Akram A Hosseini

Carotid plaque hemorrhage on magnetic resonance imaging strongly predicts recurrent ischemia and stroke.

There is a recognized need to improve selection of patients with carotid artery stenosis for carotid endarterectomy (CEA). We assessed the value of magnetic resonance imaging (MRI)‐defined carotid plaque hemorrhage (MRIPH) to predict recurrent ipsilateral cerebral ischemic events, and stroke in symptomatic carotid stenosis.Objective There is a recognized need to improve selection of patients with carotid artery stenosis for carotid endarterectomy (CEA). We assessed the value of magnetic resonance imaging (MRI)-defined carotid plaque hemorrhage (MRIPH) to predict recurrent ipsilateral cerebral ischemic events, and stroke in symptomatic carotid stenosis. Methods One hundred seventy-nine symptomatic patients with ≥50% stenosis were prospectively recruited, underwent carotid MRI, and were clinically followed up until CEA, death, or ischemic event. MRIPH was diagnosed if the plaque signal intensity was >150% that of the adjacent muscle. Event-free survival analysis was done using Kaplan–Meier plots and Cox regression models controlling for known vascular risk factors. We also undertook a meta-analysis of reported data on MRIPH and recurrent events. Results One hundred fourteen patients (63.7%) showed MRIPH, suffering 92% (57 of 62) of all recurrent ipsilateral events and all but 1 (25 of 26) future strokes. Patients without MRIPH had an estimated annual absolute stroke risk of only 0.6%. Cox multivariate regression analysis proved MRIPH as a strong predictor of recurrent ischemic events (hazard ratio [HR] = 12.0, 95% confidence interval [CI] = 4.8–30.1, p < 0.001) and stroke alone (HR = 35.0, 95% CI = 4.7–261.6, p = 0.001). Meta-analysis of published data confirmed this association between MRIPH and recurrent cerebral ischemic events in symptomatic carotid artery stenosis (odds ratio = 12.2, 95% CI = 5.5–27.1, p < 0.00001). Interpretation MRIPH independently and strongly predicts recurrent ipsilateral ischemic events, and stroke alone, in symptomatic ≥50% carotid artery stenosis. The very low stroke risk in patients without MRIPH puts into question current risk–benefit assessment for CEA in this subgroup. ANN NEUROL 2013;73:774–784

Risk factors associated with cerebrovascular recurrence in symptomatic carotid disease: a comparative study of carotid plaque morphology, microemboli assessment and the European Carotid Surgery Trial risk model.

Background The European Carotid Surgery Trial (ECST) risk model is a validated tool for predicting cerebrovascular risk in patients with symptomatic carotid disease. Carotid plaque hemorrhage as detected by MRI (MRIPH) and microembolic signals (MES) detected by transcranial Doppler (TCD) are 2 emerging modalities in assessing instability of the carotid plaque. The aim of this study was to assess the strength of association of MES and MRIPH with cerebrovascular recurrence in patients with symptomatic carotid artery disease in comparison with the ECST risk prediction model. Methods and Results One hundred and thirty‐four prospectively recruited patients (mean [SD]: age 72 [9.8] years, 33% female) with symptomatic severe (50% to 99%) carotid stenosis underwent preoperative TCD, MRI of the carotid arteries to assess MES, PH, and the ECST risk model. Patients were followed up until carotid endarterectomy, recurrent cerebral event, death, or study end. Event‐free survival analysis was done using backward conditional Cox regression analysis. Of the 123 patients who had both TCD and MRI, 82 (66.7%) demonstrated PH and 46 (37.4%) had MES. 37 (30.1%) cerebrovascular events (21 transient ischemic attacks, 6 amaurosis fugax, and 10 strokes) were observed. Both carotid PH (HR=8.68; 95% CI 2.66 to 28.40, P<0.001) as well as MES (HR=3.28; 95% CI 1.68 to 6.42, P=0.001) were associated with cerebrovascular event recurrence. Combining MES and MRIPH improved the strength of association (HR=0.74, 95% CI 0.65 to 0.83; P<0.001). The ECST risk model was not associated with recurrence (HR=0.86; 95% CI 0.45 to 1.65; P=0.65). Conclusions The presence of carotid plaque hemorrhage is better associated with recurrent cerebrovascular events in patients with symptomatic severe carotid stenosis than the presence of microembolic signals; combining MES and MRIPH, further improves the association while the ECST risk score was insignificant.

Lower prevalence of carotid plaque hemorrhage in women, and its mediator effect on sex differences in recurrent cerebrovascular events.

Background and Purpose Women are at lower risk of stroke, and appear to benefit less from carotid endarterectomy (CEA) than men. We hypothesised that this is due to more benign carotid disease in women mediating a lower risk of recurrent cerebrovascular events. To test this, we investigated sex differences in the prevalence of MRI detectable plaque hemorrhage (MRI PH) as an index of plaque instability, and secondly whether MRI PH mediates sex differences in the rate of cerebrovascular recurrence. Methods Prevalence of PH between sexes was analysed in a single centre pooled cohort of 176 patients with recently symptomatic, significant carotid stenosis (106 severe [≥70%], 70 moderate [50–69%]) who underwent prospective carotid MRI scanning for identification of MRI PH. Further, a meta-analysis of published evidence was undertaken. Recurrent events were noted during clinical follow up for survival analysis. Results Women with symptomatic carotid stenosis (50%≥) were less likely to have plaque hemorrhage (PH) than men (46% vs. 70%) with an adjusted OR of 0.23 [95% CI 0.10–0.50, P<0.0001] controlling for other known vascular risk factors. This negative association was only significant for the severe stenosis subgroup (adjusted OR 0.18, 95% CI 0.067–0.50) not the moderate degree stenosis. Female sex in this subgroup also predicted a longer time to recurrent cerebral ischemic events (HR 0.38 95% CI 0.15–0.98, P = 0.045). Further addition of MRI PH or smoking abolished the sex effects with only MRI PH exerting a direct effect. Meta-analysis confirmed a protective effect of female sex on development of PH: unadjusted OR for presence of PH = 0.54 (95% CI 0.45–0.67, p<0.00001). Conclusions MRI PH is significantly less prevalent in women. Women with MRI PH and severe stenosis have a similar risk as men for recurrent cerebrovascular events. MRI PH thus allows overcoming the sex bias in selection for CEA.

MR imaging-detected carotid plaque hemorrhage is stable for 2 years and a marker for stenosis progression.

BACKGROUND AND PURPOSE: MR imaging–detected carotid plaque hemorrhage is associated with an increased risk of recurrent ischemic cerebrovascular events and could be an indicator of disease progression; however, there are limited data regarding the dynamics of the MR imaging–detected carotid plaque hemorrhage signal. We assessed the temporal change of this signal and its impact on carotid disease progression. MATERIALS AND METHODS: Thirty-seven symptomatic patients with 54 carotid stenoses of >30% on sonography underwent serial MR imaging during 24 months. A signal-intensity ratio of >1.5 between the carotid plaque and adjacent muscle was defined as plaque hemorrhage, and a change in signal-intensity ratio of >0.31 between time points was considered significant. Sixteen patients underwent ≥2 carotid sonography scans to determine the peak systolic velocities and degree of stenosis with time. RESULTS: Of the 54 carotids, 28 had the presence of hyperintense signal on an MR imaging sequence (PH+) and 26 had the absence of hyperintense signal on an MR imaging sequence (PH−) at baseline. The signal-intensity ratio was stable in 33/54 carotid plaques, but 39% showed a change. Plaque hemorrhage classification did not change in 87% of carotid plaques, but 4 became PH+, and 3, PH−. As a group, PH+ carotids did not change significantly in signal-intensity ratio (P = .585), whereas PH− showed an increased signal-intensity ratio at 24.5 months (P = .02). In PH+ plaques, peak systolic velocities significantly increased by 22 ± 39.8 cm/s from baseline to last follow-up sonography (Z = 2.427, P = .013). CONCLUSIONS: During 2 years, MR imaging–detected carotid plaque hemorrhage status remained stable in most (87%) cases with 4 (7%) incident plaque hemorrhages. PH+ plaques were associated with increased flow velocity during the follow-up period.

Lesion Topography and Microscopic White Matter Tract Damage Contribute to Cognitive Impairment in Symptomatic Carotid Artery Disease

Subcortical disconnection of cognitive neural networks is a key mechanism of cognitive impairment in patients with probable vascular cognitive disorder.

Magnetic Resonance Imaging Plaque Hemorrhage for Risk Stratification in Carotid Artery Disease With Moderate Risk Under Current Medical Therapy

Background and Purpose— Magnetic resonance imaging (MRI)–defined carotid plaque hemorrhage (MRIPH) can predict recurrent cerebrovascular ischemic events in severe symptomatic carotid stenosis. It is less clear whether MRIPH can improve risk stratification despite optimized medical secondary prevention in those with moderate risk. Methods— One-hundred fifty-one symptomatic patients with 30% to 99% carotid artery stenosis (median age: 77, 60.5% men) clinically deemed to not benefit from endarterectomy were prospectively recruited to undergo MRI and clinical follow-up (mean, 22 months). The clinical carotid artery risk score could be evaluated in 88 patients. MRIPH+ve was defined as plaque intensity >150% that of adjacent muscle. Survival analyses were performed with recurrent infarction (stroke or diffusion-positive cerebral ischemia) as the main end point. Results— Fifty-five participants showed MRIPH+ve; 47 had low, 36 intermediate, and 5 high carotid artery risk scores. Cox regression showed MRIPH as a strong predictor of future infarction (hazard ratio, 5.2; 95% confidence interval, 1.64–16.34; P=0.005, corrected for degree of stenosis), also in the subgroup with 50% to 69% stenosis (hazard ratio, 4.1; 95% confidence interval, 1–16.8; P=0.049). The absolute risk of future infarction was 31.7% at 3 years in MRIPH+ve versus 1.8% in patients without (P<0.002). MRIPH increased cumulative risk difference of future infarction by 47.1% at 3 years in those with intermediate carotid artery risk score (P=0.004). Conclusions— The study confirms MRIPH to be a powerful risk marker in symptomatic carotid stenosis with added value over current risk scores. For patients undergoing current secondary prevention medication with clinically uncertain benefit from recanalization, that is, those with moderate degree stenosis and intermediate carotid artery risk scores, MRIPH offers additional risk stratification.

Mesiotemporal atrophy and hippocampal diffusivity distinguish amnestic from non‐amnestic vascular cognitive impairment

The role of clinical factors, cerebral infarcts and hippocampal damage in vascular cognitive impairment (VCI) subtypes remains unclear.

PO108 Susac syndrome: a case for early, aggressive and sustained treatment

Introduction We report a case of Susac syndrome, initially suspected to be multiple sclerosis, and advocate diagnostic caution and high suspicion. We describe a successful therapeutic approach comprising corticosteroids, intra-venous immunoglobulin and cyclophosphamide for encephalopathic relapse of Susac syndrome. Case report A 56 year old woman presented with headache, visual disturbance, chest wall hypoaesthesia and unsteadiness that was initially thought due to multiple sclerosis. Over the course of her disease she developed bilateral tinnitus and hyperacusis, later accompanied by hearing loss. Brain MRI showed white matter changes with a propensity for the corpus callosum. Full field retinal fluorescein angiography displayed multiple branch retinal artery occlusions with retinal vasculitis. Pure tone audiometry revealed impairment in the low to mid-range frequency bands bilaterally. Disease course was complicated by encephalopathic relapse, presenting with seizure. Repeated courses of immunotherapy (pulses of intra-venous methylprednisolone, cycles of intra-venous immunoglobulins and cyclophosphamide) have suppressed symptoms and halted disease progression. Conclusion Susac syndrome is a key differential diagnosis of neuro-inflammatory disease. International multi-centre trials are required to establish optimal therapeutic strategies. Meanwhile, we find an aggressive, sustained regime of monthly immunoglobulin and cyclophosphamide for at least six months to maintain recovery in the encephalopathic form of Susac Syndrome.

PO191 Diffuse psoriatic exacerbation following immunoglobulin administration

Introduction Immunoglobulin therapy has been associated with eczematous, erythematous, allergic rashes, but an association with psoriatic exacerbations is unreported. Case A 51 year old man with quiescent plaque psoriasis presented with progressive ascending quadriparesis over 48 hours, preceded by a diarrhoeal illness. He was diagnosed with an acute inflammatory demyelinating polyneuropathy, as confirmed by electrophysiology and raised CSF protein. Approximately 3 weeks after initial course of intra-venous immunoglobulin (0.4 g/kg for 5 days) he was noted to have a mild palmar rash considered negligible. A second cycle of treatment was considered in view of his extensive on-going disability, functional dependence due to tetraplegia, with slow meaningful response to initial treatment. Approximately one week subsequent to the second cycle, a generalised erythematous and pustular rash with widespread exfoliation, suggestive of either a drug rash or generalised pustular psoriasis occurred. Skin biopsy confirmed psoarisis. This required extensive and prolonged dermatological treatment including emollients, antibiotics and acitretin. In the face of distressing erythroderma and complicating infection, neurological rehabilitation has been remarkably delayed. Conclusion We report the first case of a widespread, exfoliative and erythematous psoriatic exacerbation following immunoglobulin administration. Serious dermatological complications should be considered in patients with pre-existing psoriasis prior to immunoglobulin administration.

PO179 Aggressive disseminated intracranial anaplastic astrocytoma

Case A 21-year-old male immigrant from Afghanistan presented with seizures 2 years previously. MRI brain was suggestive of a possible low-grade glioma affecting the right temporal lobe. After 2 years, he re-presented with symptoms of headache, intermittent pyrexia, raised intracranial pressure (opening pressure of >42 cm/H2O) requiring ventriculoperitoneal shunt to preserve his vision. MRI head revealed slight progression in appearance within the right medial temporal lobe and extension into the right cerebral peduncle with enhancement of the basal meninges as well as 7th and 8th nerve complexes. CSF consistently showed two-digit lymphocytes, with raised protein and moderately reduced glucose ratio. Large CSF samples for cytology and flow-cytometry, Acid-Fast-Bacilli, and IgG subtypes remained negative. He had lymphopaenia. CT body/PET scans revealed no lymphadenopathy. Originally, tuberculosis was considered and quadruple anti-tuberculosis therapy was given along with oral Prednisolone. His first negative tuberculosis culture after 6 weeks coincided with increasing widespread leptomeningeal spread into the intradural spinal cord. Brain biopsy from the basal leptomeninges and temporal lobe confirmed anaplastic astrocytoma. Conclusion Anaplastic astrocytoma can present as aggressive and diffuse leptomeningeal brain and spinal disease mimicking CNS tuberculosis. Persistently negative Acid-Fast-Bacilli from the CSF samples should prompt consideration of less typical primary brain tumours.