Papers by Christoph Kellinghaus
Natural History and Developmental Trajectories of Individuals With Disease-Causing Variants in STXBP1
Neurology, Jul 5, 2023
Background and ObjectivesPathogenic variants inSTXBP1are among the major genetic causes of neurod... more Background and ObjectivesPathogenic variants inSTXBP1are among the major genetic causes of neurodevelopmental disorders. Despite the increasing number of individuals diagnosed without a history of epilepsy, little is known about the natural history and developmental trajectories in this subgroup and endpoints for future therapeutic studies are limited to seizure control.MethodsWe performed a cross-sectional retrospective study using standardized questionnaires for clinicians and caregivers of individuals withSTXBP1-related disorders capturing medical histories, genetic findings, and developmental outcomes. Motor and language function were assessed using Gross Motor Function Classification System (GMFCS) scores and a speech impairment score and were compared within and across clinically defined subgroups.ResultsWe collected data of 71 individuals withSTXBP1-related disorders, including 44 previously unreported individuals. Median age at inclusion was 5.3 years (interquartile range 3.5–9.3) with the oldest individual aged 43.8 years. Epilepsy was absent in 18/71 (25%) of individuals. The range of developmental outcomes was broad, including 2 individuals presenting with close to age-appropriate motor development. Twenty-nine of 61 individuals (48%) were able to walk unassisted, and 24/69 (35%) were able to speak single words. Individuals without epilepsy presented with a similar onset and spectrum of phenotypic features but had lower GMFCS scores (median 3 vs 4,p< 0.01) than individuals with epilepsy. Individuals with epileptic spasms were less likely to walk unassisted than individuals with other seizure types (6% vs 58%,p< 0.01). Individuals with early epilepsy onset had higher speech impairment scores (p= 0.02) than individuals with later epilepsy onset.DiscussionWe expand the spectrum ofSTXBP1-related disorders and provide clinical features and developmental trajectories in individuals with and without a history of epilepsy. Individuals with epilepsy, in particular epileptic spasms, and neonatal or early-onset presented with less favorable motor and language functional outcomes compared with individuals without epilepsy. These findings identify children at risk for severe disease and can serve as comparator for future interventional studies inSTXBP1-related disorders.
Diffusion tensor imaging in patients with juvenile myoclonic epilepsy
P 67 Satisfaction with and reliability of in-hospital video-electroencephalography monitoring systems in epilepsy diagnosis among German epilepsy centers
Clinical Neurophysiology, May 1, 2022
Epilepsy Research, Oct 1, 2013
To determine early changes in bone turnover markers induced by treatment with oxcarbazepine or va... more To determine early changes in bone turnover markers induced by treatment with oxcarbazepine or valproate. Methods: In this prospective study, 31 adults with newly diagnosed epilepsy were included who were started on therapy with either oxcarbazepine (OXC, n = 16, mean age 45.6 years, 37.5% female) or valproate (VPA, n = 15, mean age 42.2 years, 33.3% female). Clinical characteristics were obtained at baseline, after 2 weeks and 3 months. In addition, blood samples were drawn at each visit. Calcium, phosphate, alkaline phosphatase (AP), receptor activator of NF-B ligand (RANKL), osteoprotegerin (OPG), osteocalcin (OC) and cathepsin K were determined. Results: In OXC treated patients, OPG increased by 0.06 pmol/L (p = 0.0004) after 2 weeks and remained elevated by 0.05 pmol/L (p = 0.02) after 3 months. Between 2 weeks and 3 months of OXC treatment, OC increased by 1.98 ng/mL (p = 0.02). During the first 3 months of OXC treatment, total serum AP increased by 11% ± 9% (p = 0.02). Compared to baseline, serum calcium raised by 0.06 mmol/L (p = 0.04) after 2 weeks and by 0.07 mmol/L (p = 0.004) after 3 months of OXC treatment. In VPA treated patients, a late OPG increase by 0.07 pmol/L (p = 0.007) occurred after 3 months. During the first 3 months of OXC treatment, total serum AP decreased by by
Epilepsy surgery in people with intellectual disability – English Version
Zeitschrift Für Epileptologie, Nov 4, 2022
Aktuelle Neurologie, Sep 13, 2017
Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen. Vervielfältigung nur mit Zustimm... more Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen. Vervielfältigung nur mit Zustimmung des Verlages.
Satisfaction with and reliability of in-hospital video-EEG monitoring systems in epilepsy diagnosis – A German multicenter experience
Clinical Neurophysiology, Sep 1, 2021
OBJECTIVE To analyze satisfaction with and reliability of video-electroencephalography-monitoring... more OBJECTIVE To analyze satisfaction with and reliability of video-electroencephalography-monitoring systems (VEMS) in epilepsy diagnostics. METHODS A survey was conducted between December 2020 and January 2021 among German epilepsy centers using well-established customer satisfaction (CS) and quality assurance metrics. RESULTS Among 16 participating centers, CS with VEMS was low, with only 13% of customers actively recommending their system. Only 50% of users were satisfied with the overall performance of their VEMS, and a low 18% were satisfied with the manufacturer's customer service. User interface, software stability, lack of regular updates, and missing customer-oriented improvements were reported as frequent problems jeopardizing diagnosis in approximately every 10th patient. The greatest potential for improvement was identified for software and hardware stability as well as customer service. CONCLUSION Satisfaction with VEMS and their customer service was low, and diagnostics were regularly affected by software or hardware errors. Even if this can be partly explained by the technical complexity of VEMS, there is an urgent need for improvements with regard to the reliability and durability of system components as well as signal synchrony and data management. SIGNIFICANCE This analysis highlights low consumer satisfaction of users with VEMS and uncovers frequent problems and potential for improvement.
Refractory Status Epilepticus: Risk Factors and Analysis of Intubation in the Multicenter SENSE Registry
Neurology, Aug 10, 2022
Background and ObjectivesRefractory status epilepticus (RSE) bears significant morbidity and mort... more Background and ObjectivesRefractory status epilepticus (RSE) bears significant morbidity and mortality. Therapy escalation and in some cases intubation are recommended. Most existing studies are retrospective and focus on intensive care units. We aimed to describe routine-care management and analyze determinants of RSE development and outcomes in a large multicenter cohort.MethodsWe performed post hoc analysis of an observational, cohort study, which prospectively registered all consecutive adults with SE at 9 centers from 3 central European countries. Only incident episodes were included. Ongoing SE despite 2 antiseizure medications was defined as RSE. Patients intubated during first-line or second-line treatments were excluded. Variables investigated included demographics, severity (Status Epilepticus Severity Score), etiology, and guideline-compliant treatment (defined as fixed minimum doses). Outcome parameters included survival and mRS at baseline, and discharge (good: 0–2, or absence of worsening compared with prehospitalization).ResultsAmong 1,179 SE episodes from 1,049 adults, 996 patients were eligible (median age: 70 years, 52% female), of which 545 (54.7%) developed RSE. RSE was associated with higher baseline mRS (p< 0.001) and treatment deviation from guidelines (p< 0.001, OR 0.09; 95% CI 0.06–0.1). Good outcomes were observed in 52.7% of refractory patients, correlating with lower status epilepticus severity (p< 0.001), absence of acute etiology (p< 0.001, OR 0.5; 95% CI 0.3–0.7), adequate first-line benzodiazepine dose (p< 0.001, OR 2.5; 95% CI 1.6–4.0), shorter durations of SE and hospitalization (bothp< 0.001), and lack of intubation (p< 0.001, OR 0.4; 95% CI 0.3–0.6). Most (71.7%) refractory patients were not intubated. Intubation was associated with younger age (p= 0.006), more severe consciousness disturbances (p< 0.001, OR 3.2; 95% CI 2.1–4.8), more severe SE types (p< 0.001), higher severity score (p= 0.009), acute etiologies (p= 0.01, OR 1.6; 95% CI 1.1–2.4), more antiseizure medications (p< 0.001), initial treatment after shorter latency (p= 0.01), worse outcomes (p< 0.001, OR 0.4; 95% CI 0.4–0.6), and longer hospitalizations (p< 0.001).DiscussionVariables associated with RSE were identified, some potentially preventable. More than 70% of RSE were treated without intubation, suggesting that focal RSE without deep impairment of consciousness, in older patients, may be successfully treated outside ICUs.Trial Registration InformationOriginal cohort study registered at the German Clinical Trials Register (DRKS00000725).
Journal of Neurology, Neurosurgery, and Psychiatry, Jun 1, 2004
Background: Piloerection is a rare clinical symptom described during seizures. Previous reports s... more Background: Piloerection is a rare clinical symptom described during seizures. Previous reports suggested that the temporal lobe is the ictal onset zone in many of these cases. One case series concluded that there is a predominant left hemispheric representation of ictal cold. The aim of this study is to evaluate the localising and lateralising value of pilomotor seizures. Methods: Medical records of patients who underwent video electroencephalogram (EEG) monitoring at the Cleveland Clinic between 1994 and 2001 were reviewed for the presence of ictal piloerection. The clinical history, physical and neurological examination, video EEG data, neuroimaging data, cortical stimulation results, and postoperative follow ups were reviewed and used to define the epileptogenic zone. Additionally, all previously reported cases of ictal piloerection were reviewed. Results: Fourteen patients with ictal piloerection were identified (0.4%). Twelve out of 14 patients had temporal lobe epilepsy. In seven patients (50%), the ictal onset was located in the left hemisphere. Four out of five patients with unilateral ictal piloerection had ipsilateral temporal lobe epilepsy as compared with the ipsilateral side of pilomotor response. Three patients became seizure free after left temporal lobectomy for at least 12 months of follow up. An ipsilateral left leg pilomotor response with simultaneously recorded after-discharges was elicited in one patient during direct cortical stimulation of the left parahippocampal gyrus. Conclusions: Ictal piloerection is a rare ictal manifestation that occurs predominantly in patients with temporal lobe epilepsy. Unilateral piloerection is most frequently associated with ipsilateral focal epilepsy. No hemispheric predominance was found in patients with bilateral ictal piloerection.
Progressive multifokale Leukoenzephalopathie (PML) bei chronisch lymphatischer Leukämie (CLL)
ABSTRACT Die progressive multifokale Leukoenzephalopathie (PML) ist eine durch das JC-Virus hervo... more ABSTRACT Die progressive multifokale Leukoenzephalopathie (PML) ist eine durch das JC-Virus hervorgerufene Leukoenzephalopathie des Zentralnervensystems, die in den letzten Jahren insbesondere als opportunistische ZNS-Infektion bei HIV-Patienten an Bedeutung gewann. Die PML resuliert aus der Reaktivierung des JC-Virus und wird durch längerfristige Immunsuppression ausgelöst. Die mittlere Überlebenszeit der in der Literatur dargestellten Fälle (n=17) von PML bei chronisch lymphatischer Leukämie (CLL) beträgt 4,3 Monate, etablierte Therapieverfahren existieren bislang nicht. Wir berichten über einen Patienten mit CLL, der an einer PML erkrankt ist. Die klinische Symptomatik besteht in einer geringgradigen rechtsseitigen Hemiparese mit Feinmotorikstörung. MR-tomographisch zeigte sich eine typische subkortikale Läsion links hochfrontal, das JC-Virus wurde mittels PCR im Liquor nachgewiesen. Aufgrund positiver Ergebnisse der Behandlung der PML mit Cidofovir bei Patienten mit AIDS wurde diese Therapie eingeleitet. Nach 16-monatiger Behandlung ist kein Progress der PML vorhanden, es zeigte sich eine Regredienz der Läsionen in der MR-Tomographie. Das JC-Virus ist unter Therapie nicht mehr nachweisbar. Verglichen mit der Literatur besteht eine 4fach verlängerte Überlebenszeit. Progressive multifocal leukoencephalopathy (PML) is an infectious disease of the central nervous system caused by the JC virus. Progressive multifocal leukoencephalopathy represents a reactivation of the JC virus after long-standing immunosuppression. Also, PML plays an important role as an opportunistic infection in patients with AIDS. The average time of survival in patients with PML in combination with chronic lymphatic leukemia (CLL) (n=17 in the literature) is 4.3 months, and therapeutic options are not established. We report the case of a patient with CLL and PML. Clinical symptoms are slight hemiparesis of the right side, mainly appearing as a disturbance of motor function. In MRI, a typical subcortical lesion was shown, and JC virus DNA was positive in the CSF by PCR. Because of first positive results in treatment of PML in patients with AIDS, therapy with cidofovir was started. After treatment for 16 months, symptoms are stable, the PML-induced lesions in MRI are in regression, and JC virus DNA is not detectable in the CSF.
Assessment of the antiepileptogenic properties of lamotrigine in a hippocampal stimulation model of prolonged status epilepticus
New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) of unknown aetiology: A comparison of the incomparable?
Seizure-european Journal of Epilepsy, Mar 1, 2022
PURPOSE The discussion is ongoing whether new-onset refractory status epilepticus (NORSE) in adul... more PURPOSE The discussion is ongoing whether new-onset refractory status epilepticus (NORSE) in adults and febrile infection-related epilepsy syndrome (FIRES) in children are one syndrome if the aetiology is unknown. In this study we will compare an adult cohort with NORSE and a paediatric cohort with FIRES in order to determine if they are similar or different. METHODS We retrospectively compared 18 adults with NORSE versus 48 children with FIRES, both cohorts without identifiable cause despite extensive investigations. We analyzed demographic and clinical data using Mann-Whitney-U and χ2- tests. RESULTS NORSE affected more women (78% vs. 42%; P = 0.009) than in FIRES. Median acute hospital stay was longer in FIRES (35 days [interquartile range, IQR=36] vs. 20 days [IQR=19]; P<0.001). FIRES was treated more frequently with coma therapy (82% vs. 28%; P<0.001) and with a higher median number of antiseizure medicines (7 [IQR=5] vs. 4 [IQR=2]; P<0.001). Children with FIRES showed a higher cerebrospinal fluid (CSF) cell count (10 cells/μl; P = 0.002) but a lower CSF protein level than adults with NORSE (48 mg/dl; P = 0.028). Immunotherapy was administered more frequently in FIRES (73% vs. 22%; P<0.001) than in NORSE. Group differences in number of antiseizure medicines after hospital stay (P = 0.229) and in overall mortality (P = 0.327) were not significant. CONCLUSION In our explorative comparison, differences prevailed. NORSE and FIRES should be compared prospectively in age-matched cohorts.
Concurrent recordings of slow DC-potentials and epileptiform discharges: Novel EEG amplifier and signal processing techniques
Journal of Neuroscience Methods
Spreading depression and near-infrared spectroscopy during seizures in patients with medically intractable epilepsy
Biophotonics in Exercise Science, Sports Medicine, Health Monitoring Technologies, and Wearables IV
Making SENSE of what we do – How to bring evidence to clinical practice
Epilepsy & Behavior
Neurological Research and Practice
Background Misdiagnosis of seizure-like events (SLE) in emergency situations is common. Here, we ... more Background Misdiagnosis of seizure-like events (SLE) in emergency situations is common. Here, we evaluate whether a single, video-based lesson highlighting distinguishing semiological features can improve the diagnostic accuracy of emergency physicians for epileptic seizures (ES), psychogenic non-epileptic seizures (PNES) and syncopes (SY). Methods 40 emergency physicians (24 anesthetists, nine surgeons and seven internal medicine specialists by primary specialty) participated in a prospective trial on the diagnostic accuracy of SLE. They assessed video-displayed SLE at two time points: before and after a lecture on distinguishing semiological features. In the lecture, semiological features were demonstrated using patient videos, some were acted by the instructor in addition. The increase in correct diagnoses and recognition of distinguishing semiological features were analyzed. Results Before the lesson, 45% of 200 SLE-ratings were correct: 15% of SY (n = 40), 30% of PNES (n = 40),...
Epilepsy surgery in people with intellectual disability – English Version
Zeitschrift für Epileptologie
Seizure Semiology in Antibody-Associated Autoimmune Encephalitis
Neurology - Neuroimmunology Neuroinflammation
Background and ObjectivesTo assess seizure characteristics in antibody (ab)-associated autoimmune... more Background and ObjectivesTo assess seizure characteristics in antibody (ab)-associated autoimmune encephalitis (ab + AE) with the 3 most prevalent abs against N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase (GAD).MethodsMulticenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis.ResultsThree hundred twenty patients with ab + AE were eligible for analysis: 190 NMDAR+, 89 LGI1+, and 41 GAD+. Seizures were present in 113 (60%) NMDAR+, 69 (78%) LGI1+, and 26 (65%) GAD+ patients and as leading symptoms for diagnosis in 53 (28%) NMDAR+, 47 (53%) LGI+, and 20 (49%) GAD+ patients. Bilateral tonic-clonic seizures occurred with almost equal frequency in NMDAR+ (38/51, 75%) and GAD+ (14/20, 70%) patients, while being less common in LGI1+ patients (27/59, 46%). Focal seizures occurred less frequently in NMDAR+ (67/113; 59%) than in LGI1+ (54/69, 78%) or in GAD+ patients (23...
Successful treatment of adult Dravet syndrome patients with cenobamate
Epilepsia
Dravet syndrome (DS) is a rare, drug‐resistant, severe developmental and epileptic encephalopathy... more Dravet syndrome (DS) is a rare, drug‐resistant, severe developmental and epileptic encephalopathy caused by pathogenic variants in the α subunit of the voltage‐gated sodium channel gene SCN1A. Hyperexcitability in DS results from loss of function in inhibitory interneurons. Thus sodium channel blockers are usually contraindicated in patients with DS as they may lead to disease aggravation. Cenobamate (CNB) is a novel antiseizure medication (ASM) with promising rates of seizure freedom in patients with focal‐onset, drug‐resistant epilepsy. CNB blocks persistent sodium currents by promoting the inactive states of sodium channels. In a multi‐center study, we analyzed retrospectively the effect of an add‐on therapy of CNB in adult patients with DS. We report four adult patients with DS in whom the use of CNB resulted in a significant seizure reduction of more than 80%, with a follow‐up of up to 542 days. CNB was the first drug in these patients that resulted in a long‐lasting and signif...
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Papers by Christoph Kellinghaus