CLINICAUSCIENTIFIC NOTES
20. Poyurovsky M, Fuchs C, Weizman A. Low-dose mianserin in neurolcptic induced akathisia. Br J Psychiatry (in press; 1997).
21. Povlsen UJ, Noring U, Laurse AML, Korsgaard S, Gerlach J.
Effects of serotonergic and anticholinergic drugs in haloperidolinduced dystonia in Cebus monkeys. Clin Neuropharmacol 1986;
9: 84-90,
22. Korsgaard S, Friis T. Effects of mianserin in neuroleptic-induced
1978;59:79-84.
parkinsonism. Psychopharmucolog~~

Apraxia of Eyelid Closure Accompanied by Denial
of Eye Opening
The inability to close the eyelids voluntarily on command
while retaining spontaneous blinking was first described by
Roth in 1901 as a “pseudobulbar paralysis” phenomenon (1).
In 1907, Lewandowsky was the first to designate this deficit as
“Apraxie des Lidschlusses,” an apraxia of eyelid closure (2).
The loss of voluntary closure of the eyelids has been observed
by other investigators, mostly in patients with diffuse, bilateral
cerebral abnormalities (3-9).
In this article, we describe the clinical, evoked corneal and
blink reflex, and computed tomographic (CT) findings in a
patient who exhibited apraxia of eyelid closure. In addition, he
also denied that his eyes remained open after attempts to close
them. To our knowledge, such a deficit has not been reported
before in patients with apraxia of eyelid closure.

Case Report
This 77-year-old right-handed man was admitted to our department because of an acute left-sided hemiplegia that had
resulted in postural imbalance that, in turn, had led to a fall and
a cerebral concussion with loss of consciousness for -10 min
and posttraumatic amnesia for a few minutes. He had hypertension, diabetes mellitus type 11, and Wolf-Parkinson-White
syndrome, and had experienced three previous myocardial infarctions and a number of transient ischemic attacks in the
vascular area of the carotid artery.
Examination at the time of admission revealed an alert, cooperative, and normotensive man with a regular pulse rate of 75
beatslmin. He was fully conscious; was normally oriented in
time, place, and person; and exhibited no aphasia. His head and
eyes deviated to the right. He was slightly dysarthric and had a
left hemianopsia and a slight left-sided central facial paresis.
The corneal reflex was normal on both sides. There was a
severe left-sided hemiplegia and a left-sided hemianalgesia, of
which he was aware. The deep tendon reflexes were all present.
The plantar response was flexor on the right side and extensor
on the left side. Two days after hospitalization, it was noticed
that the patient was unable to close his eyes voluntarily on
command, although they continued to blink spontaneously periodically. The corneal reflex was missing on both sides after
the left cornea was touched.

Received February 20, 1996; revision received September 7, 1996.
Accepted October 7, 1996.
Address correspondence and reprint requests to Dr. M. Aramideh at
Department of Neurology (H2-214), Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

1105

When requested to close his eyes, he contracted the corrugator supercilli muscles on both sides and the procerus muscle.
However, clinically there was no sign of contraction of either
orbicularis oculi muscle or of relaxation of the levator palpebrae superioris muscles. On command, he was able to wink
with the right eye, but not the left. Occasionally, when requested to close both eyes, he would contract either the frontalis muscles, and hence widen the eyes, or the orbicularis oculi
muscle on the right side unilaterally, despite our repeated urging. There was no Bell’s phenomenon. His visual threat reflex
was enhanced on both sides and often resulted in forceful closure of the eyelids. However, this was not a consistent finding.
Once the lids were closed passively, the patient was able to
keep them closed or to open them without difficulty.
The deviation of the head and eyes was resolved. The blink
rate was normal, as were the eye movements and the lid saccades in upward and downward directions. He slept with his
eyes closed. His response was normal to other requests, such as
opening and closing his mouth, showing his teeth, opening his
eyes widely, protruding his tongue, and turning his head. Also,
he demonstrated no apraxia of the limbs when following our
commands, such as “comb your hair” or “brush your teeth,”
and his higher cerebral functions were normal.
The patient denied that his eyes remained open after his
attempts to close them. Following our request that he close his
eyes and the question as to whether he thought the eyes were
closed, he answered, “Yes; I think so, yes; they are closed.”
When asked whether he could see fingers held up in front of
him, he answered, “Yes, I can see them.” Then, we asked him
to close his eyes and to continue trying until he could not see
the examiner’s fingers. He contracted the same aforementioned
muscles and his eyes remained open. To the question of whether his eyes were closed, he answered, “Yes; they are closed.”
To the question of how many fingers he saw now, he correctly
answered, “Two fingers.” When we told him that he should
not be able to see the fingers if his eyes were actually closed,
he reacted as follows: “Yes, that is curious; I cannot close my
eyes; how come?” Until then, he was unaware of his inability
to close his eyes. He still did not deny his left-sided hemiplegia.
The corneal and blink reflexes were evoked by techniques
reported earlier (10). For eliciting the corneal reflex, a small
metal sphere connected to an electronic trigger circuit was
used. The blink reflex was elicited by electrical stimulation of
the supraorbital nerve on both sides. A touch of the right cornea
elicited a normal response in the ipsilateral orbicularis oculi
muscle with a latency of 37 ms, and in the contralateral orbicularis oculi after a latent period of 43 ms, all within the normal
range. To the contrary, no responses could be elicited on either
side after the left cornea had been touched (Fig. 1). Stimulation
of the right or left supraorbital nerve elicited a normal ipsilateral early response (R1 latency, +12 ms). However, no ipsilateral or contralateral late response (R2) could be recorded from
the orbicularis oculi muscles after stimulation of either the right
or left supraorbital nerve.
A CT brain scan performed 1 week after hospitalization
showed a large, wedge-shaped infarction in the right parietal
lobe, in the vascular area of the posterior branches of the right
middle cerebral artery (Fig. 2). The lesion affected the lower
two-thirds of the parietal lobe, extended posteriorly to the occipital lobe, and affected anteriorly the lower half of the postcentral gyrus. The frontal and temporal lobes were unaffected.

Movement Disorders, Vol. 12, No. 6, 1997

CLINICAUSCIENTIFIC NOTES

1106

B
R
.

R

1

AWP

Tkig

- . - ; + ;
.

RrnP 1

.

H
10

ms

.

.

10 m
uV

SO

FhpP

2

.

FIG. 1. A: Stimulation of the right cornea (R*, two times) elicits a normal response on both sides. B: Stimulation of the left cornea (L*, two times)
elicits no response on either side

This lesion was not seen on earlier scans that were performed
several months before the ictus. Another old, small infarction,
as observed on earlier scans, was seen in the middle of the left
cerebellar hemisphere. Other findings were generalized cortical
atrophy and slightly enlarged ventricles. No sign of intracerebra1 hemorrhage was noted.

Discussion
Following a vascular accident in the right hemisphere, our
patient developed an apraxia in closing his eyelids and denied
that his eyes remained open when he had attempted to close
them. Most of the patients reported in the literature who could
not voluntarily close their eyes but retained spontaneous blinking appeared to have a bilateral cortical lesion. The three patients reported by Ross Russell (6) had Creutzfeldt-Jakob disease. According to this author, the site of the lesion is probably
in the cortical neurons rather than in the descending motor
fibers. Lessel (5) reported two cases: one patient with vascular
lesions involving both frontal lobes, and the other with amyotrophic lateral sclerosis with evidence of bilateral frontal disease. In other cases reported by Golbe et al. (8) and Jankovic
(7), the patients had progressive supranuclear palsy. In one case
recently reported by Abe et al. (9), the patient had neuronal loss
in the precentral gyri and frontal lobes. It must be emphasized

Movement Disorders, Vol. 12, No. 6, 1997

that the presence of a small lesion undetectable by CT cannot
be excluded in our patient's case.
Apraxia of eyelid closure because of a lesion in the right
hemisphere in a right-handed person, as in our patient, has also
been reported by Lewandowsky ( 2 ) in a patient with a sudden
left-sided hemiparesis. This patient was also unaware that he
was unable to close his eyes voluntarily. An associated denial
that the eyes remained open on attempts to close them, as in the
case in our patient, was not mentioned.
According to Liepmann (1 l), lesions causing apraxia would
be found in the parietal lobes, in the precentral and postcentral
gyri and the foot of the first two frontal gyri, with the subjacent
part of the centrum semiovale, and in the corpus callosum. Our
patient had an infarct in the region of the posterior branch of the
right middle cerebral artery that affected, among others, the
postcentral region.
In view of the anatomic site of the lesion, another finding
was the absence of the corneal reflex on either side after the
stimulation of the left cornea. This finding is in accord with the
observation by Ongerboer de Visser (12), who found different
types of corneal reflex abnormalities after lesions of the lower
one-third of the postcentral region, the fibers of which probably
descend through the cerebral peduncle. With respect to postcentral influences on the corneal reflex, several authors have
noted that fibers from the lower part of the postcentral gyrus
project to the spinal trigeminal complex (13,14). If these pro-

CLINICAUSCIENTIFIC NOTES

1107

by clinicians. Failure of voluntary closure of the eyelids with
preservation of spontaneous blinking and denial of eye opening
can be observed in patients with a unilateral parietal lobe lesion
including the postcentral region.

Acknowledgment: We thank Dr. J. H. T. M. Koelman for
his helpful comments during preparation of the manuscript.
M. Aramideh
Department of Neurology and
Clinical Neurophysiology Unit
I. H. Kwa
J. W. M. Brans
J. D. Speelman
Department of Neurology
B. W. Ongerboer de Visser
Clinical Neurophysiology Unit

B. Verbeeten, Jr.
Department of Radiology
Academic Medical Center
Amsterdam, The Netherlands

References
FIG. 2. Computed tomographic scan demonstrating a wedge-shaped
hypodense area in the right posterior parietal region, extending to the
temporoparietal region, indicative of a large infarction in the area of the
posterior branches of the middle cerebral artery.

jections are involved in the corneal and blink reflexes, a lesion
involving these structures might explain alterations of these
reflexes in our patient and indicate that these projections exert
an excitatory influence.
Despite profound abnormality of the corneal and blink reflexes, spontaneous periodic blinking was fully preserved. Apparently, these two reflexes are more sensitive to altered activity of suprasegmental structures than is spontaneous blinking.
Unfortunately, we did not perform electromyographic recordings at the orbicularis oculi and the levator palpebrae superioris muscles to acquire additional information on the origin
of the failure of eyelid closure or to determine whether the
reciprocal activity between these two muscles was disturbed
(15,16). However, it seems that our patient’s inability to close
his eyes was caused by a failure in the inhibition of the tonic
activity of the levator palpebrae muscles and in the contraction
of the orbicularis oculi muscles.
Our patient was unable to close his lids and, furthermore, he
denied that his lids remained open following his attempts to
close them. Apparently, persistence of object perception does
not simply result in awareness of involuntary eyelid opening
and of inability to close the lids. It seems that the lesion in our
patient has modified neuronal circuits in such way that his
intention to close his eyes has become sufficient to create the
thought that his eyes have been closed. The phenomenon of
denial exhibited by our patient is similar to the denial of eye
closure exhibited by patients with acute stroke, as described by
Ellis and Small (17). An autopsy on one of their five patients,
who denied that the eyes remained closed on attempts to open
them, revealed a lesion in the frontoparietal region.
The denial of eye opening may be overlooked unless sought

1. Roth WC. Demonstration van Kranken mit Ophthalmoplegia. Neurol Centrulbl 1901;20:921-923.
2. Lewandowsky M. Ueber Apraxie des Lidschlusses. Berl Klin
Wochenschr 1907:44:92 1-923.
3. Schilder P. Die Encephalitis periaxialis diffusa (nehst Bemerkungen uher die Apraxie des Lidschlusses). Arch Psychiatr 1924;7 I:
327-356.
4. Hoyt WF, Loeffler JD. Neurology of the orbicularis oculi: anatomic, physiologic, and clinical aspects of lid closure. In: Smith JL,
ed. Neuro-ophthalmology; vol 2. St Louis: CV Mosby, 1965:167205.
5. Lessel S. Supranuclear paralysis of voluntary lid closure. Arch
Oplzthulmol 1972;88:241-244.
6. Ross Russell RW. Supranuclear palsy of eyelid closure. Bruin
198O;102:71-82.
7. Jankovic J. Reply to “Apraxia of eyelid opening in progressive
supranuclear palsy” [Letter]. Ann Neurol 1984:1S:115-116.
8. Golbe LI, Davis PH, Lepore FE.Eyelid movement abnormalities
in progressive supranuclear palsy. Mov Disord 1989;4:297-302.
9. Abe K, Fujimura H, Tatsumi C, Toyooka K, Yorifuji S, Yanagihara T. Eyelid “apraxia” in patients with motor neuron disease.
Muscle Nerve 199559529-632.
10. Ongerboer de Visser BW, Cruccu G. Neurophysiologic examination of the trigeminal, facial, hypoglossal, and spinal accessory
nerves in cranial neuropathies and brain stem disorders. In: Brown
WF, Bolton CF, eds. Clinical Electromyogruphy. Boston: Butterworth-Heinemann, 1993:61-92.
11. Liepmann H. Der weitere Krankheitsverlauf bei dem einseitig
Apraktischen und der Gehirnhefund auf Grund von Serienschnitten. Monatsschr Psychiatr Neurol 1906;19:217-243.
12. Ongerboer de Visser BW. Corneal reflex latency in lesions of the
lower postcentral region. Neurology 1981;31:701-707.
3. Jones EG, Wise SP. Size, laminar and columnar distribution of
efferent cells in the sensory-motor cortex of monkeys. J Comp
Neurol 1977; 175:391438.
1. Brodal P. The cortico-pontine projections in the rhesus monkey.
Bruin 1978: 101:251-284.
5. Aramideh M, Ongerboer de Visser BW, Devriese PP, Bour LJ,
Speelman JD. Electromyographic features of levator palpebrae
superioris and orbicularis oculi muscles in hlepharospasm. Brain
1994;117:27-38.

Movement Disorders, Vol. 12, No. 6, 1997

CLINICAUSCIENTIFIC NOTES

1108

16. Aramideh M, Ongerboer de Visser BW, Koelman JHTM, Speelman JD. Motor persistence of orbicularis oculi muscle in eyelid
opening disorders. Neurology 1995;45:897-902.
17. Ellis SJ, Smali M. Denial of’eye closure in acute stroke. Stroke
1994;2S:1958-1962.

Tardive Dyskinesia in a Neuroleptic-Naive Patient
With Bipolar-I Disorder: Persistent Exacerbation
After Lithium Intoxication

intention tremor, and ataxic gait with pronounced impairment
of righting reflexes. Serum lithium was measured at 1.1
m m oln (normal range, 0.6-1 .O). Lithium intoxication due to
insufficient fluid intake was diagnosed, and the lithium treatment was discontinued. The ataxia and intention tremor rapidly
subsided, but the chorea of the digits and the pronounced orofacial and abdominal dyskinesia persisted (despite treatment in
therapeutic dosages with trihexiphenidyl, tetrabenazine, sulpiride, tiapride, and biperiden) (see the videotape). A variation in
intensity was related to the patient’s mental state, with increased movement disorder during depressive episodes and reduction during periods of normality or mania.

Discussion
Tardive or persistent dyskinesia (TD) is recognized as occurring after chronic neuroleptic treatment for schizophrenia
and bipolar disorder. Although lithium is sometimes recommended as a treatment for TD ( I ) , studies have reported that the
incidence of TD does not seem to be less and may even increase when lithium is given in combination with neuroleptics
(2-7). With one exception (7), however, all articles of which
we are aware have reported the cases of patients who, at some
time of their illness, had received neuroleptics or carbamazepine. We now report the case of a patient who had never received neuroleptics, but who, after long-term treatment with
antidepressants and lithium for bipolar-I disorder, developed
orofacial dyskinesia that progressed to a severe generalized
dyskinetic disorder after lithium intoxication.

Case Report
A 72-year-old single Caucasian woman had been diagnosed
with bipolar-I disorder when she was in her 20s. She had been
treated for >20 years in our hospital with lithium maintenance
therapy and doxepin or amitriptyline. Discontinuing the antidepressant and increasing lithium dosage were sufficient to
control her relatively uncommon manic phases so that no neuroleptic treatment was administered. A detailed review of our
hospital records and interviews with the patient and her attending physician disclosed no evidence of dopamine antagonist
use, including over-the-counter medications. In 1991, the patient developed a transient orofacial dyskinesia for the first time
during a depressive episode. The results of electroencephalography, Doppler sonography, electromyography, computed tomographic brain scan, and a laboratory screen including thyroid
tests, antistreptolysin 0, copper, and ceruloplasmin were normal. A treatment trial with tiapride was ineffective, but the
dyskinesia subsided when the depressive phase waned.
In September 1994, the patient was readmitted because of
ataxic gait, slurred speech, and disorientation. She was obtunded, dehydrated, and had pronounced orolingual-facial dyskinesia with a slow and slurred speech, occasional blepharospasm, and abdominal dyskinesia compromising speech and
respiration. She also had chorea of the toes and fingers, a slight

A videotape accompanies this article.
Received December 18, 1995; revisions received April 25 and June
25, 1996. Accepted February 22, 1997.
Address correspondence and reprint requests to Dr. A. MeyerLindenberg at Zentrum fur Psychiatrie, Justus-Liebig-Universitat, Am
Steg 22, 35385 GieRen, Germany.

M o w m m t Disorders, Vol. 12, No. 6, 1997

This patient is remarkable for developing severe persistent
dyskinesia in the absence of dopamine antagonists. The persistent exacerbation of TD after lithium intoxication raises the
possibility of lithium as a pathogenic agent. We have been able
to locate only one case in the literature of TD appearing after
lithium monotherapy. In that report (7), TD also appeared with
symptoms that strongly suggested lithium toxicity in a woman
aged 63. Unlike our case, the TD improved markedly with
lithium discontinuation. Whereas previous attempts to explain
this phenomenon have focused on the lithium’s augmentation
of neuroleptic effect on dopaminergic and noradrenergic receptors (6), our observation suggests that lithium may have an
intrinsic capacity to induce TD. Marked effects of lithium on
dopaminergic and serotonergic neurotransmission, altering
basal ganglia function, have been described (8). The elderly
may be especially vulnerable, even at serum levels in the highnormal range (9, LO). The observation that our patient’s TD
increased during depressive episodes and decreased during
manic or euthmyic episodes confirms previous reports that
have shown the same pattern of fluctuation of TD in bipolar
illness (1 1,12).
A contribution of antidepressant medication to the causation
of TD in this patient cannot be excluded. Although we are not
aware of confirmed reports of TD resulting from treatment with
doxepin or amitriptyline (acute dystonias have been seen, however) ( I 3), other antidepressants, especially selective serotonin
reuptake inhibitors, have been implicated in the pathogenesis of
TD in a number of cases (14,1.5).
Although the efficacy of lithium in the treatment of bipolar-I
disorder is undoubted, this case recommends, in our view, vigilance in the recognition of TD, especially in the elderly and if
treatment is prolonged. If patients develop abnormal movements while on lithium therapy, treatment alternatives such as
carbamazepine should be considered.

Legend to the Videotape
This 72-year-old Caucasian woman has bipolar-I disorder
with orofacial dyskinesia and abdominal involuntary movements. The persistent dyskinesia developed after lithium intoxication in the absence of dopamine antagonists.
A. Meyer-Lindenberg
B. Krausnick
Center for Psychiatry
School of Medicine
Justus Liebig University
Giessen, Germany