Overview
Neurologic tests serve to (1) establish a diagnosis when several possible diagnoses exist, (2) help clini-cians make therapeutic decisions, and (3) aid in fol-lowing the results of treatment. In broad terms, neurologic tests can be divided into those that eval-uate function, structure, and molecular/genetic con-cerns. For example, the neurologic examination is the most exquisite test of neurologic function yet devised. While it will provide clues as to the general location of the disease process, it is less reliable than other tests. Cranial magnetic resonance imaging (MRI) and computed tomography (CT) precisely locate abnormal brain tissue but cannot decipher the physiologic consequences of the tissue abnormality.
In this chapter, the major neurologic tests are briefly discussed in terms of their basic principles, indications, cost, and side effects.
These tests are used to (1) divide cognitive abnormalities into specific subtypes that may assist in establishing a diagnosis, (2) determine a quantitative score on specific tests so that repeated tests can measure disease progression or improve-ment, (3) distinguish dementia from psychologic illnesses such as depression, and (4) determine an intelligence quotient (IQ) score for legal or medicosocial reasons. For the usual patient with marked dementia from Alzheimer’s disease, neu-ropsychologic tests add little. One should clearly state the reason for ordering the testing so the neu-ropsychologist can construct the most useful bat-tery of tests to give the patient.
Neuropsychologic tests are safe, inexpensive, and comfortable to the patient. Testing takes 1 to 4 hours depending on the extent of the battery.
These tests can be repeated occasionally but can-not be administered frequently as repeated testing at short intervals would produce a “learning effect” that could falsely improve the score.
Electroencephalogram (EEG)
The EEG is a tracing of electronically amplified and summated electrical activity of the superficial layers of the cerebral cortex adjacent to the calvar-ium. This electrical activity comes primarily from
inhibitory and excitatory postsynaptic potentials of pyramidal cells. Electrodes are placed over the scalp in precise locations to record the brain’s elec-trical activity when awake and often during sleep.
Differences in voltage between 2 selected elec-trodes plotted over time are produced as continu-ous digital waveforms on a computer monitor or as similar analog waveforms on long sheets of paper. The complete EEG tracing is made up of waveforms from several different source elec-trodes. A trained technician performs the EEG and a neurologist interprets the tracing.
Information derived from an EEG is divided into waveforms that suggest epileptiform brain activity and those that suggest an encephalopathy (meta-bolic or structural in origin). Epileptiform brain waves (spikes and sharp waves) are paroxysmal, repetitive, brief, and often of higher voltage than background activity. Background activity is divided into 4 different frequencies (in Hz):β (>12 Hz), α (8–12 Hz),θ (4–7 Hz), and δ (0–3 Hz) that range from fast to slow. The α frequency is the dominant EEG frequency seen in occipital leads when an awake individual has his or her eyes closed.
Most encephalopathies produce slowing of background activity, often into the δ range. EEG electrical activity only comes from intact respond-ing neuronal populations and does not emanate from brain tumors or dead neurons in infarcted brain. However, localized brain masses (tumor or abscess) produce a localized slowing (δ waves) from dysfunctional neurons located around the mass. Some drugs (especially barbiturates) increase background activity into the β range.
While an EEG gives considerable information about abnormal brain function, it provides limited information as to the precise location of the brain dysfunction. Since electrical currents flow by a path of least resistance, the actual source of the electrical activity may not be directly beneath the recording electrode. In general, conventional methods localize the EEG source to a 2-cm cube.
Under some circumstances, the EEG is coupled with a video monitor so the patient’s behavior can be correlated with EEG findings. The EEG is often performed during wakefulness and sleeping as epileptiform discharges are usually more frequent during sleep. The EEG can also study patients dur-ing sleep to evaluate sleep abnormalities, such as narcolepsy. Under special circumstances, elec-trodes can be surgically placed over the cortical 24 FUNDAMENTALS OF NEUROLOGIC DISEASE
Table 3-1 Neuropsychologic Tests and Functions Evaluated
Function Best
Test Evaluated
Weschler Adult Intelligence Intelligence Scale-III and Weschler
Intelligence Scale for Children-III
Weschler Memory Scale Frontal lobe Milan Sorting Test Frontal lobe Porteus Maize Test Frontal lobe Weschler Block Design Parietal lobe Benton Figure Copying Test Parietal lobe Halstead-Reitan Battery (parts) Temporal lobe Milner’s Maze Learning Task Temporal lobe Minnesota Multiphasic Personality Personality
inventory
Rorschach Test Personality
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surface or within the brain to search for specific foci of seizure genesis.
With the advances in CT and MRI, indications for ordering an EEG have diminished. Present indi-cations for ordering a routine EEG include (1) evaluating unwitnessed episodes of loss of con-sciousness for likelihood of seizures, (2) character-izing interictal (between seizures) brain activity to better determine the type of seizure disorder, (3) distinguishing encephalopathy from frequent seizures (status epilepticus) in a stuporous or com-atose patient, (4) distinguishing nonepileptic events from true seizures, and (5) determining brain death.
The routine EEG is safe, inexpensive, and com-fortable to the patient and takes about 2 hours to complete. An EEG can be repeated as often as neces-sary. Figure 3-1 demonstrates typical EEG changes.
Electromyogram (EMG)
The EMG is the evaluation of the electrical function of individual muscle motor unit potentials at rest and during muscle contraction. It is performed by inserting a recording needle electrode into the belly of a muscle. The needle tip is the recording electrode and the needle shaft is the reference electrode in a
concentric needle while a monopolar needle com-pares the fibers’ electrical signal with that of a refer-ence electrode on the skin surface. Electrical activity from muscle fibers is recorded and amplified to appear on an oscilloscope as a tracing of voltages versus time with accompanying sound. Physicians need special training to perform the EMG.
Abnormal motor units or individual muscle fibers demonstrate changes in duration, amplitude, and pattern of the waveform that occur during nee-dle insertion, rest, or voluntary contraction. An EMG distinguishes normal muscle from disease due to nerve damage or muscle disease. An EMG is safe, somewhat uncomfortable to the patient, inex-pensive, and requires 30 to 60 minutes. To mini-mize patient discomfort, the patient should receive a clear description of what will happen and fre-quent reassurance. The following is a description of the types of findings seen on EMG.
NORMAL MUSCLE
Insertion of a needle into a normal muscle injures and mechanically stimulates many muscle fibers, producing a burst of action potentials of short duration (<300 msec). At rest, normal muscle is electrically silent as normal muscle tone is not the
CHAPTER 3—Common Neurologic Tests 25
Figure 3-1 Electroencephalogram typical of seizure.
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result of electrical contraction of muscle fibers. As an electrical impulse travels along the surface of a single muscle fiber toward the recording electrode, the impulse becomes positive (downward deflec-tion by convendeflec-tion) relative to the reference elec-trode. As the impulse comes beneath the electrode, the waveform becomes negative (upward deflec-tion) and then becomes slightly positive and returns to baseline as the impulse travels past the electrode (Figure 3-2). A single muscle fiber con-traction lasts about 2 to 4 milliseconds and is less than 300 µV in amplitude. The firing of a single muscle fiber (called fibrillation, which does not cause visible muscle movement) does not occur normally and is a sign of muscle membrane insta-bility either from denervation or myopathy. In normal muscle, an electrical impulse travels from a spinal cord anterior horn neuron (lower motor neuron) along its axon to eventually innervate 10 to 1,000 muscle fibers (called a motor unit). The number of muscle fibers innervated depends on the muscle, with proximal limb muscles having the highest number of innervated muscle fibers. Dur-ing mild voluntary muscle contraction, an entire motor unit fires almost simultaneously, producing a motor unit action potential (MUAP). A typical MUAP has 3 to 4 excursions across the baseline
(phases) and a maximum amplitude of 0.5 to 5 mV (Figure 3-2). The shape and duration of a given MUAP remain quite constant on repeat fir-ings and generally appear different from other nearby MUAPs.
DENERVATED MUSCLE
Immediately after complete nerve transection, the muscle is paralyzed, unexcitable by nerve stimulation, and electrically silent by EMG except for insertion potentials. Beginning 2 to 3 weeks after a muscle loses its innervation, spon-taneous individual muscle fiber contractions may appear. The EMG demonstrates fibrillations and positive sharp waves (brief monophasic pos-itive spikes). Until the motor unit completely degenerates, spontaneous firing of the MUAP (fasciculation, which produces a visible muscle twitch) also occurs. If the nerve damage is incomplete and occurred several months earlier, the denervated muscle fiber induces adjacent motor nerves to branch or sprout and send a nerve branch to reinnervate the denervated mus-cle fiber (called “sprouting”). MUAPs suggestive of sprouting are of longer duration, contain more phases, and may be of higher maximum amplitude than normal (Figure 3-3c).
MYOPATHY
Death or dysfunction of scattered muscle fibers results in MUAPs during voluntary muscle con-traction that are of shorter duration and lower amplitude than normal (Figure 3-3b). Some MUAPs may be polyphasic from loss of synchro-nous firing. In myositis, there may be accompany-ing fibrillations due to inflammatory damage to adjacent motor nerve endings.
In myopathies that cause myotonia (such as myotonic dystrophy), insertion of the needle pro-duces a train of high-frequency repetitive dis-charges in a positive sharp waveform that diminish in frequency and amplitude over a few seconds.
When heard over a speaker, myotonic discharges sound like a “dive-bomber.”
Nerve Conduction and Neuromuscular Junction Studies
Nerve conduction studies are undertaken to evalu-ate the functioning of motor, autonomic, and sen-sory nerves and neuromuscular junctions. It is 26 FUNDAMENTALS OF NEUROLOGIC DISEASE
Ref.
B C
A A
B
C
-+
2 msFigure 3-2 Electromyogram recording of a single muscle fiber with electrical activity following the dashed arrow.
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possible to determine actual conduction velocities for nerves in the peripheral nervous system, but conduction velocities cannot be determined in the central nervous system. In the CNS, only a nerve
latency time can be obtained because the CNS nerves cannot be stimulated at various points along the nerve pathway. The test is performed by a physician with special training or by a skilled
CHAPTER 3—Common Neurologic Tests 27
Normal
Normal
EMG
Myopathic
Myopathic
Reinnervation Reinnervation
Figure 3-3 Electromyogram (EMG) of motor units in disease.
A
B
C
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technician under a physician’s supervision. The test is safe, inexpensive, mildly uncomfortable for the patient, and takes 1/2to 1 hour.
Indications for ordering nerve studies include (1) determining whether a neuropathy is general-ized or multifocal, (2) determining whether a neu-ropathy is mainly from demyelination or axonal loss, (3) localizing the site of a nerve conduction blockade, and (4) determining and characterizing neuromuscular junction abnormalities. In the common types of distal sensorimotor peripheral neuropathy, nerve studies seldom help establish the etiology.
MOTOR NERVE FUNCTION
Motor nerve conduction velocity studies measure the velocity of the fastest motor nerve axons at var-ious points along a peripheral nerve. Peripheral nerves can be stimulated to fire by application of an electrical impulse to the skin overlying the nerve.
When a muscle contracts, its electrical signal can be detected by placing an electrode on the skin above the muscle belly. The muscle electrical signal is recorded and the time from electrical stimulus to muscle contraction (latency) can be determined and displayed on an oscilloscope. A motor nerve velocity is determined as follows (Figure 3-4). By
moving the stimulating electrode along the nerve pathway, differing latencies (in milliseconds) to muscle contraction are determined. By measuring the distance along the nerve pathway between two exciting stimuli, one can divide the nerve distance (in mm) by the latency difference (in milliseconds) to obtain the nerve velocity (in m/s). Normal motor velocity of the median and ulnar nerves is 50 to 60 m/s and 40–50 m/s in the sciatic nerve. Slowing of the motor nerve velocity may reflect loss of myelin along the nerve (often causing slowing of velocities to 20 to 30 m/s) or loss of the fastest motor nerves (lesser degree of velocity slowing). Slowing of a motor nerve may occur along the entire nerve path-way or at a localized point of nerve compression, such as the ulnar nerve at the elbow.
SENSORY NERVE FUNCTION
Evaluating sensory nerve function is more difficult as the normal signals are weaker and more diffuse following an electrical stimulus because the con-duction velocities of different sensory axons vary considerably. Sensory nerves may be unmyelinated and conduct at 1/2to 2 m/s or be thinly myelinated and conduct at 10 to 20 m/s. The most common sensory nerve test determines the latency time from surface electrical stimulation of the interdigital 28 FUNDAMENTALS OF NEUROLOGIC DISEASE
Reference Site
B (mm) Velocity (m/sec) =
2 (msec) - 1(msec)
A B
Stimulation Site 2 Stimulation
Site 1 Recording
Site Stimulus
1
2 A
B
Figure 3-4 Motor nerve conduction velocity.
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branch of the median nerve to a skin surface elec-trode site over the median nerve just proximal to the wrist. A delayed median nerve sensory latency suggests compression of the nerve at the carpal tunnel.
NEUROMUSCULAR JUNCTION FUNCTION
Information about the function of the neuromuscu-lar junction can be obtained from repetitive nerve stimulation studies. Placement of a skin recording electrode over the belly of a muscle and stimulating the motor nerve produces a compound muscle action potential (CMAP). If the nerve stimulation is repeated, the CMAPs appear identical on the oscillo-scope. In diseases of the neuromuscular junction, the amplitude of the CMAPs may decrease or increase.
In myasthenia gravis and botulism, repetitive nerve stimulation produces a decremental response in the CMAP. The test is safe, inexpensive, somewhat uncomfortable, and takes about 15 minutes.
SENSORY EVOKED POTENTIALS
Occasionally there are indications to evaluate the integrity of central conduction along major sen-sory pathways (visual, auditory, and peripheral sensory system); these are called evoked potentials.
As noted above, actual conduction velocities can-not be obtained, but central modality-specific latencies can. Evoked potential tests record com-puter averages of the EEG that are time locked to repeated (100–500 trials) specific sensory stimuli such as sound, light, or electrical stimulation of the peripheral nerve. The computer averaging reduces background EEG electrical activity to 0 while enhancing the time-locked stimulus signal.
Abnormalities are characterized by a delay for the time-locked signal average to reach its destination or distortions (usually a prolongation of the wave-form and loss of signal amplitude). Sensory evoked potentials are safe, inexpensive, and com-fortable. The major indication is the evaluation of possible diseases that cause central nervous system (CNS) demyelination of these sensory pathways.