American Heart Association

Monthly Archives: January 2016

Lesions of the precental gyrus are predictive of apraxia of speech

Peggy Nguyen, MD

Itabashi R, Nishio Y, Kataoka Y, Yazawa Y, Furui E, Matsuda M, and Mori E. Damage to the Left Precentral Gyrus Is Associated With Apraxia of Speech in Acute Stroke. Stroke. 2016 

Apraxia of speech (AOS) differs from aphasia of speech in that while aphasia denotes an inability to understand and or use language, AOS denotes impairment in the motor initiation and execution needed to produce speech, which leads to impaired speech rate and rhythm and inability to produce the desired speech sound. This neurologic deficit has been poorly localized in the past; to better address this, the authors selected cases of first ever, non-lacunar left MCA ischemic strokes and characterized the location of lesion using voxel based lesion-symptom mapping in patients with AOS versus those without AOS.

In the selected 136 cases, 3 groups were identified: (1) pure AOS n = 7, (2) AOS with aphasia, n = 15, and (3) non-AOS, n = 114. Patients with AOS (both with and without aphasia) had lesions involving the posterior wall of the left precentral gyrus in the central sulcus. Notably, when there was a lesion of the posterior wall of the left precentral gyrus, this was predictive of the presence of AOS in comparison between pure AOS and non-AOS. No brain regions associated with pure AOS were detected, but scattered subcortical brain regions, including basal ganglia and corona radiate were detected in association with AOS-aphasia.

This study builds on the background of the vague neuroanatomical localization of language itself, but does suggest that a lesion in the left precentral gyrus is predictive of the development of AOS. While it may not impact clinical management as of yet, it does lead us to a better neuroanatomical understanding of language. Certainly therapeutic approaches to AOS do differ from aphasia, in that the emphasis lies on teaching rate and rhythm of speech and production of sound as opposed to restoring language ability, and it is conceivable that this may help guide prognosis and therapeutic approaches.

By |January 29th, 2016|clinical|2 Comments
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Magnetic resonance “black blood” thrombus imaging found to have high sensitivity and specificity for cerebral venous sinus thrombosis in small prospective study

Danny R. Rose, Jr., MD

Yang Q, Duan J, Fan Z, Qu X, Xie Y, Nguyen C, et al. Early Detection and Quantification of Cerebral Venous Thrombosis by Magnetic Resonance Black-Blood Thrombus Imaging. Stroke. 2016

Cerebral venous sinus thrombosis (CVST) is a relatively rare form of stroke that typically affects young individuals. Improved methods of diagnosis and treatment have significantly improved outcomes of CVST, but current indirect noninvasive imaging that relies on visualizing venous flow perturbation can lead to delays that may result in increased morbidity and mortality. Magnetic resonance direct thrombus imaging (MRDTI) may improve upon this through its ability to visualize thrombus directly by exploiting the short T1 relaxation time of methemoglobin within the thrombus. To date there has been little study using this imaging modality in the cerebral venous system. Yang et al. sought to investigate the ability of MRDTI (using a so-called “black-blood MR technique” or “MRBTI”) to detect CVST in a prospective study comparing this technique to traditional diagnostic imaging.



Forty-seven patients with signs and symptoms suspicious for CVST were recruited for the study. All patients received CT, MR and Time of Flight MR venography, with five patients also receiving a contrast enhanced CT venogram as well. Two readers performed a consensus reading of all conventional imaging studies with full clinical and outcome information, with a total of 14 venous segments being assessed for thrombi based on the presence or absence of intraluminal filling defects. MRBTI was performed using 3D variable-flip-angle turbo spin echo on a 3.0T scanner. MRBTI images were randomized and presented to two independent readers who were blinded to the diagnostic/therapeutic management of the patients, clinical information and conventional imaging data. Image quality was rated on a 4 point scale with 4 being excellent with no relevant artifacts. The presence or absence of thrombus was recorded for each of the 14 segments assessed via conventional imaging. Patients with CVST detected by MRBTI were divided into two groups based on duration of clinical onset: ≤ 7 days and between 7-30 days.

With conventional imaging, a total of 116 thrombosed venous segments were identified among 23 patients. MRBTI correctly identified 113 out of 116 segments, resulting in a sensitivity of 97.4%. In 527 out of 531 segments, CVST was ruled out correctly with a specificity of 99.3%. Using patient based parameters MRBTI correctly identified all 23 patients with CVST. One false-positive and zero false-negatives were identified, resulting in a sensitivity of 100% and specificity of 95.8%. There were no issues with image quality—647 of 658 segments (98%) were diagnostic according to the 4 point rating scale, and the overall image quality score was 3.5±0.6. Signal-to-noise and contrast-to-noise ratio, another metric of image quality comparing the signal intensity of the thrombus to that of adjacent tissue, was found to have significant differences in all signal measurements taken.

Utilizing MRBTI in CVST was found to approach the high diagnostic accuracy of conventional imaging in this small prospective study. Patients who stand to benefit most include those with renal impairment, which may serve as a contraindication to contrasted imaging, as well as pregnant patients and others where radiation exposure should be avoided. The utility of MRBTI may also extend to monitoring for thrombus progression/resolution, as this imaging modality is able to calculate thrombus volume as well. One significant limitation of the study that limits its widespread use is the use of a 3.0T MRI, which is seldom found outside of academic institutions and tertiary care centers. Other limitations to this study stem primarily stem from the use of a single center and small sample size, thus validation of this study in a multicenter prospective study with a larger enrollment is crucial.

By |January 28th, 2016|diagnosis and imaging|Comments Off on Magnetic resonance “black blood” thrombus imaging found to have high sensitivity and specificity for cerebral venous sinus thrombosis in small prospective study
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Predicting convalescent rehabilitation outcomes in ischemic stroke patients

Luciana Catanese, MD

Senda J, Ito K, Kotake T, Kanamori M, Kishimoto H, Kadono I, et al. Association of Leukoaraiosis With Convalescent Rehabilitation Outcome in Patients With Ischemic Stroke. Stroke. 2016

Stroke continues to be a leading cause of disability worldwide. Indeed, a large number of patients who have suffered an ischemic stroke are unable to return to their homes, requiring disposition to acute rehabilitation facilities. The imaging predictors of good outcomes in acute ischemic stroke (AIS) patients undergoing convalescent rehabilitation are yet to be determined.

In this issue of Stroke, Senda et al. investigated the factors influencing convalescent rehabilitation outcomes in AIS patients focusing on imaging parameters such as degree and type of leukoaraiosis and stroke subtypes. Retrospective data from consecutive AIS subjects, who were hospitalized in a single rehabilitation center in Japan from January 2008 to December 2013, was included. The enrolled individuals were right-handed, completely independent (mRS 0 and Barthel Index of 100) at baseline, had an available brain MRI/MRA, were not discharged prematurely and did not carry a diagnosis of dementia. The Functional Independence Measure (FIM) score both on admission and at discharge was used as the measure of functional outcome. The authors classified stroke subtypes by etiology including lacunar infarcts (LI), atherothrombotic (AT), artery-artery embolism (A-to-A), cardioembolic (CE), undetermined embolism (UN) and “other”, if a specific mechanism such as vasculitis or postoperative stroke was suspected. Baseline demographic data was obtained from the initial hospitalization records. White matter lesions were graded on T2 or FLAIR sequences as periventricular (PV) or deep white matter hyperintensity (DWMH) using the Fazekas scale. Finally, the presence of ≥ 50% stenosis in the intracranial cerebral vasculature was considered “stenosis positive”. A stepwise multiple regression analysis was performed to characterize the relationships between the independent variables (total, cognitive and motor FIM scores at baseline, prior medications, age, sex, history of stroke, heart disease and tobacco, side of stroke, presence of unilateral or bilateral strokes, PVH and DWMH grade, atrial fibrillation and presence of significant stenosis on MRA) and the total, motor and cognitive FIM scores on both admission and at discharge. UN and other ischemic stroke groups were excluded from this analysis.

A total of 520 patients (317 men, 203 women; mean age 72.8 years) were included. The average number of days from symptom onset to transfer to rehabilitation was 32.8 +/- 10.3 days and the mean inpatient rehabilitation time was 112 +/- 20 days. Overall, hypertension was overrepresented in the LI group, diabetes in the A-to-A group and higher grades of PHV and DWMH in the LI and A-to-A group. As expected, positive arterial stenosis was more frequently seen in the A-to-A group. There was no significant difference in FIM scores among stroke subtypes. When looking at the total FIM scores at discharge, higher grades of PVH, age and the FIM scores on admission were strongly associated with worse outcomes. In the subgroup analysis of individual stroke subtypes, history of stroke was a significant predictor of worse rehabilitation outcomes in the A-to-A group. In regard to FIM motor scores, PVH grade, presence of bilateral ischemic strokes and history of stroke were factors significantly associated with worse outcomes. In the subgroup analysis, the presence of significant stenosis and PVH grade were predictors of poor outcomes in the AT and A-to-A group, respectively. Finally, age and hypertension medications correlated with worse outcomes as measured by the FIM cognitive scores. In the stroke subtypes analysis, history of tobacco and DWMH grade were significantly associated with worse outcomes in the CE and A-to-A groups.

Overall, the degree of leukoaraiosis on MRI as measured by the Fazekas scale appears to strongly correlate with worse functional outcomes in convalescent acute ischemic stroke patients. This data is not only in line with available literature such as that shown in the Leukoaraiosis and disability (LADIS) cohort study, but it also supports the usefulness of MRI when estimating functional outcomes. In addition to that, the authors found that PVH grade appeared to be associated with motor-function outcomes whereas DWMH correlated with cognitive function outcome. This study is not without limitations, the retrospective and single-center design, multiple subgroup analysis without correction for multiple testing and potential for residual confounding – to name a few – limit the interpretation of the findings and highlight the need for long-awaited prospective trials on the subject. Predicting functional outcomes in the convalescent rehabilitation period is of utmost importance for our stroke patients, and systems resource management.

By |January 27th, 2016|diagnosis and imaging|1 Comment
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Large penumbral volumes do not preclude good outcomes after complete reperfusion

Jay Shah, MD

Nogueira RG, Haussen DC, Dehkharghani S, Rebello LC, Lima A, Bowen M, et al. Large Volumes of Critically Hypoperfused Penumbral Tissue Do Not Preclude Good Outcomes After Complete Endovascular Reperfusion: Redefining Malignant Profile. Stroke. 2016

Reperfusion in acute ischemic stroke is a fine balance between improved clinical outcomes and potential reperfusion injury. Therefore, judicious patient selection is essential. Pooled analysis from both DEFUSE and EPITHET studies confirmed poor outcomes in patients achieving reperfusion with malignant profile. This profile was defined with perfusion volumes of 85 cc and greater. The DEFUSE trial also defined a target mismatch profile that could distinguish ideal candidates for reperfusion therapy. However, this was derived from perfusion imaging that used a Tmax > 10 second threshold. This threshold was established in the pre-stent retriever era which is known to result in faster and better reperfusion. In this study, the authors evaluated the impact of the malignant profile using Tmax > 10s lesion on outcomes of patients undergoing complete reperfusion with stent retrievers.

This was a retrospective review from a database of patients with anterior circulation large-vessel occlusion that underwent CT perfusion imaging and achieved full reperfusion. Follow-up MRI were obtained to determine final infarct volume. The primary outcome was impact of Tmax >10s lesion on infarct growth. In total, 113 patients were included. Patients with malignant profile lesions had larger baseline and core infarct volumes. However, there were no significant differences in absolute volume of infarct growth, 90-day mortality or severe intracranial hemorrhage.

This study suggests that large volumes of severely hypoperfused tissue on CT perfusion are not associated with higher rates of infarct growth, severe hemorrhage, or unfavorable outcomes as long as there is not a large baseline ischemic core. The implications of this study is important in that patients who may potentially benefit from reperfusion therapy should not be excluded. Since reperfusion therapy has been proven to demonstrate clinical efficacy, the focus has appropriately been on ideal patient selection. This study is limited by its relatively small size, retrospective nature, and small percentage of patients receiving intravenous thrombolytics. This latter limitation may confound the findings in that thrombolytic remains the first line therapy as long as no absolute contraindications are present. Future prospective trials are needed to determine ideal endovascular candidates.

By |January 26th, 2016|treatment|Comments Off on Large penumbral volumes do not preclude good outcomes after complete reperfusion
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Only 27% of death after stroke can be attributed to modifiable risk factors


In this issue of Stroke, Marileen Portegies and colleagues seek to determine the theoretical impact of pre-morbid cardiovascular risk factors on mortality after stroke. 

The study population was the well-described prospective, population-based Rotterdam cohort. Each patient with incident stroke was age and sex matched with four stroke-free participants. Poisson regression was used to determine age and sex adjusted mortality rate ratios. Interactive Risk Attributable Program, a method to calculate population attributable risks, was used to determine the population attributable risk for each vascular risk factor and for all risk factors (those independently contributing to mortality) combined. Interaction term analysis evaluated for effect modification by stroke.


For this study, they included 1,237 stroke patients and 4,928 non-stroke participants. The mean age was 80 years, and 60.4% were female. Cardiovascular risk factors were measured for a mean of 3.7 (±3.2) years before stroke.

Mortality rates after stroke were highest in the first 30 days and remained double that of the non-stroke group 1 year onward from inclusion. The increased mortality after stroke was largely due to cardiovascular death.

The population attributable risks for the most important modifiable risk factors were as follows:
  • Smoking: 0.13 (in other words, 13% of post-stroke mortality can be attributed to pre-stroke smoking status)
  • Diabetes: 0.06
  • Atrial fibrillation: 0.06
  • Hypertension: 0.06

The cumulative proportion of mortality of included vascular risk factors was 0.27 (95% confidence interval, 0.14-0.45). This means that 27% of post-stroke mortality can be attributed to pre-existing modifiable risk factors. This was only 8% higher than the attributable risk in patients without stroke.

The authors acknowledge that population attributable risks of certain risk factors were driven by the increased prevalence of these risk factors in patients with stroke.

The authors keenly point out that the main conclusion here is that 73% of post-stroke mortality is not explained by premorbid cardiovascular risk factors. Understanding the “other 73%” may yield stroke-specific actionable targets to reduce post-stroke mortality.
By |January 25th, 2016|prevention|1 Comment
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D-4F is a promising neuroprotectant for stroke recovery

Peggy Nguyen, MD

Cui X, Chopp M, Zacharek A, Cui C, Yan T, Ning R, and Chen J. D-4F Decreases White Matter Damage After Stroke in Mice. Stroke. 2016

D-4F, an apolipoprotein analogue, has been studied as a potential therapy in the treatment of atherosclerosis. Prior studies suggest that D-4F may enhance HDL function, which could be potential target for neuroprotection in stroke. Here, the authors investigated the in vivo effect of D-4F on serum biomarkers, stroke outcome, inflammation and white matter recovery in a mouse stroke mode. Significantly, they found:

  • D-4F treatment at all dosages (2, 4, 8, 16 and 32 mg/kg daily for 7 days) had no significant effect on serum levels of HDL, total cholesterol, triglyceride and infarction volume but treatment at 16 mg/kg daily for 7 days did improve functional outcome after stroke as measured by the modified Neurological Severity Score (mNSS) at 7 days and as measured by the foot-fault test at 3 and 7 days after stroke.
  • D-4F treatment decreased white matter damage and increased oligodencrocyte progenitor cells after stroke. Accordingly, a better functional outcome (lower mNSS) significantly correlated with higher axonal density.
  • D-4F treatment decreased inflammatory markers TLR4 and TNFα but increased IGF1, which promotes neuronal and oligodendrocyte differentiation, proliferation, myelination and may serve as the pathway for via which D-4F treatment exerts its protective effects.

Both D-4F and IGF1 treatment of primary cortical neuron cultures in vitro increased neurite outgrowth significantly.

So far, none of the investigated neuroprotectants have been proven to be beneficial for stroke outcomes. Although this study is obviously limited by its subjects (being mouse models), the results show promise in identification of a possible neuroprotectant for stroke.

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By |January 22nd, 2016|basic sciences|3 Comments
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Location, Location, Location: Post-Stroke Cognitive Outcome Determined by Location of Stroke

Ilana Spokoyny, MD

Munsch F, Sagnier S, Asselineau J, Bigourdan A, Guttmann CR, Debruxelles S, et al. Stroke Location Is an Independent Predictor of Cognitive Outcome. Stroke. 2016 
 

The ability to predict post-stroke functional and cognitive outcomes would be very useful in guiding patients and families as to the course of their post-stroke recovery. Specific anatomic locations, predominantly in the left hemisphere, affect language and cognitive processing and it is plausible that injury to those specific areas would disproportionately affect cognitive outcomes. However, damage to other areas may disrupt network functioning and cause global cognitive impairment.

This study sought out to identify and characterize the contribution of functionally important brain areas on cognitive and functional outcomes at 3 months post-stroke. Patients were included who had with no previous disability (modified Rankin Scale/mRS=0) with supratentorial ischemic strokes. Patients with severe cognitive impairment at baseline were excluded. Each patient had an MRI done between 24-72 hours post stroke. The authors determined functionally eloquent areas of brain by calculating the probability that functional scores (in this case mRS or MoCA-Montreal Cognitive Assessment) would worsen if that voxel of brain tissue was affected by an ischemic lesion. Then, maps were created based on this information, a technique known as voxel-based lesion symptom mapping. The information from 215 of the 289 patients was used to create the maps, and the other patients were used as an independent population for validation of the method. The maps for both mRS and MoCA showed a predominance of eloquent brain tissue in the left hemisphere. This lateralization was stronger in the MoCA maps, likely due to language localization.

Multivariable analyses were performed to determine whether stroke location (using number of eloquent voxels as per the VLSM maps), age, NIHSS, and stroke volume predicted good 3 month functional (mRS 0-1) and cognitive (MoCA>25) outcomes. Another cognitive score was calculated, sMoCA, which removed naming and language from the MoCA, to isolate the non-aphasia components.

Stroke location did not hold up to multivariable analysis as an independent predictor of mRS at 3 months; functional outcome was mostly predicted by NIHSS. Stroke location was, however, the strongest independent predictor of cognitive outcome (MoCA score) at 3 months. In patients with MoCA >25 (good outcome), a median of only 2 eloquent voxels were affected, compared with 224 eloquent voxels for MoCA ≤ 25. Including stroke location in the model also improved the predictive ability of non-language cognitive performance (represented by sMoCA), demonstrating that overall cognitive function, not just aphasia, was influenced by stroke location.

Limitations of this study include the use of a somewhat crude functional outcome score (mRS). It is possible that using a more detailed motor or ADL score would have been better predicted by stroke location. In the future, it would be interesting to create a map based on a larger population, and determine the predictive ability of stroke location on cognitive and functional outcomes.

By |January 21st, 2016|diagnosis and imaging|Comments Off on Location, Location, Location: Post-Stroke Cognitive Outcome Determined by Location of Stroke
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Neurofibromatosis type 1 and its relationship with stroke

Allison E. Arch, MD

Terry AR, Jordan JT, Schwamm L, and Plotkin SR. Increased Risk of Cerebrovascular Disease Among Patients With Neurofibromatosis Type 1: Population-Based Approach. Stroke. 2016

Neurofibromatosis type I (NF1) is associated with multiple different tumor types. As it turns out, it may also be associated with vasculopathy and stroke. The link between NF1 and vascular events has been previously addressed in the literature, but it remains poorly understood. In this article, Terry and colleagues explored the relationship between NF1 and stroke in a case-control study. The authors used the population in the US Nationwide Inpatient Sample to screen for NF1 admissions between 1998 – 2009. Then they matched controls to cases in a 5:1 ratio, using the variables age, gender, geographic region, hospital size, and hospital type (rural, urban non-teaching, or urban teaching).

The results showed that NF1 was associated with an increased odds of stroke in hospitalized patients, most notably hemorrhagic strokes. The odds of any stroke was 1.2 (p<0.0001), and the odds of intracerebral hemorrhage was 1.9 (p<0.0001). Patients with NF1 had strokes at a younger age, and the adult patients with NF1 and stroke had a lower prevalence of stroke risk factors, including a lower prevalence of diabetes, atherosclerosis, and atrial fibrillation.

This is a significant finding. Currently, if a patient with NF1 presents with acute neurologic findings, tumor and tumor-associated morbidities are highest on the differential diagnosis. However, if NF1 is also associated with stroke, then vascular events should now also be considered.

By |January 20th, 2016|epidemiology and genetics|Comments Off on Neurofibromatosis type 1 and its relationship with stroke
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Vagus nerve stimulation paired with arm rehabilitation shows promise in small safety/feasibility study

  Danny R. Rose, Jr., MD

Dawson J, Pierce D, Dixit A, Kimberley TJ, Robertson M, Tarver B, et al. Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke. Stroke. 2016

Arm weakness is common after stroke and can result in significant disability for affected patients. Current rehabilitative strategies centered on intensive, repetitive, and task-specific activities have shown only modest benefit–only 40% of stroke survivors with non-functional arms at one week are able to recover function by 6 months. These therapies have been shown to facilitate neuronal plasticity, but currently there are no proven methods to augment this plasticity to enhance recovery. Developing more efficacious ways of recovering motor function could lead to significant quality of life improvements for stroke survivors and reduction in healthcare costs and medical co-morbidities associated with loss of
independence.

Vagus nerve stimulation (VNS) has been proposed as a potential adjunctive therapy, as it activates neurons in the basal forebrain and locus coeruleus that facilitate reorganization of cortical networks. Preliminary animal studies have shown that pairing forelimb rehabilitation with VNS significantly increases recovery of speed and strength compared to rehabilitation alone. Dawson et al. sought to begin investigating the potential for VNS therapy to improve upper limb rehabilitation in patients with chronic stroke by conducting a small safety and feasibility study with a randomized open active comparator design.

Patients considered for inclusion were 18-80 years of age with a history of unilateral supra-tentorial ischemic stroke occurring at least 6 months prior. The Action Research Arm Test (ARAT) score was used to determine eligibility with respect to arm impairment, using a score of 15-50 indicating moderate to severe impairment. Twenty participants were randomized. Eleven were randomized to receive rehabilitation alone, consisting of a six week course of two-hour therapy sessions three times per week that focused on repetition of seven standardized tasks, and nine were randomized to receive the same therapy after VNS implantation, with the therapist delivering 500 millisecond bursts of VNS manually when the patient performed the rehabilitative tasks. One patient in the VNS group received medications that may interfere with VNS and was excluded from the per-protocol analysis. Outcome assessments were performed on days one, seven, and 30 after the conclusion of therapy in both groups and included the aforementioned ARAT score as well as upper extremity Fugl-Meyer assessment, Stroke Impact Scale (SIS), grip and pinch strength as assessed by a handheld dynamometer, Box and Block test, 9-hole peg test, and robotic assessment using an InMotion Technologies robot.

A total of 22 adverse events (AEs) were reported in the eight participants in the VNS group compared to ten AEs in three participants in the rehabilitation only group. Two participants suffered a serious adverse event in the VNS group and one participant suffered four SAEs in the rehabilitation group, with none of them being related to device effects or the rehabilitative therapy. Adverse device effects were minor and all resolved, although one participant suffered temporary left vocal cord palsy and dysphagia and had their VNS stopped in case it would hinder recovery.

The mean change in FMA-UE scores in the VNS group was +8.7 (5.8) vs. +3.0 (6.1) in the rehab only group (p=0.064), with the per-protocol analysis showing a statistically significant improvement in the VNS group (+9.6[5.3] vs +3.0[6.1], p=0.038). There were no significant differences in the other secondary efficacy endpoints. Although baseline imaging characteristics between the two groups were similar, VNS responders had significantly higher infarct volumes as compared to rehabilitation only responders (p<0.05).

This study represents an exciting novel therapy with dramatic implications for motor recovery following stroke. The statistically significant improvement in the per-protocol analysis suggests the potential of a more appreciable effect in a study with a larger sample size. The significantly higher infarct volume in VNS responders suggests that VNS may enhance recovery in patients with larger strokes that tend to benefit less from rehabilitative therapy alone. As VNS is already widely used in refractory epilepsy with a proven safety record, the lack of concerning adverse effects is not surprising. As this is an entirely new application for VNS therapy, further protocol refinement to establish VNS parameters for further study is needed.

By |January 19th, 2016|treatment|2 Comments
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Administration of transdermal glycerol trinitrate does not affect functional outcomes in patients with ICH

Alexander E. Merkler, MD

Krishnan K, Scutt P, Woodhouse L, Adami A, Becker JL, Berge E, et al. Glyceryl Trinitrate for Acute Intracerebral Hemorrhage: Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis. Stroke. 2016

Outcomes in patients with intracerebral hemorrhage (ICH) are poor; more than two-thirds of survivors with ICH are left disabled at three months and less than half of patients with ICH are alive at 1 year. Ongoing research continues to address ways to improve outcomes – one such approach is acute blood pressure reduction. High blood pressure is common in acute ICH and is associated with worse outcomes, at least in part through hematoma expansion. Previous trials such as INTERACT have shown a trend towards improved functional outcomes using intensive BP lowering within the first 6 hours after ICH, but management of high BP in acute ICH remains uncertain.


The current subgroup analysis of the ENOS (Efficacy of Nitric Oxide in Stroke) trial evaluates the impact of transdermal glyceryl trinitrate (GTN) in patients with ICH. ENOS was a large multicenter trial that evaluated BP reduction in patients with both ischemic stroke and ICH using GTN. When GTN was given within 48 hours of stroke onset, BP was significantly reduced at day 1; however, functional outcome at 90 days was no different. When GTN was given within six hours of stroke though, functional outcomes were improved. In this current manuscript, the authors performed a pre-specified subgroup analysis, evaluating whether use of GTN in patients with ICH improved functional outcomes both overall, and within 6 hours of having an ICH.

629 patients with ICH presenting within 48 hours and initial SBP >140mmHg were included. Patients were randomized to receive GTN transdermally for one week versus no GTN. The mean time to randomization was 25 hours. 87% of hemorrhages were deep and 26% of patients had IVH. BP was significantly lower following the first dose of GTN versus no GTN (7.5/4.2 mmHg).

Overall, at 90 days, the median mRS was the same (3) in both the GTN and no GTN groups. In addition, there were no differences between secondary outcomes such as measures of disability, cognition, mood and quality of life. No differences in serious adverse events were seen.

Of the 61 (9.7%) patients randomized within 6 hours (and in whom the average time to treatment was 4.4 hours), patients randomized to GTN had an improved functional outcome as manifested by a positive shift on the mRS, improved mood and quality of life and reduced death.

GTN is a useful transdermal agent to acutely lower BP and does not seem to have serious adverse effects. The study adds further support that early BP lowering in patients with ICH may improve functional outcomes.

By |January 15th, 2016|hemorrhage|Comments Off on Administration of transdermal glycerol trinitrate does not affect functional outcomes in patients with ICH
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