Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial.

BACKGROUND: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days. METHODS: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient (r) with 95% CI. RESULTS: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase (P=0.10). Older age (P<0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale (P<0.01), and longer stroke onset-to-needle time (P=0.004) were associated with lower EQ5D index and VAS scores. There was a strong association (r, 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index (r, 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores (r, 0.42 [95% CI, 0.37-0.46]). CONCLUSIONS: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Pearls & Oy-sters: Trigeminal Cystic Schwannoma Presenting With Foster Kennedy Syndrome, Sixth Nerve Palsy, and Focal Seizures.

Foster Kennedy syndrome refers to a finding of optic atrophy in one eye from direct compression of the optic nerve by a mass lesion and contralateral papilledema in the nonatrophic optic nerve caused by an increased intracranial pressure. When the fundoscopy finding is not due to a direct compressive mass, the term pseudo-Foster Kennedy syndrome is used; this can be caused by any process or processes that result in optic atrophy in one eye and optic disc edema in the other. Identifying Foster Kennedy syndrome in a patient calls for expedient neuroimaging looking for an intracranial mass lesion. In this article, we present the case of a patient presenting with vision loss and Foster Kennedy syndrome who was found to have a large trigeminal cystic schwannoma. While several other accompanying symptoms were not evident from the patient complaint, a careful history and physical examination revealed additional localizing clues: unilateral sensory changes in the face and pterygoid and masseter atrophy, unilateral cranial nerve VI palsy, and episodes of intense déjà vu sensation, which were presumed to represent temporal lobe-onset focal aware seizures. Trigeminal schwannomas are a rare entity, and they are even more rarely cystic. This case highlights an unusual scenario where a slow expansion of the tumor ultimately resulted in vision loss and presentation of the patient to medical attention.

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial.

BACKGROUND: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care. METHODS: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual. FINDINGS: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis. FUNDING: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

On the Value of Information in Status Update Systems.

The age of information (AoI) is now well established as a metric that measures the freshness of information delivered to a receiver from a source that generates status updates. This paper is motivated by the inherent value of packets arising in many cyber-physical applications (e.g., due to precision of the information content or an alarm message). In contrast to AoI, which considers all packets are of equal importance or value, we consider status update systems with update packets carrying values as well as their generated time stamps. A status update packet has a random initial value at the source and a deterministic deadline after which its value vanishes (called ultimate staleness). In our model, the value of a packet either remains constant until the deadline or decreases in time (even after reception) starting from its generation to the deadline when it vanishes. We consider two metrics for the value of information (VoI) at the receiver: sum VoI is the sum of the current values of all packets held by the receiver, whereas packet VoI is the value of a packet at the instant it is delivered to the receiver. We investigate various queuing disciplines under potential dependence between value and service time and provide closed form expressions for both average sum VoI and packet VoI at the receiver. Numerical results illustrate the average VoI for different scenarios and relations between average sum VoI and average packet VoI.

A Rare Ocular Manifestation of Idiopathic Hypertrophic Cranial Pachymeningitis.

Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare form of thickening of the dura mater. There are limited reports on the ocular manifestation of IHCP and its treatment. Up to our knowledge, there is no report on bilateral superior ophthalmic veins (SOV) dilatation with IHCP and there are only a few reports on anterior scleritis with IHCP. We report a 62-year-old gentleman with underlying hypertension and chronic headache who presented with fever, headache, and unresolving both eyes redness as manifestations of bilateral anterior scleritis, anterior uveitis, secondary glaucoma, and multiple cranial nerve palsies. Magnetic resonance imaging of the brain showed global thickening and enhancement of the pachymeninges with bilateral SOV dilatations. The diagnosis of IHCP was made after ruling out infective and autoimmune causes. The patient was treated with oral prednisolone, oral azathioprine, topical timolol maleate, topical dexamethasone, and topical moxifloxacin. The patient was successfully treated and was stable throughout two years review. In conclusion, unresolved red eyes with headaches can be an early presentation of IHCP. Pathophysiology and treatment of the ocular manifestations and IHCP were discussed.

Cytomegalovirus retinitis associated with high CD4 counts and DHEA abuse.

The most frequent ocular manifestation of acquired immunodeficiency syndrome (AIDS) is cytomegalovirus retinitis (CMVR). This infection is reportedly inversely proportional to the CD4 counts. Usually CMVR develops once the CD4 counts fall below 50/mm3. Our case report documents an AIDS patient who developed CMVR despite CD4 counts being persistently >200/mm3. The patient was self-administering dehydroepiandrosterone, high dose Vitamin C, testosterone and hydrocortisone. This case report describes a unique case of pharmacologically induced elevated CD4 counts, which however, did not prevent the development of CMVR in the patient.

Three dimensional neuro-retinal rim thickness and retinal nerve fiber layer thickness using high-definition optical coherence tomography for open-angle glaucoma.

PURPOSE: To compare the diagnostic capability of three-dimensional (3D) neuro-retinal rim thickness (NRR) with existing optic nerve head and retinal nerve fiber layer (RNFL) scan parameters using high-definition optical coherence tomography (HD-OCT). DESIGN: Retrospective study. METHODS: Based on the mean deviation (MD) of the Humphrey Field Analyzer (HFA), the 152 subjects were categorized into mild (MD > - 6 dB, 100), moderate (MD - 6 to - 12 dB, 26), and severe (MD < - 12 dB, 26) glaucoma. The HD-OCT values of NRR, RNFL and ganglion cell inner plexiform layer (GCIPL) thicknesses, along with those of other parameters (rim area, disc area) were obtained, and the average NRR thickness was calculated. RESULTS: For all of the HD-OCT parameters, RNFL thickness showed a higher area under the ROC (AUROC) curve (range: 0.937-1.000) than did NRR thickness (range: 0.827-1.000). There were significant RNFL, NRR, and GCIPL AUROC curve differences among the mild, moderate and severe glaucoma groups. RNFL thickness for mild glaucoma showed a significantly larger area than did NRR thickness [area difference: 0.110 (± 0.025); p value < 0.0001). Furthermore, RNFL relative to NRR thickness yielded higher sensitivity (85-100% vs. 72-100%) and specificity (89-100% vs. 84-100%) for diagnosis of glaucoma. CONCLUSION: RNFL thickness remains significantly better than 3D NRR thickness in terms of glaucoma-diagnostic capability in HD-OCT.

Compact OXC architecture, design and prototype development for flexible waveband routing optical networks.

A novel compact OXC node architecture that combines WSSs and arrays of small scale optical delivery-coupling type switches ("DCSWs") is proposed. Unlike conventional OXC nodes, the WSSs are only responsible for dynamic path bundling ("flexible waveband") while the small scale optical switches route bundled path groups. A network design algorithm that is aware of the routing scheme is also proposed, and numerical experiments elucidate that the necessary number of WSSs and amplifiers can be significantly reduced. A prototype of the proposed OXC is also developed using monolithic arrayed DCSWs. Transmission experiments on the prototype verify the proposal's technical feasibility.

Obesity and Weight Loss in Idiopathic Intracranial Hypertension: A Narrative Review.

BACKGROUND: Most patients with idiopathic intracranial hypertension (IIH) are obese. Weight loss is felt to be an important factor in improving IIH. The mechanism by which weight loss leads to a reduction in elevated intracranial pressure is unclear. Evidence from prospective studies evaluating the role of weight loss in IIH is lacking. EVIDENCE ACQUISITION: We performed a detailed review of the published literature regarding the association of IIH and obesity, including proposed pathogenetic mechanisms, and the effect of weight loss and weight-loss interventions in IIH. References were identified by searching PubMed with the terms idiopathic intracranial hypertension and weight loss. Additional citations were found in the identified references. RESULTS: Over 90% of IIH patients are obese or overweight. The risk of IIH increases as a function of body mass index (BMI) and weight gain over the preceding year. The risk of IIH-induced vision loss also increases with increasing BMI, especially with BMI >40 kg/m. Several mechanisms have been proposed linking obesity to the development of IIH but the pathophysiology remains unknown. Published studies and clinical observations strongly support weight loss as an effective treatment, although there are no prospective controlled trials. Weight loss in the range of 6%-10% often leads to IIH remission. Weight loss of ≥5% at 1 year is achieved in roughly 50%-70% of patients if they are enrolled in a high-intensity lifestyle modification program and in 20%-35% of patients if they direct their own weight loss. Weight is typically regained over 1-3 years but about a third of patients maintain ≥5% weight loss over the long term. Patients treated initially with lifestyle modification therapy show a modest persisting benefit over self-directed patients. Selected commercial weight loss programs also may improve long-term maintenance of weight loss. New antiobesity drugs significantly improve the proportion of obese patients who have ≥5% loss of weight at 1 year. CONCLUSIONS: Obesity is an important contributing factor for the development of IIH, although the pathophysiological mechanism linking obesity to IIH is unknown. The risk of developing IIH and associated visual loss increases with increasing BMI. Weight loss is an effective treatment for IIH. Long-term maintenance of initial weight loss is helped modestly by lifestyle modification programs and possibly by selected commercial weight loss programs. New antiobesity drugs may provide further options for IIH therapy in the future.

Effective signaling of surface boundaries by L-vertices reflect the consistency of their contrast in natural images.

An L-vertex, the point at which two contours coterminate, provides highly reliable evidence that a surface terminates at that vertex, thus providing the strongest constraint on the extraction of shape from images (Guzman, 1968). Such vertices are pervasive in our visual world but the importance of a statistical regularity about them has been underappreciated: The contours defining the vertex are (almost) always of the same direction of contrast with respect to the background (i.e., both darker or both lighter). Here we show that when the two contours are of different directions of contrast, the capacity of the L-vertex to signal the termination of a surface, as reflected in object recognition, is markedly reduced. Although image statistics have been implicated in determining the connectivity in the earliest cortical visual stage (V1) and in grouping during visual search, this finding provides evidence that such statistics are involved in later stages where object representations are derived from two-dimensional images.

Magnitude of Hematoma Volume Measurement Error in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Limiting intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) expansion is a common target for acute ICH studies and, therefore, accurate measurement of hematoma volumes is required. We investigated the amount of hematoma volume difference between computed tomography scans that can be considered as measurement error. METHODS: Five raters performed baseline (<6 hours) and 24-hour total hematoma (ICH+IVH) computer-assisted volumetric analysis from 40 selected ICH patients from the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study cohort twice. Estimates of intrarater and interrater reliability are expressed as intraclass correlation coefficients and minimum detectable difference (MDD). RESULTS: Total hematoma volumetric analyses had excellent intra- and interrater agreements (intraclass correlation coefficients 0.994 and 0.992, respectively). MDD for intra- and interrater volumes was 6.68 and 7.72 mL, respectively, and were higher the larger total hematoma volume was and in patients with subarachnoid hemorrhage or IVH. MDD for total hematoma volume measurement of 10.4 mL was found in patients with largest hematoma volumes. In patients with subarachnoid hemorrhage or IVH, MDD for total hematoma volume was 10.3 and 10.4 mL, respectively. In patients without IVH, MDD for intra- and interrater pure ICH volumes were 3.82 and 5.83 mL, respectively. CONCLUSIONS: A threshold higher than 10.4 mL seems to be reliable to avoid error of total hematoma volume measurement in a broad range of patients. An absolute ICH volume increase of >6 mL, commonly used as outcome in ICH studies, seems well above MDD and, therefore, could be used to reliably detect ICH expansion.

Perihematomal Edema Is Greater in the Presence of a Spot Sign but Does Not Predict Intracerebral Hematoma Expansion.

BACKGROUND AND PURPOSE: Perihematomal edema volume may be related to intracerebral hemorrhage (ICH) volume at baseline and, consequently, with hematoma expansion. However, the relationship between perihematomal edema and hematoma expansion has not been well established. We aimed to investigate the relationship among baseline perihematomal edema, the computed tomographic angiography spot sign, hematoma expansion, and clinical outcome in patients with acute ICH. METHODS: Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) was a prospective observational cohort study of ICH patients presenting within 6 hours from onset. Patients underwent computed tomography and computed tomographic angiography scans at baseline and 24-hour computed tomography scan. A post hoc analysis of absolute perihematomal edema and relative perihematomal edema (absolute perihematomal edema divided by ICH) volumes was performed on baseline computed tomography scans (n=353). Primary outcome was significant hematoma expansion (>6 mL or >33%). Secondary outcomes were early neurological deterioration, 90-day mortality, and poor outcome. RESULTS: Absolute perihematomal edema volume was higher in spot sign patients (24.5 [11.5-41.8] versus 12.6 [6.9-22] mL; P<0.001), but it was strongly correlated with ICH volume (ρ=0.905; P<0.001). Patients who experienced significant hematoma expansion had higher absolute perihematomal edema volume (18.4 [10-34.6] versus 11.8 [6.5-22] mL; P<0.001) but similar relative perihematomal edema volume (1.09 [0.89-1.37] versus 1.12 [0.88-1.54]; P=0.400). Absolute perihematomal edema volume and poorer outcomes were higher by tertiles of ICH volume, and perihematomal edema volume did not independently predict significant hematoma expansion. CONCLUSIONS: Perihematomal edema volume is greater at baseline in the presence of a spot sign. However, it is strongly correlated with ICH volume and does not independently predict hematoma expansion.

Randomized assessment of rapid endovascular treatment of ischemic stroke.

BACKGROUND: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. METHODS: We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). RESULTS: The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P=0.75). CONCLUSIONS: Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.).

Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion.

BACKGROUND AND PURPOSE: Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK-tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population. METHODS: TNK-Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK-tissue-type plasminogen activator dose-escalation, safety, and feasibility trial. Patients with a National Institutes of Health Stroke Scale ≤5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible. Fifty patients were enrolled; 25 patients at a dose of 0.1 mg/kg, and 25 patients at 0.25 mg/kg. Primary outcome was the rate of drug-related serious adverse events. Secondary outcomes included recanalization and 90-day neurological outcome (modified Rankin Scale, 0-1). RESULTS: Median baseline National Institutes of Health Stroke Scale was 2.5 (interquartile range, 1), and median age was 71 (interquartile range, 22) years. There were no drug-related serious adverse events in tier 1. In tier 2, there was 1 symptomatic intracranial hemorrhage (4%; 95% confidence interval, 0.01-20.0). Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome (modified Rankin Scale, 0-1) at 90 days. Recanalization rates were high; 0.1 mg/kg (39% complete and 17% partial), 0.25 mg/kg (52% complete and 9% partial). Complete recanalization was significantly related to excellent functional outcome (modified Rankin Scale, 0-1) at 90 days (relative risk, 1.65; 95% confidence interval, 1.09-2.5; P=0.026). CONCLUSIONS: Administration of TNK-tissue-type plasminogen activator in minor stroke with intracranial occlusion is both feasible and safe. A larger randomized controlled trial is needed to prove that this treatment is efficacious. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654445.

Baroreflex failure, sympathetic storm, and cerebral vasospasm in fibulin-4 cutis laxa.

Sudden, severe, and life-threatening, the crises associated with baroreflex failure are diagnostically challenging, particularly in children, a population in which it has rarely been described. The baroreflex failure syndrome results from impaired afferent baroreceptive input and manifests with autonomic stimulation-induced surges in blood pressure and heart rate accompanied by distinct signs, including thunderclap headache, diaphoresis, and emotional instability. Although the adult literature includes cases of severe headache in baroreflex failure,(1) (,) (2) we present the first case of a child with recurrent thunderclap headache and cerebral vasospasm with baroreflex failure secondary to vascular complications of a rare genetic connective tissue disorder.

Planimetric hematoma measurement in patients with intraventricular hemorrhage: is total volume a preferred target for reliable analysis?

BACKGROUND AND PURPOSE: Reliable quantification of both intracerebral hemorrhage and intraventricular hemorrhage (IVH) volume is important for hemostatic trials. We evaluated the reliability of computer-assisted planimetric volume measurements of IVH. METHODS: Computer-assisted planimetry was used to quantify IVH volume. Five raters measured IVH volumes, total (intracerebral hemorrhage+IVH) volumes, and Graeb scores from 20 randomly selected computed tomography scans twice. Estimates of interrater and intrarater reliability were calculated and expressed as an intrarater correlation coefficient and an absolute minimum detectable difference. RESULTS: Planimetric IVH volume analysis had excellent intra- and interrater agreement (intrarater correlation coefficient, 0.96 and 0.92, respectively), which was superior to the Graeb score (intrarater correlation coefficient, 0.88 and 0.83). Minimum detectable differences for intra- and interrater volumes were 12.1 mL and 17.3 mL, and were dependent on the total size of the hematoma; hematomas smaller than the median 43.8 mL had lower minimum detectable differences, whereas those larger than the median had higher minimum detectable differences. Planimetric total hemorrhage volume analysis had the best intra- and interrater agreement (intrarater correlation coefficient, 0.99 and 0.97, respectively). CONCLUSIONS: Computer-assisted planimetric techniques provide a reliable measurement of ventricular hematoma volume, but are susceptible to higher absolute error when assessing larger hematomas.

Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study.

BACKGROUND: In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion. METHODS: PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis. FINDINGS: We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22-470), and time from onset to CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5-80·9) in spot-sign-positive patients versus 10·0 mL (0·1-102·7) in spot-sign negative patients (p<0·001). Median ICH expansion was 8·6 mL (-9·3 to 121·7) for spot-sign positive patients and 0·4 mL (-11·7 to 98·3) for spot-negative patients (p<0·001). In those with haematoma expansion, the positive predictive value for the spot sign was61% (95% CI 47­73) for the positive predictive value and 78% (71­84) for the negative predictive value, with 51% (39­63) sensitivity and 85% (78­90) specificity[corrected]. Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p<0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4-4·0, p=0·002). INTERPRETATION: These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH. FUNDING: Canadian Stroke Consortium and NovoNordisk Canada.