0148-396 X/86/1806-0787$02.00/0 NEUROSURGERY Copyright ¢ 1986 by the Congress of Neurological Surgeons Vol. 18, No. 6, 1986 Printed in U.S.A. Hyperglycemia-induced Hemichoreoathetosis: The Presenting Manifestation of a Vascular Malformation of the Lenticular Nucleus Frederick M. Vincent, M.D. Neurology Section, Department of Medicine, Michigan State University, East Lansing, Michigan A 72-year-old diabetic woman developed paroxysmal hemichoreoathetosis during an episode of nonketotic hypergly- cemia. The movement disorder abated as the blood glucose normalized. A computed tomographic scan revealed a vascular malformation involving the lenticular nucleus on the side contralateral to the dyskinesia. Hyperglycemia has rarely been reported to cause episodic dyskinesias, but there have been no prior reports of patients with striatal vascular abnormalities in whom hyperglycemia seemingly caused a transient movement disorder. (Neurosurgery 18:787-790, 1986) Key words: Arteriovenous malformation, Athetosis, Basal ganglia, Cerebral angiography, Chorea, Hyperglycemia, Movement disorder Nonketotic hyperglycemia has rarely been reported to cause transient dyskinesias (2, 18). Likewise, arteriovenous malfor- mations (AVM) of the basal ganglia are uncommon and have infrequently been implicated as a cause of movement disor- ders (3, 7, 12, 15, 16, 19). We report the case of a diabetic woman who developed sudden left-sided choreoathetosis as- sociated with nonketotic hyperglycemia. The dyskinesias ceased as she became normoglycemic, and computed tomo- graphic (CT) scanning and cerebral angiography revealed a vascular malformation of the right lenticular nucleus. CASE REPORT A 72-year-old woman with an 8-year history of insulin- requiring diabetes mellitus suddenly developed abnormal movements of the left arm in November 1981. These move- ments increased over the ensuing 3 hours and involved the left leg and face in addition to the arm. She sought medical attention when the movements did not spontaneously cease. She denied any prior history of abnormal movements, and there was no family history of movement disorders. She was receiving no medications other than the insulin and had never used psychotropic medications. She denied visual complaints, memory dysfunction, weakness, or sensory loss. She specifi- cally denied a prior history of rheumatic chorea or chorea gravidarum. Her general medical examination, including vital signs, was normal. She was alert and oriented with normal mentation. Speech was clear. with intact comprehension and repetition. Cranial nerve examination was normal. Choreic movements of the left arm and leg. and to a lesser degree the face, were associated with intermittent distal athetotic movements, and at times the left arm was held in a dystonic posture. Voluntary movement did not increase or diminish the dyskinesias. There were no abnormal movements on the right. Muscle tone was normal, and there was no obvious weakness. Deep tendon reflexes were | on the right and 1+ on the left. and there was no Babinski response. Primary and cortical sensory modalities were normal. The carotid arteries were without bruits. The blood glucose level was 501 mg/dl, and ketones were absent. The sodium value was 138, the potassium value was 4.0, and the blood urea nitrogen was 20 mg/dl. Liver function tests. 787 complete blood count, antinuclear antibody test, VDRL, calcium and phosphorous levels, and a sedimentation rate were all normal. The calculated serum osmolarity was 329 milliosmoles/litre. The patient was treated with insulin and fluids, and 8 hours later the movements had ceased. Exami- nation at this time was normal except for slight dystonic posturing of the left arm when walking: blood glucose level was 125 mg/dl at this time. CT scan revealed an enhancing lesion of the right lenticular nucleus (Fig. 1); no other abnor- malities were present. Cerebral arteriography revealed that the right carotid artery was normal without evidence of ath- erosclerosis. A faint blush was evident in the area of the lateral globus pallidus-putamen complex on the right (Fig. 2); the intramedullary vein lateral and superior to the blush was prominent and joined the thalamostriate vein. Arteriovenous shunting was present with early filling of the thalamostriate vein and internal cerebral vein on the right. The lenticulostri- ate arteries were prominent and supplied the vascular malfor- mation, which appeared to be predominantly of venous ori- gin. The patient was discharged from the hospital after 4 days of confinement because the dyskinesias did not reappear. The patient has remained neurologically asymptomatic for 4 years. Her diabetes has remained under good control, and the blood sugar level has remained below 250 mg/dl. A CT scan with contrast in July 1985 was unchanged from the one performed in November 1981; it demonstrated persistence of the en- hancement (Fig. 3). DISCUSSION Neurological abnormalities are common in nonketotic hy- perglycemia and may include delirium or coma, in addition to more focal neurological changes (10. 20). The focal signs include aphasia, hemiparesis, hemisensory deficits, tonic ocu- lar deviation, and focal or generalized seizures (10. 20). Con- tinuous focal epilepsy (epilepsia partialis continua) is known to complicate nonketotic hyperglycemia. These seizures may occur when the limb is at rest or, more rarely, may be movement-induced. The typical movement-induced seizure is tonic and triggered by movement of the involved limb; electroencephalographic (EEG) manifestations of the seizures are often absent (1. 20). Less commonly, the movement- 788 VINCENT Neurosurgery, Vol. 18, No. 6 Fic. 1. CT (November 1981) reveals an ill-defined density in the right lenticular nucleus on the unenhanced scan (A) that enhances after the administration of contrast agent (B). The patient’s right side is to the viewer's right. induced seizure is of the tonic-clonic type occurring after sustained repetitive movement of the limb; focal EEG abnor- malities are commonly observed (1). In contrast to the non- ketotic hyperglycemic states, neurological abnormalities other than depression of the level of consciousness are uncommon in diabetic ketoacidosis (10). There have been only two reports dealing with hypergly- cemia-induced dyskinesias (2, 18). In 1960, Bedwell (2) re- ported a hypertensive patient who at age 60 developed “con- tinuous facial grimacing and wild involuntary movements of the face, neck, and extremities” on the right, associated with a blood sugar of 450 mg/100 ml. The movements gradually diminished over a 4-week period as the blood sugar level normalized; on discharge from the hospital, minimal cho- reoathetotic movements persisted. Over the ensuing | years, this patient had at least two exacerbations of the movement disorder, each associated with hyperglycemia. At the time of her last evaluation, she had a mild left hemiparesis, bilateral choreoathetotic movements of the hands, and bilateral “facial grimaces.” Lacking pathological confirmation, one can only speculate on the etiology of this patient’s movement disorder. It is quite likely that the persistent dyskinesias were the result of infarction of subcortical structures. This patient did not have reversible hyperglycemia-induced dyskinesias; however, her case illustrates how hyperglycemia may exacerbate a persistent movement disorder. Goldblatt et al. (9) reported a patient in whom two distinct episodes of severe left-sided hemichorea were associated with two separate right-sided cerebral lesions, one in the putamen and the second in the caudate nucleus, as confirmed at necropsy. This patient was hyperglycemic through part of her hospital stay, but the authors state that they could not correlate her dyskinesias with a rise in the blood glucose level. Episodic dyskinesias have also been reported as a manifestation of cerebral ische- mia (13), with the movements lasting from minutes to an hour. Kase et al. (11) recently reported a hypertensive patient with acute hemichorea-hemiballismus associated with a la- cunar infarct documented by CT in the contralateral putamen and caudate nuclei. Rector and associates (18) reported three patients with nonketotic hyperglycemia and transient hemichorea with nor- mal CT scans of the head. Their blood sugar levels ranged from 456 to 1000 mg/dl; serum osmolarity ranged from 303 to 331 milliosmoles/litre. The dyskinesias were focal in all three patients and lasted from 18 to 24 hours; as the blood glucose normalized, the movements ceased. These patients are clearly different from the one reported by Bedwell (2) because their dyskinesias were truly transient. Thus, dyski- nesias secondary to hyperglycemia last hours and not days or weeks and are not persistent following the correction of the hyperglycemia, unless there is underlying central nervous system pathology. Vascular malformations in the region of the basal ganglia are uncommon. In the series of 110 AVMs reported by Paterson and McKissock (16), only 8% were located in the basal ganglia, and 5.7% of the series of AVMs from the Lahey Clinic were in this area (15). Extrapyramidal dysfunction secondary to an AVM is quite rare, with only eight cases having been reported (Table |). The precise pathophysiologi- cal mechanisms involved in the production of extrapyramidal movements from AVM’s are not known, but the postulated mechanisms are shunting of blood through the AVM with a vascular steal occurring from the normal brain tissue, mass effect upon the basal ganglia by the AVM itself or by a hematoma, or abnormalities of neural tissue development associated with the abnormal blood vessel development (7). Chorea and athetosis are movements that may arise from dysfunction within the basal ganglia. Carpenter (4) reviewed the reports of 32 patients with hemiathetosis, 22 had lesions involving the lenticular nucleus. Huntington’s disease is as- sociated with chorea and caudate atrophy and depletion of gamma aminobutyric acid (GABA) has been found in the June 1986 Fic. 2. Anteroposterior view of the intracranial branches of the right internal carotid artery reveals a lens-shaped vascular malfor- mation (arrows) in the area of the lateral globus pallidus and the putamen. brains of patients with this disorder, implicating GABA defi- ciency as a possible cause of the choreic movements (17). There is a significant relationship between the subthalamic nucleus, globus pallidus, and substantia nigra (3). The sub- thalamic nucleus has inhibitory influences on the globus pallidus mediated by GABA and dopamine-containing pro- jections (3, 6). GABA is found in highest concentration in the globus pallidus, substantia nigra, and hypothalamus, with an intermediate concentration occurring in the caudate and pu- tamen (5). That GABA is involved in the production of dyskinesias has been demonstrated in the monkey by the studies of Crossman et al. (6), who were attempting to identify the site of action of GABA antagonists in the production of experimental hemiballismus. Stereotactic injection of the GABA antagonist picrotoxin near the lateral segment of the globus pallidus gave rise to a hyperkinetic disorder of both contralateral limbs. These movements resembled the dyski- nesias elicited by similar injections into the subthalamic nu- cleus (hemichorea that resembled hemiballismus); however, a marked difference was the production of a prominent athetoid component to the movement in the upper extremities. The injection of picrotoxin into the dorsomedial putamen induced myoclonic movements of the neck musculature and the con- HYPERGLYCEMIA-INDUCED HEMICHOREOATHETOSIS 789 Fic. 3. CT with contrast (July 1985) demonstrates the enhancing area in the right lenticular nucleus, which is unchanged from the previous scan of November 1981. The patient’s right side is to the viewer's right. tralateral upper limb. The injection of the GABA agonist muscimol was without effect at the sites where GABA antag- onists induced dyskinesias. Thus it would seem that localized deficiencies of GABA in the basal ganglia or related nuclei are in part responsible for the appearance of dyskinesias. Nonketotic hyperglycemia and ketoacidosis may cause a depression of the Kreb’s cycle (10, 20). In these conditions, the energy requirements of brain tissue will be met by in- creased metabolism of ketone bodies during ketoacidosis or amino acids (e.g., GABA or L-glutamic acid) (10, 20). GABA may be metabolized in the brain via the GABA shunt, which represents an alternate pathway to a portion of the Kreb’s cycle (3). The GABA shunt may provide 10 to 40% of the energy requirement of neural tissue, and the increased rate of utilization of GABA in the presence of a reduced rate of activity of the Kreb’s cycle may result in a deficiency of GABA that could cause abnormal movements in addition to seizures (10, 20). Overall, the net result in nonketotic hyper- glycemia is a lowering of the GABA level, reducing the threshold for seizures and increasing the likelihood of dyski- nesias. Hyperglycemia also produces a global decrease in regional cerebral blood flow (CBF) with maximal reduction in the globus pallidus, and it enhances the development of brain injury by ischemia (8, 14). Thus, in the presence of hyperglycemia, the reduction of CBF, possibly more so in the pallidum, may contribute to focal ischemia and reduction of local amounts of GABA. Choreoathetosis or hemiballismus may be the initial signs of nonketotic hyperglycemia, and they should be expected to disappear as the blood glucose level is brought to normal levels. It is possible that underlying focal cerebrovascular disease provides the base for the metabolic changes that may result in depletion of neurotransmitters, particularly GABA. A serum glucose level should be determined in any patient with the new onset of ballism or choreoathetosis, and a CT scan should be performed to exclude vascular disease of the basal ganglia. 790 VINCENT TABLE | Neurosurgery, Vol. 18, No. 6 Extrapyramidal Dysfunction Due to Cerebrovascular Malformations* Type and Site Author (Ref.)/Year Age* Type of Movement SAH of Malformation Treatment Follow-up Paterson & McKissock NR_ Athetosis of hemiparetic NR = AVM “central” NR NR (16)/1956 limbs Shaw (19)/1972 19 L spasmodic torticollis AVM fed by hyper- NR NR trophied R MCA Lobo-Antunes et al. (12)/ 1974 Case | 1 Rarm tremor & dys- AVM L thalamus, Radiation Movements ceased after tonia BG first SAH Case 2 NR __ L torticollis AVM R posterior NR 9 yr after SAH without thalamus symptoms/signs Case 3 19 Retrocollis AYM R parietal lobe — Section of C-3- Slight improvement C-5 nerve roots Case 4 9 ~ Larm tremor - AVM R thalamus, Embolization x2 No improvement BG Diamond et al. 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