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Background and purpose: Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort. Methods: The study employed two distinct methods. MDC was calculated using distribution‐based approaches to consider standard error of measurement and effect size change in a population of 321 patients (176 SMA II and 145 SMA III), allowing for stratification based on age and function. MCID was assessed using anchor‐based methods (receiver operating characteristic [ROC] curve analysis and standard error) on 76 patients (52 SMA II and 24 SMA III) for whom the 12‐month HFMSE could be anchored to a caregiver‐reported clinical perception questionnaire. Results: With both approaches, SMA type II and type III patients had different profiles. The MCID, using ROC analysis, identified optimal cutoff points of −2 for type II and −4 for type III patients, whereas using the standard error we found the optimal cutoff points to be 1.5 for improvement and −3.2 for deterioration. Furthermore, distribution‐based methods uncovered varying values across age and functional status subgroups within each SMA type. Conclusions: These results emphasize that the interpretation of a single MCID or MDC value obtained in large cohorts with different functional status needs to be made with caution, especially when these may be used to assess possible responses to new therapies. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Nusinersen intrathecal administration can be challenging in spinal muscular atrophy (SMA) adults. We aimed to determine if the ultrasound (US)‐assistance reduces the number of needle attempts and needle redirections needed for intrathecal drug administration and its impact on the procedure time, the incidence of adverse events (AEs), and patient satisfaction in these patients. Methods: Fifty‐eight patients aged 18 years and older scheduled for intrathecal nusinersen injection were enrolled and randomized (1:1 ratio) into Group 1 (nusinersen infusion with US‐assisted technique) or Group 2 (nusinersen infusion with landmark‐based technique). The number of attempts, number of redirections, periprocedural time, AEs and patient satisfaction were reported. Continuous variables were compared with the Student t‐test or Wilcoxon rank sum test. Categorical variables were evaluated with the Chi‐square test or Fisher's exact test in case of expected frequencies <5. The p‐values <.05 were considered statistically significant. Results: There were no statistical differences in the number of attempts, AEs, or patient satisfaction between the two groups. The number of needle redirections was significantly lower in the ultrasound group versus landmark‐based group (p <.05) in both the overall group of patients and in the subgroup with difficult spines. The periprocedural time was about 40 seconds longer in US‐group versus landmark‐based group (p <.05). Discussion: In SMA adults, US assistance reduces the number of needle redirections needed for intrathecal drug administration. These results suggest that the US assistance may be advantageous for nusinersen therapy to reduce the therapeutic burden of intrathecal infusion. [ABSTRACT FROM AUTHOR]

Background: The Pediatric Eating Assessment Tool (PEDI‐EAT‐10) is a reliable and valid tool for rapid identification of dysphagia in patients aged 18 months to 18 years. Aims: To translate and adapt the PEDI‐EAT‐10 into the Italian language and evaluate its validity and reliability. Methods & Procedures: The translation and cross‐cultural adaptation of the tool consisted of five stages: initial translation, synthesis of the translations, back translation, expert committee evaluation and test of the prefinal version. The internal consistency of the translated tool was analysed in a clinical group composed of 200 patients with special healthcare needs aged between 18 months and 18 years. They were consecutively enrolled at the Rare Disease Unit, Paediatrics Department, Fondazione Policlinico Agostino Gemelli‐IRCCS, Rome. For test–retest reliability, 50 caregivers filled in the PEDI‐EAT‐10 questionnaire for a second time after a 2‐week period. Construct validity was established by comparing data obtained from patients with data from healthy participants (n = 200). The study was approved by the local ethics committee. Outcomes & Results: Psychometric data obtained from patients (104 M; mean age = 8.08 ± 4.85 years; median age = 7 years) showed satisfactory internal consistency (Cronbach's α = 0.89) and test–retest reliability (Pearson r = 0.99; Spearman r = 0.96). A total of 30% of children were classified as having a high risk of penetration/aspiration. The Italian PEDI‐EAT‐10 mean total score of the clinical group was significantly different from that resulting from healthy participants. Conclusions & Implications: The PEDI‐EAT‐10 was successfully translated into Italian, validated and found to be a reliable one‐page rapid screening tool to identify dysphagia in children and adolescents with special needs. What this paper adds: What is already known on the subject: The PEDI‐EAT‐10 is a valid and reliable quick discriminative paediatric tool for identifying penetration/aspiration risks. What this paper adds to the existing knowledge: In the present study we successfully translated and adapted the PEDI‐EAT‐10 into the Italian language. What are the potential or actual clinical implications of this work?: This translation and adaptation increase access to valid feeding and swallowing assessment for children of Italian‐speaking families. In addition, the I‐PEDI‐EAT‐10 can suggest further assessment of patients' swallowing abilities. [ABSTRACT FROM AUTHOR]

Background: We report the 4‐year follow‐up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number. Methods: The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE‐II). Results: Forty‐eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE‐II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2–4 years, 5–11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE‐2 increased significantly in patients younger than 2 years at treatment. In a mixed‐model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not. Conclusions: Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time. [ABSTRACT FROM AUTHOR]

Background: Intrathecal nusinersen administration, a fundamental step in the treatment of spinal muscular atrophy, is challenging in children. Aims: This retrospective monocentric analysis of prospectively collected data evaluated the feasibility of needleless general anesthesia exclusively with sevoflurane, without imaging guidance, for children undergoing nusinersen administration in a 24‐month period. Methods: Clinical data included demographics, type of spinal muscular atrophy, presence and severity of scoliosis. Primary outcome was defined by the number of predefined sentinel adverse events related to anesthesia. Secondary outcomes were assessed by duration of the procedure, number of lumbar puncture attempts, and number of failures. Other measures included number and type of moderate, minor and minimal adverse events, as well as number and type of puncture‐related adverse events. Results: 116 patients (mean age: 8.7 (SD 6.9) years; with scoliosis: 49.1%) underwent 250 lumbar punctures; two cases of prolonged desaturation, considered as sentinel adverse events, (0.8%) were recorded during anesthesia (primary outcome). None of the patients underwent orotracheal intubation nor required an unplanned admission in the Pediatric Intensive Care Unit. No patient required an unplanned or prolonged hospitalization after the procedure. Mean number of puncture attempts was 1.6 (SD 1.3), and mean duration of the procedure was 14.1 (SD 8.3) minutes. No failure in the drug administration occurred (secondary outcomes). Conclusion: In this single‐center experience, needleless general anesthesia with inhaled sevoflurane without imaging guidance has been shown to be feasible for children with spinal muscular atrophy undergoing lumbar puncture for nusinersen administration. [ABSTRACT FROM AUTHOR]

The study reports real world data in type 2 and 3 SMA patients treated for at least 2 years with nusinersen. Increase in motor function was observed after 12 months and during the second year. The magnitude of change was variable across age and functional subgroup, with the largest changes observed in young patients with higher function at baseline. When compared to natural history data, the difference between study cohort and untreated patients swas significant on both Hammersmith Functional Motor Scale and Revised Upper Limb Module both at 12 months and at 24 months. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Intrathecal nusinersen administration can be challenging in certain adult spinal muscular atrophy (SMA) patients with difficult spinal anatomy who require imaging techniques (fluoroscopy or computed tomography scans) or invasive approaches (catheter placement, laminotomy) to identify the intrathecal space. We used ultrasound (US) assistance to access the lumbar intrathecal space in patients with SMA who experienced previous difficulties or failures with intrathecal dosing. Methods: Eighteen adult patients with difficult spines were enrolled. We used US assistance, and we recorded the successful administrations, number of attempts, procedure times, and "patient satisfaction." Results: There were 57 consecutive successful nusinersen spinal administrations in all patients enrolled. In 50% of patients, two or fewer attempts were needed to obtain a successful administration, with four or fewer attempts in 83.3%; only three patients reported more than four attempts because of both severe scoliosis and severe spine rotation (two patients) and obesity (one patient). The mean procedure time was 11.8 min (range, 1.7–28.9). Patient satisfaction was 4.97/5 (range, 4–5; median, 5) on Likert scale at 5 min and at 72 h. No major adverse events were reported, and two post dural puncture headaches were managed with medical therapy and with complete resolution within 72 h. Discussion: US assistance seems to be a valid option among treatment choices for intrathecal nusinersen administration in patients with difficult spine. The absence of radiation exposure and the lack of need for intravenous sedation or general anesthesia are additional potential advantages to US assisted administration. [ABSTRACT FROM AUTHOR]

Introduction: The Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) have been widely used in natural history studies and clinical trials. Our aim was to establish how the scales relate to each other at different age points in spinal muscular atrophy (SMA) type 2 and 3, and to describe their coherence over 12 mo. Methods: The study was performed by cross‐sectional and longitudinal reanalysis of previously published natural history data. The longitudinal analysis of the 12‐mo changes also included the analysis of concordance between scales with changes grouped as stable (±2 points), improved (>+2) or declined (>−2). Results: Three hundred sixty‐four patients were included in the cross‐sectional analysis, showing different trends in score and point of slope change for the two scales. For type 2, the point of slope change was 4.1 y for the HFMSE and 5.8 for the RULM, while for type 3, it was 6 y for the HFMSE and 7.3 for the RULM. One‐hundred‐twenty‐one patients had at least two assessments at 12 mo. Full concordance was found in 57.3% of the assessments, and in 40.4% one scale remained stable and the other changed. Each scale appeared to be more sensitive to specific age or functional subgroups. Discussion: The two scales, when used in combination, may increase the sensitivity to detect clinically meaningful changes in motor function in patients with SMA types 2 and 3. [ABSTRACT FROM AUTHOR]

Objective: We report longitudinal data from 144 type III SMA pediatric and adult patients treated with nusinersen as part of an international effort. Methods: Patients were assessed using Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and 6‐Minute Walk Test (6MWT) with a mean follow‐up of 1.83 years after nusinersen treatment. Results: Over 75% of the 144 patients had a 12‐month follow‐up. There was an increase in the mean scores from baseline to 12 months on both HFMSE (1.18 points, p = 0.004) and RULM scores (0.58 points, p = 0.014) but not on the 6MWT (mean difference = 6.65 m, p = 0.33). When the 12‐month HFMSE changes in the treated cohort were compared to an external cohort of untreated patients, in all untreated patients older than 7 years, the mean changes were always negative, while always positive in the treated ones. To reduce a selection bias, we also used a multivariable analysis. On the HFMSE scale, age, gender, baseline value, and functional status contributed significantly to the changes, while the number of SMN2 copies did not contribute. The effect of these variables was less obvious on the RULM and 6MWT. Interpretation: Our results expand the available data on the effect of Nusinersen on type III patients, so far mostly limited to data from adult type III patients. [ABSTRACT FROM AUTHOR]

Aim Method Results Interpretation To investigate the timing of type 1 myotonic dystrophy (DM1) diagnosis in parents of affected children and describe children's perinatal characteristics and developmental outcomes.This was a descriptive case series of children with congenital myotonic dystrophy (CDM) and childhood‐onset myotonic dystrophy (ChDM). Parental timing of DM1 diagnosis and the perinatal, motor, and cognitive outcomes of paediatric patients were recorded.A total of 139 children followed by 12 highly specialized tertiary care neuromuscular centres in Italy and one tertiary neuromuscular centre in the USA were included: 105 children with CDM and 34 children with ChDM (mean age 8 years 8 months and 12 years 2 months respectively; 49 males and 17 males respectively). Seventy (50%) parents were diagnosed with adult‐onset DM1 after the affected child was diagnosed. Only 12 (17%) of the 69 parents known to be affected had prenatal testing.Of the 105 children with CDM, 98% had maternally inherited CDM, 36% were born preterm, 83% required a stay in the neonatal intensive care unit for more than 48 hours, 84% and 79% had ambulation and speech delay, and 84% had an IQ lower than 70. Of the 34 children with ChDM, 59% had paternally inherited ChDM, 91% were born at term, and 36% had an IQ lower than 70.Delay in diagnosing DM1 affects family planning. The prenatal and perinatal outcomes of the affected offspring emphasize the need for proactive counselling as parents may be reluctant to conduct prenatal testing. [ABSTRACT FROM AUTHOR]

Objective: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status. Methods: HFMSE longitudinal changes were assessed using piecewise linear mixed‐effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12‐month assessments. Results: A break point at age 7 years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and SMN2 copy number were not. The increase in response before the break point of age 7 years is significant only for SMA IIIA (β = 1.79, p < 0.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (β = −1.15, p < 0.0001) and IIIB (β = −0.69, p = 0.002). Interpretation: Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real‐world data of patients treated with commercially available drugs. ANN NEUROL 2020;88:1109–1117 [ABSTRACT FROM AUTHOR]

Aim: To report the differences between Performance of Upper Limb (PUL) versions 1.2 and 2.0, compare the measurement ability of the two versions, and compare their longitudinal performance in Duchenne muscular dystrophy.Method: Rasch analysis was performed on the dual data from three centres to confirm whether the two scales measure the same construct. Change scores in natural history for the different domains were compared for the two versions.Results: Rasch analysis demonstrated that both versions measure the same construct and that the PUL 2.0 was a better fit to the construct of motor performance and better able to detect change at 12 months in all levels of ability than the PUL 1.2. This was also true when change scores were reviewed over 2 years.Interpretation: Our results confirm that the PUL 1.2 and 2.0 versions detect change in all domains over 2 years. They also demonstrate that simplifying the original scoring of the PUL 1.2 for the revised PUL 2.0 maintains the validity of the construct and enhances the scale measurement qualities.What This Paper Adds: The original and revised Performance of Upper Limb (PUL) scales measure the same construct. Both scales detected change in all domains over 2 years. The PUL 2.0 enhances the measurement qualities of the scale. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to report 12-month changes after treatment with nusinersen in a cohort of 85 type I spinal muscular atrophy patients of ages ranging from 2 months to 15 years and 11 months.Methods: All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination-Section 2 (HINE-2).Results: Two of the 85 patients had 1 SMN2 copy, 61 had 2 copies, and 18 had 3 copies. In 4 patients the SMN2 copy number was not available. At baseline, the mean CHOP INTEND scores ranged between 0 and 52 (mean = 15.66, standard deviation [SD] = ±13.48), and the mean HINE-2 score was between 0 and 5 (mean = 0.69, SD = ±1.23). There was a difference between baseline and the 12-month scores on both the CHOP INTEND and the HINE-2 for the whole group (p < 0.001), the subgroups with 2 SMN2 copies (p < 0.001), and those with 3 SMN2 copies (p < 0.001). The difference was found not only in patients younger than 210 days at baseline (p < 0.001) but also in those younger than 5 years on the CHOP INTEND and younger than 2 years on the HINE-2.Interpretation: Our results, expanding the age range and the severity of type I patients treated with nusinersen over 1 year, provide additional data on the range of efficacy of the drug that will be helpful in making an informed decision on whether to start treatment in patients of different ages and severity. ANN NEUROL 2019;86:443-451. [ABSTRACT FROM AUTHOR]

Introduction: There is a growing need for a robust clinical measure to assess upper limb motor function in spinal muscular atrophy (SMA), as the available scales lack sensitivity at the extremes of the clinical spectrum. We report the development of the Revised Upper Limb Module (RULM), an assessment specifically designed for upper limb function in SMA patients.Methods: An international panel with specific neuromuscular expertise performed a thorough review of scales currently available to assess upper limb function in SMA. This review facilitated a revision of the existing upper limb function scales to make a more robust clinical scale.Results: Multiple revisions of the scale included statistical analysis and captured clinically relevant changes to fulfill requirements by regulators and advocacy groups.Conclusions: The resulting RULM scale shows good reliability and validity, making it a suitable tool to assess upper extremity function in the SMA population for multi-center clinical research. Muscle Nerve 55: 869-874, 2017. [ABSTRACT FROM AUTHOR]

Aim: Duchenne muscular dystrophy (DMD) is associated with neuropsychiatric disorders. The aim of the study was to characterize the DMD neuropsychiatric profile fully and to explore underlying genotype/phenotype associations.Method: One hundred and thirty males with DMD (mean age 9y 10mo, range 5-17y) in four European centres were included and completed IQ assessment and a neurodevelopmental-screening questionnaire. Of these, 87 underwent comprehensive neuropsychiatric assessment using structured diagnostic interview and parent-reported questionnaires.Results: The overall mean score on the neurodevelopmental questionnaire was significantly abnormal compared with the general population of children (p<0.001). On average, intelligence was below the population mean, with intellectual disability observed in 34 males (26%). Autistic spectrum disorder was identified in 18 (21%), hyperactivity in 21 (24%), and inattention in 38 (44%). Clinical levels of internalizing and externalizing problems were observed in 21 (24%) and 13 (15%) respectively. Over a third of males scored more than two measures of emotional, behavioural, or neurodevelopmental problems. Males with mutations at the 3' end of the DMD gene affecting all protein isoforms had higher rates of intellectual disability and clusters of symptoms.Interpretation: Males with DMD are at very high risk of neuropsychiatric disturbance, and this risk appears to increase with mutations at the 3' end of the gene. Patterns of symptom clusters suggest a DMD neuropsychiatric syndrome, which may require prompt evaluation and early intervention. [ABSTRACT FROM AUTHOR]

Introduction: With clinical trials underway, our objective was to construct a composite score of global function that could discriminate among people with spinal muscular atrophy (SMA).Methods: Data were collected from 126 participants with SMA types 2 and 3. Scores from the Hammersmith Functional Motor Scale-Expanded and Upper Limb Module were expressed as a percentage of the maximum score and 6-minute walk test as percent of predicted normal distance. A principal component analysis was performed on the correlation matrix for the 3 percentage scores.Results: The first principal component yielded a composite score with approximately equal weighting of the 3 components and accounted for 82% of the total variability. The SMA functional composite score, an unweighted average of the 3 individual percentage scores, correlated almost perfectly with the first principal component.Conclusions: This combination of measures broadens the spectrum of ability that can be quantified in type 2 and 3 SMA patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: This study explores burden and social and professional support in families of young patients with muscular dystrophies (MDs) in Italy. Methods: The study was carried out on 502 key relatives of 4- to 25-year-old patients suffering from Duchenne, Becker, or Limb-Girdle MD who were living with at least 1 adult relative. Results: A total of 77.1% of relatives reported feelings of loss, 74.0% had feelings of sadness, and 59.1% had constraints in leisure activities. Burden was higher among relatives of patients with higher disability and who spent more daily hours in caregiving. Practical difficulties were higher among relatives who perceived lower help in patient emergencies and less practical support by their social network. Psychological burden was higher in those relatives who were unemployed, those with poorer support in emergencies, and those with lower social contacts. Conclusions: Caring for patients with MDs may be demanding for relatives even in the early stages of these disorders, especially when social support is poor and the patient's disability increases. Muscle Nerve 52: 13-21, 2015 [ABSTRACT FROM AUTHOR]

The recent development of therapeutic approaches for Duchenne muscular dystrophy (DMD) has highlighted the need to identify clinical outcome measures for planned efficacy studies. Although several studies have reported the value of functional scales, timed tests, and measures of endurance aimed at ambulant individuals, less has been done to identify reliable measures of function in individuals who have lost ambulation. The aim of this paper is to provide a critical review of the existing literature on functional measures assessing upper extremity function in DMD. Four observer-rated, performance-based measures and four self-reported scales have been previously used in DMD. Each scale provides useful information but none reflects all the different levels of functional ability in activities of daily living observed in individuals with DMD at different ages. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to evaluate whether the visual analysis of muscle magnetic resonance imaging scans can identify specific patterns of muscle involvement. Methods We assessed scans from 83 patients with muscle disorders characterized by rigidity of the spine secondary to mutations in 4 different genes. The conditions studied were rigid spine syndrome ( SEPN1 defects), Bethlem myopathy, and Ullrich congenital muscular dystrophy, allelic disorders caused by Col6A1, Col6A2, and Col6A3 mutations, the autosomal dominant form of Emery-Dreifuss muscular dystrophy ( LMNA defects) and calpain-deficient limb girdle muscular dystrophy ( CAPN3 defects). The scans of 25 patients affected by other myopathies were also reviewed as a control group. The scans were compared with the previously described patterns. Results In 82% of the scans in the study group (68/83) the patterns were classified as 'typical' of 1 of the 5 forms studied, and in 7 (8%) were consistent with 1 of the reported patterns but not entirely typical. With one exception, the patterns identified were always consistent with the appropriate genetic diagnosis. The remaining scans (9%) had only minimal changes and were uninformative. None of the scans of the 25 patients in the control group had patterns that could be classified as typical of the 5 forms examined. The sensitivity to detect selective patterns in relation to the genetic diagnosis was 0.9. Interpretation These findings suggest that muscle magnetic resonance imaging could be used in clinical practice as an additional tool in the differential diagnosis of muscle disorders with prominent spinal rigidity. ANN NEUROL 2010;67:201-208 [ABSTRACT FROM AUTHOR]

Several clinical trials assessing children with hereditary neuromuscular disorders have been performed over the last decade. These studies highlighted issues related to design and performance of clinical studies assessing children with this group of disorders. This article reviews recent literature and clinical experience in this area, highlighting methodological shortcomings and disease-specific clinical confounding factors that should be considered for future study design. The state of the art of outcome measures in neuromuscular disorders will be discussed, and suggestions for future clinical trials are presented. [ABSTRACT FROM AUTHOR]

Interest in muscle MRI has been largely stimulated in the last few years by the recognition of an increasing number of genetic defects in the field of inherited neuromuscular disorders. Muscle ultrasound (US) and computed tomography (CT) have been used to detect the presence of muscle involvement in patients affected by these disorders, but until recently the use of muscle MRI has been, with a few exceptions, limited to detecting inflammatory forms. The aim of this review is to illustrate how muscle MRI, in combination with clinical evaluation, can contribute to the selection of appropriate genetic tests and more generally in the differential diagnosis of genetically distinct forms of neuromuscular disorders. Possible future applications of muscle MRI are also discussed. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose:Mechanisms inducing continuous spike–wave during slow sleep (CSWS) in encephalopathy with electrical status epilepticus during sleep are still unclear. Recently, some sporadic cases with early thalamic injury associated with CSWS have been reported. The aim of the study was to investigate in a population of patients with an early thalamic injury the presence of an activation of paroxysmal activities during sleep, their characteristics, and possible relations to neuroimaging and neuropsychological features.Methods:Thirty-two patients with prenatal or perinatal thalamic injuries, mostly due to a vascular mechanisms, were fully examined, including neuroimaging, EEG monitoring, and cognitive follow-up.Results and Conclusions:Twenty-nine of 32 patients showed major sleep EEG activation. Among these 29 patients, two different groups were distinguished: the first included the more or less typical CSWS (12 cases), generally with symmetry of spike and waves (SWs) and often with no spindle at all. The other cases had an usual asymmetry of SWs and presence or reduction of spindles, plus other atypical features concerning synchronism and morphology of SWs. Behavioral disorders were significantly more present in patients with a true CSWS; their improvement (and in one case of the three thoroughly followed the improvement of cognitive competence) paralleled the disappearance of CSWS. The generally predominant injury of the lateral aspect of the thalamus included reticular nucleus and ventral nuclei. An imbalance ofγ-aminobutyric acid (GABA)B- versus GABAA -mediated receptors may be evoked as a cofactor predisposing to CSWS. [ABSTRACT FROM AUTHOR]

Summary: Background: Wolf–Hirschhorn syndrome (WHS) is a well-known clinical entity caused by partial deletion of the short arm of one chromosome 4 (4p– syndrome). Seizures occur in almost all the cases, but studies on the electroclinical disorder and its evolution are still scarce. We present a longitudinal study of the electroclinical features in 10 children with WHS. Methods: Ten patients (five boys and five girls) underwent a detailed clinical assessment and a prolonged EEG study. Six of the 10 also had video-polygraphy. Results: Nine of the 10 patients had seizures; they were generalized or unilateral clonic and tonic–clonic, and atypical absences associated with myoclonic jerks. Age at onset of seizures varied from 1 day to 2.5 years. In all the patients, including the only one without seizures, two stereotyped EEG patterns were observed, consisting of (a) bursts of rhythmic (3–5 Hz), high-voltage slow waves located in the posterior regions and increased by sleep, or bursts of rapid spike–wave complexes in the centroparietal and parietooccipital regions; and (b) repetitive rapid posterior spikes. Sleep organization was constantly absent or very poor. The evolution of epilepsy was frequently good, with four seizure-free cases at the end of follow-up, two of them weaned from antiepileptic drugs (AEDs). Conclusions: Seizure onset in WHS also can occur at neonatal age. At least two electrical stereotyped patterns of the epileptic disorder are associated with a relevant disorganization of the sleep states. Prognosis of epilepsy is generally good both for the seizure control and for its evolution. [ABSTRACT FROM AUTHOR]

Reply to: The need for evidence-based treatment decisions in spinal muscular atrophy type 0 Thank you for giving the possibility to comment to the letter sent by Erbas and Gusset1 in reply to our case report describing treatment of a patient affected by the most severe form of spinal muscular atrophy with prenatal onset (type 0).2 We were pleased to see that the patient/family perspective on this topic is very much in line with the conclusions of our case report. This would help to better characterize both the severity of the cases before treatment and the full extent of the possible response to treatments in patients who may have different presentation and severity. [Extracted from the article]

ABSTRACT Introduction: A recent Rasch analysis performed on the Hammersmith Functional Motor Scale-Expanded (HFMSE) in patients with spinal muscular atrophy (SMA) identified issues impacting scale validity, redundant items, and disordered thresholds on some items. Methods: We modified the HMFSE scoring based on the Rasch analysis and on expert consensus to establish whether the traditional scoring overestimated the number of patients with changes within 2 points from baseline. Data were collected retrospectively from multicenter data sets in 255 type 2 and 3 SMA patients. Results: The mean 12-month changes using the new and the traditional scoring system did not differ significantly ( P > 0.05). The numbers of patients who improved or decreased by >2 points were also similar. Conclusions: The presence of outliers using the traditional scoring system was not due to overestimation of changes in activities that were tested bilaterally or to discrepancies in the scoring hierarchy of individual items. Muscle Nerve 52:435-437, 2015 [ABSTRACT FROM AUTHOR]

Introduction/Purpose Methods Results Discussion Conclusion Nusinersen, the first treatment approved for all spinal muscular atrophy (SMA) types, is administered intrathecally through lumbar puncture. We used ultrasound assistance or a landmark‐based technique to access the lumbar intrathecal space in adult SMA patients. This study aimed to evaluate the technical success and adverse events (AEs) in such patients using either technique over a long observation period.Fifty‐one adult patients received 507 consecutive interlaminar nusinersen administrations. Patients presented with both ‘uncomplicated spines’ or ‘complicated spines’; two patients had previous back surgery. Technical success and AEs were recorded using either technique. A generalised linear mixed model was applied to evaluate predictors of technical success and complications.An overall success rate of 99.6%, with only two procedures failing to reach the intrathecal space, and an overall optimal procedure rate of 90.3% have been reported. A total of 455 procedures (89.7%) were uneventfully performed. One (0.2%) case of severe AE (puncture of a bulky abdominal annexal cyst) was recorded. Twenty‐seven episodes (5.3%) of post‐dural puncture headache (PDPH) and 24 episodes (4.7%) of radicular or back pain, both successfully treated with medical therapy, have also been reported. Technical success was significantly associated with ‘complicated spines’ (P = 0.022) and the use of ultrasound assistance (P = 0.01), and the use of ultrasound was the only independent predictor of uncomplicated procedures (P = 0.007).In adult patients with SMA both landmark‐based and ultrasound‐assisted techniques are safe and effective even in the long term. The use of assistance is associated with technical success and can predict uncomplicated procedures.Our results support the use of ultrasonography in order to improve the success and reduce the burden of nusinersen intrathecal administration. [ABSTRACT FROM AUTHOR]