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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats were injected intravenously with 10 mg/kg of adriamycin (doxorubicin). All the treated animals developed severe posterior limb ataxia on days 11 and 12 following the injection. Mild ataxia of the forelimbs was noted later. The animals were killed between days 10 and 50. Light microscopy revealed changes in ganglion cells of the peripheral nervous system with sparing of neurons in the central nervous system. In the spinal, paravertebral and trigeminal ganglia, necrosis of neurons was followed by mild lymphocytic infiltration, and ultimate loss of ganglion cells, and a marked proliferation of nerve sheath cells. Electron microscopic study revealed increased numbers of neurofilaments and the presence of membrane-bound cisterns in the affected dorsal root ganglion cell bodies. It is concluded that adriamycin, an important anticancer therapeutic agent, has neurotoxic properties and that it selectively damages the ganglia of the peripheral nervous system.
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PMID:Toxic effects of adriamycin on the ganglia of the peripherial nervous system: a neuropathological study. 92 18

The ultrastructure of rectal biopsy specimens from a 60-year-old woman of unusual familial ataxia with cerebrospinal fluid abnormality was investigated. She had two male siblings similarly affected and a close consanguinity in the family. Meissner's plexus neurons, Schwann cells, fibroblasts and smooth muscle cells within the rectum contained intracytoplasmic eosinophilic inclusions (IEIs) with or without intensely eosinophilic granules. Ultrastructurally the IEIs were composed of a membrane-bound, fine granular material with or without dense cores. The IEIs resembled intracytoplasmic inclusions seen in various cells of the central nervous system from a male autopsied sibling. The clinically and morphologically similar finding in the two siblings suggests an autosomal recessive inherited metabolic disorder previously unreported.
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PMID:Ultrastructure of rectal biopsy specimens in unusual familial ataxia with cerebrospinal fluid abnormality. 196 44

An 11-year-old girl was found to have severely reduced beta-galactocerebrosidase activity as evidence of late-onset globoid cell leukodystrophy, while her mother had almost normal enzyme activity in circulating white blood cells. Clinically, the patient showed a remitting course marked by seizures, ataxia, white-matter disease on computed tomographic scan, and reduced conduction velocities of peripheral nerves. Symptoms improved somewhat around the age of 10 years. Two sural nerve biopsies, performed 6 years apart, disclosed a demyelinating neuropathy. By electron microscopy, membrane-bound vacuolar lysosomes in Schwann cells of myelinated axons, unlike the typical needlelike inclusions seen in classic infantile globoid cell leukodystrophy, were present in both specimens. Thus, clinical, morphologic, and biochemical data in this patient--and her mother--emphasize, compared with past reports on late-onset globoid cell leukodystrophy, considerable variation in the nosologic spectrum of late-onset globoid cell leukodystrophy and conspicuous differences from classic infantile globoid cell leukodystrophy.
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PMID:Late-onset globoid cell leukodystrophy: unusual ultrastructural pathology and subtotal beta-galactocerebrosidase deficiency. 217 71

As reported previously, the peculiar intracytoplasmic eosinophilic inclusion bodies (IEIBs) extensively appeared in the autopsied brain tissue from a 49-year-old man having familial ataxia with cerebrospinal fluid abnormality, and histochemically showed abundant proteins, but few lipids and carbohydrates. Ultrastructurally, many membrane-bound vacuoles derived from the distended cisterns of rough-surfaced endoplasmic reticulum (RER) appeared in the neurons. They were filled with fine granular, less dense materials. The IEIBs, shown as a homogeneous dense core, were found in some of the vacuoles. Similar vacuoles also appeared in astrocytes, oligodendrocytes, vascular pericytes, ependymal and choroidal epithelial cells. It is suggested that the vacuoles result from the accumulation of metabolic products in the distended RER cisterns of the cells in the central nervous system, presumably representing a genetically determined functional abnormality of the RER in protein synthesis and/or transport.
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PMID:Further postmortem examination of a case of familial ataxia with cerebrospinal fluid abnormality: an electron microscopic study of the intracytoplasmic eosinophilic inclusion bodies in the central nervous system. 255 8

Daily doses of 6-aminonicotinamide (3-5 mg/kg) given by ip injection produced ataxia of the hind limbs progressing to an ascending paresis/paralysis, anorexia, diarrhoea and death in male and female New Zealand White and Dutch Belted rabbits. At autopsy, caecal and gastric distention were seen and the apex of the gall bladder had necrotic foci. Light microscopic lesions included atrophy and necrosis of the white lobe of Harder's gland and atrophy of seminiferous tubules with cellular necrosis, vacuolation and the presence of multinucleated giant cells. Cytoplasmic vacuolation was observed in epithelial cells from many tissues, usually in the basal portion of the cells. Vacuolation of the epithelium of the sacculus rotundus and vermiform appendix was found within the same time frame as histiocytic hyperplasia in these organs. Spongiosis and gliosis were seen in certain parts of the central nervous system. Ultrastructural alterations in the gall bladder epithelium consisted of distention of intercellular space, mild distention of perinuclear space and coalescing, intracytoplasmic, membrane-bound vacuoles, a few of which contained membranous debris. Some alterations of 6-aminonicotinamide toxicosis were prevented by simultaneous administration of nicotinamide with 6-aminonicotinamide.
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PMID:Pathology of 6-aminonicotinamide toxicosis in the rabbit. 293 36

A 65-year-old man with Tangier disease (analphalipoproteinemia) had had a progressive sensorimotor distal neuropathy with sensory ataxia for 1 year. Muscle biopsy demonstrated excess lipid vacuoles on histochemical and electron-microscopic techniques. Sural nerve biopsy showed a marked loss of large fibers and an increase in small myelinated fibers, with presence of remyelinating fibers and clusters of regeneration; a few aspects of active demyelination and some onion-like formations were also present. Lipid accumulation chiefly affected the Schwann cells of unmyelinated fibers and, to a lesser degree, of myelinated fibers, endoneurial fibroblast, and vasa nervorum. Teased fibers showed prevalent aspects of de-/remyelination and, often in association, marked myelin wrinkling suggesting axonal atrophy. This Tangier patient differs from known cases for the presence of a distal symmetrical sensorimotor polyneuropathy (not previously reported in Tangier disease) and because of the morphological findings of de-/remyelination coexisting with aspects of axonal atrophy and previous degeneration, and of lipid accumulation within striated muscle and vasa nervorum. This latter finding contrasts with the assumption that in Tangier disease vessel walls are not a site of lipid storage: probably the vasa nervorum are different, in this respect, from other vessels, because of the intense lipid metabolism of the nervous tissue. Thus we suggest that involvement of vasa nervorum in Tangier disease may be more important than previously suspected, possibly playing a role in the causation of neuropathy.
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PMID:Tangier disease. A case with sensorimotor distal polyneuropathy and lipid accumulation in striated muscle and vasa nervorum. 299 11

A newly recognized neurologic disorder of cats is described. It is characterized clinically by an abnormal coat color and development of progressive ataxia during infancy. Breeding experiments indicate that the disease is inherited in an autosomal recessive manner. Pathologically, neurologic lesions closely resemble those described in infantile neuroaxonal dystrophy of children. The most prominent microscopic alterations were marked ballooning of nerve cell processes within specific regions of the brain stem and atrophy of the cerebellar vermis. Ultrastructural studies demonstrated that dystrophic axons contained electron-dense flocculent material, multilaminated membrane-bound osmiophilic bodies and filaments. Examination of the inner ears revealed depletion of neurons in the spiral ganglia and homogeneous eosinophilic bodies within the spiral ganglia, nerve fiber tracts and organ of Corti. The concept that the disease represents an inborn error of metabolism was supported by finding axonal dystrophy in neonates prior to development of cerebellar atrophy or recognition of clinical symptoms.
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PMID:Feline hereditary neuroaxonal dystrophy. 481

We report muscle biopsy abnormalities in four patients with a chronic cholestatic syndrome, low serum vitamin E levels, absent reflexes, mild limb weakness, ataxia, and sensory loss in arms and legs. Skeletal muscle fibers contained multiple autofluorescent inclusions that show strong acid phosphatase and esterase reactivity. By electronmicroscopy, the inclusions lying between myofibrils were membrane-bound dense bodies having characteristics of both lysosomes and lipopigment material. The material was similar to that observed in vitamin E-deficient animals and probably formed in response to disordered intracellular lipid peroxidation.
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PMID:Ultrastructural and histochemical abnormalities of skeletal muscle in patients with chronic vitamin E deficiency. 618 77

Canine neuroaxonal dystrophy, a newly recognized familial disorder in Rottweiler dogs, is characterized by progressive sensory ataxia. Two of four dogs studied clinically were autopsied and the cerebellum was mildly atrophic. Massive numbers of axonal spheroids were present in many regions of the neuraxis but were most prominent in the dorsal horn of the spinal cord and the nuclei gracilis and cuneatus. Ultrastructurally, spheroids appeared to be swellings of distal axons which were filled with accumulations of smooth membrane-bound vesicles, membranous lamellae, dense bodies, and other organelles. Neuropathological changes were similar to those identified in human neuroaxonal dystrophy.
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PMID:Canine neuroaxonal dystrophy. 684 67

We have studied four children (ages 6 to 17 years) with chronic cholestasis who developed a slowly progressive neuromuscular disease characterized by ataxia, dysmetria, areflexia, loss of vibratory sensation, and a variable ophthalmoplegia. Serum vitamin E concentrations were low in all patients prior to treatment (0.17-2.0 mg/g cholesterol, normal greater than 3 mg/g). Muscle histochemical studies showed prominent yellow autofluorescence, basophilic cytoplasmic inclusions which stain with esterase and acid phosphatase, and occasional necrotic fibers. Ultrastructural findings consisted of increased number and size of membrane-bound dense bodies (lysosomes), membranous whorls, and autophagic vacuoles. Intramuscular injections of all-rac-alpha-tocopherol (0.55-1.42 mg/kg per 24 hours based on individualized pharmacokinetic data) were required in three patients to achieve normal serum vitamin E values. High-dose (32 mg/kg per 24 hours) oral supplementation was effective in one patient. After normalization of serum vitamin E concentrations for 12 to 20 months, the neurologic disease has improved in all four patients.
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PMID:Progressive neuromuscular disease in children with chronic cholestasis and vitamin E deficiency: clinical and muscle biopsy findings and treatment with alpha-tocopherol. 695 72


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