Pediatric temporal low-grade glial tumors: epilepsy outcome following resection in 48 children

Purpose

This paper summarizes our experience with surgical treatment of pediatric low-grade glial temporal lobe tumors focusing on the long-term outcome of seizures and identifying factors associated with seizure control and failure.

Methods

We reviewed all medical records of pediatric patients that underwent temporal lobe surgery due to seizures at our institution between 1997 and 2009. Only patients with temporal lobe tumors were included in this series. The files were retrospectively reviewed for seizure history. All children had undergone pre- and postoperative evaluation, neurological examination, EEG, and MRI.

Results

The cohort includes 48 children with mean follow-up time of 5.15?years (1?C12?years). The mean age at surgery was 8.2?years (1?C18.1) and the mean seizure duration until surgery was 2.6?years. All lesions in the cohort were low-grade tumors; pilocytic astrocytoma was the most common (41%). Eighty-three percent of the patients were classified as Engel class I following surgery. There was no correlation between Engel score and the preoperative epilepsy duration, age of seizure onset or type of seizures, and pathology. The surgical complication rate was 4.1% (2/48).

Conclusions

Surgical treatment for seizure control in children and adolescents with low-grade temporal tumors provides excellent long-term results.     

PET and SPECT studies in children with hemispheric low-grade gliomas

Molecular imaging is playing an increasing role in the pretreatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting, and improved detection of tumor recurrence. This review provides a brief overview of single-photon emission computed tomography (SPECT) studies followed by a more detailed review of the clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity, and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pretreatment and post-treatment evaluation of pediatric brain tumors.     

Cerebral tumors in children presenting with epilepsy.

The records of 20 children with seizures who had cerebral tumor confirmed histologically between 1979 and 1989 have been reviewed. These patients represented 2.9% of all children presenting with seizures. Forty percent were aged 15 months or younger, all of whom presented with partial seizures. Initial misdiagnosis of seizures occurred in 25% of these infants. Examination was normal in 75% of the study group. Behavior disturbance was present in 50%, with deterioration occurring in 60% of these. Electroencephalograms revealed focal abnormalities in 62% and generalized abnormalities in 25% when performed. Cranial ultrasound was performed in two cases, with false-negative results. Computed tomographic scan findings were not diagnostic of tumor in 40%. Magnetic resonance imaging confirmed the presence of tumor in all children in whom it was performed. Tumors most frequently involved the temporal lobes (55%) and the frontal lobes (40%). Surgical intervention resulted in considerable improvement in seizure control in 75%. Surgery is useful in the control of tumor-related seizures and should be considered early in the treatment of this disorder. Suspicion of tumor should increase when seizures are partial or refractory, particularly if intelligence and physical examination are normal or if there is progressive deterioration in behavior. The most appropriate type of brain imaging is magnetic resonance imaging scan.     

儿童鞍区肿瘤的视觉传导通路DTI特征分析

目的 应用磁共振弥散张量成像（DTI）和弥散张量纤维束成像（DTT）评估儿童鞍区肿瘤的视神经受损情况。方法 对24例儿童鞍区肿瘤（其中视交叉胶质瘤12例、鞍区颅咽管瘤7例、三脑室畸胎瘤2例、下丘脑错构瘤2例、斜坡脊索瘤1例）病例进行DTI和DTT检查,计算双侧视神经的部分各向异性（FA）值,并进行统计学分析。结果 根据显示的视交叉位置形态以及与肿瘤的空间结构关系,24例患儿可分为视交叉破坏组（12例）和视交叉压迫组（12例）。破坏组双侧视神经FA值均明显低于压迫组（P<0.05）。结论 DTI和DTT检查可以清晰的显示儿童鞍区肿瘤与视路神经纤维束的空间关系,其获得的参数FA值可以用来评价视路损伤的性质和程度。     

Cerebral cortical dysplasia: assessment by MRI and SPECT

The objective of this study was to establish correlations between image findings and pathologic deficits in patients with cerebral cortical malformations. The results of magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) in addition to clinical data for 15 patients with cerebral cortical malformations were reviewed retrospectively. MRI led to the diagnoses of bilateral perisylvian syndrome, hemimegalencephaly, focal polymicrogyria, band-heterotopia, and focal cortical dysplasia (FCD). Interictal SPECT did not reveal hypoperfusion in any case of polymicrogyria. Ictal SPECT images revealed hyperperfusion of the lesion in three patients with polymicrogyria, with accompanying hyperperfusion of the basal ganglia in two of the three patients. On the other hand, interictal SPECT images demonstrated hypoperfusion of the lesion in four patients with FCD. Ictal SPECT images revealed hypoperfusion of the lesion in two patients, hyperperfusion of the lesion in one patient, and hypoperfusion of the basal ganglia in two patients with FCD. This difference in perfusion between polymicrogyria and FCD observed in this study may reflect histologically different characteristics. This relative hyperperfusion of the cortex and the basal ganglia observed on ictal SPECT, which was found in two polymicrogyria patients with complex partial seizures and partial seizures evolving to secondary generalized seizures, respectively, suggests that the cortical-subcortical interaction is related to the mechanism of loss of consciousness or seizure generation.     

CT and MRI aspects of supratentorial hemispheric tumors of childhood and adolescence

The neuroradiological features of supratentorial hemispheric tumors (SHTs) were studied in 27 patients whose ages ranged from 11 months to 18 years. Astrocytomas constitued 10 of the 27 SHTs. On computed tomography low-grade astrocytomas were in most cases hypodense; after intravenous administration of contrast medium, pilocytic astrocytomas enhanced, whereas fibrillary astrocytomas did not. Gd-DPTA-enhanced magnetic resonance imaging was the most useful technique for the assessment of recurrences. Atypical imaging features were observed in one glioblastoma and in oligodendrogliomas (in half of the cases no calcifications were found). Gangliogliomas were surprisingly rather frequent in our series (5/27) and appeared in three cases as low-density, well-circumscribed lesions, not calcified and without edema and mass effect, while in two cases they had pronounced perifocal edema without clear demarcation. A rare desmoplastic infantile ganglioglioma was observed. The two meningiomas showed malignant behavior.     

Rightward hemispheric asymmetries in auditory language cortex in children with autistic disorder: an MRI investigation

Purpose: determine if language disorder in children with autistic disorder (AD) corresponds to abnormalities in hemispheric asymmetries in auditory language cortex. Methods: MRI morphometric study in children with AD (n = 50) to assess hemispheric asymmetries in auditory language cortex. A key region of interest was the planum temporale (PT), which is larger in the left hemisphere in most healthy individuals. Results: (i) Heschl’s gyrus and planum polare showed typical hemisphere asymmetry patterns; (ii) posterior Superior Temporal Gyrus (pSTG) showed significant rightward asymmetry; and (iii) PT showed a trend for rightward asymmetry that was significant when constrained to right-handed boys (n = 30). For right-handed boys, symmetry indices for pSTG were significantly positively correlated with those for PT. PT asymmetry was age dependent, with greater rightward asymmetry with age. Conclusions: results provide evidence for rightward asymmetry in auditory association areas (pSTG and PT) known to subserve language processing. Cumulatively, our data provide evidence for a differing maturational path for PT for lower functioning children with AD, with both pre- and post-natal experience likely playing a role in PT asymmetry.

Electronic supplementary material

The online version of this article (doi:10.1007/s11689-009-9010-2) contains supplementary material, which is available to authorized users.     

The nonspeech assessment of hemispheric specialization in retarded children

A visual half-field presentation technique was used to assess hemispheric asymmetries in young, language-deficient, retarded children who had been taught a nonspeech graphic symbol system. Unlike most tachistoscopic and dichotic listening methods, the present method did not require verbal instruction or verbal responses. In addition, the subjects' explicit understanding of the need to fixate visually prior to stimulus presentation was not necessary. Meaningful graphic symbols were recognized more accurately when presented to the hemisphere associated with the dominant eye and hand. Recognition of meaningless symbols was best when they were presented to the nondominant hemisphere. There was a significant hemispheric specialization effect similar to what would be expected in older, normal subjects using traditional methods.     

Outpatient assessment of neurovisual functions in children with Cerebral Palsy

This study examined the feasibility of the Atkinson Battery for Child Development for Examining Functional Vision (Atkinson, Anker, Rae, et al., 2002) to evaluate neurovisual functions of children with neurodevelopmental disorders in outpatient setting. A total of 90 patients underwent a comprehensive evaluation. Among these, a group of 33 children with Cerebral Palsy (CP), mean age 6 years, with different types of CP (26% diplegic, 37% hemiplegic and 37% tetraplegic) were selected to constitute the cohort of the study. Visual sensory measures as well as higher level visual functions were considered. Overall, 73% patients had impairments at the assessment protocol, the majority of which presenting difficulties on both visuoperceptual and visuospatial tasks (79%). Subgroups of participants presented similar profiles of impairments with spared basic visuocognitive abilities and limitations in visuoperceptual and visuospatial domains. The Atkinson's battery proved to be valuable for evaluation in outpatient setting and follow-up testing. Some limitations emerged. For the definition of personalized and detailed rehabilitation programs a breakdown of the different components of vision and subsequent in-depth evaluation are needed.     

3.0T磁共振对脑肿瘤运动区脑功能及白质纤维束的术前评价

目的对脑肿瘤患者运动区脑功能进行术前评价及白质纤维束追踪,以指导临床手术。方法采用手指运动任务设计成像方法,在Siemens Verio 3.0T磁共振成像仪下对40例运动区脑肿瘤患者行数据采集。运用随机附带软件进行图像后处理分析,并对瘤体的实性成分、瘤周水肿区域的FA值、ADC值进行测量及统计分析。结果高、低级别胶质瘤的瘤体实性部分ADC、FA值及瘤周水肿的ADC均有统计学意义(实性部分ADC:1.19±0.14vs 1.38±0.13,t=1.59,P0.05;FA:0.26±0.03vs0.21±0.02,t=2.02,P0.05;瘤周水肿带ADC:1.36±0.20vs1.56±0.15,t=1.76,P0.05)。而瘤周水肿带FA值无统计学意义(0.03±0.02 vs 0.04±0.03,t=2.56,P0.05)。运动区fMRI显示,患侧对指运动显示半球初级运动皮质(M1)脑功能破坏、减弱、移位24例,辅助运动区(SMA)激活伴移位8例,肿瘤侧的次级运动脑区如运动前区(PMC)及顶上小叶(PSL)出现激活5例,3例脑功能无明显改变。DTI像表现为完全的各向同性扩散,方向编码彩色图(DEC)彩色方向图上不能证实纤维14例。FA明显降低,在彩色方向图上有异常的色彩8例,其余则表现为白质纤维束位置及方向异常,但FA正常或略微降低。以上表现可单独存在,但多数系同时并存。结论 ADC和FA可以对肿瘤的良恶性进行术前评估,fMRI、DEC和DTT可以立体形象地显示肿瘤对脑功能区及白质纤维束的影响,有助于活体、无创地从功能和结构两个方面显示脑肿瘤区的改变,实现最大程度地切除肿瘤和保护脑重要功能区。     

Neurosurgical tools to extend tumor resection in pediatric hemispheric low-grade gliomas: iMRI

Introduction

The treatment of low-grade gliomas (LGGs) in pediatric age is still controversial. However, most authors report longer life expectancy in case of completely removed cerebral gliomas. Intraoperative magnetic resonance imaging (iMRI) is increasingly utilized in the surgical management of intra-axial tumor in adults following the demonstration of its effectiveness. In this article, we analyze the management of LGG using iMRI focusing on its impact on resection rate and its limits in the pediatric population.

Methods

We performed review of the literature regarding the treatment of LGG using iMRI focusing on its impact on resection rate and its limits in the pediatric population. Some exemplary cases are also described.

Results

Intraoperative MRI allowed extension of tumor resection after the depiction of residual tumor at the intraoperative imaging control from 21 to 52 % of the cases in the published series. Moreover, the early reoperation rate was significantly lower when compared with the population treated without this tool (0 % vs 7–14 %). Some technical difficulties have been described in literature regarding the use of iMRI in the pediatric population especially for positioning due to the structure of the headrest coil designed for adult patients.

Conclusion

The analysis of the literature and our own experience with iMRI in children indicates significant advantages in the resection of LGG offered by the technique. All these advantages are obtained without elongation of the surgical times or increased risk for complications, namely infection. The main limit for a wider diffusion of iMRI for the pediatric neurosurgical center is the cost required, for acquisition of the system, especially for high-field magnet, and the environmental and organizational changes necessary for its use.

     

Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: thalamic lesions

Background

Tumors with epicenter in the thalamus occur in about 4 % of pediatric brain tumors. The histological diagnosis is mainly gliomas. Among them, low-grade glioma (LGG) constituted of a significant entity of the tumors (Cuccia et al., Childs Nerv Syst 13:514–521, 1997; Puget et al., J Neurosurg 106:354–362, 2007; Bernstein et al., J Neurosurg 61:649–656, 1984; Bilginer et al., Childs Nerv Syst 30:1493–1498, 2014). Since Kelly’s report in 1989, >90 % resection of thalamic tumors were achieved in reported series (Ozek and Ture, Childs Nerv Syst 18:450–6, 2002; Villarejo et al., Childs Nerv Syst 10:111–114, 1994; Moshel et al., Neurosurgery 61:66–75, 2007; Albright, J Neurosurg 100(5 Suppl Pediatrics): 468–472, 2004; Kelly, Neurosurgery 25:185–195, 1989; Drake et al., Neurosurgery 29: 27–33, 1991).

Materials and methods

Sixty-nine cases of thalamic tumors in children were retrospectively reviewed. There were 25 cases of LGGs. We analyzed our experience and correlated it with reported series.

Results

Summing up of 4 reported series and the present series, there were 267 cases of thalamic tumors in children. Among these tumors, 107 (40.1 %) were LGGs and 91 (34.1 %) were low-grade astrocytomas (LGAs). In the present series, all of the 25 LGGs were LGAs that consisted of 11 pilocytic astrocytomas (PAs) and 14 diffuse astrocytomas (DAs). Six cases received biopsy sampling only. The remaining 19 cases received different degrees of surgical resection via several approaches. Radical (>90 %) resection was achieved better in PAs comparing with DAs. There was no operative mortality. Two patients had increased neurological deficits. In a mean follow-up period of 11.9 years, three patients died of tumor progression and one patient died of anaplastic change. The 5- and 10-year overall survival (OS) was 87.1 and 87.1 %, respectively.

Conclusion

Thalamic LGGs are mainly LGAs and are indolent. The rate of >90 % resection was relatively low in the present series. By applying contemporary diagnostic MRI studies, surgical facilities, and appropriate approaches in selective cases, we may try maximum neuroprotective radical (>90 %) resection.

     

Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: insular lesions

Insula and paralimbic region represent a common location for gliomas in adulthood. However, limbic and paralimbic tumors are rare in children. Reports of pediatric insular tumors are scarce in literature, and most of them are included in adult’s series, so their management and outcome can be outlined only after extracting data from these reports. Due to their predominantly low grade, they usually have a benign course for some time, what make them ideal candidates for total resection. However, their intricate location and spread to key areas, including the temporal lobe, make them a surgical challenge. The transsylvian route, with or without resection of the frontal and/or temporal operculae, which requires exposure of part or all of the insula is commonly selected for insular tumor approaches. Intraoperative functional mapping is a standard procedure for resection of central region tumors in adults. In children and young individuals, awake craniotomy is not always possible and surgical planning usually relay on functional and anatomical preoperative studies. The main goal when approaching an insular tumor is to achieve the largest extent of resection to increase overall patient survival while preserving the functional status, minimizing postoperative morbidity and increasing the quality of life. The extent of resection seems to be correlated also with the control of associated (and usually intractable) epilepsy.     

An integrative molecular and genomic analysis of pediatric hemispheric low-grade gliomas: an update

Hemispheric low-grade gliomas account for the second most common location in pediatric low-grade gliomas (PLGGs) after the cerebellum. The pathological spectrum includes gangliogliomas, dysembryoplastic neuroepithelial tumors (DNETs), diffuse astrocytomas, pilocytic astrocytomas, and pleomorphic xanthoastrocytomas (PXAs), among others. Clinically, hemispheric PLGGs represent a well-recognized cause of intractable epilepsy in children and adolescents. With an excellent long-term outcome, surgery remains the cornerstone and patients with gross total resection typically do not need any further therapies. The recent literature about hemispheric PLGGs was reviewed to provide an up-to-date overview of the molecular and cell biology of these tumors. Hemispheric PLGGs can harbor multiple alterations involving BRAFV600E, FGFR, NTRK, MYB/MYBL1, IDH, and BRAF-KIAA1549 fusions. However, the clinical significance of most of these alterations is still to be defined. The role of RAS/MAPK mutations and other alterations in hemispheric PLGGs is of interest from diagnostic, prognostic, and therapeutic perspectives. Molecular testing for these tumors should be encouraged, since the findings can have an important impact not only in prognosis but also in therapeutic strategies.     

Cerebral activation in children and adolescents with obsessive-compulsive disorder before and after treatment: a functional MRI study

BACKGROUND: Structural and functional fronto-striatal abnormalities are involved in the pathophysiology of obsessive-compulsive disorder (OCD). The aims of the present study were: (a) to investigate possible regional brain dysfunction in premotor cortico-striatal activity in drug-na?ve children and adolescents with OCD; (b) to correlate brain activation with severity of obsessive-compulsive symptomatology; and (c) to detect possible changes in brain activity after pharmacological treatment. METHOD: Twelve children and adolescents (age range 7-18 years; seven male, five female) with DSM-IV obsessive-compulsive disorder and twelve healthy subjects matched for age, sex and intellectual level were studied. Functional magnetic resonance imaging data were obtained during the performance of simple and complex sequences. RESULTS: Comparing the complex motor condition with the simple control condition, both patients and controls showed a pattern of cerebral activation involving the fronto-parietal cortex and basal ganglia. Compared with controls, OCD patients presented significantly higher brain activation bilaterally in the middle frontal gyrus. After 6 months of pharmacological treatment and with clear clinical improvement, activation in the left insula and left putamen decreased significantly. CONCLUSION: In a paediatric OCD sample that was treatment na?ve and without another psychiatric disorder we showed hyperactivation of the circuits that mediate symptomatic expression of OCD. The cerebral activation decreases after treatment and clinical improvement.     

Regional and hemispheric determinants of language laterality: Implications for preoperative fMRI

Language is typically a function of the left hemisphere but the right hemisphere is also essential in some healthy individuals and patients. This inter‐subject variability necessitates the localization of language function, at the individual level, prior to neurosurgical intervention. Such assessments are typically made by comparing left and right hemisphere language function to determine “language lateralization” using clinical tests or fMRI. Here, we show that language function needs to be assessed at the region and hemisphere specific level, because laterality measures can be misleading. Using fMRI data from 82 healthy participants, we investigated the degree to which activation for a semantic word matching task was lateralized in 50 different brain regions and across the entire cortex. This revealed two novel findings. First, the degree to which language is lateralized across brain regions and between subjects was primarily driven by differences in right hemisphere activation rather than differences in left hemisphere activation. Second, we found that healthy subjects who have relatively high left lateralization in the angular gyrus also have relatively low left lateralization in the ventral precentral gyrus. These findings illustrate spatial heterogeneity in language lateralization that is lost when global laterality measures are considered. It is likely that the complex spatial variability we observed in healthy controls is more exaggerated in patients with brain damage. We therefore highlight the importance of investigating within hemisphere regional variations in fMRI activation, prior to neuro‐surgical intervention, to determine how each hemisphere and each region contributes to language processing. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Conventional chemotherapy and perspectives for molecular-based oncological treatment in pediatric hemispheric low-grade gliomas

Introduction

Pediatric low-grade gliomas (PLGG) are the most common primary central nervous system tumor in children. Patients in whom gross total resection can be achieved have an excellent overall (OS) and event-free survival (EFS) and do not require adjuvant therapy. However, children with unresectable tumors often experience multiple progressions and require additional treatment.

Conventional chemotherapy

Radiotherapy results in long-term tumor control, but it is associated with significant toxicity, making chemotherapy the preferred therapeutic option. Several chemotherapy combinations have been found to be successful in PLGG, but 5-year EFS has been below 60 % with most of them.

Molecular-based treatment

Recent molecular advances have led to a better understanding of the molecular pathways involved in the biology of LGG, allowing the development of promising tumor-specific, molecularly targeted therapies.

     

Neurosurgical tools to extend tumor resection in hemispheric low-grade gliomas: conventional and contrast enhanced ultrasonography

Purpose

Pediatric low-grade gliomas (LGGs) are the most frequent solid tumor in childhood. Based on an increasing number of literature reports, maximal safe resection is recommended as the first line of treatment whenever possible. However, distinguishing tumor tissue from the surrounding normal brain is often challenging with infiltrating neoplasms, even with the assistance of intraoperative, microscopic and conventional neuronavigation systems. Therefore, any technique that enhances the detection and visualization of LGGs intraoperatively is certainly desirable.

Methods

In this paper, we reviewed the role of intraoperative conventional ultrasound and contrast-enhanced ultrasound (CEUS) as a tool for extending tumor resection in LGGs. Moreover, our experience with this technology is reported and discussed.

Results

Both B-mode and CEUS are helpful in highlighting LGGs, detecting tumor margins and providing additional information such as vascularization, thus improving the safety of a more radical resection.

Conclusions

Although the full potentialities of the method are yet to be explored, intraoperative ultrasound is a promising tool in oncologic surgery and LGG surgery.