close

Вход

Забыли?

вход по аккаунту

?

Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potentials.

код для вставкиСкачать
Central Effects of Drugs Used
in Migaine Prophylaxis Evaluated
by Visual Evoked Potentials
Hans-Christoph Diener, MD, Erich Scholz, MD, Johannes Dichgans, MD, Wolf-Dieter Gerber, PhD,
Agnes Jack, Artur Bille, and Uwe Niederberger
The present study used recordings of visuai potentials evoked by pattern reversal (VEPs) to investigate the centrai
effects of three drugs used in migraine prophylaxis: the caicium channel blocker nifedipine, the beta-1-selective
blocker metoprolol, and the nonselective beta adrenoreceptor blocker propranolol. The study involved 58 patients
with common or classicai migraine who were treated in a double-blind randomized study over a period of 7 months,
while the effectiveness of prophylactic treatment was recorded in headache diaries that were subjected to time series
anaiysis. VEPs were recorded at the beginning of a 2-month baseline period without treatment, after 4 months of
treatment, and at the end of a 3-month washout period. At baseline, migraine patients had significantly higher VEP
amplitudes and longer latencies than did a group of 87 heaithy contro1 subjects. Patients were separated by statistical
analysis into responders and nonresponders to each prophylactic treatment. Nifedipine had no effects on the frequency, intensity, and duration of migraine attacks, nor on amplitude and latency of the VEPs. In contrast, the use of
beta blockers resulted in a significant decrease in VEP amplitude, both in responders and nonresponders, whereas VEP
latency remained unchanged. VEP amplitudes returned to the initiai values at follow-up in the nonresponders, but
stayed at lower levels in responders. Beta blockers thus appear to have a significant effect on the increased excitability
of the visuai system in patients with migraine, although their action is not directly related to their reduction of
migraine frequency.
Diener H-C, Schoiz E, Dichgans J, Gerber W-D, Jack A, Bille A, Niederberger U. Central effects of drugs
used in migraine prophylaxis evaluated by visual evoked potentials. Ann Neurol 1989;25:125-130
Evidence has accumulated during the last 10 years that
the primary pathogenetic mechanism in migraine is not
vascular but neurogenic, related to changes in neurotransmitter levels [i, 2). A purely vascular mechanism
could not explain abnormalities of the electroencephalogram (EEG) {3, 41,contingent negative variation 15,
61, and VEPs between migraine attacks (for a review
see Diener and colleagues ['I)).
VEP latencies measure
conduction velocities in the optic nerve and the centra1
optic pathways to the leve1 of the visual cortex, while
the amplitude of the VEP represents the number of
receptors stimuiated in the retina and the excitatility
of the visual correx. Several studies in the past have
found increased VEP ampiitudes in patients with migraine [7-111, which was interpreted as evidence for
the increased excitability of the occipital cortex in migraine.
In the present study, we investigated whether
prophylactic migraine treatment with beta blocking
agents or calcium channel blockers altered VEPs as
well as migraine frequency and intensity. If this were
the case, we wanted to see which functional subunits of
the visual system were affected. The checkerboard patterns used in ciinical practice provide the visual system
with luminance changes perceived in parafoveal and
peripheral retinal areas. This information is probably
transmitted by retinal ganglion cells responsive to
changes in luminance 112). As another approach,
stripe patterns with a very high spatial frequency (> 8
cyddeg, i.e., more than 8 black and 8 white stripes per
degree of the visual field) were used to test the channel
responsive to contours. This stimulus leads to longer
VEP latencies and decreased amplitudes compared
with the checkerboard pattern at a spatial frequency of
O. 5 cyc/deg [13).
Beta-adrenoreceptor antagonists as well as calcium
channel blockers have been shown to be effective in
treating migraine. Beta blockers might exert an effect
in the centrai nervous system (CNS), because betaadrenergic receptors can be found in the human cortex
1141, and propranolol, pindolol, and atenolol have
been shown to cross the blood-brain barrier [15].
From the Departments of Neurology and Neuropsychology, Universiry of Tuebingen, Tuebingen, Federal Republic of Germany.
Address correspondence to Dr Diener, Neurologische UniversitatsKlinik Kliniken Schnarrenberg, Hoppe-Seylerstr. 3, D-7400
Tuebingen 1, Federal Republic of Germany.
Received Apr 22, 1988, and in revised form Jul 15. Accepted for
publication Jul 16, 1988.
Copyright O 1989 by the American Neurologica1 Association
125
Table 1. Demographic and Clinica1 Data of Migraine Patients and N o m l Subjects
Migraine Patients
Characteristic
Propranolol
Metoprolol
Nifedipine
Number
Men
Women
Mean age (yr)
Common migraine
Classical migraine
Total duration of
migraine (yr)
Migraine attackdmonth
Migraine daydmonth
19
22
4
18
42.9
21
1
21
17
3
16
43.2
18
1
23
13
40.9
15
2
18
3.3
5.1
3.8
7.6
3.5
5.9
The present study compares the prophylactic effects
of a beta-1-selective blocker like metoprolol against a
nonselective blocker such as propranolol. Earlier studies indicated an equivalent therapeutic effectiveness
[lb, 171. If both substances are equaily effective, one
would prefer to use a beta-1-selective blocker to avoid
the side effects due to beta-2-blockade (bronchoconstriction, hypoglycemia). A recent survey indicated no
major differences in prophylactic efficacy between diltiazem, flunarizine, nifedipine, nimodipine, and verapamil [i@.We selected nifedipine as a calcium channel blocker.
Methods
Study Design
The study was performed double-blind over 12 months. In
the baseline period lasting for 2 months, patients were not
allowed to take any prophylactic migraine medication but
could take their abortive migraine attack medication. In
month 3, we applied 50% of the final dosage of either propranolol, metoprolol, or nifedipine. During the next 3
months, patients were either treated with 200 mg metoprolol, 160 mg propranolol, or 40 mg nifedipine per day.
Thereafter, dosages were reduced by 33% each month. The
follow-up period comprised another 3 months without
prophylactic treatment. Informed consent was obtained from
al1 patients.
Heuhche Evabation
Al1 patients kept diaries and recorded the occurrence, intensity, duration, and location of headache (migrainous or nonmigrainous), weight, and sleep duration and quality as well as
the number of analgesics or antimigraine drugs taken. Statistical analysis was based on time-series analysis in single patients and an analysis of variance for the comparison of subgroups of patients. Patients were considered responders to
migraine prophylaxis if they showed a significant decrease in
migraine frequency compared with the baseline period.
4
Total
Migraine
Patients
58
11
47
42.3
54
Contro1
Subjects
81
35
52
35.3
4
tion of Headache 1191. Patients were randomly assigned to
one of the three treatment groups. Stratifying factors were
age, gender, and migraine characteristics such as duration and
frequency of migraine attacks. Exclusion criteria were:
asthma, cardiac disorders, diabetes mellitus, any neurological
disorder, pregnancy, and habitual intake of analgesics on
more than 15 days a month. The contro1 population consisted of 87 healthy subjects without headache who were not
taking medication. Demographic and clinical data are shown
in Table 1.
Visuul Evoked Potentials (VEPs)
VEPs were recorded three times, the first at the beginning of
the baseline phase, the second at the end of the high-dosage
period, and the third at the end of follow-up. The recordings
took place in a darkened room. Stimulus patterns were presented on a video screen subtending 12 x 15 degrees of
visual angle with a pattern contrast of 99%. We used three
different stimulus patterns and two temporal frequencies of
pattern reversal. The checkerboard pattern contained blackand-white, 1 x 1 degree squares. For transient stimulation,
we applied a repetition frequency of 1.56 Hz, for steadystate stimulation, 8.33 Hz. The stripe patterns contained vertical black-and-white stripes with a spatial frequency of 3 cyd
deg (iarge stripes) or 9 cyc/deg (narrow stripes). The
stimulation was transient (1.56 Hz) again. Surface gold electrodes were attached to the head in the midline 2.5 cm above
the inion and at the left ear lobe. Subjects were instructed to
fixate a red light diode 3 cm below the upper end of the
screen. Stimulation was performed monocularly. Prior to the
recording, we measured visual acuity and applied correcting
glasses if necessary. EEG signals were amplified, filtered, and
averaged across 64 trials.
VEPs were evaluated in terms of latency and amplitude of
P 100 at the end of che study. The amplitude was measured
as A = (N1 - P l ) + (N2 - P1)/2. The person who
measured latencies and amplitudes was unfamiliar with the
aim of the study.
Statistica[ Evabation
Popuiation
We included 58 patients with migraine, diagnosed according
to the criteria set by the Ad Hoc Committee on Classifica-
126 Annals of Neurology
VOI 25 N o 2
February 1989
Migraine patients were classified into responders and nonresponders based on time-series analysis from baseline and
treatment periods. In addition, we applied tests for related
Table 2. Comparison of VEP Amplitudes and Lutencies
Between Patients with Migraine and Contro1Subjects
2 30[
I***
Y
Stimulus
Population
Mean
Significance
I***
I.**
VEP AMPLITUDE (JLV)
Checkerboard
Transient
Steady state
Stripes
Large
Narrow
N
M
N
M
14.6 i
18.8 k
14.8 i
17.8 +-
8.6
6.8
6.3
8.1
p < 0.001
N
M
N
M
14.0 i
17.5 +7.8 f
6.8 k
7.8
7.4
5.3
3.8
p < 0.001
5.0
5.7
6.5
10.4
p < 0.001
M
109.6 i
112.3 k
113.2 i
117.9 i
N
M
N
M
115.2 f
117.6 k
121.1 i
139.0 f
6.4
5.4
9.0
9.7
p < 0.001
Y
p < 0.001
2w
p < 0.001
CH
NS
VEP LATENCY (MS)
Checkerboard
Transient
N
M
Steady state
Stripes
Large
Narrow
N
VEP = visual evoked potential; M
jects; NS = not significant.
=
migraine; N
.,
STST
LS
NS
Fig I . Mean vabes and standard deviations of visual evoked
potential (VEP) amplitudes from norma1 subjects (black columns) and patients with migraine (hatched columns). CH =
transient checkerboard stimulation;STST = steady-state
checkerboard stimulation; LS = stripe pattern with lmu spatial
frequenq; NS = stripe pattern with high spatial frequency.
Asterisks indicate significant diffences between the two groups.
p < 0.001
r
%
'"I
I
140
I***
I-
=
control sub-
a
-I
n
w
120
>
and unrelated samples, a one-way analysis of variance to
compare responders and nonresponders, and a two-way analysis of variance covering the effects of prophylaxis and the
three VEP measurements. Levels of significance were fixed
a t p < 0.01 a n d p < 0.001.
Resuits
VEPs in Normal Subjects and Patients with Migraine
We first compared VEP amplitudes and latencies for
ail stimulation modes and populations between the
right and left eye. Because t tests revealed no significant difference between the two eyes, we subsequently
calculated mean values from both eyes for each subject
(Table 2). In patients with migraine, compared to control subjects, amplitudes were larger (Fig 1) and latencies were increased (Fig 2), with the exception of the
VEP from the stripe pattern with a high spatial frequency. VEP amplitudes were comparable for transient checkerboard and large stripe pattern as well as
steady-state checkerboard stimulation, but reached
only about 50% with the narrow stripe pattern. This
drop in amplitude was due to the high spatial frequency at the threshold of optical resolution. Increasing spatial frequencies of stimulus patterns is known to
result in longer VEP latencies { 131. Correspondingly,
VEP latencies increased by 5 to 6 ms from transient
checkerboard stimulation (spatial frequency = 0.5 cyci
deg) to large stripes (spatiai frequency = 3 cycldeg)
1O 0
CH
STST
LS
NS
Fig 2. Arithmetic means and standard deviations of visual
evoked potential (VEP) kztencies in norma1subjects and patients
with migraine. Abbreviations are the same as in Figure I .
and again to narrow stripes (9 cyddeg). Steady-state
stimulation resulted in a phase shift of the VEP, leading to a latency shift of about 4 to 5 ms compared with
transient stimulation 1201.
VEPs During Migraine Prophykzxis
Statistical analysis revealed that 12 of 22 patients
treated with metoprolol and 6 of 19 patients treated
with propranolol, but only 1 of 17 patients treated
with nifedipine, benefited from medication in terms of
migraine frequency reduction. Consequently, of the
two patient groups treated with beta-blocking agents,
18 were classified as responders and 23 as nonresponders. Both groups were comparable in terms of age,
sex distribution, and migraine characteristics. We did
not further separate patients into those taking propran0101 and those taking metoprolol because the resulting
numbers would have been too small for a reliable statistical analysis. The 16 patients who did not respond
to nifedipine were used as a control group for the
repeated VEP testings.
Diener et al: Migraine Prophylaxis and VEPs
127
Table 3. Summary of Statistica1 Analysis of Changes
in VEP Amplitude: Comparison between daseline,
High-Dosage, and Follow-up
Stimulation
TRANSIENT CHECKERBOARD
Group
BL-HD
BL-FU
Responder
Nonresponder
Nifedipine
Responder
Nonresponder
Nifedipine
#
#
#
NS
NS
NS
#
#
#
NS
NS
NS
Responder
Nonresponder
Nifedipine
Responder
Nonresponder
Nifedipine
#
#
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
~~
Checkerboard
Transient
Steady-state
Stripes
kge
Narrow
BL
HD
FU
Fig 3. Artthmetic meuns of &sual evokedpotential (VEP) amplitudes after transient checkerboard stimulation at baseline
(BL), high dosage (HD), andfollow-up (FU) in patients that
responded to beta blocking therapy (RESP), in patients that did
not respond t o beta blockers (NON),and in patients receiving
nifdipine (NIF).
*Significant decreases in VEP amplitude ( p < 0.01).
VEP
FU
= visual evoked potential; BL = baseline; HD =
= follow-up; NS = not significant.
high dosage;
Table 4. Means and Standard Dwiations (SO)
of VEP Amplitude (p.V) Before, During, and
After Migraine Prophylaxisa
Baseline
Responder (18)
Mean
SD
Nonresponder (23)
Mean
SD
Nifedipine ( 16)
Mean
SD
High-dose
z
120
W
I-
5
Follow-up
110
n
w
18.8
6.5
16.2
4.8
>
15.6
5.1
100
BL
HD
FU
~~
17.6
9.0
15.4
5.9
16.7
7.6
15.9
6.6
15.1
5.4
14.8
6.2
"Steady-state stimulation.
VEP amplitudes and latencies were not significantly
different between those who responded to beta blockers and those who did not, and those who took
nifedipine at baseline recording. The responders exhibited a significant decrease in VEP amplitude (between 14 to 19% of original amplitude; -3-4 pV)
both in high dosage and follow-up compared with
baseline (Tables 3, 4; Fig 3). With high spatial frequency testing, however, this effect could not be seen.
The amplitude effect of beta blocking agents was not
directly related to the therapeutic effectiveness, because nonresponders also showed a significant decrease in VEP amplitude during treatment. The VEP
amplitudes of nonresponders returned to initial levels
at follow-up, whereas VEP amplitudes of responders
remained reduced. VEP amplitudes remained unchanged throughout the treatment in the nifedipine
group.
i28 Annais of Neurology VOI 25 No 2 February 1989
F i g 4. Mean values and standard deviations of visual evoked
potential (VEP) latencies during stimulation with the stripe pattem with low spatial frequency at baseline (BL), high dosage
(HD), a n d f o l h - u p (FU). Valuesfrom responders and nonresponders to beta blocking agents are depicted as black and white
columns, respectively. Tbe shaded columns sbmu the mean values.
VEP latencies were unchanged in al1 groups of patients for the duration of the study (Fig 4). Only 1 of
36 comparisons (3 groups of patients x 3 VEP recordings x 4 stimuli) showed a significant shortening of
VEP latency, attributable to chance variation.
To summarize, we found a significant decrease in
VEP amplitude in migraine patients treated with betablocking agents, although this effect was not related to
the effectiveness of the drug in migraine prophylaxis.
The amplitude decrease could be observed only in
VEPs, where the criticai factor is luminance change,
but not in patterns that preferentially are evoked
through foveal vision.
Injuence of Migraine Abortive Medication
To investigate the possible effects of centrally acting
components of antimigraine drugs on the VEP, we
carefully checked the diaries and found 16 occasions
when the VEPs were recorded within a 48-hour period
following an acute migraine attack, when the patient
had taken caffeine, ergotamine, barbiturates, codeine,
or a combination of these. For comparison, we randomly selected 16 VEP recordings that were taken
within the same patient population and at comparable
times of treatment, but without medication; t tests for
unrelated samples failed to show any differences in
terms of VEP latency or amplitude between the two
groups. The earlier observed changes in VEP amplitudes therefore cannot be explained by the intake of
abortive medication.
Discussion
The present study found significantly increased amplitudes of VEPs in patients suffering from migraine
compared with normal control subjects. In an earlier
study involving a different population of migraine patients (n = 190), we also observed a 20 to 30% increase in VEP amplitude compared to that of normal
subjects 171. Even in periods between attacks, patients
with migraine thus exhibited a higher retinal or cortical
excitability. This view is supported by the observation
that amplitudes of the contingent negative variation
(CNV), an event-related slow cerebral potential, are
increased in migraine patients compared with control
subjects [b}.The difference has been attributed to centrai catecholaminergic hyperactivity 151. Increased central noradrenergic activity is believed to be one of the
basic mechanisms in migraine pathogenesis [2 1, 221.
The increased VEP amplitudes could only be seen
when parafoveal and peripheral retinal areas were
stimulated through luminance changes, but not with
stimuli that were preferentially transmitted through
foveal vision. This finding corresponds with the clinical observation that patients with common migraine
complain about intensified light perception (photophobia). Visuai channels carrying information concerning luminance and contrast perception with fine
grating therefore seem to be differentially affected in
migraine.
The observed increase in latency of P 100 in patients with migraine compared with normal subjects is
difficult to explain. Morphological changes in the optic
nerves and the central pathways can be excluded. Recent studies in patients with Parkinson’s disease prior
to and during treatment with L-dopa showed significant
VEP latency changes, indicating that changes in neurotransmitter contents in the retina and the central nervous system can influence VEP latencies [23}.
The latency changes cannot be explained by the relatively larger number of women in the migraine group
because women, due to their smaller head circumference and higher basal temperature, exhibit shorter
VEP latencies than men. Although VEP latencies increase linearly with age, the difference in mean age of
7 years between patients and control subjects is not
enough to explain the latency difference.
Beta-blocking agents given for migraine prophylaxis
restored the increased VEP amplitudes to a leve1 corresponding to that of a normal population, but the
calcium antagonist nifedipine had no such effect.
Nyrke and colleagues [il} were able to show that
treatment with propranolol significantly reduced VEP
amplitudes in patients with migraine, and Schoenen
and coworkers [51 observed a normaiization of the
increased CNV amplitude with metoprolol. The decrease in VEP amplitude was correlated with clinical
effectiveness of metoprolol in the prevention of migraine attacks. The calcium channel blocker flunarizine, although clinically effective, did not alter CNV
amplitudes 151.
In contrast to the study of Schoenen {SI, we found
no correlation between decrease of VEP amplitude
and clinical effects of beta blockers. Stimulation of the
brainstem reticular formation in the cat resulted in
facilitated late cortical components of the VEP 1241. A
number of pharmacological substances known to be
effective in human migraine prophylaxis, including
propranolol, had no significant effects on reticular formation-induced facilitation of VEPs 1241.
Both responders and nonresponders to migraine
prophylaxis showed a similar decline of VEP amplitudes. In responders, however, the lower VEP amplitudes could still be observed 3 months after the end of
treatment. We first ascribed this phenomenon to the
long-lasting effect of migraine prophylaxis with beta
blockers 1251. The headache diaries, however, clearly
showed that migraine frequency had returned to the
baseline value at the end of the follow-up period (for
details see Scholz and associates [26].
A placebo effect was ruled out by the results of the
nifedipine group. Influences caused by the migraine
attack medication were also shown to be negligible.
VEP amplitudes after stimulation with stripe patterns
of high spatial frequency were normal in patients with
migraine and did not change with treatment. This is
another argument fora selective action of beta blockers
on luminance-dependent subunits of the visual system.
A possible explanation for the discrepancy between
clinical effectiveness and influence on the VEP is provided through the measurements of drug plasma
levels. The study of Scholz and colleagues (unpublished data) showed significantly lower plasma levels of
metoprolol in nonresponders. These plasma levels
were obviously high enough to exert action on the
visual system but still too low to affect the frequency
of migraine recurrence. The electrophysiological
changes described here are group effects. It is therefore not possible to predict the possible effectiveness
of beta blockers as migraine prophylaxis on the basis of
VEP amplitude.
Diener et
ai:
Migraine Prophylaxis and VEPs
129
Finally, we would like to reemphasize that the increased VEP amplitude in patients with migraine, the
decrease in VEP amplitudes caused by beta blockers in
migraine patients, and the discordance between clinicai
effects and VEP amplitude can ai1 be explained on the
basis of a purely retinai effect or a purely corticai effect
or a combination of the two.
We thank Dr J. W. Lance for critical comments, and B. Gross, C.
Portzehl, and B. Guschlbauer for technical assistance.
References
1. Lance JW.
The pathogenesis of migraine. In: Lance JW, ed.
Mechanisms and management of headache. London: Butterworth, 19821102-120
2. Olesen J. The pathophysiology of migraine. In: Clifford Rose F,
ed. Handbook of clinical neurology. Amsterdam: Elsevier,
1986~59-83
3. Hockaday JM, Whitty, CWM. Factors determining the electroencephalogram in migraine: a study of 560 patients, according
to clinical type of migraine. Brain 1969;92:769-788
4. Wessely P, Mayr N, Goldenberg G. EEG-Befunde bei komplizierter Migrane. Z EEG-EMG 1985;16:221-226
5. Schoenen J. Sympathetic hyperarousal in migraine? Evaluation
by contingent negative variation and psychomotor testing: effects of beta-blockers. In: Clifford Rose F, ed. Advances in
headache research. London: John Libbey & Co, 1987:155-160
6. Schoenen J, Maertens A, Timsit-Berthier M, Timsit M. Contingent negative variation (CNV) as a diagnostic and physiopathologic tool in headache patients. In: Clifford Rose F, ed.
Migraine. Proceedings of the Fifth International Migraine Symposium, London, 1984. Base1 Karger, 1985:17-25
7. Diener HC, Ndosi NK, Koletzki E, Langohr HD. Visual
evoked potentials in migraine. In: Pfaffenrath V, Lundberg PJ,
Sjaastad O, eds. Updating in headache. Berlin: Springer Verlag,
1984:lOl-106
8. Connolly JF, Gawel M, Rose FC. Migraine patients exhibit abnormalities in the visual evoked potential. J Neurol Neurosurg
Psychiatry 1982;45:464-467
9. Kennard C, Gawel M, Rudolph N, Clifford Rose F. Visual
evoked potentials in migraine subjects. Res Clin Stud Headache
1978;6:73-80
10. Lehtonen JB. Visual evoked cortical potentials for single flashes
and flickering light in migraine. Headache 1974;14:1-12
11. Nyrke T, Kangasniemi P, Lang AH, Petersen E. Steady-state
130 Annals of Neurology VOI 25 No 2 February i989
visual evoked potentials during migraine prophylaxis by propranolol and femoxetine. Acta Neurol Scand 1984;69:9-14
12. Kandel ER. Processing of form and movement in the visual
system. In: Kandel ER, Schwartz JH, eds. Principles of neural
science, ed. 2 New York: Elsevier, 1985:366-383
13. Stohr M, Dichgans J, Diener HC, Buettner UW. Evozierte
Potentiale. Berlin: Springer Verlag, 1982
14. Reznikoff GA, Manaker S, Rhodes CH, et al. Localization and
quantification of betaadrenergic receptors in human brain. Neurology 1986;36:1067- 1073
15. Taylor, EA, Jefferson D, Carroll JD, Turner P. Cerebral spinal
fluid concentrations of propranolol, pindolol, and atenolol in
man: evidence for centrai action of beta-adrenoreceptor antagonists. Br J Clin Pharmacol 1981;12:549-559
16. Kangasniemi P, Hedman C. Metoprolol and propranolol in the
prophylactic treaunent of classical and common migraine: a double blind study. Cephalalgia 1984;4:91-96
17. Olsson JE, Behring HC, Forssman B, et al. Metoprolol and
propranolol in migraine prophylaxis: a doubie-blind multicenter
study. Acta Neurol Scand 1984;70:160-168
18. Solomon GD. Comparative efficacy of calcium antagonist drugs
in the prophylaxis of migraine. Headache 1985;25:368-371
19. Ad Hoc Committee on Classification of Headache: Classification of headache. Arch Neurol 1962;6:173-176
20. Diener HC, Zimmermann C. Visuell evozierte Potentiale:
methodische Probleme-Variation der Reizparameter. Z EEGEMG 1985;16:155-1 57
2 1. Anthony M. The biochemistry of migraine. In: Clifford Rose F,
ed. Handbook of clinical neurology. Amsterdam: Elsevier,
1986:85-105
22. Lance JW,Lambert GA, Goadsby PJ, Duckworth JW.
Brainstem influences on the cephalic circulation: experimental data
from cat and monkey of relevance to mechanism of migraine.
Headache 1983;23:258-265
23. Bodis-Wollner J, Yahr MD. Measurements of visual evoked
potentials in Parkinson’s disease. Brain 1978;101:661-671
24. Adams RW, Lambert GA, Lance JW. Brainstem facilitation
of visual evoked response in the cat. Source, pathway, and role
of nicotine receptors. Electroencephalogr Clin Neurophysiol
1988;69:45-54
25. Diamond S, Kudrow L, Stevens J, Shapiro DB. Long-term study
of propranolol in the treatment of migraine. Headache
1982;22:268-271
26. Scholz E, Gerber WD,Diener HC, et al. Dihydroergotamine vs
flunarizine vs nifedipine vs metoprolol vs propranolol in migraine prophylaxis: a comparative study based on time series
analysis. In Clifford Rose F, ed. Current problems in neurology:
4. London: John Libbey & Co, 1987:139-146
Документ
Категория
Без категории
Просмотров
0
Размер файла
592 Кб
Теги
visual, potential, prophylaxis, central, effect, drug, migraine, evaluate, used, evoked
1/--страниц
Пожаловаться на содержимое документа