High doses of opioids usage for amyotrophic lateral sclerosis patients with non-invasive ventilation.

INTRODUCTION: While opioids have been found to be useful in relieving suffering in amyotrophic lateral sclerosis (ALS), there is a lack of evidence concerning how and how much to use them in practice. This study was conducted to clarify how opioids were used for patients with ALS. METHODS: We performed a retrospective case-based analysis at a single tertiary neurology center in Tokyo from 2010 to 2018. We enrolled patients with ALS who had died before the end of 2018. We examined the opioid dosage equivalent of morphine hydrochloride and patients' clinical backgrounds, focusing on ventilatory support. RESULTS: Morphine was administered in 110 patients with ALS, and 84 were followed up until their death. Of these 84 patients, 57 (69.9%) did not use mechanical ventilation until death (no-MV group), and 21 (22.9%) utilized only non-invasive ventilation (NIV group). Final morphine dosage in the NIV group was significantly higher (mean 65.7 mg [SD 54.6], range 10-200 mg) than in the no-MV group (mean 31.7 mg [SD 26.9], range 0-120 mg; p = 0.015, Welch's t-test). The NIV group needed psychotropic drugs more frequently than the no-MV group (62% [n = 13] vs. 35% [n = 20]). CONCLUSION: Patients in the NIV group used opioids for a statistically significantly longer time and at a higher dose than those in the no-MV group. Symptom control with opioids alone may be difficult, and the development of multifaceted evaluation and care is desirable.

Cybernic treatment with wearable cyborg Hybrid Assistive Limb (HAL) improves ambulatory function in patients with slowly progressive rare neuromuscular diseases: a multicentre, randomised, controlled crossover trial for efficacy and safety (NCY-3001).

BACKGROUND: Rare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation. Thus far, no therapeutic approaches have been successful in recovering the ambulatory ability. Thus, the aim of this trial was to evaluate the efficacy and safety of cybernic treatment with a wearable cyborg Hybrid Assistive Limb (HAL, Lower Limb Type) in improving the ambulatory function in those patients. RESULTS: We conducted an open-label, randomised, controlled crossover trial to test HAL at nine hospitals between March 6, 2013 and August 8, 2014. Eligible patients were older than 18 years and had a diagnosis of neuromuscular disease as specified above. They were unable to walk for 10 m independently and had neither respiratory failure nor rapid deterioration in gait. The primary endpoint was the distance passed during a two-minute walk test (2MWT). The secondary endpoints were walking speed, cadence, and step length during the 10-m walk test (10MWT), muscle strength by manual muscle testing (MMT), and a series of functional measures. Adverse events and failures/problems/errors with HAL were also evaluated. Thirty patients were randomly assigned to groups A or B, with each group of 15 receiving both treatments in a crossover design. The efficacy of a 40-min walking program performed nine times was compared between HAL plus a hoist and a hoist only. The final analysis included 13 and 11 patients in groups A and B, respectively. Cybernic treatment with HAL resulted in a 10.066% significantly improved distance in 2MWT (95% confidence interval, 0.667-19.464; p = 0.0369) compared with the hoist only treatment. Among the secondary endpoints, the total scores of MMT and cadence at 10MWT were the only ones that showed significant improvement. The only adverse effects were slight to mild myalgia, back pain, and contact skin troubles, which were easily remedied. CONCLUSIONS: HAL is a new treatment device for walking exercise, proven to be more effective than the conventional method in patients with incurable neuromuscular diseases. TRIAL REGISTRATION: JMACTR, JMA-IIA00156.

[A proposal of a novel palliative care scale and analysis of suffering in amyotrophic lateral sclerosis].

OBJECTIVE: We proposed a novel palliative care scale (Amyotrophic Lateral Sclerosis Palliative Care Scale: ALSPCS) for patients with ALS, and analyzed the suffering reported by patients. METHODS: Thirty-one patients participated in the study. The ALSPCS has 15 items to evaluate physical and psychological suffering; patients scored their subjective suffering on a scale of 0-5 for each item. This study analyzed 13 of 15 items. RESULTS: The mean scores obtained from the patients were as follows: 'dyspnea', 2.5; 'pain', 2.4; 'restlessness', 2.4; 'thirst', 3.0; 'burning sensation', 2.0; 'choking', 2.0; 'nausea', 0.4; 'constipation', 1.5; 'insomnia', 2.5; 'anxiety', 3.5; 'loneliness', 2.4; 'irritation', 2.1; and 'communication difficulty', 2.3. Multiple correlation analysis using Spearman's rank correlation coefficient showed significant correlations of dyspnea with restlessness, thirst, burning sensation and anxiety; of restlessness with dyspnea, thirst, loneliness and irritation; and of anxiety with dyspnea, thirst and loneliness (P < 0.0038 after Bonferroni's correction). In the principal component analysis, every item showed a positive loading value in the first principal component. Dyspnea, restlessness, thirst, anxiety, loneliness and irritation had loading values >0.7; thus, these symptoms might be the main features in ALS patients. The total scores or each ALSPCS score showed no significant association with post-assessment survival period. CONCLUSION: This study, using ALSPCS, showed that the subjective suffering of ALS patients was variable and strongly correlated with each other. Appropriate and comprehensive assessment of physical and psychological affliction with ALSPCS could be potentially useful in verifying the effectiveness of palliative care for end-of-life stage ALS patients in the future.

Lung Insufflation Capacity with a New Device in Amyotrophic Lateral Sclerosis: Measurement of the Lung Volume Recruitment in Respiratory Therapy.

OBJECTIVE: The aim of this study was to validate the usefulness of the measurement of lung insufflation capacity (LIC) using the LIC TRAINER (LT) in patients with amyotrophic lateral sclerosis (ALS). METHODS: This retrospective study was conducted in the rehabilitation departments of the Japanese National Center of Neurology and Psychiatry and involved 20 ALS patients who underwent respiratory therapy between April 1, 2014, and December 2017. The vital capacity (VC), maximum insufflation capacity (MIC), and LIC measurements at the start of respiratory therapy were extracted from the medical records, and patients were divided into three groups: group A, VC could not be measured; group B, VC could be measured, but MIC was less than VC; and group C, MIC was larger than VC. LIC could be measured in all groups. In group C, paired t-tests were used to analyze whether there was a significant difference in the volumes measured using different methods. RESULTS: LIC was 950, 1863±595, and 2980±1176 ml in groups A (n=1), B (n=10), and C (n=9), respectively. In groups A and B, LIC could be measured in all patients, even when VC or MIC could not be measured. In group C, the measured LIC value was significantly greater than MIC (p=0.003). CONCLUSION: LIC could be successfully measured using the LT. By using the LT, it was feasible to conveniently perform LIC measurements, suggesting that it could be a useful device for performing respiratory therapy in ALS patients.

Cancer rehabilitation: a barometer for survival?

PURPOSE: This pilot study was conducted to describe the clinical features and functional outcomes of patients attending inpatient rehabilitation for cancer-related deconditioning and neurological deficits and to explore factors associated with improved survival. METHODS: Using a retrospective audit, demographic characteristics, discharge outcomes, survival time, and functional status as measured by Functional Independence Measure (FIM) were recorded for 73 patients. Clinical status was estimated by Karnofsky Performance Status Scale (KPS). Cox regression was used to assess factors associated with improved survival following discharge from rehabilitation. RESULTS: Significant functional gains following rehabilitation were observed in total FIM (p = 0.02), motor FIM (p = 0.001), and KPS (p = 0.003). Length of survival ranged from 9.0 to 25.0 months, with 26 cases surviving to the end of study (censored). Patients scoring a total FIM of ≥80 survived significantly longer than patients scoring <80 (p = 0.002). At discharge, motor FIM scores (p = 0.004), FIM Efficiency (p = 0.001), KPS scores (p = 0.022), ambulation ability (p = 0.026), return to home (p = 0.009), and receipt of in-home services (p = 0.045) were significantly associated with improved survival. CONCLUSIONS: Functional improvement achieved through inpatient rehabilitation was associated with prolonged survival among cancer patients. Rehabilitation leading to improved independence among cancer patients may act as a marker of those with greater likelihood of better prognosis.

Evaluation of diffusional anisotropy and microscopic structure in skeletal muscles using magnetic resonance.

The pulsed-gradient spin-echo (PGSE) nuclear magnetic resonance (NMR) method is used for detecting the diffusion of water molecules in biological tissues. Because tissues generally have diffusional anisotropy, their diffusion properties are denoted by a tensor. In this study, we evaluated the diffusional anisotropy and microscopic structure in atrophied skeletal muscles using the PGSE NMR method. The left sciatic nerve was severed in twelve 9-week-old rats. Neurotomy caused neurogenic muscular atrophy at the left gastrocnemius. At 2, 4 and 8 weeks after neurotomy, magnetic resonance signals were selectively acquired from a 2 x 2 x 2 mm(3) voxel, which was located on the left gastrocnemius. The diffusion tensor, the mean diffusivity (MD) and the fractional anisotropy (FA) were calculated from the signals. A theoretical model of the diffusion in muscles was derived from Tanner's equation. The muscle fiber diameter was estimated by fitting the model to the measured signals. The measurements were also performed for normal rats as controls. No significant difference was found in the MD and the estimated intracellular diffusion coefficient between the control group and the denervated group. The denervated group had significantly higher FA compared with the control group (P<.05). The estimated muscle fiber diameter of the denervated group was significantly smaller than the estimated value of the control group (P<.05). These differences were found at 8 weeks after neurotomy. The proposed method is effective for evaluating changes in the microscopic structure of skeletal muscles.