Early decrease in intermediate monocytes in peripheral blood is characteristic of multiple system atrophy-cerebellar type.

To identify biomarkers for multiple system atrophy-cerebellar type (MSA-C), we used flow cytometry to measure surface marker expression of peripheral blood monocytes from patients with MSA-C or hereditary spinocerebellar degeneration (hSCD) and from healthy controls (HCs). The percentage of intermediate monocytes was significantly lower in MSA-C patients than in hSCD patients and HCs and showed significant positive correlations with disease duration and unified MSA rating scale scores. The percentage of CD62L+ intermediate monocytes was significantly lower in MSA-C patients than in hSCD patients and HCs. Early decrease of peripheral blood intermediate monocytes is characteristic of MSA-C and is a biomarker.

Familial infantile olivopontocerebellar atrophy.

Infantile olivopontocerebellar atrophies are rare progressive, fatal, neurologic conditions characterized pathologically by loss of neurons and gliosis in the cerebellum, pons, and inferior olivary nuclei in early life. The clinical and pathologic features of 2 brothers who presented in early infancy with failure to thrive and neurologic deterioration leading to death by the age of 5 months are reported. Magnetic resonance imaging of the brain of Patient 1 disclosed progressive pontocerebellar atrophy. Both siblings had identical patterns of neuronal loss consistent with olivopontocerebellar atrophy at postmortem examination. Serum biochemical abnormalities of low thyroid binding globulin, hypoalbuminemia, and low cholesterol, suggestive of the carbohydrate-deficient glycoprotein syndrome, were also present in both patients.

Thiamine status in inherited degenerative ataxias.

Blood thiamine levels in ataxia patients were studied. No significant differences were found between 30 patients with Friedreich's ataxia and 29 patients with olivopontocerebellar atrophy (OPCA) compared with control subjects. Both OPCA and Friedreich's ataxia patients presented significantly lower cerebrospinal fluid thiamine levels than their controls (p less than 0.001 and p less than 0.04 respectively). These results, discussed in terms of the high degree of cerebellar atrophy on CT scans in OPCA v Friedreich's ataxia patients, seem to correlate with cerebellar thiamine turnover and content.

Hypertrophic obstructive cardiomyopathy in a neonate with the carbohydrate-deficient glycoprotein syndrome.

The carbohydrate-deficient glycoprotein (CDG) syndrome in its most severe form (neonatal olivopontocerebellar atrophy) is a life-threatening multisystem disease. We report a neonate who was referred for cardiological assessment because of respiratory distress, a murmur and episodes of desaturation. After initial spontaneous improvement he presented at 9 weeks with evidence of a severe hypertrophic obstructive cardiomyopathy (HOCM). The diagnosis of CDG syndrome was suggested by the characteristic dysmorphic features, hypotonia, visual inattention and severe failure to thrive; it was confirmed by electrophoresis of serum transferrin. HOCM can be a feature of the CDG syndrome, in addition to the (previously reported) pericardial effusions.

Olivopontocerebellar atrophy of neonatal onset and disialotransferrin developmental deficiency syndrome.

Two brothers presented with olivopontocerebellar atrophy of neonatal onset. The clinical features (failure to thrive, hypotonia, liver disease, effusions, and visual inattention) were similar to those of the four cases already reported, as were the necropsy findings of olivopontocerebellar atrophy, hepatic steatosis and fibrosis, and microcystic renal changes. The clinical similarities between this and the disialotransferrin developmental deficiency syndrome were noted. The characteristic abnormality of serum transferrin found in the latter syndrome was also found in the two cases reported here. We suggest that both syndromes are caused by the same, or related, defects in glycoprotein metabolism.

Central motor conduction and glutamate deshydrogenase: activity in olivo-ponto-cerebellar atrophy.

Central motor conduction was investigated by way of magneto-electric cortico-spinal stimulation in 6 patients with sporadic olivo-ponto-cerebellar atrophy. Two patients were found to have reduced leucocyte GDH activity. Only the 3 patients with corticospinal deficits displayed increased central conduction rates, which were predominant in the lower limbs. The duration of the disease is statistically longer in patients with corticospinal deficit compared to patients with no corticospinal deficit. In OPCA, evoked motor potentials are useful in assessing the corticospinal deficit which does not appear to be linked to reduced leucocyte GDH activity.

Changes in vitamin E concentration in red blood cells and plasma of patients with olivopontocerebellar ataxia within the Schut-Swier kindred.

Many reports have documented the importance of vitamin E for the function of the nervous system, especially of the cerebellum. Therefore, we studied the concentrations of vitamin E in the blood plasma and red blood cells of patients with a hereditary form of olivopontocerebellar ataxia. The concentrations of alpha tocopherol (the principal biologically-active form of vitamin E) in the plasma and red cells of the ataxic subjects were significantly lower than those of unaffected, close relatives as well as unrelated control subjects. Total lipids, cholesterol, triglycerides and lipoproteins in the serum of the ataxia group were all within normal range. The results suggest that this specific type of familial ataxia is associated with a rare and isolated abnormality in vitamin E and/or antioxidant metabolism. The vast majority of previous reports of lower blood concentrations or deficiency of vitamin E in children or adults were also associated with deficits in the absorption of lipids or abnormalities in serum lipids and lipoproteins.