Cortical sensory evoked potentials and communicative forebrain functions
Lea Leinonen a, MScD, Mikko Sams b, PhD, Hannu Heiskala c, MD, Anu Klippi d, MA~ Anna-Maria Korhonen d, BA, Minna Hakap~i~i d, BA
Cortical evoked potentials were measured to visual, auditory and somatosensory stimuli in 20 subjects with serious neurodevelopmental impairments due to various etiologies. The results were compared with behavioral observations to find out whether the a b s e n c e / p r e s e n c e of the responses corresponded to the level of social functioning. No cortical evoked potentials were elicited in two subjects, responses to the stimulation of one modality were missing in three subjects (retinal b-waves and brainstem auditory and somatosensory evoked potentials were, however, preserved in them). No communicative behavior was observed in subjects with absent responses. Ten subjects had marked deviations in the evoked potentials, the behavioral observations in them, ranging from no communicat ion to sentenced speech. Five subjects had normal response patterns and they showed a great variety of communicative skills, including speech. The results support the view that bilateral loss of cortical somatosensory, visual, and auditory evoked potentials is a sign of loss of neural substrates of communication.
The absence of communication in subjects with se- vere neurodevelopmental impairments suggests ab- sence of forebrain functions required in social interac- tion. There are no generally accepted neurophysiologi- cal indices of such forebrain failure, however. They would aid the recognition of subjects who do not benefit from rehabilitation.
Bilateral loss of cortical somatosensory evoked po- tentials (SEPs) is associated with poor outcome (death or vegetative state) in comatose subjects with previous
a Department of Physiology, University of Helsinki, Helsinki, Fin- land; b Low Temperature Laboratory, Helsinki University of Tech- nology, Espoo, Finland; c Rinnekoti Institute for Mentally Retarded, Espoo, Finland, d Department of Phonetics, University of Helsinki, Helsinki, Finland
Received 17 May 1993; accepted 3 September 1993
Correspondence address: Dr. L. Leinonen, Department of Physiology, PO Box 9, SF-00014 University of Helsinki, Helsinki, Finland. Fax: (358) (0) 191 8681.
head trauma [1-4]. Absent visual evoked potentials (VEPs) have similar significance in perinatal asphyxia [4-10], in comatose children [9,11], and in adults with closed head trauma [12]. The prognostic significance of cortical auditory evoked potentials (AEPs) has been studied only occasionally; the observations in subjects with head trauma suggest that their absence is also associated with poor prognosis [13].
The observations on the prognostic value of SEP and VEP in acute cerebral lesions led us to suggest that their absence would correspond to severe fore- brain failure regardless of the etiology of the condition. This hypothesis was studied in 20 subjects with severe neurodevelopmental impairments of various etiologies. Epilepsy is a common consequence of severe brain damage; in Rinnekoti Institute for Mentally Retarded, where the study was performed, more than 80% of such subjects have epilepsy. The anti-epileptic medica- tion may affect the evoked potential amplitudes and latencies [14-16]. We studied only subjects receiving medication.
Cortical responses were measured to visual, audi- tory, and somatosensory stimuli. The functioning of the
L. Lemonen et al. / Brain & Development 1994; 16:32-9 33
eye, ear, and peripheral somatosensory system was evaluated by electrophysiological means, too. In order to determine the behavioral significance of the results, they were compared with the neurological deficits and communicative skills of the subjects.
2. METHODS
2.1. Subjects Twenty subjects with severe neurodevelopmental
disorders due to various etiologies (Table 1), and with various ictal manifestations and intermittent general- ized slow spike-wave complexes in EEG were studied in Rinnekoti Institute for Mentally Retarded. The study was accepted by the ethical committee of the institute, and the relatives of the patients gave their informed consent.
2.2. Evoked potential measurements Evoked potentials were measured on four channels
(Neuropack four mini, Nihon-Kohden). Needle elec- trodes were used on the scalp, and adhesive electrodes on the face, neck, and chest. Automatic artefact rejec- tion was used in all measurements. Each measurement was repeated two or three times, and the records averaged. The subjects with missing responses to any stimulation were studied repeatedly on two different days. The response amplitudes were determined with reference to a 20 or 50 ms pre-stimulus baseline.
Waking and sleep EEG were recorded from all subjects during the course of the study. During the
evoked potential measurements, E E G from the deriva- tions used was also monitored. No measurements were performed during seizures.
20-Hz rarefaction clicks (monaural stimulation at 30- 100 dBnHL; from frontal midline to the earlobes; passband 0.1-5 kHz; repeated averages of 1,500-2,000 responses) were measured to ascertain whether the stimulus intensity during the AEP measurements was clearly above the ear threshold for click-stimuli. The mesencephalic response (wave V) was obtained in all subjects in response to stimulation of both ears with normal or delayed latency (5.3-7.0 ms).
AEPs were measured with 1-kHz tones (50 ms dura- tion, 10 ms rise and fall time) using 0.5 and 2-s inter- stimulus intervals. The intensity of the tone was ad- justed between 70 and 100 dBnHL, depending on the BAEP threshold for the click stimulus. The electrodes at the midline (Fpz, Fz, Cz, and Pz) were refered to an electrode on the left earlobe (passband 1 Hz-50 Hz; analysis time 500 ms, 2-3 repeated averages of 100-200 responses). Blink artefacts were monitored and re- jected with the electrode at Fpz. In some subjects interference from reflex blinking could not be avoided. Many subjects needed intermittent somatosensory or visual stimulation during the measurements to prevent them from falling asleep. The first negative wave was measured and the p resence /absence of waves at longer latencies was also noted. The responses detected ranged from 1 to 10/zV. In six healthy control subjects
Table 1 Characteristics of the 20 subjects with neurodevelopmental impairments of various etiologies
Age Sex Medication Et iology/ Cerebral (years) ( m / f ) age of onset palsy
1 21 m CLB + PHT Immersion at 3 yrs Spastic tetraplegia 2 8 f CLB + PB + VPA Prematurity with asphyxia and IVH Mixed tetraplegia 3 18 f CLB + VP A Unknown with multiple anomalies Dystonic tetraplegia 4 10 f CBZ + DZP + VPA Unknown with congenitalhydrocephaly and optic atrophy Spastic tetraplegia 5 12 f CLB + PHT Unknown with West syndrome Mixed tetraplegia 6 21 f PHT + VP A Unknown with West syndrome Dystonic tetraplegia 7 19 f CBZ + CLB + VPA Partial trisomy of chromosome 13 Spastic tetraplegia 8 21 f CBZ + CZB + VPA Rett syndrome 3 yrs Spastic tetraplegia 9 13 f CZP + DZP + VPA Cardiac anomaly; asphyxia at 4 weeks Spastic tetraplegia
10 18 m CBZ + VPA Prematurity meningitis perinatally Spastic hemiplegia 11 43 m CBZ + PB + VP A Meningitis at 18 months Spastic hemiplegia 12 14 m CZP + VP A Unknown with West syndrome Mixed tetraplegia 13 15 m CBZ + CLB Haemolysis with respiratory arrest at 6 weeks Dystonic tetraplegia 14 45 m CBZ + VPA Encephalitis at 15 months Spastic hemiplegia 15 38 m PHT + CZP + VP A Prenatal t rauma and contusion at 10 years No 16 30 m CBZ, PHT Unknown with multiple anomalies No 17 9 f CZB + VPA Tuberous sclerosis 2 years No 18 44 f CBZ + PB Unknown, 2 years No 19 38 m CZB + PHT Encephalitis at 4 years No 20 24 m CBZ + PB + VP A Unknown with West syndrome Mixed tetraplegia
CBZ, carbamazepine; CLB, clobazam; CZP, clonazepam; DZP, d iazepam/n i t razepam; PB, phenobarbital; PHT, phenytoin; VPA, valproate sodium; IVH, intraventricular hemorrhage.
34 L. Leinonen et al. /Bra in & Det,elopment 1994; 16:32-9
(aged 23-49 years), who were studied under the same conditions, the peak latencies of the first negative wave at 70 dBnHL ranged from 70 to 94 ms; the peak latencies of the positive wave around 200 ms ranged from 140 to 226 ms. These values are in accordance with normative adult data obtained with such stimuli [17-19]. At the age of 8-10 years the latency of the first negative peak is within or near the adult range [20], in younger children the latencies are longer. We used 120 ms as the upper time limit for the normal first negative peak; all children with recordable responses, aged 9-15 years, had their response latencies within this range.
2.4. Visual evoked potentials (VEP) Responses to pat terned red LED flashes at 1 Hz
(given with the goggles of the measurement device), led separately to the right and left eye, were recorded with the following four derivations: Oz-Cz, Cz-nasion, Cz-4 cm to the left from Cz, supraorbital-outercanthus (measurement band 1-100 Hz; analysis time 500 ms 2-3 repeated averages from 200 responses). Blinks were rejected with the electrodes around the left eye. In all subjects a vertex negative wave peaking around 50 ms (44-65 ms) was recorded in the derivation Cz- nasion. It was regarded as the retinal b-wave which is suggested to derive from neural processing preceding the the ganglion cell activation [21]. Cortical potentials were measured from Oz-Cz and they ranged from 1 to 12 /~V. The latencies of the first occipitally negative peaks were determined and the p re sence /absence of waves at longer latencies was noted. Most of the sub- jects capable of a behavioral response enjoyed the stimulation (smiling, laughing, stopping all activities); one subject showed signs of aversion with rapid habitu- ation, however. Six healthy subjects of 10-49 years were also studied. In them the retinal responses were obtained at 48-57 ms latencies. Regardless of whether the eyes were open or closed, the first occipitally negative waves peaked at 63-95 ms latencies and the response sequences continued throughout the mea- surement period. The latencies, 63-95, ms are in line with normative data on the latencies of the first two negative waves for flash stimuli (less than 100 ms in both adults and children after the age of 4 years [22]). The latency of 100 ms was used here for both adults and children as the upper time limit of the normal first negative peak.
2.5. Somatosensory evoked potentials (SEP) Somatosensory evoked potentials were elicited by
stimulating alternately the right and left median nerves at the wrist (0.2 ms pulse at 2 Hz; electrodes at C 3 ' / C 4 ' (2 cm posteriorly to C3 and C4) and refered to Fz; passband 1 Hz-1 kHz; analysis time 200 ms; repeated averages of 200-500 responses). Stimulus in-
tensity was adjusted to produce a clear movement of the thumb. The latencies of the first negative peaks were determined and the p re sence /absence of waves at longer latencies was noted. Responses detected ranged from 0.5 to 10/xV. In studies on healthy adults the first negative peaks have been obtained at latencies less than 23 ms [22]. Within the age range of our subjects, 8-45 years, the latencies depend primarily on the height of the subject [22]. We used the following normative criteria for subjects with different heights: 170-179 cm N < 23 ms; 160-169 cm N < 22 ms; 150- 159 cm N < 21 ms; 140-149 cm N < 20 ms; 130-139 cm N < 19 ms.
When cortical SEPs were not detected, an addi- tional measurement was made in which peripheral responses were simultaneously recorded on two chan- nels (an electrode at the cervical spine, 7th spinous process, refered to an electrode at manubrium sterni; and Fpz, analysis time 100 ms). This was not routinely done because of predicted problems with E M G arte- facts from the neck musculature. The responses at the spinal nerve roots and the distal dorsal column path- ways were obtained in all subjects without cortical SEPs.
None of the subjects showed aversion to the electri- cal stimulation; most of them did not react to it at all. Intermittent auditory and visual stimulation was needed to prevent many subjects from falling asleep.
2.6. Behavioral studies The communication sampling procedure was de-
signed to elicit: like, dislike, wanting and rejection [23]. In addition, observations were made on the subjects' reactions to human contact and voice, and reactions to familiar or unfamiliar person. Each subject was video- taped twice, with a familiar adult (own caretaker) and with an unfamiliar adult (examiner); these sessions lasted about 30 min each. Also, those who were not tube fed were videotaped in a meal-time situation. In addition, the caretakers were interviewed with a struc- tured inventory to obtain everyday observations on the subjects' communicative behavior. The results of the behavioral study are not reported here in detail.
All subjects were also neurologically examined. The results of the behavioral and neurological testing, made by different investigators, agreed upon the behaviors described here. Some behaviors of forebrain origin, with high communicative significance, were selected, and the subjects were evaluated in terms of p r e sence / absence of these behaviors (Table 3). 'No communica- tive behavior' , descriptively used in Results, included: no differential responses to voices or faces, and no behavior aimed at establishing or avoiding visual-audi- tory contact with other people.
Due to cerebral palsies (Table 1), ten of the subjects could not walk and seven of them could not use their
L. Leinonen et al. / Brain & Development 1994; 16." 32-9 35
arms or fingers for reaching or grasping (Subjects 1,2,4-8). Such motor deficits greatly reduced their pos- sibilities for communication. All subjects showed, how- ever, facial expressions, they vocalized and blinked in response to certain stimulation. The subjects without learned motor skills (Subjects 1,2,4-7) were observed to detect stimulus conditioning or instrumentalization of some inborn responses (blinking, orienting move- ments of the eyes and head, smiling, vocalization). Stimulus conditioning had taken place (subjects 4-7) but instrumentalization of inborn reactive responses was not encountered.
None of the subjects had been deprived of social interaction. Even those with severe tetraplegia were daily carried to a living room and they had frequent contact with different personnel groups of the institute. The significance of the institutionalized living condi- tions for the presence/absence of the behaviors used as indices of forebrain functions observed (Table 3) was considered negligible.
2.7. Statistical testing The results of the evoked response studies were
compared with six behavioral indices of forebrain func- tion. Kruskal-Wallis test and multiple comparisons of Dunn were used for the statistical analysis of the comparisons.
3. RESULTS
No cortical VEPs, AEPs, or SEPs were detected in two subjects (Table 2, Fig. 1A). In these subjects the spontaneous EEG was extremely abnormal, too. Dur- ing waking, one of them had an EEG with frontal spike-wave complexes at 0.5-1.5 Hz without any other activity, and the other a monotonous rhythm around 13 Hz (Table 2). The evoked potentials shown in Fig. 1A are from a subject with absent background rhythms. The smooth appearance of traces C3'/C4'-Fz in the SEP record is due to the absence of high-frequency EEG and EMG noise; a similar result was obtained when the measurement was repeated on another day. No behavior of neocortical origin was observed in the subjects with absent cortical responses (Table 3). No positive emotional facial expressions, indicative of fore- brain limbic functions, were observed either.
In three subjects (Subjects 3-5) cortical evoked po- tentials were detected only in one or two of the modal- ities examined (Table 2). The forebrain functions of these subjects were rudimentary: looking at faces or one's own hands without changes in facial expression (Subjects 3,5) or in other behavior, opening the mouth when approached with a spoon, and avoiding the spoon after aversive taste by turning the head to the side (Subject 3), or reactive smiling at stroking of the trunk
T a b l e 2 VEPs, AEPs, SEPs and the quality of the background EEG in the 20 subjects
S u b j e c t s V E P l a t e n c i e s (ms) A E P l a t e n c i e s (ms )
I S u b j e c t s w i t h m i s s i n g r e s p o n s e s
1 . . . . . . . . . 13
2 . . . . . . . . . . + +
3 - + - - + . . . . 3 - 3 -
4 - - - + - - + + - 4 - 5 +
5 + + + - - - + + + 3 - 4 +
I I S u b j e c t s w i t h m i s s i n g o r m a r k e d l y d e l a y e d r e s p o n s e c o m p o n e n t s
6 - + - - + - + + - 3 - 4 -
7 - + - + + + + + - 4 - 5 +
8 + + - + - - - + + 1 - 3 + +
9 - + + + + + + + + 4 - 5 +
1 0 - + + + + + + + - 5 - 6 +
11 + + + + + - + + - 4 - 6 -
12 + + + + + - + + + 2 - 5 -
13 + + + + + + - + + 3 - 5 +
14 + + + + + + - + - 4 - 5 -
15 + + + + + + - + + 8 - 9 +
I I I S u b j e c t s w i t h r e s p o n s e c o m p o n e n t s a t n o r m a l l a t e n c i e s
16 + + + + + + + + + 5 - 8 -
17 + + + + + + + + + 3 - 6 +
18 + + + + + + + + + 5 - 6 +
19 + + + + + + + + + 6 - 7 +
20 + + + + + + + + + 4 - 6 -
T h e p r e s e n c e o f t he f i r s t o c c i p i t a l l y n e g a t i v e V E P peak , v e r t e x - n e g a t i v e A E P p e a k , a n d p a r i e t a l l y n e g a t i v e S E P p e a k is i n d i c a t e d in t h e f i r s t t i m e
w i n d o w , t h e l a t e r w i n d o w s d e t e c t r e s p o n s e s o f e i t h e r po l a r i t y . E E G r h y t h m is g i v e n in H z a n d sw i n d i c a t e s e i t h e r i n t e r m i t t e n t ( + ) o r c o n t i n u o u s
( + + ) s low s p i k e a n d w a v e ac t iv i ty . T h e s u b j e c t s a re g r o u p e d a c c o r d i n g to t he d e g r e e o f e v o k e d p o t e n t i a l p a t h o l o g y .
36 L. Leinonen et al. /Brain & Det,elopment 1994; 16:32-9
without differential responses to visual or auditory stimuli of different qualities (Subject 4; Table 3).
Slight deviations from the norm were observed in ten subjects (group II Table 2, Fig. 1B). As deviations were regarded as delayed latencies, or absence of vi- sual N < 100 ms, auditory P < 120 ms, and somatosen- sory N < 19-23 ms, and absence of potentials at two later time windows (Table 2). Two of these subjects (Subjects 6,7) showed no communicative behavior, whereas all others did. Due to the diversity of the response abnormalities, their behavioral significance could not be studied with the small number of subjects.
The cortical evoked potentials of five subjects ap- peared normal (group III in Table 2, Fig. 1C). All these subjects mastered a great variety of communicative skills. The peak latencies of the first cortical waves were normal in seven subjects: the somatosensory N < 19-24 ms varied from 16.8 ms to 22 ms (the heights of the subjects were 141-172 cm), visual N < 100 ms from 51 to 84 ms and auditory P < 120 ms from 71 to 94 ms. Communicative forebrain functions were observed in all of them (Table 3).
When group I (subjects with missing responses in at least one modality), II (subjects with delayed or missing response components), and III (with normal response pattern) were compared with each other with regard to the number of forebrain functions listed in Table 3, group I differed from groups II and III in a statistically significant way (Kruskal-Wallis test and multiple com- parison of Dunn: P < 0.05 and P < 0.01); whereas the
difference between group II and III was insignificant. When a similar comparison was made separately for visual, auditory, and somatosensory potentials, subjects with missing responses (only three subjects in each case) differered in a statistically singificant way only from the subjects with normal response patterns (P < 0.02 for all three modalities).
Responses to l-kHz tones were measured at two repetition rates, first at 0.5 Hz and immediately there- after at 2 Hz. In 13 of our 15 subjects with identifiable N < 120 ms, the responses decreased with increasing rate of stimulation. In subject 13 with an anoxic injury, the responses at 2-Hz repetition rate were higher than at 0.5 Hz repetition rate (4 ~V vs. 2 /xV), in subject 8 with Rett syndrome the resposes were of the same, rather high, amplitude (8 /xV).
4. DISCUSSION
A great variety of evoked potential deviations was observed in the 20 subjects studied, ranging from nor- mal responses to the absence of responses. This was expected considering the great diversity of symptoms and etiologies. In two subjects no cortical VEPs, AEPs or SEPs were detected. The somatosensory and audi- tory evoked brainstem potentials were, however, pre- served in them. The absence of cortical potentials was thus probably due to damage of the forebrain, either at the cortical or subcortical level. As expected, no behav-
Table 3 BehaL'ioral responses of forebrain origin elicited by t:isual, auditory, somatosensory, and gustatory stimuli
Subjects Smiling Looking Reaching Differentiated Words Speech at with hand responses to or other with faces or a n d / o r voices learned sentences
objects approaching gestures
Group I
1 2 3 4 + 5
Group II 6
7 8 + 9 +
10 + 11 + 12 + 13 + 14 + 15 +
Group III
16 + 17 + 18 + 19 + 20 +
÷ - -
÷ . . . .
÷ - - _ _
÷ - - _ _
+ - - + - -
+ + + - - _
+ + + + - -
+ + + -+- +
+ + + + - -
+ + + - - _
+ + + + - -
+ + + + +
+ 4- + +
+ + + + - -
+ + + + +
+ + + + +
+ + + + - -
L. Leinonen et al. / Brain & Deuelopment 1994; 16:32-9 37
ior of forebrain origin was observed in the subjects with absent cortical potentials. Absent responses in one modality were encountered in three subjects; they had some, although no communicative, behavior of forebrain origin. Five subjects with normal response sequences mastered many communicative skills. Devia- tions in the response patterns (missing or delay of some response components), observed in 10 subjects, did not relate to the degree of the communicative disability. The results are in line with the supposition drawn from studies on acute brain injury: bilateral absence of cortical SEP, VEP and AEP corresponds to the absence of forebrain functions needed for social
interaction. On the other hand, some cortical poten- tials can be recorded in many subjects with severe communicative disability.
Our two subjects with no cortical evoked potentials and no behavior of forebrain origin had histories of anoxic/ ischemic brain damage. SEPs were absent in one subject with chromosomal abnormality, and VEPs could not be elicited in two subjects with anoxic/ ischemic lesions and in one subject with congenital hydrocephalus and optic atrophy of unknown etiology. AEPs were not detected in one subject with unknown prenatal cause of the disorder. The findings are in accordance with the suggestion that the absence of
~" " I '# ~ ~ ~ w " w ~ "~ ,v ,~ ;v " ' ~ ~, J |,,. N14 "~
I z-~ C3"-FzJ ~ ~ ~ J ~ - - - - ~
~= ~ ~ . _ ~ _ ~ " ~ " = = ~ C 4 - . F z ~ - ~ . ~ - - = ~ -
1 0 0 m s ' stimulus
V E P
A E P
B. d e v i a n t r e s p o n s e s
i . . . . . . . .
•
~ , ~ ? , ~ , ~ .~., ~ ~,~-
C. n o r m a l r e s p o n s e s
"X
, U X,~
Fig. 1. Evoked potentials of three subjects: subject 2 with absent (A), subject 11 with deviant (B), and subject 18 with normal cortical sensory evoked potentials (C). Responses to flashes to the right eye are shown on the first row (VEP), responses to binaurally presented tones on the second row (AEP), and responses to stimulation of the right median nerve (A) and alternating stimulation of both median nerves (B,C) on the third row (SEP). Two averages of 200 responses and their means are shown in each derivation. The VEPs in B and C appear normal: the first occipitally negative peaks have normal latencies and the responses continue throughout the measurement period. The retinal b-wave (preceded by a-wave of opposite polarity) are seen in Cz-na derivation in A, B and C. The AEPs in B and C have normal latencies. In B there is only one negative wave, in C a positive wave around 150 ms is also present. SEPs in C appear normal, in B the latency of the first negative wave is delayed and stimulation of the right median nerve elicits no response (the subject is hemiplegic). In A with no cortical SEP the potentials of subcortical origin are normal: in derivation C7-st (cervical sp ine-manubr ium sterni) the first positive wave derives from the plexus, and the first negative wave originates in the nerve roots and distal parts of the dorsal column pathway; the prominent negative wave peaking at 14 ms in derivation Fpz-c 7 (cervical spine) originates in the brainstem.
38 L. Leinonen et al. /Bra in & Det~elopment 1994; 16:32 9
cortical sensory evoked potentials is a sign of severe forebrain failure, irrespective of the etiology of the condition.
The subjects with absent VEP were also behav- iorally blind, whereas all subjects with VEP responded to visual stimuli. This observation is in line with that of Frank et al. [24]. They found no VEPs in 30% of their 60 behaviorally blind children with normal eyes; in the rest the VEPs were abnormal. Thus, the absence of VEPs seems to be associated with behavioral blindness. On the other hand, recordable VEPs do not exclude behavioral blindness.
Sandman and Barron [25] obtained AEPs in all of their 39 severely or profoundly retarded subjects. This agrees with the present study: AEPs can usually be recorded in profoundly retarded subjects. In healthy subjects the amplitudes of AEPs decrease with de- creasing inter-stimulus interval between 7 and 0.5 s [26]. A normal decrease of response amplitude with increasing rate of stimulation was observed in 13 of our 15 responding subjects. This response characteristic seems thus to be resistant to cerebral tissue damage.
Degenerative encephalopathies may lead to a corti- cal response failure before death. In infantile neuronal ceroid lipofuscinoses, SEPs and VEPs are abolished at 2-3 years of age [27]. The behavioral deterioration is related to attenuation of evoked potentials and sponta- neous EEG, but forebrain reactions, like smiling when hearing familiar voices, can be preserved after the loss of evoked potentials (Santavuori, personal communica- tion). Our three subjects with progressive en- cephalopathies, one of unknown etiology, one with tuberous sclerosis and one with Rett syndrome, showed some communicative behavior and had preserved evoked responses in all three modalities.
More than half (32 of 50) of the evoked potentials detected in the 18 subjects were deviant. The interpre- tations of the deviations are problematic because sev- eral characteristics other than the local brain disorders distinguished our subjects from healthy ones. Move- ments and spasticity during the recordings increased EMG noise, and EEG noise was increased due to paroxysmal discharges. Evoked potentials can, how- ever, be recorded even during EEG discharges ([28]; our observation in one subject with rather continuous spike-wave activity). The level of alertness varied in our subjects more than in healthy persons. Deforma- tions of the brain may affect the potentials by changing the location and orientation of the source currents. The latencies of SEPs increase linearly with height, which cannot be accurately determined in subjects with severe deformities of the spine and limbs.
Anti-epileptic medication may also modify the re- sponses [14-16]. At therapeutic levels the changes, prolongation of latencies and attentuation of the wave- forms are, however, small or absent. The effects of
maximal non-lethal doses of nine anti-convulsants on the BAEPs in rat suggest that phenytoin and carba- mazepine are the most likely drugs to induce some changes [29]; phenytoin was the only drug which re- versibly abolished the responses. All subjects of the present study received two or three anti-epileptics. Both normal and deviant responses were recorded in the fifteen subjects receiving phenytoin or carba- mazepin. The only subject receiving both phenytoin and carbamazepin had normal SEP, VEP and AEP. The results suggest that the effects of anti-epileptics were small or neglible in comparison to the effects of brain lesions.
Behavior was assessed by the presence/absence of certain behaviors of forebrain origin, e.g 'reaching with arm'. Reaching under visual (or auditory) guidance is a sign of forebrain function, but is it justified to regard the absence of this behavior as a sign of forebrain failure? There might be a pyramidal tract lesion caudal to the forebrain (the 'locked-in' syndrome). That there were no such cases among our subjects was suggested by the preservation of functions in brainstem motor centers and pathways (expressed e.g. by positive Babin- ski's sign, coordinated eye movements, chewing and swallowing, orientating head movements; by aversive responses to some gustatory, auditory or somatosen- sory stimuli; and by spontaneous arm movements of forebrain origin).
In conclusion, the results agree with other studies on the significance of the absence of cortical SEPs, VEPs, and AEPs in predicting severe forebrain failure. Evoked response measurements thus aid the recogni- tion of subjects who do not benefit of rehabilitation.
ACKNOWLEDGEMENTS The authors thank Dr. Seppo Autio, the head of Rinnekoti Institute for Mentally Retarded, for support and interest in the study. The skill and patience of Mrs. Aliisa Sinivaara, the EEG technician of the institute, were critical for the success of the neurophysiological measurements. We also thank Dr. Maija-Liisa Laakso for advice in the statistical testing, and Dr. Kimmo Sainio for critical comments on the manuscript. The study was supported economically by Rinnekoti Research Foundation.
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