The relationship between hippocampal cell loss and mossy fiber sprouting (MFS), and the occurrence of spontaneous seizures (epilepsy) following early-life status epilepticus was investigated in laboratory studies at the Division of Neurology, Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA. Status epilepticus (SE) was induced in rat pups using lithium-pilocarpine injections on day 20 of postnatal development. The animals were examined in adulthood (>90 days postnatally) for the occurrence of spontaneous seizures and histological changes in the hippocampus. Of 18 animals monitored, 12 (67%) developed spontaneous seizures in adulthood, 45.2 +/- 9 days after induction of SE. Seizures consisted of running, facial clonus, head bobbing, and tail stiffening lasting 8 to 20 seconds. Some had generalized tonic-clonic seizures associated with handling. EEG correlates began in the hippocampus and spread to the frontal cortex. No intericatal epileptiform discharges or handling-induced seizures occurred in the nonepileptic pilocarpine-treated animals. Of 9 animals with spontaneous seizures studied histologically using light microscopy and Timm’s staining, only 3 (33%) had MFS and hippocampal cell loss in the dentate nucleus. Most epileptic rats and rats that did not develop spontaneous seizures showed no evidence of hippocampal structural damage. [1]

COMMENT. Laboratory studies in developing rats are a well-established method for the elucidation of seizures and their EEG, histological, and clinical correlates. Dr Brooks-Kayal and her associates have demonstrated that the hippocampal structural changes that follow early-life status epilepticus induced by chemical methods are not necessary prerequisites for later development of epilepsy. The extension of these studies to effects of early-life experimental febrile seizures induced by artificial fever on later development of hippocampal pathology and epilepsy would be of interest. [2, 3]

Febrile convulsions, hippocampal sclerosis and temporal lobe epilepsy. Complex febrile seizures in infancy or early childhood are antecedents of mesial temporal lobe sclerosis (TLS) and temporal lobe epilepsy (TLE) (Falconer, 1974). TLE is expected in 7.5% of patients following infantile febrile SE when followed for 5 to 21 years [4]. The association between febrile seizures and TLS is controversial. No association was found, even with prolonged febrile seizures, in a long-term follow-up study at University of Oulu, Finland [5]. In 24 patients with prolonged FS and 32 with simple FS, MRI volumetry of amygdala and hippocampus showed no evidence of TLS.

In a study of 292 patients with temporal lobe epilepsy associated with hippocampal sclerosis (HS), 47% had a history of FC. In those with right-sided HS, FC had occurred in 59.6%, whereas in patients with left HS, a history of FC was found in 37.5% (p=0.0002). FC risk factors may have an affinity to the right hemisphere. [6]

The pathological basis of temporal lobe epilepsy (TLE) was studied in 22 children undergoing temporal lobectomy for refractory seizures at Hopital Ste-Justine, Universite de Montreal, Canada [7]. Significant antecedents, including complex febrile seizures, meningitis, encephalitis, and trauma, occurred in 10 (45%) patients. Mesial temporal sclerosis occurred in 12 of 15 with available hippocampal tissue, and cortical dysplasia of the temporal neocortex was found in 14 of 22 patients. These findings coexisted in 7 children. The high incidence of dual pathology may explain the early age of seizure onset.