Masanori Igarashi

CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy

We tested the efficacy and safety of glutamine (0.6gm/kg/day) and creatine (5gm/day) in 50 ambulant boys with Duchenne muscular dystrophy in a 6‐month, double‐blind, placebo‐controlled clinical trial. Drug efficacy was tested by measuring muscle strength manually (34 muscle groups) and quantitatively (10 muscle groups). Timed functional tests, functional parameters, and pulmonary function tests were secondary outcome measures. Although there was no statistically significant effect of either therapy based on manual and quantitative measurements of muscle strength, a disease‐modifying effect of creatine in older Duchenne muscular dystrophy and creatine and glutamine in younger Duchenne muscular dystrophy cannot be excluded. Creatine and glutamine were well tolerated. Ann Neurol 2005;58:151–155

Pharmacologic treatment of childhood migraine

This review of pharmacologic treatment of childhood migraine shows that no agent for abortive treatment has been proved effective in controlled studies and that most commonly used prophylactic agents (e.g., propranolol and cyproheptadine) lack proof of their effectiveness. Flunarizine seems to be the only agent with positive results in controlled studies. This drug, although well tolerated, is slow to act. For the treatment of an acute attack, aspirin or acetaminophen may be chosen. Two of us currently use propranolol as the first-choice prophylactic agent because of its tolerance and cost, and on the assumption of its effectiveness reported by the adult studies. For children with a history of asthma, metoprolol may be chosen because of its selective blocking of the beta 1-adrenoreceptor. One of us (W.N.M.) prefers cyproheptadine as the drug of choice. Behavioral therapy may be a good alternative to pharmacotherapy in the management of childhood migraine.

Floppy infant syndrome.

Floppiness/hypotonia is a common neurologic symptom in infancy. A variety of neuromuscular disorders and central nervous system (CNS) disorders cause floppy infant syndrome (FIS). CNS disorders are the much more common causes of the syndrome than neuromuscular disorders. On long-term follow up, cerebral palsy and mental retardation turn out to be the 2 most common causes of FIS. This review focuses on neuromuscular causes of FIS. With the advent of molecular diagnosis, a few conditions can be diagnosed by DNA analysis of the peripheral lymphocytes (myotonic dystrophy, spinal muscular atrophy); however, for the most part, electrodiagnostic studies and muscle biopsy remain as essential diagnostic tools for FIS. Immunohistochemical study of the biopsied muscle also improves diagnostic capability. Management for most conditions remains supportive.

Cerebrovascular complications in children with nephrotic syndrome

Although the nephrotic syndrome is known to be a hypercoagulable state, cerebral arterial thrombosis associated with the nephrotic syndrome is an uncommon yet treatable cause of stroke syndrome in children. We report 2 children, 1 with congenital nephrotic syndrome and the other with minimal change nephrotic syndrome, who developed cerebral arterial thrombosis. The complication was fatal in 1 patient.

Diltiazem in the treatment of calcinosis in juvenile dermatomyositis.

Subcutaneous calcifications occur in a variety of diseases, including juvenile dermatomyositis. These calcifications cause disabling symptoms that do not always respond to immunosuppressant therapy. The calcium antagonist diltiazem reduces subcutaneous calcifications in CREST syndrome and in isolated cases of children with dermatomyositis. Our study was performed to determine the effects of diltiazem when used as adjunctive therapy in children with dermatomyositis.

A fatal presentation of dermatomyositis with facial swelling

Juvenile dermatomyositis (JDM) is the most common inflammatory autoimmune myopathy in children. Most common presentations consist of heliotrophic rash and/or gottrons papules in addition to proximal muscle weakness. A typical presentations have been reported. We present a 13-year-old African American male who presented with a two-week history of bilateral periorbital edema that was unresponsive to glucocorticoids. He had elevated transaminases but no detectable muscle weakness. A muscle biopsy was consistent with juvenile dermatomyositis. This case highlights the need to consider dermatomyositis in cases of facial swelling and the use of aggressive immunosuppressive therapies due to its associated vasculopathies.

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.

Congenital muscular dystrophy presenting with respiratory failure

Respiratory failure is an unusual initial manifestation of congenital muscular dystrophy. The authors describe a case of congenital muscular dystrophy in a patient presenting with rhabdomyolysis at birth. Despite an initially poor prognosis, aggressive respiratory therapy during the neonatal period permitted normal subsequent development. The muscular dystrophy predominantly involved the respiratory muscles.

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.