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Background It is likely that a proportion of poststroke cognitive impairment is sometimes attributable to unidentified prestroke decline; prestroke cognitive function is also clinically relevant because it is associated with poor functional outcomes, including death. We investigated the radiological and prognostic associations of preexisting cognitive impairment in patients with ischemic stroke or transient ischemic attack associated with atrial fibrillation. Methods and Results We included 1102 patients from the prospective multicenter observational CROMIS-2 (Clinical Relevance of Microbleeds in Stroke 2) atrial fibrillation study. Preexisting cognitive impairment was identified using the 16-item Informant Questionnaire for Cognitive Decline in the Elderly. Functional outcome was measured using the modified Rankin scale. Preexisting cognitive impairment was common (n=271; 24.6%). The presence of lacunes (odds ratio [OR], 1.50; 95% CI, 1.03-1.05; P =0.034), increasing periventricular white matter hyperintensity grade (per grade increase, OR, 1.38; 95% CI, 1.17-1.63; P <0.0001), deep white matter hyperintensity grade (per grade increase, OR, 1.26; 95% CI, 1.05-1.51; P =0.011), and medial temporal atrophy grade (per grade increase, OR, 1.61; 95% CI, 1.34-1.95; P <0.0001) were independently associated with preexisting cognitive impairment. Preexisting cognitive impairment was associated with poorer functional outcome at 24 months (mRS >2; adjusted OR, 2.43; 95% CI, 1.42-4.20; P =0.001). Conclusions Preexisting cognitive impairment in patients with atrial fibrillation-associated ischemic stroke or transient ischemic attack is common, and associated with imaging markers of cerebral small vessel disease and neurodegeneration, as well as with longer-term functional outcome. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02513316.

Objectives: CADASIL is a monogenic small vessel vasculopathy causing recurrent stroke. Early descriptions suggested dementia and disability were common from the 5th decade but there is evidence of marked phenotypic variability. We investigated the prevalence and clinical features of CADASIL in the west of Scotland., Methods: We undertook a retrospective review of clinical records of patients with confirmed CADASIL identified through a specialist clinic. Patients were divided to examine the effect of date of diagnosis on clinical outcomes and the characteristics at different ages. The location of pedigree members was used to estimate prevalence., Results: Twenty-one different CADASIL-causing NOTCH3 mutations were identified in 49 pedigrees (61% in exon 4). Disease prevalence in Glasgow was 4.6/100,000 adults. Mutation prevalence was estimated at 10.7/100,000 population. Median age at first stroke in women (57 years) was higher than previous estimates, and stroke age in men was higher in patients diagnosed more recently (pre 2006 46 years, post 2006 56 years, P=0.034). In patients over 58 years of age, 13/34 (38%) were living independently and 17/28 (61%) were mobile without aids when last seen., Conclusions: CADASIL prevalence is at least 4.6 per 100,000 adults. Median age of first stroke may be older than previously thought. Clinicians should consider CADASIL in the differential diagnosis even in older patients with stroke., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) has typical clinical features that include stroke, migraine, mood disturbances and cognitive decline. However, misdiagnosis is common. We hypothesized that family history is poorly elicited in individuals presenting with features of CADASIL and that enquiry into family history of all four cardinal manifestations of CADASIL is superior to elicitation of family history of premature stroke alone in raising the diagnostic possibility of CADASIL., Materials and Methods: Retrospective review of family histories at presentation in 40 individuals with confirmed CADASIL was performed through structured interview in a Neurovascular Genetics clinic (182 first-degree and 242 second-degree relatives identified). Family history obtained from structured interview was compared to family history initially documented at presentation., Results: At initial presentation, 30% of individuals were inaccurately documented to have no family history of significant neurological illness. Thirty-five per cent of patients had an initial alternative diagnosis. Initial inaccurate documentation of negative family history was more frequent in individuals with an initial alternative diagnosis. After structured interviews, 34% of 182 first-degree and 35% of 242 second-degree relatives of CADASIL patients had history of stroke (16% of first-degree relatives had stroke before the age of 50 years). Forty-three per cent of first-degree and 28% of second-degree relatives had migraine, mood disturbance or cognitive decline., Conclusions: A false-negative family history was commonly documented in individuals presenting with features of CADASIL and was associated with initial misdiagnosis. Restriction of family history to premature stroke alone is probably inadequate to identify affected CADASIL pedigrees.

The title complex, [Mo(C8F12)(C5H5)(C3H6NS2)], contains both a eta4-C4(CF3)4 cyclobutadienyl ligand with approximate C4v local symmetry and a eta5-C5H5 cyclopentadienyl ring. The centroids of the rings and the S atoms of a chelating dithiocarbamate ligand define the pseudo-tetrahedral coordination of the Mo atom. The Mo-C(cyclobutadienyl) bond lengths [2.189 (2)-2.211 (2) A] are unusually short, probably reflecting strong electron withdrawal by the trifluoromethyl groups. The molecules straddle crystallographic mirror planes.

In the title type B(2) acid salt, Na(LH)(LH(2)).H(2)O [LH(2) = C(2)H(4)C(CO(2)H)(2)] or Na(+).C(5)H(5)O(4)(-).C(5)H(6)O(4).H(2)O, the vertices of a distorted octahedron centred on each Na(+) cation are defined by six O atoms, one from a water molecule, one from an internally hydrogen-bonded LH(-) anion and four from three neutral LH(2) acid molecules. Chains of edge-sharing O(6) octahedra are stabilized by hydrogen bonds, which interconnect the donor H(2)O and LH(2) molecules and LH(-) anions. In particular, the LH(2) molecule donates H atoms to LH(-) and H(2)O and forgoes the internal hydrogen bond which stabilizes the free acid and all of its characterized salts.

In the title compound, hexa-micro-chloro-dichlorotetrakis(N-trimethylammonio-p-toluenesulfonamidate-kappa(2)N,O)tetramercury(II), [Hg[Me(3)N(+)N(-)SO(2)C(6)H(4)CH(3)-p]Cl(2)](4) or [Hg(4)Cl(8)(C(10)H(16)N(2)O(2)S)(4)], four nearly linear and parallel Cl-Hg-Cl units associate through pairwise Hg.Cl interactions of 3.1-3.2 A. Each Hg atom is also coordinated through N and O atoms to a ylide molecule. The available structural data indicate that coordination of a sulfonyl-stabilized nitrogen ylide to a metal atom (Hg or Ag) has no detectable effect on its geometry.

The structure of the cation in the ylide hydrochloride [Me(3)NNHC(O)C(6)H(4)-Cl-p]Cl.H(2)O, or C(10)H(14)ClN(2)O(+).Cl(-).H(2)O, is compared with that of the free ylide. Protonation lengthens the N-C(O) bond but shortens the C=O and N-N bonds by approximately 0.03 A and increases the dihedral angle between the phenyl and ylide planes.

The title disulfonyl-stabilized pyridinium ylide, C(5)H(5)N(+)-C(-)(SO(2)C(6)H(5))(2) or C(18)H(15)NO(4)S(2), contains a near planar NCS(2) core. The structure suggests that the formal negative charge of the ylide C atom is delocalized to the S atoms rather than the N atom. Structural features of pyridinium ylides are briefly discussed.

The racemic form of the title secondary monoalcohol, C(16)H(14)O, forms crystals in which the molecules are linked into chains by hydrogen bonding. The chain architecture is unusual; adjacent molecules are related pseudosymmetrically, by either a pseudo-diad or a pseudo-glide plane, while alternate molecules are related exactly by a crystallographic glide plane.

Objective: To determine the relationship between the apolipoprotein E (APOE) epsilon4 allele and in-hospital mortality from intracerebral haemorrhage (ICH)., Material and Methods: Patients admitted to two acute stroke units with ICH were prospectively evaluated and APOE genotyped. In-hospital survival was recorded in 176 patients., Results: There were 85 men and 91 women, mean age 68 years. Fifty-two (30%) of the 176 patients died in hospital. After adjusting for sex, age, hospital, and race, increased age (P = 0.009) and the presence of the APOEepsilon4 allele (P = 0.026) significantly reduced in-hospital survival., Conclusion: The APOEepsilon4 allele in this population may be associated with poor survival following ICH.

Crystals of 9-methylfluoren-9-ol, C(14)H(12)O, undergo a reversible phase transition at 176 (2) K. The structure of the high-temperature alpha form at 200 K is compared with that of the low-temperature beta form at 100 K. Both polymorphs crystallize in space group P1 with Z = 4 and contain discrete hydrogen-bonded R(4)(4)(8) ring tetramers arranged around crystallographic inversion centres. The most obvious changes observed on cooling the crystals to below 176 K are an abrupt increase of ca 0.5 A in the shortest lattice translation, and a thermal transition with deltaH = 1 kJ mol(-1).

The title compound, C23H23NO2SSi, at 100 K adopts a boat conformation which brings the C-H bond of an axial phenyl substituent into proximity [C...N = 3.376 (1) A] with the aziridine lone pair. The factors which favour this conformation for bicyclo[3.1.0]hexane systems are considered.

1. This was a multi-centre, placebo controlled, randomized, dose-escalating design study in which five dosing regimens of 619C89/placebo were evaluated in 48 stroke patients. Loading infusions of 0.5, 1, 1.5, 2 and 2.5 mg kg-1 over 1 h were followed by respective maintenance infusions of 0.25, 0.5, 0.75, 1 and 1.25 mg kg-1 over 30 min at 8 hourly intervals for 3 days. 2. Plasma concentrations of 619C89 and its N-oxide, 341C90, and N-demethylated, 78C90, metabolites were assayed using an LC-MS-MS method. Plasma concentration-time profiles after the final maintenance infusion were subjected to conventional noncompartmental pharmacokinetic analysis. 3. For 619C89, geometric CL means ranged between 0.71 and 0.99 1 h-1 kg-1 for maintenance infusions up to 1.25 mg kg-1 over 30 min, with an overall mean of 0.85 l h-1 kg-1 (95% CI: 0.70-1.04 l h-1 kg-1). Geometric Vss means ranged between 13.2 and 27.9 l kg-1 for the same doses, with an overall mean of 22.5 l kg-1 (95% CI: 16.4-30.9 l kg-1). The ANOVA results revealed that neither CL, Vss nor t1/2 were significantly different across the five dosing regimens (P values: 0.82, 0.54 and 0.61, respectively). 4. Average AUC for 341C90 was 270% and that for 78C90 was 62% of the AUC for 619C89. The AUCm/AUCp-ratios were similar at all dose levels for each metabolite. Values of t 1/2 for 341C90 were similar to those of 619C89 whereas t1/2 for 78C90 was about three-fold longer than that of parent drug. 5. In conclusion, the pharmacokinetics of 619C89 are independent of dose in acute stroke patients. The pharmacokinetics of 341C90 are probably formation rate-limited and those of 78C90 are elimination rate-limited and are also dose-independent.

1. Non-competitive antagonists at the glutamatergic N-methyl D-aspartate receptor significantly reduce the volume of ischaemic cerebral infarction in animals and are potential agents for the treatment of acute stroke in humans. 2. CNS 1102, a novel non-competitive NMDA antagonist, was administered as a 15 min intravenous infusion to healthy male volunteers in a double-blind, placebo-controlled, dose-ranging study. This was the first administration to man. 3. Clinically significant sedation, increased mean arterial pressure and pulse rate were seen at doses of 30 micrograms kg-1 and above. Symptoms of sedation and central nervous excitation became unacceptable for conscious individuals at doses of 45 micrograms kg-1 and above. 4. Rapid onset of central nervous system effects after administration is in keeping with rapid distribution of CNS 1102 to brain. Steady state volume of distribution was large (444 l) and terminal elimination half-life from plasma was approximately 4 h. 5. Pharmacokinetic properties are favourable for a potential neuroprotective therapy. The maximum tolerated dose for conscious individuals was 30 micrograms kg-1 given intravenously over 15 min. Further assessment of CNS 1102 should seek methods of drug administration which maximise administered dose with minimal side effects.