Normohomocysteinaemia and vitamin-treated hyperhomocysteinaemia are associated with similar risks of cardiovascular events in patients with premature atherothrombotic cerebrovascular disease. A prospective cohort study.

BACKGROUND: Mild hyperhomocysteinaemia (HHC) is associated with an increased risk of premature atherothrombotic cerebrovascular disease. We investigated the clinical efficacy with regard to the incidence of cardiovascular events of treatment of mild HHC with vitamin B(6) plus folic acid. METHODS: We studied 224 consecutive patients with clinically manifest atherothrombotic cerebrovascular disease with onset before the age of 56. Follow-up was obtained in 203 (90.6%) patients. At baseline, 52 (25.6%) were hyperhomocysteinaemic after methionine loading and started treatment with vitamin B(6) (250 mg) plus folic acid (5 mg); 151 (74.4%) were normohomocysteinaemic (reference group). RESULTS: During follow-up (median 57 months), 31 (20.5%) of the normo- and 11 (21.2%) of the hyperhomocysteinaemic patients had a new cardiovascular event. The crude incidence rate per person-year for any cardiovascular event was similar in both groups (0.043 [CI, 0.029-0.057] in the normo- vs. 0.045 [CI, 0.021-0. 069] in the hyperhomocysteinaemic group). Multivariate Cox-regression analyses showed that hypertension and cholesterol levels were associated with an increased risk of new cardiovascular events in the total group [relative risk [RR] (yes vs. no), 7.4 (3. 4-16.0) and RR (per 1 mmol/l), 1.9 (CI, 1.4-2.7)]. The adjusted RR for new cardiovascular events in the hyper- as compared to the normohomocysteinaemic patients was 0.96 (CI, 0.48-1.92). CONCLUSION: These data are consistent with a protective effect of treatment with vitamin B(6) plus folic acid in patients with premature atherothrombotic cerebrovascular disease and post-methionine HHC.

Neurotoxicity of combination chemotherapy with procarbazine, CCNU and vincristine (PCV) for recurrent glioma.

In cerebral glioma combination chemotherapy with procabazine, CCNU and vincristine (PCV) is used as adjuvant therapy in cases of recurrence. Standard PCV is usually well tolerated, but intensive PCV (CCNU 130 mg/m2 on day 1, procarbazine 75 mg/m2 on day 8-21, vincristine 1.4 mg/m2 on day 8 and 29; 6 courses every 6 weeks) is less well tolerated. We observed central neurotoxic side effects (focal neurological deficit, cognitive disturbances, slowing of EEG background activity, atrophy on cerebral MR) in combination with hematological and hepatic toxicity in four of 26 PCV treated patients with recurrent glioma. Prolonged myelo-suppression and/or ongoing (partial reversible in two patients) neurological deficit still influence daily life in three of four patients months after discontinuation of chemotherapy. Despite the fact that all four patients used anticonvulsants and have been treated with radiotherapy in the past, we have the strong impression that central neurotoxic side effects are related to intensive PCV therapy. We advocate to use the standard PCV regimen in patients with recurrent glioma, because of this potential toxicity and the lack of evidence that intensive PCV leads to better tumor control than standard PCV in cerebral glioma.