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These results suggest that disturbed placental circulation underlies the development of PVL in the majority of cases with prenatal and peripartum brain injury. In chorioamnionitis cases, certain additional factors were suggested in the genesis of PVL. Thus, placental examination is essential for elucidating the pathophysiologic changes leading to PVL in the perinatal process.

The terminal stage of B cell differentiation culminates in the formation of plasma cells (PC), which secrete large quantities of Igs. Despite recent progress in understanding the molecular aspect of PC differentiation and maintenance, the requirement for the synthesis of secretory Igs as a contributing factor has not been explored. To address this issue, we generated activation-induced cytidine deaminase (AID)/secretory μ-chain (μs) double-knockout mice, in which a normally diverse repertoire of B cell receptors is retained, yet B cells are unable to synthesize secretory Igs. These mice possess polyclonal B cells but have no serum Igs. Following immunization in vivo, PCs, identified by CD138 expression and loss of the B220 marker, were starkly reduced in number in spleen and bone marrow of AID−/−μs−/− agammaglobulinemic mice compared with wild-type mice. Upon mitogenic stimulation in vitro, AID−/−μs−/− B cells differentiated into plasmablasts to some extent, but showed reduced survival compared with wild-type B cells. We found no evidence that this reduced survival was attributable to accumulation of membrane IgM. Our results indicate that the synthesis of secretory Igs is a requirement for maintenance of B220−CD138+ PCs.

Summary:Purpose: To clarify the electroclinical manifestation of epileptic seizures and the evolution of epilepsy in patients with peroxisomal diseases.Methods: Retrospective review of the medical records and EEGs of 14 patients with peroxisomal diseases: seven with Zellweger syndrome (ZS), two with neonatal adrenoleukodystrophy (NALD), two with acyl-CoA oxidase deficiency (AOXD), two with bifunctional enzyme deficiency (BFED), and one with rhizomelic chondrodysplasia punctata (RCDP). The diagnoses were made by biochemical analysis and pathological examinations in our laboratory.Results: Patients manifested serious neurologic deficits in the neonatal period or in early or late infancy. Patients with ZS or AOXD had partial motor seizures originating in the arms or legs or corners of the mouth. Their seizures did not culminate in generalized tonic-clonic seizures and were easily controlled by antiepileptic drugs (AEDs). Interictal EEGs of the patients with ZS showed infrequent bilateral independent multifocal spikes, predominantly in the frontal motor cortex and its surrounding regions. The EEGs of patients with AOXD showed interictal fast theta activity, predominantly in the frontocentral regions. Patients with BFED also had partial motor seizures in early infancy, but the seizures were intractable, evolving in one case to myoclonic seizures. Interictal EEGs of patients with BFED showed bilateral independent multifocal spikes that evolved to bilateral diffuse high-voltage slow waves in one case and to a hypsarythmic pattern in another case as the disease progressed. Patients with NALD had intractable tonic seizures or epileptic spasms. Interictal EEGs showed high-voltage slow waves and bilateral independent multifocal spikes, evolving in one patient to a flat pattern. The patient with RCDP, whose interictal EEGs showed frequent multifocal independent spikes, did not have epileptic seizures.Conclusions: The age of epilepsy onset or the duration of survival is related to the types of seizures occurring in patients with peroxisomal diseases. Neonates or young infants usually have partial motor seizures (facial twitching or clonic convulsions of the arms or legs) of various multifocal origins. Older infants may have generalized seizures at the onset of the disease or evolutionally. Seizure intractability is usually less severe in patients with ZS or AOXD than in patients with NALD or BFED. There is no relation between the electroclinical characteristics of epilepsy and the genetic complementation groups in peroxisomal diseases.