Several
cancers, especially lung, ovarian and breast, can cause
paraneoplastic cerebellar degeneration. The presence of different antineuronal
antibodies associated with different
cancers and
paraneoplastic cerebellar degeneration suggests that several immunological mechanisms may result in the same
neurological disorder. In patients with
small-cell lung cancer,
paraneoplastic cerebellar degeneration may occur with or without Hu antineuronal
antibodies (HuAb), indicating that patients with the same tumour can develop
paraneoplastic cerebellar degeneration by different immunological mechanisms. Furthermore,
paraneoplastic cerebellar degeneration sometimes occurs in association with the
Lambert-Eaton myasthenic syndrome. In order to try to understand the clinical implication of antineuronal
antibodies in patients with
small-cell lung cancer, we examined the serum of 57 patients with presenting symptoms of
paraneoplastic cerebellar degeneration for the presence of HuAb and P/Q- and N-type voltage-gated
calcium channel antibodies. Patients with
paraneoplastic cerebellar degeneration who were HuAb positive were compared with HuAb negative patients with respect to neurological symptoms, course of the
neurological disorder, response to treatment, tumour prognosis, pathological findings, and cause of death. The tumour outcome and serological findings of these patients were also compared with those of 109
small-cell lung cancer patients without
paraneoplastic syndromes of the CNS. Titres of HuAb were classified as 'high' (immunoblot titre > 1:10,000) or 'low' (< 1:10,000), the latter similar to the antibody titres detected in some
small-cell lung cancer patients without paraneoplastic symptoms. Twenty-five patients with
paraneoplastic cerebellar degeneration (44%) had high titres of HuAb, four (7%) had low titres of HuAb, and 28 (49%) were HuAb negative; for clinical comparisons with the patients with high titres of HuAb, the four patients with low antibody titres were included in the HuAb negative cohort. None of the 109
small-cell lung cancer patients without paraneoplastic symptoms had high titres of HuAb. The presence of high titres of HuAb defined a subset of patients who differed from the HuAb negative
paraneoplastic cerebellar degeneration cohort, HuAb positive patients were more likely to be female (P < 0.01), to have multifocal neurological disease (brainstem
encephalopathy and sensory neuropathy being common extracerebellar manifestations) (P < 0.002), and be severely disabled (P < 0.005). A total of nine patients (16%) from both
paraneoplastic cerebellar degeneration groups developed electrophysiologically confirmed
Lambert-Eaton myasthenic syndrome. Seven of these nine patients had serum available for P/Q-type voltage-gated
calcium channel antibody testing and all seven were positive. In addition, 20% of HuAb negative
paraneoplastic cerebellar degeneration patients without clinically identified
Lambert-Eaton myasthenic syndrome had P/Q-type voltage-gated
calcium channel antibodies, while only 2% of
small-cell lung cancer patients without paraneoplastic symptoms had these
antibodies. Treatment of the tumour and/or
immunomodulation did not alter the course of
paraneoplastic cerebellar degeneration, but improved
Lambert-Eaton myasthenic syndrome symptoms. At the time of death, in 60% of HuAb positive and 20% of HuAb negative
paraneoplastic cerebellar degeneration patients, the tumour was either not evident or localized to the chest (P < 0.007); neurological disease was the cause of death of 65% HuAb positive
paraneoplastic cerebellar degeneration and 10% HuAb negative
paraneoplastic cerebellar degeneration patients (P < 0.001). (ABSTRACT TRUNCATED)