Mechanical Thrombectomy for Pediatric Arterial Ischemic Stroke from Acute M2 Occlusion.

Pediatric large-vessel occlusion has a poor natural history. Recent retrospective studies have demonstrated the potential benefits, feasibility, and safety profile of mechanical thrombectomy in children. However, the role of thrombectomy in pediatric M2 occlusions remains uncertain. In this clinical report, we present a multicenter series of 6 pediatric patients with acute M2 occlusion (female = 1, male = 5; age range, 0.9-16.0 years, mean = 9.2). All 6 patients having undergone thrombectomy had excellent clinical outcomes (pediatric mRS = 0-1) at 3 months and final available follow-up (median, 12 months; range, 3-72 months). Factors relevant to treatment decision-making in pediatric M2 occlusions are discussed, including the important role of multidisciplinary team discussions during acute management.

Association Between Thrombectomy and Functional Outcomes in Pediatric Patients With Acute Ischemic Stroke From Large Vessel Occlusion.

Importance: Pediatric large vessel occlusion (LVO) stroke has a poor natural history. However, uptake of mechanical thrombectomy is hindered by a lack of clinical trial data in children. A randomized clinical trial is not feasible due to small sample sizes and absence of equipoise. Objective: To evaluate whether pediatric patients with acute LVO stroke who undergo thrombectomy have better clinical outcomes than matched patients managed conservatively. Design, Setting, and Participants: This matched case-control study used pooled stroke registry data from 5 tertiary referral hospitals in Australia and Canada from January 2011 to April 2022. Patients were aged 1 month to younger than 18 years with acute LVO stroke. Pooled data identified 31 thrombectomy patients and 46 control patients. Five patients undergoing thrombectomy with basilar artery occlusion were excluded due to insufficient controls. Using a hierarchal matching system (site of occlusion, age group, side of occlusion, and sex), deidentified consensus matching of patients and controls was undertaken while blinded to clinical outcome. Data were analyzed from July to November 2022. Exposure: In the case cohort, mechanical thrombectomy was undertaken for management of acute LVO stroke. The control cohort received medical treatment only. Main Outcomes and Measures: The primary outcome was the functional clinical status 3 months following stroke, measured by the pediatric modified Rankin Scale (mRS). Clinical outcomes were compared between groups using ordinal regression analysis. Results: Of 52 included patients, 31 (60%) were male, and the mean (SD) age was 10.3 (4.4) years. Matching was achieved for 26 children undergoing thrombectomy with 26 controls. There was no significant difference between groups for site or side of occlusion, age, sex, etiology, thrombolysis status, baseline Alberta Stroke Programme Early CT Score, or time since last seen well to presentation. Patients undergoing thrombectomy had superior clinical outcomes than control patients at 3 months on the pediatric mRS (odds ratio, 3.76; 95% CI, 1.32-10.67; P = .01). These superior outcomes were maintained at final follow-up (odds ratio, 3.65; 95% CI, 1.25-10.68; P = .02). Conclusions and Relevance: In the absence of a randomized clinical trial, this case-control study demonstrates better clinical outcomes with thrombectomy than medical management alone for pediatric patients aged 2 to 18 years with anterior circulation LVO stroke.

Incidence and Natural History of Pediatric Large Vessel Occlusion Stroke: A Population Study.

Importance: The incidence and natural history of large vessel occlusion (LVO) stroke in children is largely unknown. These knowledge gaps limit the uptake of reperfusion therapies and reduce the efficiency of pediatric acute stroke pathways. Objective: To determine the incidence and natural history of pediatric LVO stroke. Design, Setting, and Participants: This retrospective population-based cohort study was conducted between January 2010 and December 2019, with a mean (SD) follow-up of 37.0 (28.8) months. Admissions from all pediatric hospitals in the state of New South Wales, Australia, with a final diagnosis of arterial ischemic stroke (AIS) in patients 1 month to younger than 17 years were included. A total of 85 of 251 identified cases were excluded based on selection criteria. Data were analyzed from July 2020 to June 2021. Exposures: One-third of patients with LVO received mechanical thrombectomy with or without intravenous thrombolysis while the remainder were treated conservatively. Main Outcomes and Measures: The primary outcome was the pediatric modified Rankin Scale (ped-mRS) score 3 months after stroke. Ordinal logistic regression was used to compare non-LVO, LVO without thrombectomy, and LVO with thrombectomy groups. Results: Of 161 included patients, 56 (34.8%) were female, and the mean (SD) age was 6.1 (5.4) years. A total of 166 AIS admissions were studied, and clinical follow-up was available for 164 of 166 admissions. LVO was present in 39 admissions (23.5%). The incidence of LVO stroke was 0.24 per 100 000 patients per year (95% CI, 0.13-0.35). Patients with LVO who did not receive thrombectomy (n = 26) had poor neurological outcomes, with 19 (73.1%) experiencing moderate to severe disability or death (ped-mRS score of 3 to 6) at 3 months (6 of 12 patients receiving thrombectomy [50.0%]; 25 of 38 patients with LVO [65.8%]). Patients with LVO without thrombectomy had significantly worse clinical outcomes than patients with non-LVO at 3 months (odds ratio, 3.64; 95% CI, 1.68-7.87; P = .001). Most patients with LVO presented within time windows suitable for thrombectomy (27 of 39 [69.2%] within 6 hours; 35 of 39 [89.7%] within 24 hours). Conclusions and Relevance: In this population-based cohort study, the natural history of pediatric patients with LVO stroke treated conservatively was poor, with most experiencing lifelong disability or death. Nearly 90% of pediatric patients with LVO presented within time windows suitable for thrombectomy.

Current Concepts in Intracranial Interstitial Fluid Transport and the Glymphatic System: Part I-Anatomy and Physiology.

Normal physiologic function of organs requires a circulation of interstitial fluid to deliver nutrients and clear cellular waste products. Lymphatic vessels serve as collectors of this fluid in most organs; however, these vessels are absent in the central nervous system. How the central nervous system maintains tight control of extracellular conditions has been a fundamental question in neuroscience until recent discovery of the glial-lymphatic, or glymphatic, system was made this past decade. Networks of paravascular channels surrounding pial and parenchymal arteries and veins were found that extend into the walls of capillaries to allow fluid transport and exchange between the interstitial and cerebrospinal fluid spaces. The currently understood anatomy and physiology of the glymphatic system is reviewed, with the paravascular space presented as an intrinsic component of healthy pial and parenchymal cerebral blood vessels. Glymphatic system behavior in animal models of health and disease, and its enhanced function during sleep, are discussed. The evolving understanding of glymphatic system characteristics is then used to provide a current interpretation of its physiology that can be helpful for radiologists when interpreting neuroimaging investigations.

Current Concepts in Intracranial Interstitial Fluid Transport and the Glymphatic System: Part II-Imaging Techniques and Clinical Applications.

The glymphatic system is a recently discovered network unique to the central nervous system that allows for dynamic exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF). As detailed in part I, ISF and CSF transport along paravascular channels of the penetrating arteries and possibly veins allow essential clearance of neurotoxic solutes from the interstitium to the CSF efflux pathways. Imaging tests to investigate this neurophysiologic function, although challenging, are being developed and are reviewed herein. These include direct visualization of CSF transport using postcontrast imaging techniques following intravenous or intrathecal administration of contrast material and indirect glymphatic assessment with detection of enlarged perivascular spaces. Application of MRI techniques, including intravoxel incoherent motion, diffusion tensor imaging, and chemical exchange saturation transfer, is also discussed, as are methods for imaging dural lymphatic channels involved with CSF efflux. Subsequently, glymphatic function is considered in the context of proteinopathies associated with neurodegenerative diseases and traumatic brain injury, cytotoxic edema following acute ischemic stroke, and chronic hydrocephalus after subarachnoid hemorrhage. These examples highlight the substantial role of the glymphatic system in neurophysiology and the development of certain neuropathologic abnormalities, stressing the importance of its consideration when interpreting neuroimaging investigations. © RSNA, 2021.

Cavernous sinus embolisation prior to removal of penetrating foreign body in a 6-year-old child.

Transorbital penetrating foreign bodies are extremely rare in children and may penetrate the cavernous sinus or the underlying internal carotid artery. Parent vessel sacrifice and temporary balloon occlusion are feasible options for managing arterial injury during removal of the foreign body. Even in the absence of arterial injury, the ophthalmologist may encounter significant bleeding from the cavernous sinus deep in their operative field that is difficult to control. We present a case of a 6-year-old child with a stick penetrating the left superior orbit to enter the cavernous sinus but sparing the internal carotid artery. We describe the first reported experience of prophylactic coil embolisation of the cavernous sinus to minimise intraoperative bleeding during transorbital removal of a foreign body with an excellent clinical outcome.

Subcaudate Tractotomy White Matter Anatomy and Variability: A Diffusion Tensor Imaging Study.

BACKGROUND: Subcaudate tractotomy is a functional ablative procedure performed for treatment-resistant psychiatric disease, targeting the white matter tracts ventral to the head of the caudate nucleus. The white matter anatomy of this region has extensive interindividual variability, and this is thought to impact upon the treatment response to ablative and deep brain stimulation procedures. OBJECTIVE: We aim to assess in detail the white matter tract anatomy and topographic variability underlying subcaudate tractotomy. METHODS: 74 non-depressed adult volunteers underwent MRI including diffusion tensor imaging. Individualized regions of interest were formed in both hemispheres using native non-normalized data to simulate a subcaudate tractotomy. Tractography and analysis were performed and the exact tract locations measured including mean distances and standard deviations to assess variability. RESULTS: The cingulum bundle, uncinate fasciculus, corticostriatal fibres, and corticothalamic fibres were consistently demonstrated. The location of the cingulum bundle was consistent across subjects, but there was extensive interindividual variability in the topographic location of the other tracts. CONCLUSION: We have demonstrated a detailed analysis of the white matter tracts and their anatomical variability underlying subcaudate tractotomy. This has significant implications for neurosurgical targeting.

Reduced integrity of the uncinate fasciculus and cingulum in depression: A stem-by-stem analysis.

INTRODUCTION: The subgenual cingulate gyrus (Brodmann's Area 25: BA25) is hypermetabolic in depression and has been targeted successfully with deep brain stimulation. Two of the white matter tracts that play a role in treatment response are the uncinate fasciculus (UF) and the cingulum bundle. The UF has three prefrontal stems, the most medial of which extends from BA25 (which deals with mood regulation) and the most lateral of which extends from the dorso-lateral prefrontal cortex (concerned with executive function). The cingulum bundle has numerous fibers connecting the lobes of the cerebrum, with the longest fibers extending from BA25 to the amygdala. We hypothesize that there is reduced integrity in the UF, specific to the medial prefrontal stems, as well as in the subgenual and amygdaloid fibers of the cingulum bundle. Our secondary hypothesis is that these changes are present from the early stages of depression. OBJECTIVE: Compare the white matter integrity of stems of the UF and components of the cingulum bundle in first-onset depressed, recurrent/chronic depressed, and non-depressed control subjects. METHODS: Depressed patients (n = 103, first-onset = 57, chronic = 46) and non-depressed control subjects (n = 74) underwent MRI with 32-directional DTI sequences. The uncinate fasciculi and cingulum bundles were seeded, and the fractional anisotropy (FA) measured in each of the three prefrontal stems and the body of the UF, as well as the subgenual, body, and amygdaloid fiber components of the cingulum bundle. FA measurements were compared between groups using ANOVA testing with post-hoc Tukey analysis. RESULTS: There were significant reductions in FA in the subgenual and polar stems of the UF bilaterally, as well as the subgenual and amygdaloid fibers of the cingulum bundle, in depressed patients compared with controls (p < 0.001). There was no significant difference seen in the lateral UF stem or the main body of the cingulum. No significant difference was demonstrated in any of the tracts between first-onset and chronic depression patients. CONCLUSION: Depressed patients have reduced white matter integrity in the subgenual and polar stems of the uncinate fasciculi but not the lateral stems, as well as in the subgenual and amygdaloid cingulum fibers. These changes are present from the first-onset of the disease.

Diffusion tensor imaging to aid subgenual cingulum target selection for deep brain stimulation in depression.

BACKGROUND: The most investigated target for deep brain stimulation in depression is the subgenual cingulate gyrus (Cg25) which has been shown to be a critical hub for signalling in the condition. Diffusion tensor imaging (DTI) is a form of MR sequence that can visualise white matter connections and potentially aid target selection. OBJECTIVES: To assess whether targets selected using DTI to find the area of maximal tract crossover (maximal isotropy) underlying the subgenual cingulum differ significantly in location from those selected using standard T(2) sequences. METHODS: Fifty-nine non-depressed adult volunteers underwent MR imaging using T(1), T(2) and DTI sequences of the brain. Each patient had targets selected for both hemispheres using both T(2) and DTI sequences. The significance of the differences in coordinates in all three dimensions was tested using the paired t test. RESULTS: There was a significant difference in the mediolateral (x) and dorsoventral (z) coordinates of DTI targets when compared with T(2) targets (p < 0.001). CONCLUSIONS: Targets within Cg25 selected using DTI are significantly different in location from those selected using T(2) sequences and have the potential to enhance treatment outcome by reducing the impact of interindividual variability.

Successful treatment of six cases of indirect carotid-cavernous fistula with ethylene vinyl alcohol copolymer (Onyx) transvenous embolization.

BACKGROUND: Endovascular transvenous treatments have become the mainstay in the management of indirect carotid-cavernous fistulas (CCFs). However, the standard coil techniques are associated with a substantial failure and complication rate. The ethylene vinyl alcohol copolymer (Onyx) Liquid Embolization System has advantages over coils, including the ability to penetrate and occlude vessels of small caliber or with difficult access. METHODS: This was a review of 5 consecutive patients with indirect type D CCFs who underwent 6 procedures using the Onyx system alone at the Prince of Wales Hospital, Sydney, between December 2005 and May 2007. The cavernous sinus was catheterized with MTI Echelon-10 or Rebar-14 microcatheters via the femoral vein using an inferior petrosal approach to the cavernous sinus in 5 procedures and directly via the superior ophthalmic vein in 1 procedure. RESULTS: All 5 patients had complete closure of the fistulas as seen on imaging and full reversal of ophthalmic manifestations without lingering complications and with substantially shorter procedure times than with conventional approaches. CONCLUSIONS: The Onyx system is a safe and useful method of closing indirect CCFs transvenously. This is the first series report of the use of the Onyx system alone in the treatment of these vascular abnormalities.

How rapidly does cerebral swelling follow trauma? Observations using an animal model and possible implications in infancy.

To study the speed of development of cerebral edema in an animal model, five 2-year-old male anesthetized Merino sheep were impacted in the left temporal region by a humane stunner. Following the induction of blunt craniocerebral trauma a highly significant increase in intracranial pressure (ICP) values occurred relative to control animals (ANOVA, p<0.001). An immediate increase in ICP to values over 20 mmHg occurred within the first 30 min, and by 60 min, mean ICP was over 25 mmHg (p<0.05 versus controls). ICP continued to increase with time such that by 4h after injury, values were consistently greater than 30 mmHg (p<0.001 versus controls). The mean brain tissue oxygenation (P(bt)O(2)) in control animals over the 4h monitoring period was 52+/-8 mmHg with a highly significant (ANOVA, p<0.001) and early decrease in P(bt)O(2) recorded in impacted animals following craniocerebral trauma. By 30 min after injury, P(bt)O(2) was approximately 35 mmHg, while by 60 min, it had decreased to 20+/-2 mmHg (p<0.001 versus controls). The P(bt)O(2) continued to decline with time such that by 4h, the value was 14+/-2 mmHg (p<0.01 versus controls), or 27% of the mean control values. These data demonstrate that vasoreactive changes with increased blood volume and interstitial transfer of fluid may occur rapidly within brain tissue after blunt trauma. Detection of cerebral swelling at autopsy may not, therefore, imply prolonged survival.