Epilepsy in Peroxisomal Diseases

Abstract

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.

The neurology of rhizomelic chondrodysplasia punctata

“…Our results on the occurrence of seizures are in agreement with earlier studies [16]. However, previous studies have not considered the impact of the severity of biochemical defects and specific mutations in relation to epilepsy [22,23]. We found that epilepsy occurs frequently in RCDP patients irrespective of genotype or phenotype.…”

Natural history of rhizomelic chondrodysplasia punctata

“…We obtained literature cases from reports published in English (n = 62). [Lightwood, 1931; Bateman, 1936; Maitland, 1939; Hilliard, 1943; Lund, 1943; Coughlin et al, 1950; Ford et al, 1951; Scott, 1952; Briggs et al, 1953; Fraser and Scriver, 1954; Yakovac, 1954; Cohen et al, 1956; Sheach and Middlemiss, 1956; Armaly, 1957; Phillips, 1957; Brogdon and Crow, 1958; Mosekilde, 1958; van Balen and Santens, 1968; Spranger et al, 1971; Mason and Kozlowski, 1973; Levine et al, 1974; Gilbert et al, 1976; Heselson et al, 1978; Kretzer et al, 1981; Saul and Stevenson, 1982; Connor et al, 1985; Poulos et al, 1988, 1991; Eustis et al, 1990; Gray et al, 1990, 1992; Wardinsky et al, 1990; Castillo‐Taucher et al, 1991; Lenti et al, 1991; Williams et al, 1991; Suzuki et al, 1993; Gendall et al, 1994; Agamanolis and Novak, 1995; Takahashi et al, 1997; Hertzberg et al, 1999; Powers et al, 1999; Steinberg et al, 1999; Khanna et al, 2001]. We excluded certain instances in which review suggested that the proffered diagnosis was implausible or in which documentation was insufficient to confirm that the child did, indeed, have RCP, or in those few instances where the proband likely did not have classical RCP Type I.…”

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines

“…Seizures have been observed in the neonatal period in nearly all severely affected PBD-ZSD patients [70], and have been reported in 23% of less severe patients [18]. EEGs can determine the frequency and duration of seizures and should be performed whenever changes in seizure activity are suspected.…”