N. Telerman-Toppet

Central core disease: A study of clinically unaffected muscle

Abstract Bilateral pes cavus in a 48-year-old women, with no muscle weakness, was the sole manifestation of central core disease. Characteristic histological changes were found in gastrocnemius and in the clinically unaffected biceps brachii. Histochemical observations confirmed the exclusive location of central cores in type I fibres. In type II fibres there was progressive atrophy and rarefaction, either by longitudinal splitting or by conversion from type II to type I. Increased collateral branching of subterminal motor axons supports the hypothesis of the neurogenic nature of the disease. Both central cores and targets may represent stages of a non-specific metabolic disorder occurring within restricted areas of fibres having high mitochondrial enzyme activity.

Cimetidine Interaction with Carbamazepine

Excerpt To the editor: A recent report of Desmond and colleagues (1) showed delayed clearance of diazepam due to cimetidine. Similar interactions of cimetidine have been mentioned with antipyrine, ...

The early stages of neuromuscular regeneration after crushing the sciatic nerve in the rat. Electrophysiological and histological study

Abstract Crushing of the sciatic nerve was performed on 84 rats and the functional recovery, reinnervation and distribution of fibre types were studied at short intervals between the crush and the 133rd day. The amplitude of evoked muscle potentials increased from the 25th day and regained a normal value after the 42nd day. Evidence of reinnervation of muscle fibres was observed as early as the 14th day. Apparently complete reinnervation was seen in some muscles 33 days after the crush. Type-grouping took place from the 42nd day; it was preceded from the 28th day by a stage characterized by the presence of numerous intermediate fibres. It may be concluded that the delay between reinnervation and functional recovery on the one hand and the occurrence of type grouping of muscle fibres on the other represents the time necessary for the reversal of the enzymatic pattern in muscle fibres being reinnervated by axons different from the original ones. The transitional stage observed between the normal pattern and the type grouping is probably the morphological expression of this evolution.

Changes in motor innervation and histochemical pattern of muscle fibers in some congenital myopathies

Changes in motor innervation were compared with histologic and histochemical pattern of muscle fibers in three biopsies of central core disease, four biopsies of nemaline myopathy, one biopsy of myotubular myopathy, and three biopsies of mitochondrial myopathy. Evidence of collateral reinnervation was obtained only in one biopsy from central core disease. In other biopsies, no structural or ultrastructural abnormality of axis cylinders, myelin, or myoneural junction suggesting denervation were observed. The only relevant change found in centronuclear myopathy and to a lesser extent in nemaline myopathy was an unusual smallness and simplification of motor endings, suggesting delayed or impaired maturation. Muscle fibers strongly reactive for both adenosinetriphosphatase and nicotinamide-adenine dinucleotide diaphorase, observed in central core disease and mitochondrial myopathy, were not associated with increased terminal innervation ratio.

Familial focal loss of cross striations

SummaryTwo patients, a brother and sister, both suffering from congenital generalized muscle weakness with a progressive course are reported. Muscle biopsy revealed areas with loss of cross striations in the muscle fibers, electronmicroscopically presenting complete disorganization of the myofibrils with streaming of the Z discs and absence of mitochondria. Vesicular nuclei with prominent nucleoli were present in these areas. There was a type I fiber prodominance in both cases. The mean diameter of the type I muscle fibers in one of the cases was too small. Motor endplate alterations in this patient gave no evidence of denervation but were suggestive of a delayed development of motor nerves.ZusammenfassungEs werden zwei Patienten beschrieben, Bruder und Schwester, beide an einer kongenitalen, generalisierten, progressiven Muskelschwäche leidend. Die Muskelbiopsie zeigte Zonen mit Verlust der Querstreifung in den Muskelfasern, und bei elektronenmikroskopischer Untersuchung zeigte sich eine totale Unordnung der Myofibrillen mit Strömung der Z-Scheiben und Fehlen von Mitochondrien. In diesen Bezirken fanden sich blasige Kerne mit prominenten Nukleolen. In beiden Fällen zeigte sich ein starkes Überwiegen der Typ-I-Fasern. Der mittlere Durchmesser der Typ-I-Muskelfasern war in einem der Fälle zu gering. Veränderungen in der motorischen Endplatte in diesem Fall zeigten keine Denervierung, sondern deuteten auf eine verzögerte Entwicklung der motorischen Nerven.

MORPHOLOGICAL AND HISTOCHEMICAL CHANGES OF MOTOR UNITS IN MYASTHENIA

Neuromuscular biopsies were obtained from 45 myasthenic patients. Motor innervation was studied in all specimens by vital staining with methylene blue. Quantitative data included the proportion of elongated motor endings, and the terminal innervation ratio (TIR) of motor axons. Quantitative histochemical data, obtained on 12 biopsies, included the atrophy factors of type I and II fibers, the I/II ratio, and the proportion of fibers strongly reacting to both ATPase and NADH diaphorase (type III fibers). Statistical analysis of the data led to the following conclusions: (1) elongated motor endings, found in 26 biopsies, were not related to denervation or to the severity of the disease, and were preferentially observed in younger patients; (2) increased TIR suggesting denervation was observed in 7 biopsies, only in patients over 50 years; and (3) various histochemical changes were found, mainly numeric reduction of type II fibers, having no demonstrable relationship with the incidence of elongated motor endings. The highest TIR was observed in a biopsy containing an increased proportion of type III and intermediate muscle fibers.

Infantile spinal muscular atrophy variant with congenital fractures in a female neonate: evidence for autosomal recessive inheritance

We read with great interest the article published in this journal in 1991 by Borochowitz et al ,1 describing a new lethal syndrome consisting of infantile spinal muscular atrophy (SMA) and multiple congenital bone fractures in two sibs. Recently, another infant with a form of SMA and congenital fractures was reported by Kelly et al ,2 thus validating the suggestion of a distinct and rare form of SMA associated with congenital bone fractures. Autosomal recessive inheritance was suggested in the original report,1 but no history of consanguinity was noted in the second.2 X linked inheritance could, however, not be excluded since these three affected infants were male. Greenberg et al 3 reported four cases with infantile SMA, neonatal death, congenital joint contractures, and the presence of bone fractures in three of the four cases; these cases seem clinically to be similar to the originally reported cases,1 but the pedigree in this report was consistent with X linked recessive inheritance and the gene in this family was mapped to Xp11.3-q11.2.4 Here, we report on a female neonate with a severe, acute, lethal form of SMA and congenital bone fractures, thus excluding X linked inheritance. Furthermore, since this girl was born to first cousin parents, this suggests autosomal recessive inheritance in this rare variant of SMA type 1 with congenital fractures. The girl was born to a 35 year old, G5 P5 mother and a 41 year old father. The parents, of Moroccan origin, were consanguineous, as were the maternal grandparents. They had one healthy son and two healthy daughters, and another son who had died at the age of 3 months in Morocco. The pregnancy was not medically followed but reported by the mother as uneventful. Delivery, recorded as normal by both gynaecologist and mother, …

Orthostatic hypotension with lower brain stem glioma

A patient with long standing orthostatic hypotension with fixed pulse rate due to involvement of the medullary regulatory centres by a lower brain stem glioma is described.

Differential diagnosis of limb-girdle muscular dystrophy and spinal muscular atrophy.

Neuromuscular biopsies from 18 patients with proximal muscle weakness were classified electromyographically as myopathy (11 cases), denervation (3 cases), or inconclusive (4 cases). Myopathic changes of muscle fibers occurred In all biopsies. Small angular dark fibers were observed in nine biopsies, and small-group atrophy in four biopsies from the three above-mentioned groups. Two biopsies classified as denervation showed large-group atrophy. Terminal innervation ratio (TIR) was increased only in the three cases classified as denervation and in one inconclusive case. TIR, which is more closely correlated with electromyographic (EMG) results than are muscle fiber changes, may help differentiate spinal muscular atrophy from limb-girdle muscular dystrophy.

Toxoplasma encephalitis in a HIV patient: unusual involvement of the corpus callosum

In patients with acquired immuno-deficiency syndrome, the differential diagnosis between primary brain lymphoma and toxoplasma encephalitis is not radiologically always straightforward, especially in the presence of a solitary cerebral lesion. In this context, involvement of the corpus callosum is almost exclusively associated with primary brain lymphoma. We describe here an HIV-infected patient who presented with a single and large cerebral lesion affecting the corpus callosum, suggestive of primary brain lymphoma on MRI-scan but who nonetheless responded clinically and radiologically to an anti-toxoplasma drug trial confirming the diagnosis of toxoplasma encephalitis.