Brief clinical report and review: the Marden-Walker syndrome.

We have studied a sibship with one confirmed and three probable cases of the Marden-Walker syndrome (MWS). Our patient had the major manifestations of blepharophimosis and squint; narrowly arched palate with micrognathia; small mouth and mouth-breathing; facial deformities and distortions; congenital muscle weakness with resulting scoliosis; mild pectus excavatum; camptodactylies and hip and finger joints subluxation. In addition, he had small, apparently low-set and slightly malformed auricles with a unilateral preauricular tag. However, he had no apparent renal or cardiovascular involvement. Results of CPK, EMG, and of histochemical, light microscopic, and ultrastructural studies of muscle biopsy do not suggest a primary myopathy but rather CNS related weakness/hypotonia with small muscle mass and hypoactive DTRs. This pathogenetic hypothesis is confirmed by the presence of severe mental retardation and minor brain changes suggesting cortical atrophy. In five previously reported cases there has been microcephaly. Phenotype analysis does not convince that the MWS is a true malformation syndrome, but rather hints at the possibility of a congenital metabolic dysplasia. Genetic analysis demonstrated autosomal-recessive inheritance in this and two other instances; primarily sporadic occurrence leaves open the possibility of genetic heterogeneity.

Familial spinocerebellar degeneration with corneal dystrophy.

We report on two sisters born to normal but consanguineous parents, with the unusual combination of spinocerebellar degeneration and corneal dystrophy. Their manifestations include mental subnormality, bilateral corneal opacification starting in the second year of life and leading to severe visual impairment, and slowly progressive cerebellar abnormalities with variable dorsal column and upper motor neuron involvement. A third sister had only minor spinocerebellar signs but no eye findings, and three other sibs were completely normal. Both affected sisters underwent penetrating keratoplasty and their vision improved. Histologic examination showed findings of corneal dystrophy including corneal edema, thickening of Descemet membrane, and degenerative pannus. High-resolution light and electron microscopy of muscle and sural nerve performed on both patients was abnormal. It is suggested that, in this family, the corneal dystrophy and spinocerebellar degeneration are pleiotropic manifestations of an autosomal-recessive disorder.

Augmentation of nociceptive reflexes and chronic deafferentation pain by chemical lesions of either dopaminergic terminals or midbrain dopaminergic neurons.

Neurodegenerative diseases affecting the midbrain dopaminergic system have been reported to produce spontaneous pains like in Parkinson's disease. Using various pain tests for acute (hot plate test, HPT, tail flick, TFT, paw pressure test, PPT and paw immersion test, PIT) and chronic deafferentation (autotomy, AT, following peripheral neurectomy) pains in rats, we have investigated the effects on these tests of selective chemical lesions with 6-hydroxydopamine (6-OHDA) or/and kainic acid (KA) either in the striatum or in the substantia nigra (SN) and ventral tegmental area (VTA). 6-OHDA lesions of dopaminergic terminals in the striatum decreased significantly the latencies of all nociceptive reflexes (HPT from 11.7 +/- 1.45 s to 7 +/- 1.35 s, TFT from 4.5 +/- 0.15 s to 3.2 +/- 0.16 s and PPT on the contralateral leg from 2.07 +/- 0.45 s to 1.05 +/- 0.085 s) and accelerated the time of onset (from 10.82 +/- 2.3 days to 3.1 +/- 0.52 days) and end (from 29.5 +/- 5.6 days to 5.2 +/- 1.1 days) of AT. These effects were not modified by simultaneous injection of KA and 6-OHDA in the striatum. 6-OHDA lesions in the SN-VTA produced comparable effects to those of similar injections in the striatum, while KA lesions in the SN-VTA did not produce significant changes in the latencies of nociceptive reflexes or in the AT criteria. These results suggest that the dopaminergic system plays a major role in the processing of nociceptive information in the striatum and the limbic areas.

The myopathology of Behçet's disease--a histochemical, light-, and electron-microscopic study.

The myopathology of Behçet's disease is described in 7 patients using conventional light microscopy, histochemistry, high-resolution light microscopy and electron microscopy. Two patients had clinical evidence of peripheral neuropathy: 5 patients had no clinical evidence of neuromuscular involvement. Histochemical profile of muscle in all patients was normal. Abnormalities in muscle histology using conventional light microscopy were found in only 1 patient. High-resolution light microscopy revealed abnormalities in 3 patients whereas electron microscopy revealed abnormalities in muscle of all 7 patients. The myopathology of Behçet's disease includes thickening of capillary basement membrane, excessive pleating of sarcolemma, subsarcolemmal aggregates of mitochondria and glycogen, disorganization and breakdown of myofibrils, central nucleation and the presence of a variety of cytoplasmic inclusions. No virus particles were present.

Neurogenic muscular atrophy in Behcet's disease.

A child is reported with Behcet's disease who presented with skin and joint manifestations, oral ulcers, brainstem syndrome and neurogenic muscular atrophy. The neurogenic muscular atrophy was confirmed by electrophysiologic, histologic and histochemical studies. Electron microscopy of muscle showed a vasculopathy. The possible etiology of the muscle lesions is discussed. The relevant literature on muscle and peripheral nerve involvement in Behcet's disease is reviewed. It is proposed that neuromyopathy be added to the neurological manifestations of Behcet's disease. To our knowledge, this is the first case of neurogenic atrophy reported in Behcet's disease.

Partial (localized) lipodystrophy. Report of a case with muscle and skin abnormalities.

The light and electron microscopic myopathologic and dermatopathologic features in one patient with the partial (localized) type of lipodystrophy are described. The myopathologic changes involve both the contractile elements and the intracellular organelles, especially mitochondria that show hyperplasia and structural alterations of cristae. The dermatopathologic changes consist of a reduction in subcutaneous fat, intercellular edema, and the presence of intracytoplasmic lipid droplets. This is the first report in the literature in which the myopathologic features and detailed electron microscopy of skin in this condition are described. The myopathologic features of partial lipodystrophy are compared with those of congenital generalized lipodystrophy. It is proposed that a myopathy may be one of the manifestations of partial lipodystrophy.

Nerve and muscle in steroid-induced weakness in the rabbit.

The purpose of this study was (1) to produce a cortisone induced myopathy, (2) to find out whether or not there is an associated neuropathy, and (3) if a cortisone induced neuropathy is produced, to determine its temporal relation to the myopathy. Several corticosteroid preparations were administered to rabbits, in different dosages and for different periods of time in an attempt to produce maximal effects. Decadron and cortisone acetate in doses of 0.8 mg/kg of body weight and 10 mg/kg of body weight respectively, proved most effective in producing a myopathy. Higher dosages of decadron were fatal, and hydrocortisome, 10 mg/kg of body weight, was not effective. Experimental animals receiving effective doses of decadron, cortisone acetate, and hydrocortisone lost weight, became less agile and, with continued administration of corticosteroids, became immobile. Hind limbs were affected earlier than forelimbs. The muscle lesion consisted of Z-line irregularity and streaming, vacuolation, variation in fiber size, fragmentation and phagocytosis. Cytologic alterations consisted of Z-line streaming, mitochondrial and lipid aggregates and myofilamentous disarray and disorganization. Sciatic nerve histological and cytological findings were not different from controls. They consisted of minor degrees of thickening and tortuosity of myelin sheaths which occurred in both controls and experimental animals. The electron microscopic findings in the sciatic nerve following cortisone administration have not heretofore been reported in the literature. It is concluded that cortisone myopathy is due to a primary effect of cortisone on skeletal muscle and not secondary to a peripheral nerve lesion.

Clofibrate-induced myotoxicity in rats. Temporal profile of myopathology.

In this report, the temporal sequence of myopathology during a clofibrate-induced muscular syndrome and its recovery in rats is described using histopathologic, histochemical and electron microscopic technics. Two stages of myopathology are described: an early stage characterized by myopathic features, and a later stage characterized by neurogenic features. Although muscle histology returns to normal after 1 week of discontinuing the drug, electron microscopic abnormalities persist through the second week. It is proposed that clofibrate, in addition to its myotoxic effect, may be neurotoxic.

Postganglionic cholinergic dysautonomia: report of muscle findings in 1 case.

Heretofore unreported findings in skeletal muscle in a 4th case of pure postganglionic dysautonomia are described. They consist of variation in fiber size, Z line and myofilamentous disorganization, intracytoplasmic inclusions and honeycomb formations. The most striking alterations, however, was excess lipid accumulation without concomitant mitochondrial alterations. Sural nerve histology and cytology were normal. The mechanism of lipid accumulation in skeletal muscle of patients with dysautonomia remains unexplained.