Phenobarbital in super-refractory status epilepticus (PIRATE): A retrospective, multicenter analysis.

OBJECTIVE: Super-refractory status epilepticus (SRSE) is an enduring or recurring SE after 24 h or more of general anesthesia. This study aimed to evaluate the efficacy and safety of phenobarbital (PB) for the treatment of SRSE. METHODS: This retrospective, multicenter study included neurointensive care unit (NICU) patients with SRSE treated with PB between September 2015 and September 2020 from six participating centers of the Initiative of German NeuroIntensive Trial Engagement (IGNITE) to evaluate the efficacy and safety of PB treatment for SRSE. The primary outcome measure was seizure termination. In addition, we evaluated maximum reached serum levels, treatment duration, and clinical complications using a multivariate generalized linear model. RESULTS: Ninety-one patients were included (45.1% female). Seizure termination was achieved in 54 patients (59.3%). Increasing serum levels of PB were associated with successful seizure control (per µg/mL: adjusted odds ratio [adj.OR] = 1.1, 95% confidence interval [CI] 1.0-1.2, p < .01). The median length of treatment in the NICU was 33.7 [23.2-56.6] days across groups. Clinical complications occurred in 89% (n = 81) of patients and included ICU-acquired infections, hypotension requiring catecholamine therapy, and anaphylactic shock. There was no association between clinical complications and treatment outcome or in-hospital mortality. The overall average modified Rankin scale (mRS) at discharge from the NICU was 5 ± 1. Six patients (6.6%) reached mRS ≤3, of whom five were successfully treated with PB. In-hospital mortality was significantly higher in patients in whom seizure control could not be achieved. SIGNIFICANCE: We observed a high rate in attainment of seizure control in patients treated with PB. Success of treatment correlated with higher dosing and serum levels. However, as one would expect in a cohort of critically ill patients with prolonged NICU treatment, the rate of favorable clinical outcome at discharge from the NICU remained extremely low. Further prospective studies evaluating long-term clinical outcome of PB treatment as well as an earlier use of PB at higher doses would be of value.

Isoflurane in (Super-) Refractory Status Epilepticus: A Multicenter Evaluation.

BACKGROUND: We aimed to determine the association between seizure termination and side effects of isoflurane for the treatment of refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) in neurointensive care units (neuro-ICUs). METHODS: This was a multicenter retrospective study of patients with RSE/SRSE treated with isoflurane for status epilepticus termination admitted to the neuro-ICUs of nine German university centers during 2011-2018. RESULTS: We identified 45 patients who received isoflurane for the treatment of RSE/SRSE. During isoflurane treatment, electroencephalograms showed no epileptiform discharges in 33 of 41 (80%) patients, and burst suppression pattern was achieved in 29 of 41 patients (71%). RSE/SRSE was finally terminated after treatment with isoflurane in 23 of 45 patients (51%) for the entire group and in 13 of 45 patients (29%) without additional therapy. Lengths of stay in the hospital and in the neuro-ICU were significantly extended in cases of ongoing status epilepticus under isoflurane treatment (p = 0.01 for length of stay in the hospital, p = 0.049 for length in the neuro-ICU). During isoflurane treatment, side effects were reported in 40 of 45 patients (89%) and mainly included hypotension (n = 40, 89%) and/or infection (n = 20, 44%). Whether side effects occurred did not affect the outcome at discharge. Of 22 patients with follow-up magnetic resonance imaging, 2 patients (9%) showed progressive magnetic resonance imaging alterations that were considered to be potentially associated with RSE/SRSE itself or with isoflurane therapy. CONCLUSIONS: Isoflurane was associated with a good effect in stopping RSE/SRSE. Nevertheless, establishing remission remained difficult. Side effects were common but without effect on the outcome at discharge.

[Narcolepsy in adults: Definition, etiology and treatment]. / Narkolepsie im Erwachsenenalter: Definition, Ätiologie und Behandlung.

Narcolepsy is a hypersomnolence disorder of central origin that presents with a disturbance of the wake-sleep regulation. Lead symptoms consist of excessive daytime sleepiness and cataplexy. Nowadays, two types of narcolepsy are distinguished. Type 1 narcolepsy, formerly known as narcolepsy with cataplexy, is based on hypocretin deficiency. The cause of type 2 narcolepsy, formerly known as narcolepsy without cataplexy, remains mainly unknown. A multimodal approach is necessary for diagnosis. The mean latency between the onset of disease and diagnosis in Europe ranges 14 years. Narcolepsy has a major impact on workability and quality of life. The management of narcolepsy is usually life-long and includes non-pharmacological approaches and a symptomatic pharmacological treatment.

Can commercially available wearable EEG devices be used for diagnostic purposes? An explorative pilot study.

Electroencephalography (EEG) is a core element in the diagnosis of epilepsy syndromes and can help to monitor antiseizure treatment. Mobile EEG (mEEG) devices are increasingly available on the consumer market and may offer easier access to EEG recordings especially in rural or resource-poor areas. The usefulness of consumer-grade devices for clinical purposes is still underinvestigated. Here, we compared EEG traces of a commercially available mEEG device (Emotiv EPOC) to a simultaneously recorded clinical video EEG (vEEG). Twenty-two adult patients (11 female, mean age 40.2 years) undergoing noninvasive vEEG monitoring for clinical purposes were prospectively enrolled. The EEG recordings were evaluated by 10 independent raters with unmodifiable view settings. The individual evaluations were compared with respect to the presence of abnormal EEG findings (regional slowing, epileptiform potentials, seizure pattern). Video EEG yielded a sensitivity of 56% and specificity of 88% for abnormal EEG findings, whereas mEEG reached 39% and 85%, respectively. Interrater reliability coefficients were better in vEEG as compared to mEEG (ϰ = 0.50 vs. 0.30), corresponding to a moderate and fair agreement. Intrarater reliability between mEEG and vEEG evaluations of simultaneous recordings of a given participant was moderate (ϰ = 0.48). Given the limitations of our exploratory pilot study, our results suggest that vEEG is superior to mEEG, but that mEEG can be helpful for diagnostic purposes. We present the first quantitative comparison of simultaneously acquired clinical and mobile consumer-grade EEG for a clinical use-case.

[Status epilepticus]. / Status epilepticus.

Status epilepticus is a neurologic emergency manifested by prolonged seizure activity or multiple seizures without full recovery of previous condition in between. The most important aim of treatment is early seizure termination, because duration of status epilepticus correlates with a higher rate of morbidity and mortality. Based on evidence from clinical trials and guidelines strategies for management of status epilepticus are provided.

Suspected new-onset autoimmune temporal lobe epilepsy with amygdala enlargement.

OBJECTIVE: Recent reports define temporal lobe epilepsy with amygdala enlargement (TLE-AE) as a distinct electroclinical syndrome comparable to TLE with hippocampal sclerosis. In this retrospective observational study, we present the largest consecutive series of patients with new-onset TLE-AE to date and describe clinical characteristics and seizure outcome, and we aim to explore underlying autoimmune mechanisms within this syndrome. METHODS: We reviewed all consecutive patients between 2004 and 2014 at our tertiary epilepsy center at the University of Bonn, Germany, with new-onset (<5 years) TLE-AE, negative serum antibody (ab) test results, and with available follow-up data for at least 12 months. RESULTS: We identified 40 patients (23 male) with TLE-AE with a median age at epilepsy onset of 51 years (range 10-73) and a median disease duration of 11 months (range 0.5-55) at first presentation. At follow-up, 50% of the entire cohort achieved seizure freedom. Of interest, patients with remittent features of AE at follow-up (N = 24) had a superior outcome compared to those with stable magnetic resonance imaging (MRI) features of AE (N = 16): 17 (71%) of 24 were seizure-free for at least 6 months compared to 3 (19%) of 16, respectively (p = 0.003). MRI volumetry confirmed significantly enlarged amygdalae in TLE-AE in relation to healthy controls, and additionally showed significantly greater volume reductions in patients with remittent AE compared to those with stable AE. SIGNIFICANCE: TLE-AE is a clinical syndrome beginning mostly in middle age, and in addition to its known association with ab-positive limbic encephalitis, it occurs in an ab-negative condition. Remission of AE in the course of the disease could be identified as a predictor for a favorable clinical outcome and is suspicious of an autoimmune etiology, although we could not confirm this hypothesis unequivocally with currently available noninvasive diagnostic tools.

Distinct white matter integrity in glutamic acid decarboxylase and voltage-gated potassium channel-complex antibody-associated limbic encephalitis.

OBJECTIVE: Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage-gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI). METHODS: Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC-complex antibodies and compared with age- and gender-matched control groups. Voxelwise statistical analysis was carried out using tract-based spatial statistics. The results were furthermore compared with those of 15 patients with unilateral histologically confirmed hippocampal sclerosis and correlated with verbal and figural memory performance. RESULTS: We found widespread changes of fractional anisotropy and all diffusivity parameters in GAD-associated limbic encephalitis, whereas no changes were found in VGKC-complex-associated limbic encephalitis. The changes observed in the GAD group were even more extensive when compared against those of the hippocampal sclerosis group, although the disease duration was markedly shorter in patients with GAD antibodies. Correlation analysis revealed areas with a trend toward a negative correlation of diffusivity parameters with figural memory performance located mainly in the right temporal lobe in the GAD group as well. SIGNIFICANCE: The present study provides further evidence that, depending on the associated antibody, limbic encephalitis features clearly distinct imaging characteristics by showing widespread white matter changes in GAD-associated limbic encephalitis and preserved white matter integrity in VGKC-complex-associated limbic encephalitis. Furthermore, our results contribute to a better understanding of the specific pathophysiologic properties in these two subforms of limbic encephalitis by revealing that patients with GAD antibodies show widespread affections of white matter across various regions of the brain. In contrast to this, the inflammatory process seems to be more localized in VGKC-complex-associated limbic encephalitis, primarily affecting mesiotemporal gray matter.

Automated volumetry of the mesiotemporal structures in antibody-associated limbic encephalitis.

OBJECTIVE: Limbic encephalitis (LE) is an autoimmune mediated disease leading to temporal lobe epilepsy, mnestic and psychiatric symptoms. In recent years, several LE subforms defined by serum antibody findings have been described. MRI usually shows volume changes of the amygdala and hippocampus. However, studies quantifying longitudinal volume changes in the acute disease stage are lacking. METHODS: The aim of this retrospective observational study was to evaluate and quantify these volume changes by applying a fully automated volumetric approach to serial MRIs of 28 patients with antibody-associated LE. The results were compared with those of 28 age-matched and gender-matched healthy controls and analysed separately for the different antibody profiles and correlated with clinical parameters. Antibody profile analyses were exploratory due to the relatively small sample sizes. RESULTS: We found distinct volumetric and clinical courses depending on the associated antibody. While LE associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) showed highly significant larger volumes of both the amygdala and the hippocampus within the first 12 months after disease onset, LE associated with glutamic acid decarboxylase antibodies (GAD-LE) only displayed greater amygdala volumes at this disease stage. Both subgroups showed a reduction of the amygdala and hippocampus volumes during follow-up with higher volume changes in VGKC-LE. CONCLUSIONS: These differences in the volumetric evolution corresponded to distinct clinical courses in terms of a more severe initial symptomatology regarding seizure, mnestic and psychiatric disturbances in VGKC-LE, which improved rapidly, corresponding to the evolution of the volumetric changes. In contrast to this, patients with GAD-LE were less severely affected at disease onset, showing a more unmodulated and chronic disease course during follow-up.

Different pain phenotypes are associated with anti-Caspr2 autoantibodies.

Autoantibodies against contactin-associated protein 2 (Caspr2) not only induce limbic autoimmune encephalitis but are also associated with pain conditions. Here, we analyzed clinical data on pain in a large cohort of patients included into the German Network for Research in Autoimmune Encephalitis. Out of 102 patients in our cohort, pain was a frequent symptom (36% of all patients), often severe (63.6% of the patients with pain) and/or even the major symptom (55.6% of the patients with pain). Pain phenotypes differed between patients. Cluster analysis revealed two major phenotypes including mostly distal-symmetric burning pain and widespread pain with myalgia and cramps. Almost all patients had IgG4 autoantibodies and some additional IgG1, 2, and/or 3 autoantibodies, but IgG subclasses, titers, and presence or absence of intrathecal synthesis were not associated with the occurrence of pain. However, certain pre-existing risk factors for chronic pain like diabetes mellitus, peripheral neuropathy, or preexisting chronic back pain tended to occur more frequently in patients with anti-Caspr2 autoantibodies and pain. Our data show that pain is a relevant symptom in patients with anti-Caspr2 autoantibodies and support the idea of decreased algesic thresholds leading to pain. Testing for anti-Caspr2 autoantibodies needs to be considered in patients with various pain phenotypes.

Surgical management and long-term seizure outcome after epilepsy surgery for different types of epilepsy associated with cerebral cavernous malformations.

PURPOSE: Precise outcome data about the surgical therapy of cerebral cavernous malformation (CCM)-associated epilepsy is scarce regarding different epilepsy types, surgical approach, and outcome. Long-term outcome in patients with CCM-associated epilepsy is analyzed in a large single-center series. METHODS: Seizure outcome data >24 months was available in 118 patients. The influence of different parameters of preoperative workup and surgical technique was analyzed with regard to seizure outcome. KEY FINDINGS: The study cohort comprised 76 patients with drug-resistant epilepsy (DRE), 20 patients with chronic epilepsy that did not meet the definition of DRE, as well as 22 patients with sporadic seizures. Temporal localization of CCMs predisposed to develop DRE. Detailed epileptologic workup was performed in 85 patients; invasive monitoring was done in 23 (37%) of 76 DRE cases. In 84% of DRE cases more extensive resections were performed. Mean follow-up varied between 107 and 137 months for the three groups. Seizure freedom in DRE was 88%, in chronic epilepsy 80%, and in sporadic seizures was 91%. Longer symptom duration was associated with worse seizure outcome. Outcome of patients who underwent invasive monitoring was not worse. The outcome in CCM-associated DRE can be good if more extensive resections are used and if noninvasive and/or invasive presurgical epileptologic workup is used whenever indicated. DRE was considerably more frequent in the temporal lobe, suggesting that temporal localization predisposes development of DRE. Seizure freedom rates were stable over a long period. SIGNIFICANCE: Surgical therapy of CCM-associated seizures and epilepsy can be successful if different surgical techniques according to presurgical evaluation are realized. To prevent clinical worsening into DRE, surgical intervention in CCM-associated epilepsy may be considered early.

Quantitative FLAIR analysis indicates predominant affection of the amygdala in antibody-associated limbic encephalitis.

PURPOSE: Limbic encephalitis is an autoimmune-mediated disease leading to temporal lobe epilepsy, mnestic deficits, and affective disturbances. Magnetic resonance imaging (MRI) usually shows signal and volume changes of the temporomesial structures. However, these abnormalities may be subtle, thereby hampering the diagnosis by conventional visual assessment. In the present study we evaluated the diagnostic value of a fully automated MRI postprocessing technique in limbic encephalitis and hippocampal sclerosis. METHODS: The MRI postprocessing was based largely on a recently described method allowing for an observer-independent quantification of the fluid-attenuated inversion recovery (FLAIR) signal intensities of amygdala and hippocampus. A 95% confidence region was calculated from the FLAIR intensities of 100 healthy controls. We applied this analysis to the MRI data of 39 patients with antibody-associated limbic encephalitis and 63 patients with hippocampal sclerosis. Moreover, the results were compared to those of visual assessment by an experienced neuroradiologist. KEY FINDINGS: The method detected limbic encephalitis and hippocampal sclerosis with a high sensitivity of 85% and 95%, respectively. The detection rate of the automated approach in limbic encephalitis was significantly superior to visual analysis (85% vs. 51%; p = 0.001), whereas no statistically significant difference for the detection rate in hippocampal sclerosis was found. Patients with limbic encephalitis had significantly higher absolute intensity values of the amygdala and a significantly higher percentage fell outside of the amygdalar confidence region compared to those with hippocampal sclerosis (79% vs. 27%; p < 0.001), whereas we found opposite results in the hippocampal analysis (38% vs. 95%; p < 0.001). SIGNIFICANCE: The FLAIR analysis applied in this study is a powerful tool to quantify signal changes of the amygdala and hippocampus in limbic encephalitis and hippocampal sclerosis. It significantly increases the diagnostic sensitivity in limbic encephalitis in comparison to conventional visual analysis. Furthermore, the method provides an interesting insight into the distinct properties of these two disease entities on MRI, indicating a predominant affection of the amygdala in limbic encephalitis, whereas the affection of the hippocampus is far less pronounced when compared to hippocampal sclerosis.

Seizures at stroke onset: A case-control study.

PURPOSE: Seizures occurring at the immediate onset of a stroke, abbreviated "seizures at onset" (SaO), pose a diagnostic and therapeutic challenge for physicians. In this study, we report on the current clinical practice in managing stroke patients with SaO from a large tertiary stroke center in Germany. METHODS: We selected all patients with SaO and acute ischemic or hemorrhagic stroke admitted to the Department of Neurology at the University Hospital of Cologne between 2019 and 01-01 and 2020-12-31. SaO patients were then compared to patients with acute ischemic or hemorrhagic stroke without SaO from the local stroke registry. Further, we compared SaO patients who received intravenous recombinant tissue-type plasminogen activator (rt-PA) and/or mechanical thrombectomy with matched controls. RESULTS: Overall, 54 out of 2312 stroke patients (2.3 %) in the examined period presented with SaO. The most prevalent SaO semiology was focal to bilateral tonic-clonic (42.6 %). SaO was associated with hemorrhagic strokes and higher in-hospital mortality in all stroke patients. The rate of acute stroke therapy was not influenced by the occurrence of SaO. In patients that received acute stroke therapy, patients with SaO had higher scores on the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) at admission, and longer door-to-needle times for the administration of rt-PA, while none of the examined outcome parameters revealed a difference between patients with and without SaO after adjusting for potential confounders. CONCLUSION: Data show that SaO is rare in stroke patients but associated with more extensive strokes.

Prehospital Levetiracetam Use in Adults With Status Epilepticus: Results of a Multicenter Registry.

BACKGROUND AND PURPOSE: Status epilepticus (SE) is a neurological emergency due to prolonged seizure activity or multiple seizures without full recovery in between them. Prehospital SE management is crucial since its duration is correlated with higher morbidity and mortality rates. We examined the impact of different therapeutic strategies in the prehospital setting with a focus on levetiracetam. METHODS: We initiated the Project for SE in Cologne, a scientific association of all neurological departments of Cologne, the fourth-largest city in Germany with around 1,000,000 inhabitants. All patients with an SE diagnosis were evaluated over 2 years (from March 2019 to February 2021) to determine whether prehospital levetiracetam use had a significant effect on SE parameters. RESULTS: We identified 145 patients who received initial drug therapy in the prehospital setting by professional medical staff. Various benzodiazepine (BZD) derivatives were used as first-line treatments, which were mostly used in line with the recommended guidelines. Levetiracetam was regularly used (n=42) and mostly in combination with BZDs, but no significant additional effect was observed for intravenous levetiracetam. However, it appeared that the administered doses tended to be low. CONCLUSIONS: Levetiracetam can be applied to adults with SE in prehospital settings with little effort. Nevertheless, the prehospital treatment regimen described here for the first time did not significantly improve the preclinical cessation rate of SE. Future therapy concepts should be based on this, and the effects of higher doses should in particular be reexamined.

Status epilepticus and benzodiazepine treatment: Use, underdosing and outcome - insights from a retrospective, multicentre registry.

OBJECTIVE: To explore the reasons for and outcomes of non- or undertreatment with benzodiazepines (BZDs) in status epilepticus (SE). METHODS: We retrospectively analysed all SE patients from the urban area of Cologne over two years. RESULTS: 328 SE patients were eligible, and only 72% were initially treated with BZDs. Of these, only 21.6% were treated sufficiently with BZDs according to current guidelines. SE patients not initially treated with BZDs were significantly older, had less often known epilepsy, had a prolonged arrival time to the emergency room, and presented more often with a non-generalised convulsive semiology. Regarding adequate dosages, patients with a generalised convulsive SE seemed to benefit from a sufficient BZD dosing with significantly shortened mean ventilation duration (37.1 to 208 h), decreased mean intensive care unit (1.7 to 5 days) and in-hospital stay (4.1 to 8.8 days). In contrary, aggressive BZD treatment in non-generalised convulsive SE resulted in a longer inpatient stay (9.2 to 5.8 days) and lower favourable outcome rates at discharge (16% to 63%). CONCLUSIONS: The current SE treatment guidelines for first-line BZD therapy in SE were violated in most patients. Sufficient BZD dosing was beneficial in generalised convulsive SE, but not in other forms of SE. SE semiology might be crucial for treatment decisions with BZDs. Further treatment evidence especially in non-generalised convulsive SE is urgently needed.

Prognosis and management of acute symptomatic seizures: a prospective, multicenter, observational study.

BACKGROUND: Acute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%. METHODS: Inclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey. RESULTS: Eleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%-16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8-69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0-9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate. CONCLUSIONS: Even in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment.

Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response.

BACKGROUND: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis. METHODS: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays. RESULTS: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome. CONCLUSIONS: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.

Super-refractory status epilepticus in adults.

INTRODUCTION: Super-refractory status epilepticus (SRSE) represents the culmination of refractory status epilepticus (RSE) and carries a significant risk of poor neurological outcome and high mortality. RSE is not defined primarily by seizure duration, but by failure to respond to appropriate antiseizure treatment. SRSE is present when a RSE persists or recurs after more than 24 h of treatment with anesthetics. No evidence-based treatment algorithms can be provided for SRSE. Therefore, we propose a pragmatic standard operating procedure (SOP) for the management of SRSE that addresses the existing uncertainties in the treatment of SRSE and provides options for resolution and decision-making. COMMENTS: First, we recommend the assessment of persistent seizure activity and the evaluation of differential diagnoses to confirm correct diagnosis. Relevant differential diagnoses include psychogenic non-epileptic seizures, hypoxic, metabolic, or toxic encephalopathies, and tetanus. During SE or in severe encephalopathies, a so-called electroclinical ictal-interictal continuum may occur, which denotes an intermediate stage that cannot be defined with certainty as ictal or interictal by EEG and should not lead to harmful overtreatment. Because both prognosis and specific treatment options depend crucially on the etiology of SRSE, the etiological evaluation should be performed rapidly. When SRSE is confirmed, various pharmacological and non-pharmacological treatment options are available. CONCLUSION: We provide a pragmatical SOP for adult people with SRSE.

Status epilepticus during the COVID-19 pandemic in Cologne, Germany: data from a retrospective, multicentre registry.

BACKGROUND: The "coronavirus disease 2019" (COVID-19) pandemic, caused by the "severe-acute-respiratory-syndrome-coronavirus 2" (SARS-CoV-2), challenges healthcare systems worldwide and impacts not only COVID-19 patients but also other emergencies. To date, data are scarce on the extent to which the COVID-19 pandemic impacted status epilepticus (SE) and its treatment. OBJECTIVE: To assess the influence of the COVID-19 pandemic on the incidence, management and outcome of SE patients. STUDY DESIGN: This is a retrospective, multicentre trial, approved by the University of Cologne (21-1443-retro). METHODS: All SE patients from the urban area of Cologne transmitted to all acute neurological departments in Cologne between 03/2019 and 02/2021 were retrospectively analysed and assessed for patient characteristics, SE characteristics, management, and outcome in the first pandemic year compared to the last pre-pandemic year. RESULTS: 157 pre-pandemic (03/2019-02/2020) and 171 pandemic (from 03/2020 to 02/2021) SE patients were included in the analyses. Acute SARS-CoV-2 infections were rarely detected. Patient characteristics, management, and outcome did not reveal significant groupwise differences. In contrast, regarding prehospital management, a prolonged patient transfer to the hospital and variations in SE aetiologies compared to the last pre-pandemic year were observed with less chronic vascular and more cryptogenic and anoxic SE cases. No infections with SARS-CoV-2 occurred during inpatient stays. CONCLUSIONS: SARS-CoV-2 infections did not directly affect SE patients, but the transfer of SE patients to emergency departments was delayed. Interestingly, SE aetiology rates shifted, which warrants further exploration. Fears of contracting an in-hospital SARS-CoV-2-infection were unfounded due to consequent containment measures.

IGNITE Status Epilepticus Survey: A Nationwide Interrogation about the Current Management of Status Epilepticus in Germany.

We aimed to evaluate the current management of status epilepticus (SE) in intensive care units (ICUs) in Germany, depending on the different hospital levels of care and the ICU specialty. We performed a nationwide web-based anonymized survey, including all German ICUs registered with the German Society for Neurointensive and Emergency Care (Deutsche Gesellschaft für Neurointensiv- und Notfallmedizin; DGNI). The response rate was 83/232 (36%). Continuous EEG monitoring (cEEG) was available in 86% of ICUs. Regular written cEEG reports were obtained in only 50%. Drug management was homogeneous with a general consensus regarding substance order: benzodiazepines-anticonvulsants-sedatives. Thereunder first choice substances were lorazepam (90%), levetiracetam (91%), and propofol (73%). Data suggest that network structures for super-refractory SE are not permeable, as 75% did not transfer SE patients. Our survey provides "real world data" concerning the current management of SE in Germany. Uniform standards in the implementation of cEEG could help further improve the overall quality. Initial therapy management is standardized. For super-refractory SE, a concentration of highly specialized centers establishing network structures analogous to neurovascular diseases seems desirable to apply rescue therapies with low evidence carefully, ideally collecting data on this rare condition in registries and clinical trials.

Seizure Semiology in Antibody-Associated Autoimmune Encephalitis.

BACKGROUND AND OBJECTIVES: To 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). METHODS: Multicenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis. RESULTS: Three 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 (23/26; 88%). An aura with déjà-vu phenomenon was nearly specific in GAD+ patients (16/20, 80%). Faciobrachial dystonic seizures (FBDS) were uniquely observed in LGI1+ patients (17/59, 29%). Status epilepticus was reported in one-third of NMDAR+ patients, but only rarely in the 2 other groups. The occurrence of seizures was associated with higher disease severity only in NMDAR+ patients. DISCUSSION: Seizures are a frequent and diagnostically relevant symptom of ab + AE. Whereas NMDAR+ patients had few localizing semiological features, semiology in LGI1+ and GAD+ patients pointed toward a predominant temporal seizure onset. FBDS are pathognomonic for LGI1 + AE. Status epilepticus seems to be more frequent in NMDAR + AE.