Seizure Characteristics in Early-stage AD
Abstract & Commentary
By Padmaja Kandula, MD
Assistant Professor of Neurology and Neuroscience, Comprehensive Epilepsy Center, Weill Cornell Medical College
Dr. Kandula reports no financial relationships relevant to this field of study.
Synopsis: This 5-year retrospective observational study describes the epilepsy encountered in patients with amnestic mild cognitive impairment and early Alzheimer’s disease.
Source: Vossel K, et al. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol 2013;70:1158-1166.
It has long been known that epilepsy may coexist with neurodegenerative illnesses such as Alzheimer’s disease (AD). However, the timing of either clinical or subclinical epileptic activity with regards to cognitive decline has not been well established. These authors systematically studied the clinical and neurophysiologic characteristics of patients with early AD and amnestic mild cognitive impairment (aMCI) who had epilepsy vs control patients without epilepsy.
The investigators retrospectively searched the 5-year database (2007-2012) of the Memory and Aging Center at the University of California for those patients who met criteria for aMI and probable AD based on the International Working Group research criteria for aMCI or National Institute of Neurological and Communicative Disorders and Stroke — Alzheimer’s Disease and Related Disorder Association criteria.
Among these candidates, patients with either a clinical diagnosis of epilepsy (two or more unprovoked seizures or first unprovoked seizure plus epileptiform electroencephalogram [EEG]) or subclinical epileptiform activity were then identified. Those patients with early-life onset of seizures or other possible epilepsy risk factors were excluded. Eventually, 12 cases of aMCI epilepsy, 35 cases of AD epilepsy, and seven cases of AD subclinical epileptiform activity were included in the study.
Date of onset of cognitive decline was obtained by caregiver retrospective assessment of behavioral baseline change that eventually developed into an obvious aMCI or AD feature. Seizure onset was also obtained by caregivers as first spell suggestive of later habitual seizures. The date of neurodegenerative disease diagnosis was the first visit fulfilling all research criteria for aMCI or probable AD. Cognitive function was assessed with the standard Mini-Mental State Examination. All EEGs were performed with 10-20 electrode placement. Antiepileptic drug response was assessed over a minimum of 3 months and categorized as either seizure-free, partial response (seizures reduced in severity and or frequency), neutral (no change in seizures), or paradoxical worsening (increase in seizure frequency or severity).
In those patients with aMCI and epilepsy, cognitive decline occurred 6.8 years earlier at 64.3 years vs 71.1 years in those without epilepsy. Patients with probable AD and epilepsy presented with cognitive decline 5.5 years earlier (64.8 years) vs those without epilepsy (70.3 years). Patients with AD and subclinical epileptiform activity showed an earlier cognitive decline at 58.9 years vs those without epilepsy (70.3 years).
Overall, seizure onset preceded or was simultaneous with aMCI or AD diagnosis in 83% of patients. Not surprisingly, the most common seizure type (47%) was complex partial and 55% were nonconvulsive seizures. EEG testing revealed epileptiform activity in 62% of patients with aMCI or AD. Epileptiform activity was predominantly unilateral and temporal. Of the four antiepileptic drug regiments (valproic acid, phenytoin, lamotrigine, levetiracetam), lamotrigine and levetiracetam had the best tolerability and efficacy (55% and 44% seizure free, respectively).
The findings of this study — that the incidence of seizures is independent of disease stage and can occur early or coincide with onset of cognitive decline — has potentially important clinical implications. In addition, the finding that more than half of the epilepsy cases were nonconvulsive also highlights the importance of early detection of seizures in this patient cohort. However, what remains unanswered is whether aggressive clinical treatment with an appropriate antiepileptic drug regimen can ultimately improve cognitive outcome or even disease course in this group. A clinical trial to answer that question would be important.