Quantitative assessment of cerebral connectivity deficiency and cognitive impairment in children with prenatal alcohol exposure.

It is common knowledge that alcohol consumption during pregnancy would cause cognitive impairment in children. However, recent works suggested that the risk of drinking during pregnancy may have been exaggerated. It is critical to determine whether and up to which amount the consumption of alcohol will affect the cognitive development of children. We evaluate time-varying functional connectivity using magnetoencephalogram data from somatosensory evoked response experiments for 19 teenage subjects with prenatal alcohol exposure and 21 healthy control teenage subjects using a new time-varying connectivity approach, combining renormalised partial directed coherence with state space modeling. Children exposed to alcohol prenatally are at risk of developing a Fetal Alcohol Spectrum Disorder (FASD) characterized by cerebral connectivity deficiency and impaired cognitive abilities. Through a comparison study of teenage subjects exposed to alcohol prenatally with healthy control subjects, we establish that the inter-hemispheric connectivity is deficient for the former, which may lead to disruption in the cortical inter-hemispheric connectivity and deficits in higher order cognitive functions as measured by an IQ test, for example. We provide quantitative evidence that the disruption is correlated with cognitive deficits. These findings could lead to a novel, highly sensitive biomarker for FASD and support a recommendation of no safe amount of alcohol consumption during pregnancy.

Botulinum toxin A for palmar hyperhidrosis: assessment with sympathetic skin responses evoked by train of stimuli.

Objective assessment of the effect of botulinum toxin A (BT) treatment in primary palmar hyperhidrosis (PH) is attempted by different methods. We decided to use for this purpose sympathetic skin responses evoked by train of stimuli (TSSR). Twenty patients with severe PH (five female, median age 24, range 18-36) were examined regularly over 3 months after receiving 50 UI BT in each palm. TSSR were recorded from the palms after sensory stimulation by a train of three supramaximal electric pulses 3 millisecond apart. Results were compared to longitudinally studied TSSR of 20 healthy sex- and age-matched control subjects. All hyperhidrosis patients reported excellent improvement. TSSR amplitudes decreased at week 1 (mean 54% range 48%-67%) and over the following months in a clinically significant trend (slope R=-.82, P<.0001). TSSR in controls changed insignificantly (±13% from the baseline). The difference between patients and controls was highly significant at any time point (P<.001). This study suggests that TSSR may help in assessment of treatments in PH. It confirms objectively the efficacy of BT in PH.

Neurophysiological assessment of auditory, peripheral nerve, somatosensory, and visual system functions after developmental exposure to ethanol vapors.

Ethanol-blended gasoline entered the market in response to demand for domestic renewable energy sources, and may result in increased inhalation of ethanol vapors in combination with other volatile gasoline constituents. It is important to understand potential risks of inhalation of ethanol vapors by themselves, and also as a baseline for evaluating the risks of ethanol combined with a complex mixture of hydrocarbon vapors. Because sensory dysfunction has been reported after developmental exposure to ethanol, we evaluated the effects of developmental exposure to ethanol vapors on neurophysiological measures of sensory function as a component of a larger project evaluating developmental ethanol toxicity. Pregnant Long-Evans rats were exposed to target concentrations 0, 5000, 10,000, or 21,000 ppm ethanol vapors for 6.5h/day over GD9-GD20. Sensory evaluations of male offspring began between PND106 and PND128. Peripheral nerve function (compound action potentials, nerve conduction velocity (NCV)), somatosensory (cortical and cerebellar evoked potentials), auditory (brainstem auditory evoked responses), and visual evoked responses were assessed. Visual function assessment included pattern elicited visual evoked potentials (VEPs), VEP contrast sensitivity, and electroretinograms recorded from dark-adapted (scotopic), light-adapted (photopic) flashes, and UV flicker and green flicker. No consistent concentration-related changes were observed for any of the physiological measures. The results show that gestational exposure to ethanol vapor did not result in detectable changes in peripheral nerve, somatosensory, auditory, or visual function when the offspring were assessed as adults.

Neurophysiological assessment of the sedative and analgesic effects of a constant rate infusion of dexmedetomidine in the dog.

The sedative and analgesic effects of continuous rate infusion (CRI) of dexmedetomidine (DEX) were investigated in Beagle dogs (n=8) using auditory and somatosensory evoked potentials (AEPs and SEPs) recorded before, during and after a CRI of saline or DEX (1.0, 3.0, 5.0 µg/kg bolus, followed by 1.0, 3.0, 5.0 µg/kg/h CRI, respectively). The results showed a significant reduction in AEP at doses of 1.0 µg/kg/h and above and a significant reduction of the SEP at doses of 3.0 and 5.0 µg/kg/h. Neither the AEP nor the SEP was further reduced at 5.0 µg/kg/h when compared to 3.0 µg/kg/h, although a slower return towards baseline values was observed at 5.0 µg/kg/h. The mean plasma levels (±SEM) of DEX during infusion were 0.533±0.053 ng/mL for the 1.0 µg/kg/h dose, 1.869±0.063 ng/mL for the 3.0 µg/kg/h dose and 4.017±0.385 for the 5.0 µg/kg/dose. It was concluded that in adult dogs, a CRI of DEX had a sedative and analgesic effect that could be described quantitatively using neurophysiological parameters. Sedation was achieved at lower plasma levels than required for analgesia, and DEX had a longer (but not larger) effect with infusion rates above 3.0 µg/kg/h.

Epidural analgesia after scoliosis surgery: electrophysiologic and clinical assessment of the effects of bupivacaine 0.125% plus morphine versus ropivacaine 0.2% plus morphine.

STUDY OBJECTIVE: To study the electrophysiologic and clinical effects of epidural morphine combined with either bupivacaine 0.125% or ropivacaine 0.2%. DESIGN: Comparative, randomized, double-blind study. SETTINGS: Intensive care unit and hospital ward of a university hospital. PATIENTS: 18 adult ASA physical status I and II patients with degenerative or idiopathic scoliosis, undergoing posterior spinal fusion with instrumentation. INTERVENTIONS: Patients received epidural administration of 10-mL bolus of either bupivacaine or ropivacaine followed by a 6-mL/h infusion for 48 hours of unlabeled local anesthetic. In all patients, epidural morphine 5 mg was added daily. MEASUREMENTS: Assessment was focused mainly on somatosensory cortical evoked potentials, soleus H-reflex, and F waves. These electrophysiologic data were recorded before and after epidural medications. Second, respiratory rate, Paco(2), visual analog score (VAS), and side effects such as postoperative nausea and vomiting (PONV), gastrointestinal (GI) transit delay, and urinary retention were noted. MAIN RESULTS: Bupivacaine 0.125% + morphine was given to 9 patients, and ropivacaine 0.2% + morphine was given to 9 other patients. H-reflex, F waves, and somatosensory cortical evoked potential recording remained unchanged across the time of assessment. Respiratory rate and Paco(2) values were normal. VASs were indifferently low at rest, but they were lower with bupivacaine than with ropivacaine on mobilization. The frequency of PONV was indifferently high. No altered GI transit or urinary retention was noted. CONCLUSION: After epidural administration during the study conditions, bupivacaine 0.125% and ropivacaine 0.2% combined with morphine allow for neurologic examination.

Cortical somatosensory evoked potentials and spasticity assessment after botulinum toxin type A injection in children with cerebral palsy.

PURPOSE: The mechanism of Botulinum Toxin Type A (BTX-A) action at the neuromuscular junction is well known. But from the introduction of BTX-A, some authors have suggested a central action of BTX-A and possible side effects far from the site of injection. Some studies demonstrate an improvement of cortical SEPs associated with reduction of spasticity after BTX-A injection. The aim of the present study was to determine the effect of BTX-A treatment on cortical somatosensory potentials (SEP). MATERIAL AND METHODS: A group of twenty nine children ranging from 2 to 17 years old with cerebral palsy were studied. Each patients spasticity level was evaluated before, 2 weeks and 6 weeks after BTX-A injection by the Modified Ashworth Scale and modified Gait Physician's Rating Scale. The SEPs from lower and upper extremities were performed before and between 2 and 6 weeks (19.34 +/- 8.82 days) after BTX-A administration. RESULTS: The mean spasitity level was significantly lower 2 and 6 weeks after BTX-A injection. The gait analysis by modified Physician's Rating Scale (PRS) showed significant improvement two weeks and six weeks after BTX-A injection. SEPs results were abnormal before BTX-A injection in 25 children with cerebral palsy. However we didn't find any significant changes of SEPs latencies after BTX-A injection. CONCLUSIONS: The results of SEP after BTX-A administration in children with cerebral palsy do not confirm the central action of BTX-A on somatosensory pathways. We did not find any significant changes of SEP latencies associated with clinical reduction of spasticity. It seems that SEP results could support the opinion, that BTX-A does not have any direct central effect on sensory pathways. Remote side effects may be explained by an indirect mechanism due to modification of the central loops of reflexes or to hematogenous spread of BTX-A.

Somatosensory evoked potentials as an objective assessment of the sensory median nerve blockade after infraclavicular block.

PURPOSE: Median nerve somatosensory evoked responses (MnSSER) alterations were compared to clinical tests (cold and pinprick) variations, in 20 ASA I adult patients following infraclavicular block obtained with 40 mL ropivacaine 0.5% to assess first, the difference of time course of the respective electrophysiological and clinical signs, and second, the objectivity and the reproducibility of MnSSER changes. CLINICAL FEATURES: Four MnSSER derivations (Erb's point; cutaneous projection of peripheral end of brachial plexus; posterior neck at C6 level, frontal and controlateral parietal scalp) were monitored and recorded for retrospective analysis. Continuous data acquisition were started before ropivacaine injection (baseline) and maintained for 30 min thereafter. Every three minutes after ropivacaine injection, cold and pinprick tests were performed in the hand median nerve cutaneous supply zone and were assessed using a sensory visual score (varying from 0-10). Data were compared using analysis of variance. Although MnSSER values were stable during baseline period, after ropivacaine administration, severe progressive amplitude depressions of selected MnSSER were detected in every patient. While clinical cold and pinprick tests became positive (score > 8) only 15.8 +/- 1.2 min and 20.1 +/- 1.8 min respectively after ropivacaine administration, the mean time to observe the earliest MnSSER 20% amplitude decrease at Erb's point derivation was reduced to 5.6 +/- 1.1 min (P < 0.01). CONCLUSION: Selected MnSSER amplitude reduction indicates objectively the onset of median nerve anesthesia following infraclavicular brachial plexus block before the appearance of clinical signs.

Anesthesia for intraoperative neurophysiologic monitoring of the spinal cord.

Intraoperative neurophysiologic monitoring (INM) using somatosensory and motor evoked potentials (MEPs) has become popular to reduce neural risk and to improve intraoperative surgical decision making. Intraoperative neurophysiologic monitoring is affected by the choice and management of the anesthetic agents chosen. Because inhalational and intravenous anesthetic agents have effects on neural synaptic and axonal functional activities, the anesthetic effect on any given response will depend on the pathway affected and the mechanism of action of the anesthetic agent (i.e., direct inhibition or indirect effects based on changes in the balance of inhibitory or excitatory inputs). In general, responses that are more highly dependent on synaptic function will have more marked reductions in amplitude and increases in latency as a result of the synaptic effects of inhalational anesthetic agents and similar effects at higher doses of intravenous agents. Hence, recording cortical somatosensory evoked potentials and myogenic MEPs requires critical anesthetic choices for INM. The management of the physiologic milieu is also important as central nervous system blood flow, intracranial pressure, blood rheology, temperature, and arterial carbon dioxide partial pressure produce alterations in the responses consistent with the support of neural functioning. Finally, the management of pharmacologic neuromuscular blockade is critical to myogenic MEP recording in which some blockade may be desirable for surgery but excessive blockade may eliminate responses. A close working relationship of the monitoring team, the anesthesiologist, and the surgeon is key to the successful conduct and interpretation of INM.

Assessment of analgesia in man: tramadol controlled release formula vs. tramadol standard formulation.

OBJECTIVE: The present study tested analgesia produced by a new controlled release formulation of tramadol. The investigation employed an experimental pain model based on chemo-somatosensory event-related potentials (CSSERP) in response to painful chemical stimuli applied to the nasal mucosa. STUDY: Twenty healthy volunteers participated in the experiments, which followed a controlled, randomised, double-blind, 3-way cross-over design. Each of the three medications (tramadol 100 mg [T100], tramadol controlled release 100 mg [TCR100] and tramadol controlled release 150 mg [TCR150]) was administered orally to fasting subjects. There was at least a 6 day washout period between tests. Each experiment was divided into five sessions, which took place before and 2, 4, 6, and 12 h after drug administration. In addition to the assessment of CSSERP, subjects rated the intensity of both the tonic and phasic painful stimuli. Nonspecific drug effects were also monitored by means of frequency analysis of the spontaneous EEG, ratings of adverse effects, and the subjects' performance in a tracking task. RESULTS: The significant reduction of amplitude N1 at central recording positions indicated that TCR 150 was the most effective analgesic 12 h after administration. Both 6 and 12 h after administration TCR 100 was more effective in terms of analgesia compared to T100. In addition, TCR100 appeared to produce fewer adverse effects than the standard formulation of tramadol. CONCLUSIONS: The controlled release formulation can be expected to become a valuable tool in peroral therapeutic regimens for chronic pain.

Effect of anesthetic variables on dermatomal somatosensory-evoked potential monitoring in elective lumbar spinal surgery.

We studied 108 adult cases of elective lumbar surgery using dermatomal somatosensory-evoked potential (DSEP) monitoring to evaluate its usefulness due to concern over potential neurologic injury during pedicle screw insertion. Both surgeons used all of the necessary precautions required during surgery so that DSEP monitoring was not the "primary," but rather a backup system for operative security. Quality tracings were obtained in 71% of cases; anesthetic difficulties being the major cause of poor monitoring. There were no neurological complications related to pedicle screw insertion. We found that DSEP monitoring was an excellent method to verify intraoperative neurological status, but required a high degree of cooperation between the anesthesiologists, monitoring technician, and surgeons. In today's cost-containment environment, its usefulness is subjected to the expertise of the spine surgeon and the hospital setting.

Assessment of corticospinal and somatosensory conduction simultaneously during scoliosis surgery.

The function of descending motor pathways and that of ascending sensory pathways in the spinal cord were monitored at the same time in 120 patients undergoing surgery for scoliosis. Transcranial electrical stimulation of the motor cortex was performed simultaneously with stimulation of the tibial nerves in the popliteal fossae, and the descending and ascending volleys were recorded from the spinal cord at two levels using epidural electrodes. Stable recordings of both volleys have been obtained in all neurologically normal patients and in many with pre-existing neurological deficits. The experimental conditions which resulted in reliable recordings were explored in select patients and include: a vertex-anode/lateral cathode montage for transcranial stimulation, epidural recording of evoked corticospinal and somatosensory volleys at two spinal levels, a high-pass filter of 500 Hz, and stable anaesthesia. The epidural recording allows full muscle relaxation and the use of volatile anaesthetics; recording at two levels allows a deterioration in function to be identified quickly and distinguished from an artifactual change.

Reliability of quantal parameter estimates and their changes during long-term potentiation in guinea pig hippocampal slices.

Previously we found increases in quantal content (m) and smaller increases in quantal size (v) during long-term potentiation (LTP) in CA1 of hippocampal slices. However, the validity of the deconvolution technique was questioned recently because v estimates correlated with the noise standard deviation (Sn). In computer simulations we show a double-step dependence of v on Sn/v: correct v estimates (within +/- 20%) for Sn/v < or = 0.5 and overestimates (correlated with Sn) for Sn/v > 0.5. A novel 'noise addition' procedure is proposed for accepting reliable solutions on the basis of the double-step relationship between v and Sn. Quantal analysis of LTP for more reliable solutions confirmed previous conclusions.

Quantitative assessment of extradural bupivacaine analgesia.

Bupivacaine (0.5%) 20 ml was administered extradurally to six healthy volunteers. It was found that simultaneous application of 10 needles to the skin could evoke pain when analgesia was obtained to one needle stimulation. In addition, a laser beam was used as a quantitative technique to activate simultaneously many cutaneous nociceptors. For 7 h, thresholds (sensory and pain) and pain-evoked brain potentials (amplitude and latency) to laser stimulation were monitored and used for quantitative assessment of onset, efficacy and duration of analgesia at various dermatomes (C7, T8, T10, T12, L1, L3, S1). The onset time of analgesia was shortest and conduction delay longest at the dermatome related to the site of injection (L3). Full analgesia was obtained at L1, L3 and S1, although the peak efficacy at S1 was delayed for 120-180 min after injection. A minor effect was found at dermatome C7 approximately 60 min after injection.

Evoked potentials in assessment and follow-up of patients with Wilson's disease.

Treatment of 9 patients with Wilson's disease was prospectively studied with evoked potentials and magnetic resonance imaging (MRI). Oral penicillamine therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP) conduction times in 6 and 4 neurologically symptomatic patients, respectively. ABP and SEP were normal in 3 other symptom-free patients. MRI showed cerebral lesions in 4 of 7 patients. Quantified indices of brain atrophy were unaffected by treatment. ABP and SEP may reveal a reversible component of the disease that cannot be detected by MRI, and may be a more sensitive measure of treatment efficacy.

[Assessment of the effectiveness of analgesics in the pain laboratory]. / Zum Nachweis der Wirksamkeit von Analgetika im Schmerzlabor.

In 1987 the Fifth World Congress on Pain was held in Hamburg with about 2,500 participants, for the first time in Germany after the previous congresses in Florence, Montreal, Edinburgh and Seattle. --In the following lines, Professor Bromm, one of the organisers of the congress, gives a brief insight into modern methods to measure the efficacy of analgesics.

Neurological and electroneuromyographic assessment of the adverse effects of acrylamide on occupationally exposed workers.

Seventy-one acrylamide workers and fifty-one unexposed referents were studied. Weak legs and numb hands and feet, preceded by skin peeling from the hands, were the early symptoms of the acrylamide workers; their early signs were impairment of vibration sensation in their toes and loss of ankle reflexes. Three cases had cerebellar involvement followed by polyneuropathy due to heavy exposure. Electroneuromyographic changes, including a decrease in the sensory action potential amplitude, neurogenic abnormalities in electromyography, and prolongation of the ankle tendon reflex latency, are of greater importance in the early detection of acrylamide neurotoxicity since they can precede the neuropathic symptoms and signs. The diagnostic criteria for occupational acrylamide intoxication of this study revealed three severe poisonings, six moderate poisonings, and 43 mild poisonings. The total prevalence of acrylamide poisoning was 73.2%. The prevention of dermal exposure to acrylamide should be emphasized.

[Value of early acoustic and somatosensory evoked potentials in monitoring and prognostic assessment of coma in barbiturate therapy--comparison with clinical aspects and EEG]. / Zum Stellenwert früher akustischer und somatosensorisch evozierter Potentiale in der Uberwachung und prognostischen Beurteilung des Komas unter Barbiturattherapie--vergleichende Untersuchungen mit Klinik und EEG.

25 comatose patients suffering from severe cerebral lesions of different etiology were examined during barbiturate-therapy by Glasgow-Pittsburg-Coma-Scoring-System (GPCS), EEG, somatosensory and brainstem acoustic evoked potentials. The findings were correlated in view of prognostic prediction and importance for monitoring. A modified form of the Glasgow-Outcome-Score (GOS; independent-survival, dependent-survival, dead) was used for evaluating the outcome. In case of an initial GPCS less than 10 points none of the patients survived, in case of GPCS greater than 10 points 11 out of 19 patients survived. The latter relation of survival was also found in patients with improving or impairing scores during the observation period. In case of initial burst-suppression pattern in the EEG 7 out of 11 patients survived, in case of diffuse abnormalities with or with-out additional focal signs - 4 out of 10 patients survived, but in the latter there was none with an outcome of independent survival. All patients with an isoelectric EEG died. In case of bilateral recording of scalp- SEP 7 out of 11 patients survived, in case of unilateral loss of scalp-EP 4 out of 8 patients survived, but in the latter cases none with an outcome of independence. All patients with initial bilateral failure of scalp-SSEP or loss during the observation period died. In case of bilateral registrable BAEP (wave I to V) 11 out of 17 patients survived. All patients with initial uni- or bilateral failure of those potentials or loss during the observation period died.(ABSTRACT TRUNCATED AT 250 WORDS)