NEO TIMM[ssquote]S STAINING IN HUMAN HIPPOCAMPI FROM TLE PATIENTS: IT IS ALWAYS ASSOCIATED WITH HIPPOCAMPAL SCLEROSIS AND PROGRESSIVELY INCREASES WITH LONGER SEIZURE DURATION
Abstract number :
3.040
Submission category :
Year :
2002
Submission ID :
101
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Gary W. Mathern, Parham Yashar, Veronique Andre. Neurosurgery, MRRC, University of California, Los Angeles, Los Angeles, CA; Northwestern University School of Medicine, Chicago, IL
RATIONALE: Hippocampal fascia dentata aberrant mossy fiber sprouting is a frequent pathological finding in human temporal lobe epilepsy patients. Previously studies have reported hippocampal sclerosis (HS) patients without mossy fiber sprouting, but this was based on dynorphin immunostaining not neo-Timm[ssquote]s staining, which is often more sensitive. It is therefore controversial whether aberrant sprouting is always associated with hippocampal sclerosis (HS) patients, and how often significant sprouting occurs in cases without sclerosis.
METHODS: Neo-Timm[ssquote]s stain and cell counts were performed on 193 surgical and 10 autopsy cases. Supragranular neo-Timm[ssquote]s staining was measured by image analysis as the gray value (GV) difference between the inner and outer molecular layer (IML-OML GV). Surgical cases were classified as cryptogenic (n=38), HS (n=116), lesion only (n=19), or dual pathology (n=20). Clinical variable included age at seizure onset, duration of seizures, etc.
RESULTS: All cases of hippocampal sclerosis (mean [plusminus] SD: 107 [plusminus] 25) demonstrated significant supragranular mossy fiber sprouting compared with autopsy cases (9.9 [plusminus] 8.3; P[lt]0.0001). Based on the IML-OML GVs, 3 ranges could be determined: GVs in the autopsy range (mean+2SD; no sprouting), GVs between autopsy and HS cases (indeterminate sprouting), and GVs in HS range (mean-2SD; significant sprouting). In cryptogenic cases, 69% were in the HS range, 24% were indeterminate, and 7% showed no sprouting. For lesions, 88% were in the HS range, 6% were indeterminate, and 6% showed no sprouting. In dual pathologies, 93% were in HS range and 7% (n=1) showed no sprouting. IML-OML GVs inversely correlated with hilar cell densities (P[lt]0.0001), and positively correlated with habitual seizure duration (P=0.002).
CONCLUSIONS: Significant supragranular mossy fiber sprouting is found in all cases of HS indicating it is an important pathological marker of epileptogenesis. In addition, severe sprouting occurs in most surgical cases with cryptogenic, lesion, or dual pathologies despite less hippocampal cell loss suggesting that synaptic reorganization is a common feature in human TLE. The increase in sprouting with longer seizure duration regardless of pathological substrate supports the notion that there is a slow progression of pathological changes in human TLE as a consequence of repeated seizures similar to previous reports from our laboratory showing progressive hippocampal cell loss.
[Supported by: NIH P01 NS02802 and NS38992.]