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Intellectual function and memory in children with moyamoya disease: relationship between Wechsler Intelligence Scale and Benton Visual Retention Test scores and regional cerebral blood flow

Satoshi Karashima, Akira Nakamizo, Koichi Arimura, and Koji Yoshimoto

OBJECTIVE

Intellectual function declines in about 30% of children with moyamoya disease (MMD). Memory function underpins higher order brain function, but the relationship between intellectual function and memory in pediatric MMD patients has not been well studied. This study aimed to investigate correlations between scores on the Wechsler Intelligence Scale for Children (WISC) and the Benton Visual Retention Test (BVRT), a visual memory test that can be administered to children, in children with MMD. Relationships between intellectual function or memory and regional cerebral blood flow (rCBF) have also not been well clarified in pediatric MMD patients. The authors also investigated associations between WISC or BVRT scores and rCBF in various brain regions.

METHODS

WISC and BVRT scores and rCBF were assessed in 17 children with ischemic-onset MMD before revascularization. Single-photon emission CT with 123I-iodoamphetamine was used to measure rCBF. Relationships between WISC and BVRT scores were evaluated using Spearman’s correlation coefficient and multivariate linear regression analysis. Cutoff values were identified for BVRT scores. Sensitivity and specificity were calculated to predict full-scale intelligence quotient (FSIQ) > 85 or ≤ 85. Associations between rCBF and WISC or BVRT scores were evaluated using linear regression analysis.

RESULTS

BVRT scores were significantly correlated with FSIQ and scores on the Working Memory Index (WMI), Processing Speed Index, and Verbal Comprehension Index (VCI)/Verbal Intelligence Quotient (VIQ) of WISC. Multivariate linear regression revealed that number correct score and number of errors score of BVRT were associated with FSIQ. As cutoff values, a number correct score of 5 and a number of errors score of 8 offered the most reliable predictors of FSIQ > 85 and ≤ 85, respectively. FSIQ correlated positively with rCBF in the right and left hemispheres, right and left ganglia, right and left thalamus, right and left cerebellum, right middle cerebral artery (MCA) territory, pons, and vermis. WMI score was positively associated with rCBF in the right hemisphere, right anterior cerebral artery territory, right MCA territory, right basal ganglia, right and left thalamus, right and left cerebellum, pons, and vermis.

CONCLUSIONS

BVRT score correlated well with WISC index scores, suggesting that BVRT may be helpful in screening for intellectual impairments in children with MMD. In the MCA territory, basal ganglia, thalamus, cerebellum, pons, and vermis, rCBF associated well with WISC index scores, suggesting that reduced rCBF in relevant brain regions may influence intellectual function.

Open access

Rapid brain MRI for image-guided ventricular catheter placement in pediatric patients: protocol and preliminary clinical outcomes

Grace Y. Lai, Andria Powers, Taylor Chung, and Peter P. Sun

OBJECTIVE

Neuronavigation is a useful adjunct for catheter placement during neurosurgical procedures for hydrocephalus or ventricular access. MRI protocols for navigation are lengthy and require sedation for young children. CT involves ionizing radiation. In this study, the authors introduce the clinical application of a 1-minute rapid MRI sequence that does not require sedation in young children and report their preliminary clinical experience using this technique in their pediatric population.

METHODS

All patients who underwent ventricular catheter placement at a children’s hospital using a rapid noncontrast MRI protocol, standard MRI, or head CT from July 2021 to August 2023 were included. Type of procedure, etiology of hydrocephalus, ventricle configuration and size, morphology of ventricles, need for adjunctive intraoperative ultrasound, duration of procedure, accuracy of catheter placement, and need for proximal revision within 90 days were retrospectively recorded and compared across imaging modalities.

RESULTS

Sixty-eight patients underwent 83 procedures: 21 underwent CT navigation, 29 standard MRI, and 33 rapid MRI. Patients who received standard MRI more often had tumor etiology, while those who underwent CT and rapid MRI had posthemorrhagic etiology (χ2 = 13.04, p = 0.042). Intraoperative ultrasound was required for 1 patient in the standard MRI group and 1 patient in the CT group. There was no difference in procedure time across groups (p = 0.831). On multivariable analysis, procedure time differed by procedure type, where external ventricular drain placement and proximal revision were faster (p < 0.001 and p < 0.028, respectively). Proximal revision due to obstruction within 90 days occurred in 3 cases (in the same patient with complex loculated hydrocephalus) in the rapid MRI group and 2 cases in the CT group.

CONCLUSIONS

Although this study was not powered for statistical inference, the authors report on the clinical use of a 1-minute rapid MRI sequence for neuronavigation in hydrocephalus or ventricular access surgery. There were no instances in which intraoperative ultrasound was required as an adjunct for procedures navigated with rapid MRI, and intraoperative time did not differ from that of standard navigation protocols.

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Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients

Gracie Garcia, Georgios Mantziaris, Stylianos Pikis, Chloe Dumot, L. Dade Lunsford, Ajay Niranjan, Zhishuo Wei, Priyanka Srinivasan, Lilly W. Tang, Roman Liscak, Jaromir May, Cheng-Chia Lee, Huai-Che Yang, Selcuk Peker, Yavuz Samanci, Ahmed M. Nabeel, Wael A. Reda, Sameh R. Tawadros, Khaled Abdel Karim, Amr M. N. El-Shehaby, Reem Emad Eldin, Ahmed Hesham Elazzazi, Nuria Martínez Moreno, Roberto Martínez Álvarez, Varun Padmanaban, Francis J. Jareczek, James McInerney, Kevin M. Cockroft, Juan Diego Alzate, Douglas Kondziolka, Manjul Tripathi, and Jason P. Sheehan

OBJECTIVE

The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients.

METHODS

Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation.

RESULTS

The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%–7.8%) at 1 year to 44% (95% CI 32%–55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%–62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%–16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed.

CONCLUSIONS

The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

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Complications following resection of primary and recurrent pediatric posterior fossa ependymoma

Armaan K. Malhotra, Liana Nobre, George M. Ibrahim, Abhaya V. Kulkarni, James M. Drake, James T. Rutka, Michael D. Taylor, Vijay Ramaswamy, Peter B. Dirks, and Michael C. Dewan

OBJECTIVE

Extent of resection (EOR) is the most important modifiable prognostic variable for pediatric patients with posterior fossa ependymoma. An understanding of primary and recurrent ependymoma complications is essential to inform clinical decision-making for providers, patients, and families. In this study, the authors characterize postsurgical complications following resection of primary and recurrent pediatric posterior fossa ependymoma in a molecularly defined cohort.

METHODS

The authors conducted a 20-year retrospective single-center review of pediatric patients undergoing resection of posterior fossa ependymoma at the Hospital for Sick Children in Toronto, Canada. Complications were dichotomized into major and minor groups; EOR was compared across complication categories. The association between complication occurrence with length of stay (LOS) and mortality was also assessed using multivariable regressions.

RESULTS

There were 60 patients with primary resection included, 41 (68%) of whom were alive at the time of data collection. Gross-total resection was achieved in 33 (58%) of 57 patients at primary resection. There were no 30-day mortality events following primary and recurrent ependymoma resection. Following primary resection, 6 patients (10%) had posterior fossa syndrome (PFS) and 36 (60%) developed cranial neuropathies, 56% of which recovered within 1 year. One patient (1.7%) required a tracheostomy and 9 patients (15%) required gastrostomy tubes. There were 14 ventriculoperitoneal shunts (23%) inserted for postoperative hydrocephalus. Among recurrent cases, there were 48 recurrent resections performed in 24 patients. Complications included new cranial neuropathy in 10 patients (21%), of which 5 neuropathies resolved within 1 year. There were no cases of PFS following resection of recurrent ependymoma. Gastrostomy tube insertion was required in 3 patients (6.3%), and 1 patient (2.0%) required a tracheostomy. Given the differences in the location of tumor recurrence, a direct comparison between primary and recurrent resection complications was not feasible. Following multivariate analysis adjusting for sex, age, molecular status, and EOR, occurrence of major complications was found to be associated with prolonged LOS but not mortality.

CONCLUSIONS

These results detail the spectrum of postsurgical morbidity following primary and recurrent posterior fossa ependymoma resection. The crude complication rate following resection of infratentorial recurrent ependymoma was lower than that of primary ependymoma, although a statistical comparison revealed no significant differences between the groups. These results should serve to inform providers of the morbidity profile following surgical management of posterior fossa ependymoma and inform perioperative counseling of patients and their families.

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What can a morphometric study of unoperated children teach us about the natural history of metopic synostosis?

Ahmed M. Elawadly, Luke P. J. Smith, Alessandro Borghi, Khaled I. Abdelaziz, Adikarige Haritha Dulanka Silva, David J. Dunaway, Noor Ul Owase Jeelani, Juling Ong, Richard D. Hayward, and Greg James

OBJECTIVE

Outcomes of surgical repair of trigonocephaly are well reported in the literature, but there is a paucity of information on the natural history of unoperated children. The authors evaluated a group of unoperated children with metopic synostosis to describe the natural change in head shape over time.

METHODS

A database was screened for scans of children with unoperated trigonocephaly (2010–2021). Multisuture cases and those with a metopic ridge were excluded. Three-dimensional surface scans (3D stereophotogrammetry/CT) were used for morphological analysis. Nine previously published parameters were used: frontal angle (FA30°), anteroposterior (AP) volume ratio (APVR), AP area ratio (APAR), AP width ratios 1 and 2 (APWR1 and APWR2), and 4 AP diagonal ratios (30° right APDR [rAPDR30], 30° left APDR [lAPDR30], 60° right APDR [rAPDR60], and 60° left APDR [lAPDR60]).

RESULTS

Ninety-seven scans were identified from a cohort of 316 patients with a single metopic suture, in which the male-to-female ratio was 2.7:1. Ages at the time of the scan ranged from 9 days to 11 years and were stratified into 4 groups: group 1, < 6 months; group 2, 6–12 months; group 3, 1–3 years; and group 4, > 3 years. Significant improvements were detected in 5 parameters (APVR, APAR, APWR1, rAPDR30, and lAPDR30) over time, whereas no significant differences were found in FA30, APWR2, rAPDR60, and lAPDR60 between age groups.

CONCLUSIONS

Forehead shape (surface area and volume), as well as narrowing and anterolateral contour at the frontal points, differed significantly over time without surgery. However, forehead angulation, narrowing, and anterolateral contour at temporal points did not show significant differences. This knowledge will aid in surgical and parental decision-making.

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Correlation of the transorbital ultrasonographic optic nerve sheath diameter with intracranial pressure measured intraoperatively in infants with hydrocephalus

Samuel E. Okpara, Enoch O. Uche, Nneka I. Iloanusi, Izuchukwu C. Iloabachie, Wilfred C. Mezue, Ephraim E. Onyia, Mark C. Chikani, and Mesi Mathew

OBJECTIVE

Hydrocephalus is a highly significant global public health concern. In infants, it may be associated with a potentially deleterious increase in intracranial pressure (ICP). Currently, the gold standard for accurate monitoring of ICP is an intraventricular ICP monitor, but this method is invasive and expensive. Transorbital ultrasound measurement of the optic nerve sheath diameter (ONSD) may provide a noninvasive and cost-effective alternative method for monitoring ICP. The goal of the study was to determine the extent of the correlation between ultrasonographic ONSD and ICP in infants.

METHODS

A prospective observational study of 47 children with hydrocephalus aged ≤ 18 months was performed. The ONSD was measured with a transorbital ultrasound scan, while the intraventricular CSF opening pressure was assessed using a manometer during ventriculoperitoneal shunt insertion. Data were analyzed using SPSS software. The ONSD and ICP measurements were correlated, the receiver operating characteristic (ROC) curve was evaluated, and a sensitivity analysis was performed. Inferences were made using the 0.05 alpha level of significance.

RESULTS

The mean age of the study cohort was 4.8 ± 4.3 months, and 93.6% of patients were infants. The mean ONSD was 4.5 ± 0.7 mm (range 2.9–6.0 mm), and the mean ICP was 19.9 ± 6.5 mm Hg (range 5.2–32.4 mm Hg). Both ONSD and ICP increased with increasing age. The Pearson correlation coefficient revealed a strong positive correlation between ONSD and ICP (r = 0.77, p < 0.001). The ONSD cutoff points were 3.2 mm, 4.0 mm, and 4.6 mm for patients with ICPs of 10 mm Hg, 15 mm Hg, and ≥ 20 mm Hg, respectively. The sensitivity of ONSD was 97.7% (area under the ROC curve 0.99), and for every 14.3–mm Hg increase in ICP, the ONSD increased by 1.0 mm holding age constant.

CONCLUSIONS

ONSD has a strong positive correlation with ICP. Correspondingly, ONSD is highly sensitive in estimating ICP.

Free access

Erratum. Letter to the Editor. Intracranial invasive group A streptococcus: importance of culture-independent diagnostics

Gillian Shasby

Open access

The safety and accuracy of intratumoral catheter placement to infuse viral immunotherapies in children with malignant brain tumors: a multi-institutional study

Ariana Barkley, Eric Butler, Christine Park, Allan Friedman, Daniel Landi, David M. Ashley, Darell Bigner, Joshua D. Bernstock, Gregory K. Friedman, James M. Johnston, and Eric M. Thompson

OBJECTIVE

Relatively little is known about the safety and accuracy of catheter placement for oncolytic viral therapy in children with malignant brain tumors. Accordingly, this study combines data from two phase I clinical trials that employed viral immunotherapy across two institutions to describe the adverse event profile, safety, and accuracy associated with the stereotactic placement and subsequent removal of intratumoral catheters.

METHODS

Children with progressive/recurrent supratentorial malignant tumors were enrolled in two clinical trials (NCT03043391 and NCT02457845) and treated with either the recombinant polio:rhinovirus (lerapolturev) or the genetically modified oncolytic herpesvirus (G207). Age, sex, race, tumor diagnosis, and tumor location were analyzed. Events related to the catheter placement or removal were categorized. A catheter that was either pulled back or could not be used was defined as "misplaced." Neuronavigation software was used to analyze the accuracy of catheter placement for NCT03043391. Descriptive statistics were performed.

RESULTS

Nineteen patients were treated across the two completed trials with a total of 49 catheters. The mean ± SD (range) age was 14.1 ± 3.6 (7–19) years. All tumors were grade 3 or 4 gliomas. Nonlobar catheter tip placement included the corpus callosum, thalamus, insula, and cingulate gyrus. Six of 19 patients (31.6%) had minor hemorrhage noted on CT; however, no patients were symptomatic and/or required intervention related to these findings. One of 19 patients had a delayed CSF leak after catheter removal that required oversewing of the surgical site. No patients developed infection or a neurological deficit. In 7 patients with accuracy data, the mean ± SD distance of the planned trajectory (PT) to the catheter tip was 1.57 ± 1.6 mm, the mean angle of the PT to the catheter was 2.43° ± 2.1°, and the greatest distance of PT to the catheter in the parallel plane was 1.54 ± 1.5 mm. Three of 49 (6.1%) catheters were considered misplaced.

CONCLUSIONS

Although instances of minor hemorrhage were encountered, they were clinically asymptomatic. One of 49 catheters required intervention for a CSF leak. Congruent with previous studies in the literature, the stereotactic placement of catheters in these pediatric tumor patients was accurate with approximately 95% of catheters having been adequately placed.

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The etiology of pediatric hydrocephalus across Asia: a systematic review and meta-analysis

Eleanor Ferris, Jacinta Kynaston, David Ulrich Dalle, Yuki Julius Ng, Philomena Leahy, Umar Hassan, and Soham Bandyopadhyay

OBJECTIVE

Despite the high prevalence and significant implications of pediatric hydrocephalus, the etiological distribution of pediatric hydrocephalus across the diverse Asian demographic is poorly understood. This study aimed to inform clinical guidelines and public health decisions by identifying the etiological distribution of pediatric hydrocephalus across Asia.

METHODS

In this systematic review and meta-analysis, the authors searched EMBASE, MEDLINE, CENTRAL, Global Health, Global Index Medicus, and Scopus, with no language restriction, from inception to January 27, 2023. Observational or experimental studies with pediatric data on the causes of hydrocephalus in a country within Asia were included. Pooled proportions of postinfectious hydrocephalus, nonpostinfectious hydrocephalus, and hydrocephalus related to spinal dysraphism were calculated using a random-effects model. Subgroup analyses were performed on prespecified moderators. Methodological study quality was assessed using the modified Newcastle-Ottawa Score and Cochrane’s risk-of-bias tool as per the registered protocol on PROSPERO.

RESULTS

The search yielded 5110 results, for which 79 articles were included, with data on 11,529 children from 18 Asian countries. The pooled proportion of nonpostinfectious hydrocephalus was 29.0% (95% CI 22.9–35.5); postinfectious hydrocephalus was 10.7% (95% CI 7.7–14.1); and hydrocephalus secondary to dysraphism was 7.6% (95% CI 5.1–10.5). The pooled proportion of postinfectious hydrocephalus was greatest in lower-middle-income countries (19.2% [95% CI 12.8–26.3]). There was a negative association between the proportion of postinfectious hydrocephalus and Human Development Index (−1.45 [95% CI −2.21 to −0.69]; p < 0.001); urbanization of the country (−0.008 [95% CI −0.012 to −0.004]; p < 0.001); and increasing distance from the equator (−0.016 [95% CI −0.026 to −0.006]; p = 0.002). The pooled proportion of nonpostinfectious hydrocephalus was greatest in high-income countries (36.7% [95% CI 27.6–46.3]). Certain etiologies of pediatric hydrocephalus were more common in different cultural regions, with postinfectious hydrocephalus most common in South Asia (23.2% [95% CI 15.8–31.5]); nonpostinfectious in East Asia (38.3% [95% CI 26.6–50.7]); and dysraphism in West Asia (11.9% [95% CI 6.4–18.8]).

CONCLUSIONS

Geographic and economic characteristics are associated with the etiological distribution of pediatric hydrocephalus in Asia, with implications for prevention and management strategies. The large proportion of hydrocephalus cases in which the etiology was unclear highlights the need for both improved diagnostics as well as clear and strict universal guidelines on the etiological classification of hydrocephalus.

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Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study

Georgios Mantziaris, Chloe Dumot, Stylianos Pikis, Selcuk Peker, Yavuz Samanci, Gokce D. Ardor, Ahmed M. Nabeel, Wael A. Reda, Sameh R. Tawadros, Khaled Abdel Karim, Amr M. N. El-Shehaby, Reem M. Emad Eldin, Ahmed H. Elazzazi, Darrah Sheehan, Kimball Sheehan, Nuria Martínez Moreno, Roberto Martínez Álvarez, Roman Liscak, Jaromir May, Manjul Tripathi, Akshay Rajput, Narendra Kumar, Rupinder Kaur, Juan Diego Alzate, Douglas Kondziolka, Sam Dayawansa, and Jason P. Sheehan

OBJECTIVE

Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients.

METHODS

This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded.

RESULTS

The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%–14.3%) at 5 years and 23.6% (95% CI 0%–42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic.

CONCLUSIONS

Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.