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  • Article: Watershed infarcts in transient ischemic attack/minor stroke with > or = 50% carotid stenosis: hemodynamic or embolic?
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    ABSTRACT: Watershed ischemia is a significant cause of stroke in severe carotid disease, but its pathophysiology is unsettled. Although hemodynamic compromise has long been regarded as the main mechanism-particularly with deep watershed infarction-there is some contradictory evidence from clinical and pathological studies for a role of microembolism, thought to result from plaque inflammation. However, no study so far has directly addressed these conflicting scenarios. In 16 consecutive patients with recent transient ischemic attack/minor stroke and ipsilateral 50% to 99% carotid stenosis, we prospectively obtained (1) plaque inflammation mapping with (18)F fluorodeoxyglucose positron emission tomography; (2) brain MRI and perfusion MR; and (3) transcranial Doppler detection of microembolic signals (MES). Patients were excluded if on dual antiplatelets or with a potential cardiac source of emboli or contralateral MES. We found the expected significant relationship between (1) degree of stenosis and severity of distal hemodynamic impairment in the watershed areas; and (2) degree of in vivo plaque inflammation and rate of MES/hr. Deep watershed infarcts were present in 8 patients and MES in 8 (3 with both). There was no systematic association between the presence of deep watershed infarcts and either hemodynamic impairment or MES, but deep watershed infarcts were present only when either hemodynamic impairment or MES was present (P=0.01). This pilot study supports the idea that in symptomatic carotid disease, deep watershed infarcts result either from hemodynamic impairment secondary to severe lumen stenosis or from microembolism secondary to plaque inflammation. There was no direct evidence that both mechanisms act in synergy.
    Stroke 07/2010; 41(7):1410-6. · 5.73 Impact Factor
  • Article: Microembolism versus hemodynamic impairment in rosary-like deep watershed infarcts: a combined positron emission tomography and transcranial Doppler study.
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    ABSTRACT: Deep watershed infarcts are frequent in high-grade carotid disease and are thought to result from hemodynamic impairment, particularly when adopting a rosary-like pattern. However, a role for microembolism has also been suggested, though never directly tested. Here, we studied the relationships among microembolic signals (MES) on transcranial Doppler, rosary-like deep watershed infarcts on brain imaging, and cerebral hemodynamic compromise on positron emission tomography (PET), all in severe symptomatic carotid disease. We hypothesized that rosary-like infarcts would be significantly associated with worse hemodynamic status, independent of the presence of MES. Sixteen patients with ≥70% carotid disease ipsilateral to recent transient ischemic attack/minor stroke underwent magnetic resonance imaging including diffusion-weighted imaging, (15)O-PET, and transcranial Doppler. Mean transit time, a specific marker for hemodynamic impairment, was obtained in the symptomatic and unaffected hemispheres. Eleven of 16 patients had rosary-like infarcts (Rosary+) and 8 patients had MES. Mean transit time was significantly higher (P=0.008) in Rosary+ patients than in healthy controls (n=10), and prevalence of MES was not different between Rosary+ and Rosary- patients. Contrary to our hypothesis, however, the presence of MES within the Rosary+ subset was associated (P=0.03) with a better hemodynamic status than in their absence, with a significant (P=0.02) negative correlation between mean transit time and rate of MES/h. Contrary to mainstream understanding, rosary-like infarcts were not independent of presence and rate of MES, suggesting that microembolism plays a role in their pathogenesis, probably in association with hemodynamic impairment. Pending confirmation in a larger sample, these findings have management implications for patients with carotid disease and rosary-like infarcts.
    Stroke 08/2011; 42(11):3138-43. · 5.73 Impact Factor
  • Article: Carotid plaque inflammation is associated with cerebral microembolism in patients with recent transient ischemic attack or stroke: a pilot study.
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    ABSTRACT: Cerebral infarcts distal to carotid stenoses are thought to be caused by emboli from inflamed, destabilized plaques. We hypothesized that microembolic signals (MES) on transcranial Doppler will be associated with carotid plaque inflammation on (18)F fluorodeoxyglucose positron-emission tomography (FDG PET) in recently symptomatic patients. Sixteen patients presenting with recent (47 ± 31 days) anterior circulation transient ischemic attack or minor stroke and 50% to 99% stenosis of the ipsilateral carotid bifurcation underwent FDG PET, high-resolution black-blood carotid MRI, and transcranial Doppler for detection of MES. Patients with potential cardiac sources of emboli or contralateral MES were excluded. Regions of interest defined on the coregistered MRI were used to measure FDG standardized uptake values (with Rousset partial volume correction) from the index and contralateral carotid plaques and artery. Ipsilateral MES were detected in 7 patients (MES+ group) and absent in 8 (MES- group). There was a significant difference in index-to-contralateral plaque standardized uptake value ratio between MES+ (median, 1.05; first to third quartile, 0.96 to 1.32) and MES- (median, 0.76; first to third quartile, 0.62 to 0.94) patients (P=0.005). The interval from symptom onset to PET and percent index carotid stenosis were not different between the 2 groups (P=0.68 and P=0.48, respectively). In this sample of recently symptomatic patients with carotid stenosis, an association was found between in vivo measures of plaque inflammation detected by FDG PET and the presence of transcranial Doppler MES. These findings strengthen the notion that embolic events distal to carotid stenoses are related to plaque inflammation, and FDG PET may be useful in the investigation of culprit carotid lesions.
    Circulation Cardiovascular Imaging 09/2010; 3(5):536-41. · 5.94 Impact Factor
  • Article: Differential hemodynamic response to repetitive transcranial magnetic stimulation in acute stroke patients with cortical versus subcortical infarcts.
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    ABSTRACT: To assess the cerebral vasomotor response to ipsilesional repetitive transcranial magnetic stimulation (rTMS) on transcranial Doppler (TCD) in patients with recent ischemic stroke without carotid occlusive disease, and to compare this response in patients with cortical and subcortical infarcts. Consecutive patients with first-ever anterior circulation acute ischemic stroke (<3 days) and no extra- or intracranial arterial stenosis were prospectively recruited. Patients were divided into 2 groups: cortical infarct (CI, n = 15) and subcortical infarct (SI, n = 16). TCD cerebral blood flow velocity (CBFV) and pulsatility index were measured before and after 10-Hz suprathreshold rTMS over the dorsolateral prefrontal cortex. ANOVA showed a greater percentage increase in middle cerebral artery (MCA) CBFV in the SI group than in the CI group following rTMS (p = 0.01). The percentage change in CBFV was significantly correlated between both MCAs in SI patients but not in CI patients (r = 0.8, p < 0.001 vs. r = 0.05, p = 0.9, respectively). 10-Hz rTMS induces significant bilateral hemodynamic changes in patients with acute ischemic stroke, which appear to be less prominent and less synchronous in patients with cortical infarcts. These findings may allow optimization of the use of TMS in acute stroke.
    European Neurology 01/2010; 63(6):337-42. · 1.81 Impact Factor
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    Article: Repetitive transcranial magnetic stimulation at 1Hz and 5Hz produces sustained improvement in motor function and disability after ischaemic stroke.
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    ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a simple and non-invasive method of augmenting motor recovery after stroke, probably mediated by restoring inter-hemispheric activation balance. This placebo-controlled pilot study examined the possible benefit of stimulating the lesioned hemisphere (5-Hz rTMS) or inhibiting the contra-lesional hemisphere (1-Hz rTMS) on clinical recovery of motor function in patients with ischaemic stroke and assessed the sustainability of the response. Sixty patients with ischaemic stroke (>1 month from onset) with mild-to-moderate hemiparesis were randomized to receive 10 daily sessions of either sham rTMS, 5-Hz ipsi-lesional rTMS or 1-Hz contra-lesional rTMS, in addition to a standard physical therapy protocol. Serial assessments were made over a period of 12 weeks by the thumb-index finger tapping test (FT), Activity Index (AI) score and the modified Rankin Scale (mRS). In contrast to control patients, those receiving active rTMS as ipsi-lesional 5-Hz stimulation or 1-Hz contra-lesional stimulation showed statistically significant improvement on the FT test, AI scores and mRS score at 2 weeks, and the effect was sustained over the 12-week observation period. No significant adverse events were observed during treatment in either group. Repetitive TMS has beneficial effects on motor recovery that can be translated to clinically meaningful improvement in disability in patients with post-stroke hemiparesis, with a well-sustained effect. The similarity of inhibitory and stimulatory rTMS in producing these effects supports the inter-hemispheric balance hypothesis and encourages further research into their use in long-term neurorehabilitation programmes of patients with stroke.
    European Journal of Neurology 09/2010; 17(9):1203-9. · 3.69 Impact Factor

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