1. rostral end of neural tube fails to close
2. leads to absent cranial vault, brain

• etiology
  • folate deficiency
• pathogenesis
  1. defective closure of caudal end of neural tube
  2. leads to malformed spinal cord and meninges protroduing through bony defect in spinal column and overlying skin

1. deficient posterior fossa volume in developing skull
2. herniation of cerebellar vermis through foramen magnum into cervical spinal canal
3. leads to downward displacement and malformation of brainstem
4. leads to kinks in neural axis above and below posterior fossa
   • medulla overrides cervical spinal cord
   • roof of midbrain protrude back as beak like deformity

Associated with lumbosacral meningomyelocele and hydrocephalus

1. arrested hindbrain development
2. lead to
   • absent or hypoplastic cerebellar vermis
   • cystic dilation of fourth ventricle
   • enlarged posterior fossa
   • hydrocephalus

• astrocytomas
  • circumscribed astrocytomas
  • diffuse infiltrating astrocytomas
• ependymoma
• oligodendroglioma

craniopharyngioma

hemangioblastoma

• medulloblastoma (in cerebellar vermis, IV ventricle)
• astrocytoma
  • diffuse astrocytoma
    • brainstem
    • astrocytoma (grade II)
    • glioblastoma multiforme (grade IV)
  • circumscribed astrocytoma
    • pilocytic astrocytoma (grade I) in cerebellar hemispheres
• ependymoma (in IV ventricle)

Most derived from primitive CNS precursor cells or glia. Most are located in tentorium cerebelli

• most common location- supratentorial
• most common histologic types
  • high grade astrocytoma
    • glioblastoma multiforme (grade IV)
    • anaplastic astrocytoma (grade III)
  • metastatic
  • meningioma
  • pituitary adenoma
  • Schwannoma

• surgical resectability
  • determine by
    • degree of circumsription
    • location

• rarely metastasize beyond CNS
  • CNS does not have lymphatic drainage

• this is a space occupying lesion in a fixed intracranial volume
  • infiltrative, expand/displace normal CNS tissue
  • high grade tumors lack normal CNS BBB
    • cerebral edema around tumor increases mass effect
  • no room to accomadate enlarging tumor
  • increased intracranial pressure, brain herniations

• subfalcine (cingulate)
• transtentorial (uncal, hippocampal)
• tonsillar (cerebellar)

1. expanding frontal parietal mass
2. push cingulate gyrus under falx cerebri
3. compress branches of ACA with infarction of ACA distribution (medial surface of brain)
   • deficits in leg-foot motor sensory area

1. medial most part of temporal lobe (uncus) pushed out over edge of tentorium and wedged into cleft between tentorium and cerebral peduncle of midbrain
   • compress CN III- ipsilateral fixed dilated pupil
   • may push midbrain against contralateral tentorium- ipsilateral hemiparesis from peduncular compression 
   • compress PCA with infarction of PCA distribution (supply occipital cortex)
     • contralateral homonymous hemianopsia with macular sparing

• pathogenesis
  1. inferior most part of cerebellar hemispheres pushed into foramen magnum
  2. compress respiratory centers of medulla
• etiology- tonsillar herniation may result from spinal tap in patient with increase intracranial P
  • check for papilledema
  • obtain CT/MRI before tapping patient with suspected increase in intracranial P

• gliomas
  • astrocytomas
    • circumscribed
    • diffuse
  • ependymoma
  • oligodendroglioma
• embryonal tumors- medulloblastoma

• tumors of meninges- meningioma
• tumors of CN's and spinal nerves
  • schwannoma
  • neurofibroma

• epidemiology- children, adolescents
• common locations
  • cerebellum
  • diencephalon- hypothalamus, optic N./chiasm
• gross appearance
  • NOT diffursely infiltrative of surrounding brain
  • often cystic with tumor nidus in cyst wall ("mural nodule")
• microscopic appearance
  • biphasic pattern
    • fascicles of elongated spindle cells with coarse cytoplasmic processes (piloid cells)
    • loose microcystic zones
• prognosis- use grade I-IV system
  • amenable to surgical excision, long term survival/cure

• astrocytoma (grade II)
• anaplastic astrocytoma (grade III)
• glioblastoma multiforme (grade IV)

• gross appearance
  • poor demarcation from surrounding brain with deep extension into neighboring tissue
• prognosis
  • complete surgical resection often/usually not possible
  • progression of grade II to gade III/IV over time

• two types of clinical presentations
  • brainstem of children
  • cerebral hemisphere white matter in adults < 40 yrs old
• CT/MRI- hypodense lesion without contrast enhancement with minimal/absent edema
• gross pathology
  • no hemorrhage or necrosis
  • gray white poorly demarcated mass expanding or effacing normal architecture
• microscopic pathology
  • hypercellularlity (increased astrocytoma) with nuclear pleomorphism
  • no mitoses, vascular proliferation, necrosis
• prognosis
  • survival of several years after surgery (typically 5-10 yrs)
  • late recurrences often at highe grade
  • eventually death from tumor

• clinical presentation- cerebral hemispheric white matter in adult 40-50
• CT/MRI- low density lesion with irregular contrast enhancement w/ or w/o edema
• gross pathology- SAME AS ASTROCYTOMA
• microscopic pathology
  • hypercellularity
  • pleomorphism
  • mitoses
• prognosis
  1. recurrence after surgery in 12-24 mnths
  2. progression to grade IV
  3. death from tumor

• clinical presentation
  • cerebral hemispheric white matter in adults > 50 yrs old
  • brainstem of children
• CT/MRI
  • heterogeneous, hyperdense lesion
  • peripheral rim of contrast enhancement (ring enhancement)
  • significant peritumoral edema and "mass effect"
    • ventricular effacement
    • shift of midline structures
• gross pathology
  • hemorrhage, necrosis
  • may cross to contralateral hemisphere in corpus callosum (butterfly glioma)
• microscopic pathology
  • hypercellularity, pleomorphism, mitoses, vascular proliferation, necrosis
    • necrotic areas surrounded by radially arranged still viable tumor cells (palisade)
• prognosis
  • death from tumor in 12-24 months
  • adjuvant radiation therapy may prolong survival by several months

• clinical presentation
  • IV ventricle in children
  • spinal cord of adults
    • special myxopapillary variant in lumbosacral cord with favorable prognosis (grade I)
• gross pathology
  • solid/papillary intraventricular tumor
  • relatively circumscribed intramedullary spinal cord mass
    • better circumscribed than diffuse astrocytomas, but still tend to recur
• CT/MRI
  • heterogeneously enhancing IV ventricular or spinal cord mass, sometimes with calcification
• microscopic pathology
  • glial tumor
  • perivascular pseudorossetes
  • with or without ependymal canals
• prognosis
  • survival depends on age, location, resectability
  • survival shorter/worse prognosis with:
    • kids
    • intracranial location
    • incomplete resection
  • recurrence, dissemination in CSF

• clinical presentation- cerebral hemispheric white matter of adults
• CT- calcification common and may follow cortical ribbon in serpiginous pattern
• gross pathology
  • gray pink mass with cysts, calcification, hemorrhage
• microscopic pathology
  • uinform cells with clear cytoplasm and central nuclei (fried eggs)
  • acutely branching capillary stroma (chicken wire vasculature)

• clinical presentation
  • cerebellar vermis tumor in children
  • originates from primitive precursor cells, probably in cerebellar external granular cell layer
• CT/MRI- hyperdense contrast enhancing lesion
• gross pathology
  • variable circumscription
  • gray-white to hemorrhagic
• microscopic pathology
  • small round blue cell tumor
    • cells with high N/C ratio
    • Homer-Wright rosettes
    • high mitotic activity, apoptosis, pleomorphic
    • may show neuronal and/or glial differentiation
• prognosis
  • surgery plus radiation/chemo increases chances of survival in 5 yrs to 50-70%
  • possible recurrence, dissemination in CSF

• origin- extra-axial tumor derived from arachnoid cap cell of leptomeninges
• clinical presentation
  • attached to dura over cerebral convexity, falx cerebri, base of skull (sphenoid wing, petrous ridge, clivus, foramen magnum), spinal canal
  • adult patients with female predominance
• CT/MRI
  • extra-axial isodense mass with contrast enhancement
  • may show streak of enhancement trailing off from main tumor ("dural tail")
• gross pathology- well circumscribed firm gray-white mass anchored on dura
• microscopic pathology
  • architecture composed of varying proportion of spindles and whirls
  • minimal pleomorphism, mitotic activity
  • may see round concentric calcification (Psammoma bodies)
• pathogenesis
  1. slow growth over long period
  2. can entrap spinal/cranial nerves, bv's
  3. may infiltrate dural venous sinuses and overly bone with secondary bone thickenin (hyperostosis)
     • progesterone R's may be present

• allelic loss of chromosome 22 leads to activation of NF2 oncogene
  • multiple meningiomas

• clinical presentation
  • cerebellopontine angle tumor in adults with hearing loss
    • vestibular schwannoma)
  • spinal canal, attached to nerve root (usually dorsal) with nerve root compression
• gross pathology
  • well circumscribed, encapsulated, attached to nerve root
  • may show degenerative changes (cysts, hemorrhage)
• microscopic pathology
  • biphasic with dense (antoni A) and loose (antoni B) zones
  • alignment of nuclei with plisades (verocay bodies)
  • parent nerve pushed to one side
• prongosis
  • slow growth over loong period
  • surgically curable
  • may affect peripheral nerves
• genetics- multiple schwannomas characteristic of neurofibromatosis type 2

• gross pathology
  • unencapsulated, diffuse fusiform expansion of nerve
  • soft with shiny gelatinous cut surface
• microscopic pathology
  • loose myxoid background with small wavy or comma shaped schwann cell nuclei
  • axons of parent nerve embedded in, separated by, tumor
• prognosis
  • slow growth over long peroid
  • may affect peripheral nerves and terminal nerve branches in skin
• genetics- multiple neurofibromas characteristic of neurofibromatosis type I
  • nerve sheath tumors in NF1 may become malignant

• Lung
• Breast
• Skin (melanoma)
• Kidney
• GI

think "Lots of Bad Stuff Kills Glia"

• multiple CNS tumors
  • gray-white junction of cerebral hemispheres favored site, but may occur anywhere
  • diffuse spread in subarachnoid space (carcinomatous meningitis)
  • dural infiltration (breast, prostate)

• CT/MRI- multiple heterogeneous masses with contrast enhancement and surrounding edema
• gross pathology- circumscribed tumors with necrosis, hemorrhage
• microscopic pathology- histology same as primary neoplasm
• prognosis
  • influenced by number and location of metastases, sensitivity of primary tumor to therapy
  • medial survival with multiple brain metastases treated with radiation 3-6 months