Disease-Modification in Epilepsy by Nonpharmacological Methods

Abstract

CommentaryIn laboratory studies, environmental enrichment (EE) refers to altered housing conditions designed to enhance sensory, motor, social, and cognitive stimulation, not to mention improved animal welfare. This may include larger housing containers, enhanced novelty and complexity of toys, exercise equipment, and increased number of occupants, relative to control conditions. EE has repeatedly been demonstrated improved outcomes across many different animal models of neurological disease (1), delaying disease onset and limiting symptom severity in both genetic and acquired diseases. These improvements are likely driven by experience-dependent synaptic plasticity of neuronal circuits, which can counteract the progression of disease, although specific mechanisms are elusive and possibly disease-specific. Epilepsy is no exception, and there exists strong rationale to anticipate beneficial effects of EE (2): Early work showed that rats raised in EE conditions are protected against excitotoxic seizures and seizure-related cell death (3), and exhibit delayed epileptogenesis in the amygdala kindling model (4, 5). The recent article by Vrinda and colleagues extends this work by introducing EE to epileptic rats, and report a range of epilepsy-, behavior-, and physiologyrelated improvements.One of the primary strengths of the article by Vrinda et al. relates to the study design. In the vast majority of research looking for anti-epileptogenic or disease-modifying therapies, interventions are almost exclusively given in the immediate hours after the precipitating insult, such as status epilepticus. But without biomarkers to identify patients likely to develop epilepsy, this is not a clinically appropriate timepoint since patients only present when they are diagnosed with epilepsy, sometimes years or decades following the causal insult. A more practical and translatable approach is to randomize treatment to patients already experiencing seizures-an approach adopted by Vrinda and colleagues. Epilepsy was triggered by pilocarpine-induced status epilepticus; after 6 weeks' monitoring for spontaneous seizures, animals entered into their respective housing programs: The EE groups were introduced into enriched cages for 6 h/day for 2 weeks, while the control rats Enriched Environment Attenuates Behavioral Seizures and Depression in Chronic Temporal Lobe Epilepsy.Vrinda M, Sasidharan A, Aparna S, Srikumar BN, Kutty BM, Rao BSS. Epilepsia 2017;58: [1148][1149][1150][1151][1152][1153][1154][1155][1156][1157][1158] Temporal lobe epilepsy (TLE) is commonly associated with depression, anxiety, and cognitive impairment. Despite significant progress in our understanding of the pathophysiology of TLE, it remains the most common form of refractory epilepsy. Enriched environment (EE) has a beneficial effect in many neuropsychiatric disorders. However, the effect of EE on cognitive changes in chronic TLE has not been evaluated. Accordingly, the present study evaluated the effects of EE on chronic epilepsy-induced alterations in cognitive ...