Citations

BackgroundCerebral vasogenic edema (VE) has been reported to occur during antiamyloid immunotherapy. VE may be associated with central nervous system pathology with blood–brain barrier disruptions; however, less is known about the prevalence of naturally occurring VE in patients with Alzheimer's disease (AD).MethodsFluid‐attenuated inversion recovery imaging sequences were obtained from four ongoing multicenter, randomized, double‐blind, placebo‐controlled, phase 3 trials in patients with mild‐to‐moderate AD. The first set of baseline scans was from patients in volumetric magnetic resonance imaging addenda in the Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of Amyloid PaThologY (IDENTITY) studies examining semagacestat, a γ‐secretase inhibitor (cohort 1, n = 621). The second set of baseline scans was from the EXPanding Alzheimer's Disease InvestigaTIONs (EXPEDITION) studies examining solanezumab, an anti‐Aβ monoclonal antibody (cohort 2, n = 2141). Readers were blinded to patient‐identifying information and future treatment. A third set of baseline scans was from the first 700 patients who underwent protocol‐specified magnetic resonance imaging before randomization in the EXPEDITION studies (cohort 3). The analysis used three neuroradiologists: two performed independent primary interpretations and the third was the adjudicator. Readers were blinded to patient information, treatment, protocol, and time point.ResultsFour cases of asymptomatic VE were detected at baseline/screening. Two VE cases were due to underlying extra‐axial mass lesions. The third VE case was associated with numerous microhemorrhages in keeping with cerebral amyloid angiopathy‐related inflammation or Aβ‐related angiitis. The final VE case demonstrated localized sulcal fluid‐attenuated inversion recovery imaging hyperintensity. No VE was detected in cohort 3 by readers blinded to patient baseline status.ConclusionsVE seems to be rare at baseline in patients with AD in clinical trials, 2 of 2762 associated with AD. Additional cohorts should be evaluated to support these findings.

Object Glossopharyngeal neuralgia (GPN) is a rare pain disorder characterized by severe, stabbing pain of the ear, posterior tongue, and throat. The authors report their early experience of using stereotactic radiosurgery (SRS) as an alternative to posterior fossa surgery for patients with medically resistant GPN. Methods Five patients (3 men, 2 woman) with medically resistant GPN underwent Gamma Knife surgery. The radiosurgical target was the distal portion of the glossopharyngeal and vagus nerves at the jugular foramen (glossopharyngeal meatus). The maximum radiation dose in all cases was 80 Gy. The median follow-up after radiosurgery was 13 months (range 2–19 months). Results Three patients became pain-free at 2 days, 3 days, and 2 weeks, respectively, and were able to discontinue the medications taken preoperatively for their pain. None of these patients have suffered recurrent pain since becoming pain free. Two patients experienced no benefit from the procedure and underwent posterior fossa surgery 2 and 5 months after SRS. Both of these patients continued to have pain after posterior fossa surgery. One of these patients was later discovered to have a head and neck cancer as the cause of his pain. No patient developed hoarseness or dysphagia after radiosurgery. Conclusions This preliminary experience demonstrates that SRS is an option for patients with medically resistant GPN. Additional follow-up and a larger number of patients are needed to demonstrate the long-term safety and optimal radiation dosimetry for this indication.

Background and Purpose Clinical experience has established that intravascularly placed metal coils can be a useful treatment for cerebral vascular aneurysms. However, the mechanism by which the coils induce occlusion of the aneurysm is unclear. Appropriate use of this promising treatment modality requires basic understanding of the occlusive process. We used an animal model system of experimentally induced carotid aneurysms to investigate the initial events induced by Guglielmi detachable coils (GDCs), as well as the subsequent vascular changes induced by the coils over time. Methods We induced 23 aneurysms in the carotid arteries of 16 Japanese monkeys. Nineteen aneurysms were then occluded with GDCs placed via endovascular surgery; 4 aneurysms served as controls. We then used gross and microscopic pathological examination, angiography, and scanning electron microscopy to assess the effects of the GDC. Results In the first few hours after placement of the GDC in the experimental aneurysms, we observed leukocyte attachment and deposition of fibrinlike materials and other proteins. By 4 days after coil placement, leukocytes and fibroblasts were observed in the thrombus. By 2 weeks after coil placement, there was evidence of an endothelial-like covering of the coils. At 3 months after coil placement, we observed development of an arterial media in the occluded aneurysms. Conclusions The GDCs initiated a cellular response within several hours of aneurysm occlusion. By 2 weeks after coil placement, endothelialization was proceeding, and by 3 months after occlusion, remodeling of the aneurysm had progressed to produce a media-like structure in the former aneurysm.