Validation of the triple timed up-and-go test in Lambert-Eaton myasthenia.

Introduction: There are no validated, practical, and quantitative measures of disease severity in Lambert-Eaton myasthenia (LEM).

Methods: Data from the Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome (DAPPER) trial were analyzed to assess triple timed up-and-go (3TUG) reproducibility and relationships between 3TUG times and other measures of LEM severity.

Results: The coverage probability technique showed ≥0.

Novel valosin-containing protein mutations associated with multisystem proteinopathy.

Over fifty missense mutations in the gene coding for valosin-containing protein (VCP) are associated with a unique autosomal dominant adult-onset progressive disease associated with combinations of proximo-distal inclusion body myopathy (IBM), Paget's disease of bone (PDB), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). We report the clinical, histological, and molecular findings in four new patients/families carrying novel VCP mutations: c.474 G > A (p.

3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia.

Introduction: 3,4-diaminopyridine has been used to treat Lambert-Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy.

Methods: We conducted a randomized double-blind placebo-controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in triple timed up-and-go (3TUG) times during tapered drug withdrawal.

Amyotrophic lateral sclerosis with positive anti-acetylcholine receptor antibodies. Case report and review of the literature.

Myasthenia gravis is a nerve-muscle junction disease, for which the most specific test is an increase in the anti-acetylcholine receptor antibodies (anti-AChR-Abs) titer. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting both upper and lower motor neurons. Positive AChR-Ab in patients with pure ALS are exceedingly rare.

Cognition, behavior, and respiratory function in amyotrophic lateral sclerosis.

Objective. To examine the relationship between respiratory functioning and neuropsychological performance, mood, and frontal-lobe-mediated behaviors in ALS patients. Methods.

Comparison of sudomotor and sensory nerve testing in painful sensory neuropathies.

Objective: To compare results of quantitative sudomotor axon reflex testing (QSART), dorsal sural, and sural sensory nerve testing in patients with painful sensory neuropathy (PSN).

Methods: Fifty-six patients with symptoms and neurologic examinations consistent with PSN who had both autonomic and nerve conduction studies were identified from 376 patients with a clinical diagnosis of painful neuropathy. Cases were clinically categorized as large-fiber or small-fiber neuropathies by described criteria.

Peripheral Nerve Society Guideline on processing and evaluation of nerve biopsies.

Nerve biopsy is often the final step in the diagnostic work-up of neuropathies of unknown origin. The aim of this guideline was to prepare an evidence-based guideline on the methods for performing and evaluating nerve biopsy. The panel performed a search of MEDLINE, hand search of bibliographies of the references retrieved, review of the evidence, and reached agreement by consensus.

A decrease in body mass index is associated with faster progression of motor symptoms and shorter survival in ALS.

Our objective was to test the hypothesis that changes in body mass index (BMI) are associated with changes in the clinical course of ALS. We examined the relationships between BMI at first clinical visit and changes in BMI up to a two-year follow-up, and multiple clinical variables related to ALS: age of onset, rate of progression of motor symptoms, and survival. Baseline BMI was classified according to the World Health Organization (WHO) criteria.

Frontal and temporal lobe involvement on verbal fluency measures in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) has been associated with changes in frontal and temporal lobe-mediated cognitive and behavioral functions. Verbal fluency, a sensitive measure to these changes, was utilized to investigate phonemic and semantic abilities in 49 ALS patients and 25 healthy controls (HCs). A subset of the ALS patients was classified as ALS-intact, ALS with mild cognitive impairments (ALS-mild), and ALS with fronto-temporal dementia (ALS-FTD) based on a comprehensive neuropsychological evaluation.

Mutilating acral ulcers: the spectrum of differential diagnosis.

Prominent acral mutilating ulcers can be present in sensorimotor neuropathies. Although diabetes mellitus is the most common cause of neuropathic ulcers, these skin lesions may manifest in nondiabetic neuropathies. The dermatologic abnormalities may even precede the onset of typical neuropathic symptoms, leading to diagnostic confusion.

The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors.

VAP proteins (human VAPB/ALS8, Drosophila VAP33, and C. elegans VPR-1) are homologous proteins with an amino-terminal major sperm protein (MSP) domain and a transmembrane domain. The MSP domain is named for its similarity to the C.

Diabetic neuropathies: unanswered questions.

Diabetic neuropathies are the most common types of neuropathies worldwide. Although there has been significant progress in the understanding of the clinical aspects of these conditions, many questions remain unanswered or difficult to answer in terms of causation, risk factors and genetic susceptibility, effective treatments and restoration of nerve functions, and pain management. The major handicap in studying diabetic neuropathies is the lack of a suitable animal model that addresses acute and chronic events leasing to diabetic neuropathy.

Myeloneuropathic presentation of spinal epidural lipomatosis.

Spinal epidural lipomatosis (SEL) is accumulation of unencapsulated fat tissue within the epidural space of the spinal canal. The most common cause of SEL is corticosteroid therapy, whereas most of the non-corticosteroid-dependent cases are idiopathic. If unrecognized, it may result in diagnostic confusion with other neuropathic or myelopathic conditions.

West Nile virus infection after cardiac transplantation.

West Nile virus is a mosquito-borne RNA Flavivirus infection transmitted to humans and other vertebrates, mainly by the Culex species of mosquito. Since the mid-1990s, the frequency and apparent clinical severity of West Nile virus outbreaks have increased. We report the case of a patient who developed West Nile virus encephalitis shortly after undergoing cardiac transplantation.

Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes.

Objective: Since the discovery of mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) ten years ago, testing for SOD1 gene mutations has become a part of the investigation of patients with suspected motor neuron disease. We searched for novel SOD1 mutations and for clinical characteristics of patients with these mutations.

Methods: Analysis was made of patient files at the Neurogenetic DNA Diagnostic Laboratory at Massachusetts General Hospital.

Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma.

Background: The mendelian forms of progressive external ophthalmoplegia (PEO) associated with multiple mitochondrial DNA deletions are clinically heterogeneous disorders transmitted as dominant or recessive traits. Autosomal dominant PEO is caused by mutations in at least 3 genes: adenine nucleotide translocator-1 (ANT1), encoding the muscle-specific adenine nucleotide translocator; chromosome 10 open reading frame 2 (C10orf2), encoding Twinkle helicase; and polymerase gamma (POLG), encoding the alpha subunit of polymerase gamma. Mutations in POLG can also cause autosomal recessive PEO, which is often associated with multisystemic disorders.