34 results on '"Federica Montagnese"'
Search Results
2. 268th ENMC workshop - Genetic diagnosis, clinical classification, outcome measures, and biomarkers in Facioscapulohumeral Muscular Dystrophy (FSHD): Relevance for clinical trials
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Federica Montagnese, Katy de Valle, Richard J.L.F. Lemmers, Karlien Mul, Julie Dumonceaux, Nicol Voermans, Giorgio Tasca, Maria Gomez-Rodulfo, Sabrina Sacconi, Richard Lemmers, Pilar Camano, Emiliano Giardina, Nienke van der Stoep, Sarah Burton-Jones, Frederique Magdinier, Valerie Race, Sheila Hawkins, Alexandre Mejat, Piraye Oflazer, Lorenzo Guizzaro, Jamshid Arjomand, Yann Pereon, Giulia Ricci, Enrico Bugiardini, and Alexandra Belayew
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All institutes and research themes of the Radboud University Medical Center ,Neurology ,Pediatrics, Perinatology and Child Health ,Neurology (clinical) ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Genetics (clinical) - Abstract
Item does not contain fulltext
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- 2023
3. New developments in myotonic dystrophies from a multisystemic perspective
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Federica Montagnese and Benedikt Schoser
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musculoskeletal diseases ,medicine.medical_specialty ,Gastrointestinal Diseases ,business.industry ,Perspective (graphical) ,MEDLINE ,Cognition ,Comorbidity ,Disease ,Disease monitoring ,Neurology ,Multidisciplinary approach ,medicine ,Humans ,Myotonic Dystrophy ,Neurology (clinical) ,Intensive care medicine ,business ,Disease burden - Abstract
Purpose of review The multisystemic involvement of myotonic dystrophies (DMs) intricates disease monitoring, patients' care and trial design. This update of the multifaceted comorbidities observed in DMs aims to assist neurologists in the complex management of patients and to encourage further studies for still under-investigated aspects of the disease. Recent findings We reviewed the most recent studies covering pathogenesis and clinical aspects of extra-muscular involvement in DM1 and DM2. The largest body of evidence regards the cardiac and respiratory features, for which experts' recommendations have been produced. Gastrointestinal symptoms emerge as one of the most prevalent complaints in DMs. The alteration of insulin signaling pathways, involved in gastrointestinal manifestations, carcinogenesis, muscle function, cognitive and endocrinological aspects, gain further relevance in the light of recent evidence of metformin efficacy in DM1. Still, too few studies are performed on large DM2 cohorts, so that current recommendations mainly rely on data gathered in DM1 that cannot be fully translated to DM2. Summary Extra-muscular manifestations greatly contribute to the overall disease burden. A multidisciplinary approach is the key for the management of patients. Consensus-based recommendations for DM1 and DM2 allow high standards of care but further evidence are needed to implement these recommendations.
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- 2021
4. The impact of interrupting enzyme replacement therapy in late-onset Pompe disease
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Federica Montagnese, Kristina Gutschmidt, Benedikt Schoser, Corinna Wirner, Stephan Wenninger, and Krisztina Einvag
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0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Weakness ,Neurology ,Late onset ,Interruption of enzyme replacement therapy ,Pulmonary function testing ,03 medical and health sciences ,0302 clinical medicine ,Germany ,Internal medicine ,medicine ,Humans ,Enzyme Replacement Therapy ,Prospective Studies ,Adverse effect ,Prospective cohort study ,Pandemics ,Original Communication ,Clinical outcome ,Glycogen Storage Disease Type II ,SARS-CoV-2 ,business.industry ,nutritional and metabolic diseases ,Pompe disease ,COVID-19 ,alpha-Glucosidases ,Enzyme replacement therapy ,Discontinuation ,030104 developmental biology ,Cardiology ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Glycogen storage disease type 2 - Abstract
Background Late-onset Pompe disease (LOPD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, leading to progressive weakness of locomotor and respiratory muscles. Enzyme replacement therapy (ERT), administered every second week, has been proven to slow down disease progression and stabilize pulmonary function. Due to the COVID-19 pandemic in Germany, ERT was interrupted at our centre for 29 days. As reports on ERT discontinuation in LOPD are rare, our study aimed to analyse the impact of ERT interruption on the change in clinical outcome. Methods We performed a prospective cohort study in 12 LOPD patients. Clinical assessments were performed after ERT interruption and after the next three consecutive infusions. We assessed motor function by muscle strength testing, a 6-minute-walk-test, pulmonary function tests, and adverse events. For statistical analysis, an estimated baseline was calculated based on the individual yearly decline. Results The mean time of ERT interruption was 49.42 days (SD ± 12.54). During ERT interruption, seven patients reported 14 adverse events and two of them were severe. Frequent symptoms were reduced muscle endurance/increased muscle fatigability and shortness of breath/worsening of breathing impairment. After ERT interruption, significant deterioration was found for MIP%pred (p = 0.026) and MRC%pred, as well as a trend to clinical deterioration in FVC%pred and the 6MWT%pred. Conclusion Interruption of ERT was associated with a deterioration in the core clinical outcome measures. Therefore, an interruption of ERT should be kept as short as possible.
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- 2021
5. Location matters – Genotype-phenotype correlation in LRSAM1 mutations associated with rare Charcot-Marie-Tooth neuropathy CMT2P
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Benjamin Hotter, Katherina Eger, Beate Schlotter, Kerstin Becker, Peter Reilich, Isabel Diebold, Ulrike Schön, Hannes Erdmann, Federica Montagnese, Mario Schäff-Vogelsang, Friedrich Stock, Berit Jordan, and Angela Abicht
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Ubiquitin-Protein Ligases ,Nonsense-mediated decay ,Genomics ,Disease ,Biology ,Young Adult ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Charcot-Marie-Tooth Disease ,medicine ,Humans ,Inheritance Patterns ,Gene ,Genetic Association Studies ,Genetics (clinical) ,Aged ,Genetics ,Inheritance (genetic algorithm) ,Middle Aged ,Axons ,Pedigree ,Phenotype ,030104 developmental biology ,Neurology ,Mutation ,Pediatrics, Perinatology and Child Health ,Medical genetics ,Female ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
More than 80 genes are known to be associated with Charcot-Marie-Tooth disease (CMT). Mutations of LRSAM1 were identified as a rare cause and define the subgroup of axonal neuropathy CMT2P. We identified additional 14 patients out of 12 families. Clinical and electrophysiological data confirm a late-onset axonal neuropathy with a predominance of sensorimotor impairment. The patients harbored ten different variants in LRSAM1, seven of which were novel. Due to variable inheritance patterns and clustering of pathogenic variants in 3´-prime exons, interpretation of genetic variants in LRSAM1 is challenging. The majority follows dominant inheritance, whereas recessive inheritance has been described for one variant. Variants at the 3`end may or may not escape from nonsense-mediated decay, thereby defining the pattern of inheritance. Our data emphasize the importance of the C-terminal RING domain, which exerts a dominant-negative effect on protein function, whenever affected by an altered or truncated protein. In conclusion, CMT2P is a rare, but nevertheless relevant cause of adult-onset axonal and painful neuropathy. ACMG (American College of Medical Genetics and genomics) criteria should be carefully applied in variant interpretation, with special attention to premature termination codon-introducing variants and their location within the gene.
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- 2021
6. Non-dystrophic myotonias: clinical and mutation spectrum of 70 German patients
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Benedikt Schoser, Dieter Gläser, Federica Montagnese, and Noemi Vereb
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Adult ,Male ,0301 basic medicine ,myalgia ,medicine.medical_specialty ,Neurology ,Myotonia Congenita ,Myotonia ,03 medical and health sciences ,0302 clinical medicine ,Chloride Channels ,Mexiletine ,Internal medicine ,Humans ,Medicine ,NAV1.4 Voltage-Gated Sodium Channel ,Family history ,Non-dystrophic myotonia ,Retrospective Studies ,CLCN1 ,Original Communication ,biology ,business.industry ,Myotonia congenita ,Genetic heterogeneity ,medicine.disease ,030104 developmental biology ,Mutation ,biology.protein ,Channelopathies ,Female ,Neurology (clinical) ,medicine.symptom ,business ,SCN4A ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Introduction Non-dystrophic myotonias (NDM) are heterogeneous diseases caused by mutations in CLCN1 and SCN4A. The study aimed to describe the clinical and genetic spectrum of NDM in a large German cohort. Methods We retrospectively identified all patients with genetically confirmed NDM diagnosed in our center. The following data were analyzed: demographics, family history, muscular features, cardiac involvement, CK, EMG, genotype, other tested genes, treatment perceived efficacy. Results 70 patients (age 40.2 years ± 14.9; 52.8% males) were included in our study (48 NDM-CLCN1, 22 NDM-SCN4A). The most frequent presenting symptoms were myotonia (NDM-CLCN1 83.3%, NDM-SCN4A 72.2%) and myalgia (NDM-CLCN1 57.4%, NDM-SCN4A 52.6%). Besides a more prominent facial involvement in NDM-SCN4A and cold-sensitivity in NDM-CLCN1, no other significant differences were observed between groups. Cardiac arrhythmia or conduction defects were documented in sixNDM-CLCN1 patients (three of them requiring a pacemaker) and one patient with NDM-SCN4A. CK was normal in 40% of patients. Myotonic runs in EMG were detected in 89.1% of CLCN1 and 78.9% of SCN4A. 50% of NDM-CLCN1 patients had the classic c.2680C>T (p.Arg894*) mutation. 12 new genetic variants are reported. About 50% of patients were not taking any anti-myotonic drug at the last follow-up. The anti-myotonic drugs with the best patient’s perceived efficacy were mexiletine and lamotrigine. Conclusion This study highlights the relevant clinical overlap between NDM-CLCN1 and NDM-SCN4A patients and warrants the use of early and broad genetic investigation for the precise identification of the NDM subtype. Besides the clinical and genetic heterogeneity, the limited response to current anti-myotonic drugs constitutes a continuing challenge.
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- 2020
7. How to capture activities of daily living in myotonic dystrophy type 2?
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Kristina Stahl, Federica Montagnese, Emanuele Rastelli, Benedikt Schoser, and Roberto Massa
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Adult ,Male ,musculoskeletal diseases ,0301 basic medicine ,myalgia ,medicine.medical_specialty ,Activities of daily living ,Psychometrics ,Settore MED/26 ,Severity of Illness Index ,Myotonic dystrophy ,Manual Muscle Testing ,03 medical and health sciences ,0302 clinical medicine ,Activities of Daily Living ,Criterion validity ,medicine ,Humans ,Myotonic Dystrophy ,Patient Reported Outcome Measures ,Registries ,Patient reported outcomes ,Genetics (clinical) ,R-PAct ,business.industry ,Myotonic dystrophy type 2 ,Discriminant validity ,Beck Depression Inventory ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Myotonia ,humanities ,030104 developmental biology ,Neurology ,DM1-Activ-c ,Pediatrics, Perinatology and Child Health ,Physical therapy ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,PROMM - Abstract
Myotonic dystrophy type 2 (DM2) lacks validated patients´ reported outcomes (PROs). This represents a limit for monitoring disease progression and perceived efficacy of symptomatic treatments. Our aim was to investigate whether PROs for activities of daily living designed for other neuromuscular diseases could be used in DM2. Sixty-six DM2 patients completed the following PROs: DM1-Activ-c, Rasch-built Pompe-specific activity (R-PAct) scale, McGill-pain questionnaire, fatigue and daytime sleepiness scale and Beck depression inventory (BDI-II). Clinical data and motor outcome measures (6-minutes walking test - 6MWT, manual muscle testing, quick motor function test and myotonia behavior scale) were collected as well. Patients underwent one visit at baseline and one after 10 months. Ceiling/flooring effects, criterion validity and discriminant validity were calculated. DM1-activ-c and R-PAct showed acceptable ceiling effects despite being built for myotonic dystrophy type 1 and Pompe disease, respectively. The difficulty hierarchy of the single items was better preserved in R-PAct than in DM1-Activ-c. Both tests showed excellent criterion validity highly correlating with 6MWT, quick motor function test, myalgia and disease duration. They could partially discriminate patients with different disability grades. These results suggest that DM1-Activ-c, slightly better than R-PAct, might be adopted for monitoring activities of daily living also in DM2, at least until disease-specific PROs will be available.
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- 2020
8. Dyslexia and cognitive impairment in adult patients with myotonic dystrophy type 1: a clinical prospective analysis
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Federica Montagnese, Kristina Gutschmidt, Stephan Wenninger, and Benedikt Schoser
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0301 basic medicine ,Adult ,medicine.medical_specialty ,Neurology ,Adolescent ,media_common.quotation_subject ,Audiology ,Neurodegenerative ,Dyslexia ,03 medical and health sciences ,0302 clinical medicine ,Reading (process) ,Germany ,medicine ,Humans ,Myotonic Dystrophy ,Cognitive Dysfunction ,Prospective Studies ,Prospective cohort study ,Child ,Neuroradiology ,media_common ,Original Communication ,business.industry ,Cognition ,medicine.disease ,Spelling ,030104 developmental biology ,Cognitive impairment ,IQ ,Cohort ,Neurology (clinical) ,Reading disorder ,business ,030217 neurology & neurosurgery - Abstract
Background Cognitive impairments in patients with myotonic dystrophy type 1 (DM1) have often been described, however, there are only few studies differentiating between partial performance disorders and mental retardation in common. This study focused on the evaluation of reading performance and the frequency of dyslexia in adult DM1 patients. Methods We performed a prospective cohort study including genetically confirmed adult DM1 patients registered in the DM registry of Germany or the internal database of the Friedrich-Baur-Institute, Munich, Germany. For the assessment of the patients’ reading and spelling performance, we used the standardized and validated test ‚Salzburger Lese- und Rechtschreibtest‘ (SLRT II). The ‚CFT-20 R Grundintelligenztest Skala 2‘ in revised ("R") version (CFT 20-R), determining the intelligence level, was appropriate to differentiate between dyslexia and general mental retardation. The diagnosis of dyslexia, the combined reading and spelling disorder, was based on the guidelines for diagnosis and therapy of children and adolescents with dyslexia 2015 (S3-guideline) providing (1) the criterion of the divergence from age level and (2) the criterion of IQ-divergence. Results Fifty-seven DM1 patients participated in our study. Evaluating the reading performance, 16 patients fulfilled the divergence criteria of the age level and 2 patients the IQ-divergence criteria. In total, the diagnosis of a reading disorder was given in 18 DM1 patients (31.6 %). In 11 out of these 18 patients with a reading disorder, a relevant impairment of spelling performance was observed with at least three spelling errors. As there are no normative values for adults in spelling performance, we assume a combined reading disorder and dyslexia, in those 11 DM1 patients (19.3 %). Regarding the separate analyses of the test procedures, in the SLRT II the performance was below average in 40.4 % of all patients for ‘word reading’ and in 61.4 % of all patients for ‘pseudoword reading’. There was a significant positive correlation between the CTG expansion size and a reading disorder (p=0.027). The average IQ of 17 examined DM1 patients was in the lower normal range (86.1 ± 19.1). 54.5 % of patients with reading disorder had a normal IQ. Conclusion The calculated prevalence of dyslexia in the DM1 study cohort was 19.3 % and thus considerably increased compared to the normal German population. As dyslexia is not equivalent to a general cognitive impairment, it is important not to miss dyslexic features in cognitive inconspicuous DM1 patients. Case-by-case one should consider a differential diagnostic approach, as individualized therapies can be offered to support dyslexic patients in their performance.
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- 2020
9. Utility and Results from a Patient-Reported Online Survey in Myotonic Dystrophies Types 1 and 2
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Federica Montagnese, Kristina Stahl, Stephan Wenninger, and Benedikt Schoser
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musculoskeletal diseases ,Pediatrics ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Muscle weakness ,Disease ,medicine.disease ,Myotonia ,Myotonic dystrophy ,Neurology ,medicine ,Neurology (clinical) ,medicine.symptom ,Family history ,Age of onset ,business ,Rare disease - Abstract
Introduction: Myotonic dystrophies (DMs) are the most frequent autosomal dominant neuromuscular disorders in adults. Our objective was to evaluate the utility of an online survey in a rare disease as well as to assess and compare the onset and the progression of clinical symptoms in patients with myotonic dystrophy types 1 (DM1) and 2 (DM2). Methods: We conducted a patient’s reported online survey assessing demographics, disease-related symptoms (age of onset, first symptom, time of diagnosis, current symptoms, inheritance, and family history) combined with capturing current symptoms by validated questionnaires. The questionnaire consisted of open, closed, single- and multiple-choice questions. Multiple answers were possible in some cases. Patients with genetically confirmed DM1 or DM2 who were registered in the German DM registry or the Deutsche Gesellschaft für Muskelkranke e.V. – Diagnostic Group for DMs were invited to participate in this online survey. We calculated descriptive and exploratory analysis, where applicable. Results: Out of 677 data sets from respondents, 394 were suitable for final analysis, containing completed questionnaires from 207 DM1 (56% female) and 187 DM2 patients (71% female). The median age of onset was 28 years for DM1 and 35 years for DM2. Muscular symptoms were most frequently reported as the first symptom. The onset of myotonia was earlier than the onset of muscle weakness in both DM1 and DM2. Forty-four percent of patients with DM1 and one-third of patients with DM2 indicated muscle weakness as the first symptom. Patients with DM1 were significantly younger when experiencing muscle weakness as first symptom. Fatigue was only mentioned by a small fraction of patients as a first symptom but increased significantly in the course of the disease. There was no statistically significant difference in the incidence of cataracts, cardiac symptoms, and gastrointestinal symptoms between DM1 and DM2. Falls were reported almost equally in both groups, and most of the patients reported 2–3 falls within the past year. Discussion: Overall, as our results are consistent with the results of clinical studies and online registries, it can be assumed that this type of systematic gathering of data from patients with rare diseases is useful and provides realistic and appropriate results. Due to the nature of online surveys and the absence of an assessor, some uncertainty remains. Furthermore, survey frauds cannot be completely excluded. An additional clinical assessment could confirm the given information and will improve the utility and validity of reported symptoms participants provide in online surveys. Therefore, we recommend a combination of data collecting by online surveys and clinical assessments.
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- 2020
10. Current Treatment Options for Patients with Myotonic Dystrophy Type 2
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Federica Montagnese
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medicine.medical_specialty ,Neurology ,business.industry ,Myotonic dystrophy type 2 ,Early detection ,Treatment options ,medicine.disease ,Multidisciplinary team ,Myotonic dystrophy ,Intervention (counseling) ,Medicine ,Neurology (clinical) ,business ,Intensive care medicine - Abstract
Purpose of the review Myotonic dystrophy types 1 and 2 are frequent forms of muscular dystrophies in adulthood. Their clinical differences need to be taken into account for the most appropriate treatment of patients. The aim of this article is to provide an overview on the current and upcoming therapeutic options for patients with myotonic dystrophy type 2 (DM2). Recent findings At the moment, no disease-modifying therapies are available for DM2; next-generation therapies may however be available in the near future. In the meanwhile, the symptomatic management of patients has greatly improved, thank to the production of consensus-based standards of care and the growing evidence of efficacy of anti-myotonic drugs, promising employment of cannabinoids for symptom’s relief, regular monitoring, and early detection of treatable extra-muscular manifestations. Summary The treatment of DM2 is currently symptomatic and relies on the coordinated intervention of a multidisciplinary team. It remains to be determined whether upcoming causal therapies for myotonic dystrophy type 1 will be applicable also in DM2.
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- 2021
11. A role for cannabinoids in the treatment of myotonia? Report of compassionate use in a small cohort of patients
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Benedikt Schoser, Kristina Stahl, Stephan Wenninger, and Federica Montagnese
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Adult ,Compassionate Use Trials ,Male ,musculoskeletal diseases ,myalgia ,Abdominal pain ,medicine.medical_specialty ,Constipation ,Side effect ,Myotonic dystrophy ,Muscular Dystrophies ,Myotonia ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cannabinoid Receptor Modulators ,medicine ,Cannabidiol ,Humans ,Dronabinol ,030212 general & internal medicine ,Aged ,biology ,business.industry ,Myalgia ,Middle Aged ,medicine.disease ,biology.organism_classification ,nervous system diseases ,body regions ,Drug Combinations ,Treatment Outcome ,Neurology ,Chronic Disease ,Cohort ,Female ,Neurology (clinical) ,Cannabis ,medicine.symptom ,business ,Oils ,030217 neurology & neurosurgery - Abstract
The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory. Some patients anecdotally report symptoms’ relief through consumption of cannabis. A combination of cannabidiol and tetrahydrocannabinol (CBD/THC) was prescribed as compassionate use to six patients (four patients with myotonic dystrophy types 1 and 2, and 2 patients with CLCN1-myotonia) with therapy-resistant myotonia and myalgia. CBD/THC oil was administered on a low dose in the first 2 weeks and adjusted to a higher dose in the following 2 weeks. Myotonia behaviour scale (MBS), hand-opening time, visual analogue scales (VAS) for myalgia and myotonia, and fatigue and daytime sleepiness severity scale (FSS, ESS) were performed weekly to monitor treatment response. All patients reported an improvement of myotonia especially in weeks 3 and 4 of treatment: MBS improved of at least 2 points in all patients, the hand-opening time variously improved in 5 out of 6 patients. Chronic myalgia was reported by both DM2 patients at baseline, one of them experienced a significant improvement of myalgia under treatment. Some gastrointestinal complaints, as abdominal pain and diarrhoea, improved in 3 patients; however, 4 out of 6 patients reported new-onset constipation. No other relevant side effect was noticed. These first empirical results suggest a potentially beneficial role of CBD/THC in alleviating myotonia and should encourage further research in this field including a randomized-controlled trial on larger cohorts.
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- 2019
12. Editorial: Myotonic Dystrophies: Developments in Research From Bench to Bedside
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Gabriella Silvestri and Federica Montagnese
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outcome measures in DM ,medicine.medical_specialty ,business.industry ,Bench to bedside ,myotonic dystrophy type1 ,lcsh:RC346-429 ,myotonic dystrophy type2 ,cardiac involvement in DM ,Settore MED/26 - NEUROLOGIA ,Neurology ,Steinert's disease ,Medicine ,Neurology (clinical) ,business ,Intensive care medicine ,myotonic dystrophies ,lcsh:Neurology. Diseases of the nervous system - Published
- 2020
13. Editorial: Myotonic Dystrophies: Developments in Research From Bench to Bedside
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Gabriella, Silvestri and Federica, Montagnese
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cardiac involvement in DM ,outcome measures in DM ,CNS involvement in DM ,Editorial ,Neurology ,Steinert's disease ,myotonic dystrophies ,myotonic dystrophy type1 ,tumor risk in DM ,myotonic dystrophy type2 - Published
- 2020
14. Dystrophische und nicht-dystrophische Myotonien
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Federica Montagnese and Benedikt Schoser
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musculoskeletal diseases ,0301 basic medicine ,myalgia ,business.industry ,Sodium channel ,Muscle weakness ,medicine.disease ,Myotonia ,Bioinformatics ,Myotonic dystrophy ,Muscle hypertrophy ,03 medical and health sciences ,Psychiatry and Mental health ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Diabetes mellitus ,Medicine ,Neurology (clinical) ,medicine.symptom ,Differential diagnosis ,business ,030217 neurology & neurosurgery - Abstract
Myotonic syndromes are rare neuromuscular diseases characterized by the clinical or neurophysiological detection of myotonia. The genetic defects involve primarily or secondarily the muscular isoforms of the ion channels. The channel dysfunction consecutively leads to a hyper-excitability of the muscle membrane and the clinical symptom myotonia. Two forms of dystrophic myotonic diseases are currently known: the myotonic dystrophy type 1 (DM1) and the myotonic dystrophy type 2 (DM2). They are multisystemic diseases clinically characterized by a combination of myotonia and other muscular symptoms (muscle weakness, wasting and myalgia) together with the involvement of other organs and systems (cataract, diabetes, heart diseases, hormone dysfunctions). The non-dystrophic myotonic diseases are caused by mutations affecting either the chloride ion channels or the sodium ion channels. The clinical picture is dominated by the presence of myotonia and other minor muscular complaints as mild episodic weakness and muscle hypertrophy. The differential diagnosis among the myotonic syndromes is extremely challenging leading to a significant diagnostic delay. This review will update on the main clinical, diagnostic and therapeutic aspects of myotonic syndromes to guide general neurologists through an earlier diagnosis and better management.
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- 2018
15. Evaluating the diagnostic utility of new line immunoassays for myositis antibodies in clinical practice: a retrospective study
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Haris Babačić, Benedikt Schoser, Federica Montagnese, and Peter Eichhorn
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Adult ,Male ,medicine.medical_specialty ,Neurology ,Gastroenterology ,Sensitivity and Specificity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Myopathy ,Myositis ,Neuroradiology ,Aged ,Autoantibodies ,Retrospective Studies ,Immunoassay ,Muscle biopsy ,biology ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,biology.protein ,Female ,Neurology (clinical) ,Antibody ,Differential diagnosis ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Myositis-associated antibodies (MAA) and myositis-specific antibodies (MSA) are detected in patients with idiopathic inflammatory myopathies (IIM); their role as diagnostic biomarkers is however still debated. The aim of our study was to assess the utility of MAA/MSA assessed by new line immunoassays in detecting myositis among neuromuscular patients. We retrospectively analysed sera samples obtained from patients tested for myositis antibodies with the “Euroline: Autoimmune Inflammatory Myopathies 16Ag” and “myositis profile 3” kits (Mi-2, TIF1γ, MDA5, NXP2, SAE1, Jo-1, SRP, PL-7/12, EJ, OJ, Ro-52, Ku, PM-Scl75/100). First symptom, CK, EMG, muscle biopsy and diagnosis were also analysed. Using logistic regression analysis, two diagnostic models were built to evaluate the diagnostic power of MAA/MSA in distinguishing myositis patients from controls and other myopathies. 1229 patients were identified. 141 patients had a bioptic confirmed IIM; other diagnoses included: myopathy (n = 357), other neuromuscular diseases (n = 144) and no neuromuscular diseases (n = 587). The specificity was 95% for MSA and 89% for MAA, the sensitivity 20% and 22%, respectively. MAA showed no use in differentiating myositis patients from controls, whereas MSA had limited effect (OR = 5.165), compared to other variables as EMG (OR = 47.755) or CK > 2000 U/L (OR = 45.307). MSA were, however, the most useful parameter differentiating IIM from non-IIM patients (OR = 7.259), better than CK > 2000 U/L (OR = 4.033) and MAA (OR = 2.737). Line immunoassays for myositis antibodies show high specificity but low sensitivity. Their usefulness as diagnostic biomarkers widely depends on the clinical settings. Our study suggests that MSA/MAA should be used for confirmatory and differential diagnosis rather than for screening purposes in inflammatory myopathies.
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- 2018
16. The risks of using non-specific outcome measures to capture activities of daily living in myotonic dystrophy type 2 - Response
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null On behalf of all authors, Federica Montagnese, and Benedikt Schoser
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medicine.medical_specialty ,Activities of daily living ,business.industry ,Myotonic dystrophy type 2 ,Outcome measures ,Physical medicine and rehabilitation ,Neurology ,Non specific ,Activities of Daily Living ,Outcome Assessment, Health Care ,Pediatrics, Perinatology and Child Health ,Humans ,Myotonic Dystrophy ,Medicine ,Neurology (clinical) ,business ,Genetics (clinical) - Published
- 2021
17. Long-term whole-body vibration training in two late-onset Pompe disease patients
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Federica Montagnese, Stephan Wenninger, Simone Thiele, and Benedikt Schoser
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Adult ,medicine.medical_specialty ,Neurology ,030209 endocrinology & metabolism ,Late onset ,Walking ,Dermatology ,Isometric exercise ,Vibration ,Pulmonary function testing ,Manual Muscle Testing ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Glycogen storage disease type II ,medicine ,Humans ,Whole body vibration ,Enzyme Replacement Therapy ,Longitudinal Studies ,Muscle Strength ,Glycogen Storage Disease Type II ,business.industry ,General Medicine ,Enzyme replacement therapy ,medicine.disease ,Psychiatry and Mental health ,Exercise Test ,Physical therapy ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
The treatment of late-onset Pompe disease (LOPD) relies on enzyme replacement therapy (ERT) and physiotherapy but the most appropriate exercise program is not yet established. Whole-body vibration training (WBVT) has showed promising results, improving motor performances in various populations. Our aim is to assess the effects of WBVT performed by two LOPD patients in addition to ERT and physiotherapy. A side-alternating WBVT lasting 2 years; clinical assessments included: manual muscle testing (MRC sumscore), knee extension and arm flection isometric strength (multi-muscle tester M3diagnos), timed function tests (10 m walking, standing-up from chair, ascending 4-steps), 6 min walking (6 MWT), motor disability (Walton Gardner-Medwin scale), pulmonary function. Follow-up evaluations performed for 9 years since ERT start (pre-WBVT and post-WBVT) are reported for comparison. MRC sumscore improved in both patients (Pt.1:41 → 48, Pt.2:42 → 47) as isometric strength of knee extension (Pt.1: + 62 %, Pt.2: + 26 %) and arm flection (Pt.1: + 88 %, Pt.2: + 66 %), 6 MWT improved in Pt.1 (+75 m). Timed function tests did not greatly change. Patients reported no significant CK elevation or WBVT-related complaints. WBVT may be safely used in LOPD and seems to moderately boost muscle strength in patients receiving ERT and physiotherapy for more than 3 years. Larger cohorts should be studied to better assess WBVT potential as adjunctive exercise tool in LOPD.
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- 2016
18. Ausbildung und berufliche Qualifikation von Erwachsenen mit Myotonen Dystrophien – eine fehlgeleitete Wahrnehmung durch die Facies myopathica?
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A. Schüller, Benedikt Schoser, Kristina Stahl, Stephan Wenninger, and Federica Montagnese
- Subjects
Gynecology ,03 medical and health sciences ,Psychiatry and Mental health ,medicine.medical_specialty ,0302 clinical medicine ,Neurology ,business.industry ,medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,030227 psychiatry - Abstract
Hintergrund: Myotone Dystrophien Typ 1 und 2 (DM1 / DM2) sind die haufigsten progressiven, segmental progeroiden, multisystemischen, erblichen Muskelerkrankungen im Erwachsenenalter. Die Storung der Exekutivfunktionen bei DM1-Patienten stellt einen wesentlichen Krankheitsanteil dar. Durch die pathognomonische Facies myopathica wird u. a. ein niedriges Bildungsniveau bei DM1 suggeriert. Detailliertere Untersuchungen zum Bildungsniveau dieser Patientengruppen existieren aber nicht. Methoden: Wir nutzten einen standardisierten strukturierten Fragebogen zur Untersuchung des Bildungsniveaus bei Patienten mit molekulargenetisch gesicherter DM1 und DM2. Inhalte der Untersuchung umfassten das Bildungsniveau, den hochsten erreichten Schulabschluss und die berufliche Qualifikation. Die erhobenen Daten wurden mit vorliegenden Daten zur Bildung der Normalbevolkerung verglichen. Ergebnisse: Aus einem Gesamtkollektiv von 546 DM Patienten nahmen 125 DM1- und 156 DM2-Patienten (51 %) an dieser Studie teil. Fur den hochsten Schulabschluss bestand ein statistisch signifikanter Unterschied zwischen den Kollektiven und der Normalbevolkerung. 50,4 % der DM1- und 48,3 % der DM2-Patienten erreichten die (Fach-)Hochschulreife, wahrend es in der Normalbevolkerung durchschnittlich 29,6 % sind. Fur die weitere berufliche Qualifizierung fanden sich nur geringe Abweichungen zwischen den Kohorten (Fach-/Hochschulabschluss: DM1: 25 %, DM2 23 %; Ausbildung/Lehre: DM1: 61 %, DM2 71 %) und der Normalbevolkerung. Es zeigte sich eine signifikant erhohte Pravalenz von „Rechtschreibproblemen“ (p = 0,039), „Schwierigkeiten beim Kopfrechnen“ (p = 0,043), und Einstufung der Patienten „mit Lernproblemen“ (p = 0,012) bei DM1-Patienten. Diskussion: Die allgemeine klinische Wahrnehmung der DM1-Patienten ist u. a. durch die Facies myopathica determiniert. Mit der Schwache der Gesichtsmuskulatur und dem offenstehenden Mund wird ein kognitives Defizit assoziiert, das diese Patientengruppe stigmatisiert. Die in unserer Studie dargestellten minimalen Abweichungen zwischen den Patientenkollektiven und der Normalbevolkerung weisen darauf hin, dass das erreichbare Bildungsniveau durch die multisystemische Erkrankung nicht wesentlich eingeschrankt wird. Beurteilung: Die im klinischen Alltag vorhandene Fehleinschatzung der kognitiven Leistungsfahigkeit von Erwachsenen mit Myotonen Dystrophien sollte revidiert werden.
- Published
- 2016
19. Cannabis use in myotonic dystrophy patients in Germany and USA: a pilot survey
- Author
-
Anke Klein, Stephan Wenninger, Federica Montagnese, Kristina Stahl, Molly White, and Benedikt Schoser
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Pilot survey ,MEDLINE ,Pilot Projects ,Medical Marijuana ,Myotonic dystrophy ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Germany ,Medicine ,Humans ,Myotonic Dystrophy ,Young adult ,Psychiatry ,Neuroradiology ,business.industry ,Cannabinoids ,Cannabis use ,Middle Aged ,medicine.disease ,United States ,030104 developmental biology ,Neurology ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Published
- 2018
20. How to Interpret Abnormal Findings of Spirometry and Manometry in Myotonic Dystrophies?
- Author
-
Haris Babačić, Benedikt Schoser, Stephan Wenninger, Vindi Jurinovic, Kristina Stahl, Federica Montagnese, and Olga Goldina
- Subjects
Spirometry ,Adult ,Male ,medicine.medical_specialty ,Vital capacity ,Manometry ,Maximal Respiratory Pressures ,Population ,Reference range ,Pulmonary function testing ,03 medical and health sciences ,FEV1/FVC ratio ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Myotonic Dystrophy ,Respiratory system ,education ,Aged ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Middle Aged ,Cross-Sectional Studies ,030228 respiratory system ,Neurology ,Cardiology ,Female ,Neurology (clinical) ,business ,Respiratory Insufficiency ,030217 neurology & neurosurgery - Abstract
BACKGROUND/AIM Pulmonary function tests are used for screening respiratory insufficiency in patients with myotonic dystrophy (DM). We analysed the agreement between two different approaches in assessment of abnormal findings of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), in DM patients. METHODS We used Cohen's \textgreekk- and Bangdiwala's B- statistic to compare the agreement between different cut-off values recommended by experts (ENMC) and the cut-off values based on the reference range (RR). We further analysed their sensitivity (Sn) and specificity (Sp) in detecting symptoms associated with respiratory insufficiency. RESULTS The observed agreement was: 1) for FVC: \textgreekk= -0.002, B = 0.406; 2) for FEV1: \textgreekk= 0.944, B = 0.946; 3) for MIP: \textgreekk= 0.625, B = 0.674; and 4) for MEP: \textgreekk= 0.241, B = 0.373. Overall, RR cut-off values showed higher sensitivity, whereas the ENMC values showed higher specificity in detecting symptoms of respiratory involvement. CONCLUSIONS The two approaches showed perfect agreement in assessment of FEV1, substantial agreement for MIP, and weak agreement for FVC and MEP. RR is an established method of assessment for spirometry and should be favoured because it takes variability within the population into account. Further development and validation of regression equations for RR calculations of predicted maximal respiratory pressures, with corresponding lower limits of normal, is required.The B statistic is more robust in assessing agreement between two diagnostic methods, resolving the issue of the \textgreekk paradox.
- Published
- 2018
21. Towards clinical outcome measures in myotonic dystrophy type 2: a systematic review
- Author
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Benedikt Schoser, Roberto Massa, Federica Montagnese, and Emanuele Rastelli
- Subjects
musculoskeletal diseases ,0301 basic medicine ,myalgia ,medicine.medical_specialty ,Myotonic dystrophy type 2 ,muscle strength ,myotonic dystrophy type 2 ,outcome assessment ,outcome scale ,physical function ,Humans ,Myotonic Dystrophy ,Reproducibility of Results ,Treatment Outcome ,Settore MED/26 ,Myotonic dystrophy ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,medicine ,In patient ,business.industry ,Outcome measures ,medicine.disease ,Myotonia ,Therapeutic trial ,030104 developmental biology ,Neurology ,Muscle strength ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
PURPOSE OF REVIEW Myotonic dystrophies are the most frequent muscular dystrophies in adulthood; however, myotonic dystrophy type 2 (DM2) is by far less prevalent than myotonic dystrophy type 1 (DM1). Consequently, studies on large cohorts are lacking and disease-specific outcome measures have not been developed (see video abstract, Supplemental Digital Content 1, http://links.lww.com/CONR/A44).The aim of this review is to systematically evaluate the outcome measures applied in patients with DM2 and to identify tests adopted from other neuromuscular disorders potentially suitable for DM2.A systematic review of functional tests and patient reported outcomes (PROs) previously used in DM2 has been performed. In addition, we reviewed functional tests and PROs previously used in neuromuscular diseases (NMDs). Based on this approach, we propose a battery of tests to be validated in DM2. RECENT FINDINGS No outcome measures or PROs have been validated in DM2. The most used PROs in DM2 were INQoL, SF-36, MPQ, and BPI. It is not clear whether it is better to use MMT or QMT to assess muscle strength. The algometer seems to be a useful tool to assess myalgia. No currently adopted tests or PROs seem effective to assess the mild myotonia of DM2. Several outcome measures used in other NMDs (e.g. 6MWT, QMFT, GSGC) might be suitable for DM2; however, their disease-specific validity needs to be explored. SUMMARY Although DM2 has a milder and more heterogeneous phenotype than DM1, there is an urgent need to develop validated outcome measures in DM2. The current lack of validated DM2 tests will delay the start of therapeutic trials.
- Published
- 2018
22. Core Clinical Phenotypes in Myotonic Dystrophies
- Author
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Benedikt Schoser, Federica Montagnese, and Stephan Wenninger
- Subjects
musculoskeletal diseases ,0301 basic medicine ,DM2 ,Respiratory impairment ,Signs and symptoms ,Review ,Bioinformatics ,Myotonic dystrophy ,lcsh:RC346-429 ,repeat expansion diseases ,03 medical and health sciences ,0302 clinical medicine ,medicine ,lcsh:Neurology. Diseases of the nervous system ,business.industry ,phenotypes ,Myotonia ,medicine.disease ,Phenotype ,myotonia ,030104 developmental biology ,Neurology ,sleep disorders ,Neurology (clinical) ,DM1 ,business ,myotonic dystrophies ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Myotonic dystrophy type 1 (DM1) and type 2 (DM2) represent the most frequent multisystemic muscular dystrophies in adulthood. They are progressive, autosomal dominant diseases caused by an abnormal expansion of an unstable nucleotide repeat located in the non-coding region of their respective genes DMPK for DM1 and CNBP in DM2. Clinically, these multisystemic disorders are characterized by a high variability of muscular and extramuscular symptoms, often causing a delay in diagnosis. For both subtypes, many symptoms overlap, but some differences allow their clinical distinction. This article highlights the clinical core features of myotonic dystrophies, thus facilitating their early recognition and diagnosis. Particular attention will be given to signs and symptoms of muscular involvement, to issues related to respiratory impairment, and to the multiorgan involvement. This article is part of a Special Issue entitled “Beyond Borders: Myotonic Dystrophies – A European Perception”.
- Published
- 2018
23. P.29Patient reported outcome measures in myotonic dystrophy type 2
- Author
-
Emanuele Rastelli, Benedikt Schoser, Federica Montagnese, Kristina Stahl, and N. Khizanishvili
- Subjects
Pediatrics ,medicine.medical_specialty ,Neurology ,business.industry ,Pediatrics, Perinatology and Child Health ,medicine ,Outcome measures ,Myotonic dystrophy type 2 ,Neurology (clinical) ,business ,Genetics (clinical) - Published
- 2019
24. Acute parkinsonism as first manifestation of systemic lupus erythematosus unmasked by CMV infection
- Author
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Olimpia Musumeci, Marco Marino, Antonio Toscano, Federica Montagnese, and Francesca Morgante
- Subjects
medicine.medical_specialty ,Lupus erythematosus ,Neurology ,business.industry ,Parkinsonism ,Congenital cytomegalovirus infection ,Dermatology ,General Medicine ,medicine.disease ,Psychiatry and Mental health ,Antiphospholipid antibodies ,Cytomegalovirus ,Encephalitis ,Systemic lupus erythematosus ,Medicine ,Neurology (clinical) ,Neurosurgery ,business ,Anti-SSA/Ro autoantibodies ,Neuroradiology - Published
- 2014
25. 'Orbiting around' the orbital myositis: clinical features, differential diagnosis and therapy
- Author
-
Federica Montagnese, Stephan Wenninger, and Benedikt Schoser
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Neurology ,medicine.medical_treatment ,MEDLINE ,Diagnosis, Differential ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Orbital Myositis ,medicine ,Humans ,Medical diagnosis ,Intensive care medicine ,Neuroradiology ,business.industry ,Middle Aged ,Radiation therapy ,030221 ophthalmology & optometry ,Female ,Neurology (clinical) ,Differential diagnosis ,business ,030217 neurology & neurosurgery ,Rare disease - Abstract
Orbital myositis (OM) is a rare disease whose clinical heterogeneity and different treatment options represent a diagnostic and therapeutic challenge. We aim to review the state of knowledge on OM, also describing a cohort of patients diagnosed in our centre, to highlight some remarkable clinical features. A literature review was conducted in PubMed and Medline databases. The herein described cohort is composed of seven OM patients, diagnosed according to clinical, laboratory and neuroradiological features, whose clinical data were retrospectively analysed. OM is a non-infectious, inflammatory process primarily involving extraocular eye-muscles. It typically presents as an acute to sub-acute, painful ophthalmoplegia with signs of ocular inflammation, but atypical cases without pain or with a chronic progression have been described. The wide range of OM mimicking diseases make a prompt diagnosis challenging but orbit MRI provides valuable clues for differential diagnosis. Timely treatment is greatly important as OM promptly responds to steroids; nevertheless, partial recovery or relapses often occur. In refractory, recurrent or steroid-intolerant cases other therapeutic options (radiotherapy, immunosuppressants, immunoglobulins) can be adopted, but the most effective therapeutic management is yet to be established. In this review, we provide a detailed clinical description of OM, considering the main differential diagnoses and suggesting the most useful investigations. In light of the currently available data on therapy efficacy, we propose a therapeutic algorithm that may guide neurologists in OM patients' management.
- Published
- 2015
26. Breathing Pattern and Central Ventilatory Drive in Late-Onset Pompe Disease
- Author
-
Paolo Ruggeri, Olimpia Musumeci, Giuseppe Girbino, Federica Montagnese, and Antonio Toscano
- Subjects
medicine.medical_specialty ,business.industry ,Central nervous system ,Diaphragmatic breathing ,Late onset ,Trunk ,Pathophysiology ,medicine.anatomical_structure ,Neurology ,Internal medicine ,Cardiology ,Medicine ,Neurology (clinical) ,Brainstem ,Respiratory system ,business ,Phrenic nerve - Abstract
Pompe disease is an autosomal recessive disorder characterized by acid alpha-glucosidase (GAA) defi ciency that results in intralysosomal glycogen accumulation affecting skeletal muscles with more specifi c impairment of proximal limb, trunk, and respiratory muscles. Pulmonary symptoms may represent one of the initial manifestations of late-onset Pompe disease (LOPD) in patients, even those still ambulating, and may include exertional dyspnea, sleep disordered breathing, impaired cough, and chronic respiratory insuffi ciency. LOPD respiratory disturbances have commonly been attributed to muscle defi ciency, mostly diaphragmatic. Since glycogen accumulation has been documented in the peripheral nerves (i.e. the phrenic nerve) and the central nervous system (brainstem and spinal motoneurons), either in patients or in animal models, a potential neural respiratory control dysfunction has also been postulated. The aim of this study was to determine the breathing pattern and central ventilatory drive in patients with LOPD to better understand the pathophysiology of their respiratory impairment.
- Published
- 2015
27. Clinical and molecular aspects of 30 patients with late-onset Pompe disease (LOPD): unusual features and response to treatment
- Author
-
Emanuele Barca, P. De Filippi, Alba Migliorato, Carmelo Rodolico, Olimpia Musumeci, A. Ciranni, Federica Montagnese, Antonio Toscano, Stefania Mondello, and Cesare Danesino
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Pathology ,Neurology ,DNA Mutational Analysis ,Late onset ,Metabolic myopathy ,Severity of Illness Index ,Ureohydrolases ,Leukoencephalopathy ,Cohort Studies ,Young Adult ,medicine ,ERT ,Glycogen storage disease type 2 ,Pompe disease ,Humans ,Respiratory function ,Enzyme Replacement Therapy ,Muscle, Skeletal ,Analysis of Variance ,Genetic heterogeneity ,business.industry ,Glycogen Storage Disease Type II ,Metabolic disorder ,alpha-Glucosidases ,Enzyme replacement therapy ,Middle Aged ,medicine.disease ,Respiration Disorders ,Magnetic Resonance Imaging ,Mutation ,Female ,Neurology (clinical) ,business - Abstract
Pompe disease is a rare metabolic disorder, due to mutations in the gene encoding acid alpha-glucosidase (GAA), of which infantile and late-onset forms may occur. Aim of the work was to analyze clinical and laboratory data of a cohort of late-onset Pompe disease (LOPD) patients, collected during the last 15 years and to point out unusual phenotypic/genotypic features as well as enzyme replacement therapy (ERT) responses. We diagnosed 30 LOPD patients; at follow-up, they underwent motor, respiratory, cardiac and muscle MRI evaluations. Motor performances were tested by Walton Gardner-Medwin, GSGC and 6MWT tests. Respiratory function was assessed as FVC % in upright/supine position. LOPD presentations were represented by presymptomatic hyperCKemia (37 %), proximal/axial muscle weakness (53 %) and respiratory impairment (10 %). Median diagnostic delay was 8.6 years (±8.8). Atypical features were observed in 4 patients: marked distal muscle weakness and severe hearing loss at onset, as well as leukoencephalopathy and mesial temporal sclerosis during the disease course. By GAA sequence analysis, two causing mutations were detected in 22/30 patients, only one in the remaining 8 subjects. Overall, 29/30 patients harbored the common c.−32−13T>G mutation (2 were homozygous). Two new DNA variations were discovered (c.2395C>G, c.1771C>T). 14 patients received ERT for up to 60 months. Our study confirms LOPD clinical and genetic heterogeneity: atypical features may contribute to expand the clinical phenotype highlighting its multi-systemic nature. A timely diagnosis could allow early ERT start. An accurate follow-up is recommended to evaluate treatment responses.
- Published
- 2014
28. Recurrent rhabdomyolysis due to muscle β-enolase deficiency: very rare or underestimated?
- Author
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Richard Godfrey, A. Ciranni, R. Kirk, Stefen Brady, S. Romeo, Shamima Rahman, Olimpia Musumeci, Carmelo Rodolico, Ros Quinlivan, E Murphy, Elizabeth Allen, Federica Montagnese, Antonio Toscano, and M'hammed Aguennouz
- Subjects
myalgia ,Muscle tissue ,Adult ,Male ,medicine.medical_specialty ,Glycogenosis ,Mutation, Missense ,Exercise intolerance ,Metabolic myopathy ,Compound heterozygosity ,Rhabdomyolysis ,ENO3 ,Internal medicine ,Muscle β-enolase ,Medicine ,Humans ,Muscle, Skeletal ,Muscle Cramp ,Muscle biopsy ,medicine.diagnostic_test ,business.industry ,Homozygote ,Myalgia ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,Neurology ,Phosphopyruvate Hydratase ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Muscle β-enolase deficiency is a very rare inherited metabolic myopathy caused by an enzymatic defect of distal glycolysis. So far, the condition has been described in only one patient with mutations in ENO3 in a compound heterozygous state who presented with exercise intolerance, post-exercise myalgia and mild hyperCKemia but no pigmenturia. We describe two men, one Italian and one Turkish, with consanguineous parents, who complained of several episodes of intense myalgia, cramps, generalized muscle tenderness and dark urine. No other family members reported similar symptoms. In both cases, there was a very mild rise in lactate during a forearm exercise test. Muscle biopsy showed minimal changes with no lipid or glycogen accumulation. Biochemical studies on muscle tissue demonstrated a marked reduction of muscle β-enolase activity (20 and 10 % of residual activity, respectively). Molecular genetic analysis of ENO3 gene revealed two novel homozygous missense mutations, (p.Asn151Ser and p.Glu187Lys). Both mutations segregated as expected in the two families. Although quite rare, muscle β-enolase deficiency should be considered in the differential diagnosis of patients presenting with recurrent rhabdomyolysis. It may present also with a more severe phenotype than previously thought.
- Published
- 2014
29. T.P.34
- Author
-
Umberto Aguglia, E. Ferlazzo, Olimpia Musumeci, Carmelo Rodolico, Federica Montagnese, S. Romeo, and Antonio Toscano
- Subjects
Proband ,medicine.medical_specialty ,Microcephaly ,Pediatrics ,Muscle biopsy ,Movement disorders ,medicine.diagnostic_test ,business.industry ,Encephalopathy ,Neurological examination ,medicine.disease ,Epilepsy ,Endocrinology ,Neurology ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Neurology (clinical) ,medicine.symptom ,business ,Rhabdomyolysis ,Genetics (clinical) - Abstract
We report a 44-years-old man, who presented, since the age of 20, recurrent episodes of rhabdomyolysis after exercise or prolonged fasting; he also showed a mild mental retardation and sporadic choreo-athetoid movements. His 14-years-old son had a psychomotor developmental delay with episodes of drowsiness and head drops, occurring mainly at fasting, and exercise-induced choreo-athetoid movements but no history of pigmenturia. Neurological examination revealed microcephaly, mild spastic ataxia and mental retardation. EEG was normal in the proband but in the son showed, during fasting, diffuse spike-wave discharges disappearing after food intake. Brain MRI was normal in both. CSF analysis in the son revealed hypoglycorrhachia (40 mg/dl). Clinical and laboratory findings suggested a search for mutations in SCL2A1 (GLUT-1) gene that revealed in both subjects, an already reported pathogenic heterozygous mutation (R333W). GLUT-1 Deficiency Syndrome (DS) is a rare encephalopathy, caused by impaired glucose transport into the brain, presenting with early-onset epilepsy, movement disorders, developmental delay and microcephaly but rhabdomyolysis has never been reported in similar cases. To better define the origin of recurrent exercise-induced rhabdomyolysis in the father, he underwent forearm ischemic test (normal), EMG (myopathic pattern) and muscle biopsy that evidenced unspecific changes. Muscle biochemical studies excluded the most common metabolic causes of recurrent rhabdomyolysis, but VLCAD gene analysis in the father showed two known heterozygous mutations (p.G185S and p.R385W) whereas his son carried only the p.G185S. Nowadays, it is evident that cases of “double trouble” are increasing and, when a known phenotype is accompanied by some atypical features, we should think of an alternative explanation of unusual presentations.
- Published
- 2014
30. Blood film examination for vacuolated and PAS-positive lymphocytes as diagnostic screening test for patients with late onset Pompe disease (LOPD)
- Author
-
Marco Marino, Daniela Parisi, Alba Migliorato, Olimpia Musumeci, Federica Montagnese, A. Toscano, A. Ciranni, and Carmelo Rodolico
- Subjects
myalgia ,Pathology ,medicine.medical_specialty ,Muscle biopsy ,Proximal muscle weakness ,medicine.diagnostic_test ,Glycogen ,business.industry ,Late onset ,Giemsa stain ,chemistry.chemical_compound ,Neurology ,chemistry ,Pediatrics, Perinatology and Child Health ,Cohort ,Medicine ,Neurology (clinical) ,medicine.symptom ,business ,Diagnosis of Pompe disease ,vacuoles ,PAS-positive lymphocytes ,Genetics (clinical) ,Cytoplasmic Vacuolation - Abstract
Pompe disease is an inherited metabolic multisystemic disorder resulting in glycogen storage in different tissues, caused by a deficiency of the lysosomal enzyme acid alfa-glucosidase. Glycogen storage is often a morphological marker in muscle biopsy of Pompe patients but it could be also present in other tissues. Abnormal cytoplasmic vacuolation of lymphocytes, detectable on routine blood film examination, has been recently proposed as possible screening in these patients. We examined blood smear of 16 LOPD patients, aged 14-71 years. The cohort phenotype encompasses 3 patients with presymptomatic hyperckemia, 2 with myalgia and faticability, and 11 with proximal muscle weakness. Among those, 6 patients are on ERT treatment. We collected also peripheral blood films from 20 healthy controls and from 12 patients affected by other muscle glycogenoses. Blood sample was followed by preparation of four blood films: two of them were stained by May-Grunwald/ Giemsa (MGG) end the other two by PAS. . To investigate the diagnostic value of the test, we quantified the percentage of vacuolated lymphocytes and the percentage of PAS-positive lymphocytes. The mean values of PAS-positive lymphocytes in LOPD patients (25.6%) were significantly higher than those of healthy controls (4.6%) and of patients with other muscle glycogenoses (4.8%). In this group of patients, we have shown that PAS-positive cytoplasmic vacuolation of lymphocytes in peripheral blood films could be considered as a reliable screening tool to support an early diagnosis of Pompe disease., Italian Journal of Anatomy and Embryology, Vol. 120, No. 1 (Supplement) 2015
- Published
- 2015
31. Intracranial arterial abnormalities in patients with late onset Pompe disease
- Author
-
A. Ciranni, A. Toscano, Stefania Mondello, Marcello Longo, Maria Cucinotta, Federica Montagnese, Francesca Granata, Olimpia Musumeci, and Carmelo Rodolico
- Subjects
medicine.medical_specialty ,Neurology ,business.industry ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Cardiology ,Late onset ,In patient ,Neurology (clinical) ,Disease ,business ,Genetics (clinical) - Published
- 2015
32. 8 Years of Experience with Alglucosidase Alpha Treatment: Facts and Perspectives
- Author
-
Federica Montagnese, Olimpia Musumeci, Antonio Toscano, and Stefania Mondello
- Subjects
Oncology ,medicine.medical_specialty ,Neurology ,business.industry ,Internal medicine ,medicine ,Alpha (ethology) ,Neurology (clinical) ,business - Published
- 2015
33. Intracranial Arterial Abnormalities in Patients with Late-Onset Pompe Disease
- Author
-
Francesca Granata, Federica Montagnese, Olimpia Musumeci, A. Ciranni, Marcello Longo, Carmelo Rodolico, and Antonio Toscano
- Subjects
Pediatrics ,medicine.medical_specialty ,Text mining ,Neurology ,business.industry ,MEDLINE ,medicine ,In patient ,Late onset ,Neurology (clinical) ,Disease ,business - Published
- 2015
34. T.P.16
- Author
-
Emanuele Barca, S. Romeo, Mohammed Aguennouz, Antonio Toscano, Olimpia Musumeci, A. Ciranni, Federica Montagnese, and Carmelo Rodolico
- Subjects
medicine.medical_specialty ,Pathology ,business.industry ,Genetic heterogeneity ,Enzyme replacement therapy ,Metabolic myopathy ,medicine.disease ,Asymptomatic ,Gastroenterology ,Leukoencephalopathy ,FEV1/FVC ratio ,Neurology ,Respiratory failure ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Respiratory function ,Neurology (clinical) ,medicine.symptom ,business ,Genetics (clinical) - Abstract
Pompe disease is a rare metabolic myopathy due to mutations in the gene encoding acid alpha-glucosidase (GAA) involved in glycogen degradation. Two clinical presentations can occur: infantile form and late-onset form. Herein, we describe a cohort of 33 late-onset Pompe disease (LOPD) patients diagnosed at our centre from 1997 to date. Our aim is to present clinical and functional data collected in this long time lapse and to describe unusual clinical and genetic features. LOPD diagnosis was made with muscle GAA residual activity assay and GAA sequence analysis. At follow-up patients underwent motor, respiratory, cardiac and muscle MRI evaluations. Motor performances were tested with Walton Gardner-Medwin, MRC, GSGC, 6MWT. Respiratory function was assessed through FVC% in upright and supine position 19 males, 14 females. The onset symptom was asymptomatic hyperckemia in 13 patients (39%), proximal weakness in 19 (57%) and respiratory failure in 1 (3%). Atypical clinical features were observed in 4 patients: a 66year-old female with a severe distal muscle weakness; a 70-year-old male with mesial temporal sclerosis; a 46-years-old male with severe hearing loss and a 52-year-old male with leukoencephalopathy. The median age at diagnosis was 38years, median diagnostic delay 8.3years. GAA sequence analysis showed the common IVS1–13T>G mutation in all patients associated, in 25 patients, with a second mutation. Two brothers were IVS1–13T>G homozygous and 1 patient had a new mutation (c.2395C>G). In the remaining 8 no second mutation was found. 17 patients started enzyme replacement therapy (ERT). Our study confirms LOPD clinical and genetic heterogeneity. The atypical features encountered may contribute to expand the clinical aspects of the disease highlighting its multisystemic nature. Early diagnosis allows, when indicated, earlier ERT initiation even if, in our cohort, treatment responses were variable and not clearly correlated with diagnostic delay.
- Published
- 2014
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