Late-onset unexplained epilepsy: What are we missing?

With the aging of the US population, the incidence of epilepsy will increase, with 25 to 50% of new cases with no identifiable etiology diagnosed as late-onset unexplained epilepsy (LOUE). In the current targeted review, we discuss the possible role of cerebral small vessel ischemic disease, accumulation of amyloidß and hyperphosphorylated tau, and sleep apnea as potential pathophysiologic mechanisms explaining LOUE. We highlight the impact of these processes on cognition and avenues for diagnosis and treatment.

Non-invasive Cognitive Enhancement in Epilepsy.

Epilepsy patients frequently experience cognitive difficulties, particularly in the domains of memory, attention, and executive function. Despite the frequency of these difficulties among epilepsy patients, current strategies to treat cognitive dysfunction are limited. We performed a systematic review of controlled trials of non-invasive cognitive enhancement in epilepsy. We identified studies examining the efficacy of pharmacological agents, namely the acetylcholinesterase inhibitors donepezil and galantamine, the NMDA non-competitive antagonist memantine, and the stimulant methylphenidate, as well as non-invasive non-pharmacological transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We highlight the data currently available and the limitations of the current literature.

Neuropsychological correlates of obstructive sleep apnea severity in patients with epilepsy.

Obstructive sleep apnea affects up to 30% of patients with epilepsy. As obstructive sleep apnea represents a clinical risk factor for cognitive deficits, its occurrence in epilepsy patients may exacerbate cognitive deficits associated with this condition. However, the cognitive burden of obstructive sleep apnea in epilepsy remains poorly understood. We conducted a retrospective record review of adults with epilepsy who underwent a polysomnography and a neuropsychological assessment at Brigham and Women's Hospital. We examined the relationship between obstructive sleep apnea severity and cognitive functioning, particularly attention/executive functions, memory, and processing speed in untreated obstructive sleep apnea patients with epilepsy. Twenty patients with epilepsy and mild-to-severe obstructive sleep apnea were included in the analyses. We found significant positive correlations between the oxygen saturation levels during rapid-eye-movement sleep and attention/executive tests (p<0.05), as well as time spent with saturation levels ≤90% and executive functioning (p=0.008). Similarly, worse verbal memory performances were associated with lower oxygen levels (p=0.003). In addition, more severe respiratory events during rapid-eye-movement sleep were associated with worse performances on attention tests (p=0.03). Our findings indicate that more severe obstructive sleep apnea-related hypoxemia during sleep is associated with poorer cognitive performances on tests that assess attention/executive functions and verbal memory in patients with epilepsy. Overall, these results are consistent with the sleep apnea literature, and suggest that patients with epilepsy are also vulnerable to the effects of obstructive sleep apnea. Future prospective studies will help in determining whether treatment of obstructive sleep apnea may help improve cognitive functioning in patients with epilepsy.

Growing older with drug-resistant epilepsy: cognitive and psychosocial outcomes.

We aimed to investigate the cognitive and psychosocial outcomes of patients older than 50 with drug-resistant temporal lobe epilepsy as compared to a younger cohort. One hundred and thirty-one patients with temporal lobe epilepsy (47% age ≥ 50) who underwent comprehensive neuropsychological testing were retrospectively identified. A comparison of percentage of Z scores < - 1.5 between the older and younger cohort on Trail Making Tests A and B, Boston Naming Test, Rey Auditory Verbal Learning Test (RAVLT) delayed recall, and Rey-Osterrieth complex figure test delayed recall was performed as well as the presence of disability due to epilepsy and depression scores. Grading of white matter hyperintensities on MRI was also performed. Older patients with epilepsy were more likely to score Z < - 1.5 on the RAVLT (54.1 vs 32.8%) and were more likely to be on disability due to their seizures (23.0 vs 5.7%). A higher grade of white matter hyperintensities correlated with worse performance on Trail Making Test A, while a higher number of anti-epileptic drugs (AEDs) correlated with worse performance on Trail Making Test B regardless of age. The results of this study reveal that older patients with drug-resistant epilepsy are a vulnerable population with an impaired cognitive profile. In addition, limiting the number of AEDs and addressing markers of small vessel disease should also be prioritized by clinicians.

Recurrent Epileptic Auras As a Presenting Symptom of Alzheimer's Disease.

Seizures are a common co-morbidity during the course of Alzheimer's disease (AD) and in a subset of patients may be one of the presenting symptoms. In this case series, we highlight three patients with recurrent medically refractory epileptic auras whose work up ultimately lead to the diagnosis of AD. All three patients underwent prolonged EEG, serial neuropsychological testing, FDG-PET, cerebrospinal fluid (CSF) AD biomarkers, and MRI. CSF biomarkers were particularly helpful in two cases. These cases highlight the importance of having a high index of suspicion for AD in new onset "idiopathic" epilepsy in the elderly.