-
Journal of Neurology, Neurosurgery, and Psychiatry 1985;48:
1277-1283
Dopamine agonists suppress visual-cortical reflexmyoclonusJA
OBESO, J ARTIEDA, T TUNON,* MR LUQUIN, JM MARTINEZ LAGEFrom the
Movement Disorders Unit, Department ofNeurology, Clinica
Universitaria, University ofNavarra,Pamplona, Spain.
SUMMARY Two patients with a diagnosis of olivo-ponto-cerebellar
atrophy developed corticalreflex myoclonus to visual (flash) and
somaesthetic stimuli. Oral treatment with levodopa-carbidopa
(1000/100 mg) or subcutaneous administration of apomorphine (1 mg)
abolished thevisually-triggered myoclonus, without modifiying
reflex myoclonus to electrical or tactile stimula-tion. Intravenous
administration of lisuride (0-1 mg) produced a marked reduction in
both typesof reflex myoclonus. These results indicate a selective
inhibitory effect of dopamine agonist drugson visual reflex
myoclonus of cortical origin.
In recent years the pharmacological basis of myo-clonus has been
focused on a disorder of cerebralserotoninergic mechanisms. This
followed the dis-covery by Lhermitte et al,' 2 later confirmed
byothers,36 that oral treatment with5-hydroxytryptophan (5-HTP)
plus carbidopa pro-duced a reduction in post-anoxic action
myoclonus,and the findings of low CSF levels of5-hydroxyindolacetic
acid in similar patients whoresponded to treatment with 5-HTP
orclonazepam.78 However, a deficit of serotonin maynot be important
in other myoclonic disorders9 10 inwhich other neurotransmitters
may be involved. Theanti-myoclonic effect of clonazepam, valproic
acidor primidone might be due at least partially, toenchancement of
cerebral gamma aminobutyric acid(GABA) activity." A protective
effect of apomor-phine against visually induced myoclonus has
beendemonstrated in the baboon.'2 Quesney et al'3 foundthat in
patients with generalised epilepsy, apomor-phine produced transient
inhibition of spike andwave EEG activity induced by photic
stimulation,suggesting a dopamine influence on certain types
ofmyoclonus.
Cortical reflex myoclonus results from abnormal
*Present address: Neuropathology section, Hospital de
Navarra,Pamplona.
Address for reprint requests: Dr JA Obeso, Neurologia,
ClinicaUniversitaria, Apartado 192, Pamplona, Spain.
Received 23 January 1985 and in revised form 9 May 1985.Accepted
17 May 1985
motor cortex activity triggered by sensory input.'4
'5Electrophysiological characteristics of cortical myo-clonus are
the presence of enhanced cortical evokedpotentials, EEG activity
time-locked to the musclejerks and brief EMG discharges.4 12
Clinical andelectrophysiological studies indicate the existence
ofseparate mechanisms underlying different types ofcortical
myoclonus in man.'6 Such pathophysiologi-cal discrimination may
also indicate different phar-macological characteristics. For
example, corticalreflex myoclonus to somaesthetic stimulation
ishighly responsive to serotonin agonists, but is notimproved by
dopaminergic drugs.'7 We now report aselective effect of
levodopa-carbidopa and apomor-phine on cortical reflex myoclonus
induced by photicstimulation in two patients with
olivo-ponto-cerebellar-atrophy. These two cases were includedin a
previous report on the pathophysiology of corti-cal
myoclonus.'6
Method
Electrophysiological technique A Medelec MS 6 machinewas used
for electrophysiological investigations.Somatosensory evoked
potentials (SEPs) to digital nervestimulation were recorded from a
scalp electrode placed onthe hand area (7 cm lateral and 2 cm
posterior to thevertex) with the reference electrode on Fz (10-20
EEGinternational system). Visual evoked potentials (VEPs) toflash
stimulation recorded from the scalp over the occipitalcortex also
were recorded. For reasons explained previ-ously,'8 we have
designated the major cortical potentialpeaks by their polarity and
sequence (Ni, P1, N2, etc).The electromyographic (EMG) reflex
responses elicited byelectrical or flash stimulation were recorded
simultane-
1277
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x
Fig 1 Case 1. Transverse sections of the cerebellum, ponsand
medulla. Cerebellar white matter is considerablyreduced in volume;
both dentate nuclei appear normalmacroscopically. There is severe
atrophy ofthe pons andmiddle cerebellar penduncles (single arrow).
The brachiumconjuctivum is normal bilaterally. In the medulla the
normalprotusion ofthe inferior olive has disappeared
(doublearrow).
ously by surface electrodes placed on biceps brachii orfinger
flexors. The amplitude of the reflex EMG dischargeswas measured as
the maximum interpeak value on averagerecords before and after each
pharmacological test. Theduration of the EMG bursts usually
remained constantthroughout each session.
Case reportsCase 1 M. R. (Clinica Universitaria No 136647)A
65-year-old woman with a history of unsteadinessof gait beginning
in 1978 was investigated in 1979for a cerebellar syndrome, but no
cause was found.There was no family history of neurological
disease.By 1982 the patient had lost facial expression,
haddifficulty in performing normal daily motor tasksand had
frequent falls. She was also incontinent ofurine and could not
swallow solid food. Examinationshowed marked rigidity and akinesia
as well as dys-metria of the limbs. She could not stand or
walkalone. Pursuit eye movements were interrupted andthere were
ocular dysmetria and "square wave"jerks. Mentation was intact.
Cranial nerves, tendonjerks and sensation were all normal. There
was noorthostatic hypotension. Brief light touch or pin-prick of
the skin area innervated by the medial plan-tar nerve of either
foot provoked repetitive jerkingof the toes lasting up to 1 second.
When the stimuluswas applied to the great-toe, or to the second toe
oradjacent area, the jerk consisted of extension of thegreat toe
and flexion of the other toes. There was novisible muscle jerking
when the patient voluntarilymoved the foot or toes. A few months
later, whenher general condition had deteriorated, it wasnoticed
that touch and particularly pin-prick to the
Obeso, Artieda, Tufz6n, Luquin, Lage
dorsal region of the thumb or forefinger producedbrief and
repetitive jerks of the forearm and bicepmuscles. A CT scan
revealed severe brainstem andcerebellar atophy, but the cerebral
hemisphereswere normal. The clinical diagnosis of
sporadicolivo-ponto-cerebellar atrophy was made. In Janu-ary 1984
EEG showed diffuse theta rhythm at rest,but flash stimulation
provoked generalised musclejerking which blurred the EEG trace,
without loss ofconsciousness. The patient was treated
withlevodopa-carbidopa ( 1000/100 mg/day), bromocrip-tine (30
mg/day), lisuride (5 mg/day) and thyroxinereleasing hormone (TRH)
iv (10 mg/day) with noimprovement in her akinesia and ridigity. She
diedof pneumonia in March 1984.On post-mortem examination the brain
weighed
1180 g. The brainstem and cerebellum weighed120 g (normal
control values 160 + 10 g). Macros-copic examination after fixation
showed severeatrophy of the pons, inferior and middle
cerebellarpeduncles and cerebellum (fig 1). The substantianigra and
locus coeruleus appeared mildly depig-mented. The putamen was
shrunken bilaterally andthe cerebral hemispheres were normal. The
spinalcord was normal macroscopically. For histologicalstudies, the
whole cerebellum, blocks of severalother brain regions and the
spinal cord were embed-ded in paraffin wax. Sections were stained
withhaematoxylin-eosin, luxol fast-blue, Bielchowsky,Nissl, Holsen
and Spilmeyer.Microscopic examination of the pre-trontal,
sensory-motor and visual cortex did not reveal anyhistological
abnormality (fig 2A). Neuronal loss andfibrillary gliosis were very
severe in the putamen(fig 2B) and moderate in the external globus
pal-lidus. The internal globus pallidus, caudate,thalamus,
subthalamus, hypothlamus, red nucleusand geniculate bodies were
normal. In the mesence-phalon (fig 2C), the substantia nigra (pars
reticulataand compacta) and locus coeruleus showed intensegliosis
and 20% decrease of pigmented neurons.Lewy bodies and
neurofibrillary tangles were notpresent. The superior cerebral
peduncle was normal.In the pons, neuronal loss and gliosis was
wide-spread and very severe (fig 2-D), sparing only partof the
raphe nuclei. The middle and inferior cerebel-lar peduncles were
thin and severely demyelinated.The arcuate fibres also were
damaged. The cortico-spinal tract was slightly pale, but the medial
lon-gitudinal fascicle and the central tegmental tractwere normal.
In the cerebellum (fig 2E) the whitematter was severely
demyelinated. Purkinje cellswere markedly reduced in number and
there wasBergmann glia proliferation. The molecular layershowed
moderate gliosis; the granular layer wasslightly thinner than
normal. Within this latter layer,
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Dopamine agonists suppress visual-cortical reflex myoclonus
K)
U~~ ~~vtesw.pu A
s, V a
St * ta/SSt SwfIN~~~~~~~~~~~~$
';.A
/'
swei ^ 9 _ Sr ^. - t > lib Ee- q-
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Fig 2 Case 1. Microscopic sections at different levels ofthe
brain. (A) Cortex. Normal somatosensory cortex. One bar =650 pum.
(B) Putamen. Intense gliosis and marked neuronal loss. Holzer
stain, One bar = 650 pm. (C) Substantia nigra.Severe fibrillary
gliosis. Surviving neurons are normaL Hoizer stain, One bar = 500
pim. (D) Pons. Transverse myelinatedfibres are considerably reduced
(upper half); abundant fibriUlary gliosis. Vertical fibres
arepreserved (asterisk). Hoizer stain.One bar = 710 pum. (E)
Cerebellum. Intense demyelination (arrow). The dentate nucleus and
its ribbon are normal. Luxolfast blue. One bar = 1600 pm. (F)
Medulla. Striking neuronal loss and fibrillary gliosis ofthe
inferior olive. Holzer stain.One bar = 710 pm.
i( d') *
1279
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..
;1 t. .;
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Apomorphine4 4 4 -4 4 4 4 4VEA
I1_ _
0D
----V"-vA
EMG
500 ms
SEP
EMG
200msFig 3 Case 1. Visual evoked potentials (VEP) to
flashstimulation (arrows) at a frequency of10 Hz,somatosensory
evoked potentials (SEP) to digital nervestimulation ofthe right
forefinger and electromyographic(EMG) recording of the reflex jerks
from right finger flexormuscles. Each trace is the average of32
responses. (A) and(C) control records. (B) and (D) after 1 mg
ofsubcutaneousapomorphine. Reflex myoclonus to flash stimulation
wasabolished by apomorphine, but electrically elicitedmyoclonus was
not decreased. Notice that the amplitude ofthe primary complex of
the VEPs remains constant. Thebaseline ofthe cortical record
changed slightly afterapomorphine; this variation was probably due
to theabsence ofmuscle artefact once the reflex myoclonus
haddisappeared. Vertical calibration bars are 50 ,uV for VEPs,25
,uV for SEP and 200 ,uV for EMG potentials.
axonal swelling (" torpedoes") from Purkinje cellswere observed.
The dentate nucleus and its ribbonas well as the other deep
cerebellar nuclei were pre-served. At the level of the medulla (fig
2-F) relevantabnormalities comprised severe neuronal loss
andfibrillary gliosis of the inferior olives and arciformnucleus,
the dorsal motor nucleus of the vagus, andthe hypoglosal nucleus.
Moderate demyelination ofthe spino-cerebellar tracts was present.
The spinalcord sections showed marked neuronal loss andgliosis of
the anterior and lateral horns with mildgliosis of Clarke's
columns.
Pharmacological and physiological studies1 Control Flash
stimulation at a frequency of 10to 20 Hz elicited rhythmical
myoclonus. At thesefrequencies each flash produced a large VEP
(50,uV) followed by a generalised jerk which caused anartifact in
the scalp (occipital) electrode (fig 3A).
Obeso, Artieda, Tunion, Luquin, LageThe latency of the first
positive peak of the VEP was32 ms and the time interval between
this peak andthe onset of the reflex EMG discharge recordedfrom
biceps brachii was 28 ms. SEPs were alsoenlarged (35 ,uV, P1-N2)
and were followed by areflex EMG discharge with a latency of 40 ms
afterthe stimulus recorded from biceps brachii (fig 3C).2
Apomorphine A single subcutaneous dose of1 mg of apomorphine was
given prior to intravenousadministration of 40 mg of domperidone.
Clinicaland electrophysiological evaluation of myoclonuswas
repeated 30 minutes after apomorphine. Themyoclonic jerking
previously provoked by flashstimulation at a frequency of 10 to 20
Hz wasabolished following apomorphine, but the amplitudeand
morphology of the primary complex of the VEPremained constant (fig
3B). The slight change inmorphology of the cortical record was
probably dueto the absence of muscle artefact. On this occasionthe
flash could be kept on indefinitely without elicit-ing any reflex
myoclonus. In contrast, the amplitudeof the EMG myoclonic discharge
produced by elec-trical stimulation of the fingers was not modified
byapomorphine (fig 3D).
3 Lisuride A single intravenous dose of 0-1 mgof lisuride was
given on a different day. Twentyminutes later, a striking reduction
in visual reflexmyoclonus was observed. However,
rhythmicaleye-blinking at the flash frequency was still
present.Reflex myoclonic jerking following touch or pin-prick was
decreased and the size of the EMG reflexdischarge elicited by
electrical stimulation wasdiminished to half of the control
value.
Case 2. PRL (Clinica Universitaria, No 73247).This 67-year-old
lady was diagnosed as having Par-kinson's disease in 1971. She
responded initially tolevodopa therapy and levodopa plus
benserazidesubsequently. In 1975, akinesia and rigidity hadbecome
prominent and a "wearing off phenomenon"was present. Bromocriptine
and amantadine wereadded but did not produce any greater
improve-ment. When examined in 1983, she was unable tospeak,
required assistance to walk a few metres andwas severely rigid.
There was also marked dys-phagia. Tendon jerks were exaggerated and
a rightBabinski sign was present. Pursuit ocular move-ments were
abnormal (cogwheeling) and oculardysmetria was observed upon
attempted saccadicmovements of the eyes. Dysmetria of the
upperlimbs in the finger-to-nose test was noticed, evalua-tion of
coordination in the lower limbs was madedifficult by severe
akinesia. Light touch or pin-prickto the fingers and toes, or
tapping the wrist or toeswith a tendon hammer, provoked repetitive
musclejerks localised to the stimulated limb. In the arm
1280
0 Control
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Dopamine agonists suppress visual-cortical reflex myoclonus
-_-Fig 4 CT brain scan ofpatient No 2. Marked brainstemand
cerebellar atrophy, the latter mainly due to atrophy ofthe vermis,
is observed (A and B). There is also slightdilatation ofthe third
ventricle and anterior horns (C),without cortical atrophy (D).
these were characterised by flexion of fingers, wristand elbow;
in the legs by flexion of the toes, andflexion/extension of the
great toe. Treatment withlevodopa-carbidopa was discontinued for a
few dayswith only slight deterioration in her motor capacity.At
this time, the flashing stimulus employed forroutine EEG recording
elicited repetitive general-ised myoclonic jerking unaccompanied by
loss ofconciousness. The CT scan showed mark atrophy ofthe
brainstem and cerebellar vermis with only mod-erate cortical
atrophy (fig 4). A clinical diagnosis ofsporadic
olivo-ponto-cerebellar atrophy was made.
ms later by a generalised jerk. SEPs were alsoincreased in
amplitude 25 ,uV (P1-N2) and wereassociated with reflex EMG
discharges occurringwith a latency of 40 ms in finger flexors.
2 On levodopa therapy The electrophysiologi-cal studies were
repeated three days after Sinemet275 (levodopa 250 mg, carbidopa 25
mg) (4tablets/day) had been restarted. At that time, flash-ing at
any frequency (3 to 50 Hz) during a prolongedperiod of time (up to
30 seconds) failed to elicit anyreflex myoclonus. However VEPs were
still enlarged(fig SB). Reflex myoclonic jerking triggered by
elec-trical stimulation was unchanged.
3 Lisuride 0 15 mg of lisuride was given IVwhen the patient was
taking her usual dose ofSinemet. Accordingly only the effect of
lisuride onsomaesthetically induced myoclonus could bestudied. A
marked reduction (90%) in the amp-litude of the EMG reflex
discharges recorded infinger flexors following digital nerve
stimulation wasfound, which corresponded with diminution in
reflexmyoclonus in the limbs observed clinically.
® Off-L-dopa
VEP
EMG® On-L-dopa
500 ms
She was treated with lisuride (3 mg/day p.o.) and Fig 5 Case 2.
(A) Visual evoked potentials (VEPs) andlevodopa-carbidopa 275 (4
tablets/day p.o.) without reflex EMG discharges recorded from right
biceps brachii tofurther improvement. A few months later she died
flash stimulation (arrows) at a frequency of6 Hz, while theof
aspiration pneumonia at home. patient was not receiving any
dopamine agonist. (B)
Following oral treatment with levodopa-carbidopaPharmacological
and physiological studies (1000/100 mglday). The reflex muscle
responses were1 Off levodopa therapy. Flash stimulation at a
abolished after levodopa without change in the amplitude ofthe
VEPs. The late positive wave observed in the controlfrequency of 3
Hz (or greater) induced generalised VEP represented a muscle
artefact due to the reflexand rhythmical myoclonus (fig SA). Each
flash pro- myoclonus; accordingly it is not present after
treatment.duced a large VEP (50 gV) which was followed 30 Vertical
bar is SO uV for VEP and 500 ,uV for EMG trace.
1281
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Discussion
Dopamine agonists abolished cortical reflex myoc-lonus to flash
stimulation in two patients witholivo-ponto-cerebellar atrophy.
These results ex-tend the findings of Quesney et al'3 1'
ofapomorphine-induced suppression of photosensitiveepileptic
discharges in humans, and support experi-mental work indicating a
strong inhibitory action ofdopamine agonists upon the
photomyoclonicresponse in the baboon Papio papio.'2 The site
andmechanism of action of dopamine agonist inhibitionof the
abnormal cortical discharges producing myo-clonus is not clear.
Dopamine agonists did notreduce the amplitude of the VEPs preceding
themyoclonic jerks in either of the two patients, indicat-ing that
the antimyoclonic effect of these drugs wasnot due to inhibition of
the afferent visual impulsesat the retina or lateral geniculate
bodies. Theabnormal occipital discharges evoked by flash
stimu-lation could have spread via occipito-reticular path-ways or
utilising the dense visuo-motor (occipital-premotor cortex)
connections.20 The former possi-bility seems unlikely in view of
(a) the short latency(30 ms) between the primary complex of the
VEPsand the myoclonic jerking in the arms, and (b), thesmall size
and significance of visuo-reticular path-ways in humans.2' On the
other hand a cortico-cortical link is favoured by experimental
findings inthe photosensitive baboon22 23 and in a recentpatient
with visual reflex myoclonus studied byShibasaki,24 in whom
evidence for occipito-frontaltransmission of the abnormal
discharges generatedby flash stimulation was obtained.
Interestingly, theoccipito-frontal conduction time (10 ms)
recordedin Shibasaki's patient coincided almost exactly withour
indirect calculations (10-12 ms) in the twopatients reported here.
In addition, in these twopatients, cortical reflex myoclonus to
somaestheticstimuli was not modified by apomorphine orlevodopa. It
is therefore unlikely that dopamineagonists suppressed visual
reflex myoclonus by wayof a nonspecific inhibitory action or by
decreasingthe excitability of cortico-spinal
motoneurons.Accordingly we propose that the antimyocloniceffect of
the dopamine agonist was probably due to aselective inhibition of
visual cortex output neurons(area 19) projecting onto the premotor
cortex orinhibiting the "premotor" cortex neurons by whichvisual
cortex neurons communicate withmotoneurons in area 4.2022The main
source of cortical dopamine arises from
the basal ganglia via the meso-cortical dopaminergicpathway.25
In patient 1, and probably in patient 2,there was severe damage of
the entire substantianigra and surrounding structures. It is
therefore
Obeso, Artieda, Tunion, Luquin, Lage
likely that the dopaminergic meso-cortical pathwaywas damaged as
part of the multisystem atrophythey suffered. Direct
microiontophoretic applicationof dopamine mainly produces neuronal
inhibition26and endogenous dopamine activity in the visual cor-tex
is reduced by rhythmic flash (15 Hz) stimulationin cats.27 Thus,
dopamine agonists in these patientscould have restored an
intracortical inhibitorydopaminergic defect, made clinically overt
duringrepetitive visual stimulation, by post-synaptic stimu-lation
of the meso-cortical connections. On theother hand, reflex
myoclonus of any type is not afeature of untreated Parkinson's
disease, the besthuman model of dopaminergic deficiency. Someother
factor(s) must be taken into consideration toexplain the origin and
response to dopamine agon-ists of visual reflex myoclonus. In the
two patientsdescribed here there was evidence of marked cere-bellar
damage. Indeed, in many patients with corti-cal myoclonus, clinical
and CT scan features raisethe possibility that a defect of
cerebellar inhibitoryoutput is responsible for the pathological
corticalreflex mechanisms.'6 At present however, anyattempt to
explain how cerebellar and meso-corticaldysfunction interact to
provoke visual corticol myoc-lonus would be mere speculation.The
findings reported here confirm previous
results indicating that pure dopamine agonists arenot active
against somaesthetic cortical reflex myoc-lonus.'7 Unfortunately,
it was not possible to test theeffect of 5-HTP plus carbidopa upon
the visualreflex myoclonus present in our two patients.Experimental
evidence suggests that serotonin agon-ists are also capable of
suppressing photomyoclonicand photoconvulsive responses.28 Whether
or notthis is the case in humans requires further
investiga-tion.
Cortical reflex myoclonus is difficult to treat andmay be
associated with generalised seizures.'6Appropiate control of
visually triggered myoclonusoften improves the standard of living
of patientswith myoclonic epilepsy. Dopamine agonists mightbe
considered as an additional therapeutic tool inpatients with photic
epilepsy.
The authors are grateful to Mrs MA Garcia and MrsM Obeso for
technical help. Mrs ML Sola patientlytyped the manuscript.
References
Lhermitte F, Petrafaldi M, Marteau R, Gazengel J, Ser-dam M.
Analyse pharmacologique d'un cas de myo-clonies d'intention et d'
action post-anoxiques. RevNeurol (Paris) 1971; 124:21-31.
2 Lhermitte R, Marteau R, Degos CF. Analyse phar-macologique
d'un nouveau cas de myoclonies d'inten-
Protected by copyright.
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eurol Neurosurg P
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Decem
ber 1985. Dow
nloaded from
http://jnnp.bmj.com/
-
Dopamine agonists suppress visual-cortical reflex myoclonus
tion et d' action post-anoxiques. Rev Neurol (Paris)1972;
126:107-14.
3Chadwick D, Hallett M, Harris R, Jenner P, ReynoldsEH, Marsden
CD. Clinical, biochemical, andphysiological features distinguishing
myoclonusresponsive to 5-hydroxytryptophan, tryptophan with
amonoamine oxidase inhibitor and Clonazepam. Brain1977;
100:455-87.
4 Growdon JH, Young RR, Shahani T. L-5 hydroxytryp-tophan in
treatment of several different syndromes inwhich myoclonus is
prominent. Neurology (Minneap)1976;26: 1135-40.
5 Van Woert MH, Sethy VH. Therapy of intention myoc-lonus with
L-5 hydroxytryptophan and a peripheraldecarboxylase inhibitor, MK
486. Neurology (Min-neap) 1975;25:135-40.
6 Van Woert MH, Rosenbaum D, Howilson J, BowersMB. Long-term
therapy of myoclonus and otherneurologic disorder with
L-5-hydroxytryptophan andCarbidopa. N Engl J Med
1977;296:70-75.
7 Chadwick D, Harris R, Jenner P, Reynolds EH, Mars-den CD.
Manipulation of brain serotonin in the treat-ment of myoclonus.
Lancet 1975;2:434-5.
8 Van Woert MH, Rosenbaum D. L-5-hydroxytryptophantherapy in
myoclonus. In: Fahn S, Davis JN, RowlandPL, eds. Advances in
Neurology, Vol. 26. New York:Raven Press. 1979:109-22.
Glatt S, Klawans HL, Weiner WJ, Prelevic S. Myoclonicdisorders
responsive to serotoninergic blockade.Neurology (Minneap) 1979;29:
606-7.
0O Thal LJ, Sharpless NS, Wolfson L, Katzman R. Treat-ment of
myoclonus with L-5-Hydroxytryptophan andCarbidopa: Clinical,
electrophysiological, andbiochemical observations. Ann Neurol 1980;
7: 570-6.
" Meldrum BS. Mode of action of anticonvulsant drugs:biochemical
effects. The treatment of epilepsy. In:Tyrer JH, ed. Current Status
ofModern Therapy. Vol.5. Lancaster: MTP Press, 1980:29-59.
12 Meldrum BS. Photosensitive epilepsy in Papio papio as amodel
for drug studies. In: Cobb WA, Van Duijn H,eds. Contemporary
Clinical Neurophysiology (EEGSuppl. 34), Amsterdam: Elsevier,
1978:317-22.
'3 Quesney LF, Andermann F, Lal L, Nauseida PA. Trans-ient
abolition of generalized photosensitive epilepticdischarge in
humans by apomorphine, a dopaminereceptor agonist. Neurology
(Minneap) 1980;30:1169-74.
'4`Dawson GD. Investigations on a patient subject tomyoclonic
seizures after sensory stimulation. J NeurolNeurosurg Psychiatry
1977; 10: 141-62.
'5 Hallett M, Chadwick D, Marsden CD. Cortical reflexmyoclonus.
Neurology (Minneap) 1979;29: 1107-25.
16 Obeso JA, Rothwell JC, Marsden CD. The spectrum ofcortical
myoclonus. Brain 1985; 108: 193-224.
'' Obeso JA, Rothwell JC, Quinn NP, Lang AC, Thomp-son C,
Marsden CD. Cortical reflex myoclonusresponds to intravenous
Lisuride. Clin Neurophar-macology 1983;6:231-40.
18 Rothwell JC, Obeso JA, Marsden CD. On thesignificance of
giant somatosensory evoked potentialsin cortical myoclonus. J
Neurol Neurosurg Psychiatry1984;47: 33-42.
9 Quesney LF, Andermann F, Gloor P. Role of adopaminergic
mechanism in generalized photosensi-tive epilepsy. Neurology (NY)
1981;31: 1542-4.
20 Haaxma R, Kuypers HGJM. Intrahemispheric corticalconnexional
and visual guidance of hand and fingermovements in the rhesus
monkey. Brain1975;98: 239-60.
21 Brodal A. Neurological Anatomy. New York, OxfordUniversity
Press, 1981.
22 Menini CH. Role du cortex frontal dans
r6pilepsiephotosensible du singe Papio papio. J Physiol
(Paris)1976; 72: 5-44.
23 Catier J, Charmasson G, et Christolomme A. Study
ofipsilateral cortico-cortical connections from the occip-ital lobe
in the photosensitive baboon. J Physiol(Paris) 1973;66: 93-100.
24 Shibasaki H. In: Fahn S, Marsden CD, Van Woert M,eds.
Myoclonus. New York: Raven Press, in press.
25 Moore RY, Bloom FE. Central catecholamine neuronsystems:
anatomy and physiology of the dopamine sys-tems. Ann Rev Neurosci
1978;1:129-169.
26 Reader TA, Ferron A, Descarries L, Jasper HH. Mod-ulatory
role for biogenic animes in the cerebral cortex.Microiontophoretic
studies. Brain Res 1979;160:217-29.
27 Reader TA, De Champlain J, Jasper H. Catecholaminesreleased
from cerebral cortex in the cat: decrease dur-ing sensory
stimulation. Brain Res 1976;111:95-108.
28 Wada JA, Balzamo E, Meldrum BS, Naquet R. Drugsmodifying
brain serotonin content and photosensitiv-ity in the Senegalese
baboon (Papio papio). Elec-troencephalogr Clin Neurophysiol
1972;33: 520-27.
1283
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