[Proposals from a French expert panel for respiratory care in ALS patients]. / Propositions formulées par un groupe d'experts français concernant la prise en charge respiratoire chez les patients atteints de sclérose latérale amyotrophique.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive diaphragm weakness and deteriorating lung function. Bulbar involvement and cough weakness contribute to respiratory morbidity and mortality. ALS-related respiratory failure significantly affects quality of life and is the leading cause of death. Non-invasive ventilation (NIV), which is the main recognized treatment for alleviating the symptoms of respiratory failure, prolongs survival and improves quality of life. However, the optimal timing for the initiation of NIV is still a matter of debate. NIV is a complex intervention. Multiple factors influence the efficacy of NIV and patient adherence. The aim of this work was to develop practical evidence-based advices to standardize the respiratory care of ALS patients in French tertiary care centres. METHODS: For each proposal, a French expert panel systematically searched an indexed bibliography and prepared a written literature review that was then shared and discussed. A combined draft was prepared by the chairman for further discussion. All of the proposals were unanimously approved by the expert panel. RESULTS: The French expert panel updated the criteria for initiating NIV in ALS patients. The most recent criteria were established in 2005. Practical advice for NIV initiation were included and the value of each tool available for NIV monitoring was reviewed. A strategy to optimize NIV parameters was suggested. Revisions were also suggested for the use of mechanically assisted cough devices in ALS patients. CONCLUSION: Our French expert panel proposes an evidence-based review to update the respiratory care recommendations for ALS patients in daily practice.

Proposals from a French expert panel for respiratory care in ALS patients.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive diaphragm weakness and deteriorating lung function. Bulbar involvement and cough weakness contribute to respiratory morbidity and mortality. ALS-related respiratory failure significantly affects quality of life and is the leading cause of death. Non-invasive ventilation (NIV), which is the main recognized treatment for alleviating the symptoms of respiratory failure, prolongs survival and improves quality of life. However, the optimal timing for the initiation of NIV is still a matter of debate. NIV is a complex intervention. Multiple factors influence the efficacy of NIV and patient adherence. The aim of this work was to develop practical evidence-based advices to standardize the respiratory care of ALS patients in French tertiary care centres. METHODS: For each proposal, a French expert panel systematically searched an indexed bibliography and prepared a written literature review that was then shared and discussed. A combined draft was prepared by the chairman for further discussion. All of the proposals were unanimously approved by the expert panel. RESULTS: The French expert panel updated the criteria for initiating NIV in ALS patients. The most recent criteria were established in 2005. Practical advice for NIV initiation were included and the value of each tool available for NIV monitoring was reviewed. A strategy to optimize NIV parameters was suggested. Revisions were also suggested for the use of mechanically assisted cough devices in ALS patients. CONCLUSION: Our French expert panel proposes an evidence-based review to update the respiratory care recommendations for ALS patients in daily practice.

Interaction between posture and maxillomandibular deformity: a systematic review.

Maxillomandibular deformity (MMD) and body posture appear to be correlated. However, no systematic literature review of the available evidence to support this correlation has been performed to date. The aim of this study was to conduct a systematic literature review on posture and MMD. This systematic literature review was registered in the PROSPERO database. Systematic searches of the MEDLINE, Scopus, Cochrane Library, and Web of Science databases were performed. In total, 13 clinical studies were included. Nine found a significant association between MMD and body posture or body balance: two studies showed a correlation between increased cervical lordosis and skeletal class III MMD, two studies showed an interaction between mandibular deviation and scoliosis, four studies demonstrated a significant association between lumbar column and pelvis anatomy and MMD, and one study found a correlation between displacement of the centre of mass and MMD. However, the level of evidence is low; the methods used to evaluate body posture and MMD were inconsistent. Orthognathic surgery could modify body posture. Although there seems to be an interaction between body posture and facial deformity, the number of studies is too small and the level of evidence too low to strongly support this association.

Long-term effectiveness and side effects of mandibular advancement devices on dental and skeletal parameters.

INTRODUCTION: Continuous positive airways pressure, generally used to treat obstructive sleep apnea-hypopnea syndrome (OSAHS), is not tolerated well by many patients. An alternative is to treat OSAHS with mandibular advancement devices (MAD). This research assesses the long term (> 2 years) effectiveness and the side effects on dental and skeletal parameters of these devices. MATERIAL AND METHODS: We selected 24 patients with moderate to severe OSAHS. All were treated with MADs for at least 2 years. We gathered cephalometric teleradiographs in centric relation and sleep recordings before and after the patients were treated. We evaluated the patients' apnea-hypopnea indexes (AHI) as well as their Epworth sleepiness scale (ESS) scores. We measured the inclination of the central incisors and the positions of the upper and lower jaws. RESULTS: Mandibular advancement devices were used for more than 2 years (3.9 ± 1.9 years). We observed a statistically significant decrease of the patients' AHI and their ESS scores. We also observed a modification of the inclination of the lower central incisors (+0.521; P = 0.047) and of the position of the maxilla (-0.287; P = 0.039). DISCUSSION: We demonstrated the clinical effectiveness of mandibular advancement devices for treating OSAHS, with a very low rate of side effects on dental and skeletal positions.

Residual sleepiness in obstructive sleep apnoea: phenotype and related symptoms.

The characteristics of residual excessive sleepiness (RES), defined by an Epworth score >10 in adequately treated apnoeic patients, are unknown. 40 apnoeic patients, with (n = 20) and without (n = 20) RES, and 20 healthy controls underwent clinical interviews, cognitive and biological tests, polysomnography, a multiple sleep latency test, and 24-h sleep monitoring. The marked subjective sleepiness in the RES group (mean ± sd score 16.4 ± 3) contrasted with moderately abnormal objective measures of sleepiness (90% of patients with RES had daytime sleep latencies >8 min). Compared with patients without RES, the patients with RES had more fatigue, lower stage N3 percentages, more periodic leg movements (without arousals), lower mean sleep latencies and longer daytime sleep periods. Most neuropsychological dimensions (morning headaches, memory complaints, spatial memory, inattention, apathy, depression, anxiety and lack of self-confidence) were not different between patients with and without RES, but gradually altered from controls to apnoeic patients without and then with RES. RES in apnoeic patients differs markedly from sleepiness in central hypersomnia. The association between RES, periodic leg movements, apathy and depressive mood parallels the post-hypoxic lesions in noradrenaline, dopamine and serotonin systems in animals exposed to intermittent hypoxia.

Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposis.

BACKGROUND: Topical steroids are first-line medication to control nasal polyposis (NP), a disease with long-term clinical course. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 microg twice a day (bd) after 1 month of treatment, and to compare FPANS 200 microg bd and FPANS 200 microg once a day (od) in maintenance and long-term treatment. METHODS: Double-blind, placebo-controlled, 8-month study with three treatment periods (1-month acute period followed with 1-month maintenance period and 6-month follow-up period) was carried out. Group 1 received FPANS 200 microg bd, during acute, maintenance and follow-up periods, Group 2 received FPANS 200 microg bd during acute period and FPANS 200 microg od during maintenance and follow-up periods, and Group 3 received placebo during acute and maintenance periods and FPANS 200 microg bd during follow-up period. Endpoints were change from baseline in clinic peak nasal inspiratory flow (PNIF), domiciliary evening PNIF, intensity of symptoms and polyposis grade. RESULTS: After acute period and maintenance periods, FPANS 200 microg bd was significantly more effective than placebo on all endpoints and more effective than FPANS 200 microg od after 1-month maintenance period on clinic PNIF, evening PNIF, obstruction, percentage of days with no sense of smell and percentage of nights with no disturbances. The two doses were similar on other endpoints. After the 6-month follow-up period, there was no difference between the two doses of FPANS at all efficacy endpoints. The safety profile of FPANS did not highlight any new or unanticipated adverse events. CONCLUSION: The study demonstrated the efficacy of FPANS 200 microg bd in acute treatment and FPANS 200 microg od as a sufficient dose to maintain a long-term efficacy in the treatment for NP.

Bilateral phrenic paralysis in a patient with systemic lupus erythematosus.

Respiratory manifestations of systemic lupus erythematosus (SLE) are frequent. They include respiratory muscle abnormalities, which have been implicated in the pathogenesis of the "shrinking lung syndrome" (SLS). We report the case of a patient with this syndrome, in whom diaphragmatic paralysis due to demyelinating phrenic lesions was diagnosed at the same time as SLE. Follow-up studies showed a favorable clinical and diaphragmatic outcome with corticosteroid therapy, but little change in spirometry. It is concluded that severe diaphragm palsy is possibly due to phrenic nerve lesions in SLE, and that the link between diaphragm dysfunction and the SLS is probably not a straightforward one.

Assessment of upper airway dynamics in awake patients with sleep apnea using phrenic nerve stimulation.

Phrenic nerve stimulation can reproduce during wakefulness the dissociation between upper airway and inspiratory muscles that is associated with obstructive sleep-related breathing disorders. This could provide a useful management tool in the study of passive upper airway (UA) dynamics during wakefulness in patients with the obstructive sleep apnea-hypopnea syndrome (OSAHS). To assess the feasibility of the technique in this setting, we studied the dynamics of diaphragm twitch-associated inspiratory flow in eight patients with OSAHS. Cervical magnetic stimulation (CMS) and bilateral anterior magnetic phrenic stimulation (BAMPS) were applied at end-expiration during exclusive nasal breathing. Electrical phrenic nerve stimulation (ES) proved not feasible. The driving pressure and the respiratory resistance at peak twitch esophageal pressure obtained at maximal stimulation intensity were significantly higher with BAMPS than with CMS. A twitch-flow limitation pattern was observed in seven of eight subjects; VI(max) values of flow-limited twitches obtained at 100% stimulation intensity was 0.81 +/- 0.5 L/s with BAMPS and 0.87 +/- 0.5 L/s with CMS (p = 0.4). The number of flow-limited BAMPS twitches dropped from an average 77.5% to 18.4% with nasal continuous positive airway pressure (CPAP) levels corresponding to the patient's home treatment. We conclude that (1) BAMPS is potentially a useful tool to evaluate the dynamics of flow through the passive UA in awake OSAHS patients, (2) BAMPS may be superior to CMS in evaluating UA properties in OSAHS.

Diaphragmatic dysfunction and dyspnoea in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive disorder of unknown origin. Respiratory involvement is the principal cause of death, and dyspnoea is a major source of discomfort. In this study, diaphragm function is described and its relationship with dyspnoea examined in 48 ALS patients (32 male, age 26-80 yrs). The detailed neurological and respiratory evaluation (clinical examination, pulmonary function tests, static pressures, mouth twitch pressures (Pm,t), electromyographic responses to phrenic nerve stimulation and cortical magnetic stimulation were analysed after stratification according to dyspnoea. Dyspnoeic (group I) and nondyspnoeic (group II) patients were similar, bulbar signs being more frequent in group I. Vital capacity was lower in group I (mean+/-SD 67.9+/-22.7 versus 87.9+/-15.6% of the predicted value, p=0.0028), as were maximal static inspiratory pressure (41+/-24 versus 60+/-27% pred, p=0.0242) maximal static inspiratory pressure (18+/-11 versus 32+/-14% pred, p=0.0042), and Pm,t (3.71+/-2.5 versus 7.26+/-3.45 cmH2O, p=0.0011). Abdominal (Abd) paradox and respiratory pulse were frequent in group I (15 of 25 and 14 of 25) but absent or rare in group II (0 of 23 and four of 23) (p<0.05). The electromyographic responses to phrenic and cortical stimulation were generally abnormal in group I but subnormal in group II. Multivariate analysis selected only signs of diaphragm dysfunction (namely, Abd paradox and abnormal electromyographic responses) as significant predictors of dyspnoea. It is concluded that dyspnoea in amyotrophic lateral sclerosis patients should prompt diaphragm function tests.

Sleep disorders and diaphragmatic function in patients with amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS), the progressive loss of upper and lower motor neurons leads to respiratory failure, often with predominant diaphragm dysfunction, and death. Because the diaphragm is the only active inspiratory muscle during rapid eye movement (REM) sleep, there is a high theoretical risk of respiratory disorders during REM sleep in patients with ALS. To assess this hypothesis, we studied sleep characteristics (polysomnography) in 21 patients with ALS, stratified according to the presence or absence of diaphragmatic dysfunction. Diaphragmatic dysfunction was defined as an absent or delayed diaphragm response to cervical or cortical magnetic stimulation, abdominal paradox, or respiratory pulse (Group 1, 13 patients). These patients did not differ in age, clinical course, or form (bulbar or spinal) from the eight others, who did not have diaphragmatic dysfunction (Group 2). REM sleep was reduced in Group 1 (7 +/- 7% of total sleep time; mean +/- SD) and normal in Group 2 (18 +/- 6%, p = 0.004). Apneas or hypopneas were rare in both groups. In Group 1, REM sleep was absent or minimal (less than 3 min) in five patients. An unusual and remarkable preservation of phasic inspiratory sternomastoid activation during REM was associated with longer REM sleep duration in six of the other patients with diaphragmatic dysfunction. Median survival time was dramatically shorter (217 d) in Group 1 than in Group 2 (619 d, p = 0.015).

Cervical magnetic stimulation as a method to discriminate between diaphragm and rib cage muscle fatigue.

Inspiratory muscle fatigue can probably determine hypercapnic respiratory failure. Diaphragm fatigue is detected by electrical phrenic stimulation (ELS), but there is no simple tool to assess rib cage muscle (RCM) fatigue. Cervical magnetic stimulation (CMS) costimulates the phrenic nerves and RCM. We reasoned that changes in transdiaphragmatic pressure twitch (Pdi,tw) with CMS and ELS should be different after selective diaphragm vs. RCM fatigue. Five volunteers performed inspiratory resistive tasks while voluntarily uncoupling diaphragm and RCM. Baseline Pdi,twELS and Pdi,twCMS were 28.57 +/- 1.68 and 32.83 +/- 2.92 cmH2O. After selective diaphragm loading, Pdi,twELS and Pdi,twCMS were reduced by 39 and 26%, with comparable decreases in gastric pressure twitch (Pga,tw). Esophageal pressure twitch (Pes,tw) was better preserved with CMS. Therefore Pes,tw/Pga,tw was lower with ELS than CMS (-1.24 +/- 0.16 vs. -1.73 +/- 0.11, P = 0.05). After selective RCM loading, there was no diaphragm fatigue, but Pes,twCMS was significantly reduced (-30%). These findings support the role of rib cage stiffening by CMS-related RCM contraction in the ELS-CMS differences and suggest that CMS can be used to assess RCM fatigue.

Influence of neck muscles on mouth pressure response to cervical magnetic stimulation.

Measurement of mouth pressure (Pm) in response to electrical phrenic nerve stimulation (Es) provides a simple noninvasive means to assess diaphragm function. An even simpler measure would be to use the Pm twitch response (Pm,t) to cervical magnetic stimulation (CMS) rather than to Es. Because CMS coactivates the diaphragm and inspiratory neck muscles (INM), CMS-Pm,t accurately reflects diaphragm function only if the corresponding INM contraction does not produce inspiratory pressures by itself. In patients with recent-onset bilateral diaphragm paralysis, it has been demonstrated that CMS-Pm,t was indeed zero; however, INM hypertrophy could change this situation and lead CMS-Pm,t to overestimate the performance of the diaphragm. To address this issue, we studied nine patients with amyotrophic lateral sclerosis (ALS) who had evidence of diaphragmatic paralysis and compensatory hypertrophy and hyperactivity of inspiratory neck muscles. The response to CMS was described in terms of diaphragm electromyogram (EMG), Pm, and abdominal (AB) and rib cage (RC) motion. No EMG response to CMS could be observed in most cases, and CMS was always associated with AB paradox. Nevertheless, a negative Pm,t swing was recorded with an amplitude of -2.6 +/- 1.0 cm H2O (mean +/- SD). We conclude that inspiratory neck muscle hypertrophy can significantly influence the Pm response to CMS. This should be taken into account when using the CMS-Pm combination in patients with possible chronic diaphragm dysfunction.

Neuromuscular blockade with acute respiratory failure in a patient receiving cibenzoline.

Cibenzoline is a class Ic antiarrhythmic agent that can be used to treat supraventricular arrhythmias. A case is reported of cibenzoline overdose in a patient with impaired renal function, leading not only to the usual cardiac and metabolic symptoms (bradycardia and hypoglycaemia), but also to a myastheniform syndrome with acute respiratory failure. Neuromuscular blockade was demonstrated by repetitive supramaximal stimulation of the median nerve, and diaphragmatic involvement was evidenced by applying the same protocol to the phrenic nerve. Muscle strength recovered as serum cibenzoline levels decreased, allowing the patient to be weaned from the ventilator. This observation suggests that cibenzoline, like other antiarrhythmic agents, can be responsible for neuromuscular blockade, and should therefore be used with caution in patients with neuromuscular and respiratory diseases or with impaired renal function.

Comparison of magnetic and electrical phrenic nerve stimulation in assessment of phrenic nerve conduction time.

Cervical magnetic stimulation (CMS), a nonvolitional test of diaphragm function, is an easy means for measuring the latency of the diaphragm motor response to phrenic nerve stimulation, namely, phrenic nerve conduction time (PNCT). In this application, CMS has some practical advantages over electrical stimulation of the phrenic nerve in the neck (ES). Although normal ES-PNCTs have been consistently reported between 7 and 8 ms, data are less homogeneous for CMS-PNCTs, with some reports suggesting lower values. This study systematically compares ES- and CMS-PNCTs for the same subjects. Surface recordings of diaphragmatic electromyographic activity were obtained for seven healthy volunteers during ES and CMS of varying intensities. On average, ES-PNCTs amounted to 6.41 +/- 0.84 ms and were little influenced by stimulation intensity. With CMS, PNCTs were significantly lower (average difference 1.05 ms), showing a marked increase as CMS intensity lessened. ES and CMS values became comparable for a CMS intensity 65% of the maximal possible intensity of 2.5 Tesla. These findings may be the result of phrenic nerve depolarization occurring more distally than expected with CMS, which may have clinical implications regarding the diagnosis and follow-up of phrenic nerve lesions.

Assessment of the motor pathway to the diaphragm using cortical and cervical magnetic stimulation in the decision-making process of phrenic pacing.

BACKGROUND: Phrenic nerve pacing is a recognized substitute to positive pressure ventilation via tracheotomy in patients with high cervical cord lesions or central hypoventilation. Although its indications are infrequent, reliable strategies need to be used in the determinations of patients who may benefit from this treatment; contraindications should be carefully respected. STUDY OBJECTIVES: To determine whether modern and noninvasive means to study the motor pathway to the diaphragm, namely cortical magnetic stimulation (CxMS) and cervical magnetic stimulation (CMS), can contribute to the selection of patients who may benefit from phrenic pacing. DESIGN AND SETTING: Prospective study (18 months), on a consecutive basis, of patients referred for possible phrenic pacing to a 10-bed ICU associated with a respiratory neurophysiology laboratory. PATIENTS: Seven patients (high cervical cord injury, n = 5; central hypoventilation following neurosurgery, n = 1; idiopathic acquired central hypoventilation, n = 1). INTERVENTION, MEASUREMENTS, AND RESULTS: Electromyography of the diaphragm and transdiaphragmatic pressure were assessed in response to CxMS and CMS. In three cases, no interruption of the corticodiaphragmatic pathway was evidenced, the decision of pacing was postponed, and the patients eventually recovered a spontaneous breathing activity. In two cases, the diagnosis of irreversible peripheral phrenic dysfunction was reached and pacing was denied. In two cases, complete interruption of the corticodiaphragmatic pathway and integrity of peripheral conduction led to the decision of phrenic pacemaker implantation. CONCLUSION: CxMS and CMS can be used to refine the assessment of patients proposed for phrenic pacing. CxMS can possibly identify those in whom there is a possibility for eventual recovery, and therefore substantiate a decision to postpone the pacing.

Assessment of the voluntary activation of the diaphragm using cervical and cortical magnetic stimulation.

The twitch occlusion technique is a promising tool for use in accessing central drive to the diaphragm and determining maximal transdiaphragmatic pressure (Pdi) from submaximal efforts. It clinical use is limited by difficulties inherent to bilateral electrical stimulation (BES) of the phrenic nerves. This study was designed to revisit the technique using cervical magnetic stimulation (CMS). In addition, the effects of a voluntary contraction on diaphragm response to magnetic stimulation of the cortex (CxMS) were studied. Seven volunteers aged 23-33 yrs were studied. Pdi was determined at relaxed functional residual capacity (FRC) in response to BES (Pdi,P-ES) and CMS (Pdi,p-CMS), and the effects of an increasing voluntary contraction (Pdi, vol) were assessed, The same procedure was applied to CxMS. Pdi,p-CMS at relaxed FRC was 27.5 +/- 2.2 cmH2O (mean+/-SEM), about 20% higher than Pdi,p-ES, and reported previously. Pd,p-CMS linearly decreased with Pdi, vol, and six out of seven subjects were capable of producing voluntary contractions sufficient to extinguish the twitch. More complex patterns were observed with CxMS. Cervical magnetic stimulation provides diaphragmatic twitch occlusion data very similar to bilateral electrical phrenic stimulation. Magnetic stimulation, be it cervical or cortical, could probably be helpful for the assessment of central and peripheral mechanisms of diaphragmatic dysfunction in the clinical setting.