Propranolol Reduces Parkinson's Tremor and Inhibits Tremor-Related Activity in the Motor Cortex: A Placebo-Controlled Crossover Trial.

Objective: Parkinson's disease (PD) resting tremor is thought to be initiated in the basal ganglia and amplified in the cerebello-thalamo-cortical circuit. Because stress worsens tremor, the noradrenergic system may play a role in amplifying tremor. We tested if and how propranolol, a non-selective beta-adrenergic receptor antagonist, reduces PD tremor and whether or not this effect is specific to stressful conditions.

Identifying Individuals in the Prodromal Phase of Parkinson's Disease: A Prospective Cohort Study.

Objective: We prospectively evaluated how well combinations of signs and symptoms can identify individuals in the prodromal phase of Parkinson's disease (PD).

Methods: The study comprised 6,108 men who underwent repeated assessments of key prodromal features and were prospectively followed for the development of PD. Two composite measures of prodromal PD were evaluated: (i) the co-occurrence of constipation, probable rapid eye movement (REM) sleep behavior disorder (pRBD), and hyposmia, and (ii) the probability of prodromal PD based on the Movement Disorders Society (MDS) research criteria.

The Utility of Long-Read Sequencing in Diagnosing Early Onset Parkinson's Disease.

Objective: Variants in PRKN and PINK1 are the leading cause of early-onset autosomal recessive Parkinson's disease, yet many cases remain genetically unresolved. We previously identified a 7 megabases complex structural variant in a pair of monozygotic twins using Oxford Nanopore Technologies (ONT) long-read sequencing. This study aims to determine if ONT long-read sequencing can detect a second variant in other unresolved early-onset Parkinson's disease (EOPD) cases with 1 heterozygous PRKN or PINK1 variant.

Association that Neuroimaging and Clinical Measures Have with Change in Arm Impairment in a Phase 3 Stroke Recovery Trial.

Objective: Vagus nerve stimulation (VNS) paired with rehabilitation therapy improved motor status compared to rehabilitation alone in the phase III VNS-REHAB stroke trial, but treatment response was variable and not associated with any clinical measures acquired at baseline, such as age or side of paresis. We hypothesized that neuroimaging measures would be associated with treatment-related gains, examining performance of regional injury measures versus global brain health measures in parallel with clinical measures.

Methods: Baseline magnetic resonance imaging (MRI) scans in the VNS-REHAB trial were used to derive regional injury measures (extent of injury to corticospinal tract, the primary regional measure; plus extent of injury to precentral gyrus and postcentral gyrus; lesion volume; and lesion topography) and global brain health measures (degree of white matter hyperintensities, the primary global brain measure; plus volumes of cerebrospinal fluid, cortical gray matter, white matter, each thalamus, and total brain).

Atlas of Cerebrospinal Fluid Immune Cells Across Neurological Diseases.

Objective: Cerebrospinal fluid (CSF) provides unique insights into the brain and neurological diseases. However, the potential of CSF flow cytometry applied on a large scale remains unknown.

Methods: We used data-driven approaches to analyze paired CSF and blood flow cytometry measurements from 8,790 patients (discovery cohort) and CSF only data from 3,201 patients (validation cohort) collected across neurological diseases in a real-world setting.

Inhibition of Bone Morphogenetic Protein Signaling Prevents Tau Pathology in iPSC Derived Neurons and PS19 Mice.

Objective: Many neurodegenerative disorders share a common pathologic feature involving the deposition of abnormal tau protein in the brain (tauopathies). This suggests that there may be some shared pathophysiologic mechanism(s). The largest risk factor for the majority of these disorders is aging, suggesting involvement of the aging process in the shared pathophysiology.

Prophylactic Fetal Creatine Supplementation Improves Post-Asphyxial EEG Recovery and Reduces Seizures in Fetal Sheep: Implications for Hypoxic-Ischemic Encephalopathy.

Objective: Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal brain injury. Creatine is a dietary supplement that can increase intracellular phosphocreatine to improve the provision of intracellular adenosine triphosphate (ATP) to meet the increase in metabolic demand of oxygen deprivation. Here, we assessed prophylactic fetal creatine supplementation in reducing acute asphyxia-induced seizures, disordered electroencephalography (EEG) activity and cerebral inflammation and cell death histopathology.

Longitudinal Imaging Biomarkers Correlate with Progressive Motor Deficit in the Mouse Model of Charlevoix-Saguenay Ataxia.

Objective: In autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease, severity and age of onset vary greatly, hindering to objectively measure and predict clinical progression. Thickening of the retinal nerve fiber layer is distinctive of ARSACS patients, as assessed by optical coherence tomography, whereas conventional brain magnetic resonance imaging findings include both supratentorial and infratentorial changes. Because longitudinal imaging studies in ARSACS patients are not available to define these changes as biomarkers of disease progression, we aimed to address this issue in the ARSACS mouse model.

A Prospective Multicenter Analysis of Mobile Stroke Unit Cost-Effectiveness.

Objective: Given the high disease and cost burden of ischemic stroke, evaluating the clinical efficacy and cost-effectiveness of new approaches to prevent and treat ischemic stroke is critical. Effective ischemic stroke management depends on timely administration of thrombolytics after stroke onset. This study evaluates the cost-effectiveness associated with the use of mobile stroke units (MSUs) to expedite tissue plasminogen activator (tPA) administration, as compared with standard management through emergency medical services (EMS).

Towards a Unified Set of Diagnostic Criteria for Multiple Sclerosis.

Objective: The 2017 McDonald criteria continued the separation of diagnostic criteria for relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS) for historical, rather than biological, reasons. We aimed to explore the feasibility of a single, unified set of diagnostic criteria when applied to patients with suspected PPMS.

Methods: We retrospectively identified patients evaluated for suspected PPMS at 5 European centers.

Long-Term Follow Up in Anti-Contactin-1 Autoimmune Nodopathy.

Objective: To analyze long-term clinical and biomarker features of anti-contactin-1 (CNTN1) autoimmune nodopathy (AN).

Methods: Patients with anti-CNTN1 autoimmune nodopathy detected in our laboratory from which clinical information was available were included. Clinical features and treatment response were retrospectively collected.

Different Treatment Outcomes of Multiple Sclerosis Patients Receiving Ocrelizumab or Ofatumumab.

Objective: B-cell-depletion via CD20 antibodies is a safe and effective treatment for active relapsing multiple sclerosis (RMS). Both ocrelizumab (OCR) and ofatumumab (OFA) have demonstrated efficacy in randomized controlled trials and are approved for treatment of RMS, yet nothing is known on their comparative effectiveness, especially in the real-world setting.

Methods: This prospective cohort study includes patients that were started on either OCR or OFA between September 2021 and December 2023.

Neurologic Manifestations of Long COVID Disproportionately Affect Young and Middle-Age Adults.

Objective: To investigate neurologic manifestations of post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients across the adult lifespan.

Methods: Cross-sectional study of the first consecutive 200 PNP and 1,100 NNP patients evaluated at a Neuro-coronavirus disease 2019 (COVID-19) clinic between May 2020 and March 2023. Patients were divided into younger (18-44 years), middle-age (45-64 years), and older (65+ years) age groups.

Evaluation of Soluble Colony Stimulating Factor 1 Receptor (CSF1R) in Peripheral Blood as a Diagnostic Marker of CSF1R-Related Disorder (CSF1R-RD) in a Murine Model and CSF1R-RD Patients.

Mutations in colony stimulating factor 1 receptor (CSF1R) result in CSF1R-related disorder (CSF1R-RD). Our previous study demonstrated a proteolytic generation of a soluble CSF1R (sCSF1R) that could potentially serve as a diagnostic biomarker of CSF1R-RD. Herein, we observed that sCSF1R is released into peripheral serum as a highly glycosylated monomer in Csf1r mice that mimic the clinical symptoms of CSF1R-RD patients.

Oropouche Virus: An Emerging Neuroinvasive Arbovirus.

Oropouche virus (OROV) is an arthropod-borne virus (arbovirus) in the Orthobunyavirus genus and Peribunyaviridae viral family that is endemic to parts of South America, Central America, and the Caribbean. It has recently emerged in Cuba, and travel-imported cases are recently being reported in the United States and Europe. Typically maintained in a sylvatic cycle between certain forest sloths, non-human primates, birds, and mosquitoes, OROV disease outbreaks can occur in an urban cycle between certain biting midges and/or mosquitoes and humans.