Seizure-Induced Miosis and Ptosis: Association With Temporal Lobe Magnetic Resonance Imaging Abnormalities Adel K. Afifi, MD; James J. Corbett, MD; H.
Stanley Thompson, MD;
Kristen K. Wells, MD
Abstract Two
patients with seizure-associated miosis and ptosis are described. In both there are magnetic resonance imaging abnormalities of the temporal lobe. In one patient, increased magnetic resonance imaging signal intensity is present in the temporal lobe contralateral to ptosis and miosis. In the other, there is temporal lobe asymmetry with the smaller temporal lobe ipsilateral to the miotic pupil and ptotic lid. The relevant human and experimental literature related to cortical control of pupil size and lid movement is reviewed. Based on the available literature and the findings in these two patients, it is proposed that the increased signal intensity in the temporal lobe of one patient represents an irritative stimulus causing contralateral miosis and ptosis, whereas the temporal lobe hypoplasia in the second patient permitted impulses from the contralateral normal temporal lobe to predominate, resulting in miosis and ptosis homolateral to the hypoplastic temporal lobe. (J Child Neurol 1990;5:142-146).
dilatation of the
pupils is a common autonomic accompaniment of seizures. Unilateral mydriasis, miosis, or ptosis as ictal or postictal occurrences are, however, rare. Their significance and pathophysiology are not well established. We report two such cases, describe relevant magnetic resonance imaging (MRI) abnormalities, and review the relevant clinical and experimental literature.
Bilateral
Patients ’
Case 1 M.H. is a 14-year-old white girl who was referred to the child neurology clinic by a neuro-ophthalmologist for evaluation and management of complex partial seizures. She was the product of a normal pregnancy and uncompli-
Received March 20, 1989. Received revised June 6, 1989. for publication June 8, 1989. From the Departments of Pediatrics, Neurology, Ophthalmology, and Anatomy, College of Medicine, University of Iowa, Iowa City, IA. Address correspondence to Dr Atiti, Uivision ot Child Neurology, Department of Pediatrics, The University of Iowa Hospital and Clinics, Iowa City, IA 52242.
Accepted
142
cated vaginal delivery. Birth weight was 3200 g. Her development was normal. At the age of 4 years, she developed fever, &dquo;viral-like&dquo; symptoms and became lethargic. General physical and neurologic examinations then were normal except for a right-sided Babinski reflex. Cerebrospinal fluid examination revealed 59 white blood cells, 81% lymphocytes, a glucose concentration of 121 mg/dL, and a protein concentration of 71 mg/dL. The diagnosis of viral encephalitis was made. She recovered without neurologic sequelae. Two years following this episode, she began to have complex partial seizures. These consisted of brief spells of altered sensorium associated with lip smacking. An electroencephalogram was mildly abnormal due to recurrent, medium- to high-voltage, irregular delta-theta sharp wave bursts from the right temporal area. The seizures responded well to phenytoin. The parents then elected to discontinue phenytoin, and seizures recurred in clusters of about 5 to 6 per week, with periods in between of up to 1 month without seizures. Five days prior to her clinic visit, her mother noticed that the child’s left eyelid was intermittently drooping. During the ophthalmologic examination, the neuro-ophthalmologist witnessed a spell of lip smacking, altered sensorium, and a look of distress on her face, after which left lid ptosis was noted for about 10 minutes. On further questioning, the mother and the family pediatrician reported that left lid ptosis was associated with the seizure clusters and that it disappeared when seizures were controlled with phenytoin. Observation of the patient over several months revealed intermittent postictal left ptosis
(Figure 1) and miosis lasting up to 30 minutes in association with some but not all seizure episodes. Neurologic examinations on several occasions were normal. Acetylcholine receptor antibody titer and thyroid function tests were normal. Electroencephalography revealed occasional sharp wave and spike discharges from the right temporal region. Computed tomographic (CT) scan was normal. MRI (Figure 2) revealed, on the T~-weighted images, a bright signal intensity in the right temporal area. No temporal lobe abnormality was seen on TI-weighted images. The temporal horns were bilaterally symmetrical. She was started on carbamazepine and shifted to phenytoin because of a drug rash. In spite of adequate blood levels, the child continued to have infrequent seizures, some of which were associated with left lid droop. The MRI abnormality remained unchanged over a 1-year period of observation.
Case 2 J.B. is a 12-year-old white girl referred to the child neurology clinic for evaluation of seizures and anisocoria. She was well until 3 months before her clinic visit, when she developed a temperature of 38.9°C and &dquo;flu&dquo;-like respiratory symptoms. The following day she appeared confused and had an unsteady gait requiring assistance to walk. On the way to the local hospital, she developed a generalized tonic-clonic seizure. Results of evaluation included a normal cerebrospinal fluid examination, chest radiograph, blood count, electroencephalogram, and CT scan. She was given phenobarbital. On follow-up examination, her pediatrician noted anisocoria and referred her for further evaluation. Examination revealed an alert, pleasant girl. Mild left ptosis and miosis were noted. Pupils were reactive to light and accommodation. Extraocular movements were full. Disks were sharp. The rest of the general physical and neurologic findings were normal. MRI (Figure 3) revealed asymmetry of the temporal lobes, not due to head rotation, with the left temporal lobe being smaller than the right. The temporal horns and skull thickness were bilaterally symmetrical. When seen 3 months later, she was still on phenobarbital and reported no seizures. Physical and neurologic examina-
FIGURE 1
Photograph
of
case
1
showing left ptosis.
FIGURE 2
T2-weighted (TR 2000 ms, TE 80 ms) MRI of case 1 showing increased signal intensity in the right temporal =
lobe
=
(arrows).
tions produced normal results. There anisocoria or ptosis.
was no
evidence of
Discussion The two patients reported in this communication share the association of clinical seizures with intermittent or transient miosis and ptosis. In both, there are MRI abnormalities of the temporal lobe. In the first patient, the temporal lobe abnormality consists of increased signal intensity contralateral to the miosis and ptosis. In the second patient, there is temporal lobe hypoplasia ipsilateral to the miotic pupil and ptotic lid. Reports of pupillary and lid abnormalities in association with seizures in humans are scarce. A total of 14 such cases has been reported to our knowledge in the English literature; most are single reports. In none was MRI performed. In 1900, Wilbrand and Sanger~ reviewed 25 cases of &dquo;cortical&dquo; ptosis, three of which had seizures and bilateral ptosis associated with lesions in the parietotemporal region and around the angular gyrus. Ptosis was more marked contralateral to the cerebral lesion. Cogan2 in 1956 described one patient with mild left ptosis and seizures in association with right temporo- ~ occipital lesion. There was no mention of the type of cerebral lesion or how it was found. It is, how3 ever, believed to be a non-space occupying lesion.3
143
FIGURE 3
Tl-weighted (TR 600 ms, TE = 20 ms) MRI of case 2 showing asymmetry of temporal lobes, the left temporal lobe being smaller. =
In 1966, Pant et al4 found, among 1000 cases of hospitalized seizure patients, six cases of either late ictal or postictal anisocoria associated with adversive seizures. The larger pupil was ipsilateral to the adversive eye movement. The authors believed that the larger pupil was the abnormal one because in some of the cases, it reacted sluggishly to light. This, however, was not consistent in all cases, since in one case the larger pupil reacted more briskly, in four cases both pupils reacted normally, and in one case both pupils reacted equally sluggishly. Walsh and Hoyt5 in 1969 reported one patient with right ptosis, right focal seizures, and a left temporal electroencephalographic focus. Walsh and HoytS also described their experience with rare cases in which an epileptic patient, usually a child, had occasional, brief episodes of unilateral mydriasis as an apparent expression of minor seizure activity. In 1974, Zee et al6 reported a patient with right-sided focal adversive
144
seizures associated with dilation of the right pupil due to a left middle frontal gyrus contusion. The report of Zee et al was the first to correlate pupil changes during seizures with a well-defined anatomic lesion seen at autopsy.6 Gadoth et aF in 1981 reported a patient with transient anisocoria (large right pupil) during right-sided focal seizures. The patient had a left frontal focus on electroencephalography. In 1987, Lowenstein et al8 described two cases of ptosis associated with arteriovenous malformations; in one, ptosis was ipsilateral to the focal seizures and contralateral to a frontal arteriovenous malformation; in the other, the ptosis was contralateral to a frontal arteriovenous malformation but was not associated with seizures. Experimental studies in both cats and monkeys have described changes in the size of pupils and lid movement in response to cortical and subcortical stimulation or ablation, and researchers have speculated about possible mechanisms and pathways by which these cortical and/or subcortical sites may influence pupil size and lid movement. Pitz is credited by Wang et al9 to be the first to report (in 1899) constriction of the contralateral pupil in rabbits following cortical stimulation at the boundary between the occipital and parietal lobes. In 1931, Wang et al9 reported bilateral pupillary constriction in cats following stimulation of certain areas of one occipital lobe. Hare et all° in 1935 reported constriction of the pupils following stimulation in the lateral wall of the lateral ventricle at the level of the rostral part of the lateral geniculate body. Barris11 in 1935 confirmed the earlier work of Wang et a19 and confined the cortical constrictor area in the cat to the boundary between Brodmann’s areas 19 (prestriate) and 36 (ectorhinic). He further observed that the pupillary constriction could not be elicited following repeated cortical stimulation and that bilateral cortical stimulation enhanced the constrictor effect of unilateral stimulation. Waller and Barris 12 in 1937 observed that ablation of the cortical pupilloconstrictor area in the occipital lobe of cats resulted in anisocoria, the contralateral pupil being larger. In 1942, Hodes and Magoun’3 identified separate pupilloconstrictor and pupillodilator areas in the frontal cortex of cats. The most effective pupilloconstrictor area was in the rostral extremity of the cingulate gyrus overlying the rostrum of the corpus callosum. Jampel 14 in 1960 reported bilateral pupillary constriction in the monkey following unilateral stimulation of frontal and occipital eye fields; the homolateral pupil was more constricted than the contralateral pupil. Stimulation of the superior temporal gyrus also produced ipsilateral
miosis without associated eye movement. Jampel 14 also noted the proximity and overlap in the frontal and occipital cortices of areas of pupillary constriction and dilation. Although there is clinical and experimental consensus as to the existence of a cortical pupillary constrictor area or areas, the pathway by which the cortex influences pupillary constriction is not yet well defined. Wang et al9 proposed that pupillary constriction following cortical stimulation was due to excitation of autonomic neurons in the EdingerWestphal component of the oculomotor nucleus. He provided evidence to suggest that corticofugal fibers in the cat reach the Edinger-Westphal nucleus via the rostral superior colliculus. Studies in the cat, on the other hand, show that the corticofugal fibers responsible for pupillary constriction synapse in the pretectal area rather than the superior colliculus.ll Hare et all0 identified the constrictor corticofugal fibers from the occipital lobe of the cat in the wall of the lateral ventricle at the level of the rostral part of the lateral geniculate body. From there, these fibers seem to enter the stratum zonale of the thalamus prior to their entry into the pretectal area. In addition to the experimental evidence cited above in support of the existence of cortical pupillary constrictor areas, there is parallel experimental evidence to suggest the existence of cortical pupillary dilator areas. These two areas are usually in close proximity to each other and may overlap with each other. Hodes and Magounl3 reported bilateral pupil-
lary dilation, more pronounced contralaterally following frontal lobe stimulation in the cat. The most effective cortical sites included the gyri proreus and genualis and parts of the anterior sigmoid, coronal, and orbital gyri. Jampel14 reported contraversive ocular deviation and bilateral pupillary dilation, greater in the contralateral pupil, following stimulation of middle frontal gyrus, whereas stimulation of other parts of the frontal lobe produced dilation of either the ipsilateral or the contralateral pupil with or without ocular movement. In contrast, stimulation of the occipital lobe produced contralateral eye deviation with pupil dilation. Usually both pupils dilate during a seizure, secondary to sympathetic overflow. The pathophysiology of unilateral pupillary dilatation or con.striction in seizures, however, is undetermined. Two mechanisms have been proposed 6, ’: an irritative process dilating the contralateral pupil and a paralytic (inhibitory) process inhibiting the dilation of the
ipsilateral pupil. Unilateral ptosis
is
extremely rare. To our knowledge, only single case reports are available in the English literature.2,5,8 Bilateral ptosis in association with focal seizures was reported in three additional patients. Unilateral and bilateral lid ptosis following stroke has been reported in a few cases.3,15,16 The anatomic basis of ptosis caused by cortical lesions has not been well defied. 17 Ptosis has been reported with unilateral temporal lobe, unilateral temporooccipital lobe, and bilateral frontal lobe lesions, as menon
three such
well
after infarctions in the distribution of the and less often the anterior, cerebral arteries. middle, The duration of cortical ptosis is highly variable. It may last a few minutes as an ictal or postictal phenomenon as in our case 1 or from 2 weeksl5 to 5 months or more3 when secondary to a cortical lesion. Cortical control of lid movement has been the subject of a number of studies in humans and experimental animals. Penfield and Rasmussenl8 reported eyelid opening in humans following unilateral stimulation of prefrontal, occipital, and, rarely, precentral cortex. Ferrier,19 and Leyton and Sherrington 20 reported bilateral eye opening in monkeys following stimulation of the second and third frontal convolutions. The eye opening in these animals was associated with simultaneous turning of eyes, head, and neck. Leyton and Sherrington 20 and Walker and Weaver 21 observed eye opening and adversive eye movement in the monkey following occipital lobe stimulation. In contrast to cortical stimulation, lesions in the frontal cortex22 have been associated with ptosis. The pathways from the cortex to the nuclei that mediate lid movement are not known but apparently are separate from those that produce conjugate eye movement.22 Considering the available evidence on cortical control of pupillary size and lid movement, it is surprising that alterations in pupil size and lid movement are not more frequently observed or reported. Two possible explanations for this discrepancy may be offered. The first is that alterations in pupil size and lid movement associated with cortical events are usually subtle and may be easly overlooked. The second is that the problem has not presented itself to the appropriate person. Most neuro-ophthalmologists witness seizures only rarely and have few opportunities to observe the pupils in the clinic setting. Conversely, neurologists witness seizures more frequently but do not think to look at the pupil at the time. Furthermore, eye blinking and forced eye closure prevent good observation of the as
pupils. The two children
as an
ictal
or
postictal pheno-
tion are, to
our
presented in this communicaknowledge, the first reported with 145
combined unilateral ptosis and miosis related to seizures and the only cases reported in whom a structural abnormality was present on MRI examination. In the first case, episodic miosis and ptosis represented either late ictal or early postictal occurrences associated with an increased signal intensity by MRI in the contralateral temporal lobe. The persistence of seizures permitted repeated documentation of the association of ptosis and miosis. In the second case, miosis and ptosis were transient events that occurred shortly after onset of seizures, disappeared along with seizure control, and were associated with hypoplasia of the ipsilateral temporal lobe. The relationship between the observed temporal lobe structural alterations and the ptosis and miosis is not certain. It may be argued that this is purely accidental. However, we believe this is unlikely in view of the available evidence relating different areas of the cerebral cortex, including the temporal lobes, to control of pupil size and lid movement. Pupil size and lid elevation are under control of the autonomic nervous system. Autonomic symptoms are common during seizures and especially during complex partial seizures. Some of these symptoms are attributed to hypothalamic activity triggered from the temporal lobe. The hyperprolactinemia associated with complex partial seizures of temporal lobe origin support such a relationship between the temporal lobe and the hypothalamus.23 Neural pathways from the temporal lobe to the hypothalamus are well established via the fornix, the stria terminalis, the medial forebrain bundle, and the ventral amygda24 lofugal tract. It is thus conceivable that the increased signal intensity in the temporal lobe of the first patient acted as an irritative stimulus causing anisocoria with contralateral miosis and ptosis, whereas the hypoplasia of the temporal lobe in the second patient permitted impulses from the contralateral normal temporal lobe to predominate, thus resulting in homolateral (to the hypoplastic lobe) miosis and ptosis. Obviously more cases need to be studied before a definitive statement can be made about the pathophysiology of seizure-induced anisocoria and
ptosis. References H, Sanger Neurologie des Auges. 1. Die Beziehungen des Nervensystems zu den Lidern, vol 1, Wiesbaden, Bergmann, 1900, pp 96-114.
1. Wilbrand
146
A: Die
2.
DG: Neurology of the Ocular Muscles, ed 2. Springfield, IL, Charles C. Thomas, 1956, pp 139-148.
Cogan
3. Nutt JG: Lid abnormalities secondary to cerebral hemisphere lesions. Ann Neurol 1977;1:149-151. 4. Pant SS, Benton JW, Dodge PR: Unilateral pupillary dilatation during and immediately following seizures. Neurology 1966; 16:837-840. 5. Walsh FB, Hoyt WF: Clinical Neuro-Ophthalmology, vol 1, ed 3. Baltimore, Williams & Wilkins, 1969, pp 297-304, 523. 6. Zee DS, Griffin J, Price DL: Unilateral pupillary dilatation during adversive seizures. Arch Neurol 1974;30:403-405. 7. Gadoth N, Margalith D, Bechar M: Unilateral pupillary dilatation during focal seizures.J Neurol 1981;225:227-230. 8. Lowenstein DH, Koch TK, Edwards MS: Cerebral ptosis with contralateral arteriovenous malformation: A report of two cases. Ann Neurol 1987;21:404-407. 9. Wang GH, Lu TW, Lau TT: Pupillary constriction from cortical stimulation. Chin J Physiol 1931;5:205-216. 10. Hare WK, Magoun HW, Ranson SW: Pathways for pupillary constriction: Location of synapses in the path for the pupillary light reflex and of constrictor fibers of cortical origin. Arch Neurol Psychiatry 1935;34:1188-1194. 11. Barris RW: A pupilloconstrictor area in the cerebral cortex of the cat and its relationship to the pretectal area. J Comp Neurol
1935;63:353-368. 12. Waller WH, Barris RW: Pupillary inequality in the cat following experimental lesions of the occipital cortex. Am J Physiol 1937; 120:144-149. 13. Hodes R, Magoun HW: Pupillary and other responses from
stimulation of the frontal cortex and basal telencephalon of the cat.J Comp Neurol 1942;76:461-473. 14. Jampel RS: Convergence, divergence, pupillary reactions and accommodation of the eyes from faradic stimulation of the macaque brain. J Comp Neurol 1960;115:371-399. 15. Caplan LR: Ptosis. J Neurol Neurosurg Psychiatry 1974;37:1-7. 16. Lepore FE: Bilateral cerebral ptosis. Neurology 1987;37: 1034-1046. 17. Miller NR: Anatomy and
physiology of normal and abnormal eyelid position and movement, in Walsh FB, Hoyt WF (eds): Clinical Neuro-Ophthalmology, ed 4. Baltimore, Williams & Wilkins, 1985, pp
936-938.
18. Penfield W, Rasmussen T: The Cerebral Cortex of Man, ed 2. New York, Hafner, 1968, pp 1-52, 67-76. 19. Ferrier D: Experiments on the brain of monkeys. Proc R Soc Lond 20.
1875;23:409-432. Leyton ASF, Sherrington CS: Observations cortex of the
Physiol
chimpanzee, orangutan,
and
on
the excitable
gorilla. Q J Exp
1917;11:135-222.
21. Walker AE, Weaver TA: Ocular movement from the occipital lobe in the monkey. J Neurophysiol 1940;3:353-357. 22. Best F: Die Augenveränderungen bei den organischen nichtentzündlichen Erkrankugen des Zentralnervensystem, in Schieck F, Bruckner H (eds): Kurzes Handbuch der Ophthalmologie, vol 6. Berlin, Springer, 1931, pp 531-532. 23. Laxer KD, Mullooly JP, Howell B: Prolactin changes after seizures classified by EEG monitoring. Neurology 1985;35:31-35. 24. Afifi AK, Bergman RA: Basic Neuroscience, ed 2. Baltimore, Urban & Schwarzenberg, 1986, pp 217-218.
Stanley Thompson, MD;
Kristen K. Wells, MD
Abstract Two
patients with seizure-associated miosis and ptosis are described. In both there are magnetic resonance imaging abnormalities of the temporal lobe. In one patient, increased magnetic resonance imaging signal intensity is present in the temporal lobe contralateral to ptosis and miosis. In the other, there is temporal lobe asymmetry with the smaller temporal lobe ipsilateral to the miotic pupil and ptotic lid. The relevant human and experimental literature related to cortical control of pupil size and lid movement is reviewed. Based on the available literature and the findings in these two patients, it is proposed that the increased signal intensity in the temporal lobe of one patient represents an irritative stimulus causing contralateral miosis and ptosis, whereas the temporal lobe hypoplasia in the second patient permitted impulses from the contralateral normal temporal lobe to predominate, resulting in miosis and ptosis homolateral to the hypoplastic temporal lobe. (J Child Neurol 1990;5:142-146).
dilatation of the
pupils is a common autonomic accompaniment of seizures. Unilateral mydriasis, miosis, or ptosis as ictal or postictal occurrences are, however, rare. Their significance and pathophysiology are not well established. We report two such cases, describe relevant magnetic resonance imaging (MRI) abnormalities, and review the relevant clinical and experimental literature.
Bilateral
Patients ’
Case 1 M.H. is a 14-year-old white girl who was referred to the child neurology clinic by a neuro-ophthalmologist for evaluation and management of complex partial seizures. She was the product of a normal pregnancy and uncompli-
Received March 20, 1989. Received revised June 6, 1989. for publication June 8, 1989. From the Departments of Pediatrics, Neurology, Ophthalmology, and Anatomy, College of Medicine, University of Iowa, Iowa City, IA. Address correspondence to Dr Atiti, Uivision ot Child Neurology, Department of Pediatrics, The University of Iowa Hospital and Clinics, Iowa City, IA 52242.
Accepted
142
cated vaginal delivery. Birth weight was 3200 g. Her development was normal. At the age of 4 years, she developed fever, &dquo;viral-like&dquo; symptoms and became lethargic. General physical and neurologic examinations then were normal except for a right-sided Babinski reflex. Cerebrospinal fluid examination revealed 59 white blood cells, 81% lymphocytes, a glucose concentration of 121 mg/dL, and a protein concentration of 71 mg/dL. The diagnosis of viral encephalitis was made. She recovered without neurologic sequelae. Two years following this episode, she began to have complex partial seizures. These consisted of brief spells of altered sensorium associated with lip smacking. An electroencephalogram was mildly abnormal due to recurrent, medium- to high-voltage, irregular delta-theta sharp wave bursts from the right temporal area. The seizures responded well to phenytoin. The parents then elected to discontinue phenytoin, and seizures recurred in clusters of about 5 to 6 per week, with periods in between of up to 1 month without seizures. Five days prior to her clinic visit, her mother noticed that the child’s left eyelid was intermittently drooping. During the ophthalmologic examination, the neuro-ophthalmologist witnessed a spell of lip smacking, altered sensorium, and a look of distress on her face, after which left lid ptosis was noted for about 10 minutes. On further questioning, the mother and the family pediatrician reported that left lid ptosis was associated with the seizure clusters and that it disappeared when seizures were controlled with phenytoin. Observation of the patient over several months revealed intermittent postictal left ptosis
(Figure 1) and miosis lasting up to 30 minutes in association with some but not all seizure episodes. Neurologic examinations on several occasions were normal. Acetylcholine receptor antibody titer and thyroid function tests were normal. Electroencephalography revealed occasional sharp wave and spike discharges from the right temporal region. Computed tomographic (CT) scan was normal. MRI (Figure 2) revealed, on the T~-weighted images, a bright signal intensity in the right temporal area. No temporal lobe abnormality was seen on TI-weighted images. The temporal horns were bilaterally symmetrical. She was started on carbamazepine and shifted to phenytoin because of a drug rash. In spite of adequate blood levels, the child continued to have infrequent seizures, some of which were associated with left lid droop. The MRI abnormality remained unchanged over a 1-year period of observation.
Case 2 J.B. is a 12-year-old white girl referred to the child neurology clinic for evaluation of seizures and anisocoria. She was well until 3 months before her clinic visit, when she developed a temperature of 38.9°C and &dquo;flu&dquo;-like respiratory symptoms. The following day she appeared confused and had an unsteady gait requiring assistance to walk. On the way to the local hospital, she developed a generalized tonic-clonic seizure. Results of evaluation included a normal cerebrospinal fluid examination, chest radiograph, blood count, electroencephalogram, and CT scan. She was given phenobarbital. On follow-up examination, her pediatrician noted anisocoria and referred her for further evaluation. Examination revealed an alert, pleasant girl. Mild left ptosis and miosis were noted. Pupils were reactive to light and accommodation. Extraocular movements were full. Disks were sharp. The rest of the general physical and neurologic findings were normal. MRI (Figure 3) revealed asymmetry of the temporal lobes, not due to head rotation, with the left temporal lobe being smaller than the right. The temporal horns and skull thickness were bilaterally symmetrical. When seen 3 months later, she was still on phenobarbital and reported no seizures. Physical and neurologic examina-
FIGURE 1
Photograph
of
case
1
showing left ptosis.
FIGURE 2
T2-weighted (TR 2000 ms, TE 80 ms) MRI of case 1 showing increased signal intensity in the right temporal =
lobe
=
(arrows).
tions produced normal results. There anisocoria or ptosis.
was no
evidence of
Discussion The two patients reported in this communication share the association of clinical seizures with intermittent or transient miosis and ptosis. In both, there are MRI abnormalities of the temporal lobe. In the first patient, the temporal lobe abnormality consists of increased signal intensity contralateral to the miosis and ptosis. In the second patient, there is temporal lobe hypoplasia ipsilateral to the miotic pupil and ptotic lid. Reports of pupillary and lid abnormalities in association with seizures in humans are scarce. A total of 14 such cases has been reported to our knowledge in the English literature; most are single reports. In none was MRI performed. In 1900, Wilbrand and Sanger~ reviewed 25 cases of &dquo;cortical&dquo; ptosis, three of which had seizures and bilateral ptosis associated with lesions in the parietotemporal region and around the angular gyrus. Ptosis was more marked contralateral to the cerebral lesion. Cogan2 in 1956 described one patient with mild left ptosis and seizures in association with right temporo- ~ occipital lesion. There was no mention of the type of cerebral lesion or how it was found. It is, how3 ever, believed to be a non-space occupying lesion.3
143
FIGURE 3
Tl-weighted (TR 600 ms, TE = 20 ms) MRI of case 2 showing asymmetry of temporal lobes, the left temporal lobe being smaller. =
In 1966, Pant et al4 found, among 1000 cases of hospitalized seizure patients, six cases of either late ictal or postictal anisocoria associated with adversive seizures. The larger pupil was ipsilateral to the adversive eye movement. The authors believed that the larger pupil was the abnormal one because in some of the cases, it reacted sluggishly to light. This, however, was not consistent in all cases, since in one case the larger pupil reacted more briskly, in four cases both pupils reacted normally, and in one case both pupils reacted equally sluggishly. Walsh and Hoyt5 in 1969 reported one patient with right ptosis, right focal seizures, and a left temporal electroencephalographic focus. Walsh and HoytS also described their experience with rare cases in which an epileptic patient, usually a child, had occasional, brief episodes of unilateral mydriasis as an apparent expression of minor seizure activity. In 1974, Zee et al6 reported a patient with right-sided focal adversive
144
seizures associated with dilation of the right pupil due to a left middle frontal gyrus contusion. The report of Zee et al was the first to correlate pupil changes during seizures with a well-defined anatomic lesion seen at autopsy.6 Gadoth et aF in 1981 reported a patient with transient anisocoria (large right pupil) during right-sided focal seizures. The patient had a left frontal focus on electroencephalography. In 1987, Lowenstein et al8 described two cases of ptosis associated with arteriovenous malformations; in one, ptosis was ipsilateral to the focal seizures and contralateral to a frontal arteriovenous malformation; in the other, the ptosis was contralateral to a frontal arteriovenous malformation but was not associated with seizures. Experimental studies in both cats and monkeys have described changes in the size of pupils and lid movement in response to cortical and subcortical stimulation or ablation, and researchers have speculated about possible mechanisms and pathways by which these cortical and/or subcortical sites may influence pupil size and lid movement. Pitz is credited by Wang et al9 to be the first to report (in 1899) constriction of the contralateral pupil in rabbits following cortical stimulation at the boundary between the occipital and parietal lobes. In 1931, Wang et al9 reported bilateral pupillary constriction in cats following stimulation of certain areas of one occipital lobe. Hare et all° in 1935 reported constriction of the pupils following stimulation in the lateral wall of the lateral ventricle at the level of the rostral part of the lateral geniculate body. Barris11 in 1935 confirmed the earlier work of Wang et a19 and confined the cortical constrictor area in the cat to the boundary between Brodmann’s areas 19 (prestriate) and 36 (ectorhinic). He further observed that the pupillary constriction could not be elicited following repeated cortical stimulation and that bilateral cortical stimulation enhanced the constrictor effect of unilateral stimulation. Waller and Barris 12 in 1937 observed that ablation of the cortical pupilloconstrictor area in the occipital lobe of cats resulted in anisocoria, the contralateral pupil being larger. In 1942, Hodes and Magoun’3 identified separate pupilloconstrictor and pupillodilator areas in the frontal cortex of cats. The most effective pupilloconstrictor area was in the rostral extremity of the cingulate gyrus overlying the rostrum of the corpus callosum. Jampel 14 in 1960 reported bilateral pupillary constriction in the monkey following unilateral stimulation of frontal and occipital eye fields; the homolateral pupil was more constricted than the contralateral pupil. Stimulation of the superior temporal gyrus also produced ipsilateral
miosis without associated eye movement. Jampel 14 also noted the proximity and overlap in the frontal and occipital cortices of areas of pupillary constriction and dilation. Although there is clinical and experimental consensus as to the existence of a cortical pupillary constrictor area or areas, the pathway by which the cortex influences pupillary constriction is not yet well defined. Wang et al9 proposed that pupillary constriction following cortical stimulation was due to excitation of autonomic neurons in the EdingerWestphal component of the oculomotor nucleus. He provided evidence to suggest that corticofugal fibers in the cat reach the Edinger-Westphal nucleus via the rostral superior colliculus. Studies in the cat, on the other hand, show that the corticofugal fibers responsible for pupillary constriction synapse in the pretectal area rather than the superior colliculus.ll Hare et all0 identified the constrictor corticofugal fibers from the occipital lobe of the cat in the wall of the lateral ventricle at the level of the rostral part of the lateral geniculate body. From there, these fibers seem to enter the stratum zonale of the thalamus prior to their entry into the pretectal area. In addition to the experimental evidence cited above in support of the existence of cortical pupillary constrictor areas, there is parallel experimental evidence to suggest the existence of cortical pupillary dilator areas. These two areas are usually in close proximity to each other and may overlap with each other. Hodes and Magounl3 reported bilateral pupil-
lary dilation, more pronounced contralaterally following frontal lobe stimulation in the cat. The most effective cortical sites included the gyri proreus and genualis and parts of the anterior sigmoid, coronal, and orbital gyri. Jampel14 reported contraversive ocular deviation and bilateral pupillary dilation, greater in the contralateral pupil, following stimulation of middle frontal gyrus, whereas stimulation of other parts of the frontal lobe produced dilation of either the ipsilateral or the contralateral pupil with or without ocular movement. In contrast, stimulation of the occipital lobe produced contralateral eye deviation with pupil dilation. Usually both pupils dilate during a seizure, secondary to sympathetic overflow. The pathophysiology of unilateral pupillary dilatation or con.striction in seizures, however, is undetermined. Two mechanisms have been proposed 6, ’: an irritative process dilating the contralateral pupil and a paralytic (inhibitory) process inhibiting the dilation of the
ipsilateral pupil. Unilateral ptosis
is
extremely rare. To our knowledge, only single case reports are available in the English literature.2,5,8 Bilateral ptosis in association with focal seizures was reported in three additional patients. Unilateral and bilateral lid ptosis following stroke has been reported in a few cases.3,15,16 The anatomic basis of ptosis caused by cortical lesions has not been well defied. 17 Ptosis has been reported with unilateral temporal lobe, unilateral temporooccipital lobe, and bilateral frontal lobe lesions, as menon
three such
well
after infarctions in the distribution of the and less often the anterior, cerebral arteries. middle, The duration of cortical ptosis is highly variable. It may last a few minutes as an ictal or postictal phenomenon as in our case 1 or from 2 weeksl5 to 5 months or more3 when secondary to a cortical lesion. Cortical control of lid movement has been the subject of a number of studies in humans and experimental animals. Penfield and Rasmussenl8 reported eyelid opening in humans following unilateral stimulation of prefrontal, occipital, and, rarely, precentral cortex. Ferrier,19 and Leyton and Sherrington 20 reported bilateral eye opening in monkeys following stimulation of the second and third frontal convolutions. The eye opening in these animals was associated with simultaneous turning of eyes, head, and neck. Leyton and Sherrington 20 and Walker and Weaver 21 observed eye opening and adversive eye movement in the monkey following occipital lobe stimulation. In contrast to cortical stimulation, lesions in the frontal cortex22 have been associated with ptosis. The pathways from the cortex to the nuclei that mediate lid movement are not known but apparently are separate from those that produce conjugate eye movement.22 Considering the available evidence on cortical control of pupillary size and lid movement, it is surprising that alterations in pupil size and lid movement are not more frequently observed or reported. Two possible explanations for this discrepancy may be offered. The first is that alterations in pupil size and lid movement associated with cortical events are usually subtle and may be easly overlooked. The second is that the problem has not presented itself to the appropriate person. Most neuro-ophthalmologists witness seizures only rarely and have few opportunities to observe the pupils in the clinic setting. Conversely, neurologists witness seizures more frequently but do not think to look at the pupil at the time. Furthermore, eye blinking and forced eye closure prevent good observation of the as
pupils. The two children
as an
ictal
or
postictal pheno-
tion are, to
our
presented in this communicaknowledge, the first reported with 145
combined unilateral ptosis and miosis related to seizures and the only cases reported in whom a structural abnormality was present on MRI examination. In the first case, episodic miosis and ptosis represented either late ictal or early postictal occurrences associated with an increased signal intensity by MRI in the contralateral temporal lobe. The persistence of seizures permitted repeated documentation of the association of ptosis and miosis. In the second case, miosis and ptosis were transient events that occurred shortly after onset of seizures, disappeared along with seizure control, and were associated with hypoplasia of the ipsilateral temporal lobe. The relationship between the observed temporal lobe structural alterations and the ptosis and miosis is not certain. It may be argued that this is purely accidental. However, we believe this is unlikely in view of the available evidence relating different areas of the cerebral cortex, including the temporal lobes, to control of pupil size and lid movement. Pupil size and lid elevation are under control of the autonomic nervous system. Autonomic symptoms are common during seizures and especially during complex partial seizures. Some of these symptoms are attributed to hypothalamic activity triggered from the temporal lobe. The hyperprolactinemia associated with complex partial seizures of temporal lobe origin support such a relationship between the temporal lobe and the hypothalamus.23 Neural pathways from the temporal lobe to the hypothalamus are well established via the fornix, the stria terminalis, the medial forebrain bundle, and the ventral amygda24 lofugal tract. It is thus conceivable that the increased signal intensity in the temporal lobe of the first patient acted as an irritative stimulus causing anisocoria with contralateral miosis and ptosis, whereas the hypoplasia of the temporal lobe in the second patient permitted impulses from the contralateral normal temporal lobe to predominate, thus resulting in homolateral (to the hypoplastic lobe) miosis and ptosis. Obviously more cases need to be studied before a definitive statement can be made about the pathophysiology of seizure-induced anisocoria and
ptosis. References H, Sanger Neurologie des Auges. 1. Die Beziehungen des Nervensystems zu den Lidern, vol 1, Wiesbaden, Bergmann, 1900, pp 96-114.
1. Wilbrand
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A: Die
2.
DG: Neurology of the Ocular Muscles, ed 2. Springfield, IL, Charles C. Thomas, 1956, pp 139-148.
Cogan
3. Nutt JG: Lid abnormalities secondary to cerebral hemisphere lesions. Ann Neurol 1977;1:149-151. 4. Pant SS, Benton JW, Dodge PR: Unilateral pupillary dilatation during and immediately following seizures. Neurology 1966; 16:837-840. 5. Walsh FB, Hoyt WF: Clinical Neuro-Ophthalmology, vol 1, ed 3. Baltimore, Williams & Wilkins, 1969, pp 297-304, 523. 6. Zee DS, Griffin J, Price DL: Unilateral pupillary dilatation during adversive seizures. Arch Neurol 1974;30:403-405. 7. Gadoth N, Margalith D, Bechar M: Unilateral pupillary dilatation during focal seizures.J Neurol 1981;225:227-230. 8. Lowenstein DH, Koch TK, Edwards MS: Cerebral ptosis with contralateral arteriovenous malformation: A report of two cases. Ann Neurol 1987;21:404-407. 9. Wang GH, Lu TW, Lau TT: Pupillary constriction from cortical stimulation. Chin J Physiol 1931;5:205-216. 10. Hare WK, Magoun HW, Ranson SW: Pathways for pupillary constriction: Location of synapses in the path for the pupillary light reflex and of constrictor fibers of cortical origin. Arch Neurol Psychiatry 1935;34:1188-1194. 11. Barris RW: A pupilloconstrictor area in the cerebral cortex of the cat and its relationship to the pretectal area. J Comp Neurol
1935;63:353-368. 12. Waller WH, Barris RW: Pupillary inequality in the cat following experimental lesions of the occipital cortex. Am J Physiol 1937; 120:144-149. 13. Hodes R, Magoun HW: Pupillary and other responses from
stimulation of the frontal cortex and basal telencephalon of the cat.J Comp Neurol 1942;76:461-473. 14. Jampel RS: Convergence, divergence, pupillary reactions and accommodation of the eyes from faradic stimulation of the macaque brain. J Comp Neurol 1960;115:371-399. 15. Caplan LR: Ptosis. J Neurol Neurosurg Psychiatry 1974;37:1-7. 16. Lepore FE: Bilateral cerebral ptosis. Neurology 1987;37: 1034-1046. 17. Miller NR: Anatomy and
physiology of normal and abnormal eyelid position and movement, in Walsh FB, Hoyt WF (eds): Clinical Neuro-Ophthalmology, ed 4. Baltimore, Williams & Wilkins, 1985, pp
936-938.
18. Penfield W, Rasmussen T: The Cerebral Cortex of Man, ed 2. New York, Hafner, 1968, pp 1-52, 67-76. 19. Ferrier D: Experiments on the brain of monkeys. Proc R Soc Lond 20.
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21. Walker AE, Weaver TA: Ocular movement from the occipital lobe in the monkey. J Neurophysiol 1940;3:353-357. 22. Best F: Die Augenveränderungen bei den organischen nichtentzündlichen Erkrankugen des Zentralnervensystem, in Schieck F, Bruckner H (eds): Kurzes Handbuch der Ophthalmologie, vol 6. Berlin, Springer, 1931, pp 531-532. 23. Laxer KD, Mullooly JP, Howell B: Prolactin changes after seizures classified by EEG monitoring. Neurology 1985;35:31-35. 24. Afifi AK, Bergman RA: Basic Neuroscience, ed 2. Baltimore, Urban & Schwarzenberg, 1986, pp 217-218.
