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Breathing disorders during sleep in myasthenia gravis.

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Breatlvng Disorders
during Sleep in Myasthenia Gravis
M. A. Quera-Salva, MD,* C. Guilleminault, MD,? S. Chevret, MD,$ G. Troche, MD,"
C. Fromageot, MD," C. Crowe McCann, MD," R. Stoos, MD,?
J. de Lattre, MD," J. C. Raphael, MD,* and Ph. Gajdos, MD"
~~~~
~~~~~~~
~~
~
Twenty consecutive patients (16 women and 4 men), with a mean age of 40 years, who were diagnosed and treated
for myasthenia gravis were enrolled in a prospective investigation aimed at determining the amount of respiratory
disturbance occurring during sleep while they received treatment. Patients were clinically evaluated to determine
body mass index, presence of upper airnay anatomical abnormalities, level of functional capacity and activity scored
from 1 to 5 , and presence of sleep-related complaints. They underwent daytime pulmonary function tests, determination of mavimal static inspiratory pressure, measurement of transdiaphragmatic pressure, and measurement of arterial
blood gas levels. Polygraphic monitoring during sleep, evaluating respiration and oxygen saturation, was also performed. RrsuIts indicated that in the studied population, all subjects had evidence of daytime diaphragmatic weakness
as demonstrated by transdiaphragmatic pressure measurements, independent of the degree of autonomy and functional
capacity and activity level reached. Older patients with moderately increased body mass index, abnormal total lung
capacity, and abnormal daytime blood gas concentrations were the primary candidates for development of diaphragmatic sleep apneas and hypopneas, and oxygen desaturation of less than 9096 during sleep. However, these clear
indicators were not found in all subjects with sleep-related disordered breathing. Rapid-eye-movement sleep was the
time of highest breathing vulnerability during sleep. Sleep-related complaints may also help identify subjects at risk
for abnormal breathing during sleep, even when daytime functional activity is judged normal.
Quera-Salva MA, Guilleminault C, Chevret S, Troche G , Fromagcot C, Crowe McCarin C ,
Stoos R, de Lattre J, Raphael JC, Gajdos Ph. Breathing disorders during :ilecp
in myasthenia gravis. Ann Neurol 1932;3 1:80-32
Myasthenia gravis (MG) is characterized by recurrent
episodes of weakness due to the fatigability of voluntary muscles. In this condition, IgG autoantibodies
bind to acetylcholine receptors and interfere with neuromuscular transmission { 1). Diaphragm and accessory
respiratory muscles may be involved, and respiratory
failure has been observed during exacerbations of the
syndrome [2, 33. In the recent past, an increased interest in sleep-related breathing led to the investigation
of patients with neuromuscular disorders during nonrapid-eye-movement (NREM) sleep and rapid-eyemovement (REM) sleep. We present the results of a
bicenter study of 20 patients with MG who were investigated during wake and sleep. The aims of the investigation were to assess the presence of breathing
disorders during sleep and to determine whether a correlation existed between daytime pulmonary function
and any sleep-related breathing disorder.
Materials and Methods
Criteria f i r Inclzcszon
From the 'HBpital Raymond PoincarC, Centre Hospitalo-Universiraire Paris-Ouest, Garches, France; ?Stanford University Medical
School, Stanford, CA; and the $Department de Biostatktique et
Informatique, HBpitaJ St-Louis, Paris, France.
Received Apr 26, 1990, and in revised form Feb 14 and Jun 27,
1991. Accepted for publication Tun 29. 1991.
The study was designed as a prospective investigation, during
wakefulness and sleep, of patients with MG. Informed consent was obtained from each patient. Each consecutive patient who was seen over a 12-month period and fulfilled the
following criteria was included in the study:
1. Each patient had to have generalized MG. The diagnosis
of M G had to have been based on findings from clinical
history, clinical examination, electromyography, and pharmacological testing. (Circulating antiacetylcholine receptor antibodies might have been measured, but this t8est
was not a prerequisite for inclusion.)
2. All patients had to have a stable clinical status and wellcontrolled MG during wakefulness, with no change in
treatment for at least 8 months. Patients would be studied
while they received their currently prescribed medications.
Address correspondence to D r Quera-Salva, Service de Rkanimarion
Medicale, HGpital Raymond Poincare, 104, bd Raymond PoincarG.
92380 Garches, France.
86 Copyright 0 1992 by the American Neurological Association
Table 1 . Clinical Characteristics and Pulmonary Function Test Results of the Patient Population
Patient
No.
Age
(yr)
22
31
1
2
3
4
5
56
49
68
28
30
24
49
29
53
39
52
59
53
36
27
40
37
44
6
7
8
9
10
11
12
13
14
I5
16
17
18
19
20
Sex
BMI
(kg/cm2)
F
F
F
F
M
F
F
F
F
F
F
F
M
M
F
F
F
M
F
F
19.5
15.0
32.0
30.0
29.5
16.5
20.0
22.0
20.0
24.0
25.0
17.5
28.0
23.5
19.5
16.0
18.5
22.0
23.0
23.5
Duration
since Diagnosis
of Disease
(yr)
2
2
2
28
4
4
9
10
11
8
15
7
4
4
23
FC
TLC(%)
FRC(%c)
2
2
3
3
3
4
3
2
2
110
76
75
72
49
84
94
75
109
83
92
73
68
92
95
113
100
53
1
4
2
3
1
3
3
1
2
1
9
2
2
1
8
12
100
62
110
103
47
132
92
10 1
109
80
72
75
111
92
60
112
114
100
102
78
74
68
Pao,
(mmHg)
Paco,
(mmHg)
Pdi Muller"
(cmH20)
95
90
81
75
70
90
92
96
84
85
79
69
80
78
87
89
88
84
81
78
38
37
38
47
45
40
40
39
41
37
39
56
44
33
44
38
38
39
40
40
20
-
23
10
-
32
38
23
6.5
30
8
30
18
37
40
49
21
25
20
"See texr for description.
FC
=
functional capacity and activity (I-normal, 5-completely incapacitated); TLC = total lung capacity, expressed in % of predicted; FRC
9T of predicted; Paoz = arterial oxygen pressure; Pam, = arterial carbon dioxide pressure.
= functional residual capaciry in
3. The final selection criterion used was different for the
two groups, as the clinics from which the patients were
recruited had different orientations. The French patients
came from an intensive care unit follow-up clinic and all
of them had a history of at least one episode of acute
respiratory distress that required intubation. They were
not enrolled as a result of sleep complaints. The Stanford
patients came from a neurology clinic and were recruited
on the basis of having complaints of breathing problems
during sleep.
Patient Populution
During the 12-month period considered (from June 1988 to
June 1989), 20 patients fulfilled the inclusion criteria and
entered the study. There were I 5 French and 5 American
patients, including 16 women and 4 men. The French patients were recruited from a pool of 104 patients with M G
seen in the clinic during the same period. Eight American
patients with M G were seen during the 12 months and 5
fulfilled the selection criteria for the study. The mean age
was 4 1 & 13 years (range, 22 to 6 8 years). The mean duration
of MG was 7 -t 5.5 years. Body mass index (BMI) was calculated using Khosla and Lowe's formula { 4 ] , weight in kilograms times 10,00O/(height in centimeters)'. The mean was
22 i- 5 kg/m2 and the range, 15.0 to 32.0 kg/m2; 28 to 33
kg/m2 was considered to be moderate obesity. Four patients
had a BMI in this range (Table 1).
All patients received daytime treatment for MG: All received anticholinesterase medications (pyridostigmine bromide or ambenonium chloride), 9 also received corticosteroids, and 13 patients had had a thymectomy. In each case,
the last anticholinesterase medication was taken at bedtime.
Procedure
After a review of the clinical history (including sleep-related
symptoms) and a clinical evaluation, including examination
of the upper airways, and grading of functional capacity and
activity level on a 5-point scale (from 1, complete remission,
to 5, major deficit without autonomy), all patients underwent
pulmonary function tests (PITS)during the daytime. PFTs
were performed while the patient was in a sitting position
and included spirometry, measurement of functional residual
volume (FRC) by the helium dilution technique, arterial
blood gas levels determined from blood samples drawn
within 2 hours of awakening, measurement of transdiaphragmatic pressure (Pdi), and maximal static inspiratory pressure
(Pi max, performed according to Black and Hyatt's technique
[ 5 , 6 } ) . Pi max was considered to be reduced when it was
less than 75% of that predicted 15, 61.
The Pdi was measured using Lapporta and Grassino's technique [7}, with a differential transducer connected to gastric
and esophageal balloons (Pdi: gastric pressure-esophageal
pressure). Pdi values at rest and expiratory pressure were
taken at the zero level. In addition to spontaneous breathing,
Quera-Salva et al: Breathing Disorders during Sleep in MG 87
patients were asked to perform a maximal inspiratory effort
against a closed glorris (Pdi during the Muller maneuver)
[7]. These maneuvers were repeated several times until a
best-obtained result had been reproduced. Patients were allowed to rest between each trial. The so-called “diaphragmatic fatigue” level (Pdi critical = Pdi/Pdi Muller > 40%)
was then calculated using Roussos and Macklem’s formula
IS]. Pdi and Pi max were measured with biofeedback, the
order being at random.
Nocturnal Pobgraphic Recording
Electroencephalograms (EEG) (C3/A, and C4/A, derivations), electro-oculograms, chin electromyograms, and
electrocardiograms (modified V, lead) were systeniatically
recorded. Airflow was measured by buccal and nasal thermistors. Respiration was measured by uncalibrated, inductive
respiratory plethyiimography (Respitrace, Anrlsley, NY),
aith, in addition, esophageal pressure recording and/or measurements of the accessory respirarory muscles and diaphragm with a nonintegrated electromyogram, using subcutaneous needle electrodes. Oxygen saturation (SaC),) was
measured by oxinietry at the finger (Biox-Ohmeda TM).
Data Analysi,
Sleep and sleep stages were scored following the international criteria of IRechtschaffen and Kales [9]. Apnea was
defined as a cessation of airflow at the nose and mouth for
at least 10 seconds. Hypopnea was defined as a reduction in
airflow by at least 50% associated with a decrease in SaO,
of at least 4% below the preceding baseline. Apneas and
hypopneas were characterized as central or diaphragmatic by:
(1) a decrease or absence of thoracoabdominal efforts, and (2)
a decrease or absence of the negative inspiratory esophageal
pressure deflection and/or a decrease or absence of accessory
respiratory muscle activity.
Several indices were calculated: (a) the classic respiratory
disturbance index (RDI), that is:
No. of apneas + No. of hypopneas
Total sleep time
X
60;
(b) the REM slcep RDI (RDI REM), that is, an index of
respiratory disturbance during total REM sleep time, (c) the
percentage of tclral sleep time (TST) with an SaO, of less
than YO‘/, that is, the percentage of time spent during sleep
with an SaOz of less than 90%, and (d) the SaO, 90 index
and SaOl 80 index, that is, the number of decreases in SaO,
below 90(/1 and below 80% during total sleep time [lo]
Statis&-al Analysis
Statistical analysis was performed using the SAS statistical
software (SAS Institute, Carey, NC). Comparisons between
patients with or without severe oxygen desaturacion during
sleep, called group A and group B, respectively, were based
o n the nonparametric Wilcoxon test I1 11. Relationship between breathing indices during sleep, clinical data, and daytime PET results was tested using the nonparametric Spearman rank test. However, considering the small sample size,
we computed the Tukey’s Jacknife estimates of the correlation coefficient, in order to provide a better estimate [ 12, 131.
Results are expressed as mean 5 standard deviation (SD).
88 Annals of Neurology
Vol 31 No 1 ,January 1992
Results
Clinical Status
Patients’ clinical status is reviewed in Table 1. Eight
patients had a score of 3 (out of a possible 5) or more
on the functional scale (i.e., partial activity due to MG),
7 patients had a score of 2 (i.e., minimal deficit with
normal activity), and all others were considered to be
in remission with no deficit during the daytime with
treatment intake (score 1).
Sleep Complaints
Twelve patients (Patients 3, 4, 5, 10, 12, 13, and 15
through 20) reported disrupted nocturnal sleep. Most
commonly, patients reported waking up in the middle
of the night and during the early-morning hours with a
sensation of breathlessness. The sleep complaints may
have existed for as long as 10 years in some patients.
However, nocturnal sleep disturbances were always
noted after the onset of MG. Four (Patients 3, 4, 5,
and 12) of the 12 patients also reported daytime somnolence, and 4 (Patients 3 , 4, 12, and 15) had morning
headaches, symptoms often seen in connection with
repetitive deep apneas.
Only 1 male patient (Patient 13) presented a history
of snoring over the years, and he had a long soft palate
with redundant soft tissues, suggesting an anatomical
abnormality of the upper airway.
Pulmonary Function Testing (see Table I )
Patients’ mean vital capacity was 80 -+ 17% of predicted (range, 5 1-1 12%), the mean total lung capacity
(TLC) was 84 5 16% of predicted (range, 49-1 lo%),
mean residual volume was 104
15% of predicted.
(range, 59-110%), and FRC was 91 5 23.5% (range,
47- 132%). Nine patients had a restrictive respiratory
syndrome (TLC < 80% of predicted).
Daytime arterial blood gas levels were within the
normal range in 17 subjects; however, 3 patients had
hypoxia and hypercapnia. The mean Pi max was 7 1.5%;
of predicted (range, 27 to 100%). Pi max was considered to be within the range of predicted values
(> 75% of predicted) in 11 patients (Patients 1, 3 , 6,
8, 9, 11, and 15 through 19). Pdi was not measured i n
3 patients who refused to undergo the test. Pdi wais
reduced in all 17 patients in whom it was measured.
Normal values of the Muller maneuver Pdi range from
91 to 141 cm H 2 0 [7]. In our patients, the mean
Muller Pdi was 26.5 cm H,O (range, 6.5 to 49 CIS-I
H20), indicating diaphragmatic weakness at the moment of examination in all subjects studied.
*
Polygraphic Monitoring during Sleep (Table 2)
Mean TST was 382 -+ 70.5 minutes (range, 212-525
min), mean percentage of stage 1 NREM sleep was
17.5% (range, 8-38%), mean percentage of stages 3
and 4 NREM (slow-wave) sleep was 12% (range,
Table 2. Polygraphic Monitoring Results
Patient
TST
No.
(min)
% REM
5
7 s3-4
RDI
REM RDI
52 TST SaO, < 90%
433
431
418
363
446
525
453
2 12
369
298
340
450
355
272
349
40 1
396
406
378
361
17.7
22.0
14.0
15.0
14.0
17.0
20.8
32.1
10.8
26.3
17.0
9.9
10.9
15.0
13.0
17.0
18.0
15.0
16.5
14.0
14.5
23.0
4.3
15.0
17.0
15.0
10.4
32.8
12.0
7.3
17.3
11.0
11.7
26.7
14.5
4.0
6.0
0.0
0.0
0.0
5.0
13.0
11.5
0.0
0.5
0.0
3.4
2.0
0.7
18.0
6.5
1.3
7.0
9.0
8.0
9.0
11.0
10.0
0.0
0.0
35.0
44.2
70.0
0.0
0.0
0.0
10.0
0.0
3.9
85.0
24.5
0.0
53.0
30.0
30.0
42.0
46.0
36.0
0.0
0.0
19.5
50.0
58.7
0.0
0.0
0.0
0.0
0.0
0.0
13.3
1.4
1.5
3.0
1.7
1.5
1.9
2.6
2.2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
0.9
0.0
~~
~~~~
TST = total sleep rime, % FGM = percentage of total sleep time spent in rapid-eye-movement (REM) sleep, 9 S-3-4 = percentage of TST
spent in stages 3 or 4 non-REM, RDI = respiratory disturbance index, REM RDI = RDI during total REM sleep, 9 TST Sa02 < 90% =
percentage of total sleep time spent with saturated oxygen level below 90%
0-332), and mean percentage of total REM sleep was
17(2 (range 9.9-32.I%). These results indicate a moderately disturbed nocturnal sleep [ 141, with an overall
increase in stage 1 NREM sleep, and a decrease in
stages 3 and 4 NREM and REM sleep percentages.
This sleep disturbance must, at least in part, be related
to the examination conditions and to first-night effect.
Investigation of breathing during sleep showed that
11 patients had an RDI of 5 or higher; 4 of them had
an RDI greater than 10. A raised REM sleep RDI
(REM RDI > lo), with a mean REM sleep RDI of 45
(range, 30 to 70), was also seen in these 11 patients,
indicating that they had a significant number of apneas
and hypopneas during REM sleep. All 11 patients, with
the exception of Patient 13, who presented a predominance of mixed and obstructive apneas and hypopneas,
had diaphragmatic (central) apneas and hypopneas.
SaO, measures showed that these respiratory disturbances were associated with decreases in oxygen saturation.
When the SaO, was examined during sleep, it was
found that 12 patients passed greater than 1% of their
TST with an SaO, of less than 90%. This group of 12
patients comprised the 1I patients who had an RDI of
5 or higher and 1 patient who did not have a pathological RDI.
This group of 12 patients with decreases in SaO,
during sleep can be divided into two subgroups:
Subgroup A comprised 8 patients who
spent from 1 to 3% of their TST with an SaO, of less
than 909%.Of these 8 patients, 6 patients (Patients 15
through 20) presented central-type apneas and hypopneas exclusively related to REM sleep and SaO,
dropped mildly in association with these respiratory
disturbances. Patient 14 presented non-EM-related
central-type apneas and hypopneas, and spent 1.5% of
TST with an SaO, of less than 90%. Patient 13, who
had signs and symptoms of “obstructive sleep apnea
syndrome” (OSAS), presented obstructive sleep apneas at the time of polygraphic recording, which occurred predominantly during stages 1 and 2 NREM
sleep. His breathing abnormalities during sleep were
thought to be, at least in part, related to the upper
airway abnormality and not entirely due to MG. The
6 patients with REM sleep-related respiratory disturbances and mild decreases in SaO, in association with
diaphragmatic apneas had nighttime arousals associated
with the predominantly REM sleep respiratory events
and complaints of nocturnal disrupted sleep.
SunGRouP A .
n. Subgroup B included 4 patients (Patients 3, 4, 5, and 12) who presented a more severe
condition, spending an average 35.5% of TST (range,
13.3-58.7s) with an SaO, of less than 90%. T h e nocturnal polygraphic investigation indicated that 3 (Patients 4, 5, and 12) of these 4 patients had a clear
SUBGROUP
Quera-Salva et al: Breathing Disorders during Sleep in MG
89
Table 3 . Correlation between Total Lung Capacity and
Respiratory Disturbance Index: Potential Influence of
Indit miduar' Obsewations
2o
1
7
2
16
Patient
No.
1
2
2
4
5
6
7
I
8
9
10
11
12
13
14
15
16
17
18
19
20
Partid Spearman
Correlation Coefficients"
- 0.404
-0.513
-0.455
- 0.398
-0.388
- 0.484
- 0.481
-0.530
- 0.475
-0 . 4 3
- 0.482
- 0.401
- 0.494
- 0.482
-0.526
-0.529
-0.527
-0.452
- 0.398
- 0.408
"Caku1att.d for cdch patient o n the remaining 19 patients.
central-type sleep apnea syndrome f l r j ) . They presented a combination of clinical complaints (nocturnal
disrupted sleep, daytime somnolence, and morning
headaches) with polygraphic abnormalities including a
significant RDI (RDI = 13.0, 11.5, and 18.0, respectively) and a decrease in SaO, (percentage of TST with
an SaO, of less than 90% of 50.0, 58.7, and 13.3%,
respectively). Patient 3 had a predominantly REM
sleep-related central type of respiratory events (RDI
= 5 ; REM RDI = 35) with a combination of hypoventilation and apneas and hypopneas, with a lower SaO,
SaO, < 70% := 19.5).
baseline during sleep (2,
Cowelution of Test Results
Duration of disease and level of functional capacity
showed no correlation with disturbed breathing during
sleep or decrease of SaO, during sleep, hut age correlated with the REM sleep RDI (Spearman coefficient,
r = 0.48, p = 0.03) and with percentage of TST with
an SaO, less than 90% ( Y = 0.57, p := 0.009). In
addition, BMI was correlated to age ( Y = 0.60, p =
0.005). The older the subjects, the greater the risk
of presenting an elevated REM RDI and an increased
amount of time spent with an SaO, less than 90%.
Groups A and B were thereafter compared. Slight
imbalances, which were not significant statistically,
were observed between the two groups. They con90 Annals of Neuroiogy Voi 3 1 N-o 1 January 1992
Correlation between total lung capacity ITLCI and respiivatory
disturbance index (RDIi, calculatedfor each subset oJ 19 patients. Each point corresponds t o the &set of 19 patient.! and
the number indicates the exrluded pdient. ?'he partial Spearman correlation codjcient ii indicated in Table .?.
sisted of older patients in Group B, where the mean
age was 54 versus 37 years in Group A ( p = 0.07),
and higher BMI in Group B, where the mean BMI
was 20 versus 27 in Group A ( p = 0.08).
Restrictive lung disease, as determined by TLC,correlated negatively with RDI ( Y = -0.466, p = 0.04),
with REM RDI ( Y = --0.448, p = 0.05), anal with
indices of SaO, decreases, the highest correlation being
against the percentage of TST spent with an SaO, of
less than 90% ( r = -0.524, p = 0.02). In order to
assess the influence of each subject, we reperformed
the latter analyses and examined the effect on the body
of data that resulted by omitting each patient. Thus,
Spearman correlation coefficients were calculated for
every subset of 19 patients (Table 3 ) , and then an overall correlation coefficient was estimated by computing
the mean of the 20 partial coefficients. It appeared that
these Jacknife estimates did not differ markedly from
those previously shown. T h e Figure displays the plot
of TLC against RDI, indicating for each patient the
value of the correlation coefficient that resulted from
omitting that subject. The Jacknife correlation coefficient between TLC and RDI was unchanged I(Y =
-0.465, p = 0.04). T h e correlation of TLC against
percentage of TST spent with an SaO, of less than
90%; yielded similar results (corrected r = - 0.5.23, p
= 0.02). Finally, the negative correlation between TLC
and REM RDI was still observed, but statistical significance disappeared (corrected r =; - 0.40 1, p = 0.08).
Daytime arterial blood gas concentrations were altered in 3 Group B patients. They had dayrime hypoventilation with combined daytime hypoxia and hypercapnia.
Measurements of daytime diaphragmatic efforts
(Muller Pdi, Pdi critical) and Pi max measurements
showed no correlation with RDI, nor with indices of
desaturation during sleep. All 17 patients tested had a
lower-than-expected Muller Pdi, and this measurement
could not differentiate patients with and those without
disordered breathing during sleep.
Discussion
Sleep studies are rarely performed on patients with
MG, and patients who appear to be stable during the
daytime are considered to have well-controlled disease.
However, patients with M G may have sleep-related
complaints such as sleep disruption [ 161, nocturnal
awakenings, early-morning awakenings, and daytime
somnolence, which may be related to their poorly controlled muscle disorder during sleep, with heightened
problems during REM sleep. All of our patients with
REM-related respiratory events complained of disturbed nocturnal sleep, with a sensation of breathlessness. All of the Group B patients also complained
of daytime somnolence, and 3 of the 4 had earlymorning headaches.
A patient may have MG and an abnormality of the
upper airway, which may lead to development of
OSAS, as occurred with Patient 13. But our study emphasizes that this is not the rule. All other patients with
sleep-related disturbed breathing had diaphragmatic
(central-type) apneas and hypopneas during sleep, as
already indicated by Shiozawa and colleagues [ 17) in
6 of 10 stable, daytime-well-controlled patients with
MG. The fact that the respiratory events were mostly
diaphragmatic may be related to the chronic impairment of diaphragmatic and accessory respiratory muscles. Mier-Jedrze jowicz and associates [ 3 ] reported
that a severe impairment of respiratory muscles may
exist in patients with MG, even when the involvement
of other skeletal muscles is mild.
Our patients had a significant reduction of Pdi and
Muller Pdi. At the same time, the values for the Pi
max were often at the lower limit of normal. These
discordant results may be explained by a poorly functioning diaphragm in the presence of normally functioning intercostal and accessory muscles. However,
the Pdi maneuvers are difficult to perform, which may
also have contributed to the results. The diaphragmatic
dysfunction may be the reason for the nocturnal respiratory events, particularly during REM sleep when the
physiological REM sleep-related muscle atonia is present, with diaphragmatic movements contributing the
bulk of the air exchange r18). Despite the fact that all
of our patients had a low Muller Pdi, not all of them
had a large number of diaphragmatic apneas and hypopneas during sleep, o r spent a large amount of sleep
time with an SaO, of less than 90%. The long periods
of time when SaO, was less than 90% in the 3 Group
B patients with existing daytime hypoventilation can
be explained by a combination of increased hypoventilation during sleep and sleep apneas. The fourth patient
(Patient 3) had predominantly REM-related apneas but
had a tendency to hypoventilate throughout sleep.
PFTs, performed during the daytime, were informative
and indicated those subjects who were more at risk of
having disordered breathing during sleep. O n the basis
of our study, the existence of a restrictive lung disease
and the presence of abnormal daytime blood gas levels
in the patients should raise the concern of a worsening
of breathing during sleep. We pointed out that restrictive lung disease was negatively correlated with disturbed breathing during sleep and with decreases in
SaO,. One may note that since the data are few, these
findings should be interpreted cautiously. We argue
that even though several observations are influential,
particularly those in Patients 5 and 12 (see Fig), results
were not markedly affected, and persistent negative
correlations were observed. Also, it is easy to understand why patients with M G who have a higher BMI
(i.e., higher loaded breathing and, more important,
chest bellow disease) will be at a higher risk of disordered breathing during sleep. However, one must emphasize that BMI was never massively elevated in our
patients. But a mild elevation of BMI may not be well
tolerated during sleep in older patients with MG. Age
is a variable that is not considered often enough as a
risk factor for abnormal breathing during sleep. The
majority of patients with M G who had a higher RDI
and RDI REM were older. Despite identification of
risk factors that appear to correlate with breathing disorders during sleep in our patients with MG, such as
abnormal PFI' results, abnormal daytime blood gas levels, elevated BMI, and older age (factors that have also
been found to be significant for predicting abnormal
breathing during sleep in other respiratory disorders
such as chronic obstructive pulmonary disease or myotonic dystrophy), we cannot explain in our population
the dichotomy in normal and abnormal breathing during sleep solely o n these daytime indices. For example,
Patient 12, 37 years old, with a TLC of 7 3 % ~of predicted value and a BMI of 17.5 (i.e., very slim), had
an RDI of 18, a REM sleep RDI of 85, and a percentage of time spent during sleep with an SaO, of less
than 90% of 13.3. She also had the highest amount of
REM sleep-related apnea.
In conclusion, patients with MG, even if appropriately treated during the daytime and possessing good
functional capacity and activity level, may have abnormal breathing during sleep. Sleep-related complaints
(disrupted nocturnal sleep, nocturnal awakening, and
so on) may allow us to suspect the problem. Older
patients with a moderate increase in BMI and abnormal
PFT results and daytime blood gas concentrations are
the primary candidates for sleep-disordered breathing
Ouera-Salva et al: Breathing Disorders during Sleep in MG
91
and oxygen desaturation during sleep. O n e issue that
was not addressed in this report, but which will be in
the second phase of this investigation, is the limited
duration of action of some of the treatments prescribed
for MG. Several prescribed drugs have too short a
half-life to maintain appropriate coverage throughout
the TST.
This study was supported by I'Association Frangaise contre les
Myopathies (AFM) an,J by the grant NS-07772 from the National
Insritute of Aging.
We are indebted to Daniele Morlat, Jean-Marc Sadriri, ant1 Gilles
Macadoux for their technical support, and Corine Redelsperger for
typing the manuscript.
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