BACKGROUND:Population-based data on mild parkinsonian signs (MPS) and parkinsonism in nonagenarians are scarce. OBJECTIVES:To estimate the prevalence of MPS, definite parkinsonism, and broader parkinsonian motor phenotypes; assess MPS after excluding idiopathic Parkinson disease and definite parkinsonism; and examine associations with sex and dementia in a cohort of nonagenarians. METHODS:This cross-sectional analysis included 144 participants from the Neurological Disorders in Central Spain (NEDICES) cohort aged ≥90 years on May 1, 1999; 97 were examined, and 47 had reliable indirect information. Unified Parkinson's Disease Rating Scale (UPDRS) motor data were evaluable in 96 of the examined participants. MPS were classified using established UPDRS-based operational criteria. Definite parkinsonism was defined primarily by a bradykinesia score ≥2 plus rigidity ≥1 or rest tremor ≥1; participants with an established Parkinson's disease diagnosis receiving antiparkinsonian treatment were also retained as definite cases when supported by prior clinical documentation. Bradykinesia ≥2 plus postural instability ≥2 in the absence of rest tremor and rigidity defined an instability-defined phenotype. Wilson's 95% confidence intervals (CIs) and two-sided Fisher's exact tests were used. RESULTS:MPS were present in 90/96 participants (93.8%; 95% CI, 87.0-97.1%). Prevalence remained 93.4% (85/91; 95% CI, 86.4-96.9%) after excluding idiopathic Parkinson's disease and 92.6% (75/81; 95% CI, 84.8-96.6%) after excluding all 15 examined definite cases. Definite parkinsonism affected 16/144 participants (11.1%; 95% CI, 7.0-17.3%), including 5 with idiopathic Parkinson's disease (3.5%; 95% CI, 1.5-7.9%). Among the 96 UPDRS-evaluable participants, 15 had definite parkinsonism, 7 additional participants had instability-defined parkinsonism, and inclusion of uncertain phenotypes expanded the broader parkinsonian motor spectrum to 63/96 (65.6%; 95% CI, 55.7%-74.4%). Dementia was more frequent with definite parkinsonism (13/16 vs 28/128; P < .001). Definite parkinsonism did not differ by sex; rest tremor was more frequent in men (P = .006). CONCLUSIONS:Parkinsonian motor features were frequent and phenotypically diverse among nonagenarians with evaluable UPDRS motor assessments. Definite parkinsonism represented only part of the broad parkinsonian motor spectrum, and idiopathic Parkinson's disease comprised only a small proportion of definite cases. These findings should not be interpreted either as synonymous with Parkinson's disease or as merely reflecting normal aging.
BACKGROUND:Lower urinary tract symptoms (LUTS) are among the most prevalent nonmotor complaints across the parkinsonian spectrum, yet they remain underutilized as diagnostic and management signals in neurology practice. Although prior reviews have characterized disease-specific patterns of urinary dysfunction, and recent guidelines address neurogenic LUTS broadly, no prior framework has explicitly focused on how the practicing neurologist can interpret LUTS as part of the diagnostic workup and integrate them into disease-specific management across parkinsonian disorders. METHODS:The aim of the review was to provide a neurology-centered narrative review reframing LUTS as diagnostic clues in parkinsonism and to propose a practical clinical evaluation framework for neurologists. We conducted a narrative review of published literature on LUTS across parkinsonian disorders, identified through PubMed/MEDLINE searches through March 2026, supplemented by manual review of reference lists and relevant guidelines. RESULTS:Disease-specific LUTS patterns can carry diagnostic relevance that can inform the neurologic differential diagnosis. Early urinary retention or elevated postvoid residual volume should raise suspicion for multiple system atrophy. Nocturia in Parkinson's disease is frequently multifactorial, requiring stepwise evaluation of dopaminergic timing, sleep disorders, nocturnal polyuria, and fluid shifts before bladder-directed therapy is initiated. LUTS may interact with mobility and falls through urgency-freezing convergence and nocturia-orthostatic hypotension overlap. Antimuscarinic agents carry compounded risks of cognitive impairment, delirium, and falls in this population. CONCLUSIONS:A pragmatic framework using symptom classification, postvoid residual measurement, red flag identification, and targeted pharmacologic guidance can support safe and timely LUTS management within routine neurology practice.
BACKGROUND:Interindividual variability in motor outcomes after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) remains incompletely understood. Glymphatic-related imaging abnormalities have been reported in PD, but their relevance to neuromodulation response is unclear. OBJECTIVES:To investigate whether preoperative glymphatic function, assessed using the Diffusion Tensor Imaging along the Perivascular Space (DTI-ALPS) index, is associated with motor outcomes after STN-DBS and whether hemispheric asymmetry provides additional explanatory value. METHODS:We retrospectively evaluated 74 advanced PD patients undergoing bilateral STN-DBS with ≥6 months follow-up. Preoperative assessment included 3 T MRI-derived ALPS measures, Fazekas score, perivascular space burden, MDS-UPDRS-III, levodopa responsiveness, and metabolic markers. Primary outcome was percentage motor improvement at follow-up. Multivariable regression models assessed ALPS associations after adjustment for levodopa responsiveness and measured clinical covariates. RESULTS:Lower ALPS asymmetry index (AI) was independently associated with greater percentage motor improvement (standardized β = -0.508, p < 0.001), while greater preoperative levodopa responsiveness was also associated with improvement (β = 0.740, p < 0.001). Lower ALPS-AI was additionally associated with axial motor improvement and responder status at both ≥50% and ≥ 33% thresholds. All four principal levodopa-adjusted ALPS-AI associations remained significant after Benjamini-Hochberg correction (all pFDR≤0.0069). Mean ALPS index, Fazekas score, and perivascular space burden were not associated with motor outcomes. CONCLUSIONS:Preoperative glymphatic asymmetry was associated with motor outcomes after STN-DBS independently of levodopa responsiveness and measured clinical covariates. ALPS-derived asymmetry may capture outcome variability not reflected by conventional imaging, although prospective validation and evaluation alongside lead localization, stimulation parameters, and programming factors are required.
BACKGROUND:REM sleep behavior disorder (RBD) is now increasingly recognized in progressive supranuclear palsy (PSP), with unclear clinical relevance. OBJECTIVES:To determine the frequency of pRBD and non-motor symptoms in PSP and association between the two. METHODS:We enrolled 150 consecutive patients with PSP and 150 age- and sex-matched controls. Probable RBD (pRBD) was identified using the REM Sleep Behavior Disorder Screening Questionnaire. Clinical, cognitive, and NMS scores were measured using validated rating scales. Group comparisons and regression analyses were performed. RESULTS:The mean age at study was 69.1 ± 7.5 years, pRBD was identified in 18.7% of patients with PSP and in none of the controls. Patients with pRBD had a greater NMS burden (p < 0.001) and poorer quality of life (p = 0.041). Attention/memory (β = 0.196, p = 0.015) and gastrointestinal symptoms (β = 0.255, p = 0.003) independently predicted pRBD. CONCLUSIONS:pRBD is a common non-motor feature of PSP and is associated with greater non-motor symptom burden and poorer quality of life.
BACKGROUND:DYT-PRKRA (formerly DYT16) is an autosomal recessive dystonia-parkinsonism syndrome caused by biallelic pathogenic variants in PRKRA, a gene encoding the stress-responsive protein PACT. While early-onset generalized dystonia and speech disturbance are well-recognized features, pathological startle has not previously been described. CASES:We report two siblings with genetically confirmed DYT-PRKRA (homozygous pathogenic PRKRA variant p.Pro222Leu). Case 1, a 37-year-old male, presented with childhood-onset dystonia and persistent pathological startle. Case 2, a 33-year-old female, showed milder dystonia but disabling startle episodes with psychosocial impact. Neurophysiology revealed non-habituating pathological startle responses, with short-latency EMG bursts across proximal and distal muscles consistent with brainstem hyperexcitability. LITERATURE REVIEW:Startle responses are classically associated with hyperekplexia but may occur in other movement disorders. Reflex hyperexcitability is seen in dystonia, yet overt startle is rarely reported. In DYT-SGCE and idiopathic dystonias, brainstem hyperexcitability is recognized, but PRKRA directly modulates PKR within the integrated stress response, suggesting a unique vulnerability in stress-sensitive reflex circuits. CONCLUSIONS:These cases expand the clinical phenotype of DYT-PRKRA to include pathological startle, a feature not previously reported in PRKRA-related disease and highlight the importance of neurophysiological evaluation in phenotyping genetically confirmed dystonias.
BACKGROUND:Anti-amphiphysin stiff-person spectrum disorders (SPSD) are paraneoplastic syndromes with few Asian reports and limited clinico-demographic data. We present two Asian cases alongside the largest pooled cohort analysis to date (n = 64). CASES:Two breast adenocarcinoma-associated cases are presented. Case 1 (Chinese Malaysian) describes an unusual upper-limb stiff-limb syndrome (SLS) resolving fully following early tumor resection and intravenous immunoglobulin (IVIG). Case 2 (India) describes stiff-person syndrome (SPS) with relief from IVIG, but died from cancer progression. LITERATURE REVIEW:Analysis of 64 cases of anti-amphiphysin SPSD revealed a stiffness hierarchy: lower limbs (37/45 = 82.2%) were most frequently affected, followed by upper limbs (57.8%), paraspinal muscles (55.6%), neck (28.9%), abdomen (26.7%), thorax (8.9%), and face (2.2%). Malignancy occurred in 93.8% (n = 60/64), the majority involving breast (73.4%, n = 47/64) or lung (14.1%, n = 9/64). SPSD symptoms preceded cancer detection in 80.0% (n = 32/40) by a median of 8 (range:1-60) months. Overall, the majority of cases (25/44 = 56.8%) had good functional outcomes (modified Rankin Scale ≤2). Good outcomes were documented in most (19/29 = 65.5%) patients receiving "triple" (symptomatic, immunomodulatory, oncological) therapy and those with oncological remission reported (10/13 = 76.9%). CONCLUSIONS:Properly managed, anti-amphiphysin SPSD has good outcomes in the majority of patients, particularly when the underlying cancer is successfully treated. Atypical presentations, including upper-limb SLS, warrant high diagnostic suspicion.
BACKGROUND:Impulse control-related behavioral disorders refer to a group of compulsive behaviors seen in patients with Parkinson's disease (PD), comprising impulse control disorders (ICD), dopamine dysregulation syndrome (DDS), and punding. Over the years, numerous studies have been published on their prevalence, risk factors, neuroimaging, genetics, and management. More evidence now suggests that each disorder involves a distinct neurobiological mechanism. Although our understanding has improved, early recognition and appropriate treatment remain a significant challenge for clinicians, patients, and caregivers alike. OBJECTIVE:We aimed to summarize the definitions, underlying neurobiological mechanisms, validated assessment tools (for screening and rating), management strategies, and future directions for each of these impulse-control and related behavioral disorders (ICBD). METHODS:We performed a scoping review of PubMed, Embase, and psycINFO. RESULTS:A database search identified 540 articles, of which 110 were selected for full-text review. We classified the articles into 6 themes as follows: prevalence, risk factors, genetics, behavioral studies, neuroimaging, and treatment options. Based on the selected articles, we discussed the clinical phenotypes, pathophysiology, and treatment approaches for ICD, DDS, and punding. Identified knowledge gaps include the limited understanding of the pathophysiology of punding and validated rating scales for clinical use in assessing punding and DDS. Future research directions include investigating the role of selective serotonin 5-hydroxytryptamine 2A receptor inverse agonists, selective D1/D5 partial dopamine agonists, and transcranial magnetic stimulation in the treatment of ICBDs in PD. CONCLUSION:Early recognition and distinguishing among the different ICBDs are essential to enable early intervention, specific tailored management, and monitoring of these disorders and their respective treatment effects.
BACKGROUND:Levodopa remains the most effective pharmacological treatment for Parkinson's disease (PD), but long-term use commonly leads to motor complications such as levodopa-induced dyskinesia (LID) and motor fluctuations, significantly contributing to disability. Exercise is well-established for improving motor and non-motor symptoms in PD; however, its effect on motor complications remains unclear. OBJECTIVE:To determine whether exercise reduces motor complications in people with PD. METHODS:Systematic searches were conducted in five databases. Eligible randomized controlled trials assessed motor complications pre- and post- exercise intervention using the Unified Parkinson's Disease Rating Scale IV (UPDRS IV) or its modified version were included. Methodological quality was assessed using the Physiotherapy Evidence Database scale. Studies rated as good quality and reporting sufficient outcome data were included in a random-effects meta-analysis. Meta-regression analyses explored potential moderating effects of medication status (on/off) and control group type (active/passive). RESULTS:Twenty-three studies were included; 14 were rated as good quality, of which 11 provided sufficient data for meta-analysis. Sample sizes ranged from 11 to 125 participants, and interventions varied in type, intensity and duration. Meta-analysis showed no significant effect of exercise on motor complications. Meta-regression analyses showed no moderating effect of medication status or control group type. CONCLUSIONS:Current evidence does not support an effect of exercise on LID or motor fluctuations in PD. These findings should be interpreted with caution, given the low baseline severity of motor complications (UPDRS IV 3.47), small sample sizes, heterogeneity of interventions, and the absence of trials specifically designed to target motor complications.
