Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: A postmortem study

Authors

  • Barah Sinjab,

    1. Department of Clinical and Experimental Epilepsy, Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Lillian Martinian,

    1. Department of Clinical and Experimental Epilepsy, Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Sanjay M. Sisodiya,

    1. Department of Clinical and Experimental Epilepsy, Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, United Kingdom
    2. Divisions of Clinical Neurology, Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, United Kingdom
    3. Epilepsy Society, Chalfont St. Peter, Bucks, United Kingdom
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  • Maria Thom

    Corresponding author
    1. Department of Clinical and Experimental Epilepsy, Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, United Kingdom
    2. Divisions of Neuropathology, Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, United Kingdom
    • Address correspondence to Maria Thom, Department of Neuropathology, UCL, Institute of Neurology, Queen Square, London WC1N 3BG, U.K. E-mail: M.Thom@ucl.ac.uk

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Summary

Purpose

Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem (PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS.

Methods

Twenty-four epilepsy PM cases (age range 25–87 years) and eight controls (age range 38–85 years) were studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4 cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet (CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs) or field fraction staining values (GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD), mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were compared within and between cases.

Key Findings

The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in HS.

Significance

Our study demonstrates that stereotypical pathologic changes, as seen in HS, are not clearly defined in the thalamus. This may be partly explained by the heterogeneity of our PM study group. With quantitation, there is some evidence for preferential involvement of the MD, suggesting a potential role in TLE, which requires further investigation.

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