Thorax Online First, published on January 13, 2017 as 10.1136/thoraxjnl-2016-208786 Chest clinic CASE BASED DISCUSSION Thorax: first published as 10.1136/thoraxjnl-2016-208786 on 13 January 2017. Downloaded from Acquired central hypoventilation following Listeria monocytogenes rhombencephalitis Sandrine H Launois,1,2 Natalia Siyanko,2 Marie Joyeux-Faure,1,2 Renaud Tamisier,1,2 Jean-Louis Pepin1,2 1HP2 Unit, Inserm U1042, INTRODUCTION events/hour, oxygen desaturation index of 64 Grenoble Alpes University, Acquired central hypoventilation syndrome (CHS) events/hour, time spent under 90% oxygen satur- Grenoble, France 2Department of Physiology and is a rare cause of respiratory failure. We report a ation of 287 min or 82% of total sleep time) with Sleep, Grenoble University case of acquired CHS, diagnosed several years after persistent daytime alveolar hypoventilation Hospital, Grenoble, France Listeria monocytogenes (LM) rhombencephalitis. (PaCO2=7.64 kPa, PaO2=9.61 kPa). The AHI was 34 events/hour during non-rapid eye movement Correspondence to (REM) sleep and 41 events/hour during REM Dr Sandrine H Launois, CASE REPORT Département Physiologie In 1993, a 46-year-old woman presented to our sleep. Prolonged periods of shallow breathing with Algologie Somnologie, Unité Sleep Clinic with poor sleep, nocturnal choking sustained hypoxaemia were noted in non-REM as de Somnologie et Fonction episodes and daytime fatigue. She denied habitual well as REM sleep (transcutaneous CO2 measure- Respiratoire, Hôpital ment was not available). Ataxic breathing alternated Universitaire Saint Antoine, snoring and hypersomnolence. Her medical history 184 rue du Faubourg Saint was unremarkable except for severe LM rhomben- with central apnoeas and hypopneas lasting up to Antoine, Paris 75012, France; cephalitis in 1977. At that time, the patient had 59 s. Ventilatory CO2 response, assessed by the [email protected] been hospitalised in the intensive care unit follow- Read closed-circuit technique, was blunted (figure ing the acute onset of fever, influenza-like symp- 1), confirming profound central chemo sensitivity Received 17 April 2016 impairment. Standard pulmonary function testing Accepted 13 December 2016 toms, meningism, facial palsy and nystagmus. Blood and cerebral spinal fluid samples were posi- showed no abnormality. PHOX-2B mutation was tive for LM on direct microscopic exam as well cul- excluded by genetic testing. Brainstem MRI showed tures. Treatment was initiated but the patient two round hypodense defects in the area of respira- acutely deteriorated, exhibiting tetra paresis, bilat- tory centres (figure 2). Non-invasive bi-level noc- eral pontomedullary syndrome, impairment of vigi- turnal ventilation was initiated shortly after the lance, and experienced a cardiac arrest. She was sleep study. Although alveolar ventilation was successfully resuscitated and remained in the inten- rapidly corrected with non-invasive ventilation, sive care unit with gradual and slow recovery. After nocturnal and daytime symptoms were slower to Chest clinic improve. In 2012, a polysomnogram while on noc- a lengthy hospital stay, she was eventually dis- http://thorax.bmj.com/ charged from the hospital and resumed a normal turnal ventilation showed an AHI of 4.2 events/ life, with few neurological sequelae such as dyspha- hour. Initially adherence to non-invasive ventilation gia and mild facial palsy. To investigate the patient’s was poor but gradually increased to reach a mean sleep complaints, an in-laboratory full polysomno- nightly use of 7 hours in 2014. graphy was obtained and revealed central sleep apnoeas and hypopnoeas (Apnoea–Hypopnoea DISCUSSION index (AHI)=50 events/hour) with severe nocturnal In mammals, automatic respiratory drive originates hypoxaemia. Morning arterial blood gases revealed from and is modulated by neuronal networks on October 1, 2021 by guest. Protected copyright. alveolar hypoventilation with partial pressure of located in the pons and medulla oblongata.1 arterial CO2 or PaCO2 of 6.7 kPa and PaO2 of Central chemoreceptors, which respond to varia- 9.5 kPa. The patient refused further investigations tions in blood CO2 levels, are spread at the surface and therapy but agreed to return to clinic for a of the ventral medulla and allow minute ventilation follow-up in 1 year. In 1994, polysomnography adjustments to maintain PaCO2 and pH homoeo- and arterial blood gases showed persistent sleep stasis.2 In addition to specific respiratory centres, apnoea and daytime hypoventilation but the patient the neighbouring solitary tract nucleus is crucial for continued to decline treatment. The patient was the control of breathing, as it integrates informa- then lost to follow-up until 2011, when she pre- tion from peripheral and central receptors.2 sented for the third time to the Sleep Clinic com- Vigilance states have a strong effect on respiratory plaining of daytime fatigue, unrefreshing sleep, centre control.2 Thus, it is not surprising that cases choking episode during sleep and daily morning of CHS secondary to brainstem damage have been headaches, with a body mass index of 21.67 kg/m2 reported following infarction, compression, brain- and no comorbidity at the time of diagnosis. stem tethering, tumour or infection. Bilateral injury To cite: Launois SH, Clinical examination showed ataxic respiration of these areas results in rapid death. However, less Siyanko N, Joyeux-Faure M, while awake, mild left peripheral facial palsy, and extensive damage may be compatible with survival et al. Thorax Published Online First: [please include asymmetrical elevation of the soft palate. Once but causes respiratory centre dysfunction and Day Month Year] again, the patient underwent polysomnography and central hypoventilation. doi:10.1136/thoraxjnl-2016- morning arterial blood gases analysis, confirming LM is a gram-positive bacillus that can cause 208786 disrupted sleep, central sleep apnoea (AHI=35 opportunistic foodborne infections and is Launois SH, et al. Thorax 2017;0:1–3. doi:10.1136/thoraxjnl-2016-208786 1 Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd (& BTS) under licence. Chest clinic Thorax: first published as 10.1136/thoraxjnl-2016-208786 on 13 January 2017. Downloaded from Figure 1 Ventilatory response to CO2 performed in 2011. The patient’s response slope was 0.6 L/min/mm Hg (closed circles). The normal range for the laboratory is 1.5–3.5 L/min/mm Hg. Mean expected values are shown in open circles. associated with a high mortality rate.3 Because of its ability to inconclusive but MRI typically reveals multiple abscesses in the cross the blood-brain barrier, LM can infect the central nervous brain stem and the cerebellum. Autopsy may show non-specific system (CNS) and lead to encephalitis, meningitis, cerebellar inflammation but usually confirms the presence of unilateral or abscess or rhombencephalitis (or brainstem encephalitis).3 bilateral multiple abscesses located in the brainstem and cultures Although its exact prevalence remains unknown, LM rhomben- are positive for LM.3 In our patient, neither cerebral CT scan cephalitis is an uncommon infection in humans.3 Unlike other nor MRI scans had been performed at the time of the initial forms of listeriosis, predisposing factors are usually absent in infection but cerebral MRI scans obtained 34 years after the Chest clinic patients developing rhombencephalitis, as was the case for our acute episode revealed two hypodense brainstem lesions, which patient. After a non-specific prodromal phase, evidence of brain argue against a congenital cause which would not exhibit these http://thorax.bmj.com/ stem dysfunction appears, often leading to a fatal outcome, par- types of MRI abnormalities.4 Diagnosis and treatment may be ticularly when treatment is delayed.3 With proper early anti- delayed because symptoms are non-specific, blood and cerebro- biotic therapy and supportive care, the mortality rate decreases spinal fluid direct examination are often negative and CT or MRI to approximately 30%, with patients often displaying neuro- may be inconclusive. This delay may lead to excess mortality, par- logical sequelae. Although initial blood and cerebrospinal fluid ticularly in immunocompromised individuals. Fortunately, this samples may be negative for LM, cultures are eventually positive was not the case in our patient. thereby delaying timely diagnosis. Brain CT may be normal or Ataxic respiration during wakefulness and sleep, marked daytime alveolar hypoventilation without PHOX-2B mutation on October 1, 2021 by guest. Protected copyright. (known to cause congenital CHS1), a normal pulmonary func- tion with extreme impairment of ventilatory response to CO2, and MRI findings in our patient were consistent with a diagno- sis of acquired central hypoventilation. One aspect of our case, however, was quite unusual compared to congenital CHS: the presence of clearly defined apnoeas and hypopneas. Given the history of severe rhombencephalitis, MRI brainstem lesions were considered to be a sequel of the LM abscess. The patient’s brainstem lesions were unilateral, likely accounting for her extra- ordinary recovery. To our knowledge, this case is only the third report of LM brainstem lesions leading to acquired secondary central hypoventilation.56The course and outcome of the acquired central hypoventilation was quite different for these three patients. The two previous patients were diagnosed with the syndrome during the acute infection,56one died approxi- 5 Figure