American Heart Association

prognosis

Does Stroke Contribute to Racial Differences in Cognitive Decline?

Rajbeer Singh Sangha, MD

Levine DA, Kabeto M, Langa KM, Lisabeth LD, Rogers MAM, and Galecki AT. Does Stroke Contribute to Racial Differences in Cognitive Decline? Stroke. 2015

The authors of this study tackle the interesting topic of racial disparities in dementia due to the fact that older non-Hispanic blacks have greater risk (approximately 2x) of having cognitive decline, including Alzheimer’s disease and vascular dementia, than older non-Hispanic whites. They investigated whether racial differences in cognitive decline are explained by differences in the frequency or impact of incident stroke between blacks and whites, controlling for baseline cognition. 


The study analyzed 4,908 black and white participants aged 65 and above free of stroke and cognitive impairment. They examined longitudinal changes in global cognition by race, before and after adjusting for time-dependent incident stroke followed by a race-by-incident strokes. They identified 34 of 453 (7.5%) blacks and 300 of 4,455 (6.7%) whites with incident stroke over a mean (SD) of 4.1 (1.9) years of follow-up (P=0.53). Blacks had greater cognitive decline than whites and even with further adjustment for cumulative incidence of stroke, the black-white difference in cognitive decline persisted. While incident stroke was associated with a decrease in global cognition corresponding to approximately 7.9 years of cognitive aging it did not statistically differ by race (P=0.52).

The authors conduct a study which addresses an important issue of whether strokes disproportionately affect cognitive decline in the non-Hispanic black population. The racial disparities that exist in cognitive decline for the two populations would be difficult to discern as the contribution of multiple factors plays a role in the process. Contributions from genetics, socio-economic status and education levels, as well as multiple other factors play a significant role in cognitive decline in racial groups. One of the questions I have for the authors is whether they looked at varying types of cognitive declines (i.e. MCI vs vascular dementia vs Alzheimers) to see if incident stroke played a more significant role in the varying subtypes of dementia. They also acknowledge the limitation that strokes in certain areas were not analyzed as this may predispose an individual to develop more severe deficits in cognition than strokes in other regions. As imaging modalities improve and our understanding of dementia as well as the effect strokes in certain regions of the cerebrum have on functioning, we may be able to better discern the effect of vascular disease on cognitive decline.

Left Atrial Enlargement and Recurrent Stroke

Rizwan Kalani, MD

Yaghi S, P. Moon YP, Mora-McLaughlin C, Willey JZ, Cheung K, Di Tullio MR, et al. Left Atrial Enlargement and Stroke Recurrence: The Northern Manhattan Stroke Study
. Stroke. 2015 

Left atrial enlargement (LAE) is associated with paroxysmal atrial fibrillation (AF), first-ever ischemic stroke, and detection of AF after cryptogenic stroke. In this report, Yaghi et al evaluated the association of LAE and recurrent stroke.

The authors identified first-ever ischemic stroke patients from the Northern Manhattan Stroke Study (NOMASS). 95% of the enrolled patients completed an electrocardiogram and cardiac telemetry monitoring with their first stroke. Transthoracic echocardiogram (TTE) was completed within three months of the initial infarct and the size of the left atrium (LA) was measured by its anteroposterior diameter. In cases where accurate measurement was not possible, a qualitative assessment was completed – there was excellent agreement between the two methods in the patients that had both done. Normal LA size was categorized into four groups – normal, mild LAE, moderate LAE, and severe LAE. Over a five year follow-up period, stroke occurrence and etiologic subtype (based on the TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria) was tracked. The primary outcome for this study was total recurrent ischemic stroke and the secondary outcome was combined recurrent cardioembolic or cryptogenic infarct. 


 

529 patients with a first stroke had LA size data available. The mean age was 69 years and average LA diameter was 40.6 mm (standard deviation 6.3 mm). 279 (53%) had normal LA size, 167 (32%) had mild LAE, and 83 (16%) had moderate-severe LAE. Over a median of 4 year follow-up period, 80 patients (15%) had recurrent stroke; 65 were ischemic, of which 13 were cardioembolic and 16 were cryptogenic. LA diameter and moderate-severe LAE were not associated with the risk of total recurrent ischemic stroke. However, those with moderate-severe LAE had a greater risk of recurrent (combined) cardioembolic or cryptogenic stroke (unadjusted model HR 4.35, 95% CI 1.81-10.48). When adjusting for baseline demographics and risk factors (including AF, heart failure) the association was still present (adjusted HR 2.83, 95% CI 1.03-7.81). Mild LAE was not associated with recurrent cryptogenic or cardioembolic stroke. LA diameter (assessed as a continuous variable) was also associated with a higher risk – adjusted HR 1.55 per SD change in LA diameter (95% CI 1.01-2.37). Finally, none of the patients with moderate-severe LAE were found to have AF at time of recurrent infarct.

This study demonstrates that, in patients with ischemic stroke, moderate-severe LAE is an independent risk factor for recurrent cryptogenic or cardioembolic infarct. Evaluation for LAE, along with other clinical markers of atrial dysfunction – N-terminal pro-brain natriuretic peptide, p-wave terminal force in lead V1 on EKG, and paroxysmal supraventricular tachycardia – may identify a population with elevated risk of stroke even in the absence of paroxysmal AF. This may allow for development of improved risk prediction models for risk of stroke and systemic embolism in patients with an “atrial cardiopathy” (of which paroxysmal AF may only be one manifestation). Additionally, this could identify a group of cryptogenic stroke patients who benefit from anticoagulation over antiplatelet therapy. An important limitation to this study was that prolonged AF monitoring was not routinely conducted, and thus occult AF may not have been detected in some of these patients. Also, LA volume was not assessed in this study, which is a better reflection of LA size than its diameter.

To treat, or not to treat? That’s the question

Chirantan Banerjee, MD

Backes D, Rinkel GJE, van der Schaaf IC, Nij Bijvank JA, Verweij BH, Visser-Meily JMA, et al. Recovery to Preinterventional Functioning, Return-to-Work, and Life Satisfaction After Treatment of Unruptured Aneurysms. Stroke. 2015

The cerebral vasculature, as well as unruptured intracranial aneurysms (UIAs) are complex biologic entities. Their behavior cannot be ascribed to just their location and size. A multidisciplinary international research group published a consensus statement in Stroke (Stroke. 2014;45:1523-1530) in 2014 which echoed this sentiment. We do not have a prospective randomized double blind clinical trial to base decisions on whether and how to treat UIAs. The TEAM trial aimed at assessing the role of prophylactic vascular intervention of UIAs, but never materialized due to poor recruitment. 

In order to advance the science of treating UIAs, we need risk prediction models of rupture. PHASES score was proposed in 2013 by Greving et al where pooled data from 8382 participants in six prospective cohort studies was used, and age, hypertension, history of SAH, aneurysm size, aneurysm location, and geographical region were the predictors of 5 year rupture risk. In addition, risk prediction models for complications of interventions (surgical vs endovascular) are also needed in order to carry out an informed decision analysis on a patient with UIA. In the current study, Backes et al carried out a cross-sectional survey of functional status, working capacity and life satisfaction in 159 patients treated with microsurgery or endovascular intervention for UIA between Jan 1st 2000 and Jan 1st 2013. The questionnaire was sent out in June 2014, and 69% (110) patients responded. 81% patients reported complete recovery after treatment. With regards to life satisfaction (measured using validated LiSat score), patients with high life satisfaction decreased from 76% before treatment to 52% during recovery, and 67% in the long term.

 These findings underlie the important concept that in addition to aneurysm and patient characteristics, treatment effects also should play an integral role in the decision analysis of whether and how to treat a UIA in a patient. An unnecessary intervention may end up doing more harm that good.

Four Year Follow up of Transient Ischemic Attacks, Strokes and Mimics: A Retrospective TIA Clinic Cohort Study

Daniel Korya, MD

Frequently, patients who have transient neurologic symptoms are referred to the emergency department where they may receive further work-up. The usual TIA work-up may ensue after more precise questioning and examination are performed to rule out TIA mimics.

Several studies have been conducted to evaluate the prognosis and outcome of patients after TIA is diagnosed in the hospital or emergency department. The study by Dr. Dutta and colleagues is different because it aimed to determine the prognosis and outcome of patients who were evaluated for TIA at designated daily TIA clinics, based on the EXPRESS study model. 


Although the great majority of patients referred to TIA clinics by non-specialists end up being TIA mimics, there may be a difference in the way they are managed as compared with the ED or hospital. This may be due to the fact that several studies have shown that the TIA mimics are often the result of posterior circulation insufficiency, coronary events or dementia. Therefor a more specialized work-up may be necessary to distinguish these cases.

This study was conducted in the UK and derived data from the TIA clinics of Gloucestershire Royal Hospital (GRH) between April 2010 and May 2012. The majority of practitioners that referred to the GRH were EDs, GPs and paramedics. After a patient was referred to the TIA clinic, they would have their risk factors evaluated, a history and exam would be done along with same-day investigations of CT head, carotid duplex ultrasounds, EKGs as well serum studies. If patients needed MRIs, echocardiograms, Holter monitoring or angiograms, these were done subsequently as required. Patients received treatment the same day as well, with statins, anti-platelet agents or oral anti-coagulants (if AF was diagnosed).

The outcome measures were pre-defined as stroke, MI, any vascular event (TIA, stroke or MI) and all-cause mortality. These were assessed by reviewing hospital records electronically and not by direct patient contact. The investigators looked at subsequent hospital admissions, discharge summaries, outpatient referrals and death. There were no patients lost to follow up and statistical analysis was done by univariate comparison of the TIAs, stokes and mimics with the chi-squared and Kruskal-Wallis tests.


In all, there were 1067 patients that were included in the study who presented to the TIA clinic within the time period of April 2010 and May 2012. Of these patients, 337 were diagnosed with TIA, while 189 were actually strokes and 538 were mimics. The median follow-up period was for 34.9 months. At 90 days, 0.9% of TIAs had a stroke, 2.1% of patients with strokes had a subsequent stroke and 0.2% of mimics had suffered a stroke. Subsequent strokes occurred in 7.1% of patients with TIA, 10.9% of patients with stroke and 2.0% of mimics by the 50-month period of follow up.

Overall, the 90-day risk of subsequent stroke for patients receiving services at these daily TIA clinics was 1.3%. This rate is much lower than that demonstrated by prior studies conducted on TIA patients in the mid-2000s that ranged from 7.5%-9.4%. If these numbers are actually representative of reality, then they imply a reduction of stroke in TIA patients by over 80%!

Why was this number so low compared to historical rates? The investigators believed that this was due to the earlier and more focused treatment of stroke risk factors. These patients received their prescriptions in-hand after their evaluation and were quickly and appropriately assessed in these specialized clinics.

These results sound encouraging and are hinting toward the potential benefit of developing more daily TIA clinics. However, this study should be reproduced in a prospective manner with actual patient assessment and evaluation as opposed to a review of electronic medical records. At any rate, the dramatic reduction of subsequent stroke or MI after TIA as compared to historical controls is promising!

The PHASES score for prediction of intracranial aneurysm growth

The authors of this study make the argument that for most small aneurysms in the anterior circulation, the predicted risk of rupture is much smaller than the risk of treatment complications, and therefore many of these small aneurysms are left untreated. However, a small proportion of these aneurysms do rupture and because these aneurysms by far outnumber other aneurysms, most instances of aneurysmal subarachnoid hemorrhage come from small aneurysms in the anterior circulation. Thus, the need for a better risk prediction model is required. The PHASES score is a model that provides absolute risks of rupture for aneurysms based on six easily retrievable factors which include population, hypertension, age, size of aneurysm, earlier SAH from another aneurysm, site of aneurysm. The score was utilized in this study to see if it is a predictor of aneurysm growth.
 


The authors analyzed a multicenter cohort of patients with unruptured intracranial aneurysms and follow-up imaging with computed tomography angiography or magnetic resonance angiography. They included 557 patients with 734 unruptured aneurysms. Eighty-nine (12%) aneurysms in 87 patients showed growth during a median follow-up of 2.7 patient-years (range 0.5-10.8). Using this cohort, they performed univariable and multivariable Cox regression analyses for the predictors of the PHASES score at baseline, with aneurysm growth as outcome. Per point increase in PHASES score hazard ratio (HR) for aneurysm growth was 1.32 (95% CI: 1.22-1.43). With the lowest quartile of the PHASES score (0-1) as reference, HRs for the second [PHASES 2-3] 1.07 (95% CI: 0.49-2.32), the third [PHASES 4] 2.29 (95% CI: 1.05-4.95), and the fourth quartile [PHASES 5-14] 2.85 (95% CI: 1.43-5.67).
 
It was concluded that this study shows that the PHASES risk score, which provides 5-year absolute risks of aneurysmal rupture, can also be used to identify aneurysms with a high relative risk of aneurysm growth. Despite the strengths of the study, while the PHASES score can be utilized as another surrogate marker for identification of aneurysms that have a higher risk of growth and also an aneurysms risk for rupture, it should be utilized with caution. This score will require further confirmation of its validity before it is implemented on a larger scale as aneurysms should not needlessly be treated give the risks and complications associated with the procedure.

What results in neurological deterioration after spontaneous intracerebral hemorrhage?

Prachi Mehndiratta, MD

Lord AS, Gilmore E, Choi HA, and Mayer SA, on behalf of VISTA-ICH Collaboration. Time Course and Predictors of Neurological Deterioration After Intracerebral Hemorrhage. Stroke. 2015


Spontaneous Intracerebral Hemorrhage (sICH) can be serious and life threatening based on hemorrhage and clinical characteristics. If you remember the Hemphill ICH score, you can predict 30 day mortality from ICH based on a combination of clinical and imaging characteristics. We also know from prior studies that hematomas often snowball and increase in size in the first 24 hours and our best chance of good recovery lies in halting hematoma growth. The authors of this study aim to identify the predictors of neurological deterioration after a sICH. They enrolled patients into a retrospective cohort from the VISTA database and attempted to identify clinical and radiological features associated with a pre-defined neurological deterioration at various points in time. These patients were enrolled in the placebo arms of prospective, randomized trials of acute treatment for ICH and baseline as well as follow up CT scans, rigorous physical exam data and a 3 month mRS score. 



Neurological deterioration (ND) was defined as hyper-acute ( <1 hour), acute (1-24 hours), sub-acute (1-3 days) and delayed (3-15 days). Univariate and multivariate analyses were performed to identify demographic, clinical and radiographic factors that were associated with deterioration in each subgroup. Chi-square, Fisher’s exact test, Mann-Whitney-U test and logistic regression were used for analysis. A total of 376 patients were included in the cohort and ND occurred in 176 patients, 170 at discrete pre specified time points and in 6 patients gradually over multiple time periods. The predictors of ND were intuitive – patients with hyperacute and acute ND had lower GCS, higher NIHSS, larger hematoma volumes and presence of IVH. Patients with subacute ND were similar to those with acute ND but in addition had higher rates of fever and increased IVH blood volumes. Multivariate analysis revealed that delayed ND was associated with older age, higher troponin levels and infection in the 3-15 day period.

The study was well done and well-intended but does it really affect my practice? I don’t think so. I know that patients with certain ICH clinical and radiographic characteristics can get worse and as a stroke physician I need to make sure their hemorrhage volume does not increase, provide them the best supportive neurocritical care and make sure they don’t get infected in order to improve their chances for survival from an illness that already carries a very high morbidity and mortality.

By |February 23rd, 2015|prognosis|1 Comment

No relation of lipid lowering agents to hematoma growth

Rajbeer Singh Sangha, MD

Priglinger M, Arima H, Anderson C, and Krause M. No Relationship of Lipid-Lowering Agents to Hematoma Growth: Pooled Analysisof the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials Studies. Stroke. 2015

Controversy persists over whether statins increase the risk of intracerebral hemorrhage (ICH). A recent systematic overview of randomized trials found no association of statins and the risk of ICH, but less evidence exists for populations with high rates of ICH. Statins do not appear to increase risks of poor functional outcomes in ICH, but no study has examined their association with hematoma growth which may be promoted by ancillary mechanisms. Previous studies have was shown that statins increase fibrinolytic and/or decrease pro-thrombotic mechanisms in vitro. In aortic endothelial cells, statins increase mRNA and enzymatic activity of tissue type plasminogen activator (tPA) (Essig et al., 1998), and decrease mRNA and activity of plasminogen activator inhibitor-type1 (PAI-1) (Bourcier and Libby, 2000). These mechanisms suggest that statins may lead to inhibition of platelet aggregation and thrombogenesis and thereby postulated to affect hematoma growth. The authors of this study examined associations of lipid lowering therapy, hematoma growth and clinical outcomes in participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT).



The authors analyzed the data from the INTERACT trials (1 and 2) which were international, multicenter, open, blinded endpoint, randomized controlled trials with a common protocol that collectively compromised 3243 patients with spontaneous ICH (<6 hours of onset) and elevated systolic blood pressure (SBP 150-220mmHg) randomly allocated to receive intensive or guideline-based BP management. Out of 3184 participants included in the analyses, 204 (6.5%) were on lipid lowering therapy at the time of ICH. 90 day clinical outcomes were not significantly different after adjustment for confounding variables including region and age. In the CT substudy, analysis of 24 hour hematoma growth was greater in 124 patients (9%) with, compared to those without, prior lipid lowering therapy. However, this association was not significant between the two groups (9.2ml vs 6.8ml, p<0.13), after adjustment for prior antithrombotic therapy. This study found no difference in clinical outcomes, initial ICH volume, or 24 hour hematoma volume growth between patients with and without lipid lowering therapy at the time of acute ICH.

After multiple studies, analyses and debates, the evidence seems to be pointing towards the safe utilization of statins during acute ICH. While many of these studies are underpowered to determine a significant effect of statins, the safety profile continues to be established in favor of statin use. It seems that until no large multicenter center does not analyze the effect statins have on ICH we won’t have a conclusive answer and the “controversy” will continue to rage on. Of course, there is the very real possibility that statin use will be limited in the next five years as lipid lowering agents will most likely be comprised of a new class of drugs.

References:
1. Bourcier T, Libby P. HMG-CoA reductase inhibitors reduces plasminogen activator inhibitor-1 expression by human vascular smooth muscle and endothelial cells. Arterioscler Thromb Vasc Biol 2000;20:556–562
2. Essig M, Nguyen G, Prie D, Escoubet B, Sraer J-D, Friedlander G. 3-hydroxy-3-methylglutarylCoenzyme A reductase inhiitors increase fibrinolytic activity in rat aortic endothelial cells. Circ Res 1998;83:683–690.

By |February 17th, 2015|prognosis|0 Comments

Biomarkers Predict Death After Stroke

Rizwan Kalani, MD

Greisenegger S, Segal HC, Burgess AI, Poole DL,  Mehta Z, and Rothwell PM. Biomarkers and Mortality After Transient Ischemic Attack and Minor IschemicStroke: Population-Based Study. Stroke. 2015

Premature death after stroke or TIA is more often a consequence of cardiac disease or malignancy than the cerebrovascular event itself. Prior studies evaluating various serologic biomarkers for predicting recurrent vascular events or death after stroke/TIA have shown mixed results. Greisenegger et al evaluated the association of several biomarkers with all-cause mortality (particularly cardiac or cancer death) in those with minor stroke or TIA.



The cohort studied came from an ongoing population based-study of vascular disease incidence and outcomes in Oxfordshire, UK (Oxford Vascular Study). TIA was defined according to the WHO definition (<24 hours of focal neurological deficit suspected to be of vascular cause – not imaging-based definition that excludes tissue injury) and minor stroke included those with NIHSS<3. Patient death was classified into vascular (stroke, cardiac, etc.) and non-vascular (cancer, other systems) causes. The panel of biomarkers collected are implicated in 1. the inflammatory response – IL-6, CRP, neutrophil-gelatinase associated lipocalin (NGAL), soluble tumor necrosis factor receptor-1 (sTNFR-1); 2. thrombosis – thrombomodulin (TM), fibrinogen, P-selectin, D-dimer, von Willebrand factor (vWF), protein-Z; 3. cardiac function – nt-proBNP; 4. cardiac/neuronal injury – neuron-specific enolase (NSE), heart-type fatty acid binding protein (HFABP); and 5. neural regeneration – BDNF.

929 patients with TIA (47%) and minor stroke (53%) were enrolled. The median age was 74 years and 51% were female. Biomarkers were drawn on average 5 days after the cerebrovascular event; the median follow-up of patients was 6.4 years. 39% (361/929) of patients died during the follow-up period – 151 of vascular cause, 184 non-vascular cause, and 26 unclear etiology. None of the biomarkers correlated with recurrent non-fatal stroke or MI. sTNFR-1, NGAL, CRP, IL-6, vWF, nt-proBNP, and hFABP were predictive of all-cause mortality after adjusting for demographics, risk factors, and prior medical therapy. The strongest associations were for sTNFR-1 (HR 1.45), nt-proBNP (HR 1.44), and hFABP (HR 1.37). sTNFR-1, NGAL, vWF, nt-proBNP, and hFABP were predictive of vascular death in multivariate analysis with the strongest association detected for nt-proBNP (HR 1.8). Among those, all but NGAL were predictive of cardiac death. Nt-proBNP was strongest predictor of stroke-related death. IL-6, CRP, NGAL, sTNFR-1, and hFABP were predictive of non-vascular death. The strongest associations were for hFABP (HR 1.5) and sTNFR-1 (HR 1.47); these two were also predictive of cancer-related death (hFABP HR 1.61, sTNFR-1 HR 1.41). Taken together, sTNFR-1, vWF, hFABP, and nt-proBNP added more prognostic information in comparison to outcome prediction models based on clinical risk factors. These four markers remained predictive of all-cause mortality at 2, 3, and 5 year follow-up.

This study demonstrates that biomarkers related to the inflammatory response, cardiac function, cardiac/neuronal injury, and thrombosis are independent predictors of death in patients with minor stroke or TIA. Those with highest predictive value were sTNFR-1, vWF, nt-proBNP and hFABP. The value of nt-proBNP was shown to be specifically predictive of vascular death and may assist in guiding further cardiac evaluation after stroke. hFABP may be of value for identifying occult malignancy after cerebrovascular ischemia, but this needs to be evaluated in independent cohorts. Future studies will have to validate this and assess the utility of incorporating these biomarkers in clinical care.

By |February 10th, 2015|prognosis|1 Comment

Location, Location, Location: Distance from Carotid Terminus to MCA Clot Predicts Outcome

Mark N. Rubin, MD

Friedrich B, Gawlitza M, Schob S, Hobohm C, Raviolo M, Hoffmann KT, and Lobsien D, Distance to Thrombus in Acute Middle Cerebral Artery Occlusion: A Predictor of Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke. Stroke. 2015


It is well known to strokologists that patients with acute ischemic stroke from proximal occlusions tend to fare poorly as compared to those with distal occlusions. Several prospective and retrospective observational studies have confirmed this relationship. What has been lacking, however, is precision in the definition of “proximal occlusion,” as seen with the heterogeneity of definitions across trials and observational studies.



This interesting CTA-based imaging study sought to rigidly stratify occlusion location by distance from a single anatomical landmark: the middle of the “carotid T.” In a standardized fashion, the investigators looked back at CTA studies from 136 patients who received IV tPA and measured from the midpoint of the distal ICA to the proximal end of a clot and compared that distance to 7-day NIHSS and 90-day mRS. Overall, the main finding was the distance from the carotid T to the clot was an independent predictor of outcome, even when controlling for clot length. There was an exponential decline in likelihood of good outcome (mRS < or = 2) with distance to thrombus of <16mm. Short distance to thrombus also predicted long thrombus length as compared to more distal occlusions.

In addition to assisting in the definition of proximal occlusions with discrete measurements and a practical anatomical landmark for standardization, this investigation also suggests that perhaps we should pay more attention to clot location and length in our treatment trials and natural history studies, as evidence mounts that these data are quite relevant.

By |February 9th, 2015|prognosis|0 Comments

Responsiveness after Hemorrhagic Stroke – Role of the Frontal Networks

Rizwan Kalani, MD

Mikell CB, Banks GP, Frey HP, Youngerman BE, Nelp TB, Karas PJ, et al. Frontal Networks Associated With Command Following After Hemorrhagic Stroke. Stroke. 2014

We often assess level of arousal by a patient’s ability to follow commands. In this study, Mikell et al evaluated which brain structures are necessary to follow commands in the setting of acute intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) using a multimodality approach – a combination of structural and functional MRI (fMRI) as well as continuous EEG monitoring.


Data from 25 patients with spontaneous ICH or SAH that completed all components of the multi-modality testing were analyzed from a prospective, single-center database. 9 patients (36%) were unresponsive (unable to follow simple, 1-step commands) and 16 were awake at time of testing. Structural injury to the pons, midbrain, and thalamus was initially evaluated (by lesion volume quantification) using structural MRI. Resting state fMRI was then used to identify which brain networks were disrupted in the unresponsive patients compared to those who were awake. The relationship between the default mode network (DMN – the brain regions active when a person is awake and at rest) and the task-positive network (TPN – areas responding to attention-demanding tasks) were evaluated. Lastly, continuous EEG was used to confirm changes in functional connectivity seen.

There was no significant difference between the hemorrhage sizes of the unresponsive and awake patients. 6 functional networks were impaired in unresponsive patients by fMRI – these were located in the premotor, dorsal anterior cingulate, and supplementary motor areas. Connectivity between the DMN and right orbitofrontal cortex was decreased in unresponsive patients. Interestingly, new connections between the TPN and DMN were seen in unresponsive patients that were not seen in those who were awake. These findings were supported by EEG coherence data.

This manuscript suggests that disruption of frontal network connectivity (instead of the actual structural injury) accounts for unresponsiveness in the setting of ICH/SAH. It supports the idea that altered connectivity to (rather than within) the DMN is lost in an unresponsive state. Future studies will need to evaluate the mechanisms by which these network connectivity changes occur and how each individual network involved affects consciousness. The principal limitations of this study are the small number of patients included and inability to evaluate the effect of intracranial pressure on the findings.

By |December 10th, 2014|prognosis|0 Comments