FLASH EVOKED POTENTIALS IN MIGRAINE Cathy MacLean, B.A. Otto Appenzeller, M.D., Ph.D. J. T. Cordaro, Ph.D. John Rhodes, Ph.D. From the University of New Mexico School of Medicine, Departments of Neurology and Psychology, Albuquerque, New Mexico 87131 A VOLLEY of nerve impulses occurs in response to light falling on the retina. These are transmitted through the optic nerve tract and radiation to the occipital cortex. This electrical response can be recorded through scalp electrodes using appropriate averaging techniques. The latency and wave forms of the potential evoked by bright flashes varies somewhat amongst individuals; nevertheless, in patients having lateralized visual deficits simultaneously recorded interhemispheric differences in the visual evoked responses might be of interest. When patients with headache are examined by conventional electroencephalography the records on the whole do not differ from comparable headache free subjects. However, in patients with vascular headache of the migrainous type there is an increased incidence of abnormal electroencephalograms which fall into two categories.1 In some the records taken during headache free periods show persistent non-focal abnormalities, the genesis of which is not clear but a relationship to epilepsy has been proposed. In the second category, focal abnormalities can be recognized. These can be further subdivided into records which are only temporarily abnormal during a migrainous attack often associated with focal motor or sensory deficits. This is attributed to transient ischemia in the appropriate areas of the brain. Another subdivision is focal electroencephalographic change which occurs during migrainous headaches associated with motor sensory or mental dysfunction and which takes hours or days to disappear. It has been suggested that this type of longer lasting abnormality is related to local edema of the brain. Electroencephalographic changes also occur during headache free intervals in some patients with severe and often persistent motor sensory or intellectual deficits. These rare persistent focal abnormalities have been attributed to cerebral infarction. A frequent source of difficulty in the diagnosis of migraine is the lack of clinical or electroencephalographic deficits. Even during an attack of migraine it is rare to find objective evidence of neurologic dysfunction. Because frequent accompaniments of migraine are visual symptoms we decided to test the integrity of the visual system in patients with vascular headaches of the migrainous type. This study was based on the assumption that migraineurs with a history of a lateralized visual aura might show significant interhemispheric asymmetries in the visual evoked potentials, whereas those with common migraine would not. SUBJECTS AND METHODS Eight migraine patients and five non-migrainous controls were studied. Some clinical findings in patients are summarized in Table I. The control group consisted of four women and one man, ranging in age from 20 to 40 years. These subjects had rare headaches only and no family history of migraine. No permanent neurological abnormalities were found on physical examination of the patients. Transient neurologic deficits occurred sometimes after the visual aura. Vertigo was occasionally associated with headache in four patients with chronic migraine and nausea invariably occurred at some stage of the attack in all. Three patients had sensory deficits contralateral to the pain. In two each hemisphere was
TABLE I Age, Duration of Aura Case Yrs. Sex Migraine (yrs.) Visual Transient Neurologic Deficits EEG I 19 F l1 Yes No Normal 2 23 F l0 Yes Hemisensory Deficit Diffuse slowing 3 24 F 14 Yes Dysphasia; Hemisensory Deficit Normal 4 30 F 15 Yes Dysphasia; Hemisensory Deficit Normal 5 49 F 15 No No Diffuse slowing 6 26 F 1 No No Normal 7 25 F 20 No No Diffuse slowing Slight asymmetry 8 27 M 14 No No Normal involved with equal frequency. The third patient, however, had right sided headaches only. This patient had, simultaneously with the pain, ipsilateral visual deficits. EEG and brain scan in this patient were normal (Case 4). All subjects were medication free for two days prior to the tests. The procedure was explained and they were informed of the artifacts produced by muscle tension, eye movement, and changes in body position. A brief period of adaptation to the experimental situation during which artifacts could be assessed and eliminated preceded the actual tests. APPARATUS AND PRODEDURE Subjects were seated in a darkened room with the head toward the center of a stainless steel hemisphere, the distance from the nasion to a point in the center of the hemisphere being 30cm. The hemisphere was non-reflecting white in color and measured 78cm. in diameter. It was illuminated by a Grass PS2 photo-stimulator (intensity 16) which was positioned above the subject's head. The subject's eyes were closed. In each test session 100 flashes were presented at random intervals of 2 to 5 seconds. The EEG was recorded at standard settings on a Grass Model 78 polygraph with electrodes placed on the scalp. Ipsilateral ear references to parietal and occipital electrodes were used. The EEG was also recorded on a Honeywell 5600 analogue tape deck and continually monitored by a Tektronix Type 502A dual beam oscilloscope. The photic stimulation acted as a marker and triggered a link-8 computer which digitized and averaged the EEG for each 512 msec period after a flash. Each averaged evoked response with its standard deviation was displayed on the oscilloscope of the computer. The tabulation of latency and amplitude of the various components of the waveform was accomplished through the display of the X-Y coordinates corresponding to the position of a moveable cursor. A photograph was taken of each response. These photographs were later presented to two judges not involved in the study. They were asked to identify, from photographs, subjects with interhemispheric differences. All patients except case 1 were tested both during a migraine attack and a headache free interval. Control subjects were tested on one occasion only. RESULTS The typical evoked potentials were sinusoidal multiphasic waves with five components (Fig. 1). The earliest positive deflection (P1) had an onset time of 50 to 75 msec. After this a negative deflection (N1) occurred between 60 and 90 msec. later. A larger positive deflection (P2) was found after 80-100 msec. and a still larger negative component (N2) at 125 to 140 msec. Finally a large enduring positive deflection (P3) occurred between 179 and
200 msec. This component was usually succeeded by an after discharge of 10 to 12 hz. A separation of patients into two groups by two independent observers was achieved (100% correct). The degree of interhemispheric asymmetries distinguished all classic migraineurs tested during the aura. This group was also correctly separated into whether they were during an attack of migraine or headache free. One patient, however, showed marked asymmetries during both attack and headache free period (Case 4). The independent observers could not differentiate patients with common migraine from controls. Evoked potentials recorded during a migraine attack in patients with common migraine were virtually indistinguishable from their records obtained during headache free intervals and from controls (Fig. 2). Three patients (Cases 2,3,4) were tested during the visual aura. In each case the hemisphere contralateral to the visual field defect showed suppression of the first three components of the visual evoked potential (P1, N1 and P2) (Fig. 3 & 4). In two of the patients, two of these components were completely abolished and the waveform was essentially fiat for the first 125 to 135 msec. In the third case, P1 was abolished and N1 and P2 were ill defined with amplitude suppression of 70%. Four patients (Cases 1,2,3,4) were also examined when headache free. In two cases no significant asymmetries were present. In one patient a moderate asymmetry was noted with regard to the first three components and in the fourth patient marked asymmetries were seen although the patient was symptom free (Case 4). The hemisphere exhibiting disorganization and flattening of the early components of the visual evoked potential was in both cases the hemisphere contralateral to the symptomatic side during the attack. DISCUSSION After G. D. Dawson perfected a technique for recording cerebral action potentials it became feasible to estimate nerve conduction in man's central nervous system.2 A delay of cortical responses on stimulation either of a peripheral nerve or in visual potentials maybe evidence of delay in conduction velocity within the brain of
the subject. The results of the present study showed that patients with lateralized visual symptoms have marked interhemispheric asymmetry of visual evoked responses. Whether those with a sensory aura might show similar asymmetries in the evoked potential to touch or pain has, to our knowledge, not been established. It is particularly appropriate that in each of our patients the clinically affected hemisphere was the one which was responsible for the asymmetry. The mechanism of the suppres-
sion of the earlier components of the evoked potentials is not clear but their selective involvement supports the hypothesis of the functional independence of these components of the visual evoked potential. It is probably facile to attribute the observed changes to ischemia, though this has been a fashionable explanation for transient neurologic deficits observed during the migrainous attack. In reviewing the evidence that vasoconstriction occurs during the aura which causes focal symptoms, O'Brien3 pointed out several inconsistencies in this classical theory. In fact, no direct evidence for focal vasoconstriction has so far been found. On the contrary, some evidence exists which suggest that vasoconstriction is widespread and this is based on a number of clinical reports and on cerebral blood flow studies. Skinhøj and Paulson4 showed that a considerable reduction of blood flow in one hemisphere occurred during a prodrome. The greatest reduction in blood flow, however, corresponding to an area of the brain to which the symptoms were attributed. In measuring cortical blood flow bilaterally in 7 patients during prodrome O'Brien5 found a mean reduction in both hemispheres of about 20% and no relationship between changes in blood flow and in the area of the brain which caused the symptoms in his patients. It is also far from clear whether the focal symptoms seen during an aura are caused by vasoconstriction. Some support for this interpretation comes from the disappearance of symptoms when patients inhale 5% carbon dioxide or take amyl nitrite, both powerful cerebral vasodilators. Moreover, a return of symptoms can be observed after giving enough amyl nitrite to produce a fall in systemic pressure. On the other hand, symptoms often begin in the visual cortex and progress slowly over the parietal lobe to the central cortical region. This is a path which is predominantly cortical and is not related to any distinct anatomic area of vascular supply. Also the suppression of the visual evoked potentials in our patients simultaneously in occipital and parietal areas at a time when symptoms were referable to the occipital area would seem to argue against a simple vasoconstrictor mechanism. Moreover, a degree of vasoconstriction capable of producing symptoms during a migrainous aura requires almost certainly an associated patchy necrosis of the brain and this is hardly in keeping with the relative lack of permanent neurological sequelae in migraineurs. A review of patients with hemiplegic migraine showed that any region of the brain can give rise to symptoms and that this is not confined to the supply territory of one artery and on occasion both hemispheres are affected with varying localization during a single attack.6 The presence of fortification illusion during an attack of ophthalmic migraine has been studied recently.7 It was found that the fortification patterns increase towards the periphery of the visual field and this would be consistent with observations on the receptive fields in the visual cortex of animals. The representation is retinotopic because the fortification patterns move to new positions with respect to objects in the environment when the eyes are moved, similar to phosphenes which are produced by electric stimulation of the visual cortex. Moreover, the reduced contrast in the fortification area observed by the victims suggest a cortical mechanism for contrast enhancement which might be normally operative in the visual system so that during an attack the effect of lateral inhibition which usually provides improved contrast is temporarily removed. These observations would also suggest that during the migrainous aura an active disturbance occurs in a functional rather than in an anatomic system which is defined by its blood supply. Previous studies of visual evoked responses in migraineurs during headache free intervals suggested that altered cerebral responses to visual stimulations can be found.8 These, however, were difficult to recognize on inspection and were found on statistical analysis only. Thus, of 3 occipital negative components of the evoked potential, the second had a tendency to appear slightly earlier in the migrainous subjects, whereas, the third appeared somewhat later. A slightly average lower amplitude of the second major surface positive wave was
also found. These differences were significant for the total experimental population and particularly for females. No differences were recognized for male migraineurs. In six patients who had visual defects during the aura but who were studied during a headache free interval, no significant differences from the total group in evoked visual potentials were found. Utilizing a complicated procedure which allowed the separate stimulation of left and right half of the visual fields, Reagan and Heron.9 found significant asymmetries which were accentuated during an attack in three of five migraineurs when compared to controls. Our results obtained by simpler methods support the earlier findings. An aspect of the present study was the asymmetry in visual evoked responses in two classic migraineurs in the absence of clinical evidence of dysfunction of the visual system. This is similar to the high incidence of delayed visual pattern evoked responses in multiple sclerosis patients without clinical damage to the visual pathways.10 Though abnormalities in visual evoked responses are not specific for any particular disease, they might provide evidence of persistent dysfunction of the nervous system in migraine. This is perhaps analogous to persistent abnormalities in vasomotor control found in hands of migraineurs during headache free intervals.11,12 The presence of recognizable abnormalities in untreated patients might also give a useful objective measure of the efficacy of drugs for prophylaxis and for the treatment of the migrainous attack. Hitherto, in assessing the value of headache remedies, it was the patient's report rather than improvement in cortical evoked activity which was the yardstick of success. SUMMARY The electrical responses of the cortex to flashes presented to the eyes were recorded in 8 migrainous patients and 5 non-migrainous controls. Four of the migraine patients had classic migraine. All patients except one were tested both during a migrainous attack and during a headache free interval. During the visual aura the hemisphere contralateral to the field defect showed suppression of the first three components of the visual evoked responses. In two of these patients, asymmetries were noted during headache free intervals also. Patients with common migraine could not be differentiated from controls either during an attack or while headache free. It appears that visual evoked responses might be useful in identifying classic migraineurs and perhaps in monitoring the efficacy of headache remedies. REFERENCES 1. Wolff's Headache and Other Head Pain. Revised by Dalessio, D.J. 3rd edition. Oxford University Press, New York, 1972. 2. Dawson GD: Cerebral responses to electrical stimulation of peripheral nerve in man. Journal of Neurology, Neurosurgery and Psychiatry 10: 137-140, 1947. 3.
O'Brien MD: The haemodynamics of migraine - a review. Headache 12: 1160-162, 1973.
4. Skinhøj E and Paulson OB: Regional blood flow in internal carotid distribution during migraine attack. British Medical Journal 3:569-570, 1969. 5. O'Brien MD: The relationship between aura symptoms and cerebral blood flow changes in the prodrome of migraine. Headache 11: 90-91, 1971. 6.
Heyck H: Varieties of hemiplegic migraine. Headache 12: 135-142, 1973.
7. Pöppel E: Fortification illusion during an attack of ophthalmic migraine. Implications for the human visual cortex. Die Naturwissen-schaften 60: 554-555, 1973. 8. Richey ET, Kooi KA and Waggoner RW: Visually evoked responses in migraine. Electroencephalography and Clinical Neurophysiology 21: 23-27, 1966. 9. Regan D and Heron JR: Simultaneous recording of visual evoked potentials from the left and right hemispheres in migraine. In Background to Migraine. Heinemann, London, pp 66-77, 1970. 10. Halliday AM, McDonald WI and Mushin J: visual evoked response in diagnosis of multiple sclerosis. British Medical Journal 4: 661-664, 1973. 11. Appenzeller O, Davison K and Marshall J: Reflex vasomotor abnormalities in the hands of migrainous subjects. Journal of Neurology, Neurosurgery and Psychiatry 26: 447-450, 1963. 12. Elliott K, Frewin DB and Downey JA: Reflex vasomotor responses in the hands of patients suffering from migraine. Headache 13: 188-196, 1974. Address reprint requests to: Otto Appenzeller. M.D. Univ. of New Mexico. Dept. of Neurology 1007 Stanford Dr. NE, Albuquerque, NM 87131
TABLE I Age, Duration of Aura Case Yrs. Sex Migraine (yrs.) Visual Transient Neurologic Deficits EEG I 19 F l1 Yes No Normal 2 23 F l0 Yes Hemisensory Deficit Diffuse slowing 3 24 F 14 Yes Dysphasia; Hemisensory Deficit Normal 4 30 F 15 Yes Dysphasia; Hemisensory Deficit Normal 5 49 F 15 No No Diffuse slowing 6 26 F 1 No No Normal 7 25 F 20 No No Diffuse slowing Slight asymmetry 8 27 M 14 No No Normal involved with equal frequency. The third patient, however, had right sided headaches only. This patient had, simultaneously with the pain, ipsilateral visual deficits. EEG and brain scan in this patient were normal (Case 4). All subjects were medication free for two days prior to the tests. The procedure was explained and they were informed of the artifacts produced by muscle tension, eye movement, and changes in body position. A brief period of adaptation to the experimental situation during which artifacts could be assessed and eliminated preceded the actual tests. APPARATUS AND PRODEDURE Subjects were seated in a darkened room with the head toward the center of a stainless steel hemisphere, the distance from the nasion to a point in the center of the hemisphere being 30cm. The hemisphere was non-reflecting white in color and measured 78cm. in diameter. It was illuminated by a Grass PS2 photo-stimulator (intensity 16) which was positioned above the subject's head. The subject's eyes were closed. In each test session 100 flashes were presented at random intervals of 2 to 5 seconds. The EEG was recorded at standard settings on a Grass Model 78 polygraph with electrodes placed on the scalp. Ipsilateral ear references to parietal and occipital electrodes were used. The EEG was also recorded on a Honeywell 5600 analogue tape deck and continually monitored by a Tektronix Type 502A dual beam oscilloscope. The photic stimulation acted as a marker and triggered a link-8 computer which digitized and averaged the EEG for each 512 msec period after a flash. Each averaged evoked response with its standard deviation was displayed on the oscilloscope of the computer. The tabulation of latency and amplitude of the various components of the waveform was accomplished through the display of the X-Y coordinates corresponding to the position of a moveable cursor. A photograph was taken of each response. These photographs were later presented to two judges not involved in the study. They were asked to identify, from photographs, subjects with interhemispheric differences. All patients except case 1 were tested both during a migraine attack and a headache free interval. Control subjects were tested on one occasion only. RESULTS The typical evoked potentials were sinusoidal multiphasic waves with five components (Fig. 1). The earliest positive deflection (P1) had an onset time of 50 to 75 msec. After this a negative deflection (N1) occurred between 60 and 90 msec. later. A larger positive deflection (P2) was found after 80-100 msec. and a still larger negative component (N2) at 125 to 140 msec. Finally a large enduring positive deflection (P3) occurred between 179 and
200 msec. This component was usually succeeded by an after discharge of 10 to 12 hz. A separation of patients into two groups by two independent observers was achieved (100% correct). The degree of interhemispheric asymmetries distinguished all classic migraineurs tested during the aura. This group was also correctly separated into whether they were during an attack of migraine or headache free. One patient, however, showed marked asymmetries during both attack and headache free period (Case 4). The independent observers could not differentiate patients with common migraine from controls. Evoked potentials recorded during a migraine attack in patients with common migraine were virtually indistinguishable from their records obtained during headache free intervals and from controls (Fig. 2). Three patients (Cases 2,3,4) were tested during the visual aura. In each case the hemisphere contralateral to the visual field defect showed suppression of the first three components of the visual evoked potential (P1, N1 and P2) (Fig. 3 & 4). In two of the patients, two of these components were completely abolished and the waveform was essentially fiat for the first 125 to 135 msec. In the third case, P1 was abolished and N1 and P2 were ill defined with amplitude suppression of 70%. Four patients (Cases 1,2,3,4) were also examined when headache free. In two cases no significant asymmetries were present. In one patient a moderate asymmetry was noted with regard to the first three components and in the fourth patient marked asymmetries were seen although the patient was symptom free (Case 4). The hemisphere exhibiting disorganization and flattening of the early components of the visual evoked potential was in both cases the hemisphere contralateral to the symptomatic side during the attack. DISCUSSION After G. D. Dawson perfected a technique for recording cerebral action potentials it became feasible to estimate nerve conduction in man's central nervous system.2 A delay of cortical responses on stimulation either of a peripheral nerve or in visual potentials maybe evidence of delay in conduction velocity within the brain of
the subject. The results of the present study showed that patients with lateralized visual symptoms have marked interhemispheric asymmetry of visual evoked responses. Whether those with a sensory aura might show similar asymmetries in the evoked potential to touch or pain has, to our knowledge, not been established. It is particularly appropriate that in each of our patients the clinically affected hemisphere was the one which was responsible for the asymmetry. The mechanism of the suppres-
sion of the earlier components of the evoked potentials is not clear but their selective involvement supports the hypothesis of the functional independence of these components of the visual evoked potential. It is probably facile to attribute the observed changes to ischemia, though this has been a fashionable explanation for transient neurologic deficits observed during the migrainous attack. In reviewing the evidence that vasoconstriction occurs during the aura which causes focal symptoms, O'Brien3 pointed out several inconsistencies in this classical theory. In fact, no direct evidence for focal vasoconstriction has so far been found. On the contrary, some evidence exists which suggest that vasoconstriction is widespread and this is based on a number of clinical reports and on cerebral blood flow studies. Skinhøj and Paulson4 showed that a considerable reduction of blood flow in one hemisphere occurred during a prodrome. The greatest reduction in blood flow, however, corresponding to an area of the brain to which the symptoms were attributed. In measuring cortical blood flow bilaterally in 7 patients during prodrome O'Brien5 found a mean reduction in both hemispheres of about 20% and no relationship between changes in blood flow and in the area of the brain which caused the symptoms in his patients. It is also far from clear whether the focal symptoms seen during an aura are caused by vasoconstriction. Some support for this interpretation comes from the disappearance of symptoms when patients inhale 5% carbon dioxide or take amyl nitrite, both powerful cerebral vasodilators. Moreover, a return of symptoms can be observed after giving enough amyl nitrite to produce a fall in systemic pressure. On the other hand, symptoms often begin in the visual cortex and progress slowly over the parietal lobe to the central cortical region. This is a path which is predominantly cortical and is not related to any distinct anatomic area of vascular supply. Also the suppression of the visual evoked potentials in our patients simultaneously in occipital and parietal areas at a time when symptoms were referable to the occipital area would seem to argue against a simple vasoconstrictor mechanism. Moreover, a degree of vasoconstriction capable of producing symptoms during a migrainous aura requires almost certainly an associated patchy necrosis of the brain and this is hardly in keeping with the relative lack of permanent neurological sequelae in migraineurs. A review of patients with hemiplegic migraine showed that any region of the brain can give rise to symptoms and that this is not confined to the supply territory of one artery and on occasion both hemispheres are affected with varying localization during a single attack.6 The presence of fortification illusion during an attack of ophthalmic migraine has been studied recently.7 It was found that the fortification patterns increase towards the periphery of the visual field and this would be consistent with observations on the receptive fields in the visual cortex of animals. The representation is retinotopic because the fortification patterns move to new positions with respect to objects in the environment when the eyes are moved, similar to phosphenes which are produced by electric stimulation of the visual cortex. Moreover, the reduced contrast in the fortification area observed by the victims suggest a cortical mechanism for contrast enhancement which might be normally operative in the visual system so that during an attack the effect of lateral inhibition which usually provides improved contrast is temporarily removed. These observations would also suggest that during the migrainous aura an active disturbance occurs in a functional rather than in an anatomic system which is defined by its blood supply. Previous studies of visual evoked responses in migraineurs during headache free intervals suggested that altered cerebral responses to visual stimulations can be found.8 These, however, were difficult to recognize on inspection and were found on statistical analysis only. Thus, of 3 occipital negative components of the evoked potential, the second had a tendency to appear slightly earlier in the migrainous subjects, whereas, the third appeared somewhat later. A slightly average lower amplitude of the second major surface positive wave was
also found. These differences were significant for the total experimental population and particularly for females. No differences were recognized for male migraineurs. In six patients who had visual defects during the aura but who were studied during a headache free interval, no significant differences from the total group in evoked visual potentials were found. Utilizing a complicated procedure which allowed the separate stimulation of left and right half of the visual fields, Reagan and Heron.9 found significant asymmetries which were accentuated during an attack in three of five migraineurs when compared to controls. Our results obtained by simpler methods support the earlier findings. An aspect of the present study was the asymmetry in visual evoked responses in two classic migraineurs in the absence of clinical evidence of dysfunction of the visual system. This is similar to the high incidence of delayed visual pattern evoked responses in multiple sclerosis patients without clinical damage to the visual pathways.10 Though abnormalities in visual evoked responses are not specific for any particular disease, they might provide evidence of persistent dysfunction of the nervous system in migraine. This is perhaps analogous to persistent abnormalities in vasomotor control found in hands of migraineurs during headache free intervals.11,12 The presence of recognizable abnormalities in untreated patients might also give a useful objective measure of the efficacy of drugs for prophylaxis and for the treatment of the migrainous attack. Hitherto, in assessing the value of headache remedies, it was the patient's report rather than improvement in cortical evoked activity which was the yardstick of success. SUMMARY The electrical responses of the cortex to flashes presented to the eyes were recorded in 8 migrainous patients and 5 non-migrainous controls. Four of the migraine patients had classic migraine. All patients except one were tested both during a migrainous attack and during a headache free interval. During the visual aura the hemisphere contralateral to the field defect showed suppression of the first three components of the visual evoked responses. In two of these patients, asymmetries were noted during headache free intervals also. Patients with common migraine could not be differentiated from controls either during an attack or while headache free. It appears that visual evoked responses might be useful in identifying classic migraineurs and perhaps in monitoring the efficacy of headache remedies. REFERENCES 1. Wolff's Headache and Other Head Pain. Revised by Dalessio, D.J. 3rd edition. Oxford University Press, New York, 1972. 2. Dawson GD: Cerebral responses to electrical stimulation of peripheral nerve in man. Journal of Neurology, Neurosurgery and Psychiatry 10: 137-140, 1947. 3.
O'Brien MD: The haemodynamics of migraine - a review. Headache 12: 1160-162, 1973.
4. Skinhøj E and Paulson OB: Regional blood flow in internal carotid distribution during migraine attack. British Medical Journal 3:569-570, 1969. 5. O'Brien MD: The relationship between aura symptoms and cerebral blood flow changes in the prodrome of migraine. Headache 11: 90-91, 1971. 6.
Heyck H: Varieties of hemiplegic migraine. Headache 12: 135-142, 1973.
7. Pöppel E: Fortification illusion during an attack of ophthalmic migraine. Implications for the human visual cortex. Die Naturwissen-schaften 60: 554-555, 1973. 8. Richey ET, Kooi KA and Waggoner RW: Visually evoked responses in migraine. Electroencephalography and Clinical Neurophysiology 21: 23-27, 1966. 9. Regan D and Heron JR: Simultaneous recording of visual evoked potentials from the left and right hemispheres in migraine. In Background to Migraine. Heinemann, London, pp 66-77, 1970. 10. Halliday AM, McDonald WI and Mushin J: visual evoked response in diagnosis of multiple sclerosis. British Medical Journal 4: 661-664, 1973. 11. Appenzeller O, Davison K and Marshall J: Reflex vasomotor abnormalities in the hands of migrainous subjects. Journal of Neurology, Neurosurgery and Psychiatry 26: 447-450, 1963. 12. Elliott K, Frewin DB and Downey JA: Reflex vasomotor responses in the hands of patients suffering from migraine. Headache 13: 188-196, 1974. Address reprint requests to: Otto Appenzeller. M.D. Univ. of New Mexico. Dept. of Neurology 1007 Stanford Dr. NE, Albuquerque, NM 87131
