The causes of epilepsy: Changing concepts of etiology of epilepsy over the past 150 years

Abstract

SUMMARYThis paper provides a survey of the changing concepts of the etiology of epilepsy from 1860 to 2010, focusing on the first two 50-year periods and outlining more briefly major developments in the past 50 years. Among the concepts reviewed in the first 100 years are: the division between predisposing and exciting causes, idiopathic and genuine epilepsy, organic epilepsy, the concept of ''cause'' being equivalent to ''causal mechanism,'' Russell Reynolds etiological classification, the neurological taint and theories of degeneration, the self-perpetuating nature of seizures, reflex theories of etiology, autointoxication, heredity and eugenics, epilepsy due to brain disorders, the role of EEG and of hippocampal sclerosis, psychological theories of causation, and the multifactorial view of epilepsy etiology. In the past 50 years, the major advances in studying causation in epilepsy have been: clinical biochemistry, neuroimaging, molecular genetics, studies of mechanisms of epilepsy, better statistical methodologies and classification. A number of general observations can be made: the identification of ''cause'' is not as simple as it might at first appear; progress in the study of causation has been often erratic and travelled up many cul-de-sacs; theories of causation are heavily influenced by societal influences and fashion, and is also heavily dependent on applied methodologies; the recently explored possibility that the underlying inherited mechanisms of epilepsy are shared with other neuropsychiatric conditions is in effect a reinvention of the concept of the neurological trait, and this has ethical and social implications. Considering and classifying cause in terms of causal mechanism, as was suggested by Hughlings Jackson, is an ultimate goal.

Do reflex seizures and spontaneous seizures form a continuum? – Triggering factors and possible common mechanisms

“…In reflex seizures, an identified trigger that constantly evokes seizures is thus perceived as the direct cause integrating underlying aetiology and mechanism [24]. When applying this perspective of a ''causal mechanism'' [25,26] on ictiogenesis, all seizures may be considered the result of structural and functional changes in brain networks occurring after an initial event resulting in a lowering of the threshold for synchronized activity, i.e. hyperexcitability of certain brain areas [27].…”

Oxidative Stress and Epilepsy: Literature Review

“…Progress in the field of genetics, with techniques such as the development of sequencing methods, karyotype analysis and DNA amplification methods, has produced the identification of several genes and genetic conditions which include epilepsy in their phenotype. With progress in neuropharmacological studies it is possible to identify the involvement of neurotransmitters (GABA and glutamate), as well as other alterations in membrane functions, receptors, ionic changes and alteration of neural networks that are involved in epileptogenesis [54]. …”

One hour of pilocarpine-induced status epilepticus is sufficient to develop chronic epilepsy in mice, and is associated with mossy fiber sprouting but not neuronal death

“…Several insults, such as neonatal hypoxia, febrile seizures/hyperthermia, head trauma, stroke and brain tumors can cause brain injury and the development of spontaneous seizures after a latent period [1] . However, the exact underlying mechanisms of acquired epilepsy remain unclear, which are suggested to involve neuronal death, axonal sprouting and synaptic reorganization, and ion channelopathy [2][3][4] .…”