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Evidence that febrile convulsions may cause hippocampal sclerosis or other neuronal
damage

Human pathology: post-mortem studies. There are reports of neuronal necrosis in the brains
of children who died after prolonged ‘febrile convulsions’40. The neuronal necrosis is
described as particularly involving cerebral cortex, the hippocampi and the cerebellum41.
These authors were describing extreme cases that were far from typical of the majority of
febrile convulsions.

Retrospective study of patients with temporal lobe epilepsy. Falconer et al42 reported on the
pathological findings in the resected temporal lobes of 100 adults with refractory temporal
lobe epilepsy. About half had ‘mesial temporal sclerosis’ which varied from loss of nerve
cells in the Sommer (H1) sector of the hippocampus to wider involvement of the temporal
lobe. In 40% of the patients with mesial temporal sclerosis there was a history of ‘infantile
convulsions’, suggesting a causal relationship.

Imaging studies. Radiological studies (pneumoencephalograms and CT scans) have shown
brain swelling and then atrophy in children (some of whom were febrile) after episodes of
status epilepticus43. More recently studies using MRI scans have reported similar findings in
the hippocampus after prolonged and focal febrile seizures44,45 and after febrile status
epilepticus46.

Kuks et al47 studied 107 patients with drug resistant epilepsy using high-resolution volumetric
MRI. Of these patients 45 had focal or diffuse hippocampal volume loss and there was a
strong association between hippocampal sclerosis and a history of childhood febrile
convulsions. The authors pointed out that this association does not prove a causal relationship
and that 64% of their patients with hippocampal volume loss gave no history of febrile
convulsions, so if childhood febrile convulsions cause some cases of hippocampal sclerosis
this cannot be the only mechanism.

Scott et al48 performed diffusion-weighted magnetic resonance studies and found evidence
of early vasogenic oedema after febrile convulsions. They concluded that their findings were
most consistent with a pre-existing hippocampal abnormality predisposing to febrile
convulsions. A Finnish MR study showed that the occurrence of mesial temporal sclerosis
after prolonged febrile seizures was uncommon49. A prospective study in the United States
found that after febrile status epilepticus (lasting 30 minutes or more) 11.5% of cases had
definitely or equivocally abnormal increased T2 signal in MRI scans of the hippocampus
compared with none in the control group. A substantial number also had abnormalities in
hippocampal development. A follow-up study of this group found evidence that the
hippocampal T2 hyperintensity represents acute injury often evolving to a radiological
appearance of hippocampal sclerosis after one year50.

Studies of outcome after febrile convulsions

Deaths
Two large population-based studies found no deaths that were directly attributable to febrile
convulsions10,15. The rate partly depends on how febrile convulsions are defined  some
studies have included seizures complicating known meningitis or encephalitis. A Danish
population-based study showed that long-term mortality was not increased in children with
febrile seizures, but there seemed to be a small excess mortality during the two years after
complex febrile seizures. This finding was partly explained by pre-existing neurological
abnormalities and subsequent epilepsy. They concluded that parents should be reassured that
death after febrile seizures is very rare, even in high-risk children51.