Neurology_Adams

Neurology_Adams. Many of the enzymes found in serum are known to rise in CSF under conditions of disease, usually in relation to a rise in the CSF protein. None of the enzyme changes has proved to be a specific indicator of neurologic disease with the possible exception of lactic dehydrogenase, especially isoenzymes 4 and 5, which are derived from granulocytes and are elevated in bacterial meningitis but not in aseptic or viral meningitis. Lactic dehydrogenase is also elevated in cases of meningeal tumor infiltration, particularly lymphoma, as is carcinoembryonic antigen; the latter, however, is not elevated in bacterial, viral, or fungal meningitis. As to lipids, the quantities in CSF are small and their measurement is difficult.


Neurology_Adams

Neurology_Adams. The catabolites of the catecholamines can be measured in the CSF. Homovanillic acid (HVA), the major catabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA), the major catabolite of serotonin, are normally present in the spinal fluid; both are five or six times higher in the ventricular than the lumbar CSF. The levels of both catabolites are reduced in patients with idiopathic and drug-induced parkinsonism.


Neurology_Adams

Neurology_Adams. A century ago, Harvey Cushing introduced the use of plain x-ray films of the cranium as part of the study of the neurologic patient. Plain skull films demonstrate fractures, changes in contour of the skull, bony erosions and hyperostoses, infection in paranasal sinuses and mastoids, and changes in the basal foramina. Calcified structures such as the pineal gland were time-honored landmarks of midline structures, allowing measurements of the displacement of intracranial contents. Plain films of the spine are able to demonstrate destructive lesions resulting from degenerative processes as well neoplastic, dysplastic, and infectious diseases. It also detects fracture dislocations, spondylolistheses, and spinal instability, utilizing images acquired during flexion and extension maneuvers. However, refinements of imaging techniques have greatly increased the yield of valuable information. Without question the most important advances in neuroradiology have come about with the development of


Neurology_Adams

Neurology_Adams. refinements of imaging techniques have greatly increased the yield of valuable information. Without question the most important advances in neuroradiology have come about with the development of CT and MRI.


Neurology_Adams

Neurology_Adams. In this procedure, x-radiation is attenuated as it passes successively through the scalp, skull, CSF, cerebral gray and white matter, and blood vessels. The intensity of the exiting radiation relative to the incident radiation is measured, the data are integrated, and two-dimensional images are reconstructed by computer. This major achievement in methodology, attributed to Hounsfield and others, permitted the technologic advance from plain radiographs of the skull to reconstructed images of the cranium and its contents in any plane. The differing densities of bone, CSF, blood, and gray and white matter are distinguishable in the resulting picture with great clarity. One can see and measure the sizes of hemorrhage, infarction, contusion, edematous brain, abscess, tumor, and also determine the shape and position of the ventricles and midline structures. The radiation exposure is only modestly greater than that from plain skull films. The machinery can be manipulated to reduce radiation


Neurology_Adams

Neurology_Adams. the shape and position of the ventricles and midline structures. The radiation exposure is only modestly greater than that from plain skull films. The machinery can be manipulated to reduce radiation exposure where this limitation is desirable, for example, in children.


Neurology_Adams

Neurology_Adams. As illustrated in Fig. 2-1, in transverse (axial) section of the brain, one sees the cortex and underlying subcortical white matter, the caudate and lenticular nuclei and the internal capsules and thalami. The position and width of all the major sulci and fissures can be measured, and the optic nerves and medial and lateral rectus muscles stand out clearly in the posterior parts of the orbit. The brainstem, cerebellum, and spinal cord are easily visible in the scan at appropriate levels. The scans are also useful in imaging parts of the body that surround peripheral nerves and plexuses, thereby demonstrating tumors, inflammatory lesions, and hematomas that involve these nerves. Intravenous administration of radiopaque material (contrast) can be used with CT to visualize regions where the blood–brain barrier has been disrupted from tumors, demyelination, and infection.


Neurology_Adams

Neurology_Adams. In imaging of the head, CT has a number of advantages over MRI, the most important being safety when metal may be present in the body, shorter examination time, and the clarity of blood from the moment of bleeding. Other appealing aspects are its broader availability, lower cost, larger aperture of the machine that reduces patient claustrophobia, and equivalent or superior visualization of calcium, fat, and bone, particularly of the skull base and vertebrae (see Fig. 2-1D). If constant monitoring and use of life support equipment is required during the imaging procedure, it is accomplished more readily by CT than by MRI. Advances in CT technology have greatly increased the speed of the scanning procedure and have also made possible the visualization, with great clarity, of the cerebral vasculature (CT angiography; see further on).


Neurology_Adams

Neurology_Adams. CT also demonstrates the bony structures of the vertebral column in greater detail than is available with conventional x-ray. Herniated lumbar and cervical discs, cervical spondylotic bars and bony spurs encroaching on the spinal cord or roots, and spinal cord tumors can be visualized with clarity. MRI provides even sharper visualization of the spinal canal and its contents as well as the vertebrae and intervertebral discs as discussed further on.


Neurology_Adams

Neurology_Adams. Myelography utilizes intrathecal contrast material to demonstrate the contours of the spinal cord and spinal roots. It can be accomplished either by conventional fluoroscopy or by CT. By injecting water-soluble radiopaque contrast through an LP needle and then placing the patient in the Trendelenberg position, the entire spinal subarachnoid space can be visualized (Fig. 2-2A–C). The procedure is almost as harmless as the LP except for cases of complete spinal block, in which high concentrations of contrast near the block can cause pain and regional myoclonus. Iophendylate (Pantopaque), a formerly used fat-soluble dye, is still approved by the FDA but is now employed only in special circumstances (visualizing the upper level of a spinal canal lesion that completely obstructs the flow of water soluble dye). If iophendylate is left in the subarachnoid space, particularly in the presence of blood or inflammatory exudate, it may incite arachnoiditis of the spinal cord and brain. MRI,


Neurology_Adams

Neurology_Adams. of water soluble dye). If iophendylate is left in the subarachnoid space, particularly in the presence of blood or inflammatory exudate, it may incite arachnoiditis of the spinal cord and brain. MRI, because of its ability to clearly demonstrate intrathecal structures has largely supplanted contrast myelography as discussed in a later section.


Neurology_Adams

Neurology_Adams. Risks of CT The primary risk of CT is radiation exposure, and overexposure can have clinical consequences ranging from relatively benign alopecia to leukomalacia and neoplasia. The interested reader should refer to FDA guidelines on the subject (http://www.fda.gov/Radiation-emittingProducts/RadiationEmittingProductsandProcedures/MedicalImaging/MedicalX-Rays/ucm115317.htm). Given the need for repeated CT examinations in certain patients, tracking of total radiation exposure may be advisable and may find greater use in the future. CT is usually deferred during pregnancy unless the mother’s health is at imminent risk (i.e., following trauma). The potential harm to a fetus from radiation depends on gestational age and total absorbed dose. It is noteworthy that the fetal radiation dose from maternal cranial CT is lower than from maternal pelvic CT.


Neurology_Adams

Neurology_Adams. The risks of contrast infusion include allergic reactions and nephropathy, which is most often transient and reversible, but can be more severe in patients with underlying renal dysfunction. Intravenous contrast in generally withheld if the glomerular filtration rate (calculated GFR) is less than 30 mL/min/1.73 m2; if GFR is 30 to 60, hydration and, discontinuation of potentially nephrotoxic medications should precede the administration of contrast, particularly nonsteroidal anti-inflammatory agents, cisplatin-containing chemotherapy and aminoglycoside antibiotics. Repeated infusions of contrast should be done cautiously.


Neurology_Adams

Neurology_Adams. Many engineers, mathematicians, and physicists made contributions to the technology of nuclear MRI, and a Nobel Prize was awarded to Lauterbur and Mansfield for its development. MRI provides images in any plane, and it has the advantage over CT in using nonionizing energy and providing higher resolution views, and improved contrast between different structures within the nervous system. For visualization of many neurologic lesions, MRI is the preferred procedure.


Neurology_Adams

Neurology_Adams. Nuclear magnetic resonance can be detected from several isotopes, but current technology uses mainly signals derived from hydrogen atoms because hydrogen is the most abundant element in tissue and yields the strongest magnetic signal as discussed by Horowitz. The image is essentially a map of the hydrogen content of tissue, therefore reflecting largely the water concentration, but influenced also by the physical and chemical environment of the hydrogen atoms. MRI is accomplished by placing the patient within a powerful magnetic field, causing certain endogenous isotopes to be aligned in the longitudinal orientation of the magnetic field. Application of a brief (few milliseconds) radiofrequency (RF) pulse into the field changes the axis of alignment of the atoms. When the RF pulse ceases, the atoms return to their original alignment and the RF energy that was absorbed is then emitted by the isotopes, producing an electric signal that is detected by receiver coils. To create contrasting


Neurology_Adams

Neurology_Adams. atoms return to their original alignment and the RF energy that was absorbed is then emitted by the isotopes, producing an electric signal that is detected by receiver coils. To create contrasting tissue images from these signals, the RF pulse must be repeated many times (a pulse sequence), the signals being measured after the application of each pulse. The scanner stores the signals as a matrix of data, which is subjected to computer analysis that allows reconstruction of two-dimensional images.


Neurology_Adams

Neurology_Adams. The terms T1and T2-weighting refer to the time constants for proton relaxation; these may be altered to highlight certain features of tissue structure. In T1-weighted images, CSF appears dark and gray matter is hypointense to white matter. In T2-weighted images, CSF appears bright, and gray matter is hyperintense to white matter. Lesions within the white matter, such as the demyelination of multiple sclerosis, are more easily seen on T2-weighted images, appearing hyperintense against normal white matter (Table 2-3).


Neurology_Adams

Neurology_Adams. A high degree of contrast is seen between white and gray matter on both T1and T2-weighted images, allowing the identification of many discrete structures (Fig. 2-3). Lesions near the skull base and within the posterior fossa, in particular, are seen with greater clarity on MRI compared to CT, unmarred by signals from adjacent skeletal structures. The products of disintegrated RBCs—oxyhemoglobin, deoxyhemoglobin, methemoglobin, and hemosiderin—can be recognized, enabling one to approximate the age of hemorrhages and to follow their resolution, as discussed in Chaps. 33 and 34. Gradient-echo (GRE), or susceptibility weighted imaging (SWI), is especially sensitive to blood and its breakdown products that appear hypointense.


Neurology_Adams

Neurology_Adams. As mentioned earlier, MRI of the spine provides clear images of the vertebral bodies, intervertebral discs, spinal cord, and cauda equina (Fig. 2-2D–F). Abnormalities such as syringomyelia, herniated discs, tumors, epidural or subdural hemorrhages, areas of demyelination, and abscesses are well delineated (see Modic). Additional radiofrequency pulses can be applied to T1and T2-weighted images in order to selectively suppress signal from fluid or fat. The FLAIR (fluid-attenuated inversion recovery) sequence is a T2-weighted sequence in which the bright signal of fluid that is not contained within tissues is suppressed. This is a particularly useful sequence for visualizing lesions located near CSF compartments. Fat suppression, which can be applied to T1 or T2 sequences, can be used to improve the demonstration of inflammation of the optic nerve, visualize pathologic inflammation within the vertebral bodies, and show thrombus within the false lumen of a cervical dissection.


Neurology_Adams

Neurology_Adams. Diffusion-weighted imaging (DWI) is a technique that measures the free diffusion of water molecules within tissue. Preferential movement of water molecules along a particular direction, for example, parallel to white matter tracts, is referred to as anisotropy (i.e., nonisotropic movement). Many abnormal processes can produce anisotropy as well. In acute ischemic stroke, failure of the sodium-potassium ATPase pump leads to cellular swelling and reduced intercellular space, thus limiting the free movement of water and producing hyperintensity on DWI. This imaging technique reveals the abnormalities of ischemic stroke earlier than standard T1or T2-weighted MRI, or CT. Pus-filled abscesses and hypercellular tumors can also show DWI hyperintensity, reflecting the limitation of free diffusion of water in these lesions.


Neurology_Adams

Neurology_Adams. True restricted diffusion, appearing hyperintense on the DWI sequence in acute infarction, is hypointense on a related sequence termed apparent diffusion coefficient (ADC). If the hyperintense DWI signal is also hyperintense on ADC, then diffusion is termed facilitated rather than restricted. This phenomenon is seen when the free movement of water within a tissue becomes increasingly isotropic, as with vasogenic edema. Therefore, the interpretation of DWI signal hyperintensity must be gauged in the context of the ADC signal in the same region. The administration of gadolinium, a paramagnetic agent that accelerates the process of proton relaxation during the T1 sequence of MRI, permits even sharper definition and highlights regions surrounding many types of lesions where the blood–brain barrier has been disrupted in the brain, spinal cord, or nerve roots. Limitations and Safety of MRI


Neurology_Adams

Neurology_Adams. Limitations and Safety of MRI The degree of cooperation in holding still that is required to perform MRI limits its use in young children and in the cognitively impaired. Some form of sedation may be required in these individuals and most hospitals have services to safely accomplish conscious sedation for this purpose. Studying a patient who requires a ventilator is also difficult but manageable by using either manual ventilation or nonferromagnetic ventilators.


Neurology_Adams

Neurology_Adams. The main dangers in the use of MRI are torque, dislodgement or heating of metal clips on blood vessels, of dental devices and other ferromagnetic objects, and of small metal fragments in the orbit, the last of these often acquired unnoticed by operators of machine tools. For this reason it is wise, in appropriate patients, to obtain plain radiographs of the orbits so as to detect metal in these regions. Corneal metal fragments can be removed by an ophthalmic surgeon if an MRI is necessary. The presence of a cardiac pacemaker, defibrillator, or implanted stimulator in the brain or spinal cord is an absolute contraindication to the use of MRI as the magnetic field induces unwanted currents in the device and the wires exiting from it. However, many new implantable medical devices have been developed that are unaffected by and do not distort the magnetic field. Most of the newer, weakly ferromagnetic prosthetic heart valves, joint prostheses, some cochleae implants, intravascular access


Neurology_Adams

Neurology_Adams. developed that are unaffected by and do not distort the magnetic field. Most of the newer, weakly ferromagnetic prosthetic heart valves, joint prostheses, some cochleae implants, intravascular access ports, aneurysm clips, and ventricular shunts and adjustable valves do not represent an untoward risk for magnetic imaging although shunt valves may require resetting after MRI. An extensive list of devices that have been tested for their ferromagnetic susceptibility and their safety in the MRI machine can be found at www.mrisafety.com. MRI entails some risk in these situations unless there is direct knowledge of the type of material contained in the device. It should be noted that devices or materials that are deemed safe for 1.0 or 1.5 Tesla scanners may not be compatible with higher magnetic field strength scanners.


Neurology_Adams

Neurology_Adams. Because of the development of cataracts in the fetuses of animals exposed to MRI, there has been hesitation in performing MRI in pregnant patients, especially in the first trimester. However, current data indicate that imaging may be performed provided that the study is medically indicated. In a study of 1,000 pregnant MRI technicians who entered the magnetic field frequently (the magnet remains on between procedures), no adverse effects on the fetus could be discerned (Kanal et al).


Neurology_Adams

Neurology_Adams. An additional risk of the administration of gadolinium is nephrogenic systemic fibrosis, a severe cutaneous sclerosing disease. Most instances occur in patients with preexisting renal failure, for which reason it has become common to obtain BUN and creatinine measurements before administering gadolinium. The problem had not been appreciated initially in part because of its rarity (the frequency has not been well established) and because of a delay in the appearance of sclerosis in the kidney and skin, of several days to months.


Neurology_Adams

Neurology_Adams. Many types of MRI image artifacts are known, most having to do with technical aspects of the electronic characteristics of the magnetic field or of the mechanics involved in the imaging procedure (for details, see Morelli et al). Among the most common and problematic are CSF flow artifacts in the thoracic spinal cord, giving the impression of an intradural mass; distortions of the appearance of structures at the base of the brain from ferromagnetic dental appliances; and lines across the entire image induced by vascular pulsations and patient movement.


Neurology_Adams

Neurology_Adams. The increasing use of MRI and the sensitivity of current machines have had the unintended effect of revealing a large number of unimportant findings that create undue worry and often trigger neurologic consultation. Moreover, many lesions are not referable to the clinical problem at hand. A surprising number of incidental brain lesions are exposed by indiscriminate use of imaging. For example, a large survey of asymptomatic adults who were being followed in the “Rotterdam Study” is in accord with several prior studies in which cerebral aneurysms were found in approximately 2 percent, meningiomas in 1 percent, and a smaller but not insignificant number of vestibular schwannomas and pituitary tumors; the meningiomas, but not the aneurysms, increased in frequency with age. One percent had the Chiari type I malformation, and a similar number had arachnoid cysts. In addition, 7 percent of adults older than age 45 years had occult strokes, mostly lacunar. Because this survey was performed


Neurology_Adams

Neurology_Adams. Chiari type I malformation, and a similar number had arachnoid cysts. In addition, 7 percent of adults older than age 45 years had occult strokes, mostly lacunar. Because this survey was performed without gadolinium infusion, it might be expected that even more small asymptomatic lesions could be revealed (Vernooij et al).


Neurology_Adams

Neurology_Adams. These are noninvasive techniques for visualizing the intracranial and cervical arteries. They can reliably detect intracranial vascular lesions and extracranial arterial stenosis and are supplanting conventional angiography. They approach the radiographic resolution of catheter-based angiography, but do not engender the risk of selective arterial catheterization (Fig. 2-4). Visualization of the cerebral veins is also possible by CT (Fig. 2-4D) and MRI.


Neurology_Adams

Neurology_Adams. CT angiography requires contrast administration. In comparison, MR angiography can be performed without contrast, using the “time-of-flight” technique. This data can be reconstructed into an image that reflects flow-related enhancement. The signal obtained from time-of-flight MRA represents flow through the lumen of a vessel, rather than the configuration as obtained by contrast opacification. The use of these and other methods for the investigation of carotid artery disease is discussed further below and in Chap. 35, on cerebral vascular disease.


Neurology_Adams

Neurology_Adams. This technique is a valuable method for the diagnosis and treatment of aneurysms, vascular malformations, narrowed or occluded arteries and veins, arterial dissections, and angiitis. To a large extent, CT and MRI angiographic techniques have supplanted the diagnostic role of catheter angiography, but the latter remains necessary for a variety of conditions, particularly small vascular malformations. It is also possible to introduce thrombolytic substances and mechanical devices through catheters for the treatment of cerebrovascular disease.


Neurology_Adams

Neurology_Adams. A needle is placed in the femoral or brachial artery; a cannula is then threaded through the needle and along the aorta and the arterial branches to be visualized. In this way, a contrast agent is injected to visualize the arch of the aorta, the origins of the carotid and vertebral systems, and the extensions of these systems through the neck and into the cranial cavity and the vasculature in and surrounding the spinal cord. This allows the visualization of the cerebral and spinal cord vessels to less than 1 mm in lumen diameter. With refinements in technique it is possible to produce images of the major cervical and intracranial arteries with relatively limited amounts of contrast medium introduced through small catheters.


Neurology_Adams

Neurology_Adams. Angiography is not altogether without risk. Overall morbidity from the procedure is approximately 2.5 percent, mainly in the form of worsening of a preexistent vascular lesion or from complications at the site of artery puncture. Occasionally, cerebral or systemic ischemic lesions are produced, the result of either particulate atheromatous material dislodged by the catheter, thrombus formation at or near the catheter tip, vasospasm, or more often by dissection of the artery by the catheter. A cervical myelopathy is a rare but disastrous complication of vertebral artery contrast injection; the problem is heralded by pain in the back of the neck immediately after injection. Progressive cord ischemia from an ill-defined vascular process ensues over the following hours. For these reasons, the procedure should not be undertaken unless it is deemed necessary to obtain a clear diagnosis or in anticipation of surgery that requires a definition of the location of the vessels.


Neurology_Adams

Neurology_Adams. This imaging modality is a contrast-based technique that can be performed with both CT and MRI. Images are rapidly and serially acquired as the contrast transits through the vasculature and parenchyma. A time-intensity curve is produced, from which measurements of cerebral blood flow, cerebral blood volume, and transit time can be derived. Perfusion imaging has provided a means of detecting regions of ischemic tissue, and to monitor the elevated blood volume in certain brain tumors.


Neurology_Adams

Neurology_Adams. The tissue concentrations of a variety of cellular metabolites can be determined with the technique of magnetic resonance spectroscopy (MRS). Among these substances, N-acetyl aspartate (NAA) is a marker of neuronal integrity and is decreased in both destructive lesions and in circumstances in which there is a reduction in the density of neurons (e.g., edema or glioma that increases the distance between neurons). Choline (Cho), a marker of membrane turnover, is elevated in some rapidly dividing tumors. Therefore, compared to normal white matter, the spectrogram of a glioma characteristically shows decreased NAA and increased Cho. It is possible to measure a number of other metabolites such as myoinositol, creatine, and lactate that find occasional clinical utility.


Neurology_Adams

Neurology_Adams. A technique based on DWI, termed diffusion tensor imaging (DTI), integrates measurements of the amount of anisotropy with its directionality to model axonal tracts in the brain. This modality detects damage to, or displacement of white matter tracts because of trauma, vascular injury, or tumor. Tractography is also occasionally used in surgical planning to localize critical white matter tracts in order to avoid their transection during operations.


Neurology_Adams

Neurology_Adams. In the last decades, several techniques of functional imaging have been introduced to study the activation of regions of cerebral cortex during mental and physical actions or experiences. The MRI-based functional imaging technique (functional MRI, or fMRI) shows changes in local cerebral blood oxygenation, a surrogate for local neuronal metabolic activity. These changes are quantified as the blood oxygen level-dependent (BOLD) signal, and evolve over the 10 to 15 s following a change in neuronal activity (Fig. 2-5). In addition to its research application in cognitive neuroscience, this technique also has clinical utility, including presurgical planning in tumor and epilepsy surgery.


Neurology_Adams

Neurology_Adams. Positron emission tomography (PET) produces images that reflect the regional concentration of systemically administered radioactive compounds. Positron-emitting isotopes (mainly 11C, 18F, and 15O) are produced in a cyclotron or linear accelerator, injected into the patient, and incorporated into biologically active compounds in the body. The concentration of these tracers in various parts of the brain is determined by an array of radiation detectors and tomographic images are constructed by techniques similar to those used in CT and MRI.


Neurology_Adams

Neurology_Adams. MRI. Local patterns of cerebral blood flow, oxygen uptake, and glucose utilization can also be measured by PET, and the procedure has proved to be of value in both detecting and grading brain tumors, distinguishing tumor tissue from radiation necrosis, localizing epileptic foci, and, in differentiating types of degenerative diseases. The technique has been applied to specially labeled ligands of beta-amyloid, producing images of the deposition of this protein in Alzheimer disease. This approach may become increasingly important in the study of degenerative diseases and their response to treatment. The ability of the technique to quantitate neurotransmitters and their receptors also promises to be of importance in the study of Parkinson disease and other degenerative conditions. However, this technology is costly and does not always add to the certainty of diagnosis. A representative PET of the brain is shown in Fig. 2-6.


Neurology_Adams

Neurology_Adams. Single-photon emission computed tomography (SPECT), a similar technique, uses isotopes that do not require a cyclotron for their production. Radioligands (usually containing iodine) are incorporated into biologically active compounds, which, as they decay, emit a single photon. This procedure allows the study of regional cerebral blood flow under conditions of cerebral ischemia and in degenerative diseases of the cortex, or during increased tissue metabolism (e.g., seizures and actively growing tumors). Once injected, the isotope localizes rapidly in the brain, with regional absorption proportional to blood flow, and is then stable for an hour or more. It is thus possible, for example, to inject the isotope at the time of a seizure, while the patient is undergoing video and electroencephalographic monitoring, and to scan the patient soon after. The limited anatomic resolution provided by SPECT limits its clinical usefulness, but it is more easily available than other functional


Neurology_Adams

Neurology_Adams. monitoring, and to scan the patient soon after. The limited anatomic resolution provided by SPECT limits its clinical usefulness, but it is more easily available than other functional imaging techniques. PET and SPECT techniques that use I123 labeled dopamine, have been introduced and offer the possibility of imaging striatal dopamine and assisting in the diagnosis of parkinsonian disorders (see Chap. 38).


Neurology_Adams

Neurology_Adams. An ultrasound technique may be used to insonate the cervical carotid and vertebral arteries, and the temporal arteries for the study of cerebrovascular disease. Their greatest use is in detecting and estimating the degree of stenosis of the origin of the internal carotid artery. In addition to providing an acoustic image of the vascular structures, the Doppler frequency shift caused by flowing red blood cells creates a display of velocities at each site in a vessel. The two techniques combined have been called “carotid duplex”; they allow an accurate localization of the locus of maximal stenosis as reflected by the highest rates of flow and turbulence. The display scale for the Doppler shift is color coded so as to make the insonated image and flow map easier to view and interpret.


Neurology_Adams

Neurology_Adams. This ultrasound technique using different sound frequencies and intensities, has also become a principal methodology for clinical study of the fetal and neonatal brain. Different tissues have specific acoustic impedances and send echoes back to the transducer, which displays them as waves of variable height or as points of light of varying intensity. In this way, one can obtain images in the neonate of choroid plexus, ventricles, and central nuclear masses. Usually several coronal and parasagittal views are obtained by placing the transducer over open fontanelles or the child’s thin calvarium. Intracerebral and subdural hemorrhages, mass lesions, and congenital defects can readily be visualized.


Neurology_Adams

Neurology_Adams. Similar instruments are used to insonate the basal vessels of the circle of Willis in adults (“transcranial Doppler”). The transcranial Doppler uses a 2-MHz pulsed signal that is able to pass through the calvarial bone and then receives a frequency-shifted signal from the blood flowing in the lumen of the basal vessels. This allows the detection of vascular stenoses and the greatly increased blood flow velocity caused by vasospasm from subarachnoid hemorrhage. Ultrasound has several advantages, notably that it is noninvasive, harmless (hence can be used repeatedly but caution is required in applying it to the globe), convenient because of the portability of the instrument, and inexpensive. More specific applications of this technique are discussed in Chap. 37, on developmental diseases of the nervous system, and in Chap. 33, on stroke. The related technique of echocardiography has also assumed a central role in the evaluation of stroke, as indicated in Chap. 33.


Neurology_Adams

Neurology_Adams. The electroencephalographic examination, for many years a standard laboratory procedure in the study of all forms of cerebral disease, has been supplanted by CT and MRI for the purposes of localization of structural lesions. It continues to be an essential part of the assessment of patients with seizures and those suspected of having seizures, as well as in brain death, and for the study of sleep (polysomnography) as described in the American Electroencephalographic Society Guideliness. It is also used in evaluating the encephalopathy of many systemic metabolic diseases and in the operating room to monitor cerebral activity in anesthetized patients. For a few diseases, such as Creutzfeldt-Jakob (prion) disease, it is a useful confirmatory laboratory test. The technique is described here in some detail, as its general use in neurology cannot suitably be assigned to any other single chapter.


Neurology_Adams

Neurology_Adams. The electroencephalograph records spontaneous electrical activity generated in the cerebral cortex. This activity reflects the electrical currents that flow in the extracellular spaces of the brain that are the summated effects of innumerable excitatory and inhibitory synaptic potentials upon cortical neurons. This spontaneous activity of cortical neurons is highly influenced and synchronized by subcortical structures, particularly the thalamus and high brainstem reticular formation. Efferent impulses from these deep structures are probably responsible for entraining cortical neurons to produce characteristic rhythmic brain-wave patterns, such as alpha rhythm and sleep spindles (see further on).


Neurology_Adams

Neurology_Adams. Electrodes, which are typically silver or silver-silver chloride discs 0.5 cm in diameter, are placed on the scalp using a conductive medium. The electroencephalograph has 8 to 32 or more amplifying units capable of recording from many areas of the scalp at the same time. The amplified brain rhythms are seen as waveforms of brain activity in the frequency range of 0.5 to 30 Hz (cycles per second) on a standard display that runs at 3 cm/s. In the past, the amplified signals were recorded on paper by a bank of pens but now, a digital format of the rhythms can be displayed on a computer screen and stored electronically. The favored configuration of electrode pairs, or montage, is the “International 10-20” system, which uses 10 electrodes on each side of the cranium and emphasizes contiguous regions of the brain for ease of visual inspection of the record (Fig. 2-7A).


Neurology_Adams

Neurology_Adams. The resulting electroencephalogram (EEG), essentially a voltage-versus-time graph, consists of a number of simultaneous parallel wavy lines, or “channels” (Fig. 2-7B). Each channel represents the difference in electrical potential between two electrodes (a common or ground electrode may be used as one recording site, but the channel still represents a bipolar recording). A positive voltage potential deflects the signal downward, and a negative one, upward by convention. The channels are arranged for viewing into standard montages that generally allow comparison of the activity from one region of the cerebral cortex to others, and particularly to the corresponding region of the opposite side.


Neurology_Adams

Neurology_Adams. Patients are usually examined with their eyes closed and while relaxed. Consequently, the ordinary EEG represents the electrocerebral activity that is recorded under restricted circumstances, usually during the waking or sleeping state, from several parts of the cerebral convexities during an almost infinitesimal segment of the person’s life. In addition to the resting record, a number of activating procedures are usually employed. First, the patient is asked to breathe deeply 20 times a minute for 3 min. Hyperventilation, through a mechanism yet to be determined, may activate characteristic seizure patterns or other abnormalities. Second, a powerful strobe light is placed about 15 inches from the patient’s eyes and flashed at frequencies of 1 to 20 per second with the patient’s eyes open and closed. In a healthy subject, the occipital EEG leads show waves corresponding to each flash of light (photic driving, Fig. 2-7C).


Neurology_Adams

Neurology_Adams. The EEG is recorded while the patient is drowsy and after the patient is allowed to fall asleep naturally or following the administration of sedative drugs. The drowsy state and the transition to and from deeper stages of sleep can reveal abnormalities. Many abnormalities associated with sleep are more evident with long-term, continuous EEG monitoring (hours to days) as described in Chap. 18. EEG activity can be synchronized with videographically recorded seizure activity in order to characterize the nature of a seizure. EEGs recorded by small digital devices or telemetry from freely moving ambulatory patients may be similarly useful in cases of suspected seizure disorders. Chapter 15 discusses these techniques in detail. Chapter 18 contains information on the use of EEG to analyze disorders of sleep (polysomnography).


Neurology_Adams

Neurology_Adams. Certain preparations are necessary if electroencephalography is to be most useful. The patient should not be sedated (except as noted above) and should not have been without food for a long time, for both sedative drugs and relative hypoglycemia may modify the normal EEG pattern and caffeine should be avoided if a sleep EEG study is planned. When dealing with patients who are suspected of having epilepsy and are already being treated for it, most physicians prefer to record the EEG while the patient continues to receive antiepileptic medications. During inpatient monitoring, these drugs are often withdrawn for a day or two in order to increase the likelihood of recording a seizure discharge but this requires careful clinical monitoring.


Neurology_Adams

Neurology_Adams. The interpretation of EEGs involves the recognition of several characteristic normal and abnormal patterns and background rhythms (in accordance with the age of the patient), the detection of asymmetries and periodic changes in rhythm, and, importantly, the differentiation of artifacts from genuine abnormalities (see Goldenshohn ES and Hughes JR).


Neurology_Adams

Neurology_Adams. The normal record in adults shows slightly asymmetrical 8to 12-per-second 50-mV sinusoidal alpha waves in both occipital and posterior parietal regions. These waves wax and wane in amplitude spontaneously and are attenuated or suppressed completely with eye opening or mental activity (see Fig. 2-7B). In contrast, the frequency of the alpha rhythm is almost invariant for an individual patient, although the rate slows with aging. Waves faster than 12 Hz and of lower amplitude (10 to 20 mV), called beta waves, are normally recorded from the frontal regions symmetrically. If benzodiazepines or other sedating drugs have been administered, an increase in the fast frequencies is typically observed. When the normal subject falls asleep, the alpha rhythm slows symmetrically and characteristic waveforms consisting of vertex sharp waves and sleep spindles appear (see Fig. 18-1). A small amount of theta (4to 7-Hz) activity may normally be present over the temporal regions, somewhat more so in


Neurology_Adams

Neurology_Adams. consisting of vertex sharp waves and sleep spindles appear (see Fig. 18-1). A small amount of theta (4to 7-Hz) activity may normally be present over the temporal regions, somewhat more so in persons older than 60 years of age. Delta (1to 3-Hz) activity is not present in the normal waking adult.


Neurology_Adams

Neurology_Adams. The presence of a photic driving response indicates that some of the visual pathways are preserved. Spread of the occipital response induced by photic stimulation, with the production of abnormal sharp or paroxysmal waves, provides evidence of abnormal cortical excitability (Fig. 2-7D). Seizure patterns may be produced during this type of EEG testing, accompanied by gross myoclonic jerks of the face, neck, and limbs (photomyoclonic response), by electrographic seizure activity that outlasts the photic stimulation (photoparoxysmal response), or by a convulsion (photoconvulsive response). Such effects occur often during periods of withdrawal from alcohol and other sedative drugs.


Neurology_Adams

Neurology_Adams. Children and adolescents are more sensitive than adults to all the activating procedures previously mentioned (see Blume and colleagues). It is customary for children to develop delta waves (3 to 4 Hz) during the middle and latter parts of a period of hyperventilation. This EEG activity, referred to as “breakdown,” or “buildup,” disappears soon after hyperventilation has stopped. The frequency of the dominant rhythms in infants is normally about 3 Hz, and they are very irregular. With maturation, there is a gradual increase in frequency and regularity of these occipital rhythms; an alpha rhythm appears by age 6 years and the adult frequency is reached by the age of 10 to 12 years (see Chap. 27 for further discussion of maturation of the brain as expressed in the EEG). The interpretation of records of infants and children require considerable experience because of the wide range of normal patterns at each age period (see Hahn and Tharp, Scher and Painter, and also Ebersole et al).


Neurology_Adams

Neurology_Adams. of records of infants and children require considerable experience because of the wide range of normal patterns at each age period (see Hahn and Tharp, Scher and Painter, and also Ebersole et al). Nevertheless, grossly asymmetrical records or seizure patterns are clearly abnormal in children of any age. Normal patterns in the fetus, from the seventh month onward, have been established. Certain changes in these patterns, as described by Stockard-Pope et al and by deWeerd, are indicative of a developmental disorder or disease.


Neurology_Adams

Neurology_Adams. Types of Abnormal Recordings Localized regions of greatly diminished or absent brain waves are seen overlying large area of cerebral infarction, traumatic necrosis, tumor, or extensive clot. These findings allow gross localization of the abnormality—but, of course, the nature of the lesion is not disclosed. Two types of abnormal waves, already mentioned, are of lower frequency and higher amplitude than normal. Waves below 4 Hz with amplitudes from 50 to 350 mV are called delta waves (Fig. 2-7E); those with a frequency of 4 to 7 Hz are called theta waves. Fast (beta) activity tends to be prominent frontally and usually reflects the effects of sedative drugs or, if focal, an immediately underlying skull defect called a “breach rhythm” (bone normally filters the abundant fast activity of the cortex).


Neurology_Adams

Neurology_Adams. Spikes are transient high-voltage waveforms that have a pointed peak at recording speeds and duration of 20 to 70 ms; a sharp waves is a similarly configured transient with a duration of 70 to 200 ms (Fig. 2-7F). Spikes or sharp waves that occur interictally are referred to as epileptiform discharges. At times, it is possible to infer localization from the reversal of the polarity of a sharp transient or spike in the EEG record. This “phase reversal” between two channels implies that the electrical activity originates near the site of the position of the common electrode (Fig. 2-7G, H).


Neurology_Adams

Neurology_Adams. The paroxysmal interruption of normal background EEG activity by a run of fast or slow waves is suggestive of seizures. When this paroxysmal discharge is composed of spikes and sharp waves, it signifies a seizure with greater certainty. The electrical discharges associated with absence seizures have a more stereotyped pattern of 3-per-second spike-and-wave complexes that characteristically appear abruptly in all leads of the EEG simultaneously and disappear almost as suddenly at the end of the seizure (Fig. 2-7I).


Neurology_Adams

Neurology_Adams. The absence of EEG activity, or “electrocerebral silence,” is a component of brain death but may be simulated by deep sedation with drugs or by profound hypothermia (Fig. 2-7J). Artifacts of various types should be apparent as the amplifier gains are increased; if not, there is a risk that the leads are not properly connected to the machine or of another technical fault. In the absence of nervous system depressants or extreme degrees of hypothermia, a record that is isoelectric (<2 uV except for artifacts) over all parts of the head is almost always a result of profound cerebral hypoxia, ischemia, massive cerebral hemorrhage or of trauma and raised intracranial pressure. Such a patient—without EEG activity, brainstem reflexes, and spontaneous respiratory or muscular activity of any kind—is said to be brain dead as discussed in Chap. 16.


Neurology_Adams

Neurology_Adams. Chap. 16. Epileptic seizures (see Chap. 15) are almost by definition associated with some abnormality in the EEG provided that it is being recorded at the time of the seizure. Rare exceptions are seizure states that originate in deep temporal, medial, or orbital frontal foci, from which the discharge fails to reach the scalp in sufficient amplitude to be seen against the normal background activity of the EEG. Most often, a completely normal EEG during a convulsion indicates a “pseudoseizure” (a psychogenic nonepileptic seizure, or “nonepileptic behavioral event”).


Neurology_Adams

Neurology_Adams. Some of the different types of seizure patterns are shown in Fig. 2-7F and I are associated with particular clinical syndromes in Chap. 16. The absence, myoclonic, and grand mal EEG patterns correlate closely with the clinical seizure type and may be present in milder form in the EEG during periods between clinically evident seizures (interictally). Seizures appear as generalized discharges throughout the cerebrum, or as localized to one region.


Neurology_Adams

Neurology_Adams. Between seizures, a single EEG recording will show a normal pattern in as many as 30 percent of patients with absence seizures and 50 percent of those with generalized tonic-clonic (grand mal) epilepsy (this percentage is less with repeated recordings). Antepileptic therapy may mask interictal EEG abnormalities but the extent to which this occurs is not known. The records of 30 to 40 percent of those with epilepsy, although abnormal between seizures, are nonspecifically so; consequently, the diagnosis of epilepsy can be made only by the correct interpretation of clinical data in relation to the EEG abnormality. Focal Brain Lesions (Brain Tumor, Abscess, Subdural Hematoma, Stroke, and Encephalitis)


Neurology_Adams

Neurology_Adams. Focal Brain Lesions (Brain Tumor, Abscess, Subdural Hematoma, Stroke, and Encephalitis) In a high proportion of patients, intracranial mass lesions are associated with focal or localized slow-wave activity (usually delta, as in Fig. 2-7E) or, occasionally, seizure activity. EEG is of considerable value in the diagnosis of herpes simplex encephalitis in which periodic high-voltage sharp waves and slow-wave complexes at intervals of 1 to 3 per second in the temporal regions are characteristic. The other encephalitides are also often associated with sharp or spike activity, particularly if there have been seizures. The EEG is particularly helpful in the diagnosis of prion disease as also noted below. Figure 2-7K shows the characteristic pattern of almost periodic sharp waves seen in Creutzfeldt-Jakob disease.


Neurology_Adams

Neurology_Adams. The EEG is now little used in the differential diagnosis of stroke, except to distinguish a transient ischemic attack from a seizure. In the past, one practical value was in the ability to differentiate an acute ischemic lesion in the distribution of the middle cerebral artery, which produces a large area of slowing, from lacunar infarction deep in the cerebrum or brainstem, in which the surface EEG is usually normal despite prominent clinical abnormalities. After 3 to 6 months, in roughly 50 percent of patients with infarction in the territory of the middle cerebral artery, the focal EEG slowing becomes normal. Perhaps half of these patients will have had normal EEGs even in the week or two following the stroke. A persistent abnormality is generally associated with a poor prognosis for further recovery. Large lesions of the diencephalon or midbrain produce bilaterally synchronous slow waves, but those of the pons and medulla (i.e., below the mesencephalon) are usually associated with


Neurology_Adams

Neurology_Adams. recovery. Large lesions of the diencephalon or midbrain produce bilaterally synchronous slow waves, but those of the pons and medulla (i.e., below the mesencephalon) are usually associated with a normal or near-normal EEG pattern despite catastrophic clinical changes.


Neurology_Adams

Neurology_Adams. A brief episode of cerebral concussion in animals produces focal EEG slowing similar to those described for cerebral infarction. Sharp waves or spikes sometimes emerge as the focal slow-wave abnormality resolves and these seizure-like changes may precede posttraumatic epilepsy; serial EEGs may be of value in this regard. During syncope, the EEG is slowed and of reduced amplitude even to the point of becoming “flat.” Upon recovery, a number of patterns have been described as discussed further in Chap. 17. Diseases That Cause Coma and States of Impaired Consciousness


Neurology_Adams

Neurology_Adams. Diseases That Cause Coma and States of Impaired Consciousness The EEG is abnormal in almost all conditions in which there is impairment of the level of consciousness. There is, for example, a fairly close correspondence between the severity of acute anoxic damage from cardiac arrest and the degree of EEG slowing. The mildest forms are associated with generalized theta activity, intermediate forms with widespread delta waves and the loss of normal background activity, and the most severe forms with “burst suppression,” in which brief isoelectric periods are followed by high-voltage sharp and irregular delta activity. The latter pattern usually progresses to the electrocerebral silence of brain death, a condition discussed earlier.


Neurology_Adams

Neurology_Adams. The term alpha coma refers to a unique EEG pattern in which an apparent alpha activity in the 8to 12-Hz range is distributed widely over the hemispheres rather than in its normal location posteriorly. When analyzed carefully, this background activity, unlike the normal monorhythmic alpha, is found to vary slightly in frequency. This is usually a transitional pattern after global anoxia; less often, alpha coma occurs with large acute pontine lesions. With severe hypothyroidism, the brain waves are normal in configuration but usually of decreased amplitude and frequency.


Neurology_Adams

Neurology_Adams. In altered states of alertness, the more profound the depression of consciousness, in general, the more abnormal and slower the EEG rhythms. In states of deep stupor or coma, the slow (delta) waves are bilateral and of high amplitude and tend to be more conspicuous over the frontal regions (Fig. 2-7L). This pertains in such differing conditions as acute meningitis or encephalitis and disorders that severely alter blood gases, glucose, electrolytes, and water balance; uremia; diabetic coma; and impairment of consciousness accompanying the large cerebral lesions discussed above. In hepatic coma, the degree of abnormality in the EEG corresponds roughly to the degree of confusion, stupor, or coma. Characteristics of hepatic coma are paroxysms of bilaterally synchronous large, sharp “triphasic waves” (Fig. 2-7L), although such waveforms may also be seen with less regularity in encephalopathies related to renal or pulmonary failure and with acute hydrocephalus (intermittent biphasic frontal


Neurology_Adams

Neurology_Adams. waves” (Fig. 2-7L), although such waveforms may also be seen with less regularity in encephalopathies related to renal or pulmonary failure and with acute hydrocephalus (intermittent biphasic frontal slowing is more typical of hydrocephalus).


Neurology_Adams

Neurology_Adams. An EEG may also be of help in the diagnosis of coma that is due to ongoing seizures (“nonconvulsive status epilepticus”) or, when the pertinent history is not available and there was an unobserved convulsion. It may also point to an otherwise unexpected cause of coma, such as hepatic encephalopathy, intoxication with barbiturates or other sedative-hypnotic drugs, the effects of diffuse anoxia–ischemia, catatonia, or hysteria (in which the EEG is normal).


Neurology_Adams

Neurology_Adams. Alzheimer disease and other degenerative diseases that cause serious impairment of cerebrocortical function are accompanied by relatively slight degrees of diffuse slow-wave abnormality in the theta (4to 7-Hz) range; many recordings are normal in the early and midstages of illness. More rapidly progressive disorders—such as subacute sclerosing panencephalitis (SSPE), Creutzfeldt-Jakob disease, and to a lesser extent the cerebral lipidoses—often have, in addition, very characteristic and almost pathognomonic EEG changes consisting of periodic bursts of high-amplitude sharp waves, usually bisynchronous and symmetrical (Fig. 2-7K). In a negative sense, a normal EEG in a patient who is profoundly apathetic is a point in favor of the diagnosis of hysteria, catatonia, or schizophrenia. Other Diseases of the Cerebrum


Neurology_Adams

Neurology_Adams. Other Diseases of the Cerebrum Many disorders of the brain cause little or no alteration in the EEG. Multiple sclerosis and other demyelinating diseases are examples, although as many as 50 percent of patients with advanced disease will have an abnormal record of nonspecific type (mild focal or diffuse slowing). Delirium tremens and Wernicke-Korsakoff disease, despite the dramatic nature of the clinical picture, cause little or no change in the EEG. Interestingly, the psychoses (bipolar disorders or schizophrenia), intoxication with hallucinogenic drugs such as lysergic acid diethylamide (LSD), and the majority of cases of mental retardation are associated either with no modification of the normal record or with only minor nonspecific abnormalities unless seizures are present. Clinical Significance of Minor Electroencephalogram Abnormalities


Neurology_Adams

Neurology_Adams. The gross EEG abnormalities discussed above are by themselves clearly abnormal, and any formulation of the patient’s clinical state should attempt to account for them. Lesser degrees of abnormality form a continuum between the undoubtedly abnormal and the completely normal and are of correspondingly less significance. Findings such as 14and 6-per-second positive spikes or small sharp waves during sleep, scattered 5or 6-per- second slowing, minor voltage asymmetries, and persistence of “breakdown” for a few minutes after hyperventilation are interpreted as normal variants or borderline abnormalities. Whereas borderline deviations in an otherwise entirely normal person have no clinical significance, the same minimal EEG findings associated with particular clinical signs and symptoms become important. The significance of a normal or “negative” EEG in certain patients suspected of having a cerebral lesion was discussed above.


Neurology_Adams

Neurology_Adams. As a general clinical principle, the results of the EEG, like those of the EMG and electrocardiogram, are meaningful only in relation to the illnesses under consideration and to the clinical state of the patient at the time the recordings were made.


Neurology_Adams

Neurology_Adams. The stimulation of sense organs or peripheral nerves evokes an electrical response in the corresponding cortical receptive areas and in a number of subcortical relay stations. However, one cannot place a recording electrode near the nuclear relay stations, nor can one detect tiny potentials of only a few microvolts among the much larger background activity in the EEG. The use of computerized averaging methods, introduced by Dawson in 1954, has provided a means of overcoming these problems. Initially, emphasis was on the study of late waves (over 100 ms after the stimulus) because they are of high amplitude and easy to record. However, there is more clinical utility in recording the much smaller, short-latency waveforms, which are received at each nuclear relay within the main sensory systems. These waveforms are maximized by the computer to a point where their latency and voltage can easily be measured. One of the remarkable properties of evoked potentials is their resistance to


Neurology_Adams

Neurology_Adams. systems. These waveforms are maximized by the computer to a point where their latency and voltage can easily be measured. One of the remarkable properties of evoked potentials is their resistance to anesthesia, sedative drugs, and in states of reduced consciousness such as hypoxic-ischemic encephalopathy. This permits their use for monitoring the integrity of cerebral pathways in situations that limit the value of the EEG.


Neurology_Adams

Neurology_Adams. The interpretation of evoked potentials (visual, auditory, and somatosensory) is based on the prolongation of the latencies of the waveforms after the stimulus, the interwave latencies, and asymmetries in timing. Norms for latencies have been established, but it is advisable to confirm these in each laboratory. Typically 2.5 or 3 standard deviations above the mean latency for any measurement is taken as the definition of abnormality (Table 2-4). The amplitudes of the waves are less informative for clinical work.


Neurology_Adams

Neurology_Adams. For many years it had been known that a light stimulus flashing on the retina evokes a discernible waveform over the occipital lobes. In the EEG, such responses to fast rates of stimulation are referred to as the occipital driving response (Fig. 2-7C). It is also appreciated that a visual evoked response is produced by the sudden change of a viewed checkerboard pattern. These responses, produced by rapidly reversing the pattern of black and white squares, are easier to detect and to measure than are flash responses and are more consistent in waveform from one individual to another. The pattern shift stimulus, applied first to one eye and then to the other, can demonstrate conduction delays in the visual pathways of patients who have had disease of the optic nerve—even when there are no residual signs of reduced visual acuity, visual field abnormalities, alterations of the optic nerve head, or changes in pupillary reflexes. Furthermore, the presence of a normal visual evoked response


Neurology_Adams

Neurology_Adams. signs of reduced visual acuity, visual field abnormalities, alterations of the optic nerve head, or changes in pupillary reflexes. Furthermore, the presence of a normal visual evoked response suggests that blindness is not due to a lesion in the anterior visual pathways and their projections to the occipital cortex, for example, in hysterical blindness. Figure 2-8 illustrates the normal pattern shift visual evoked response (PSVER) and two types of delayed responses. Reductions in the amplitude and duration of PSVER usually accompany prolonged latencies but are difficult to quantify. By presenting the pattern-shift stimulus to one hemifield, it is possible to isolate a lesion to an optic tract or radiation, or one occipital lobe, but with much less precision than that provided by the usual monocular testing.


Neurology_Adams

Neurology_Adams. The expected latency for the positive wave, by convention a downward deflection, is near 100 ms (thus the term P100 has also been used to designate the waveform); an absolute latency from the stimulus longer than 118 ms or a difference in latencies of greater than 9 ms between the two eyes signifies involvement of one optic nerve (see Table 2-4). Bilateral prolongation of latencies, demonstrated by separate stimulation of each eye, can be caused by lesions in both optic nerves, the optic chiasm, or the visual pathways posterior to the chiasm.


Neurology_Adams

Neurology_Adams. As indicated above, PSVER is especially valuable in proving the existence of active or residual disease of an optic nerve. Patients with previous optic neuritis almost invariably have prolonged latencies. Furthermore, prolongations of PSVER are found in about one-third of multiple sclerosis patients who have had no history or clinical evidence of optic nerve involvement. This acquires significance in that the finding of abnormal PSVER in a patient with a clinically apparent demyelinating lesion elsewhere in the CNS may usually be taken as evidence of multiple sclerosis, as discussed in Chap. 37.


Neurology_Adams

Neurology_Adams. A compressive lesion of an optic nerve will have the same effect as a primarily demyelinating one. Many other diseases of the optic nerves—including toxic and nutritional amblyopias, ischemic optic neuropathy, and the Leber type of hereditary optic neuropathy—show abnormalities of the PSVER. Glaucoma and other diseases of the eye, if severe enough to affect the optic nerve, may also produce increased latencies. Impaired visual acuity has little effect on the latency but does correlate well with the amplitude of the PSVER (a property that is exploited in some computerized testing for visual acuity).


Neurology_Adams

Neurology_Adams. The effects of auditory stimuli can be studied in the same way as visual ones by a procedure called brainstem auditory evoked responses, or potentials (BAERs, or BAEPs). Between 1,000 and 2,000 clicks, delivered first to one ear and then to the other, are recorded through scalp electrodes and superimposed on each other by computer and thereby maximized. A series of seven waves appears at the scalp within 10 ms after each stimulus. On the basis of depth recordings and the study of lesions produced in cats as well as pathologic studies of the brainstem in disease, it has been established that each of the first five waves is generated by a specific brainstem structure, as indicated in Fig. 2-9. The generators of waves VI and VII in particular are uncertain. The presence of wave I and its absolute latency test the integrity of the auditory nerve.


Neurology_Adams

Neurology_Adams. Clinical interpretations of BAERs are based mainly on latency measurements from the stimulus and interwave latencies. The most important are the interwave latencies between I and III, and III and V (see Table 2-4). A lesion that affects one of the auditory nuclear relay stations or its immediate connections manifests itself by a delay in the appearance or an absence of all subsequent waves; in other words, the nuclei behave as if they are connected in series. These effects are more pronounced on the side of the stimulated ear than contralaterally. This is difficult to understand, as a majority of the cochlear-superior olivary-lateral lemniscal-medial geniculate fibers cross to the opposite side. It is also surprising that a lesion of one relay station would allow impulses, even though delayed, to continue their ascent and be recordable in the cerebral cortex.


Neurology_Adams

Neurology_Adams. BAERs are a particularly sensitive means of detecting lesions of the eighth cranial nerve (vestibular schwannoma and other tumors of the cerebellopontine angle) and of the auditory pathways of the brainstem. Almost one-half of patients with definite multiple sclerosis and a lesser number with a possible or probable diagnosis of this disease will show abnormalities of the BAERs, (usually a prolongation of interwave latencies I to III or III to V), even in the absence of clinical symptoms and signs of brainstem disease. The BAERs are also useful in assessing hearing in infants who have been exposed to ototoxic drugs, in young children who cannot cooperate with audiometry, and in those with psychogenic or feigned deafness.


Neurology_Adams

Neurology_Adams. The technique consists of applying 5-per-second painless transcutaneous electrical stimuli to the median, peroneal, or tibial nerves and recording the evoked potentials (for the upper limb) sequentially as they pass the brachial plexus over the Erb point above the clavicle, over the C2 vertebra, and over the opposite parietal cortex, and (for the lower limb) over the lumbar roots of the cauda equina, the nuclei over the cervical spine, and the opposite parietal cortex. The impulses generated in large touch fibers by 500 or more stimuli and averaged by computer can be traced through the corresponding peripheral nerves, spinal roots, and posterior columns to the cuneate and gracile nuclei in the lower medulla, through the medial lemniscus to the contralateral thalamus, and thence to the sensory cortex of the parietal lobe. Delay between the stimulus site and the Erb point or the lumbar spine indicates peripheral nerve disease; delay from the Erb point (or lumbar spine) to C2 implies an


Neurology_Adams

Neurology_Adams. cortex of the parietal lobe. Delay between the stimulus site and the Erb point or the lumbar spine indicates peripheral nerve disease; delay from the Erb point (or lumbar spine) to C2 implies an abnormality in the appropriate nerve roots or, more frequently, in the posterior columns; the presence of lesions in the medial lemniscus and thalamoparietal pathway can be inferred from delays of subsequent waves recorded from the parietal cortex (Fig. 2-10).


Neurology_Adams

Neurology_Adams. The normal waveforms are designated by the symbols P (positive) and N (negative), with a number indicating the interval of time in milliseconds from stimulus to recording (e.g., N11, N13, P13, P22, etc.). As shorthand for the polarity and approximate latency, the summated wave that is recorded at the cervicomedullary junction is termed N/P13, and the cortical potential from median nerve stimulation seen in two contiguous waves of opposite polarity is called N19–P22. The corresponding cortical wave after tibial or peroneal nerve stimulation is called N/P37. Each trace is the averaged response to 1,024 stimuli; the superimposed trace represents a repetition to demonstrate waveform consistency.


Neurology_Adams

Neurology_Adams. For purposes of clinical interpretation, the generators of the SEP waves are assumed to be linked in series, so that an interwave prolongation in latency indicates a conduction defect between the generators of the two peaks involved (Chiappa and Ropper). Normal values are shown in Table 2-4. Recordings with pathologically verified lesions at these levels are to be found in the monograph by Chiappa. This test has been most helpful in establishing the existence of lesions in spinal roots, posterior columns, and brainstem in disorders such as the ruptured lumbar and cervical discs, multiple sclerosis, and lumbar and cervical spondylosis when the clinical data are uncertain. The cerebral counterpart also pertains—namely, that obliteration of the cortical waves (assuming that all preceding waves are unaltered) reflects profound damage to the somatosensory pathways in the hemisphere or to the cortex itself. For example, the bilateral absence of cortical somatosensory waves after cardiac


Neurology_Adams

Neurology_Adams. waves are unaltered) reflects profound damage to the somatosensory pathways in the hemisphere or to the cortex itself. For example, the bilateral absence of cortical somatosensory waves after cardiac arrest is a powerful predictor of a poor clinical outcome; the persistent absence of a cortical potential on one side after stroke usually indicates such profound damage that only a limited clinical recovery is to be expected.


Neurology_Adams

Neurology_Adams. Evoked potential techniques have also been used in the experimental study of olfactory and trigeminal sensation (see Chap. 11). Magnetic Stimulation of the Motor System


Neurology_Adams

Neurology_Adams. It is possible, by using single-pulse high-amplitude magnetic stimulation, to directly activate the motor cortex (transcranial magnetic stimulation) and cervical spine segments, and to detect delays or lack of conduction in descending motor pathways. This technique, introduced by Marsden and associates, painlessly stimulates only the largest motor neurons (presumably Betz cells) and the fastest-conducting axons. Cervical magnetic stimulation is believed to activate the anterior roots. The difference in time between the motor cortical and cervical activation of hand or forearm muscles reflects the conduction velocity of the cortical–cervical cord motor neurons. The technique has been used to understand the organization, function, and recovery of the motor cortex and the pathophysiology of stroke, multiple sclerosis, and amyotrophic lateral sclerosis. Although the degree of functional deficit does not precisely correlate with the degree of electrophysiologic change, one expects that


Neurology_Adams

Neurology_Adams. of stroke, multiple sclerosis, and amyotrophic lateral sclerosis. Although the degree of functional deficit does not precisely correlate with the degree of electrophysiologic change, one expects that refinements of this technique may be useful in evaluating the status of the corticospinal motor system as well as other cortically based functions.


Neurology_Adams

Neurology_Adams. It is also possible to activate the motor (anterior) roots by magnetic stimulation and to measure the time required to elicit a muscle contraction (see review by Cros and Chiappa). These root stimulation tests can be quite uncomfortable for the patient as a result of the contraction of muscles surrounding the stimulation site. This technique finds its main use in diseases of the motor neuron, roots, and plexus.


Neurology_Adams

Neurology_Adams. Among the very late brain electrical potentials (>100-ms latency) that can be extracted from background activity by computer methods, are a group that cannot be classified as sensory or motor but rather as psychophysical responses to environmental stimuli. These responses are of very low voltage, often fleeting and inconsistent, and of unknown anatomic origin. The most studied types occur approximately 300 ms (P300) after an attentive subject identifies an unexpected or novel stimulus that has been inserted into a regular train of stimuli. Almost any stimulus modality can be used and the potential occurs even when a stimulus has been omitted from a regular pattern. The amplitude of the response depends on the difficulty of the task and has an inverse relationship to the frequency of the unexpected or “odd” event; the latency depends on the task difficulty and other features of testing. There is therefore no single P300; instead, there are numerous types, depending on the experimental


Neurology_Adams

Neurology_Adams. or “odd” event; the latency depends on the task difficulty and other features of testing. There is therefore no single P300; instead, there are numerous types, depending on the experimental paradigm. Prolongation of the latency is found with aging and in dementia as well as with degenerative diseases such as Parkinson disease, progressive supranuclear palsy, and Huntington chorea. The amplitude is reduced in schizophrenia and depression. The potential has been interpreted by some as a reflection of the subject’s orienting behavior or attention and by others, including Donchin, who discovered the phenomenon, as related to an updating of the brain’s representation of the environment. The P300 remains a curiosity for the clinical neurologist because abnormalities are detected only when large groups are compared to normal individuals, and the technique is not as standardized as the conventional evoked potentials. A review of the subject can be found in sections by Altenmüller and Gerloff


Neurology_Adams

Neurology_Adams. groups are compared to normal individuals, and the technique is not as standardized as the conventional evoked potentials. A review of the subject can be found in sections by Altenmüller and Gerloff and by Polich in the Niedermeyer and Lopes DaSilva text on electroencephalography.


Neurology_Adams

Neurology_Adams. It was long ago discovered that muscle would contract when a pulse of electric current was applied to the skin, near the point of entrance of the muscular nerve (the motor point). The electrical pulse required is brief, less than a millisecond, and is most effectively induced by rapidly alternating (faradic) current. If there has been muscle denervation, an electrical pulse of several milliseconds induced by a constant electrical (galvanic) stimulus is required to produce the same response. For decades, this was the standard electrical method for evaluating denervation of muscle. Although still valid, it was replaced by nerve conduction studies and by the needle electrode examination. The latter test, based on the sherringtonian concept of the “motor unit” described in Chap. 3, is accomplished by the insertion into muscle of needle electrodes to measure spontaneous and voluntarily evoked muscle fiber activity. The terms electromyography and electromyogram were used originally to


Neurology_Adams

Neurology_Adams. by the insertion into muscle of needle electrodes to measure spontaneous and voluntarily evoked muscle fiber activity. The terms electromyography and electromyogram were used originally to describe the needle electrode examination but are now a common shorthand designation for the entire electrodiagnostic evaluation, including the nerve conduction studies.


Neurology_Adams

Neurology_Adams. The main laboratory technique for the study of peripheral nerve function involves the transcutaneous stimulation of motor or sensory nerves and recording of the elicited action potentials in the muscle (CMAP) and the sensory nerve action potential (SNAP). The results of these motor and sensory nerve conduction studies, expressed as amplitudes, conduction velocities, and distal latencies, yield certain quantitative information and additional qualitative observations regarding the waveform of electrical neural and muscular impulses.


Neurology_Adams

Neurology_Adams. Hodes and coworkers, in 1948, were the first to describe nerve conduction studies in patients, and the techniques used currently are not much changed. An accessible nerve is stimulated through the skin by surface electrodes, using a stimulus that is large enough to recruit (cause a discharge in) all the available nerve fibers. The resulting action potential is recorded by electrodes on the skin (1) over the muscle distally in the case of motor fibers stimulated in a mixed or motor nerve (CMAP), (2) over the nerve more distally, using antidromic techniques for sensory nerve conduction studies (this has technical advantages over orthodromic techniques), and (3) over the nerve more proximally for mixed (sensory and motor) nerve conduction studies. These techniques are the ones used most often in clinical work. An alternative but much more demanding experimental technique uses “near-nerve” needle electrodes to record action potentials as they course through the nerve. The main


Neurology_Adams

Neurology_Adams. most often in clinical work. An alternative but much more demanding experimental technique uses “near-nerve” needle electrodes to record action potentials as they course through the nerve. The main characteristics of the conventional nerve conduction studies are described below.


Neurology_Adams

Neurology_Adams. The peak amplitude of the evoked muscle action potential to a maximal stimulus (CMAP) yields valuable information about peripheral nerve function. The amplitude, usually in the order millivolts, reflects the summated electrical potential generated by the depolarization of a muscle innervated by the motor nerve (Fig. 2-11). In instances of disease, the amplitude is a semiquantitative measure of the number of remaining normal nerve fibers and of the innervated volume of muscle. It is usually possible to obtain a reliable motor conduction study as long as some functioning nerve fibers remain intact, although the compound muscle potential recorded may be very low. The latency to the CMAP waveform is the basis for calculations of motor nerve conduction velocity. Reduction in motor amplitudes is a specific and sensitive indicator of axonal loss. Demyelinative lesions affecting the large, fast-conducting fibers also reduce the peak summated amplitude of the CMAP but are the result of


Neurology_Adams

Neurology_Adams. is a specific and sensitive indicator of axonal loss. Demyelinative lesions affecting the large, fast-conducting fibers also reduce the peak summated amplitude of the CMAP but are the result of differential arrival times of the electrical potentials from each axon at the muscle. Table 2-5 shows the range of normal amplitudes for the CMAPs that are elicited by stimulation of the main motor nerves.


Neurology_Adams

Neurology_Adams. The conduction times that are utilized in clinical work are the latency from the stimulus artifact to the onset of the compound muscle action potential (CMAP), the distal (or terminal) latency; and from the stimulus to the peak of the CMAP, peak motor latency (see Fig. 2-11). A stimulus is then applied to the nerve at a second site more proximally, and a conduction time can be measured over a longer segment of nerve. When the distance (in millimeters) between the two sites of stimulation is divided by the difference in the distal latencies (in milliseconds), one obtains a conduction velocity (in meters per second). This method isolates the conduction time across a segment of a peripheral nerve by eliminating the transmission time across the neuromuscular junction and the duration of muscle depolarization. Motor nerve conduction velocity represents the maximal velocity of propagation of the action potentials in the largest-diameter and fastest- conducting nerve fibers. These velocities


Neurology_Adams

Neurology_Adams. depolarization. Motor nerve conduction velocity represents the maximal velocity of propagation of the action potentials in the largest-diameter and fastest- conducting nerve fibers. These velocities in normal subjects vary from a minimum of 40 or 45 m/s to a maximum of 65 to 75 m/s, depending upon which nerve is studied (e.g., slower in the legs than in the arms; see Table 2-5). Values are lower in infants, reaching the adult range by the age of 2 to 4 years, and declining again slightly with advancing age. Conduction velocity also is diminished with exposure to cold, a potentially important factor if these recordings are taken when the patient’s skin is cool; consequently, measurement of skin temperature is routinely done prior to performing the nerve conduction tests.


Neurology_Adams

Neurology_Adams. Normal values have been established for distal latencies from the usual sites of stimulation on various mixed nerves to the appropriate muscles. Stimulating the median nerve at the wrist, for example (see electrode 1 and segment A in Fig. 2-11), has a latency for motor conduction through the carpal tunnel to the median-innervated thenar muscles of less than approximately 4.5 ms in healthy adults. Similar normal values have been compiled for orthodromic and antidromic sensory conduction velocities and for distal latencies in all the main peripheral nerves (see Table 2-5).


Neurology_Adams

Neurology_Adams. The main effect of disease processes that preferentially injure axons, as mentioned above, is a reduction in the CMAP amplitude (Fig. 2-12B). However, some processes affect the fastest-conducting, large-diameter fibers and also usually reduce the conduction velocity because the remaining thinner fibers conduct more slowly. In most neuropathies, all the axons are affected either by a fairly uniform “dying-back” phenomenon or by wallerian degeneration as described in Chap. 43, and nerve conduction velocities are then less affected. This is true, for example, in typical alcoholic-nutritional, carcinomatous, uremic, diabetic, and other metabolic neuropathies, in which conduction velocities range from the low-normal range to mildly slowed. By contrast, demyelinating neuropathies (see Chap. 46) show marked slowing of conduction and, in the case of the acquired demyelinating diseases, there is also dispersion of the motor action potential and a characteristic conduction block (Fig. 2-12C).


Neurology_Adams

Neurology_Adams. The sensory nerve action potential (SNAP) is far lower in amplitude than the CMAP. It directly represents the action potentials in a group of sensory nerve axons. When one attempts to measure sensory nerve action potentials, the summation of electrical activity provided by many motor units discharging at the muscle is not available and electronic amplification is required. In contrast to motor conduction measurements, the nerve is typically stimulated at one site and recordings are performed at two distal sites (therefore antidromically for sensory conduction) in order to obtain both the amplitude (at the more proximal site) and conduction velocity by the subtraction method (Fig. 2-13). Sensory potentials, measured in microvolts, are sometimes very small or absent and sensory conduction measurements may then be difficult to determine. Table 2-5 gives the range of normal values for sensory nerve action potential amplitudes and velocities.


Neurology_Adams

Neurology_Adams. By stimulating a motor nerve at multiple sites along its course, it is possible to demonstrate segments in which conduction is partially “blocked” or is differentially slowed. From such data one infers the presence of a multifocal demyelinative process in motor nerves. This contrasts with the findings in certain of the inherited and metabolic demyelinating neuropathies, in which all parts of the nerve fiber are altered to more or less the same degree, that is, there is uniform slowing and reduction in amplitude and no conduction block.


Neurology_Adams

Neurology_Adams. As a technical matter, conduction block is demonstrated by a reduction in the amplitude of the CMAP elicited from the proximal site along the motor nerve, compared to stimulation at a distal site. Generally, a 40 percent reduction in amplitude over a short distance of nerve, or 50 percent over a longer distance, qualifies as a block, one possible exception being along the tibial nerve, in which there is some degree of physiologic dispersion; therefore, a slight drop in amplitude over the length of the nerve is normally expected. It is important to be sure that any reduction in amplitude along the course of the nerve is not solely a result of dispersion of the waveform as mentioned previously. The presence of a conduction block can also be inferred from the finding of poor recruitment of muscle action potentials and the concurrent absence of active denervation (see further on). The finding of conduction block is a main feature of a number of acquired immune demyelinating neuropathies,


Neurology_Adams

Neurology_Adams. action potentials and the concurrent absence of active denervation (see further on). The finding of conduction block is a main feature of a number of acquired immune demyelinating neuropathies, including Guillain-Barré syndrome, chronic inflammatory demyelinating neuropathy, and multifocal conduction block associated with the GM1 antibody, which are discussed in


Neurology_Adams

Neurology_Adams. Chap. 46. Focal conduction block may be caused simply by nerve compression at certain common sites (fibular head, across the elbow, flexor retinaculum at the wrist, etc.) rather than to an intrinsic disease of the peripheral nerves. Focal compression of nerve, as occurs in these entrapment syndromes, produces localized slowing or blocks in conduction, perhaps because of segmental demyelination at the site of compression. The demonstration of such localized changes of conduction affords ready confirmation of nerve entrapment; for example, if the distal latency of the median nerve (Fig. 2-11A) exceeds 4.5 ms while that of the ulnar nerve remains normal, compression of the median nerve in the carpal tunnel is likely. Similar focal slowing or partial block of conduction may be recorded from the ulnar nerve at the elbow and from the peroneal nerve at the fibular head.


Neurology_Adams

Neurology_Adams. The examiner should also be aware of a normal variant, the Martin-Gruber anastomosis that exists in close to 20 percent of individuals; in this configuration, axons from the median nerve cross into the ulnar nerve in the mid-forearm to innervate normally ulnar associated muscles in the hand. Distal stimulation of the ulnar nerve then gives higher amplitude ulnar CMAP than proximal stimulation, simulating conduction block, but without weakness or atrophy. The anastomosis can be demonstrated by obtaining a normal CMAP when stimulating the proximal median nerve and recording over ulnar innervated muscles. Information about the conduction of impulses through the proximal segments of a nerve, including the spinal roots, is provided by the study of the H reflex and the F wave (Fig. 2-14).


Neurology_Adams

Neurology_Adams. H reflex In 1918, Hoffmann, after whom the H reflex was named, showed that submaximal stimulation of mixed motor–sensory nerves induces a muscle contraction (H wave, Fig. 2-14A) after a latency that is far longer than that of the direct motor response. This reflex, the electrical representation of the ankle jerk, is based on the activation of afferent fibers from muscle spindles (the same axons that conduct the afferent volley of the tendon reflex). Thus the long delay, typically 28 to 35 ms after the stimulus (adjusted for height and age), reflects the cumulative time required for the impulses to reach the spinal cord via the sensory fibers, synapse with anterior horn cells, and to be transmitted along motor fibers to the muscle (see Fig. 3-1). The H reflex is a useful measure because the impulse traverses both the posterior and anterior spinal roots. The H reflex is particularly helpful in the diagnosis of S1 radiculopathy and of polyradiculopathies. It is difficult to obtain an H


Neurology_Adams

Neurology_Adams. impulse traverses both the posterior and anterior spinal roots. The H reflex is particularly helpful in the diagnosis of S1 radiculopathy and of polyradiculopathies. It is difficult to obtain an H reflex from nerves other than the tibial. Stimuli of increasing frequency but low intensity cause a progressive depression and finally obliteration of H waves. In parallel with the Achilles tendon reflex, the H-reflex is transiently obliterated in spinal shock (see Chap. 42).


Neurology_Adams

Neurology_Adams. F response (wave) The F response, so named because it was initially elicited in the feet, was first described by Magladery and McDougal in 1950. It is evoked by a supramaximal stimulus of a mixed motor–sensory or pure motor nerve (Fig. 2-14B). After a latency substantially longer than for the CMAP, a second small muscle action potential is normally recorded at 28 to 32 ms in arms and 40 to 58 ms in legs. This F wave is the result of impulses that travel antidromically in motor fibers to the anterior horn cells, a small number of which are activated and produce an orthodromic response that is recorded in a distal muscle. The F response is representative of proximal motor nerve and root conduction in that it traverses only the ventral root and can be elicited from a number of muscles.


Neurology_Adams

Neurology_Adams. Both responses are lost or delayed in some severe and generalized polyneuropathies (see Chap. 43). The combination of a normal F response and an absent H reflex is found in diseases of sensory nerves and roots. As with the H reflex, the F wave may be absent in the state of spinal shock or destructive diseases of the spinal cord (see Chap. 42). Both of these “late responses” find their main use as corroborative tests that are interpreted in the context of the entire nerve conduction examination.


Neurology_Adams

Neurology_Adams. Blink responses This special nerve conduction test is not in frequent clinical use but it serves a purpose in the diagnosis of certain demyelinating neuropathies and in any process that affects the trigeminal or facial nerve. The supraorbital (or infraorbital) nerve is stimulated transcutaneously and the reflex closure of both orbicularis oculi muscles is recorded with surface electrodes. Two CMAP bursts generated by facial motor neurons are observed: the first (R1) appears ipsilaterally 10 ms after the stimulus and the second (R2), ipsilaterally at 30 ms and contralaterally up to 5 ms later. The amplitudes of the responses vary considerably and are not in themselves clinically important. The first response is not visible as a muscular contraction but may serve some preparatory function by shortening the blink reflex delay. R1 is mediated by an oligosynaptic pontine circuit consisting of one to three neurons located in the vicinity of the principal sensory nucleus of the trigeminal


Neurology_Adams

Neurology_Adams. by shortening the blink reflex delay. R1 is mediated by an oligosynaptic pontine circuit consisting of one to three neurons located in the vicinity of the principal sensory nucleus of the trigeminal nerve; R2 uses a broader and less-well-defined reflex pathway in the pons and medulla.


Neurology_Adams

Neurology_Adams. The pattern of abnormalities of the R1 and R2 responses assist in localizing a lesion to the afferent trigeminal nerve, the efferent facial nerve, or the interneurons in the pons. In Bell palsy there is a delay or absence of R1 and R2 responses only on the affected side. Large acoustic neuromas (vestibular schwannomas) also may interfere with the efferent portion of the response. The test may be helpful in identifying a demyelinating neuropathy when the facial and oropharyngeal muscles are affected. Diseases of the brainstem have yielded inconsistent responses. It is noteworthy that the test is normal in patients with trigeminal neuralgia. Chap. 46)


Neurology_Adams

Neurology_Adams. Chap. 46) This test of the neuromuscular junction is based on Jolly’s observation in 1895 that in myasthenia gravis the strength of muscular contractions progressively declines in response to a train of stimuli. By adjusting the amplitude of a stimulus over a nerve to the supramaximal range, a maximal CMAP may be obtained for each stimulus. With repeated stimuli, each response will have the same waveform and amplitude. In a healthy individual, a muscular response follows each stimulus with rates of stimulation up to 25 per second for periods of 60 s or more before a decrement of the CMAP appears. A decrement of 10 percent or more denotes a failure of a proportion of the neuromuscular junctions.


Neurology_Adams

Neurology_Adams. In certain disorders, notably myasthenia gravis, a train of 4 to 10 stimuli at rates optimally 2 to 3 per second, the amplitude of the motor potentials decreases (Fig. 2-15A). A progressive reduction in amplitude is most likely to be found in proximal muscles, but these are not easily stimulated for which reason the locations most commonly used for clinical testing are the accessory nerve in the posterior triangle of the neck (trapezius), the ulnar nerve (hypothenar muscle), the median nerve at the wrist (thenar muscle), and the facial nerve (orbicularis oculi muscle).


Neurology_Adams

Neurology_Adams. The sensitivity of the procedure is improved by first exercising the tested muscle for 30 to 60 s; a form of post-tetanic potentiation. The full procedure consists of testing the muscle with a train of stimuli before and immediately after exercise (or maximal voluntary contraction) and at 30-s intervals for several minutes. The posttetanic potentiation at first partially compensates for the depletion of ACh during slow rates of stimulation; this is followed by an exaggerated decrease in the transmission through the neuromuscular junction during the approximately 2 to 4 min after exercise. The induced failure of neuromuscular transmission in myasthenia is similar to the one produced by curare and other nondepolarizing neuromuscular blocking agents, and the electrical features of both can be partially corrected with anticholinesterase drugs such as neostigmine and edrophonium. Similar but lesser decremental responses may occur in poliomyelitis, ALS, and certain other diseases of the


Neurology_Adams

Neurology_Adams. be partially corrected with anticholinesterase drugs such as neostigmine and edrophonium. Similar but lesser decremental responses may occur in poliomyelitis, ALS, and certain other diseases of the motor unit or motor nerve, particularly those resulting in the growth of reinnervating nerve twigs.


Neurology_Adams

Neurology_Adams. The Lambert-Eaton myasthenic syndrome, sometimes associated with oat cell carcinoma of the lung, as discussed in Chap. 46, is characterized by a presynaptic blockage of acetylcholine release and, with rapid rates of stimulation, produces the opposite effect on neuromuscular transmission to the one recorded in myasthenia gravis. There is instead an increment in the amplitude of the CMAP with continued stimulation. During very rapid repetitive stimulation (20to 50-per-second), the muscle action potentials, which are small or practically absent with the first stimulus, increase in voltage with each successive response until a more nearly normal amplitude is attained (see Fig. 2-15B). Exercising the muscle for 10 s before stimulation will cause a posttetanic facilitation in patients with the Lambert-Eaton syndrome (200-fold increases are not uncommon). A less important decremental response to slow stimulation may occur, but it is difficult to discern because of the greatly diminished


Neurology_Adams

Neurology_Adams. the Lambert-Eaton syndrome (200-fold increases are not uncommon). A less important decremental response to slow stimulation may occur, but it is difficult to discern because of the greatly diminished amplitude of the initial responses. The effects of botulinum toxin and of aminoglycoside antibiotics are similar, that is, being active at the presynaptic membrane, they produce an incremental response at high rates of stimulation.


Neurology_Adams

Neurology_Adams. The single-fiber EMG, discussed in a later section, is an even more sensitive method of detecting failure of the neuromuscular junction. Needle Examination of Muscle (Electromyography)


Neurology_Adams

Neurology_Adams. In the usual EMG examination, a plan for the study is made based on detailed knowledge of muscular innervation and focusing on the regions affected by weakness. In some patients, as in those with motor neuron diseases or polymyositis, a wider sampling of muscles is required to detect changes in asymptomatic regions. This technique requires the use of monopolar or concentric bipolar needle electrodes, which are inserted into the body of the muscle to record the electrical activity generated by contraction. With concentric electrodes, the tip of the wire that runs in the hollow of the needle is in proximity to many muscle fibers belonging to several different overlapping motor units; this is the active recording electrode. The shaft of the needle, in contact over most of its length with intercellular fluid and many other muscle fibers, serves as the reference electrode. Monopolar electrodes use the uninsulated needle tip as the active electrode, while the reference electrode may be


Neurology_Adams

Neurology_Adams. intercellular fluid and many other muscle fibers, serves as the reference electrode. Monopolar electrodes use the uninsulated needle tip as the active electrode, while the reference electrode may be another monopolar needle electrode placed elsewhere in subcutaneous tissue or a surface electrode on the skin overlying the muscle. Patients almost invariably find this portion of the test uncomfortable and should be prepared by a description of the procedure. Rapid and brief needle insertion by the skilled examiner makes the test more tolerable.


Neurology_Adams

Neurology_Adams. As the electrical impulse travels along the surface of the muscle toward the recording electrode, a positive potential is recorded on the oscilloscope, that is, the recorded signal is deflected downward by convention (at A in Fig. 2-16). When the depolarized zone moves under the recording electrode, it becomes relatively negative and the recorded signal is deflected upward (at B). As the depolarized zone continues to move along the sarcolemma, away from the recording electrode, the current begins to flow outward through the membrane toward the distant depolarized region, and the recording electrode becomes relatively positive again (at C). There is then a return to the resting isopotential position. The net result is a triphasic action potential, as in Fig. 2-16. This configuration is typical of the firing of a single fiber.


Neurology_Adams

Neurology_Adams. The electrical activity of various muscles is recorded both at rest and during active contraction by the patient. Muscle fibers do not normally discharge until activated together in motor unit activity. This involves the almost simultaneous contraction of all the muscle fibers innervated by a single anterior horn cell. Although the typical configuration of a motor unit potential (MUP) is triphasic, up to 10 percent of normal MUPs consist of four or more phases (polyphasic potentials); however, an excess of polyphasic potentials beyond this is pathologic.


Neurology_Adams

Neurology_Adams. Normal muscle in the resting state should be electrically silent; the small tension spoken of as muscle tone has no EMG equivalent. There are, however, two closely related types of normal spontaneous activities and another that is induced by the insertion of the needle itself. One is a low-amplitude, 10to 20-μV monophasic (negative) potential of very brief (0.5 to 1 ms) duration. These represent single or synchronized miniature end plate potentials (MEPPs) because of the small number of ACh quanta that are being released all the time. They are normally sparse but are most evident when the recording needle electrode is placed near a motor endplate (“endplate noise”). Fortuitous placement of the needle electrode very close to or in contact with the endplate gives rise to a second type of normal spontaneous activity that is characterized by irregularly discharging high-frequency (50to 100-Hz) biphasic spike discharges, 100 to 300 μV in amplitude (i.e., large enough to cause an isolated