Archives of neurology最新文献

Objectives: To describe a case and review literature for intracerebral hemorrhage caused by migraine.

Design: Case report.

Setting: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Patient: A 54-year-old truck driver with a 2-year history of atypical headaches.

Results: A 54-year-old right-handed truck driver was seen in consultation with a 2-year history of atypical headaches.The headaches were dull, throbbing, gradually progressive,and limited over the left occipital area. They were accompanied by right visual field deficit, diplopia, and,at times, confusion. These headaches were notably different from the usual migraine headaches he had been having for more than 20 years. Brain imaging revealed left parieto-occipital lobar hemorrhage. Further investigations ruled out arteriovenous malformations. He did not have any vascular risk factors, including hypertension. Migraine-associated intracerebral hemorrhage was considered to be the most likely diagnosis.

Conclusions: Intracerebral hemorrhage associated with migraine is believed to result from vasoconstriction leading to ischemia of the walls of blood vessels, making them leaky and porous. It is important to be aware of this phenomenon because vasoactive medications used to treat migraine can further aggravate the vasoconstriction and hence the intracerebral bleed.

Background: Few data are available on the relationship between fluid-attenuated inversion recovery vascular hyperintensities and proximal middle cerebral artery occlusion prognosis.

Objectives: To assess a fluid-attenuated inversion recovery vascular hyperintensities score (FVHS) and explore its relationship with recanalization status and clinical outcomes after intravenous thrombolysis.

Design: Retrospective study.

Setting: Stroke unit in a university hospital.

Patients: Consecutive patients with proximal middle cerebral artery occlusion, thrombolysed within 6 hours, were selected from our prospective database. The FVHS (range,0-10; divided into low, medium, and high thirds) was quantified on the magnetic resonance image obtained at admission. Recanalization rates, infarction size (Alberta Stroke Program Early CT Score applied to diffusion weighted imaging [ASPECTS-DWI]), and 3-month functional outcomes (modified Rankin Scale score) were determined. Poor outcomes and large infarctions were defined as a modified Rankin Scale score higher than 2and an ASPECTS-DWI score of 5 or lower, respectively.

Main outcome measures: Interaction among FVHS,recanalization status, and outcomes.

Results: Thirty-four patients had a low FVHS (4), 32 had a medium FVHS (5 or 6), and 39 had a high FVHS (≥7). The rate of poor functional outcome (modified Rankin Scale score >2) was higher for the group with low FVHSs than those with medium FVHSs and high FVHSs(82.3% vs 43.7% and 43.5%, respectively; P.001). Therate of 24-hour large infarctions(ASPECTS-DWI score 5)was higher for those with low FVHSs than those with medium and high FVHSs (88.2% vs 56.2% and 51.3%, respectively;P=.002). The recanalization rate was not associated with FVHS. Multivariate analysis retained low FVHS as an independent early predictor of poor clinical outcome (odds ratio=9.91; 95% CI, 2.01-48.93; P=.004)and large infarction (odds ratio=6.99; 95% CI, 1.78-27.46; P=.005).Low FVHS remained associated with poor outcomes regardless of recanalization status. Early recanalization in patients with a low FVHS decreased the poor functional outcome rate from 100% to 64.7% (P=.02).

Conclusions: The FVHS is an early independent prognostic marker for patients with proximal middle cerebral artery occlusion. Synergy between FVHS and recanalization status appears to be a critical determinant of final outcomes, supporting intensive reperfusion treatment for patients with a low FVHS.

Objective: To assess the safety, tolerability, and pharmacokinetic and pharmacodynamic effects of the -secretase inhibitor avagacestat in patients with mild to moderate Alzheimer disease (AD).

Design: Randomized, double-blind, placebo-controlled,24-week phase 2 study.

Setting: Global, multicenter trial.

Patients: A total of 209 outpatients with mild to moderate AD were randomized into the double-blind treatment phase. The median age of the patients was 75 years,58.9% were APOE ε4 carriers, and baseline measures of disease severity were similar among groups.

Intervention: Avagacestat, 25, 50, 100, or 125 mg daily,or placebo administered orally daily.

Main outcome measures: Safety and tolerability of avagacestat.

Results: Discontinuation rates for the 25-mg and 50-mg doses of avagacestat were comparable with placebo but were higher in the 100-mg and 125-mg dose groups.Trends for worsening cognition, as measured by change from baseline Alzheimer Disease Assessment Scale cognitive subscale score, were observed in the 100-mg and125-mg dose groups. Treatment-emergent serious adverse events were similar across placebo and treatment groups. The most common reason for discontinuation was adverse events, predominantly gastrointestinal anddermatologic. Other adverse events occurring more frequentlyin patients undergoing treatment included reversibleglycosuria (without associated serum glucose changes), nonmelanoma skin cancer, and asymptomaticmagnetic resonance imaging findings. Exploratory cerebrospinal fluid amyloid isoforms and tau biomarker analysis demonstrated dose-dependent but not statistically significant reductions in a small subset of patients.

Conclusions: Avagacestat dosed at 25 and 50 mg daily was relatively well tolerated and had low discontinuation rates. The 100-mg and 125-mg dose arms were poorly tolerated with trends for cognitive worsening. Exploratory cerebrospinal fluid biomarker substudies provide preliminary support for -secretase target engagement,but additional studies are warranted to better characterize pharmacodynamic effects at the 25- and 50-mg doses.This study establishes an acceptable safety and tolerability dose range for future avagacestat studies in AD.

Trial registration: clinicaltrials.gov Identifier: NCT00810147

Background: Intracranial atherosclerosis is associated with recurrent ischemic stroke. High-resolution magnetic resonance imaging can provide information about atheroma in vivo including plaque volume, composition,and activity.

Objective: To evaluate atherosclerosis activity of the middle cerebral artery (MCA) by high-resolution magnetic resonance imaging and determine its relationship with infarction patterns.

Design: Patients with MCA territory infarction or transient ischemic attack were enrolled and 3-T high resolution magnetic resonance imaging was performed in the relevant MCA. We analyzed the status of the intracranial atheroma and infarction pattern in the corresponding vascular territory. Intracranial atheroma was defined as vulnerable symptomatic plaque when it was accompanied by intraplaque heterogeneous signal intensity and plaque enhancement, and as a stable symptomatic plaque otherwise. Cerebral infarction pattern was defined as artery-to-artery embolic infarction when multiple lesions were present within the MCA territory.

Setting: A tertiary referral center.

Patients: A total of 34 patients were enrolled in the study;14 patients had stable symptomatic plaque, 12 had vulnerable symptomatic plaque, and 8 had no plaque (normal group).

Main outcome measures: Intracranial atheroma stability and infarction pattern.

Results: High-resolution magnetic resonance images were acquired from 34 patients, which revealed the presence of stable symptomatic plaque in 14 patients and vulnerable symptomatic plaque in 12 patients. The patients with vulnerable symptomatic plaque more commonly demonstrated an artery-to-artery embolic infarction pattern than the patients with stable symptomatic plaque (P=.02).

Conclusions: Vulnerable symptomatic plaque as determined by a high-resolution magnetic resonance imaging technique is associated with artery-to-artery embolic infarction.This novel imaging technique can provide information about intracranial atherosclerosis in vivo, which can predict the infarction pattern.

Objective: To assess the hypothesis that use of anterior temporal lobectomy (ATL) for temporal epilepsy has diminished over time.

Design: Population-based cohort study.

Setting: The Rochester Epidemiology Project based in Olmsted County, Minnesota.

Participants: Residents of Olmsted County.

Main outcome measures: Poisson regression was used to evaluate changes in ATL use over time by sex.

Results: Over a 17-year period, from 1993 to 2009, 847ATLs were performed with the primary indication of epilepsy(average, 50 procedures/y). Of these, 26 occurred among Olmsted County residents. The use rates declinedsignificantly between 1993 and 2000 (8 years) and 2001 and 2009 (9 years) according to Poisson regression analysis, from 1.9 to 0.7 per 100 000 person-years(P=.01). The rate of ATL use among Olmsted County residents was 1.2 (95% CI, 0.9 to 2.4) per 100 000 person years of follow-up over this 17-year period. The sex specific rates were 1.6 (95% CI, 0.9 to 2.4) and 0.7 (95%CI, 0.2 to 1.3) per 100 000 person-years for females and males, respectively.

Conclusions: In this community-based cohort, the rate of ATL use was 1.2 per 100 000 person-years of followup.Use of this procedure has declined over time; the reasons for this are unknown but do not include referral pattern changes.