The anti-seizure drugs vinpocetine and carbamazepine, but not valproic acid, reduce inflammatory IL-1beta and TNF-alpha expression in rat hippocampus

The anti-seizure drugs vinpocetine and carbamazepine, but not valproic acid, reduce inflammatory IL-1beta and TNF-alpha expression in rat hippocampus. 18.1%]. Regardless of the type of therapy, voltage-gated potassium channel-complex antibodyCpositive patients were more likely to become seizure free compared with glutamic acid decarboxylase 65 antibodyCpositive cases (12/17 vs 2/10, = 0.0183). Conclusions: In select patients, AEDs alone were effective in controlling seizures. AEDs with sodium channel blocking properties resulted in seizure freedom in a few cases. Prospective studies are needed to clarify AED selection and to elucidate their immunomodulatory properties in AE. Autoimmune epilepsy (AE) has been linked to both antineural antibodies targeting neural intracellular proteins (GAD65, ANNA-1, Ma, etc) and cell surface antigens (voltage-gated potassium channelCcomplex [VGKC-complex], NMDA receptor, AMPA, GABA-B, mGluR5, etc). AE can occasionally occur in the absence of detected neural antibodies as well.1 Valuable clinical clues for AE are subacute onset, an unusually high seizure frequency, intraindividual seizure variability or multifocality, antiepileptic drug (AEDs) resistance, personal or family history of autoimmunity, or history of recent or past neoplasia. 2 Seizures occur as an early and prominent feature in AE, and these are characteristically CDK4/6-IN-2 refractory to conventional AED therapy.1 Although intractability is a common feature in AE, some respond to AEDs, and they remain an important aspect HRMT1L3 of therapy. The role of AEDs CDK4/6-IN-2 in these patients is also relevant as even after controlling the inflammatory response, some patients remain at risk of recurrent seizures, particularly if cerebral damage occurred during the acute encephalitic phase of the illness. Some AEDs affect cellular and humoral immune responses.3,C6 For example, carbamazepine and valproate have been shown to increase the serum levels of IL-1, IL-2, IL-4, IL-6, IL-17, and tumor necrosis factorCalpha (TNF) production.4,5 At this time, no single AED stands out as superior to others in AE, and the medically refractory nature of seizures in these patients is typically emphasized. However, occasional patients do respond to AED treatment, and it is not currently known if this occurs with medications featuring particular mechanisms of action. In this study, we aimed to explore the pattern of usage and relative efficacy of AEDs in patients with AE. METHODS To identify all relevant adult cases of AE, we CDK4/6-IN-2 searched the medical record index system of the Mayo Clinic, Rochester, for the terms autoimmune encephalitis, autoimmune epilepsy, autoimmune seizure, and limbic encephalitis from January 1, 2013, through December 31, 2015. Our search resulted in 252 cases. Among these, 50 patients were identified who fulfilled the following criteria: (1) seizures as the exclusive or predominant presenting complaint and (2) an autoimmune etiology suspected on the basis of clinical presentation, inflammatory CSF, MRI characteristics suggesting inflammation, or detection of serum and/or CSF neural autoantibody7 (physique 1). Demographic, clinical (seizure semiology, course, and associated symptoms), autoimmune serology, type of AED and immunotherapy used, EEG and radiologic characteristics, and treatment outcomes were reviewed. Open in a separate window Physique 1 Flowchart showing methodology of study designAANA-1 = antineuronal nuclear antibodyC1; AED = antiepileptic drug; EMR = electronic medical record; G-ACR = ganglionic acetylcholine receptor; GAD65 = glutamic acid decarboxylase 65; NMDAR = NMDA receptor; SSA = Sj?gren’s-syndrome-related antigen A; TPO = thyroid peroxidase; VGCC = CDK4/6-IN-2 voltage-gated calcium channel; VGKC-complex = voltage-gated potassium channelCcomplex. Baseline seizure frequency was determined by reviewing the seizure frequency stated in the clinical record prior to initiation of treatment and categorized as daily ( 1 seizure per day), weekly ( 1 seizure per week but not daily), or monthly ( 1 seizure per month but not weekly). Response to AED with and without immunotherapy was determined by review of the record documenting course following treatment initiation. Statistical analysis. Data were expressed as mean, range, and SD for continuous variables, and CDK4/6-IN-2 counts (percentages) for categorical variables. We compared.