Movement disorders occur in early-onset hereditary spastic paraplegia (HSP), but their prevalence, genotype associations, and clinical impact are not well defined. To delineate the spectrum and frequency of movement disorders across childhood-onset HSP genotypes and assess associations with clinician- and caregiver-reported outcomes. We performed a cross-sectional analysis of 428 children and young adults with molecularly confirmed HSP enrolled in a multicenter natural history study. Standardized clinical phenotyping and video examinations were reviewed. Movement and motor disorders (dystonia, ataxia, parkinsonism, tremor, choreoathetosis) were identified using predefined criteria. Associations with SPATAX-EUROSPA disability stage (SPATAX), Spastic Paraplegia Rating Scale (SPRS; total and spasticity subscore), Modified Ashworth Scale, and Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) quality-of-life scores were analyzed with nonparametric tests and multivariable linear models adjusted for age and sex. Movement disorders were present in 27.6% (118/428) of participants; 22.8% of these had ≥2 movement disorders. Dystonia (16.4%) and ataxia (10.0%) predominated. Distinct genotype-specific patterns were observed: dystonia in SPG4, SPG3A, and AP-4-HSP; parkinsonism in SPG11; and ataxia in SPG15, SPG76, SPG7, SPG5a, and SPG46. Presence of any movement disorder correlated with greater disability and motor burden and lower quality of life. In adjusted models, dystonia and parkinsonism were associated with higher SPATAX and SPRS scores, whereas ataxia and tremor correlated with lower scores; dystonia showed the largest decrement in CPCHILD. Movement disorders are common, genotype-specific, and clinically impactful features of childhood-onset HSP. Routine screening and genotype-tailored management of movement disorders, especially dystonia, may improve functional outcomes and quality of life. © 2025 International Parkinson and Movement Disorder Society.

Movement disorders, especially hyperkinetic movement disorders, can present in emergency services in an acute and/or severe form and are aetiologically heterogeneous. Because limited data exist on the epidemiology and clinical presentation of hyperkinetic movement disorders in China, a retrospective study was performed to investigate the spectrum of various hyperkinetic movement disorder emergencies and their underlying causes. To reveal the spectrum of hyperkinetic movement disorder emergencies from a retrospective study and investigate their underlying causes to aid in their management. In total, 74 adults presenting with hyperkinetic movement disorders were recruited between January 2023 and September 2024, and data related to clinical information, cranial CT/MRI scans, and blood tests and other necessary examinations were collected. The frequency of hyperkinetic movement disorder emergencies accounted for 0.125% (74/59 354) of the total patients in the emergency room during this period. The most common type of hyperkinetic movement disorder emergency was myoclonus (44.6%), followed by tremors (37.8%), dystonia (16.2%) and chorea (1.4%). The time delay to medical consultation was divided into three phases: ≤ 24 h (67.6%), 24 h-28 days (23.0%), and > 28 days (9.5%). In addition to the undetermined aetiological factors (31.1%), six aetiological groups were recognised: metabolic disease (16.2%), infection and inflammation (16.2%), psychogenesis (9.5%), drug-induced disorders (9.5%), neurodegenerative diseases (9.5%), and stroke (8.1%). During the 2-year follow-up period, the morbidity rate in our study was 5.4% (4/74). This study provides a landscape of adult patients presenting to neurology emergency services with hyperkinetic movement disorders in China.

DYT-PRKRA is a rare, autosomal recessive movement disorder caused by mutations in the PRKRA gene. While PRKRA mutations are recognized in DYT-PRKRA, a significant number of identified variants are still classified as "variant of uncertain significance" (VUS). In this study we identified a causative variant previously reported as a VUS. A 4.5-year-old female born to consanguineous, healthy parents presented with progressive neurodevelopmental regression, similar to two affected relatives. Whole-exome sequencing was performed, and segregation analysis was conducted across two generations. A homozygous PRKRA c.74A>G (p.Lys25Arg) variant co-segregated with the DYT-PRKRA phenotype. Unaffected family members were identified as heterozygous carriers. This is the first report of DYT-PRKRA in the Iranian population. Strong evidence from familial segregation and in silico analyses support the reclassification of this variant to likely pathogenic. This reclassification has significant implications for the diagnosis and genetic counseling of families affected by DYT-PRKRA. © 2025 International Parkinson and Movement Disorder Society.

Tuberculosis (TB) of the central nervous system (CNS) is a severe complication of TB, with movement disorders representing an under-recognized yet impactful manifestation. Despite their clinical significance, knowledge gaps persist in epidemiology, pathophysiology, and management of TB-related movement disorders (TBRMDs). This scoping review synthesizes evidence on TBRMDs, aiming to characterize their spectrum, evaluate diagnostic approaches, and summarize management strategies and outcomes. Following PRISMA-ScR guidelines, a systematic search of PubMed, EMBASE, and Scopus (final search: December 31, 2024) identified studies of all designs and languages reporting movement disorders in CNS TB. Data extraction, quality assessment (Joanna Briggs Institute tools), and thematic synthesis were conducted. Of 36 included studies (91 cases), tremor (27.5%), chorea (26.4%), and dystonia (16.5%) were most prevalent. Tremor predominated in tuberculous meningitis (48.9%), while chorea was common in tuberculomas (42.3%). Lesion location correlated with phenomenology: basal ganglia lesions linked to chorea/dystonia, cerebellar involvement to ataxia. Pathogenesis included meningitis (54.9%), tuberculomas (32.9%), and vasculitis (8.8%). Treatment with anti-tubercular therapy and corticosteroids resulted in complete resolution in 43.9% of cases, but 32.9% showed no improvement. Geographically, South America (61.8%) and Asia (19.7%) reported most cases, with a temporal surge post-2000. TBRMDs are heterogeneous in presentation, linked to lesion location and pathogenic mechanisms. Early recognition, multimodal management, and neuroimaging are critical. Significant variability in diagnostic and reporting standards highlights the need for consensus criteria and prospective studies, particularly in high-burden regions. This review underscores the need of global collaborations to optimize clinical care and advance research in this neglected domain.

Over the last decade, several clinical reports have outlined cases of early-onset manganese (Mn)-induced dystonia-parkinsonism, resulting from loss of function mutations of the Mn transporter gene SLC39A14. Previously, we have performed characterization of the behavioral, neurochemical, and neuropathological changes in 60-day old (PN60) Slc39a14-knockout (KO) murine model of the human disease. Here, we extend our studies to aging Slc39a14-KO mice to assess the progression of the disease. Our results indicate that 365-day old (PN365) Slc39a14-KO mice present with markedly elevated blood and brain Mn levels, similar to those found in the PN60 mice and representative of the human cases of the disease. Furthermore, aging Slc39a14-KO mice consistently manifest a hypoactive and dystonic behavioral deficits, similar to the PN60 animals, suggesting that the behavioral changes are established early in life without further age-associated deterioration. Neurochemical, neuropathological, and functional assessment of the dopaminergic system of the basal ganglia revealed absence of neurodegenerative changes of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), with no changes in DA or metabolite concentrations in the striatum of Slc39a14-KO mice relative to wildtype (WT). Similar to the PN60 animals, aging Slc39a14-KO mice expressed a marked inhibition of potassium-stimulated DA release in the striatum. Together our findings indicate that the pathophysiological changes observed in the basal ganglia of aging Slc39a14-KO animals are similar to those at PN60 and aging does not have a significant effect on these parameters.