Chronic Cerebral Ischemia Treatment

Chronic Cerebral Ischemia Treatment

see also Acute Ischemic Stroke Treatment.


Carotid artery stenting

Revascularization for Chronic Cerebral Ischemia Treatment.

The role of cellular transplantation to promote functional recovery after stroke has been evaluated over the last two decades. Preclinical studies first established the potential for cultured neuronal cells derived from a teratocarcinoma cell line to be tested for safety and efficacy in the treatment of human stroke. In animal models of stroke that caused reproducible learning and motor deficits, injection of neuronal cells resulted in a return of learning behavior, retention time, and motor function. Clinical trials followed. Additional work with cells derived from a bone marrow neuroprogenitor line, fetal cortical stem cells, and other cell sources showed promise in preclinical studies and then these cells were tested in clinical studies 1).

prospective randomized trial (NCT03745092) enrolled 50 cases of CCI patients, which were divided into NBO (8 L/min of oxygen supplement) group and control group (room air) randomly, and also enrolled 21 healthy volunteers. Two times of 30-min EEG recordings with the interval of 45min of NBO or room air were analyzed quantitatively.

The CCI-mediated EEG presented with two patterns of electrical activities: high-power oscillations (high-power EEG, n = 26) and paroxysmal slow activities under the normal-power background (normal-power EEG, n = 24). The fronto-central absolute power (AP) of the beta, alpha, theta, and delta in the high-power EEG was higher than that in healthy EEG (p < 0.05). The fronto-central theta/alpha, delta/alpha and (delta + theta)/(alpha + beta) ratios in the normal-power EEG were higher than those in healthy EEG (p < 0.05). The high-power EEG in NBO group had higher fronto-central AP reduction rates than those in control group (p < 0.05). NBO remarkably reduced the fronto-central theta/alpha, delta/alpha, and (delta + theta)/(alpha + beta) ratios in the normal-power EEG (p < 0.05).

NBO rapidly ameliorates CCI-mediated EEG anomalies, including attenuation of the abnormal high-power oscillations and the paroxysmal slow activities associated with CCI 2).


1)

Kondziolka D. Stem Cell Treatment for Ischemic Stroke Recovery. Semin Neurol. 2021 Jan 27. doi: 10.1055/s-0040-1722640. Epub ahead of print. PMID: 33506475.
2)

Ding JY, Liu Y, Rajah GB, Chen ZY, Zhang SY, Ding YC, Ji XM, Meng R. Normobaric oxygen may correct chronic cerebral ischemia-mediated EEG anomalies. CNS Neurosci Ther. 2021 Jul 9. doi: 10.1111/cns.13703. Epub ahead of print. PMID: 34242498.

Quantitative electroencephalography for delayed cerebral ischemia diagnosis

Quantitative electroencephalography for delayed cerebral ischemia diagnosis

The association between alpha-delta ratio (ADR) on quantitative electroencephalography (EEG) and DCI has been reported in several previous studies, but their results are conflicting 1).


Focal reduction in alpha power may represent a valid, observer-independent, non-invasive and continuous marker for vasospasm/DCI in SAH patients 2).

A prolonged alpha-theta/delta (AT/D) ratio decrease seems to be a reliable biomarker of DCI 3).


In a study, Mueller et al. aimed to compare and analyze the ability of qEEG and transcranial color-coded duplex ultrasonography (TCD/TCCS) to early identify patients who will develop later manifest cerebral infarction.

They analyzed cohorts of two previous qEEG studies. Continuous six-channel-EEG with artifact rejection and a detrending procedure was applied. Alpha power decline of ≥ 40% for ≥ 5 hours compared to a 6-hour-baseline was defined as a significant EEG event. Median reduction and duration of alpha power decrease in each channel were determined. Vasospasm was diagnosed by TCD/TCCS, identifying the maximum frequency and days of vasospasm in each territory.

34 patients were included (17 male, mean age 56 ± 11 years, Hunt and Hess grade: I-V, cerebral infarction: 9). Maximum frequencies in TCD/TCCS and alpha power reduction in qEEG were correlated (r = 0.43; p = 0.015). Patients with and without infarction significantly differed in qEEG parameters (maximum alpha power decrease: 78% vs 64%, p = 0.019; summed hours of alpha power decline: 236 hours vs 39 hours, p = 0.006) but showed no significant differences in TCD/TCCS parameters.

There was a moderate correlation between TCD/TCCS frequencies and qEEG alpha power reduction but only qEEG differentiated between patients with and without cerebral infarction.

Significance: qEEG represents a non-invasive, continuous tool to identify patients at risk of cerebral infarction 4).


1)

Yu Z, Wen D, Zheng J, Guo R, Li H, You C, Ma L. The predictive accuracy of alpha-delta ratio on quantitative electroencephalography for delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage: a meta-analysis. World Neurosurg. 2019 Feb 27. pii: S1878-8750(19)30493-0. doi: 10.1016/j.wneu.2019.02.082. [Epub ahead of print] PubMed PMID: 30825635.
2)

Gollwitzer S, Groemer T, Rampp S, Hagge M, Olmes D, Huttner HB, Schwab S, Madžar D, Hopfengaertner R, Hamer HM. Early prediction of delayed cerebral ischemia in subarachnoid hemorrhage based on quantitative EEG: A prospective study in adults. Clin Neurophysiol. 2015 Aug;126(8):1514-23. doi: 10.1016/j.clinph.2014.10.215. Epub 2014 Nov 14. PMID: 25500193.
3)

Balança B, Dailler F, Boulogne S, Ritzenthaler T, Gobert F, Rheims S, Andre-Obadia N. Diagnostic accuracy of quantitative EEG to detect delayed cerebral ischemia after subarachnoid hemorrhage: A preliminary study. Clin Neurophysiol. 2018 Sep;129(9):1926-1936. doi: 10.1016/j.clinph.2018.06.013. Epub 2018 Jul 5. PMID: 30007892.
4)

Mueller TM, Gollwitzer S, Hopfengärtner R, Rampp S, Lang JD, Stritzelberger J, Madžar D, Reindl C, Sprügel MI, Dogan Onugoren M, Muehlen I, Kuramatsu JB, Schwab S, Huttner HB, Hamer HM. Alpha power decrease in quantitative EEG detects development of cerebral infarction after subarachnoid hemorrhage early. Clin Neurophysiol. 2021 Mar 26:S1388-2457(21)00465-X. doi: 10.1016/j.clinph.2021.03.005. Epub ahead of print. PMID: 33867261.

Delayed cerebral ischemia diagnosis

Delayed cerebral ischemia diagnosis

Local intraparenchymal neuromonitoring in the anterior cerebral artery/middle cerebral artery watershed area might detect the vast majority of delayed cerebral ischemias for all intracranial aneurysm locations, except for basilar artery aneurysms. In ACA and AcomA aneurysms, bilateral DCI of the ACA territory was common, and bilateral probe positioning might be considered for monitoring high-risk patients. Non-focal monitoring methods might be preferably used after BA aneurysm rupture 1).


Evaluating the proportion of the brain with critical hypoperfusion after SAH may better capture the extent of DCI than averaging CBF across heterogenous brain regions 2).

Early low CBF measurements and a high lactate and lactate to pyruvate ratio may be early warning signs of the risk of developing Delayed cerebral ischemia (DCI). The clinical value of these findings needs to be confirmed in larger studies 3).

Transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS) are noninvasive modalities that can be used to assess vasospasm. However, high flow velocity does not always reflect DCI.

Significant literature shows that perfusion computed tomography (CTP) can provide sufficient information on cerebral hemodynamics and effectively indicate delayed cerebral ischemia (DCI) before the development of infarction. Sun et al. aimed at performing a meta-analysis to provide a more full and accurate evaluation of CTP and CTP parameters in detecting DCI in patients with aneurysmal subarachnoid hemorrhage.

In the PubMed, MedLine, Embase and Cochrane databases analysis published from February 2005 to February 2013. The extraction of CTP parameters, including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), interhemispheric ratios for CBV and CBF and interhemispheric differences for MTT and TTP. Pooled estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the summary receiver-operating characteristic curve were determined.

Four research studies are met the inclusion criteria for the analysis. The pooled sensitivity, specificity, PLR, NLR and DOR of CTP for detecting the DCI were 82%, 82%, 4.56, 0.22 and 20.96, respectively. Through the evaluation of absolute CTP parameters, CBF and MTT showed diagnostic value for DCI, but CBF and TTP did not. Moreover, CBF ratio, MTT difference and TTP difference showed more diagnostic value than CBV ratio in DCI detection by the assessment of relative CTP parameters.

As a non-invasive and short time consuming screening method, CTP own a high diagnostic value for the detection of DCI after aneurysm rupture 4).

CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers.

Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm.

Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose 5).


Whole-brain CT Perfusion (CTP) on Day 3 after aneurysmal subarachnoid hemorrhage (aSAH) allows early and reliable identification of patients at risk for delayed ischemic neurological deficits (DIND) and tissue at risk for delayed cerebral infarction (DCI) 6).


The association between alpha-delta ratio (ADR) on quantitative electroencephalography (EEG) and DCI has been reported in several previous studies, but their results are conflicting 7).


1)

Hurth H, Steiner J, Birkenhauer U, Roder C, Hauser TK, Ernemann U, Tatagiba M, Ebner FH. Relationship of the vascular territory affected by delayed cerebral ischemia and the location of the ruptured aneurysm in patients with aneurysmal subarachnoid hemorrhage. Neurosurg Rev. 2021 Mar 29. doi: 10.1007/s10143-021-01522-4. Epub ahead of print. PMID: 33782797.
2)

Jafri H, Diringer MN, Allen M, Zazulia AR, Zipfel GJ, Dhar R. Burden of cerebral hypoperfusion in patients with delayed cerebral ischemia after subarachnoid hemorrhage. J Neurosurg. 2019 May 31:1-8. doi: 10.3171/2019.3.JNS183041. [Epub ahead of print] PubMed PMID: 31151110.
3)

Rostami E, Engquist H, Howells T, Johnson U, Ronne-Engström E, Nilsson P, Hillered L, Lewén A, Enblad P. Early low cerebral blood flow and high cerebral lactate: prediction of delayed cerebral ischemia in subarachnoid hemorrhage. J Neurosurg. 2017 Jun 2:1-9. doi: 10.3171/2016.11.JNS161140. [Epub ahead of print] PubMed PMID: 28574309.
4)

Sun H, Zhang H, Ma J, Liu Y, Wang K, You C. Accuracy of computed tomography perfusion in detecting delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage: a meta-analysis. Neurol India. 2013 Sep-Oct;61(5):507-12. doi: 10.4103/0028-3886.121922. PubMed PMID: 24262454.
5)

Cremers CH, Dankbaar JW, Vergouwen MD, Vos PC, Bennink E, Rinkel GJ, Velthuis BK, van der Schaaf IC. Different CT perfusion algorithms in the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology. 2015 Jan 23. [Epub ahead of print] PubMed PMID: 25614332.
6)

Malinova V, Dolatowski K, Schramm P, Moerer O, Rohde V, Mielke D. Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage. J Neurosurg. 2015 Dec 18:1-9. [Epub ahead of print] PubMed PMID: 26684786.
7)

Yu Z, Wen D, Zheng J, Guo R, Li H, You C, Ma L. The predictive accuracy of alpha-delta ratio on quantitative electroencephalography for delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage: a meta-analysis. World Neurosurg. 2019 Feb 27. pii: S1878-8750(19)30493-0. doi: 10.1016/j.wneu.2019.02.082. [Epub ahead of print] PubMed PMID: 30825635.
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