Long term effects of continuous positive airway pressure treatment of obstructive sleep apnea-hypopnea syndrome in multiple sclerosis patients.

BACKGROUND: Obstructive sleep apnea-hypopnea (OSAH) is common in MS patients and is associated with fatigue. We recently published a randomized, controlled trial (RCT) of active vs sham continuous positive airway pressure (CPAP) treatment in MS patients with fatigue, poor sleep quality, and (OSAH) (Mult Scl J 2022;28:82-92). Our aim was to evaluate the long-term effects of CPAP treatment on fatigue (Fatigue Severity Scale, FSS, primary outcome) and other clinical outcomes in MS patients with OSAH. METHODS: Following the RCT, participants were offered treatment with CPAP and participation in an open label study. Patients were re-evaluated with RCT outcome measures at least 6 months after completion of the RCT. RESULTS: Twenty-eight of 34 (82 %) RCT-completers participated in this study a mean of 2.7 years after the RCT. Sixteen (57 %) patients were treated with CPAP (mean use 5.4 ± 1.0 h/night during the 6 months prior to follow-up visit), while the other 12 patients declined CPAP use and received no other OSAH treatments. Baseline clinical characteristics, including MS related disability and sleep outcomes, were not significantly different between CPAP-treated vs non-CPAP treated patients. Patients using CPAP at follow-up (n = 16) demonstrated significant improvements from RCT baseline in FSS (p = 0.005), Fatigue Scale for Motor and Cognitive Functions (p = 0.008, p = 0.012), Pittsburgh Sleep Quality Index (p = 0.016), Center of Epidemiological Studies-Depression Scale (p = 0.05), and Multiple Sclerosis Quality of Life-54 (MSQOL-54) physical and mental component scores (p = 0.012, p = 0.023), but no improvements in Epworth Sleepiness Scale, Pain Visual Analog Scale, or Expanded Disability Status Scale. Patients not using CPAP (n = 12) had no significant improvements in outcome measures. Using a linear mixed model, FSS (p = 0.03), morning fatigue (p = 0.048), and MSQOL-54 physical component score (p = 0.02) improved significantly in CPAP treated patients compared with non-CPAP treated patients from RCT baseline. CONCLUSION: In this post-RCT open label study, long-term CPAP use was associated with improved fatigue (FSS, our primary outcome) and physical quality of life in MS patients with OSAH.

Effect of continuous positive airway pressure treatment of obstructive sleep apnea-hypopnea in multiple sclerosis: A randomized, double-blind, placebo-controlled trial (SAMS-PAP study).

OBJECTIVE: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the Fatigue Severity Scale (FSS, preplanned primary outcome), another fatigue measure, sleep quality, somnolence, pain, disability, and quality of life in multiple sclerosis (MS) patients with obstructive sleep apnea-hypopnea (OSAH). METHODS: In a randomized, double-blind trial (NCT01746342), MS patients with fatigue, poor subjective sleep quality, and OSAH (apnea-hypopnea index of ⩾ 15 events per hour/sleep), but without severe OSAH (apnea-hypopnea index > 30, and 4% oxygen desaturation index > 15 events/hour or severe somnolence), were randomized to fixed CPAP or sham CPAP for 6 months. Outcome assessments were performed at 3 and 6 months. RESULTS: Of 49 randomized patients, 34 completed the protocol. Among completers, FSS did not improve with CPAP compared to sham at 6 months. FSS tended to improve (p = 0.09), and sleepiness (Epworth Sleepiness Scale) improved significantly (p = 0.03) at 3 months with CPAP compared to sham, but there were no other improvements with CPAP at either study evaluation. CONCLUSION: In non-severe OSAH patients, CPAP did not significantly improve the primary outcome of FSS change at 6 months. In secondary analyses, we found a trend to improved FSS, and a significant reduction in somnolence with CPAP at 3 months.

A Microsoft Kinect-Based Point-of-Care Gait Assessment Framework for Multiple Sclerosis Patients.

Gait impairment is a prevalent and important difficulty for patients with multiple sclerosis (MS), a common neurological disorder. An easy to use tool to objectively evaluate gait in MS patients in a clinical setting can assist clinicians to perform an objective assessment. The overall objective of this study is to develop a framework to quantify gait abnormalities in MS patients using the Microsoft Kinect for the Windows sensor; an inexpensive, easy to use, portable camera. Specifically, we aim to evaluate its feasibility for utilization in a clinical setting, assess its reliability, evaluate the validity of gait indices obtained, and evaluate a novel set of gait indices based on the concept of dynamic time warping. In this study, ten ambulatory MS patients, and ten age and sex-matched normal controls were studied at one session in a clinical setting with gait assessment using a Kinect camera. The expanded disability status scale (EDSS) clinical ambulation score was calculated for the MS subjects, and patients completed the Multiple Sclerosis walking scale (MSWS). Based on this study, we established the potential feasibility of using a Microsoft Kinect camera in a clinical setting. Seven out of the eight gait indices obtained using the proposed method were reliable with intraclass correlation coefficients ranging from 0.61 to 0.99. All eight MS gait indices were significantly different from those of the controls (p-values less than 0.05). Finally, seven out of the eight MS gait indices were correlated with the objective and subjective gait measures (Pearson's correlation coefficients greater than 0.40). This study shows that the Kinect camera is an easy to use tool to assess gait in MS patients in a clinical setting.

Feasibility of Lung Volume Recruitment in Early Neuromuscular Weakness: A Comparison Between Amyotrophic Lateral Sclerosis, Myotonic Dystrophy, and Postpolio Syndrome.

BACKGROUND: Lung volume recruitment (LVR) is a cough assistance technique used in persons with neuromuscular disorders (NMDs), most typically in those requiring noninvasive ventilation (NIV). Whether it may be useful in persons with NMDs who have milder respiratory impairment is unknown. OBJECTIVE: To assess the feasibility, impact on quality of life (QOL), and preliminary physiological effects of daily LVR in different categories of persons with NMDs who have an early stage of respiratory impairment. DESIGN: Feasibility study. SETTING: Academic tertiary care center. PARTICIPANTS: Outpatients diagnosed with amyotrophic lateral sclerosis (n = 8), postpolio syndrome (n = 10), and myotonic dystrophy (n = 6) who had restrictive respiratory defects but were not yet using NIV. METHODS: Participants were asked to perform LVR up to 4 times daily and log their LVR use in a diary. Physiological measurements and questionnaires were completed at baseline and after 3 months. MAIN OUTCOME MEASUREMENTS: Compliance with LVR use was assessed, along with QOL and willingness to continue the treatment. Physiological measurements included forced vital capacity (FVC), lung insufflation capacity (LIC), and the LIC minus FVC difference. RESULTS: Of the 24 recruited subjects, 7 with amyotrophic lateral sclerosis, 7 with postpolio syndrome, and 5 with myotonic dystrophy completed the study (n = 19). At baseline, mean values for FVC and spontaneous peak cough flow were 59.9% predicted and 373.1 L/min, respectively. For subjects completing the study, 74% were willing to continue long-term LVR use, and QOL scores were not adversely affected by LVR in any NMD subgroup. The LIC-FVC difference increased from baseline to follow-up by a mean of 0.243 L (P = .006) in all subjects (n = 19), suggesting a possible improvement in respiratory system mechanics. CONCLUSIONS: In patients with NMDs who have early restrictive respiratory defects but do not yet require NIV, regular use of LVR is feasible with no negative impact on QOL over a 3-month period and may have physiological benefits. Further work is needed to determine whether early institution of LVR can improve respiratory system mechanics and help delay ventilatory failure in persons with NMDs.

Brain volume and fatigue in patients with postpoliomyelitis syndrome.

BACKGROUND: Acute paralytic poliomyelitis is associated with encephalitis. Early brain inflammation may produce permanent neuronal injury with brain atrophy, which may result in symptoms such as fatigue. Brain volume has not been assessed in postpoliomyelitis syndrome (PPS). OBJECTIVE: To determine whether brain volume is decreased compared with that in normal controls, and whether brain volume is associated with fatigue in patients with PPS. DESIGN: A cross-sectional study. SETTING: Tertiary university-affiliated hospital postpolio and multiple sclerosis (MS) clinics. PARTICIPANTS: Forty-nine ambulatory patients with PPS, 28 normal controls, and 53 ambulatory patients with MS. METHODS: We studied the brains of all study subjects with magnetic resonance imaging by using a 1.5 T Siemens Sonata machine. The subjects completed the Fatigue Severity Scale. Multivariable linear regression models were computed to evaluate the contribution of PPS and MS compared with controls to explain brain volume. MAIN OUTCOME MEASUREMENTS: Normalized brain volume (NBV) was assessed with the automated program Structured Image Evaluation, using Normalization, of Atrophy method from the acquired magnetic resonance images. This method may miss brainstem atrophy. RESULTS: Technically adequate NBV measurements were available for 42 patients with PPS, 27 controls, and 49 patients with MS. The mean (standard deviation) age was 60.9 ± 7.6 years for patients with PPS, 47.0 ± 14.6 years for controls, and 46.2 ± 9.4 years for patients with MS. In a multivariable model adjusted for age and gender, NBV was not significantly different in patients with PPS compared with that in controls (P = .28). As expected, when using a similar model for patients with MS, NBV was significantly decreased compared with that in controls (P = .006). There was no significant association between NBV and fatigue in subjects with PPS (Spearman ρ = 0.23; P = .19). CONCLUSIONS: No significant whole-brain atrophy was found, and no association of brain volume with fatigue in PPS. Brain atrophy was confirmed in MS. It is possible that brainstem atrophy was not recognized by this study.

Polysomnographic measures of disturbed sleep are associated with reduced quality of life in multiple sclerosis.

BACKGROUND: The relationship of objective sleep parameters with health-related quality of life (HRQoL) in multiple sclerosis (MS) has not been studied. OBJECTIVE: To evaluate the relationship between polysomnographic (PSG) parameters and HRQoL in MS. METHODS: Ambulatory MS patients without a known sleep disorder completed the Short Form (36) Health Survey (SF-36), pain visual analog scale, and two consecutive overnight PSGs. HRQoL was assessed using SF-36 Physical and Mental Component Summary (PCS, MCS) scores. Standard objective PSG measures of sleep quality were determined. The relationship between objective sleep parameters and HRQoL was evaluated with multivariate linear regression, adjusting for age, sex, body mass index, disability, and pain. RESULTS: 62 MS patients were included. PSG measures of sleep disruption including stage changes, awakenings, time in N1 sleep, and apnea-hypopnea and total arousal indices were negatively associated (p<0.05) with MCS scores (lower scores indicating poorer HRQoL). PSG parameters reflective of better sleep quality including total sleep time, sleep efficiency, and time in REM sleep were positively associated with MCS scores. PSG parameters were not significantly associated with PCS scores. CONCLUSIONS: PSG-documented sleep disruption negatively impacts, while better objective sleep quality positively impacts on the mental domain of HRQoL in MS.

Response of postpoliomyelitis patients to bisphosphonate treatment.

OBJECTIVE: To evaluate (1) the rate of change of bone mineral density (BMD) at the hip in postpolio patients treated with bisphosphonates compared with the rate of change in BMD in (a) postpolio patients not treated with bisphosphonates and (b) non-postpolio patients treated with bisphosphonates; and (2) to compare the fracture rate in postpolio patients before and after treatment. DESIGN: Retrospective chart review. SETTING: University-affiliated hospital postpolio clinic and bone metabolism clinic. PARTICIPANTS: Patients with at least 2 BMD assessments. We included 144 postpolio patients and 112 non-postpolio patients. For the fracture analysis, 32 postpolio patients with a history of fractures and treatment with bisphosphonates were included. METHODS: The effect of treatment on BMD in postpolio patients was analyzed with use of a multiple linear regression model and a mixed effects model, with the rate of change in hip BMD and the change in BMD from baseline, respectively, as the dependent variables. The effect of treatment on occurrence of fractures in postpolio patients was analyzed with use of conditional logistic regression and Poisson regression. MAIN OUTCOME MEASURES: BMD measurements at the femoral neck (g/cm²) and occurrence of fractures before and after initiation of treatment. RESULTS: In an adjusted model, postpolio patients treated with bisphosphonates (54/144) had a greater rate of change in BMD (0.031 g/cm²/year; 95% confidence interval 0.010-0.052) compared with nontreated postpolio patients. The effect of treatment in postpolio patients was similar to that in non-postpolio patients. Evidence indicated that treated postpolio patients have a lower risk of fracture after treatment (odds ratio 0.3, P = .046; rate ratio 0.4, P = .183). CONCLUSIONS: In this retrospective study, it was found that treatment with oral bisphosphonates significantly increases BMD at the hip in postpolio patients. The effect of bisphosphonate treatment appears to be similar in postpolio patients compared with a control group without polio. Treatment with bisphosphonates may have a protective effect on fracture risk in this population.

Fatigue in post-poliomyelitis syndrome: association with disease-related, behavioral, and psychosocial factors.

OBJECTIVE: To determine the biopsychosocial correlates of general, physical, and mental fatigue in patients with postpoliomyelitis syndrome (PPS) by assessing the additional contribution of potentially modifiable factors after accounting for important nonmodifiable disease-related factors. It was hypothesized that disease-related, behavioral, and psychosocial factors would contribute in different ways to general, physical, and mental fatigue in PPS and that a portion of fatigue would be determined by potentially modifiable factors. DESIGN: Cross-sectional study. SETTING: A tertiary university-affiliated hospital post-polio clinic. PATIENTS: Fifty-two ambulatory patients with PPS who were not severely depressed were included. ASSESSMENT OF RISK FACTORS: Potential correlates for fatigue included disease-related factors (acute polio weakness, time since acute polio, PPS duration, muscle strength, pain, forced vital capacity, maximum inspiratory pressure, maximum expiratory pressure, body mass index, disability, fibromyalgia), behavioral factors (physical activity, sleep quality), and psychosocial factors (depression, stress, self-efficacy). MAIN OUTCOME MEASUREMENTS: Fatigue was assessed with the Multidimensional Fatigue Inventory (MFI; assesses fatigue on 5 subscales) and the Fatigue Severity Scale (FSS). RESULTS: Multivariate models were computed for MFI General, Physical, and Mental Fatigue. Age-adjusted multivariate models with nonmodifiable factors included the following predictors of (1) MFI General Fatigue: maximum inspiratory pressure, fibromyalgia, muscle strength; (2) MFI Physical Fatigue: maximum expiratory pressure, muscle strength, age, time since acute polio; and (3) MFI Mental Fatigue: none. The following potentially modifiable predictors made an additional contribution to the models: (1) MFI General Fatigue: stress, depression; (2) MFI Physical Fatigue: physical activity, pain; and (3) MFI Mental Fatigue: stress. CONCLUSIONS: PPS fatigue is multidimensional. Different types of fatigue are determined by different variables. Potentially modifiable factors account for a portion of fatigue in PPS.

Elevated serum inflammatory markers in post-poliomyelitis syndrome.

OBJECTIVES: To determine (i) whether serum inflammatory markers TNFalpha, IL-1beta. IL-6, and leptin are increased in post-poliomyelitis syndrome (PPS) compared to healthy controls; and (ii) whether an association exists between elevated inflammatory markers and clinical parameters in PPS. The cause of PPS is unknown, but abnormal inflammatory responses have been implicated in several small studies. METHODS: Serum inflammatory markers were measured (by Luminex) in 51 PPS patients and 26 normal controls. Clinical parameters assessed included disease duration, muscle strength (Medical Research Council sumscore), fatigue (Fatigue Severity Scale and Multidimensional Fatigue Inventory), and pain (visual analog scale scores). RESULTS: In PPS, TNFalpha levels, as well as IL-6 and leptin were significantly increased compared to controls (Wilcoxon rank-sum test, p=0.03 for TNFalpha, p=0.03 for IL-6, p=0.01 for leptin). The elevated TNFalpha levels in PPS were associated with increased pain due to illness (Spearman correlation coefficient r=0.36, 95% C.I. 0.09 to 0.57) and specifically, with muscle pain (r=0.38, 95% C.I. 0.11 to 0.59). There were no correlations between inflammatory markers in PPS and joint pain, muscle strength, fatigue, or disease duration. CONCLUSIONS: Serum TNFalpha, IL-6 and leptin levels are abnormally increased in PPS patients. Elevated TNFalpha levels appear to be specifically associated with increased muscle pain.

Osteoporosis in a postpolio clinic population.

OBJECTIVES: To determine (1) the frequency of osteoporosis at the hip and lumbar spine in a postpolio clinic population and (2) the association of lower-extremity muscle strength and other potential contributing factors to osteoporosis with bone density measured at the hip. DESIGN: Cross-sectional study involving a chart review. SETTING: A university-affiliated hospital postpolio clinic. PARTICIPANTS: Patient charts (N=379) were reviewed; 164 (26%) were included, and 215 (74%) were not included primarily (74%) because of the unavailability of bone density results. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Bone density (in g/cm(2)) and T score were assessed at the femoral neck and lumbar spine. Muscle strength was evaluated by manual muscle testing in 7 bilateral lower-extremity muscles. RESULTS: The occurrence of osteoporosis at the hip and lumbar spine was 20 (32%) of 62 and 6 (10%) of 61 in men, 3 (9%) of 33 and 2 (6%) of 32 in premenopausal women, and 18 (27%) of 67 and 7 (11%) of 65 in postmenopausal women, respectively. In a logistic regression model, the presence of osteoporosis at the hip was significantly associated with strength sum score in the same extremity in which the bone density was performed after adjusting for other important risk factors (age, body mass index, time since polio). CONCLUSIONS: Osteoporosis occurred commonly at the hip in a postpolio clinic population. Hip bone density was associated with muscle strength in the same lower extremity.

Sleep-disordered breathing in fatigued postpoliomyelitis clinic patients.

OBJECTIVE: To determine the frequency, predictive factors, and symptoms predictive of sleep-disordered breathing (SDB) in fatigued postpoliomyelitis clinic patients. DESIGN: Cross-sectional, retrospective chart review. SETTING: University-affiliated hospital postpolio clinic. PARTICIPANTS: Postpolio clinic charts (N=590) were reviewed. Ninety-eight patients were included, and 492 patients were not included, primarily because of the lack of a polysomnogram. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Apnea-Hypopnea Index (AHI) calculated as the total number of sleep-related breathing events/total sleep time. RESULTS: The frequency of SDB defined by an AHI score of 5 or more was 65% and by an AHI score of 10 or more was 50%. Obstructive hypopnea was the predominant form, occurring in 86%. Age, sex, age at acute polio, time since polio, weakness and respiratory difficulties at acute polio, bulbar involvement at acute polio and at evaluation, body mass index, pulmonary function measures, alcohol use, sedative drug use, smoking, fibromyalgia, kyphoscoliosis, and scoliosis and ear-nose-throat surgery were not predictive of SDB (AHI scores > or =5 and > or =10). Snoring was more common in subjects with SDB (AHI score > or =5 and > or =10). Some pulmonary function measures correlated with oxygen saturation during sleep in SDB (AHI scores > or =5). CONCLUSIONS: SDB was very common in fatigued postpoliomyelitis clinic patients referred for sleep evaluation. Obstructive hypopnea was the most frequent type. In this preliminary study, snoring tended to predict SDB.

Post-poliomyelitis syndrome.

Post-poliomyelitis syndrome (PPS) is a common neurological disorder that occurs in a large proportion of individuals who have recovered from paralytic poliomyelitis. The main clinical features are new weakness, muscular fatigability, general fatigue, and pain. The primary criteria necessary for the diagnosis of PPS are a history of paralytic poliomyelitis, partial or complete recovery of neurological function followed by a period of stability (usually several decades), persistent new muscle weakness or abnormal muscle fatigability, and the exclusion of other causes of new symptoms. The cause of PPS remains unclear, but is likely due to a distal degeneration of enlarged post-poliomyelitis motor units. Contributing factors to PPS may be aging (with motor neuron loss), overuse, and disuse. PPS is usually a slowly progressive neuromuscular disease. Although there is no specific treatment for PPS, an interdisciplinary management program can be useful in controlling symptoms.

Effort-limited treadmill walk test: reliability and validity in subjects with postpolio syndrome.

OBJECTIVE: To determine the reliability and construct validity of an effort-limited treadmill walk test to measure functional ability in subjects with postpolio syndrome in an outpatient postpolio clinic. DESIGN: Functioning and distance walked on a treadmill to a Borg "hard" effort level were measured three times, a week apart, by two blinded raters in 15 subjects with postpolio syndrome, aged 37-67 yrs, with new weakness, fatigue, and pain but with no other cause of symptomatology or condition-limiting walking. One rater tested them twice. Fatigue activity level, mobility, and health-related quality of life (Medical Outcome Study Short Form Health Survey [SF-36]) defined functioning. Generalizability correlation coefficients determined intrarater, test-retest and interrater reliability. The correlations relating the distance walked and functioning determined construct validity. RESULTS: Reliability for generalizability correlation coefficients were: intrarater, 0.91; test-retest, 0.85; and interrater, 0.58. Interrater reliability improved to 0.91 with adherence to a standardized protocol. Validity was established with correlations between the distance walked and SF-36 physical component score (0.66), physical role (0.60), bodily pain (0.60), and vitality (0.55). CONCLUSIONS: The treadmill walk test provides a reproducible and valid measure of ability in persons with postpolio syndrome with a single rater, but a standardized protocol is essential for reliability.

Predictive factors and correlates for pain in postpoliomyelitis syndrome patients.

OBJECTIVE: To identify predictive and associated factors for muscle and joint pain in postpoliomyelitis syndrome (PPS). DESIGN: Cross-sectional study design. SETTING: Postpolio clinics. PARTICIPANTS: Baseline data on 126 PPS patients entered into a multicentered clinical trial. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Adjusted odds ratios were computed by using logistic regression modeling. Patients with or without muscle or joint pain were compared with regard to predictors and associated factors. RESULTS: In multivariate analyses for muscle pain, significant predictive and associated factors were female gender (P=.0006), longer duration of general fatigue (P=.019), and a lower score on the general health scale (P=.009) of the Medical Outcomes Study 36-Item Short-From Health Survey (SF-36). In multivariate analyses for joint pain, significant predictive and associated factors were female gender (P<.003), longer latency (duration of stability after polio; P=.008), younger age at interview (P<.002), greater weakness at acute polio (P<.07), weaker lower-extremity muscle strength (P<.04), and a lower SF-36 general health scale score (P<.02). CONCLUSIONS: Women are more likely to report muscle and joint pain in PPS. Greater initial motor unit involvement and lower-extremity weakness may be additional important factors for determining joint pain. Both muscle and joint pain are associated with reductions in quality of life.