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Background: Recent randomized trials have shown the benefit of mechanical thrombectomy (MT) also in patients with an established large ischemic core. Aims: The purpose of this study was to define baseline predictors of clinical outcome in patients with large vessel occlusion (LVO) in the anterior circulation and an Alberta Stroke Program Early CT score (ASPECTS) ⩽ 5, undergoing MT. Material and methods: The databases of 16 comprehensive stroke centers were retrospectively screened for patients with LVO and ASPECTS ⩽5 that received MT. Baseline clinical and neuroradiological features, including the differential contribution of all ASPECTS regions to the composite score, were collected. Primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0–2. Statistical analysis used a logistic regression model and random forest algorithm. Results: A total of 408 patients were available for analysis. In multivariate model, among baseline features, lower age (odd ratio (OR) = 0.962, 95% confidence interval (CI) = 0.943–0.982) and lower National Institute of Health Stroke Scale (NIHSS) score (OR = 0.911, 95% CI = 0.862–0.963) were associated with the mRS score 0–2. Involvement of the M2 (OR = 0.398, 95% CI = 0.206–0.770) or M4 (OR = 0.496, 95% CI = 0.260–0.945) ASPECTS regions was associated with an unfavorable outcome. Random forest analysis confirmed that age and baseline NIHSS score are the most important variables influencing clinical outcome, whereas involvement of cortical regions M5, M4, M2, and M1 can have a negative impact. Conclusion: Our retrospective analysis shows that, along with age and baseline clinical impairment, presence of early ischemic changes involving cortical areas has a role in clinical outcome in patients with large ischemic core undergoing MT. Data access statement: The data that support the findings of this study are available upon reasonable request. [ABSTRACT FROM AUTHOR]

Background and purpose: Myopathies are associated with classic signs and symptoms, but also with possible life‐threatening complications that may require assistance in an emergency setting. This phenomenon is understudied in the literature. We aimed to assess the presentation, management, and outcomes of clinical manifestations potentially related to a muscle disorder requiring referral to the adult emergency department (ED) and hospitalization. Methods: Anonymized patient data retrieved using the International Classification of Diseases, Ninth Revision codes related to muscle disorders over 4 years were retrospectively analyzed. Medical reports were evaluated to extract demographic and clinical variables, along with outcomes. Two groups were defined based on the presence (known diagnosis [KD] group) or absence (unknown diagnosis [UD] group) of a diagnosed muscle disorder at arrival. Results: A total of 244 patients were included, 51% of whom were affected by a known myopathy, predominantly limb‐girdle muscular dystrophies and myotonic dystrophies. The main reasons for ED visits in the KD group were respiratory issues, worsening of muscle weakness, and gastrointestinal problems. Heart complications were less prevalent. In the UD group, 27 patients received a new diagnosis of a specific primary muscle disorder after the ED access, mostly an inflammatory myopathy. Death during hospitalization was recorded in 26 patients, with a higher rate in the KD group and in patients affected by mitochondrial and inflammatory myopathies. Sepsis and dyspnea were associated with increased death risk. Conclusions: Respiratory complications are the most common reason for myopathic patients accessing the ED, followed by gastrointestinal issues. Infections are severe threats and, once hospitalized, these patients have relatively high mortality. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy with a wide range of manifestations including retinal vasculopathy. This study aimed to analyse retinal vascular involvement in FSHD patients using fundus photographs and optical coherence tomography-angiography (OCT-A) scans, evaluated through artificial intelligence (AI). Thirty-three patients with a diagnosis of FSHD (mean age 50.4 ± 17.4 years) were retrospectively evaluated and neurological and ophthalmological data were collected. Increased tortuosity of the retinal arteries was qualitatively observed in 77% of the included eyes. The tortuosity index (TI), vessel density (VD), and foveal avascular zone (FAZ) area were calculated by processing OCT-A images through AI. The TI of the superficial capillary plexus (SCP) was increased (p < 0.001), while the TI of the deep capillary plexus (DCP) was decreased in FSHD patients in comparison to controls (p = 0.05). VD scores for both the SCP and the DCP results increased in FSHD patients (p = 0.0001 and p = 0.0004, respectively). With increasing age, VD and the total number of vascular branches showed a decrease (p = 0.008 and p < 0.001, respectively) in the SCP. A moderate correlation between VD and EcoRI fragment length was identified as well (r = 0.35, p = 0.048). For the DCP, a decreased FAZ area was found in FSHD patients in comparison to controls (t (53) = −6.89, p = 0.01). A better understanding of retinal vasculopathy through OCT-A can support some hypotheses on the disease pathogenesis and provide quantitative parameters potentially useful as disease biomarkers. In addition, our study validated the application of a complex toolchain of AI using both ImageJ and Matlab to OCT-A angiograms. [ABSTRACT FROM AUTHOR]

• Muscle imaging can provide different biomarkers for FSHD. • Consensus on the diagnostic usefulness of MRI and its role in patients' stratification. • Consensus on the harmonization and improvement of available quantitative MRI protocols. • Proposal of a shared research agenda between the FSHD CTRN and ETN imaging working groups. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of facioscapulohumeral muscular dystrophy (FSHD) can be challenging in patients not displaying the classical phenotype or with atypical clinical features. Despite the identification by magnetic resonance imaging (MRI) of selective patterns of muscle involvement, their specificity and added diagnostic value are unknown. Methods: We aimed to identify the radiological features more useful to distinguish FSHD from other myopathies and test the diagnostic accuracy of MRI. A retrospective cohort of 295 patients (187 FSHD, 108 non-FSHD) studied by upper and lower-limb muscle MRI was analyzed. Scans were evaluated for the presence of 15 radiological features. A random forest machine learning algorithm was used to identify the most relevant for FSHD diagnosis. Different patterns were created by their combination and diagnostic accuracy of each of them was tested. Results: The combination of trapezius involvement and bilateral subscapularis muscle sparing achieved the best diagnostic accuracy (0.89, 95% Confidence Interval [0.85–0.92]) with 0.90 [0.85–0.94] sensitivity and 0.88 [0.80–0.93] specificity. This pattern correctly identified 91% atypical FSHD patients of our cohort. The combination of trapezius involvement, bilateral subscapularis and iliopsoas sparing and asymmetric involvement of upper and lower-limb muscles was pathognomonic for FSHD, yielding a specificity of 0.99 [0.95–1.00]. Conclusions: We identified MRI patterns that showed a high diagnostic power in promptly discriminating FSHD from other muscle disorders, with comparable performance irrespective of typical or atypical clinical features. Upper girdle in addition to lower-limb muscle imaging should be extensively implemented in the diagnostic workup to support or exclude a diagnosis of FSHD. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Muscle diffusion tensor imaging has not yet been explored in facioscapulohumeral muscular dystrophy (FSHD). We assessed diffusivity parameters in FSHD subjects compared with healthy controls (HCs), with regard to their ability to precede any fat replacement or edema. Methods: Fat fraction (FF), water T2 (wT2), mean, radial, axial diffusivity (MD, RD, AD), and fractional anisotropy (FA) of thigh muscles were calculated in 10 FSHD subjects and 15 HCs. All parameters were compared between FSHD and controls, also exploring their gradient along the main axis of the muscle. Diffusivity parameters were tested in a subgroup analysis as predictors of disease involvement in muscle compartments with different degrees of FF and wT2 and were also correlated with clinical severity scores. Results: We found that MD, RD, and AD were significantly lower in FSHD subjects than in controls, whereas we failed to find a difference for FA. In contrast, we found a significant positive correlation between FF and FA and a negative correlation between MD, RD, and AD and FF. No correlation was found with wT2. In our subgroup analysis we found that muscle compartments with no significant fat replacement or edema (FF < 10% and wT2 < 41 ms) showed a reduced AD and FA compared with controls. Less involved compartments showed different diffusivity parameters than more involved compartments. Discussion: Our exploratory study was able to demonstrate diffusivity parameter abnormalities even in muscles with no significant fat replacement or edema. Larger cohorts are needed to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

Sporadic late-onset nemaline myopathy (SLONM) is a rare acquired myopathy characterized by rapid-onset proximal weakness in late adulthood, and the presence of nemaline bodies on muscle biopsy. In recent years, several therapeutic interventions, including immunomodulating agents and autologous stem cell transplantation, have shown variable degrees of efficacy in different patients, but no consensus has been reached to allow an effective tailoring of treatments in this severe disease. We performed a retrospective evaluation of clinical, pathological, laboratory, muscle MRI, and follow-up data of SLONM patients diagnosed in the period 2010-2015 in our neuromuscular center. Six patients (three males and three females) were identified. Average time elapsed from the onset of symptoms to referral to the neuromuscular specialist was 23.7 months. Monoclonal gammopathy was detectable in five patients. Nemaline bodies were detected in all the patients, and their abundance correlated with clinical severity. Signs of cardiac involvement were present in all the patients to different extents. Muscle MRI showed a preferential involvement of neck extensors, paraspinal, gluteal, hamstring and soleus muscles. All patients were treated with prednisone and repeated courses of intravenous immunoglobulins, and a favorable outcome was reached in five patients. Our experience confirms that SLONM is clinically characterized by subacute proximal and axial muscle weakness. Time to referral was relatively long and should be reduced with increasing awareness of the disease. Muscle MRI could be of help as a diagnostic tool to identify this potentially treatable myopathy. Cardiac evaluation should be warranted in all SLONM patients to detect subclinical heart involvement. [ABSTRACT FROM AUTHOR]

Objective: Therapeutic perspectives have brought attention to the development of instruments to accurately evaluate the degree of pathology in patients with facioscapulohumeral muscular dystrophy. We aimed to analyze the type and extent of muscle involvement on magnetic resonance imaging (MRI) in a large cohort of patients representative of the broad clinical spectrum of this disease.Methods: Pelvic and lower limb muscle MRI scans of 269 symptomatic individuals and 19 nonpenetrant gene carriers were assessed. Comparative analysis of the upper girdle scan in 181 of these subjects was also performed.Results: We found a peculiar susceptibility and resistance of particular muscles. Combined involvement of abdominal and hamstring muscles with iliopsoas sparing is common in facioscapulohumeral muscular dystrophy (67% of the patients). Adductor longus and/or rectus femoris, whose involvement can go clinically undetected, are often typically affected in early disease (69% of patients younger than 45 years). The extent of lesions on lower limb MRI showed a high correlation with overall clinical severity. One-fourth of the nonpenetrant gene carriers showed abnormalities on MRI. Hyperintensities on short-tau inversion recovery sequences, markers of active disease, were found in muscles without signs of fatty replacement in 35% of patients, representing early lesions.Interpretation: Our large-scale cross-sectional data provide preliminary evidence for the usefulness of MRI in clinical trials, and set the baseline for longitudinal studies. Muscle MRI can also be used for distinguishing facioscapulohumeral muscular dystrophy from other myopathies in selected cases. Finally, our results are consistent with a model that configures facioscapulohumeral muscular dystrophy as a "muscle-by-muscle" disease. Ann Neurol 2016;79:854-864. [ABSTRACT FROM AUTHOR]

Introduction: In sporadic inclusion-body myositis (IBM), additional tools are needed to confirm the diagnosis, particularly in clinically atypical or pathologically unproven patients. The aims of this study were to define the pattern of muscle MRI in IBM and to assess its accuracy in differentiating IBM from other myopathies that overlap with it clinically or pathologically.Methods: Blind assessment was done on the scans of 17 definite IBM, 2 possible IBM, and 118 patients with other myopathies.Results: The diagnostic accuracy to detect definite IBM was 95% for the typical pattern (with 100% specificity) and 97% for both typical and consistent patterns (with 97% specificity).Conclusions: Muscle MRI is an accurate tool for diagnostic work-up of suspected IBM patients and may be particularly helpful in patients with early disease or who lack the classical IBM pathology. [ABSTRACT FROM AUTHOR]

Background: In Facioscapulohumeral muscular dystrophy (FSHD), the upper girdle is early involved and often difficult to assess only relying on physical examination. Our aim was to evaluate the pattern and degree of involvement of upper girdle muscles in FSHD compared with other muscle diseases with scapular girdle impairment. Methods: We propose an MRI protocol evaluating neck and upper girdle muscles. One hundred-eight consecutive symptomatic FSHD patients and 45 patients affected by muscular dystrophies and myopathies with prominent upper girdle involvement underwent this protocol. Acquired scans were retrospectively analyzed. Results: The trapezius (100% of the patients) and serratus anterior (85% of the patients) were the most and earliest affected muscles in FSHD, followed by the latissimus dorsi and pectoralis major, whilst spinati and subscapularis (involved in less than 4% of the patients) were consistently spared even in late disease stages. Asymmetry and hyperintensities on short-tau inversion recovery (STIR) sequences were common features, and STIR hyperintensities could also be found in muscles not showing signs of fatty replacement. The overall involvement appears to be disease-specific in FSHD as it significantly differed from that encountered in the other myopathies. Conclusions: The detailed knowledge of single muscle involvement provides useful information for correctly evaluating patients' motor function and to set a baseline for natural history studies. Upper girdle imaging can also be used as an additional tool helpful in supporting the diagnosis of FSHD in unclear situations, and may contribute with hints on the currently largely unknown molecular pathogenesis of this disease. [ABSTRACT FROM AUTHOR]

A 70-year-old male affected by stage two chronic kidney disease underwent left internal carotid stenting for critical stenosis (contrast agent used: iomeprol). A head computed tomography (CT) scan showed cortical hyperdensity due to contrast leakage in the left frontal lobe [Figure 1]a, without signs of vessel occlusion [Figure 1]b. Awareness and identification of CIE is crucial to avoid unnecessary treatment of this usually benign disease.[[5]] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. [Extracted from the article]

Background: Facioscapulohumeral dystrophy (FSHD) is a myopathy characterized by the loss of repressive epigenetic features affecting the D4Z4 locus (4q35). The assessment of DNA methylation at two regions (DUX4-PAS and DR1) of D4Z4 locus proved to be an effective method to detect epigenetic signatures compatible with FSHD. The present study aims at validating the employment of this method into clinical practice and improving the protocol by refining the classification thresholds of 4qA/4qA patients. To this purpose, 218 subjects with clinical suspicion of FSHD collected in 2022–2023 were analyzed. Each participant underwent in parallel the traditional FSHD molecular testing (D4Z4 sizing) and the proposed methylation assay. The results provided by both analyses were compared to evaluate the concordance and calculate the performance metrics of the methylation test. Results: Among the 218 subjects, the 4q variant type distribution was 54% 4qA/4qA, 43% 4qA/4qB and 3% 4qB/4qB. The methylation analysis was performed only on carriers of at least one 4qA allele. After refining the classification threshold, the test reached the following performance metrics: sensitivity = 0.90, specificity = 1.00 and accuracy = 0.93. These results confirmed the effectiveness of the methylation assay in identifying patients with genetic signature compatible with FSHD1 and FSHD2 based on their DUX4-PAS and DR1 profile, respectively. The methylation data were also evaluated with respect to the clinical information. Conclusions: The study confirmed the ability of the method to accurately identify methylation profiles compatible with FSHD genetic signatures considering the 4q genotype. Moreover, the test allows the detection of hypomethylated profiles in asymptomatic patients, suggesting its potential application in identifying preclinical conditions in patients with positive family history and FSHD genetic signatures. Furthermore, the present work emphasizes the importance of interpreting methylation profiles considering the patients' clinical data. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, defined as the loss of skeletal muscle mass, has been associated with a worse functional outcome after stroke. Measurement of temporal muscle thickness (TMT) has been introduced as an easily obtainable surrogate marker to identify patients with sarcopenia. Our study aims to investigate the correlation between pre-stroke sarcopenia, measured by TMT assessment, and functional outcome in patients treated with revascularization procedures for acute ischemic stroke. Methods: We included consecutive adult patients who underwent thrombolysis, endovascular thrombectomy or both for acute ischemic stroke at our Centre from January 2020 to June 2022. Besides collecting baseline clinical and neuroradiological features, TMT was measured on brain computed tomography scans according to a standardized protocol. Modified Rankin Scale (mRS) scores at 3 months represented the main endpoint of functional outcome. Results: A total of 261 patients were available for the analysis. In univariate models, patients with excellent outcomes (mRS = 0–1) were younger, had higher TMT values and lower pre-event disability and stroke severity. In multivariate models higher TMT values resulted independently associated with reduced mortality (Odds Ratio 0.708, 95% Confidence Interval 0.538–0.930, p = 0.013). Age, diabetes, brain bleeding events and stroke severity were found to be predictors of mortality, too. Conclusions: Our retrospective analysis shows that in patients who underwent revascularization treatments for ischemic stroke TMT is as an independent predictor of survival easily obtainable from the baseline CT scan. Further investigation is required to confirm the role of sarcopenia assessment and TMT measurement in the prognostication toolkit of this disease. [ABSTRACT FROM AUTHOR]

The article describes the case of a patient with neuromyelitis optica (NMO) who was diagnosed with tuberculous nephritis in Nigeria. Examinations included cerebrospinal fluid examination (CSF) and a total body computed tomography (CT). Treatments included intravenous methylprednisolone, antitubercular therapy, and immunosuppressive therapy.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4 in skeletal muscle. Detecting DUX4 and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to analyze the protein repertoire of interstitial fluids obtained from 20 muscles in different disease stages classified by magnetic resonance imaging (MRI) and serum samples from 10 FSHD patients. A total of 1156 proteins were identified in the microdialysates by data independent acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles were able to distinguish FSHD patients from controls. Two innate immunity mediators (S100-A8 and A9) and Dermcidin were upregulated in muscles with active disease and selectively present in the sera of FSHD patients. Structural muscle and plasminogen pathway proteins were downregulated. Together with the upstream inhibition of myogenic factors, this suggests defective muscle regeneration and increased fibrosis in early/active FSHD. Our MRI targeted exploratory approach confirmed that inflammatory response has a prominent role, together with impaired muscle regeneration, before clear muscle wasting occurs. We also identified three proteins as tissue and possibly circulating biomarkers in FSHD. [ABSTRACT FROM AUTHOR]

Background: Automated pupillometry (AP) is a handheld, non-invasive tool that is able to assess pupillary light reflex dynamics and is useful for the detection of intracranial hypertension. Limited evidence is available on acute ischemic stroke (AIS) patients. The primary objective was to evaluate the ability of AP to discriminate AIS patients from healthy subjects (HS). Secondly, we aimed to compute a predictive score for AIS diagnosis based on clinical, demographic, and AP variables. Methods: We included 200 consecutive patients admitted to a comprehensive stroke center who underwent AP assessment through NPi-200 (NeurOptics®) within 72 h of stroke onset and 200 HS. The mean values of AP parameters and the absolute differences between the AP parameters of the two eyes were considered in the analyses. Predictors of stroke diagnosis were identified through univariate and multivariate logistic regressions; we then computed a nomogram based on each variable's β coefficient. Finally, we developed a web app capable of displaying the probability of stroke diagnosis based on the predictive algorithm. Results: A high percentage of pupil constriction (CH, p < 0.001), a low constriction velocity (CV, p = 0.002), and high differences between these two parameters (p = 0.036 and p = 0.004, respectively) were independent predictors of AIS. The highest contribution in the predictive score was provided by CH, the Neurological Pupil Index, CV, and CV absolute difference, disclosing the important role of AP in the discrimination of stroke patients. Conclusions: The results of our study suggest that AP parameters, and in particular, those concerning pupillary constriction, may be useful for the early diagnosis of AIS. [ABSTRACT FROM AUTHOR]

The article describes a case of plasmapheresis in Epstein Barr Virus (EBV)-related post-infectious cerebellitis in a previously healthy 19-year-old male evaluated for acute onset of speech disturbances and imbalance following an episode of fever and sore throat. Topics include details of the findings of the patient's neurological examinations, the indications of EBV infections, and the benefits of using plasmapheresis.

Background and purpose: Post‐stroke movement disorders (PMDs) following ischemic lesions of the basal ganglia (BG) are a known entity, but data regarding their incidence are lacking. Ischemic strokes secondary to proximal middle cerebral artery (MCA) occlusion treated with thrombectomy represent a model of selective damage to the BG. The aim of this study was to assess the prevalence and features of movement disorders after selective BG ischemia in patients with successfully reperfused acute ischemic stroke (AIS). Methods: We enrolled 64 consecutive subjects with AIS due to proximal MCA occlusion treated with thrombectomy. Patients were clinically evaluated by a movement disorders specialist for PMDs onset at baseline, and after 6 and 12 months. Results: None of the patients showed an identifiable movement disorder in the subacute phase of the stroke. At 6 and 12 months, respectively, 7/25 (28%) and 7/13 (53.8%) evaluated patients developed PMDs. The clinical spectrum of PMDs encompassed parkinsonism, dystonia and chorea, either isolated or combined. In most patients, symptoms were contralateral to the lesion, although a subset of patients presented with bilateral involvement and prominent axial signs. Conclusion: Post‐stroke movement disorders are not uncommon in long‐term follow‐up of successfully reperfused AIS. Follow‐up conducted by a multidisciplinary team is strongly advisable in patients with selective lesions of the BG after AIS, even if asymptomatic at discharge. [ABSTRACT FROM AUTHOR]

Background: Little evidence is available on the long-term efficacy and safety of edoxaban, mainly due to the recent release date. The primary objective of the study was to evaluate the safety of edoxaban, defined by the incidence of major bleedings. We then aimed to evaluate the incidence of thromboembolic events and the persistence of edoxaban therapy in the long-term. Methods: In this observational cohort study, we included ischemic stroke patients enrolled in a previous study to evaluate the safety and efficacy of long-term edoxaban treatment. Data were collected by a trained investigator through a structured telephone interview. Results: Sixty-three subjects (median age 81.0 (73.5–88.0) years, 38.1% male) were included in the study, with a mean follow-up of 4.4 ± 0.7 years (range: 3.2–5.5 years). Only one patient (1.6%, 0.4%/year) presented a major extracranial bleeding, and none had cerebral hemorrhage. Six thromboembolic events occurred in five patients (7.9%): three recurrent strokes, two transient ischemic attacks, and one myocardial infarction (2.2%/year). Over a follow-up period of more than three years, 13 patients discontinued edoxaban (20.6%). Conclusions: Edoxaban seems to be effective and safe in the long-term. The persistence rate of edoxaban therapy is optimal after more than three years of treatment. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant epigenetic disorder with highly variable muscle involvement and disease progression. Ongoing clinical trials, aimed at counteracting muscle degeneration and disease progression in FSHD patients, increase the need for reliable biomarkers. Muscle magnetic resonance imaging (MRI) studies showed that the appearance of STIR-positive (STIR+) lesions in FSHD muscles represents an initial stage of muscle damage, preceding irreversible adipose changes. Our study aimed to investigate fibrosis, a parameter of muscle degeneration undetectable by MRI, in relation to disease activity and progression of FSHD muscles. We histologically evaluated collagen in FSHD1 patients’ (STIR+ n = 27, STIR− n = 28) and healthy volunteers’ (n = 12) muscles by picrosirius red staining. All patients (n = 55) performed muscle MRI before biopsy, 45 patients also after 1 year and 36 patients also after 2 years. Fat content (T1 signal) and oedema/inflammation (STIR signal) were evaluated at baseline and at 1- and 2-year MRI follow-up. STIR+ muscles showed significantly higher collagen compared to both STIR− (p = 0.001) and healthy muscles (p < 0.0001). STIR− muscles showed a higher collagen content compared to healthy muscles (p = 0.0194). FSHD muscles with a worsening in fatty infiltration during 1- (P = 0.007) and 2-year (P < 0.0001) MRI follow-up showed a collagen content of 3.6- and 3.7-fold higher compared to FSHD muscles with no sign of progression. Moreover, the fibrosis was significantly higher in STIR+ muscles who showed a worsening in fatty infiltration in a timeframe of 2 years compared to both STIR− (P = 0.0006) and STIR+ muscles with no sign of progression (P = 0.02). Fibrosis is a sign of muscle degeneration undetectable at MRI never deeply investigated in FSHD patients. Our data show that 23/27 of STIR+ and 12/28 STIR− muscles have a higher amount of collagen deposition compared to healthy muscles. Fibrosis is higher in FSHD muscles with a worsening in fatty infiltration thus suggesting that its evaluation with innovative non-invasive techniques could be a candidate prognostic biomarker for FSHD, to be used to stratify patients and to evaluate the efficacy of therapeutic treatments. [ABSTRACT FROM AUTHOR]

• Muscle MRI reveals consistent features shared by patients with distal hereditary motor neuropathies that can be helpful for the diagnosis process. • A reticular pattern of fat replacement progressing towards fat islands is the most common finding observed across all patients. • Distal muscles of the lower legs are the most affected, especially the posterior compartment of the legs including soleus and gastrocnemius muscles. • A distal to proximal gradient of fat replacement is frequent in this cohort of patients, suggesting there is a dying-back phenomenon of axon degeneration. • Hyperintensities in STIR signal are common, following a distal to proximal gradient in many cases suggesting that there is an active process of denervation in several patients. Distal motor neuropathies (dHMN) are an heterogenous group of diseases characterized by progressive muscle weakness affecting predominantly the distal muscles of the lower and upper limbs. Our aim was to study the imaging features and pattern of muscle involvement in muscle magnetic resonance imaging (MRI) in dHMN patients of suspected genetic origin (dHMN). We conducted a retrospective study collecting clinical, genetic and muscle imaging data. Muscle MRI included T1-weighted and T2 weighted Short Tau Inversion Recovery images (STIR-T2w) sequences. Muscle replacement by fat was quantified using the Mercuri score. Identification of selective patterns of involvement was performed using hierarchical clustering. Eighty-four patients with diagnosis of dHMN were studied. Fat replacement was predominant in the distal lower leg muscles (82/84 cases), although also affected thigh and pelvis muscles. Asymmetric involvement was present in 29% of patients. The superficial posterior compartment of the leg, including the soleus and gastrocnemius muscles, was the most affected area (77/84). We observed a reticular pattern of fatty replacement progressing towards what is commonly known as "muscle islands" in 79.8%. Hyperintensities in STIR-T2w were observed in 78.6% patients mainly in distal leg muscles. Besides features common to all individuals, we identified and describe a pattern of muscle fat replacement characteristic of BICD2, HSPB1 and DYNC1H1 patients. We conclude that muscle MRI of patients with suspected dHMN reveals common features helpful in diagnosis process. [ABSTRACT FROM AUTHOR]

The study describes a protocol for methylation analysis integrated with Machine Learning (ML) algorithms developed to classify Facio-Scapulo-Humeral Dystrophy (FSHD) subjects. The DNA methylation levels of two D4Z4 regions (DR1 and DUX4-PAS) were assessed by an in-house protocol based on bisulfite sequencing and capillary electrophoresis, followed by statistical and ML analyses. The study involved two independent cohorts, namely a training group of 133 patients with clinical signs of FSHD and 150 healthy controls (CTRL) and a testing set of 27 FSHD patients and 25 CTRL. As expected, FSHD patients showed significantly reduced methylation levels compared to CTRL. We utilized single CpG sites to develop a ML pipeline able to discriminate FSHD subjects. The model identified four CpGs sites as the most relevant for the discrimination of FSHD subjects and showed high metrics values (accuracy: 0.94, sensitivity: 0.93, specificity: 0.96). Two additional models were developed to differentiate patients with lower D4Z4 size and patients who might carry pathogenic variants in FSHD genes, respectively. Overall, the present model enables an accurate classification of FSHD patients, providing additional evidence for DNA methylation as a powerful disease biomarker that could be employed for prioritizing subjects to be tested for FSHD. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether and how COVID-19 vaccination may affect the outcome of patients with acute ischemic stroke (AIS). We investigated this potential association in a retrospective study by comparing previously vaccinated (VAX) versus unvaccinated (NoVAX) stroke patients. Methods: We collected clinical reports for all consecutive AIS patients admitted to our hospital and evaluated the outcome predictors in VAX and NoVAX groups. Adjustments were made for possible confounders in multivariable logistic regression analysis, and adjusted hazard ratios were calculated. Results: A total of 466 AIS patients (287 VAX and 179 NoVAX) were included in this study. The NIHSS score at discharge and mRS score at a 3-month follow-up visit were significantly lower in VAX patients compared to NoVAX patients (p < 0.001). Good outcomes (mRS 0–2) were significantly associated with COVID-19 vaccination before AIS (adjusted hazard ratio, 0.400 [95% CI = 0.216–0.741]). Conclusions: The observation that COVID-19 vaccination can influence the outcome of AIS provides support for further studies investigating the role of immunity in ischemic brain damage. [ABSTRACT FROM AUTHOR]

• Deep learning technique for fast MR parameters mapping of several neuromuscular disorders. • We developed a physics informed neural NetwOrk Myo-DINO for MR parameters mapping enhancing explainability of the learning process. • Myo-DINO accurately reconstructed fat Fraction, water T2 and B1 parameters maps. • Myo-DINO allowed for accelerated and effective parameters prediction of several lower limbs muscles. Magnetic Resonance (MR) parameters mapping in muscle Magnetic Resonance Imaging (mMRI) is predominantly performed using pattern recognition-based algorithms, which are characterised by high computational costs and scalability issues in the context of multi-parametric mapping. Deep Learning (DL) has been demonstrated to be a robust and efficient method for rapid MR parameters mapping. However, its application in mMRI domain to investigate Neuromuscular Disorders (NMDs) has not yet been explored. In addition, data-driven DL models suffered in interpretation and explainability of the learning process. We developed a Physics Informed Neural Network called Myo-Regressor Deep Informed Neural NetwOrk (Myo-DINO) for efficient and explainable Fat Fraction (FF), water-T 2 (wT 2) and B1 mapping from a cohort of NMDs.A total of 2165 slices (232 subjects) from Multi-Echo Spin Echo (MESE) images were selected as the input dataset for which FF, wT 2 ,B1 ground truth maps were computed using the MyoQMRI toolbox. This toolbox exploits the Extended Phase Graph (EPG) theory with a two-component model (water and fat signal) and slice profile to simulate the signal evolution in the MESE framework. A customized U-Net architecture was implemented as the Myo-DINO architecture. The squared L 2 norm loss was complemented by two distinct physics models to define two 'Physics-Informed' loss functions: Cycling Loss 1 embedded a mono-exponential model to describe the relaxation of water protons, while Cycling Loss 2 incorporated the EPG theory with slice profile to model the magnetization dephasing under the effect of gradients and RF pulses. The Myo-DINO was trained with the hyperparameter value of the 'Physics-Informed' component held constant, i.e. λ model = 1, while different hyperparameter values (λ cnn) were applied to the squared L 2 norm component in both the cycling loss. In particular, hard (λ cnn =10), normal (λ cnn =1) and self-supervised (λ cnn =0) constraints were applied to gradually decrease the impact of the squared L 2 norm component on the 'Physics Informed' term during the Myo-DINO training process. Myo-DINO achieved higher performance with Cycling Loss 2 for FF, wT 2 and B1 prediction. In particular, high reconstruction similarity and quality (Structural Similarity Index > 0.92, Peak Signal to Noise ratio > 30.0 db) and small reconstruction error (Normalized Root Mean Squared Error < 0.038) to the reference maps were shown with self-supervised weighting of the Cycling Loss 2. In addition muscle-wise FF, wT 2 and B1 predicted values showed good agreement with the reference values. The Myo-DINO has been demonstrated to be a robust and efficient workflow for MR parameters mapping in the context of mMRI. This provides preliminary evidence that it can be an effective alternative to the reference post-processing algorithm. In addition, our results demonstrate that Cycling Loss 2, which incorporates the Extended Phase Graph (EPG) model, provides the most robust and relevant physical constraints for Myo-DINO in this multi-parameter regression task. The use of Cycling Loss 2 with self-supervised constraint improved the explainability of the learning process because the network acquired domain knowledge solely in accordance with the assumptions of the EPG model. [ABSTRACT FROM AUTHOR]

X-linked myotubular myopathy (XLMTM) is a severe form of centronuclear myopathy, characterized by generalized weakness and respiratory insufficiency, associated with pathogenic variants in the MTM1 gene. NGS targeted sequencing on the DNA of a three-month-old child affected by XLMTM identified the novel hemizygous MTM1 c.1261-5T>G intronic variant, which interferes with the normal splicing process, generating two different abnormal transcripts simultaneously expressed in the patient's muscular cells. The first aberrant transcript, induced by the activation of a cryptic splice site in intron 11, includes four intronic nucleotides upstream of exon 12, resulting in a shift in the transcript reading frame and introducing a new premature stop codon in the catalytic domain of the protein (p.Arg421SerfsTer7). The second aberrant MTM1 transcript, due to the lack of recognition of the 3′ acceptor splice site of intron 11 from the spliceosome complex, leads to the complete skipping of exon 12. We expanded the genotypic spectrum of XLMTM underlying the importance of intron–exons boundaries sequencing in male patients affected by XLMTM. [ABSTRACT FROM AUTHOR]

Tubular aggregate myopathy is a genetically heterogeneous disease characterized by tubular aggregates as the hallmark on muscle biopsy. Mutations in STIM1 have recently been identified as one genetic cause in a number of tubular aggregate myopathy cases. To characterize the pattern of muscle involvement in this disease, upper and lower girdles and lower limbs were imaged in five patients with mutations in STIM1 , and the scans were compared with two patients with tubular aggregate myopathy not caused by mutations in STIM1 . A common pattern of involvement was found in STIM1 -mutated patients, although with variable extent and severity of lesions. In the upper girdle, the subscapularis muscle was invariably affected. In the lower limbs, all the patients showed a consistent involvement of the flexor hallucis longus, which is very rarely affected in other muscle diseases, and a diffuse involvement of thigh and posterior leg with sparing of gracilis, tibialis anterior and, to a lesser extent, short head of biceps femoris. Mutations in STIM1 are associated with a homogeneous involvement on imaging despite variable clinical features. Muscle imaging can be useful in identifying STIM1 -mutated patients especially among other forms of tubular aggregate myopathy. [ABSTRACT FROM AUTHOR]

Quantitative muscle MRI (water-T2 and fat mapping) is being increasingly used to assess disease involvement in muscle disorders, while imaging techniques for assessment of the dynamic and elastic muscle properties have not yet been translated into clinics. In this exploratory study, we quantitatively characterized muscle deformation (strain) in patients affected by facioscapulohumeral muscular dystrophy (FSHD), a prevalent muscular dystrophy, by applying dynamic MRI synchronized with neuromuscular electrical stimulation (NMES). We evaluated the quadriceps muscles in 34 ambulatory patients and 13 healthy controls, at 6-to 12-month time intervals. While a subgroup of patients behaved similarly to controls, for another subgroup the median strain decreased over time (approximately 57% over 1.5 years). Dynamic MRI parameters did not correlate with quantitative MRI. Our results suggest that the evaluation of muscle contraction by NMES-MRI is feasible and could potentially be used to explore the elastic properties and monitor muscle involvement in FSHD and other neuromuscular disorders. [ABSTRACT FROM AUTHOR]

Background and purpose: Portable and wearable devices can monitor a number of physical performances and lately have been applied to patients with neuromuscular disorders (NMDs). Methods: We performed a systematic search of literature databases following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) principles, including all studies reporting the use of technological devices for motor function assessment in NMDs from 2000 to 2021. We also summarized the evidence on measurement properties (validity, reliability, responsiveness) of the analyzed technological outcome measures. Results: One hundred studies fulfilled the selection criteria, most of them published in the past 10 years. We defined four categories that gathered similar technologies: gait analysis tools, for clinical assessment of pace and posture; continuous monitoring of physical activity with inertial sensors, which allow "unsupervised" activity assessment; upper limb evaluation tools, including Kinect‐based outcome measures to assess the reachable workspace; and new muscle strength assessment tools, such as Myotools. Inertial sensors have the evident advantage of being applied in the "in‐home" setting, which has become especially appealing during the COVID‐19 pandemic, although poor evidence from psychometric property assessment and results of the analyzed studies may limit their research application. Both Kinect‐based outcome measures and Myotools have already been validated in multicenter studies and different NMDs, showing excellent characteristics for application in clinical trials. Conclusions: This overview is intended to raise awareness on the potential of the different technology outcome measures in the neuromuscular field and to be an informative source for the design of future clinical trials, particularly in the era of telemedicine. [ABSTRACT FROM AUTHOR]

Introduction: Mutations in the gene that encodes filamin C, FLNC, represent a rare cause of a distinctive type of myofibrillar myopathy (MFM). Methods: We investigated an Italian patient by means of muscle biopsy, muscle and brain imaging and molecular analysis of MFM genes. Results: The patient harbored a novel 7256C>T, p.Thr2419Met mutation in exon 44 of FLNC. Clinical, pathological and muscle MRI findings were similar to the previously described filaminopathy cases. This patient had, in addition, cerebellar ataxia with atrophy of cerebellum and vermis evident on brain MRI scan. Extensive screening failed to establish a cause of cerebellar atrophy. Conclusions: We report an Italian filaminopathy patient, with a novel mutation in a highly conserved region. This case raises the possibility that the disease spectrum caused by FLNC may include cerebellar dysfunction. Muscle Nerve 275-282, 2012 [ABSTRACT FROM AUTHOR]

GNE myopathy (MIM 600737) is an autosomal recessive muscle disease caused by mutations in the UDP- N-acetylglucosamine 2-epimerase/ N-acetylmannosamine kinase ( GNE) gene. Besides the typical phenotype, characterized by the initial involvement of the distal leg muscles that eventually spreads proximally with sparing of the quadriceps, uncommon presentations with a non-canonical clinical phenotype, unusual muscle biopsy findings or both are increasingly recognized. The aim of our study was to characterize the imaging pattern of pelvic and lower limb muscles in GNE myopathy, thus providing additional diagnostic clues useful in the identification of patients with atypical features. We retrospectively evaluated muscle MRI and CT scans of a cohort of 13 patients heterogeneous for GNE mutations and degree of clinical severity. We found that severe involvement of the biceps femoris short head and, to a lesser extent, of the gluteus minimus, tibialis anterior, extensor hallucis and digitorum longus, soleus and gastrocnemius medialis was consistently present even in patients with early or atypical disease. The vastus lateralis, not the entire quadriceps, was the only muscle spared in advanced stages, while the rectus femoris, vastus intermedius and medialis showed variable signs of fatty replacement. Younger patients showed hyperintensities on T2-weighted sequences in muscles with a normal or, more often, abnormal T1-weighted signal. Our results define a pattern of muscle involvement that appears peculiar to GNE myopathy. Although these findings need to be further validated in a larger cohort, we believe that the recognition of this pattern may be instrumental in the initial clinical assessment of patients with possible GNE myopathy. [ABSTRACT FROM AUTHOR]

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease. Methods: Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense). Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed. Results: Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions. Conclusions: At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may contribute to the sequential bursts of muscle degeneration that involve individual muscles in an asynchronous manner in this disease. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a case study of an 84-years-old male who was diagnosed with glycogen storage disease type XV, a form of polyglucosan body myopathy.

Introduction: The COVID-19 outbreak highly impacted the acute ischemic stroke care management. The primary end point of the study was to evaluate the impact of the COVID-19 outbreak and the following lockdown measures on our hub-and-spoke network; the secondary end point was to evaluate if the impact of the COVID-19 outbreak was different in hub-and-spoke centers. Methods: This was a retrospective multicenter observational study conducted at the Stroke Units of Policlinico Gemelli, Ospedale San Filippo Neri, Ospedale di Belcolle, and Ospedale San Camillo de Lellis. We collected clinical reports of all consecutive patients admitted with diagnosis of acute ischemic stroke or transient ischemic attack (TIA) during the phase 1 of the lockdown period (11 March 2020–4 May 2020). As controls, we used all consecutive patients admitted for acute ischemic stroke or TIA in the same period of the previous year. Results: A total of 156 and 142 clinical reports were collected in 2019 and 2020, respectively. During the COVID-19 outbreak, we observed a reduction of number of thrombolysis, a reduction of the length of hospitalization, and an increase of pneumonia. Regarding performance indicators, we observed an increase in onset-to-door time and in door-to-groin time. We did not observe any statistically significant interaction between year (2019 vs 2020) and facility of admission (hub vs spoke) on all variables analyzed. Discussion: Our observational study, involving hub-and-spoke stroke network of a wide regional area, indicates that the COVID-19 outbreak impacted on the acute stroke management. This impact was equally observed in hub as well as in spoke centers. [ABSTRACT FROM AUTHOR]

During the last decade, multiple clinical trials for Duchenne muscular dystrophy (DMD) have focused on the induction of dystrophin expression using different strategies. Many of these trials have reported a clear increase in dystrophin protein following treatment. However, the low levels of the induced dystrophin protein have raised questions on its functionality. In our present study, using an unbiased, high-throughput digital image analysis platform, we assessed markers of regeneration and levels of dystrophin associated protein via immunofluorescent analysis of whole muscle sections in 25 DMD boys who received 48-weeks treatment with exon 53 skipping morpholino antisense oligonucleotide (PMO) golodirsen. We demonstrate that the de novo dystrophin induced by exon skipping with PMO golodirsen is capable of conferring a histological benefit in treated patients with an increase in dystrophin associated proteins at the dystrophin positive regions of the sarcolemma in post-treatment biopsies. Although 48 weeks treatment with golodirsen did not result in a significant change in the levels of fetal/developmental myosins for the entire cohort, there was a significant negative correlation between the amount of dystrophin and levels of regeneration observed in different biopsy samples. Our results provide, for the first time, evidence of functionality of induced dystrophin following successful therapeutic intervention in the human. [ABSTRACT FROM AUTHOR]

• αB-crystallinopathy is a rare myofibrillar myopathy with heterogeneous clinical features. • Reports of muscle imaging in αB-crystallinopathy are scarce. • We present unique MRI findings of severe paraspinal involvement and sparing of lower leg. • Predominant axial weakness may be a presentation of αB-crystallinopathy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of the lockdown measures, consequent to the outbreak of COVID-19 pandemic, on the quality of pre-hospital and in-hospital care of patients with acute ischemic stroke. Methods: This is an observational cohort study. Data sources were the clinical reports of patients admitted during the first month of lockdown and discharged with a confirmed diagnosis of stroke or TIA. Data were collected in the interval ranging from March 11th to April 11th 2020. As controls, we evaluated the clinical reports of patients with stroke or TIA admitted in the same period of 2019. Results: The clinical reports of patients eligible for the study were 52 in 2020 (71.6 ± 12.2 years) and 41 in 2019 (73.7 ± 13.1 years). During the lockdown, we observed a significant increase in onset-to-door time (median = 387 vs 161 min, p = 0.001), a significant reduction of the total number of thrombolysis (7 vs 13, p = 0.033), a non-significant increase of thrombectomy (15 vs 9, p = 0.451), and a significant increase in door-to-groin time (median = 120 vs 93 min, p = 0.048). No relevant difference was observed between 2019 and 2020 in the total number of patients admitted. Conclusions: Due to the COVID-19 pandemic and lockdown measures, the stroke care pathway changed, involving both pre-hospital and in-hospital performances. [ABSTRACT FROM AUTHOR]

Background: Limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A) is a progressive myopathy caused by deficiency of calpain 3, a calcium-dependent cysteine protease of skeletal muscle, and it represents the most frequent type of LGMD worldwide. In the last few years, muscle magnetic resonance imaging (MRI) has been proposed as a tool for identifying patterns of muscular involvement in genetic disorders and as a biomarker of disease progression in muscle diseases. In this study, 57 molecularly confirmed LGMDR1 patients from a European cohort (age range 7–78 years) underwent muscle MRI and a global evaluation of functional status (Gardner-Medwin and Walton score and ability to raise the arms). Results: We confirmed a specific pattern of fatty substitution involving predominantly the hip adductors and hamstrings in lower limbs. Spine extensors were more severely affected than spine rotators, in agreement with higher incidence of lordosis than scoliosis in LGMDR1. Hierarchical clustering of lower limb MRI scores showed that involvement of anterior thigh muscles discriminates between classes of disease progression. Severity of muscle fatty substitution was significantly correlated with CAPN3 mutations: in particular, patients with no or one "null" alleles showed a milder involvement, compared to patients with two null alleles (i.e., predicting absence of calpain-3 protein). Expectedly, fat infiltration scores strongly correlated with functional measures. The "pseudocollagen" sign (central areas of sparing in some muscle) was associated with longer and more severe disease course. Conclusions: We conclude that skeletal muscle MRI represents a useful tool in the diagnostic workup and clinical management of LGMDR1. [ABSTRACT FROM AUTHOR]

Stroke, Anton syndrome, MRI, Basilar artery Keywords: Stroke; Anton syndrome; MRI; Basilar artery EN Stroke Anton syndrome MRI Basilar artery 1119 1120 2 02/15/23 20230301 NES 230301 An 83-year-oldQuery man with a history of hypertension and dyslipidemia presented with visual deficits and dysarthria. Head computed tomography angiography showed a stenosis of the middle third of the basilar artery (panel C) Prolonged electrocardiographic monitoring and transthoracic echocardiography were unremarkable. [Extracted from the article]

Nemaline myopathy (NM) is a skeletal muscle disorder caused by mutations in genes that are generally involved in muscle contraction, in particular those related to the structure and/or regulation of the thin filament. Many pathogenic aspects of this disease remain largely unclear. Here, we report novel pathological defects in skeletal muscle fibres of mouse models and patients with NM: irregular spacing and morphology of nuclei; disrupted nuclear envelope; altered chromatin arrangement; and disorganisation of the cortical cytoskeleton. Impairments in contractility are the primary cause of these nuclear defects. We also establish the role of microtubule organisation in determining nuclear morphology, a phenomenon which is likely to contribute to nuclear alterations in this disease. Our results overlap with findings in diseases caused directly by mutations in nuclear envelope or cytoskeletal proteins. Given the important role of nuclear shape and envelope in regulating gene expression, and the cytoskeleton in maintaining muscle fibre integrity, our findings are likely to explain some of the hallmarks of NM, including contractile filament disarray, altered mechanical properties and broad transcriptional alterations. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 2 (DM2) is an autosomal dominant muscular dystrophy caused by the expansion of an intronic tetranucleotide CCTG repeat in CNBP on chromosome 3. As DM1, DM2 is a multisystem disorder affecting, beside the skeletal muscle, various other tissues, including peripheral nerves. Indeed, a subclinical involvement of peripheral nervous system has been described in several cohorts of DM2 patients, whereas DM2 patients manifesting clinical signs and/or symptoms of neuropathy have been only rarely reported. Here, we describe 2 related DM2 patients both of whom displayed an atypical disease onset characterized by dysautonomic symptoms, possibly secondary to peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Introduction: Limb girdle muscular dystrophies (LGMDs) are characterized by high molecular heterogeneity, clinical overlap, and a paucity of specific biomarkers. Their molecular definition is fundamental for prognostic and therapeutic purposes.Methods: We created an Italian LGMD registry that included 370 molecularly defined patients. We reviewed detailed retrospective and prospective data and compared each LGMD subtype for differential diagnosis purposes.Results: LGMD types 2A and 2B are the most frequent forms in Italy. The ages at disease onset, clinical progression, and cardiac and respiratory involvement can vary greatly between each LGMD subtype. In a set of extensively studied patients, targeted next-generation sequencing (NGS) identified mutations in 36.5% of cases.Conclusion: Detailed clinical characterization combined with muscle tissue analysis is fundamental to guide differential diagnosis and to address molecular tests. NGS is useful for diagnosing forms without specific biomarkers, although, at least in our study cohort, several LGMD disease mechanisms remain to be identified. Muscle Nerve 55: 55-68, 2017. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to evaluate pelvis and lower limb muscle MRI scans of 46 patients affected by Becker muscular dystrophy (BMD), subdivided according to disease severity, ranging from clinically asymptomatic patients to patients who had lost ambulation. We found a distinct pattern on muscle imaging characterized by prominent involvement of the gluteus maximus and medius, adductor magnus, biceps femoris long head, semimembranosus and vasti. This pattern was consistent in all the 25 symptomatic patients. Milder changes in the same muscles were found in 13 of the 21 asymptomatic cases. The other 8 asymptomatic patients had a normal scan. The severity of muscle involvement was significantly correlated with age. Our results suggest that a distinct pattern of muscle involvement can be detected in BMD. The early identification of muscle changes in a proportion of asymptomatic patients may be useful as an additional tool in the diagnostic workup. [Copyright &y& Elsevier]

Abstract: Laing distal myopathy is an autosomal dominant disease due to mutations in the gene encoding for the human slow-β myosin heavy chain, MYH7. Most reports describe it as a mild, early onset myopathy with involvement usually restricted to foot extensors, hand finger extensors and neck flexors, and unspecific findings on muscle biopsy. We identified the first two Italian families with Laing distal myopathy, harboring two novel mutations in the MYH7 gene and performed clinical, neurophysiological, pathological, muscle MRI and cardiological investigations on affected members from the two families. Subjects from one family presented a moderate-severe phenotype, with proximal together with distal involvement and even loss of ambulation at advanced age. One patient displayed atypical muscle biopsy findings including cytoplasmic bodies and myofibrillar myopathy-like features. Affected members from the second family shared a very mild phenotype, with weakness largely limited to long toe and foot extensors and/or late onset. No patient showed any sign of heart involvement. Our study significantly broadens the clinical and pathological spectrum of Laing distal myopathy. We suggest that MYH7 screening should be considered in undiagnosed late-onset distal myopathy or cytoplasmic body myopathy patients. [Copyright &y& Elsevier]

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited disease, and although strongly suggested, a contribution of inflammation to its pathogenesis has never been demonstrated. In FSHD patients, we found by immunohistochemistry inflammatory infiltrates mainly composed by CD8 T cells in muscles showing hyperintensity features on T2-weighted short tau inversion recovery magnetic resonance imaging (T2-STIR-MRI) sequences. Therefore, we evaluated the presence of circulating activated immune cells and the production of cytokines in patients with or without muscles showing hyperintensity features on T2-STIR-MRI sequences and from controls. FSHD patients displaying hyperintensity features in one or more muscles showed higher CD8pSTAT1, CD8T-bet T cells and CD14pSTAT1, CD14T-bet cells percentages and IL12p40, IFNγ and TNFα levels than patients without muscles displaying hyperintense features and controls. Moreover, the percentages of CD8pSTAT1, CD8T-bet and CD14pSTAT1 cells correlated with the proportion of muscles displaying hyperintensity features at T2-STIR sequences. These data indicate that circulating activated immune cells, mainly CD8 T cells, may favour FSHD progression by promoting active phases of muscle inflammation. [ABSTRACT FROM AUTHOR]