Relative anemia and perioperative stroke in children with moyamoya.

OBJECTIVES: Surgical revascularization for moyamoya arteriopathy decreases long-term stroke risk but carries a risk of perioperative ischemic complications. We aimed to evaluate modifiable stroke risk factors in children undergoing surgical revascularization for moyamoya. MATERIALS AND METHODS: In this exploratory, single-center, retrospective cohort study, medical records of pediatric patients undergoing surgical revascularization for moyamoya arteriopathy at our center between 2003 and 2021 were reviewed. Candidate modifiable risk factors were analyzed for association with perioperative stroke, defined as ischemic stroke ≤7 days after surgery. RESULTS: We analyzed 53 surgeries, consisting of 39 individual patients undergoing indirect surgical revascularization of 74 hemispheres. Perioperative ischemic stroke occurred following five surgeries (9.4%). There were no instances of hemorrhagic stroke. Larger pre-to-postoperative decreases in hemoglobin (OR 3.90, p=0.017), hematocrit (OR 1.69, p=0.012) and blood urea nitrogen (OR 1.83, p=0.010) were associated with increased risk of perioperative ischemic stroke. Weight-adjusted intraoperative blood loss was not associated with risk of perioperative ischemic stroke (OR 0.94, p=0.796). Among children with sickle cell disease, all of whom underwent exchange transfusion within one week prior to surgery, none experienced perioperative stroke. CONCLUSIONS: Decreases in hemoglobin, hematocrit, and blood urea nitrogen between the preoperative and postoperative periods are associated with increased risk of perioperative stroke. These novel findings suggest that dilutional anemia, possibly due to standardly administered hyperhydration, may increase the risk of perioperative stroke in some children with moyamoya. Further work optimizing both mean arterial pressure and oxygen-carrying capacity in these patients, including consideration of alternative blood transfusion thresholds, is necessary.

Transcranial Doppler in Childhood Moyamoya: An Underutilized Tool?

BACKGROUND: Children with moyamoya are at high risk for incident and recurrent stroke. Transcranial Doppler (TCD) ultrasound is an attractive option to screen high-risk populations for moyamoya and to provide stroke risk stratification information due to its safety and cost-effectiveness. We used TCD to evaluate cerebral blood flow velocities in children with presurgical moyamoya and to determine if velocities differ between children with stable and unstable disease. METHODS: Fourteen participants aged ≤21 years with a radiographic diagnosis of moyamoya or moyamoya-like arteriopathy underwent a research TCD at a median age of 7.2 years. TCDs were performed outside of the setting of acute stroke and before surgical revascularization. Arteriopathy was classified as unstable if the participant had a stroke or transient ischemic attack within three months preceding the TCD. RESULTS: Middle cerebral artery and internal carotid artery (ICA) blood flow velocities were elevated. The median M1 velocity was 138 cm/s (interquartile range [IQR] 106 to 168). Individual M1 flow velocities were a median of 5.0 S.D.s above age-based normative values. The median distal ICA velocity was 146 cm/s (IQR 124 to 163). Individual ICA flow velocities were a median of 5.9 S.D.s above normative values. Participants with unstable arteriopathy had higher M1 velocities compared with those with stable arteriopathy (170 vs 119 cm/s, P = 0.0003). We did not identify velocity differences based on comorbid conditions or age. CONCLUSIONS: These preliminary data suggest that TCD is a promising tool for screening for cerebral arteriopathies in high-risk pediatric populations and assessment for unstable disease.

Seizures in Pediatric Moyamoya: Risk Factors and Functional Outcomes.

BACKGROUND: Children with moyamoya arteriopathy are at high risk for stroke and seizures. Risk factors for seizures and the impact of seizures on neurological outcomes in children with moyamoya are unknown. METHODS: This is a single-center retrospective cohort study of children with moyamoya evaluated between 2003 and 2021. Functional outcome was assessed using the Pediatric Stroke Outcome Measure (PSOM). Associations between clinical variables and seizure occurrence were assessed using univariate and multivariable logistic regression. Associations between clinical variables and final PSOM score were assessed using ordinal logistic regression. RESULTS: Eighty-four patients met inclusion criteria, and 34 (40%) children experienced seizure. Factors associated with seizures included moyamoya disease (vs syndrome; odds ratio [OR] 3.43, P = 0.008) and the presence of infarcts on baseline neuroimaging (OR 5.80, P = 0.002). Factors associated with decreased likelihood of experiencing seizures included older age at initial presentation (OR 0.82, P = 0.002) and asymptomatic (radiographic) presentation (OR 0.05, P = 0.006). Both older age at presentation (adjusted OR [AOR] 0.80, P = 0.004) and incidental radiographic presentation (AOR 0.06, P = 0.022) remained significant after adjusting for potential confounders. Seizures were associated with worse functional outcomes as assessed by the PSOM (regression coefficient 2.03, P < 0.001). This association remained significant after adjusting for potential confounders (adjusted regression coefficient 1.54, P = 0.025). CONCLUSIONS: Younger age and symptomatic presentation are associated with increased likelihood of seizures among children with moyamoya. Seizures are associated with worse functional outcomes. Prospective studies should clarify how seizures impact outcomes and how effective seizure treatment modifies this relationship.

Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics.

The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed "long COVID" or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, "brain fog", headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood-brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.