[Acute Aortic Dissection: A Life-Threatening Disease Also in Neurological Emergency Medicine]. / Akute Aortendissektion: Ein lebensbedrohlicher Notfall auch in der neurologischen Notfallmedizin.

Acute aortic dissection is rare but life-threatening. The symptoms depend on the localization and reduced perfusion of the downstream organs or limbs and are therefore variable. Neurological symptoms may occur that do not immediately lead to a diagnosis and thus delay the necessary therapy. Knowing the early symptoms and warning signs of aortic dissection is therefore also crucial in neurological emergency care for quickly identifying the affected patients and for providing acute therapy. A misdiagnosis with delayed initiation of therapy can significantly worsen the patient's outcome. This study aims to establish a standardized diagnostic and therapeutic algorithm for suspected acute aortic dissection in neurological emergency care. Close interdisciplinary cooperation is mandatory.

[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.

[Ciguatera or why you should enquire about fish consumption in cases of cold allodynia]. / Ciguatera oder wieso bei der Kälteallodynie nach dem Fischverzehr gefragt werden sollte.

Ciguatoxine sind potente, von Mikroalgen produzierte, marine Biotoxine, die sich in tropischen Raubfischen, lokal und saisonal unterschiedlich stark, anreichern können. Kurze Zeit nach dem Fischverzehr treten gastrointestinale, neurologische und/oder kardiovaskuläre Vergiftungssymptome auf. Durch die hohe Affinität der Toxine zu neuronalen Natriumkanälen sind neurologische Symptome für Ciguatera-Vergiftungen charakteristisch. Nahezu pathognomonisch ist dabei die Kälteallodynie, bei der kalte Oberflächen als heiß, schmerzhaft oder extrem unangenehm empfunden werden. Durch Importe von Tropenfisch tritt Ciguatera zunehmend auch in gemäßigten Klimazonen auf. Wir erläutern anhand zweier Fälle die Besonderheiten dieser Fischvergiftung.

[Early Diagnosis of Chorea-Acanthocytosis: Orofacial Dyskinesia, Epileptic Seizures, and HyperCKemia]. / Frühdiagnose der Chorea-Akanthozytose: orofaziale Dyskinesien, epileptische Anfälle und HyperCKämie.

Chorea-acanthocytosis is an uncommon neurodegenerative disorder. Early diagnosis is often challenging. The triad of orofacial dyskinesia, epileptic seizures, and hyperCKemia should alert neurologists of a neuroacanthocytosis syndrome. The diagnosis can be confirmed by detection of chorein deficiency or through molecular genetics (VPS13A mutation).

Time reproduction deficits in essential tremor patients.

BACKGROUND: Although motor symptoms predominate in essential tremor, increasing evidence indicates additional cognitive deficits. According to the pivotal role of cognitive functioning for temporal information processing and acknowledging the relevance of temporal information processing for movement coordination, we investigated whether essential tremor patients exhibit time reproduction deficits. METHODS: A total of 24 essential tremor patients and 24 healthy controls performed sub- and suprasecond visual duration reproduction tasks of 500 to 900 milliseconds and 1.6 to 2.4 seconds, respectively. To differentiate deficient time processing from motor or other cognitive dysfunctions, the average temporal reproduction errors were correlated with tremor severity, immediate and delayed word-list recall performance, and verbal fluency. RESULTS: Essential tremor patients significantly underreproduced sub- and suprasecond time intervals longer than 800 milliseconds. Moreover, time compression correlated significantly with semantic verbal fluency and word-list retrieval performance, but not with tremor severity. CONCLUSION: Data suggest impaired temporal processing in essential tremor, corroborating evidence for specific cognitive deficits. © 2016 International Parkinson and Movement Disorder Society.

Posterior reversible encephalopathy syndrome and stroke after intravenous immunoglobulin treatment in Miller-Fisher syndrome/Bickerstaff brain stem encephalitis overlap syndrome.

The association of a posterior reversible encephalopathy syndrome (PRES) without arterial hypertension with autoimmune-mediated inflammatory neuropathies such as Guillain-Barré syndrome (GBS) is a rare and poorly understood phenomenon. To date, PRES has been described as initial manifestation, coincidental finding, or adverse event subsequent to immunomodulatory treatment with intravenous immunoglobulin (IVIG) in cases of axonal and demyelinating GBS as well as in Miller-Fisher syndrome (MFS). We here report a case of MFS/Bickerstaff brain stem encephalitis (BBE)-overlap syndrome and nonhypertensive PRES that occurred in close temporal association with IVIG treatment and caused stroke. Immunoadsorption ameliorated the disease course. Our case supports the notion that in severe cases, immunoadsorption should be considered as first-line therapy instead of IVIG for rapid removal of IgG and thus to hasten recovery and improve functional outcome.

Prognostic value of electroencephalography and evoked potentials in the early course of malignant middle cerebral artery infarction.

Space-occupying brain edema may lead to a malignant course in patients with large middle cerebral artery infarction. Decompressive hemicraniectomy has to be initiated early to prevent further tissue damage. In this retrospective study, we analyzed electroencephalography (EEG) and evoked potentials (EPs), obtained within 24 h after onset of stroke, in 22 patients suffering from a large middle cerebral artery infarction. Our findings indicate a prognostic value of EEG and brainstem auditory EP (BAEP): the absence of delta activity and the presence of theta and fast beta frequencies within EEG-focus predicted a non-malignant course. In contrast, diffuse generalized slowing and slow delta activity in the ischemic hemisphere pointed to a malignant course. Likewise, pathological BAEP were correlated with a malignant course. The coexistence of background slowing and pathological BAEP showed the highest level of significance. In conclusion, our findings implicate an additional early application of electrophysiological methods in stroke patients. EEG and EP deliver useful information to select those patients who develop malignant edema.

Sex differences in polysomnographic findings in patients with obstructive sleep apnea.

BACKGROUND AND PURPOSE: Sex differences in the clinical findings and the polysomnographic presentation of patients with obstructive sleep apnea (OSA) are compelling current research issues. For example, patients suffering from obstructive sleep apnea are predominantly male. While women are older than men and tend to have a higher body mass index, men typically present with a more severe form of obstructive sleep apnea. Using polysomnography, we investigated a German cohort, subdivided per severity levels of obstructive sleep apnea (apnea-hypopnea index: ≥5 to < 15/h (mild), ≥15 to < 30/h (moderate), and ≥30/h (severe)) to provide a detailed analysis of breathing and sleep parameters, accounting for body position effects and severity of illness. A deeper understanding of sex differences may allow targeted diagnosis and treatment adjustment. PATIENTS AND METHODS: This retrospective study included a cohort of 1242 German patients (940 male, 302 female) who underwent overnight polysomnography at the private sleep laboratory "Intersom Köln", Center for Sleep Medicine and Sleep Research. In 1125 subjects (878 male, 247 female), obstructive sleep apnea was diagnosed. All patients were examined between January 01, 2018 and December 31, 2020, comparing anthropometric, sleep morphological, and respiratory polysomnographic findings. RESULTS: Female patients with obstructive sleep apnea were significantly older than male patients (60.9 ± 12.3 vs. 56.9 ± 12.5 years, P < .001), also among OSA subgroups per OSA severity. The body mass index was similar in male and female patients (29.6 ± 5.1 vs. 29.2 ± 7.3 kg/m2, P > .05), including the three subgroups. Men were more likely to have severe obstructive sleep apnea (46.9%) than women (35.2%). Women exhibited a higher proportion of slow-wave sleep than men (129.4 ± 52.8 vs. 104.2 ± 53.2 min; P < .001). The apnea-hypopnea index of total sleep time was significantly greater in male than female patients (32.9 ± 21.2 vs. 27.2 ± 20.2 per hour; P < .001). Female patients had a higher apnea-hypopnea index during rapid-eye-movement (REM) sleep (34.0 ± 23.8 vs. 31.8 ± 22.3 per hour; P = .171). A statistically significant difference in the apnea-hypopnea index during REM sleep between sexes was found when the obstructive sleep apnea severity was considered. Women had a lower apnea-hypopnea index in non-rapid eye-movement (NREM) sleep than men (25.7 ± 21.1 vs. 32.7 ± 22.3 per hour; P < .001). The oxygen desaturation index (29.9 ± 20.3 vs. 22.4 ± 19.4%; P < .001) and an oxygen desaturation below 90% (9.4 ± 14.0 vs. 6.8 ± 11.7%; P = .003) was greater in men than in women. In severe obstructive sleep apnea, the oxygen desaturation index was similar between the sexes (45.0 ± 17.8 vs. 41.1 ± 20.9%; P = .077). Male patients showed a higher supine apnea-hypopnea-index than female patients. (45.7 ± 26.7 vs 36.1 ± 22.7 per hour; P < .001). CONCLUSION: The present noninvasive, retrospective registry study is the first to examine sex differences in OSA in such a large German population in terms of respiratory and sleep parameters, taking into account the effects of body position and severity of the disease. We could confirm and extend observations from previous studies. Female patients were significantly older than the male patients. The apnea-hypopnea index was higher in male than in female patients. Women showed a higher apnea-hypopnea index in REM sleep and a lower one in NREM sleep. Men were desaturated more often and were more affected by supine-dependent obstructive sleep apnea than women. Contrary to the literature, there were no significant differences in body mass index (BMI) between the sexes. With increasing age and BMI, the gender differences become less significant.

Solriamfetol real world experience study (SURWEY): Initiation, titration, safety, effectiveness, and experience during follow-up for patients with narcolepsy from Germany.

BACKGROUND: Excessive daytime sleepiness (EDS) is a core narcolepsy symptom, for which solriamfetol (Sunosi®) was recently approved in the European Union. SURWEY characterises real-world strategies used by physicians when initiating solriamfetol, and patient outcomes after follow-up. METHODS: SURWEY is an ongoing retrospective chart review conducted by physicians in Germany/France/Italy. Here, data are reported from 70 German patients with EDS and narcolepsy. Eligibility included age ≥18 years, reached a stable solriamfetol dose, and completed ≥6 weeks of treatment. Patients were classified (based on existing EDS treatment) into changeover, add-on, or new-to-therapy subgroups. RESULTS: Patients' mean ± SD age was 36.9 ± 13.9 years. Changeover from prior EDS medication was the most common initiation strategy. Initial solriamfetol dose was typically 75 mg/day (69%). In 30 patients (43%), solriamfetol was titrated; 27/30 (90%) completed titration as prescribed, most within 7 days. Mean ± SD Epworth Sleepiness Scale (ESS) score was 17.6 ± 3.1 at initiation (n = 61) and 13.6 ± 3.8 at follow-up (n = 51). Slight/strong improvements in EDS were perceived for >90% of patients (patient and physician report). Sixty-two percent reported an effect duration of 6 to <10 h; 72% reported no change in perceived nighttime sleep quality. Common adverse events included headache (9%), decreased appetite (6%), and insomnia (6%); no cardiovascular events were reported. CONCLUSIONS: Most patients in this study were switched from a prior EDS medication to solriamfetol. Solriamfetol was typically initiated at 75 mg/day; titration was common. ESS scores improved after initiation, and most patients perceived improvement in EDS. Common adverse events were consistent with those reported in clinical trials. GOV REGISTRATION: N/A.

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.

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.

Communication, Coordination, and Security for People with Multiple Sclerosis (COCOS-MS): a randomised phase II clinical trial protocol.

INTRODUCTION: Patients with multiple sclerosis (MS) have complex needs that range from organising one's everyday life to measures of disease-specific therapy monitoring to palliative care. Patients with MS are likely to depend on multiple healthcare providers and various authorities, which are often difficult to coordinate. Thus, they will probably benefit from comprehensive cross-sectoral coordination of services provided by care and case management (CCM). Though studies have shown that case management improves quality of life (QoL), functional status and reduces service use, such benefits have not yet been investigated in severely affected patients with MS. In this explorative phase ll clinical trial, we evaluated a CCM with long-term, cross-sectoral and outreaching services and, in addition, considered the unit of care (patients and caregivers). METHODS AND ANALYSIS: Eighty patients with MS and their caregivers will be randomly assigned to either the control (standard care) or the intervention group (standard care plus CCM (for 12 months)). Regular data assessments will be done at baseline and then at 3-month intervals. As primary outcome, we will evaluate patients' QoL. Secondary outcomes are patients' treatment-related risk perception, palliative care needs, anxiety/depression, use of healthcare services, caregivers' burden and QoL, meeting patients' and caregivers' needs, and evaluating the CCM intervention. We will also evaluate CCM through individual interviews and focus groups. The sample size calculation is based on a standardised effect of 0.5, and one baseline and four follow-up assessments (with correlation 0.5). Linear mixed models for repeated measures will be applied to analyse changes in quantitative outcomes over time. Multiple imputation approaches are taken to assess the robustness of the results. The explorative approach (phase ll clinical trial) with embedded qualitative research will allow for the development of a final design for a confirmative phase lll trial. ETHICS AND DISSEMINATION: The trial will be conducted under the Declaration of Helsinki and has been approved by the Ethics Commission of Cologne University's Faculty of Medicine. Trial results will be published in an open-access scientific journal and presented at conferences. TRIAL REGISTRATION NUMBER: German Register for Clinical Studies (DRKS) (DRKS00022771).

Immunoadsorption in patients with chronic inflammatory demyelinating polyradiculoneuropathy with unsatisfactory response to first-line treatment.

BACKGROUND/AIMS: First-line treatment options for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are corticosteroids, intravenous immunoglobulin, and plasma exchange. In a significant number of patients, first-line therapy fails, and long-term maintenance treatment still remains a therapeutic challenge. Immunoadsorption (IA) may be an alternative to classical plasma exchange in the therapy of immune-mediated neurologic diseases. The aim of this investigation was to evaluate efficacy and safety of IA in patients with CIDP with unsatisfactory response to first-line treatment options. METHODS: CIDP patients received adjunct IA treatment using tryptophan-immune adsorbers. The inflammatory neuropathy cause and treatment disability (INCAT) score was used to grade disability and monitor treatment effects. RESULTS: In total, 14 CIDP patients were analyzed. Ten patients were treated in hospital. After one IA treatment series, the INCAT score decreased significantly in all 10 patients. Four of these 14 patients were treated in outpatient clinics using long-term maintenance IA with 1-2 treatments per week. In these 4 patients, effects of long-term maintenance IA resulted in an improvement of overall disability. In all patients, IA was safe, well tolerated, and no severe adverse effects occurred. CONCLUSION: IA could be an effective and safe option for CIDP patients with unsatisfactory response to first-line treatment options and for long-term maintenance treatment.

Patient-tailored, imaging-guided, long-term temozolomide chemotherapy in patients with glioblastoma.

We present two patients with glioblastoma with an unusually stable clinical course and long-term survival who were treated after surgery and radiotherapy with adjuvant temozolomide (TMZ) chemotherapy for 17 and 20 cycles, respectively. Afterward, adjuvant TMZ chemotherapy was discontinued in one patient and the dosage of TMZ was reduced in the other. In addition to clinical status and magnetic resonance imaging, the biologic activity of the tumors was monitored by repeated methyl-11C-l-methionine (MET) and 3'-deoxy-3'-18F-fluorothymidine (FLT) positron emission tomography (PET) studies in these patients. In these patients, repeated MET- and FLT-PET imaging documented complete response to the initial treatment regimen, including resection, radiation, and TMZ, and during the course of the disease, recurrent, uncontrollable tumor activity. Continuation or dose escalation of TMZ in both patients was shown to be ineffective to overcome the metabolic activity of the tumor. Our data suggest that repeated MET- and FLT-PET imaging provide information on the biologic activity of a tumor that is highly useful to monitor and detect changes in activity.

Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany-Updated series of 120 cases.

BACKGROUND: Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth. AIMS: To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage. METHODS: Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used. RESULTS: One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0-3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay. CONCLUSION: Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

Ten Hertz thalamus stimulation increases tremor activity in the subthalamic nucleus in a patient with Parkinson's disease.

OBJECTIVE: In patients with Parkinson's disease (PD) the effect of thalamic stimulation on tremor pathophysiology remains largely unclear. By recording local field potentials (LFPs) in the subthalamic nucleus (STN) while stimulating the nucleus ventralis intermedius thalami (VIM), information of the stimulation effects should be gained. METHODS: We had the unique opportunity to intraoperatively record LFPs of the STN in a patient with PD while stimulating the VIM. VIM electrodes had been implanted 9 years previously because of tremor. Due to worsening of clinical symptoms an implantation of STN electrodes had become necessary. RESULTS: High frequency stimulation in the VIM lowered the power of the tremor frequency band (4-7Hz) in the STN. In contrast, 10Hz VIM stimulation elevated the power of the tremor frequency band as well as STN-EMG coupling. CONCLUSIONS: The effect of high frequency stimulation may explain the improvement of tremor in patients who are treated with VIM deep brain stimulation. The power elevation during 10Hz stimulation suggests that the pathological cerebral and cerebral-muscular communication in PD is mainly driven at 10Hz. SIGNIFICANCE: The direct cerebral recordings support the view that a 10Hz network is a pathophysiological key mechanism in the generation of motor deficits in PD.

FET PET in Primary Central Nervous System Vasculitis.

Primary central nervous system vasculitis is confined to the brain and spinal cord. While serological markers of inflammation are usually normal, conventional angiography may confirm the diagnosis. The diagnostic method of choice is central nervous system biopsy. A 57-year-old man suffered from a first generalized epileptic seizure. MRI revealed a contrast-enhancing lesion, and O-(2-[F]fluoroethyl)-L-tyrosine amino acid PET displayed increased metabolic activity, both findings highly suggestive of a malignant glioma. Surprisingly, histology obtained following stereotactic biopsy revealed small-vessel vasculitis.