This report details a case of a patient in his 60s who exhibited ataxic gait, frequent falls, limb incoordination, tremors and rigidity, leading to a diagnosis of progressive supranuclear palsy with cerebellar predominance (PSP-C). Clinical assessment indicated slurred speech, increased muscle tone, deep tendon reflexes that were mildly reduced asymmetrically on the left side and reduced strength, while sensations remained intact. PSP-C is an uncommon variant of PSP often misidentified as multiple system atrophy-cerebellar type (MSA-C) because of shared characteristics. The patient participated in a comprehensive physiotherapy programme that included transfer training and promotion of independence in activities of daily living while also targeting rigidity and tremors. This case illustrates the diagnostic difficulties associated with addressing motor impairments, fall prevention and improving quality of life in a condition with few treatment alternatives.

Safinamide is a selective, reversible monoamine oxidase type B inhibitor (MAO-B inhibitor) used as an adjunct to oral levodopa in patients with Parkinson's disease (PD) experiencing motor fluctuations. Unlike other MAO-B inhibitors, safinamide possesses a dual mechanism of action, combining dopaminergic enhancement through MAO-B inhibition with modulation of abnormal glutamatergic transmission. In clinical practice, safinamide is primarily recognized for its ability to reduce motor fluctuations. However, its pharmacological profile suggests a broader therapeutic potential beyond dopaminergic modulation alone. Randomized controlled trials have shown that safinamide increases daily ON time without worsening troublesome dyskinesia. Nevertheless, reported effects on dyskinesia have generally been modest and inconsistent across studies. Clinical observations from longer-term follow-up and real-world studies suggest that improvements in dyskinesia and certain non-motor symptoms may emerge more gradually than the early motor benefits. Based on this observed pattern, it can be hypothesized that safinamide may exhibit a dual timeline of clinical effects, with early dopaminergic improvements in motor ON time followed by later modulation of dyskinesia and selected non-motor symptoms potentially mediated through glutamatergic mechanisms. On the basis of these pharmacological characteristics and clinical observations, a phenotype-oriented approach to patient selection for safinamide therapy may be considered. In addition, recognizing the potential for a dual timeline of therapeutic effects may help clinicians guide patients' expectations of treatment and interpret treatment response, as well as optimizing follow-up strategies in routine clinical practice.

Parkinson's disease (PD) ranks second among prevalent global neurodegenerative disorders. It is pathologically characterized by gradual degeneration of midbrain substantia nigra compacta dopaminergic neurons and excessive α-synuclein (α-syn) accumulation forming Lewy bodies. Clinically, patients suffer from motor dysfunctions including resting tremor and muscle stiffness, accompanied by cognitive decline and other non-motor complications, which greatly impair daily life, and there is still no definitive cure. Both genetic predisposition and environmental stimuli jointly drive PD onset. Fine particulate matter PM2.5, a major environmental hazard, carries lipophilic quinone substances capable of crossing the blood-brain barrier and inducing central nervous system injuries. Certain polycyclic aromatic hydrocarbon (PAH) congeners in PM2.5 are highly toxic and produce abundant reactive oxygen species (ROS) to disrupt intracellular signal transduction. This review centers on PD pathogenesis induced by well-studied PAHs and experimental PAH mixtures. In vitro cell assays and in vivo animal studies demonstrate that these tested PAHs aggravate neuronal damage via established suppression of the aryl hydrocarbon receptor (AhR)-retinoid-related orphan receptor α (RORα)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling axis and emerging evidence of reduced α-syn O-linked β-N-acetylglucosaminylation (O-GlcNAc) modification. Two mutually crosstalk pathways (partially speculative regulatory models) further trigger oxidative stress, mitochondrial damage, abnormal protein deposition and cell apoptosis. Notably, PAHs represent a large and structurally diverse family; the summarized mechanisms are validated based on limited PAH species with distinct toxicity, bioavailability and environmental abundance, and cannot be generalized to all PAH congeners. further triggering oxidative stress, mitochondrial damage, abnormal protein deposition and cell apoptosis. The paper also clarifies the crosstalk and positive feedback between the two pathways, summarizes targeted therapeutic strategies and research prospects, aiming to lay theoretical and experimental foundations for exploring environmental pollutant-related PD etiology, prevention and clinical treatment.

The decoding of latent neural states from observable signals is a key focus of modern brain-AI research. Although most neural decoding models are based on electrophysiological recordings, peripheral motor outputs also convey information about circuit-level dynamics. Handwriting is a channeled behavioral signal that indexes the health of the cortico-basal ganglia-thalamo-cortical loop. In Parkinson's disease (PD), dopaminergic loss disrupts this circuit, leading to tremor oscillations, micrographia, and movement irregularities. The challenge of decoding behavior-encoded neural signals from handwriting images constitutes a principled neural signal interpretation problem. We propose a physics-informed and interpretable AI framework for decoding basal ganglia motor dysfunction through harmonic oscillator perturbation analysis. Six energy-inspired measures are extracted to quantify different aspects of motor system dynamics: intensity variation, spatial gradients, multi-scale stability, deviation variability, directional anisotropy, and cross-scale interactions. The transparent mapping between computational models and neurophysiological processes is enabled by these steps, which have their basis in mechanistic theories of amplitude modulation and oscillatory instability. High levels of discrimination were achieved when 594 handwriting trials (279 with PD and 315 controls) were assessed using repeated 10-fold cross-validation for spiral, circle, and meander tasks. Support Vector Machines achieved 84.06% accuracy and 93.56% sensitivity, with highly significant group differences across all features (p < 10-33; Cohen's |d| = 0.87-1.51). Through the integration of physics-based modeling and interpretable machine learning, the proposed framework extends neural signal interpretation beyond direct neural recordings, establishing handwriting as a low-cost, behaviorally encoded biomarker of circuit state and advancing AI-driven decoding of brain dysfunction.

Parkinson's disease (PD) is the fastest growing progressive neurological disorder globally, characterized by motor symptoms such as bradykinesia, rigidity, resting tremor as well as a wide range of non-motor manifestations. Here, we report the case of a patient with advanced Parkinson's disease diagnosed for PD more than 12 years ago; clinical symptoms included a coarse resting tremor with a focus on the right arm and leg, gait and postural disturbances, sleep disorders and autonomic disfunctions. The patient received several medications for correction of dopamine deficiency, but clinical symptoms progressed over the years. We applied a series of double-filtration apheresis treatments and experienced marked symptomatic improvement, with near-complete resolution of motor deficits and strong decrease of MDS-UPDRS part III score. This case suggests a potential role of extracorporeal blood purification in the management of PD.

Manganese (Mn) toxicity is a relatively uncommon neurotoxic condition characterized by neuropsychiatric symptoms and parkinsonism. We describe a 46-year-old woman with end-stage renal disease due to congenital obstructive uropathy, status post deceased-donor kidney transplantation (2021), who presented with one month of worsening tremors, gait instability, intermittent aphasia, and altered awareness. Brain magnetic resonance imaging demonstrated persistent but improved T1 hyperintensity of the globus pallidus compared to prior imaging, consistent with Mn deposition. Serum Mn was markedly elevated at 14.9 µg/L (reference range 0.5-1.2 µg/L). Chelation therapy with calcium disodium ethylenediaminetetraacetic acid was initiated but discontinued early due to decline in renal function. Despite early cessation, treatment resulted in biochemical improvement and partial clinical recovery. Kidney allograft biopsy, performed due to a rise in creatinine during the hospital course, demonstrated severe chronic changes without evidence of acute rejection. Thorough history taking and evaluation of environmental factors did not identify a clear source of Mn exposure. The patient's history was notable for Budd-Chiari syndrome with portal hypertension status post transjugular intrahepatic portosystemic shunt, which likely contributed to impaired Mn clearance. To our knowledge, Mn toxicity occurring in a functioning kidney transplant recipient has not previously been reported. This case underscores the diagnostic and therapeutic challenges of Mn toxicity.