How Clot Composition Influences Fibrinolysis in the Acute Phase of Stroke: A Proteomic Study of Cerebral Thrombi.

BACKGROUND: The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA). METHODS: In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FAout) by measuring D-dimer levels at the blood-thrombus interface and inside (FAin) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FAin, and FAout were determined by intravenous thrombolysis-adjusted linear regression. RESULTS: FAout (P<0.0001) and FAin (P=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FAout was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FAout was increased with cardioembolic thrombi (72/104), which are rich in fibrin (P=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (P=0.0139), and hemoglobin level (P=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FAout (P=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FAout was significantly associated with reduced thrombus weight (P=0.0310), increased recanalization rate (P=0.0150), good clinical outcome (P=0.0480), and reduced mortality (P=0.0080). CONCLUSIONS: Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.

Acute and Chronic Kidney Dysfunction and Prognosis following Thrombectomy for Ischemic Stroke.

INTRODUCTION: Patients with chronic kidney disease (CKD) have an increased risk of stroke, and CKD seems associated with worse outcome after a stroke. The main objective of our study RISOTTO was to evaluate the influence of CKD and acute kidney injury (AKI) on the clinical outcome and mortality of ischemic stroke patients after thrombolysis and/or thrombectomy. METHODS: This multicenter cohort study included patients in the acute phase of ischemic stroke due to large artery occlusion managed by thrombectomy. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS). RESULTS: 280 patients were included in the analysis. Fifty-nine patients (22.6%) had CKD. At 3 months, CKD was associated with similar functional prognosis (mRS 3-6: 50.0% vs. 41.7%, p = 0.262) but higher mortality (24.2% versus 9.5%, p = 0.004). In univariate analysis, patients with CKD had a higher burden of white matter hyperintensities (Fazekas score: 1.7 ± 0.8 vs. 1.0 ± 0.8, p = 0.002), lower initial infarct volume with equivalent severity, and lower recanalization success (86.4% vs. 97.0%, p = 0.008) compared to non-CKD patients. Forty-seven patients (20.0%) developed AKI. AKI was associated with poorer 3-month functional outcome (mRS 3-6: 63.8% vs. 49.0%, p = 0.002) and mortality (23.4% versus 7.7%, p = 0.002). In multivariate analysis, AKI appeared as an independent risk factor for poor functional outcome (mRS 3-6: adjOR 2.79 [1.11-7.02], p = 0.029) and mortality (adjOR 2.52 [1.03-6.18], p = 0.043) at 3 months, while CKD was not independently associated with 3-month mortality and poor neurological outcome. CONCLUSIONS: AKI is independently associated with poorer functional outcome and increased mortality at 3 months. CKD was not an independent risk factor for 3-month mortality or poor functional prognosis.

Regional brain glucose metabolism is differentially affected by ketogenic diet: a human semiquantitative positron emission tomography.

PURPOSE: Ketogenic diet (KD) is recommended to avoid intense [18F]FDG myocardial physiologic uptake in PET imaging. Neuroprotective and anti-seizure effects of KD have been suggested, but their mechanisms remain to be elucidated. This [18F]FDG PET study aims to evaluate the effect of KD on glucose brain metabolism. METHOD: Subjects who underwent KD prior to whole-body and brain [18F]FDG PET between January 2019 and December 2020 in our department for suspected endocarditis were retrospectively included. Myocardial glucose suppression (MGS) on whole-body PET was analyzed. Patients with brain abnormalities were excluded. Thirty-four subjects with MGS (mean age: 61.8 ± 17.2 years) were included in the KD population, and 14 subjects without MGS were considered for a partial KD group (mean age: 62.3 ± 15.1 years). Brain SUVmax was first compared between these two KD groups to determine possible global uptake difference. Semiquantitative voxel-based intergroup analyses were secondarily performed to determine possible inter-regional differences by comparing KD groups with and without MGS, separately, to 27 healthy subjects fasting for at least 6 h (mean age of 62.4 ± 10.9 years), and KD groups between them (p-voxel < 0.001, and p-cluster < 0.05, FWE-corrected). RESULTS: A 20% lower brain SUVmax was found in subjects under KD with MGS in comparison to those without MGS (Student's t-test, p = 0.02). Whole-brain voxel-based intergroup analysis revealed that patients under KD with and without MGS had relative hypermetabolism of limbic regions including medial temporal cortices and cerebellum lobes and relative hypometabolism of bilateral posterior regions (occipital), without significant difference between them. CONCLUSION: KD globally reduces brain glucose metabolism but with regional differences, requiring special attention to clinical interpretation. On a pathophysiological perspective, these findings could help understand underlying neurological effects of KD through possible decrease of oxidative stress in posterior regions and functional compensation in the limbic regions.

Diabetes is an Independent Growth Factor of Ischemic Stroke During Reperfusion Phase Leading to Poor Clinical Outcome.

OBJECTIVES: Despite the success of recanalization by bridging therapy, about half of treated stroke patients remain disabled. While numerous reports propose clinical predictors of stroke clinical outcome in this context, we originally aimed to study pre-therapeutic factors influencing infarct growth (IG) and poor clinical outcome in strokes due to large vessel occlusion (LVO) successfully recanalized. MATERIALS AND METHODS: We enrolled 87 consecutive successfully recanalized patients (mTICI: 2b/2c/3) by mechanical thrombectomy (±rt-PA) after stroke due to middle cerebral artery (M1) occlusion within 6 h according to AHA guidelines. IG was defined by subtracting the initial DWI volume to the final 24 h-TDM volume. Statistical associations between poor clinical outcome (mRS≥2), IG and pertinent clinico-radiological variables, were measured using logistic and linear regression models. RESULTS: Among 87 enrolled patients (Age(y): 68.4 ± 17.5; NIHSS: 16.0 ± 5.4), 42/87 (48,28%) patients had a mRS ≥ 2 at 3 months. Diabetic history (OR: 3.70 CI95%[1.03;14.29] and initial NIHSS (/1 point: OR: 1.16 CI95%[1.05;1.27]) were independently associated with poor outcome. IG was significantly higher in stroke patients with poor outcome (+7.57 ± 4.52 vs -7.81 ± 1.67; p = 0.0024). Initial volumes were not significantly different (mRS≥2: 16.18 ± 2.67; mRS[0-1]: 14.70 ± 2.30; p = 0.6771). Explanatory variables of IG in linear regression were diabetic history (ß: 21.26 CI95%[5.43; 37.09]) and NIHSS (ß: 0.83 CI95%[0.02; 1.64]). IG was higher in diabetic stroke patients (23.54 ± 1.43 vs -6.20 ± 9.36; p = 0.0061). CONCLUSIONS: We conclude that diabetes leads to continued IG after complete recanalization, conditioning clinical outcome in LVO strokes successfully recanalized by bridging therapy. We suggest that poor tissular reperfusion by diabetic microangiopathy could explain this result.

Ingested Ketone Ester Leads to a Rapid Rise of Acetyl-CoA and Competes with Glucose Metabolism in the Brain of Non-Fasted Mice.

The role of ketone bodies in the cerebral energy homeostasis of neurological diseases has begun to attract recent attention particularly in acute neurological diseases. In ketogenic therapies, ketosis is achieved by either a ketogenic diet or by the administration of exogenous ketone bodies. The oral ingestion of the ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is a new method to generate rapid and significant ketosis (i.e., above 6 mmol/L) in humans. KE is hydrolyzed into ß-hydroxybutyrate (ßHB) and its precursor 1,3-butanediol. Here, we investigate the effect of oral KE administration (3 mg KE/g of body weight) on brain metabolism of non-fasted mice using liquid chromatography in tandem with mass spectrometry. Ketosis (Cmax = 6.83 ± 0.19 mmol/L) was obtained at Tmax = 30 min after oral KE-gavage. We found that ßHB uptake into the brain strongly correlated with the plasma ßHB concentration and was preferentially distributed in the neocortex. We showed for the first time that oral KE led to an increase of acetyl-CoA and citric cycle intermediates in the brain of non-fasted mice. Furthermore, we found that the increased level of acetyl-CoA inhibited glycolysis by a feedback mechanism and thus competed with glucose under physiological conditions. The brain pharmacodynamics of this oral KE strongly suggest that this agent should be considered for acute neurological diseases.

Anterior Thalamic Stimulation Induced Relapsing Encephalitis.

Deep brain stimulation of the anterior thalamic nucleus is one of the promising therapeutic options for epilepsy. Several studies are still under way to further strengthen and clarify the mechanism, efficacy, and complications. Contrary to hardware-related and operation-related events, the stimulation-related adverse effect is mild, target-dependent, and adjustable. We present a case of relapsing herpes simplex encephalitis (HSE) as a newly reported and potentially fatal stimulation-related adverse effect following stimulation of the anterior thalamic nucleus (ANT-DBS) accompanied by fever, confusion, and cognitive impairment in a 32-year-old epileptic patient with a history of herpes meningoencephalitis 31 years earlier. The T2-weighted/FLAIR high-signal intensity in the temporal lobe developed at a "distance" from the stimulation target. The positive polymerase chain reaction of herpes virus deoxyribonucleic acid in the cerebrospinal fluid confirmed the diagnosis. The condition improved partially on acyclovir and stimulation stopped. Seizures disappeared and then returned after few months. The unique case report presents a rationale for considering history of herpes encephalitis as a relative contraindication for ANT-DBS, and HSE relapse should be suspected in patients with post-stimulation fever and/or altered consciousness.

Hypoperfusion of the thalamus is associated with disability in relapsing remitting multiple sclerosis.

BACKGROUND: While gray matter (GM) perfusion abnormalities have been evidenced in multiple sclerosis (MS) patients, the relationships with disability still remain unclear. Considering that atrophy is known to impact on perfusion, we aimed to assess perfusion abnormalities in GM of MS patients, outside atrophic regions and investigate relationships with disability. METHODS: Brain perfusion of 23 relapsing remitting MS patients and 16 matched healthy subjects were assessed at 3T using the pseudo-continuous arterial spin labeling magnetic resonance imaging technique. In order to locate potential GM perfusion abnormalities in regions spared by atrophy, we combined voxelwise comparisons of GM cerebral blood flow (CBF) maps (cortex and deep GM) (P<0.005, FWE-corrected) and voxel-based-morphometry analysis (P<0.005, FDR-corrected) to exclude atrophic regions. Disability was assessed using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite score (MSFC). RESULTS: In patients, significant GM hypoperfusion outside atrophic regions was depicted only in bilateral thalami. No other cluster was found to be hypoperfused compared to controls. Perfusion of thalami was correlated to MSFC (P=0.011, rho=0.523). A trend of correlation was found between perfusion of thalami and EDSS (P=0.061, rho=-0.396). CONCLUSION: In relapsing remitting MS, perfusion abnormalities in thalamic regions contribute to disability. These findings suggest that functional impairments of thalami, representing a major brain hub, may disturb various cerebral functions even before structural damage.

Neuroprotective effects of lactate and ketone bodies in acute brain injury.

The goal of neurocritical care is to prevent and reverse the pathologic cascades of secondary brain injury by optimizing cerebral blood flow, oxygen supply and substrate delivery. While glucose is an essential energetic substrate for the brain, we frequently observe a strong decrease in glucose delivery and/or a glucose metabolic dysregulation following acute brain injury. In parallel, during the last decades, lactate and ketone bodies have been identified as potential alternative fuels to provide energy to the brain, both under physiological conditions and in case of glucose shortage. They are now viewed as integral parts of brain metabolism. In addition to their energetic role, experimental evidence also supports their neuroprotective properties after acute brain injury, regulating in particular intracranial pressure control, decreasing ischemic volume, and leading to an improvement in cognitive functions as well as survival. In this review, we present preclinical and clinical evidence exploring the mechanisms underlying their neuroprotective effects and identify research priorities for promoting lactate and ketone bodies use in brain injury.

Symptomatic Carotid Free-Floating Thrombus: About Management of 50 Cases in a Referral Neurovascular Center.

BACKGROUND: Carotid free-floating thrombus (CFFT) is an uncommon disorder. The aim of this study was to describe a French cohort of CFFT patients. METHODS: We conducted a retrospective monocentric study from a Stroke Center among patients admitted for stroke with CFFT. RESULTS: Between January 2017 to December 2019, 2038 ischemic strokes were recorded. A total of 50 patients with CFFT were consecutively included (32 men/18 women). The mean age was 58.2 years (±11.7). Their etiologies were atheroma (46%), carotid dissection and web (20%), hypercoagulability disorders (16%) and arrhythmia (10%). Exclusive medical management was performed in 38 patients (76%): 29 (59.2%) were anticoagulated and 9 (18.4%) received antiplatelets alone in the first week. Surgical intervention was performed in the first 30 days for 11 patients (22%). The main surgical indication was a residual carotid stenosis over 70%. Only three patients had a recurrent stroke in the medical group with anticoagulants. No patients in the antiplatelet group or the surgical group had a recurrent stroke. CONCLUSIONS: Our study summarized a large cohort of 50 patients with CFFT. This diagnosis implies the need to search for a local arterial disease and to screen for hypercoagulability states. An initial medical strategy followed by a delayed carotid surgery if the follow-up imaging shows a residual stenosis appears to be safe.

Atrial Fibrillation Detected by Implantable Monitor in Embolic Stroke of Undetermined Source: A New Clinical Entity.

BACKGROUND: High incidence of covert paroxysmal atrial fibrillation (CPAF) detected by an implantable cardiac monitor (ICM) is expected in embolic stroke of undetermined source (ESUS) patients. This study aimed to determine the CPAF rate in an ESUS cohort using ICMs and compare stroke characteristics of patients with CPAF to those with known or inpatient-diagnosed AF (KIDAF). METHODS: ESUS patients with ICMs were enrolled. ESUS diagnosis was defined as a non-lacunar stroke in the absence of symptomatic atherosclerotic stenosis (≥50%), no major-risk cardioembolic source, and no other specific cause. ESUS characteristics of patients with CPAF were compared to ESUS patients without CPAF and to KIDAF stroke patients. RESULTS: During the median follow-up of 476 (371-615) days, CPAF was newly detected in 38/163 (23.31%) patients within 236 (115.50-510.75) days after the stroke. CPAF was independently associated to older age, coronaropathy, left atrial dilation, and atrial hyperexcitability, but not to stroke severity. Compared to KIDAF strokes, ESUS with CPAF had lower rates of proximal occlusion leading to milder clinical severity (NIHSS: 3.00 (1.00-8.25) vs. 14.50 (6.00-21.00)). CONCLUSIONS: Our study revealed a high proportion of CPAF in ESUS. We highlight that CPAF is a distinct clinical entity compared to KIDAF based on differences in stroke characteristics and AF diagnosis temporality.

Stroke in a young patient treated by alteplase heralding an acquired thrombotic thrombocytopenic purpura.

BACKGROUND AND PURPOSE: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disorder characterized by thrombocytopenia and fluctuating neurological symptoms due to microinfarcts. In rare cases, large cerebral arteries can be occluded. SUMMARY OF THE CASE: We report on a 30-year-old woman with a first-ever acute stroke related to a right proximal MCA M1 occlusion. Platelet count was normal at admission and progressively decreased 6 days after intravenous thrombolysis with the occurrence of a hemolytic anemia with schistocytes. Most biological anomalies reversed after plasma exchange. No hemorrhagic complication occurred. Diagnosis of initial TTP was confirmed by low ADAMTS13 activity and positivity of anti-ADAMTS13 antibody. CONCLUSION: This observation highlights the fact that even if platelet count and hemoglobin rate are normal in the beginning, an acute ischemic stroke in a young patient can be related to TTP. Faced with subsequent thrombopenia, practitioners should be aware of acquired TTP, and, thus, schistocytes, haptoglobin, and LDH assays should be performed. Early diagnosis is paramount to start the life-saving plasma exchanges.

Stroke after spontaneous intracranial hypotension: Not a single mechanism. Case report and review of literature.

Spontaneous intracranial hypotension (SIH) is a rare syndrome, typically manifests as orthostatic headache. Sometimes considered asbenignillness, neurological complications are well described, in particular subdural hematoma and cerebral venous sinus thrombosis. Brain infarction as complication of SIH is rarely reported. The main mechanism supported in the literature is the stretching of arteries due to the sagging of the brain. We report a case of SIH followed with brain infarction, with a distinct presentation from previous literature, suggesting a different mechanism. A 35 year-old had severe orthostatic headache, responsible for prolonged bed rest. One month later, he had acute left hemiparesis secondary to stroke and right posterior cerebral artery occlusion. Stroke MRI showed arguments for intracranial hypotension (thickened meninges). He was successfully treated with intravenous rtPA thrombolysis. Headache were resolved after an epidural blood patch. A patent foramen ovale was detected. Clinical features of this description were compared with previous literature. This case suggest a different mechanism for cerebral infarction after intracranial hypotension. In case of prolonged lying down due to intracranial hypotension, the presence of patent foramen ovale could be a risk factor for embolic stroke.

Metabolome of Cerebral Thrombi Reveals an Association between High Glycemia at Stroke Onset and Good Clinical Outcome.

Despite the fact that glucose is the main fuel of the brain, hyperglycemia at hospital admission is generally associated with a poor functional outcome in stroke patients. This paradox may be explained by the lack of information about the blood glucose level at stroke onset. Here, we analyzed the metabolome of blood cells entrapped in cerebral thrombi to gain insight into their metabolism at stroke onset. Fourty-one consecutive stroke patients completely recanalized by mechanical thrombectomy within 6 h were included. The metabolome of retrieved thrombi was analyzed by liquid chromatography tandem with mass spectrometry. Discriminant Analysis (sparse Partial Least Squares Discriminant Analysis (sPLS-DA)) was performed to identify classification models and significant associated features of favorable clinical outcome at 3 months (modified Rankin Scale (mRS) < 2). sPLS-DA of the metabolomes of cerebral thrombi discriminated between stroke patients with a favorable or poor clinical outcome (Area Under the Curve (AUC) = 0.992 (0.931-1)). In addition, our results revealed that high sorbitol and glucose levels in the thrombi positively correlated with favorable clinical outcomes. Sorbitol, a short-term glycemic index reflecting a high blood glucose level at stroke onset, was found to be an independent predictor of good outcome (AUC = 0.908 (0.807-0.995)). This study demonstrates that a high blood glucose level at stroke onset is beneficial to the clinical outcome of the patient.

Effect of hyperglycemia on stroke outcome is not homogeneous to all patients treated with mechanical thrombectomy.

OBJECTIVES: Admission hyperglycemia is a penumbra-modifying factor that is associated with poor functional outcome in acute ischemic stroke (AIS) patients treated with intravenous rt-PA and/or mechanical thrombectomy (MT). Insulin therapy has failed to demonstrate a clinical benefit and the question of the patient selection remains under debate. We assessed the relationship between admission glycemia (AG) and functional outcome in AIS patients treated by MT according to both penumbra characteristics and reperfusion status. PATIENTS AND METHODS: We performed a retrospective analysis of a multi-center registry of consecutive AIS (NIHSS ≥ 10) due to middle cerebral artery occlusion treated by MT (± tissue Plasminogen Activator (tPA)). To evaluate the association between AG and the 3-month functional outcome (modified Rankin Scale (mRS) ≤2), univariable and multivariable analyses were used. Subgroup analyses were performed according to both clinical-ASPECTS Mismatch (CAM2) and the complete recanalization (CR) status defined by a mTICI scale (modified Thrombolysis in Cerebral Infarction) 2b/3. RESULTS: 216 AIS patients were included (Median Age: 68.43[58.12-77.95], median NIHSS: 18[15-21]). 104/216 (48.15%) patients had mRS≤2 at 3 months. AG was an independent predictor of functional outcome (/1 g/L OR: 0.10[0.03-0.37]) after adjusting for potential cofounders. Among subgroups formed by combining CAM2 and CR, AG was found to be predictor of functional outcome only in CAM2+/CR+ and specifically when recanalization was early. CONCLUSION: This study highlights the fact that the relationship between AG and prognosis is not homogeneous for all patients and indicates that AG has a deleterious effect on the ischemic penumbra, thus explaining its statistical association with functional outcome. Stroke neuroprotection by targeting hyperglycemia should be considered in acute stroke patients with mismatch and early complete recanalization. More prospective randomized trials are needed to generalize the conclusions.

Intracranial haemorrhage in infective endocarditis.

BACKGROUND: Although intracranial cerebral haemorrhage (ICH) complicating infective endocarditis (IE) is a critical clinical issue, its characteristics, impact, and prognosis remain poorly known. AIMS: To assess the incidence, mechanisms, risk factors and prognosis of ICH complicating left-sided IE. METHODS: In this single-centre study, 963 patients with possible or definite left-sided IE were included from January 2000 to December 2015. RESULTS: Sixty-eight (7%) patients had an ICH (mean age 57±13 years; 75% male). ICH was classified into three groups according to mechanism: ruptured mycotic aneurysm (n=22; 32%); haemorrhage after ischaemic stroke (n=27; 40%); and undetermined aetiology (n=19; 28%). Five variables were independently associated with ICH: platelet count<150×109/L (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.01-5.4; P=0.049); severe valve regurgitation (OR 3.2, 95% CI 1.3-7.6; P=0.008); ischaemic stroke (OR 4.2, 95% CI 1.9-9.4; P<0.001); other symptomatic systemic embolism (OR 14.1, 95% CI 5.1-38.9; P<0.001); and presence of mycotic aneurysm (OR 100.2, 95% CI 29.2-343.7; P<0.001). Overall, 237 (24.6%) patients died within 2.3 (0.7-10.4) months of follow-up. ICH was not associated with increased mortality (P not significant). However, the 1-year mortality rate differed according to ICH mechanism: 14%, 15% and 45% in patients with ruptured mycotic aneurysm, haemorrhage after ischaemic stroke and undetermined aetiology, respectively (P=0.03). In patients with an ICH, mortality was higher in non-operated versus operated patients when cardiac surgery was indicated (P=0.005). No operated patient had neurological deterioration. CONCLUSIONS: ICH is a common complication of left-sided IE. The impact on prognosis is dependent on mechanism (haemorrhage of undetermined aetiology). We observed a higher mortality rate in patients who had conservative treatment when cardiac surgery was indicated compared with in those who underwent cardiac surgery.

Association of Posterior Reversible Encephalopathy Syndrome and Transient Apical Ballooning Syndrome (Takotsubo): First Case Report of a Man and Review of the Literature.

INTRODUCTION: An association of posterior reversible encephalopathy syndrome (PRES) and takotsubo is rare. We present the first case of a male patient. CASE REPORT: A 69-year-old man presented to the hospital in a persistent comatose state following a generalized tonic-clonic seizure with high blood pressure. The electrocardiogram revealed transient left bundle branch block. Troponin and BNP were elevated. Cardiac ultrasound showed large apical akinesia with altered left ventricular ejection fraction, and the left ventriculogram showed characteristic regional wall motion abnormalities involving the mid and apical segments. Brain MRI showed bilateral, cortical, and subcortical vasogenic edema predominant in the posterior right hemisphere. The lumbar puncture and cerebral angiography were normal. Paraclinical abnormalities were reversible within 2 weeks with a clinical recovery in 3 months, confirming the takotsubo and the PRES diagnoses. DISCUSSION: Several theories hypothesize the underlying pathophysiology of takotsubo or PRES. Circulating catecholamines are up to 3 times higher in patients with takotsubo causing impaired microcirculation and apical hypokinesia. An association of both takotsubo and asthma crisis and PRES and asthma crisis underlines the role of catecholamines in the occurrence of these disorders. CONCLUSION: Early recognition of this rare association, in which heart and neurological damage may require rapid intensive care support, is needed.