Bradykinesia in dystonic hand tremor: kinematic analysis and clinical rating.

Introduction: Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either "pure" dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT). Methods: The protocol consisted of two main parts. Initially, the kinematic recording of repetitive FT was performed using optical hand tracking system (Leap Motion Controller). The values of amplitude, amplitude decrement, frequency, frequency decrement, speed, acceleration and number of halts of FT were calculated. Subsequently, three independent movement disorder specialists from different movement disorders centres, blinded to the diagnosis, rated the presence of FT bradykinesia based on video recordings. Results: Thirty-six subjects participated in the study (12 DT, 12 HC and 12 early-stage PD). Kinematic analysis revealed no significant difference in the selected parameters of FT bradykinesia between DT patients and HC. In comparisons between DT and PD patients, PD patients exhibited bigger amplitude decrement and slower FT performance. In the blinded clinical assessment, bradykinesia was rated, on average, as being present in 41.6% of DT patients, 27.7% of HC, and 91.7% of PD patients. While overall inter-rater agreement was moderate, weak agreement was noted within the DT group. Discussion: Clinical ratings indicated signs of bradykinesia in almost half of DT patients. The objective kinematic analysis confirmed comparable parameters between DT and HC individuals, with more pronounced abnormalities in PD across various kinematic parameters. Interpretation of bradykinesia signs in tremor patients with DT should be approached cautiously and objective motion analysis might complement the diagnostic process and serve as a decision support system in the choice of clinical entities.

Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults.

Objective: Strong evidence supports the benefits of exercise for healthy ageing, including reduced risk of neurodegenerative diseases. Recent studies suggested interorgan crosstalk as a key element of systemic adaptive response, however, the role of specific molecules in mediating exercise effects on the human brain are not fully understood. In the present study, we explored the exercise-related regulation of Growth Differentiation Factor 11 (GDF11) in cerebrospinal fluid (CSF) and blood. Methods: The samples of serum, plasma and CSF were obtained before and 60min after acute exercise (90min run) from twenty healthy young individuals. Additional serum and plasma samples were collected immediately after run. GDF11 protein content (immunoblotting), body composition (bioelectrical impedance), physical fitness (VO2max, cycle spiroergometry) and cognitive functions (standardized computerized tests, Cogstate) were evaluated. Results: Running decreased GDF11 protein content in CSF (-20.6%. p=0.046), while GDF11 in plasma and serum were not regulated. Two GDF11-specific antibodies of different origin were used to corroborate this result. Individuals with higher physical fitness displayed greater exercise-induced decrease of GDF11 in CSF than those with lower physical fitness (p=0.025). VO2max correlated positively with GDF11 in serum (r=0.63, p=0.020) as well as with the exercise-induced change in GDF11 levels in CSF (r=0.59, p=0.042). Indirect measure of blood-brain barrier permeability (i.e. CSF/serum albumin ratio) tended to positively correlate with CSF/serum GDF11 ratio (p=0.060). CSF levels of GDF11 correlated positively with cognitive functions, including working memory, both before and after run (p<0.05). Conclusion: Running-induced down-regulation of the GDF11 protein in the cerebrospinal fluid of healthy young individuals indicates the potential role of GDF11 in the exercise-induced cross-talk between periphery and the brain.

Tolcapone improves outcomes in patients with Parkinson disease treated by levodopa/carbidopa intestinal gel: A pilot study.

BACKGROUND: Patients with Parkinson disease (PD) treated with levodopa/carbidopa intestinal gel (LCIG) have higher prevalence of hyperhomocysteinemia and peripheral nerves damage. OBJECTIVE: The aim of our study was to test the effect of catechol-O-methyl transferase inhibitor tolcapone-as an add-on therapy to LCIG in patients with PD-on homocysteine (HCY) metabolism and nerve conduction study (NCS) parameters. METHODS: We evaluated NCS and serum B12, folic acid, and homocysteine in 16 patients with advanced PD on LCIG. Quality of life (QoL) was also assessed. Six subjects were treated with tolcapone add-on therapy (and LCIG dose reduction), 5 with B vitamin supplementation, and 5 without additional treatment. RESULTS: The level of HCY increased among patients without treatment (4.95 ± 12.54), and decreased in the vitamin (-17.73 ± 11.82) and tolcapone groups (-8.81 ± 8.36). Patients with tolcapone demonstrated improvement in polyneuropathic symptoms and signs compared with patients treated with vitamins or those without additional treatment (-0.83, d = 0.961). Although the most robust improvement in NCS parameters were observed with tolcapone, the findings were inconsistent to prove the effect of any intervention. Only tolcapone treatment was associated with improvement in QoL (d = 1.089). CONCLUSION: Our study indicates potential of tolcapone add-on therapy in LCIG treated patients in control of homocysteine levels, and improvement of polyneuropathic symptoms, as well as QoL.

Cerebrospinal fluid and plasma metabolomics of acute endurance exercise.

Metabolomics has emerged as a powerful new tool in precision medicine. No studies have yet been published on the metabolomic changes in cerebrospinal fluid (CSF) produced by acute endurance exercise. CSF and plasma were collected from 19 young active adults (13 males and 6 females) before and 60 min after a 90-min monitored outdoor run. The median age, BMI, and VO2 max of subjects was 25 years (IQR 22-31), 23.2 kg/m2 (IQR 21.7-24.5), and 47 ml/kg/min (IQR 38-51), respectively. Targeted, broad-spectrum metabolomics was performed by liquid chromatography, tandem mass spectrometry (LC-MS/MS). In the CSF, purines and pyrimidines accounted for 32% of the metabolic impact after acute endurance exercise. Branch chain amino acids, amino acid neurotransmitters, fatty acid oxidation, phospholipids, and Krebs cycle metabolites traceable to mitochondrial function accounted for another 52% of the changes. A narrow but important channel of metabolic communication was identified between the brain and body by correlation network analysis. By comparing these results to previous work in experimental animal models, we found that over 80% of the changes in the CSF correlated with a cascade of mitochondrial and metabolic changes produced by ATP signaling. ATP is released as a co-neurotransmitter and neuromodulator at every synapse studied to date. By regulating brain mitochondrial function, ATP release was identified as an early step in the kinetic cascade of layered benefits produced by endurance exercise.