Abnormal respiration and sudden death during sleep in multiple system atrophy with autonomic failure Frederick E. Munschauer, MD; Laurence Loh, MB, FFARCS; Roger Bannister, DM, FRCP; and John Newsom-DavisDM, FRCP
Article abstract-We studied respiration during sleep in 7 patients with multiple system atrophy and autonomic failure (MSA-AF) and 7 control subjects. Although mean respiratory rate, tidal volume, and inspiratory flow rate were statistically similar in both groups, the coefficients of variability in all were significantly greater in MSA-AF patients. Four of 5 nontracheostomized had evidence of upper airway obstruction without significant oxygen desaturation. Three of these 5 patients died suddenlyduring sleep. MSA-AF is associated with upper airway dysfunction and disordered central respirationswhich can be life threatening. Evidence of even mild obstruction during sleep should warrant tracheostomy. NEUROLOGY 1990;40:677-679
The control of respiration may be disordered in multiple system atrophy and autonomic failure (MSA-AF, Shy-Drager syndrome). Stridor during sleep has been well reported. In addition to upper airway obstruction, several authors have reported patients with irregular respiration suggestive of impaired central generation of respiratory rn~vements.'.~.~.~-~ To characterize the disorder in the control of ventilation, we studied respiration during sleep in 7 patients with MSA-AF and compared it with that of normals. Methods. Spontaneous ventilation during sleep was studied in 7 MSA-AF patients and compared with that of 7 healthy controls. All patients were referred to the National Hospital for Nervous Disease, Queen Square, London for evaluation of respiratory symptoms associated with MSA-AF (diagnosis confirmed by 1of the investigators-R.B.). Presenting respiratory symptoms ranged from inspiratory gasping during wakefulness to frank stridor during sleep. Two patients had stridor so severe that tracheostomywas required. When studied, all patients were free from acute systemic disease or metabolicdisturbances.The clinical featuresof these patients are summarized in table 1. Investigationswere carried out in the sleep study facility of the Batten Intensive Care Unit. Each subjectwas studied for a single night (8to 10 hours). EEG activity, extraocular movements, pharyngeal sounds, respiratory excursions, and transcutaneous oxygen were measured in all patients and controls. EEG activity was monitored with Cz to A1 and Cz to A2 leads. Ocular movementswere recordedby electrodesplaced over the lateral orbits and referenced to the midline. We recorded oral pharyngeal airway sounds using a microphone fixed to the lateral aspect of the throat. Most patients had a radial artery
cannula placed for the monitoring of blood pressure and arterial blood gases. Thoracic and abdominal respiratory movements were monitored by magnetometers calibrated by regression to pneumotachograph-derived flow and volume measurements. In all cases the regression converged and magnetometer-derived tidal volume measurements were within 10% of those measured by the pneumotachograph. An additional computational algorhythm calculated inspiratury time, expiratorytime, and derived an instantaneous respiratory frequency. Mean inspiratory flow rates were obtained for each breath by dividing the tidal volume by the inspiratory time (TV/Ti) on a breath by breath basis. At least 150 breaths (range, 153 to 894) from each patient and at least 100 breaths from each control were analyzed. Only breaths recorded while the patients were supine were analyzed. Means, standard deviations, and coefficients of variation (meanlstandard deviation) were calculated for all factors. A Wilkes-Shapiro test was applied to confirm that the data was normally distributed. When indicated, an unequal variance t test was used to compare patients and controls. Statistical significance was defined at p < 0.05. Central apnea was defined as a period of time where respiratory efforts were either absent or of such low amplitude as to produce a tidal volume of less than 50 cc. Obstructive apnea was easily appreciated by noting paradoxical movements of the thorax and abdomen during an inspiratory effort. Upper airway noises were usually maximal during the early and late phases of obstruction.
Results. None of the controls had breathingabnormalities during sleep. All MSA-AFpatients showed marked variation in tidal volumes. The variability occurred on a breath-to-breath basis rather than as populations of
From the State University of New York at Buffalo (Dr. Munschauer), Buflalo, NY, and The National Hospital for Nervous Disease (Drs. Loh, Bannister, and Newsom-Davis), Queen Square, London, UK. Received February 16,1988.Accepted for publication in final form September 25,1989. Address correspondence and reprint requwta to Dr. Frederick E. Munschauer, University of New York at Buflalo, Department of Neurology, BuEdo General Hospital, 100 High Street, Buffalo, NY 14203. April 1990 NEUROLOGY 40 677
Table 1. Summary of clinical data 1 Age/Sex
68/M
2
66/F
Duration of illness (yrs)
2
Respiratory symptoms Irregular breathing/ gasps while awake Loud snoring Vocal cord paralysis
+ +++ ++
Sleep Study Tracheostomy Stridor Central apnea 0, desaturation
-
-
Autonomic dysfunction Orthostasis Incontinence Impotency Sweating disturbance Motor dysfunction Pyramidal signs Extrapyramidal signs Cerebellar dysfunction
NE Not examined. N/A Not applicable. - Absent.
NEUROLOGY 40 April 1990
7
58/M
47/M
68/M
49/M
51/M
7
+ -
6
+ +++
4
5
++ ++ +
+ +
+
-
-
-
-
-
+
4
4
+++
++
NE
+++ ++
-
-
-
-
-
-
-
-
+ + + ++
+ + + +
++ +++
+ +++
+ ++
-
-
+ + +
+++ ++ + +
+++ + NIA +
+++ ++ ++ ++
++ ++ ++ +
+ + + ++
+ +++
+++ ++
+
-
-
++
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+
-
-
-
++ +++
+
-
++
+++
-
-
Mild signs or symptoms without dysfunction. Moderate: signs or symptoms with dysfunction Severe: disability.
breaths differing in tidal volumes. Single breaths of large tidal volumes were seen in MSA-AF patients. Apneustic or cluster breathing patterns did not occur. Loud snoring and stridorous sounds were frequently recorded, but only 1 patient had an episode of central apnea greater than 10 seconds. Clinically, irregular respiratory patterns were more pronounced in those patients with severe orthostasis. Patients with prominent extrapyramidalor cerebellar dysfunction but only mild orthostasis tended to have more regular patterns. There were no significant differences in respiratory rate, tidal volume, inspiratory flow rate, minute ventilation, or inspiratory time/respiratory cycle time (Ti/ Tot) between the patient and control groups. However, there were significant differences in the coefficients of variation of all these respiratory factors (table 2). Five of the 7 patients studied have subsequently died. In 2, the cause of death was not related to their neurologic illness (pneumonia, myocardial infarction). Three others died from cardiopulmonary arrest during sleep. Each of these 3 had highly variable tidal volumes and clinically evident obstruction during sleep without significant desaturation. Necropsy on 4 patients confirmed the diagnosis of MSA-AF. Extensive gliosis and neuronal loss in the medulla, pons, and substantia nigra was observed in 3. Only patient 4, a 47-year-old man with moderate auto678
6
+1-
-
+
5
NE
++
++ +++
Patient number 4
+
-
Sensory disturbances Painltemperature Vibration/proprioception Cognitive impairment
3
nomic and extrapyramidal signs, showed relatively little neuronal loss in the pontine tegmentum and medullary reticulum. This patient had desaturation in sleep of such a mild degree that a tracheostomy was not thought to be indicated.
Discussion. Upper airway obstruction clinically manifest as stridor during sleep is the most commonly observed respiratory abnormality in MSA-AF and may be life threatening. In a study of 12 consecutive patients with MSA-AF, Williams et all1 described 8 patients with excessive snoring, sleep apnea, or stridor. Respiration was felt to be sufficiently compromised to require tracheostomy in 4. Laryngoscopy in cases of MSA-AF with stridor has usually revealed either unilateral or bilateral cord adduction due to paresis of cord abductors. Selectiveatrophy of the posterior cricoarytenoidmuscles was shown at necropsy of 3 MSA-AF patients. Microscopically these vocal cord abductors showed extensive fiber size variation and tight grouping on histochemical staining. Laryngeal EMG has confirmed a selective neuropathy involving cord abductors.3 The etiology of this selective abductor paresis is unclear. Death of abductor neurons within the nucleus ambiguus has been considered,but careful examination of motor neurons in the nucleus ambiguus failed to show
Table 2. Coefficient of variability in respiratory mechanics Function Tidal volume (TV) Respiratory rate Inspiratory time (Ti) Expiratory time (Te) Mean imp. flow (TV/Ti)
Controls
Patients
17% 11% 14% 16% 18%
43% 35% 25% 42% 37%
p (0.05 p < 0.01 p < 0.02 p < 0.03 p < 0.02
neuronal loss or localized g l i ~ s i s . ~ Evidence for a more widespread disturbance in the central control of ventilation comes from the clinical observation of disordered patterns of ventilation during wakefulness in MSA-AF. Most commonly noted are involuntary inspiratory gasps characterized by a large brief inspiratory effort of shorter duration than apneustic breaths. Chokroverty et als described dysrhythmic breathing characterized by recurrent central apnea and ineffective ventilation in the absence of stridor in 4 MSA-AF patients. Disorders of respiration in MSA-AF patients are most apparent during sleep when ventilation is not under voluntary control. McNicholas et als noted that the coefficient of variation in instantaneous minute ventilation, TV/Ti, and Ti/Tot during sleep were 2 to 3 times greater than normal in MSA-AF patients. While awake, the MSA-AFpatients had no difficulty reproducing target tidal volumes indicating intact respiratory proprioception. The results of our study are similar to those of McNicholas et al. MSA-AF patients generated highly irregular tidal volumes during deep sleep when respiratory rhythms are characteristically regular. Further, tidal volumes varied on a breath-by-breath basis rather than as periods of hyper- or hypoventilation. Minute ventilations were normal, implying normal CO, chemoreceptors. Brainstem pathways subserving the generation of respirations are thought to arise from medullarycenters while higher centers influence rhythmicity. Evidence from both experimentalstudies and human case reports indicate that neurons adjacent to the nucleus and tractus solitarius, termed the dorsal respiratory group (DRG), may generate the graded inspiratory activity of respirations.1° Bilateral lesions of the pontine tegmentum caudal to the motor trigeminal nuclei or bilateral lesions of the lateral pontomedullaryjunction may produce dysrhythmic respirations. Pontine tegmental lesions, however, characteristically produce markedly abnormal respiratory patterns including sustained inspiratory and expiratory tonic activity or cluster breathing. Such patterns were not observed in our patients with MSA-AF. All but 1of our autopsied patients (patient 4) had marked neuronal loss in the region of the pontine tegmentum and medullary reticular formation, including
neurons normally found around the tractus solitarius. We are unable to localize more precisely the lesion responsible for the variability in measured respiratory factors. The variability in tidal volumes without significant aberration in minute ventilation seen in our patients, however, suggests dysfunction of the rhythmic modulation of inspiratory activity within the medullary DRG. Three of our patients (43%) subsequently died suddenly during sleep without prodrome of overt cardiorespiratory dysfunction. During our sleep studies,only 1of these sudden-death patients showed desaturation; the degree of desaturation was not considered sufficient to warrant tracheostomy. Sudden death during sleep may occur because MSAAF patients have little or no increase in minute ventilation with hypoxia? An intact hypoxic ventilatory response may be crucial in the setting of even moderate obstruction for arousal and subsequent voluntary augmentation of ventilation. Accordingly, MSA-AF patients may be at significantly greater risk for a catastrophic desaturation during sleep. Laryngoscopy to screen for unilateral or bilateral cord paralysis should be performed in MSA-AF patients who present with changes in voice, snoring, or inspiratory gasping. Disordered central generation of respiration and blunted hypoxic drive in MSA-AF may render even mild obstruction life threatening. In MSA-AF the presence of mild obstruction during sleep should prompt early tracheostomy.
References 1. Bannister R, OppenheimerDR. Degenerative diseaees of the nervous system associated with autonomic failure. Brain 1972;95457-474. 2. Spokes EG, Bannister R, OppenheimerDR. Multiple system atrophy with autonomic failure. J Neurol Sci 1979;4359-82. 3. Guindi GM, Bannister R, Gibson WP, et al. Laryngeal electromyographyin multiple system atrophywith autonomic failure. J Neurol Neurosurg Psychiatry 1981;4449-53. 4. Bannister R, Gibson W, Michaels L, et al. Laryngeal abductor paralysis in multiple system atrophy. Brain 1981;104351-368. 5. Lockwood AH. Shy-Dragersyndromewith abnormal respirations and antidiuretic hormone release. Arch Neurol 1975;33:292-295. 6. Chokroverty S, Sharp JT, Barron KD. Periodic respiration in erect posture in Shy-Drager syndrome. J N e w 1 Neurosurg Psychiatry 1978;41:980-986. 7. Kenyon GS, Apps MCP, Traub M. Stridor and obstructive sleep apnea in Shy-Dragersyndrome treated by laryngofissure and cord lateralization. Laryngoscope 19&1,941106-1108. 8. Apps MCP, Sheaff PC, Ingram DA, et al. Respirationand sleep in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1985,481240-1245. 9. McNicholw WT, Rutherford R, Grossman R, et al. Abnormal respiratorypattern generation during sleep in patienta with autonomic dysfunction. Am Rev Respir Die 1983;128429-433. 10. von Euler C. On the central pattern generator for the basic breathing rhythmicity. J Appl Physiol: Resp Environ Exerck Phyaiol1983;551647-1659. 11. WilliamsA,HaneonD,CalneDB.VocalconlparalysisintheShyDrager syndrome. J Neurol Neurosurg Psychiatry 1979;42:151-153.
April 1990 NEUROLOGY 40 679
Abnormal respiration and sudden death during sleep in multiple system atrophy with autonomie failure Frederick E. Munschauer, Laurence Loh, Roger Bannister, et al. Neurology 1990;40;677 DOI 10.1212/WNL.40.4.677 This information is current as of April 1, 1990 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/40/4/677.full.html
Citations
This article has been cited by 10 HighWire-hosted articles: http://www.neurology.org/content/40/4/677.full.html##otherarticle s
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1990 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
Article abstract-We studied respiration during sleep in 7 patients with multiple system atrophy and autonomic failure (MSA-AF) and 7 control subjects. Although mean respiratory rate, tidal volume, and inspiratory flow rate were statistically similar in both groups, the coefficients of variability in all were significantly greater in MSA-AF patients. Four of 5 nontracheostomized had evidence of upper airway obstruction without significant oxygen desaturation. Three of these 5 patients died suddenlyduring sleep. MSA-AF is associated with upper airway dysfunction and disordered central respirationswhich can be life threatening. Evidence of even mild obstruction during sleep should warrant tracheostomy. NEUROLOGY 1990;40:677-679
The control of respiration may be disordered in multiple system atrophy and autonomic failure (MSA-AF, Shy-Drager syndrome). Stridor during sleep has been well reported. In addition to upper airway obstruction, several authors have reported patients with irregular respiration suggestive of impaired central generation of respiratory rn~vements.'.~.~.~-~ To characterize the disorder in the control of ventilation, we studied respiration during sleep in 7 patients with MSA-AF and compared it with that of normals. Methods. Spontaneous ventilation during sleep was studied in 7 MSA-AF patients and compared with that of 7 healthy controls. All patients were referred to the National Hospital for Nervous Disease, Queen Square, London for evaluation of respiratory symptoms associated with MSA-AF (diagnosis confirmed by 1of the investigators-R.B.). Presenting respiratory symptoms ranged from inspiratory gasping during wakefulness to frank stridor during sleep. Two patients had stridor so severe that tracheostomywas required. When studied, all patients were free from acute systemic disease or metabolicdisturbances.The clinical featuresof these patients are summarized in table 1. Investigationswere carried out in the sleep study facility of the Batten Intensive Care Unit. Each subjectwas studied for a single night (8to 10 hours). EEG activity, extraocular movements, pharyngeal sounds, respiratory excursions, and transcutaneous oxygen were measured in all patients and controls. EEG activity was monitored with Cz to A1 and Cz to A2 leads. Ocular movementswere recordedby electrodesplaced over the lateral orbits and referenced to the midline. We recorded oral pharyngeal airway sounds using a microphone fixed to the lateral aspect of the throat. Most patients had a radial artery
cannula placed for the monitoring of blood pressure and arterial blood gases. Thoracic and abdominal respiratory movements were monitored by magnetometers calibrated by regression to pneumotachograph-derived flow and volume measurements. In all cases the regression converged and magnetometer-derived tidal volume measurements were within 10% of those measured by the pneumotachograph. An additional computational algorhythm calculated inspiratury time, expiratorytime, and derived an instantaneous respiratory frequency. Mean inspiratory flow rates were obtained for each breath by dividing the tidal volume by the inspiratory time (TV/Ti) on a breath by breath basis. At least 150 breaths (range, 153 to 894) from each patient and at least 100 breaths from each control were analyzed. Only breaths recorded while the patients were supine were analyzed. Means, standard deviations, and coefficients of variation (meanlstandard deviation) were calculated for all factors. A Wilkes-Shapiro test was applied to confirm that the data was normally distributed. When indicated, an unequal variance t test was used to compare patients and controls. Statistical significance was defined at p < 0.05. Central apnea was defined as a period of time where respiratory efforts were either absent or of such low amplitude as to produce a tidal volume of less than 50 cc. Obstructive apnea was easily appreciated by noting paradoxical movements of the thorax and abdomen during an inspiratory effort. Upper airway noises were usually maximal during the early and late phases of obstruction.
Results. None of the controls had breathingabnormalities during sleep. All MSA-AFpatients showed marked variation in tidal volumes. The variability occurred on a breath-to-breath basis rather than as populations of
From the State University of New York at Buffalo (Dr. Munschauer), Buflalo, NY, and The National Hospital for Nervous Disease (Drs. Loh, Bannister, and Newsom-Davis), Queen Square, London, UK. Received February 16,1988.Accepted for publication in final form September 25,1989. Address correspondence and reprint requwta to Dr. Frederick E. Munschauer, University of New York at Buflalo, Department of Neurology, BuEdo General Hospital, 100 High Street, Buffalo, NY 14203. April 1990 NEUROLOGY 40 677
Table 1. Summary of clinical data 1 Age/Sex
68/M
2
66/F
Duration of illness (yrs)
2
Respiratory symptoms Irregular breathing/ gasps while awake Loud snoring Vocal cord paralysis
+ +++ ++
Sleep Study Tracheostomy Stridor Central apnea 0, desaturation
-
-
Autonomic dysfunction Orthostasis Incontinence Impotency Sweating disturbance Motor dysfunction Pyramidal signs Extrapyramidal signs Cerebellar dysfunction
NE Not examined. N/A Not applicable. - Absent.
NEUROLOGY 40 April 1990
7
58/M
47/M
68/M
49/M
51/M
7
+ -
6
+ +++
4
5
++ ++ +
+ +
+
-
-
-
-
-
+
4
4
+++
++
NE
+++ ++
-
-
-
-
-
-
-
-
+ + + ++
+ + + +
++ +++
+ +++
+ ++
-
-
+ + +
+++ ++ + +
+++ + NIA +
+++ ++ ++ ++
++ ++ ++ +
+ + + ++
+ +++
+++ ++
+
-
-
++
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+
-
-
-
++ +++
+
-
++
+++
-
-
Mild signs or symptoms without dysfunction. Moderate: signs or symptoms with dysfunction Severe: disability.
breaths differing in tidal volumes. Single breaths of large tidal volumes were seen in MSA-AF patients. Apneustic or cluster breathing patterns did not occur. Loud snoring and stridorous sounds were frequently recorded, but only 1 patient had an episode of central apnea greater than 10 seconds. Clinically, irregular respiratory patterns were more pronounced in those patients with severe orthostasis. Patients with prominent extrapyramidalor cerebellar dysfunction but only mild orthostasis tended to have more regular patterns. There were no significant differences in respiratory rate, tidal volume, inspiratory flow rate, minute ventilation, or inspiratory time/respiratory cycle time (Ti/ Tot) between the patient and control groups. However, there were significant differences in the coefficients of variation of all these respiratory factors (table 2). Five of the 7 patients studied have subsequently died. In 2, the cause of death was not related to their neurologic illness (pneumonia, myocardial infarction). Three others died from cardiopulmonary arrest during sleep. Each of these 3 had highly variable tidal volumes and clinically evident obstruction during sleep without significant desaturation. Necropsy on 4 patients confirmed the diagnosis of MSA-AF. Extensive gliosis and neuronal loss in the medulla, pons, and substantia nigra was observed in 3. Only patient 4, a 47-year-old man with moderate auto678
6
+1-
-
+
5
NE
++
++ +++
Patient number 4
+
-
Sensory disturbances Painltemperature Vibration/proprioception Cognitive impairment
3
nomic and extrapyramidal signs, showed relatively little neuronal loss in the pontine tegmentum and medullary reticulum. This patient had desaturation in sleep of such a mild degree that a tracheostomy was not thought to be indicated.
Discussion. Upper airway obstruction clinically manifest as stridor during sleep is the most commonly observed respiratory abnormality in MSA-AF and may be life threatening. In a study of 12 consecutive patients with MSA-AF, Williams et all1 described 8 patients with excessive snoring, sleep apnea, or stridor. Respiration was felt to be sufficiently compromised to require tracheostomy in 4. Laryngoscopy in cases of MSA-AF with stridor has usually revealed either unilateral or bilateral cord adduction due to paresis of cord abductors. Selectiveatrophy of the posterior cricoarytenoidmuscles was shown at necropsy of 3 MSA-AF patients. Microscopically these vocal cord abductors showed extensive fiber size variation and tight grouping on histochemical staining. Laryngeal EMG has confirmed a selective neuropathy involving cord abductors.3 The etiology of this selective abductor paresis is unclear. Death of abductor neurons within the nucleus ambiguus has been considered,but careful examination of motor neurons in the nucleus ambiguus failed to show
Table 2. Coefficient of variability in respiratory mechanics Function Tidal volume (TV) Respiratory rate Inspiratory time (Ti) Expiratory time (Te) Mean imp. flow (TV/Ti)
Controls
Patients
17% 11% 14% 16% 18%
43% 35% 25% 42% 37%
p (0.05 p < 0.01 p < 0.02 p < 0.03 p < 0.02
neuronal loss or localized g l i ~ s i s . ~ Evidence for a more widespread disturbance in the central control of ventilation comes from the clinical observation of disordered patterns of ventilation during wakefulness in MSA-AF. Most commonly noted are involuntary inspiratory gasps characterized by a large brief inspiratory effort of shorter duration than apneustic breaths. Chokroverty et als described dysrhythmic breathing characterized by recurrent central apnea and ineffective ventilation in the absence of stridor in 4 MSA-AF patients. Disorders of respiration in MSA-AF patients are most apparent during sleep when ventilation is not under voluntary control. McNicholas et als noted that the coefficient of variation in instantaneous minute ventilation, TV/Ti, and Ti/Tot during sleep were 2 to 3 times greater than normal in MSA-AF patients. While awake, the MSA-AFpatients had no difficulty reproducing target tidal volumes indicating intact respiratory proprioception. The results of our study are similar to those of McNicholas et al. MSA-AF patients generated highly irregular tidal volumes during deep sleep when respiratory rhythms are characteristically regular. Further, tidal volumes varied on a breath-by-breath basis rather than as periods of hyper- or hypoventilation. Minute ventilations were normal, implying normal CO, chemoreceptors. Brainstem pathways subserving the generation of respirations are thought to arise from medullarycenters while higher centers influence rhythmicity. Evidence from both experimentalstudies and human case reports indicate that neurons adjacent to the nucleus and tractus solitarius, termed the dorsal respiratory group (DRG), may generate the graded inspiratory activity of respirations.1° Bilateral lesions of the pontine tegmentum caudal to the motor trigeminal nuclei or bilateral lesions of the lateral pontomedullaryjunction may produce dysrhythmic respirations. Pontine tegmental lesions, however, characteristically produce markedly abnormal respiratory patterns including sustained inspiratory and expiratory tonic activity or cluster breathing. Such patterns were not observed in our patients with MSA-AF. All but 1of our autopsied patients (patient 4) had marked neuronal loss in the region of the pontine tegmentum and medullary reticular formation, including
neurons normally found around the tractus solitarius. We are unable to localize more precisely the lesion responsible for the variability in measured respiratory factors. The variability in tidal volumes without significant aberration in minute ventilation seen in our patients, however, suggests dysfunction of the rhythmic modulation of inspiratory activity within the medullary DRG. Three of our patients (43%) subsequently died suddenly during sleep without prodrome of overt cardiorespiratory dysfunction. During our sleep studies,only 1of these sudden-death patients showed desaturation; the degree of desaturation was not considered sufficient to warrant tracheostomy. Sudden death during sleep may occur because MSAAF patients have little or no increase in minute ventilation with hypoxia? An intact hypoxic ventilatory response may be crucial in the setting of even moderate obstruction for arousal and subsequent voluntary augmentation of ventilation. Accordingly, MSA-AF patients may be at significantly greater risk for a catastrophic desaturation during sleep. Laryngoscopy to screen for unilateral or bilateral cord paralysis should be performed in MSA-AF patients who present with changes in voice, snoring, or inspiratory gasping. Disordered central generation of respiration and blunted hypoxic drive in MSA-AF may render even mild obstruction life threatening. In MSA-AF the presence of mild obstruction during sleep should prompt early tracheostomy.
References 1. Bannister R, OppenheimerDR. Degenerative diseaees of the nervous system associated with autonomic failure. Brain 1972;95457-474. 2. Spokes EG, Bannister R, OppenheimerDR. Multiple system atrophy with autonomic failure. J Neurol Sci 1979;4359-82. 3. Guindi GM, Bannister R, Gibson WP, et al. Laryngeal electromyographyin multiple system atrophywith autonomic failure. J Neurol Neurosurg Psychiatry 1981;4449-53. 4. Bannister R, Gibson W, Michaels L, et al. Laryngeal abductor paralysis in multiple system atrophy. Brain 1981;104351-368. 5. Lockwood AH. Shy-Dragersyndromewith abnormal respirations and antidiuretic hormone release. Arch Neurol 1975;33:292-295. 6. Chokroverty S, Sharp JT, Barron KD. Periodic respiration in erect posture in Shy-Drager syndrome. J N e w 1 Neurosurg Psychiatry 1978;41:980-986. 7. Kenyon GS, Apps MCP, Traub M. Stridor and obstructive sleep apnea in Shy-Dragersyndrome treated by laryngofissure and cord lateralization. Laryngoscope 19&1,941106-1108. 8. Apps MCP, Sheaff PC, Ingram DA, et al. Respirationand sleep in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1985,481240-1245. 9. McNicholw WT, Rutherford R, Grossman R, et al. Abnormal respiratorypattern generation during sleep in patienta with autonomic dysfunction. Am Rev Respir Die 1983;128429-433. 10. von Euler C. On the central pattern generator for the basic breathing rhythmicity. J Appl Physiol: Resp Environ Exerck Phyaiol1983;551647-1659. 11. WilliamsA,HaneonD,CalneDB.VocalconlparalysisintheShyDrager syndrome. J Neurol Neurosurg Psychiatry 1979;42:151-153.
April 1990 NEUROLOGY 40 679
Abnormal respiration and sudden death during sleep in multiple system atrophy with autonomie failure Frederick E. Munschauer, Laurence Loh, Roger Bannister, et al. Neurology 1990;40;677 DOI 10.1212/WNL.40.4.677 This information is current as of April 1, 1990 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/40/4/677.full.html
Citations
This article has been cited by 10 HighWire-hosted articles: http://www.neurology.org/content/40/4/677.full.html##otherarticle s
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1990 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
