Long-term mortality, disability and stroke recurrence in patients with basilar artery occlusion.

BACKGROUND AND PURPOSE: The long-term outcomes and stroke recurrence after basilar artery occlusion (BAO) are largely unknown. We aimed to assess these variables in a comparatively large series of consecutive patients. METHODS: Adults with acute BAO were retrospectively identified from 1976 to 2011. Post-discharge records were reviewed to assess for stroke recurrences, mortality and disability. Exploratory analysis of survival was carried out using Kaplan-Meier and log-rank tests. Factors associated with survival time were determined using Cox models. RESULTS: A total of 86 patients (34% female, median age 72 [interquartile range (IQR), 60-79] years) with a median National Institutes of Health Stroke Scale score of 11 (IQR, 6-27) were included. Twenty-nine patients (34%) died during the initial hospitalization. Median modified Rankin Scale (mRS) score at discharge among survivors was 4 (IQR, 2.5-5.5). At 1 and 5 years, 70% of survivors ad a mRS ≤3. Seventeen patients had recurrent strokes during the hospitalization and 12 patients had 19 recurrent strokes after discharge. The median survival time was 52 days (IQR, 6-1846). Older age per decade on admission [adjusted hazard ratios (aHR), 1.32; 95% confidence interval (CI), 1.05-1.66, P = 0.02] and a higher mRS at discharge (aHR, 4.48; 95% CI, 2.72-7.39, P < 0.0001) were associated with mortality. Patients who were not treated with any reperfusion therapy had a trend towards reduced mortality (aHR, 0.39; 95% CI, 0.14-1.08, P = 0.07). CONCLUSIONS: Survivors from BAO had severe short-term functional disability. Most deaths and stroke recurrences occurred within the first year following the initial event. The risk of death was higher in older and more disabled survivors. However, favorable long-term recovery was possible.

Similar clinical and neuroimaging features in monozygotic twin pair with mutation in progranulin.

OBJECTIVE: To report the phenotypic characterization of monozygotic twins with mutations encoding progranulin (PGRN). METHODS: We studied a twin pair with an exon 4 gene deletion in the PGRN gene. Both twins had clinical and neuropsychological examinations as well as structural MRI and fluorodeoxyglucose PET (FDG-PET) scans. PGRN gene sequencing was performed followed by progranulin ELISA in plasma. RESULTS: Both twins manifested symptoms within 3 years of each other, with early behavioral, language, dysexecutive, and memory problems. MRI and FDG-PET imaging demonstrated a strikingly similar topography of findings with clear left hemisphere predominance. Serum progranulin levels in both were well below those from a normal population sample. CONCLUSIONS: Compared with the heterogeneity seen in many families with PGRN mutations, these monozygotic twins demonstrated strong clinical, neuroimaging, and serum progranulin level similarities, demonstrating the importance of shared genetic profiles beyond environmental influences in the symptomatic expression of the disease.

Pyrimido[1,2-alpha]purin-10(3H)-one: a reactive electrophile in the genome.

Malondialdehyde and base propenal react with deoxyguanosine residues in DNA to form an exocyclic adduct, pyrimido[1, 2-alpha]purin-10(3H)-one (1), that has been detected at high levels in genomic DNA of healthy humans. Previous studies have shown that tris(hydroxymethyl)aminomethane adds to 1 at elevated pH, forming an enaminoimine (2), but it is uncertain whether 1 reacts directly or hydrolyzes under basic conditions to N(2)-(3-oxo-1-propenyl)deoxyguanosine (3) prior to amine addition. We report that 1 reacts at neutral pH with hydroxylamines to form oximes. The rate of reaction of 1 with hydroxylamines at pH 7 is at least 150 times faster than the rate of hydrolysis of 1 to 3. Thus, 1 is directly reactive to nucleophiles. These observations indicate that 1 is an electrophile in the human genome that may react with cellular nucleophiles to form novel cross-linked adducts.