Objective We aimed to estimate the incidence of cerebral sinus and venous thrombosis (CVT) within 1 month from first dose administration and the frequency of vaccine‐induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA‐1273, in Germany. Methods A web‐based questionnaire was e‐mailed to all departments of neurology. We requested a report of cases of CVT occurring within 1 month of a COVID‐19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of 9 German states. Results A total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were younger than 60 years. Fifty‐three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%) vaccination, and none after mRNA‐1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within 1 month from first dose administration was 0.55 (95% confidence interval [CI] = 0.38–0.78) per 100,000 person‐months (which corresponds to a risk of CVT within the first 31 days of 0.55 per 100,000 individuals) for all vaccines and 1.52 (95% CI = 1.00–2.21) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (95% CI = 3.46–34.98) for ChAdOx1 compared to mRNA‐based vaccines and 3.14 (95% CI = 1.22–10.65) for females compared to non‐females. In 26 of 45 patients with CVT (57.8%), VITT was graded highly probable. Interpretation Given an incidence of 0.02 to 0.15 per 100,000 person‐months for CVT in the general population, these findings point toward a higher risk for CVT after ChAdOx1 vaccination, especially for women. ANN NEUROL 2021

BackgroundParkinson’s disease (PD) is the second most frequent neurodegenerative disease of the elderly. Patients suffer from various motor and non-motor symptoms leading to reduced health-related quality of life (HRQOL) and an increased mortality. Their loss of autonomy due to dementia, psychosis, depression, motor impairments, falls, and swallowing deficits defines a phase when palliative care interventions might help to sustain or even improve quality of life.ObjectiveThe aim of this study was to investigate the current status of palliative care implementation and quality of life in a local cohort of advanced PD patients in order to frame and improve future care.Methods76 geriatric patients with advanced idiopathic PD meeting the inclusion criteria for palliative care interventions were clinically evaluated by neurological examination using Movement Disorders Society Unified Parkinson’s Disease Rating Scale, Barthel Index, Montreal Cognitive Assessment Test, and a structured interview concerning palliative care implementation.ResultsHRQOL is severely reduced in our cohort of geriatric advanced PD patients. We found motor deficits, impairment of activities of daily living, depression, and cognitive decline as most relevant factors determining decreased HRQOL. Only 2.6% of our patients reported present implementation of palliative care. By contrast, 72% of the patients indicated an unmet need for palliative care.ConclusionQuality of life is dramatically affected in advanced PD patients. However, we found palliative care to be implemented extremely rare in their treatment concept. Therefore, geriatric patients suffering from advanced PD should be enrolled for palliative care to provide adequate and holistic treatment which may improve or sustain their quality of life.

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Several complementary mass spectrometric imaging techniques allow mapping of various analytes within biological tissue sections. Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) quantitatively detects elements and isotopes with very high sensitivity and a particularly high dynamical range. Matrix-assisted laser desorption/ionization ion mobility mass spectrometry (MALDI-IM-MS) allows a pixel-by-pixel classification and identification of biomolecules.In order to dispose of the healthy hemisphere as an internal calibrant in addition to routinely used external standards, adjacent brain sections of mice with a unilateral 6-OHDA lesion of the medial forebrain bundle were chosen as exemplary samples. We demonstrate a comprehensive way of data acquisition and analysis by coregistering mass spectrometric data on photomicrographs as common reference space and thus providing trimodal spatial information. Registering subsequent planar element maps yielded continuous 3-dimensional data sets. Furthermore, we introduce a correction of MSI data for variable slice thickness applicable to all MSI techniques. In the present case, we observed increased concentrations of iron, manganese, and copper in the lesioned substantia nigra while monounsaturated lipid levels were decreased in the identical region of interest. Our techniques provide new insights into the intricate spatial relationship of morphology and chemistry within tissue.

Background:Advanced Parkinson’s disease (PD) may place a high burden on patients and their caregivers. Understanding the determinants of caregiver burden is of critical importance. This understanding requires the availability of adequate assessment tools. Recently, the Parkinson’s disease caregiver burden questionnaire (PDCB) has been developed as a PD-specific measure of caregiver burden. However, the PDCB has only been evaluated in a sample of Australian caregivers of patients at a less advanced stage of the disease.Objective:We tested whether a German translation of the PDCB qualifies as an adequate measure of caregiver burden in a German sample of caregivers of advanced patients with PD.Methods:We collected PDCB data from 65 caregivers of advanced patients with PD. Reliability of the scale was assessed and compared against the original version. To validate the German version of the PDCB, we examined the correlations with the caregiver burden inventory (CBI), the short form 36 health survey (SF-36), the Parkinson’s disease quality of life questionnaire 39 (PDQ-39), disease duration, and the amount of caregiving time.Results:The total PDCB score proved to be reliable and to be significantly related to CBI and SF-36 scores. PDCB scores also increased with increasing amounts of caregiving time.Conclusions:The German version of the PDCB appears to be an adequate measure of caregiver burden in caregivers of advanced PD patients.

Parkinson’s disease (PD) is a slowly progressive neurodegenerative movement disorder that leads to impairments in activities of daily living. In addition to reducing patients’ quality of life, this disease also affects caregivers’ well-being. Until recently, caregiver burden was mainly assessed by generic questionnaires, which do not take the characteristics of the chronic disease into consideration. In the case of PD, this issue has been addressed by the introduction of the “Parkinson’s disease caregiver burden” questionnaire (PDCB). Data on longitudinal trajectories of caregiver burden are still missing in the literature. In this study, we assessed the one-year trajectory of caregiver burden by the PDCB as a disease-specific questionnaire. Further, gender-specific aspects of caregiver burden were analyzed by applying a caregiver task questionnaire. PDCB total score (n = 84 patients and caregivers) did not significantly change from baseline (30.4) to one year at follow-up (31.5). No significant difference was detected between female and male caregivers in global burden and-specific caregiver tasks. Our data showed only a mild increase of caregiver burden in the timeframe of one year. Gender-specific differences do not seem to impact-specific caregiver tasks in the presented study population.

Objective: To estimate alterations in neurometabolic profile of patients with early stage Parkinson's disease (PD) by using a short echo-time whole brain magnetic resonance spectroscopic imaging (wbMRSI) as possible biomarker for early diagnosis and monitoring of PD. Methods: 20 PD patients in early stage (H&Y ≤ 2) without evidence of severe other diseases and 20 age and sex matched healthy controls underwent wbMRSI. In each subject brain regional concentrations of metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), glutamine (Gln), glutamate (Glu), and myo-inositol (mIns) were obtained in atlas-defined lobar structures including subcortical basal ganglia structures (the left and right frontal lobes, temporal lobes, parietal lobes, occipital lobes, and the cerebellum) and compared between patients and matched healthy controls. Clinical characteristics of the PD patients were correlated with spectroscopic findings. Results: In comparison to controls the PD patients revealed altered lobar metabolite levels in all brain lobes contralateral to dominantly affected body side, i.e., decreases of temporal NAA, Cho, and tCr, parietal NAA and tCr, and frontal as well as occipital NAA. The frontal NAA correlated negatively with the MDS-UPDRS II ( R = 22120.585, p = 0.008), MDS-UPDRS IV ( R = −0.458, p = 0.048) and total MDS-UPDRS scores ( R = −0.679, p = 0.001). Conclusion: In early PD stages metabolic alterations are evident in all contralateral brain lobes demonstrating that the neurodegenerative process affects not only local areas by dopaminergic denervation, but also the functional network within different brain regions. The wbMRSI-detectable brain metabolic alterations reveal the potential to serve as biomarkers for early PD.

Parkinson’s disease (PD) is a chronic progressive movement disorder with severe reduction in patients’ health-related quality of life (HR-QoL). Motor and cognitive symptoms are especially linked with decreased PD patients’ HR-QoL. However, the relationship of these symptoms to caregiver burden is relatively unclear. Influence of the Montreal Cognitive Assessment scale (MoCA) as a cognitive screening tool and Movement Disorders Society Unified Parkinson’s disease Rating Scale MDS-UPDRS symptoms in relation to patients’ HR-QoL and caregivers` burden was analyzed. PD patients (n = 124) completed MDS-UPDRS, MoCA, and the PD questionnaire 8 (PDQ-8) as a measure of quality of life. Caregivers (n = 78) were assessed by the PD caregiver burden inventory (PDCB). PDQ-8 and PDCB scores were regressed on MDS-UPDRS subscales and MoCA subscores. PDQ-8 correlated with attention (R2 0.1282; p<0.001) and executive (R2 0.0882; p 0.001) MoCA subscores and all parts of the MDS-UPDRS. PDCB correlated most strongly with MDS-UPDRS part III motor symptoms (R2 0.2070; p<0.001) and the MoCA attention subscore (R2 0.1815; p<0.001). While all facets of PD symptoms assessed by the MDS-UPDRS relate to PD patients’ quality of life, motor symptoms are the most relevant factor for the prediction of caregiver burden. In addition, patients’ attentional symptoms seem to affect not only them, but also their caregivers. These findings show the potential of a detailed analysis of MDS-UPDRS and MoCA performance in PD patients.