SummaryParaneoplastic cerebellar degeneration (PCD) is a heterogeneous group of disorders characterized by subacute cerebellar ataxia, speci®c tumour types and (often) associated antineuronal antibodies. Nine speci®c antineuronal antibodies are associated with PCD. We examined the relative frequency of the antineuronal antibodies associated with PCD and compared the neurological symptoms and signs, associated tumours, disability and survival between groups of PCD with different antibodies. Also, we attempted to identify patient-, tumour-and treatment-related characteristics associated with functional outcome and survival. In a 12-year period, we examined >5000 samples for the presence of antineuronal antibodies. A total of 137 patients were identi®ed with a paraneoplastic neurological syndrome and high titre (b400) antineuronal antibodies. Fifty (36%) of these patients had antibodyassociated PCD, including 19 anti-Yo, 16 anti-Hu, seven anti-Tr, six anti-Ri and two anti-mGluR1. Because of the low number, the anti-mGluR1 patients were excluded from the statistical analysis. While 100% of patients with anti-Yo, anti-Tr and anti-mGluR1 antibodies suffered PCD, 86% of anti-Ri and only 18% of anti-Hu patients had PCD. All patients presented with subacute cerebellar ataxia progressive over weeks to months and stabilized within 6 months. The majority of patients in all antibody groups had both truncal and appendicular ataxia. The frequency of nystagmus and dysarthria was lower in anti-Ri patients (33 and 0%). Later in the course of the disease, involvement of noncerebellar structures occurred most frequently in antiHu patients (94%). In 42 patients (84%), a tumour was detected. The most commonly associated tumours were gynaecological and breast cancer (anti-Yo and anti-Ri), lung cancer (anti-Hu) and Hodgkin's lymphoma (antiTr and anti-mGluR1). In one anti-Hu patient, a suspect lung lesion on CT scan disappeared while the PCD evolved. Seven patients improved by at least 1 point on the Rankin scale, while 16 remained stable and 27 deteriorated. All seven patients that improved received antitumour treatment for their underlying cancer, resulting in complete remission. The functional outcome was best in the anti-Ri patients, with three out of six improving neurologically and ®ve were able to walk at the time of last follow-up or death. Only four out of 19 anti-Yo and four out of 16 anti-Hu patients remained ambulatory. Also, survival from time of diagnosis was signi®cantly worse in the anti-Yo (median 13 months) and anti-Hu (median 7 months) patients compared with anti-Tr (median >113 months) and anti-Ri (median >69 months). Patients receiving antitumour treatment (with or without immunosuppressive therapy) lived signi®-cantly longer [hazard ratio (HR) 0.3; 95% con®dence interval (CI) 0.1±0.6; P = 0.004]. Patients b60 years old lived somewhat shorter from time of diagnosis, although statistically not signi®cant (HR 2.9; CI 1.0±8.5; P = 0.06).

This study confirms the strong association between anti-Tr antibodies and PCD associated with HD. Anti-Tr antibodies from different patients recognize similar epitopes. Unlike other antineuronal antibodies, anti-Tr antibodies can be detected in the CSF but not in the serum and may spontaneously disappear during the follow-up, and Tr immunoreactivity is usually lacking in the tumor.

YM155 exhibited modest single-agent activity in patients with refractory, advanced NSCLC. A favorable safety/tolerability profile was reported. Further evaluation of YM155 in combination with chemotherapy and other targeted agents may be warranted.

Anti-CD20 monoclonal antibody (rituximab) is effectively used in the treatment of B-cell lymphomas. Recent reports in the literature suggest that antibody associated autoimmune disorders may respond to rituximab. We therefore treated nine patients with anti-Hu or anti-Yo associated paraneoplastic neurological syndromes (PNS) with a maximum of four monthly IV infusions of rituximab (375mg/m(2)). In this uncontrolled, unblinded trial of rituximab, three patients improved > or =1 point on the Rankin Scale (RS). One patient with limbic encephalitis improved dramatically (RS from 5 to 1). Further studies of rituximab in autoantibody associated PNS are warranted.