Anterior Spinal Artery Syndrome Complicated by the Ondine Curse

Home , Cordotomy, Dissociated sensory loss

OBSERVATION Anterior Spinal Artery Syndrome Complicated by the Ondine Curse

Mauro Manconi, MD; Susanna Mondini, MD; Andrea Fabiani, MD; Paolo Rossi, MD; Paolo Ambrosetto, MD; Fabio Cirignotta, MD

Background: Anterior spinal artery (ASA) syndrome re- showed a severe sleep disruption caused by continuous sults in motor palsy and dissociated sensory loss below central apneas that appeared immediately after falling the level of the lesion, accompanied by bladder dysfunc- asleep. Treatment by intermittent positive pressure ven- tion. When the cervical spine is involved, breathing dis- tilation normalized the respiratory pattern and sleep ar- orders may be observed. chitecture.

Objective: To describe the polysomnographic find- Conclusions: The sleep breathing pattern was compat- ings in a patient with cervical ASA syndrome compli- ible with central alveolar hypoventilation due to auto- cated by a sleep breathing disorder. matic breathing control failure caused by a lesion of the reticulospinal pathway, which normally activates venti- Setting: Unit of neurology at a sleep center. latory muscles during sleep. This autonomic sleep breathing impairment resembles that found as a complication Patient: A 30-year-old man had an ischemic lesion that in patients who undergo spinothalamic tract cervical cor- affected the anterior cervical spinal cord (C2-C6) bilater- dotomy for intractable pain. This surgical complication ally because of an ASA thrombosis. He developed ASA syn- is known as the Ondine curse. drome associated with respiratory impairment during sleep.

Results: The polysomnographic study during sleep Arch Neurol. 2003;60:1787-1790

NTERIOR SPINAL artery(ASA) REPORT OF A CASE occlusion is an uncommon event that may cause ischemia of the ventral two thirds A 30-year-old man was admitted to the Neu- ofthespinalcord,withsigns rological Unit–Sleep Centre of St Orsola- andA symptoms exhibited below the level of Malpighi Hospital (Bologna, Italy) be- the lesion. These include central motor im- cause of ventilatory failure during sleep. pairment, dissociated sensory failure, and Three months before, cerebrospinal mag- bladder dysfunction. When the ischemia in- netic resonance angiography (MRA) re- volves the ventral horns, a suspended lower vealed an ischemic lesion affecting the an- motor neuron deficit may occur. The most terior spinal cord bilaterally (C2-C6) as a frequent causes of ASA syndrome are aor- consequence of ASA thrombosis. He exhib- tic dissection or traumatic rupture, compli- ited sudden tetraplegia and respiratory ar- cations of aortic surgery, thrombosis or rest, requiring mechanical ventilation by tra- embolism, hematomyelia, vasculitis, verte- cheostomy. In the days following, he brocervical arthrosis, and coagulopathy; recovered motor activity in his legs and dis- however,somecasesremaincryptogenetic.1,2 tal arms. He experienced complete reha- Themidthoracicregion(T4toT8)isthemost bilitation of breathing while awake but not From the Units of Neurology vulnerable one to ischemic damage, owing while asleep and thus required intermit- (Drs Manconi, Mondini, and to its relative hypovascularity. Injury to the tent positive pressure ventilation (IPPV) Cirignotta) and Respiratory upper cervical spinal cord may result in during sleep. The results of blood tests, in- Physiopathology (Dr Fabiani), breathing dysfunctions due to impairment cluding inflammatory markers, coagula- St Orsola-Malpighi Hospital, of the descending pathways that subserve tory parameters, and an autoantibody pro- and the Department of thevoluntaryandautonomicventilatorycon- file, were normal. Dynamic cineradioscopy Neurological Sciences, trol. Likewise, impairment of the C2 to C4 showed a bilateral diaphragmatic palsy. His University of Bologna, spinal segments, from which lower ventilatory effort while awake was sup- (Dr Ambrosetto), Bologna, and motor neurons innervate the diaphragm, ported by intercostals, other accessory res- the Department of 3 Anaesthesiology and may cause breathing dysfunctions. Here, piratory muscles, and residual diaphrag- Reanimation, St Benedetto we report the polysomnographic findings matic contraction. The spirometry showed Hospital, St Benedetto del in a case of ASA syndrome with a sleep a mild restrictive syndrome. At night, IPPV Tronto (Dr Rossi), Italy. breathing disorder. via tracheostomy was required (tidal vol-

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 ume, 540 mL; respiratory rate, 11/min) because he re- SLEEP STUDIES ported being “unable to fall asleep without it.” Several trials to wean him off the mechanical ventilation during sleep Five nighttime polysomnographic studies were per- failed. With the diagnosis of idiopathic ASA syndrome, he formed in a single-bed room; the following tests were was referred to our sleep center for a polysomnographic done: electroencephalography (C3/A2, CZ/A1, O2/A1); study of breathing patterns. At the time of our examina- electro-oculography (ROC/A1, LOC/A1); electromyog- tion, no cognitive or cranial nerve deficits were found. There raphy of submental, right intercostal, rectus abdomina- was hypotrophy and flaccid palsy of the bilateral girdle lis, and left anterior tibialis muscles; airflow (oronasal muscles of upper limbs with preserved strength of the dis- thermistor during breathing by closed tracheostomy, and tal arms, mild spastic paraparesis predominant on the left thermistor positioned in front of the stoma during breath- side, dissociated sensory loss below C2 to C3, a bilateral ing by opened tracheostomy); chest and abdominal move- Babinski sign, and sphincteric and erectile dysfunction. ments (inductive plethysmography); electrocardio- While awake, his breathing was spontaneous with the closed graphy; finger probe pulse oximetry (SaO2); and tracheostomy, respiratory rate was 20/min to 22/min, and transcutaneous capnography (TCO2). Each recording was the results of a blood gas analysis were normal (PaCO2, 38.1 performed in different respiratory conditions: during spon- mm Hg; PaO2, 63.8 mm Hg; pH, 7.42). Brainstem evoked taneous ventilation by closed and by open tracheos- potentials were normal. tomy, during IPPV by tracheostomy nasal mask (respiratory rate, 11/min; tidal volume, 540 mL), and during sleep induction by triazolam (0.25 mg at 11 PM). Fur- thermore, the flow distribution of IPPV by tracheostomy was manually stopped during slow-wave sleep and during rapid eye movement (REM) sleep to evaluate the functioning of automatic breathing control in consoli- dated sleep. Sleep was manually scored in 20-second ep- ochs according to the standard criteria of Rechtschaffen and Kales.4

POLYSOMNOGRAPHIC RESULTS

During spontaneous breathing, the sleep respiratory pattern was characterized by continuous central apneas that appeared immediately after falling asleep and persisted throughout the entire sleep period. These episodes lasted 10 to 30 seconds and were associated with mild oxygen desaturation (3%-6%). The apneas ended with arousal or awakening, leading to severe sleep disruption (Figure 1). The total bed time for the first night was 6 hours 41 minutes, and the total sleep time was 3 hours 55 minutes, completely constituted by stage 1 and 2 non- Figure 1. Continuous central apneas in stage 2 of non–rapid eye movement sleep during spontaneous respiration. During the apneas, no thoracic or REM. Slow-wave and REM sleep were absent. During abdominal movements or intercostal muscle activity was observed. wakefulness, the respiratory rate was 20/min, with regu-

C3 - A2

O2 - A1 Cz - A1 R EOG L EOG Mylo

ECG Interc EMG

Oral Nasal Resp Thor Resp

Abdom Resp 50 µV 1 s

Figure 2. Normal sleep architecture with slow-wave sleep and rapid eye movement sleep during mechanical ventilation. Abdom Resp indicates abdominal respirations; ECG, electrocardiogram; EMG, electromyogram; EOG, electro-oculogram; Interc, intercostal; Mylo, myloioideus muscle and Thor Resp, thoracic respirations.

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C3 - A2

O2 - A1

Cz - A1

R EOG

L EOG

ECG

Interc EMG

Oral Nasal Resp

Thor. Resp

50 µV 1 sec REM

C3 - A2

O2 - A1

Cz - A1

R EOG

L EOG

ECG

Interc EMG

Oral Nasal Resp

Thor Resp

50 µV 1 s

Figure 3. Sagittal (A) and axial (B) T2-weighted magnetic resonance images show linear hyperintensity in the anterior spinal cord, extending from C2 to C6, suggesting infarction in the territory of the anterior spinal artery. Note that the cervicobulbar junction is normal. ECG indicates electrocardiogram; EMG, electromyogram; EOG. eletro-oculogram; Interc, intercostal; NREM, non-rapid eye movement; Resp, respirations; and Thor, thoracic. lar electromyographic intercostal activity. The cheostomy, confirming a central sleep apnea pattern administration of 0.25 mg of triazolam did not change associated with severe sleep disruption. The following the breathing pattern except for a mild lengthening of year, IPPV by nasal mask was successful, yielding the the apneas. The IPPV supply led to a regular respiratory same good respiratory and sleep results obtained during pattern during a complete sleep cycle, with a constant ventilation by stoma. The tracheostomy has since been respiratory rate of 11/min, no intercostal activity, and no removed, and the patient has been breathing with an SaO2 fluctuations (Figure 2). With IPPV by tracheos- IPPV nasal mask every night. After 4 years, repeated tomy, the ventilation was manually stopped during slow- cerebrospinal MRA revealed the anterior spinal cord wave sleep (3 times) and REM sleep (3 times). On each lesion extending from C2 to C6, with no brainstem occasion, central apneas reappeared immediately after dis- involvement (Figure 3). continuation of assisted ventilation, with the same respiratory pattern. COMMENT FOLLOW-UP The sleep breathing disorder in this patient was characterized by continuous central apneas associated with severe At the 1-year follow-up, polysomnography was per- sleep disruption. The apneas appeared immediately after formed during spontaneous breathing with a closed tra- falling asleep and were followed by arousal or complete

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 mitted easier identification of reticulospinal tract localiza- tion in the shelter of the spinothalamic pathway (Figure 4).11-12 Similarly, the ischemic lesion in our pa- Corticospinal Tract tient involved the spinothalamic tracts, causing dissociated sensory loss and, as a result of the tight nearness, the s l t c interruption of the reticulospinal tract subserving auto- Bladder nomic ventilation. We believe ours is the first report of poly- Fibers s somnographic demonstration of Ondine curse in ASA syn- l drome and other diseases and locations of spinal cord t Spinothalamic lesions, except for surgical cordotomy. A detailed study, and Reticulospinal c Spinoreticular using standard laboratory polysomnography, should al- Tract Tracts ways be performed if breathing dysfunction associated with (Respiratory-Intercostal Diaphragmatic) Common Area of a cervical lesion occurs in the absence of bulbar respira- Cordotomy Lesion tory center injury. Results of nocturnal oximetry monitor- ing or polygraphic portable recording do not provide an Figure 4. High cervical spinal section. Sites of the surgical lesion for intractable pain (right side) and of the ischemic area in anterior spinal artery syndrome (left accurate diagnosis of this condition. Based on our find- side) and their topographic relationship with the reticulospinal tract. c indicates ings, we recommend nasal mask IPPV to resolve breath- cranial; l, lumbar; s, sacral; and t, thoracic. ing dysfunctions and normalize the sleep architecture in these patients. awakening. During IPPV, the sleep architecture and respiratory pattern were regular. While awake, the patient breathed spontaneously by residual diaphragmatic activ- Accepted for publication July 18, 2003. ity and intercostal and accessory respiratory muscles, in line Author contributions: Study concept and design (Drs with the integrity of the direct pyramidal tracts.5 The fact Manconi, Mondini, and Cirignotta); acquisition of data (Drs that triazolam taken before sleep did not change the res- Fabiani, Rossi, Mondini, and Cirignotta); analysis and in- piratory pattern, together with the immediate reappear- terpretation of data (Drs Manconi, Ambrosetto, Mondini, ance of central apneas in slow-wave sleep and REM after and Cirignotta); drafting of the manuscript (Drs Manconi, stopping IPPV, the possibility that psychological depen- Fabiani, Rossi, Mondini, and Cirignotta); critical revision dency on mechanical ventilation could influence the breath- of the manuscript for important intellectual content (Drs Am- ing pattern ruled out. The persistence of the breathing dis- brosetto and Cirignotta); obtained funding (Dr Cirignotta). order during spontaneous ventilation with opened Corresponding author and reprints: Fabio Cirignotta, tracheostomy excluded any obstructive mechanism in the MD, Unit of Neurology, St Orsola-Malpighi Hospital, Via pathogenesis of the apneas. This pattern cannot be ex- Albertoni 14, 40138 Bologna, Italy (e-mail: cirignotta plained on the basis of the diaphragmatic palsy. The dia- @orsola-malpighi.med.unibo.it). phragmatic hypomobility falls within the restrictive forms of respiratory failure, which could cause REM hypoventi- REFERENCES lation via the inhibition of accessory muscles, which is typi- cal of REM atonia.5-8 Further, no electromyographic inter- 1. Salvador de la Barrera S, Barca-Buyo A, Montoto-Marques A, Ferreiro-Velasco costal activity was found during each episode of apnea, as ME, Cidoncha-Dans M, Rodriguez-Sotillo A. 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Correction

Errors in Figure Legends. In the Observation titled “Anterior Spinal Artery Syndrome Complicated by the Ondine Curse,” published in the December is- sue of the ARCHIVES (2003;60:1787-1790), the legends to Figures 1, 2, and 3 were incorrect. The legends are reprinted correctly as follows. Figure 1. Axial T2-weighted magnetic resonance image shows linear hyperintensity in the anterior spinal cord, extending from C2 to C6, suggesting infarction in the territory of the anterior spinal artery. Note that the cervicobulbar junction is normal. Figure 2. Continuous central apneas in stage 2 of non–rapid eye movement sleep during spontaneous respiration. During the apneas, no thoracic or abdominal movements or intercostal muscle activity were observed. Abdom Resp indicates abdominal respirations; ECG, electrocardiogram; EMG, electromyogram; EOG, electro-oculogram; Interc, intercostal; Mylo, myloioideus muscle; Oral Nasal Resp, oral nasal respirations; and Thor Resp, thoracic respirations. Figure 3. Normal sleep architecture with slow-wave sleep and rapid eye movement sleep during mechanical ventilation. ECG indicates electrocardiogram; EMG, electromyogram; EOG, electro-oculogram; Interc, intercostal; Oral Na- sal Resp, oral nasal respirations; REM, rapid eye movement; NREM, non– rapid eye movement; Thor Resp, thoracic respirations.

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