piperidines and Aneurysm--Ruptured

Impairments of memory are often found after rupture and repair of aneurysms leading to a basal forebrain lesion. This open study investigated whether cholinergic substitution therapy may be a treatment option. The effect of donepezil, a cholinesterase inhibitor on memory functions was tested in an open-label, exploratory study in 11 patients with a chronic amnestic syndrome from a ruptured and repaired aneurysm of the anterior communicating artery (seven patients), the anterior cerebral (two) or the pericallosal artery (two). Mean time since onset was 75.4 months. Memory was evaluated at baseline and consecutively after 4 weeks of 5 mg donepezil daily, 8 weeks of 10 mg donepezil, and 4 weeks after drug discontinuation. Memory functions were assessed using the California Verbal Learning Test and compared with a matched group of normal, untreated controls. Tests of attention and of executive functions were also administered. Donepezil was well tolerated. Strong group effects were found at baseline and at all follow-up measurements showing profound impairments of memory functions in the patient group. Within patient statistics showed significant improvements of short and long delay free recall scores during the treatment period, both with 5 and 10 mg donepezil daily, whereas attentional and executive functions improved only non-significantly. Memory functions decreased after drug discontinuation. Repeated test administration in the control group also showed an increase of memory scores which was minor when compared with the performance change in the patient group. Donepezil may improve episodic memory functions in patients suffering from a chronic amnestic syndrome caused by rupture and repair of aneurysms of the anterior communicating, the anterior cerebral or the pericallosal artery. Future doubled-blind, placebo-controlled trials are warranted to confirm these findings.

Topics: Adult; Amnesia; Aneurysm, Ruptured; Case-Control Studies; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Administration Schedule; Female; Humans; Indans; Male; Memory; Middle Aged; Neuropsychological Tests; Pilot Projects; Piperidines; Prosencephalon; Statistics, Nonparametric; Time Factors; Treatment Outcome

The efficacy and safety of a new platelet-activating factor receptor antagonist, E5880, were investigated for preventing cerebral vasospasm after subarachnoid hemorrhage (SAH) in 71 patients with SAH who underwent surgery for ruptured aneurysms within 3 days. Intravenous E5880 administration (300 micrograms or 1200 micrograms twice daily) was begun within 4 days and continued for 14 days. The incidence of symptomatic vasospasm, low-density area on computed tomography, and angiographic vasospasm was lower than in placebo groups in previous studies. Clinical outcome was favorable compared with previous studies. No clinically important adverse events were observed. These results suggest that E5880 is safe and effective in the treatment of patients with cerebral vasospasm due to SAH.

Topics: Adult; Aged; Aneurysm, Ruptured; Brain; Clinical Protocols; Dose-Response Relationship, Drug; Female; Humans; Incidence; Injections, Intravenous; Intracranial Aneurysm; Male; Middle Aged; Piperidines; Platelet Activating Factor; Platelet Membrane Glycoproteins; Pyridinium Compounds; Radiography; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial