Neurological research and practice最新文献

Parkinson's disease (PD) is a neurodegenerative condition that is frequently associated with cognitive disorders. These can arise directly from the primary disease, or be triggered by external factors in susceptible individuals due to PD or other predisposing factors. The cognitive disorders encompass PD-associated cognitive impairment (PD-CI), delirium, PD treatment-associated cognitive side effects, cognitive non-motor fluctuations, and PD-associated psychosis. Accurate diagnosis of delirium is crucial because it often stems from an underlying disease that may be severe and require specific treatment. However, overlapping molecular mechanisms are thought to be involved in both delirium and PD, leading to similar clinical symptoms. Additionally, there is a bidirectional interaction between delirium and PD-CI, resulting in frequent concurrent processes that further complicate diagnosis. No reliable biomarker is currently available for delirium, and the diagnosis is primarily based on clinical criteria. However, the screening tools validated for diagnosing delirium in the general population have not been specifically validated for PD. Our review addresses the current challenges in the diagnosis of these cognitive disorders and highlights existing gaps within this field.

Background: The COVID-19 pandemic has affected acute stroke care, resulting in a decrease in stroke admissions worldwide. We examined trends in stroke severity at hospital admission, including (1) probable need for rehabilitation (National Institutes of Health Stroke Scale score > 6 points) and (2) probable need for assistance (modified Rankin Scale score > 2 points), and discharge to rehabilitation after acute care among inpatients with acute ischemic stroke and intracerebral hemorrhage.

Methods: We compared quality assurance data for acute ischemic stroke and intracerebral hemorrhage during the pandemic with the period before the pandemic in Hesse, Germany, using logistic regression analyses.

Results: Fewer inpatients with a probable need for rehabilitation were present at the beginning of the second wave of the COVID-19 pandemic in September 2020 (adjusted OR (aOR) 0.85, 95% CI [0.73, 0.99]), at the end of the second national lockdown in May 2021 (aOR 0.81, 95% CI [0.70, 0.94]), and at the approaching peak of COVID-19 wave 4 in November 2021 (aOR 0.79, 95% CI [0.68, 091]). Rates of probable need for assistance were significantly lower at the beginning of COVID-19 wave 2 in August 2020 (aOR 0.87, 95% CI [0.77, 0.99]) and at the beginning of COVID-19 wave 3 in March 2021 (aOR 0.80, 95% CI [0.71, 0.91]). Rates of discharge to rehabilitation were lower from the beginning in October 2020 to the peak of COVID-19 wave 2 in December 2020 (aOR 0.83, 95% CI [0.77, 0.90]), at the beginning and end of COVID-19 wave 3 in March 2021 and May 2021 (aOR 0.86, 95% CI [0.79, 0.92]), respectively, and at the beginning of COVID-19 wave 4 in October 2021 (aOR 0.86, 95% CI [0.76, 0.98]).

Conclusions: The results suggest that the COVID-19 pandemic had an impact on stroke management during the pandemic, but the absolute difference in stroke severity at hospital admission and discharge to rehabilitation was small.

Introduction: In Multiple Sclerosis (MS), patients´ characteristics and (bio)markers that reliably predict the individual disease prognosis at disease onset are lacking. Cohort studies allow a close follow-up of MS histories and a thorough phenotyping of patients. Therefore, a multicenter cohort study was initiated to implement a wide spectrum of data and (bio)markers in newly diagnosed patients.

Methods: ProVal-MS (Prospective study to validate a multidimensional decision score that predicts treatment outcome at 24 months in untreated patients with clinically isolated syndrome or early Relapsing-Remitting-MS) is a prospective cohort study in patients with clinically isolated syndrome (CIS) or Relapsing-Remitting (RR)-MS (McDonald 2017 criteria), diagnosed within the last two years, conducted at five academic centers in Southern Germany. The collection of clinical, laboratory, imaging, and paraclinical data as well as biosamples is harmonized across centers. The primary goal is to validate (discrimination and calibration) the previously published DIFUTURE MS-Treatment Decision score (MS-TDS). The score supports clinical decision-making regarding the options of early (within 6 months after study baseline) platform medication (Interferon beta, glatiramer acetate, dimethyl/diroximel fumarate, teriflunomide), or no immediate treatment (> 6 months after baseline) of patients with early RR-MS and CIS by predicting the probability of new or enlarging lesions in cerebral magnetic resonance images (MRIs) between 6 and 24 months. Further objectives are refining the MS-TDS score and providing data to identify new markers reflecting disease course and severity. The project also provides a technical evaluation of the ProVal-MS cohort within the IT-infrastructure of the DIFUTURE consortium (Data Integration for Future Medicine) and assesses the efficacy of the data sharing techniques developed.

Perspective: Clinical cohorts provide the infrastructure to discover and to validate relevant disease-specific findings. A successful validation of the MS-TDS will add a new clinical decision tool to the armamentarium of practicing MS neurologists from which newly diagnosed MS patients may take advantage. Trial registration ProVal-MS has been registered in the German Clinical Trials Register, `Deutsches Register Klinischer Studien` (DRKS)-ID: DRKS00014034, date of registration: 21 December 2018; https://drks.de/search/en/trial/DRKS00014034.

Background: Repetitive traumatic brain injuries in American football players (AFPs) can lead to the neurodegenerative disease chronic traumatic encephalopathy (CTE). Clinical symptoms of CTE range from mood and behavioral changes to cognitive impairment, depression, and suicidality. So far, CTE cannot be diagnosed in vivo and thus specific diagnostic parameters for CTE need to be found, to observe and treat exposed athletes as early as possible. Promising blood-based biomarkers for CTE include total tau (tTau), hyperphosphorylated tau (pTau), neurofilament light protein (NF-L), glial fibrillary acidic protein (GFAP), amyloid-β₄₀ (Aβ₄₀), amyloid-β₄₂ (Aβ₄₂) and calcium-binding protein B (S100-B). Previous studies have found elevated levels of these biomarkers in subjects exposed to TBIs, whereas cerebrospinal fluid (CSF) levels of Aβ₄₀ and Aβ₄₂ were decreased in CTE subjects. Here, we investigated whether young AFPs already exhibit changes of these biomarker candidates during the course of a single active season.

Methods: Blood samples were drawn from n = 18 American Football Players before and after a full season and n = 18 male age-matched control subjects. The plasma titers of tTau, pTau, NF-L, GFAP, Aβ₄₀, Aβ₄₂ and S100-B were determined. Additionally, Apathy, Depression, and Health status as well as the concussion history and medical care were assessed and analyzed for correlations.

Results: Here we show, that the selected biomarker candidates for CTE do not change significantly during the seven-month period of a single active season of American Football in blood samples of AFPs compared to healthy controls. But interestingly, they exhibit generally elevated pTau titers. Furthermore, we found correlations of depression, quality-of-life, career length, training participation and training continuation with headache after concussion with various titers.

Conclusion: Our data indicates, that changes of CTE marker candidates either occur slowly over several active seasons of American Football or are exclusively found in CSF. Nevertheless, our results underline the importance of a long-term assessment of these biomarker candidates, which might be possible through repeated blood biomarker monitoring in exposed athletes in the future.

Background: Novel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE.

Methods: A case of an adult patient with Lennox-Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search.

Results: Four case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases.

Conclusions: Based on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations.

Key points: We summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine. Refractory SE resolved after 4-7 days on fenfluramine. Swift fenfluramine up-titration was well-tolerated during SE treatment. Treatment-emergent adverse events on fenfluramine were not observed. Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox-Gastaut syndromes.

5q-associated spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are two distinct neurological disorders leading to degeneration of lower motor neurons. The antisense oligonucleotides (ASOs) nusinersen and tofersen are novel disease-modifying agents for these diseases, respectively. In the context of ASO treatment, the cytological characteristics and composition of cerebrospinal fluid (CSF) have recently garnered particular interest. This report presents a case series of CSF cytology findings in two patients with SMA and ALS revealing comparable unspecified macrophage inclusions following treatment initiation with nusinersen and tofersen. Yet, the presence of these "asophages" in the treatment course of two different ASOs is of unclear significance. While both treatments have been well tolerated, this phenomenon warrants attention, given the long-term nature of these treatments.

Background: Patients with Parkinson's disease (PD) have been reported to exhibit unusual bouts of creativity (e.g., painting, writing), in particular in the context of treatment with dopaminergic agents. Here we investigated divergent and convergent thinking thought to underlie creativity. In addition we assessed cognitive estimation.

Method: Twenty PD patients and 20 matched healthy control participants were subjected to the Guilford Alternate Uses task (divergent thinking), the remote associates task (convergent thinking) and two tests of cognitive estimation.

Results: No group differences were found for the convergent thinking task, while the Guilford Alternate Uses task revealed a decreased number of correct responses and a reduced originality for PD patients. Originality in PD was correlated to total daily dose of dopaminergic medication. Moreover, both tasks of cognitive estimation showed an impairment in PD.

Conclusion: Only minor effects were found for psychometric indices of subprocesses of creative thinking, while estimation, relying on executive functioning, is impaired in PD. We suggest to take a product oriented view of creativity in further research on altered creative processes in PD.

Background: While subthalamic nucleus deep brain stimulation (STN-DBS) improves the quality of life (QoL) of patients with Parkinson's disease (PD), the clinical parameters that predict this improvement remain debated. This retrospective study explored whether preoperative motor, cognitive, and affective parameters predict QoL or its components at 6 and 12 months after STN-DBS surgery.

Methods: QoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39) before (baseline), at 6 months (N = 90) and 12 months (N = 63) after STN-DBS surgery. Changes in the PDQ-39 and its subdomains were analysed with Wilcoxon signed-rank tests. In total, seven motor, cognitive, and affective parameters recorded at baseline were used in multiple linear regressions to predict QoL and its subdomains.

Results: QoL had improved significantly at six months post STN-DBS surgery. After 12 months, this effect remained significant but was less pronounced. At both time points, significant improvements in mobility, activities of daily living, stigma, and bodily discomfort were present. Correlation and linear regression analyses showed that preoperative QoL status and changes in QoL at 6 and 12 months after surgery were driven by preoperative dopaminergic medication, as well as motor (UPDRS-III medOFF and PIGD-subscore medOFF) and affective (HADS anxiety and depression) symptoms. In contrast, preoperative cognitive performance did not predict QoL at any time point.

Conclusion: Data show that preoperative motor and affective symptoms drive both QoL baseline status and changes in QoL after STN-DBS surgery. Thus, these clinical parameters need to be assessed appropriately to provide comprehensive presurgical advice to patients suffering from PD.

Background: Acquired brain injuries are among the most common causes of disability in adulthood. An intensive rehabilitation phase is crucial for recovery. However, there is a lack of concepts to further expand the therapeutic success after the standard rehabilitation period. Hereafter, the characteristics of a transsectoral, multiprofessional long-term neurorehabilitation concept and its effects on outcome at different ICF levels are described.

Methods: The P.A.N. Center for Post-Acute Neurorehabilitation combines living with 24/7 support of pedagogical staff with on-site outpatient therapy and medical care. A secondary data analysis was conducted on the records of all patients with completeted P.A.N. treatment between 01.01.2015 and 09.04.2022. Outcome parameters included demographic characteristics, diagnostics, Barthel Index (BI), the German scale "Hilfebedarf von Menschen mit Behinderung für den Lebensbereich Wohnen " (HMBW), the Canadian Occupational Performance Measure (COPM) and the destination after discharge. For BI and discharge destination, potential determinants of therapy success are evaluated.

Results: 168 patients were enrolled in the analyses. Significant improvements were observed in the BI (p < .001), with median values increasing from 55 to 80 points. The HMBW showed a significant decrease in the need for assistance in everyday living (p < .001), individual basic care (p < .001), shaping social relationship (p = .003) and communication (p < .001). Significant improvements were reported in the COPM total score for performance (p < .001) and satisfaction (p < .001). 72% of the patients were able to move in a community living arrangement with moderate need for support. Main predictive factor for discharge destination was the initial cognitive deficit. The comparison of the third-person scales BI and HMBW with the self-reported COPM showed that individually formulated patient goals are only insufficiently reflected in these global scales.

Discussion: The data show that a highly coordinated, trans-sectoral 24/7 approach of goal-oriented practice as pursued at P.A.N. is feasible and effective. We assume that the success of the intervention is due to the high intensity of therapies delivered over a long time and its interlink with real world practice. For a comprehensive analysis of rehabilitation success, it is necessary to record and evaluate individual patient goals, as these are not always reflected in the commonly used global scales.

Endovascular thrombectomy (EVT) is the most effective treatment for acute ischemic stroke caused by large vessel occlusion (LVO). Yet, long-term outcome (LTO) and health-related quality of life (HRQoL) in these patients have rarely been addressed, as opposed to modified Rankin scale (mRS) recordings. We analysed demographic data, treatment and neuroimaging parameters in 694 consecutive stroke patients in a maximum care hospital. In 138 of these patients with respect on receipt of written informed consent, LTO and HRQoL were collected over a period of 48 months after EVT using a standardised telephone survey (median 2.1 years after EVT). Age < 70 years (OR 4.82), lower NIHSS on admission (OR 1.11), NIHSS ≤ 10 after 24 h (OR 11.23) and complete recanalisation (mTICI3) (OR 7.79) were identified as independent predictors of favourable LTO. Occurrence of an infection requiring treatment within the first 72 h was recognised as a negative predictor for good long-term outcome (OR 0.22). Patients with mRS > 2 according to the telephone survey more often had complaints regarding mobility, self-care, and usual activity domains of the HRQoL. Our results underline a sustainable positive effect of effective EVT on the quality of life in LVO stroke. Additionally, predictive parameters of outcome were identified, that may support clinical decision making in LVO stroke.