Page 20 - ILAE_Lectures_2015
P. 20

Chapter 4

Neuropathology of epilepsy

MARIA THOM

Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College
London
____________________________________________________________________________

The effects of seizures on the brain are complex and have to be disentangled from the effects of
any primary, underlying neurological disease process that has led to increased seizure
susceptibility. Although there is evidence to support detrimental effects of seizures on brain
histology, this is not inevitable1,2. Prolonged seizures may result in neuronal death by apoptotic
(programmed or ‘active’) or necrotic pathways, as well as gliosis and microglial activation.
Furthermore, injurious effects of seizures should be evaluated not only by histological changes,
but at the subcellular, synaptic and molecular level. Neuropathological alterations may be
adaptive and reversible while others are permanent.

POST MORTEM EXAMINATIONS IN EPILEPSY
Post mortems carried out in patients with epilepsy include both Coroner’s examinations
(particularly in unexpected and accidental deaths) and hospital post mortems, requested by the
clinician with consent of the family. Epilepsy-related deaths are those where seizures may have
directly contributed to the cause of death. In the examination of a brain from a patient with
epilepsy, the neuropathologist addresses three main questions in relation to this disease: i) can a
cause for the epilepsy be identified? ii) are secondary changes as a result of seizures present? iii)
is there any direct contribution of epilepsy to the cause of death. Regional tissue sampling is
guided by any macroscopic abnormality or from localising clinical, electrophysiological and/or
neuroimaging data. For secondary changes from seizures, regions of brain most vulnerable
include the hippocampus, neocortex, thalamus, amygdala and cerebellum.

Epilepsy-related deaths

Status epilepticus: In status epilepticus, normal inhibitory mechanisms fail and epileptic activity
becomes self-sustaining. Identified pathomechanisms include endocytosis and down-regulation
of GABAA receptors3, along with recruitment of AMPA and NMDA receptors, with an overall
pro-convulsant effect. Over a longer time course, depletion of inhibitory peptides dynorphin,
galanin, somatostatin and neuropeptide Y occurs, while pro-convulsants including substance P
increase, acting to self-sustain seizures4. Neuropathological findings reported following fatal
cases of status epilepticus (SE) include neuronal loss or injury in hippocampal CA1, CA3 and
the hilus (the dentate granule cells may be spared5), amygdala (corticomedial and basolateral
nuclei), neocortex (mid-cortical layers), the entorhinal cortex, Purkinje cell layer of the
cerebellum6, mamillary bodies7, the dorsal medial nuclei of the thalamus8 and basal ganglia5. The
neuronal damage may be predominantly unilateral in some cases8 and with histories of prolonged
hemi-convulsions cerebral hemiatrophy can eventually occur with striking unilateral laminar
necrosis of the second to fourth cortical layers9. Neuronal loss, however, is not an inevitable
consequence of status epilepticus.
   15   16   17   18   19   20   21   22   23   24   25