Background: Headache is the most common presenting symptom of intracranial hypotension (IH), and it usually has orthostatic features. However, the outcome of IH and the persistence and characteristics of headache are still overlooked.Methods: In this cohort study, patients diagnosed with IH in our institute between 2018 and 2024 were included. Demographical and clinical data, headache characteristics, etiology, type of treatment (epidural blood patch (EBP), surgical or conservative), and MRI findings were collected. We conducted follow‐up visits on headache characteristics and the persistence of headache ≥ 12 months of EBP/conservative treatment.Results: Forty‐five patients with a diagnosis of IH were included (mean age of 53.0 ± 14.9 years); 35 (77.8%) were diagnosed with spontaneous intracranial hypotension (SIH) and 10 (22.2%) with secondary IH. EBP was performed on 22 patients (48.9%). Headache was the most common symptom at presentation, in 38/45 patients (84.4%), with orthostatic features in 32 (71.1%). Forty‐four patients (97.8%) had brain MRI abnormalities. Follow‐up visits were conducted after 31.6 ± 15.7 months; 28/41 (68.3%) patients reported headache during the first 12 months, and 22/41 (53.7%) ≥ 12 months. Headache persistence for ≥ 12 months was significantly lower in patients who received EBP (27.3%) compared to those who did not (63.2%) (p = 0.021). Logistic regression showed that receiving EBP was the only factor significantly associated with reduced likelihood of persistent headache for ≥ 12 months (OR = 0.082, 95% CI [0.007,0.903], p = 0.041). Radiological features differed significantly between patients with SIH and those with secondary etiologies.Conclusion: A large proportion of patients with IH continue to experience headache beyond one year; EBP was the only predictor of headache persisting ≥ 12 months.

Background/Objectives: Fabry disease (FD) is an inborn error of the glycosphingolipid metabolism with variable kidney, heart, and central nervous system (CNS) involvement. CNS-related FD manifestations include early ischemic stroke and white matter lesions (WMLs) related to cerebral small-vessel disease (CSVD), possibly resulting in cognitive impairment. We studied 40 adult FD patients (17 male) to assess: (i) prevalence of cerebrovascular and cognitive manifestations in FD and their correlation with heart and renal involvement; and (ii) the potential value of serum neurofilament light chain (NfL) levels as an indicator of WMLs in FD. Methods: Patients underwent detailed diagnostic assessment related to FD, also including Mainz Severity Score Index (MSSI), neuropsychological tests, brain MRI to assess WMLs by the modified Fazekas score (mFS), and NfL determination by single-molecule array (SiMoA) (n = 22 FD patients vs. 15 healthy controls). Results: Overall, 4 FD patients had a history of ischemic stroke and 13/32 patients (40.6%) had an mFS ≥ 1. Almost two-thirds of FD patients (27/39, 69.2%) showed impairment on at least one cognitive test. On univariate analysis, only a reduction in estimated glomerular filtration rate was associated with an increased likelihood of having WMLs on brain MRI. Serum NfL levels were higher in FD patients vs. controls, with a trend toward significance (p = 0.08). Conclusions: Mild-to-moderate CSVD is a characteristic brain “signature” in FD patients. Both cardiac and renal involvement correlate with WML load, but only renal involvement appears to be predictive of CNS damage. Brain microvascular damage is associated with mild cognitive impairment in FD, and serum NfL might represent a potential biomarker of CSVD in FD.

Background and Purpose: Despite the wide use of dopamine receptor blocking agents (DRBAs) in Huntington disease (HD), neuroleptic malignant syndrome (NMS) is rarely described in this population. The aim of this study was to assess NMS prevalence in a large cohort of HD patients and explore the main associated risk factors.Methods: In 2023, an HD patient was admitted to our neurology department due to NMS. Starting from the case description, we performed a narrative review of the literature of NMS cases in HD, reviewed data from the fifth dataset of the Enroll‐HD (a longitudinal, observational, global study of families with HD) study (PDS5) selecting HD patients treated with DRBAs and/or tetrabenazine (TBZ) who presented at least one of the core symptoms of NMS (rigidity and hyperthermia), and collected data to investigate prevalence of NMS and identify risk factors.Results: In the Enroll‐HD PDS5 dataset, we identified 5108 of 11,569 HD patients who were undergoing DRBA and/or TBZ treatment. Only one patient, a Caucasian man of 46 years, undergoing clozapine and valproate treatment, had a registered diagnosis of NMS.Conclusions: NMS in HD patients is seldom described. This could be due to an underestimation of this condition. There are no available objective NMS diagnostic criteria at present, and the existence of atypical forms of NMS further complicates diagnosis. Advanced disease stage, rigid–akinetic phenotype, abrupt therapy changes, polytherapy, and dehydration are key risk factors, most of which are preventable through awareness and caution in managing medications in the HD population.

Background: Sleep disturbances in RFC1‐spectrum disorders remain unexplored. This study aimed to investigate the prevalence and characteristics of sleep disorders in patients with RFC1‐spectrum disorders and their impact on quality of life (QoL).Methods: Patients underwent a comprehensive sleep assessment using validated questionnaires, polysomnography, and QoL evaluation.Results: Among 16 participants, 15 (94%) had obstructive sleep apnea: severe in four, moderate in nine, and mild in two. Restless legs syndrome affected 12 patients (75%), with moderate‐to‐severe symptoms in 11. Periodic limb movements during sleep exceeded the clinical threshold in 10 patients (63%). Rapid eye movement (REM) sleep behavior disorder was identified in 1 patient. Subjective assessments revealed poor sleep quality in 11 patients (69%) and insomnia in 10 (63%). All patients exhibited reduced QoL. Reduction in slow‐wave sleep and REM sleep are associated with increased clinical severity.Conclusion: RFC1‐spectrum disorders are associated with a high prevalence of sleep disorders and impaired QoL, highlighting the need for screening. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objectives: Super‐refractory status epilepticus (SRSE) is a neurological emergency with high morbidity and mortality. Cenobamate, a novel antiseizure medication, may be helpful in managing SRSE, but evidence is limited. Methods: This retrospective case series reports the use of cenobamate as add‐on therapy in the management of three cases of SRSE. Results: Median age at status epilepticus (SE) onset was 28 years (range 27–75). The etiologies of SRSE included one case of febrile infection‐related epilepsy syndrome (FIRES), one patient with a probable genetic etiology (SCN7A variant of uncertain significance), and one case of unknown etiology. Cenobamate was introduced at a median of 27 days (range 13–103) after SE onset. Resolution of SRSE was observed after a median of 7 days (range 3–30) once cenobamate was started. Median dose of cenobamate at SRSE cessation was 25 mg/day (range 12.5–50 mg/day), and the median maintenance dose at the time of discharge was 200 mg/day (range 100–400 mg/day). Two patients died and one patient achieved functional independence. No severe medication side effects, specifically drug reaction with eosinophilia and systemic symptoms (DRESS), were observed. Discussion: Cenobamate may have a role in the management of SRSE. Further studies are needed to define the optimal timing of initiation, titration strategy, and target dose of cenobamate in the context of SE.

Background: Fabry Disease (FD) is an X-linked lysosomal disease, in which, unlike other X-linked disorders, most female carriers manifest signs or symptoms for unknown reasons. Objectives: Herein, we aimed to test the potential role of X-chromosome inactivation (XCI) in leukocytes as a prognostic biomarker of disease in FD female carriers. Moreover, we explored if levels of X-inactive-specific transcript (Xist), a long non-coding RNA driving XCI, were detectable in the leukocytes of FD female carriers. Methods: We tested the XCI pattern in leukocytes on 33 consecutive females carrying pathogenic GLA variants. Disease severity was defined using the Mainz Severity Score Index (MSSI). Xist levels in leukocytes were assessed by real-time PCR and compared to the levels of 22 controls. Results: XCI was obtained for 31 female patients, finding 16 skewed (51.6%) individuals. Global MSSI did not differ in skewed vs. non-skewed FD carriers. In skewed FD females, the renal function and mean cardiologic MSSI subscore were significantly worse, and systemic arterial hypertension was more frequent. Xist levels detected in leukocytes were similar between female patients and controls, and did not differ by phenotype or XCI status. Conclusions: A skewed XCI pattern in leukocytes may represent a prognostic biomarker of worse renal and cardiac outcomes in female FD carriers.