Evoked potentials in choreoacanthocytosis

349

Electroencephalography and clinical Neurophysiology, 1986, 6 3 : 3 4 9 - 3 5 2 Elsevier Scientific Publishers Ireland, Ltd.

Short communication EVOKED POTENTIALS IN CHOREOACANTHOCYTOSlS PETER W. K A P L A N , C H A R L E S W. ERWIN, M I C H A E L H. B O W M A N and E. W A Y N E MASSEY Duke University Medical Center, Box 2976, Durham, NC 27710 (U.S.A.)

(Accepted for publication: December 2, 1985)

Summary Visual, brain-stem auditory and somatosensory evoked potentials were obtained in two patients with choreoacanthocytosis. Only minor SSEP amplitude reduction was found in one patient. Therefore evoked potentials were not helpful in identifying patients with symptoms of this disorder of up to 8 years duration.

Keywords: choreoacanthocytosis - Huntington's disease - evoked potentials

Choreoacanthocytosis (CA) is a rare, autosomal dominant disorder characterized by chorea, erythrocyte acanthocytosis, areflexia and raised serum creatine phosphokinase. As in Huntington's disease (HD), there is progressive chorea, and neuronal loss with gliosis in the putamen and caudate nuclei. Unlike HD, there is no dementia or it occurs late. Abnormalities in visual evoked potentials (VEPs) and short latency somatosensory evoked potentials (SSEPs) (Ellenberger et al. 1978; Oepen et al. 1981) have been reported. We studied two patients with CA to determine any possible abnormality in evoked potentials that accompanies the established clinical and pathological changes found in this disease.

Case 1 A 37-year-old white male shipping clerk had a 5 year history of stuttering speech and involuntary biting of the inside of his mouth. Increasing difficulty swallowing and drooling from the mouth appeared over the ensuing months, as well as clumsiness of his hands, unsteadiness of gait and irregular, j u m p i n g movements of all limbs. Problems with recent memory also were noted. The mental status was normal, speech dysarthric and ophthalmological exam normal. The cranial nerves were intact, but involuntary chewing movements of the mouth were seen. Power, tone and sensation were normal excepting a diminished vibratory perception at the ankles. Abrupt, choreiform movements of the 4 limbs, with attempts to disguise the movements, were noted. Gait was awkward with a tendency to lurch in different directions. Tendon reflexes were diffusely diminished and absent at the ankles. Plantar reflexes were flexor. Abnormally increased acanthocytes on blood smear and raised creatine phosphokinase (900 IU) were found. Serum copper, ceruloplasmin, urine copper and heavy metals were normal. Electromyography and nerve conduction studies revealed low amplitude sensory responses in the upper and lower limbs with distal limb muscle reinnervation changes indicative

of a mild distal sensorimotor neuropathy. CT and magnetic resonance imaging (MRI) revealed bilateral caudate atrophy. E E G was normal.

Case 2 A 43-year-old white male factory worker presented with an 8 year history of slowly progressive choreiform movements, initially affecting the legs and subsequently the arms. Orofacial dyskinesia developed with progressively dysarthric speech, agitation and increasing forgetfulness. Examination revealed choreiform movements in the 4 limbs and an ataxic gait. Hyporeflexia with normal tone, strength and sensation was found. Full scale IQ was 82 (performance score of 79 and verbal of 85), a result similar to that obtained in high school. The C P K was 2802 I U / I (97% M M banding). The aldolase was 15.3 IU/1 and a fresh blood smear showed 30% acanthocytes. Liver enzymes, vitamin E levels, lipid profile, ceruloplasmin, serum and urinary copper and heavy metal screen were normal. A head CT scan demonstrated caudate atrophy.

Methods Averaged responses were replicated and wave forms superimposed to document reproducibility. Limits of normal were determined in the 'Guidelines for clinical evoked potential studies' of the American Electroencephalographic Society (1984). All reference to electrode placement is based on the 1 0 / 2 0 international system. The pattern reversal evoked potentials (PREPs) were obtained using an alternating black-and-white checkerboard pattern, produced electronically on a television monitor. Check size subtended 28 min of visual angle. Contrast was measured at 55% (Erwin 1980). Low and high frequency filters were set at 1 and 250 c/sec, respectively. Patient alertness and visual

0013-4649/86/$03.50 © 1986 Elsevier Scientific Publishers Ireland, Ltd.

350

P.W. K A P L A N ET AL.

TABLEI VEP

BAEP

Latency

Amplitude

Left Wave

Right

P100

Latency

Left

Right

P100

Left

Right

I,Vc

l-Vc

4,4 4.0

4.2 3.9

(a) VEP latencies (msec) and amplitudes (#V); BAEP latencies (msec) Patient 1 Patient 2

94 95

92 96.5

4.6 6.4

5.4 6.0

(b) SSEP latencies (msec) and amplitudes (#V) Median

Tibial

Latency Left Wave Patient 1 Patient 2

Amplitude Right

--

EP-N20 8.9 9.3

Left

Latency Right

Left m

N20/P25 8.7 9.1

3.9 2.5

Amplitude Right

PF-P37 2.1 2.8

30.7 29.8

Left

Right

P37/N45 29.6 30.7

0.35 1.1

0.46 1.2

Laboratory norms at 99% tolerance limit: VEP P100 latency = 108 msec; BAEP I - V c IPL = 4.6 msec; SSEP median E P - N 2 0 = 11.5 msec; SSEP tibial PF-P37 = 35.0 msec.

fixation on the target were monitored. Between 200 and 400 responses were averaged over 250 msec using a 4-channel montage that included an Oz-Fz derivation. The triphasic negative-positive-negative response in the Oz-Fz derivation was identified and evaluated with respect to the absolute latency of the major positive component (P100). Laboratory normative data for this age group equals 97.5 msec, upper tolerance limit equals 108 msec (99% proportion, 95% confidence). Brain-stem auditory evoked potentials (BAEPs) were obtained by delivering a 100/~ sec square wave impulse at 11.1/sec to transducers producing a 70 dB HL rarefaction click. White noise was provided at 30 dB HL to the non-stimulated ear. Responses were recorded using a 2-channel montage (Cz-A1, Cz-A2) and each trial contained 2000-4000 responses averaged over 10 msec. High pass (HP) and low pass (LP) filters were set at 150 and 3000 Hz respectively. The I - V interpeak latency (IPL) was used as the primary criterion of abnormality with the upper tolerance limits of normal (4.6 #see) being adjusted for age and gender. Short latency somatosensory evoked potentials (SSEPs) were recorded after electrical stimulation of the median nerve at the wrist and the tibial nerve at the ankle. A 100 #sec, 6 - 2 0 mA pulse (adjusted to obtain a vigorous muscle twitch) was delivered at a rate of 5.4/sec. Recording electrodes were placed at Erb's point (EP), fifth cervical vertebra (C5S), Fpz, C3', C4' and at Cz' (American EEG Society 1984). The contralateral knee or ankle was used as a non-cephalic reference (NCR). For median nerve studies, the 4-channel montage was: EP1-EP2, C5S-Fpz, CY or C 4 ' - N C R and CY or C4'-Fpz (scalp lead contralateral to limb stimulated). Analysis time was 30 msec

and 1500-3000 responses were averaged with HP and LP filters at 30 Hz and 3000 Hz, respectively. Interpretation was primarily based on EP-N20 interpeak latency (99% T L = l l . 5 msec).

Tibial nerve response analysis time was 80 msec. The 4channel montage was: bipolar popliteal fossa (PF), third lumbar to twelfth thoracic vertebra (L3S-T12S), CS5-Fpz and Cz'-Fpz. Interpretation of central conduction was based on the IPL between the major negativity of the spinal response and P37 (99% TL = 23 msec) or the IPL PF-P37 (99% TL = 35 msec) in those cases in which the spinal response is of low quality.

Results The VEP, BAEP and SSEP absolute and interpeak latencies were within normal limits (Table la and b).

Discussion Choreoacanthocytosis (CA), like Huntington's disease (kiD), causes progressive chorea and atrophy of the caudate nuclei (Bird et al. 1978). Additionally, variable clinical features have been reported in CA, including major motor seizures, diminished tendon reflexes and prominent tongue biting, Laboratory investigations have revealed erythrocyte acanthocytosis, low cholesterol, normal fl-lipoprotein and raised CPK (Kito et al. 1980). Unlike HD, severe and progressive dementia is not part of the syndrome.

E V O K E D P O T E N T I A L S IN C H O R E O A C A N T H O C Y T O S I S Evoked potential studies have been reported to be abnormal in patients with HD and in at-risk members of the immediate family (Oepen 1982; N o t h et al. 1984). The mean amplitude of the early and late components of the VEPs was found to be diminished in H D patients when obtained by flash stimulus (Ellenberger et al. 1978) and pattern reversal stimulus (Josiassen et al. 1984). Other investigators have failed to corroborate these abnormalities (Ehle et al. 1984). Opposing results also have been obtained with BAEPs in patients with HD. Thus, Josiassen et al. (1984) found normal peak latencies with diminished amplitudes, but Ehle et al. (1984) showed no abnormalities. SSEP studies in H D patients have shown a slight prolongation of the late peaks with attenuation or absence of the late components (Oepen et al. 1981). In addition, amplitude diminution in the early components (N20/P25 for the median nerve and N 3 3 / P 4 0 for the tibial nerve) was obtained by Noth et al. (1984) and diminution of the N20-P25/30 median nerve and N35-P40 tibial nerve components by Bollen et al. (1985). Although no latency abnormalities were found in the present study of 2 patients with choreoacantbocytosis, there was reduced amplitude of the N 3 7 / P 4 5 component in patient 1. Similar amplitude changes have been found in other neurological disorders involving the brain-stem and cortical structures (Chiappa et al. 1980; Stohr et al. 1982). Takahashi and Okada (1972) believe that caudate atrophy may account for the diminished amplitude, although a more non-specific deficit in thalamic and thalamo-striato-cortical pathways has been suggested by McCaughty (1961). Amplitude as a criterion of abnormality m a y be used in group data (comparing individuals with a common diagnosis with matched normal subjects) in a statistically valid fashion. When differences are discovered, they m a y reveal information regarding the mode of action of a specific disease process. Both attenuations and potentiations have been reported in different diseases. The use of amplitude as a criterion of abnormality in a specific individual is usually inappropriate. Numerous nonphysiological factors can and do affect amplitude. In addition, amplitude is generally not distributed in a normal fashion; the mean minus 2 - 3 S.D.s usually results in a value less than zero. This can be resolved by transformation of the data (American EEG Society 1984), but even this is not usually successful in a clinical setting. Short of absence of an obligatory wave, low amplitude as a criterion of abnormality will produce excessive false positive results. Clearly, one of our patients had entirely normal amplitudes (patient 2) while the other (patient 1), with lower than average amplitudes, additionally had a peripheral neuropathy that might have contributed to this finding. Noth et al. (1984) reported normal evoked potentials in other choreiform disorders such as benign familial chorea, Wilson's disease and kernicterus. Acanthocytosis and ataxia also occur in abetalipoproteinemia, but there is prolongation in central conduction time of the SSEP, thought to be secondary to the neuropathy and dorsal column demyelination associated with vitamin E deficiency (Johnson 1985). As was noted with HD, it is possible that in CA, the disease progression and increasing neuronal loss may eventually lead to

351 abnormalities in the evoked potentials. Without consistent, well-defined abnormalities in the evoked potentials, identification of CA family members at risk or longitudinal follow-up of affected individuals does not appear to be practicable.

Resum~ Potentiels b~,oquks dans des cas de chorkoacanthocytose

Des potentiels 6voqurs visuels, somatosensoriels et auditifs du tronc crrrbral ont 6t6 obtenus chez deux patients atteints de chorroacanthocytose. Seule une faible reduction d'amplitude du PESS a pu dtre trouvre, et chez un seul des deux patients. Les potentiels 6voqurs ne sont donc d'aucune utilit6 pour identifier des patients dont les s y m p t r m e s de la maladie peuvent dater de 8 ans.

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