Relationship between treatment types and blood-brain barrier disruption in patients with acute ischemic stroke:Two case reports

lNTRODUCTlON

Acute ischemic stroke(AIS)is defined as a sudden dysfunction of the central nervous system due to cerebral ischemia and is associated with high mortality and disability rates[1].Minutes after ischemic stroke,dramatic cerebral pathological changes occur at the genomic,molecular,and cellular levels.One of the major pathological changes is the disruption of the blood-brain barrier(BBB)[2].Under pathological conditions,such as ischemic stroke,the BBB can be disrupted,followed by extravasation of blood components into the brain,thereby compromising the normal neuronal function.BBB disruption plays an important role in the development of neurological dysfunction in ischemic stroke[3].However,diagnostic modalities that can clearly diagnose the degree of BBB disruption in ischemic stroke are limited.Dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)is a noninvasive perfusion MRI technique that enables the evaluation of damage to the microcirculatory structure and pathological BBB dysfunction[4].Here,we describe two cases in which the usefulness of DCE-MRI in detecting BBB disruption was evaluated after treatment of AIS using two different methods.

CASE PRESENTATlON

Chief complaints

DCE-MRI was performed after two patients were diagnosed with AIS at the Yeungnam University Medical Center.The BBB permeability(K)was calculated in each patient using the Patlak model[5].

where ,V,and C(t)and C(t)indicate the variable of integration,plasma volume,and temporal variation of the contrast agent of the tissue and plasma,respectively.C(t)was measured in the internal carotid artery with the capillary hematocrit level set at 45%.The average Kvalues were manually segmented and compared.

A 58-year-old man with a chief complaint of motor aphasia was admitted to our emergency department.

A 59-year-old woman with a chief complaint of right hemiparesis and motor aphasia arrived at our emergency department.

The cynic might argue that one can accomplish the same end by shopping at the big-box warehouses9 whose footprints are measured not in square feet, but acres. Well, maybe sometimes, but certainly not always. And the likelihood of feeling forsaken10 in such a wasteland is high.

History of present illness

The patient developed symptoms 9 h before arrival at the hospital.

The patient developed symptoms 10 h before arrival at the hospital.

History of past illness

Diffusion-weighted imaging(DWI)and perfusion-weighted imaging(PWI)showed acute infarctions in the left temporal and insular lobes with no significant DWI-PWI mismatch in the left middle cerebral artery(MCA)territory(Figure 1A and B).

There was no specific medical history.

Physical examination

His National Institute of Health Stroke Scale(NIHSS)score was 3.

The NIHSS score was 4.

Imaging examinations

The only notable medical history was hypertension.

Kim J contributed to conception and design of the study;Huh H and Lee EH organized the database;Kim J and Seo Y wrote the first draft of the manuscript;Huh H,Kim J,Chang MC,and Seo J wrote sections of the manuscript;all authors contributed to manuscript revision,read,and approved the submitted version.

DWI and PWI showed acute infarctions in the left parietal and insular lobes with significant DWI-PWI mismatch in the left MCA territory(Figure 1D and E).

FlNAL DlAGNOSlS

Case 1

Magnetic resonance angiography confirmed occlusion of the M2 inferior trunk of the MCA(Figure 1C).

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Case 2

Considering definite DWI-PWI mismatch,we decided to perform EVT.EVT was performed under local anesthesia.A balloon guide catheter(Optimo,Tokai Medical)was placed in the proximal internal carotid artery through the femoral artery.The balloon of the balloon guide catheter was inflated,and the target vessel was navigated using a 0.014-inch micro-guidewire(Asahi Chikai 10,Asahi Intecc)through the occlusion.A microcatheter(Rebar 18,Medtronic)was then advanced over the wire distal to the occlusion.Selective microcatheter angiography was performed to confirm the occlusion site and distal blood flow.The microcatheter was exchanged for a Solitaire FR(4 × 40).Further,stent-retriever thrombectomy using a Solitaire FR was performed.Finally,reperfusion and good antegrade blood flow were confirmed(Figure 1G).The patient was discharged 1 wk later with no definite neurologic deficits,except mild dysarthria.

TREATMENT

Case 1

Since there was no definite DWI-PWI mismatch,we decided to perform treatment with dual antiplatelet medication without endovascular treatment(EVT).The patient was discharged 1 wk later with no new acute infarction and slight improvement in motor aphasia.

Now on this particular day, it so happened that the Queen lost her favourite ring, and suspicion fell on the confidential servant who had access to all parts of the palace

Case 2

Digital subtraction angiography confirmed the occlusion of the M2 inferior trunk(Figure 2F).

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OUTCOME AND FOLLOW-UP

Case 1 and Case 2

However,it should be noted that studies have found BBB hyperpermeability 3-4 weeks after ischemia onset,indicating that there can be long-term derangement in barrier function[8].Indeed,in patients with stroke,there is evidence that there may be low-level BBB dysfunction at 1 mo[9].Rapid reperfusion after mechanical thrombectomy can result in brain tissue injury[10].Efforts to decrease the duration of BBB disruption could improve clinical outcomes in patients with successful reperfusion.

DlSCUSSlON

BBB disruption begins at the onset of ischemic stroke and increases with sustained hypoperfusion.Maintenance of the BBB immediately after stroke onset might be expected to stop the downstream progression of ischemic brain injury and improve clinical outcomes[2].

BBB disruption is an important component of the pathological progression of AIS and is a potential therapeutic target.Thrombectomy is an interventional means to dislodge and remove the blood clot,and the recent American Heart Association recommendations approve its use up to 24 h after symptoms appear[6,7].The two patients of similar age and relatively similar cerebral infarction locations were treated conservatively or with thrombectomy,although their sex was different.As a result of analysis by performing DCE-MRI,it was confirmed that BBB disruption was significantly less severe in the patient who underwent thrombectomy(= 3.3 × 10),whereas the average Kof the contralateral hemisphere in both patients was similar(2.4 × 10minand 2.0 × 10min).If reperfusion is achieved through thrombectomy,it may indicate that the penumbra can be saved and BBB recovery can be promoted.The reversible BBB disruption may be associated with rapid reperfusion,which is associated with shorter periods of cerebral ischemia.

It is not the same thing. In this chair, I can move by myself; I can go anywhere I need to go. That boat traps me so I can t do anything ?nbsp;I couldn t even save myself if something happened and I fell out.

DCE-MRI was performed after 1 week,the average Kof the entire ischemic region after the treatment was 0.067 ± 0.026 min,whereas that of the contralateral hemisphere was 2.4 × 10min(Figure 2A).DCE-MRI was performed after 1 wk,the average Kof the entire ischemic region after the treatment was 0.0097 ± 0.0024 min,and that of the contralateral hemisphere was 2.0 × 10min(Figure 2B).

The impact of BBB disruption after EVT and outcomes in patients with AIS should be investigated in a larger prospective study.For patients with AIS,BBB protective agents could play an important role and should be investigated in the future.The examination of BBB disruption in the management of AIS is an emerging field of research.With the advancement of DCE-MRI,future research on the BBB is likely to reveal potential therapeutic targets for protecting the BBB and improving outcomes in patients with AIS.

CONCLUSlON

Our cases suggest that BBB disruption could be important if BBB permeability is used to guide clinical treatment.

FOOTNOTES

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the National Research Foundation of Korea grant,No.2019M3E5D1A02069399.

Written informed consent was obtained from the patient for publication of this report and any accompanying images.

He conferred constantly with the doctors. He talked to them about my back surgery, a difficult 12-hour operation to try to relieve the pressure on my spinal cord, and about my medications and my physical therapy. He overruled the doctors on some things, and he was right. He insisted I be taken off radium（）, for example, which they were giving me when they thought I had developed a malignancy（）. In those days, they didn t have the diagnostic tools we have now, or the medications. It turned out I did not have a malignancy, and the radium could have severely4 burned my cord.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The authors have read the CARE Checklist(2016),and the manuscript was prepared and revised according to the CARE Checklist(2016).

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This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial(CC BYNC 4.0)license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited and the use is noncommercial.See:http://creativecommons.org/Licenses/by-nc/4.0/

South Korea

Youngbeom Seo 0000-0001-5568-3636;Jonghoon Kim 0000-0001-9492-6901;Min Cheol Chang 0000-0002-7629-7213;Hyungkyu Huh 0000-0001-6616-5885;Eun-Hee Lee 0000-0003-2297-8280.

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Ma YJ

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Ma YJ