Redgrave JN, Coutts SB, Schulz UG et al. Systematic review of associations between the presence of acute ischemic lesions on

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1 6. Imaging in TIA 6.1 What type of brain imaging should be used in suspected TIA? 6.2 Which patients with suspected TIA should be referred for urgent brain imaging? Evidence Tables IMAG1: After TIA/minor stroke which modality (MRI or CT) should be used? IMAG2: Which patients with suspected TIA/minor stroke should be referred for urgent imaging Reference Study type Evidence level Numb er of patien ts Patient characteristics Intervention Comparison Length of followup Outcome measures Source of funding Redgrave JN, Coutts SB, Schulz UG et al. Systematic review of associations between the presence of acute ischemic lesions on diffusionweighted imaging and clinical predictors of early stroke risk after ischemic attack. Stroke. 2007; 38(5): Ref ID: 2627 Systematic Review last search October N=12 42 (N=19 studie s) Studies on patients with TIA comparing the results of those with positive and negative DWI Mean age range 58.5 to 73 yrs, male range 44 to 91% Delay to DWI: 6 studies less than 24 hrs, 9 studies greater than 24 hrs, 4 studies not reported. DWI positive (range of positive scans 16 to 67%) DWI negative NA Clinical and demographic prognostic indicators None reported

2 Time to scan less than 24 hrs There was a positive association between a positive DWI and motor weakness (DWI + vs 27/38 vs 52/114; OR 3.49; 95%CI 1.58 to 7.71; p=0.006), and dysphasia (10/34 vs 14/104; OR2.95 (95%CI 1.17 to 7.48; p=0.04). There were no associations between a positive DWI and age 60 yrs (NS), previous hypertension (NS), current raised blood pressure (NS), diabetes (NS), dysarthria (NS), duration of symptoms 60 mins (NS), atrial fibrillation (NS) or ipsilateral carotid stenosis 50% (NS). All studies There was a positive association between a positive DWI and motor weakness (DWI + vs DWI 151/214 vs 254/505; OR 2.20; 95%CI 1.56 to 3.10; p<0.001), dysphasia (67/220 vs 102/505; OR 2.25; 95%CI 1.57 to 3.22; p<0.001), dysarthria 43/133 vs 81/379; OR 1.73; 95%CI 1.11 to 2.68; p=0.03), duration of symptoms 60 mins (184/330 vs 321/695; OR 1.50; 95%CI 1.16 to 1.96; p=0.004), atrial fibrillation (55/249 vs 42/518; OR 2.75; 1.78 to 4.25; p<0.001) and ipsilateral carotid stenosis 50% (73/271 vs 77/563; OR 1.63; 95%CI 1.34 to 2.76; p=0.001). There were no associations between positive DWI and age 60 yrs (NS), previous hypertension (NS), current raised blood pressure (NS) or diabetes (NS). Calvet D. Management and Prospective case series 3 N=20 3 Patients admitted to a stroke unit within 48 hrs of symptom Routine investigations included MRI, 12-lead EKG, prolonged 3-lead cardiac NA 3 months outcome of onset with a diagnosis of monitoring (93%), Doppler ultrasound, patients with probable or possible TIA ECG. Patient population: Median ischemic attack time from TIA onset to first admitted to a medical management in the stroke unit. emergency departments 180 Cerebrovascular Diseases. 2007; 24(1): Ref min (IQR 90 to 540 mins). Median time from TIA onset to stroke unit admission 12 hrs (5 ID: 236 to 25). Media time from TIA onset to MRI 20 hrs (8 to 29). Acute ischemic lesions on DWI 64/203 (32%). Mean age 61 yrs, 61% male, previous TIA 9%, previous stroke 8%, motor weakness 54%, large-artery atherosclerosis 18%, small vessel disease 12% 147/207 (72%) antiplatelet therapy only Risk of stroke None reported

3 56/203 (28%) anticoagulation with full heparin dose 7/203 (3%) carotid revascualrisation Mean stay 6 days. The absolute risk of ischemic stroke was 2.0% (95%CI 0.1 to 3.9) at 48 hrs, 2.5% (0.3 to 4.7) at one week, and 3.5% (1.0 to 6.1) at 3 months. The risk of ischemic stroke or TIA was 2.5% (0.3 to 4.6) at 48 hrs, 5.0% (2.0 to 8.0) at one week, and 9.9% (5.6 to 14.1) at 3 months. The Cox analysis showed that presence of DWI abnormalities (HR 10.3; 95%CI 1.2 to 86.7; p=0.032) was independently associated with the risk of stroke at three months. Coutts SB, Simon JE, Eliasziw M et al. Triaging ischemic attack and minor stroke patients using acute magnetic resonance imaging. Annals of Neurology. 2005; 57(6): Ref ID: 2422 Prospective case series 3 N=120 Patients with minor stroke (NIHSS score of 0 to 3 or resolved hemiparesis or aphasia lasting longer than 5 mins) (N=51) and TIA (N=69) Inclusion criteria: Functional independen ce of the modified Rankin Scale (score 2) immediately before stroke or TIA onset MRI and DWI Performed within 24 hrs of symptom onset 45/120 (37.5%) underwent imaging in 6 hrs or less, 35/120 (29.2%) underwent imaging between 6 and 12 hrs, and 40/120 (33.3%) underwent imaging 12 to 24 hrs. NA 90 days IMAG1: Imaging findings IMAG2: Independent predictors of stroke/ mortality New stroke Canadian stroke charities

4 Patient population: mean age 66 yrs and 62.5% male IMAG1: *DWI 15/120 (12.5%) had a DWI lesion and intracranial vessel occlusion on the baseline MR scan. 54/120 (45%) had a DWI lesion only. 51/120 (42.5%) had neither a DWI lesion nor vessel occlusion. No patients with an intracranial vessel occlusion had a negative DWI. 7/51 (13.7%) patients with a DWI lesion had a diagnosis of stroke. The presence of a DWI lesion was related to whether the patient had residual signs at 24 hrs (p<0.001). Patients with a DWI lesion were more likely to have a TOAST classification of large-artery disease in comparison with patients with a negative DWI (DWI present and occlusion absent 25.9%, DWI present and occlusion present 53.3% and DWI negative 7.8%; p<0.001) IMAG2: *New stroke occurrence 14/120 (11.7%) patients had a new stroke at 90-day follow-up. Of these nine were in the first 48hrs. A multivariable analysis identified baseline NIHSS and blood glucose greater than 7mmol/L were identified as confounders. The adjusted (for NIHSS and glucose) risk estimates of having a stroke within 90 days was 14.7% for patients with a DWI lesion and 4.2% for patients without a DWI lesion (NS). The risk of new stroke was 30.8% in the presence of intracranial vessel occlusion and 7.6% without occlusion (p=0.01). The adjusted Kaplan-Meier 90-days risks were 4.3% (no DWI lesion and no vessel occlusion), 10.8% (DWI lesion no vessel occlusion) and 32.6% (DWI lesion and vessel occlusion) (p=0.02). Patient with a DWI lesion were 2.6 more likely to have a stroke (NS). Patients with a DWI lesion and vessel occlusion were 8.9 times more likely to have a new stroke (95%CI 1.6 to 4.9; p=0.01). *Functional dependence The mrs at follow-up (adjusting for baseline scores) were 1.9% (no DWI lesion), 6.2% (DWI lesion no vessel occlusion) and 21.0% (DWI lesion and vessel occlusion) (p=0.04). Purroy F, Montaner J, Rovira A et al. Higher risk of further vascular events among ischemic attack patients with Prospective case series 3 N=8 7 (4 patie nts exclu ded after MRI) Patients with TIA who were seen by a neurologist in the emergency room within 24 hrs Patient population: Mean age 66.4 yrs, male 54.2%, median duration of symptoms 30 mins, previous stroke 15 (18.1%), hypertension 45 (54.2) DWI, MRI and CT Time to scan maximum seven days Blinding not reported NA Mea n 389 days IMAG1: Imaging findings IMAG2: Predictors of new stroke/ death None reported

5 diffusionweighted imaging acute ischemic lesions. Stroke. 2004; 35(10): Ref ID: 1198 IMAG1: *TIA definition A brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting < 1 hr *DWI According to the new definition of TIA (< 60 minutes) 55.4% of patients met this criterion. Normal DWI was present in 36.4% of patients. 36.4% of patients met the new definition for TIA. *DWI, MR and CT Cranial CT was performed within 24 hrs of symptom onset showed a chronic ischemic infarct in 18 (21.7%) of patients, compared with 27 (32.5%) patients had a chronic ischemic infarction on cranial MR. DWI demonstrated acute ischemic lesions in 27 (72.5%) of patients. *Follow-up Patients were followed-up for a mean of 389 days. 16 (19.3%) patients had new cerebral ischemic event in this time period. Two patients died (one ischemic stroke and one intracranial haemorrhage). 46 patients with a short duration of symptoms (< 60 mins) presented 6 cerebral ischemic events (14%) and seven vascular events (16.3%). Eight cerebral ischemic events (14.3%) and ten vascular events (17.9%) appeared in 56 patients who fulfilled the neuroimaging criteria (DWI normality). Only three cerebral ischemic events (10.7%) with no other vascular event was recorded in the 28 patients with the duration of symptoms less than 60 mins and without positive DWI. Among ten patients with symptoms lasting more than 60 mins and with DWI abnormalities, cerebral ischemic event developed in four patients (40%) and five cases (50%) had a vascular event. IMAG 2: *Variables associated with new cerebral ischemic and vascular events during follow-up The univariate analysis past history of stroke, duration of symptoms > 60 mins associated with DWI abnormaity, and large-artery occlusive disease were associated with an increased risk of further cerebral ischemic events (all p<0.05). Age, past history of previous, duration of symptoms > 60 mins or DWI abnormality, and large-artery occlusive disease was associated with future major vascular disease (all p<0.05). *Independent predictors of new cerebral ischemic or vascular events (multivariate analyses) Duration of symptoms 60 mins with DWI abnormality (HR 5.02; 95%CI 1.37 to 18.30; p=0.0146) and large artery occlusive disease (HR 4.22; 95%CI 4.22; 95%CI 1.17 to 15.22; p=0.0276) were

6 independent predictors of further cerebral ischemic events and also for vascular events during follow-up (HR 3.77; 95%CI 3.77; 95%CI 1.01 to 25.91; p=0.038) and HR (5.33; 95%CI 1.17 to 27.05; p=0.031). Prabhakaran S, Chong JY, Retrospective case series 3 N=196 Patients with TIA or stroke TIA patients with normal DWI results TIA patients 90 days Recurrent TIA or stroke National Institutes of Health Sacco RL. TIA Exclusion criteria: No MRI within 48 hrs with Predictors of Impact of N=146 N=109 abnormal recurrence TIA patients: 37/146 (25%) had lesions on DWI abnormal Acute DWI and 109/146 (75%) normal DWI. results diffusionweighted mic Patient population: ische (TSI) imaging results stroke TIA with normal DWI results mean age 67.4, N=37 on short-term outcome following and with infarcti male 33%, white 35%, prior TIA 32%*, motor symptoms 39%, mean NIHSS score at 24 hrs 0*, duration of TIA > 1 hr 27%*, moderate to Ischemic stroke on severe stenosis or occlusion 15%*, mean ischemic attack. (DWI length of stay 3 days* N=50 confir TIA with abnormal DWI results - mean age Archives of med) 69.5, male 8%, white 32%, prior TIA 11%*, Neurology. N=50 motor symptoms 68%, mean NIHSS score at 2007; (from 24 hrs 0*, duration of TIA > 1 hr 60%*, 64(8): moderate to severe stenosis or occlusion admis sions) 49%*, mean length of stay 5 days* Ischemic stroke - mean age 66.5, male 44%, white 28%, prior TIA 14%*, motor symptoms 76%, mean NIHSS score at 24 hrs 6*, moderate to severe stenosis or occlusion 40%*, mean length of stay 7 days* * significant difference Rate of recurrent TIA or stroke 3/109 (2.8%) of TIA patients without lesions on DWI had a recurrent TIA and there were no strokes. Of the 50 ischemic stroke patients, one (2.0%) had a recurrent ischemic stroke (NIHSS score increased from 5 to 9). In contrast, there were 4/37 recurrent TIAs and 6/37 ischemic strokes (NIHSS 3 to 13) in TIA patients with infarction. Logistic regression analysis (adjusted) showed that TIA with infarction was an independent predictor of recurrent TIA or stroke (OR 11.2; p<0.01). When only patients with mild strokes or TIA (NIHSS < 5) were included (N=184), TIA with infarction was an independent predictor of inpatient recurrence (OR (adjusted) 10.6; p=0.01).

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