Search

ZusammenfassungMehr als 20% der Patienten mit idiopathischem Parkinson-Syndrom (IPS) entwickeln Psychosen. Am häufigsten sind visuelle Halluzinationen. Bei der Entwicklung der Psychosen scheinen die Pathogenese der Parkinson-Erkrankung sowie ihre Dauer ebenso eine Rolle zu spielen wie modulierende Effekte der dopaminergen Therapie. Beim Therapiemanagement steht neben allgemeinen Maßnahmen zunächst die Anpassung der dopaminergen Therapie im Vordergrund. Dies kann zu einer Gratwanderung werden zwischen Besserung der Halluzinationen und Verschlechterung der Motorik. Bei unzureichendem Erfolg kann eine antipsychotische Therapie notwendig werden – dabei ist die Auswahl auf sehr wenige Antipsychotika beschränkt, um nicht ernsthafte motorische Verschlechterungen zu riskieren. In der vorliegenden Arbeit wurden basierend auf dem aktuellen Stand der Literatur sowie empirischen Experten-basierten Erfahrungen aus dem klinischen Alltag relevante Aspekte zu Halluzinationen bei IPS-Patienten in der Praxis zusammengefasst und Empfehlungen zum Therapiemanagement erarbeitet.

We sought to determine the diagnostic agreement between the revised ultrasonography approach by the German Society of Ultrasound in Medicine (DEGUM) and the established Society of Radiologists in Ultrasound (SRU) consensus criteria for the grading of carotid artery disease. Post-hoc analysis of a prospective multicenter study, in which patients underwent ultrasonography and digital subtraction angiography (DSA) of carotid arteries for validation of the DEGUM approach. According to DEGUM and SRU ultrasonography criteria, carotid arteries were independently categorized into clinically relevant NASCET strata (normal, mild [1-49 %], moderate [50-69 %], severe [70-99 %], occlusion). On DSA, carotid artery findings according to NASCET were considered the reference standard. We analyzed 158 ultrasonography and DSA carotid artery pairs. There was substantial agreement between both ultrasonography approaches for severe (κw 0.76, CI95 %: 0.66-0.86), but only fair agreement for moderate (κw 0.38, CI95 %: 0.19-0.58) disease categories. Compared with DSA, both ultrasonography approaches were of equal sensitivity (79.7 % versus 79.7 %; p = 1.0) regarding the identification of severe stenosis, yet the DEGUM approach was more specific than the SRU approach (70.2 % versus 56.4 %, p = 0.0002). There was equality of accuracy parameters (p 0.05) among both ultrasonography approaches for the other ranges of carotid artery disease. While the sensitivity was equivalent, false-positive identification of severe carotid artery stenosis appears to be more frequent when using the SRU ultrasonography approach than the revised multiparametric DEGUM approach.ZIEL: Bestimmung der diagnostischen Übereinstimmung zwischen den multiparametrischen Ultraschallkriterien der Deutschen Gesellschaft für Ultraschall in der Medizin (DEGUM) und den Konsenskriterien der Society of Radiologists in Ultrasound (SRU) hinsichtlich der Graduierung von Karotisstenosen. Post-hoc-Analyse einer prospektiven multizentrischen Studie, welche die multiparametrischen DEGUM-Ultraschallkriterien mit der digitalen Subtraktionsangiografie validierte. Die Graduierung von Karotisstenosen in klinisch relevante NASCET-Kategorien (normal, leichtgradig (1–49 %), mittelgradig (50–69 %), hochgradig (70–99 %), Verschluss) erfolgte verblindet gemäß der DEGUM- und SRU-Ultraschallkriterien. Als Referenz wurde der nach NASCET bestimmte angiografische Stenosegrad verwendet. Wir analysierten 158 konsekutive Untersuchungen aus Ultraschall und Angiografie. Zwischen beiden sonografischen Graduierungsansätzen fand sich eine gute Übereinstimmung für hochgradige (κw 0,76; 95 %-KI 0,66–0,86) und eine mäßige Übereinstimmung für mittelgradige Stenosen (κw 0,38; 95 %-KI 0,19–0,58). Verglichen mit der Referenzangiografie fand sich kein Unterschied hinsichtlich Sensitivität für hochgradige Stenosen (79,7 % versus 79,7 %; p = 1,0), jedoch eine höhere Spezifität der DEGUM-Kriterien (70,2 % versus 56,4 %; p = 0,0002). In den sonstigen Stenosekategorien bestanden keine Unterschiede der Güteparameter (p 0,05). Verglichen mit den SRU-Kriterien weist die Graduierung nach DEGUM eine höhere Spezifität bei der Detektion hochgradiger Stenosen auf. Die Integration von mehr hämodynamischen Parametern scheint somit die Anzahl falsch positiver Diagnosen zu verringern.

Motor and non-motor symptoms (NMS) have a substantial effect on the health-related quality of life (QoL) of patients with Parkinson's disease (PD). Transdermal therapy has emerged as a time-tested practical treatment option, and the rotigotine patch has been used worldwide as an alternative to conventional oral treatment for PD. The efficacy of rotigotine on motor aspects of PD, as well as its safety and tolerability profile, are well-established, whereas its effects on a wide range of NMS have been described and studied but are not widely appreciated. In this review, we present our overall experience with rotigotine and its tolerability and make recommendations for its use in PD and restless legs syndrome, with a specific focus on NMS, underpinned by level 1–4 evidence. We believe that the effective use of the rotigotine transdermal patch can address motor symptoms and a wide range of NMS, improving health-related QoL for patients with PD. More specifically, the positive effects of rotigotine on non-motor fluctuations are also relevant. We also discuss the additional advantages of the transdermal application of rotigotine when oral therapy cannot be used, for instance in acute medical emergencies or nil-by-mouth or pre/post-surgical scenarios. We highlight evidence to support the use of rotigotine in selected cases (in addition to general use for motor benefit) in the context of personalised medicine.

Non-motor symptoms (NMS) occur in patients with cervical dystonia (CD) but with variable frequencies and impact on health-related quality of life (HRQoL). To define non-motor and motor profiles and their respective impact on HRQoL in CD patients using the newly validated Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest). In an observational prospective multicentre case–control study, we enrolled 61 patients with CD and 61 age- and sex-matched healthy controls (HC) comparing demographic data, motor and non-motor symptoms and HRQoL measurements. 95% CD patients reported at least one NMS. Mean total NMS score was significantly higher in CD patients (5.62 ± 3.33) than in HC (1.74 ± 1.52; p r = 0.72, EQ-5D: r = − 0.59; p

ObjectiveTo determine whether a fraction of patients with primary CNS lymphoma (PCNSL) had been cured by systemic and intraventricular methotrexate- and cytarabine-based chemotherapy (Bonn protocol) after a very long-term follow-up of nearly 20 years.MethodsSixty-five patients (median age 62 years, range 27–75; median Karnofsky performance score 70, range 20–90) had been treated with systemic and intraventricular polychemotherapy without whole brain radiotherapy from September 1995 until December 2001. All patients still alive in 2019 were contacted and interviewed on their current life situation.ResultsMedian follow-up for surviving patients was 19.6 years (17.5–23.3 years). Out of 65 patients, 11 (17%) were still alive. Six of those never experienced any relapse. For the whole study population, median overall survival (OS) was 4.4 years (95% confidence interval [CI] 2.9–5.9); for patients ≤60 years, 11.0 years (95% CI 4.8–17.0). The 10-year OS rate for the entire cohort was 29% and the estimated 20-year OS rate was 19%. Four late relapses were observed after 9.8, 10.3, 13.3, and 21.0 years.ConclusionAt a median follow-up of 19.6 years, 17% of patients were alive and free of tumor; however, even after response for decades, an inherent risk of relapse, either systemic or cerebral, characterizes the biology of PCNSL.Classification of evidenceThis work provides Class III evidence that PCNSL treatment with methotrexate-based polychemotherapy including intraventricular therapy is associated with long-term disease control in some patients.

Objective To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19). Methods In a retrospective multicenter study, we retrieved individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis. Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity. Results Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without [RR 2.07, 95% confidence interval (CI) 1.52–2.81; p p p p Conclusion A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19 suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.

ZusammenfassungIn einer Pilotstudie an 60 neurologischen Langzeitpatienten (degenerative zerebrale Mikroangiopathie mit reduzierter sensomotorischer Stabilität) erfolgt eine erste Überprüfung der Praxistauglichkeit eines eigens entwickelten Konzeptes, das in dem Kommunikationsaspekt einen Schwerpunkt der medizinischen Langzeitbehandlung sieht. Zunächst werden die Präferenzen des Patienten und weitere seine Adhärenz bestimmenden Faktoren analysiert. Neben Verständigung und sachlich-argumentativem Austausch bedarf es dabei einer affektiv-emotionalen vielschichtigen Botschaftsübermittlung, die sich auf den Rezipienten umfassend und in Echtzeit einstellt. Persuasion ist das gezielte Ansprechen von Verhaltensmustern. Gamification überführt spielerische Elemente in einen spielfremden Kontext. Dabei bieten technologiebasierte Ansätze eine Möglichkeit, Aspekte von Gesundheit, Lebensqualität und positiver Krankheitsbewältigung, z. B. durch den Einsatz von internet- und mobile-basierten Interventionen (IMI), zu optimieren. Auf diesem informationstheoretischen und gesundheitskommunikativen Hintergrund wurde eine Pilotstudie mit 60 neurologischen Langzeitpatienten mit symptomatischer zerebraler Mikroangiopathie durchgeführt, die wegen einer bestehenden sensomotorischen Inkompetenz stationär aufgenommen worden waren. Noch während des einwöchigen stationären Aufenthaltes bekamen die Patienten eine Einführung in eine standardisierte sensomotorische Trainingstherapie, die sie dann nach Entlassung aus dem stationären Setting über sechs Wochen hinweg als vierarmige Interventionsstudie ambulant am Klinikcampus oder häuslich, jeweils ohne und mit Gamification, weiterführten. Die Patienten wurden am Anfang und am Ende der Trainingsphase mit motorisch-funktionellen Verfahren und testpsychologisch untersucht. Anschließend wurden sie einem standardisierten Leitfadeninterview unterzogen. Als wichtigste Ergebnisse fanden sich:– Die computergestützte Trainingstherapie war wirksam und wurde von den Patienten angenommen. Ihnen war besonders wichtig: hohe Anwenderfreundlichkeit, hohe Präzision in der Widerspiegelung des Beherrschungsgrades auch subtiler Trainingselemente durch den Patienten und eine persönliche Fortschrittsbewertung in Echtzeit.– Die häuslichen Trainingsergebnisse waren besser als die in der Campusambulanz.– Training mit und ohne Gamification ist vergleichbar, es werden über sechs Wochen hinweg ähnliche Therapieeffekte erzielt, allerdings verbessert sich die subjektive Lebensqualität unter Gamification signifikant.

Zusammenfassung Hintergrund Nichtmotorische Symptome (NMS) bei Patienten mit Dystonie haben einen relevanten Einfluss auf die Lebensqualität. Ein rein auf NMS bei Dystonie bezogenes Messinstrument existiert nicht. Ziel Die validierte deutsche Version des Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest) zur Erhebung von NMS bei kraniozervikaler Dystonie wird hier vorgestellt. Methoden Der DNMSQuest in deutscher Sprache wurde nach international anerkannten Standards zum Vorgehen der interkulturellen Adaptation selbst auszufüllender Patientenfragebögen erstellt. So erfolgte die Übersetzung des englischen Originalfragebogens ins Deutsche sowie die Rückübersetzung unabhängig voneinander durch insgesamt vier bilinguale Neurologen mit Schwerpunkt Bewegungsstörungen. Von einem weiteren Neurologen wurde jeweils eine von den Übersetzern akzeptierte Konsensusfassung erstellt. Der englische Originalfragebogen wurde mit der rückübersetzten englischen Version von einem Neurologen mit maßgeblicher Beteiligung an der Entwicklung des Originalfragebogens auf sprachliche und inhaltliche Abweichungen kontrolliert. Die finale deutsche Version wurde bei 130 Patienten mit zervikaler Dystonie sowie 48 gesunden Kontrollen bei der internationalen, multizentrischen Validierungsstudie angewendet. Ergebnisse Es entstand eine interkulturell adaptierte, in deutscher und englischer Sprache validierte Fassung des DNMSQuest. Diskussion Der DNMSQuest kann die aktuell bestehende Lücke eines validierten, krankheitsspezifischen, durch die Patienten selbst auszufüllenden, kurzen, umfassenden Fragebogen zur Erhebung von NMS bei zervikaler Dystonie schließen. Er kann einfach in den klinischen Alltag integriert werden und empfiehlt sich für die klinische Praxis sowie zur Anwendung in klinischen Studien.

Periodic limb movements in sleep (PLMS) are repetitive movements usually of the legs strongly associated with Restless-legs syndrome (RLS), which appear more frequently in males, older age and other sleep disturbances, such as sleep-disordered breathing (SDB). Patients with Parkinson's disease (PD) suffer from various sleep disturbances including REM sleep behavior disorder, RLS and PLMS. Although a dopaminergic pathophysiology of PLMS is discussed, no systematic data on PLMS side-to-side distribution in PD and its correlation with asymmetry of motor symptoms are available.This study aimed at elucidating PLMS asymmetry in correlation to that of motor symptoms in PD compared to SDB and RLS.Cross-sectional, retrospective analysis of two polysomnography (PSG) recordings per patient scoring PLMS separately for both legs.Of 105 patients (44 PD, 44 age- and sex-matched SDB and 17 RLS patients) PLMS measures (number of PLM, PLM-Index, PLM-arousal index) showed significant side-to-side differences in all disease entities in both PSGs (P 5/h between both sides) was observed less frequently in PD (34% of patients) compared to RLS (77% , P

Background: Deep brain stimulation (DBS) is an established method of treatment for Parkinson’s disease (PD). A stimulation sweet spot at the interface between the motor and associative clusters of the subthalamic nucleus (STN) has recently been postulated. The aim of this study was to analyze the available clustering methods for the STN and their correlation to outcome. Methods: This is a retrospective analysis of a group of 20 patients implanted with a DBS device for PD. Atlas-based and diffusion tractography-based parcellation of the STN was performed. The distances of the electrode to the obtained clusters were compared to each other and to outcome parameters, which included levodopa equivalent dose (LED) reduction, Unified Parkinson’s Disease Rating Scale (UPDRS)-III scores, and reduction in scores for items 32 and 36 of the UPDRS-IV. Results: The implanted electrodes were located nearest to the motor clusters of the STN. The following significant associations with postoperative LED reduction were found: (1) distance of the electrode to the motor cluster in the Accolla and DISTAL atlases (p < 0.01) and (2) distance of the electrode to the supplementary motor area cluster (p = 0.02). There was no association with either the UPDRS-III or the UPDRS-IV score. Conclusions: The results of this study suggest the possibility that atlas-based clustering, as well as diffusion tractography-based parcellation, can be useful in estimating the stimulation target (“sweet spot”) for STN-DBS in PD patients. Atlas-based as well as diffusion-based clustering might become a useful tool in DBS trajectory planning.

Background: Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk factors correlating with a tracheostomy, as well as the impact of an early tracheostomy on ventilation time and ICU length of stay (LOS) in MC. Methods: Retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015 to assess demographic/diagnostic data, rates and timing of tracheostomy and outcome. Results: In 107 out of 215 MC (49.8%), a tracheostomy was performed. Patients without tracheostomy were more likely to have an early-onset myasthenia gravis (27 [25.2%] vs 12 [11.5%], p = 0.01). Patients receiving a tracheostomy, however, were more frequently suffering from multiple comorbidities (20 [18.7%] vs 9 [8.3%], p = 0.03) and also the ventilation time (34.4 days ± 27.7 versus 7.9 ± 7.8, p < 0.0001) and ICU-LOS (34.8 days ± 25.5 versus 12.1 ± 8.0, p < 0.0001) was significantly longer than in non-tracheostomized patients. Demographics and characteristics of the course of the disease up to the crisis were not significantly different between patients with an early (within 10 days) compared to a late tracheostomy. However, an early tracheostomy correlated with a shorter duration of MV at ICU (26.2 days ± 18.1 versus 42.0 ± 33.1, p = 0.006), and ICU-LOS (26.2 days ± 14.6 versus 42.3 ± 33.0, p = 0.003). Conclusion: Half of the ventilated patients with MC required a tracheostomy. Poorer health condition before the crisis and late-onset MG were associated with a tracheostomy. An early tracheostomy (≤ day 10), however, was associated with a shorter duration of MV and ICU-LOS by 2 weeks.

Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Muscle-specific kinase-antibodies (MuSK-ABs) are detected in ~ 6% of MG, but data on outcome of MuSK-MCs are still lacking. We made a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody positive MG (AchR-MG) or MuSK-MG between 2006 and 2015 in a retrospective German multicenter study. We identified 19 MuSK-AB associated MCs in 15 patients and 161 MCs in 144 patients with AchR-ABs only. In contrast to patients with AchR-AB, MuSK-AB patients were more often female (p = 0.05, OR = 2.74) and classified as Myasthenia Gravis Foundation of America-class IV before crisis (p = 0.04, OR = 3.25). MuSK-AB patients suffer more often from multiple chronic disease (p = 0.016, OR = 4.87) and were treated more invasively in terms of plasma exchanging therapies (not significant). The number of days of mechanical ventilation (MV) (43.0 ± 53.1 vs. 17.4 ± 18; p p p

OBJECTIVE Parkinson's Disease (PD) is a progressive neurodegenerative disorder, manifesting with subtle early signs, which often hinder timely and early diagnosis and treatment. The development of accessible, technology-based methods for longitudinal PD symptoms tracking in daily living offers the potential for transforming the disease assessment and accelerating PD diagnosis. METHODS A privacy-aware method for classifying PD patients and healthy controls (HC), on the grounds of speech impairment present in PD, is proposed here. Voice features from running speech signals were extracted from recordings passively captured over voice phone calls. Features are fed in a language-aware training of multiple- and single-instance learning classifiers, along with demographic variables, exploiting a multilingual cohort of 498 subjects (392/106 self-reported HC/PD patients) to classify PD. RESULTS By means of leave-one-subject-out cross-validation, the best-performing models yielded 0.69/0.68/0.63/0.83 area under the Receiver Operating Characteristic curve (AUC) for the binary classification of PD patient vs. HC in sub-cohorts of English/Greek/German/Portuguese-speaking subjects, respectively. Out-of-sample testing of the best performing models was conducted in an additional dataset, generated by 63 clinically-assessed subjects (24/39 HC/early PD patients). Testing has resulted in 0.84/0.93/0.83 AUC for the English/Greek/German-speaking sub-cohorts, respectively. Comparative analysis with other approaches for language-aware PD detection justified the efficiency of the proposed one, considering the ecological validity of the acquired voice data. CONCLUSIONS The present work demonstrates increased robustness in PD detection using voice data captured in-the-wild. SIGNIFICANCE A high-frequency, privacy-aware and unobtrusive PD screening tool is introduced for the first time, based on analysis of voice samples captured during routine phone calls.

Background: We assessed whether detection of stroke underlying acute vertigo using HINTS plus (head-impulse test, nystagmus type, test of skew, hearing loss) can be improved by video-oculography for automated head-impulse test (V-HIT) analysis. Methods: We evaluated patients with acute vestibular syndrome (AVS) presenting to the emergency room using HINTS plus and V-HIT-assisted HINTS plus in a randomized sequence followed by cranial MRI and caloric testing. Image-confirmed posterior circulation stroke or vertebrobasilar TIA were the reference standards to calculate diagnostic accuracy. We repeated statistical analysis for a third protocol that was composed post hoc by replacing the head-impulse test with caloric testing in the HINTS plus protocol. Results: We included 30 AVS patients (ages 55.4 ± 17.2 years, 14 females). Of these, 11 (36.7%) had posterior circulation stroke (n = 4) or TIA (n = 7). Acute V-HIT-assisted HINTS plus was feasible and displayed tendentially higher accuracy than conventional HINTS plus (sensitivity: 81.8%, 95% CI 48.2–97.7%, specificity 31.6%, 95% CI 12.6–56.6% vs. sensitivity 72.7%, 95% CI 39.0–94.0%, specificity 36.8%, 95% CI 16.3–61.6%). The new caloric-supported algorithm showed high accuracy (sensitivity 100%, 95% CI 66.4–100%, specificity 66.7%, 95% CI 41–86.7%). Conclusions: Our study provides pilot data on V-HIT-assisted HINTS plus for acute AVS assessment and indicates the diagnostic value of integrated acute caloric testing.

Background Non‐motor symptoms (NMS) are integral to Parkinson's Disease (PD) and management remains a challenge. Safinamide is a novel molecule in relation to addressing NMS due to its multifocal mechanism of action with both dopaminergic and non‐dopaminergic properties. Objective To investigate the efficacy of safinamide on NMS and its burden in PD patients with motor fluctuations after 6 months of treatment. Methods This observational, multicenter, open‐label, pilot study assessed a wide range of NMS using the following rating scales, NMSS (non‐motor symptom scale), KPPS (King's PD pain scale), HADS (hospital anxiety and depression scale), PDQ‐8 (Parkinson's disease quality of life questionnaire), and PDSS‐2 (Parkinson's disease sleep scale), EuroQol‐5D 3 level version (EQ‐5D‐3L), CGI‐I (clinical global impression of improvement), and PGI‐C (patient global impression of change). Motor examination using UPDRS part III (Unified Parkinson's disease rating scale, motor examination), UPDRS IV (complications of therapy) and Hoehn and Yahr staging were also obtained. Results 27 patients were included in the analysis and were evaluated at baseline and ≥ 6 months after safinamide treatment. 26 patients had a daily maintenance dose of 100 mg and 1 patient a daily dose of 50 mg. Significant improvements in UPDRS IV, KPPS item 5 (region‐specific “off” dystonia), KPPS domain 3 (items 4–6, fluctuation related pain) and KPPS total score were observed after treatment with safinamide, while maintaining stable dopaminergic medication. No statistically significant differences were found in NMSS, HADS, PDSS‐2, EQ‐5D‐3L, and PDQ‐8 after treatment. Conclusions Our results suggest that safinamide may have a beneficial effect on pain, a key unmet need in fluctuating PD patients., In this observational prospective study we investigate the effects of safinamide on non‐motor symptoms in patients with fluctuating Parkinson's disease. Our main finding is a significant improvement in UPDRS IV and pain as measured by the KPPS.

We aimed to assess how evidence-based stroke care changed over the two waves of the COVID-19 pandemic. We analyzed acute stroke patients admitted to a tertiary care hospital in Germany during the first (2 March 2020–9 June 2020) and second (23 September 2020–31 December 2020, 100 days each) infection waves. Stroke care performance indicators were compared among waves. A 25.2% decline of acute stroke admissions was noted during the second (n = 249) compared with the first (n = 333) wave of the pandemic. Patients were more frequently tested SARS-CoV-2 positive during the second than the first wave (11 (4.4%) vs. 0; p < 0.001). There were no differences in rates of reperfusion therapies (37% vs. 36.5%; p = 1.0) or treatment process times (p > 0.05). However, stroke unit access was more frequently delayed (17 (6.8%) vs. 5 (1.5%); p = 0.001), and hospitalization until inpatient rehabilitation was longer (20 (1, 27) vs. 12 (8, 17) days; p < 0.0001) during the second compared with the first pandemic wave. Clinical severity, stroke etiology, appropriate secondary prevention medication, and discharge disposition were comparable among both waves. Infection control measures may adversely affect access to stroke unit care and extend hospitalization, while performance indicators of hyperacute stroke care seem to be untainted.

Although Gaucher disease can be accompanied by Lewy pathology (LP) and extrapyramidal symptoms, it is unknown if LP exists in Fabry disease (FD), another progressive multisystem lysosomal storage disorder. We aimed to elucidate the distribution patterns of FD-related inclusions and LP in the brain of a 58-year-old cognitively unimpaired male FD patient suffering from predominant hypokinesia. Immunohistochemistry (CD77, α-synuclein, collagen IV) and neuropathological staging were performed on 100-µm sections. Tissue from the enteric or peripheral nervous system was unavailable. As controls, a second cognitively unimpaired 50-year-old male FD patient without LP or motor symptoms and 3 age-matched individuals were examined. Inclusion body pathology was semiquantitatively evaluated. Although Lewy neurites/bodies were not present in the 50-year-old individual or in controls, severe neuronal loss in the substantia nigra pars compacta and LP corresponding to neuropathological stage 4 of Parkinson disease was seen in the 58-year-old FD patient. Major cerebrovascular lesions and/or additional pathologies were absent in this individual. We conclude that Lewy body disease with parkinsonism can occur within the context of FD. Further studies determining the frequencies of both inclusion pathologies in large autopsy-controlled FD cohorts could help clarify the implications of both lesions for disease pathogenesis, potential spreading mechanisms, and therapeutic interventions.

Endovascular therapy (EVT) trials enrolled ischemic stroke patients with good pre-stroke functional status. However, this information needed for rapid decision-making is commonly lacking in clinical practice. We hypothesized that initial misjudgment of pre-stroke functional status attenuates clinical outcomes of EVT. Data were derived from our prospective registry of ischemic stroke patients undergoing EVT for anterior circulation large vessel occlusion (01/2016–12/2017). Considering all information accumulated during hospital course, pre-stroke modified Rankin scale (mRS) was independently re-assessed and compared with pre-EVT assessments. Misjudgment was defined as any difference in mRS categories between first- and second-look assessments. Multivariable model was built to adjust for confounding variables of unfavorable outcome (mRS 3–6) and death at 90 days. Overall, we studied 217 patients: median age 75 years (IQR 64–81), 54% women, median NIHSS 17 (12–20) points. Second-look assessment of pre-stroke mRS revealed 73 (34%) cases initially being misjudged by ≥ 1 category and 17 (8%) by ≥ 2 categories. None of the second-look mRS assessments resulted in a lower mRS category than initially rated. Patients whose pre-stroke mRS score was misjudged prior to EVT showed more frequently unfavorable outcome (62/73 [84.9%] vs. 94/144 [65.3%], p = 0.002) or were deceased (30/73 [41.1%] vs. 25/144 [17.4%], p

ObjectiveTo determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH.MethodsRetrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC.ResultsIHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04–1.93) vs non-LDSH: 1.32 (0.33–3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38–4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4–6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume ConclusionsHeparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.

BACKGROUND AND PURPOSE Hypothermia may be neuroprotective in acute ischemic stroke. Patients with anterior circulation large vessel occlusion (acLVO) are frequently hypothermic after endovascular therapy (EVT). We sought to determine whether this inadvertent hypothermia is associated with improved outcome. METHODS We extracted data of consecutive patients (January 2016 to May 2019) who received EVT for acLVO from our prospective EVT register of all patients screened for EVT at our tertiary stroke center. We assessed functional outcome at 3 months and performed multivariate analysis to calculate adjusted risk ratios (aRRs) for favorable outcome (modified Rankin Scale scores = 0-2) and mortality across patients who were hypothermic (

Introduction: Our goal was to investigate whether biomarkers of cerebral damage are found in autoimmune-mediated epilepsy (AIE) and whether these can differentiate AIE from other seizure disorders.Methods: We retrospectively searched our cerebrospinal fluid (CSF) database for patients with definite AIE, hippocampal sclerosis due to other causes (HS), genetic generalized epilepsy (GGE), and psychogenic, non-epileptic seizures (PNES). We measured serum and CSF tau, neurofilament 1 (NFL), glial fibrillary acid protein (GFAP), and ubiquitin-carboxy-terminal hydrolase L1 with a single-molecule array.Results: We identified suitable samples from patients with AIE (n = 13) with different antibodies and compared them to HS (n = 13), GGE (n = 7), and PNES (n = 8). The NFL levels were significantly elevated in the serum (p = 0.0009) and CSF (p < 0.0019) of AIE patients. The AIE group was significantly older, while the disease duration was significantly shorter than in the control groups. NFL correlated significantly with age in all groups, and the NFL levels of AIE patients were hardly higher than those of healthy elderly people published elsewhere.Conclusions: Our data indicate that the elevated NFL levels in AIE patients are most likely due to the higher age in this group and not due to the underlying inflammation. Unless larger prospective studies with intra-individual, longitudinal analyses and treatment responses would contradict our findings, NFL in serum might yet become a biomarker for disease activity and differential diagnosis.

Introduction: Recent studies linked coronavirus disease 2019 (COVID-19) to thromboembolic complications likely mediated by increased blood coagulability and inflammatory endothelial impairment. Objective: We aimed to assess the risk of acute stroke in patients with COVID-19 related to clinical severity of the disease. Methods: We conducted an observational multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we performed a systematic review using PubMed/MEDLINE, EMBASE, Cochrane Library and bibliographies of identified articles following PRISMA guidelines including data from observational studies of acute stroke in COVID-19 patients. Data was extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RR) and 95% confidence intervals (95%CIs) for acute stroke related to COVID-19 severity using random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I 2 -statistics. PROSPERO identifier : CRD42020187194. Results: Of 165 patients hospitalized for COVID-19 (49.1% males, median age 67 [57-79], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95%CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Among 741 pooled COVID-19 patients overall stroke rate was 2.9% (95%CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR 4.12, 95%CI 1.7-10.25; p=0.002) with no evidence of heterogeneity (I 2 =0%, p=0.82). Conclusions: Synthesized analysis of data from our multicenter study and previously published cohorts demonstrate that severity of COVID-19 is associated with an increased risk of acute stroke, underscoring the necessity of neurological monitoring in patients infected with SARS-CoV-2.

Parkinson’s disease (PD) is a neurodegenerative disorder with both motor and non-motor symptoms. Despite the progressive nature of PD, early diagnosis, tracking the disease’s natural history and measuring the drug response are factors that play a major role in determining the quality of life of the affected individual. Apart from the common motor symptoms, i.e., tremor at rest, rigidity and bradykinesia, studies suggest that PD is associated with disturbances in eating behavior and energy intake. Specifically, PD is associated with drug-induced impulsive eating disorders such as binge eating, appetite-related non-motor issues such as weight loss and/or gain as well as dysphagia—factors that correlate with difficulties in completing day-to-day eating-related tasks. In this work we introduce Plate-to-Mouth (PtM), an indicator that relates with the time spent for the hand operating the utensil to transfer a quantity of food from the plate into the mouth during the course of a meal. We propose a two-step approach towards the objective calculation of PtM. Initially, we use the 3D acceleration and orientation velocity signals from an off-the-shelf smartwatch to detect the bite moments and upwards wrist micromovements that occur during a meal session. Afterwards, we process the upwards hand micromovements that appear prior to every detected bite during the meal in order to estimate the bite’s PtM duration. Finally, we use a density-based scheme to estimate the PtM durations distribution and form the in-meal eating behavior profile of the subject. In the results section, we provide validation for every step of the process independently, as well as showcase our findings using a total of three datasets, one collected in a controlled clinical setting using standardized meals (with a total of 28 meal sessions from 7 Healthy Controls (HC) and 21 PD patients) and two collected in-the-wild under free living conditions (37 meals from 4 HC/10 PD patients and 629 meals from 3 HC/3 PD patients, respectively). Experimental results reveal an Area Under the Curve (AUC) of 0.748 for the clinical dataset and 0.775/1.000 for the in-the-wild datasets towards the classification of in-meal eating behavior profiles to the PD or HC group. This is the first work that attempts to use wearable Inertial Measurement Unit (IMU) sensor data, collected both in clinical and in-the-wild settings, towards the extraction of an objective eating behavior indicator for PD.

Objective To investigate diagnostic accuracy of a nerve ultrasound (US) protocol that is individualized to a patient’s clinical deficits for the differentiation of amyotrophic lateral sclerosis with predominant lower motoneuron disease (ALS/LMND) and multifocal motor neuropathy (MMN). Methods Single-center, prospective, examiner-blinded, diagnostic study in two cohorts. Cohort I (model development): Convenience sample of subjects with ALS/LMND or MMN according to revised El-Escorial or EFNS guidelines. Cohort II (model validation): Consecutively recruited treatment-naïve subjects with suspected diagnosis of ALS/LMND or MMN. Cutoffs for 28 different US values were determined by Receiver Operating Curve (ROC) in cohort I. Area Under The Curve (AUC) of US was compared to nerve conduction studies (NCS). Diagnostic accuracy of US protocols, individualized according to clinical deficits, was compared to former rigid non-individualized protocols and to random examination site selection in cohort II. Results 48 patients were recruited. In cohort I (28 patients), US had higher ROC AUCs than NCS, US 0.82 (0.12) (mean (standard deviation)), NCS (compound muscle action potential (CMAP) 0.60 (0.09), p t-test). US models based on the nerve innervating the clinically most affected muscles had higher correct classification rates (CCRs, 93%) in cohort II than former rigid protocols (85% and 80%), or models with random measurement site selection (66% and 80%). Conclusions Clinically guided US protocols for differentiation of ALS/LMND from MMN increase diagnostic accuracy when compared to clinically unguided protocols. They also require less measurements sites to achieve this accuracy.

To assess the kidney safety profile of mannitol in patients with malignant middle cerebral artery (MCA) infarction.We studied consecutive patients with malignant MCA infarction (01/2008-01/2018). Malignant MCA infarction was defined according to DESTINY criteria. We compared clinical endpoints including acute kidney injury (AKI; according to Kidney Disease: Improving Global Outcomes [KDIGO]) and dialysis between patients with and without mannitol. Multivariable model was built to explore predictor variables of AKI and in-hospital death.Overall, 219 patients with malignant MCA infarction were included. Mannitol was administered in 93/219 (42.5%) patients with an average dosage of 650 g (250-950 g). Patients treated with mannitol more frequently suffered from AKI (39.8% vs. 11.9%; p 0.001) and required hemodialysis (7.5% vs. 0.8%; p = 0.01) than patients without mannitol. At discharge, more patients in the mannitol group had persistent AKI than control patients (23.7% vs. 6.4%, p 0.001). In multivariable model, mannitol emerged as independent predictor of AKI (OR 5.02, 95%CI 2.36-10.69; p 0.001).Acute kidney injury appears to be a frequent complication of hyperosmolar therapy with mannitol in patients with malignant MCA infarction. Given the lack of evidence supporting effectiveness of mannitol in these patients, its routine use should be carefully considered.

Parkinson’s disease (PD) is known to involve the peripheral nervous system (PNS) and the enteric nervous system (ENS). Functional changes in PNS and ENS appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients like constipation, that can precede the appearance of motor symptoms by years. We have shown that environmental toxins can trigger the disease by acting on the ENS and on the autonomic nervous system. Oral exposure to the pesticide rotenone, a mitochondrial Complex I inhibitor, leads to decreased stool depositions in mice. Here we analyzed the effect of rotenone on the function and structure of the ENS by measuring intestinal contractility in a tissue bath and by analyzing related protein expression. Our results show that rotenone changes the normal physiological response of the intestine to carbachol, dopamine and electric field stimulation. The magnitude and direction of these alterations varies between intestinal regions and exposure times and is associated with an early up-regulation of dopaminergic, cholinergic and adrenergic receptors and an irregular reduction in the amount of enteric neurons in rotenone-exposed mice. The early appearance of these alterations makes them ideal candidates to be used as biomarkers for the detection of Parkinson’s disease in its early stages.

Highlights • Despite rigorous universal testing in a protected code stroke protocol, none of the consecutive 116 stroke patients tested were positive for SARS-CoV-2. • Universal testing did not adversely affect hyperacute stroke care. • Information on SARS-CoV-2 status can be used to guide protective measures in patients with acute stroke., Objective Stroke patients are thought to be at increased risk of Coronavirus Disease 2019 (COVID-19). To evaluate yield of universal laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute stroke patients and its impact on hyperacute stroke care. Methods Between weeks 14 and 18 in 2020, a protected code stroke protocol including infection control screening and laboratory testing for SARS-CoV-2 was prospectively implemented for all code stroke patients upon arrival to the emergency department. If infection control screen was positive, patients received protective hygienic measures and laboratory test results were available within four hours from testing. In patients with negative screen, laboratory results were available no later than the next working day. Door-to-imaging times of patients treated with thrombolysis or thrombectomy were compared with those of patients treated during the preceding weeks 1 to 13 in 2020. Results During the 4-weeks study period, 116 consecutive code stroke patients underwent infection control screen and laboratory testing for SARS-CoV-2. Among 5 (4.3%) patients whose infection control screen was positive, no patient was tested positive for SARS-CoV-2. All patients with negative infection control screens had negative test results. Door-to-imaging times of patients treated with thrombolysis and/or thrombectomy were not different to those treated during the preceding weeks (12 [9-15] min versus 13 [11-17] min, p = 0.24). Conclusions Universal laboratory testing for SARS-CoV-2 provided useful information on patients’ infection status and its implementation into a protected code stroke protocol did not adversely affect hyperacute stroke care.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder with the non-motor symptoms preceding the motor impairment that is needed for clinical diagnosis. In the current study, an angle-based analysis that processes activity data during sleep from a smartwatch for quantification of sleep quality, when applied on controls and PD patients, is proposed. Initially, changes in their arm angle due to activity are captured from the smartwatch triaxial accelerometry data and used for the estimation of the corresponding binary state (awake/sleep). Then, sleep metrics (i.e., sleep efficiency index, total sleep time, sleep fragmentation index, sleep onset latency, and wake after sleep onset) are computed and used for the discrimination between controls and PD patients. A process of validation of the proposed approach when compared with the PSG-based ground truth in an in-the-clinic setting, resulted in comparable state estimation. Moreover, data from 15 early PD patients and 11 healthy controls were used as a test set, including 1,376 valid sleep recordings in-the-wild setting. The univariate analysis of the extracted sleep metrics achieved up to 0.77 AUC in early PD patients vs. healthy controls classification and exhibited a statistically significant correlation (up to 0.46) with the clinical PD Sleep Scale 2 counterpart Items. The findings of the proposed method show the potentiality to capture non-motor behavior from users' nocturnal activity to detect PD in the early stage.

Fine-motor impairment (FMI) is progressively expressed in early Parkinson’s Disease (PD) patients and is now known to be evident in the immediate prodromal stage of the condition. The clinical techniques for detecting FMI may not be robust enough and here, we show that the subtle FMI of early PD patients can be effectively estimated from the analysis of natural smartphone touchscreen typing via deep learning networks, trained in stages of initialization and fine-tuning. In a validation dataset of 36,000 typing sessions from 39 subjects (17 healthy/22 PD patients with medically validated UPDRS Part III single-item scores), the proposed approach achieved values of area under the receiver operating characteristic curve (AUC) of 0.89 (95% confidence interval: 0.80–0.96) with sensitivity/specificity: 0.90/0.83. The derived estimations result in statistically significant ($$p p < 0.05 ) correlation of 0.66/0.73/0.58 with the clinical standard UPDRS Part III items 22/23/31, respectively. Further validation analysis on 9 de novo PD patients vs. 17 healthy controls classification resulted in AUC of 0.97 (0.93–1.00) with 0.93/0.90. For 253 remote study participants, with self-reported health status providing 252.000 typing sessions via a touchscreen typing data acquisition mobile app (iPrognosis), the proposed approach predicted 0.79 AUC (0.66–0.91) with 0.76/0.71. Remote and unobtrusive screening of subtle FMI via natural smartphone usage, may assist in consolidating early and accurate diagnosis of PD.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease, associated, among others, with motor symptoms such as resting tremor, rigidity and bradykinesia. At the same time, early diagnosis of PD is hindered by a high misdiagnosis rate and the subjective nature of the diagnosis process itself. Recent developments in mobile and wearable devices, such as smartphones and smartwatches, have allowed the automated detection and objective measurement of PD symptoms. In this paper we investigate the hypothesis that PD motor symptom degradation can be assessed by studying the in-meal behavior and modeling the food intake process. To achieve this, we use the inertial data from a commercial smartwatch to investigate the in-meal eating behavior of healthy controls and PD patients. In addition, we define and provide a methodology for calculating Plate-to-Mouth (PtM), an indicator that relates with the average time that the hand spends transferring food from the plate towards the mouth during the course of a meal. The presented experimental results, using our collected dataset of 28 participants (7 healthy controls and 21 PD patients), support our hypothesis. Results initially point out that PD patients have a higher PtM value than the healthy controls. Finally, using PtM we achieve a precision/recall/F1 of 0.882/0.714/0.789 towards classifying the meals from the PD patients and healthy controls.

Parkinson’s disease (PD) is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity, and when these symptoms respond to dopaminergic medications. Yet in the last years there was a greater recognition of additional aspects of the disease including non-motor symptoms and prodromal states with associated pathology in various regions of the nervous system. In this review we discuss current concepts of two major alterations found during the course of the disease: cytoplasmic aggregates of the protein α-synuclein and the degeneration of dopaminergic neurons. We provide an overview of new approaches in this field based on current concepts and latest literature. In many areas, translational research on PD has advanced the understanding of the disease but there is still a need for more effective therapeutic options based on the insights into the basic biological phenomena.

It has been debated for decades whether single, self-limited seizures damage cerebral cells. Meanwhile, very sensitive measurements of biomarkers have become available, i.e. tau, neurofilament protein light (NFL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxyterminate hydrolase L1 (UCHL-1), which we explored in this study.Adult patients of the epilepsy monitoring unit were admitted to the study after written consent. Blood samples were drawn at baseline, immediately after a TCS and after two, six and 24 h. The markers were measured from frozen samples with a single-molecule array (SIMOA).20 patients and 20 seizures were included. All markers showed subtle but significant postictal increases and returned to normal within the next few hours (p 0.05). An increase of at least 100 % from baseline was noted in 30 % of patients for tau, 25 % for UCHL-1 and 15 % for GFAP, while NFL levels never increased above 100 %. Lactate was slightly correlated with the tau increase (r = 0.47, p = 0.037), leukocytes were correlated with postictal changes of GFAP (r = 0.68 p = 0.001).Our data supports the assumption that significant cerebral stress occurs in some but not all self-limited TCS. The postictal inflammatory response in particular seems to play an important role.

Although olfactory dysfunction is one of the most well-established prodromal symptoms in Parkinson's disease (PD), its correlation with clinical disease progression or dopaminergic dysfunction still remains unclear. We here evaluated the association of striatal dopamine metabolism and olfactory function in a homogenous cohort of 30 patients with early untreated de novo PD. Striatal dopamine metabolism was assessed by the extended 18Fluorodopa PET scanning protocol to measure 18Fluorodopa uptake (Kocc) and the effective dopamine distribution volume ratio (EDVR) as the inverse of dopamine turnover. Olfactory function was estimated by the 'Sniffin' Sticks' test including odor threshold (T), discrimination (D) and identification (I) assessment. We detected moderate correlations of the EDVR in the posterior putamen with the TDI composite score (r = 0.412; p = 0.024; Pearson's correlation test) and the odor identification score (r = 0.444; p = 0.014). These correlations were confirmed by multivariate regression analyses using age, sex, symptom duration and disease severity as measured by UPDRSIII motor score as candidate covariates. No other associations were observed between olfaction measures and Kocc and EDVR in all striatal regions. Together, olfactory dysfunction in early PD is not correlated with striatal 18Fluorodopa uptake as a measure for dopaminergic degeneration, but with putaminal dopamine turnover as a marker for dopaminergic presynaptic compensatory processes in early PD. These results should be treated as hypothesis generating and require confirmation by larger multicenter studies.

Current therapeutic approaches to Alzheimer disease (AD) remain disappointing and, hence, there is an urgent need for effective treatments. Here, we provide a perspective review on the emerging role of "metabolic inflammation" and stress as a key factor in the pathogenesis of AD and propose a novel rationale for correction of metabolic inflammation, increase resilience and potentially slow-down or halt the progression of the neurodegenerative process. Based on recent evidence and observations of an early pilot trial, we posit a potential use of extracorporeal apheresis in the prevention and treatment of AD. Apolipoprotein E, lipoprotein(a), oxidized LDL (low density lipoprotein)'s and large LDL particles, as well as other proinflammatory lipids and stress hormones such as cortisol, have been recognized as key factors in amyloid plaque formation and aggravation of AD. Extracorporeal lipoprotein apheresis systems employ well-established, powerful methods to provide an acute, reliable 60-80% reduction in the circulating concentration of these lipid classes and reduce acute cortisol levels. Following a double-membrane extracorporeal apheresis in patients with AD, there was a significant reduction of proinflammatory lipids, circulating cytokines, immune complexes, proinflammatory metals and toxic chaperones in patients with AD. On the basis of the above, we suggest designing clinical trials to assess the promising potential of such "cerebropheresis" treatment in patients with AD and, possibly, other neurodegenerative diseases.

Parkinson's disease (PD) was first described by the English physician James Parkinson in his work An Essay on the Shaking Palsy in 1817. This correlates well with the beginning of the industrial and chemical revolution in Europe during the late 18th and 19th centuries. This period and the time afterward are linked to the increased production and use of chemicals and pesticides. In this chapter, we review (1) the epidemiological evidence linking the appearance of PD to an increase in exposure to environmental toxins, and (2) the possible mechanisms underlying this correlation obtained from in vitro and in vivo experimental studies.

Decompressive hemicraniectomy improves survival rates and functional outcome in patients with space-occupying middle cerebral artery (MCA) infarction. We sought to determine clinical outcomes in elderly patients with MCA infarction treated with hemicraniectomy and to identify factors associated with functional outcome. We performed a prospective, single-center observational study aiming to include patients aged ≥ 61 years with large MCA infarction treated with hemicraniectomy. The primary endpoint was the functional outcome according to modified Rankin Scale (mRS) score at 6 months after hemicraniectomy. Secondary endpoints included outcome measures at 12 months. A pooled analysis of individual patient data from the single-center cohort and a DESTINY 2 trial subgroup was performed to identify factors associated with functional status at 12 months. We included 40 MCA infarction patients who underwent hemicraniectomy between 2012 and 2017 at our university hospital (median [IQR] patient age 64 [62–67] years, National Institutes of Health Stroke Scale score 17 [16–21]). The dominant hemisphere was affected in 22/40 patients. Hemicraniectomy was performed within 31 [23–53] h of symptom onset. At 6 months after hemicraniectomy, 6/40 patients (15%) were moderately or moderately severely disabled (mRS score 3 or 4), 19 (47.5%) severely disabled (mRS score 5), and 15 (37.5%) had died. Compared to surgically treated DESTINY 2 patients, the single-center patients less likely exhibited favorable functional outcome at 6 months (mRS scores 0–4; odds ratio 0.239 [95% CI 0.082–0.696]). Case-fatality rate at 12 months was 43%. In a pooled analysis including 79 patients from DECAP and DESTINY 2, no significant associations of baseline and treatment factors with the clinical status at 12 months were observed. In this single-center cohort of elderly patients with space-occupying MCA infarction and decompressive hemicraniectomy, the probability for survival without severe disability was low. Lethality at 6 and 12 months was comparable to previously reported data from a randomized trial.

ZusammenfassungSchmerzen beim idiopathischen Parkinsonsyndrom (IPS) treten bei 40 %–95 % der Patienten auf und beeinträchtigen die Lebensqualität, sind jedoch oftmals unterdiagnostiziert und werden nur unsystematisch therapiert.Schmerzätiologie und Schmerzcharakter können sehr vielfältig sein und obwohl die Optimierung der Parkinson-Medikation die Basis der Schmerzbehandlung ist, sind in den meisten Fällen zusätzliche Therapien zur suffizienten Behandlung der Schmerzen notwendig.In dieser Arbeit werden Epidemiologie und Pathophysiologie des Schmerzes beim IPS dargestellt sowie Schmerzcharakteristika beschrieben. Es wird aufgezeigt, welche Methoden der Schmerzbehandlung beim IPS genutzt werden und wie Patienten die Effektivität der Therapien beurteilen. Auf Basis der begrenzten Datenlage und eines Expertenkonsens wurden praxisrelevante Vorschläge zu Diagnostik und Therapie bei Schmerz und IPS gegeben.Diese Arbeit soll dazu beitragen, Neurologen für das Thema Schmerz beim IPS zu sensibilisieren. Aufgrund der Komplexität und Besonderheiten der neurodegenerativen Erkrankung sollten Neurologen an der interdisziplinären Schmerztherapie beim IPS beteiligt sein und ihren Patienten differenziertere Therapieoptionen bereitstellen als bisher.

ZusammenfassungDie erfolgreiche Haltungskontrolle setzt eine effektive und effiziente Interaktion aller posturalen Systeme voraus, die sowohl aktiv als auch reaktiv mittels muskulärer Kräfte den Körper im Gleichgewicht halten. Eine Störung dieses komplexen Posturalsystems auf sensorischer, zentraler oder motorischer Ebene führt in der Folge zu einer zunehmenden Instabilität und zu einer erhöhten Sturzneigung. Insofern scheinen die zuverlässige Erhebung der posturalen Kontrolle und die damit verbundene Sturzprävalenz ein wichtiges Element der ambulanten und stationären Versorgung zu sein. Die motorisch-funktionellen Assessments, die sich aus verschiedenen Gleichgewichts- und Stabilitätsaufgaben ergeben, stellen noch immer den Goldstandard zur Quantifizierung der posturalen Kontrolle dar. Diese Verfahren sind jedoch oftmals nicht in der Lage, die Gleichgewichtsfähigkeit eines Patienten vollumfänglich abzubilden, oder sind aufgrund der subjektiven Bewertung oder unzureichender Standardisierung nur bedingt vergleichbar. Das Ziel der vorliegenden Studie war daher die Entwicklung eines quantitativen Messverfahrens zur Überprüfung der posturalen Kontrolle, basierend auf dem neuroorthopädischen Therapiegerät Posturomed®. Das Messsystem wurde in Form eines reaktiven Screeningverfahrens ausgeführt. Bei diesem werden mechanische Perturbationen erzeugt mittels Elektromagneten, die an der Unterstützungsfläche des Probanden appliziert werden. Der Eignungsnachweis dieses Systems für eine Quantifizierung der posturalen Kontrolle erfolgte durch eine zweiarmige Querschnittsstudie mit 115 gesunden Probanden (Referenzgruppe) und 149 neurologischen Patienten.Die Gruppe der neurologischen Patienten setzte sich zusammen aus– 69 Patienten mit zerebraler Mikroangiopathie (ZMA) mit in den letzten 12 Monaten klinisch eher leichter, aber chronisch progredienter Symptomatik,– 31 Patienten mit Morbus Parkinson Stadium I bis III nach Hoehn & Yahr als chronisch progrediente, multilokuläre Netzwerkerkrankung und – 49 Patienten mit klinisch vordergründig restierender Hemiparese bei Zustand nach zerebraler Embolie (Kraftgrad des betroffenen Beins 4/5 oder latente Parese) außerhalb der Subakutphase. Die Ergebnisse der Studie belegen, dass Perturbationsversuche zur Quantifizierung der posturalen Kontrolle für ein breites Spektrum neurologischer Patienten geeignet sind. Die Validität des Verfahrens konnte durch eine hohe inhaltliche Übereinstimmung zwischen der dynamischen Posturografie und den konvergenten Maßen der Motorik (Berg Balance Scale; Dynamic Gait Index) nachgewiesen werden. Das vorgestellte System erscheint folglich geeignet, das reaktive Gleichgewicht als eine Eigenschaft der motorischen Standkontrolle zu bestimmen. Die dynamische Posturografie auf Basis eines Perturbationsversuchs kann im klinischen und therapeutischen Umfeld zur Quantifizierung der posturalen Kontrolle eingesetzt werden. Zielgruppenlimitationen und damit verbundene Einschränkungen der Generalisierbarkeit von motorisch-funktionellen Testverfahren werden mit ihm überwunden. Darüber hinaus können auf der Basis der reaktiven posturalen Kompetenz individuelle Rückschlüsse auf das Sturzrisiko gezogen werden. Die Prognosegüte dieser Sturzrisikobewertung entspricht denen der motorisch-funktionellen Testverfahren und ist je nach Zielgruppe teilweise sogar besser. Für Patienten mit Morbus Parkinson konnte für den Dämpfungskoeffizienten bei einem Grenzwert von Δτ = − 0,45 s die höchste Güte ermittelt werden. Eine Sensitivität von 79 % und Spezifität von 78 % lassen eine gute Verwendung als sturzbezogenes Assessment erkennen. Der routinemäßige klinische Einsatz zur Quantifizierung der Sturzgefährdung, z. B. im Rahmen einer Krankenhausaufnahme, erscheint auf Grundlage der Ergebnisse empfehlenswert. Eine Grundvoraussetzung dafür, dass sich ein Assessment für eine Verlaufsbestimmung im Rahmen von Behandlungen einer Erkrankung eignet, ist seine ausreichende Reliabilität. Die laterale Perturbation und dann die Wertung von mittlerer Schwingungsgeschwindigkeit und Schwingungsdistanz sind geeignet für die Beurteilung der posturalen Stabilität im Verlauf neurologischer Erkrankungen und damit auch für eine quantitative Erfassung auftretender Therapieeffekte.

The German Society of Ultrasound in Medicine (DEGUM) recently revised its multiparametric criteria for duplex ultrasonography (DUS) grading of internal carotid artery (ICA) disease. We determined the diagnostic accuracy of the revised DEGUM criteria for ultrasonography grading of ICA disease in a prospective multicenter study. We evaluated consecutive patients who underwent digital subtraction angiography of the extracranial carotid arteries at four tertiary care hospitals. Blinded investigators graded ICA disease according to DEGUM-recommended ultrasonography criteria and calculated NASCET-type percent stenosis from angiography images. Endpoints included overall classification accuracy, prediction of clinically relevant disease categories and between-test agreement in the continuous range of percent stenosis. A total of 121 patients (median age: 69 [IQR, 16] years; 74 % men; median time between DUS and angiography: 1 day [IQR, 2]) provided 163 DUS-angiography carotid artery pairs. The classification accuracy of the DEGUM criteria to predict stenosis within 10 % increments as compared to angiography was 34.9 % (95 % CI, 28.0 - 42.6). The sensitivity of DUS for the detection of moderate (50 - 69 %) and severe (70 - 99 %) stenosis was 35 % and 81 %, with an overall accuracy of 73 % and 74 %, respectively. The specificity was 89 % and 69 %, respectively. Considering the continuous spectrum of the disease (0 - 100 %), the Bland-Altman interval limit of agreement was 51 %. At laboratories experienced with ultrasound grading of the extracranial ICA, the revised DEGUM multiparametric ultrasonography criteria do not eliminate the need for a confirmatory test for the identification of clinically relevant grades of the disease.ZIEL: Die multiparametrischen Ultraschallkriterien zur Graduierung von Karotisstenosen der Deutschen Gesellschaft für Ultraschall in der Medizin (DEGUM) wurden revidiert, bislang aber nicht mit dem Goldstandard Angiografie validiert. Ziel dieser prospektiven multizentrischen Validierungsstudie war es, die diagnostische Güte der DEGUM Ultraschallkriterien zu bestimmen. An vier Zentren wurden konsekutive Patienten eingeschlossen, bei denen routinemäßig eine digitale Subtraktionsangiografie (DSA) der extrakraniellen Arteria carotis interna (ACI) durchgeführt wurde. Die Graduierung des Stenosegrades der ACI erfolgte verblindet gemäß der multiparametrischen DEGUM Ultraschallkriterien. Angiografisch erfolgte die verblindete Stenosegraduierung entsprechend der NASCET Definition. Endpunkte umfassten die Gesamttrefferquote zur Vorhersage von Stenosen in vorgegebenen DEGUM Stenoseintervallen, Vorhersage von klinisch relevanten Stenosekategorien und diagnostische Übereinstimmung beider Methoden im kontinuierlichen Stenosebereich. Von insgesamt 121 rekrutierten Patienten (mittleres Alter, 69 [IQR, 16] Jahre, 74 % Männer, mediane Zeit zwischen Duplexsonografie und DSA, 1 Tag [IQR, 2]) ergaben sich 163 Duplex-DSA Gefäßpaare für die Validierung. Die Gesamttrefferquote der DEGUM-Ultraschallkriterien zur Vorhersage des Stenosegrades innerhalb von 10 % -Schritten im Vergleich zur DSA betrug 34,9 % (95 % CI, 28,0 – 42,6). Die Sensitivität der Ultraschallkriterien für den Nachweis von mittelgradigen (50 – 69 %) und hochgradigen (70 – 99 %) Stenosen betrug 35 % und 81 % mit einer Gesamtgenauigkeit von 73 % und 74 %. Die Spezifität betrug 89 % und 69 %. Der Bland-Altman-Übereinstimmungsbereich zwischen beiden Methoden betrug 51 %. In der Identifikation von klinisch relevanten Stenosekategorien der ACI beseitigen die multiparametrischen DEGUM Ultraschallkriterien nicht die Notwendigkeit eines vaskulären Bestätigungstestes.

Introduction Individuals with unexplained smell loss constitute an at-risk population for the development of Parkinson's disease (PD). Currently, no specific MRI patterns are known for early PD diagnosis. In this study, we measured the fractional anisotropy (FA) in the substantia nigra (SN) in PD patients, in patients with idiopathic smell loss, and in healthy controls. Methods All subjects underwent extensive olfactory testing and MR imaging data were obtained to explore SN diffusion characteristics. The SN regions were manually identified by two independent raters on the individual imaging data. Results FA measurements in the SN revealed significant group differences, with reduced values clearly distinguishing PD patients and patients with idiopathic smell loss from healthy controls. Conclusion These findings indicate a reduced intrinsic integrity of the SN in PD at-risk subjects and support the risk status of patients with idiopathic smell loss.

Advanced Parkinson's disease is characterized by the presence of motor fluctuations, various degree of dyskinesia, and disability with functional impact on activities of daily living and independence. Therapeutic management aims to extend levodopa benefit while minimizing motor complications and includes, in selected cases, the implementation of drug infusion and surgical techniques. In milder forms of motor complications, these can often be controlled with manipulation of levodopa dose and the introduction of supplemental therapies such as catechol-O-methyl transferase inhibitors, monoamine oxidase B inhibitors, and dopamine agonists including apomorphine. Clinical experience and evidence from published studies indicate that when these agents cannot satisfactorily control motor complications, patients should be assessed and considered for device-aided therapies. This review article summarizes some of the newer available therapeutic opportunities such as use of enzyme inhibitors like opicapone and safinamide, adenosine A2A receptor antagonists, apomorphine and levodopa/carbidopa intestinal gel infusion, deep brain stimulation including the role of closed-loop and adaptive stimulation, and MRI-guided focused ultrasound. © 2018 International Parkinson and Movement Disorder Society.

BACKGROUND AND PURPOSE The aim was to determine the predictors of focal hypoperfusion on computed tomography (CT) perfusion (CTP) in patients with acute posterior circulation stroke and its association with long-term outcome. METHODS Patients with posterior circulation stroke were selected from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) who underwent CTP within 24 h of stroke onset as part of the stroke imaging protocol. Hypoperfusion was defined as an area of visually well demarcated mean transit time prolongation corresponding to an arterial territory on standard reconstruction CTP imaging maps. Areas of hypoperfusion were assessed with the posterior circulation Acute Stroke Prognosis Early CT Score. Clinical and imaging associations with focal hypoperfusion were identified using multiple imputation analyses, and the adjusted functional outcome measured by the modified Rankin Scale at 3 and 12 months was determined. RESULTS Of the 3595 consecutive patients from the ASTRAL registry between 2003 and 2014, 1070 (29.7%) had a posterior circulation stroke and 436 of these (40.7%) patients had a good quality baseline CTP. 23.1% had early ischaemic changes and 37.4% had focal hypoperfusion. In multiple imputation analysis, visual field deficits, reduced level of consciousness, cardiac and multiple stroke mechanisms, significant vessel pathology and ischaemic changes visible on plain CT were associated with focal hypoperfusion. Focal hypoperfusion was independently associated with outcome at 12 months (odds ratio 2.04, 95% confidence interval 1.22-3.42, P

Building on social exchange and social identity theory, we examined how leader–member exchange (LMX) influences intention to report incidents in healthcare organizations through two different mechanisms. Using survey data of 15 hospitals in Germany ( N = 480) and multilevel structural equation modelling, we found as expected that LMX positively related to reporting-specific trust and organizational identification of employees. However, only reporting-specific trust but not organizational identification was directly related to incident reporting intention. Furthermore, top management support for patient safety moderated the link between LMX and reporting-specific trust, indicating a compensatory mechanism of top management support for followers with a low-quality leadership relationship. In addition, codification of patient safety regulations moderated the link between organizational identification and incident reporting intention. As expected, the institutionalization of patient safety norms through a strong follow-through of the organization is related to increased reporting only for employees with high organizational identification. Results are discussed in terms of how safety leadership can be enacted at both the supervisory and top management level in order to promote safety behaviour in healthcare organizations.