Pediatric Neurosurgery

Medulloblastoma classification

Medulloblastoma classification

In the 5th edition of the WHO classification, medulloblastomas, which are representative pediatric brain tumors, are categorized into four groups: WNT, SHH-TP53 wild, SHH-TP53 mutant, and non-WNT/non-SHH, based on their molecular background. While the histopathological findings still hold importance in predicting prognosis, the histopathological classification is no longer utilized in this edition. SHH medulloblastomas are further subdivided into two groups based on the presence or absence of TP53 mutation, as their clinical characteristics and prognosis differ. Group 3 and Group 4 medulloblastomas, recognized as distinct molecular groups in clinical practice, are combined into a single group called “non-WNT/non-SHH”, because they lack specific molecular pathway activation. Furthermore, based on methylation profiling, dividing SHH medulloblastoma into four subgroups and non-WNT/non-SHH medulloblastoma into eight subgroups was proposed. Understanding the unique clinical characteristics and prognosis associated with each group is crucial. However, it is important to acknowledge that our current understanding of prognosis is based on treatment approaches guided by clinical risk factors such as postoperative residual tumor volume and the presence of metastatic disease. This molecular-based classification holds promise in guiding the development of optimal treatment strategies for patients with medulloblastoma 1).

Nomenclature

The nomenclature and classification of medulloblastomas are rapidly evolving.

Medulloblastomas, molecularly defined

Medulloblastoma, WNT-activated

Medulloblastoma, SHH-activated and TP53-wildtype

Medulloblastoma, SHH-activated and TP53-mutant

Medulloblastoma non-WNT/non-SSH

In the World Health Organization Classification of Tumors of the Central Nervous System 2021, Group 3 medulloblastoma and group 4 medulloblastomas are grouped together under Medulloblastoma non-WNT/non-SSH, which is in turn divided into 8 subgroups.

Group 3 medulloblastoma

Group 3 medulloblastoma

Group 4 medulloblastoma

Group 4 medulloblastoma.

Misclassification between groups 3 and 4 is common. To address this issue, an AI-based R package called MBMethPred was developed based on DNA methylation and gene expression profiles of 763 medulloblastoma samples to classify subgroups using machine learning and neural network models. The developed prediction models achieved a classification accuracy of over 96% for subgroup classification by using 399 CpGs as prediction biomarkers. We also assessed the prognostic relevance of prediction biomarkers using survival analysis. Furthermore, we identified subgroup-specific drivers of medulloblastoma using functional enrichment analysis, Shapley values, and gene network analysis. In particular, the genes involved in the nervous system development process have the potential to separate medulloblastoma subgroups with 99% accuracy. Notably, our analysis identified 16 genes that were specifically significant for subgroup classification, including EP300, CXCR4, WNT4, ZIC4, MEIS1, SLC8A1, NFASC, ASCL2, KIF5C, SYNGAP1, SEMA4F, ROR1, DPYSL4, ARTN, RTN4RL1, and TLX2. Our findings contribute to enhanced survival outcomes for patients with medulloblastoma. Continued research and validation efforts are needed to further refine and expand the utility of our approach in other cancer types, advancing personalized medicine in pediatric oncology 2)

Standard-Risk Medulloblastoma

Tumor Resection Rate: Patients with standard-risk medulloblastoma typically have a high rate of tumor resection. This means that during surgery, the neurosurgeon was able to remove a significant portion of the tumor from the brain. Metastasis: Standard-risk patients usually do not have evidence of metastasis, which means that the cancer cells have not spread from the primary tumor site in the cerebellum to other parts of the central nervous system (CNS) or outside the CNS.

High-Risk Medulloblastoma

Tumor Resection Rate: Patients with high-risk medulloblastoma often have a lower rate of tumor resection. This indicates that during surgery, it may have been challenging to remove the tumor completely, and some cancerous tissue might remain.

Metastasis: High-risk patients typically have evidence of metastasis. This means that the cancer cells have spread from the primary tumor site in the cerebellum to other areas within the CNS or even outside the CNS, such as the spinal cord or other parts of the body. The classification into standard-risk and high-risk categories is essential for treatment planning and prognosis assessment. Patients with standard-risk medulloblastoma may have a more favorable prognosis because of the higher likelihood of complete tumor removal and the absence of metastasis. In contrast, high-risk patients may face a more challenging treatment course and potentially a poorer prognosis due to the presence of metastasis and the difficulty in achieving complete tumor resection.

It’s important to note that treatment approaches for these two risk groups may differ, with high-risk patients typically receiving more intensive therapies to address the increased complexity and aggressiveness of their disease. Additionally, advances in molecular and genetic profiling have led to further subclassifications within medulloblastoma, providing a more nuanced understanding of the disease and guiding personalized treatment decisions.

EpiGe-App

EpiGe

The diagnosis of medulloblastoma incorporates the histologic and molecular subclassification of clinical medulloblastoma samples into wingless (WNT)-activated, sonic hedgehog (SHH)-activated, group 3 and group 4 subgroups. Accurate medulloblastoma subclassification has important prognostic and treatment implications.

Harmony alignment reveals novel MB subgroup/subtype-associated subpopulations that recapitulate neurodevelopmental processes, including photoreceptor and glutamatergic neuron-like cells in molecular subgroups GP3 and GP4, and a specific nodule-associated neuronally-differentiated subpopulation in subgroup molecular SHH. Riemondy et al. definitively chart the spectrum of MB immune cell infiltrates, which include subpopulations that recapitulate developmentally-related neuron-pruning and antigen presenting myeloid cells. MB cellular diversity matching human samples is mirrored in subgroup-specific mouse models of MB 3)

Medulloblastoma, WNT-activated

Medulloblastoma, WNT-activated

Sonic hedgehog medulloblastoma

Sonic hedgehog medulloblastoma.

Medulloblastoma, SHH-activated

Medulloblastoma, SHH-activated

Medulloblastoma, non-WNT/non-SSH

Medulloblastoma non-WNT/non-SSH

Histology

Medulloblastoma histologically defined:

Classic medulloblastoma

Desmoplastic nodular medulloblastoma

Medulloblastoma with extensive nodularity

Medulloblastoma, large cell/anaplastic

Medulloblastoma, NOS.

Localization

see Cerebellar medulloblastomas

see Cerebellopontine angle medulloblastoma

see Multifocal medulloblastoma.

Subgrouping

Immunohistochemistry (IHC)-based and nanoString-based subgrouping methodologies have been independently described as options for medulloblastoma subgrouping, however, they have not previously been directly compared. D’Arcy described the experience with nanoString-based subgrouping in a clinical setting and compare this with our IHC-based results. Study materials included FFPE tissue from 160 medulloblastomas. Clinical data and tumor histology were reviewed. Immunohistochemical-based subgrouping using β-catenin, filamin A and p53 antibodies and nanoString-based gene expression profiling was performed. The sensitivity and specificity of IHC-based subgrouping of WNT and SHH-activated medulloblastomas was 91.5% and 99.54%, respectively. Filamin A immunopositivity highly correlated with SHH/WNT-activated subgroups (sensitivity 100%, specificity 92.7%, p < 0.001). Nuclear β-catenin immunopositivity had a sensitivity of 76.2% and specificity of 99.23% for the detection of WNT-activated tumors. Approximately 23.8% of WNT cases would have been missed using an IHC-based subgrouping method alone. nanoString could confidently predict medulloblastoma subgroup in 93% of cases and could distinguish group 3/4 subgroups in 96.3% of cases. nanoString-based subgrouping allows for a more prognostically useful classification of clinical medulloblastoma samples 4).

Molecular subgrouping was performed by immunohistochemistry (IHC) for beta catenin, GAB1 and YAP1; FISH for MYC amplification, and sequencing for CTNNB1, and by NanoString Assay on the same set of MBs. A subset of cases was subjected to 850k DNA methylation array.

IHC + FISH classified MBs into 15.8% WNT, 16.8% SHH, and 67.4% non-WNT/non-SHH subgroups; with MYC amplification identified in 20.3% cases of non-WNT/non-SHH. NanoString successfully classified 91.6% MBs into 25.3% WNT, 17.2% SHH, 23% Group 3 and 34.5% Group 4. However, NanoString assay failure was seen in eight cases, all of which were > 8-years-old formalin-fixed paraffin-embedded tissue blocks. Concordant subgroup assignment was noted in 88.5% cases, while subgroup switching was seen in 11.5% cases. Both methods showed prognostic correlation. Methylation profiling performed on discordant cases revealed 1 out of 4 extra WNT identified by NanoString to be WNT, others aligned with IHC subgroups; extra SHH by NanoString turned out to be SHH by methylation.

Both IHC supplemented by FISH and NanoString are robust methods for molecular subgrouping, albeit with few disadvantages. IHC cannot differentiate between Groups 3 and 4, while NanoString cannot classify older-archived tumors, and is not available at most centres. Thus, both the methods complement each other and can be used in concert for high confidence allotment of molecular subgroups in clinical practice 5).

The maturation of medulloblastoma into a ganglion cell-rich lesion is very rare, with few well-characterized previous reports. Given the rare nature of this entity, it would be of great value to understand the process of posttreatment maturation and the genetic and treatment factors which contribute to this phenomenon 6).

Pediatric Medulloblastoma

Pediatric Medulloblastoma.

Test and Answers

In the 5th edition of the WHO classification, how are medulloblastomas categorized based on their molecular background? a) Low-risk and high-risk b) Classic and desmoplastic nodular c) WNT, SHH-TP53 wild, SHH-TP53 mutant, and non-WNT/non-SHH d) Standard-risk and high-risk

Which subgroup of medulloblastoma is characterized by activation of the WNT pathway? a) Group 3 b) SHH-activated c) WNT-activated d) Non-WNT/non-SHH

What is the significance of TP53 mutation in SHH medulloblastomas? a) It indicates a better prognosis b) It indicates a worse prognosis c) It has no impact on prognosis d) It classifies the tumor as a WNT-activated subtype

How many subgroups are non-WNT/non-SHH medulloblastomas divided into based on methylation profiling in the 5th edition of the WHO classification? a) 2 b) 4 c) 6 d) 8

What are the clinical risk factors often used for prognosis assessment in medulloblastoma? a) Molecular subgroups b) Histopathological findings c) Age and gender d) Tumor location and size

Which of the following statements is true regarding the classification of medulloblastoma? a) Histopathological classification is the primary method used in the 5th edition of the WHO classification. b) Molecular subgroups are not considered relevant for treatment planning. c) Molecular subgroups guide the development of optimal treatment strategies. d) All medulloblastomas are classified into two main subgroups: WNT and SHH-activated.

What is the main difference between standard-risk and high-risk medulloblastoma? a) The presence of TP53 mutation b) The rate of tumor resection c) The age of the patient d) The presence of metastasis

Which of the following is NOT a method used for molecular subgrouping of medulloblastoma? a) Immunohistochemistry (IHC) b) NanoString Assay c) FISH for MYC amplification d) DNA methylation analysis

What is the advantage of using NanoString Assay for molecular subgrouping of medulloblastoma? a) It can classify older-archived tumor samples. b) It has a higher success rate in classifying tumors. c) It is based on DNA methylation profiling. d) It cannot be used in clinical practice.

Which subgroup of medulloblastoma is characterized by MYC amplification in some cases? a) WNT-activated b) SHH-activated c) Group 3 d) Group 4

Answers:

c) WNT, SHH-TP53 wild, SHH-TP53 mutant, and non-WNT/non-SHH c) WNT-activated b) It indicates a worse prognosis d) 8 c) Age and gender c) Molecular subgroups guide the development of optimal treatment strategies. b) The rate of tumor resection d) DNA methylation analysis a) It can classify older-archived tumor samples. c) Group 3

References

1)

Yamaguchi S, Fujimura M. [Medulloblastoma]. No Shinkei Geka. 2023 Sep;51(5):858-866. Japanese. doi: 10.11477/mf.1436204827. PMID: 37743337.
2)

Sharif Rahmani E, Lawarde A, Lingasamy P, Moreno SV, Salumets A, Modhukur V. MBMethPred: a computational framework for the accurate classification of childhood medulloblastoma subgroups using data integration and AI-based approaches. Front Genet. 2023 Sep 7;14:1233657. doi: 10.3389/fgene.2023.1233657. PMID: 37745846; PMCID: PMC10513500.
3)

Riemondy KA, Venkataraman S, Willard N, Nellan A, Sanford B, Griesinger AM, Amani V, Mitra S, Hankinson TC, Handler MH, Sill M, Ocasio J, Weir SJ, Malawsky DS, Gershon TR, Garancher A, Wechsler-Reya RJ, Hesselberth JR, Foreman NK, Donson AM, Vibhakar R. Neoplastic and immune single cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma. Neuro Oncol. 2021 Jun 2:noab135. doi: 10.1093/neuonc/noab135. Epub ahead of print. PMID: 34077540.
4)

D’Arcy CE, Nobre LF, Arnaldo A, Ramaswamy V, Taylor MD, Naz-Hazrati L, Hawkins CE. Immunohistochemical and nanoString-Based Subgrouping of Clinical Medulloblastoma Samples. J Neuropathol Exp Neurol. 2020 Jan 30. pii: nlaa005. doi: 10.1093/jnen/nlaa005. [Epub ahead of print] PubMed PMID: 32053195.
5)

Kaur K, Jha P, Pathak P, Suri V, Sharma MC, Garg A, Suri A, Sarkar C. Approach to molecular subgrouping of medulloblastomas: Comparison of NanoString nCounter assay versus combination of immunohistochemistry and fluorescence in-situ hybridization in resource constrained centres. J Neurooncol. 2019 May 18. doi: 10.1007/s11060-019-03187-y. [Epub ahead of print] PubMed PMID: 31104222.
6)

Mullarkey MP, Nehme G, Mohiuddin S, et al. Posttreatment Maturation of Medulloblastoma into Gangliocytoma: Report of 2 Cases [published online ahead of print, 2020 Sep 3]. Pediatr Neurosurg. 2020;1-10. doi:10.1159/000509520

Test your knowledge about Foramen magnum stenosis in Achondroplasia

What is the significance of foramen magnum stenosis in achondroplasia?

a) It is a cosmetic issue with no medical consequences.

b) It can lead to compression of the brainstem and spinal cord, resulting in severe health problems.

c) It only affects adults with achondroplasia.

d) It is completely unrelated to achondroplasia.

What contributes to the narrowing of the foramen magnum in infants with achondroplasia?

a) Growth spurt during adolescence

b) Restricted growth in the first 2 years of life and premature closure of skull plate synchondroses

c) Diet and nutrition

d) Lack of physical activity

How can foramen magnum stenosis be diagnosed?

a) By physical examination alone

b) Through a blood test

c) By acquiring effective neuroimaging

d) By measuring head circumference

Why is standardized imaging protocol essential for children with achondroplasia?

a) It helps in diagnosing achondroplasia itself.

b) It ensures that clinically useful neuroimaging is performed and reduces unnecessary radiation exposure.

c) It is required for insurance purposes.

d) It helps in determining the child's future height.

How did the European Achondroplasia Forum (EAF) contribute to the management of foramen magnum stenosis?

a) By recommending surgery for all cases

b) By providing guidelines for the detection and management of foramen magnum stenosis

c) By developing a new drug

d) By organizing awareness campaigns

What is the Achondroplasia Foramen Magnum Score (AFMS) used for?

a) To assess the severity of sleep apnea in achondroplasia patients

b) To diagnose achondroplasia in infants

c) To evaluate the severity of foramen magnum stenosis in infants with achondroplasia

d) To measure head circumference

What does a high Total Apnea and Hypopnea Index (TAHI) indicate in relation to foramen magnum stenosis?

a) It suggests that the patient has no stenosis.

b) It indicates severe foramen magnum stenosis.

c) It has no correlation with foramen magnum stenosis.

d) It indicates a need for dietary changes.

What is the sensitivity of clinical examination and CRS (cardiorespiratory sleep studies) for predicting the effects of foramen magnum stenosis on the spinal cord?

a) High sensitivity

b) Low sensitivity

c) No sensitivity

d) Moderate sensitivity

How can routine screening with MRI using AFMS benefit infants with achondroplasia?

a) It helps in cosmetic improvements.

b) It has no benefits.

c) It aids in detecting early spinal cord changes and can reduce infant morbidity and mortality.

d) It is only useful for diagnosing other medical conditions.

What percentage of infants required neurosurgery in the study mentioned in the text?

a) 0%

b) 10%

c) 25%

d) 50%

Answers:

b) It can lead to compression of the brainstem and spinal cord, resulting in severe health problems.
b) Restricted growth in the first 2 years and premature closure of skull plate synchondroses
c) By acquiring effective neuroimaging
b) It ensures that clinically useful neuroimaging is performed and reduces unnecessary radiation exposure.
b) By providing guidelines for the detection and management of foramen magnum stenosis
c) To evaluate the severity of foramen magnum stenosis in infants with achondroplasia
b) It indicates severe foramen magnum stenosis.
b) Low sensitivity
c) It aids in detecting early spinal cord changes and can reduce infant morbidity and mortality.
c) 25%

Craniopharyngioma endoscopic endonasal approach

Craniopharyngioma endoscopic endonasal approach

Latest Craniopharyngioma endoscopic endonasal approach PubMed-related Articles

Indications

Craniopharyngioma endoscopic endonasal approach Indications.

Systematic reviews

The endoscopic endonasal approach (EEA) for craniopharyngiomas has proven to be a safe option for extensive tumor resection, with minimal or no manipulation of the optic nerves and excellent visualization of the superior hypophyseal artery branches when compared to the Transcranial Approach (TCA). However, there is an ongoing debate regarding the criteria for selecting different approaches. To explore the current results of EEA and discuss its role in the management of craniopharyngiomas, Figueredo et al. performed MEDLINE, Embase, and LILACS searches from 2012 to 2022. Baseline characteristics, the extent of resection, and clinical outcomes were evaluated. Statistical analysis was performed through an X2 and Fisher exact test, and a comparison between quantitative variables through a Kruskal-Wallis and verified with post hoc Bonferroni. The tumor volume was similar in both groups (EEA 11.92 cm3, -TCA 13.23 cm3). The mean follow-up in months was 39.9 for EEA and 43.94 for TCA, p = 0.76). The EEA group presented a higher visual improvement rate (41.96% vs. 25% for TCA, p < 0.0001, OR 7.7). Permanent DI was less frequent with EEA (29.20% vs. 67.40% for TCA, p < 0.0001, OR 0.2). CSF Leaks occurred more frequently with EEA (9.94% vs. 0.70% for TCA, p < 0.0001, OR 15.8). Recurrence rates were lower in the EEA group (EEA 15.50% vs. for TCA 21.20%, p = 0.04, OR 0.7). The results demonstrate that, in selected cases, EEA for resection of craniopharyngiomas is associated with better results regarding visual preservation and extent of tumor resection. Postoperative cerebrospinal fluid fistula rates associated with EEA have improved compared to the historical series. The decision-making process should consider each person’s characteristics; however, it is noticeable that recent data regarding EEA justify its widespread application as a first-line approach in centers of excellence for skull base surgery 1).

Qiao et al., conducted a systematic review and meta-analysis. They conducted a comprehensive search of PubMed to identify relevant studies. Pituitary, hypothalamus functions and recurrence were used as outcome measures. A total of 39 cohort studies involving 3079 adult patients were included in the comparison. Among these studies, 752 patients across 17 studies underwent endoscopic transsphenoidal resection, and 2327 patients across 23 studies underwent transcranial resection. More patients in the endoscopic group (75.7%) had visual symptoms and endocrine symptoms (60.2%) than did patients in the transcranial group (67.0%, p = 0.038 and 42.0%, p = 0.016). There was no significant difference in hypopituitarism and pan-hypopituitarism after surgery between the two groups: 72.2% and 43.7% of the patients in endoscopic group compared to 80.7% and 48.3% in the transcranial group (p = 0.140 and p = 0.713). We observed same proportions of transient and permanent diabetes insipidus in both groups. Similar recurrence was observed in both groups (p = 0.131). Pooled analysis showed that neither weight gain (p = 0.406) nor memory impairment (p = 0.995) differed between the two groups. Meta-regression analysis revealed that gross total resection contributed to the heterogeneity of recurrence proportion (p < 0.001). They observed similar proportions of endocrine outcomes and recurrence in both endoscopic and transcranial groups. More recurrences were observed in studies with lower proportions of gross total resection 2).

Komotar et al performed a systematic review of the available published reports after endoscope-assisted endonasal approaches and compared their results with transsphenoidal purely microscope-based or transcranial microscope-based techniques.

The endoscopic endonasal approach is a safe and effective alternative for the treatment of certain craniopharyngiomas. Larger lesions with more lateral extension may be more suitable for an open approach, and further follow-up is needed to assess the long-term efficacy of this minimal access approach 3)

Nowadays, an endoscopic endonasal approach (EEA) provides an “easier” way for CPs resection allowing a direct route to the tumor with direct visualization of the surrounding structures, diminishing inadvertent injuries, and providing a better outcome for the patient 4).

Historically, aggressive surgical resection was the treatment goal to minimize the risk of tumor recurrence via open transcranial midline, anterolateral, and lateral approaches, but could lead to clinical sequela of visual, endocrine, and hypothalamic dysfunction. However, recent advances in the endoscopic endonasal approach over the last decade have mostly supplanted transcranial surgery as the optimal surgical approach for these tumors. With viable options for adjuvant radiation therapy, targeted medical treatment, and alternative minimally invasive surgical approaches, the management paradigm for craniopharyngiomas has shifted from aggressive open resection to more minimally invasive but maximally safe resection, emphasizing quality of life issues, particularly in regards to visual, endocrine, and hypothalamic function. 5).

Craniopharyngioma surgery has evolved over the last two decades. Traditional transcranial microsurgical approaches were the only option until the advent of the endoscopic endonasal approach 6).

The endoscopic endonasal approach for craniopharyngiomas is increasingly used as an alternative to microsurgical transsphenoidal or transcranial approaches. It is a step forward in treatment, providing improved resection rates and better visual outcome. Especially in retrochiasmatic tumors, this approach provides better lesion access and reduces the degree of manipulations of the optic apparatus. The panoramic view offered by endoscopy and the use of angulated optics allows the removal of lesions extending far into the third ventricle avoiding microsurgical brain splitting. Intensive training is required to perform this surgery 7).

The highest priority of current surgical craniopharyngioma treatment is to maximize tumor removal without compromising the patients’ long-term functional outcome. Surgical damage to the hypothalamus may be avoided or at least ameliorated with a precise knowledge regarding the type of adherence for each case.

Endoscopic endonasal approach, has been shown to achieve higher rates of hypothalamic preservation regardless of the degree of involvement by tumor 8) 9).

Extended endoscopic transsphenoidal approach have gained interest. Surgeons have advocated for both approaches, and at present there is no consensus whether one approach is superior to the other.

With the widespread use of endoscopes in endonasal surgery, the endoscopic transtuberculum transplanum approach have been proposed as an alternative surgical route for removal of different types of suprasellar tumors, including solid craniopharyngiomas in patients with normal pituitary function and small sella.

As part of a minimally disruptive treatment paradigm, the extended endoscopic transsphenoidal approach has the potential to improve rates of resection, improve postoperative visual recovery, and minimize surgical morbidity 10).

Corridors

The endoscopic endonasal approach has become a valid surgical technique for the management of craniopharyngiomas. It provides an excellent corridor to infra- and supradiaphragmatic midline craniopharyngiomas, including the management of lesions extending into the third ventricle chamber. Even though indications for this approach are rigorously lesion based, the data confirm its effectiveness in a large patient series 11).

The endoscopic endonasal approach offers advantages in the management of craniopharyngiomas that historically have been approached via the transsphenoidal approach (i.e., purely intrasellar or intra-suprasellar infradiaphragmatic, preferably cystic lesions in patients with panhypopituitarism).

Use of the extended endoscopic endonasal approach overcomes the limits of the transsphenoidal route to the sella enabling the management of different purely suprasellar and retrosellar cystic/solid craniopharyngiomas, regardless of the sellar size or pituitary function 12).

They provide acceptable results comparable to those for traditional craniotomies. Endoscopic endonasal surgery is not limited to adults and actually shows higher resection rates in the pediatric population 13).

Infrachiasmatic corridor

Infrachiasmatic corridor

Complications

Craniopharyngioma endoscopic endonasal approach complications.

Case series

see Craniopharyngioma endoscopic endonasal approach case series.

References

1)

Figueredo LF, Martínez AL, Suarez-Meade P, Marenco-Hillembrand L, Salazar AF, Pabon D, Guzmán J, Murguiondo-Perez R, Hallak H, Godo A, Sandoval-Garcia C, Ordoñez-Rubiano EG, Donaldson A, Chaichana KL, Peris-Celda M, Bendok BR, Samson SL, Quinones-Hinojosa A, Almeida JP. Current Role of Endoscopic Endonasal Approach for Craniopharyngiomas: A 10-Year Systematic Review and Meta-Analysis Comparison with the Open Transcranial Approach. Brain Sci. 2023 May 23;13(6):842. doi: 10.3390/brainsci13060842. PMID: 37371322.
2)

Qiao N. Endocrine outcomes of endoscopic versus transcranial resection of craniopharyngiomas: A system review and meta-analysis. Clin Neurol Neurosurg. 2018 Apr 7;169:107-115. doi: 10.1016/j.clineuro.2018.04.009. [Epub ahead of print] Review. PubMed PMID: 29655011.
3)

Komotar RJ, Starke RM, Raper DM, Anand VK, Schwartz TH. Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of craniopharyngiomas. World Neurosurg. 2012 Feb;77(2):329-41. doi: 10.1016/j.wneu.2011.07.011. Epub 2011 Nov 1. Review. PubMed PMID: 22501020.
4)

Aragón-Arreola JF, Marian-Magaña R, Villalobos-Diaz R, López-Valencia G, Jimenez-Molina TM, Moncada-Habib JT, Sangrador-Deitos MV, Gómez-Amador JL. Endoscopic Endonasal Approach in Craniopharyngiomas: Representative Cases and Technical Nuances for the Young Neurosurgeon. Brain Sci. 2023 Apr 28;13(5):735. doi: 10.3390/brainsci13050735. PMID: 37239207; PMCID: PMC10216292.
5)

Hong CS, Omay SB. The Role of Surgical Approaches in the Multi-Modal Management of Adult Craniopharyngiomas. Curr Oncol. 2022 Feb 24;29(3):1408-1421. doi: 10.3390/curroncol29030118. PMID: 35323318; PMCID: PMC8947636.
6)

Fong RP, Babu CS, Schwartz TH. Endoscopic endonasal approach for craniopharyngiomas. J Neurosurg Sci. 2021 Apr;65(2):133-139. doi: 10.23736/S0390-5616.21.05097-9. PMID: 33890754.
7)

Baldauf J, Hosemann W, Schroeder HW. Endoscopic Endonasal Approach for Craniopharyngiomas. Neurosurg Clin N Am. 2015 Jul;26(3):363-75. doi: 10.1016/j.nec.2015.03.013. Epub 2015 May 26. PMID: 26141356.
8)

Tan TSE, Patel L, Gopal-Kothandapani JS, Ehtisham S, Ikazoboh EC, Hayward R, et al: The neuroendocrine sequelae of paediatric craniopharyngioma: a 40-year meta-data analysis of 185 cases from three UK centres. Eur J Endocrinol 176:359–369, 2017
9)

Yokoi H, Kodama S, Kogashiwa Y, Matsumoto Y, Ohkura Y, Nakagawa T, et al: An endoscopic endonasal approach for early-stage olfactory neuroblastoma: an evaluation of 2 cases with minireview of literature. Case Rep Otolaryngol 2015:541026, 2015
10)

Zacharia BE, Amine M, Anand V, Schwartz TH. Endoscopic Endonasal Management of Craniopharyngioma. Otolaryngol Clin North Am. 2016 Feb;49(1):201-12. doi: 10.1016/j.otc.2015.09.013. Review. PubMed PMID: 26614838.
11)

Cavallo LM, Frank G, Cappabianca P, Solari D, Mazzatenta D, Villa A, Zoli M, D’Enza AI, Esposito F, Pasquini E. The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients. J Neurosurg. 2014 May 2. [Epub ahead of print] PubMed PMID: 24785324.
12)

Cavallo LM, Solari D, Esposito F, Villa A, Minniti G, Cappabianca P. The Role of the Endoscopic Endonasal Route in the Management of Craniopharyngiomas. World Neurosurg. 2014 Dec;82(6S):S32-S40. doi: 10.1016/j.wneu.2014.07.023. Review. PubMed PMID: 25496633.
13)

Koutourousiou M, Gardner PA, Fernandez-Miranda JC, Tyler-Kabara EC, Wang EW, Snyderman CH. Endoscopic endonasal surgery for craniopharyngiomas: surgical outcome in 64 patients. J Neurosurg. 2013 Nov;119(5):1194-207. doi: 10.3171/2013.6.JNS122259. Epub 2013 Aug 2. PubMed PMID: 23909243.

Split cord malformation

Split cord malformation

General information

There is no uniformly accepted nomenclature for malformations characterized by duplicate or split spinal cords.

The term split cord malformation (SCM) was first introduced in 1992 by Pang et al., in an attempt to resolve the confusion existing in the pathological definition and the clinical significance of previously existing terminologies in the literature, diastematomyelia and diplomyelia, and the inconsistent usage of these two terms.

Pang et al have proposed the following. The term split cord malformation (SCM) should be used for all double spinal cords, all of which appear to have a common embryologic etiology 1).

The term split cord malformation (SCM) should be used for all double spinal cords, all of which appear to have a common embryologic etiology.

Split cord malformation (SCM) has a rich history and has intrigued physicians for over 200 years. Many well-known figures from the past such as Hans Chiari and Friedrich Daniel von Recklinghausen, both pathologists, made early postmortem descriptions of SCM. With the advent of MRI, these pathological embryological derailments can now often be detected and appreciated early and during life. Our understanding and ability to treat these congenital malformations as well as the terminology used to describe them have changed over the last several decades 2).

Classification

Split cord malformations (SCMs) are among the rare congenital spinal anomalies. In 1992, Pang et al, proposed the “Unified theory of embryogenesis” and explained the formation of SCM type 1 and 2. This theory has been widely accepted in the neurosurgical literature, backed by several studies. However, there have been reports in the literature that defy both, the classification as well as formation of SCMs, based on the unified theory of embryogenesis.

Pang et al. classified spinal cord duplication anomalies into types I and II. The first is characterized by two hemicords, each contained within its own dural sac, and separated by an osteocartillaginous septum. Type II is defined by two hemicords in the same dural sac, separated by a fibrous septum 3) 4).

Type I split cord malformation

Type 1.5 split cord malformation ? 5).

Type 2 split cord malformation.

Much confusion still exists concerning the pathological definitions and clinical significance of double spinal cord malformations. Traditional terms used to describe the two main forms of these rare malformations, diastematomyelia, and diplomyelia, add to the confusion by their inconsistent usage, ambiguities, and implications of their dissimilar embryogenesis. Based on the detailed radiographic and surgical findings of 39 cases of double cord malformations and the autopsy data on two other cases, this study endorses a new classification for double cord malformations and proposes a unified theory of embryogenesis for all their variant forms and features. The new classification recommends the term split cord malformation (SCM) for all double spinal cords. A Type I SCM consists of two hemicords, each contained within its own dural tube and separated by a dura-sheathed rigid osseocartilaginous median septum. A Type II SCM consists of two hemicords housed in a single dural tube separated by a nonrigid, fibrous median septum. These two essential features necessary for typing, the state of the dural tube and the nature of the median septum, do not ever overlap between the two main forms and can always be demonstrated by imaging studies so that accurate preoperative typing is always possible. All other associated structures in SCM such as paramedian nerve roots, myelomeningoceles manqué, and centromedian vascular structures frequently do overlap between types and are not reliable typing criteria. The unified theory of embryogenesis proposes that all variant types of SCMs have a common embryogenetic mechanism. Basic to this mechanism is the formation of adhesions between ecto- and endoderm, leading to an accessory neurenteric canal around which condenses an endomesenchymal tract that bisects the developing notochord and causes formation of two hemineural plates. The altered state of the emerging split neural tube and the subsequent ontogenetic fates of the constituent components of the endomesenchymal tract ultimately determine the configuration and orientation of the hemicords, the nature of the median septum, the coexistence of various vascular, lipomatous, neural, and fibrous oddities within the median cleft, the high association with open myelodysplastic and cutaneous lesions, and the seemingly unlikely relationship with fore and midgut anomalies. The multiple facets of this theory are presented in increasing complexity against the background of known embryological facts and theories; the validity of each facet is tested by comparing structures and phenomena predicted by the facet with actual radiographic, surgical, and histopathological findings of these 41 cases of SCM 6).

A new classification system proposed by Mahapatra and Gupta further divides type I SCM into four categories: Ia, bony spur in the center with equally duplicated cord above and below the spur; type Ib, bony spur at the superior pole with no space above and a large duplicated cord below; Ic, bony spur at the lower pole with a large duplicated cord above; and Id, bony spur straddling the bifurcation with no space above or below the spur 7).

Treatment

The risk of neurological deficits developing increases with age; hence, all patients with SCM should be surgically treated prophylactically even if they are asymptomatic 8).

see Type I Split Cord Malformation treatment.

Outcome

SCMs can lead to progressively worsening scoliosis and gait difficulties if left untreated.

Case series

From 1990 to 2014, 37 patients were operated. Five situations lead to the diagnosis (orthopedic disorders (n = 8), orthopedic and neurological disorders (n = 16), pure neurological disorders (n = 5), no symptoms except cutaneous signs (n = 7), antenatal diagnosis (n = 1)). Scoliosis was the most common associated condition. The level of the spur was always under T7 except in one case. There were more type I (n = 22) than type II (n = 15) SCM.

Patients with preoperative neurological symptoms (n = 21) were improved in 71.4%. Five out of nine patients that had preoperative bladder dysfunction were improved. Eleven patients needed surgical correction of the scoliosis.

For us, the surgical procedure is mandatory even in case of asymptomatic discovery in order to avoid late clinical deterioration. In any case, the filum terminale need to be cut in order to untether completely the spinal cord. In case a surgical correction of a spinal deformity is needed, we recommend a two-stage surgery, for both SCM type. The SCM surgery can stop the evolution of scoliosis and it may just need an orthopedic treatment with a brace 9).

Over a 16-year period, Mahapatra encountered 300 cases of SCM at AIIMS. Over the same period, more than 1500 cases of NTD were managed. SCM was noticed in 20% of cases with NTD. Skin stigmata were noted in two-third of the cases, and scoliosis and foot deformity were observed in 50% and 48% cases, respectively. Motor and sensory deficits were observed in 80% and 70% cases, respectively. Commonest site affected was lumbar or dorsolumbar (55% and 23%, respectively). In 3% cases, it was cervical in location. Magnetic resonance imaging (MRI) scan revealed a large number of anomalies like lipoma, neuroenteric cyst, thick filum and dermoid or epidermoid cysts. All the patients were surgically treated. In type I, bony spurs were excised, and in type II, bands tethering the cord were released. Associated anomalies were managed in the same sitting. Patients were followed up from 3 months to 3 years.

Overall improvement was noticed in 50% and stabilization in 44% cases and deterioration of neurological status was recorded in 6% cases. However, 50% of those who deteriorated improved to preop status prior to discharge, 7-10 days following surgery.

SCM is rare and not many large series are available. They operated 300 cases and noticed a large number of associated anomalies and also multilevel and multisite splits. Improvement or stabilization was noted in 94% and deterioration in 6% cases. They recommended prophylactic surgery for our asymptomatic patients 10).

Mahapatra et al. in 2005 reported the first 254 cases of SCM treated surgically during a period of 16 years.

Patients’ demographic profiles, imaging studies, operative details, complications, and surgical outcomes were evaluated retrospectively. A new classification based on intraoperative findings is proposed. The mean age of the patients was 7.3 years (female/male 1.5:1). Type I SCM was seen in 156 patients (61.4%) and 98 patients (38.6%) had Type II SCM. Skin stigmata were present in 153 cases (60%); hypertrichosis, being the most common, was seen in 82 cases (32.3%). Asymmetrical lower-limb weakness and sphincter disturbances were present in 173 (68.1%) and 73 (33%) cases, respectively. Of the symptomatic cases, 39% (68 of 173) showed improvement in motor power, 57.9% (33 of 57) experienced sensory improvement, and 27.3% (20 of 73) regained continence. None of the 38 patients in the asymptomatic group had postoperative neurological deterioration. The neurological status was unchanged in 63% of the cases. A new subclassification of Type I SCM is proposed, based on the intraoperative location of a bone spur causing the split, which may have a bearing on surgical dissection and outcome. Based on the authors’ experience with 25 cases of Type I SCM, they have classified the disorder into four subtypes: Type Ia, bone spur located in the center with duplicated cord above and below the spur (12 cases); Type Ib, bone spur at the superior pole with no space above it (four cases); Type Ic, bone spur at the lower pole with large duplicated cord above (three cases); and Type Id, bone spur straddling the bifurcation with no space above or below the spur (six cases). The risk of injury to the hemicords is highest in the Id subtype (four of six patients in this group deteriorated neurologically in the present series, whereas none with subtypes Ia-c worsened).

This is the largest series on SCMs so far reported in the world literature The risk of neurological deficits developing increases with age; hence, all patients with SCM should be surgically treated prophylactically even if they are asymptomatic. This new classification is easy to use and remember and takes into account the use of intraoperative findings that may have a bearing on surgical outcome 11).

Retrospective analysis of 19 cases of SCM, thirteen were grouped under (Pang) type I and 6 in type II. Their ages ranged from 1 month to 9 years (mean 3.5 years). 14 of these were male children. The NOS without neurological signs was detected in 6 cases whereas pure neurological signs without NOS were seen in 8 patients. However, the rest 5 had a mixed picture of NOS and neurological dysfunction. Nine of 19 cases presented with cutaneous stigmata, mainly in the form of a hairy patch. 18 cases had other associated craniospinal anomalies i.e. hydrocephalus, meningomyelocele, syrinx, dermoid, teratoma, etc. Detethering of the cord was done in all cases by the removal of fibrous/bony septum. Associated anomalies were also treated accordingly. Follow up of these cases ranged from 6 months to 6 years. Six cases of NOS group neither showed deterioration nor improvement, and remained static on follow up. However, four of 8 children with neurological signs showed improvement in their motor weakness, and 1 in saddle hypoaesthesia as well as bladder/bowel function. In 5 cases of a mixed group, two had improvement in their weakness and one in hypoaesthesia, but no change was noticed in NOS of this group as well. Hence surgery seemed to be effective, particularly in patients with neurological dysfunction 12).

Proctor and Scott reviewed the results obtained in 16 patients in whom the senior author performed surgery over a 13-year period (average length of follow up almost 8 years).

Presentation, surgical approach, and the outcome are evaluated, and the long-term outcome of neurological status, pain, bowel/bladder disturbance, and spinal deformities are emphasized.

The primary conclusion is that patients with SCM generally tolerate surgery well and experience few complications. Neurological deterioration is rare except in cases in which retethering occurs, (two patients in this series). Although impaired bowel and bladder function was stabilized or improved and pain was reliably relieved postoperatively, preexisting vertebral column deformities usually progressed after surgery and, in most cases, required spinal fusion 13).

In 2000 Forty-eight patients of split cord malformation operated during a six years period were studied clinically and radiologically.

The mean age of symptomatic patients was more than that of asymptomatic ones (6.85 years vs 2.03 years). The dorsolumbar and lumbar regions were most frequently involved and in three cases the cervical spine was affected. Weakness of lower limbs (n=37), muscle atrophy (n=23) and gait disturbance were the most common indicators of motor system involvement. The sensory complaints were mainly hypoesthesia (n=16), trophic ulcer (n=4) and autoamputation (n=3). Hypertrichiosis was the most common cutaneous marker present alone or in combination with other markers in 21 cases. MRI, done in all cases, correctly established the diagnosis. Additional lesions causing tethering were seen in 50% cases and were simultaneously treated. Associated Chiari malformation was seen in 12%. Of the 42 symptomatic patients, 21 improved, in 17 (40%) the neurological deficits stabilized and 4 showed deterioration. Cerebrospinal fluid fistula occurred in 4 patients and 3 had wound infections. Among the asymptomatic patients none had neurological deterioration postoperatively.

Split cord malformations are rare spinal cord disorders. Complete neural axis should be scanned at the first instance to determine associated lesions. Good results can be expected in about 90% patients with minimal complications 14).

Thirty-nine patients with split cord malformations (SCM) were studied in detail with respect to their clinical, radiographic, and surgical findings as well as their outcome data. Eight patients were adults and 31 patients were children. According to the classification endorsed by Part I of the SCM study, 19 patients had Type I SCM (6 adults and 13 children), 18 patients had Type II SCM (2 adults and 16 children), and 2 patients had composite SCM with both lesion types situated in tandem. Six SCMs were cervical, 2 were thoracic, and 31 were in the lumbar region. All 8 adults had pain and progressive sensorimotor deficits at diagnosis. Only 16 of the 31 children had symptoms, and among these, 14 had progressive sensorimotor deficits, but only 6 had pain. The difference in the clinical picture between adults and children is similar to that described in the tethered cord syndrome, except for left-right functional discrepancy, which was prominent in 8 children with SCM but rarely seen in tethered cord syndrome due to other causes. Cutaneous manifestations of either occult or open dysraphic states were present in all but 3 patients; hypertrichosis was by far the best predictor of an underlying SCM, being found in 56% in the series. Neurological deterioration in SCM was independent of the lesion type: the Type I:Type II ratio for symptomatic progression was 13:11. It was also independent of the location of the lesion: 67% of patients with cervical SCMs had symptomatic progression versus 64% of patients with thoracolumbar lesions. High-resolution, thin cut, axial computed tomographic myelography using bone algorithms was more sensitive than magnetic resonance imaging in defining the anatomical details of the SCM. Radiographic classifications of the SCM, using the nature of the median septum and the number of dural tubes as criteria, was always possible without ambiguity. However, whereas every Type I bone septum was identified preoperatively, only 5 Type II fibrous septa were revealed by preoperative imaging, even though a fibrous septum and/or other fibroneurovascular bands were found tethering the hemicords in every Type II case at surgery. Complete imaging studies also showed that all lumbar SCMs had low-lying coni and at least one additional tethering lesion besides the split cords, whereas only 1 of 7 cervical and high thoracic SCMs had a low conus and a second tethering lesion. The surgical goal for SCM was release of the tethered hemicords by eliminating the bone spurs, dural sleeves, fibrous septa, or any fibroneurovascular bands (myelomeningoceles manqué) that might be transfixing the split cord. Type I cases were technically more difficult and had a slightly higher surgical morbidity than Type II cases, especially if an oblique bone septum had asymmetrically divided the cord into one larger hemicord and one smaller, hence, very delicate, hemicord 15).

Case reports

Nazarali et al. reported on two patients who atypically presented with SCM in adulthood and reviewed previous reports 16).

A rare case of a child with a complex spina bifida with two different levels of split cord malformation (SCM) type 1 and single-level type 2, a nonterminal myelocystocele, coccygeal dermal sinus, bifid fatty filum and hydrocephalus, which substantiates the neurenteric canal theory and have further tried to highlight the importance of complete Magnetic resonance imaging (MRI) screening of the whole spine and brain with SCM to rule out other associated conditions. The patient was admitted with a leaking myelocystocele with bilateral lower limb weakness. MRI of the whole spine with a screening of brain was done. Patient underwent 5 operations in the same sitting- (According to classification given by Mahapatra et al.) removal of SCM type 1a at D7-8; removal of SCM type1c at L2-3; removal of SCM type 2 at D10; repair of nonterminal myelocystocele at D6-D10; low-pressure ventriculoperitoneal shunt on right side with excision of dermal coccygeal sinus; and, excision of bifid fatty filum. The clinic radiological findings in our patient further substantiate the multiple accessory neuroenteric canal theory in the development of a composite type of SCM. The physical and neurological signs of SCM and nonterminal myelocystocele should prompt the neurosurgeon to consider performing the screening MRI of the whole spine with the brain to rule out other composite types of SCM and hydrocephalus 17).

A 78-year-old woman presented for evaluation of back pain, urinary dysfunction, leg weakness and progressive equinovarus foot deformity. She reported that shortly after her birth in 1924, she underwent resection of a subcutaneous ‘cyst’ in the lower lumbar area. Seven years prior to evaluation at our institution, she had undergone bilateral total knee arthroplasty for osteoarthritis. After the procedure, she began to experience severe low back pain that radiated into her legs. Weakness of the foot inverters, urinary dysfunction and worsening bilateral equinovarus foot deformity developed in the years following the surgery. MRI revealed a split cord malformation with a tethered spinal cord. Because of the patient’s age and poor medical condition, her symptoms were managed conservatively. This case demonstrates symptomatic deterioration in an elderly patient with a tethered spinal cord after many years of clinical stability 18).

A 32-year-old man with the adult-onset of impairment of sacral functions with lumbar fibrous diastematomyelia is reported. Surgical release of the spinal cord was followed by improvement of the patient’s function 19).

References

1) , 6)

Pang D, Dias MS, Ahab-Barmada M. Split cord malformation: Part I: A unified theory of embryogenesis for double spinal cord malformations. Neurosurgery. 1992 Sep;31(3):451-80. Review. PubMed PMID: 1407428.
2)

Saker E, Loukas M, Fisahn C, Oskouian RJ, Tubbs RS. Historical Perspective of Split Cord Malformations: A Tale of Two Cords. Pediatr Neurosurg. 2017;52(1):1-5. PubMed PMID: 27806370.
3)

Pang D, Dias MS, Ahab-Barmada M. Split cord malformation: Part I. A unified theory of embryogenesis for double spinal cord malformations. Neurosurgery 1992;31:451-480.
4)

Pang D, Dias MS, Ahab-Barmada M. Split cord malformation. Part II: Clinical syndrome. Neurosurgery 1992;31:481-500.
5)

Sun M, Tao B, Luo T, Gao G, Shang A. We Are Cautious to Use the Term, ‘Split Cord Malformation Type 1.5’. J Korean Neurosurg Soc. 2022 Aug 22. doi: 10.3340/jkns.2022.0058. Epub ahead of print. PMID: 35989187.
7) , 8) , 11)

Mahapatra AK, Gupta DK. Split cord malformations: a clinical study of 254 patients and a proposal for a new clinical-imaging classification. J Neurosurg. 2005 Dec;103(6 Suppl):531-6. PubMed PMID: 16383252.
9)

Beuriat PA, Di Rocco F, Szathmari A, Mottolese C. Management of split cord malformation in children: the Lyon experience. Childs Nerv Syst. 2018 May;34(5):883-891. doi: 10.1007/s00381-018-3772-3. Epub 2018 Mar 26. Erratum in: Childs Nerv Syst. 2018 May 17;:. Pierre-Aurelien, Beuriat [corrected to Beuriat, Pierre-Aurélien]; Federico, Di Rocco [corrected to Di Rocco, Federico]; Alexandru, Szathmari [corrected to Szathmari, Alexandru]; Carmine, Mottolese [corrected to Mottolese, Carmine]. PubMed PMID: 29582170.
10)

Mahapatra AK. Split cord malformation – A study of 300 cases at AIIMS 1990-2006. J Pediatr Neurosci. 2011 Oct;6(Suppl 1):S41-5. doi: 10.4103/1817-1745.85708. PubMed PMID: 22069430; PubMed Central PMCID: PMC3208912.
12)

Kumar R, Bansal KK, Chhabra DK. Split cord malformation (scm) in paediatric patients: outcome of 19 cases. Neurol India. 2001 Jun;49(2):128-33. PubMed PMID: 11447430.
13)

Proctor MR, Scott RM. Long-term outcome for patients with split cord malformation. Neurosurg Focus. 2001 Jan 15;10(1):e5. PubMed PMID: 16749757.
14)

Jindal A, Mahapatra AK. Split cord malformations–a clinical study of 48 cases. Indian Pediatr. 2000 Jun;37(6):603-7. PubMed PMID: 10869139.
15)

Pang D. Split cord malformation: Part II: Clinical syndrome. Neurosurgery. 1992 Sep;31(3):481-500. Review. PubMed PMID: 1407429.
16)

Nazarali R, Lyon K, Cleveland J, Garrett D Jr. Split cord malformation associated with scoliosis in adults. Proc (Bayl Univ Med Cent). 2019 Mar 27;32(2):274-276. doi: 10.1080/08998280.2019.1573624. eCollection 2019 Apr. Review. PubMed PMID: 31191152; PubMed Central PMCID: PMC6541173.
17)

Khandelwal A, Tandon V, Mahapatra AK. An unusual case of 4 level spinal dysraphism: Multiple composite type 1 and type 2 split cord malformation, dorsal myelocystocele and hydrocephalous. J Pediatr Neurosci. 2011 Jan;6(1):58-61. doi: 10.4103/1817-1745.84411. PubMed PMID: 21977092; PubMed Central PMCID: PMC3173919.
18)

Pallatroni HF, Ball PA, Duhaime AC. Split cord malformation as a cause of tethered cord syndrome in a 78-Year-old female. Pediatr Neurosurg. 2004 Mar-Apr;40(2):80-3. PubMed PMID: 15292638.
19)

Chehrazi B, Haldeman S. Adult onset of tethered spinal cord syndrome due to fibrous diastematomyelia: case report. Neurosurgery. 1985 May;16(5):681-5. PubMed PMID: 3889701.

Craniopharyngioma (CP)

Craniopharyngioma (CP)

A craniopharyngioma (CP) is an embryonic malformation of the sellar region and parasellar region.

Its relation to Rathke’s cleft cyst (RCC) is controversial, and both lesions have been hypothesized to lie on a continuum of ectodermal cystic lesions of the sellar region.

Jakob Erdheim (1874-1937) was a Viennese pathologist who identified and defined a category of pituitary tumors known as craniopharyngiomas. He named these lesions “hypophyseal duct tumors” (Hypophysenganggeschwülste), a term denoting their presumed origin from cell remnants of the hypophyseal duct, the embryological structure through which Rathke’s pouch migrates to form part of the pituitary gland. He described the two histological varieties of these lesions as the adamantinomatous and the squamous-papillary types. He also classified the different topographies of craniopharyngiomas along the hypothalamus-pituitary axis. Finally, he provided the first substantial evidence for the functional role of the hypothalamus in the regulation of metabolism and sexual functions. Erdheim’s monograph on hypophyseal duct tumors elicited interest in the clinical effects and diagnosis of pituitary tumors. It certainly contributed to the development of pituitary surgery and neuroendocrinology. Erdheim’s work was greatly influenced by the philosophy and methods of research introduced to the Medical School of Vienna by the prominent pathologist Carl Rokitansky. Routine practice of autopsies in all patients dying at the Vienna Municipal Hospital (Allgemeines Krankenhaus), as well as the preservation of rare pathological specimens in a huge collection stored at the Pathological-Anatomical Museum, represented decisive policies for Erdheim’s definition of a new category of epithelial hypophyseal growths. Because of the generalized use of the term craniopharyngioma, which replaced Erdheim’s original denomination, his seminal work on hypophyseal duct tumors is only referenced in passing in most articles and monographs on this tumor.

Jakob Erdheim should be recognized as the true father of craniopharyngiomas 1).

Epidemiology

Craniopharyngioma epidemiology.

Origin

Its relation to Rathke’s cleft cyst (RCC) is controversial, and both lesions have been hypothesized to lie on a continuum of cystic ectodermal lesions of the sellar region.

It grows close to the optic nerve, hypothalamus and pituitary gland.

Craniopharyngiomas frequently grow from remnants of the Rathke pouch, which is located on the cisternal surface of the hypothalamic region. These lesions can also extend elsewhere in the infundibulohypophyseal axis.

These tumors can also grow from the infundibulum or tuber cinereum on the floor of the third ventricle, developing exclusively into the third ventricle.

Classification

Craniopharyngioma Classification.

Molecular and genetic markers

Genetic and immunological markers show variable expression in different types of Craniopharyngioma. BRAF is implicated in tumorigenesis in papillary Craniopharyngioma (pCP), whereas CTNNB1 and EGFR are often overexpressed in adamantinomatous Craniopharyngioma (aCP) and VEGF is overexpressed in aCP and Craniopharyngioma recurrence. Targeted treatment modalities inhibiting thesepathways can shrink or halt progression of CP. In addition, Epidermal growth factor receptor tyrosine kinase inhibitors may sensitize tumors to radiation therapy. These – drugs show promise in medical management and neoadjuvant therapy for CP. Immunotherapy, including anti-interleukin 6 (IL-6) drugs and interferon treatment, are also effective in managing tumor growth. Ongoing – clinical trials in CP are limited but are testing BRAF/MET inhibitors and IL-6 monoclonal antibodies.

Genetic and immunological markers show variable expression in different subtypes of CP. Several current molecular treatments have shown some success in the management of this disease. Additional clinical trials and targeted therapies will be important to improve CP patient outcomes 2).

Craniopharyngioma Natural History

Craniopharyngioma natural history.

Clinical Features

see Craniopharyngioma Clinical Features.

Diagnosis

see Craniopharyngioma Diagnosis.

Differential diagnosis

Rathke’s cleft cyst.

ependymoma, pilocytic astrocytoma, choroid plexus papilloma (CPP), craniopharyngioma, primitive neuroectodermal tumor (PNET), choroid plexus carcinoma (CPC), immature teratoma, atypical teratoid rhabdoid tumor (AT/RT), anaplastic astrocytoma, and gangliocytoma.

Compared with craniopharyngiomas, sellar gliomas presented with a significantly lower ratio of visual disturbances, growth hormone deficiencies, lesion cystic changes, and calcification. Sellar gliomas had significantly greater effects on the patients’ mentality and anatomical brain stem involvement 3).

Co-occurrence

Simultaneous sellar-suprasellar craniopharyngioma and intramural clival chordoma, successfully treated by a single staged, extended, fully endoscopic endonasal approach, which required no following adjuvant therapy is reported 4).

Treatment

see Craniopharyngioma treatment

Outcome

see Craniopharyngioma outcome

Books

Craniopharyngioma: Surgical Treatment.

10 Selected Works

Craniopharyngioma Selected Works.

Case series

see Craniopharyngioma case series.

Case reports

see Craniopharyngioma case reports.

Videos

Craniopharyngioma Videos

1)

Pascual JM, Rosdolsky M, Prieto R, Strauβ S, Winter E, Ulrich W. Jakob Erdheim (1874-1937): father of hypophyseal-duct tumors (craniopharyngiomas). Virchows Arch. 2015 Jun 19. [Epub ahead of print] PubMed PMID: 26089144.
2)

Reyes M, Taghvaei M, Yu S, Sathe A, Collopy S, Prashant GN, Evans JJ, Karsy M. Targeted Therapy in the Management of Modern Craniopharyngiomas. Front Biosci (Landmark Ed). 2022 Apr 20;27(4):136. doi: 10.31083/j.fbl2704136. PMID: 35468695.
3)

Deng S, Li Y, Guan Y, Xu S, Chen J, Zhao G. Gliomas in the Sellar Turcica Region: A Retrospective Study Including Adult Cases and Comparison with Craniopharyngioma. Eur Neurol. 2014 Dec 18;73(3-4):135-143. [Epub ahead of print] PubMed PMID: 25531372.
4)

Iacoangeli M, Rienzo AD, Colasanti R, Scarpelli M, Gladi M, Alvaro L, Nocchi N, Scerrati M. A rare case of chordoma and craniopharyngioma treated by an endoscopic endonasal, transtubercular transclival approach. Turk Neurosurg.2014;24(1):86-9. doi: 10.5137/1019-5149.JTN.7237-12.0. PubMed PMID: 24535799.

SMAD6

SMAD6

(SMAD Family Member 6) is a Protein Coding gene.

It belongs to the SMAD family of signaling molecules. It acts as an inhibitory SMAD, meaning that it negatively regulates signaling pathways activated by transforming growth factor-beta (TGF-beta) and bone morphogenetic proteins (BMPs). SMAD6 plays a role in various biological processes such as cell proliferation, differentiation, and apoptosis,

SMAD6 encodes an intracellular inhibitor of the bone morphogenetic protein (BMP) signaling pathway. Until now, SMAD6 deficiency has been associated with three distinctive human congenital conditions, i.e., congenital heart diseases, including left ventricular obstruction and conotruncal defects, craniosynostosis, and radioulnar synostosis. Intriguingly, a similar spectrum of heterozygous loss-of-function variants has been reported to cause these clinically distinct disorders without a genotype-phenotype correlation. Even identical nucleotide changes have been described in patients with either a cardiovascular phenotype, craniosynostosis or radioulnar synostosis. These findings suggest that the primary pathogenic variant alone cannot explain the resultant patient phenotype 1).

SMAD6 mutations led to poorer mathematics, performance intelligence quotient, full-scale intelligence quotient, and motor coordination, even after controlling for exogenous factors. Genetic testing may be critical for advocating early adjunctive neurodevelopmental therapy 2)

Mechanisms to explain the remarkable diversity of phenotypes associated with SMAD6 variants remain obscure 3).

Among 101 infants tested in the Department of Pediatric Neurosurgery, French Referral Center for Craniosynostosis, Hôpital Femme Mère-Enfant Hospices Civils de Lyon, University of Lyon, Department of Genetics, Lyon University Hospitals, INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, Department of Pediatric Cranio-Maxillo-Facial Surgery, Hôpital Femme Mère Enfant, Université Claude Bernard Lyon 1, Lyon, and Department of Genetics, Robert Debré Hospital, Inserm 1132, Université de Paris Cité, Paris, France, 13 carried a total of 13 variants; that is, 12.9% of the infants carried a variant in genes known to be involved in craniosynostosis. Seven infants carried SMAD6 variants, 2 in FGFR2, 1 in TWIST1, one in FREM1, one in ALX4, and one in TCF12. All variants were detected at the heterozygous level in genes associated with autosomal dominant craniosynostosis. Also, neurodevelopmental testing showed especially delayed acquisition of language in children with than without variants in SMAD6. In conclusion, a high percentage of young children with isolated midline craniosynostosis, especially in isolated trigonocephaly, carried SMAD6 variants. The interpretation of the pathogenicity of the genes must take into account incomplete penetrance, usually observed in craniosynostosis. The results highlight the interest in molecular analysis in the context of isolated sagittal and/or metopic craniosynostosis to enhance an understanding of the pathophysiology of midline craniosynostosis 4).

1)

Luyckx I, Verstraeten A, Goumans MJ, Loeys B. SMAD6-deficiency in human genetic disorders. NPJ Genom Med. 2022 Nov 21;7(1):68. doi: 10.1038/s41525-022-00338-5. PMID: 36414630; PMCID: PMC9681871.
2)

Wu RT, Timberlake AT, Abraham PF, Gabrick KS, Lu X, Peck CJ, Sawh-Martinez RF, Steinbacher DM, Alperovich MA, Persing JA. SMAD6 Genotype Predicts Neurodevelopment in Nonsyndromic Craniosynostosis. Plast Reconstr Surg. 2020 Jan;145(1):117e-125e. doi: 10.1097/PRS.0000000000006319. PMID: 31592950.
3)

Calpena E, Cuellar A, Bala K, Swagemakers SMA, Koelling N, McGowan SJ, Phipps JM, Balasubramanian M, Cunningham ML, Douzgou S, Lattanzi W, Morton JEV, Shears D, Weber A, Wilson LC, Lord H, Lester T, Johnson D, Wall SA, Twigg SRF, Mathijssen IMJ, Boardman-Pretty F; Genomics England Research Consortium; Boyadjiev SA, Wilkie AOM. SMAD6 variants in craniosynostosis: genotype and phenotype evaluation. Genet Med. 2020 Sep;22(9):1498-1506. doi: 10.1038/s41436-020-0817-2. Epub 2020 Jun 5. Erratum in: Genet Med. 2020 Jul 7;: PMID: 32499606; PMCID: PMC7462747.
4)

Di Rocco F, Rossi M, Verlut I, Szathmari A, Beuriat PA, Chatron N, Chauvel-Picard J, Mottolese C, Monin P, Vinchon M, Guernouche S, Collet C. Clinical interest of molecular study in cases of isolated midline craniosynostosis. Eur J Hum Genet. 2023 Feb 3. doi: 10.1038/s41431-023-01295-y. Epub ahead of print. PMID: 36732661.

Cerebellar mutism

Cerebellar mutism

Cerebellar mutism (CM) was first described by Rekate et al. in 1985 following posterior fossa surgery in children 1) ;since then, it has increasingly been reported, mainly occurring as a postoperative complication.

Posterior fossa syndrome (PFS) and cerebellar mutism are often used interchangeably in the literature.

Epidemiology

Incidence of cerebellar mutism: 11–29% of children following surgery for cerebellar tumors 2) including cerebellar medulloblastoma (53%), posterior fossa ependymoma (33%) & cerebellar pilocytic astrocytoma (11%) 3).

Etiology

It has also been reported in both children and adults following several other cerebellar insults, including vascular events, infections, and trauma 4).

The uncertain etiology of PFS, myriad of cited risk factors and therapeutic challenges make this phenomenon an elusive entity.

Risk Factors

Cerebellar mutism risk factors

Posttraumatic cerebellar mutism

Cerebellar mutism is a rare occurrence following paediatric trauma 5) 6) 7) 8). , this phenomenon has rarely been reported following other insults, such as trauma, and its pathophysiology remains poorly understood.

A seven-year-old child who presented to the casualty department of Sultan Qaboos University Hospital in Muscat, Oman, in May 2013 with a traumatic right cerebellar contusion. The child presented with clinical features of cerebellar mutism but underwent a rapid and spontaneous recovery 9).

Pathophysiology

Cerebellar mutism Pathophysiology.

Pathogenesis

The pathogenic mechanism is likely due to the damage occurring to the proximal efferent cerebellar pathway, including the dentate nucleus, the superior cerebellar peduncle, and its decussation in the mesencephalic tegmentum 10).

Superior and inferior cerebellar peduncles and the superior part of the cerebellum were related to CMS, especially the right side 11).

Clinical features

This syndrome involves a variety of signs and symptoms including cerebellar mutism or speech disturbances, dysphagia, decreased motor movement, cranial nerve palsy and, emotional lability. These signs and symptoms develop from an average range of 24 to 107 hours after surgery and may take weeks to months to resolve.

Diagnosis

Multi-inflow time arterial spin-labeling shows promise as a noninvasive tool to evaluate cerebral perfusion in the setting of pediatric obstructive hydrocephalus and demonstrates increased CBF following the resolution of cerebellar mutism syndrome 12).

Differential diagnosis

The importance of olivary hypertrophic degeneration as a differential diagnosis in cerebellar mutism syndrome 13).

Prevention

Cerebellar mutism prevention.

Outcome

Early recognition of this syndrome could facilitate preventive and restorative patient care, prevent subsequent complications, decrease length of hospital stays, and promote patient and family understanding of and coping with the syndrome 14).

Case series

20 cases of PFS (8%), 12 males and 8 females. Age ranged from 1.5 to 13 years (mean = 6.5). Of the 20, 16 were medulloblastoma, 3 ependymoma and 1 astrocytoma. There was a 21 % incidence (16/76) of PFS in medulloblastoma of the posterior fossa. The incidence for ependymoma was 13% (3/24) and 1% (1/102) for astrocytoma. All 20 cases (100%) had brainstem involvement by the tumor. The most frequent postoperative findings included mutism, ataxia, 6th and 7th nerve palsies and hemiparesis. Mutism had a latency range of 1-7 days (mean = 1.7) and a duration of 6-365 days (mean = 69.2, median = 35). Although mutism resolved in all cases, the remaining neurologic complications which characterized our findings of PFS were rarely reversible. We describe potential risk factors for developing PFS after surgery with hopes of making neurosurgeons more aware of potential problems following the removal of lesions in this area. Early recognition of PFS would further promote patient and family understanding and coping with this síndrome 15)

19 children diagnosed with posterior fossa syndrome 16)

Case reports

Cerebellar mutism case reports.

1)

Rekate HL, Grubb RL, Aram DM, Hahn JF, Ratcheson RA. Muteness of cerebellar origin. Arch Neurol. 1985;42:697–8. doi: 10.1001/archneur.1985.04060070091023.
2)

Gudrunardottir T, Sehested A, Juhler M, et al. Cerebellar mutism: review of the literature. Childs Nerv Syst. 2011; 27:355–363
3)

Catsman-Berrevoets C E, Van Dongen HR, Mulder PG, et al. Tumour type and size are high risk factors for the syndrome of “cerebellar” mutism and subsequent dysarthria. J Neurol Neurosurg Psychiatry. 1999; 67:755–757
4)

Gudrunardottir T, Sehested A, Juhler M, Schmiegelow K. Cerebellar mutism: Review of the literature. Childs Nerv Syst. 2011;27:355–63. doi: 10.1007/s00381-010-1328-2.
5)

Erşahin Y, Mutluer S, Saydam S, Barçin E. Cerebellar mutism: Report of two unusual cases and review of the literature. Clin Neurol Neurosurg. 1997;99:130–4. doi: 10.1016/S0303-8467(97)80010-8.
6)

Fujisawa H, Yonaha H, Okumoto K, Uehara H, le T, Nagata Y, et al. Mutism after evacuation of acute subdural hematoma of the posterior fossa. Childs Nerv Syst. 2005;21:234–6. doi: 10.1007/s00381-004-0999-y.
7)

Koh S, Turkel SB, Baram TZ. Cerebellar mutism in children: Report of six cases and potential mechanisms. Pediatr Neurol. 1997;16:218–19. doi: 10.1016/S0887-8994(97)00018-0.
8)

Yokota H, Nakazawa S, Kobayashi S, Taniguchi Y, Yukihide T. [Clinical study of two cases of traumatic cerebellar injury] No Shinkei Geka. 1990;18:67–70.
9)

Kariyattil R, Rahim MI, Muthukuttiparambil U. Cerebellar mutism following closed head injury in a child. Sultan Qaboos Univ Med J. 2015 Feb;15(1):e133-5. Epub 2015 Jan 21. PubMed PMID: 25685374; PubMed Central PMCID: PMC4318595.
10)

Fabozzi F, Margoni S, Andreozzi B, Musci MS, Del Baldo G, Boccuto L, Mastronuzzi A, Carai A. Cerebellar mutism syndrome: From pathophysiology to rehabilitation. Front Cell Dev Biol. 2022 Dec 2;10:1082947. doi: 10.3389/fcell.2022.1082947. PMID: 36531947; PMCID: PMC9755514.
11)

Yang W, Li Y, Ying Z, Cai Y, Peng X, Sun H, Chen J, Zhu K, Hu G, Peng Y, Ge M. A presurgical voxel-wise predictive model for cerebellar mutism syndrome in children with posterior fossa tumors. Neuroimage Clin. 2022 Dec 13;37:103291. doi: 10.1016/j.nicl.2022.103291. Epub ahead of print. PMID: 36527996; PMCID: PMC9791171.
12)

Toescu SM, Hales PW, Cooper J, Dyson EW, Mankad K, Clayden JD, Aquilina K, Clark CA. Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery. AJNR Am J Neuroradiol. 2022 Oct;43(10):1508-1515. doi: 10.3174/ajnr.A7637. Epub 2022 Sep 22. PMID: 36137658; PMCID: PMC9575521.
13)

Ballestero M, de Oliveira RS. The importance of olivary hypertrophic degeneration as a differential diagnosis in cerebellar mutism syndrome. Childs Nerv Syst. 2022 Dec 21. doi: 10.1007/s00381-022-05815-x. Epub ahead of print. PMID: 36542117.
14) , 16)

Kirk EA, Howard VC, Scott CA. Description of posterior fossa syndrome in children after posterior fossa brain tumor surgery. J Pediatr Oncol Nurs. 1995 Oct;12(4):181-7. PubMed PMID: 7495523.
15)

Doxey D, Bruce D, Sklar F, Swift D, Shapiro K. Posterior fossa syndrome: identifiable risk factors and irreversible complications. Pediatr Neurosurg. 1999 Sep;31(3):131-6. PubMed PMID: 10708354.

Anterior sacral meningocele

Anterior sacral meningocele

Anterior sacral meningoceles are congenital lesions that consist of a spinal fluid-filled sac in the pelvis communicating by a small neck with the spinal subarachnoid space through a defect in the sacrum. They protrude into retroperitoneal and presacral space. 1) 2).

The wall of the sac consists of two layers, an inner arachnoid membrane and outer dura mater, which extends into the retroperitoneal presacral space from the sacral spinal canal 3).

Anterior sacral meningocele was first described in 1837 as a part of neural tube defect (NTD) spectrum.

It may be associated with a syndrome like Currarino syndrome 4) which includes anorectal malformations, sacral bony defect and presacral mass; and Marfan syndrome wherein the etiology may be disorder of collagen biosynthesis and structure at the dural level 5).

Epidemiology

Anterior sacral meningocele epidemiology

Anterior sacral meningocele in Marfan syndrome

Anterior sacral meningocele in Marfan syndrome

Classification

Anterior sacral meningocele classification.

Etiology

Anterior sacral meningocele etiology.

Pathology

Associated malformations are found:

spina bifida

spinal dysraphism

bicornuate uterus

imperforate anus 6).

Clinical features

Anterior sacral meningocele clinical features.

Diagnosis

Anterior sacral meningocele diagnosis.

Differential diagnosis

Anterior sacral meningocele differential diagnosis.

Complications

Anterior sacral meningocele complications.

Treatment

Anterior Sacral Meningocele Treatment.

Case reports

Anterior sacral meningocele case reports.

1)

Villarejo F, Scavone C, Blazquez MG, Pascual-Castroviejo I, Perez-Higueras A, Fernandez-Sanchez A, Garcia Bertrand C. Anterior sacral meningocele: review of the literature. Surg Neurol. 1983 Jan;19(1):57-71. doi: 10.1016/0090-3019(83)90212-4. PMID: 6828997.
2)

Sharma V, Mohanty S, Singh DR. Uncommon craniospinal dysraphism. Ann Acad Med Singap. 1996 Jul;25(4):602-8. PMID: 8893940.
3)

Somuncu S, Aritürk E, Iyigün O, Bernay F, Rizalar R, Günaydin M, Gürses N. A case of anterior sacral meningocele totally excised using the posterior sagittal approach. J Pediatr Surg. 1997 May;32(5):730-2. doi: 10.1016/s0022-3468(97)90018-x. PMID: 9165463.
4)

CALIHAN RJ. Anterior sacral meningocele. Radiology. 1952 Jan;58(1):104-8. doi: 10.1148/58.1.104. PMID: 14883380.
5)

North RB, Kidd DH, Wang H. Occult, bilateral anterior sacral and intrasacral meningeal and perineurial cysts: case report and review of the literature. Neurosurgery. 1990 Dec;27(6):981-6. doi: 10.1097/00006123-199012000-00020. PMID: 2274142.
6)

Dahan H, Arrivé L, Wendum D, Docou le Pointe H, Djouhri H, Tubiana JM. Retrorectal developmental cysts in adults: clinical and radiologic-histopathologic review, differential diagnosis, and treatment. Radiographics. 2001 May-Jun;21(3):575-84. doi: 10.1148/radiographics.21.3.g01ma13575. PMID: 11353107.

Cerebellar pilocytic astrocytoma

Cerebellar pilocytic astrocytoma

Latest news

Key concepts

● Often cystic, half of these have a mural nodule.

● Usually presents during the second decade of life (ages 10–20 yrs).

● A subtype of pilocytic astrocytoma. Formerly referred to by the nonspecific and confusing term cystic cerebellar astrocytoma.

Epidemiology

Cerebellar pilocytic astrocytoma epidemiology.

Classification

Children

see Cerebellar pilocytic astrocytoma in children.

Adult

Cerebellar pilocytic astrocytomas in adults should be treated with macroscopic complete surgical resection whenever possible. If this is achieved, long-term survival rates are excellent, whereas subtotal resection carries a high risk of tumor recurrence. Ki67 is less important prognostically than the extent of initial resection 1).

Clinical features

In the posterior fossa tumors, there is predominantly a mass effect with signs of raised intracranial pressure, especially when hydrocephalus is present. Bulbar palsy or cerebellar syndrome may also be present.

Diagnosis

Cerebellar pilocytic astrocytoma diagnosis.

Differential diagnosis

Cerebellar pilocytic astrocytoma differential diagnosis.

Treatment

see Cerebellar pilocytic astrocytoma treatment.

Outcome

Nine percent of the children in a study underwent repeated surgery due to progressive tumor recurrence, and 15% were treated for persistent hydrocephalus 2).

The long-term functional outcome of low-grade cerebellar astrocytoma is generally favourable, in the absence of post-operative complications and brainstem involvement. No major impact of neurological deficits, cognitive functions and emotional disorders on academic achievement and independent functioning was observed 3).

The good long-term outcomes suggest that it may be appropriate to do incomplete resection rather than risk additional neurological deficit 4).

There is controversy about whether patients with tumor remaining after surgery should receive radiation therapy. It is also unclear whether only patients with incomplete resection require follow-up and for how long 5).

Complications

Acute hemorrhagic presentation in pilocytic astrocytomas (PAs) has become increasingly recognized. This type of presentation poses a clinically emergent situation in those hemorrhages arising in PAs of the cerebellum, the most frequent site, because of the limited capacity of the posterior fossa to compensate for mass effect, predisposing to rapid neurological deterioration.

Complete resection

Complete resection of cerebellar astrocytoma is an important prognostic factor, indicating a more favorable prognosis than subtotal resection. This was also the conclusion of a much larger study by Villarejo et al. who reviewed 203 cases of low-grade cerebellar astrocytoma 6).

Loh et al., documented that patients with subtotal removal of cerebellar astrocytoma can have arrested tumor growth or spontaneous tumor regression during long-term follow-up. Following partial resection of pediatric cerebellar astrocytoma, they recommend that the patients be followed up a “wait and see” approach with surveillance using MRI. They found that several tumors treated with radiotherapy after surgery had malignant transformation and do not recommend adjuvant radiation treatment for children with cerebellar astrocytoma who have subtotal resection. More research is needed on the prognosis of patients with subtotal resection of cerebellar astrocytoma 7).

Pilomyxoid features and anaplasia

A subset may behave in a more aggressive fashion and clinically progress despite the use of conventional treatments. Histologic features associated with a more aggressive course include the presence of monomorphous pilomyxoid features (ie, pilomyxoid variant) and anaplasia in the form of brisk mitotic activity with or without necrosis 8).

Case series

Cerebellar pilocytic astrocytoma case series.

Case reports

Cerebellar pilocytic astrocytoma case reports.

References

1) 

Wade A, Hayhurst C, Amato-Watkins A, Lammie A, Leach P. Cerebellar pilocytic astrocytoma in adults: a management paradigm for a rare tumour. Acta Neurochir (Wien). 2013 Aug;155(8):1431-5. doi: 10.1007/s00701-013-1790-1. Epub 2013 Jun 22. PubMed PMID: 23793962.

2) 

Due-Tønnessen BJ, Lundar T, Egge A, Scheie D. Neurosurgical treatment of low-grade cerebellar astrocytoma in children and adolescents: a single consecutive institutional series of 100 patients. J Neurosurg Pediatr. 2013 Mar;11(3):245-9. doi: 10.3171/2012.11.PEDS12265. Epub 2012 Dec 14. PubMed PMID: 23240848.

3) 

Ait Khelifa-Gallois N, Laroussinie F, Puget S, Sainte-Rose C, Dellatolas G. Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood. Brain Inj. 2014 Nov 10:1-8. [Epub ahead of print] PubMed PMID: 25383654.

4) 

Steinbok P, Mangat JS, Kerr JM, Sargent M, Suryaningtyas W, Singhal A, Cochrane D. Neurological morbidity of surgical resection of pediatric cerebellar astrocytomas. Childs Nerv Syst. 2013 Aug;29(8):1269-75. doi: 10.1007/s00381-013-2171-z. Epub 2013 May 29. PubMed PMID: 23715810.

5) 

Dirven CM, Mooij JJ, Molenaar WM. Cerebellar pilocytic astrocytoma: a treatment protocol based upon analysis of 73 cases and a review of the literature. Childs Nerv Syst. 1997;13:17–23. doi: 10.1007/s003810050033.

6) 

Villarejo F, Diego JMB, Riva AG. Prognosis of cerebellar astrocytoma in children. Childs Nerv Syst. 2008;24:203–210. doi: 10.1007/s00381-007-0449-8.

7) 

Loh JK, Lieu AS, Chai CY, Hwang SL, Kwan AL, Wang CJ, Howng SL. Arrested growth and spontaneous tumor regression of partially resected low-grade cerebellar astrocytomas in children. Childs Nerv Syst. 2013 Nov;29(11):2051-5. doi: 10.1007/s00381-013-2113-9. Epub 2013 May 1. PubMed PMID: 23632690; PubMed Central PMCID: PMC3825417.

8) 

Rodriguez FJ, Scheithauer BW, Burger PC, Jenkins S, Giannini C. Anaplasia in pilocytic astrocytoma predicts aggressive behavior. Am J Surg Pathol. 2010;34(2):147–160.

Pediatric traumatic brain injury outcome

Pediatric traumatic brain injury outcome

see also Traumatic brain injury outcome.

Latest articles

Neuropsychological and behavioral outcomes for injured children vary with the severity of the injury, child age at injury, premorbid child characteristics, family factors, and the family’s socioeconomic status. Each of these factors needs to be taken into account when designing rehabilitation strategies and assessing factors related to outcomes 1)

The Functional Status Score (FSS) can be implemented as part of routine practice in two different healthcare systems and the relationships observed between the FSS and patient characteristics can serve as a baseline for work going forward in the coming years. As a field, establishing which outcomes tests can be readily administered while also measuring relevant outcomes for various populations of children with TBI is an essential next step in developing therapies for this disorder that is highly prevalent and morbid 2).

The multi-center, prospectively collected CENTER-TBI core and registry databases were screened and patients were included when younger than 18 years at enrollment and admitted to the regular ward (admission stratum) or intensive care unit (ICU stratum) following TBI. Patient demographics, injury causes, clinical findings, brain CT imaging details, and outcome (GOSE at 6 months follow-up) were retrieved and analyzed. Injury characteristics were compared between patients admitted to the regular ward and ICU and a multivariate analysis of factors predicting an unfavorable outcome (GOSE 1-4) was performed. Results from the core study were compared to the registry dataset which includes larger patient numbers but no follow-up data. Results: Two hundred and twenty-seven patients in the core dataset and 687 patients in the registry dataset were included in this study. In the core dataset, road-traffic incidents were the most common cause of injury overall and in the ICU stratum, while incidental falls were most common in the admission stratum. Brain injury was considered serious to severe in the majority of patients and concurrent injuries in other body parts were very common. Intracranial abnormalities were detected in 60% of initial brain CTs. Intra- and extracranial surgical interventions were performed in one-fifth of patients. The overall mortality rate was 3% and the rate of unfavorable outcomes was 10%, with those numbers being considerably higher among ICU patients. GCS and the occurrence of secondary insults could be identified as independent predictors of an unfavorable outcome 3).

There are few specific prognostic models specifically developed for the pediatric traumatic brain injury (TBI) population.

Fang et al. aimed to combine multiple machine learning approaches to building hybrid models for predicting the prognosis and length of hospital stay for adults and children with TBI.

They collected relevant clinical information from patients treated at the Neurosurgery Center of the Second Affiliated Hospital of Anhui Medical University between May 2017 and May 2022, of which 80% was used for training the model and 20% for testing via screening and data splitting. They trained and tested the machine learning models using 5 cross-validations to avoid overfitting. In the machine learning models, 11 types of independent variables were used as input variables and the Glasgow Outcome Scale score, was used to evaluate patients’ prognosis, and patient length of stay was used as the output variable. Once the models were trained, we obtained and compared the errors of each machine-learning model from 5 rounds of cross-validation to select the best predictive model. The model was then externally tested using clinical data of patients treated at the First Affiliated Hospital of Anhui Medical University from June 2021 to February 2022.

Results: The final convolutional neural network-support vector machine (CNN-SVM) model predicted the Glasgow Outcome Scale score with an accuracy of 93% and 93.69% in the test and external validation sets, respectively, and an area under the curve of 94.68% and 94.32% in the test and external validation sets, respectively. The mean absolute percentage error of the final built convolutional neural network-support vector regression (CNN-SVR) model predicting inpatient time in the test set and external validation set was 10.72% and 10.44%, respectively. The coefficient of determination (R2) was 0.93 and 0.92 in the test set and external validation set, respectively. Compared with a back-propagation neural network, CNN, and SVM models built separately, our hybrid model was identified to be optimal and had high confidence.

This study demonstrates the clinical utility of 2 hybrid models built by combining multiple machine learning approaches to accurately predict the prognosis and length of stay in hospital for adults and children with TBI. Application of these models may reduce the burden on physicians when assessing TBI and assist clinicians in the medical decision-making process 4).

Mikkonen et al., tested the predictive performance of existing prognostic tools, originally developed for the adult TBI population, in pediatric TBI patients requiring stays in the ICU.

They used the Finnish Intensive Care Consortium database to identify pediatric patients (< 18 years of age) treated in 4 academic ICUs in Finland between 2003 and 2013. They tested the predictive performance of 4 classification systems-the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) TBI model, the Helsinki CT score, the Rotterdam CT score, and the Marshall CT classification-by assessing the area under the receiver operating characteristic curve (AUC) and the explanatory variation (pseudo-R2 statistic). The primary outcome was 6-month functional outcome (favorable outcome defined as a Glasgow Outcome Scale score of 3-5).

Overall, 341 patients (median age 14 years) were included; of these, 291 patients had primary head CT scans available. The IMPACT core-based model showed an AUC of 0.85 (95% CI 0.78-0.91) and a pseudo-R2 value of 0.40. Of the CT scoring systems, the Helsinki CT score displayed the highest performance (AUC 0.84, 95% CI 0.78-0.90; pseudo-R2 0.39) followed by the Rotterdam CT score (AUC 0.80, 95% CI 0.73-0.86; pseudo-R2 0.34).

Prognostic tools originally developed for the adult TBI population seemed to perform well in pediatric TBI. Of the tested CT scoring systems, the Helsinki CT score yielded the highest predictive value 5).

1)

Keenan HT, Bratton SL. Epidemiology and outcomes of pediatric traumatic brain injury. Dev Neurosci. 2006;28(4-5):256-63. doi: 10.1159/000094152. PMID: 16943649.
2)

Bell MJ. Outcomes for Children With Traumatic Brain Injury-How Can the Functional Status Scale Contribute? Pediatr Crit Care Med. 2016 Dec;17(12):1185-1186. doi: 10.1097/PCC.0000000000000950. PMID: 27918390; PMCID: PMC5142208.
3)

Riemann L, Zweckberger K, Unterberg A, El Damaty A, Younsi A; Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Investigators and Participants. Injury Causes and Severity in Pediatric Traumatic Brain Injury Patients Admitted to the Ward or Intensive Care Unit: A Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study. Front Neurol. 2020 Apr 30;11:345. doi: 10.3389/fneur.2020.00345. PMID: 32425879; PMCID: PMC7205018.
4)

Fang C, Pan Y, Zhao L, Niu Z, Guo Q, Zhao B. A Machine Learning-Based Approach to Predict Prognosis and Length of Hospital Stay in Adults and Children With Traumatic Brain Injury: Retrospective Cohort Study. J Med Internet Res. 2022 Dec 9;24(12):e41819. doi: 10.2196/41819. PMID: 36485032.
5)

Mikkonen ED, Skrifvars MB, Reinikainen M, Bendel S, Laitio R, Hoppu S, Ala-Kokko T, Karppinen A, Raj R. Validation of prognostic models in intensive care unit-treated pediatric traumatic brain injury patients. J Neurosurg Pediatr. 2019 Jun 7:1-8. doi: 10.3171/2019.4.PEDS1983. [Epub ahead of print] PubMed PMID: 31174193.