Longitudinal study of EEG and evoked potentials in neurologically asymptomatic HIV infected subjects

Electroencephalography and clinical Neurophysiology, 86 (1993) 145-151 © 1993 Elsevier Scientific Publishers Ireland, Ltd. 0013-4649/93/$06.00

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EEG92055

Longitudinal study of EEG and evoked potentials in neurologically asymptomatic HIV infected subjects B a h m a n Jabbari a,b Michael Coats a A n d r e s Salazar b5 A l e x Martin c5 Barbara Scherokman b and W e n d y A. Laws d a Division of Clinical Neurophysiology, Neurology Service, Walter Reed Army Medical Center, Washington, DC (USA), b Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD (USA), " Laboratory of Clinical Science, NIMH, Bethesda, MD (USA), and d H.M. Jackson Foundation, Bethesda, MD (USA) (Accepted for publication: 12 October 1992)

Summary

Serial electroencephalograms (EEGs) and multimodality evoked potentials (EPs) were performed along with neurological and neuropsychological evaluation, cerebrospinal fluid assessment and magnetic resonance imaging at 6 month intervals in 73 neurologically asymptomatic HIV infected subjects. The results were compared with 50 age- and sex-matched controls. EEG was abnormal in 2 subjects (3%) initially and was abnormal in 7 (9%) subjects by the last examination. EEG abnormality (diffuse slowing) correlated significantly with slowed reaction time in neuropsychological testing (P < 0.05). VEP and BAEP provided low yields of 1.3% and 4% respectively. SEP was abnormal in 7 (9%) of the subjects initially and in 10 (13%) subjects by the last testing, with 80% of the abnormalities seen on the posterior tibial study. In 3 subjects, initial SEP abnormalities predicted later development of myelopathy and peripheral neuropathy. Event-related auditory evoked potentials were performed in 39 subjects. They were abnormal in 5 subjects initially (12%) and in 6 subjects (15%) by the last examination and more commonly in advanced stages of the illness with lower T4 counts. This data shows the evolution and association of electrophysiological abnormalities in early HIV infection and suggests a predictive value for SEP in HIV infected asymptomatic individuals. Key words: HIV infection; AIDS; Electrocephalogram; Evoked potentials; Asymptomatic subjects

Acquired immunodeficiency syndrome (AIDS), a global h e a l t h p r o b l e m , is a m a j o r c a u s e o f d e a t h a m o n g ages 2 5 - 4 4 in the U n i t e d S t a t e s ( J a n s s e n et al. 1989). A p p r o x i m a t e l y 50% o f A I D S p a t i e n t s d e v e l o p n e u r o logical c o m p l i c a t i o n s a n d 80% disclose n e r v o u s system lesions on p o s t m o r t e m ( D e G i r o l a m i et al. 1990). F r e q u e n t c e r e b r o s p i n a l fluid ( C S F ) a n d m a g n e t i c reson a n c e i m a g i n g ( M R ) a b n o r m a l i t i e s f o u n d in asympt o m a t i c H I V i n f e c t e d subjects i n d i c a t e early involvem e n t o f t h e c e n t r a l n e r v o u s system ( D e la P a z a n d E n z m a n n 1988; M a r s h a l l et al. 1988; M c A r t h u r et al. 1988). M o r e t h a n h a l f o f A I D S p a t i e n t s d e m o n s t r a t e abnormal electroencephalograms (EEGs) or evoked p o t e n t i a l s (EPs) ( G a b u z d a et al. 1998; H e l w e g - L a r s e n et al. 1988). In n e u r o l o g i c a l l y a s y m p t o m a t i c H I V in-

Correspondence to: Dr. B. Jabbari, Neurology Service, Walter Reed Army Medical Center, Washington, DC 20307 (USA). Tel.: 202-576-0103; Fax: 202-576-2478. * The opinions or assertions expressed herein are those of the authors and are not to be construed as reflecting the views of the U.S. Army, Department of Defense or Uniformed Services University of the Health Sciences.

f e c t e d subjects, s o m e a u t h o r s have r e p o r t e d f r e q u e n t E E G a n d E P a b n o r m a l i t i e s suggesting a m a n a g e m e n t role for t h e s e tests in this d i s o r d e r ( K o r a l n i k et al. 1990; S o m m a - M a u v a i s et al. 1990). In contrast, o t h e r s have r e p o r t e d no E E G a b n o r m a l i t i e s ( G o o d i n et al. 1990). W e p r o s p e c t i v e l y s t u d i e d serial E E G s a n d E P s in n e u r o l o g i c a l l y a s y m p t o m a t i c H I V i n f e c t e d subjects in o r d e r to a n s w e r the following questions: H o w o f t e n a r e E E G s o r E P s a b n o r m a l in this p o p u l a t i o n ? C a n early E E G a n d E P a b n o r m a l i t i e s p r e d i c t o c c u r r e n c e of l a t e r neurological complications? Do EEG or EP abnormalities c o r r e l a t e with n e u r o l o g i c a l , n e u r o p s y c h o l o g i c a l o r M R a b n o r m a l i t i e s ? P r e l i m i n a r y d a t a on t h e s e p a t i e n t s ' n e u r o l o g i c a l , n e u r o p s y c h o l o g i c a l a n d m a g n e t i c reson a n c e imaging e v a l u a t i o n s have b e e n r e p o r t e d elsew h e r e ( C o a t s et al. 1990).

Materials and methods T h e study g r o u p c o n s i s t e d o f 73 n e u r o l o g i c a l l y a s y m p t o m a t i c H I V s e r o p o s i t i v e individuals. A l l subjects signed an i n f o r m e d c o n s e n t a n d a g r e e d to have

146

repeated testing at 6 month intervals. The test battery included a neurological examination, a 6 h neuropsychological evaluation, magnetic resonance imaging (MR), lumbar puncture, E E G and EPs. There were 68 males and 5 females with a mean age of 32 years (range: 22-44). We defined the subjects' clinical status according to the Walter Reed Classification (Redfield et al. 1986). Most of the subjects (57%) belonged to stages I-II, i.e., seropositive with or without lymphadenopathy (stage I of CDC classification). T4 cells ranged from 3 to 1489 (mean 460). Fifty-three percent of the subjects complained of occasional headaches and 50% of irritability, both of which tended to decrease with time and did not differ from seronegative controls with depression or adjustment disorders. Subjects were screened for opportunistic infections and those who had it were excluded from the study. The screening procedure consisted of clinical examination and CSF assessment of fungal antigens as well as cultures. No subject was on Zidovudine (AZT) on initial evaluation. Twenty-six subjects (35%) received treatment with AZT subsequently during the 2 year course of this study. EEGs were performed on 18- and 21-channel equipment using the international 10-20 system of electrode placement. Hyperventilation and photic stimulation were routinely performed; sleep was recorded in 80%. Abnormal patterns were defined according to current E E G standards (Niedermeyer and Lopes da Silva 1987; Daly and Pedley 1990). Each subject had visual (VEP), brain-stem auditory (BAEP), and somatosensory (SEP; median and posterior tibial) evoked potentials. The VEP stimulus was a TV-generated checkerboard pattern with a visual angle of 34.5 min and a reversal rate of 2.1/sec. The test was performed in a semi-dark room with constant screen luminance. The amplifiers had a filter band of 1-100 Hz. Two trials of 200 averaged response were obtained. Brain-stem auditory evoked potentials (BAEPs) were recorded at Cz on two channels simultaneously, referred to ipsilateral and contralateral ear lobes. The stimulus was a 10.1/sec click sound delivered at 65 dB SL to the tested ear, while the non-tested ear was masked with white noise. The filter band was 100-1500 Hz. Two trials of 2000 averaged responses were obtained. The SEP stimulus was a 100 /zsec square wave constant current electrical pulse. The recording was performed in a quiet semi-dark room and the subject was encouraged to relax. No sedation was used. The median nerve was stimulated at the wrist and the posterior tibial nerve at the ankle at 5.1/sec and 2.1/sec respectively. The stimulus intensity was slightly above motor threshold producing rhythmic thumb or foot movements. Median responses were recorded from Erb's point, C6 cervical level and contralateral so-

B. JABBARI ET AL.

matosensory scalp region (Cc) with Fz and ear lobe references. Posterior tibial EPs were recorded at the level of popliteal fossa (PF) and L1 vertebra (N22) (referred to the iliac crest) and at scalp Cz, 2 cm behind Cz (referred to Fz) and between C3 and C4 scalp locations. The amplifier bandpass, for both median and posterior tibial SEPs, consisted of 10 low cut-off and 3000 high cut-off. Each study included two trials averaging 10001500 times for the median and 800-1000 times for the posterior tibial test. VEP, BAEP and SEP results were compared with those of 50 age- and sex-matched asymptomatic HIV seronegative controls (48 males, 2 females, mean age 33 years, range 20-47 years). Event-related auditory evoked potentials (ER-AEPs) were obtained randomly in 39 subjects. We used tones of 65 dB SL with 50 msec duration and rise and fall times of 5 msec, delivered at a rate of 0.7/sec binaurally. In 86% of the trials the tone had a pitch of 1000 Hz (frequent tone) and on 14% of the trials it had a pitch of 2000 Hz (rare tone). The amplifier band width was 1-35 Hz. Responses were recorded and mapped on Biologic equipment from 16 scalp locations (10-20 system) referred to linked ears. N1, P2, N2 and P3 components were identified and their latencies were measured according to the methodology of Goodin et al. (1990). Results were compared with those of 20 seronegative asymptomatic subjects. VEP, BAEP and SEP were considered abnormal when they demonstrated one or both of the following: (1) absence of the obligatory wave forms - - P100 of VEP, waves I, III or I V - V complex of BAEP and Erb, P/N13, N20, PF, P40 of SEP and P3 and N1 components of ER-AEP; (2) increased conduction times or interpeak intervals (beyond 3 S.D.) individually or side to side differences. The electrophysiological data were interpreted by one board-certified electroencephalographer blinded to the subject's clinical state or laboratory data (infected versus control, CSF or MR findings). MR was performed on a 1.5 Tesla GE scanner. T1, T2 and balanced images were obtained at 5 mm intervals in standardized horizontal section. Studies were interpreted by a neuroradiologist blinded to the subjects clinical status and electrophysiological findings. The neuropsychological test battery consisted of standard and experimental measures of information processing speed, attention and concentration, estimated general intellectual functioning, learning and memory, language skills, visuo-spatial and constructive ability, and executive function. In the present report, neurophysiological measures were compared with neuropsychological reaction time measures (simple and choice) of cognitive and motor speed. For the simple reaction time task, the subjects were required to press a centrally positioned lever at the presence of a blue light. Choice reaction time required the same response

EEG AND EP IN HIV INFECTED SUBJECTS

147

to a blue light for 50% of the trials, with inhibition of the response to a red light presented 50% of the time. Presentation of the red or blue light in the choice reaction time condition occurred randomly. Individual reaction time scores were significantly slowed if either the simple or choice (or both) conditions were > 2 S.D.s slower than age- and education-matched normal controls. Nineteen subjects reported for 1, 23 subjects reported for 2, 17 for 3, 8 for 4 and 6 for 5 testing sessions at 6 month intervals. Statistical analysis of the data was performed using the chi-square test with Yates' correction. For small numbers Fisher's 2-tailed exact test was used.

Results

The initial EEG was abnormal in 2 subjects (3%), both of whom showed diffuse slow activity. An additional 5 patients developed E E G abnormalities during the course of the study (Table I). Four of these also demonstrated diffuse slowing. The 5th subject developed frequent runs of 2-4 Hz slow and sharp activity over the right anterior temporal region concurrent with intermittent episodes of clouding of consciousness. His neurological examination and MR at this time showed no abnormalities. Treatment with phenytoin decreased the episodes. Five of 7 patients with abnormal EEGs (70%) demonstrated significantly slowed reaction time in neuropsychological examinations (Table I) compared to 15 of 66 (22%) patients with a normal E E G ( P = 0.02, Yates' corrected P = 0.048). MR disclosed extensive subcortical areas of increased T2 signal in 1 of 5 subjects. Four of the 7 patients with abnormal EEGs

had more advanced stages of the infection; two of them died. Pattern reversal VEP was abnormal in 1 patient (1.3%), demonstrating prolonged P100 latencies bilaterally. She had a normal MR and her neurological examination showed no evidence of visual system dysfunction. Initial BAEP was abnormal in 2 patients; both showed absence of wave I with a mild delay of waves II, III, IV and V, consistent with a peripheral cochlear disorder. Three patients (4%) developed a central pattern of BAEP abnormality during the course of the study. Of these, 1 subject showed absence of waves I I I - V bilaterally and 2 subjects demonstrated prolonged I - V interpeak latencies with well-formed wave I potentials. All 3 patients had normal hearing and their MR disclosed no brain-stem or posterior fossa pathology. Seven subjects demonstrated an abnormal SEP at first examination (9%) and 3 more developed an abnormal SEP during the course of the study. Eight of 10 had a normal median and abnormal posterior tibial study. One patient displayed abnormality of both median and posterior tibial SEP and 1 showed bilaterally abnormal median SEPs only. Three of 10 subjects displayed a peripherally abnormal SEP pattern characterized by loss of PF potential and delay of N22 and P40 components without increased central conduction time. Two of these gradually developed a clinically manifest peripheral neuropathy 6-12 months later with abnormal nerve conduction velocity tests. Of the remaining 71 subjects, only 1 disclosed a clinically manifest peripheral neuropathy over this period. Of 7 patients with a central SEP abnormality, 2 demonstrated loss of P40 potential (Fig. 1) and 5 showed prolonged

TABLE I Clinical, T4 count, EP, reaction time and MR findings in 7 subjects with abnormal EEG. Patterns of EEG Abnormality

Age

Stage (lst/last)

T4 count (lst/iast)

ER-AEP

Reaction time

MR

NL/AB NL/AB NL/AB

28 30 31

2/2 2/2 2/3

484/449 495/449 404/320

NL NL ABN

309/434 867/1053 610/758

NL 2 lesions, It frontal NL

NL/AB AB/AB NL/AB AB/AB

35 30 45 28

5/5 5/5 5/5 5/6

381/80 63/63 49/6 289/9

NL ABN NL ABN

476/654 412/567 342/423 487/544

NL NL Multiple lesions * Diffuse cortical atrophy

lst/last

Diffusely slow Diffusely slow Diffusely slow Paroxysmal sharp and slow, rt temp Diffusely slow Diffusely slow Diffusely slow

In the reaction time column, first number represents simple RT and second number choice RT.

Simple RT Choice RT

Mean

S.D.

Range

316 409

52 56

252-429 320-518

* Small subcortical areas of increase T2 signal; frontal, parietal and occipital.

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Fig. 1. A: SEP study of a 34-year-old seropositive subject shows absence of P40 potentials after stimulation of posterior tibial nerves. B: age-matched control subject showing well-formed P40 potential. Our subject, over a period of 18 months, developed a myelopathy, characterized by bilateral lower limb hyperreflexia, sustained ankle clonus and bilateral Babinski signs.

CCT (bilateral 1, unilateral 1, unilateral side to side difference 3). One of the 2 patients with absent P40 gradually developed increased tone in both legs with hyperreflexia bilateral sustained ankle clonus and bilateral Babinski signs. His cranial MR was normal. Spine MR disclosed no intra-axial pathology. There was a subtle thoracic disk at T6 with no cord displacement.

None of the other 52 subjects who had repeated SEPs disclosed clinical evidence of a myelopathy during the follow-up period. Event-related auditory EP (ER-AEP) was initially abnormal in 5 of 39 subjects (12%). One other subject developed abnormal ER-AEP during the course of the study. The pattern of ER-EP abnormality of these

TABLE II Clinical, T4 count, reaction time and MR correlates of 6 subjects with abnormal ER-AEP. Age

ER-AEP (P3/N2)

W.R. stage (lst/last)

T4 count (lst/last)

EEG

Reaction time (simple/choice)

MR

39

234/174 512/300 482/320 502/382 412/328 460/358 480/300 476/304 370/330 ABS/ABS 420/324

1/3

513/302

NL

307/347

2/3

404/320

Slow

727/803

Diffuse cortical atrophy, mild NL

3/3

230/240

NL

432/581

4/4

185/147

NL

391/417

Large subcortical lesions NL

NL

298/337

NL

Slow

488/544

Diffuse cortical atrophy, marked

31 32 43 31 28

5/5

69

5/6

289/9

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P3 N2

Mean

S.D.

RT

Mean

S.D.

Range

298.8 235.6

37.06 32.94

Simple Choice

316 409

52 56

252-429 320-518

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Fig. 2. Left posterior tibial SEP of a 30-year-old seropositive asymptomatic subject. A: initial study, neurological examination is normal. PF is a b s e n t a n d P 4 0 is d e l a y e d . S E P f i n d i n g s w e r e b i l a t e r a l a n d s t r o n g l y s u g g e s t i v e o f a c o n d u c t i o n non-obligatory

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subjects consisted of prolonged latency of P3 and N2 components. One patient with an initially normal P3 and N2 demonstrated no N2 and P3 in follow-up studies (Table II). Subjects with an abnormal ER-AEP had a lower mean T4 count compared to HIV positive subjects with normal ER-AEP (131 versus 436). Two of 6 subjects with an abnormal ER-AEP had an abnormal EEG (33%) compared to 3 of 33 (9%) subjects with normal ER-AEP. Neuropsychological examination disclosed slowed reaction time in 3 of 6 subjects with an abnormal ER-AEP (50%) and 7 of 33 subjects with normal ER-AEP (21%). Two of 3 subjects with an abnormal ER-AEP and a slow reaction time also had an abnormal, diffusely slow EEG (Table II).

Discussion

Human immunodeficiency syndrome produces a variety of neurological complications including aseptic meningitis, AIDS dementia (subacute encephalopathy), myelopathy, peripheral neuropathy and myopathy (Snider et al. 1983; Price et al. 1988; Kieburtz and Schiffer 1989). Significant cognitive deficits in AIDS conform to the pattern of subcortical dementia with predominance of white matter lesions, loss of myelin, and macrophage/microglial infiltration (Petito 1988).

n e r v o u s s y s t e m ( N 2 2 is a decrease

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neuropathy.

In one study (Gabuzda et al. 1988), 27 of 47 (57%) patients with AIDS or AIDS-related complex (ARC) demonstrated an abnormal EEG with intermittent or continuous diffuse slowing (65%), focal slowing (22%) and paroxysmal slow and sharp activity (11%). Approximately two-thirds of patients with AIDS dementia disclosed EEG or ER-AEP abnormalities (Gabuzda et al. 1988; Goodin et al. 1990). The yield of EEG in neurologically asymptomatic HIV seropositive subjects has reportedly varied from 0 to 30% (Goodin et al. 1990; Koralnik et al. 1990) (Table II). Nuwer et al. (1991) criticized the latter study for using an artificial abnormality scale which included patterns of doubtful significance, i.e., alpha amplitudes of over 70 ~V, excessive drowsiness, anterior spread of alpha and poor alpha reactivity. In our study the initial EEG was abnormal in only 3% and last EEG in 9% of the subjects. Abnormal EEGs were seen in the advanced stages of the infection and diffusely slow EEG associated significantly (P < 0.05) with slowed reaction time (Table I). In 1 patient with a normal initial EEG, a 3rd EEG 12 months later disclosed focal epileptiform abnormalities concurrent with newly developed complex partial seizures. ER-AEP was initially abnormal in 12% and then in 15% of our subjects by the last examination. These data agree with that of Goodin et al. (1990) (Table III)

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B. JABBARI ET AL.

in showing the sensitivity of E R - A E P to H I V infection. Abnormal E R - A E P s associated with slow E E G and slowed reaction time but the relationships did not reach statistical significance. P o s t - m o r t e m studies have shown a vacuolar myelopathy with significant demyelination of posterior columns (Petito 1988) in 30% of A I D S patients. In one study (Helweg-Larsen et al. 1988), PT-SEP of 23 patients with A I D S myelopathy showed prolonged central conduction times in 100%. SEP was abnormal in 10 of our subjects (13%), 7 of whom disclosed a pattern indicative of sensory disturbance in the central nervous system. Six of these 7 disclosed sole abnormality of posterior tibial SEP suggesting conduction defect in the spinal cord rather than supraspinal pathways. One of these subjects developed a myelopathy during the course of the study. Although his M R showed a mild thoracic disk, we do not believe this subtle disk with no cord impingement caused his SEP and clinical abnormalities. Peripheral neuropathy is a common and often early complication of AIDS. The clinical forms consist of a p r e d o m i n a n t l y sensory polyneuropathy, acute or chronic inflammatory demyelinating polyneuropathy, mononeuritis multiplex, and a sensory ataxic polyneuropathy due to ganglioneuritis (Fuller et al. 1991). Electromyography and nerve conduction velocity studies can disclose subclinical evidence of a peripheral neuropathy in asymptomatic seropositive H I V infected subjects (Dalakas and Pezeshkpour 1988). The SEP pattern of a mild peripheral neuropathy consists of amplitude reduction or absence of peripheral potentials ( E R B in M-SEP and PF in PT-SEP) with mild to moderate delay of central components. Three of our patients showed such a SEP pattern. Two of 3 developed a clinically manifest peripheral neuropathy after 6 and 12 months. SEP technology constantly evolves and improvement of the methodology adds to the yield of the procedure. Recently, N 9 / P 1 4 amplitude ratio abnormalities were found to be the most sensitive measure of SEP in demyelinating disorders (Garcia-Larrea and Maugui~re 1988). Since H I V infection often produces subcortical pathology, it would have been helpful to include N 9 / P 1 4 ratio assessment in our protocol.

Although tissue examination of A I D S patients discloses focal areas of myelin loss and microglial aggregation in the brain-stem, signs and symptoms referable to brain-stem are infrequently described. Three of our patients developed central BAEP abnormalities within 6 - 1 2 months of their first examination. In our view this finding represents subclinical disturbance of brain-stem auditory pathways. A similar BAEP abnormality was reported to improve in an H I V infected child after treatment with zidovudine (Brivio et al. 1991). Anecdotal reports of acute or progressive hearing loss suggest involvement of the middle ear or cochlea in H I V infection (Rarey 1990). In some cases syphilitic co-infection caused the cochlear damage (Smith et al. 1989). Two of our patients disclosed a peripherally abnormal B A E P on initial examination with mild sensory neural hearing loss. The relevance of this finding to H I V infection remains doubtful considering frequent exposure of the military population to acoustic trauma. Post-mortem and M R data of A I D S patients have not shown discrete optic nerve lesions. A I D S optic neuropathy often results from co-infection with cryptococcus, syphilis, cytomegalic or zoster-varicella viruses (Winward et al. 1989). Only one of our patients had an abnormal VEP. The VEP abnormality was characterized by bilaterally delayed P100 latency on initial examination. She had a diffusely slow E E G , a normal MR, and normal neurological examination. Our low V E P yield (1.3%) contrasts with that of 18% reported by another group of investigators (Somma-Mauvais et al. 1990). Part of this difference may be due to the fact that we used 3 S.D. rather than 2 S.D. as the criteria for V E P abnormality (Table III). The V E P pattern of our patients remained stable and did not change in any of the 53 patients who had follow-up testings. We did not study flash VEPs. There are reports of a delayed P2 component of flash VEP in global brain disease when pattern shift V E P discloses no abnormality (Cosi et al. 1982; Harding et al. 1985). In conclusion, these data show a higher yield for PT-SEP and E R - A E P in neurologically asymptomatic H I V infected subjects. E E G abnormalities gradually develop and associate with delayed reaction time, advanced stages of infection and unfavorable outcome. SEP may be predictive of peripheral neuropathy or

TABLE III EEG and EP results in HIV infected neurologically asymptomatic subjects. Studies Koralni et al. (1990) Goodin et al. (1990) Somma-Mauvaiset al. (1990) Jabbari et al.

Number 29 41 67 73

EEG 10 (30%) 0 (0%) 11 (10%) 2 (3%) 5 (9%)

VEP 0 (0%) . . 8 (18%) 1 (1.3%) 0 (0%)

BAEP 7 (23%) . . 4 (11%) 2 (3%) 3 (5.6%)

M-SEP 3 (10%)

PT-SEP -

4 (8%) 2 (3%) 0 (0%)

5 (7%) 3(5.6%)

ER-AEP (28%) 5 (12%) 1 (2%)

Comments EP ABN > 2 S.D. EP ABN > 2 S.D. EP ABN > 2 S.D. First test Follow-up*

* Fifty-three of 72 patients reported for more than one testing. The period of follow-up varied from 6 to 24 months (mean 11.8 months). Percentages in the follow-up line represent additional EEG and EP abnormalities observed during this period.

EEG AND EP IN HIV INFECTED SUBJECTS m y e l o p a t h y b u t c l a r i f i c a t i o n o f this issue r e q u i r e s s t u d y of a larger number of subjects and longer follow-ups. Electroencephalograms were performed by Army Sgt.'s James Freshour and Howard Mays. Evoked potentials were performed by Sgt. Michael Perkins. Mrs. Wendy Kosmatka typed the manuscript.

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