Antiepileptic drug effects on somatosensory evoked potentials

/ Eyilrpsy

1989;2:165-168

@ 1989 Demos Publications

Antiepileptic

Drug Effects on Somatosensory Evoked Potentials

lm3Miles E. Drake, Jr., ‘<‘Ann Pakalnis, ‘f3Sharon A. Hietter, and 2Lena S. Denio

Some evoked potential changes have been documented in chronic phenytoin (PHT), valproate (VPA), or benzodiazepine therapy, whereas other studies have suggested little change with carbamazepine (CBZ) or phenobarbital (PB). We recorded median and posterior tibia1 nerve somatosensory evoked potentials (SET’s) in complex partial seizure patients taking PHT, CBZ, or VPA in monotherapy with stable therapeutic serum levels and no toxic symptoms. Ten patients each were studied with PHT, CBZ, and VPA and were compared with agematched controls. Median nerve responses were recorded at Erb’s point, cervical spine, and contralateral cerebral sites; tibia1 nerve evoked potentials were recorded from popliteal fossa, lumbar, cervical spine, and midline scalp electrodes. Epileptic patients and controls did not differ in SEE’ latency, amplitude, or central condition time. PHT prolonged Erb’s point and popliteal fossa latencies, but not central conduction time. CBZ had no effect on latencies or amplitudes. Evoked potential amplitudes were reduced by VPA, and cortical response latencies were minimally prolonged. Chronic antiepileptic therapy without toxicity had little effect on SEE’s F’HT may have a slight effect on peripheral nerve conduction, and VPA may have an effect on amplitude of cerebral responses. Key Words: Somatosensory evoked potentials-EpilepsyAntiepileptic drugs.

Evoked potentials are widely used in neurologic diagnosis but have been studied relatively infrequently in epilepsy (l-5). Somatosensory evoked potentials (SEPs) were first recorded in myoclonic epilepsy (6) but have only occasionally been studied in other types of seizures and in relation to antiepileptic drug therapy (7-10). Evoked potentials are sometimes affected by medications and could therefore be altered in latency or amplitude by chronic effects of From the ‘Department of Neurology, 2Comprehensive Epilepsy Program, and 3Clinical Neurophysiology Laboratory, The Ohio State University Hospitals and College of Medicine, Columbus, OH, U.S.A. Presented at the 42nd Annual Meeting American Epilepsy Society, San Francisco, October 18, 1988. Address correspondence and reprint requests to Dr. M.E. Drake, Jr., at 466 Means Hall, 1654 Upham Drive, Columbus, OH 43210, U.S.A.

antiepileptic drugs. Evoked potentials may also be a noninvasive means of monitoring the chronic effects of antiepileptic drugs on central and peripheral nervous system function; since somatosensory evoked potentials assessthe most neural tissue of the standard evoked potential modalities, they might be particularly sensitive as a measure of cumulative medication effect. We have compared the effects of several different antiepileptic medications on short latency components of SEPs in patients taking monotherapy for partial or generalized seizure disorders.

Subjects and Methods Thirty epileptic patients and 10 normal control subjects were compared. Ten patients were taking phenytoin (PHT) for complex partial (six patients), partial and secondarily generalized (three patients), 1 EPILEPSY, VOL. 2, NO. 3, 1989

165

M. E. DRAKE, ]R., ET AL. or generalized (one patient) seizures; six were men and four were women, and ages ranged from 19 to 46 years. Ten patients were taking carbamazepine (CBZ) for complex partial (nine patients) or generalized (1 patient) seizures, ranging in age from 23 to 60 years and being equally divided between the sexes. Ten patients, seven male and three female, ranged from 18 to 49 years of age and were taking valproate (WA) for complex partial seizures (five patients), partial and secondarily generalized seizures (two patients), or generalized seizures (three patients). Five control subjects were men and five women, and they were 25-56 years old. Seizure patients and controls had normal neurologic examinations and computed tomography scans or magnetic resonance studies of the brain. All seizure patients had abnormal EEGs with focal or bilaterally synchronous epileptiform activity, but EEG background was normal except for the interictal epileptiform paroxysms or recorded seizures. All patients had been on monotherapy for at least 6 months, with stable antiepileptic drug levels within the respective therapeutic ranges and with no toxic signs or symptoms. No patients had other neurologic disorders or medical conditions affecting the central or peripheral nervous system, and none was taking other prescription medications. The control subjects were free of medical and neurologic disorders and were taking no medications. SEPs were recorded to right and left median and posterior tibia1 nerve stimulation at the wrist and ankle, respectively, with 300-p current pulses suffiTable 1.

cient in intensity to produce a motor twitch. These were delivered at 5.1/s, and no muscle relaxants or sedatives were utilized. Median nerve responses were recorded from Erb’s point with reference to the contralateral supraclavicular region, C2 to Fz, C3’, or C4’ scalp electrodes (2 cm behind the C3 and C4 placements of the International lo-20 Electrode System) with reference to the contralateral shoulder, and C3’ or C4’ with reference to Fz. The following electrode derivation was utilized for tibia1 nerve recordings: ipsilateral to contralateral popliteal fossa, L.3-T5, C2Fz, and Cz’ (2 cm behind Cz) to Fz. Analysis times were 30 ms from median nerve responses and 100 ms for tibia1 nerve responses. Filter bandpass was 301,500 Hz, and 500 averages were recorded and replicated from stimulation of each nerve. The following components were measured after median nerve stimulation: NlO at Erb’s point, Nll/N13 at C2-Fz, N19/P23 at C3’ or C4’-Fz, and central conduction time between N13 and P23. From tibia1 nerve stimulation, NlO in the popliteal fossa, the caudal spinal response at L3-T5, N50/P60 at Cz’-Fz, and central conduction time from the caudal spinal response to P60 were measured.

Results Evoked potential latencies and central conduction times in controls and patients taking PHT, CBZ, and VPA are compared in Table 1.

Median and posterior tibia1 nerve sornatosemory evoked potential lutencies in normal controls and epileptic patients taking PHT, CBZ, and WA Latency (ms & SD) Controls

PHT

CBZ

VPA

Median nerve SEPs NlO N13 N19 P23 CCT (NlO-P23)"

10.01 12.98 19.76 22.83 12.78

f f + + +

0.88 0.96 0.86 1.01 0.68

11.02 kO.56" 13.14 + 0.66 20.09 kO.78 23.44 3~0.99 12.26 + 0.24

10.16 & 0.98 13.08 + 0.73 20.20 f 0.16 22.98 kO.86 12.84 iz 0.85

0.56 + 0.66 13.15 kO.86 20.44 + 0.88 23.88 + 0.64" 13.22 + 0.88

Tibia1 nerve SEPs PF L3 c7 N50 P60 N75 CCT (L3-l'60)h

9.62 f 20.60 f 29.00 f 41.44 + 52.80 f 64.48 f 31.94 +

1.04 1.08 1.87 2.66 5.92 4.61 3.21

11.01 kO.92" 21.94 + 2.66 30.84 + 2.08 42.26 + 2.94 52.68 k4.21 66.01 k4.22 33.85 f 5.26

10.00 -I 0.78 20.84 + 1.03 29.66 -t 5.31 42.61 f 2.82 53.80 f 1.96 66.00 zk 4.23 32.96 f 4.76

10.42 + 0.98 20.96 f 1.22 29.56 f 4.24 43.00 + 5.93 55.66 I!Z2.06" 67.04 + 2.87" 34.52 k3.68

“p < 0.05 compared to controls. bCCT, central conduction time. 166 J EPILEPSY,VOL. 2, NO. 3, 1989

ANTlEPILEPTlCS

No differences were demonstrable among the antiepileptic drug groups, and analysis of variance was therefore not applied. Comparison of seizure patients and controls using Student’s one-tailed t test showed a significantly longer N10 latency in patients on PHT monotherapy (p < 0.05). Median nerve P23 and P60 and N75 from posterior tibia1 nerve stimulation were significantly prolonged in patients on VPA as compared to controls (p < 0.05). Evoked potential amplitudes and central conduction times from median and posterior tibia1 nerve stimulation did not differ significantly between the patients on antiepileptic drugs and the controls.

Discussion SEE’swere initially recorded in patients with myoclonic epilepsy because of pathological enhancement of cortical SEE’s in this degenerative disorder (1). Broughton et al. (2,3) demonstrated enhanced SEE’s in photosensitive epilepsy, which was reduced by treatment with clonazepam or diazepam. Green et al. (4,5) found no effect on SEE’components of seizure type, epilepsy duration, seizure frequency, or EEG abnormality, although a relationship was found between PHT levels and response latency. Prolongation of cortical SET’swas found in Baltic myoclonic epilepsy by Mervaala et al. (6), and these investigators (7) also found prolongation of the median nerve P22 component in primary generalized epilepsy. The effects on SEPs of a variety of antiepileptic drugs have been studied in patients with head injury, in whom SEPs were used as a prognostic tool, and in small numbers of epileptic patients. Hume et al. (8) found no relationship in comatose patients between PB levels and upper limb SEP central conduction time. Intravenous diazepam infusion in four children produced no apparent change in the median nerve N19 potential, but there was a latency shift in the P25 component (9). Hume and Cant (10) found that PB level and body temperature together were responsible For only 4% of the variance of SEE’central conduction time after head injury. Sutton et al. (11) found no effects of pentobarbital narcosis on SEE’sin cats. AlLhough epilepsy did not affect SEP latencies in the study of Green et al. (4), age, sex, and serum PHT level were related to SEP central conduction time, and disinct effects were found by analysis of variance and :oxic and therapeutic serum levels. The enhanced :ortical SEPs of myoclonic epilepsy were studied by jhibasaki et al. (12), who found them to be reduced 2y 5-hydroxytryptophan treatment, which is in ac:ord with previous evidence of their benzodiazepine sensitivity (3). Borah and Matheshwari (13) found no

AND SOMATOSENSORY

EVOKED POTENTIALS

SEE’changes during 3 months of monotherapy with CBZ, PHT, or PB in epileptic patients. Carenini and colleagues (14) followed patients on CBZ monotherapy for 1 year and noted no effect on SEPs. These findings are consistent with the general evidence that medications have little effect on short-latency SEP components and that epilepsy itself changes these potentials minimally, except in the setting of intoxication, encephalopathy, or degenerative disorder. PHT relatively prolonged peripheral somatosensory evoked responses in our population of predominantly partial and secondarily generalized seizure patients. This is consistent with its reported effects on peripheral nerve conduction (15). Although CBZ has been reported to slow peripheral nerve conduction (16,17), our patients, like those of Carenini et al. (14) showed no effects on peripheral or central SEP components. Cortical evoked potentials and central conduction times were prolonged in patients on VPA, which is in accordance with clinical (18) and neurophysiologic (19) evidence that the drug may have a direct central effect in some patients. Partial epilepsy in our patients had little effect on SEE’s,although some changes have been reported in myoclonic seizures (four patients) and generalized seizures (five patients). The latter changes may be due to associated encephalopathy or, in some patients, to polypharmacy. Polypharmacy may synergistically prolong the latencies of visual and auditory evoked potentials in comparison to monotherapy (20), but the comparative effects of monotherapy and polypharmacy on SEPs remain to be investigated. Longerlatency SEE’ components or spectral or topographic analysis of evoked potentials may be more sensitive to the effects of chronic antiepileptic drug therapy on brain function. Acknowledgment: This work was supported by the Denman Fund for Epilepsy Research, The Ohio State University.

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M. E. DRAKE, ]R., ET AL. 5. Green JB, Walcoff MR, Lucke JF. Comparison of phenytoin and phenobarbital effects on far-field auditory and somatosensory evoked potentia! interpeak latencies. Epilepsia 1982;23:417-21. 6. Mervaala E, Partanen JV, KerXnen T, et al. Prolonged cortical somatosensory evoked potential latencies in progressive myoclonus epilepsy. J Neural Sci 1984;64: 131-5. 7. Mervaala E, Ke4nen T, Penttila M, et al. Pattern-reversal VEP and cortical SEE’ latency prolongation in epilepsy. Epilepsiu 1985;26:441-5. 8. Hume AL, Cant BR, Shaw NA. Central somatosensory conduction time in comatose patients. Am Neural 1979;5:379-84. 9. Prevec TS. Effect of Valium on the somatosensory evoked potentials. Prog Clin Neurophysiol1980;7:3118. 10. Hume AL, Cant BR Central somatosensory conduction after head injury. Am Newrol 1981;10:411-9. 11. Sutton TN, Frewen JT, Marsh R, et al. The effects of deep barbiturate coma on multimodality evoked potentials. J Neurosurg 1982;57:178-85. 12. Shibasaki H, Yamashita Y, Neshige R, et al. Pathogenesis of grant somatosensory evoked potentials in progressive myoclonic epilepsy. Braitl 1985;108:22540.

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