F. Statistical analysis
III. RESULTS
A. Comparison between the all included patient
548 patients with acute ischemic stroke with anterior circulation fulfilled the selection criteria and were included in this study. 91 were included in the hypothermia group, and 457 were in the untreated group. Table 1 showed demographics and clinical characteristics between the hypothermia and no hypothermia groups. Age and sex were unbalanced between the two groups, so additional statistical matching was required and will be introduced in the next part.
General stroke risk factors and the ratio of patients with prior antiplatelet or anticoagulant use were similar in the two groups. There was no difference in premorbid mRS and initial NIHSS in both groups.
The TH group (vs. NH group) showed significantly different distribution of stroke etiology (p=0.001), 78 embolism patients (86.2%), 8 ICAS patients (9.9%), and 4 other etiology patients (4.4%).
Laboratory, radiological and treatment related parameters were presented in Table 2. In laboratory parameters, other results of patients were similar in the two groups. Baseline ASPECT score and DWI volume was significantly different between groups. TH group (vs. NH group) was worse ASPECT score (5 vs. 7, p<0.001) and large DWI volume (55.22±47.60 vs. 24.59±47.79, p<0.001).
Time parameters of EVT were unbalanced also, onset to puncture time, onset to reperfusion time were different between two groups. As for the EVT method, stent retrieval was used in the TH group (68.1%) vs. 36.8%). In addition, the HT group (vs. NH group) had more IV-rtPA use (64.8% vs. 52.1%, p=0.026).
In the clinical outcome (Table 3), good (mRS 0-2) outcome at 3 month were found to be worse in the hypothermia group (38.5% vs. 55.0%, p=0.004). These results suggest that the baseline characteristics are largely affected. There is a mismatch of baseline characteristics, so matching is performed for comparison of the clinical outcomes. Even after adjusting baseline demographics as a conventional propensity method of 1:2 matching, clinical outcome was the same as before the matching.
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Figure 2. The histogram of propensity score matching between two groups after 1:2 matching in all-included patient
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Table 1. Comparison of demographics and baseline characteristics between the hypothermia and no hypothermia groups
HTN = hypertension, DM = diabetes mellitus, TIA = Transient ischemic attack, mRS = modified Rankin scale, NIHSS = National Institutes of Health Stroke Scale, LAA = large artery atherosclerosis;
*independent t-test, †Pearson’s chi-square test, §Mann-Whitney U test
Before matching After matching (1:2)
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Table 2. Comparison of laboratory, radiological and treatment parameters between the hypothermia and no hypothermia groups
WBC = white blood cell, LDL = low-density lipoprotein, ESR = erythrocyte sedimentation rate, CRP = C-reactive protein, INR = international normalized ratio, PTT = partial thromboplastin time, ASPECT = Alberta Stroke program early CT score;
*independent t-test, †Pearson’s chi-square test, §Mann-Whitney U test
Before matching After matching (1:2)
Glucose (mg/dL) 134.01±42.69 140.27±55.99 0.313* 134.01±42.69 138.26±54.95 0.540*
HbA1c (%) 6.116±0.93 6.19±1.19 0.553* 6.116±0.93 6.160±1.28 0.637*
WBC 8.35±2.69 8.53±3.13 0.617* 8.35±2.69 8.66±3.44 0.752*
Hemoglobin 13.58±1.56 13.39±1.88 0.340* 13.58±1.56 13.58±1.97 0.933*
Hematocrit 40.41±4.78 39.54±5.30 0.150* 40.41±4.78 40.12±5.51 0.653*
Platelet 214.58±58.99 225.70±71.95 0.167* 214.58±58.99 224.10±71.90 0.220*
Total cholesterol 166.89±38.00 166.48±40.00 0.928* 166.89±38.00 168.37±39.40 0.963*
LDL 97.81±35.56 102.08±36.74 0.312* 97.81±35.56 102.41±36.89 0.329*
ESR (mg/dL) 15.74±16.66 15.17±15.48 0.755* 15.74±16.66 12.45±13.82 0.034*
CRP 0.55±1.13 0.82±2.01 0.075* 0.55±1.13 0.56±1.28 0.002*
INR 1.09±0.25 1.09±0.24 0.976* 1.09±0.25 1.10±0.24 0.568*
PTT 30.13±5.88 28.02±13.74 0.150* 30.13±5.88 26.89±4.74 <0.001*
Radiological parameters
Baseline DWI vol. 55.22±47.60 24.59±47.79 <0.001* 55.22±47.60 37.82±64.73 <0.001*
Endovascular therapy, n (%) <0.001§ <0.001§
Retrieval stent 62 (68.1) 168 (36.8) 62 (68.1) 75 (41.2) Aspiration 19 (20.9) 175 (38.3) 19 (20.9) 74 (40.7)
Others 10 (11.0) 114 (24.9) 10 (11.0) 33 (18.1)
Time parameters, min, median (range)
Onset to puncture 285.01±193.72 342.35±228.61 0.014* 285.01±193.72 302.57±195.91 0.548*
Onset to reperfusion 354.65±199.52 415.32±324.35 0.011* 354.65±199.52 375.53±207.82 0.453*
IV-rtPA use 59 (64.8) 238 (52.1) 0.026† 59 (64.8) 114 (62.6) 0.722†
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Table 3. Clinical outcome between the hypothermia and no hypothermia groups
mTICI = modified thrombolysis in cerebral infarction, HI = hemorrhagic infarct, PH = parenchymal hematoma, HT
= hemorrhagic transformation, DWI = diffusion-weighted imaging, mRS = modified Rankin Scale;
*independent t-test, †Pearson’s chi-square test, §Mann-Whitney U test
Before matching After matching (1:2)
DWI change 44.55±60.11 35.86±58.98 0.264* 44.55±60.11 40.89±55.89 0.646*
Clinical outcome
mRS (0-1) at 3 month 22 (24.2) 170 (37.2) 0.017† 22 (24.2) 70 (38.5) 0.019†
mRS (0-2) at 3 month 35 (38.5) 251 (55.0) 0.004† 35 (38.5) 101 (55.5) 0.008†
mRS (0-3) at 3 month 50 (54.9) 295 (64.6) 0.083† 50 (54.9) 120 (65.9) 0.077†
Mortality at 3 month 9 (9.9) 51 (11.2) 0.718† 9 (9.9) 18 (9.9) 1.000†
１４ B. Non-malignant MCA group and hypothermia
A total of 468 patients were included in the non-malignant MCA infarction group except for 80 patients who met the malignant trait described previously. Propensity score matching was performed to overcome the bias of the baseline covariates of the two groups. Figure 3 presented with histogram of propensity score matching between two groups after matching. It is seen that the distribution of the two groups is relatively even compared with that of the former group.
Table 4 showed demographics and clinical characteristics, Table 5 showed laboratory, radiological and treatment related parameters between the hypothermia and no hypothermia groups of non-malignant MCA infarction patients. The mismatch of age, gender, atrial fibrillation, stroke etiology, and baseline ASPECTS was resolved through propensity score matching. However, after 1:2 matching, the bias of baseline DWI volume (p<0.001) and EVT method (p<0.001) could not be resolved.
Clinical outcome between the TH and NH groups of non-malignant MCA infarction assessed by various methods (Table 6). Successful reperfusion and symptomatic hemorrhagic transformation (PH type2) was not differ between the two groups. But, TH group (vs. NH group) was worse when compared no hemorrhage than any types of hemorrhagic transformation (57.1 % vs. 69.8%, p=0.083). And, good (mRS 0-2) outcome at 3 month were found to be worse in the TH group (41.3% vs. 65.2%, p=0.002).
.
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Figure 3. The histogram of propensity score matching between two groups after 1:2 matching in non-malignant MCA infarction
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Table 4. Comparison of demographics and baseline characteristics between the hypothermia and no hypothermia groups of non-malignant MCA group (before and after 1:2 matching)
HTN = hypertension, DM = diabetes mellitus, TIA = Transient ischemic attack, mRS = modified Rankin scale, NIHSS
= National Institutes of Health Stroke Scale, LAA = large artery atherosclerosis;
*independent t-test, †Pearson’s chi-square test, §Mann-Whitney U test
Before matching After matching (1:2)
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Table 5. Comparison of laboratory, radiological and treatment parameters between the hypothermia and no hypothermia groups of non-malignant MCA group (before and after 1:2 matching)
Glucose (mg/dL) 137.13±46.82 138.59±55.02 0.842* 137.13±46.82 144.71±61.75 0.386*
HbA1c (%) 6.16±0.96 6.17±1.18 0.931* 6.16±0.96 6.28±1.27 0.921*
WBC 8.35±2.71 8.42±2.96 0.852* 8.35±2.71 8.82±3.49 0.642*
Hemoglobin 13.62±1.56 13.48±1.84 0.558* 13.62±1.56 13.54±2.04 0.679*
Hematocrit 40.53±4.87 39.73±5.19 0.251* 40.53±4.87 40.00±5.75 0.427*
Platelet 221.71±55.74 225.31±72.17 0.650* 221.71±55.74 222.32±81.35 0.737*
Total cholesterol 170.02±38.47 166.65±40.60 0.539* 170.02±38.47 163.44±36.45 0.241*
LDL 98.93±36.01 101.99±37.25 0.546* 98.93±36.01 97.04±36.22 0.608*
ESR (mg/dL) 15.48±14.80 14.70±14.99 0.704* 15.48±14.80 12.70±13.19 0.148*
CRP 0.65±1.33 0.79±1.98 0.584* 0.65±1.33 0.83±1.97 0.001*
INR 1.11±0.27 1.09±0.25 0.702* 1.11±0.27 1.14±0.28 0.185*
PTT 30.45±6.64 28.23±14.50 0.234* 30.45±6.64 27.54±4.84 <0.001*
Radiological parameters
Baseline DWI vol. 32.89±23.70 13.89±16.06 <0.001* 32.89±23.70 18.66±19.72 <0.001*
Endovascular therapy, n (%) <0.001§ <0.001§
Retrieval stent 44 (69.8) 139 (34.3) 44 (69.8) 41 (32.5) Aspiration 13 (20.6) 163 (40.2) 13 (20.6) 63 (50.0)
Others 6 (9.5) 103 (25.4) 6 (9.5) 22 (17.5)
Time parameters, min, median (range)
Onset to puncture 314.46±215.43 341.10±227.41 0.384* 314.46±215.43 328.97±218.00 0.930*
Onset to reperfusion 384.75±220.58 410.83±232.07 0.404* 384.75±220.58 393.59±219.92 0.980*
IV-rtPA use 37 (58.7) 209 (51.6) 0.292† 37 (58.7) 67 (53.2) 0.469†
WBC = white blood cell, LDL = low-density lipoprotein, ESR = erythrocyte sedimentation rate, CRP = C-reactive protein, INR = international normalized ratio, PTT = partial thromboplastin time, ASPECT = Alberta Stroke program early CT score; *independent t-test, †Pearson’s chi-square test, §Mann-Whitney U test
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Table 6. Clinical outcome between the hypothermia and no hypothermia groups and no hypothermia groups of non-malignant MCA group (before and after 1:2 matching)
mTICI = modified thrombolysis in cerebral infarction, HI = hemorrhagic infarct, PH = parenchymal hematoma, HT
= hemorrhagic transformation, DWI = diffusion-weighted imaging, mRS = modified Rankin Scale;
*independent t-test, †Pearson’s chi-square test, §Mann-Whitney U test
Before matching After matching (1:2)
DWI change 42.09±59.24 31.86±53.63 0.216 42.09±59.24 27.08±36.18 0.245 Clinical outcome
mRS (0-1) at 3 month 18 (28.6) 169 (41.7) 0.047† 18 (28.6) 55 (43.7) 0.045†
mRS (0-2) at 3 month 26 (41.3) 247 (61.1) 0.003† 26 (41.3) 82 (65.2) 0.002†
mRS (0-3) at 3 month 38 (6.03) 281 (69.4) 0.151† 38 (6.03) 95 (75.4) 0.032†
Mortality at 3 month 3 (4.8) 36 (8.9) 0.268† 3 (4.8) 10 (7.9) 0.549†
１９ C. Malignant MCA infarction and hypothermia
Among anterior circulation ischemic stroke patients, 80 patients were diagnosed as malignant MCA infarction. Twenty-eight patients had received TH. Table 7 showed demographics and clinical characteristics between the TH and NH groups of malignant MCA infarct. Demographics and baseline characteristics differed in several variables. Age, diabetes, baseline NIHSS score, stroke etiology were unbalanced between the two groups. Table 8 showed laboratory, radiological and treatment related parameters. In laboratory parameters, other results of patients were similar in the two groups except glucose, C-reactive protein (CRP) and partial thromboplastin time (PTT). In time parameters, TH group (vs. NH group) had significantly short onset to puncture time (218.75±109.26 vs. 352.04±239.80, p=0.001) and onset to reperfusion time (286.93±118.72 vs. 450.23±251.05, p<0.001).
Clinical outcome between the TH and NH groups were meaningful (Table 9). TH group (vs. NH group) had a better clinical outcome (32.1% vs. 7.7% p=0.009) and a lower frequency of hemorrhagic transformation (none vs. any hemorrhage, p=0.007). Decompressive hemicraniectomy rate (n=5, 17.9% vs.
n=6, 11.5%, p=0.503) and mortality (n=6, 21.4% vs. n=15, 28.8%, p=0.472) were not different (Table 9).
To find prognostic factors for good clinical outcome, potential factors that were significant in the univariate analyses entered multivariate logistic regression with stepwise-backward conditional mode (Table 10). After adjusting potential confounders to predict good outcome, therapeutic hypothermia (OR 4.63; CI 1.20-17.89; p=0.026) and hypertension (OR 0.18; CI 0.04-0.74; p=0.018) were independent determinants.
２０
HTN = hypertension, DM = diabetes mellitus, TIA = Transient ischemic attack, mRS = modified Rankin scale, NIHSS
= National Institutes of Health Stroke Scale, LAA = large artery atherosclerosis;
*independent t-test, †Pearson’s chi-square test, §Mann-Whitney U test
Table 7. Comparison of demographics and baseline characteristics between the hypothermia and no hypothermia groups with malignant MCA infarction
TH (n=28)
NH
(n=52) P value
Age, yrs, median (range) 65.07±13.43 71.1 ±11.47 0.038*
Sex, female, n (%) 12 (42.9) 28 (53.8) 0.348†
Baseline NIHSS, median (range) 19 [15.3-21] 21 [18-22] 0.013§
Stroke etiology, n (%) 0.030§
Embolism 25 (89.3) 35 (67.3)
LAA 2 (7.1) 9 (17.3)
Others 1 (3.6) 8 (15.4)
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Table 8. Comparison of laboratory, radiological and treatment parameters between the hypothermia and no hypothermia groups with malignant MCA infarction
TH
Baseline DWI vol. 104.84±50.14 112.62±102.28 0.714§
Endovascular therapy, n (%) 0.417§
Retrieval stent 18 (64.3) 29 (55.8)
Aspiration 6 (21.4) 12 (23.1)
Others 4 (14.3) 11 (21.2)
Time parameters, min, median (range)
Onset to puncture 218.75±109.26 352.04±239.80 0.001*
Onset to reperfusion 286.93±118.72 450.23± 251.05 <0.001*
IV-rtPA use 22 (78.6) 29 (55.8) 0.043†
WBC = white blood cell, LDL = low-density lipoprotein, ESR = erythrocyte sedimentation rate, CRP = C-reactive protein, INR = international normalized ratio, PTT = partial thromboplastin time, ASPECT = Alberta Stroke program early CT score; *independent t-test, †Pearson’s chi-square test, §Mann-Whitney U test
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Table 9. Clinical outcome between the hypothermia and no hypothermia groups with malignant MCA infarction
DWI change 50.82±63.39 89.84±94.15 0.127*
Clinical outcome
mTICI = modified thrombolysis in cerebral infarction, HI = hemorrhagic infarct, PH = parenchymal hematoma, HT
= hemorrhagic transformation, DWI = diffusion-weighted imaging, mRS = modified Rankin Scale;
*independent t-test, †Pearson’s chi-square test, ‡Fisher’s exact test
２３
Figure 4. Distribution of hemorrhagic transformation between the hypothermia and no hypothermia groups with malignant MCA infarction
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Non-TH (n=52) TH (n=28)
No hemorrhage HT type 1 HT type 2 PH type 1 PH type 2
２４
Figure 5. Distribution of 3-month modified Rankin Scale between the hypothermia and no hypothermia groups with malignant MCA infarction
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Non-TH (n=52) TH (n=28)
mRS0 mRS1 mRS2 mRS3 mRS4 mRS5 mRS6
２５
Table 10. Multivariate Logistic Regression Analysis for Prediction of Good Outcome (mRS, 0–2) Characteristics Good outcome
DWI volume 93.62±34.52 113.25±93.46 0.46 0.99 (0.98-1.00) 0.457
Hypothermia 9 (69.2) 19 (28.4) 0.009 5.68 (1.56-20.69) 0.008 4.63 (1.20-17.89) 0.026
Onset to puncture 217.62±100.75 322.42±224.86 0.105 0.99 (0.99-1.00) 0.110
Onset to reperfusion 275.00±118.93 415.99±236.58 0.040 0.99 (0.98-1.00) 0.042 … …
ASPECTS = Alberta Stroke Program Early CT Score; CI = confidence interval; CT = computed tomography; DWI = diffusion-weighted imaging; HT = hemorrhagic transformation; ICA = internal carotid artery; NIHSS = National Institutes of Health Stroke Scale; OR = odds ratio; TICI, thrombolysis in cerebral ischemia; IV-rtPA = intravenous recombinant tissue-type plasminogen activator, and ICAS = intracranial arterial stenosis.
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IV. DISCUSSION
This study demonstrated that therapeutic hypothermia led to reduction of hemorrhagic transformation and improvement of clinical outcomes in malignant MCA infarction patients who treated with EVT. In addition, therapeutic hypothermia was an independent predictor of good outcome after adjustment of potential confounding factors.
A. Unmet need for additional treatment of acute ischemic stroke
Even after the remarkable achievement of EVT, a considerable number of stroke patients still disabled despite a higher reperfusion rate. In addition, the usefulness of EVT in patients with large core infarct was still under discussion. Several previous studies in patients with a malignant MCA infarct trait represented by low ASPECT have shown poor outcomes despite reperfusion (Goyal M et al., 2011; Yoo AJ et al., 2014; Inoue M et al., 2014). On the contrary, EVT was found to be useful in patients with a large core volume greater than 70 mL, and reperfusion rate was a predictor of good outcome (Chen Z et al., 2018).
These results demonstrates that reperfusion itself does not always guarantee a good functional outcome, especially in patients with ‘malignant MCA infarction trait’. To improve clinical outcome, neuroprotection after recanalization is drawing attention in the era of EVT. The previous failure of neuroprotective drugs can be overcome by the achievement of recanalization same as preclinical ischemic-reperfusion model (Chamorro et al., 2016). Among the neuroprotective strategies, immediate post-reperfusion cooling is encouraging as an option to minimize reperfusion-related complications.
B. Neuroprotective mechanism and effect of therapeutic hypothermia on various conditions
TH is used as neuroprotective therapy in various situations such as traumatic brain injury, brain damage after cardiac arrest, as well as stroke. TH has a multi-target neuroprotective effect. It is involved in the ischemic phase where excitotoxicity, apoptosis, inflammation and free radical production occur, or it
２７
affects neurogenesis, gliogenesis and angiogenesis after injury (Yenari et al., 2012). After ischemic insult, decrease of cerebral blood flow ensues ionic homeostasis disruption and calcium influx (Khanna et al., 2014; Lai et al., 2014). Intracellular calcium permit the release of excitatory neurotransmitters, mitochondrial dysfunction, and increase of reactive oxygen species generation (Globus et al., 1995;
Gonzalez-Ibarra et al., 2011). The cerebral metabolic rate is important in ischemia-reperfusion status.
Hypothermia reduces oxygen and energy demands as body temperature decreases by 1℃, resulting 6-7%
decrease in cerebral metabolic rate (Polderman et al., 2009). It also reverse transport of glutamate by suppression of excitatory neurotransmitter release and reduction in glutamate receptor expression.(Kim et al., 2011; Wang et al., 2013) In addition, hypothermia attenuates the inflammatory response by suppression of astrocyte and microglial activation (Xiong et al., 2011).
Numerous preclinical and clinical studies have proved the neuroprotective efficacy of TH on various conditions. TH is applied as standard treatment in patients with coma after cardiac arrest (Bernard et al., 2002). In experimental stroke models, TH has been shown to be helpful as a potent neuroprotectant, especially in ischemia-reperfusion models (Yenari et al., 2012). These results were in accordance with several clinical researches in acute ischemic stroke (Hong et al., 2014; Hwang et al., 2017). However, the efficacy of TH in ischemic stroke is still open to question (Liu et al., 2016) because some studies have reported a harmful systemic effect of TH, such as pneumonia (Lyden et al., 2016), cardiopulmonary problems (De Georgia et al., 2004), and immune suppression (Liu et al., 2016).
C. Therapeutic hypothermia in non-malignant MCA infarction
In this study, we focused on determining the population who can benefit from neuroprotection.
Subgroup analysis revealed that ischemic stroke patients who had non-malignant trait showed a poor prognosis in hypothermia group. This can be explained for the following reasons. First, baseline characteristics between the hypothermia and no hypothermia groups were considerably different. The hypothermia group had more common sources of cardioembolism, more severe ischemic change in ASPECTS, and more prevalent hemorrhagic transformation. It means that clinicians conducted TH in
２８
patients who had severe reperfusion injury. We executed propensity score matching to overcome these imbalance, however, substantial differences of the baseline characteristics were not balanced after matching.
Second, TH can be associated with various medical complications. Low temperature can predispose stroke patients to systemic infections by inhibiting the cytokine response and stimulating anti-inflammatory cytokines (Lee et al., 2001; Russwurm et al., 2002). Although hypothermia treatment has not been reported to increase the risk of infection in systemic review and meta-analysis study, (Den Hertog et al., 2009) several clinical studies described the higher incidence of pneumonia in patients treated with hypothermia (De Georgia et al., 2004; Polderman et al., 2009). Hemodynamic changes, including decreased heart rate and arrhythmias, can be problematic during hypothermia treatment (De Georgia et al., 2004; Staikou et al., 2011). This phenomenon is related to the temperature level, the degree of hypothermia treatment should be controlled with caution. Various other side effects including electrolyte imbalance, cold diuresis, and alterations in coagulation cascade can affect the clinical outcome of patients treated with hypothermia treatment.
D. Therapeutic hypothermia in malignant MCA infarction
Our study showed that TH can lead to good clinical outcome in patients with malignant MCA infarction. There are efforts to apply the clinical effect of TH to malignant MCA infarction (Georgiadis et al., 2002; Milhaud et al., 2005). Current treatment options for malignant MCA infarction have been immersed in surgical decompression (Huttner et al., 2009; Treadwell et al., 2010). However, there is still debate about the timing and subjects of surgery, and intensive medical treatment including osmotherapy is not sufficient for some patients. TH can be a candidate therapy as an additional treatment strategy, although further investigation for the efficacy of treatment in malignant MCA infarction is needed (Wartenberg KE., 2012). Therefore, the tendency of good clinical outcome and low hemorrhagic transformation represented in the hypothermia group of the malignant MCA infarct group in this study may be very encouraging.
２９
The reasons for the good outcomes of malignant MCA infarction in this study are as follows. First, hypothermia can alleviate reperfusion injury such as hemorrhagic transformation and edema. In patients with substantial ischemic changes (ASPECTS ≤5 on baseline imaging), the functional outcome usually cannot reach the desired level. Additional strategies that emphasize reperfusion injury can be beneficial in malignant MCA infarct trait because reperfusion injury after EVT can be responsible for poor functional recovery. Our results demonstrated the hypothermia group occurred in hemorrhagic transformation less frequent than no hypothermia group, especially in malignant MCA infarct patients. In addition, relative long-term hypothermia therapy (>48 hours) has been performed to prevent rebound cerebral edema.
Second, the critical care might enhance the effectiveness of hypothermia treatment. Previous trials on hypothermia in acute stroke patients usually conducted conscious hypothermia therapy without mechanical ventilation (De Georgia et al., 2004; Polderman et al., 2009). In case of conscious hypothermia, shivering and aspiration can cause various complications. This study is a retrospective study, however, general critical care (sedation with mechanical ventilation, protocolized medical critical care, and timely hemicraniectomy) has been executed. Therefore, patient selection for effective hypothermia and intensive critical care can improve the functional outcome of patients with malignant MCA infarction.
E. Limitations
This study has several limitations. Due to the retrospective nature, the number of hypothermia group was relatively small. We could not investigate the extent of cerebral edema that may reflect reperfusion injury. The inclusion of malignant MCA infarction can be controversial because there are no definitive diagnostic criteria. We classified the patients without DWI lesion within 6 hours as malignant MCA infarct using only baseline severity (NIHSS>20, Item Ia>0). To confirm our perspective of neuroprotection with TH, a prospective study with an appropriate definition of ‘malignant MCA infarction’ should be needed.
Our findings can generalize in applying future neuroprotective agent development.
３０
V.
CONCLUSION
This study shows the effect of hypothermia among the anterior circulation ischemic stroke patients who treated with EVT. The statistical comparison between the hypothermia and no hypothermia groups was impracticable due to the imbalance of baseline characteristics. However, in patients with malignant MCA infarction undergoing EVT, therapeutic hypothermia may reduce the risk of hemorrhagic transformation and lead to an improved clinical outcome. This study suggests that therapeutic hypothermia can be considered as a treatment modality for malignant MCA infarction.
３１
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