ABSTRACT Prodromal symptoms of psychosis are a public health problem that causes distress and are linked to schizophrenia. However, knowledge among school students from the community is limited. The study aimed to know the relationship of prodromal symptoms of psychosis with suicidal ideation in school adolescents from a city in the Caribbean Region of Colombia. A cross-sectional study was conducted, with participants being tenth- and eleventh-grade students. The participants filled out the prodromal symptoms questionnaire (PQ-16) and an item that assessed suicidal ideation in the last year. Odds ratios (OR) with 95% confidence intervals (95% CI), crude and adjusted, were calculated. The study included 334 participants aged 13–17 years (M = 15.19, SD = 1.10); 51.29% were women. The percentages of affirmative responses for the items of the PQ-16 were observed between 21.26% and 60.18%, and that of suicidal ideation was 28.74%. Suicidal ideation was associated with some prodromal symptoms of psychosis, particularly auditory hallucinations (OR = 3.48, 95% CI 2.81–11.05), avolition (OR = 3.29, 95% CI 1.63–6.66), paranoia (OR = 2.93, 95% CI 1.52–5.65), perceptual abnormalities (OR = 2. 87, 95% CI 1.30–6.32) and excessive social anxiety (OR = 2.43, 95% CI 1.24–4.72). In conclusion, there is a significant association between auditory hallucinations, paranoia, perceptual abnormalities, avolition, excessive social anxiety and the presence of suicidal ideation during the most recent year. Future studies should consider more representative samples and longitudinal designs.

Prodromal symptoms of sporadic amyotrophic lateral sclerosis (SALS) including muscle cramps were reported; however, their detailed characteristics have not been sufficiently studied. To clarify the detailed profiles of prodromal symptoms in SALS. Patients with SALS (n = 47) and healthy controls (n = 25) were enrolled. A questionnaire-based survey was conducted to investigate symptoms before and after disease onset, including sensory, autonomic, sleep, cognitive disturbances, and frequent muscle cramps. Frequent muscle cramps were defined as those occurring at least twice per month in the lower limbs, or at least once per month in the upper limbs or trunk. We evaluated the relationship between surveyed symptoms and clinical characteristics. Prodromal frequent muscle cramps were observed in 29.8% of SALS patients, most frequently in the lower limbs. With disease progression, the sites with cramps increased, and the frequency of cramps during awakening also increased. The SALS patients with prodromal cramps had greater lean mass than those without (p = 0.023). Multivariate analysis showed that the presence of cramps after disease onset was associated with a slower longitudinal decline in the ALSFRS-R score (p = 0.048). Upper limb-onset SALS patients experienced cramps more frequently before onset than bulbar-onset patients did (p = 0.033). Frequent muscle cramps often precede muscle weakness during the prodromal phase of limb-onset SALS. The frequency of cramps increased with disease progression. Prodromal cramps were associated with lean mass, whereas cramps after disease onset were associated with a slower rate of disease progression.

Alzheimer's disease (AD) develops gradually, with significant neurodegeneration already present by the time clinical symptoms emerge. Since synapses are affected early in the disease, synaptic proteins are being investigated as potential markers of the prodromal stage. Using data and plasma samples provided by the Consortium for the early identification of Alzheimer's disease-Quebec (CIMA-Q), we analyzed plasma levels of neuroligin (NLGN)-derived peptides in cognitively normal (CN) individuals and cognitively impaired (CI) individuals, including those with amnestic mild cognitive impairment (aMCI) and early-stage Alzheimer's disease (AD). Plasma levels of NLGN-derived peptides were assessed by quantifying tryptic peptides using liquid chromatography coupled with tandem mass spectrometry. Our findings show that levels of specific NLGN peptides were significantly elevated in CI compared to CN individuals. Receiver operating characteristic (ROC) curve analysis revealed that some NLGN peptides could distinguish CI individuals. Furthermore, analysis based on Mini-Mental State Examination (MMSE) scores revealed that specific plasma phosphorylated tau peptides were significantly and positively correlated with selected NLGN-derived peptides in more advanced stages of cognitive decline. These results support further investigation into synaptic NLGN-derived peptides in the blood as promising tools for monitoring the earliest stages of AD.

Early and accurate diagnosis of mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease (AD), is critical for timely intervention and management. Nevertheless, effectively integrating heterogeneous multi-modal data for AD diagnosis remains worthy of further investigation. Therefore, we propose a supervised contrastive learning framework that integrates single nucleotide polymorphisms (SNPs), plasma proteomics, and T1-weighted structural magnetic resonance imaging (sMRI) from a biologically informed perspective, with SNPs influencing protein structure or gene expression levels, ultimately altering brain structure. Through a supervised contrastive learning mechanism, we construct a cross-modal feature space and introduce a similarity-based symmetrical attention mechanism to capture intermodal interactions and mitigate modality heterogeneity. We validate the proposed method on the Alzheimer's Disease Neuroimaging Initiative dataset, and experimental results demonstrate accuracy of 96.1%, 86.2%, and 86.1% for the AD-NC task, MCI-NC task, and AD-MCI task. In addition, the application of explainable methods to our model identified multi-modal biomarkers related to AD diagnosis. The experimental results validate the effectiveness of our model in the diagnosis of AD and MCI.

Evaluating prodromal symptoms and health locus of control as predictors of seizure reactivity and neuropsychiatric outcomes in drug-resistant epilepsy: a cross-sectional study.

Dual glymphatic roles in first-episode schizophrenia and clinical high-risk for psychosis: Evidence from diffusion tensor image analysis along the perivascular space index.

Charcot–Marie–Tooth (CMT) disease represents the most prevalent inherited peripheral neuropathy with a broad range of clinical manifestations, inheritance patterns, and causative genes. The primary pathological hallmark is progressive degeneration, predominantly affecting sensory and motor neurons, leading to prominent sensory deficits and progressive motor impairments. While neuropathy-causing mutations in the ubiquitously expressed small heat shock protein HSPB1 account for a subset of axonal CMT cases, the mechanisms underlying the selective vulnerability of peripheral neurons remain poorly understood. In this review, we synthesize emerging evidence to reframe HSPB1-related CMT as a prototypical gene–environment interaction disorder. The unique anatomical exposure and high metabolic demands of the peripheral nervous system (PNS) render it particularly vulnerable to HSPB1 mutation-mediated homeostatic collapse, which manifests through three interconnected pathological axes: proteostatic disturbance, cytoskeletal dysregulation, and mitochondrial dysfunction. Crucially, these deficits converge to impair the stress adaptability of peripheral neurons, creating a maladaptive feedback loop wherein environmental stressors exacerbate intrinsic vulnerabilities. We further propose a phase-specific therapeutic framework that prioritizes early intervention during the clinically silent yet biologically active prodromal stage, when targeted modulation of the HSPB1 chaperone interactome and remodeling neural homeostasis may forestall neurodegeneration. This therapeutic paradigm shift from symptomatic management to preclinical neuroprotection underscores the imperative for precision medicine approaches in future CMT intervention.

Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson's disease (PD). However, no study has investigated peripheral BDNF levels and BDNF Val66Met polymorphism in the prodromal stage of PD and their relationship with disease conversion. 120 patients with video-polysomnographically (v-PSG) confirmed iRBD and 120 healthy controls (HCs) were enrolled. Genetic analyses were performed, and plasma levels of BDNF were measured. All patients with iRBD underwent comprehensive clinical testings, and 107 iRBD patients were prospectively followed-up. Plasma BDNF levels were significantly lower in the iRBD group than in HCs (18878.85 pg/ml vs. 24649.85 pg/ml, p = 0.002), but no differences were observed in BDNF Val66Met carrier rates between the two groups. Plasma BDNF levels did not differ significantly between BDNF Val66Met carriers and non-carriers. Notably, higher plasma BDNF levels were associated with an increased risk of short-term disease con-version (Hazard Ratio = 3.418, 95% CI 1.520-7.684, p = 0.003), whereas BDNF Val66Met carrier rates showed no such association. Our findings suggest that plasma BDNF is significantly associated with iRBD and may likely serve as a prognostic biomarker for the development of neurodegenerative dis-ease. However, the BDNF Val66Met polymorphism may not be involved in the path-ogenesis of iRBD as well as phenoconversion in the studied population.

Background:Although hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are inherited disorders expected to display a 1:1 sex ratio, most studies report a strong female dominance. This study analyzed sex differences in 122 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD using the 2017 criteria.Methods:Self-reported data was obtained from November 1, 2019, to April 25, 2025, (n=2,451) from an Intake Questionnaire of adult (≤18 years old) patients diagnosed with hEDS or HSD at the EDS Clinic at Mayo Clinic Florida and analyzed by sex.Results:We found that 90.6% (n=575) of hEDS patients were female and 9.4% (n=60) were male, with a sex ratio of 9.6:1 female-to-male, while 95.2% (n=1,728) of HSD patients were female and 4.8% (n=88) were male, with a sex ratio of 19.6:1 female-to-male. Females were older than males: hEDS 35 vs. 28 years of age (p<0.001), HSD 34 vs. 31 years of age (p=0.004). Overall, females self-reported more symptoms/comorbidities than males: hEDS 31/122 (25.4%), HSD 59/122 (48.4%). In contrast, only 5/122 (4.1%) symptoms/comorbidities were self-reported more often in males including attention deficit disorder/attention deficit hyperactivity disorder, delay in developmental milestones, snoring, autism spectrum disorder, and obstructive sleep apnea. Females with HSD had more mast cell-related symptoms (i.e., hivesp<0.001) which were reflected in higher mast cell scores than males (p<0.001). Patients with higher mast cell scores also had higher serum levels of total IgE (p=0.029). More females with HSD were diagnosed with fibromyalgia (p<0.001) and reported symptoms associated with autonomic dysfunction than males. Aside from abuse, which was higher in females (hEDSp=0.039, HSDp<0.001), few sex differences were reported for psychological symptoms/comorbidities. In support for the idea that elevated mast cell activity in females may lead to extracellular matrix remodeling that promotes hypermobility, females with hEDS/HSD had greater serum collagen-4α1 (p<0.0001) and fibronectin (p=0.015) than males by ELISA.Conclusions:Females with hEDS and HSD report a higher burden of symptoms/comorbidities than males, providing a possible explanation for fewer males being reported in demographic data. Sex differences in symptoms/comorbidities may reflect sex differences in pathogenic drivers of disease.

Brain cholinergic imaging in isolated REM sleep behavior disorder: Distinctions and similarities with Parkinson's disease.

Objective: This study aimed to investigate the prevalence of apathy in Parkinson’s Disease (PD) and explore its potential clinical correlates. Methods: Ninety-eight patients diagnosed with PD based on MDS clinical criteria and followed at the Movement Disorders Clinic of Sakarya University were included. Apathy was assessed using the Starkstein Apathy Scale. Clinical features including disease stage, motor subtype, prodromal symptoms, and daily total levodopa dosage were evaluated in relation to apathy status. Results: Apathy was detected in 59.2% of the participants. The apathy-positive group had significantly higher UPDRS III and H&amp;amp;Y scores (p&amp;lt;0.05), as well as longer disease duration and higher daily levodopa dosages. Although apathy was more frequent in advanced-stage patients and in the akinetic-rigid subtype, these differences did not reach statistical significance. Constipation and REM sleep behavior disorder were more commonly observed in the apathy group, though again without statistical significance. Conclusion: Apathy is a common and clinically relevant non-motor symptom in PD, particularly associated with greater motor impairment and longer disease duration. Our findings underline the need for increased awareness and further investigation into the pathophysiology and clinical management of apathy in PD.

Progranulin is increased during prodromal pathology in LRRK2 G2019S mice.

Research progress on the prodromal symptoms of cardiac arrest

Objective: Syncope, a temporary loss of consciousness caused by cerebral hypoperfusion, is often benign but can signal serious neurological or cardiac issues. We retrospectively analyzed pediatric syncope cases in this study. Material and Methods: We analyzed 514 patients aged 6–18 years who presented with syncope to a pediatric neurology outpatient clinic. Results: Most patients (36.7%) had a single episode, though recurrent cases were also common. The primary triggers were prolonged standing (17.2%) and sudden postural changes (14.4%). Prodromal symptoms such as dizziness, visual disturbances, and nausea were reported in 69.5% of cases. Electroencephalography (EEG) was performed in 72.2% of patients, revealing epileptiform activity in 27 individuals. EEG requests increased significantly in patients with recurrent syncope episodes (p&lt;0.010). Cranial MRI was performed in 37.5% of the patients, and abnormalities were detected in 16.6%, most commonly arachnoid cysts. However, no statistically significant correlation was found between MRI utilization and the frequency of syncope episodes. Final diagnoses were predominantly vasovagal syncope (75.6%), followed by psychogenic syncope (10.3%), seizures (8.75%), cardiogenic syncope (4.5%), and hypoglycemia (0.85%). Conclusion: These results highlight the mostly benign nature of pediatric syncope, with vasovagal syncope as the most frequent diagnosis. EEG is useful for identifying underlying epilepsy, while neuroimaging should be reserved for selected cases.

In Ayurveda the word Udar (abdomen) is used in a broad sense, abdomen includes organs like liver, spleen, stomach, intestines etc. abdominal diseases is considered to be under Astamahagad (eight major diseases) hence the treatment of abdominal disease is difficult. In the modern era, due to wrong eating habits and busy lifestyles, like kidney and heart disorders, liver disorders (Yakritroga) have also started affecting life. By studying the Panchnidan which comprises of five aspects such as Nidan (Etiology of the disease), Purvroop (Prodromal symptoms), Roop (Symptoms), Upshay (Palliative care) and Samprapti (Pathogenesis), help us to understand the disease completely. According to Ayurveda in the line of treatment of any disease “Nidanparivarjan” (avoid disease causing factors) is considered the first step of treatment, this breaks the spread of disease and prevent it from progressing to the advanced stage.

Due to the late manifestation of structural symptoms and symptomatic overlap, neurodegenerative diseases such as Parkinson's Disease (PD) and Alzheimer's Disease (AD) remain difficult to diagnose accurately. In order to categorize AD and PD in comparison to Healthy Controls (HC), this study suggests a multimodal classification framework that combines genetic Single Nucleotide Polymorphism (SNP) data, structural Magnetic Resonance Imaging (MRI), and functional Electroencephalography (EEG). To improve the model's accuracy and interpretability, the method makes use of an uncertainty estimate module and a novel cross-modality attention mechanism. The framework strives for diagnosis, concentrating on detecting Parkinson's disease (PD) and Alzheimer's disease (AD) in individuals exhibiting modest motor symptoms or early cognitive impairments, which are indicative of the prodromal stage of both conditions. A dataset of 2,500 MRI images, 1,500 EEG recordings, and SNP data for 1,000 subjects drawn from OpenNeuro, PPMI, and the UK Biobank was utilized in extensive analyses. The developed model was contrasted with recent unimodal and multimodal techniques. Our findings exhibit statistically significant increases of 6-12% compared to similar methods, with 95.6% average classification accuracy on AD and 94.8% on PD. The importance of the attention mechanism and both modalities to overall performance is quantified using ablation studies. Quantification of uncertainty also improves interpretability for possible clinical use. These results demonstrate the proper neurodegenerative disease diagnosis when explainable AI elements are paired with stable multimodal fusion.

Alterations in gray matter volume and cortical thickness in medication-naive offspring with ADHD and a parental history of bipolar disorder.

PROK2 is a peptide expressed in the adult brain mediating neuroprotective functions. Previous studies reported an upregulation of prokineticin system in PD, but evidence in prodromal α-synucleinopathies was lacking. We investigated the expression of prokineticin-2 (PROK2) and its receptors (PKR1 and PKR2), along with oligomeric α-synuclein (oligo α-syn) as a marker of α-synuclein pathology, in olfactory neurons (ONs) from individuals with idiopathic REM sleep behavior disorder (iRBD). ONs, obtained by nasal brush from 28 iRBD subjects (age:71.2±7.4years; males:89.3%; duration:4.9±2.5years) and 28 healthy controls (HCs) (age:67.2±11.5years; males:64.2%), were analyzed using real-time polymerase-chain-reaction (RT-PCR), immunofluorescence (IF), and western blot (WB). In a subgroup of subjects, results were validated in serum. In the iRBD group, PROK2 protein expression was reduced in both ONs (IF: F(1,26) = 15.289, p<.001; WB: F(1,12) = 9.073, p=.011) and serum compared with HCs (WB: F(1,12) = 4.557, p=.050). iRBD subjects showed lower mRNA expression of prokineticin receptors compared with HCs (RT-PCR for PKR1: F(1,26) = 16.131, p<.001; RT-PCR for PKR2: F(1,39) = 4.946, p=.032). Oligo α-syn accumulation in ONs was higher in iRBD than HCs, yet the difference only tended to statistical significance (IF: F(1,18) = 3.169, p=.092). In contrast with findings in PD, we found a downregulation of prokineticin system in iRBD. The causes of prokineticin system downregulation in this prodromal stage may be multiple. The absence of clear oligo α-syn accumulation, known trigger of PROK2, may play a role. On the other hand, a lack of activation of this system might act as predisposing factor for the development of iRBD and, subsequently, full-blown neurodegeneration.

Autonomic dysfunction is a known contributor to cognitive impairment in Parkinson's disease (PD), but its impact during prodromal stage is unknown. The aim was to determine whether early autonomic burden predicts incident cognitive impairment in prodromal PD. We analyzed data from Parkinson's Progression Markers Initiative participants. Autonomic dysfunction was defined as Scales for Outcomes in Parkinson's Disease Autonomic Dysfunction score ≥13, documented prior to phenoconversion. Cox regression assessed the predictors of cognitive impairment, and mixed-effects analysis of variance compared domain-specific cognitive trajectories. Data on 382 participants were analyzed. Early autonomic dysfunction was significantly associated with increased risk of mild cognitive impairment or dementia (P < 0.001), especially in semantic fluency and letter-number sequencing. Cardiovascular autonomic burden, specifically, was a strong independent predictor (HR = 5.21, P = 0.01). Autonomic dysfunction in prodromal PD is a risk factor for cognitive decline, providing opportunity for early risk stratification and intervention. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Early detection of Mild Cognitive Impairment (MCI), a prodromal stage of dementia, plays a pivotal role in enabling timely clinical intervention and slowing cognitive decline. This paper presents a multi-sensor balance assessment framework designed to identify MCI-related postural instabilities using a wearable inertial measurement unit (IMU) network. The proposed system employs five synchronized IMUs placed at the waist, thighs, and shanks to capture balance dynamics across four static balance tasks: Eyes-Open, Eyes-Closed, Right-Leg Lift, and Left-Leg Lift. A three-stage feature selection strategy, comprising variance and correlation pruning, univariate filtering, and embedded model selection, is implemented within a Leave-One-Subject-Out (LOSO) cross-validation scheme to extract discriminative sway features. Classification using Support Vector Machines and tree-based ensemble models consistently yields superior results, achieving accuracies between 71.7% and 79.2%, with the highest performance observed in the Eyes-Open condition. A compact 10-feature subset demonstrates stable and robust discriminative power across all tasks. Compared to a single-sensor baseline, the multi-sensor configuration provides improved classification performance, underscoring the feasibility of compact, balance-driven, non-invasive MCI screening through wearable sensor systems.