Biallelic Loss-of-Function Variants in Are Associated with Peripheral Neuropathy and Hearing Loss.

Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control.

Lack of effect on ambulation of dalfampridine-ER (4-AP) treatment in adult SMA patients.

SMA is a genetically determined motor system disorder that results in muscle weakness, selective motor neuron death, muscle atrophy, and impaired functional mobility. In SMA model systems, long-term treatment with 4-aminopyridine (4-AP) has been shown to improve motor function. To assess tolerability and preliminary efficacy of 4-AP on walking ability, endurance and EMG in adult ambulatory SMA patients, we conducted a double blind, placebo control, crossover pilot study with dalfampridine (4-AP, 10 mg BID).

Neuromuscular disorders in pregnancy.

Many neuromuscular disorders preexist or occur during pregnancy. In some cases, pregnancy unmasks a latent hereditary disorder. Most available information is based on case reports or series or retrospective clinical experience or patient surveys.

Peripheral neuropathy symptoms in wild type transthyretin amyloidosis.

To propose a correlation between polyneuropathy and ATTRwt based on retrospective analysis of patients with ATTRwt. We reviewed 151 ATTRwt patients followed by the amyloid cardiac clinic (group A) for symptoms of neuropathy and 12 patients with ATTRwt evaluated in the Neurology Department (group B) with objective measures of neuropathy. Medical history, electrodiagnosis, laboratory and skin biopsies were assessed; 30.

Update on Chemotherapy-Induced Peripheral Neuropathy.

Purpose Of Review: The purpose of this study was to briefly discuss chemotherapy-induced peripheral neuropathy (CIPN) and detail the most important and most recent chemotherapeutic agents implicated. This review will examine neuropathy mechanisms, risk factors, and clinical patterns; novel and prospective drugs with similar effects that are less well known to neurologists are discussed.

Recent Findings: CIPN is increasingly recognized for its clinical importance and effect on patient quality of life.

Syncope: Case Studies.

Syncope, or the sudden loss of consciousness, is a common presenting symptom for evaluation by neurologists. It is not a unique diagnosis but rather a common manifestation of disorders with diverse mechanisms. Loss of consciousness is typically preceded by a prodrome of symptoms and sometimes there is a clear trigger.

Bortezomib-associated demyelinating neuropathy--clinical and pathologic features.

Objectives: Bortezomib is a proteasome inhibitor that is frequently used for multiple myeloma and lymphoma. A sensory predominant axonal neuropathy is associated with bortezomib treatment but a demyelinating neuropathy is also described primarily based on electrodiagnostic findings. We report a series of patients treated with bortezomib who developed peripheral neuropathy and were found to have demyelinating features on electrodiagnostic testing.

Discordant phenotype in monozygotic female twins with Lys35Thr TTR familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy is the hereditary form of transthyretin amyloidosis that is rapidly progressive. Discordant expression of Val30Met transthyretin amyloid in monozygotic twins has been reported in the past, in Europe and Asia. We report the first case of discordant expression of Lys35Thr transthyretin amyloid in female monozygotic twins in North America with eye involvement and peripheral neuropathy.

Neurologic complications of alcoholism.

Purpose Of Review: This review serves as an overview of neurologic conditions associated with alcohol abuse or withdrawal, including epidemiology, clinical symptoms, diagnostic approach, and treatment.

Recent Findings: Frequent alcohol abuse and frank alcoholism are very common among adults in the United States. Although rates decline with each decade, as many as 10% of the elderly drink excessively.

Association between patient reported outcomes and quantitative sensory tests for measuring long-term neurotoxicity in breast cancer survivors treated with adjuvant paclitaxel chemotherapy.

Neurotoxicity is a common side-effect during taxane therapy. The prevalence and severity of long-term neurotoxicity following therapy is unknown. The authors conducted a cross-sectional study of 50 consecutive patients with stage I-III BC, who were within 6 months and 2 years of completing adjuvant taxane therapy and a prospective study of 50 women initiating taxane therapy.

Development of recurrent facial palsy during plasmapheresis in Guillain-Barré syndrome: a case report.

Introduction: Guillain-Barré syndrome is an immune-mediated polyneuropathy that is routinely initially treated with either intravenous immunoglobulin or plasmapheresis. To the best of our knowledge, no association between plasmapheresis treatment and acute onset of facial neuropathy has been reported.

Case Presentation: A 35-year-old Caucasian man with no significant prior medical history developed ascending motor weakness and laboratory findings consistent with a diagnosis of Guillain-Barré syndrome.

Autonomic testing: common techniques and clinical applications.

Laboratories able to test autonomic function are increasingly available and rely on batteries of well-accepted, noninvasive tests. Tests of parasympathetic cardiovagal, sympathetic vasoconstriction, and sudomotor (sweating) function are most commonly employed. Common examples include heart rate variability to various challenges, Valsalva maneuver, standing and tilt-table studies, and various sudomotor methods.

Neurological aspects of syncope and orthostatic intolerance.

Sudden falling with loss of consciousness from syncope and symptoms of orthostatic intolerance are common, dramatic clinical problems of diverse cause, but cerebral hypoperfusion is the ultimate mechanism in most. Cardiac, reflex, and orthostatic hypotension are important forms to consider. Syncope must be differentiated from seizures, psychiatric events, drop attacks, and other mimics.

Update on medication-induced peripheral neuropathy.

Despite improvements in the identification of causes of peripheral neuropathy, idiopathic polyneuropathy remains common. Medication and toxic neuropathy account for a small but important percentage of potentially preventable or reversible causes of neuropathy. New drugs that can induce neuropathy have been approved over the past several years, including the anticancer agents bortezomib, ixabepilone, and oxaliplatin.

The electrodiagnosis of neuropathy: basic principles and common pitfalls.

Electrodiagnostic studies are a critical tool for the identification and study of peripheral neuropathy, enabling definition of the pathophysiologic type of nerve injury, its distribution, severity, and the degree of motor or sensory nerve involvement. These data help to differentiate the varieties of neuropathy from other neuromuscular diseases. Nerve conduction studies and electromyography, although widely performed, are complex techniques and are subject to a wide range of artifacts, which can result in missed or erroneous diagnoses.

Multifocal motor neuropathy with conduction block: slow but not benign.

Objective: To describe a patient with multifocal motor neuropathy with conduction block who had annual clinical and physiological examinations for 18 years but declined treatment for personal reasons.

Design: Case report.

Setting: Collaboration between 2 academic tertiary care hospitals.

Immune-mediated autonomic neuropathies.

Improved recognition and availability of noninvasive testing of autonomic disorders has prompted a better understanding of disease mechanisms of some disease forms, especially potentially treatable immune-mediated autonomic neuropathies. Development is acute, subacute, or less commonly chronic. Autonomic involvement is common and an important cause of morbidity and mortality in Guillain-Barré syndrome.

Medication-induced exacerbation of neuropathy in Charcot Marie Tooth disease.

Toxin or medication-induced worsening of preexisting peripheral neuropathy is a generally accepted but not well-studied phenomenon in humans. Drug-induced exacerbation of Charcot Marie Tooth disease (CMT) neuropathy is a common concern; a list of potential drugs to avoid is maintained by the CMT Association but with limited direct evidence or advice on relative risk. An extensive literature search for reported cases of drug effects in CMT patients found the vast majority concerned excessive vincristine toxicity in patients with undiagnosed demyelinating forms of CMT, many after 1 or 2 doses.

Medication and toxin-induced peripheral neuropathy.

Medication and toxin-induced neuropathies, although uncommon, are important to identify because of potential reversibility. Numerous medications and toxins are implicated with neuropathy, but objective proof is lacking for many. Chemotherapeutic agents, nucleoside analogs, and other medications and toxins have clear causative links with neuropathy, but many agents have only rare temporal associations.

Rituximab treatment of an IgM monoclonal autonomic and sensory neuropathy.

Rituximab, a monoclonal antibody against B-cell membrane marker CD-20, is an effective treatment for immunoglobulin M (IgM) monoclonal anti-myelin-associated glycoprotein (MAG) neuropathies. We report a patient with an autonomic and painful sensory neuropathy associated with an IgM lambda monoclonal gammopathy, responsive to rituximab. Treatment resulted in a decline in total IgM and improvement in the patient's painful neuropathy and dysautonomia.

Gene expression profiling in chronic inflammatory demyelinating polyneuropathy.

Gene expression in archived frozen sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was compared to that in vasculitic nerve biopsies (VAS) and to normal nerve (NN) by DNA microarray technology. Hierarchical clustering analysis demonstrated distinct gene expression patterns distinguishing these disease groups. Of particular interest were: (1) Tachykinin precursor 1, which may be involved in pain mediation; (2) Stearoyl-CoA-desaturase, which may be a marker for remyelination and (3) the Allograft Inflammatory Factor 1 (AIF-1), a modulator of immune response during macrophage activation.

Comparison of electrodiagnostic abnormalities and criteria in a cohort of patients with chronic inflammatory demyelinating polyneuropathy.

Background: Current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) are research oriented favoring specificity over sensitivity. Application of such criteria in clinical practice may miss the diagnosis in potentially treatable patients.

Objectives: To analyze the electrophysiologic abnormalities in a cohort of patients with clinically defined CIDP, to compare these data with published electrodiagnostic criteria, and to identify a set of abnormalities that is shared by all patients with CIDP.