Brain microbleeds on gradient-recalled echo (GRE) T2*-weighted MRI may be a useful biomarker for bleeding-prone small vessel diseases, with potential relevance for diagnosis, prognosis (especially ...for antithrombotic-related bleeding risk), and understanding mechanisms of symptoms, including cognitive impairment. To address these questions, it is necessary to reliably measure their presence and distribution in the brain. We designed and systematically validated the Microbleed Anatomical Rating Scale (MARS). We measured intrarater and interrater agreement for presence, number, and anatomical distribution of microbleeds using MARS across different MRI sequences and levels of observer experience.
We studied a population of 301 unselected consecutive patients admitted to our stroke unit using 2 GRE T2*-weighted MRI sequences (echo time TE 40 and 26 ms). Two independent raters with different MRI rating expertise identified, counted, and anatomically categorized microbleeds.
At TE = 40 ms, agreement for microbleed presence in any brain location was good to very good (intrarater kappa = 0.85 95% confidence interval (CI) 0.77-0.93; interrater kappa = 0.68 95% CI 0.58-0.78). Good to very good agreement was reached for the presence of microbleeds in each anatomical region and in individual cerebral lobes. Intrarater and interrater reliability for the number of microbleeds was excellent (intraclass correlation coefficient ICC = 0.98 95% CI 0.97-0.99 and ICC = 0.93 0.91-0.94). Very good interrater reliability was obtained at TE = 26 ms (kappa = 0.87 95% CI 0.61-1) for definite microbleeds in any location.
The Microbleed Anatomical Rating Scale has good intrarater and interrater reliability for the presence of definite microbleeds in all brain locations when applied to different MRI sequences and levels of observer experience.
MRI-visible perivascular spaces (PVS) are potential neuroimaging markers of cerebral small vessel disease, but their functional significance and mechanisms remain uncertain. We investigated the ...association between PVS and cognitive impairment, and other MRI markers of small vessel disease, in a patient cohort of ischaemic stroke/transient ischaemic attack (TIA) referrals.
Data were collected from a prospective observational database. Standardised detailed neuropsychological testing was performed. A validated visual rating scale on T2-weighted MRI was used to categorise PVS severity; validated scales were used to assess white matter hyperintensities (WMH), cerebral microbleeds (CMB) and lacunes.
We included 246 patients (45.1% female, mean age 62 years). No significant association between PVS severity grade in any brain region and impairment in any cognitive domain was identified. In multivariable analysis, WMH and hypertension (but not age) were independently associated with basal ganglia PVS severity (OR: 1.27; p<0.0001 and OR: 4.89; p=0.013, respectively). Increasing PVS severity in the basal ganglia was associated with lacunar stroke subtype (p<0.0001). Age and hypertension (but not WMH or lacunar stroke subtype) were independently associated with centrum semiovale PVS severity (OR: 1.19; p=0.013 and OR: 3.71; p=0.007, respectively).
PVS do not have an independent association with cognitive impairment in patients with ischaemic stroke or TIA. The associations with clinical-radiological factors are consistent with the hypothesis that PVS reflect cerebral small vessel disease; the different associations for basal ganglia and centrum semiovale PVS might indicate different underlying small vessel arteriopathies according to PVS anatomical distribution, but this requires further study.
Objective
To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants Vitamin K ...antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH) and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.
Methods
We conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel–Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.
Results
We identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03–7.07,
p
< 0.0001,
I
2
= 92%,
p
< 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24–13.07 ml,
p
< 0.00001;
I
2
= 42%,
p
= 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74–4.97,
p
< 0.00001;
I
2
= 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61–2.07,
p
< 0.00001,
I
2
= 20%,
p
= 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52–3.31,
p
< 0.00001,
I
2
= 71%,
p
= 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.
Conclusion
This meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.
Diffusion tensor imaging (DTI) fully characterises water molecule mobility in vivo, allowing an exploration of fibre tract integrity and orientation in the human brain. Using DTI this study ...demonstrates reduced fibre coherence (anisotropy) associated with cerebral infarction and in the corticospinal tract remote from the lesion, in five patients 2 to 6 months after ischaemic stroke. The study highlights the potential of DTI to detect and monitor the structural degeneration of fibre pathways, which may provide a better understanding of the pattern of clinical evolution after stroke.
Background
Established features of classical infratentorial superficial siderosis (iSS) include hearing loss, impaired balance, myelopathy and, less commonly, cognitive compromise. Olfactory function ...may be affected but dedicated studies are lacking. This study aimed to assess the prevalence of olfactory dysfunction in iSS and correlate it with auditory and cognitive functions.
Methods
Ten participants with iSS completed the University of Pennsylvania Smell Identification Test (UPSIT). The scores were compared with population norms; regression analysis was performed to evaluate associations between the scores and hearing thresholds (3-frequency average, 3FA) or the number of cognitive domains impaired. Imaging was reviewed for haemosiderin distribution and to exclude other causes of olfactory and hearing dysfunction.
Results
Eight of ten participants were male; the mean (standard deviation, SD) age was 52.5 (14.5) years. Olfactory hypofunction was identified in all participants and in six (60%) was moderate or completely absent. The mean UPSIT score of 25.5 (7.8) was significantly worse than population norms (difference in means − 10.0; 95% CI − 15.6 to − 4.4). Linear regression identified an association between UPSIT and hearing thresholds (
R
= 0.75;
p
= 0.013). The score decreases by 0.157 units (95% CI − 0.31 to − 0.002;
p
= 0.048) per unit increase in 3FA, after adjusting for hearing loss risk factors. There was no statistically significant association between UPSIT and cognitive function (
R
= 0.383;
p
= 0.397).
Conclusion
We report a high prevalence of olfactory dysfunction in iSS, the severity of which correlated with hearing loss. Olfaction appears to be a core feature of the iSS clinical syndrome that should be assessed routinely.
Background and purpose
There are very few studies of the characteristics and causes of ICH in COVID-19, yet such data are essential to guide clinicians in clinical management, including challenging ...anticoagulation decisions. We aimed to describe the characteristics of spontaneous symptomatic intracerebral haemorrhage (ICH) associated with COVID-19.
Methods
We systematically searched PubMed, Embase and the Cochrane Central Database for data from patients with SARS-CoV-2 detected prior to or within 7 days after symptomatic ICH. We did a pooled analysis of individual patient data, then combined data from this pooled analysis with aggregate-level data.
Results
We included data from 139 patients (98 with individual data and 41 with aggregate-level data). In our pooled individual data analysis, the median age (IQR) was 60 (53–67) years and 64% (95% CI 54–73.7%) were male; 79% (95% CI 70.0–86.9%) had critically severe COVID-19. The pooled prevalence of lobar ICH was 67% (95% CI 56.3–76.0%), and of multifocal ICH was 36% (95% CI 26.4–47.0%). 71% (95% CI 61.0–80.4%) of patients were treated with anticoagulation (58% (95% CI 48–67.8%) therapeutic). The median NIHSS was 28 (IQR 15–28); mortality was 54% (95% CI 43.7–64.2%). Our combined analysis of individual and aggregate data showed similar findings. The pooled incidence of ICH across 12 cohort studies of inpatients with COVID-19 (
n
= 63,390) was 0.38% (95% CI 0.22–0.58%).
Conclusions
Our data suggest that ICH associated with COVID-19 has different characteristics compared to ICH not associated with COVID-19, including frequent lobar location and multifocality, a high rate of anticoagulation, and high mortality. These observations suggest different underlying mechanisms of ICH in COVID-19 with potential implications for clinical treatment and trials.
To determine whether diffusion tensor imaging (DTI) can detect structural changes in normal-appearing white matter, and to distinguish between plaques of different pathologic severity, in patients ...with MS.
Conventional MRI detects lesions sensitively in MS but has limited pathologic specificity. The diffusion of water molecules in brain tissue, most fully expressed mathematically by a tensor quantity, reflects its intrinsic microstructure. It is now possible to estimate the diffusion tensor noninvasively in the human brain using MR DTI. This method is unique in providing precise and rotationally invariant measurements of the amount and directional bias (anisotropy) of diffusion in white matter tracts relating to tissue integrity and orientation.
DTI was performed in six patients with MS and in six age-matched control subjects. Diffusion was characterized in normal-appearing white matter in both groups, and in lesions of different pathologic subtypes (inflammatory, noninflammatory, T1 hypointense, and T1 isointense).
DTI identified significantly altered water diffusion properties in the normal-appearing white matter of patients compared with control subjects (p < 0.001), and distinguished between lesion types. The highest diffusion was seen in destructive (T1 hypointense) lesions, whereas the greatest change in anisotropy was found in inflammatory (gadolinium-enhancing) lesions.
DTI detects diffuse abnormalities in the normal-appearing white matter of MS patients, and the findings in lesions appear to relate to pathologic severity. Its use in serial studies and in larger clinical cohorts may increase our understanding of pathogenetic mechanisms of reversible and persistent disability.
Intracerebral haemorrhage (ICH) is an uncommon but devastating complication of regular antiplatelet use: identifying high-risk patients before treatment could potentially reduce this hazard. Brain ...microbleeds on gradient-recalled echo (GRE) T2*-weighted MRI are considered a biomarker for bleeding-prone small-vessel diseases. The authors hypothesised that microbleeds are a risk factor for antiplatelet-related ICH, and investigated this in a hospital-based matched case-control study.
Cases of spontaneous ICH were ascertained, using overlapping methods, from a prospective database of 1017 consecutive unselected patients referred to our stroke unit and associated clinics. For each case of antiplatelet-related ICH, two controls matched for age, sex and hypertension without history of ICH on antiplatelet therapy were selected. Microbleeds were identified by a trained observer blinded to clinical details.
Microbleeds were more frequent in antiplatelet users with ICH than in matched antiplatelet users without ICH (13/16 (81%) vs 6/32 (19%), p=0.004) and patients with non-antiplatelet-related ICH (13/16 (81%) vs 15/33 (45%), p=0.03). The frequency of lobar microbleeds was 11/16 (69%) in antiplatelet-related ICH versus 11/33 (33%) in non antiplatelet-related ICH (p=0.032). Microbleeds were more numerous in antiplatelet users with ICH compared with controls (p=0.016). The number of microbleeds was associated with the risk of antiplatelet-related ICH (adjusted OR 1.33 per additional microbleed, 95% CI 1.06 to 1.66, p=0.013).
Brain microbleeds are associated with antiplatelet-related ICH. In patients with a large number of lobar microbleeds, the risk of ICH could outweigh the benefits of antiplatelet therapy. Larger prospective studies to investigate the prognostic significance of microbleeds in regular antiplatelet users are warranted.
Suspected transient ischaemic attack (TIA) is a common diagnostic challenge for physicians in neurology, stroke, general medicine and primary care. It is essential to identify TIAs promptly because ...of the very high early risk of ischaemic stroke, requiring urgent investigation and preventive treatment. On the other hand, it is also important to identify TIA 'mimics', to avoid unnecessary and expensive investigations, incorrect diagnostic labelling and inappropriate long-term prevention treatment. Although the pathophysiology of ischaemic stroke and TIA is identical, and both require rapid and accurate diagnosis, the differential diagnosis differs for TIA owing to the transience of symptoms. For TIA the diagnostic challenge is greater, and the 'mimic' rate higher (and more varied), because there is no definitive diagnostic test. TIA heralds a high risk of early ischaemic stroke, and in many cases the stroke can be prevented if the cause is identified, hence the widespread dissemination of guidelines including rapid assessment and risk tools like the ABCD2 score. However, these guidelines do not emphasise the substantial challenges in making the correct diagnosis in patients with transient neurological symptoms. In this article we will mainly consider the common TIA mimics, but also briefly mention the rather less common situations where TIAs can look like something else ('chameleons').
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