UpToDate: Pediatric intracranial tumor

Pediatric intracranial tumor

Epidemiology

Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood.

The location of brain tumors in very young children differs from the posterior fossa predominance of older children. This is especially true in the first 6– 12 months of life, where supratentorial location is signicantly more common.

Approximately 20% of pediatric intracranial tumors arise from the thalamus or brainstem, with an incidence rate of 5% and 15%, respectively.

Medulloblastoma is the most common malignant pediatric intracranial tumor.

Diffuse intrinsic pontine glioma account for 10% to 25% of pediatric intracranial tumor.

Diagnosis

Bächli et al., from the Heidelberg University Hospital, Germany, report a single-institutional collection of pediatric brain tumor cases that underwent a refinement or a change of diagnosis after completion of molecular diagnostics that affected clinical decision-making including the application of molecularly informed targeted therapies. 13 pediatric central nervous system tumors were analyzed by conventional histology, immunohistochemistry, and molecular diagnostics including DNA methylation profiling in 12 cases, DNA sequencing in 8 cases and RNA sequencing in 3 cases. 3 tumors had a refinement of diagnosis upon molecular testing, and 6 tumors underwent a change of diagnosis. Targeted therapy was initiated in 5 cases. An underlying cancer predisposition syndrome was detected in 5 cases. Although this case series, retrospectiveand not population based, has its limitations, insight can be gained regarding precision of diagnosis and clinical management of the patients in selected cases. Accuracy of diagnosis was improved in the cases presented here by the addition of molecular diagnostics, impacting clinical management of affected patients, both in the first-line as well as in the follow-up setting. This additional information may support the clinical decision making in the treatment of challenging pediatric CNS tumors. Prospective testing of the clinical value of molecular diagnostics is currently underway 1).

Treatment

Malignant brain tumors represent a true therapeutic challenge in neurooncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group.

The pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications.

At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors.

Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors.

Different approaches have been explored: * Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG (Pediatric Oncology Group). * Postoperative chemotherapy without irradiation in the SFOP (Société Française d’Oncologie Pédiatrique) and in the GPO (German Pediatric Oncology) studies. *

The role of high-dose chemotherapy with autologous stem cells transplantation was explored in different ways: High-dose chemotherapy given in all patients as proposed in the Head Start protocol. High-dose chemotherapy given in relapsing patients as salvage treatment in the French strategy. In the earliest trials, the same therapy was applied to all histological types of malignant brain tumors and whatever the initial extension of the disease. This attitude was justified by the complexity of the classification of all brain tumors that has evolved over the past few decades leading to discrepancy between the diagnosis of different pathologists for a same tumor specimen. Furthermore, it has become increasingly obvious that the biology of brain tumors in very young children is different from that seen in older children. However, in the analysis of these trials an effort was made to give the results for each histological groups, according to the WHO classification and after a central review of the tumor specimens. All these collected data have brought to an increased knowledge of infantile malignant brain tumors in terms of diagnosis, prognostic factors and response to chemotherapy. Furthermore a large effort was made to study long term side effects as endocrinopathies, cognitive deficits, cosmetic alterations and finally quality of life in long term survivors. Prospective study of sequelae can bring information on the impact of the different factors as hydrocephalus, location of the tumor, surgical complications, chemotherapy toxicity and irradiation modalities. With these informations it is now possible to design therapeutic trials devoted to each histological types, adapted to pronostic factors and more accurate treatment to decrease long term sequelae 2).

Complications

Case series

1)

Bächli H, Ecker J, van Tilburg C, Sturm D, Selt F, Sahm F, Koelsche C, Grund K, Sutter C, Pietsch T, Witt H, Herold-Mende C, von Deimling A, Jones D, Pfister S, Witt O, Milde T. Molecular Diagnostics in Pediatric Brain Tumors: Impact on Diagnosis and Clinical Decision-Making – A Selected Case Series. Klin Padiatr. 2018 Jul 11. doi: 10.1055/a-0637-9653. [Epub ahead of print] PubMed PMID: 29996150.
2)

Kalifa C, Grill J. The therapy of infantile malignant brain tumors: current status? J Neurooncol. 2005 Dec;75(3):279-85. Review. PubMed PMID: 16195802.

UpToDate: Edinburgh visual gait score

Edinburgh visual gait score

Complex gait test analysis systems are not generally available worldwide, and no simple system of assessing gait by observation has been validated specifically for use in patients with cerebral palsy.

Read et al., developed a visual gait analysis score for use in cerebral palsy. Videotaped sequences of patients were recorded before and after surgery as part of a three-dimensional gait study using a Vicon (Oxford, U.K.) gait analysis system. The score demonstrated good intraobserver and interobserver reliability. The numeric values of the score elements correlated well with the measurements obtained from instrumented gait analysis for the same patients, and the score was able to detect postoperative change 1).


EVGS can be a supportive tool that adds quantitative data instead of only qualitative assessment to a video only gait evaluation 2).


Robinson et al., propose an MCID value of 2.4 for the EVGS; representing the improvement in gait score after surgery that is likely to reflect a clinical improvement in function. This MCID is closely related to other studies defining post-operative improvements in kinematic data (GPS) and may offer guidance to post-surgical changes that might reasonably be expected to either improve or prevent deteriorating function 3).


36 children (age 4-13 y) with spastic diplegia (gross motor classification system level I (n=14), II (n=15) and III (n=7) were included retrospectively from the database of the VU University Medical Center Amsterdam. Children underwent Selective dorsal rhizotomy for spastic diplegia (SDR) between January 1999 and May 2011. Patients were included if they received clinical gait analysis before and five years post-SDR, age >4 years at time of SDR and if brain MRI-scan was available.

Overall gait quality was assessed with Edinburgh visual gait score (EVGS), before and five years after SDR. In addition, knee and ankle angles at initial contact and midstance were evaluated. To identify predictors for gait improvement, several factors were evaluated including: functional mobility level (GMFCS), presence of white matter abnormalities on brain-MRI, and selective motor control during gait (synergy analysis).

Overall gait quality improved after SDR, with a large variation between patients. Multiple linear regression analysis revealed that worse score on EVGS and better GMFCS were independently related to gait improvement. Gait improved more in children with GMFCS I & II compared to III. No differences were observed between children with or without white matter abnormalities on brain MRI. Selective motor control during gait was predictive for improvement of knee angle at initial contact and midstance, but not for EVGS.

Functional mobility level and baseline gait quality are both important factors to predict gait outcomes after SDR. If candidates are well selected, SDR can be a successful intervention to improve gait both in children with brain MRI abnormalities as well as other causes of spastic diplegia 4).

1)

Read HS, Hazlewood ME, Hillman SJ, Prescott RJ, Robb JE. Edinburgh visual gait score for use in cerebral palsy. J Pediatr Orthop. 2003 May-Jun;23(3):296-301. PubMed PMID: 12724590.
2)

Del Pilar Duque Orozco M, Abousamra O, Church C, Lennon N, Henley J, Rogers KJ, Sees JP, Connor J, Miller F. Reliability and validity of Edinburgh visual gait score as an evaluation tool for children with cerebral palsy. Gait Posture. 2016 Sep;49:14-18. doi: 10.1016/j.gaitpost.2016.06.017. Epub 2016 Jun 15. PubMed PMID: 27344448.
3)

Robinson LW, Clement ND, Herman J, Gaston MS. The Edinburgh visual gait score – The minimal clinically important difference. Gait Posture. 2017 Mar;53:25-28. doi: 10.1016/j.gaitpost.2016.12.030. Epub 2017 Jan 3. PubMed PMID: 28073083.
4)

Oudenhoven LM, van der Krogt MM, Romei M, van Schie PEM, van de Pol LA, van Ouwerkerk WJR, Harlaar Prof J, Buizer AI. Factors associated with long-term improvement of gait after selective dorsal rhizotomy. Arch Phys Med Rehabil. 2018 Jul 4. pii: S0003-9993(18)30442-8. doi: 10.1016/j.apmr.2018.06.016. [Epub ahead of print] PubMed PMID: 29981315.

Update: Intramedullary spinal cord abscess

Intramedullary spinal cord abscess

Intramedullary spinal cord abscess due to congenital dermal sinus (CDS) is rare and often co-exists with an inclusion tumor such as dermoid/epidermoid cyst.

CDS are the commonest cause of intramedullary spinal cord abscess (IMSCA) 1).

Prasad et al. did a literature review to analyze all cases of pediatric IMSCA secondary to CDS by searching online databases starting from the oldest case reported.

Only 50 cases have been reported and were analyzed. Mean age was 22.6 months (range 1 month-15 years). Fever, acute flaccid lower limbweakness, and urinary disturbances were the most common presenting features. Dermal sinus was commonest in lumbosacral region. Inclusion cysts were observed in 50% of cases. Staphylococcus aureus was the most the common organism. Mean follow-up duration was 18.2 months (range 1 week-156 months). Majority of the cases underwent multilevel laminectomy with myelotomy and drainage of abscess. Outcome was good-to-excellent in around 60% cases with four deaths. Presence of fever and limb weakness was significantly associated with poor outcomes.

Intramedullary abscess secondary to CDS is very rare. Complete sinus tract excision, myelotomy and drainage of abscess, and decompression of co-existent inclusion cysts with prolonged antibiotic therapy remain the standard treatment. Approximately 60% cases achieve good outcomes. Fever and limb weakness portend poorer outcomes than those without 2).

1)

Kanaheswari Y, Lai C, Raja Lope RJ, Azizi AB, Zulfiqar MA. Intramedullary spinal cord abscess: The result of a missed congenital dermal sinus. J Paediatr Child Health. 2014 Aug 7. doi: 10.1111/jpc.12707. [Epub ahead of print] PubMed PMID: 25099316.

2)

Prasad GL, Hegde A, Divya S. Spinal Intramedullary Abscess Secondary to Dermal Sinus in Children. Eur J Pediatr Surg. 2018 Jun 1. doi: 10.1055/s-0038-1655736. [Epub ahead of print] PubMed PMID: 29857348.
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