Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Diagnostic Studies


A thorough history and examination should enable you to localize the disease process and generate a differential diagnosis. Confirmation of the diagnosis will usually require neurodiagnostic testing. When any of the tests described here is performed, it is essential to know what you are looking for and to understand the sensitivity (likelihood of a true positive result if the disease is present) and specificity (likelihood of a true negative result if the disease is absent) of each test for diagnosing the disease in question. Risks, benefits, and cost must also be considered.

Lumbar Puncture

Examination of the cerebrospinal fluid (CSF) by lumbar puncture (LP) is essential for diagnosing meningitis and subarachnoid hemorrhage when computed tomography (CT) is negative. It also can be helpful in evaluating peripheral neuropathy, carcinomatous meningitis, pseudotumor cerebri, multiple sclerosis (MS), and a variety of other inflammatory disorders.

  • Technique of LP

    • Proper positioning is the key to success ( Fig. 3.1 ). Position the patient’s back at the edge of the bed, with the head flexed and the legs curled up in the fetal position. Place a pillow under the head; it may be helpful to place another pillow between the legs. Ensure that the shoulders and hips are parallel to each other and perpendicular to the bed (i.e., not tilted forward). Locate the interspace between L4 and L5, which lies at the intercristal line (across the tops of the iliac crests), and insert the needle one level above, between L3 and L4. After sterilizing the area and locally injecting 2% lidocaine, insert a 20-gauge or 22-gauge needle, parallel to the bed and tilted slightly cephalad. As you enter the subarachnoid space, you will feel a slight “pop.” Measure the opening pressure and collect the CSF.

      Fig. 3.1, Positioning for lumbar puncture. A pillow should be placed beneath the head. Hips and shoulders should be parallel to each other and perpendicular to the bed. The spinal needle should be parallel to the bed.

  • Examination of the CSF

    • This examination should always include a cell count (2 mL), protein and glucose analysis (2 mL), a Gram stain and culture (2 mL), and a CSF Venereal Disease Research Laboratory (VDRL) test (1 mL). Additional CSF tests are listed in Table 3.1 . If red blood cells (RBCs) are encountered, check for xanthochromia, which is a yellowish tinge that differentiates true subarachnoid hemorrhage (> 12 hours old) from a traumatic tap. To evaluate the significance of white blood cells (WBCs) in a traumatic tap, recall that the normal ratio of WBCs to RBCs in peripheral blood is 1:700.

      Table 3.1
      Cerebrospinal Fluid Tests

      • Cell count

      • Protein and glucose levels

      • Gram stain and culture

      • VDRL test

      • India ink test (for Cryptococcus neoformans )

      • Wet smear (for fungi and amebae)

      • Stain and culture for AFB (for tuberculosis)

      • Cryptococcal antigen titers

      • pH and lactate levels (abnormal in MELAS)

      • Oligoclonal bands (abnormal in multiple sclerosis)

      • IgG index (intrathecal IgG production)

      • IgG and IgM viral antibody studies

      • Latex agglutination bacterial antigen tests (for pneumococcus, meningococcus, and Haemophilus influenzae )

      • Viral isolation studies

      • Cytology (requires fixation in formalin)

      • Lyme disease antibody titers (compare with serum titers) and Western blot

      • Polymerase chain reaction for Lyme disease, tuberculosis, and causes of viral encephalitis

      • 13-9-9 protein and RT-QuIC (elevated in Creutzfeldt-Jakob disease)

      AFB, Acid-fast bacteria; Ig, immunoglobulin; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke; RT-QuIC, real-time quaking-induced conversion; VDRL, Venereal Disease Research Laboratory.

  • Complications of LP

    • The most frequent complication (in approximately 5% of patients) of LP is spinal headache, which results from persistent leakage of CSF from the entry site, leading to low intracranial pressure (ICP) and traction on the pain-sensitive intracranial dura when the patient is upright. The risk is minimized by using a thin (22-gauge) pencil-tipped spinal needle with a side hole (Sprotte or Gertie Marx), as opposed to a conventional bevel-tipped end hole (Quincke) spinal needle. Other complications are rare and occur only in patients with predisposing conditions: (1) meningitis can result if the needle is passed through infected tissue (e.g., cellulitis) before penetrating the dura; (2) epidural hematoma with compression of the cauda equina can result in patients with coagulopathy; (3) tentorial herniation can result in patients who have space-occupying lesions or severe basilar meningitis; and (4) complete spinal block and cord compression can result in patients who have a partial spinal block. These predisposing conditions are relative (not absolute) contraindications to LP, and the risk/benefit ratio of performing or not performing the procedure must be considered in each case.

Computed Tomography

CT provides “slice” images of the brain by sending axial X-ray beams through the head. The amount of radiation involved is essentially harmless. Tissues are differentiated by the degree to which they attenuate the X-ray beams:

Low attenuation (appears black) Air (darkest)
Fat
Water
Medium attenuation (appears gray) Edematous or infarcted brain
Normal brain
Subacute hemorrhage (3–14 days old)
High attenuation (appears white) Acute hemorrhage
Intravenous contrast material
Bone or metal (brightest)

  • Intravenous contrast

    • When injected, contrast material is normally confined to the cerebral vessels. Hence, contrast enhancement detects the presence of a disrupted blood–brain barrier. Contrast is useful in patients with suspected neoplasm, abscess, vascular malformation, or new-onset seizures.

  • CT perfusion imaging

    • Single or multislice CT perfusion scans are obtained after an intravenous (IV) contrast bolus is injected via an 18-gauge IV. The images must be reconstructed using computerized software. Color-coded maps of cerebral blood flow, cerebral blood volume, and mean transit time can be obtained. The main utility of CT perfusion imaging is to demonstrate a region of noninfarcted hypoperfused brain in patients with acute ischemic stroke or subarachnoid hemorrhage.

  • CT angiography

    • After an IV contrast bolus and computerized image reconstruction, these three-dimensional images can provide good to excellent resolution of the cervical and large proximal intracranial arteries ( Fig. 3.2 ). The main utility of CT angiography is for the diagnosis of extracranial carotid stenosis, proximal intracranial stenoses or occlusions, and saccular intracranial aneurysms. Beware that resolution of the distal vasculature for detecting more subtle lesions such as vasculitic beading, a mycotic aneurysm, or a dural arteriovenous fistula is limited.

      Fig. 3.2, Computed tomography angiogram corresponding to a right middle cerebral artery occlusion

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) provides greater resolution and detail than does CT but takes longer to perform. MRI is superior to CT for evaluating the brain stem and posterior fossa and is superior to myelography for identifying intramedullary spinal cord lesions. Because it uses a powerful magnetic field, there is no exposure to radiation. However, MRI is contraindicated in patients with implanted ferromagnetic objects such as pacemakers, orthopedic pins, and older aneurysm clips.

  • T1 images

    • T1 images (TE [echo time] < 50 ms, TR [repetition time] < 100 ms) are best for showing anatomy. CSF and bone appear black, normal brain appears gray, and fat and subacute blood (> 48 hours old) appears white. Most pathologic processes (e.g., infarction, tumor) are associated with increased water content and hence appear darker than normal brain. Fat suppression T1 images are useful for identifying intramural thrombus (appears white) in cases of cervicocranial arterial dissection.

  • T2 and fluid attenuation inversion recovery (FLAIR) images

    • T2 (TE > 80 ms, TR > 2000 ms) and FLAIR images are best for showing pathology. Most pathologic processes (e.g., infarction, tumor) lead to bright high-signal (white) changes, which reflect increased tissue water content. FLAIR is somewhat more sensitive than T2 in general; the CSF appears dark on FLAIR but bright on T2. Blood on T2 varies in signal intensity according to the age of the hemorrhage, as depicted in Table 3.2 .

      Table 3.2
      Evolution of Appearance of Hemorrhage on Magnetic Resonance Imaging
      Feature T1 Image T2 Image Metabolic Change
      Blood
      4–6 hours No change ◯ Intact RBC with oxyhemoglobin
      7–72 hours No change ● Intact RBC with deoxyhemoglobin
      4–7 days ◯ ● Intact RBC with methemoglobin
      1–4 weeks ◯ ◯ Free methemoglobin
      Months ● ● Hemosiderin with macrophages
      Edema ● ◯ Increased water content
      ● , Low signal, appears dark; ◯ , high signal, appears bright; RBC, red blood cell.

  • Diffusion-weighted imaging

    • Diffusion-weighted imaging (DWI) is useful for detecting hyperacute ischemia in patients with acute stroke. Cerebral ischemia produces an immediate reduction in the diffusion coefficient of water, resulting in high-intensity (white or bright) signal changes on these images within minutes. Over several hours, DWI lesions become associated with high-intensity lesions seen on T2 and FLAIR as the ischemic tissue progresses to infarction. “T2 shine-through” refers to the tendency for high-intensity T2 lesions to produce increased signal on DWI, falsely indicating reduced diffusion.

  • Apparent diffusion coefficient (ADC) maps

    • Compared with DWI, ADC maps are a purer image of restricted diffusion caused by ischemia and cytotoxic edema. ADC maps are mathematically calculated (hence they have lower sharpness and resolution) to have T2 shine-through effects removed. Restricted diffusion caused by ischemia appears black or dark on ADC. A bright region on DWI corresponding with a bright region on ADC is consistent with vasogenic edema.

  • Proton density images

    • Proton density images are partway between T1 and T2 images in signal density. Their main utility is for differentiating periventricular pathology (e.g., white matter demyelination) from CSF.

  • Short tau inversion recovery (STIR) sequences

    • STIR sequences allow summation of T1 and T2 signals and dropout of fat. They are useful for evaluating mesial temporal sclerosis in patients with epilepsy.

  • Flow voids

    • Flow voids appear black on both T1 and T2 images, and they represent high-velocity blood flow (e.g., normal cerebral vessels or arteriovenous malformation [AVM]).

  • Magnetic resonance angiography (MRA)

    • MRA produces images of the extracranial and intracranial cerebral circulation with the brain and skull “subtracted out.” The resolution is adequate for the evaluation of large-scale lesions (e.g., internal carotid artery [ICA] stenosis and large aneurysms) but is inferior to standard angiography for evaluating smaller lesions (e.g., beading, distal spasm). Time-resolved contrast-enhanced MRA offers improved resolution over conventional MRA, particularly for evaluating high-grade stenosis of the cervical arteries.

  • MR venography

    • MR venography provides subtraction images of the major venous sinuses. It can be useful for diagnosing dural sinus thrombosis but is less sensitive than angiography for detecting cortical vein thrombosis.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here

Related Posts