Serum Neurofilaments in Motor Neuron Disease and Their Utility in Differentiating ALS, PMA and PLS.

Neurofilament levels are elevated in many neurodegenerative diseases and have shown promise as diagnostic and prognostic biomarkers in Amyotrophic Lateral Sclerosis (ALS), the most common form of Motor Neuron Disease (MND). This study assesses serum neurofilament light (NFL) and neurofilament heavy (NFH) chain concentrations in patients with ALS, other variants of motor neuron disease such as Progressive Muscular Atrophy (PMA) and Primary Lateral Sclerosis (PLS), and a range of other neurological diseases. It aims to evaluate the use of NFL and NFH to differentiate these conditions and for the prognosis of MND disease progression. NFL and NFH levels were quantified using electrochemiluminescence immunoassays (ECLIA). Both were elevated in 47 patients with MND compared to 34 patients with other neurological diseases and 33 healthy controls. NFL was able to differentiate patients with MND from the other groups with a Receiver Operating Characteristic (ROC) curve area under the curve (AUC) of 0.90 (p < 0.001). NFL correlated with the rate of disease progression in MND (rho 0.758, p < 0.001) and with the ALS Functional Rating Scale (rho -0.335, p = 0.021). NFL levels were higher in patients with ALS compared to both PMA (p = 0.032) and PLS (p = 0.012) and were able to distinguish ALS from both PMA and PLS with a ROC curve AUC of 0.767 (p = 0.005). These findings support the use of serum NFL to help diagnose and differentiate types of MND, in addition to providing prognostic information to patients and their families.

Systematic Review and Meta-Analysis of Diagnostic Agreement in Suspected TIA.

OBJECTIVE: To determine the interrater variability for TIA diagnostic agreement among expert clinicians (neurologists/stroke physicians), administrative data, and nonspecialists. METHODS: We performed a meta-analysis of studies from January 1984 to January 2019 using MEDLINE, EMBASE, and PubMed. Two reviewers independently screened for eligible studies and extracted interrater variability measurements using Cohen's kappa scores to assess diagnostic agreement. RESULTS: Nineteen original studies consisting of 19,421 patients were included. Expert clinicians demonstrate good agreement for TIA diagnosis (κ = 0.71, 95% confidence interval [CI] = 0.62-0.81). Interrater variability between clinicians' TIA diagnosis and administrative data also demonstrated good agreement (κ = 0.68, 95% CI = 0.62-0.74). There was moderate agreement (κ = 0.41, 95% CI = 0.22-0.61) between referring clinicians and clinicians at TIA clinics receiving the referrals. Sixty percent of 748 patient referrals to TIA clinics were TIA mimics. CONCLUSIONS: Overall agreement between expert clinicians was good for TIA diagnosis, although variation still existed for a sizeable proportion of cases. Diagnostic agreement for TIA decreased among nonspecialists. The substantial number of patients being referred to TIA clinics with other (often neurologic) diagnoses was large, suggesting that clinicians, who are proficient in managing TIAs and their mimics, should run TIA clinics.

A Neurodisparity Index of Nationwide Access to Neurological Health Care in Northern Ireland.

Nationwide disparities in managing neurological patients have rarely been reported. We compared neurological health care between the population who reside in a Health and Social Care Trust with a tertiary neuroscience center and those living in the four non-tertiary center Trusts in Northern Ireland. Using the tertiary center Trust population as reference, neurodisparity indices (NDIs) defined as the number of treated patients resident in each Trust per 100,000 residents compared to the same ratio in the tertiary center Trust for a fixed time period. NDIs were calculated for four neurological pathways-intravenous thrombolysis (iv-tPA) and mechanical thrombectomy (MT) for acute ischemic stroke (AIS), disease modifying treatment (DMT) in multiple sclerosis (MS) and admissions to a tertiary neurology ward. Neurological management was recorded in 3,026 patients. Patients resident in the tertiary center Trust were more likely to receive AIS treatments (iv-tPA and MT) and access to the neurology ward (p < 0.001) than patients residing in other Trusts. DMT use for patients with MS was higher in two non-tertiary center Trusts than in the tertiary center Trust. There was a geographical gradient for MT for AIS patients and ward admissions. Averaged NDIs for non-tertiary center Trusts were: 0.48 (95%CI 0.32-0.71) for patient admissions to the tertiary neurology ward, 0.50 (95%CI 0.38-0.66) for MT in AIS patients, 0.78 (95%CI 0.67-0.92) for iv-tPA in AIS patients, and 1.11 (95%CI 0.99-1.26) for DMT use in MS patients. There are important neurodisparities in Northern Ireland, particularly for MT and tertiary ward admissions. Neurologists and health service planners should be aware that geography and time-dependent management of neurological patients worsen neurodisparities.

Secular trends in disease modifying treatment and expenditure in multiple sclerosis: A longitudinal population study in the north of Ireland.

BACKGROUND: The epidemiology of multiple sclerosis (MS) is important for planning disease modifying therapy (DMT). Secular changes in the use of DMT in MS can guide future service development. METHODS: A population study of the prevalence of multiple sclerosis was completed in the west of Northern Ireland - a defined geographic area making up the Western Health and Social Care Trust (WHSCT). The use, category and cost of DMT for the MS population in the WHSCT were measured over 11 years. RESULTS: The WHSCT had a recorded prevalence of MS of 238.4/100,000 (95%CI 221.5-256.5) in 2018. DMT use increased over threefold in 11 years. Four hundred and nine (57%) of 720 MS patients were taking a DMT by 2018. The annual expenditure of DMT drugs had increased sixfold over ten years to £5,301,198 in 2018 (using 2018 prices), reflecting both an increase in DMT use and a switch to more intensive DMTs. Younger MS patients were more likely to be taking a DMT (P<0.001). CONCLUSION: DMT use and cost have been increasing among the MS population in the Northern Ireland. There has been a temporal switch to more efficacious DMTs. Future research should monitor the cost-effectiveness and equity of treatment of MS patients.

Stroke scan agnosia - What radiologists may not see.

OBJECTIVE: Neuroimaging helps neurologists make accurate diagnoses. We used a multidisciplinary review system to search for perceptual discrepancies in stroke lesions. We sought to identify recurrent pitfalls in the detection of neuroimaging stroke lesions. PATIENTS AND METHODS: Patients were selected from a neuroimaging database of second opinions if cerebrovascular lesions had been missed at initial reporting. Patient demographics, scanning modality and stroke type were recorded. RESULTS: A neuroradiologist second opinion was provided for 1336 patients. Forty-four patients, 18 women and 26 men, mean age 59.9 (SD 14.2) years, were identified in whom a vascular lesion was not detected on initial reporting. The lesions included cerebellar infarcts in 17 patients (bilateral in 7), pontine infarction/ischaemia (n=5), pontine and cerebellar lesions (n=1) and spinal infarction (n=1). Supratentorial infarction occurred in 10 patients of which 3 were thalamic infarcts. Vessel abnormalities were present in 8 patients (hyperdense vessel n=3, dissection n=3, middle cerebral artery occlusion on CTA n=1 and cerebral venous sinus thrombosis n=1). Convexity subarachnoid hemorrhage was missed and a subdural hematoma was not identified in one patient. In 10 (23 %) patients the missed lesions occurred solely on CT brain scanning. The missed lesions were symptomatic in 28 (64 %) patients and presentations were acute in 14 (32 %) patients. CONCLUSION: Some cerebrovascular lesions are prone to perceptual errors with CT and MRI brain scanning. Radiologists and neurologists should be aware that posterior fossa lesions (particularly in the cerebellum and pons) and hyperdense vessel signs may be missed. Better identification of radiological cerebrovascular lesions should enhance management of acute and chronic stroke patients.

Country-Wide Analysis of Systemic Factors Associated With Acute Ischemic Stroke Door to Needle Time.

Objective: Pre-hospital, in-hospital, and patient factors are associated with variation in door to needle (DTN) time in acute ischemic stroke (AIS). Publications are usually from large single centers or multicenter registries with less reporting on national results. Materials and methods: All AIS patients treated with intravenous tissue plasminogen activator (iv-tPA) over 4 years (2013-2016) in Northern Ireland were recorded prospectively, including patient demographics, pre-hospital care, thrombolysis rate, and DTN time. Logistic regression was performed to identify factors associated with DTN time. Results: One thousand two hundred and one patients from 10,556 stroke admissions (11.4%) were treated with iv-tPA. Median NIHSS was 10 (IQR 6-17). Median DTN time was 54 min (IQR 36-77) with 61% treated < 60 min from arrival at hospital. National thrombolysis numbers increased over time with improving DTN time (P = 0.002). Arrival method at hospital (ambulance OR 2.3 CI1.4-3.8) pre-alert from ambulance (pre-alert OR = 5.3 CI3.5-8.1) and time of day (out of hours, n = 650, OR 0.20 CI 0.22-0.38) all P < 0.001, were the independent factors in determining DTN time. Variation in DTN time between centers occurred but was unrelated to volume of stroke admissions. Conclusion: Ambulance transport with pre-hospital notification and time of day are associated with shorter DTN time on a national level. Most thrombolysis was delivered outside of normal working hours but these patients are more likely to experience treatment delays. Re-organization of stroke services at a whole system level with emphasis on pre-hospital care and design of stroke teams are required to improve quality and equitable care in AIS nationally.

Radiological Eye Deviation as a Predictor of Large Vessel Occlusion in Acute Ischaemic Stroke.

BACKGROUND: Detection of large vessel occlusion (LVO) is required for endovascular therapy in acute ischemic stroke (AIS) but CT angiography (CTA) is not always performed at primary stroke centers. Eye deviation on CT brain has been associated with improved stroke detection, but comparisons with angiographic status have been limited. This study sought to determine if radiological eye deviation was associated with LVO. METHODS: All AIS patients given intravenous thrombolysis who had acute CTA performed in 2 stroke units were reviewed over 2013-2015 for the presence of LVO. Eye deviation was determined by 2 clinicians blinded to LVO status. Logistic regression was performed to determine which factors predicated LVO. RESULTS: Total 195 AIS patients with acute CTA were identified; 124 (64%) had LVO. Median age was 72 (IQR 64-82) years, median National Institutes of Health Stroke Scale (NIHSS) was 12 (IQR 7-14). LVO patients had a higher NIHSS (15 versus 7, p < .01) and were more likely to have eye deviation on CT brain (71% versus 22.5%, p < .01). Logistic regression confirmed NIHSS score and eye deviation were associated with LVO, with odds ratios of 1.15 (per point) and 5.13 respectively. NIHSS less than equal to 11 gave greatest sensitivity (78.5%) and specificity (76.1%) for LVO with a positive predictive value of 84.7%. Eye deviation was similar with sensitivity 71%, specificity 77.5%, and 84.6%. CONCLUSIONS: Eye deviation on CT brain is strongly associated with LVO. Presence of eye deviation on CT should alert clinicians to probability of LVO and for formal angiographic testing if not already performed.

The value of neuroimaging team meetings for patients in a district general hospital.

Neuroradiologists provide quality-assured neuroimaging -reports. We developed the use of a neuroimaging team meeting to provide second-opinion reporting by neuroradiologists on neuroimaging that had previously been reported by general -radiologists. Neuroimaging from selected patients was reviewed at the meeting. Where there were discrepancies between an original report from a general radiologist and the report obtained from the meeting involving a neuroradiologist, we classified the discrepancies, recorded the scan modality -involved and used the data to assess temporal trends in discrepancy rates. Over 4 years, 562 patients (312 women, 250 men, mean age 50.6 [SD 17.3] years) were studied. Agreement occurred for 396 (70.5%) patients. Discrepancies that were not clinically important occurred for 60 (10.7%) patients. Clinically important discrepancies were found for 106 (18.9%) patients: missed lesions for 47 (8.3%) patients and misinterpretations for 59 (10.5%) patients. Cerebrovascular disease was the most common reason for a recommendation of neuroimaging review at a meeting. Scan modality did not influence the frequency of discrepancies. Discrepancy rates decreased with time (chi-squared test for linear trend p=0.015), while the frequency of neuroradiologists' recommendations for new investigations was stable at one in seven patients. Neuroimaging team meetings can facilitate improvements in neurology diagnoses.

Diagnostic test results in primary CNS vasculitis: A systematic review of published cases.

BACKGROUND: Primary CNS vasculitis (PCNSV) can be diagnosed using cerebral angiography or histopathology combined with clinical features. The original diagnostic criteria, which weigh each test equally, have not been validated. Limited sensitivity and specificity for biopsy and angiography are recognized. We systematically reviewed results of diagnostic tests performed in patients with an ultimate diagnosis of PCNSV. METHODS: We searched the OVID Medline database and bibliographies for original cases of PCNSV. We recorded demographics, diagnostic tests used, and assessed agreement between angiography and biopsy when both tests were performed. We also recorded MRI and CSF results. RESULTS: We found 701 original cases with PCNSV diagnosed with angiography or pathology. A total of 269 patients (38.4%) had both cerebral angiography and histopathologic testing (biopsy/postmortem). Classic angiographic features of vasculitis were associated with pathologic confirmation in just 32 patients (4.6%). Seventy-four patients (10.6%) with any abnormality on angiography had a normal biopsy, and 99 patients (14.1%) with abnormal biopsies had normal angiography. Brain MRI was abnormal in 505/541 patients (93.3%) and CSF was abnormal in 360/484 patients (74.4%). Increasing use of angiography and decreasing histopathologic testing were found over time. CONCLUSIONS: Cerebral angiography and pathologic tissue examination were undertaken in a minority of published cases with a diagnosis of PCNSV. When both diagnostic tests were performed, disagreement between them was more than 5 times more likely than agreement. Diagnostic criteria for PCNSV may require revision to classify the clinical, pathologic, and radiologic features of this condition more accurately.

Stroke Laterality Bias in the Management of Acute Ischemic Stroke.

BACKGROUND: Little is known of the impact of stroke laterality on the management process and outcome of patients with acute ischemic stroke (AIS). METHODS: Consecutive patients admitted to a general hospital over 1 year with supratentorial AIS were eligible for inclusion in the study. Baseline characteristics and risk factors, delays in hospital admission, imaging, intrahospital transfer to an acute stoke unit, stroke severity and classification, length of hospital admission, as well as 10-year mortality were measured and compared among right and left hemisphere AIS patients. RESULTS: There were 141 patients (77 men, 64 women; median age 73 [interquartile range 63-79] years), There were 71 patients with left hemisphere AIS and 70 with right hemisphere AIS. Delays to hospital admission from stroke onset to neuroimaging were similar among right and left hemisphere AIS patients. Delay in transfer to an acute stroke unit (ASU) following hospital admission was on average 14 hours more for right hemisphere compared to left hemisphere AIS patients (P = .01). Laterality was not associated with any difference in 10-year survival. CONCLUSIONS: Patients with mild and nondominant AIS merit particular attention to minimize their intrahospital transfer time to an ASU.

Collateral flow predicts outcome after basilar artery occlusion: The posterior circulation collateral score.

BACKGROUND AND AIM: Our aim was to assess the prognostic value of a semiquantitative computed tomography angiography-based grading system, for the prediction of outcome in patients with acute basilar artery occlusion, based on the presence of potential collateral pathways on computed tomography angiography: the posterior circulation collateral score (PC-CS). METHODS: One hundred forty-nine patients with acute basilar artery occlusion from the Basilar Artery International Cooperation Study were included. We related poor outcome at one month, defined as a modified Rankin scale score of 4 or 5, or death to collateral flow with Poisson regression. We used a 10 points grading system to quantify the potential for collateral flow in the posterior communicating arteries and the cerebellar arteries. Additionally, the relation between the presence and size of posterior communicating arteries and outcome was analyzed. RESULTS: Thirty-six patients had poor (PC-CS: 0-3), 59 patients intermediate (PC-CS: 4-5), and 54 patients good (PC-CS: 6-10) collaterals. Multivariable analyses showed a statistically significant lower risk of poor outcome in patients with a good PC-CS than in patients with a poor PC-CS (risk ratio (RR): 0.74, 95% confidence interval (CI): 0.58-0.96), but not for patients with an intermediate PC-CS compared with patients with a poor PC-CS (RR: 0.95, 95% CI: 0.78-1.15). Multivariable analyses showed a statistically significant lower risk of poor outcome for the presence of at least one posterior communicating artery and for larger caliber of posterior communicating arteries (RR: 0.79, 95% CI: 0.66-0.95 and 0.76, 95% CI: 0.61-0.96, respectively). CONCLUSIONS: The PC-CS predicted poor outcome at one month. In a separate analysis, both the absence and smaller caliber of posterior communicating arteries predicted poor outcome.

What is the relationship among penumbra volume, collaterals, and time since onset in the first 6 h after acute ischemic stroke?

BACKGROUND: The steep, time-dependent loss of benefit from reperfusion in clinical trials is consistent with loss of penumbra over the early hours of ischemia, as observed in animal models. Human imaging studies, however, show persistent penumbra for up to 48 h. We investigated core and penumbra volumes and collateral status in relation to time after stroke onset within the first 6 h. METHODS: Using data from three multimodal computer tomography-based studies in acute ischemic stroke patients <6 h after onset, we measured core and penumbra volumes, collateral status, and target mismatch (defined as core volume < 50 ml, perfusion lesion volume > 15 ml, mismatch ratio > 1.8). Patients were grouped by onset to imaging time (<3, 3-4.5, 4.5-6 h). We explored correlates of penumbra proportion by multivariable linear regression. RESULTS: Analysis included 144 subjects. Across time epochs, neither proportions of penumbra (59%, 64%, 75% at <3, 3-4.5, >4. 5 h, respectively, p = 0.4) nor poor collaterals (15/56 (27%), 14/47 (30%), 4/15 (27%) at <3, 3-4.5, >4.5 h, p = 0.9) differed significantly. Penumbra proportion was not clearly related to time to imaging (R(2) = 0.003; p = 0.5) but a trend for divergent effects by collateral status was seen (slight increase in penumbra over time with good collaterals versus reduced with poor, interaction = 0.08). The proportion of patients with target mismatch did not vary by time (56%, 74%, and 67% at <3, 3-4.5, >4.5 h, p = 0.09). CONCLUSIONS: In a cross-sectional sample imaged within 6 h, neither the proportions of penumbral tissue nor "target mismatch" varied by time from onset. A trend for reducing penumbra proportion only among those with poor collaterals may have pathophysiological and therapeutic importance.

How many stroke patients might be eligible for mechanical thrombectomy?

INTRODUCTION: Recent studies showed improved patient outcomes with endovascular treatment of acute stroke compared to medical care, including IV rtPA, alone. Seven trials have reported results, each using different clinical and imaging criteria for patient selection. We compared eligibility for different trial protocols to estimate the number of patients eligible for treatment. PATIENTS AND METHODS: Patient data were extracted from a single centre database that combined patients recruited to three clinical studies, each of which obtained both CTA and CTP within 6 h of stroke onset. The published inclusion and exclusion criteria of seven intervention trials (MR CLEAN, EXTEND-IA, ESCAPE, SWIFT-PRIME, REVASCAT, THERAPY and THRACE) were applied to determine the proportion that would be eligible for each of these studies. RESULTS: A total of 263 patients was included. Eligibility for IAT in individual trials ranged from 53% to 3% of patients; 17% were eligible for four trials and under 10% for two trials. Only three patients (1%) were eligible for all studies. The most common cause of exclusion was absence of large artery occlusion (LAO) on CTA. When applying simplified criteria requiring an ASPECT score > 6, 16% were eligible for IAT, but potentially 40% of these patients were excluded by perfusion criteria and more than half by common NIHSS thresholds. CONCLUSION: Around 15% of patients presenting within 6 h of stroke onset were potentially eligible for IAT, but clinical trial eligibility criteria have much more limited overlap than is commonly assumed and only 1% of patients fulfilled criteria for all recent trials.

Clinical and diagnostic findings in patients with elevated cerebrospinal bilirubin.

INTRODUCTION: Cerebrospinal fluid (CSF) spectroscopy can identify subarachnoid haemorrhage (SAH) when CT is negative in patients presenting with acute severe headache. The primary objective of this study was to evaluate the clinical use and usefulness of CSF spectrophotometry. Secondary objectives were to identify other causes of elevated CSF bilirubin, to analyse headache descriptions and to compare clinical features in patients with an elevated CSF bilirubin among those with and without an intracranial vascular cause of SAH (avSAH). METHODS: Consecutive patients admitted to two hospitals in Enniskillen and Londonderry between 1 January 2004 and 30 September 2014 with CSF spectroscopy bilirubin results were identified from a clinical chemistry laboratory dataset. Patients with elevated CSF bilirubin were studied. Clinical demographics, delays to investigation and final diagnoses were recorded. Patients with avSAH were compared with patients without avSAH. RESULTS: Among 1813 patients with CSF spectrophotometry results, requests increased more than threefold during the study (p<0.001). Fifty-six patients had elevated CSF bilirubin. Ten (17.9%) had avSAH, of which 8 (14.3%) had aneurysmal SAH. Non-vascular causes of elevated CSF bilirubin included meningitis, spontaneous intracranial hypotension and carcinomatous meningitis. Headache descriptions varied. Time from headache onset to admission, CT scan and lumbar puncture did not differ significantly for patients with avSAH and non-avSAH. CSF red cell counts were higher among patients with avSAH than patients with non-avSAH (p=0.005). CONCLUSIONS: CSF bilirubin measurement has an important role in identifying avSAH in CT-negative patients presenting with a thunderclap headache. Better clinical selection of patients is required as CSF spectrophotometry, although sensitive, is not specific for SAH.

Derivation and evaluation of thresholds for core and tissue at risk of infarction using CT perfusion.

BACKGROUND AND PURPOSE: Computed tomography perfusion provides information on tissue viability according to proposed thresholds. We evaluated thresholds for ischemic core and tissue at risk and subsequently tested their accuracy in independent datasets. MATERIALS AND METHODS: Tissue at risk was evaluated in patients with persistent arterial occlusions, and ischemic core thresholds in patients with recanalization and major clinical improvement. Scans were randomly allocated to derivation or validation groups for tissue at risk and core analysis. Optimum thresholds using mean transit time (MTT), cerebral blood flow (CBF), cerebral blood volume, and delay time (DT) were assessed. RESULTS: Absolute MTT, relative MTT and DT were best derived predictors of tissue at risk with thresholds of ≥ 7 seconds, ≥ 125%, and ≥ 2 seconds respectively. DT ≥ 2 seconds was the best predictor in the validation dataset (95% agreement levels = -44 to +30 mL, Bias = -6.9). Absolute and relative MTT were the best derived predictors of infarct volume in the core group (8 seconds and 125% respectively) but relative CBF of ≤ 45% performed best in the core validation dataset. CONCLUSIONS: Time-based perfusion thresholds perform well as predictors of tissue at risk of infarction with DT the best predictor. Relative CBF was the best predictor of ischemic core. Evaluation in larger populations is needed to confirm the performance of tissue viability thresholds.

Clinical relevance and practical implications of trials of perfusion and angiographic imaging in patients with acute ischaemic stroke: a multicentre cohort imaging study.

BACKGROUND: In randomised trials testing treatments for acute ischaemic stroke, imaging markers of tissue reperfusion and arterial recanalisation may provide early response indicators. OBJECTIVE: To determine the predictive value of structural, perfusion and angiographic imaging for early and late clinical outcomes and assess practicalities in three comprehensive stroke centres. METHODS: We recruited patients with potentially disabling stroke in three stroke centres, performed magnetic resonance (MR) or CT, including perfusion and angiography imaging, within 6 h, at 72 h and 1 month after stroke. We assessed the National Institutes of Health Stroke Scale (NIHSS) score serially and functional outcome at 3 months, tested associations between clinical variables and structural imaging, several perfusion parameters and angiography. RESULTS: Among 83 patients, median age 71 (maximum 89), median NIHSS 7 (range 1-30), 38 (46%) received alteplase, 41 (49%) had died or were dependent at 3 months. Most baseline imaging was CT (76%); follow-up was MR (79%) despite both being available acutely. At presentation, perfusion lesion size varied considerably between parameters (p<0.0001); 40 (48%) had arterial occlusion. Arterial occlusion and baseline perfusion lesion extent were both associated with baseline NIHSS (p<0.0001). Recanalisation by 72 h was associated with 1 month NIHSS (p=0.0007) and 3 month functional outcome (p=0.048), whereas tissue reperfusion, using even the best perfusion parameter, was not (p=0.11, p=0.08, respectively). CONCLUSION: Early recanalisation on angiography appeared to predict clinical outcome more directly than did tissue reperfusion. Acute assessment with CT and follow-up with MR was practical and feasible, did not preclude image analysis, and would enhance trial recruitment and generalisability of results.

Iodinated contrast media and cerebral hemorrhage after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Iodinated contrast is increasingly used in CT perfusion or angiographic examinations in acute stroke. Increased risk of intracranial hemorrhage (ICH) complicating microcatheter contrast injections has recently been reported in the second Interventional Management of Stroke (IMS 2) trial with contrast toxicity potentially contributory. METHODS: We reviewed clinical and radiological data on all patients treated with intravenous alteplase at a single center between May 2003 and November 2008. RESULTS: Of 312 patients treated with intravenous alteplase, 69 (22.1%) received intravenous iodinated contrast in volumes between 50 and 150 mL. Incidence of symptomatic ICH defined as per European Cooperative Acute Stroke Study 2 was 16 of 312 (5.1%; 95% CI, 2.7% to 7.6%); among patients not given contrast, it was 12 of 243 (4.9%; 2.2% to 7.7%) compared with 4 of 69 (5.8%; 0.3% to 11.3%) in those given contrast. Incidence of symptomatic ICH defined as per Safe Implementation of Thrombolysis in Stroke-MOnitoring Study (SITS-MOST) criteria was 12 of 312 (3.9%; 1.7% to 6%), 9 of 243 (3.7%; 1.3% to 6%) among those not given contrast, and 3 of 69 (4.4%; 95% CI, -0.5% to 9.2%) among those given contrast. Patients with symptomatic ICH were older, had higher pretreatment National Institutes of Health Stroke Scale, and blood glucose than those without symptomatic ICH. In logistic regression analysis, pretreatment blood glucose was the only significant predictor of symptomatic ICH by either definition (OR, 1.23; 95% CI, 1.03 to 1.48 per mmol/L increment; P=0.024). Contrast administration or dose was not associated with symptomatic ICH. CONCLUSIONS: Intravenous iodinated contrast in doses typically required for CT angiography and perfusion imaging was not associated with symptomatic intracranial hemorrhage in patients treated with alteplase.