The National Registry of Veterans with amyotrophic lateral sclerosis.

BACKGROUND: The Department of Veterans Affairs (VA) Cooperative Studies Program has established a National Registry of Veterans with Amyotrophic Lateral Sclerosis (ALS). This article describes the objectives, methods, and sample involved in the registry. METHODS: United States military veterans with ALS were identified through national VA electronic medical record databases and nationwide publicity efforts for an enrollment period of 4 1/2 years. Diagnoses were confirmed by medical record reviews. Registrants were asked to participate in a DNA bank. Follow-up telephone interviews are conducted every 6 months to track participants' health status. RESULTS: As of September 30, 2007, 2,400 veterans had consented to participate in the registry, 2,068 were included after medical record review, 995 were still living and actively participating, and 1,573 consented to participate in the DNA bank. 979 participants had been enrolled in the registry for at least 1 year, 497 for at least 2 years, and 205 for at least 3 years. Fourteen studies have been approved to use registry data for epidemiological, observational, and interventional protocols. CONCLUSION: This registry has proven to be a successful model for identifying large numbers of patients with a relatively rare disease and enrolling them into multiple studies, including genetic protocols.

Apolipoprotein E and neuromuscular disease: a critical review of the literature.

Molecular mechanisms that alter the incidence and rate of neuromuscular disease progression are, in many cases, only partially understood. Several recent studies have asked whether apolipoprotein E (apoE for the protein, APOE for the gene) influences these aspects of specific neuromuscular disorders, as it does in central nervous system disorders such as Alzheimer disease. Although these studies are open to methodological criticism, several interesting trends have emerged. First, the APOE4 allele seems to be associated with an increased risk for developing certain neuromuscular diseases, including diabetic neuropathy and human immunodeficiency viral neuropathy. Second, this allele appears to be associated with faster progression of some neuromuscular diseases, including diabetic neuropathy and possibly motor neuron disease. Third, the APOE2 allele seems to confer protection against developing certain neuromuscular diseases, including the amyotrophic lateral sclerosis (ALS)/parkinsonism/dementia complex of Guam. Finally, this allele is associated with a better prognosis in neuromuscular diseases such as motor neuron disease. The effect of various APOE alleles on neuromuscular diseases therefore parallels their influence on central nervous system diseases. Arch Neurol. 2000;57:1561-1565

Surgical treatment of carpal tunnel syndrome in patients with peripheral neuropathy.

Outcome after carpal tunnel surgery was studied retrospectively in 32 patients with peripheral neuropathy and carpal tunnel syndrome. Nocturnal paresthesias were almost universally relieved, followed in order of responsiveness by pain, numbness, and weakness. Twenty-five of 28 patients said they would have the surgery again if the outcome were the same. Patients with carpal tunnel syndrome and peripheral neuropathy benefit from surgical treatment of carpal tunnel syndrome.

Use of specialized coagulation testing in the evaluation of patients with acute ischemic stroke.

OBJECTIVE: To investigate the use and appropriateness of specialized coagulation tests in the evaluation of patients with acute ischemic stroke and identify factors that influence test ordering. BACKGROUND: Coagulation abnormalities are a rare but recognized cause of ischemic stroke. METHODS: Patient demographics, stroke risk factors, history of venous thrombosis or miscarriage, family history of stroke, and the results of specialized tests for coagulation disorders were recorded for a consecutive series of ischemic stroke patients over age 18 admitted to an academic medical center over 3 years (n = 674). Factors associated with testing were identified with univariate analyses in a random sample of two-thirds of the patients (n = 450). Multivariate logistic regression modeling was then used to identify variables independently associated with testing and then validated in the remaining patients (n = 224). RESULTS: Of the 31% of patients (n = 208) tested for coagulopathies, 29% (n = 60) were tested when the result was unlikely to influence therapeutic decisions. Historical factors associated with an increased incidence of a coagulopathy, such as history of venous thrombosis or miscarriage, were not commonly documented. The absence of small-artery atherosclerosis (OR 0.36, 95% CI 0.17 to 0.76) and younger age (OR 0.89 per year, 95% CI 0.87 to 0.92) were independently related to the frequency of specialized coagulation testing. CONCLUSIONS: One-third of specialized coagulation tests were ordered when the test results were unlikely to affect therapeutic decisions. Age was the only clinical factor increasing the likelihood of a coagulopathy that appeared to influence ordering of specialized coagulation tests.

Neuro-Behçet's disease: factors hampering proper diagnosis.

We reviewed the clinical course of nine patients with neuro-Behçet's disease to assess difficulties in making this diagnosis. Factors delaying proper diagnosis included lack of accurate history and physical examination, lack of recognition of an underlying systemic syndrome and its relationship to the neurologic symptoms, presence of intermittently normal CSF studies, and use of noncontrasted neuroimaging techniques.

Electron microscopic diagnosis of human flavivirus encephalitis: use of confocal microscopy as an aid.

The distinction between intracranial viral infections and inflammatory conditions requiring immunosuppression is important. Although specific laboratory reagents are readily available for some viruses, diagnosis of arbovirus infection is more difficult. Transmission electron microscopy (TEM) theoretically allows identification of viral particles independent of reagent availability, but it has limited sensitivity. We report two cases of human flavivirus encephalitis diagnosed by TEM. Laser scanning confocal microscopy (LSCM) was used in one case to survey unembedded tissue slices for focal abnormalities, from which fragments smaller than 1 mm2 were excised for epoxy embedding. This facilitated TEM identification of intracytoplasmic, budding, 35-40 nm spherical virus particles, confirmed by serology as St. Louis encephalitis. In contrast to mosquitoes and newborn mice, in which high viral loads are associated with minimal tissue responses, these biopsies showed florid angiodestructive inflammation and microgliosis, with rare virions in necrotic perivascular cells and astrocytes. To our knowledge, this represents the first ultrastructural study of St. Louis encephalitis in humans, indicating the potential value of LSCM-aided TEM.

Cyclosporin A-related cerebral vasculopathy.

The use of cyclosporin A has been associated with several side-effects, including neurotoxicity. The mechanism of toxicity is not well known. We report two patients treated with cyclosporin A who developed lesions in the cerebral white matter associated with abnormally elevated cerebral blood flow velocities on transcranial doppler ultrasound and abnormal vascular appearance on magnetic resonance angiography. Bone Marrow Transplantation (2000) 26, 801-804.

Aspergillus disc space infection: case report and review of the literature.

Aspergillus disc space infection is an unusual complication of the immunocompromised state. Magnetic resonance imaging may aid the clinician in arriving at a prompt diagnosis of discitis in affected patients. We report a case of systemically acquired Aspergillus discitis at multiple levels diagnosed by plain x-ray films, bone scan, magnetic resonance imaging, and biopsy. We review the literature on this subject and suggest that aggressive diagnosis with early biopsy, treatment with systemic antifungal agents, and surgical debridement of the infected disc space yield the best outcome for these patients.

Surgical treatment of cluster headache.

Cluster headache is ordinarily managed medically, but may become refractory to such medical management. In this setting, surgical treatment has occasionally been performed, based on evidence that pertinent pain pathways and parasympathetic pathways may be interrupted at the main sensory root of the trigeminal nerve and at the nervus intermedius. Between 1976 and 1987, 13 patients underwent surgery for treatment of cluster headache that was refractory to medical therapy (15 procedures). Partial sectioning of the main sensory root and sectioning of the nervus intermedius were performed in nine patients; only partial sectioning of the main sensory root in one; only sectioning of the nervus intermedius in one; and nervus intermedius sectioning plus microvascular decompression of the trigeminal nerve in two. The average postoperative period for the 13 patients was 37 months (range 2 to 135 months). All patients had return of their headaches postoperatively except for one patient who obtained relief after a repeat procedure. Headache began to return between 2 days and 2 years postoperatively. Three patients are currently free of headache, including both patients who had nervus intermedius sectioning plus microvascular decompression of the trigeminal nerve. Together with recurrence of headache, cluster-associated autonomic disturbances recurred after 14 of the 15 operations but are currently absent in the three headache-free patients. Partial sectioning of the main sensory root and sectioning of the nervus intermedius, as performed in these patients, seem to have limited value in the treatment of cluster headache.

EKG abnormalities in pediatric patients with myotonic dystrophy.

Electrocardiographic (EKG) abnormalities are frequent in patients with myotonic dystrophy; cardiac complications may lead to significant morbidity and mortality. The charts of 17 pediatric patients with myotonic dystrophy were reviewed to ascertain the frequency of EKG abnormalities and cardiovascular symptoms. Fifteen of 17 patients had abnormal EKGs with sinus bradycardia being the most common abnormality. Only 1 of 17 patients had cardiovascular symptoms. Four patients had moderate to severe weakness and 3 of them had a conduction disturbance (i.e., first-degree AV block or intraventricular conduction delay). Two of the remaining 13 patients with mild weakness had conduction disturbances. No pediatric patients had progressive EKG abnormalities during follow-up. Baseline EKG study of pediatric patients with myotonic dystrophy is recommended because abnormalities are frequent and usually asymptomatic. Frequent follow-up EKGs are probably unnecessary unless the patient is symptomatic or has heart block.

Recognizing peripheral neuropathy. How to read the clues to an underlying cause.

Several systemic diseases, including some common ones (eg, diabetes, rheumatoid arthritis, thyroid disease) can cause symptoms of peripheral nerve dysfunction. Efficient identification and treatment of the underlying disorder can avoid costly and unnecessary testing. Patients' descriptions of symptoms and their onset, specific deficits found on physical examination, and family and medical history provide many clues to the cause of the neuropathy. Nerve-conduction studies, electromyography and, when necessary, nerve biopsy serve as complements to clinical evaluation.

Lumbar puncture and CSF examination. Answers to three commonly asked questions.

The incidence of post-lumbar puncture headache has been shown to be reduced by using a higher-gauge (smaller-bore) needle and orienting the needle bevel parallel to the dural fibers. Incidence of headache is the same in patients given bed rest as in patients who are mobilized immediately. Cerebrospinal fluid (CSF) examination of patients with seizures of unclear cause is indicated. However, pleocytosis can be a result of the seizure alone. Other causes of pleocytosis must be ruled out by clinical evaluation and CSF studies. Although lumbar puncture is often advocated for patients presenting with dementia, it usually is not helpful in finding a specific cause if the dementia is long-standing.

Peripheral neuropathy in patients with chronic renal failure. A treatable source of discomfort and disability.

Uremic polyneuropathy occurs in about half of patients undergoing dialysis and is characterized by axonal degeneration with secondary segmental demyelination. Hemodialysis or peritoneal dialysis halts the progress of polyneuropathy but usually does not bring improvement. However, improvement invariably occurs with successful renal transplantation. Mononeuropathies resulting from placement of forearm arteriovenous fistulas are also seen and include the commonly encountered carpal tunnel syndrome and the rare but catastrophic ischemic monomelic neuropathy. The latter constitutes a medical emergency; immediate surgical closure of the fistula is required to avoid severe and permanent neurologic dysfunction.

Endocrinologic causes of peripheral neuropathy. Pins and needles in a stocking-and-glove pattern and other symptoms.

In the Western world, diabetes is the biggest cause of peripheral neuropathy, usually distal symmetric polyneuropathy but some times another polyneuropathy or a focal neuropathy. In addition, hypothyroidism and acromegaly can cause carpal tunnel syndrome and other sensory complaints. A complete blood cell count, nerve-conduction tests, thyroid-function tests (needed in all patients with carpal tunnel syndrome), and when necessary, needle electromyography can help confirm the diagnosis. Treatment of underlying disease is the most successful management approach: Tight glucose control in diabetic patients, thyroid hormone replacement therapy in patients with hypothyroidism, and removal of the pituitary adenoma in patients with acromegaly are of proven benefit. Significant symptomatic relief of dysesthesias can be obtained with use of capsaicin cream, tricyclic antidepresants, anticonvulsant agents, or an antiarrhythmic drug.

Peripheral neuropathy and connective tissue disease. Watch for this twosome when hunting for a diagnosis.

Coexistent peripheral neuropathy and connective tissue disease is fairly common, possibly because immune-mediated factors are often present in both disorders. Awareness of the association between the two conditions can be important during diagnostic evaluation, because neuropathy is sometimes the presenting feature of previously unrecognized connective tissue disease. In this article, the authors examine clinical findings in vasculitic, nonvasculitic, and treatment-related neuropathy, concentrating on the essentials of diagnosis and treatment.

Initial evaluation of suspected dementia. Asking the right questions.

The initial clinical approach to suspected dementia involves asking the right questions of the patient and a knowledgeable family member or caregiver. These questions should focus on the nature of the cognitive problem (e.g., the onset, duration, and severity of memory difficulties). The clinical interview is supplemented with thorough examination of the patient's physical, neurologic, mental, and functional status. Once a diagnosis of dementia is established, the underlying cause should be identified by a standardized workup, including laboratory testing and, in most cases, neuroimaging. Genetic testing for the APOE epsilon 4 allele can help confirm the diagnosis in patients with late-onset familial or sporadic Alzheimer's disease.

Update on Alzheimer's disease. Promising advances in detection and treatment.

In the past decade, significant progress has been made in the understanding and treatment of Alzheimer's disease. Modest success has been achieved using new drugs in treatment of mild symptoms of the disease. Vitamin E, estrogen, and NSAIDs may slow the progression of Alzheimer's disease, but their routine use is not without risk, and there is no evidence that these agents are effective in preventing the disease in asymptomatic people. With our increased understanding of the pathogenesis of Alzheimer's disease, it is likely that the next decade will see further refinement and development of treatment strategies to halt progression and possibly reduce the incidence of disease.

Managing common behavioral problems in dementia. How to improve quality of life for patients and families.

Dementia is the most common reason for nursing home placement, and related behavioral symptoms are the primary factors precipitating the decision. Disruptive behaviors such as depression, sleep disturbance, agitation, aggression, and psychosis can tax family members' abilities to care for a loved one who has reached that stage of the illness. Working with families to institute effective management strategies may help delay institutionalization. In this article, Drs Burke and Morgenlander present a systematic approach to identifying and treating common problems in dementia.

Bell's palsy. Ensuring the best possible outcome.

Bell's palsy is thought to be an idiopathic polyneuritis and must be distinguished from other disorders that cause facial weakness. In most cases, differentiation can be accomplished on the basis of the history, physical examination, and clinical course. Routine follow-up care ensures that recovery is occurring. Electrodiagnostic testing often helps to assess prognosis. Eye care and corticosteroid therapy are recommended.

Determining the cause of memory loss in the elderly. From in-office screening to neuropsychological referral.

Improved understanding of neurobehavior in normal aging, Alzheimer's disease, and late-life depression makes early detection of neurodegenerative conditions possible. Primary care physicians can screen patients' mental status and mood states with simple in-office tests. When screening results or the clinical picture is ambiguous or complex, neuropsychological evaluation is useful in making an early, reliable differentiation between dementia and normal aging. Early identification of neurologic problems provides an opportunity to enhance quality of life and long-term care. Medical interventions, such as a trial of donepezil hydrochloride (Aricept) or other memory-enhancing medications as they become available, can be started when results are likely to be optimal. Common coexisting problems (e.g., depression, falls) can be sought and managed. Additional important medical decisions (e.g., elective surgeries) may be considered differently when dementia is diagnosed early.