While several validated bedside screenings exist for oropharyngeal dysphagia (especially in stroke patients), a specific scale for oropharyngeal dysphagia has not yet been validated for patients with severe acquired brain injury. Accurately assessing oropharyngeal dysphagia in these patients within the rehabilitation setting is crucial for developing tailored treatment. This review aims to summarise the evidence concerning available bedside screening tests to evaluate oropharyngeal dysphagia, focusing specifically on their sensitivity and specificity. Severe acquired brain injury generate a high burden of disability and long-term care needs. The use appropriate tools for evaluation, diagnosis and treatment may help to prevent additional health problems and correlated costs. Although SWADOC is the only screening test specifically designed for oropharyngeal dysphagia in patients with severe acquired brain injury, other high-quality tests, such as the Gugging Swallowing Screen, the Two-Step Thickened Water Test, and the Sapienza Global Bedside Evaluation of Swallowing are available and appear promising in this field.

Background: Cluster headache is a severe primary headache disorder in which neuroimaging studies have suggested involvement of hypothalamic, limbic, and pain-related networks. Although hippocampal abnormalities have been reported in some studies, volumetric findings remain inconsistent and may depend on disease state, treatment exposure, chronicity, and imaging methodology. We explored whole hippocampus and hippocampal subfield volumes in medication-free patients with episodic cluster headache scanned interictally during an active bout. Methods: In this cross-sectional case–control study, 26 patients with episodic cluster headache (eCH) and 20 age- and sex-matched healthy controls underwent 3 T brain MRI. Patients were scanned during an active bout but outside acute headache attacks and had not received preventive treatment for at least three months before MRI acquisition. Automated hippocampus segmentation and subfield volumetry were performed using FreeSurfer 7.4.1, followed by visual quality control by two neuroradiologists. Group comparisons were adjusted for age, sex, and total intracranial volume. Multiple comparisons were addressed using Bonferroni correction for whole hippocampal volumes and false discovery rate (FDR) correction for subfield and clinical analyses. Results: No significant differences were detected between eCH patients and healthy controls in whole hippocampus or hippocampal subfield volumes after correction for multiple comparisons. Descriptive analyses showed numerically higher volumes in patients across several regions, but these effects were small to moderate and did not reach statistical significance. Exploratory analyses showed a nominal association between right fimbria volume and pain intensity; however, this association did not survive FDR correction. Conclusions: This study found no evidence of detectable hippocampal macrostructural differences in medication-free eCH patients scanned interictally during active bouts using 3 T MRI-based subfield volumetry. These null findings should not be interpreted as proof of preserved hippocampal structure, but rather as absence of measurable volumetric alterations within the limits of the present sample size, acquisition protocol, and analytical framework. Longitudinal and multimodal studies, including in-bout and out-of-bout assessments, higher-resolution imaging, and neuropsychological covariates, are needed to clarify whether hippocampal involvement in eCH is structural, microstructural, functional, or state-dependent.

Cluster headache (CH) is a primary headache disorder characterized by circadian rhythmicity and autonomic symptoms. While the posterior hypothalamus has been historically implicated, converging evidence now supports a distributed, network-level dysfunction involving cortical and subcortical regions. This study aimed to: (1) assess whole-brain cortical thickness alterations in episodic CH (eCH) during the bout period, (2) examine their associations with clinical burden, and (3) investigate resting-state functional connectivity patterns of cortical regions showing structural alterations. We investigated whole-brain cortical thickness and subcortical volumes in 26 patients with episodic CH scanned during the bout period but outside of attacks and 20 matched healthy controls (HC) using surface-based morphometry (FreeSurfer). Associations between cortical thickness and clinical variables (attack frequency, duration, disease history, and pain intensity) were assessed using general linear models corrected for multiple comparisons. Resting-state functional connectivity (FC) was further analyzed using seed-to-voxel correlations in the CONN toolbox, with seeds placed in cortical regions showing significant thinning. Compared with HC, eCH patients showed cortical thinning in the right inferior frontal gyrus (pars triangularis, BA45) and left superior frontal gyrus (BA9/10) (p < 0.05, Bonferroni correction). No significant subcortical volumetric differences were observed. Cortical thickness showed significant positive associations with clinical burden in associative parietal and occipital regions (p < 0.01, Bonferroni correction). Seed-based FC analyses revealed decreased coupling between the left superior frontal gyrus and right supramarginal cortex, but increased connectivity with the left precentral gyrus. Conversely, the right inferior frontal gyrus showed widespread hyperconnectivity with bilateral insulae, supramarginal, and sensorimotor cortices, and decreased connectivity with the right superior frontal region. These findings identify coexisting structural and functional alterations within frontal cortices and their distributed targets, suggesting a differential reorganization of frontal attentional and sensorimotor networks in eCH. The pattern of fronto-parietal disconnection and fronto-insular hyperconnectivity extends the network model of cluster headache beyond the well-established hypothalamic–thalamic dysregulation. Together, these results strengthen the concept of cluster headache as a network-level disorder involving both executive and sensorimotor control systems.

Cluster headache (CH) is a highly disabling primary headache disorder increasingly conceptualized as a disorder of distributed brain networks rather than an isolated trigeminovascular dysfunction. While structural and functional MRI studies have demonstrated persistent brain alterations outside the ictal phase, the role of white matter microstructural changes supporting network-level dysfunction remains incompletely understood. We investigated cerebral white matter microstructure in 27 patients with episodic CH examined during the bout outside active attacks using diffusion tensor imaging and tract-based spatial statistics (TBSS). Fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were compared between patients and healthy controls (N = 20) on a whole-brain white matter skeleton. Associations between diffusion metrics and clinical variables were explored using an ANCOVA-based TBSS framework. Compared with controls, patients with episodic CH showed widespread white matter microstructural alterations, characterized by reduced FA and AD and increased MD in multiple clusters involving long-range associative and projection pathways connecting frontal, parietal, temporal, subcortical, and cerebellar regions. No significant associations were observed between diffusion metrics and clinical variables, including disease duration, attack frequency, and pain intensity. White matter alterations predominantly affected pathways supporting large-scale pain-related and cognitive–affective networks, including fronto-parietal, thalamo-cortical, and cerebello-thalamo-cortical connections. These findings are consistent with a network-based model of CH and integrate coherently with recent multimodal MRI evidence of cortical thickness and functional connectivity alterations observed outside attacks in a largely overlapping cohort. Our results provide evidence of persistent white matter microstructural abnormalities in episodic CH outside the ictal phase, supporting the concept of CH as a disorder of distributed brain networks. White matter alterations may represent a structural substrate underlying enduring network dysfunction predisposing patients to recurrent attacks.

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. 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. 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

BACKGROUND:Audio-vestibular symptoms, including hearing loss and tinnitus, are increasingly reported in people with multiple sclerosis (pwMS), yet their clinical significance and underlying mechanisms remain unclear. Both central demyelination and peripheral involvement along the brain-cochlea axis have been proposed as potential contributors.This study aims to explore and describe pure-tone audiometry (PTA) findings in pwMS who screened positive for auditory complaints on the ENT-MS-12 questionnaire, and to summarize associated clinical and magnetic resonance imaging (MRI) features during follow-up. METHODS:In this prospective pilot study, 40 pwMS with relapsing-remitting MS were screened using the ENT-MS-12 questionnaire. Patients reporting auditory complaints and meeting predefined exclusion criteria were invited to undergo pure-tone audiometry (125-8000 Hz). Clinical data and MRI findings obtained within three months of audiometric testing were reviewed and compared with imaging from the previous year. RESULTS:Twenty-seven patients (67.5%) reported auditory symptoms. Eleven met the inclusion criteria and five consented to audiometric testing. All five patients showed a down-sloping audiometric configuration with elevated high-frequency thresholds, particularly at 6000-8000 Hz. Mean high-frequency thresholds were higher than age-matched reference values reported in the literature. During follow-up, four of five patients experienced clinical relapses; one of these also showed disease progression, auditory brainstem response abnormalities, and a temporal lobe lesion on MRI. CONCLUSIONS:In this pilot study, pwMS who reported hearing concerns and underwent audiometry presented subtle high-frequency auditory threshold elevations with a down-sloping audiometric pattern. These preliminary, descriptive findings suggest that incorporating auditory assessment may provide complementary clinical information in pwMS. Larger, controlled studies with electrophysiological testing and advanced neuroimaging are warranted to clarify the relevance and mechanisms of auditory involvement in multiple sclerosis, including potential central and peripheral contributions.

AimTo assess whether the timing of atogepant administration influences its tolerability and effectiveness over 12 weeks in patients with episodic and chronic migraine in a real-world setting.MethodsThis is a post-hoc analysis of the STAR study, a prospective, Italian, multicenter study evaluating atogepant 60 mg for migraine prevention. Data were collected at baseline (T0) and after the first 12 weeks (T3) of treatment. Patients were grouped by administration timing (morning vs. evening) and by administration with or without food. Changes in monthly headache days (MHDs), monthly migraine days (MMDs), and Migraine Disability Assessment (MIDAS) were measured. Tolerability was evaluated via adverse events (AEs). Linear mixed-effects models (LMMs) were used.ResultsEighty-one patients (86% females, mean age 50.8 ± 13.7 years) were included. At T3, MMDs decreased from 16.6 to 9.7 (p < 0.001) and MHDs from 19.8 to 11.9 (p < 0.001); 60% of patients achieved ≥50% reduction in MMDs. AEs occurred in 34 (42%) participants. Atogepant was taken in the morning by 57% and in the evening by 43% of patients. Fifty-seven out of 81 participants (70.4%) took atogepant with food. No significant differences in MMDs, MHDs, or AEs emerged between morning and evening users. Evening users had higher baseline MIDAS scores (estimated marginal means [EMMs]: 69.9 vs. 39.9, p = 0.034) that showed a greater reduction compared to morning users (F(1,63) = 6.29, p = 0.015), reaching similar final scores after 12 weeks (EMMs: 25.1 vs. 23.8). No difference in atogepant effectiveness and tolerability according to intake with or without food, except for a reduction in MHDs for patients who took atogepant without food (EMMs from 21.3 to 9.9 vs with food: EMMs from 18.4 to 12.7; F(1,79) = 8.553, p = 0.005).ConclusionsAtogepant significantly reduced migraine burden over 12 weeks in a real-world setting. Overall, the timing of atogepant administration did not affect its effectiveness or tolerability. However, a greater reduction in MIDAS scores was observed among evening users. Whether this reflects a pharmacological advantage or a ceiling effect remains unclear. Taking atogepant without food was associated with a significantly greater reduction in MHDs, whereas changes in MMDs and MIDAS scores did not differ between groups. Long-term and dedicated studies are needed to evaluate and confirm these findings.Trial RegistrationThe main study (STAR) was preregistered on clinicaltrial.gov, NCT06414044.

BackgroundThe improved prevention of migraine, driven by the introduction of calcitonin gene-related peptide (CGRP)-targeted therapies, has prompted the International Headache Society (IHS) to propose new goals in migraine management. This study aimed to evaluate the safety and effectiveness of atogepant for migraine prevention over 24 weeks, in accordance with the IHS-defined goals.MethodsThis is a multicenter, prospective, observational, real-world study on patients starting atogepant 60 mg for migraine prevention. We describe efficacy and safety outcomes at weeks 9-12 (T3) and 21-24 (T6) relative to baseline (T0) from the initiation of atogepant treatment. We also report the proportion of patients achieving migraine freedom, optimal, modest or insufficient control according to the IHS position paper categories.ResultsOne hundred twenty-eight (n = 128) patients (63 (49.2%) with chronic migraine, 115 (89.9%) female, aged 48.3 ± 13.3 years) from 17 centers were analyzed. Monthly migraine days decreased from 16.5 ± 8.5 at T0 to 8.0 ± 8.4 at T3 (p < 0.001 vs. T0) and 8.6 ± 9.2 at T6 (p < 0001 vs. T0, p = 0.265 compared to T3). Overall, 64.8% of patients were responders (at least 50% reduction in monthly migraine days from T0) at T3 and 61.7% at T6; 81.9% of responders at T3 maintained the responder status at T6, while 24.4% of patients among non-responders at T3 became responders at T6. At T3 and T6, 39.1% of the entire cohort achieved at least optimal migraine control (20.6% in chronic migraine and 56.9% in episodic migraine).ConclusionsThe STAR study demonstrates, in a real-world setting, the safety and the sustained effectiveness of atogepant 60 mg over 24 weeks and indicates that more than one-third of treated patients can achieve at least optimal disease control, with markedly better outcomes in episodic than in chronic migraine.Trial RegistrationThe study was preregistered on clinicaltrial.gov, NCT06414044.

BACKGROUND:Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway represent an effective preventive treatment for chronic migraine, including in patients with multiple prior therapeutic failures. However, a substantial proportion of patients exhibit a suboptimal or delayed response. The role of personality traits in modulating treatment response remains poorly understood. METHODS:In this prospective observational study, adults with chronic migraine received anti-CGRP monoclonal antibodies and were followed for 12 months. Monthly headache days (MHDs), monthly acute medication use (MAM), and disability scores (MIDAS and HIT-6) were recorded at baseline and at 3, 6, and 12 months. Responders were defined as patients achieving a ≥50% reduction in monthly headache days (MHDs) compared with baseline. Changes in disability measures were evaluated as secondary clinical outcomes. Personality traits were assessed using the Millon Clinical Multiaxial Inventory-III. RESULTS:Thirty-eight patients were included, of whom 71% had medication overuse headaches. Responder rates increased over time (31.6% at 3 months and 39.5% at 12 months). Histrionic traits (37.5% vs. 6.7%, p = 0.048) and dysthymic features (21.4% vs. 0%, p = 0.046) were significantly more prevalent among non-responders. CONCLUSIONS:Histrionic and dysthymic personality features were associated with a lower likelihood of response to anti-CGRP therapy in patients with chronic migraine. Given the exploratory design, limited sample size, and absence of correction for multiple comparisons, these findings should be considered preliminary and hypothesis-generating. Further studies in larger cohorts are needed to confirm these observations.

Medication Overuse Headache (MOH) occurrence during migraine preventive therapy is poorly known. The present study aims at identifying the rate and factors influencing MOH development in patients with Chronic Migraine (CM). Patients with a diagnosis of CM without MOH were consecutively recruited and followed at least three times for 1 year under preventive therapy. The number of headache days and the use of acute medication were recorded; the occurrence of MOH was considered as the main event. Kaplan–Meier curves were used to determine the time of the event. After the third follow-up patients were censored. Proportional hazards Cox regression was used to identify predictors of MOH among demographic variables (e,g. age), main comorbidities (e.g. sleep disorders, epilepsy, thyroid dysfunctions), migraine features (e.g. aura, number of previous preventive therapies, headache days and number of medications). We recruited 260 first-visit patients with CM. 46 patients (17.70

Background/Objectives: Photophobia is one of the most prevalent migraine symptoms, both during and outside of attacks, but its pathogenesis is unknown. The posterior thalamic nuclei may directly affect ambient light discomfort. This study examined the link between photophobia and the structure and morphometry of the thalamus and its subregions, including the lateral geniculate nuclei and pulvinar subnuclei. Methods: Twenty patients with episodic migraine without aura (MO) and 20 healthy controls (HCs) underwent high-resolution T1-weighted magnetic resonance imaging and comprehensive ophthalmological assessment. Patients were scanned interictally and none of them were under preventive therapy. Volumetric segmentation encompassed the whole thalamus and the lateral geniculate nuclei and pulvinar subregions. Interictal photophobia was evaluated using a visual analogue scale, ranging from 0 to 10. All thalamic and subregion volumes were used as independent variables and photophobia levels as dependent variables in general linear models. The model considered gender as a factor and total intracranial volume as a covariate. Results: No statistically significant differences were observed in the overall thalamic volume or in any of its subregions between MO patients and healthy controls (punc > 0.05). No relationships emerged between thalamic volumes and interictal subjective photophobia levels (p > 0.05). Conclusions: Our results suggest that photophobia is not linked to thalamic macroscopic volumes alterations during the interictal phase of MO patients. Further research is needed to determine whether these results could be extended to patients with migraine with aura or during other phases of the migraine cycle.

BACKGROUND:Multiple sclerosis (MS) often causes impairment in working memory (WM), information processing speed (IPS), and verbal memory (VM). These deficits are linked to disrupted neural oscillatory activity. Transcranial alternating current stimulation (tACS), which modulates cortical oscillations, may hold promise for treating cognitive impairment in MS. OBJECTIVES:To evaluate online and offline effects of gamma (γ)-tACS on WM, IPS, and VM while assessing changes in brain rhythms using electroencephalography (EEG). METHODS:Thirty-six MS patients with single-domain impairment in WM (12), IPS (13), or VM (11) underwent γ-tACS and sham-tACS over the left dorsolateral prefrontal cortex (DLPFC) (WM, IPS) or precuneus (VM). Cognitive performance was assessed pre-tACS (T0), during (T1), and post-tACS (T2) using the Digit Span Backward (DSBW) for WM, Symbol Digit Modalities Test (SDMT) for IPS, and Rey Auditory Verbal Learning Test (RAVLT) for VM. EEG was recorded at T0 and T2 to analyze local power spectral density and local-to-global connectivity. RESULTS:DSBW, SDMT, and RAVLT scores transiently improved during γ-tACS and not during sham. IPS-impaired patients showed a reduction in spectral power across all frequency bands, at the stimulation site, post-DLPFC γ-tACS. CONCLUSION:γ-tACS briefly improves WM, IPS, and VM in MS patients, warranting further trials of this non-invasive intervention.

BackgroundThe prevalence of cranial nerve involvement in Multiple Sclerosis (MS) varies across studies. It has been speculated that first presentation of disease with cranial nerve involvement – except for optic neuritis – may be associated with milder progression.AimThis study compares the clinical outcome of patients with MS in a 4-year follow-up of patients with initial symptoms of optic neuritis (ON) versus those with other cranial nerve (OCN) involvement.Materials and methodsRetrospective analysis of MS patient database of a tertiary referral university MS center. We included treatment-naïve patients diagnosed with MS according to the revised McDonald criteria, who presented with their first clinical symptoms suggestive of ON or OCN. Patients were required to have regular clinical and radiological follow-up visits (at least two outpatient visits per year and one annual 1.5T MRI), and no comorbidities. The number of relapses and the Expanded Disability Status Scale (EDSS) scores were assessed at six-month intervals during clinic visits. The primary outcome was the number of relapses observed during the study period, comparing the ON and OCN groups. Several statistical analyses were performed, including multiple linear regression, Cox proportional hazards model, one-way ANOVA, and odds ratios, to compare the groups.ResultsOf the 84 patients included, none had comorbities (e.g., overlap with other inflammatory diseases, neoplasm etc.). Fifty-five presented with ON and 29 with OCN (e.g., diplopia, trigeminal pain, hearing or vestibular symptoms) at onset. Patients with ON were younger than those with OCN symptoms (p = 0.02), had a higher risk of relapse (more than two relapses) (OR: 1.53) and greater disability (incremental EDSS) over the 4-year follow-up (OR: 1.60).ConclusionPatients with OCN involvement at the onset experienced fewer relapses and had better EDSS scores at the 4-year follow-up compared to those with ON at onset. These preliminary findings suggest that MS onset with OCN involvement may be associated with a more favorable disease course.

Among non-pharmacological approach for chronic migraine (CM), Short-Term Psychodynamic Psychotherapy (STPP) is suggested in CM and, particularly, in interrupting medication overuse (MO). In this study, we aim at identifying clinical predictive factors to identify CM patients who could more likely respond to STPP. We designed a prospective real-world observational study on CM patients undergoing STPP. We collected clinical data related to migraine burden (baseline headache days, number of acute medications used, MIDAS, HIT-6), as well as psychiatric comorbidities (though MINI) and mentalization level obtained by the STPP first interview phase (called BPI) to use them as predictive factors by univariate and discriminant function analysis at 3 (early) and 6 months (only sustained response). We recruited 119 patients (mean age 39.90 ± 14.4, F = 102); 113(94

Ofatumumab (OFA) is a highly effective therapeutic option for multiple sclerosis (MS), but real-world data on its efficacy and safety remain limited. We evaluated the real-world efficacy and safety of OFA in patients with MS and explored the predictive value of frailty. We retrospectively collected clinical and MRI data from 12 MS centers in Central Italy, including patients who initiated OFA between April 2022 and January 2024. We assessed annualized relapse rate (ARR), clinical relapses, radiological activity, and safety. Frailty, defined as increased vulnerability due to age-related health deficits, was measured using a frailty index (FI). The study was approved by the local Ethics Committee (No. 6357). A total of 242 patients with MS were included (66.8

OBJECTIVE:To investigate the characteristics and nature of headache in a population of patients with acromegaly. BACKGROUND:Headache is frequently described by patients with pituitary adenomas. Although it is mainly considered a secondary disorder, it can persist despite effective therapy for pituitary disease. A proper description of headache according to the subtype of pituitary adenoma is not available in literature. In this light, we aimed to analyze headache characteristics in a population of patients with acromegaly. METHODS:In this registry-based retrospective cohort study, headache features were collected through a structured telephone interview. The clinical picture of each patient was classified according to the third edition of the International Classification of Headache Disorders criteria. We carefully investigated the time course and the relationship of headache with acromegaly. RESULTS:Out of 39 enrolled patients, 27 (69%) reported headache. Six patients (15%) fulfilled secondary headache criteria, with complete headache resolution after acromegaly treatment. In all, 21 patients (54%) met the criteria for a primary headache: fourteen had episodic migraine, four had chronic migraine, and three had tension-type headache. No trigeminal autonomic cephalalgias were observed. The presence of primary headache significantly reduced the time to diagnosis of acromegaly (mean [standard deviation] 2.1 [2.5] vs. 4.3 [3.5] years, p = 0.007). The occurrence of primary headache was similar in patients with macroadenoma compared to patients with microadenoma (14 [67%] vs. 7 [33%], χ2 = 0.591, p = 0.400), while its course was not significantly influenced either by the acromegaly treatment (p = 0.670) or the achievement of biochemical control (p = 0.490). CONCLUSION:Secondary headache was found only in a small percentage of our patients. Most of them had a primary headache with a high prevalence of migraine, suggesting that acromegaly might act as a trigger for this disorder. Considering the potentially disabling nature, primary headaches in patients with acromegaly require careful evaluation and personalized management.