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.
- Klíčová slova
- Benign paroxysmal positional vertigo, Case report, Nystagmus, Video-oculography,
- Publikační typ
- kazuistiky MeSH
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.
- Klíčová slova
- Focal drug-resistant epilepsy, Genetic testing, Malformations of cortical development, Paediatric epilepsy surgery, mTOR,
- MeSH
- dítě MeSH
- epilepsie parciální * komplikace MeSH
- epilepsie * genetika chirurgie komplikace MeSH
- fibroblastové růstové faktory genetika MeSH
- genetické testování MeSH
- lidé MeSH
- malformace mozkové kůry * genetika MeSH
- prospektivní studie MeSH
- proteiny aktivující GTPasu genetika MeSH
- proteiny nervové tkáně genetika MeSH
- refrakterní epilepsie * diagnóza genetika chirurgie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- FGF12 protein, human MeSH Prohlížeč
- fibroblastové růstové faktory MeSH
- NPRL3 protein, human MeSH Prohlížeč
- proteiny aktivující GTPasu MeSH
- proteiny nervové tkáně MeSH
- SZT2 protein, human MeSH Prohlížeč
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.
- Klíčová slova
- Epilepsy, Focal cortical dysplasia, Interictal epileptiform discharges, Intracranial EEG, Repetitive discharges, Weibull mixture model,
- MeSH
- Bayesova věta MeSH
- elektroencefalografie škodlivé účinky MeSH
- elektrokortikografie škodlivé účinky MeSH
- epilepsie * chirurgie MeSH
- fokální kortikální dysplazie * MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- malformace mozkové kůry * diagnostické zobrazování chirurgie komplikace MeSH
- refrakterní epilepsie * diagnostické zobrazování chirurgie etiologie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND AND OBJECTIVES: KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants. METHODS: We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details. RESULTS: We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death. DISCUSSION: We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.
- MeSH
- dítě MeSH
- draslíkové kanály ether-a-go-go * genetika MeSH
- epilepsie generalizovaná * genetika MeSH
- epilepsie * genetika MeSH
- fenotyp MeSH
- lidé MeSH
- mutace MeSH
- novorozenec MeSH
- záchvaty genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- draslíkové kanály ether-a-go-go * MeSH
- KCNH5 protein, human MeSH Prohlížeč
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.
- Klíčová slova
- Children, Epilepsy surgery, Opercular-insular region, SEEG,
- MeSH
- dítě MeSH
- elektroencefalografie MeSH
- epilepsie * chirurgie MeSH
- implantované elektrody MeSH
- insulární kortex MeSH
- lidé MeSH
- refrakterní epilepsie * chirurgie MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Epilepsy surgery fails in > 30% of patients with focal cortical dysplasia (FCD). The seizure persistence after surgery can be attributed to the inability to precisely localize the tissue with an endogenous potential to generate seizures. In this study, we aimed to identify the critical components of the epileptic network that were actively involved in seizure genesis. METHODS: The directed transfer function was applied to intracranial EEG recordings and the effective connectivity was determined with a high temporal and frequency resolution. Pre-ictal network properties were compared with ictal epochs to identify regions actively generating ictal activity and discriminate them from the areas of propagation. RESULTS: Analysis of 276 seizures from 30 patients revealed the existence of a seizure-related network reconfiguration in the gamma-band (25-170 Hz; p < 0.005) - ictogenic nodes. Unlike seizure onset zone, resecting the majority of ictogenic nodes correlated with favorable outcomes (p < 0.012). CONCLUSION: The prerequisite to successful epilepsy surgery is the accurate identification of brain areas from which seizures arise. We show that in FCD-related epilepsy, gamma-band network markers can reliably identify and distinguish ictogenic areas in macroelectrode recordings, improve intracranial EEG interpretation and better delineate the epileptogenic zone. SIGNIFICANCE: Ictogenic nodes localize the critical parts of the epileptogenic tissue and increase the diagnostic yield of intracranial evaluation.
- Klíčová slova
- Effective connectivity, Epilepsy, Intracranial EEG, Networks, Outcome, Seizure onset zone,
- MeSH
- dítě MeSH
- dospělí MeSH
- gama rytmus EEG fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- malformace mozkové kůry diagnostické zobrazování patofyziologie chirurgie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozková kůra diagnostické zobrazování patofyziologie chirurgie MeSH
- následné studie MeSH
- nervová síť diagnostické zobrazování patofyziologie chirurgie MeSH
- refrakterní epilepsie diagnostické zobrazování patofyziologie chirurgie MeSH
- retrospektivní studie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: In this study, the authors aimed to determine 1) whether the use of intraoperative electrocorticography (ECoG) affects outcomes and complication rates of children undergoing resective epilepsy surgery; 2) which patient- and epilepsy-related variables might influence ECoG-based surgical strategy; and 3) what the predictors of epilepsy surgery outcomes are. METHODS: Over a period of 12 years, data were collected on pediatric patients who underwent tailored brain resections in the Motol Epilepsy Center. In patients in whom an abnormal ECoG pattern (e.g., spiking, suppression burst, or recruiting rhythm) was not observed beyond presurgically planned resection margins, the authors did not modify the surgical plan (group A). In those with significant abnormal ECoG findings beyond resection margins, the authors either did (group B) or did not (group C) modify the surgical plan, depending on the proximity of the eloquent cortex or potential extent of resection. Using Fisher's exact test and the chi-square test, the 3 groups were compared in relation to epilepsy surgery outcomes and complication rate. Next, multivariate models were constructed to identify variables associated with each of the groups and with epilepsy surgery outcomes. RESULTS: Patients in group C achieved significantly lower rates of seizure freedom compared to groups A (OR 30.3, p < 0.001) and B (OR 35.2, p < 0.001); groups A and B did not significantly differ (p = 0.78). Patients in whom the surgical plan was modified suffered from more frequent complications (B vs A+C, OR 3.8, p = 0.01), but these were mostly minor (duration < 3 months; B vs A+C, p = 0.008). In all cases, tissue samples from extended resections were positive for the presence of the original pathology. Patients with intended modification of the surgical plan (groups B+C) suffered more often from daily seizures, had a higher age at first seizure, had intellectual disability, and were regarded as MR-negative (p < 0.001). Unfavorable surgical outcome (Engel class II-IV) was associated with focal cortical dysplasia, incomplete resection based on MRI and/or ECoG findings, negative MRI finding, and inability to modify the surgical plan when indicated. CONCLUSIONS: Intraoperative ECoG serves as a reliable tool to guide resection and may inform the prognosis for seizure freedom in pediatric patients undergoing epilepsy surgery. ECoG-based modification of the surgical plan is associated with a higher rate of minor complications. Children in whom ECoG-based modification of the surgical plan is indicated but not feasible achieve significantly worse surgical outcomes.
- Klíčová slova
- drug-resistant epilepsy, electrocorticography, epilepsy surgery, epileptogenic zone, interictal epileptiform discharges,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Neurodegeneration with brain iron accumulation constitutes a group of rare progressive movement disorders sharing intellectual disability and neuroimaging findings as common denominators. Beta-propeller protein-associated neurodegeneration (BPAN) represents approximately 7% of the cases, and its first signs are typically epilepsy and developmental delay. We aimed to describe in detail the phenotype of BPAN with a special focus on iron metabolism. MATERIAL AND METHODS: We present a cohort of paediatric patients with pathogenic variants of WD-Repeat Domain 45 gene (WDR45). The diagnosis was established by targeted panel sequencing of genes associated with epileptic encephalopathies (n = 9) or by Sanger sequencing of WDR45 (n = 1). Data on clinical characteristics, molecular-genetic findings and other performed investigations were gathered from all participating centres. Markers of iron metabolism were analysed in 6 patients. RESULTS: Ten children (3 males, 7 females, median age 8.4 years) from five centres (Prague, Berlin, Vogtareuth, Tubingen and Cologne) were enrolled in the study. All patients manifested first symptoms (e.g. epilepsy, developmental delay) between 2 and 31 months (median 16 months). Seven patients were seizure-free (6 on antiepileptic medication, one drug-free) at the time of data collection. Neurological findings were non-specific with deep tendon hyperreflexia (n = 4) and orofacial dystonia (n = 3) being the most common. Soluble transferrin receptor/log ferritin ratio was elevated in 5/6 examined subjects; other parameters of iron metabolism were normal. CONCLUSION: Severity of epilepsy often gradually decreases in BPAN patients. Elevation of soluble transferrin receptor/log ferritin ratio could be another biochemical marker of the disease and should be explored by further studies.
- Klíčová slova
- Beta-propeller protein-associated neurodegeneration, Neurodegeneration with brain iron accumulation WDR45, BPAN, Targeted gene panel sequencing,
- MeSH
- biologické markery krev MeSH
- dítě MeSH
- epilepsie krev genetika metabolismus MeSH
- fenotyp MeSH
- lidé MeSH
- mentální retardace krev genetika metabolismus MeSH
- neurodegenerativní nemoci krev genetika metabolismus MeSH
- pohybové poruchy krev genetika metabolismus MeSH
- poruchy metabolismu železa krev genetika metabolismus MeSH
- transportní proteiny genetika MeSH
- železo krev MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- transportní proteiny MeSH
- WDR45 protein, human MeSH Prohlížeč
- železo MeSH
OBJECTIVE: Resective epilepsy surgery is an established treatment method for children with focal intractable epilepsy, but the use of this method introduces the risk of postsurgical motor deficits. Electrical stimulation mapping (ESM), used to define motor areas and pathways, frequently fails in children. The authors developed and tested a novel ESM protocol in children of all age categories. METHODS: The ESM protocol utilizes high-frequency electric cortical stimulation combined with continuous intraoperative motor-evoked potential (MEP) monitoring. The relationships between stimulation current intensity and selected presurgical and surgery-associated variables were analyzed in 66 children (aged 7 months to 18 years) undergoing 70 resective epilepsy surgeries in proximity to the motor cortex or corticospinal tracts. RESULTS: ESM elicited MEP responses in all children. Stimulation current intensity was associated with patient age at surgery and date of surgery (F value = 6.81, p < 0.001). Increase in stimulation current intensity predicted postsurgical motor deficits (F value = 44.5, p < 0.001) without effects on patient postsurgical seizure freedom (p > 0.05). CONCLUSIONS: The proposed ESM paradigm developed in our center represents a reliable method for preventing and predicting postsurgical motor deficits in all age groups of children. This novel ESM protocol may increase the safety and possibly also the completeness of epilepsy surgery. It could be adopted in pediatric epilepsy surgery centers.
- Klíčová slova
- cortical stimulation, epilepsy surgery, intraoperative monitoring, motor deficits, outcome,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: We aimed first to describe trends in cognitive performance over time in a large patient cohort (n = 203) from a single tertiary centre for paediatric epilepsy surgery over the period of 16 years divided in two (developing-pre-2011 vs. established-post-2011). Secondly, we tried to identify subgroups of epilepsy surgery candidates with distinctive epilepsy-related characteristics that associate with their pre- and post-surgical cognitive performance. Thirdly, we analysed variables affecting pre-surgical and post-surgical IQ/DQ and their change (post- vs. pre-surgical). METHODS: We analysed IQ/DQ data obtained using standardized neuropsychological tests before epilepsy surgery and one year post-surgically, along with details of patient's epilepsy, epilepsy surgery and outcomes in terms of freedom from seizures. Using regression analysis, we described the trend in post-operative IQ/DQ. Cognitive outcomes and the associated epilepsy- and epilepsy surgery-related variables were compared between periods before and after 2011. Using multivariate analysis we analysed the effect of individual variables on pre- and post-operative IQ/DQ and its change. RESULTS: Epilepsy surgery tends to improve post-surgical IQ/DQ, most significantly in patients with lower pre-surgical IQ/DQ, and post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ (Rho = 0.888, p < 0.001). We found no significant difference in pre-, post-surgical IQ/DQ and IQ/DQ change between the periods of pre-2011 and post-2011 (p = 0.7, p = 0.469, p = 0.796, respectively). Patients with temporal or extratemporal epilepsy differed in their pre-surgical IQ/DQ (p = 0.001) and in IQ/DQ change (p = 0.002) from those with hemispheric epilepsy, with no significant difference in post-surgical IQ/DQ (p = 0.888). Groups of patients with different underlying histopathology showed significantly different pre- and post-surgical IQ/DQ (p < 0.001 and p < 0.001 respectively) but not IQ/DQ change (p = 0.345).Variables associated with severe epilepsy showed effect on cognitive performance in multivariate model. DISCUSSION: Post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ and greatest IQ/DQ gain occurs in patients with lower pre-surgical IQ/DQ scores. Cognitive performance was not affected by changes in paediatric epilepsy surgery practice. Pre- and post-operative cognitive performances, as well as patients' potential for cognitive recovery, are highly dependent on the underlying aetiology and epileptic syndrome.
