Paraneoplastic cerebellar degeneration (PCD) is a heterogeneous group of
disorders characterized by subacute cerebellar ataxia, specific tumour
types and (often) associated antineuronal antibodies. Nine specific
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 identified with a paraneoplastic
neurological syndrome and high titre (> or =400) antineuronal antibodies.
Fifty (36%) of these patients had antibody-associated 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 non-cerebellar structures occurred most frequently in
anti-Hu 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
(anti-Tr 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 five 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 significantly 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 significantly
longer [hazard ratio (HR) 0.3; 95% confidence interval (CI) 0.1-0.6; P =
0.004]. Patients > or =60 years old lived somewhat shorter from time of
diagnosis, although statistically not significant (HR 2.9; CI 1.0-8.5; P =
0.06)
