Severe, fetal-onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5?

We present three siblings with a precise onset of fetal seizure-like activity who had severe olivopontocerebellar hypoplasia (OPCH) and degeneration. Autopsies at 20, 27, and 37 weeks gestation showed diffuse central nervous system volume loss that was most marked for the cerebellum and brain stem structures. Neuropathological abnormalities included dysplastic, C-shaped inferior olivary nuclei, absent or immature dentate nuclei, and cell paucity more marked for the cerebellar vermis than the hemispheres. Delayed development was seen in layer 2 of the cerebral cortex and in Purkinje cells of the cerebellum. Prenatal monitoring defined a developmental window of 16-18 weeks gestation when ultrasonic assessment of cerebellar width was used for prenatal diagnosis. We discuss our findings in the context of the differential diagnosis for infantile (O)PCH and propose a classification scheme for the pontocerebellar hypoplasias. These patients represent the earliest reported with OPCH and provide unique information regarding the developmental neuropathology of this condition.

Monoamine metabolites in normal human cerebrospinal fluid and in degenerative diseases of the central nervous system.

Measurement of monoamine metabolites in cerebrospinal fluid (CSF) has been one of the few methods available to study monoamine transmitter function in the human central nervous system (CNS). It has steadily proved to be of much use in clinical research of neurological and psychiatric diseases, in which altered functions of central monoamine neurotransmitters have been identified. In this work 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were quantified in normal CSF and in patients with untreated Parkinson's disease (PD) and olivopontocerebellar atrophy (OPCA). Normal CSF was obtained from 162 patients at the time of spinal anesthesia for surgery. Reference values for monoamine metabolites were established for normal adult lumbar CSF. Up to the age of 70 years no relation of monoamine metabolite concentration with age or sex were encountered. In individuals above 70 years of age higher levels of MHPG, HVA, and 5-HIAA were present in women, while in men only higher levels of MHPG could be detected. A strong correlation between 5-HIAA and HVA concentrations were observed in all groups. PD patients exhibited normal CSF metabolite levels, but an altered 5-HIAA/HVA ratio, favoring 5-HIAA. Dominant and recessive OPCA differed essentially in HVA concentration-diminished in the first group and elevated in the last. Comparing the results obtained in PD and dominant OPCA, we suggest that the decrease of CSF HVA in the latter group might not reflect nigrostriatal degeneration as we previously thought. Possibly another factor influencing dopamine function in the CNS is involved.

[Olivopontocerebellar atrophy: clinical analysis of 100 cases].

The clinical features in 100 patients suffered from olivopontocerebellar atrophy (OPCA) and their genetic trait were studied. The diagnosis was verified in all cases with computed tomography, demonstrating the atrophy of cerebellum and brainstem, vascular, neoplastic, infectious and any other organic disorder suspected were excluded. 53 out of 100 cases were sporadic (SOPCA) and the remainder (47 cases) was familial (FOPCA). The age of onset in SOPCA group was 36.1 +/- 14.95 (M +/- SD) in average, while in FOPCA group was 28.9 +/- 11.8. It seems that the symptoms in FOPCA group develop earlier than that in SOPCA group (P less than 0.05). All 47 cases of FOPCA group belong to 36 families in which altogether 166 persons were involved. According to pedigree patterns, there were 26 families inherited as autosomal dominant trait and probably so in another 5 families. Autosomal recessive trait could be confirmed in 2 families, in which the parents of proband were consanguineous, and in 3 other families autosomal recessive trait of inheritance was highly suspected. Anticipation was demonstrated in 26 families with dominant inheritance. Generally, ataxia and weakness of legs develop as initial symptoms in 88% of cases, then followed by dysarthria, and ataxia of upper extremities. The rapid alternating test of hand was impaired in 95% of patients, however, tension tremor was revealed only in 53% of patients. A method for assessing the ataxia quantitatively was proposed, our data suggest that the quantitative alternating test in the upper extremity and the measurement of base-width in lower extremity seem to be valuable in identifying the intensity of ataxia.