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Neuroscience (SNI) Blog

'Brain Waves' Neuroscience (SNI) posts

Gamma Knife Radiosurgery for Treatment of Essential Tremor

Essential tremor (ET) is the most common type of movement disorder, affecting approximate­ly four out of 1000 people, and is significantly more common, though less recognized, than Parkinson’s disease. ET affects men and women equally and is inherited as an autosomal-dominant condition in about 60 percent of cases.

Although often referred to as benign essen­tial tremor, it is hardly benign in patients who may not be able to write legibly, hold a glass of water or use a knife and fork. ET is primarily an action tremor of the upper extremities but may involve resting tremor of the head and neck and/or lower jaw, and also tremor of the voice. The latter may be so severe that speech becomes unintelligible.

Medication and surgical treatment options

Primidone and beta blockers are useful in re­ducing tremor in the early stages of ET, but as the tremor progresses, medical management often becomes less effective or side effects can prevent the use of adequate doses of medication. ET pa­tients then are candidates for surgical or radiosur­gical treatment.

The mainstay of the surgical treatment of ET is deep brain stimulation (DBS), in which an electrode is implanted in the ventral inter­mediate nucleus (VIM) of the thalamus. Neurosurgeons Peter Nora, M.D., and Ryder Gwinn, M.D., have been implant­ing DBS electrodes at Swedish Medical Center for several years. The treatment is effective, but it requires implantation of permanent hardware (wires and batteries) into the brain and chest wall. Patients who take anticoagulants or have severe cardio­vascular disease are not suitable candidates for DBS. These patients, however, may be candidates for radiosurgical treatment.

A new option for difficult-to-treat patients

The Odd Syndrome of Bilateral 8th Nerve Tumors

Bilateral 8th cranial nerve tumors, also known as vestibular schwannomas or acoustic neuromas (see figure), are pathognomonic of a fascinating syndrome called central neurofibromatosis or neurofibromatosis type 2 (NF-2). NF-2 is a rare, autosomal-dominant disease with an incidence of 1 in 30,000 live births. The mechanism by which the genetic changes underlying NF-2 produce these tumors of a cranial nerve remains a mystery. Interestingly, two other associations are also sufficient to make a diagnosis of NF-2. These are unilateral VS at early age (< 30 years) plus two other specific lesions (meningioma, schwannoma other than VS, glioma or pre-senile cataract), and unilateral VS at early age with an affected first-degree parent, sibling or child. Patients with NF-2 usually present between the ages of 18 and 24 years with tinnitus, hearing loss and balance difficulties. Symptoms of unilateral tinnitus, asymmetric hearing loss or unresolving vertigo or imbalance warrant a gadolinium-enhanced MRI with a neurotological consultation to rule out brainstem pathology.

NF-2 is caused by inactivation of the NF-2 tumor suppressor gene on chromosome 22 (22q12.2) which encodes the "Merlin" protein. Like a double negative, inactivation of a tumor suppressor gene produces an autosomal-dominant inheritance pattern identical to classical activating mutations.

When a diagnosis of NF-2 is entertained, evaluation should include a complete family history; a detailed head and neck and neurological examination with attention to cranial nerve deficits, and an MRI of the brain with dedicated images to detect bilateral VS, meningiomas and optic gliomas. Spinal MRI with gadolinium should be performed to look for spinal meningiomas or schwannomas, and ophthalmologic evaluation should be obtained in cases with visual loss or with suspicion of juvenile cataracts.

Unilateral VS and NF-2

Defining Tertiary Care for Neurological Diseases

Health care for patients with neurological diseases in the United States occurs across mul­tiple levels, ranging from primary to tertiary care and, less common­ly, quaternary care.

The World Health Organization has defined primary care as the point where first medical contact occurs, and where coordination and continu­ity of medical services is managed. Primary care focuses on a broad range of ser­vices, rather than the diagnosis and treatment of diseases of a specific organ system, and thus primary-care providers (PCPs) have varying levels of comfort in the treatment of neurologi­cal disorders.

Secondary care is provided by specialists, such as general neurologists, who focus on dis­eases affecting a specific organ system, usually upon referral by a PCP. Both primary care and secondary care are provided in an outpatient setting or a general hospital setting.

Tertiary neurological care is provid­ed by subspecialists who treat a subset of conditions that affect the nervous system. Examples include:

Unfundable: Clinical trials for rare diseases and orphan drugs

The study of acetazolamide for idiopathic intracranial hypertension described on page 9 of the Spring issue of BrainWaves raises an important question about a neglected aspect of clinical trials: How do investigators obtain funding to study the efficacy of a drug that has no commercial potential?

Only 300 of the approximately 7,000 known human diseases are of interest to the biopharmaceutical industry from the standpoint of prevalence or commercial potential, according to the Office of Rare Diseases Research (ORDR) at the National Institutes of Health (NIH). The Orphan Drug Act of 1983 sought to use patent protection and tax incentives to promote development of drugs for diseases with a small market. In this context, the word “orphan” refers to a condition or drug that has not been “adopted” by the pharmaceutical industry because of limited commercial potential and a rare disease is one that affects 200,000 or fewer Americans. In the twenty years following enactment of the ODA, 249 orphan drugs received marketing authoriza¬tion, compared to 10 in the preceding decade, with the most notable being Amgen’s erythropoietin.

Commercial potential alone does not determine value

Low prevalence does not equate to limited commercial potential, of course, because pricing must also be considered.

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