Raymond L. Rosales

Integrating research into medical education is very important. Despite demanding academic schedules, medical students can develop essential research skills through structured opportunities, faculty mentorship, and progressive engagement in clinical and translational research. Medical schools must recognize research as a fundamental component of physician development, empowering future clinicians to question existing knowledge, generate evidence, and advance medical practice.

Background and Objectives: X-linked dystonia-parkinsonism (XDP) is a severe neurodegenerative movement disorder caused by a retrotransposon insertion with a polymorphic hexanucleotide repeat expansion in the TAF1 gene. While the disease predominantly affects males, female carriers may exhibit a variable phenotypic expression. Neurobiological alterations in asymptomatic female mutation carriers (fMC) remain largely unexplored. We aimed to investigate whether fMC exhibit neurodegenerative changes despite the absence of overt clinical manifestations and to assess their clinical, genetic, and longitudinal correlates using multimodal MRI. Methods: In this cross-sectional and longitudinal multimodal study, 103 female relatives of XDP patients underwent clinical, genetic, and MRI assessments. Forty-two were identified as fMC and 61 as healthy controls (HC). Structural T1-weighted MRI was analyzed using voxel-based morphometry and subcortical volumetry, while susceptibility-weighted imaging assessed iron deposition. Clinical evaluation included standardized motor and cognitive testing. Longitudinal follow-up MRI was available for a subset of participants (20 fMC, 13 HC). Results: fMC exhibited significant striatal atrophy compared to HC, with volume reductions in the caudate (-19.4%), putamen (-18.6%), and pallidum (-28.6%) (all p<0.001), despite the absence of overt movement disorders or cognitive deficits, accompanied by relative cerebellar hypertrophy. In fMC striatal volumes decreased with increasing age (putamen: rho=−0.382, p=0.012; caudate: rho=−0.631, p<0.001) and virtual time from genetically determined estimated age at onset (putamen: rho=−0.406, p=0.008; caudate: rho=−0.660, p<0.001). Susceptibility-weighted imaging revealed increased iron deposition in the caudate in fMC, which increased with greater local atrophy (rho=0.718, p<0.001). No significant longitudinal progression was detected over follow-up intervals of up to 25.5 months. Discussion: Asymptomatic female carriers of the XDP-associated TAF1 variant exhibit significant striatal neurodegeneration and iron accumulation, indicating a dominant-negative effect despite X-linked inheritance. Future longitudinal studies should focus on non-motor features and integrate genetic, imaging, and clinical markers to improve risk stratification and identify the subset of female carriers most likely to benefit from future disease-modifying therapies.

THAP1-associated dystonia (DYT-THAP1) is classically described as an early-onset disorder with craniocervical involvement and potential for generalization. However, increasing reports suggest a broader phenotypic spectrum, including adult-onset presentations. We aimed to characterize the clinical phenotype of genetically confirmed DYT-THAP1 with age at onset ≥ 40 years, and to highlight an illustrative case. A scoping review was conducted following Joanna Briggs Institute methodology. Comprehensive searches of PubMed, MDSGene, Google Scholar, and regional databases identified studies reporting patient-level clinical data in individuals with genetically confirmed THAP1 mutations and late-onset disease. Data on age of onset, site of onset, distribution, sex, family history, mutation geste antagoniste were extracted and synthesized descriptively. Twenty-two studies comprising 50 patients met the set inclusion criteria. Cranial dystonia was the most common site of onset (n = 22), followed by cervical (n = 13), while limb onset was uncommon. Most patients presented with segmental distribution (n = 27), followed by focal (n = 20), and only 3 cases demonstrated generalized involvement. The majority of cases were sporadic (37/50). Associated clinical features and geste antagoniste were infrequently and inconsistently reported across studies. We additionally present a Filipina with late-onset focal lower limb dystonia, further highlighting an atypical pattern of limb onset. Collectively, these findings suggest that late-onset THAP1-associated dystonia may exhibit a phenotype distinct from classical early-onset presentations characterized by cranial and cervical predominance, segmental distribution, and frequent sporadic occurrence. Recognition of this broader phenotypic spectrum may facilitate consideration of genetic etiologies in adult-onset dystonia, even in the absence of a family history.

Movement disorders associated with neuromuscular diseases are often underrecognized, yet they represent a distinct clinical entity. Abnormalities in areas of the peripheral nervous system, i.e., nerves and muscles, can stem from dysfunction of ion channels and proteins involved in membrane excitability. Hyperexcitability of peripheral motor nerves presents as cramps, stiffness, abnormal posture and gait, as well as changes in motor unit potentials during electromyography studies; hence, it may be classified as a movement problem. Etiologies range from hereditary, immune-mediated, or may be secondary to structural changes. This review focuses on peripheral nervous system and muscle-derived movement disorders associated with autoantibodies. It aims to highlight immune-mediated peripheral nerve hyperexcitability syndromes, stiff-person spectrum disorders, and immune-mediated rippling muscle disease (a movement disorder of muscular origin). It also discusses pathophysiology, diagnosis (particularly immunologic markers), and therapeutics.

Botulinum toxin (BoNT) is established as a first-line treatment for focal and segmental dystonias, yet longitudinal real-world data on its efficacy and barriers to care in resource-limited settings like the Philippines remain scarce. The objective of this study was to describe the five-year clinical outcomes, safety profile, and socioeconomic barriers to treatment continuity among patients with X-linked Dystonia-Parkinsonism (XDP) receiving BoNT injections. We conducted a retrospective descriptive study of 159 genetically confirmed XDP patients (558 injection sessions) at a tertiary center from 2021 to 2025. Besides pedigree confirmation and adequate follow-up data extraction, at least two cycles of BoNT were mandated. Outcomes were evaluated using the Global Dystonia Rating Scale (GDRS), Patient Global Impression of Improvement (PGI-I), and treatment-related adverse events (TRAE). Muscle localization was mainly achieved using electromyography (EMG) and/or ultrasound (US) guidance. There were 558 unique injection sessions and each XDP patient came for 2-8 sessions. The anatomical areas injected were cervical (49%), oromandibular/lingual (32%), facial (18%), upper/lower limb (15%), and truncal (8%). The overall mean GDRS improvement was 65.5% at four weeks post-injection. The highest clinical responses by region were observed in facial (69.6%) and focal upper/lower limb (64.7%) dystonias, followed by oromandibular/lingual (55.6%), cervical (55.6%), and truncal involvement (48.9%). Overall, the mean PGI-I score was 2.4 ± 0.6 ("Much better") in all combined regions injected. TRAEs occurred in 30% of patients and included dysphagia, localized muscle weakness, bruising, and pain. Financial constraints were the leading barrier to reinjection (53%), followed by distance or travel difficulties (33%) and pandemic-related disruptions (24%). BoNT therapy is an effective and safe intervention for XDP, across various dystonic regions, including drooling. While precision targeting through instrumentation optimizes outcomes, significant socioeconomic barriers persist, highlighting the need for sustainable funding models to maintain functional stability in this vulnerable population.

Parkinson's disease (PD) is classically defined by its motor manifestations, yet its negative psychosocial impact remains underrecognized. Facial bradykinesia, or hypomimia, restricts patients' primary channel for nonverbal communication, potentially establishing a substantial barrier to social connection and relationship maintenance. This scoping review maps the literature concerning the interpersonal and psychosocial outcomes of hypomimia in adults with PD. Following Joanna Briggs Institute (JBI) methodology and PRISMA-ScR guidelines, we systematically searched PubMed, Europe PMC, Semantic Scholar, and Google Scholar databases. Rigorous screening against predefined eligibility criteria yielded 14 primary studies for thematic data extraction and narrative synthesis. Hypomimia operates as a "dual-blind" communication barrier. Internally, it disrupts the "emotional mirror" mechanism; impaired physical mimicry is associated with a diminished capacity for patients to recognize others' emotions. Externally, the mask frequently elicits character misidentification; observers and even healthcare professionals frequently misjudge patients as apathetic, depressed, or cognitively impaired. Female patients often experience heightened stigmatization due to violated gender norms. Domestically, this can create an "invisible wall," contributing to spousal misinterpretation and negatively impacting caregiver relationship satisfaction. Crucially, perceived stigma serves as a primary clinical mediator of diminished quality of life (QoL) than depression alone. Furthermore, facial masking disrupts the bidirectional relationship between social environments and emotional expression. Hypomimia is a significant contributing factor to psychosocial isolation. Comprehensive PD management must transcend motor-centric therapies to incorporate caregiver education, clinical bias-awareness training, and emotion-recognition rehabilitation.

In the original publication of this article

Background: Neuromuscular and movement disorders comprise a heterogeneous group of acquired and inherited conditions affecting the motor unit and central movement pathways. Genetic data from underserved populations, including Filipinos, remain limited, highlighting the need for population-specific characterization. Objective: To characterize inherited neuromuscular and movement disorders among Filipinos and determine the diagnostic yield and genetic spectrum using next-generation sequencing (NGS). Methods: This referral single-center retrospective study reviewed Filipino patients who underwent genetic testing for suspected inherited neuromuscular and movement disorders. Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Results: Among 85 patients, 24 (28.2%) had pathogenic/likely pathogenic variants, 33 (38.8%) had variants of uncertain significance (VUS) and 28 (32.9%) were negative. Confirmed diagnoses included pediatric cases of limb-girdle muscular dystrophy, Duchenne muscular dystrophy, spinal muscular atrophy and GNE-related myopathy, and adult cases with myofibrillar myopathy, spinocerebellar ataxia and amyotrophic lateral sclerosis. Pathogenic variants involved 26 genes, most commonly SMN1. Conclusion: This NGS-based characterization of inherited neuromuscular and movement disorders in Filipinos showed 28% diagnostic yield and a spectrum comparable to other Asian cohorts. The high rate of VUS underscores the need for family segregation studies and careful genotype–phenotype correlation. This study highlights the critical role of genetic testing in accurate diagnosis and targeted management to improve outcomes for patients with these rare disorders.