Neurologic Investigations


2	Neurologic Investigations

CEREBROSPINAL FLUID ANALYSIS

Cerebrospinal fluid (CSF) bathes the internal and external surface of the brain and spinal cord. It is produced by the choroid plexus of the ventricles and is absorbed through the villi of the arachnoid granulations that project into the dural venous sinuses. CSF is produced continually at a rate of about 0.5 mL per minute; the total volume is approximately 150 mL. The entire CSF volume is thus replaced about every 5 hours. Lumbar puncture (LP) at the L3–L4 or L4–L5 interspace is the most commonly used means of obtaining CSF for analysis. LP is contraindicated by the presence of a space-occupying lesion that is causing mass effect in the central nervous system (CNS), raised intracranial pressure, local infection or inflammation at the planned puncture site, or a significant coagulopathy.

TECHNIQUE

Optimal positioning is the key to a successful and atraumatic LP. LP is best performed with the patient in the lateral decubitus position with the legs flexed up over the abdomen. Ideally, a pillow should be placed between the legs, and the patient should lie on the edge of the bed where there is better support to keep the back straight. The anterosuperior iliac spine is at the level of the L3–L4 vertebral interspace. The LP may be performed at this level, one interspace higher, or one to two interspaces lower. (Remember that the spinal cord ends at the level of L1–L2.) The needle is inserted with the bevel facing upward, so that it will enter parallel to the ligaments and dura that it pierces rather than cutting them transversely. The needle is directed slightly rostrally to coincide with the downward angulation of the spinous processes. The needle is advanced gently until CSF is obtained. To measure the opening pressure reliably, the patient’s legs should be extended slightly and note should be made of fluctuation of the CSF meniscus within the manometer with respiration.

INTERPRETATION OF RESULTS

CSF is a clear, colorless fluid. The glucose content is about two-thirds that of blood, and it contains up to 40 to 50 mg/dL protein. Fewer than five cells are present, and these are lymphocytes. The opening pressure measured by LP in the lateral recumbent position is about 60 to 150 mm H₂O.

Xanthochromia refers to the yellow discoloration of the supernatant of a spun CSF sample. Its presence helps to distinguish an in vivo intrathecal hemorrhage from a traumatic tap (in which red blood cells [RBCs] have not lysed, so the supernatant is still colorless).

The implications of various CSF findings are summarized in Table 2-1. CSF findings in a variety of common conditions are summarized in Table 2-2. Special tests may be performed as indicated. Some examples include cytology for suspected malignancy, oligoclonal banding for suspected immune-mediated processes such as multiple sclerosis, 14-3-3 protein for Creutzfeldt–Jakob disease, and a variety of polymerase chain reactions and serologic tests to detect infections of the nervous system.

SAFETY, TOLERABILITY, AND COMPLICATIONS

Cerebral or cerebellar herniation may occur when LP is performed in the presence of either a supratentorial or infratentorial mass lesion. A computed tomography (CT) scan should be performed prior to an LP when there are examination findings raising concern for increased intracranial pressure, focal neurologic findings, or severe encephalopathy. Radiologic contraindications to LP include closure of the fourth ventricle and quadrigeminal cistern. Low-pressure headache is the most common complication of LP. It is most effectively prevented by using smaller (higher gauge) LP needles, inserting the bevel of the LP needle parallel rather than perpendicular to the dural fibers, and replacing the stylet after obtaining CSF. Should a post-LP headache develop, it is treated initially by having the patient lie flat and increase his or her intake of liquids and caffeine. In patients who do not respond to these conservative measures, it may be necessary to administer an epidural blood patch (see Chapter 10).

TABLE 2-1. Interpretation of CSF Findings
Red Blood Cells
No xanthochromia	Traumatic tap
Xanthochromia	Subarachnoid hemorrhage; hemorrhagic encephalitis
White Blood Cells
Polymorphs	Bacterial or early viral infection
Lymphocytes	Infection (viral, fungal, mycobacterial); demyelination (MS, ADEM); CNS lymphoma
Elevated protein	Infection (fungal, mycobacterial); demyelination; tumor (e.g., meningioma, meningeal carcinomatosis); sarcoidosis; age
Low glucose	Bacterial infection; mycobacterial infection
Oligoclonal bands	Demyelination (MS); CNS infections (e.g., Lyme disease); noninfectious inflammatory processes (e.g., SLE)
Angiotensin-converting enzyme	May be elevated in neurosarcoidosis
ADEM, acute disseminated encephalomyelitis; CNS, central nervous system; CSF, cerebrospinal fluid; MS, multiple sclerosis; SLE, systemic lupus erythematosus

TABLE 2-2. CSF Findings in Common Neurologic Diseases
Disease	Cells (Pleocytosis)	Protein	Glucose	Other
Bacterial meningitis	Polymorphs	High	Low	Culture and Gram stain may be positive
Viral meningitis/encephalitis	Lymphocytes	High	Normal	Viral PCR may be positive
Tuberculous meningitis	Lymphocytes	High	Very low	Positive for acid-fast bacilli
Guillain–Barré syndrome	None	High (degree depends on interval from symptom onset)	Normal	—
Multiple sclerosis	Several lymphocytes	Slightly high	Normal	OCBs usually present
ADEM	Lymphocytes or polymorphs	Usually high	Normal	OCBs usually absent
Subarachnoid hemorrhage	Lymphocytes and many RBCs	May be high	Normal	Xanthochromia
ADEM, acute disseminated encephalomyelitis; CSF, cerebrospinal fluid; OCB, oligoclonal bands; PCR, polymerase chain reaction; RBC, red blood cell.

KEY POINTS

●A CT scan should be performed prior to LP, especially when there is concern about increased intracranial pressure or focal neurologic abnormalities.

●LP is performed at or below the L2–L3 interspace.

●Xanthochromia indicates recent intrathecal hemorrhage.

COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING

TECHNICAL CONSIDERATIONS

CT measures the degree of X-ray attenuation by tissue. Attenuation is defined simply as the removal (by absorption or scatter) of X-ray photons and is quantified on an arbitrary scale (in Hounsfield units) that is represented in shades of gray. Differences in the shades directly reflect the differences in the X-ray attenuation of different tissues, a property that depends on their atomic number and physical density. Images are usually obtained in either an axial or a coronal plane. Three-dimensional reconstruction and angiography are possible with new-generation spiral CT scanners.

Magnetic resonance imaging (MRI) is similar to CT in that radiant energy is directed at the patient and detected as it emerges from the patient. MRI differs, however, in its use of radiofrequency (RF) pulses rather than X-rays. The images in MRI result from the varying intensity of radio-wave signals emanating from the tissue in which hydrogen ions have been excited by an RF pulse. A detailed understanding of magnetic resonance physics is not necessary for the interpretation of routinely used MRI sequences. It is sufficient to understand that the patient is placed in a magnet and that an RF pulse is administered. Signal intensity is measured at a time interval, known as time to echo (TE), following RF administration. The RF pulse is administered many times in generating an image; the time to repetition (TR) is the time between these RF pulses.

Two basic MRI sequences in common usage are T1-weighted (short TE and TR) and T2-weighted (long TE and long TR) images. Fat is bright on a T1-weighted image, which imparts a brighter signal to the myelin-containing white matter. Water (including CSF) is dark on T1 and bright on T2. T2 images are most useful in evaluating the spinal cord (Fig. 2-1). Gadolinium is the contrast agent used in MRI, and gadolinium-enhanced images are usually acquired with a T1-weighted sequence. Contrast-enhanced images are invaluable in determining the presence of brain tumors, abscesses, other areas of inflammation, and new multiple sclerosis lesions (see Fig. 19-1).

FIGURE 2-1. T2-weighted MRI of the cervical spine. MRI, magnetic resonance imaging.

Other commonly used MRI sequences are fluid-attenuated inversion recovery (FLAIR) and susceptibility- and diffusion-weighted imaging (DWI). FLAIR is a strong T2-weighted image, but one in which the signal from water/CSF has been inverted and is thus of low rather than high intensity. FLAIR is the single best screening image sequence for most pathologic processes of the CNS. It is very useful in assessing the chronic lesion burden in multiple sclerosis (see Fig. 20-2). A susceptibility-weighted sequence is one that is sensitive to the disruptive effect of a substance on the local magnetic field. Examples of substances that exert such a susceptibility effect are calcium, bone, and the blood breakdown products ferritin and hemosiderin. Areas of increased susceptibility appear black on these images.

DWI demonstrates cellular toxicity with high sensitivity and is most commonly employed in the diagnosis of acute stroke, where it can be positive within half an hour of symptom onset. Areas of restricted diffusion appear bright on DWI. Figure 2-2 provides examples of T1, T2, FLAIR, and DWI images.

CLINICAL UTILITY

Head CT is often the initial investigation used in a variety of neurologic disorders, including headache, trauma, seizures, subarachnoid hemorrhage, and stroke. The sensitivity of a CT scan for detecting lesions depends on many factors, including the nature and duration of the underlying disease process. The sensitivity for detecting areas of inflammation, infection, or tumor may be increased by the administration of intravenous contrast. Contrast enhancement indicates local disruption of the blood–brain barrier. CT is the investigation of choice for demonstrating fresh blood.

FIGURE 2-2. Normal T1, T2, FLAIR, and DWI images of the brain. DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery.

Apart from providing better anatomic definition, MRI is particularly useful for imaging the contents of the posterior fossa and craniocervical junction, which are seen poorly on CT because of artifact from surrounding bone. DWI is the most sensitive technique available for demonstrating early tissue ischemia and is therefore extremely useful in the evaluation of patients with suspected stroke.

SAFETY, TOLERABILITY, AND COMPLICATIONS

CT scanning employs X-rays and is thus relatively contraindicated during pregnancy. The use of RF waves in MRI makes this the imaging modality of choice in pregnant women. There is no cross-reactivity between the iodinated contrast agents used in CT and the gadolinium used as a contrast agent in MRI. When contrasted imaging is required, MRI may therefore be preferable when there is a history of allergy to intravenous contrast. Similarly, gadolinium does not have the nephrotoxicity of iodinated contrast. MRI is not safe when metal objects (foreign bodies, plates, and screws) and pacemaker and defibrillator devices are present, unless those materials have been made MRI compatible. Some people with claustrophobia cannot tolerate MRI; under these circumstances, CT is preferred.

KEY POINTS