Evidence of spinal stiffening following fusionless bipolar fixation for neuromuscular scoliosis: a shear wave elastography assessment of lumbar annulus fibrosus.

OBJECTIVES: There are no established criteria for stiffness after fusionless surgery for neuromuscular scoliosis (NMS). As a result, there is no consensus regarding the surgical strategy to propose at long-term follow-up. This study reports the first use of shear wave elastography for assessing the mechanical response of lumbar intervertebral discs (IVDs) after fusionless bipolar fixation (FBF) for NMS and compares them with healthy controls. The aim was to acquire evidence from the stiffness of the spine following FBF. PATIENTS AND METHODS: Nineteen NMS operated on with FBF (18 ± 2y at last follow-up, 6 ± 1 y after surgery) were included prospectively. Preoperative Cobb was 89 ± 20° and 35 ± 1° at latest follow-up. All patients had reached skeletal maturity. Eighteen healthy patients (20 ± 4 y) were also included. Shear wave speed (SWS) was measured in the annulus fibrosus of L3L4, L4L5 and L5S1 IVDs and compared between the two groups. A measurement reliability was performed. RESULTS: In healthy subjects, average SWS (all disc levels pooled) was 7.5 ± 2.6 m/s. In NMS patients, SWS was significantly higher at 9.9 ± 1.4 m/s (p < 0.05). Differences were significant between L3L4 (9.3 ± 1.8 m/s vs. 7.0 ± 2.5 m/s, p = 0.004) and L4L5 (10.3 ± 2.3 m/s vs. 7.1 ± 1.1 m/s, p = 0.0006). No difference was observed for L5S1 (p = 0.2). No correlation was found with age at surgery, Cobb angle correction and age at the SWE measurement. CONCLUSIONS: This study shows a significant increase in disc stiffness at the end of growth for NMS patients treated by FBF. These findings are a useful adjunct to CT-scan in assessing stiffness of the spine allowing the avoidance of surgical final fusion at skeletal maturity.

Prenatal Spina Bifida Repair: Defendable Trespassing of MOMS Criteria Results in Commendable Personalized Medicine.

INTRODUCTION: We hypothesize that after publication of the quintessence of the MOMS trial, eligibility criteria for prenatal spina bifida (SB) repair may be modified if a tenable argumentation underlies this decision. METHODS: Our first 154 fetal surgery patients were analyzed with particular focus on how many, which, and why the original eligibility criteria, set forth by the MOMS Trial Protocol, were disobeyed, and what the eventually detectable, negative and positive impacts of these deviations on outcomes were. RESULTS: A total of 152 patients (2 missing consent) were included (100%). In 69 patients (45.4%), a total of 89 eligibility criteria were disobeyed. In 54 (35.6%) cases, the following maternal criteria were concerned: gestational age at operation of >25+6 weeks in 17 (11.2%), uterine pathologies in 13 (8.6%) women, preoperative BMI ≥35 kg/m2 in 12 (7.9%), previous hysterotomy in 7 (4.6%), previous prematurity in 3 (2%), HIV/hepatitis B in 2 (1.3%), psychosocial issues in 2 (1.3%), and placenta praevia in 1 (0.7%). In 32 (21.1%) cases, fetal criteria were disobeyed 34 times: Fetal anomaly unrelated to SB in 19 (12.5%), no/minimal evidence of hindbrain herniation in 13 (8.6%), and severe kyphosis in 2 (1.3%). We could not identify cases where non-observation of criteria led to clear-cut maternal and/or fetal disadvantages. CONCLUSION: This study shows that MOMS trial eligibility criteria for prenatal SB repair should be modified or even abandoned with adequate medical and ethical argumentation, and with written parental informed consent after non-directive, full disclosure counseling. This clear-cut change of paradigm is a necessity as it leads toward personalized medicine, allowing more fetuses to benefit from fetal surgery than would have benefitted with the former, published, MOMS criteria in place.

Doublecortin and Glypican-2 concentrations in the cerebrospinal fluid from infants are developmentally downregulated.

OBJECTIVE: Doublecortin (DCX) and glypican-2 (GPC2) are neurodevelopmental proteins involved in the differentiation of neural stem/progenitor cells (NSPCs) to neurons, and are developmentally downregulated in neurons after birth. In this study, we investigated whether the concentrations of DCX and GPC2 in the cerebrospinal fluid (CSF) from human pediatric patients reflect this developmental process or are associated with cerebral damage or inflammatory markers. METHODS: CSF was collected from pediatric patients requiring neurosurgical treatment. The concentrations of DCX, GPC2, neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-γ, and TNF-⍺) were measured using immunoassays. RESULTS: From March 2013 until October 2018, 63 CSF samples were collected from 38 pediatric patients (20 females; 17 patients with repeated measurements); the median term born-adjusted age was 3.27 years [Q1: 0.31, Q3: 7.72]. The median concentration of DCX was 329 pg/ml [Q1: 192.5, Q3: 1179.6] and that of GPC2 was 26 pg/ml [Q1: 13.25, Q3: 149.25]. DCX and GPC2 concentrations independently significantly associated with age, and their concentration declined with advancing age, reaching undetectable levels at 0.3 years for DCX, and plateauing at 1.5 years for GPC2. Both DCX and GPC2 associated with hydrocephalus, NSE, IL-1ß, IL-2, IL-8, IL-13. No relationship was found between sex, acute infection, S100B, IL-4, IL-6, IL-10, IFN-γ, TNF-α and DCX or GPC2, respectively. CONCLUSIONS: Concentrations of DCX and GPC2 in the CSF from pediatric patients are developmentally downregulated, with the highest concentrations measured at the earliest adjusted age, and reflect a neurodevelopmental stage rather than a particular disease state.

Wound closure with a mesh and liquid tissue adhesive (Dermabond Prineo) system in pediatric spine surgery: a prospective single-center cohort study incorporating parent-reported outcome measures.

OBJECTIVE: Wound healing can be challenging in children undergoing spine surgery for neurological conditions due to a high risk of cerebrospinal fluid (CSF) leakage and wound infection. In adults, use of the Dermabond Prineo (DP) skin closure system, which consists of both tissue adhesive glue and a self-adhesive mesh, for wound closure of medium-length surgical incisions has been reported. The aim of this study was to investigate the efficiency and cosmetic outcome of DP for wound closure in extra- and intradural pediatric neurological spine surgery. METHODS: In this prospective cohort study, 47 children underwent 50 spine procedures using DP for wound closure between 2018 and 2022 at a single institution. Patient demographic and surgical data were collected. The primary outcome was revision surgery for wound healing disorders, while secondary outcomes were infections, minor wound healing disorders, and both physician and parental satisfaction (parent-reported outcome measures [PROMs]) at last follow-up. RESULTS: Among 50 spinal (45 intra- and 5 extradural) interventions, 1 patient (2%) underwent revision surgery for a cutaneous CSF fistula and pseudomeningocele. Minor wound healing disorders occurred after 16 surgeries, which did not require surgical wound revision and resolved completely. No allergic reactions to DP or surgical site infections within 30 days were observed. The parents and the medical team described wound care as significantly facilitated since wound dressing changes were not needed. Three families (6.4%) encountered difficulties in wound care, and 46 (97.9%) were satisfied with DP. The cosmetic outcome based on PROMs was excellent, with a mean score of 8 (IQR 2) on a scale from 1 to 10. At long-term follow-up, a mean of 11.3 ± 10.7 months after surgery, physicians rated the cosmetic outcome on the visual analog scale (median score 9, IQR 1) and Hollander scale (median score 6, IQR 1). The outcomes were similar among the different pathologies and age groups and did not differ in patients with and without syndromic malformations. CONCLUSIONS: The application of DP is simple, enables good patient comfort, facilitates both professional and parental wound care, and leads to excellent cosmetic results. DP possibly aids in the reduction of postoperative CSF leakage and infections after pediatric neurological spine surgery.

Is the Choroid Plexus Needed?

BACKGROUND: Choroid plexectomy was first performed around 1910. Later, the technique evolved into subtotal choroid plexus cauterization (CPC) but was largely abandoned following the invention of the ventriculoperitoneal shunt. Over time, with improved understanding of the pathophysiology of hydrocephalus and improvement in endoscopic techniques and equipment, the procedure of CPC was reintroduced. However, little is known about the biomolecular consequences of ablation of a significant portion of the choroid plexus on metabolic brain homeostasis, neurogenesis, and neuroimmunology. SUMMARY: The physiological functions of choroid plexus in neurogenesis and neuroimmunology and its role in diseases, such as AD and MS, should alert to possible as yet to be determined consequences. Studies, both in children and in adults, are needed not only on the success in hydrodynamic stabilization of hydrocephalus but also on the long-term outcome, especially premature neurodegeneration and inflammatory changes and on compensatory metabolic mechanisms. KEY MESSAGES: The value of CPC for treatment of hydrocephalus in medically underserved areas should be remembered, yet when alternative treatment options are available, we cannot responsibly advocate against or for the use of CPC. Therefore, perhaps a more detailed discussion of risks and benefits of a CPC with parents would be best to include the possible implications in brain development and function.

Temporosylvian arachnoid cysts in children. Part 2: Postoperative neuropsychological and clinical improvement.

OBJECTIVE: The authors' objective was to study clinical, imaging, and neuropsychological changes in children who underwent surgery for a temporal arachnoid cyst (TAC). METHODS: Thirty-four children were prospectively assessed similarly at diagnosis and postoperatively (mean 14 months) with clinic visits, images, cognitive tests, and parental questionnaires on mood/behavior and executive functions. The scores were compared pre- and postoperatively for the entire cohort and individually. The scores of 25 children were also compared with a control group of 23 healthy age-matched children. Parents were administered an outcome questionnaire on average 4 years postoperatively. RESULTS: The 34 children selected for surgery had signs of raised intracranial pressure (74%) and/or selective neuropsychological disorders presumably linked to cyst location (learning difficulties in 65%, cognitive difficulties in 56%, and mood/behavior difficulties in 47%). The majority of patients had a convex cyst (85%) and underwent microsurgical fenestration (85%). The TAC volume decreased ≥ 50% for 59% of children. On the Wechsler Intelligence Scale, the entire cohort significantly improved on Full Scale IQ and verbal and perceptual nonverbal indexes. Individually, nearly half of the children (47%) highly increased their scores (≥ 15 points) on at least one IQ index and 26% on at least two indexes. Language, working memory, episodic memory, and executive functions were also significantly improved. Improvements were more pronounced in patients with a preoperative heterogeneous profile with isolated lower scores and a left-sided cyst. Parental questionnaires showed reduction in anxiety, aggressiveness, social problems, and daily life executive disorders. Preschool-aged children improved significantly in language and verbal IQ, as did middle/high school-aged children in many domains. Individual analyses revealed improvement in 76% of cases. Cognitive scores were lower for patients preoperatively than for controls and were no longer significantly different postoperatively in verbal fluency, visual memory, and working memory. Four years later, 97% of parents described an improvement in their child, correlated with cognitive improvements. CONCLUSIONS: Among children with a TAC, some have no clinical signs or neuropsychological difficulties, and others may show signs of raised intracranial pressure and/or specific neuropsychological disorders that impact daily life and require significant and long-lasting rehabilitation. In these cases, consideration may be given to surgical decompression. It is interesting to note that 76% of this surgically treated cohort improved regardless of the child's age, particularly in patients with selective disorders and an impact on daily life. However, a larger number of children will need to be investigated before the true benefit of such treatment can be known.

Temporosylvian arachnoid cysts in children. Part 1: Cognitive profile of children with a temporal cyst and impact of the cyst in daily life. A prospective study in 100 consecutive children.

OBJECTIVE: The aim of this study was to determine the cognitive profile of children with a temporal arachnoid cyst (TAC) and its impact on daily life. METHODS: The authors prospectively analyzed the cognitive and psychological profiles of 100 consecutive children relative to age and cyst characteristics (side, cyst size, and cyst shape: convex or nonconvex) and their outcome 4 years later. RESULTS: Mean IQs were normal but with high heterogeneity on Full Scale IQ (FSIQ; range 59-150); 29% of children had at least one Wechsler index below the norm, in particular, Processing Speed and Working Memory Indexes. Impairments were observed in language for 31% of children, as well as in verbal memory (28%), visual memory (23%), executive function (21%), and visual attention (24%). Half of the children (50%) needed rehabilitation for learning difficulties, and 26% had academic difficulties. The parental questionnaire BRIEF (Behavior Rating Inventory of Executive Function) revealed significant executive dysfunctions in daily life for 22% of the children. One-third of the patients (34%) required psychotherapy for anxiety or social disorders, with higher rates in patients with a right-sided cyst and older children. Cyst size had very little neuropsychological impact. Convex cysts were significantly associated with worse performance than nonconvex cysts on all Wechsler indexes and FSIQ, and in language, verbal memory, attention, and visuospatial skills. Children with a convex cyst had significantly more executive and behavior difficulties in daily life and more psychotherapy than other children. The effect of cyst shape was independent of Galassi type and cyst side. Children with a ruptured cyst or an incidentally discovered cyst usually had a good cognitive level. Four years later, children without initial disorders remained stable, whereas those with difficulties who did not undergo surgery needed more rehabilitation and school adaptations. CONCLUSIONS: This large cohort study revealed a varied profile of children with a TAC: at initial assessment, 50% had neuropsychological difficulties and needed rehabilitation and/or psychotherapy for learning or behavior difficulties, and 50% had no difficulties, which may explain the debate about this pathology. Patients with neuropsychological difficulties had a heterogeneous profile with normal intelligence but selective cognitive and/or behavior disorders that may have a long-term impact on their quality of life, particularly those with a right-sided cyst. A neuropsychological evaluation is not always necessary for a cyst discovered incidentally, but early evaluation is essential in patients with academic, learning, or psychological disorders. When assessment shows selective disorders presumably linked to cyst location, surgery may be considered, particularly for convex cysts, as this study revealed more effects in association with cyst shape than with cyst size and significantly poorer performance with a convex cyst.

Scaphocephaly and increased intra-cranial pressure in non-operated adults: A controlled anthropological study on 21 skulls.

AIM AND SCOPE: The prevalence of increased intra-cranial pressure (ICP) in patients with scaphocephaly is controversial. Here, based on anthropological material, we aimed to determine whether adults with non-operated sagittal synostosis show indirect signs of increased ICP. MATERIALS AND METHODS: Thirty-eight dry skulls (21 skulls with sagittal craniosynostosis and 17 controls) were selected from the collections of the National Museum of Natural History (Paris, France). All skulls registered as 'fused sagittal suture' or 'scaphocephaly' in the registry of the Museum were included. All had total fusion of the sagittal suture. Controls were selected within skulls of similar origin (France), without visible craniofacial anomalies. The 38 skulls were CT-scanned using a standard medical CT-scan with a protocol dedicated to dry bone imaging. Eight radiological signs associated with raised ICP were assessed: (1) calvaria and (2) skull base thinning, (3) dorsum sellae erosion, (4) sella turcica lengthening, (5) copper beaten skull, (6) suture diastasis, (7) persistent metopic suture, and (8) small frontal sinus. Scaphocephaly was assessed based on head circumference, cranial index, intra-cranial volume, fronto-nasal angle, and inter-zygomatic distance. Linear and non-linear logistic models were used to compare groups. RESULTS: 19/21 skulls with sagittal synostosis were significantly scaphocephalic. None of the criteria for ICP were significantly different in skulls with scaphocephaly relative to controls. Nevertheless, 5 individual skulls with scaphocephaly had ≥ 3 signs in favor of a history of raised ICP. We do not report the significant prevalence of indirect signs of raised ICP in adults with scaphocephaly. These results do not allow ruling out a history of early raised ICP or of minor prolonged raised ICP. Even though our findings support the fact that scaphocephaly is not significantly associated with prolonged raised ICP, individual cases (5/21) with clear signs in favor of a history of brain compression indicate that scaphocephaly correction should be considered as a functional procedure until the production of clear evidence. Cognitive assessments of non-operated adult patients with scaphocephaly could contribute to tackle this recurring question in craniofacial surgery.

Arterial Spin Labeling for the Etiological Workup of Intracerebral Hemorrhage in Children.

BACKGROUND AND PURPOSE: Pediatric nontraumatic intracerebral hemorrhage accounts for half of stroke in children. Early diagnostic of the causative underlying lesion is the first step toward prevention of hemorrhagic recurrence. We aimed to investigate the performance of arterial spin labeling sequence (ASL) in the acute phase etiological workup for the detection of an arteriovenous shunt (AVS: including malformation and fistula), the most frequent cause of pediatric nontraumatic intracerebral hemorrhage. METHODS: Children with a pediatric nontraumatic intracerebral hemorrhage between 2011 and 2019 enrolled in a prospective registry were retrospectively included if they had undergone ASL-magnetic resonance imaging before any etiological treatment. ASL sequences were reviewed using cerebral blood flow maps by 2 raters for the presence of an AVS. The diagnostic performance of ASL was compared with admission computed tomography angiography, other magnetic resonance imaging sequences including contrast-enhanced sequences and subsequent digital subtraction angiography. RESULTS: A total of 121 patients with pediatric nontraumatic intracerebral hemorrhage were included (median age, 9.9 [interquartile range, 5.8-13]; male sex 48.8%) of whom 76 (63%) had a final diagnosis of AVS. Using digital subtraction angiography as an intermediate reference, visual ASL inspection had a sensitivity and a specificity of, respectively, 95.9% (95% CI, 88.5%-99.1%) and 79.0% (95% CI, 54.4%-94.0%). ASL had a sensitivity, specificity, and accuracy of 90.2%, 97.2%, and 92.5%, respectively for the detection of the presence of an AVS, with near perfect interrater agreement (κ=0.963 [95% CI, 0.912-1.0]). The performance of ASL alone was higher than that of other magnetic resonance imaging sequences, individually or combined, and higher than that of computed tomography angiography. CONCLUSIONS: ASL has strong diagnostic performance for the detection of AVS in the initial workup of intracerebral hemorrhage in children. If our findings are confirmed in other settings, ASL may be a helpful diagnostic imaging modality for patients with pediatric nontraumatic intracerebral hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: 3618210420, 2217698.

Pediatric brain arteriovenous malformation recurrence: a cohort study, systematic review and meta-analysis.

BACKGROUND: Recurrence following obliteration of brain arteriovenous malformations (AVMs) is common in children surgically treated, but recurrences following endovascular (EVT) and radiosurgical approaches are scantily reported. OBJECTIVE: To analyze the rates and risk factors for AVM recurrence after obliteration in a single-center cohort of children with ruptured AVMs treated with multimodal approaches, and to carry out a comprehensive review and meta-analysis of current data. METHODS: Children with ruptured AVMs between 2000 and 2019 enrolled in a prospective registry were retrospectively screened and included after angiographically determined obliteration to differentiate children with/without recurrence. A complementary systematic review and meta-analysis of studies investigating AVM recurrence in children between 2000 and 2020 was aggregated to explore the overall recurrence rates across treatment modalities by analyzing surgery versus other treatments. RESULTS: Seventy children with obliterated AVMs were included. AVM recurrences (n=10) were more commonly treated with EVT as final treatment (60% in the recurrence vs 13.3% in the no-recurrence group, p=0.018). Infratentorial locations were associated with earlier and more frequent recurrences (adjusted relative risk=4.62, 95% CI 1.08 to 19.04; p=0.04).In the aggregate analysis, the pooled rate of AVM recurrence was 10.9% (95% CI 8.7% to 13.5%). Younger age at presentation was associated with more frequent recurrences (RR per year increase, 0.97, 95% CI 0.93 to 0.99; p=0.046). CONCLUSION: Location of infratentorial AVMs and younger age at presentation may be associated with earlier and more frequent recurrences. The higher rates of recurrence in patients with AVMs obliterated with EVT questions its role in an intent-to-cure approach and reinforces its position as an adjunct to surgery and/or radiosurgery.

Mortality and functional outcome after pediatric intracerebral hemorrhage: cohort study and meta-analysis.

OBJECTIVE: The clinical outcome of pediatric intracerebral hemorrhage (pICH) is rarely reported in a comprehensive way. In this cohort study, systematic review, and meta-analysis of patients with pICH, the authors aimed to describe the basic clinical outcomes of pICH. METHODS: Children who received treatment for pICH at the authors' institution were prospectively enrolled in the cohort in 2008; data since 2000 were retrospectively included, and data through October 2019 were analyzed. The authors then searched PubMed and conducted a systematic review of relevant articles published since 1990. Data from the identified populations and patients from the cohort study were pooled into a multicategory meta-analysis and analyzed with regard to clinical outcomes. RESULTS: Among 243 children screened for inclusion, 231 patients were included. The median (IQR) age at ictus was 9.6 (4.6-12.5) years, and 128 patients (53%) were male. After a median (IQR) follow-up of 33 (13-63) months, 132 patients (57.4%) had a favorable clinical outcome, of whom 58 (44%) had no residual symptoms. Nineteen studies were included in the meta-analysis. Overall, the proportion of children with complete recovery was 27% (95% CI 19%-36%; Q = 49.6; I2 = 76%); of those with residual deficits, the complete recovery rate was 48.1% (95% CI 40%-57%; Q = 75.3; I2 = 81%). When pooled with the cohort study, the aggregate case-fatality rate at the last follow-up was 17.3% (95% CI 12%-24%; Q = 101.6; I2 = 81%). CONCLUSIONS: Here, the authors showed that 1 in 6 children died after pICH, and the majority of children had residual neurological deficits at the latest follow-up. Results from the cohort study also indicate that children with vascular lesions as the etiology of pICH had significantly better clinical functional outcomes.

Hemorrhage Expansion After Pediatric Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Significant hemorrhage expansion (sHE) is a known predictor of poor outcome after an intracerebral hemorrhage (ICH) in adults but remains poorly reported in children. In a large inception cohort, we aimed to explore the prevalence of sHE, its associations with clinical outcomes, and its clinical-imaging predictors in children. METHODS: Children admitted between January 2000 and March 2020 at a quaternary care pediatric hospital were screened for inclusion. Sample was restricted to children with 2 computed tomography scans within 72 hours of ICH onset, and a minimal clinical follow-up of months. sHE was defined as an increase from baseline ICH volume by 6 cc or 33% on follow-up computed tomography. Clinical outcome was assessed at 12 months with the King's Outcome Scale for Childhood Head Injury score and defined as favorable for scores ≥5. RESULTS: Fifty-two children met inclusion criteria, among which 8 (15%) demonstrated sHE, and 18 (34.6%) any degree of expansion. Children with sHE had more frequent coagulation disorders (25.0% versus 2.3%; P=0.022). After multivariable adjustment, only the presence of coagulation disorders at baseline remained independently associated with sHE (adjusted odds ratio, 14.4 [95% CI, 1.04-217]; P=0.048). sHE was independently associated with poor outcome (King's Outcome Scale for Childhood Head Injury <5A, odds ratio, 5.77 [95% CI, 1.01-38.95]; P=0.043). CONCLUSIONS: sHE is a frequent phenomenon after admission for a pediatric ICH and more so in children with coagulation defects. As sHE was strongly associated with poorer clinical outcomes, these data mandate a baseline coagulation work up and questions the need for protocolized repeat head computed tomography in children admitted for pediatric ICH.

Etiology of intracerebral hemorrhage in children: cohort study, systematic review, and meta-analysis.

OBJECTIVE: Understanding the etiological spectrum of nontraumatic pediatric intracerebral hemorrhage (pICH) is key to the diagnostic workup and care pathway. The authors aimed to evaluate the etiological spectrum of diseases underlying pICH. METHODS: Children treated at the authors' institution for a pICH were included in an inception cohort initiated in 2008 and retrospectively inclusive to 2000, which was analyzed in October 2019. They then conducted a systematic review of relevant articles in PubMed published between 1990 and 2019, identifying cohorts with pICH. Identified populations and patients from the authors' cohort were pooled in a multicategory meta-analysis. RESULTS: A total of 243 children with pICH were analyzed in the cohort study. The final primary diagnosis was an intracranial vascular lesion in 190 patients (78.2%), a complication of a cardiac disease in 17 (7.0%), and a coagulation disorder in 14 (5.8%). Hematological and cardiological etiologies were disproportionately more frequent in children younger than 2 years (p < 0.001). The systematic review identified 1309 children in 23 relevant records pooled in the meta-analysis. Overall, there was significant heterogeneity. The dominant etiology was vascular lesion, with an aggregate prevalence of 0.59 (95% CI 0.45-0.64; p < 0.001, Q = 302.8, I2 = 92%). In 18 studies reporting a detailed etiological spectrum, arteriovenous malformation was the dominant etiology (68.3% [95% CI 64.2%-70.9%] of all vascular causes), followed by cavernoma (15.7% [95% CI 13.0%-18.2%]). CONCLUSIONS: The most frequent etiology of pICH is brain arteriovenous malformation. The probability of an underlying vascular etiology increases with age, and, conversely, hematological and cardiac causes are dominant causes in children younger than 2 years.

Acute surgical management of children with ruptured brain arteriovenous malformation.

OBJECTIVE: Rupture of brain arteriovenous malformation (AVM) is the main etiology of intracerebral hemorrhage (ICH) in children. Ensuing intracranial hypertension is among the modifiable prognosis factors and sometimes requires emergency hemorrhage evacuation (HE). The authors aimed to analyze variables associated with HE in children with ruptured AVM. METHODS: This study was a single-center retrospective analysis of children treated for ruptured AVM. The authors evaluated the occurrence of HE, its association with other acute surgical procedures (e.g., nidal excision, decompressive hemicraniectomy), and clinical outcome. Variables associated with each intervention were analyzed using univariable and multivariable models. Clinical outcome was assessed at 18 months using the ordinal King's Outcome Scale for Childhood Head Injury. RESULTS: A total of 104 patients were treated for 112 episodes of ruptured AVM between 2002 and 2018. In the 51 children (45.5% of cases) who underwent HE, 37 procedures were performed early (i.e., within 24 hours after initial cerebral imaging) and 14 late. Determinants of HE were a lower initial Glasgow Coma Scale score (adjusted odds ratio [aOR] 0.83, 95% CI 0.71-0.97 per point increase); higher ICH/brain volume ratio (aOR 18.6, 95% CI 13-26.5 per percent increase); superficial AVM location; and the presence of a brain herniation (aOR 3.7, 95% CI 1.3-10.4). Concurrent nidal surgery was acutely performed in 69% of Spetzler-Martin grade I-II ruptured AVMs and in 25% of Spetzler-Martin grade III lesions. Factors associated with nidal surgery were superficial AVMs, late HE, and absent alteration of consciousness at presentation. Only 8 cases required additional surgery due to intracranial hypertension. At 18 months, overall mortality was less than 4%, 58% of patients had a favorable outcome regardless of surgical intervention, and 87% were functioning independently. CONCLUSIONS: HE is a lifesaving procedure performed in approximately half of the children who suffer AVM rupture. The good overall outcome justifies intensive initial management.

Hydrocephalus in children with ruptured cerebral arteriovenous malformation.

OBJECTIVE: Hydrocephalus is a strong determinant of poor neurological outcome after intracerebral hemorrhage (ICH). In children, ruptured brain arteriovenous malformations (bAVMs) are the dominant cause of ICH. In a large prospective cohort of pediatric patients with ruptured bAVMs, the authors analyzed the rates and predictive factors of hydrocephalus requiring acute external ventricular drainage (EVD) or ventriculoperitoneal shunt (VPS). METHODS: The authors performed a single-center retrospective analysis of the data from a prospectively maintained database of children admitted for a ruptured bAVM since 2002. Admission clinical and imaging predictors of EVD and VPS placement were analyzed using univariate and multivariate statistical models. RESULTS: Among 114 patients (mean age 9.8 years) with 125 distinct ICHs due to ruptured bAVM, EVD and VPS were placed for 55/125 (44%) hemorrhagic events and 5/114 patients (4.4%), respectively. A multivariate nominal logistic regression model identified low initial Glasgow Coma Scale (iGCS) score, hydrocephalus on initial CT scan, the presence of intraventicular hemorrhage (IVH), and higher modified Graeb Scale (mGS) score as strongly associated with subsequent need for EVD (all p < 0.001). All children who needed a VPS had initial hydrocephalus requiring EVD and tended to have higher mGS scores. CONCLUSIONS: In a large cohort of pediatric patients with ruptured bAVM, almost half of the patients required EVD and 4.4% required permanent VPS. Use of a low iGCS score and a semiquantitative mGS score as indicators of the IVH burden may be helpful for decision making in the emergency setting and thus improve treatment.

Dizygotic opposite-sex twins with surgically repaired concordant myelomeningocele conceived by in vitro fertilization using intracytoplasmic sperm injection: a case report and review of the literature.

BACKGROUND: Myelomeningocele (MMC) is a common subtype of congenital neural tube defects (NTD). Although congenital malformations including NTD are more common in twins, concordance, especially in dizygotic twins, is extremely rare and is found mostly in same-sex twins. The role of genetic and environmental factors in the etiology of MMC is unclear. CASE REPORT: Dizygotic twins of opposite sex were born at term to a 35-year-old woman conceived with in vitro fertilization (IVF) using intracytoplasmic sperm injection (ICSI). Prenatal ultrasonography (US) revealed concordant lumbosacral MMC at 18 weeks of gestation as well as ventriculomegaly and Arnold-Chiari malformation type II at 28 weeks. Both twins underwent surgical repair of the MMC within 48 h after birth and required a ventriculoperitoneal shunt in the second week of life. DISCUSSION: The case presented raises questions concerning the etiology of MMC, since in twins, it is compelling to attribute the etiology to genetic factors. In the literature, 22 pairs of twins with concordant MMC have been reported, and of the 10 dizygotic twins described, four were of opposite sex. However, in monozygotic twins, most of the cases are non-concordant; therefore, the role of genetics remains unclear. In addition, environmental factors such as nutrition, metabolic folic acid deficiency, and assisted conception with IVF and ICSI might play a role as well. CONCLUSION: The appearance of concordant MMC in opposite-sex dizygotic twins, conceived by IVF using ICSI, intrigues questions concerning the etiology of MMC. In such cases, genetic counseling and evaluation should be considered.

Outcome of Spinal Surgery in Patients Older Than Age 90 Years.

BACKGROUND: Increased life expectancy has led to indications for spine surgery in patients older than 90 years, but data on associated risks and outcome are lacking. METHODS: Indication, type of surgery, complications, functional outcome, and mortality were retrospectively collected from all patients aged 90 years or older operated between 2006 and 2016 at the University Hospital Basel, Switzerland. RESULTS: Sixty-nine patients were included, of which 55% had degenerative, 36% traumatic, and 9% other pathologies. Most surgeries (84%) were performed electively and 16% as emergencies. More than a third (36%) of elective and 58% of emergency surgeries required stabilization. The complication rate was 54% in the elective surgery group (ELSG) and 125% in the emergency surgery group (EMSG). Stabilization (P = 0.006) and emergency surgeries (P = 0.032) were significant risk factors for experiencing complications. Six weeks after surgery, 80% of the patients reported symptomatic improvement. More than half (58%) of the patients in the ELSG reached their specific median life expectancy, compared with 38% in the EMSG. Seventeen percent of patients in the EMSG versus 0% in the ELSG died in the first 3 months after surgery. In the nonstabilized group, 67% of the patients reached their median life expectancy, compared with 38% of the stabilized group. CONCLUSIONS: Elective spinal surgery in patients older than 90 years of age does not reduce life expectancy and has a good functional outcome for well-selected patients, whereas emergency surgery and stabilization surgery in this age group are associated with a high rate of complications and higher mortality.

Intraoperative unfolding and postoperative pruning of the pituitary gland after transsphenoidal surgery for pituitary adenoma: A volumetric and endocrinological evaluation.

PURPOSE: To describe the volumetric changes that the pituitary gland (PG) undergoes during and after transsphenoidal surgery (TSS), and to evaluate if unfolding and/or pruning are related to endocrinological outcome measures. METHODS: Retrospective evaluation of data prospectively collected of a cohort of patients undergoing TSS for a pituitary adenoma with the adjunctive use of high field 3 Tesla intraoperative MRI. All patients underwent a full endocrinological workup preoperatively, as well as at 6 weeks and 1 year postoperatively. A decrease in PG volume ≥15% between the intraoperative and 3-month, or between the 3-month and 12-month measurements, was considered early and late pruning, respectively. RESULTS: The PG unfolds significantly during TSS, and subsequently undergoes pruning up until 1 year postoperatively, in most cases returning to the preoperatively measured PG volume. A smaller baseline PG volume predicts intraoperative unfolding. Early pruning of the PG after surgery was associated with new functional deficits. Baseline pituitary compression also correlated to newly occurring deficits after surgery. A larger 1-year pituitary volume was associated with biochemical remission in secreting adenomas. CONCLUSIONS: The PG shows dynamic change during and after TSS for pituitary adenoma. Small baseline and 3-month PG volumes, as well as early pruning were independently associated with new deficits. Our findings warrant prospective validation in a larger cohort with higher statistical power.

Brain-resident microglia predominate over infiltrating myeloid cells in activation, phagocytosis and interaction with T-lymphocytes in the MPTP mouse model of Parkinson disease.

Parkinson disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra (SN). Recent evidence suggests that innate and adaptive immune responses can influence dopaminergic cell death in animal models of PD. However, the precise role of mononuclear phagocytes, key players in damaged tissue clearance and cross-talk with cells of adaptive immune system, remains open in PD. Mononuclear phagocytes in the brain occur as brain-resident microglia and as brain-infiltrating myeloid cells. To elucidate their differential contribution in the uptake of dopaminergic cell debris and antigen presentation capacity, we labeled nigral dopaminergic neurons retrogradely with inert rhodamine-conjugated latex retrobeads before inducing their degeneration by subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. We used green fluorescent protein (GFP)-expressing bone marrow chimeric mice to differentiate brain-infiltrating from brain-resident myeloid cells. We found that half of both endogenous (GFP-) and exogenous (GFP+) microglia (Iba1+) in the SN incorporated the tracer from degenerating dopaminergic neurons 1d after MPTP intoxication. In absolute numbers, endogenous microglia were much more activated to macrophages compared to exogenous myeloid cells at 1d after MPTP. Mainly the endogenous, tracer-phagocytosing microglia expressed the major histocompatibility complex (MHC) class II molecule for antigen presentation. Additionally, T-lymphocytes (Iba1-/GFP+/CD3+), which infiltrate the MPTP-lesioned SN, were mainly in direct contact with MHCII+ endogenous microglia. Our data suggest that brain-resident microglia are predominantly implicated in the removal of dopaminergic cell debris and the cross-talk with infiltrating T-lymphocytes in the SN in the MPTP mouse model of PD.