Karlijn Bouman, Frederik M A van den Heuvel, Reinder Evertz, Ewout Boesaard, Jan T Groothuis, Baziel G M van Engelen, Robin Nijveldt, Corrie E Erasmus, Floris E A Udink Ten Cate, Nicol C Voermans
Background: LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON-related myopathy (SELENON-RM) are two rare neuromuscular diseases characterized by proximal and axial muscle weakness, scoliosis, spinal rigidity, low bone quality and respiratory impairment. Cardiac involvement has previously been described in retrospective studies and case reports, but large case series and prospective studies in unselected cohorts are lacking.
Objective: The objective of this study is to conduct prevalence estimations, perform cardiac phenotyping, and provide recommendations for clinical care.
Methods: In this case series including two time points, we conducted comprehensive assessments with electrocardiography (ECG) and transthoracic echocardiography (TTE). ECGs were systematically assessed for a large subset of variables. TTE included left and right ventricular ejection fraction (LVEF/RVEF) and left ventricular global longitudinal strain (GLS), the latter being a more early and sensitive marker of left ventricular dysfunction.
Results: 21 LAMA2-MD (M = 5; 20±14 years) and 10 SELENON-RM patients (M = 7; 18±12 years) were included. In most patients, QRS fragmentation and Q waves, markers of heterogeneous ventricular activation, were present both at baseline and at follow-up. GLS was abnormal (age specific in children, > -18% in adults) in 33% of LAMA2-MD and 43% of SELENON-RM patients at baseline. Reduced LVEF (<52% in males, <54% in females and <55% in pediatric population) was observed in three LAMA2-MD patients at baseline and in none of the SELENON-RM patients. GLS and LVEF did not change between baseline and follow-up. RVEF was normal in all patients.
Conclusion: ECG abnormalities and abnormal GLS are prevalent in LAMA2-MD and SELENON-RM, yet abnormal LVEF was only seen in LAMA2-MD patients. One LAMA2-MD patient had a clinically relevant deterioration in LVEF during 1.5-year follow-up. We advise routine screening of all patients with LAMA2-MD or SELENON-RM with ECG and echocardiography at diagnosis, minimally every two years from second decade of life and if new cardiac signs arise.
{"title":"Cardiac Involvement in LAMA2-Related Muscular Dystrophy and SELENON-Related Congenital Myopathy: A Case Series.","authors":"Karlijn Bouman, Frederik M A van den Heuvel, Reinder Evertz, Ewout Boesaard, Jan T Groothuis, Baziel G M van Engelen, Robin Nijveldt, Corrie E Erasmus, Floris E A Udink Ten Cate, Nicol C Voermans","doi":"10.3233/JND-230190","DOIUrl":"10.3233/JND-230190","url":null,"abstract":"<p><strong>Background: </strong>LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON-related myopathy (SELENON-RM) are two rare neuromuscular diseases characterized by proximal and axial muscle weakness, scoliosis, spinal rigidity, low bone quality and respiratory impairment. Cardiac involvement has previously been described in retrospective studies and case reports, but large case series and prospective studies in unselected cohorts are lacking.</p><p><strong>Objective: </strong>The objective of this study is to conduct prevalence estimations, perform cardiac phenotyping, and provide recommendations for clinical care.</p><p><strong>Methods: </strong>In this case series including two time points, we conducted comprehensive assessments with electrocardiography (ECG) and transthoracic echocardiography (TTE). ECGs were systematically assessed for a large subset of variables. TTE included left and right ventricular ejection fraction (LVEF/RVEF) and left ventricular global longitudinal strain (GLS), the latter being a more early and sensitive marker of left ventricular dysfunction.</p><p><strong>Results: </strong>21 LAMA2-MD (M = 5; 20±14 years) and 10 SELENON-RM patients (M = 7; 18±12 years) were included. In most patients, QRS fragmentation and Q waves, markers of heterogeneous ventricular activation, were present both at baseline and at follow-up. GLS was abnormal (age specific in children, > -18% in adults) in 33% of LAMA2-MD and 43% of SELENON-RM patients at baseline. Reduced LVEF (<52% in males, <54% in females and <55% in pediatric population) was observed in three LAMA2-MD patients at baseline and in none of the SELENON-RM patients. GLS and LVEF did not change between baseline and follow-up. RVEF was normal in all patients.</p><p><strong>Conclusion: </strong>ECG abnormalities and abnormal GLS are prevalent in LAMA2-MD and SELENON-RM, yet abnormal LVEF was only seen in LAMA2-MD patients. One LAMA2-MD patient had a clinically relevant deterioration in LVEF during 1.5-year follow-up. We advise routine screening of all patients with LAMA2-MD or SELENON-RM with ECG and echocardiography at diagnosis, minimally every two years from second decade of life and if new cardiac signs arise.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H Willemijn van Bruggen, Camiel A Wijngaarde, Faylynn Asselman, Marloes Stam, Nico H J Creugers, Renske I Wadman, W Ludo van der Pol, Stanimira I Kalaykova
Background: Hereditary proximal spinal muscular atrophy (SMA) is characterized by abnormal alpha motor neuron function in brainstem and spinal cord. Bulbar dysfunction, including limited mouth opening, is present in the majority of patients with SMA but it is unknown if and how these problems change during disease course.
Objective: In this prospective, observational, longitudinal natural history study we aimed to study bulbar dysfunction in patients with SMA types 2 and 3.
Methods: We included 44 patients with SMA types 2 and 3 (mean age was 33.6 (95% CI 28.4;38.9) and re-examined them after on average 4 years. None were treated with SMN-modulating treatments before or during the course of this study. Longitudinal assessments included a questionnaire on mandibular and bulbar function, the Mandibular Function Impairment Questionnaire (MFIQ), and a clinical examination of masticatory performance, maximum voluntary bite force, and mandibular movements including the active maximal mouth opening.
Results: We found significant higher MFIQ scores and a significant decrease of all mandibular movements in patients with SMA type 2 (p < 0.001), but not in SMA type 3. Masticatory performance and maximum voluntary bite force did not change significantly. Mean reduction of active maximal mouth opening at follow-up was 3.5 mm in SMA type 2 (95% CI: 2.3; 4.7, p < 0.001). SMA type 2 was an independent predictor for a more severe reduction of the mouth opening (β= -2.0 mm (95% CI: -3.8; -0.1, p = 0.043)).
Conclusions: Bulbar functions such as mandibular mobility and active maximum mouth opening decrease significantly over the course of four years in patients with SMA type 2.
背景:遗传性近端脊髓性肌萎缩症(SMA)的特点是脑干和脊髓α运动神经元功能异常。大多数 SMA 患者都会出现口部功能障碍,包括张口受限,但这些问题在病程中是否会发生变化以及如何变化尚不清楚:在这项前瞻性、观察性、纵向自然史研究中,我们旨在研究 SMA 2 型和 3 型患者的球部功能障碍:我们纳入了 44 名 SMA 2 型和 3 型患者(平均年龄为 33.6 岁(95% CI 28.4;38.9)),并在平均 4 年后对他们进行了复查。在本研究之前或期间,没有人接受过 SMN 调节治疗。纵向评估包括下颌和球部功能问卷、下颌功能损害问卷(MFIQ)以及咀嚼功能、最大自主咬合力和下颌运动(包括主动最大张口)的临床检查:我们发现,SMA 2 型患者的 MFIQ 分数明显较高,所有下颌运动均明显减少(p < 0.001),而 SMA 3 型患者则没有。咀嚼功能和最大自主咬合力没有明显变化。随访时,SMA 2 型患者主动最大张口度的平均减少量为 3.5 mm(95% CI:2.3; 4.7,p < 0.001)。结论:SMA 2 型是导致张口度更严重降低的独立预测因素(β= -2.0 mm (95% CI: -3.8; -0.1, p = 0.043)):结论:SMA 2 型患者的下颌骨活动度和主动最大张口度等球部功能在四年内显著下降。
{"title":"Natural History of Mandibular Function in Spinal Muscular Atrophy Types 2 and 3.","authors":"H Willemijn van Bruggen, Camiel A Wijngaarde, Faylynn Asselman, Marloes Stam, Nico H J Creugers, Renske I Wadman, W Ludo van der Pol, Stanimira I Kalaykova","doi":"10.3233/JND-240007","DOIUrl":"10.3233/JND-240007","url":null,"abstract":"<p><strong>Background: </strong>Hereditary proximal spinal muscular atrophy (SMA) is characterized by abnormal alpha motor neuron function in brainstem and spinal cord. Bulbar dysfunction, including limited mouth opening, is present in the majority of patients with SMA but it is unknown if and how these problems change during disease course.</p><p><strong>Objective: </strong>In this prospective, observational, longitudinal natural history study we aimed to study bulbar dysfunction in patients with SMA types 2 and 3.</p><p><strong>Methods: </strong>We included 44 patients with SMA types 2 and 3 (mean age was 33.6 (95% CI 28.4;38.9) and re-examined them after on average 4 years. None were treated with SMN-modulating treatments before or during the course of this study. Longitudinal assessments included a questionnaire on mandibular and bulbar function, the Mandibular Function Impairment Questionnaire (MFIQ), and a clinical examination of masticatory performance, maximum voluntary bite force, and mandibular movements including the active maximal mouth opening.</p><p><strong>Results: </strong>We found significant higher MFIQ scores and a significant decrease of all mandibular movements in patients with SMA type 2 (p < 0.001), but not in SMA type 3. Masticatory performance and maximum voluntary bite force did not change significantly. Mean reduction of active maximal mouth opening at follow-up was 3.5 mm in SMA type 2 (95% CI: 2.3; 4.7, p < 0.001). SMA type 2 was an independent predictor for a more severe reduction of the mouth opening (β= -2.0 mm (95% CI: -3.8; -0.1, p = 0.043)).</p><p><strong>Conclusions: </strong>Bulbar functions such as mandibular mobility and active maximum mouth opening decrease significantly over the course of four years in patients with SMA type 2.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Payam Mohassel, Meher Abdullah, Florian S Eichler, Teresa M Dunn
Motor neuron diseases and peripheral neuropathies are heterogeneous groups of neurodegenerative disorders that manifest with distinct symptoms due to progressive dysfunction or loss of specific neuronal subpopulations during different stages of development. A few monogenic, neurodegenerative diseases associated with primary metabolic disruptions of sphingolipid biosynthesis have been recently discovered. Sphingolipids are a subclass of lipids that form critical building blocks of all cellular and subcellular organelle membranes including the membrane components of the nervous system cells. They are especially abundant within the lipid portion of myelin. In this review, we will focus on our current understanding of disease phenotypes in three monogenic, neuromuscular diseases associated with pathogenic variants in components of serine palmitoyltransferase, the first step in sphingolipid biosynthesis. These include hereditary sensory and autonomic neuropathy type 1 (HSAN1), a sensory predominant peripheral neuropathy, and two neurodegenerative disorders: juvenile amyotrophic lateral sclerosis affecting the upper and lower motor neurons with sparing of sensory neurons, and a complicated form of hereditary spastic paraplegia with selective involvement of the upper motor neurons and more broad CNS neurodegeneration. We will also review our current understanding of disease pathomechanisms, therapeutic approaches, and the unanswered questions to explore in future studies.
{"title":"Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.","authors":"Payam Mohassel, Meher Abdullah, Florian S Eichler, Teresa M Dunn","doi":"10.3233/JND-240014","DOIUrl":"10.3233/JND-240014","url":null,"abstract":"<p><p>Motor neuron diseases and peripheral neuropathies are heterogeneous groups of neurodegenerative disorders that manifest with distinct symptoms due to progressive dysfunction or loss of specific neuronal subpopulations during different stages of development. A few monogenic, neurodegenerative diseases associated with primary metabolic disruptions of sphingolipid biosynthesis have been recently discovered. Sphingolipids are a subclass of lipids that form critical building blocks of all cellular and subcellular organelle membranes including the membrane components of the nervous system cells. They are especially abundant within the lipid portion of myelin. In this review, we will focus on our current understanding of disease phenotypes in three monogenic, neuromuscular diseases associated with pathogenic variants in components of serine palmitoyltransferase, the first step in sphingolipid biosynthesis. These include hereditary sensory and autonomic neuropathy type 1 (HSAN1), a sensory predominant peripheral neuropathy, and two neurodegenerative disorders: juvenile amyotrophic lateral sclerosis affecting the upper and lower motor neurons with sparing of sensory neurons, and a complicated form of hereditary spastic paraplegia with selective involvement of the upper motor neurons and more broad CNS neurodegeneration. We will also review our current understanding of disease pathomechanisms, therapeutic approaches, and the unanswered questions to explore in future studies.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
There has been tremendous progress in treatment of neuromuscular diseases over the last 20 years, which has transformed the natural history of these severely debilitating conditions. Although the factors that determine the response to therapy are many and in some instance remain to be fully elucidated, early treatment clearly has a major impact on patient outcomes across a number of inherited neuromuscular conditions. To improve patient care and outcomes, clinicians should be aware of neuromuscular conditions that require prompt treatment initiation. This review describes data that underscore the importance of early treatment of children with inherited neuromuscular conditions with an emphasis on data resulting from newborn screening efforts.
{"title":"The Importance of Early Treatment of Inherited Neuromuscular Conditions.","authors":"Laurane Mackels, Laurent Servais","doi":"10.3233/JND-230189","DOIUrl":"10.3233/JND-230189","url":null,"abstract":"<p><p>There has been tremendous progress in treatment of neuromuscular diseases over the last 20 years, which has transformed the natural history of these severely debilitating conditions. Although the factors that determine the response to therapy are many and in some instance remain to be fully elucidated, early treatment clearly has a major impact on patient outcomes across a number of inherited neuromuscular conditions. To improve patient care and outcomes, clinicians should be aware of neuromuscular conditions that require prompt treatment initiation. This review describes data that underscore the importance of early treatment of children with inherited neuromuscular conditions with an emphasis on data resulting from newborn screening efforts.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Walaa Karazi, Jacqueline Coppers, Daphne Maas, Edith Cup, Bart Bloemen, Nicole Voet, Jan T Groothuis, Tomàs Pinós, Ramon Marti Seves, Ros Quinlivan, Nicoline Løkken, John Vissing, Salman Bhai, Andrew Wakelin, Stacey Reason, Nicol C Voermans
Background: Glycogen storage disease type 5 (GSD) is an autosomal recessive inherited metabolic myopathy caused by a deficiency of the enzyme muscle glycogen phosphorylase. Individuals with GSD5 experience physical activity intolerance.
Objective: This patient-led study aimed to capture the daily life experiences of GSD5, with a focus on adapting to and coping with their physical activity intolerance.
Methods: An online survey was composed in close collaboration with patient organizations. It consisted of customized and validated questionnaires on demographics, general health and comorbidities, physical activity, psychosocial well-being and functioning, pain, fatigue and adapting to and coping with GSD5.
Results: One hundred sixty-two participants (16 countries) participated. The majority, n = 86 (69%) were from the Netherlands, USA or UK. We observed a high rate of misdiagnosis prior to GSD5 diagnosis (49%), surprisingly a relatively high proportion had not been diagnosed by DNA testing which is the gold standard. Being diagnosed had a strong impact on emotional status, daily life activities and important life choices. A large proportion had not received any rehabilitation (41%) nor medical treatment (57%) before diagnosis. Engagement in vigorous and moderate physical activity was reduced. Health related quality of life was low, most likely related to low physical health. The median Fatigue Severity Score was 4.3, indicating moderate to severe fatigue. Participants themselves had found various ways to adapt to and cope with their disability. The adaptations concerned all aspect of their life, including household chores, social and physical activities, and work. In addition to lack of support, participants reported limited availability of information sources.
Conclusion: Participants have provided guidance for newly diagnosed people, including the advice to accept one's limited abilities and maintain an active lifestyle. We conclude that adequate counseling on ways of adapting and coping is expected to increase both health-related quality of life and physical activity.
{"title":"Toward an Understanding of GSD5 (McArdle disease): How Do Individuals Learn to Live with the Metabolic Defect in Daily Life.","authors":"Walaa Karazi, Jacqueline Coppers, Daphne Maas, Edith Cup, Bart Bloemen, Nicole Voet, Jan T Groothuis, Tomàs Pinós, Ramon Marti Seves, Ros Quinlivan, Nicoline Løkken, John Vissing, Salman Bhai, Andrew Wakelin, Stacey Reason, Nicol C Voermans","doi":"10.3233/JND-230027","DOIUrl":"10.3233/JND-230027","url":null,"abstract":"<p><strong>Background: </strong>Glycogen storage disease type 5 (GSD) is an autosomal recessive inherited metabolic myopathy caused by a deficiency of the enzyme muscle glycogen phosphorylase. Individuals with GSD5 experience physical activity intolerance.</p><p><strong>Objective: </strong>This patient-led study aimed to capture the daily life experiences of GSD5, with a focus on adapting to and coping with their physical activity intolerance.</p><p><strong>Methods: </strong>An online survey was composed in close collaboration with patient organizations. It consisted of customized and validated questionnaires on demographics, general health and comorbidities, physical activity, psychosocial well-being and functioning, pain, fatigue and adapting to and coping with GSD5.</p><p><strong>Results: </strong>One hundred sixty-two participants (16 countries) participated. The majority, n = 86 (69%) were from the Netherlands, USA or UK. We observed a high rate of misdiagnosis prior to GSD5 diagnosis (49%), surprisingly a relatively high proportion had not been diagnosed by DNA testing which is the gold standard. Being diagnosed had a strong impact on emotional status, daily life activities and important life choices. A large proportion had not received any rehabilitation (41%) nor medical treatment (57%) before diagnosis. Engagement in vigorous and moderate physical activity was reduced. Health related quality of life was low, most likely related to low physical health. The median Fatigue Severity Score was 4.3, indicating moderate to severe fatigue. Participants themselves had found various ways to adapt to and cope with their disability. The adaptations concerned all aspect of their life, including household chores, social and physical activities, and work. In addition to lack of support, participants reported limited availability of information sources.</p><p><strong>Conclusion: </strong>Participants have provided guidance for newly diagnosed people, including the advice to accept one's limited abilities and maintain an active lifestyle. We conclude that adequate counseling on ways of adapting and coping is expected to increase both health-related quality of life and physical activity.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bettine A H Vosse, Jasmijn de Jong, Leandre A la Fontaine, Corinne G C Horlings, Sander M J van Kuijk, Nicolle A M Cobben, Anne-Fleur Domensino, Caroline van Heugten, Catharina G Faber
Background: Chronic respiratory failure often occurs in myotonic dystrophy type 1 (DM1) and can be treated with noninvasive home mechanical ventilation (HMV). Treatment adherence with HMV is often suboptimal in patients with DM1, but the reasons for that are not well understood.
Objective: The aim of this exploratory study was to gain insight in the prevalence of mild cognitive impairment, affective symptoms, and apathy and to investigate their role in HMV treatment adherence in DM1.
Methods: The Montreal Cognitive Assessment (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Apathy Evaluation Scale (AES) were used to assess cognition, affective symptoms, and apathy in DM1 patients that use HMV. Patients with low treatment adherence (average daily use HMV <5 h or <80% of the days) were compared with patients with high treatment adherence (average daily use of HMV≥5 h and ≥80% of the days).
Results: Sixty patients were included. Abnormal scores were found in 40% of the total group for the MoCA, in 72-77% for the AES, and in 18% for HADS depression. There was no difference between the high treatment adherence group (n = 39) and the low treatment adherence group (n = 21) for the MoCA, AES, and HADS depression. The HADS anxiety was abnormal in 30% of the total group, and was significantly higher in the low treatment adherence group (p = 0.012). Logistic regression analysis revealed that a higher age and a higher BMI were associated with a greater chance of high treatment adherence.
Conclusions: This exploratory study showed that cognitive impairment and apathy are frequently present in DM1 patients that use HMV, but they are not associated with treatment adherence. Feelings of anxiety were associated with low treatment adherence. Higher age and higher BMI were associated with high treatment adherence with HMV.
{"title":"The Role of Cognition, Affective Symptoms, and Apathy in Treatment Adherence with Noninvasive Home Mechanical Ventilation in Myotonic Dystrophy.","authors":"Bettine A H Vosse, Jasmijn de Jong, Leandre A la Fontaine, Corinne G C Horlings, Sander M J van Kuijk, Nicolle A M Cobben, Anne-Fleur Domensino, Caroline van Heugten, Catharina G Faber","doi":"10.3233/JND-240081","DOIUrl":"10.3233/JND-240081","url":null,"abstract":"<p><strong>Background: </strong>Chronic respiratory failure often occurs in myotonic dystrophy type 1 (DM1) and can be treated with noninvasive home mechanical ventilation (HMV). Treatment adherence with HMV is often suboptimal in patients with DM1, but the reasons for that are not well understood.</p><p><strong>Objective: </strong>The aim of this exploratory study was to gain insight in the prevalence of mild cognitive impairment, affective symptoms, and apathy and to investigate their role in HMV treatment adherence in DM1.</p><p><strong>Methods: </strong>The Montreal Cognitive Assessment (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Apathy Evaluation Scale (AES) were used to assess cognition, affective symptoms, and apathy in DM1 patients that use HMV. Patients with low treatment adherence (average daily use HMV <5 h or <80% of the days) were compared with patients with high treatment adherence (average daily use of HMV≥5 h and ≥80% of the days).</p><p><strong>Results: </strong>Sixty patients were included. Abnormal scores were found in 40% of the total group for the MoCA, in 72-77% for the AES, and in 18% for HADS depression. There was no difference between the high treatment adherence group (n = 39) and the low treatment adherence group (n = 21) for the MoCA, AES, and HADS depression. The HADS anxiety was abnormal in 30% of the total group, and was significantly higher in the low treatment adherence group (p = 0.012). Logistic regression analysis revealed that a higher age and a higher BMI were associated with a greater chance of high treatment adherence.</p><p><strong>Conclusions: </strong>This exploratory study showed that cognitive impairment and apathy are frequently present in DM1 patients that use HMV, but they are not associated with treatment adherence. Feelings of anxiety were associated with low treatment adherence. Higher age and higher BMI were associated with high treatment adherence with HMV.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlotte Colot, Sarah Benmechri, Elke Everaert, Sarah Muys, Linde Van Himme, Valentine Tahon, Maurine Salmon, Dorine Van Dyck, Elke De Vos, Nicolas Deconinck
Background: Spinal muscular atrophy (SMA), a genetic neuromuscular disease caused by lack of survival of motor neuron (SMN) protein, is characterized by muscular atrophy and respiratory and bulbar dysfunction. While swallowing disorders are common, they remain poorly studied.
Objectives: Our study aimed to explore 1) intraoral pressure measurements with the Iowa Oral Performance Instrument system and the reliability of a Swallowing Function Assessment Questionnaire (SFAQ) in healthy controls, and 2) evaluate their use as swallowing function biomarkers and the evolution of swallowing function over time in children with SMA.
Methods: We recruited 53 healthy children and 27 SMA patients all treated with SMN gene modulator therapy. Participants completed the SFAQ and underwent at least one measurement of maximal oral pressures (lingual, labial, and masseter).
Results: Mean oral normalized pressure index were lower (all sites p < 0.001) and mean SFAQ scores were higher (p < 0.001) in patients compared with healthy controls. Pressure evolution over 1 year in SMA patients for all three oral sites did not show significant differences. SFAQ scores correlated negatively with oral pressures at all three sites in patients.
Conclusions: Both tools provided new insights on the oral and pharyngeal phase of swallowing in SMA patients. In SMA patients, muscle strength in certain crucial anatomical regions during swallowing is weaker than in healthy children.
背景:脊髓性肌萎缩症(SMA)是一种遗传性神经肌肉疾病,因运动神经元(SMN)蛋白缺乏存活能力而引起,以肌肉萎缩、呼吸和球部功能障碍为特征。虽然吞咽障碍很常见,但对其的研究仍然很少:我们的研究旨在探讨:1)在健康对照组中使用爱荷华口腔表现仪器系统测量口腔内压力和吞咽功能评估问卷(SFAQ)的可靠性;2)评估它们作为吞咽功能生物标志物的使用情况以及 SMA 儿童吞咽功能随时间的变化情况:我们招募了 53 名健康儿童和 27 名 SMA 患者,他们均接受过 SMN 基因调节剂治疗。参与者完成了 SFAQ,并接受了至少一次最大口腔压力(舌压、唇压和颌下肌压)测量:结果:平均口腔正常化压力指数较低(所有部位均为 P这两种工具为了解 SMA 患者的口腔和咽部吞咽阶段提供了新的视角。与健康儿童相比,SMA 患者在吞咽过程中某些关键解剖区域的肌肉力量较弱。
{"title":"Assessing the Swallowing Function in Children with Spinal Muscular Atrophy: An Easily Accessible and Objective Multidimensional Approach.","authors":"Charlotte Colot, Sarah Benmechri, Elke Everaert, Sarah Muys, Linde Van Himme, Valentine Tahon, Maurine Salmon, Dorine Van Dyck, Elke De Vos, Nicolas Deconinck","doi":"10.3233/JND-240017","DOIUrl":"10.3233/JND-240017","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA), a genetic neuromuscular disease caused by lack of survival of motor neuron (SMN) protein, is characterized by muscular atrophy and respiratory and bulbar dysfunction. While swallowing disorders are common, they remain poorly studied.</p><p><strong>Objectives: </strong>Our study aimed to explore 1) intraoral pressure measurements with the Iowa Oral Performance Instrument system and the reliability of a Swallowing Function Assessment Questionnaire (SFAQ) in healthy controls, and 2) evaluate their use as swallowing function biomarkers and the evolution of swallowing function over time in children with SMA.</p><p><strong>Methods: </strong>We recruited 53 healthy children and 27 SMA patients all treated with SMN gene modulator therapy. Participants completed the SFAQ and underwent at least one measurement of maximal oral pressures (lingual, labial, and masseter).</p><p><strong>Results: </strong>Mean oral normalized pressure index were lower (all sites p < 0.001) and mean SFAQ scores were higher (p < 0.001) in patients compared with healthy controls. Pressure evolution over 1 year in SMA patients for all three oral sites did not show significant differences. SFAQ scores correlated negatively with oral pressures at all three sites in patients.</p><p><strong>Conclusions: </strong>Both tools provided new insights on the oral and pharyngeal phase of swallowing in SMA patients. In SMA patients, muscle strength in certain crucial anatomical regions during swallowing is weaker than in healthy children.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sam Geuens, Nathalie Goemans, Jurgen Lemiere, Nathalie Doorenweerd, Liesbeth De Waele
Background: Emerging evidence underscores the high prevalence of neurobehavioral difficulties like ADHD, ASD and OCD, in patients with Duchenne muscular dystrophy (DMD). The substantial impact of these complex behavioral challenges in addition to motor function decline on the well-being of affected individuals and their families is increasingly evident. However, a uniform approach for effective screening, assessment and management of the neurobehavioral symptoms remains elusive.
Objective: We explored strategies used by healthcare professionals with clinical expertise in DMD to address neurobehavioral symptoms, in order to uncover diverse practices and to identify potential directions for clinical approaches in managing DMD neurobehavioral symptoms.
Methods and results: Twenty-eight respondents from 16 different countries completed an online survey. Only 35% of the centers systematically screened for neurobehavioral difficulties in their DMD population. Predominant screening methods included history taking and clinical observation. Common neurobehavioral difficulties encompassed learning challenges, dependency from adults, anxiety, concentration difficulties, and social deficits. The participating centers frequently employed parental counseling and liaison with psychosocial healthcare professionals for psychosocial intervention.
Conclusion: This study underscores the complex behavioral landscape in DMD, highlighting the need for validated screening, assessment and management strategies and collaborative efforts in implementing these. We advocate for international consensus recommendations for screening, assessment and management of neurobehavioral difficulties in DMD to enhance patient care and communication across healthcare settings.
{"title":"Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties: Insights from Clinical Practice.","authors":"Sam Geuens, Nathalie Goemans, Jurgen Lemiere, Nathalie Doorenweerd, Liesbeth De Waele","doi":"10.3233/JND-230251","DOIUrl":"10.3233/JND-230251","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence underscores the high prevalence of neurobehavioral difficulties like ADHD, ASD and OCD, in patients with Duchenne muscular dystrophy (DMD). The substantial impact of these complex behavioral challenges in addition to motor function decline on the well-being of affected individuals and their families is increasingly evident. However, a uniform approach for effective screening, assessment and management of the neurobehavioral symptoms remains elusive.</p><p><strong>Objective: </strong>We explored strategies used by healthcare professionals with clinical expertise in DMD to address neurobehavioral symptoms, in order to uncover diverse practices and to identify potential directions for clinical approaches in managing DMD neurobehavioral symptoms.</p><p><strong>Methods and results: </strong>Twenty-eight respondents from 16 different countries completed an online survey. Only 35% of the centers systematically screened for neurobehavioral difficulties in their DMD population. Predominant screening methods included history taking and clinical observation. Common neurobehavioral difficulties encompassed learning challenges, dependency from adults, anxiety, concentration difficulties, and social deficits. The participating centers frequently employed parental counseling and liaison with psychosocial healthcare professionals for psychosocial intervention.</p><p><strong>Conclusion: </strong>This study underscores the complex behavioral landscape in DMD, highlighting the need for validated screening, assessment and management strategies and collaborative efforts in implementing these. We advocate for international consensus recommendations for screening, assessment and management of neurobehavioral difficulties in DMD to enhance patient care and communication across healthcare settings.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-HMGCR myopathy is decribed as an immune-mediated necrotizing myopathy which is characterised by subacute, progressive proximal muscle weakness and elevated creatine kinase (CK) level. In pediatric population, anti-HMGCR myopathy has been reported solely as small case reports, albeit rare. Although treatment consensus has not yet been established, proper treatment with several immunomodulators to include IVIg can show remarkable improvement. We report an 11-year-old-girl diagnosed with anti-HMGCR myopathy with 6 years of follow-up.
{"title":"Six Years Follow-Up of an 11-Year-Old Girl with Anti-HMGCR Myopathy.","authors":"Dilek Cavusoglu, Beril Talim, Gazanfer Ekinci, Haluk Topaloglu","doi":"10.3233/JND-240022","DOIUrl":"10.3233/JND-240022","url":null,"abstract":"<p><p>Anti-HMGCR myopathy is decribed as an immune-mediated necrotizing myopathy which is characterised by subacute, progressive proximal muscle weakness and elevated creatine kinase (CK) level. In pediatric population, anti-HMGCR myopathy has been reported solely as small case reports, albeit rare. Although treatment consensus has not yet been established, proper treatment with several immunomodulators to include IVIg can show remarkable improvement. We report an 11-year-old-girl diagnosed with anti-HMGCR myopathy with 6 years of follow-up.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luca Bello, Daniele Sabbatini, Aurora Fusto, Domenico Gorgoglione, Giovanni Umberto Borin, Martina Penzo, Pietro Riguzzi, Matteo Villa, Sara Vianello, Chiara Calore, Paola Melacini, Riccardo Vio, Andrea Barp, Grazia D'Angelo, Sandra Gandossini, Luisa Politano, Angela Berardinelli, Sonia Messina, Gian Luca Vita, Marina Pedemonte, Claudio Bruno, Emilio Albamonte, Valeria Sansone, Giovanni Baranello, Riccardo Masson, Guja Astrea, Adele D'Amico, Enrico Bertini, Marika Pane, Simona Lucibello, Eugenio Mercuri, Christopher Spurney, Paula Clemens, Lauren Morgenroth, Heather Gordish-Dressman, Craig M McDonald, Eric P Hoffman, Elena Pegoraro
Background: Dilated cardiomyopathy (DCM) is a major complication of, and leading cause of mortality in Duchenne muscular dystrophy (DMD). Its severity, age at onset, and rate of progression display wide variability, whose molecular bases have been scarcely elucidated. Potential DCM-modifying factors include glucocorticoid (GC) and cardiological treatments, DMD mutation type and location, and variants in other genes.
Methods and results: We retrospectively collected 3138 echocardiographic measurements of left ventricular ejection fraction (EF), shortening fraction (SF), and end-diastolic volume (EDV) from 819 DMD participants, 541 from an Italian multicentric cohort and 278 from the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS). Using generalized estimating equation (GEE) models, we estimated the yearly rate of decrease of EF (-0.80%) and SF (-0.41%), while EDV increase was not significantly associated with age. Utilizing a multivariate generalized estimating equation (GEE) model we observed that mutations preserving the expression of the C-terminal Dp71 isoform of dystrophin were correlated with decreased EDV (-11.01 mL/m2, p = 0.03) while for dp116 were correlated with decreased EF (-4.14%, p = <0.001). The rs10880 genotype in the LTBP4 gene, previously shown to prolong ambulation, was also associated with increased EF and decreased EDV (+3.29%, p = 0.002, and -10.62 mL/m2, p = 0.008) with a recessive model.
Conclusions: We quantitatively describe the progression of systolic dysfunction progression in DMD, confirm the effect of distal dystrophin isoform expression on the dystrophin-deficient heart, and identify a strong effect of LTBP4 genotype of DCM in DMD.
背景:扩张型心肌病(DCM)是杜氏肌营养不良症(DMD)的主要并发症和致死原因。其严重程度、发病年龄和进展速度变化很大,其分子基础几乎尚未阐明。潜在的 DCM 改变因素包括糖皮质激素(GC)和心脏病治疗、DMD 基因突变类型和位置以及其他基因的变异:我们回顾性地收集了819名DMD患者的3138例左心室射血分数(EF)、缩短分数(SF)和舒张末期容积(EDV)的超声心动图测量数据,其中541例来自意大利多中心队列,278例来自国际神经肌肉合作组织杜氏自然史研究(CINRG-DNHS)。通过使用广义估计方程(GEE)模型,我们估算出了EF(-0.80%)和SF(-0.41%)的年下降率,而EDV的增加与年龄并无显著关联。利用多变量广义估计方程(GEE)模型,我们观察到,保留肌营养不良蛋白 C 端 Dp71 异构体表达的突变与 EDV 的下降相关(-11.01 mL/m2,p = 0.03),而 dp116 的突变与 EF 的下降相关(-4.14%,p = 结论:我们定量描述了DMD患者收缩功能障碍的发展过程,证实了远端淀粉样蛋白同工酶表达对淀粉样蛋白缺乏心脏的影响,并发现LTBP4基因型对DMD患者的DCM有很大影响。
{"title":"The IAAM LTBP4 Haplotype is Protective Against Dystrophin-Deficient Cardiomyopathy.","authors":"Luca Bello, Daniele Sabbatini, Aurora Fusto, Domenico Gorgoglione, Giovanni Umberto Borin, Martina Penzo, Pietro Riguzzi, Matteo Villa, Sara Vianello, Chiara Calore, Paola Melacini, Riccardo Vio, Andrea Barp, Grazia D'Angelo, Sandra Gandossini, Luisa Politano, Angela Berardinelli, Sonia Messina, Gian Luca Vita, Marina Pedemonte, Claudio Bruno, Emilio Albamonte, Valeria Sansone, Giovanni Baranello, Riccardo Masson, Guja Astrea, Adele D'Amico, Enrico Bertini, Marika Pane, Simona Lucibello, Eugenio Mercuri, Christopher Spurney, Paula Clemens, Lauren Morgenroth, Heather Gordish-Dressman, Craig M McDonald, Eric P Hoffman, Elena Pegoraro","doi":"10.3233/JND-230129","DOIUrl":"10.3233/JND-230129","url":null,"abstract":"<p><strong>Background: </strong>Dilated cardiomyopathy (DCM) is a major complication of, and leading cause of mortality in Duchenne muscular dystrophy (DMD). Its severity, age at onset, and rate of progression display wide variability, whose molecular bases have been scarcely elucidated. Potential DCM-modifying factors include glucocorticoid (GC) and cardiological treatments, DMD mutation type and location, and variants in other genes.</p><p><strong>Methods and results: </strong>We retrospectively collected 3138 echocardiographic measurements of left ventricular ejection fraction (EF), shortening fraction (SF), and end-diastolic volume (EDV) from 819 DMD participants, 541 from an Italian multicentric cohort and 278 from the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS). Using generalized estimating equation (GEE) models, we estimated the yearly rate of decrease of EF (-0.80%) and SF (-0.41%), while EDV increase was not significantly associated with age. Utilizing a multivariate generalized estimating equation (GEE) model we observed that mutations preserving the expression of the C-terminal Dp71 isoform of dystrophin were correlated with decreased EDV (-11.01 mL/m2, p = 0.03) while for dp116 were correlated with decreased EF (-4.14%, p = <0.001). The rs10880 genotype in the LTBP4 gene, previously shown to prolong ambulation, was also associated with increased EF and decreased EDV (+3.29%, p = 0.002, and -10.62 mL/m2, p = 0.008) with a recessive model.</p><p><strong>Conclusions: </strong>We quantitatively describe the progression of systolic dysfunction progression in DMD, confirm the effect of distal dystrophin isoform expression on the dystrophin-deficient heart, and identify a strong effect of LTBP4 genotype of DCM in DMD.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}