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Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objective: To present cases of ptosis in HIV-1 patients on long-term antiretroviral therapy (ART) and review the existing literature., Methods: Five HIV-1-positive patients with slowly progressive bilateral ptosis underwent a comprehensive diagnostic evaluation, including imaging studies, neurophysiological testing, muscle biopsy, and genetic analysis. A literature review was conducted., Results: On clinical examination, all patients presented with bilateral symmetrical non-fatigable ptosis, three exhibited facial lipoatrophy and two also had mild multidirectional ophthalmoparesis and all had ocular abnormalities in Hess screen test. Additionally, one patient displayed proptosis, three had floppy lower eyelids, and four presented with exotropia. Anti-acetylcholine receptor antibodies were negative in all patients. Brain magnetic resonance imaging (MRI), motor unit potential analysis, and single-fiber electromyography were unremarkable. Orbital MRI revealed introrbital fat expansion in one patient, and limb muscle biopsies were inconclusive in two cases. Blood genetic testing for chronic progressive external ophthalmoplegia was negative in all patients. A total of 30 similar cases have been documented in the literature, with some studies reporting key findings such as muscle histology indicative of mitochondrial myopathy, MRI revealing patchy extraocular muscle hyperintensity, and muscle genetic testing identifying mitochondrial deoxyribonucleic acid (DNA) deletions. Ptosis surgical repair appears to be the most effective treatment., Conclusion: HIV patients on long-term ART may develop ocular muscle involvement due to mitochondrial dysfunction, with bilateral ptosis being the primary manifestation. Diagnosis is challenging and requires the exclusion of other conditions. Ptosis surgery can significantly improve quality of life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: C9orf72 gene repeat expansion (C9RE) is the most frequent gene variant associated with amyotrophic lateral sclerosis (ALS). We aimed to study the phenotype of motor neurone disease (MND) patients with C9RE in a Portuguese cohort., Methods: Demographical and clinical data of MND patients with (C9RE+) and without C9RE were compared. ALS al Rating Scale-Revised (ALSFRS-R) and Edinburgh Cognitive and Behavioural ALS Screen (ECAS) were used to evaluate functional and cognitive performance, respectively. Survival analysis was performed using Kaplan Meier log-rank test and Cox proportional hazards model., Results: We included 761 patients of whom 61 (8.0 %) were C9RE+. C9RE+ patients had a higher frequency of ALS (95.1 vs 78.4 %, p = 0.002), and lower frequency of progressive muscular atrophy (3.3 vs 16.7 %, p = 0.006). C9RE+ was associated with earlier age of onset (58.1 vs 62.6 years, p = 0.003) and more frequent MND family history (65.5 vs 11.4 %, p < 0.001). Gender, ethnicity, onset site, diagnostic delay, disease progression rate until diagnosis (ΔF), ALSFRS-R and time until non-invasive ventilation did not differ between groups. Cognitive/behavioural symptoms and ECAS did not differ between groups, except a worse visuospatial score in C9RE+ group (p = 0.035). Death rate was 1.8 and 1.6 times higher in C9RE+ patients with MND and ALS, respectively. Significant survival prognostic factors in C9RE+ group were diagnosis delay (HR = 0.96, 95 %CI 0.92-0.99, p = 0.008) and ΔF (HR = 1.93, 95 %CI 1.26-2.96, p = 0.002)., Conclusion: Our study corroborates most previous cohorts' findings, but harbours some singularities regarding onset site, phenotype, and cognitive profile, that contribute to a better understanding of C9RE epidemiology., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Atherosclerotic plaque fluorine-18 sodium fluoride ( 18 F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18 F-NaF uptake., Methods: Subjects with high CV risk but without CV events underwent 18 F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18 F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20 mg/daily for six months, and re-evaluated by 18 F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18 F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation., Results: Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7 ± 18.7% for ASCVD systems. After six months of rosuvastatin treatment (n = 34), low-density lipoprotein cholesterol lowered from 133.6 ± 33.8 to 58.8 ± 20.7 mg dL -1 (60% relative reduction, p < 0.01). There was a significant 19% reduction in maximum plaque 18 F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p < 0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p = 0.003)., Conclusion: In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18 F-NaF uptake was significantly reduced after six months of high-intensity statin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients., Material and Methods: A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed., Results: Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited., Conclusions: Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier., Competing Interests: Declaration of competing interest Miguel Oliveira Santos and Mamede de Carvalho received support from Sanofi. The other authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Competing Interest None.

Background: Some amyotrophic lateral sclerosis (ALS) patients on continuous non-invasive ventilation (NIV) develop dysphagia demanding a clinical decision regarding gastrostomy., Material and Methods: We have analyzed a cohort of seventy-four ALS patients dependent on continuous NIV (>22 h/day) and without feeding tube., Results: Three patients underwent to gastrostomy due to dysphagia progression. The other patients were categorized in two groups according to question 3 ("swallowing") of the ALSFRS-R scale: group 1 (G1), score = 4 (normal), and group 2 (G2), score = 3 or 2 (mild-moderate dysphagia). G2 included 29 (40.8%) patients. Survival was similar in G1 and G2 (p = 0.12). Disease duration (p < 0.0001) and ALSFRS-R progression rate (p = 0.008) at NIV >22 h/day were predictors for survival in G1, but not for G2. Gender, onset-region, and age at NIV >22 h/day did not influence survival., Conclusions: Our findings are relevant when discussing gastrostomy with these patients., Competing Interests: Declaration of Competing Interest The authors report there are no competing interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Three-dimensional printing (3D) has emerged as an alternative to imaging to guide left atrial appendage closure (LAAC) device sizing., Aims: We assessed the usefulness of 3D printing compared to a standard imaging-only approach for LAAC., Methods: We identified studies comparing an imaging-only with a 3D printing approach in LAAC. A fixed-effects meta-analysis was performed targeting a co-primary endpoint of disagreement in device sizing and leaks., Results: Eight studies that assigned 283 participants to an imaging-only approach and 3D printing approach (145 patients) were included. 3D printing significantly reduced the risk of the co-primary endpoint (risk raio (RR) = 0.19; 95% confidence interval (CI) 0.09-0.37), with consistency across the studies (I2 = 0%). Individually, both device size disagreements [RR 0.13 (95% CI 0.06-0.29), P < 0.001] and leaks [RR 0.24 (95% CI 0.09-0.64) P = 0.004] were reduced under a 3D printing modeling strategy., Conclusion: Compared with an imaging-only strategy, 3D printing is associated with reduction in device size disagreements and leaks., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Cardiac sarcoidosis (CS) is clinically diagnosed in 5% of patients with sarcoidosis but imaging studies suggest higher prevalence. We evaluated the prevalence, clinical manifestations, and cardiovascular outcomes of CS, diagnosed through 18 F-Fluorodeoxyglucose positron emission tomography ([ 18 F]FDG-PET), in a southern European population., Methods: Retrospective single-centre study of patients screened for sarcoidosis with [ 18 F]FDG-PET. Subjects with histological confirmation were divided in two groups, CS or extracardiac sarcoidosis, according to Heart Rhythm Society's criteria. Primary endpoint was defined as the composite of heart failure hospitalizations, uncontrolled arrythmias, pacemaker implantation, and cardiovascular (CV) mortality. Secondary outcomes included each component and all-cause mortality., Results: From 128 patients with biopsy-proven extracardiac sarcoidosis, 10.2% had probable CS, 54% without symptoms of cardiac involvement. Ten patients had suggestive [ 18 F]FDG uptake patterns, three subjects had an indicative cardiac magnetic resonance (CMR). Patients with probable CS had significantly higher prevalence of coronary and valvular disease, heart failure, and atrial fibrillation compared with those without cardiac involvement. During a mean follow-up of 4.0 SD2.7 years, the primary outcome occurred more frequently in patients with probable CS (53.8% vs. 3.5%; HR 25.45; 95% CI 5.27-122.9; p < 0.01) as well as heart failure hospitalizations (46.2% vs. 0.9%), uncontrolled arrhythmias (23.1% vs. 1.7%) and pacemaker implantation (23.1% vs. 0.9%) (p < 0.01 for all). All-cause mortality was three-fold higher in probable CS, despite the absence of statistical significance (15% vs. 5%, p = 0.15)., Conclusions: Among patients with biopsy-proven sarcoidosis, cardiac involvement detected by [ 18 F]FDG-PET or CMR is associated with a higher risk of CV events, irrespective of symptoms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: This study evaluates diagnostic accuracy of the proposed 'Gold Coast' (GC) diagnostic criteria for amyotrophic lateral sclerosis (ALS)., Methods: Five European centres retrospectively sampled consecutive patients referred for electromyography on suspicion of ALS. Patients were classified according to the GC criteria, the revised El Escorial (rEE) criteria and the Awaji (AW) criteria without and with the 'Possible' category (+ Poss). Reference standard was ALS confirmed by disease progression at follow-up., Results: Of 404 eligible patients 272 were diagnosed as ALS, 94 had mimicking disorders, 35 were lost for follow-up, and three had insufficient data. Sensitivity for the GC criteria was 88.2% (95% CI: 83.8-91.8%), which was higher than for previous criteria, of which the AW + Poss criteria reached the highest sensitivity of 77.6% (95% CI: 72.2-82.4%) (p < 0.001). Specificity was high for all criteria. The increase in sensitivity for the GC criteria was mainly due to the inclusion of 28 patients with progressive muscular atrophy (PMA)., Conclusions: The simpler GC criteria increase the sensitivity, primarily due to considering PMA as a form of ALS with high specificity preserved., Significance: This validation study supports that GC criteria should be used in clinical practice and may be used for inclusion in trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Porphyrias are a set of rare inherited metabolic disorders, each of them representing a defect in one of the eight enzymes in the haem biosynthetic pathway resulting in the accumulation of organic compounds called porphyrins. Acute hepatic porphyrias (AHP) are those in which the enzyme deficiency occurs in the liver, of which acute intermittent porphyria is by far the most common subtype. Neurology of the AHP is still challenging in practice, and patients rarely receive the correct diagnosis early in the disease course. For AHP, which primarily affects the central and peripheral nervous system, the cause of symptoms seems to be the increased production of neurotoxic precursors, in particular delta-aminolaevulinic acid and porphobilinogen. Neurological complications usually result from severe episodes of acute attacks. The neurologic hallmark of porphyrias is an acute predominantly motor axonal neuropathy resembling a Guillain-Barré syndrome that generally occurs after the onset of other clinical features such as abdominal pain and central nervous system manifestations. Neuropsychiatric syndromes, seizures, encephalopathy, and cerebrovascular disorders are among the possible central nervous system presentations. Therapeutic approach to AHP is divided into management and prophylaxis of an acute attack, including long standing options such as intravenous hematin and new therapeutic agents such as givosiran., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Amyotrophic lateral sclerosis (ALS) is now recognized as a multisystem neurodegenerative disorder, comprising autonomic dysfunction. We aimed to assess sudomotor function in ALS by measuring the electrochemical skin conductance (ESC)., Methods: Thirty-one ALS patients [median age of 62 years (1st-3rd interquartile range - IQR, 56-72), male 71%] were prospectively compared with 29 healthy controls, matched for age and sex. We analysed ESC results from hands and feet, bilaterally., Results: A total of 120 ESC recordings were obtained. Hands and feet ESC measurements were significantly lower in patients compared with controls [64 μS (1st-3rd IQR, 57-58) versus 78 μS (1st-3rd IQR, 70.5-84), p < 0.001 and 76 μS (1st-3rd IQR, 68-83) versus 81 μS (1st-3rd IQR, 78-86), p = 0.008, respectively]. In ALS group, no differences were observed between spinal and bulbar-onset forms for hands and feet results (p > 0.05). Hands and feet ESC measurements did not correlate also with disease duration, total ALSFRS-R scale, or ALSFRS-R progression rate (all p > 0.05)., Conclusion: ESC is a non-invasive, fast and quantitative method suitable for assessing sudomotor function. ALS patients revealed a decreased function in upper and lower extremities., Significance: Sudomotor dysfunction is part of the ALS manifestations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions affecting the digestive system, comprising two main distinctive entities, ulcerative colitis (UC) and Crohn's disease (CD). Besides gastrointestinal manifestations, IBD causes extraintestinal manifestations in the central and peripheral nervous system. The incidence of neurological complications in IBD ranges from 0.25% to 47.5%. The pathophysiology of neurological manifestations of IBD is mostly immune mediated, but dysfunction of the brain-gut axis, arterial and venous thromboembolism, infections, nutritional deficiencies and side-effects of medications (steroids, metronidazole, sulfasalazine, anti-TNF-α, anti-integrin antibodies) are other contributory mechanisms. Patients with IBD have an increased risk of arterial and venous stroke, mainly during periods of exacerbations. Vasculitis is extremely rare. There is a bidirectional association between multiple sclerosis and IBD, with a relative risk for comorbidity of 1.54, being 1.53 for the risk of multiple sclerosis in IBD and 1.55 for the risk of IBD in multiple sclerosis patients. Anti-TNF-α therapy is contraindicated in the treatment of patients who have both IBD and multiple sclerosis. Demyelinating disorders can also be a rare complication of anti-TNF-α therapy. Optic neuritis, transverse myelitis, progressive myelopathy, central nervous system infections, epilepsy and encephalopathy are among other uncommon neurological complications. Peripheral nervous system manifestations include peripheral neuropathy, either demyelination and axonal, myasthenia gravis and polymyositis/dermatomyositis and localized forms of myositis., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: To investigate if monopolar (MN) and concentric (CN) electrodes are equivalent for volitional contraction jitter estimation in orbicularis oculi (OO), and to study the effect of selecting a specific high-pass filter., Methods: We studied neuromuscular jitter in OO on both sides in 100 consecutive patients with a clinical diagnosis of ocular myasthenia gravis (MG). We used either MN (50 patients) or CN (50 patients) electrodes in individual patients, according to a randomised protocol, with a 1kH high pass filter on one side and a 3kH filter on the other. Ten or more potential pairs were studied on each side., Results: 48 patients had a definite clinical diagnosis of ocular MG, and 52 of mimicking-disorders, who were analysed as controls. In controls, jitter (MCD) showed a normal distribution independent of the electrode type or filter settings. The mean jitter value and the number of abnormal pairs (>10%) was similar in MN and CN recordings, with both 1 kHz and 3 kHz filters. Sensitivity was 73% for mean jitter and 94% for number of abnormal pairs. Specificity was 100%., Conclusions: The jitter in OO using MN or CN was similar in controls and the diagnostic sensitivity was similar using either electrode in patients with ocular MG. The use of high-pass filters of 1 or 3 kHz did not influence these results., Significance: MN and CN are both suitable for determining volitional jitter in OO., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Atherosclerotic plaque molecular imaging with 18 F-sodium fluoride (NaF) in positron emission tomography with computed tomography (PET-CT) provides potential discrimination between active unstable microcalcification and established dormant calcification. We aimed to study 18 F-NaF atherosclerotic plaque uptake in high cardiovascular (CV) risk participants and its associations with CV risk factors, coronary calcium score and thoracic fat volume., Methods: High CV risk hypertensive individuals from a single centre were prospectively scanned with 18 F-NaF-PET-CT in the coronary, aortic and carotideal arteries. Atherosclerotic plaque 18 F-NaF uptake was expressed as Corrected Uptake per Lesion (CUL): maximum standard uptake value in each vascular territory subtracted by mean blood pool activity., Results: Mean age was 64 years, 56% male and 96% Caucasian (n = 25). Ninety six per cent of the subjects showed 18 F-NaF uptake in the aorta (CUL 0.9 ± 0.3), 40% in the carotid arteries (median CUL 0.0, IQR 0.0-0.7) and 64% in the coronary arteries (0.4, IQR 0.0-0.6). Individuals with ≥ five risk factors (60%) had increased overall 18 F-NaF uptake (1.1 ± 0.3 vs. 0.7 ± 0.3, p < 0.01), which was positively correlated with predicted fatal CV risk - SCORE (r = 0.49, p = 0.01). There was no correlation between 18 F-NaF uptake in the coronary arteries and calcium score (p = 0.87). Thoracic fat was moderately correlated with overall CUL (r = 0.41, p = 0.04)., Conclusions: In a high CV risk group, 18 F-NaF atherosclerotic plaque uptake was related to the burden of CV risk factors and thoracic fat volume, but there was no association between coronary uptake and calcium score., (Copyright © 2017 Elsevier B.V. All rights reserved.)