Journal of Neuromuscular Diseases - Volume 9, issue 5

Authors: Sjögreen, Lotta | Bengtsson, Lisa

Article Type: Research Article

Abstract: Background: The knowledge about the impact of oral motor impairment in neuromuscular diseases (NMDs) is limited but increasing. Objective: The aim of this review was to collect and compile knowledge on how muscle weakness in congenital or early developing NMDs directly or indirectly affects feeding, swallowing, speech and saliva control. Methods: A literature search was performed in PubMed from January 1, 1998, to August 31, 2021. The keywords “feeding”, “dysphagia”, “swallowing”, “dysarthria”, “speech”, “drooling” and “sialorrhea” were used in combination with “paediatric neuromuscular disease” or specific diagnoses. Results: Sixty-five studies were selected for the …review, 33 focused on feeding and swallowing, 11 on speech, four on a combination of feeding, swallowing, saliva control or speech and 17 general descriptions. Most of the studies reported on patients with a disorder affecting muscles. These studies show that muscle weakness and impaired motility affecting the muscles innervated by the cranial nerves may influence feeding, swallowing, and speech, and that respiratory function, general health and neurodevelopmental delay also influence these functions. Feeding impairment and breathing difficulties are common in NMDs. Lifesaving interventions such as tube feeding and ventilatory support are common in severe cases. Conclusions: Feeding impairment, dysphagia and dysarthria are prevalent in NMDs with congenital or early age of onset. Feeding and swallowing has been studied more than speech and saliva control. More children with NMD survive thanks to new treatment options and it is therefore urgent to follow up how these therapies may impact the development of feeding, swallowing, and speech. Show more

Keywords: Neuromuscular disease, feeding, speech, swallowing, dysarthria, dysphagia

DOI: 10.3233/JND-210772

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 581-596, 2022

Authors: Blaschek, Astrid | Kölbel, Heike | Schwartz, Oliver | Köhler, Cornelia | Gläser, Dieter | Eggermann, Katja | Hannibal, Iris | Schara-Schmidt, Ulrike | Müller-Felber, Wolfgang | Vill, Katharina

Article Type: Research Article

Abstract: Background: Early treatment after genetic newborn screening (NBS) for SMA significantly improves outcomes in infantile SMA. However, there is no consensus in the SMA treatment community about early treatment initiation in patients with four copies of SMN2 . Objective: Approach to a responsible treatment strategy for SMA patients with four SMN2 copies detected in newborn screening. Methods: Inclusion criteria were a history of SMA diagnosed by NBS, age > 12 months at last examination, and diagnosis of four SMN2 copies at confirmatory diagnosis. Results: 21 patients with SMA and four SMN2 copies were …identified in German screening projects over a three-year period. In three of them, the SMN2 copy number had to be corrected later, and three patients were lost to follow-up. Eight of the fifteen patients who were subject to long-term follow-up underwent presymptomatic therapy between 3 and 36 months of age and had no definite disease symptoms to date. Five of the other seven patients who underwent a strict follow-up strategy, showed clinical or electrophysiological disease onset between 1.5 and 4 years of age. In two of them, complete recovery was not achieved despite immediate initiation of treatment after the onset of the first symptoms. Conclusion: A remarkable proportion of patients with four copies of SMN2 develop irreversible symptoms within the first four years of life, if a wait-and-see strategy is followed. These data argue for a proactive approach, i.e., early initiation of treatment in this subgroup of SMA patients. Show more

Keywords: Spinal muscular atrophy, 4 SMN2 copies, outcome, newborn screening, presymptomatic treatment

DOI: 10.3233/JND-221510

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 597-605, 2022

Authors: Hiebeler, Miriam | Franke, Raimo | Ingenerf, Maria | Krause, Sabine | Mohassel, Payam | Pak, Katherine | Mammen, Andrew | Schoser, Benedikt | Bönnemann, Carsten G. | Walter, Maggie C.

Article Type: Research Article

Abstract: Background: Anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)-myopathy is a usually rapidly progressive form of immune-mediated necrotizing myopathy (IMNM). Rarer clinical courses show slow progression and resemble the phenotype of limb-girdle dystrophy (LGMD). Objective: We demonstrate the difficulties in differentiating LGMD versus anti-HMGCR-myopathy. Methods: We report on a 48-year-old patient with slowly progressive tetraparesis and hyperCKemia for more than 20 years. Results: Due to myopathic changes in initial and second muscle biopsy and typical clinical presentation, the patient was diagnosed with LGMD 20 years ago; despite comprehensive genetic testing including exome diagnostics, the genetic cause of disease could …not be identified. Finally, HMG-CoA reductase antibodies were detected, confirming the diagnosis of anti-HMGCR-myopathy. By re-work-up of a second muscle biopsy specimen from year 2009, the diagnosis of a IMNM was made in retrospect. Seven cycles of high-dose immunoglobulins were administered; patient reported outcome measures have mildly improved. Conclusion: Patients with clinical LGMD phenotype, degenerative changes in muscle biopsy but without genetic confirmation of the disease should be tested for HMG-CoA-myopathy, thereby allowing for an early start of treatment. Show more

Keywords: Limb-girdle dystrophy, anti-HMGCR-myopathy, muscle biopsy, immunoglobulins

DOI: 10.3233/JND-220810

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 607-614, 2022

Authors: Ashton, Catherine | Davis, Mark | Needham, Merrilee | Lamont, Phillipa

Article Type: Research Article

Abstract: A 38-year-old pregnant woman presented at 30 weeks gestation in respiratory distress with pre-eclampsia. This was on the background of slowly progressive dyspnoea over six years, with generalised weakness and previous surgery for ptosis and prognathia. After successful caesarean delivery at 31 weeks, the patient was found to have a homozygous likely pathogenic variant in the MYOD1 gene. This case presents a milder phenotype for MYOD1 congenital myopathy, usually associated with diaphragmatic defects, respiratory insufficiency and dysmorphic facies. It also highlights the difficulties of managing an undiagnosed patient through pregnancy.

Keywords: Myopathy, respiratory insufficiency, muscular disease, congenital myopathy

DOI: 10.3233/JND-210782

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 615-618, 2022

Authors: Takahashi, Junichiro | Mori-Yoshimura, Madoka | Ariga, Hajime | Sato, Noriko | Nishino, Ichizo | Takahashi, Yuji

Article Type: Research Article

Abstract: Purpose: Chilaiditi’s sign (CS), hepatodiaphragmatic interposition of the intestine, was caused by morphological abnormalities such as diaphragmatic atrophy, intestinal dilation, and liver atrophy. The sign is potentially important due to associations with clinically recurrent abdominal pain or even colonic volvulus. Late-onset Pompe disease (LOPD) could have the high prevalence of CS because of widened hepatodiaphragmatic space, following diaphragmatic atrophy, and the abnormal dilation of intestine caused by glycogen accumulation in smooth muscle of intestine. Our aim was to investigate the prevalence of CS in LOPD, and to identify the risk factors of CS in LOPD patients. Methods: Medical …records of genetically confirmed patients of Pompe disease at the National Center Hospital, National Center of Neurology and Psychiatry were retrospectively reviewed. We evaluated CS using chest X-ray (CXR) and abdominal CT and assessed the prevalence of CS in LOPD patients. We also divided the patients into two groups, CS and non-CS group, and evaluated the factor associated with CS compared to clinical variables between groups. Results: Three of seven (43%) were detected in CS. CS group (P5-7) and non-CS group (P1-4) were obtained. In comparison of clinical variables, the severity of atrophy in right diaphragms was significantly higher in CS than non-CS groups (p  = 0.029). Also, the frequency of abnormal position of right diaphragm and liver, and abnormally dilated bowel was seen in all of CS patients, but none of non-CS patient (p  = 0.029, each). Conclusion: In LOPD patients, the prevalence of CS was much higher of 43%, compared to healthy groups, or even in similarly respiratory muscle impaired neuromuscular diseases. The anatomically abnormal position of diaphragm and liver, atrophy and fat infiltration of diaphragms, and abnormally dilated bowel were significantly associated with CS in LOPD. We should pay more attention to CXR or abdominal CT as follow up in LOPD patients. Show more

Keywords: Late-onset Pompe disease, Chilaiditi’s sign, intestinal volvulus, non-invasive positive pressure ventilation, computed tomography, Chest X-Ray

DOI: 10.3233/JND-220792

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 619-627, 2022

Authors: Gallais, Benjamin | Roussel, Marie-Pier | Laberge, Luc | Hébert, Luc J. | Duchesne, Elise

Article Type: Research Article

Abstract: Background: Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disorder causing a plea of impairments, of which fatigue and apathy are some of the most frequent non-muscular symptoms. No curative treatment exists to date, and patients only have access to limited effective care, which are intended to decrease the burden of specific symptoms in daily life. Objective: This study aimed to assess whether a 12-week strength training program has an impact on fatigue/daytime sleepiness, apathy, and disease bruden in men with DM1. Methods: Eleven participants completed the Fatigue and Daytime Sleepiness Scale (FDSS) and the …Myotonic Dystrophy Health Index (MDHI) at baseline, at 6 and 12 weeks, and at 6 and 9 months. Also, the Apathy Evaluation Scale (AES) was filled out at baseline, at 12 weeks, and at 6 and 9 months. Results: Results show significant effects of the training program both on apathy and fatigue/daytime sleepiness, effects that are respectively greater at three and six months after the end of the program than at its very end. However, no difference was observed regarding the overall disease burden. Conclusion: These findings are promising for patients with DM1 considering that few non-pharmacological treatments are available. Show more

Keywords: Myotonic dystrophy, strength training, fatigue, excessive daytime sleepiness, apathy

DOI: 10.3233/JND-221503

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 629-639, 2022

Authors: Houwen-van Opstal, Saskia L.S. | Timmer, Amity C. | Ten Ham, A.M. | Hosman, Allard J.F. | Willemsen, Michel A.A.P. | de Groot, Imelda J.M.

Article Type: Research Article

Abstract: Background: Progressive equinovarus deformities are common in people with Duchenne Muscular Dystrophy (DMD); they may provoke pain, pressure spots, cause problems with wearing footwear, and may lead to an unstable sitting position. Objective: Explore indications and compare complications and long-term outcomes after soft tissue and osseous interventions in people with DMD. Methods: Retrospective, monocenter, longitudinal study. Data on indications, equinus and varus deformity before and after surgery, wound healing problems, ‘pain’, edema, and long-term outcomes were collected from medical files. Soft tissue interventions were compared with osseous interventions. Results: From a series of 18 …patients, data on 32 surgical interventions and 169 follow-up visits were analyzed. ‘Footrest placement’ was the most frequent surgical indication, followed by pain. Osseous interventions were performed in older patients with rigid deformities. Directly after surgery remaining deformities were reported after soft tissue interventions (18 %), no remaining deformities were reported after osseous interventions. Pain and edema were frequently present, especially after osseous surgery. Longitudinal follow-up showed that surgical interventions could lead to a neutral foot for a for more than 3 years on average years. Relapses of foot deformity occurred, especially the recurrence of varus deformity after osseous interventions. Conclusions: Surgical interventions can successfully lead to a neutral foot position for for more than 3 years on average. Soft tissue interventions appear to be superior to osseous corrections, considering the varus recurrence period and complications, and may be considered when feet are still (partly) correctable. Pain management and edema prevention should be anticipated before surgery. Future research on patient reported outcomes as well as evaluating the outcome of the initial indication is needed to further identify benefits. Show more

Keywords: Duchenne muscular dystrophy, foot deformity, orthopedic surgery, talectomy, tenotomy, arthrodesis, pain, edema

DOI: 10.3233/JND-220803

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 641-648, 2022

Authors: Pinto, Maria João | Fromes, Yves | Ackermann-Bonan, Isabelle | Leturcq, France | Verebi, Camille | Romero, Norma B. | Stojkovic, Tanya

Article Type: Research Article

Abstract:  Emery-Dreifuss Muscular Dystrophy (EDMD) is an early-onset, slowly-progressive group of myopathies, presenting with joint contractures, muscle weakness and cardiac abnormalities. Variants in the EMD gene cause an X-linked recessive form (EDMD1). The scarce EDMD1 muscle MRI accounts in the literature describe fatty replacement of posterior thigh and leg muscles. We report a 22-year-old patient with early-onset bilateral joint contractures, slowly progressive muscle weakness and minor cardiac rhythm abnormalities. A novel loss-of-function variant of EMD was identified and deemed probably pathogenic in the absence of emerin detection by immunofluorescence and Western Blot. MRI revealed fatty replacement of the lumbar spinal …erectors and the posterior compartment of lower limbs. Interestingly, Short Tau Inversion Recovery (STIR) sequences showed a heterogenous hyper signal on the vasti, hamstrings and left lateral gastrocnemius muscles. Oedema-like abnormalities were previously reported in early stages of other muscular dystrophies, preceding fatty replacement and muscle atrophy, but not in EDMD1 patients. We hypothesize that these oedema-like changes may be a marker of early muscle pathology in EDMD1. Further studies focusing on these abnormalities in the early phase of EDMD1 are required to test our hypothesis. Show more

Keywords: Myopathy, MRI hyperintensity, high signal, Emery-Dreifuss, emerin

DOI: 10.3233/JND-220823

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 649-654, 2022

Authors: Elman, Lauren | Youn, Bora | Proud, Crystal M. | Frey, Margaret R. | Ajroud-Driss, Senda | McCormick, M. Eileen | Michelson, David | Cartwright, Michael S. | Heiman-Patterson, Terry | Choi, Joseph M. | Chandak, Aastha | Khachatryan, Artak | Martinez, Marta | Paradis, Angela D.

Article Type: Short Communication

Abstract: Limited evidence exists on real-world adherence to nusinersen for the treatment of spinal muscular atrophy (SMA). Data are presented from a multi-site retrospective chart review of 86 adults with SMA initiating nusinersen at nine US centers between January 2017 and February 2019. Seventy-nine (92%) adults remained on nusinersen during the study; 454 (92%) of 493 total nusinersen doses were received on time. Fifty-eight (67%) adults received all nusinersen doses on time. The majority of patients with at least one nonadherent dose resumed nusinersen on time. Most patients followed the dosing schedule across the loading and maintenance dose periods.

Keywords: Medication adherence, spinal muscular atrophy, antisense oligonucleotides, neuromuscular diseases, retrospective studies, adults

DOI: 10.3233/JND-210768

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 655-660, 2022

Authors: Al Shehri, Ali | Al-Asmi, Abdullah | Al Salti, Abdullah Mohammed | Almadani, Abubaker | Hassan, Ali | Bamaga, Ahmed K. | Cupler, Edward J. | Al-Hashel, Jasem | Alabdali, Majed M. | Alanazy, Mohammed H. | Noori, Suzan

Article Type: Review Article

Abstract: Pompe disease is a rare, metabolic, autosomal recessive disorder. Early diagnosis is critical for progressive Pompe disease as delays can significantly alter the clinical course of the disease. Diagnostic modalities, including dried blood spot testing and genetic testing, are available and are effective for diagnosing patients with late-onset Pompe disease (LOPD). However, clinicians face numerous clinical challenges related to the diagnosis of the disease. Two expert group committee meetings, involving 11 experts from the United Arab Emirates, Kuwait, the Kingdom of Saudi Arabia, and Oman, were convened in October 2019 and November 2020 respectively to develop a uniform diagnostic algorithm …for the diagnosis of pediatric and adult LOPD in the Arabian Peninsula region. During the first meeting, the specialty-specific clinical presentation of LOPD was defined. During the second meeting, a diagnostic algorithm was developed after a thorough validation of clinical presentation or symptoms, which was performed with the aid of existing literature and expert judgement. A consensus was reached on the diagnostic algorithm for field specialists, such as neurologists, rheumatologists, general practitioners/internal medicine specialists, orthopedic specialists, and pulmonologists. This specialty-specific diagnostic referral algorithm for pediatric and adult LOPD will guide clinicians in the differential diagnosis of LOPD. Show more

Keywords: Late-onset Pompe disease, dried blood spot, Arabian Peninsula region, acid alpha-glucosidase

DOI: 10.3233/JND-220819

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 5, pp. 661-673, 2022