OMS belongs to the group of rare, immune-mediated neurologic manifestations of systemic tumors, summarized under the term paraneoplastic neurological syndromes (PNS), which develop in approximately 1 in 300 patients with cancer [9]. While the most common manifestations of PNS are limbic encephalitis (31%), cerebellar degeneration (28%) and encephalomyelitis (20%), P-OMS is significantly less frequent, with only 1% of PNS cases in a recent, representative population-based epidemiological study [9]. To account for the expanding field and detection of PNS, Graus et al. proposed a new systematization of symptoms, dividing them into ‘high-risk’ and ‘intermediate-risk’ phenotypes, and the associated antibodies into ‘high-risk’ and ‘intermediate-risk’, depending on their association with cancer (> 70% and 30–70%, respectively) [10]. Based on these characteristics, the newly introduced PNS-Care score divides the syndromes into definite, probable and possible PNS, depending on the phenotype, detected antibody and detection of a tumor on further workup [10]. Of note, among all PNS syndromes, only OMS does not require the detection of an associated antibody for the diagnosis of definite PNS, accounting for the rarity of antibodies found in OMS cases in the current literature [3].
In this patient, we describe the first case of OMS occurring in association with a pNET at an unusually young age. While paraneoplastic syndromes are a well-described complication of neuroendocrine small cell lung cancers, especially anti-Hu associated sensory neuropathy, cerebellar ataxia and encephalomyelitis [11], only a few PNS cases are reported in patients with pNET. Among these are a case of acute cerebellar dysfunction and spastic paraparesis with anti-Ri antibodies [12], an anti-GAD associated encephalomyelitis [13] and an anti-NMDA receptor encephalitis [14].
While on average, most patients with P-OMS present in patients over 50 years old, our patient was only 33 years old. In patients under 40 years of age, the most likely cause of OMS is idiopathic, post-infectious, or, in women, paraneoplastic and associated with ovarian teratoma [3, 15]. This case highlights the importance of performing a comprehensive tumor screening in patients at a younger age when OMS is present, according to the novel recommendations of the PNS care panel [10]. Had our patient’s tumor been unknown, her diagnosis could have been missed with only targeted screening for a teratoma.
Treatment of P-OMS is still mostly based on expert opinion due to the lack of prospective studies. In P-OMS, besides treatment of the underlying malignancy, first-line therapy consists of corticosteroids, intravenous immunoglobulins and plasmapheresis, similar to the treatment of autoimmune encephalitis [16]. Of note, our patient did not respond to high dose corticosteroids, but subsequently had a good therapeutic response to plasmapheresis. While systematic evidence is lacking, this case demonstrates the efficacy of plasmapheresis in steroid-refractory cases of P-OMS even in the absence of defined antibodies.
If a palliative setting had not been established, rituximab or cyclophosphamide would have been an option for second-line therapy. While the benefit of these two drugs alone or in combination has been shown in children with OMS for therapy escalation [17], no data exist for adult-onset OMS, and direct translation of the results is difficult.
Our case expands current knowledge on tumors associated with P-OMS and the age group in which it can occur, thus highlighting the importance of a comprehensive tumor evaluation in younger patients. It further adds evidence to the effectiveness of plasmapheresis in severe cases of OMS with a lack of response to first-line therapy.
