Advances in the Diagnosis and Treatment of Pediatric Arterial Ischemic Stroke.

Though rare, stroke in infants and children is an important cause of mortality and chronic morbidity in the pediatric population. Neuroimaging advances and implementation of pediatric stroke care protocols have led to the ability to rapidly diagnose stroke and in many cases determine the stroke etiology. Though data on efficacy of hyperacute therapies, such as intravenous thrombolysis and mechanical thrombectomy, in pediatric stroke are limited, feasibility and safety data are mounting and support careful consideration of these treatments for childhood stroke. Recent therapeutic advances allow for targeted stroke prevention efforts in high-risk conditions, such as moyamoya, sickle cell disease, cardiac disease, and genetic disorders. Despite these exciting advances, important knowledge gaps persist, including optimal dosing and type of thrombolytic agents, inclusion criteria for mechanical thrombectomy, the role of immunomodulatory therapies for focal cerebral arteriopathy, optimal long-term antithrombotic strategies, the role of patent foramen ovale closure in pediatric stroke, and optimal rehabilitation strategies after stroke of the developing brain.

[Evaluation of intravascular therapy for cerebral ischemic tandem stenosis].

Objective: To investigate the efficacy and the safety of intravascular therapy for cerebrovascular ischemic tandem stenosis. Methods: Clinical data of 35 patients with symptomatic anterior circulation and posterior circulation tandem stenosis who received intravascular therapy for two sites of stenosis at the same time at Department of Neurosurgery of Peking University First Hospital from January 2013 to December 2018 were analyzed retrospectively. There were 27 males and 8 females,aged (65.6±9.4)years (range:47 to 81 years).There were 14 cases of anterior circulation tandem stenosis and 21 of posterior circulation tandem stenosis.The medical records were collected with emphasis on postoperative symptoms,imaging manifestations and modified Rankin scale(mRS) scores. Results: Sixty-eight stents were implants in to 35 patients,including 49 extracranial implants and 19 intracranial implants.The surgical success rate was 100%.The perioperative death rate was 0,and 1 patient(1/35,2.9%) had cerebral hemorrhage.All patients were followed up for 18 months.During 3 to 12 months after the intervention,1 case(1/35,2.9%) had stent restenosis,and 4 cases(4/35,11.4%) had persisted symptoms such as dizziness and weakness in limbs.All patients'mRS scores were ≤2. No new stroke occurred. During 12 to 18 months after the intervention,3 cases had in-stent restenosis,increasing the rate to 11.4% (4/35). The mRS scores of 32 patients(32/35,91.4%) were ≤2. Conclusion: Intravascular therapy for patients with symptomatic tandem stenosis is a feasible and safe procedure with good short-term outcomes.

Management of Intracranial Stenotic Disease in Cancer Patients Treated With Vasotoxic Agents.

OBJECTIVE: To summarize the characteristics of and therapeutic options for cancer patients whose treatments may be vasotoxic and cause intracranial arterial stenotic disease and stroke. METHODS: We describe 3 patients with symptomatic cerebrovascular pathology that were being actively treated for cancer. RESULTS: Two of the patients were being treated with tyrosine kinase inhibitors (TKIs); and the third was being treated with 2 monoclonal antibodies, one of which was targeting an endothelial growth factor. These agents have been associated with vascular adverse events. Surgical revascularization was done in the first 2 patients, as they were suffering from cerebral ischemia. The third patient had suffered a significant brain hemorrhage, and therapeutic options were limited. In the first 2 patients, treatments also included antiplatelet agents and stopping/changing the TKI. In one of these patients we demonstrated regression of arterial stenosis after changing the TKI. CONCLUSIONS: Possibilities for treatment in this population, beyond the usual medical and surgical administrations, may include stopping or changing cancer drugs that may be related to the development of arterial pathology. Collaboration with oncologists is essential in this subset of patients. While aware of the potential for vascular toxicity, oncologists are often not fully appreciative of the fact that their therapeutic agents can cause stroke.

A Follow-up Study of Cerebral Microbleeds in Patients Who Received Stents for Symptomatic Cerebral Artery Stenosis.

BACKGROUND: The aims of this study were to explore (i) the dynamic changes in cerebral microbleeds (CMBs) in patients with symptomatic cerebral artery stenosis who received endovascular stent-assisted angioplasty and (ii) the risk factors associated with the new incidence of CMBs as well as whether CMBs increased the risk of vascular events in these patients. METHODS: Clinical information and magnetic resonance images were collected on admission and 3 months after endovascular stent-assisted angioplasty. Based on susceptibility-weighted imaging, the patients were divided into groups with or without newly developed CMBs, and between-group differences in risk factors were compared. We also compared whether CMBs increased the risk of vascular events among those patients. RESULTS: Seventy-three patients completed the relevant follow-up examinations. After an average follow-up period of 109 days, 7 (9.6%) patients showed new CMBs. A univariate analysis showed that the number of lacunar infarcts and the increase in systolic blood pressure were higher in patients with new CMBs than in those without new CMBs, and these differences were significant (P = 0.034, P = 0.001). Increased systolic blood pressure was an independent risk factor for developing new CMBs (P = 0.017). CONCLUSIONS: CMBs may be a continuously progressing cerebral small-vessel disease. The newly developed CMBs in patients with intracranial and/or extracranial stents were associated with increased systolic blood pressure but not with the number of baseline CMBs.

Recent developments and new frontiers in childhood arterial ischemic stroke.

This review will discuss important developments in childhood arterial ischemic stroke over the past decade, focusing on improved understanding of the causes, consequences, and targets for intervention. Risk factors for childhood arterial ischemic stroke are different to adults. Infections, particularly herpes group viruses, are important precipitants for stroke. Non-atherosclerotic arteriopathies are the most common cause of childhood arterial ischemic stroke and an important predictor of recurrent events. Recent advances include the identification of serum biomarkers for inflammation and endothelial injury, and imaging biomarkers to monitor for vascular progression. Multicenter trials of immunotherapies in focal cerebral arteriopathies are currently in development. Recognition of clinical and radiological phenotypic patterns has facilitated the discovery of multisystem disorders associated with arterial ischemic stroke including ACTA2 arteriopathy and adenosine deaminase 2 deficiency. Identification of these Mendelian disorders provide insights into genetic mechanisms of disease and have implications for medical and surgical management. In contrast to adults, there are long diagnostic delays in childhood arterial ischemic stroke. Refinement of pediatric Code Stroke protocols and clinical decision support tools are essential to improve diagnostic certainty and improve access to reperfusion therapies. Children do not recover better than adults following arterial ischemic stroke, with more than half of survivors having long-term impairments. The physical, cognitive, and behavioral consequences of childhood arterial ischemic stroke are increasingly reported but further research is required to understand their impact on participation, quality of life, psychosocial, and family functioning. Longitudinal studies and the use of advanced imaging techniques, to understand neurobiological correlates of functional reorganization, are essential to developing targeted intervention strategies to facilitate recovery.

Treatment strategies for traumatic cervico-cranial pseudoaneurysms: A single institution experience.

AIM: Limited clinical and angiographic data exists for patients with traumatic cervico-cerebral pseudoaneurysms. In this paper, we present our limited experience with various management strategies for traumatic cervico-cranial pseudoaneurysms. MATERIALS AND METHODS: We retrospectively analyzed 37 consecutive cases of traumatic pseudoaneurysms involving the cervico-cranial or the cerebral arteries diagnosed at our center from September 2009 to December 2014. The demographic data, etiology, clinical presentation, lesion location, treatment modality, and follow-up outcomes of these patients were reviewed. Among these 37 patients, 5 patients were treated by surgery, while 29 patients were treated by the endovascular approach and 3 received conservative treatment. RESULTS: During the study period, 42 pseudoaneurysms were identified in 37 patients with a history of head or neck injury. Five patients underwent surgical exploration of the lesion with an uneventful postoperative course. Twenty-nine patients were treated by endovascular interventions with various embolization materials including coils, stents, detachable balloons, liquid embolic agents, and a combination of these agents. The angiographic follow-up imaging demonstrated complete exclusion of the aneurysm from the circulation with the patient being free from any additional neurological deficits. CONCLUSION: Proper selection of an appropriate approach is essential to address the management of traumatic cervico-cerebral pseudoaneurysms. The treatment of traumatic cervico-cerebral pseudoaneurysms should be selected according to the location and the clinical features of the pseudoaneurysms. The endovascular treatment is a safe and effective modality and should be the first-line choice for treatment of traumatic pseudoaneurysms.

Traumatic Anterior Cerebral Artery Pseudoaneurysmal Epistaxis.

BACKGROUND: Pseudoaneurysmal epistaxis is a rare but emergent condition. We report a case of traumatic anterior cerebral artery pseudoaneurysmal epistaxis and review the published literature. CASE DESCRIPTION: A 49-year-old man sustained severe head trauma. He was diagnosed with multiple skull bone fractures, left subdural hematoma, subarachnoid hemorrhage, pneumocephalus, and right frontal hematoma. Subdural hematoma evacuation was done at a local hospital. In the following months, he experienced repeated epistaxis that required nasal packing to stop the bleeding. Digital subtraction angiography showed an anterior cerebral artery pseudoaneurysm protruding into the posterior ethmoid sinus. Embolization of the aneurysm was performed with microcoils, and the parent artery was occluded by thrombosis. The patient presented 1 month later with another epistaxis episode. Digital subtraction angiography showed recanalization of the parent artery and recurrence of the aneurysm. The parent artery was occluded for the second time with coils and Onyx embolic agent. CONCLUSIONS: Pseudoaneurysmal epistaxis is rare, and this is the first report of an anterior cerebral artery pseudoaneurysm that manifested with epistaxis. Endovascular intervention has become the first choice of treatment for this disease. The high recurrence rate is the main disadvantage of endovascular intervention. Aneurysm trapping with bypass surgery is another treatment option.

Treatment of distal anterior cerebral artery aneurysms with the Pipeline Embolization Device.

Aneurysms of the anterior cerebral artery (ACA) located distal to the anterior communicating artery complex (ACOM) remain challenging to treat with surgical clip reconstruction as well as with endovascular coil-embolization strategies. We have treated five complex geometry distal ACA aneurysms with endoluminal reconstruction using the Pipeline Embolization Device (PED). Two aneurysms were of the dysplastic fusiform type. Three aneurysms were of complex saccular configuration. Three aneurysms were treated electively at the outset with PED. One patient had previously undergone aborted clip reconstruction, and one was treated for recurrent aneurysm growth after coil embolization. The mean diameter of the ACA in this cohort was 1.96mm proximal to the aneurysm and 1.79mm distal to the aneurysmal segment. A single PED of 2.5mm inner diameter was the sole treatment in four cases. Two PEDs, telescopically overlapped across the aneurysm, were used in the remaining case. All devices were deployed successfully. No parent artery occlusion or stenosis was observed. In all cases an associated branch vessel arising from the vicinity of the aneurysm or incorporated into its neck was covered by the endoluminal construct. At follow-up angiography, robust antegrade flow was maintained in the jailed branch. One patient experienced asymptomatic, delayed occlusion of the jailed branch. Complete aneurysm occlusion was seen in all patients. We confirm that PED can be deployed in parent vessels smaller than 2mm diameter, and that endoluminal reconstruction with the PED may be a safe and effective treatment alternative for selected distal ACA aneurysms.

[Consciousness Impairment and Left Hemiparesis due to Contrast Medium in the Coil Embolization of Unruptured Large Right Middle Cerebral Artery Aneurysm: A Case Report].

Neurological deficits following coil embolization of anterior circulation aneurysms due to the toxicity of contrast medium are rare. Here, we describe a patient with mild consciousness impairment and left hemiparesis following coil embolization of a large right middle cerebral artery aneurysm without evidence of ischemia or hemorrhage, who recovered completely with conservative treatment. The patient's clinical course and radiological findings led us to conclude that the neurological deficits were due to the toxic effect of contrast medium used during the coil embolization.

Thrombectomy in patients with large cerebral artery occlusion: a single-center experience with a new stent retriever.

INTRODUCTION: The Trevo device, a new stent retriever, may be utilized in patients with large cerebral artery occlusion. METHODS: Fifty patients with large cerebral artery occlusion and treated with the Trevo device were analyzed. Patients may have received intravenous thrombolysis as a bridging concept in addition to thrombectomy. Outcome and recanalization parameters were documented using the National Institutes of Health Scale, the modified Ranking Scale (mRS) and Thrombolysis in Cerebral Infarction (TICI) score. RESULTS: In all, 82% (95% confidence interval [CI]: 69%-91%) were documented with TICI 2b and 3. Good clinical outcome after 90 days (mRS ≤ 2) was assessed in 61% (95% CI: 46%-75%). Symptomatic intracerebral hemorrhage occurred in 6 patients (12%, 95% CI: 1%-17%). The overall mortality rate was 14% (95% CI: 6%-27%). CONCLUSION: Thrombectomy with the new stent retriever device is feasible and effective and has an acceptable risk of intra-cerebral hemorrhage even in combination with pharmacological revascularization techniques.

Moyamoya disease with posterior communicating artery aneurysm: a case report.

In moyamoya disease (MMD), subsequent aneurysm in the proximal part of the posterior communicating artery (PcomA) is extremely rare. We report the case of a middle-aged female patient with MMD, who presented with a ruptured wide-necked aneurysm at the proximal part of the developed PcomA that converged with the posterior cerebral artery (PCA) and supplied the distal area. Endovascular treatment was performed, but the stent-assisted coil embolization resulted in occlusion of the internal carotid artery (ICA) above the ophthalmic artery and PcomA. Due to good compensatory collateral circulation, the patient was improved after surgery and had no complications. One-year followup DSA did not show recurrence of the aneurysm. The right ICA was still embolized, but with good compensatory collateral circulation. We conclude that, for an MMD patient with an aneurysm at the proximal part of the developed PcomA, if the ICA and PcomA are accidentally occluded, then the patient may still have a good prognosis due to sufficient collateral blood circulation.

Direct thrombus aspiration using the Penumbra system for the treatment of pediatric intracranial dissection.

We describe a case of a 15-year-old girl who developed a spontaneous intracranial arterial dissection with distal middle cerebral artery (MCA) occlusions. From the digital subtraction angiography provided, the dissection flap appeared to originate at the internal carotid artery terminus with extension into the right M1 segment and occluding the right anterior cerebral artery, A1 segment. CT perfusion study showed salvageable tissue in the posterior MCA territory, including the motor cortex. In order to avoid further injury to the dissection, clot retrieval systems were not a treatment option. We therefore performed selective thrombus aspiration with the Penumbra system for the occluded central and precentral arteries distal to the non-occlusive dissecting lesion. Sufficient recanalization was achieved and the patient made a marked recovery. Although mechanical thrombectomy with the use of retrieval intracranial stent systems has demonstrated satisfactory recanalization rates, the aspiration methodology remains useful for patients with an accompanying proximal vascular lesion.

Factors associated with favorable response to hyperbaric oxygen therapy among patients presenting with iatrogenic cerebral arterial gas embolism.

BACKGROUND: Iatrogenic cerebral arterial gas embolism (CAGE) is an uncommon but potentially a fatal condition. Hyperbaric oxygen (HBO2) therapy is the only definitive treatment for patients with CAGE presenting with acute neurologic deficits. METHODS: We reviewed medical records and neuroimaging of consecutive CAGE patients treated with HBO2 at a state referral hyperbaric facility over a 22-year period. We analyzed the effect of demographics, source of intra-arterial gas, signs and symptoms, results of imaging studies, time between event and HBO2 treatment, and response to HBO2 treatment in 36 consecutive patients. Favorable outcome was defined by complete resolution or improvement of CAGE signs and symptoms at 24 h after HBO2 treatment. Unfavorable outcome was defined by unchanged or worsened neurologic signs and symptoms or in hospital death. RESULTS: A total of 26 (72%) of the 36 patients had favorable outcome. Patients with favorable outcome were younger compared to those with unfavorable outcome (mean age [years, SD] 44.7 ± 17.8 vs. 58.1 ± 24.1, p = 0.08). Cardiopulmonary symptoms were significantly more common in CAGE related to venous source of gas compared to arterial source (p = 0.024) but did not influence the rate of favorable outcomes. Adjusted multivariate analysis demonstrated that time from event to HBO2 ≤ 6 h (positively) and the presence of infarct/edema on head computerized tomography (CT)/magnetic resonance imaging (MRI) before HBO2 (negatively) were independent predictors of favorable outcome at 24 h after HBO2 treatment [odds ratio (OR) 9.08 confidence interval (CI) (1.13-72.69), p = 0.0376, and (OR) 0.034 (CI) (0.002-0.58), p = 0.0200, respectively]. Two of the 36 patients were treated with thrombolytics because of acute focal deficits and suspected ischemia-one with intravenous and the second with intra-arterial thrombolysis. The latter patient developed fatal intracerebral hemorrhage. CONCLUSIONS: A high proportion of CAGE patients treated with HBO2 had favorable outcomes. Time-to-HBO2 ≤ 6 h increased the odds of favorable outcome, whereas the presence of infarct/edema on CT/MRI scan before HBO2 reduced the odds of a favorable outcome. Timely diagnosis and differentiation from thrombo-embolic ischemic events appears to be an important determinant of successful HBO2 treatment.

Cerebral tissue hemoglobin saturation in children with sickle cell disease.

BACKGROUND: Desaturation of hemoglobin (Hb) in cerebral tissue, a physiologic marker of brain vulnerable to ischemic injury, can be detected non-invasively by transcranial oximetry. Absolute cerebral oximetry has not been studied in sickle cell disease (SCD), a group at very high risk of cerebral infarction in whom prevention of brain injury is key. PROCEDURE: We measured absolute Hb saturation in cerebral tissue (S(CT)O(2)) in children with SCD using near-infrared spectrophotometry and investigated the contributions of peripheral Hb saturation (S(P)O(2)), hematologic measures, cerebral arterial blood flow velocity, and cerebral arterial stenosis to S(CT)O(2). We also assessed the effects of transfusion. RESULTS: We studied 149 children with SCD (112 HbSS/Sß(0); 37 HbSC/Sß(+)). S(CT)O(2) was abnormally low in 75% of HbSS/Sß(0) and 35% of HbSC/Sß(+) patients. S(CT)O(2) (mean ± SD) was 53.2 ± 14.2 in HbSS/Sß(0) and 66.1 ± 9.2% in SC/Sß(+) patients. S(CT)O(2) correlated with age, sex, Hb concentration, reticulocytes, Hb F, and S(P)O(2), but not transcranial Doppler arterial blood flow velocities as continuous measures. In multivariable models, S(P)O(2), Hb concentration, and age were significant independent determinants of S(CT)O(2). Cerebral vasculopathy was associated with ipsilateral cerebral desaturation. Transfusion increased S(CT)O(2) and minimized the inter-hemispheric differences in S(CT)O(2) due to vasculopathy. CONCLUSIONS: Cerebral desaturation, a physiologic marker of at-risk brain, is common in SCD, more severe in HbSS/Sß(0) patients, and associated with peripheral desaturation, more severe anemia, and increasing age. Cerebral oximetry has the potential to improve the identification of children with SCD at highest risk of neurologic injury and possibly serve as a physiologic guide for neuroprotective therapy.

Cerebral arteritis with extremely late onset secondary to bacterial meningitis - case report - .

A 59-year-old woman presented with bacterial meningitis causing arterial narrowing in the very late stage. She initially underwent transsphenoidal surgery for massive non-functioning pituitary adenoma resulting in gross total removal. The postoperative course was uneventful, and she was discharged 12 days after surgery. Fourteen months later, she presented with bacterial meningitis due to streptococcus. Administration of multiple antibiotics resulted in normalization of cerebrospinal fluid findings. Forty days after meningitis onset, she suddenly suffered motor weakness of the right extremities. Magnetic resonance (MR) angiography revealed multiple intracranial arterial narrowings. Despite intensive treatment, no improvement of arterial narrowing was seen, and she suffered cerebral infarction. Six months after the onset of meningitis, MR angiography still showed multiple arterial narrowings, and MR plaque imaging of the stenotic vessel disclosed thickened arterial wall. This case illustrates the complex time course of arteritis caused by severe bacterial meningitis, and the intractability to treatment.

Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort.

Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Créteil newborn SCA cohort (n = 217 SS/Sß(0)), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigen-genoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L × 10(9)/L increase, 95% CI 1.000-1.006; P = .04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P = .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention.

[Segmental mediolytic arteriopathy (SMA) of central, visceral and peripheral vessels]. / Segmental mediolytische Arteriopathie der zentralen, viszeralen und peripheren Gefässe.

HISTORY AND CLINICAL FINDINGS: A 27-year-old man had been admitted to hospital with acute neurological defects involving his legs and urinary system. An intervertebral disk was removed surgically, because a herniation had been suspected. But symptoms increased postoperatively. Further imaging showed a ruptured aneurysm of the internal iliac artery which was treated with coil embolization. INVESTIGATIONS: Further diagnostic tests excluded hematological, rheumatic and endocrinological causes for the development of the aneurysm. Genetic differentiation was normal. Imaging then demonstrated "string of beads" small aneurysms of intra- and extracerebral, renal, visceral and peripheral arteries. TREATMENT AND COURSE: During the past three years the patient had repeated ruptures of the intra-abdominal arterial aneurysms for which coil embolization and bypass grafting were performed, also to prevent further ruptures. CONCLUSIONS: Segmental mediolytic arteriopathy is a rare condition requiring careful imaging and histological tests for its diagnosis and acute surgical treatment.

A 62-year-old woman with cerebral artery air embolism during commercial air travel.

OBJECTIVE: Air embolism to the cerebral artery circulation is a rare complication previously associated with surgery, scuba-diving, induced abortion, angiography, and pneumothorax. However, air embolism secondary to a ruptured air bulla during commercial air travel has rarely been reported. METHODS: We report a patient who became unconsciousness 30 minutes after her plane took off. RESULTS: The patient was found to have an acute brain infarct in a watershed distribution secondary to multiple, bilateral, intraparenchymal air bubbles. Further investigation revealed a large lung bulla with an air-fluid level. CONCLUSION: Air embolism was due to rupture of the lung bulla into the pulmonary venous outflow. Whether the rupture was spontaneous or due to a stretch injury from a change of air pressure resulting in pulmonary barotrauma occurring during commercial air travel is uncertain.

Childhood and teenage stroke.

OBJECTIVE: The purpose of this manuscript is to review the various etiologies and to discuss the therapeutic issues in childhood stroke. METHODS: A PubMed search of literature pertaining to childhood stroke was conducted from 1983 to 2008 using specific key search words pertinent to cerebrovascular disorders in childhood. RESULTS: The analysis of the multiple causes of childhood stroke including arterial ischemic strokes and cerebral venous thrombosis was presented. Current therapy and outcome data in childhood stroke are also discussed throughout the length of the article. CONCLUSIONS: With increasing vigilance among physicians and improved neuroimaging modalities, the diagnosis of childhood stroke is now made earlier, with increasing frequency and greater accuracy. However, larger and well-controlled studies regarding the optimal management of childhood stroke in terms of the use of both antithrombotic drugs and anticoagulation are still needed in addition to longitudinal follow-up studies of children with stroke.