1.
Personalized medicine approaches in epilepsy.
Walker, LE, Mirza, N, Yip, VLM, Marson, AG, Pirmohamed, M
Journal of internal medicine. 2015;(2):218-234
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Abstract
Epilepsy affects 50 million persons worldwide, a third of whom continue to experience debilitating seizures despite optimum anti-epileptic drug (AED) treatment. Twelve-month remission from seizures is less likely in female patients, individuals aged 11-36 years and those with neurological insults and shorter time between first seizure and starting treatment. It has been found that the presence of multiple seizures prior to diagnosis is a risk factor for pharmacoresistance and is correlated with epilepsy type as well as intrinsic severity. The key role of neuroinflammation in the pathophysiology of resistant epilepsy is becoming clear. Our work in this area suggests that high-mobility group box 1 isoforms may be candidate biomarkers for treatment stratification and novel drug targets in epilepsy. Furthermore, transporter polymorphisms contributing to the intrinsic severity of epilepsy are providing robust neurobiological evidence on an emerging theory of drug resistance, which may also provide new insights into disease stratification. Some of the rare genetic epilepsies enable treatment stratification through testing for the causal mutation, for example SCN1A mutations in patients with Dravet's syndrome. Up to 50% of patients develop adverse reactions to AEDs which in turn affects tolerability and compliance. Immune-mediated hypersensitivity reactions to AED therapy, such as toxic epidermal necrolysis, are the most serious adverse reactions and have been associated with polymorphisms in the human leucocyte antigen (HLA) complex. Pharmacogenetic screening for HLA-B*15:02 in Asian populations can prevent carbamazepine-induced Stevens-Johnson syndrome. We have identified HLA-A*31:01 as a potential risk marker for all phenotypes of carbamazepine-induced hypersensitivity with applicability in European and other populations. In this review, we explore the currently available key stratification approaches to address the therapeutic challenges in epilepsy.
2.
Association between seizures and diabetes mellitus: a comprehensive review of literature.
Yun, C, Xuefeng, W
Current diabetes reviews. 2013;(4):350-4
Abstract
Epilepsy or seizures are often observed in patients with diabetes mellitus (DM), and an emerging association between the two diseases is more than coincidental based on recent research. Approximately 25% of patients with DM experience different types of seizures. Furthermore, diabetic patients who experienced episodes of DKA also have seizures more frequently. The precise pathogenesis of seizures in the diabetes patient remains undetermined. Currently, the leading hypotheses in the literature suggest that multiple physiological factors, such as immune abnormalities, microvascular lesions in the brain, local brain damage, metabolic factors and gene mutation, may contribute to this condition. To date, there are no international criteria for the diagnosis and treatment of this condition. Although it is commonly assumed that antiepileptic drugs are necessary, most of the partial epilepsy patients with non-ketotic diabetes are resistant to frequently used antiepileptic drugs. In contrast, partial status epilepticus can be treated by diazepam, and carbamazepine is reported to be effective to some DM patients with epilepsy. However, anti-diabetic drugs are considered to be the most important factors in the treatment of this condition. When the blood glucose levels gradually return to normal levels, patients can no longer generate seizures even when antiepileptic drugs are discontinued.
3.
Treatment of refractory convulsive status epilepticus in children: other therapies.
Wheless, JW
Seminars in pediatric neurology. 2010;(3):190-4
Abstract
Refractory convulsive status epilepticus occurs when seizures are not controlled with initial benzodiazepine therapy or a subsequent anticonvulsant drug. Typically drug-induced anesthesia is then pursued with midazolam or a barbiturate. This results in prolonged, intensive care, which requires meticulous attention to medical management to minimize complications. When seizures persist other options must be considered. These include (1) other medications, (2) surgery, (3) the ketogenic diet, (4) hypothermia, (5) inhalational anesthetic agents, and (6) immune modulating therapy. This review addresses the literature related to the use of the latter (4) treatment options. I will discuss the role of each treatment and review the evidence for it's use, along with possible side-effects.
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Antiepileptic hypersensitivity syndrome: clinicians beware and be aware.
Bessmertny, O, Pham, T
Current allergy and asthma reports. 2002;(1):34-9
Abstract
Antiepileptic hypersensitivity syndrome is a serious idiosyncratic, non-dose-related adverse reaction reported to occur with phenytoin, phenobarbital, carbamazepine, primidone, and lamotrigine. The reaction usually develops 1 to 12 weeks after initiation of therapy with one of the above agents and is recognized by the classic triad of fever, rash, and internal organ involvement. Immediate discontinuation of the suspected anticonvulsant is essential for good outcome. Patients usually are managed supportively with hydration, antihistamines, H(2)-receptor blockers, and topical corticosteroids. In severe cases, the use of systemic corticosteroids may be necessary. The use of intravenous immune globulin should be limited to severe cases where Kawasaki disease or idiopathic thrombocytopenic purpura cannot be ruled out. Education of health care professionals and patients is imperative to improving outcomes and prevention of this reaction in the future.