Journal of Neuromuscular Diseases - Volume 7, issue 4

Authors: Reimann, Jens | Kornblum, Cornelia

Article Type: Review Article

Abstract: There is increasing evidence of central nervous system involvement in numerous neuromuscular disorders primarily considered diseases of skeletal muscle. Our knowledge on cerebral affection in myopathies is expanding continuously due to a better understanding of the genetic background and underlying pathophysiological mechanisms. Intriguingly, there is a remarkable overlap of brain pathology in muscular diseases with pathomechanisms involved in neurodegenerative or neurodevelopmental disorders. A rapid progress in advanced neuroimaging techniques results in further detailed insight into structural and functional cerebral abnormalities. The spectrum of clinical manifestations is broad and includes movement disorders, neurovascular complications, paroxysmal neurological symptoms like migraine and epileptic …seizures, but also behavioural abnormalities and cognitive dysfunction. Cerebral involvement implies a high socio-economic and personal burden in adult patients sometimes exceeding the everyday challenges associated with muscle weakness. It is especially important to clarify the nature and natural history of brain affection against the background of upcoming specific treatment regimen in hereditary myopathies that should address the brain as a secondary target. This review aims to highlight the character and extent of central nervous system involvement in patients with hereditary myopathies manifesting in adulthood, however also includes some childhood-onset diseases with brain abnormalities that transfer into adult neurological care. Show more

Keywords: Myopathy, brain, central nervous system, neuromuscular disorder, MRI, intellectual disability, behavioural abnormalities

DOI: 10.3233/JND-200507

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 367-393, 2020

Authors: Sato, Takahiko

Article Type: Review Article

Abstract: Induced pluripotent stem cells (iPSCs) have the potential to differentiate into various types of cells and tissues including skeletal muscle. The approach to convert these stem cells into skeletal muscle cells offers hope for patients afflicted with skeletal muscle diseases such as Duchenne muscular dystrophy (DMD). Several methods have been reported to induce myogenic differentiation with iPSCs derived from myogenic patients. An important point for generating skeletal muscle cells from iPSCs is to understand in vivo myogenic induction in development and regeneration. Current protocols of myogenic induction utilize techniques with overexpression of myogenic transcription factors such as Myod1(MyoD), Pax3, …Pax7, and others, using recombinant proteins or small molecules to induce mesodermal cells followed by myogenic progenitors, and adult muscle stem cells. This review summarizes the current approaches used for myogenic induction and highlights recent improvements. Show more

DOI: 10.3233/JND-200497

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 395-405, 2020

Authors: Batra, Abhinandan | Lott, Donovan J. | Willcocks, Rebecca | Forbes, Sean C. | Triplett, William | Dastgir, Jahannaz | Yun, Pomi | Reghan Foley, A. | Bönnemann, Carsten G. | Vandenborne, Krista | Walter, Glenn A.

Article Type: Research Article

Abstract: Collagen VI-related dystrophies (COL6-RDs) and Duchenne muscular dystrophy (DMD) cause progressive muscle weakness and disability. COL6-RDs are caused by mutations in the COL6 genes (COL6A1 , COL6A2 and COL6A3 ) encoding the extracellular matrix protein collagen VI, and DMD is caused by mutations in the DMD gene encoding the cytoplasmic protein dystrophin. Both COL6-RDs and DMD are characterized by infiltration of the muscles by fatty and fibrotic tissue. This study examined the effect of disease pathology on skeletal muscles in lower extremity muscles of COL6-RDs using timed functional tests, strength measures and qualitative/ quantitative magnetic resonance imaging/spectroscopy measures …(MRI/MRS) in comparison to unaffected (control) individuals. Patients with COL6-RD were also compared to age and gender matched patients with DMD. Patients with COL6-RD presented with a typical pattern of fatty infiltration of the muscle giving rise to an apparent halo effect around the muscle, while patients with DMD had evidence of fatty infiltration throughout the muscle areas imaged. Quantitatively, fat fraction, and transverse relaxation time (T2 ) were elevated in both COL6-RD and DMD patients compared to unaffected (control) individuals. Patients with COL6-RD had widespread muscle atrophy, likely contributing to weakness. In contrast, patients with DMD revealed force deficits even in muscle groups with increased contractile areas. Show more

Keywords: Collagen VI-related dystrophies, duchenne muscular dystrophy, magnetic resonance imaging, force production

DOI: 10.3233/JND-190457

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 407-417, 2020

Authors: Michaud, Maud | Stojkovic, Tanya | Maisonobe, Thierry | Behin, Anthony | Rucheton, Benoit | Léonard-Louis, Sarah | Eymard, Bruno | Laforêt, Pascal

Article Type: Research Article

Abstract: Neuropathies in Myoclonic Epilepsy with Ragged Red Fibers (MERRF) syndrome are frequent but ganglionopathies have never been reported. We retrospectively identified 24 patients with MERRF mutations in the neuromuscular center Nord/Est/Ile de France (Pitié-Salpêtrière, Paris, France). Seventeen nerve conduction studies (NCS) were available. Five patients had MERRF syndrome and ganglionopathy, a pure sensory neuropathy. All of them displayed ataxia and mild clinical sensory abnormalities. Ganglionopathies have been reported in mitochondrial diseases but never in MERRF syndrome. We suggest that patients presenting with ganglionopathy, especially if associated with myopathy, lipomatosis or epilepsy, should be screened for MERRF mutations.

Keywords: MERRF, ganglionopathy, ataxia, myopathy, dorsal root ganglia

DOI: 10.3233/JND-200513

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 419-423, 2020

Authors: Mori-Yoshimura, Madoka | Oya, Yasushi | Komaki, Hirohumi | Segawa, Kazuhiko | Minami, Narihiro | Saito, Yuko | Nishino, Ichizo | Takahashi, Yuji

Article Type: Research Article

Abstract: Background: Few studies have examined respiratory dysfunction in patients with Becker muscular dystrophy (BMD). Objective: This study aimed to examine the characteristics of respiratory dysfunction in patients with BMD. Methods: The present retrospective study assessed respiratory parameters of adult BMD patients using medical records and compared these parameters with various patient characteristics to identify correlations. BMD patients aged 17 years and older who had been diagnosed genetically and/or pathologically were included in the analysis. Results: Of the source population of 133 patients, respiratory function was assessed in 85. Two of these patients had no …symptoms, and eight had died. Mean % forced vital capacity (% FVC) was 94.2+/–21.7% (median, 96.1%; range, 5.1–134.1%). In 16 (19%) of the 85 patients, % FVC was <80%. Of these, seven were non-ambulant. Age, ambulation, and cardiac function did not significantly differ between patients with or without respiratory dysfunction, whereas age at onset was significantly lower in patients with respiratory dysfunction (7.7+/–4.7 years vs. 14.4+/–11.9 years; p  = 0.001). One non-ambulant patient was a continuous NPPV user, and one patient had been recommended NPPV use but refused. Autopsy of one patient revealed that the diaphragm and intercostal muscles were less affected than proximal skeletal muscles. Conclusion: BMD patients are at risk of developing respiratory dysfunction due to dystrophic changes in respiratory muscles. Respiratory function should be carefully and periodically monitored in these patients. Show more

Keywords: Becker muscular dystrophy (BMD), dystrophinopathy, respiratory dysfunction, cardiac function, genotype-phenotype correlation

DOI: 10.3233/JND-190438

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 425-431, 2020

Authors: Naarding, Karin J. | Doorenweerd, Nathalie | Koeks, Zaïda | Hendriksen, Ruben G.F. | Chotkan, Kinita A. | Krom, Yvonne D. | de Groot, Imelda J.M. | Straathof, Chiara S. | Niks, Erik H. | Kan, Hermien E.

Article Type: Research Article

Abstract: Background: Natural history data are essential for trial design in Duchenne (DMD) and Becker muscular dystrophy (BMD), but recruitment for observational studies can be challenging. Objective: We reviewed reasons why patients or caregivers declined participation, and compared characteristics of participants and non-participants to assess possible selection bias in four observational studies, three on DMD and one on BMD. Methods: Three pediatric DMD studies focused on cross-sectional cognitive function and brain MRI (DMDbrain, n  = 35 and DMDperfusion, n  = 12), and on longitudinal upper extremity function and muscle MRI (DMDarm, n  = 22). One adult BMD study assessed longitudinal …functioning (n  = 36). Considerations for non-participation were retrospectively reviewed from screening logs. Age, travel-time, DMD gene mutations and age at loss of ambulation (DMDarm and BMD study only), of participants and non-participants were derived from the Dutch Dystrophinopathy Database and compared using nonparametric tests (p  < 0.05). Results: The perceived burden of the protocol (38.2%), use of MRI (30.4%), and travel-time to the study site (19.1%) were the most frequently reported considerations for non-participation. Only few patients reported lack of personal gain (0.0– 5.9%). Overall, participating patients were representative for the studied sub-populations, except for a younger age of DMDarm study participants and a complete lack of participants with a mutation beyond exon 63. Conclusion: Optimizing patient involvement in protocol design, improving MRI experiences, and integrating research into clinics are important factors to decrease burden and facilitate participation. Nationwide registries are essential to compare participants and non-participants and ensure representative observational research. Specific effort is needed to include patients with distal mutations in cognitive studies. Show more

Keywords: Duchenne muscular dystrophy, becker muscular dystrophy, observational study, selection bias, magnetic resonance imaging, refusal to participate

DOI: 10.3233/JND-200541

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 433-442, 2020

Authors: Vázquez, José | Lefeuvre, Claire | Escobar, Rosa Elena | Luna Angulo, Alexandra Berenice | Miranda Duarte, Antonio | Delia Hernandez, Alma | Brisset, Marion | Carlier, Robert-Yves | Leturcq, France | Durand-Canard, Marie-Christine | Nicolas, Guillaume | Laforet, Pascal | Malfatti, Edoardo

Article Type: Research Article

Abstract: Background: Biallelic variants in Anoctamin 5 (ANO5 ) gene are causative of limb-girdle muscular dystrophy (LGMD) R12 anoctamin5-related, non-dysferlin Miyoshi-like distal myopathy (MMD3), and asymptomatic hyperCKemia. Objective: To describe clinic, histologic, genetic and imaging features, of ANO5 mutated patients. Methods: Five patients, four from France (P1, P2, P3 and P4) and one from Mexico (P5), from four families were included. P1 and P2, belonging to group 1, had normal muscle strength; Group 2, P3, P4 and P5, presented with muscular weakness. Muscle strength was measured by manual muscle testing, Medical Research Council (MRC) grades 1/5 …to 5/5. Laboratory exams included serum CK levels, nerve conduction studies (NCS)/needle electromyography (EMG), pulmonary function tests, EKG and cardiac ultrasound. ANO5 molecular screening was performed with different approaches. Results: Group 1 patients showed myalgias with hyperCKemia or isolated hyperCKemia. Group 2 patients presented with limb-girdle or proximo-distal muscular weakness. Serum CK levels ranged from 897 to 5000 UI/L. Muscle biopsy analysis in P4 and P5 showed subsarcolemmal mitochondrial aggregates. Electron microscopy confirmed mitochondrial proliferation and revealed discontinuity of the sarcolemmal membrane. Muscle MRI showed asymmetrical fibro-fatty substitution predominant in the lower limbs. P1 and P2 were compound heterozygous for c.191dupA (p.Asn64Lysfs*15) and c.1898 + G>A; P3 was homozygous for the c.692G>T. (p.Gly231Val); P4 harbored a novel biallelic homozygous exons 1–7 ANO5 gene deletion, and P5 was homozygous for a c.172 C > T (p.(Arg 58 Trp)) ANO5 pathogenic variant. Conclusions: Our cohort confirms the wide clinical variability and enlarge the genetic spectrum of ANO5-related myopathies. Show more

DOI: 10.3233/JND-200515

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 443-451, 2020

Authors: Aguerre, V. | De Castro, F. | Mozzoni, J. | Gravina, LP. | Araoz, HV. | Monges, S.

Article Type: Research Article

Abstract: Background: SMA1 natural history is characterized by early development of chronic respiratory failure. Respiratory interventions in type 1 SMA infants are subject to great practice variability. Nusinersen, has been recently approved in Argentina. The advent of novel treatments has highlighted the need for natural history studies reporting disease progression in type 1 SMA. Objective: To analyze the progression, respiratory interventions and survival based on the type of respiratory support in type 1SMA patients, in a third level pediatric hospital in Argentina. Methods: Cohort of SMA1 patients followed at the Interdisciplinary Program for the Study and Care …of Neuromuscular Patients (IPNM). Patient survival was analyzed by using the Kaplan-Meier method. Log-rank test was performed to compare the survival curve for three respiratory intervention groups. Results: 59 patients. Mean age of symptom onset was 2.19 (±1.4) months, age at diagnosis was 3.9 (±2.1) months. Patients developed respiratory failure at 5.82 months (±2.32) and 13.8 months (±5.6) in Type 1B and Type 1C, respectively (p  < 0.001) 53 p were SMA1B. Three copies were found in 1/6 SMA1C. Respiratory interventions: SRC 23 p (56.1%); SRC + NIV 8 p (19.5%); SRC + IV 10 p (24.4%). 8 patients were already on invasive ventilation when included in the IPNM. Patients with invasive ventilation showed longer survival. Conclusions: This series provides valuable information on respiratory intervention requirements and life expectancy in children with SMA1 before the implementation of novel treatments that increase the expression of the SMA protein. Show more

Keywords: Spinal muscular atrophy, infants

DOI: 10.3233/JND-200508

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 453-458, 2020

Authors: Rodriguez-Torres, Rafael | Fabiano, Julia | Goodwin, Ashley | Rao, Ashwini K. | Kinirons, Stacy | De Vivo, Darryl | Montes, Jacqueline

Article Type: Research Article

Abstract: Background: Individuals with spinal muscular atrophy (SMA) III walk independently, but experience muscle weakness, gait impairments, and fatigue. Although SMA affects proximal more than distal muscles, the characteristic pattern of selective muscle weakness has not been explained. Two theories have been proposed: 1) location of spinal motor neurons; and 2) differences in segmental innervation. Objective: To identify neuroanatomical models that explain the selective muscle weakness in individuals with SMA and assess the relationship of these models to ambulatory function. Methods: Data from 23 ambulatory SMA participants (78.2% male), ages 10–56 years, enrolled in two clinical studies …(NCT01166022, NCT02895789) were included. Strength was assessed using the Medical Research Council (MRC) score; ambulatory function was measured by distance walked on the 6-minute walk test (6 MWT). Three models were identified, and relationships assessed using Pearson correlation coefficients and linear regression. Results: All models demonstrated a positive association between strength and function, (p  < 0.02). Linear regression revealed that Model 3B, consisting of muscles innervated by lower lumbar and sacral segments, explained 67% of the variability observed in 6 MWT performance (β = 0.670, p  = 0.003). Conclusions: Muscles innervated by lower lumbar and sacral segments, i.e. hip extensors, hip abductors, knee flexors and ankle dorsiflexors, correlated with and predicted greater ambulatory function. The neuroanatomical patterns of muscle weakness may contribute to a better understanding of disease mechanisms and enable delivery of targeted therapies. Show more

Keywords: Spinal muscular atrophy, walking, muscle weakness, walk test, strength

DOI: 10.3233/JND-200550

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 459-466, 2020

Authors: Houwen-van Opstal, S.L.S. | van den Elzen, Y.M.E.M. | Jansen, M. | Willemsen, M.A.A.P. | Cup, E.H.C. | De Groot, I.J.M.

Article Type: Research Article

Abstract: Background: To retard shortening of finger flexors in patients with Duchenne muscular dystrophy (DMD), hand orthoses are prescribed. However, many patients do not wear the orthoses regularly. To optimize orthotic interventions, we need insight into the factors influencing compliance. Objective: To evaluate the compliance regarding hand orthoses in an adult DMD population and to explore experiences and perceptions of DMD patients wearing orthoses, and of their caregivers. Methods: Mixed methods observational study, combining quantitative and qualitative data from medical charts combined with qualitative semi-structured interviews using a constant comparative method and a short validated questionnaire (D-QUEST). …Results: 65 medical charts were analyzed. 48 patients were assessed as needing hand orthoses, of whom 37.5 % were compliant. Qualitative data analyses revealed (1) motivation: preservation of hand function; (2) barriers: discomfort and impediments; (3) facilitators: good fit and personalized wearing schedule; (4) fitting process: satisfactory, but patients do not readily seek help when barriers appear. Conclusions: Patients are motivated to wear hand orthoses, but often discontinue use because of orthosis-and disease-specific barriers. The identification of these barriers leads to practical and feasible recommendations concerning the orthoses and the fitting process, such as less rigid material, preservation of some function while wearing the orthoses, and fixed evaluation points. The findings were confirmed by the D-QUEST. Show more

Keywords: Duchenne muscular dystrophy, upper extremity, orthotic devices, splints, patient compliance, contracture

DOI: 10.3233/JND-200506

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 467-475, 2020

Authors: Savarese, Marco | Qureshi, Talha | Torella, Annalaura | Laine, Pia | Giugliano, Teresa | Jonson, Per Harald | Johari, Mridul | Paulin, Lars | Piluso, Giulio | Auvinen, Petri | Nigro, Vincenzo | Udd, Bjarne | Hackman, Peter

Article Type: Research Article

Abstract: Although DNA-sequencing is the most effective procedure to achieve a molecular diagnosis in genetic diseases, complementary RNA analyses are often required. Reverse-Transcription polymerase chain reaction (RT-PCR) is still a valuable option when the clinical phenotype and/or available DNA-test results address the diagnosis toward a gene of interest or when the splicing effect of a single variant needs to be assessed. We use Single-Molecule Real-Time sequencing to detect and characterize splicing defects and single nucleotide variants in well-known disease genes (DMD , NF1 , TTN ). After proper optimization, the procedure could be used in the diagnostic setting, simplifying …the workflow of cDNA analysis. Show more

Keywords: Long-read sequencing, single molecule real time, PacBio, splicing

DOI: 10.3233/JND-200523

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 477-481, 2020

Authors: Kroon, Rosemarie H.M.J.M. | Horlings, Corinne G.C. | de Swart, Bert J.M. | van Engelen, Baziel G.M. | Kalf, Johanna G.

Article Type: Research Article

Abstract: Background: Oculopharyngeal muscular dystrophy (OPMD) is a late onset progressive neuromuscular disorder. Although dysphagia is a pivotal sign in OPMD it is still not completely understood. Objective: The aim of this study was to systematically investigate oropharyngeal functioning in a large OPMD population. Methods: Forty-eight genetically confirmed OPMD patients completed questionnaires, performed clinical tests on swallowing, chewing, speaking, tongue strength and bite force, and underwent videofluoroscopy of swallowing. Descriptive statistics was used for all outcomes and logistic regression to investigate predictors of abnormal swallowing. Results: Eighty-two percent reported difficulties with swallowing, 27% with chewing …and 67% with speaking. Patients performed significantly worse on all oropharyngeal tests compared to age-matched controls except for bite force. Also asymptomatic carriers performed worse than controls: on chewing time, swallowing speed and articulation rate. During videofluoroscopy, all patients (except one asymptomatic) had abnormal residue and 19% aspirated. Independent predictors of abnormal residue were reduced swallowing capacity for thin liquids (OR 10 mL = 0.93; 20 mL = 0.95) and reduced tongue strength for thick liquids (OR 10 mL = 0.95); 20 mL = 0.90). Aspiration of thin liquids was predicted by disease duration (OR = 1.11) and post-swallow residue with 20 mL (OR = 4.03). Conclusion: Next to pharyngeal dysphagia, chewing and speaking are also frequently affected in OPMD patients, even in asymptomatic carriers. Residue after swallowing is a very early sign, while aspiration is a later sign in OPMD. For clinical follow-up monitoring of subjective complaints, swallowing capacity and tongue strength seems relevant. Show more

Keywords: Oculopharyngeal muscular dystrophy, dysphagia, dysarthria, neuromuscular diseases, cohort studies

DOI: 10.3233/JND-200511

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 483-494, 2020

Authors: Lassche, Saskia | Küsters, Benno | Heerschap, Arend | Schyns, Maxime V.P. | Ottenheijm, Coen A.C. | Voermans, Nicol C. | van Engelen, Baziel G.M.

Article Type: Research Article

Abstract: Background: Muscle MRI is increasingly used as a diagnostic and research tool in muscle disorders. However, the correlation between MRI abnormalities and histopathological severity is largely unknown. Objective: To investigate correlations between muscle MRI abnormalities and histopathological severity in healthy controls and patients with muscle disease. Methods: We performed quantitative MRI and histopathological analysis in 35 patients with inclusion body myositis, facioscapulohumeral muscular dystrophy or oculopharyngeal muscular dystrophy and 12 healthy controls. Participants contributed needle biopsies of the vastus lateralis and/or tibialis anterior, yielding 77 muscle biopsies with matched T1, T2 and TIRM MRI imaging. Muscle …biopsies were evaluated with a semi-quantitative histopathology severity grading scale (range 0–12) and an inflammation severity grading scale (range 0–3). Results: In muscle disease, histopathology sum scores ranged from 0 to 11 and correlated significantly with fat percentage as measured on MRI (Spearman’s rho = 0.594, p  < 0.001). Muscle edema on muscle MRI was associated with increased amounts of inflammation (p  < 0.001). Mild abnormalities occured in 95% of control biopsies and were more pronounced in tibialis anterior (median sum score of 1±1 in vastus lateralis and 2±1 in tibialis anterior (p  = 0.048)). Conclusion: In muscle disease, fatty infiltration on MRI correlates moderately with muscle histopathology. Histopathological abnormalities can occur prior to the onset of fatty infiltration. In middle-aged controls, almost all biopsies showed some histopathological abnormalities. The findings from this study may facilitate the choice for appropriate imaging sequences as outcome measures in therapeutic trials. Show more

Keywords: Magnetic resonance imaging, pathology, muscular dystrophies, inclusion body myositis

DOI: 10.3233/JND-200543

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 495-504, 2020

Authors: Benquey, T. | Fockens, E. | Kouton, L. | Delmont, E. | Martini, N. | Levy, N. | Attarian, S. | Bonello-Palot, N.

Article Type: Case Report

Abstract: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder commonly presenting with acute-onset, non-painful focal sensory and motor mono neuropathy. In 80% of cases, the genetic defect is a 1.5 Mb deletion on chromosome 17p11.2, including PMP22 . Only few cases of partial deletion and point mutations in PMP22 are involved in HNPP. We investigated a 62-years-old man with lower limb plexopathy first considered as Garland’s syndrome. A month later, his 29 years old son also consulted for paresthesia on the peroneal nerve. Targeted sequencing of the PMP22 gene identified a c.370delT (p.Trp124Glyfs*31) …in both affected patients. We report a new PMP22 point mutation associated with an atypical clinical phenotype of HNPP, a painful plexopathy of the lower limb worsenen by diabetes and a mere paresthesia, but a typical ENMG. This study illustrates the large spectrum of the disease, and emphasizes the importance of a complete ENMG and family history. Show more

Keywords: HNPP, PMP22 gene, point mutations, phenotypic heterogeneity

DOI: 10.3233/JND-190460

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 505-510, 2020

Authors: Peverelli, L. | De Rosa, A. | Domina, E. | Ciscato, P. | Sita, G. | Velardo, D. | Comi, G.P.

Article Type: Case Report

Abstract: Immune-related adverse events (irAE) during the administration of immune-checkpoint inhibitors (ICIs) become more evident due to the increased use of these therapies. To remind the importance of early recognition of this phenomenon, we report a paradigmatic case characterized by severe systemic inflammatory myopathy and severe cardiac involvement that abruptly precipitated in an untoward ending after one single dose of Pembrolizumab.

Keywords: Pembrolizumab, inflammatory myopathy, pulmonary carcinoma, immune-checkpoint inhibitors, immune-correlated adverse events

DOI: 10.3233/JND-200504

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 511-514, 2020

Authors: Kleefeld, Felix | Knebel, Fabian | Eurich, Dennis | Schatka, Imke | Blüthner, Elisabeth | Schönfeld, Shideh | Amthauer, Holger | Hahn, Katrin

Article Type: Case Report

Abstract: Hereditary transthyretin amyloidosis (hATTR amyloidosis) is a multisystemic disease usually presenting in a mixed neurological and cardiological phenotype. We present a case of hATTR amyloidosis associated with Leu55Arg mutation causing a form of familial oculo-leptomeningeal amyloidosis. Two brothers and their mother presented with severe autonomic neuropathy, loss of visual acuity and lepto-meningeal involvement. One patient suffered subarachnoid hemorrhage as a possible complication of cerebral involvement. The patients suffered from treatment-refractory weight loss and recurring vitreous opacities. RNA interference-based treatment has led to stabilization of autonomic and peripheral neuropathy but has had no effect on ocular symptoms.

Keywords: Transthyretin amyloidosis, FAP, hATTR, polyneuropathy

DOI: 10.3233/JND-200542

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 515-519, 2020

Authors: Bondi, Steven | Carroll, Elizabeth | Bhatt, Jaydeep

Article Type: Editorial

Abstract: Guillain-Barré Syndrome is a popular eponym that comes from a 1916 paper by Drs. Guillain, Barré, and Strohl. These physicians described two soldiers in the French Sixth Army during World War I who developed acute progressive motor weakness. Although Drs. Guillain and Barré have continued to be included in the syndrome’s eponym, Dr. Strohl has been forgotten despite having strongly contributed to the original paper. The reasons previously mentioned for Dr. Strohl’s absence appear trivial in contemporary practice and thus, his name deserves to be reintroduced to Guillain-Barré-Strohl Syndrome.

Keywords: History (Q000266), neurology (D009462)

DOI: 10.3233/JND-200545

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 521-522, 2020

Authors: Sansone, V.A. | Walter, M.C. | Attarian, S. | Delstanche, S. | Mercuri, E. | Lochmüller, H. | Neuwirth, C. | Vazquez-Costa, J.F. | Kleinschnitz, C. | Hagenacker, T.

Article Type: Meeting Report

Abstract: Spinal muscular atrophy (SMA) is a progressive autosomal recessive motor neuron disease which affects 1 in 6,000–10,000 live births, caused by loss of the survival motor neuron 1 gene (SMN1). A major focus of therapeutic developments has been on increasing the full-length SMN protein by increasing the inclusion of exon 7 in SMN2 transcripts, enhancing SMN2 gene expression, stabilizing the SMN protein or replacing the SMN1 gene. In June 2017, FDA and EMA have approved the antisense oligonucleotide Nusinersen as the first treatment for all SMA subtypes without age restriction. While prominent treatment effects have been observed in the …earlier stages of the disease and in patients up to 15 years of age, there is only limited data from clinical trials in adult SMA patients. First real-world data from neuromuscular clinical centers suggest a therapeutic benefit of nusinersen with a favourable safety profile also in adult SMA patients: in several cases, relevant improvements of motor function is achieved, which might lead to enhanced autonomy in daily life activities and improved quality of life. Systematic follow-up of the motor status with validated instruments is crucial for an adequate monitoring of the therapeutic effects but most of the widely used scales and scores have been developed and evaluated for the pediatric population only. International neuromuscular experts have met in Frankfurt/Main, Germany in May 2019 to discuss relevant aspects of the diagnostic pathway and patient management in adult SMA. The recommendations and challenges in this patient population are discussed. Show more

Keywords: 5q-SMA, adult SMA, spinal muscular atrophy, motor neuron, nusinersen

DOI: 10.3233/JND-200534

Citation: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 523-534, 2020