Arachnoiditis

Definition

Arachnoiditis literally means "inflammation of the arachnoid," which is the middle of the three membranes (meninges) surrounding the brain and spinal cord. The term more generally refers to several rare neurologic disorders caused by inflammation of a portion of the arachnoid and subarachnoid space, affecting the neural tissue that lies beneath. Symptoms of arachnoiditis are quite variable, and may include anything from a skin rash to moderate or severe pain, to paralysis. The condition is often progressive, can only rarely be cured, and existing treatments vary in their effectiveness.

Description

Three membranes, including the dura mater, arachnoid, and pia mater, and a layer of cerebrospinal fluid (CSF) surround, protect, and cushion the brain and spinal cord. The pia mater adheres to the brain and spinal cord, and is separated from the arachnoid membrane by the subarachnoid space, which contains the circulating CSF. Arachnoiditis always involves inflammation in one or several restricted areas, but the entire membrane is never affected. Fibrous (scar) tissue growth along the affected section of the membrane usually occurs, projecting down through the subarachnoid space and encompassing neural tissue of the brain (cerebral arachnoiditis) and/or nerve roots of the spinal cord (spinal arachnoiditis). Nerve damage occurs through restricted blood flow (ischemia), compression from accumulated fluids (edema), and secondary effects of the inflammatory process itself.

Other terms used less frequently for arachnoiditis include arachnitis, chronic adhesive arachnoiditis (CAA), and spinal fibrosis. Other conditions that may be associated with or mimic arachnoiditis include syringomyelia (cyst near the spinal cord), cauda equina (lower spinal cord) syndrome, and spinal tumor. Several different types of arachnoiditis have been described, including adhesive (fibrous attachments), ossifying (bony tissue growth), neo-plastic (tumor growth), optochiasmatic (optic nerve and chiasm), and rhinosinusogenic (olfactory nerve and area above the sinuses).

Demographics

The true incidence of arachnoiditis is not known, but it is rare. It affects males and females equally, and seems to be less frequent in children than in adults. Rare cases of familial arachnoiditis have been documented, but no particular ethnic groups seem to be at higher risk.

Causes and symptoms

The causes of arachnoiditis are varied, but fall into the following four categories:

* trauma to the membrane due to spinal surgery (often multiple procedures), cranial or spinal injury, or needle insertion to remove CSF for testing
* external agents such as anesthesia, corticosteroids, medications, or medical dyes/chemicals injected near the spinal cord (epidural) or directly into the CSF
* infection of the arachnoid/CSF (meningitis)
* blood in the CSF caused by trauma, spontaneous bleeding, or infection

For reasons that are not entirely clear, different areas of the arachnoid have differing sensitivities to the causative agents. Spinal arachnoiditis due to infection most often occurs in the cervicothoracic (neck and upper back) region, while cases due to external agents most often occur in the lumbosacral (lower back) area. Likewise, spinal arachnoiditis of any type is more common than the cerebral/cranial variety.

Symptoms of cerebral arachnoiditis may include severe headaches, vision disturbances, dizziness, and nausea/vomiting. Vision disturbances are especially pronounced in optochiasmatic arachnoiditis. If inflammation and tissue growth in specific areas of the cranial arachnoid membrane divert or obstruct normal flow of the CSF, the result is hydrocephalus (increased fluid pressure within the brain).

Typical symptoms of spinal arachnoiditis include back pain that increases with activity, pain in one or both legs or feet, and sensory abnormalities of some type, usually involving decreased reflexes. Patients may also exhibit decreased range of motion of the trunk or legs, and urinary sphincter dysfunction (urgency, frequency, or incontinence). In more severe cases, partial or complete paralysis of the lower extremities may occur.

Diagnosis

The most reliable method of establishing the diagnosis of arachnoiditis is a positive computed tomography (CT) or magnetic resonance imaging (MRI) scan, combined with one or more of the symptoms. Testing for certain cell types and proteins in the CSF may prove helpful only in the early stages of the inflammation. On the other hand, imaging studies may be negative or equivocal early on, and only later be more definitive as inflammation and tissue growth becomes more pronounced. In some cases, a definitive diagnosis may not be possible.


Treatment team

A neurologist is the primary specialist involved in monitoring and treating arachnoiditis. Occupational/physical therapy (OT/PT) might also be suggested to assist with treatment for pain and adaptation to sensory deficits and/or muscular weakness in the back and lower limbs. A neurosurgeon performs any elected surgeries to address the various effects of the inflammation. Many individuals with chronic pain attend pain clinics staffed by physicians (usually anesthesiologists) and nurses who specialize in pain management. Neuropsychiatrists and neuropsychologists specialize in treating the psychological problems specific to individuals who have an underlying neurologic condition.

Treatment

Treatment for arachnoiditis is mostly done with medications, and is geared toward reducing the inflammation and alleviating pain. Medications may include both nonsteroidal and steroidal anti-inflammatory drugs, along with non-narcotic and narcotic pain medications. Other possible treatments include epidural steroid injections, transcutaneous electrical nerve stimulation (TENS), topical analgesics, and alternative medical therapies.

Direct spinal cord stimulation is a newer pain management method that involves placement of tiny electrodes under the skin, directly on the affected nerve roots near the spine. Mild current application inhibits pain signals, and is provided by a small, battery-powered unit that is placed under the skin by a surgeon.

Surgery to remove fibrous or ossified tissue at the site of the inflammation is used only if more conservative methods do not provide sufficient relief. Surgical removal of a small portion of one or more vertebrae at the area of the nerve root is called a laminectomy. A neurosurgeon treats hydrocephalus by placing a shunt (plastic tube) from the brain to the abdominal cavity to relieve increased pressure. Microsurgical techniques to remove scar tissue from around the nerve roots themselves are a more recent development.

Prognosis

Given the lack of effective treatments for arachnoiditis, the prognosis in most instances is poor, with the neurologic symptoms remaining static or worsening over time. It is not uncommon for people who undergo surgery for the condition to improve at first, but eventually regress within several years.

Resources


BOOKS

Bradley, Walter G., et al., eds. Neurology in Clinical Practice, 3rd ed. Boston: Butterworth-Heinemann, 2000.

Victor, Maurice, and Allan H. Ropper. Adam's and Victor's Principles of Neurology, 7th ed. New York: The McGraw-Hill Companies, Inc., 2001.

Wiederholt, Wigbert C. Neurology for Non-Neurologists, 4th ed. Philadelphia: W.B. Saunders Company, 2000.

PERIODICALS

Chin, Cynthia T. "Spine Imaging." Seminars in Neurology 22 (June 2002): 205–220.

Faure, Alexis, et al. "Arachnoiditis Ossificans of the Cauda Equina: Case Report and Review of the Literature." Journal of Neurosurgey/Spine 97 (September 2002): 239–243.

Rice, M. Y. K., et al. "Obstetric Epidurals and Chronic Adhesive Arachnoiditis." British Journal of Anaesthesia 92 (2004): 109–120.

Wright, Michael H., and Leann C. Denney "A Comprehensive Review of Spinal Arachnoiditis." Orthopaedic Nursing 22 (May/June 2003): 215–219.

ORGANIZATIONS

American Paraplegia Society. 75-20 Astoria Boulevard, Jackson Heights, NY 11370-1177. (718) 803-3782. .

American Syringomyelia Alliance Project, Inc. P.O. Box 1586, Longview, TX 75606-1586. 800-272-7282. .

NIH/NINDS Brain Resources and Information Network. PO Box 5801, Bethesda, MD 20824. (800) 352-9424. .

National Organization for Rare Disorders (NORD). 55 Kenosia Ave, PO Box 1968, Danbury, CT 06813-1968. (800) 999-6673; Fax: (203) 798-2291. .

National Spinal Cord Injury Association. 6701 Democracy, Bethesda, MD 20817. (800) 962-9629. .

Spinal Cord Society. 19051 County Hwy 1, Fergus Falls, MN 56537. (218) 739-5252.

Autonomic dysfunction

Definition

Dysfunction of the autonomic nervous system (ANS) is known as dysautonomia. The autonomic nervous system regulates unconscious body functions, including heart rate, blood pressure, temperature regulation, gastrointestinal secretion, and metabolic and endocrine responses to stress such as the "fight or flight" syndrome. As regulating these functions involves various and multiple organ systems, dysfunctions of the autonomic nervous systems encompass various and multiple disorders.


Description

The autonomic nervous system consists of three subsystems: the sympathetic nervous system, the parasympathetic nervous system and the enteric nervous system. The ANS regulates the activities of cardiac muscle, smooth muscle, endocrine glands, and exocrine glands. The autonomic nervous system functions involuntarily (reflexively) in an automatic manner without conscious control.

In contrast to the somatic nervous system that always acts to excite muscles groups, the autonomic nervous systems can act to excite or inhibit innervated tissue. The ANS achieves this ability to excite or inhibit activity via a dual innervation of target tissues and organs. Most target organs and tissues are innervated by neural fibers from both the parasympathetic and sympathetic systems. The systems can act to stimulate organs and tissues in opposite ways (antagonistic). For example, parasympathetic stimulation acts to decrease heart rate. In contrast, sympathetic stimulation results in increased heart rate. The systems can also act in concert to stimulate activity. The autonomic nervous system achieves this control via two divisions: the sympathetic nervous system and the parasympathetic nervous system. Dysfunctions of the autonomic nervous system are recognized by the symptoms that result from failure of the sympathetic or parasympathetic components of the ANS.

Primary dysautonomias include multiple system atrophy (MSA) and familial dysautonomia. The dysfunction can be extensive and manifest as a general autonomic failure or can be confined to a more localized reflex dysfunction.

With multiple system atrophy, a generalized autonomic failure, male patients experience urinary retention or incontinence and impotence (an inability to achieve or maintain a penile erection). Both males and females experience ataxia (lack of muscle coordination) and a dramatic decline in blood pressure when they attempt to stand (orthostatic hypotension). Symptoms similar to Parkinson's disease may develop, such as slow movement, tremors, and stiff muscles. Visual disturbances, sleep disturbances, and decreased sweating may also occur.

Persons with autonomic dysfunction who do not exhibit the classical symptoms of orthostatic hypotension may exhibit a less dramatic dysfunction termed orthostatic intolerance. These patients experience a milder fall in blood pressure when attempting to stand. However, because the patients have an increased heart rate when standing, they are described as having postural tachycardia syndrome (POTS).

Although not as prevalent in the general population as hypertension, orthostatic intolerance is the second most common disorder of blood pressure regulation and is the most prevalent autonomic dysfunction. Orthostatic hypotension and orthostatic intolerance can result in a wide array of disabilities. Common orthostatic intolerance syndromes include: hyperadrenergic orthostatic hypotension (partial dysautonomia); orthostatic tachycardia syndrome (sympathicotonic orthostatic hypotension); postural orthostatic tachycardia syndrome (mitral valve prolapse syndrome); postural tachycardia syndrome (soldier's heart); hyperadrenergic postural hypotension (vasoregulatory asthenia); sympathotonic orthostatic hypotension (neurocirculatory asthenia); hyperdynamic beta-adrenergic state (irritable heart syndrome); and idiopathic hypovolemia (orthostatic anemia).

Demographics

Milder forms of autonomic dysfunction such as orthostatic intolerance affect an estimated 500,000 people in the United States. Orthostatic intolerance more frequently affects women; female-to-male ratio is at least 4:1. It is most common in people less than 35 years of age. More severe forms of dysautonomia such as multiple system atrophy often occur later in life (average age of onset 60 years) and affect men four times as often as women.

Causes and symptoms

Symptoms of the autonomic dysfunction of orthostatic intolerance include lightheadedness, palpitations, weakness, and tremors when attempting to assume an upright posture. Less frequently, patients experience visual disturbances, throbbing headaches, and often complain of fatigue and poor concentration. Some patients report fainting when attempting to stand.

The cause of lightheadedness, fainting, and similar symptoms is a lack of adequate blood pressure in the cerebral circulatory system.

In addition to orthostatic hypotension and Parkinson-type symptoms, persons with multiple systems atrophy may have difficulty articulating speech, sleep apnea and snoring, pain in the back of the neck, and fatigue. Eventually, cognitive (mental reasoning) ability declines in about 20% of cases. Multiple systems atrophy occurs sporadically and the cause is unknown.

Diagnosis

Diagnosis of orthostatic intolerance is made when a patient experiences a decrease of blood pressure (not exceeding 20/10 mm Hg) when attempting to stand and a heart rate increase of less than 30 beats per minute.

Diagnosis of other types of dysautonomia is difficult, as the disorders are varied and mimic other diseases of the nervous system. As Parkinsonism is the most frequent motor deficit seen in multiple systems atrophy, it is often misdiagnosed as Parkinson's disease. Magnetic resonance imaging (MRI) of the brain can sometimes detect abnormalities of striatum, cerebellum, and brainstem associated with multiple systems atrophy. But in up to 20% of MSA patients, MRI of the brain is normal. A test with the drug clonidine has also been used to differentiate Parkinson's disease from multiple systems atrophy, as certain hormone levels in the blood will increase in persons with Parkinson's disease after clonidine administration, but not in persons with multiple systems atrophy. Symptoms such as severe dysarthria (difficulty articulating speech) and stridor (noisy inspiration) alert the physician to the possibility of multiple systems atrophy, as they occur in the disorder, but are rare in Parkinson's disease.

Treatment team

Caring for a person with a disorder of the autonomic nervous system requires a network of health professionals, community resources, and friends or family members. A neurologist usually makes the diagnosis, and the neurologist and primary physician coordinate ongoing treatment and symptom relief. Physical, occupational, speech, and respiratory therapists provide specialized care, as do nurses. Social service and mental health consultants organize support services.

Treatment

At present there is no cure for severe autonomic dysfunction. Treatment is centered on the remediation of symptoms, patient support, and the treatment of underlying diseases and disorders in cases of secondary autonomic dysfunction. In many cases, cure or an improvement in the underlying disease or disorder improves the patient prognosis with regard to remediation of autonomic dysfunction symptoms.

With regard to orthostatic hypotension, drug treatment includes fludrocortisone, ephedrine, or midodrine. Medications are accompanied by postural relief such as elevation of the bed at the head and by dietary modifications to provide some relief for the symptoms of dizziness and tunnel vision.

In multiple systems atrophy, anti-Parkinson medications such as Sinemet often help with some of the symptoms of muscle rigidity and tremor, and create an overall feeling of well-being. Medications used in the treatment of orthostatic hypotension tend to not perform as well in this group; although they elevate the blood pressure while standing, they decrease the blood pressure while reclining.

Recovery and rehabilitation

Recovery from some dysautonomias can be complicated by secondary conditions such as alcoholism, diabetes, or Parkinson's disease. Some conditions improve with treatment of the underlying disease, while only halting of the progression of symptoms is accomplished in others. Some mild dysautonomias stabilize and, with treatment, cause few limitations to daily activities.

Overall, as there are no cures for most severe or progressive dysautonomias, the emphasis is instead placed upon maintaining mobility and function for as long as possible. Aids for walking and reaching, positioning devices, and strategies for maintaining posture, balance, and blood pressure while rising can be provided by physical and occupational therapists. Speech and nutritional therapists can devise diets and safe strategies for eating, and recommend tube feedings if necessary.

Clinical trials

As of mid-2004, the Mount Sinai Medical Center in New York was recruiting participants for a study related to a new drug for the treatment of multiple systems atrophy. Persons interested in participating in the study (Droxidopa in Treating Patients With Neurogenic Hypotension) should contact the study recruiting coordinator Horacio Kaufmann at telephone: (212) 241-7315. Additional trials for the study and treatment of multiple systems atrophy and other dysautonomias can be found at the National Institutes of Health website for clinical trials: .

Prognosis

The prognosis for persons suffering autonomic dysfunction is variable and depends on specific dysfunction and on the severity of the dysfunction. Autonomic dysfunctions can present as acute and reversible syndromes, or can present in more chronic and progressive forms. Persons with orthostatic intolerance can usually maintain a normal lifespan and active lifestyle with treatment and minimal coping measures, while persons with multiple systems atrophy usually have a lifespan of about 5–7 years after diagnosis.

BOOKS

Goldstein, David S., and Linda J. Smith. The NDRF Handbook for Patients with Dysautonomias. Malden, MA: Blackwell Futura Media, 2002.

OTHER

"Disorders of the Autonomic Nervous System." National Dysautonomia Research Foundation. May 16, 2004 (May 22, 2004). .

"NINDS Dysautonomia Information Page." National Institute of Neurological Disorders and Stroke. May 16, 2004 (May 22, 2004). .

ORGANIZATIONS

Dysautonomia Foundation. 633 Third Avenue, 12th Floor, New York, NY 10017-6706. (212) 949-6644; Fax: (212) 682-7625. info@familialdysautonomia.org.

Familial Dysautonomia Hope Foundation, Inc. (FD Hope). 1170 Green Knolls Drive, Buffalo Grove, IL 60089. (828) 466-1678. info@fdhope.org.

National Dysautonomia Research Foundation. 1407 West 4th Street, Red Wing, MN 55066-2108. (651) 267-0525; Fax: (651) 267-0524. ndrf@ndrf.org.

National Organization for Rare Disorders (NORD). P.O. Box 1968 (55 Kenosia Avenue), Danbury, CT 06813-1968. (203) 744-0100 or (800) 999-NORD; Fax: (203) 798-2291. orphan@rarediseases.org.

Shy-Drager/Multiple System Atrophy Support Group, Inc. 2004 Howard Lane, Austin, TX 78728. (866) 737-4999 or (800) 999-NORD; Fax: (512) 251-3315. Don.Summers@shy-drager.com.

Acute disseminated encephalomyelitis

Definition

Acute disseminated encephalomyelitis (ADE) is a neurological disorder involving inflammation of the brain and spinal cord. A hallmark of the disorder is damage to the myelin sheath that surrounds the nerve fibers in the brain, which results in the inflammation.
Description

Acute disseminating encephalomyelitis was first described in the mid-eighteenth century. The English physician who first described the disorder noted its association with people who had recently recovered from smallpox. Symptoms often develop without warning. As well, mental disorientation can occur. The disorder is also known as postinfectious encephalomyelitis and immune-mediated encephalomyelitis. The nerve demyelination that occurs in ADE also occurs in multiple sclerosis. However, the two maladies differ in that multiple sclerosis is long lasting and can recur over time, while ADE has a monophasic course, meaning that once it is over, further attacks rarely occur.
Demographics

ADE can occur in both children and adults, although it occurs more commonly in children. ADE is not rare, accounting for approximately 30% of all cases of encephalitis (brain inflammation).
Causes and symptoms

Acute disseminating encephalomyelitis can occur as a consequence of a bacterial or viral infection (including HIV), following recovery from infection with the malarial protozoan, or as a side effect of vaccination or another inoculation. ADE is usually a consequence of a viral illness, and occurs most often after measles, followed by rubella, chicken pox, Epstein-Barr, mumps and pertussis (whooping cough). Typically, symptoms appear two to three weeks after the precipitating infection or immunization. Alternatively, ADE may develop with no known associations.

Despite the different causes, the symptoms that develop are similar. A number of non-specific symptoms, which vary from one person to another, include headache, stiff neck, fever, vomiting, and weight loss. These symptoms are quickly followed by lethargic behavior, seizures, hallucinations, sight difficulties, and even coma. Paralysis can occur in an arm or leg (monoparesis) or along an entire side of the body (hemiplegia).

These symptoms can last a few weeks to a month. In some people, symptoms can progress from the appearance of symptoms to coma and death in only a few days. Brain damage is largely confined to the white matter. Microscopic examination will typically reveal invasion of white blood cells into small veins. The nerve myelin damage occurs in the regions where the white blood cells accumulate. Examination of the brains of patients who have died of the disorder has not yielded consistent results. Some brains appear normal, while others display the nerve damage and white blood cell congestion.

Diagnosis

Diagnosis is made based on the above symptoms and the patient's medical history (i.e., recent infection or vaccination). In the early stages of the disorder, diagnosis can be confused with diseases including acute meningitis, acute viral encephalitis, and multiple sclerosis. Often, the latter can be ruled out using magnetic resonance imaging (MRI) and examination of the cerebrospinal fluid (CSF). Typically, in acute disseminating encephalomyelitis, CSF contains abnormally elevated levels of white blood cells and protein; and magnetic resonance imaging can reveal brain alterations.


Treatment team

The treatment team typically consists of a primary care physician and, when hospitalization is necessary, nurses and specialized medical care personnel.

Treatment

Corticosteroid medication is often prescribed in order to lessen the nerve inflammation. Use of high doses of steroids can often produce a rapid diminishing of the symptoms. Other kinds of treatment depend on the nature of the symptoms that develop. Supportive care includes keeping a patient comfortable and hydrated.

Recovery and rehabilitation

Persons recovering from acute disseminated encephalomyelitis need time to recover their normal consciousness and movements. Problems with memory, especially short-term memory, may be present. The recovering person sometimes has trouble controlling their emotions and is easily frustrated. Frequent periods of rest, alternating with shorter periods of mental and physical exercise are prescribed during initial recovery. The maximum possible recovery of brain and motor function may take a period of weeks or months.
Clinical trials

There are no clinical trials for the study of ADE recruiting patients or being planned in the United States, as of January 2004. However, organizations such as the National Institute for Neurological Disorders and Stroke undertake and fund studies on disorders that involve damage to the myelin sheath of nerve cells. By understanding the nature of the disorders, it is hoped that detection can be improved and strategies will evolve to prevent or reverse the nerve damage.
Prognosis

Prognosis varies from person to person. Some patients may recover fully, with no residual effects. Others may have some residual damage. Seldomly, ADE is fatal. Early detection and treatment improves a patient's outlook.

Special concerns

Although the incidence of ADE occurring after vaccination is rare, in recent years, public debate has led some parents to choose that their children not receive the recommended childhood vaccinations. The American Academy of Pediatrics asserts that, despite concerns about vaccine safety, vaccination is far safer than accepting the risks for the diseases that the vaccines prevent.


Resources


BOOKS

Icon Health Publications. The Official Patient's Sourcebook on Acute Disseminated Encephalomyelitis: A Revised and Updated Directory for the Internet Age. San Diego: Icon Group International, 2002.

PERIODICALS

Anlar, B., C. Basaran, G. Kose, A. Guven, S. Haspolat, A. Yakut, A. Serdaroglu, N. Senbil, H. Tan, E. Karaagaoglu, and K. Oguz. "Acute disseminated encephalomyelitis in children: outcome and prognosis." Neuropediatrics (August 2003): 194–199.

Brass, S. D., Z. Caramanos, C. Santos, M. E. Dilenge, Y. Lapierre, and B. Rosenblatt. "Multiple sclerosis vs acute disseminated encephalomyelitis in childhood." Pediatric Neurology (September 2003): 227–231.

Koibuchi, T., T. Nakamura, T. Miura, T. Endo, H. Nakamura, T. Takahashi, H. S. Kim, Y. Wataya, K. Washizaki, K. Yoshikawa, and A. Iwamoto. "Acute disseminated encephalomyelitis following Plasmodium vivax malaria." Journal of Infection and Chemotherapy (September 2003): 254–256.

Narciso, P., S. Galgani, B. Del Grosso, M. De Marco, A. De Santis, P. Balestra, V. Ciapparoni, and V. Tozzi. "Acute disseminated encephalomyelitis as manifestation of primary HIV infection." Neurology (November 2001): 1493–1496.

OTHER

"Acute Disseminated Encephalomyelitis Information Page." National Institute of Neurological Disorders and Stroke. (January 26, 2004).

ORGANIZATIONS

National Institute for Neurological Diseases and Stroke (NINDS). 6001 Executive Boulevard, Bethesda, MD 20892. (301) 496-5751 or (800) 352-9424. .

National Organization for Rare Disorders. 55 Kenosia Avenue, Danbury, CT 06813-1968. (203) 744-0100 or (800) 999-6673; Fax: (203) 798-2291. .

Brian Douglas Hoyle, PhD

Postoperative Pain in Neurosurgery: A Pilot Study in Brain Surgery.

Clinical Studies

Neurosurgery. 38(3):466-470, March 1996.
De Benedittis, Giuseppe M.D.; Lorenzetti, Ariberto M.D.; Migliore, Matteo M.D.; Spagnoli, Diego M.D.; Tiberio, Francesca M.D.; Villani, Roberto M. M.D.

Abstract:
THE INCIDENCE, MAGNITUDE, and duration of acute pain experienced by neurosurgical patients after various brain operations are not precisely known, because of a lack of well-designed clinical and epidemiological studies. We assessed these important pain variables in 37 consecutive patients who underwent various brain neurosurgical procedures. Postoperative pain was more common than generally assumed (60%). In two-thirds of the patients with postoperative pain, the intensity was moderate to severe. Pain most frequently occurred within the first 48 hours after surgery, but a significant number of patients endured pain for longer periods. Pain was predominantly superficial(86%), suggesting somatic rather than visceral origin and possibly involving pericranial muscles and soft tissues. Subtemporal and suboccipital surgical routes yielded the highest incidence of postoperative pain. Age and sex were significantly associated with the onset of pain, with female and younger patients reporting higher percentages of postoperative pain. Psychological Minnesota Multiphasic Personality Inventory profiles of patients with and without pain significantly differed on the Hypochondriasis scale, with patients without pain scoring unexpectedly higher than patients with pain. It is possible that hypochondriasis serves as a defense mechanism against pain, at least in some patients. Results of this pilot study indicate that postoperative pain after brain surgery is an important, although neglected, clinical problem, that deserves greater attention by surgical teams, to provide better and more appropriate treatment.

Copyright (C) by the Congress of Neurological Surgeons

Endoscope-assisted Brain Surgery: Basic Concept, and Current Technique.

Special Technical Article

Neurosurgery. 42(2):219-224, February 1998.
Perneczky, Axel MD; Fries, Georg MD

Abstract:
RATIONALE: The evolution of neurosurgical techniques indicates the effort to reduce surgery-related traumatization of patients. The reduction of traumatization contributes to better postoperative outcomes. The improvement of diagnostic imaging techniques facilitates not only the precise localization of lesions but also the accurate determination of topographical relations of specific lesions to individual anatomic variations of intracranial structures. This precision of diagnostic imaging should be used to perform individual surgical procedures through so-called keyhole approaches. Keyhole craniotomies are afflicted with a reduction of light intensity in the depth of the operating field, and they provide rather narrow viewing angles. Thus, objects located directly opposite the approach entrance are more visible than those in the shadow of the microscope beam. These two deficiencies of keyhole craniotomies can be compensated for by the intraoperative use of rigid rod lens endoscopes, the shaft of which remains easily controllable through the surgical microscope.

CONCEPT: Endoscope-assisted microsurgery, like all routine microsurgical procedures, is performed with both hands; the endoscope is fixed in its desired position via a mechanical arm to the headholder. Because of their superior optical quality and maneuverability, only rigid lens scopes are used for endoscope-assisted brain microsurgery. There are five ways of observing the endoscopic and microscopic images at the same time: 1) observation of the microscopic image through the oculars of the microscope and observation of the endoscopic image on a video screen placed in front of the surgeon, 2) observation of the microscopic image through the oculars of the microscope and display of the endoscopic image on a head-mounted LCD screen, 3) projection of both microscopic and endoscopic images on one screen in a picture-in-picture mode, 4) projection of both microscopic and endoscopic images into specially designed microscope oculars, and 5) transmission of both microscopic and endoscopic images into a head-mounted LCD screen.

DISCUSSION: With the knowledge of almost all individual anatomic and pathoanatomic details of a specific patient, it is possible to target the individual lesion through a keyhole approach using the particular anatomic windows. As the light intensity and the depiction of important anatomic details are improved by the intraoperative use of lens scopes, endoscope-assisted microsurgery during keyhole approaches may provide maximum efficiency to remove the lesion, maximum safety for the patient, and minimum invasiveness.

Endoscope-assisted Brain Surgery: Part 2-Analysis of 380 Procedures.

Clinical Studies

Neurosurgery. 42(2):226-231, February 1998.
Fries, Georg MD; Perneczky, Axel MD

Abstract:
OBJECTIVES: Microsurgical techniques and instruments that help to reduce intraoperative retraction of normal intracranial neuronal and vascular structures contribute to improved postoperative results. To achieve sufficient control of the operating field without retraction of neurovascular components, the resection of dura and bone edges is frequently required, which, on the other hand, increases operating time and operation-related trauma. The use of endoscopes may help to reduce retraction and, at the same time, may help to avoid additional dura and bone resection. The aim of this study is to describe the principles on which the technique of endoscope-assisted brain surgery is based, to give an impression of possible indications for endoscope-assisted microsurgical procedures, and, with illustrative cases, to delineate the advantages of endoscopes used as surgical instruments during microsurgical approaches to intracranial lesions.

METHODS: During a period of 4.5 years, 380 microsurgical procedures were performed as endoscope-assisted microneurosurgical operations. This surgical series was analyzed for time of surgery, usefulness of intraoperative endoscopy, and complication rates. Lens scopes with viewing angles of 0 to 110 degrees and with diameters of 2.0 to 5.0 mm as well as newly designed "viewing dissectors" (curved, rigid fiberscopes) with diameters of 1.0 to 1.5 mm connected to a video unit were used as microsurgical instruments. The positioning of the endoscopes was achieved by retractor arms fixed to the Mayfield headholder. Thus, the surgeon was able to perform customary microsurgical manipulations with both hands under simultaneous endoscopic and microscopic control.

RESULTS: The lesions treated with endoscope-assisted microsurgery comprised 205 tumors, 53 aneurysms, 86 cysts, and 36 neurovascular compression syndromes. Eighty-nine of these lesions were localized in the ventricular system, 242 in the subarachnoid space or intracerebral, and 49 in the sella. Endoscope-assisted microsurgery was advantageous to reduce the size and the operation-related tissue trauma of approaches to lesions within the ventricular system, in the brain tissue as well as in the subarachnoid space at the base of the brain. Using less retraction during tumor removal, the visual control of retrosellar, endosellar, retroclival, and infratentorial structures was improved. Video-endoscope instrumentation was especially helpful during procedures in the posterior cranial fossa and at the craniocervical junction. It allowed for inspection of channels and hidden structures (e.g., the internal auditory meatus, the ventral surface of the brain stem, the ventral aspect of root entry zones of cranial nerves, the content of the foramen magnum, and the upper cervical canal), both without retraction and without resection of dura and bone edges. Endoscope instrumentation during surgery for large or giant aneurysms was useful to dissect perforators on the back side of the aneurysms and to control the completeness of clipping.

CONCLUSION: Although the results reported herein cannot be compared directly with those of exclusive microsurgical procedures performed during the same period of time, videoendoscope-assisted microsurgery can be recommended as a time-saving, trauma-reducing procedure apt to improve postoperative outcomes.

Copyright (C) by the Congress of Neurological Surgeons

Ventriculomegaly, isolated

Gianluigi Pilu, MD

Synonyms: ventriculomegaly, hydrocephalus, acqueductal stenosis, communicating hydrocephalus

Definition: overt enlargement of the lateral ventricles (atrial width > 15 mm) in the absence of other sonographically demonstrable central nervous system anomalies.

Prevalence: The incidence of congenital cerebral lateral ventriculomegaly ranges between 0.3 to 1.5 in 1000 births in different series.Isolated ventriculomegaly accounts for 30%-60% of fetuses with enlarged lateral cerebral ventricles.

Pathogenesis: In the majority of cases, isolated cerebral lateral ventriculomegaly is the consequence of an obstruction along the normal pathway of the cerebrospinal fluid (obstructive hydrocephalus).

Etiology: Congenital ventriculomegaly is a heterogeneous disease for which genetic, infectious, teratogenic and neoplastic causes have been implicated. A multifactorial pattern of inheritance is probably responsible for most cases of congenital hydrocephalus. X-linked hydrocephalus comprises approximately 5% of all cases. This condition is caused by mutations in the gene at Xq28 encoding for L1, a neural cell adhesion molecule. Mutations in this gene are also responsible for other syndromes with clinical overlap that are frequently referred to as the X-linked hydrocephalus spectrum and include MASA (mental retardation, aphasia, shuffling gait, adducted thumbs), complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum. Infections implicated in the determination of congenital ventriculomegaly include toxoplasmosis, syphilis, cytomegalovirus, mumps and influenza virus.

Pathology: Overt lateral ventriculomegaly can result from different pathological entities. Fetuses with isolated ventriculomegaly diagnosed in utero at our institution were usually found at birth to have either aqueductal stenosis or communicating ventriculomegaly. Progression from communicating ventriculomegaly to aqueductal stenosis has been documented and it is uncertain whether these two conditions are separate clinical entities. Communicating hydrocephalus may however derive from acute events such as subarachnoid hemorrhage, or be caused by overproduction of cerebro-spinal fluid by a choroid plexus papilloma. The degree of ventricular enlargement is variable. Knowledge about the pathogenesis of congenital ventriculomegaly is largely incomplete. Thinning of the cortex, macrocrania and symptoms of intracranial hypertension are frequently found. Studies performed in experimental animals and based on biopsies of brain tissue obtained in children at the time of shunting seem to demonstrate the following sequence of events: initially there is disruption of the ependymal lining, followed by edema of the white matter. This phase has been considered reversible. Later, there is proliferation of astrocytes and fibrosis of the white matter. The gray matter seems to be spared during the initial staged of the process.

Recurrence risk: apart from X-linked hydrocephalus (recurrence risk 50% of males) congenital ventriculomegaly is mostly multifactorial. Couples with a previously affected child have a recurrence risk of 4%.

Associated anomalies: extra-cranial abnormalities occur in 30% of cases. Chromosomal aberrations are found in 11% of cases (6% of fetuses with ventriculomegaly as the only antenatal finding, 25% of cases with multiple anomalies). The X-linked hydrocephalus spectrum is frequently associated with abduction of the thumbs, abnormal facies and absence of the septum pellucidum.

Diagnosis: Different approaches have been proposed for the diagnosis of fetal lateral cerebral ventriculomegaly. A qualitative approach has been suggested. Under normal condition, the large fetal choroid plexus entirely fills the cavity of the lateral ventricle at the level of the atria, being closely apposed to both the medial and the lateral wall, irrespective of gestational age. In even early stages of ventriculomegaly, the choroid plexus is shrunken anteriorly displaced, thus being clearly detached from the medial wall (Figure 1). However, in a finite number of normal fetuses some disproportion between the choroid plexus and the atrial lumen is found. Normal values for virtually all portions of the lateral ventricles throughout gestation are available. Measurement of the width of atrium is however favored. Between 15 and 40 weeks’ gestation, the mean value is consistently about 7 mm and the standard deviation about 1 mm in most studies. Some degree of asymmetry of the lateral ventricles exists in human fetal brain and is detectable in utero.] A measurement of less than 10 mm is indicative of normalcy. Overt lateral cerebral ventriculomegaly is defined as a measurement of 15 mm or more. Sonographic demonstration of abducted thumbs in combination with ventriculomegaly and other intracranial abnormalities should prompt the diagnosis of X-linked hydrocephalus spectrum.

Figure 1: Fetal hydrocephalus: gross enlargement of the lateral ventricles, thinning of the cortex, asymmetric choroid plexuses.

Differential diagnosis: The main problem is distinguishing isolated ventriculomegaly from more complex abnormalities of the fetal brain that have frequently a different prognosis (e.g. holoprosencephaly, porencephaly, etc). We recommend careful multiplanar examination of the fetal brain, performed if possible with a high-resolution vaginal probe, and a detailed evaluation of the spine.

Implications for targeted examinations: For patients at risk for fetal cerebral ventriculomegaly (e.g. because of a previously affected child, or because of TORCH infection), we recommend multiplanar examination of the fetal brain, performed if possible with a high-resolution vaginal probe, including visualization and assessment of both lateral ventricle. It has been our experience, and it has been reported in a handful of cases that ventriculomegaly may develop only in late gestation or after birth, particularly with the X-linked hydrocephalus spectrum. The patients at risk for should be informed that a normal midtrimester sonogram does not rule out this condition. Couples with a previously affected child should receive genetic counseling, because sometimes a generic diagnosis of congenital hydrocephalus may hinder a more complex anomaly with significant genetic implications. For example, patients at risk for X-linked hydrocephalus spectrum should be offered DNA analysis, as the recurrence rate is high and midtrimester sonography is frequently unsuccessful.

Implications for sonographic screening: In all standard sonographic examinations, a view of the lateral ventricles should be obtained, and at least one of the atria should be visualized and assessed. A qualitative evaluation is acceptable, and the presence of the choroid plexus filling the cavity of the atrium, being closely apposed to both the medial and lateral wall of the ventricle, is indicative of normalcy. A quantitative approach is however favored, and a measurement less than 10 mm is considered normal between 15-40 weeks. Congenital ventriculomegaly may develop late in gestation, and a normal midtrimester exam does not exclude this condition.

Prognosis: In a recent review, isolated ventriculomegaly diagnosed in utero was associated with a postnatal survival rate of 70% and 59% of the survivors had normal developmental quotient at follow-up. These results may be biased however by the inclusion of cases with borderline enlargement of the ventricles. In one of the largest pediatric series, excluding cases with X-linked hydrocephalus and congenital toxoplasmosis, the survival rate was 62% at 10 years, and 50% of survivors had a low developmental quotient (< 60). Only 29% of infants attending school reached a normal academic level. Macrocrania at birth, ventricular size and age at surgery had no influence on the outcome. X-linked hydrocephalus spectrum carries a severe prognosis, being usually associated with severe neurological deficits and premature death.

Obstetrical management: A search for associated congenital anomalies, including fetal karyotyping) and a workup for congenital infections associated with hydrocephalus (i.e., toxoplasmosis, cytomegalovirus, rubella) is indicated. Before viability, the option of pregnancy termination should be offered to the parents. Little data exist to support any specific manage­ment plan in continuing pregnancies. There is no evidence that anticipation of delivery is beneficial. Most infants with ventriculomegaly do not have macrocrania, and therefore a trial of labor is indicated in vertex presen­tation. Cesarean section should be reserved for standard obstetrical indications. Whether cephalocentesis should be offered in cases with macrocrania to overcome cephalo-pelvic disproportion is debated. Cephalocentesis is indeed associated with a perinatal mortal­ity in excess of 90 percent. Intrauterine treatment consist­ing of the implantation of a ventriculoamniotic shunt for the relief of intracranial pressure during gestation has been attempted. Although experience in ani­mal models appears encouraging, the clinical appli­cation of these procedures remains undetermined. In a group of 39 treated fetuses, the perinatal mortality rate was 18 percent, and moderate to severe handicaps affected 66 percent of the survivors.

taken from here

Recovering from brain surgery

After any surgery, it is not unusual, at first, to feel worse than you did before. This can be depressing if you are not prepared for it. You have just had brain surgery. That is a lot for your body to cope with. The post-op swelling means it will be a while before you feel the benefit from having had your tumor removed.

After brain surgery, it is not uncommon to have dizzy spells or to get confused about where you are and what is happening to you from time to time. These episodes can come and go. They can be upsetting for your relatives and also for you. Your nurse and doctor will explain that this is normal and part of the recovery period.

The operation itself can often make your symptoms worse at first. Or you may notice symptoms that you didn’t have before. The swelling can cause

* Weakness
* Poor balance or lack of coordination
* Personality changes
* Speech problems
* Fits

This time can be particularly difficult for your loved ones. They may worry that your operation has not worked. But the symptoms will usually lessen and disappear as you recover. This may take only days. But it can take weeks or sometimes months.

Your surgeon will have given you some idea of what to expect in the way of recovery. For some people, recovery will be complete. You may be able to get back to the same fitness level you had before your tumour. And may be able to return to all your usual activities before long, including your job if you have one.

If you have long term problems

Because of the position of their tumour, some people have long-term problems with speech or with weakness of an arm or leg. This can take a long time to recover from. It may be hard for you to keep your spirits up through this time. But with effort and help from physiotherapists, speech therapists and other rehabilitation specialists, you will get a lot better.

Your rehabilitation will start as soon as you can get out of bed. You will gradually be able to do more and more for yourself. You may never quite recover to the same level of fitness as before your treatment. But your condition can and will improve to some extent. Your confidence will increase as you learn to manage with whatever level of disability you have to cope with. There is more about recovering after a brain tumour in the Living with a brain tumour section.

How Are Brain and Spinal Cord Tumors in Children Treated?

Children with central nervous system tumors may be treated by surgery, radiation therapy, and/or chemotherapy. Treatment is different for different kinds of tumors. Each child's treatment must be approached individually to give the child the best chance of cure. Long-term side effects of the treatment must also be considered. Because of this, children under 3 years old are usually not given radiation therapy. Instead, the treatment relies mainly on removing the tumor by surgery and chemotherapy.

This approach is based on the desire to delay the need for radiation therapy, which can cause developmental delay and problems with intellectual development. Even in older children, however, radiation treatment can cause problems. Radiation oncologists (doctors specializing in treatment of tumors with radiation) try very hard to limit the amount of normal brain tissue that they treat.

The Key Statistics About Brain and Spinal Cord Cancers

Malignant brain and spinal cord tumors, the second most common cancers in children (after leukemia), account for about 17% of malignant tumors. Around 3,200 central nervous system tumors are diagnosed each year in children under the age of 20. About one fourth of these are considered benign tumors. The incidence (number per 100,000 children) of these cancers has not changed much in recent years.

Over one half of patients with childhood brain tumors (all types combined) survive longer than 5 years. The outlook varies according to the type and location of the tumor. For example, approximately 90% of astrocytomas of the cerebellum are cured by surgery.

Brain and Spinal Cord Tumors in Children

Brain tumors are masses of abnormal cells that have grown out-of-control. In most other parts of the body, it is critically important to distinguish benign (noncancerous) tumors from malignant (cancerous) ones. Benign tumors are almost never life threatening. The main reason cancers are so dangerous is because they can spread throughout the body. Most brain cancers can spread through the brain tissue but rarely spread to other areas of the body. Even so-called “benign” tumors are can, as they grow, compress brain tissue, causing damage that is often disabling and sometimes fatal. For this reason, doctors usually speak of "brain tumors" rather than "brain cancers." The major distinction is how readily they spread through the rest of the brain central nervous system and whether they can be removed and not come back.

The central nervous system is the medical name for the brain and spinal cord. Central nervous system tumors of adults and children often form in different areas, develop from different cell types, and may have a different outlook and treatment. This document refers to children's tumors.

The brain is the center of thought, feeling, memory, speech, vision, hearing, movement, and much more. The spinal cord and special nerves in the head called cranial nerves carry messages between the brain and the rest of the body. These messages tell our muscles how to move, transmit information gathered by our senses, and help coordinate our internal organs. The brain is located within and protected by the skull. Likewise, the spinal cord is protected by the bones of the spinal column. The brain and spinal cord are surrounded and cushioned by a special fluid, called cerebrospinal fluid. Cerebrospinal fluid is produced by the choroid plexus, which is located in cavities within the brain called ventricles. The ventricles as well as the spaces around the brain and spinal cord are filled with cerebrospinal fluid.

Parts of the Brain and Spinal Cord

The brain and spinal cord are the 2 main parts of the central nervous system.

The main areas of the brain include the cerebral hemispheres, cerebellum, and brain stem. Each of these parts has a special purpose. Tumors of different parts of the central nervous system disrupt different functions and cause different symptoms. Any disease involving that particular location within the brain can cause these symptoms, and they do not necessarily mean a brain tumor is present. Also, tumors in different areas of the central nervous system may be treated differently and have a different prognosis (outlook for survival). In very young children, less than 3 years of age, itÂ’s often hard to tell which part of the brain is affected during its early development. Very young children may not have the usual symptomns coming from that part of the brain involved as would be seen in adults. In this age group the only symptoms may be nonspecific and include irritability, crying, poor feeding, or vomiting.

The 2 cerebral hemispheres control reasoning, thought, emotion, and language. They are also responsible for your planned muscle movements (throwing a ball, walking, chewing, etc.) and for taking in sensory information such as vision, hearing, smell, touch, and pain.

The symptoms caused by a tumor in a cerebral hemisphere depend on the part of the hemisphere in which the tumor arises. Common symptoms include:

* seizures
* trouble speaking
* a change of mood such as depression
* a change in personality
* numbness, weakness or paralysis of part of the body
* changes in vision, hearing, and sensation

The cerebellum controls coordination of movement. Tumors of the cerebellum cause difficulty with coordination in walking, difficulty with fine movements of arms and legs, and changes in rhythm of speech.

The brain stem contains bundles of very long nerve fibers (axons) that carry signals controlling muscles and sensation or feeling from the cerebrum to and from the rest the body. In addition, most cranial nerves (which carry signals to and from the face, eyes, tongue, and mouth) start in the brain stem. Special centers in the brain stem also control breathing and the beating of the heart.

Tumors in this critical area of the brain may cause weakness, stiff muscles, or problems with sensation, hearing, facial movement, and swallowing. Double vision is a common early symptom of brain stem tumors, as are problems with coordination in walking. Because tumors of the brain stem often intermingle with normal nerve cells and the brain stem is so essential for life, it may not be possible to surgically remove these tumors from the brain stem.

The spinal cord, like the brain stem, contains bundles of very long axons (wire-like extensions) that carry signals controlling muscles, sensation or feeling, and bladder and bowel control. Spinal cord tumors may cause weakness, paralysis, or numbness. Because the spinal cord is such a narrow structure, tumors arising within it usually cause symptoms involving both sides of the body (for example, weakness or numbness of both legs). This is different than tumors of the brain, which usually affect only one side of the body. Moreover, most tumors of the spinal cord arise below the neck after nerves to the arms have branched off the spinal cord, so that only lower body functions – bowel, bladder, or leg – are affected.

Tumors may also arise from cranial nerves. The most common cranial nerve tumor in children is optic glioma, a tumor of the optic nerve (the optic nerve is actually an extension of brain tissue to the eye) causing blindness. Tumors arising from other cranial nerves may cause hearing loss (acoustic nerve) in one or both ears, facial paralysis (facial nerve), or facial numbness or pain (trigeminal nerve). Tumors arising in the nerves of the peripheral nervous system (parts of the nervous system other than the brain and spinal cord) generally cause pain, weakness,and/or loss of sensation in the area served by that nerve. They can also weaken the muscles controlled by that nerve.

Types of Cells and Tissues in the Brain and Spinal Cord

The brain consists of different kinds of tissues and cells. Different types of tumors can start in these different cell and tissue types. These different types of tumors have varying outlooks for survival and may be treated differently.

Neurons: These are the most important cells within the brain. They send signals through the axons. Axons may be very short (in the brain) or 2 to 3 feet long (in the spinal cord). Electric signals carried by neurons determine thought, memory, emotion, speech, muscle movement, and just about everything else that the brain and spinal cord do. Unlike many other types of cells that can grow and divide to repair damage from injury or disease, neurons quit dividing about 1 year after birth (with a few exceptions). Neurons do not usually form tumors, but they are damaged by tumors that start nearby.

Glial cells: Most brain and spinal cord tumors develop from glial cells. There are 3 types of glial cells – astrocytes, oligodendrocytes, and ependymal cells. Tumors of glial cells are sometimes referred to as a group and called gliomas. A fourth cell type called microglia is part of the immune system and is not truly glial in origin. Normal glial cells grow and divide very slowly. Glial cells are the supporting cells of the brain and continue to increase in number until the child is 5 years of age. At this time, the brain reaches its maximum size and will be the same size throughout oneÂ’s lifetime.

* Astrocytes help support and nourish neurons. When the brain is injured, astrocytes form scar tissue that helps repair the damage.

* Oligodendrocytes make myelin, a substance that surrounds and insulates axons of the brain and spinal cord. This allows oligodendrocytes to help neurons transmit electric signals through axons.

* Ependymal cells line the ventricles within the central part of the brain and form part of the pathway through which cerebrospinal fluid travels.

* Microglia represent 10% to 20% of the total population of glial cells in the brain. They are the immune (infection fighting) cells of the central nervous system.

Neuroectodermal cells: These are primitive cells that are probably the remains of embryonic cells and are found throughout the brain. The most common tumor that comes from these cells is the medulloblastoma, which arises in the cerebellum.

Meninges: These are specialized tissues that line the cerebrospinal fluid-filled spaces surrounding the brain and spinal cord. The meninges help form the spaces through which cerebrospinal fluid travels.

Choroid plexus: The choroids plexus is the area of the brain within the ventricles that makes cerebrospinal fluid, which nourishes and protects the brain.

Pituitary gland and hypothalamus: The pituitary is a gland found at the base of the brain. The hypothalamus is a part of the brain next to the pituitary gland. Both of these tissues help regulate the activity of several other glands. For example, they control the production of thyroid hormone by the thyroid gland, the production and release of milk by the breasts, and the production of male or female hormones by the testicles or ovaries. They also produce growth hormone, which stimulates body growth, and vasopressin, which regulates water balance by the kidneys.

The growth of tumors in or near the pituitary or hypothalamus, as well as surgery and/or radiation therapy in this area, can interfere with these functions. Consequently, a child may have low levels of one or more hormones and may need hormone treatments to correct any hormone deficiency.

Pineal gland: The pineal gland is not strictly part of the brain. It is, in fact, an endocrine gland that sits between the cerebral hemispheres. Its function is probably to make melatonin, a hormone that responds to changes in light.

Blood-brain barrier: Unlike most other organs, there is a barrier between the blood and the tissues of the central nervous system (brain and spinal cord) that keeps many drugs from getting into the brain, including most chemotherapy drugs that are used to kill cancer cells. However, some chemotherapy drugs can cross the blood-brain barrier to treat some malignant brain tumors.

Types of Brain and Spinal Cord Tumors

Sometimes brain tumors are found not to have started in the brain but rather to have spread, or metastasized, from some other part of the body. Tumors that start in other organs and then spread to the brain are called metastatic brain tumors and those that start in the brain are called primary brain tumors. This is important because metastatic and primary brain tumors are usually treated differently.

In children, metastatic tumors to the brain are much less common than primary brain tumors. Unlike other cancerous tumors, tumors arising within the brain or spinal cord rarely metastasize to distant organs. They cause damage because they spread locally and destroy normal tissue where they arise. This document only covers primary brain tumors.

Gliomas: This is not a specific type of cancer. Glioma is a general category that includes glioblastoma multiforme, primitive neuroectodermal tumors, anaplastic astrocytoma, astrocytomas, oligodendrogliomas, ependymomas, brain stem gliomas and optic gliomas. Because this word is often used in discussing brain tumors, it is defined here in an attempt to reduce confusion with it.

Tumors can form in any type of tissue or cell within the brain or spinal cord. Some tumors contain a mixture of cell types. The most common brain and spinal cord tumors of children are astrocytomas. The second most common are primitive neuroectodermal tumors (23%), and the third most common are other kinds of gliomas such as brain stem gliomas (15%). Ependymomas are the fourth most common at 9%. All the others are fairly uncommon and account for only 3%.

Astrocytoma: Most tumors that arise within the brain itself start in brain cells called astrocytes, a kind of glial cell. These tumors are called astrocytomas. About half of all childhood brain tumors are astrocytomas. Many astrocytomas cannot be cured because they spread widely throughout, and intermingle with, the normal brain tissue. They are called infiltrating astrocytomas. Sometimes infiltrating astrocytomas spread along the cerebrospinal fluid pathways. But it is very rare for them to spread outside of the brain or spinal cord.

Infiltrating astrocytomas are classified as low grade, intermediate grade, or high grade. A pathologist (a doctor specializing in the diagnosis of diseases by laboratory tests) will grade them based on how the cells from a biopsy specimen (sample of the tumor) look under the microscope. Low-grade astrocytomas are the slowest growing and the most common type of astrocytoma in children. Intermediate-grade astrocytomas, or anaplastic astrocytomas, grow at a moderate rate. The highest-grade astrocytomas, glioblastomas, are the fastest growing.

There are some special types of astrocytomas that tend to have a particularly good prognosis. These are juvenile pilocytic astrocytomas and subependymal giant cell astrocytomas.

* Juvenile pilocytic astrocytomas most commonly occur in the cerebellum but also occur in the optic nerve, hypothalamus, brain, or other areas.

* Subependymal giant cell astrocytomas occur in the ventricles and are almost always associated with tuberous sclerosis (an inherited condition which may also cause epilepsy, mental retardation, and tumors of the skin and kidneys).

Certain tumors possibly of mixed glial and neuronal origin that occur in children and young adults and rarely in older adults also have a good prognosis. One such tumor is the pleomorphic xanthoastrocytoma and another is the dysembryoplastic neuroepithelial tumor. Although they appear malignant under the microscope, these tumors are relatively benign and most are cured by surgery alone.

Oligodendrogliomas: These tumors start in brain glial cells called oligodendrocytes. They spread or infiltrate in a manner similar to astrocytomas and, in most cases, cannot be completely removed by surgery. A small number of oligodendrogliomas, however, are associated with long-term survival of 30 or 40 years. Oligodendrogliomas may spread along the cerebrospinal fluid pathways but rarely spread outside the brain or spinal cord.

Optic Glioma: Optic gliomas are low-grade tumors of childhood and are frequently associated with an inherited condition called neurofibromatosis-type 1. These tumors, which arise from the optic nerve, can sometimes be treated successfully by surgery. At other times radiation therapy or chemotherapy may be required. The tumors are rarely lethal but may cause substantial visual loss.

Ganglioglioma: This tumor contains both mature neurons and glial cells. It has a high rate of cure by surgery alone or surgery combined with radiation therapy.

Primitive neuroectodermal tumors: Almost one fourth of brain tumors in children are of this type. They are rare in adults. When these arise in the cerebellum, they are called medulloblastomas. They are fast-growing tumors that can spread along the spinal cord and meninges but can be treated. Up to 50% of cases are cured by surgery and radiation therapy, sometimes with added chemotherapy. About 15% of childhood brain tumors are medulloblastomas.

Primitive neuroectodermal tumors are called pineoblastomas when they occur in the pineal gland. Other forms of primitive neuroectodermal tumors are all rapidly growing tumors that frequently spread throughout the cerebrospinal fluid pathways. The outlook for pineoblastomas is not as favorable as for medulloblastomas.

Ependymomas: Almost 10% of brain tumors in children are ependymomas. These tumors arise from the ependymal cells that line the ventricles or central canal of the spinal cord. Ependymomas may block the exit of cerebrospinal fluid from the ventricles causing the ventricle to become very large – a condition called hydrocephalus. Unlike astrocytomas and oligodendrogliomas, ependymomas usually do not spread or infiltrate into normal brain tissue. As a result, some but not all ependymomas can be removed and cured by surgery. Spinal cord ependymomas have the greatest chance of surgical cure. Ependymomas may spread along the cerebrospinal fluid pathways but do not spread outside the brain or spinal cord. Ependymomas represent about 9% of childhood brain tumors.

Choroid plexus tumors: These tumors arise in the choroid plexus within the ventricles of the brain. They are usually benign and cured by surgery (choroid plexus papillomas). However, they may also be malignant (choroid plexus carcinomas).

Craniopharyngioma: This type of tumor arises above the pituitary gland but below the brain itself. Most craniopharyngiomas are very close to the optic nerve, making surgical removal difficult, because of possible damage to the childÂ’s vision. They may also compress the pituitary gland and the hypothalamus causing hormonal problems. Some are cured by surgery; others require radiation therapy.

Schwannoma (neurilemoma): This type of tumor starts in Schwann cells that surround and insulate cranial nerves and other nerves. Schwannomas are usually benign tumors that often form near the cerebellum and in the cranial nerve, which is responsible for hearing and balance. They also arise from spinal nerves after they have left the spinal cord and can compress the spinal cord causing weakness, sensory loss, and bowel and bladder problems. These tumors are rare in children and when present in this age group, particularly if there is more than one, might suggest an inherited familial tumor syndrome such as neurofibromatosis.

Meningioma: This type of tumor arises from the meninges, the tissue that surrounds the outer part of the brain and spinal cord. Meningiomas cause symptoms by pressing on the brain or spinal cord. Meningiomas are much less common in children than in adults.

Meningiomas are benign and are usually cured by surgery. Some meningiomas, however, are located dangerously close to vital structures within the brain and cannot be cured by surgery. Meningiosarcomas are rare but very malignant (cancerous) tumors that may come back many times after surgery or, in rare occasions, spread to other parts of the body.

Chordoma: This tumor starts in the bone at the back of the skull or at the lower end of the spinal column. Chordomas may come back many times over a period of 10 to 20 years causing progressive neurologic damage and deterioration. But they usually do not spread or metastasize to other organs.

Germ cell tumors: Germ cell tumors develop from germ cells that normally form eggs in women and sperm in men. During normal embryonic and fetal development, germ cells migrate to the ovaries or testicles and develop into eggs or sperm cells. Sometimes, however, a few germ cells may not migrate properly and end up in abnormal locations such as the brain. They may then develop into germ cell tumors similar to those that can form in the ovaries or testicles.

Germ cell tumors of the nervous system usually occur in children, most often in the pineal gland or above the pituitary gland. The most common germ cell tumor of the nervous system is the germinoma, which can be cured by radiation therapy and possibly chemotherapy in almost all cases. Other tumors of germ cell origin such as choriocarcinoma or yolk sac tumors are rarely cured by surgery. Both radiation therapy and chemotherapy are used in their treatment and in some cases this may not control the tumor completely. Germ cell tumors can sometimes be diagnosed without a biopsy by measuring certain chemicals in the cerebrospinal fluid or blood.

Neuroblastoma: Another kind of nerve cell tumor, which is not a brain tumor, is called neuroblastoma. This is the third most common cancer in children. Neuroblastomas rarely develop in the brain or spinal cord; most develop from nerve cells inside the abdomen or chest. This type of cancer is most commonly diagnosed during early infancy. Neuroblastoma is discussed in a separate American Cancer Society document.

Brain Tumors that are not Gliomas

* Chordoma
* Craniopharyngioma
* Medulloblastoma
* Meningioma
* Pineal Tumors
* Pituitary Adenoma
* Primitive Neuroectodermal Tumors
* Schwannoma
* Vascular Tumors

Chordoma

Chordomas, which are more common in people in their 20s and 30s than in other age groups, develop from remnants of the flexible spine-like structure that forms and dissolves early in fetal development and is later replaced by the spinal cord. Although these tumors are often slow-growing, they can metastasize or recur after treatment. They are usually treated with a combination of surgery and radiation therapy.

Craniopharyngioma

Craniopharyngiomas occur in the region of the optic nerves and the hypothalamus, a structure near the pituitary gland. Like chordomas, they develop from cells left over from early fetal development. They produce problems with vision and hormonal problems, slowing the child's growth and causing poor regulation of water balance. The benign craniopharyngioma is a tumor that usually affects infants and children, although it sometimes occurs in adults. While only a decade ago it was considered inoperable and rarely curable by surgery, it can now be removed with minimal or no brain damage in many cases because of the precision afforded by the surgical microscope and microsurgical techniques. Occasionally, if this tumor continues to grow and cannot be removed surgically, radiation therapy is also necessary.

Medulloblastoma

Medulloblastomas are the most common primitive neuroectodermal tumor (PNET), representing more than 25% of all childhood brain tumors. They occur in children more often than in adults. Medulloblastoma most often arises in the cerebellum, located in the lower back part of the brain and causes symptoms that include headache, nausea, vomiting and problems with muscle coordination (ataxia). Unlike other primary brain tumors, medulloblastoma has a tendency to spread throughout the nervous system if it remains untreated. In unusual cases, medulloblastomas may spread outside the nervous system, to the lymph nodes, bone marrow, lungs or other parts of the body. In many cases, they are treated with surgery and radiation therapy alone. They are fast-growing tumors, but because they are very sensitive to radiation therapy and chemotherapy they can often be treated effectively.

Meningioma

A meningioma is a common brain tumor that originates from the meninges, the thin membranes or lining that cover the brain and spinal cord. As they grow, meningiomas compress adjacent brain tissue. Meningioma symptoms are often related to this compression of brain tissue, which can also affect cranial nerves and blood vessels. In some cases, meningioma growth can also extend into the bones of the head and face, which may produce visible changes. Meningiomas account for about 27% of all primary brain tumors and tend to affect more women than men. Most meningiomas are considered benign tumors. However, unlike benign tumors elsewhere in the body, benign brain tumors can
sometimes cause disability and may sometimes be life threatening. In many cases meningiomas appear to grow slowly. Other meningiomas grow more rapidly or have sudden growth spurts. There is no way to predict the rate of growth of a meningioma or to know for certain how long a specific tumor was growing before diagnosis. Although most people develop a single meningioma, it is
also possible to have several tumors growing simultaneously in different parts of the brain and spinal cord. Because recurrent tumors cannot be predicted, it is very important for meningioma survivors to receive regular follow up scans as part of their lifetime health care in order to avoid critical care being neglected.


Pineal Tumors

These tumors arise in the region of the pineal gland, a small structure deep within the brain. They account for about 1% of brain tumors, but make up 3% to 8% of the intracranial tumors that occur in children. At least 17 different types of tumors may occur in this area, many of which are benign. The three most common types of pineal region tumors are gliomas, germ cell tumors and pineal cell tumors. Surgery is absolutely necessary to obtain a sample of tumor tissue so the pathologist can confirm a precise histological diagnosis, which is essential in planning the appropriate therapy. Benign pineal tumors can be removed surgically. The germinoma, the most common malignant tumor in this area, can be cured in more than 90% of patients. Other malignant germ cell tumors occurring in this region are treated with chemotherapy followed by radiation therapy. Over the past 5 years, the prognosis for children with pineal tumors has improved dramatically.

Pituitary Adenoma

The pituitary gland is a small oval structure located at the base of the brain in the center of the head, behind the eyes and optic nerve. It is about the size of a pea but is very important because it secretes several chemical messengers known as hormones, which help control the body's other glands and regulate growth, metabolism, maturation and other essential body processes. A tiny tumor located just next to the gland, pituitary adenomas account for about 10% of brain tumors. Doctors classify pituitary tumors into two groups - secreting and nonsecreting. Secreting tumors release unusually high levels of pituitary hormones, triggering a constellation of symptoms. They are usually much smaller than the gland when they begin to cause symptoms and the symptoms depend on the tumor's size and the kind of hormone the tumor secretes. Prolactin-secreting adenomas affect sexual characteristics and cause impotence in men. Adenomas secreting growth hormone cause acromegaly (abnormal body growth, enlarged facial features, hands and feet) and gigantism (excessive size and stature). The less common adrenocorticotropic hormone-secreting adenoma causes Cushing's disease. Some adenomas secrete a combination of these or other hormones and some secrete none. Almost all adenomas are benign, but their slow expansion compresses normal structures that surround it, suppressing normal pituitary function and sometimes causing headaches or problems with vision. Pituitary adenomas rarely metastasize or spread to other areas of the body. They are removed in an operation using microsurgical techniques, a very successful form of treatment for the majority of patients.

Primitive Neuroectodermal Tumors

Primitive Neuroectodermal Tumors (PNETs) usually affect children and young adults. Their name reflects the belief, held by many scientists, that these tumors spring from primitive cells left over from early development of the nervous system. PNETs are usually very malignant, growing rapidly and spreading easily within the brain and spinal cord. In rare cases, they cause cancer outside the central nervous system. Medulloblastomas are the most common PNET. Other more rare PNETs include neuroblastomas, pineoblastomas, medulloepitheliomas, ependymoblastomas and polar spongioblastomas. Because their malignant cells often spread in a scattered, patchy pattern, PNETs are difficult to remove totally through surgery. Doctors usually remove as much tumor as possible with surgery then prescribe high doses of radiation and, in some cases, chemotherapy.

Schwannoma

Schwannomas arise from the cells that form a protective sheath around the body's nerve fibers. They are usually benign and are surgically removed when possible. One of the more common forms of schwannoma affects the eighth cranial nerve, which contains nerve cells important for balance and hearing. Also known as vestibular schwannomas or acoustic neuromas, these tumors may grow on one or both sides of the brain.

Vascular Tumors

These rare, noncancerous tumors arise from the blood vessels of the brain and spinal cord. The most common vascular tumor is the hemangioblastoma, which is linked in a small number of people to a genetic disorder called Von Hippel-Lindau disease. Hemangioblastomas do not usually spread and doctors typically treat them with surgery.

(This information was taken respectively from here)

Shunt for Hydrocephalus (Water in the Brain)

Taken from here

The most common surgery for the treatment of hydrocephalus (water on the brain), is the insertion of a shunt - a device that diverts fluid from the brain into the abdominal cavity where it is safely absorbed into the blood stream. Though a shunt may be inserted in infants, children and adults, the procedure is essentially the same regardless of the size of the patient.

Anatomy and Physiology

• In a normal brain there are four fluid filled spaces called ventricles (Figure 1)
  
  1. There are two large ventricles (lateral ventricles) located on either side of the brain
     
  2. Two other ventricles (the third and fourth ventricles) are placed along the midline
     
• Within the ventricles are tufts of vascular tissue called the choroid plexus. As blood flows through the choroid plexus it distills a clear watery fluid into the ventricles called cerebrospinal fluid, or CSF
  
• CSF flows from the ventricles towards the surface of the brain and returns to the blood (Figure 2)
  
  1. From the lateral ventricles the CSF flows into the centrally placed third ventricle and then through a narrow channel called the aqueduct, into the fourth ventricle
     
  2. CSF then flows over the surface of the brain in the subarachnoid space, an area between the brain and the membrane (dura) lining the inside of the skull
     
  3. The CSF then returns to the blood by passing into the large veins that drain the brain called sinuses
  

Figure 1 - Anatomy of the ventricles.

Figure 2 - CSF flows from the lateral ventricles into the third ventricle, through the aqueduct of Sylvius, to the fourth ventricle and finally over the surface of the brain to the dural sinuses where it is absorbed into the blood.

Picture taken from www.Yoursurgery.com

Craniotomy

A craniotomy is the surgical removal of a section of bone (bone flap) from the skull for the purpose of operating on the underlying tissues, usually the brain. The bone flap is replaced at the end of the procedure. If the bone flap is not replaced, the procedure is called a craniectomy. A craniotomy is used for many different procedures within the head, for trauma, tumor, infection, aneurysm, etc.

Anatomy

• At birth the bones that make up the cranium or skull are separated, allowing the head to pass through the birth canal. (Figure 1)
  
• As the individual matures, the bones fuse together so that by late teens the bones form a solid union
  
• The various bones of the skull are the frontal, parietal, temporal, occipital, and sphenoid, (Figure 2)
  
• The scalp covers the skull
  
• Within the skull lie:
  
  1. The brain, which is divided into four major parts- the right and left cerebral hemispheres, the cerebellum and the brainstem (Figure 3).
     
• The cerebral hemispheres form the largest portion of the brain and can be regarded as the 'thinking' part of the brain and are involved in movement, sensations, speech and creation of ideas
  
• Each cerebral hemisphere is divided into four lobes - frontal, parietal, temporal and occipital
  
• The surface of the hemispheres is folded upon itself and presents as various grooves (sulci) and bulges (gyri). The two cerebral hemispheres are connected across the midline by a large band of brain fibers called the corpus callosum that transmit nerve impulses between the hemispheres
  
• The cerebellum lies at the back of the brain under the occipital bone and is involved in fine tuning movement
  
• The brainstem lies in front of the cerebellum and is attached above to the cerebral hemispheres, behind to the cerebellum and below to the spinal cord
  
2. The meninges (the membranes that line the inside of the skull (dura) and cover the brain (pia-arachnoid). A large fold of dura called the falx lies above the corpus callosum and separates the cerebral hemispheres. (Figure 4) Another large fold of dura, the tentorium, separates the cerebral hemispheres from the cerebellum. The brainstem passes through a hole in the front of the tentorium. The space that lies beneath the tentorium, which contains the cerebellum and brainstem, is called the posterior fossa
   
3. The blood vessels that feed the brain
   
4. The cerebrospinal fluid (the fluid that bathes the brain) originates within the ventricles (spaces) within the brain

Pituitiary Tumor

by John R. Mangiardi, M.D. and Howard Kane, Wm.

The pituitary gland is a half-breed in many ways. It is not really a part of the brain, but rather hangs beneath it. Half of the gland comes down from the brain (the posterior lobe which controls the body's water levels and secretes the hormone ADH -- anti-diuretic hormone). The other half comes from tissues originating from the roof of the embryonic mouth, the anterior lobe which controls sex hormone levels, lactation, growth hormone, body steroids, and the thyroid gland).

The pituitary is responsible for almost all of the body's hormonal systems, taking all of its cues from the hypothalmus, the hidden and very deeply located Grand Wizard of the brain. The hypothalmus also controls such activities as body temperature, sexual drive, appetite, blood glucose levels, and sleep/arousal behavior patterns.

As elsewhere in the brain, tumors of the pituitary gland behave according to their cell of origin. Most of these tumor are truly benign, although on occasion they may prove to be malignant (pituitary carcinomas). The list of cells of the pituitary determines the tumor types, as well as the clinical syndromes related to each. Almost all have the good prognosis which calls for total removal. On the other hand, almost all can eventually become "malignant by position."

This is especially true when the tumors grow off to either side, involving the jam packed structures behind both eyeballs, called the "cavernous sinuses." The pituitary gland is located exactly between these two structures, which contain the nerves that control eye movement and the major arteries that feed the brain (carotid arteries, the veins that drain the eyes and other nerve related structures). Therefore, these tumors may occasionally present the patient with double vision, or even something called "Pituitary Apoplexy" (severe sudden headache, loss of and/or double vision, protruding eyeball).

Each tumor, because of its extraordinarily high hormonal output, creates a characteristic clinical syndrome that brings attention to the tumor. Because the pituitary gland is located directly beneath the place where the nerves cross, coming from the eyes to the brain (the optic chiasm), many tumors also present -- along with the hormonal problems listed below -- loss of peripheral vision.

Hormonal Problems

Gigantism: This syndrome is caused by pituitary tumors on the growth hormone secreting cells of the pituitary gland. Remember Lurch from the James Bond movie -- large hands, protruding jaw, severe arthritis, huge size, protruding eyebrows, plus other systemic problems -- a classic example of gigantism.

Cushings Disease: This syndrome is caused by tumors on the ACTH (Adrenal Corticotrophin Hormone) secreting cells of the pituitary gland. Patients with this problem develop fat deposits in strange places (Moon face, Buffalo hump on the back of the neck), spontaneous scarring of the skin along the belly that look striated, pimples in adults, high blood pressure and elevated body temperature. These tumors are usually so small that the surgeon might have a difficult time finding the little "bad pearl" in the gland during surgery. This is the one time when small can be bad, especially if the surgeon is unable to locate and remove the tumor! ACTH secreting tumors, although small and troublesome, are readily cured by surgery alone.

Prolactin Syndrome: This syndrome is caused by tumors on the prolactin secreting cells of the pituitary gland. The tumors are the most common of all the pituitary tumors. Production of breast milk in women who are not pregnant, loss of menstrual cycle, and loss of bone calcium are all hallmarks of this tumor. When small, it may be cured; when large, it may cause visual problems and require other (e.g. radiation) therapy. Many women with this tumor visit their gynecologist thinking that they might be pregnant.

Growth hormone secreting tumors may very occasionally be treated with drugs, but most often must be removed surgically.

Non-Secreting Tumors: Can be treated by surgery and/or radiation. These patients almost always have problems with vision, as the hormonally quiet tumor grows to oversized proportions, actually growing to the point of lifting up and stretching the optic nerves (especially where the nerves from both eyes cross as they travel to the brain). The treatment of these tumors is variable. Prolactinomas are most often treated non-surgically with drugs that inhibit prolactin production (parlodil). Microprolactinomas sometimes never really grow over long periods of time, and do not require surgery.

All pituitary tumors can be treated by radiation, especially with the improvements brought on by focused beam radiation (liner accelerator and proton beam). The idea of radiosurgery originated in this venue. One serious problem with radiation has been loss of function in the remainder of the pituitary gland, requiring patients to depend on hormone supplements for the continuation of their lives. Another has been the inability to quickly reverse visual loss in large tumors using radiation. On the other hand, radiation has been used as a very successful adjunct in larger tumors that pose a threat to long term survival.

Surgery on Pituitary Tumors

The wonderful surgical achievement of the modern age is the combination of improved lighting, the surgical microscope, and computer assisted navigational instrumentation now used in the O.R. The pituitary gland lies just above the air spaces in the nose (if you'd stick a pencil through your nose hard enough, you'd end up in your pituitary gland). In fact, the word "pituita" (like the word "ptuey!") refers to the not so delicate production of "snot." In medieval times in Europe, and in China today, it is thought that "pituita" was something good to get rid of, serving as a relief valve for bad humors of the brain. In other words, spitting was good for the soul as well as one's health.

Thus, by traversing the structures just beneath the skull through the nasal cavities, brain surgery can be avoided and the risk of approaching the pituitary gland can be enormously reduced.

Decision Making for Pituitary Tumor Surgery

It's an Emergency: Patients who have a large pituitary tumor (and often don't even know about it) will occasionally develop a kind of pituitary "stroke," called pituitary apoplexy. This occurs after the tumor outgrows its blood supply and suddenly enlarges (due to swelling) after it infarcts (a type of local stroke), or begins bleeding within the tumor. The enlargement causes severe headache and/or double vision, because the nerves that control the eye located next to the gland are pressed upon. It can also cause loss of vision (because the gland swells upward, pressing from beneath the optic nerves above). Surgical decompression is an emergency procedure because permanent blindness may result if left untreated.

Surgery Is the Best Way to Go

Cushing's Disease: Because the tumor is so small, a cure is possible when removed. Thus, surgery is the best way to go. Moreover, the remainder of the gland is left intact, and will function normally thereafter.

Large tumors with liquified (necrotic) centers: In these cases, the surgery is easy, and the improvement is immediate. Any remaining tumor beyond the confines of the surgical field can be safely treated by other standard therapies (e.g. radiation therapy).

Medium sized tumors: Still within the confines of the pituitary gland. As with the Cushing's tumors, the tumor can be completely removed and the gland saved for normal function.

A 'Hold' on the Surgery

Prolactinomas: Should always be treated initially with medication (anti-DOPA agents such as Parlodil, Bromocriptin, etc.). Even large tumors that most need to be treated by either surgey or radiosurgery should be pretreated with these drugs to shrink the tumor away from vital brain structures before surgery should be contemplated.

Microprolactinomas: Surgically, nothing need be done for as long as possible. Some of these tumors appear to just sit there for years, even decades.

Extremely large tumors that cause little visual or other brain problems: In treating these tumors, particularly in older people, the physician should consider radiation therapy to stop the progression of these tumors. A surgical cure is usually not an option, for the substantial surgical risk entailed.

Pineal Region Tumor

As mentioned in the PRIMER, the pineal gland hangs on the brain behind its very center. French 18th century scientist Rene Descartes thought that the pineal gland was the core of the soul, noting that it was the only unpaired organ in the body, and located in the center of the brain. He thought that the gland controlled the movement of the various body "humors." In fact, the pineal gland is the "third eye" of the brain, and is responsible for telling the brain when it is day or night. It also controls the body's hormonal systems, sleep-wake cycle, and other so-called "circadian" body rhythms. It is in essence, the body's internal clock."

The gland produces a hormone called melatonin, (now a popular over-the-counter seller). Melatonin levels are what directly influence the function of various brain centers (appetite, sleep, the hypothalamus and pituitary gland). The cells of the pineal gland are unique in that they are not related to either the support cells of the brain (i.e. astrocytes, etc.), nor to the brain neurons. Rather, they develop on their own. For this reason, true pineal cell tumors are quite different from other brain tumors.

The pineal gland is also filled with brain support cells (astrocytes) and has a very dense input of nerve fibres coming from the eyes via a very circuitous and complicated route. Thus, the tumors of the astrocyte support cells of the pineal region are the same as the astrocytomas and GBM.

Pineal tumors, themselves, vary. They include:

• Pinealocytoma ("benign" pineal cell tumor)
• Pineoblastoma (more aggressive pineal cell tumor)
• Pineal germinoma ( aggressive primitive cell tumor growing in the pineal region)
• Pineal teratomas (rare tumors of multiple cell types that grow in the pineal region)
• Pineal Cysts (most often not treated, unless large enough to cause hydrocephalus or visual symptoms)

Making the Diagnosis

A combination of CAT scan, MRI, and spinal fluid studies (including "markers" such as AFP, and spinal fluid cytology), will aid the surgeon to deliver a very good guess or outright diagnosis.

Treatment Decisions -- Tumor Biopsy

With all of these possibilities in such a small area, it is no wonder that most physicians feel strongly that at least a biopsy should be taken prior to considering a treatment course.

1. Surgical Removal. These tumors should be approached surgically at first, with a best effort approach to remove as much as, if not all, of the tumor. With current surgical technology, the down side has essentially been reduced to well below the 2% risk mark, making the decision to operate much less difficult than previously. Today, the surgery can be minimized so that recovery time is shortened. Some patients with larger tumors may also develop hydrocephalus, requiring the placement of a shunt at the time of surgery or thereafter.
2. Radiation. Some centers perform radiation, at least in a "test" dose (in the case of the germinoma) since some of the primitive tumors are quite sensitive, a full course of radiation might be considered.
3. Craniospinal axis. If the spinal fluid cytology is positive, so-called "craniospinal" axis therapy may be considered. This is done because some of these tumors will "seed" down from the brain into the spinal canal.
4. Chemotherapy. Many chemotherapy choices may be available. Some of these tumors are quite sensitive to chemotherapy, accounting for the vigorous chemo-approach of many neurooncologists to such lesions.

Meningioma

by John R. Mangiardi, M.D. and Howard Kane, Wm.

The meningioma is the neurosurgeon's "friend" and often his most enduring challenge. For both the physician and patient, this tumor carries a true tag of benign. It also carries the possibility of "cure" in approximately 80% of cases. Thus, the long-term outcome for a patient with this tumor is a direct function of the skill and assiduousness of the surgeon who removes it.

Elsewhere in the Brain Surgery Information Center's Primer on Brain Tumor Biology, it was mentioned that "benign" often does not really mean benign. Be assured that in this case, the tumor really is benign.

As mentioned earlier in the Primer, each type of brain tumor arises from a specific cell type. The cell of origin for the meningioma is call the arachnoid cap cell, found on the surface coverings (called meninges) of the brain in the paccionian granulations. These serve as the one-way valve system between the water system of the brain and the veins that drain from the brain to the heart.

Interestingly, these tumors have an embryologic relationship with cells found in the muscle layer of the utereus. In fact, it is exceedingly difficult for the pathologist to distinguish the meningioma from the fibroid tumors of the utereus under the microscope. Also, they share the characteristic female hormonal receptors (estrogen and progesterone) on their cell surfaces. This characteristic has lead to the testing of anti-estrogen receptor agents, such as tamoxifin, as a growth-inhibiting agent in these tumors. Clinical studies to date have failed to provide siginificantly positive results.

Meningiomas are rarely malignant in their behavior. But when malignant, meningiomas grow rapidly and are destructive; they are quite difficult to treat, and recur oftentimes in less than a year after surgical removal. They are also difficult for the pathologist to diagnose under the microscope. Probably the only finding that correlates well with the diagnosis is that of numerous cells seen in division ("mitosis"). The pathologist may occasionally speak of brain and skull invasion, cells with an abnormal appearance, or other bizarre findings, however none of these completey fit the diagnosis. Ultimately, the diagnosis is determined by the activity of the particular tumor over time.

A cousin to the meningioma is the hemangiopericytoma. The cell of origin for this tumor is the perivascular pericyte (located around blood vessels). Although very similar to the benign meninigiomas, these tumors tend to recur with great rapidity (less than one year) and frequency. Some physicians classify these tumors with the malignant meningiomas.

Acoustic Neuromas

One scenario might be: you can't hear anything when you put the telephone to one of your ears. Your doctor now delivers the bad news -- that you have a brain tumor, AND the Good News -- that it is perfectly benign. You are bombarded by different therapy options (Gamma Knife, Surgery, etc.) including the idea to forget about the whole thing. Everyone and their brother and/or sister has a strong opinion; only you are left to make the decision.

Welcome to the world of acoustic neuromas!

This tumor (called a "schwannoma") arises from the myelin forming cells (Schwann cells") of the 8th cranial nerve at the point where the peripheral part of the nerve meets the brain part of the nerve (called "Hensen's node"). Hensen's node is usually located in the inner ear canal that leads to our hearing apparatus, called the "acoustic meatus." This nerve is actually three nerves in one, two "vestibular" nerves (upon which the tumor actually grows) and the hearing nerve. Immediately associated with these nerves is the 7th cranial nerve, the nerve that controls the muscles of the face, salivation, tearing, and taste. The tumor grows just next to the brain stem, and when enlarged may actually compress it. Larger tumors also may involve the swallowing nerves down below, as well as the 5th nerve above which controls sensation to the face and eye.

In other words, this is a very tightly packed and difficult area for involvement. Patients may present any combination of symptoms related to malfunction of these nerves, depending on the size, the pressure and location of the tumor.

In patients with an inherited disease called "Neurofibromatosis," a slightly different type of tumor grows, the "neurofibroma." This tumor tends to involve the whole nerve rather than displace a nerve as does the "schwannoma." In general, the neurofibroma is somewhat more difficult to handle.

Tumor Classification

Size determines therapeutic outcome. Therefore, a grading system has been devised to allow both physicians and patients to tailor their expectations for outcome accordingly.

• Grade I - Tumor is small, occurring only within the internal auditory canal itself.
• Grade II - Tumor extends into the fluid spaces around the brainstem
• Grade III - Larger tumor (usually up to 2.5 cm in diameter). Extends up to the brainstem.
• Grade IV - Very large tumor (up to 5 cm in diameter). Compresses the brainstem, often involves the nerves of swallowing and the 5th cranial nerve (face and eye sensation)

Surgical Decisions

Ways to remove the tumor

1. Translabrynthine approach. This approach is ideally suited for smaller tumors, especially when all or most of functional hearing is lost in that ear. This approach always sacrifices hearing, so it is not used if there is a chance to save the hearing.
2. Retromastoid approach. This approach is used for small tumors when hearing preservation is a possibility. Saving hearing in these cases is about 50:50. It is also chosen for larger tumors, or for schwannomas that potentially grow from other cranial nerves (e.g. 7th, 5th, 9th ).
3. Middle fossa approach. A favored approach used by only a few surgeons. Hearing can also be preserved in this way.

Surgical Risks

Cerebrospinal fluid leakage. Surgery in this area may lead to spinal fluid leakage in up to 20% of cases. This is most often temporary; other procedures may be required to treat this problem if it persists. The obvious risk of CSF leakage in meningitis requires antibiotic treatment as well. With the today's microsurgical techniques (very small incisions, usage of fibrin glue and new closure techniques) the risk of CSF leakage has been greatly reduced.

7th Nerve Loss. This is a most distressing problem, especially for younger patients. The eye does not close well, tearing is difficult to control, the face droops and friends look at you strangely. Sensation to the eye might be lost as well, causing abrasions to the cornea. In cases of large tumors with a thinned out nerve that is splayed over the surface of the tumor, the nerve is physically saved during surgery, but it may not function well or only partially recover.

5th Nerve Loss. Loss of sensation to the face and eye is not only disturbing, but it is also potentially dangerous. The cornea of the eye can be injured when sensation is lost, causing loss of vision.

Swallowing Nerve Loss (9th and 10th nerves). Loss of ability to swallow effectively may lead to aspiration pneumonia when secretions and food travel into the lungs rather than down the esophagus.

Solutions for cranial nerve loss (7th Nerve). It is now possible to effectively reestablish 7th nerve function using a number of methods. Most of these include reconnection of the nerve with either nerve grafts and/or other nerves (e.g. the opposite of the 7th nerve -- the 12th nerve). Other strategies include plastic surgery operations to suspend the face and opthamalogic placement of a gold weight in the eyelid. In cases of partial dysfunction to the nerve, electrical stimulation to the face may allow the facial muscles to stay in shape while the nerve repairs itself.

Swallowing Nerves. Problems with swallowing are almost always temporary. Serious loss of swallowing function can be partially repaired via a number of different surgical procedures. In serious cases, a temporary tracheostomy may be needed until swallowing function returns.

Radiation Therapy. Focused beam radiation (e.g. the Gamma knife) has been greatly advocated as a new technology for benign brain tumors, especially the acoustic neuroma. Although tantalizing, and early studies show that acoustic neuromas tend not to grow and may even shrink with this therapy, a few notes of caution are in order:

1. Historical studies have shown that radiation therapy to the brain and its coverings, even at low dosages, can cause serious problems after a number of years. One good example took place in Israel during the 1950's, when childern and young adults were treated for a scalp condition called tinea capitis with very low dose radiation therapy (only 1000 Rads!). Over the years (10-30) that followed, many of these people developed meningiomas of the brain. Some even developed malignant astrocytomas. We also know that patients who survive the usual dosage of radiation to the brain may develop radiation necrosis and in some cases malignant brain tumors in the area radiated.
2. Focused beam radiation usually has a dosage of 10,000 -12,000 Rads, enough to give one pause when thinking of long-term results.
3. Long term results (i.e. greater than 10 years) are still not in.
4. If a tumor were to continue to grow or recur, future surgery in the area of radiation would be difficult, because of local radiation changes (scarring) to the surround tissues and nerves.
5. Complete surgical removal has been proven to be curative.
6. The downside of surgery has been markedly reduced, with microsurgical approaches limiting the skull opening to the size of a quarter.

Brain Tumors

by John R. Mangiardi, M.D. and Howard Kane Wm.

Brain tumors -- the very words strike fear in the heart of anyone threatened by one. It once was considered one of the most frightful events that could occur. Today, however, with improving technology and the gradual unfolding of scientific understanding of the basic biology of brain tumors, patients and families can look to the future with considerably more hope.

Scientists, physicians and researchers ponder the limitless questions concerning brain tumors: What does a brain tumor eat for breakfast? How does it really function? Why can't we get rid of this thing now? Why did person A get a brain tumor and not B? What causes brain tumors? These are just a few of the hundreds of questions plaguing scientists, researchers, as well as patients, their families and their physicians.

Firstly, the brain is an incredibly complex organ. Like a true resident in an Ivory Tower, the brain lives apart from, and quite differently than, the rest of the body. The brain contains about 10 Billion (10,000,000,000) working brain cells. They are called neurons and make over 13 Trillion (13,000,000,000,000) connections with each other to form the most sophisticated organic computer on the planet -- maybe even the universe. By today's computer standards, the brain far exceeds any network of linked state-of-the-art computers.

Despite such complexity, most of the brain is made up of supporting cells. The vast majority of these are called astrocytes. These cells are the support "stuff" of the brain, and serve as a scaffold for the working brain cells and other structures. Oligodendrocytes, another type of brain cell, are much fewer in number; they are primarily responsible for making the covers (called myelin) for the vast wiring system of the brain. The ependymal cells are fewest in number; they simply cover the inner surfaces of the brain called ventricles.

The entire brain floats in a self contained sort of womb, and like a fetus, is surrounded by and filled with a watery fluid known as cerebrospinal fluid (CSF). These fluid spaces, when obstructed by a tumor, may enlarge and cause pressure within the closed box of the hard skull to increase dangerously. This is referred to as hydrocephalus or water-on-the-brain.

The brain has various coverings (meninges or dura), just like a wet football with its inner bladder and outer pigskin shell. They hold things securely in their proper place. The cells of the meninges are unique, and some of them are capable of filtering the brain fluid (CSF) back into the bloodstream by a sort of one way valve system. They are called arachnoid cap cells.

Also, attached to the brain are a couple of hangers on. Literally, hanging beneath the brain is the Pituitary Gland, a kind of Wizard of Oz box of hormonal cells that control almost all of the body's hormonal systems. Hanging just behind the brain is a little pine cone called the Pineal Gland, the "third eye." It tells the body when it is day and when it is night via its now popular brain hormone, melatonin.

Brain tumors originate from one cell at a time and travel to other brain cells, unlike other cancers (e.g. bladder and blood cancers). So, it makes sense that the tumors of the brain occur in a frequency that corresponds directly with how many of each cell type are present in the first point of tumor.

Brain tumors can arise either from the brain itself (primary brain tumors: astrocytoma, glioblastoma, oligodendroglioma, ependymoma), or its coverings (meningiomas, pituitary tumors, pineal tumors), or the nerves at the base of the brain (acoustic neuromas, schwannomas), or even from outside the brain (metastatic brain tumors) . This last case occurs when cancer cells travel through the bloodstream and lodge in the brain.

The vast majority of brain tumors are primary. Of these, the malignant astrocytoma and glioblastoma multiforme are the most common, and are responsible for the bad reputation that brain tumors carry.

Important Points Regarding Primary Brain Tumors

• * Brain tumors are different!
• * Brain tumors are not cancers.
• * They grow only in the brain itself, and almost never travel beyond the brain.
• * They don't metastasize. Treatment should be limited to the brain.
• * Benign is not always "benign." Low grade gliomas, although called benign, often grow inexorably, albeit slowly.
• * They involve the whole brain. Even though they seem to grow locally, tumor cells travel around the brain and are always found beyond the tumor margins, even on the opposite side of the brain.
• * Benign tumors may be malignant by location -- easy tumors in tough places.
• * True tumor margins do not exist. Total removal by local therapy (surgery, radiation, heat, cold, etc.) is not possible.
• * The brain is immunologically isolated.
• * The Blood:Brain barrier is real.
• * Many helpful treatments can't enter the brain via the bloodstream.
• * Primary brain tumors are polyclonal. They are actually many tumors in one (sometimes over a thousand!)
• * Each clone has differing sensitivity (or resistance) to anti-tumor treatments.
• * Each clone has its own cell cycle time, doubling time, etc.

With these observations in mind, the therapy of primary brain tumors has been sharply focused, because only the brain needs to be treated, not the entire body.

But, the treatment of brain tumors is extremely difficult because of polyclonicity, the Blood:Brain barrier, the diffuse infiltrative nature of these tumors, and the perilous location of some tumors.

CONCLUSION:

The only therapy(ies) that could possibly cure primary brain tumors must:

1. Treat the whole brain 2. Cross the Blood:Brain barrier 3. Get to each and every tumor cell 4. Kill all cell types within the tumor 5. Spare the remaining normal brain.

We take other factors into consideration as well. Using the Glioblastoma Multiforme (GBM) as an example, the physician needs to consider the following factors:

GROWTH DYNAMICS (GBM)

Growth Fraction = 20 % (Only a percentage of the tumor is growing at any one time)

Cell Cycle Time = 2 - 5 Days (This is how long it takes a growing cell to reproduce)

Cell Loss = 80 - 90 % (A high percentage of cells spontaneously die off)

Doubling Time = Around 7 Days

Therefore, any therapy aimed at controlling the growth of this tumor must recognize the above dynamics. Therapy must catch the cells at the appropriate phase of the cell cycle (when they are sensitive to treatment), take into account tumor doubling time, and acknowlege that the growth fraction is relatively small.

There are other problems to take into account as well:

Many cells live in a low oxygen environment (hypoxic). These hypoxic cells are:

• * radio-resistant
• * often chemotherapy resistant
• * far from the blood supply

The blood supply to the tumor is quite peripheral, surrounding rather than entering it. The center of the tumor (necrotic center) contains living tumor cells. Therefore, much of the tumor is virtually unavailable to chemotherapy, radiation therapy, immunotherapy or any other therapy.

Standard Therapy

To date, the best treatment for the malignant astrocytoma and GBM is a combination of:

• * Surgery (Gross total removal, i.e. 80 - 99 %)
• * Radiotherapy (5,000 - 6,000 Rads)
• * Chemotherapy (BCNU)

This combination is now "standard therapy", and has been the benchmark to which all other therapies have been compared. Unfortunately, this protocol represents only a single month of improvement over surgery alone! In other words, in over thirty years of clinical research, very little has been done with any outstanding success! (The newly formed Foundation for Neuosurgical Research, however, is dedicated to changing this track record. It will be focused specifically on brain tumor patient improvement alone!)

"Standard therapy" in this country has failed to alleviate, despite spawning 400-plus new, different protocols. This presents a mind-boggling problem for patients and their families, especially when ofttimes they don't even know what a brain tumor really is! Added to the confusion is the enormous proliferation of new technologies becoming available to treat these tumors: lasers, stereotactic computers, cryosurgery, thermal killing machines, ultrasound, radiosurgery, the Gamma Knife, the X-Knife, photoirradiation, blood:brain barrier disruption, boron neutron capture, etc.

Where do science and technology meet the logic of brain tumor biology? What is purely experimental? What is logically worth the effort? What are the numbers? Where does a therapist's enthusiasm for new technology or protocol end, and logical approach to these tumors begin? These are just some of the newer questions which arise during the first weeks after coming in contact with the problem of a malignant brain tumor.

A Guide to the Perplexed

Considering all of the above, the following is a suggested method for approaching the therapy of malignant primary brain tumors. Be logical.

Imagine that a particular tumor weighs about 100 grams. Consider the following:

100 gm of tumor = 100 billion cells, approximately.

If a tumor size can double in volume in a matter of weeks, it would make sense to decrease the size of the mass of the tumor right away. Otherwise, a patient could not make it through a treatment course. Surgery is the way to radically reduce the volume of a tumor, removing anywhere from 80 to 99% of the tumor mass. Recent advances in surgical technologies have aided in the removal of brain tumor tissue with a newer, higher net percentage tumor reduction of 90-99%. These include computer assisted stereotactic surgery, laser instrumentation (carbon dioxide, argon, and Yag), ultrasonic aspiration, operative phototherapy, etc.

Consider the following:

• 90% removal of tumor (100,000,000,000 cells), leaves 10 billion cells
• 99% removal of tumor (100,000,000,000 cells), leaves 1 billion cells


Thus, no matter how good the local surgical therapy is, the patient is still left with at least 1 billion tumor cells!

There now remains the combination of therapies: follow up the initial volume reduction therapy with something else. The usual choices are radiotherapy or chemotherapy. In the best of circumstances, one could expect another 90-99% reduction in tumor cell number. Another 90-99.9 % cell reduction still leaves 1 million to 100 million cells.

The logical procedure now would be to hit the tumor again with yet something else, (usually radiation or chemotherapy) that might attack the remaining cell population.

If left without treating a third time, it is possible that the tumor could return to its original size in as few as 6 weeks, factoring in the numbers mentioned above.

Local therapy vs. Whole brain therapy

A number of local therapies are under study at present, including focused beam radiotherapy proton beam radiation - the Gamma knife, linear accelerator - the "X-knife," brachytherapy - radiation seeds implanted into the tumor bed, cryotherapy, thermal therapy, ultrasonic therapy, phototherapy, drug and immunotherapies injected locally into the tumor bed via an Omaya reservoir, intrarterial therapy - selective exposure of involved brain via angiography. In other words, we can "zap" the tumor locally in various ways: freeze, heat, shake, pickle, radiate and expose it to other local insults.

Local therapy, however, still leaves a significant number of very malignant cells left in the brain far away from the area of a local treatments exposure. By design, then, all local therapies always leave that 1 million to 100 million cells behind to grow back in a matter of weeks or months, simply because they never address those tumor cells that lie beyond the area of treatment. Whole brain therapy, on the other hand, heeds the logic that these tumors must always be considered to involve the entire brain. Therefore, the only treatment that could logically provide any hope for cure, or at least long term remission, should treat the entire brain. Some such therapies include: systemic chemotherapy, whole brain radiation, and theoretically, immunotherapy.

Radiotherapy: The dosage needed to cure all malignant brain tumors is approximately 12,000 Rads. However, such a high dosage is also extremely neurotoxic and therefore deadly. This is why radiation doses of 5,000 to 6,000 rads has been agreed upon. These doses can have an "acceptable" brain toxicity rates. Unfortunately, only the very, very rare tumor is adequately treated with this charge.

Chemotherapy: An extraordinary compendium of chemotherapeutic agents is under constant development at present -- thus, the large number of new protocols seen every year. Agents that cross the blood:brain barrier are logical candidates for a future cure. Agents that don't naturally cross the barrier can be helped along with what is know as Blood:Brain barrier disruption, usually with agents such as mannitol or leukotrienes.

Immunotherapy: The future holds great promise for immunotherapeutic approaches. At present, the combination of the impenetrability of the Blood:Brain barrier, the immunologic isolation of the brain from the rest of the body, and the larger size of immunologic molecules and cells has prevented the effective marshalling of the body's best defense system to any significant degree.



What To Choose

Firstly, speak at length to your neurosurgeon and neuro-oncologist. Try to concentrate on local, tumor bulk reduction as the first move, to be followed later by whatever is both aggressive and capable of treating the whole brain. As there are so many protocols, find out who in your area has a specific interest in brain tumor therapy, and go with what they are best at. Alternatively, one can consider going to another locale for treatment.

Most of all, feel comfortable with your choices, and go with them. Almost always, within weeks of learning the diagnosis, people seem to come out of the woodwork with all kinds of other and/or alternative therapies. Such suggestions invariably lead to second guessing and further worry during difficult times. If you realize that you have already researched pretty well, remain confident with you original decisions, at least for the duration of the initial course of therapy. After that, go with what works, when it does work. Always remain ready to change therapeutic course, if it is very clear that a specific choice is not proving successful.

Planning Your Surgery

In most instances, the combination of CT Scan and MRI are more than enough to plan surgery. However, there are times when further workup is needed to either guide the surgeon or to accurately localize areas of "eloquent" brain that the surgeon must avoid. "Eloquent" refers to those areas which control speech, motor functions and senses.

The simplest "localizing" scan is done by CT or MRI, and either a small metal marker (CT), or vitamin E capsule (MRI), is positioned directly over the superficial most point of tumor, or away from eloquent brain tissue. The skin is then marked and the surgeon is given a sense of security that he is in exactly the right spot. This method is particularly good for superficially placed tumors. In the operating room, the surgeon can then use real time intraoperative ultrasound to "see" the tumor below the surface prior to incising the brain.

With the age of computer technology, computer-assisted, 3D-sterotactic localizing and guidance devices have been devised. These have been extremely helpful for tumors with complex shapes and/or deep-seated locations. It is kind of like having an assistant who is smarter than the surgeon in the operating room -- a wonderful asset.

Areas of brain to be avoided ("eloquent" brains, for example) can be localized prior to the operation by a number of techniques. These include EEG brain mapping (either directly on the brain with grids, or with a computed analog system), as well as encephalomagnetic studies, non-invasive, talk, and the eloquent brain lights up), PET scanning, and at times SPECT scanning.

Low-grade Primary Brain Tumors

These include astrocytoma, grades I and II, oligodendroglioma, ependymoma, and a mixed cell tumor called the ganglioglioma. Remember that benign is not always benign. When a tumor appears to grow with some speed, the tumor should be viewed in a different light and a more aggressive approach must be taken.

One approach is to observe lowgrade tumors after the initial surgery or brain biopsy has been completed; it is necessary to assess their growth potential. Individual tumors, like people, seem to have personalities of their own. Different tumors behave differently.

Why do a biopsy, if surgery does not "cure" the tumor? Why not just follow the MRI scans over time to assess the growth potential of a particular suspected lowgrade tumor? The answer for these questions lies in the fact that occasionally a surgical cure is possible, depending on the diagnosis and location of the tumor. (e.g. microcyctic cerebellar astrocytoma, certain gangliocytomas, pleomorphic xanthoastrocytoma, "hamartomas"). Therefore, the biopsy information is of great importance.

Another approach is to treat all low grade tumors with surgery and/or brain biopsy and radiation therapy. However, the jury is still out on the effectiveness of radiation for these tumors, especially the lowgrade astrocytomas. Meanwhile, in long-term survivors, it has been shown that both malignant astrocytomas and meningiomas can actually be induced by radiation.



Primary Tumors in Children

The most common tumors in children are the astrocytomas and medulloblastomas. The medulloblastoma is one of the primitive cell tumors of children, as are another class of even more primitive tumors, the Primitive Neurectodermal Tumors (PNET). Some tumors of children (such as the microcystic cerebellar astrocytoma, and the subependymoma) may be truly benign, while other astrocytoma subtypes (including the optic, chiasmatic and hypothalimc astrocytomas, as well as some of the brainstem astrocytomas of children) may grow slowly but inexorably.

In children, the need for more than just whole brain therapy is mostimportant for craniospinal therapy. In children, the primitive tumors tend to "shed" tumor cells into the fluid spaces in and around the brain and spinal cord, causing distant tumors to grow.

Meningioma

The meningioma is the neurosurgeon's "friend" and often his most enduring challenge. For both the physician and patient, this tumor carries a true tag of benign. It also carries the possibility of "cure" in approximately 80% of cases. Thus, the long-term outcome for a patient with this tumor is a direct function of the skill and assiduousness of the surgeon who removes it.

Elsewhere in the Brain Surgery Information Center's Primer on Brain Tumor Biology, it was mentioned that "benign" often does not really mean benign. Be assured that in this case, the tumor really is benign.

As mentioned earlier in the Primer, each type of brain tumor arises from a specific cell type. The cell of origin for the meningioma is call the arachnoid cap cell, found on the surface coverings (called meninges) of the brain in the paccionian granulations. These serve as the one-way valve system between the water system of the brain and the veins that drain from the brain to the heart.

Interestingly, these tumors have an embryologic relationship with cells found in the muscle layer of the utereus. In fact, it is exceedingly difficult for the pathologist to distinguish the meningioma from the fibroid tumors of the utereus under the microscope. Also, they share the characteristic female hormonal receptors (estrogen and progesterone) on their cell surfaces. This characteristic has lead to the testing of anti-estrogen receptor agents, such as tamoxifin, as a growth-inhibiting agent in these tumors. Clinical studies to date have failed to provide siginificantly positive results.

Meningiomas are rarely malignant in their behavior. But when malignant, meningiomas grow rapidly and are destructive; they are quite difficult to treat, and recur oftentimes in less than a year after surgical removal. They are also difficult for the pathologist to diagnose under the microscope. Probably the only finding that correlates well with the diagnosis is that of numerous cells seen in division ("mitosis"). The pathologist may occasionally speak of brain and skull invasion, cells with an abnormal appearance, or other bizarre findings, however none of these completey fit the diagnosis. Ultimately, the diagnosis is determined by the activity of the particular tumor over time.

A cousin to the meningioma is the hemangiopericytoma. The cell of origin for this tumor is the perivascular pericyte (located around blood vessels). Although very similar to the benign meninigiomas, these tumors tend to recur with great rapidity (less than one year) and frequency. Some physicians classify these tumors with the malignant meningiomas.

Brain Tumors in Children

"I am truly sorry, but your child has a brain tumor..."

The World of Childhood Brain Tumors has no "Welcome" sign leading into it.

No matter what anyone says to minimize the situation, this statement is the most painful sentence a human can hear. The combination of fear, shock, pain is much to bear.

"To see such innocence, so roughly shaken by this terrible trial, at such a young age, is nothing short of incomprehensible." I still hear this sentence, uttered by a visibly shaken parent. Instead of my becoming more routine and distant, the visceral terror that it engendered in me (the supposed all- knowing physician/advisor), the delivery of such information has grown more and more difficult, even personal. I watch my own small children grow and develop. As a physician, one realizes more than ever, there is no place for impersonal behavior when caring for the children who are afflicted by a brain tumor, benign or otherwise--their families as well. No amount of experience or training can help one to ease or minimize the situation.

When we discuss special areas such as:

• Outcome: Does "excellent long-term results" mean a ten-year survival for a 3-year old-- your child living long enough to be frustrated by death at the age of thirteen? We parents think only of 50 and 60 year plans. Five and ten-year plans are unacceptable. We want to know that our grandchildren will not live to see their parents die at a young age.
• Quality of life: Does that mean that a 5-year old child will have no hair, be skinny and slow to walk and play with his friends and classmates? How can we parents bear to live through the process of trying to give our child a childhood instead of a world of I.V. tubes, doctors who speak of life-and-death, hospital corridors and toys that our children will never play with?
• Doctors: Who are they? Can we do anything to keep them human, warm, and caring for our child? How do we deal with our own resentment for the fearful news, difficult therapies and their human frailty? How do we keep our child happy to see them? Most children cringe at the mere mention of visiting a doctor-with-a-shot-to-give, or a visit to the dentist with his drills and instruments?
• Hospitals: How do we keep these innocents away from such large and frightening monoliths?
• We parents: How can we possibly bear all of this without frightening our little, loving child?
• Hope: Yes, there IS hope! God and goodness are your guide. Your child is truly a precious gift. No matter what cards we are dealt, a child's joy and innocence are somehow never lost. In the worst of times, a child's pain often becomes the parent's teacher. And, when we expect the best for our children, we often get it despite all odds.

THE BIOLOGY OF CHILDHOOD BRAIN TUMORS

Pediatric brain tumors are different

Most frequently, they come from "young" cells. These are cells that are still developing ("immature" or "primitive" cells) and have not reached full maturity. They are developing at the same time as the child is developing. If one looks at the way a normal cell matures from its very beginning as a "primitive" brain cell (a precursor) through its stages of normal development, towards becoming an adult cell type, one can start to understand the logic of the progression of tumor types in children.

A diagrammatic representation of the manner in which brain cells develop from the embryo to the adult is under constructiion. It will be posted soon.

For every normal cell type, there is a corresponding tumor that can arise from it. Thus, there is the primitive neurectodermal tumor (PNET), the medulloblastoma, the astroblastoma, the neuroblastoma, the astrocytoma, the gangliocytoma/neurocytoma, the ependymoma and so on.

There are also other unusual tumors such as the teratoma, the pinealblastoma, the esthesioneuroblastoma, etc. There are also other tumors thay come from non-brain origins such as the pituitary tumors, teratomas, meningiomas, the skull bone tumors, and blood vessel tumors such as the hemangioblastoma or cavernous angioma.

Children commonly have brain tumors such as the PNET, medulloblastoma, various embryonic tumors and unusual tumors of the developing brainstem, hypothalamus and optic nerves (juvenile pilocytic astrocytomas, teratomas, etc.) There are variations of these tumors and they are rare as well as difficult to understand.

Parents and children should ask as many questions as possible. The questions can help reach level of comfort confident that the problem is clearly comprehended. Knowledge of the expected and the potentially unexpected will allow you to guide your child through the process of battle against their brain tumor. No matter how harried, tired or busy your surgeon and doctors might seem, it is important to understand the problem at hand fully. This will make the efforts of all involved more effective. More often than not, knowledge helps us cope with the developing situation better.

The most important point is that some of these tumors hold the promise for a true and complete cure! There is nothing more satisfactory than the complete removal of a dreadful sounding cerebellar microcystic astrocytoma or a hemangioblastoma. Families soar from the depths of despair to the heights of sublime elation when the smiling surgeon comes to the waiting room after a difficult surgery. The surgeon may not look tired at all. The smile-on-his-face says that he has just had the privilege of completely removing a tumor!

MEDULLOBLASTOMA

This tumor is probably the most common tumor of children. It arises from one of the "junior" cells of the developing brain, called the medulloblastoma. This tumor almost always grows in the middle of the cerebellum (the balance part of the brain, in the back, behind the brainstem). More often than not, small children are found to have the tumor only after it has caused secondary problems relating to blockage of the normal flow of cerebrospinal from the ventricles to the drainage system located along the outer surface of the brain (Obstructive Hydrocephalus). This results in headaches, visual problems, and decreased alertness. Often, parents will notice "sundowning", (the eyes are "stuck" in the downward gaze position) of the baby's eyes, due to local pressure on one of the brain's centers for eye control.

EPENDYMOMA

The ependymoma arises from the cells that line the internal surfaces of the brain. These cells line the fluid spaces of the brain (ventricular system) and are relatively few in number. Some of these cells are quite specialized, having little frond-like protruberances that move the cerebrospinal fluid as it permeates into the brain from the ventricular system and back again.

These tumors are rare. They are usually found on the internal surfaces of the brain and spinal cord, such as the fourth ventricle of the brain (in the back, inside) and within the central canal of the spinal cord. Occasionally they grow just beneath the surface of the lateral ventricles (called "subependymoma").

Although these tumors are capable of malignant behavior, they are almost always benign. Surgical removal often leads to a cure, especially when the tumor arises right from the surface to the fluid spaces of the brain and grows into the ventricles, an "exophytic" growth, allowing for complete removal.

If you or yours has this tumor, be confident that your future holds promise.

CEREBELLAR ASTROCYTOMA

This tumor is quite cureable. The small cyst version is one that, when surgically removed, is gone for good. Forget about all the fears, just thank God that your child will do well. Even if the MRI or CAT scan shows a large cyst with surrounding tumor or a tumor "nodule" in the wall of the cyst, the surgery can go well.

When the tumor is the more aggressive type, the outcome deplends on the grade/size of the tumor.

TREATMENT OF CHILDHOOD BRAIN TUMORS

The treatment of these tumors usually include a combination of approaches, each tailored to deal with the problems that children are presented with:

1. Surgery:- In some cases the definitive treatment is surgery. In most, however, surgery serves as a temporizing measure that will keep a child out of trouble for long enough to get through definitive therapy that will hopefully eliminate of the tumor. Brain surgery is usually the easiest part of a child's treatment.
2. Shunting:- Quite often (e.g. medulloblastomas) childhood tumors present the blockage of the fluid spaces of the brain, (obstructive hydrocephalus). In Shunting, a thin silastic tube (the shunt) is placed into the fluid spaces of the brain, passed under the skin into the child's tummy where the fluid is absorbed.
3. Chemotherapy:- Unfortunately, chemotherapy is the hard part of brain tumor treatment. It is only required for the more aggressive tumors. As a rule, chemotherapy should be even more aggressive than the tumor itself. The trials which are imposed both on the child and parents are legion. Bravery and an unremitting attitude of hope are required by all involved.
4. Radiation:- Because the developing brain of a child is so very sensitive to radiation therapy, it is deliberately limited. The irony of effective radiation therapy is that when it works well, the brain damage it causes might exceed that done by the original tumor. More often than not, your doctor will recommend that if any radiation is to be given, it should be held off until the child has grown older and the brain has sufficiently matured.

The Good News is that REAL HOPE exists. Long term results are becoming more and more common, some children surviving fifty years and beyond. This has become especially true with the wonderful improvements in chemotherapy and surgical techniques. The promise of cures for difficult tumors is becoming a reality to more families than ever before.

Subdural Hematoma

A TYPICAL SCENARIO:

The headaches she had been complaining about persisted for a few weeks, but no one worried. Then, she awoke one morning with slurred speech and a wobbly gait. Now all were worried.

The family doctor was called; he recommended a CAT scan of the brain. After the scan, came the call: Go to the hospital right away! She has a subdural hematoma. We question Why.

She had hit her head.

When?

No one in the family ever saw that, and she never said anything. She was sleeping last night safe and sound in her bed. How could she have hit her head while she was asleep?

It didn't happen last night. It probably happened weeks ago. In fact, she probably didn't think much of it then. It may even have been a minor bump perhaps bumping her head on the car roof as she tried to get into the car during that rainstorm a few weeks ago.

Could that have caused all of this trouble?

This is the world of the subdural hematoma.

HOW DID IT HAPPEN?

One of the many interesting things about the brain is that the cells that we are born with are all that we ever get to work or play with. Actually, a newborn has more brains than a fully matured adult!

The brain does not reproduce itself. And, as we age,that brain we were born with gradually shrinks.

On the other hand, the skull, once fully grown, never gets smaller. The result is that our heads become very much like walnuts: seeds dehydrate and shrink within the firm shell. You can hear the kernel shake as you try to open the shell.

As the brain shrinks, it too pulls away from its covering shell of bone(our skull); the intervening space is replaced by brain fluid (CSF. Sorry, no rattle).

At the same time the blood vessels which come from the brain and extend up into the skull become stretched, like rubber bands. When they reach a certain limit, even a minor bump to the skull can cause them to snap and bleed into the subdural space between the inner skull surface and the brain.

With the body's excellent blood-controlling mechanisms at work, the first few "episodes" may go unnoticed, since there is plenty of room for the blood. However, with repeated episodes, a critical volume is reached, and the brain suffers with a compression.

This is the time that the lady awakens with a noticeably malfunctioning brain--slurred speech and wobbly gait.

More often than not, these chronic Subdural Hematomas are not fresh clots, but rather liquefied, old blood mixed with some fresh blood. Thus, they can be easily drained by a very small hole in the skull. In fact , the earliest operations known to man were done for this reason. More than 3,000 years ago, many peoples including the Incas of South America and the Sumerians of the Middle East performed these operations called trephination, in the hopes of expelling evil spirits from the brains of men they felt were possessed. Many such skulls have been found at archeological digs the world over. These operations often were successful even then.

OTHER CAUSES

• Major Trauma


By far the most common cause of a subdural hematoma is severe brain injury after a car accident or a fall from a great height. These traumatic subdural hematomas are always associated with considerable brain damage, and occur immediately after the injury. These injuries will be further addressed under the heading of Brain Injury(under construction).

• Spontaneous Acute SDH


Occasionally an artery on or near the surface of the brain will burst, causing a very large and emergent subdural hematoma to develop. These are due to vascular malformations of the brain (e.g. aneurysm, AVM, dural AVM), containing a threat for future bleeding. Because of the high pressure (and therefore volume) and rapid expansion of these SDH's, the patient is most often in serious trouble, requiring emergency surgey be performed.

Intracerebral Hemorrhage

For the families of intracerebral hemorrhage victims, the following scenario will sound familiar, almost like a dramatic scene from a TV movie.

It begins at a wedding reception. Grandfather is dancing with the bride, his beloved granddaughter. Everyone is having such a good time! He is returning to his table to be with Grandmother when he emits a cry and collapses. Loved ones rush to his aid and, for a moment, he seems to be coming out of it. Then, all notice his speech is not normal; he cannot get up, even though he tries. The right side of his body isn't working at all.

An ambulance rushes him to the hospital. Everyone looks worried. In the emergency room, the CAT scan tells the physicians that he has suffered a serious "Brain Attack"/Stroke. A tiny blood vessel has burst and bled under high pressure. It leaves a path of destroyed brain tissue in its wake and further threatens surrounding brain tissue with more damage, as the mass effect of the large volume of blood compresses the surrounding brain tissue.

The hospital learns of his high blood pressure history.

This is the awful world of the hypertensive "Brain Attack."

EXPLAINING WHAT HAS HAPPENED

The brain is an "end organ." It is also the most energy-hungry organ in the body. Because of these two factors, it constantly demands a disproportionately large percentage of the blood supply from the heart. The brain weighs about 5% of the body's total weight, but constantly uses more than 20% of the body's blood supply to survive. It has both "old parts" and "new parts." As the human species evolved over the ages, some of the less sophisticated parts of the brain remained unchanged; other parts have been modified as humankind progressed along its evolutionary path. Among these unchanged brain parts are the very simple, thin-walled blood vessels that supply one of the oldest parts of the brain, the basal ganglia. This area of the brain is made up of the neurons responsible for things like control of coordination and central relay centers for sensation. (Globus pallidus, thalamus, etc. are parts of the brain which are affected by Parkinson's Disease). Of all the vessels in the body, these are the least prepared to handle chronic, increased blood pressure. At the same time, they are responsible for carrying a larger amount of blood to a very vital area, at relatively high pressures. Thus, over the years, they can develop microscopic outpouchings called Charcot aneurysms. These are not at all like cerebral aneurysms which cause subarachnoid hemorrhage (SAH). When the tiny Charcot outpouchings burst, blood enters into the brain at very high pressure, destroying all tissue in its path.

Other Kinds of Intracerebral Hemorrhages

Other hemorrhages include those arising from: arteriovenous malformations, unsuspected tumors, brain vessel diseases due to infection, degnerative diseases such as amyloid angiopathy, drug useage (intravenous, amphetamine or cocaine usage), or blood thinner therapies (e.g. coumadin or heparin treatment for heart disease).

Changing Times, Changing Therapies

Until recently, ICH had been treated with watchful waiting, except for those cases where the size of the hemorrhage absolutely demanded surgery. The brain will eventually absorb the blood over time (three weeks to 2 months). With the advent of improved surgical techniques, localizing imaging capabilities, and better understanding, a move to early surgical removal or decompression has been the new trend.

Better Understanding

Even if the high pressure blood hadn't cut a path of brain destruction, the shear mass of the blood within the brain and the tight confines of the skull could be responsible for continuing damage to surrounding brain tissues. In this surrounding brain (called the pneumbra), the local pressure of a blood clot may be greater than that of its blood supply, causing the brain cells in that area to die off. To minimize further destruction, therefore, it makes sense to reduce the local pressure by decompressing such brain tissues through the removal of most of the blood clot.

Also, it is now known that blood becomes toxic. Blood cells are tiny packages of chemicals that the body is normally protected from by the cell membranes that contain them. As the blood cells within a clot die, they swell, burst, and release toxic chemicals which are capable of damaging the surrounding brain. The new approach to this problem is to eradicate such toxins BEFORE they are released.

Improved Imaging Capabilities

No matter how deep and unseen the blood clot, new imaging techniques allow the surgeon to target and see exactly where he needs to go when removing a blood clot. Sterotactic machinery and real-time intraoperative ultrasound guidance systems have helped tremendously, practically eliminating the downside of surgery.

Improved Surgical Techniques

Smaller openings, better surgical accuracy, improved lighting, the simplicity of needle aspiration techniques, and the usage of surgical hemostatic agents (that prevent post operative bleeding) all lessen the danger of brain surgery for ICH. It is now reasonable to remove any and all brain hemorrhages of significant size very soon after the patient has arrived at the hospital. This new approach has become a part of the "acute care" treatment application to Brain Attack victims. Over the past few years, the medical community has come to consider ICH a near emergency and treated as such. Your neurosurgeon or neurologist will explain "acute care" treatment early, in the hopes of salvaging undamaged brain when possible.

Delay or Hold on the Surgery

Factors that might delay early removal of an ICH include: stabilization of blood pressure or other medical conditions (e.g. diabetes, clotting abnormalities, liver or kidney failure, heart problems etc.); reversal of medications that prevent blood clotting (e.g. coumadin or aspirin), or Amyloid Disease of the brain. Most often, surgery is not helpful in these instances, and future blood clots could also occur after a relatively short interval. Another condition calling for surgical delay could be the extremely poor neurologic state of the patient. Even a small hemorrhage in the wrong place (such as the middle of the brainstem) may be associated with such a poor outlook that surgery would not be of help, or could even result in further damage.

Cavernous Hemangiomas

Also known as "Cavernomas" and "Cavernous Malformations."

These lesions have been found with increasing frequency over the past few years because of the incredible accuracy of MRI scanning. They arise from the tiny vessels that separate the arterial system from the venous system of the brain. There is some controversy as to whether the cavernomas are true vascular malformations or very slow growing tumors of capillary blood vessels. They are characterized as truly benign lesions, and can be completely removed and cured by surgical removal. However, as many of these lesions are found coincidentally, they are often left alone if no evidence of hemorrhage is present at the time of the MRI study.

They may induce seizures; occasionally, their removal leads to seizure control when medical therapy fails. When they are noted along with hemorrhage, they most often do not cause neurologic devastation, as do brain aneurysms and AVMs. The reason for this has to do with the very low vascular pressure within these malformations.

Consequently, the usual volume of hemorrhage is small, causing temporary deficits that generally improve (not completely). We now know that the cavernomas do grow slowly over time, and that once they hemorrhage, they tend to do so again. Each subsequent hemorrhage is usually followed by a stepwise deterioration in neurologic function, causing the patient to lose something with each bleed. When they are found in the brainstem, the most compact and important part of the brain, cavernomas may represent a threat to a patient's life. As might be expected, even a 5cc hemorrhage into the jam-packed area of the brainstem may cause difficulty swallowing, double vision, loss of facial function, and even loss of consciousness.

TREATMENT OPTIONS

No Therapy

When found incidentally, with no prior history of problems related to the discovery of one of these lesions, most physicians will follow them with serial MRI scans over the following years. Small lesions in difficult places are often left alone, even if they are responsible for seizures. The same is true when the risk/benefit ratio for surgical removal may not allow the surgeon to go ahead.

Surgical Removal

Ironically, the best time to remove these lesions is soon after they have hemorrhaged. The reason for this is that the hemorrhage does some of the surgeon's work for him, separating the lesion from the surrounding brain. This makes the removal easier, and also limits some of the potential downside of surgery. Patients who have lesions that have bled previously, but not recently, are occasionally told to wait for their next hemorrhage before considering surgery, usually due to the difficult location of their cavernoma. When easily accessible, large, responsible for serious hemorrhage or for uncontrollable seizures, surgical removal is the way to go. Once removed, these lesions are cured.

Difficult to access lesions require 3-D computer image guided sterotactic surgical systems. In cases of patients with multiple cavernous malformations (these may run in families), only symptomatic or dangerous lesions are excised. A serious problem arises when a pregnant woman has multiple cavernomas. These present a real challenge, especially if the mother has had previous hemorrhages.

Radiation Therapy

There is no evidence that radiation therapy does anything for Cavernous Hemangiaomas. Focus beam radiation (e.g. Gamma Knife) is currently being recommended by some physicians; however no long term results (including radiation damage, malignant tumor induction etc.) are in as yet.

Arteriovenous Malformations (AFM)

Arteriovenous malformations are masses of abnormal blood vessels which grow in the brain. They consist of a blood vessel "nidus" (nest) through which arteries connect directly to veins, instead of through the elaborate collection of very small vessels called capillaries. Some people are born with the nidus, but as the years go by, it tends to enlarge as the great pressure of the arterial vessels can not be handled by the veins that drain out of it. This causes a large collection of worm-like vessels to develop (malform) into a mass capable of bleeding at some future time. These malformations are most likely to bleed between the ages of 10 - 55; after 55, the chances of bleeding diminishes rapidly. Before 55, the likelihood of hemorrhaging is betweeen 3 and 4% per year (with a death incidence of about 1%). Once an AVM patient has hemorrhaged, the risk of having another one might approach 20% during the first year, and gradually lessen to about 3 - 4% over the next few years.

AVM s can occur in any area of the brain, and may be either small or large. When they hemorrhage, they usually do so with a limited amount of blood, unlike the hypertensive hemorrhages of other stroke patients. Loss of neurologic function depends on both the location of the AVM and the amount of bleeding. Many patients have very small hemorrhages, often multiple. They may display convulsions before even knowing about the presence of an AVM. Some patients suffer with headaches, often unrelated to the AVM which are usually found with a CT scan or brain MRI. In rare instances, children are born with large AVM's and are found to have heart failure because the malformation makes the heart work beyond its capacity.

These lesions are surrounded by a very discrete layer of abnormal, nonfunctioning brain tissue, thus allowing their removal with relative safety to the surrounding brain. This factor is of the utmost importance to the brain surgeon, who can take advantage of this natural separation between normal brain tissue and the abnormal vascular malformation.

TREATMENT OPTIONS

Radiation

If there is a very small AVM, and it is deep seated in the brain, the patient is fortunate. It is possible to give focused beam radiation to the malformation, and avoid surgery. Within two years the malformation will most likely disappear.

Embolization

Larger malformations may be made more surgically manageable with a technique called embolization. With this procedure an angiogram becomes a therapeutic tool. The interventional angiographer is capable of filling the malformation with agents which help decrease the blood supply to the malformation (coils, glues, plastic spheres, balloons, etc). This makes surgery easier in some cases. The technique has been used as the primary treatment as well, and has apparently been successful in some cases.

Surgery

Perhaps surgery is still the best way to go if the decision has been made to do something to eliminate the AVM for good. Surgery cures these lesions by totally removing them, thus disallowing them from ever recurring again. The author's personal bias (quite strongly held) is that most AVM's are best cared for with surgical removal. Even with patients who have large and complex AVM's, surgery provides the cure when the malformation is completely removed.

Today, with the assistance of BrainLab's most sophisticated equipment and computerized techniques, an AVM removal has been greatly facilitated. Here are two phases of an AVM removal:

• AVM Removal Part 1

• AVM Removal Part 2

Leave It Alone

Some lesions, because of their size, location or behavior are best left alone. In these cases, your surgeon's judgment is of the utmost import.

In other cases, courses of treatment may be determined by the age or medical condition of the patient. An example might be that of an AVM being found in a 70-year old woman suffering headaches after her heart surgery, having had no prior history of problems relating to the malformation. Another example might be the case of the 52-year old businessman with a very large and complex AVM located deep in the brain, involving the vessels that drain to the brainstem and/or speech areas of the brain.

Aneurysm Surgery

Stroke is the ultimate "Brain Attack." It can strike the young, healthy, productive head of a household during a soft, shared moment with a spouse -- anytime. Nothing is more frightening. One might hear: "I'm having the worst headache of my life!" Or, "Oh, my neck is so stiff!" Then the victim might vomit, perhaps have a convulsion which could leave them comatose and all bystanders truly frightened.

In the emergency room even the doctors look worried. The CAT scan shows "blood around the brain," something doctors call a "subarachnoid hemorrhage." There could possibly be other problems, such as a blot clot in the brain itself ("intracerebral hemorrhage) and/or something called "hydrocephalus" (water on the brain, building up after blood cells have gradually clogged, the brain's drainage system).

There is lots to be done, and in a very short time frame. Backtracking a bit, it is important to get an instant education on the "Brain Attack."

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Some basic questions:

• What is a brain aneurysm?
• How serious is the problem?
• How did this problem come about in the first place?
• Why this specific person?
• What are the problems at hand?
• Who can do what? Etc. Etc. Etc.

The Aneurysm

The brain is interesting for many reasons. Of prime importance, the brain uses, pound for pound, more energy than any other part of the body. It must be guaranteed just the right amount of blood for every instant of its life in order to survive and function well. Of all of the blood that the heart pumps, the brain needs the most. It weighs about 5% of the body's total weight, yet it demands and monopolizes about 20% of the volume the heart puts out. The blood vessels at the base of the brain (these are the largest, and "smartest" of all vessels) have the capability to control -- even commandeer -- blood to supply the brain as conditions demand. When we lie down, these vessels constrict automatically to prevent the brain from being flooded with an over supply. And, when we jump up, these vessels have the James Bond-like buttons built in, to make sure that the heart not only pumps harder, but also that the other blood vessels open up enough to handle the increased volume required by the brain. Thus, these blood vessels have three things that are needed for survival:

1. Elasticity that allows them to keep their shape (like socks)
2. "Smooth muscle," that can be relaxed or tightened as conditions require
3. An electronic feedback system (i.e. sensors and nerves) that makes everything work.

People who grow aneurysms have an inborn problem with the elasticity part of these blood vessels. The elastic layer is not formed properly (being randomly, rather than regularly organized). This weaker part of the blood vessel begins to bulge and balloon over the years. It is this bulge which is actually called the "aneurysm." It develops in places where the pressure is greatest -- usually where the vessels divide into multiple routes. It enlarges and enlarges, and enlarges further still. Eventually, its chance of "popping" like an over inflated balloon becomes real. When the local blood pressure exceeds the strength of that vessel's weak point, the danger of rupture is at hand.

In these people, over the years of their lifetimes, and at the points along these vessels where the defect in the elastic layer exists, a gradual bulge and finally a balloon develops in places where the pressure is greatest (usually where the vessels divide). Over time, the result is a little (and ever-enlarging) balloon called an "aneurysm." And, as for all balloons, the chance of "popping" becomes real when the local blood pressure exceeds the strength of the balloon's wall at its weakest point.

When they do pop, a surprisingly small amount of blood escapes, due to the efficiency of the blood's clotting system. It's difficult to imagine, but only 5 to 10 cc's of blood could be responsible for causing such disastrous consequences! In those people whose aneurysms bleed much more, death occurs even before they get arrive at the hospital.

"Brain Attack"

1/3rd of people with ruptured aneuryms die before they get to the hospital.

1/3rd die after they get to the hospital.

1/3rd survive after they get to the hospital. Of these, 40% end up with neurological problems that make life difficult.

Let's look at the problems that occur after arrival at the hospital. Then, the all important "how-to-prevent and/or fix" them as they arise. First...

Truth and Consequences Solution

Hemorrhage? Statistics show death rate of 60%. Fix the aneurysm early

Hydrocephalus? An insult added to the injury Place a "shunt."

Vasospasm? The 1/3 who die after coming to the "Triple H" therapy

hospital

Preventing Second Hemorrhage

In the emergency room, the doctors will try everything to prevent the small clot at the rupture point in the aneurysm from dissolving or becoming dislodged altogether. They will concentrate on three things:

• * Keeping the blood pressure spikes form occurring again. (Give blood pressure medications, prevent anxiety attacks, keep the environment calm).
• * Giving drugs to prevent the clot from dissolving ("Amicar" can only be used for the short-term, because it will cause blood clots in the legs and lungs to become a problem.)
• * Avoiding convulsions (drugs such as dilantin, phenobarbitol).

Once the patient is stable, and the full support team is assembled, the definitive procedure to prevent re-bleeding can be undertaken: The Operation.--

The operation has as its aim the "clippings" of the aneurysm at the base of its neck (just like tying off a balloon), so that it is eliminated from the blood circulation of the brain.

The aneurysm can be seen by a number of techniques, the most reliable and accurate of which is an angiogram. A catheter is passed into the vessels at the base of the brain and a radio-opaque dye (called contrast) is injected while X-Rays are taken. This study sets up the road map of the blood supply to the brain, and brings the anatomy of the aneurysm to light. Other, less invasive ways to do angiography include MRI scanning (MRAngiography) and the Spiral CT Scan using intravenous rather than intraarterial contrast. These studies give a 3-D character to the images, making them particularly helpful to the surgeon.

Aneurysms can also be cured by other techniques in selected cases. A revolution (some call it a rapidly expanding evolution) is occuring in the technology of "interventional radiology," allowing doctos to fill aneurysms with metal coils, glue, balloons, and even "stents."(JR: What is a stent?) There may well be a future in which surgery will become the other option, if such rapid progress brings the hoped-for results.

The innumerable improvements and in microsurgical technology and techniques, indicates that the least of the patient's problems is surgery. Surgical morbidity and mortality is arbout 2 % (but up to 15% for the most difficult of aneurysms), yet, it is the most frightening part of the whole story. Surgery is, in point of fact, the least threatening treatment. Patients and their families always look at the surgeon strangely, when he says, "Surgery is the easy part overall! Don't worry so much about that part of it; much more difficult hurdles await during the next few weeks of therapy.

Preventing Hydrocephalus

20% of patients will develop (brain water) clogged CSF outflow passageways, causing what is called "communicating" hydrocephalus. Initial treatment might consist of the placement of a "lumbar drain" (i.e. an ongoing spinal tap for 5-14 days.) If the hydrocephalus persists, a CSF shunt (a tube, draining CSF from the ventricles in the brain, tunneled beneath the skin, into another location such as the chest or belly) could be placed for permanent drainage.

Preventing or Fighting Vasospasm

The real killer, after re-bleeding has been prevented, is vasospasm. Vasospasm can easily cause second strokes, when a brain blood vessel becomes so constricted that blood is prevented from entering the brain altogether.

When an aneurysm ruptures, blood escapes and does not go into the brain, but rather around it. The brain, like a permanent embryo, is filled with and surrounded by water. When blood gets trapped there, the red and white blood cells die and eventually disintegrate within 2 to 5 days. Imagine that each blood cell is nothing more than a simple bag containing a complex variety of chemicals, some of which are very toxic to the "smooth" muscle layer of the blood vessels arrayed around the brain. When these vessels are bathed by such a combination of toxins, their "smooth" muscles contract, causing the vessel to become so small that blood is prevented from traveling to the brain tissue beyond.

Despite more than thirty years of painstaking research into the problem, only three clinical treatments appear to be effective in concert: the so-called "Triple H" therapy.

• * Hemodilution -- lowering blood viscosity (thickness, like thick soup, causes increased friction among blood cells, thereby reducing blood flow and threatening blood supply), reducing its minimum ("hematrocrit") to around 32. High blood viscosity is extremely dangerous in the face of potential vasospasm.
• * Hyperdynamic State -- Increasing the amount of blood pumped to the brain by the heart ("cardiac output") appears to keep the "pipes" open by maintaining a continuous head of pressure in the system, and thereby preventing vasospasm. A cardiac output is around 5 liters/minute (JM: Is this the normal rate, or the rate desired to be achieved ?). With a combination of intravascular volume expansion (lots of I.V. fluids) and heart pumping medications (such as "dobutamine"), such a hyperdynamic state can be achieved.

Predicting Outcome

Let us assume that the patient has arrived at the hospital, been seen and evaluated by the doctors. They have news for you, and your decisions will depend on what they tell you. The doctor can predict with a fair degree of accuracy, what the future holds, even in the best of circumstances. He will count on at least two factors: (1) the Hunt-Hess score, and (2) the CT Scan grading scale. He will then factor in such things as added problems, such as hydrocephalus, general medical condition, age, and try to offer a realistic outlook for the patient.

Hunt-Hess Score - a way to measure to status of the patient after arriving at the hospital. In general, patients with scores of I - II do well, while others do not. The scores are:

• Grade 0: Only the morbidity of surgery and that of natural history apply.
• Grade I : After a small SAH, the only symptom is headache. The patient is neurologically normal.
• Grade II: The patient is not all there. "Goofy" is a good way to describe this patient.
• Grade III: Not only "goofy," but the patient has specific weakness of an arm, a leg or the face.
• Grade IV: Severe neurologic deficit. This patient has great trouble.
• Grade V: Vegetative state. A most horrible outcome.

Stroke / Brain Attack

Preventable, costly to the entire nation, this brain ailment is the third leading cause of death in the USA. The statistics on strokes are impressive:

* 150,000 deaths per year.

* Total cost to society is more than $30 billion per year in medical costs and lost productivity.

* It is the leading cause of disability.

* Strokes are the most preventable of all catastrophic conditions.

* It affects people of all ages; its incidence increases, however, with aging.

* Strokes reach every walk of life, every ethnic group.

* Brain surgery can be a preventive technique.

You can self-administer the Brain Surgery Information Council's test/guide which will aid you and your physician in an overall evaluation of your "stroke potential." (We're going to offer an evaluative, inter-active test concept.) The inquirer can take the test, get an evaluation, confer with his physician, or call us. Early surgical interventive techniques are today's front line of defense against many of these "Brain Attacks."

Types of Strokes:

*Ischemic Strokes - account for about 84% of all strokes. They occur when the blood supply to a portion of the brain is interrupted. The thrombotic kind stems from a clot which has built up in the cerebral artery; embolics result from a circulatory blockage to a portion of the brain which can be traced elsewhere -- most frequently from the heart or the cervical portion of the carotid artery.

* Hemorrhagic Strokes - make up the remaining 16% of these calamities; they are caused by bleeding in the brain space (intracerebral) or between the brain and the skull (subarachnoid). These kinds of strokes are more dangerous and life-threatening than the Ischemic strokes.

Symptomology

Don't over apply the following symptoms to your own condition. Headache is perhaps the universal symptom. They are often described as "splitting," "migraine," "the worst of my life," and are almost always present at any stroke incident. A stiffness of the neck is another indicator. Frequently, an accompaniment of nausea or vomiting can confuse the condition with a viral illness. If there is severe headache with a loss consciousness (no matter how brief), investigation of stroke prevention procedures should be seriously considered...and quickly.

Other symptoms, less frequent in occurrence, might include convulsions, coma, loss of hearing or sight, double vision, or a general malaise with general aches.

taken from here respectively

History of Brain Surgery

by John R. Mangiardi, M.D. and Howard Kane, Wm.

Brain surgery is perhaps the oldest of the practiced medical arts. No hard evidence exists suggesting a beginning to the practice of other facets of medicine such as pharmacology -- using drugs, chemical and natural ingredients to help a fellow human being. There is ample evidence, however, of brain surgery, dating back to the Neolithic (late Stone Age) period. Unearthed remains of successful brain operations, as well as surgical implements, were found in France-- at one of Europe's noted archeological digs.

And, the success rate was remarkable, even circa 7,000 B.C.

But, pre-historic evidence of brain surgery was not limited to Europe. Pre-Incan civilization used brain surgery as an extensive practice as early as 2,000 B.C. In Paracas, Peru, a desert strip south of Lima, archeologic evidence indicates that brain surgery was used extensively. Here, too, an inordinate success rate was noted as patients were restored to health. The treatment was used for mental illnesses, epilepsy, headaches, organic diseases, osteomylitis, as well as head injuries.

Brain surgery was also used for both spiritual and magical reasons; often, the practice was limited to kings, priests and the nobility.

Surgical tools in South America were made of both bronze and man-shaped obsidian (a hard, sharp-edged volcanic rock).

Africa showed evidence of brain surgery as early as 3,000 B.C. in papyrus writings found in Egypt. "Brain," the actual word itself, is used here for the first time in any language. Egyptian knowledge of anatomy may have been rudimentary, but the ancient civilization did contribute important notations on the nervous system.

Hippocrates, the father of modern medical ethics, left many texts on brain surgery. Born on the Aegean Island of Cos in 470 B.C., Hippocrates was quite familiar with the clinical signs of head injuries. He also described seizures accurately, as well as spasms and classified head contusions, fractures and depressions. Many concepts found in his texts were still in good stead two thousand years after his death in 360 B.C.

Ancient Rome in the first century A.D. had its brain surgeon star, Aulus Cornelius Celsus. Hippocrates did not operate on depressed skull fractures; Celsus often did. Celsus also described the symptoms of brain injury in great detail.

Asia was home to many talented brain surgeons: Galenus of Pergamon, born in Turkey, and the physicians of Byzance such as Oribasius (4th century) and Paul of Aegina. An Islamic school of brain surgery also flourished from 800 to 1200 A.D., the height of Islamic influence in the world. Abu Bekr Muhammed el Razi, who lived from 852 to 932 in the Common Era, was perhaps the greatest of Islamic brain srugeons. A second Islamic brain surgeon, Abu l'Qluasim Khalaf, lived and practiced in Cordoba, Spain, and was one of the great influences on western brain surgery.

The Christian surgeons of the Middle Ages were clerics, well educated, knowledgeable in Latin, and familiar with the realm of medical literature. Despite the church's ban on study of anatomy, many churchmen of great renown (advisors and confessors to a succession of Popes) were outstanding physicians and surgeons. Leonardo Davinci's portfolio containing hundreds of accurate anatomical sketches indicates the intense intellectual interest in the workings of the human body despite the Church's ban.