A woman in her late 40s presented with a 1 year history of progressive symmetrical rest tremor, bradykinesia, rigidity, hypophonia and postural instability (Movement Disorder Society-sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III 41) without musculoskeletal symptoms or family history. Routine investigations were unremarkable except low-normal serum alkaline phosphatase (41 U/L, range 35-104), mild anaemia and vitamin D insufficiency; brain MRI showed blooming in bilateral globus pallidi. Minimal to no improvement observed at 1 month on modest dopaminergic dosing (MDS-UPDRS III 38). Whole-exome sequencing identified a heterozygous pathogenic frameshift variant c.388del (p.Val130Cysfs*1) in ALPL (alkaline phosphatase, liver/bone/kidney) gene. In the absence of classical skeletal features and without substrate testing, this finding is suggestive of a possible mild adult hypophosphatasia phenotype. This case highlights a potential association between ALPL variants and parkinsonism and underscores the role of genetic testing in atypical presentations.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions that cause abnormal postures or repetitive movements. Isolated lingual dystonia (ILD) is a rare form of oromandibular dystonia, which affects only the tongue and accounts for about 4% of all dystonia cases. This report describes two Filipino males, aged 43 and 48, who developed ILD. The first patient is a 43-year-old male from Cebu, with no significant family history or roots from Panay Island, who was found to carry the X-linked dystonia parkinsonism (XDP)-causing variant highlighting a novel presentation of ILD linked to XDP. The second patient is a 48-year-old male from Roxas City, with a family history suggesting XDP, who presented with ILD initially and later developed tremor, limb dystonia, and bradykinesia. His diagnosis of XDP was confirmed by genetic testing. These cases highlight the importance of considering XDP in the differential diagnosis of ILD among Filipinos, regardless of geographic or familial predispositions. Genetic testing and follow-up examinations are crucial for managing ILD, as it may precede more generalized dystonic and parkinsonian symptoms associated with XDP. This study contributes to the limited literature on ILD and suggests new insights into the clinical variability of XDP.

Lung cancer is the leading cause of cancer-related death worldwide. In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutations are predictive biomarkers of a high response to tyrosine kinase inhibitors (TKIs). Osimertinib is the TKI of choice due to its efficacy in controlling central nervous system disease. Holmes tremor is a low-frequency, irregular tremor that may occur at rest, posturally, or during action. The lesions causing this syndrome are not confined to a single brain region but involve functionally connected circuits. Its occurrence secondary to brain metastases is rare, and response to osimertinib has not been previously reported. We present the case of a 35-year-old, nonsmoking woman with stage IVB NSCLC harboring an EGFR exon 19 mutation and brain and bone metastases. During the course of her illness, she developed a progressive upper-extremity and head tremor consistent with Holmes tremor. She was treated with dexamethasone and whole-brain radiotherapy. Following initiation of osimertinib, marked clinical improvement was observed within 4 weeks. Ninety days later, a brain MRI demonstrated partial remission of the lesions. Holmes tremor is a heterogeneous clinical entity, and its management typically relies on nonspecific medications with variable efficacy. This case represents, to our knowledge, the first reported instance of Holmes tremor associated with EGFR-mutated NSCLC showing a favorable response to osimertinib.

Although Lansoprazole, a proton pump inhibitor, is quite safe, there have been occasional reports of associated neurological dysfunction. We present a middle-aged man who developed bilateral asterixis within few hours of the first dose of lansoprazole. Interestingly, the jerks disappeared rapidly after discontinuation of lansoprazole.

Aerobic exercise programs with proprioceptive sensory feedback elements such as split-belt treadmill training, perturbation treadmill training, and dynamic cycling improve function in people with Parkinson's disease (PwPD). However, these tools are expensive and not highly accessible. Speed-variable (SV) treadmill training utilizes small-amplitude treadmill belt speed fluctuations every 10-60 s, emulating aforementioned paradigms in a more-accessible design targeted toward home or gym settings. Fourteen PwPD (67.6 ± 6.5 years, 6 female) completed one 30-min session of SV training and one 30-min session of normal (N) non-speed-varied treadmill training in a counterbalanced design. Motor function was assessed pre- and postexercise with KinesiaONE inertial measurement unit validated for assessment of symptoms including tremor, bradykinesia, rhythm, and amplitude of movement. Heart rate (HR) did not differ significantly (p = 0.146, t = -1.102) across conditions, with average HR in 60%-65% age-predicted HRmax range. Rating of perceived exertion (RPE) was significantly (p = 0.020, t = 2.274, effect size 0.608) lower in SV condition than N condition by 0.8 points on the 6-20 Borg scale. Generalized linear mixed model analysis revealed significant interaction effects in sum hand motor function, bradykinesia and tremor sum, and resting and postural tremor items (p < 0.05), driven by improvements in symptoms post-SV exercise. No significant interactions were observed for hand amplitude, rhythm of movement, or lower body symptoms. Overall, data support SV treadmill training as an exercise paradigm for PwPD to acutely impact hand motor function utilizing a standard treadmill. Future work should evaluate multiple sessions of training and evaluate dose-response effect of speed variability.

Canine paroxysmal dyskinesia is an episodic movement disorder characterized by transient dystonia, dyskinesia and tremor in dogs with preserved consciousness, yet its differentiation from focal epilepsy remains challenging and a structured diagnostic framework comparable to that used in epilepsy is lacking.

BackgroundCognitive impairment and neuropsychiatric manifestations are common disabling non-motor symptoms that can negatively impact quality of life in Parkinson's disease. This review aimed to critically appraise and synthesize evidence on the prevalence, predictors, and emerging biomarkers of cognitive impairment and neuropsychiatric manifestations among patients with Parkinson's disease in Africa.MethodsWe conducted a systematic review of studies reporting cognitive and neuropsychiatric outcomes among individuals with Parkinson's disease in African populations, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We used the Critical Appraisal Skills Program checklist to determine the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to estimate the certainty of the evidence.ResultsA total of 32 studies, including 3687 patients, were analyzed. The prevalence of cognitive impairment ranged from 21.6% to 92%. Depression was the most common neuropsychiatric symptom (up to 81.7%). Consistent predictors of cognitive impairment included older age, advanced disease, and greater motor severity. Importantly, APOE ε4 homozygosity was associated with a twofold increase in the risk of cognitive impairment, while findings on LRRK2 G2019S mutations were heterogeneous across populations. Additionally, hypocalcemia and retinal nerve fiber layer thinning were linked to worse cognitive outcomes. Functional neuroimaging studies revealed altered emotional processing, with enhanced activation of limbic and cortical networks in response to positive emotional stimuli.ConclusionsEvidence from this review suggests that cognitive impairment and neuropsychiatric manifestations are common in African PD populations and may be associated with clinical, genetic, metabolic, and neurobiological factors, although the quality of the evidence is low. Larger, community-based, and longitudinal studies are warranted.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis typically presents with psychiatric symptoms, seizures, and cognitive dysfunction. Movement disorders, when present, usually coexist with these features. We report a rare case of anti-NMDAR encephalitis in a 30-year-old female who presented with isolated left temporomandibular joint (TMJ) dystonia, jaw tremor, and facial pain as the sole manifestations for seven months, without clinically significant psychiatric, cognitive, or seizure symptoms. The patient was repeatedly misdiagnosed with TMJ disorder and muscular dysfunction before anti-NMDAR IgG antibodies were detected by cell-based assay (CBA) in serum (1:32) and cerebrospinal fluid (CSF, 1:1). First-line immunotherapy with intravenous immunoglobulin (IVIG) achieved remission. However, she relapsed five months later following COVID-19 infection, with antibody titers rising to 1:100 in both serum and CSF. High-dose corticosteroid pulse therapy and maintenance mycophenolate mofetil were administered, achieving sustained clinical improvement over four years of follow-up, although mild residual focal dystonia persisted. Whole-exome sequencing and hereditary ataxia screening excluded genetic causes. This case broadens the clinical spectrum of anti-NMDAR encephalitis and underscores the importance of early antibody testing in young patients with treatment-refractory orofacial movement disorders.

The high-intensity focused ultrasound (HIFU) technique has become precise, incisionless, and ablative for treating essential tremor (ET) and Parkinson's disease (PD), driven by advances in magnetic resonance imaging (MRI) thermometry and tractography. The current review integrates the main clinical outcomes associated with established and emerging HIFU targets, synthesizing efficacy data, adverse effect (AE) patterns, and procedural characteristics relevant to clinical decision-making. In ET, ventral intermediate nucleus (VIM) thalamotomy results in tremor reductions ranging from 56 to 81%, with a long-term sustained benefit of approximately 73%. In tremor-dominant PD (TdPD), VIM ablation achieves tremor suppression of approximately 62%. Comparatively, HIFU-guided subthalamotomy provides broader motor benefits, with 53 to 57.8% improvement in the Movement Disorder Society's Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS III), as well as significant reductions in rigidity and bradykinesia. Pallidotomy improves "off" state motor symptoms and dyskinesias, whereas pallidothalamic tractotomy leads to 52% global motor improvement and 91% tremor reduction. The AEs vary according to the targets. In VIM procedures, gait imbalance (16-40%) and sensory disturbances (9-26%) predominate, along with dysarthria and dysmetria. Lesions to the subthalamic nucleus (STN) are most commonly associated with dysarthria (10-26%) and gait instability (15-48%). Procedures targeting the globus pallidus internus (GPi) or pallidothalamic tract (PTT) may also present with gait instability or dysarthria, which are generally mild and transient. Although the SDR has historically limited eligibility, recent evidence demonstrates that patients with SDR ≤ 0.40 may still experience meaningful improvement, supporting more individualized selection. In the current therapeutic landscape, HIFU offers immediate clinical benefits, absence of implanted hardware, and simplified recovery, positioning it as an alternative or complementary therapy to deep brain stimulation (DBS).