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.

Clofibrate-induced muscular syndrome. Report of a case with clinical, electromyographic and pathologic observations.

In this report the clinical features of a case of clofibrate-induced muscular syndrome, as well as the electromyographic, histochemical, light- and electron-microscopic findings are described. The clinical features are similar to those of previously reported cases. Electromyography was consistent with a myopathy. Histochemical profile was normal. The myopathology included breakdown of contractile material, deranged mitochondria, dilated sarcoplasmic reticulum profiles, accumulation of membrane bound dense bodies, discontinuities in sarcolemma and thickening of capillary basement membrane. Macrophages invaded severely affected fibers.

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.

The mast cells of the mammalian central nervous system. III. Ultrastructural characteristics in the adult rat brain.

The brains of young adult male and female Sprague-Dawley rats were studied with the electron microscope to determine the full ultrastructural picture of two types of perivascular granular cell. One of these, referred to here as the type I cell and described by both light and electron microscopy by several authors, including ourselves, has been reported to be a mast cell (MC) almost identical to MCs outside the CNS. The other, referred to here as the type II cell and described by many authors under almost as many names, was dealt with fully by Ibrahim in several reports and regarded by him as a type of MC. It is felt that the results warrant the conclusions that the type I cells are indeed MCs, while the type II cells are closely allied to the type I cells and probably better adapted to the function they subserve in the CNS of mammals. The similarities between the two cell types probably outnumber the dissimilarities and even these have their counterparts in MCs outside the CNS. The problem of the possible confusion between the type II cells and macrophages, whether reportedly within vessel walls or in the form of modified or special 'pericytic' microglia, is discussed. It is concluded that there is no justification for regarding these cells as macrophages. Because of the similarity between the type II cells and MCs, and because of the high lipid content of the type II cells, it is suggested that these elements be called neurolipomastocytes or neurolipomastocytoid cells.

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.

Extensive pityriasis alba: a histological histochemical and ultrastructural study.

Nine patients with extensive pityriasis alba were studied using histopathological and histochemical techniques and electron microscopy. There was a reduction in the density of functional melanocytes in the affected areas without any change in their cytoplasmic activity. The melanosomes tended to be fewer and smaller, but their distribution pattern in the keratinocytes was normal. Melanosomal transfer to keratinocytes was generally not disturbed. The histology was non-specific. Hyperkeratosis and parakeratosis were not consistently present, and it seems unlikely that they played a significant role in the pathogenesis of the hypomelanosis. A variable degree of intercellular oedema and intracytoplasmic lipid droplets were present. The hypopigmentation may thus be due primarily to the reduced numbers of active melanocytes and a decrease in number and size of melanosomes in the affected skin.

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.