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Rapidly progressive fatal respiratory failure (Ondine’s curse) in the lateral medullary syndrome
Case Report
Rapidly Progressive Fatal Respiratory Failure (Ondine’s Curse) in the Lateral Medullary Syndrome Shin-ichi Terao, MD,* Naofumi Miura, MD,* Yutaka Osano, Aiji Noda, MD,* and Gen Sobue, MD†
MD,*
A 70-year-old man presented with unilateral lateral medullary infarction, and then died of rapidly progressive respiratory failure within a day. The clinical manifestations were hiccups, hoarseness, dysarthria, nystagmus, left central facial paralysis, paralysis of the left soft palate, dysphagia, decreased superficial sensation over the right face and upper limb, and cerebellar ataxia in the left upper and lower limbs. The arterial blood gas analysis revealed mild hypoventilation. Soon thereafter, an apneic episode occurred during a sleep and advanced to ataxic respiration, and the patient Died. Pathologically, there were fresh ischemic infarction localized to the left dorsolateral area of the upper medulla, caused by atherothrombotic occlusion of the left vertebral artery. These foci were in the areas including the medullary reticular formation, the solitary nucleus, the intramedullary fibers of the vagus nerve, and the nucleus ambiguus on the left side. We attributed the fatal acute progressive respiratory impairment in the present case to impairment of the automatic respiratory system (Ondine’s curse) rather than the voluntary respiratory system. Key Words: Lateral medullary syndrome—medullary infarction— medullary reticular formation—respiratory failure. © 2004 by National Stroke Association
The human central respiratory control depends on numerous neurological structures, extending from the cerebral cortex to the medulla oblongata. Respiration depends on parallel systems mediating the voluntary, automatic, and limbic control of breathing. These different pathways appear to converge at the spinal cord level.1-3 The respiratory centers are mainly distributed
From the Division of General Medicine, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan, and the †Department of Neurology, Nagoya University School of Medicine, Nagoya, Japan. Received June 23, 2003; accepted September 19, 2003. Address reprint requests to Shin-ichi Terao, MD, Division of General Medicine, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi 480-1195, Japan. E-mail: [email protected] 1052-3057/$—see front matter © 2004 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2003.11.026
from the pons to the medulla, while the neural organization of which has not been sufficiently elucidated.1-3 In the acute phase of cerebrovascular diseases, central respiratory abnormalities such as Cheyne-Stokes respiration, central hyperventilation, sleep apnea, automatic breathing impairment, and ataxic breathing are seen.3,4 In general, the functional prognosis of the lateral medullary syndrome (LMS) is good, although a poor outcome was reported in some cases.5,6 We report herein a case of unilateral LMS that rapidly progressed to fatal respiratory failure with autopsy findings.
Case Report A 70-year-old man was referred to our hospital with nausea and vomiting, and unsteadiness while walking. He had a history of duodenal ulcer 30 years ago, but there was no history of hypertension, diabetes, hyperlipidemia,
Journal of Stroke and Cerebrovascular Diseases, Vol. 13, No. 1 (January-February), 2004: pp 41-44
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or smoking. On the afternoon of the day before his hospitalization, he experienced a sudden onset of hidrosis on the head, a floating sensation, and difficulty in speaking, all of which resolved in 30 minutes. Soon thereafter, he started to deviate to the left side when he walked. Subsequently, he had two episodes of vomiting, but was able to take meals. He also had dull pain in the left occipital region. At the time of hospitalization he was lucid, with no evident intellectual impairment. His blood pressure was 200/130 mm Hg, pulse 80 beats per minute with no arrhythmia, and respiratory rate 17 breaths per minute. His height was 154 cm, he weighed 60 kg, and had a body temperature of 35.9°C. No bruit was heard in the neck. Neurologically, there were hoarseness, dysarthria, horizontal and rotatory nystagmus to the right gaze, the left central facial paralysis, the paralysis of the left soft palate, continuing hiccups, and dysphagia. No pupillary abnormalities, including Homer syndrome, were detected. There was no motor paralysis in the tongue or limbs. Decreased superficial sensation on the right face and upper limb was present. There was no abnormality in the deep sensations. The deep tendon reflexes were generally decreased. Babinski’s sign was not present. Cerebellar ataxia in the left upper and lower limbs was present. The blood gas analysis results were pH 7.42 in room air, PaO2 61.3 mm Hg, PaCO2 47.2 mm Hg, HCO3 29.7 mEq/1, and SaO2 92.5%, suggesting mildly impaired lung ventilation. Mild dehydration was suggested by the peripheral blood and biochemical tests. There were no abnormalities in the chest radiography, while electrocardiography showed mild hypertensive changes. There were no evident brain lesions on plain computed tomography. At this time, an ischemic lesion was suggested in the left dorsolateral portion of the medulla oblongata. Oxygen was administered at a dose of 1 1/min, and the patient was managed with hydration. The nausea, hiccups, and headache disappeared. At night 6 hours after admission (9:00 p.m.), his respiratory rate was regular at 30 to 35 breaths per minute when he was lucid, but during sleep, frequent apnea episodes of 5 to 10 seconds were noticed. There was no paralysis of the tongue, his blood pressure was 198/118 mm Hg, and his pulse was 100 to 110 beats per minute. Eleven hours after admission (2:00 a.m.), he was alert and responded well to the verbal orders. Saliva and sputum accumulated in his mouth, so frequent aspiration was performed. Sudden ataxic respiration appeared with the patient in a somnolent state one hour later (3:00 a.m.), and he died in the next hour. Continuous electrocardiography monitoring was conducted during hospitalization and there was no arrhythmia, ischemic changes, or any feature of heart failure. An endotracheal tube with mechanical ventilation was not placed. The scheduled head magnetic resonance imaging and cerebral angiography were not carried out.
Figure 1. Gross pathological findings of the cerebral arteries. The main arteries are showed: vertebral artery (VA), basilar artery (BA), posterior inferior cerebellar artery (PICA), anterior inferior cerebellar artery (AICA), superior cerebellar artery (SCA), middle cerebral artery (MCA), anterior cerebral artery (ACA).
Autopsy of the brain was subsequently performed. On gross examination, an atherothrombotic occlusion of the left vertebral artery was confirmed. The left posterior inferior cerebellar artery was not identified. The right posterior inferior cerebellar artery branched from the right vertebral artery, and the left anterior inferior cerebellar artery branched from the basilar artery (Fig 1). Histologically, there were fresh ischemic infarction localized to the left dorsolateral medulla, including the medullary reticular formation, the solitary nucleus, the intramedullary fibers of the vagus nerve, the nucleus ambiguus, and the spinal tract of the trigeminal nerve. In these regions, there were mild edema and pallor of Klu¨ ver-Barrera stain (Fig 2), dark staining and atrophy of the neurons, cells exhibiting eosinophilic ischemic changes, perivascular neutrophil and macrophage invasion, vacuolar degeneration, and axonal swelling around the malacia lesions. In addition, there was hypertrophy of the intima in the vertebral artery, basilar aretry, internal carotid artery, and middle cerebral artery. Occlusion of these arteries were not present.
Discussion This patient began clinically with typical left LMS, but within 24 hours, he progressed rapidly to show central
RESPIRATORY FAILURE IN LATERAL MEDULLARY SYNDROME
43
Figure 2. Histopathological transverse section at the level of the upper medulla (A). Klu¨ ver-Barrera stain ⫻ 7. The dorsolateral portion shows pallor (arrow). The right schema shows the neural architecture in the medulla oblongata (B). The location of key structures are marked: corticospinal tract (1); medial lemniscus (2); medial longitudinal fasciculus (3); hypoglossal nerve (XII) (4); hypoglossal nucleus (5); inferior olivary nucleus (6); spinothalamic tract (7); nucleus ambiguus (8); solitary nucleus (9); descending sympathetic tract (10); vagus nerve (X) (11); descending trigeminal tract (12); ascending trigeminal thalamic tract (13); inferior cerebellar peduncle (14); vestibular nucleus (15); dorsal nucleus of vagus (16); medullary reticular formation (17).
apnea, followed by ataxic respiration and, finally, respiratory failure leading to death. Symptomatologically, left central facial paralysis was observed in our patient. We studied to clarify the course of the facial corticobulbar tract in a large group of patients with lower brain stem infarction. We previously reported that the facial corticobulbar tract fibers descend at the ventromedial lower pons, near the corticospinal tract, mainly to the level of the upper medulla, where the fibers then decussate and ascend in the dorsolateral medulla to synapse in the contralateral facial nucleus.18,19 Ipsilateral central facial paralysis in the patient may have resulted from involvement to these ascending fibers. Decreased superficial sensation of right face was compatible with involvement to the ascending trigeminal thalamic tract in the left lateral medulla. Furthermore, decreased sensation of right upper limb was caused by the partial involvement of the spinothalamic tract.20 In our patient, no pupil abnormlities, including Horner syndrome, were detected. It may be spared the involvement of the descending central sympathetic tract in the lateral part of medulla (Fig 2).2 The respiratory functions including the voluntary, limbic, automatic, and reflex respirations relate to a multitude of structures extending from the cerebral cortex to the pontomedullary nuclei.2-4 The voluntary respiration is the system by which voluntary breathing movements are made during vigilance. The voluntary control origi-
nates at the cortical level, and its efferents appear to travel in the corticospinal tract.3,7 Automatic respiration, on the other hand, mainly regulates breathing automatically in response to the changes in oxygen and carbon dioxide in the blood, and changes in the movement of the lungs and thoracic cavity. Two centers are known to contribute to automatic respiration: the dorsal respiratory center in the ventrolateral part of the medullary solitary nucleus,1,3,4 and the ventral respiratory center, including the nucleus ambiguus, the dorsal nucleus of the vagus nerve, and the medullary reticular formation extending from the lower brainstem to the upper cervical cord.1,3 In the present case, there were neither abnormalities in the lungs, trachea, or thorax, nor neuromuscular diseases with impairment of the respiratory muscles. There was no motor paralysis of the limbs, and he could perform voluntary respiration in the alert state, indicating that the voluntary system was maintained. When he was lucid, however, he was in a hyperventilatory state. However, when he fell asleep or when his consciousness became impaired because of the accumulation of carbon dioxide, he progressively developed apnea or ataxic respiration. Taken together, it is presumed that impairment of the automatic respiration (Ondine’s curse)3,4,9,10 mainly occurred in the course of LMS and rapidly progressed to fatal respiratory failure. Several pathological investigations of LMS presenting as central apnea have been reported.7,8,10,11 Bogous-
S. TERAO ET AL.
44
slavsky et al8 reported that the automatic respiration was impaired by damage to the pontomedullary reticular formation and nucleus ambiguus, and that with a lesion of the solitary nucleus as well the voluntary respiration may also be affected. In contrast, Takehara et al11 reported that even if solitary nucleus impairment was present in addition to reticular formation and nucleus ambiguus disorders in LMS, only automatic respiratory disorder occurred; and there was no damage to the voluntary respiration. Our patient seemed to be similar to this latter report. Poor outcome in lateral medullary infarction patients can be caused by cerebellar infarction, dysphagia, abnormality of autonomic function or respiration, or a vascular occlusive lesion that causes progressive ischemia.5 Strokes complicated by Ondine’s curse usually result from a distal vertebral artery occlusion. When respiratory monitoring is performed, central respiratory abnormalities such as sleep apnea can be detected in LMS.12-14 The development of Ondine’s curse is a major determinant for poor outcome in this kind of stroke.5,6 The majority of reported clinicopathological studies describe patients with unilateral lateral medullary infarction.7,8 A leftsided predominance may be proposed for central control of respiration function.3 After crossing at the medullary level, the efferent fibers from the respiratory centers descend on both sides of the spinal cord, and thus a unilateral medullary lesion may affect the efferent pathways on both sides, and functionally impair respiration.8 Moreover, it has recently been pointed out that ischemia of the solitary nucleus in LMS may induce cardiopulmonary arrest in the acute stage.15,16 If LMS is suspected, one should take into account not only peripheral respiratory impairment such as aspiration,17 but also the possibility of the central, fatal impairment of apnea or ataxic respiration. Careful management with cardiopulmonary monitoring is particularly important in the acute stage of LMS. Acknowledgment: We are grateful to M. Yoshida, MD (Institute for Medical Science of Aging, Aichi Medical University School of Medicine) for the pathological comments.
References 1. Berger AJ, Mitchell RA, Severinghaus JW. Regulation of respiration: Second of three parts. N Engl J Med 1977; 297:138-143. 2. Plum F. Breathing is controlled independently by voluntary, emotional, and metabolically related pathways. Arch Neurol 1992;49:441.
3. Vingerhoets F, Bogousslavsky J. Respiratory dysfunction, In: Bogousslavsky J, Caplan LR (eds): Stroke syndromes. 2nd ed. Cambridge, MA, Cambridge University Press, 2001, 353-362. 4. Bassetti C, Aldrich MS, Quint D. Sleep-disordered breathing in patients with acute supra- and infratentorial strokes. A prospective study of 39 patients. Stroke 1997; 28:1765-1772. 5. Caplan LR, Pessin MS, Scott RM, et al. Poor outcome after lateral medullary infarcts. Neurology 1986;36:15101513. 6. Norrving B, Cronqvist S. Lateral medulary infarction: Prognosis in an unselected series. Neurology 1991;41: 244-248. 7. Levine BE, Margolis G. Acute failure of autonomic respirations secondary to a unilateral brainstem infarct. Ann Neurol 1977;1:583-586. 8. Bogousslavsky J, Khurana R, Deruaz JP, et al. Respiratory failure and unilateral caudal brainstem infarction. Ann Neurol 1990;28:668-673. 9. Severinghaus JW, Mitchel RA. Ondine’s curse—Failure of respiratory center automaticity while awake. Clin Res 1962;10:122. 10. Devereaux MW, Keane JR, Davis RL. Autonomic respiratory failure associated with infarction of the medulla. Report of two cases with pathologic study of one. Arch Neurol 1973;29:46-52. 11. Takehara M, Ishikawa K, Hiroi T, et al. Central type of sleep apnea syndrome caused by unilateral lateral medullary infarction. Rinsho Shinkeigaku 1992;32:511-515. 12. Askenacy JJM, Goldhammer I. Sleep apnea as a feature of bulbar stroke. Stroke 1988;19:637-639. 13. Good DC, Henkle JQ, Gelber D, et al. Sleep-disordered breathing and poor functional outcome after stroke. Stroke 1996;27:252-259. 14. Morrell MJ, Heywood P, Moosavi SH, et al. Unilateral focal lesions in the rostrolateral medulla influence chemosensitivity and breathing measured during wakefulness, sleep, and exercise. J Neurol Neurosurg Psychiatry 1999;67:637-645. 15. Caro RD, Parenti A, Montisci M, et al. Solitary tract nuclei in acute heart failure. Stroke 2000;31:1187-1193. 16. Jaster JH. Unexpected sudden death after lateral medullary infarction. J Neurol Neurosurg Psychiatry 2001;70: 137. 17. Kim H, Chung CS, Lee KH, et al. Aspiration subsequent to a pure medullary infarction. Lesion sites, clinical variables, and outcome. Arch Neurol 2000;57:478-483. 18. Terao S, Takatsu S, Izumi M, et al. Central facial weakness due to medial medullary infarction: The course of facial corticobulbar fibres. J Neurol Neurosurg Psychiatry 1997;63:391-393. 19. Terao S, Miura N, Takahashi A, et al. Course and distribution of facial corticobulbar tract fibres in the lower brain stem. J Neurol Neurosurg Psychiatry 2000;69:262265. 20. Kim JS. Pure lateral medullary infarction; clinical-radiological correlation of 130 acute, consecutive patients. Brain 2003;126:1864-1872.
Rapidly Progressive Fatal Respiratory Failure (Ondine’s Curse) in the Lateral Medullary Syndrome Shin-ichi Terao, MD,* Naofumi Miura, MD,* Yutaka Osano, Aiji Noda, MD,* and Gen Sobue, MD†
MD,*
A 70-year-old man presented with unilateral lateral medullary infarction, and then died of rapidly progressive respiratory failure within a day. The clinical manifestations were hiccups, hoarseness, dysarthria, nystagmus, left central facial paralysis, paralysis of the left soft palate, dysphagia, decreased superficial sensation over the right face and upper limb, and cerebellar ataxia in the left upper and lower limbs. The arterial blood gas analysis revealed mild hypoventilation. Soon thereafter, an apneic episode occurred during a sleep and advanced to ataxic respiration, and the patient Died. Pathologically, there were fresh ischemic infarction localized to the left dorsolateral area of the upper medulla, caused by atherothrombotic occlusion of the left vertebral artery. These foci were in the areas including the medullary reticular formation, the solitary nucleus, the intramedullary fibers of the vagus nerve, and the nucleus ambiguus on the left side. We attributed the fatal acute progressive respiratory impairment in the present case to impairment of the automatic respiratory system (Ondine’s curse) rather than the voluntary respiratory system. Key Words: Lateral medullary syndrome—medullary infarction— medullary reticular formation—respiratory failure. © 2004 by National Stroke Association
The human central respiratory control depends on numerous neurological structures, extending from the cerebral cortex to the medulla oblongata. Respiration depends on parallel systems mediating the voluntary, automatic, and limbic control of breathing. These different pathways appear to converge at the spinal cord level.1-3 The respiratory centers are mainly distributed
From the Division of General Medicine, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan, and the †Department of Neurology, Nagoya University School of Medicine, Nagoya, Japan. Received June 23, 2003; accepted September 19, 2003. Address reprint requests to Shin-ichi Terao, MD, Division of General Medicine, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi 480-1195, Japan. E-mail: [email protected] 1052-3057/$—see front matter © 2004 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2003.11.026
from the pons to the medulla, while the neural organization of which has not been sufficiently elucidated.1-3 In the acute phase of cerebrovascular diseases, central respiratory abnormalities such as Cheyne-Stokes respiration, central hyperventilation, sleep apnea, automatic breathing impairment, and ataxic breathing are seen.3,4 In general, the functional prognosis of the lateral medullary syndrome (LMS) is good, although a poor outcome was reported in some cases.5,6 We report herein a case of unilateral LMS that rapidly progressed to fatal respiratory failure with autopsy findings.
Case Report A 70-year-old man was referred to our hospital with nausea and vomiting, and unsteadiness while walking. He had a history of duodenal ulcer 30 years ago, but there was no history of hypertension, diabetes, hyperlipidemia,
Journal of Stroke and Cerebrovascular Diseases, Vol. 13, No. 1 (January-February), 2004: pp 41-44
41
S. TERAO ET AL.
42
or smoking. On the afternoon of the day before his hospitalization, he experienced a sudden onset of hidrosis on the head, a floating sensation, and difficulty in speaking, all of which resolved in 30 minutes. Soon thereafter, he started to deviate to the left side when he walked. Subsequently, he had two episodes of vomiting, but was able to take meals. He also had dull pain in the left occipital region. At the time of hospitalization he was lucid, with no evident intellectual impairment. His blood pressure was 200/130 mm Hg, pulse 80 beats per minute with no arrhythmia, and respiratory rate 17 breaths per minute. His height was 154 cm, he weighed 60 kg, and had a body temperature of 35.9°C. No bruit was heard in the neck. Neurologically, there were hoarseness, dysarthria, horizontal and rotatory nystagmus to the right gaze, the left central facial paralysis, the paralysis of the left soft palate, continuing hiccups, and dysphagia. No pupillary abnormalities, including Homer syndrome, were detected. There was no motor paralysis in the tongue or limbs. Decreased superficial sensation on the right face and upper limb was present. There was no abnormality in the deep sensations. The deep tendon reflexes were generally decreased. Babinski’s sign was not present. Cerebellar ataxia in the left upper and lower limbs was present. The blood gas analysis results were pH 7.42 in room air, PaO2 61.3 mm Hg, PaCO2 47.2 mm Hg, HCO3 29.7 mEq/1, and SaO2 92.5%, suggesting mildly impaired lung ventilation. Mild dehydration was suggested by the peripheral blood and biochemical tests. There were no abnormalities in the chest radiography, while electrocardiography showed mild hypertensive changes. There were no evident brain lesions on plain computed tomography. At this time, an ischemic lesion was suggested in the left dorsolateral portion of the medulla oblongata. Oxygen was administered at a dose of 1 1/min, and the patient was managed with hydration. The nausea, hiccups, and headache disappeared. At night 6 hours after admission (9:00 p.m.), his respiratory rate was regular at 30 to 35 breaths per minute when he was lucid, but during sleep, frequent apnea episodes of 5 to 10 seconds were noticed. There was no paralysis of the tongue, his blood pressure was 198/118 mm Hg, and his pulse was 100 to 110 beats per minute. Eleven hours after admission (2:00 a.m.), he was alert and responded well to the verbal orders. Saliva and sputum accumulated in his mouth, so frequent aspiration was performed. Sudden ataxic respiration appeared with the patient in a somnolent state one hour later (3:00 a.m.), and he died in the next hour. Continuous electrocardiography monitoring was conducted during hospitalization and there was no arrhythmia, ischemic changes, or any feature of heart failure. An endotracheal tube with mechanical ventilation was not placed. The scheduled head magnetic resonance imaging and cerebral angiography were not carried out.
Figure 1. Gross pathological findings of the cerebral arteries. The main arteries are showed: vertebral artery (VA), basilar artery (BA), posterior inferior cerebellar artery (PICA), anterior inferior cerebellar artery (AICA), superior cerebellar artery (SCA), middle cerebral artery (MCA), anterior cerebral artery (ACA).
Autopsy of the brain was subsequently performed. On gross examination, an atherothrombotic occlusion of the left vertebral artery was confirmed. The left posterior inferior cerebellar artery was not identified. The right posterior inferior cerebellar artery branched from the right vertebral artery, and the left anterior inferior cerebellar artery branched from the basilar artery (Fig 1). Histologically, there were fresh ischemic infarction localized to the left dorsolateral medulla, including the medullary reticular formation, the solitary nucleus, the intramedullary fibers of the vagus nerve, the nucleus ambiguus, and the spinal tract of the trigeminal nerve. In these regions, there were mild edema and pallor of Klu¨ ver-Barrera stain (Fig 2), dark staining and atrophy of the neurons, cells exhibiting eosinophilic ischemic changes, perivascular neutrophil and macrophage invasion, vacuolar degeneration, and axonal swelling around the malacia lesions. In addition, there was hypertrophy of the intima in the vertebral artery, basilar aretry, internal carotid artery, and middle cerebral artery. Occlusion of these arteries were not present.
Discussion This patient began clinically with typical left LMS, but within 24 hours, he progressed rapidly to show central
RESPIRATORY FAILURE IN LATERAL MEDULLARY SYNDROME
43
Figure 2. Histopathological transverse section at the level of the upper medulla (A). Klu¨ ver-Barrera stain ⫻ 7. The dorsolateral portion shows pallor (arrow). The right schema shows the neural architecture in the medulla oblongata (B). The location of key structures are marked: corticospinal tract (1); medial lemniscus (2); medial longitudinal fasciculus (3); hypoglossal nerve (XII) (4); hypoglossal nucleus (5); inferior olivary nucleus (6); spinothalamic tract (7); nucleus ambiguus (8); solitary nucleus (9); descending sympathetic tract (10); vagus nerve (X) (11); descending trigeminal tract (12); ascending trigeminal thalamic tract (13); inferior cerebellar peduncle (14); vestibular nucleus (15); dorsal nucleus of vagus (16); medullary reticular formation (17).
apnea, followed by ataxic respiration and, finally, respiratory failure leading to death. Symptomatologically, left central facial paralysis was observed in our patient. We studied to clarify the course of the facial corticobulbar tract in a large group of patients with lower brain stem infarction. We previously reported that the facial corticobulbar tract fibers descend at the ventromedial lower pons, near the corticospinal tract, mainly to the level of the upper medulla, where the fibers then decussate and ascend in the dorsolateral medulla to synapse in the contralateral facial nucleus.18,19 Ipsilateral central facial paralysis in the patient may have resulted from involvement to these ascending fibers. Decreased superficial sensation of right face was compatible with involvement to the ascending trigeminal thalamic tract in the left lateral medulla. Furthermore, decreased sensation of right upper limb was caused by the partial involvement of the spinothalamic tract.20 In our patient, no pupil abnormlities, including Horner syndrome, were detected. It may be spared the involvement of the descending central sympathetic tract in the lateral part of medulla (Fig 2).2 The respiratory functions including the voluntary, limbic, automatic, and reflex respirations relate to a multitude of structures extending from the cerebral cortex to the pontomedullary nuclei.2-4 The voluntary respiration is the system by which voluntary breathing movements are made during vigilance. The voluntary control origi-
nates at the cortical level, and its efferents appear to travel in the corticospinal tract.3,7 Automatic respiration, on the other hand, mainly regulates breathing automatically in response to the changes in oxygen and carbon dioxide in the blood, and changes in the movement of the lungs and thoracic cavity. Two centers are known to contribute to automatic respiration: the dorsal respiratory center in the ventrolateral part of the medullary solitary nucleus,1,3,4 and the ventral respiratory center, including the nucleus ambiguus, the dorsal nucleus of the vagus nerve, and the medullary reticular formation extending from the lower brainstem to the upper cervical cord.1,3 In the present case, there were neither abnormalities in the lungs, trachea, or thorax, nor neuromuscular diseases with impairment of the respiratory muscles. There was no motor paralysis of the limbs, and he could perform voluntary respiration in the alert state, indicating that the voluntary system was maintained. When he was lucid, however, he was in a hyperventilatory state. However, when he fell asleep or when his consciousness became impaired because of the accumulation of carbon dioxide, he progressively developed apnea or ataxic respiration. Taken together, it is presumed that impairment of the automatic respiration (Ondine’s curse)3,4,9,10 mainly occurred in the course of LMS and rapidly progressed to fatal respiratory failure. Several pathological investigations of LMS presenting as central apnea have been reported.7,8,10,11 Bogous-
S. TERAO ET AL.
44
slavsky et al8 reported that the automatic respiration was impaired by damage to the pontomedullary reticular formation and nucleus ambiguus, and that with a lesion of the solitary nucleus as well the voluntary respiration may also be affected. In contrast, Takehara et al11 reported that even if solitary nucleus impairment was present in addition to reticular formation and nucleus ambiguus disorders in LMS, only automatic respiratory disorder occurred; and there was no damage to the voluntary respiration. Our patient seemed to be similar to this latter report. Poor outcome in lateral medullary infarction patients can be caused by cerebellar infarction, dysphagia, abnormality of autonomic function or respiration, or a vascular occlusive lesion that causes progressive ischemia.5 Strokes complicated by Ondine’s curse usually result from a distal vertebral artery occlusion. When respiratory monitoring is performed, central respiratory abnormalities such as sleep apnea can be detected in LMS.12-14 The development of Ondine’s curse is a major determinant for poor outcome in this kind of stroke.5,6 The majority of reported clinicopathological studies describe patients with unilateral lateral medullary infarction.7,8 A leftsided predominance may be proposed for central control of respiration function.3 After crossing at the medullary level, the efferent fibers from the respiratory centers descend on both sides of the spinal cord, and thus a unilateral medullary lesion may affect the efferent pathways on both sides, and functionally impair respiration.8 Moreover, it has recently been pointed out that ischemia of the solitary nucleus in LMS may induce cardiopulmonary arrest in the acute stage.15,16 If LMS is suspected, one should take into account not only peripheral respiratory impairment such as aspiration,17 but also the possibility of the central, fatal impairment of apnea or ataxic respiration. Careful management with cardiopulmonary monitoring is particularly important in the acute stage of LMS. Acknowledgment: We are grateful to M. Yoshida, MD (Institute for Medical Science of Aging, Aichi Medical University School of Medicine) for the pathological comments.
References 1. Berger AJ, Mitchell RA, Severinghaus JW. Regulation of respiration: Second of three parts. N Engl J Med 1977; 297:138-143. 2. Plum F. Breathing is controlled independently by voluntary, emotional, and metabolically related pathways. Arch Neurol 1992;49:441.
3. Vingerhoets F, Bogousslavsky J. Respiratory dysfunction, In: Bogousslavsky J, Caplan LR (eds): Stroke syndromes. 2nd ed. Cambridge, MA, Cambridge University Press, 2001, 353-362. 4. Bassetti C, Aldrich MS, Quint D. Sleep-disordered breathing in patients with acute supra- and infratentorial strokes. A prospective study of 39 patients. Stroke 1997; 28:1765-1772. 5. Caplan LR, Pessin MS, Scott RM, et al. Poor outcome after lateral medullary infarcts. Neurology 1986;36:15101513. 6. Norrving B, Cronqvist S. Lateral medulary infarction: Prognosis in an unselected series. Neurology 1991;41: 244-248. 7. Levine BE, Margolis G. Acute failure of autonomic respirations secondary to a unilateral brainstem infarct. Ann Neurol 1977;1:583-586. 8. Bogousslavsky J, Khurana R, Deruaz JP, et al. Respiratory failure and unilateral caudal brainstem infarction. Ann Neurol 1990;28:668-673. 9. Severinghaus JW, Mitchel RA. Ondine’s curse—Failure of respiratory center automaticity while awake. Clin Res 1962;10:122. 10. Devereaux MW, Keane JR, Davis RL. Autonomic respiratory failure associated with infarction of the medulla. Report of two cases with pathologic study of one. Arch Neurol 1973;29:46-52. 11. Takehara M, Ishikawa K, Hiroi T, et al. Central type of sleep apnea syndrome caused by unilateral lateral medullary infarction. Rinsho Shinkeigaku 1992;32:511-515. 12. Askenacy JJM, Goldhammer I. Sleep apnea as a feature of bulbar stroke. Stroke 1988;19:637-639. 13. Good DC, Henkle JQ, Gelber D, et al. Sleep-disordered breathing and poor functional outcome after stroke. Stroke 1996;27:252-259. 14. Morrell MJ, Heywood P, Moosavi SH, et al. Unilateral focal lesions in the rostrolateral medulla influence chemosensitivity and breathing measured during wakefulness, sleep, and exercise. J Neurol Neurosurg Psychiatry 1999;67:637-645. 15. Caro RD, Parenti A, Montisci M, et al. Solitary tract nuclei in acute heart failure. Stroke 2000;31:1187-1193. 16. Jaster JH. Unexpected sudden death after lateral medullary infarction. J Neurol Neurosurg Psychiatry 2001;70: 137. 17. Kim H, Chung CS, Lee KH, et al. Aspiration subsequent to a pure medullary infarction. Lesion sites, clinical variables, and outcome. Arch Neurol 2000;57:478-483. 18. Terao S, Takatsu S, Izumi M, et al. Central facial weakness due to medial medullary infarction: The course of facial corticobulbar fibres. J Neurol Neurosurg Psychiatry 1997;63:391-393. 19. Terao S, Miura N, Takahashi A, et al. Course and distribution of facial corticobulbar tract fibres in the lower brain stem. J Neurol Neurosurg Psychiatry 2000;69:262265. 20. Kim JS. Pure lateral medullary infarction; clinical-radiological correlation of 130 acute, consecutive patients. Brain 2003;126:1864-1872.