Increased fast ripple to ripple ratios correlate with reduced hippocampal volumes and neuron loss in temporal lobe epilepsy patients.
OBJECTIVE
To determine whether hippocampal sclerosis might form an anatomical substrate for pathological high-frequency oscillations in patients with temporal lobe epilepsy (TLE).


METHODS
Intracerebral wide bandwidth electroencephalogram was recorded in patients with medically intractable complex partial seizures. A computer-automated program detected interictal normal ripples (80-150 Hz) and pathologic fast ripples (FR, 151-500 Hz) from microelectrodes within hippocampus, entorhinal, and subicular cortices. Hippocampal MRI volumetric analysis and cell density measurements were correlated with rates of FR and ripple discharge.


RESULTS
In all 13 patients, higher rates of FR (p = 0.03) and ratios of FR to ripple discharges (p = 0.02) were observed in sites ipsilateral to seizure onset compared with rates within contralateral non-ictal sites. Higher ratios of FR to ripple discharge were associated with smaller ipsilateral hippocampal volumes (p = 0.02) and lower fascia dentata (FD; p = 0.02) and Ammon's horn (p = 0.0005) neuron densities. While reduced FD and Ammon's horn neuron densities correlated with higher ratios of discharges, stepwise multiple regression analysis revealed that decreased neuron densities within CA1 and prosubiculum regions most strongly predicted ratios of FR to ripples (r(2)= 0.78, p = 0.008).


CONCLUSIONS
In surgical patients with TLE, higher ratios of FR to ripple discharges are associated with histopathologic changes found in hippocampal sclerosis. These findings support the hypothesis that pathological alterations linked with hippocampal cell loss and synaptic reorganization promote FR and reduce ripple generation.
Department of Neurology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095, USA. rstaba@mednet.ucla.edu
Richard J
RJ
Staba
Leonardo
L
Frighetto
Eric J
EJ
Behnke
Gary W
GW
Mathern
Tony
T
Fields
Anatol
A
Bragin
Jennifer
J
Ogren
Itzhak
I
Fried
Charles L
CL
Wilson
Jerome
J
Engel
D001284:Atrophy / Q000473:pathology; D001927:Brain Diseases / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology; D003936:Diagnosis, Computer-Assisted; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000706:statistics & numerical data*; D018728:Entorhinal Cortex / Q000473:pathology / Q000503:physiopathology; D017029:Epilepsy, Complex Partial / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D009474:Neurons / Q000473:pathology; D012598:Sclerosis / Q000473:pathology