use-capillary-electrophoresis-immunoassay-to-search-for-potential

Use of Capillary Electrophoresis Immunoassay to Search for Potential Biomarkers of Amyotrophic Lateral Sclerosis in Human Platelets

Capillary electrophoresis immunoassay (CEI), also known as capillary western technology, is becoming a method of choice for screening disease relevant ...

University of Kansas Medical Center

We report a 28-year-old man who presented with intestinal pseudo-obstruction as the initial manifestation of thymoma, myasthenia gravis, and dysautonomia. The patient's autoantibody profile was characteristic of this constellation of disorders, being positive for both muscle and ganglionic nicotinic acetylcholine receptor antibodies and striational antibody. Inflammatory cell infiltrates were found in the myenteric plexus of the stomach and small intestine. Review of 12 previously reported cases suggests that patients with both myasthenia gravis and dysautonomia in the context of thymoma respond poorly to therapy.

Myasthenia gravis, thymoma, and intestinal pseudo-obstruction: a case report and review.

We performed a retrospective chart review on 53 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients at nine university-based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9-79 years. Twenty-seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long-term (> or =3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG-related death. This survey reinforces several cardinal features of MuSK-Ab-positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long-term outcome is favorable in about 60% of cases.

Clinical findings in MuSK-antibody positive myasthenia gravis: a U.S. experience.

The primary aims of our study were to compare pregabalin and duloxetine in a neuromuscular clinic for diabetic neuropathic pain (DPN) and to study the effect of these medications in cryptogenic sensory polyneuropathy. We performed a retrospective chart review of 143 patients who were started on pregabalin or duloxetine during a 10-month period in a tertiary neuromuscular outpatient center for neuropathic pain. Duloxetine and pregabalin were started in 103 and 91 patients, respectively. Ninety-two patients tried only one of the two medications while both medications were used at different time periods in 51 patients. Follow-up was available for 87 patients on pregabalin and 89 patients on duloxetine. More patients with neuropathic pain reported an improvement with pregabalin (33%) than duloxetine (21%). Duloxetine (38%) had a higher frequency of side effects compared to pregabalin (30%). However, these differences between pregabalin and duloxetine were not statistically significant. Despite the study's limitations of retrospective design, these findings suggest that both pregabalin and duloxetine are probably effective for neuropathic pain, secondary to diabetes or cryptogenic sensory peripheral neuropathy in a tertiary care academic neuromuscular center. Prospective randomized controlled comparative effectiveness studies are required for both drugs in the treatment of neuropathic pain.

Retrospective chart review of duloxetine and pregabalin in the treatment of painful neuropathy.

The frequency of ocular myasthenia gravis (OMG) in patients referred to an academic neuro-ophthalmology clinic for suspected myasthenia gravis is not known. Our objective was to determine the frequency of ocular OMG in patients referred to an academic neuro-ophthalmologist and determine alternate diagnoses and response to therapy.

Ocular myasthenia gravis in an academic neuro-ophthalmology clinic: clinical features and therapeutic response.

Facial onset sensorimotor neuronopathy (FOSMN) is a recently described neurological syndrome characterized by slow onset of facial sensory abnormalities and subsequent development of motor deficits. Except for 1 patient, FOSMN has so far been identified only in men.

Facial onset sensorimotor neuronopathy syndrome:  a case series.

To identify the frequency of leg amyotrophic diplegia (LAD) at a US academic center, describe the pattern of weakness, and provide comparative data from 8 additional major US academic institutions.

Leg amyotrophic diplegia: prevalence and pattern of weakness at US neuromuscular centers.

Pompe disease is a rare multi-systemic metabolic myopathy caused by autosomal recessive mutations in the acidic alpha glucosidase (GAA) gene. Significant progress had been made in the diagnosis and management of patients with Pompe disease. Here, we describe our experience with 12 patients with various forms of Pompe disease including 4 potentially pathogenic, novel GAA variants. We also review the recent the recent advances in the pathogenesis, diagnosis, and treatment of individuals with Pompe disease. 

Pompe disease: literature review and case series.

Myasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood.

A genome-wide association study of myasthenia gravis.

Dermatomyositis is a life-altering inflammatory disorder of skin and muscle. Details regarding the natural course of this disorder, the effects of specific therapies on its progression, and the optimal therapeutic dosage and duration of prednisone are limited. We performed a retrospective medical record review of dermatomyositis patients at four medical centers. All patients were over the age of 21 and had a clinical diagnosis of dermatomyositis with pathological confirmation. We reviewed average muscle strength, corticosteroid use, creatine kinase levels, and supplemental immunosuppressant use during the 36-month period following each patient's initial assessment. One hundred patients participated with an average age of 50.1 years. Average muscle strength improved and prednisone requirements lessened six months after initial assessment. There was no difference in the mean change in muscle strength or cumulative corticosteroid use over 36 months among those initially treated with methotrexate, mycophenolate mofetil, pulse IVIG, or azathioprine. There was a 5% mortality rate in dermatomyositis patients due to infections. Treated dermatomyositis patients demonstrate the most significant improvement in strength during the first six-to-twelve months following their initial clinical assessment. Additional prospective studies are needed to determine the relative benefit of select immunosuppressant agents in preserving strength and reducing corticosteroid use in dermatomyositis.

Disease course and therapeutic approach in dermatomyositis: A four-center retrospective study of 100 patients.

When approaching a patient with suspected motor neuron disease (MND), the pattern of weakness on examination helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing. MNDs exist on a spectrum, from a pure lower motor neuron to mixed upper and lower motor neuron to a pure upper motor neuron variant. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic, which is invariably fatal. This article describes a pattern approach to identifying MND and clinical features of sporadic ALS. 

Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis.

The number of available symptomatic treatments has markedly enhanced the care of patients with amyotrophic lateral sclerosis (ALS). Once thought to be untreatable, patients with ALS today clearly benefit from multidisciplinary care. The impact of such care on the disease course, including rate of progression and mortality, has surpassed the treatment effects commonly sought in clinical drug trials. Unfortunately, there are few randomized controlled trials of medications or interventions addressing symptom management. In this review, the authors provide the level of evidence, when available, for each intervention that is currently considered standard of care by consensus opinion. 

Symptom Management and End-of-Life Care in Amyotrophic Lateral Sclerosis.

The goals of this study were to characterize clinical and electrophysiologic findings of subjects with upper motor neuron disease and to explore feasibility of clinical trials in this population.

Primary Lateral Sclerosis and Early Upper Motor Neuron Disease: Characteristics of a Cross-Sectional Population.

Sporadic inclusion body myositis (sIBM) is the commonest severe myopathy in patients more than 50 years of age. Previous therapeutic trials have targeted the inflammatory features of sIBM but all have failed. Because protein dyshomeostasis may also play a role in sIBM, we tested the effects of targeting this feature of the disease. Using rat myoblast cultures, we found that up-regulation of the heat shock response with arimoclomol reduced key pathological markers of sIBM in vitro. Furthermore, in mutant valosin-containing protein (VCP) mice, which develop an inclusion body myopathy, treatment with arimoclomol ameliorated disease pathology and improved muscle function. We therefore evaluated arimoclomol in an investigator-led, randomized, double-blind, placebo-controlled, proof-of-concept trial in sIBM patients and showed that arimoclomol was safe and well tolerated. Although arimoclomol improved some IBM-like pathology in the mutant VCP mouse, we did not see statistically significant evidence of efficacy in the proof-of-concept patient trial. 

Targeting protein homeostasis in sporadic inclusion body myositis.

Understanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALS) will provide key information for optimising clinical trials in this patient population.

Defining SOD1 ALS natural history to guide therapeutic clinical trial design.

To compare the frequency of abnormalities in epidermal nerve fiber density (ENFD) and quantitative sudomotor axon reflex (QSART) in patients with diabetic distal symmetric polyneuropathy (DSPN).

Less is More in Diabetic Neuropathy Diagnosis: Comparison of Quantitative Sudomotor Axon Reflex and Skin Biopsy.

To estimate the satisfactory response rate (SR%) with achieving maintenance, low-dose prednisone in acetylcholine receptor antibody-positive generalized myasthenia gravis.

Article	Year
Myasthenia gravis, thymoma, and intestinal pseudo-obstruction: a case report and review. Journal of clinical neuromuscular disease\| PubMed ID: 19078726	2003
Clinical findings in MuSK-antibody positive myasthenia gravis: a U.S. experience. Muscle & nerve\| PubMed ID: 19882635	2010
Retrospective chart review of duloxetine and pregabalin in the treatment of painful neuropathy. The International journal of neuroscience\| PubMed ID: 21671841	2011
Ocular myasthenia gravis in an academic neuro-ophthalmology clinic: clinical features and therapeutic response. Journal of clinical neuromuscular disease\| PubMed ID: 22361625	2011
Facial onset sensorimotor neuronopathy syndrome: a case series. Journal of clinical neuromuscular disease\| PubMed ID: 22922575	2012
Leg amyotrophic diplegia: prevalence and pattern of weakness at US neuromuscular centers. Journal of clinical neuromuscular disease\| PubMed ID: 23965403	2013
Pompe disease: literature review and case series. Neurologic clinics\| PubMed ID: 25037089	2014
A genome-wide association study of myasthenia gravis. JAMA neurology\| PubMed ID: 25643325	2015
Disease course and therapeutic approach in dermatomyositis: A four-center retrospective study of 100 patients. Neuromuscular disorders : NMD\| PubMed ID: 26022999	2015
Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis. Neurologic clinics\| PubMed ID: 26515618	2015
Symptom Management and End-of-Life Care in Amyotrophic Lateral Sclerosis. Neurologic clinics\| PubMed ID: 26515628	2015
Primary Lateral Sclerosis and Early Upper Motor Neuron Disease: Characteristics of a Cross-Sectional Population. Journal of clinical neuromuscular disease\| PubMed ID: 26905909	2016
Targeting protein homeostasis in sporadic inclusion body myositis. Science translational medicine\| PubMed ID: 27009270	2016
Defining SOD1 ALS natural history to guide therapeutic clinical trial design. Journal of neurology, neurosurgery, and psychiatry\| PubMed ID: 27261500	2017
Less is More in Diabetic Neuropathy Diagnosis: Comparison of Quantitative Sudomotor Axon Reflex and Skin Biopsy. Journal of clinical neuromuscular disease\| PubMed ID: 28827483	2017
Satisfactory Response With Achieving Maintenance Low-Dose Prednisone in Generalized Myasthenia Gravis. Journal of clinical neuromuscular disease\| PubMed ID: 30439750	2018

April McVey

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