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PubMed2026

Non-motor symptoms and healthcare utilization before diagnosis of myasthenia gravis: a nationwide cohort study.

BACKGROUND: Non-motor symptoms have been reported prior to myasthenia gravis (MG) diagnosis. However, the temporal patterns of non-motor symptoms and healthcare utilization before MG diagnosis remain unclear. METHODS: We conducted a retrospective, population-based cohort study using the Korean National Health Insurance Service (KNHIS) database from 2011 to 2021. Incident MG cases were identified using the International Classification of Diseases, Tenth and Rare Intractable Disease codes. Individuals younger than 20  years or with missing health screening data were excluded. Each MG case was matched 1:10 by age, sex, and index date to controls. Non-motor symptoms and healthcare utilization were defined using operational criteria derived from KNHIS claims data. Rate ratios (RRs) and 95 % confidence intervals (CIs) were estimated across four prespecified intervals (0-1, 1-2, 2-5, and 5-10  years) before MG diagnosis. RESULTS: We included 8,355 MG patients and 83,550 controls (mean age, 53.7  years; male, 44 %). MG patients had higher rates of any non-motor symptoms over 10  years(RR 1.34; 95 % CI 1.30-1.39), with the sharpest increase in the year before diagnosis. Depression, anxiety, migraine, constipation, and insomnia consistently showed higher RRs across all intervals. Hospitalizations (RR 1.66; 95 % CI 1.61-1.71) and outpatient clinic visits (RR 1.10; 95 % CI 1.04-1.17) were consistently higher across 10  years, peaking during the 0-1 year before MG diagnosis. CONCLUSION: Non-motor symptoms and healthcare utilization increased years before MG diagnosis. Earlier recognition of these symptom patterns may facilitate timelier evaluation for MG and improve diagnostic pathways.

Humans↗

PubMed1979

[Strabismus in cerebral paretic and normal children. Comparison of motoric symptoms (author's transl)].

Investigations of 94 children with cerebral palsies have shown 55% strabismus incidence. Motoric symptoms like varying angles, nystagmus (latens), A-V phenomena, dissociated hypertropia and compulsive head postures are presented, frequently more often than in a number of comparison cases of undamaged squinting children. However, these symptoms have not permanently been found even in severly damaged children. With the exception of compulsive head postures, no symptoms are found in strabismus cases of cerebral paretic children that do not occur in congenital strabismus patients as well. A frequent family heredity strain of strabismus has also been noted. There is a striking proportion of divergence cases (27%). The authors do not believe in a simple damaging etiology. Pleoptic-orthoptic exercises are hardly ever practicable. Early operation may improve the initial situation as far as the neuropediatric therapy is concerned.

Adolescent↗

PubMed1978

[Course of psychopathologic and extrapyramidal motor symptoms during long-term treatment of schizophrenic patients with psycholeptic drugs (author's transl)].

65 chronic-schizophrenic outpatients were treated with fluphenazinedecanoate for 24 months. Hallucinations and delusions remitted between week 24 and 36, formal disturbances of thinking occurred in 50% of the patients up to the 24th week, mood disorders and disorders and schizophrenic changes in personality could only gradually be controlled. In the first 3 months of treatment the incidence and intensity of rigor grew up to the critical point after 24 weeks of treatment; by the 60th week of treatment it had completely vanished. Akathisia reached its peak after the first and the 36th week and two different populations could be distinguished. 8% of the patients showed dyskinetic reactions up to the 12th week; 20% of the patients showed hyper- and dyskinesia after 72 weeks of treatment. 30 to 40% of the patients required anticholinergics between the 12th and 48th weeks; after the 84th week this medication was no longer necessary.

Adolescent↗

PubMed1978

[Proskinetic symptoms in motor psychosis as accentuating personality traits].

Proskenetic symptoms have been observed by the authors in a study of motility psychosis. However, these proskinetic symptoms appeared to be a character trait of an infantile personality rather than a condition following as a consequence of psychosis. The question is raised as to whether proskinetic symptoms (and catatonic symptoms) may be considered accentuating personality traits.

Adult↗

PubMed2026

A systematic review and meta-analysis of visuospatial attentional deficits in Parkinson's patients.

Parkinson's disease (PD) is a neurodegenerative condition primarily characterized by motor deficits, yet cognitive impairments are increasingly recognized. While deficits in executive functioning are well documented even in the absence of cognitive decline, evidence of attentional deficits in PD remains inconsistent, and the role of motor symptom lateralization is unclear. In this systematic review and meta-analysis, we examined visual attention in right-handed, cognitively unimpaired idiopathic PD patients, focusing on the canonical attentional domains (sustained, selective, divided) and processes (alerting, endogenous and exogenous orienting, reorienting), as well as visuospatial bias. Four databases were searched for studies comparing PD patients with healthy controls. Meta-analytic estimates were derived using Hedges' g within random-effects models, and studies that could not be quantitatively integrated were summarized narratively. In addition, studies directly comparing patients with left- and right-predominant motor symptoms (LPD vs. RPD) were reviewed qualitatively. Across 51 studies, PD patients exhibited deficits in sustained, selective, and divided attention. Among attentional processes, only exogenous orienting was impaired, whereas alerting, endogenous orienting, and reorienting were preserved. Findings from the few studies examining visuospatial bias indicated small, context-dependent shifts in spatial attention rather than a consistent directional bias. These findings indicate that PD patients show visual-attentional impairments, particularly under high-demand conditions, while basic alertness and voluntary orienting appear preserved. Exogenous orienting deficits and subtle rightward spatial tendencies in LPD suggest disruption of right-hemisphere attentional networks. These results have implications for early cognitive assessment, rehabilitation strategies, and understanding the neural bases of attentional dysfunction in PD.

Humans↗

PubMed2026

Digital profiling of dysarthria in late- and early-onset Parkinson's disease.

BackgroundDigital speech analysis affords robust markers of Parkinson's disease (PD). However, most studies target late-onset PD (LOPD), neglecting early-onset PD (EOPD) -an increasingly prevalent subtype. This proof-of-concept study tackles such gap.MethodsWe used machine learning to discriminate persons with EOPD (with symptom onset before age 50) and LOPD (with symptom onset after age 50) from healthy controls (HCs) through prosodic and articulatory features from natural speech.ResultsMaximal classification between patients and HCs was afforded by combined prosodic and articulation features in LOPD (AUC = 0.90) and by articulation alone in EOPD (AUC = 0.79), with chance-level discrimination between patient groups (AUC = 0.55). Motor severity (MDS-UPDRS-III) scores predicted by these features correlated with actual motor severity scores in both LOPD (r = 0.52, p < 0.001) and EOPD (r = 0.27, p < 0.001).ConclusionsDigital speech markers offer markers of PD irrespective of age of onset.Plain language summary titleVoice recordings capture motor symptoms in Parkinson's disease irrespective of age of onset.

Humans↗

PubMed2026

ACE2 and Parkinsonism‑related bone metabolic alterations: signaling pathways and hub gene analysis.

Clinical co-occurrence of Parkinson's disease (PD) and age-related bone loss in elderly patients has garnered increasing attention, yet its molecular mechanisms remain incompletely elucidated. This study used an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in Ace2-/y mice to investigate the regulatory mechanisms of bone-brain axis-related genes and signaling pathways. Behavioral tests assessed motor and non-motor symptoms. Immunohistochemistry, Western blot, and histopathological staining analyzed dopaminergic neuron activity, microglial activation, and bone metabolic abnormalities. GEO dataset transcriptomics and weighted gene co-expression network analysis (WGCNA) identified key hub genes, with receiver operating characteristic (ROC) curves evaluating their diagnostic value in public single-disease transcriptome data. MPTP significantly exacerbated motor dysfunction and depression-like behaviors; Ace2 deletion lowered total Wnt, β-catenin, BMP and IGF-1 protein abundance alongside reduced phosphorylation ratios of their downstream kinases in brain and bone, while upregulating RANKL/RANK/OPG-associated inflammatory mediators, accompanied by elevated total α-synuclein, Casp3 and Bax protein levels. The parallel reduction of these signaling proteins only suggests potential perturbation of related cascades; WGCNA identified 10 hub genes (e.g., DNM1, OCRL, OPA1), whose dysregulation was linked to synaptic dysfunction and inflammation. ROC analysis based on single-disease datasets showed high diagnostic accuracy for PD and `osteoporosis (OP) (AUC: 0.683-0.981), with core genes influencing synaptic, MAPK, Rap1, and Ras pathways. These preclinical findings indicate that Ace2 deficiency is associated with concurrent pathological abnormalities in the brain and transient bone metabolic disturbance under short-term MPTP treatment in growing young male mice; coordinated dysregulation of shared signaling pathways was observed in the two tissues, consistent with a potential bone-brain axis pathological phenotype, though causal bidirectional tissue cross-talk cannot be confirmed in the current experimental design, providing candidate targets that warrant further validation.

Animals↗

PubMed1979

Postoperative complications in 1,000 cases of intracranial aneurysms.

Clinical analysis of postoperative complications was made in 1,000 cases of intracranial saccular aneurysm. Psychological symptoms, motor disturbances, and aphasia were observed in 107 cases (11.5%), 74 cases (7.1%) and 20 cases (2.1%), respectively, in 939 discharged cases. Water and electrolyte disturbances and gastro-intestinal bleeding were found in 60 cases (6.0%) and 19 cases (1.9%), respectively, in 1,000 surgically treated patients including those that died during hospitalization. Psychological symptoms were most apt to develop in cases of vertebrobasilar artery aneurysm, multiple aneurysms and anterior communicating aneurysm. It appeared that the poorer the preoperative grade, the higher the incidence of psychological symptoms. These developed most frequently in patients operated on the third to seventh days after the subarachnoid hemorrhage. The postoperative psychological symptoms improved in 63% of 107 cases. The occurrence rates of other complications were also studied.

Alcohol Amnestic Disorder↗

PubMed2026

[Clinical efficacy and safety of electroacupuncture at the motor area for Parkinson's disease with musculoskeletal pain: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy and safety of electroacupuncture (EA) at the motor area for Parkinson's disease (PD) with musculoskeletal pain. METHODS: Fifty-eight patients with PD accompanied by musculoskeletal pain were randomly assigned to an EA group (29 cases, 1 case dropped out) and a sham EA group (29 cases, 1 case dropped out). The EA group was treated with EA at the motor area contralateral to the painful side (for bilateral pain, the left motor area was selected), using disperse-dense wave (2 Hz/20 Hz), with a current intensity of 1-2 mA, and needles were retained for 30 min. The sham EA group was treated with sham EA at non-acupoint area located 5-20 mm posterior to the motor area contralateral to the painful side. The connection mode was the same as that in the EA group, but no electrical current was delivered, and the needles were retained for 30 min. Both groups were treated once daily for 5 consecutive days. Visual analogue scale (VAS) for pain, unified Parkinson's disease rating scale part Ⅲ (UPDRS-Ⅲ), 24-item Hamilton depression rating scale (HAMD-24), Hamilton anxiety rating scale (HAMA), and 39-item Parkinson's disease questionnaire (PDQ-39) scores were evaluated before treatment, immediately after treatment, and at 2 and 4 weeks after treatment completion in the two groups. Safety was also assessed in the two groups. RESULTS: In both groups, VAS scores for pain after treatment and at 2 and 4 weeks after treatment completion were lower than those before treatment (P<0.01, P<0.05). VAS scores for pain in the EA group were lower than those in the sham EA group after treatment and at 2 and 4 weeks after treatment completion (P<0.05). In the EA group, UPDRS-Ⅲ, HAMD-24, HAMA, and PDQ-39 scores after treatment and at 2 and 4 weeks after treatment completion were lower than those before treatment (P<0.05, P<0.01). In the sham EA group, there were no statistically significant differences in UPDRS-Ⅲ, HAMD-24, HAMA, and PDQ-39 scores at any post-treatment time point compared with those before treatment (P>0.05). There were no statistically significant differences in UPDRS-Ⅲ, HAMD-24, HAMA, and PDQ-39 scores between the two groups at any post-treatment time point (P>0.05). No serious adverse events occurred during the trial. CONCLUSION: EA at the motor area could reduce pain intensity in patients with PD accompanied by musculoskeletal pain, and improve pain-related motor symptoms, emotional status, and quality of life, with a favorable safety profile.

Humans↗

PubMed2026

Efficacy of citicoline as an add-on therapy in Parkinson's disease: a randomized, double-blind trial.

BACKGROUND: Citicoline is a promising therapeutic option for improving both motor and non-motor symptoms in Parkinson's disease (PD) beyond levodopa and other standard dopaminergic treatments. OBJECTIVES: The CITIPARK study evaluated the efficacy and safety of citicoline in improving clinical outcomes and quality of life (QOL) in PD patients on dopaminergic therapies. METHODS: The randomized, double-blind, multicenter trial compared citicoline (1000 mg/day intramuscular, two six-week cycles) with placebo for 24 weeks in PD under stable medications. The primary endpoint was change in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) total score; secondary endpoints included motor and non-motor subscores, QOL, clinical global impression (CGI) and safety. RESULTS: The study enrolled 485 participants, randomizing 474 (citicoline: 303; placebo: 171). Citicoline significantly increased the likelihood of achieving a minimal clinically important difference compared with placebo (OR 2.06, 95% CI 1.06-3.99; P = 0.031) on the MDS-UDPRS total score in the modified intention-to-treat population. Among secondary outcomes, the citicoline group showed greater improvement in motor function (MDS-UPDRS III -2.97 vs -0.13; p = 0.009) and a greater improvement on CGI -II and CGI-III (3.26 vs 3.59; p = 0.021 and 9.30 vs 10.38; p = 0.018, respectively). AEs occurred in 22.1% and 27.1% of the citicoline and placebo groups, respectively. CONCLUSIONS: Citicoline was well tolerated and associated with motor benefits compared with placebo in a highly compliant population. The results suggest a role of citicoline as a safe and possibly effective supportive therapy in PD treated with concomitant dopaminergic agents.

Humans↗

PubMed1979

Carbamazepine vs phenytoin. A controlled clinical trial in focal motor and generalized epilepsy.

The antiepileptic effects of carbamazepine and phenytoin were compared in a double-blind crossover trial studying patients with primary and secondary generalized seizures and partial seizures with motor symptoms. Each treatment period lasted ten weeks. The patients were seen every two weeks, and doses were adjusted according to plasma levels. It was attempted to keep levels in the optimal plasma range, ie, 10 to 20 and 4 to 10 mg/liter for phenytoin and carbamazepine, respectively. Twenty-three patients entered and 19 completed the study. No statistically significant differences were found between carbamazepine and phenytoin with regard to seizure control and acute side effects.

Adolescent↗

PubMed1976

Neuropsychiatric symptomatology with chronic renal insufficiency in the stage of compensated and decompensated retention. II. Peripheral nerve disturbances.

80 strictly selected patients with chronic renal insufficiency with plasma creatinine values of 1.4-14.5 mg% were examined for clinical and electrophysiological signs of nephrogenic polyneuropathy. The motor symptoms complained of were cramps in 43.8% of the patients, "restless leggs" in 18.7%, muscular twitchings in 12.5%. It was emphasized that the first two symptoms do not always indicate the presence of polyneuropathy. 30% complained of paresthesias, 5% of "burning feet". The most frequent clinical finding was the impairment of vibration sense in the feet in 37.5% followed by diminshed appreciation of passive movement of the toes in 30%, weakening or absence of the ankle jerk in 23.8% and finally, weakening of the patellar reflex in 5%...

Adult↗

PubMed2026

Essence: A benchmarking-validated transformer framework for early diagnosis of Parkinson's disease using cerebrospinal fluid protein biomarkers.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The lack of objective molecular biomarkers limits early diagnosis and personalized treatment. Here, we propose Essence, a benchmarking-validated framework integrating cerebrospinal fluid (CSF) proteomics with traditional and deep learning models to identify robust protein signatures for PD. Using data from two independent cohorts, 1266 high-confidence proteins are quantified, among which 178 exhibit differential abundance between PD and healthy controls (HC). Through systematic benchmarking of ten machine learning algorithms and four neural architectures, the Transformer model consistently outperforms alternatives across multiple feature selection strategies, achieving an area under the receiver operating characteristic curve (AUC) of 1.0000 with only 35 features. Functional analyses of the top-ranked 35 proteins reveal enrichment in neuroinflammatory, synaptic, and oxidative stress-related pathways. Importantly, spatial transcriptomic profiling based on the Allen Brain Atlas shows region-specific expression of these biomarkers in PD-relevant brain structures, including the striatum, subthalamic nucleus, hippocampus, and white matter tracts. This anatomical alignment supports the functional relevance of the identified markers and highlights their potential utility in early-stage diagnosis and mechanistic understanding of PD.

Benchmarking↗

PubMed2025

Parabacteroides goldsteinii mitigates parkinsonism in LRRK2 mutant mice by reducing neuroinflammation through Gut-Brain axis.

INTRODUCTION: Alterations in the gut microbiota accompanied by intestinal inflammation are early features of Parkinson's disease (PD). Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent a common genetic risk factor for PD and inflammatory bowel disease. Parabacteroides goldsteinii has been reported to alleviate intestinal and systemic inflammation. However, whether modulation of the gut microenvironment at early disease stage can attenuate PD progression remains unclear. OBJECTIVE: To investigate the impact of P. goldsteinii colonization prior to the onset of motor dysfunction on PD progression. METHODS: We established a germ-free PD mouse model carrying the LRRK2 G2019S mutation and administered P. goldsteinii orally at the pre-symptomatic stage to evaluate its effects on motor performance and PD-related neuropathology. Spatial and bulk RNA transcriptomic analyses of brain tissue, together with cytokine profiling, were conducted to assess central changes. To investigate gut immunomodulatory mechanisms, we performed intestinal bulk and single-cell RNA sequencing, spectral flow cytometry as well as cellular bioenergetic analyses. RESULTS: Germ-free conditions partially alleviated PD-like phenotypes in LRRK2 G2019S mice. Colonization with P. goldsteinii at 5-months of age, prior to motor symptom onset, further improved locomotor performance, reduced neuronal α-synuclein aggregations, and mitigated microglial activation and dopaminergic neurodegeneration. Neuroprotection was mediated through enhanced noncanonical neuronal IL-12 receptor-dependent neurotrophic support without activating the canonical STAT4 phosphorylation pathway, along with suppression of microglial activation and downregulation of LRRK2 kinase activity. At the intestinal level, P. goldsteinii suppressed TLR4-driven inflammation, expanded anti-inflammatory intraepithelial CD4+CD8αα+ T cells, promoted dendritic cell and macrophage differentiation, upregulated epithelial tight-junction genes, and improved mitochondrial bioenergetics in intestinal cells. CONCLUSION: P. goldsteinii colonization attenuates the progression of LRRK2-associated parkinsonism by restoring intestinal homeostasis and reducing neuroinflammation. These findings underscore the therapeutic potential of modulating the gut-immune-brain axis during the prodromal stage of PD.

Animals↗

PubMed2026

Proteo-metabolomic integration identifies stage-specific candidate biomarkers for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a prolonged prodromal phase and complex motor symptoms. Despite improved clinical criteria, early diagnosis and longitudinal monitoring remain challenging. While cerebrospinal fluid (CSF) and plasma metabolites and proteins show biomarker potential, their utility in predictive models is insufficiently characterized. We employed a secondary computational approach to integrate proteometabolomic profiles from CSF and plasma samples of >1100 Parkinson's Progression Markers Initiative (PPMI) participants. Using multi-omics machine learning, we identified biofluid-specific signatures and evaluated predictive performance. Twenty-one biomarker candidates were validated across three models (SVM, GLMNET, RF); SVM and GLMNET achieved the highest recall (83-86%) and AUCs of 0.84-0.89. Longitudinal mixed-effects modeling revealed eight candidates associated with progression across diagnostic stages. We identified a three-part molecular framework characterizing neurodegeneration: a diagnostic subpanel reflecting early microbiome dysregulation (secretory granins and metabolites) and synaptic breakdown; a second subpanel monitoring phenoconversion via neurogenesis precursors and extracellular matrix proteins; and a third subpanel tracking progression through chronic neuroinflammation and immune activation. This integrated multi-omics approach provides a robust framework for stage-specific PD monitoring and potential clinical deployment.

Journal Article↗

PubMed2025

A blood-based DNA damage signature in patients with Parkinson's disease is associated with disease progression.

Aging is the main risk factor for Parkinson's disease (PD), yet our understanding of how age-related mechanisms contribute to PD pathophysiology remains limited. We conducted a longitudinal analysis of blood samples from the Parkinson's Progression Markers Initiative cohort to investigate DNA damage in PD. Patients with PD exhibited disrupted DNA repair pathways and biased suppression of longer transcripts, indicating age-related, transcription-stalling DNA damage. Notably, at the intake visit, this DNA damage signature was detected only in patients with more severe progression of motor symptoms over 3 years, suggesting its potential as a predictor of disease severity. We validated this signature in independent PD cohorts and confirmed increased DNA damage in peripheral blood cells and dopamine neurons of the substantia nigra pars compacta in postmortem PD brains. Our study sheds light on an aging-related mechanism in PD pathogenesis and identifies potential markers of disease progression, providing a diagnostic platform to prognosticate disease progression.

Humans↗

PubMed2026

Comparison of Proteomic Analysis of Cerebrospinal Fluid From Neurological Patients With and Without Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by progressive muscle weakness in both bulbar and extremity muscles, leading to a diverse clinical phenotype with motor and non-motor symptoms. Approximately 85% of ALS cases are sporadic (sALS), while the remaining 10%-15% are familial (fALS). Biological biomarkers of sporadic ALS remain poorly understood, hindering precise patient screening, delaying diagnosis and negatively affecting prognosis. This study aims to identify potential proteomic biomarkers by comparing the cerebrospinal fluid (CSF) of sALS patients with that of patients suffering from other neurological diseases. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for proteomic profiling of CSF samples from 24 sALS patients and 26 patients with other neurological diseases. The complete protein expression profiles were compared using a two-tailed Student's t-test, with a p < 0.05 considered statistically significant with additional FDR correction at the 0.1 level. Proteomic analysis of CSF samples identified significant quantitative changes in 96 proteins with threshold p < 0.05 and 74 proteins with FDR < 0.1 between sALS and non-ALS patients, including alterations in proteins associated with neurodegenerative processes, such as amyloid precursor proteins and inflammatory markers. CSF proteomic analysis reveals altered inflammatory and neurodegenerative metabolic pathways, providing valuable insights into the proteomic landscape of sALS. Several dysregulated proteins were consistent with the disease mechanisms highlighted in previous studies. These findings represent a step forward in developing personalised approaches for diagnosing and managing the disease.

Humans↗

PubMed2026

One brain, one mind: A joint EPA-EAN leadership perspective on brain health.

Neurology and psychiatry have operated as separate disciplines for over a century, yet this division reflects historical and institutional developments rather than the underlying biology of the brain. Contemporary neuroscience shows that brain and mental health disorders share genetic susceptibilities, inflammatory and metabolic pathways, environmental and social risk factors, and clinical features that cross diagnostic boundaries. Cognitive, emotional, sensory, and motor symptoms regularly appear across both neurological and psychiatric populations, and conditions such as seizures, psychosis, mood disorders, cognitive disorders, and sleep disorders are common to both. A brain health framework addresses this reality by treating the brain as a single biological organ whose function emerges from the interplay between genome and exposome - including stress, trauma, social context, existential meaning, pollution, and physical health - and which underlies perception, behaviour, cognition, emotion, resilience, and vulnerability. Translating this perspective into practice requires coordinated action across domains. Clinically, collaborative models such as joint neurology-psychiatry consultations and shared outpatient pathways can be implemented within existing resources to improve diagnostic clarity and continuity of care. In training, a more harmonised curriculum with shared foundations in neurobiology, joint seminars, and cross-rotations would equip clinicians with a common language while preserving specialist depth, and support the emerging fields of preventive neurology and preventive psychiatry. In research, organising studies around shared mechanisms and symptom dimensions, and launching joint funding calls, would enhance translational relevance and reduce duplication. To realise this vision, sustained leadership from European professional bodies is essential to establish collaboration as a shared professional standard.

Humans↗