Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial.

BACKGROUND: Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma. METHODS: In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated. RESULTS: The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log10CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log10CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated with OS. CONCLUSION: CEC numbers increased during treatment with bevacizumab plus lomustine but not during treatment with either agent alone, suggesting that this combination induced the greatest vascular damage. Although the absolute number of CECs was not associated with OS in patients treated with bevacizumab either alone or in combination, they could serve as a marker in glioblastoma patients receiving lomustine single agent.

Incidence of central nervous system involvement in chronic lymphocytic leukemia and outcome to treatment.

Leptomeningeal involvement in patients with CLL is relatively rare and the prognosis is usually considered to be poor. The authors reviewed all CLL patients treated in a tertiary referral center to assess the incidence and outcome of leptomeningeal involvement (LI) in CLL. They found an incidence of 1-2% of LI. Most of the patients with LI had a longterm survival, despite failure to clear the cerebrospinal fluid from tumor cells.

Recovery of posterior communicating artery aneurysm-induced oculomotor palsy after coiling.

BACKGROUND AND PURPOSE: Recovery of oculomotor (cranial nerve [CN] III) palsy after surgery of posterior communicating artery (PcomA) aneurysms has been well documented, but recovery after coiling is poorly understood. In this study, we report the recovery after coiling of PcomA aneurysm-induced CN III palsy in 21 patients at follow-up of 1 to 7 years. MATERIALS AND METHODS: Of 135 patients with a PcomA aneurysm treated with coils between January 1997 and December 2003, there were 21 patients with initial CN III dysfunction who were selected and reevaluated. There were 2 men and 19 women with a mean age of 54.9 years. In 17 patients, CN III palsy was associated with subarachnoid hemorrhage (SAH). Timing of treatment after onset of symptoms was 1 to 3 days in 5 patients, 4 to 14 days in 13, and more than 14 days in 3. Mean size of the aneurysm was 9 mm. Initial CN III palsy was complete in 15 patients and partial in 6. Mean follow-up after coiling was 3.7 years (range, 1-7 years). RESULTS: Of 15 patients with initial complete CN III palsy, recovery was complete in 3 and partial in 10. In 2 patients, complete CN III palsy was unchanged. Of 6 patients with initial partial CN III palsy, recovery was complete in 5 and partial in 1. Initial partial CN III palsy was the only predictor of complete recovery at follow-up. CONCLUSION: PcomA aneurysm-induced CN III palsy improves or cures after coiling in most patients. Complete recovery is more likely with initial partial dysfunction of the nerve.

Antisaccadic effects of a dopamine agonist as add-on therapy in advanced Parkinson's patients.

We wanted to compare clinical neurological and antisaccadic behavior before and after addition of a dopamine agonist to the usual antiparkinsonian drugs in advanced Parkinson's disease. Parkinson's patients in stage 3 and 4 of Hoehn and Yahr not yet taking a dopamine agonist were selected. In 20 patients, the treating neurologist decided to add pergolide. The dose of pergolide was adjusted by the treating neurologist according to clinical response. Antisaccades were studied by infrared oculography before and after addition of pergolide. Antisaccades are voluntary saccades in the opposite direction of an unanticipated visual target. The patients made more errors, i.e. they glanced to the target or they made no eye movement at all. In contradistinction to the global neurological improvement and the better motor scores, antisaccadic disturbances did not improve significantly with pergolide, except in younger patients. These findings suggest that antisaccadic alterations in patients with advanced Parkinson's disease could be multifaceted. Not only depletion of dopamine, but also non-dopaminergic dysfunctions could contribute. Cortical frontal lesions must also be taken into account.

Antisaccades and remembered saccades in mild traumatic brain injury.

The most common site of focal lesions after mild traumatic brain injury (MTBI) is the frontal lobe. This lobe, however, is difficult to examine clinically. Neuroimaging is not performed routinely and usually shows normal results in uncomplicated trauma. Antisaccades (AS) and remembered saccades (RS) are neuro-ophthalmological tests of frontal function. This study examined whether there are disturbances of latency time or error rate of AS and RS in patients within 24 h after MTBI. Eye movements were studied with infrared-oculography. Data were obtained prospectively from 25 patients. An additional group of 6 patients with MTBI and alcohol intoxication were also examined. No statistical differences in AS or RS, either for errors or for latency time, were found between a group of age-matched controls and the patients, except in the group of alcohol-intoxicated MTBI patients. Our findings indicate that visual reflex inhibition and initiation of voluntary saccades were not disturbed in the nonintoxicated patients. It is hypothesized that the responsible frontal area was not affected. It is concluded that error rate and latency time of AS and RS are inappropriate measures for evaluating acute MTBI.