Bilateral Vocal Cord Paralysis Associated with Meningeal Carcinomatosis from Lung Adenocarcinoma.

Cranial neuropathy is a clinical manifestation of meningeal carcinomatosis (MC); however, the glossopharyngeal and vagus nerves are rarely impaired. Therefore, dysphagia and bilateral vocal cord paralysis (BVCP) are extremely rare manifestations of MC. Here, we present a case of MC from a lung adenocarcinoma presenting with dysphagia and BVCP. An 84-year-old man with a 4-year history of left lung adenocarcinoma developed dysphagia and hoarseness. Flexible nasopharyngoscopy revealed BVCP. Ten days later, the patient developed stridor and respiratory distress. A tracheotomy was performed to prevent airway obstruction. Gadolinium-enhanced magnetic resonance imaging (MRI) of the brain showed enhancement of the bilateral glossopharyngeal and vagus nerves, and several enhancing lesions in the right internal auditory canal, left cerebellum, fourth ventricle, pons, cerebral aqueduct, and right frontal lobe, suggesting MC and brain metastasis. Based on the clinical history of malignancy and the MRI findings, the patient was diagnosed with MC. As the patient refused additional treatment, including chemotherapy and radiation, only palliative care was provided. To the best of our knowledge, this was the first case of MC from a solid tumor presenting with BVCP. When patients with malignancy present with BVCP, MC should be considered.

Introduction

Meningeal carcinomatosis (MC) occurs in 3%–5% of all cancer patients [1]. It is associated with a poor prognosis, with a median survival time of 2–3 months. Malignant cells that commonly originate from breast cancer, lung cancer, melanoma, and lymphoid malignancies infiltrate cerebrospinal fluid through the bloodstream or by perineural dissemination along peripheral nerves and spread to the brain, cranial nerves, and spinal cord [2]. Cranial neuropathy is a clinical manifestation of MC [3]. The optic nerve, oculomotor nerve, trochlear nerve, abductor nerve, facial nerve, and auditory nerve are frequently involved [2, 4, 5]. Dysphagia and vocal cord paralysis represent unusual manifestations and only one case report of dysphagia and bilateral vocal cord paralysis (BVCP) due to MC has been reported [6]. The patient had a malignant lymphoma. No other cases of solid tumors have been reported. Herein, we report the first case of MC from a lung adenocarcinoma presenting with dysphagia and BVPC.

Case Report/Case Presentation

An 84-year-old man with a 4-year history of left lung adenocarcinoma underwent chemotherapy with vinorelbine 4 months prior. The patient had undergone radiotherapy and chemotherapy with gefitinib, carboplatin combined with pemetrexed, and atezolizumab. Despite these treatments, the lung adenocarcinoma gradually metastasized to the right lung, left adrenal gland, and the 8th thoracic spine. Around 4 months after the initiation of vinorelbine, the patient acutely developed dysphagia and hoarseness. Four days later, he visited our hospital. The patient did not have a headache, dyspnea, hearing loss, or tinnitus. On physical examination, inspiratory stridor was not present. The patient was admitted to our hospital for further investigation. Neurological examination revealed hoarseness, reduced gag reflex, soft palate paralysis on both sides, and hyporeflexia. Ophthalmoplegia, ptosis, muscle weakness, sensory impairment, ataxia, rigidity, or tremor were not observed. On flexible nasopharyngoscopy, bilateral vocal cord adduction was moderately restricted during phonation, and bilateral vocal cord abduction was severely restricted during inspiration (Fig. 1). During the endoscopic evaluation of swallowing, the pharyngeal phase of swallowing was impaired (online suppl. Video 1; for all online suppl. material, see www.karger.com/doi/10.1159/000524323). The intravenous administration of edrophonium (10 mg) did not improve hoarseness and dysphagia. The laboratory test results were as follows: serum C-reactive protein, 28.8 mg/dL (0.0–0.3 mg/dL); serum angiotensin-converting enzyme, 9.9 U/L (7.0–25.0 U/L); serum carcinoembryonic antigen, 185.8 ng/mL (0.0–5.0 ng/mL); and HbA1c, 6.1% (4.6–6.2%). The anti-nuclear, anti-acetylcholine receptor, anti-MuSK, and anti-ganglioside antibodies were all negative. Gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) revealed several enhancing lesions in the bilateral glossopharyngeal and vagus nerves, right internal auditory canal (IAC), left cerebellum, fourth ventricle, pons, cerebral aqueduct, and right frontal lobe (Fig. 2). These lesions were suggestive of MC and brain metastasis [4]. Although gadolinium-enhanced T1-weighted MRI was performed 3 years ago to determine the stage of lung adenocarcinoma, these lesions were not shown. Upon neck and chest computed tomography, no lesion causing vagus nerve paralysis around the aortic arch, right subclavian artery, or cervical neck was noted (Fig. 3). As the patient refused lumbar puncture for fear of pain, cerebrospinal fluid cytology was not performed. As lung adenocarcinoma is one of the most common causes of MC [5], based on these clinical and radiological findings, the patient was diagnosed with MC. Ten days after admission, intratracheal intubation was performed because the patient acutely presented with stridor, dyspnea, and respiratory distress. Intratracheal intubation was uncomfortable, even under optimal sedation, and tracheotomy was subsequently conducted. After being informed about the diagnosis and prognosis, the patient did not desire additional treatment, including chemotherapy and radiotherapy. One month later, the dysphagia and hoarseness persisted. On follow-up flexible nasopharyngoscopy, the bilateral tensionless vocal cords were passively abducted during phonation and fixed in the median position during inspiration (Fig. 1). The paradoxical vocal cord movement indicated a more severe vocal cord paralysis than that on admission. Two months after admission, the patient was transferred to another hospital for palliative care.

Fig. 1

Flexible nasopharyngoscopy. Bilateral vocal cords during phonation (a) and inspiration (b), upon admission. Bilateral vocal cords during phonation (c) and inspiration (d), 1 month later. c The glottis shows an oval appearance during phonation.

Fig. 2

Gadolinium-enhanced MRI of the brain. Gadolinium-enhanced T1-weighted MRI shows thickening and enhancement of the bilateral vagus nerve and glossopharyngeal nerve (a), and contrast-enhancing masses in the right IAC (b), left cerebellum (c), pons and fourth ventricle (d), cerebral aqueduct (e), and in the right frontal cortex (f).

Fig. 3

a–c Neck and chest CT. The neck and chest CT shows no lesion causing bilateral vagus nerve paralysis. b A mass lesion is observed in the left lung, representing primary lung adenocarcinoma.

Discussion/Conclusion

This is the first report of MC from a solid tumor presenting with dysphagia and BVCP. Although we could not perform a cerebrospinal fluid test, a history of advanced lung adenocarcinoma and neuroimaging features would support the diagnosis of MC. In a previous study, the rate of positive cytological results in the cerebrospinal fluid test was high in patients with leptomeningeal enhancement, superficial cerebral lesions, cranial nerve enhancement, and communicating hydrocephalus [4]. Although these imaging features may be associated with other neurological disorders, those are strongly associated with MC. However, it was difficult to distinguish whether the superficial cerebral lesions were parenchymal, meningeal, or both. In MC, 31% of patients were reported to have brain metastases [4]. In the present case, a mass lesion was observed in the right IAC with a size of 5.8 mm × 8.6 mm. Although IAC metastasis was strongly suspected, the possibility of vestibular schwannoma could not be ruled out completely. However, lung adenocarcinoma is a common cause of brain metastasis. In general, the average growth rate of vestibular schwannoma is 0.99–1.11 mm/year. As the mass lesion appeared within 3 years, the present size could not be explained by vestibular schwannoma. Although the patient did not have hearing loss or facial paralysis, some patients with unilateral IAC metastasis had no associated symptoms [7, 8].

Common causes of dysphagia and BVCP include myasthenia gravis, Guillain-Barré syndrome, multiple systemic atrophy, amyotrophic lateral sclerosis, and diabetic cranial neuropathy. In the present case, these neurological disorders were ruled out based on the medical history, neurological examination, laboratory tests, and radiological findings. MC is an unusual cause of dysphagia and BVCP. In a previous report, only 6 out of 122 patients with lung cancer presented with bucking and dysphagia. In another report, 2 out of 76 patients with solid tumors presented with vagus neuropathy. There has been only one reported case of dysphagia and BVCP due to MC [9]. A previously reported case represents a 74-year-old man with diffuse large B-cell lymphoma. Although the detailed mechanism remains uncertain, the glossopharyngeal and vagus nerves may have a lower affinity for cancer cells. In the present case and the previous case, dysphagia acutely appeared, followed by the subsequent development of airway obstruction due to BVCP within 2 weeks. Clinical characteristics in both cases represent acute-onset bilateral glossopharyngeal and vagus nerve involvement. Acute onset bilateral cranial neuropathy is common in MC. Four cases of acute onset bilateral optic neuropathy [10, 11, 12], 2 cases of acute onset bilateral auditory neuropathy [13, 14], and one case of acute-onset bilateral facial nerve paralysis as the manifestation of MC have been reported [15]. Acute-onset bilateral cranial neuropathy might be a characteristic feature of MC. Moreover, gadolinium enhancement and thickening of the bilateral vagus nerve and glossopharyngeal nerve were radiologically similar in the present and the previous cases. Progressive neurological deterioration may reflect ongoing axonal destruction and vascular compromise secondary to neoplastic infiltration of the glossopharyngeal and vagus nerves. In conclusion, when patients with malignancy acutely present with dysphagia and BVCP, MC should be considered.

Statement of Ethics

Ethical approval is not required for this study in accordance with local guidelines. Written informed consent was obtained from the patient's next of kin for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding was received for this study.

Author Contributions

Gohei Yamada designed the study, analyzed the data, and drafted the manuscript. Takanari Toyoda, Eiichi Katada, and Noriyuki Matsukawa analyzed the data and revised the manuscript for intellectual content.

Data Availability Statement

Data are included in the manuscript. Further inquiries can be directed to the corresponding author.

Supplementary data

Click here for additional data file.

Supplemental Video

Click here for additional data file.