Neurosarcoidosis: clinical features, diagnosis, and management.

Sarcoidosis is a multisystemic granulomatous disease, which uncommonly affects nervous system. However, when present, it may affect both central and peripheral nervous systems and potentially mimics other chronic diseases of the nervous system. Pathogenesis of neurosarcoidosis remains largely unknown, and its diagnosis and management pose serious challenges to clinicians. Early diagnosis and aggressive treatment of neurosarcoidosis are necessary to produce satisfactory clinical outcomes. This review discusses clinical manifestations, current diagnostic studies, and currently available modalities for management of neurosarcoidosis.

Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of combination therapy with intramuscular interferon beta-1a and oral doxycycline, a potent inhibitor of matrix metalloproteinases, in patients with relapsing-remitting multiple sclerosis (RRMS) having breakthrough disease activity. DESIGN: Open-label, 7-month trial. SETTING: Louisiana State University Health Sciences Center, Shreveport. PATIENTS: Fifteen patients with RRMS taking interferon beta-1a with breakthrough disease activity took doxycycline for 4 months. Patients underwent monthly neurologic examination, magnetic resonance imaging of the brain using triple-dose gadolinium, and safety blood work. INTERVENTIONS: Ongoing treatment with intramuscular interferon beta-1a plus oral doxycycline, 100 mg daily, for 4 months. MAIN OUTCOME MEASURES: The primary end point was gadolinium-enhancing lesion number change, and the secondary end points were relapse rates, safety and tolerability of the combination of interferon beta-1a and doxycycline in patients with MS, Expanded Disability Status Scale score, serum matrix metalloproteinase-9 levels, and transendothelial migration of monocytes exposed to serum from patients with RRMS. RESULTS: Combination of doxycycline and interferon beta-1a treatment resulted in reductions in contrast-enhancing lesion numbers and posttreatment Expanded Disability Status Scale values (P < .001 for both). Only 1 patient relapsed. Multivariate analyses indicated correlations between decreased serum matrix metalloproteinase-9 levels and enhancing lesion activity reduction. Transendothelial migration of monocytes incubated with serum from patients with RRMS undergoing combination therapy was suppressed. Adverse effects were mild; no adverse synergistic effects of combination therapy or unexpected adverse events were reported. CONCLUSIONS: Combination of intramuscular interferon beta-1a and oral doxycycline treatment was effective, safe, and well tolerated. Controlled clinical trials in larger cohorts of patients with MS are needed to evaluate the efficacy and tolerability of this combination. Trial Registration clinicaltrials.gov Identifier: NCT00246324

Metabolic and Toxic Myelopathies.

PURPOSE OF REVIEW: Myelopathy may occur as a consequence of various metabolic and toxic conditions. This article provides an update on the clinical presentations, diagnostic evaluations, and management of metabolic and toxic myelopathies. RECENT FINDINGS: Myelopathy and myeloneuropathy due to vitamin B12 deficiency is increasing in prevalence partly because of an aging population. Early recognition of the clinical symptoms and rapid initiation of treatment is essential. Copper deficiency is now also recognized as causing a similar clinical picture as vitamin B12 deficiency. Conditions leading to copper deficiency include bariatric surgery and excessive zinc intake. Unusual conditions such as lathyrism and konzo are relevant to all neurologists because of emigration from less well-developed countries. Myelopathy can also occur from substance abuse (eg, heroin and nitrous oxide), and early diagnosis could lead to improved patient outcomes. The spinal cord may also be injured in decompression illness that occurs in sport divers and individuals who work in pressurized atmospheres. SUMMARY: Knowledge and recognition of the various metabolic and toxic causes of myelopathy is important for the practicing neurologist, as timely diagnosis and rapid initiation of therapy is essential to improve the chances for recovery.

Liver Disease and Neurology.

PURPOSE OF REVIEW: Neurologists often encounter patients with acute and chronic liver disease and must be aware of how these diseases can affect the nervous system. This is particularly true when evaluating patients with alterations in cognition and level of consciousness. Wilson disease, while uncommon, is a treatable condition with many neurologic and psychiatric symptoms. Neurologic disorders associated with liver disease may affect not only the brain, but also the spinal cord and peripheral nervous system. This article reviews the association of liver disease and the nervous system and provides new information regarding diagnostic and therapeutic approaches to evaluating patients with liver diseases. RECENT FINDINGS: Early recognition of hepatic encephalopathy may be possible using a combination of clinical suspicion and various neuropsychological studies. Management of severe hepatic encephalopathy from acute liver failure is important to neurologists involved in neurocritical care. Next-generation genetic testing may aid in the diagnosis of patients suspected of having Wilson disease. The relationship of numerous neurologic findings from hepatocerebral degeneration and from viral hepatitis is more widely recognized. SUMMARY: It is important for neurologists to recognize the neurologic symptoms that may occur in patients with acute and chronic liver failure, Wilson disease, and viral hepatitis to inform prompt diagnostic and management decisions.

Treatment of symptoms in multiple sclerosis.

The current focus regarding treatment of multiple sclerosis (MS) to be on therapies that may alter the course of the disease. Some of the evidence regarding the efficacy of these treatments is based on changes in the appearance of neuroimaging studies of the brain and spinal cord and not on the effect of these treatments on clinical symptomatology. Since most of our patients with MS continue to be symptomatic despite the use of immunomodulating agents, it is important for the treating neurologist to be familiar with treatments for these symptoms, many of which are extremely disabling to the patient. Knowing how to deal with common complaints/symptoms of MS enables us to better practice the art of neurological care.

Metabolic, nutritional, and toxic myelopathies.

This review article identifies and describes the clinical manifestations of various metabolic, nutritional, and toxic conditions that result in symptoms of myelopathy and, in some cases, myeloneuropathy. It includes discussions of the clinical pictures that occur secondary to these causes. Familiarity with the clinical symptoms may lead to accurate diagnosis through laboratory and imaging studies and to treatment with successful identification of the underlying causes.

Neurologic presentations of hepatic disease.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that develops in the context of portosystemic venous shunting, in the presence or absence of intrinsic hepatic disease. HE is clinically characterized by altered sensorium and a spectrum of neuropsychiatric abnormalities. Several hypotheses have been proposed to explain the underlying pathogenic mechanisms of altered brain function associated with advanced hepatic disease and portosystemic shunting. HE may lead to profound coma and death; however, in many cases it is reversible. This article discusses the most recent developments in understanding the pathophysiology of HE and its diagnosis and management.

Brachial neuritis with bilateral diaphragmatic paralysis following herpes zoster: a case report.

We present a case of supine respiratory failure due to a bilateral diaphragmatic paralysis associated with brachial neuritis secondary to thoracic herpes zoster. Fluoroscopy in both the standing and supine positions revealed bilateral diaphragmatic paralysis accentuated in the supine position. To our knowledge, this is the first case of thoracic herpes zoster associated with brachial neuritis and bilateral diaphragmatic paralysis.

Painful brachial plexopathies in SEPT9 mutations: adverse outcome related to comorbid states.

Hereditary neuralgic amyotrophy (HNA), an autosomal dominant disorder associated with SEPT9 mutation located on chromosome 17q25, causes recurrent painful weakness with sensory disturbances in a brachial distribution. We present electrophysiological, clinical phenotype, and molecular genetic data of three members from a family with HNA with the C262T SEPT9 mutation. The degree of motor weakness and recovery is variable within this family. Severity and recovery from motor deficits may have been a function of comorbid medical conditions. To our knowledge, this is the first report to confirm SEPT9 mutation in a family with suspected HNA.

Gender issues in multiple sclerosis.

Multiple sclerosis (MS) varies considerably in the way that it affects females and males. The prevalence of the disease is much greater in women and tends to follow a different clinical course than it follows in the affected male population. It is also well known that MS symptoms often are much less of a problem during pregnancy. This chapter discusses possible explanations for gender differences based on sex hormones as well as the effects of these hormones on cytokines and other factors that may influence the course of MS. Knowledge of these effects may hold some promise in other types of treatment for MS. Since MS is much more prevalent in women of child-bearing age, there are also implications for the use of disease-modifying agents as well as drugs and treatments that may be useful for treatment of MS. MS often causes symptoms of sexual dysfunction, but there may be effective treatment for many of these treatments.

Evolving therapies for multiple sclerosis.

The introduction of immunomodulatory and immunosuppressive agents for treatment of multiple sclerosis (MS) has forever altered the natural course of this incurable and disabling neurodegenerative disorder. Despite early diagnosis of relapsing-remitting MS and early initiation of therapy, patients still experience breakthrough relapses and progression of their underlying MS pathology. The imperfect effectiveness, side effects, and toxicity of these agents, emphasize the necessity for development of more effective medications with less adverse events. This chapter presents readers with the most current information on the nature, mechanism(s) of action, and side effects of the most promising experimental agents currently under clinical trials. Some of the agents now at different stages of clinical trial have emerged as both safe and promising. The understanding of MS etiology will lead to the development of increasingly specific, safer, and effective treatments for MS by neuroscientists and neurologists.

Management of myasthenia gravis.

Myasthenia gravis (MS) is an immune-mediated disorder characterized by fluctuating weakness and fatigue of voluntary muscles. The muscular disorder is generalized in 85% and confined to extraocular muscles in 15% of patients. Pathophysiology of MG involves generation of antiacetylcholine receptor antibodies, which leads to a reduction of the number of acetylcholine receptors at the muscular motor endplate. This in turn results in fewer acetylcholine receptors available for stimulation, lower amplitude stimulations, less muscle fiber activation, and the eventual development of weakness in the affected muscles. The diagnostic workup for MS consists of administration of anticholinesterase agents (Tensilon test), repetitive nerve stimulation, Ach-R antibody assay, and single-fiber electromyography. Management of patients with MG includes cholinesterase inhibitors, corticosteroids, thymectomy, immunosuppressants, plasma exchange, and IVIg.