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Lumbar puncture allows for the evaluation of the following parameters in the cerebrospinal fluid (CSF) (Table 2–2):
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CSF pressure
CSF chemistry: glucose and protein
CSF cell counts and types: red and white blood cells, cytology, flow cytometry
CSF microbiology: cultures, polymerase chain reaction (PCR), and antibodies
Special studies:
Oligoclonal bands (see Ch. 21)
Paraneoplastic antibody panels (see Ch. 24)
Biomarkers for neurodegenerative diseases (e.g., Aβ-42, tau, 14-3-3) (see Ch. 22)
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CSF pressure is ascertained by attaching a manometer to the spinal needle. Measurement of CSF pressure should be made with the patient in the lateral decubitus position with the legs extended. Normal pressure is below 20 cm H2O (200 mm H2O). CSF pressure can be elevated due to any process raising intracranial pressure (intracranial hypertension), and can be decreased in any condition decreasing intracranial pressure (intracranial hypotension) (see Ch. 25).
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CSF Chemistry: Glucose and Protein
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CSF glucose should be approximately 60% of serum glucose. CSF glucose can be decreased in bacterial, fungal, and tubercular CNS infections (but not viral infections; see Table 20–2), as well as with leptomeningeal metastases (see Ch. 24). Hypoglycorrhachia is the technical term for decreased CSF glucose. Although the reason for decreased CSF glucose in CNS infections is sometimes taught as the “infectious pathogens consuming the glucose,” decreased CSF glucose in infection may be due to a combination of factors including impaired transport into the CSF in infectious states involving the meninges, CNS hypermetabolism in infectious states, and consumption of glucose by white blood cells.
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A rare cause of decreased CSF glucose is GLUT1 deficiency, a rare genetic cause of infantile epilepsy due to a defect in a transporter of glucose (GLUT1) across the blood–brain barrier.
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Increased CSF glucose can be seen when there is serum hyperglycemia.
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CSF protein should normally be less than 50 mg/dl. CSF protein can be elevated in any inflammatory or infectious state. CSF protein may also be elevated when there is obstructed circulation of CSF due to spinal lesions (spinal block); when extreme, this may cause the CSF to coagulate in the test tube (Froin’s syndrome).
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CSF Cell Counts and Cell Types
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White Blood Cells in the CSF
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The normal range of white blood cells (WBCs) in the CSF is 0–5 WBCs/mm3. Increases in CSF WBC count can occur due to CNS infection, inflammation, and CNS hematologic malignancy (e.g., CNS lymphoma).
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Polymorphonuclear cells (neutrophils) predominate in bacterial meningitis but may also be seen early in viral meningitis/encephalitis, whereas lymphocytes are commonly seen in viral, fungal, and tubercular CNS infections, CNS inflammation, and lymphoma. Flow cytometry can be used to characterize WBC populations in the CSF to evaluate for hematologic malignancy. Cytology can examine cells to look for malignant cells as can be seen in CNS lymphoma and leptomeningeal metastases from systemic cancer (see Ch. 24).
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Red Blood Cells in the CSF
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The normal range of RBCs in the CSF is 0–5 RBCs/mm3. Elevated RBC can be seen in subarachnoid hemorrhage (see Ch. 19) or if a lumbar puncture is traumatic, causing bleeding into the CSF (see “Traumatic Lumbar Puncture” below). If blood is present from subarachnoid hemorrhage, it will have been present in the CSF for some time and RBCs will have begun to break down. In contrast, a traumatic lumbar puncture will yield fresh RBCs that have not yet had the time to break down. Xanthochromia, a yellow tinge to the CSF (more sensitively detected by spectrophotometry) is an indication of broken-down red blood cells in the CSF, suggesting that they were there prior to the lumbar puncture (i.e., suggestive of subarachnoid hemorrhage rather than traumatic lumbar puncture).
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CSF Microbiology: Cultures, PCR, and Antibodies
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Examination of CSF for a pathogen causing CNS infection can include Gram stain, culture, PCR, and evaluation for CSF production of IgM or IgG against a particular pathogen (see Ch. 20).
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Patterns of CSF Abnormalities
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Several patterns of CSF abnormalities are important to recognize.
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Elevated Protein With No or Few Cells (Albuminocytologic Dissociation)
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Albuminocytologic dissociation is suggestive of an inflammatory process. While this pattern is generally learned by most medical students as the classic finding in Guillain-Barré syndrome, it is a nonspecific indicator of inflammation and can be seen in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP; Ch. 27), CNS paraneoplastic conditions (Ch. 24), acute disseminated encephalomyelitis (Ch. 21), transverse myelitis (Ch. 21), and primary CNS vasculitis (Ch. 19). (Why does the CSF demonstrate an inflammatory pattern in peripheral nervous system disorders such as Guillain-Barré syndrome and CIDP? These disorders involve the nerve roots which pass through the CSF space.)
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Elevated WBCs and Protein With Normal Glucose
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This is suggestive of a viral process.
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Elevated WBCs and Protein With Low Glucose
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This pattern generally indicates a nonviral CNS infection (bacterial, fungal, or tubercular). The most extreme values for low glucose, elevated WBCs, and elevated protein are seen with CNS bacterial infections.
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In CNS bacterial infections, the WBCs are predominantly neutrophils, whereas they are predominantly lymphocytes in other types of CNS infections (see Table 20–2 in Ch. 20).
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Traumatic Lumbar Puncture
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Elevations of protein and WBCs can occur in a traumatic lumbar puncture since there is contamination of the CSF with peripheral blood. Protein elevation and WBC elevation are both approximately 1 per 1000 RBCs (1 mg/dL of protein per 1000 RBCs/mm3, and 1 WBC/mm3 per 700–1000 RBCs/mm3).
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Additional Tests of CSF
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Oligoclonal bands are a nonspecific marker of CNS inflammation, denoting intrathecal synthesis of IgG. Although they are most commonly assessed in the evaluation for multiple sclerosis (see Ch. 21), they can be seen in any CNS infectious or inflammatory condition.
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CSF evaluation for antibodies causing CNS paraneoplastic syndromes (e.g., paraneoplastic limbic encephalitis, paraneoplastic cerebellar degeneration; see Ch. 24) is often more sensitive than serum evaluation.
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14-3-3 protein is a nonspecific marker of neuronal degeneration. Although it can be present in Creuzfeldt-Jakob disease, the test is neither sensitive nor specific for the condition (see Ch. 22).
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The ratio of amyloid-beta 42 (Aβ-42) to tau is a biomarker for Alzheimer’s disease, discussed further in Chapter 22.