Laser interstitial thermal therapy is effective and safe for the treatment of brain tumors in NF1 patients after cerebral revascularization for moyamoya angiopathy: a report on two cases

BackgroundThe co-occurrence of moyamoya vasculopathy and extra-optic pathway tumors is rare in neurofibromatosis type 1 (NF1), with only four cases described in the literature. Brain surgery in these patients may be challenging because of the risk of brain infarction after skin and dural incision. Given its percutaneous and minimally invasive nature, laser interstitial thermal therapy (LITT) is an ideal option for the treatment of brain tumors in these patients. Here, we report on two patients with NF1 and moyamoya syndrome (MMS) treated for a brain glioma with LITT, after cerebral revascularization.CasesThe first patient, with familial NF1, underwent bilateral indirect revascularization with multiple burr holes (MBH) for symptomatic MMS. Two years later, she was diagnosed with a left temporal tumor, with evidence of radiologic progression over 10 months. The second patient, also with familial NF1, developed unilateral MMS when he was 6 years old and was treated with MBH. At the age of 15 years, MRI showed a right cingular lesion, growing on serial MRIs. Both patients underwent LITT with no perioperative complications; they are progression free at 10 and 12 months, respectively, and the tumors have decreased in volume.DiscussionWhile the association of extra-optic neoplasm and moyamoya angiopathy is seldom reported in NF1, tumor treatment is challenging in terms of both avoiding stroke and achieving oncological control. Here, we show in 2 cases, that LITT could be a safe and effective option in these rare conditions

Dejerine-Roussy syndrome

On June 7, 1906, Jules Dejerine (1849–1917) and Gustave Roussy (1874–1948) presented to the Société de Neurologie de Paris the first description of the thalamic syndrome with serial-section microscopic images. They also provided the first account of central poststroke pain (CPSP). They suggested that pain is one of the primary symptoms of the syndrome, although one of their own patients (“Hud”) did not have pain. Several contemporary studies have highlighted the involvement of the anterior part of the pulvinar (PuA) in patients with CPSP of thalamic origin. Two historical observations (cases Jos and Hud) are reviewed here using the Morel nuclei staining atlas (2007). Dejerine and Roussy proposed the “irritative theory” to explain CPSP of thalamic origin and, in line with the most recent literature, they invoked the involvement of the PuA. When matching images for the Jos and Hud cases with the Morel atlas, it appears that the lesions involved what Dejerine then termed the noyau externe; that is, the ventral posterolateral nucleus and the PuA. In the Jos case, the lesion extended medially to what Dejerine termed the noyau médian de Luys; that is, the central medial–parafascicular nuclei, whereas in the Hud case the lesion extended more inferiorly. From the finding in the Hud case, one can hypothesize that impairment of the PuA alone does not assure pain. The work of Dejerine and Roussy, based on clinico-anatomical correlations, remains relevant to this day

Pediatric brainstem cavernous malformations: 2-center experience in 40 children

OBJECTIVE Brainstem cavernous malformations (BSCMs) are relatively uncommon, low-flow vascular lesions in children. Given the paucity of data, guidelines regarding the clinical management of BSCMs in children are lacking and the surgical indication is most commonly based on an individual surgeon's judgment and experience. The goal in this study was to evaluate the clinical behavior of BSCMs in childhood and the long-term outcome in children managed conservatively and surgically. METHODS This was an observational, retrospective study including all children with BSCMs who were followed at 2 institutions between 2008 and 2020. RESULTS The study population consisted of 40 children (27 boys, 67.5%) with a mean age of 11.4 years. Twenty-three children (57.5%) were managed conservatively, whereas 17 children (42.5%) underwent resection of BSCMs. An aggressive clinical course was observed in 13 children (32.5%), who experienced multiple hemorrhages with a progressive pattern of neurological decline. Multiple BSCMs were observed in 8 patients, of whom 3 patients presented with a complex of multiple tightly attached BSCMs and posed a significant therapeutic challenge. The overall long-term outcome was favorable (modified Rankin Scale [mRS] scores 0-2) in 36 patients (90%), whereas an unfavorable outcome (mRS scores 3 and 4) was seen in 4 children (10%). An mRS score of 5 or 6 was not observed. The mean (± SD) follow-up was 88.0 (± 92.6) months. CONCLUSIONS The clinical course of BSCMs in children is highly variable, with benign lesions on the one hand and highly aggressive lesions with repetitive hemorrhages on the other. Given the greater life expectancy and the known higher functional recovery in children, surgical treatment should be considered early in young patients presenting with surgically accessible lesions and an aggressive clinical course, and it should be performed in a high-volume center

Hydrocephalus in children with ruptured cerebral arteriovenous malformation

International audienceObjective: 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

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

Rare coding variants in CTSO , a potential new actor of arterial remodeling, are associated to familial intracranial aneurysm

Background Intracranial aneurysm (IA) is a common cerebrovascular abnormality characterized by localized dilation and wall thinning in intracranial arteries, that frequently leads to fatal vascular rupture. The mechanisms underlying IA formation, growth and rupture are mostly unknown, and while increasing evidence suggest a genetic component of IA, identification of specific genes or causal molecular pathways remains largely inconclusive and only a small fraction of the risk attributable to genetics for IA in the general population. Methods: Here, we combined whole exome sequencing and identity-by -descent analyses with functional investigations to identify rare IA predisposing variants in familial forms of IA and understand their contribution to the pathophysiology of IA. Results We identified two rare missense variants in the CTSO gene shared by all the affected relatives in two large pedigrees with multiple IA-affected relative. CTSO encodes for the cysteine-type papain-like cathepsin CTSO. Functional analyses revealed that CTSO acts as an extracellular protease controlling vascular smooth muscle cell migration and adhesion to the extracellular matrix. CTSO depletion, as well as expression of the two CTSO variants, which were poorly secreted, led to increase the amount of fibronectin. This effect is associated with a marked increase in VSMC stiffness which was rescued by exogenous CTSO. Conclusions This report identifies rare CTSO variants in familial IA patients and suggests that the increased susceptibility to IA induced by these variants is likely related to their primary effects on the vascular tissue, and more particularly on the media layer of the wall of cerebral arteries

Acute surgical management of children with ruptured brain arteriovenous malformation

International audienceObjective: 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

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

International audienceOBJECTIVEUnderstanding 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.METHODSChildren 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.RESULTSA 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%]).CONCLUSIONSThe 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

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

International audienceOBJECTIVEUnderstanding 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.METHODSChildren 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.RESULTSA 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%]).CONCLUSIONSThe 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

Pediatric spinal pilocytic astrocytomas form a distinct epigenetic subclass from pilocytic astrocytomas of other locations and diffuse leptomeningeal glioneuronal tumours

Abstract Pediatric spinal low-grade glioma (LGG) and glioneuronal tumours are rare, accounting for less 2.8–5.2% of pediatric LGG. New tumour types frequently found in spinal location such as diffuse leptomeningeal glioneuronal tumours (DLGNT) have been added to the World Health Organization (WHO) classification of tumours of the central nervous system since 2016, but their distinction from others gliomas and particularly from pilocytic astrocytoma (PA) are poorly defined. Most large studies on this subject were published before the era of the molecular diagnosis and did not address the differential diagnosis between PAs and DLGNTs in this peculiar location. Our study retrospectively examined a cohort of 28 children with LGGs and glioneuronal intramedullary tumours using detailed radiological, clinico-pathological and molecular analysis. 25% of spinal PAs were reclassified as DLGNTs. PA and DLGNT are nearly indistinguishable in histopathology or neuroradiology. 83% of spinal DLGNTs presented first without leptomeningeal contrast enhancement. Unsupervised t-distributed stochastic neighbor embedding (t-SNE) analysis of DNA methylation profiles showed that spinal PAs formed a unique methylation cluster distinct from reference midline and posterior fossa PAs, whereas spinal DLGNTs clustered with reference DLGNT cohort. FGFR1 alterations were found in 36% of spinal tumours and were restricted to PAs. Spinal PAs affected significantly younger patients (median age 2 years old) than DLGNTs (median age 8.2 years old). Progression-free survival was similar among the two groups. In this location, histopathology and radiology are of limited interest, but molecular data (methyloma, 1p and FGFR1 status) represent important tools differentiating these two mitogen-activated protein kinase (MAPK) altered tumour types, PA and DLGNT. Thus, these molecular alterations should systematically be explored in this type of tumour in a spinal location