Multicenter retrospective study of patients with PCDH19-related epilepsy: The first Hungarian cohort.

OBJECTIVE: PCDH19-related epilepsy occurs predominantly in girls and is caused by pathogenic variant of the protocadherin-19 gene. The initial seizures usually develop in association with fever, begin on average at 15 months of age, and often occur in clusters. Autistic symptoms, intellectual disability, and sleep disturbance are often associated. METHODS: In our retrospective, multicenter study, we reviewed clinical data of nine children with epilepsy genetically confirmed to be associated with PCDH19. RESULTS: In the Hungarian patient population aged 0-18 years, the prevalence of PCDH19-related epilepsy was found to be lower (1/100000 live births in females) than the reported international data (4-5/100000 live births in females). Four of our nine patients had positive family history of epilepsy (cousins, sister, and mother). We assessed brain anomalies in three patients (in one patient focal cortical dysplasia and left anterior cingulate dysgenesis, and in two children right or left hippocampal sclerosis) and in another three cases incidentally identified benign alterations on brain MRI were found. The first seizure presented as a cluster in seven out of nine children. In seven out of nine cases occurred status epilepticus. Six out of nine children had autistic symptoms and only one child had normal intellectual development. Seven of our patients were seizure free with combined antiseizure medication (ASM). The most effective ASMs were levetiracetam, valproate, and clobazam. SIGNIFICANCE: The prevalence of PCDH19-related epilepsy is presumably underestimated because of the lack of widely performed molecular genetic evaluations. Molecular genetic testing including PCDH19 pathogenic variants is recommended for female patients with an onset of seizures before the age of 3 years.

Epileptiform discharges in the anterior thalamus of epilepsy patients.

Anterior thalamus (ANT) deep-brain stimulation (DBS) is an approved therapy for drug resistant epilepsy. We aimed to identify interictal epileptiform discharges (IED) in the ANT and to investigate their relationship with surface IEDs. Fifteen patients were monitored for two consecutive nights with externalized thalamic leads to analyze the intrathalamic epileptiform activities (TIED). Forty-six % of all contacts were located within the ANT. We found that all the responders had TIEDs within the ANT, while this held true only for 44% of the non-responders. The overall response rate (RR) at 1-year follow-up was 40%, while it was 44% in bilateral ANT hit patients and 45% in epileptic focus side hit. However, in case of TIEDs present in the focus side the RR reached as high as 71%. TIED activity may prove the pathophysiological connection to the seizure focus, and stimulation of this area might have a better suppressing effect on seizures.

[The quality of life of teenagers living with cerebral palsy participating in conductive education]. / A konduktív nevelésben részesülo, cerebralis paresissel élo tinédzserek életminosége.

INTRODUCTION: For people living with cerebral palsy, it is crucial to determine and monitor their quality of life because it indirectly can predict the completion of their needs and wishes, and their health-related conditions can be subjectively judged. Cerebral palsy is one of the the most common causes of childhood-onset, probably this is the reason why most quality of life studies focus on children and not on adolescents or adults. OBJECTIVES: The aims of this study were to explore the quality of life of teenagers living with cerebral palsy receiving conductive education provided by the Peto András Faculty of Semmelweis University, and to map the differences and similarities between the perceptions of parents and their adolescent children. METHOD: This is a descriptive, cross-sectional study. We used the CP QoL-Teen quality of life questionnaire for adolescents living with cerebral palsy. 60 adolescents who were diagnosed with cerebral palsy and receive conductive education took part in the research together with their parents. The caregivers answered the proxy version of the CP QoL Teen questionnaire. RESULTS: In the population we examined, there is no significant difference between the answers given by parents and teenagers. The highest agreement was found in the chapter of social wellbeing (p = 0.982). CONCLUSIONS: This study highlights the importance of social relationships in achieving a better quality of life for teenagers living with cerebral palsy. Furthermore, it also points out the high adaptability of the relationship between parents and their adolescent children. Orv Hetil. 2023; 164(24): 948-953.

Exploring the quality of life of adolescents with Cerebral Palsy participating in conductive education around the Pannonian Basin.

INTRODUCTION: Quality of life (QoL) is a concept that includes physical, psychological, social, spiritual, and other domains of functioning. Good QoL is a fundamental goal of treatment for Cerebral Palsy (CP), therefore it is an outstanding goal of Conductive Education (CE) as well. CE is a Hungarian method that combines special education and rehabilitation for people living with CP. OBJECTIVE: We aimed to compare the opinions and views about the life of teenagers from the perspective of adolescents and their caregivers from different socio-cultural backgrounds. METHOD: It was a descriptive, cross-sectional study. We used the Cerebral Palsy Quality of Life for the adolescent questionnaire (CP QoL -Teen) to measure QoL, which was translated into Hungarian and validated by Semmelweis University in 2017. Our study included 20 young adolescents (mean age 16) with CP and their caregivers living in Hungary (n1 = 40) and 20 Hungarian-speaking families (n2 = 40) from surrounding countries: Slovakia, Romania, and Ukraine (mean age 14.5). All the families are participating in CE. RESULTS: There was no significant divergence in the whole QoL score between the groups. Nonetheless, we found an outstanding difference in the Hungarian groups' 'Feelings about functioning' domain between teens and caregivers. A significant proportion of Hungarian teens-although living with greater pain-are less concerned about their illness (R = -0.754). 85% of responders study at segregated schools offering CE. CONCLUSION: The study shed new light on the importance of a personalized form of education and on the weight of the positive effects of segregated education. Personalized education can develop the patients' QoL.

On the vibrations of formic acid predicted from first principles.

In this article, we review recent first principles, anharmonic studies on the molecular vibrations of gaseous formic acid in its monomer form. Transitions identified as fundamentals for both cis- and trans form reported in these studies are collected and supported by results from high-resolution experiments. Attention is given to the effect of coordinate coupling on the convergence of the computed vibrational states.

Prolongation of cortical sleep spindles during hippocampal interictal epileptiform discharges in epilepsy patients.

OBJECTIVE: Memory deficits are frequent among patients with epilepsies affecting the temporal lobe. Hippocampal interictal epileptic discharges (hIEDs), the presumed epileptic exaggeration of sharp wave-ripples (SWRs), are known to contribute to memory dysfunction, but the potential underlying mechanism is unknown. The precise temporal coordination between hippocampal SWRs and corticothalamic spindles during sleep is critical for memory consolidation. Moreover, previous investigation indicated that hIEDs induce neocortical spindlelike oscillation. In the present study, we aimed to assess the influence of hIEDs on neocortical spindles. METHODS: We analyzed the spindle characteristics (duration, amplitude, frequency) of 21 epilepsy patients implanted with foramen ovale (FO) electrodes during a whole night sleep. Scalp sleep spindles were categorized based on their temporal relationship to hIEDs detected on the FO electrodes. Three groups were created: (1) spindles coinciding with hIEDs, (2) spindles "induced" by hIEDs, and (3) spindles without hIED co-occurrence. RESULTS: We found that spindles co-occurring with hIEDs had altered characteristics in all measured properties, lasted longer by 126 ± 48 ms (mean ± SD), and had higher amplitude by 3.4 ± 3.2 µV, and their frequency range shifted toward the higher frequencies within the 13-15-Hz range. Also, hIED-induced spindles had identical oscillatory properties to spindles without any temporal relationships with hIEDs. In more than half of our subjects, clear temporal coherence was revealed between hIEDs and spindles, but the direction of the coupling was patient-specific. SIGNIFICANCE: We investigated the effect of hippocampal IEDs on neocortical spindle activity and found spindle alterations in cases of spindle-hIED co-occurrence, but not in cases of hIED-initiated spindles. We propose that this is a marker of a pathologic process, where IEDs may have direct effect on spindle generation. It could mark a potential mechanism whereby IEDs disrupt memory processes, and also provide a potential therapeutic target to treat memory disturbances in epilepsy.

PET/MRI in the Presurgical Evaluation of Patients with Epilepsy: A Concordance Analysis.

The aim of our prospective study was to evaluate the clinical impact of hybrid [18F]-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F]-FDG PET/MRI) on the decision workflow of epileptic patients with discordant electroclinical and MRI data. A novel mathematical model was introduced for a clinical concordance calculation supporting the classification of our patients by subgroups of clinical decisions. Fifty-nine epileptic patients with discordant clinical and diagnostic results or MRI negativity were included in this study. The diagnostic value of the PET/MRI was compared to other modalities of presurgical evaluation (e.g., electroclinical data, PET, and MRI). The results of the population-level statistical analysis of the introduced data fusion technique and concordance analysis demonstrated that this model could be the basis for the development of a more accurate clinical decision support parameter in the future. Therefore, making the establishment of "invasive" (operable and implantable) and "not eligible for any further invasive procedures" groups could be much more exact. Our results confirmed the relevance of PET/MRI with the diagnostic algorithm of presurgical evaluation. The introduction of a concordance analysis could be of high importance in clinical and surgical decision-making in the management of epileptic patients. Our study corroborated previous findings regarding the advantages of hybrid PET/MRI technology over MRI and electroclinical data.

Diagnostic value of MRI in the presurgical evaluation of patients with epilepsy: influence of field strength and sequence selection: a systematic review and meta-analysis from the E-PILEPSY Consortium.

MRI is a cornerstone in presurgical evaluation of epilepsy. Despite guidelines, clinical practice varies. In light of the E-PILEPSY pilot reference network, we conducted a systematic review and meta-analysis on the diagnostic value of MRI in the presurgical evaluation of epilepsy patients. We included original research articles on diagnostic value of higher MRI field strength and guideline-recommended and additional MRI sequences in detecting an epileptogenic lesion in adult or paediatric epilepsy surgery candidates. Lesion detection rate was used as a metric in meta-analysis. Eighteen studies were included for MRI field strength and 25 for MRI sequences, none were free from bias. In patients with normal MRI at lower-field strength, 3T improved lesion detection rate by 18% and 7T by 23%. Field strengths higher than 1.5T did not have higher lesion detection rates in patients with hippocampal sclerosis (HS). The lesion detection rate of epilepsy-specific MRI protocols was 83% for temporal lobe epilepsy (TLE) patients. Dedicated MRI protocols and evaluation by an experienced epilepsy neuroradiologist increased lesion detection. For HS, 3DT1, T2, and FLAIR each had a lesion detection rate at around 90%. Apparent diffusion coefficient indices had a lateralizing value of 33% for TLE. DTI fractional anisotropy and mean diffusivity had a localizing value of 8% and 34%. A dedicated MRI protocol and expert evaluation benefits lesion detection rate in epilepsy surgery candidates. If patients remain MRI negative, imaging at higher-field strength may reveal lesions. In HS, apparent diffusion coefficient indices may aid lateralization and localization more than increasing field strength. DTI can add further diagnostic information. For other additional sequences, the quality and number of studies is insufficient to draw solid conclusions. Our findings may be used as evidence base for developing new high-quality MRI studies and clinical guidelines.

Excited-State DMRG Made Simple with FEAST.

We introduce DMRG[FEAST], a new method for optimizing excited-state many-body wave functions with the density matrix renormalization group (DMRG) algorithm. Our approach applies the FEAST algorithm, originally designed for large-scale diagonalization problems, to matrix product state wave functions. We show that DMRG[FEAST] enables the stable optimization of both low- and high-energy eigenstates, therefore overcoming the limitations of state-of-the-art excited-state DMRG algorithms. We demonstrate the reliability of DMRG[FEAST] by calculating anharmonic vibrational excitation energies of molecules with up to 30 fully coupled degrees of freedom.

Whole Exome Sequencing in a Series of Patients with a Clinical Diagnosis of Tuberous Sclerosis Not Confirmed by Targeted TSC1/TSC2 Sequencing.

BACKGROUND: Approximately fifteen percent of patients with tuberous sclerosis complex (TSC) phenotype do not have any genetic disease-causing mutations which could be responsible for the development of TSC. The lack of a proper diagnosis significantly affects the quality of life for these patients and their families. METHODS: The aim of our study was to use Whole Exome Sequencing (WES) in order to identify the genes responsible for the phenotype of nine patients with clinical signs of TSC, but without confirmed tuberous sclerosis complex 1/ tuberous sclerosis complex 2 (TSC1/TSC2) mutations using routine molecular genetic diagnostic tools. RESULTS: We found previously overlooked heterozygous nonsense mutations in TSC1, and a heterozygous intronic variant in TSC2. In one patient, two heterozygous missense variants were found in polycystic kidney and hepatic disease 1 (PKHD1), confirming polycystic kidney disease type 4. A heterozygous missense mutation in solute carrier family 12 member 5 (SLC12A5) was found in one patient, which is linked to cause susceptibility to idiopathic generalized epilepsy type 14. Heterozygous nonsense variant ring finger protein 213 (RNF213) was identified in one patient, which is associated with susceptibility to Moyamoya disease type 2. In the remaining three patients WES could not reveal any variants clinically relevant to the described phenotypes. CONCLUSION: Patients without appropriate diagnosis due to the lack of sensitivity of the currently used routine diagnostic methods can significantly profit from the wider application of next generation sequencing technologies in order to identify genes and variants responsible for their symptoms.

The role of hybrid FDG-PET/MRI on decision-making in presurgical evaluation of drug-resistant epilepsy.

BACKGROUND: When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20-65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. METHODS: In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. RESULTS: The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. CONCLUSIONS: The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. TRIAL REGISTRATION: Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. TRIAL REGISTRATION NUMBER: 008899/2016/OTIG . Date of registration: 08 February 2016.

Changes of the outcomes of epilepsy surgery within 10 years in the National Institute of Clinical Neurosciences, Hungary / Az epilepsziasebészet eredményességének változása 2006 és 2016 között az Országos Klinikai Idegtudományi Intézetben.

Összefoglaló. Bevezetés és célkituzés: A terápiarezisztens fokális epilepsziák sebészeti kezelése elterjedten használt kezelési lehetoség. Célunk az epilepsziasebészet-hatékonyság változásának vizsgálata egy évtizednyi távlatból a budapesti centrumban. Módszerek: Az Országos Klinikai Idegtudományi Intézetben reszektív epilepsziasebészeti beavatkozásokon átesett fokális epilepsziás betegek adatai kerültek feldolgozásra. A vizsgált 10 év beteganyagát két periódusra osztottuk a mutét idopontja szerint (2006-2010 és 2011-2016). Vizsgálati szempontjaink: demográfiai adatok, az epilepszia kezdete és típusa, mágnesesrezonancia-lelet, preoperatív rohamfrekvencia, mutéttípus és szövettani lelet. Az epileptológiai kimenetelt az Engel-klasszifikáció alapján értékeltük. Eredmények: Epilepsziasebészeti beavatkozás 187 betegen történt, akik közül 137-nél került sor reszekciós mutétre. A betegek 65%-ában temporalis, 18%-ában frontalis, míg 7%-ában olyan multilobaris epilepszia igazolódott, mely a temporalis vagy a frontalis lebenyt érintette. Teljes rohammentességet (Engel I/A) az 1. évben 68%-ban, a 2. évben 64%-ban, míg az 5. évben 63%-ban mértünk. A két intervallum összehasonlításakor az 1 éves rohammentesség aránya 60%-ról (temporalis: 67%, extratemporalis: 50%) 73%-ra (temporalis: 79%, extratemporalis: 62%) javult a második periódusban. Az etiológia szempontjából a hippocampalis sclerosis aránya 28%-ról 14%-ra csökkent, a fokális corticalis dysplasiák aránya 22%-ról 31%-ra növekedett. Következtetés: A sebészeti kezelés fokális epilepsziák esetén - alapos elozetes kivizsgálást követoen - általában biztonságos és a legnagyobb arányban sikeres beavatkozás. A legkedvezobb kimenetel temporalis lokalizációban érheto el. A hatékonyság az évek során egyre javuló tendenciát mutatott az egyre nehezebb sebészeti esetek ellenére. Ez magyarázható a sebészeti technikák fejlodésével, illetve a jobb, mutét elotti elektrofiziológiai és képalkotó technikákkal, amelyek bevezetésével pontosabb lokalizáció adható. Orv Hetil. 2021; 162(6): 219-226. INTRODUCTION AND OBJECTIVE: The surgical treatment of medically intractable focal epilepsies is a well established practice. Our aim was to examine the efficacy of epilepsy surgery within a decade long period in our centre in Budapest. METHODS: Data of drug-resistant patients with resective epilepsy surgery in the National Institute of Clinical Neurosciences were evaluated. The examined 10-year period was divided based on the year of the operation in two parts (2006-2010 and 2011-2016). The following data were collected: demography, beginning and type of epilepsy, magnetic resonance, preoperative seizure frequency, type of surgery and histology. Epileptological outcome was based on modified Engel's classification. RESULTS: Out of 187 surgeries, we identified 137 patients with resective intervention: 65% temporal lobe, 18% frontal, and 7% multilobar epilepsy. Seizure-freedom (Engel I/A) was 68% in the first postoperative year, 64% in the second, and 63% in the fifth year. In the first period, 1-year seizure freedom was 60% (temporal: 67% extratemporal: 50%), while in the second period it was 73% (temporal 79%, extratemporal 62%). Hippocampal sclerosis ratio dropped from 28% to 14%, while focal cortical dysplasia ratio increased from 22% to 31%. CONCLUSION: Surgical treatment in focal epilepsy - after thorough presurgical evaluation - is generally safe and successful. The most favorable outcome is in temporal localization. The efficacy tended to improve over time despite of the more challenging cases. This can be explained with the development of surgical techniques and improvement of presurgical localization. Orv Hetil. 2021; 162(6): 219-226.

Low-grade epilepsy-associated tumour management with or without presurgical evaluation: a multicentre, retrospective, observational study of postsurgical epilepsy outcome.

Low-grade epilepsy-associated neuroepithelial tumours (LEATs) encompass the broad spectrum of tumours associated with epilepsy. Since the postsurgical seizure outcome in LEATs is favourable, it is speculated that epileptological presurgical evaluation (EPE) might not be required for patients with LEATs. A multicentre study involving referring epilepsy and neurosurgery centres was performed, aimed at evaluating postsurgical epilepsy outcome in patients with LEATs, with and without EPE, including long-term video-EEG monitoring (vEEGM). In total, 149 surgically treated patients were enrolled (age: 31±14 years; age at surgery: 26.4±13.1 years; males; 55.7%) with histopathological confirmation of LEATs and follow-up of more than six months. All patients had undergone standard assessment: clinical, routine EEG and brain MRI. In addition to vEEGM, EPE included other additional investigations. Epileptologists did not assess patients treated in neurosurgical centres. The EPE was performed in 51% of patients. Histopathological diagnosis revealed ganglioglioma in 43.6%, DNET in 32.9%, pilocytic astrocytoma in 17.4%, and others in 6.1% of patients. The majority of patients were seizure-free (ILAE epilepsy surgery outcome Class 1; 71.1%). The median follow-up period was 36 months. Patients who were rendered seizure-free were younger (mean age: 24.2±12.2) than those who were not seizure-free (31.8±14.0) (p=0.001). No difference was identified between evaluated and non-evaluated patients with respect to seizure freedom (p=0.45). EPE patients had a longer epilepsy duration (median: 10 years) and a higher proportion of drug resistance (73.6%) compared to non-evaluated patients (median: two years; 26.4%) (p<0.001). Based on a significant difference in major clinical variables, that may well affect postoperative results, the similar postsurgical seizure outcome in groups with and without EPE observed in our study should be considered with caution, and conclusions as to whether there is value in formal presurgical evaluation in LEAT patients cannot be drawn. Our data strongly encourage the clear need for continued discussion around such patients at epilepsy management conferences.

A European questionnaire survey on epilepsy monitoring units' current practice for postoperative psychogenic nonepileptic seizures' detection.

BACKGROUND: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES. METHODS: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project. RESULTS: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 ( ±â€¯19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 ±â€¯7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project. CONCLUSION: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES.

EEG in fitness to drive evaluations in people with epilepsy - Considerable variations across Europe.

PURPOSE: Epilepsy patients consider driving issues to be one of their most serious concerns. Ideally, decisions regarding fitness to drive should be based upon thorough evaluations by specialists in epilepsy care. In 2009, an EU directive was published aiming to harmonize evaluation practices within European countries, but, despite these recommendations, whether all epileptologists use the same criteria is unclear. We therefore conducted this study to investigate routine practices on how epileptologists at European epilepsy centers evaluate fitness to drive. METHODS: A questionnaire was sent to 63 contact persons identified through the European Epi-Care and the E-pilepsy network. The questionnaire addressed how fitness-to-drive evaluations were conducted, the involvement of different professionals, the use and interpretation of EEG, and opinions on existing regulations and guidelines. RESULTS: The questionnaire was completed by 35 participants (56 % response rate). Results showed considerable variation regarding test routines and the emphasis placed on the occurrence and extent of epileptiform discharges revealed by EEG. 82 % of the responders agreed that there was a need for more research on how to better evaluate fitness-to-drive in people with epilepsy, and 89 % agreed that regulations on fitness to drive evaluations should be internationally coordinated. CONCLUSION: Our survey showed considerable variations among European epileptologists regarding use of EEG and how findings of EEG pathology should be assessed in fitness-to-drive evaluations. There is a clear need for more research on this issue and international guidelines on how such evaluations should be carried out would be of value.

Lamotrigine Induces Tremor among Epilepsy Patients Probably via Cerebellar Pathways.

Lamotrigine, a frequently used antiepileptic drug, inhibits voltage-gated sodium-channels. By suppressing the release of glutamate and aspartate, lamotrigine acts as a membrane stabilizer, and it is also effective in bipolar disorder and migraine. However, lamotrigine is known to induce tremor among 4-10% of patients. We examined the lamotrigine-induced tremor in 28 epilepsy patients (age: 38.06 ± 13.56 years; 24 females and 4 males) receiving lamotrigine monotherapy and compared the data to 30 age- and sex-matched controls (age: 33.06 ± 10.71 years; 25 females and 5 males). Tremor was visually assessed by clinical tremor rating scales. Quantitative characteristics (intensity, center frequency and frequency dispersion) which are regularly used to differentiate various tremor syndromes were measured by validated, sensitive biaxial accelerometry in resting, postural and intentional positions. Regularity of repetitive finger and hand movements and reaction time were also determined. Data were statistically analyzed. Clinical tremor rating scales detected pathological tremor in three patients (10%), while accelerometry revealed tremor in seven patients (25%). Center frequency of patients with pathological tremor was similar to controls, but the frequency dispersion was significantly lower and tremor intensity was significantly higher in both postural and intentional positions. Rhythmic movements and reaction time were normal. Our results show that objective measurements detect pathological intention tremor in 25% of epilepsy patients receiving lamotrigine monotherapy. Quantitative characteristics suggest the involvement of the cerebellum in the pathomechanism of lamotrigine-induced tremor. Determining the parameters of drug-induced tremor syndromes might help to understand the complex action of tremor generator networks.

[ECG pearl: tonic-clonic seizure detected by implantable loop recorder]. / EKG-gyöngyszem: tónusos-clonusos epilepsziás roham kimutatása implantábilis loop recorderrel.

A 52-year-old woman is presented with repetitive transient loss of consciousness. Implantable loop recorder (ILR) recorded muscle artifacts during the generalized tonic-clonic seizures. Seizure was diagnosed and antiepileptic drug was started. The patient has been asymptomatic for 9 months. Orv Hetil. 2019; 160(29): 1143-1145.

Reflex seizure triggering: Learning about seizure producing systems.

AIM: We aim to study the mechanism of reflex seizure triggering in close link with the system-epilepsy concept. METHOD: We use data and theories presented in the literature and scrutinize a few illustrative cases. CONCLUSIONS: The prerequisite of seizure triggering is an epilepsy-prone brain network. When it is activated, it may produce seizures manifesting the function(s) of the same system. Beyond classical reflex seizures triggered by sensory-motor stimuli, we extend the reflex-epilepsy concept to seizures induced by the normal activation of epilepsy-prone systems e.g. praxis-induced seizures and those of sleep/wake system epilepsies elicited by falling asleep (absences) or arousals from NREM sleep (seizures of genetic frontal lobe epilepsy). We suggest that normal functioning of epilepsy-prone systems may trigger seizures in epilepsies in general.

Perisylvian epileptic network revisited.

We overview here the new data about the epileptic spectrum disorders within the frame of perisylvian epileptic network since our first trial to synthetize knowledge about this system epilepsy (Halász et al., 2005). We found evidences for a continual features relating together syndromes constituting this spectrum disorder in several fields: in sharing genetic origin, in common perisylvian human communication circuitry, in NREM sleep related potentiation of interictal epileptiform discharges of the centro-temporal spike phenomenon and in the discharge related cognitive impairment, reflecting functional deficits in human communication abilities. The transformation of a part of the children to develop into a malignant course with different degree of residual cognitive loss, through compromising sleep plastic functions, by the epileptic discharges during sleep, beside pure genetic origin, is still under research. Both factual data and new conceptual approaches helps understand better the developmental childhood epilepsies.

Ictal piloerection is associated with high-grade glioma and autoimmune encephalitis-Results from a systematic review.

PURPOSE: To comprehensively analyze ictal piloerection (IP) in a large number of subjects. METHODS: We performed a systematic review on case report studies of patients diagnosed with IP (1929-2017) with additional cases included from the Department of Neurology of University of Pécs, the National Institute of Clinical Neurosciences, and Odense University Hospital. Each included case was characterized regarding patient history, IP seizure characteristics, diagnostic work-up, and therapy. Comparative analyses were also carried out based on sex and pathology. RESULTS: Altogether, 109 cases were included. We observed a strong male predominance (p < 0.001). The mean age at onset of epilepsy was 39.5 ± 20.7 years (median: 38, IQR:24-57). The seizure onset zone was temporal (p < 0.001), and was lateralized to the ipsilateral hemisphere in unilateral localization (p = 0.001). The seizure was accompanied by cold shiver in 53%, and by other autonomic symptoms in 47% of cases. In 53% of patients, IP never progressed into complex partial or generalized tonic-clonic seizure; 16% of the patients reported occasional, and 31% regular generalization. Seizure frequency was higher among females (median:25/day, IQR:3-60) than among males (median:3/day, IQR:1-11) (p = 0.017). The two most common underlying pathologies were limbic encephalitis (23%) and astrocytoma (23%, among them 64% WHO III-IV astrocytoma). CONCLUSION: IP was particularly associated with autoimmune encephalitis and high-grade glioma, suggesting IP's particular clinical importance in directing diagnostic work-up.