Surgical management of anterior clinoidal meningiomas: consensus statement on behalf of the EANS skull base section.

BACKGROUND: The optimal management of clinoidal meningiomas (CMs) continues to be debated. METHODS: We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of these tumors. The data from the literature along with contemporary practice patterns were discussed within the task force to generate consensual recommendations. RESULTS AND CONCLUSION: This article represents the consensus opinion of the task force regarding pre-operative evaluations, patient's counselling, surgical classification, and optimal surgical strategy. Although this analysis yielded only Class B evidence and expert opinions, it should guide practitioners in the management of patients with clinoidal meningiomas and might form the basis for future clinical trials.

Targeting location relates to treatment response in active but not sham rTMS stimulation.

BACKGROUND: Precise targeting of brain functional networks is believed critical for treatment efficacy of rTMS (repetitive pulse transcranial magnetic stimulation) in treatment resistant major depression. OBJECTIVE: To use imaging data from a "failed" clinical trial of rTMS in Veterans to test whether treatment response was associated with rTMS coil location in active but not sham stimulation, and compare fMRI functional connectivity between those stimulation locations. METHODS: An imaging substudy of 49 Veterans (mean age, 56 years; range, 27-78 years; 39 male) from a randomized, sham-controlled, double-blinded clinical trial of rTMS treatment, grouping participants by clinical response, followed by group comparisons of treatment locations identified by individualized fiducial markers on structural MRI and resting state fMRI derived networks. RESULTS: The average stimulation location for responders versus nonresponders differed in the active but not in the sham condition (P = .02). The average responder location derived from the active condition showed significant negative functional connectivity with the subgenual cingulate (P < .001) while the nonresponder location did not (P = .17), a finding replicated in independent cohorts of 84 depressed and 35 neurotypical participants. The responder and nonresponder stimulation locations evoked different seed based networks (FDR corrected clusters, all P < .03), revealing additional brain regions related to rTMS treatment outcome. CONCLUSION: These results provide evidence from a randomized controlled trial that clinical response to rTMS is related to accuracy in targeting the region within DLPFC that is negatively correlated with subgenual cingulate. These results support the validity of a neuro-functionally informed rTMS therapy target in Veterans.

Anti-adhesion molecule strategies as potential neuroprotective agents in cerebral ischemia: a critical review of the literature.

Despite recent advances in the understanding of the pathophysiology of cerebral ischemia, current approaches attempting to prevent ischemic brain damage after an acute stroke remain quite inadequate. Today, ischemic stroke remains the third leading cause of death in industrialized nations, and the leading cause of disability requiring long term institutional care in the U.S and other industrialized nations. While one treatment, tissue plasminogen activator, has shown efficacy in clinical trials, safety concerns limit its role in clinical practice to a narrow time window of use. Acute cerebral ischemia has been shown to evoke a profound and deleterious upregulation of the inflammatory response, initiated within the cerebral microvasculature. Recently, research efforts have focused on targeting individual components of the inflammatory cascade, such as leukocyte activation and adhesion, in an attempt to develop potential neuroprotective agents. While these strategies have shown promise preclinically, clinical trials have yet to show clear benefit. Here, we review the current understanding of the pathophysiologic consequences of acute cerebral ischemic injury. Additionally, we discuss the role of the inflammatory cascade, with specific attention given to the deleterious role played by leukocyte activation and adhesion in stroke. Finally, relevant efforts to translate these basic science observations into clinical efficacy in acute stroke trials are critically reviewed.

Laser Doppler flowmetry in non-human primate stroke studies: model refinement for pre-clinical development of cerebroprotective strategies.

BACKGROUND: Safety, feasibility, and efficacy trials in non-human primate stroke models are essential to the evaluation of experimental therapies and their translation to humans. Although Laser Doppler Flowmetry has been successfully employed in rodent stroke to continuously monitor cerebral blood flow, it has not been applied in primate studies. This investigation examined the utility of Laser Doppler Flowmetry in refining an existing baboon model of cerebral ischemia/reperfusion. METHOD: Continuous Laser Doppler Flowmetry monitoring was used, in non-human primates, to document local cerebral blood flow before, during, and after middle cerebral artery territory occlusion. In each baboon (n = 7) a single Doppler probe was placed into the left frontal cortex through a precoronal burr hole. Correlations between Laser Doppler Flowmetry values and latencies to Motor Evoked Potential dropout were compared using a linear regression model. FINDINGS: Placement of the Laser Doppler probe was easily accomplished in all animals. Laser Doppler Flowmetry tracings accurately documented blood flow changes that occurred with each technical manipulation during the procedure. Laser Doppler confirmed decreased perfusion that coincided both regionally and temporally with vessel occlusion. Depth of ischemia as measured by Laser Doppler Flowmetry was associated with Motor Evoked Potential dropout latencies for individual animals. CONCLUSIONS: Continuous, single probe Laser Doppler Flowmetry is a reliable method of documenting perfusion changes following middle cerebral artery territory occlusion in a baboon model of reperfused stroke. This advanced intraoperative monitoring technique may lead to more accurate evaluation of acute stroke therapies in pre-clinical trials.