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 (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.

This study demonstrates that previous treatment with radiotherapy resection of well perfused lung parenchyma and excessive fluid load are high risk factors for the development of non-cardiogenic pulmonary edema and that patients for whom these factors are relevant should be closely monitored in their postoperative course.

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 cmH 2 O, 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 scelrosis patients should prompt diaphragm function tests. Eur Respir J 2000; 15: 332±337.

The application of negative expiratory pressure (NEP) at end expiration has been shown to cause reflex-mediated activation of the genioglossus muscle in awake humans. To test whether a reflex contraction of pharyngeal dilator muscles also occurs in response to NEP applied in early expiration, the effect on genioglossus muscle reflex activity of NEP pulses of 500 ms, given 0.2 s after the onset of expiration and during the end-expiratory pause, was assessed in 10 normal awake subjects at rest. The raw and integrated surface electromyogram of the genioglossus (EMGgg) was recorded with airflow and mouth pressure under control conditions and with NEP ranging from -3 to -10 cmH2O. Intraoral EMGgg was also recorded under the same experimental conditions in two subjects. The application of NEP at the end-expiratory pause elicited a consistent reflex response of EMGgg in seven subjects with a mean latency of 68 +/- 5 ms. In contrast, when NEP was applied at the onset of expiration, EMGgg reflex activity was invariably observed in only one subject. No relationship was found between steady increase or abrupt fall in expiratory flow and the presence or the absence of a reflex activity of genioglossus during sudden application of NEP at the beginning of expiration. Our results show that a reflex activity of genioglossus is elicited much more commonly during application of NEP at the end rather than at the onset of expiration. These findings also suggest that when NEP is applied in early expiration to detect intrathoracic flow limitation the absence of upper airways narrowing does not imply the occurrence of a reflex-mediated activation of genioglossus and vice versa.