BACKGROUND: Current therapies for Parkinson’s disease lack proven disease-modifying effects. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), developed for type 2 diabetes, have shown potential neuroprotective prope...BACKGROUND: Current therapies for Parkinson’s disease lack proven disease-modifying effects. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), developed for type 2 diabetes, have shown potential neuroprotective properties. Their comparative efficacy in Parkinson’s disease remains unclear. METHODS: A systematic search (inception–February 2026) identified randomized controlled trials evaluating GLP-1RAs in Parkinson’s disease. Pairwise and frequentist random-effects network meta-analyses were performed. The primary outcome was MDS-UPDRS Part III (ON state). RESULTS: Five trials (n = 708) were included. Pairwise meta-analysis showed no significant overall improvement in MDS-UPDRS Part III (MD –2.00; 95% CI –5.46 to 1.46; I² = 80.5%). Network meta-analysis demonstrated significant ON-state motor improvement with Exenatide 20 µg/day (MD –9.80; 95% CI –14.47 to –5.13) and Lixisenatide 20 µg/day (MD –3.08; 95% CI –5.31 to –0.85). No significant effects were observed for MDS-UPDRS Part III (OFF-state) or other domains (Parts I, II, and IV; ON-state). NLY01 at 5 mg/week improved PDQ-39, while NMSS showed dose-dependent divergence. Gastrointestinal adverse events were more frequent with GLP-1RAs. CONCLUSION: GLP-1 receptor agonists may provide dose-specific motor benefits in Parkinson’s disease, but evidence for broader clinical improvement is limited. Larger, longer-duration trials are needed.
Piella EM, Chiarandon AM, Albanese M
… +28 more, Puddu EM, Pistoia F, Saporito G, Altieri M, Giuliani G, Vaghi G, Sances G, Munafò A, Chiarugi A, Ornello R, De Santis F, Valente M, Rao R, Russo A, Silvestro M, Roveta F, Montisano DA, Grazzi L, Battistini S, Boscain F, Mampreso E, Paolicelli D, Sacco S, Tassorelli C, Rubino E, Prudenzano MP, Rainero I, Italian Headache Registry (RICe) Study Group
BACKGROUND: The Migraine Interictal Burden Scale (MIBS-4) is a brief validated patient-reported measure of migraine interictal impact; however, an official Italian translation is not currently available. METHODS: The MIB...BACKGROUND: The Migraine Interictal Burden Scale (MIBS-4) is a brief validated patient-reported measure of migraine interictal impact; however, an official Italian translation is not currently available. METHODS: The MIBS-4 was translated and culturally adapted into Italian language and psychometrically evaluated in adults with episodic or chronic migraine enrolled in the Italian Headache Registry (RICe). In a 4-week test–retest design, participants completed the Italian version of MIBS-4 and the Migraine Disability Assessment (MIDAS) at baseline (T0) and at follow up (T1). We assessed internal consistency, dimensionality, test–retest reliability, convergent validity, and known-groups validity across MIDAS disability grades. RESULTS: A total of 191 patients with migraine were included in test–retest analyses. Internal consistency was good to excellent (Cronbach’s α = 0.86 at T0; 0.90 at T1; ordinal α = 0.91–0.94; McDonald’s ω = 0.88–0.91). Parallel analysis supported a stable one-factor solution at both timepoints. Item-level agreement was moderate (weighted κ = 0.45–0.60; all p < 0.001), as was the total-score stability (ICC[A,1] = 0.62, 95% CI 0.50–0.72). Convergent validity with MIDAS was moderate (ρ = 0.40 at T0; ρ = 0.33 at T1; both p < 0.001). DISCUSSION: The present findings indicate that the Italian MIBS-4 is psychometrically robust and captures a dimension of migraine burden that is only partially explained by conventional attack-focused disability measures. CONCLUSION: The Italian version of MIBS-4 provides a reliable instrument for quantifying interictal burden in Italian-speaking migraine individuals, enabling a more comprehensive evaluation of migraine and supporting individualized management.
BACKGROUND: Numerous studies have indicated that the neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) and the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) are reliable indicators of adverse...BACKGROUND: Numerous studies have indicated that the neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) and the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) are reliable indicators of adverse cardiovascular outcomes in patients with coronary artery disease and ischemic stroke. However, their association with early neurological deterioration (END) following intravenous thrombolytic therapy (IVT) in acute ischemic stroke (AIS) patients remains unexplored. The primary objective of this study was to investigate the relationship between NHR and MHR and the risk of END after IVT. METHODS: This study enrolled 433 stroke patients who underwent IVT. The NHR and MHR were calculated from routine blood tests obtained at emergency admission. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 4 points within 24 h post-IVT, while a modified Rankin Scale (mRS) score > 2 at 90 days indicated a poor functional outcome. Differences in clinical indicators between the END and non-END groups were compared, and risk factors for END were identified using multivariate logistic regression analysis. RESULTS: The NIHSS score, the rate of proximal artery occlusion, fasting glucose, the NHR, and the MHR were significantly higher in the END group compared to the non-END group. Multifactorial logistic regression analysis revealed that both the NHR (odds ratio 1.257; 95% CI: 1.107–1.427, P < 0.001) and the MHR (odds ratio 12.510; 95% CI: 3.144–49.781, P < 0.001) were significant risk factors for END, although they did not show a statistically significant association with poor functional outcomes. The areas under the receiver (AUCs) operating characteristic (ROC) curve for predicting END were 0.640 (95% CI: 0.562–0.719, P = 0.001) for NHR and 0.584 (95% CI: 0.512–0.657, P = 0.048) for MHR. Additionally, the optimal cutoff value for NHR was determined to be 1.848 × 109/mmol. CONCLUSION: Both NHR and MHR demonstrate strong predictive value for END, with NHR potentially serving as a superior predictor compared to MHR in AIS patients receiving IVT.
Palermo M, Cocilovo F, Trevisi G
… +10 more, Lucci Cordisco E, Di Martino L, Sonnini E, Albanese A, Doglietto F, Olivi A, Pola R, Gaetani E, Sturiale CL, Gemelli HHT study group.
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular disorder characterized by multisystem arteriovenous malformations (AVMs). Still, the influence of demographic factors and spec...BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular disorder characterized by multisystem arteriovenous malformations (AVMs). Still, the influence of demographic factors and specific pathogenic variants on systemic and cerebrovascular involvement remains incompletely defined. METHODS: We retrospectively included 142 patients with genetically confirmed HHT diagnosis. Systemic and neurovascular data were collected for each patient and stratified by age and sex. Then, we conducted univariate analyses for genotype-phenotype correlations after adjusting for age and sex. Afterwards, the significant associations were tested in multivariable logistic regression models to verify confounding effects. RESULTS: Hepatic AVMs and gastrointestinal bleeding increased significantly with age, whereas neurological manifestations showed no age dependency. In multivariable analysis for hepatic AVMs, increasing age was independently associated with hepatic involvement (p = 0.037), while ENG (p = 0.035) was associated with a lower likelihood of hepatic AVMs compared to ACVRL1. For brain AVMs, age, ENG gene, and variant truncation status were independent predictors, and the ACVRL1 c.277 C > T (p.Arg93*) mutation showed an independent association (p = 0.035). CONCLUSIONS: In HHT, age and gene-level effects are robust predictors of systemic AVM involvement, whereas mutation-specific associations remain difficult to evaluate. Larger multicenter studies are needed to validate variant-level risk and support personalized surveillance strategies.
Leukoencephalopathies encompass a heterogeneous group of acquired and genetic white matter disorders with variable clinical presentations. We report a case of adult-onset leukoencephalopathy caused by a heterozygous fram...Leukoencephalopathies encompass a heterogeneous group of acquired and genetic white matter disorders with variable clinical presentations. We report a case of adult-onset leukoencephalopathy caused by a heterozygous frameshift LAMB1 deletion in a 65-year-old woman presenting with progressive cognitive decline, mood changes, and migraine. Whole-exome sequencing identified a likely pathogenic variant, enabling a diagnosis after extensive metabolic and genetic workup. This case highlights the importance of considering LAMB1 variants in unexplained adult-onset leukoencephalopathies associated with cognitive decline.
Cuoco S, Russo M, Picillo M
… +41 more, Ricciardi C, Russillo MC, Amboni M, Arabia G, Avanzino L, Canesi M, Catania A, Ceravolo R, Cicero CE, Cilia R, Colangelo I, Dati G, De Micco R, De Rosa A, Di Fonzo A, Eleopra R, Fetoni V, Garavaglia B, Giglio A, Giuntini M, Invernizzi F, Lazzeri G, Marchese R, Nicoletti A, Pacchetti C, Panteghini C, Pilleri M, Radicati FG, Reale C, Scaglione C, Soricelli A, Stocchi F, Tessitore A, Vacca L, Volontè MA, Volpi G, Zangaglia R, Amato F, Barone P, Pellecchia MT, SIN Gender Neurology Study Group
BACKGROUND: Non-motor symptoms (NMSs) are highly prevalent in Parkinson’s disease (PD) and affect patients’ quality of life. Data on gender differences in NMSs are largely cross-sectional and derived from chronically tre...BACKGROUND: Non-motor symptoms (NMSs) are highly prevalent in Parkinson’s disease (PD) and affect patients’ quality of life. Data on gender differences in NMSs are largely cross-sectional and derived from chronically treated populations. Longitudinal evidence in early, levodopa-naïve PD patients remains limited. This study aims to longitudinally investigate gender differences in a wide range of NMSs in early-stage levodopa-naïve PD patients during the first 2 years following levodopa initiation. METHODS: This multicenter, prospective study enrolled 216 levodopa-naïve PD patients (139 men, 77 women) from 17 Italian movement disorder centers. Patients were evaluated at baseline and after 24 months (24 M) using validated scales. Baseline gender differences were explored using group comparisons. Gender effects at 24 M were examined using ANCOVA models adjusted for baseline values and levodopa dose at follow-up. RESULTS: At baseline, women showed greater cardiovascular and thermoregulatory autonomic dysfunction, higher anxiety, pain, fatigue, and worse quality of life, whereas men exhibited greater sexual dysfunction, daytime sleepiness, and better attentional performance. At the 24 M, gender differences persisted only for anxiety, pain, mobility, and emotional well-being, while additional significant differences emerged, including hypersexuality, visuo- spatial domain, and orthostatic-hypotension. Women exhibited greater symptom severity than men across all aforementioned variables, with the exception of hypersexuality. CONCLUSIONS: Gender significantly influences the expression and early evolution of NMSs in PD, independently of levodopa exposure. Gender-specific NMSs profiles are already evident in the first two years of treatment. These findings highlight the importance of integrating gender considerations into early assessment and personalized management of NMSs in PD.
INTRODUCTION: Anxiety disorders are common and disabling in Parkinson’s disease, however, systematic assessment is challenging in frontline clinical settings. The Movement Disorder Society Unified Parkinson’s Disease Rat...INTRODUCTION: Anxiety disorders are common and disabling in Parkinson’s disease, however, systematic assessment is challenging in frontline clinical settings. The Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) includes a single-item anxiety question, but its screening performance has not been definitively established. METHODS: The performance of the MDS-UPDRS anxiety-item was compared to a reference standard – the Hamilton Anxiety Rating Scale (HARS) administered in ON and OFF motor states. RESULTS: The MDS-UPDRS anxiety item score ≥ 1 predicted clinically significant anxiety with sensitivity/specificity of 76.5%/53.7% in the ON state and 65.0%/62.5% in the OFF state, while a score ≥ 2 yielded a sensitivity/specificity of 39.2%/93.3% ON and 22.5%/96.3% OFF. DISCUSSION: The MDS-UPDRS is a pragmatic clinical screen for anxiety, useful in triaging patients in need of comprehensive anxiety assessments. This study examines the screening performance of the MDS-UPDRS and provides a framework for how the scale can be operationalized in clinical settings to optimize identification of patients with clinically significant anxiety.
BACKGROUND: Transcranial ultrasound stimulation (TUS) is a non-invasive method that allows deep brain structures to be targeted, and it may benefit individuals with Alzheimer'sdisease (AD). We conducted a systematic revi...BACKGROUND: Transcranial ultrasound stimulation (TUS) is a non-invasive method that allows deep brain structures to be targeted, and it may benefit individuals with Alzheimer'sdisease (AD). We conducted a systematic review and meta-analysis to assess the effect of TUS on global cognitive function in mild-to-moderate AD, comparing focused transcranial pulse stimulation (TPS) with unfocused low-intensity pulsed ultrasound (LIPUS). METHODS: We searched PubMed, Scopus, Cochrane, and Web of Science for randomized controlled trials (RCTs) comparing TUS with sham stimulation. The primary outcome was the change in global cognitive function. Secondary outcomes included functional status,depressive symptoms, and safety. RESULTS: Three RCTs (N=84) were included. Pooled analysis showed that TUS did not significantly improve global cognition compared with sham (SMD=0.31, p=0.54). However,subgroup analysis showed a significant difference between modalities (p=0.047):unfocused LIPUS had a larger effect size (SMD=0.73) than focused TPS (SMD=0.17).Notably, significant cognitive improvement was observed in patients <70 years. Active treatment showed higher disease stabilization rates ("responders"), reduced depressive symptoms (specifically TPS, p=0.008), and improved cerebral perfusion without amyloid-related imaging abnormalities (ARIA). CONCLUSION: While pooled analyses did not show a global cognitive benefit, the results favoured unfocused LIPUS over focused TPS; TUS had an excellent safety profile and higher disease stabilization rates; the potential benefits in younger populations and the biological effects suggest that TUS is a promising adjunct that should be further optimized for stimulation. REGISTRATION: This review was registered on PROSPERO (CRD420251276660).
BACKGROUND: Several patient-reported outcome measures assess fatigue and fatigability in multiple sclerosis (MS), yet their psychometric properties require evaluation for appropriate selection. OBJECTIVE: This study exam...BACKGROUND: Several patient-reported outcome measures assess fatigue and fatigability in multiple sclerosis (MS), yet their psychometric properties require evaluation for appropriate selection. OBJECTIVE: This study examined the psychometric properties of two perceived fatigue measures (Modified Fatigue Impact Scale [MFIS)], Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F], one perceived fatigability measure (Pittsburgh Fatigability Scale [PFS]) and one combined measure (F-2-MS). METHODS: One hundred PwMS completed questionnaires assessing perceived fatigue, fatigability, and other secondary disease characteristics of MS. Analyses included floor and ceiling effects, reliability, and validity of the self-reported fatigue and fatigability measures. RESULTS: No measures showed floor or ceiling effects (< 20%). Internal consistency was good (α > .80) for all except F-2-MS. Only MFIS demonstrated low measurement error (standard error of measurement % = 8.78 (< 10%)). Convergent validity (r ≥ .80) was supported for MFIS with FACIT-F and F-2-MS. Discriminant validity was supported with all correlations < .80. Disability group differences were significant for MFIS, FACIT-F and PFS (F (10, 184) = 5.80, p = < .001), but not for F-2-MS. CONCLUSION: Minimal floor and ceiling effects, strong reliability, and good discriminant validity across all measures support their use in clinical and research settings. MFIS is most robust for perceived fatigue, and PFS for perceived fatigability.
BACKGROUND: Stroke remains one of the leading causes of death and disability worldwide. This population-based study aimed to examine trends in hospitalization, care processes and outcome of ischemic stroke patients in th...BACKGROUND: Stroke remains one of the leading causes of death and disability worldwide. This population-based study aimed to examine trends in hospitalization, care processes and outcome of ischemic stroke patients in the Veneto Region over a 25-year period. METHODS: We retrospectively analyzed hospital discharge records of Veneto population from 2000 to 2024, estimating hospitalization rates (HRs) for ischemic stroke, key care process indicators, and short-term mortality. Annual percentage changes were calculated to identify trends. RESULTS: Overall, 176,351 patients were discharged with a primary diagnosis of ischemic stroke, 84,515 were males (47.9%) and 91,836 were females (52.1%). From 2000 to 2024, the age-standardized HR declined from 172.1 to 96.0 per 100,000 inhabitants and 30-day mortality from 18.3% to 10.5%. The use of intravenous thrombolysis and mechanical thrombectomy increased markedly during the study period, reaching 21.1% and 10.0% in 2024, respectively. During the study period, a higher proportion of patients was admitted to neurology wards (from 37.6% to 68.9%) and to hospitals with a Stroke Unit (SU) (from 63.0% to 89.5%). The sex- and age-adjusted odds of 30-day mortality were lower after admission to neurology wards compared to other wards [OR 0.44 (95% CI: 0.43 to 0.46), p < 0.001] and among those admitted to hospitals with a SU compared to those without [OR 0.83 (95% CI: 0.80 to 0.86), p < 0.001]. CONCLUSION: From 2000 to 2024, the Veneto Region has experienced a significant reduction in HRs and mortality among patients with ischemic stroke, alongside improvements in admission settings and use of revascularization therapies.
BACKGROUND: In patients affected by central nervous system tumors not amenable to surgical resection, stereotactic needle biopsy today represents the only available diagnostic approach. Achieving a high diagnostic yield...BACKGROUND: In patients affected by central nervous system tumors not amenable to surgical resection, stereotactic needle biopsy today represents the only available diagnostic approach. Achieving a high diagnostic yield is essential for timely therapeutic decision-making. This study investigates the impact of intraoperative fluorophores (sodium fluorescein and 5-aminolevulinic acid) use on the diagnostic accuracy of stereotactic brain biopsies. METHODS: We retrospectively analyzed 516 stereotactic brain biopsies performed between 2015 and 2024. Data collected included fluorophore use, technique employed, histopathological and molecular results, and procedural outcomes. Diagnostic yield was defined as the proportion of conclusive diagnoses, in accordance with updated WHO classification criteria, while an extended definition, referred to as diagnostic success, included incomplete diagnoses; conversely, diagnostic failure was defined as inconclusive diagnosis. Statistical analyses included Chi-square testing and logistic regression. RESULTS: Fluorophores were used in 314 procedures (60.9%), while 202 (39.1%) were done without (control group). The diagnostic yield was 76.1% with fluorophores versus 68.8% without. When including incomplete diagnoses (diagnostic success) the accuracy rose up to 93.3% in the fluorophore group versus 78.2% in the control group. Fluorophore use was associated with a 69.3% relative reduction in diagnostic failure (p < .001). Logistic regression confirmed that fluorophores significantly increased the odds of diagnostic success (OR = 3.89, p < .001), without significant histology-based selection bias. CONCLUSION: Intraoperative fluorophores application significantly enhances diagnostic yield in stereotactic brain biopsies, independently of tumor histology. These results support a wider implementation of fluorescence-guided biopsy techniques to improve diagnostic accuracy in neuro-oncology.
BACKGROUND: The Composite Autonomic Symptom Score 31 (COMPASS-31) is a validated self-report questionnaire designed to assess autonomic symptoms across six domains. A Brazilian Portuguese version has not yet been formall...BACKGROUND: The Composite Autonomic Symptom Score 31 (COMPASS-31) is a validated self-report questionnaire designed to assess autonomic symptoms across six domains. A Brazilian Portuguese version has not yet been formally validated. METHODS: Following a standardized Mayo Clinic linguistic validation protocol, the COMPASS-31 was translated into Brazilian Portuguese. Twenty-one patients with disorders associated with autonomic symptoms and nine healthy controls completed both the English and Portuguese versions in randomized order, with a six-week interval between administrations. Reliability was assessed using kappa coefficients and Bland–Altman analysis. Validity was evaluated by comparing scores between patients and controls and by correlating the Portuguese and English versions. RESULTS: The Brazilian Portuguese version of the COMPASS-31 demonstrated good test–retest reliability and a strong correlation with the original English version (r = 0.784, p < 0.0001). Patients exhibited significantly higher total scores than healthy controls. Bland–Altman analysis showed good agreement, with 93.4% of values falling within the limits of agreement. CONCLUSIONS: The Brazilian Portuguese version of the COMPASS-31 is a valid and reliable instrument for assessing autonomic symptoms in both clinical and research settings.
Autoimmune cerebellar ataxia (ACA) is a complex neurological disorder characterized by immune-mediated damage to the cerebellum, which gives rise to ataxia symptom. Auto-neuronal antibodies play a crucial role in the dia...Autoimmune cerebellar ataxia (ACA) is a complex neurological disorder characterized by immune-mediated damage to the cerebellum, which gives rise to ataxia symptom. Auto-neuronal antibodies play a crucial role in the diagnosis of ACA. We present a case of an early 70s male whose main presenting symptom was subacute cerebellar ataxia. Enhanced cranial magnetic resonance imaging (MRI) did not detect any significant cerebellar lesions. The serum anti-neurochondroitin (NCDN) antibody IgG titer was 1:320, while the cerebrospinal fluid anti-NCDN antibody IgG titer was 1:1. After the administration of intravenous immunoglobulin (IVIG) and glucocorticoids, the patient’s symptoms were rapidly relieved. During a six-month follow-up period, the patient’s condition did not recur and it was maintained with low-dose oral glucocorticoids. Threrfore, It is recommended that auto-neurologic antibody testing be included into the routine diagnostic process for patients suspected of having ACA to enable early diagnosis. Early initiation of immunotherapy may significantly improve the prognosis of ACA patients.
BACKGROUND: The concept of time is crucial in managing neurological diseases, as it includes both the natural history of a disease and the urgency of treatment. This paper explores the aphorism "Time is Brain," emphasizi...BACKGROUND: The concept of time is crucial in managing neurological diseases, as it includes both the natural history of a disease and the urgency of treatment. This paper explores the aphorism "Time is Brain," emphasizing the importance of timely interventions, not only in ischemic stroke, and its applicability to many other neurological conditions. METHODS: The review synthesizes existing literature on the implications of time in various neurological conditions, including ischemic stroke, intracerebral hemorrhage, status epilepticus, and Guillain-Barré syndrome. It evaluates how timely treatment influences patient outcomes, highlighting key time-sensitive interventions and care bundles. DISCUSSION: Timely management, particularly in acute settings, is shown to correlate strongly with improved outcomes. For instance, in ischemic stroke, delays in treatment can lead to significant neuronal loss, quantifiable as "time is brain." Similarly, in intracerebral hemorrhage, early blood pressure management and other interventions within critical timeframes can significantly reduce morbidity. The review also addresses the importance of timing in the treatment of neurodegenerative diseases, where early interventions can change the disease trajectory. CONCLUSIONS: This paper underscores the multifaceted role of time in neurology. It advocates for the incorporation of time-sensitive strategies into clinical practice to enhance patient outcomes across various neurological disorders. Understanding and implementing timely interventions can optimize care and improve prognoses in acute neurological conditions.
Visual Snow Syndrome (VSS) is a rare neurological condition characterized by continuous static and dynamic visual dots that impair vision, despite preserved visual acuity. Its pathophysiology is still debated, but it is...Visual Snow Syndrome (VSS) is a rare neurological condition characterized by continuous static and dynamic visual dots that impair vision, despite preserved visual acuity. Its pathophysiology is still debated, but it is believed to involve cortical hyperexcitability and dysfunctional connectivity within visual processing networks. Pharmacological treatments have shown limited efficacy. In this work, we report the case of an 18-year-old female with VSS refractory to lamotrigine and topiramate, who underwent a novel non-invasive brain stimulation treatment using low-frequency (1-Hz) repetitive transcranial magnetic stimulation (rTMS) targeting the bilateral superior parietal lobule (SPL). The rTMS intervention consisted of ten daily sessions (5 days/week), with stimulation intensity individualized according to the phosphene threshold (PT). Clinical evaluations, fMRI, and EEG were performed before and after treatment. During the intervention, the PT progressively increased throughout treatment days. Post-intervention, the patient reported subjective clinical improvement. Furthermore, fMRI data showed reduced resting-state functional connectivity (rs-FC) between the SPL and the lingual gyrus (LG) bilaterally, while resting-state EEG power spectral density (PSD) showed a decrease in gamma-band power, particularly in the parieto-occipital region. These findings support the hypothesis that inhibitory rTMS may help restore physiological neural activity in visual processing networks, thereby alleviating VSS symptoms.