Clinical spectrum and diagnostic pitfalls of neurologic syndromes with Ri antibodies.

OBJECTIVE: To describe the main syndrome and clinical course in a large cohort of patients with anti-Ri-associated paraneoplastic neurologic syndrome (Ri-PNS). METHODS: Twenty-year retrospective nationwide study and systematic review of the literature. RESULTS: Thirty-six patients with complete clinical information were identified (median age 66 years, range: 47-87 years). In this French cohort, the majority were women (78%). At onset, 4 main patterns were observed: cerebellar syndrome (39%), isolated tremor (24%), oculomotor disturbances (17%), and other symptoms (19%). Course was multistep for 78% of cases. At the time the disease reached the plateau phase (median 12 weeks, range: 1-64 weeks; 28% >3 months), 24 (67%) showed an overt cerebellar syndrome, which was isolated in 3 patients, and was most frequently (21/24 cases) part of a multisystem neurologic disease. Patients manifested a variety of movement disorders, including myoclonus (33%), dystonia (17%), either cervical or oromandibular, and parkinsonism (17%). Most patients had cancer (92%), mainly breast cancer (n = 22). Misdiagnoses concerned 22% of patients (n = 8) and included atypical parkinsonism (n = 2), MS (n = 2), Bickerstaff encephalitis (n = 1), hyperekplexia (n = 1), vestibular neuritis (n = 1), and functional neurologic disorder (n = 1). Survival at 12 months was 73% (95% CI [0.54-0.85]), at 24 months 62% (95% CI [0.41-0.78]), and at 36 months 47% (95% CI [0.25-0.65]). There was no major clinical difference between cases retrieved from the systematic review of the literature (n = 55) and the French cohort. CONCLUSIONS: Ri-PNS is a multisystem neurologic syndrome with prominent cerebellum/brainstem involvement. Opsoclonus-myoclonus is less common than expected, and the disorder can mimic neurodegenerative diseases.

Epidemiology of paraneoplastic neurological syndromes: a population-based study.

BACKGROUND: The epidemiology of paraneoplastic neurological syndromes (PNS) remains to be defined. We present here the first population-based incidence study and report the clinical spectrum and antibody profile of PNS in a large area in Northeastern Italy. METHODS: We performed a 9-year (2009-2017) population-based epidemiological study of PNS in the provinces of Udine, Pordenone and Gorizia, in the Friuli-Venezia Giulia region (983,190 people as of January 1, 2017). PNS diagnosis and subgroups were defined by the 2004 diagnostic criteria. Age- and sex-adjusted incidence rates were calculated. RESULTS: We identified 89 patients with a diagnosis of definite PNS. Median age was 68 years (range 26-90), 52% were female. The incidence of PNS was 0.89/100,000 person-years. PNS incidence rates increased over time from 0.62/100,000 person-years (2009-2011), 0.81/100,000 person-years (2012-2014) to 1.22/100,000 person-years (2015-2017). The prevalence of PNS was 4.37 per 100,000. Most common PNS were limbic encephalitis (31%), cerebellar degeneration (28%) and encephalomyelitis (20%). Among antibody (Ab)-positive cases, most frequent specificities included: Yo (30%), Hu (26%), and Ma2 (22%), while the most frequent associated tumors were lung (17%) and breast cancer (16%), followed by lymphoma (12%). PNS developed in 1 in every 334 cancers in our region. Statistically significant associations were observed between cancer type and Ab-specificity (P < 0.001), and between neurological syndrome and Ab-specificity (P < 0.001). CONCLUSIONS: This first population-based study found an incidence of PNS that approximates 1/100,000 person-years and a prevalence of 4/100,000. Moreover, the incidence of PNS is increasing over time, probably due to increased awareness and improved detection techniques.

Stroke-Like Presentation of Paraneoplastic Cerebellar Degeneration: a Single-Center Experience and Review of the Literature.

Paraneoplastic cerebellar degeneration (PCD) is usually thought to have a subacute progression over several weeks. We report herein incidence and clinical features of hyperacute onset PCD, a vertebrobasilar stroke mimic. We performed a retrospective analysis of all suspected PCD cases referred to the Udine University Hospital between 2009 and 2017. Our center provides the only neuroimmunology laboratory for three provinces of the Friuli-Venezia Giulia region, Italy (983,190 people as of January 1, 2017). Inclusion criteria were (1) abrupt onset of neurological symptoms; (2) initial consideration of a vascular etiology; (3) final diagnosis of "definite PCD." We also carried out a systematic review of the literature in order to identify previous stroke-like PCD cases. Between 2009 and 2017, 24 patients received a final diagnosis of PCD. The age-standardized incidence rate of PCD was 0.22/100,000 person-years. Two cases (8.3%) had a stroke-like onset, with an incidence of 0.02/100,000 person-years. Additionally, 10 previously reported stroke-like PCD cases were identified. Among all cases (n = 12), 67% were female; median age was 51 years (range, 22-69). An associated cancer was discovered in all cases. Brain imaging was normal in most (75%) of the patients. Cerebrospinal fluid (CSF) analysis showed inflammatory alterations in 73% of the cases. Cancer treatment was more effective than immunotherapy in improving the neurological syndrome. Typical patients with hyperacute PCD are middle-aged women with normal brain imaging, inflammatory markers in CSF, and cancer. Surgery of the underlying cancer is probably the best treatment. PCD must be considered in the differential diagnosis of acute-onset ataxia and/or vertigo.