B- and T-cell markers in opsoclonus-myoclonus syndrome: immunophenotyping of CSF lymphocytes.

BACKGROUND: Although many lines of evidence suggest an autoimmune etiology, the pathophysiology of opsoclonus-myoclonus syndrome (OMS) remains poorly understood and no immunologic abnormalities have correlated with neurologic severity. Conventional immunotherapies often do not prevent relapse or permanent sequelae. OBJECTIVE: To test the cellular immune hypothesis of OMS in a cross-sectional study and determine if CSF lymphocyte subset analysis provides biomarkers of disease activity. METHODS: The expression of lymphocyte surface antigens was investigated in CSF and blood of 36 children with OMS and 18 control subjects, using a comprehensive panel of monoclonal antibodies to adhesion and activation proteins in combination with anti-CD3 and anti-CD45 antibodies in four-color fluorescence-activated cell sorting. RESULTS: Although most children with OMS had normal CSF cell counts, they exhibited expansion of CD19+ B-cell (up to 29%) and gammadelta T-cell (up to 26%) subsets and a lower percentage of CD4+ T-cells and CD4/CD8 ratio, which persisted even years after disease onset and conventional treatments. The percentage of activated CSF T-cells was also higher. Abnormalities correlated with neurologic severity, as scored blinded from videotapes using a 12-item motor scale, and disease duration. No significant differences were found between tumor and no-tumor groups. In children with neuroblastoma, tumor resection or cancer chemotherapy did not alter immunologic abnormalities. CONCLUSIONS: CSF B- and T-cell recruitment is linked to neurologic signs in pediatric OMS, which may relate to relapses and disease progression.

Neurosurgical correction of upper brachial plexus birth injuries.

The authors review the cases of 116 infants treated consecutively for birth-related brachial plexus injuries. Twenty-eight infants with upper brachial plexus lesions who showed no neurological improvement by 4 months of age were selected for early surgical reconstruction (at a mean age of 5 months). Neurological improvement of the affected arm was observed in more than 90% (p < 0.05) of the children examined longer than 9 months after brachial plexus reconstruction. A conservatively managed control subgroup of 44 children, first examined at less than 3 months of age, demonstrated neurological improvement by 4 months of age and continued to show improvement at 1 year of age. Early surgical reconstruction is recommended for infants with birth-related upper brachial plexus injury who show no neurological improvement by the age of 4 months.

Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy in humans, characterized electrophysiologically by decreased nerve conduction velocities (NCVs). CMT1A is associated with a large submicroscopic DNA duplication in proximal 17p. In this report we demonstrate that a patient with a cytogenetically visible duplication, dup(17)(p11.2p12), has decreased NCV. Molecular analysis demonstrated this patient was duplicated for all the DNA markers duplicated in CMT1A as well as markers both proximal and distal to the CMT1A duplication. These data support the hypothesis that the CMT1A phenotype can result from a gene dosage effect.

Opsoclonus-myoclonus with Beckwith-Wiedemann syndrome and hepatoblastoma.

The association between Beckwith-Wiedemann syndrome and hepatoblastoma is well established and relatively commonplace. The occurrence of opsoclonus-myoclonus syndrome in individuals with occult neoplasia is also well documented. However, the development of opsoclonus-myoclonus syndrome in an infant with Beckwith-Wiedemann syndrome and hepatoblastoma has not been reported previously. The list of underlying causes of opsoclonus-myoclonus syndrome should be expanded to include hepatoblastoma, particularly in any child with features suggestive of Beckwith-Wiedemann syndrome.

A syndrome of microcephaly and retinal pigmentary abnormalities without mental retardation in a family with coincidental autosomal dominant hyperreflexia.

We describe two brothers with severe microcephaly, unusual retinal pigmentary anomalies, intellectual function in the average or low average range, and a strong family history of hyperreflexia. The brothers have a previously undescribed syndrome, while the hyperreflexia appears to represent a coincidental autosomal dominant Mendelian trait, perhaps linked to the Kell blood group system.

Miller-Dieker syndrome: lissencephaly and monosomy 17p.

Miller-Dieker syndrome, which includes lissencephaly and a characteristic phenotypic appearance, has been reported to have an autosomal recessive pattern of inheritance. However, we have found abnormalities of chromosome 17 in two of three unrelated patients with this syndrome, one with a ring chromosome 17 and the other with an unbalanced translocation resulting in partial monosomy of 17p13. A review of the literature revealed five additional patients in three families, who had Miller-Dieker syndrome and an abnormality of 17p. Thus, we propose that monosomy of distal 17p may be the cause of Miller-Dieker syndrome in some patients.