Electroencephalograph), and clinical Neurophysiology, 1985, 62:235-240 235 Elsevier Scientific Publishers Ireland, Ltd.

S O M A T O S E N S O R Y E V O K E D P O T E N T I A L S IN H U N T I N G T O N ' S CHOREA

EDWARD L. BOLLEN . .1 RUDOLF J. ARTS **, RAYMUND A. ROOS *, EDO A. VAN DER VELDE *** and ONNO J. BURUMA *

• Department of Neurology, Academic Hospital Leiden, 2333 A L Leiden, ** Department of Clinical Neurophysiology, Academic Hospital Leiden, 2333 AA Leiden, and *** Department of Medical Statistics, State University of Leiden, 2333 A L Leiden (The Netherlands)

(Accepted for publication: January 16, 1985)

Summary Somatosensory evoked potentials were measured in 21 patients with Huntington's chorea and 12 controls. Central brain conduction time was normal. Early cortical component amplitudes were reduced in the patient group, latencies were normal. These abnormalities probably can be attributed to cortical dysfunction in Huntington's chorea. No indication of brain-stem dysfunction was found.

Keywords: somatosensory evoked potentials (SSEPs) - - Huntington's chorea

In Hun t ing ton ' s chorea (HC) confl ic t ing results have been repor ted concern ing somatosensory evoked potent ia l s (SSEPs). Late cort ical compo- nent ampl i tudes have been repor ted to be in- creased (Paulson 1979) as well as decreased (Oepen et al. 1981). Ear ly cort ical componen t ampl i tudes have been found normal by some authors (Josias- sen et al. 1982) and decreased by others (Ehle et al. 1984; No th et al. 1984). Drug effects on SSEP have been ra ther neglected (Saletu 1974; Oepen et al. 1981; Josiassen et al. 1982; N o t h et al. 1984). Therefore, it seemed worthwhi le to re -examine SSEPs in HC.

tive family h is tory for HC. Five pat ients showed modera t e to severe cognit ive impai rment . There were nei ther signs nor symptoms indicat ive of o ther neurologica l disease. Four t een pa t ien ts were taking drugs. Med ica t ion had not been changed in the 3 months p r io r to the s tudy (Table I). The spouses, whenever available, were used as controls (12 controls , 6 males and 6 females, age range 26 -51 years, mean 48.8 years). The controls showed nei ther signs nor symptoms indicat ive of neuro- logical disease and were not on any kind of medi- cat ion.

Patients

After in fo rmed consent was ob ta ined accord ing to the Hels inki Dec la ra t ion of 1975, 21 pa t ien ts suffer ing f rom H C were s tudied (11 males, 10 females). Age ranged from 29 to 54 years (mean 47.5 years). The du ra t ion of the illness var ied f rom 1 to 9 years (mean 4.7 years). Al l pa t ien ts showed character is t ic choreic movements and had a posi-

1 Reprint requests to: Dr. E.L. Bollen, Dept. of Neurology, Academic Hospital Leiden, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands.

TABLE I

The fourteen patients using drugs.

Drug Daily dosage No. of patients * (mg)

Tetrabenazine 50-100 4 Tiapride 100-400 4 Haloperidol 2- 4 2 Tiopropazate 10 1 Diazepam 5 2 Chlordiazepoxide 10 l Amitriptyline 25 1 Imipramine 25 1

* Two patients used a combination of tetrabenazine and di- azepam.

0168-5597,/85/$03.30 © 1985 Elsevier Scientific Publishers Ireland, Ltd.

236 E.L. B O L L E N ET AL.

Methods

The subjects were studied lying supine on a couch in a warm, quiet, semi-darkened room. Square wave electrical pulses of 0.2 msec were delivered to the right median nerve at the wrist and to the right posterior tibial nerve at the ankle (Desmedt and NoEl 1973; Wilson et al. 1981). The intensity was at least 4 mA above motor threshold. The stimulus frequency was 4.8 Hz. The amplifier frequency response was 5-3000 Hz. The time base (512 points) of the averager was 5.5 msec (median nerve stimulation) and 11.0 msec (posterior tibial nerve stimulation) and the sampling rate was 500 kHz. Several runs of trials were performed. The electrodes were placed at Erb's point, at the pos-

T A B L E II

Early cortical c o m p o n e n t latencies in msec.

terior midline of the neck, at the C7 level and on the scalp overlying the contralateral parietal cortex for median nerve stimulation while a one-channel average was obtained from a vertex-to-frontal de- rivation for tibial nerve stimulation. All channels were averaged simultaneously. Samples with exces- sive electromyographic interference were automati- cally rejected. The following waves were recorded:

Median nerve stimulation: the N13/14 wave in the neck to midfrontal reference record, measured to the peak of the largest amplitude and the N20 and P25/3o wave in the parietal-midfrontal refer- ence record.

Posterior tibial nerve stimulation: the N35, P40, Ns0, P60 and N80 waves in the parietal-midfrontal

NI3- 20 P25/30 * difference *

p c P

N35 ** P40 ** Nso ** P60 ** Nso **

C P C P C P C P C P C

M e a n _+

3 S.D.

- 6 27.1 38.1

13.4 4.1 30.5 27 37

10.3 28.6 34.3

5 23.5 45.3

5.9 5 25.7 -

6.8 - 27.1 -

7 5.9 23.1 28.2 -

6.4 5.5 22.1 28.9 36.6

5 5.8 28.7 27.8 48.8

6.4 6 21.5 29.9 34.9

6.6 29 34.1

6.2 22.3 -

7 28.4 -

5.2 4.8 22.6 21.8 33.9

6.2 7.8 28.1 28.2 33.4

4.1 7.3 22.1 28 -

- 32.1 38.5

6.6 20.3 40.5

4.4 6 23.8 23 43.1

6.5 20.6 -

5.4 21.7 32.7

6.5 5.9 24.9 26.9 37.9 + + + + +

6.6 3 11.4 6.9 14.7

NS *** NS NS

36.3 - 41.1

36.7 - 46.4

40.3

51

45.1 - 49.2

33.7 - 38.1

36 - 42.5

38 40 45.5

41.4 51.5 46.2

43.4 39.5 49.8

41.8

33.2 40.7 37.8

37.4 39.6 42.9

36.5 - 42.5

42

48.6

35.4 47.2 41

36.5

37.7 43.2 43.6 + + +

11.1 15 11.7

NS

- 50.4 - 66.2 - 84.7

- 54.6 - 66.7 - 77.2

47.5 60.3 70.6

- 52.6 - 62.2 71.3

47.8 - 57.7 70.5

53.7 - 63 - 77.3

45.8 53.7 61.4 62.7 78.7 85.7

50.8 - 61.4 82,6 78.5

49.1 55.2 56.2 64.9 71.3 79.8

- 7 1 . 9

55.2 47.3 61.6 59.4 73,9 75.7

47.5 50.2 63.4 65.3 84.3 81.6

- 51.3 - 69.7 91.3

50.2 55.4 72.2

69.1 88.2 -

56.1 52.4 63.8 62.5 74.4 79

46.2 55 74

51.8 51.7 62.8 63.5 75.4 79.4 + + + + + +

22.2 22.8 30.1 9.9 14.4 17.7

NS NS NS

* Median nerve s t imulat ion.

** Posterior tibial nerve st imulation.

*** N o t statistically significant accord ing to the M a n n - W h i t n e y U test.

, no peak obta ined; P, pat ients; C, controls.

SSEP IN HUNTINGTON'S CHOREA 237

reference record (nomenclature according to Donchin et al. 1977).

Individual complex latencies and the N13/14-N2o latency differences were measured while ampli- tudes were expressed as Nzo-P25 , N35-P40 , N35-Nso, Nso-P6o and N6o-Nso peak-to-peak amplitude dif- ferences. Statistical evaluation was performed with the Mann-Whitney U test.

Results

N13/14 was obtained in all patients, N2o in 18 patients, P25/3o in 18, N35 in 14, P4o in 14, Nso in 9, P6o in 9 and Nso in 10 patients. In the controls all complexes were obtained except P4o in one. The N13/14-N2o latency differences were not prolonged

in our patient group, as compared with control values (Table II). Two of the patients had an Nt3/14-N2o latency difference exceeding 7 msec. This was probably due to flattening and distortion of the N20 complex shape since the ascending slope of the N20 wave in these patients had a duration of 5.4 and 6.7 msec respectively, measured from the start of the upward deflection to the peak, and since in both patients latency to the onset of the upward deflection (18 and 18.5 msec respectively) was within control limits (mean_+ 2 S.D. of the control group). The early cortical component latencies on posterior tibial nerve stimulation did not differ from those of the controls (Table II). The Nzo-P25 /3 o peak-to-peak amplitude difference in median nerve stimulation was significantly re- duced as compared with the controls (Table III

TABLE III

Early cortical component peak-to-peak amplitude differences in t~V.

P20-P25/30 * N35-P40 ** p40-Nso ** Nso-P60 ** p60-N8o **

P C P C P C P C P C

Mean ±

3S.D.

0 0.8 0 0.3 0 1.1 1 2.3 0 0.4 0 0.5

1.7 0.6 0.6 0.7 0.9 0

0 5.3 0 1.5 0 0.9 0 2.3 0 1.6 0 2

1.8 3.3 0 3.8 0 4

2.3 7.4 0.2 2.5 0.8 5

1.7 4.4 0.2 0.5 0 0.1

3.5 3.3 2.3 0.7 2.5 0.4

0.1 2.4 2.9

0.8 0 0

1.4 0 0

0.6 4 0.3 1.4 0.5 2.5

2 2 1.5 0.8 2.9 1.2

1.7 11 0 3.6 0 3.8

2.3 0.2 0.6

O.5 0.4 0.9 0.6 1.5 1.2 1.2 0.7 1.3

1.8 0 0 2.5 1.1 1.1

1.28 3.96 0.58 1.57 0.64 1.9 ± ± ± ± ± ±

2.7 8.4 2.1 3.3 2.9 4.8

P***:0 .006 P * * * : 0 . ~ 4 P***:0.004

0 2.2 0 3.5 0 0.5 0 0.9 0.5 0.5

0 0

0 2.1 0 2.3

0 3.9 0 4.1

0 2.5 0 4.7

1.9 2.6 3.5 6.5

0 1.6 1.6 4

2.4 1.3 6.4 3.2

0 0

0 0

0 0

0.3 1.2 0.8 4.2 2.9 1.6 4.5 2.9

0 6 0 4.4 0.4 0.9

1.2 0

0.4 1 1.4 1.4

0 0 0.8 2.9

0.51 2.2 1.1 3.5 ± ± ± ±

2.6 4.5 5.4 4.6

P * * * : 0 . 0 ~ 2 P***:0 .0005

* Median nerve stimulation. ** Posterior tibial nerve stimulation.

*** According to the Mann-Whitney U test.

238 E.L BOLLEN ET AL.

lqe=

!q5

A ~

Iq8

U V L T

STIM.N.MED

Z S / 3 0

ST IM .N .T IB NB~

NS~

_ _ _ _ A I i I J [ I I I i _ M s e : c

Fig. 1. SSEP in a control. Upper 3 traces: median nerve stimulation. Time base: 5.5 msec per division, 2.5 #V per division. Lower trace: posterior tibial nerve stimulation. Time base: 11.0 msec per division, 1.25/*V per division.

S T I P I . N . M E D U V L T

8 5

B 2

Bk,

B 1

! 8T |M .N .T IB N8(3

l a l

I I I I I [ I I 1 . MSEC

Fig. 2. SSEP in a patmnt with Huntington's chorea. 1.25 #V per division for median nerve stimulation and 0.62 /*V per division for posterior tibial nerve stimulation. Further data as in Fig. 1.

and Fig. 1). The same was observed for the N3s-P40,

P40-Nso, Nso-P60, P60-Nso peak-to-peak ampli tude differences in posterior tibial nerve s t imulat ion

(Table III and Fig. 2).

Discussion

Central brain conduc t ion time (CBCT) is mea-

sured by subtract ing N13/14 latency (origin par- tially in the spinal cord, C6-C 7 level and partially in the medial lemniscus in the caudal brain-stem, Desmedt and Cheron 1980a, 1982). CBCT is inde-

penden t from peripheral nerve conduct ion velocity (Hume and Cant 1978). Confl ict ing results with

respect to CBCT, early cortical componen t laten- cies and ampli tudes in HC have been reported and are reviewed in Table IV. We found no statistically

significant differences in CBCT and early cortical componen t latencies between our patients and the controls. Absence of an SSEP complex may be

caused by extreme ampl i tude decrease. Because we did not find differences in early cortical compo- nent iatencies, if measurable, between pat ients and

controls, absent complexes were considered as hav- ing zero ampli tude. The normal findings of Josias- sen et al. (1982), contrast ing with early cortical

componen t ampli tude decrease found by Ehle et

TABLE IV

Review of reports on central brain conduction time (CBCT), early cortical component latency (ECCL) and amplitude (ECCA) on median rierve stimulation (mns) and on posterior tibial nerve stimulation (ptns).

Josiassen Noth Ehle Present et al. (1982) et al. (1984) et al. (1984) study

prolonged normal normal normal prolonged normal normal

CBCT ECCL

mns ECCA

mns

ECCL ptns

ECCA pins

normal decreased decreased decreased N20 N20 N2o P3o P25/3o

normal normal

decreased - decreased before 50 msec before and

after 50 pronounced msec component after 50 msec

SSEP IN HUNTINGTON'S CHOREA 239

al. (1984) and ourselves, may be explained by the fact that our patients, like the patients of Ehle et al. (1984), were on average in a more advanced stage of the disease. Noth et al. (1984) reported early cortical component amplitudes to decrease considerably in the early stage of the disease and to decrease only moderately with progressing dis- ease. However, they did not mention the duration of the disease in their patients.

Noth et al. (1984) found decreased N33-P40 waves to be followed by a relatively pronounced second component on tibial nerve stimulation and as- sumed these findings to be typical for HC. They did not specify this second component, but from one of their figures it can be deduced that it is composed of the Ns0, P60 and Ns0 waves. We found P40-Nso, Nso-P60 and P60-Nso peak-to-peak amplitude differences to be smaller in our patients than in controls. Patients with absent Nso, P60 and Nso waves were even more frequent than patients with absent N35 and P40 waves. In contrast to Noth et al. (1984) our results indicate amplitude de- crease of all early SSEP cortical components in HC, most pronounced after 50 msec.

Decreased early cortical component amplitudes with normal latencies are not characteristic for HC, but are thought to reflect cortical dysfunction (Stohr et al. 1982). Similar abnormalities have been observed in visual evoked potentials in HC (Josiassen et al. 1984). Whether cortical atrophy is a sufficient explanation is questionable, because increased SSEP amplitudes have been described in human cortical atrophy in aging (Desmedt and Cheron 1980b).

Dopamine receptor blockade appears to result in decreased cortical SSEP amplitudes, although in the presence of increased latencies (Saletu et al. 1972). Apart from the effect of dopamine receptor blockers little attention has been paid to the in- fluence of drugs (Josiassen et al. 1982; Ehle et al. 1984; Noth et al. 1984). Diazepam has been re- ported to decrease cortical component amplitudes but this effect is always accompanied by an in- crease of cortical component latency (Saletu 1974). Chlordiazepoxide has been found not to influence early cortical component amplitudes (Saletu et al. 1972). Tricyclic antidepressants appear to increase early cortical component amplitudes (Saletu et al.

1973). Therefore our results cannot be explained by drug effects.

In conclusion, we found decreased early SSEP amplitudes with normal latencies on median nerve as well as on posterior tibial nerve stimulation in a group of 21 patients with HC. In contrast to a previous report (Noth et al. 1984) we found ampli- tude decrease to be more pronounced in the com- ponents after 50 msec on posterior tibial nerve stimulation. These abnormalities are probably to be attributed to cortical dysfunction in HC, No indication of brain-stem dysfunction was found.

Resum~

Potentiels bvoqubs somatosensoriels clans la chorbe de Huntington

Les potentieis 6voqu6s somatosensoriels ont 6t6 enregistr6s chez 21 patients souffrants de la chor6e de Huntington et chez 12 sujets normaux. La dur6e de la conduction dans le tronc c6r6bral 6tait normale chez les patients, les amplitudes des com- posantes corticales ~ courte latence 6taient di- minu6es, leurs latences 6taient normales. Ces r6sultats sont probablement dus a une dysfunction au niveau cortical dans la chor6e de Huntington. La fonction du tronc c6r6bral apparaissait nor- male.

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