Anabela Pinto

Respiratory assistance with a non-invasive ventilator (Bipap) in MND/ALS patients: survival rates in a controlled trial.

Noninvasive ventilatory assistance, in ALS patients, with the bilevel intermittent positive air pressure (Bipap) was studied, in a prospective and controlled trial, by the authors. Twenty ALS bulbar patients, fulfilling El Escorial criteria for probable or definite disease, were selected. For the follow-up all patients were submitted to evaluation with the Norris scale, modified Barthel score and an analog scale of life satisfaction, every 3 months. All patients were also submitted to respiratory functional testing (RFT). Ten of these patients were treated with palliative management (group I), the remaining ten patients received Bipap support (group II). Clinical evolution curves and clinical parameters were not statistically different in both groups, except for the percentage of actual predicted value of vital capacity (p < 0.03), showing a more advanced disease in group II patients. Analog scale of life satisfaction showed improvement in the group II, even after the beginning of respiratory insufficiency, though without significance probably due to the small sample size (p < 0.1). Since 6 patients in group II are still alive survival rates were compared with log rank test considering cumulative survivals with Kaplan-Meier estimates. Total survival and survival from diurnal abnormalities in gas exchange (survival 1) were significantly longer for group II (p < 0.006 and p < 0.0004, respectively). In spite of the small number of patients, preliminary results strongly support the importance of BIPAP in ALS patients, though further studies must go on in order to optimize the best time for introducing Bipap.

Nocturnal pulse oximetry: a new approach to establish the appropriate time for non‐invasive ventilation in ALS patients

Previous studies have supported non‐invasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS), indicating that it prolongs survival. However, criteria for the use of NIV are yet to be defined. The aim of the present study was to evaluate the potential use of nocturnal pulse oximetry (NPO) as a tool for determining the most appropriate time at which to initiate NIV in ALS patients. We conducted a prospective, comparative, historical‐controlled clinical study of 64 consecutive ALS patients. Group 1 (historical control group) comprised 44 patients, 14 women and 30 men, with a mean age of 60+/−13 years, in whom we used NIV after detecting early signs of diurnal respiratory insufficiency (RI). Group 2 had 20 ALS patients, 8 women and 12 men, with a mean age of 56+/−11 years, for whom we started NIV after detecting more than 15 periods of nocturnal desaturation/hour by NPO. All patients were periodically evaluated with Norris spinal and bulbar scores, respiratory function tests (RFT) and NPO at three month intervals for one year. They were subsequently followed until death or loss of autonomy from the ventilator. We compared survival time or time to loss of autonomy from the ventilator between both groups. Survival was longer in Group 2 (p<0.002). We concluded that NPO is a valuable screening test to establish the need for NIV. Our results also suggest that the early diagnosis of RI and the early use of NIV increase patient compliance with NIV.

A randomized, placebo-controlled trial of memantine for functional disability in amyotrophic lateral sclerosis

Abstract Our objective is to describe the results of a phase II/III, 12-months, double-blinded, single-centre, randomized, parallel (1:1), clinical trial performed to evaluate the efficacy and safety of memantine in ALS. Patients with probable or definite ALS of less than 36 months disease duration and progression over a one-month lead-in period were randomly assigned to placebo or memantine at 20 mg/day. The primary endpoint was 12-months ALSFRS decline. Forced vital capacity, manual muscle testing, visual analogue scale, quality of life, motor unit number estimation and neurophysiological index were the secondary endpoints. The number of patients included was based on the assumption of a 50% change in the ALSFRS decline. Safety and adverse events were evaluated. Sixty-three patients were included in the trial. Memantine did not show more adverse events or laboratory changes than placebo. Primary and secondary outcomes were not different between groups by intention-to-treat and per-protocol analysis. The most sensitive measurements were neurophysiological, which declined linearly over time. In conclusion, the results of this study show that memantine is well tolerated and safe in ALS patients. We did not observe any evidence of efficacy for memantine but we cannot exclude a positive outcome on survival.

Can amyotrophic lateral sclerosis patients with respiratory insufficiency exercise

The authors have shown in a recent paper that survival with amyotrophic lateral sclerosis (ALS) can be increased by the use of non-invasive methods of assisted ventilation (Bipap). However, the progression of muscle weakness was not affected and the quality of life was not positively enhanced. In ALS, reduced physical activity may partially be secondary to alveolar hypoventilation syndrome. This leads to deconditioning of ALS/motor neuron disease (ALS/MND) patients. The authors decided to investigate the possibility of reducing motor decline by exercising these patients to the anaerobic threshold, but simultaneously compensating the respiratory insufficiency with the Bipap STD. We conducted a controlled single blind study, exercising eight consecutive ALS/MND patients and used a control group of 12 ALS/MND patients. The patients were all evaluated during a 1 year period. Respiratory function tests (RFT) were performed at entry and then at 6 month intervals. Barthel, Functional Independent Mobility scale (FIM) and Spinal and Bulbar Norris scores were recorded every 3 months. There was a significant difference between the two groups with respect to FIM scores (P<0.03), but not Barthel scores (P<0.8). A slower clinical course (Spinal Norris score P<0.02) and a significant difference in the slope of the RFT (P<0.008) were observed in the treated group, suggesting that exercise may be beneficial in ALS patients once Bipap is used to control peripheral and muscle oxygenation.

Home telemonitoring of non-invasive ventilation decreases healthcare utilisation in a prospective controlled trial of patients with amyotrophic lateral sclerosis

Background Non-invasive ventilation (NIV) is an efficient method for treating respiratory failure in patients with amyotrophic lateral sclerosis (ALS). However, it requires a process of adaptation not always achieved due to poor compliance. The role of telemonitoring of NIV is not yet established. Objectives To test the advantage of using modem communication in NIV of ALS patients. Design Prospective, single blinded controlled trial. Population and methods According to their residence, 40 consecutive ventilated ALS patients were assigned to one of two groups: a control group (G1, n=20) in which compliance and ventilator parameter settings were assessed during office visits; or an intervention group (G2, n=20) in which patients received a modem device connected to the ventilator. The number of office and emergency room visits and hospital admissions during the entire span of NIV use and the number of parameter setting changes to achieve full compliance were the primary outcome measurements. Results Demographic and clinical features were similar between the two groups at admission. No difference in compliance was found between the groups. The incidence of changes in parameter settings throughout the survival period with NIV was lower in G2 (p<0.0001) but it was increased during the initial period needed to achieve full compliance. The number of office or emergency room visits and inhospital admissions was significantly lower in G2 (p<0.0001). Survival showed a trend favouring G2 (p=0.13). Conclusions This study shows that telemonitoring reduces health care utilisation with probable favourable implications on costs, survival and functional status.

Sleep characteristics of amyotrophic lateral sclerosis in patients with preserved diaphragmatic function

There are a number of sleep studies in amyotrophic lateral sclerosis (ALS), in general including a heterogeneous population of patients. We aimed to study sleep in a population of selected ALS patients by investigating nocturnal polysomnography (PSG) characteristics in ALS patients with normal respiratory function tests and preserved diaphragmatic innervation. Ninety‐two ALS patients were screened by percutaneous nocturnal oximetry (PNO). Eleven ALS patients with normal respiratory function tests, phrenic motor responses and preserved motor units on needle electromyography of the diaphragm, but abnormal PNO, were selected for PSG. REM was present in eight patients, but normal in only three. Three patients had mixed apnoea‐hypopnoea, severe in one. Seven showed a pattern of periodic mild O2 desaturation, which occurred in REM 3, REM and NREM 3 and in NREM sleep 1. One patient studied six months later had more severe changes in the second evaluation. In conclusion, the most common sleep disordered breathing was periodic mild O2 desaturation independent of the sleep stage (REM, NREM). This might represent central drive dysfunction or respiratory muscle fatigue in ALS.

Phrenic nerve conduction in amyotrophic lateral sclerosis

Respiratory failure accounts for the majority of deaths in amyotrophic lateral sclerosis (ALS). The main cause of respiratory failure is probably diaphragmatic weakness. In order to test the correlation between respiratory impairment and diaphragmatic function we studied the phrenic nerve conduction in 31 ALS patients. Our results showed that patients with respiratory symptoms, and decreased forced vital capacity with arterial PaO2/PaCO2 abnormalities, had more commonly increased phrenic nerve latencies or absent response due to severe diaphragm denervation than ALS patients without respiratory complaints. Diaphragmatic paresis commonly occurs during the course of ALS, and its presence and severity can be assessed by phrenic nerve studies. It is important to recognize the development of impairment in diaphragmatic function in order to prevent life-threatening complications.

Respiratory disorders in ALS: sleep and exercise studies

Sleep disruption in ALS/MND is related to hypoventilation and nocturnal O(2) saturation. Maximal inspiratory pressure (PI(max)) proved sensitive in predicting nocturnal O(2) saturation. However, PI(max) is highly dependent on patient collaboration; on the other hand Mouth Occlusion Pressure (MOP) is a reliable, non-volitional parameter index of central respiratory drive. Since exercise testing (ET) is also part of the assessment of ventilatory regulation the authors aimed to determine whether MOP and ET are sensitive and reliable parameters predictive of nocturnal O(2) saturation and clinical evolution. We conducted a Polysomnographic (PSG) study in two groups of 14 patients, selected according to their MOP level. Patients performed at admission an ET, Respiratory Function tests (RFT) and clinical evaluation with Norris spinal and bulbar scores (SNS and BNS). All patients in Group I (Low MOP) had decreased O(2) saturation during ET (P<0.001). Correlation study showed correlation between ET and MOP (R=0.6); PI(max) slope and PE(max) slope correlated with ET (R=-0.4; -0.6), respectively. ET also correlated with nocturnal O(2) saturation and SNS slope (R=0.8; -0.5), respectively. SNS and BNS slopes correlated with nocturnal O(2) saturation (R=-0.4; -0.7), respectively. The best correlations found were between MOP slope and BNS slope and SNS slope (R=0.8; 0.7), respectively. The high predictive values of MOP and ET at admission to nocturnal O(2) saturation (predicted value=80%) suggested the need of nocturnal pulse oximetry as a standard procedure. MOP and ET should also be used in evaluation protocols of ALS/MND.

Changes of the phrenic nerve motor response in amyotrophic lateral sclerosis: Longitudinal study

OBJECTIVE Phrenic nerve motor amplitude (Diaphr Ampl) is predictive of hypoventilation in amyotrophic lateral sclerosis (ALS). We aimed to evaluate its change over disease course and to correlate it to other measurements. METHODS Forty-nine unselected patients (35 men, 13 bulbar-onset, 56.5+/-8.9 years) with definitive or probable ALS were included. They were evaluated at entry (time 0) and 4-6 months (5.2+/-1.0) later (time 1) with: functional ALS rating scale (ALS-FRS) and respiratory subscore (ALS-FRSr); forced vital capacity (FVC); maximal inspiratory pressure (MIP); mean O(2) saturation overnight (SpO(2)mean); sniff maximal inspiratory pressure (SNIP); Diaphr Ampl and mean amplitude of the ulnar nerve response (ADM Ampl). RESULTS ALS-FRS, ALS-FRSr, Diaphr Ampl, FVC, SNIP, ADM Ampl (p<0.01) and SpO(2)mean (p<0.05) declined significantly. MIP did not change significantly (p=0.203). Coefficient of variation was similar for FVC, Diaphr Ampl, ADM Ampl and ALS-FRS but higher for SNIP. The percentage of change for Diaphr Ampl was significantly correlated to FVC and SNIP, but not to ADM Ampl or ALS-FRS. CONCLUSIONS Diaphr Ampl decreased significantly in a short period of time and its change is correlated to other respiratory tests. This test can be useful in patients with marked facial weakness or uncooperative. SIGNIFICANCE Diaphr Ampl is useful to monitor respiratory function in ALS patients and can be applied in clinical trials.

Percutaneous nocturnal oximetry in amyotrophic lateral sclerosis: Periodic desaturation

Percutaneous nocturnal oximetry (PNO) is useful to screen respiratory function in amyotrophic lateral sclerosis (ALS). PNO recordings of some patients disclose a periodical pattern of O2 desaturation (PP), whose significance is unknown. We aimed to characterize PP pattern, and we used a prospective study enrolling 261 consecutive ALS patients. Clinical, pulmonary and neurophysiological tests performed included: ALS functional rating scale, forced vital capacity (FVC), maximal inspiratory pressure (PImax), mouth occlusion pressure (MOP), phrenic nerve motor response, needle electromyography of the diaphragm, PNO, and sleep study. A total of 837 PNO recordings were analysed (3.2 recordings/patient) and 45 patients showed typical PP (17.2%). Four were excluded, 13 had normal diaphragm (group 1, G1), and in 28 the diaphragm was abnormal (G2). The two groups were comparable, apart from respiratory score, FVC and PImax which were lower in G2. In G1, REM sleep was absent and hypoventilation occurred at slow-wave sleep. Five patients in G1 were very spastic, had low MOP/FVC and a short survival. This study identified a subgroup of ALS patients (G1) with marked signs of upper motor neuron lesion, strong respiratory muscles, PP, low MOP/FVC ratio and poor prognosis. We speculate that they have a central respiratory dysfunction and deserve special care.