Chapter 2: Introduction to Neuroimaging and Cerebrospinal Fluid Analysis

Neurodiagnostic tests aid in determining both localization and diagnosis. The main neurodiagnostic tests are: neuroimaging, cerebrospinal fluid (CSF) analysis, electroencephalography (EEG), and electromyography/nerve conduction studies (EMG/NCS). EEG is discussed in the context of the diagnosis of seizures and epilepsy (Ch. 18) and EMG/NCS in the context of the diagnosis of neuromuscular disease (Ch. 15 for the principles; Chs. 16–17 and 27, 28, 29, 30 for clinical use). Neuroimaging and CSF analysis are discussed throughout this book, but an introduction to their use and interpretation is provided here.

Neuroimaging allows for visualization of the structures of the neuraxis, and is used as an extension of the neurologic examination. If a patient’s symptoms and signs localize to a particular part of the neuraxis, neuroimaging of that region can provide additional information about the underlying pathologic process. The disease-based chapters of Part 2 of this book discuss when neuroimaging should be obtained with regard to particular symptoms and diseases, and how it can aid in diagnosis of various neurologic conditions.

In clinical practice, many patients have undergone neuroimaging studies before a neurologist has evaluated them, and some patients may be referred for neurologic evaluation because of neuroimaging findings rather than clinical findings. In such scenarios, part of the clinical reasoning process is interpreting the neuroimaging in the context of the clinical findings: Do the neuroimaging findings correlate with the patient’s clinical presentation? Are there aspects of the patient’s clinical presentation that do not have a neuroimaging correlate? Are there incidental findings that have no relationship to the patient’s current presentation but require further evaluation or longitudinal clinical and radiologic surveillance? Whether neuroimaging is obtained and reviewed before evaluation of a patient or in the process of a patient’s evaluation, neuroimaging must always be interpreted in the context of the patient’s history and physical examination in order to prevent misinterpretation/overinterpretation/underinterpretation of radiologic findings.

The cornerstones of neuroimaging of the nervous system are computed tomography (CT) and magnetic resonance imaging (MRI), both of which can be performed with or without intravenous contrast, and both of which can be used to evaluate the cerebral vessels (CT angiography [CTA] and venography [CTV]; MR angiography [MRA] and venography [MRV]). More specialized radiographic techniques used in the evaluation of neurologic diseases include CT and MR perfusion studies, MR spectroscopy, nuclear imaging (positive emission tomography [PET] and single photon emission computed tomography [SPECT]), and transcranial Doppler ultrasound.

What follows is a primer on neuroimaging. It is not intended to be of sufficient scope and detail for radiologists and radiology trainees, but is meant to provide the clinician with an approach to interpreting neuroimaging studies of the brain and spinal cord (bone and extracranial soft tissues are not discussed).

Whether using CT or MRI, and whether evaluating the brain or spine, the two main goals are as follows:

1. Identification of normal structures and any disturbance or distortion of these structures: Is everything there that is supposed to be there, and does it look as it is supposed to look?

   • Are tissue structures of normal size or is there atrophy or expansion of one or more regions of the brain or spinal cord?

   • Are the fluid compartments of normal size and configuration (i.e., ventricles, cisterns, sulci of brain; central canal of spinal cord)?

   • Are structures where they are supposed to be or is there herniation (displacement of structures beyond their normal compartments)?

2. Identification and characterization of abnormal lesions: Is there anything there that should not be there, and if so, how can it be characterized?

   • CT: Are there regions of hypodensity (darker than normal tissue density) or hyperdensity (brighter than normal tissue density)?

   • MRI: Are there regions of hypointensity (darker than normal tissue intensity) or hyperintensity (brighter than normal tissue intensity)?

When interpreting neuroimaging studies, it is helpful to begin by scrolling once from top to bottom and then from bottom to top through all obtained sequences, first taking inventory of normal structures and abnormal findings, and then characterizing them in radiographic terms before interpreting them (e.g., “There is a hypodensity spanning the left frontal and temporal lobes with sharply demarcated borders and no other apparent abnormalities.”). This will allow for an initial radiologic differential diagnosis that can be aligned with the clinical presentation and will avoid potentially premature conclusions (e.g., focusing on an obvious abnormality at the expense of not noting other more subtle abnormalities or global abnormalities).

The easiest neuroimaging abnormalities to see are asymmetries (e.g., a lesion on one side that contrasts with the normal contralateral side). It can be more challenging to note symmetric abnormalities (e.g., diffuse cerebral edema, symmetric ventriculomegaly, symmetric atrophy), especially when first learning to interpret neuroimaging. This skill emerges over time after reviewing a large number of normal and abnormal studies (just as appreciating what the range of normal is for a physical examination finding such as reflexes requires examining a large number of patients).

The main neuroimaging modalities used to examine the brain and spine are CT and MRI. Noncontrast CT has the advantages of being able to be completed rapidly and being better at analyzing abnormalities of bone. It may be more sensitive than MRI for detecting acute intracranial hemorrhage, but is less sensitive for identifying subtle pathologic changes and is particularly insensitive in the posterior fossa (due to beam hardening artifact). MRI has several advantages: greater resolution than CT, increased ability to detect small and/or subtle abnormalities that may not be visible on CT, ability to use different MRI sequences (discussed below) to allow for abnormalities to be viewed in different ways (which aids in characterizing them), and no radiation exposure. Compared to CT, MRI takes longer to perform, is more expensive, and cannot be performed in patients with cardiac pacemakers, other implanted ferromagnetic medical devices, or exposure to shrapnel.

CT can be viewed using different windows that highlight different aspects of the image (e.g., brain vs bone) (Fig. 2–1). CT relies on differences in density of tissues to generate an image. Denser tissues (and some pathologic findings) are brighter (hyperdense), whereas less dense tissues (and some pathologic findings) are darker (hypodense). At the extremes, bone is the most dense structure on a head CT and appears the brightest, while air (e.g., in the sinuses) is the least dense and is therefore the darkest. CSF is denser than air but not as dense as brain. Brain is denser than CSF. Within the brain, the gray matter is denser than the white matter, so the cortex and deep gray matter structures (basal ganglia and thalamus) are slightly brighter than white matter. The most common CT window used by neurologists is the brain window, which allows for these various structures to be identified and differentiated, but is less sensitive for noting bony abnormalities (e.g., fractures), which are best visualized using the bone window.

Abnormal brain CT findings (e.g., beyond changes in the shape or size of normal structures such as atrophy, ventricular enlargement) can be classified as hyperdensities or hypodensities.

Causes of Hyperdensity on Brain CT

The most common causes of hyperdensity in the brain on CT are hemorrhage and calcification (Fig. 2–2). Contrast enhancement is also hyperdense (see “Contrast-Enhanced Neuroimaging” below). The distinction between hemorrhage and calcification as a cause of a CT hyperdensity can generally be made in the context of the clinical history (e.g., acute-onset focal deficits with a corresponding hyperdense lesion suggests hemorrhage), but if there is doubt, Hounsfield units can be determined (60–100 for blood, 100–200 for calcification; for reference, bone is typically greater than 1000). Calcifications may represent normal findings (e.g., in the choroid plexus, in the falx cerebri, in the pineal gland, and in some older individuals in the basal ganglia). Pathologic hyperdensities on brain CT can be caused by:

• Acute intracranial hemorrhage (intraparenchymal, intraventricular, subarachnoid, subdural, epidural; see Ch. 19)

• Calcification (tumors or infectious lesions may have calcified components; e.g., neurocysticercosis)

• Hypercellular tumor (e.g., lymphoma)

• Thrombosed blood vessel (e.g., hyperdense vessel sign in acute ischemic stroke and cord sign in venous sinus thrombosis [Ch. 19])

• Atherosclerotic plaques within arteries

• Contrast-enhancing lesions such as tumor, abscess, acute demyelination, subacute stroke (see “Contrast-Enhanced Neuroimaging”)

Causes of Hypodensity on Brain CT

Pathologic hypodensities on brain CT can be caused by (Fig. 2–3):

• Any type of pathology that causes vasogenic edema: tumor, inflammation, infection, trauma, ischemic stroke (although CT may be normal in the acute phase of ischemic stroke; see Ch. 19)

• Sequelae of prior injury (trauma, infarct, demyelinating lesion)

The differential diagnosis for a discrete region of hypodensity on brain CT includes stroke, tumor, inflammatory lesion, and infectious lesion. Since strokes respect a vascular territory, the hypodensities that they cause generally have clear, distinct borders. In contrast, edema around a tumor, infectious lesion, or an acute demyelinating lesion typically has less distinct boundaries. Additionally, if the hypodensity in question is near the cortical surface, an infarct will most often include the cortex since a cortical vessel will supply both the cortex and the underlying white matter. In contrast, most neoplastic, infectious, and demyelinating lesions involve the subcortical white matter and, therefore, the hypodensity caused by such lesions will usually respect the gray–white boundary, sparing the overlying cortex (Fig. 2–3).

The main clinically important MRI sequences for evaluating the brain are T1, T2, FLAIR, DWI and ADC, and SWI (or GRE) (Fig. 2–4). These sequences differ in the way they are acquired in order to allow for visualization of different types of pathology.

T1-weighted, T2-weighted, and FLAIR MRI Sequences

On T1-weighted images, the gray matter appears darker than the white matter, and the CSF is dark. T2-weighted images appear like a “negative” of the T1-weighted images: white matter is darker than gray matter, and CSF is bright. Most types of pathology in the brain show up as bright (hyperintense) on T2-weighted images and dark (hypointense) on T1-weighted images (e.g., stroke, tumor, infection, edema, demyelination).

The FLAIR (fluid-attenuated inversion recovery) sequence is a T2-weighted sequence with suppression of the bright CSF signal. By suppressing the bright CSF, the FLAIR sequence makes T2-hyperintense pathology in the brain more easily visible. For example, hyperintensity immediately adjacent to the ventricles may be difficult to visualize on T2-weighted images since the CSF is bright and may make it difficult to distinguish periventricular hyperintensities. FLAIR images resolve this problem by suppressing the CSF signal in the ventricles to make periventricular signal abnormalities more easily visible (Fig. 2–5). T2 hyperintensities in the brainstem may be more effectively visualized on T2-weighted images than on FLAIR images.

In general, T1 images are used to examine brain structure, and T2/FLAIR images are used to look for hyperintensities suggestive of pathology. When contrast is administered, postcontrast T1-weighted images are compared to precontrast T1-weighted images to look for abnormal regions of enhancement (see “Contrast-Enhanced Neuroimaging” below).

As described above, acute blood on CT is bright (hyperdense). On MRI, blood has different appearances on T1 and T2 sequences depending on the age of the blood, which can therefore help to determine the age of an intracranial hemorrhage (Table 2–1).

Diffusion-Weighted Imaging and Apparent Diffusion Coefficient MRI Sequences

Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) sequences evaluate the ease with which water can diffuse through tissue (Fig. 2–6). The appearance of DWI sequences can be distinguished from T1 and T2 images by the fact that the brain anatomy is much less well defined on DWI and the skull is not visible on DWI. Areas where water diffuses less easily are said to demonstrate diffusion restriction. Regions of diffusion restriction appear bright on DWI and dark on ADC. Foci that are bright on DWI but not dark on ADC do not represent true restricted diffusion (referred to as T2 shine-through if also bright on T2/FLAIR, but may also represent artifact).

DWI and ADC sequences are most commonly used in the evaluation of acute ischemic stroke (Ch. 19), since acute ischemia may be visible within minutes on DWI and ADC, significantly earlier than any other MRI sequence (the cause of diffusion restriction in acute ischemic stroke is cytotoxic edema). In addition to stroke, diffusion restriction can be seen in Creutzfeldt-Jakob disease (in the cortical ribbon and basal ganglia [Ch. 22]), hypercellular lesions (e.g., abscess [Ch. 20], primary central nervous system lymphoma [Ch. 24]), and in the setting of seizures (Ch. 18).

Susceptibility-Weighted Imaging and Gradient Echo MRI Sequences

Susceptibility-weighted imaging (SWI) and gradient echo (GRE) sequences are mostly used to evaluate for blood, which is dark on these sequences (Fig. 2–7). Calcification is also dark on SWI/GRE sequences. These sequences are particularly sensitive for detecting microhemorrhages (e.g., in the evaluation for cerebral amyloid angiopathy [Ch. 19]) and may also reveal a thrombosed blood vessel in the setting of acute ischemic stroke or cortical vein or venous sinus thrombosis (Ch. 19).

MR Spectroscopy

MR spectroscopy (MRS) quantitatively evaluates brain metabolites (Fig. 2–8). The most common clinically relevant metabolites examined are N-acetyl aspartate (NAA) and choline. NAA can be thought of as a measure of neuronal health (higher NAA = healthier neurons; lower NAA = diseased neurons), and choline as a marker of membrane turnover. Decrease in the NAA peak is nonspecific, but the combination of decreased NAA peak and increased choline peak is suggestive of glial neoplasm (although this pattern can also be seen in acute demyelination). Normally, the NAA peak towers over the choline peak, and the angle of a line drawn between them (Hunter’s angle) is about 45 degrees. With glial neoplasms, the choline peak becomes equal to or rises above the NAA peak. Other MRS findings that may be useful in neurologic diagnosis are increased lactate (which can occur with tumor, ischemic stroke, mitochondrial disease) and increased NAA (which can occur in Canavan’s disease [see Ch. 31]).

Contrast administration can further improve the sensitivity of neuroimaging in detecting abnormalities, and can also improve the specificity with which the etiology of such abnormalities can be determined (Fig. 2–9). CT uses iodinated contrast, and MRI uses gadolinium contrast. Blood vessels normally enhance with contrast administration, but if the meninges or brain parenchyma enhance, this suggests breakdown of the blood–brain barrier, allowing contrast to leak into these tissues. Contrast enhancement can occur in the setting of tumor, infection, inflammation, and in the subacute period after infarction. Contrast-enhanced images should always be compared to analogous images without contrast: CT with contrast should be compared to noncontrast CT; T1-weighted postcontrast MRI sequences should be compared with T1-weighted precontrast sequences. This is important so that a region that is hyperintense on T1 (or hyperdense on CT) without contrast is not mistakenly presumed to enhance with contrast if the region’s intrinsic hyperintensity/hyperdensity is not noted on the precontrast image.

Many tumors and infectious lesions show a complete rim of enhancement, whereas demyelinating lesions may show open-rim or C-shaped regions of enhancement (see Ch. 21).

Contrast enhancement in the meninges can be characterized as leptomeningeal (affecting the pia and arachnoid) or pachymeningeal (affecting the dura) (Fig. 2–10). Leptomeningeal enhancement follows the contour of the surface of the brain, extending into the cerebral sulci and cerebellar folia. Pachymeningeal enhancement appears as a rim around the outer surface of the brain without invaginating into the sulci; it may also involve other dural structures such as the falx and the tentorium (see Ch. 3). In general, leptomeningeal enhancement is most commonly due to infectious meningitis or malignant disease (leptomeningeal metastases), and pachymeningeal enhancement is most commonly due to inflammatory disease, tumor, or intracranial hypotension. However, some infections may cause pachymeningeal enhancement (e.g., tuberculosis, fungal infections, syphilis), and some inflammatory conditions may cause leptomeningeal enhancement (e.g., sarcoidosis). Pachymeningeal enhancement can also be caused by intracranial hypotension, in which case the enhancement is typically smooth and uniform (see Ch. 25).

Potential complications of contrast agents include allergic reactions, contrast-induced nephropathy (with iodinated contrast used with CT), and nephrogenic systemic fibrosis (with gadolinium contrast used with MRI). The latter two complications occur in patients with underlying renal disease, so the risks and benefits of contrast in such patients must be carefully weighed, and contrast is generally contraindicated in patients with renal failure.

CT angiography (CTA) and MR angiography (MRA) allow for visualization of the vasculature (Fig. 2–11). In the neck, brain, and spine, these studies can be used to look for aneurysms and other vascular malformations, arterial stenosis, occlusion, or dissection, and vascular irregularities that may suggest vasculopathy (see Ch. 19). MRA can be performed with contrast or without (time of flight imaging). Since time of flight MRA is dependent on flow velocity, the degree of vascular stenosis may be overestimated with this technique. CTA (which can only be performed using contrast) allows for more accurate measurement of the degree of arterial stenosis than MRA.

CT venography (CTV) and MR venography (MRV) allow for the visualization of the veins and venous sinuses, and are used primarily in the evaluation for venous sinus thrombosis (Ch. 19).

For patients who cannot undergo CTA (e.g., contrast allergy, renal failure) or MRA (e.g., pacemaker), the carotid arteries can be visualized by Doppler ultrasound to assess for carotid artery stenosis (see Ch. 19).

Transcranial Doppler (TCD) ultrasound is used to evaluate the proximal intracranial arteries. It is most commonly used as a screening tool for arterial vasospasm after aneurysmal subarachnoid hemorrhage (see Ch. 19). It can also detect high-intensity transient signals (HITS) that represent emboli passing through the intracranial arteries.

The gold standard for vascular imaging is catheter-based digital subtraction angiography. This technique is used most commonly for the evaluation of aneurysms and other vascular malformations, and in the setting of catheter-based interventions for acute stroke and vascular lesions (Ch. 19).

CT perfusion and MR perfusion are used to study cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT). CBV is the amount of blood in a region of the brain, CBF is the volume of blood moving through a region per unit time, and MTT is the average time for blood to traverse a given region. Perfusion imaging can be used to define the boundaries of tissue that is ischemic but not yet infarcted (ischemic penumbra), which will have decreased CBF and elevated MTT. Sometimes the CBV can actually be normal or increased in such at-risk regions (luxury perfusion).

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) use injections of radioactive substances to evaluate brain metabolism (PET) and brain blood flow (SPECT). Particular patterns of reduced metabolism/blood flow are associated with particular neurodegenerative diseases (e.g., temporoparietal hypometabolism/decreased perfusion in Alzheimer’s disease; temporo-parieto-occipital hypometabolism/decreased perfusion in dementia with Lewy bodies; frontotemporal hypometabolism/decreased perfusion in frontotemporal lobar degeneration, see Ch. 22). PET and SPECT are also used to aid in localization of an epileptic focus in patients undergoing evaluation for epilepsy surgery. Ictal SPECT is used to assess for a focal region of increased blood flow during seizures, and interictal PET evaluates for a focal region of hypometabolism between seizures (Ch. 18).

X-ray, CT, and MRI can all be used to evaluate the spine (Fig. 2–12). MRI is the most sensitive technique for evaluating the spinal cord and nerve roots, but x-ray and CT provide excellent visualization of bony structures. Like brain imaging, interpretation of spine imaging requires identifying normal structures and any abnormalities within them. Vertebrae should be assessed for alignment and fracture, and intervertebral disc spaces should be evaluated for appropriate height or displacement of the intervertebral discs. The spinal cord should be completely surrounded by CSF (bright on T2-weighted images). Loss of this CSF space suggests either compression from outside of the spinal cord (e.g., spondylosis, disc prolapse, epidural hematoma or abscess) or expansion of the cord itself (e.g., due to intramedullary tumor, infection, or inflammation). As with brain MRI, T2-weighted sequences are ideal for evaluating for pathologic hyperintensity in the cord, which could represent tumor, demyelination, infarction, or infection. Contrast administration can aid in identification of abnormalities. The nerve roots should be evaluated for compression (e.g., due to spondylosis or disc prolapse) and enhancement. Nerve root enhancement can occur in inflammatory conditions (e.g., Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, and sarcoidosis) and due to leptomeningeal metastases.

On a midsagittal view of the cervical spine, C2 can be identified as the triangular shape at the top of the vertebral column anterior to the spinal cord, and subsequent cervical vertebrae can be numbered downward from there (Fig. 2–12A). On a midsagittal view of the lumbar spine, S1 can be identified as the first trapezoid-shaped vertebra, and the lumbar vertebrae can be numbered upward from there (Fig. 2–12C).

Lumbar puncture allows for the evaluation of the following parameters in the cerebrospinal fluid (CSF) (Table 2–2):

• 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)

CSF Pressure

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).

CSF Chemistry: Glucose and Protein

CSF Glucose

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.

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.

Increased CSF glucose can be seen when there is serum hyperglycemia.

CSF Protein

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).

CSF Cell Counts and Cell Types

White Blood Cells in the CSF

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).

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).

Red Blood Cells in the CSF

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).

CSF Microbiology: Cultures, PCR, and Antibodies

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).

Patterns of CSF Abnormalities

Several patterns of CSF abnormalities are important to recognize.

Elevated Protein With No or Few Cells (Albuminocytologic Dissociation)

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.)

Elevated WBCs and Protein With Normal Glucose

This is suggestive of a viral process.

Elevated WBCs and Protein With Low Glucose

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.

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).

Traumatic Lumbar Puncture

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).

Additional Tests of CSF

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.

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.

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).

The ratio of amyloid-beta 42 (Aβ-42) to tau is a biomarker for Alzheimer’s disease, discussed further in Chapter 22.