neurosurgery article posterior fossa tumours in children · primary intracranial tumours in...

24 > ACNR > VOLUME 13 NUMBER 4 > JULY/AUGUST 2013

T he posterior fossa is the commonest site ofprimary intracranial tumours in children. Thecommonest neoplasms are pilocytic astrocy-

toma, medulloblastoma, ependymoma and brainstem glioma. In children over one year old, over twothirds of intracranial tumours arise from the cere-bellum or brainstem, compared with 15% in adults.Survival rates of some of these lesions has improvedmarkedly over the last twenty years, due to advancesin surgical techniques, chemotherapy, delivery ofradiotherapy and, more recently, an improved under-standing of tumour biology. These tumours remainthe focus of intense research aimed not just atprolonging survival, but also at minimising theimpact of treatment on growth, cognitive develop-ment and long-term quality of life.

Clinical presentationPosterior fossa tumours often present with clinicalmanifestations of hydrocephalus and raisedintracranial pressure. More aggressive tumourspresent with a shorter history. The most prevalentsymptoms include headache, nausea andvomiting. In young children headache is reflectedin irritability and a desire not to be handled.Vomiting, usually an early morning phenomenon,may also be related to irritation of the lower fourthventricular floor, at the area postrema, by thetumour. The hyperventilation associated withvomiting often transiently improves the headache.

Raised intracranial pressure may also causedrowsiness, neck stiffness, sixth nerve palsy andvisual disturbances. Papilloedema is common inpatients presenting with long-standing progressivesymptoms. Aggressive brain stem tumours oftenpresent with pyramidal tract signs together withdisorders of ocular motility and diplopia. A headtilt may be a reflection of tonsillar herniation or afourth nerve palsy related to a diffuse brainstemtumour. Young children with progressive hydro-cephalus demonstrate macrocephaly, with fullnessof the fontanelles and increased separation ofcalvarial sutures. Ataxia arises from vermal andcerebellar hemisphere involvement, brainstemdysfunction and chronic hydrocephalus.

Headache is an uncommon complaint in earlychildhood; early referral and imaging is warranted.Similarly, early investigation of other symptomsallows rapid diagnosis and prompt initiation oftreatment.

Pilocytic astrocytomaCerebellar astrocytomas are the most frequentposterior fossa tumours in children, accounting for

up to 35% of these lesions.1 Peak age is 5 to 13 years;approximately half arise in the midline and halffrom the cerebellar hemispheres. They are circum-scribed, discrete, slow-growing lesions, often associ-ated with cysts within and around the tumour.2

On computed tomography (CT), pilocytic astro-cytomas are large cystic lesions arising from thecerebellar vermis or hemisphere. The solid compo-nents are hypodense and enhance avidly oncontrast administration. On T1-weighted magneticresonance imaging (MRI), the solid componenttends to be iso- to hypo-intense on comparisonwith grey matter; heterogeneity is due to micro-cystic and necrotic areas. It is hyperintense on T2-weighted images (Figure 1A and B). The solid andmural components enhance prominently (Figure1C). Enhancement of the cyst wall suggests tumourinfiltration of the capsule.3

Histologically these tumours are characterisedby a biphasic pattern. This consists of compactedbipolar cells with Rosenthal fibres, and loose multi-polar cells with microcysts and eosinophilic gran-ular bodies, which form globular aggregates withinastrocytic processes.2 Their slow growth permitsdevelopment of regressive changes, such ashyalinised vessels, calcification, necrosis, lympho-cytic infiltrates and cysts. In this context, necrosiscarries no prognostic significance. Rarely, pilocyticastrocytomas seed the neuraxis, although thistends to occur with hypothalamic, rather thanposterior fossa, primary tumours. In these cases theprimary tumour may still demonstrate a low prolif-eration index; such tumours generally respondwell to chemotherapy and radiotherapy, and longterm survival is still possible.4

Pilocytic astrocytomas maintain their WHOgrade I status for years; they only rarely show malig-nant transformation, and they should then betermed anaplastic pilocytic astrocytomas, ratherthan glioblastomas. Even then, their prognosis isnot uniformly poor. Reported cases had under-gone previous radiotherapy, and this was likely rele-vant to their transformation.2

A large percentage of pilocytic astrocytomas,particularly those arising within the cerebellar hemi-sphere, have demonstrated alterations in the BRAFgene, which is essential for growth signalling throughmitogen-associated protein kinase (MAPK) path-ways.5 These alterations have not been clearly asso-ciated with outcome. p16 deletions are commoner inmidbrain, brainstem and spinal cord lesions.5

Resection is the treatment of choice for well-circumscribed lesions (Figure 1D) and the factormost strongly associated with outcome is the

Posterior fossa tumoursin children – an overview of diagnosis andmanagement

N E U R O S U R G E RY A RT I C L E

Kristian Aquilinacompleted his neurosurgical trainingin Bristol in 2009. He undertook aone-year clinical fellowship inpaediatric neurosurgery at LeBonheur Children's Medical Centerand St Jude Children's ResearchHospital in Memphis, Tennessee. He issurgical lead for neuro-oncology atGreat Ormond Street Hospital. Hisother clinical and research interestsinclude the surgical management ofspasticity in cerebral palsy,particularly selective dorsalrhizotomy, and the management ofhydrocephalus.

Conflict of interest statement:The author declares that there are nofinancial or commercial conflicts ofinterest.

Correspondence address:Dr Kristian Aquilina,Department of Neurosurgery,Great Ormond Street Hospital forChildren, WC1N 3JH UK.

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extent of surgical removal.6,7 Gross total resec-tion leads to over 90% long-term survival.7

Cerebellar pilocytic astrocytomas are gener-ally resectable and adjuvant therapy is notindicated. Those arising from the brainstem,however, are often not completely resectableand require adjuvant chemotherapy, usuallyincluding carboplatin and vincristine, andconsideration of radiotherapy at progression.A clinical trial of BRAF and MAPK pathwayinhibitors, such as AZD6244, is underway.8

Another trial, using the antiangiogenic agentsbevacizumab and linalidomide, has alreadyshown some promise in Phase I and II trials.9

A recent study has reported long-term followup, to a mean of 18.4 years, for 101 childrenwith benign posterior fossa astrocytomas.6

Complete resection, confirmed radiologically,was achieved in half the patients; only three ofthese recurred. 26 of 50 residual tumoursprogressed, at a mean of 30 months; the othersdemonstrated spontaneous regression orgrowth arrest. 60% of recurrences or progres-sion occurred within two years, and only onebeyond eight years of the original surgery. Theinterval to progression was shorter for subtotalresections, solid tumours and involvement ofbrainstem or cerebellar peduncle. The authorsconclude that gross total resection should notbe aggressively pursued when the tumourinvades critical structures.

Medulloblastoma Medulloblastoma is a primitive neuroecto-dermal tumour (PNET) occurring in the cere-bellum. It is the most common malignantbrain tumour in children and represents 30%of posterior fossa tumours. It is classified asWHO grade 4 and has a propensity toleptomeningeal dissemination. The annualincidence is 6.5 per million children.10 10% ofcases are diagnosed in infancy. 75% occur inthe midline; cerebellar location is associatedwith older age and desmoplastic histology.11

Medulloblastoma is typically a midlineenhancing homogeneous posterior fossa masson CT. The mass is hypointense on T1 and T2-weighted images; it enhances heterogeneouslyon gadolinium administration. Cystic compo-nents may be present (Figure 2A and B). Thecharacteristic high cell density is reflected in


Figure 1: Pilocytic astrocytoma. T2-weighted axial (A) andpost-contrast sagittal (B) images of two posterior fossa pilo-cytic astrocytomas, demonstrating solid and cystic compo-nents; the close relationship of the tumour in (B) to thetectum (*) is evident on the axial post-contrast image in (C).Post-operative midline post-contrast MRI in (D) confirmsgross total resection of the tumour in (B) and (C).

Figure 2: Medulloblastoma. Sagittal post-contrast (A), andaxial T2 (B) images, showing typical posterior fossa medul-loblastoma. Both demonstrate heterogeneous nature of thetumour. Obstruction of the aqueduct and secondaryobstructive hydrocephalus is evident in (A); (C) demonstratesa nodular medulloblastoma in an infant with the typical‘bunch of grapes’ appearance; (D) is an intra-operativephotomicrograph obtained during resection of a posteriorfossa medulloblastoma –‘t’ represents residual tumouraround the cavity; the fourth ventricular floor ‘f’ is exposedand free of tumour; the arrow points to the dilated caudalend of the aqueduct after decompression.

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diffusion restriction. Leptomeningeal diseaseis identified as enhancing nodules on thesurface of the brain and spinal cord, oftenreferred to as ‘sugar coating’. Histologically, medulloblastoma is

composed of small blue round cells with ahigh nuclear to cytoplasmic ratio. The 2007WHO classification of central nervous systemtumours identified four distinct pathologicalsubgroups: classical (65-80%), desmoplastic /nodular (15-25%), medulloblastoma withextensive nodularity (15-25%) (Figure 2C)and an anaplastic / large cell variant (4-5%).2,12 The desmoplastic variant is charac-terised by pale nodular areas within a retic-ulin network; this is commoner in older chil-dren and is associated with a better prog-nosis. The large cell and anaplastic variantsdemonstrate abundant mitoses and markednuclear pleiomorphism; this subgroup is asso-ciated with a poor prognosis. Extensive investigation into the genetic

differences in medulloblastoma over the lastten years has led to further classification intodistinct molecular variants. Current clinicalmedulloblastoma trials are still based onhistological classification. Genetic typing

however is not far from clinical use and islikely to improve prognostication and riskstratification, as well as allow tailored thera-peutic approaches. Medulloblastomas arise from aberrant

proliferation of granule neuron precursorcells that go on to constitute the externalgranular layer of the cerebellum. The differentsignalling pathways involved in this complexprocess have led to the identification of fourmolecular subgroups.13 Wnt signalling has animportant role in neural stem cell prolifera-tion in the normal cerebellum.14 This pathway,originally identified in mutant wingless fruit-flies, is fundamental to neural tubepatterning. Tumours involving Wnt pathwayanomalies are more likely to arise in youngerchildren, demonstrate classic histology, tendto be located within the fourth ventricle andare associated with a very good prognosis;their nuclei stain positively for β catenin.13,15

The sonic hedgehog (Shh) signallingpathway regulates progenitor cell prolifera-tion in the external granular layer; medul-loblastomas associated with Shh signallingabnormalities tend to arise within the cere-bellar hemisphere and are more likely to

occur in infants or older children; their prog-nosis is intermediate.16 Abnormalities in thesepathways are not simply related to mutationsin expressed genes, but also to epigeneticchanges leading to abnormal expression oftumour suppressor genes, including promoterinactivation by DNA methylation, histonemodification and gene silencing by nonpro-tein-coding micro RNA’s.17 There are two addi-tional non-Wnt, non-Shh subtypes; both tendto be either classic or large cell / anaplastictumours, frequently with metastases at pres-entation and myc amplification. Group 3 havea poor and Group 4 an intermediate prog-nosis.13

Following resection, (Figure 2D) furtheradjuvant treatment of medulloblastomadepends on whether they are classified asstandard or high risk. Staging requires MRI ofthe brain and spine, without and withcontrast. CSF from the lumbar region is alsorequired; this is obtained two weeks post-operatively to avoid false positive cytologyearly after resection, and is more sensitivethan ventricular CSF.18 High risk patientsinclude all children under three as well asthose with positive CSF, macrometastases onMRI implying tumour dissemination and >1.5cm2 of residual tumour visible on post-contrast MRI within 24 to 72 hours of surgery.Children older than three with anaplastichistology or c-myc amplification are alsoconsidered high risk.Children over three at standard risk

undergo craniospinal irradiation (23.4 Gy),commenced within 40 days of surgery with aposterior fossa boost to a total dose of 54-55.8Gy. This is combined with weekly concurrentchemotherapy. Hyperfractionation does notlead to an improvement in overall or progres-sion free survival.19 Based on this regimen, fiveyear event-free survival is up to 80%.10

Historically the five year progression-freesurvival for children with high risk disease is40%.20 Recent studies have focused onimproving prognosis in this group usingmultimodality treatments.21 High risk patientsare treated with 36 Gy to the craniospinal axisfollowed by a posterior fossa boost to 54 to 56Gy. Studies have evaluated the use of hyper-fractionated radiotherapy, including posteriorfossa boosts to 60 Gy and myeloablativecourses of chemotherapy followed by periph-eral blood stem cell rescue, yielding five yearprogression free survival of up to 73%.15,22

The neurocognitive sequelae of radio-therapy are more severe in young children. Ininfants and children under three, repeatedcycles of chemotherapy have been used aftersurgery in an attempt to prevent progressionuntil they become eligible for radiotherapy.Outcomes from early studies were poor,encouraging the introduction of high dosechemotherapy regimens.10 It is likely that suchstudies were affected by multiple tumourbiological factors which directly affectedsurvival; infants with desmoplastic variants,for example, consistently showed betteroutcomes than all the others.23


Figure 3: (A) post-contrast MR image demonstrating an ependymoma in the cerebellopontine angle (asterisk); the tumour ishypointense and does not enhance; the brainstem is distorted and rotated to the right; (B) FLAIR image demonstrating a diffusehyper-intense lesion consistent with a pontine glioma. (C) and (D) post-contrast axial and sagittal MR images of posterior fossaATRT; the tumour is large and diffuse, involving the cerebellum and brainstem and extends superiorly through the tentorialincisura.


ACNR > VOLUME 13 NUMBER 4 > JULY/AUGUST 2013 > 27

Ependymoma Ependymoma is the third most commonpaediatric brain tumour; over 50% of casesarise in children under five years of age.24

Infratentorial ependymomas arise from thefloor or roof of the fourth ventricle and growinto the ventricular lumen. They have apropensity to extend through the foramen ofLuschka into the cerebellopontine cistern andaround the brainstem (Figure 3A), as well asdown through the foramen magnum. Theextent of surgical resection is a major determi-nant of outcome. In historical series, five-yearoverall survival for ependymoma has rangedfrom 50 to 64%.23 However institutions withgross total resection rates of up to 82% havereported five-year overall survival figures of87.3% and 62.1% for ependymomas and malig-nant ependymomas respectively.25

Infratentorial ependymomas in children areclassified as WHO grade 2 or 3, grade 1 beingreserved only for subependymoma andmyxopapillary ependymoma.2 They are well-delineated soft, heterogeneous tumours, oftenwith cystic, necrotic and haemorrhagicelements. Histologically they are characterisedby perivascular and, more rarely, ependymalrosettes. The latter consists of tumour cellsconcentrically organised around a lumen.2

Ependymomas stain positively with GFAP,NCAM and EAM. Multiple chromosomalanomalies have been identified in ependy-momas. Anomalies on chromosome 22q havebeen reported in 26 to 71% of ependymomas.26

Chromosome 1q gain has been found in up to22% of childhood ependymomas, and is asso-ciated with posterior fossa location, anaplasticfeatures and a poor prognosis.27 A recent studyidentified gains at chromosome 1q, hightumour cell density and high mitotic count asdefining features of a high risk subgroup ininfratentorial ependymoma.27

On CT, ependymomas are iso- or hyper-dense lesions. Punctate calcification isdetectable in up to 50% of cases. Theyenhance heterogeneously on contrast admin-istration.3 On MRI, they are iso- to hypo-intenseon T1-weighted sequences and hypointenseon T2. Calcification, cysts, areas of necrosis andmicro-haemorrhages cause heterogeneitywithin the tumour mass on enhanced andnon-enhanced sequences. Leptomeningealdissemination at presentation is less commonthan in medulloblastoma; full spinal MRI atdiagnosis is imperative as part of the stagingprocess.28

Despite several multi-institutional studies,mostly including platinum-based agents, nosingle chemotherapeutic regimen has demon-strated significant survival benefit for ependy-moma.29,30 The role of chemotherapy alongsidepost-operative radiotherapy remains unclear.In a recent single-institution study, conformalradiotherapy, administered immediately aftersurgery, led to better overall survival rates, up to85% at five years, compared to earlier studieswith up to 73% at five years.25 This may bepartly attributable to the high rate of gross totalresection in this study. Radiotherapy was

confined to the tumour bed and a 10mmmargin, and was also administered, for the firsttime, to children under three years; childrenunder 18 months received 54 Gy rather thanthe standard dose of 59.4 Gy. The seven-yearlocal control rate was 87%. Among thepatients with differentiated ependymomatreated with gross total resection and 59.4 Gy,there were very few local failures. The lowfrequency of side effects from limited volumeirradiation has also encouraged this group torecommend repeated surgery and re-irradia-tion for children presenting with local recur-rence.31

Brainstem tumoursBrainstem gliomas account for 10 to 20% of allCNS tumours in children.32 They are broadlyclassified into diffuse or focal. Focal brainstemtumours are well-circumscribed masses thatmay be intrinsic, exophytic or cervi-comedullary.33,34 Diffuse intrinsic pontinegliomas are high grade fibrillary astrocytomaswith median overall and progression-freesurvival of up to eleven and nine monthsrespectively (Figure 3B).35 They present with ashort history, often characterised by cranialnerve palsies and ataxia. Hydrocephalusoccurs late. They are diagnosed radiologicallyand when typical, do not require biopsy. Theyare hyperintense on T2- and hypointense onT1-weighted images, with ill-defined bound-aries and diffuse enlargement of the brain-stem. They generally do not enhance withcontrast. Surgical resection has no role inthese tumours. Despite several clinical trialsover the last fifteen years, based on variouschemotherapeutic agents and radiotherapydelivery techniques, there has been noimprovement in clinical outcome. Focal gliomas are discrete solid or cystic

tumours, under 2cm in diameter, and arecommonly low grade astrocytomas. In a recentlarge retrospective study of focal brainstemgliomas, following 52 children over a mean often years, the survival rate was 98% at five yearsand 90% at ten years; 36. 5% underwent gross ornear total resection. The authors recommendthat surgery should be pursued if the tumour isconsidered accessible and the family under-stand the risks of new neurological deficit. Inother situations, the authors recommend stereo-tactic biopsy, followed by radiation for clinicalor image-based progression.36

Atypical teratoid rhabdoid tumour(ATRT)ATRT is a malignant WHO grade IV tumourwith a poor prognosis, occurring typically inchildren under two years of age.Approximately 15% of children under 36months with a malignant brain tumour havean ATRT.37 First described in 1987, it is histolog-ically difficult to differentiate from medul-loblastoma or PNET. About half arise in theposterior fossa. Due to their high growth, pres-entation is often rapid, with macrocephaly andprogressive neurological deficit. Up to 20%present with disseminated disease.38

Radiologically, posterior fossa ATRT’s ofteninvade the cerebellopontine angle andenhance brightly on contrast administration.They are hyperdense on CT, with ill-definedwispy margins. On MRI, the tumour is heteroge-nous due to areas of haemorrhage, necrosisand cyst formation (Figure 3C and D). Histologically, ATRT consists of sheets of

rhabdoid cells within a background of epithe-lial, mesenchymal or neuroectodermal cells.2

Mitotic labelling typically shows indices of 50to 100%. These tumours characteristicallydemonstrate mutation or inactivation of theINI1 gene on chromosome 22q 11.2. This isalso abnormal in rhabdoid tumours outsidethe central nervous system, including the renaland extra-renal forms. Although the exact func-tion of this gene is unknown, it is a componentof an ATP-dependent chromatin remodellingcomplex and is involved in the regulation oftranscription. The presence of an INI1 muta-tion in a tumour resembling PNET, evenwithout sheets of rhabdoid cells, is still suffi-cient to secure the diagnosis of ATRT.39

Treatment of ATRT consists of combinationsof surgery, multi-agent chemotherapy andradiotherapy. Median overall survival for alarge cohort was 17.3 months.40 Patients withgross total resection had longer survival thansubtotal resection or biopsy. Survival for chil-dren under three years old who also hadradiotherapy was 15.8 months, compared to7.9 months for those who did not. Variability inchemotherapy regimens, in conjunction withthe small numbers of children, has made itdifficult to establish the comparative efficacyof different agents. Intrathecal chemotherapyhas been shown to be of benefit in somepatients.40 l

1. Davis FG, McCarthy BJ. Epidemiology of brain tumors.Curr Opin Neurol 2000;13:635-640.

2. Louis D.N. OH, Wiestler OD, Cevenee WK. WHO classi-fication of tumours of the central nervous system. Lyon:International Agency for Research on Cancer (IARC),2007.

3. Poretti A, Meoded A, Huisman TA. Neuroimaging ofpediatric posterior fossa tumors including review of theliterature. J Magn Reson Imaging 2012;35:32-47.

4. Gajjar A, Bhargava R, Jenkins JJ, Heideman R, SanfordRA, Langston JW, et al. Low-grade astrocytoma withneuraxis dissemination at diagnosis. J Neurosurg1995;83:67-71.

5. Horbinski C, Hamilton RL, Nikiforov Y, Pollack IF.Association of molecular alterations, including BRAF,with biology and outcome in pilocytic astrocytomas.Acta Neuropathol 2010;119:641-9.

6. Ogiwara H, Bowman RM, Tomita T. Long-term follow-upof pediatric benign cerebellar astrocytomas. Neurosurgery70:40-47; discussion 47-48, 2012.

7. Wisoff JH, Sanford RA, Heier LA, Sposto R, Burger PC,Yates AJ, et al. Primary neurosurgery for pediatric low-grade gliomas: a prospective multi-institutional studyfrom the Children's Oncology Group. Neurosurgery68:1548-1554; discussion 1554-1545, 2011.

8. Pollack IF. Multidisciplinary management of childhoodbrain tumors: a review of outcomes, recent advances, andchallenges. J Neurosurg Pediatr 2011;8:135-48.

9. Warren KE, Goldman S, Pollack IF, Fangusaro J,Schaiquevich P, Stewart CF, et al. Phase I trial oflenalidomide in pediatric patients with recurrent, refrac-tory, or progressive primary CNS tumors: Pediatric BrainTumor Consortium study PBTC-018. J Clin Oncol2011;29:324-9.


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11. Dhall G. Medulloblastoma. J Child Neurol2009;24:1418-30.

12. Polkinghorn WR, Tarbell NJ. Medulloblastoma: tumorige-nesis, current clinical paradigm, and efforts to improverisk stratification. Nat Clin Pract Oncol 2007;4:295-304.

13. Taylor MD, Northcott PA, Korshunov A, Remke M, ChoYJ, Clifford SC, et al. Molecular subgroups of medul-loblastoma: the current consensus. Acta Neuropathol2012;123:465-72.

14. Ciani L, Salinas PC. WNTs in the vertebrate nervoussystem: from patterning to neuronal connectivity. Nat RevNeurosci 2005;6:351-62.

15. Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE,Merchant TE, et al. Risk-adapted craniospinal radio-therapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblas-toma (St Jude Medulloblastoma-96): long-term resultsfrom a prospective, multicentre trial. Lancet Oncol2006;7:813-20.

16. Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS,Eden C, et al. Subtypes of medulloblastoma have distinctdevelopmental origins. Nature 2010;468:1095-9.

17. Faria CM, Rutka JT, Smith C, Kongkham P. Epigeneticmechanisms regulating neural development and pediatricbrain tumor formation. J Neurosurg Pediatr 2011;8:119-32.

18. Gajjar A, Fouladi M, Walter AW, Thompson SJ, ReardonDA, Merchant TE, et al. Comparison of lumbar andshunt cerebrospinal fluid specimens for cytologic detectionof leptomeningeal disease in pediatric patients with braintumors. J Clin Oncol 1999;17:1825-8.

19. Lannering B, Rutkowski S, Doz F, Pizer B, Gustafsson G,Navajas A, et al. Hyperfractionated versus conventionalradiotherapy followed by chemotherapy in standard-riskmedulloblastoma: results from the randomized multi-center HIT-SIOP PNET 4 trial. J Clin Oncol2012;30:3187-93.

20. Packer RJ, Rood BR, MacDonald TJ. Medulloblastoma:present concepts of stratification into risk groups. PediatrNeurosurg 2003;39:60-7.

21. Bartlett F, Kortmann R, Saran F. Medulloblastoma. ClinOncol (R Coll Radiol) 2013;25:36-45.

22. Gandola L, Massimino M, Cefalo G, Solero C, SpreaficoF, Pecori E, et al. Hyperfractionated accelerated radio-therapy in the Milan strategy for metastatic medulloblas-toma. J Clin Oncol 2009;27:566-71.

23. Rutkowski S, Gerber NU, von Hoff K, Gnekow A, BodeU, Graf N, et al. Treatment of early childhood medul-loblastoma by postoperative chemotherapy and deferredradiotherapy. Neuro Oncol 2009;11:201-10.

24. Duffner PK, Krischer JP, Sanford RA, Horowitz ME,Burger PC, Cohen ME, et al. Prognostic factors in infantsand very young children with intracranial ependymomas.Pediatr Neurosurg 1998;28:215-22.

25. Merchant TE, Li C, Xiong X, Kun LE, Boop FA, SanfordRA. Conformal radiotherapy after surgery for paediatricependymoma: a prospective study. Lancet Oncol2009;10:258-66.

26. Mack SC, Taylor MD. The genetic and epigenetic basis ofependymoma. Childs Nerv Syst 2009;25:1195-201.

27. Godfraind C, Kaczmarska JM, Kocak M, Dalton J,Wright KD, Sanford RA, et al. Distinct disease-riskgroups in pediatric supratentorial and posterior fossaependymomas. Acta Neuropathol 2012;124:247-57.

28. Yuh EL, Barkovich AJ, Gupta N. Imaging of ependy-momas: MRI and CT. Childs Nerv Syst 2009;25:1203-13.

29. Brandes AA, Cavallo G, Reni M, Tosoni A, Nicolardi L,Scopece L, et al. A multicenter retrospective study ofchemotherapy for recurrent intracranial ependymaltumors in adults by the Gruppo Italiano Cooperativo diNeuro-Oncologia. Cancer 2005;104:143-8.

30. Geyer JR, Sposto R, Jennings M, Boyett JM, Axtell RA,Breiger D, et al. Multiagent chemotherapy and deferredradiotherapy in infants with malignant brain tumors: areport from the Children's Cancer Group. J Clin Oncol2005;23:7621-31.

31. Merchant TE, Boop FA, Kun LE, Sanford RA. A retrospec-tive study of surgery and reirradiation for recurrentependymoma. Int J Radiat Oncol Biol Phys 2008;71:87-97.

32. Recinos PF, Sciubba DM, Jallo GI. Brainstem tumors:where are we today? Pediatr Neurosurg 2007;43:192-201.

33. Epstein F ME. Intrinsic brainstem tumors of childhood:surgical indications. J Neurosurg 1986;64:11-15.

34. Sandri A, Sardi N, Genitori L, Giordano F, Peretta P,Basso ME, et al. Diffuse and focal brain stem tumors inchildhood: prognostic factors and surgical outcome.Experience in a single institution. Childs Nerv Syst2006;22:1127-35.

35. Hargrave D, Bartels U, Bouffet E. Diffuse brainstemglioma in children: critical review of clinical trials. LancetOncol 2006;7:241-8.

36. Klimo P Jr, Pai Panandiker AS, Thompson CJ, Boop FA,Qaddoumi I, Gajjar A, et al. Management and outcomeof focal low-grade brainstem tumors in pediatric patients:the St. Jude experience. J Neurosurg Pediatr, 2013.

37. Reddy AT. Atypical teratoid/rhabdoid tumors of thecentral nervous system. J Neurooncol 2005;75:309-13.

38. Hilden JM, Meerbaum S, Burger P, Finlay J, Janss A,Scheithauer BW, et al. Central nervous system atypicalteratoid/rhabdoid tumor: results of therapy in childrenenrolled in a registry. J Clin Oncol 2004;22:2877-84.

39. Biegel JA, Kalpana G, Knudsen ES, Packer RJ, RobertsCW, Thiele CJ, et al. The role of INI1 and the SWI/SNFcomplex in the development of rhabdoid tumors: meetingsummary from the workshop on childhood atypical tera-toid/rhabdoid tumors. Cancer Res 2002;62:323-8.

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NEUROSURGERY ART IC L E

BOOK REV I EWS

If it is the case that “Medicine is fundamentally narrative”,as suggested by Kathleen Montgomery Hunter in Doctors’Stories. The narrative structure of medical knowledge(Princeton University Press, 1991:5), then the kinship ofmedical practice with the verbal and visual narrativesencountered respectively in literature and art is obvious.In focusing on brain disease as portrayed in novels,theatre, and film, the editors of this volume have at theirdisposal a potentially limitless resource for discussion (onoccasion addressed in the pages of ACNR).Many of the usual suspects are summoned to this

banquet of literature/art and medicine: van Gogh (specif-ically his letters, replete with references to literature),Dostoevsky (accounts of epilepsy), Chekhov (doctors),Charcot (his interest in the theatre), Proust (diseases anddoctors), and Balzac (doctors, and a possible earlyaccount of schizophrenia in the character of LouisLambert), as well as less familiar names such as BlaiseCendrars and Joseph Gerard. The two most substantial chapters, both authored by

Sebastian Dieguez, undertake in-depth surveys of doublesand of amnesia. With respect to doubles, an extendedreview of literary contributions leads to the argument thatcognitive mechanisms may underpin both clinical andscientific research and literary creations. With respect to

amnesia, criticisms of literary amnesiacs as too often ofretrograde autobiographical type, rare in clinical practice,are rejected through citation of “stranger-than-fiction” typecases in the medical literature, and Dieguez contends thatintuitive conceptions of memory may feed in to scientificunderstanding and vice versa, a notion which may be atodds with principles of neuropsychological research.David Perkin gives examples of movement disorders he

has encountered in his reading for pleasure, includingsome pretty convincing accounts of hemifacial spasm,tremor, and dystonia, but he reports (191) only oneexample which might fulfil the criteria of Tourette’ssyndrome. One hesitates to contradict so eminent aneurologist and so avid a reader, but I would recommendhim to ponder some possible examples cited in ACNR2003;3(5):26-27, and would be interested to hear histhoughts on the character of Pozdnyshev in Leo Tolstoy’s1889 novella The Kreutzer Sonata.As with previous volumes in this series, the book’s

expense is made acceptable by the high production values,with only occasional errors (e.g p. 161, Primo Levi’s If this isa man is given as published in 1942, when the writer had yetto be incarcerated, rather than 1947, the date of the firstItalian edition). We may anticipate further volumesdevoted to these kindred, narrative-based, subjects. l

Literary Medicine: Brain Disease and Doctors inNovels, Theater, and Film(Frontiers of Neurology and Neuroscience volume 31)

Editors: Bogousslavsky J, Dieguez S Published by: Karger, 2013Price: €103.00 ISBN: 9783318022711

Reviewed by: AJ Larner, Cognitive Function Clinic, WCNN, Liverpool, UK.


neurosurgery article posterior fossa tumours in children · primary intracranial tumours in...

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