Case 22.7 – Intracranial Tumours & Hydrocephalus [SDL]

DIFFERENTIAL DIAGNOSIS:

The clinical picture suggests a POSTERIOR FOSSA LESION with RAISED INTRACRANIAL PRESSURE

Key features pointing to posterior fossa (cerebellum/brainstem):

• Cerebellar signs: Ataxia, past-pointing (dysmetria), nystagmus
• Raised ICP features: Progressive morning headaches, vomiting (worse in morning), papilloedema
• Posterior fossa lesions cause raised ICP more readily due to obstruction of CSF flow (aqueduct, 4th ventricle)

DIFFERENTIAL DIAGNOSES:

1. Posterior Fossa Brain Tumor (MOST LIKELY):

• Subacute progressive symptoms (3 months)
• Cerebellar signs + raised ICP
• Likely tumors in adults (age 39):
  • Metastases: Most common brain tumors in adults; lung, breast, melanoma, renal, colon
  • Hemangioblastoma: Benign cerebellar tumor; can be sporadic or associated with von Hippel-Lindau disease
  • Acoustic neuroma (vestibular schwannoma): Benign tumor of CN VIII; but usually presents with hearing loss, tinnitus, vertigo rather than ataxia
  • Medulloblastoma: More common in children but can occur in adults
  • Ependymoma: Can arise from 4th ventricle
  • Brainstem glioma: Less common in adults

2. Hydrocephalus (Obstructive):

• Could be caused by posterior fossa tumor obstructing 4th ventricle/aqueduct
• Or primary hydrocephalus (aqueduct stenosis, etc.)
• Symptoms: Headache, vomiting, papilloedema, ataxia (gait disturbance from hydrocephalus)

3. Cerebellar Stroke (Hemorrhage or Infarction):

• Usually acute/subacute onset (hours to days, not months)
• Can cause cerebellar signs and raised ICP (mass effect, hydrocephalus)
• Less likely given 3-month progressive history

4. Cerebral Abscess (Posterior Fossa):

• Would expect fever, systemic signs
• Less likely without infective symptoms

5. Demyelination (Multiple Sclerosis):

• Can cause cerebellar signs
• BUT: Usually relapsing-remitting course, not progressive worsening
• Papilloedema uncommon in MS

6. Arnold-Chiari Malformation:

• Congenital hindbrain malformation
• Can present in adulthood with cerebellar signs, headaches
• Less likely with papilloedema

MOST LIKELY DIAGNOSIS: Posterior Fossa Tumor (primary or metastatic) causing obstructive hydrocephalus

INVESTIGATIONS FOR SUSPECTED BRAIN TUMOR:

1. URGENT NEUROIMAGING:

MRI Brain with Gadolinium Contrast:

• Gold standard for brain tumors
• Superior to CT for:
  • Posterior fossa imaging (no bone artifact)
  • Tumor characterization
  • Detecting smaller lesions
  • Assessing extent, edema, mass effect
• With gadolinium contrast: Most tumors enhance (meningioma, metastases, high-grade gliomas); helps differentiate tumor types
• Can assess for hydrocephalus, brainstem involvement

CT Brain with Contrast (if MRI not available/contraindicated):

• Quicker, more accessible
• Can detect tumor, hydrocephalus, hemorrhage
• Less detail than MRI, especially in posterior fossa

2. BLOOD TESTS:

• FBC: Baseline; anemia (chronic disease, bone marrow involvement)
• U&Es, LFTs: Baseline; assess for organ dysfunction
• Coagulation screen: Before biopsy/surgery
• Tumor markers (if metastases suspected):
  • CEA (colon cancer)
  • CA 19-9 (pancreatic, GI)
  • CA 15-3 (breast)
  • PSA (prostate)
  • AFP, β-hCG (germ cell tumors)

3. INVESTIGATIONS TO FIND PRIMARY (if metastases suspected):

• CT Chest/Abdomen/Pelvis: Look for primary tumor (lung, kidney, etc.) or other metastases
• Chest X-ray: Lung cancer screening
• Mammography: If female and suspected breast cancer
• PET-CT: If primary unknown; whole-body imaging to detect occult primary/metastases

4. HISTOLOGICAL DIAGNOSIS:

Biopsy or Surgical Resection:

• Essential for definitive diagnosis and treatment planning
• Options:
  • Surgical resection: For accessible tumors; provides tissue for histology + therapeutic (debulking)
  • Stereotactic biopsy: For deep/inaccessible lesions; less invasive
• Histology determines:
  • Tumor type (WHO classification)
  • Grade (I-IV for gliomas)
  • Molecular markers (IDH mutation, 1p/19q codeletion, MGMT promoter methylation) - guide prognosis and treatment

5. ASSESSMENT OF RAISED ICP/HYDROCEPHALUS:

• Fundoscopy: Papilloedema (already noted in this case)
• Imaging: MRI/CT shows ventricular dilatation if hydrocephalus

6. FUNCTIONAL/COGNITIVE ASSESSMENT:

• Neurological examination: Baseline deficits
• Performance status (Karnofsky or ECOG): Important for treatment decisions
• Cognitive assessment: If symptoms of cognitive impairment

7. OPHTHALMOLOGY REVIEW (if papilloedema):

• Visual field testing
• Visual acuity
• Monitor for optic atrophy (can occur with chronic papilloedema)

CLASSIFICATION OF INTRACRANIAL TUMORS:

Brain tumors can be classified by:

• Primary vs Metastatic
• Cell type of origin (WHO classification)
• Grade (I-IV)
• Location (supratentorial vs infratentorial, intra-axial vs extra-axial)

I. PRIMARY BRAIN TUMORS:

A. GLIOMAS (from glial cells - ~30% of brain tumors, ~80% of malignant brain tumors):

1. Astrocytomas (from astrocytes):

• Grade I (Pilocytic astrocytoma):
  • Benign, slow-growing
  • Common in children/young adults
  • Cerebellum, optic pathway, brainstem
  • Good prognosis; often curable with surgery
• Grade II (Diffuse astrocytoma):
  • Low-grade, slow-growing but infiltrative
  • Young adults (30s-40s)
  • Can progress to higher grade over years
• Grade III (Anaplastic astrocytoma):
  • High-grade, malignant
  • Faster growing
  • Median survival ~2-3 years
• Grade IV (Glioblastoma multiforme - GBM):
  • Most common and most aggressive primary brain tumor in adults
  • Peak age 50-60 years
  • Highly infiltrative, rapid growth
  • Poor prognosis: Median survival ~12-15 months despite treatment
  • Imaging: Ring-enhancing lesion with central necrosis, extensive edema

2. Oligodendrogliomas:

• Arise from oligodendrocytes
• Grade II (low-grade) or Grade III (anaplastic)
• Adults (peak 40-50 years)
• Often frontal lobe
• Better prognosis than astrocytomas (especially if 1p/19q codeleted)
• Imaging: Calcification common

3. Ependymomas:

• Arise from ependymal cells lining ventricles
• Can occur at any age
• Location: 4th ventricle (children), spinal cord (adults)
• Can cause hydrocephalus

B. MENINGIOMAS (~30% of primary brain tumors):

• Arise from meninges (dura mater)
• Usually benign (WHO Grade I ~80%)
• More common in women (2:1); estrogen receptors
• Peak age 60-70 years
• Slow-growing, extra-axial (outside brain parenchyma)
• Common locations: Convexity, falx, parasagittal, sphenoid wing
• Imaging: Homogeneous enhancement, "dural tail" sign
• Treatment: Observation (if small/asymptomatic) or surgical resection
• Rarely malignant (Grade III - atypical or anaplastic meningioma)

C. PITUITARY TUMORS (~15% of brain tumors):

• Arise from pituitary gland
• Adenomas (benign):
  • Functional: Secrete hormones (prolactinoma, GH-secreting, ACTH-secreting, TSH-secreting)
  • Non-functional: No hormone secretion; present with mass effect
• Symptoms: Hormonal (hyperprolactinemia, Cushing's, acromegaly, hypopituitarism) or mass effect (bitemporal hemianopia from optic chiasm compression, headache)
• Treatment: Medical (dopamine agonists for prolactinomas) or surgical (trans-sphenoidal resection)

D. SCHWANNOMAS (~8% of brain tumors):

• Arise from Schwann cells of cranial/spinal nerves
• Vestibular schwannoma (Acoustic neuroma): Most common
  • Arises from CN VIII (vestibulocochlear nerve)
  • Cerebellopontine angle location
  • Symptoms: Unilateral sensorineural hearing loss, tinnitus, vertigo, facial numbness (CN V)
  • Benign but can cause significant morbidity
  • Associated with Neurofibromatosis Type 2 (bilateral acoustic neuromas)

E. MEDULLOBLASTOMAS:

• Highly malignant (WHO Grade IV)
• Most common malignant brain tumor in children
• Arise from cerebellum (vermis or hemispheres)
• Can spread via CSF (drop metastases to spine)
• Treatment: Surgery + craniospinal radiotherapy + chemotherapy

F. CNS LYMPHOMA (Primary CNS Lymphoma - PCNSL):

• Usually B-cell non-Hodgkin lymphoma
• Can occur in immunocompetent or immunocompromised (HIV/AIDS, transplant)
• Deep structures (periventricular, basal ganglia, corpus callosum)
• Imaging: Homogeneous enhancement
• Treatment: High-dose methotrexate-based chemotherapy + radiotherapy

G. OTHER PRIMARY TUMORS:

• Craniopharyngioma: Benign suprasellar tumor; children and adults; can cause pituitary dysfunction, visual field defects
• Hemangioblastoma: Benign cerebellar tumor; adults; associated with von Hippel-Lindau disease
• Germ cell tumors: Pineal region; children/young adults; germinoma, teratoma, etc.
• Choroid plexus tumors: Rare; papilloma (benign) or carcinoma (malignant)

II. METASTATIC BRAIN TUMORS (~50% of all brain tumors in adults):

Most common primary sites:

• Lung (most common - 40-50%)
• Breast (15-20%)
• Melanoma (10% - but melanoma has highest propensity to metastasize to brain)
• Renal cell carcinoma (5-10%)
• Colorectal (5%)

Features:

• Usually multiple lesions (but can be solitary)
• Location: Gray-white matter junction (watershed areas)
• Imaging: Ring-enhancing lesions with surrounding edema
• Prognosis generally poor (median survival months), but depends on primary cancer type, extent, and treatment

ANATOMICAL CLASSIFICATION:

Supratentorial (above tentorium cerebelli):

• Glioblastoma, astrocytoma, oligodendroglioma, meningioma, metastases, pituitary adenoma

Infratentorial (posterior fossa - below tentorium):

• Adults: Metastases, hemangioblastoma, acoustic neuroma, meningioma
• Children: Medulloblastoma, pilocytic astrocytoma, ependymoma, brainstem glioma

Intra-axial (within brain parenchyma):

• Gliomas, metastases, lymphoma

Extra-axial (outside brain parenchyma):

• Meningioma, schwannoma, pituitary adenoma

MOLECULAR CLASSIFICATION (increasingly important for prognosis and treatment):

• Gliomas:
  • IDH mutation status: IDH-mutant has better prognosis than IDH-wildtype
  • 1p/19q codeletion: Oligodendroglioma marker; better prognosis, responsive to chemotherapy
  • MGMT promoter methylation: Predicts response to temozolomide in glioblastoma

HYDROCEPHALUS

Definition: Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) within the ventricles of the brain, leading to ventricular dilatation and raised intracranial pressure.

CSF PHYSIOLOGY (normal):

• CSF produced by choroid plexus in lateral ventricles (~500 mL/day)
• Flows: Lateral ventricles → Foramen of Monro → Third ventricle → Aqueduct of Sylvius → Fourth ventricle → Foramina of Luschka (lateral) and Magendie (medial) → Subarachnoid space → Reabsorbed by arachnoid granulations into venous sinuses
• Normal CSF volume: ~150 mL; turnover ~3-4 times per day

TYPES OF HYDROCEPHALUS:

1. COMMUNICATING HYDROCEPHALUS (Non-obstructive):

• CSF can flow freely through ventricular system (no obstruction)
• Problem: Impaired CSF reabsorption at arachnoid granulations OR rarely overproduction

Causes:

• Post-hemorrhagic: Subarachnoid hemorrhage, intraventricular hemorrhage → blood products block arachnoid granulations
• Post-infectious: Meningitis (especially TB, bacterial) → inflammation blocks reabsorption
• Idiopathic (Normal Pressure Hydrocephalus - NPH): See below
• Venous sinus thrombosis: Impaired venous drainage
• Choroid plexus papilloma: Overproduction of CSF (rare)

2. NON-COMMUNICATING HYDROCEPHALUS (Obstructive):

• Obstruction to CSF flow within ventricular system

Causes by location of obstruction:

• Foramen of Monro: Colloid cyst, tumor
• Aqueduct of Sylvius: Congenital aqueductal stenosis, tectal tumor, aqueductal glioma
• Fourth ventricle / Foramina of Luschka & Magendie: Posterior fossa tumor (medulloblastoma, ependymoma, cerebellar tumor), Chiari malformation, Dandy-Walker malformation

3. NORMAL PRESSURE HYDROCEPHALUS (NPH):

Special type of communicating hydrocephalus in elderly:

• Ventriculomegaly with "normal" CSF pressure (or intermittently elevated)
• Peak age 60-70 years

Classic triad ("Wet, Wobbly, Wacky"):

• Gait disturbance: "Magnetic" gait (feet appear stuck to floor), shuffling, wide-based, freezing; usually FIRST symptom
• Cognitive impairment: Dementia (frontal-subcortical pattern), slowed processing, memory problems, apathy
• Urinary incontinence: Urgency, frequency, incontinence; usually LAST symptom

Diagnosis:

• MRI/CT: Ventriculomegaly out of proportion to sulcal atrophy
• "Tap test": Large-volume LP (30-50 mL CSF removed) → temporary improvement in gait suggests NPH will respond to shunting
• CSF opening pressure normal or mildly elevated (\<20 cm H2O)

Management:

• VP shunt (ventriculoperitoneal shunt): Can improve symptoms in ~50-80%
• Gait improves most; cognition less reliably improved
• Earlier treatment = better outcomes

4. CONGENITAL HYDROCEPHALUS:

• Present at birth or develops in infancy
• Causes: Aqueductal stenosis, neural tube defects (spina bifida with Chiari II malformation), Dandy-Walker malformation, congenital infections (TORCH)
• Symptoms in infants: Increasing head circumference (before fontanelles close), bulging fontanelle, "sun-setting" eyes, irritability, vomiting, lethargy

CLINICAL FEATURES OF HYDROCEPHALUS:

Acute/Symptomatic Hydrocephalus (raised ICP):

• Headache: Worse in morning, worse lying down
• Nausea and vomiting: Especially morning vomiting
• Papilloedema: Swelling of optic discs
• Visual disturbances: Blurred vision, diplopia (CN VI palsy), visual field defects
• Altered consciousness: Drowsiness, confusion, coma
• Cushing's triad (late, pre-terminal): Hypertension, bradycardia, irregular respirations

Chronic Hydrocephalus (NPH, congenital):

• Symptoms as per NPH triad or developmental delay in children

INVESTIGATIONS:

1. Neuroimaging:

• CT Brain: Quick, shows ventricular dilatation, can identify obstruction
• MRI Brain: Better anatomical detail; can identify cause (tumor, aqueduct stenosis, etc.); shows CSF flow
• Key findings:
  • Enlarged ventricles
  • Periventricular lucency (transependymal CSF flow)
  • Effacement of sulci (if raised ICP)

2. Fundoscopy:

• Papilloedema (if acute raised ICP)

3. Lumbar Puncture (ONLY if communicating hydrocephalus and no raised ICP):

• Opening pressure
• Tap test for NPH
• CONTRAINDICATED if obstructive hydrocephalus (risk of herniation)

MANAGEMENT OF HYDROCEPHALUS:

1. TREAT UNDERLYING CAUSE (if possible):

• Tumor resection (if obstructing tumor)
• Treat meningitis/SAH

2. EMERGENCY MANAGEMENT (if acute symptomatic hydrocephalus):

Medical:

• Raise head of bed 30°
• Osmotherapy: Mannitol or hypertonic saline (temporary measure)
• Acetazolamide: Reduces CSF production (limited role; mainly in chronic cases)
• Steroids (dexamethasone): If vasogenic edema from tumor

Surgical (definitive):

• External Ventricular Drain (EVD):
  • Temporary measure for acute hydrocephalus
  • Catheter inserted into lateral ventricle, drains CSF externally
  • Used in emergency or as bridge to definitive treatment
• VP Shunt (Ventriculoperitoneal Shunt):
  • Definitive treatment for chronic hydrocephalus
  • Catheter from lateral ventricle → tunneled under skin → drains CSF into peritoneal cavity
  • Valve regulates flow
  • Complications: Infection, blockage, over-drainage (subdural hematoma), under-drainage
  • May require lifelong
• Endoscopic Third Ventriculostomy (ETV):
  • For obstructive hydrocephalus (e.g., aqueduct stenosis)
  • Creates opening in floor of third ventricle → CSF bypasses obstruction → flows to basal cisterns
  • Avoids need for shunt (no foreign body, lower infection risk)
  • Not suitable for communicating hydrocephalus

3. MONITORING:

• Serial imaging to assess ventricular size
• Neurology/neurosurgery follow-up
• Shunt function monitoring (if shunt in situ)

PROGNOSIS:

• Depends on cause and timing of treatment
• Untreated acute hydrocephalus → herniation → death
• With treatment (shunt), many patients can lead normal lives
• NPH: Earlier treatment = better outcomes; gait improves most
• Congenital hydrocephalus: Variable outcomes; early treatment important to prevent developmental delay