Longitudinal Changes in Patient- and Clinical-Reported Outcomes in Early Spinocerebellar Ataxia Types 1, 2, 3, and 6 from the IDEA Study.

Background: Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia-specific, sensitive to change, clinically relevant, and meaningful to patients.

Objectives: To evaluate the longitudinal 1- and 2-year performances of different patient reported outcomes, including the Patient Reported Outcome Measure of Ataxia (PROM-Ataxia), and clinician reported outcomes, including FARS and SARA, in those with early manifest symptoms of SCA 1, 2, 3, and 6.

Methods: We studied 53 patients with early stage SCA1-3 and SCA6 from The Instrumented Data Exchange for Ataxia Study and 24 age-matched healthy controls.

A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor.

Background: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABA receptors.

Objective: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET).

Methods: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days.

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability.

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

Background: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor.

Methods: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months.

Parallel PARKing: Parkinson's genes function in common pathway.

Parkinson's disease (PD) is associated with diverse genetic and environmental susceptibilities. Functional connections between PD genes have remained elusive. In this issue of Neuron, MacLeod et al.

The curious case of phenocopies in families with genetic Parkinson's disease.

Monogenic forms of Parkinson's disease account for ∼3% of all "idiopathic" Parkinson's disease. With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.

Serotonin and Parkinson's disease: On movement, mood, and madness.

An appreciation of the multiple roles that serotonin (5-HT) may play in Parkinson's disease (PD) has increased in recent years. Early pathological studies in PD demonstrated nonselective reductions of 5-HT in brain tissue but little correlation to comorbidities such as dyskinesia and mood disturbance. This, combined with treatment failures using serotonergic drugs in comparison to levodopa, meant the field was largely neglected until recently.

Parkinson's disease--opportunities for novel therapeutics to reduce the problems of levodopa therapy.

Long-term treatment for Parkinson's disease (PD) with the dopamine-precursor levodopa (l-DOPA) results in the development of motor fluctuations, including involuntary movements, termed l-DOPA-induced dyskinesia (LID). Currently, effective treatments for LID are limited. The neurodegenerative processes underlying PD result in loss of serotonin (5-HT) input from the dorsal raphe nucleus (DRN) to the striatum, but to a lesser extent than loss of dopamine input.