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Identification of risk factors and prodromal markers for Parkinson’s disease (PD) and the understanding of the point in time of first occurrence is essential for the early detection of incident PD. In this three-center longitudinal, observational study, we evaluated the specific risk for PD associated with single or combinations of risk factors and prodromal markers. In addition, we evaluated which risk factors and prodromal markers emerge at which time before the diagnosis of PD. Of the 1,847 at-baseline PD-free individuals ≥50 years, 1,260 underwent the 5-year follow-up assessment. There were 21 cases of incident PD during the study period. Enlarged hyperechogenic substantia nigra was the most frequent baseline sign in individuals developing PD after 3 years (80.0 %) and 5 years (85.7 %) compared to healthy controls (17.5 %) followed by the occurrence of mild parkinsonian signs and hyposmia. Evaluation of the signs at the first follow-up assessment showed that individuals developing PD after two additional years showed the same pattern of signs as individuals who developed PD 3 years after baseline assessment.

There is evidence that nigrostriatal pathology may at least partly underlie mild Parkinsonian signs. We evaluated whether an increase in the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) could be predicted by the presence of risk and prodromal markers for neurodegenerative diseases in elderly individuals without those diseases. Therefore, we analyzed the UPDRS-III score and various risk and prodromal markers known to antecede neurodegenerative diseases in a population-based cohort comprising 807 individuals free of neurodegenerative diseases at baseline. After 5 years, eight persons (1.0 %) were diagnosed with Parkinson’s Disease (PD). Of those, seven (87.5 %) had motor worsening ≥3 points on the UPDRS-III from baseline to follow-up, one had two points increase. Of the 788 people without PD, 568 (72.1 %) showed no increase in the UPDRS-III scale, 220 (27.9 %) had ≥1 point increase and out of these 104 (13.2 %) had an increase of ≥3 points in the UPDRS-III score after 5 years. We identified an age >60 years (relative risk, RR = 1.7; confidence interval, CI 1.3–2.1) and the occurrence of ≥2 risk factors (RR = 1.5; CI 1.2-1.9) as possible predictors of motor progression. After 5 years, individuals with an increase in the UPDRS-III score had more often a one-sided reduced arm swing ( p  < 0.001) and identified less odors in the Sniffin’ sticks test ( p  < 0.041) than persons with stable motor performance. Our data support the assumption that progression of Parkinsonian signs assessed by the UPDRS-III parallels the development of prodromal markers for neurodegenerative diseases in the elderly population.

BackgroundThe spread of the novel coronavirus SARS-CoV-2 and the guidance from authorities for social distancing and media reporting lead to significant uncertainty in Germany. Concerns have been expressed regarding the underdiagnosing of harmful diseases. We explored the rates of emergency presentations for acute coronary syndrome (ACS) and acute cerebrovascular events (ACVE) before and after spread of SARS-CoV-2.MethodsWe analyzed all-cause visits at a tertiary university emergency department and admissions for ACS and ACVE before (calendar weeks 1–9, 2020) and after (calendar weeks 10–16, 2020) the first coronavirus disease (COVID-19) case in the region of the Saarland, Germany. The data were compared with the same period of the previous year.ResultsIn 2020 an average of 346 patients per week presented at the emergency department whereas in 2019 an average of 400 patients presented up to calendar week 16 (p = 0.018; whole year 2019 = 395 patients per week). After the first COVID-19 diagnosis in the region, emergency department visit volume decreased by 30% compared with the same period in 2019 (p = 0.0012). Admissions due to ACS decreased by 41% (p = 0.0023 for all; Δ − 71% (p = 0.007) for unstable angina, Δ − 25% (p = 0.42) for myocardial infarction with ST-elevation and Δ − 17% (p = 0.28) without ST-elevation) compared with the same period in 2019 and decreased from 142 patients in calendar weeks 1–9 to 62 patients in calendar weeks 10–16. ACVE decreased numerically by 20% [p = 0.25 for all; transient ischemic attack: Δ − 32% (p = 0.18), ischemic stroke: Δ − 23% (p = 0.48), intracerebral haemorrhage: Δ + 57% (p = 0.4)]. There was no significant change in ACVE per week (p = 0.7) comparing calendar weeks 1–9 (213 patients) and weeks 10–16 (147 patients). Testing of 3756 samples was performed to detect 58 SARS-CoV-2 positive patients (prevalence 1,54%, thereof one patient with myocardial and two with cerebral ischemia) up to calendar week 16 in 2020.ConclusionsThe COVID-19 pandemic was associated with a significant decrease in all-cause admission and admissions due to cardiovascular events in the emergency department. Regarding acute cerebrovascular events there was a numerical decrease but no significant difference.

Introduction To assess the value of optic nerve sheath diameter (ONSD) measurements at different time points to predict the malignant evolution in middle cerebral artery (MCA) infarction and to investigate the relationship between ONSD and infarct volume on follow-up computed tomography (CT). Methods In a single-center prospective observational study, we recruited patients with MCA infarction and age- and sex-matched controls. Clinical characteristics including NationaI Institutes of Health Stroke Scale (NIHSS) and ONSD measurement were assessed during the first five days after symptom onset. Volumetric analysis of the infarction was performed by a neuroradiologist, who was blinded to results of ONSD measurement and clinical examinations, based on  CT scans. Results We enrolled 29 patients with MCA infarction, including 10 with malignant MCA (mMCA) infarction and 14 controls. Mean ONSD on admission was already larger in patients who had developed an mMCA (5.99 ± 0.32 mm) compared to patients with MCA infarction (4.98 ± 0.53 mm; P  = 0.003), and to control patients (4.57 ± 0.29 mm; P  < 0.001). Correlation was observed between the ONSD mean value bilateral measures per individual and volumetric evaluation of cerebral infarction in the CT scan after one day (r = 0.623; P  = 0.002). An ONSD value of 5.6 mm predicted an mMCA with a sensitivity of 100% and specificity of 90% yielding a positive predictive value of 83% and negative predictive value of 100%. Conclusions ONSD measurement might be accurate for the noninvasive detection of increased ICP and for the recognition of patients being likely to develop mMCA.

Background and Purpose Endovascular treatment represents a well-established therapeutic option in patients with vertebral artery origin (VAO) stenosis. Our aim was to determine which factors affect short- and long-term restenosis rates after endovascular VAO therapy. Methods We conducted a single center analysis of 52 patients (36 men; age 64 ± 9.54 years) who underwent 55 endovascular procedures (27 balloon-assisted angioplasty [BAA], 28 stent-assisted angioplasty [SAA]) between 2005–2015. We collected data on patients clinical characteristics, medication and post-interventional follow-up visits. Results Overall, 15 of 55 vessels (27%) showed ≥70% restenosis at 1 year (short-term follow-up) and 18 after a mean follow-up of 52.9 ± 31.8 months (long-term). BMI ≥ 25 kg/m 2 was associated with ≥70% restenosis in short-term ( P  = 0.014) and long-term ( P  = 0.003) follow-up. Other risk factors, namely, hypertension, ischemic heart disease, smoking, diabetes mellitus, hypercholesterolemia, atrial fibrillation, CRP (>5 mg/l) or pre-treatment antiplatelet administration, statin intake and platelet count, were not associated with restenosis risk in the entire cohort or in patients in the BAA group (all P  > 0.05). BMI ( P  = 0.003) and ischemic heart disease ( P  = 0.041) were, in turn, associated with restenosis risk in the long-term follow-up in the SAA group. Patients undergoing BAA developed less frequently ( P  = 0.032) restenosis (18%) during long-term follow-up as compared to patients treated by stenting (46%). Conclusion BMI ≥ 25 kg/m 2 increases the odds for ≥70% restenosis of VAO while ischemic heart disease represents an additional risk factor in stented patients. Further studies are required to established therapeutic strategies lowering the restenosis rates in overweight individuals after VAO therapy, especially ones undergoing stenting.

Background: Decompressive hemicraniectomy (DHC) after space-occupying strokes among patients older than 60 years has been shown to reduce mortality rates but at the cost of severe disability. There is an ongoing debate about what could be considered an acceptable outcome for these patients. Data about retrospective consent to the procedure after lengthy time periods are lacking. Methods: This study included 79 consecutive patients who underwent DHC during a 7.75-year period. Surviving patients were assessed for functional and psychological outcome, quality of life (QoL) and retrospective consent for the procedure. Patients younger than 60 years were compared with older patients. Results: Of our 79 patients, 44 were younger than 60 years (median 50 years, interquartile range (IQR) 19-59 years) and 35 were older (median 68 years, interquartile range 60-87 years). The 30-day mortality rate was higher for the older group, but the difference was not statistically significant. Functional outcome was significantly better in the younger group: 31% of the patients in this group vs. 10% in the older group had a modified Rankin Scale score of 0-3 (p = 0.046). The mean National Institutes of Health Stroke Scale score was 17 ± 14 for the younger group and 29 ± 15 for the older group (p = 0.002). On the 36-Item Short Form Health Survey, with the exception of the item ‘General health', the older group reported higher values for all items, with statistically significant differences between the 2 groups on the items ‘Role limitation emotional' (p = 0.0007) and ‘Vitality' (p = 0.02). In the younger group, 29% of patients retrospectively declined consent for DHC opposed to 0% of patients in the older group (p = 0.07). Conclusions: Despite impaired functional outcome after DHC, indicators of QoL and retrospective consent are higher for patients older than 60 years over the long term. This finding should be taken into account by those who counsel patients and caregivers with regard to this serious procedure.

ObjectiveTranscranial sonography (TCS) shows characteristic hyperechogenicity of the substantia nigra (SN) in patients with Parkinson's disease (PD). Although this feature is well established, sufficient observer reliability and diagnostic accuracy are prerequisites for advancements of this method.MethodsThe authors investigated both aspects in a cross-sectional study with four blinded TCS raters in 22 PD patients and 10 healthy controls.ResultsAs expected, the authors found significant bilateral SN hyperechogenicity in PD patients. Quantitative computerised SN planimetry had a substantial intra- (intraclass correlation coefficient (ICC) 0.97 and 0.93 respectively for both hemispheres) and inter-rater reliability (ICC 0.84 and 0.89), while visual semiquantitative echogenicity grading of the SN revealed a moderate intrarater (weighted kappa 0.80 ipsilateral and 0.74 contralateral) and slight (0.33) to fair (0.51) inter-rater reliability only. Diagnostic accuracy measured as the area under the curve of receiver-operating characteristics plots was highest in TCS of the SN opposite the clinically most affected body side (planimetry 0.821, echogenicity grading 0.792) with a hyperechogenic area of 0.24 cm2 as the optimum cut-off value for the differentiation between PD and controls (sensitivity 79%, specificity 81%).ConclusionsThe data demonstrate that the observer variability of SN planimetry is low in the hands of experienced investigators. This approach also offers adequate diagnostic accuracy. The authors conclude that reliable SN TCS data on PD can be achieved in clinical routine and multicentre trials when standardised analysis protocols and certain quality criteria of brain parenchyma sonography are met.

Background and Purpose Endovascular treatment represents a well-established therapeutic option in patients with vertebral artery origin (VAO) stenosis. Our aim was to determine which factors affect short- and long-term restenosis rates after endovascular VAO therapy. Methods We conducted a single center analysis of 52 patients (36 men; age 64⯱ 9.54 years) who underwent 55 endovascular procedures (27 balloon-assisted angioplasty [BAA], 28 stent-assisted angioplasty [SAA]) between 2005-2015. We collected data on patients clinical characteristics, medication and post-interventional follow-up visits. Results Overall, 15 of 55 vessels (27%) showed [greater than or equal to]70% restenosis at 1 year (short-term follow-up) and 18 after a mean follow-up of 52.9⯱ 31.8 months (long-term). BMIâ¯[greater than or equal to] 25â¯kg/m.sup.2 was associated with [greater than or equal to]70% restenosis in short-term (Pâ¯= 0.014) and long-term (Pâ¯= 0.003) follow-up. Other risk factors, namely, hypertension, ischemic heart disease, smoking, diabetes mellitus, hypercholesterolemia, atrial fibrillation, CRP (>5â¯mg/l) or pre-treatment antiplatelet administration, statin intake and platelet count, were not associated with restenosis risk in the entire cohort or in patients in the BAA group (all Pâ¯> 0.05). BMI (Pâ¯= 0.003) and ischemic heart disease (Pâ¯= 0.041) were, in turn, associated with restenosis risk in the long-term follow-up in the SAA group. Patients undergoing BAA developed less frequently (Pâ¯= 0.032) restenosis (18%) during long-term follow-up as compared to patients treated by stenting (46%). Conclusion BMIâ¯[greater than or equal to] 25â¯kg/m.sup.2 increases the odds for [greater than or equal to]70% restenosis of VAO while ischemic heart disease represents an additional risk factor in stented patients. Further studies are required to established therapeutic strategies lowering the restenosis rates in overweight individuals after VAO therapy, especially ones undergoing stenting.

A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies.

Background: Enormous effort is being put into the identification and characterization of symptoms that may be used as predictive and progression markers in Parkinson's disease (PD). An impressive number of PD patients and individuals at risk for or in the prodromal stage of PD are currently followed in longitudinal studies; however, there does not exist an overview on the kind of markers evaluated and the assessments used. Methods: Information on the design, sample size, evaluated markers and assessments of 21 studies of the Joint Programme - Neurodegenerative Disease Research BioLoC-PD working group were collected by questionnaire. The studies were classified into at risk/prodromal or clinical PD cohorts. The assessments were grouped into quantitative assessments, investigator-rated assessments, investigator interviews, patient-rated questionnaires and caregiver-rated questionnaires. Results: Compilation of these data revealed an interesting consensus on evaluated markers, but there was an enormous variability of assessments. Furthermore, there is a remarkable similarity in the markers assessed and evaluation methods applied in the risk/prodromal and clinical PD cohorts. Conclusions: The inventory of the longitudinal cohorts that are part of the BioLoC-PD consortium reveals that there is a growing consensus on the markers that should be assessed in longitudinal cohort studies in PD. However, controversy still exists on the specific type of assessment. To allow comparison of data and common analyses it will be essential to harmonize scales and assessment outcomes.