Endovascular treatment beyond 24 hours from the onset of acute ischemic stroke: the Italian Registry of Endovascular Thrombectomy in Acute Stroke (IRETAS)

BackgroundClinical trials and observational studies have demonstrated the benefit of thrombectomy up to 16 or 24 hours after the patient was last known to be well. This study aimed to evaluate the outcome of stroke patients treated beyond 24 hours from onset.MethodsWe analyzed the outcome of 34 stroke patients (mean age 70.7±12.3 years; median National Institutes of Health Stroke Scale (NIHSS) score 13) treated with endovascular thrombectomy beyond 24 hours from onset who were recruited in the Italian Registry of Endovascular Thrombectomy in Acute Stroke. Selection criteria for patients were: pre-stroke modified Rankin scale (mRS) score of ≤2, non-contrast CT Alberta Stroke Program Early CT score of ≥6, good collaterals on single phase CT angiography (CTA) or multiphase CTA, and CT perfusion mismatch with an infarct core size ≤50% of the total hypoperfusion extent or involving less than one-third of the extent of the middle cerebral artery territory evaluated by visual inspection. The primary outcome measure was functional independence assessed by the mRS at 90 days after onset. Safety outcomes were 90 day mortality and the occurrence of symptomatic intracranial hemorrhage (sICH).ResultsSuccessful recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was present in 76.5% of patients. Three month functional independence (mRS score 0–2) was observed in 41.1% of patients. The case fatality rate was 26.5%. and the incidence of sICH was 8.8%.ConclusionsThese findings suggest that, in a real world setting, very late endovascular therapy is feasible in appropriately selected patients.

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Abstract WP83: Validation of a Relative Non-Contrast CT Map to Detect Early Ischemic Changes in Acute Stroke

Stroke ◽

10.1161/str.51.suppl_1.wp83 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Margy E McCullough-Hicks ◽

Soren Christensen ◽

Aditya Srivatsan ◽

Gregory W Albers ◽

Maarten Lansberg

Keyword(s):

Acute Stroke ◽

Brain Regions ◽

Lesion Volume ◽

Stroke Patients ◽

Infarct Core ◽

Test Characteristics ◽

Contrast Ct ◽

Sensitivity Specificity ◽

Early Infarction

Background: Discerning signs of early infarct on the non-contrast CT (NCCT) can be difficult. To facilitate interpretation of the NCCT we previously developed a technique to generate symmetry ratio maps of the NCCT (rNCCT maps) on which subtle (≥5%) differences in density between symmetric brain regions are enhanced. We sought to validate the rNCCT map against other measures of early infarction in a large cohort. Methods: rNCCT maps were generated for 146 ischemic stroke patients. We assessed how often a neurologist’s interpretation of the NCCT was changed when provided with the rNCCT map. The neurologist was blinded to CTP and DWI but was given the infarct hemisphere. In addition, using the 24-hour DWI as the gold standard, we assessed the sensitivity, specificity and volumetric accuracy of the rNCCT-defined infarct core and compared this to the test characteristics of CTP-defined infarct core (CBF<38% threshold). Results: Addition of rNCCT overlay map changed clinician’s initial read 64.4% of the time (95% CI 56-72%); the rNCCT identified new areas of ischemia not appreciated on blinded review 86.2% of the time (95% CI 78-92%) and in 35.1% helped rule out early ischemia where the reader was unsure of its presence (95% CI 26-45%). In the 53 patients with reperfusion and follow-up MRI, specificity of rNCCT for final lesion volume was 99.5% for rNCCT [98.5-99.8%] vs. 99.8% [IQR 98.8-99.9%] for CTP (P=0.08). Sensitivity for rNCCT was 19.9% [7.1-28.1%] vs. 17.5% [4.7-32.2%] for CTP (P=0.56). Conclusions: This study validates the rNCCT map for detection of early ischemic changes. It is more quantitative and objective than a clinician’s read of the NCCT alone. The sensitivity and specificity for detecting early ischemic changes on rNCCT were comparable to those achieved with CTP. This indicates that the rNCCT could be a valuable tool in the evaluation of acute stroke patients.

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Abstract 2697: Fully-automated Identification of Acute Stroke Lesion Volumes with CT Perfusion

Stroke ◽

10.1161/str.43.suppl_1.a2697 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Matus Straka ◽

Gregory W Albers ◽

Maarten G Lansberg ◽

Stephanie M Kemp ◽

Michael P Marks ◽

...

Keyword(s):

Acute Stroke ◽

Ct Perfusion ◽

Automated Image Analysis ◽

Great Promise ◽

Lesion Volume ◽

Stroke Patients ◽

Infarct Core ◽

Median Volume ◽

Stroke Lesion ◽

Volume Difference

Purpose: Mismatch between volumes of infarct core and critically hypoperfused tissue (CHT) may be used to identify acute stroke patients who could benefit from reperfusion therapies. We present a fully-automated, operator-free approach for identifying the core and CHT lesion volumes with CT perfusion (CTP). Methods: 31 scans of 25 acute stroke patients who underwent CTP followed by MRI (range: 23-120 min) were analyzed. CTP was obtained as a one or two 2cm slabs. MRI included DWI and PWI. Reference stroke lesion metrics were MRI-based: core via DWI (ADC<615x10 -6 mm 2 /s), and CHT via PWI (Tmax>6s). CTP and PWI scans were processed with an automated image analysis program (RAPID) with delay-independent deconvolution. MRI maps were coregistered to CTP. Contralaterally-relative CBV CT and CBF CT ( cr CBF CT , cr CBF CT ) maps were computed by putting into ratio the original and corresponding laterally-mirrored and smoothed rCBV CT and rCBF CT maps (obtained by vertical flip and coregistration of the anatomic images, see Fig). Stroke core in CTP was delineated by thresholding cr CBV CT and cr CBF CT , and CHT by thresholding Tmax CT . Optimal thresholds were obtained by ROC analysis and minimization of lesion volume differences between CT and MRI. Results: For identification of stroke core in CTP, cr CBF CT performed better than cr CBV CT . Optimal threshold was cr CBF CT < 0.30 with sensitivity 60% (CI 95% 57-63%) and specificity 88%, (CI 95% 87-89%); median volume difference between CBF CT and DWI lesions was 0 ml (IQR: -6ml to 6 ml); correlation of volumes was r 2 =0.72 ( p <0.0001). For identification of CHT, reference MRI lesions (Tmax MR >6s) were most accurately identified by Tmax CT >6s with sensitivity 72% (CI 95% 70-74%), specificity 97% (CI 95% 96-97%); median volume difference between Tmax CT and Tmax MR was -3ml (IQR: -10ml to 0ml); correlation of CHT volumes r 2 =0.89 (p<0.0001). Conclusions: The processing methods and CTP thresholds presented in this study show a great promise for fully-automated outlining of stroke lesions using CTP. Such a technique could be of great value for CTP-based patient selection in clinical trials and clinical practice.

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Admission CT perfusion may overestimate initial infarct core: the ghost infarct core concept

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2016-012494 ◽

2016 ◽

Vol 9 (1) ◽

pp. 66-69 ◽

Cited By ~ 33

Author(s):

Sandra Boned ◽

Marina Padroni ◽

Marta Rubiera ◽

Alejandro Tomasello ◽

Pilar Coscojuela ◽

...

Keyword(s):

Cerebral Blood Volume ◽

Time Window ◽

Ct Perfusion ◽

Early Time ◽

Infarct Core ◽

Vessel Occlusion ◽

Endovascular Thrombectomy ◽

Adjusted Logistic Regression ◽

Contrast Ct

BackgroundIdentifying infarct core on admission is essential to establish the amount of salvageable tissue and indicate reperfusion therapies. Infarct core is established on CT perfusion (CTP) as the severely hypoperfused area, however the correlation between hypoperfusion and infarct core may be time-dependent as it is not a direct indicator of tissue damage. This study aims to characterize those cases in which the admission core lesion on CTP does not reflect an infarct on follow-up imaging.MethodsWe studied patients with cerebral large vessel occlusion who underwent CTP on admission but received endovascular thrombectomy based on a non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS) >6. Admission infarct core was measured on initial cerebral blood volume (CBV) CTP and final infarct on follow-up CT. We defined ghost infarct core (GIC) as initial core minus final infarct >10 mL.Results79 patients were studied. Median National Institutes of Health Stroke Scale (NIHSS) score was 17 (11–20), median time from symptoms to CTP was 215 (87–327) min, and recanalization rate (TICI 2b–3) was 77%. Thirty patients (38%) presented with a GIC >10 mL. GIC >10 mL was associated with recanalization (TICI 2b–3: 90% vs 68%; p=0.026), admission glycemia (<185 mg/dL: 42% vs 0%; p=0.028), and time to CTP (<185 min: 51% vs >185 min: 26%; p=0.033). An adjusted logistic regression model identified time from symptom to CTP imaging <185 min as the only predictor of GIC >10 mL (OR 2.89, 95% CI 1.04 to 8.09). At 24 hours, clinical improvement was more frequent in patients with GIC >10 mL (66.6% vs 39%; p=0.017).ConclusionsCT perfusion may overestimate final infarct core, especially in the early time window. Selecting patients for reperfusion therapies based on the CTP mismatch concept may deny treatment to patients who might still benefit from reperfusion.

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Abstract WP471: Significant Factors for Early Independent Toilet Activities in Acute Stroke Patients

Stroke ◽

10.1161/str.51.suppl_1.wp471 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Yuki Sawada ◽

Takahisa Mori ◽

Yuna Hosaka

Keyword(s):

Cognitive Function ◽

Acute Stroke ◽

Mmse Score ◽

Multiple Logistic Regression Analysis ◽

Early Discharge ◽

Functional Independence ◽

Lower Limbs ◽

Stroke Patients ◽

Trunk Control ◽

Significant Factors

Introduction: Acute stroke patients have problems with toilet activities. Independent toilet activity in hospitalized patients is important for dischargee to home. Hypothesis: Lower limbs function, trunk control and cognitive function are important factors of early independent toilet activities and discharge to home within 7 days. Methods: We included acute ischemic stroke patients who 1) were admitted from June 2017 to May 2018 and 2) received early rehabilitation treatment. Patients with disturbed level of consciousness were excluded. Functional independence measure (FIM) scale of 6 or 7 was defined as independence and FIM scale of 5 or less as dependence. We evaluated Brunnstrom Recovery Stage (BRS) of arms, fingers and lower limbs, trunk control test (TCT), Mini-Mental State Examination (MMSE) and investigated significant factors of early independent toilet activities and discharge to home within 7 days. Results: One-hundred twenty-four patients met our inclusive criteria. Their average age was 75.8 years, male gender of 63.7%, median BRS of arms, fingers and lower limbs was 5, 5 and 5, median TCT score and MMSE score were 94 and 24.7, respectively. Fifty-three patients were independent in toilet activity and 73 patients were dependent. All patients with independent toilet activity discharged to home within 7 days. In independent and dependent toilet activity patients, an average age was 73.6 and 77.4 (p<0.05), median BRS of arms was 5 and 5 (p<0.01), median BRS of fingers was 6and 5 (p<0.01), median BRS of lower limbs was 5 and 5 (p<0.01), median TCT score was 100 and 61 (p<0.01), and median MMSE score was 27.8 and 22.5 (p<0.01), respectively. Multiple logistic regression analysis showed that MMSE score (p<0.01), TCT score (p<0.01), and BRS of lower limbs (p<0.05) were independent factors for independent toilet activity and discharge to home. Receiver operating characteristic (ROC) curve for early discharge to home demonstrated that cut-off values of MMSE score, TCT score and MRS of lower limbs were 27 or more, 87 or more and 5 or more, respectively. Conclusion: BRS as lower limbs function, TCT as trunk control and MMSE as cognitive function were important factors of early independent toilet activities and early discharge to home.

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Adherence to Post-Acute Rehabilitation Guidelines Improves Functional Recovery in Stroke

Stroke ◽

10.1161/str.32.suppl_1.333-c ◽

2001 ◽

Vol 32 (suppl_1) ◽

pp. 333-333

Author(s):

Pamela W Duncan ◽

Ronnie D Horner ◽

Dean M Reker ◽

VA Medical Ctr ◽

Kansas City ◽

...

Keyword(s):

Quality Of Care ◽

Acute Stroke ◽

Functional Recovery ◽

Stroke Rehabilitation ◽

Functional Independence ◽

Case Mix ◽

Stroke Patients ◽

Sf 36 ◽

Acute Rehabilitation

97 Purpose & Methods: To assess if compliance with post-stroke rehabilitation guidelines improves functional recovery. The design of the study was an inception cohort of stroke patients followed prospectively for 6 months. The setting was eleven Department of Veteran Affairs Medical Centers providing care to stroke patients. The subjects included 288 selected patients with stroke admitted between January 1998 - March 1999. Data were abstracted from medical records and telephone interviews. Primary outcome was the Functional Independence Motor Score (FIM). Secondary outcomes included Instrumental Activities of Daily Living (IADL), SF-36 physical functioning, and the Stroke Impact Scale (SIS). Acute and post-acute rehabilitation composite compliance scores (range 0–100) were derived from an algorithm. All outcomes were adjusted for case mix. Results: Average compliance scores in acute and post acute care settings were 68.2% (+ 14) and 69.5% (+ 14.4), respectively. After case-mix adjustment, level of compliance with post-acute rehabilitation guidelines was significantly associated with FIM motor, IADL, and the SIS physical domain scores. SF-36 physical function scores and mortality were not affected by compliance with post-acute rehabilitation guidelines. Level of compliance with rehabilitation guidelines in acute settings was unrelated to any of the outcome measures. Conclusion: Process of care in post-acute stroke rehabilitation affects 6-month functional recovery. Our findings support the use of guidelines as means of assessing quality of care and improving outcomes. These quality indicators are needed to ensure that quality of care is not comprised with new organizational and funding changes involving post-acute stroke care.

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Incorporation of relative cerebral blood flow into CT perfusion maps reduces false ’at risk' penumbra

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2017-013268 ◽

2017 ◽

Vol 10 (7) ◽

pp. 657-662 ◽

Cited By ~ 2

Author(s):

Shlomi Peretz ◽

David Orion ◽

David Last ◽

Yael Mardor ◽

Yotam Kimmel ◽

...

Keyword(s):

At Risk ◽

Acute Stroke ◽

Ct Perfusion ◽

False Negative ◽

Stroke Patients ◽

True Negative ◽

True Negative Rate ◽

Negative Rate ◽

Perfusion Maps

PurposeThe region defined as ‘at risk’ penumbra by current CT perfusion (CTP) maps is largely overestimated. We aimed to quantitate the portion of true ‘at risk’ tissue within CTP penumbra and to determine the parameter and threshold that would optimally distinguish it from false ‘at risk’ tissue, that is, benign oligaemia.MethodsAmong acute stroke patients evaluated by multimodal CT (NCCT/CTA/CTP) we identified those that had not undergone endovascular/thrombolytic treatment and had follow-up NCCT. Maps of absolute and relative CBF, CBV, MTT, TTP and Tmax as well as summary maps depicting infarcted and penumbral regions were generated using the Intellispace Portal (Philips Healthcare, Best, Netherlands). Follow-up CT was automatically co-registered to the CTP scan and the final infarct region was manually outlined. Perfusion parameters were systematically analysed – the parameter that resulted in the highest true-negative-rate (ie, proportion of benign oligaemia correctly identified) at a fixed, clinically relevant false-negative-rate (ie, proportion of ‘missed’ infarct) of 15%, was chosen as optimal. It was then re-applied to the CTP data to produce corrected perfusion maps.ResultsForty seven acute stroke patients met selection criteria. Average portion of infarcted tissue within CTP penumbra was 15%±2.2%. Relative CBF at a threshold of 0.65 yielded the highest average true-negative-rate (48%), enabling reduction of the false ‘at risk’ penumbral region by ~half.ConclusionsApplying a relative CBF threshold on relative MTT-based CTP maps can significantly reduce false ‘at risk’ penumbra. This step may help to avoid unnecessary endovascular interventions.

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Abstract P355: Real-Word Performance of Two Automated Software Platforms for Identification of Salvageable Tissue in Stroke Patients: A Single Center Experience

Stroke ◽

10.1161/str.52.suppl_1.p355 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Angelos Katramados ◽

Horia Marin ◽

Maximilian Kole ◽

Owais Alsrouji ◽

Pala Varun ◽

...

Keyword(s):

Ct Perfusion ◽

Stroke Patients ◽

Vessel Occlusion ◽

Significant Discrepancy ◽

Endovascular Thrombectomy ◽

Stroke Treatment ◽

Software Platforms ◽

Automated Software ◽

Selection Of Patients ◽

Selection Of

Background and purpose: Modern stroke treatment has been revolutionized by image-guided selection of patients for endovascular thrombectomy. Current automated platforms allow for real-time identification of large vessel occlusion and salvageable brain tissue. We sought to evaluate the performance of these platforms with regard to identification of infarcted and salvageable tissue. Methods: We studied all patients that presented to Henry Ford Health System hospitals over a period of 6 weeks, received CT perfusion imaging of the brain upon initial presentation. The images were processed with two automated software platforms. We prospectively measured volumes of tissue with cerebral blood flow (CBF) < 30% of contralateral hemisphere, Tmax >6 secs, and hypoperfusion indices (defined as the ratio of volumes Tmax>10 secs and Tmax>6 secs). We compared the outputs of the two platforms and analyzed the performance of each platform. Results: 66 scans were included in our study. Both platforms were able to image all stroke patients within their FDA-approved indications. With regard to all scans, both platforms were noted to demonstrate comparable CBF<30% volumes (6.32 ml. vs 4.97 ml, p=0.276), and hypoperfusion indices (0.278 vs 0.338, p=0.344). However, there was statistically significant discrepancy in the volumes of tissue with Tmax>6 secs (23.96 vs 14.18 ml, p=0.023). Analysis of a subset of 12 scans, with evidence of LVO or severe symptomatic stenosis on corresponding CTA, showed again comparable CBF<30% volumes (12.84 ml vs 13.67 ml, p=0.725), and hypoperfusion indices (0.344 vs 0.314, p=0.699). However, the Tmax>6 secs volume discrepancy was greater and still statistically significant (75.54 ml vs 39.58 ml, p=0.048) Conclusions: Automated software platforms are an invaluable aid in the identification of salvageable tissue, and selection of patients for endovascular thrombectomy in the 6-24 hour window. However, the substantial difference in the identified volumes of hypoperfused tissue-at-risk may result in largely different clinical decisions and patient outcomes. Further validation efforts (and harmonization of algorithms) are required. Stroke teams should be aware of the limitations of automated analysis and need for expert review.

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Abstract TMP12: Does Prehospital Magnesium Sulfate Differentially Improve Outcome in Hyperacute Stroke Patients With Higher Pretreatment Blood Pressure?

Stroke ◽

10.1161/str.47.suppl_1.tmp12 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Phoebe H Johnson-Black ◽

Sidney Starkman ◽

Nerses Sanossian ◽

David Liebeskind ◽

Samuel Stratton ◽

...

Keyword(s):

Blood Pressure ◽

Cerebrovascular Disease ◽

Acute Stroke ◽

Magnesium Sulfate ◽

Controlled Trial ◽

Functional Independence ◽

Forest Plot ◽

Stroke Patients ◽

Improve Outcome ◽

Acute Cerebral Ischemia

Introduction: Magnesium sulfate (Mg) has blood pressure (BP) lowering, cerebral blood flow enhancing, and neuroprotective effects in preclinical and clinical studies. In the IMAGES phase 3 trial, Mg up to 12h after onset showed no benefit in acute stroke, but was associated with improved outcome in patients with higher blood pressure at entry. Hypothesis: We tested the hypothesis that ultra-early Mg improves functional outcome in acute stroke patients with higher baseline BP. Methods: FAST-MAG is a multicenter, double-blind, randomized, placebo-controlled trial of paramedic-initiated Mg, administered to patients with suspected stroke within 2h of symptom onset. The primary analysis showed neutral effect of Mg. This secondary analysis examines rates of functional independence (mRS 0-2) at 3m for Mg and placebo for different field BP groups. Results: Among 1622 patients with acute cerebrovascular disease, age was 69.6 (±13.4), 42% female, entry deficit severity in the field was LAMS 3.8 (±1.2), and first post-enrollment NIHSS in the ED was 11.5 (±9.9). Systolic blood pressure prior to enrollment was higher among patients with intracerebral hemorrhage (ICH) than acute cerebral ischemia (ACI), 175 (±25) vs 155 (±27), p < .001. The Figure shows the Forest plot for Mg vs placebo and functional independence among blood pressure groups. Heterogeneity of treatment effect was noted in the all-cerebrovascular patients population (p < .01), with fewer independent outcomes with Mg than placebo among patients with higher entry BPs. Analysis of Functional Independence (mRS 0-2) at 90 Days in Prespecified Subgroups Conclusion: This analysis did not confirm the prior finding of magnesium sulfate benefit among acute stroke patients with elevated blood pressure (and actually provided a signal in the opposing direction). Mg was not demonstrated to improve outcome when started in the first 2h of onset among patients with acute cerebrovascular disease and higher blood pressures.

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Abstract WP40: Quick CT Perfusion Evaluation of Leptomeningeal Collateral Circulation: Single Cortical CBV-ROI

Stroke ◽

10.1161/str.48.suppl_1.wp40 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Marta Rubiera ◽

Alvaro Garcia-Tornell ◽

Sandra Boned ◽

Nicolas Romero ◽

Pilar Coscojuela ◽

...

Keyword(s):

Collateral Circulation ◽

Ct Perfusion ◽

Infarct Volume ◽

Accurate Information ◽

Outcome Predictor ◽

Stroke Patients ◽

Quick Method ◽

Accurate Evaluation ◽

The Mean ◽

Contrast Ct

Good collateral circulation (CC) is a strong outcome predictor in acute stroke patients. CT angiography (CTA) is wide-world available but does not provide accurate information about parenchymal status. CT perfusion (CTP) is frequently used to determine ischemic core and tissue at risk. Our aim was to identify an easy and quick method to evaluate CC status by CTP. Methods: Consecutive ischemic stroke patients <8h from symptoms onset evaluated for reperfusion therapies were studied. Non-contrast CT, CTP and multiphase CTA were performed. Patients with confirmed M1-MCA or TICA occlusion on CTA were included. CC evaluation was determined by multiphase CTA (mCTA) according to the Calgary CC Scale and classified as poor (grades 0-2) or good (grades 3-5). In CTP maps, one single ipsi- and contralateral regions of interest (ROI) were defined in the MCA cortical territory (M4, M5, M6). We studied the association of absolute and relative to contralateral ROI-CTP values with CC degree determined by mCTA. Results: 33 patients were included, median NIHSS 17.5 (2-22). Twenty-five patients (75.8%) presented a M1 and 8 (24.2%) a TICA occlusion. On mCTA, 27 (81.8%) patients presented with a favourable CC status and 6 (18.2%) with poor CC. Mean ROI values in the ischemic MCA territory were: CBV 3.5±1.5 ml/100mg, CBF 46.9±29.3 ml/100mg/min, MTT 8.1±3.1 s, Tmax 23.2±4.4 s. In the contralateral non-ischemic MCA, the mean ROI values were: CBV 3.48±1.4, CBF 66.5±32.7, MTT 5.6±2.3, Tmax 20.4±4.8. Absolute and relative CBV-ROI data (relCBV= ischemic CBV value / contralateral CBV value) were the only values significantly associated with CC status on mCTA (good CC mean CBV: 3.8 ml/100g VS poor CC mean CBV: 1.9, p=0.006; good CC mean relCBV 1.1 vs poor CC mean relCBV 0.6, p=0.019). A ROC curve defined 2.5 ml/100mg as the better cut-off point of ROI-CBV that identified patients with good CC status (sensitivity 96%, specificity 84%, VPP 0.96, VPN 0.83). Patients with a ROI-CBV >2.5 presented lower median NIHSS after 24 hours (4 vs 18, p= 0.012) and smaller mean infarct volume on control CT (27.9 vs 88.3, p=0.021). Conclusion: A single cortical ROI-CBV allows an easy and quick accurate evaluation of collateral circulation in CTP. ROI-CBV>2.5 ml/100mg is related to good clinical and radiological outcomes.

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