CSF
Summary
Cerebrospinal fluid (CSF) is a clear, colorless ultrafiltrate-like fluid produced mainly by the choroid plexus ependymal cells in the ventricles. It cushions and supports the brain, maintains chemical homeostasis, and clears waste. Lumbar puncture analysis (cell count, protein, glucose, opening pressure) is key for diagnosing meningitis, SAH, Guillain-Barré syndrome, MS, and idiopathic intracranial hypertension.
Detail
PRODUCTION AND FLOW: CSF is made by ependymal cells of the choroid plexus (~500 mL/day; total volume ~150 mL in adults, turned over about 3-4x/day). Production uses active secretion (Na+/K+-ATPase, carbonic anhydrase), so acetazolamide (carbonic anhydrase inhibitor) decreases CSF production. Flow: lateral ventricles → foramina of Monro → third ventricle → cerebral aqueduct (of Sylvius) → fourth ventricle → foramina of Luschka (lateral) and Magendie (median) → subarachnoid space → reabsorbed by arachnoid granulations into the dural venous sinuses (superior sagittal sinus).
BARRIERS: The blood-CSF barrier is formed by tight junctions between choroid plexus ependymal cells. The blood-brain barrier is formed by capillary endothelial tight junctions, astrocyte foot processes, and the basement membrane. Both limit passage of many substances.
FUNCTIONS: Buoyancy (reduces effective brain weight from ~1400 g to ~25 g), mechanical protection, chemical stability, nutrient delivery, and waste removal (glymphatic system, most active during sleep).
NORMAL VALUES (adult): Opening pressure 70-180 mm H2O (lumbar puncture, lateral decubitus position). WBC 0-5 cells/µL (lymphocytes/monocytes). Protein 15-45 mg/dL. Glucose about 60% of serum glucose (roughly 45-80 mg/dL). RBC: none. The fluid is clear and colorless.
LUMBAR PUNCTURE: Needle passes through skin, subcutaneous tissue, supraspinous and interspinous ligaments, ligamentum flavum, epidural space, dura, and arachnoid into the subarachnoid space. It is done at L3-L4 or L4-L5 (the line between iliac crests, the intercristal line, is at L4), below the conus medullaris (L1-L2 in adults). Contraindications: mass lesion or elevated ICP with risk of herniation (get imaging first), coagulopathy or thrombocytopenia, and skin infection at the site.
CSF PATTERNS: - Bacterial meningitis: High neutrophils (often >1000), high protein, low glucose, high opening pressure. Common organisms: S. pneumoniae, N. meningitidis (adults); GBS, E. coli, Listeria (neonates); Listeria also in the elderly and immunocompromised. - Viral (aseptic) meningitis: Lymphocytic pleocytosis, mildly high protein, normal glucose (enteroviruses most common; HSV-2 can cause recurrent Mollaret meningitis). - Fungal/TB meningitis: Lymphocytes, high protein, low glucose. Cryptococcus: India ink stain or cryptococcal antigen; very high opening pressure may require serial LPs. TB: basilar enhancement and cranial nerve palsies. - HSV encephalitis: Lymphocytes plus RBCs (temporal lobe hemorrhagic necrosis); diagnose with PCR and treat with IV acyclovir. - Subarachnoid hemorrhage: Xanthochromia (bilirubin from RBC breakdown, appears ~6-12 hours after bleed) and RBCs that do not clear from tube 1 to tube 4. CT head is the first test (most sensitive within 6 hours). - Guillain-Barré syndrome: Albuminocytologic dissociation (high protein with normal cell count). - Multiple sclerosis: Oligoclonal IgG bands, elevated IgG index, and increased myelin basic protein. - Idiopathic intracranial hypertension: High opening pressure with normal CSF composition (young obese women, papilledema, headache, vision changes). Treat with weight loss, acetazolamide, and serial LPs or shunting if severe. - Normal pressure hydrocephalus: Normal opening pressure; triad of "wet, wobbly, wacky" (urinary incontinence, gait apraxia, dementia). Ventriculomegaly with a normal CSF profile; treat with VP shunt. - Neurosyphilis: Positive VDRL (specific, not sensitive) in CSF. - Other: Elevated 14-3-3 protein in Creutzfeldt-Jakob disease (also RT-QuIC); low Aβ42 and high tau/phospho-tau in Alzheimer disease.
HYDROCEPHALUS: - Communicating (non-obstructive): Impaired reabsorption at arachnoid granulations (e.g., post-meningitis, SAH). Normal pressure hydrocephalus is a subtype. - Non-communicating (obstructive): Blockage within the ventricular system (e.g., aqueductal stenosis, Dandy-Walker malformation, posterior fossa tumors, Chiari II). - Hydrocephalus ex vacuo: Brain atrophy causes ventricle enlargement, but ICP is normal (e.g., Alzheimer disease, advanced HIV, Pick disease).
HERNIATION AND ICP: Elevated ICP causes Cushing triad (hypertension, bradycardia, irregular respirations). Herniation types: subfalcine (cingulate gyrus under falx; ACA compression), uncal/transtentorial (CN III palsy, "blown pupil," contralateral hemiparesis, Duret hemorrhages in the midbrain/pons), and tonsillar (cerebellar tonsils through foramen magnum; medullary compression, death).
CLINICAL PEARLS: Post-LP headache arises from CSF leak and is positional (worse upright); treat with fluids, caffeine, then epidural blood patch. CSF rhinorrhea or otorrhea after skull base fracture can be confirmed by beta-2 transferrin. In neonates, the choroid plexus is a site for papillomas (hydrocephalus from overproduction in children).
Sources
- First Aid for the USMLE Step 1 (Neuroscience: ventricular system, CSF; Microbiology: meningitis)
- Pathoma (Fundamentals of Pathology) – CNS pathology
- Kaplan USMLE Step 1 Lecture Notes: Neuroscience
- Kandel ER et al., Principles of Neural Science
- Harrison's Principles of Internal Medicine – CSF analysis and lumbar puncture
- UpToDate – Lumbar puncture: indications, contraindications, technique, and complications in adults
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