The impact of pain and nocturnal cramps on sleep quality in Charcot Marie Tooth disease: a case-control study

Introduction: Charcot-Marie-Tooth disease is an inherited neuropathy that presents two main forms - type 1 and type 2 -, differentiated by the speed of the nervous conduction. Our goal was to assess sleep in Charcot-Marie-Tooth disease and its relationship with pain perception and nocturnal cramps. Material and Methods: This was a case-control study. The case group was composed of 10 volunteers diagnosed with the type 1 and 23 with the type 2. The control group was composed of 22 individuals from the same family matched by age and gender. Volunteers underwent clinical screening to assess the presence of nocturnal cramps and filled the brief pain inventory, the Chalder fatigue scale, the Epworth sleepiness scale, and the Pittsburgh sleep quality index. Sleep was evaluated by actigraphy. Results: Type 2 patients presented a more severe perception of pain and fatigue, more time spend awake after sleep onset, and had lower sleep efficiency. The individuals who reported nocturnal cramps also had worse perception of pain, reduced sleep latency, and increased sleep fragmentation. Conclusion: The Charcot-Marie-Tooth type 2 was related with worse sleep quality, perception of pain, and fatigue and these parameters were negatively related

Analysis of the rhythm of activity and rest and of the melatonin profile in patients with Fabry disease

Introduction: Fabry’s disease is caused by a mutation in GLA gene, whose consequence is the accumulation of glycosphingolipids within the lysosomes. The classic symptomatology of the disease develops in the first decades of life and includes dermatological, neurological, ocular, cardiac and renal manifestations. Non-classical manifestation occurs later in life and is restricted to involvement of heart and kidneys. Besides these symptoms, the patients present behavioral changes in sleep/wake cycle such as excessive daytime sleepiness, sleep-disordered breathing and abnormal periodic leg movements. Sleep propensity is regulated by a homeostatic and a circadian component, that is rhythmic, oscillates with a periodicity of approximately, 24 hours, synchronized by environmental cues, and orchestrated by a biological clock. The clock can be assessed by markers of biological rhythmicity, as the rhythm of activity and rest and variation of body temperature, and by endogenous rhythm of chronobiotics, as melatonin biosynthesis. Behavioral manifestations of sleep/wake cycle in Fabry disease could be related to modifications in the internal temporal order, and, as a consequence, an alteration in melatonin daily profile and, maybe, in orders rhythmic manifestations. Objective: To assess the effect of lysosomal dysfunction in Fabry disease patients on activity, rest and melatonin rhythms. Methods: The investigation followed a case-control design and was approved by Institution's Ethics Committee (Universidade Federal de São Paulo). Sixteen patients with classic variant (11 on enzyme replacement therapy, 10 women) with a mean age of 36.4 ± 3.0 years and seven patients with non-classic variant (4 on enzyme replacement therapy, 6 women) with a mean age 44.0 ± 4.6 year were recruited. Control group was matched by age and gender, consisting on fourteen volunteers (10 women), with mean age of 42.4 ± 3.2 years. The volunteers answered three questionnaires (Epworth Sleepiness Scale, Morningness-eveningness questionnaire and Pittsburgh Sleep Quality Index), activity, rest and peripheral body temperature values were determined for at least ten days by actigraphy. The 6-sulfatoxymelatonin dosage in urine (second urine in the morning until 7 p.m. – Day; 7.p.m. until first urine in the next morning - Night) and melatonin on saliva (7 p.m. to 9:30 p.m.) were also performed. Results: Control group presented 6-sulfatoxymelatonin excretion load higher during the night than day. Fabry disease with non-classic variant group presented higher levels of 6-sulfatoxymelatonin during the day compared with control group, while Fabry disease with classic variant had no oscillatory pattern, which was observed for control group. Also, was found an increase in peripheral body temperature period between Fabry with classic variant and control group. No differences were found between the groups for other parameters evaluated. Conclusion: These results show a rhythm disruption on 6-sulfatoxymelatonin profile in Fabry disease patients, emphasized by differences in excretion load of this metabolite observed in patients.Introdução: A Doença de Fabry é causada por mutação no gene GLA, cuja consequência é o acúmulo de glicoesfingolípidos no interior dos lisossomos. A sintomatologia clássica da doença se desenvolve nas primeiras décadas de vida e abrange manifestações dermatológicas, neurológicas, oculares, cardíacas e renais. Já a manifestação não clássica é mais tardia e se restringe ao comprometimento do coração e dos rins. Além dos sintomas, os pacientes apresentam alterações comportamentais do ciclo sono/vigília, como sonolência diurna excessiva, distúrbios respiratórios do sono e movimento periódico de membros inferiores. A propensão ao sono é regulada por um componente homeostático e um componente circadiano, que é rítmico, oscila com uma periodicidade de aproximadamente 24 horas, sincronizado por pistas ambientais, e é orquestrado pelo sistema de temporização. Esse sistema pode ser avaliado por marcadores de ritmicidade biológica, como o ritmo de atividade e repouso e variação de temperatura corporal, assim como pelo ritmo endógeno de cronobióticos, como a biossíntese de melatonina. As alterações do ciclo sono/vigília observadas nos pacientes diagnosticados com Doença de Fabry podem estar relacionadas com uma modificação da ordem temporal interna e consequente modificação no padrão diário de melatonina, e talvez, na manifestação de outros ritmos. Objetivo: Avaliar o efeito da disfunção lisossômica na Doença de Fabry sobre os ritmos de atividade e repouso e de melatonina. Métodos:. Estudo do tipo caso-controle conduzido na cidade de São Paulo, aprovado pelo Comitê de Ética em Pesquisa da Universidade Federal de São Paulo. Foram recrutados 16 pacientes com variante clássica (11 em terapia de reposição enzimática, 10 mulheres) e 7 pacientes com variante não clássica (4 em terapia de reposição enzimática, 6 mulheres) com média de idade de 36,4 ± 3,0 anos e de 44,0 ± 4,6 anos, respectivamente. O grupo controle foi pareado por gênero e idade, sendo composto por 14 indivíduos (10 mulheres), com média de idade de 42,4 ± 3,2 anos. Foi feita uma avaliação por meio de três questionários (escala de sonolência diurna, identificação de cronotipo de Horne e índice de qualidade de sono), atividade e temperatura corporal periférica foram determinados por no mínimo 10 dias de uso do actígrafo e dosagem de 6-sulfatoximelatonina (segunda urina da manhã até 19:00 – Dia; 19:00 até a primeira urina da manhã do dia seguinte - Noite) e melatonina (19:00 às 21:30), na urina e saliva respectivamente. Resultados: O grupo controle apresentou porcentagem de carga excretada de 6-sulfatoximelatonina maior durante a noite que durante o dia. O grupo Fabry com a variante não clássica apresentou um aumento de excreção deste metabólito durante o dia quando comparado com grupo controle, enquanto no grupo Fabry com a variante clássica a oscilação observada no grupo controle estava ausente. Foi encontrado um aumento de período de temperatura corporal periférica entre o grupo Fabry com a variante clássica e o grupo controle. Não foram encontradas diferenças entre os grupos para os outros parâmetros avaliados. Conclusão: Esses resultados mostram que há uma alteração rítmica no perfil de 6-sulfatoximelatonina na Doença de Fabry, evidenciada pelas modificações de carga excretada deste metabólito observada nos pacientes.Associação Fundo de Incentivo à Pesquisa (AFIP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq: 133727/2016-5Dados abertos - Sucupira - Teses e dissertações (2018

Well-being of college students: effects of a mindfulness-based intervention on sleep and biological rhythms

Estudantes universitários são uma população exposta a condições que prejudicam sua saúde física e mental como a irregularidade nos padrões de sono e exposição inadequada à luz, cujas consequências incluem alta prevalência de sintomas de ansiedade, depressão, alterações de sono e desajuste circadiano. Evidências têm demonstrado que as intervenções baseadas em mindfulness promovem saúde e bem-estar ao desenvolver no praticante habilidades que lhe resguardam de eventos mentais negativos. Alguns trabalhos demonstram que a prática regular também é capaz de melhorar a qualidade de sono e reduzir as queixas associadas a esse comportamento. Dessa forma, o objetivo deste trabalho foi caracterizar o bem-estar subjetivo de estudantes universitários e avaliar os efeitos do Programa de Promoção da Saúde Baseado em Mindfulness sobre o sono e ritmos circadianos, visto que umas das atuações do sistema de temporização é sobre a regulação da propensão ao sono. Essa tese foi dividida em dois estudos: o Estudo 1, transversal, no qual 615 estudantes preencheram um formulário eletrônico que continha questões sobre fatores sociodemográficos e comportamentais que poderiam estar relacionados com o bem-estar subjetivo. Foi aplicado um modelo de mediação para avaliar o efeito dos fatores sociodemográficos sobre variáveis comportamentais mediadoras e sobre o desfecho principal, o bem-estar subjetivo. O Estudo 2, longitudinal, randomizado, controlado, com dois braços paralelos (Programa de Promoção da Saúde Baseado em Mindfulness e Psico-educação em Sono). As intervenções constituíram-se de oito encontros semanais (um por semana), com duração de uma hora, as avaliações foram feitas em três momentos: pré-intervenção (dez dias antes do início da intervenção), durante (entre a terceira e quarta semanas) e pós-intervenção (uma semana após o término da intervenção). As medidas incluíram questionários validados com base no autorrelato sobre a qualidade de sono, estresse, bem-estar e saúde mental, e objetivas, pelo uso da actigrafia e pela quantificação de parâmetros circadianos. No Estudo 1 observamos que alguns fatores estavam associados com maior bem-estar subjetivo: preferências circadianas matutinas, identificação com o gênero masculino, saúde mental preservada e prática de pilates ou yoga. Já as variáveis que mediaram o bem-estar subjetivo foram: estresse percebido, qualidade subjetiva de sono, sintomas de depressão e afetos positivos. Já no Estudo 2 não observamos efeitos significativos do Programa de Promoção da Saúde Baseado em Mindfulness sobre a qualidade subjetiva e objetiva de sono, estimada pela actigrafia, e sobre a ritmicidade circadiana, quando comparados os três momentos de avaliação e com o grupo controle. No entanto, o Programa foi capaz de aumentar o bem-estar subjetivo dos estudantes e, a depender do desfecho, o cronotipo foi moderador de alguns efeitos de ambas as intervenções. Houve uma maior adaptação dos estudantes com tendências vespertinas ao Programa de Promoção da Saúde Baseado em Mindfulness (ex. aumento do bem-estar subjetivo que se manteve no follow-up de seis meses) e a Psico-educação em Sono (ex. aumento do MESOR, avanço do M10c e aumento da razão noite/dia da excreção de 6-sulfatoximelatonina). Nosso objetivo de caracterização do bem-estar subjetivo de estudantes universitários foi contemplado, assim como pudemos descrever os efeitos do Programa de Promoção da Saúde Baseado em Mindfulness sobre o sono e ritmos circadianos.College students are a population exposed to conditions that impair their physical and mental health, such as sleep irregularity and inadequate exposure to light, whose implications include a high prevalence of anxiety symptoms, depression, sleep alterations, and circadian misalignment. Evidence has shown that mindfulness-based interventions promote health and well-being by developing skills that protect the practitioner from negative mental events. Some studies show that regular practice also improves sleep quality and reduces complaints associated with this behavior. Thus, the purpose of this study was to characterize the subjective well-being of college students and evaluate the effects of the Mindfulness-Based Health Promotion Program on sleep and circadian rhythms, since one of the actions of the timing system is the regulation of sleep propensity. This thesis was divided into two studies: Study 1, a cross-sectional one, in which 615 students filled an electronic form containing questions about sociodemographic and behavioral factors that could be related to subjective well-being. A mediation model was applied to assess the effect of sociodemographic factors on mediating behavioral variables and on the primary outcome, subjective well-being. Study 2 was a longitudinal, randomized, controlled trial with two parallel arms (Mindfulness-Based Health Promotion Program and Sleep Psychoeducation). Interventions consisted of eight weekly (one per week), one-hour meetings, and assessments were made at three-time points: pre-intervention (ten days before the start of the intervention), during (between the third and fourth weeks), and post-intervention (one week after the end of the intervention). Measures included validated questionnaires based on self-reports of sleep quality, stress, well-being, and mental health, and objective measures by actigraphy and quantification of secretion of circadian phase markers. In Study 1 we observed that some factors were associated with greater subjective well-being: morning circadian preferences, identification with the male gender, preserved mental health, and practice of pilates or yoga. The variables that mediated subjective well-being were perceived stress, subjective sleep quality, depression symptoms, and positive affect. In Study 2, we did not observe significant effects of the Mindfulness-Based Health Promotion Program on the subjective and objective sleep quality, estimated by actigraphy, and on the circadian markers, between and within groups. However, the Program was effective in increasing students' subjective well-being, and chronotype moderated some effects of both interventions, depending on the outcome. There was a greater adaptation of students with eveningness tendencies to the Mindfulness-Based Health Promotion Program (e.g. increased subjective well-being that persisted at six-month follow-up) and to Sleep Psychoeducation (e.g., increased MESOR, advanced M10c, and increased night/day ratio of 6-sulfatoxymelatonin excretion). We met our initial goal of characterizing the subjective well-being of college students, and we were able to describe the effects of the Mindfulness-Based Health Promotion Program on sleep and circadian rhythms.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)2018/18889-

Effectiveness of digital cognitive-behavioral therapy for insomnia alone or combined with sleep medication: A real-world evidence study

Insomnia is a highly prevalent sleep disorder, but its first line of treatment (Cognitive Behavioral Therapy for Insomnia - CBTi) is not widely available and affordable. Digital therapy has been an alternative to these limitations and its combination with pharmacological treatment may improve patients' clinical outcomes and therapy adherence. This was a real-world evidence study aimed to evaluate the efficacy of a CBTi smartphone app combined or not with sleep medication, based on a sample of users of a CBTi smartphone app (SleepUp®) registered between June 2020 and June 2022. Individuals were categorized into two groups (“dCBTi alone” and “dCBTi combined”) according to their self-reported use of sleep medication on the first day of treatment. Assessments were made based on the self-report of sleep logs (sleep quality and efficiency) and on insomnia severity (Insomnia Severity Index). Comparisons were made considering the first entry (baseline) and the mean of the last three days in which sleep logs were filled out (final). The final samples comprised 143 individuals: 73 (51%) reported using sleep medication at baseline, while 70 (49%) did not. In both groups, there was an improvement in sleep quality, (p<0.001), sleep efficiency (p<0.001), and insomnia severity (p<0.001). The magnitude of effects on sleep efficiency and insomnia severity was greater in the dCTBi combined group. This result indicates that dCBTi can be useful as an adjuvant treatment for insomnia

Effectiveness of a specific physical therapy program for Charcot-Marie-Tooth on sleep quality, pain perception, and nocturnal cramps: a pilot study

Introduction: Chronic pain, nocturnal cramps, and sleep alterations are prevalent symptoms and signals in Charcot-Marie-Tooth disease patients. Sleep and pain are bidirectionally related and physical therapy can improve the binomial sleep and pain/nocturnal cramps. Therefore, we hypothesized that the application of a specific physical therapy program for Charcot-Marie-Tooth disease would improve sleep quality, pain perception, and nocturnal cramps. Material and Methods: A non-randomized controlled study that included 9 Charcot-Marie-Tooth disease patients (intervention group - physical therapy program) and 8 controls (active control group - booklet on sleep hygiene). The intervention lasted 8 weeks, three sessions per week. The effects were evaluated ten days before (baseline) and ten days after the intervention (post). Our primary outcome was sleep quality (subjective and objective, assessed by Pittsburgh sleep quality index and actigraphy, respectively); and secondary outcomes were pain perception (brief pain inventory) and nocturnal cramps (self-report). Results: The program was able to improve the subjective sleep quality (p=0.005) and nocturnal cramps (p0.05) neither on pain perception (p>0.05). Conclusion: Our initial hypothesis was partially corroborated: the improvement in subjective quality of sleep and nocturnal cramps is already beneficial for the health promotion of the volunteers in this study affected by the disease. Our findings may serve as a basis for future research to develop a program focused on the treatment of analgesia, which can improve pain perception and alter the objective quality of sleep