J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.43.11.1035 on 1 November 1980. Downloaded from

Journal of , Neurosurgery, and Psychiatry, 1980, 43. 1035-1040

Seizure-induced neglect

KENNETH M HEILMAN AND GREGORY J HOWELL From the Department of Neurology, College of Medicine, University of Florida, and the Veterans Administration Medical Center, Gainesville, Florida, USA

SUMMARY A man with intermittent right parieto-occipital seizures was monitored by electro- encephalography while he received 60 trials of being touched on the right, left, or both hands. Half of the trials were given during a focal seizure, and half were given interictally. While the patient was having seizures, he appropriately responded to all 10 stimuli delivered to the right hand, but four of 10 responses were incorrect (allaesthetic) when he was stimulated on the left. With bilateral simultaneous stimulation he neglected the left hand in all 10 trials. His interictal performance was flawless. When given a line-bisection task on two occasions during a seizure, the patient attempted to make a mark to the left of the entire sheet of paper. Immediately postictally he made a mark at the right end of the line. The case illustrates that focal seizures may induce elements of the neglect syndrome and that attention (to contralateral stimuli) and intention to perform (in the contralateral guest. Protected by copyright. hemispatial field) may be dissociable phenomena.

Under a variety of stimulus conditions, patients seen in the neglect syndrome, such as hemi- who can detect stimuli fail to report, respond, or spatial neglect, may be induced by an intentional orient to stimuli presented on the side contra- defect.4 6 Recently, we observed a patient with lateral to a cerebral lesion. The failure to report right parietal lobe seizures. The patient showed or respond appropriately to unilateral stimuli has that elements of the neglect syndrome may be been termed "unilateral neglect" or "inatten- associated with focal seizures. He also provided tion."' Sometimes patients with unilateral lesions evidence for the postulate that attentional and respond appropriately to unilateral stimuli but intentional defects are dissociable. fail to report the contralateral stimulus when stimulated on both sides simultaneously. Critch- Case report ley' thought that extinction to simultaneous stimulation is another instance of unilateral A 63 year old man was in good health until two neglect made manifest at a particular moment days before admission when he developed "impair- by the technique of simultaneous stimulation. ment of vision in the left eye." He had had difficulty When touched on the side seeing the chain on a night light. He attributed the opposite to their problem to impaired vision in the left eye because lesion, patients with unilateral neglect often re- the vision in his right eye was already poor secondary ported that they were touched on the side ipsi- to a cataract. He had no other specific complaints http://jnnp.bmj.com/ lateral to their lesion. This has been termed until the next morning when he began to have inter- "allaesthesia."2 Critchley' thought that unilateral mittent episodes of "double vision." During these neglect also was responsible for allaesthesia. episodes, everything seemed to move to the right Because inattention can be induced by a variety and appeared to have constantly fluctuating colours. of cortical and subcortical lesions, we have The patient did not complain of dizziness but did say postulated that many of the behavioural signs that during the two days before admission he had reflect an attention-arousal disorder induced by difficulty in walking, which was most severe during the episodes of "double vision." disruption of a corticolimbic reticular loop.3 4 We Past medical and family histories were non- on October 1, 2021 by have also postulated that some of the behaviour contributory. Medication included spironolactone with hydrochlorothiazide and digoxin. Physical exam- Address for reprint requests: Dr KM Heilman, Box J-236, Depart- ination showed the patient's temperature to be ment of Neurology, College of Medicine, University of Florida, Gainesville, FL 36i7'C; pulse rate, 80 beats per min and regular; 32610, USA. respirations, 16 per min and unlaboured; and blood Accepted 10 July 1980 pressure, 135/90 mmHg without postural change. 1035 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.43.11.1035 on 1 November 1980. Downloaded from

1036 Kenneth M Heilman and Gregory J Howell

Neurological examination showed an alert but half of the state. He would write his name in the indifferent right-handed man who was oriented in right upper quadrant of a sheet of paper and would time, place and person. He accurately named some incorrectly bisect a line too far to the right even of the preceding presidents and recalled major when he was able to identify correctly the left side current events. Despite distraction, he was able to re- of the line by searching for a letter at that end.5 call three objects five minutes after presentation, and His mood was generally eufphoric, but when told he he could recall seven numbers forward and four in was having seizures, he adamantly denied he was reverse order. There was no aphasia, acalculia, finger having anything but brief spells of "double vision." , or right-left confusion. Reading and writing When we tested for auditory extinction, the patient also were normal. The patient had difficulty drawing was asked to close his eyes. In the unilateral con- a cube, a square, and a triangle. He also appeared ditions (unilateral left, unilateral right), the examiner to have an indifferent affect. Several other tests simultaneously snapped the fingers of both the right of right-hemisphere function were performed. The and left hand approximately 5 cm from the patient's ability to judge mood from pictures of faces patient's right or left ear. In the bilateral condition, was incorrect6 in nine of 12 trials; he correctly the fingers of both hands were simultaneously identified only happy faces. In judging verbal mood, snapped; however, one hand was placed behind each he was incorrect in five of 12 trials; he would judge of the patient's ears. We randomised the order in what was said rather than how it was said. His which these three conditions were given. Tests for ability to create a mood with his own voice was tactile extinction were performed in a similar manner. impaired except for happy moods. Song recognition In the unilateral conditions, the back of the right or and spontaneous singing were normal. When asked left hand was touched. In the bilateral condition both to tell whether two pictures of unfamiliar faces were hands were simultaneously touched on the back. The the same or different, he made four errors in 12 order in which these conditions were given was trials. randomised. guest. Protected by copyright. The pupils were equal in size, round, and reacted Interictally, the patient was given 18 auditory to light and accommodation. Visual acuity in the trials, six in each condition, and 24 tactile trials, left eye was 20/70 with glasses; the patient could eight each condition. He flawlessly performed all of see only hand movements with the right eye because these trials. While he was having a seizure, he was of a dense cataract. There was a dense left homony- also given 18 auditory trials, six in each condition. mous visual field defect. The remainder of the cranial He flawlessly detected and lateralised all unilateral were normal. Motor examination, including stimuli; however, with bilateral simultaneous auditory muscle strength, tone, and coordination, was normal stimuli, he neglected the left-side stimulus in all six except for a tendency for the outstretched left arm trials. During a seizure he was also given 14 uni- to rise. Cerebellar testing, including finger-to-nose, lateral tactile stimuli (seven to each hand) and six heel-to-shin, and rapid alternating movements, was bilateral stimultaneous tactile stimuli. With unilateral normal. The patient walked cautiously and appeared right-hand tactile stimuli, his performance was flaw- to have slight bradykinesia of the left limbs. Deep less. With unilateral left-hand tactile stimuli, he tendon reflexes were normal except for absent ankle detected all seven stimuli, but on two of these trials jerks. The right plantar response was flexor, and the he thought he was being touched on the right hand left was equivocal. There were no other pathologic (allaesthetic response). With bilateral stimuli he reflexes. Sensory examination, including , pos- neglected left-hand stimulation in all six trials. ition, vibration, and graphesthesia, was normal except An EEG performed on the day of admission dis- for mild impairment of vibration in the distal portion closed occasional spikes and an occasional slow wave of both lower extremities. focus in the right parieto-occipital region. With the During the neurological examination the patient onset of the patient's sensation of diplopia, the

complained that an episode of "double vision" was record revealed polyspikes from the right parieto- http://jnnp.bmj.com/ beginning. His head and eyes then began to deviate occipital area that gradually increased in amplitude to the left. On command he could momentarily and rhythm with a decrease in frequency to approxi- return his head and eyes to the right; however, they mately two to three Hz sharp and slow wave dis- again promptly deviated to the left. The sensation charge that became generalised before returning to of diplopia was present even with his eyes closed. baseline rhythms (see figure). During this seizure the previously noted tendency While being monitored with the EEG, the patient for the outstretched left arm to rise increased, and received 60 trials of being touched on the right, the patient was slow to respond to questions but left, or both hands. Half of the trials were given answered appropriately. Because he had several com- during a seizure and half were given interictally. on October 1, 2021 by ponents of the neglect syndrome, special testing was The stimulus conditions were randomised. While he performed. was having a seizure, he correctly recognised all 10 During an interictal period, when asked to place stimuli delivered to the right hand, but when he was numbers on a clock, he incorrectly placed the num- touched on the left hand, four of 10 responses were bers only on the right half of the clock. When given incorrect (allaesthetic). With bilateral simultaneous a map of Florida, he located the cities in the right stimuilation he neglected the left hand in all 10 trials. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.43.11.1035 on 1 November 1980. Downloaded from

Seizure-induced neglect 1037

FP2

02

F3 T4 P Fig Electroencepha- logram recorded at onset of focal seizure. guest. Protected by copyright.

01 150j 2r3~~~~~~~~~~~~~~~~~~~~~~~I

T3

His interictal performance was flawless. When given normal haematocrit, white blood count, platelets, a line bisection task, on two occasions during a and erythrocyte sedimentation rate. The Veneral seizure, he had difficulty seeing the line; but when Disease Research Laboratory test for syphilis was encouraged to bisect the line on the sheet of paper nonreactive. Abnormal test results included: fasting directly in front of him, he attempted to make a glucose 11-9 mmol/l; serum cholesterol, 9-6 mmol/l; mark beyond the left edge of the entire sheet. Im- and triglyceride, 23-7 mmol/l; and lipoprotein http://jnnp.bmj.com/ mediately postictally, he made a mark at the right electrophoresis showed Type V hyperlipoproteinemia. end of the line. Several minutes later, although he The electrocardiogram and chest and skull X-ray continued to make a mark to the right side of the films were normal. A brain scan revealed increased line, his mark was more accurate. Also immediately uptake in the right parieto-occipital area. A four- after a seizure, he performed a crossing-out task, vessel cerebral angiogram revealed evidence of and he failed to cross out two of the 12 marks. The luxury perfusion in this same area. Computed two he missed were on the left side. During an tomography of the brain did not reveal any interictal interval he took the same test and crossed abnormality. out all lines. The extinction and allaesthetic We had difficulty controlling the patient's partial on October 1, 2021 by phenomena disappeared with cessation of the electro- seizures with diphenylhydantoin, and he required graphic seizure. Immediately postictally, however, he subsequent addition of phenobarbitone and carba- was momentarily mildly hypokinetic with a blunted mazepine; the three medications controlled the affect. seizures. On the third seizure-free day and two days Other pertinent laboratory values included a before discharge, he was again tested for hemispatial J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.43.11.1035 on 1 November 1980. Downloaded from

1038 Kenneth M Heilman and Gregory J Howell neglect at a time when the visual fields were normal. cells was responsible for th-e manifestations of The line bisection and crossing-out tasks were cor- inattention. Although we consider both allaes- rectly performed. He could correctly number a clock, thesia and extinction as manifestations of draw an entire daisy, and draw a cube. Mapping was inattention, these are different behaviours; con- improved. sequently, the brain mechanisms underlying these behaviours must differ. The difference under- Discussion lying these behaviours is possibly related to how other portions of the brain respond while the This patient manifested many symptoms of the attentional cells are improperly functioning. neglect syndrome during and after a focal seizure. When patients with a stable lesion, such as During a seizure he had allaesthesia to left-side cerebral infarction, recover from neglect, they tactile stimulation, and left-side extinction to go from a stage in which they are inattentive to bilateral auditory and tactile stimuli. During a unilateral stimuli or have allaesthetic responses, seizure, however, when asked to bisect a line, he to a stage in which they can detect and correctly tended to bisect the line farther to the left than lateralise unilateral stimuli but neglect contra- the left edge of the paper. lesion stimuli with bilateral simultaneous stimu- We assess patients with by lation.' 4Although while having a seizure, this holding a card in front of them and centring it patient neglected all the auditory and tactile at the midline of their body. We then ask them stimuli delivered *to the left during bilateral to close their eyes and to touch the card directly simultaneous stimulation, when undergoing uni- opposite their midline. Patients with left hemi- lateral stimulation he made no errors in the spatial neglect often point to the right of mid- auditory modality but did make allaesthetic errors guest. Protected by copyright. line. We have never seen a patient who has in the tactile modality. We have noted a similar pointed beyond the left edge of the sheet. We pattern in other patients with neglect. Inattention, therefore cannot attribute this man's intention allaesthesia, and extinction of somaesthetic and to bisect the line beyond the left of the card visual stimuli are more severe and recover more during a seizure to a decrease in visual acuity slowly than these symptoms in the auditory during the seizure. Immediately postictally he modality. We are not certain why this happens. again incorrectly bisected the line but this time Although the has stronger toward the right of midline; his interictal per- contralateral than ipsilateral projections, the formance was also to the right but was more auditory system has more ipsilateral hemispheric accurate. afferents than do either the somaesthetic or the The seizure focus appeared to be emanating visual systems. It is also possible that there are from the right parietal lobe. The importance of parietal "attention cells" similar to those de- the parietal lobe in attentional processes can be scribed by Lynch et al,8 which "attend" to inferred not only from ablation studies in man auditory stimuli. Based on our observation, we and monkeys5 but also from intracellular record- would suspect that unlike the visual attention ing in performing animals. Yin and Mountcastle7 cells, which are activated by visual stimuli mainly and Lynch et al,8 using single cortical cell record- in the contralateral visual half field, these audi- ings, identified in the parietal lobe a class of tory cells would be more likely to be activated neurons that had large receptive fields and were by ipsilateral stimuli. activated by light presented in the contralateral Pribram and McGuiness" proposed that was a half field. There subclass of cells that attention-arousal, which is concerned with http://jnnp.bmj.com/ enhanced their firing if the stimulus was signifi- stimulus reception, and intention, which is a cant and was followed by movement. The parietal readiness or preparation for action, were inde- "attentional" cells that these workers7 8 described pendent but interrelated processes. After train- performed a function similar to that which ing animals to move an extremity contralateral Sokolov9 proposed for his cortical comparator to a stimulus, Watson et al"2 induced neglect neurons. Robinson et al'0 also demonstrated the with dorsolateral frontal and intralaminar thal- presence of attentional cells in the parietal lobes. amic lesions. When stimulated on the side contra- not These cells only responded to significant lateral to their lesion, the animals performed on October 1, 2021 by visual stimuli with enhanced firing but also normally; but when stimulated on the non- responded to somaesthetic stimuli. neglected side (ipsilateral to the lesion), they It appears that during our patient's seizures failed to use the extremity opposite the lesion these attentional cells could not function as com- despite normal strength. Valenstein, Van Den parators and that dysfunction of these attentional Abell, and Heilman13 have found a similar J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.43.11.1035 on 1 November 1980. Downloaded from

Seizure-induced neglect 1039 phenomenon in animals with parietotemporal bisect lines incorrectly because hemianopia or lesions. sensory hemiinattention prevents them from see Heilman and Valenstein5 proposed that the ing how far the line extends to the left, a strategy unilateral hypokinesia may not be limited to the that ensures their seeing the left side of the line extremity contralateral to the lesion but is a in their normal field should improve perform- hypokinesia to any stimulus that comes to the ance. If patients have hemispatial hypokinesia, hypoaroused and hypoactivated hemisphere. In moving the line toward the normal half of body the case of hemispatial neglect, Heilman and space should improve performance. Valenstein5 proposed that each hemisphere is Heilman and Valenstein5 tested patients with responsible not only for mediating movements hemispatial neglect by requiring them to identify of the contralateral extremity and processing a letter at either the right or the left end of a contralateral sensory input, but also for mediat- line before bisecting that line. The task was given ing behaviour in the contralateral spatial field with the lines placed at either the right, the independent of which extremity is used. This centre, or the left of the body midline. hemispatial hypokinesia may not be limited Performance in trials when subjects were re- to the extremities but may also include eye quired to look to the left before bisecting a line movements. did not differ from when they were required to Studies of normal subjects support the hypo- look right. Performance was significantly better thesis that each hemisphere is important for when the line was placed to the right side of the mediating behaviour in the contralateral spatial body than to the left. These observations support field. The time taken to react to a lateralised the hypothesis that patients with hemispatial visual stimulus is determined by the anatomical neglect have hemispatial hypokinesia. guest. Protected by copyright. connections between the receiving hemiretina Although the results of this study are com- and the responding hand. Ipsilateral responses, patible with the hemispatial hypokinesia hypo- which are mediated by intrahemispheric neuronal thesis, there is an alternative explanation. William circuits, are faster than contralateral responses, James'" noted that "an object once attended which require interhemispheric transfer.14 For will remain in the memory whilst one inatten- example, if a stimulus is presented to the right tively allowed to pass will leave no trace behind." visual field, the response is faster with the right Although our subjects saw the full extent of the hand than with the left. This is no longer the line, it is possible that the side of the line in 'case in choice reaction times w,hen the arms are the left hemispatial field did not form a stable crossed so that the right hand is on the left side trace. As the subject explored the remainder of of the body and the left hand is on the right side. the line, he "forgot" the left side of the line and In this situation, stimuli in the right visual field performed as if he had not seen it. The hemi- for example are responded to faster with the left spatial field is not the same as the visual field hand than with the right. but refers to the space to one side of the midline This phenomenon has been termed "stimulus of the body. If there were an attentional hemi- response compatibility"'15 and has been thought spatial memory defect, it would not be for the to reflect a natural tendency to respond with the portion of the line in the left visual field but hand that is already in the appropriate hemi- rather for the portion of the line on the left spatial field. An alternative explanation is that side of the body. Unfortunately, Heilman and not for experimental paradigm could not each hemisphere is responsible only Valenstein's5 http://jnnp.bmj.com/ moving the contralateral extremity and process- distinguish between the hemispatial hypokinesia ing contralateral stimuli but also for mediating and hemispatial inattention-memory hypotheses; behaviour in the contralateral hemispatial field, however, if one accepts the latter hypothesis, it regardless of which extremity is being used. The is difficult to explain why patients with hemi- right hand, for example, takes longer to respond spatial neglect draw half a daisy when a spon- to a right-sided stimulus when it is in the left taneously drawn daisy requires no afferent input. hemispatial field than when it is in the right Because attention and intention are closely the former underlying in- hemispatial field. T,his is because, in linked, the brain mechanisms on October 1, 2021 by instance, bilateral hemispheric processing is re- tention are not well known. In man, disease of quired: the left hemisphere must process the the basal ganglia and frontal lobes may induce visual stimulus, but the right hemisphere must defects that are predominantly intentional. contribute to the response of the right hand Although the inferior parietal lobe has direct because it is in the left hemispatial field. projection to the frontal lobe,'7 we suspect that If patients with left-sided h,emispatial neglect the mesencephalic and thalamic reticular systems H J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.43.11.1035 on 1 November 1980. Downloaded from

1040 Kenneth M Heilmanz and Gregory J Howell and limbic systems are also important in mediat- 166-70. ing intention. In this patient the localised right 6 DeKosky ST, Heilman KM, Bowers D, parietal seizure appeared to activate these inten- Valenstein E. Recognition and discrimination of tional systems, not only inducing eye and head emotional faces and pictures. Brain Lang (in press). deviation to the left but also inducing the patient 7 Yin TCT, Mountcastle VB. Visual input to the to incorrectly bisect lines to the left of the test visuomotor mechanism of the monkey's parietal sheet. Immediately after the seizure ended, the lobe. Science 1977; 197:1381-3. patient appeared to attend to contralateral 8 Lynch JC, Mountcastle VB, Talbot WH, Yin stimuli; however, he then bisected lines to the TCT. Parietal lobe mechanisms of directed right of centre. Since Todd's18 description of visual attention. J Neurophysiol 1977; 40:362-89. postictal paralysis, many other postseizure de- 9 Sokolov YN. and the Conditioned fects have been described (for example, aphasia, Reflex. Oxford: Pergamon Press, 1963. sensory loss); however, the postictal hemispatial 10 Robinson DL, Goldberg ME, Stanton GE. neglect demonstrated by this man has not been Parietal association cortex in the primate: recognised. The mechanism underlying postictal sensory mechanisms and behavioral modulations. changes has not been completely elucidated, and J Neurophysiol 1978; 41:910-32. we do not know why an intentional defect per- 11 Pribram KH, McGuinness D. Arousal activation and effort in the control of attention. Psychol sisted after the seizure terminated. However, the Rev 1975; 182:116-49. postictal hemispatial neglect in the absence of 12 Watson RT, Miller BD, Heilman KM. Non- inattention helped us to further substantiate sensory neglect. Ann Neurol 1978; 3:505-8. what was seen during the seizure-namely, that 13 Valenstein E, Van Den Abell T, Heilman KM. defects of intention and attention can be Nonsensory neglect from parietotemporal lesions guest. Protected by copyright. dissociated. in monkeys. Presented at the International Neuropsychological Society Meeting, February 2, This study was supported in part by National 1980, San Francisco, California. Institutes of Health Grant NS-12218. Dr LJ 14 Berlucchi G, Heron W, Hyman R, et al. Simple Willmore helped us with the EEG, and Mrs reaction times of ipsilateral and contralateral Alice W Cu'llu provided editorial assistance. hand to lateralized visual stimuli. Brain 1971; 94:419-30. References 15 Anzola GP, Bertoloni A, Buchtel HA, et al. Spatial compatibility and anatomical factors in 1 Critchley M. The Parietal Lobes. New York: simple and choice reaction time. Neuro- Hafner Press, 1966. psychologia 1977; 15:295-302. 2 Obersteiner H. On -a peculiar sensory 16 James W. The Principles of Psychology, vol 2. disorder. Brain 1882; 4:153-63. New York: Holt, 1890. 3 Heilman KM, Watson RT. Mechanism under- 17 Pandya DM, Kuypers HGJM. Cortico-cortical lying the unilateral neglect syndrome. Adv connections in the rhesus monkey. Brain Res Neurol 1977; 18:93-106. 1969; 13:13-36. 4 Heilman KM. Neglect and related disorders. In: 18 Todd RB. Clinical Lectures on Paralysis, Disease Heilman KM, Valenstein E, eds. Clinical Neuro- of the Brain and Other Affections of the psychology. New York: Oxford University Press, . Philadelphia, 1855. Cited by 1979; 268-307. Meyer JS, Portnoy HD. Post-epileptic paralysis. 5 Heilman KM, Valenstein E. Mechanisms under- A clinical and experimental study. Brain 1959;

lying hemispatial neglect. Ann Neurol 1979; 5: 82:162-85. http://jnnp.bmj.com/ on October 1, 2021 by