Cerebellar ataxias are a diverse group of hereditary and acquired disorders that impair balance, gait, posture and ocular movements. With limited treatment options, particularly in hereditary forms, neuromodulation has emerged as a promising therapeutic approach particularly the transcranial direct current stimulation (tDCS). This scoping review aims to discuss the role of tDCS as a potential therapy in reducing ataxia symptoms in both hereditary and acquired forms. A total of 787 studies were found after searching Pubmed, EMBASE, and Cochrane. After removing 273 duplicates, 514 studies remained for title and abstract screening. Of these, 387 studies were excluded, leaving 127 studies for full-text assessment. Following retrieval of full text, 26 was assessed for eligibility. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive literature search was performed using PubMed, EMBASE, and Cochrane databases. Two independent reviewers screened studies through title/abstract and full-text review, with disagreements resolved by discussion or adjudication by two additional reviewers when necessary. We included 18 studies for the final analysis. Most studies reviewed showed that tDCS is a potential option for the treatment of ataxia, however, differences among participants, neuromodulation techniques, or trial protocols may have led to differences in the clinical outcomes. Our review highlights that the vast majority of the randomized controlled studies of tDCS in neurodegenerative ataxias have demonstrated clinical beneficial effect. There are preliminary observations that tDCS in combination therapy with rehabilitation or exercise may provide greater or more functional improvements. Future multicenter studies with long term follow up of individual disease groups, supported by clinical, imaging and biological marker measurements will help address the current limitations.

Myoclonus is a hyperkinetic movement disorder characterized by sudden, brief involuntary movements that are shock-like and/or jerky. Positive myoclonus is generated by abrupt muscular contractions, which occur synchronously in the affected body part, while negative myoclonus, also referred to as asterixis, results from a brief interruption or silencing of muscle activity leading to a sudden movement due to loss of muscle tone. Myoclonus manifests across a highly heterogeneous group of neurologic and systemic disorders. Due to its varied clinical presentations and multiple etiologies, diagnosing and managing myoclonus in clinical practice remains challenging. The authors retrieved publications that focus on myoclonus as a movement disorder from various electronic databases. The included articles contained discussion on clinical or electrophysiologic findings of myoclonus and its classification. This review outlines a practical diagnostic guide for clinicians that includes consideration of the newly developed 2025 International Association of Parkinsonism and Related Disorders (IAPRD) Axis classification system. This consensus-based framework organizes the diagnostic process into clinical features (Axis 1 A), clinical neurophysiology (Axis 1B), and etiology (Axis II). By systematically evaluating historical data, physical examination findings, and ancillary tests, clinicians can successfully arrive at a clinical syndrome which helps guide investigations to determine the underlying etiology. Neurophysiological assessments are important in determining the specific neuroanatomic generator (cortical, cortical-subcortical, subcortical, brainstem, spinal, propriospinal, peripheral). Categorizing myoclonus by its physiological subtype ultimately dictates the most effective symptomatic treatments. While resource-limited settings may necessitate a primarily clinical approach, employing this step-by-step localization aids in avoiding unnecessary testing and ensures optimal patient care.

Schizophrenia patients with depressive symptoms may represent a distinct clinical subtype with unique metabolic features. This study investigated divergent metabolic-psychopathological patterns in first-episode drug-naïve schizophrenia (FEDN-SCZ) patients stratified by depressive symptoms. We recruited 289 FEDN-SCZ patients and 128 healthy controls. Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and depressive symptoms were evaluated with the 24-item Hamilton Depression Rating Scale (HAMD-24). Patients were stratified into subgroups based on HAMD-24 cut-off scores. Metabolic parameters, including uric acid (UA), fasting glucose, glycated hemoglobin (HbA1c), fasting insulin, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol, were systematically measured. FEDN-SCZ patients exhibited marginally higher UA levels than healthy controls (p = 0.050), with elevated levels observed in patients with depressive symptoms compared to those without (351.41 vs. 317.64 µmol/L, p = 0.047). The UA-PANSS association was moderated by depressive status (significant interactions for negative, general, and total PANSS scores, all p < 0.05), with simple slopes significant only in the depression group. Multiple regression analyses revealed subgroup-specific predictors: in the depressive subgroup, higher UA was associated with greater symptom severity, while HDL-C showed a protective effect; in non-depressive patients, glycemic indices (HbA1c and glucose) emerged as significant predictors (p < 0.05). The UA-psychopathology association was exclusive to FEDN-SCZ patients with depressive symptoms, while non-depression patients were characterized by glucose and energy dysregulation. These findings underscore the importance of stratified management strategies addressing both psychiatric and metabolic health.

The differential diagnosis between degenerative cervical myelopathy (DCM) and early amyotrophic lateral sclerosis (ALS) is often clinically challenging; laboratory tests that support this distinction could be highly valuable. This study examined the concentrations of neurofilament light chain (NfL) and the phosphorylated neurofilament heavy chain (pNfH), in CSF and serum of carefully selected patients with DCM, spinal canal stenosis (SCS) and ALS, after exclusion of major neurological confounders. Patients were assigned to five groups according to MRI findings and ALS diagnosis. All patients were treated in the Department of Neurology, and were only included if a CSF or serum sample was available for retrospective measurement of neurofilaments. Z-scores were used for age-adjusted interpretation of NfL concentrations in CSF and serum. In addition, the albumin quotient (QAlb), as a marker for the integrity of the blood-CSF barrier, was investigated in the five patient groups. The levels of NfL and pNfH, including Z-score distributions, differed significantly. The groups with diagnosed ALS had elevated neurofilaments both in CSF and Serum. Comparison of neurofilament concentrations between patients with isolated spinal canal stenosis and patients with cervical myelopathy revealed no significant difference. The QAlb showed no clear correlation with elevated neurofilaments and provided limited value for differential diagnosis. In summary, we showed that NfL and pNfH in CSF and serum support the differential diagnosis of cervical SCS with and without myelopathy from ALS in carefully selected cohorts. However, since neurofilaments are not specific, they should be used in context with clinical assessment and imaging for individual diagnostic and treatment decisions.

Language abilities in autism show considerable variability across linguistic domains: vocabulary, grammar/structural language, and pragmatics (language in context) may be affected to differing degrees and not always simultaneously, as is the case in other neurodevelopmental conditions (NDCs), e.g. Down syndrome, Williams syndrome, or Developmental Language Disorder. This selective review synthesises empirical markers of language impairment across linguistic domains in autism, sometimes in comparison to other NDCs, while also evaluating theoretically driven assessment tools, both established and currently under development, that implement these markers. Core linguistic markers across the autism spectrum include 'social pragmatic' difficulties, i.e. challenges with irony comprehension, referential expression use, and narrative coherence. Impairment in grammar/structural language, such as morphosyntax (e.g., tense marking, passives, relative clauses) and phonology (e.g., consonant clusters, as in str), is observed in a substantial subset of autistic individuals and many other NDCs. Aspects of 'linguistic pragmatics,' such as understanding metaphor and indirect requests, tend to be impaired mainly in autistic individuals who also have structural language difficulties. Other challenges have been reported, including in prosody, semantics and lexical-pragmatics (e.g., mental state terms such as think, fear, happy), but remain underexplored. We further evaluate several existing and emerging screening tools that target specific linguistic markers and accommodate a wide range of populations, including males and females, multilingual speakers, minimally speaking individuals, and those with varying intellectual abilities. Grounded in theoretical linguistics, these tools are designed to facilitate detailed profiling of language strengths and challenges in autism. Their cross-linguistic design and applicability make them well-suited for cross-syndrome comparisons and the development of tailored interventions.

Depression with a prevalence between 20% and 86% and anxiety with a prevalence up to 72% most frequently coexist with vascular dementia (VaD) and reciprocally increase disease risks. Both psychopathological disorders are usually more frequent and more severe in patients with VaD than in those with Alzheimer disease (AD). Although there is a significant association between depression and all-cause dementia, VaD with depression has more comorbidities and higher mortality than without depression. A history of depression prior to dementia is more common than in AD, while its pre-disease state is a matter of discussion. Although the diagnosis of depression related to cerebrovascular disorders is based on the criteria of DSM-V, VaD/depression has been suggested to be a distinct subtype differing from late-life depression and major depressive disorder, whereas others reported broadly similar depressive symptom profiles across VaD, AD, and AD plus VaD. Depression in the course of VaD, which is frequently underdiagnosed and undertreated, has been related to a variety of pathogenic mechanisms, in particular cerebral small vessel disease (CSVD), cerebral white matter lesions, damage to fronto-subcortical brain circuits, neuroinflammation, impaired neurotrophic support, and imbalance of neurotransmitter/kynurenine pathways. Multimarkers, like high CSVD and white matter hyperintensity burden, the presence of visible perivascular spaces, inflammatory markers, neurofilament light chain levels, and other biomarkers may support clinical diagnosis of VaD/depression. Treatment planning should consider a modest response to antidepressants, while treatment of vascular and metabolic comorbidities may provide promising targets for its prevention and treatment. Electroconvulsive therapy and transcranial direct current stimulation as augmentation treatment of an adequate pharmacotherapy are potential strategies in the management of VaD/depression that is known to be often unresponsive to antidepressants only. However, their effectiveness needs further investigation to assess which interventions are appropriate and effective in clinical practice.

Genetic testing is traditionally emphasized in early-onset or familial Parkinson's disease (PD), leaving its role in advanced disease uncertain. This mini-review explores, from the perspectives of patients, their family members, and clinical researchers, whether genetic investigation remains meaningful once patients reach advanced PD. In large prospective clinical-genetic screening cohorts, roughly one in seven PD patients has genetic PD. Established genotype-phenotype correlations, spanning cognitive trajectory, levodopa responsiveness, and deep brain stimulation outcomes, continue to inform clinical decision-making even at advanced stages. Thus, patients may gain psychological clarity, receive refined prognostic counseling, and become eligible for gene-specific trials or registries. In addition, patients express altruistic motivations, considering the merit of sharing their genetic testing results with their families and the research community. Unaffected relatives may benefit from more precise, penetrance-informed risk assessment, appropriately scaled surveillance, lifestyle counseling, and reproductive planning, particularly as potential environmental modifiers of penetrance and age at onset become better characterized. Researchers rely on genetically characterized advanced-stage cohorts to identify genotype-phenotype relations, modifiers of onset, progression and treatment response, validate biomarkers, and build the large, deep longitudinal datasets required for emerging gene- and pathway-targeted therapies. Collectively, these perspectives argue against a narrow early-disease "window of opportunity" for genetic testing in PD. Rather than becoming obsolete once the disease reaches a more advanced stage, genetic characterization continues to shape individualized care, family counseling, and translational research. Thus, in the future, the challenge should no longer be to justify genetic testing in advanced PD, but to embed it equitably and systematically within standard care and international research infrastructure across the entire disease course.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with increasing global prevalence, yet comprehensive qualitative research on patient experiences in the Philippines remains scarce. Understanding the lived experiences and unmet needs of Filipino PD patients is essential for developing culturally appropriate interventions. This phenomenological study aimed to characterize the patient journey and identify the unmet clinical, informational, and psychosocial needs of individuals living with Parkinson's disease in the Philippines through analysis of social media narratives. A qualitative descriptive phenomenological design was employed, utilizing social media listening techniques to systematically retrieve and analyze publicly accessible posts from Facebook, YouTube, Reddit, and Twitter/X. Purposive sampling yielded 200 posts authored by self-identified Filipino PD patients and caregivers from January 2023 to April 2026. Data were analyzed using phenomenological thematic analysis. The analysis revealed that the Filipino PD experience is characterized by "navigating the Parkinson's maze"-a journey through interconnected physical, financial, geographic, and systemic challenges. The most pervasive theme was economic hardship, with patients describing medication costs reaching ₱15,000 monthly, chronic stock-outs, and difficult choices between medications and basic necessities. Significant diagnostic delays, limited access to neurologists outside Metro Manila, inadequate multidisciplinary care, and severe caregiver burden were also identified. Social media emerged as a vital platform for information exchange, emotional support, and advocacy. The social media narratives reflected unique challenges shaped by healthcare system limitations, economic constraints, and geographic disparities. Findings underscore the urgent need for expanded medication access, government support programs, integration of multidisciplinary care, and recognition of social media as a valuable patient support resource.

Essential tremor (ET) is a complex disorder extending beyond upper limb action tremor. Both slowing in upper limb movements and impaired gait performances have been widely described. The present study aimed to assess clinical-instrumental relationship between wearable-sensor recorded upper limb motility, tremor and walking performances in ET and explore their role in disease characterization. A gyroscope taped over the index finger was used to quantify both tremor in three tasks (forward outstretched; lateral-wing; instrumental finger-nose, iFN) and upper limb performances in the iFN. Maximum speed (MS) and time (going phase; approaching phase) were used as indices of upper limb motility. Explorative correlation analyses were used to assess the relationship between walking and upper limb metrics. Regression analysis - using synthetic indices of walking (WPC1) and turning performances (TPC1) obtained with PCA - were applied to confirm the association adjusting for possible confounders. Thirty patients were considered for the analyses (23 men, 76.7%; mean age ± SD: 71.9 ± 5.1). No significant correlation between tremor and kinematic parameters was found. Consistent correlations were found between upper limb kinematics and gait performances. Both WPC1 and TPC1 were significantly associated with MS. The study identified an association between upper limb motor performances and gait dynamics in ET, suggesting a possible expression of a shared motor-control pathway, at least partly independent from the tremor network. Moreover, the potential role of a simple, rapid and clinically-scalable, wearable sensor-based protocol applicable both in tremor quantification and as a potential marker of broader motor function in ET was also highlighted.

Activation of the NLRP3 inflammasome pathway and dysfunction of brain-derived neurotrophic factor (BDNF) are both implicated in the pathogenesis of Alzheimer's disease (AD). While in vitro and in vivo models support these mechanisms, there is little research investigating their relationship in human brain tissue, and whether this relationship may be abnormal in the AD brain. Temporal cortex tissue taken post-mortem from AD patients and control subjects was analysed for expression of genes for the NLRP3 pathway (NLRP3, PYCARD, CASP1), the potassium channel THIK1 (KCNK13), and related pro-inflammatory cytokines (IL-1β, IL-18). BDNF mRNA expression and DNA methylation in the BDNF exon IV promoter were determined. Correlations between these BDNF measures and NLRP3-related genes were investigated. A significant relationship between BDNF mRNA expression and mean methylation was observed in control subjects but not in AD. In controls, significant correlations with both BDNF expression and mean BDNF methylation were observed for NLRP3, CASP1 and IL1B. These correlations were lost in the AD group, which also showed a significant correlation of KCNK13 expression with both BDNF measures, not seen in controls. This study indicates that the relationship between BDNF and NLRP3 activation, as measured by NLRP3 inflammasome components and proinflammatory cytokine products, is disrupted in AD. The contrary correlation emerging in AD between BDNF measures and KCNK13 expression, shown to be elevated in AD, indicates the possible relationship of this finding with BDNF dysfunction. These findings enhance our understanding of AD pathophysiology, demonstrating the importance of understanding the neuroinflammatory-neurotrophic balance in neurodegenerative processes.

Opicapone (OPC) is an effective add-on medication for motor fluctuations in Parkinson's disease (PD), with a favorable safety and tolerability profile. Elderly PD patients are a great proportion of the real-world PD population, often underrepresented in clinical trials. This multicenter, retrospective, longitudinal study aimed to assess the real-world safety and tolerability of OPC in PD patients aged ≥ 65 years. Clinical-demographic data were collected at OPC initiation (T0) and at the last follow-up visit (T1). OPC-related adverse events (AEs) and reasons for discontinuation were recorded. Patients were compared according to age and treatment continuation. Logistic regression analyses were used to evaluate association between baseline features and occurrence of AEs and discontinuation. One-hundred and one elderly PD patients were included and followed up for 20.6 ± 18.8 months after OPC initiation. Overall, 49 patients (48.5%) reported AEs, and OPC was discontinued in 29 (28.7%) within 9.4 ± 15.3 months, with neuropsychiatric and cardiovascular/autonomic AEs being the most common reasons. Patients aged ≥ 75 years reported greater disease severity and frequency of AEs compared to younger patients, but similar discontinuation rates at follow-up. At T1, OPC discontinuers exhibited greater motor impairment and a lower total levodopa equivalent dose. Univariate analyses showed that age, disease stage, and comorbidity burden were significantly associated with AEs occurrence. In the multivariable analysis, disease stage remained the only significant baseline feature associated with AEs. OPC was generally well tolerated in this cohort of real-world elderly PD patients. Larger, prospective studies are warranted.

In Parkinson's disease (PD), the limitations in disease-modifying therapies have broadened the concept of neuroprotection beyond targeting specific pathogenic pathways to include the strengthening of motor reserve and resilience through modifiable lifestyle factors. This review synthesizes current evidence on lifestyle medicine for PD, focusing on its potential contribution to neuroprotection, symptom control, and implementation in Asian contexts. We first discuss physical activity and exercise, including community-based and technology-assisted approaches, as interventions that improve motor and non-motor outcomes and may have long-term disease-modifying potential. We then review nutrition from prevention-oriented, genetic, and disease-stage-specific perspectives, including dietary patterns, caffeine and tea exposure, and nutritional vulnerability in established PD. Sleep health and stress management are considered as interconnected determinants of daily function, quality of life (QoL), and resilience. We further discuss integrated lifestyle medicine as a multidomain care model that combines core lifestyle pillars with personalized, sustainable, and culturally responsive implementation. Future directions may include rigorous validation, practical implementation models, and digitally enabled monitoring tailored to diverse Asian healthcare systems. Although definitive disease-modifying effects remain unproven, integrated lifestyle medicine may offer a practical foundation for translating accumulating lifestyle evidence into more rigorous and scalable neuroprotective strategies for PD.

Previous studies have observed a correlation between plasma gelatinase-associated lipocalin (NGAL) levels and cognitive function in drug-naïve patients with schizophrenia (DNS), but the mechanism is unclear. Basic research suggests that the neuroprotective effect of NGAL may be related to the regulation of growth factors. So, we hypothesized that growth factors such as brain-derived neurotrophic factor (BDNF) mediated the effect between NGAL and cognitive function in DNS. This study recruited 137 DNS patients and divided the patients into severe cognitive impairment group (SCI-DNS, n = 58) and non-SCI group (non-SCI-DNS, n = 79) according to the MATRICS Consensus Cognitive Battery (MCCB), with SCI defined as MCCB composite T-score < 25. Sociodemographic characteristics, cognitive function, psychotic symptoms and peripheral blood samples were collected from all participants. Plasma levels of NGAL, BDNF, epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) were measured using enzyme-linked immunosorbent assay (ELISA). (1) SCI was observed in 42.3% of DNS. (2) Plasma levels of NGAL, BDNF, and EGF were significantly lower in the SCI-DNS group compared with the non-SCI-DNS group. (3) Plasma NGAL exhibited significant positive correlations with all three growth factors (BDNF, EGF, VEGF). (4) Plasma NGAL, BDNF, and EGF levels were positively associated with cognitive function. (5) Plasma BDNF demonstrated a significant mediating effect in the relationship between plasma NGAL and cognitive function. In patients with DNS, those with SCI exhibited lower plasma levels of NGAL, BDNF and EGF. Notably, a significant BDNF-mediated pathway was identified in the association between NGAL and cognitive function.

Patients with Parkinson's disease now live for decades after deep brain stimulation, and many develop recurrent symptoms while the stimulator still functions. A continuous infusion is sometimes added, but the circumstances justifying it are undefined, and the two modalities are still viewed as competing rather than complementary. This review examines the addition of the four infusion therapies after stimulation. A search of three databases identified fifteen reports, almost all small and retrospective. They report 118 patients and 119 infusion courses: 68 with intestinal levodopa gel, 23 with apomorphine, 28 with foslevodopa/foscarbidopa, and none with entacapone. Off time fell in every study that measured it, though fewer than half did. The on-state motor examination improved significantly only in the largest series to test it. In a post hoc trial subgroup, off time improved similarly with and without previous stimulation, while activities of daily living and speech improved significantly less in those with prior stimulation. Severe adverse events were more frequent after prior stimulation. The combination is uncommon: 1% to 2% of patients in larger cohorts, under 0.1% in a national apomorphine cohort. Stimulation parameters are reported or unchanged in only 10 of the 118 patients, and primary failure cannot be separated from secondary failure in 29. We propose a structured assessment separating correctable device problems, recurrent dopaminergic symptoms, stimulation-induced effects and levodopa-resistant progression. Infusion therapy may help recurrent levodopa-responsive complications after stimulation has been re-evaluated and optimized. Its use in late axial or cognitive decline is untested rather than disproven.