[Charcot-Marie-Tooth disease. Peroneal muscular atrophy]. / Charcot-Marie-Tooths sykdom. Peroneal muskelatrofi.

The classification of Charcot-Marie-Tooth disease is provisional, because the chromosome and gene localization is still not precisely known, and gene products have not been identified. This article presents an analysis of the clinical, genetical and neurophysiological data of eight Charcot-Marie-Tooth patients. The study was carried out to find out if it is possible to classify the disease from neurophysiological and genetical data. We found Charcot-Marie-Tooth disease transmitted autosomal dominant in three cases, whereas no family pattern was apparent in the remaining five. Among the three cases of autosomal dominant transmission, two were of the segmental demyelinization type, and one had axonal neuropathy. The five patients without a distinct family pattern consisted of three with segmental demyelinization and two with axonal neuropathy. Thus, the neurophysiological subdivision did not correlate with the inheritance, which indicates a genetical heterogeneity for the Charcot-Marie-Tooth disease.

Fat infiltration, atrophy and hypertrophy of skeletal muscles demonstrated by X-ray computed tomography in neurological patients.

Since 1982, we have used X-ray computed tomography (CT) to study the skeletal muscles of neurological patients. We present here the findings in 23 patients with myogenic and 29 patients with neurogenic diseases. The method is convenient to demonstrate fat infiltration, atrophy and hypertrophy of skeletal muscles, but is of little help in differentiating between the 2 disease categories or individual diagnoses. The maximal isometric voluntary force of m. quadriceps femoris was measured in 13 of the patients with neurogenic, and in 10 of the patients with myogenic diseases. The power was compared with the cross-sectional area and the structural changes observed in the parenchyme of the muscles in the CT scans. A positive correlation was found between the size and the force of the muscle in both patient groups. The appearance of the muscular parenchyme was of little help to predict its function.

Conchotome and needle percutaneous biopsy of skeletal muscle.

Percutaneous muscle biopsy is an important and acceptable technique in the study of conditions involving human skeletal muscle. A review of 436 conchotome and needle muscle biopsies obtained over 18 months in this centre is presented.

Primidone and propranolol in essential tremor: a study based on quantitative tremor recording and plasma anticonvulsant levels.

Primidone was compared to the unselective beta adrenoceptor antagonist propranolol in the suppression of essential tremor. In a 4-week single-blind placebo-controlled study primidone was given in increasing doses from 62.5 mg X 1 up to 250 mg X 3 daily and propranolol 20 mg X 3 daily. The drugs produced a similar reduction in the degree of tremor after 2 and 1 weeks' medication respectively. This indicates that primidone can be an alternative to propranolol when beta-blockers are contraindicated. However, primidone was significantly even more effective in the beginning after only 2 doses, when at the same time 10 of 13 patients showed a maximum of acute toxic side-effects producing nausea, vomiting, giddiness and/or sedation. Correlation analysis between the individual tremor amplitude reductions and plasma primidone concentrations showed on the second day a tendency towards a greater reduction in tremor in those patients with the highest primidone plasma concentration. By the fourteenth day tremor had increased compared with the second day and correlation analysis between individual increase in tremor amplitude and plasma phenobarbital concentrations showed the highest degree of tremor increase in those patients who had the highest levels of phenobarbital. These and other data suggest that after the first doses, tremor suppression and acute toxicity is related to the initial exposure to primidone and the plasma level of the drug itself rather than its metabolites phenobarbital and phenylethylmalanomide. The individual tremor frequency spectrums did not change significantly during the placebo and propranolol periods, whereas the frequency tended to decrease during the primidone period.

Familial combined deficiency of muscle carnitine and carnitine palmityl transferase (CPT).

Two patients, brother and sister, aged 19 and 16, with combined, partial deficiency of carnitine palmityltransferase (CPT) are reported. Both patients had recurrent exercise-related myoglobinuria. The brother had also experienced an episode of transient renal failure associated with myoglobinuria. Both had elevated CK and myoglobin in plasma between attacks. There was a normal production of lactate in ischaemic forearm exercise, but elevated levels of NH3, resulting in an increased NH3/lactate ratio; 48-h fasting caused no significant changes in cholesterol, triglycerides or glucose, no rise of CK, and a normal ketogenic response, indicating no hepatic enzyme deficiency. Muscle biopsy showed slight changes of myopathy in both patients, with scattered atrophic fibres, but no lipid accumulation or other specific changes. Biochemical analysis of muscle tissue revealed a reduction of carnitine to 48% and 40% and a reduction of CPT to 55% and 59% of normal values, which is similar to the findings in the only previous report of combined partial carnitine and CPT deficiency. The heterogeneity of the laboratory findings in CPT deficiencies and the value of the various diagnostic procedures in metabolic myopathies are discussed.

Late-onset hereditary myopathy with abnormal mitochondria and progressive dementia.

A family with autosomal dominant late-onset progressive dementia and myopathy is described. Electron microscopy of muscle revealed abnormal mitochondria in the proband. Thus, the disease may be classified as a "mitochondrial encephalomyopathy". The cases are unique because dementia was a dominating feature and because the symptoms developed late in life. These cases may represent a new subgroup of the mitochondrial encephalomyopathies.

Effect of clorazepate in spasticity and rigidity: a quantitative study of reflexes and plasma concentrations.

The effect on increased myotatic reflexes of desmethyldiazepam, formed from its precursor clorazepate, was assessed in a double-blind cross-over study of 27 days duration. Eight patients with spasticity or rigidity were given placebo or active substance; first in loading doses for 2 days, then 5 mg every 12 h for a total of 10 days. A wash-out period of 7 days was interposed between the 2 10-day periods. Desmethyldiazepam had a normalizing effect on the increased phasic ankle reflexes seen in spasticity, but not on the increased tonic reflex seen in rigidity. The mean concentration of desmethyldiazepam in the steady state was 1227 nmol/l (range 600-1990 nmol/l). The plasma concentration of desmethyldiazepam tended to correlate with the percent decrease in phasic reflex activity (P = 0.08, 2-tailed). A slight drowsiness in 2 patients was the only side-effect seen. In conclusion, desmethyldiazepam given as clorazepate seems to be a suitable medicament in the treatment of spasticity.

Lymphocyte capping: a diagnostic method in progressive muscular dystrophy?

Recent observations indicate that antibody-induced redistribution ("capping") of membrane antigens of B-lymphocytes is subnormal in patients with progressive muscular dystrophy. The present study was primarily designed to verify or refute claims that such an abnormally low capping capacity can be used to diagnose this disease group. In eight dystrophy patients we found the median capping to be reduced to 40%, while it was 52% in 27 neurological control patients, and 62% in 20 healthy blood donors. However, there was considerable overlap between the capping percentages of the three groups. Thus, our data indicate that the demonstration of reduced lymphocyte capping in the individual patient is of little, if any, diagnostic value.

Effects of timolol and atenolol on benign essential tremor: placebo-controlled studies based on quantitative tremor recording.

Two different beta-adrenoreceptor antagonists, atenolol and timolol, were separately compared with a placebo in the suppression of essential tremor. In two-week single-blind placebo-controlled studies with cross-over, timolol (5 mg twice daily) and atenolol (100 mg once daily) produced an equal reduction in sitting heart rate and sitting blood pressure. Timolol was effective in reducing tremor while atenolol failed to reduce tremor amplitude. These results indicate that essential tremor can be reduced but not blocked, by the adrenergic blocker timolol with both beta 1 and beta 2 blocking properties; but not by the relatively selective beta 1 blocking drug atenolol. Possibly, the tremor reduction is medicated by a peripheral effect on beta 2 adrenoreceptors.

Effect of diazepam and desmethyldiazepam in spasticity and rigidity. A quantitative study of reflexes and plasma concentrations.

Benzodiazepines are known to reduce increased muscle stretch reflexes. To investigate the relationship between the necessary plasma concentrations of diazepam and its major metabolite desmethyldiazepam on the one hand and the phasic and tonic ankle reflex activity on the other, 10 mg diazepam was given intravenously to nine patients, seven with spasticity due to multiple sclerosis and two with parkinsonian rigidity. Diazepam and desmethyldiazepam both had a normalizing effect on the increased phasic ankle reflex seen in spasticity. No effect was observed on the increased tonic reflexes in rigidity. The concentrations of diazepam necessary to reduce spasticity ranged between 300-2,200 mg/l and were so high that drowsiness did occur. However, the study may indicate that desmethyldiazepam has a higher potency and a more long lasting effect on the increased phasic reflexes than diazepam.

Treatment of parkinsonism with l-dopa and a decarboxylase inhibitor. An electrophysiological and clinical study.

Twelve parkinsonian patients with an unsatisfactory therapeutic result on L-Dopa alone due to nausea, vomiting and involuntary movements were treated WITH L-Dopa and decarboxylase inhibitor. The daily dose reached 800mg L-Dopa and 200 mg decarboxylase inhibitor. Single doses of each of the components were also given. Electrophysiological examination of hypokinesia, tremor and rigidity, and clinical observation revealed clear evidence of rapid improvement on small doses of L-Dopa combined with decarboxylase inhibitor. Most of the improvement occurred during the 1st week before the maximal dose was reached. A single oral dose of decarboxylase inhibitor resulted in an improvement, suggesting the presence in the organism of a small AMOUNT OF L-Dopa. This work also shows the absence of liver toxicity of the drug used. Elimination of the extracerebral side effects nausea and vomiting in our opinion is a principle advantage of the compound compared to L-Dopa alone, wheras abnormal involuntary movements, which were found in all patients, remain the limiting adverse side effect.