José Antonio Levy

Dystrophin immunofluorescence pattern in manifesting and asymptomatic carriers of Duchenne's and Becker muscular dystrophies of different ages☆

In order to investigate if the same apparent decrease in dystrophin negative fibers with aging observed in mouse mdx female heterozygotes also occurs in carriers of the DMD and BMD gene, we have studied the muscle of 29 DMD carriers (19 adults and 10 young daughters of obligate carriers, including 3 manifesting carriers) and 5 adult asymptomatic heterozygotes for Becker dystrophy (BMD). All young DMD possible carriers and 11 of 24 adult DMB/BMD heterozygotes had increased serum enzymes activities. A population of dystrophin negative fibers, more evident with the use of the C-terminal antibody, was seen in the three manifesting and in a 9-yr-old possible DMD carrier. In the remaining females, a positive immunohistochemical pattern of dystrophin, which did not differ from normal controls, was observed. Our results suggest that: (1) the increased population of dystrophin negative fibers reported in young mdx female heterozygotes was not seen in young DMD carriers, aged 6-17 yr; and (2) abnormalities in dystrophin immunostaining are not easily observed and are more frequent in manifesting carriers, when the muscle is grossly altered.

Emery-Dreifuss muscular dystrophy: anatomical-clinical correlation (case report)

We report on a man that had weakness of humeroperoneal distribution associated with limited range of motion of the cervical spine and elbows since he was 5 years old. At age 26 he developed tachycardia episodes. A complex arrhythmia was discovered, and a nodal ablation was done with a cardiac pacemaker implanted. The patient had an arrhythmia and sudden death followed this. Emery-Dreifuss muscular dystrophy is a rare recessive X-linked muscular disorder where mixed patterns in electromyography and muscle histology (neurogenic and/or myopathic) have caused nosological confusion. The autopsy findings are here described and correlated to the clinical features in an attempt to better understand the ambiguous findings concerning the process etiology.

Scleroderma associated with continuous electric muscular activity

The case of a 15-year-old male patient, suffering from difficulty in moving his arms and opening his mouth and dyspnea which had been slowly developing for two years, is reported. The neurologic examination revealed diffuse hypertonus, predominating in some muscle groups, compelling the patient to assume abnormal attitudes and making it impossible for him to open his mouth and to breathe freely due to a large decrease in the thoracic expansibility. The electromyographic studies showed continuous muscle activity at rest, characterized by high frequency discharges, which continued after anesthetic blocking of a peripheral nerve and after general anesthesia; these discharges were eliminated only when curare was used. Diagnosis was made of scleroderma and myositis, although only the first one could be confirmed by biopsy; the patient was treated with corticosteroids and a slight improvement was evidenced, specially in regard to breathing movements and mouth opening. Based on the good results reported by Isaacs in two similar cases, the authors used sodium hidantoinate, and thus found a marked decrease of the abnormal electric activity, proved though an electromyographic examination made some days afterwards.

Merosin-positive congenital muscular dystrophy in two siblings with cataract and slight mental retardation

We report on two siblings that have been followed for 14 years, with merosin-positive congenital muscular dystrophy (CMD), cataract, retinitis pigmentosa, dysversion of the optic disc, but no cerebral anomalies, except for microcephaly and slight mental retardation (MR). The younger child had three generalized seizures easily controlled by anticonvulsant therapy. Both children presented hypotonia from birth, delayed psychomotor development, generalized muscular weakness, and atrophy and joint contractures of knees and ankles. The course of the disease, apparently static during the first 10 years of life, became progressive during the second decade with loss of deambulation by the age of 13. Creatine kinase was increased in both children. Bilateral cataract was diagnosed at 6-months of age. In spite of the occurrence of microcephaly, MR was slight and the siblings acquired reading and writing skills after the aged 10. Head magnetic resonance imaging showed normal results in both siblings. The classification of these cases within the broad spectrum of CMD is difficult since most of the known muscle-eye-brain syndromes generally show severe MR and brain anomalies. We consider these cases as corresponding to the rarer syndromes of merosin-positive CMD with associated features such as cataract and MR that were particularly emphasized during the 50th ENMC International Workshop on CMD [Dubowitz V. Workshop report: 50th ENMC International workshop on congenital muscular dystrophy. Neuromusc Disord 1997;7:539-547]. Further genetic, pathological, neuroradiological, and immunocytochemical studies will be necessary for better elucidation of the classification and pathogenesis of CMD.

Sindrome de irritabilidade muscular aumentada: tratamento com nifedipina. Registro de um caso

In 1980 Alberca et al. described a patient with a syndrome of increased muscle irritability, who presented ondulating muscle rolling movements and electrically silent cramps, myoedema and muscle reactions to mechanical stimulation similar to myotonic response, suggesting a disfunction at myofibrillar level. We saw a similar case, of a male patient, 21 years of age, who complained of cramps of severe intensity for the past four years. These cramps were painful in the upper and lower limbs and impaired his locomotion; they were electrically silent. At percussion the patient showed severe idiomuscular contraction, with a period of increased relaxation, similar to a myotonic reaction and also, prolonged myoedema and rolling muscle contractions. Electromyography was normal, as were histochemical and electron microscopy studies. We carried out a therapeutic trial with niphedipine (a calcium antagonist), on the assumption that the patient showed a disturbance of the myofibrillar function--even though physiopathogenesis of the hyperirritability muscle syndrome was not yet clearly defined--and with a basis on the importance of the intracytoplasmatic level of Ca++ free in the muscle contraction mechanism, not only as the initiating factor of the contractile process, but also as a quantitative controller of the mechanic tension development through regulation of the amount of ATP metabolized during muscle activity. Administration of the drug in a dose of 40 mg daily, per os, brought a remission of the symptoms after two weeks, and the patient could walk normally again. On the introduction of a placebo, on two different opportunities, there occurred a recrudescence of the symptoms after about one weeks time.(ABSTRACT TRUNCATED AT 250 WORDS)Em 1975 Torbergsen 1 3 descreveu, em 5 pacientes de uma familia, uma doenca hereditaria dominante caracterizada por caimbras, contracoes musculares clinicamente semelhantes a miotonia, mioedema, contracoes musculares ondulantes desencadeadas por estimulos mecânicos e hipertrofia muscular. Exceto pela enzina creatinofosfoquinase (CPK) discretamente elevada, todos os exames complementares realizados foram normais, incluindo biopsia muscular e eletromiografia (EMG). Esta mostrou silencio eletrico durante as contracoes musculares involuntarias. Em 1980, Alberca et col.1 descreveram um paciente que apresentava caimbras em membros inferiores ao iniciar exercicios, respostas musculares a estimulacao mecânica semelhantes a miotonia, mioedema e movimentos ondulantes dos musculos, alem de sindrome cerebelar por atrofia de cerebelo, provavelmente nao relacionada com os demais sintomas descritos. Alem da CPK discretamente elevada, nenhuma outra alteracao laboratorial foi observada, mesmo nos estudos histoquimicos, de microscopia eletronica, e de EMG, que mostrou silencio eletrico durante as contracoes musculares involuntarias. Os autores consideraram o caso semelhante ao descrito por Torbergsen, com aparente apresentacao esporadica e com manifestacoes cerebelares associadas.

Chondrodystrophic myotonia: electromyographic and cardiac features of a case

The Schwartz‐Jampel syndrome or chondrodystrophic myotonia is a rare disease characterized by dwarfism, diffuse osteoarticular alterations, ble‐pharospasm, perioral muscular contractions and electromyographic alterations. The authors present a case of chondrodystrophic myotonia focusing mainly on facial electromyographic and cardiac findings. The electromyo‐graphy of the orbicularis oculi muscles showed abundant myotonic discharges like other facial muscles as well as muscles of the members. It was not possible to obtain true electrical silence between myotonic discharges, suggesting that the blepharospasm is a consequence of persistent muscular contraction. No conclusive evidence of myocardiopathy was given by clinical or laboratory cardiac examinations. General characteristics of the syndrome are discussed as well as the treatment with procamide and phenytoin.

Cardiopulmonary exercise testing for evaluation of muscle diseases

PURPOSE To evaluate the cardiopulmonary exercise testing (CPX) for the diagnosis of myopathies. METHODS 27 patients with myopathy were submitted to CPX testing (symptom limited bike protocol). RESULTS Dystrophic patients and patients with mitochondrial disease, compared with controls, showed significant differences for the power of work perfomed (watt) and the maximum oxygen consumption (VO2 max). Patients with mitochondrial disease presented significantly lower values of anaerobic threshold when compared to controls and elevation of exercise peak respiratory exchange ratio (RER) values when compared to the others groups. CONCLUSIONS CPX testing may be useful in evaluating degree of physical limitation of patients with myopathy at inicial stage as well on follow-up examinations. Power of work performed, VO2 max, anaerobic threshold and RER at exercise peak may suggest the diagnosis of myopathy and its sub-types and therefore exclude psychologic causes of limitation.

Resultados preliminares do emprêgo do ACTH nas degenerações combinadas da medula

Report on the immediate results of the use of ACTH in 4 cases of achylic demyelinating neuropathy. This treatment is justified by the possible allergic pathogenesis of the primary demyelinating processes. Dayly dosis of 12.5 mgm of corticotropin were given by continuous drip method, without any other associated drug which could interfere in the results. These were estimated on a semi-quantitative basis and evidenced slight beneficial effects of the hormone, which averaged 28.8 per cent. The accurate evaluation of the effects of corticotropin in subacute combined degeneration of the cord demands larger experience, based on greater number of cases and follow up of the patients, as well as the comparative study of such effects and the results obtained with classic treatment (liver extract, folic acid and vitamin B12).

Charcot-Marie-Tooth disease: current clinico-pathological concept

After some considerations on the pathologic picture of the Charcot-Marie-Tooth disease, the author reports the clinic and histopathologic (biopsy) features of four cases. According to the authors views this disease may be considered as a neuromyopathy owing to its histologic changes, either primarily muscular or secondary to the motor nerve lesion.

Miopatias associadas a agregados tubulares

The authors report the case of a 58-year-old male patient with clinical and electromyographic features of myasthenia. Muscle biopsy with histochemistry and electronic microscopy made it possible to diagnose a myopathy associated with tubular aggregates. Attention is called to the fact that the anatomical pathologic alterations which were found may be present in a heterogenous group of patients showing a great variety of symptoms. Thus, there is no reason to consider the existence of a myopathy associated with tubular aggregates, since the anatomical and pathologic findings are inespecific and do not characterize any specific disease.