Background: Familial cerebral cavernous malformation (fCCM) is an autosomal dominant neurovascular disorder characterized by multiple lesions that increase risk of intracranial hemorrhage (ICH), seizures, and headaches. The impact of these symptoms on physical, mental, and social quality of life (QoL) in children with fCCM is unknown. We aimed to assess QoL domains and their associations with clinical symptoms and functional status at baseline and longitudinally in pediatric fCCM. Methods: Patient-Reported Outcomes Measurement Information System (PROMIS) surveys were completed by children or parent proxy for 66 pediatric fCCM participants (ages 5–17) enrolled in the Brain Vascular Malformation Consortium CCM study (2019–2025). Domain scores were converted to T-scores standardized to a U.S. pediatric reference population (mean=50, SD=10); higher scores reflect worse QoL. One-sample t-tests compared domain scores to population norms. Multivariable regression assessed associations between baseline PROMIS scores and prior ICH, seizures, headaches, or modified Rankin Scale (mRS) scores, adjusting for age, sex, and respondent type. Longitudinal analyses evaluated whether new symptom onset was associated with changes in PROMIS scores over time. Results: Among 66 participants (mean age 11.6±4.5), <50% reported prior ICH, seizures, or headaches; 93.3% had mRS scores of 0–1. PROMIS scores in anxiety (45.59 [95% CI: 42.51–48.67], p=0.006), depression (43.89 [41.63–46.14], p<0.001), fatigue (41.7 [39.03–44.37], p<0.001), and pain (43.29 [40.84–45.74], p<0.001) were significantly better than population norms. No significant baseline symptom-domain associations were observed, though moderate effect sizes were noted for prior ICH and worse fatigue (+3.83), mobility (+3.01), and sleep disturbance (+4.34); and for prior headache and fatigue (+3.64). Longitudinally, new headache onset was associated with increasing fatigue (+5.59 [0.046–11.13], p=0.048), with trends for worsening anxiety, pain, and sleep. Higher mRS scores correlated with worse pain (p=0.001), mobility (p=0.004), and sleep (p=0.011). Conclusions: PROMIS surveys captured QoL variation in pediatric fCCM, with moderate symptom-domain associations and significant correlations with mRS scores. Longitudinal changes in PROMIS scores tracked evolving symptom burden, particularly with new onset headaches and fatigue. Larger studies are needed to confirm PROMIS validity and refine its clinical utility in pediatric fCCM.

The superficial temporal artery–middle cerebral artery (STA–MCA) bypass remains a key extracranial–intracranial revascularization technique for moyamoya disease, complex aneurysms, and symptomatic steno-occlusive pathology not amenable to endovascular treatment. Effective bypass requires detailed knowledge of STA and MCA anatomy, comprehensive preoperative imaging, and meticulous microsurgical planning. We describe a stepwise operative strategy including donor and recipient vessel preparation, microanastomosis, and intraoperative patency assessment. Technical nuances, complication avoidance, and postoperative management are emphasized. This report outlines essential principles for safe and durable STA–MCA bypass revascularization.

Aromatic ʟ-amino acid decarboxylase (AADC) deficiency is a rare pediatric neurotransmitter disorder that typically necessitates lifelong care, and that carries a risk of childhood mortality. Eladocagene exuparvovec gene therapy is designed to restore AADC production. Study GT-002 (NCT04903288) is a phase 2, multicenter, open-label trial assessing the pharmacodynamics, safety, and efficacy of eladocagene exuparvovec administered to the putamen bilaterally in pediatric patients with AADC deficiency using a magnetic resonance (MR)-compatible cannula. Patients received eladocagene exuparvovec at 1.8 × 1011 vector genomes via the SmartFlow MR-compatible cannula in a single operative session. Endpoints include the change from baseline in cerebrospinal fluid homovanillic acid levels, motor milestone achievement, and safety. Here we report results from 48 weeks of follow-up. Mean (SD) cerebrospinal fluid homovanillic acid levels increased from baseline (22.5 [32.3] nmol/L; n = 13) to week 48 (55.3 [45.6] nmol/L; change from baseline: 28.3 [13.7] nmol/L; p = 0.0003; n = 9), indicating de novo dopamine production. At baseline (n = 13), all patients showed severe motor developmental delay; at week 48 (n = 12), nine achieved full head control, four could sit unassisted, two could stand with support, and two could walk independently to a toy. Overall, 260 treatment-emergent adverse events were reported in 13 patients; 259 were deemed unrelated and one likely unrelated to the MR-compatible cannula. No treatment-emergent adverse events led to study withdrawal and no deaths occurred. This study provides further evidence of the favorable pharmacodynamic, efficacy, and safety profile of eladocagene exuparvovec in children with AADC deficiency; intraputaminal administration using an MR-compatible cannula was well tolerated. Study GT-002 (NCT04903288) provides further evidence of the favourable pharmacodynamic, efficacy and safety profile of eladocagene exuparvovec gene therapy in children with AADC deficiency over 48 weeks and demonstrates that intraputaminal administration using an MR-compatible cannula was well tolerated, allowing for real-time MRI confirmation of cannula placement and infusate coverage, and for accurate dosing to the putamen.

Approximately 5-8% of intracranial aneurysms arise from the basilar artery apex (BAA). Given the basilar artery role in supplying the brainstem and the posterior cerebral circulation, the rates of morbidity and mortality are especially high in case of rupture. Although endovascular occlusion techniques are overall favored, thus leading to decreasing surgical expertise, complex BAA aneurysm may still require treatment with microsurgical occlusion. We describe our institutional perioperative protocol in the management of BAA aneurysms, focusing on surgical anatomy, approach selection, and intraoperative nuances.

Pediatric intracerebral hemorrhage (pICH) is a rare but serious neurologic emergency associated with significant morbidity. Although pICH accounts for nearly half of all pediatric strokes, it remains understudied, and dedicated evidence‐based management guidelines are lacking. To address this gap, the International Pediatric Stroke Organization convened a multidisciplinary international working group in 2020 to develop a comprehensive, consensus‐based framework for the acute evaluation and management of pICH in children aged 28 days to 18 years. The working group included child neurologists, neurointensivists, neurosurgeons, neuroradiologists, and neurointerventionalists. Subgroups conducted systematic literature reviews and formulated key clinical questions. A modified Delphi process was used to derive consensus statements across 6 domains: prehospital and emergency care, diagnostic imaging and workup, neurocritical care and medical management, neurosurgical and neurointerventional approaches, and identification of knowledge gaps. Through rounds of structured review and voting, 21 consensus statements were developed and approved. The process was endorsed by multiple professional societies. This represents the first international, multidisciplinary, multisociety consensus statement focused on the acute management of pICH in children. It provides structured, expert‐driven guidance to inform clinical decision‐making, reduce practice variability, and highlight areas for future research. These consensus statements aim to support clinicians worldwide in improving outcomes for children with pICH.

BACKGROUND:Familial cerebral cavernous malformation (fCCM) is characterized by multiple brain lesions affecting quality of life. PROMIS-29 (Patient-Reported Outcomes Measurement Information System 29) is a quality of life survey validated in some neurological diseases but not in fCCM. We assessed the reliability, validity, and association of PROMIS-29 in fCCM with clinical symptoms and with the modified Rankin Scale. METHODS:PROMIS-29 surveys assessing 7 quality of life domains were completed by 198 patients with fCCM ≥18 years old in the Brain Vascular Malformation Consortium cerebral cavernous malformation study. Raw domain scores were converted to T scores standardized to a reference population (mean 50±10) and tested using intercept-only regression (P≤0.05). Linear mixed models tested whether domain scores were associated with age, sex, clinical symptoms at time of first survey, or with modified Rankin Scale score. RESULTS:PROMIS domains had high reliability (Cronbach α >0.85). Patients with fCCM reported significantly worse anxiety (52.71 [95% CI, 51.23-54.20]), pain (52.50 [95% CI, 50.93-54.07]), and physical functioning (52.96 [95% CI, 51.40-54.52]), but better social participation (46.95 [95% CI, 45.35-48.54]) versus reference. Prior intracranial hemorrhage was associated with worse anxiety (+3.11 [95% CI, 0.10-6.12]), fatigue (+3.68 [95% CI, 0.61-6.76]), physical functioning (+3.79 [95% CI, 0.74-6.84]), and social participation (+4.42 [95% CI, 1.28-7.56]). Headaches were associated with worse depression (+3.17 [95% CI, 0.18-6.17]), fatigue (+4.14 [95% CI, 0.70-7.59]), pain (+3.88 [95% CI, 0.40-7.37]), and sleep disturbance (+2.94 [95% CI, 0.03-5.85]). Modified Rankin Scale score was weakly to moderately and positively associated with all domains except sleep disturbance (0.01≤R2≤0.55). CONCLUSIONS:PROMIS domains were reliable and correlated with modified Rankin Scale score and symptoms in fCCM, identifying affected domains beyond physical functioning. Future studies should determine whether changes in health domains are associated with fCCM disease severity and further evaluate clinical usefulness of PROMIS.

Paraclinoid aneurysms continue to present a surgical challenge, even in the modern endovascular era. Although these aneurysms are uncommon, surgical clipping remains the treatment of choice in select cases. Successful surgical management requires both extensive experience and a comprehensive understanding of paraclinoid anatomy. In this report, we outline our approach to planning and surgical techniques for managing paraclinoid aneurysms.

BACKGROUND AND OBJECTIVES:Despite many publications about cavernous malformations (CMs), controversy remains regarding diagnostic and management strategies. To update evidence-based guidelines for the clinical management of brain and spinal cord CMs. METHODS:The Alliance to Cure CMs, the patient support group in the United States advocating on behalf of patients and research in CM, convened a multidisciplinary writing group comprising expert CM clinicians to help summarize the existing literature related to the clinical care of CM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and imaging standards, (4) neurosurgical considerations, and (5) neurological considerations. Building on prior evidence-based recommendations reflecting literature review through October 2014, the group conducted a systematic review of the more recent literature, identified references for mandatory citation, rated evidence, developed recommendations, and established consensus according to a prespecified protocol. Finally, the writing group outlined remaining knowledge gaps and controversies to guide future research. RESULTS:From 2672 publications published between October 1, 2014, and March 15, 2023, and meeting key word criteria, 234 were selected based on prearticulated criteria for mandatory consideration in evidence-based recommendations. Topic authors used these and other supporting references to summarize current knowledge and arrive at 53 management recommendations, with unanimous consensus based on a Delphi process. These were rated by class (strength of recommendation) and level (quality of evidence) per the American Heart Association/American Stroke Association criteria. Eighteen recommendations were class 1 (34%), class 2 in 31 (58%), and class 3 in 4 (8%). Three were level A (6%), 19 (36%) were level B, and 31 (58%) were level C. CONCLUSION:Current evidence supports prior and new recommendations for the management of CMs, but many reflect moderate classes and low levels, mandating further research to better inform clinical practice.

Up to 40% of intracranial aneurysms arise from the anterior cerebral artery and anterior communicating artery (ACA-ACoA) complex. The vast variability of vessel anomalies and the surrounding critical structures correlate with severe morbidity and mortality rates in case of rupture. In the era of cutting-edge advantages of endovascular procedures, surgical expertise is reducing. This article describes our institutional surgical technique in managing ACoA aneurysms, focusing on anatomical variants, approach selection, and technical intraoperative nuances.

Background: Cerebrovascular accidents (CVA) are one of the most devastating neurologic manifestations of childhood-onset systemic lupus erythematosus (cSLE). The spectrum of CVA in cSLE (CVAcSLE) includes thromboembolic, ischemic, and hemorrhagic events. Despite the severity and potentially disabling effects of CVA, large epidemiologic studies are lacking. Studies of adult-onset systemic lupus erythematosus (aSLE) suggest higher CVA severity and poorer outcomes with aSLE compared to other adults with CVA. Comparative studies on CVA in aSLE and cSLE are lacking. Objectives: To understand the epidemiology of CVAcSLE, and compare CVA outcomes between cSLE and aSLE. Methods: This retrospective cohort study utilized de-identified data over a 20-year period from an international federated real-world patient database (TriNetX). We included all patients with ICD-9 and/or ICD-10 codes corresponding to SLE. The TriNetX database automatically excludes patients greater than 90 years old to maintain confidentiality of the patients. We defined cSLE and aSLE as patients aged ≤ 18 years and ≥ 19 years respectively at the first recorded ICD code corresponding to SLE. We defined CVA as the presence of ICD-9 and/or ICD-10 codes corresponding to transient ischemic attack and/or CVA. Results: Of the 112, 081, 954 patients in the TriNetX cohort, 21803 (0.02%) patients had SLE. Most patients with SLE were female (86%), White (66%) and non-Hispanic (89%) (Table 1). The prevalence of SLE was highest in the United States South compared to other regions (Table 1). The prevalence of CVA was 19% (n = 4123) in SLE patients overall, 8% (n = 30) in cSLE and 19% (n = 4093) in aSLE. In both cSLE and aSLE, the prevalence of CVA was highest in White patients followed by Black and other races; and also higher in non-Hispanic versus Hispanic patients. There was no significant difference in CVA prevalence by sex in both cSLE and aSLE. The odds of having CVA in aSLE was higher than in cSLE [OR 2.90; 95% CI (2.00, 4.21)]. The significantly higher risk in aSLE versus cSLE remained even after adjusting for age, sex, and race [OR 2.19; 95% CI (1.42 – 3.37)]. The risk of CVA was higher in females versus males [OR 1.16; 95% CI (1.05, 1.29)]. There was no significant difference in the 90-day readmission rate following CVA in cSLE compared to aSLE. Conclusion: cSLE is associated with a high risk of CVA as 1 out of 12 children with cSLE will develop a CVA. Given that aSLE patients with CVA have a higher risk of CVA recurrence, and poorer outcomes compared to other non-SLE adults with CVA, further studies are needed on CVA risk factors and longer-term outcomes in cSLE. REFERENCES: NIL. Acknowledgements: This research was funded in part by the 2023 Lupus Research Alliance Diversity in Lupus Research Career Development Award, by NIAMS P30 Core Center grant (AR076316), and the University of Cincinnati Center for Clinical and Translational Science and Training. Disclosure of Interests: None declared.

Hemorrhagic stroke (HS) is an important cause of neurologic morbidity and mortality in children and is more common than ischemic stroke between the ages of 1 and 14 years, a notable contradistinction relative to adult stroke epidemiology. Rapid neuroimaging is of the utmost importance in making the diagnosis of HS, identifying a likely etiology, and directing acute care. Computed tomography and MR imaging with flow-sensitive MR imaging and other noninvasive vascular imaging studies play a primary role in the initial diagnostic evaluation. Catheter-directed digital subtraction angiography is critical for definitive diagnosis and treatment planning.

OBJECTIVE:Cerebral revascularization surgery (CRS) has been used to prevent stroke in children with sickle cell disease (SCD) and cerebral vasculopathy (e.g., moyamoya syndrome). While results suggest that it may be an effective treatment, surgical indications have not been well defined. This study sought to determine indications for offering revascularization surgery in centers with established sickle cell programs in the US. METHODS:Three sequential surveys utilizing the Delphi methodology were administered to neurosurgeons participating in the Stroke in Sickle Cell Revascularization Surgery study. Respondents were presented with clinical scenarios of patients with SCD and varying degrees of ischemic presentation and vasculopathy, and the group's agreement to offer surgical revascularization was measured. Consensus was defined as ≥ 75% similar responses. RESULTS:The response rate to all 3 surveys was 100%. Seventeen neurosurgeons from 16 different centers participated. The presence of moyamoya collaterals (MMCs) and arterial stenosis matching an ischemic distribution yielded the strongest recommendations to offer surgery. There was consensus to offer revascularization in the presence of MMCs and at least 50% arterial stenosis matching an ischemic distribution. In contrast, there was no consensus to offer revascularization with 50%-70% stenosis not matching an ischemic presentation in the absence of MMCs. The presence of the ivy sign in the distribution of the stenotic artery also contributed to the consensus to offer surgery in certain scenarios. CONCLUSIONS:There were several clinical scenarios that attained consensus to offer surgery; the strongest was moderate to severe arterial stenosis that matched the distribution of ischemic presentation in the presence of MMCs. Radiological findings of decreased cerebral flow or perfusion also facilitated attaining consensus to offer surgery. The findings of this study reflect expert opinion about questions that deserve prospective clinical research. Determination of indications for CRS can guide clinical practice and aid the design of prospective studies.

Objective To investigate the prevalence and predictors of hereditary hemorrhagic telangiectasia (HHT) and capillary-malformation arteriovenous malformation (CM-AVM) syndrome among children with no prior personal or family history of these diseases who presented with an arteriovenous shunt lesion. Study design A retrospective chart review was completed on patients aged 0 through 21 years with arteriovenous shunt lesions evaluated at our Cerebrovascular Center. Diagnosis of definite or suspected HHT or CM-AVM was based on clinical features and genetic testing. Associations between final diagnosis and type and number of lesions, epistaxis, telangiectasias, CM, and pulmonary AVMs were assessed. Results Eighty-nine patients were included. Thirteen (14.6%) had definite HHT, 11 (12.4%) suspected HHT, and 4 (4.5%) definite CM-AVM. Having >= 2 episodes of epistaxis/year and >= 2 sites with telangiectasias were each associated with definite HHT (P<.001). Having >= 2 CM was associated with definite CM-AVM (P<.001). Pulmonary AVM was associated with increased odds of having definite HHT (OR = 6.3, 95% CI: 1.2-33.4). Multiple lesions (OR = 24.5, 95% CI: 4.5-134.8) and arteriovenous fistulas (OR = 6.2, 95% CI: 1.9-20.3) each increased the likelihood of having definite HHT or CM-AVM. Genetic testing was positive in 31% of patients tested. Conclusions We recommend that children with neurovascular shunt lesions be offered genetic testing and undergo further evaluation for HHT and CM-AVM. Awareness and early diagnosis of these conditions is a critical step toward improving long-term outcomes and preventing disease-associated complications.

Significance Shuntodynia is patient reported pain at the site of the implanted ventriculoperitoneal (VP) shunt. Pediatric hydrocephalus requiring shunt placement is a chronic and prevalent standard of care treatment and requires lifetime management. Shuntodynia is a subjective measure of shunt dysfunction. Quantitative, white-light tissue spectroscopy could be used to objectively identify this condition in the clinic. Aim Pediatric subjects were recruited for optical sensing during routine clinical follow-up visits, post-VP shunt implantations. Acquired optical signals were translated into skin-hemodynamic signatures and were compared between subjects that reported shuntodynia versus those that did not. Approach Diffuse reflectance spectroscopy (DRS) measurements were collected between 450 and 700 nm using a single-channel fiber-optical probe from (N=35) patients. Multiple reflectance spectra were obtained by the attending physician from regions both proximal and distal to the VP shunt sites and from a matched contralateral site for each subject. Acquired reflectance spectra were processed quantitatively into functional tissue optical endpoints. A two-way, repeated measures analysis of variance was used to assess whether and which of the optical variables were statistically separable, across subjects with shuntodynia versus those without. Results Analyses indicated that intrapatient differences in vascular oxygen saturation measured between shunt sites relative to that obtained at the scar or contralateral sites was significantly lower in the pain group. We also find that the total hemoglobin concentrations at the shunt site were lowest relative to the other sites for subjects reporting pain. These findings suggest that shuntodynia pain arises in the scalp tissue around the implanted shunts and may be caused due to hypoxia and inflammation. Conclusions Optically derived hemodynamic variables were statistically significantly different in subjects presenting with shuntodynia relative to those without. DRS could provide a viable mode in routine bedside monitoring of subjects with VP shunts for clinical management and assessment of shuntodynia.

Background: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). Methods: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. Results: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p =.040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio= 0.22, 95% CI = 0.08-0.58, p =.002). Conclusions: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.

Background Intra-arterial chemotherapy (IAC) for the treatment of intraocular retinoblastoma has gained recognition as a method to improve ocular salvage; however, there is a paucity of evidence supporting treatment factors prognosticating ocular survival. Methods All patients with retinoblastoma treated with IAC at a single institution between December 2008 and December 2019 were evaluated. Patient demographics, tumor classification, prior treatments, procedural data, other non-IAC therapies, adverse reactions, procedural complications, ocular outcomes, and overall survival were assessed via retrospective chart review. Factors suggestive of increased ocular survival were identified via univariate and multivariate analyses. The impact of accrued treatment experience was evaluated by grouping eyes by the respective year, IAC treatment was initiated. Results Forty-nine eyes of 43 patients were treated for retinoblastoma with IAC (256 total procedures). At least grade 3 neutropenia was observed following 19% of IAC procedures. The risk of neutropenia was not statistically different between single or multidrug IAC. Comparing those who received balloon-assisted intra-arterial chemotherapy (bIAC) in more than two-thirds of cycles to those who did not, the risk of arterial access site complications was not statistically different. Multivariate analysis revealed a significantly lower risk of enucleation associated with treatment era in years (hazard ratio [HR] = 0.52-1.00, p < .05) and laser therapies (HR = 0.02-0.60, p < .05). Conclusions Ocular survival rates in patients treated with IAC for retinoblastoma at our institution have increased over time. Accrued treatment experience and programmatic changes have likely contributed. Larger, prospective series may lead to a better understanding of factors that consistently contribute to better ocular salvage.

Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80