Polyamine inhibition preserves somatosensory evoked potential activity after transient cerebral ischaemia

We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is related to deficits in electrocortical function as measured by somatosensory evoked potential (SEP). Adult Mongolian gerbils were anaesthetized with ketamine and prepared for monitoring SEP, cerebral blood flow (CBF) in parietal and frontal regions by H₂ clearance, and for bilateral carotid artery occlusion (BCO). Seven animals served as controls and received saline. Another 7 animals were treated with the ornithine decarboxylase inhibitor; difluoromethyl-ornithine (DFMO) (100 mg/kg I.P.) just prior to 40 min BCO followed by 4 h reperfusion. With BCO, both CBF and SEP declined significantly. In control animals, CBF fell from basal 37.8 ± 4.7 cc/100 g/min to 2.9 ± 1.2 cc/100 g/min and recovered to 22.7 ± 3.5 cc/100 g/h over the 4 h reperfusion period. DFMO treatment did not alter this CBF pattern. SEP amplitude declined to 11.3 ± 3.2% basal during occlusion. DFMO preserved SEP during ischaemia (35.5 ± 16.8% basal) and remained significantly more preserved during reperfusion (p > 0.05). These results suggest that polyamines are involved in the progressive decline in neuroelectrical function which occurs during occlusion/reperfusion in the Mongolian gerbil. The observation that polyamine inhibition preserves electrical function despite not altering blood flow indicates that the effects of polyamines are not manifested at the level of the vasculature but perhaps at the neuronal membrane.     

Measurement of somatosensory evoked potential in the Mongolian gerbil: the effects of cerebral ischaemia

Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemia following bilateral carotid artery occlusion (BCO) were characterized in the Mongolian gerbil. BCO significantly decreased cerebral blood flow (CBF). Reperfusion CBF at 10 min and 2, 3 and 4 h was significantly below preischaemic control values. BCO decreased SEP amplitude but had no effect on EP-P3 central conduction time. BCO did significantly increase EP-P11 central conduction time. Reperfusion amplitudes at 10 min and 2, 3 and 4 h revealed a significant increase only at 4 h when compared to the ischaemic amplitude. EP-P11 central conduction time at 10 min reperfusion showed dramatic improvement compared to ischaemic values, although values at 2, 3 and 4 h reperfusion were not statistically different from ischaemic values. A separate group of animals prepared identically but without BCO showed no significant changes in either SEP or CBF over time. These studies establish the protocol necessary to measure SEP in the Mongolian gerbil. In the future SEP may be used as an integral tool in the study of the primary determinants of neurophysiological recovery following cerebral ischaemia.     

Measurement of somatosensory evoked potential in the Mongolian gerbil: the effects of cerebral ischaemia

Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemia following bilateral carotid artery occlusion (BCO) were characterized in the Mongolian gerbil. BCO significantly decreased cerebral blood flow (CBF). Reperfusion CBF at 10 min and 2, 3 and 4 h was significantly below preischaemic control values. BCO decreased SEP amplitude but had no effect on EP-P₃ central conduction time. BCO did significantly increase EP-P₁₁ central conduction time. Reperfusion amplitudes at 10 min and 2, 3 and 4 h revealed a significant increase only at 4 h when compared to the ischaemic amplitude. EP-P₁₁ central conduction time at 10 min reperfusion showed dramatic improvement compared to ischaemic values, although values at 2, 3 and 4 h reperfusion were not statistically different from ischaemic values. A separate group of animals prepared identically but without BCO showed no significant changes in either SEP or CBF over time. These studies establish the protocol necessary to measure SEP in the Mongolian gerbil. In the future SEP may be used as an integral tool in the study of the primary determinants of neurophysiological recovery following cerebral ischaemia.     

Changes of somatosensory evoked potential accompanying ischaemia and hypoxia in cats

Changes of evoked potential accompanying haemorrhagic hypotension and hypoxia were investigated on cats to evaluate the usefulness of SEP as a monitor in an intensive care unit (ICU), and the following results were obtained. (1) Positive-negative diphasic potential was elicited at posterior sigmoid gyrus (PSG) by contralateral superficial radial nerve stimulation.

This potential was recorded at the restricted area of the posterior border of PSG and regarded as primary somatosensory evoked potential. (2) In the initial stage of haemorrhagic hypotension, both positive and negative components of SEP occasionally increased in amplitude. In profound hypotension in which CBF fell to less than the critical level of 30 ml 100 g^–1 min^–1, the latency was retarded and the amplitude was decreased. At CBF less than 10 ml 100 g^–1 min^–1, SEP disappeared. Within the range of CBF between 10 and 30 ml 100 g^–1 min^–1, a close correlation was noted between CBF and SEP amplitude. Transient increase of SEP amplitude was also observed during hypoxia induced by inhalation of nitrogen gas. (3) In normal state SEP was decreased in amplitude by conditioning stimulation of the nucleus lateralis posterior (LP nucleus) of the thalamus. This might be explained by the fact that intracortical inhibitory interneurons were activated by stimulation of LP nucleus, After haemorrhagic hypotension and hypoxia, however, the inhibitory effect on SEP elicited by LP nucleus stimulation attenuated or disappeared. Because of the initial impairment of the inhibitory interneurons by ischaemia and hypoxia, the amplitude of SEP might increase transiently.

In conclusion, the authors thought that SEP might be less useful than EEC in ICU, because of its insensible change to hypoxia and ischaemia.     

Changes of somatosensory evoked potential accompanying ischaemia and hypoxia in cats

Changes of evoked potential accompanying haemorrhagic hypotension and hypoxia were investigated on cats to evaluate the usefulness of SEP as a monitor in an intensive care unit (ICU), and the following results were obtained. Positive-negative diphasic potential was elicited at posterior sigmoid gyrus(PSG) by contralateral superficial radial nerve stimulation. This potential was recorded at the restricted area of the posterior border of PSG and regarded as primary somatosensory evoked potential. In the initial stage of haemorrhagic hypotension, both positive and negative components of SEP occasionally increased in amplitude. In profound hypotension in which CBF fell to less than the critical level of 30 ml 100 g-1 min-1, the latency was retarded and the amplitude was decreased. At CBE less than 10 ml 100 g-1 min-1, SEP disappeared. Within the range of CBF between 10 and 30 ml 100 g-1 min, a close correlation was noted between CBF and SEP amplitude. Transient increase of SEP amplitude was also observed during hypoxia induced by inhalation of nitrogen gas. (3) In normal state SEP was decreased in amplitude by conditioning stimulation of the nucleus lateralis posterior (LP nucleus) of the thalamus. This might be explained by the fact that intracortical inhibitory interneurons were activated by stimulation of LP nucleus. After haemorrhagic hypotension and hypoxia, however, the inhibitory effect on SEP elicited by LP nucleus stimulation attenuated or disappeared. Because of the initial impairment of the inhibitory interneurons by ischaemia and hypoxia, the amplitude of SEP might increase transiently. In conclusion, the authors thought that SEP might be less useful than EEG in ICU, because of its insensible change to hypoxia and ischaemia.     

Recovery of somatosensory evoked potential amplitude after movement

Sensory transmission is known to be impaired during movement of the stimulated body part. The goal of this study was to determine whether sensory gating persists for a measurable time after completion of a voluntary movement. Tactile stimuli were applied to the right index fingertip at intervals ranging from 63 to 1,000 msec after the completion of rapid thumb movement. Somatosensory evoked potentials (SEPs), recorded over the left cerebral hemisphere, were found to be reduced in size for at least 500 msec after the cessation of movement. The prolonged attenuation of SEPs after movement appears to depend on a central process that persists for a measurable time after the movement has ended.     

New subcortical components of the cerebral somatosensory evoked potential in man

Two new components of the human SEP upon stimulation of the contralateral median nerve at the wrist have been identified. Such components have been called N₁₆ and N₁₇, according to their polarity and latency. N₁₆ and N₁₇, as well as the N₁₄-P₁₅ complex, are generated by separate subcortical dipoles. Particularly, they are supposed to be far-field reflections of the activity of the dorsal columns nuclei or the medial lemniscus (N₁₄-P₁₅), the thalamus (N₁₆) and the thalamo-cortical radiation (N₁₇). Moreover, it has been established that N₁₄ is the very first intracranial component of the human SEP, the main peak of S wave and the preceding ones being extracranial in origin.
A new classification of SEP intracranial components including early (N₁₄ through N₁₇), intermediate (N₂₀ through P₃₀) and late events is proposed.     

Short-latency somatosensory evoked potential and event-related potential in patients with multiple cerebral infarcts.

Although the short-latency somatosensory evoked (SSEPs) and the cognitive event-related potentials (ERPs) have been found to change in patients with cerebral vascular disease, the relationship between these parameters has yet to be determined. For clarification of this relationship, SSEPs and ERPs were measured in 33 patients with multiple cerebral infarcts (MCI) and 25 age-matched normal subjects. ERPs were recorded during auditory discrimination tasks. The latency of P300 from the Pz region was measured. SSEPs evoked by median nerve stimulation were recorded from the second cervical vertebra and contralateral primary somatosensory cortex with a midfrontal reference. The central conduction time (CCT), the interpeak latency between N13 and N20, was measured. P300 latency in patients with MCI was significantly longer than that of the normal subjects. Patients with MCI also showed longer CCT than the normal subjects. CCT and P300 latency were significantly correlated in patients with MCI. This correlation was not found in normal subjects. From these results, the severity of the lesion with respect to SSEPs appears related to the prolongation of P300 latency in patients with MCI.     

Maturation of cerebral somatosensory evoked potentials

Cerebral somatosensory evoked potentials (SEPs) were elicited by stimulation of the median nerve and/or posterior tibial nerve in 117 children of 1 day to 16 years old. A major negative wave (N) was consistently recorded from the parietal region of the scalp when the arm was stimulated. The peak latency, the onset latency, the rising time and the duration of H wave are closely correlated with age and body length. The latencies are shortest in the subjects of 1-3 years old. SEPs to lower extremity stimulation were inconstant in the infants before the age of one. The major positive wave (P) has a variable topographic distribution along the middle line, over the scalp. The latencies are also very variable in the different subjects of the same age as well as in the same subject with different locations of active electrode. Among the parameters studied as for N wave, only the rising time of P wave is significantly correlated with age. The latencies of P wave have the shortest value in the subjects of 1-3 years old. The comparison of SEPs to upper and to lower limb stimulations shows that there is no relationship between them in respect to their morphology and amplitude. The minimum value of the latencies of N and P waves was observed at the same age but the difference between the peak latencies of P and N waves in the same subject increases considerably after 2 years of age and reaches the adult value after 5 years of age. These resultats indicate that the maturation of the peripheral somatosensory pathways proceeds at a higher rate than that of the central somatosensory pathways, that the maturation of the somatosensory pathways of the upper limb precedes that of the lower limb, and that the rising time of N or P waves is a good index of cortical maturation. The clinical utility of these SEPs in pediatrics is discussed.     

Comparison of the effects of ischaemia on early components of the somatosensory evoked potential in brainstem, thalamus, and cerebral cortex

In 14 ventilated, normocapnic baboons anaesthetised with alpha-chloralose, local CBF (hydrogen clearance) and the amplitude and latency of local components of the somatosensory evoked potential (SEP, median nerve stimulation) were measured bilaterally in ventrobasal thalamus (VPL), medial lemniscus (ML), and cerebral cortex before and during progressive ischaemia, produced by occlusion of the right middle cerebral artery and subsequent controlled reductions in mean systemic blood pressure (MSBP). The first significant reduction from control of the left cortical SEP amplitude occurred in the range of 30-40 mm Hg MSBP, but those of the VPL and ML responses only below 30 mm Hg; in the range of 20-30 mm Hg, the average SEP amplitudes in cortex, VPL, and ML were 8.6, 72.6, and 90.7% of control, respectively. In terms of local CBF, the cortical SEP threshold was in the range of 15-20 ml/100 g/min (as in previous work), that of VPL in the range of 10-15 ml/100 g/min, but the ML response was only markedly reduced below 10 ml/100 g/min. Thus, the differential ischaemic sensitivity of the SEP between the three regions was clearly demonstrated. These results indicate that as one descends the neuraxis, there is an increasing resistance of electrophysiological function to systemic hypotension, together with a decreasing threshold for local ischaemia.     

Brain ornithine decarboxylase activity following transient cerebral ischaemia: relationship to cerebral oedema development

Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38 degrees C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain was rapidly removed and forebrain samples analysed for ODC activity (enzymatic assay) and cerebral oedema (gravimetric determination). Marked loss of EEG amplitude was noted in all gerbils subjected to bilateral carotid artery occlusion. Ischaemia produced significant levels of cortical oedema throughout the reperfusion period (maximal decrease in specific gravity at 4 h postischaemia; control: 1.0456 +/- 0.0013; ischaemia: 1.0355 +/- 0.0021, mean +/- SD; p less than 0.0001). Significant subcortical oedema was produced at 10 min, 2 and 4 h postischaemia. A biphasic response was observed in brain ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain ornithine decarboxylase activity following transient cerebral ischaemia: relationship to cerebral oedema development

Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38°C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain was rapidly removed and forebrain samples analysed for ODC activity (enzymatic assay) and cerebral oedema (gravimetric determination). Marked loss of EEG amplitude was noted in all gerbils subjected to bilateral carotid artery occlusion. Ischaemia produced significant levels of cortical oedema throughout the reperfusion period (maximal decrease in specific gravity at 4 h postischaemia; control: 1.0456 ± 0.0013; ischaemia: 1.0355 ± 0.0021, mean ± SD; p > 0.0001). Significant subcortical oedema was produced at 10 min, 2 and 4 h postischaemia. A biphasic response was observed in brain ODC activity. Throughout the first 2 h of reperfusion, ODC activity was significantly depressed in ischaemic versus control animals (10 min: 1423 ± 824 versus 3049 ± 1019; 1 h: 704 ± 635 versus 2621 ± 902; 2 h: 348 ± 184 versus 3654 ± 2072 pmoles/g tissue/60 min; p > 0.05). This difference was no longer detectable by 4 h postischaemia and by 6 h, ODC levels were significantly higher in ischaemic animals (ischaemia: 9314 ± 2652; control: 3065 ± 2000 pmoles/g tissue/60 min; p > 0.01). Although not significant, ODC was also greater in ischaemic animals at 8 h postischaemia. ODC levels at 6 and 8 h postischaemia were significantly higher (p > 0.05) than ODC levels at 10 min, 1 and 2 h postischaemia among ischaemic animals. These data indicate that transient ischaemia initially suppresses then stimulates ODC activity over the initial 8 h following transient global ischaemia in the gerbil. Since stimulation of ODC activity does not occur until early cerebral oedema is established, it is unlikely that polyamines are involved in the early cytotoxic oedema. Later stages of ischaemic oedema, however, with mixed cytotoxic and vasogenic components may be affected by the delayed rise in ODC activity after transient ischaemia.     

Short latency somatosensory evoked potential in children

The short latency somatosensory evoked potential was studied in 90 normal children of 1 month to 16 years old and 7 adults. Somatosensory stimuli were delivered through a disc electrode placed over the median nerve at the wrist joint. The uniform recording sites used were the central region of the scalp, and the seventh cervical spine or Erb's point. Reference electrodes were placed on the hand contralateral to the median nerve stimulated. Three positive peaks (P1, P2 and P3) and one negative peak (N1) were consistently recorded, a further positive peak (P4) after N1 was not always observed. The latency of each peak per 1 m body length decreased with age until 2 or 5 years of age. The latency of each peak after 2 years of age was positively correlated with the body length and arm length. The value of P1 peak latency per 1 m body length reaches adult values at an earlier rate than the value of P3 peak latency and P2-P3 latency per 1 m body length. This suggests that central lemmiscal pathways mature at a slower rate than peripheral nerve fibers. The wave form pattern of the short latency somatosensory evoked potential changed to the adult pattern at 10 years of age. The peak latency of P4 during deep sleep was slightly prolonged. In recording on infants during sleep, the EEG should be monitored to determine the stage of sleep.     

Effect of ischaemia on somatosensory evoked potentials in diabetic patients.

The nerve action potential at the elbow and somatosensory evoked potentials (SEPs) at the scalp were recorded over 30 minutes of tourniquet-induced limb ischaemia in 10 diabetic patients and 10 controls. According to the SEP changes, an increased resistance to nerve ischaemia in diabetic patients was observed. The pathways involved in SEP conduction are discussed.     

Electroencephalogram and somatosensory evoked potential changes after administration of six convulsant drugs

Electrophysiological effects of convulsant drugs in mammalian brain have been reported, but it has not been clear whether the changes described were indicative of general increases in neuronal excitability or whether they varied as a function of the different modes of convulsant action. Cats with chronically implanted electrodes were administered intraperitoneal injections of six convulsant drugs: allylglycine, bemegride, bicuculline, picrotoxin, pentylenetetrazol, and strychnine. The electroencephalogram (EEG) was monitored continuously and somatosensory evoked potentials were elicited during the period to seizure onset. Enhancement of the primary response of the evoked potentials recorded at the cortex paralleled the increases in EEG paroxysmal activity. Both EEG and evoked potential changes were regarded as indicating general preseizure excitability rather than varying with the presumed mechanisms of the individual drugs.     

Frontal component of the somatosensory evoked potential

Electric stimulation of the median nerve at the wrist evokes a series of electric potentials that can be recorded from the scalp or directly from the cortex. These somatosensory evoked potentials (SEP) include a parietal negativity with a maximum 20 ms after the stimulus, which originates in the somatosensory cortex, probably area 3b (Allison et al. [1991a], Brain 114:2465–2503 and Desmedt et al. [1987], Electroenceph Clin Neurophysiol 68:1–19). Thirty milliseconds after the stimulus, a negative potential (N30) occurs at frontal recording sites. Recently it was observed that the amplitude of this potential is altered in patients with dystonia, Parkinson's disease, and Huntington's chorea. It has been argued that the N30 potential stems from cortical areas other than the somatosensory cortex, for example, the supplementary motor area. We used multichannel recordings to investigate the scalp distribution of the N20 and the N30 potentials in healthy subjects. We found that the N20 as well as the N30 potentials were accompanied by a corresponding positivity at frontal and parietal recording sites, respectively. The N20/P20 and the N30/P30 potential fields had a mirrorlike appearance, and both showed a polarity reversal near the central sulcus. This and the results of correlation analyses led us to the conclusion that the N30 generator is located near the central sulcus. © 1995 Wiley-Liss, Inc.     

Dermatomal somatosensory evoked potential demonstration of nerve root decompression after VAX-D therapy

Abstract

Reductions in low back pain and referred leg pain associated with a diagnosis of herniated disc, degenerative disc disease or facet syndrome have previously been reported after treatment with a VAX-D table, which intermittently distracts the spine. The object of this study was to use dermatomal somatosensory evoked potentials (DSSEPs) to demonstrate lumbar root decompression following VAX-D therapy. Seven consecutive patients with a diagnosis of low back pain and unilateral or bilateral L5 or S1 radiculopathy were studied at our center. Disc herniation at the L5-S1 level was documented by MRI or CT in all patients. All patients were studied bilaterally by DSSEPs at L5 and S1 before and after VAX-D therapy. All patients had at least 50% improvement in radicular symptoms and low back pain and three of them experienced complete resolution of all symptoms. The average pain reduction was 77%. The number of treatment sessions varied from 12 to 35. DSSEPs were considered to show improvement if triphasic characteristics returned or a 50% or greater increase in the P1-P2 amplitude was seen. All patients showed improvement in DSSEPs after VAX-D therapy either ipsilateral or contralateral to the symptomatic leg. Two patients showed deterioration in DSSEPs in the symptomatic leg despite clinically significant improvement in pain and radicular symptoms. Overall, 28 nerve roots were studied before and after VAX-D therapy. Seventeen nerve root responses were improved, eight remained unchanged and three deteriorated. The significance of DSSEP improvement contralateral to the symptomatic leg is emphasized. Direct compression of a nerve root by a disc herniation is probably not the sole explanation for referred leg pain. [Neurol Res 2001; 23: 706-714]