Recommendations for the clinical use of somatosensory-evoked potentials.

The International Federation of Clinical Neurophysiology (IFCN) is in the process of updating its Recommendations for clinical practice published in 1999. These new recommendations dedicated to somatosensory-evoked potentials (SEPs) update the methodological aspects and general clinical applications of standard SEPs, and introduce new sections dedicated to the anatomical-functional organization of the somatosensory system and to special clinical applications, such as intraoperative monitoring, recordings in the intensive care unit, pain-related evoked potentials, and trigeminal and pudendal SEPs. Standard SEPs have gained an established role in the health system, and the special clinical applications we describe here are drawing increasing interest. However, to prove clinically useful each of them requires a dedicated knowledge, both technical and pathophysiological. In this article we give technical advice, report normative values, and discuss clinical applications.

Visual evoked potentials elicited by circular grating.

In the belief that it would prove a more effective stimulus for eliciting visual evoked potentials, a circular grating was designed so that the relationship between its bar width and visual acuity was held constant, and, therefore, the bars were equally well resolved across the visual field. Visual evoked potentials elicited by the onset presentation of the pattern were evaluated but found to be excessively variable owing to summation of different waveforms generated by equivalent stimulation of different parts of the visual field.

Serial evoked potential studies in patients with definite multiple sclerosis. Clinical relevance.

Twelve patients with clinically definite multiple sclerosis were examined both clinically and electrophysiologically at repeated intervals over one year to determine the clinical relevance of data obtained by serial multimodality evoked potential studies. We frequently found a disparity between the clinical and electrophysiologic changes, and also an excessive variability between test sessions of the responses to stimulation of a clinically involved afferent pathway even when the clinical deficit was stable. Our findings indicate that though evoked potential studies may provide information of diagnostic relevance, their role in monitoring disease progression has not been established.

Brain-stem auditory evoked potentials in children with brain-stem or cerebellar dysfunction.

Brain-stem auditory evoked potentials (BAEPs) were recorded in 23 children who had signs of brain-stem or cerebellar dysfunction. In patients with brain-stem gliomas, BAEPs were abnormal in all except one, in whom involvement of the brain-stem auditory pathway was limited to the midbrain tectum. The BAEPs were normal in neuronal ceroid lipofuscinosis, but abnormal bilaterally in inheritable leukoencephalopathies. All patients with Leigh's encephalopathy had BAEP abnormalities; in two, abnormalities occurred before the appearance of lesions on computed tomographic scan. Patients with Friedreich's ataxia and giant axonal dystrophy had abnormal BAEPs, but the test was normal in a child with similar neurologic findings with vitamin E deficiency. Patients with diffuse metabolic encephalopathies had variable findings. Thus, BAEP abnormalities are nonspecific for various disease processes but are frequently seen in neoplastic and neurodegenerative diseases, with primary white matter or extensive brain-stem involvement.

Sensory perception in Parkinson disease.

OBJECTIVE: To determine whether there is a complex sensory disturbance that may be contributing to the motor deficit in patients with Parkinson disease. DESIGN: Comparison of performance by patients and healthy, age- and sex-matched subjects in tests of various sensory functions. SETTING: The Center for Human Performance and Testing at a university hospital and research center. PARTICIPANTS: Ten subjects with Parkinson disease and 10 control subjects matched for age and sex. MAIN OUTCOME MEASURE: Performance on 4 subjects of the Sensory Integration and Praxis Test: finger identification, graphesthesia, localization of tactile stimuli, and kinesthesia. RESULTS: Data were analyzed using paired t tests for ratio data and the paired Wilcoxon test for ordinal data. Patients with Parkinson disease performed significantly worse (P = .001) than the control patients on the test of kinesthesia. There were no significant differences between the 2 groups on the other subtests. CONCLUSIONS: Without visual guidance, patients with Parkinson disease had more difficulty in perceiving the extent of a movement made to a target away from the body, a task requiring reliance on proprioceptive feedback. Parkinsonian patients had no more difficulty than controls in making movements to a target on the surface of the body when they could use tactile sensations. Movement difficulties in patients with Parkinson disease may relate in part to a decrease in proprioception. Activities that enhance kinesthetic awareness may be an important adjunct to the treatment of these patients.

Effect of pallidotomy on postural control and motor function in Parkinson disease.

OBJECTIVE: To investigate the effects of pallidotomy on postural reactions and other motor parkinsonian deficits. DESIGN: Comparison of performance by patients before and after pallidotomy on tests of balance and function. SETTING: A Parkinson disease Center of Excellence and Center for Human Performance Testing at a university hospital and research center. PARTICIPANTS: Twenty-nine patients with Parkinson disease undergoing pallidotomy. MAIN OUTCOME MEASURES: Performance results on the United Parkinson's Disease Rating Scale (UPDRS), activities of daily living and motor subscales (parts II and III). and posturography (sensory organization test), which were collected before and 3 and 6 months after surgery with patients in the practically defined off state (medication withheld for at least 12 hours). RESULTS: Data were analyzed with a paired Wilcoxon and Spearman correlation. There was a significant improvement in mean +/- SD UPDRS motor subscale score after pallidotomy (before surgery, 52.43+/-13.46; after surgery, 43.93+/-15.15; z= 3.63; P=.003). There were no significant changes in the UPDRS activities of daily living subscale or average stability scores when the group was examined as a whole. However, examination of individual data revealed that 9 (56%) of 16 patients who could stand independently before surgery showed improvement in either the number of falls or the average stability score. No patient who was unable to stand independently before surgery was able to stand independently after it. CONCLUSION: Pallidotomy helped improve overall motor function in patients with parkinsonism and, for some patients, also improved postural stability.

Treatment of unruptured cerebral arteriovenous malformations.

The presence of a cerebral AVM is a potential risk to a patient's life or quality of life. Pharmacologic maneuvers or partial obliteration of an AVM by non-operative means will help most of its nonhemorrhagic manifestations but do not influence the threat of intracranial bleeding, which is the major cause of morbidity and mortality. This risk is eliminated if the AVM is removed. Surgical treatment, however, also carries a risk, and it is therefore important to determine how this risk compares to that of conservative management before surgery is recommended in patients with unruptured AVMs. The present analysis suggests that the surgical mortality and morbidity, although considerably reduced in recent years, still generally precludes surgery for unruptured AVMs. The most favorable figures for surgery are properly applicable to small, superficial AVMs located in clinically silent areas of the brain in young and otherwise well patients who are to be operated upon by surgeons especially experienced in treating AVMs. Even using these favorable figures, however, there is no clear advantage to surgical excision over conservative management over a 20-year period unless AVMs have ruptured once, following which the risks of further episodes of hemorrhage are increased.

The clinical course of spasmodic torticollis.

Among 24 of 36 patients with idiopathic spasmodic torticollis referred to one of us over a 10-year period, who were followed up for more than 1 year, we defined three outcome groups. Three patients (13%) underwent complete or almost complete remission at a median of 3.0 years into the illness. Eight patients (33%) had partial remissions, which tended to occur somewhat later than the first group. The remaining 13 patients had no significant improvement in their disease; they were more likely to be older at the onset of the illness, develop constant rather than intermittent neck deviation, and have a "geste antagonistique." As a whole, the study population was exposed to a wide variety of therapeutic interventions that had little, if any, obvious clinical effect.

Clinical and EEG features of status epilepticus in comatose patients.

We retrospectively evaluated the clinical and EEG features of status epilepticus (SE) in 47 comatose adult patients in whom SE was suspected clinically or because the EEG revealed repetitive electrographic seizures or continuous spike-and-wave activity. Three groups of patients were identified. Group-1 patients (n = 33) had SE both clinically and on EEG. They usually had subtle, clonic movements restricted to the eyes, face, and upper extremities, and the EEG most commonly showed repetitive electrographic seizures or continuous spike-and-wave activity. Group-2 patients (n = 9) also had subtle motor manifestations of seizures, but the EEG was not that of SE, consisting of either irregular slowing with frequent spikes and sharp waves, an irregular mixed-frequency background with episodic accentuation, or diffuse slowing; one patient also had an intermittent burst-suppression pattern. The five patients in Group 3 lacked any clinical signs of seizures, but the EEG showed repetitive electrographic seizures or continuous spike-and-wave activity. There were no significant differences between groups in etiology of SE, response to therapy, or outcome, and there was no obvious relationship between the EEG findings and duration of SE. We conclude that recognition of SE in comatose patients may require both clinical and EEG evaluation since either approach by itself may fail to establish the diagnosis. Furthermore, the EEG findings in established SE do not necessarily progress through the series of defined stages suggested by some authors.

Somatosensory evoked potentials in chronic acquired demyelinating peripheral neuropathy.

We recorded somatosensory evoked potentials (SEPs) over the scalp in eight patients with chronic acquired demyelinating peripheral neuropathy. They were obtained from 15 nerves in which sensory nerve action potentials (SNAPs) were absent or not more than 1 microV, but from which motor responses could be elicited. Motor and sensory (SEP-derived) conduction velocity was determined from the difference in response latency with wrist and elbow stimulation. In 11 nerves, afferent conduction velocity was slowed. In 10, there was relatively equal slowing in sensory and motor axons, whereas in 1 there was disproportionate slowing in afferent fibers. In four nerves, afferent conduction velocity was within the normal range despite slowing of motor conduction. We conclude that SEPs may be useful in evaluating peripheral sensory conduction in the absence of SNAPs, but can provide misleadingly normal data, presumably because of central amplification of an attenuated response arising from a few axons that conduct normally.

Tetrabenazine and movement disorders.

Based on blind review of videotape recordings, we analyzed the ability of tetrabenazine to suppress abnormal movements. The recordings were done before treatment, after 3 weeks on a stable dose (up to 200 mg daily) of tetrabenazine, and then after 3 weeks on placebo. Among the patients who completed the trial, improvement occurred in 6 of 8 with Huntington disease, 6 of 10 with tardive dyskinesia, and 3 of 8 with dystonic disorders. The drug was usually tolerated well.

Electrodiagnostic features of the Guillain-Barré syndrome: the relative sensitivity of different techniques.

We compared the diagnostic sensitivity of somatosensory evoked potentials (SEPs) and F waves with peripheral motor and sensory nerve conduction studies in 15 patients with the Guillain-Barré syndrome. All 4 types of studies were performed on 44 nerves (17 median, 12 ulnar, and 15 lower extremity). In the lower extremities, we used the peroneal nerves for all types of study except peripheral sensory conduction studies, which were performed on the sural nerve. We detected abnormalities by peripheral motor conduction studies in 33 of 44 nerves, by F waves in 31, by SEPs in 23, and by peripheral sensory conduction in 17. The cumulative sensitivity increased with the testing of multiple nerves by motor nerve conduction, sensory nerve conduction, and F-wave studies, but not with multiple SEPs. F-wave studies were significantly more sensitive than SEPs in identifying abnormalities. Thus, the recording of SEPs is indicated for diagnosis of the Guillain-Barré syndrome only if peripheral nerve conduction and F-wave studies are normal.

The Brown-Séquard and S. Weir Mitchell letters.

The two prominent nineteenth-century neurophysiologists/neurologists C.E. Brown-Séquard and S.W. Mitchell maintained an active correspondence during their careers. These letters, never before studied as a unit, provide insight into the men's close collegial association in several domains. They shared camaraderie as pioneer physiologists who tried to bring experimental discoveries from the laboratory to the clinical setting. They critiqued each other's research and facilitated its publication in journals over which they had influence. Through letters of recommendation, they also helped foster each other's local careers. In a period of transition in neuroscience from a traditional anatomic focus to the emerging predominance of neurophysiology and neuropharmacology, their correspondence documents the views of two late nineteenth-century leaders in science and international academic medicine.

Organophosphate polyneuropathy: pathogenesis and prevention.

Organophosphorus-induced delayed polyneuropathy (OPIDP) is initiated by the phosphorylation of a protein neurotoxic esterase (NTE) in the nervous system. A second step, the "aging" of the phosphoryl-enzyme complex, is required to produce the toxic effect. The experimental evidence for this molecular target and the importance of the aging process are reviewed. The catalytic activity of NTE has been used to develop an in vitro screening test that may distinguish the organophosphorus compounds (OPs) that cause neuropathy from those that do not, thereby providing a means for prevention of OPIDP. Moreover, a biochemical screening test, the determination of NTE activity in blood lymphocytes, may predict the development of OPIDP after acute or chronic exposure to OPs, and requires evaluation by carefully designed studies of occupational exposure to OPs.

Clinical and electrodiagnostic features of X-linked recessive bulbospinal neuronopathy.

We describe four men from two kinships affected with X-linked recessive bulbospinal neuronopathy, and one sporadic case. All developed postural tremor, weakness, and fasciculations, with onset from age 25 to 39 years. Weakness began in the pelvic girdle or hands, with dysphagia or dysarthria occurring years later in two. Sensory symptoms were present in only one, who also had diabetes mellitus. In contrast, sural nerve action potentials were small or absent in all. Needle EMG showed widespread chronic partial denervation with reinnervation. The characteristic twitching of the chin produced by pursing of the lips consisted of repetitive or grouped motor unit discharges, rather than fasciculations. Broader awareness of the distinctive features of bulbospinal neuronopathy will probably increase the frequency of its recognition. Diagnosis is important for purposes of providing a prognosis for affected men and genetic counseling for affected families.

Barbiturate anesthesia in the treatment of status epilepticus: clinical experience with 14 patients.

We report our experience using barbiturate anesthesia for the treatment of refractory status epilepticus. Following a retrospective review of eight patients treated with a variety of barbiturates and dosing regimens, we established a specific protocol employing pentobarbital and evaluated it prospectively in six patients. Among the 14 patients, intravenous barbiturates, when administered with a loading dose followed by continuous infusion, were uniformly effective in aborting seizures and producing a burst-suppression EEG pattern. Other than the pupillary light reflex, most patients lost all brainstem reflexes and motor responses during therapy. Barbiturate-induced hypotension was observed in 9 of the 14 patients, and required treatment with pressors in seven cases. Three patients died early as a consequence of their underlying illness, while three others died late for reasons unrelated to the status itself or to anticonvulsant therapy. The time to recovery of function following anesthesia varied highly, spanning hours to days for return of motor function and days to weeks for cognition. Of the eight survivors, four were left with mild cognitive deficits, one returned to his baseline dementia, and three had residual encephalopathies (severe in two). We conclude that barbiturate anesthesia is an extremely effective therapy for refractory seizures. However, its use necessitates recognition of untoward cardiovascular responses and prolonged intensive care.

Visual evoked potentials in the investigation of "blindsight".

We recorded long-latency visual evoked potentials in four patients with homonymous hemianopias, one of whom had clinical evidence of "blindsight." Stimuli consisted of different words that appeared randomly and at a constant angle to either side of the center of a TV screen, and subjects responded to one previously specified word (the "target") by finger extension. Target stimuli in the intact hemifield elicited a well-formed P3 response in all subjects, whereas stimuli in the blind field produced no such response except in the subject with blindsight. In addition, the earlier potentials in this subject were larger with stimulation of the blind hemifield than the intact field. By contrast, a P100 response was present only with stimulation of the intact field in this subject. These results indicate that cognitive processing of visual stimuli can occur even when subjective awareness of such stimuli is absent, and suggest that such processing occurs independently of the geniculostriate pathway.

Botulinum toxin therapy for limb dystonias.

We investigated the effectiveness of botulinum toxin in 17 patients with limb dystonias (10 with occupational cramps, three with idiopathic dystonia unrelated to activity, and two each with post-stroke and parkinsonian dystonia) in a placebo-controlled, blinded study. We identified affected muscles clinically and by recording the EMG from implanted wire electrodes at rest and during performance of tasks that precipitated abnormal postures. There were three injections given with graded doses of toxin (average doses, 5 to 10, 10 to 20, and 20 to 40 units per muscle) and one with placebo, in random order. Subjective improvement occurred after 53% of injections of botulinum toxin, and this was substantial in 24%. Only one patient (7%) improved after placebo injection. Subjective improvement occurred in 82% of patients with at least one dose of toxin, lasting for 1 to 4 months. Response rates were similar between clinical groups. Objective evaluation failed to demonstrate significant improvement following treatment with toxin compared with placebo. The major side effect was transient focal weakness after 53% of injections of toxin.

Expectancy and response strategy to sensory stimuli.

We investigated the relationship between sensory discrimination and the selection of appropriate responses in subjects performing two different reaction-time tasks, in which three auditory stimuli were presented in random order and with a different likelihood of occurrence. Subjects anticipated the need to make different responses based on the likelihood that a particular stimulus would occur on a particular trial. This was determined by the occurrence and distribution of premovement potentials prior to the stimulus, which were consistent with preparation to respond to the most frequently occurring stimulus. These anticipatory cerebral events, however, could be altered after recognition that this frequent stimulus had not occurred. Thus, after the occurrence of a stimulus other than the anticipated frequent tone, the scalp distribution of cerebral potentials changed in a manner suggesting that the next most frequently occurring stimulus was anticipated. Nonetheless, subjects were able to respond to the least probable stimulus both accurately and rapidly despite a failure to anticipate it correctly, as judged by the cerebral "lateralized readiness potential." These results indicate that stimulus evaluation and response selection are integrated and dynamic cerebral processes, and raise doubt about the functional significance of the so-called premovement readiness potential.

The role of thermography in the evaluation of lumbosacral radiculopathy.

We studied 27 normal subjects and 30 patients with low back pain to evaluate the diagnostic accuracy of thermography in the diagnosis of lumbosacral radiculopathy. Thermographic abnormality was defined as the presence of either interside temperature difference exceeding 3 standard deviations from the normal mean, or an abnormal heat pattern overlying the lumbosacral spine. In patients with clinically unequivocal radiculopathy, thermography and electrophysiologic study were similar in diagnostic sensitivity, and the 2 methods agreed on the presence or absence of abnormality in 71% of cases. However, the thermographic findings had limited localizing value. Relative limb warming was often seen in patients with acute denervation on EMG, and limb cooling in those with more chronic lesions, but the side of the root lesion could not be identified confidently by thermography alone. Moreover, thermographic abnormalities appeared not to follow a dermatomal distribution and failed to identify the clinical or electrophysiologic level of radiculopathy in most cases. Thus, the thermographic findings are nonspecific, of little diagnostic value, and of uncertain prognostic relevance.