Contemplating stem cell therapy for epilepsy-induced neuropsychiatric symptoms

Neuropsychiatric Disease and Treatment Dovepress open access to scientific and medical research Review Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Open Access Full Text Article Contemplating stem cell therapy for epilepsy-induced neuropsychiatric symptoms This article was published in the following Dove Press journal: Neuropsychiatric Disease and Treatment 23 February 2017 Number of times this article has been viewed Gautam Rao Sherwin Mashkouri David Aum Paul Marcet Cesar V Borlongan Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA Epilepsy – a disorder of the brain and the mind Correspondence: Cesar V Borlongan Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, MDC 78, Tampa, FL 33612, USA Tel +1 813 974 3154 Fax +1 813 974 3078 Email Epilepsy is a neurologic disorder that is characterized by having two or more unprovoked recurrent seizures due to abnormal brain activity.1–3 This complex disease consists of many syndromes, diagnostic criteria, and treatment strategies.4–6 Sixty million people are affected by epilepsy worldwide.7 In the US, epilepsy affects ~2.3 million and costs the health care system $15.5 billion either directly, through medically related costs, or indirectly, through loss of productivity.8 Also, ~30% of epileptic patients have temporal lobe epilepsy (TLE) which is characterized by complex partial seizures, limbic degeneration specifically in the hippocampus, and comorbid psychiatric disorders.9–11 There are two main classifications of seizures as stated by the International League Against Epilepsy, namely, generalized seizures and focal seizures. Generalized seizures are typically bilateral, rapidly occurring, and originate at a single point. Subtypes of generalized seizures include: tonic–clonic, absence, myoclonic, clonic, tonic, and atonic. Focal seizures originate in one hemisphere and can be either localized in that one area or distributed to other areas.12 585 submit your manuscript | www.dovepress.com Neuropsychiatric Disease and Treatment 2017:13 585–596 Dovepress © 2017 Rao et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/NDT.S114786 Powered by TCPDF (www.tcpdf.org) Abstract: Epilepsy is a debilitating disease that impacts millions of people worldwide. While unprovoked seizures characterize its cardinal symptom, an important aspect of epilepsy that remains to be addressed is the neuropsychiatric component. It has been documented for millennia in paintings and literature that those with epilepsy can suffer from bouts of aggression, depression, and other psychiatric ailments. Current treatments for epilepsy include the use of antiepileptic drugs and surgical resection. Antiepileptic drugs reduce the overall firing of the brain to mitigate the rate of seizure occurrence. Surgery aims to remove a portion of the brain that is suspected to be the source of aberrant firing that leads to seizures. Both options treat the seizure-generating neurological aspect of epilepsy, but fail to directly address the neuropsychiatric components. A promising new treatment for epilepsy is the use of stem cells to treat both the biological and psychiatric components. Stem cell therapy has been shown efficacious in treating experimental models of neurological disorders, including Parkinson’s disease, and neuropsychiatric diseases, such as depression. Additional research is necessary to see if stem cells can treat both neurological and neuropsychiatric aspects of epilepsy. Currently, there is no animal model that recapitulates all the clinical hallmarks of epilepsy. This could be due to difficulty in characterizing the neuropsychiatric component of the disease. In advancing stem cell therapy for treating epilepsy, experimental testing of the safety and efficacy of allogeneic and autologous transplantation will require the optimization of cell dosage, delivery, and timing of transplantation in a clinically relevant model of epilepsy with both neurological and neuropsychiatric symptoms of the disease as the primary outcome measures. Keywords: epilepsy, neuropsychiatric, stem cells, autologous Dovepress Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Rao et al There are three main classifications of epilepsy diagnosis: genetic, structural/metabolic, and unknown cause. Genetic epilepsy is caused by a direct genetic defect that causes seizures as one of the primary symptoms. Structural/metabolic epilepsy is caused by a distinct structural lesion or a metabolic disease that is the root cause of seizures. Examples of structural/metabolic type include traumas such as strokes or infections that lead to seizures. Unknown cause epilepsy is not meant to be similar to idiopathic. Instead, it means that there could be a genetic component or it may be due to another disease, but the underlying cause of the seizures is unknown at the current time.12 Epilepsy also presents with cognitive and behavioral deficits that are typically seen in patients with classic neuropsychiatric disorders. These deficits include: hallucination, change in affect, delusion, apathy, changes in cognition, and delirium, to name a few.13,14 People with epilepsy also share comorbidities with neuropsychiatric disorders such as anxiety, depression, and obsessive compulsive disorder.15,16 Epilepsy has been known for millennia. From the time before Hippocrates, epilepsy and its symptoms have been attributed to extra-worldly causes, as seen in its depiction in famous paintings and novels.17,18 The current treatment options for epilepsy are pharmacologic drugs (ie, antiepileptic drugs [AEDs]) and surgery. AEDs are the primary method of treatment, and function by reducing the overall firing of the brain by inhibiting sodium and other positive ion channels or by activating gamma-Aminobutyric acid (GABA)ergic channels.19 Surgical resection of the temporal lobe is an option when AED treatment fails, and involves partial removal of the seizuregenerating brain tissue in order to mana (...truncated)