Psychometric properties of the Czech versions of the Impact of Pediatric Epilepsy Scale (IPES) and Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48).

OBJECTIVE: In order to introduce a complex system of monitoring and evaluation of the heath-related quality of life (HRQoL) of children and adolescents with epilepsy (CWE) and their families in the Czech Republic, we aimed to validate the Czech versions of two appropriate instruments - the Impact of Pediatric Epilepsy Scale (IPES) and the Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48). METHODS: The verification of the 11-item IPES was carried out in the group of parents of 248 CWE aged 2-18 years. One hundred and thirty-five CWE from the given group aged 11-18 years then completed the 48-item QOLIE-AD-48. Internal consistency, test-retest reliability (with a three-month interval) and the factorial structure of the Czech versions were determined and compared with the original instruments. RESULTS: We found that the Czech version of the IPES exhibited very good psychometric properties including high internal consistency (Cronbach's alpha, α, of 0.93), high test-retest reliability (intraclass correlation coefficient, ICC, of 0.76) and the same 3-factor structure as the original instrument. The superiority of this 3-factor solution over the alternate 2-factor model proposed for some language versions of the IPES was determined using confirmatory factor analysis. We found 8 items in the Czech version of the QOLIE-AD-48 belonging to original Attitudes towards epilepsy and Social support subscales that do not fit well with the Czech version due to their low correlation with the total score and insufficient test-retest reliability and should be omitted. For the remaining 40 items, we have determined high internal consistency (α = 0.95) and test-retest reliability (ICC = 0.82). Confirmatory factor analysis revealed that the 6-factor solution derived from the original instrument (without two removed subscales) was appropriate for the Czech version. The individual subscales exhibited high internal consistency with α = 0.61-0.91. The external validation of both instruments was confirmed based on a significant correlation between test results and physicians' reports of the characteristics of the child's epilepsy. CONCLUSIONS: The Czech versions of both instruments studied are reliable and valid, and can be used in the next research focusing on the effect of different treatment approaches on the HRQoL of CWE and their families.

An immunotherapy effect analysis in Rasmussen encephalitis.

BACKGROUND: Immune-mediated mechanisms substantially contribute to the Rasmussen encephalitis (RE) pathology, but for unknown reasons, immunotherapy is generally ineffective in patients who have already developed intractable epilepsy; overall laboratory data regarding the effect of immunotherapy on patients with RE are limited. We analyzed multiple samples from seven differently treated children with RE and evaluated the effects of immunotherapies on neuroinflammation. Immunotherapy was introduced to all patients at the time of intractable epilepsy and they all had to undergo hemispherothomy. METHODS: Immunohistochemistry, flow cytometry, Luminex multiplex bead and enzyme-linked immunosorbent assay techniques were combined to determine: 1) inflammatory changes and lymphocyte subpopulations in 45 brain tissues; 2) lymphocyte subpopulations and the levels of 12 chemokines/cytokines in 24 cerebrospinal fluid (CSF) samples and 30 blood samples; and 3) the dynamics of these parameters in four RE patients from whom multiple samples were collected. RESULTS: Sustained T cell-targeted therapy with cyclophosphamide, natalizumab, alemtuzumab, and intrathecal methotrexate (ITMTX), but not with azathioprine, substantially reduced inflammation in brain tissues. Despite the therapy, the distributions of CD8+ T cells and the levels of C-X-C motif ligand (CXCL) 10, CXCL13, and B cell activating factor (BAFF) in patients' CSF remained increased compared to controls. A therapeutic approach combining alemtuzumab and ITMTX was the most effective in producing simultaneous reductions in histopathological inflammatory findings and in the numbers of activated CD8+ T cells in the brain tissue, as well as in the overall CD8+ T cell population and chemokine/cytokine production in the CSF. CONCLUSIONS: We provide evidence that various T cell-targeted immunotherapies reduced inflammation in the brains of RE patients. The observation that intractable epilepsy persisted in all of the patients suggests a relative independence of seizure activity on the presence of T cells in the brain later in the disease course. Thus, new therapeutic targets must be identified. CXCL10, CXCL13 and BAFF levels were substantially increased in CSF from all patients and their significance in RE pathology remains to be addressed.

Early Manifestation of Benign Paroxysmal Positional Vertigo: A Case Report.

Introduction: Benign paroxysmal positional vertigo (BPPV) is an inner ear disorder with a heterogeneous etiology, often linked to preceding infections, head injuries, or vestibular neuronitis. While it is commonly observed in the elderly, its occurrence in the pediatric population is rare. To our knowledge, there have been no reported cases of BPPV in patients younger than 5 years. Case Presentation: A 4.5-month-old female infant was admitted with episodes of paroxysmal nystagmus. Parents reported fast horizontal eye movements lasting up to 30 s, with one episode accompanied by vomiting. Comprehensive differential diagnosis was considered from epileptic nystagmus to intoxications and both central and peripheral vestibular etiologies. During the observation on ward, connection between the baby's positioning and nystagmus was identified. The diagnostic roll test confirmed a transient positional geotropic nystagmus. The diagnosis aligned with BPPV characteristics, pointing to the right lateral semicircular canal canalolithiasis. A successful Lempert roll maneuver was performed with prompt effect. To further support the diagnosis and research, we introduced a semiautomatic video-oculography method. Conclusion: This case highlights a rare instance of BPPV in an infant. The clinical findings combined with the effectiveness of the repositioning maneuvers support the diagnosis of right lateral semicircular canal lithiasis. Despite the rarity of this condition in such a young-age group, the need for thorough diagnostic evaluations is emphasized. In order to document the case, we also present a semiautomatic video analysis pipeline for analyzing abnormal eye movements in a home setting.

Distinct patterns of interictal intracranial EEG in focal cortical dysplasia type I and II.

OBJECTIVE: Focal cortical dysplasia (FCD) is the most common malformation causing refractory focal epilepsy. Surgical removal of the entire dysplastic cortex is crucial for achieving a seizure-free outcome. Precise presurgical distinctions between FCD types by neuroimaging are difficult, mainly in patients with normal magnetic resonance imaging findings. However, the FCD type is important for planning the extent of surgical approach and counselling. METHODS: This study included patients with focal drug-resistant epilepsy and definite histopathological FCD type I or II diagnoses who underwent intracranial electroencephalography (iEEG). We detected interictal epileptiform discharges (IEDs) and their recruitment into repetitive discharges (RDs) to compare electrophysiological patterns characterizing FCD types. RESULTS: Patients with FCD type II had a significantly higher IED rate (p < 0.005), a shorter inter-discharge interval within RD episodes (p < 0.003), sleep influence on decreased RD periodicity (p < 0.036), and longer RD episode duration (p < 0.003) than patients with type I. A Bayesian classifier stratified FCD types with 82% accuracy. CONCLUSION: Temporal characteristics of IEDs and RDs reflect the histological findings of FCD subtypes and can differentiate FCD types I and II. SIGNIFICANCE: Presurgical prediction of FCD type can help to plan a more tailored surgical approach in patients with normal magnetic resonance findings.

Genetic testing in children enrolled in epilepsy surgery program. A real-life study.

OBJECTIVE: Although genetic causes of drug-resistant focal epilepsy and selected focal malformations of cortical development (MCD) have been described, a limited number of studies comprehensively analysed genetic diagnoses in patients undergoing pre-surgical evaluation, their outcomes and the effect of genetic diagnosis on surgical strategy. METHODS: We analysed a prospective cohort of children enrolled in epilepsy surgery program over January 2018-July 2022. The majority of patients underwent germline and/or somatic genetic testing. We searched for predictors of surgical outcome and positive result of germline genetic testing. RESULTS: Ninety-five patients were enrolled in epilepsy surgery program and 64 underwent resective epilepsy surgery. We ascertained germline genetic diagnosis in 13/74 patients having underwent germline gene testing (pathogenic or likely pathogenic variants in CHRNA4, NPRL3, DEPDC5, FGF12, GRIA2, SZT2, STXBP1) and identified three copy number variants. Thirty-five patients underwent somatic gene testing; we detected 10 pathogenic or likely pathogenic variants in genes SLC35A2, PTEN, MTOR, DEPDC5, NPRL3. Germline genetic diagnosis was significantly associated with the diagnosis of focal epilepsy with unknown seizure onset. SIGNIFICANCE: Germline and somatic gene testing can ascertain a definite genetic diagnosis in a significant subgroup of patients in epilepsy surgery programs. Diagnosis of focal genetic epilepsy may tip the scales against the decision to proceed with invasive EEG study or surgical resection; however, selected patients with genetic focal epilepsies associated with MCD may benefit from resective epilepsy surgery and therefore, a genetic diagnosis does not disqualify patients from presurgical evaluation and epilepsy surgery.

May intraoperative detection of stereotactically inserted intracerebral electrodes increase precision of resective epilepsy surgery?

OBJECT: Epilepsy surgery is an effective treatment for selected patients with focal intractable epilepsy. Complete removal of the epileptogenic zone significantly increases the chances for postoperative seizure-freedom. In complex surgical candidates, delineation of the epileptogenic zone requires a long-term invasive video/EEG from intracranial electrodes. It is especially challenging to achieve a complete resection in deep brain structures such as opercular-insular cortex. We report a novel approach utilizing intraoperative visual detection of stereotactically implanted depth electrodes to inform and guide the extent of surgical resection. METHODS: We retrospectively reviewed data of pediatric patients operated in Motol Epilepsy Center between October 2010 and June 2020 who underwent resections guided by intraoperative visual detection of depth electrodes following SEEG. The outcome in terms of seizure- and AED-freedom was assessed individually in each patient. RESULTS: Nineteen patients (age at surgery 2.9-18.6 years, median 13 years) were included in the study. The epileptogenic zone involved opercular-insular cortex in eighteen patients. The intraoperative detection of the electrodes was successful in seventeen patients and the surgery was regarded complete in sixteen. Thirteen patients were seizure-free at final follow-up including six drug-free cases. The successful intraoperative detection of the electrodes was associated with favorable outcome in terms of achieving complete resection and seizure-freedom in most cases. On the contrary, the patients in whom the procedure failed had poor postsurgical outcome. CONCLUSION: The reported technique helps to achieve the complete resection in challenging patients with the epileptogenic zone in deep brain structures.