Case Reports

123I-iodoamphetamine SPECT Brain Imaging in Alternating Hemiplegia Mary L. Zupanc, MD*, Jeff A. Dobkin, MDt, and Scott B. Perlman, MDt

Alternating hemiplegia of childhood is an unusual dis- order characterized by early onset (occurring before 18 months of age); repeated attacks of hemiplegia involv- ing both sides of the body; other paroxysmal phe- nomena, such as tonic stiffening, dystonic posturing, choreoathetoid movements, ocular motor abnormal- ities, and autonomic disturbances, in association with bouts of hemiplegia or occurring independently; and evidence of mental or neurologic deficits. A girl was examined because of left hemiplegia at the age of 16 months. The patient had begun exhibiting episodes of alternating hemiplegia at approximately 4 months of age. They consisted of tonic stiffening and dystonia of the right or left extremities, lasting from 30 min to several hours and followed by residual hemiparesis. They were invariably accompanied by ocular motor abnormalities. Magnetic resonance imaging, computed tomtlgraphy, and angiography all were normal. Single proton emission computed tomography brain images dur ing an acute episode of right hemiplegia dem- onstrated hypoperfusion of the left cerebral hemi- sphere. Following improvement of the hemiplegia, the patient was re-evaluated. The uptake of the radiotracer in the left hemisphere was increased. The scan did not demonstrate significant asymmetry in cerebral perfusion.

Zupanc ML, Dobkin JA, Perlman SB. 123I-iodoampheta- mine SPECT brain imaging in alternating hemiplegia. Pediatr Neurol 1991 ;7:35-8.

Introduction

Alternating hemiplegia of infancy was initially de- scribed by Verret and Steele in 1971 [1 ]. Several additional case reports soon followed [2-5],

In 1980, Aicardi and Krageloh described 5 new cases and delineated the pertinent clinical features, including the following [6]:

(1) Early onset (before 18 months of age); (2) Repeated attacks of hemiplegia involving both sides

of the body; (3) Other paroxysmal phenomena, such as tonic stiffen-

ing, dystonic posturing, choreoathetoid movements, ocular motor abnormalities, and autonomic disturbances, in asso- ciation with hemiplegia or occurring independently; and,

(4) Evidence of cognitive or neurologic deficits. The pathophysiology of alternating hemiplegia is not

clearly understood. Many authors have hypothesized that alternating hemiplegia is related to migraine because of its paroxysmal nature and clinical similarity to hemiplegic (complicated) migraine headaches. Aicardi and Krageloh suggested that the clinical factors of alternating hemiplegia resemble those of basilar migraine with vascular distur- bances of the brainstem [6]; however, unlike migraine headaches, the family history usually is unremarkable. In addition, structural abnormalities of the cerebral cortex must occur because of the frequency of accompanying cognitive and other longstanding neurologic deficits. It is possible that alternating hemiplegia is a manifestation of an atypical type of epilepsy; however, the lack of epilepti- form discharges on electroencephalography (EEG) ob- tained during these attacks argues against this mechanism.

Our patient's course is consistent with the features of alternating hemiplegia, as discussed by Aicardi and Krageloh [6].

Case Report

This patient was born weighing 3,300 gm at term after a normal pregnancy, labor, and delivery. There were no pefinatal problems. At the age of 4 months, she had a prolonged generalized tonic-elonic seizure several hours after her second DTP immunization. After pheno- barbital was administered, the seizures ceased. EEG, which was per- formed soon after this event, revealed left focal slowing. Enhanced and unenhanced computed tomography (CT), routine laboratory studies, and lumbar puncture were normal. The patient continued to receive phenobarbital.

At the age of 5 months, she experienced a prolonged episode of hemiplegic tonic stiffening; repeat EEG was normal. The phenoba~ital dosage was increased; however, she continued to have these prolonged episodes, consisting of movement of the head and eyes, either to the right or to the left, accompanied by tonic stiffening of the ipsilateral extremities. The duration of episodes ranged from 30 rain to several

From the *Department of Neurology; University of Wisconsin Hospitals; and tDepartment of Nuclear Medicine; University of Wisconsin Hospitals and Clinics, and William S. Middleton Memorial Veterans Hospital; Madison, Wisconsin.

Communications should be eddmssed to: Dr. Zupanc; University of Wisconsin Hospitals; Department of Neurology - H6/560; 600 Highland Avenue; Madison, WI 53792. Received March 27, 1990; accepted August 13, 1990.

Zupanc et al: Alttrnating Hetm'pl~ i~5

Figure 1. (Upper 2 rows) Static SPECT images of this patient durhtg an episode of right hemiplegia. Study was pelfotwted with a GE Star 11 SPECT gamma camera equipped with a 30 ° slant hole collimator. Images were obtained 20 rain following intravenous injection of 3 mCi of I231-1MP. These images demonstrate h37Jope6fusion of the entire left cerebral hemisphere. (Lower 2 rou's) Repeat static SPECT image of this patient u'hen she was at haseline. "rite sttt(IV demonstrates no petfusion abnormalities.

hours. They were invm-iably followed by residual hemiparesis, of hours to days in duration. Subsequently. phenobarbital, phenytoin, carba- mazepine, valproate, and chlorazepate were administered. Despite anti- epileptic drug therapy, the episodes continued to {x:cur.

When first evaluated at the University of Wi,~onsin at the age of 16 months, she was developmentally delayed, and was experiencing a left- sided episode. She was awake and alert, but did not speak. Intemait- tently, the eyes deviated to the left. medially and upward, disconjugate-

ly. The remainder of tile cranial nerves were intact. Dystonia was present in the upper extremities, especially o11 the left. The lower ex- tremities were spastic. With mildly noxious stimuli, she withdrew both legs. The deep tendon reflexes were hyperreflexic and the Chaddock maneuver elicited flexor ttxz signs. She could walk only with assist~mce.

The initial evaluation included rmnnaI enhanced ;rod unenhanced CT, magnetic resonance imaging (MRI), and 4-vessel angiography. Oph-

36 PEDIATRIC NEUROLOGY Vol. 7 No. I

thalmologic examination was normal. Lumbar puncture demonstrated no cerebrospinal fluid (CSF) abnormalities. Sedimentation rate, fluores- cent antibody panel including antinuclear antibody, electrolytes, glu- cose, BUN, creatinine, calcium, magnesium, liver function tests, total protein, albumin, cholesterol, triglycerides, pyruvate, and urine metabo- lic studies for amino and organic acids were normal. Lactate was elevated at 3.3 (normal: __. 2.0). Prolonged video EEG monitoring did not capture any episodes. Again, various antiepileptic drugs were ad- ministered but without success.

One month later, at the age of 17 months, she returned to the clinic while having an episode. Her eyes were deviated tonically to the left and she had tonic stiffening of the left arm and leg. EEG was per- formed immediately and demonstrated bihemispheric slowing which was maximal over the right posterior head region. There was no epilep- tiform activity. Following this episode, she had flaccid left hemiparesis with mild choreiform movements of her extremities and dysphagia which persisted for 24-48 hours. A punch skin biopsy was performed; electron microscopic examination revealed no inclusions or other ab- normalities. CSF studies for neurotransmitter products, including 5- HIAA, HVA, and 3-MHPG were normal. A 24-hour urine collection for vanilmandelic acid, urine and serum amino acids, serum lead level, protoporphyrin screen, and serum pyruvate all were normal. Serum lac- tate was slightly elevated at 2.1. Antiepileptic medication was gradual- ly withdrawn and oral benztropine 250 lag twice-a-day was admini- stered. There were no apparent side effects and the patient demon- strated mild improvement in symptomatology.

Flunarizine, a c~lcium channel blocker, was eventually administered. It resulted in a marked reduction in the intensity and frequency of the hemiplegic episodes [7-9]. Additionally, she has made some impressive developmental gains on flunarizine, although she remains delayed. At the age of 31/2, she walks and has a vocabulary of about 50 words.

At age 17 months, the patient underwent a single proton emission computed tomography (SPECT) scan using 1231-iodoamphetamine (IMP) to further evaluate her brain perfusion. She was studied twice, once when she presented with right hemiplegia and again when she was at baseline.

All studies were performed with a GE Star II SPECT gamma camera equipped with a 30 ° slant-hole collimator. Three mCi of 123I-IMP (Medi-Physics, Inc.), produced initially by the (p,2n) and later the (p,5n) reaction, was injected into a peripheral arm vein while the patient was lying in a dark, quiet room. Sedation was accomplished by using 60 mg/kg of oral chloral hydrate. Her eyes were closed during the procedure. Data acquisition was begun 20 min after injection. Sixty-four projections at 40 sec per projection were used for data ac- quisition, yielding an average imaging time of about 40 min. Images were acquired into a 128 x 128 matrix. Reconstruction was performed with a Butterworth filter at a cutoff frequency of 0.41 and a power of 10. Linear attenuation correction was performed with a calculated value of 0.12 cm "1. Images then were analyzed qualitatively for defects in IMP uptake.

SPECT brain images obtained during the right hemiplegic episode demonstrated hypoperfusion in the left cerebral hemisphere (Fig 1 upper). She was re-examined at a later date when the hemiplegia was greatly improved. The imaging was nearly normal with the uptake of the radiotracer much improved in the left hemisphere (Fig I lower).

Discussion

Our patient presented with classic al ternat ing hemi-

plegia associated with the fol lowing: (1) Onset before 18 months of age; (2) Repeated episodes of hemiplegia involv ing both

sides of the body; (3) Other paroxysmal phenomena, particularly dystonic

pos tur ing , choreoathetoid movemen t s , and oculogyr ic movements , occurr ing in association with hemiplegia and

independent ly; and,

(4) Ev idence of base l ine cogn i t ive and neuro logic impa i rments (i.e., developmenta l delay, hyperreflexia, hypertonia).

All of her diagnostic studies were normal (i.e., metabo- lic studies, MRI, CT, angiography) except for an EEG obtained during a hemiplegic episode which demonstrated polymorphic, nonrhythmic theta and delta slowing over the contralateral hemisphere but no ongoing epileptiform activity.

SPECT brain imaging, using 123I-IMP, was performed during an episode of right hemiplegia and revealed hypo- perfusion of the entire left cerebral hemisphere. This hypo- perfusion was transient. Repeated SPECT brain imaging when the hemiplegia had resolved did not demonstrate this finding.

Previous studies recorded focal s low-wave abnormal- ities on EEG during an episode of hemiplegia [1,2]. An- giography has repeatedly failed to demonstrate structural or dynamic changes (i.e., vasospasm) in the cerebral blood vessels. Most angiographic studies have been performed when patients have no hemiplegia; however, 1 patient had right retrograde brachial angiography performed 11/2 hours fol lowing the onset of profound left hemiplegia. The result was normal [1].

To our knowledge, SPECT brain imaging of patients with alternating hemiplegia has not been reported pre- viously. In our patient, the SPECT scan clearly demon- strated transient, reversible hypoperfusion to the contralat- eral cerebral hemisphere during hemiplegia. Blood flow to the brainstem was not evaluated. The EEG finding of focal s lowing over the hypoperfused hemisphere correlates well with the SPECT scan and is suggestive of hemispheric dysfunction.

The f inding of hypoperfusion to the involved hemi- sphere suggests that this is the mechanism by which :the neurologic deficit is produced; however, it is also possi- ble that the hypoperfusion documented by the SPECT scan is the result of a series of interactions, with the more fundamental perturbation not yet identified. It is unlikely that the hypoperfusion is secondary to embolic/ thrombotie p h e n o m e n o n because the results o f the angiographic studies of these patients are normal. Vasospasm could pos- sibly be the mechanism by which the hypoperfusion is

produced. The use of 123I-IMP SPECT brain imaging in our patient

with alternating hemiplegia aided in the diagnosis and provided important pathophysiologic information about the vascular nature of this disorder. The fact that flunari- zinc, a calcium channel blocker which has been demon- strated to protect brain cells from hypoxia and prevent vasospasm, has resulted in marked improvement in ou r pat ient 's symptomatology also is supportive of under ly ing vascular instability as the mechanism of hemiplegic epi -

sodes [7-9]. Further studies with SPECT brain imaging .are needed

to document the s ignif icance of our f ind ing in pat ients with alternating hemiplegia.

Zupane etali Alternafing~Hemiple~ia ~' :

References

[1] Verret S, Steele JC. Alternating hemiplegia in childhood. Pediatrics 1971;47:675-9.

[2] Hosking GP, Cavanagh NPC, Wilson J. Altemating hemiplegia: Complicated migraine of infancy. Arch Dis Child 1978;53:656-9.

[3] Dittrich J, Havlova M, Nevsimaiova S. Paroxysmal hemiparesis in childhood. Dev Med Child Neurol 1979;21:800-6.

[4] Golden GS, French JH. Basilar artery migraine in young chil- dren. Pediatrics 1975;56:722-6.

[5] Hoekaday JM. Basilar artery migraine in childhood. Dev Med Child Neurol 1979;21:455-63.

[6] Aieardi J, Krageloh I. Alternating hemiplegia in infants: Report of five cases. Dev Med Child Neurol 1980;22:784-90.

[7] Casaer E Flunarizine in alternating hemiplegia in childhood. An international study in twelve children. Neuropediatrics 1987;18: 191-5.

[8] Holmes B, Brodgen RN, Heel RC, Speight TM, Avery GS. Flunarizine: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs 1984;27:6-44.

[9] Casaer P. Flunarizine in alternating hemiplegia in childhood. Lancet 1984;ii:579.

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