Although the highest incidence of epilepsy occurs after 60 years old in developed countries, so far no study has deeply investigated the possible specific pathophysiological mechanisms of late onset epilepsy (LOE). LOE patients have unknown etiology (LOEU) in more than 30% of cases and recent findings showed that LOEU patients are more likely to develop cognitive dysfunction and dementia during follow-up. Growing evidences pointed to a pivotal role of neurodegeneration in the pathophysiology of LOEU and many authors hypothesized that epileptic seizures in LOEU could be a very prodromal clinical manifestation of an occult amyloid pathology. In the last 20 years, several transcranial magnetic stimulation (TMS)-EMG and TMS-EEG studies have been performed to study neurophysiological aspects of Alzheimer's Disease (AD). Similarly, TMS protocols have been widely used in patients with epilepsy, and TMS is now accepted as a safe and valuable method to assess epilepsy pathophysiology, response to treatment and prognosis. Surprisingly, so far no study has investigated the pathophysiological mechanisms of LEOU using TMS techniques. Moreover, none has investigated the presence of possible shared neurophysiological biomarkers between AD patients and LOEU patients. Such findings could be used in future to identify patients among LOEU more likely to convert to AD dementia.
Although the highest incidence of epilepsy occurs after 60 years old in developed countries (1), so far no study has deeply investigated the possible specific pathophysiological mechanisms of this subtype of epilepsy. Growing evidences point to a pivotal role of neurodegeneration in the pathophysiology of LOEU, especially regarding the amyloidogenic pathway (3). As already mentioned above, Costa et al. recently highlighted that almost 20% of patients with LOEU converted to AD dementia during follow-up, and CSF biomarker seem to be potentially useful in predicting the likelihood of developing dementia. Given the difficulties and the costs related to perform CSF analysis in all LOEU patients, it would be of pivotal importance to find out less invasive and costly biomarkers to use in this clinical setting. Our hypothesis is to investigate whether LOEU patients exhibit shared neurophysiological biomarker with AD neurodegeneration, possibly helping clinicians in early predicting an eventual cognitive impairment. Moreover, since no study has yet investigated the occurrence of an increased primary motor cortex excitability and reduced inhibition in LOEU patients (as already demonstrated in childhood/adulthood epilepsy patients), our study would be the first to investigate the neurophysiological mechanisms underpinning the occurrence of epilepsy of unknown etiology during the elderly.