Hereditary inclusion-body myopathy associated with cardiomyopathy: report of two siblings.

Hereditary inclusion-body myopathy (HIBM) or distal myopathy with rimmed vacuoles (DMRV) is an autosomal recessive disorder characterized by preferential involvement of distal muscles in the lower extremities, especially the anterior compartment of the legs, with relative preservation of the quadriceps.This is referred to as quadriceps-sparing myopathy. Previous reports have revealed exclusive involvement in skeletal muscles. Herein we describe two siblings with typical HIBM/DMRV. The patients developed exertional dyspnea 20-26 years after disease onset. Echocardiogram revealed a cardiomyopathy in both patients. This is the first report of the association between HIBM/DMRV and cardiomyopathy.

A Case of Triple-Negative Myasthenia Gravis Lambert-Eaton Overlap Syndrome With Negative Agrin and LRP-4 Antibodies.

A case of triple-negative myasthenia gravis Lambert-Eaton overlap syndrome with negative Agrin and LRP-4 antibodies. Myasthenia gravis (MG) is an autoimmune disorder that shares similar features with Lambert-Eaton myasthenic syndrome. The combined clinical and electrophysiological findings of MG and Lambert-Eaton myasthenic syndrome have been reported, these cases represent the so-called "myasthenia gravis Lambert-Eaton overlap syndrome" (MLOS). A total of 55 MLOS cases have been identified, 13 cases were reported before the acetylcholine receptor (AChR) antibody (ab) testing era, 14 during the AChR-ab era, 26 during the voltage-gated calcium channel (VGCC)-ab era, and 2 cases have been reported during the muscle-specific kinase (MuSK)-ab era, of these; only 1 patient tested negative for all 3 antibodies. New immunological markers have been identified in the study of MG [Agrin and the low-density lipopro-tein receptor-related protein 4 (LRP-4)]. We present a patient with MLOS who tested negative for all 5 (AChR, MuSK, VGCC, Agrin, and LRP-4) serologic markers.

Neuromuscular complications in uremics: a review.

BACKGROUND: Uremia may be associated with various neurologic manifestations, particularly a polyneuropathy, but also with focal neuropathies such as carpal tunnel syndrome and shunt-related neuropathies. Myopathies can also be caused by uremia and its metabolic disarrangements. REVIEW SUMMARY: This article reviews the clinical presentation, pathogenesis, and treatment of uremic polyneuropathy, focal neuropathies, and uremic myopathies. CONCLUSION: Recognizing the presentation and pathogenesis of uremic polyneuropathies, mononeuropathies, and myopathies are important for their prevention and for proper management.

Dr. Aníbal Zambrano: un médico peruano con corazón de oro / Aníbal Zambrano, M.D: a Peruvian physician with a heart of gold

RESUMEN El objetivo del artículo es describir y analizar la trayectoria de vida y las contribuciones humanitarias del Dr. Zambrano, médico egresado de la Escuela de Medicina de San Fernando, quién fue presidente del Centro de Estudiantes de Medicina en una época políticamente álgida en la educación universitaria pública. Emigró a los Estados Unidos en 1970, bajo el contexto de crisis sociopolítica económica en el Perú y en el mundo, donde se convirtió en un renombrado médico internista y cardiólogo del St. Luke's Hospital. A pesar de su lejanía, mantuvo un lazo estrecho con el Perú organizando múltiples misiones médicas para el beneficio de poblaciones vulnerables, capacitación al personal médico e implementación tecnológica del Hospital Regional de Cajamarca. En 2011 se inauguró el Centro Médico Educativo en Chincha, siendo Zambrano uno de los líderes para su construcción. A pesar de padecer una enfermedad invalidante dedicó hasta los últimos días de su vida a brindar ayuda a los más necesitados. Su trayectoria de vida nos muestra un ejemplo de compromiso con el Perú y de un ejercicio de la medicina comprometida con la solidaridad y el desarrollo de la medicina en su país de origen.

ABSTRACT The objective of the article is to describe and analyze the life trajectory and the humanitarian contributions of Dr. Zambrano, a physician who graduated from San Fernando Medical school, and was president of the Center for Medical Students at a politically critical time in public university education. He emigrated to the United States in 1970, in the context of sociopolitical crisis in Peru and the world, where he became a renowned internist and cardiologist at St. Luke's Hospital. Despite the distance, he maintained a close relationship with Peru, organizing multiple medical missions for underserved populations, training medical personnel, and providing technological implementation to Cajamarca Regional Hospital. In 2011, the Educational Medical Center was inaugurated in Chincha, with Zambrano being one of the leaders for its construction. Despite suffering from a disabling illness, he dedicated until the last days of his life, providing help for those most in need. His life trajectory shows us an example of commitment to Peru and practice of Medicine committed to solidarity and the development of Medicine in his country of origin.

Somatic mosaicism due to a reversion variant causing hemi-atrophy: a novel variant of dystrophinopathy.

We describe a case of hemi-atrophy in a young adult male, with a positive family history of three maternal uncles with Duchenne muscular dystrophy (DMD). The patient showed progressive weakness localized to the left side, an abnormal electromyography, and creatine kinase levels >3000 IU/l. Muscle biopsy showed both dystrophin-positive and -negative myofibers. An out-of-frame duplication variant in DMD, that is, c.(93+1_94-1)_(649+1_650-1)dup(p.?) resulting in duplication of exons 3-7 was inherited, but the muscle biopsy showed dystrophin mRNA with and without the duplication. Dystrophin quantification using mass spectrometry showed 25% normal dystrophin protein levels in the muscle biopsy from the stronger right side. Sex chromosome aneuploidy was ruled out. We conclude that the patient inherited the duplication variant, but early in development an inner cell mass underwent a somatic recombination event removing the duplication and restoring dystrophin expression. To our knowledge, this is the first report of a reversion leading to somatic mosaicism in DMD.

Comparative Long-Term Evaluation of Patients With Juvenile Inflammatory Myopathies.

OBJECTIVES: We conducted a retrospective study analyzing the clinical features, laboratory findings, demographics, and long-term prognoses of patients with juvenile inflammatory myopathies to determine possible predictors indicating the use of aggressive immunotherapy and the response to and complications of treatment. METHODS: The medical records of 41 patients with juvenile inflammatory myopathies seen at University of Tennessee-affiliated hospitals in Memphis from 1969 to 2008 were evaluated. Patients' clinical characteristics, laboratory studies, muscle biopsies, and electromyography were reviewed. All patients were treated with prednisone initially; additionally, 14 patients received varying combinations of other immunosuppressant therapies. RESULTS: Seventy-three percent of the patients experienced remission. Patients in the group that did not go into remission had specific characteristics at onset: they were comparatively older and had more severe rashes, contractures, arthritis, and systemic involvement. Also, patients with positive autoantibodies (antinuclear antibody, rheumatoid arthritis factor) had better outcomes. CONCLUSIONS: Juvenile inflammatory myopathies have relatively good prognoses. Initial presentation at advanced age or with severe rash, systemic vasculopathies, anemia, or arthritis portends refractory disease; in these patients, second- and third-line therapies improve outcome.

Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.

BACKGROUND: Molecular diagnostics in the genetic myopathies often requires testing of the largest and most complex transcript units in the human genome (DMD, TTN, NEB). Iteratively targeting single genes for sequencing has traditionally entailed high costs and long turnaround times. Exome sequencing has begun to supplant single targeted genes, but there are concerns regarding coverage and needed depth of the very large and complex genes that frequently cause myopathies. OBJECTIVE: To evaluate efficiency of next-generation sequencing technologies to provide molecular diagnostics for patients with previously undiagnosed myopathies. METHODS: We tested a targeted re-sequencing approach, using a 45 gene emulsion PCR myopathy panel, with subsequent sequencing on the Illumina platform in 94 undiagnosed patients. We compared the targeted re-sequencing approach to exome sequencing for 10 of these patients studied. RESULTS: We detected likely pathogenic mutations in 33 out of 94 patients with a molecular diagnostic rate of approximately 35%. The remaining patients showed variants of unknown significance (35/94 patients) or no mutations detected in the 45 genes tested (26/94 patients). Mutation detection rates for targeted re-sequencing vs. whole exome were similar in both methods; however exome sequencing showed better distribution of reads and fewer exon dropouts. CONCLUSIONS: Given that costs of highly parallel re-sequencing and whole exome sequencing are similar, and that exome sequencing now takes considerably less laboratory processing time than targeted re-sequencing, we recommend exome sequencing as the standard approach for molecular diagnostics of myopathies.

An Overview of Laryngeal Muscle Single Fiber Electromyography.

Needle electromyography is an important tool in the diagnosis of neuromuscular diseases and has also been applied successfully in the evaluation of the vocal cord paralysis. Laryngeal electromyography, initially described by Weddell, is used to determine the cause of vocal cord paralysis and to differentiate organic from nonorganic causes of speech disorders. This test allows the diagnosis of lower motor neuron and nerve paralysis as well as myopathies. Laryngeal electromyography also helps to determine the prognosis of paralysis caused by traumatic injury of the laryngeal nerves and is used for guidance during botulinum toxin injection in spasmodic dysphonias. Single fiber electromyography is used to diagnose abnormalities of neuromuscular transmission and is applied in the study the architecture of the motor unit in muscles. This article reviews the techniques of laryngeal muscles single fiber electromyography, provides limited informative data, and discusses its potential value in the evaluation of patients with dysphonia.

Perisurgical management of patients with neuromuscular disorders.

Patients with neuromuscular disorders who undergo surgical procedures are particularly predisposed to complications during the perioperative period. Such complications may arise from respiratory failure, arrhythmias,or infections, and particularly MH. It is recommended that these patients be monitored for respiratory and cardiovascular complications and receive proper respiratory toilet, physio-therapy, and incentive respirometry. Proper electrolyte balance is mandatory. They should be monitored in the ICU when necessary. Excessive sedation of these patients, and drugs that could aggravate weakness or cause MH, should be avoided. Those at risk of MH should not receive drugs that may precipitate an attack.

Neurologic complications of disorders of the adrenal glands.

Disorders of the adrenal glands frequently have secondary neurological manifestations, while some diseases that involve the central nervous system are accompanied by adrenal gland dysfunction. Excessive corticosteroid secretions in primary or secondary Cushing's syndrome causes muscle weakness and behavioral disturbances, such as emotional lability and sometimes depression, while adrenal insufficiency may cause fatigue, weakness, and depression. Adrenoleukodystrophy and adrenoneuromyelopathy are X-linked recessive disorders of the metabolism of very long chain fatty acids that manifest with white matter abnormalities of the brain, myelopathy and/or neuropathy, as well as adrenal insufficiency. Other disorders of the adrenal glands include hyperaldosteroidism, which may cause weakness from hypokalemia. Dysfunction of the adrenal medulla causes excessive or deficient secretion of catecholamines, primarily causing cardiovascular symptoms. This chapter reviews the clinical manifestations and diagnostic aspects and treatment of the various disorders of the adrenal glands. Some of the congenital adrenal diseases are also discussed.

An adult male with progressive spastic paraparesis and gait instability.

This is a case of an adult male with history of motor difficulties, speech, and behavioral problems since early childhood found to have progressive spastic paraparesis, impaired vibration and proprioception, and gait instability. His medical history included bilateral cataracts status post surgical removal at the age of 30, cholelithiasis status post cholecystectomy at age 45, and high cholesterol levels.

A male with progressive lower extremity weakness and monoclonal gammopathy.

EDUCATIONAL OBJECTIVES: To discuss a case of progressive lower extremity paresis and paresthesias in a patient found to have monoclonal gammopathy. KEY QUESTIONS: (1) What is the differential diagnosis of progressive lower extremity paresis and paresthesias? (2) How would one approach diagnostic testing for such a patient? (3) What is the differential diagnosis of neuropathy associated with gammopathy? and (4) What is the treatment for this patient?

Dermatomyositis presenting with focal scleroderma-like skin changes.

OBJECTIVE: To describe an unusual focal scleroderma-like skin changes in patient with dermatomyositis. METHODS: Review of clinical records, laboratory investigations, and muscle and skin biopsies. RESULTS: The patient developed unusual skin lesions characterized by symmetrical atrophy and hardening of focal skin and muscle over the lateral upper arms and posterior shoulders, and the left temporal and pectoral areas. Extensive blood work-up for scleroderma and other connective-tissue diseases was negative. A skin biopsy showed distinct pathologic features including increased interstitial mucin, hyperpigmentation, and perivascular lymphocytic inflammation without severe fibrosis. The scleroderma-like skin changes and muscle weakness improved with immunotherapy. CONCLUSIONS: Dermatomyositis can manifest with focal scleroderma-like skin changes clinically and reticular erythematous mucinosis-like changes pathologically, and these distinct skin changes represent a new variant of skin lesions of dermatomyositis.

Limb edema and anasarca associated with severe dermatomyositis: report of four cases.

Dermatomyositis is an autoimmune disorder that causes proximal muscle weakness and skin changes which include generalized erythema, heliotrope rash and/or Gottron's papules. Generalized or limb edema is an uncommon manifestation of dermatomyositis. Here, we report four cases who presented with generalized or limb edema, proximal muscle weakness, erythematous skin rash and/or dysphagia. Muscle biopsy revealed perifascicular fiber atrophy, a characteristic finding of dermatomyositis. The absence of other causes indicated that the generalized or limb edema was caused by dermatomyositis. None of our patients showed significant improvement with steroids alone, and more aggressive immunotherapy eventually resolved the edema. We concluded that generalized or limb edema may be a hallmark of a severe form of dermatomyositis and requires prompt and aggressive therapies.

Effects of 3-4 diaminopyridine (DAP) in motor neuron diseases.

OBJECTIVE: To study the safety of 3-4 diaminopyridine (DAP) in patients with motor neuron diseases and to examine its efficacy in reducing muscle fatigue and weakness and in improving objective parameters of muscle function. DESIGN: Assessments of safety included a questionnaire of symptoms, clinical examination, blood testing, and electrocardiography at each visit; efficacy was assessed by subjective scores of fatigue and weakness; an Amyotrophic Lateral Sclerosis Functional Rating Scale and functional ability scores, including timed verbal scores; manual muscle testing; grip dynamometry; pulmonary function tests; timed functional tests; and electrophysiological studies. PARTICIPANTS: Thirteen subjects with amyotrophic lateral sclerosis and seven subjects with only a lower motor neuron syndrome. MAIN OUTCOMES: Assess tolerability of DAP and determine if there was symptomatic improvement of muscle fatigue. SECONDARY OUTCOME: To determine the effects of DAP on objective parameters of muscle function. RESULTS: The drug was well tolerated with only four subjects reporting tingling of lips and fingers during the active drug period. The subjective scores for fatigue and weakness showed a mild improvement after 4 weeks on DAP compared with placebo. A significant benefit of DAP was also demonstrated in the timed verbal scores. CONCLUSION: 3-4 DAP appeared to be safe and produced subjective benefit in motor neuron diseases. The drug could be added for symptomatic treatment in these diseases. Larger studies are necessary to demonstrate efficacy.

A female with progressive four-limb paresthesias and gait difficulty.

EDUCATIONAL OBJECTIVES: To discuss a case of progressive four-limb paresthesias and gait difficulty in a female who had previously undergone gastric bypass surgery. KEY QUESTIONS: 1) What is the differential diagnosis of progressive four-limb paresthesias and gait difficulty? 2) How would one approach diagnostic testing for such a patient? 3) What are the complications of gastric bypass surgery? 4) What is the treatment for this patient?

Artifact on electromyography produced by an implanted sacral nerve stimulator.

A patient with muscle cramps was referred for nerve conduction studies and electromyography. Her study demonstrated bursts of spontaneous electromyography activity, which waxed and waned in amplitude with a "dive bomber"-like sound. The abnormal finding was found to be an artifact from an implanted sacral nerve stimulator for bladder incontinence.

Transient neonatal myasthenia gravis in a baby born to a mother with new-onset anti-MuSK-mediated myasthenia gravis.

We describe a 30-year-old pregnant woman with undiagnosed weakness who delivered a severely weak neonate. Subsequent workup of the mother revealed myasthenia gravis with muscle-specific kinase antibodies. The infant responded to intravenous immunoglobulin and symptoms normalized. He was presumed to have an anti-muscle-specific kinase-mediated transient neonatal myasthenia gravis.

Leucoencephalopathy, transverse myelopathy, and peripheral neuropathy in association with glutamic acid decarboxylase-65 (GAD) antibodies in children with cancer.

Neurologic toxicity may occur as a direct effect of cancer and its therapy or indirectly because of a dysfunctional immune system. The authors report the development of axonal neuropathy, myelopathy, and leucoencephalopathy associated with glutamic acid decarboxylase-65 (GAD) antibodies in 4 children with progressive cancer who were heavily pretreated. Three patients with refractory leukemia and 1 with Ewing sarcoma developed paraplegia with sensory level and dorsal column dysfunction. Three developed leucoencephalopathy and 1 died of neurologic disease. All had high serum titers of GAD antibodies during the progressive phase of the illness, and the antibody levels returned to normal with the stability of the neurologic disease. Three survivors are showing gradual recovery. This syndrome of central and peripheral nervous system toxicity may have resulted from chemotherapy toxicity or from immune dysfunction, as suggested by the high GAD antibody titers.

Diffusely increased insertional activity: "EMG disease" or asymptomatic myotonia congenita? A report of 2 cases.

The term "EMG disease" is used by some to describe the unexpected finding of diffusely increased insertional activity on needle electromyography in an otherwise asymptomatic person. The cause is unknown, but it has been hypothesized that these patients actually have a subclinical myotonic disorder. We describe 2 patients with diffusely increased insertional activity on electromyography who had mutations of the CLCN1 gene associated with myotonia congenita. Neither patient had symptoms or reproducible signs of this disorder. We propose that asymptomatic patients with CLCN1 mutations may at least partially account for the EMG disease phenotype.