Hippocampal cell loss in posttraumatic human epilepsy.
OBJECTIVE
We performed this study to determine whether significant head trauma in human adults can result in hippocampal cell loss, particularly in hilar (polymorph) and CA3 neurons, similar to that observed in animal models of traumatic brain injury. We examined the incidence of hippocampal pathology and its relation to temporal neocortical pathology, neuronal reorganization, and other variables.


METHODS
Twenty-one of 200 sequential temporal lobectomies had only trauma as a risk factor for epilepsy. Tissue specimens from temporal neocortex and hippocampus were stained with glial fibrillary acidic protein (GFAP) and hematoxylin and eosin (H&E). Eleven hippocampal specimens had additional analysis of neuronal distributions by using cresyl violet and immunolabeling of a neuron-specific nuclear protein.


RESULTS
The median age at onset of trauma was 19 years, the median time between trauma and onset of seizures was 2 years, and the median epilepsy duration was 16 years. The length of the latent period was inversely related to the age at the time of trauma (r=0.75; Spearman). The neocortex showed gliosis in all specimens, with hemosiderosis (n=8) or heterotopias (n=6) in some, a distribution differing from chance (p=0.02; Fisher). Hippocampal neuronal loss was found in 94% of specimens, and all of these had cell loss in the polymorph (hilar) region of the dentate gyrus. Hilar cell loss ranged from mild, when cell loss was confined to the hilus, to severe, when cell loss extended into CA3 and CA1. Some degree of mossy fiber sprouting was found in the dentate gyrus of all 10 specimens in which it was evaluated. Granule cell dispersion (n=4) was seen only in specimens with moderate to severe neuronal loss.


CONCLUSIONS
Neocortical pathology was universally present after trauma. Neuronal loss in the hilar region was the most consistent finding in the hippocampal formation, similar to that found in the fluid-percussion model of traumatic head injury. These findings support the idea that head trauma can induce hippocampal epilepsy in humans in the absence of other known risk factors.
Swartz
Barbara E
BE
Hoag Hospital Memorial Presbyterian Epilepsy Center, Newport Beach 92658-6100, and California Comprehensive Epilepsy Program, UCLA, Los Angeles, CA, USA. BSwartz@Hoaghospital.org
Houser
Carolyn R
CR
Tomiyasu
Uwami
U
Walsh
Gregory O
GO
DeSalles
Antonio
A
Rich
J Ronald
JR
Delgado-Escueta
Antonio
A
D000328:Adult; D000367:Age Factors; D000818:Animals; D001284:Atrophy / Q000473:pathology; D002452:Cell Count; D006259:Craniocerebral Trauma / Q000150:complications; D018891:Dentate Gyrus / Q000473:pathology; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000706:statistics & numerical data; D004827:Epilepsy / Q000209:etiology; D004834:Epilepsy, Post-Traumatic / Q000175:diagnosis / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein; D005911:Gliosis / Q000473:pathology; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D019579:Neocortex / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D012307:Risk Factors; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000473:pathology; D014018:Tissue Distribution
D005904:Glial Fibrillary Acidic Protein