Familial adult myoclonus epilepsy : a clinical, neurophysiological and genetic study of a familial form of myoclonic epilepsy

[摘要] ENGLISH ABSTRACT: Progressive Myoclonic Epilepsies (PME) are characterized by progressive neurologicalimpairment with myoclonus, seizures and dementia. In contradistinction, Familial AdultMyoclonic Epilepsy (FAME) is characterized by a benign course with rare seizures andcortical tremor. Both conditions have neurophysiological features suggestive of a corticalorigin for their myoclonus.This dissertation reports on a novel form of PME. Many of those who were affected had noor minimal progression of their illness, low seizure frequency and were cognitively intact,suggestive of non-progressive disorders linked to the FAME loci.The majority of patients had features of cortical myoclonus, with generalized spike and wavedischarges on electroencephalography, enlarged evoked potentials, enhanced C reflexes,and evidence of cortical excitability with magnetic stimulation. However, there was evidenceof cerebellar dysfunction both pathologically and on imaging. With regard to similarconditions, dentatorubral pallidoluysian atrophy and Unverricht-Lundborg syndrome wereexcluded by linkage analysis. Similarly, linkage was not present for either the FAME 1 orFAME 2 loci.This syndrome is both clinically and genetically novel, and has a nosology which is difficult tocharacterize, in which the condition appears to lie on the spectrum between FAME andPME. The dissociation between the pathological and radiological findings which suggestsubcortical dysfunction, and the neurophysiological findings of cortical myoclonus is striking.Review of the literature associated with the neurophysiology of related conditions associatedwith PME and FAME suggests that:1. The assumption that generalized forms of myoclonic disorders represent multifocalforms of focal cortical discharges is an oversimplification.2. The dissociation between initial and later components of the evoked potential is lessrobust than is generally supposed, and that subcortical inputs may affect latercomponents of the evoked potential.3. In a high proportion of cases the latency from cortical spike discharge to myoclonicjerk obtained with jerk locked averaging is incompatible with a cortical origin for thespike discharge.4. The proposal that myoclonus is a form of long latency reflex and that myoclonusrepresents a reflex arising from subclinical sensory input, is unproven.

[发布机构] Stellenbosch University