Hypometabolism and cellular neurodegeneration in the temporal lobe are common features of both Alzheimer’s disease and epilepsy. Lam et al. hypothesise that intermittent temporal lobe dysrhythmia could account for the early fluctuations in cognition in patients with Alzheimer’s disease. In this paper, the authors report two cases of Alzheimer’s disease in which there was a high index of suspicion for occult seizure activity with no history of clinical seizures or epilepsy. Both patients were initially investigated with video EEG, which revealed infrequent epileptiform activity that was more prevalent during sleep. However, when bilateral foramen ovale electrodes were inserted, more frequent spike-and-wave activity was recorded arising from the mesial temporal lobe. In the first case, episodic confusion had led to a suspicion of subclinical seizure activity without scalp EEG evidence. With foramen ovale electrode placement, there was evidence of epileptiform activity whilst the patient was sleeping not present on the simultaneous scalp EEG. Levetiracetam was then introduced with the foramen ovale electrodes still in place subsequently revealing greatly reduced epileptiform activity and substantial clinical improvement. Similarly, foramen ovale insertion in the second patient resulted in the identification of a higher degree of subclinical seizure activity compared to scalp EEG. However, the second patient was unable to tolerate anti-epileptic therapy.
The authors present a novel way to successfully determine whether patients with Alzheimer’s disease are having subclinical seizures where standard EEG has been insufficient for diagnosis. The bilateral foramen ovale electrodes are described as minimally invasive, however, they do require general anaesthesia for insertion as well as prophylactic antibiotics whilst in situ. The study is clearly limited by its small sample size and a larger sample size would be needed to validate the findings, but it may be difficult to identify patients as a result of potential ethical problems. In contrast, it could be argued that in the context of a substantial suspicion of seizure activity, a trial of anti-epileptic medication would be warranted and the first patient’s response to Levetiracetam was clearly encouraging. There is currently no single anti-epileptic drug of choice for seizures in Alzheimer’s disease which would also require large-scale studies to support an effective, evidence-based therapy.
Lam AD et al. (2017) Nature Medicine. 23 (6): 678–680.