Central sleep apnea as an initial presentation of small cell lung carcinoma with anti‐Hu antibody‐related paraneoplastic neurologic syndrome

Abstract

Anti‐Hu antibody‐related paraneoplastic neurologic syndrome (PNS), a rare disease primarily associated with small cell lung carcinoma, is characterized by diverse neurologic manifestations. Central sleep apnea, although rare, is specific to anti‐Hu antibody‐related PNS. Herein, we present a case of out‐of‐hospital cardiac arrest attributed to hypercapnic central sleep apnea and detail the subsequent workup that revealed anti‐Hu brainstem encephalitis. A malignancy survey revealed mediastinal small cell carcinoma. The patient was treated by tumour excision, chemotherapy, plasma exchange, and high‐dose glucocorticoids. Though the neurologic damage caused by anti‐Hu antibody was documented to be relatively irreversible in literatures, such hypercapnic central sleep apnea resolved in our case about 1 month later.

We present a case of out‐of‐hospital cardiac arrest (OHCA) attributed to hypercapnic central sleep apnea and detail the subsequent workup that revealed anti‐Hu brainstem encephalitis. A malignancy survey revealed mediastinal small cell carcinoma.

INTRODUCTION

Anti‐Hu antibody‐related paraneoplastic neurologic syndrome (PNS), a rare disease primarily associated with small cell carcinoma, is characterized by diverse neurologic manifestations. Central sleep apnea, although rare, is specific to anti‐Hu antibody‐related PNS. Here, we present a case of out‐of‐hospital cardiac arrest (OHCA) attributed to hypercapnic central sleep apnea and detail the subsequent workup that revealed mediastinal small cell carcinoma.

CASE REPORT

A 72‐year‐old male patient presented to our hospital with OHCA with a non‐shockable rhythm. Prior to the event, he was administered alprazolam (0.5 mg) and subsequently fell asleep. His family found him unresponsive and in cardiac arrest. An emergency medical technician performed cardiopulmonary resuscitation for 22 min and subsequently intubated the patient. Return of spontaneous circulation (ROSC) was achieved immediately after intubation. The initial workup did not reveal an obvious cause for the cardiac arrest other than prominent hypercapnia. The patient became fully conscious after ROSC. Subsequently at our hospital, we performed a spontaneous breathing trial and successfully weaned the patient off mechanical ventilation. However, during admission, he experienced in‐hospital cardiac arrest after falling asleep, and we were able to achieve ROSC after prompt intubation and mechanical ventilation. Repeated evaluation revealed prominent hypercapnia up to 101.5 mmHg PaCO2. We noticed central apnea during sleep; however, full consciousness without apnea was observed when the patient was awake. Central sleep apnea was diagnosed observing obvious apnea when turning the respiratory rate to 0.5 times per minute by pressure‐controlled ventilation mode, while obstructive sleep apnea is not possible in an intubated patient. The neurological evaluation did not reveal muscle weakness, cranial nerve abnormalities, or sensory defects; however, the patient reported a subacute progressive oropharyngeal dysphagia for about 1 month. Brain magnetic resonance imaging (MRI) revealed the absence of structural lesions in the pons and medulla, whereas chest computed tomography revealed a 3.2‐cm middle mediastinal mass (Figure 1). Considering the mediastinal mass, absence of brainstem lesions on brain MRI, and characteristic presentation of Ondine's curse, we suspected that the patient had anti‐Hu encephalitis. Cerebrospinal fluid analysis revealed the absence of pleocytosis and glucose consumption, but total protein levels increased up to 59 mg/dL. The PNS panel revealed elevated titers of anti‐Hu antibodies in both the serum and cerebrospinal fluid. Therefore, we diagnosed the patient with anti‐Hu antibody‐related brainstem encephalitis. We treated the patient using high‐dose prednisolone (40 mg/day) and performed plasma exchange five times every other day for anti‐Hu PNS. A cardiothoracic surgeon performed an excisional biopsy of the mediastinal mass, and the final pathology revealed small cell carcinoma, which is the most common underlying malignancy of anti‐Hu PNS. We treated the patient with a reduced‐dose of etoposide and platinum for small‐cell cancer of the mediastinum. The dose of the prednisolone was then tapered gradually in 1 month to 10 mg/day as a long‐term maintenance therapy, and the patient utilized a home ventilator via tracheostomy during sleep. Approximately 1 month later, the patient was readmitted with necrotizing pneumonia caused by Pseudomonas aeruginosa. Surprisingly, the patient's central respiratory drive recovered, at least partially, which was documented using the ventilator.

FIGURE 1.

The chest computed tomography revealed a 3.2 cm mediastinal mass.

DISCUSSION

The possible localization of hypercapnic central sleep apnea includes lower brainstem, reticulospinal tract, and neuromuscular junction (NMJ) disorders as well as myopathies. ¹ In our case, the full muscle power and intact active respiratory drive during the awake state indicated preserved corticospinal tract, NMJ, and muscle functions. Therefore, in our case, the neurological localization was assumed to be at the lower brainstem.

The differential diagnosis of Ondine's curse in such situations includes congenital central hypoventilation syndrome (CCHS), developmental diseases such as Leign syndrome, degenerative diseases such as multiple system atrophy, brainstem tumours, Wallenberg syndrome, and anti‐Hu PNS. ¹ Owing to the age of onset, CCHS and developmental diseases were unlikely, and the absence of brain MRI abnormalities in the brainstem ruled out the possibilities of degenerative diseases, brainstem tumours, and Wallenberg syndrome. In addition to the mediastinal mass, we suspected anti‐Hu PNS.

PNS is a rare but complex condition characterized by various antibodies, clinical manifestations, and associated malignancies. Various neurological manifestations of anti‐Hu PNS occur with other PNS antibodies; however, only central sleep apnea is unique to anti‐Hu antibody. ²

We diagnosed the patient based on the clinical manifestations, laboratory evidence, and malignancies consistently associated with such symptoms or antibodies. The definite diagnosis of PNS can be established with a PNS care score >8. ² In our case, the PNS care score was 9; therefore, the diagnosis was confirmed.

Small cell lung carcinoma is the most common underlying malignancy associated with anti‐Hu antibodies; however, neuroendocrine tumours of other locations, such as the mediastinum, prostate, pancreas, or gastrointestinal tract, are also possible. ³ Prompt identification of PNS is crucial because it may cause irreversible and progressive disability. Treatment options include cancer‐directed and immunosuppressive therapies.

Immunoglobulins against intracellular antigens, including anti‐Hu antibody, usually cause T‐cell‐mediated irreversible neuronal loss. ⁴ Therefore, we initially predicted that hypercapnic central sleep apnea would be irreversible. However, prompt administration of cancer treatment and immunosuppressive therapy seemed to halt immune dysregulation and facilitate neural regeneration.

AUTHOR CONTRIBUTIONS

Yi‐Tse Su and Chin‐Wei Kuo searched the literature; Yi‐Tse Su and Jen‐Chieh Lee wrote the manuscript. All authors contributed to and approved the final manuscript.

CONFLICT OF INTEREST STATEMENT

None declared.

ETHICS STATEMENT

The authors declare that appropriate written informed consent was obtained for the publication of this manuscript and accompanying images.

Su Y‐T, Kuo C‐W, Lee J‐C. Central sleep apnea as an initial presentation of small cell lung carcinoma with anti‐Hu antibody‐related paraneoplastic neurologic syndrome. Respirology Case Reports. 2024;12(12):e70079. 10.1002/rcr2.70079

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.