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O sono em doentes com miopatia distal por mutação MATR3: estudo observacional unicêntrico na mutação patogénica p.S85C
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As doenças neuromusculares estão frequentemente associadas a alterações respiratórias do sono, sobretudo quando existe envolvimento diafragmático ou bulbar. A distrofia muscular por variante patogénica p.S85C no gene MATR3 tem sido descrita em diferentes contextos clínicos, mas a caracterização do sono e respiratória nos doentes com
esta variante permanece pouco explorada. Este trabalho teve como objetivo principal caracterizar o sono e o padrão ventilatório noturno em doentes com mutação patogénica p.S85C no MATR3.
Para tal realizou-se um estudo observacional, transversal, do tipo descritivo e correlacional, unicentro, em nove doentes pertencentes a três famílias (66.7% do sexo feminino; idade média 58.78 ± 6.73 anos) com mutação patogénica p.S85C no MATR3, confirmada geneticamente, seguidos em consulta multidisciplinar de Doenças Neuromusculares. A avaliação integrou polissonografia de nível II com capnografia transcutânea, provas funcionais respiratórias, gasometria arterial, extração de parâmetros de ventilação não invasiva (VNI) do dispositivo domiciliário e questionários validados de sono e de qualidade de vida.
Os resultados evidenciaram tendência para um padrão ventilatório restritivo, com 44.4% dos doentes com capacidade vital forçada (CVF) <60% e queda postural da CVF ≥15%
em 66.7% da amostra. Verificou-se diminuição da pressão inspiratória máxima em todos os doentes e da pressão expiratória máxima em 88.9%. O pico de tosse foi ≤270 L/min em 55.5% dos doentes. Na avaliação objetiva do sono observou-se uma mediana de 79% na eficiência, um aumento do tempo de vigília após o início do sono (mediana 91 minutos), redução da percentagem do sono REM (mediana de 13%) e mediana de 2.4/ h do índice de distúrbios respiratórios (IDR). Entre os 7 doentes ventilados, verificou-se uma elevada adesão à VNI (100%) e um baixo índice de apneia-hipopneia residual (0.2/ h). Na avaliação subjetiva, 88.9% dos doentes apresentaram má qualidade de sono no Índice de Pittsburgh (mediana 9) e um perfil de insónia maioritariamente subclínica a moderada em 55.6% dos doentes, com impacto variável na qualidade de vida. A dor e a ansiedade demonstraram associações clinicamente consistentes com a qualidade do sono. Pontuações mais baixas no domínio Dor do SF-36v2 (mais dor) correlacionaram-se com pior qualidade subjetiva e global do sono pelo Índice de Pittsburgh. Por sua vez, níveis mais elevados na subescala Ansiedade do questionário de Insuficiência Respiratória Grave foram associados a pior qualidade do sono no Índice de Pittsburgh (menor duração percebida, menor eficiência e pior qualidade) e maior latência ao sono na polissonografia.
Este é o primeiro estudo a realizar uma caracterização integrada do sono, função respiratória e padrão de utilização de suporte ventilatório em doentes com mutação
patogénica p.S85C no MATR3. Verificou-se que esta patologia neuromuscular se associa a alterações respiratórias relevantes e a perturbações significativas do sono, com implicações para a vigilância clínica. Estes achados reforçam a necessidade de reavaliação periódica da função respiratória e do sono, bem como de intervenções dirigidas a comorbilidades como insónia, ansiedade e dor, para maximizar o beneficio da ventilação não invasiva e melhorar a qualidade de vida destes doentes.
Neuromuscular diseases are frequently associated with sleep-related breathing disorders, especially when there is diaphragmatic or bulbar impairment. The muscular dystrophy due to pathogenic p.S85C variant in the MATR3 gene has been described in different clinical contexts, however sleep and respiratory characterization in patients with this variant remains underexplored. The primary objective of this study aimed to characterize sleep and nocturnal ventilatory patierns in patients with the pathogenic p.S85C mutation in MATR3. To this purpose, a single-center, observational, cross-sectional, descriptive and correlational study was conducted in nine patients from three families (66.7% female; mean age 58.78 ± 6.73 years) with genetically confirmed p.S85C MATR3 mutation, followed in a multidisciplinary Neuromuscular Diseases outpatient care. The assessment included level II polysomnography with transcutaneous capnography, pulmonary function tests, arterial blood gas analysis, extraction of non-invasive ventilation (NIV) parameters from the home device, and validated sleep and health-related quality-of-life questionnaires. Results showed a trend toward a restrictive ventilation patiern, with 44.4% of patients having a forced vital capacity (FVC) < 60% and a postural FVC drop ≥ 15% in 66.7% of the sample. All patients had reduced maximal inspiratory pressure and 88.9% had reduced maximal expiratory pressure. Peak cough flow was ≤ 270 L/min in 55.5% of patients. The objective sleep assessment revealed median sleep efficiency of 79%, increased awakening after sleep onset (median 91 minutes), reduced REM sleep (median 13%) and the median respiratory disturbance index (RDI) was 2.4 events per hour. Among the seven ventilated patients, adherence to NIV was high (100%) and residual apnoea–hypopnea index was low (0.2/ h). Subjectively, 88.9% patients reported poor sleep quality in Pittsburgh Sleep Quality Index (median 9) and a profile of insomnia ranging mostly from subclinical to moderate in 55.6% of patients, with variable impact on quality of life. Pain and anxiety showed clinically consistent associations with sleep quality. Lower scores on the SF-36v2 Pain domain (more pain) correlated with worse subjective and overall sleep quality on the Pittsburgh Sleep Quality Index (PSQI). In turn, higher levels in Severe Respiratory Insufficiency Anxiety subscale were associated with worse sleep on the PSQI (shorter perceived duration, lower efficiency, and poorer quality) and longer latency sleep latency on polysomnography. This is the first study to provide an integrated characterization of sleep, respiratory function, and use of ventilatory support in patients with the pathogenic MATR3 p.S85C mutation. We found that this neuromuscular condition is associated with relevant respiratory alterations and significant sleep disturbances, with implications for clinical surveillance. The findings support the need for periodic re-evaluation of respiratory function and sleep, as well as targeted interventions for comorbidities such as insomnia, anxiety, and pain, to maximize the benefits of NIV and improve patents’ quality of life.
Neuromuscular diseases are frequently associated with sleep-related breathing disorders, especially when there is diaphragmatic or bulbar impairment. The muscular dystrophy due to pathogenic p.S85C variant in the MATR3 gene has been described in different clinical contexts, however sleep and respiratory characterization in patients with this variant remains underexplored. The primary objective of this study aimed to characterize sleep and nocturnal ventilatory patierns in patients with the pathogenic p.S85C mutation in MATR3. To this purpose, a single-center, observational, cross-sectional, descriptive and correlational study was conducted in nine patients from three families (66.7% female; mean age 58.78 ± 6.73 years) with genetically confirmed p.S85C MATR3 mutation, followed in a multidisciplinary Neuromuscular Diseases outpatient care. The assessment included level II polysomnography with transcutaneous capnography, pulmonary function tests, arterial blood gas analysis, extraction of non-invasive ventilation (NIV) parameters from the home device, and validated sleep and health-related quality-of-life questionnaires. Results showed a trend toward a restrictive ventilation patiern, with 44.4% of patients having a forced vital capacity (FVC) < 60% and a postural FVC drop ≥ 15% in 66.7% of the sample. All patients had reduced maximal inspiratory pressure and 88.9% had reduced maximal expiratory pressure. Peak cough flow was ≤ 270 L/min in 55.5% of patients. The objective sleep assessment revealed median sleep efficiency of 79%, increased awakening after sleep onset (median 91 minutes), reduced REM sleep (median 13%) and the median respiratory disturbance index (RDI) was 2.4 events per hour. Among the seven ventilated patients, adherence to NIV was high (100%) and residual apnoea–hypopnea index was low (0.2/ h). Subjectively, 88.9% patients reported poor sleep quality in Pittsburgh Sleep Quality Index (median 9) and a profile of insomnia ranging mostly from subclinical to moderate in 55.6% of patients, with variable impact on quality of life. Pain and anxiety showed clinically consistent associations with sleep quality. Lower scores on the SF-36v2 Pain domain (more pain) correlated with worse subjective and overall sleep quality on the Pittsburgh Sleep Quality Index (PSQI). In turn, higher levels in Severe Respiratory Insufficiency Anxiety subscale were associated with worse sleep on the PSQI (shorter perceived duration, lower efficiency, and poorer quality) and longer latency sleep latency on polysomnography. This is the first study to provide an integrated characterization of sleep, respiratory function, and use of ventilatory support in patients with the pathogenic MATR3 p.S85C mutation. We found that this neuromuscular condition is associated with relevant respiratory alterations and significant sleep disturbances, with implications for clinical surveillance. The findings support the need for periodic re-evaluation of respiratory function and sleep, as well as targeted interventions for comorbidities such as insomnia, anxiety, and pain, to maximize the benefits of NIV and improve patents’ quality of life.
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Palavras-chave
Matrin 3 função pulmonar qualidade do sono polissonografia ventilação não invasiva pulmonary function sleep quality polysomnography noninvasive ventilation