4.3 Electrophysiologic Studies
4.4 Ultrasonography (Neurosonography)
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The patient, a 72-year-old woman who worked at the checkout counter in a family-owned grocery store, consulted her family physician in January 2001 because of a reduction of sensation in her left thumb, index finger, and middle finger. The doctor suspected carpal tunnel syndrome and prescribed a volar hand splint to be worn at night.
The splint did not help much, and the patient wore it only irregularly. Electroneurography (ENG) 2 years later revealed normal sensory nerve conduction velocities and a normal distal motor latency in the median nerve. By this time, the sensory disturbance had spread to include the fourth and fifth fingers of the left hand as well. The left biceps reflex was weak, but all other proprioceptive reflexes in the upper limb were normal. The family physician recommended that she try wearing the splint more consistently. As time went on, the patient noticed weakness of the left hand. She began dropping things involuntarily out of the left hand and, a few months later, she consulted a neurologist. She now had paresthesiae in the first through third digits of the right hand as well.
The most common cause of a sensory disturbance in the hands is carpal tunnel syndrome, a compressive neuropathy of the median nerve under the transverse carpal ligament. The clinical diagnosis is confirmed by ENG: typically, the sensory nerve conduction velocity across the carpal canal is low, or the distal motor latency of the median nerve is prolonged. The normal ENG findings in this patient should have led her doctor to suspect a C6 radiculopathy, particularly in view of the weak biceps reflex. Nothing more was done, however, and she only presented to a neurologist when the strength of the hand was affected.
The neurologist’s examination revealed spastic quadriparesis, more pronounced in the upper limbs, particularly the left hand. The biceps and triceps reflexes were not elicitable on the left, but all other reflexes in the upper and lower limbs were very brisk. Babinski signs were present bilaterally. Pain and temperature sensation were markedly diminished from C6 downward, with a lesser diminution of touch and position sense. There was no sensation whatever in the C7 and C8 segments. These findings pointed to a central spinal cord lesion; the slow progression of symptoms (years) suggested syringomyelia or a spinal cord tumor as the most likely elements in the differential diagnosis. Cervical spinal magnetic resonance imaging (MRI) revealed an intramedullary tumor at the C5 and C6 levels, with a tumor-associated cyst above it and spinal cord edema below it. A neurosurgical procedure was performed, and the diagnosis of ependymoma was histologically confirmed.
This case illustrates the importance of ancillary tests, which are often indispensable for determining the etiology of a medical problem but should only be used in targeted fashion and always in correlation with the clinical findings. No imaging study is needed in a classic case of carpal tunnel syndrome; an imaging study should have been performed much earlier in the present case, however, as a weak biceps reflex is incompatible with the diagnosis of carpal tunnel syndrome. Failure to pursue the implications of this finding greatly delayed the diagnosis and treatment of this patient’s tumor.
4.1 Fundamentals
Key Point
Neurologic conditions can often be correctly diagnosed from the history and physical examination alone, but ancillary tests of various kinds are nonetheless vitally important, in many patients, to confirm the diagnosis and identify the etiology precisely. In this section, we will discuss imaging studies (primarily computed tomography [CT] and MRI), electrophysiologic studies (including electroencephalography [EEG], electromyography [EMG], ENG, and evoked potentials), and ultrasonography, as well as the laboratory testing of bodily fluids (blood, cerebrospinal fluid [CSF]) and the histopathologic and cytologic study of biopsy specimens.
Whenever an ancillary diagnostic test is proposed, the specific indication for the test should be considered carefully and critically:
The test should be done only after:
Thorough and meticulous clinical history-taking and neurologic examination.
The formulation of a clinical differential diagnosis, in which all of the competing diagnoses are ranked by probability.
The test to be done is the one whose result is most likely to affect the further diagnostic and therapeutic management:
But only if this will be of clear benefit to the patient.
Only if the risks of performing it do not outweigh any potential benefit that its findings might bring.
Multiple tests that yield the same diagnostic information should not be done merely for repeated confirmation of the findings.
A test should not be done if, regardless of its result, another study will have to be performed that will probably yield at least as much information.
Only very rarely should tests be done to confirm a diagnosis that is already practically certain.
The costs must be kept in mind in view of the wide variety of tests that can be performed, some of which are very expensive.
Note
The potential consequences of any ancillary test should be discussed thoroughly with the patient and his or her family before it is performed
4.2 Imaging Studies
Key Point
Imaging studies, particularly CT and MRI, are a very important means of determining the etiology of neurologic diseases. They are applied in targeted fashion, after history-taking and physical examination, to obtain an image of the pathologic process at the site of the functional disturbance.
4.2.1 Conventional Skeletal Radiographs
Note
Conventional radiography can reveal fractures, osteolysis, degenerative changes, and postural abnormalities of the bony structures. It is now only rarely indicated, as it has largely been supplanted by tomographic imaging.
Even though newer techniques are available, plain X-rays of the skull and spine can still occasionally be of diagnostic use.
Skull X-rays are performed for very few purposes nowadays and are hardly ever indicated. (They cannot be used as a substitute for CT in head trauma; if a CT is indicated, but unavailable for some reason, then the patient should be transported to a center where a CT can be performed.) Plain films of the skull enable visualization of the following:
Fractures (though much less well than on CT; see ▶ Fig. 4.1).
Congenital malformations of the skull.
Various developmental disorders.
Skull radiographs are useless in the diagnostic evaluation of headache or intracranial processes.
Fig. 4.1 Head CT: fracture of the frontal sinus on the left side. The anterior wall of the sinus is shattered, and the sinus cells on the left are filled with blood.
Spinal X-rays are sometimes useful for the demonstration of the following:
Fractures.
Bony tumors (which, however, are more easily seen by CT or MRI—see ▶ Fig. 4.2).
Degenerative diseases and slippage (olisthesis) of the spine.
Bone infections.
Axial skeletal deformities.
Dynamic abnormalities (abnormal mobility or instability of individual spinal segments).
CT and MRI are more sensitive than plain X-rays for the demonstration of pathologic abnormalities and are generally a better aid to diagnosis.
Fig. 4.2 Chordoma of the T7 vertebral body in a 48-year-old woman. a Sagittal MR image: the spinal cord is posteriorly displaced and compressed. b Frontal MR image: after contrast medium has been administered, a tumor is seen that envelops the spinal cord.
4.2.2 Computed Tomography
Note
CT is a tomographic imaging method that employs X-rays to visualize soft tissue and bone. It is particularly suitable for the visualization of the skeleton and for emergency diagnosis. CT angiography and CT perfusion studies reveal vascular abnormalities and perfusion deficits.
Technique CT yields horizontal (axial) sectional images in which the bone and soft tissues are well seen. The images can also be digitally reconstructed in other planes, if desired. In CT, one or more rotating X-ray sources emit a beam that penetrates the tissue from many different directions, either in a single plane of section or in a spiral. The beam is attenuated to different degrees by tissues of different radiodensities, and its amplitude after attenuation is measured by a circular array of up to 320 detectors and amplifiers. From the resulting pattern of attenuation, the radiodensity at each location (voxel) in the interior of the brain is calculated by specialized computer software. There may be, for example, 512 × 512 voxels in each axial section. A visual image is then created in which the radiodensity at each voxel is depicted on an analogue grayscale; anatomic structures can be visualized because of the differences in radiodensity between adjacent tissues ( ▶ Fig. 4.3). Bony structures are well seen in CT images, especially in three-dimensional CT reconstructions ( ▶ Fig. 4.4). Blood vessels, too, can be visualized.
Currently, spiral CT scanners are in widespread use: these contain multiple X-ray sources and detectors that rotate in a spiral, that is, the X-ray tube(s) swivels around the patient’s head while the table on which the patient is lying is slowly advanced, at constant velocity, along the long axis of the body. The resulting spiral dataset is numerically converted into axial sections. This technique shortens the time required for a complete scan.
The radiation load associated with a CT scan of the head is roughly that of a chest X-ray. CT is somewhat less expensive than MRI.
Indications The indications for, and diagnostic utility of, CT versus MRI are shown in ▶ Table 4.1.
Location and type of pathology | CT | MRI |
Brain atrophy | +++ | +++ |
Acute infarct | ++ | +++ |
Older infarct | ++ | +++ |
Lacunar state | +++ | +++ |
Acute intraparenchymal hemorrhage | ++ | +++ |
Subarachnoid hemorrhage | +++ | + |
Aneurysm | + | ++ |
Venous thrombosis | + | +++ |
Brain tumor (cerebral hemispheres) | ++ | +++ |
Pituitary tumor | + | +++ |
Brain metastases | +++ | +++ |
Carcinomatous meningitis | – | ++ |
Hydrocephalus | +++ | +++ |
Head trauma: skull injury | +++ | + |
Head trauma: brain injury | ++ | +++ |
Head trauma: acute sub- or epidural hematoma | +++ | +++ |
Meningoencephalitis | ++ | +++ |
Abscess | ++ | +++ |
Parasitic cyst(s) | + | +++ |
Arachnoid cyst | ++ | +++ |
Posterior fossa | + | +++ |
Pathology of the white matter | + | +++ |
Multiple sclerosis | – | +++ |
Atlanto-occipital joint | + | +++ |
Lesions of the skull | +++ | + |
Lesions of the spine (bone) | ++ | ++ |
Lesions of the spinal cord and nerve roots | + | +++ |
Note: +++ = most suitable study, usually adequate for diagnosis; ++ = study generally useful; + = study occasionally necessary or indicated in addition to other tests; – study not useful. | ||
Fig. 4.3 Normal CT scan of the head. a Note the symmetrical, normal-sized frontal and occipital horns of the lateral ventricles. The cerebral cortex and deep white matter are clearly demarcated from each other, and the falx cerebri is seen in both the frontal and occipital regions. Several blood vessels can be seen. Also, note the bilateral calcifications of the choroid plexus of the lateral ventricles. b Some of the blood vessels around the base of the brain (arrows) are well seen after the administration of contrast medium.
Fig. 4.4 Three-dimensional CT reconstruction of the cervical spine.
Special CT Techniques
The administration of intravenous contrast medium increases the sensitivity and specificity of CT scanning.
Blood–tissue (or blood–CSF) barrier: the penetration of contrast medium into brain tissue or tumor tissue (contrast enhancement) indicates disruption of the blood–tissue barrier or the blood–CSF barrier.
Blood vessels can also be selectively imaged with the injection of contrast medium (CT angiography). This technique reveals vascular lesions such as aneurysms, intra-arterial plaques, stenosis, and occlusion.
Perfusion CT ( ▶ Fig. 4.5) employs short image-acquisition times with the simultaneous injection of contrast medium to enable the visualization of brain perfusion.
4.2.3 Magnetic Resonance Imaging
Note
MRI employs magnetic fields and radio waves to induce hydrogen atoms in the body’s tissues to emit signals that can be displayed on sectional images. MRI is particularly suitable for the visualization of soft-tissue lesions but can also be used for vascular imaging and for functional diagnostic studies.
MRI is a sectional imaging technique that does not rely on the use of ionizing radiation.
Technical description The underlying physical principles of MRI are as follows: the most common atomic nuclei in all tissues of the body are hydrogen nuclei (protons). They are positively charged and possess an intrinsic magnetic property known as “spin,” which can be imagined as a rotation of the proton around its own axis. Each proton thus has its own small magnetic field. A proton to which an external magnetic field is applied orients itself in the field like a compass needle ( ▶ Fig. 4.6). When the protons in a particularly bodily tissue are aligned in this way, and then stimulated with a radiofrequency pulse at a particular frequency (the resonance or Larmor frequency), they will take on energy and reorient themselves opposite the field. Once the stimulating pulse is switched off, the protons release the energy that they previously absorbed as they return to their original orientation. The released energy can be detected with a radio antenna or coil and is called the magnetic resonance signal. The signals from different points in a slab of tissue are distinguished from one another with gradient fields, that is, smaller magnetic fields overlying the main field. The MR image is a grayscale map of the different intensities of MR signal coming from the tissue ( ▶ Fig. 4.7) and can be computed in any desired plane of section. Gadolinium–DTPA can be given intravenously as a contrast medium for MRI. Caution is advised in patients with renal dysfunction, in whom gadolinium may lead to nephrogenic systemic fibrosis.
The MR signal intensity of tissue is a function of its local physical and chemical properties, which determine, for example, the length of time that the hydrogen nuclei need to return to their initial orientation (T1 and T2 relaxation times). The signal intensity is further influenced by the technical parameters of the scanner (e.g., the strength of the applied magnetic field and the frequency of the stimulating impulses).
Indications The MRI signal characteristics of various normal and pathologic tissues in the brain are listed in ▶ Table 4.1. The main types of signal abnormality that are important for neurologic diagnosis are indicated in ▶ Table 4.2.
Tissue | T1-weighted image | T2-weighted image |
Cerebrospinal fluid | Dark | Very bright |
Brain | ||
White matter | Bright | Slightly dark |
Gray matter | Slightly dark | Slightly bright |
MS plaque | Intermediate to dark | Bright |
Bland infarct | Dark | Bright |
Tumor/metastasis | Dark | Bright |
Meningioma | Intermediate | Intermediate |
Abscess | Dark | Bright |
Edema | Dark | Bright |
Calcification | Intermediate or bright | Intermediate or dark |
Fat | Very bright | Intermediate to dark |
Cyst | ||
Containing mostly water | Dark | Very bright |
Containing proteinaceous fluid | Intermediate to bright | Very bright |
Containing lipids | Very bright | Intermediate to dark |
Bone | ||
Cortical bone | Very dark | Very dark |
Yellow bone marrow | Very bright | Intermediate to dark |
Red bone marrow | Intermediate | Slightly dark |
Bone metastasis | ||
Lytic | Dark | Intermediate to bright |
Sclerotic | Dark | Dark |
Cartilage | ||
Fibrous | Very dark | Very dark |
Hyaline | Intermediate | Intermediate |
Intervertebral disk | ||
Normal | Intermediate | Bright |
Degenerated | Intermediate to dark | Dark |
Muscle | Dark | Dark |
Tendons and ligaments | ||
Normal | Very dark | Very dark |
Inflamed | Intermediate | Intermediate |
Torn | Intermediate | Bright |
Contrast enhancement with gadolinium–DTPA | ||
Low concentration | Very bright | Bright |
High concentration | Intermediate to dark | Very dark |
Hematoma | ||
Hyperacute | Intermediate | Intermediate to bright |
Acute | Intermediate to dark | Dark to very dark |
Subacute | Bright rim, intermediate | Bright rim, dark center, later all bright |
Chronic | Dark rim, bright center, later all dark | Dark rim, bright center, later all dark |
Abbreviations: DTPA, diethylenetriaminepentaacetic acid; MS, multiple sclerosis. Source: Adapted from Edelman RR, Warach S. Magnetic resonance imaging (1). N Engl J Med 1993;328(10):708–716. Note: Bright = hyperintense; dark = hypointense; intermediate = isointense in comparison to brain tissue. | ||
Fig. 4.5 Perfusion CT in acute occlusion of the left middle cerebral artery (MCA; upper row of images, a–c) and after reperfusion (lower row, d–f). a CT without contrast medium reveals no abnormality. b Visualization of regional cerebral blood flow (rCBF), as calculated from the regional blood volume and the mean contrast-medium transit time (MTT), reveals hypoperfusion of the entire left MCA territory. c MTT is prolonged in the MCA distribution. d After successful reperfusion by thrombolysis, there is no infarct; e the blood flow and f transit time are normal again.
Fig. 4.6 Physical principles of magnetic resonance imaging. Adapted from Edelman RR, Warach S. Magnetic resonance imaging (1). N Engl J Med 1993;328(10):708–716. a The magnetic axes of the protons are randomly distributed over space. b When a magnetic field B0 is applied to the protons, they align themselves either parallel or antiparallel to the field. A proton aligned parallel to B0 has a lower energy than one aligned antiparallel to it; therefore, most protons have a parallel alignment at first. If radio waves of a specific frequency (the Larmor frequency) are now applied, protons can absorb the energy they need to “flip” from the lower-energy to the higher-energy state, thereby becoming antiparallel to the field B0. The flipped protons then gradually return to the parallel, lower-energy state (relaxation). The speed of relaxation is determined by two tissue-specific constants called T1 and T2. c After the 90-degree excitatory pulse is delivered, the protons precess in the transverse plane. They are in phase at first, and therefore give off a maximally intense signal. Very small inhomogeneities of the magnetic field make the protons precess at slightly different speeds, resulting in “dephasing” and loss of signal intensity. This process, which takes only a few milliseconds, is called T2 relaxation. The MR signal is usually measured during T2 relaxation. The restoration of magnetization parallel to B0 is a somewhat slower process, called T1 relaxation. Several techniques (e.g., gradient echo, spin echo) are used to generate the largest possible MR signal.
Fig. 4.7 a–h Normal MRI of the brain in 5-mm sections from base to vertex.
MR Angiography
When the spin-echo technique is used in MRI scanning, flowing blood gives rise to a signal only if it is excited by two radio wave pulses that arrive one after the other at the same location. If the blood passes rapidly through the imaging plane, the bit of blood that received the first excitatory pulse has already flowed away by the time the second pulse arrives, and no signal is generated—the vessel appears dark (there is a “flow void”). However, if the blood flows slowly enough to receive both pulses in the imaging plane, the vessel appears bright. When gradient-echo sequences are used, flowing blood always appears bright, while stationary tissue appears dark.
Computer algorithms can combine the individual sectional images, processing them to generate a projectional image resembling a conventional angiogram; this is called a magnetic resonance angiogram ( ▶ Fig. 4.8). The technique that exploits signal timing and flow voids is called time-of-flight magnetic resonance angiography, or TOF-MRA. It can be used for the noninvasive diagnosis of, for example, a carotid artery occlusion.
Fig. 4.8 MR angiography of the intracranial vessels. a Coronal and b axial projections of the circle of Willis, revealing the internal carotid artery (1), the middle cerebral artery(2), the anterior cerebral artery (3), the vertebral artery (4), the basilar artery (5), and the posterior cerebral artery (6).
Contrast-enhanced MR angiography is now being performed increasingly often. In this technique, the signal is produced not by the flowing of the blood per se, but by the contrast medium in the bloodstream ( ▶ Fig. 4.9).
Fig. 4.9 Contrast-enhanced MR angiography of the cervical vessels. Coronal image. The visualized structures include the aortic arch (1) and the cervical and brachial arteries that emerge from it: the brachiocephalic trunk (2), the subclavian artery (3), the axillary artery (4), the common carotid artery (5), the internal carotid artery (6), the external carotid artery (7), the vertebral artery (8), and the basilar artery (9). The only abnormality here is an unusual elongation of the basilar artery.
Susceptibility-weighted MR sequences have also entered into widespread clinical use. They permit the demonstration of acute embolic or thrombotic vascular occlusion ( ▶ Fig. 4.10).
Fig. 4.10 Susceptibility-weighted imaging (SWI). a MR angiogram of the arteries of the base of the brain in a patient with embolic occlusion of the left posterior cerebral artery (arrow). b SWI reveals the embolus as a signal void (arrow).
Further MR Techniques
The passage of contrast medium through the organs can be detected with rapid imaging sequences, so that organ perfusion can be measured (perfusion MRI). The technique of perfusion MRI is based on the loss of signal caused by contrast media such as gadolinium on gradient-echo images.
The diffusive movement of hydrogen nuclei (protons) can also be visualized with special diffusion-weighted sequences (diffusion MRI). This technique enables the detection of acute ischemia, because protons in ischemic tissue diffuse much less readily in the initial hours and days after the event. The use of diffusion gradients in all three spatial dimensions (diffusion tensor imaging) enables detection of the preferential direction of diffusion in each voxel of tissue. This technique is used to depict fiber tracts and display their course between different regions of the brain ( ▶ Fig. 4.11).
Fig. 4.11 Demonstration of nerve fiber trajectories by MRI with diffusion tensor imaging (DTI). a T2-weighted MRI reveals an arteriovenous malformation (AVM) in the posterior portion of the left temporal lobe. b DTI reveals that the visual pathway (green) lies superior to the AVM as it courses toward the occipital lobe. (This view is from above, and the AVM is therefore on the left side of the image.)
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