The blink reflex in migraine
J Bánk, E Bense, Cs Király
County Hospital, Neurology Unit, Debrecen, Hungary Cephalalgia
Bánk J, Bense E, Király Cs. The Blink reflex in migraine. Cephalalgia Oslo. ISSN 0333-1024 The blink reflex is an objective and useful method to study the trigeminal system. It was recorded in 43 migraine patients and the findings compared with those of 31 healthy controls. The latencies of the R1 component were in the normal range in both groups. The R2 latencies ranged between 30 and 32 ms in the control group. In contrast, more than half of the patients with migraine had R2 latencies between 32 and 35 ms in the migraine group. Some migraine patients had latencies above 35 ms. The R2 latency was statistically significantly different between controls and migraineurs (p < 0.0001). Our findings indicate that trigeminal afferents and/or polysynaptic pathway in brainstem may be altered in migraine. • Blink reflex, dysfunction of brainstem, migraine, polysynaptic pathway J Bánk, County Hospital, Neurology Unit, Debrecen, Hungary. Received 5 February 1992, accepted 18 June 1992
The brainstem and its trigeminovascular connections may play a role in the pathogenesis of migraine (1-5). For this reason investigators have employed evoked potentials in order to assess brainstem function in this disorder. These studies have indicated abnormalities in somatosensory evoked potentials (6, 7) but brainstem auditory evoked potential (BAEP) recording, a particularly sensitive tool for the assessment of brainstem function, has yielded contradictory results (8-11). Another well-known tool for the investigation of brainstem function is the blink reflex. The mechanically or electrically elicited blink reflex resembles the corneal reflex tested in clinical practice (12-14). Stimulation of the supraorbital nerve elicits two temporally separate responses of the orbicularis oculi, an early (R1) component and a late (R2) component. Of the two, R1 is evoked only on the side of stimulation via a pontine pathway (14). In contrast, unilateral stimulation elicits R2 bilaterally, presumably relayed through a more complex route, including the pons and lateral medulla (15-17). The blink reflex can be an objective and useful method for studying the trigeminal system. To our knowledge, only patients with cluster headache have been investigated in this manner (18-21). The purpose of this study was to examine the blink reflex in migraine patients. Differences in latencies (R1 and R2 ) were calculated and compared with those of healthy controls. Subjects and methods
Forty-three subjects (14M, 29F) with a mean age of 31.1 ± 9.6 (range 13-67) were studied. Patients were diagnosed according to the criteria of the International Headache Society (22). Thirty-three suffered from migraine without aura and 10 from migraine with aura. The findings were compared with those of 31 healthy controls (22F, 9M) with a mean age of 22.7 ± 7.4 (range 15-44). All subjects underwent a standardized interview as well as a clinical neurological examination. Subjects with lesions of the trigeminal nerve, Bell's palsy, polyneuropathy, multiple sclerosis, facial hypoesthesia, synkinesis of facial muscles, Wallenberg syndrome, acoustic neuroma or any other neurological disorders were excluded. At the time of the investigation all patients were symptom-free and had received no medication in the previous 14 days. The blink reflex was recorded using Amplaid EMG 15 (Madaus Elektronik). Informed consent was obtained after the nature of the procedure had been fully explained to the subjects. Subjects sat in an armchair in a warm, quiet room with the eyes closed. Surface recording electrodes were placed on the lower lateral aspect of the orbicularis oculi, reference electrodes were placed on the lateral surface of the nose, and the ground electrode was placed around the arm. The supraorbital nerve was stimulated with the cathode placed over the supraorbital foramen. The same intensity of stimulation was used on both sides in each subject. The stimulation rate for obtaining the blink reflex was 1/s. Four responses were studied in each subject. The shortest latency was taken into account and the EMG was not rectified. We evaluated the latencies of R1 and R2 waves in the migraine patients and control subjects. Statistical analysis was performed using the chi-square test. We formed four clusters according to R2 latency distribution (28-30, 30-32, 32-34, 34-ms). We evaluated differences between migraine patients and controls separately for right and left sides. Results
Illustrative samples of the blink reflex recording in a migraineur and a control subject are shown in Fig. 1.
We first evaluated the latencies of R1 waves in both groups. Statistical analysis failed to show significant differences between the two groups. No asymmetry of the ipsilateral or contralateral R2 latencies were observed in either migraine patients or controls after stimulation of the right or left supraorbital nerve. The average values and distribution of R2 latencies are given in Figs. 2 and 3, respectively, for the migraineurs and controls. The latencies of the R2 waves were shorter in the control group than in the migraine patients. The majority of controls had the R2 latencies between 30 and 32 ms. We did not measure latencies of R2 above 33 ms in healthy controls. In contrast, more than half of the migraine patients had R2 latencies between 32 and 35 ms. Some patients had latencies above 35 ms (Fig. 3). The difference in R2 wave latencies between controls and migraineurs was statistically significant (X2= 22.5 right, 22.9 left. p < 0.0001). Discussion
Blink reflex abnormalities can be categorized into either afferent or efferent types based on the analysis of the R2 component. The latency of R1 represents the conduction time along the trigeminal and facial nerves and pontine relay. Our results signify that this oligosynaptic pathway is intact in migraine patients. It seems clear that R1 is a more reliable and constant wave. The latency of R2 reflects the excitability of interneurons and delay introduced by synaptic transmission in addition to the axonaI conduction time. The delay of R2 was significantly greater in migraine patients. The reasons for this delay are uncertain, especially in a headache-free interval. EEG and evoked potential abnormalities have been previously reported in headache-free migraineurs. Interictal EEG abnormalities were found in 20-55% of migraine patients in different series (23). Prolongation of the P2 wave in visual evoked potentials obtained in migraine subjects has been ascribed to either "ischemic or synaptic damage due to a neurotransmitter derangement" (24). The fact that EEG and evoked potential abnormalities can be detected between migraine attacks when there is no headache and no vasomotor changes lends support to a difference in CNS function in susceptible patients (25). A polygenic inherited defect involving elements such as the monoamine neurotransmitters, transduction systems, neuropeptides etc. has been postulated in migraine patients (26). In consequence these defects modify the migraine threshold so that factors such as mood changes, excessive afferent stimuli or circadian rhythms may influence brainstem structures that project to the cerebral cortex causing constriction of the microcirculation and possibly spreading depression with associated neurological symptoms (26). The polysynaptic transduction system that is involved in the blink reflex appears to be altered in migraine. This slight functional brainstem abnormality may underline or be the basis of migraine susceptibility. On the other hand, a peripheral abnormality of the trigeminal afferents could play a part in the findings presented here. Sensory deficits of the face often cause R2 latency alteration. In these cases, clinical evaluation may have failed to detect minor sensory deficits (27). Pharmacological modulation of the blink reflex also needs to be considered. For example studies have shown absent R2 with normal or nearly normal R1 in alert patients given therapeu-
tic dosages of diazepam, which presumably blocks the multisynaptic reflex arc (28). None of our patients had taken medication for 14 days, however. Complex psychologic events may also selectively affect different reflex pathways (29). The blink reflex is one of the polysynaptic reflexes elicited by exteroceptive stimuli that are markedly susceptible to habituation in man. In contrast, exteroceptive suppression of the masseter muscle, another polysynaptic brainstem reflex, only reveals slight habituation of the late component and no habituation of the early component (30.). The latter poly-synaptic reflex is normal in headache-free migraineurs. Taken together, our findings may indicate that trigeminal afferents and polysynaptic pathways or both may be altered in migraine. References
1.
Fozard JR. 5-Hydroxytryptamine in the pathophysiology of migraine. In: Bevan JA, Godfraind T, Maxwell RA, Stoclet JC, Worcel M eds Vascular neuroeffector mechanisms. Amsterdam: Elsevier, 1985:321-8
2.
Lance JW. Mechanism and management of headache, 4th edn. London: Butterworths, 1982
3.
Lance JW. The pathophysiology of migraine. Ann Acad Med 1985:14:4-11
4.
Moskowitz MA. The neurobiology of vascular head pain. Ann Neurol 1984;6:157-68
5.
Pearce JMS. Migraine: a cerebral disorder. Lancet 1984; ii:86-9
6.
Montagna P, Zucconi M, Zappia M, Liguori R. Somatosensory evoked potentials in migraine and tension headache. Headache 1985;25:115
7.
Milone F, D'Andrea G, Canazi AR, Zani R. Somatosensory evoked potential patterns in migraine sufferers. Cephalalgia 1985;5(suppl 3):34-5
8.
Podoshin L, Ben-David J, Pratt H, Fradis M, Sharf B, Weller B, Wajsbort J, Zellinger M. Auditory brainstem evoked potentials in patients with migraine. Headache 1988;28: 204-6
9.
Battistella PA, Suppiej A, Casara G, Cavinato MS, Olivotto D, Pitassi I, Zachello F. Brainstem auditory evoked potentials (BAEPS) in childhood migraine. Headache 1988;28: 204 - 6
10.
Benna P, Bianco C, Costa P, Piazza D, Bergamasco B. Visual evoked potentials and brainstem evoked potentials in mi-graine and transient ischemic attacks. Cephalalgia 1985; 5(suppl 2):53-8
11.
Bussone G, Sinatra MG, Bioardi A, La Mantia L, Frediani F, Cocchini F. Brainstem auditory evoked potentials in mi-graine patients in basal conditions and after chronic flunarizine treatment. Cephalalgia 1985;5(suppl 2):177-80
12.
Kugelberg E. Facial reflexes. Brain 1952;75:385-96
13.
Kimura J, Powers JM, Van Allen MW. Reflex response of orbicularis oculi muscle to supraorbital nerve stimulation: study in normal subjects and in peripheral facial paresis. Arch Neurol 1969;21:193-9
14.
Shahani BT, Young RR. Human orbicularis oculi reflexes. Neurology 1972;22:149-54
15.
Csécsei, G. Facial afferent fibers in the blink reflex of man. Brain Res 1979:161:347-50
16.
Hiraoka M, Shimamura M Neural mechanisms of the corneal blinking reflex in cats. Brain Res 1977;125:265-75
17.
Kimura J, Lyon LW. Orbicularis oculi reflex in the Wallenberg syndrome: alteration of the late reflex by lesions of the spinal tract and nucleus of the trigeminal nerve. J Neurol Neurosurg Psychiatry 1972;35:228-33
18.
Pavesi G, Granella F, Brambilla S, Medici D, Mancia D, Manzoni GC. Blink reflex in cluster headache: evidence of a trigeminal system dysfunction. Cephalalgia 1987;7(suppl 6):100-2
19.
Sandrini G, Alfonsi E, Ruiz L, Micieli G, Moglia A, Nappi G. Electrophysiological study of trigeminal-facial reflexes in cluster headache. Electroencephalogr Clin Neurophysiol 1989:72-81P
20.
Formisano R, Cerbo R, Ricci M, Agostino R, Cesarino F, Gruccu G, Agnoli A. Blink reflex in cluster headache. Cephalalgia 1987;7(suppl 6):353-4
21.
Francesco Raudino. The blink reflex in cluster headache. Headache 1990;9:584-5
22.
Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988;8:(suppl 7)
23.
Parsonage MJ. Electroencephalographic studies in migraine. In: Pearce J ed Modern topics in migraine. London: Heinemann Medical 1975:72-84
24.
Kennard C, Gawel M, Rudolph M, Rose CF. Visual evoked potentials in migraine subjects. Res Clin Stud Headache 1978;6:73-80
25.
Blau JN. Migraine pathogenesis: the neural hypothesis reexamined. J Neurol Neurosurg Psychiatry 1984;47:437-42
26.
Lance JW. A concept of migraine and the search for the ideal headache drug. Headache 1990;30(suppl 1):17-23
27.
Kimura J. Electrodiagnosis in diseases of nerve and muscle: principles and practice, 2nd ed. 1989
28.
Kimura J. The blink reflex as a test for brainstem and higher central nervous system functions. In: Desmedt JE ed New developments in electromyography and clinical neurophysiology, vol 3. Basel: Karger, 1973:682-91
29.
Sanes JN, Foss JA, Ison JR. Conditions that affect the thresholds of the components of the eyeblink reflex in humans. J Neurol Neurosurg Psychiatry 1982;45:543-9
30.
Desmedt JE, Godaux E. Habituation of exteroceptive suppression and of exteroceptive reflexes in man as influenced by voluntary contraction. Brain Res 1976;106:21-9
J Bánk, E Bense, Cs Király
County Hospital, Neurology Unit, Debrecen, Hungary Cephalalgia
Bánk J, Bense E, Király Cs. The Blink reflex in migraine. Cephalalgia Oslo. ISSN 0333-1024 The blink reflex is an objective and useful method to study the trigeminal system. It was recorded in 43 migraine patients and the findings compared with those of 31 healthy controls. The latencies of the R1 component were in the normal range in both groups. The R2 latencies ranged between 30 and 32 ms in the control group. In contrast, more than half of the patients with migraine had R2 latencies between 32 and 35 ms in the migraine group. Some migraine patients had latencies above 35 ms. The R2 latency was statistically significantly different between controls and migraineurs (p < 0.0001). Our findings indicate that trigeminal afferents and/or polysynaptic pathway in brainstem may be altered in migraine. • Blink reflex, dysfunction of brainstem, migraine, polysynaptic pathway J Bánk, County Hospital, Neurology Unit, Debrecen, Hungary. Received 5 February 1992, accepted 18 June 1992
The brainstem and its trigeminovascular connections may play a role in the pathogenesis of migraine (1-5). For this reason investigators have employed evoked potentials in order to assess brainstem function in this disorder. These studies have indicated abnormalities in somatosensory evoked potentials (6, 7) but brainstem auditory evoked potential (BAEP) recording, a particularly sensitive tool for the assessment of brainstem function, has yielded contradictory results (8-11). Another well-known tool for the investigation of brainstem function is the blink reflex. The mechanically or electrically elicited blink reflex resembles the corneal reflex tested in clinical practice (12-14). Stimulation of the supraorbital nerve elicits two temporally separate responses of the orbicularis oculi, an early (R1) component and a late (R2) component. Of the two, R1 is evoked only on the side of stimulation via a pontine pathway (14). In contrast, unilateral stimulation elicits R2 bilaterally, presumably relayed through a more complex route, including the pons and lateral medulla (15-17). The blink reflex can be an objective and useful method for studying the trigeminal system. To our knowledge, only patients with cluster headache have been investigated in this manner (18-21). The purpose of this study was to examine the blink reflex in migraine patients. Differences in latencies (R1 and R2 ) were calculated and compared with those of healthy controls. Subjects and methods
Forty-three subjects (14M, 29F) with a mean age of 31.1 ± 9.6 (range 13-67) were studied. Patients were diagnosed according to the criteria of the International Headache Society (22). Thirty-three suffered from migraine without aura and 10 from migraine with aura. The findings were compared with those of 31 healthy controls (22F, 9M) with a mean age of 22.7 ± 7.4 (range 15-44). All subjects underwent a standardized interview as well as a clinical neurological examination. Subjects with lesions of the trigeminal nerve, Bell's palsy, polyneuropathy, multiple sclerosis, facial hypoesthesia, synkinesis of facial muscles, Wallenberg syndrome, acoustic neuroma or any other neurological disorders were excluded. At the time of the investigation all patients were symptom-free and had received no medication in the previous 14 days. The blink reflex was recorded using Amplaid EMG 15 (Madaus Elektronik). Informed consent was obtained after the nature of the procedure had been fully explained to the subjects. Subjects sat in an armchair in a warm, quiet room with the eyes closed. Surface recording electrodes were placed on the lower lateral aspect of the orbicularis oculi, reference electrodes were placed on the lateral surface of the nose, and the ground electrode was placed around the arm. The supraorbital nerve was stimulated with the cathode placed over the supraorbital foramen. The same intensity of stimulation was used on both sides in each subject. The stimulation rate for obtaining the blink reflex was 1/s. Four responses were studied in each subject. The shortest latency was taken into account and the EMG was not rectified. We evaluated the latencies of R1 and R2 waves in the migraine patients and control subjects. Statistical analysis was performed using the chi-square test. We formed four clusters according to R2 latency distribution (28-30, 30-32, 32-34, 34-ms). We evaluated differences between migraine patients and controls separately for right and left sides. Results
Illustrative samples of the blink reflex recording in a migraineur and a control subject are shown in Fig. 1.
We first evaluated the latencies of R1 waves in both groups. Statistical analysis failed to show significant differences between the two groups. No asymmetry of the ipsilateral or contralateral R2 latencies were observed in either migraine patients or controls after stimulation of the right or left supraorbital nerve. The average values and distribution of R2 latencies are given in Figs. 2 and 3, respectively, for the migraineurs and controls. The latencies of the R2 waves were shorter in the control group than in the migraine patients. The majority of controls had the R2 latencies between 30 and 32 ms. We did not measure latencies of R2 above 33 ms in healthy controls. In contrast, more than half of the migraine patients had R2 latencies between 32 and 35 ms. Some patients had latencies above 35 ms (Fig. 3). The difference in R2 wave latencies between controls and migraineurs was statistically significant (X2= 22.5 right, 22.9 left. p < 0.0001). Discussion
Blink reflex abnormalities can be categorized into either afferent or efferent types based on the analysis of the R2 component. The latency of R1 represents the conduction time along the trigeminal and facial nerves and pontine relay. Our results signify that this oligosynaptic pathway is intact in migraine patients. It seems clear that R1 is a more reliable and constant wave. The latency of R2 reflects the excitability of interneurons and delay introduced by synaptic transmission in addition to the axonaI conduction time. The delay of R2 was significantly greater in migraine patients. The reasons for this delay are uncertain, especially in a headache-free interval. EEG and evoked potential abnormalities have been previously reported in headache-free migraineurs. Interictal EEG abnormalities were found in 20-55% of migraine patients in different series (23). Prolongation of the P2 wave in visual evoked potentials obtained in migraine subjects has been ascribed to either "ischemic or synaptic damage due to a neurotransmitter derangement" (24). The fact that EEG and evoked potential abnormalities can be detected between migraine attacks when there is no headache and no vasomotor changes lends support to a difference in CNS function in susceptible patients (25). A polygenic inherited defect involving elements such as the monoamine neurotransmitters, transduction systems, neuropeptides etc. has been postulated in migraine patients (26). In consequence these defects modify the migraine threshold so that factors such as mood changes, excessive afferent stimuli or circadian rhythms may influence brainstem structures that project to the cerebral cortex causing constriction of the microcirculation and possibly spreading depression with associated neurological symptoms (26). The polysynaptic transduction system that is involved in the blink reflex appears to be altered in migraine. This slight functional brainstem abnormality may underline or be the basis of migraine susceptibility. On the other hand, a peripheral abnormality of the trigeminal afferents could play a part in the findings presented here. Sensory deficits of the face often cause R2 latency alteration. In these cases, clinical evaluation may have failed to detect minor sensory deficits (27). Pharmacological modulation of the blink reflex also needs to be considered. For example studies have shown absent R2 with normal or nearly normal R1 in alert patients given therapeu-
tic dosages of diazepam, which presumably blocks the multisynaptic reflex arc (28). None of our patients had taken medication for 14 days, however. Complex psychologic events may also selectively affect different reflex pathways (29). The blink reflex is one of the polysynaptic reflexes elicited by exteroceptive stimuli that are markedly susceptible to habituation in man. In contrast, exteroceptive suppression of the masseter muscle, another polysynaptic brainstem reflex, only reveals slight habituation of the late component and no habituation of the early component (30.). The latter poly-synaptic reflex is normal in headache-free migraineurs. Taken together, our findings may indicate that trigeminal afferents and polysynaptic pathways or both may be altered in migraine. References
1.
Fozard JR. 5-Hydroxytryptamine in the pathophysiology of migraine. In: Bevan JA, Godfraind T, Maxwell RA, Stoclet JC, Worcel M eds Vascular neuroeffector mechanisms. Amsterdam: Elsevier, 1985:321-8
2.
Lance JW. Mechanism and management of headache, 4th edn. London: Butterworths, 1982
3.
Lance JW. The pathophysiology of migraine. Ann Acad Med 1985:14:4-11
4.
Moskowitz MA. The neurobiology of vascular head pain. Ann Neurol 1984;6:157-68
5.
Pearce JMS. Migraine: a cerebral disorder. Lancet 1984; ii:86-9
6.
Montagna P, Zucconi M, Zappia M, Liguori R. Somatosensory evoked potentials in migraine and tension headache. Headache 1985;25:115
7.
Milone F, D'Andrea G, Canazi AR, Zani R. Somatosensory evoked potential patterns in migraine sufferers. Cephalalgia 1985;5(suppl 3):34-5
8.
Podoshin L, Ben-David J, Pratt H, Fradis M, Sharf B, Weller B, Wajsbort J, Zellinger M. Auditory brainstem evoked potentials in patients with migraine. Headache 1988;28: 204-6
9.
Battistella PA, Suppiej A, Casara G, Cavinato MS, Olivotto D, Pitassi I, Zachello F. Brainstem auditory evoked potentials (BAEPS) in childhood migraine. Headache 1988;28: 204 - 6
10.
Benna P, Bianco C, Costa P, Piazza D, Bergamasco B. Visual evoked potentials and brainstem evoked potentials in mi-graine and transient ischemic attacks. Cephalalgia 1985; 5(suppl 2):53-8
11.
Bussone G, Sinatra MG, Bioardi A, La Mantia L, Frediani F, Cocchini F. Brainstem auditory evoked potentials in mi-graine patients in basal conditions and after chronic flunarizine treatment. Cephalalgia 1985;5(suppl 2):177-80
12.
Kugelberg E. Facial reflexes. Brain 1952;75:385-96
13.
Kimura J, Powers JM, Van Allen MW. Reflex response of orbicularis oculi muscle to supraorbital nerve stimulation: study in normal subjects and in peripheral facial paresis. Arch Neurol 1969;21:193-9
14.
Shahani BT, Young RR. Human orbicularis oculi reflexes. Neurology 1972;22:149-54
15.
Csécsei, G. Facial afferent fibers in the blink reflex of man. Brain Res 1979:161:347-50
16.
Hiraoka M, Shimamura M Neural mechanisms of the corneal blinking reflex in cats. Brain Res 1977;125:265-75
17.
Kimura J, Lyon LW. Orbicularis oculi reflex in the Wallenberg syndrome: alteration of the late reflex by lesions of the spinal tract and nucleus of the trigeminal nerve. J Neurol Neurosurg Psychiatry 1972;35:228-33
18.
Pavesi G, Granella F, Brambilla S, Medici D, Mancia D, Manzoni GC. Blink reflex in cluster headache: evidence of a trigeminal system dysfunction. Cephalalgia 1987;7(suppl 6):100-2
19.
Sandrini G, Alfonsi E, Ruiz L, Micieli G, Moglia A, Nappi G. Electrophysiological study of trigeminal-facial reflexes in cluster headache. Electroencephalogr Clin Neurophysiol 1989:72-81P
20.
Formisano R, Cerbo R, Ricci M, Agostino R, Cesarino F, Gruccu G, Agnoli A. Blink reflex in cluster headache. Cephalalgia 1987;7(suppl 6):353-4
21.
Francesco Raudino. The blink reflex in cluster headache. Headache 1990;9:584-5
22.
Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988;8:(suppl 7)
23.
Parsonage MJ. Electroencephalographic studies in migraine. In: Pearce J ed Modern topics in migraine. London: Heinemann Medical 1975:72-84
24.
Kennard C, Gawel M, Rudolph M, Rose CF. Visual evoked potentials in migraine subjects. Res Clin Stud Headache 1978;6:73-80
25.
Blau JN. Migraine pathogenesis: the neural hypothesis reexamined. J Neurol Neurosurg Psychiatry 1984;47:437-42
26.
Lance JW. A concept of migraine and the search for the ideal headache drug. Headache 1990;30(suppl 1):17-23
27.
Kimura J. Electrodiagnosis in diseases of nerve and muscle: principles and practice, 2nd ed. 1989
28.
Kimura J. The blink reflex as a test for brainstem and higher central nervous system functions. In: Desmedt JE ed New developments in electromyography and clinical neurophysiology, vol 3. Basel: Karger, 1973:682-91
29.
Sanes JN, Foss JA, Ison JR. Conditions that affect the thresholds of the components of the eyeblink reflex in humans. J Neurol Neurosurg Psychiatry 1982;45:543-9
30.
Desmedt JE, Godaux E. Habituation of exteroceptive suppression and of exteroceptive reflexes in man as influenced by voluntary contraction. Brain Res 1976;106:21-9
