G. Möddel - Academia.edu (original) (raw)
Papers by G. Möddel
Therapie-Handbuch Grundwerk inkl 6. Lfg., 2007
Purpose To characterize the interaction between language dominance and lateralization of the epil... more Purpose To characterize the interaction between language dominance and lateralization of the epileptic focus for pre- and postoperative Boston Naming Test (BNT) performance in patients undergoing anterior temporal lobectomy (ATL). Methods Analysis of pre- and postoperative BNT scores depending on lateralization of language as measured by the intracarotid amobarbital procedure (IAP) versus lateralization of the temporal lobe epileptic focus. Results Changes between pre- and postoperative BNT performance depended on epilepsy lateralization (effect size = 0.189) with significant decrease in patients undergoing left ATL. Subgroup analysis in these showed that postoperative decline in BNT scores was significant in patients with atypical (n = 14; p <
The recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-... more The recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-oriented approach. Epilepsy syndromes--at least as defined by the ILAE Task Force--group patients according to multiple, usually poorly defined parameters. As a result, these syndromes frequently show significant overlap and may change with patient age. We propose a five-dimensional and patient-oriented approach to epilepsy classification. This approach shifts away from syndrome orientation, using independent criteria in each of the five dimensions similarly to the diagnostic process in general neurology. The main dimensions of this new classification consist of (1) localizing the epileptogenic zone, (2) semiology of the seizure, (3) etiology, (4) seizure frequency, and (5) related medical conditions. These dimensions characterize all information necessary for patient management, are independent parameters, and include information more pertinent than the ILAE axes with regard to patient ...
Klinische Neurophysiologie, 2016
Clinical Neurophysiology, 2015
Clinical Neurophysiology, 2015
Triphasic waves are commonly seen in the EEG of patients with encephalopathy. Although typically ... more Triphasic waves are commonly seen in the EEG of patients with encephalopathy. Although typically associated with metabolic encephalopathy or post-hypoxic damage, they are unspecific in respect of the etiology of brain dysfunction. Here, we present a case report of acute-onset triphasic waves induced by hypercapnia. We report on a 27-year-old male with severe sensory and motor neuropathy, tetraparesis, ataxia, dysarthria, and cognitive impairment of yet unknown etiology since the age of 14 years. The patient was referred to our hospital and admitted to the EEG monitoring unit for differential diagnosis of recurrent episodes of loss of consciousness. At time of admission, a borderline oxygen saturation (SatO2) of around 80% was recorded, attributable to his chronic neuromuscular disease. During the first evening after admission, SatO2 repeatedly dropped below 80%. Oxygen insufflation was initiated by the doctor-on-call and the patient’s vigilance was repeatedly tested throughout the night. At a routine check, the patient was found stuporous. Blood gas analysis showed carbon dioxide partial pressure (pCO2) of 85.6 mmHg and oxygen partial pressure (pO2) of 75.6 mmHg. Emergency bag-valve mask ventilation was started, the patient was intubated, and transferred to the intensive care unit. After several days, the patient was extubated without any new-onset neurological deficit. Polysomnography revealed alveolar hypoventilation, and non-invasive assisted bilevel ventilation treatment was initiated before the patient was discharged home. Upon post hoc review, the EEG during the night after admission showed normal sleep patterns which were replaced by triphasic waves just about 10 min before the patient was found to be stuporous. Upon bag-valve-mask ventilation, the triphasic waves disappeared within 2–3 min, and the EEG showed a normal awake state prior to sedation intubation. This case demonstrates that hypercapnia may induce acute-onset triphasic waves in the EEG which are readily reversible within minutes after assisted ventilation. Moreover, this case illustrates the danger of oxygen insufflation in patients with chronic alveolar hypoventilation. We conclude that our patient suffered from chronic alveolar hypoventilation due to severe neuropathy which resulted in chronic moderate hypercapnia, with respiration triggered by hypoxia alone. When receiving oxygen insufflation, hypoxia-induced respiration failed leading to central hypopnea, acute pCO2 increase and stupor.
Der Nervenarzt
Neurostimulation techniques are applied to reduce the frequency and severity of epileptic seizure... more Neurostimulation techniques are applied to reduce the frequency and severity of epileptic seizures. Class I evidence showed that vagus nerve stimulation (VNS) reduces seizure burden by 25-28% compared to 6-15% in placebo controls. Open-label studies, however, reported much greater efficacy. Since 2010 deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is CE approved for epilepsy therapy in Europe. A multicenter randomized controlled trial reported seizure frequency reduction by 40.4% compared to 14.5% in controls. A significant effect was only found in patients with temporal seizure onset. 13% of stimulated patients became seizure-free for at least 6 months. Possible side-effects include depression (14.8%) and memory impairment (13%). Responsive neurostimulation (RNS) combines an automated seizure detection device with on-demand triggered stimulation of the epileptogenic zone. A randomized controlled trial reported seizure frequency reduction by 37.9% compared to 17.3% in controls. There were no relevant neuropsychological or psychiatric side-effects noted.
Der Nervenarzt
Der Status epilepticus (SE) gehört mit einer jährlichen Inzidenz von 10–20/100.000 Einwohnern zu ... more Der Status epilepticus (SE) gehört mit einer jährlichen Inzidenz von 10–20/100.000 Einwohnern zu den häufigsten Notfällen in der Neurologie. Die Gesamtmortalität liegt abhängig von einer Reihe klinischer Parameter zwischen 10% und 20%. Die Patienten zeigen lang andauernde oder in Serie auftretende motorische Anfälle oder prolongierte Bewusstseinsstörungen bis hin zum Koma. Darüber hinaus können eine Reihe systemischer Komplikationen auftreten, die auch als Folge einer aggressiven medikamentösen Therapie möglich sind. Während sich der überwiegende Teil der SE durch standardisierte Behandlungsalgorithmen unterbrechen lässt, erweisen sich einige SE als refraktär gegen diese Initialtherapie und bedürfen einer intensivmedizinischen Intervention. Hier kommen vornehmlich nicht sedierende Antikonvulsiva und bei Bedarf zusätzlich Injektionsnarkotika zum Einsatz. In Einzelfällen stellen nichtmedikamentöse Therapieansätze (z. B. die Epilepsiechirurgie) eine zusätzliche Behandlungsalternative d...
Therapie-Handbuch Grundwerk inkl 6. Lfg., 2015
Der Nervenarzt, 2003
Attempts to control epileptic seizures by electrical brain stimulation have been performed for 50... more Attempts to control epileptic seizures by electrical brain stimulation have been performed for 50 years. Many different stimulation targets and methods have been investigated. Vagal nerve stimulation (VNS) is now approved for the treatment of refractory epilepsies by several governmental authorities in Europe and North America. However, it is mainly used as a palliative method when patients do not respond to medical treatment and epilepsy surgery is not possible. Numerous studies of the effect of deep brain stimulation (DBS) on epileptic seizures have been performed and almost invariably report remarkable success. However, a limited number of controlled studies failed to show a significant effect. Repetitive transcranial magnetic stimulation (rTMS) also was effective in open studies, and controlled studies are now being carried out. In addition, several uncontrolled reports describe successful treatment of refractory status epilepticus with electroconvulsive therapy (ECT). In summar...
Aktuelle Neurologie, 2014
Parasomnien umfassen eine grose Gruppe unterschiedlicher motorischer Phanomene wahrend des Schlaf... more Parasomnien umfassen eine grose Gruppe unterschiedlicher motorischer Phanomene wahrend des Schlafes. Entsprechend der Internationalen Klassifikation von Schlafstorungen II (ICSD II) werden Parasomnien in Formen unterteilt, die aus dem Non-REM-Schlaf heraus auftreten und Formen, die aus dem REM-Schlaf auftreten. Als andere Parasomnien werden die Formen bezeichnet, bei denen keine feste Zuordnung zu einem Schlafstadium moglich ist. Schlafwandeln, Schlaftrunkenheit und der Pavor nocturnus sind die klinisch wichtigsten Formen der Non-REM Parasomnien. Hauptmerkmal dieser Formen ist der Beginn aus dem Schlafstadium Non-REM 3, dem durch hohen Anteil an Deltaaktivitat gekennzeichneten Tiefschlaf. Die Gesamtpravalenz der Non-REM-Parasomnien bei Erwachsenen wird mit ca. 4% angegeben. Damit ist diese Form der Parasomnien eine klinisch relevante, aber vermutlich unterdiagnostizierte Gruppe von Schlafstorungen. Als besondere Form der Parasomnie gilt neben den Non-REM-Parasomnien die schlafbezogene Essstorung. Diese in die Gruppe der anderen Parasomnien klassifizierte Schlafstorung tritt aus Non-REM-Stadium 2 und 3 auf. Fur alle hier beschriebenen Parasomnien gilt, dass assoziierte Symptome wie Tagesschlafrigkeit, Traumerinnern und nachtliche autonome Aktivierungen haufiger zu finden sind als allgemein angenommen wurde. Die wichtigsten Differenzialdiagnosen des Schlafwandelns und der gesamten Gruppe der Non-REM-Parasomnien sind die REM-Schlaf-assoziierten Parasomnien, wie die REM-Schlaf-Verhaltensstorung und epileptische Anfalle aus dem Schlaf, bspw. bei Patienten mit nachtlicher Frontallappenepilepsie. Da die nachtlichen, motorischen Symptome keine ausreichende und sichere Differenzierung der verschiedenen Differenzialdiagnosen zulassen, stellt die videobasierte Polysomnografie im Schlaflabor den Gold-Standard in der technischen Diagnosestellung dar. Ebenso dient die videobasierte Polysomnografie der Entscheidung zur erweiterten video-basierten elektroenzephalografischen Diagnostik. Vor diesem Hintergrund ist fur die Diagnosestellung von Schlafwandeln und Non-REM-Parasomnien die enge Zusammenarbeit zwischen Schlafmedizinern und Epileptologen empfehlenswert.
Chemokines, a family member of cytokines, have been shown to play a major role in central nervous... more Chemokines, a family member of cytokines, have been shown to play a major role in central nervous system inflammation. Among other chemokines, CXCR3 and its ligand CXCL10 are involved in the pathophysiology of several neuroinflammatory conditions. Most of these conditions are also associated with an increased incidence of seizure or epilepsy. Using age-matched wild-type (WT), as well as CXCR3-receptor-deficient (CXCR3-KO) mice, the present study aimed to investigate the effect of the chemokine CXCL10 and its receptor CXCR3 on synaptic plasticity as well as neuronal activities in hippocampal brain slices. Using field potential and intracellular recordings, the effect of exogenous CXCL10 on tetanus-induced long-term potentiation (LTP) as well as the neuronal spike activity was evaluated in hippocampal CA1 area. Exogenous application of CXCL10 enhanced LTP in WT mice, whereas it exerted no significant effect on CXCR3-KO mice. During intracellular recordings of spontaneous spike activity, exogenous application of CXCL10 significantly enhanced the amplitude, duration, and after-hyperpolarization of action potentials in slices obtained from WT mice compared to CXCR3-KO mice. In addition, CXCR3-KO mice exhibited a lower GABAA-mediated excitation in hippocampal CA1 neurons compared to WT mice. These data show that the inflammatory chemokine CXCL10, probably via its receptor CXCR3, modulates neuronal activity and synaptic plasticity in the hippocampus. CXCL10 may be involved in seizures observed during neuroinflammatory diseases such as meningitis and encephalitis.
Epileptic disorders, 2007
Malformations of cortical development are frequent causes of human refractory epilepsy. The freez... more Malformations of cortical development are frequent causes of human refractory epilepsy. The freeze-lesion model in rats shows histopathological features similar to those found in human polymicrogyria. Previous studies reported in vitro hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed. Neocortical freeze lesions were induced in Sprague-Dawley rat pups (n = 10) on postnatal day 0 or 1 (P0/P1). Sham-operated animals served as controls (n = 10). On P60, animals were implanted with epidural electrodes for long-term video-EEG monitoring (4 weeks). The threshold for pentylenetetrazol-induced seizures was determined. Animals were sacrificed and brain sections processed for histological staining and in vitro electrophysiological recordings. Epileptiform field potential repetition rate, amplitude and integral were compared between slices containing a cortical freeze lesion, and slices from sham-operated rats. No interictal spikes and no electrographic or clinical seizures occurred in either group. The median threshold for pentylenetetrazol-induced seizures was 60 mg/kg for lesioned, and 45 mg/kg for control animals (difference not significant). No spontaneous epileptiform field potentials were recorded from either freeze-lesion or control slices bathed in normal, artificial cerebrospinal fluid (ACSF). Upon omission of Mg(2+) from the bath, epileptiform field potentials were elicited that showed a significantly higher burst integral in the freeze lesion slices compared to control slices. Neocortical freeze lesions induced in newborn rat pups show histological characteristics reminiscent of human cortical dysplasia. Brain slices containing neocortical freeze lesions display hyperexcitability in vitro, but the same lesion does not appear to show spontaneous epileptogenicity in vivo.
Journal of Pharmacological and Toxicological Methods, 2008
Journal of Neurology, Neurosurgery & Psychiatry, 2009
The purpose of this study was to investigate the safety and efficacy of intravenous levetiracetam... more The purpose of this study was to investigate the safety and efficacy of intravenous levetiracetam (LEV-iv) in refractory status epilepticus (SE). A retrospective chart review was performed on patients who received LEV-iv for treatment of SE (n = 36) and had failed at least one other antiepileptic drug. LEV-iv (median 3000 mg/day; range 1000-9000) was administered as a bolus loading (500-2000 mg per 30-60 min, n = 30) or as a continuous pump infusion (n = 6). SE was terminated in 69% ("responders"); 31% ("non-responders") remained in SE. Factors associated with failure were: dose escalation over 3000 mg/day, lack of bolus loading, treatment latency over 48 h, age over 80 years, non-convulsive SE with coma ("subtle SE"), periodic lateralised epileptiform discharges (PLEDs) on EEG, acute cerebral lesion and intubation narcosis. SE was terminated in all eight patients without brain lesion (p = 0.033), and in all seven patients with complex partial SE (p = 0.051). Outcome was favourable (ambulatory patients) in 48% (responders) compared with 0% (non-responders), and "adverse" (death or continuing coma/stupor) in 24% (responders) compared with 100% (non-responders). Mortality was 17% (responders 4%, non-responders 45%). No patient had cardiocirculatory side effects or worsening of SE. Two patients experienced nausea and vomiting during LEV-iv loading, leading to aspiration pneumonia in one. This study suggests that LEV-iv may be a safe and efficacious treatment of SE. Prospective and controlled trials are imperative to confirm these preliminary findings.
Epilepsy & Behavior, 2008
Objective. The intracarotid amobarbital procedure (IAP) is routinely used in the preoperative wor... more Objective. The intracarotid amobarbital procedure (IAP) is routinely used in the preoperative workup of patients with epilepsy. We previously reported dissections and seizures as complications of this procedure and now have reviewed our cohort for additional complications associated with the IAP. Methods. Charts of 677 consecutive patients were reviewed for complications during the IAP. Results. Complications were observed in 74 patients (10.9%) and included encephalopathy (7.2%), seizures (1.2%), strokes (0.6%), transient ischemic attacks (0.6%), localized hemorrhage at the catheter insertion site (0.6%), carotid artery dissections (0.4%), allergic reaction to contrast (0.3%), bleeding from the catheter insertion site (0.1%), and infection (0.1%). Older patients were more prone to strokes and dissections, whereas younger patients more frequently experienced seizures. Use of amobarbital was associated with encephalopathy, whereas methohexital was related to seizures. Conclusion. The IAP bears the risk of minor and major complications in up to 11% of patients. Risks, benefits, and possible alternative options have to be considered when a patient is to undergo the IAP.
Epilepsy & Behavior, 2007
Background. Methohexital and amobarbital have been used as agents for Wada testing in the presurg... more Background. Methohexital and amobarbital have been used as agents for Wada testing in the presurgical evaluation of patients with epilepsy. Previous experience with methohexital as an anesthetic indicates that methohexital may decrease seizure threshold and may trigger seizures. Methods. A retrospective chart review of 760 intracarotid amobarbital and methohexital tests was performed to determine the frequency of seizures associated with preoperative intracarotid barbiturate testing for language and memory lateralization. Results. Sixteen patients (2.1%) who had seizures were found. In 3 patients, seizures occurred prior to barbiturate injection, and in 13, following barbiturate injection. After injection of amobarbital, 4 of 538 patients (0.7%) had a seizure. Nine of 222 patients had a seizure after methohexital injection (4.1%) (P = 0.001). Conclusion. Patients with a previous history of epilepsy may be at higher risk for seizures after methohexital injection as compared with amobarbital injection.
Therapie-Handbuch Grundwerk inkl 6. Lfg., 2007
Purpose To characterize the interaction between language dominance and lateralization of the epil... more Purpose To characterize the interaction between language dominance and lateralization of the epileptic focus for pre- and postoperative Boston Naming Test (BNT) performance in patients undergoing anterior temporal lobectomy (ATL). Methods Analysis of pre- and postoperative BNT scores depending on lateralization of language as measured by the intracarotid amobarbital procedure (IAP) versus lateralization of the temporal lobe epileptic focus. Results Changes between pre- and postoperative BNT performance depended on epilepsy lateralization (effect size = 0.189) with significant decrease in patients undergoing left ATL. Subgroup analysis in these showed that postoperative decline in BNT scores was significant in patients with atypical (n = 14; p <
The recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-... more The recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-oriented approach. Epilepsy syndromes--at least as defined by the ILAE Task Force--group patients according to multiple, usually poorly defined parameters. As a result, these syndromes frequently show significant overlap and may change with patient age. We propose a five-dimensional and patient-oriented approach to epilepsy classification. This approach shifts away from syndrome orientation, using independent criteria in each of the five dimensions similarly to the diagnostic process in general neurology. The main dimensions of this new classification consist of (1) localizing the epileptogenic zone, (2) semiology of the seizure, (3) etiology, (4) seizure frequency, and (5) related medical conditions. These dimensions characterize all information necessary for patient management, are independent parameters, and include information more pertinent than the ILAE axes with regard to patient ...
Klinische Neurophysiologie, 2016
Clinical Neurophysiology, 2015
Clinical Neurophysiology, 2015
Triphasic waves are commonly seen in the EEG of patients with encephalopathy. Although typically ... more Triphasic waves are commonly seen in the EEG of patients with encephalopathy. Although typically associated with metabolic encephalopathy or post-hypoxic damage, they are unspecific in respect of the etiology of brain dysfunction. Here, we present a case report of acute-onset triphasic waves induced by hypercapnia. We report on a 27-year-old male with severe sensory and motor neuropathy, tetraparesis, ataxia, dysarthria, and cognitive impairment of yet unknown etiology since the age of 14 years. The patient was referred to our hospital and admitted to the EEG monitoring unit for differential diagnosis of recurrent episodes of loss of consciousness. At time of admission, a borderline oxygen saturation (SatO2) of around 80% was recorded, attributable to his chronic neuromuscular disease. During the first evening after admission, SatO2 repeatedly dropped below 80%. Oxygen insufflation was initiated by the doctor-on-call and the patient’s vigilance was repeatedly tested throughout the night. At a routine check, the patient was found stuporous. Blood gas analysis showed carbon dioxide partial pressure (pCO2) of 85.6 mmHg and oxygen partial pressure (pO2) of 75.6 mmHg. Emergency bag-valve mask ventilation was started, the patient was intubated, and transferred to the intensive care unit. After several days, the patient was extubated without any new-onset neurological deficit. Polysomnography revealed alveolar hypoventilation, and non-invasive assisted bilevel ventilation treatment was initiated before the patient was discharged home. Upon post hoc review, the EEG during the night after admission showed normal sleep patterns which were replaced by triphasic waves just about 10 min before the patient was found to be stuporous. Upon bag-valve-mask ventilation, the triphasic waves disappeared within 2–3 min, and the EEG showed a normal awake state prior to sedation intubation. This case demonstrates that hypercapnia may induce acute-onset triphasic waves in the EEG which are readily reversible within minutes after assisted ventilation. Moreover, this case illustrates the danger of oxygen insufflation in patients with chronic alveolar hypoventilation. We conclude that our patient suffered from chronic alveolar hypoventilation due to severe neuropathy which resulted in chronic moderate hypercapnia, with respiration triggered by hypoxia alone. When receiving oxygen insufflation, hypoxia-induced respiration failed leading to central hypopnea, acute pCO2 increase and stupor.
Der Nervenarzt
Neurostimulation techniques are applied to reduce the frequency and severity of epileptic seizure... more Neurostimulation techniques are applied to reduce the frequency and severity of epileptic seizures. Class I evidence showed that vagus nerve stimulation (VNS) reduces seizure burden by 25-28% compared to 6-15% in placebo controls. Open-label studies, however, reported much greater efficacy. Since 2010 deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is CE approved for epilepsy therapy in Europe. A multicenter randomized controlled trial reported seizure frequency reduction by 40.4% compared to 14.5% in controls. A significant effect was only found in patients with temporal seizure onset. 13% of stimulated patients became seizure-free for at least 6 months. Possible side-effects include depression (14.8%) and memory impairment (13%). Responsive neurostimulation (RNS) combines an automated seizure detection device with on-demand triggered stimulation of the epileptogenic zone. A randomized controlled trial reported seizure frequency reduction by 37.9% compared to 17.3% in controls. There were no relevant neuropsychological or psychiatric side-effects noted.
Der Nervenarzt
Der Status epilepticus (SE) gehört mit einer jährlichen Inzidenz von 10–20/100.000 Einwohnern zu ... more Der Status epilepticus (SE) gehört mit einer jährlichen Inzidenz von 10–20/100.000 Einwohnern zu den häufigsten Notfällen in der Neurologie. Die Gesamtmortalität liegt abhängig von einer Reihe klinischer Parameter zwischen 10% und 20%. Die Patienten zeigen lang andauernde oder in Serie auftretende motorische Anfälle oder prolongierte Bewusstseinsstörungen bis hin zum Koma. Darüber hinaus können eine Reihe systemischer Komplikationen auftreten, die auch als Folge einer aggressiven medikamentösen Therapie möglich sind. Während sich der überwiegende Teil der SE durch standardisierte Behandlungsalgorithmen unterbrechen lässt, erweisen sich einige SE als refraktär gegen diese Initialtherapie und bedürfen einer intensivmedizinischen Intervention. Hier kommen vornehmlich nicht sedierende Antikonvulsiva und bei Bedarf zusätzlich Injektionsnarkotika zum Einsatz. In Einzelfällen stellen nichtmedikamentöse Therapieansätze (z. B. die Epilepsiechirurgie) eine zusätzliche Behandlungsalternative d...
Therapie-Handbuch Grundwerk inkl 6. Lfg., 2015
Der Nervenarzt, 2003
Attempts to control epileptic seizures by electrical brain stimulation have been performed for 50... more Attempts to control epileptic seizures by electrical brain stimulation have been performed for 50 years. Many different stimulation targets and methods have been investigated. Vagal nerve stimulation (VNS) is now approved for the treatment of refractory epilepsies by several governmental authorities in Europe and North America. However, it is mainly used as a palliative method when patients do not respond to medical treatment and epilepsy surgery is not possible. Numerous studies of the effect of deep brain stimulation (DBS) on epileptic seizures have been performed and almost invariably report remarkable success. However, a limited number of controlled studies failed to show a significant effect. Repetitive transcranial magnetic stimulation (rTMS) also was effective in open studies, and controlled studies are now being carried out. In addition, several uncontrolled reports describe successful treatment of refractory status epilepticus with electroconvulsive therapy (ECT). In summar...
Aktuelle Neurologie, 2014
Parasomnien umfassen eine grose Gruppe unterschiedlicher motorischer Phanomene wahrend des Schlaf... more Parasomnien umfassen eine grose Gruppe unterschiedlicher motorischer Phanomene wahrend des Schlafes. Entsprechend der Internationalen Klassifikation von Schlafstorungen II (ICSD II) werden Parasomnien in Formen unterteilt, die aus dem Non-REM-Schlaf heraus auftreten und Formen, die aus dem REM-Schlaf auftreten. Als andere Parasomnien werden die Formen bezeichnet, bei denen keine feste Zuordnung zu einem Schlafstadium moglich ist. Schlafwandeln, Schlaftrunkenheit und der Pavor nocturnus sind die klinisch wichtigsten Formen der Non-REM Parasomnien. Hauptmerkmal dieser Formen ist der Beginn aus dem Schlafstadium Non-REM 3, dem durch hohen Anteil an Deltaaktivitat gekennzeichneten Tiefschlaf. Die Gesamtpravalenz der Non-REM-Parasomnien bei Erwachsenen wird mit ca. 4% angegeben. Damit ist diese Form der Parasomnien eine klinisch relevante, aber vermutlich unterdiagnostizierte Gruppe von Schlafstorungen. Als besondere Form der Parasomnie gilt neben den Non-REM-Parasomnien die schlafbezogene Essstorung. Diese in die Gruppe der anderen Parasomnien klassifizierte Schlafstorung tritt aus Non-REM-Stadium 2 und 3 auf. Fur alle hier beschriebenen Parasomnien gilt, dass assoziierte Symptome wie Tagesschlafrigkeit, Traumerinnern und nachtliche autonome Aktivierungen haufiger zu finden sind als allgemein angenommen wurde. Die wichtigsten Differenzialdiagnosen des Schlafwandelns und der gesamten Gruppe der Non-REM-Parasomnien sind die REM-Schlaf-assoziierten Parasomnien, wie die REM-Schlaf-Verhaltensstorung und epileptische Anfalle aus dem Schlaf, bspw. bei Patienten mit nachtlicher Frontallappenepilepsie. Da die nachtlichen, motorischen Symptome keine ausreichende und sichere Differenzierung der verschiedenen Differenzialdiagnosen zulassen, stellt die videobasierte Polysomnografie im Schlaflabor den Gold-Standard in der technischen Diagnosestellung dar. Ebenso dient die videobasierte Polysomnografie der Entscheidung zur erweiterten video-basierten elektroenzephalografischen Diagnostik. Vor diesem Hintergrund ist fur die Diagnosestellung von Schlafwandeln und Non-REM-Parasomnien die enge Zusammenarbeit zwischen Schlafmedizinern und Epileptologen empfehlenswert.
Chemokines, a family member of cytokines, have been shown to play a major role in central nervous... more Chemokines, a family member of cytokines, have been shown to play a major role in central nervous system inflammation. Among other chemokines, CXCR3 and its ligand CXCL10 are involved in the pathophysiology of several neuroinflammatory conditions. Most of these conditions are also associated with an increased incidence of seizure or epilepsy. Using age-matched wild-type (WT), as well as CXCR3-receptor-deficient (CXCR3-KO) mice, the present study aimed to investigate the effect of the chemokine CXCL10 and its receptor CXCR3 on synaptic plasticity as well as neuronal activities in hippocampal brain slices. Using field potential and intracellular recordings, the effect of exogenous CXCL10 on tetanus-induced long-term potentiation (LTP) as well as the neuronal spike activity was evaluated in hippocampal CA1 area. Exogenous application of CXCL10 enhanced LTP in WT mice, whereas it exerted no significant effect on CXCR3-KO mice. During intracellular recordings of spontaneous spike activity, exogenous application of CXCL10 significantly enhanced the amplitude, duration, and after-hyperpolarization of action potentials in slices obtained from WT mice compared to CXCR3-KO mice. In addition, CXCR3-KO mice exhibited a lower GABAA-mediated excitation in hippocampal CA1 neurons compared to WT mice. These data show that the inflammatory chemokine CXCL10, probably via its receptor CXCR3, modulates neuronal activity and synaptic plasticity in the hippocampus. CXCL10 may be involved in seizures observed during neuroinflammatory diseases such as meningitis and encephalitis.
Epileptic disorders, 2007
Malformations of cortical development are frequent causes of human refractory epilepsy. The freez... more Malformations of cortical development are frequent causes of human refractory epilepsy. The freeze-lesion model in rats shows histopathological features similar to those found in human polymicrogyria. Previous studies reported in vitro hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed. Neocortical freeze lesions were induced in Sprague-Dawley rat pups (n = 10) on postnatal day 0 or 1 (P0/P1). Sham-operated animals served as controls (n = 10). On P60, animals were implanted with epidural electrodes for long-term video-EEG monitoring (4 weeks). The threshold for pentylenetetrazol-induced seizures was determined. Animals were sacrificed and brain sections processed for histological staining and in vitro electrophysiological recordings. Epileptiform field potential repetition rate, amplitude and integral were compared between slices containing a cortical freeze lesion, and slices from sham-operated rats. No interictal spikes and no electrographic or clinical seizures occurred in either group. The median threshold for pentylenetetrazol-induced seizures was 60 mg/kg for lesioned, and 45 mg/kg for control animals (difference not significant). No spontaneous epileptiform field potentials were recorded from either freeze-lesion or control slices bathed in normal, artificial cerebrospinal fluid (ACSF). Upon omission of Mg(2+) from the bath, epileptiform field potentials were elicited that showed a significantly higher burst integral in the freeze lesion slices compared to control slices. Neocortical freeze lesions induced in newborn rat pups show histological characteristics reminiscent of human cortical dysplasia. Brain slices containing neocortical freeze lesions display hyperexcitability in vitro, but the same lesion does not appear to show spontaneous epileptogenicity in vivo.
Journal of Pharmacological and Toxicological Methods, 2008
Journal of Neurology, Neurosurgery & Psychiatry, 2009
The purpose of this study was to investigate the safety and efficacy of intravenous levetiracetam... more The purpose of this study was to investigate the safety and efficacy of intravenous levetiracetam (LEV-iv) in refractory status epilepticus (SE). A retrospective chart review was performed on patients who received LEV-iv for treatment of SE (n = 36) and had failed at least one other antiepileptic drug. LEV-iv (median 3000 mg/day; range 1000-9000) was administered as a bolus loading (500-2000 mg per 30-60 min, n = 30) or as a continuous pump infusion (n = 6). SE was terminated in 69% ("responders"); 31% ("non-responders") remained in SE. Factors associated with failure were: dose escalation over 3000 mg/day, lack of bolus loading, treatment latency over 48 h, age over 80 years, non-convulsive SE with coma ("subtle SE"), periodic lateralised epileptiform discharges (PLEDs) on EEG, acute cerebral lesion and intubation narcosis. SE was terminated in all eight patients without brain lesion (p = 0.033), and in all seven patients with complex partial SE (p = 0.051). Outcome was favourable (ambulatory patients) in 48% (responders) compared with 0% (non-responders), and "adverse" (death or continuing coma/stupor) in 24% (responders) compared with 100% (non-responders). Mortality was 17% (responders 4%, non-responders 45%). No patient had cardiocirculatory side effects or worsening of SE. Two patients experienced nausea and vomiting during LEV-iv loading, leading to aspiration pneumonia in one. This study suggests that LEV-iv may be a safe and efficacious treatment of SE. Prospective and controlled trials are imperative to confirm these preliminary findings.
Epilepsy & Behavior, 2008
Objective. The intracarotid amobarbital procedure (IAP) is routinely used in the preoperative wor... more Objective. The intracarotid amobarbital procedure (IAP) is routinely used in the preoperative workup of patients with epilepsy. We previously reported dissections and seizures as complications of this procedure and now have reviewed our cohort for additional complications associated with the IAP. Methods. Charts of 677 consecutive patients were reviewed for complications during the IAP. Results. Complications were observed in 74 patients (10.9%) and included encephalopathy (7.2%), seizures (1.2%), strokes (0.6%), transient ischemic attacks (0.6%), localized hemorrhage at the catheter insertion site (0.6%), carotid artery dissections (0.4%), allergic reaction to contrast (0.3%), bleeding from the catheter insertion site (0.1%), and infection (0.1%). Older patients were more prone to strokes and dissections, whereas younger patients more frequently experienced seizures. Use of amobarbital was associated with encephalopathy, whereas methohexital was related to seizures. Conclusion. The IAP bears the risk of minor and major complications in up to 11% of patients. Risks, benefits, and possible alternative options have to be considered when a patient is to undergo the IAP.
Epilepsy & Behavior, 2007
Background. Methohexital and amobarbital have been used as agents for Wada testing in the presurg... more Background. Methohexital and amobarbital have been used as agents for Wada testing in the presurgical evaluation of patients with epilepsy. Previous experience with methohexital as an anesthetic indicates that methohexital may decrease seizure threshold and may trigger seizures. Methods. A retrospective chart review of 760 intracarotid amobarbital and methohexital tests was performed to determine the frequency of seizures associated with preoperative intracarotid barbiturate testing for language and memory lateralization. Results. Sixteen patients (2.1%) who had seizures were found. In 3 patients, seizures occurred prior to barbiturate injection, and in 13, following barbiturate injection. After injection of amobarbital, 4 of 538 patients (0.7%) had a seizure. Nine of 222 patients had a seizure after methohexital injection (4.1%) (P = 0.001). Conclusion. Patients with a previous history of epilepsy may be at higher risk for seizures after methohexital injection as compared with amobarbital injection.