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Published on: November 19, 2012
Hippocampal sclerosis in dementia, epilepsy, and ischemic injury: differential vulnerability of hippocampal subfields
Kimmo J Hatanpaa1, Jack M Raisanen, Emily Herndon
1From the Alzheimer's Disease Center (KJH, EH, CF, CLW) and Departments of Pathology (KJH, JMR, EH, DKB, CF, CLW), and Neurology and Neurotherapeutics (AH), University of Texas Southwestern Medical Center, Dallas, Texas; and VA North Texas Health Care System, Dallas, Texas (AH).
Insights
Hippocampal sclerosis (HS) shows varied neuronal loss patterns in dementia, epilepsy, and ischemic injury. Different hippocampal subfields are affected, indicating distinct pathological mechanisms in these conditions.
Area of Science:
- Neuroscience
- Neuropathology
Background:
- Hippocampal sclerosis (HS) is characterized by severe neuronal loss in the hippocampus.
- HS is observed in frontotemporal lobar degeneration (FTLD), temporal lobe epilepsy (TLE), and hippocampal ischemic injury (H-I).
- Shared pathogenetic mechanisms may explain selective vulnerability of hippocampal subfields, like CA1, across these conditions.
Purpose of the Study:
- To determine the extent of neuronal loss in specific hippocampal subfields in HS-FTLD, HS-TLE, and H-I.
- To investigate potential differences in pathogenetic mechanisms underlying HS in these clinical contexts.
Main Methods:
- Analysis of human autopsy tissue samples from 14 cases of HS-FTLD, 35 cases of HS-TLE, and 20 cases of H-I.
- Immunohistochemistry for zinc transporter 3 was used to delineate the CA3/CA2 border.
- Quantification of neuronal loss in the subiculum, CA regions (excluding CA1), distal CA1, and proximal-middle CA1.
Main Results:
- Subiculum involvement varied significantly: 57% in HS-FTLD, 10% in H-I, and 0% in HS-TLE (p<0.0001).
- CA regions excluding CA1 were affected in 57% of HS-TLE, 30% of H-I, and 0% of HS-FTLD (p=0.0003).
- Distal CA1 was most affected in HS-FTLD (79%), while proximal-middle CA1 was primarily affected in H-I (50%) and HS-TLE (29%).
Conclusions:
- The distinct patterns of neuronal loss in hippocampal subfields support heterogeneity in the pathogenesis of hippocampal sclerosis.
- These findings suggest that different underlying mechanisms contribute to HS in FTLD, TLE, and ischemic injury.
Abstract:
Severe neuronal loss in the hippocampus, that is, hippocampal sclerosis (HS), can be seen in 3 main clinical contexts: dementia (particularly frontotemporal lobar degeneration [FTLD]), temporal lobe epilepsy (TLE), and hippocampal ischemic injury (H-I). It has been suggested that shared pathogenetic mechanisms may underlie selective vulnerability of the hippocampal subfields such as the CA1 in these conditions. We determined the extent of neuronal loss in cases of HS-FTLD (n=14), HS-TLE (n=35), and H-I (n=20). Immunohistochemistry for zinc transporter 3 was used to help define the CA3/CA2 border in the routinely processed human autopsy tissue samples. The subiculum was involved in 57% of HS-FTLD, 10% of H-I, and 0% of HS-TLE cases (p<0.0001). The CA regions other than CA1 were involved in 57% of HS-TLE, 30% of H-I, and 0% of HS-FTLD cases (p=0.0003). The distal third of CA1 was involved in 79% of HS-FTLD, 35% of H-I, and 37% of HS-TLE cases (p=0.02). The distal third of CA1 was the only area involved in 29% of HS-FTLD, 3% of HS-TLE, and 0% of H-I cases (p=0.019). The proximal-middle CA1 was the only area affected in 50% of H-I, 29% of HS-TLE, and 0% of HS-FTLD cases (p=0.004). These findings support heterogeneity in the pathogenesis of HS.
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