Role of short latency evoked potentials in the diagnosis of brain death.

OBJECTIVE: The aim of this study is to confirm the effectiveness of auditory brain-stem responses (ABRs) and somatosensory evoked potentials (SEPs) in the diagnosis of brain death (BD). METHODS: ABRs and SEPs were recorded at the same session in 130 BD patients (age range 8-77 years, 81 male and 49 female). Twenty-four cases were submitted to serial recordings from preterminal conditions through BD. RESULTS: ABRs were absent in 92 cases (70.8%), only waves I or I-II were present in 32 cases (24.6%), while in the remaining 6 patients (4.6%) waves V and/or III were still present, excluding the death of the brain-stem. In 4 cases (3.1%) SEPs showed the absence of all components following the cervical N9, preventing the diagnosis of BD. Among 126 cases (96.9%) with preserved cervical N9-N13 SEPs confirmed the absence of brain-stem activity in 122 cases (93.7%), in whom no waves following P11 or P13 were recordable. SEPs excluded the diagnosis of BD in the remaining 4 cases (3.2%) showing preserved P14 and/or N18. In all pre terminal patients the far-field P14-N18 were present, and their disappearance was closely related to the onset of BD. CONCLUSIONS: The combined us of ABRs and SEPs was able to confirm BD in almost all patients, providing an objective confirmation of the diagnosis, and to exclude it in 7 cases, thus improving the reliability of diagnosis.     

SEP testing in deeply comatose and brain dead patients: the role of nasopharyngeal, scalp and earlobe derivations in recording the P14 potential.

Median nerve somatosensory evoked potentials (SEPs) were tested in 50 patients (20 brain dead, 18 comatose and in 12 progressing from coma to brain death, i.e., 32 cases with brain death and 30 cases with coma were recorded). Derivations were taken from nasopharynx, earlobes, scalp, and neck using cephalic and non-cephalic references. Cortical and subcortical SEP components were evaluated, focussing on the P14 potential. There is evidence that rostral and caudal parts of the P14 generator (lemniscus medialis) are differently affected in brain death, resulting in an abolition of the rostral part, while occasionally leaving intact for some time the caudal part. Non-cephalic referenced scalp records pick up the whole P14 dipole, whereas nasopharyngeal and earlobe derivations pick up different parts of P14, depending on the reference used. Scalp-to-nasopharynx records derive the most rostral part of P14; this "rostral P14" was bilaterally lost in all brain dead patients, but preserved in all deeply comatose patients with diffuse brain-stem injuries. Scalp-to-earlobe records, in contrast, picked up a P14 dipole segment reaching more caudally, resulting in a P14 potential also in brain dead patients. It is concluded that midfrontal scalp-to-nasopharynx derivations give the most valuable contribution to the electrophysiological assessment of brain death versus deep coma.     

Short-latency somatosensory evoked potentials and magnetic resonance imaging in the medial medullary syndrome

A 57-year-old woman was admitted to Kakeyu Hospital complaining of paresis of the left upper and lower extremities which suddenly developed three years ago. Neurological examination revealed spastic paresis of the left upper and lower limbs without facial and lingual paresis. The reflexes were abnormally brisk on both sides but they were more remarkable on the left side, which also showed Babinski's sign. Sensitivity to light touch and vibration was moderately decreased and sensitivity to pinprick and joint position was minimally decreased in the left upper and lower extremities. No cerebellar sign was observed. Needle EMG disclosed large motor units with an amplitude of 4-5 mV and a duration of 8 msec in the light half of the tongue during weak contraction. MRI using a 0.5-T superconducting magnetic resonance unit detected a small, wedge-shaped infarction in the anterior medial portion of the medulla just below the pontomedullary junction. Somatosensory evoked potentials (SEPs) after median nerve stimulation with a non-cephalic reference were recorded. After stimulation of the left side, the scalp-recorded P13 was recognized at the normal latency, but the later components, N16 and N18, were apparently absent. On the other hand, SEPs in another case with thalamic hemorrhage revealed normal N16 potential with absence of N18 on the affected side. From these SEP findings and the reports on SEPs in lesions of the brain stem or thalamus, it was suggested that P13 is abnormal in lower medullary lesions and is preserved in upper medullary lesions, and that N16 is abnormal in brain stem lesions and is preserved or changed a little in thalamic lesions.     

Pyramidal tract function during onset of brain death.

In 51 patients with primary brain lesions, who fulfilled the criteria of brain death, sequential recording of transcranial magnetic evoked potentials (TMEPs) and somatosensory evoked potentials (SEPs) were performed. In all comatose patients with apnoeic cranial nerve areflexia the TMEP could not be elicited, while the response after cervical magnetic stimulation was always preserved. Similarly, no cortical SEPs were preserved in apnoeic cranial nerve areflexia; however, the cervical somatosensory response was preserved in 44%. In deteriorating patients with coma grade III TMEPs were preserved in 3 instances, while cortical SEPs were already absent. Current brain death criteria, however, were not challenged, as TMEPs were absent in all 51 patients, at the latest when apnoea was noted.     

The prognostic value of evoked responses from primary somatosensory and auditory cortex in comatose patients.

OBJECTIVE: To evaluate somatosensory and auditory primary cortices using somatosensory evoked potentials (SEPs) and middle latency auditory evoked potentials (MLAEPs) in the prognosis of return to consciousness in comatose patients. METHODS: SEPs and MLAEPs were recorded in 131 severe comatose patients. Latencies and amplitudes were measured. Coma had been caused by transient cardiac arrest (n=49), traumatic brain injury (n=22), stroke (n=45), complications of neurosurgery (n=12) and encephalitis (n=3). One month after the onset of coma patients were classified as awake, still comatose or dead. Three months after (M3), they were classified into one of the 5 categories of the Glasgow outcome scale (GOS). RESULTS: At M3, 41.2% were dead, 47.3% were conscious (GOS 3-5) and 11.5% had not recovered consciousness. None of the patients in whom somatosensory N20 and auditory Pa were absent did return to consciousness and in the post-anoxic group, reduced cortical amplitude too was always associated with bad outcome. Conversely, N20 and Pa were present, respectively, in 33/69 and 34/69 patients who did not recover. CONCLUSIONS: The prognostic value of SEPs and MLAEPs in comatose patients depends on the cause of coma. Measurement of response amplitudes is informative. Abolition of cortical SEPs and/or cortical MLAEPs precludes post-anoxic comatose patients from returning to consciousness (100% specificity). In any case, the presence of short latency cortical somatosensory or auditory components is not a guarantee for return to consciousness. Late components should then be recorded.     

Changes in short latency SEPs (S-SEPs) to median nerve stimulation in brain dead patients

Short latency SEPs (S-SEPs) to median nerve stimulation consist of positive waves of P1, P2, P3 and P4, followed by negative waves of N 16 and N 19. These potential reflect activities of peripheral nerve, dorsal column of the cervical cord and medial lemniscus. The origins of these waves are considered as follows, P1--peripheral part of the brachial plexus, P2--the entry into the spinal cord or the dorsal column, P3--dorsal column nucleus or upper cervical cord, P4--the medial lemniscus, N 16--rostral brain stem or the thalamus, and N 19--thalamocortical projection or the cortex. The purpose of the present study is to elucidate changes of S-SEPs in brain dead patients. Fifteen brain dead patients were examined with S-SEPs. In addition to that, thirteen cases with lesions of subcortical or the brain stem but not in the state of brain death were studied for the controls. S-SEPs with non-cephalic references, conventional SEPs with earlobe reference and the evoked potentials at the Erb's point were recorded in all these cases. Serial recordings were performed in six brain dead cases during the process of rostro-caudal deterioration of the brain stem functions due to cerebral herniation. In the state of brain death, only P1 and P2 were recorded in eleven cases, and in three cases, only P1 was recorded. The other case with anoxic brain damage showed flat S-SEPs and the evoked potentials at the Erb's point could merely be obtained by the supramaximal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evoked potentials in basilar artery thrombosis: correlation with clinical and angiographic findings

In 28 patients with vertebro-basilar or basilar artery thrombosis brain-stem auditory evoked potentials (BAEPs) and somatosensory evoked potentials (SEPs) have been recorded. Visual evoked potentials (VEPs) were recorded in 7 of these 28 patients. In 24 patients the diagnosis was angiographically proven and in 4 patients Doppler sonography and computerized tomography suggested this diagnosis. The BAEP and SEP findings were correlated to clinical and angiographical signs. BAEPs could be classified into 6 different patterns. In more than half of the patients different BAEP patterns from the two ears could be found. A pathological IV/V complex was most often found in comatose patients and in patients with a basilar artery occlusion distal to the anterior inferior cerebellar artery. Prolonged interpeak latency of I-III was mainly found in alert or drowsy patients with caudal occlusions. The frequent occurrence of a BAEP with only wave I preserved, or with no waves preserved, in patients with brain-stem functions suggests that BAEPs are not useful in the diagnosis of brain death when basilar artery thrombosis is suspected. SEPs were either absent bilaterally or else severely altered on one side in all comatose patients. In alert patients, including those with 'locked-in' syndrome, SEPs were never absent bilaterally. Increased N13-N20 interpeak latency was an uncommon finding in this series. There was no correlation between the SEP and the angiographically proven location of the occlusion. In the 'locked-in' syndrome both SEP and BAEP findings were non-uniform. Normal SEPs were sometimes found in combination with severely altered BAEPs, suggesting partial deafferentation. Since basilar artery thrombosis is now a treatable condition, early diagnosis and documentation of functional deficits moves into a more important clinical area than heretofore.     

Origin of N18 and P14 far-fields of median nerve somatosensory evoked potentials studied in patients with a brain-stem lesion

Somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded in 3 patients with a brain-stem or medullary lesion documented by clinical and CT or MRI evidence. The positive P14 and negative N18 scalp far-fields were preserved. The results suggest that P14 reflects the spike volley in caudal medial lemniscus, and that the N18 neural generators are located in the medulla, probably in the dorsal column nuclei and/or the accessory inferior olives.     

Nasopharyngeal recordings of somatosensory evoked potentials document the medullary origin of the N18 far-field.

Because the nasopharyngeal electrode provides non-invasive access to the ventral brain-stem at the medullo-pontine level we used it for recording somatosensory evoked potentials (SEPs) to median nerve stimulation (non-cephalic reference). After the P9 and P11 far-fields, the nasopharyngeal SEPs disclosed a negative-going component which was interpreted as the near-field equivalent of the P14 scalp far-field generated in the caudal part of the medial lemniscus. Nasopharyngeal SEPs also revealed a large N18 with voltage and features strikingly similar to those of the scalp-recorded N18 far-field. These results suggest that N18 is generated in the medulla and not more rostrally in the brain-stem. The use of a nasopharyngeal electrode as reference for topographic brain mapping is discussed. The paper documents the feasibility and relevance of nasopharyngeal recordings for non-invasive analysis of short-latency SEPs.     

Somatosensory evoked potentials (SEPs) recorded from deep brain stimulation (DBS) electrodes in the thalamus and subthalamic nucleus (STN).

OBJECTIVE: To examine the location of deep brain stimulation (DBS) electrode somatosensory evoked potentials (SEPs) and determine the generators of the median nerve SEPs recorded in thalamus and subthalamic nucleus (STN). METHODS: SEPs were recorded from contacts of DBS electrodes and microelectrodes in thalamus and STN to establish the latencies of N13, N18 and N20 in 24 patients (8 tremor, 4 chronic pain, 12 Parkinson disease) undergoing chronic DBS. RESULTS: A large SEP with a mean latency of 17.9+/-1.7 ms was recorded from thalamic contacts. Phase reversal occurred at the horizontal level of the anterior commissure-posterior commissure line. Smaller potentials with similar latency but no reversal could be recorded from STN electrodes. CONCLUSIONS: We propose that the thalamic SEP is generated by excitatory post-synaptic potentials in sensory relay neurons in nucleus ventrocaudalis. A small potential in STN at a similar latency, may be due to volume conduction from thalamus. Intraoperative and postoperative SEP recordings from DBS electrodes could be used to determine the optimal position of the contacts relative to the sensory pathways and the choice of contacts for chronic stimulation.     

Distribution of brainstem somatosensory evoked potentials following upper and lower limb stimulation.

OBJECTIVE: Because somatosensory evoked potentials (SEP) to lower limb stimulation have not been recorded from the brainstem to the extent that upper limb SEPs have been studied, we compared brainstem recordings in response to both median nerve (MN) and posterior tibial nerve (PTN)stimulation. METHODS: SEPs were recorded directly from the dorsal surface of the brainstem in four patients with fourth ventricle tumors. RESULTS: Following MN stimulation, medullary SEPs were characterized by a major negativity (N1) preceded by a small positivity (P1) and followed by a large positivity (P2). In the pons, triphasic waves with predominant negativity were obtained. With PTN stimulation, similar medullary SEPs with a P1'-N1'-P2' configuration and pontine SEPs with a triphasic waveform were obtained. CONCLUSIONS: Since the distribution of PTN SEP was identical to that of MN SEP, PTN SEPs are thought to be generated by mechanisms similar to those for MN SEP. Thus, the P1' and N1' of medullary SEP would be generated by the dorsal column fibers that terminate in the nucleus, with P2' possibly arising postsynaptically in the nucleus. The triphasic PTN SEP from the pons reflects an axonal potential generated in the medial lemniscal pathway.     

Somatosensory evoked potentials and auditory brain-stem responses in congenital hypothyroidism. I. A longitudinal study before and after treatment in six infants detected in the neonatal period

We report the results of a longitudinal study of auditory brain-stem responses (ABRs) and somatosensory evoked potentials (SEPs) performed in 6 children with congenital hypothyroidism. These infants were detected by the Quebec Network for Genetic Medicine and treated early. ABRs and SEPs were recorded both before and 2 weeks after the initiation of therapy and at 6 months of age. Before treatment, for SEP, we found increased wave N19, P22 latencies and N13-N19, N19-P22 interpeak latencies (IPLs) in congenital hypothyroid (CH) children. For ABR, there were increased wave I latencies with normal I-V IPLs. Substitutive therapy improved these abnormalities although this improvement was more evident after a shorter period of time for ABRs than for SEPs. Even at 6 months, 2 CH children still showed increased N13-N19 IPLs. Both had very low serum T4 levels at the time of diagnosis and one had also a very small knee surface area, both criteria indicating a severe hypothyroidism. It will be interesting to verify if initial and persisting increase of N13-N19 IPL is associated with later neuropsychological problems.     

Short latency evoked potentials: new criteria for brain death?

The aim of this study was to evaluate whether the auditory brain stem responses (ABR) and short latency somatosensory potentials (SEP) from median nerve stimulation are effective tools in the confirmation of brain death. Thirty six brain dead patients were submitted to ABR and 24 to SEP in the same session. All waves of the ABR were absent in 28 (77.8 per cent) patients, while only wave I was present in the others (22.2 per cent). In SEP recordings the components later than P13 were absent in 17 (70.8 per cent) of cases; in the remaining seven patients (29.2 per cent) a N13/P13 dissociation (namely, retention of the cervical N13 and absence of the far-field P13) was found. The results suggest that SEP and ABR are reliable tools in the diagnosis of brain death and should be included in the criteria: they enable the functional status of two pathways in the brainstem to be checked, which cannot be explored by the clinical examination.     

Pitfalls in diagnosing brain death in infancy

A 3-year-old child with phenotypic trisomy 18 syndrome survived 26 days after a cardiopulmonary arrest, secondary to an acute viral illness. The child was deeply comatose. No barbiturates, other sedatives, or aminoglycoside antibiotics had been recently administered. The child was normothermic with adequate cardiovascular function. Brain stem function was absent, as assessed by testing of brain stem reflexes. Serial cerebral radionuclide angiograms (CRAG) documented intact cerebral blood flow while electrocerebral silence (ECS) was present on two consecutive EEG recordings within 24 hours. Preservation of intracranial circulation was confirmed by rapid rotational computed tomographic (CT) scans. Cranial CT scans also revealed communicating hydrocephalus, and bilateral basal ganglia hemorrhages. This unusual case illustrates discordance between apparent irreversible loss of cortical function as indicated by electrocerebral silence with preserved cerebral blood flow. The implications of these apparent paradoxical events will be discussed in the context of defining brain death in children.     

Neural generators of N18 and P14 far-field somatosensory evoked potentials studied in patients with lesion of thalamus or thalamo-cortical radiations

Somatosensory evoked potentials (SEPs) to electrical stimulation of the right or left median nerve were studied in 4 patients with hemianesthesia and a severe thalamic or suprathalamic vascular lesion on one side. The SEPs were recorded with a non-cephalic reference. The normal side of each patient served as his or her own control. The lesion consistently abolished the parietal N20-P27-P45 and the prerolandic P22-N30 SEP components. It did not significantly affect the P9-P11-P14 positive far fields, nor the widespread bilateral N18 SEP component. This allowed N18 features to be studied without interference from cortical components. It is proposed that N18 reflects several deeply located generators in brain stem and/or thalamus whereas N20 represents the earliest cortical response of the contralateral post-central receiving areas.     

Serial recording of median nerve stimulated subcortical somatosensory evoked potentials (SEPs) in developing brain death

Subcortical somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded serially in 35 patients during the evolution towards brain death and in brain death. Neuropathological alterations of the central nervous system down to the C1/C2 spinal cord segment in brain death are well known. SEP components supposed to be generated above this level should be lost in brain death, while components generated below should not be altered. Erb's point, scalp and neck potentials were recorded at C3/4, or over the spinous process C7, using an Fz reference. In 10 patients additional montages, including spinous process C2-Fz, a non-cephalic reference (Fz-contralateral shoulder) and a posterior to anterior neck montage (spinous process C7-jugulum) were used. The cephalic referenced N9 and N11 peaks remained unchanged until brain death. N9 and N11 decreased in parallel in amplitude and increased in latency after systemic effects like hypoxia or hypothermia occurred. The cephalic referenced 'N14' decreased in amplitude and increased in latency after the clinical brain death syndrome was observed, while N13 in the posterior to anterior neck montage remained unchanged. The alteration of 'N14' went parallel to the decrease of the P14 amplitude. The subcortical SEPs in the cephalic referenced lead are supposed to be a peak composed by a horizontally orientated dorsal horn generated N13 and a rostrally orientated P14 arising at the level of the foramen magnum. The deterioration of the non-cephalic referenced P14 and of its cephalic referenced reflection 'N14' seems to provide an additional objective criterion for the diagnosis of brain death.     

Thoracic outlet syndrome. Electrophysiologic reappraisal

Eighteen patients with thoracic outlet syndrome (TOS) were examined with somatosensory evoked potentials (SEPs). All the patients had normal median N9 (brachial plexus) amplitudes, whereas 12 had low-amplitude ulnar N9 potentials. The conduction in the ulnar nerve from N9 to N13 (brachial plexus to cord) was prolonged in seven of 18 patients. The combination of the ulnar N9 amplitude, the ulnar N9 to N13 conduction, and routine ulnar F-wave determination yielded positive quantitative diagnostic information in 17 of 18 cases. The SEPs appear to be a reliable, sensitive, quantitative, and non-invasive diagnostic tool in examining patients with TOS.     

Sensorimotor central conduction time in comatose patients.

Motor evoked potentials (MEPs) following magnetic stimulation were recorded in 22 patients comatose as a result of head injury (13 cases), stroke (7 cases) or anoxia (2 cases). Somatosensory evoked potentials (SEPs) from median nerve were recorded as well in 19 cases in the same session. Thirteen patients died or remained vegetative (59.1%), 3 were severely disabled (13.6%) and 6 showed a good recovery (27.3%). MEPs were significantly related to the outcome; they appeared to be a more accurate prognostic indicator than the Glasgow Coma Scale (GCS). However, 1 out of 6 patients with bilaterally absent MEPs (16.7%) showed a good recovery. SEPs were significantly related to the outcome as well, but the combined use of SEP and MEP improved the outcome prediction, decreasing the rate of false negatives. Two patients had normal sensorimotor function, 13 a combined sensorimotor dysfunction, while 4 had a pure motor dysfunction. Our results suggest that SEPs and MEPs may improve the assessment of sensorimotor dysfunction in comatose patients. A significant relationship between MEPs and outcome appears to exist, but the assessment of MEP reliability requires further study.     

Segmental dysfunction of the cervical cord revealed by abnormalities of the spinal N13 potential in cervical spondylotic myelopathy.

We studied somatosensory potentials (SEPs) evoked by stimulation of radial, median, and ulnar nerves in 11 patients with MRI evidence of cervical spondylosis. All patients presented with progressive spastic paraparesis that was either isolated or associated with lower motor neuron signs in the upper limbs, with preserved joint, touch, pain, and temperature sensations in the four limbs. In all patients, scalp SEPs reflecting the activity of the dorsal column system up to the parietal cortex were normal while segmental cervical cord dysfunction was manifested by an abnormal spinal N13 potential in 95% of radial, 90% of median, and 54% of ulnar nerve SEPs. These subclinical abnormalities of the spinal N13 SEP probably result from reduced blood supply due to compression of the anterior spinal artery in patients with cervical spondylotic myelopathy.     

Preserved cortical somatosensory evoked potentials in apnoeic coma with loss of brain-stem reflexes: case report

A comatose patient suffering from diffuse cerebellar haemorrhage developed apnoea and brainstem areflexia, i.e. the clincial signs of brain death. However, median nerve somatosensory evoked potential testing 2.5 h and 22 h after the onset of this clinical syndrome showed cortical potentials partly preserved; these were abolished 46 h after the beginning of the clinical signs of brain death. This case report underlines the need for electrophysiological confirmation of brain death in patients with primarily infratentorial lesions.