Репозиторий Университета

© 2019 The Authors Background: Retigabine is an antiepileptic drug developed for the adjunctive treatment of adults with epilepsy and partial-onset seizures (POS). Following its approval in 2011, reports of ophthalmological/dermatological pigmentation/discoloration led to a restriction of the indication in 2013, and in 2017, retigabine was voluntarily withdrawn from the market because of its limited usage. Here, data are reported from four open-label extension studies focusing on long-term safety with particular emphasis on ophthalmological and dermatological events. Methods: Studies 113413 (NCT01336621), 114873 (NCT01777139), 115097 (NCT00310388), and 115098 (NCT00310375) were multicenter, open-label extension studies of retigabine (300–1200 mg/day) for the adjunctive treatment of adults with POS. Safety assessments included monitoring treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). When new safety issues were identified, protocols were amended to include additional on-treatment safety evaluations, including ophthalmological and dermatological examinations. Patients who had abnormal retinal pigmentation, unexplained vision change, pigmentation of nonretinal ocular tissue, or abnormal discoloration of skin, lips, nails, and/or mucosa at the end of the treatment phase were asked to enter a safety follow-up continuation phase comprising 6-monthly ophthalmological/dermatological assessments. Results: The safety population (patients receiving ≥ 1 dose of retigabine in the open-label phase) comprised 98, 30, 376, and 181 patients for studies 113413, 114873, 115097, and 115098, respectively. Mean (standard deviation) treatment exposure ranged from 529 (424) to 1129 (999) days. In total, 68%–96% and 4%–27% of patients across the studies experienced TEAEs and TE SAEs, respectively. There were seven on-treatment deaths and two after discontinuation. Overall, 14%–73% of patients had an on-treatment eye examination, of whom 8/53, 4/22, 17/54, and 14/36 had abnormal retinal pigmentation and 15/53, 7/22, 15/54, and 11/36 had nonretinal ocular pigmentation in studies 113413, 114873, 115097, and 115098, respectively. Four patients had confirmed acquired vitelliform maculopathy. In patients with unresolved events at discontinuation and ≥ 1 posttreatment follow-up, retinal pigmentation resolved completely in 1/3, 0/3, 0/10, and 1/7 patients and nonretinal ocular pigmentation in 1/4, 0/3, 8/10, and 4/6 patients, respectively. Overall, 12%–83% of patients had an on-treatment dermatological examination, of whom 11/58, 0/25, 23/46, and 23/37 had any-tissue discoloration, respectively. In patients with unresolved events at discontinuation and ≥ 1 posttreatment follow-up, discoloration of skin, lips, nails, and/or mucosa resolved completely in 2/3, 0/0, 7/13, and 1/11 patients, respectively. Conclusions: The safety profile of retigabine in adults with POS across four open-label studies was generally consistent with data from previous placebo-controlled studies. Discoloration of various tissues occurred in a proportion of patients treated with retigabine and resolved completely in a small number of these patients following treatment discontinuation. In addition, comprehensive eye examination identified a new adverse reaction of acquired vitelliform maculopathy in a limited number of patients.

© 2018 Elsevier B.V. Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy. Verapamil significantly increased the anticonvulsant effect of CBZ and reduced its effective dose by at least 30% (from 30 mg/kg to 20 mg/kg). Binding of carbamazepine to the poloxamer 188-coated PLGA nanoparticles enabled a 30-fold increase of its anticonvulsive effect, as compared to the free drug. The inhibition of Pgp did not influence the effectivity of carbamazepine encapsulated in nanoparticles.

© 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología Case history of a small girl outlet with epilepsy, followed by scleroderma skin damage and uveitis, neurovasculitis with white matter foci in brain on the side of skin lesion in two months, immunologic disease activity. Resistance to conventional immunosuppressive therapy forced us to initiate the treatment with tocilizumab. It was well tolerated and led to significant improvement of brain, ocular and skin manifestations.

The paper considers the necessity of using ketogenic diet and its efficacy in epilepsy. Direct and indirect effects of ketones on brain cells and molecular mechanisms of their action are discussed in detail.

© 2018 Ima-Press Publishing House. All rights reserved. With the development of current neuroimaging techniques, their role in diagnosing epilepsy is becoming more significant and that is not only in identifying the disease that plays a key role in epileptogenesis, but also in assisting a clinician in the subsequent formulation of the diagnosis, in correcting drug therapy, and, in some cases, in addressing the issue of surgical treatment in the patient. The priority technique in this case is magnetic resonance imaging (MRI) that has high sensitivity and specificity in defining the location of minor and more major lesions of the brain structure and that includes a set of current sequences that can obtain important diagnostic information about the functional state of the brain. This article highlights the International League Against Epilepsy guidelines for MRI in patients with suspected epilepsy, assesses the use of and briefly characterizes both structural and functional pulse sequences that are most commonly included in the epileptological protocol. It considers major pathological processes and evaluates anatomical and functional changes in the brain structure, which play an important role in epileptogenesis.

AIM: To evaluate the efficacy and safety of zonisamide as an add-on therapy in structural focal epilepsy in children with cerebral palsy (CP). MATERIAL AND METHODS: Sixty-four patients (36 boys and 28 girls) with spastic CP and structural focal epilepsy with refractory seizures were followed up. Patients received zonisamide in a dose of 6-8.8 mg/kg/day for ≥6 months. Treatment efficacy was assessed by the reduction of seizures depending on CP form, type of epileptic seizures, combination of zonisamide with other drugs and adverse-effects. RESULTS AND CONCLUSION: A reduction of seizures by ≥50% was identified in 60.9% of children, 10.9% showed a better recovery. The best efficacy (35.9%) was demonstrated in the treatment of generalized seizures with focal onset and in the combination with levetiracetam (35.9%). Adverse effects of mild to moderate severity were noted in 26.5% of children. The treatment was discontinued in 7.8%. Therefore, zonisamide is an effective treatment for refractory structural focal epilepsy in children with CP and comorbid pathology, which reduces the frequency of seizures without severe side-effects.

© 2018 ABV-Press Publishing House. All rights reserved. Early childhood autism, or autism spectrum disorders, is an extremely heterogeneous group of conditions that share similar symptoms of dysontogenesis. Epilepsy is the most significant comorbidity in autism. The present article covers various aspects of comorbidity between epilepsy and autism, described in the literature over the last 50 years. This review aims to analyze the development of epilepsy and autism during ontogenesis and to identify causal relationships between these diseases, considering the information on the two age peaks for epilepsy onset in patients with autism.

© 2018, ABV-Press Publishing House. Attention deficit hyperactivity disorder (ADHD) is the most common cause of behavioral disorders and learning difficulties in preschool and school-age children. Patients with ADHD are often diagnosed with concomitant diseases, which creates additional diagnostic and therapeutic challenges and leads to a more significant reduction in the quality of life. ADHD is often associated with epilepsy: ADHD manifestations are more common in individuals with epilepsy, and vice versa, patients with ADHD are more likely to have epilepsy. The estimated prevalence of ADHD in children is 7-9 %, whereas in children with epilepsy, it reaches 20-50 %. Epilepsy is also one of the most common diseases in children (affecting approximately 1 % of the pediatric population), which is often aggravated by concomitant diseases, including cognitive, behavioral and emotional disorders. Various factors, such as characteristics of epileptic process and lesions in particular portions of the brain, can underlie the development of ADHD in epilepsy. Epileptiform activity and adverse effects of antiepileptic drugs can also play an important etiological role. Some antiepileptic drugs (such as barbiturates) may cause symptoms similar to those in ADHD (in this case, inattentiveness and hyperactivity shall be considered as adverse events that can be reduced or eliminated after cessation of the drug) or exacerbate ADHD symptoms in patients with these disorders. Therefore, the drugs with no negative impact on concomitant diseases or with a positive therapeutic effect for both diseases are preferable in these cases. High prevalence of the ADHD/epilepsy combination leads to a greater reduction in the quality of life, suggesting high relevance of this problem and requiring a revision of therapeutic approaches.