Sequential carotid Doppler study in acute stroke and its clinical correlation: A prospective study

INTRODUCTION

Cerebrovascular accidents (stroke) constitute a major health issue and are the second most common cause of morbidity and the leading cause of disability worldwide.^[1] With increasing life expectancy in the developing world, there is an increase in age-related non-communicable diseases, making stroke as the fourth leading cause of death in our country.^[2-4] Severity of stroke is objectively quantified by the National Institutes of Health Stroke Scale (NIHSS) and is a major predictor of length of stay (LOS).^[5] LOS >7 days defined as a longer stay depends on the provision of acute stroke care, and preventing complications, which is generally achieved within the 1^st week of the event.^[6] The physiological mechanisms involved in maintaining a constant cerebral blood flow (CBF) and thus, preventing hypo- or hyper-perfusion with changes in cerebral perfusion pressure is disrupted after stroke.^[7] This impaired cerebral autoregulation (CA) has been noted in patients with both ischemic and hemorrhagic strokes.^[7] Dynamic cerebral CA (DCA), the active response of cerebral vessels to blood pressure fluctuations, is also impaired after acute stroke. This jeopardizes the CBF and renders the brain to further injury from edema and hemorrhagic conversion.^[8] DCA can be assessed noninvasively by transcranial Doppler (TCD) sonography that studies spontaneous fluctuations in CBF and blood pressure.^[9] DCA is known to worsen for the first few days after an ischemic stroke. It has been seen to be proportionate to the infarct volume and is associated with a poor outcome.^[10]. Likewise, carotid Doppler is a noninvasive simple, accurate, and reproducible method to assess carotid arteries for evaluating blood flow.^[11,12] It measures peak systolic velocity (PSV), end diastolic velocity (EDV), mean flow velocity (MFV), and peak diastolic velocity which measure the resistive index (RI) and pulsatility index (PI), the most practical parameters for assessing hemodynamic status of the common carotid artery, internal carotid artery (ICA), extracranial carotid artery, vertebral artery, and ophthalmic artery.^[13] PI assesses vascular resistance and is considered a marker of small vessel disease and microangiopathic changes in the brain,^[14,15] whereas RI relates to the vessel wall elasticity.^[16] The normal values for PI and RI are typically <1.2 and <0.7, respectively.^[17] Assessment of PSV, PI, and RI can provide important information for making therapeutic decisions and help as a prognostic tool in predicting functional outcomes in patients of ischemic stroke or after carotid interventions.^[11,18-20] These parameters are related to the NIHSS in a direct relation and can predict the LOS in patients with acute ischemic stroke and hence predict the functional and prognostic outcome in such patients. The present study was done to compare NIHSS, RI, and PI of both ipsilateral and contralateral ICA with the type of stroke (ischemic or hemorrhagic) and duration of hospital stay.

MATERIALS AND METHODS

The present study was conducted at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, a tertiary care referral teaching institute, from February 2020 to July 2021. Patients above 18 years of age who came to the hospital within 48 h of anterior circulation stroke (either ischemic or hemorrhagic) were included in the study. Those coming in the window period were taken up for stroke intervention and excluded. Furthermore, we excluded patients with renal or hepatic failure and those coming with severe cardiorespiratory distress and requiring mechanical ventilation soon after admission.

Patients fulfilling the selection criteria were assessed clinically with NIHSS on days 1, 3, and 5. Carotid Doppler done by an ultrasonologist, blinded to the study, measured ICA Doppler parameters (RI and PI) for both Ipsilateral and Contralateral ICAs on days 1, 3, and 5. Patients were divided into two groups based on their LOS. Patients with LOS <7 days were taken as favorable outcome and those with LOS ≥7 days were grouped as unfavorable outcome.

Duplex Doppler sonography was done using Mindray Ultrasonography machine with 7 megahertz array transducers. Both ipsilateral and contralateral ICAs were scanned following the standard carotid sonography protocol.^[21] Patients were examined in the supine and semi-supine positions with the head slightly rotated to the opposite side. Spectral Doppler scanning was performed to measure the RI and PI of the ICA. The velocity of blood flow was measured in the proximal ICA with a Doppler angle of <60°. RI and PI were calculated from the difference in the systolic and diastolic velocities divided by the MFV and PSV, respectively.^[11]

PI = (PSV–EDV)/MFV

RI = (PSV–EDV)/PSV

NIHSS was used as a measure of severity of stroke with higher scores indicating a poor neurological status and severe deficits.^[22]

RESULTS

One hundred and one patients were included in the study. There were 55 males and 46 females with 65 ischemic and 36 hemorrhagic strokes. Forty-seven patients had a LOS of <7 days (38 ischemic and 9 hemorrhagic stroke) whereas 54 patients had a prolonged LOS of >7 days (27 patients each with ischemic and hemorrhagic stroke). Four patients succumbed to the illness and 97 were discharged in a stable condition.

DISCUSSION

In this study, we evaluated the association of changes in physiological parameters of ICA and NIHSS score with LOS in hospital as a prognostic marker in patients presenting with acute stroke. We found that the markers of peripheral arterial resistance and blood vessel elasticity, PI and RI, decreased over the 5 days in patients with shorter stay compared to an increase in PI in those with prolonged LOS. Although, not all the parameters reached a statistical significance, our findings do indicate that patients with favorable outcomes had reduced peripheral resistance due to reperfusion which led to a decrease in RI. PI showed initial lowering, suggesting dysautoregulation that showed a gradual recovery by the 5^th day of ictus. Likewise, in those with a shorter stay, the NIHSS decreased significantly over 5 days, a marker of clinical improvement.

PI is a marker of increased vascular resistance caused by small vessel disease.^[23] Higher PI is most likely associated with an increase in intracranial pressure and is an independent determinant of volume of infarct in acute stroke.^[24,25] Increase in RI >0.70 and PI >1.35 in the middle cerebral artery (MCA) are prognostic indicators of unfavorable outcome in ischemic stroke.^[1] Soon after stroke, pathophysiological abnormalities in cerebral microcirculation have been postulated to account for the high PI values in large strokes carrying a poor prognosis. Little et al. demonstrated that endothelium and astrocyte end feet get swollen in ischemic stroke.^[26] In addition, despite attempts at reperfusion, the capillary beds narrow segmentally by contraction of pericytes, preventing passage of blood cells, as shown by Yemisci et al.^[27] RI relates to elasticity or extensibility of the vessel and its related vascular resistance.^[16] Tagelsir et al. found a significant increase in RI on carotid Doppler study in fifty Sudanese patients with acute stroke.^[16] Similarly, Staub et al., in a prospective study of 146 patients with cardiovascular risk factors followed up for a median 36 months, showed a direct correlation between RI and intima–media thickness (IMT) of the CCA and ICA and cardiovascular and cerebrovascular events in these patients.^[28] They concluded that like IMT, RI is an indicator of the vessel wall status and can be a predictive marker of stroke. Lin et al. studied 67 ischemic stroke patients, who underwent carotid stenting and found that contralateral ICA RI was the most important indicator for differentiating between patients showing good improvement as against those with static symptoms as measured on modified Rankin score.^[29] We found no statistically significant difference between ipsilateral and contralateral Doppler parameters in the two groups. El Khatib and El Ahwal, contrary to our findings, found a significant difference in the hemodynamic parameters in both ipsilateral and contralateral MCA on 100 patients of acute ischemic stroke.^[19] Similarly, Reinhard et al. demonstrated that in large infarcts, deterioration in autoregulation is more on ipsilateral side.^[30] They used TCD to look at the hemodynamic parameters of the MCA. Our findings were restricted to the neck vessels that probably account for the difference in our findings. NIHSS was seen to decrease in both our groups, but in those with a favorable outcome, the decrease was consistent and statistically significant. Similar findings were observed by Dawodu and Danesi, in their study on patients with ischemic stroke.^[31] LOS is most closely and directly related to the severity of stroke as measured clinically by NIHSS. Koton et al. showed that in patients with a NIHSS of 16–20, the LOS was prolonged by 5 times than those with an NIHSS of 5 or less.^[5]

In our study, patients with a favorable outcome showed a sequential decrease in RI values on days 3 and 5 in ipsilateral ICA whereas PI showed an initial lowering followed by recovery on day 5. For patients having an unfavorable outcome, PI continued to increase on days 3 and 5 probably suggesting a failure of autoregulation.

Our study has a few limitations. The sample size was small and hence an absolute cutoff value of PI and RI could not be determined in this small cohort. A larger study with both ischemic and hemorrhagic strokes with a good follow-up is worthwhile to come to definite standardized values for these predictive markers. Patients were assessed on NIHSS and LOS was determined based only on this clinical indicator. However, in acute stroke, metabolic and septic complications, especially in the acute period, are well-known and these could have been confounders in our study.

CONCLUSION

In patients with acute cerebrovascular events, measuring the hemodynamic parameters in the ICA using a carotid Doppler as a non-invasive, widely available, bedside reproducible tool can help prognosticating patients. For those with an unfavorable outcome and prolonged LOS, PI continues to increase on days 3 and 5, suggesting a failure of autoregulation. This study supports the notion that in addition to NIHSS, a simple objective bedside carotid Doppler study can be a predictor of outcome in patients with acute cerebrovascular episodes.