Pathophysiological and Clinical Aspects of Breathing After Stroke 701

Home , Ataxic respiration, Hyperventilation, Respiratory arrest

700 Postgrad Med J 2001;77:700–702

Pathophysiological and clinical aspects of Postgrad Med J: first published as 10.1136/pmj.77.913.700 on 1 November 2001. Downloaded from breathing after stroke

R S Howard, A G Rudd, C D Wolfe, A J Williams

Stroke may disrupt breathing either by (A) (for review see Howard and Hirsch7). As a con- causing a disturbance of central rhythm sequence of lesions in this area automatic generation, (B) interrupting the descending respiratory control is disrupted; the patient is respiratory pathways leading to a reduced voluntarily able to maintain his respiratory pat- respiratory drive, or (C) causing bulbar weak- tern and breathes normally while awake and ness leading to aspiration. alert but during sleep there is a sudden or progressive decline in tidal volume and respiratory Pathophysiology of respiratory control in rate culminating in central apnoea. stroke Abnormal patterns of rate and rhythm are Neural control of respiration in man depends also often a reflection of impaired automatic on a central drive to the respiratory muscles ventilatory control.8 Primary central neurogenic which is modulated by chemical and mechani- hyperventilation is a rare condition character- cal inputs.1 While many of the factors control- ised by rapid, regular hyperventilation which ling established respiratory rhythm in mam- persists in the face of alkalosis, raised oxygen mals are understood, the neural mechanisms of tension, low carbon dioxide tension, and in the rhythm generation remain obscure.2–4 It has absence of any pulmonary or airway disor- proved diYcult, in man, to attribute precise der.910 However, hyperventilation in the post- respiratory function to localised anatomical stroke patient is common but is due to intrinsic substrates because lesions are rarely localised pulmonary involvement.11–13 In apneustic and coexisting pulmonary, cardiovascular, or breathing there are sustained inspiratory autonomic influences may complicate the cramps with a prolonged pause at full inspira- clinical picture. Furthermore accurate diagno- tion or alternating brief end inspiratory and sis of respiratory insuYciency has led to earlier expiratory pauses. The pattern has been therapeutic intervention with controlled venti- associated with bilateral tegmental infarcts in lation. Also there is probably considerable the pons. Ataxic respiration is characterised by a redundancy and plasticity of the neural sub- completely irregular respiratory cycle of vari- able frequency and tidal volume alternating Department of strate of respiratory control, thus congenital, Neurology, Guy’s and longstanding, or slowly progressive and de- with periods of apnoea. It is particularly St Thomas’ Hospital structive mass lesions can have little or no associated with medullary impairment either Trust, London and functional consequence while acute discrete due to brainstem stroke or compression due to Batten Harris lesions in a similar distribution may lead to rapidly expanding lesions and may be an Neuromedical profound respiratory impairment. Finally important sign of impending respiratory arrest. http://pmj.bmj.com/ Intensive Care Unit, Hiccups consist of brief bursts of intense National Hospital for much of the literature is flawed because the Neurology and extensive experimental animal work has been inspiratory activity involving the diaphragm Neurosurgery, Queen applied to man without any evidence for and inspiratory intercostal muscles with recip- Square, London rocal inhibition of the expiratory intercos- anatomicophysiological correlates. However in 14 15 RSHoward individual case studies abnormalities of respi- tals. Glottic closure occurs almost immedi- ately after the onset of diaphragmatic Department of Elderly ration may be associated with small, discrete lesions of the central nervous system, defined contraction thus minimising the ventilatory

Care, Guy’s and St on October 2, 2021 by guest. Protected copyright. Thomas’ Hospital by imaging or postmortem, particularly due to eVect. Intractable hiccups may be the result of Trust, London stroke. Such reports have complemented ex- structural or functional disturbances of the A G Rudd perimental animal work and have greatly medulla or its aVerent or eVerent connections increased our understanding of the mecha- with the respiratory muscles This may be asso- Department of Public ciated with structural lesions of the medulla Health Medicine, nisms that control breathing in man. Central respiratory drive is mediated by including infarction in the territory of the pos- Guy’s, King’s and St terior inferior cerebellar artery. The develop- Thomas’ School of three pathways, which are largely anatomically Medicine, London and functionally independent above the seg- ment of hiccups in this context may anticipate C D Wolfe mental level,1 although it is increasingly clear the development of irregularities of the respira- that these systems must interact with one tory rhythm culminating in respiratory arrest. Lane Fox Unit, St another to some extent.56 Thomas’ Hospital BEHAVIOURAL (VOLUNTARY) RESPIRATION Trust, London A J Williams Behavioural (voluntary) respiration operates METABOLIC (AUTOMATIC) RESPIRATION during wakefulness and allows voluntary Correspondence to: Metabolic (automatic) respiration is the ho- modulation of respiration in response, for Dr Robin Howard, moeostatic pathway by which ventilation may example, to speaking, singing, breath holding, Department of Neurology, St Thomas’ Hospital, Guy’s and be mediated to maintain acid-base status and and straining. Volitional control is active during St Thomas’ Hospital Trust, oxygenation to the metabolic requirements. consciousness but quiescent during sleep, Lambeth Palace Road, Automatic control is mediated by localised although it may be involved in the chaotic res- London SE1 7EH, UK areas in the dorsolateral tegmentum of the piratory patterns seen during rapid eye move- Submitted 2 April 2001 pons and medulla in the region of the nucleus ment sleep. Voluntary control may be impaired Accepted 15 May 2001 tractus solitarius and nucleus retroambigualis by bilateral lesions aVecting the descending

www.postgradmedj.com Pathophysiological and clinical aspects of breathing after stroke 701

corticospinal or corticobulbar tracts,5 and is Patterns of respiratory impairment due Postgrad Med J: first published as 10.1136/pmj.77.913.700 on 1 November 2001. Downloaded from particularly seen in association with destructive to stroke vascular lesions of the basal pons or of the CORTEX medullary pyramids and adjacent ventromedial Hemispheric ischaemic strokes influence respi- portion which may result in the “locked in” ratory function to a modest degree. Reductions syndrome.16 Selective interruption of the vol- of both chest wall and diaphragm excursion untary pathways in man leads to a strikingly contralateral to the stroke have been re- regular and unvarying respiratory pattern dur- ported.24 25 The latter association correlates ing wakefulness as well as sleep, with loss of the well with the localisation of the diaphragm cor- ability to take a deep breath, hold the breath, tical representation found by transcranial mag- cough voluntarily, or initiate any kind of netic stimulation and positron emission tomog- volitional respiratory movement. The tidal vol- raphy scanning.26–31 At present there is no clear ume remains responsive to carbon dioxide and evidence of cerebral dominance for diaphragm a reflex cough is preserved.17 DiVuse cortical function. vascular disease may lead to selective abnor- Patients with bilateral hemispheric cerebro- malities of voluntary breathing such that there vascular disease show an increased respiratory is an inability to take a deep breath or to hold responsiveness to carbon dioxide and are liable the breath to command. These respiratory to develop Cheyne-Stokes respiration suggest- apraxias may be associated with inability to ini- ing disinhibition of lower respiratory centres. tiate voluntary swallowing or with other behav- Such a response may persist months to years ioural apraxias.118 Cheyne-Stokes respiration is after the stroke. DiVuse cortical vascular characterised by a smooth waxing and waning disease may also lead to a selective inability of of breath volume and frequency separated by voluntary breathing (respiratory apraxia).18 19 20 periods of apnoea ; the hyperpnoeic phase is Intermittent upper airway obstruction and longer than the apnoea and the entire cycle apnoea due to periodic fluctuations in the typically lasts one minute or more. The position of the vocal cords is associated with respiratory oscillations are associated with cortical supranuclear palsy due to bilateral phasic changes in cerebral blood flow, cerebro- lesions of the operculum.32 spinal fluid pressure, arterial and alveolar oxygen and carbon dioxide, level of alertness and pupillary size; periodic heart block and ven- BRAINSTEM tricular arrhythmias are also common. It has The eVects of brainstem dysfunction on respi- been suggested that Cheyne-Stokes respiration ration depend on the pathology, localisation, may occur in up to 50% of patients after and speed of onset of the lesion. In patients unilateral supratentorial stroke21 22 and, despite with bulbar lesions, particularly vascular, the the observations of Plum and Posner, it may combination of impaired swallow, abnormali- also be common after infratentorial stroke. ties of the respiratory rhythm, reduced vital Studies in these patients show the frequency capacity, and reduced or absent triggering of variations of respiratory amplitude modulation cough reflex all increase the risk of aspiration is low suggesting that Cheyne-Stokes respira- pneumonia.33 Nocturnal upper airway occlu-

tion represents a relatively uniform response to sion may also contribute to respiratory impair- http://pmj.bmj.com/ central nervous system injury regardless of inf- ment. Unilateral or bilateral lateral tegmental arct size or location. During Cheyne-Stokes infarcts in the pons (at or below the level of the respiration there are concomitant periodic trigeminal nucleus) may lead to apneustic drops in arterial oxygen saturation compromis- breathing and impairment of carbon dioxide ing the vulnerable hypoperfused peri-infarct responsiveness,34 while similar lesions in the tissue of the ischaemic penumbra. medulla (for example, lateral medullary syndrome) may result in acute failure of the auto-

35 36 on October 2, 2021 by guest. Protected copyright. LIMBIC (EMOTIONAL) RESPIRATION matic respiration. Infarction of the basal Limbic (emotional) respiration accounts for pons (locked in syndrome) or of the pyramids the preservation of respiratory modulation to and the adjacent ventromedial portion of the emotional stimuli including laughing, cough- medulla may lead to complete loss of the ing, and anxiety despite loss of voluntary con- voluntary system with a highly regular breath- trol. This implies that descending limbic inﬂu- ing pattern but a complete inability to initiate ences on automatic respiration are anato- any spontaneous respiratory movements.37 mically and functionally independent of the Acute vascular lesions in the lower brainstem voluntary respiratory system. Munschauer et al compromise respiratory control, particularly described a patient with locked in syndrome during sleep, leading to irregularities of rate due to infarction of the basal pons, this led to and rhythm of breathing which lead to loss of voluntary control but carbon dioxide Cheyne-Stokes respiration, hypopnoea, and responses remained normal.23 This patient obstructive apnoea.38 39 It is likely that size and showed preserved respiratory modulation to bilaterality of the lesions determine the type emotional stimuli including coughing and and severity of abnormalities of the respiratory anxiety and in another patient laughing.17 Such pattern. In a series of 15 patients with vascular an independent descending pathway, mediat- lesions of the lower brainstem, patients with ing limbic control of respiration lies either in unilateral lesions in the rostrolateral medulla the pontine tegmentum or lateral basis pontis. showed a reduced ventilatory sensitivity to Such limbic pathways are also suggested by the inhaled carbon dioxide. In these patients there eVect of limbic cortex stimulation and epileptic was a minimal eVect on breathing while awake, seizures. at rest or during exertion, however there was a

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high incidence of fragmented sleep and ob- 8 Plum F, Posner JB. Posthyperventilation apnoea. In: Plum F, Postgrad Med J: first published as 10.1136/pmj.77.913.700 on 1 November 2001. Downloaded from Posner JB, eds. Diagnosis of stupor and coma. 3rd Ed. structive sleep apnoea associated with hypox- Philadelphia: FA Davis, 1983: 33. aemia. The authors concluded that patients 9 Rodriguez M, Beale PL, Marsh HM, et al. Central neurogenic hyperventilation in an awake patient with brain- with unilateral rostrolateral medullary lesions stem astrocytoma. Ann Neurol 1982;11:625–8. require monitoring during sleep to diagnose 10 Pauzner R, Mouallem M, Sadeh M, et al. High incidence of 38 primary cerebral lymphoma in tumour-induced central sleep apnoea. neurogenic hyperventilation. Arch Neurol 1989;46:510–12. Isolated central sleep apnoea due to brain- 11 Mazzara JT, Ayres SM, Grace WJ. Extreme hypocapnia in the critically ill patient. Am J Med 1974;56:450–6. stem vascular disease is usually associated with 12 North JB, Jennett S. Abnormal breathing patterns associ- bilateral lesions caudal to the V cranial nerve in ated with acute brain damage. Arch Neurol 1974;31:338–44. the pons down to the ventral lateral, tegmental 13 Leigh RJ, Shaw DA. Rapid, regular respiration in uncon- scious patients. Arch Neurol 1976;33:356–61. pons, medulla, and cervical spinal cord. Occa- 14 Newsom Davis J. An experimental study of hiccup. Brain sional reports have described central apnoea 1970;93:851–72. 15 Howard RS. The causes and treatment of intractable with unilateral lesions involving nucleus am- hiccups. BMJ 1992;305:1237–8. biguus but sparing nucleus tractus solitarius; 16 Patterson JR, Grabois M. Locked in syndrome: a review of 139 cases. Stroke 1986;17:758–65. however the relevance of these is diYcult to 17 Heywood P, Murphy K, Corfield DR, et al. Control of assess with limited respiratory, imaging, and breathing in man; insights from the “locked-in” syndrome. 39 Respir Physiol 1996;106:13–20 neuropathological information. 18 Hebertson WM, Talbert OR, Cohen ME. Respiratory apraxia and anosogosia. Trans Am Neurol Assoc 1959;84: 176–9. CERVICAL CORD 19 Tobin MJ, Snyder JV. Cheyne-Stokes respiration revisited. Infarction of the spinal cord at high cervical Controversies and implications. Crit Care Med 1984;12: levels may selectively aVect respiratory con- 882–7. 40 41 20 Naughton MT. Pathophysiology and treatment of Cheyne- trol. Lesions of the anterior pathways, Stokes respiration. Thorax 1998;53:514–18. particularly descending reticulospinal, lead to 21 Lee MC, Klassen AC, Resch JA. Respiratory pattern disturbances in ischaemic cerebrovascular disease. Stroke 1974;5: loss of automatic control and sudden nocturnal 612–16. death from apnoea while involvement of the 22 Nachtmann A, Siebler M, Rose G. Cheyne-Stokes respiration in ischaemic stroke. Neurology 1995;45:820–1 dorsolateral corticospinal tracts may lead to 23 Munschauer FE, Mador MJ, Ahuja A, et al. Selective automatic respiration of the type described paralysis of voluntary but not limbically influenced automatic respiration. Arch Neurol 1991;48:1190–2. earlier. Infarction of the spinal cord at high 24 Houston JG, Morris AD, Grosset DG, et al. Ultrasonic cervical levels is usually due to occlusion of the evaluation of movement of the diaphragm after acute cerebral infarction. J Neurol Neurosurg Psychiatry 1995;58: anterior spinal artery and may be due to fibro- 738–41. cartilaginous embolism.42 Patients may present 25 Cohen E, Mier A, Heywood P, et al. Diaphragmatic movement in hemiplegic patients measured by ultrasonog- with neck or shoulder pain but then develop a raphy. Thorax 1994;49:890–5. rapidly evolving tetraplegia and respiratory 26 Gandevia SC, Rothwell JC. Activation of the human diaphragm from the motor cortex. J Physiol 1987;384:109– insuYciency culminating in respiratory arrest. 18. Complete anterior spinal artery occlusion 27 Macefield G, Gandevia SC. The cortical drive to human respiratory muscles in the awake state assessed by premotor causing infarction that extends up to C1 has a cerebral potentials. J Physiol 1991;439:545–58. poor outlook, while incomplete occlusion at 28 Colebach JG, Adams L, Murphy K, et al. Regional cerebral blood flow during volitional breathing in man. J Physiol C3/4 may show significant recovery of respira- 1991;443:91–103. tory and limb function.43 29 Maskill D, Murphy K, Mier A, et al. Motor cortical representation of the diaphragm in man. J Physiol 1991;443: Respiration is commonly aVected after 105–21.

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