Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy

Abstract

In a retrospective study, we determined clinical and serological findings, associated tumours, outcome and prognostic factors in 73 Hu-Ab positive patients detected in a Dutch reference laboratory. The most frequent signs and symptoms at presentation were sensory neuropathy (55 %), cerebellar degeneration (22 %), limbic encephalitis (15 %) and brainstem encephalitis (16 %). 23 % developed autonomic dysfunction including gastro-intestinal motility disorders in 14 %. In 85 % a tumour was detected, which was a lung tumour in 77 %. Signs, symptoms and associated tumours did not differ in six patients with additional neuronal antibodies (anti-amphiphysine, anti-CV2, anti-Ri). The overall 3 months, one-year and three-year survival rates from the time of diagnosis were 64 %, 40 % and 22 %. Rankin Scale Score (RS) at diagnosis and presence of tumour at the time of diagnosis predicted mortality with hazard ratios (95 % CI) of 2.6 (1.5-4.6) and 1.5 (1.1-2). The median delay between onset of symptoms and Hu-Ab diagnosis was 4 months. There was a negative association between delay RS at diagnosis (P=0.03). In a logistic regression analysis, only older age (OR=0.15; 0.02-0.63) and a higher RS at diagnosis (OR=0.29; 0.11-0.73) were associated with a lower probability of successful functional outcome. Adjusted for these factors, antitumour therapy showed a higher but statistically not significant probability of successful outcome (OR=3.5; 0.87-14.3). Our study underlines the importance of early diagnosis and start of antitumour treatment when the patient is still in a better functional state. The delay between onset of symptoms and diagnosis of PEM/SN suggests a window for improving outcome in these patients.

Paraneoplastic syndromes of the peripheral nerves

“…However, a wide variety of cancers may be associated with SSN, including prostate, breast, pancreatic, neuroendocrine, bladder, and ovarian cancer [5,32,[37][38][39]. Typically, the neuropathy predates the discovery of the cancer by 3-8 months [5,38,40]. In a patient in cancer remission, the development of a syndrome suggestive of a PND may herald tumor recurrence [40].…”

Paraneoplastic Neurologic Disorders in Children

“…Corticosteroids, IVIG, and plasma exchange may be helpful in some disorders but were found not to be helpful in a large study of adults with anti-Hu encephalitis or encephalomyelitis [36,45]. Improvement with rituximab has been reported in two patients with anti-Hu antibodyassociated encephalomyelitis [46].…”

Bilateral Tonic Pupils with Evidence of Anti-Hu Antibodies as a Paraneoplastic Manifestation of Small Cell Lung Cancer

“…Small cell lung cancers are more often associated with paraneoplastic disorders. In anti-Hu-positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy, a lung tumour was detected in 77% of cases [13]. The therapy of paraneoplastic syndromes remains difficult and controversial.…”