Sonia Messina | Università Di Messina (original) (raw)

Papers by Sonia Messina

Neurological Sciences, Apr 19, 2021

Spinal muscular atrophy (SMA) is a severe disorder of motor neurons and the most frequent cause o... more Spinal muscular atrophy (SMA) is a severe disorder of motor neurons and the most frequent cause of genetic mortality, due to respiratory complications. We are facing an exciting era with three available therapeutic options in a disease considered incurable for more than a century. However, the availability of effective approaches has raised up ethical, medical, and financial issues that are routinely faced by the SMA community. Each therapeutic strategy has its weaknesses and strengths and clinicians need to know them to optimize clinical care. In this review, the state of the art and the results and challenges of the new SMA therapeutic strategies are highlighted.

Questionnaire provided to the carers. Sample of the questionnaire submitted to the carers. (DOCX ... more Questionnaire provided to the carers. Sample of the questionnaire submitted to the carers. (DOCX 19 kb)

Neuromuscular Disorders, 2021

Patient report outcome measures in Spinal Muscular Atrophy (SMA) represent a potential complement... more Patient report outcome measures in Spinal Muscular Atrophy (SMA) represent a potential complement to observer rated scales which can be used to better understand treatment response. We developed, translated and validated an Italian version of the Spinal Muscular Atrophy Health Index (SMAHI), a disease-specific, patient reported outcome measure questionnaire, designed to estimate the patients' perception of disease burden. Test-retest reliability was assessed in 37 patients (16 children aged 12-17 and 21 adults) and was excellent in both cohorts. Internal consistency in an additional 98 patients (24 children, 74 adults) was also excellent (Cronbach's alpha = 0.93 and 0.91 respectively). In children the highest level of disease burden was generated from lower limb dysfunction and fatigue as well as their perception of decreased performance in social situations. Most patients in the adult cohort were sitters and complained of problems with upper limb functions as well as of fatigue. The SMAHI-IT was also able to differentiate between SMA types according to diseases severity. The results of our study demonstrate that the SMAHI can be considered a marker of disease-specific burden in patients with SMA with a high test-retest reliability and internal validity in Italian patients aged 12 and older.

Neurological Sciences, 2021

Clinical evaluation and laboratory data -Heat stroke (EHS) is a life-threatening illness characte... more Clinical evaluation and laboratory data -Heat stroke (EHS) is a life-threatening illness characterized by a core body temperature elevated over 40°C and central nervous system dysfunction resulting in delirium, convulsions, cerebellar involvement or coma. -Heat stroke results from exposure to a high environmental temperature (nonexertional heat stroke) or from strenuous exercise (exertional heat stroke). -Many similarities exist between Heat Stroke and Malignant Hyperthermia. (MH). It is a pharmacogenetic disorder caused by mutations in the skeletal muscle Ca2+ release channel (or ryanodine receptor, RyR1) characterized by episodes of uncontrolled muscle contracture triggered by halogenated anesthetics such as isoflurane or halothane. -MH and EHS share many common pathological features, including rhabdomyolysis, increases in serum creatine kinase, hyperkalemia, tachycardia, metabolic acidosis, and increased muscle production of inflammatory cytokines. -Two human RyR1 mutations (R401...

Neuromuscular Disorders, 2019

The aim of this prospective multicentric study was to document disease progression in young boys ... more The aim of this prospective multicentric study was to document disease progression in young boys affected by Duchenne muscular dystrophy (DMD) between age 3 and 6 years (±3 months) using the North Star Ambulatory Assessment scale. One hundred fifty-three DMD boys (573 assessments) younger than 6 years (mean: 4.68, SD: 0.84) with a genetically proven DMD diagnoses were included. Our results showed North Star Ambulatory Assessment scores progressively increased with age. The largest increase was observed between age 3 and 4 years but further increase was steadily observed until age of 6 years. Using a multiple linear regression analysis, we found that both the use of corticosteroids and the site of mutation significantly contributed to the North Star Ambulatory Assessment changes (p < 0.001). At each age point, boys on corticosteroid treatment had higher scores than corticosteroid naïve ones (p < 0.001). Similarly, patients with mutations downstream exon 44, had lower baseline scores and lower magnitude of changes compared to those with mutations located at the 5 end of the gene (p < 0,001). Very few boys achieved the age appropriate maximum score. These results provide useful information for the assessment and counselling of young DMD boys and for the design of clinical trials in this age group.

Neuromuscular Disorders, 2017

Journal of Neurology, 2017

of variance and Chi-square test, as appropriate, logistic regression models and Kaplan-Meier surv... more of variance and Chi-square test, as appropriate, logistic regression models and Kaplan-Meier survival analysis. Between-subgroup comparisons showed an older age at clinical observation (p = .006), at onset and at diagnosis (p = .002) in demented versus non demented ALS patients. After adjustment for these variables, diagnosis of dementia was significantly associated with higher odds of family history of ALS (p = .001) and frontotemporal dementia (p = .003) and of bulbar onset (p = .004), and lower odds of flail leg phenotype (p = .019) and spinal onset (p = .008). The median survival time was shorter in demented versus non-demented patients, especially in case of classical, bulbar and flail limb phenotypes and both bulbar and spinal onset. Our multicenter study emphasized the importance of an early diagnosis of comorbid dementia in ALS patients, which may have clinical impact and prognostic relevance.

Journal of Neuromuscular Diseases, 2016

Background: Myasthenia gravis (MG) is an autoimmune disorder presenting with fluctuating, fatigab... more Background: Myasthenia gravis (MG) is an autoimmune disorder presenting with fluctuating, fatigable muscle weakness. Initial symptoms classically involve ocular and proximal limb muscles. Rarely, MG may onset with unusual features, so it can be misdiagnosed with other neuromuscular diseases. Objective: To describe unusual and atypical presentations of MG in a large cohort of patients, considering and discussing diagnostic difficulties and pitfalls. Methods: We report on 21 out of 508 MG patients, coming to our department in the last 27 years and presenting with atypical or unusual features. The diagnosis was achieved performing a careful clinical examination, a proper neurophysiological assessment, the neostigmine test, the AChR and MuSK antibodies assay and chest CT-scan. Results: Patients with atypical/unusual MG onset were the 4.4% of all MG patients population. We describe seven different clinical categories: asymmetric distal upper limbs weakness, foot drop, isolated triceps brachii weakness and foot drop, post exertional axial weakness with dropped head, acute facial dyplegia, limb-girdle MG and MG with sudden lower limbs weakness and recurrent falls. Conclusions: Atypical and unusual presentations may increase the risk to misdiagnose or delay MG diagnosis. Isolated limb-girdle presentation is the most frequent atypical form in our series.

Journal of Molecular Neuroscience, 2016

Nemaline myopathy represents a group of clinically and genetically heterogeneous neuromuscular di... more Nemaline myopathy represents a group of clinically and genetically heterogeneous neuromuscular disorders. Different clinical-genetic entities have been characterized in the last few years, with implications for diagnostics and genetic counseling. Fifty percent of nemaline myopathy forms are due to NEB mutations, but genetic analysis of this large and complex gene by Sanger sequencing is time consuming and expensive. We selected 10 Italian patients with clinical and biopsy features suggestive for nemaline myopathy and negative for ACTA1, TPM2 and TPM3 mutations. We applied a targeted next-generation sequencing strategy designed to analyse NEB coding regions, the relative full introns and the promoter. We also evaluated copy number variations (by CGH array) and transcriptional changes by RNA Sanger sequencing, whenever possible. This combined strategy revealed 11 likely pathogenic variants in 8 of 10 patients. The molecular diagnosis was fully achieved in 3 of 8 patients, while only one heterozygous mutation was observed in 5 subjects. This approach revealed to be a fast and cost-effective way to analyse the large NEB gene in a small group of patients and might be promising for the detection of pathological variants of other genes featuring large coding regions and lacking mutational hotspots.

Current Drug Metabolism, 2016

Statins are inhibitors of hydroxy-methyl-glutaryl coenzymeA (HMG-CoA) reductase, the rate-limitin... more Statins are inhibitors of hydroxy-methyl-glutaryl coenzymeA (HMG-CoA) reductase, the rate-limiting enzyme involved in de novo cholesterol synthesis. The patient health profile need to be take in account during the interpretation of the variability in the outcome of drug therapy, as well as compliance with prescribed pharmacological treatments, and genetic profile. Several genetic polymorphisms that may play a role in the differences in response to lipid lowering therapy have recently been identified. Statins, today used to reduce Low Density Lipoprotein-Cholesterol (LDL-C), represent the treatment of choice in individuals with increased risk of Cardio-Vascular Disease (CVD), both in primary and secondary prevention of cardiovascular events. Regardless of the usefulness in a wide range of patients, the common interindividual genetic variability, but also phenotypic aspects, lead to resistance and adverse responses. A large number of candidate genes and many single nucleotide polymorphisms (SNPs) have been evaluated and related to pharmacokinetic and/or pharmacodynamic of statins. Despite these several findings there are still not enough evidence to recommend pharmacogenomic tests before starting statin therapy.

BioFactors (Oxford, England), Jan 31, 2015

Dystrophin lack in DMD causes neuronal nitric oxide synthase (nNOS) membrane delocalization which... more Dystrophin lack in DMD causes neuronal nitric oxide synthase (nNOS) membrane delocalization which in turn promotes functional muscle ischemia, and exacerbates muscle injury. Apoptosis and the exhaustion of muscle regenerative capacity are implicated in Duchenne muscular dystrophy (DMD) pathogenesis and therefore are relevant therapeutic targets. Genistein has been reported to have pro-proliferative effects, promoting G1/S cell phase transition through the induction of cyclin D1, and anti-apoptotic properties. We previously showed that genistein could reduce muscle necrosis and enhance regeneration with an augmented number of myogenin-positive satellite cells and myonuclei, ameliorating muscle function in mdx mice. In this study we evaluated the underlying mechanisms of genistein effect on muscle specimens of mdx and wild type mice treated for five weeks with genistein (2 mg/kg/i.p. daily) or vehicle. Western blot analysis show that genistein increased cyclin D1 and nNOS expression; ...

Journal of Neurology, 2015

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle di... more Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype-phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological

Neuromuscular Disorders, 2008

$Research paper thumbnail of Muscle fat-fraction and mapping in Duchenne muscular dystrophy: evaluation of disease distribution and correlation with clinical assessments$

Skeletal Radiology, 2011

To examine the usefulness of dual-echo dual-flip angle spoiled gradient recalled (SPGR) magnetic ... more To examine the usefulness of dual-echo dual-flip angle spoiled gradient recalled (SPGR) magnetic resonance imaging (MRI) technique in quantifying muscle fat fraction (MFF) of pelvic and thighs muscles as a marker of disease severity in boys with Duchenne muscular dystrophy (DMD), by correlating MFF calculation with clinical assessments. We also tried to identify characteristic patterns of disease distribution. Twenty consecutive boys (mean age, 8.6 years ± 2.3 [standard deviation, SD]; age range, 5-15 years; median age, 9 years;) with DMD were evaluated using a dual-echo dual-flip angle SPGR MRI technique, calculating muscle fat fraction (MFF) of eight muscles in the pelvic girdle and thigh (gluteus maximus, adductor magnus, rectus femoris, vastus lateralis, vastus medialis, biceps femoris, semitendinosus, and gracilis). Color-coded parametric maps of MFF were also obtained. A neurologist who was blinded to the MRI findings performed the clinical assessments (patient age, Medical Research Council score, timed Gower score, time to run 10 m). The relationships between mean MFF and clinical assessments were investigated using Spearman&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s rho coefficient. Positive and negative correlations were evaluated and considered significant if the P value was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05. The highest mean MFF was found in the gluteus maximus (mean, 46.3 % ± 24.5 SD), whereas the lowest was found in the gracilis muscle (mean, 2.7 % ± 4.7 SD). Mean MFF of the gluteus maximus was significantly higher than that of the other muscles (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), except for the adductor magnus and biceps muscles. A significant positive correlation was found between the mean MFF of all muscles and the patients age (20 patients; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.005), Medical Research Council score (19 patients; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), timed Gower score (17 patients; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.03), and time to run 10 m (20 patients; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). A positive correlation was also found between the mean MFF of the gluteus maximus muscle and the timed Gower score. Color-coded maps provided an efficient visual assessment of muscle fat content and its heterogeneous distribution. Muscle fat fraction calculation and mapping using the dual-echo dual-flip angle SPGR MRI technique are useful markers of disease severity and permit patterns of disease distribution to be identified in patients with DMD.

Mediterranean Journal of Clinical Psychology, 2015

Executive Functions are goal-directed neurocognitive processes that allow the management of cogni... more Executive Functions are goal-directed neurocognitive processes that allow the management of cognition and behavior. Executive Functions are essential to allow people to set goals, self-monitor, inhibit inappropriate responses, and generally engage in well-planned, flexible, future-oriented behavior. Metacognitive processes, in close alliance with executive functions, are viewed as integral components of awareness and emotional regulation. The influence of metacognition on planning, monitoring and mental flexibility has not been investigated. The aim of this pilot study was to examine the relationship between metacognition and executive functions in Amyotrophic Lateral Sclerosis patient's caregivers. Twenty-two caregivers were evaluated using the following instruments: Metacognition Questionnaire-30 and Wisconsin Card Sorting Test. Data analysis was performed using SPSS for Windows applying correlational analysis (Spearman’s Rho). We founded that total score of metacognition is p...

Acta Myologica, 2020

Objective The aim of this study was to use a structured questionnaire in a large cohort of Duchen... more Objective The aim of this study was to use a structured questionnaire in a large cohort of Duchenne Muscular Dystrophy (DMD) patients to assess caregivers and patients views on respiratory function and to establish if their responses were related to the patients’ age or level of functional impairment. Methods Questionnaires were administered to caregivers in 205 DMD patients of age between 3 and 36 years (115 ambulant, 90 non-ambulant), and to 64 DMD patients (3 ambulant, 61 non-ambulant) older than 18 years, subdivided into groups according to age, FVC, ambulatory and ventilatory status. Results Some differences were found in relation to FVC % values (p = 0.014), ambulatory (p = 0.043) and ventilatory status (p = 0.014). Nearly half of the caregivers expected deterioration over the next years, with the perspective of deterioration more often reported by caregivers of non-ambulant (p = 0.018) and ventilated patients (p = 0.004). Caregivers appeared to be aware of the relevance of re...

Brain, 2021

Strong evidence suggests that endoplasmic reticulum stress plays a critical role in the pathogene... more Strong evidence suggests that endoplasmic reticulum stress plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through altered regulation of proteostasis. Robust preclinical findings demonstrated that guanabenz selectively inhibits endoplasmic reticulum stress-induced eIF2α-phosphatase, allowing misfolded protein clearance, reduces neuronal death and prolongs survival in in vitro and in vivo models. However, its safety and efficacy in patients with ALS are unknown. To address these issues, we conducted a multicentre, randomized, double-blind trial with a futility design. Patients with ALS who had displayed an onset of symptoms within the previous 18 months were randomly assigned in a 1:1:1:1 ratio to receive 64 mg, 32 mg or 16 mg of guanabenz or placebo daily for 6 months as an add-on therapy to riluzole. The purpose of the placebo group blinding was to determine safety but not efficacy. The primary outcome was the proportion of patients progressing to h...