Epiiepsiu, 32(2):221-224, 1991 Raven Press, Ltd., New York Q International League Against Epilepsy

Gaze-Evoked Visual Seizures in Nonketotic Hyperglycemia Max B. Duncan, Bahman Jabbari, and Michael L. Rosenberg Sections of Neurophysiology and Neuroophthalmology, The Neurology Service, Walter Reed Army Medical Center, Washington, D.C., and The Uniformed Services, University of the Health Sciences, Bethesda, Maryland, U.S.A.

Summary: Focal motor seizures are commonly a symptom of nonketotic hyperglycemia (NKH). Postureinduced motor seizures are less common but have been reported in some patients with this disorder. We report the first case of gaze-evoked sensory (visual) seizures in

nonketotic hyperglycemia. Both seizures and ictal EEG findings disappeared shortly after hyperglycemia was corrected. Key Words: Nonketotic hyperglycemia-Epileptic seizures-Reflex epilepsy.

Nonketotic hyperglycemia (NKH) is a syndrome comprising severe hyperglycemia, hyperosmolality , and intracellular dehydration with little or no ketoacidosis (Di Benedetto et al., 1965). Polydipsia, polyuria, and weight loss are the most common constitutional symptoms. In most patients with NKH, consciousness is not severely depressed, particularly if the patient remains well hydrated (Stahlman et al., 1988). Neurologic manifestations, particularly seizures, may provide the first clinical clues to the presence of NKH. Focal motor seizures are the most common type (Daniels et al., 1969), although generalized, tonic-chic seizures also occur (Stahlman et al., 1988). Rarely, patients with NKH are reported to have reflex or posture-induced focal motor seizures, defined as seizures induced by movement or posturing of a body part (Brick et al., 1989). We report the first patient with NKH in whom simple partial visual seizures were consistently evoked by gazing to the left.

for the past week and were described as a right temporooccipital, throbbing pain, unassociated with nausea or vomiting. The visual symptoms could be consistently elicited by looking to the left and would not occur under any other circumstances. Past medical history was essentially unremarkable. She had no history of migraine, epilepsy, or other neurologic disorders. General physical examination showed an alert, fully oriented, obese woman who was in no acute distress but whose blood pressure was 1504 10. Neurologic examination was normal except for a left homonymus hemianopia. Asking the patient to look to the left consistently produced stereotypic visual experiences. After gazing left 2-3 s she perceived a small, luminous ball in her left visual hemifield, which enlarged like a “bright sun” and enveloped the entire hemifield for 1-2 s. She would then visualize (on the left) formed objects, such as articles of furniture and unfamiliar human faces. These episodes could be reproduced every 5-10 min. Concurrent EEG recording showed rhythmic right temporooccipital discharges, timelocked to the visual images (Figs. 1 and 2). Routine blood work, including hemogram, erythrocyte sedimentation rate, and electrolytes were normal, but serum glucose was 27.7 mM (499 mgl dl), and osmolality was 308.1 mosmil. The urine was negative for ketones, but showed 3 + glucose. Electrocardiogram disclosed no abnormalities. Both computed tomography and magnetic resonance imaging studies of the head were normal.

CASE REPORT

A 43-year-old black woman examined in the emergency room complained of headaches and “flashing lights” in her left visual field. The headaches had been occurring two to three times daily Received January 1990; revision accepted April 1990. Address correspondence and reprint requests to Dr. B. Jabbari at Neurology Service, Ward 62, Walter Reed Army Medical Center, Washington, D.C. 20307-5001, U.S.A.

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The patient’s metabolic picture was believed to be consistent with NKH; she was treated with insulin and hypotonic saline. Within 48 h, all visual symptoms had disappeared; the left homonymus hemianopsia resolved totally. The patient remained asymptomatic during a 6-month follow-up period, and EEG became normal.

DISCUSSION Seizures as a manifestation of NKH have been documented in the medical literature (Maccario et al., 1968). Focal motor seizures and epilepsia parof cases of tialis continua (EPC) occur in ~ 1 9 % NKH and tend to be an early sign (Singh et al., 1980). Posture-induced seizures have been reported less frequently but appear to be specific for NKH (Brick et al., 1989). Table 1 shows previously reported cases of movement or posture-induced seizures in NKH. All patients were aged >40 years, and most had seizures as the initial manifestation of the metabolic disorder. In 9 of 12 patients, focal motor seizures were produced by voluntary movement of an involved limb. Seizures were induced in the other three patients by head and/or eye deviation. Effective therapy consisted of correction of the metabolic disorder, rather than administration of antiepileptic medications. Seizures with NKH may be triggered by either peripheral or central mechanisms. Gabor (1974) reported a 49-year-old patient in NKH in whom grasping movements of the left hand produced focal

seizures manifested by left carpopedal spasm. Simultaneous EEG recording showed rhythmic right hemispheric spike activity. Despite a left brachial plexus block (induced by local anesthesia), attempted movement of the paretic limb still yielded rhythmic spike activity. This result demonstrates the importance of central mechanisms in this syndrome. Exactly how the metabolic aberrations of NKH result in focal seizures is unclear, although hyperosmolality certainly plays a role. Hyperglycemia of sufficient degree sets up an osmotic gradient between the extracellular and intracellular compartments of the brain, leading to intracellular dehydration and dysfunction (Maccario, 1968). If small, preexisting cortical lesions were exposed to these conditions, focal seizures could result (Singh et al., 1980). Such foci have been hypothesized to be present in diabetic patients with cerebral areas of borderline vascular supply (Maccario, 1968). Vastola et al. (1967), using a penicillin-induced spike focus in cats, demonstrated that hypertonic glucose and mannitol increased the frequency of electrical seizures in striate cortex. An alternate hypothesis is that hyperglycemia and hyperosmolality induce focal cortical venous sludging or thrombosis; such foci could be highly epileptogenic (Venna, 1981). Another metabolic aberration in NKH is depression of the Krebs cycle, which decreases brain .glucose utilization. As compensation, y-aminobutyric acid (GABA) may be metabolized to succinic acid through the succinic semialdehyde pathway (GABA shunt). This pathway supplies S40% of the energy

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Epilepsia, Vol. 32, No. 2 , 1991

GAZE-EVOKED VISUAL SEIZURES

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TABLE 1. Cases of rejlex epilepsy associated with nonketotic hyperglycemia Reference

Age (yr)/sex

Triggering movement

Seizure

EEG findings

Ocular clonus, dysarthria, anomia L carpopedal spasm

4-Hz spike and wave, L hemisphere 12-Hz rhythmic spikes, R centroparietal region L frontal sharplslow paroxysms 4-Hz spike and wave, L hemisphere None reported None reported

Stahlman et al., 1988

74/M

Deviation of head, eye R

Gabor, 1974

49/F

Grasping with L hand

Venna and Sabin, 1981

581F

R arm clonus

Brick et al., 1989

661M

Voluntary movements, R arm Deviation of headieyes R

Brick et al., 1989 Brick et al., 1989

60/M 54/F

L hand jerking Jerking R armileg

Brick et al., 1989

61/M

Active elevation, L arm Passive/active elevation of R armfleg L arm movement

Brick et al., 1989

65/F

Aquino and Gabor, 1980

65/M

Passiveiactive elevation of R arm R arm movement

R wrist clonus, altered consciousness R arm jerking

Aquino and Gabor, 1980

59/F

Neufeld et al., 1988

73fM

R orbicularis myoclonus, spread to R face/arm Clonic tongue movements

Present study

43/F

Voluntary lid elevation, flex/extend R arm Elevation of L arm and rubbing of scalp Voluntary leftward gaze

requirement of nervous tissue under these conditions. GABA is known to be an inhibitory neurotransmitter in the central nervous system. GABA catabolism would be expected to lower the seizure activity threshold in NKH (Guisado, 1975) and indeed ketosis inhibits the paroxysmal activity induced by hyperosmolar states; seizures are rare in patients with diabetic ketoacidosis. GABA would be conserved under these conditions because brain energy could be derived from ketone bodies (Singh, 1980). Why reflex seizures occur in NKH and not in other metabolic disorders is not clear. The neuronal response to afferent stimuli may be more sensitive to glucose than other factors. Hyperglycemia could then result in abnormal discharges in response to a variety of peripheral inputs (e.g., proprioceptive). Our patient’s clinical presentation offers a limited differential diagnosis. Migraine often produces visual symptoms, but migraine appears unlikely because both visual experiences and EEG findings disappeared soon after hyperglycemia was corrected. As shown in Table 1 , various ictal EEG abnormalities have been reported in NKH seizures. Although our patient’s EEG findings are similar to those already described, the “triggering movement” to induce the seizures and the nature of the ictal events differ. Only one previous case, that of Brick et al. (I989), had a similar triggering movement. In this patient, focal seizures were produced by deviation of the head and eyes to the right; however, the ictus consisted of jerking of the eyes and language difficulties, not sensory experiences.

Ocular clonus, anomia

L handfarm jerking

Formed/unformed visual images

2- to 3-Hz, rhythmic activity, R hemisphere Bifrontal sharp waves 6- to 7-Hz spike and wave complexes 1-Hz spike and wave L frontal region 3- to 5-Hz sharp activity, R frontocentral Rhythmic discharges R temporooccipital region

In humans, bilateral occipital or parietooccipital lesions cause abnormalities of pursuit movements (Rizzo and Hurtig, 1989; Atkinson, 1984); unilateral, acquired occipital lesions do not interfere with pursuits or saccades. Neither did our patient, with a presumed disturbance of the right temporooccipital cortex, demonstrate impairment of pursuit or saccaddic eye movements. Her visual hallucinations were confined to the left hemifield and were persistently evoked by gazing to the left. Sharpe and Deck (1978) showed that the middle temporal gyrus of the macaque monkey contains cells that discharge in relation to target movements. In humans, this area corresponds with Flechsig’s area 10, located at the temporooccipital junction (Allman et al., 1981). Furthermore, saccades toward a laterally placed object, or merely visual attention to such objects, can produce discharges in posterior parietal neurons (Yin and Mountcastle, 1978; Bushnell et al., 1981). Thus, we postulate that in our patient gaze to the left produced abnormal discharges in right peristriate cortical neurons, leading to visual hallucinations. The present case is the first reported case to consist of strictly sensory, as opposed to focal motor, phenomena. Recognition of reflex sensory seizures in NKH is important, because it can be the initial symptom of a treatable metabolic disorder.

REFERENCES Allman JM, Baker JF, Newsome WT, et al. The cortical visual areas of the owl monkey: topographic organization and funcEpilepsia, Vol. 32, N o . 2, 1991

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tional correlates. In: Wollsey CN, ed. Cortical sensory organization. Englewood Cliffs, NJ, Humana Press, 1981:171-86. Allman JM, Kass JH. A representation of the visual field in the caudal third of the middle temporal gyrus of the owl monkey. Brain Res 1971;31:85-105. Aquino A, Gabor AJ. Movement-induced seizures in nonketotic hyperglycemia. Neurology 1980;30:600-6. Brick JF, Gutrecht JA, Ringel RA. Reflex epilepsy and nonketotic hyperglycemia in the elderly: a specific neuroendocrine syndrome. Neurology 1989;39:394-9. Bushnell MC, Goldberg ME, Robinson DL. Behavioral enhancement of visual responses in monkey cerebral cortex: I. Modulation in posterior parietal cortex related to selective visual attention. J Neurophysiol 1981;46:755-72. Daniels JC, Chokroverty S, Barron KD. Anacidotic hyperglycemia and focal seizures. Arch Intern Med 1969;124:701-6. Di Benedetto RJ, Crocco JA, Soscia JL. Hyperglycemic nonketotic coma. Arch Intern Med 1965;116:74-82. Gabor AJ. Focal seizures i n d u c d by movement without sensory feedback mechanisms. Electroencephalogr Clin Neurophysiol 1974;36:40340. Guisado R, Arieff AI. Neurological manifestations of diabetic comas; correlation with biochemical alterations in the brain. Metabolism 1975 ;24:665-79. Maccario M, Messis CP, Vastola EF. Focal seizures as a manifestation of hyperglycemia. Arch Neurol 1968;19:525-34. Neufeld MY, Blumen SC, Nisipeanu P, et al. Lingual seizures. Epilepsia 1988;29:30-33. Rizzo M, Hurtig R. The effect of bilateral visual cortex lesions on the development of eye movements and perception. Neurology 1989;39:406-13. Sharpe JA, Deck JHN. Destruction of the internal sagittal stratum and normal smooth pursuit. Ann Neurol 1978;4:473-6. Singh BM, Strobos RJ. Epilepsia partialis continua associated with nonketotic hyperglycemia: clinical and biochemical profile of 21 patients. Ann Neurol 1980;8:155-60.

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Stahlman GC, Auerback PS, Strickland WG. Neurologic manifestations of nonketotic hyperglycemia. J Tenn Med Assoc 1988;8 1 :77-80. Vastola EF, Maccario M, Homan R. Activation of epileptogenic foci by hyperosmolality. Neurology 1967;17:520-6. Venna N , Sabin TD. Tonic focal seizures in nonketotic hyperglycemia of diabetes mellitus. Arch Neurol 1981 ;38:5124. Yin TCT, Mountcastle VB. Mechanisms of neural integration in the parietal lobe for visual integration. Fed Proc 1978; 37:2251-7.

RkSUME Des crises motrices focales sont un symptdme frequent de I’hyperglyckmie non cktosique. Des crises motrices induites par la posture sont moins frequentes et ont ktC rapportkes chez quelques patients prksentant cette affection. Les auteurs rapportent le premier cas de crises sensorielles (visuelles) provoqukes par la fixation dans le cadre d’une hyperglyckmie non cktosique. Les crises et les constatations EEG critiques ont disparu rapidement apres correction de I’hyperglyckmie.

(P.Genton, Marseille)

ZUSAMMENFASSUNG Ein Symptom der nicht-ketotischen Hyperglykamie sind gewohnlich fokal-motorische Anfalle. Haltungsinduzierte motorische Anfalle sind weniger haufig, wurden jedoch bei einigen Patienten mit dieser Erkrankung berichtet. Wir berichten uber den ersten Fall von durch Starren hervorgerufenen, sensorischen (visuellen) Anfallen bei nichtketotischer Hyperglykamie. Sowohl Anfalle als auch iktale EEG-Befunde verschwanden kurz nach Besserung der Hyperglykamie. (C. Benninger, Heidelberg)