Intractable insomnia as a major comorbidity of grand mal on awakening: Case report with diagnostic polysomnographic findings and successful treatment outcome

Purpose: We report a novel case of "grand mal on awakening" from sleep presenting with intractable insomnia associated with interictal epileptiform activity (IEA) during sleep. Case Report: A 36-year-old woman with a seizure history of grand mal on awakening since age 13 years suffered from severe, persistent insomnia despite seizure control with daytime valproic acid therapy. Bedtime hypnotic therapy with zolpidem and clonazepam was ineffective. An overnight polysomnographic (PSG) study with expanded EEG seizure montage found IEA with microarousals or full arousals from sleep, with a mean rate of IEA events of 19.0 per hour. The sleep macrostructure (the cycling and distribution of sleep stages) was disturbed by the IEA events, and the sleep efficiency was 67.2%. Bedtime valproic acid therapy, 500 mg, was rapidly effective. A follow-up PSG study documented a reduced mean rate of IED events of 5.8 per hour, and an improved sleep efficiency of 87.7%. Conclusion: Severe persistent insomnia with sleep-related IEA can occur as a major comorbidity of grand mal on awakening despite full seizure control. Although standard hypnotic therapy (benzodiazepine receptor agonist; benzodiazepine) was ineffective, bedtime monotherapy with valproic acid was promptly effective, with objectively-documented improvement. Therefore, when remitted epilepsy patients complain of persistent insomnia, clinicians should consider sleep-related IEA activity, with sleep disruption and poor sleep efficiency, in the differential diagnosis. A diagnostic PSG study with expanded EEG seizure montage should be considered.