Neurological Research and Practice最新文献

Background: The ALS Functional Rating Scale in its revised version (ALSFRS-R) is a disease-specific severity score that reflects motor impairment and functional deterioration in people with amyotrophic lateral sclerosis (ALS). It has been widely applied in both clinical practice and ALS research. However, in Germany, several variants of the scale, each differing slightly from the others, have developed over time and are currently in circulation. This lack of uniformity potentially hampers data interpretation and may decrease item validity. Furthermore, shortcomings within the standard ALSFRS-R questions and answer options can limit the quality and conclusiveness of collected data.

Methods: In a multistage consensus-building process, 18 clinical ALS experts from the German ALS/MND network analyzed the ALSFRS-R in its current form and created an adapted, annotated, and revised scale that closely adheres to the well-established standardized English version.

Results: Ten German-language variants of the ALSFRS-R were collected, three of which contained instructions for self-assessment. All of these variants were compiled and a comprehensive linguistic revision was undertaken. A short introduction was added to the resulting scale, comprising general instructions for use and explanations for each of the five reply options per item. This adapted version of the scale, named ALSFRS-R-SE (with the "SE" referring to "self-explanatory"), was carefully reviewed for language and comprehensibility, in both German and English.

Conclusion: An adapted and annotated version of the ALSFRS-R scale was developed through a multistage consensus process. The decision to include brief explanations of specific scale items and reply options was intended to facilitate ALSFRS-R-SE assessments by both healthcare professionals and patients. Further studies are required to investigate the accuracy and utility of the ALSFRS-R-SE in controlled trials and clinical real-world settings.

Introduction: Post-stroke depression (PSD) is an important and frequent non-motor complication after a stroke. As valid prediction of PSD occurrence is still not possible, the unselective use of preventive therapy in stroke patients has risen a questionable risk-to-benefit consideration. Therefore, there is a need to increase the prediction probability of PSD to identify patients at very high risk of a depressive complication who might benefit from preventive therapy. In this context, a brainstem raphe hypoechogenicity (BRH) in transcranial sonography (TCS) has previously been associated with depressive symptoms in a broad spectrum of diseases. BRH might therefore represent a valid maker of vulnerability for depressive symptoms that could be of interest in the risk assessment of PSD occurrence.

Methods: In the prognostic markers of post-stroke depression (PROMoSD) study, a prospective, observational, single-center, investigator-initiated study, we aim to include 100 patients with acute ischemic stroke (AIS). Besides data on clinical characteristics and baseline psychiatric assessment, we conduct a TCS examination to identify patients with BRH. The primary outcome is the incidence of PSD three months after inclusion, determined by a blinded investigator according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria.

Perspective: The results of PROMoSD will answer the question of whether screening of BRH after AIS improves the prediction of PSD occurrence. A positive result of this study could have direct consequences on psychiatric support after AIS by streamlining diagnostic and therapeutic algorithms. Trial registration ClinicalTrials.gov identifier no. NCT05580198.

Background: Patients with a left (LHS) or right hemispheric stroke (RHS) differ in terms of clinical symptoms due to lateralization of specific cortical functions. Studies on functional outcome after stroke and endovascular thrombectomy (EVT) comparing both hemispheres showed conflicting results so far. The impact of stroke laterality on patient-reported health-related quality of life (HRQoL) after EVT has not yet been adequately addressed and still remains unclear.

Methods: Consecutive stroke thrombectomy patients, derived from a multi-center, prospective registry (German Stroke Registry) between June 2015 and December 2019, were included in this study. At 90 days, outcome after EVT was assessed by the modified Rankin scale (mRS) and HRQoL using the European QoL-five dimensions questionnaire utility-index (EQ-5D-I; higher values indicate better HRQoL) in patients with LHS and RHS. Adjusted regression analysis was applied to evaluate the influence of stroke laterality on outcome after EVT.

Results: In total, 5683 patients were analyzed. Of these, 2953 patients (52.8%) had LHS and 2637 (47.2%) RHS. LHS patients had a higher baseline NIHSS (16 vs. 13, p < 0.001) and a higher ASPECTS (9 vs. 8, p < 0.001) compared to RHS patients. Among survivors, patients with LHS less frequently had a self-reported affected mobility (p = 0.037), suffered less often from pain (p = 0.04) and anxiety/depression (p = 0.032) three months after EVT. After adjusting for confounders (age, sex, baseline NIHSS), LHS was associated with a better HRQoL (ß coefficient 0.04, CI 95% 0.017-0.063; p = 0.001), and better functional outcome assessed by lower values on the mRS (ß coefficient - 0.109, CI 95% - 0.217-0.000; p = 0.049).

Conclusions: Ninety days after EVT, LHS patients have a better functional outcome and HRQoL. Patients with RHS should be actively assessed and treated for pain, anxiety and depression to improve their HRQoL after EVT.

Background: Misdiagnosis of seizure-like events (SLE) in emergency situations is common. Here, we evaluate whether a single, video-based lesson highlighting distinguishing semiological features can improve the diagnostic accuracy of emergency physicians for epileptic seizures (ES), psychogenic non-epileptic seizures (PNES) and syncopes (SY).

Methods: 40 emergency physicians (24 anesthetists, nine surgeons and seven internal medicine specialists by primary specialty) participated in a prospective trial on the diagnostic accuracy of SLE. They assessed video-displayed SLE at two time points: before and after a lecture on distinguishing semiological features. In the lecture, semiological features were demonstrated using patient videos, some were acted by the instructor in addition. The increase in correct diagnoses and recognition of distinguishing semiological features were analyzed.

Results: Before the lesson, 45% of 200 SLE-ratings were correct: 15% of SY (n = 40), 30% of PNES (n = 40), 59% of ES (n = 120, focal to bilateral tonic-clonic seizures (FBTCS) 87.5% (n = 40), focal impaired aware seizures (FIAS) 45% (n = 80)). Semiology teaching increased both the rate of correct diagnoses of SLE to overall 79% (p < 0.001) (ES 91% (p < 0.001), FBCTS 98% (n.s.), FIAS 88% (p < 0.001), PNES 88% (p < 0.001), SY 35% (p < 0.001)), and the number of recognized distinguishing semiological features. We identified several semiological features with high entity specific positive predictive values (> 0.8).

Conclusions: A single 45-min video-based lesson highlighting distinguishing semiological features improves the diagnostic accuracy of ES, PNES and SY by emergency physicians. We expect that including this aspect into the curriculum of emergency physicians will lead to better individual patient treatment in pre-hospital medicine and more appropriate subsequent use of clinical resources.

The gut contains the largest reservoir of microorganisms of the human body, termed as the gut microbiota which emerges as a key pathophysiological factor in health and disease. The gut microbiota has been demonstrated to influence various brain functions along the "gut-brain axis". Stroke leads to intestinal dysmotility and leakiness of the intestinal barrier which are associated with change of the gut microbiota composition and its interaction with the human host. Growing evidence over the past decade has demonstrated an important role of these post-stroke changes along the gut-brain axis to contribute to stroke pathology and be potentially druggable targets for future therapies. The impact of the gut microbiota on brain health and repair after stroke might be attributed to the diverse functions of gut bacteria in producing neuroactive compounds, modulating the host's metabolism and immune status. Therefore, a better understanding on the gut-brain axis after stroke and its integration in a broader concept of stroke pathology could open up new avenues for stroke therapy. Here, we discuss current concepts from preclinical models and human studies on the bi-directional communication along the microbiota-gut-brain axis in stroke.

Background: Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing-remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape.

Methods: We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions.

Results: Under siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy.

Conclusion: Treatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.

Seizure Related 6 Homolog Like 2 (SEZ6L2) protein has been shown to have implications in neuronal and especially motor function development. In oncology, overexpression of SEZ6L2 serves as a negative prognostic marker in several tumor entities. Recently, few cases of anti-SEZ6L2 antibody mediated cerebellar syndromes were reported. In this article, we present a case of a 70-year-old woman with subacute onset of gait disturbance, dysarthria and limb ataxia. Serum anti-SEZ6L2 antibodies were markedly increased, and further diagnostic workup revealed left sided breast cancer. Neurological symptoms and SEZ6L2 titer significantly improved after curative tumor therapy. This is a very rare and educationally important report of anti-SEZ6L2 autoimmune cerebellar syndrome with a paraneoplastic etiology. Additionally, we performed a review of the current literature for SEZ6L2, focusing on comparing the published cases on autoimmune cerebellar syndrome.

Recent studies have indicated that long-term neurological sequelae after COVID-19 are not accompanied by an increase of canonical biomarkers of central nervous system injury in blood, but subgroup stratifications are lacking. This is a particular concern in chronic headache, which can be a leading symptom of Post-COVID diseases associated with neuronal damage such as vasculitis or autoimmune encephalitis. We here compared patients with mild Post-COVID-19 syndrome and persistent headache (persistent Post-COVID-19 headache) lasting longer than 12 weeks after the initial serological diagnosis, to patients with mild and severe COVID-19 and COVID-19-negative controls. Levels of neurofilament light chain and glial fibrillary astrocytic protein, i.e. markers of neuronal damage and reactive astrogliosis, were lower in blood from patients with persistent Post-COVID-19 headache compared to patients with severe COVID-19. Hence, our pilot serological study indicates that long-term Post-COVID-19 headache may not be a sign of underlying neuronal damage or neuroinflammation.

Background: In the treatment of status epilepticus less is known about the influence of comorbidities on the safety profile of anticonvulsive drugs. Especially patients with diabetes mellitus may be predisposed to certain adverse events that have been related to therapy with valproic acid. In this single-center retrospective cohort study we examined if the complications of the intravenous treatment with valproic acid is different in patients with or without diabetes.

Methods: Patients who were treated for status epilepticus with intravenous valproic acid between 2008 and 2020 were identified. Primary endpoint was the discontinuation of therapy with valproic acid due to adverse events. Relevant secondary endpoints were the functional status at the time of discharge from hospital in comparison to the premorbid state and the in-hospital mortality. Both groups (patients with or without diabetes) were compared by Mann-Whitney U-Test or Pearson´s Chi² test. To identify therapy with valproic acid as a risk factor of in-hospital mortality, a binary regression model was used.

Results: During the study period 408 patients and 482 episodes of status epilepticus were treated with intravenous valproic acid. Group comparisons did not reveal a significant difference in the rates of discontinuation of therapy. A difference was found in the rate of thrombocytopenia (p = 0.015), which occurred more often in patients with diabetes. In total, 36 hypoglycemic episodes could be identified, two occurred spontaneously under intravenous valproic acid. After correction for potential confounders, continuous therapy with valproic acid could not be confirmed as an independent risk factor for in-hospital mortality (p = 0.079). In patients with diabetes, the proportion of patients with a good functional state, indicated by the modified Rankin Scale, was significantly lower in both times (premorbid: 55% vs. 69%, p = 0.008; at discharge: 22% vs. 36%, p = 0.004).

Conclusions: Tolerability of the treatment with valproic acid was similar in patients with or without diabetes. Diabetes as a relevant comorbidity can signal a potentially increased risk of a poor outcome after status epilepticus.

Trial registration: The study was registered at the German Clinical Trials Register on 8 April 2022 (DRKS 00,027,836).

Background: Although there are well known sex differences in older patients with ischemic stroke receiving acute reperfusion treatments, there is paucity of data in younger patients.

Methods: We investigated sex-related differences in clinical presentation, stroke etiology and short-term outcomes in consecutive young patients with acute ischemic stroke (AIS) below the age of 50 years receiving mechanical thrombectomy (MT) between January 2011 and May 2021 in a tertiary stroke center.

Results: We identified a total of 202 young ischemic stroke patients with MT, with 51% being female. Young female AIS patients were significantly younger (39 ± 8 vs. 43 ± 7 years, p < 0.001), and presented with a trend for more severe stroke on admission (median NIHSS 12 vs. 9, p = 0.065), compared to males, respectively. Young female AIS patients had higher rates of embolic strokes of determined or undetermined sources in the anterior circulation, while young male AIS patients suffered more often strokes of arterio-arterial embolism. Complete reperfusion (TICI score 3) was achieved significantly less often in young female AIS patients (69% vs. 83%, p = 0.006), and in-hospital mortality was 2-times higher (5% vs. 2%, p = 0.271) compared to males.

Conclusions: Young female AIS patients receiving MT have higher rates of severe embolic strokes and less often complete reperfusion due to different occlusion sites and stroke etiology compared to males.