Sensory evoked potentials in Creutzfeldt-Jakob disease

Eight patients presenting with intermediate or terminal evolution of Creutzfeldt-Jakob disease (CJD) were investigated by means of evoked potentials. Fifteen age-matched healthy subjects served as controls. The 8 patients had well-recognizable but simplified flash evoked potentials (FEPs) consisting of P1 and N2 waves followed by a single late positive (P2) deflection. Enlarged FEPs were found in 2 of the 8 patients. The somatosensory central conduction time was normal in 3 of 5 patients, and it resulted in upper normal limits or was moderately slowed in 2 patients. No enlarged somatosensory scalp potentials were recorded. Cortical somatosensory responses were characterized by an unrecognizable (4 patients) or delayed (2 patients) N33 wave. Brainstem auditory evoked responses, recorded in 6 patients, were normal. In CJD very important functional impairment of the sensory cortical areas is associated with absent or mild dysfunction of the subcortical sensory pathways.     

Scalp topography of mechanically and electrically evoked somatosensory potentials in man

Scalp topography of somatosensory evoked potentials following mechanical (SEPs(M)) and electrical (SEPs(E)) stimulation of the left middle finger was investigated with linked ear reference in 21 normal young adults. A small plastic ball (touch) or needle (pain) was used for the mechanical stimulation. With mechanical stimulation, at least 3 positive and 3 negative potentials (P19(M), N24(M), P29(M), N36(M), P49(M) and N61(M] were found in the post-rolandic area contralateral to the stimulation. The wave form in SEPs(M) was similar to those in SEPs(E), but the peak latency of each component in SEPs(M) was 1-4 msec longer than that in SEPs(E). Earlier components such as P19(M), N24(M) and P29(M) were not as clearly recognized as corresponding components in SEPs(E). However, the wave form recorded on the hemisphere ipsilateral to the stimulation or in the frontal area contralateral to the stimulation showed a greater difference from subject to subject. P19(M), N24(M) and P29(M) correlated positively both with arm length and height of the subject. There was no significant difference of the wave form between the linked ear reference and the bipolar (C4-Fz) derivation. Wave form of SEPs(M) by needle stimulation did not significantly differ from that by plastic ball stimulation.     

Somatosensory evoked potentials after median and tibial nerve stimulation in healthy newborns.

Cortical and spinal somatosensory evoked potentials (SEPs) have been recorded after median and tibial nerve stimulation in healthy newborns. Spinal SEPs were readily obtained and recorded in all but one neonates after stimulation of both nerves. Cortical SEPs were more frequently recorded after median nerve (87%) than after tibial nerve stimulation (73%) but the shape of cortical SEPs obtained after tibial nerve stimulation was less variable. The mean feature of cortical SEPs was a negative wave (N27) for median nerve and a positive wave (P32) for tibial nerve. The present results demonstrate the feasibility of obtaining in the same baby, spinal and cortical SEPs after stimulation of median and tibial nerve, giving information on the functional integrity of central and peripheral somatosensory pathways which supply upper and lower limbs.     

Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans.

OBJECTIVE: To study the after-effect of transcranial direct current stimulation (tDCS) over the sensorimotor cortex on the size of somatosensory evoked potentials (SEPs) in humans. METHODS: SEPs were elicited by electrical stimulation of right or left median nerve at the wrist before and after anodal or cathodal tDCS in 8 healthy subjects. tDCS was applied for 10 min to the left motor cortex at a current strength of 1 mA. RESULTS: Amplitudes of P25/N33, N33/P40 (parietal components) and P22/N30 (frontal component) following right median nerve stimulation were significantly increased for at least 60 min after the end of anodal tDCS, whereas P14/N20, N20/P25 (parietal components) and N18/P22 (frontal component) were unaffected. There was no effect on SEPs evoked by left median nerve stimulation. Cathodal tDCS had no effect on SEPs evoked from stimulation of either arm. CONCLUSIONS: Anodal tDCS over the sensorimotor cortex can induce a long-lasting increase in the size of ipsilateral cortical components of SEPs. SIGNIFICANCE: tDCS can modulate cortical somatosensory processing in humans and might be a useful tool to induce plasticity in cortical sensory processing.     

Right or left ear reference changes the voltage of frontal and parietal somatosensory evoked potentials.

Short-latency cortical somatosensory evoked potentials (SEPs) to left median nerve stimulation were recorded with either the left or right earlobe as reference. With a right earlobe reference the voltage of the parietal N20 and P27 was reduced while the voltage of the frontal P20 and N30 was enhanced. The effects were consistent, but their size varied with the SEP component considered and also among the subjects. Analysis of SEPs at different scalp sites and at either earlobe suggested that the ear contralateral to the side stimulated picked up transient potential differences, depending a.o. on side asymmetry and geometry of the neural generators as disclosed in topographic mapping. For example, the right ear potential can be shifted negatively by the right N20 field evoked by left median nerve stimulation. The changes involve the absolute potential values, but not the time features or the gradients of potential fields. Scalp current density (SCD) maps are not affected. The results are pertinent for current discussions about which reference to use and document the practical recommendation of recording short-latency cortical SEPs with a reference at the ear ipsilateral (not contralateral) to the side of stimulation.     

Somatosensory evoked potentials (SEPs) and cortical single unit responses elicited by mechanical tactile stimuli in awake monkeys

The origins of surface recorded evoked potentials have been investigated by combining recordings of single unit responses and somatosensory evoked potentials (SEPs) from the postcentral gyrus of 4 alert macaque monkeys. Responses were elicited by mechanical tactile stimuli (airpuffs) which selectively activate rapidly adapting cutaneous mechanoreceptors, and permit patterned stimulation of a restricted area of skin. Epidurally recorded SEPs consisted of an early positive complex, beginning 8-10 msec after airpuff onset, with two prominent positive peaks (P15 and P25), succeeded by a large negative potential (N43) lasting 30 msec, and a late slow positivity (P70). SEPs, while consistent in wave form, varied slightly between monkeys. The amplitude of the early positive complex was enhanced by increasing the number of stimulated points, or by placing the airpuffs in the receptive fields of cortical neurons located beneath the SEP recording electrode. SEP amplitude was depressed when preceded 20-40 msec earlier by a conditioning stimulus to the same skin area. Single unit responses in areas 3b and 1 of primary somatosensory (SI) cortex consisted of a burst of impulses, beginning 11-12 msec after the airpuff onset, and lasting another 15-20 msec. Peak unitary activity occurred at 12-15 msec, corresponding to the P15 wave in the SEP. No peak in SI unit responses occurred in conjunction with the P25 wave. Although SI neurons fired at lower rates during P25, the lack of any peak in SI unit responses suggests that activity in other cortical areas, such as SII cortex, contributes to this wave. Most unit activity in SI cortex ceased by the onset of N43, and was replaced by a period of profound response depression, in which unit responses to additional tactile stimuli were reduced. We propose that the N43 wave reflects IPSPs in cortical neurons previously depolarized and excited by the airpuff stimulus. Late positive potentials (P70) in the SEP had no apparent counterpart in SI unit activity, suggesting generation at other cortical loci.     

Somatosensory evoked potentials in comatose patients: correlation with outcome and neuropathological findings

Summary Subcortical and early cortical somatosensory evoked potentials (SEPs) were recorded in 63 comatose patients and classified into five salient SEP grades, which were defined as follows: grade 1, normal SEP; grade 2, SEPs with a clearly recognizable scalp component N20, normal central conduction time but clearly distorted wave N20–P25; grade 3, SEPs with a still recognizable N20 but delayed central conduction time and severely altered wave N20–P25; grade 4, SEPs with absence of N20 but with a more or less recognizable P15; grade 5, SEPs with absence of both N20 and P15. When these five patterns were compared with outcome, it was found that bilaterally normal SEPs or only unilaterally distorted SEPs were generally followed by good outcomes. Bilaterally altered SEPs (grade 2 or 3) were indicative of reduced chances of full recovery. The great majority of patients showing either grade 4 or 5 SEPs died within a few days after the recording session. In 31 patients, it was found post mortem that grade-2 SEPs reflected cortical brain damage, whereas grade-3 SEPs correlated well with subcortical lesions. In post-traumatic patients, this SEP pattern coresponded to diffuse subcortical shearing lesions. Patients with grade 4 or 5 SEPs were found to have severe brain oedema giving rise to transtentorial herniation, which was combined with secondary midbrain haemorrhage and tonsillar herniation in all patients with bilateral grade-5 SEPs.     

Detection and peripheral or central localization of sensory pathway involvement of the lower limbs by somatosensory evoked potentials

In the presence of more or less atypical sensory or sensorimotor symptoms the questions that arise most frequently concern the authenticity of the disorders and the precise level of the lesion. In this study, somatosensory evoked potentials (SEPs) to stimulation of the tibial nerve at the ankle were recorded at different levels in 35 healthy subjects and 32 patients with sensory disorders. Recording electrodes were placed at the popliteal fossa (peripheral sensory nerve conduction velocity), at the T12-L1 level (medullary potential: N21) and at the vertex (P40 wave). The spine to cortex time interval was measured. A systematic study of evoked responses to median nerve stimulation was performed. The 32 patients were divided into 4 groups: Group I (3 cases) had slowed sensory conduction velocity (SCV), similar delay in N21 latency and normal N21-P40: peripheral neuropathy. Group II (4 cases) had normal SCV, delayed N21 latency and normal N21-P40: radicular or conus medullaris injury. Group III (19 cases) had normal SCV, normal N21 latency and lengthened N21-P40 interval. A study of responses to median nerve stimulation made it possible to discriminate between spinal and cortical or subcortical impairment. Group IV (6 cases) had abnormalities from any two of the three groups defined above. In 24 out of 32 patients (75 p. 100), further investigations (myelography, MRI, EMG) confirmed the localization determined by evoked responses. In the other 8 patients (25 p. 100) whose clinical picture suggested a medullary or radicular impairment, SEPs alone clearly revealed an injury. SEPs can distinctly show a spinal impairment and determine the choice of further investigations.     

Topography of somatosensory evoked potentials to median nerve stimulation in patients with cerebral lesions

Scalp distributions and topographies of early cortical somatosensory evoked potentials (SEPs) to median nerve stimulation were studied in 22 patients with 5 different types of cerebral lesion due to cerebrovascular disease or tumor (thalamic, postcentral subcortical, precentral subcortical, diffuse subcortical and parieto-occipital lesions) in order to investigate the origins of frontal (P20, N24) and central-parietal SEPs (N20, P22, P23). In 2 patients with thalamic syndrome, N16 was delayed in latency and N20/P20 were not recorded. No early SEP except for N16 was recorded in 2 patients with pure hemisensory loss due to postcentral subcortical lesion. In all 11 patients with pure hemiparesis or hemiplegia due to precentral subcortical lesion N20/P20 and P22, P23/N24 components were of normal peak latencies. The amplitude of N24 was significantly decreased in all 3 patients with complete hemiplegia. These findings support the hypothesis that N20/P20 are generated as a horizontal dipole in the central sulcus (3b), whereas P23/N24 are a reflection of multiple generators in pre- and post-rolandic fissures. P22 was very localized in the central area contralateral to the stimulation.     

The use of transcranial magnetic stimulation for monitoring descending spinal cord motor function.

This report describes our initial clinical experience using transcranial magnetic stimulation for monitoring spinal cord motor function during surgical procedures. Motor evoked potentials were elicited using a cap shaped coil placed on the scalp of 27 patients while recording peripheral motor responses (compound muscle action potentials--CMAPs) from the upper (N = 1) or lower limbs (N = 26). Wherever possible, cortical somatosensory responses (SEPs) were also monitored by electrically stimulating the left and right posterior tibial nerve (N = 25) or the median nerve (N = 1). The judicious choice of anesthetic regimens resulted in successfully obtaining motor evoked responses (MEPs) in 21 of 27 patients and SEPs in 26 of 27 patients. Single pulse TMS resulted in peripheral muscle responses having large variability, whereas, the variability of SEPs was much less. Criteria based on response variability for assessing clinically significant changes in both MEPs and SEPs resulted in two false negative predictions for SEPs and none for MEPs when evaluating postoperative motor function. We recommend monitoring both sensory and motor pathways during procedures where placing the spinal cord at risk of damage.     

Frequency-dependent changes in cerebral blood flow and evoked potentials during somatosensory stimulation in the rat.

Contrary to the concept of neuronal-vascular coupling, cortical evoked potentials do not always correlate with blood flow responses during somatosensory stimulation at changing stimulus rates. The goal of this study is to clarify the effects of stimulus frequency on the relationship between somatosensory evoked potentials (SEPs) and cerebral blood flow. In rats anesthetized with alpha-chloralose, we measured SEPs by signal-averaging field potentials recorded with an electrode placed on dura overlying the hindlimb somatosensory cortex. Regional blood flow was simultaneously assessed in the same region with a laser-Doppler flow (LDF) probe. The contralateral sciatic nerve was stimulated with 0.1 A pulses at the frequencies of 1, 2, 5, 10 and 20 Hz. SEPs (both P1 and N1 components) declined with increasing frequency regardless whether stimulus duration (20 s) or number (100) were kept constant, suggesting that frequency is an important determinant of neuronal activity. In contrast, LDF responses increased to a maximum at 5 Hz, and do not correlate with SEPs. Because CBF should reflect integrated neuronal activity, we computed the sum of SEPS (summation operatorSEP = SEP x stimulus frequency) as an index of total neuronal activity at each frequency. Summation operatorSEP indeed correlates positively (P<0.001) with LDF responses. Thus, during somatosensory stimulation at various frequencies, cerebral blood flow is coupled to integrated neuronal activity but not to averaged evoked potentials.     

Brain stem auditory, visual and somatosensory evoked potentials in leukodystrophies

Brain stem auditory (BAERs), visual (VEPs) and somatosensory evoked responses (SEPs) were recorded in 12 patients with Pelizaeus-Merzbacher leukodystrophy (PMD), three with adrenoleukodystrophy (ALD) and three with metachromatic leukodystrophy (MLD). All the 3 evoked responses were abnormal in all patients except normal VEPs and SEPs in a patient with early ALD. In most patients wave I with and without wave II were the only components of the BAERs that remained, subsequent components (waves III-VII) were absent. VEPs were severely altered; either no identifiable response to flash or pattern reversal stimuli could be recorded or the major components were significantly delayed in latency. Short latency SEPs following median nerve stimulation usually showed a normally recorded Erb's potential (N10), but an absence or marked attenuation of cervical (N14) and early scalp components (N19 and P22) or the occurrence of the scalp components with a significant delay. Multimodality evoked responses provide more information regarding the functional integrity of several afferent systems in patients with white matter disorders.     

The assessment of severe head injury by short-latency somatosensory and brain-stem auditory evoked potentials

The relative prognostic value of short-latency somatosensory evoked potentials (SEPs) and brain-stem auditory evoked potentials (BAEPs) was assessed in 35 patients with post-traumatic coma. Analysis of the evoked potentials was restricted to those recorded within the first 4 days following head injury. Abnormal SEPs were defined as an increase in central somatosensory conduction time or an absence of the initial cortical potential following stimulation of either median nerve. Abnormal BAEPs were classified as an increase in the wave I-V interval or the loss of any or all of its 3 most stable components (waves I, III and V) following stimulation of either ear. SEPs reliably predicted both good and bad outcomes. All 17 patients in whom SEPs were graded as normal had a favourable outcome and 15 of 18 patients in whom SEPs were abnormal had an unfavourable outcome. Although abnormal BAEPs were associated with an unfavourable outcome in almost all patients (6 of 7), only 19 of 28 patients with normal BAEPs had a favourable outcome. The finding of normal BAEPs was therefore of little prognostic significance. These results confirm the superiority and greater sensitivity of the SEP in detecting abnormalities of brain function shortly after severe head trauma.     

Neurophysiological study in Pelizaeus-Merzbacher disease

The neurophysiological characteristics of Pelizaeus-Marzbacher disease (PMD) were studied in four Japanese patients aged between 5 and 13 years. Pendular spontaneous nystagmus was always recorded with a frequency between 2.5 and 4 Hz, and abnormal saccades with an almost twofold prolongation in onset time and 50% decrease in velocity were noted. Brainstem auditory evoked potentials consistently demonstrated severely altered waves II to V, following a normal wave I, despite normal hearing acuity. Somatosensory evoked potentials (SEPs) were always absent between brainstem components and early cortical responses. Late cortical components of SEPs and visual evoked potentials with significantly prolonged latencies were recorded in the three younger cases having normal sensory and visual acuity (N35 of SEP, 73.1 ± 2.1 ms; N75 of VEP, 129.0 ± 12.7 ms; mean ± S.D.), while these peaks were absent in the oldest case having the most severe handicap. In motor evoked potentials (MEPs), R1 of blink reflex with significantly prolonged latency (14.9 ± 1.48 ms) was always obtained, and no subsequent R2 was elicited. Magnetic transcortical stimulation elicited no MEPs of the thenar even in the facilitating condition on voluntary contraction despite mild weakness of the thenar, while normal MEPs were always elicited on cervical stimulation. These electrophysiological findings were consistent with extensive conduction slowing involving the brainstem to the cerebrum, which seemed to be accompanied by conduction block in motor systems rather than sensory systems. Although each of the results was not specific, in combination they suggested the characteristics of diffuse brain dysmyelination in PMD.     

Tumors localized near the central sulcus may cause increased somatosensory evoked potentials.

OBJECTIVE: Median nerve somatosensory evoked potentials (SEPs) may be altered in patients with cerebral tumors. In rare cases cortical responses may be increased, but the significance of this finding remains unclear. METHODS: We investigated 3 patients in whom an epileptic seizure was the only neurological symptom of a cerebral tumor located near the central sulcus. We studied median nerve SEPs, motor evoked potentials in abductor digiti minimi muscle, and long-loop reflexes in abductor pollicis brevis muscle bilaterally. Two patients also underwent intraoperative neurophysiological monitoring. RESULTS: All 3 patients presented with enlarged cortical SEPs on the side of the brain tumor. The responses increased further post-operatively, and the enhancement persisted in follow-up examinations up to 6 months after surgical tumor extirpation. Intraoperative monitoring documented a substantial increase of the enlarged potential N20-P22 during tumor removal in one patient, who also presented with an exaggerated long-loop reflex on the tumor side. Transcranial magnetic stimulation revealed unremarkable motor evoked potentials in all 3 patients. CONCLUSIONS: Distinct mechanisms must be considered in order to explain both immediate and long-term changes of neuronal excitability leading to increased cortical SEPs. SIGNIFICANCE: Hyperexcitability of cortical neurons or insufficient cortical inhibitory mechanisms may be responsible for increased SEPs, which may serve as an epileptic marker in patients suffering from a tumor near the central sulcus.     

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.     

Scalp-recorded short and middle latency peroneal somatosensory evoked potentials in normals: comparison with peroneal and median nerve SEPs in patients with unilateral hemispheric lesions

Peroneal somatosensory evoked potentials (SEPs) were performed on 23 normal subjects and 9 selected patients with unilateral hemispheric lesions involving somatosensory pathways. Recording obtained from right and left peroneal nerve (PN) stimulations were compared in all subjects, using open and restricted frequency bandpass filters. Restricted filter (100-3000 Hz) and linked ear reference (A1-A2) enhanced the detection of short latency potentials (P1, P2, N1 with mean peak latency of 17.72, 21.07, 24.09) recorded from scalp electrodes over primary sensory cortex regions. Patients with lesions in the parietal cortex and adjacent subcortical areas demonstrated low amplitude and poorly formed short latency peroneal potentials, and absence of components beyond P3 peak with mean latency of 28.06 msec. In these patients, recordings to right and left median nerve (MN) stimulation showed absence or distorted components subsequent to N1 (N18) potential. These observations suggest that components subsequent to P3 potential in response to PN stimulation, and subsequent to N18 potential in response to MN stimulation, are generated in the parietal cortical regions.     

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.     

Cortical somatosensory evoked potentials to posterior tibial nerve stimulation in newborn infants

Successful cortical recordings of somatosensory-evoked potentials (SEPs) to posterior tibial nerve (PTN) stimulation were obtained in 21 (87.5%) for P1 and 22 (91.7%) for N1 of 24 infants who were followed up for at least 3 years and had a normal outcome. There were linear decreases with increasing post menstrual age in both P1 and N1 peak latency. Of the four cases with diplegia later, three showed definite abnormalities, no responses and delayed latency in PTN SEPs respectively, however, the other case showed normal responses. Of the three cases with mental retardation, two showed relatively long latency and borderline responses respectively, and the other case showed normal responses. As the pathway of PTN SEPs traverses the periventricular area of the brain likely to be affected by ischemic lesions in premature infants, abnormalities in the responses might indicate a later motor disorder.     

Short- and long-latency tibial somatosensory evoked potentials in cerebral lesions affecting rolandic leg areas

Summary Short- and long-latency tibial somatosensory evoked potentials (SEPs) were studied in nine patients with clinical presentation primarily involving one lower extremity. In group 1, with extensive infarcts in the territory of anterior cerebral artery, tibial cortical SEPs were uniformly absent. In group 2, with small infarcts involving Rolandic leg areas, tibial SEPs showed a decrease in overall response amplitude and attenuation of P40. In group 3, with discrete mass lesions compressing Rolandic leg areas, P40 was preserved but might be delayed. Late SEP components (N75, P100 and N135) tended to be preserved in the patients of group 2 and 3. The data suggest that Rolandic leg areas and the neighboring cortex are crucial for short- and long-latency tibial cortical SEPs and that small lesions affecting Rolandic leg areas tend to affect short-and mid-latency SEP components.