Abstracts

Rationale: It is well known that patients with temporal lobe epilepsy may present with nocturnal generalized tonic-clonic seizures, and the temporal localization depends on further investigation.Methods: We present a family with 5 individuals in three generations where the clinical pattern consisted largely of nocturnal generalized tonic-clonic seizures, but who were then shown to have an LGI1 mutation. We wish to discuss the clinical and EEG findings in these patients, and to compare these with other families with autosomal dominant partial epilepsy with auditory features (ADPEAF) or autosomal dominant lateral temporal lobe epilepsy reported in the literature. Results: The proband is a 46-year-old female who had four nocturnal generalized tonic-clonic seizures. All occurred around 5-6 am, the first one at age 19 years. She has been seizure free since adequate compliance with carbamazepine. Her first EEG performed at 19 years showed an excess of slow waves at 2-4 Hz over both posterior regions without epileptic activity. Her second EEG at 22 years showed spikes and slow spike waves alternating over both temporal regions, mostly during drowsiness, and increased during hyperventilation. During intermittent photic stimulation, a photomyoclonic response appeared. Her 40-year-old sister had her first tonic-clonic seizure at 12 years which was generalized from the onset. All but one of her subsequent attacks occurred during sleep. Before the only seizure that occurred while awake, she felt numbness of her whole body and heard a whooshing sound suggestive of neocortical temporal lobe involvement. The third sister is 52 years old; she had her first generalized tonic-clonic seizure at 19 years. A year prior to this, she had transient symptoms of a tingling sensation associated with a whooshing noise. She later had other generalized attacks preceded by this aura. A diagnosis of neocortical or lateral temporal epilepsy, possibly ADPEAF, was suggested. Although the proband only had nocturnal generalized seizures, LGI1 sequencing was performed on the basis of the family history. A c.611delC mutation leading to a frameshift and premature termination of the protein was identified. Conclusions: Generalized nocturnal and diurnal seizures associated with interictal generalized spike-wave activity occurring in a family with ADPEAF is unusual. They may represent secondarily generalized seizures or primary generalized seizures or both. In addition, photosensitivity in the proband is unusual as well. Among the reported patients with LGI1 mutation, only a few had generalized tonic-clonic seizures and interictal generalized spike-wave and/or polyspike-wave discharges. This family illustrates that patients with ADPEAF may present with generalized seizures and generalized spike-wave epileptic discharges, and may have marked intrafamilial phenotypic variability. Intensive monitoring and attention to aura with auditory features should lead to accurate diagnosis of this genetically determined epileptic syndrome.