Epileptic Seizures and Electroencephalographic Evolution in Genetic Leukodystrophies

Abstract

The purpose of this study is to explore and compare epileptic seizures and EEG evolution in the various types of genetic leukodystrophy (GL). The authors reviewed the medical records and analyzed 69 serial EEGs in 27 patients with GLs: 13 with late infantile metachromatic leukodystrophy, one with juvenile metachromatic leukodystrophy, one with globoid cell leukodystrophy, six with X-linked childhood adrenoleukodystrophy, one with neonatal adrenoleukodystrophy, four with classic Pelizaeus-Merzbacher disease (PMD), and 1 with connatal Pelizaeus-Merzbacher disease. The diagnoses were made by biochemical and molecular studies. Two or more EEG studies with both awake and sleep traces were recorded during the varying clinical stages for each patient. At the beginning of the GLs, the EEGs were normal or showed mild slowing of background activity. Clinical seizures, mainly of focal origin, with progressive slowing and paroxysmal discharges on EEGs, usually appeared during the later stages of metachromatic leukodystrophy, X-linked childhood adrenoleukodystrophy, and classic Pelizaeus-Merzbacher disease. However, intractable seizures, mainly generalized in nature, and more severe slowing and abundant paroxysmal discharges on EEGs, with commensurate neurologic deterioration, were observed during the earlier course of globoid cell leukodystrophy, neonatal adrenoleukodystrophy, and connatal Pelizaeus-Merzbacher disease. These results indicate that GLs involve not only white matter, but gray matter as well. In all types of GL, there is good correlation between the severity of EEG changes, the severity of the diseases, and the clinical state of the patient.

Lamin B1 mediates cell-autonomous neuropathology in a leukodystrophy mouse model

“…Recent studies report epilepsy in some patients with myelin diseases, including MS and inherited leukodystrophies such as PMD (22,23). Murine models of some leukodystrophies exhibit epilepsy (24).…”

“…One explanation may be that these are rare diseases with a general lack of EEG data in affected individuals. A more careful search for electrographic abnormalities is leading to an increase awareness of seizures in some leukodystrophies (22,29). Among inherited leukodystrophies in children, 49% were noted to have epilepsy (30).…”

A Novel Catastrophic Presentation of X-Linked Adrenoleukodystrophy

“…Seizures are known to affect patients with X-ALD, typically occurring 2-4 years after onset of other neurological symptoms (Wang et al 2001). In a retrospective chart review of 485 boys, Stephenson et al (2000) noted that 9% (n ¼ 45) had an acute presentation of adrenal crisis, seizures, or encephalopathy.…”

Genetic and Physiological Evidence That Oligodendrocyte Gap Junctions Contribute to Spatial Buffering of Potassium Released during Neuronal Activity

“…A:O and reflexive coupling may also be important in pathological states, because proper K ϩ and water homeostasis affect epileptogenesis (Dudek et al, 1998;Hinterkeuser et al, 2000;Steinhauser and Seifert, 2002;Amiry-Moghaddam et al, 2003;Eid et al, 2005). Perhaps diminished K ϩ buffering contributes to the seizures that are seen in human patients and mouse models in which oligodendrocyte function is compromised, including those lacking connexin genes (Sidman et al, 1964(Sidman et al, , 1985Young et al, 1989;Wang et al, 2001;Eriksson et al, 2002;Menichella et al, 2003;Odermatt et al, 2003;Uhlenberg et al, 2004). We propose that oligodendrocytes are part of the network of cells that redistribute extracellular K ϩ generated during activity and could serve as a novel therapeutic target for diseases related to excessive excitability.…”