Chapter 2: Investigative Studies

INDICATIONS

1. Diagnosis of meningitis, other infective or inflammatory disorders, subarachnoid hemorrhage, hepatic encephalopathy, meningeal malignancies, paraneoplastic disorders, or suspected intracranial pressure abnormalities.

2. Assessment of therapeutic response in meningitis, infective or inflammatory disorders.

3. Administration of intrathecal medications or radiologic contrast media.

4. Rarely, to reduce cerebrospinal fluid (CSF) pressure.

5. In specialized centers, assessment of biomarkers of certain degenerative diseases, especially Creutzfeldt-Jakob disease and Alzheimer disease, and of narcolepsy.

CONTRAINDICATIONS

1. Suspected intracranial mass lesion—Lumbar puncture can hasten incipient transtentorial herniation.

2. Local infection over site of puncture. Use cervical or cisternal puncture instead.

3. Coagulopathy—Correct clotting-factor deficiencies and thrombocytopenia (platelet count below 50,000/μL or rapidly falling) before lumbar puncture to reduce risk of hemorrhage.

4. Suspected spinal cord mass lesion—In this case, remove only a small quantity of CSF to avoid creating a pressure differential above and below the block, which can increase spinal cord compression.

PREPARATION

A. Personnel

With a cooperative patient, one person can perform lumbar puncture. An assistant may be helpful in patient positioning and sample handling especially if the patient is uncooperative or frightened.

B. Equipment and Supplies

The following are usually included in preassembled trays and must be sterile:

1. Gloves

2. Iodine-containing solution for sterilizing the skin

3. Sponges

4. Drapes

5. Lidocaine (1%)

6. Syringe (5 mL)

7. Needles (22- and 25-gauge)

8. Spinal needles (preferably 22-gauge) with stylets

9. Three-way stopcock

10. Manometer

11. Collection tubes

12. Adhesive bandage

C. Positioning

The lateral decubitus position is usually used (Figure 2-1) with the patient lying at the edge of the bed facing away from the clinician. Have the patient maximally flex the lumbar spine to open the intervertebral spaces with the spine parallel to the bed surface and hips and shoulders aligned in the vertical plane.

When a seated position is necessary, have the patient sit on the side of the bed, bent over a pillow on a bedside table, and reach over the bed from the opposite side to perform the procedure.

D. Site of Puncture

Most often, puncture is at the L3-L4 (level of posterior iliac crests) or L4-L5 vertebral interspace because the spinal cord (conus medullaris) terminates just above, approximately at L1-L2, in adults. Thus, with puncture below that level, there is no danger of puncturing the cord.

PROCEDURE

1. For blood and CSF glucose level comparison, draw venous blood for glucose determination. Ideally, obtain simultaneous blood and CSF samples after the patient has fasted for at least 4 hours.

2. Place necessary equipment and supplies in easy reach.

3. Wear a mask and sterile gloves.

4. Apply iodine-containing solution to sponges and wipe a wide area surrounding the interspace. Next, wipe the solution off with clean sponges.

5. Drape the area surrounding the sterile field.

6. Anesthetize the skin overlying the puncture site with lidocaine using a 5-mL syringe and a 25-gauge needle. Next, anesthetize the underlying tissues with lidocaine using a 22-gauge needle.

7. With the stylet in place, insert the spinal needle at the midpoint of the interspace. Keep the needle parallel to the bed surface and angled slightly cephalad, or toward the umbilicus. Keep the needle bevel facing upward toward the face of the person performing the procedure.

8. Advance the needle slowly until feeling a pop from penetration of the ligamentum flavum. Withdraw the stylet to check for flow of CSF through the needle, which indicates entry into the CSF space. If no CSF appears, replace the stylet and advance the needle a short distance, continuing until CSF is present. If the needle cannot be advanced, it is likely that bone is in the way. Withdraw the needle partway, keeping it parallel to the surface of the bed, and advance it again at a slightly different angle.

9. After CSF is obtained, reinsert the stylet. Ask the patient to straighten the legs, and attach the stopcock and manometer to the needle. Turn the stopcock to allow CSF to flow into the manometer, and measure opening pressure. Pressure should fluctuate with the phases of respiration.

10. Turn the stopcock to allow CSF collection and note the appearance (clarity and color) of the fluid. Obtain as much fluid in as many tubes as needed for the tests that have been ordered. Typically, collect 1 to 2 mL in each of five tubes for cell count, glucose and protein determination, measurement of the CSF/serum albumin ratio (test of the blood-brain barrier) and IgG index (to exclude neuroinflammatory disorders), the Venereal Disease Research Laboratory (VDRL) test for syphilis, Gram stain, and cultures. Additional specimens may be collected for other tests, such as cryptococcal antigen, other fungal and bacterial antibody studies, polymerase chain reaction for herpes simplex virus and other viruses, oligoclonal bands (when CNS inflammation is a consideration), glutamine (if hepatic encephalopathy is suspected), biomarkers of Creutzfeldt-Jakob disease (increased 14-3-3 protein level) and Alzheimer disease (low Aβ42 and high total or phosphorylated tau), hypocretin (very low or absent in narcolepsy with cataplexy), and cytologic study. If the CSF appears bloody, obtain additional fluid so that the cell count can be repeated on the specimen in the last tube collected. Cytologic studies require at least 10 mL of CSF.

11. Replace the stopcock and manometer and record closing pressure.

12. Withdraw the needle and apply an adhesive bandage over the puncture site.

13. Previously, patients were instructed to lie prone or supine for 1 or 2 hours after the procedure to reduce the risk of post-lumbar puncture headache. Current evidence suggests this is unnecessary.

COMPLICATIONS

A. Unsuccessful Tap

Several conditions such as marked obesity, degenerative disease of the spine, previous spinal surgery, recent lumbar puncture, and dehydration can make lumbar puncture difficult to perform. When puncture in the lateral decubitus position is impossible, attempt the procedure with the patient in a sitting position. If the tap is again unsuccessful, have an experienced neurologist or neuroradiologist use an oblique approach, image guidance, or perform lateral cervical or cisternal puncture under image guidance.

B. Arterial or Venous Puncture

If the needle enters a blood vessel rather than the spinal subarachnoid space, withdraw the needle and use a new needle to attempt the tap at a different level. In patients with coagulopathy or taking aspirin or anticoagulants, observe carefully for signs of spinal cord compression (see Chapter 9, Motor Disorders) from spinal subdural or epidural hematoma.

C. Post-Lumbar Puncture Headache

After lumbar puncture, patients may have a mild headache that is worse in the upright position but relieved by recumbency. This will usually resolve spontaneously over hours to days. The frequency of this complication is directly related to the size of the spinal needle, but not to the volume of fluid removed. Vigorous hydration or bedrest for 1 or 2 hours after the procedure does not reduce the likelihood of headache. The headache usually responds to nonsteroidal anti-inflammatory drugs (NSAIDs) or caffeine (see Chapter 6, Headache & Facial Pain). Severe and protracted headache can be treated by an autologous blood clot patch, applied by experienced personnel. The use of an atraumatic spinal needle reduces the incidence of post-lumbar puncture headache.

ANALYSIS OF RESULTS

A. Appearance

Note the clarity and color of the CSF as it leaves the spinal needle and any changes in its appearance during the course of the procedure. CSF is normally clear and colorless. It may appear cloudy or turbid with white blood cell counts that exceed approximately 200/μL, but counts as low as about 50/μL may cause light scattering by the suspended cells (Tyndall effect) when the tube is held up to direct sunlight. Color can be imparted to the CSF by hemoglobin (pink), bilirubin (yellow), or rarely, melanin (black).

B. Pressure

With adults in the lateral decubitus position, lumbar CSF pressure is normally between 60 and 180 to 200 mm water. In children, the 90th percentile for opening pressure is 280 mm water. When lumbar puncture is performed with patients seated, they should assume a lateral decubitus posture before CSF pressure is measured. Increased CSF pressure may result from obesity, agitation, or increased intra-abdominal pressure related to position (which may be eliminated by having the patient extend the legs and straighten the back before the opening pressure is recorded). Pathologic conditions associated with the increased CSF pressure include intracranial mass lesions, meningoencephalitis, subarachnoid hemorrhage, and pseudotumor cerebri.

C. Microscopic Examination

This may be undertaken by the person who performed the lumbar puncture or in the clinical laboratory; it always includes a total and differential cell count. Gram stain for bacteria, acid-fast stain for mycobacteria, and cytologic examination for tumor cells may also be indicated. The CSF normally contains up to five mononuclear leukocytes (lymphocytes or monocytes) per microliter, no polymorphonuclear cells, and no erythrocytes unless the lumbar puncture is traumatic. Normal CSF is sterile, so that in the absence of central nervous system (CNS) infection, no organisms are observed with the above stains.

D. Bloody CSF

It is crucial to distinguish between CNS hemorrhage and a traumatic tap. If the blood clears as more fluid is withdrawn, a traumatic tap is likely. This can be confirmed by comparing red cell counts in the first and last tubes of CSF obtained; a marked decrease supports a traumatic tap.

The specimen should also be centrifuged promptly and the supernatant examined. With a traumatic lumbar puncture, the supernatant is colorless. In contrast, after CNS hemorrhage, enzymatic degradation of hemoglobin to bilirubin renders the supernatant yellow (xanthochromic). Xanthochromia may be subtle. Visual inspection requires comparison with a colorless standard (a tube of water) and is best assessed by spectrophotometric quantitation of bilirubin.

Table 2-1 outlines the time course of changes in CSF color after subarachnoid hemorrhage. Blood in the CSF after a traumatic lumbar puncture usually clears within 24 hours and does not clot, whereas after subarachnoid hemorrhage it usually persists for at least 6 days and clotting may occur. Crenation (shriveling) of red blood cells is of no diagnostic value. In addition to breakdown of hemoglobin from red blood cells, other causes of CSF xanthochromia include jaundice with serum bilirubin levels above 4 to 6 mg/dL, CSF protein concentrations exceeding 150 mg/dL, and rarely, the presence of carotene pigments.

White blood cells seen in the CSF early after subarachnoid hemorrhage or with traumatic lumbar puncture result from leakage of circulating whole blood. If the hematocrit and peripheral white blood cell count are within normal limits, there is approximately one white blood cell for every 1,000 red blood cells. If the peripheral white cell count is elevated, this ratio increases proportionately. In addition, for every 1,000 red blood cells present in the CSF, the CSF protein concentration increases by approximately 1 mg/dL.

PROCEDURE NOTES

A note describing the lumbar puncture should be recorded in the patient’s chart and include:

1. Date and time performed.

2. Name of person or persons performing the procedure.

3. Indication.

4. Position of patient.

5. Anesthetic used.

6. Interspace entered.

7. Opening pressure.

8. Appearance of CSF, including changes in appearance during the procedure.

9. Amount of fluid removed.

10. Closing pressure.

11. Tests ordered; for example: Tube 1 (1 mL), cell count; tube 2 (1 mL), glucose and protein levels; tube 3 (1 mL), microbiologic stains; tube 4 (1 mL), bacterial, fungal, and mycobacterial cultures.

12. Results of any studies, such as microbiologic stains, performed by the operator.

13. Complications, if any.

ELECTROENCEPHALOGRAPHY

Electrodes placed on the scalp record the electrical activity of the brain. Electroencephalography (EEG) is easy to perform, relatively inexpensive, and helpful in several different clinical contexts (Figure 2-2).

EVALUATION OF SUSPECTED EPILEPSY

The EEG is useful in evaluating patients with suspected epilepsy. The presence of electrographic seizure activity (abnormal, rhythmic electrocerebral activity of abrupt onset and termination and showing an evolving pattern) during a behavioral disturbance of uncertain nature establishes the diagnosis beyond doubt. It is often not possible to obtain an EEG during a seizure, because these occur unpredictably. However, the EEG may be abnormal interictally (at times when the patient is not experiencing clinical attacks) and is therefore still useful diagnostically. The interictal presence of epileptiform activity (abnormal paroxysmal activity containing some spike discharges) is helpful. Such activity occurs occasionally in patients who have never had a seizure, but its prevalence is greater in patients with epilepsy than in normal subjects. Epileptiform activity in the EEG of a patient with episodic behavioral disturbances that could represent seizures on clinical grounds markedly increases the likelihood that attacks are indeed epileptic, thus supporting the clinical diagnosis.

CLASSIFICATION OF SEIZURE DISORDERS

The EEG findings may help in classifying a seizure disorder and thus in selecting appropriate anticonvulsant medication. For example, in patients with the typical absence of petit mal epilepsy (see Chapter 12, Seizures & Syncope), the EEG is characterized both ictally and interictally by episodic generalized spike-wave activity (see Figure 12-3). By contrast, with episodes of impaired external awareness caused by focal seizures, it may be normal or show focal epileptiform discharges interictally. During seizures, abnormal rhythmic activity of variable frequency may occur with a localized or generalized distribution, but sometimes there are no electrographic correlates. A focal or lateralized epileptogenic source is of particular importance if surgical treatment is under consideration.

ASSESSMENT & PROGNOSIS OF SEIZURES

The EEG may guide prognosis and has been used to follow the course of seizure disorders. A normal EEG implies a more favorable prognosis for seizure control, whereas an abnormal background or profuse epileptiform activity implies a poor prognosis. The EEG findings do not, however, provide a reliable guide to the subsequent development of seizures in patients with head injuries, stroke, or brain tumors. EEG findings are sometimes used to determine whether anticonvulsant medication can be discontinued in patients after a seizure-free interval of several years. Although patients with a normal EEG are more likely to be weaned successfully, such findings provide only a general guide, and patients with a normal EEG can have further seizures after withdrawal of antiepileptic medication. Conversely, no further seizures may occur despite a continuing EEG disturbance.

MANAGEMENT OF STATUS EPILEPTICUS

The EEG is of little help in managing tonic–clonic status epilepticus unless patients have received neuromuscular blocking agents and are in a coma induced by medication. The EEG is then useful in indicating the level of anesthesia and determining whether seizures are continuing. Status is characterized by repeated electrographic seizures or continuous epileptiform (spike-wave) activity. Nonconvulsive status may follow control of convulsive status. In nonconvulsive status epilepticus, the EEG findings provide the only means of making the diagnosis with confidence and in distinguishing the two main types. In absence status epilepticus, continuous spike-wave activity is seen, whereas in focal status, repetitive electrographic seizures are found.

DIAGNOSIS OF OTHER NEUROLOGIC DISORDERS

Certain neurologic disorders produce characteristic but nonspecific EEG abnormalities that help in suggesting, establishing, or supporting the diagnosis. In patients with an acute disturbance of cerebral function, for example, repetitive slow-wave complexes over one or both temporal lobes suggest a diagnosis of herpes simplex encephalitis. Similarly, the presence of periodic complexes in a patient with an acute dementing disorder suggests Creutzfeldt-Jakob disease, subacute sclerosing panencephalitis, or toxicity from lithium, baclofen, or bismuth.

EVALUATION OF ALTERED CONSCIOUSNESS

The EEG slows as consciousness is depressed, depending in part on the underlying etiology. The presence of electrographic seizure activity suggests diagnostic possibilities (eg, nonconvulsive status epilepticus) that might otherwise be overlooked. Serial records permit the prognosis and course to be followed. The EEG response to external stimulation is an important diagnostic and prognostic guide: Electrocerebral responsiveness implies a lighter level of coma. Electrocerebral silence in a technically adequate record implies neocortical death in the absence of hypothermia or drug overdose. In some seemingly comatose patients, consciousness is, in fact, preserved. Although there is quadriplegia and a supranuclear paralysis of the facial and bulbar muscles, the EEG is usually normal and helps in indicating the diagnosis of locked-in syndrome.

MAGNETOENCEPHALOGRAPHY

The magnetic field of electrocerebral activity can be recorded with specialized equipment. The magnetoencephalogram (MEG) is more sensitive than the EEG to activity arising in the cortical sulci, whereas the EEG best detects activity arising at the cortical surface. The MEG has better spatial resolution and can localize activity with more accuracy than the EEG. It is used for localizing abnormal cerebral activity in epilepsy and in localizing the central fissure preoperatively in patients with epilepsy or brain tumors when surgery is planned.

EVOKED POTENTIALS

Noninvasive stimulation of certain afferent pathways elicits spinal or cerebral potentials, which can be used to monitor the functional integrity of these pathways but do not indicate the cause of any lesion involving them. The responses are very small compared with the background EEG activity (noise), which has no relationship to the time of stimulation. The responses to a number of stimuli are therefore recorded and averaged with a computer to eliminate the random noise.

TYPES OF EVOKED POTENTIALS

A. Visual

Monocular visual stimulation with a checkerboard pattern elicits visual evoked potentials, which are recorded from the midoccipital region of the scalp. The most clinically relevant component is the P100 response, a positive peak with a latency of approximately 100 ms. The presence and latency of the response are noted. Although its amplitude can also be measured, alterations in amplitude are far less helpful in recognizing pathology.

B. Auditory

Monaural stimulation with repetitive clicks elicits brainstem auditory evoked potentials, which are recorded at the vertex of the scalp. A series of potentials are evoked in the first 10 ms after the auditory stimulus; these represent the sequential activation of various structures in the subcortical auditory pathway. For clinical purposes, attention is directed at the presence, latency, and interpeak intervals of the first five positive potentials.

C. Somatosensory

Electrical stimulation of a peripheral nerve is used to elicit somatosensory evoked potentials, which are recorded over the scalp and spine. Their configuration and latency depend on the nerve that is stimulated.

INDICATIONS FOR USE

A. Detection of Lesions in Multiple Sclerosis

Evoked potentials can detect and localize lesions in the CNS. This is particularly important in multiple sclerosis, where the diagnosis depends on detecting multifocal CNS lesions. When patients have clinical evidence of only a single lesion, electrophysiologic recognition of abnormalities in other sites helps to establish the diagnosis. When patients with suspected multiple sclerosis present with ill-defined complaints, electrophysiologic abnormalities in the appropriate afferent pathways indicate the organic basis of the symptoms. Although magnetic resonance imaging (MRI) is more useful for detecting lesions, it complements evoked potential studies rather than substituting for them. Evoked potential studies monitor the function rather than anatomic integrity of the afferent pathways and can sometimes reveal abnormalities not detected by MRI (and the reverse also holds true). They also cost less than MRI. In patients with established multiple sclerosis, the evoked potential findings are sometimes used to follow the course of the disorder or its response to treatment, but their value in this regard is unclear.

B. Detection of Lesions in Other CNS Disorders

Evoked potential abnormalities occur in disorders other than multiple sclerosis; multimodal evoked potential abnormalities may be encountered in certain spinocerebellar degenerations, familial spastic paraplegia, Lyme disease, acquired immunodeficiency syndrome (AIDS), neurosyphilis, and vitamin E or B₁₂ deficiency. Their diagnostic value therefore depends on the context in which they are found. Although the findings may permit lesions to be localized within broad areas of the CNS, precise localization may not be possible because the generators of many components are unknown.

C. Assessment and Prognosis After CNS Trauma or Hypoxia

In posttraumatic or postanoxic coma, bilateral absence of cortically generated components of the somatosensory evoked potential implies that cognition will not recover; the prognosis is more optimistic when cortical responses are present on one or both sides. Such studies may be particularly useful in patients with suspected brain death. Somatosensory evoked potentials have also been used to determine the completeness of a traumatic spinal cord lesion; the presence or early return of a response after stimulation of a nerve below the level of the cord injury indicates that the lesion is incomplete and thus suggests a better prognosis than otherwise.

D. Intraoperative Monitoring

The functional integrity of certain neural structures may be monitored by evoked potentials during operative procedures to permit the early recognition of any dysfunction and thereby minimize damage. When the dysfunction relates to a surgical maneuver, it may be possible to prevent or diminish any permanent neurologic deficit by reversing the maneuver.

E. Evaluation of Visual or Auditory Acuity

Visual and auditory acuity may be evaluated by evoked potential studies in patients unable to cooperate with behavioral testing because of age or abnormal mental state.

ELECTROMYOGRAPHY & NERVE CONDUCTION STUDIES

ELECTROMYOGRAPHY

The electrical activity within a discrete region of an accessible muscle can be recorded by inserting a needle electrode into it. The pattern of electrical activity in muscle (electromyogram or EMG) both at rest and during activity has been characterized, and abnormalities have been correlated with disorders at different levels of the motor unit.

A. Activity at Rest

Spontaneous electrical activity is not present in relaxed normal muscle except in the end-plate region where neuromuscular junctions are located, but various types of abnormal activity occur spontaneously in diseased muscle. Fibrillation potentials and positive sharp waves (which reflect muscle fiber irritability) are typically—but not always—found in denervated muscle. They are sometimes also found in myopathic disorders, especially inflammatory disorders such as polymyositis. Although fasciculation potentials, which reflect the spontaneous activation of individual motor units, are occasionally encountered in normal muscle, they are characteristic of neuropathic disorders, especially those with primary involvement of anterior horn cells (eg, amyotrophic lateral sclerosis). Myotonic discharges (high-frequency discharges of potentials from muscle fibers that wax and wane in amplitude and frequency) are found most commonly in disorders such as myotonic dystrophy or myotonia congenita and occasionally in polymyositis or other, rarer disorders. Other types of abnormal spontaneous activity also occur.

B. Activity During Voluntary Muscle Contraction

A slight voluntary contraction of a muscle activates a small number of motor units. The potentials generated by the muscle fibers of individual units within the detection range of the needle electrode can be recorded. Normal motor-unit potentials have clearly defined limits of duration, amplitude, configuration, and firing rates. These limits depend on the muscle under study. In many myopathic disorders, there is an increased incidence of small, short-duration, polyphasic motor units in affected muscles, and an excessive number of units may be activated for a specified degree of voluntary activity. In neuropathic disorders, motor units are lost; the number of units activated during a maximal contraction is therefore reduced, and units fire faster than normal. In addition, the configuration and dimensions of the potentials may be abnormal, depending on the acuteness of the neuropathic process and on whether reinnervation is occurring (Figure 2-3). Variations in the configuration and size of individual motor-unit potentials are characteristic of disorders of neuromuscular transmission.

C. Clinical Utility

Lesions can involve the neural or muscle component of the motor unit, or the neuromuscular junction. When the neural component is affected, the pathologic process can be at the level of the anterior horn cells or at some point along the length of the axon as it traverses a nerve root, limb plexus, and peripheral nerve before branching into its terminal arborizations. Electromyography can detect disorders of the motor units and can indicate the site of the underlying lesion. Neuromuscular disorders can be recognized when clinical examination is unrewarding because the disease is mild or because poor cooperation by the patient or the presence of other symptoms such as pain makes clinical evaluation difficult. The electromyographic findings do not, of themselves, permit an etiologic diagnosis to be reached, and they must be correlated with the clinical findings and the results of other laboratory studies.

The electromyographic findings may provide a guide to prognosis. For example, in an acute disorder of a peripheral or cranial nerve, electromyographic evidence of denervation implies a poorer prognosis for recovery than otherwise.

In contrast to needle electromyography, the clinical utility of surface-recorded electromyography is not established.

NERVE CONDUCTION STUDIES

A. Motor Nerve Conduction Studies

The electrical response of a muscle is recorded to stimulation of its motor nerve at two or more points along its course (Figure 2-4). This permits conduction velocity to be determined in the fastest-conducting motor fibers between the points of stimulation.

B. Sensory Nerve Conduction Studies

The conduction velocity and amplitude of action potentials in sensory fibers can be determined when these fibers are stimulated at one point and their responses are recorded at another point along the course of the nerve.

C. Indications for Use

Nerve conduction studies can confirm the presence and extent of peripheral nerve damage. They are particularly helpful when clinical examination is difficult (eg, in children). Nerve conduction studies are useful in the following contexts:

1. Determining whether sensory symptoms are caused by a lesion proximal or distal to the dorsal root ganglia (in the latter case, sensory conduction studies of the involved fibers will be abnormal) and whether neuromuscular dysfunction is due to peripheral nerve disease.

2. Detecting subclinical involvement of other peripheral nerves in patients with a mononeuropathy.

3. Determining the site of a focal lesion and providing a guide to prognosis in patients with a mononeuropathy.

4. Distinguishing between a polyneuropathy and a mononeuropathy multiplex. This is important because the causes of these conditions differ.

5. Clarifying the extent to which disabilities in patients with polyneuropathy relate to superimposed compressive focal neuropathies, which are common complications.

6. Following the progression of peripheral nerve disorders and their response to treatment.

7. Indicating the predominant pathologic change in peripheral nerve disorders. In demyelinating neuropathies, conduction velocity is often markedly slowed and conduction block may occur; in axonal neuropathies, conduction velocity is usually normal or slowed only mildly, sensory nerve action potentials are small or absent, and electromyography shows evidence of denervation in affected muscles.

8. Detecting subclinical hereditary disorders of the peripheral nerves in genetic and epidemiologic studies.

F-RESPONSE STUDIES

Stimulation of a motor nerve causes impulses to travel antidromically (toward the spinal cord) as well as orthodromically (toward the nerve terminals) and leads a few anterior horn cells to discharge. This produces a small motor response (the F wave) considerably later than the direct muscle response elicited by nerve stimulation. The F wave is sometimes abnormal with lesions of the proximal portions of the peripheral nervous system, such as the nerve roots. F-wave studies may be helpful in detecting abnormalities when conventional nerve conduction studies are normal.

REPETITIVE NERVE STIMULATION

DESCRIPTION

The size of the electrical response of a muscle to supramaximal electrical stimulation of its motor nerve correlates with the number of activated muscle fibers. Neuromuscular transmission is tested by recording (with surface electrodes) the response of a muscle to supramaximal stimulation of its motor nerve either repetitively or by single shocks or trains of shocks at selected intervals after a maximal voluntary contraction.

NORMAL RESPONSE

In normal subjects, little or no change occurs in the size of the compound muscle action potential after repetitive stimulation of a motor nerve at 10 Hz or less or with a single stimulus or a train of stimuli delivered at intervals after a 10-second voluntary muscle contraction. Preceding activity in the junctional region influences the amount of acetylcholine released and thus the size of the end-plate potentials elicited by the stimuli. Although the amount of acetylcholine released is increased briefly after maximal voluntary activity and is then reduced, more acetylcholine is normally released than necessary to bring the motor end-plate potentials to the threshold for generating muscle-fiber action potentials.

RESPONSE IN DISORDERS OF NEUROMUSCULAR TRANSMISSION

A. Myasthenia Gravis

In myasthenia gravis, the reduced release of acetylcholine that follows repetitive firing of the motor neuron prevents compensation for the depleted postsynaptic acetylcholine receptors at the neuromuscular junction. Accordingly, repetitive stimulation, particularly between 2 and 5 Hz, may lead to depressed neuromuscular transmission, with a decrement in the compound muscle action potential recorded from an affected muscle. Similarly, an electrical stimulus of the motor nerve immediately after a 10-second period of maximal voluntary activity may elicit a muscle response that is slightly larger than before, indicating that more muscle fibers are responding. This postactivation facilitation of neuromuscular transmission is followed by a longer depression that is maximal from 2 to 4 minutes after the conditioning period and lasts up to 10 minutes or so. During this period, the compound muscle action potential is reduced in size.

Decrementing responses to repetitive stimulation at 2 to 5 Hz can also occur in congenital myasthenic syndromes.

B. Myasthenic Syndrome and Botulism

In Lambert–Eaton myasthenic syndrome, defective release of acetylcholine at the neuromuscular junction leads to a very small compound muscle action potential elicited by a single stimulus. With repetitive stimulation at rates of up to 10 Hz, the first few responses may decline in size, but subsequent responses increase, and their amplitude is eventually several times larger than the initial response. Patients with botulism exhibit a similar response to repetitive stimulation but the findings are somewhat more variable, and not all muscles are affected. Incremental responses in Lambert–Eaton syndrome and botulism are more conspicuous with high rates of stimulation and may result from the facilitation of acetylcholine release by the progressive accumulation of calcium in the motor nerve terminal.

Autonomic and small-fiber function tests evaluate the control of heart rate, blood pressure, and sweating. Both sympathetic and parasympathetic pathways are assessed. Five simple noninvasive tests of cardiovascular reflexes may be adequate for assessing diabetic (and presumably other) autonomic neuropathies: the heart rate responses to (1) the Valsalva maneuver, (2) standing, and (3) deep breathing; and the blood pressure responses to (4) standing and (5) sustained handgrip. Definite autonomic neuropathy is indicated by an abnormality in two or more tests. Sweating is tested separately. In the thermoregulatory sweat test, the patient is warmed with a radiant heat cradle to increase body temperature by 1°C while the skin is covered with a powder that changes color when moist. This permits the presence and distribution of sweating to be characterized. The sympathetic skin response, that is, the change in voltage at the skin surface following a single electrical stimulus, also can be recorded. This depends on the electrical activity arising from sweat glands and on the reduced electrical resistance of the skin following a noxious stimulus. Quantitative sudomotor axon reflex testing (QSART) assesses postganglionic sympathetic function quantitatively but requires sophisticated and expensive equipment.

DESCRIPTION

The investigation of sleep disorders requires the recording during sleep and wakefulness of multiple physiologic variables, typically the EEG, submental EMG, eye movements, respiratory activity, nasal or oral airflow, oxygen saturation, and the electrocardiogram; a video recording is also made of the patient. Other variables, such as penile tumescence, may be measured depending on the reason for the study.

INDICATIONS FOR USE

1. Diagnosis of sleep-related breathing disorders and their response to various therapeutic maneuvers.

2. Evaluation and diagnosis of patients with suspected narcolepsy. Multiple sleep latency testing is also required, evaluates the time required to fall asleep, and consists of five nap opportunities at 2-hour intervals.

3. Evaluation of periodic limb movements of sleep.

4. Evaluation of insomnia or hypersomnia of uncertain cause.

5. Evaluation of sleep-related symptoms in patients with epilepsy or neuromuscular disorders.

6. Evaluation of organic causes of erectile dysfunction.

COMPUTED TOMOGRAPHY

DESCRIPTION

Computed tomographic (CT) scanning is a noninvasive, computer-assisted, radiologic means of examining anatomic structures (Figure 2-5). It permits the detection of structural intracranial abnormalities with precision, speed, and facility. It is thus of particular use in evaluating patients with progressive neurologic disorders or focal neurologic deficits in whom a structural lesion is suspected, patients with dementia or increased intracranial pressure, and patients with suspected stroke or head injuries. Intravenous administration of an iodinated contrast agent improves the detection and definition of vascular lesions and those associated with a disturbance of the blood–brain barrier. Contrast-enhanced scans may provide more information than unenhanced scans in patients with known or suspected primary or secondary brain tumors, arteriovenous malformations (AVMs), aneurysms, cerebral abscesses, chronic isodense subdural hematomas, or infarctions. Because the contrast agents may affect the kidneys adversely, they should be used with discrimination. Other adverse effects of the contrast agents in common use are pain, nausea, thermal sensations, and anaphylactoid reactions that include bronchospasm and death.

INDICATIONS FOR USE

A. Stroke

CT scan can distinguish infarction from intracranial hemorrhage; it is particularly sensitive in detecting intracerebral hematomas (see Figure 13-20), the location of which may provide a guide to their cause. CT scan occasionally demonstrates a nonvascular cause of the patient’s clinical deficit, such as a tumor or abscess.

B. Tumor

CT scans can indicate the site of a brain tumor, the extent of any surrounding edema, whether the lesion is cystic or solid, and whether it has displaced midline or other normal anatomic structures. It also demonstrates any acute hemorrhagic component.

C. Trauma

CT scans are important for detecting traumatic intracranial (epidural, subdural, subarachnoid, or intracerebral) hemorrhage and bony injuries. They also provide a more precise delineation of associated fractures than do plain x-rays.

D. Dementia

CT scanning may indicate the presence of a tumor or hydrocephalus (enlarged ventricles), with or without accompanying cerebral atrophy. The occurrence of hydrocephalus without cerebral atrophy in demented patients suggests normal pressure or communicating hydrocephalus. Cerebral atrophy can occur in demented or normal elderly subjects.

E. Subarachnoid Hemorrhage

In patients with subarachnoid hemorrhage, the CT scan generally indicates the presence of blood in the subarachnoid space and may even suggest the source of the bleeding (see Figure 6-5). If the CT scan findings are normal despite clinical findings suggestive of subarachnoid hemorrhage, the CSF should be examined to exclude hemorrhage or meningitis. CT angiography (see later) may demonstrate an underlying vascular malformation or aneurysm.

MAGNETIC RESONANCE IMAGING

DESCRIPTION

Magnetic resonance imaging (MRI) involves no ionizing radiation. The patient lies within a large magnet that aligns some of the protons in the body along the magnet’s axis. The protons resonate when stimulated with radiofrequency energy, producing a tiny echo that is strong enough to be detected. The position and intensity of these radiofrequency emissions are recorded and mapped by a computer. The signal intensity depends on the concentration of mobile hydrogen nuclei (or nuclear-spin density) of the tissues. Spin–lattice (T1) and spin–spin (T2) relaxation times are mainly responsible for the relative differences in signal intensity of the various soft tissues; these parameters are sensitive to the state of water in biologic tissues. Pulse sequences with varying dependence on T1 and T2 selectively alter the contrast between soft tissues (Figure 2-6).

The soft-tissue contrast available with MRI makes it more sensitive than CT scanning in detecting certain structural lesions. MRI provides better contrast than CT scans between the gray and white matter of the brain. It is superior for visualizing abnormalities in the posterior fossa and spinal cord, for subacute and chronic hemorrhage, and for detecting lesions associated with multiple sclerosis or those that cause seizures. In addition to its greater sensitivity, it is also free of bony artifact and permits multiplanar (axial, sagittal, and coronal) imaging with no need to manipulate the position of the patient. Because there are no known hazardous effects, MRI studies can be repeated in a serial manner if necessary. Occasional patients cannot tolerate the procedure without sedation because of claustrophobia.

Gadopentetate dimeglumine (gadolinium-DPTA) is an effective enhancing MRI contrast agent that is stable and well-tolerated intravenously. It is useful in identifying small tumors that, because of their similar relaxation times to normal cerebral tissue, may be missed on unenhanced MRI. It also helps to separate tumor from surrounding edema, identify leptomeningeal disease, and provide information about the blood–brain barrier. Gadolinium has been associated with nephrogenic systemic fibrosis in patients with renal insufficiency, so it should be used judiciously in this setting.

INDICATIONS FOR USE & COMPARISON WITH CT SCAN

A. Stroke

Within a few hours of vascular occlusion, cerebral infarcts may be detected by MRI. Breakdown in the blood–brain barrier (several hours after onset of cerebral ischemia) permits the intravascular content to be extravasated into the extracellular space. This can be detected by T2-weighted imaging and fluid-attenuated inversion-recovery (FLAIR) sequences. Diffusion-weighted MRI also has an important role in the early assessment of stroke, as is discussed later, whereas CT scans may be unrevealing for up to 48 hours. Thereafter, the advantage of MRI over CT scanning lessens, except that MRI detects smaller lesions and provides superior imaging of the posterior fossa.

Nevertheless, to determine quickly whether hemorrhage has occurred, CT scanning without contrast is usually the preferred initial study in acute stroke. Hematomas of more than 2 to 3 days’ duration, however, are better visualized by MRI. Although MRI can detect and localize vascular malformations, angiography is necessary to define their anatomic features and plan effective treatment. In cases of unexplained hematoma, a follow-up MRI obtained 3 months later may reveal the underlying cause, which is sometimes unmasked as the hematoma resolves.

B. Tumor

Both CT scans and MRI are useful in detecting brain tumors. MRI is the preferred technique because of its greater soft tissue sensitivity, the absence of bone artifacts at the vertex or in the posterior fossa, and the ability to employ advanced imaging techniques such as MR spectroscopy and diffusion and perfusion imaging that better characterize a lesion. MRI or CT scan may detect secondary effects of tumors, such as cerebral herniation, but MRI provides more detailed and sensitive anatomic information. Neither technique, however, permits the type of a tumor to be determined with certainty.

C. Trauma

In the acute phase after head injury, CT scan is preferable to MRI because it requires less time, is superior for detecting intracranial hemorrhage, and may reveal bony injuries. Similarly, spinal MRI should not be used in the initial evaluation of patients with spinal injuries because nondisplaced fractures are often not visualized. For follow-up purposes, however, MRI is helpful for detecting parenchymal pathology of the brain or spinal cord.

D. Dementia

In patients with dementia, either CT scan or MRI can help in demonstrating treatable structural causes, but MRI is more sensitive in demonstrating abnormal white matter signal and associated atrophy.

E. Multiple Sclerosis

Lesions in the cerebral white matter or the cervical cord are best detected by MRI, as lesions may not be visualized on CT scans. The lesions on MRI may have signal characteristics resembling those of ischemic changes, however, and clinical correlation is therefore always necessary. Gadolinium-enhanced MRI permits lesions of different ages to be distinguished. This ability facilitates the diagnosis of multiple sclerosis: The presence of lesions of different ages suggests a multiphasic disease, whereas lesions of similar age suggest a monophasic disorder, such as acute disseminated encephalomyelitis.

F. Infections

MRI is sensitive in detecting white matter edema and probably permits earlier recognition of focal areas of cerebritis and abscess formation than CT scan. Diffusion MR imaging is particularly helpful in detecting areas of reduced diffusion, typical of purulent abscess and encephalitis.

CONTRAINDICATIONS

MRI is contraindicated by the presence of intracranial ferromagnetic aneurysm clips, metallic foreign bodies in the eye, demand-mode pacemakers, and cochlear implants. Many implanted devices are also contraindications for MRI. Patients requiring close monitoring are probably best studied by CT if possible. Furthermore, MRI is difficult in patients with claustrophobia, extreme obesity, uncontrolled movement disorders, or respiratory disorders that require assisted ventilation or carry any risk of apnea. Advances in MRI-compatible mechanical ventilators, pacemakers, and monitoring equipment, however, now allow many critically ill patients to be scanned safely.

DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING

This technique, in which contrast within the image is based on the microscopic motion of water protons in tissue, provides information that is not available on standard MRI or CT. It is particularly important in the assessment of stroke because it can discriminate cytotoxic edema (which occurs in strokes) from vasogenic edema (found with other types of cerebral lesion) and thus reveals cerebral ischemia early and with high specificity. Diffusion-weighted MRI permits reliable identification of acute cerebral ischemia during the first few hours after onset, before it is detectable on standard MRI. This is important because it reveals the true volume of infarcts prior to treatment with thrombolytic agents. However, because diffusion-weighted imaging will be positive in the setting of cytotoxic edema of any cause (eg, brain abscess, highly cellular tumors), clinical correlation is always required. When more than one infarct is found on routine MRI, diffusion-weighted imaging permits the discrimination of acute from older infarcts by the relative increase in signal intensity of the former.

DIFFUSION TENSOR MAGNETIC RESONANCE IMAGING

This technique produces neural tract images by measuring the diffusion of water in tissue. It is important in determining the severity and extent of cerebral involvement after head injury, localizing brain tumors, and planning surgical procedures. White matter changes may be detected that are not seen on conventional MRI.

PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING

Blood flow through the brain may be measured using either an injected contrast medium (eg, gadolinium) or an endogenous technique (in which the patient’s own blood provides the contrast). Cerebral blood-flow abnormalities can be recognized and the early reperfusion of tissues after treatment can be confirmed. Cerebral ischemia may be detected very soon after clinical onset. Comparison of the findings from diffusion-weighted and perfusion-weighted MRI may have a prognostic role and is currently under study. The distinction of reversible from irreversible ischemic damage is important in this regard. Perfusion-weighted imaging also contributes in distinguishing between various types of brain tumors such as gliomas and metastases.

POSITRON EMISSION TOMOGRAPHY

Positron emission tomography (PET) is an imaging technique that uses positron-emitting radiopharmaceuticals, such as ¹⁸F-fluoro-2-deoxy-D-glucose or ¹⁸F-L-dopa, to map brain biochemistry and physiology. PET thus complements other imaging methods that provide primarily anatomic information, such as CT scan and MRI, and may demonstrate functional brain abnormalities before structural abnormalities are detectable. PET has proved useful in several clinical settings and is now combined with CT or MR scanners in hybrid machines. When patients with medically refractory epilepsy are being considered for surgical treatment, PET CT scan can identify focal areas of hypometabolism in the temporal lobe as likely sites of the origin of seizures. PET can also be useful in the differential diagnosis of dementia, because common dementing disorders such as Alzheimer disease and frontotemporal dementia exhibit different patterns of abnormal cerebral metabolism. In vivo imaging of amyloid-β (Aβ) with PET facilitates the early diagnosis of Alzheimer disease and provides prognostic information for patients with mild cognitive impairment. PET can help distinguish between clinically similar movement disorders, such as Parkinson disease and progressive supranuclear palsy, and can provide confirmatory evidence of early Huntington disease. It may also be of value in grading gliomas, selecting tumor biopsy sites, and distinguishing recurrent tumors from radiation-induced brain necrosis. It has been an important tool with which to investigate the functional involvement of different cerebral areas in behavioral and cognitive tasks and is used frequently in patients with suspected metastatic disease. However, PET is more expensive than MR or CT alone, requires administration of radioactive isotopes, and thus exposes subjects to radiation.

SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY

In single-photon emission computed tomography (SPECT), chemicals containing isotopes that emit single photons are administered intravenously or by inhalation to image the brain. SPECT has been used, in particular, to measure perfusion, to investigate receptor distribution, and to detect areas of increased metabolism such as occurs with seizures.

A specific contrast agent (¹²³I ioflupane) used with SPECT detects dopamine transporters (DaT) and helps to distinguish parkinsonian syndromes from essential tremor when this is clinically difficult. A DaT scan is also used to confirm a diagnosis of Parkinson disease in patients with ambiguous symptoms.

FUNCTIONAL MAGNETIC RESONANCE IMAGING

Functional MRI (fMRI) involves pulse sequences that change in signal intensity in response to alterations in the oxygen concentration of venous blood (blood oxygen level–dependent [BOLD]-fMRI), which correlate with focal cerebral activity. Studies are performed with the subject at rest and then after an activation procedure so that the change in signal intensity reflects the effect of the activation procedure on local cerebral blood flow (Figure 2-7). Studies are also performed without a stimulus (“resting state fMRI”) to interrogate the brain’s functional organization. fMRI studies are indicated for preoperative functional mapping of sensorimotor and language areas in the evaluation of patients with brain tumors, as well as in some cases of epilepsy or vascular malformations.

MAGNETIC RESONANCE SPECTROSCOPY

Magnetic resonance spectroscopy provides information about the chemical composition of tissue. Proton magnetic resonance spectroscopy (¹H-MRS) can determine levels of N-acetylaspartate (exclusive to neurons) or choline, creatinine, and lactate (glia and neurons). Measurements of brain concentrations of these metabolites may be useful in detecting specific tissue loss in Alzheimer disease or other neurodegenerative disorders; in distinguishing brain tumors from non-neoplastic lesions such as abscesses and in classifying brain tumors; in identifying certain inborn errors of metabolism and leukodystrophies; in prognostication of hypoxic-ischemic brain injury; and in localizing the source of seizures in temporal lobe epilepsy. Phosphorus magnetic resonance spectroscopy (³¹P-MRS) may be useful in the evaluation of metabolic muscle diseases.

ARTERIOGRAPHY

DESCRIPTION

The intracranial circulation is visualized most satisfactorily by arteriography, in which the major vessels to the head are opacified and radiographed after injection of contrast material through an arterial or venous catheter. Specifically, a catheter is introduced into the femoral or brachial artery and passed into one of the major cervical vessels. A radiopaque contrast material is then injected through the catheter, allowing the vessel (or its origin) to be visualized. Access to the cranial vessels with a catheter also allows for the delivery of certain therapies. The technique, generally performed after noninvasive imaging by CT scan or MRI, has a definite (approximately 1%) morbidity and mortality associated with it and involves considerable exposure to radiation. It is contraindicated in patients who are allergic to the contrast medium. Stroke may result as a complication of arteriography. Moreover, after the procedure, bleeding may occur at the puncture site, and the catheterized artery (usually the femoral artery) may become occluded, leading to distal ischemic complications. The puncture site and the distal circulation must therefore be monitored.

INDICATIONS FOR USE

The major indications for cerebral arteriography are:

1. Diagnosis of intracranial aneurysms, arteriovenous malformations (AVMs), or fistulas. Although these lesions can be visualized by CT scan or MRI, their detailed anatomy and the vessels that feed, drain, or are otherwise implicated in them cannot reliably be defined by these other means. Moreover, arteriography is required for interventional procedures such as embolization, the injection of occlusive polymers, or the placement of detachable balloons or coils to treat certain vascular anomalies.

2. Detection and definition of the underlying lesion in patients with subarachnoid hemorrhage who are considered good operative candidates (see Chapter 6, Headache & Facial Pain).

3. Detection and management of vasospasm after subarachnoid hemorrhage.

4. Emergency embolectomy in the setting of ischemic stroke due to large-vessel occlusion. In addition, arteriography can define vascular lesions in patients with transient cerebral ischemic attacks or strokes if surgical treatment such as carotid endarterectomy is being considered.

5. Evaluation of small vessels, when vasculitis is under consideration.

6. Diagnosis of cerebral venous sinus thrombosis.

7. Evaluation of space-occupying intracranial lesions, particularly when CT scanning or MRI is unavailable. There may be displacement of the normal vasculature, and in some tumors neovasculature may produce a blush or stain on the angiogram. Meningiomas are supplied from the external carotid circulation. Presurgical embolization of certain tumors reduces their blood supply and decreases the risk of major bleeding during resection.

MAGNETIC RESONANCE ANGIOGRAPHY

Several imaging techniques to visualize blood vessels by MRI depend on the physical properties of flowing blood, thereby allowing visualization of vasculature without the use of intravenous contrast. These properties include the rate at which blood is supplied to the imaged area, its velocity and relaxation time, and the absence of turbulent flow. Magnetic resonance (MR) angiography is a noninvasive technique that is cheaper and less risky than conventional angiography. It has been most useful in visualizing the carotid arteries and proximal portions of the intracranial circulation, where flow is relatively fast. The images are used to screen for stenosis or occlusion of vessels and for large atheromatous lesions. It has particular utility in screening for venous sinus occlusion. Resolution is inferior to that of conventional angiography, and occlusive disease may not be recognized in vessels with slow flow. Moreover, intracranial MR angiograms may be marred by saturation or susceptibility artifacts that result in irregular or discontinuous signal intensity in vessels close to bone. Although current techniques allow visualization of AVMs and aneurysms greater than 3 mm in diameter, conventional angiography remains the “gold standard.” Finally, MR angiography may reveal dissection of major vessels: Narrowing is produced by the dissection, and cross-sectional images reveal the false lumen as a crescent of abnormal signal intensity next to the vascular flow void.

CT ANGIOGRAPHY

CT angiography is a minimally invasive procedure that requires a CT scanner capable of acquiring numerous thin, overlapping sections quickly after intravenous injection of a bolus of contrast material. Because the images are acquired within a matter of 5 to 10 seconds, CTA is less likely to be affected by patient movement than MR angiography. A wide range of vessels can be imaged with the technique.

CT angiography of the carotid bifurcation is being used increasingly in patients with suspected disease of the carotid arteries. It can also be used for intracranial imaging and can detect stenotic or aneurysmal lesions. However, sensitivity is reduced for aneurysms less than 3 mm, and the method cannot adequately define aneurysmal morphology in the preoperative evaluation of patients. It is sensitive in visualizing the anatomy in the circle of Willis, the vasculature of the anterior and posterior circulations, and intracranial vasoocclusive lesions, but it may not reveal plaque ulceration or disease of small vessels. It is a reliable alternative to MR angiography, but both techniques are less sensitive than conventional angiography.

In patients with acute stroke, CT angiography provides important information complementary to conventional CT scan studies, revealing the site and length of vascular occlusion and the contrast-enhanced arteries distal to the occlusion as a reflection of collateral blood flow. CT perfusion, in which the relative blood flow to an area of the brain is measured as iodinated contrast passes through over time, can provide additional information regarding the proportion of ischemic to infarcted tissue in this setting.

PLAIN X-RAYS

Plain x-rays of the spine can reveal congenital, traumatic, degenerative, or neoplastic bony abnormalities or narrowing (stenosis) of the spinal canal. Degenerative changes become increasingly common with advancing age, and their clinical relevance depends on the context in which they are found.

MYELOGRAPHY

Injecting iodinated contrast medium into the subarachnoid space permits visualization of part or all of the spinal subarachnoid system. The cord and nerve roots, which are silhouetted by the contrast material, are visualized indirectly. CSF leaks can be documented and localized. The procedure is relatively safe but carries the risk of headache, vasovagal reactions, persistent CSF leak, nausea, and vomiting. Rarely, confusion and seizures occur. Other rare complications include traumatically induced herniated intervertebral disks due to poor technique and damage to nerve roots.

The contrast agent is absorbed from the CSF and is excreted by the kidneys; approximately 75% is eliminated over the first 24 hours. While current water soluble agents do not cause arachnoiditis, tonic–clonic seizures have sometimes occurred when large amounts of contrast enter the intracranial cavity. Contrast myelography may be followed by a CT scan of the spine while the medium is still in place. This shows the soft tissue structures in or about the spinal cord and provides information complementary to that obtained by the myelogram (see later).

Myelography has largely been replaced by MRI and CT scanning but it is still sometimes performed, particularly in patients with spinal hardware precluding useful MRI studies and in those with suspected CSF fistula.

COMPUTED TOMOGRAPHY

CT scanning after myelography has become a routine procedure and is particularly helpful when the myelogram either fails to reveal any abnormality or provides poor visualization of the area of interest. The myelogram may be normal, for example, when there is a laterally placed disk protrusion; in such circumstances, a contrast-enhanced CT scan may reveal the lesion. It is also useful in visualizing more fully the area above or below an almost complete block in the subarachnoid space and in providing further information in patients with cord tumors.

CT scan is most helpful in defining the bony anatomy of the spine. It is performed routinely after trauma to exclude cervical spine fractures when spinal injury cannot be excluded on clinical grounds. CT scanning may show osteophytic narrowing of neural foramina or the spinal canal in patients with cervical spondylosis and may show spinal stenosis or disk protrusions in patients with neurogenic claudication. In patients with neurologic deficits, however, MRI is generally preferred because it provides more useful information about the spinal canal, neural foramina, and spinal cord.

MAGNETIC RESONANCE IMAGING

Spinal MRI is the best method for visualizing the spinal canal and its contents, and—in most cases—it provides the information obtained previously by myelography. Imaging of the spinal canal by MRI is direct and noninvasive.

Spinal MRI is indicated in the urgent evaluation of patients with suspected spinal cord compression. It permits differentiation of solid from cystic intramedullary lesions. MRI is the preferred imaging method for visualizing cord cavitation and detecting any associated abnormalities at the craniocervical junction. Congenital abnormalities associated with spinal dysraphism are also easily visualized by MRI. In patients with degenerative disk disease, MRI is an important means of detecting cord or root compression (Figure 2-8). However, abnormal MRI findings in the lumbar and cervical spine are common in asymptomatic subjects, especially in middle or later life, and care must therefore be exercised in attributing symptoms such as back pain to anatomic abnormalities that may be coincidental. When a spinal AVM (dural fistula) is suspected but MRI is unrevealing, a myelogram is sometimes helpful, but spinal angiography is often undertaken without proceeding to myelography.

MRI and ultrasound imaging of peripheral nerves may provide complementary information to clinical examination and electrodiagnostic studies, for example in nerve entrapment syndromes or after nerve injury, but the clinical role of these imaging studies is still being defined. MRI measures of muscle volume and composition and of edema are also being studied, as is their clinical application in patients with muscle disease. Muscle ultrasound is helpful in the identification of specific muscles for chemodenervation procedures, and its role in other clinical contexts is under study.

In 2D (B-mode) ultrasonography, echoes reflected from anatomic structures are plotted on an oscilloscope screen in two dimensions. The resulting brightness at each point reflects the density of the imaged structure. The technique has been used to image the carotid artery and its bifurcation in the neck, permitting evaluation of the extent of extracranial vascular disease. Blood flowing within an artery does not reflect sound, and the lumen of the vessels therefore appears black. The arterial wall can be seen, however, and atherosclerotic lesions can be detected. Note that with severe stenosis or complete occlusion of the internal carotid artery, it may not be possible to visualize the carotid artery bifurcation.

The velocity of blood flow through an artery can be measured by Doppler ultrasonography. Sound waves within a certain frequency range are reflected off red blood cells, and the frequency of the echo provides a guide to the velocity of the flow. Any shift in frequency is proportional to the velocity of the red cells and the angle of the beam of sound waves. When the arterial lumen is narrowed, the velocity of flow increases; increased frequencies are therefore recorded by Doppler ultrasonography. Spectral analysis of Doppler frequencies is also used to evaluate the anatomic status of the carotid artery.

Transcranial Doppler studies can be used to detect intracranial arterial lesions or vasospasm (eg, after subarachnoid hemorrhage) and to assess the hemodynamic consequences of extracranial disease of the carotid arteries.

Duplex instruments perform a combination of both B-mode imaging and Doppler ultrasonography, thereby simultaneously providing information about the structure and the hemodynamics of the circulation in a color-coded format. The technique is commonly used to screen asymptomatic patients at high risk of carotid artery disease. Depending on the quality of the study, a CT angiogram may be necessary to confirm the extent and severity of disease. Symptomatic patients with suspected atheromatous lesions of the cervical carotid artery are best studied by magnetic resonance or computed tomographic angiography to determine whether carotid endarterectomy is indicated. Duplex ultrasound is also useful for follow–up after carotid endarterectomy or stenting to detect recurrent stenosis. The role of ultrasonography in neuromuscular disease, referred to earlier, is currently under study.

BRAIN BIOPSY

Biopsy of brain tissue is sometimes useful when less invasive methods, such as imaging studies, fail to provide a diagnosis. Brain lesions most amenable to biopsy are those that can be localized by imaging studies; are situated in superficial, surgically accessible sites; and do not involve critical brain regions, such as the brainstem or the areas of cerebral cortex involved in language or motor function. Cerebral disorders that can be diagnosed by biopsy include primary and metastatic brain tumors, inflammatory conditions such as vasculitis or sarcoidosis, infectious disorders such as brain abscess, and certain degenerative diseases such as Creutzfeldt-Jakob disease, although MRI has largely supplanted biopsy in the diagnosis of this disorder.

MUSCLE BIOPSY

Histopathologic examination of a biopsy specimen of a weak muscle can indicate whether the weakness is neurogenic or myopathic. In neurogenic disorders, atrophied fibers occur in groups, adjacent to groups of larger uninvolved fibers. In myopathies, atrophy occurs in a random pattern; the nuclei of muscle cells may be centrally situated, rather than in their normal peripheral location; and fibrosis or fatty infiltration may also be found. Examination of a muscle biopsy specimen may also permit certain inflammatory diseases of muscle, such as polymyositis, to be recognized and treated.

In some patients with a suspected myopathy, although the electromyographic findings are normal, examination of a muscle biopsy specimen reveals the nature of the underlying disorder. Conversely, electromyographic abnormalities suggestive of a myopathy are sometimes found in patients in whom the histologic or histochemical studies fail to establish a diagnosis of myopathy. The two approaches are therefore complementary.

NERVE BIOPSY

Nerve biopsy is not required to establish a diagnosis of peripheral neuropathy. The nature of any neuropathologic abnormalities, however, can sometimes suggest the underlying cause, such as a metabolic storage disease (eg, Fabry disease, Tangier disease), infection (eg, leprosy), inflammatory change, vasculitis, or neoplastic involvement. The findings are not always of diagnostic relevance, and nerve biopsy itself can be performed only on accessible nerves. It is rarely undertaken on more than a single occasion.

ARTERY BIOPSY

In patients with suspected giant cell arteritis, temporal artery biopsy may help to confirm the diagnosis, but the pathologic abnormalities are usually patchy in distribution. Therefore, a normal study should not exclude the diagnosis or lead to withdrawal of treatment.

SKIN BIOPSY

In patients with suspected small-fiber neuropathy, punch skin biopsy may be performed to determine the number, density, and length of small nerve fibers in the epidermis. The most common biopsy site is the lateral calf, for which normative values have been established.