Elsevier

Epilepsy Research

Volume 26, Issue 1, December 1996, Pages 151-161
Epilepsy Research

The pathogenic and progressive features of chronic human hippocampal epilepsy

https://doi.org/10.1016/S0920-1211(96)00052-6Get rights and content

Abstract

To design useful experimental models of epilepsy, it is necessary to clearly understand the known clinical-pathologic features of the disease process. Studies of mesial temporal lobe epilepsy (MTLE) patients have identified several distinctive clinical and pathophysiologic characteristics and many of these can be analyzed in experimental models. For example, patients with typical MTLE have medical histories that often contain an initial precipitating injury (IPI), are likely to have hippocampal sclerosis in the surgical specimen, and have better seizure outcomes than patients with atypical idiopathic temporal seizures (i.e. cryptogenic). Hippocampi from children as young as age 1 year with IPI histories also demonstrate neuron damage similar to adults with hippocampal sclerosis. Compared to IPI patients without seizures (i.e. trauma, hypoxia, etc.), IPI cases with severe seizures showed younger ages at the IPI, shorter latent periods, and longer durations of habitual MTLE. Hippocampal damage is often bilateral, however, the epileptogenic side shows hippocampal sclerosis and the opposite side usually shows only mild neuron losses. Moreover, MTLE patients show declines in hippocampal neuron densities with very long histories of habitual seizures (15 to 20 years), however, the additional neuron loss adds to the template of hippocampal sclerosis and occurs in limited subfields (granule cells, CA1 and prosubiculum). Hippocampal axon and synaptic reorganization is another pathologic feature of MTLE, and involves granule cell mossy fibers and axons immunoreactive for neuropeptide Y, somatostatin, and glutamate decarboxylase (which synthesizes GABA). Finally, MTLE patients with hippocampal sclerosis show increased granule cell mRNA levels for brain derived neurotrophic factor, nerve growth factor, and neurotrophin-3 that correlate with mossy fiber sprouting or with declines in Ammon's horn neuron densities. Taken together, our data support the following concepts: (1) The pathogenesis of MTLE is associated with IPI histories that probably injure the hippocampus at some time prior to habitual seizure onsets, (2) most of the damage seems to occur with the IPI, (3) there can be additional neuron loss associated with long seizure histories, (4) another pathologic feature of MTLE is axon reorganization of surviving fascia dentata and hippocampal neurons, and (5) reorganized axon circuits probably contribute to seizure genesis or propagation.

References (56)

  • T.L. Babb

    Bilateral pathological damage in temporal lobe epilepsy

    Can. J. Neurol. Sci.

    (1991)
  • T.L. Babb et al.

    Pathological findings in epilepsy

  • T.L. Babb et al.

    Distribution of pyramidal cell density and hyperexcitability in the epileptic human hippocampus

    Epilepsia

    (1984)
  • T.L. Babb et al.

    Temporal lobe volumetric cell densities in temporal lobe epilepsy

    Epilepsia

    (1984)
  • T.L. Babb et al.

    Recurrent excitatory circuits by sprouted mossy fibers into the fascia dentata of human hippocampal epilepsy

    Epilepsia

    (1988)
  • T.L. Babb et al.

    Glutamate decarboxylase immunoreactive neurons are preserved in human epileptic hippocampus

    J. Neurosci.

    (1989)
  • T.L. Babb et al.

    Synaptic reorganization by mossy fibers in human epileptic fascia dentata

    Neurosci.

    (1991)
  • T.L. Babb et al.

    Aberrant synaptic reorganization in human epileptic hippocampus: Evidence for feedforward excitation

    Dendron

    (1992)
  • T.L. Babb et al.

    Differential upregulation of mRNA neurotrophic factors in granule cells of the human epileptic fascia dentata

    Epilepsia

    (1993)
  • E. Bratz

    Ammonshornbefunde bei epileptikern

    Arch. Psychiatr. Nervenkr.

    (1899)
  • C.J. Bruton

    The Neuropathology of Temporal Lobe Epilepsy

    (1988)
  • G. Cascino et al.

    Hippocampal mossy fiber synaptic reorganization in intractable partial epilepsy: A clinicopathologic study

    Epilepsia

    (1988)
  • F. Cendes et al.

    Atrophy of mesial structures in patients with temporal lobe epilepsy: Cause or consequence of repeated seizures?

    Ann. Neurol.

    (1993)
  • A. Connelly et al.

    Seizure and cognitive outcome after surgery: The role of contralateral temporal lobe damage as revealed by quantitative proton MRS and T2 relaxometry

    Epilepsia

    (1994)
  • M.A. Dichter et al.

    Cellular mechanisms of epilepsy: A status report

    Science

    (1987)
  • M.A. Falconer et al.

    tiology and pathogenesis of temporal lobe epilepsy

    Arch. Neurol.

    (1964)
  • J.E. Franck et al.

    Physiologic and morphologic characteristics of granule cell circuitry in human epileptic hippocampus

    Epilepsia

    (1995)
  • J.A. French et al.

    Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination

    Ann. Neurol.

    (1993)
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