Does genetic anticipation occur in familial Alexander disease?

Alexander Disease (AxD) is a rare leukodystrophy caused by missense mutations of glial fibrillary acidic protein (GFAP). Primarily seen in infants and juveniles, it can present in adulthood. We report a family with inherited AxD in which the mother presented with symptoms many years after her daughter. We reviewed the age of onset in all published cases of familial AxD and found that 32 of 34 instances of parent-offspring pairs demonstrated an earlier age of onset in offspring compared to the parent. We suggest that genetic anticipation occurs in familial AxD and speculate that genetic mosaicism could explain this phenomenon.

Long-term outcome after angioplasty and stenting for symptomatic vertebral artery stenosis compared with medical treatment in the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomized trial.

BACKGROUND AND PURPOSE: The long-term outcome of endovascular intervention compared with best medical management of patients with symptomatic vertebral artery stenosis is uncertain. We therefore compared these treatments in a randomized trial with long-term follow-up. METHODS: In the international, multicenter Carotid And Vertebral Artery Transluminal Angioplasty Study, 16 patients with symptomatic vertebral artery stenosis were randomized in equal proportions to receive endovascular therapy (balloon angioplasty or stenting) or best medical treatment alone. An independent neurologist followed up the patients for as long as 8 years. RESULTS: Endovascular intervention was technically successful in all 8 patients, but 2 patients experienced transient ischemic attack at the time of endovascular treatment. There were no deaths or strokes in any arterial territory within the first 30 days. During a mean follow-up period of 4.7 years, no patient in either treatment group experienced a vertebrobasilar territory stroke, but 3 patients in each treatment arm died of myocardial infarction or carotid territory stroke, and 1 endovascular patient had a nonfatal carotid territory stroke. CONCLUSIONS: Patients with vertebral artery stenosis were more likely to have carotid territory stroke and myocardial infarction during follow-up than have recurrent vertebrobasilar stroke. The trial failed to show a benefit of endovascular treatment of vertebral artery stenosis, but the numbers of patients included was small. Larger randomized trials are required to determine whether vertebral artery stenting is justified in patients at higher risk of vertebrobasilar stroke. Treatment of patients with vertebral artery stenosis should focus on global reduction of vascular risk, including prevention of carotid territory stroke and myocardial infarction.

Simple models improve the discrimination of prostate cancers from the peripheral gland by T1-weighted dynamic MRI.

Evaluation of the accuracy of descriptive and physiological parameters calculated from signal intensity-time curves using T1-weighted dynamic contrast enhanced MRI (DCE MRI) to differentiate prostate cancers from the peripheral gland. Twenty-seven patients with prostate cancers were examined with DCE MRI prior radical prostatectomy. Regions of interest were defined in tumors and non-affected areas in the peripheral zone. Dynamic data were parameterized in amplitude and exchange rate constant (kep) using a two-compartment model. Additionally, relative slope during 26, 39, 52 and 65 s, areas under the curve (AUC) and time to start of signal intensity increase (tlag) were determined. Vessel density (VD) of excised prostates was quantified in tumor areas using a CD34 stain. The parameter slope52 showed 20% higher values (P<0.001) in tumors than in the peripheral gland and compared with the other parameters the largest area under the ROC curve (0.81). The minimum total error rate was attained at a cut-point of 0.021, yielding a sample value of sensitivity and specificity of 70% and 88%, respectively, and a bias-corrected sum of sensitivity and specificity of 1.54. In addition, amplitude (P<0.001), kep (P=0.03) and AUC (P<0.001) were significantly higher in tumors. tlag did not discriminate carcinomas from glandular tissue. VD was higher in tumors than in the non-affected peripheral prostate (P=0.05). However, none of the dynamic parameters in carcinomas showed a significant correlation with VD or Gleason score. Although pharmacokinetic modeling in DCE MRI showed potential to discriminate prostate cancers from peripheral prostate tissue, descriptive parameters of the early signal enhancement after contrast media injection reached higher sensitivity and specificity.