CXCL13 as a biomarker in the diagnostics of European lyme Neuroborreliosis - A prospective multicentre study in Austria.

Background: 'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Objective: Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. Design and methods: This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. Results: We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant (P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Conclusion: Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

Short term cardiovascular symptoms improvement after deep brain stimulation in patients with Parkinson's disease: a systematic review.

BACKGROUND: Autonomic dysfunction is common and disabling in Parkinson's disease (PD). The effects of deep brain stimulation (DBS) on the cardiovascular system in PD remain poorly understood. We aimed to assess the effect of DBS on cardiovascular symptoms and objective measures in PD patients. METHODS: We conducted a systematic literature search in PubMed/MEDLINE. RESULTS: 36 out of 472 studies were included, mostly involving DBS of the subthalamic nucleus, and to a lesser extent the globus pallidus pars interna and pedunculopontine nucleus. Seventeen studies evaluated the effect of DBS on patient-reported or clinician-rated cardiovascular symptoms, showing an improvement in the first year after surgery but not with longer-term follow-up. DBS has no clear direct effects on blood pressure during an orthostatic challenge (n = 10 studies). DBS has inconsistent effects on heart rate variability (n = 10 studies). CONCLUSION: Current evidence on the impact of DBS on cardiovascular functions in PD is inconclusive. DBS may offer short-term improvement of cardiovascular symptoms in PD, particularly orthostatic hypotension, which may be attributed to dopaminergic medication reduction after surgery. There is insufficient evidence to draw conclusions on the direct effect of DBS on blood pressure and heart rate variability.

Dopamine increases risky choice while D2 blockade shortens decision time.

Dopamine is crucially involved in decision-making and overstimulation within dopaminergic pathways can lead to impulsive behaviour, including a desire to take risks and reduced deliberation before acting. These behavioural changes are side effects of treatment with dopaminergic drugs in Parkinson disease, but their likelihood of occurrence is difficult to predict and may be influenced by the individual's baseline endogenous dopamine state, and indeed correlate with sensation-seeking personality traits. We here collected data on a standard gambling task in healthy volunteers given either placebo, 2.5 mg of the dopamine antagonist haloperidol or 100/25 mg of the dopamine precursor levodopa in a within-subject design. We found an increase in risky choices on levodopa. Choices were, however, made faster on haloperidol with no effect of levodopa on deliberation time. Shortened deliberation times on haloperidol occurred in low sensation-seekers only, suggesting a correlation between sensation-seeking personality trait and baseline dopamine levels. We hypothesise that levodopa increases risk-taking behaviour via overstimulation at both D1 and D2 receptor level, while a single low dose of haloperidol, as previously reported (Frank and O'Reilly 2006), may block D2 receptors pre- and post-synaptically and may paradoxically lead to higher striatal dopamine acting on remaining striatal D1 receptors, causing speedier decision without influencing risk tolerance. These effects could also fit with a recently proposed computational model of the basal ganglia (Moeller and Bogacz 2019; Moeller et al. 2021). Furthermore, our data suggest that the actual dopaminergic drug effect may be dependent on the individual's baseline dopamine state, which may influence our therapeutic decision as clinicians in the future.

Disease-related patterns of in vivo pathology in Corticobasal syndrome.

PURPOSE: To assess disease-related patterns of in vivo pathology in 11 patients with Corticobasal Syndrome (CBS) compared to 20 healthy controls and 33 mild cognitive impairment (MCI) patients due to Alzheimer's disease. METHODS: We assessed tau aggregates with [18F]AV1451 PET, amyloid-ß depositions with [18F]AV45 PET, and volumetric microstructural changes with MRI. We validated for [18F]AV1451 standardised uptake value ratio (SUVRs) against input functions from arterial metabolites and found that SUVRs and arterial-derived distribution volume ratio (DVRs) provide equally robust measures of [18F]AV1451 binding. RESULTS: CBS patients showed increases in [18F]AV1451 SUVRs in parietal (P < 0.05) and frontal (P < 0.05) cortices in the affected hemisphere compared to healthy controls and in precentral (P = 0.008) and postcentral (P = 0.034) gyrus in the affected hemisphere compared to MCI patients. Our data were confirmed at the histopathological level in one CBS patient who underwent brain biopsy and showed sparse tau pathology in the parietal cortex co-localizing with increased [18F]AV1451 signal. Cortical and subcortical [18F]AV45 uptake was within normal levels in CBS patients. In parietal and frontal cortices of the most affected hemisphere we found also grey matter loss (P < 0.05), increased mean diffusivity (P < 0.05) and decreased fractional anisotropy (P < 0.05) in CBS patients compared to healthy controls and MCI patients. Grey matter loss and white matter changes in the precentral gyrus of CBS patients were associated with worse motor symptoms. CONCLUSIONS: Our findings demonstrate disease-related patterns of in vivo tau and microstructural pathology in the absence of amyloid-ß, which distinguish CBS from non-affected individuals and MCI patients.

"Atypical" atypical parkinsonism: Critical appraisal of a cohort.

BACKGROUND: Atypical parkinsonian conditions such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and Dementia with Lewy bodies (DLB) comprise 10-15% of parkinsonian syndromes. Misdiagnosis with Parkinson disease (PD) and within the entities is common, given the absence of reliable biomarkers. However a correct diagnosis is not only important in clinical practice, but also crucial for any trial attempting to identify biomarkers or new treatments. METHODS: Consecutive patients, who were referred to our tertiary center with a diagnosis of a particular AP were included and the medical records were reviewed retrospectively. We applied each set of current diagnostic research criteria to the respective cohort to see which features fit in and if there are any additional atypical features "outside" the classic definition. RESULTS: Sixty-nine patients were recruited between January 2013 and May 2015 clinically presenting with one of the following phenotypes: 14 MSA, 24 PSP, 19 CBS and 12 DLB. Up to 49% showed additional "atypical" features and approximately 10% eventually received an alternative diagnosis, in half of whom this being based on genetic testing. CONCLUSIONS: In a subset of our patients, despite the final diagnosis of an AP being maintained, there were additional "atypical" features. It remains to be seen if these reflect the clinical heterogeneity of APs, or should prompt a search for an alternative diagnosis. The search for biomarkers is more likely to be successful in homogenous groups of "typical" patients, hence the importance of recognizing "atypical" features.

Mental rotation and working memory in musicians' dystonia.

BACKGROUND: Mental rotation of body parts engages cortical-subcortical areas that are actually involved in the execution of a movement. Musicians' dystonia is a type of focal hand dystonia that is grouped together with writer's cramp under the rubric of "occupational dystonia", but it is unclear to which extent these two disorders share common pathophysiological mechanisms. Previous research has demonstrated patients with writer's cramp to have deficits in mental rotation of body parts. It is unknown whether patients with musicians' dystonia would display similar deficits, reinforcing the concept of shared pathophysiology. METHODS: Eight patients with musicians' dystonia and eight healthy musicians matched for age, gender and musical education, performed a number of tasks assessing mental rotation of body parts and objects as well as verbal and spatial working memories abilities. RESULTS: There were no differences between patients and healthy musicians as to accuracy and reaction times in any of the tasks. CONCLUSIONS: Patients with musicians' dystonia have intact abilities in mentally rotating body parts, suggesting that this disorder relies on a highly selective disruption of movement planning and execution that manifests only upon playing a specific instrument. We further demonstrated that mental rotation of body parts and objects engages, at least partially, different cognitive networks.