Leczenie padaczki dietą: renesans starej terapii

Since its introduction in 1921, the ketogenic diet has been in continuous use for children with difficult-to-control epilepsy. After decades of relative disuse, it is now both extremely popular and well studied, with approximately two-thirds of children demonstrating significant seizure reduction after 6 months. It is being used for less intractable seizures in children as well as recently adults. Modifications that help improve tolerability include the medium chain triglyceride diet, modified Atkins diet, and low glycemic index treatment. Major side effects include acidosis, increased cholesterol, kidney stones, gastroesophageal reflux, and growth disturbance. However, these side effects are usually treatable and nowadays often even preventable. Future non-epilepsy indications such as Alzheimer disease, amyotrophic lateral sclerosis, autism, and brain tumors are under active investigation. This dietary treatment for epilepsy has undergone a rebirth. Its widespread use in Poland and Europe is a welcome additional treatment for those with drug-resistant epilepsy.Dieta ketogenna od jej opracowania w 1921 r. znalazła stałe miejsce w leczeniu lekoopornej padaczki u dzieci. Po kilku dekadach względnego zapomnienia, stała się znowu popularna i szeroko badana – u ok. 2/3 dzieci stwierdza się istotne zmniejszenie częstości napadów w ciągu 6 miesięcy leczenia. Dieta ketogenna coraz częściej jest wykorzystywana w leczeniu mniej opornych padaczek, a ostatnio także u dorosłych. Pojawiają się łatwiej tolerowane odmiany diety: dieta oparta na średniołańcuchowych trójglicerydach, zmodyfikowana dieta Atkinsa czy dieta z niskim wskaźnikiem glikemicznym. Do głównych objawów ubocznych stosowania tego typu diety należą: kwasica, hipercholesterolemia, kamica nerkowa, refluks żołądkowo-przełykowy i zaburzenia wzrostu. Powyższe objawy uboczne poddają się obecnie leczeniu, a nawet można im zapobiegać. Bardzo aktywnie bada się możliwości stosowania diety poza padaczką: w chorobie Alzheimera, stwardnieniu zanikowym bocznym, autyzmie i guzach mózgu. Leczenie padaczki dietą przeżywa swój renesans. Należy się spodziewać jej szerszego zastosowania w Polsce i Europie u chorych na lekooporną padaczkę

Dziecko z padaczką w szkole i przedszkolu

Seria pięciu publikacji „One są wśród nas” poświęcona jest chorobom przewlekłym u dzieci. Zawarte sa w niej praktyczne wskazówki jak stworzyć odpowiednie warunki, aby wszystkie dzieci mogły się uczyć, rozwijać i bawić mimo choroby. Przeznaczona jest dla rodziców, opiekunów i nauczycieli w przedszkolu i szkol

Prevention of epilepsy in humans – truth or myth? The experience from Sturge-Weber syndrome and Tuberous Sclerosis Complex

Introduction. Epilepsy is a chronic neurological disease, usually decreasing the quality of life and often resulting in other comorbidities e.g. cognitive impairment in children. Despite the recent discovery of new antiepileptic drugs, roughly one in three patients suffers from drug-resistant seizures. Therefore, the prevention of epilepsy is becoming one of the most important challenges in medicine. Is it, however, in fact possible to prevent epilepsy? Clinical reflections and implications. We present the results of preventive antiepileptic treatment in children with Sturge-Weber syndrome and Tuberous Sclerosis Complex as examples of the possible prevention of epilepsy and epilepsy-associated cognitive impairment in children

Widma spektroskopii wodorowej guzów korowych w przebiegu stwardnienia guzowatego u dzieci

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder with two gene loci located on chromosomes 9q34 (TSC1) and 16p13 (TSC2). Brain abnormalities in TSC include cortical tubers, subependymal nodules, giant cell astrocytomas, and white matter lesions. Cortical tubers present disordered focal neocortical formation. However, their biology remains to be elucidated. Recently, proton magnetic resonance spectroscopy has been clinically applied to the differential diagnosis of brain changes as a noninvasive neuroimaging tool. The purpose of this study was to investigate cortical tubers by single-voxel proton spectroscopy. Material/Methods: Twenty-four children with TSC were examined using a 1.5T scanner with a standard head coil. The group of patients consisted of 12 girls and 12 boys aged 3 weeks to 28 years (median: 8.66 years). Ten healthy children (examined for other reasons, with normal MR images) were the control group. Integrated MR/MRS examinations were performed. Proton MR spectroscopy images were obtained using single-voxel point resolved spectroscopy, the PRESS technique with TE=35 ms and TR=1500 ms. Results: Proton MR spectroscopy of cortical tubers revealed increased mI/Cr ratio (1.023 versus 0.553 in healthy children) and slightly decreased NAA/Cr (0.952 vs. 1.268) and NAA/Cho ratios (0.948 vs. 1.208) in all the spectra of TSC patients. The Cho/Cr ratio was almost the same as in the control group (1.079 vs. 1.058). Lactate peaks were present in ten cortical tubers. Conclusions: Proton spectroscopy can be useful in the examination of cortical tubers in TSC as a noninvasive method to investigate neurochemistry of the brain

Role of gadolinium-based contrast agents in neurological disorders

Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI) to help with the diagnostic and monitoring processes of many diseases, including neurological disorders. Initially, it was assumed that GBCAs carry minimal risk, are safe and well tolerated. But recent reports of GBCA-associated deposition in many body tissues have raised concerns about the broader health impacts of gadolinium exposure. The aim of this review was to summarise knowledge regarding gadolinium deposition, primarily in the brain structures, and of potential GBCA-associated toxicity. Moreover, we discuss the current recommendations on the use of GBCAs, as well as alternative contrast agents and imaging techniques

Analysis of MRI spectrum of brain abnormalities in tuberous sclerosis complex : data from one institution

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder with gene loci located on chromosomes 9q34 (TSC1) and 16p13 (TSC2). Brain is the most frequently affected organ. We retrospectively reviewed magnetic resonance features of the brain in 92 patients with tuberous sclerosis, examined in our Institute from 1997 to 2006. Material/Methods: We analyzed MR imaging of the spectrum of supra- and infratentorial brain lesions encountered in TSC. MR examinations were performed with a 1.5 T scanner. The basic imaging protocol included axial SE T1WI, FSE PD, T2WI, FSE FLAIR images, sagittal T1,T2WI and coronal FLAIR images. Axial T1-WI contrast-enhanced images were obtained in each patient. Results: Cortical tubers were found in 89 of the 92 patients (96.74%) and they have been located in frontal and parietal cerebral lobes predominantly. Cerebellar tubers were found in 12/92 (13.04%), cerebral white matter lesions in 34/92 patients (36.96%), subependymal nodules in 80/92 patients (86.96%) and subependymal giant cell astrocytomas in 11/92 of our patients (11.96%). Partial agenesis of corpus callosum, cortical dysplasia, cerebellar atrophy, intracranial arterial aneurysm, enlargement of ventricles and venous malformation were rare associated findings. Administration of gadolinium was useful in detecting and delineation subependymal giant cell astrocytomas - SGCAs. Conclusions: Our study presents a wide range of MR signs and variance of the cerebral manifestations with TSC patients

Effects of adjunctive eslicarbazepine acetate on neurocognitive functioning in children with refractory focal-onset seizures.

Abstract Purpose This was a phase-II, randomized, double-blind (DB), placebo-controlled study aimed to evaluate neurocognitive effects of eslicarbazepine acetate (ESL) as adjunctive therapy in pediatric patients with refractory focal-onset seizures (FOS). Methods Children (6–16 years old) with FOS were randomized (2:1) to ESL or placebo. Treatment started at 10 mg/kg/day, was up-titrated up to 30 mg/kg/day (target dose), and maintained for 8 weeks, followed by one-year open-label follow-up. The primary endpoint was change from baseline to the end of maintenance period in the composite Power of Attention assessed with the Cognitive Drug Research (CDR) system. Behavioral and emotional functioning and quality of life (QOL), secondary endpoints, were assessed with Child Health Questionnaire-Parent Form 50 (CHQ-PF50), Child Behavior Checklist (CBCL), and Raven's Standard Progressive Matrices (SPM). Efficacy was evaluated through changes in standardized seizure frequency (SF), responder rate, and proportion of seizure-free patients. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs). Results One hundred and twenty-three patients were randomized. A noninferiority analysis failed to reject the null hypothesis that the change from baseline in the Power of Attention score in the ESL group was at least 121 ms inferior to the placebo group for all age groups. The CDR scores showed no differences between placebo and ESL in Power of Attention (1868.0 vs 1759.5), Continuity of Attention (1.136 vs − 1.786), Quality of Working Memory (− 0.023 vs − 0.024), and Speed of Memory (− 263.4 vs − 249.6). Nonsignificant differences between placebo and ESL were seen for CHQ-PF50, CBCL scores, and Raven's SPM. Episodic Memory Index showed significant negative effect on ESL. Efficacy results favored the ESL group (SF least square [LS] means 1.98 vs 4.29). The TEAEs had a similar incidence between treatment groups (41.0% vs 47.5%). Conclusions Overall ESL did not produce statistically significant effects on neurocognitive and behavioral functioning in patients with epilepsy aged 6 to 16 years. Additionally, ESL was effective in reducing seizure frequency and was well-tolerated

Long-term use of Everolimus in patients with Tuberous Sclerosis Complex: final results from the EXIST-1 study

BACKGROUND: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs) and other manifestations of tuberous sclerosis complex (TSC). However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828). Methods and FINDINGS: EXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m 2 /day) titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point) was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years) who received ≥1 dose of everolimus (median duration, 47.1 months), 57.7% (95% confidence interval [CI], 47.9-67.0) achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2%) achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs) was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence) suspected to be treatment-related were stomatitis (43.2%) and mouth ulceration (32.4%). CONCLUSIONS: Everolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a significant proportion of patients. Trial Registration ClinicalTrials.gov NCT0078982

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for the routinely used magnetic resonance imaging protocol in patients with multiple sclerosis

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis (MS) that is essential for the detection and follow-up of the disease. The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of the recommendations for examinations routinely conducted in magnetic resonance imaging departments in patients with MS, which include new data and practical comments for electroradiology technicians and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics that are necessary to establish a diagnosis as well as monitor patients with MS, which directly translates into significant clinical decisions. MS is a chronic idiopathic inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in the CNS destruction process disseminated in time and space. MRI detects focal lesions in the white and grey matter with high sensitivity (with significantly less specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume and white matter volume as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in magnetic resonance techniques, as well as the abilities of postprocessing the obtained data, has become the basis for the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MRI is unquestionably the best diagnostic tool used to follow up the course of the disease and to treat patients with MS. However, to diagnose and follow up the patients with MS on the basis of MRI in accordance with the latest standards, an MRI study must meet certain quality criteria, which are the subject of this paper

Can we prevent epilepsy? Yes, we can!

Epilepsy appears in 1% of global population and despite a progress in medicine still around 30% of patients have drug-resistant epilepsy. In recent years increasing attention is paid to possibility of epilepsy prevention. Candidate groups for such treatment are eagerly looked for. One of them is tuberous sclerosis complex (TSC)