Publications by authors named "Angela Berardinelli"

76 Publications

Muscle Fiber Conduction Velocity Correlates With the Age at Onset in Mild FSHD Cases.

Front Physiol 2021 17;12:686176. Epub 2021 Jun 17.

Criams-Sport Medicine Centre Voghera, University of Pavia, Pavia, Italy.

A majority of patients with facioscapulohumeral muscular dystrophy (FSHD) report severe fatigue. The aim of this study was to explore whether fatigability during a performance task is related to the main clinical features of the disease in mildly affected patients. A total of 19 individuals with a molecular genetic-based diagnosis of FSHD (median D4Z4 deletion length of 27 kb) performed two isometric flexions of the dominant biceps brachii at 20% of their maximal voluntary contraction (MVC) for 2 min, and then at 60% MVC until exhaustion. Fatigability indices (average rectified value, mean frequency, conduction velocity, and fractal dimension) were extracted from the surface electromyogram (sEMG) signal, and their correlations with age, age at onset, disease duration, D4Z4 contraction length, perceived fatigability, and clinical disability score were analyzed. The conduction velocity during the low level contraction showed a significant negative correlation with the age at onset ( < 0.05). This finding suggest the assessment of conduction velocity at low isometric contraction intensities, as a potential useful tool to highlight differences in muscle involvement in FSHD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.686176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247588PMC
June 2021

North Star Ambulatory Assessment changes in ambulant Duchenne boys amenable to skip exons 44, 45, 51, and 53: A 3 year follow up.

PLoS One 2021 25;16(6):e0253882. Epub 2021 Jun 25.

Department of Neurosciences, Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children's Hospital, Rome, Italy.

Introduction: The aim of this study was to report 36-month longitudinal changes using the North Star Ambulatory Assessment (NSAA) in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53.

Materials And Methods: We included 101 patients, 34 had deletions amenable to skip exon 44, 25 exon 45, 19 exon 51, and 28 exon 53, not recruited in any ongoing clinical trials. Five patients were counted to skip exon 51 and 53 since they had a single deletion of exon 52.

Results: The difference between subgroups (skip 44, 45, 51 and 53) was significant at 12 (p = 0.043), 24 (p = 0.005) and 36 months (p≤0.001).

Discussion: Mutations amenable to skip exons 53 and 51 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had higher scores both at baseline and at follow up.

Conclusion: Our results confirm different progression of disease in subgroups of patients with deletions amenable to skip different exons. This information is relevant as current long term clinical trials are using the NSAA in these subgroups of mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253882PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232423PMC
June 2021

Have Duchenne Muscular Dystrophy Patients an Increased Cancer Risk?

J Neuromuscul Dis 2021 May 19. Epub 2021 May 19.

Nemo Sud Clinical Centre for Neuromuscular Disorders, Messina, Italy.

Background: Increasing evidence suggests that Duchenne muscular dystrophy (DMD) gene is involved in the occurrence of different types of cancer. Moreover, development of sarcomas was reported in mdx mice, the murine model of DMD, in older age. So far, nine isolated DMD patients were reported with concomitant cancer, four of whom with rhabdomyosarcoma (RMS), but no systematic investigation was performed about the true incidence of cancer in DMD.

Methods: All members of the Italian Association of Myology were asked about the occurrence of cancer in their DMD patients in the last 30 years.

Results: Four DMD patients with cancer were reported after checking 2455 medical records. One developed brain tumour at the age of 35 years. Two patients had alveolar RMS at 14 and 17 years of age. The fourth patient had a benign enchondroma when 11-year-old.

Conclusion: Prevalence of cancer in general in the Italian DMD patients does not seem to be different from that in the general population with the same age range. Although the small numbers herein presented do not allow definitive conclusion, the frequent occurrence of RMS in DMD patients raises an alert for basic researchers and clinicians. The role of DMD gene in cancer merits further investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JND-210676DOI Listing
May 2021

Pilot Study on Quantitative Cervical Cord and Muscular MRI in Spinal Muscular Atrophy: Promising Biomarkers of Disease Evolution and Treatment?

Front Neurol 2021 29;12:613834. Epub 2021 Mar 29.

Advanced Imaging and Radiomics Center, Neuroradiology Department, IRCCS Mondino Foundation, Pavia, Italy.

Nusinersen is a recent promising therapy approved for the treatment of spinal muscular atrophy (SMA), a rare disease characterized by the degeneration of alpha motor neurons (αMN) in the spinal cord (SC) leading to progressive muscle atrophy and dysfunction. Muscle and cervical SC quantitative magnetic resonance imaging (qMRI) has never been used to monitor drug treatment in SMA. The aim of this pilot study is to investigate whether qMRI can provide useful biomarkers for monitoring treatment efficacy in SMA. Three adult SMA 3a patients under treatment with nusinersen underwent longitudinal clinical and qMRI examinations every 4 months from baseline to 21-month follow-up. The qMRI protocol aimed to quantify thigh muscle fat fraction (FF) and water-T2 (w-T2) and to characterize SC volumes and microstructure. Eleven healthy controls underwent the same SC protocol (single time point). We evaluated clinical and imaging outcomes of SMA patients longitudinally and compared SC data between groups transversally. Patient motor function was stable, with only Patient 2 showing moderate improvements. Average muscle FF was already high at baseline (50%) and progressed over time (57%). w-T2 was also slightly higher than previously published data at baseline and slightly decreased over time. Cross-sectional area of the whole SC, gray matter (GM), and ventral horns (VHs) of Patients 1 and 3 were reduced compared to controls and remained stable over time, while GM and VHs areas of Patient 2 slightly increased. We found altered diffusion and magnetization transfer parameters in SC structures of SMA patients compared to controls, thus suggesting changes in tissue microstructure and myelin content. In this pilot study, we found a progression of FF in thigh muscles of SMA 3a patients during nusinersen therapy and a concurrent slight reduction of w-T2 over time. The SC qMRI analysis confirmed previous imaging and histopathological studies suggesting degeneration of αMN of the VHs, resulting in GM atrophy and demyelination. Our longitudinal data suggest that qMRI could represent a feasible technique for capturing microstructural changes induced by SMA and a candidate methodology for monitoring the effects of treatment, once replicated on a larger cohort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.613834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039452PMC
March 2021

Nutrition and Exercise in a Case of Carnitine Palmitoyl-Transferase II Deficiency.

Front Physiol 2021 17;12:637406. Epub 2021 Mar 17.

Criams-Sport Medicine Centre Voghera, University of Pavia, Pavia, Italy.

In the mild subtype of inherited carnitine palmitoyltransferase II (CPTII) deficiency, muscular mitochondrial fatty acid β-oxidation is impaired. In this condition, interventions involve daily dietary restriction of fats and increase of carbohydrates, whereas physical exercise is commonly contraindicated due to the risk of muscle pain and rhabdomyolysis. We present the case of a 14-year-old female with CPTII deficiency who underwent a 1-h session of unsupervised exercise training for 6 months, 3 days per week, including interval and resistance exercises, after diet assessment and correction. Before and after intervention, the resting metabolic rate (RMR) and respiratory quotient (RQ) were measured by indirect calorimetry, and a cardiopulmonary exercise test (CPET, 10 W/30 s to exhaustion) was performed. Interval training consisted of a 1 min run and a 5 min walk (for 15 min progressively increased to 30 min). During these efforts, the heart rate was maintained over 70% HR max corresponding to respiratory exchange ratio (RER) of 0.98. Resistance training included upper/lower split workouts (3 sets of 8 repetitions each, with 2 min rest between sets). Blood CK was checked before and 36 h after two training sessions chosen randomly without significant difference. After training, RMR increased (+8.1%) and RQ lowered into the physiological range (from 1.0 to 0.85). CPET highlighted an increase of peak power output (+16.7%), aerobic performance (VO peak, 8.3%) and anaerobic threshold (+5.7%), oxygen pulse (+4.5%) and a much longer isocapnic buffering duration (+335%). No muscle pain or rhabdomyolysis was reported. Results from our study highlight that training based on short-duration high-intensity exercise improves overall metabolism and aerobic fitness, thus being feasible, at least in a case of CPTII deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.637406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009997PMC
March 2021

The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy.

Neuromuscul Disord 2021 Jun 21;31(6):479-488. Epub 2021 Feb 21.

Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy; Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, Rome 00152, Italy. Electronic address:

The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5' (upstream) and 3' (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3' adjacent nucleotide ("stop+4 model") was considered (p < 0.05) with patients with stop codon TGA and 3' adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nmd.2021.02.015DOI Listing
June 2021

Increased resistance towards fatigability in patients with facioscapulohumeral muscular dystrophy.

Eur J Appl Physiol 2021 Jun 1;121(6):1617-1629. Epub 2021 Mar 1.

Criams-Sport Medicine Centre Voghera, University of Pavia, Voghera, Italy.

Purpose: In facioscapulohumeral muscular dystrophy (FSHD) fatigue is a major complaint. We aimed to investigate whether during isometric sustained elbow flexions, performance fatigability indexes differ in patients with FSHD with respect to healthy controls.

Methods: Seventeen patients with FSHD and seventeen healthy controls performed two isometric flexions of the dominant biceps brachii at 20% of their maximal voluntary contraction (MVC) for 2 min and then at 60% MVC until exhaustion. Muscle weakness was characterized as a percentage of predicted values. Maximal voluntary strength, endurance time and performance fatigability indices (mean frequency of the power spectrum (MNF), muscle fiber conduction velocity (CV) and fractal dimension (FD)), extracted from the surface electromyogram signal (sEMG) were compared between the two groups.

Results: In patients with FSHD, maximal voluntary strength was 68.7% of predicted value (p < 0.01). Compared to healthy controls, FSHD patients showed reduced MVC (p < 0.001; r = 0.62) and lower levels of performance fatigability, characterized by reduced rate of changes in MNF (p < 0.01; r = 0.56), CV (p < 0.05; 0.37) and FD (p < 0.001; r = 0.51) and increased endurance time (p < 0.001; r = 0.63), during the isometric contraction at 60% MVC.

Conclusion: A decreased reduction in the slopes of all the considered sEMG parameters during sustained isometric elbow flexions suggests that patients with FSHD experience lower levels of performance fatigability compared to healthy controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00421-021-04650-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144151PMC
June 2021

Large genotype-phenotype study in carriers of D4Z4 borderline alleles provides guidance for facioscapulohumeral muscular dystrophy diagnosis.

Sci Rep 2020 12 10;10(1):21648. Epub 2020 Dec 10.

Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Facioscapulohumeral muscular dystrophy (FSHD) is a myopathy with prevalence of 1 in 20,000. Almost all patients affected by FSHD carry deletions of an integral number of tandem 3.3 kilobase repeats, termed D4Z4, located on chromosome 4q35. Assessment of size of D4Z4 alleles is commonly used for FSHD diagnosis. However, the extended molecular testing has expanded the spectrum of clinical phenotypes. In particular, D4Z4 alleles with 9-10 repeat have been found in healthy individuals, in subjects with FSHD or affected by other myopathies. These findings weakened the strict relationship between observed phenotypes and their underlying genotypes, complicating the interpretation of molecular findings for diagnosis and genetic counseling. In light of the wide clinical variability detected in carriers of D4Z4 alleles with 9-10 repeats, we applied a standardized methodology, the Comprehensive Clinical Evaluation Form (CCEF), to describe and characterize the phenotype of 244 individuals carrying D4Z4 alleles with 9-10 repeats (134 index cases and 110 relatives). The study shows that 54.5% of index cases display a classical FSHD phenotype with typical facial and scapular muscle weakness, whereas 20.1% present incomplete phenotype with facial weakness or scapular girdle weakness, 6.7% display minor signs such as winged scapula or hyperCKemia, without functional motor impairment, and 18.7% of index cases show more complex phenotypes with atypical clinical features. Family studies revealed that 70.9% of relatives carrying 9-10 D4Z4 reduced alleles has no motor impairment, whereas a few relatives (10.0%) display a classical FSHD phenotype. Importantly all relatives of index cases with no FSHD phenotype were healthy carriers. These data establish the low penetrance of D4Z4 alleles with 9-10 repeats. We recommend the use of CCEF for the standardized clinical assessment integrated by family studies and further molecular investigation for appropriate diagnosis and genetic counseling. Especially in presence of atypical phenotypes and/or sporadic cases with all healthy relatives is not possible to perform conclusive diagnosis of FSHD, but all these cases need further studies for a proper diagnosis, to search novel causative genetic defects or investigate environmental factors or co-morbidities that may trigger the pathogenic process. These evidences are also fundamental for the stratification of patients eligible for clinical trials. Our work reinforces the value of large genotype-phenotype studies to define criteria for clinical practice and genetic counseling in rare diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-78578-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730397PMC
December 2020

Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3.

J Neurol Neurosurg Psychiatry 2020 11 11;91(11):1166-1174. Epub 2020 Sep 11.

Department of Neurology/Stroke Unit, Bolzano Hospital, Bolzano, Trentino-Alto Adige, Italy.

Objective: To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA).

Methods: Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6).

Results: We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18-72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14.

Conclusions: Our data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2020-323822DOI Listing
November 2020

Estimating the impact of COVID-19 pandemic on services provided by Italian Neuromuscular Centers: an Italian Association of Myology survey of the acute phase.

Acta Myol 2020 Jun 1;39(2):57-66. Epub 2020 Jun 1.

Child and Adolescent Unit, IRCCS Mondino Foundation, Pavia, Italy.

Introduction: Since February 2020, the outbreak of COVID-19 in Italy has forced the health care system to undergo profound rearrangements in its services and facilities, especially in the worst-hit areas in Northern Italy. In this setting, inpatient and outpatient services had to rethink and reorganize their activities to meet the needs of patients during the "lockdown". The Italian Association of Myology developed a survey to estimate the impact of these changes on patients affected by neuromuscular disorders and on specialized neuromuscular centers during the acute phase of COVID-19 pandemic.

Methods: We developed an electronic survey that was sent to neuromuscular centers affiliated with the Italian Association of Myology, assessing changes in pharmacological therapies provision, outpatient clinical and instrumental services, support services (physiotherapy, nursing care, psychological support) and clinical trials.

Results: 40% of surveyed neuromuscular centers reported a reduction in outpatient visit and examinations (44.5% of centers in Northern regions; 25% of centers in Central regions; 50% of centers in Southern regions). Twenty-two% of centers postponed in-hospital administration of therapies for neuromuscular diseases (23.4% in Northern regions; 13.0% in Central regions; 20% in Southern regions). Diagnostic and support services (physiotherapy, nursing care, psychological support) were suspended in 57% of centers (66/43/44% in Northern, Central and Southern centers respectively) Overall, the most affected services were rehabilitative services and on-site outpatient visits, which were suspended in 93% of centers. Strategies adopted by neuromuscular centers to overcome these changes included maintaining urgent on-site visits, addressing patients to available services and promoting remote contact and telemedicine.

Conclusions: Overall, COVID-19 pandemic resulted in a significant disruption of clinical and support services for patients with neuromuscular diseases. Despite the efforts to provide telemedicine consults to patients, this option could be promoted and improved further. A close collaboration between the different neuromuscular centers and service providers as well as further implementation of telehealth platforms are necessary to ensure quality care to NMD patients in the near future and in case of recurrent pandemic waves.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.36185/2532-1900-008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460733PMC
June 2020

A 5-year clinical follow-up study from the Italian National Registry for FSHD.

J Neurol 2021 Jan 19;268(1):356-366. Epub 2020 Aug 19.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, via G. Campi 287, 41125, Modena, Italy.

Background: The natural history of facioscapulohumeral muscular dystrophy (FSHD) is undefined.

Methods: An observational cohort study was conducted in 246 FSHD1 patients. We split the analysis between index cases and carrier relatives and we classified all patients using the Comprehensive Clinical Evaluation Form (CCEF). The disease progression was measured as a variation of the FSHD score performed at baseline and at the end of 5-year follow-up (ΔFSHD score).

Findings: Disease worsened in 79.4% (112/141) of index cases versus 38.1% (40/105) of carrier relatives and advanced more rapidly in index cases (ΔFSHD score 2.3 versus 1.2). The 79.1% (38/48) of asymptomatic carriers remained asymptomatic. The highest ΔFSHD score (1.7) was found in subject with facial and scapular weakness at baseline (category A), whereas in subjects with incomplete phenotype (facial or scapular weakness, category B) had lower ΔFSHD score (0.6) p < 0.0001.

Conclusions: The progression of disease is different between index cases and carrier relatives and the assessment of the CCEF categories has strong prognostic effect in FSHD1 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-020-10144-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815626PMC
January 2021

Phenotypic Variability Among Patients With D4Z4 Reduced Allele Facioscapulohumeral Muscular Dystrophy.

JAMA Netw Open 2020 05 1;3(5):e204040. Epub 2020 May 1.

Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Importance: Facioscapulohumeral muscular dystrophy (FSHD) is considered an autosomal dominant disorder, associated with the deletion of tandemly arrayed D4Z4 repetitive elements. The extensive use of molecular analysis of the D4Z4 locus for FSHD diagnosis has revealed wide clinical variability, suggesting that subgroups of patients exist among carriers of the D4Z4 reduced allele (DRA).

Objective: To investigate the clinical expression of FSHD in the genetic subgroup of carriers of a DRA with 7 to 8 repeat units (RUs).

Design, Setting, And Participants: This multicenter cross-sectional study included 422 carriers of DRA with 7 to 8 RUs (187 unrelated probands and 235 relatives) from a consecutive sample of 280 probands and 306 relatives from the Italian National Registry for FSHD collected between 2008 and 2016. Participants were evaluated by the Italian Clinical Network for FSHD, and all clinical and molecular data were collected in the Italian National Registry for FSHD database. Data analysis was conducted from January 2017 to June 2018.

Main Outcomes And Measures: The phenotypic classification of probands and relatives was obtained by applying the Comprehensive Clinical Evaluation Form which classifies patients in the 4 following categories: (1) participants presenting facial and scapular girdle muscle weakness typical of FSHD (category A, subcategories A1-A3), (2) participants with muscle weakness limited to scapular girdle or facial muscles (category B, subcategories B1 and B2), (3) asymptomatic or healthy participants (category C, subcategories C1 and C2), and (4) participants with myopathic phenotypes presenting clinical features not consistent with FSHD canonical phenotype (category D, subcategories D1 and D2).

Results: A total of 187 probands (mean [SD] age at last neurological examination, 53.5 [15.2] years; 103 [55.1%] men) and 235 relatives (mean [SD] age at last neurologic examination, 45.1 [17.0] years; 104 [44.7%] men) with a DRA with 7 to 8 RUs and a molecular diagnosis of FSHD were evaluated. Of 187 probands, 99 (52.9%; 95% CI, 45.7%-60.1%) displayed the classic FSHD phenotype, whereas 86 (47.1%; 95% CI, 39.8%-54.3%) presented incomplete or atypical phenotypes. Of 235 carrier relatives from 106 unrelated families, 124 (52.8%; 95% CI, 46.4%-59.7%) had no motor impairment, whereas a small number (38 [16.2%; 95% CI, 9.8%-23.1%]) displayed the classic FSHD phenotype, and 73 (31.0%; 95% CI, 24.7%-38.0%) presented with incomplete or atypical phenotypes. In 37 of 106 families (34.9%; 95% CI, 25.9%-44.8%), the proband was the only participant presenting with a myopathic phenotype, while only 20 families (18.9%; 95% CI, 11.9%-27.6%) had a member with autosomal dominant FSHD.

Conclusions And Relevance: This study found large phenotypic variability associated with individuals carrying a DRA with 7 to 8 RUs, in contrast to the indication that a positive molecular test is the only determining aspect for FSHD diagnosis. These findings suggest that carriers of a DRA with 7 to 8 RUs constitute a genetic subgroup different from classic FSHD. Based on these results, it is recommended that clinicians use the Comprehensive Clinical Evaluation Form for clinical classification and, whenever possible, study the extended family to provide the most adequate clinical management and genetic counseling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.4040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195625PMC
May 2020

Genetic modifiers of respiratory function in Duchenne muscular dystrophy.

Ann Clin Transl Neurol 2020 05 28;7(5):786-798. Epub 2020 Apr 28.

Neuromuscular Center, AOU Città della Salute e della Scienza, University of Torino, Turin, Italy.

Objective: Respiratory insufficiency is a major complication of Duchenne muscular dystrophy (DMD). Its progression shows considerable interindividual variability, which has been less thoroughly characterized and understood than in skeletal muscle. We collected pulmonary function testing (PFT) data from a large retrospective cohort followed at Centers collaborating in the Italian DMD Network. Furthermore, we analyzed PFT associations with different DMD mutation types, and with genetic variants in SPP1, LTBP4, CD40, and ACTN3, known to modify skeletal muscle weakness in DMD. Genetic association findings were independently validated in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS).

Methods And Results: Generalized estimating equation analysis of 1852 PFTs from 327 Italian DMD patients, over an average follow-up time of 4.5 years, estimated that forced vital capacity (FVC) declined yearly by -4.2%, forced expiratory volume in 1 sec by -5.0%, and peak expiratory flow (PEF) by -2.9%. Glucocorticoid (GC) treatment was associated with higher values of all PFT measures (approximately + 15% across disease stages). Mutations situated 3' of DMD intron 44, thus predicted to alter the expression of short dystrophin isoforms, were associated with lower (approximately -6%) PFT values, a finding independently validated in the CINRG-DNHS. Deletions amenable to skipping of exon 51 and 53 were independently associated with worse PFT outcomes. A meta-analysis of the two cohorts identified detrimental effects of SPP1 rs28357094 and CD40 rs1883832 minor alleles on both FVC and PEF.

Interpretation: These findings support GC efficacy in delaying respiratory insufficiency, and will be useful for the design and interpretation of clinical trials focused on respiratory endpoints in DMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.51046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261745PMC
May 2020

Interpretation of the Epigenetic Signature of Facioscapulohumeral Muscular Dystrophy in Light of Genotype-Phenotype Studies.

Int J Mol Sci 2020 Apr 10;21(7). Epub 2020 Apr 10.

Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by incomplete penetrance and intra-familial clinical variability. The disease has been associated with the genetic and epigenetic features of the D4Z4 repetitive elements at 4q35. Recently, D4Z4 hypomethylation has been proposed as a reliable marker in the FSHD diagnosis. We exploited the Italian Registry for FSHD, in which FSHD families are classified using the Clinical Comprehensive Evaluation Form (CCEF). A total of 122 index cases showing a classical FSHD phenotype (CCEF, category A) and 110 relatives were selected to test with the receiver operating characteristic (ROC) curve, the diagnostic and predictive value of D4Z4 methylation. Moreover, we performed DNA methylation analysis in selected large families with reduced penetrance characterized by the co-presence of subjects carriers of one D4Z4 reduced allele with no signs of disease or presenting the classic FSHD clinical phenotype. We observed a wide variability in the D4Z4 methylation levels among index cases revealing no association with clinical manifestation or disease severity. By extending the analysis to family members, we revealed the low predictive value of D4Z4 methylation in detecting the affected condition. In view of the variability in D4Z4 methylation profiles observed in our large cohort, we conclude that D4Z4 methylation does not mirror the clinical expression of FSHD. We recommend that measurement of this epigenetic mark must be interpreted with caution in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21072635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178248PMC
April 2020

Psychosocial impact of sport activity in neuromuscular disorders.

Neurol Sci 2020 Sep 4;41(9):2561-2567. Epub 2020 Apr 4.

Nemo Sud Clinical Centre for Neuromuscular Disorders, Messina, Italy.

Previous studies demonstrated the benefits of motor exercise and physical activity in neuromuscular disorders. However, very few papers assessed the effects of sport practise. The aim of this multicentre study was to assess the impact of sport activity on self-esteem and emotional regulation in a cohort of athletes with neuromuscular disorders. The 38 patients with Duchenne, Becker or other types of muscular dystrophy or spinal muscular atrophy practising sport (aged 13-49 years) and 39 age-, gender-, disability- and disease-matched patients not practising sport were enrolled. Testing procedures to assess self-esteem, anxiety and depression disorder, personality trait and quality of life (QoL) were used. Patients practising sport had a significantly higher self-esteem, lower level of depression, greater social own identity and adherence and QoL. Frequency of sport activity may represent a complementary therapy in neuromuscular disorders to improve mental and social well-being.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-020-04345-1DOI Listing
September 2020

The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study.

Front Genet 2020 3;11:131. Epub 2020 Mar 3.

Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Dystrophinopathies are inherited diseases caused by mutations in the dystrophin () gene for which testing is mandatory for genetic diagnosis, reproductive choices and eligibility for personalized trials. We genotyped the gene in our Italian cohort of 1902 patients (BMD n = 740, 39%; DMD n =1162, 61%) within a nationwide study involving 11 diagnostic centers in a 10-year window (2008-2017). In DMD patients, we found deletions in 57%, duplications in 11% and small mutations in 32%. In BMD, we found deletions in 78%, duplications in 9% and small mutations in 13%. In BMD, there are a higher number of deletions, and small mutations are more frequent than duplications. Among small mutations that are generally frequent in both phenotypes, 44% of DMD and 36% of BMD are nonsense, thus, eligible for stop codon read-through therapy; 63% of all out-of-frame deletions are eligible for single exon skipping. Patients were also assigned to Italian regions and showed interesting regional differences in mutation distribution. The full genetic characterization in this large, nationwide cohort has allowed us to draw several correlations between DMD/BMD genotype landscapes and mutation frequency, mutation types, mutation locations along the gene, exon/intron architecture, and relevant protein domain, with effects on population genetic characteristics and new personalized therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.00131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063120PMC
March 2020

Physiological aspects of muscular adaptations to training translated to neuromuscular diseases.

Acta Myol 2019 Dec 1;38(4):197-206. Epub 2019 Dec 1.

CRIAMS-Sport Medicine Centre, University of Pavia, Voghera, Italy.

The high level of complexity underlying the heterogeneous pathophysiology of neuromuscular diseases is a fundamental limiting factor in understanding the role of physical activity in their onset and/or clinical evolution. To overcome this difficulty, it is essential to rely on and deep knowledge of the aetiology and on the physiological adaptations to physical exercise, in order to predict how they can impact on the clinical history of each disease. This paper illustrates the possible strategies of intervention in some neuromuscular disorders, through the analysis of their supposed pathogenic mechanisms. Nevertheless, no clear conclusions can be inferred so far.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955633PMC
December 2019

MRI patterns of muscle involvement in type 2 and 3 spinal muscular atrophy patients.

J Neurol 2020 Apr 27;267(4):898-912. Epub 2019 Nov 27.

Pediatric Neurology, Università Cattolica del Sacro Cuore, Largo Gemelli 8, 00168, Rome, Italy.

Only few studies have reported muscle involvement in spinal muscular atrophy using muscle MRI but this has not been systematically investigated in a large cohort of both pediatric and adult patients with type 2 and type 3 spinal muscular atrophy. The aim of the present study was to define possible patterns of muscle involvement on MRI, assessing both fatty replacement and muscle atrophy, in a cohort of type 2 and type 3 spinal muscular atrophy children and adults (age range 2-45 years), including both ambulant and non-ambulant patients. Muscle MRI protocol consisted in T1-weighted sequences acquired on axial plane covering the pelvis, the thigh, and the leg with contiguous slices. Each muscle was examined through its whole extension using a grading system that allows a semiquantitative evaluation of fatty infiltration. Thigh muscles were also grouped in anterior, posterior, and medial compartment for classification of global atrophy. The results showed a large variability in both type 2 and type 3 spinal muscular atrophy, with a various degree of proximal to distal gradient. Some muscles, such us the adductor longus and gracilis were always selectively spared. In all patients, the involvement was a combination of muscle atrophy and muscle infiltration. The variability observed may help to better understand both natural history and response to new treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-019-09646-wDOI Listing
April 2020

Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype.

Neurol Neuroimmunol Neuroinflamm 2020 01 21;7(1). Epub 2019 Nov 21.

From the Department of Brain and Behavioral Sciences (A.C., I.C., G.C., R.C., E.V.), University of Pavia, Pavia, Italy; Department of Neuromuscular Disease (A.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Neuroalgology Unit (R.L., P.D., L.P., G.L.), IRCCS Fondazione Istituto Neurologico "Carlo Besta," Milan, Italy; Department of Neurosciences (C.B., M.R., A.S.), University of Padova, Padova, Italy; IRCCS Mondino Foundation (I.C., G.C., E.Z., R.C., M.G., E.V., E.A., A.B., D.F.), Pavia, Italy; Department of Neuroscience (L.B., C.D.M., A.S.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino (L.B., C.D.M., A.S.), Genova, Italy; Department of Neurosciences (F.M., E.S., A.T.), Odontostomatological and Reproductive Sciences, University of Naples "Federico II," Naples, Italy; Fondazione Policlinico Universitario Agostino Gemelli-IRCCS. UOC Neurologia (M.L., A.R., M.S.), Rome, Italy; Università Cattolica del Sacro Cuore (M.L., A.R., M.S.), Rome, Italy; Section of Neurology (S.F., S.M.), Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; Department of Neurology and Stroke Unit (A.M.C.), Ospedale di Circolo/Fondazione Macchi, Varese, Italy; Department of Systems Medicine (G.A.M., G.M.), University of Rome Tor Vergata, Rome, Italy; Neurological Department (A.R.), ASST Lecco; Ospedale Treviglio ASST Bergamo Ovest (M.C.), Italy; Department of Neurology (R.F., F.C.), San Raffaele Scientific Institute, Milan, Italy; Department of Neurorehabilitation Sciences (M.C.), Casa Cura Policlinico (CCP), Milan, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Messina, Messina, Italy; Department of Medicine, Surgery and Neurosciences (F.G.), University of Siena, Italy; Referral Center for Neuromuscular Diseases and ALS (L.K., E.M.), AP-HM, Timone University Hospital, Marseille, France; Université de Bordeaux (C.M.), Interdisciplinary Institute for Neuroscience, Bordeaux, France; Humanitas Clinical and Research Center (C.G., P.D., E.N.-O.), Milan University, Milan, Italy; IRCCS Centro Neurolesi "Bonino Pulejo" (C.S.), Messina, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco" (G.B., G.L.), University of Milan, Milan, Italy; and Institute for Neurosciences of Montpellier (J.D.), INSERM U1051, Montpellier University, Hopital Saint Eloi, Montpellier, France.

Objective: To assess the prevalence and isotypes of anti-nodal/paranodal antibodies to nodal/paranodal proteins in a large chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort, compare clinical features in seronegative vs seropositive patients, and gather evidence of their isotype-specific pathogenic role.

Methods: Antibodies to neurofascin-155 (Nfasc155), neurofascin-140/186 (Nfasc140/186), contactin-1 (CNTN1), and contactin-associated protein 1 (Caspr1) were detected with ELISA and/or cell-based assay. Antibody pathogenicity was tested by immunohistochemistry on skin biopsy, intraneural injection, and cell aggregation assay.

Results: Of 342 patients with CIDP, 19 (5.5%) had antibodies against Nfasc155 (n = 9), Nfasc140/186 and Nfasc155 (n = 1), CNTN1 (n = 3), and Caspr1 (n = 6). Antibodies were absent from healthy and disease controls, including neuropathies of different causes, and were mostly detected in patients with European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite CIDP (n = 18). Predominant antibody isotypes were immunoglobulin G (IgG)4 (n = 13), IgG3 (n = 2), IgG1 (n = 2), or undetectable (n = 2). IgG4 antibody-associated phenotypes included onset before 30 years, severe neuropathy, subacute onset, tremor, sensory ataxia, and poor response to intravenous immunoglobulin (IVIG). Immunosuppressive treatments, including rituximab, cyclophosphamide, and methotrexate, proved effective if started early in IVIG-resistant IgG4-seropositive cases. Five patients with an IgG1, IgG3, or undetectable isotype showed clinical features indistinguishable from seronegative patients, including good response to IVIG. IgG4 autoantibodies were associated with morphological changes at paranodes in patients' skin biopsies. We also provided preliminary evidence from a single patient about the pathogenicity of anti-Caspr1 IgG4, showing their ability to penetrate paranodal regions and disrupt the integrity of the Nfasc155/CNTN1/Caspr1 complex.

Conclusions: Our findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment.

Classification Of Evidence: This study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/NXI.0000000000000639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935837PMC
January 2020

Longitudinal natural history in young boys with Duchenne muscular dystrophy.

Neuromuscul Disord 2019 11 26;29(11):857-862. Epub 2019 Sep 26.

Paediatric Neurology, Catholic University, Rome, Italy; Centro Clinico Nemo, Policlinico Gemelli, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nmd.2019.09.010DOI Listing
November 2019

Subcutaneous Immunoglobulin in Infantile Chronic Inflammatory Demyelinating Polyneuropathy: A Case Report.

J Pediatr Neurosci 2019 Jan-Mar;14(1):38-41

Woman and Child Department, Ospedale "F. Del Ponte," University of Insubria, Varese, Italy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronically progressive or relapsing sensorimotor disorder presumably due to antibody-mediated reactions. It is a rare condition in children, with estimated prevalence as 0.48 per 100,000 among patients younger than 20 years of age. Recommended treatments include immune modulators, intravenous immunoglobulins (IVIgs), steroids, and plasmapheresis. Management of pediatric CIDP is challenging because of the lack of evidence-based efficacy of the current therapies in children. Because of the rarity of this condition, there are no double-blind randomized studies to support the therapeutic choice as well as to identify the optimal first-line therapeutic regimen. IVIgs are widely used but the intravenous administration is usually uncomfortable, especially for children. Subcutaneous immunoglobulins (SCIgs) have proven to be effective in adults with CIDP and in children affected by antibody deficiencies and other different immune and inflammatory disorders. Herein, we described the case of a 7-year-old boy, affected by CIDP who clinically responded to IVIg but was dependent on this therapy. In order to improve his quality of life, we switched to SCIg with excellent result.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jpn.JPN_132_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601112PMC
July 2019

Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53.

PLoS One 2019 25;14(6):e0218683. Epub 2019 Jun 25.

Pediatric Neurology, Department of Woman and Child Health and Public Health, Child Health Area, Università Cattolica del Sacro Cuore, Rome, Italy.

Introduction: The aim of this international collaborative effort was to report 36-month longitudinal changes using the 6MWT in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53.

Materials And Methods: Of the 92 patients included in the study, 24 had deletions amenable to skip exon 44, 27 exon 45, 18 exon 51, and 28 exon 53. Five patients with a single deletion of exon 52 were counted in both subgroups skipping exon 51 and 53.

Results: The difference between subgroups amenable to skip different exons was not significant at 12 months but became significant at both 24 (p≤0.05) and 36 months (p≤0.01).

Discussion: Mutations amenable to skip exon 53 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had better results both at baseline and at follow up. Deletions amenable to skip exon 45 were associated with a more variable pattern of progression. Single exon deletions were more often associated with less drastic changes but this was not always true in individual cases.

Conclusion: Our results confirm that the progression of disease can differ between patients with different deletions, although the changes only become significant from 24 months onwards. This information is relevant because there are current clinical trials specifically targeting patients with these subgroups of mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218683PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592545PMC
February 2020

Value of structured reporting in neuromuscular disorders.

Radiol Med 2019 Jul 9;124(7):628-635. Epub 2019 Mar 9.

Neuroradiology Department, IRCCS C. Mondino Foundation, Pavia, Italy.

Objective: To assess whether structured reports (SRs) of MRI in patients with inherited neuromuscular disorders (IND) provide more clinically relevant information than non-structured reports (NSRs) and whether neuroradiologists' expertise affects completeness of reports.

Material And Methods: Lower limbs' MRI reports of patients with IND produced by neuroradiologists with different level of expertise (> 15 years vs. < 15 years of experience in reading IND-MRI) before and after implementation of a SR template were included. Reports were assessed for the presence of 9 key features relevant for IND management. Reports and images were evaluated by neurologists who assessed: disease-specific muscular involvement pattern; presence of sufficient information to order the appropriate genetic/diagnostic tests; presence of sufficient information to make therapeutic decision/perform biopsy and necessity to review MRI images. Mann-Whitney and Fisher's exact tests were used to compare the number of key features for NSR and SR and neurologists' answers for reports produced by neuroradiologists with different experience.

Results: Thirty-one SRs and 101 NSRs were reviewed. A median of 8 and 6 key features was present in SR and NSR, respectively (p value < 0.0001). When reports were produced by less expert neuroradiologists, neurologists recognized muscular involvement pattern, had sufficient information for clinical decision-making/perform biopsy more often with SR than NSR (p values: < 0.0001), and needed to evaluate images less often with SR (p value: 0.0001). When reports produced by expert neuroradiologists were evaluated, no significant difference in neurologists' answers was observed.

Conclusion: SR of IND-MRI contained more often clinically relevant information considered important for disease management than NSR. Radiologist's expertise affects completeness of NSR reports.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11547-019-01012-0DOI Listing
July 2019

Advances in Quantitative Imaging of Genetic and Acquired Myopathies: Clinical Applications and Perspectives.

Front Neurol 2019 11;10:78. Epub 2019 Feb 11.

Unit of Neurology, Center for Neuromuscular Diseases, ASST Spedali Civili and University of Brescia, Brescia, Italy.

In the last years, magnetic resonance imaging (MRI) has become fundamental for the diagnosis and monitoring of myopathies given its ability to show the severity and distribution of pathology, to identify specific patterns of damage distribution and to properly interpret a number of genetic variants. The advances in MR techniques and post-processing software solutions have greatly expanded the potential to assess pathological changes in muscle diseases, and more specifically of myopathies; a number of features can be studied and quantified, ranging from composition, architecture, mechanical properties, perfusion, and function, leading to what is known as quantitative MRI (qMRI). Such techniques can effectively provide a variety of information beyond what can be seen and assessed by conventional MR imaging; their development and application in clinical practice can play an important role in the diagnostic process and in assessing disease course and treatment response. In this review, we briefly discuss the current role of muscle MRI in diagnosing muscle diseases and describe in detail the potential and perspectives of the application of advanced qMRI techniques in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2019.00078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378279PMC
February 2019

Functional assessment tools in children with Pompe disease: A pilot comparative study to identify suitable outcome measures for the standard of care.

Eur J Paediatr Neurol 2018 Nov 18;22(6):1103-1109. Epub 2018 Aug 18.

Department of Neuroscience, Division of Neurology and Neuromuscular Diseases, Turin University Hospital, Corso Bramante 88/90, 10126, Turin, Italy.

Background: Pompe disease (PD) is a rare condition caused by mutations in gene encoding for the enzyme alpha-glucosidase, resulting in an abnormal intracellular accumulation of glycogen. The disease clinical spectrum ranges from severe infantile forms to adult-onset forms with minor limitations. Since 2000 enzyme replacement therapy (ERT) is available and disease natural history has changed, with prolonged survival and evidence of myopathic features.

Methods: In this study, we monitored disease progression up to three years in eight young patients with PD. Based on the literature data and the long term personal experience, we selected validated functional scales for neuromuscular disorders and compared the results to identify a simple and reliable protocol for the follow-up of children with PD. Moreover, we evaluated cognitive functions using developmental/cognitive tests.

Results: Based on study results, we suggest that motor functions in children with PD could be better assessed by Chop Intend, MFM20 (Motor Function Measure Scale for Neuromuscular Diseases 20) and NSAA (North Star Ambulatory Assessment), according to age and functional level. Evaluation should be completed with ROM (Range Of Motion) measurement, MRC (Medical Research Council) evaluation and 6MWT (6 Minute Walk test) when possible.

Conclusions: The proposed protocol seems to be reliable and should be done every six months, because of the progressive natural history of the disease, the rapid changes typical of developmental age and the need to document ERT effects. About cognitive functions, additional tests to classical intelligence scales (WISC, WPPSI) should be useful to better describe specific neuropsychological profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2018.08.001DOI Listing
November 2018

Upper limb function in Duchenne muscular dystrophy: 24 month longitudinal data.

PLoS One 2018 20;13(6):e0199223. Epub 2018 Jun 20.

Department of Neurosciences, University of Padua, Padua, Italy.

The aim of the study was to establish 24 month changes in upper limb function using a revised version of the performance of upper limb test (PUL 2.0) in a large cohort of ambulant and non-ambulant boys with Duchenne muscular dystrophy and to identify possible trajectories of progression. Of the 187 patients studied, 87 were ambulant (age range: 7-15.8 years), and 90 non-ambulant (age range: 9.08-24.78). The total scores changed significantly over time (p<0.001). Non-ambulant patients had lower total scores at baseline (mean 19.7) when compared to the ambulant ones (mean 38.4). They also had also a bigger decrease in total scores over 24 months compared to the ambulant boys (4.36 vs 2.07 points). Multivariate model analysis showed that the Performance of Upper Limb changes reflected the entry level and ambulation status, that were independently associated to the slope of Performance of Upper Limb changes. This information will be of help both in clinical practice and at the time of designing clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199223PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010252PMC
April 2019

Muscle ultrasound elastography and MRI in preschool children with Duchenne muscular dystrophy.

Neuromuscul Disord 2018 06 13;28(6):476-483. Epub 2018 Apr 13.

Institute of Radiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

The aim of this study was to determine muscle tissue elasticity, measured with shear-wave elastography, in selected lower limb muscles of patients affected by Duchenne muscular dystrophy (DMD) and to correlate the values obtained with those recorded in healthy children and with muscle magnetic resonance imaging (MRI) data from the same DMD children, specifically the pattern on T1-weighted (w) and short-tau inversion recovery (STIR) sequences. Five preschool DMD children and five age-matched healthy children were studied with shear-wave elastography. In the DMD children, muscle stiffness was moderately higher compared with the muscle stiffness in HC, in the rectus femoris, vastus lateralis, adductor magnus and gluteus maximus muscles. On muscle MRI T1-w images showed fatty replacement in 3/5 patients at the level of the GM, while thigh and leg muscles were affected in 2/5; hyperintensity on STIR images was identified in 4/5 patients. No significant correlation was observed between stiffness values and MRI scoring. Our study demonstrated that lower limb muscles of preschool DMD patients show fatty replacement and patchy edema on muscle MRI and increased stiffness on shear-wave elastography. In conclusion, although further studies in larger cohorts are needed, shear-wave elastography could be considered a useful non-invasive tool to easily monitor muscle changes in early stages of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nmd.2018.02.007DOI Listing
June 2018

MRI in sarcoglycanopathies: a large international cohort study.

J Neurol Neurosurg Psychiatry 2018 01 9;89(1):72-77. Epub 2017 Sep 9.

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK.

Objectives: To characterise the pattern and spectrum of involvement on muscle MRI in a large cohort of patients with sarcoglycanopathies, which are limb-girdle muscular dystrophies (LGMD2C-2F) caused by mutations in one of the four genes coding for muscle sarcoglycans.

Methods: Lower limb MRI scans of patients with LGMD2C-2F, ranging from severe childhood variants to milder adult-onset forms, were collected in 17 neuromuscular referral centres in Europe and USA. Muscle involvement was evaluated semiquantitatively on T1-weighted images according to a visual score, and the global pattern was assessed as well.

Results: Scans from 69 patients were examined (38 LGMD2D, 18 LGMD2C, 12 LGMD2E and 1 LGMD2F). A common pattern of involvement was found in all the analysed scans irrespective of the mutated gene. The most and earliest affected muscles were the thigh adductors, glutei and posterior thigh groups, while lower leg muscles were relatively spared even in advanced disease. A proximodistal gradient of involvement of vasti muscles was a consistent finding in these patients, including the most severe ones.

Conclusions: Muscle involvement on MRI is consistent in patients with LGMD2C-F and can be helpful in distinguishing sarcoglycanopathies from other LGMDs or dystrophinopathies, which represent the most common differential diagnoses. Our data provide evidence about selective susceptibility or resistance to degeneration of specific muscles when one of the sarcoglycans is deficient, as well as preliminary information about progressive involvement of the different muscles over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2017-316736DOI Listing
January 2018
-->