Yield of genetic evaluation in non-syndromic pediatric moyamoya patients.

PURPOSE: Few guidelines exist for genetic testing of patients with moyamoya arteriopathy. This study aims to characterize the yield of genetic testing of non-syndromic moyamoya patients given the current pre-test probability. METHODS: All pediatric moyamoya patients who received revascularization surgery at one institution between 2018 and 2022 were retrospectively reviewed. Patients with previously diagnosed moyamoya syndromes or therapeutic cranial radiation were excluded. RESULTS: Of 117 patients with moyamoya, 74 non-syndromic patients (44 females, 59%) were eligible. The median age at surgery was 8.1 years. Neurosurgeons referred 18 (24%) patients for neurogenetic evaluation. Eleven (61%) patients subsequently underwent genetic testing. Eight (73%) patients had available testing results. Five (62.5%) of these patients had developmental delay compared to 16 (22%) of the entire cohort. Six (75%) patients who underwent genetic testing were found to have at least one genetic variant. These results led to diagnosis of a new genetic disorder for 1 (12.5%) patient and screening recommendations for 2 (25%) patients. An RNF213 variant in one patient led to recommendations for family member screening and pulmonary hypertension screening. Another patient was diagnosed with CBL disorder and referred for cancer screening. The median age at surgery in patients with clinically actionable findings was 4.6 years compared to 9.2 years in those who were referred for genetic testing. All 3 patients who had an actionable finding had developmental delay. CONCLUSION: It may be beneficial to refer moyamoya patients under 5 for genetic screening given the high likelihood of discovering actionable mutations.

Benefits and limitations of a dual faculty neurosurgeon approach to resection of pediatric craniopharyngioma.

PURPOSE: The utility and safety of including two neurosurgeons for tumor resections is unknown. This study compares outcomes among pediatric patients with craniopharyngiomas operated on with a dual or single surgeon approach (DSA, SSA). METHODS: A single-center review identified all craniopharyngioma transsphenoidal or craniotomy resections from 2000 to 2020. Surgical years of experience (YOE) and rates of 5-year reoperations, complications, recurrence, and postoperative radiotherapy were analyzed. RESULTS: Twenty-six transsphenoidal and 68 craniotomies were identified among 62 patients. Eleven transsphenoidal (42.3%) utilized DSA and 15 utilized (57.7%) SSA. Eight craniotomies (11.8%) were DSA and 60 (88.2%) were SSA. The surgeon for SSA transsphenoidal procedures had a median of 10.7 YOE (IQR: 9.9-13.7) versus 6.6 (IQR: 2.7-16; p = 0.058) for the lead surgeon in DSAs. The co-surgeon in transsphenoidal DSAs had a median of 27 YOE (IQR: 11.8-35.7). The surgeon for SSA craniotomies had a median of 19.3 YOE (IQR: 12.1-26.4) versus 4.5 years (IQR: 1.3-15.3; p = 0.017) for the lead surgeon in DSA cases. The co-surgeon in DSA craniotomies had a median of 23.2 YOE (IQR: 12.6-31.4). Case complexity was similar across transsphenoidal groups. DSA transsphenoidal resections had fewer complications (18% DSA vs. 33% SSA), reoperations (45% vs. 53%), and radiation therapy (9.1% DSA vs. 33% SSA) than SSA. CONCLUSION: Lead surgeons in DSAs are frequently junior surgeons while SSAs typically employ senior surgeons. Outcomes did not significantly differ between DSA and SSA. Mentorship through DSAs does not negatively affect patient care.

Two Sides of a Coin: Case Report of Unilateral Synangiosis and Contralateral Stroke Highlighting Consequences of Disease Progression and Efficacy of Revascularization in Sickle Cell Disease-Associated Moyamoya Syndrome.

Moyamoya syndrome increases the risk of stroke in sickle cell disease, but revascularization surgery can modify this risk. Collaborative management between hematology and neurosurgery offers effective strategies to reduce stroke risk in these patients. We describe a challenging case where a patient with sickle cell disease undergoing standard of care management as prescribed by the Stroke Prevention Trial in Sickle Cell Anemia and revascularization with pial synangiosis subsequently developed rapidly progressive disease in other cerebral vessels and suffered ischemic hemispheric stroke. This case not only demonstrates the success of management in accordance with the American Heart Association (AHA) and American Stroke Association (ASA) guidelines but also demonstrates critical areas where we lack understanding of disease progression.

Single-institution Series of Hirayama Disease in North America.

STUDY DESIGN: A retrospective chart review. OBJECTIVE: The aims of this study were to review pathophysiology, workup, and treatment for Hirayama disease (HD); and to assess outcomes from a single institution. SUMMARY OF BACKGROUND DATA: HD is a rare, painless, cervical myelopathy with distal upper extremity weakness, muscle wasting, and spinal cord atrophy. Disease progression-a consequence of repeat flexion injury-occurs up to 5 years from the initial diagnosis. METHODS: Single-institution review of pediatric HD patients from 2010 to 2020. RESULTS: Patients (n=10 male, n=2 female) presented in the second decade (14-20 y) with painless progressive distal upper extremity weakness and atrophy without sensory loss. Electromyography (n=12) demonstrated denervation in C7-T1 myotomes and flexion/extension magnetic resonance imaging showed focal cord atrophy and anterior displacement of the posterior dura with epidural enhancement in flexion. Treatment included observation and external orthoses (n=9) and anterior cervical discectomy with fusion (n=3). One of the 9 patients managed conservatively experienced further deterioration; no patient who underwent anterior cervical discectomy with fusion progressed. CONCLUSIONS: Patients with HD require a multidisciplinary approach to diagnosis and treatment to preserve function. Treatment is preventive and aims to minimize flexion injury by inhibiting motion across involved joints. First-line management is avoidance of neck flexion and use of rigid orthosis; in cases of failed conservative management and/or rapid clinical deterioration, surgical fixation can be offered.

Management of Choroid Plexus Tumors and the Benefit of Preoperative Embolization in Pediatric Patients: Report of 46 Cases from a Single Institution.

OBJECTIVE: Optimal choroid plexus tumor (CPT) treatment involves gross total resection; however, intraoperative hemorrhage risk remains significant given tumor vascularity. This study describes pediatric CPT management and identifies patients most likely to benefit from preoperative embolization. METHODS: CPTs resected from 1997 to 2021 were included. The characteristics of embolized patients were compared to nonembolized patients; nonembolized patients were further stratified based on open vascular control-pedicle feeder ligation versus no pedicle ligation prior to tumor debulking. Statistical analyses identified factors associated with estimated blood loss (EBL), transfusion, length of stay, and complications. RESULTS: Among the 46 CPT cases identified, 98% achieved gross total resection, and 15% received embolization. Embolized patients were younger, smaller, and had larger tumors compared to nonembolized patients (median: 0.8 vs. 2.1 years; 9.3 vs. 14.4 kg; 91.08 vs. 5.5 cm3). Transfused patients were similarly younger and smaller (P < 0.05) than nontransfused patients. Among nonembolized patients, open vascular control was achieved in smaller tumors (<13 cm3) with significantly lower EBL (P = 0.002). Higher EBL was observed in patients with larger tumors, hydrocephalus, transependymal edema, vomiting, lethargy, and developmental regression (all P < 0.05). Patients with lethargy had longer hospital stays and a higher likelihood of postoperative complications (P < 0.05). There were no significant differences in complication rates between the embolization and nonembolization groups. CONCLUSIONS: Despite higher surgical risk profiles, embolized patients had similar complication rates and postoperative hydrocephalus management as nonembolized patients. Embolization was particularly beneficial in patients at high risk for surgical morbidity, such as those <2 years, weighing <10 kg, and with a tumor volume >15 cm3.

Optic Nerve Edema in Pediatric Middle Cranial Fossa Arachnoid Cysts: Report of 51 Patients From a Single Institution.

BACKGROUND: Middle fossa arachnoid cysts (MFACs) are rare, congenital lesions that may rupture and cause symptoms of elevated intracranial pressure. We sought to describe the presence of and factors associated with optic nerve edema in MFACs, focusing on the utility of ophthalmologic evaluations for guiding cyst management. METHODS: We reviewed clinical and radiographic information for all patients with MFACs with ophthalmologic evaluations at our institution. Headache, cranial nerve palsy, emesis, altered mental status, fatigue, and seizures were considered MFAC-related symptoms. Univariate and multivariable analyses evaluated factors associated with optic edema. RESULTS: Fifty-one patients between 2003 and 2022 were included. Cysts were a median volume of 169.9 cm3 (interquartile range: 70.5, 647.7). Evidence of rupture with subdural hematoma/hygroma occurred in 19 (37.3%) patients. Eighteen (35.3%) patients underwent surgery for their cyst and/or rupture-associated intracranial bleed. Eleven (21.6%) patients had optic edema; all were symptomatic and experienced cyst rupture. Ten of these patients received surgery. Postoperatively, optic edema resolved in 80% of cases. Cyst volume and symptoms were not associated with optic edema; however, patients with ruptured cysts, particularly those with traumatic rupture, were more likely to have optic edema and receive surgery (P < 0.001). CONCLUSIONS: We found optic edema in 21.6% of evaluated MFACs, and this comprised of 57.9% of ruptured cases. Optic edema was not found in unruptured cysts. Cyst fenestration improved optic edema and patient symptoms. In conjunction with clinical history and neuroimaging, optic edema may help guide MFAC management, particularly in patients with cyst rupture.

Safety of Concomitant Cortical and Thalamic Stereoencephalography Explorations in Patients With Drug-Resistant Epilepsies.

BACKGROUND AND OBJECTIVES: Intracranial electrophysiology of thalamic nuclei has demonstrated involvement of thalamic areas in the propagation of seizures in focal drug-resistant epilepsy. Recent studies have argued that thalamus stereoencephalography (sEEG) may aid in understanding the epileptogenic zone and treatment options. However, the study of thalamic sEEG-associated hemorrhage incidence has not been investigated in a cohort study design. In this article, we present the largest retrospective cohort study of sEEG patients and compare hemorrhage rates between those with and without thalamic sEEG monitoring. METHODS: Retrospective chart review of clinical and epilepsy history, electrode implantation, rationale, and outcomes was performed for 76 patients (age 20-69 years) with drug-resistant epilepsy who underwent sEEG monitoring at our institution (2019-2022). A subset of 38% of patients (n = 30) underwent thalamic monitoring of the anterior thalamic nucleus (n = 14), pulvinar nucleus (n = 25), or both (n = 10). Planned perisylvian orthogonal sEEG trajectories were extended to 2- to 3-cm intraparenchymally access thalamic area(s).The decision to incorporate thalamic monitoring was made by the multidisciplinary epilepsy team. Statistical comparison of hemorrhage rate, type, and severity between patients with and without thalamic sEEG monitoring was made. RESULTS: Our approach for thalamic monitoring was not associated with local intraparenchymal hemorrhage of thalamic areas or found along extended cortical trajectories, and symptomatic hemorrhage rates were greater for patients with thalamic coverage (10% vs 0%, P = .056), although this was not found to be significant. Importantly, patients with perisylvian electrode trajectories, with or without thalamic coverage, did not experience a higher incidence of hemorrhage (P = .34). CONCLUSION: sEEG of the thalamus is a safe and valuable tool that can be used to interrogate the efficacy of thalamic neuromodulation for drug-resistant epilepsy. While patients with thalamic sEEG did have higher incidence of hemorrhage at any monitoring site, this finding was apparently not related to the method of perisylvian implantation and did not involve any trajectories targeting the thalamus.

Magnetic Resonance Imaging/Angiography Versus Catheter Angiography for Annual Follow-up of Pediatric Moyamoya Patients: A Cost Outcomes Analysis.

BACKGROUND: Digital subtraction angiography (DSA) assesses revascularization in pediatric moyamoya patients after surgery, but MRI and angiography (MRI/A) may provide comparable data. OBJECTIVE: To evaluate DSA and MRI/A with respect to clinical utility in postoperative follow-up, complication profile, and relative cost at 1 year. METHODS: All pediatric moyamoya patients who received bilateral indirect revascularization between 2011 and 2020 were retrospectively reviewed at 1 institution. Patients who underwent MRI/A-only, DSA-only, or both after 1 year were compared. RESULTS: Eighty-two patients were included. At 1 year, patients who underwent either MRI/A (n = 29) or DSA (n = 40) had no significant differences in detection rate of new at-risk hypovascular territories (6.9% vs 2.5%, P = .568) or need for subsequent revascularization beyond the mean 40 ± 24-month follow-up period (3.4% vs 5.0%, P > .9). Among patients who underwent both MRI/A and DSA (n = 13), both studies identified the same at-risk territories. No patients experienced MRI/A-related complications, compared with 3 minor DSA-related complications. The use of MRI/A yielded a 6.5-fold reduction in cost per study vs DSA at 1 year. CONCLUSION: Using DSA to follow moyamoya patients after indirect revascularization is generally safe but associated with a low rate of minor complications and a 6.5-fold greater financial cost relative to MRI/A. These data support changing practice to eliminate the use of DSA when following routine bilateral moyamoya cases in the absence of clinical symptoms or specific concerns. Using MRI/A as the primary postoperative follow-up modality in this select population provides noninferior care and greater patient access, while reducing cost and potentially decreasing risk.

Positioning Transclival Tumor-Treating Fields for the Treatment of Diffuse Intrinsic Pontine Gliomas.

Diffuse intrinsic pontine glioma (DIPG) carries an extremely poor prognosis, with 2-year survival rates of <10% despite the maximal radiation therapy. DIPG cells have previously been shown to be sensitive to low-intensity electric fields in vitro. Accordingly, we sought to determine if the endoscopic endonasal (EE) implantation of an electrode array in the clivus would be feasible for the application of tumor-treating fields (TTF) in DIPG. Anatomic constraints are the main limitation in pediatric EE approaches. In our Boston Children's Hospital's DIPG cohort, we measured the average intercarotid distance (1.68 ± 0.36 cm), clival width (1.62 ± 0.19 cm), and clival length from the base of the sella (1.43 ± 0.69 cm). Using a linear regression model, we found that only clival length and sphenoid pneumatization were significantly associated with age (R2 = 0.568, p = 0.005 *; R2 = 0.605, p = 0.0002 *). Critically, neither of these parameters represent limitations to the implantation of a device within the dimensions of those currently available. Our findings confirm that the anatomy present within this age group is amenable to the placement of a 2 × 1 cm electrode array in 94% of patients examined. Our work serves to demonstrate the feasibility of implantable transclival devices for the provision of TTFs as a novel adjunctive therapy for DIPG.

External validation of the R2eD AVM scoring system to assess rupture risk in pediatric AVM patients.

OBJECTIVE: The assessment of hemorrhagic risk is of central importance in the management of pediatric brain arteriovenous malformations (AVMs). A recently published scoring system, the R2eD AVM (race, exclusive deep location or not, AVM size < 3 or ≥ 3, venous drainage exclusively deep or not, and monoarterial feeding or >1 arterial feeders) considers patient race and AVM location, size, venous drainage, and arterial supply and was successfully externally validated for use in adults to predict the risk of AVM hemorrhagic presentation. In this study the authors sought to externally validate the R2eD AVM score for prediction of hemorrhagic risk in the pediatric AVM population. METHODS: A pediatric database at Boston Children's Hospital was retrospectively reviewed for all patients with a diagnosis of intracranial AVM. Exclusion criteria included age > 21 years, multiple AVMs, and incomplete clinical/radiographic data. Demographic data and R2eD AVM score calculations were collected for all patients. Univariate binary logistic regression and multivariate stepwise backward elimination models were used to determine factors associated with hemorrhagic presentation. RESULTS: A total of 212 AVMs were identified in 212 patients with vascular anomalies from 1995 to 2021, and 144 patients met the inclusion criteria (74 [51.4%] male, 111 [77.1%] White), of whom 87 (60.4%) patients presented with rupture and 122 (84.7%) underwent resection. The mean age at surgery was 12 years (range 3 months to 20 years). The R2eD AVM scoring system was applied to each patient. The score components of size < 3 cm and exclusive deep venous drainage were significantly associated with rupture risk (p < 0.05). The complete model for the R2eD AVM score had an area under the curve of 0.671 (95% CI 0.586-0.757). CONCLUSIONS: This study demonstrated poor external validity of the R2eD AVM score in predicting pediatric AVM rupture risk. The results suggest that future studies are warranted to determine a better scoring method to capture pediatric rupture risk, given the significant differences in clinical presentation in pediatric compared with adult AVM patients.

Stereoelectroencephalography followed by combined electrode removal and MRI-guided laser interstitial thermal therapy or open resection: a single-center series in pediatric patients with medically refractory epilepsy.

OBJECTIVE: Stereoelectroencephalography (SEEG) and MRI-guided laser interstitial thermal therapy (MRgLITT) have emerged as safe, effective, and less invasive alternatives to subdural grid placement and open resection, respectively, for the localization and treatment of medically refractory epilepsy (MRE) in children. Reported pediatric experience combining these complementary techniques is limited, with traditional workflows separating electrode removal and ablation/resection. The authors describe the largest reported series of pediatric epilepsy patients who underwent MRgLITT following SEEG contrasted with a cohort that underwent craniotomy following SEEG, combining ablation/resection with electrode explantation as standard practice. METHODS: The medical records of all patients with MRE who had undergone SEEG followed by MRgLITT or open resection/disconnection at Boston Children's Hospital between November 2015 and December 2020 were retrospectively reviewed. Primary outcome variables included surgical complication rates, length of hospital stay following treatment, and Engel classification at the last follow-up. RESULTS: Of 74 SEEG patients, 27 (median age 12.1 years, 63% female) underwent MRgLITT and 47 (median age 12.1 years, 49% female) underwent craniotomy. Seventy patients (95%) underwent SEEG followed by combined electrode removal and treatment. Eight MRgLITT cases (30%) and no open cases targeted the insula (p < 0.001). Complication rates did not differ, although trends toward more subdural/epidural hematomas, infarcts, and permanent unanticipated neurological deficits were evident following craniotomy, whereas a trend toward more temporary unanticipated neurological deficits was seen following MRgLITT. The median duration of hospitalization after treatment was 3 and 5 days for MRgLITT and open cases, respectively (p = 0.078). Seizure outcomes were similar between the cohorts, with 74% of MRgLITT and craniotomy patients attaining Engel class I or II outcomes (p = 0.386) at the last follow-up (median 1.1 and 1.9 years, respectively). CONCLUSIONS: MRgLITT and open resection following SEEG can both effectively treat MRE in pediatric patients and generally can be performed in a two-surgery workflow during a single hospitalization. In appropriately selected patients, MRgLITT tended to be associated with shorter hospitalizations and fewer complications following treatment and may be best suited for focal deep-seated targets associated with relatively challenging open surgical approaches.

Optic nerve compression in craniopharyngioma by taut anterior cerebral arteries visualized in frontal and transsphenoidal exposures: illustrative cases.

BACKGROUND: During initial exposure and removal of craniopharyngioma in pediatric patients with severe visual field deficits, the authors have encountered severe deformation of the optic apparatus by taut anterior cerebral arteries as seen during both frontal craniotomy and transsphenoidal exposures. OBSERVATIONS: The authors report two pediatric patients with craniopharyngioma whose severe preoperative visual deficits were associated not only with large suprasellar masses but also with severe optic nerve and chiasm compression by taut anterior cerebral arteries. In each patient, the optic nerves were partially cleft by these vessels' indenting them. LESSONS: The role of a taut anterior cerebral artery complex in compression of the optic apparatus in patients with suprasellar tumors has been reported previously, but the intraoperative images in these two cases dramatically reveal this phenomenon.

Ivy sign: a diagnostic and prognostic biomarker for pediatric moyamoya.

OBJECTIVE: Ivy sign is a radiographic finding on FLAIR MRI sequences and is associated with slow cortical blood flow in moyamoya. Limited data exist on the utility of the ivy sign as a diagnostic and prognostic tool in pediatric patients, particularly outside of Asian populations. The authors aimed to investigate a modified grading scale with which to characterize the prevalence and extent of the ivy sign in children with moyamoya and evaluate its efficacy as a biomarker in predicting postoperative outcomes, including stroke risk. METHODS: Pre- and postoperative clinical and radiographic data of all pediatric patients (21 years of age or younger) who underwent surgery for moyamoya disease or moyamoya syndrome at two major tertiary referral centers in the US and Israel, between July 2009 and August 2019, were retrospectively reviewed. Ivy sign scores were correlated to Suzuki stage, Matsushima grade, and postoperative stroke rate to quantify the diagnostic and prognostic utility of ivy sign. RESULTS: A total of 171 hemispheres in 107 patients were included. The median age at the time of surgery was 9 years (range 3 months-21 years). The ivy sign was most frequently encountered in association with Suzuki stage III or IV disease in all vascular territories, including the anterior cerebral artery (53.7%), middle cerebral artery (56.3%), and posterior cerebral artery (47.5%) territories. Following surgical revascularization, 85% of hemispheres with Matsushima grade A demonstrated a concomitant, statistically significant reduction in ivy sign scores (OR 5.3, 95% CI 1.4-20.0; p = 0.013). Postoperatively, revascularized hemispheres that exhibited ivy sign score decreases had significantly lower rates of postoperative stroke (3.4%) compared with hemispheres that demonstrated no reversal of the ivy sign (16.1%) (OR 5.5, 95% CI 1.5-21.0; p = 0.008). CONCLUSIONS: This is the largest study to date that focuses on the role of the ivy sign in pediatric moyamoya. These data demonstrate that the ivy sign was present in approximately half the pediatric patients with moyamoya with Suzuki stage III or IV disease, when blood flow was most unstable. The authors found that reversal of the ivy sign provided both radiographic and clinical utility as a prognostic biomarker postoperatively, given the statistically significant association with both better Matsushima grades and a fivefold reduction in postoperative stroke rates. These findings can help inform clinical decision-making, and they have particular value in the pediatric population, as the ability to minimize additional radiographic evaluations and tailor radiographic surveillance is requisite.