Pediatric Epilepsy Surgery Preoperative Assessment and Surgical Treatment

Pediatric Epilepsy Surgery Preoperative Assessment and Surgical Treatment

by Oguz Cataltepe (Author), George Jallo (Author)

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The definitive guide to surgical management of epilepsy in pediatric patients

This fully revised and updated second edition of Pediatric Epilepsy Surgery, edited by internationally renowned pediatric neurosurgeons and epilepsy surgery experts Oğuz Çataltepe and George Jallo, fills a void in the literature, encompassing the full spectrum of topics related to the surgical treatment of intractable epilepsy and seizures in children. The prodigiously illustrated book and its accompanying videos feature contributions from distinguished specialists in several different countries across a wide range of disciplines.

From epidemiology, genetics, pathology, preoperative electrophysiological assessment and neuroimaging to state-of-the-art surgical approaches, this remarkable resource covers the full depth and breadth of surgical management of pediatric epilepsy. Topics include awake anesthesia, intracranial stimulation and mapping techniques, temporal and extratemporal epilepsy surgery techniques, insular, multilobar and hemispheric surgery approaches, and diverse disconnection, neuromodulation, and ablative procedures. Insights are provided on postoperative issues including seizure control, neuropsychological and psychosocial outcomes, surgical failure and re-operation, and much more.

Key Features

A review of topographic anatomy of the cerebral cortex and white matter with numerous illustrations provides enhanced understanding of eloquent anatomy. Discussion of cutting-edge techniques such as stereo-electroencephalography, multi-modality imaging and tractography, endoscopic and laser ablation approaches in hypothalamic hamartomas, peri-insular quadrantotomy, and various hemispherotomy approaches. Overview of common cortical stimulation and mapping techniques including magnetic and electrical stimulation modalities, functional MRI, and the WADA test. 13 videos demonstrate seizure semiology, stimulation, awake surgery, hemispherotomy, amygdalohippocampectomy, and endoscopic corpus callosotomy. This state-of-the-art resource is a must-have for epilepsy surgeons and epileptologists. It will also greatly benefit neurosurgeons, neurologists, clinical neuropsychologists, electrophysiologists, neuroradiologists, residents, fellows, and medical students involved in the assessment and surgical management of epilepsy in pediatric patients.

This book includes complimentary access to a digital copy on https://medone.thieme.com.

Myelomeningocele complications

Myelomeningocele complications

Associated problems include poor ability to walk, problems with bladder or bowel control, hydrocephalus, a tethered spinal cord, and latex allergy.

Closure of a myelomeningocele is a deceptively simple operation; however, attention to several subtle details can significantly reduce operative complications. Important preoperative concerns include social issues of dealing with a distraught and often overwhelmed family, the timing of surgery, and assessment of associated severe or life-threatening malformations. Operative intervention should be directed toward preserving neurological function and optimizing the subsequent repair of a tethered spine should this become necessary. Careful attention to the vascular supply to the placode, precise separation of neural from cutaneous tissues, a diligent search for associated tethering anomalies such as diastematomyelia and a thickened filum terminale, careful pia to pia reconstruction of the placode, and simple but meticulous wound closure all help in achieving these aims. The timely management of associated hydrocephalus will help to avoid cerebrospinal fluid leakage and wound dehiscence. Close attention to these details will ameliorate many of the immediate and delayed complications of myelomeningocele closure 1).


Patients with Myelomeningocele (MMC) have multiple risk factors for venous thrombosis, but this complication rarely occurs. This lower rate of venous thrombosis in MMC children could be related to some characteristics of the vessels in the lower extremities. A study of Salari et al. aimed at finding explanations for this dilemma.

A case control study was designed in the Children’s Hospital Medical Center Tehran considering paraplegia patients with MMC as the case group and nonparaplegic MMC patients as a control group. Doppler ultrasound was performed to evaluate femoral artery and popliteal artery and venous properties.

Patients aged from 8 months to 12 years were evaluated. The mean diameter of the femoral arteries was 3.73 ± 0.23 and 4.72 ± 0.39 mm among paraplegic and nonparaplegic MMC patients, respectively (p = 0.02). The femoral artery flow was 0.52 ± 0.08 and 0.75 ± 0.06 L/min, respectively in the case and control groups (p = 0.015). The diameters of the femoral veins were 4.85 ± 0.34 and 5.13 ± 0.32 mm in the case and control groups, respectively (p > 0.05). Besides, the blood flows of the case and control groups’ femoral veins were 0.27 ± 0.08 and 0.14 ± 0.01 L/min, respectively (p = 0.6). It turned out that lower extremities’ arteries in the case group had significantly lower blood flow and diameter compared to those of the control group. However, the same venous properties did not show any significant differences.

The decreased arterial flow along with the unchanged venous properties leads to less stasis and better drainage of the blood, which in turn might result in a lower incidence of deep vein thrombosis 2).


Tethered cord syndrome as many as 70 % of Myelomeningocele (MM) patients have a tethered cord radiographically (some quote 10–20%), but only a minority are symptomatic. Unfortunately there is no good test to check for symptomatic retethering (SSEPs may deteriorate, 3) myelography may help)

Hydrocephalus develops in up to 80-90% of children with myelomeningocele (MM) after closure of the defect.

Traditionally, ventriculoperitoneal shunts have been used to manage hydrocephalus in these patients. A role for endoscopic third ventriculostomy (ETV) in MM has provoked much debate, principally due to anatomical variants described, which may complicate the procedure.

Perez da Rosa et al. present 7 cases of children with MM and hydrocephalus undergoing a total of 10 ETV procedures. All patients demonstrated clinical improvement (in acute/subacute cases) or stabilization (in chronic cases). Three patients requiring a second ETV have shown clinical stability and renewed radiological evidence of functioning ventriculostomies in follow-up since reintervention. ETV can be used, albeit cautiously, in selected cases of hydrocephalus associated with MM. However, the frequency with which anatomical variation is encountered and the difficulty of the assessment of success make the procedure more challenging than usual 4).

References

1)

McLone DG, Dias MS. Complications of myelomeningocele closure. Pediatr Neurosurg. 1991-1992;17(5):267-73. PubMed PMID: 1822692.
2)

Salari F, Golpayegani M, Habibi Z, Yaghoubi S, Anbarlouei M, Mehdizadeh M, Nejat F. Evaluation of Lower Extremities’ Vascular Characteristics in Myelomeningocele Patients: A Case-Control Study. Pediatr Neurosurg. 2019 Sep 5:1-5. doi: 10.1159/000502403. [Epub ahead of print] PubMed PMID: 31487737.
3)

Larson SJ, Sances A, Christenson PC. Evoked Somatosensory Potentials in Man. Arch Neurol. 1966; 15:88–93
4)

Perez da Rosa S, Millward CP, Chiappa V, Martinez de Leon M, Ibáñez Botella G, Ros López B. Endoscopic Third Ventriculostomy in Children with Myelomeningocele: A Case Series. Pediatr Neurosurg. 2015;50(3):113-8. doi: 10.1159/000381747. Epub 2015 May 27. PubMed PMID: 26021675.

Medulloblastoma outcome

Medulloblastoma outcome

All medulloblastomas are WHO grade IV.

Poor prognosticators

● younger age (especially if<3 yrs)

● disseminated (metastatic) disease

● inability to perform gross-total removal(especially if residual > 1.5cm2 in patient with localized disease)

● histological differentiation along glial, ependymal, or neuronal lines

Medulloblastoma is the most common malignant brain tumor that occurs during childhood. Multimodality treatment regimens have substantially improved survival in this disease; however, the tumour is incurable in about a third of patients with medulloblastoma, and current treatment has a detrimental effect on long-term survivors. Drugs that target cell-signaling pathways provide an alternative to conventional cytotoxic approaches to the treatment of cancer. Several pathways have been implicated in medulloblastoma formation, and knowledge of these is now being used to develop new ways of treating children with medulloblastoma 1).

Weil et al. 2) and Prados et al. 3) found female gender to be a significant favorable prognostic factor in medulloblastoma. Sex did not reveal any bearing on the outcome in the series of Kumar et al. 4).

Age, hemispheric location of the tumor, the extent of resection, and adjuvant therapy status were the important clinical prognostic factors for survival in the series of Narayan et al. 5).

Complete resection should be performed if possible as several studies have correlated outcome with the extent of resection and amount of residual tumor 6).

Gene expression profiling is highly predictive of response to therapy, predicting outcome with much greater accuracy than current staging criteria 7).

Long-term survivors of MB are at significant risk for permanent endocrinologic, cognitive, and psychological sequelae of treatments. Infants and very young children with MB remain a di cult therapeutic challenge because they have the most virulent form of the disease and are at the highest risk for treatment-related sequelae. Most common site of recurrence is p-fossa. Collins’law has also been used to define the period of the risk of recurrence (PRR) but exceptions to the law have been reported 8).


Ninety-seven samples of medulloblastoma were collected. Tumor content in samples was judged by frozen section review. Tumor ERBB2 protein and MYCC, MYCN, and TRKC mRNA levels were measured blind to clinical details using Western blotting and real-time polymerase chain reaction, respectively. Histopathologic and clinical review of each case was also performed. All data were subjected to independent statistical analysis.

Sample acquisition and analysis times ranged from 3 to 6 days. Eighty-six samples contained sufficient tumor for analysis, including 38 classic, 30 nodular desmoplastic, and 18 large-cell anaplastic (LCA) medulloblastomas. Protein and mRNA were extracted from 81 and 49 tumors, respectively. ERBB2 was detected in 40% (n=32 of 81) of tumors, most frequently in LCA disease (P=.005), and was independently associated with a poor prognosis (P=.031). A combination of clinical characteristics and ERBB2 expression provided a highly accurate means of discriminating disease risk. One hundred percent (n=26) of children with clinical average-risk, ERBB2-negative disease were alive at 5 years, with a median follow-up of 5.6 years, compared with only 54% for children with average-risk, ERBB2-positive tumors (n=13; P=.0001). TRKC, MYCC, and MYCN expression and histopathologic subtype were not associated with prognosis in this study.

Central and rapid molecular analysis of frozen medulloblastomas collected from multiple institutions is feasible. ERBB2 expression and clinical risk factors together constitute a highly accurate disease risk stratification tool 9).


The purpose of a study of was to determine the relative contributions of biological and clinical predictors of survival in patients with medulloblastoma (MB).

Clinical presentation and survival information were obtained for 119 patients who had undergone surgery for MB at the Hospital for Sick Children (Toronto, Ontario, Canada) between 1985 and 2001. A tissue microarray was constructed from the tumor samples. The arrays were assayed for immunohistochemical expression of MYC, p53, platelet-derived growth factor receptor-alpha, ErbB2, MIB-1, and TrkC and for apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling). Both univariable and multivariable analyses were conducted to characterize the association between survival and both clinical and biological markers. For the strongest predictors of survival, a weighted predictive score was calculated based on their hazard ratios (HRs). The sum of these scores was then used to give an overall prediction of survival using a nomogram.

The four strongest predictors of survival in the final multivariable model were the presence of metastatic disease at presentation (HR, 2.02; P=0.01) and p53 (HR, 2.29; P=0.02), TrkC (HR, 0.65; P=0.14), and ErbB2 (HR, 1.51; P=0.21) immunopositivity. A linear prognostic index was derived, with coefficients equal to the logarithm of these HRs. The 5-year survival rate for patients at the 10th, 50th, and 90th percentiles of the score distribution was 80.0%, 71.0%, and 35.7%, respectively, with radiation therapy and 70.5%, 58.5%, and 20.0%, respectively, without radiation therapy.

In this study, we demonstrate an approach to combining both clinical and biological markers to quantify risk in MB patients. This provides further prognostic information than can be obtained when either clinical factors or biological markers are studied separately and establishes a framework for comparing prognostic markers in future clinical studies 10).


Two rare subtypes at extreme ends of the histologic spectrum, i.e., medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas, are associated with better and worse clinical outcomes, respectively. However, there is little data about correlations between histologic features and clinical outcomes for most patients with medulloblastomas that fall between these histologic extremes of nodularity and anaplasia.

Eberhart et al. evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaplasia would presage less favorable results.

Medulloblastomas from 330 Pediatric Oncology Group patients were evaluated histologically with respect to extent of nodularity, presence of desmoplasia, grade of anaplasia, and extent of anaplasia. Pathologic and clinical data were then compared using Kaplan-Meier and log-rank analyses.

Increasing grade of anaplasia and extent of anaplasia were associated strongly with progressively worse clinical outcomes (P < 0.0001 for both). Significant anaplasia (moderate or severe) was identified in 24% of medulloblastoma specimens. Neither increasing degrees of nodularity nor desmoplasia were associated significantly with longer survival.

Moderate anaplasia and severe anaplasia were associated with aggressive clinical behavior in patients with medulloblastomas and were detected in a significant number of specimens (24%). Pathologic grading of medulloblastomas with respect to anaplasia may be of clinical utility 11).


Although surgery, radiation and high-dose chemotherapy have led to increased survival, one-third of patients succumb to their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment.

Through analysis of several well-designed multi-institutional trials, much has been learned about the clinical factors that influence outcome in children with medulloblastomas. Age younger than 3 years, bulky residual disease postoperatively, and metastasis constitute adverse prognostic features and indicate patients who are considered “high risk” for recurrence with standard therapy using 3600 cGy craniospinal radiation in conjunction with a posterior fossa dose of 5400 cGy. Patients lacking these features are considered “standard risk.”

Evaluation of biologic predictors of outcome, which may further refine treatment stratification, is in progress.

References

1)

Gilbertson RJ. Medulloblastoma: signalling a change in treatment. Lancet Oncol. 2004; 5:209–218
2)

Weil MD, Lamborn K, Edwards MS, Wara WM. Influence of a child’s sex on medulloblastoma outcome. JAMA. 1998 May 13;279(18):1474-6. PubMed PMID: 9600483.
3)

Prados MD, Warnick RE, Wara WM, Larson DA, Lamborn K, Wilson CB. Medulloblastoma in adults. Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):1145-52. PubMed PMID: 7607936.
4)

Kumar LP, Deepa SF, Moinca I, Suresh P, Naidu KV. Medulloblastoma: A common pediatric tumor: Prognostic factors and predictors of outcome. Asian J Neurosurg. 2015 Jan-Mar;10(1):50. doi: 10.4103/1793-5482.151516. PubMed PMID: 25767583; PubMed Central PMCID: PMC4352636.
5)

Narayan V, Sugur H, Jaiswal J, Arvinda HR, Arivazhagan A, Somanna S, Santosh V. Medulloblastoma: Distinctive Histo-Molecular Correlation with Clinical Profile, Radiologic Characteristics, and Surgical Outcome. Pediatr Neurosurg. 2019 Sep 3:1-12. doi: 10.1159/000501913. [Epub ahead of print] PubMed PMID: 31480064.
6)

Chatty EM, Earle KM. Medulloblastoma. A report of 201 cases with emphasis on the relationship of histologic variants to survival. Cancer. 1971 Oct;28(4):977-83. PubMed PMID: 5111749.
7)

Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002 Jan 24;415(6870):436-42. PubMed PMID: 11807556.
8)

Sure U, Berghorn WJ, Bertalan y H. Collins’ law. Prediction of recurrence or cure in childhood medulloblastoma? Clin Neurol Neurosurg. 1997; 99:113–116
9)

Gajjar A, Hernan R, Kocak M, Fuller C, Lee Y, McKinnon PJ, Wallace D, Lau C, Chintagumpala M, Ashley DM, Kellie SJ, Kun L, Gilbertson RJ. Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol. 2004 Mar 15;22(6):984-93. Epub 2004 Feb 17. PubMed PMID: 14970185.
10)

Ray A, Ho M, Ma J, Parkes RK, Mainprize TG, Ueda S, McLaughlin J, Bouffet E, Rutka JT, Hawkins CE. A clinicobiological model predicting survival in medulloblastoma. Clin Cancer Res. 2004 Nov 15;10(22):7613-20. PubMed PMID: 15569993.
11)

Eberhart CG, Kepner JL, Goldthwaite PT, Kun LE, Duffner PK, Friedman HS, Strother DR, Burger PC. Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study. Cancer. 2002 Jan 15;94(2):552-60. PubMed PMID: 11900240.
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