Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.
Campbell, B. C. V. et al. (2018) Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data. Lancet Neurology, 17(1), pp. 47-53. (doi:10.1016/S1474-4422(17)30407-6) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/149670/ variables. An alternative approach using propensity-score stratification was also used. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models. Bias was assessed using the Cochrane tool.Findings: Of 1764 patients in 7 trials, 871 were allocated to endovascular thrombectomy. After exclusion of 74 patients (72 who did not undergo the procedure and 2 with missing data on anaesthetic strategy), 236/797 (30%) of endovascular patients were treated under GA. At baseline, GA patients were younger and had shorter time to randomisation but similar pre-treatment clinical severity compared to non-GA. Endovascular thrombectomy improved functional outcome at 3 months versus standard care in both GA (adjusted common odds ratio (cOR) 1·52, 95%CI 1·09-2·11, p=0·014) and non-GA (adjusted cOR 2·33, 95%CI 1·75-3·10, p<0·001) patients. However, outcomes were significantly better for those treated under non-GA versus GA (covariate-adjusted cOR 1·53, 95%CI 1·14-2·04, p=0·004; propensitystratified cOR 1·44 95%CI 1·08-1·92, p=0·012). The risk of bias and variability among studies was assessed to be low.Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.
Funding:The HERMES collaboration was funded by an unrestricted grant from Medtronic to the University of Calgary.
Research in contextEvidence before this study between abolition of the thrombectomy treatment effect in MR CLEAN and no effect in THRACE. Three single-centre randomised trials of general anaesthesia versus conscious sedation found either no difference in functional outcome between groups or a slight benefit of general anaesthesia.
Added value of this studyThese data from contemporary, high quality randomised trials form the largest study to date of the association between general anesthesia and the benefit of endovascular thrombectomy versus standard care. We used two different approaches to adjust for baseline imbalances (multivariable logistic regression and propensity-score stratification). We found that GA for endovascular thrombectomy, as practiced in contemporary clinical care across a wide range of expert centres during the rand...
Frontotemporal dementia (FTD), characterized by behavioural and language disorders, is a clinically, genetically and pathologically heterogeneous group of diseases. The most recently identified of the four known genes is GRN, associated with 17q-linked FTD with ubiquitin-immunoreactive inclusions. GRN was analysed in 502 probands with frontal variant FTD (fvFTD), FTD with motoneuron disease (FTD-MND), primary progressive aphasia (PPA) and corticobasal degeneration syndrome (CBDS). We studied the clinical, neuropsychological and brain perfusion characteristics of mutation carriers. Eighteen mutations, seven novel were found in 24 families including 32 symptomatic mutation carriers. No copy number variation was found. The phenotypes associated with GRN mutations vary greatly: 20/32 (63%) carriers had fvFTD, the other (12/32, 37%) had clinical diagnoses of PPA, CBDS, Lewy body dementia or Alzheimer's disease. Parkinsonism developed in 13/32 (41%), visual hallucinations in 8/32 (25%) and motor apraxia in 5/21 (24%). Constructional disorders were present in 10/21 (48%). Episodic memory disorders were frequent (16/18, 89%), consistent with hippocampal amnestic syndrome in 5/18 (28%). Hypoperfusion was observed in the hippocampus, parietal lobe and posterior cingulate gyrus, as well as the frontotemporal cortices. The frequency of mutations according to phenotype was 5.7% (20/352) in fvFTD, 17.9% (19/106) in familial forms, 4.4% in PPA (3/68), 3.3% in CBDS (1/30). Hallucinations, apraxia and amnestic syndrome may help differentiate GRN mutation carriers from others FTD patients. Variable phenotypes and neuropsychological profiles, as well as brain perfusion profiles associated with GRN mutations may reflect different patterns of neurodegeneration. Since all the mutations cause a progranulin haploinsufficiency, additional factors probably explain the variable clinical presentation of the disease.
Cholinergic neurons were studied by immunohistochemistry, with an antiserum against choline acetyltransferase (ChAT), in the basal forebrain (Ch1 to Ch4) of four patients with Alzheimer's disease (AD) and four control subjects. ChAT-positive cell bodies were mapped and counted in Ch1 (medial septal nucleus), Ch2 (vertical nucleus of the diagonal band), Ch3 (horizontal nucleus of the diagonal band) and Ch4 (nucleus basalis of Meynert). Compared to controls, the number of cholinergic neurons in AD patients was reduced by 50% on average. The interindividual variations in cholinergic cell loss were high, neuronal loss ranging from moderate (27%) to severe (63%). Despite the small number of brains studied, a significant correlation was found between the cholinergic cell loss and the degree of intellectual impairment. To determine the selectivity of cholinergic neuronal loss in the basal forebrain of AD patients, NPY-immunoreactive neurons were also investigated. The number of NPY-positive cell bodies was the same in controls and AD patients. The results (1) confirm cholinergic neuron degeneration in the basal forebrain in AD and the relative sparing of these neurons in some patients, (2) indicate that degeneration of cholinergic neurons in the basal forebrain contributes to intellectual decline, and (3) show that, in AD, such cholinergic cell loss is selective, since NPY-positive neurons are preserved in the basal forebrain.
Aim: Determine whether patients with Alzheimer’s disease demonstrating functional and cognitive decline, following 24–48 weeks of open-label treatment with 9.5 mg/24 h (10 cm2) rivastigmine patch, benefit from a dose increase in a double-blind (DB) comparative trial of two patch doses. Methods: Patients meeting prespecified decline criteria were randomized to receive 9.5 or 13.3 mg/24 h (15 cm2) patch during a 48-week, DB phase. Coprimary outcomes were change from baseline to week 48 on the Instrumental Activities of Daily Living domain of the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-IADL) scale and the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog). Safety and tolerability were assessed. Results: Of 1,584 patients enrolled, 567 met decline criteria and were randomized. At all timepoints, ADCS-IADL and ADAS-cog scores favoured the 13.3 mg/24 h patch. The 13.3 mg/24 h patch was statistically superior to the 9.5 mg/24 h patch on the ADCS-IADL scale from week 16 (p = 0.025) onwards including week 48 (p = 0.002), and ADAS-cog at week 24 (p = 0.027), but not at week 48 (p = 0.227). No unexpected safety concerns were observed. Conclusions: The 13.3 mg/24 h rivastigmine patch significantly reduced deterioration in IADL, compared with the 9.5 mg/24 h patch, and was well tolerated.
Theory of Mind (ToM) is the ability to attribute independent mental states to self and others to explain and predict behavior. Impairment of ToM is well established in developmental pathologies. In neurological populations, investigation of ToM is still rare but data suggest that ToM impairment could contribute to behavioral and social disturbances. In addition to neurological signs, multiple sclerosis (MS) presents with disorders of cognition and behavior directly related to brain damage. The aim of this study was to assess ToM abilities and recognition of facial emotional expression in adults with MS. We compared 64 patients with relapsing MS and 30 matched healthy controls on three levels of ToM tasks, a facial emotion recognition task, and a neuropsychological assessment. MS patients performed significantly worse than controls in emotion recognition and all ToM tasks (p < .02). These deficits were not correlated with demographic variables or neuropsychological test performance. These findings underscore the importance of assessing ToM and facial recognition in MS, as dysfunction in these areas may impact upon social interaction and, thus, impair quality of life for both patients with MS and their families.
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