FVEPs in Creutzfeldt-Jacob disease: waveforms and interaction with the periodic EEG pattern assessed by single sweep analysis.

OBJECTIVE: To characterise flash visual evoked potentials (FVEPs) in 20 patients with Creutzfeldt-Jacob disease (CJD), and assess the relationships between spontaneous EEG patterns and the responses to individual stimuli. METHODS: We analysed the shape and time course of periodic sharp wave complexes (PSWCs) and responses to 1 Hz flashes. In nine patients, we applied an algorithm based on an autoregressive model with exogenous input (ARX) to estimate responses to individual random flashes and their interaction with PSWCs. RESULTS: The FVEPs included P1 and N1 components in all patients, and the P2 peak in 18. Eight patients showed giant FVEPs (N1-P2>60 V), all of whom had an MM polymorphism in codon 129 of the prion protein gene; in seven cases, the presence of giant FVEPs correlated with a prominent and almost continuous periodic EEG pattern. Giant N1-P2 abnormally spread on the anterior scalp regions, and had a different waveform distribution from that of the PSWCs. In five patients with a normal or slightly enlarged average N1-P2 amplitude, single sweep (ARX) analysis revealed a period of relative refractoriness following individual PSWCs. In four patients with 'giant' FVEPs, the individual responses occurred regardless of the interval between the stimulus and previous PSWC, but their amplitude had an inverse relationship with the interval length. CONCLUSIONS: Giant responses to flash stimuli are a common finding in CJD patients (40% of our cases). Single sweep ARX analysis showed that PSWCs were followed by a period of partial refractoriness, which prevented most of the individual responses to flashes, but not giant FVEPs. The association between prominent spontaneous paroxysms and giant FVEPs suggests that both are due to a common hyperexcitable change favouring neuronal synchronisation. SIGNIFICANCE: Our data contribute to clarifying the debated problem of the occurrence of giant FVEPs in CJD and their relationships with the spontaneous periodic EEG pattern.     

Patterns of disturbed impulse propagation in multiple sclerosis identified by low and high frequency somatosensory evoked potential components.

In human median nerve somatosensory evoked potentials (SSEPs), high frequency (600 Hz) oscillations (HFOs) are superimposed onto the low frequency SSEP component N20. High frequency oscillations are generated both in deep axon segments of thalamo-cortical projection neurons and at the primary somatosensory cortex. The present study aimed to test the hypothesis that HFOs might be more sensitive to temporal dispersion caused by demyelinating lesions in multiple sclerosis (MS) than the N20. The authors recorded HFOs in median nerve SSEPs in 50 patients with definite MS and in 30 healthy controls. Three patterns of SSEP alterations were found: (1) abolished HFOs with either normal (11% of stimulated limbs), or delayed N20 (16% of stimulated limbs); (2) an attenuation of N20 amplitude with preserved HFOs (13%); and (3) a mixture of both patterns (21%). The first pattern--normal N20 with abolished HFOs--indicates that the HFOs are a sensitive marker of slight demyelination. The second pattern is suggestive of a mainly axonal lesion type, while the third pattern points to a combined axonal/demyelinating process or a conduction block. Analysis of HFOs allows identification of slight demyelinating processes in MS patients in whom the N20 SSEP component remains unaffected. The HFOs provide a tool to distinguish different patterns of disturbed impulse propagation.     

Amantadine sulfate infusion effect on N30 somatosensory evoked potentials in Parkinson's disease

The purpose of this study was to evaluate the effect of amantadine sulfate infusion on the N30 component of the median nerve short-latency somatosensory evoked potentials (SSEPs) in patients with Parkinson's disease (PD). Twenty patients with advanced PD and severe motor fluctuations received a 6-day course of amantadine sulfate infusion (400 mg/day) plus their usual levodopa medication. Patients were assessed clinically by means of the Unified Parkinson's Disease Rating Scale (UPDRS-III and -IV). SSEPs to median nerve stimulation were recorded from the parietal and frontal regions before and after the 6-day course of amantadine infusion. Mean UPDRS motor score during the ON and OFF phase improved after amantadine infusion, as did motor fluctuations. SSEP changes resulting from amantadine sulfate treatment were observed in the P20-N30 amplitude as follows: Mean P20-N30 amplitudes before and after treatment were 2.15 +/- 1.11 microV and 3.06 +/- 1.19 microV respectively (p = 0.000), whereas mean N30-P40 amplitude increased from 2.7 +/- 1.6 microV to 3.9 +/- 1.3 microV after treatment (p = 0.000). Our results indicate that coincident to its clinical impact, amantadine infusion in patients with PD affects electrophysiologic parameters as well.     

Median nerve somatosensory evoked potentials in patients with lacunar and other small subcortical strokes

We recorded median nerve somatosensory evoked potentials (SSEPs) in 42 patients with small subcortical strokes associated with lacunar syndromes. Seventeen patients had abnormal SSEPs. The P22 component was most often affected; changes in N20 and N18 were less common. Four patients with pure motor strokes (PMS) had abnormal SSEPs. Abnormalities of P22 correlated best with motor findings; those of N20 with sensory signs and symptoms. Similar SSEP abnormalities were produced by lesions in various locations. P22 and N20 abnormalities occurred independently and together. We conclude: (1) abnormal SSEPs are common in patients with small subcortical strokes associated with lacunar syndromes, including pure motor stroke; (2) P22 and N20 have separate cortical generators; and (3) P22 may be generated within sensory pathways which are adjacent to or influenced by motor pathways.     

Estimation of cervical cord dysfunction by somatosensory evoked potentials

The purpose of this study was to examine the relationship of abnormal short-latency somatosensory evoked potentials (SSEPs) recorded by a noncephalic reference montage with clinical variables in cervical myelopathy patients and to reexamine the diagnostic utility of SSEPs in such patients. We studied cervical SSEPs elicited by stimulating the median and ulnar nerves in 87 patients. Our grade classification of spinal N13, which is based on the normal limits of latencies or amplitudes, corresponded well with the clinical variables and is of value when trying to localize the cervical lesion segmentally. The N9-P14 interpeak latency in response to ulnar nerve stimulation correlated well with lower extremity function (r = -0.440, P <0.0001). We suggest a combined assessment of N13 amplitude, and N9-N13 and N9-P14 interpeak latencies to estimate dorsal column and dorsal horn function separately in patients with cervical myelopathy.     

Evoked potentials in Huntington's disease. A comparative and longitudinal study

Pattern-reversal visual (PRVEPs), brain-stem auditory (BAEPs), and somatosensory (SSEPs) evoked potentials were studied in 12 patients with Huntington's disease (HD) and were repeated in eight at one and two years. The mean cortical SSEP amplitude was decreased compared with that of age-matched controls, with a trend of decreasing amplitude with increasing duration and severity of illness. The SSEP latency was not significantly different from that of controls. The PRVEPs and BAEPs were normal. The serial studies showed a progressive decrease in amplitude of the SSEP over a two-year period. These neurophysiological findings may reflect the pathological involvement of the thalamus reported for HD. While evoked potentials are not of use in individual case diagnosis, the SSEP may be an objective physiological method for following the course of the disease in HD and the effects of therapeutic intervention in patient populations.     

Utility of somatosensory evoked potentials in chronic acquired demyelinating neuropathy

Chronic acquired demyelinating polyneuropathy (CADP) is a heterogeneous syndrome that may be classified into a number of subtypes. Somatosensory evoked potentials (SSEPs) assess proximal segments of sensory nerves, inadequately assessed by routine nerve conduction studies (NCSs). The aim of the present study was to determine the utility of SSEPs in diagnosing and classifying different CADP subtypes. Forty-seven patients with CADP were studied and classified in five groups based on conventional NCSs and SSEPs. Some patients in Group 1 were initially misdiagnosed as having either motor neuron disease or multifocal motor neuropathy due to normal sensory NCSs, but they exhibited abnormal tibial and median nerve SSEPs, as evidenced by marked prolongation or absence of peripheral potentials (N9-median nerve, and N20-tibial nerve). These were reclassified as having chronic inflammatory demyelinating neuropathy (CIDP). In CIDP patients (Group 2), SSEPs were abnormal, thereby confirming the presence of demyelination in the proximal peripheral nerves. Patients with distal acquired demyelinating neuropathy (DADS) (Group 3), as defined by conventional NCS, exhibited abnormal SSEPs when anti-MAG antibodies were present. Anti-MAG-negative DADS patients (Group 3) had normal SSEPs. In the pure sensory ataxic group (Group 4), SSEP studies disclosed poorly formed and delayed cortical potentials with absent lumbar (N20) potentials, thereby suggesting the presence of proximal demyelination. SSEPs were normal in the pure motor CIDP and multifocal motor neuropathy patients (MMN) (Group 5), thereby differentiating asymmetric forms of CIDP from MMN. These findings suggest that SSEPs may be an important complementary investigation to conventional NCSs in the diagnosis of CADP.     

High-frequency oscillations in the somatosensory evoked potentials of patients with cortical myoclonus: pathophysiologic implications.

SUMMARY: A small series of high-frequency wavelets overlapping the earliest part of the N20 wave (high-frequency oscillations, HFOs) can be observed in the somatosensory evoked potentials (SSEPs) of normal subjects after filtering then with a high-pass filter (>500 Hz). These HFOs have been related to interneuronal activity in the primary somatosensory cortex. In patients with cortical myoclonus there is a sensorimotor cortical hyperexcitability, expressed neurophysiologically as high-amplitude waves in the SSEPs (giant SSEPs). There have been contradicting reports in the literature on the changes in the HFOs in these patients. The authors studied HFOs in a group of 20 patients with cortical myoclonus of different origins and in a control group by means of time-frequency transforms, comparing the results obtained with the amplitude and latency of the classical SSEP waves. All controls had normal HFOs, with two components. Nine patients had no HFOs, nine patients had low-amplitude and/or delayed HFOs, and the remaining two patients, the only without ataxia, had high-amplitude HFOs with a long latency. These results suggest heterogeneity in the pathophysiology of cortical myoclonus, which might be related to the different systems affected.     

Temperature-dependent hysteresis in somatosensory and auditory evoked potentials.

Fourteen adult patients undergoing open heart surgery under induced hypothermia had median nerve, short-latency somatosensory evoked potentials (SSEPs) recorded during cooling (from 36 degrees C to 19 degrees C) and subsequent rewarming. Similar data on another group of patients who had brain-stem auditory evoked potentials (BAEPs) were also analyzed. Hypothermia produced increased latencies of the major SSEP and BAEP components and the latencies returned to normal with subsequent warming. The temperature-latency relationship during the cooling phase was significantly different from that during the warming phase. For SSEP components the temperature-latency relationship was linear during cooling and curvilinear during warming, whereas for BAEP it was curvilinear both during cooling and warming. Furthermore, the regression curves were different during the two phases of temperature manipulation, particularly for temperatures below 30 degrees C both for SSEP and BAEP components. At the onset of warming there was an initial exaggerated warming response on the evoked potential (EP) latencies and amplitude of the EP components. The temperature-latency regression curves were uniformly less steep during the warming phase compared to those during cooling. These findings suggest the existence of hysteresis in the relationship between temperature and EP latencies. The latencies at a given temperature below 30 degrees C depend on whether that temperature is reached during cooling or during warming.     

Re-evaluation of short latency somatosensory evoked potentials (P13, P14 and N18) for brainstem function in children who once suffered from deep coma

One of the major clinical features of brain death is deep coma. Therefore, we re-evaluated retrospectively electrophysiological examinations of brainstem function in about 31 children who had once suffered from deep coma in order to reveal its pathophysiological characteristics. The patient age at coma ranged from 1 month to 10 years (mean 2 years 1 month). The electrophysiological examinations were performed, including any of short-latency somatosensory evoked potential (SSEP), brainstem auditory evoked potential (BAEP) and blink reflexes. We first compared results between the fair and poor prognostic groups, and then re-evaluated SSEP results on a few severely impaired patients with persistent vegetative state (PVS). Subsequently, SSEP clarified more specific findings for a deep coma condition than BAEP and blink reflex. A lack of P14, N18 and N20, and an amplitude reduction or vagueness of P13 in SSEP in these children strongly suggested high risk in their future neurological prognosis. In conclusion, electrophysiological examinations, especially SSEP (P13, P14 and N18), might be very useful in obtaining a long-term neurological prognosis after deep coma in children.     

Anoxic-ischemic encephalopathy

Introduction: Prognostic determination of patients in coma after resuscitation from cardiac arrest is both common and difficult. We explored clinical and electrophysiological testing to determine their associations with favorable and poor outcomes. Methods: We studied 75 comatose patients resuscitated from cardiac arrest, excluding those who were brain dead or continuously sedated; none received hypothermia therapy. Clinical examinations were performed on day 1. Results: The following proportions recovered awareness: 2 of 18 patients with absent pupillary reflexes; 18 of 57 with preserved pupillary reflexes (p=0.08); 2 of 32 with absent corneal reflexes; 16 of 43 with preserved corneal reflexes (p=0.001); 0 of 15 with absent oculovestibular reflexes; and 8 of 29 with preserved oculovestibular reflexes (p<0.037). Purposeful movements were associated with a high probability of recovery, whereas other categories were unfavorable. Other categories of motor response were associated with an increased proportion of those who died without recovering awareness, but each category had some survivors. Somatosensory evoked potentials (SSEPs) were recorded from 47 patients. One of 21 patients with loss of the N20 component survived, compared with survival of 11 of 26 patients in whom it was present (p=0.003). All 5 patients with preserved N70 responses recovered awareness in a subgroup of 33 patients. Sixteen of 22 subjects with mild electroencephalogram (EEG) abnormalities recovered consciousness, compared with the survival of 3 of 50 patients with malignant EEG patterns (p= 0.0000001). Combining SSEP with EEG findings produced even greater predictive value. Conclusion: It seems unlikely that any single test will prove to have 100% predictive value for outcome; further studies combining clinical, EEG, and SSEP testing are warranted.     

Association between somatosensory evoked potentials and EEG in comatose patients after cardiac arrest

ObjectiveTo analyze the association between SSEP results and EEG results in comatose patients after cardiac arrest, including the added value of repeated SSEP measurements.MethodsContinuous EEG was measured in 619 patients during the first 3–5 days after cardiac arrest. SSEPs were recorded daily in the first 55 patients, and on indication in later patients. EEGs were visually classified at 12, 24, 48, and 72 h after cardiac arrest, and at the time of SSEP. Outcome at 6 m was dichotomized as good (Cerebral Performance Category 1–2) or poor (CPC 3–5). SSEP and EEG results were related to outcome. Additionally, SSEP results were related to the EEG patterns at the time of SSEP.ResultsAbsent SSEP responses and suppressed or synchronous EEG on suppressed background ≥24 h after cardiac arrest were invariably associated with poor outcome. SSEP and EEG identified different patients with poor outcome (joint sensitivity 39% at specificity 100%). N20 responses were always preserved in continuous traces at >8 Hz. Absent SSEPs did not re-emerge during the first five days.ConclusionsSSEP and EEG results may diverge after cardiac arrest.SignificanceSSEP and EEG together identify more patients without chance of recovery than one of these alone.     

Neuroanatomic substrates of lower extremity somatosensory evoked potentials.

After stimulation of the lower extremity nerve (tibial nerve), N21 and N23 are recorded from L4 and T12 spine respectively. The far-field potentials of P31 and N35 are registered from Fpz-C5s (fifth cervical spine) or CPi (ipsilateral with respect to the side of stimulation)-ear derivation. Additional far-field potentials of P17 and P24 may be recorded from the scalp when a noncephalic (knee) reference is used. The major positive peak, P40, is registered at the vertex and the CPi. Preceding P40, there is a small negative peak, N37, recorded at the contralateral (CPc) hemisphere. Neuroanatomic substrates of these somatosensory evoked potential (SSEP) components are less well clarified compared with those of upper extremity (median nerve) SSEPs, primarily because clinical application of lower extremity SSEPs is more difficult, and all of the aforementioned potentials but one (P40) are not obligatory components. The concept of "paradoxical lateralization" complicates the issue further. Accumulating evidence, however, suggests that the far-field potentials of P17 and P31 arise from the distal portion of the sacral plexus and brainstem respectively. These correspond to P9 and P14 of the median nerve SSEPs respectively. The spinal potential of N23 is equivalent to the N13 cervical potential of the median nerve SSEP. N35 recorded from the ipsilateral hemisphere is analogous to N18 of the median nerve. Paradoxically lateralized P40 has been thought to represent the positive end of a dipole field, reflected by the negativity at the mesial surface of the contralateral hemisphere, and has commonly been considered to be equivalent to the first cortical potentials (N20) of the median nerve SSEP. However, more recent evidence suggests that the primary positivity is at the mesial cortical surface, and it more likely corresponds to P26 of the median nerve SSEP. Thus the first cortical potential corresponding to N20 is probably a small and inconsistent N37 recorded on the contralateral hemisphere. These assumptions need to be verified further by more extensive clinical studies applied to various neurologic disorders.     

Short-latency somatosensory evoked potentials in brain-dead patients

Ten adult brain-dead patients were evaluated for the presence of clearly defined median nerve short-latency somatosensory evoked potentials (SSEPs). All met clinical criteria recommended by the President's Commission report (1981), had positive apnea tests, and had electrocerebral silent EEGs. P13-P14 and N20 were absent in all scalp-scalp channels, although 3 patients showed P13-P14 in scalp-non-cephalic channels. Of 6 patients showing N13, 3 lacked P13-P14. Our data suggest a characteristic destruction of N20 and rostral P13-P14 generators, with variable rostral-caudal loss of lower generators. SSEPs can provide valuable information about brain-stem activity in the evaluation of suspected brain-dead patients.     

Familial Progressive Myoclonus Epilepsy: Clinical and Electrophysiologic Observations

Summary: Progressive myoclonus epilepsy (PME) is a syndrome complex encompassing different diagnostic entities. Among the 30 cases of PME studied during 1982 and 1992 at the National Institute of Mental Health and Neurosciences, Bangalore, South India, the specific diagnoses included Lafora disease (LD), neuronal ceroid lipofuscinosis (NCL), Unverricht-Lundborg disease (ULD), and myoclonus epilepsy and ragged-red fibres (MERRF).We discuss the familial nature of PME and the clinical and electrophysiological abnormalities in asymptomatic siblings. Eight cases of LD were in three different families with 3 affected siblings in two families (L1, L2) and 2 siblings in the third family (L3). Occipital seizures and behavioral changes occurred in all 3 members of L1 but were absent in the other two families. Age of onset was similar in two families (L1, 11 years; L2, 14.5 years), but not in the third. Presymptomatic EEG abnormalities were observed as long as 6 years before onset in L2. ULD occurred in 2 sisters in one family. Both had identical clinical features and normal somatosensory evoked potentials (SSEPs). The asymptomatic sister of the patient MERRF had abnormal EEG and giant SSEPs for the past 2 years. Thus, although all variations are evident in the overall clinical pattern in each of the PME, affected member of individuals families tend to be similar. Once an index case is identified, electrophysiologic tests (EEG and SSEP) may be useful in identifying other affected siblings in the presymptomatic stage. Key Words: Progressive myoclonus epilepsy–Genetics–Electrophysiology–Presymptomatic.     

Somatosensory evoked potentials of the dog: recording techniques and normal values

Median and tibial nerve somatosensory evoked potentials (SSEPs) of 5 sedated dogs were studied to determine their normal features and optimal stimulation and recording techniques. Cortical potentials were mapped from an extensive array of skull electrodes as each limb was independently stimulated with subdermal needles. The effects of bandpass and stimulus intensity and rate were also assessed. Three cortical components (P1, N1, P2) were evoked by median or tibial nerve stimulation and were localized along the coronal suture at lateral and medial electrodes, respectively. SSEP voltage varied much more than morphology, topography, or latency. The inion was a stable, indifferent reference site. Cortical SSEP frequency content was mostly below 250 Hz. Maximal SSEP voltage was achieved only at stimulus intensities 2-3 times motor threshold. Appropriate methods minimize technical difficulties and consistently yield legible SSEPs.     

Value of multimodal evoked potentials in the assessment of the neurotoxic effects of carbon disulphide

Central nervous system dysfunction among CS2-exposed workers was studied by measuring short latency SSEPs and VEPs. The examinations were done in 40 men. Chronic CS2 intoxication was diagnosed in 21 of them. Latency of N19, N11, N20 of somatosensory evoked potentials and latency of P100 wave of visual evoked potentials were statistically significant longer in CS2 exposed group in comparison with controls. The amplitude of N20 SSEPs was also significantly higher. Increase of N20 amplitude (33 persons) and elongation of its latency (25 persons) were frequent abnormalities of SSEps. In individual assessment of VEPs, most frequent were: abnormal difference in interocular latency of P100 (26 persons) and elongation of P100 latency (25 persons). In the analysed SSEPs and VEPs parameters there was no significant difference between two clinical groups. The authors conclude that the CS2--neurotoxic effect leads to impairment of the peripheral and central part of the somatosensory pathway, as well as to central dysfunction of the visual pathway.     

The N30 component of somatosensory evoked potentials in patients with dystonia.

We recorded short-latency median nerve somatosensory evoked potentials (SEPs) in 10 patients with dystonia (6 with focal dystonia, 3 with generalized dystonia, and 1 with segmental dystonia) and compared them with those of 10 normal controls. The EEG was recorded from 29 sites on the scalp with linked earlobe electrodes for reference. Latencies and amplitudes of P15, postcentral N20 and P45, and frontal N30 were evaluated. The latencies of all potentials were the same in patients and controls. The amplitudes of P15, N20 and P45 were also the same in both groups, but the N30 amplitude of the patients was larger than of the controls. The amplitude of N30 did not vary from the affected side to the unaffected side. Previous work has shown decreased N30 amplitude in patients with Parkinson's disease. Changes in N30 amplitude may be indicative of abnormal excitatory effects on cortex resulting from disorders of the basal ganglia.     

Auditory evoked potentials in anxiety disorder

The pathophysiology of anxiety has received much recent attention. EEG findings in anxiety are nonspecific, and some changes in psychophysiological measures have been reported. We recorded short-latency brainstem auditory evoked potentials (BAEPs) and long-latency auditory event-related potentials (AEPs) in 12 patients with generalized anxiety disorder. All 12 patients had BAEP latencies within clinical norms, but I-V interpeak latencies were significantly longer in patients with anxiety than controls. N1, N2, P2, and P3 AEP components were within normal limits; N1 and P2 were reduced in amplitude in anxiety patients, but differences from controls were not significant. The BAEP findings may suggest altered brain-stem function in anxiety, which has been implied by biochemical studies of anxiety and depression. AEP differences may be related to difficulties in concentration and attention direction reported by anxious patients.     

The use of electrophysiological monitoring in the intraoperative management of intracranial aneurysms

OBJECTIVES: Somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs) have been increasingly utilised during surgery for intracranial aneurysms to identify cerebral ischaemia. Between July 1994 and April 1996, we surgically treated 70 aneurysms in 49 consecutive patients (58 operations) with the aid of intraoperative evoked potential monitoring. This study sought to evaluate the usefulness of SSEP and BAEP monitoring during intracranial aneurysm surgery. METHODS: Mean patient age was 51.9 (range 18-79) years. The sizes of the aneurysms were 3-4 mm (15), 5-9 mm (26), 10-14 mm (11), 15-19 mm (seven), 20-24 mm (six), and >25 mm (five). SSEPs were monitored in 58 procedures (100%) and BAEPs in 15 (26%). The neurological status of the patients was evaluated before and after surgery. RESULTS: Thirteen of the 58 procedures (22%) monitored with SSEPs had SSEP changes (12 transient, one persistent); 45 (78%) had no SSEP changes. Three of 15 patients (20%) monitored with BAEPs had changes (two transient, one persistent); 12 (80%) had no BAEP changes. Of the 14 patients with transient SSEP or BAEP changes, these changes resolved with adjustment or removal of aneurysm clips (nine), elevating MAP (four), or retractor adjustment (one). Mean time from precipitating event to electrophysiological change was 8.9 minutes (range 3-32), and the mean time for recovery of potentials in patients with transient changes was 20.2 minutes (range 3-60). Clinical outcome was excellent in 39 patients, good in five, and poor in three (two patients died), and was largely related to pretreatment grade. CONCLUSIONS: SSEPs and BAEPs are useful in preventing clinical neurological injury during surgery for intracranial aneurysms and in predicting which patients will have unfavourable outcomes.