Brain (1990), 113, 49-63
BRAINSTEM AUDITORY EVOKED POTENTIALS AND SOMATOSENSORY EVOKED POTENTIALS IN PONTINE HAEMORRHAGE CORRELATIONS WITH CLINICAL AND CT FINDINGS by A. FERBERT, H. BUCHNER and H. BRUCKMANN (From the Department of Neurology, Medical Faculty RWTH, Aachen, FRG) SUMMARY Electrophysiological studies were performed on 17 patients with pontine haemorrhage. Most had had massive hypertensive bleeding, leading to death in 12 of them within 3 months. Of the 5 surviving patients, 2 had a poor outcome and 3 a moderately good outcome. Brainstem auditory evoked potentials (BAEPs) and somatosensory evoked potentials (SEPs) were recorded in all patients, mostly with serial recordings. BAEPs were pathological in all patients. The most important finding was a reduction in amplitude or loss of waves. With a loss of waves after wave II bilaterally all patients died; the 2 patients with a normal amplitude of waves I —V at least on one side, survived in good condition. Further prognostic conclusions were not possible. The correlation with the clinical state was limited and was best for small unilateral tegmental haemorrhages. Eleven of the 17 patients suffered bilateral loss of the N20 component of the median nerve SEP. All these patients died. In patients with unilateral loss of the SEP the outcome could be favourable even if the bleeding extended across the midline. 'Subcortical' SEPs were not significantly altered. EEG findings in 15 and visual evoked potentials in 4 patients showed preserved forebrain electrical activity even in patients in poor condition.
INTRODUCTION
Pontine haemorrhage still has a poor prognosis (Goto et al., 1980; Bewermeyer et al., 1984) and therapeutic measures are limited. However, the wide use of CT has shown that in some patients with less severe brainstem syndromes a small pontine haemorrhage can be detected. Before the advent of CT these patients may have been suspected of suffering from ischaemic brainstem infarction. Thus a few patients may survive after a pontine haemorrhage (Kase et al., 1980; Nakajima, 1983; Howard, 1986; Weisberg, 1986). Vascular malformations such as angiomas are more likely to produce smaller haemorrhages, whereas large haemorrhages are usually due to severe longstanding hypertension. CT can easily detect a pontine haemorrhage. However, no precise prognostic factors are known to exist except for the fact that larger haemorrhages have a worse prognosis than smaller (Masiyama et al., 1985). Evoked potentials have proved to be of Correspondence to: Dr A. Ferbert, Department of Neurology, Medical Faculty RWTH, Pauwelsstrasse, D-5100 Aachen, FRG. © Oxford University Press 1990
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prognostic value in other brainstem lesions. However, surprisingly few results of brainstem auditory evoked potentials (BAEPs) and somatosensory evoked potentials (SEPs) in patients with pontine haemorrhage are reported in the literature apart from single case studies (Stockard and Rossiter, 1977; Oh et ai, 1981; Chiappa, 1983; Hammond et al., 1985; Portenoy etal., 1985; Hashimoto, 1986). There has as yet been no study using SEP or BAEP or both in pontine haemorrhage with a larger number of patients. The purpose of this study was to investigate whether BAEP and SEP have prognostic value in pontine haemorrhage, and to correlate evoked potential findings with clinical signs and the localization of the haemorrhage by imaging techniques. P A T I E N T S AND METHODS We investigated 17 patients with pontine haemorrhage. All patients underwent CT and 4 also had MRI. Patients with cerebellopontine haemorrhages, and with purely midbrain or medullary bleeding, were excluded, but in some patients with large haemorrhages there was some extension from the pons into the midbrain. No considerable extension of a pontine haemorrhage into the medulla was observed. The average age of our patients was 51 yrs, with a range of 2 5 - 7 3 yrs. There were 12 males and 5 females. Twelve patients had suffered from severe hypertension for many years, but in 2 others hypertension was only discovered after the bleeding. Five had a previous history of alcohol abuse. One patient was being treated with warfarin and another had several metastases from a malignant melanoma. Twelve patients died within 3 months of the haemorrhage. One had a prolonged survival but had a tetraplegia and respiratory problems which required assisted ventilation. He died after 4 months. Another was at home but severely disabled, confined to a wheelchair, and spending most of his time in bed. He died 1 yr after his haemorrhage. In 3 patients there was only a slight to moderate neurological deficit with spasticity in all four limbs and ocular motor abnormality after 6 months. All patients underwent BAEP and SEP investigations with serial recordings (an average of 3.5 per patient). In addition, the EEG was recorded in 15 patients and visual evoked potentials (VEPs) in 4 patients. Most of the patients were being treated in the intensive care unit. A neurological examination was performed before any electrophysiological studies. However, the neurological examination was sometimes limited by the fact that many patients were receiving sedative drugs because of assisted ventilation. When the signal/noise ratio was low, drugs blocking neuromuscular transmission were used in artificially ventilated and sedated patients. Thus nearly artefact-free records could be obtained for most patients. BAEPs were elicited by monaural stimulation of an alternating polarity with 90—95 dB HL. This high click intensity was chosen as older patients often have badly defined waves I using lower click intensities because of high-frequency hearing loss. The effect of selective click stimulation with either rarefaction or condensation was only studied in certain cases. Stimulus duration was 0.1 ms and frequency 14.1 Hz. The contralateral ear was masked with white noise of 70—75 dB HL. Platinum needle electrodes were placed over the mastoids and the vertex. Ipsilateral and contralateral recordings were carried out simultaneously. A total of 2000 sweeps was averaged with bandpass filters at 150 and 3000 Hz, 6 dB/octave. Latencies of waves I, III and V and the interpeak latencies I - V , I —III, III—V, HI—V were measured and compared with normative data from our institute ( ± 2 . 5 SD). The amplitude ratio V/I was calculated and considered to be pathological if the value was smaller than 1. Even if this ratio may occasionally be smaller than 1 in young healthy adults using high click intensities of 9 0 - 9 5 dB HL, it was always above 1 in our normal subjects older than 40 yrs; 16 of our 17 patients were in this age group. Amplitude of wave I is much more prone to age-dependent amplitude reduction than wave V. An amplitude ratio of less than 0.5 for waves III/I was defined as pathological. SEPs after electrical stimulation of the median nerve at the wrist were derived simultaneously from the contralateral hand field (C3/P3 or C4/P4 according to the 10/20 system) and the lower spine (Cv7-Fz).
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In some cases, further montages were studied (Erb's point; C2-Fz; Cz-contralateral shoulder; Cv7-'jugulum\ i.e., anterior neck just above the sternum). The bandpass was 5—1500 Hz; 50-500 sweeps were averaged depending on the signal/noise ratio. Latencies of N13 of the 'spinal' potential and N20 were measured, as well as central conduction time between both peaks. An amplitude ratio N20/N13 of less than 1 and differences in amplitudes between the right and left cortical potentials of more than 50% were considered to be abnormal. The amplitude of the N20 potential was measured from the peak of N20 to the peak of P25. In those cases in which the N20 component was reflected in the Cv7-Fz derivation, the amplitude of N13 was measured from the peak to baseline. The EEG was recorded according to the 10/20 system and VEPs from Oz to Fz using monocular or binocular flash stimulation with light-emitting diodes. RESULTS
Brainstem auditory evoked potentials BAEPs were pathological in all 17 patients with pontine haemorrhage (fig. 1). The predominant BAEP finding was a reduction in amplitude or loss of waves, whereas increased latencies with normal wave amplitude was less common. In initial recordings, normal waves I—III were found in 7 patients (8 ears). In most cases waves IV and V could not be distinguished from each other and were reduced in amplitude or occasionally delayed in latency. In some cases latencies of this wave complex were even shortened, so that the impression given was that of an isolated loss of wave V with preservation of wave IV {see fig. 4, right ear stimulation; an IPL III —V of 1.2 ms with a normal IPL I—III of 2.3 ms has never been observed in our control subjects). This interpretation was supported by the fact that both waves could not be seen separately on the contralateral recording. There was only one case with a very broad IV/V complex of high amplitude (fig. 1, Case 7) and another patient with delayed waves IV and V (fig. 1, Case 16). Normal waves I, and sometimes also waves II, with pathological waves III —V were found in 11 patients (17 ears). In most of these patients wave HI was reduced in amplitude and waves IV and V were absent or could scarcely be seen. In addition to the latter group there were 3 patients (5 ears) in whom only wave I was preserved, and no waves thereafter (fig. 1, Case 10). All 3 patients displayed spontaneous respiration and other preserved brainstem reflexes. In Case 9 only some small waves were derived between 4 and 8 ms which could not be classified. In another patient, no BAEP could be obtained on either side, even at the initial recording. This patient was known to have had hearing loss before the haemorrhage, although he was not completely deaf. In 8 patients the BAEPs were significantly different on the two sides whereas no differences or only minor changes were observed for the other 9. Differences in latency, amplitude or wave form could even be observed when comparing wave I on the two sides of 6 patients (fig. 1, Cases 1, 3, 5, 8, 11, 13). Major differences of BAEP after different click polarities could be demonstrated in one patient (fig. 2). Rarefaction clicks evoked waves I—IV bilaterally. Although condensation clicks evoked 4 waves on the right and only 3 waves on the left, the result of alternating click stimuli showed only waves I and II on the left and waves I—IV
52
A. FERBERT AND OTHERS BAEP
A/V~-^~c W A A ^ —
FIG. 1. BAEP findings for all 17 patients with ponti haemorrhage at the initial recording. There was preexisting hearing loss in Case 17 (lowest panel). Cases 4, 14 and 16 made a good recovery and Cases 7 and 15 remained severely disabled. All other patients died within 3 months.
17
10 ms
on the right. This effect was produced by considerable latency differences of waves II —IV to rarefaction-condensation stimulation on the right, whereas such latency differences were not present on the left. The CT scan in this case showed extensive
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FIG. 2. Case 2, 45-yr-old hypertensive patient with tetraplegia, ocular bobbing and 'coma vigil', A, BAEPS with alternating clicks in the lowest line show only waves I and II on the right. With rarefaction (RAR) and condensation (CON) clicks 4 waves can be seen. Different latencies of waves HI and IV (V) after rarefaction and condensation lead to cancellation of these waves in the alternating mode. On the left the difference between rarefaction and condensation is even more pronounced. The third panel down shows the addition of panels I and 2 by computer; there is no difference from alternating stimulation, B, CT scans showing the pontine haemorrhage which spares the medulla oblongata and the midbrain.
bilateral bleeding with a slight preponderance to the right, sparing the most caudal part of the pons (fig. 2). An exact correlation between BAEPs and neurological findings could not be detected. Severe BAEP abnormalities were found not only in tetraplegic patients but also in patients with only a moderate tetraparesis (fig. 3). They were found in patients who reacted to command (e.g., by ocular lid movements) and also in comatose patients. In the patient with the small haemorrhage in the left caudal pontine tegmentum, a left nuclear facial paresis, a one and a half syndrome and right hemihypaesthesia and hemiataxia correlated well with normal waves I and II and severely altered waves III—V to the left ear stimulation (fig. 4). The significance of the additional loss of wave V on the right will be discussed later. All patients who displayed loss of potentials after wave II bilaterally died. Both patients with normal amplitudes of waves I—V at least on one side survived. However, in the other BAEP pattern the prognostic value was somewhat vague: some patients died and others survived. Two different types of change could be observed in BAEP serial recordings. In some patients the BAEP indicated a change in brainstem function, leaving wave I unchanged
A. FERBERT AND OTHERS B Median
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/ C47C3'-Fz t
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I
I
I
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I
I
i
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25
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25
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FIG. 3. Case 4, 25-yr-old patient with left facial paresis, dissociated downbeat nystagmus, horizontal gaze paresis, anarthria, and right hemiparesis. A, BAEPS showing normal waves I bilaterally and a normal wave III on the right with severe alteration thereafter. The main pathology is a reduction in amplitude. In the further course of the patient, indicated by the recording dates, there is a deterioration of the left BAEP despite clinical recovery, B, cortical SEPs are normal after left median nerve stimulation and absent on the contralateral side. There is some reduction in amplitude of the left median nerve SEP in the further course of the patient. Normal 'spinal' potentials Cv7-Fz; their amplitudes are easily identifiable on the right, whereas on the left the N20 component is superimposed, c, CT shows a bilateral bleeding of the pontine tegmentum. From the CT the different SEP findings on both sides cannot be understood.
(figs 3, 4). Again, BAEP changes corresponded mostly to clinical changes, but there were exceptions, where the BAEP showed deterioration despite the clinical improvement of the patient (fig. 3). In other patients there was a gradual deterioration of the potentials
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m To.l6/*V
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I
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I
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I
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FIG. 4. Case 14, 41-yr-old female with left nuclear facial paresis, a Vk syndrome, right hemihypaesthesia and hemiataxia on admission, A, BAEP 10 days after the haemorrhage (upper traces) show an alteration after wave II on the left. On the right the short IPL III —V of 1.2 ms suggests an isolated loss of wave V. There is considerable improvement of the left BAEP about 1 month later {lower traces). SEPs (not shown here) were preserved after left median nerve stimulation and absent on the contralateral side. This patient made a good recovery, B, MRI showing haemorrhage into the left pontine tegmentum (left: lower pontine level; right: left parasagittal plane).
including wave I (fig. 5), thus preventing an assessment of brainstem functions. Two patients whose CT showed strong lateralization of the haemorrhage also had clearly different BAEP findings between sides. But there were also right-left differences of the BAEP in patients whose haemorrhage showed only slight or no lateralization on the CT. With regard to localization in the craniocaudal direction, it could not be predicted with any certainty whether the pathology of the potential would begin after
A. FERBERT AND OTHERS A BAEP
10 ms
«P'-
C47C3'-Fz
, ,v
- T 1.30/|V
1
5.1.
Oz-Fz
FIG. 5. Case 10, a 30-yr-old man in coma and tetraplegia on admission with slight improvement to coma vigil over the following days, A, BAEP showing only wave I bilaterally. Despite slight clinical improvement, wave I disappears in later recordings which may also be due to audiological factors. The patient died from cardiac arrest and was never 'brain dead' during the preceding course of his illness. Cortical SEPs (lowest pair of traces) were absent and VEPs (lowest panel) well preserved. B, CT showing massive pontine haemorrhage with extension to the midbrain and dilatation of the temporal horns of the lateral ventricles.
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SEP
Erb-cSh V-cSh
50 ms
FIG. 6. Case 3, left median nerve SEP in a patient with a large bilateral pontine haemorrhage. The N20 component of the SEP is absent bilaterally. The additional recordings of subcortical SEPs show preserved N13, N14 and P14 peaking at 13.2-13.4 ms. There are no major alterations of these subcortical SEP components which are consistent with their being generated below the pons. cSh = contralateral shoulder.
wave II or wave III from the CT. However, sagittal CT reconstruction or MRI were only available for a few patients. Somatosensory evoked potentials In 11 of the 17 patients cortical SEPs were absent bilaterally in the initial recording (fig. 5). In 8 of these patients the potential from the lower cervical spine (Cv7-Fz) was normal, in 2 patients it was moderately delayed due to a preexisting peripheral neuropathy, and in 1 patient it could not be assessed due to artefacts. Further montages to derive subcortical SEPs in some patients did not show a clear abnormality. In fig. 6 (lowest line) the P14 is not separate from P13. However, this pattern may also be observed in controls, and the finding can only be considered abnormal if earlier recordings show separation of these two waves. Unilateral preservation of the cortical SEPs was found in 3 patients and bilateral preservation in 3 patients. One of the latter patients re-bled, leading to bilateral loss
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of the SEP. In all except 2 patients, the amplitudes of cortical SEPs were reduced with regard to the amplitude ratio N13/N20. Central conduction time (CCT) was normal (fig. 3) in all cases in which it could be determined. All 11 patients with bilateral loss of cortical SEPs died after a period of between a few days and 3.5 months. Some of them regained some consciousness after the initial coma. They were tetraplegic with horizontal or total gaze paresis and had their eyes open, but with a delayed reaction to command, despite absent cortical SEPs. Such a finding with bilateral loss of cortical SEPs was never reversible, and not even transient. This was also true when the bleeding had resolved and only a small defect remained visible on the CT scan. On the other hand, of the 6 patients with unilateral or bilateral preserved SEPs, 3 made a fairly good recovery; 1 remained severely disabled at home; 2 patients died; 1 of them had bilaterally preserved SEPs prior to rebleeding which finally led to loss of SEPs. Unilateral preservation of the SEP could be found not only with unilateral haemorrhages (fig. 4) but also when the haemorrhage transgressed the midline of the pons (fig. 3). Electroencephalography EEG findings were available for 15 patients. There was no correlation either with the prognosis or with the clinical state. The findings displayed a (mostly slow) alpha rhythm in 10 patients, mixed alpha-theta activity in 3 and theta activity in 2, in most cases without desynchronization to visual stimuli. In some cases, serial recordings showed a progressive slowing of the activity. Visual evoked potentials In those 4 cases with VEP recordings, these were normal to flash stimulation. All patients had severe neurological deficits. This was also observed when the patients were tetraplegic and had only wave I preserved bilaterally in the BAEP (fig. 5). DISCUSSION
All our patients showed gross abnormalities in their BAEPs. This can well be explained by the location of the BAEP generators in the tegmentum of the upper medulla and the pons (Scherg and von Cramon, 1985). BAEPs are thus very sensitive for the detection of pontine bleeding. This sensitivity is even higher when compared with basilar artery thrombosis, where 18% of 56 investigated ears in 28 patients showed normal BAEPs (Ferbert et al., 1988). Basilar artery thrombosis may lead to infarction limited to the pontine base leaving the auditory pathways intact, whereas sparing of the tegmentum is very unusual in pontine haemorrhage and was not observed in our patients, nor in the 10 patients of Kushner and Bressman (1985) or the 24 cases with autopsy reported by Nakajima (1983). The specificity of the BAEP findings in pontine haemorrhage is low compared with CT or MRI. However, there are some differences between the BAEP findings in pontine
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haemorrhage and severe ischaemic vascular lesions of the brainstem. Loss of the whole potential, including wave I, was unusual on initial recordings in our patients with pontine haemorrhage whereas about one-quarter of the patients with basilar artery thrombosis had absent or only a flat desynchronized BAEP initially (Ferbert et al., 1988). There were no major age differences between these 2 patient groups which could explain a higher degree of cochlear dysfunction in the older age group. The direct ischaemic damage to the cochlea, which is often to be found in basilar artery thrombosis, is not observed after pontine haemorrhage, even if large, at least in initial recordings. Whether the progressive loss of all waves in the course of the disease, which was occasionally observed in our patients, is due to a compression of the arteries supplying the cochlea or whether this is due to ototoxic medication or other intensive care measures, remains undetermined. The prognostic value of the BAEP in our patients was not uniform. None of the patients with loss of all potentials after waves I and II bilaterally survived. When waves I—V were preserved with normal amplitudes, at least on one side, the prognosis was good. However, preservation of later waves with reduced amplitude could be found in patients with a poor as well as with a good prognosis. This is in contrast to experience with supratentorial lesions leading to secondary brainstem compression where a pathological BAEP reliably indicates a poor prognosis (Uziel et al., 1982; Cant et al., 1986; Riffel et al., 1987). Uncertainties in the prognosis of these patients only arise when BAEPs are normal, which may be associated with a good as well as a bad clinical course (Anderson et al., 1984; Cant et al., 1986). This difference may be explained by the following. A loss of BAEP waves in secondary brainstem compression is assumed to indicate not only the destruction of the auditory pathways, but more likely a lesion of the whole brainstem at the level of the generator of the altered wave, including brainstem structures lying rostral to this level. This explains the poor prognosis of these patients. In primary medullary and pontine lesions, however, loss of BAEPs may be due to a lesion which is relatively selective to the auditory pathways, leaving other brainstem structures at the same level or in the rostral direction intact. Two patients had only wave I of the BAEP preserved and both had preserved brainstem functions. This BAEP finding has been described as a typical finding in brain death (Starr, 1976; Mauguiere et al., 1982). Our results demonstrate that absence of all waves after I is not a reliable indicator of brain death in patients with pontine haemorrhage. The same has been demonstrated for severe ischaemic brainstem infarctions (Ferbert et al., 1988). The same probably holds true for patients with severe brainstem lesions of different aetiology and therefore the BAEP should not be used in the diagnosis of brain death in these patients. Delayed latency of peaks is assumed to be the main pathology of BAEP waves in demyelinating disease. In our patients reduction of amplitudes and loss of waves were the predominant findings. This has also been reported by Chiappa (1983) in a case with pontine haemorrhage. Most of our patients had large haemorrhages and it is not possible to draw any conclusions as to the generators of single BAEP waves in these patients. Only 1 patient had a small strictly unilateral pontine haematoma as described by Kase et al. (1980).
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This may be due to the fact that most of the recordings were carried out in the intensive care unit and thus patients with less severe syndromes may not have been included. The patient with unilateral bleeding into the pontine tegmentum displayed a severely altered BAEP on the ipsilateral side after wave II. This is in agreement with the conclusions of Chiappa (1983) in his short survey on lateralization of BAEP waves, who assumed that 'lesions . . . of the pons primarily produce BAEP abnormalities on the same side'. However, the pathological IV/V complex after contralateral ear stimulation in our patients suggests that these waves are generated for the most part in the contralateral ascending auditory pathways, which is substantiated by anatomical studies. Another patient with bleeding predominantly on the left had the most severe alterations of waves IV —V on the right. The intracranial recordings of Hashimoto et al. (1981) and Meller and Janetta (1982), as well as a report of a patient with a right tegmental pontine haemorrhage and isolated loss of wave V after contralateral ear stimulation (Hashimoto, 1986) support this interpretation. Thus a lesion of the tegmentum of the lateral pontomedullary junction will possibly lead to changes in the ipsilateral BAEP after wave II. Lesions which are more rostrally located in the middle or upper pons will disturb wave V (and possibly IV) after contralateral ear stimulation. As has been explained by Maurer et al. (1980) and Stockard et al. (1986), the search for generators of waves is limited by the fact that rarefaction and condensation clicks may provide different results from the same patient. This effect was also observed in our study. SEPs were of good prognostic value in our patients. Wherever 'cortical' SEPs (N20 and subsequent waves) were absent bilaterally, no patient recovered. Destruction of both medial lemnisci requires a large lesion. Only in the caudal pons are the medial lemnisci close to the midline, whereas they run more laterally in the middle and upper part of the pons (the term 'medial' can only be understood in relation to the location of the 'lateral' lemniscus). Thus a large lesion is required before SEPs disappear bilaterally. This explains the poor prognosis for our patients with loss of SEPs bilaterally and also why SEPs may be preserved on one side despite extension of the bleeding across the midline. The medial lemnisci must have been completely destroyed and not just compressed since the loss of SEPs was irreversible, even in patients who survived for many weeks and in whom the blood disappeared and only a minor lesion was visible on CT. The good prognostic value of SEP is also known from patients with head trauma (Anderson etal., 1984), hypoxic brain damage (Walser et al., 1985) and severe brainstem stroke (Ferbert et al., 1988). In one case only was bilateral absence of SEP associated with a good outcome in a patient with primary brainstem trauma (Rumpl et al., 1983). The fact that none of our 11 patients with bilateral loss of the N20 component of the SEP was brain dead underlines the fact that this finding is of no value for the diagnosis of brain death. In this respect our results are in clear contradiction to those of Belsh and Chokroverty (1987) who stated that 'absence of SEP after N13 and P13-P14 is characteristic of brain death'. Only changes including N13 are characteristic for brain death and this finding may develop in the further course (Buchner et al., 1988). The latter authors found some dissociation of the N13 component depending on the montage
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61
chosen. While N13 of a cephalic referenced lead (C2 —Fz) was reduced in amplitude shortly after brain death in some cases, the N13 peak was altered only later when using a C7 to 'jugulum' montage. N14 was always absent in brain death (Buchner etal., 1988). The neurological status of our patients with absent SEPs bilaterally was not uniform. Whereas all of them had severe tetraparesis or tetraplegia, some were in coma and others had their eyes open. The prognostic significance of unilateral loss of the median nerve SEP was ambiguous, but preserved cortical SEP may indicate a fairly good prognosis. 'Spinal' SEPs are most normal in patients with pontine haemorrhage apart from changes due to a peripheral neuropathy. Further montages of subcortical SEPs did not show a definite abnormality. Thus the recorded SEP must have been generated below the level of the pons (Buchner et al., 1987). Hemisphere functions may be nearly normal in patients with pontine bleeding. However, they can barely be assessed clinically because of the interruption of many efferent and afferent pathways. Intact function can only be demonstrated by the spontaneous EEG or by VEP recordings. The extreme form of this forebrain disconnection syndrome has been described as isolated brainstem death (Ferbert et al., 1986). The progressive slowing of the EEG activity detected in our patients cannot be explained by structural changes in the forebrain hemispheres. There was no correlation with hydrocephalus. It may be the result of reduced sensory input to the forebrain or progressive loss of arousal from the reticular formation. ACKNOWLEDGEMENTS We gratefully acknowledge the support of Professor W. Hacke. The Deutsche Forschungsgemeinschaft supported this work in part (Ha 1394/11). We also thank Mrs A. Behrendt and Mrs M. Dahmen for their excellent technical assistance and Mrs E Bonier and Mrs K. Seidel for secretarial work. REFERENCES ANDERSON DC, BUNDLIE S, ROCKSWOLD GL (1984) Multimodality evoked potentials in closed head trauma. Archives of Neurology, Chicago, 41, 369-374. BELSH JM, CHOKROVERTY S (1987) Short-latency somatosensory evoked potentials in brain-dead patients. Electroencephalography and Clinical Neurophysiology, 68, 75—78. BEWERMEYER H, NEVELING M, EBHARDT G, HEISS WD (1984) Spontane Ponsblutungen. Fortschritte der
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somesthe'siques precoces dans les comas neurologiques et la mort cerebrale. Revue d'Electroencephalographie et de Neurophysiologie, 12, 280—286. MAURER K, SCHAFER E, LEITNER H (1980) The effect of varying stimulus polarity (rarefaction vs. condensation) on early auditory evoked potentials (EAEPs). Electroencephalography and Clinical Neurophysiology, 50, 332 — 334. MBLLER AR, JANNETTA PJ (1982) Evoked potentials from the inferior colliculus in man. Electroencephalography and Clinical Neurophysiology, 53, 612—620. NAKAJIMA K (1983) Clinicopathological study of pontine hemorrhage. Stroke, 14, 485—493. O H SJ, KUBA T, SOYER A, CHOI IS, BONIKOWSKI FP, VITEK J (1981) Lateralization of brainstem lesions
by brainstem auditory evoked potentials. Neurology, New York, 3 1 , 14—18. PORTENOY RK, KURTZBERG D, AREZZO JC, SANDS GH, MILLER A, VAUGHAN HG (1985) Return to
alertness after brain-stem hemorrhage: a case with evoked potential and roentgenographic evidence of bilateral tegmental damage. Archives of Neurology, Chicago, 42, 85 — 88. RIFFEL B, STOHR M, TROST E, ULLRICH A, GRASER W (1987) Friihzeitige prognostische Aussage mittels
evozierter Potentiale beim schweren Schadel-Hirn-Trauma. EEG-EMG, 18, 192—199. RUMPL E, PRUGGER M, GERSTENBRAND F, HACKL JM, PALLUA A (1983) Central somatosensory conduction
time and short latency somatosensory evoked potentials in post-traumatic coma. Electroencephalography and Clinical Neurophysiology, 56, 583—596. SCHERG M, CRAMON D VON (1985) A new interpretation of the generators of BAEP waves I—V: results of a spatio-temporal dipole model. Electroencephalography and Clinical Neurophysiology, 62, 290-299. STARR A (1976) Auditory brain-stem responses in brain death. Brain, 99, 543—554. STOCKARD JJ, ROSSITER VS (1977) Clinical and pathologic correlates of brain stem auditory response abnormalities. Neurology, Minneapolis, 27, 316—325.
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STOCKARD JJ, STOCKARD JE, SHARBROUGH FW (1986) Brainstem auditory evoked potentials in neurology: methodology, interpretation, and clinical application. In: Electrodiagnosis in Clinical Neurology. Second edition. Edited by M. J. Aminoff. New York and Edinburgh: Churchill Livingstone, pp. 467-503. UZIEL A, BENEZECH J, LORENZO S, MONSTREY Y, DUBOIN MP, ROQUEFEUIL B (1982) Clinical applications
of brainstem auditory evoked potentials in comatose patients. Advances in Neurology, 32, 195—202. WALSER H, MATTLE H, KELLER HM, JANZER R (1985) Early cortical median nerve somatosensory evoked potentials: prognostic value in anoxic coma. Archives of Neurology, Chicago, 42, 32—38. WEISBERG LA (1986) Primary pontine haemorrhage: clinical and computed tomographic correlations. Journal of Neurology, Neurosurgery and Psychiatry, 49, 346 — 352. (Received January 3, J989. Revised February 20, 1989. Accepted March 7, 1989)
BRAINSTEM AUDITORY EVOKED POTENTIALS AND SOMATOSENSORY EVOKED POTENTIALS IN PONTINE HAEMORRHAGE CORRELATIONS WITH CLINICAL AND CT FINDINGS by A. FERBERT, H. BUCHNER and H. BRUCKMANN (From the Department of Neurology, Medical Faculty RWTH, Aachen, FRG) SUMMARY Electrophysiological studies were performed on 17 patients with pontine haemorrhage. Most had had massive hypertensive bleeding, leading to death in 12 of them within 3 months. Of the 5 surviving patients, 2 had a poor outcome and 3 a moderately good outcome. Brainstem auditory evoked potentials (BAEPs) and somatosensory evoked potentials (SEPs) were recorded in all patients, mostly with serial recordings. BAEPs were pathological in all patients. The most important finding was a reduction in amplitude or loss of waves. With a loss of waves after wave II bilaterally all patients died; the 2 patients with a normal amplitude of waves I —V at least on one side, survived in good condition. Further prognostic conclusions were not possible. The correlation with the clinical state was limited and was best for small unilateral tegmental haemorrhages. Eleven of the 17 patients suffered bilateral loss of the N20 component of the median nerve SEP. All these patients died. In patients with unilateral loss of the SEP the outcome could be favourable even if the bleeding extended across the midline. 'Subcortical' SEPs were not significantly altered. EEG findings in 15 and visual evoked potentials in 4 patients showed preserved forebrain electrical activity even in patients in poor condition.
INTRODUCTION
Pontine haemorrhage still has a poor prognosis (Goto et al., 1980; Bewermeyer et al., 1984) and therapeutic measures are limited. However, the wide use of CT has shown that in some patients with less severe brainstem syndromes a small pontine haemorrhage can be detected. Before the advent of CT these patients may have been suspected of suffering from ischaemic brainstem infarction. Thus a few patients may survive after a pontine haemorrhage (Kase et al., 1980; Nakajima, 1983; Howard, 1986; Weisberg, 1986). Vascular malformations such as angiomas are more likely to produce smaller haemorrhages, whereas large haemorrhages are usually due to severe longstanding hypertension. CT can easily detect a pontine haemorrhage. However, no precise prognostic factors are known to exist except for the fact that larger haemorrhages have a worse prognosis than smaller (Masiyama et al., 1985). Evoked potentials have proved to be of Correspondence to: Dr A. Ferbert, Department of Neurology, Medical Faculty RWTH, Pauwelsstrasse, D-5100 Aachen, FRG. © Oxford University Press 1990
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prognostic value in other brainstem lesions. However, surprisingly few results of brainstem auditory evoked potentials (BAEPs) and somatosensory evoked potentials (SEPs) in patients with pontine haemorrhage are reported in the literature apart from single case studies (Stockard and Rossiter, 1977; Oh et ai, 1981; Chiappa, 1983; Hammond et al., 1985; Portenoy etal., 1985; Hashimoto, 1986). There has as yet been no study using SEP or BAEP or both in pontine haemorrhage with a larger number of patients. The purpose of this study was to investigate whether BAEP and SEP have prognostic value in pontine haemorrhage, and to correlate evoked potential findings with clinical signs and the localization of the haemorrhage by imaging techniques. P A T I E N T S AND METHODS We investigated 17 patients with pontine haemorrhage. All patients underwent CT and 4 also had MRI. Patients with cerebellopontine haemorrhages, and with purely midbrain or medullary bleeding, were excluded, but in some patients with large haemorrhages there was some extension from the pons into the midbrain. No considerable extension of a pontine haemorrhage into the medulla was observed. The average age of our patients was 51 yrs, with a range of 2 5 - 7 3 yrs. There were 12 males and 5 females. Twelve patients had suffered from severe hypertension for many years, but in 2 others hypertension was only discovered after the bleeding. Five had a previous history of alcohol abuse. One patient was being treated with warfarin and another had several metastases from a malignant melanoma. Twelve patients died within 3 months of the haemorrhage. One had a prolonged survival but had a tetraplegia and respiratory problems which required assisted ventilation. He died after 4 months. Another was at home but severely disabled, confined to a wheelchair, and spending most of his time in bed. He died 1 yr after his haemorrhage. In 3 patients there was only a slight to moderate neurological deficit with spasticity in all four limbs and ocular motor abnormality after 6 months. All patients underwent BAEP and SEP investigations with serial recordings (an average of 3.5 per patient). In addition, the EEG was recorded in 15 patients and visual evoked potentials (VEPs) in 4 patients. Most of the patients were being treated in the intensive care unit. A neurological examination was performed before any electrophysiological studies. However, the neurological examination was sometimes limited by the fact that many patients were receiving sedative drugs because of assisted ventilation. When the signal/noise ratio was low, drugs blocking neuromuscular transmission were used in artificially ventilated and sedated patients. Thus nearly artefact-free records could be obtained for most patients. BAEPs were elicited by monaural stimulation of an alternating polarity with 90—95 dB HL. This high click intensity was chosen as older patients often have badly defined waves I using lower click intensities because of high-frequency hearing loss. The effect of selective click stimulation with either rarefaction or condensation was only studied in certain cases. Stimulus duration was 0.1 ms and frequency 14.1 Hz. The contralateral ear was masked with white noise of 70—75 dB HL. Platinum needle electrodes were placed over the mastoids and the vertex. Ipsilateral and contralateral recordings were carried out simultaneously. A total of 2000 sweeps was averaged with bandpass filters at 150 and 3000 Hz, 6 dB/octave. Latencies of waves I, III and V and the interpeak latencies I - V , I —III, III—V, HI—V were measured and compared with normative data from our institute ( ± 2 . 5 SD). The amplitude ratio V/I was calculated and considered to be pathological if the value was smaller than 1. Even if this ratio may occasionally be smaller than 1 in young healthy adults using high click intensities of 9 0 - 9 5 dB HL, it was always above 1 in our normal subjects older than 40 yrs; 16 of our 17 patients were in this age group. Amplitude of wave I is much more prone to age-dependent amplitude reduction than wave V. An amplitude ratio of less than 0.5 for waves III/I was defined as pathological. SEPs after electrical stimulation of the median nerve at the wrist were derived simultaneously from the contralateral hand field (C3/P3 or C4/P4 according to the 10/20 system) and the lower spine (Cv7-Fz).
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In some cases, further montages were studied (Erb's point; C2-Fz; Cz-contralateral shoulder; Cv7-'jugulum\ i.e., anterior neck just above the sternum). The bandpass was 5—1500 Hz; 50-500 sweeps were averaged depending on the signal/noise ratio. Latencies of N13 of the 'spinal' potential and N20 were measured, as well as central conduction time between both peaks. An amplitude ratio N20/N13 of less than 1 and differences in amplitudes between the right and left cortical potentials of more than 50% were considered to be abnormal. The amplitude of the N20 potential was measured from the peak of N20 to the peak of P25. In those cases in which the N20 component was reflected in the Cv7-Fz derivation, the amplitude of N13 was measured from the peak to baseline. The EEG was recorded according to the 10/20 system and VEPs from Oz to Fz using monocular or binocular flash stimulation with light-emitting diodes. RESULTS
Brainstem auditory evoked potentials BAEPs were pathological in all 17 patients with pontine haemorrhage (fig. 1). The predominant BAEP finding was a reduction in amplitude or loss of waves, whereas increased latencies with normal wave amplitude was less common. In initial recordings, normal waves I—III were found in 7 patients (8 ears). In most cases waves IV and V could not be distinguished from each other and were reduced in amplitude or occasionally delayed in latency. In some cases latencies of this wave complex were even shortened, so that the impression given was that of an isolated loss of wave V with preservation of wave IV {see fig. 4, right ear stimulation; an IPL III —V of 1.2 ms with a normal IPL I—III of 2.3 ms has never been observed in our control subjects). This interpretation was supported by the fact that both waves could not be seen separately on the contralateral recording. There was only one case with a very broad IV/V complex of high amplitude (fig. 1, Case 7) and another patient with delayed waves IV and V (fig. 1, Case 16). Normal waves I, and sometimes also waves II, with pathological waves III —V were found in 11 patients (17 ears). In most of these patients wave HI was reduced in amplitude and waves IV and V were absent or could scarcely be seen. In addition to the latter group there were 3 patients (5 ears) in whom only wave I was preserved, and no waves thereafter (fig. 1, Case 10). All 3 patients displayed spontaneous respiration and other preserved brainstem reflexes. In Case 9 only some small waves were derived between 4 and 8 ms which could not be classified. In another patient, no BAEP could be obtained on either side, even at the initial recording. This patient was known to have had hearing loss before the haemorrhage, although he was not completely deaf. In 8 patients the BAEPs were significantly different on the two sides whereas no differences or only minor changes were observed for the other 9. Differences in latency, amplitude or wave form could even be observed when comparing wave I on the two sides of 6 patients (fig. 1, Cases 1, 3, 5, 8, 11, 13). Major differences of BAEP after different click polarities could be demonstrated in one patient (fig. 2). Rarefaction clicks evoked waves I—IV bilaterally. Although condensation clicks evoked 4 waves on the right and only 3 waves on the left, the result of alternating click stimuli showed only waves I and II on the left and waves I—IV
52
A. FERBERT AND OTHERS BAEP
A/V~-^~c W A A ^ —
FIG. 1. BAEP findings for all 17 patients with ponti haemorrhage at the initial recording. There was preexisting hearing loss in Case 17 (lowest panel). Cases 4, 14 and 16 made a good recovery and Cases 7 and 15 remained severely disabled. All other patients died within 3 months.
17
10 ms
on the right. This effect was produced by considerable latency differences of waves II —IV to rarefaction-condensation stimulation on the right, whereas such latency differences were not present on the left. The CT scan in this case showed extensive
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FIG. 2. Case 2, 45-yr-old hypertensive patient with tetraplegia, ocular bobbing and 'coma vigil', A, BAEPS with alternating clicks in the lowest line show only waves I and II on the right. With rarefaction (RAR) and condensation (CON) clicks 4 waves can be seen. Different latencies of waves HI and IV (V) after rarefaction and condensation lead to cancellation of these waves in the alternating mode. On the left the difference between rarefaction and condensation is even more pronounced. The third panel down shows the addition of panels I and 2 by computer; there is no difference from alternating stimulation, B, CT scans showing the pontine haemorrhage which spares the medulla oblongata and the midbrain.
bilateral bleeding with a slight preponderance to the right, sparing the most caudal part of the pons (fig. 2). An exact correlation between BAEPs and neurological findings could not be detected. Severe BAEP abnormalities were found not only in tetraplegic patients but also in patients with only a moderate tetraparesis (fig. 3). They were found in patients who reacted to command (e.g., by ocular lid movements) and also in comatose patients. In the patient with the small haemorrhage in the left caudal pontine tegmentum, a left nuclear facial paresis, a one and a half syndrome and right hemihypaesthesia and hemiataxia correlated well with normal waves I and II and severely altered waves III—V to the left ear stimulation (fig. 4). The significance of the additional loss of wave V on the right will be discussed later. All patients who displayed loss of potentials after wave II bilaterally died. Both patients with normal amplitudes of waves I—V at least on one side survived. However, in the other BAEP pattern the prognostic value was somewhat vague: some patients died and others survived. Two different types of change could be observed in BAEP serial recordings. In some patients the BAEP indicated a change in brainstem function, leaving wave I unchanged
A. FERBERT AND OTHERS B Median
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/ C47C3'-Fz t
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I
I
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I
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FIG. 3. Case 4, 25-yr-old patient with left facial paresis, dissociated downbeat nystagmus, horizontal gaze paresis, anarthria, and right hemiparesis. A, BAEPS showing normal waves I bilaterally and a normal wave III on the right with severe alteration thereafter. The main pathology is a reduction in amplitude. In the further course of the patient, indicated by the recording dates, there is a deterioration of the left BAEP despite clinical recovery, B, cortical SEPs are normal after left median nerve stimulation and absent on the contralateral side. There is some reduction in amplitude of the left median nerve SEP in the further course of the patient. Normal 'spinal' potentials Cv7-Fz; their amplitudes are easily identifiable on the right, whereas on the left the N20 component is superimposed, c, CT shows a bilateral bleeding of the pontine tegmentum. From the CT the different SEP findings on both sides cannot be understood.
(figs 3, 4). Again, BAEP changes corresponded mostly to clinical changes, but there were exceptions, where the BAEP showed deterioration despite the clinical improvement of the patient (fig. 3). In other patients there was a gradual deterioration of the potentials
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m To.l6/*V
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I
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I
I
I
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I
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FIG. 4. Case 14, 41-yr-old female with left nuclear facial paresis, a Vk syndrome, right hemihypaesthesia and hemiataxia on admission, A, BAEP 10 days after the haemorrhage (upper traces) show an alteration after wave II on the left. On the right the short IPL III —V of 1.2 ms suggests an isolated loss of wave V. There is considerable improvement of the left BAEP about 1 month later {lower traces). SEPs (not shown here) were preserved after left median nerve stimulation and absent on the contralateral side. This patient made a good recovery, B, MRI showing haemorrhage into the left pontine tegmentum (left: lower pontine level; right: left parasagittal plane).
including wave I (fig. 5), thus preventing an assessment of brainstem functions. Two patients whose CT showed strong lateralization of the haemorrhage also had clearly different BAEP findings between sides. But there were also right-left differences of the BAEP in patients whose haemorrhage showed only slight or no lateralization on the CT. With regard to localization in the craniocaudal direction, it could not be predicted with any certainty whether the pathology of the potential would begin after
A. FERBERT AND OTHERS A BAEP
10 ms
«P'-
C47C3'-Fz
, ,v
- T 1.30/|V
1
5.1.
Oz-Fz
FIG. 5. Case 10, a 30-yr-old man in coma and tetraplegia on admission with slight improvement to coma vigil over the following days, A, BAEP showing only wave I bilaterally. Despite slight clinical improvement, wave I disappears in later recordings which may also be due to audiological factors. The patient died from cardiac arrest and was never 'brain dead' during the preceding course of his illness. Cortical SEPs (lowest pair of traces) were absent and VEPs (lowest panel) well preserved. B, CT showing massive pontine haemorrhage with extension to the midbrain and dilatation of the temporal horns of the lateral ventricles.
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SEP
Erb-cSh V-cSh
50 ms
FIG. 6. Case 3, left median nerve SEP in a patient with a large bilateral pontine haemorrhage. The N20 component of the SEP is absent bilaterally. The additional recordings of subcortical SEPs show preserved N13, N14 and P14 peaking at 13.2-13.4 ms. There are no major alterations of these subcortical SEP components which are consistent with their being generated below the pons. cSh = contralateral shoulder.
wave II or wave III from the CT. However, sagittal CT reconstruction or MRI were only available for a few patients. Somatosensory evoked potentials In 11 of the 17 patients cortical SEPs were absent bilaterally in the initial recording (fig. 5). In 8 of these patients the potential from the lower cervical spine (Cv7-Fz) was normal, in 2 patients it was moderately delayed due to a preexisting peripheral neuropathy, and in 1 patient it could not be assessed due to artefacts. Further montages to derive subcortical SEPs in some patients did not show a clear abnormality. In fig. 6 (lowest line) the P14 is not separate from P13. However, this pattern may also be observed in controls, and the finding can only be considered abnormal if earlier recordings show separation of these two waves. Unilateral preservation of the cortical SEPs was found in 3 patients and bilateral preservation in 3 patients. One of the latter patients re-bled, leading to bilateral loss
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of the SEP. In all except 2 patients, the amplitudes of cortical SEPs were reduced with regard to the amplitude ratio N13/N20. Central conduction time (CCT) was normal (fig. 3) in all cases in which it could be determined. All 11 patients with bilateral loss of cortical SEPs died after a period of between a few days and 3.5 months. Some of them regained some consciousness after the initial coma. They were tetraplegic with horizontal or total gaze paresis and had their eyes open, but with a delayed reaction to command, despite absent cortical SEPs. Such a finding with bilateral loss of cortical SEPs was never reversible, and not even transient. This was also true when the bleeding had resolved and only a small defect remained visible on the CT scan. On the other hand, of the 6 patients with unilateral or bilateral preserved SEPs, 3 made a fairly good recovery; 1 remained severely disabled at home; 2 patients died; 1 of them had bilaterally preserved SEPs prior to rebleeding which finally led to loss of SEPs. Unilateral preservation of the SEP could be found not only with unilateral haemorrhages (fig. 4) but also when the haemorrhage transgressed the midline of the pons (fig. 3). Electroencephalography EEG findings were available for 15 patients. There was no correlation either with the prognosis or with the clinical state. The findings displayed a (mostly slow) alpha rhythm in 10 patients, mixed alpha-theta activity in 3 and theta activity in 2, in most cases without desynchronization to visual stimuli. In some cases, serial recordings showed a progressive slowing of the activity. Visual evoked potentials In those 4 cases with VEP recordings, these were normal to flash stimulation. All patients had severe neurological deficits. This was also observed when the patients were tetraplegic and had only wave I preserved bilaterally in the BAEP (fig. 5). DISCUSSION
All our patients showed gross abnormalities in their BAEPs. This can well be explained by the location of the BAEP generators in the tegmentum of the upper medulla and the pons (Scherg and von Cramon, 1985). BAEPs are thus very sensitive for the detection of pontine bleeding. This sensitivity is even higher when compared with basilar artery thrombosis, where 18% of 56 investigated ears in 28 patients showed normal BAEPs (Ferbert et al., 1988). Basilar artery thrombosis may lead to infarction limited to the pontine base leaving the auditory pathways intact, whereas sparing of the tegmentum is very unusual in pontine haemorrhage and was not observed in our patients, nor in the 10 patients of Kushner and Bressman (1985) or the 24 cases with autopsy reported by Nakajima (1983). The specificity of the BAEP findings in pontine haemorrhage is low compared with CT or MRI. However, there are some differences between the BAEP findings in pontine
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haemorrhage and severe ischaemic vascular lesions of the brainstem. Loss of the whole potential, including wave I, was unusual on initial recordings in our patients with pontine haemorrhage whereas about one-quarter of the patients with basilar artery thrombosis had absent or only a flat desynchronized BAEP initially (Ferbert et al., 1988). There were no major age differences between these 2 patient groups which could explain a higher degree of cochlear dysfunction in the older age group. The direct ischaemic damage to the cochlea, which is often to be found in basilar artery thrombosis, is not observed after pontine haemorrhage, even if large, at least in initial recordings. Whether the progressive loss of all waves in the course of the disease, which was occasionally observed in our patients, is due to a compression of the arteries supplying the cochlea or whether this is due to ototoxic medication or other intensive care measures, remains undetermined. The prognostic value of the BAEP in our patients was not uniform. None of the patients with loss of all potentials after waves I and II bilaterally survived. When waves I—V were preserved with normal amplitudes, at least on one side, the prognosis was good. However, preservation of later waves with reduced amplitude could be found in patients with a poor as well as with a good prognosis. This is in contrast to experience with supratentorial lesions leading to secondary brainstem compression where a pathological BAEP reliably indicates a poor prognosis (Uziel et al., 1982; Cant et al., 1986; Riffel et al., 1987). Uncertainties in the prognosis of these patients only arise when BAEPs are normal, which may be associated with a good as well as a bad clinical course (Anderson et al., 1984; Cant et al., 1986). This difference may be explained by the following. A loss of BAEP waves in secondary brainstem compression is assumed to indicate not only the destruction of the auditory pathways, but more likely a lesion of the whole brainstem at the level of the generator of the altered wave, including brainstem structures lying rostral to this level. This explains the poor prognosis of these patients. In primary medullary and pontine lesions, however, loss of BAEPs may be due to a lesion which is relatively selective to the auditory pathways, leaving other brainstem structures at the same level or in the rostral direction intact. Two patients had only wave I of the BAEP preserved and both had preserved brainstem functions. This BAEP finding has been described as a typical finding in brain death (Starr, 1976; Mauguiere et al., 1982). Our results demonstrate that absence of all waves after I is not a reliable indicator of brain death in patients with pontine haemorrhage. The same has been demonstrated for severe ischaemic brainstem infarctions (Ferbert et al., 1988). The same probably holds true for patients with severe brainstem lesions of different aetiology and therefore the BAEP should not be used in the diagnosis of brain death in these patients. Delayed latency of peaks is assumed to be the main pathology of BAEP waves in demyelinating disease. In our patients reduction of amplitudes and loss of waves were the predominant findings. This has also been reported by Chiappa (1983) in a case with pontine haemorrhage. Most of our patients had large haemorrhages and it is not possible to draw any conclusions as to the generators of single BAEP waves in these patients. Only 1 patient had a small strictly unilateral pontine haematoma as described by Kase et al. (1980).
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This may be due to the fact that most of the recordings were carried out in the intensive care unit and thus patients with less severe syndromes may not have been included. The patient with unilateral bleeding into the pontine tegmentum displayed a severely altered BAEP on the ipsilateral side after wave II. This is in agreement with the conclusions of Chiappa (1983) in his short survey on lateralization of BAEP waves, who assumed that 'lesions . . . of the pons primarily produce BAEP abnormalities on the same side'. However, the pathological IV/V complex after contralateral ear stimulation in our patients suggests that these waves are generated for the most part in the contralateral ascending auditory pathways, which is substantiated by anatomical studies. Another patient with bleeding predominantly on the left had the most severe alterations of waves IV —V on the right. The intracranial recordings of Hashimoto et al. (1981) and Meller and Janetta (1982), as well as a report of a patient with a right tegmental pontine haemorrhage and isolated loss of wave V after contralateral ear stimulation (Hashimoto, 1986) support this interpretation. Thus a lesion of the tegmentum of the lateral pontomedullary junction will possibly lead to changes in the ipsilateral BAEP after wave II. Lesions which are more rostrally located in the middle or upper pons will disturb wave V (and possibly IV) after contralateral ear stimulation. As has been explained by Maurer et al. (1980) and Stockard et al. (1986), the search for generators of waves is limited by the fact that rarefaction and condensation clicks may provide different results from the same patient. This effect was also observed in our study. SEPs were of good prognostic value in our patients. Wherever 'cortical' SEPs (N20 and subsequent waves) were absent bilaterally, no patient recovered. Destruction of both medial lemnisci requires a large lesion. Only in the caudal pons are the medial lemnisci close to the midline, whereas they run more laterally in the middle and upper part of the pons (the term 'medial' can only be understood in relation to the location of the 'lateral' lemniscus). Thus a large lesion is required before SEPs disappear bilaterally. This explains the poor prognosis for our patients with loss of SEPs bilaterally and also why SEPs may be preserved on one side despite extension of the bleeding across the midline. The medial lemnisci must have been completely destroyed and not just compressed since the loss of SEPs was irreversible, even in patients who survived for many weeks and in whom the blood disappeared and only a minor lesion was visible on CT. The good prognostic value of SEP is also known from patients with head trauma (Anderson etal., 1984), hypoxic brain damage (Walser et al., 1985) and severe brainstem stroke (Ferbert et al., 1988). In one case only was bilateral absence of SEP associated with a good outcome in a patient with primary brainstem trauma (Rumpl et al., 1983). The fact that none of our 11 patients with bilateral loss of the N20 component of the SEP was brain dead underlines the fact that this finding is of no value for the diagnosis of brain death. In this respect our results are in clear contradiction to those of Belsh and Chokroverty (1987) who stated that 'absence of SEP after N13 and P13-P14 is characteristic of brain death'. Only changes including N13 are characteristic for brain death and this finding may develop in the further course (Buchner et al., 1988). The latter authors found some dissociation of the N13 component depending on the montage
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chosen. While N13 of a cephalic referenced lead (C2 —Fz) was reduced in amplitude shortly after brain death in some cases, the N13 peak was altered only later when using a C7 to 'jugulum' montage. N14 was always absent in brain death (Buchner etal., 1988). The neurological status of our patients with absent SEPs bilaterally was not uniform. Whereas all of them had severe tetraparesis or tetraplegia, some were in coma and others had their eyes open. The prognostic significance of unilateral loss of the median nerve SEP was ambiguous, but preserved cortical SEP may indicate a fairly good prognosis. 'Spinal' SEPs are most normal in patients with pontine haemorrhage apart from changes due to a peripheral neuropathy. Further montages of subcortical SEPs did not show a definite abnormality. Thus the recorded SEP must have been generated below the level of the pons (Buchner et al., 1987). Hemisphere functions may be nearly normal in patients with pontine bleeding. However, they can barely be assessed clinically because of the interruption of many efferent and afferent pathways. Intact function can only be demonstrated by the spontaneous EEG or by VEP recordings. The extreme form of this forebrain disconnection syndrome has been described as isolated brainstem death (Ferbert et al., 1986). The progressive slowing of the EEG activity detected in our patients cannot be explained by structural changes in the forebrain hemispheres. There was no correlation with hydrocephalus. It may be the result of reduced sensory input to the forebrain or progressive loss of arousal from the reticular formation. ACKNOWLEDGEMENTS We gratefully acknowledge the support of Professor W. Hacke. The Deutsche Forschungsgemeinschaft supported this work in part (Ha 1394/11). We also thank Mrs A. Behrendt and Mrs M. Dahmen for their excellent technical assistance and Mrs E Bonier and Mrs K. Seidel for secretarial work. REFERENCES ANDERSON DC, BUNDLIE S, ROCKSWOLD GL (1984) Multimodality evoked potentials in closed head trauma. Archives of Neurology, Chicago, 41, 369-374. BELSH JM, CHOKROVERTY S (1987) Short-latency somatosensory evoked potentials in brain-dead patients. Electroencephalography and Clinical Neurophysiology, 68, 75—78. BEWERMEYER H, NEVELING M, EBHARDT G, HEISS WD (1984) Spontane Ponsblutungen. Fortschritte der
Neurologie-Psychiatrie, 52, 259-276. BUCHNER H, FERBERT A, BRUCKMANN H, HACKE W (1987) The subcortical generated somatosensory
evoked potentials in non-cephalic, cephalic, and anterior neck referenced recordings in a patient with a cervico-medullary lesion: a clue to the identification of the P14/N14 and N13 generators. Journal of Neurology, 234, 412-415. BUCHNER H, FERBERT A, HACKE W (1988) Serial recording of median nerve stimulated subcortical somatosensory evoked potentials (SEPs) in developing brain death. Electroencephalography and Clinical Neurophysiology, 69, 14 — 23. CANT BR, HUME AL, JUDSON JA, SHAW NA (1986) The assessment of severe head injury by short-latency somatosensory and brain-stem auditory evoked potentials. Electroencephalography and Clinical Neurophysiology, 65, 188-195.
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