Exploring variability in cognitive functioning in patients with spinal muscular atrophy: a scoping review.

The cognitive functioning of individuals with spinal muscular atrophy (SMA) is not well understood, prompting a call for more research to better grasp cognitive involvement in SMA. This study aims to explore recent findings regarding cognitive outcomes in SMA patients, including correlations between clinical features and cognitive abilities. The investigation seeks to identify commonly used measures for assessing cognitive function in this patient population. A scoping review following the Joanna Briggs Institute methodology examined literature until December 2023. Two databases were searched along with relevant article references using specific terms such as "spinal muscular atrophy," "SMA," "cognitive," "abilities," "functions," "intellective," or "intellectual." Screening focused on titles and abstracts from English language peer-reviewed journals. After the initial research, 1452 articles were identified. Subsequent screening and selection led to the inclusion of 13 articles in the review. Among these studies, four indicated a cognitive trend within the normal range for SMA patients. In four other studies, the majority of patients fell within the normal range. However, smaller proportions were observed to be either above or below the norm compared to the controls. Three studies reported noted cognitive performance below the average, while two showed above-average scores. The scoping review suggests that most SMA patients have cognitive abilities similar to the general population, with types II and III showing even lesser impact. However, certain cognitive domains may be affected in type I patients, highlighting the need for further research to fully understand cognitive involvement in SMA.

Treatment with ataluren in four symptomatic Duchenne carriers. A pilot study.

Duchenne muscular dystrophy (DMD) is a devastating X-linked neuromuscular disorder caused by dystrophin gene deletions (75%), duplications (15-20%) and point mutations (5-10%), a small portion of which are nonsense mutations. Women carrying dystrophin gene mutations are commonly unaffected because the wild X allele may produce a sufficient amount of the dystrophin protein. However, approximately 8-10% of them may experience muscle symptoms and 50% of those over 40 years develop cardiomyopathy. The presence of symptoms defines the individual as an affected "symptomatic or manifesting carrier". Though there is no effective cure for DMD, therapies are available to slow the decline of muscle strength and delay the onset and progression of cardiac and respiratory impairment. These include ataluren for patients with nonsense mutations, and antisense oligonucleotides therapies, for patients with specific deletions. Symptomatic DMD female carriers are not included in these indications and little data documenting their management, often entrusted to the discretion of individual doctors, is present in the literature. In this article, we report the clinical and instrumental outcomes of four symptomatic DMD carriers, aged between 26 and 45 years, who were treated with ataluren for 21 to 73 months (average 47.3), and annually evaluated for muscle strength, respiratory and cardiological function. Two patients retain independent ambulation at ages 33 and 45, respectively. None of them developed respiratory involvement or cardiomyopathy. No clinical adverse effects or relevant abnormalities in routine laboratory values, were observed.

Social cognition in two brothers with Becker muscular dystrophy: an exploratory study revealing divergent behavioral phenotypes.

BACKGROUND AND OBJECTIVE: Only few studies investigated social cognition in Becker muscular dystrophy (BMD). However, brain dystrophin deficiency could be a neural substrate for cognitive, emotional, and neuropsychological features in BMD. METHODS: We compared interoceptive accuracy and interpersonal comfort distance in two brothers with BMD presenting with the same genetic deletion and a healthy control. When possible, we collected neuropsychological and psychopathological assessments. RESULTS: Our BMD patients were significantly different in interoceptive accuracy, with patient 1 being extremely accurate and patient 2 being significantly less accurate than his brother but more accurate than the control. Interestingly, they presented opposite patterns of interpersonal distance. Patient 1 was comfortable with very short interpersonal distance (≤50 cm from the confederate/object) vs the control and patient 2. By contrast, patient 2 preferred larger distance vs the control and patient 1. Patient 1 also presented difficulties in social and emotional skills on the psychopathological assessment. CONCLUSIONS: We are aware this is a small sample; nonetheless, this is also the first description of such aspects in BMD and the first report ever of such divergent behavioral pattern. As impaired social cognition affects the quality of life and social relationship, further studies are needed for a closer understanding of involved mechanisms.

A narrative review of the use of a cutting-edge virtual reality rehabilitation technology in neurological and neuropsychological rehabilitation.

BACKGROUND: Virtual reality (VR) interventions have been increasingly used in the rehabilitation of a wide range of neurological and neuropsychological dysfunctions. Findings of previous reviews showed positive and promising effects of VR-based interventions. However, they summarized findings on VR-based intervention carried out through different VR systems and tasks. OBJECTIVE: We carried out a narrative review with the aim of qualitatively synthesising the results of previous studies that used specific VR systems, i.e. the Khymeia -Virtual Reality Rehabilitation System, for treatment purposes. METHODS: We searched the literature in various databases (i.e. EMBASE, Web of Science, SCOPUS, PubMed and PubMed Central) for studies published until November 23, 2023. RESULTS: 30 studies were selected. The VRRS was used for neuromotor rehabilitation only in 13 studies, for cognitive rehabilitation in 11 studies, and for both neuromotor and cognitive rehabilitation in six studies. The study design was heterogeneous including 15 randomised controlled trials. CONCLUSION: After discussing each study according to the type of rehabilitation we concluded that the use and efficacy of VRRS rehabilitative intervention for increasing the neurological and neuropsychological functioning of patients are promising but more evidence is needed to make a comparison with conventional treatment. Future studies should also include long-term follow-up as well as cost-effectiveness analysis.

Factors associated with pharmacological treatment in children with attention-deficit/hyperactivity disorders: a retrospective study of a series of 77 cases in a single third-level reference Centre in Apulia region.

BACKGROUND: The present study analysed data on children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) who were referred to the ADHD reference centre of Scientific Institute IRCCS E. Medea (Brindisi, Italy) for ADHD pharmacotherapy initiation and monitoring overtime. The main aim of the study was to examine differences in pharmacological treatment status (i.e., treatment continuation vs discontinuation) between patients. METHODS: Seventy-seven children and adolescents (mean age at pharmacotherapy initiation = 9.5, standard deviation = 2.6) with ADHD received drugs treatment for ADHD at the reference center between January, 2013 and May, 2022. Demographic and clinical data were obtained from the Italian Registry for ADHD and medical records. Child Behavior Checklist (CBCL) available data were used. RESULTS: Pharmacological treatment status was examined for patients (n = 63) with at least 12 months of follow-up after the first pharmacological treatment for ADHD. After starting pharmacotherapy treatment, 77.8% (n = 49) patients were still on treatment whereas 22.2% (n = 14) discontinued it. No between group difference were observed in demographic and clinical data except for the intelligence quotient/intellectual disability and rule-breaking behavior (n = 40). CONCLUSIONS: This study stressed the need of periodical assessments, monitoring difficulties with treatment and/or reasons for poor treatment compliance to provide individualized care.

Pain assessment in autism: updating the ethical and methodological challenges through a state-of-the-art review.

Sensory features of autism include hypo- or hyper-reactivity to pain; however, previous studies on pain in autism lead to conflicting results. Here, we present the state of the art and the methodological challenges concerning pain perception in autism, focusing on studies that used standardized protocol as Quantitative Sensory Testing (QST) to measure perception. Despite there are still scant evidences found with the use of QST, they have challenged the presumed hyposensitivity to pain in autisms, which emerged from parents' reports. Both, peripheral and central mechanisms, have been found involved in typical features of perception in autism. Nonetheless, evidences with controlled protocols are still scarce, and even scarcer are studies focused on children. Overall, complex ethical challenges have to be overcome in order to collect subjective and objective measures from autistic children. With heterogeneous neurodevelopmental features, or intellectual disability, novel or modified protocols are needed.

Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias.

Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34). We compared age at onset, disease features, and progression by gene and variant. There were no features that reliably distinguished one of these SCAs from another, and several genes-CACNA1A, ITPR1, SPTBN2, and KCNC3-were associated with both adult-onset and infantile-onset forms of disease, which also differed in presentation. Nevertheless, progression was overall very slow, and STUB1-associated disease was the fastest. Several variants in CACNA1A showed particularly wide ranges in age at onset: one variant produced anything from infantile developmental delay to ataxia onset at 64 years of age within the same family. For CACNA1A, ITPR1, and SPTBN2, the type of variant and charge change on the protein greatly affected the phenotype, defying pathogenicity prediction algorithms. Even with next-generation sequencing, accurate diagnosis requires dialogue between the clinician and the geneticist.

Association between feeding/mealtime behavior problems and internalizing/externalizing problems in autism spectrum disorder, other neurodevelopmental disorders and typically developing children.

BACKGROUND: The aim of current study was to examine the nature and prevalence of feeding problems and mealtime behavior problems in children with autism spectrum disorder (ASD) comparing to children with other neurodevelopmental disorders (NNDs) and TD children. We also investigated the impact of intelligence quotient (IQ) and/or emotional and behavioral problems on feeding and mealtime behavior problems. METHODS: Participants completed the following tests: Social Communication Questionnaire (SCQ), Child Behavior Checklist (CBCL), Brief Autism Mealtime Behavior Inventory (BAMBI) and Behavioral Pediatric Feeding Assessment Scale (BPFAS). RESULTS: Children with ASD showed more feeding and mealtime behavior problems including food refusal (P<0.001, P<0.001) and limited variety of foods (P=0.014; P=0.018) compared with NDDs and TD children. ASD group showed more problems in mealtime behavior (P=0.034) and parent behaviors (P=0.028) compared to TD group. Internalizing (P=0.003) and externalizing (P=0.008) problems were positively related to parent frustration during mealtime in ASD group. CONCLUSIONS: These results suggest that routine screening for feeding and mealtime behavior problems among children with ASD is necessary to prevent dietary inadequacies that may be associated with eating habits.

Prevalence of Spinal Muscular Atrophy in the Era of Disease-Modifying Therapies: An Italian Nationwide Survey.

OBJECTIVE: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene. The aim of this study was to assess the prevalence of SMA and treatment prescription in Italy. METHODS: An online survey was distributed to 36 centers identified by the Italian government as referral centers for SMA. Data on the number of patients with SMA subdivided according to age, type, SMN2 copy number, and treatment were collected. RESULTS: One thousand two hundred fifty-five patients with SMA are currently followed in the Italian centers with an estimated prevalence of 2.12/100,000. Of the 1,255, 284 were type I, 470 type II, 467 type III, and 15 type IV with estimated prevalence of 0.48, 0.79, 0.79 and 0.02/100,000, respectively. Three patients with SMA 0 and 16 presymptomatic patients were also included. Approximately 85% were receiving one of the available treatments. The percentage of treated patients decreased with decreasing severity (SMA I: 95.77%, SMA II: 85.11%, SMA III: 79.01%). DISCUSSION: The results provide for the first time an estimate of the prevalence of SMA at the national level and the current distribution of patients treated with the available therapeutical options. These data provide a baseline to assess future changes in relation to the evolving therapeutical scenario.

Can symptomatic nmDuchenne carriers benefit from treatment with ataluren? Results of 193-month follow-up.

[This retracts the article DOI: 10.36185/2532-1900-058.].

Peripheral circulation disturbances in two consecutive children with spinal muscular atrophy and literature review.

Spinal muscular atrophy is a progressive and severe hereditary (autosomal recessive) neuromuscular disease characterized by lower motor neuron degeneration in the spinal cord and brainstem causing a clinical picture of progressive muscle atrophy and weakness of skeletal and respiratory muscles. There is an ongoing discussion on the extent to which other tissues might be affected in patients with SMA. Several animal models and some case reports or small case series report involvement of other organ systems, such as peripheral nerve, brain, muscle, heart, vascular system, and pancreas. Recent literature reviews identified a number of cases with vascular abnormalities. We present two consecutive cases of patients diagnosed with SMA who developed peripheral circulation disturbances and combine the findings with a thorough review the literature.

Emergencies cards for neuromuscular disorders 1st Consensus Meeting from UILDM - Italian Muscular Dystrophy Association Workshop report.

Acute hospitalisation may be required to support patients with Neuromuscular disorders (NMDs) mainly experiencing respiratory complications, swallowing difficulties, heart failure, urgent surgical procedures. As NMDs may need specific treatments, they should be ideally managed in specialized hospitals. Nevertheless, if urgent treatment is required, patients with NMD should be managed at the closest hospital site, which may not be a specialized centre where local emergency physicians have the adequate experience to manage these patients. Although NMDs are a group of conditions that can differ in terms of disease onset, progression, severity and involvement of other systems, many recommendations are transversal and apply to the most frequent NMDs. Emergency Cards (EC), which report the most common recommendations on respiratory and cardiac issues and provide indications for drugs/treatments to be used with caution, are actively used in some countries by patients with NMDs. In Italy, there is no consensus on the use of any EC, and a minority of patients adopt it regularly in case of emergency. In April 2022, 50 participants from different centres in Italy met in Milan, Italy, to agree on a minimum set of recommendations for urgent care management which can be extended to the vast majority of NMDs. The aim of the workshop was to agree on the most relevant information and recommendations regarding the main topics related to emergency care of patients with NMD in order to produce specific ECs for the 13 most frequent NMDs.

Neuromuscular disorders and transition from pediatric to adult care in a multidisciplinary perspective: a narrative review of the scientific evidence and current debate.

Objective: Standards of care and new genetic and molecular therapies have contributed to increasing life expectancy of patients with neuromuscular diseases (NMDs). This review presents the clinical evidence for an adequate transition from pediatric to adult care in patients with NMDs considering both physical and psychosocial aspects and attempts at identifying a general pattern of transition in the literature that can be used for all patients with NMDs. Method: A search was performed on PubMed, Embase and Scopus using generic terms that could be referred to the transition construct specifically related to NMDs. A narrative approach was used to summarise the available literature. Results: Our review shows that few or no studies explored the transition process from pediatric to adult care in neuromuscular diseases and tried to identify a general pattern of transition applicable to all NMDs. Conclusions: A transition process taking into consideration physical, psychological, social needs of patient and caregiver could produce positive outcomes. However, there is still no unanimous agreement in the literature on what it consists of and how to achieve an optimal and effective transition.

Exploring the Contribution of Proximal Family Risk Factors on SLC6A4 DNA Methylation in Children with a History of Maltreatment: A Preliminary Study.

The cumulative effects of proximal family risk factors have been associated with a high number of adverse outcomes in childhood maltreatment, and DNA methylation of the serotonin transporter gene (SLC6A4) has been associated with child maltreatment. However, the relationships between proximal family risk factors and SLC6A4 methylation remains unexplored. We examined the association among cumulative family risk factors, maltreatment experiences and DNA methylation in the SLC6A4 gene in a sample of 33 child victims of maltreatment. We computed a cumulative family risk (CFR) index that included proximal family risk factors, such as drug or alcohol abuse, psychopathology, parents' experiences of maltreatment/abuse in childhood, criminal history, and domestic violence. The majority of children (90.9%) experienced more than one type of maltreatment. Hierarchical regression models suggested that the higher the CFR index score and the number of maltreatment experiences, and the older the children, the higher the SLC6A4 DNA methylation levels. Although preliminary, our findings suggest that, along with childhood maltreatment experiences per se, cumulative proximal family risk factors are seemingly critically associated with DNA methylation at the SLC6A4 gene.

Peripheral nervous system manifestations of Shiga toxin-producing E. coli-induced haemolytic uremic syndrome in children.

BACKGROUND: The Neurological involvement is the most common extra-renal complication of Shiga toxin-producing E. coli-hemolytic uremic syndrome (HUS) or typical HUS. On brain magnetic resonance examination, main neurological signs encompass acute lesions of the basal ganglia and the white matter, which could usually regress after Eculizumab infusion. In contrast, peripheral nervous system (PNS) manifestations in typical HUS are very rare and, when occurring, they require a careful management of neurological sequelae and an intensive multidisciplinary neuro-rehabilitation program. CASE PRESENTATION: Here, we present two pediatric cases of severe and complicated typical HUS with PNS manifestations who required therapeutic treatment and an intensive multidisciplinary neuro-rehabilitation program. In both cases, PNS manifestations were followed by the recovery from typical HUS-related severe central neurological damage and manifested mainly with marked bilateral motor deficit and hyporeflexia/areflexia in the lower limbs. The peripheral polyneuropathy was treated with immunosuppressive therapy (methylprednisolone boluses, i.v. immunoglobulins, plasma exchange), followed by a prolonged intensive neuro-rehabilitation program. After 8 months of rehabilitation, both patients gained complete functional recovery. CONCLUSIONS: PNS manifestations during typical HUS are a rare event and potentially leading to severe disability. A timely clinical assessment is mandatory to set up a prompt therapeutic and rehabilitation program and to obtain a complete clinical and functional recovery.