Patrice Laloux

Spectrum of transient focal neurological episodes in cerebral amyloid angiopathy: multicentre magnetic resonance imaging cohort study and meta-analysis.

Background and Purpose— Transient focal neurological episodes (TFNE) are recognized in cerebral amyloid angiopathy (CAA) and may herald a high risk of intracerebral hemorrhage (ICH). We aimed to determine their prevalence, clinical neuroimaging spectrum, and future ICH risk. Methods— This was a multicenter retrospective cohort study of 172 CAA patients. Clinical, imaging, and follow-up data were collected. We classified TFNE into: predominantly positive symptoms (“aura-like” spreading paraesthesias/positive visual phenomena or limb jerking) and predominantly negative symptoms (“transient ischemic attack–like” sudden-onset limb weakness, dysphasia, or visual loss). We pooled our results with all published cases identified in a systematic review. Results— In our multicenter cohort, 25 patients (14.5%; 95% confidence interval, 9.6%–20.7%) had TFNE. Positive and negative symptoms were equally common (52% vs 48%, respectively). The commonest neuroimaging features were leukoaraiosis (84%), lobar ICH (76%), multiple lobar cerebral microbleeds (58%), and superficial cortical siderosis/convexity subarachnoid hemorrhage (54%). The CAA patients with TFNE more often had superficial cortical siderosis/convexity subarachnoid hemorrhage (but not other magnetic resonance imaging features) compared with those without TFNE (50% vs 19%; P=0.001). Over a median period of 14 months, 50% of TFNE patients had symptomatic lobar ICH. The meta-analysis showed a risk of symptomatic ICH after TFNE of 24.5% (95% confidence interval, 15.8%–36.9%) at 8 weeks, related neither to clinical features nor to previous symptomatic ICH. Conclusions— TFNE are common in CAA, include both positive and negative neurological symptoms, and may be caused by superficial cortical siderosis/convexity subarachnoid hemorrhage. TFNE predict a high early risk of symptomatic ICH (which may be amenable to prevention). Blood-sensitive magnetic resonance imaging sequences are important in the investigation of such episodes.

Acute ischaemic brain lesions in intracerebral haemorrhage : multicentre cross-sectional magnetic resonance imaging study.

Subclinical acute ischaemic lesions on brain magnetic resonance imaging have recently been described in spontaneous intracerebral haemorrhage, and may be important to understand pathophysiology and guide treatment. The underlying mechanisms are uncertain. We tested the hypothesis that ischaemic lesions are related to magnetic resonance imaging markers of the severity and type of small-vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy) in a multicentre, cross-sectional study. We studied consecutive patients with intracerebral haemorrhage from four specialist stroke centres, and age-matched stroke service referrals without intracerebral haemorrhage. Acute ischaemic lesions were assessed on magnetic resonance imaging (<3 months after intracerebral haemorrhage) using diffusion-weighted imaging. White matter changes and cerebral microbleeds were rated with validated scales. We investigated associations between diffusion-weighted imaging lesions, clinical and radiological characteristics. We included 114 patients with intracerebral haemorrhage (39 with clinically probable cerebral amyloid angiopathy) and 47 age-matched controls. The prevalence of diffusion-weighted imaging lesions was 9/39 (23%) in probable cerebral amyloid angiopathy-related intracerebral haemorrhage versus 6/75 (8%) in the remaining patients with intracerebral haemorrhage (P = 0.024); no diffusion-weighted imaging lesions were found in controls. Diffusion-weighted imaging lesions were mainly cortical and were associated with mean white matter change score (odds ratio 1.14 per unit increase, 95% confidence interval 1.02-1.28, P = 0.024) and the presence of strictly lobar cerebral microbleeds (odds ratio 3.85, 95% confidence interval 1.15-12.93, P = 0.029). Acute, subclinical ischaemic brain lesions are frequent but previously underestimated after intracerebral haemorrhage, and are three times more common in cerebral amyloid angiopathy-related intracerebral haemorrhage than in other intracerebral haemorrhage types. Ischaemic brain lesions are associated with white matter changes and cerebral microbleeds, suggesting that they result from an occlusive small-vessel arteriopathy. Diffusion-weighted imaging lesions contribute to the overall burden of vascular-related brain damage in intracerebral haemorrhage, and may be a useful surrogate marker of ongoing ischaemic injury from small-vessel damage.

Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy.

Objective: To investigate whether cortical superficial siderosis (cSS) on MRI, especially if disseminated (involving more than 3 sulci), increases the risk of future symptomatic lobar intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA). Methods: European multicenter cohort study of 118 patients with CAA (104 with baseline symptomatic lobar ICH) diagnosed according to the Boston criteria. We obtained baseline clinical, MRI, and follow-up data on symptomatic lobar ICH. Using Kaplan-Meier and Cox regression analyses, we investigated cSS and ICH risk, adjusting for known confounders. Results: During a median follow-up time of 24 months (interquartile range 9–44 months), 23 of 118 patients (19.5%, 95% confidence interval [CI]: 12.8%–27.8%) experienced symptomatic lobar ICH. Any cSS and disseminated cSS were predictors of time until first or recurrent ICH (log-rank test: p = 0.0045 and p = 0.0009, respectively). ICH risk at 4 years was 25% (95% CI: 7.6%–28.3%) for patients without siderosis; 28.9% (95% CI: 7.7%–76.7%) for patients with focal siderosis; and 74% (95% CI: 44.1%–95.7%) for patients with disseminated cSS (log-rank test: p = 0.0031). In Cox regression models, any cSS and disseminated cSS were both independently associated with increased lobar ICH risk, after adjusting for ≥2 microbleeds and age (hazard ratio: 2.53; 95% CI: 1.05–6.15; p = 0.040 and hazard ratio: 3.16; 95% CI: 1.35–7.43; p = 0.008, respectively). These results remained consistent in sensitivity analyses including only patients with symptomatic lobar ICH at baseline. Conclusions: Our findings indicate that cSS, particularly if disseminated, is associated with an increased risk of symptomatic lobar ICH in CAA. cSS may help stratify future bleeding risk in CAA, with implications for prognosis and treatment.

Dual-tDCS Enhances Online Motor Skill Learning and Long-Term Retention in Chronic Stroke Patients.

Background: Since motor learning is a key component for stroke recovery, enhancing motor skill learning is a crucial challenge for neurorehabilitation. Transcranial direct current stimulation (tDCS) is a promising approach for improving motor learning. The aim of this trial was to test the hypothesis that dual-tDCS applied bilaterally over the primary motor cortices (M1) improves online motor skill learning with the paretic hand and its long-term retention. Methods: Eighteen chronic stroke patients participated in a randomized, cross-over, placebo-controlled, double bind trial. During separate sessions, dual-tDCS or sham dual-tDCS was applied over 30 min while stroke patients learned a complex visuomotor skill with the paretic hand: using a computer mouse to move a pointer along a complex circuit as quickly and accurately as possible. A learning index involving the evolution of the speed/accuracy trade-off was calculated. Performance of the motor skill was measured at baseline, after intervention and 1 week later. Results: After sham dual-tDCS, eight patients showed performance worsening. In contrast, dual-tDCS enhanced the amount and speed of online motor skill learning compared to sham (p < 0.001) in all patients; this superiority was maintained throughout the hour following. The speed/accuracy trade-off was shifted more consistently after dual-tDCS (n = 10) than after sham (n = 3). More importantly, 1 week later, online enhancement under dual-tDCS had translated into superior long-term retention (+44%) compared to sham (+4%). The improvement generalized to a new untrained circuit and to digital dexterity. Conclusion: A single-session of dual-tDCS, applied while stroke patients trained with the paretic hand significantly enhanced online motor skill learning both quantitatively and qualitatively, leading to successful long-term retention and generalization. The combination of motor skill learning and dual-tDCS is promising for improving post-stroke neurorehabilitation.

Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy

Objective: We investigated the prevalence and clinical-radiologic associations of cortical superficial siderosis (cSS) in patients with probable cerebral amyloid angiopathy (CAA) compared to those with intracerebral hemorrhage (ICH) not attributed to CAA. Methods: We conducted a retrospective multicenter cohort study of 120 patients with probable CAA and 2 comparison groups: 67 patients with either single lobar ICH or mixed (deep and lobar) hemorrhages; and 22 patients with strictly deep hemorrhages. We rated cSS, ICH, white matter changes, and cerebral microbleeds. Results: cSS was detected in 48 of 120 (40%; 95% confidence interval [CI]: 31.2%–49.3%) patients with probable CAA, 10 of 67 (14.9%; 95% CI: 7.4%–25.7%) with single lobar ICH or mixed hemorrhages, and 1 of 22 (4.6%; 95% CI: 0.1%–22.8%) patients with strictly deep hemorrhages (p < 0.001 for trend). Disseminated cSS was present in 29 of 120 (24%; 95% CI: 16.8%–32.8%) patients with probable CAA, but none of the other patients with ICH (p < 0.001). In probable CAA, age (odds ratio [OR]: 1.09; 95% CI: 1.03–1.15; p = 0.002), chronic lobar ICH (OR: 3.94; 95% CI: 1.54–10.08; p = 0.004), and a history of transient focal neurologic episodes (OR: 11.08; 95% CI: 3.49–35.19; p < 0.001) were independently associated with cSS. However, cSS occurred in 17 of 48 patients with probable CAA (35.4%; 95% CI: 22.2%–50.5%) without chronic lobar ICH. Conclusions: cSS (particularly if disseminated) is a common and characteristic feature of CAA. Chronic lobar ICH is an independent risk factor for cSS, but the causal direction and mechanism of association are uncertain. Hemorrhage into the subarachnoid space, independent of previous (chronic) lobar ICH, must also contribute to cSS in CAA. Transient focal neurologic episodes are the strongest clinical marker of cSS.

Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study

Background and purpose Small vessel disease (mainly hypertensive arteriopathy and cerebral amyloid angiopathy (CAA)) is an important cause of spontaneous intracerebral haemorrhage (ICH), a devastating and still poorly understood stroke type. Enlarged perivascular spaces (EPVS) are a promising neuroimaging marker of small vessel disease. Based on the underlying arteriopathy distributions, we hypothesised that severe centrum semiovale EPVS are more common in lobar ICH attributed to CAA than other ICH. We evaluated EPVS prevalence, severity and distribution, and their clinical–radiological associations. Methods Retrospective multicentre cohort study of 121 ICH patients. Clinical information was obtained using standardised forms. Basal ganglia and centrum semiovale EPVS on T2-weighted MRI (graded 0–4 (>40 EPVS)), white-matter changes, cerebral microbleeds (CMBs) and lacunes were rated using validated scales. Results Patients with probable or possible CAA (n=76) had a higher prevalence of severe (>40) centrum semiovale EPVS compared with other ICH patients (35.5% vs 17.8%; p=0.041). In logistic regression age (OR: 1.43; 95% CI 1.01 to 2.02; p=0.045), deep CMBs (OR: 3.27; 95% CI 1.27 to 8.45; p=0.014) and mean white-matter changes score (OR: 1.29; 95% CI 1.17 to 1.43; p<0.0001) were independently associated with increased basal ganglia EPVS severity; only age was associated with increased centrum semiovale EPVS severity (OR: 1.50; 95% CI 1.08 to 2.10; p=0.017). Conclusions EPVS are common in ICH. Different mechanisms may account for EPVS according to their anatomical distribution. Severe centrum semiovale EPVS may be secondary to, and indicative of, CAA with value as a new neuroimaging marker. By contrast, basal ganglia EPVS severity is associated with markers of hypertensive arteriopathy.

Comparative correlations of HMPAO SPECT indices, neurological score, and stroke subtypes with clinical outcome in acute carotid infarcts.

BACKGROUND AND PURPOSE The prognostic value of single-photon emission computed tomography (SPECT) remains controversial. The aim of this study was to compare the prognostic value of stroke severity, stroke subtypes, and SPECT indices and to determine which predictive factors have an independent effect on clinical outcome. METHODS We studied 55 consecutive patients with acute (< 12 hours) carotid infarct within 36 hours of symptom onset with SPECT. Clinical presentation was assessed by the Canadian Neurological Scale and stroke subtypes. SPECT indices were the degree and size of hypoperfusion and crossed cerebellar diaschisis as assessed by a semiquantitative analysis. Outcome was evaluated by the functional status and mortality (Rankin Scale score at 1 month). RESULTS The Rankin Scale score correlated with the degree (r = .580; P < .00001) and size (r = .616; P < .00001) of hypoperfusion. The mean degree and size of hypoperfusion were significantly higher in patients with poor outcome. Crossed cerebellar diaschisis had no significant predictive value. Statistical analysis determined threshold values for the Canadian Neurological Scale score and the degree and size of hypoperfusion for the functional status and mortality. The degree and size of hypoperfusion had no higher performance than the Canadian Neurological Scale score. The negative predictive value was excellent for both clinical and SPECT indices. Multivariate analysis selected only the size of hypoperfusion as an independent predictor for the functional status (P = .004) and the Canadian Neurological Scale score for mortality (P = .009). CONCLUSIONS SPECT performed within 36 hours of onset predicts clinical outcome, but different clinical and SPECT indices with threshold values should be chosen according to the relevant outcome end point.

Single session of dual-tDCS transiently improves precision grip and dexterity of the paretic hand after stroke

Background. After stroke, deregulated interhemispheric interactions influence residual paretic hand function. Anodal or cathodal transcranial direct current stimulation (tDCS) can rebalance these abnormal interhemispheric interactions and improve motor function. Objective. We explored whether dual-hemisphere tDCS (dual-tDCS) in participants with chronic stroke can improve fine hand motor function in 2 important aspects: precision grip and dexterity. Methods. In all, 19 chronic hemiparetic individuals with mild to moderate impairment participated in a double-blind, randomized trial. During 2 separate cross-over sessions (real/sham), they performed 10 precision grip movements with a manipulandum and the Purdue Pegboard Test (PPT) before, during, immediately after, and 20 minutes after dual-tDCS applied simultaneously over the ipsilesional (anodal) and contralateral (cathodal) primary motor cortices. Results. The precision grip performed with the paretic hand improved significantly 20 minutes after dual-tDCS, with reduction of the grip force/load force ratio by 7% and in the preloading phase duration by 18% when compared with sham. The dexterity of the paretic hand started improving during dual-tDCS and culminated 20 minutes after the end of dual-tDCS (PPT score +38% vs +5% after sham). The maximal improvements in precision grip and dexterity were observed 20 minutes after dual-tDCS. These improvements correlated negatively with residual hand function quantified with ABILHAND. Conclusions. One bout of dual-tDCS improved the motor control of precision grip and digital dexterity beyond the time of stimulation. These results suggest that dual-tDCS should be tested in longer protocols for neurorehabilitation and with moderate to severely impaired patients. The precise timing of stimulation after stroke onset and associated training should be defined.

Lacunar infarctions due to cholesterol emboli.

Background and Purpose: Hypertension is commonly considered the major cause of lacunar infarctions. However, in some cases, it has been suggested that lacunes could be caused by cerebral emboli from cardiac or carotid sources. Cholesterol cerebral emboli have been rarely reported as a cause of lacunes. Case Description: We describe a 79-year-old patient with a progressive multi-infarct dementia who developed transient motor aphasia and paresis of the right arm. Computed tomography showed lacunar infarcts in the right caudate nucleus, left thalamus, and left putamen, as well as an old right frontal infarction. Neuropathological examination demonstrated no prominent vascular hyalinosis, but did show multiple cholesterol emboli occluding small arteries around lacunar infarcts and leptomeningeal arteries near cortical infarcts. The cholesterol material presumably originated in the extended atheromatous changes along the aortic arch. Conclusions: Our report confirms that lacunes can be caused by cholesterol emboli in some patients. Small cerebral emboli should not be overlooked as a cause of lacunes.

Persisting Perfusion Defect in Transient Ischemic Attacks A New Clinically Useful Subgroup

BACKGROUND AND PURPOSE Cerebral infarction and prolonged regional hypoperfusion have been described in patients with transient ischemic attacks (TIAs). The aim of this study was to compare the sensitivity of single-photon emission CT (SPECT) with that of brain CT and to evaluate the clinical significance of differentiation of TIA patients with or without focal hypoperfusion. METHODS From a hospital-based population, we studied the SPECT and CT findings in 76 consecutive patients, without a stroke history, who presented with TIA in the carotid artery territory. The recorded variables were the time of SPECT, imaging (<36 or > or = 36 hours), clinical presentation, history of previous TIA(s), duration of the presenting attack (<2 or > or = 2 hours), vascular risk factors, and etiology. We used both visual and semiquantitative analyses for the SPECT evaluation. Acetazolamide challenge was not performed. RESULTS The overall SPECT sensitivity was 36% (27/76). When brain CT and SPECT were performed in the same patients, the SPECT sensitivity was significantly higher than that of CT (19/59 [32%] versus 8/59 [14%]; P=.007). The SPECT sensitivity was not dependent on the time of investigation, duration of attacks, history of TIA(s), or the clinical presentation. The vascular risk and etiologic factors were not significantly different between the patients with or without prolonged focal hypoperfusion. Logistic regression did not identify any variable to discriminate the two groups. CONCLUSIONS Despite its better sensitivity compared with CT, SPECT performed without the acetazolamide test provides no additional clinically useful information on the vascular risk factors and etiology in TIA patients.