Xeroderma pigmentosum with neurological abnormalities. A clinical and neuropathological study.

A clinical and neuropathological study of a case of xeroderma pigmentosum with severe neurological abnormalities was performed. The patient developed sensitivity to the sun, followed by freckles and malignant skin tumors. Some years after the onset of the cutaneous symptoms, a slowly progressive mental deterioration was noted. Subsequently, dysarthria, increased sensitivity and a tendency to cry and to be easily frightened developed together with ataxia and spasticity of the limbs. Late in the course of the disease the patient was severely disabled because of spastic tetraplegia. The clinical examination revealed generalized slowing in EEG, mixed sensory and motor neuropathy in EMG, thick skull, both cerebral cortical atrophy and ventricular dilatation in computed tomography and marked decrease in cerebrospinal homovanillic acid content. The neuropathological study showed marked loss of neurons in the basal nucleus of Meynert, the substantia nigra, the cerebellum, medulla and spinal cord. Diffuse loss of neurons was noted in the cerebral cortex and in the deep cerebral nuclei. In the nerve cells, a high amount of cytoplasmic lipofuscin was observed in some areas of CNS. The sciatic nerve showed marked loss of axons and heavy deposition of collagen around the remaining nerve fibers. The present neuropathological findings explain many of the clinical symptoms observed in xeroderma pigmentosum and show similarities with those observed in olivopontocerebellar atrophy, although the basic mechanism for the CNS damage is still unclear.

Vestibular neuronitis; a neurological and neurophysiological evaluation.

Neurological and neurophysiological findings were retrospectively reviewed in a group of 50 patients with vestibular neuronitis (VN). The onsets of VN were found to be clustered in the period from August to January. A preceding infection was reported by 36% of the patients. Neurological examinations did not reveal any other relevant signs than a spontaneous nystagmus during the acute phase. The results of routine laboratory tests and cerebrospinal fluid tests were within normal limits. EEG was recorded in 37 patients; 15 patients had a definitely abnormal EEG, with a slowing of the dominant occipital rhythm or more generalized diffuse slowing in 12 cases. 5 patients, 3 of them without slowing of the background activity, had a distinct focal disturbance of intermittent slow activity in the temporal region. In control recordings, an improvement was seen in the slowing of the background activity but not in the focal disturbances. Brainstem auditory evoked responses (BSER) were recorded in 12 patients, 5 of whom had abnormal responses. The seasonal clustering of VN onsets and the association of VN with overt infections further suggest its infectious pathogenesis. The observed EEG and BSER disturbances suggest a subclinical brainstem involvement in some cases of VN.

Familial olivopontocerebellar atrophy with macular degeneration: a separate entity among the olivopontocerebellar atrophies.

A family with hereditary, neuropathologically confirmed olivopontocerebellar atrophy (OPCA) associated with macular degeneration is described. The mode of inheritance was autosomal dominant. The first symptom was insidious, progressive visual loss caused by macular degeneration. Another early sign was slow saccades. Some years after the visual symptoms, gradually progressing cerebellar dysfunction and pyramidal signs developed. Computed tomography of the brain indicated cerebellar and pontine atrophy. Finally the patients were blind, due to a severe chorioretinal atrophy, and disabled because af motor dysfunction. The present study, together with a review of other reported families with OPCA associated with macular degeneration, suggests that this disorder is a specific and clinically recognizable subtype of OPCA.

Ambient air quality and occurrence of multiple sclerosis relapse.

Infectious viruses and bacteria can trigger multiple sclerosis (MS) exacerbations. Seasonally changing concentrations of ambient air pollutants are known to predispose to transmissible infections, to induce systemic immune responses and to enhance existing peripheral inflammation. Ambient air quality and monthly MS relapse occurrence in south-western Finland were compared by multivariate logistic regression. The odds ratio of the risk of a relapse onset was over fourfold (4.143, p < 0.001) when the concentration of inhalable particulate matter (PM(10)) was at the highest quartile. Inhalable airborne particulate matter concentrations were connected to relapse occurrence. Poor air quality may enhance the seasonal changes in MS relapse occurrence by an increased susceptibility to transmissible infections.

An expanded CAG repeat sequence in spinocerebellar ataxia type 7.

Expanded CAG repeat sequences have been identified in the coding region of genes mutated in several neurodegenerative disorders, including spinocerebellar ataxia type 1 and Machado-Joseph disease. In all disorders described to date the CAG expansion codes for an elongated polyglutamine chain. An increased polyglutamine chain size leads to a more severe disease, thus correlating with the genetic anticipation seen in repeat expansion disorders. Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant spinocerebellar ataxia with anticipation and a progressive degeneration of the cerebellar cortex. Using repeat expansion detection (RED), a method in which a thermostable ligase is used to detect repeat expansions directly from genomic DNA, we have analyzed 8 SCA7 families for the presence of CAG repeat expansions. RED products of 150-240 bp were found in all affected individuals and found to cosegregate with the disease (P < 0.000001, n = 66), indicating strongly that a CAG expansion is the cause of SCA7. On the basis of a previously established correlation between RED product sizes and actual repeat sizes in Machado-Joseph disease, we were able to estimate the average expansion size in SCA7 to be 64 CAG copies.