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Posterior Fossa and Brainstem Tumors in Children Shikher Shrestha NINAS

Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

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Page 1: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Posterior Fossa and Brainstem Tumors in Children

Shikher ShresthaNINAS

Page 2: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Introduction..

Pediatric brain tumors – leading cause of solid cancer related death in children

~60% of tumors are in infratentorial compartment

Prognosis ranges from excellent to dismal depending on histopathological findings, extent of surgical resection and use of adjunctive therapies

Page 3: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal
Page 4: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Clinical Presentation

Depends on location and aggressiveness of the lesion

Most common presenting sign – hydrocephalus and symptoms of raised ICP

Focal compression of brainstem – cranial n. deficits and long tract signs

Compression of cerebellum – truncal ataxia and unsteady gait

If leptomeningeal spread – signs and symptoms related to the site of metastasis

Supratentorial spread – seizure and communicating hydrocephalusSpinal spread – symptoms of cord or nerve compression

Page 5: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

General Diagnostic imaging features..

MRI both brain and spinal cord to rule out leptomeningeal spread

CSF to look for malignant cells if no contraindication to LP10-14 days should be waited after surgery, if metastatic CSF work up not done preoperatively to rule out false positive result

MRI with DWI and MRS is done to distinguish various tumor subtypes or distinguish relapse from radiation necrosis

Taurine in MRS is seen in medulloblastoma

DWI measures microscopic diffusion of water in tissues. Highly cellular tumors like medulloblastoma have restricted diffusion lower signals on ADC map

Page 6: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Pilocytic Astrocytoma

Most common pediatric cerebellar tumor

Mean age 7-8 yrs

No gender predilection

WHO grade I – slow growth, indolent behavior, high survival rate

Can occur anywhere in the neuraxis, but the cerebellar hemispheres (~50%), optic pathways, thalamus, and hypothalamus are the most common sites

Page 7: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Imaging..

Well circumscribed cystic lesion with a solid enhancing nodule

CT scan:

well demarcated lesion with cyst like featuresvery occasional calcificationintense enhancement of the solid component

with contrast administration

Page 8: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

4 imaging patterns found:

enhancing mural nodule or mass with non enhancing cyst

enhancing mural nodule with intensely enhancing cyst

predominantly solid mass with no cyst component

necrotic mass with central non enhancing zone

Page 9: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Typically arise from vermis and cerebellar hemisphere

Can extend into the ventricular system

MRI

hypointense on T1 and hyperintense on T2

may be combined with DWI and MRS to differentiate with less accuracy among medulloblastomas and ependymomas

Page 10: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal
Page 11: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Leptomeningeal spread is rare but can occur if:

arising from hypothalamus

partially resected

in very young

Page 12: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Histology..

Classic biphasic pattern – loose glial tissue and compact piloid tissue

Loose glial component – protoplasmic astrocytes with eosinophilic granular bodies

Piloid component – dense sheets of bipolar cells with fibrillary process containing Rosenthal fibers

Macroscopically – well circumscribedMicroscopically – 64% show infiltration of the surrounding brain, making surgical extirpation difficult

Page 13: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Degree of mitotic index, cellular atypia and microvascular proliferation has no effect on event free survival

Histopathological evidence of vascular hyalinization, calcification, necrosis or oligodendroglioma-like features may predict a poorer clinical outcome

Very rarely, pilocytic astrocytoma undergo malignant transformation to anaplastic pilocytic astrocytoma usually after radiotherapy

Page 14: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Rarely associated with NF1 unlike supratentorial or brainstem astrocytoma

Genetics – gains at 7q34 resulting in discovery of two important fusion proteins: KIA1546-BRAF and SRGAP3-RAF1 activation of ERK/MAP pathway

Page 15: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Management

GTR – curative

Resection of mural nodule – is the KEY

Debate regarding need of removal of the cystic wall (no statistical difference)

Post op MRI to evaluate the degree of resection

GTR – 10 year survival rates >90%

Spontaneous regression after partial resection has been noted

No adjuvant therapy unless leptomeningeal spread, in which case chemo or radiotherapy given (no standard protocol exists)

Page 16: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Medulloblastoma

Most common malignant solid neoplasm of childhood

Related to PNETs (Primitive Neuro Ectodermal Tumors)

Occurs exclusively in posterior fossa

Median age 9 years in entire population and 7.3 yrs in pediatric population

Slight male predominance 1.6:1

Page 17: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Histology and Genetics

Grade IV WHO lesion

Five subtypes:

classic

desmoplastic/nodular

medulloblastoma with extreme nodularity

anaplastic

large cell

Page 18: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Desmoplastic/nodular – more favorable prognosis than large cell and anaplastic variant

Classic medulloblastoma

small blue cell tumor

densely packed undifferentiated oval cells with hyperchromatic nuclei

marked nuclear pleomorphism and brisk mitotic activity

HOMER WRIGHT ROSETTES – neoplastic cells concentrically arranged around fibrillary processes

Page 19: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Desmoplastic

“pale islands” of reticulin fibers surrounding a nodular reticulin free zone

Large cell/ Anaplastic

large nuclei with prominent nucleoli

lower nuclear/cytoplasmic ratio

Page 20: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Genetics:

Familial syndromes associated in small number of cases Gorlin’s syndrome (mutation in PTCH gene in sonic hedgehog signaling pathway)Turcot’s syndrome (APC gene mutation)Li-Fraumeni syndrome (mutation in p53 tumor

supressor)

Cell of origin – elusive

External granule layer of developing cerebellum or

Subventricular progenitor zone

Page 21: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Recent genetic subgroup analysis classification

Group A – defects in WNT signaling pathwaybehaves like classic

medulloblastoma

Group B – defects in SHH signaling extremes of age (infant or adult)desmoplastic phenotype with more

favorable outcome

Group C – poor prognosis and disseminated disease

Group D – poor prognosis and disseminated disease

N.B> Immunohistochemistry has ability to predict genetic subgroup

Page 22: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal
Page 23: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Imaging..Typically midline cerebellar lesion arising from vermis

Older children and adults – can arise from cerebellar hemisphere

CT:hyperdense lesion in cerebellar vermissurrounding vasogenic edemacalcification (22%); cyst formation (59%)

MRI:iso/hypointense to white matter in T1 and hyperintense in T2homogenous or heterogenous tumor enhancement14% have foraminal extension33% - leptomeningeal seedingseeding in spinal canal (most common) or supratentorial seedingNodular or diffuse enhancement along the leptomeninges, spinal

nerve roots or cranial nerves in case of CSF seeding

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Page 25: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

15-60% patients with evidence of mets by MRI have positive CSF cytology

70% patients with positive CSF cytology have evidence of mets in MRI

Rare sites of spread – bone, lymph nodes, liver and lung

Page 26: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal
Page 27: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Management..

Combined Surgery + Radiation + High dose chemotherapy

5 yr PFS – 80%

Risk stratification – based on age (less than 3 years), presence of disseminated disease and extent of surgical resection

Pitfall – fails to address tumor biology and system based on molecular markers and genetic subgroup analysis

Favorable markers: nuclear betacatenin and TrkC expression

Unfavorable markers: Myc genes and ERBB2

Page 28: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Chang M Staging..

Page 29: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Surgery for Medulloblastoma

Goal – complete resection without causing neurological injuries

Post operative imaging within 24 to 48 hrs

If >1.5 cm2 residual tumor – repeat procedure – if safe and anatomically feasible

Page 30: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Treatment of Children >3yrs with average risk medulloblastoma

Radiosensitive; hence radiotherapy incorporated for age > 3yrs

Dose: 23.4 Gy with posterior fossa boost of 54 Gy, followed by 12 months of chemotherapy

Page 31: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Treatment of Children > 3yrs with High risk medulloblastoma

5 year event free survival – 30-70%

Surgery + craniospinal radiation with 36 to 39.6 Gy

with posterior fossa boost followed by intense

cyclophosphamide, vincristine, cisplatin and peripheral

stem cell rescue

Page 32: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Treatment of Infants and Young Children with medulloblastoma

Developing brain susceptible to the toxicity of treatment regime

Severe neurocognitive decline secondary to craniospinal irradiation

Use of chemotherapeutic strategies to delay or avoid craniospinal radiation until the child reaches 3 years

Overall 5 yrs PFS rate 31.8% but increased to 69% if GTR

Chemotherapy used - cisplatin, vincristine, etoposide and cyclophosphamide

Methotrexate addded for disseminated disease

Page 33: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Salvage strategies

After relapse of medulloblastoma

Myeloablative chemotherapy with autologous stem cell rescue

Intrathecal chemotherapy

Page 34: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Novel therapeutics

Sonic hedgehog (SHH) pathway inhibitor – GDC-0449

Proton Beam therapyutilizes charged beams that have finite range in tissues spares normal tissues compared to conventional

radiotherapyPhase II trial

Intrathecal (IT) chemotherapydelayes radiation therapysalvage recurrent diseasetreat leptomeningeal seedingsuccessfully used to avoid craniospinal radiation in

Pediatric leukemia population

Page 35: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Ependymoma..

Third most frequent brain tumor

1926, Cushing and Bailey 6.4% of primary brain tumors in children (0-14 yrs)30% of tumors in children less than 3 years of age

Mean age of presentation: 3.7 yrs

5 years survival rates: 60%

Can occur throughout the neuraxis

Posterior fossa (fourth ventricle, CPA) more common location (70%)

Page 36: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Imaging

Fills the 4th ventricle

Extends laterally through the foramina of Luschka (15%) and inferiorly through Magendie (60%)

MRI: low T1, high T2 and intermediate to high FLAIR signal intensity

Heterogenous due to calcifications (50%), cystic areas and hemorrhage

Heterogenous enhancement

DWI – intermediate between pilocytic (low) and PNETs (high)

Page 37: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal
Page 38: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Often encase neurovascular structures in the CPA, making surgical removal difficult

Ikezaki et al. classification

1. Lateral type – presenting in CPA – poor prognosis secondary to involvement of cranial nerves and brainstem

2. Localized to 4th ventricle floor – intermediate prognosis3. Localized to roof of 4th ventricle – most favorable outcome

Leptomeningeal spread – 8-12% - more frequently with anaplastic grades

Leptomeningeal disease with drop metastasis – most common in lumbosacral region

Page 39: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Histology..

WHO – three grades and 4 histological variants

Page 40: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Classical histological features:

Perivascular and ependymal rosettesPerivascular : Ependymal cell processes radially

arranged around a cell-free perivascular zoneEpendymal: tumor cells concentrically arranged to

form lumen

Anaplastic:

1. brisk mitotic activity2. Increased cellularity3. Microvascular proliferation4. Pseudopallisading necrosis

Page 41: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Genetics:

most common genetic alteration is loss of chromosome 22

other genetic events: 9q and 1q gain, loss of 6q, and monosomy 17p

DNA identical to portions of SV40 virus isolated (SV40 – capable of inducing ependymoma in rodents)

Page 42: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Surgical Management..

Key: complete macroscopic surgical resection

Degree of resection is the most significant predictor of survival

Goal of surgery: tissue diagnosis, management of hydrocephalus and cytoreduction

5 years survival after complete surgical resection: 70-80%

If subtotal resection: 5 yr survival – 20-40%

“Second look” surgery if bulky residual tumor after initial surgery

Morbidity of complete resection when CPA extension and 4th ventricular floor involvement is high (10-30%)

Page 43: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Adjunctive therapy..

Radiosensitive tumor hence postoperative radiotherapy

7 yrs EFS and OS of 69% and 81% with maximal surgical resection and local conformational radiation therapy (St. Jude Children’s Research Hospital)

Craniospinal irradiation – only if CSF dissemination by imaging or cytology

Moderate success of chemotherapy, which is used to delay radiation in young children

Current study: molecularly targeted therapy – small molecule tyrosine kinase inhibitors (geftinib, erlotinib, bevacizumab)

Page 44: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Relapse rate: 30-72%

Majority of relapse occurs locally

Median survival time after relapse – 8.4 to 24 months

Literature supports reoperation for recurrence or radiation in children who have not received radiotherapy

Reradiation in children with previous radiation will have high morbidity from radiation necrosis

Page 45: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Atypical Teratoid/Rhabdoid Tumor

Malignant Rhabdoid Tumor – first described as a highly malignant subtype of Wilm’s Tumor

Biggs et al – first intracranial MRT in 1987

Named as atypical teratoid/rhabdoid tumor in landmark paper 1995

Histological character – neuroepithelial, peripheral epithelial and mesenchymal elements

WHO recognized it as a separate tumor entity in 2000

Predominantly a tumor of infants and young children

Median age – 26 months

Slight male predominance

Page 46: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

30% - occur infratentorially (CPA and cerebellum)

22% has CSF dissemination at the time of diagnosis

Overall survival 18 months

If signs of metastasis – 8 months

Page 47: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Histology:

nests or sheets of rhabdoid cells intermixed with areas indistinguishable from PNET or medulloblastoma

histopathological diagnosis aided by staining for the loss of nuclear INI 1 (tumor supressor gene found on chromosome 22q)

60-90% - monosomy or deletions of chromosome 22

Page 48: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Imaging:

no distinguishing features from other fourth ventricular tumor

Page 49: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal
Page 50: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Management:

GTR correlated with OS and PFS

Radiation therapy – craniospinal or focal – important in control

high dose alkylator chemotherapy used with significant benefit in EFS

cisplatin, stem cell rescue and intrathecal chemotherapy

still remains a therapeutic challenge

Page 51: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Choroid Plexus Papilloma and Carcinoma

Rare primary brain tumors arising from choroid plexus epithelium

Guerard described first in 1833

Bielschowsky performed first operative procedure in 1906

0.4 -0.8% of all primary brain neoplasms

70% diagnosed before the age of 2 yrs

Slight male predominance 1-1.3:1

Page 52: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

WHO grades

I – choroid plexus papilloma

II – atypical CPP

III – choroid plexus carcinoma

Anatomically, occurs more frequent in lateral (50-70%), fourth (20-40%) and third (5-10%) ventricles

CPA and biventricular location (5%)

Younger children – lateral ventricle vs. older children 4th vent and CPA

Metastasis – anywhere in neuraxis

Page 53: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Histology and Genetics:

Li-Fraumeni, NF2, Aicardi’s, Down, von-Hipple Lindau – associated

Germline mutation in TP53 and hSNF5/INI1 – familial cases

Gain of 9p and loss of 10q – survival advantage

Histologically similar to normal choroid plexus

Many papillae covered by simple columnar or cuboidal epithelium, eosinophilic cytoplasm, round to oval nuclei situated basally, papillary fronds consisting of vascular stroma

Page 54: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

CPP no necrosis, brain invasion or mitotic figures

CPCmarked cytological atypia, nuclear pleomorphism, loss of

polarity, high cellular density, frequent mitosis, necrosis, vascular proliferation, hemorrhage and brain infiltration

Atypical intermediate degree of nuclear atypia and mitotic figures

Page 55: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Imaging

homogenously enhancing tumor

vascular feeding pedicles

“frond like” solid tumor

associated hydrocephalus

CPCs demonstrate parenchymal invasion and peritumoral edema

Iso to hyperdense on CT with 25% showing calcification

Isointense on T1 and heterogenous on T2 MRI sequence

Page 56: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal
Page 57: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Management:

Extent of surgical resection – significant prognostic factor

Highly vascular tumor – perioperative blood loss add up to morbidity

Preresection chemotherapy used by some group to reduce blood loss

CPP and atypical form treated by gross total resection alone but CPC and if residual tumor in atypical form then adjuvant chemotherapy and craniospinal radiation

Page 58: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Hemangioblastoma..

WHO grade I

Highly vascular tumors seen in cerebellum and spinal cord

Most common posterior fossa lesion in adult but rare in pediatric group

Sporadic or as a part of von Hipple Lindau (VHL) familial syndrome

VHL – autosomal dominant(CNS hemangioblastomas, retinal angiomatosis, pancreatic cyst, renal cell carcinoma, pheochromocytoma and epididymal cyst)

VHL – germline mutation in VHL gene sensor of hypoxia induce vascular remodeling increased levels of VEGF highly vascular tumor

Page 59: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Typically well circumscribed cystic lesion with a small mural nodule abutting pia

But can vary from solid tumor to presence of central cyst

Cyst – hyperintense on both T1 and T2

Strong contrast enhancement of the solid component

Rx – GTR can be curative

If GTR can not be achieved then tumor control by gamma knife radiosurgery or fractionated radiotherapy

Page 60: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Dermoid/Epidermoid Cyst

Rare; <1% ; congenital non-neoplastic lesions arising from retained ectodermal and mesenchymal elements in neural groove during embryonic neural tube closure

Typically present in 3rd decade; rare in pediatric age group

Male predominance

Epidermoid commoner than dermoid (4-10:1); but dermoid commoner in children

Histologically benign but can present with mass effect, aseptic meningitis, infectious meningitis or neurovascular compression

Page 61: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Dermoid – contain both dermal and epidermal elements

typically midline in location

often associated with dermal sinus tract – typical location inion

associated with cutaneous stigmata of hair tufts, cutaneous angioma, and fluid leakage

may be associated with Klippel-Feil syndrome

Page 62: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Epidermoid:

contains epidermal elements

occur in more lateral locations, commonly in CPA

Often called pearly white tumors or cholesteatomas

Dermoids and Epidermoids – well circumscribed lesion with no edema and moderate mass effectHypo and hyperintense on T1 and T2

Epidermoid in CPA mimics Arachnoid cyst; Epidermoid exhibits DWI changes

Page 63: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Rx:

Surgical excision can be curative

Subtotal resection if densely adherent to neurovascular structures

Malignant degeneration to squamous carcinoma is reported but rare

Care not to avoid spillage of contents into the subarachnoid space during surgery aseptic meningitis

Page 64: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Surgical Management of Posterior Fossa tumors

Management of Hydrocephalus

83% of patients with posterior fossa tumor hydrocephalus30% of patients with HCP requires shunt after tumor removalOnly 6% will require shunt if ETV is done prior to removal of tumor

However, with this modality 70% of the children will have to undergo extra surgical procedure

Page 65: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

J Neurosurg Pediatr. 2009 May;3(5):378-85. doi: 10.3171/2009.1.PEDS08298.Predicting postresection hydrocephalus in pediatric patients with posterior fossa tumors.Riva-Cambrin J1, Detsky AS, Lamberti-Pasculli M, Sargent MA, Armstrong D, Moineddin R, Cochrane DD, Drake JM.Riva-Cambrin et. Al Grading system for determining need for postoperative shunt diversion at 6 months:

age < 2yrs - 3 scorepapilledema – 1 scoreinitial degree of hydrocephalus – (moderate to severe) score 2tumor histological features – score 1presence of metastasis – score 3

Scores > or = 5 suggests high risk of developing hydrocephalus

This helps surgeon decide whether or not to do ETV

Currently: option of placing an occipital or “Frazier” burr hole during the surgical procedure for emergent decompression, should post op swelling occur

Page 66: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Surgical Approaches to Posterior Fossa Lesion

Prone position

Slight head rotation if lesion has lateral extension

Sitting posture: blood loss does not pool in the operative field but risk of air embolism

Midline suboccipital craniotomy

Splitting of inferior vermis lateral retraction of the dentate nuclei affects dentatonucleocortical projection cerebellar mutism

Modification: telovelar approach dissection of cerebellomedullary fissure to reach fourth ventricle without splitting the vermis

Page 67: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Telovelar approach

cerebellomedullary fissure opened by separating tonsillo uvular and tonsillomedullary spaces

Uvula retracted superiorly and tonsils laterally

Medullary velum and tela choroidea opened

Inferior roof of fourth ventricle exposed from aqueduct to obex

Opening of tela continued laterally to expose the foramen of Luschka

Posterior arch of C1 can be removed for larger working area and more lateral access

Page 68: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Suboccipital retrosigmoid approach

for lesions in the CPA

allows good visualization of lower cranial nerves and preserves hearing

curvilinear incision made 1-2 cm behind the mastoid

craniotomy performed medial to the sigmoid sinus

arachnoid over the cisterna magna and superolateral cerebellum opened to allow CSF drainage for cerebellar relaxation

care to monitor 7th CN

other more complex approaches like posterior petrosal or far lateral can be utilized in conjunction or separately

Page 69: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Surgical Adjuncts

Image guided surgery or neuronavigation – does not provide real time imaging

Intraoperative MRI

Intraoperative USG

Physiological mapping and monitoring

Mapping – physical stimulation of a brain region of interest awaiting for response; mapping of 4th ventricle for the facial, glossopharyngeal, vagal and hypoglossal nuclei to enhance surgical removal

Monitoring – ongoing activation and recording of neural circuits provide “warnings” of a breach in pathway integrity

50% drop in amplitude or an increased latency of 10% is indicative of pathway injury

Page 70: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Complications of Therapy

1. Cerebellar Mutism – complete absence of speech without impairment of consciousness; other symptoms – hypotonia, ataxia and emotional lability occurs in 25% patients resolution up to 6 months later damage to dentatothalamocortical tracts

2. Cerebellar cognitive affective syndrome

3. Neurocognitive side effects from radiation 20-30 points decrease in IQ with 36 Gy vs 10-15 points decrease with 23.4 Gy

4. Endocrine anomalies

5. Secondary Malignancy – Nonmelanoma skin cancers and benign meningioma

6. Mental health issues, unemployment and remaining single

Page 71: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Brainstem Gliomas

10-15% of primary pediatric intracranial neoplasm

2 decades ago – considered inoperable

Heterogenous group – some of which, amenable to long term survival

Predominantly pediatric entity with mean age of presentation – 7-9 yrs

Focal and exophytic types – low grade with much better prognosis than diffuse high grade

Diffuse Intrinsic Pontine Gliomas (DIPGs) – 60-80% of brainstem gliomas

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Page 75: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Clinical Presentation

Dependent on anatomical location

DIPG rapidly progressive course of cranial neuropathies with

pyramidal tract and cerebellar signs

Focalisolated cranial nerve deficits and contralateral hemiparesis

spanning months to years

Cervicomedullarylower cranial nerve palsies, pyramidal tract signs, ataxia,

spinal cord dysfunction and nystagmus

Tectal tumors – hydrocephalus early due to location near the aqueduct

Page 76: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Diffuse Intrinsic Pontine Glioma

Most common brainstem tumor (60-80%)

Most devastating with median survival of 9 months

Rapid onset and progression

Triad of symptoms (cranial nerve palsies, long tract and cerebellar signs)

Hydrocephalus in advanced stages

Page 77: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Hypointense on T1 and Hyperintense on T2 with indistinct margins reflecting infiltrative nature

Variable Gadolinium enhancement

MRS to delineate it from demyelination, dysmyelination of NF1, encephalitis and radionecrosis

Due to natural history and malignant course very little clinical role for diagnostic biopsy

rationale: all DIPGs are high grade with poor prognosis and biopsy is associated with significant morbidity and mortality rates

May have role in future for targeted therapy

Page 78: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal
Page 79: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Mainstay Rx:

Radiation - 50 Gy

Hydrocephalus (majority – mild) – symptomatic relief with steroid administration

Palliative radiation – symptomatic relief in 75% but eventual recurrence

Page 80: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Focal Brainstem Tumors

Tectal Tumors

5% of brainstem lesions

Typically WHO grade I and II

Hydrocephalus, rapid deterioration and death – even with small size

Second aggressive subtype : > 2cm, invade adjacent tegmentum, thalamus or pons; demonstrate contrast enhancement

Common benign type: well circumscribed and nonenhancing

Page 81: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal
Page 82: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Signs:gait disturbances, ataxia, Parinaud syndrome, strabismus

Rx:Treatment of hydrocephalus and follow up with serial MRI

Some go for more aggressive approach – as 18-30% of tectal tumors progress

GKS – tumor stabilization

management of aggressive variant – debate: biopsy followed by radiotherapy vs complete surgical resection followed by radiation

Page 83: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Dorsally Exophytic Brainstem Tumors

10-20% of brainstem tumors

insiduous onset of headache, vomiting, ataxia and cranial nerve dysfunction (6th and 7th)

papilledema, torticollis and long tract signs

may protrude to 4th ventricle or if dorsolaterally exophytic then to CPA

hypointense T1 and hyperintense T2 with consistent tumor edges due to less infiltrative nature

predominantly pilocytic with occasional grade 2 and 3 and ganglioglioma

Page 84: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Most surgically accessible

Rx:

surgical debulking with serial imaging follow upRadio and chemotherapy – reserved for recurrenceNeuronavigation, DTI, Tractography, brainstem monitoring to maximize resection minimizing morbidity

Page 85: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Cervicomedullary Tumors

Slowly progressive crainal nerve palsies, pyramidal tract signs, ataxia, spinal cord dysfunction, or nystagmus

Lower cranial nerve deficits – dysphagia, nasal speech, nausea, vomiting, palate deviation, facial nerve palsy, head tilt, apnea, or irregular breathing patterns

Histology: pilocytic astrocytoma

Caudal 2/3rd of medulla to rostral portion of cervical spinal cord

Tumor less likely to penetrate the “anatomical barrier” – pyramidal decussating fibers, medial leminiscus, efferent fibers from the inferior olivary complex and inferior cerebellar peduncle

Page 86: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Rx:

Aggressive surgical resection because of well defined surgical plane

Risks: quadriparesis, sleep apnea, CN palsy, proprioceptive defect and spasticity

Radiation therapy can be utilized after surgery, although most wait for evidence of recurrence

Weiner et al (retrospective) – 5 yr PFS 60% and 89% alive even after 5 yrs

Page 87: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Other Focal Brainstem Tumors

<5% in other locations like medulla, midbrain, tegmentum

Anaplastic astrocytoma and GBM have also been described

Non neoplastic lesions – vascular malformations, demyelination and gangliosidoses

Page 88: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Brainstem Gliomas in Neurofibromatosis Type 1

Should not be confused with “unidentified bright objects” in NF1

Bright spots – common and disappears spontaneously

NF1 BSGs – more favorable prognosisSurvival rate – 90% at 5 years age

Page 89: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Role of Surgery in Brainstem Gliomas

Biopsy reserved when indeterminate findings in MRI

Biopsy – complication rate 10-30%

Surgery – role in focal tumors only 4 yrs OS and EFS of 87 & 59%

Perioperative ventilation, tracheostomy and gastrostomy in 41%; almost 80% have eventual complete recovery

Prone positioning

Anterior focal lesion – retrosigmoid approach

Dorsal focal – midline suboccipital approach – telovelar approach

Page 90: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

General Principles

1. Identifying normal anatomy2. Identifying the most direct route to the tumor

(exploring tumor cysts, locating pial surfaces with discoloration from tumor bulge

3. Debulking the center prior to dissecting tumor margins

Neurophysiological monitoringBAER, SSEP, EMG, MEP, neuronavigation

Page 91: Posterior fossa and brainstem tumors in children by Dr. Shikher Shrestha (FCPS), NINAS, Nepal

Thank you!!