BRIEF REVIEW
Evoked Potential Studes in Neurologcd Diagnosis and Management Michael J. Aminoff, MD, FRCP
Evoked potential studies are an important means of investigating the function of the nervous system in different contexts for research purposes, and can provide fresh insight to the extent of pathological involvement in many neurological disorders. In amyotrophic lateral sclerosis, for example, abnormalities in somatosensory evoked potentials (SEPs) 11, 21 provide evidence of sensory involvement, and in Wilson’s disease multimodality evoked potential studies may show evidence of subclinical dysfunction in each of the major sensory pathways {3]. Evoked potential studies have also come to be used widely for clinical purposes during the last two decades, and a reappraisal of their practical utility as a means of investigating patients with neurological disorders is appropriate now for two reasons. First, remarkable advances in neuroradiology permit the central iiervous system (CNS) to be imaged very effectively by simple noninvasive means. Second, the escalating cost of medical care requires that every aspect of clinical practice be scrutinized in an effort to determine its necessity, and to evaluate the benefits provided with respect to the cost incurred. The clinical utility of evoked potential studies can be considered under several different headings. Sensory Evoked Potentials Detection and Localization of Central Lesions Patients are frequently referred to the Clinical Neurophysiology Laboratory because of suspected mzlltiple sclerosis. In this context, electrophysiological studies are usually requested in order to detect subclinical lesions in the CNS, so that the presence of multiple lesions can be recognized when only a single lesion is evident clinically. When this is the case, the evoked potential studies to be undertaken are those permitting evaluation of CNS regions that are clinically unaffected. For example, in a patient with a cervical myelopathy, the presence of a visual evoked potential (VEP) abnormality is helpful in demonstrating that more than one lesion is present, whereas an SEP abnormality may simply reflect the myelopathy and is therefore of little further help to the clinician. How-
ever, the presence of multifocal disease of the CNS is not in itself diagnostic of multiple sclerosis, and the clinical and electrophysiological findings must therefore be interpreted in the context of the individual case. Thus, patients with certain spinocerebellar degenerations, familial spastic paraplegia, and vitamin E or BI2 deficiency may also have a myelopathy and an accompanying abnormality of the VEP. In this context, the nature of the VEP abnormality may suggest the underlying pathology. In patients with hereditary disorders, for example, the VEP abnormality is usually bilateral and relatively symmetrical, whereas in multiple sclerosis it is commonly markedly asymmetrical. In other instances, patients with suspected multiple sclerosis and ill-defined complaints are investigated by studying the functional integrity of precisely those afferent pathways where a lesion is suspected clinically. Thus, in patients with an uncertain history of blurred vision, the presence of a VEP abnormality is helpful in indicating involvement of the anterior visual pathway. In our experience, electrophysiological techniques are as sensitive as magnetic resonance imaging (MRI) in detecting lesions in patients with definite multiple sclerosis, but less sensitive when multiple sclerosis is only a diagnostic possibility [4]. However, this does not detract from the utility of evoked potential studies in patients in this latter diagnostic category, for several reasons, First, evoked potential studies are usually considerably cheaper than MRI, particularly if the referring physician is discriminating with regard to which modalities are to be tested. Second, the abnormalities on MRI are themselves nonspecific, and are sometimes encountered in normal subjects. By contrast, the rate of false-positive evoked potential abnormalities is negligible when criteria for abnormality are set using appropriate levels of departure from mean values in control subjects. Third, electrophysiological techniques may reveal abnormalities missed by MRI, and vice versa 14-61. Normal electrophysiological findings do not exclude the diagnosis of multiple sclerosis. The role of serial evoked potential studies in following the course of multiple sclerosis by detecting new
From the School of Medicine, University of California, san Francisco, CA.
Address correspondence to Dr Aminoff, Box 0114, Room 794-M, University of California, San Francisco, CA 94143-0114.
Received Feb 21, 1990, and in revised form Apr 27. Accepted for publication May 14, 1990.
706 Copyright 0 1990 by the American Neurological Association
lesions or changes in established ones is less clear. We have found that evoked potentials may sometimes change without any accompanying clinical disturbance of the corresponding region of the CNS, and vice versa, and that there may be excessive variability between test sessions of the responses to stimulation of clinically involved pathways, even when the clinical deficit is stable 171. Furthermore, any change in an already abnormal evoked potential may be of little localizing value or significance, as has been stressed by others [S-lo]. Evoked potential studies may be abnormal in many other disordprs affecting the CNS. For example, the VEP may be abnormal in patients with compressive lesions of the anterior visual pathway such as a sphcnoidal wing meningioma, SEPs are often abnormal with lesions of all sorts involving the medial lemniscus, and brainstem auditory evoked potentials (BAEPs) are commonly abnormal in patients with acoustic neuromas. Thus, their diagnostic value depends on the circumstance in which they are obtained. For example, in a patient in whom an acoustic neuroma is a clinical possibility, abnormal BAEP findings are very helpful in supporting the diagnosis, and normal responses render the diagnosis unlikely. Attempts have sometimes been made to use the evoked potential findings to localize lesions within the CNS. Although this is not inappropriate in principle, precise locahzation by this means may not be possible. This is because the generators of many of the components recorded in evoked potential studies in humans are not known with confidence, and some components have multiple generators. The notion that the various components are generated by the sequential activation of specific anatomical structures along the sensory pathway being tested is intuitively appealing but poorly substantiated. SEPs have been used to evaluate peripheral somatosensory pathways. When elicited by nerve trunk stimulation, the findings are generally unhelpful in patients with isolated radiculopathies. With plexus lesions they may provide misleading information when multiple lesions are present, because the findings will reflect the most distal lesion that is present. Nevertheless, SEPs may be useful in evaluating conduction along inaccessible proximal segments of peripheral nerves or when peripheral sensory nerve action potentials are unobtainable [111.
Evoked Potentials aJ a Prognostic Guide Evoked potential studies may provide a guide to prognosis in patients who have had head injuries or who are in coma for other reasons. As such, they are helpful in supplementing the prognostic information that can be obtained by clinical examination. In anoxicischemic coma, for example, patients with bilateral ab-
sence of cortically generated components of the SEP generally fail to recover cognition, whereas the prognosis is more varied when cortical responses are present on one or both sides 112). The findings may be particularly helpful in the evaluation of patients with suspected brain death when an ancillary diagnostic aid is required for clinical or medicolegal purposes. In this regard, SEP studies are probably more valuable than recording BAEPs, since with the latter all components of the response are often lost in brain-dead patients, in which case some doubt must exist as to whether technical factors or deafness are responsible 1131. In patients with spinal injuries, it may be difficult clinically to determine during the acute phase whether the cord lesion is complete or incomplete. However, the presence (or early return) of SEPs recorded over the scalp following stimulation of a nerve below the level of the lesion indicates that the lesion is incomplete and therefore points to a better prognosis than otherwise {14J
Prediction and Prevention of Neurological Damage by Evoked Potential Monitoring Evoked potentials may be used to monitor the function of neural structures during times of risk, such as during surgical procedures, in order to minimize the risk of damage by permitting the early recognition of any deficit. When such a deficit is due to the surgical procedure, alteration of the procedure may prevent the damage from becoming irreversible. Although widely used for this purpose, the utility of SEP monitoring of cord function during scoliosis surgery is unclear 115, 161. There is no doubt that a change in the intraoperatively recorded SEP may permit the identification of some patients with a high risk of developing a significant neurological deficit postoperatively; in one recent study, 3 (43%) of 7 patients with a marked change in intraoperative SEP findings developed a neurological deficit 1171. Nevertheless, even if an adverse outcome can be correctly predicted, it may not be possible to prevent or ameliorate it despite intraoperative SEP monitoring. Thus, in only 1 patient in the series of Dinner and colleagues [17} was the surgical procedure altered because of a change in the SEP, and the patient still had a postoperative deficit. However, there is an encouraging recent report of 3 patients (of 3 5 1) undergoing orthopedic corrective procedures on the spine in whom an SEP change led to further surgical intervention or a modification of technique, with recovery of the SEP and the absence of any clinical deficit postoperatively [lb]. It is likely (but not certain) that some or all of these patients would have developed major neurological complications had the SEP changes not alerted the surgeon that a problem was developing. It must be stressed that the absence of SEP change does not exclude development of a deficit.
Brief Review: Aminoff: Evoked Potentials in Diagnosis and Management 707
During surgery in the posterior fossa, BAEP recording is helpful in monitoring the functional status of the eighth cranial nerve and of certain brainstem regions, and other electrophysiological techniques are also useful in this regard. There is some evidence to suggest that the recording of SEPs by stimulation of a nerve in the legs may help to detect which patients, in whom cervical spondylosis but no clinical evidence of cord involvement is present, are likely to develop a myelopathy, so that surgical treatment can be considered at a relatively early stage 118). However, this use of SEPs remains to be established more definitively.
Detemination of End Organ Fzlnction Evoked potential studies have been used effectively to provide a measure of auditory or visual function in patients unable to cooperate for behavioral testing. Thus, newborn infants with a high risk of hearing loss (e.g., because of family history, congenital or neonatal infections, severe asphyxia, hyperbilirubinemia, or prematurity) can be evaluated by BAEP studies to determine the threshold of the electrophysiological response. Based on their own experience and that of others with this technique, Picton and associates reported that between 1 and 5% of graduates of a neonatal intensive care unit will have bilateral hearing loss requiring early provision of hearing aids to prevent developmental delay {19]. The VEP has similarly been used to measure visual acuity, validate retinoscopic findings, and detect and monitor amblyopia in infants and children, for example by comparing the response elicited by stimulation of each eye with small checks (if monocular amblyopia is suspected), or by plotting the relationship of VEP amplitude to check size when the VEP is elicited by checks of different size {20). Evaluation of Nonorganic Symptoms Evoked potential studies are sometimes helpful in evaluating symptoms suspected to be nonorganic in origin. Their main role in this context is in detecting an abnormality in the sensory system in question, thereby suggesting that symptoms are not hysterical in nature but relate to CNS dysfunction. The converse, however, is not necessarily true. Completely normal evoked potentials cannot be taken in themselves to imply a nonorganic basis of symptoms and the absence of pathological involvement of the afferent pathway under study, although this finding would be one more factor to take into account when considering such a possibility. In patients with possibly factitious blindness or visual impairment, interpretation of the VEP findings is more complex because the findings may be normal with cortical blindness due to lesions of area 17. or of areas 18 and 19 {21-23f. 708
Annals of Neurology Vol 28 No 5
Motor Evoked Potentials Noninvasive transcranial magnetic or electrical stimulation of the brain has recently aroused interest as a means of exploring cerebral function. Stimulation by a magnetic field (generated by a brief electrical current passing through a coil of wire) is perhaps the superior approach for cerebral stimulation because it causes little discomfort. It appears to pose no immediate safety hazards, but the long-term effects of repeated magnetic (or electrical) stimulation are unknown. Both magnetic and electrical stimulation of the brain can elicit motor responses. The recording of these socalled motor evoked potentials elicited by cerebral and by spinal or paraspinal (i.e., proximal nerve root) stimulation has permitted measurement of response latency and estimates of central conduction time in descending motor pathways. Abnormalities have been described in patients with multiple sclerosis [24], motor neuron disease [25], cerebral infarction, cervical myelopathy [26], parkinsonism, and degenerative ataxias [27). However, the clinical utility of such motor studies is unclear and-in the United States-ethical considerations and governmental regulations have limited the use of magnetic stimulation of the CNS to investigational contexts requiring approval by the Food and Drug Administration. The introduction into routine clinical practice of motor evoked potential studies will depend on technical and methodological refinements and standardization, and will require further determination of the extent to which responses vary in normal subjects with physical factors (such as height) and physiological processes (such as ageing, ongoing volitional activity, and mental state). It will then be necessary to determine whether the recording of motor evoked potentials can facilitate neurological diagnosis or can otherwise improve patient management. Preliminary studies suggest, however, that motor evoked potentials may be useful in detecting subclinical dysfunction in patients with suspected multiple sclerosis or early spondylotic myelopathy, even when SEPs are normal 124, 261, in providing a guide to prognosis for motor recovery after cerebral infarction or spinal cord injury [26], and in permitting the monitoring of motor pathways during spinal surgery [28]. General Comment on the Use of Evoked Potential Studies in Clinical Practice Imaging studies provide information about the anatomy of the CNS and the presence of any structural abnormalities, but not about neurological function. By contrast, the history, neurological examination, and electrophysiological studies provide information concerning the functional integrity of the nervous system. In some instances, anatomical abnormalities may not cause any neurological dysfunction, and in other circumstances it may not be possible to detect by imaging
November 1990
techniques an anatomical basis for a disturbance of cerebral or spinal function. Thus, electrophysiological and radiological techniques are complementary rather than alternatives. They provide different types of information that need to be integrated with the context in which they are obtained in order to define fully the clinical status of individual patients. It may ultimately be necessary to review the costeffectiveness of the many different investigative techniques that are currently available to neurologists because their use can be influenced by changes in the resources available to pay for them. Unfortunately, few studies concerning the cost-effectiveness of different technologies have been undertaken and there is little information available concerning charges billed for these different procedures. In this regard, personal communication (with Dr W. Aubry, Medical Director) reveals that over a 12-month period ending January 31, 1990, Blue Shield of California, which serves a base of approximately 1.65 million non-Medicare members and their dependents, was billed $11.2 million for comprehensive medical consultations of all sorts. The proportion of neurological consultations cannot be determined reliably. Over this same time there were billings (not all of which were requested by neurologists) of $5.1 million for professional services in interpreting MRI brain studies, $1.7 million for computed tomographic (CT) scans of the head, and $0.5 million for evoked potential studies (all sensory modalities combined). No data are available to determine the appropriateness of these various studies and the extent to which they influenced clinical management. The utilization of evoked potential studies seems to vary widely among neurologists and their value depends on the manner in which they are used. The sensible utilization of a particular technique depends on awareness of its scope and limitations by referring physicians, and the indiscriminate referral of patients for study is clearly inappropriate. Furthermore, the effectiveness of a particular technology in any given context will depend in part on the expertise of the person employing that technology. In the case of evoked potential studies as currently performed, recording techniques have not been standardized (despite efforts of the American Electroencephalographic Society to do so) and recordings are interpreted by persons who differ widely in their background, training, and experience. Some persons reporting evoked potential studies have had no medical training, others have had no formal training in clinical neurophysiology, and many fail to appreciate or indicate the clinical relevance of the electrophysiological findings. Further, evoked potential studies are often performed by the very physician who requested them, which is unfortunate if only because the motives for undertaking the studies may be questioned when the studies seem to have little influence on patient management.
The incidence of false-positive and false-negative results depends in part on the experience of the technical and reporting staff, so that criteria for abnormality should be defined quantitatively, based on control data obtained by each laboratory in normal subjects. In addition to providing material with which to compare the findings obtained in patients, this also allows the technical and reporting staff to gain experience before studying patients. In particular, it provides an opportunity to appreciate the wide variability in morphology, amplitude, and latency of evoked potentials in normal subjects, and the variety of nonpathological factors that can influence the electrophysiological findings. Evoked potential findings are not pathognomonic of specific diseases, any more than is an extensor plantar response. The electrophysiological findings are of diagnostic value simply in reflecting the extent of neurological impairment, indicating the presence, broad distribution, and functional relevance of lesions in the CNS. As such, evoked potential studies are best regarded as an extension of the clinical examination, but with the added advantage of providing objective, reproducible, and quantitative data. Such data permit comparisons to be made over time in the same individual. The evoked potential findings may reveal the presence of subclinical lesions of the CNS, and may indicate the organic nature and probable basis of symptoms that are relatively nonspecific in nature. For example, the nature of a vague complaint of “dizziness” may be clarified if BAEP studies are abnormal. Depending on the clinical circumstances, differential diagnosis, and reason for referral to the Clinical Neurophysiology Laboratory, normal evoked potential findings may be as helpful as abnormal findings, and their value should not be discounted. The utility of evoked potential studies in a number of neurological conditions is still uncertain. Although abnormal findings have been reported in patients with a variety of disorders, they are often more of academic interest than practical relevance. Studies to indicate the clinical value of the technique in many conditions are lacking. The presence of electrophysiological differences between a group of normal subjects and a group of patients with a particular disorder does not necessarily mean that evoked potential studies will be helpful in evaluating individual patients with that disorder. Unless evoked potential studies provide information that is helpful in establishing a diagnosis or prognosis, or in guiding appropriate management or treatment, they are of little value to the patient and the clinical necessity for performing them becomes questionable. Conclusions Evoked potential studies provide important information about the functional integrity of the major afferent systems, and the development and commercial availability of magnetic stimulators suggest that it will
Brief Review: Aminoff: Evoked Potentials in Diagnosis and Management 709
soon be possible to evaluate motor function by analogous means. Such studies are important for clinical as well as for academic purposes in extending understanding of cerebral function, and characterizing the distribution and pathophysiology of disease processes. Their clinical utility is increased if the scope and limitations of the technique are familiar to referring physicians, and the reason for referral of individual patients is indicated so that appropriate studies can be undertaken, standard techniques can be modified as necessary, and the findings interpreted in light of the clinical context. Interpretation of the findings requires an appreciation of the wide range of normal findings and of the many nonpathological variables affecting the electrophysiological findings. Additional training (and certification) in clinical neurophysiology after completion of a neurology residency program is therefore advantageous for those intending to undertake evoked potential studies. Although evoked potential abnormalities have been reported in different neurological disorders, the practical relevance of these findings in the management of individual cases is often obscure and needs clarification by more focused studies. Nevertheless, evoked potential studies are of value in detecting functional disturbances in the CNS and in suggesting the nature or basis of vague nonspecific complaints. They are also valuable in providing a guide to prognosis in certain circumstances, investigating brain-death suspects, monitoring the function of certain neural structures so as to preserve their integrity, and evaluating ocular and auditory function when behavioral testing is precluded because of age and inability to cooperate.
References 1. Bosch EP, Yamada T, Kimura J. Somatosensory evoked potentials in motor neuron disease. Muscle Nerve 1985;8:556-562 2. Radtke RA, Erwin A, Erwin CW. Abnormal sensory evoked potentials in amyotrophic lateral sclerosis. Neurology 1986;36: 796-801 3. Chu N-S. Sensory evoked potentials in Wilson’s disease. Brain 1986;109:491-507 4. Cutler JR, Aminoff MJ, Brant-Zawadzki M. Evaluation of patients with multiple sclerosis by evoked potentials and magnetic resonance imaging: a comparative study. Ann Neurol 1986;ZO: 645-648 5 . l r s h n e r HS, Tsai SI, Runge VM, Price AC. Magnetic resonance imaging and other techniques in the diagnosis of multiple sclerosis. Arch Neurol 1985;42:859-863 6. Giesser BS, Kurtzberg D, Vaughan H G Jr, et al. Trimodal evoked potentials compared with magnetic resonance imaging in the diagnosis of multiple sclerosis. Arch Neurol 1987;44: 281-284 7. Aminoff MJ, Davis SL, Panitch HS. Serial evoked potential studies in patients with definite multiple sclerosis: clinical relevance, Arch Neurol 1984;41:1197-1202 8. Likosky W, Elmore RS. Exacerbation detection in multiple sclerosis by clinical and evoked potential techniques: a preliminary report. In: Courjon J, Mauguiere F, Revol M, eds. Clinical ap-
710 Annals of Neurology
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plications of evoked potentials in neurology. New York Raven Press, 1982:535-540 9 Robinson K, Rudge P. The stabhty of the auditory evoked potentials in normal man and patients with multiple sclerosis. J Neurol Sci 1978;36:147-156 10 Confavreux C, Mauguiere F, Courjon J, et al. Course of visual evoked potentials in multiple sclerosis: electroclinical correlations and pathophysiological considerations in 2 5 patients. In: Courjon J, Mauguiere F, Revol M, eds. Clinical applications of evoked potentials in neurology. New York: Raven Press, 1982:541-550 11 Aminoff MJ. Use of somatoscnsory evoked potentials to evaluate the peripheral nervous system. J Clin Neurophysiol 1987; 4:135-144 12 Brunko E, Zegers de Bey1 L). Prognostic value of early cortical somatosensory evoked potentials after resuscitation from cardiac arrest. Electroencephalogr Clin Neurophysiol 1987;66:1524 13 Goldie WD, Chiappa KH, Young RR,Brooks EB. Brainstem auditory and short-latency somatosensory evoked responses in brain death. Neurology 1981;31:248-256 14 Rowed DW, McLean JAG, Tator CH. Somatosensory evoked potentials in acute spinal cord injury: prognostic value. Surg N e w 1 1978;9:203-210 15 Aminoff MJ. Intraoperative monitoring by evoked potentials for spinal cord surgery: the cons. Electroencephalogr Clin Neurophysiol 1989;73:378-380 16 Daube JR. Intraoperative monitoring by evoked potentials for spinal cord surgery: the pros. Electroencephalogr Clin Neurophysiol 1989;73:374-377 17 Dinner DS, Luders H, Lesser RP, et al. Intraoperative spinal somatosensory evoked potential monitoring. J Neurosurg 1986; 65:807-814 18. Y u YL, Jones SJ. Somatosensory evoked potentials in cervical spondylosis. Correlation of median, ulnar and posterior tibial nerve responses with clinical and radiological findings. Brain 1985;108:273-300 19. Picton TW, Taylor MJ, Durieux-Smith A, Edwards CG. Brainstem auditory evoked potentials in pediatrics. In: Aminoff MJ, ed. Electrodiagnosis in clinical neurology. 2nd ed. New York: Churchill Lvingstone, 1986:505-534 20. Sokol S. Pattern visual evoked potentials: their use in pehatric ophthalmology. Int Ophthalmol Clin 1980;20:251-268 21. Bodis-Wollner I, Atkin A, Raab E, Wolkstein M. Visual association cortex and vision in man: pattern-evoked occipital potentials in a blind boy. Science 1977;198:629-631 22. Celesia GG, Archer CR, Kuroiwa Y, Goldfader PR. Visual function of the extrageniculo-calcarinesystem in man. Relationship to cortical blindness. Arch Neurol 1980;37:704-706 23. Frank Y, Torres F. Visual evoked potentials in the evaluation of “cortical blindness” in children. Ann Neurol 1979;6:126129 24. Hess CW, Mills KR, Murray NMF, Schriefer TN. Magnetic brain stimulation: central motor conduction studies in multiple sclerosis. Ann Neurol 1987;22:744-752 25. Hugon J, Lubeau M, Tabaraud F, et al. Central motor conduction in motor neuron disease. Ann Neurol 1987;22:544-546 26. Thompson PD, Dick JPR, Asselman P, et al. Examination of motor function in lesions of the spinal cord by stimulation of the motor cortex. Ann Neurol 1987;21:389-396 27. Claus D, Harding AE, Hess CW, et al. Central motor conduction in degenerative ataxic disorders: a magnetic stimulation study. J Neurol Neurosurg Psychiatry 1988;51:790-795 28. Boyd SG, Rothwell JC, Cowan JMA, et al. A method of monitoring function in corticospinal pathways during scoliosis surgery with a note on motor conduction velocities. J Neurol Neurosurg Psychlatry 1986;49:25 1-2 57
N o v e m b e r 1990
Evoked Potential Studes in Neurologcd Diagnosis and Management Michael J. Aminoff, MD, FRCP
Evoked potential studies are an important means of investigating the function of the nervous system in different contexts for research purposes, and can provide fresh insight to the extent of pathological involvement in many neurological disorders. In amyotrophic lateral sclerosis, for example, abnormalities in somatosensory evoked potentials (SEPs) 11, 21 provide evidence of sensory involvement, and in Wilson’s disease multimodality evoked potential studies may show evidence of subclinical dysfunction in each of the major sensory pathways {3]. Evoked potential studies have also come to be used widely for clinical purposes during the last two decades, and a reappraisal of their practical utility as a means of investigating patients with neurological disorders is appropriate now for two reasons. First, remarkable advances in neuroradiology permit the central iiervous system (CNS) to be imaged very effectively by simple noninvasive means. Second, the escalating cost of medical care requires that every aspect of clinical practice be scrutinized in an effort to determine its necessity, and to evaluate the benefits provided with respect to the cost incurred. The clinical utility of evoked potential studies can be considered under several different headings. Sensory Evoked Potentials Detection and Localization of Central Lesions Patients are frequently referred to the Clinical Neurophysiology Laboratory because of suspected mzlltiple sclerosis. In this context, electrophysiological studies are usually requested in order to detect subclinical lesions in the CNS, so that the presence of multiple lesions can be recognized when only a single lesion is evident clinically. When this is the case, the evoked potential studies to be undertaken are those permitting evaluation of CNS regions that are clinically unaffected. For example, in a patient with a cervical myelopathy, the presence of a visual evoked potential (VEP) abnormality is helpful in demonstrating that more than one lesion is present, whereas an SEP abnormality may simply reflect the myelopathy and is therefore of little further help to the clinician. How-
ever, the presence of multifocal disease of the CNS is not in itself diagnostic of multiple sclerosis, and the clinical and electrophysiological findings must therefore be interpreted in the context of the individual case. Thus, patients with certain spinocerebellar degenerations, familial spastic paraplegia, and vitamin E or BI2 deficiency may also have a myelopathy and an accompanying abnormality of the VEP. In this context, the nature of the VEP abnormality may suggest the underlying pathology. In patients with hereditary disorders, for example, the VEP abnormality is usually bilateral and relatively symmetrical, whereas in multiple sclerosis it is commonly markedly asymmetrical. In other instances, patients with suspected multiple sclerosis and ill-defined complaints are investigated by studying the functional integrity of precisely those afferent pathways where a lesion is suspected clinically. Thus, in patients with an uncertain history of blurred vision, the presence of a VEP abnormality is helpful in indicating involvement of the anterior visual pathway. In our experience, electrophysiological techniques are as sensitive as magnetic resonance imaging (MRI) in detecting lesions in patients with definite multiple sclerosis, but less sensitive when multiple sclerosis is only a diagnostic possibility [4]. However, this does not detract from the utility of evoked potential studies in patients in this latter diagnostic category, for several reasons, First, evoked potential studies are usually considerably cheaper than MRI, particularly if the referring physician is discriminating with regard to which modalities are to be tested. Second, the abnormalities on MRI are themselves nonspecific, and are sometimes encountered in normal subjects. By contrast, the rate of false-positive evoked potential abnormalities is negligible when criteria for abnormality are set using appropriate levels of departure from mean values in control subjects. Third, electrophysiological techniques may reveal abnormalities missed by MRI, and vice versa 14-61. Normal electrophysiological findings do not exclude the diagnosis of multiple sclerosis. The role of serial evoked potential studies in following the course of multiple sclerosis by detecting new
From the School of Medicine, University of California, san Francisco, CA.
Address correspondence to Dr Aminoff, Box 0114, Room 794-M, University of California, San Francisco, CA 94143-0114.
Received Feb 21, 1990, and in revised form Apr 27. Accepted for publication May 14, 1990.
706 Copyright 0 1990 by the American Neurological Association
lesions or changes in established ones is less clear. We have found that evoked potentials may sometimes change without any accompanying clinical disturbance of the corresponding region of the CNS, and vice versa, and that there may be excessive variability between test sessions of the responses to stimulation of clinically involved pathways, even when the clinical deficit is stable 171. Furthermore, any change in an already abnormal evoked potential may be of little localizing value or significance, as has been stressed by others [S-lo]. Evoked potential studies may be abnormal in many other disordprs affecting the CNS. For example, the VEP may be abnormal in patients with compressive lesions of the anterior visual pathway such as a sphcnoidal wing meningioma, SEPs are often abnormal with lesions of all sorts involving the medial lemniscus, and brainstem auditory evoked potentials (BAEPs) are commonly abnormal in patients with acoustic neuromas. Thus, their diagnostic value depends on the circumstance in which they are obtained. For example, in a patient in whom an acoustic neuroma is a clinical possibility, abnormal BAEP findings are very helpful in supporting the diagnosis, and normal responses render the diagnosis unlikely. Attempts have sometimes been made to use the evoked potential findings to localize lesions within the CNS. Although this is not inappropriate in principle, precise locahzation by this means may not be possible. This is because the generators of many of the components recorded in evoked potential studies in humans are not known with confidence, and some components have multiple generators. The notion that the various components are generated by the sequential activation of specific anatomical structures along the sensory pathway being tested is intuitively appealing but poorly substantiated. SEPs have been used to evaluate peripheral somatosensory pathways. When elicited by nerve trunk stimulation, the findings are generally unhelpful in patients with isolated radiculopathies. With plexus lesions they may provide misleading information when multiple lesions are present, because the findings will reflect the most distal lesion that is present. Nevertheless, SEPs may be useful in evaluating conduction along inaccessible proximal segments of peripheral nerves or when peripheral sensory nerve action potentials are unobtainable [111.
Evoked Potentials aJ a Prognostic Guide Evoked potential studies may provide a guide to prognosis in patients who have had head injuries or who are in coma for other reasons. As such, they are helpful in supplementing the prognostic information that can be obtained by clinical examination. In anoxicischemic coma, for example, patients with bilateral ab-
sence of cortically generated components of the SEP generally fail to recover cognition, whereas the prognosis is more varied when cortical responses are present on one or both sides 112). The findings may be particularly helpful in the evaluation of patients with suspected brain death when an ancillary diagnostic aid is required for clinical or medicolegal purposes. In this regard, SEP studies are probably more valuable than recording BAEPs, since with the latter all components of the response are often lost in brain-dead patients, in which case some doubt must exist as to whether technical factors or deafness are responsible 1131. In patients with spinal injuries, it may be difficult clinically to determine during the acute phase whether the cord lesion is complete or incomplete. However, the presence (or early return) of SEPs recorded over the scalp following stimulation of a nerve below the level of the lesion indicates that the lesion is incomplete and therefore points to a better prognosis than otherwise {14J
Prediction and Prevention of Neurological Damage by Evoked Potential Monitoring Evoked potentials may be used to monitor the function of neural structures during times of risk, such as during surgical procedures, in order to minimize the risk of damage by permitting the early recognition of any deficit. When such a deficit is due to the surgical procedure, alteration of the procedure may prevent the damage from becoming irreversible. Although widely used for this purpose, the utility of SEP monitoring of cord function during scoliosis surgery is unclear 115, 161. There is no doubt that a change in the intraoperatively recorded SEP may permit the identification of some patients with a high risk of developing a significant neurological deficit postoperatively; in one recent study, 3 (43%) of 7 patients with a marked change in intraoperative SEP findings developed a neurological deficit 1171. Nevertheless, even if an adverse outcome can be correctly predicted, it may not be possible to prevent or ameliorate it despite intraoperative SEP monitoring. Thus, in only 1 patient in the series of Dinner and colleagues [17} was the surgical procedure altered because of a change in the SEP, and the patient still had a postoperative deficit. However, there is an encouraging recent report of 3 patients (of 3 5 1) undergoing orthopedic corrective procedures on the spine in whom an SEP change led to further surgical intervention or a modification of technique, with recovery of the SEP and the absence of any clinical deficit postoperatively [lb]. It is likely (but not certain) that some or all of these patients would have developed major neurological complications had the SEP changes not alerted the surgeon that a problem was developing. It must be stressed that the absence of SEP change does not exclude development of a deficit.
Brief Review: Aminoff: Evoked Potentials in Diagnosis and Management 707
During surgery in the posterior fossa, BAEP recording is helpful in monitoring the functional status of the eighth cranial nerve and of certain brainstem regions, and other electrophysiological techniques are also useful in this regard. There is some evidence to suggest that the recording of SEPs by stimulation of a nerve in the legs may help to detect which patients, in whom cervical spondylosis but no clinical evidence of cord involvement is present, are likely to develop a myelopathy, so that surgical treatment can be considered at a relatively early stage 118). However, this use of SEPs remains to be established more definitively.
Detemination of End Organ Fzlnction Evoked potential studies have been used effectively to provide a measure of auditory or visual function in patients unable to cooperate for behavioral testing. Thus, newborn infants with a high risk of hearing loss (e.g., because of family history, congenital or neonatal infections, severe asphyxia, hyperbilirubinemia, or prematurity) can be evaluated by BAEP studies to determine the threshold of the electrophysiological response. Based on their own experience and that of others with this technique, Picton and associates reported that between 1 and 5% of graduates of a neonatal intensive care unit will have bilateral hearing loss requiring early provision of hearing aids to prevent developmental delay {19]. The VEP has similarly been used to measure visual acuity, validate retinoscopic findings, and detect and monitor amblyopia in infants and children, for example by comparing the response elicited by stimulation of each eye with small checks (if monocular amblyopia is suspected), or by plotting the relationship of VEP amplitude to check size when the VEP is elicited by checks of different size {20). Evaluation of Nonorganic Symptoms Evoked potential studies are sometimes helpful in evaluating symptoms suspected to be nonorganic in origin. Their main role in this context is in detecting an abnormality in the sensory system in question, thereby suggesting that symptoms are not hysterical in nature but relate to CNS dysfunction. The converse, however, is not necessarily true. Completely normal evoked potentials cannot be taken in themselves to imply a nonorganic basis of symptoms and the absence of pathological involvement of the afferent pathway under study, although this finding would be one more factor to take into account when considering such a possibility. In patients with possibly factitious blindness or visual impairment, interpretation of the VEP findings is more complex because the findings may be normal with cortical blindness due to lesions of area 17. or of areas 18 and 19 {21-23f. 708
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Motor Evoked Potentials Noninvasive transcranial magnetic or electrical stimulation of the brain has recently aroused interest as a means of exploring cerebral function. Stimulation by a magnetic field (generated by a brief electrical current passing through a coil of wire) is perhaps the superior approach for cerebral stimulation because it causes little discomfort. It appears to pose no immediate safety hazards, but the long-term effects of repeated magnetic (or electrical) stimulation are unknown. Both magnetic and electrical stimulation of the brain can elicit motor responses. The recording of these socalled motor evoked potentials elicited by cerebral and by spinal or paraspinal (i.e., proximal nerve root) stimulation has permitted measurement of response latency and estimates of central conduction time in descending motor pathways. Abnormalities have been described in patients with multiple sclerosis [24], motor neuron disease [25], cerebral infarction, cervical myelopathy [26], parkinsonism, and degenerative ataxias [27). However, the clinical utility of such motor studies is unclear and-in the United States-ethical considerations and governmental regulations have limited the use of magnetic stimulation of the CNS to investigational contexts requiring approval by the Food and Drug Administration. The introduction into routine clinical practice of motor evoked potential studies will depend on technical and methodological refinements and standardization, and will require further determination of the extent to which responses vary in normal subjects with physical factors (such as height) and physiological processes (such as ageing, ongoing volitional activity, and mental state). It will then be necessary to determine whether the recording of motor evoked potentials can facilitate neurological diagnosis or can otherwise improve patient management. Preliminary studies suggest, however, that motor evoked potentials may be useful in detecting subclinical dysfunction in patients with suspected multiple sclerosis or early spondylotic myelopathy, even when SEPs are normal 124, 261, in providing a guide to prognosis for motor recovery after cerebral infarction or spinal cord injury [26], and in permitting the monitoring of motor pathways during spinal surgery [28]. General Comment on the Use of Evoked Potential Studies in Clinical Practice Imaging studies provide information about the anatomy of the CNS and the presence of any structural abnormalities, but not about neurological function. By contrast, the history, neurological examination, and electrophysiological studies provide information concerning the functional integrity of the nervous system. In some instances, anatomical abnormalities may not cause any neurological dysfunction, and in other circumstances it may not be possible to detect by imaging
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techniques an anatomical basis for a disturbance of cerebral or spinal function. Thus, electrophysiological and radiological techniques are complementary rather than alternatives. They provide different types of information that need to be integrated with the context in which they are obtained in order to define fully the clinical status of individual patients. It may ultimately be necessary to review the costeffectiveness of the many different investigative techniques that are currently available to neurologists because their use can be influenced by changes in the resources available to pay for them. Unfortunately, few studies concerning the cost-effectiveness of different technologies have been undertaken and there is little information available concerning charges billed for these different procedures. In this regard, personal communication (with Dr W. Aubry, Medical Director) reveals that over a 12-month period ending January 31, 1990, Blue Shield of California, which serves a base of approximately 1.65 million non-Medicare members and their dependents, was billed $11.2 million for comprehensive medical consultations of all sorts. The proportion of neurological consultations cannot be determined reliably. Over this same time there were billings (not all of which were requested by neurologists) of $5.1 million for professional services in interpreting MRI brain studies, $1.7 million for computed tomographic (CT) scans of the head, and $0.5 million for evoked potential studies (all sensory modalities combined). No data are available to determine the appropriateness of these various studies and the extent to which they influenced clinical management. The utilization of evoked potential studies seems to vary widely among neurologists and their value depends on the manner in which they are used. The sensible utilization of a particular technique depends on awareness of its scope and limitations by referring physicians, and the indiscriminate referral of patients for study is clearly inappropriate. Furthermore, the effectiveness of a particular technology in any given context will depend in part on the expertise of the person employing that technology. In the case of evoked potential studies as currently performed, recording techniques have not been standardized (despite efforts of the American Electroencephalographic Society to do so) and recordings are interpreted by persons who differ widely in their background, training, and experience. Some persons reporting evoked potential studies have had no medical training, others have had no formal training in clinical neurophysiology, and many fail to appreciate or indicate the clinical relevance of the electrophysiological findings. Further, evoked potential studies are often performed by the very physician who requested them, which is unfortunate if only because the motives for undertaking the studies may be questioned when the studies seem to have little influence on patient management.
The incidence of false-positive and false-negative results depends in part on the experience of the technical and reporting staff, so that criteria for abnormality should be defined quantitatively, based on control data obtained by each laboratory in normal subjects. In addition to providing material with which to compare the findings obtained in patients, this also allows the technical and reporting staff to gain experience before studying patients. In particular, it provides an opportunity to appreciate the wide variability in morphology, amplitude, and latency of evoked potentials in normal subjects, and the variety of nonpathological factors that can influence the electrophysiological findings. Evoked potential findings are not pathognomonic of specific diseases, any more than is an extensor plantar response. The electrophysiological findings are of diagnostic value simply in reflecting the extent of neurological impairment, indicating the presence, broad distribution, and functional relevance of lesions in the CNS. As such, evoked potential studies are best regarded as an extension of the clinical examination, but with the added advantage of providing objective, reproducible, and quantitative data. Such data permit comparisons to be made over time in the same individual. The evoked potential findings may reveal the presence of subclinical lesions of the CNS, and may indicate the organic nature and probable basis of symptoms that are relatively nonspecific in nature. For example, the nature of a vague complaint of “dizziness” may be clarified if BAEP studies are abnormal. Depending on the clinical circumstances, differential diagnosis, and reason for referral to the Clinical Neurophysiology Laboratory, normal evoked potential findings may be as helpful as abnormal findings, and their value should not be discounted. The utility of evoked potential studies in a number of neurological conditions is still uncertain. Although abnormal findings have been reported in patients with a variety of disorders, they are often more of academic interest than practical relevance. Studies to indicate the clinical value of the technique in many conditions are lacking. The presence of electrophysiological differences between a group of normal subjects and a group of patients with a particular disorder does not necessarily mean that evoked potential studies will be helpful in evaluating individual patients with that disorder. Unless evoked potential studies provide information that is helpful in establishing a diagnosis or prognosis, or in guiding appropriate management or treatment, they are of little value to the patient and the clinical necessity for performing them becomes questionable. Conclusions Evoked potential studies provide important information about the functional integrity of the major afferent systems, and the development and commercial availability of magnetic stimulators suggest that it will
Brief Review: Aminoff: Evoked Potentials in Diagnosis and Management 709
soon be possible to evaluate motor function by analogous means. Such studies are important for clinical as well as for academic purposes in extending understanding of cerebral function, and characterizing the distribution and pathophysiology of disease processes. Their clinical utility is increased if the scope and limitations of the technique are familiar to referring physicians, and the reason for referral of individual patients is indicated so that appropriate studies can be undertaken, standard techniques can be modified as necessary, and the findings interpreted in light of the clinical context. Interpretation of the findings requires an appreciation of the wide range of normal findings and of the many nonpathological variables affecting the electrophysiological findings. Additional training (and certification) in clinical neurophysiology after completion of a neurology residency program is therefore advantageous for those intending to undertake evoked potential studies. Although evoked potential abnormalities have been reported in different neurological disorders, the practical relevance of these findings in the management of individual cases is often obscure and needs clarification by more focused studies. Nevertheless, evoked potential studies are of value in detecting functional disturbances in the CNS and in suggesting the nature or basis of vague nonspecific complaints. They are also valuable in providing a guide to prognosis in certain circumstances, investigating brain-death suspects, monitoring the function of certain neural structures so as to preserve their integrity, and evaluating ocular and auditory function when behavioral testing is precluded because of age and inability to cooperate.
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