Research Interests: Natural History, Medicine, Humans, Mutation, Female, and 13 moreDisease, Male, Proteins, Gene Duplication, Myelin Proteins, Cost of Illness, Cell Cycle Proteins, Cross Sectional Studies, Charcot Marie Tooth Disease, Mitochondrial Proteins, Connexins, Psychology and Cognitive Sciences, and Medical and Health Sciences
Background and purposeData are reported from the Italian CMT Registry.MethodsThe Italian CMT Registry is a dual registry where the patient registers and chooses a reference center where the attending clinician collects a minimal dataset... more
Background and purposeData are reported from the Italian CMT Registry.MethodsThe Italian CMT Registry is a dual registry where the patient registers and chooses a reference center where the attending clinician collects a minimal dataset of information and administers the Charcot–Marie–Tooth (CMT) Examination/Neuropathy Score. Entered data are encrypted.ResultsOverall, 1012 patients had registered (535 females) and 711 had received a genetic diagnosis. Demyelinating CMT (65.3%) was more common than axonal CMT2 (24.6%) and intermediate CMT (9.0%). The PMP22 duplication was the most frequent mutation (45.2%), followed by variants in GJB1 and MPZ (both ~10%) and MFN2 (3.3%) genes. A relatively high mutation rate in some “rare” genes (HSPB1 1.6%, NEFL 1.5%, SH3TC2 1.5%) and the presence of multiple mutation clusters across Italy was observed. CMT4A was the most disabling type, followed by CMT4C and CMT1E. Disease progression rate differed depending on the CMT subtype. Foot deformities and walking difficulties were the main features. Shoe inserts and orthotic aids were used by almost one‐half of all patients. Scoliosis was present in 20% of patients, especially in CMT4C. Recessive forms had more frequently walking delay, walking support need and wheelchair use. Hip dysplasia occurred in early‐onset CMT.ConclusionsThe Italian CMT Registry has proven to be a powerful data source to collect information about epidemiology and genetic distribution, clinical features and disease progression of CMT in Italy and is a useful tool for recruiting patients in forthcoming clinical trials.
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We report on a girl with a de novo inverted duplication of chromosome 8 (q21.2-q22.3) associated with a mild phenotype. We were able to establish the maternal origin of the rearranged chromosome. We discuss the correlation between... more
We report on a girl with a de novo inverted duplication of chromosome 8 (q21.2-q22.3) associated with a mild phenotype. We were able to establish the maternal origin of the rearranged chromosome. We discuss the correlation between genotype and phenotype on the basis of a review of the findings from individuals with partial dup(8q).
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The Charcot‐Marie‐Tooth disease Pediatric Scale (CMTPedS) is a Rasch‐built clinical outcome measure of disease severity. It is valid, reliable, and responsive to change for children and adolescents aged 3 to 20 years. The aim of this... more
The Charcot‐Marie‐Tooth disease Pediatric Scale (CMTPedS) is a Rasch‐built clinical outcome measure of disease severity. It is valid, reliable, and responsive to change for children and adolescents aged 3 to 20 years. The aim of this study was to translate and validate an Italian version of the CMTPedS using a validated framework of transcultural adaptation. The CMTPedS (Italian) was translated and culturally adapted from source into Italian by two experts in CMT with good English language proficiency. The two translations were reviewed by a panel of experts in CMT. The agreed provisional version was back translated into English by a professional translator. The definitive Italian version was developed during a consensus teleconference by the same panel. CMT patients were assessed with the final version of the outcome measure and a subset had a second assessment after 2 weeks to evaluate test‐retest reliability. Seventeen patients with CMT aged 5 to 20 years (eight female) were evaluated with the CMTPedS (Italian), and test‐retest was performed in three patients. The CMTPedS (Italian) showed a high test‐retest reliability. No patient had difficulty in completing the scale. The instructions for the different items were clearly understood by clinicians and therefore the administration of the outcome measure was straight forward and easily understood by the children assessed. The CMTPedS (Italian) will be used for clinical follow‐up and in clinical research studies in the Italian population. The data is fully comparable to that obtained from the English language version.
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We aimed to estimate the frequency of sleep disorders in children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC) and to evaluate the relations between sleep disorders and motor, cognitive, and behavioral... more
We aimed to estimate the frequency of sleep disorders in children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC) and to evaluate the relations between sleep disorders and motor, cognitive, and behavioral problems. One hundred and sixty-five children with CP ages 6-16 years (mean age, 11years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Intelligence Scale for Children and the Child Behavior Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. An abnormal total sleep score was found in 19% of children with CP; more than 40% of children had an abnormal score on at least one SDSC factor. The SDSC total score was significantly associated (P<.01) with mental retardation, epilepsy, CBCL scores, and level 5 on the GMFCS. Our results confirm that sleep disorders are common in children with cerebral palsy. The relationship between motor and cognitive behavior and epilepsy should be further explored to better understand how these factors influence one another to identify effective treatments and to improve the well-being of the child.
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Background: In hemiplegic children, the recognition of the activity limitation pattern and the possibility of grading its severity are relevant for clinicians while planning interventions, monitoring results, predicting outcomes.... more
Background: In hemiplegic children, the recognition of the activity limitation pattern and the possibility of grading its severity are relevant for clinicians while planning interventions, monitoring results, predicting outcomes. Objective: Aim of the study is to examine the reliability and validity of Besta Scale, an instrument used to measure in hemiplegic children from 18 months to 12 years of age both grasp on request (capacity) and spontaneous use of upper limb (performance) in bimanual play activities and in ADL. Design: Psychometric analysis of reliability and of validity of the Besta scale was performed. Setting: Outpatient study sample Methods: Reliability study: A sample of 39 patients was enrolled. The administration of Besta scale was video-recorded in a standardized manner. All videos were scored by 20 independent raters on subsequent viewing. 3 raters randomly selected from the 20-raters group rescored the same video two years later for intra-rater reliability. Intra and inter-rater reliability were calculated using Intraclass Correlation Coefficient (ICC) and Kendall's coefficient (K), respectively. Internal consistency reliability was assessed using Alpha's Chronbach coefficient. Validity study: a sample of 105 children was assessed 5 times (at t0 and 2, 3, 6 and 12 months later) by 20 independent raters. Each patient underwent at the same time to QUEST and Besta scale administration and assessment. Criterion validity was calculated using rho-Pearson coefficient. Results: Reliability study: The inter-rater reliability calculated with Kendall's coefficient resulted moderate K=0.47. The intra-rater (or test-retest) reliability for 3 raters was excellent (ICC=0.927). The Cronbach's alpha for internal consistency was 0.972. Validity study: Besta scale showed a good criterion validity compared to QUEST increasing by age and severity of impairment. Rho Pearson's correlation coefficient r was 0.81 (P<0.0001). Limitations. Besta scales in infants finds hard to distinguish between mild to moderately impaired hand function. Conclusions: Besta scale scoring system is a valid and reliable tool, utilizable in a clinical setting to monitor evolution of unimanual and bimanual manipulation and to distinguish hand's capacity from performance.
Research Interests: Cerebral Palsy, Medicine, Physical Therapy, Activities of Daily Living, Humans, and 15 moreChild, Female, Pubmed, Male, Hemiplegia, Infant, Observer Variation, Concurrent Validity, Hand, Reproducibility of Results, Task Performance and Analysis, Motor activity, Disability Evaluation, Child preschool, and Hand strength
Research Interests: Neurology, Pediatrics, Cerebral Palsy, Medicine, Physical Therapy, and 15 moreActivities of Daily Living, Prospective studies, Humans, Child, Female, Male, Hemiplegia, Grip strength, Psychomotor Performance, Disability Evaluation, Child preschool, Prospective Cohort Study, Medical and Health Sciences, functional outcome, and Hand strength
BackgroundEvidence regarding the management of several aspects of cerebral palsy improved in recent years. Still, discrepancies are reported in clinical practice. Italian professionals and stakeholders expressed the need of setting up... more
BackgroundEvidence regarding the management of several aspects of cerebral palsy improved in recent years. Still, discrepancies are reported in clinical practice. Italian professionals and stakeholders expressed the need of setting up updated, evidenced-based, shared statements, to address clinical practice in cerebral palsy rehabilitation. The objective of the present study was to provide an updated overview of the state of knowledge, regarding the management and motor rehabilitation of children and young people with cerebral palsy, as the framework to develop evidence-based recommendations on this topic.MethodsGuidelines and systematic reviews were searched, relative to evidence-based management and motor treatment, aimed at improving gross motor and manual function and activities, in subjects with cerebral palsy, aged 2–18 years. A systematic search according to the Patients Intervention Control Outcome framework was executed on multiple sites. Independent evaluators provided sel...
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BACKGROUND AND AIMS The pediatric Charcot-Marie-Tooth (CMT) specific Quality of Life (QOL) outcome measure (pCMT-QOL) is a recently developed and validated patient reported measure of health QOL for children with CMT. The aim of this... more
BACKGROUND AND AIMS The pediatric Charcot-Marie-Tooth (CMT) specific Quality of Life (QOL) outcome measure (pCMT-QOL) is a recently developed and validated patient reported measure of health QOL for children with CMT. The aim of this study was to provide and validate an Italian version of the pCMT-QOL. METHODS The original English version was translated and adapted into Italian using standard procedures. pCMT-QOL was administered to patients genetically diagnosed with CMT, aged 8 to 18 years. A retest was given 2 weeks later to assess reliability in all patients. RESULTS A total of 22 patients (median age 14 years, DS 2.5; M:F 1:1) affected with CMT (19 CMT1A, 2 CMT2A, 1 CMT2K) were assessed as part of their clinical visit. The Italian-pCMT-QOL demonstrate a high test-retest reliability. None of the patients experienced difficulty in completing the questionnaire, no further corrections were needed after administration in patients. INTERPRETATION The Italian-pCMT-QOL is a reliable, culturally adapted, and comparable version of the original English pCMT-QOL.
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BACKGROUND Spinal muscular atrophy type 1 is a motor neuron disorder resulting in death or the need for permanent ventilation by age 2 years. We aimed to evaluate the safety and efficacy of onasemnogene abeparvovec (previously known as... more
BACKGROUND Spinal muscular atrophy type 1 is a motor neuron disorder resulting in death or the need for permanent ventilation by age 2 years. We aimed to evaluate the safety and efficacy of onasemnogene abeparvovec (previously known as AVXS-101), a gene therapy delivering the survival motor neuron gene (SMN), in symptomatic patients (identified through clinical examination) with infantile-onset spinal muscular atrophy. METHODS STR1VE was an open-label, single-arm, single-dose, phase 3 trial done at 12 hospitals and universities in the USA. Eligible patients had to be younger than 6 months and have spinal muscular atrophy with biallelic SMN1 mutations (deletion or point mutations) and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes per kg) for 30-60 min. During the outpatient follow-up, patients were assessed once per week, beginning at day 7 post-infusion for 4 weeks and then once per month until the end of the study (age 18 months or early termination). Coprimary efficacy outcomes were independent sitting for 30 s or longer (Bayley-III item 26) at the 18 month of age study visit and survival (absence of death or permanent ventilation) at age 14 months. Safety was assessed through evaluation of adverse events, concomitant medication usage, physical examinations, vital sign assessments, cardiac assessments, and laboratory evaluation. Primary efficacy endpoints for the intention-to-treat population were compared with untreated infants aged 6 months or younger (n=23) with spinal muscular atrophy type 1 (biallelic deletion of SMN1 and two copies of SMN2) from the Pediatric Neuromuscular Clinical Research (PNCR) dataset. This trial is registered with ClinicalTrials.gov, NCT03306277 (completed). FINDINGS From Oct 24, 2017, to Nov 12, 2019, 22 patients with spinal muscular atrophy type 1 were eligible and received onasemnogene abeparvovec. 13 (59%, 97·5% CI 36-100) of 22 patients achieved functional independent sitting for 30 s or longer at the 18 month of age study visit (vs 0 of 23 patients in the untreated PNCR cohort; p<0·0001). 20 patients (91%, 79-100]) survived free from permanent ventilation at age 14 months (vs 6 [26%], 8-44; p<0·0001 in the untreated PNCR cohort). All patients who received onasemnogene abeparvovec had at least one adverse event (most common was pyrexia). The most frequently reported serious adverse events were bronchiolitis, pneumonia, respiratory distress, and respiratory syncytial virus bronchiolitis. Three serious adverse events were related or possibly related to the treatment (two patients had elevated hepatic aminotransferases, and one had hydrocephalus). INTERPRETATION Results from this multicentre trial build on findings from the phase 1 START study by showing safety and efficacy of commercial grade onasemnogene abeparvovec. Onasemnogene abeparvovec showed statistical superiority and clinically meaningful responses when compared with observations from the PNCR natural history cohort. The favourable benefit-risk profile shown in this study supports the use of onasemnogene abeparvovec for treatment of symptomatic patients with genetic or clinical characteristics predictive of infantile-onset spinal muscular atrophy type 1. FUNDING Novartis Gene Therapies.
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In hemiplegic children, the recognition of the activity limitation pattern and the possibility of grading its severity are relevant for clinicians while planning interventions, monitoring results, predicting outcomes. Aim of the study is... more
In hemiplegic children, the recognition of the activity limitation pattern and the possibility of grading its severity are relevant for clinicians while planning interventions, monitoring results, predicting outcomes. Aim of the study is to examine the reliability and validity of Besta Scale, an instrument used to measure in hemiplegic children from 18 months to 12 years of age both grasp on request (capacity) and spontaneous use of upper limb (performance) in bimanual play activities and in ADL. Psychometric analysis of reliability and of validity of the Besta scale was performed. Outpatient study sample Reliability study: A sample of 39 patients was enrolled. The administration of Besta scale was video-recorded in a standardized manner. All videos were scored by 20 independent raters on subsequent viewing. 3 raters randomly selected from the 20-raters group rescored the same video two years later for intra-rater reliability. Intra and inter-rater reliability were calculated using ...
Research Interests: Cerebral Palsy, Medicine, Physical Therapy, Activities of Daily Living, Humans, and 15 moreChild, Female, Pubmed, Male, Hemiplegia, Infant, Observer Variation, Concurrent Validity, Hand, Reproducibility of Results, Task Performance and Analysis, Motor activity, Disability Evaluation, Child preschool, and Hand strength
We report on a girl with a de novo inverted duplication of chromosome 8 (q21.2-q22.3) associated with a mild phenotype. We were able to establish the maternal origin of the rearranged chromosome. We discuss the correlation between... more
We report on a girl with a de novo inverted duplication of chromosome 8 (q21.2-q22.3) associated with a mild phenotype. We were able to establish the maternal origin of the rearranged chromosome. We discuss the correlation between genotype and phenotype on the basis of a review of the findings from individuals with partial dup(8q).
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Tetrabenazine has been studied with a variety of hyperkinetic movement disorders, but there is limited and empirical literature on the potential efficacy of tetrabenazine in children with dyskinetic cerebral palsy (DCP). The purpose of... more
Tetrabenazine has been studied with a variety of hyperkinetic movement disorders, but there is limited and empirical literature on the potential efficacy of tetrabenazine in children with dyskinetic cerebral palsy (DCP). The purpose of this study was to evaluate the efficacy of tetrabenazine in a sample of children with DCP using the Movement Disorders—Childhood Rating Scale 4–18 Revised (MD-CRS 4–18 R). The study is a multicenter retrospective longitudinal study in which the participants were selected from the databases of each Center involved, according to detailed inclusion criteria. The study was performed on 23 children and adolescents (19 male and 4 females; mean age 8.28 years, SD 3.59) with DCP having been evaluated before starting the treatment (baseline), after 6 and 12 months of treatment and in a sub-cohort after >2 years follow-up. A linear mixed model was used to evaluate the effects of the different timings on each MD-CRS 4–18 R Index (Index I, Index II, and Global...
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Changes of gait pattern in children with Charcot-Marie-Tooth disease type 1A: a 18 months follow-up study
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Research Interests: Rehabilitation, Treatment Outcome, Cerebral Palsy, Research, Medicine, and 15 morePhysical Medicine and Rehabilitation, Physical Therapy, Italy, Prospective studies, Humans, Child, Female, Male, Hemiplegia, American, Clinical Sciences, Study design, Physical Restraint, Logistic Models, and Child preschool
Research Interests: Rehabilitation, Cerebral Palsy, Exercise therapy, Medicine, Physical Medicine and Rehabilitation, and 15 morePhysical Therapy, Activities of Daily Living, Humans, Child, Female, Male, Hemiplegia, American, Clinical Sciences, Randomized Controlled Trial, Hand, Physical Restraint, Motor activity, Recovery of Function, and Child preschool
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Research Interests: Mechanical Engineering, Kinetics, Locomotion, Adolescent, Humans, and 15 moreChild, Gait Analysis, Female, Male, Measurement Error, Electromyography, Clinical Sciences, Aged, Gait and Posture, Adult, CHarcot Marie Tooth, Elsevier, Healthy Subjects, Charcot Marie Tooth Disease, and Biomechanical Phenomena
Abstracts / Gait & Posture 37 (2013) S1–S31 S11Fig. 1. Materialsandmethods:FunctionalMagneticResonanceImag-ing (fMRI) task, consisting in observation of spatial targettrajectories and their recall from memory, was administered to... more
Abstracts / Gait & Posture 37 (2013) S1–S31 S11Fig. 1. Materialsandmethods:FunctionalMagneticResonanceImag-ing (fMRI) task, consisting in observation of spatial targettrajectories and their recall from memory, was administered to 22healthysubjects.Theobservedmovementsconsistedinupperlimbreaching tasks (Fig. 1A) and computer generated dot movements(Fig. 1B) visualized in subsequent random sequences. The subjecthad to decide if trajectories were congruent with the given target.Control on responses was tested introducing trials with congruentand incongruent targets.Results: The observation of upper limb reaching and dot move-ments induced similar patterns of activations according to acaudo-rostral pathway (including specific areas of the occipital,temporal,parietal,andfrontallobes),seeorangeoverlappingareasin Fig. 2. Similarly, evidence of visual processing of movementswerefoundforthesubsequentretrievaloftheobservedmovement.Furthermore, activations of frontal cortical areas were evidentwhenthesubjectwasdecidingwhetherthetargettrajectorieswerecongruent or not.Discussion: We identified the neural pathways associatedwith visual processing of movement stimuli used in upper limbrobot-mediated training. In both study conditions, activationswere elicited in cerebral areas involved in visual perception, sen-sory integration, recognition of movement, re-mapping on thesomatosensory and motor cortex, memory recall and responsecontrol. Furthermore, we documented the brain’s ability to assim-ilate abstract object movements trajectories with human motorgestures. This results suggest the appropriateness of the visualfeedback provided during robotic motor training. The results ofour study highlight the role of fMRI in improving the understand-ing of visual motor analysis and decision processing during brainreorganisation after training.
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Mitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role in mitochondrial fusion. Mutations in MFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type... more
Mitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role in mitochondrial fusion. Mutations in MFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type 2A (CMT2A), the commonest axonal form of CMT, with significant allelic heterogeneity. Previous, moderately-sized, cross sectional genotype-phenotype studies of CMT2A have described the phenotypic spectrum of the disease, but longitudinal natural history studies are lacking. In this large multicentre prospective cohort study of 196 patients with dominant and autosomal recessive CMT2A, we present an in-depth genotype-phenotype study of the baseline characteristics of patients with CMT2A and longitudinal data (1–2 years) to describe the natural history. A childhood onset of autosomal dominant CMT2A is the most predictive marker of significant disease severity and is independent of the disease duration. When compared to adult onset autosomal dominant CMT...
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Pain is a common and disabling symptom in patients with stroke, multiple sclerosis (MS), cerebral palsy (CP), spinal cord injury (SCI) and other conditions associated with spasticity, but data on its prevalence, and natural history, as... more
Pain is a common and disabling symptom in patients with stroke, multiple sclerosis (MS), cerebral palsy (CP), spinal cord injury (SCI) and other conditions associated with spasticity, but data on its prevalence, and natural history, as well as guidelines on its assessment and treatment in the field of neurorehabilitation, are largely lacking. The Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) searched and evaluated current evidence on the frequency, evolution, predictors, assessment, and pharmacological and non-pharmacological treatment of pain in patients with stroke, MS, CP, SCI and other conditions associated with spasticity. Patients with stroke, MS, CP, and SCI may suffer from pain related to spasticity, as well as nociceptive and neuropathic pain (NP), whose prevalence, natural history, impact on functional outcome, and predictors are only partially known. Diagnosis and assessment of the different types of pain in these patients is important, because their...
Research Interests: Multiple sclerosis, Evidence Based Medicine, Cerebral Palsy, Medicine, Pain Management, and 11 moreItaly, Neurological Rehabilitation, Stroke, Humans, Spinal Cord Injuries, Pain Measurement, Translational Medical Research, Neuralgia, Muscle spasticity, Nociceptive pain, and Outcome assessment (Health care)
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Social distancing due to the COVID-19 pandemic represented a golden opportunity to implement telerehabilitation for clinical groups of children. The present study aims to show the impact that telerehabilitation had on the experience of... more
Social distancing due to the COVID-19 pandemic represented a golden opportunity to implement telerehabilitation for clinical groups of children. The present study aims to show the impact that telerehabilitation had on the experience of well-being of children with special needs being treated at the Foundation IRCCS Neurological Institute ‘C. Besta’ in Milan (Specific Learning Disorders and Cerebral Palsy diagnosis); it aims to do so by comparing it with experiences of those who did not undertake telerehabilitation despite the diagnosis during the pandemic, and with typically developing children. Results show that the three groups differed in the Support, Respect and Learning dimensions of well-being experience. Post hoc comparisons revealed that children with Specific Learning Disorders and Cerebral Palsy scored higher than normotypical children in Support and in Respect scales. Furthermore, children who experienced telerehabilitation showed the highest scores on the Learning scale i...
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Objective:This study examined the association between body mass index (BMI) and disability in children with Charcot-Marie-Tooth disease (CMT).Methods:We conducted a cross-sectional analysis of 477 patients with CMT aged 3-20 years from... more
Objective:This study examined the association between body mass index (BMI) and disability in children with Charcot-Marie-Tooth disease (CMT).Methods:We conducted a cross-sectional analysis of 477 patients with CMT aged 3-20 years from the Inherited Neuropathy Consortium, and 316 age-and-sex matched healthy children from the 1000 Norms Project. BMI was categorised according to the International Obesity Task Force (IOTF) criteria, and BMI categorisation was compared with healthy children. IOTF categories (adult equivalent BMI cut points) were: severely underweight (BMI<17kg/m2); underweight (BMI≥17 to <18.5kg/m2); healthy weight (BMI≥18.5 to <25kg/m2); overweight (BMI ≥25 to <30kg/m2); obese (BMI ≥30kg/m2). Scores on the 0-44 point CMT Pediatric Scale (CMTPedS), a well-validated measure of disability, were examined in relation to BMI.Results:There was a higher proportion of children with CMT categorised as severely underweight (5.7%vs0.3%), underweight (10.3%vs5.1%), and ...
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The CMT Pediatric Scale (CMTPedS) is a reliable, valid, and responsive clinical outcome measure of disability in children with CMT. The aim of this study was to identify the most responsive patient subset(s), based on the standardized... more
The CMT Pediatric Scale (CMTPedS) is a reliable, valid, and responsive clinical outcome measure of disability in children with CMT. The aim of this study was to identify the most responsive patient subset(s), based on the standardized response mean (SRM), to optimize the CMTPedS as a primary outcome measure for upcoming clinical trials. Analysis was based on a 2‐year natural history data from 187 children aged 3–20 years with a range of CMT genetic subtypes. Subsets based on age (3–8 years), disability level (CMTPedS score 0–14), and CMT type (CMT1A) increased the SRM of the CMTPedS considerably. Refining the inclusion criteria in clinical trials to younger, mildly affected cases of CMT1A optimizes the responsiveness of the CMTPedS.
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Cerebral palsy (CP) is still the most common cause of disability developing in infancy. How such a complex disorder affects adult life raises important questions on the critical issues to consider and the most appropriate care pathway... more
Cerebral palsy (CP) is still the most common cause of disability developing in infancy. How such a complex disorder affects adult life raises important questions on the critical issues to consider and the most appropriate care pathway right from early childhood. We conducted a multicenter study on a sample of 109 individuals with CP followed up from infancy and recalled for an assessment at ages ranging between 18 and 50 years (mean age 26 years). Semi-structured interviews and specific questionnaires (SF36, LIFE-H and Hollingshead Index) were conducted to assess general psychological state, quality of life, and socio-economic conditions. Our findings showed a globally positive perception of quality of life, albeit with lower scores for physical than for mental health. Our cases generally showed good scores on participation scales, though those with more severe forms scored lower on parameters such as mobility, autonomy, and self-care. These findings were investigated in more depth in interviews, in which our participants painted a picture showing that gradual improvements have been made in several aspects over the years, in the academic attainment and employment, for instance. On the downside, our sample reported persistent limitations on autonomy in daily life. As for the more profound psychological domain, there was evidence of suffering due to isolation and relational difficulties in most cases that had not emerged from the questionnaires. Our data have possible implications for the management of CP during childhood, suggesting the need to avoid an exclusive focus on motor function goals, and to promote strategies to facilitate communication, participation, autonomy, and social relations.
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Charcot‐Marie‐Tooth disease (CMT) is a clinically and genetically heterogeneous group of distal symmetric polyneuropathies due to progressive and length‐dependent degeneration of peripheral nerves. Cranial nerve involvement has been... more
Charcot‐Marie‐Tooth disease (CMT) is a clinically and genetically heterogeneous group of distal symmetric polyneuropathies due to progressive and length‐dependent degeneration of peripheral nerves. Cranial nerve involvement has been described in association with various CMT‐genes mutations, such as GDAP1, TRPV4, MFN2, MTMR2 and EGR2. Compound heterozygous mutations in the TRIM2 gene, encoding an E3 ubiquitin ligase, were previously identified in two patients with early‐onset axonal CMT (CMT2). One of them also had bilateral vocal cord paralysis. The aim of this study is to further delineate the phenotypic and molecular genetic features of TRIM2‐related CMT. We studied clinical, genetic and neurophysiological aspects of two unrelated CMT2 patients. Genetic analysis was performed by next generation sequencing of a multigene CMT panel. Patients presented with congenital hypotonia and bilateral clubfoot, delayed motor milestones, and severely progressive axonal neuropathy. Interestingly, along with vocal cord paralysis, they exhibited clinical features secondary to the involvement of several other cranial nerves, such as facial weakness, dysphagia, dyspnoea and acoustic impairment. Genetic analysis revealed two novel TRIM2 mutations in each patient. Our results expand the genotypic and phenotypic spectrum of TRIM2 deficiency showing that cranial nerves involvement is a core feature in this CMT2‐subtype. Its finding should prompt physicians to suspect TRIM2 neuropathy. Conversely, patients carrying TRIM2 variants should be carefully evaluated for the presence of cranial nerve dysfunction in order to prevent and manage its impact on auditory and respiratory function and nutrition.
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ObjectiveTo evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A... more
ObjectiveTo evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A (CMT1A).MethodsPatients with CMT1A from 18 sites of the Inherited Neuropathies Consortium were evaluated between 2009 and 2018. Weighted CMTNS and CMTES modified category responses were developed with Rasch analysis of the standard scores. Change from baseline for CMTNS-R and CMTES-R was estimated with longitudinal regression models.ResultsBaseline CMTNS-R and CMTES-R scores were available for 517 and 1,177 participants, respectively. Mean ± SD age of participants with available CMTES-R scores was 41 ± 18 (range 4–87) years, and 56% were female. Follow-up CMTES-R assessments at 1, 2, and 3 years were available for 377, 321, and 244 patients. A mixed regression model showed significant change in CMTES-R score at years 2 through 6 compared to baseline (mean change ...
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Introduction: Balance impairment contributes to gait dysfunction, falls, and reduced quality of life in adults with Charcot–Marie–Tooth disease (CMT) but has been minimally examined in pediatric CMT. Methods: The CMT Pediatric Scale... more
Introduction: Balance impairment contributes to gait dysfunction, falls, and reduced quality of life in adults with Charcot–Marie–Tooth disease (CMT) but has been minimally examined in pediatric CMT. Methods: The CMT Pediatric Scale (CMTPedS) was administered to 520 children with CMT. Associations between balance function (Bruininks–Oseretsky Test of Motor Proficiency [BOT‐2]) and sensorimotor and gait impairments were investigated. Results: Daily trips/falls were reported by 42.3% of participants. Balance (BOT‐2) varied by CMT subtype, was impaired in 42% of 4‐year‐olds, and declined with age (P < 0.001). Vibration (P < 0.001), pinprick (P < 0.004), ankle dorsiflexion strength (P < 0.001), and foot alignment (P < 0.004) were associated with BOT‐2 balance (adjusted R2 = 0.28). The visual dependence of balance increased with age. Discussion: Balance impairment occurs from a young age in children with CMT. Balance intervention studies are required in pediatric CMT and should consider the degree of sensorimotor impairment, foot malalignment, and visual dependence. Muscle Nerve, 2019