CNS Tumors & Infections

Location and Age: The First Clues

Adults above, children below. Most adult primary brain tumors are supratentorial, whereas most childhood tumors are infratentorial (posterior fossa). Posterior fossa masses obstruct the fourth ventricle, causing obstructive hydrocephalus with morning headache, vomiting, papilledema, and ataxia.

Metastases. Metastases are the most common intracranial tumors overall, most often from lung, breast, melanoma, renal, and GI primaries. They are typically multiple, well circumscribed, and located at the gray-white junction, where narrowing vessels trap tumor emboli.

Adult Brain Tumors

Glioblastoma (GBM). The most common malignant primary brain tumor of adults, a WHO grade IV astrocytic tumor that is GFAP positive. It arises in the cerebral hemispheres and can cross the corpus callosum, producing a "butterfly glioma." Histology shows pseudopalisading necrosis (tumor cells lined up around necrotic foci) with microvascular proliferation. Prognosis is grim: median survival is ~15 months with maximal resection plus radiation and temozolomide.

Meningioma. The most common benign adult brain tumor, arising from arachnoid cap cells. It is extra-axial and dural-based, with a dural tail on imaging, and often parasagittal or along the falx. Histology shows whorled spindle cells with psammoma bodies (laminated calcifications). It expresses progesterone receptors, is more common in women, and may present with seizures.

Vestibular schwannoma. Schwannomas are S-100–positive tumors of Schwann cells with alternating cellular (Antoni A) and loose (Antoni B) areas. The classic vestibular schwannoma (acoustic neuroma) sits at the cerebellopontine angle on CN VIII, causing sensorineural hearing loss, tinnitus, and vertigo. Bilateral vestibular schwannomas are pathognomonic for neurofibromatosis type 2 (NF2).

Oligodendroglioma. A slow-growing frontal lobe tumor, often calcified, with round nuclei and clear cytoplasm (fried-egg cells) and delicate chicken-wire capillaries. The 1p/19q co-deletion predicts chemosensitivity and a better prognosis.

Childhood Brain Tumors

Pilocytic astrocytoma. The most common primary brain tumor of childhood: benign (WHO grade I), usually cerebellar, and cystic with a mural nodule. It is GFAP positive with Rosenthal fibers (eosinophilic, corkscrew-shaped fibers) and is BRAF-associated. Prognosis after resection is excellent.

Medulloblastoma. A highly malignant embryonal tumor of the cerebellar vermis and the most common malignant brain tumor of childhood. Sheets of small round blue cells form Homer-Wright rosettes. The midline mass compresses the fourth ventricle, causing hydrocephalus and truncal ataxia, and seeds the CSF, producing drop metastases to the spinal cord.

Ependymoma. Arises from ependymal cells, most often in the fourth ventricle in children, causing hydrocephalus. Histology shows perivascular pseudorosettes and rod-shaped blepharoplasts (basal ciliary bodies) near the nucleus.

Craniopharyngioma. The most common supratentorial tumor of childhood, derived from Rathke pouch (surface ectoderm) remnants, with bimodal age peaks in children and older adults. The suprasellar mass is calcified and contains cholesterol-rich, motor-oil cyst fluid. It compresses the optic chiasm, causing bitemporal hemianopia, and can compress the hypothalamus and pituitary stalk. Histologically it resembles adamantinoma of the jaw, another surface-ectoderm tumor.

CNS Infections

Reading the CSF. Bacterial meningitis produces a high opening pressure and cloudy CSF with thousands of neutrophils, LOW glucose (under ~40 mg/dL or a CSF-to-serum ratio under 0.4), and high protein. Viral (aseptic) meningitis produces clear CSF with lymphocytes, normal glucose, and mildly high protein. Fungal and tuberculous meningitis produce lymphocytes with LOW glucose and high protein.

Neutrophils plus low glucose = bacterial meningitis until proven otherwise; empiric therapy (e.g., ceftriaxone plus vancomycin) should not wait for results.

HSV-1 encephalitis. The most common cause of sporadic fatal encephalitis. Hemorrhagic necrosis of the temporal lobes and orbitofrontal cortex causes fever, altered mental status, seizures, and personality or olfactory changes. CSF shows lymphocytes and red blood cells, and PCR confirms the diagnosis. Start IV acyclovir empirically, before PCR confirmation, because delay increases mortality.

Ring-enhancing lesions. A brain abscess is a ring-enhancing lesion, usually from contiguous spread (otitis, sinusitis, dental infection) involving viridans streptococci, Staphylococcus aureus, and anaerobes, or from hematogenous seeding. In HIV with a CD4 count under 100, multiple ring-enhancing lesions suggest Toxoplasma gondii, whereas a solitary lesion may be primary CNS lymphoma, which is EBV-driven.

Prion Disease

Mechanism. In prion diseases, normal α-helical prion protein (PrP^c) converts to a β-pleated-sheet form (PrP^sc) that is protease-resistant and templates further misfolding. The result is spongiform (vacuolar) degeneration of the cortex without inflammation, because prions are misfolded protein, not microbes.

Creutzfeldt-Jakob disease (CJD). Rapidly progressive dementia with startle myoclonus. CSF 14-3-3 protein and periodic sharp waves on EEG support the diagnosis. Kuru spread through ritual cannibalism, and variant CJD came from eating beef contaminated by bovine spongiform encephalopathy.