Background

A paraneoplastic neurological syndrome occurs when antibodies targeting a malignancy inadvertently react against the host nervous system. It can involve a single system or be multifocal.1 Several ‘classic’ paraneoplastic neurological syndromes have been described.2

Many other organ systems as well as the neurological system can be affected by paraneoplastic syndromes, including the endocrine, dermatological, rheumatological and haematological systems. Non-neurological paraneoplastic syndromes are more frequently encountered.3 Dermatomyositis is the most common paraneoplastic syndrome associated with nasopharyngeal carcinoma.

We report the rare case of a patient with nasopharyngeal carcinoma (NPC) presenting with anti-Ri antibody positive opsoclonus-myoclonus syndrome (OMS). We describe this patient’s clinical course and compare this with the literature.

Case presentation

A Caucasian man in his mid-50s presented by ambulance to the accident and emergency department with irregular breathing, extreme fatigue and abnormal eye movements. Four weeks previously he had received oral antibiotics for a lower respiratory tract infection from his general practitioner. He reported nausea and dizziness and received vestibular sedatives for presumed labyrinthitis. His mobility deteriorated, and he was spending most of his time in bed. One week previously, his general practitioner had noticed that his left eye was twitching and he complained of diplopia. There were abnormal facial movements and his speech was impaired.

Past medical history included hypertension and obesity. He was a non-smoker and consumed 12 units of alcohol a week.

On general observation he appeared flushed, shaky and had a stuttering voice. His temperature was 37.9°C, heart rate 70 bpm, blood pressure 147/68 mm Hg, respiratory rate 18/min and oxygen saturation 95% on air. He was alert and oriented and neurological examination found full power in all four limbs, but evidence of facial and limb myoclonus. Truncal ataxia was evident, and there were uncontrolled irregular eye movements in all directions of gaze (opsoclonus). He was found to be in severe type II respiratory failure, with admission blood gas results included in table 1. He required admission to the intensive care unit for intubation and ventilation.

Investigations

Lumbar puncture found white cell count 52 cells/µL (0–5 cells/µL) predominantly lymphocytes, protein 510 mg/L (<450 mg/L), normal glucose and unmatched oligoclonal bands. An MRI brain scan showed abnormal signals involving the brainstem, with particular involvement of the left posterior medulla and extension into the adjacent left cerebellar peduncle with no enhancement. Intravenous meropenem 2 g, clarithromycin 500 mg, and aciclovir 800 mg were initiated to treat possible infective meningoencephalitis. Other differential diagnoses included autoimmune encephalitis, Bickerstaff encephalitis, paraneoplastic syndrome and multiple sclerosis.

One day after admission he was started on a 5-day course of 500 mg IV methylprednisolone once daily, followed by immunoglobulin 0.4 g/kg per day for 5 days (adjusted for body weight) for treatment of OMS; a good response was achieved.

An onconeural antibody screen identified positive anti-Ri antibody (anti-neuronal nuclear antibody 2). Peripheral blood cultures, urine culture, bacterial meningitis screen, and respiratory virus tests were negative. Investigation results are summarised in table 1. He was ambulant and independent with activities of daily living and was discharged from hospital. He returned to driving 2 weeks later.

Outpatient Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging found a 2 cm metabolically active mass in the right nasopharynx and activity in a right retropharyngeal node (figure 1). Flexible nasoendoscopy by the otolaryngologists found an irregularity in the right nasopharynx. General anaesthetic incisional biopsy was arranged, and pathology confirmed a lymphoepithelial carcinoma, which was Epstein–Barr virus latent membrane protein-1 positive. Staging CT and MRI imaging demonstrated a T2 N1 M0 NPC.

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Figure 1

Fluorodeoxyglucose positron emission tomography/computed tomography axial head image showing a 2 cm metabolically active area in the right nasopharynx.

Differential diagnosis

Initial antibiotic and antiviral treatment was started to manage possible infective meningoencephalitis. Other differential diagnoses included autoimmune encephalitis, Bickerstaff encephalitis, paraneoplastic syndrome and multiple sclerosis.

Treatment

One month after discharge from hospital, he reported a 2-week mobility deterioration and upper limb myoclonus. Methylprednisolone 500 mg daily orally for 5 days and IVIg 100 g daily for 2 days produced a clear improvement in his mobility. The head and neck cancer multidisciplinary team discussion recommended induction chemotherapy followed by combined chemoradiotherapy treatment with curative intent. He received cisplatin 100 mg/m² and 5-fluorouracil 1000 mg/m². A lower limb deep vein thrombosis was diagnosed and managed. 5-Fluorouracil and cisplatin were given again 1 month after the first chemotherapy treatment. Due to a further 7-day episode of myoclonus, opsoclonus and vertigo, oral methylprednisolone (100 mg daily for 3 days) was required again 2 weeks later. Symptom improvement lasted only for 3 days, so further methylprednisolone 500 mg daily for 3 days was given. He had planned pretreatment gastrostomy tube insertion. Concurrent chemoradiotherapy with 3-weekly cisplatin 100 mg/m² combined with radiotherapy 70 Gy in 33 fractions over 6.5 weeks was then started. Neurological symptoms improved within 1 week of starting radiotherapy. Four months later he had returned to driving, was walking unaided and had no vertigo or oscillopsia.

Outcome and follow-up

CT imaging 3 months following treatment illustrated a good primary site response with no evidence of residual or recurrent primary site tumour. However, unfortunately multiple pulmonary metastases were identified. Second-line treatment with intravenous nivolumab 480 mg 4 weekly was then started. The risk of encephalitis was explained given the presentation with paraneoplastic neurological syndrome. He tolerated nivolumab well and received 10 cycles over 10 months.

He was admitted to hospital with respiratory distress, type II respiratory failure and reduced level of consciousness 10 days following intravenous nivolumab. Treatment for pneumonitis was started with non-invasive ventilation (bilevel positive airway pressure) and 1 mg/kg methylprednisolone and he responded well initially. There had been progressive lower limb weakness over the preceding 4 weeks. Full neurological examination found him to be oriented in time and space with fluent speech and normal cranial nerve examination. There was no opsoclonus or myoclonus. Upper limb examination was normal. Lower limb examination found normal tone, but reduced power, worse proximally, flexor plantar responses but reduced tendon reflexes. Non-radicular paraesthesia in the lower limbs was reported. There was no back pain or dysmetria and no pyramidal signs. The underlying cause of the axonal neuropathy required further investigation to ascertain if this was related to nivolumab treatment, or Guillain-Barré syndrome, or chronic inflammatory axonal polyneuropathy. An urgent CT head scan, nerve conduction studies and an MRI scan of the brain and spinal cord were requested. Lumbar puncture was not performed. Chest radiograph found prominent lung metastases. Despite the initial response to treatment, he subsequently deteriorated and active treatment was withdrawn prior to further neurological investigation. He died on day 4 of his admission.