Benign opsoclonus myoclonus syndrome and prostate cancer

Dear Editor:

Paraneoplastic syndromes (PNS) are clinical syndromes associated with cancer, and may coincide with diagnosis of the cancer or precede it, sometimes by several years. The neoplasms most frequently presenting PNS are small-cell lung cancer and gynaecological tumours; association with urological cancers is much rarer. Within the group of urological cancers, the type most commonly associated with PNS is kidney cancer, whereas presentation with prostate cancer is extremely rare.¹ Very few cases are reported of opsoclonus myoclonus syndrome (OMS) associated with prostate cancer, and prognosis was poor in all known cases. We present a case of OMS presenting synchronously with prostate adenocarcinoma with bone metastases, with benign progression of the PNS.

Clinical case: the patient was a 69-year-old man with a history of arterial hypertension and diabetes; he smoked 3 cigars per day and was under study for an elevated prostate specific antigen level of 14 IU. He attended our hospital's emergency department due to inability to walk. Symptoms began as mild instability, rapidly progressing to severe ataxia. Physical examination found rapid, involuntary, conjugate saccades in both eyes on the horizontal plane only, compatible with ocular flutter. The patient presented generalised, arrhythmic, asynchronous myoclonus of the limbs, trunk, and abdomen. Gait and truncal ataxia were observed. Results from a complete blood count, biochemical testing, serology study, and immune profile were normal. Tests for tumour markers, onconeuronal antibodies, and surface antigen antibodies (anti-Hu, Yo, Ri, Zic, CRMP5, Ma, and Tr) yielded negative results. A chest, abdomen, and pelvis CT scan revealed no abnormalities. Prostate biopsy revealed small acinar adenocarcinoma. Bone scintigraphy showed osteoblastic lesions in the left hemipelvis. A PET-CT study ruled out underlying neoplasia. The patient was treated with high-dose steroids and hormonal therapy, and symptoms resolved completely at one year after onset.

Graus et al.² include OMS among the group of classical PNS and classify its association with a tumour as a definite PNS, with diagnosis not being ruled out by the absence of onconeuronal antibodies, as was the case in our patient. Storstein et al.³ report the largest series of PNS associated with prostate cancer (n = 37), observing that the 3 most frequent syndromes were paraneoplastic cerebellar degeneration, limbic encephalitis/encephalomyelitis, and subacute sensory neuronopathy. In a literature search, we identified only 4 cases of OMS associated with prostate cancer. Three of these cases consisted of saccadic oscillations on the horizontal plane only, as in our patient. In 2 of the cases reported by Baloh et al.,⁴ the patients developed alterations in ocular motility and gait after diagnosis of prostate cancer, as well as muscle spasms. In both cases, post mortem examination detected perivascular chronic inflammatory cell infiltration in the paramedian pontine reticular formation. The identification of new antibodies against neuronal cell surface antigens, specifically those targeting the glycine receptor (which is involved in neurotransmission in omnipause neurons of the paramedian pontine reticular formation), and the presence of this molecule in oat-cell carcinoma cells have opened several hypotheses that may explain the association between both processes.⁵ The third patient reported was a man with prostate cancer who presented a brainstem paraneoplastic syndrome and altered ocular motility on the horizontal plane; an antibody targeting intraneuronal antigens was detected, but the antigenic target could not be identified.¹ In the fourth case, reported by Nasri et al.,⁶ the patient was diagnosed with metastatic prostate cancer, and 18 months later developed OMS with onconeuronal antibodies (anti-Hu and anti-Yo) coinciding with a lung mass that was compatible with oat cell tumour according to anatomical pathology findings. In our patient, we suspected that the neurological symptoms may be explained by a second neoplastic process, but ruled out this possibility after laboratory and imaging studies.

The diagnosis of definite PNS is further supported by the resolution of symptoms at one year of follow-up.²

In conclusion, we present an extremely rare association between a classical PNS and a cancer presenting high incidence and prevalence, with such a favourable progression that we may suggest greater optimism in the diagnosis and prognosis of these patients.