Longitudinal assessment of clinical and inflammatory markers in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate potential associations between clinical features and inflammatory markers in patients with amyotrophic lateral sclerosis (ALS). METHODS: A consecutive series of 68 patients (39 males and 29 females) with sporadic ALS were subjected to a comprehensive clinical assessment and blood draw. A subset of these patients underwent a new assessment within 6-12 months after the baseline visit. In addition, a group of 62 subjects composed by age and sex-matched healthy subjects (38 males and 24 females) was enrolled in this study. Peripheral blood was drawn and plasma levels of chemokines and cytokines were measured by cytometric bead array and enzyme-linked immunosorbent assay. RESULTS: Our sample was composed by patients with ALS with an average age of 58 (±12.3) years old and 3 (±2.7) years of disease length at the baseline visit. Patients with ALS presented increased plasma levels of interleukin (IL)-6 and IL-8 in comparison with controls. After multivariate analysis, higher levels of IL-6 and lower levels of IL-2 were significantly associated with increased likelihood of ALS diagnosis. When evaluating the subset of patients assessed longitudinally, we did not find any significant difference in the levels of inflammatory markers between the two time points. Older age at ALS onset was the only factor associated with a faster rate of disease progression. CONCLUSIONS: IL-6 levels could discriminate between ALS and controls and may be regarded as a potential biomarker of ALS diagnosis. An increase in IL-2 levels was associated with a protective effect on the odds of ALS diagnosis. Older age at ALS onset predicted a fast rate of disease progression.

Depression and anxiety in a case series of amyotrophic lateral sclerosis: frequency and association with clinical features.

Objective: To investigate the frequency of anxiety and depression and their association with clinical features of amyotrophic lateral sclerosis. Methods: This is a cross-sectional and descriptive study including a consecutive series of patients with sporadic amyotrophic lateral sclerosis according to Awaji's criteria. Patients underwent clinical and psychiatric assessment (anxiety and depression symptoms). Results: We included 76 patients. The men/women ratio was 1.6:1. Participants' mean age at disease onset was 55 years (SD±12.1). Sixty-six patients (86.8%) were able to complete psychiatric evaluation. Clinically significant anxiety was found in 23 patients (34.8%) while clinically significant depression was found in 24 patients (36.4%). When we compared patients with and without depression a significant difference was seen only in the frequency of anxiety symptoms (p<0.001). We did further analysis comparing subgroups of patients classified according to the presence or not of anxiety and or depression, without any significant difference regarding sex, age at onset, initial form, disease duration or functional measures. A positive correlation between anxiety and depressive symptoms was found (p<0.001). Conclusion: Anxiety and depressive symptoms were highly correlated and frequent in patients with amyotrophic lateral sclerosis. In addition, anxiety and depression were not associated with disease duration and presentation, sex, age at onset, and functional score. Objetivo: Investigar a frequência de ansiedade e depressão e sua associação com aspectos clínicos da esclerose lateral amiotrófica. Métodos: Estudo transversal e descritivo de uma série consecutiva de pacientes com esclerose lateral amiotrófica esporádica conforme os critérios de Awaji. Os pacientes foram submetidos à avaliação clínica e psiquiátrica (sintomas depressivos e ansiosos). Resultados: Foram incluídos 76 pacientes. A relação homem/mulher foi de 1,6:1. A média de idade de início dos sintomas foi de 55 anos (DP±12,1). Foram capazes de completar a avaliação psiquiátrica 66 (86,8%) pacientes. Ansiedade clinicamente significativa foi encontrada em 23 pacientes (34,8%), enquanto depressão clinicamente significativa foi encontrada em 24 pacientes (36,4%). Ao comparar os pacientes com e sem depressão, houve diferença significativa apenas na frequência de sintomas de ansiedade (p<0,001). Posteriormente, foram comparados subgrupos de pacientes categorizados em relação à presença ou não de ansiedade e/ou depressão, sem diferença significativa em relação a sexo, idade de início dos sintomas, forma inicial, duração da doença ou na escala funcional. Foi encontrada correlação positiva entre os sintomas de ansiedade e depressão (p<0,001). Conclusão: Sintomas de ansiedade e depressão são frequentes em pacientes com esclerose lateral amiotrófica e estiveram altamente correlacionados. Ansiedade e depressão não foram associadas com duração da doença, forma inicial, sexo, idade de início dos sintomas e pontuação na escala funcional.

Effects of non-invasive ventilation and posture on chest wall volumes and motion in patients with amyotrophic lateral sclerosis: a case series.

BACKGROUND: The effects of non-invasive ventilation (NIV) on the breathing pattern and thoracoabdominal motion of patients with amyotrophic lateral sclerosis (ALS) are unknown. OBJECTIVES: 1) To analyze the influence of NIV on chest wall volumes and motion assessed by optoelectronic plethysmography in ALS patients and 2) to compare these parameters in the supine and sitting positions to those of healthy individuals (without NIV). METHOD: Nine ALS patients were evaluated in the supine position using NIV. In addition, the ALS patients and nine healthy individuals were evaluated in both sitting and supine positions. Statistical analysis was performed using the paired Student t-test or Wilcoxon test and the Student t-test for independent samples or Mann-Whitney U test. RESULTS: Chest wall volume increased significantly with NIV, mean volume=0.43 (SD=0.16)L versus 0.57 (SD=0.19)L (p=0.04). No significant changes were observed for the pulmonary rib cage, abdominal rib cage, or abdominal contribution. The index of the shortening velocity of the diaphragmatic muscle, mean=0.15 (SD=0.05)L/s versus 0.21 (SD=0.05)L/s (p<0.01), and abdominal muscles, mean=0.09 (SD=0.02)L/s versus 0.14 (SD=0.06)L/s (p<0.01), increased during NIV. Comparisons between the supine and sitting positions showed similar changes in chest wall motion in both groups. However, the ALS patients presented a significantly lower contribution of the abdomen in the supine position compared with the controls, mean=56 (SD=13) versus 69 (SD=10) (p=0.02). CONCLUSIONS: NIV improved chest wall volumes without changing the contribution of the chest wall compartment in ALS patients. In the supine position, ALS patients had a lower contribution of the abdomen, which may indicate early diaphragmatic dysfunction.

Amyotrophic lateral sclerosis in Brazil: Case series and review of the Brazilian literature.

Our objective was to systematically analyse the first series of cases of amyotrophic lateral sclerosis (ALS) in Minas Gerais and to review the Brazilian literature about clinical studies in ALS. This was a cross-sectional and descriptive study of a consecutive series of patients with probable or defined sporadic ALS according to the Awaji criteria, followed at two referral centres of Belo Horizonte (South-east Brazil). Patients underwent full clinical assessment. Comparisons of patient subgroups according to disease duration and initial presentation were performed. A systematic review was performed about Brazilian clinical studies in ALS. Results showed that of the 61 enrolled patients the male/female ratio was 1.6:1. The mean age at onset of symptoms was 54.9 years (SD ± 11.4). Mean age at diagnosis was 56.3 years (SD ± 11.1). Regarding the initial form of presentation, 43 cases (70.5%) were spinal, 12 cases (19.7%) were generalized and six cases (9.8%) were bulbar. Eight studies were found in the systematic review. In conclusion, the profile of our sample was similar to other national and international series, except for fewer cases of bulbar ALS in our series. There are few clinical studies of ALS in Brazil. The national data of prevalence and incidence are still uncertain.

Depression and anxiety in a case series of amyotrophic lateral sclerosis: frequency and association with clinical features / Depressão e ansiedade em uma série de casos de esclerose lateral amiotrófica: frequência e associação com aspectos clínicos

ABSTRACT Objective To investigate the frequency of anxiety and depression and their association with clinical features of amyotrophic lateral sclerosis. Methods This is a cross-sectional and descriptive study including a consecutive series of patients with sporadic amyotrophic lateral sclerosis according to Awaji’s criteria. Patients underwent clinical and psychiatric assessment (anxiety and depression symptoms). Results We included 76 patients. The men/women ratio was 1.6:1. Participants’ mean age at disease onset was 55 years (SD±12.1). Sixty-six patients (86.8%) were able to complete psychiatric evaluation. Clinically significant anxiety was found in 23 patients (34.8%) while clinically significant depression was found in 24 patients (36.4%). When we compared patients with and without depression a significant difference was seen only in the frequency of anxiety symptoms (p<0.001). We did further analysis comparing subgroups of patients classified according to the presence or not of anxiety and or depression, without any significant difference regarding sex, age at onset, initial form, disease duration or functional measures. A positive correlation between anxiety and depressive symptoms was found (p<0.001). Conclusion Anxiety and depressive symptoms were highly correlated and frequent in patients with amyotrophic lateral sclerosis. In addition, anxiety and depression were not associated with disease duration and presentation, sex, age at onset, and functional score.

RESUMO Objetivo Investigar a frequência de ansiedade e depressão e sua associação com aspectos clínicos da esclerose lateral amiotrófica. Métodos Estudo transversal e descritivo de uma série consecutiva de pacientes com esclerose lateral amiotrófica esporádica conforme os critérios de Awaji. Os pacientes foram submetidos à avaliação clínica e psiquiátrica (sintomas depressivos e ansiosos). Resultados Foram incluídos 76 pacientes. A relação homem/mulher foi de 1,6:1. A média de idade de início dos sintomas foi de 55 anos (DP±12,1). Foram capazes de completar a avaliação psiquiátrica 66 (86,8%) pacientes. Ansiedade clinicamente significativa foi encontrada em 23 pacientes (34,8%), enquanto depressão clinicamente significativa foi encontrada em 24 pacientes (36,4%). Ao comparar os pacientes com e sem depressão, houve diferença significativa apenas na frequência de sintomas de ansiedade (p<0,001). Posteriormente, foram comparados subgrupos de pacientes categorizados em relação à presença ou não de ansiedade e/ou depressão, sem diferença significativa em relação a sexo, idade de início dos sintomas, forma inicial, duração da doença ou na escala funcional. Foi encontrada correlação positiva entre os sintomas de ansiedade e depressão (p<0,001). Conclusão Sintomas de ansiedade e depressão são frequentes em pacientes com esclerose lateral amiotrófica e estiveram altamente correlacionados. Ansiedade e depressão não foram associadas com duração da doença, forma inicial, sexo, idade de início dos sintomas e pontuação na escala funcional.

Effects of non-invasive ventilation and posture on chest wall volumes and motion in patients with amyotrophic lateral sclerosis: a case series

ABSTRACT Background The effects of non-invasive ventilation (NIV) on the breathing pattern and thoracoabdominal motion of patients with amyotrophic lateral sclerosis (ALS) are unknown. Objectives 1) To analyze the influence of NIV on chest wall volumes and motion assessed by optoelectronic plethysmography in ALS patients and 2) to compare these parameters in the supine and sitting positions to those of healthy individuals (without NIV). Method Nine ALS patients were evaluated in the supine position using NIV. In addition, the ALS patients and nine healthy individuals were evaluated in both sitting and supine positions. Statistical analysis was performed using the paired Student t-test or Wilcoxon test and the Student t-test for independent samples or Mann-Whitney U test. Results Chest wall volume increased significantly with NIV, mean volume=0.43 (SD=0.16)L versus 0.57 (SD=0.19)L (p=0.04). No significant changes were observed for the pulmonary rib cage, abdominal rib cage, or abdominal contribution. The index of the shortening velocity of the diaphragmatic muscle, mean=0.15 (SD=0.05)L/s versus 0.21 (SD=0.05)L/s (p<0.01), and abdominal muscles, mean=0.09 (SD=0.02)L/s versus 0.14 (SD=0.06)L/s (p<0.01), increased during NIV. Comparisons between the supine and sitting positions showed similar changes in chest wall motion in both groups. However, the ALS patients presented a significantly lower contribution of the abdomen in the supine position compared with the controls, mean=56 (SD=13) versus 69 (SD=10) (p=0.02). Conclusions NIV improved chest wall volumes without changing the contribution of the chest wall compartment in ALS patients. In the supine position, ALS patients had a lower contribution of the abdomen, which may indicate early diaphragmatic dysfunction.

Lung inflation by glossopharyngeal breathing and "air stacking" in Duchenne muscular dystrophy.

OBJECTIVE: To compare the use of glossopharyngeal breathing (GPB) and air stacking to increase lung volumes and cough peak flows (CPF), and GPB to increase ventilator-free breathing ability (VFBA), for patients with Duchenne muscular dystrophy. DESIGN: A case series of all referred patients with declining vital capacity (VC). Seventy-eight patients underwent training in and monitoring of the efficacy of air stacking (retaining consecutively delivered volumes of air delivered via manual resuscitator and held by glottic closure) to maximum insufflation capacity (MIC). GPB also was demonstrated to all 78 patients, and 32 were formally trained and prescribed GPB as their VCs decreased below 400 ml. To be successful, the MIC or GPB maximum single-breath capacity (GPmaxSBC) had to exceed VC. Improvements in VFBA were determined by requiring fewer ventilator-assisted breaths per minute. CPFs were measured by peak flow meter. RESULTS: Seventy-four (94.9%) of the patients could air stack (MIC > VC), and, thus far, 21 (27%) are able to GPB. Fifteen could GPB sufficiently to delay onset of daytime ventilator use and, later, to require 1.9 fewer ventilator assisted breaths per minute. For the 47 patients with multiple data points, as VC deteriorated from 1080 +/- 870 to 1001 +/- 785 ml, MIC increased from 1592 +/- 887 to 1838 +/- 774 ml. For 21 patients, GPmaxSBC significantly exceeded VC (824 +/- 584 vs. 244 +/- 151 ml, respectively, P < 0.001). The ability to increase lung volume by air stacking (MIC) was better retained than was the ability to increase lung volume by GPB (GPmaxSBC). Air stacking also permitted assisted CPF to exceed unassisted CPF: 289 +/- 91 and 164 +/- 76 liters/m, respectively (P < 0.001). CONCLUSIONS: GPB and air stacking can increase lung volumes and, thereby, cough flows. GPB also can be used in many cases to delay and decrease daytime ventilator use.