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Dorsal spinal cord stimulation in the treatment of multiple sclerosis.

Previously published work indicated significant improvement in the symptoms of multiple sclerosis with dorsal spinal cord stimulation. In this study 23 patients with multiple sclerosis documented by history, examination, laboratory studies, and clinical course were treated with dorsal spinal cord stimulation and followed for 19 to 45 months (mean, 32 months). Pre- and postoperative clinical assessment was carried out using the Kurtzke Scale. Walking velocity, upper limb coordination, sphincter function, and sensory function were also evaluated quantitatively. No statistically significant objective improvement in any of these measures was demonstrated. Fifty per cent of the patients initially reported subjective symptomatic improvement, but this declined to 30% at last follow-up. Fifteen of 23 patients experienced complications related mainly to the hardware used and required a total of 21 subsequent operative procedures for correction of these complications. These results do not support the continued clinical use of dorsal spinal cord stimulation in the symptomatic treatment of multiple sclerosis.

Electric Stimulation Therapy

[Axillary brachial plexus block with lidocaine HCl and carbonated lidocaine].

An accordance with the clinical examination recommended by Lanz and Theiss, we studied 26 patients undergoing a blockade of the axillary plexus with lidocaine-CO2 or lidocaine-HCl. Furthermore, we determined the blood concentrations of these local anaesthetics. The study showed no significant differences between the two groups of patients, except that the onset of the blockade was more reliable in one group. There was less impairment of motor function than sensory function. Blood lidocaine concentrations amounted to 2.46 mg/l (mean value) within 25 min. Slight cerebral intoxication could be seen in four patients, with no correlation with possibly high lidocaine concentrations. Lidocaine CO2 is recommended as a rapid blockade of short duration in outpatient regional anesthesia.

Adolescent

Hyperthermia-induced damage to rat sciatic nerve assessed in vivo with functional methods and with electrophysiology.

A 5-mm segment of the rat sciatic nerve was treated in vivo with hyperthermia (43-45 degrees C) for different times using a brass thermode. The effect of this local heat treatment on the nerve was assessed with electrophysiology and using two functional assays. Hyperthermia led to a dose-dependent decrease of motor and sensory function. Electrophysiological examination showed a decrease in amplitude of motor and reflex responses rather than a decrease in conduction velocities. Calculated ED50 values were not significantly different for the two functional and for the electrophysiological methods. Functional recovery from nerve damage took place in all cases. Measured at the same level of damage, i.e., 50% function loss, it took 14 days to recover from complete sensory function loss and 20 days from complete motor function loss. Although both motor and sensory functions were restored, 30 days after hyperthermia no responses could be detected with electrophysiology, this as a result of the thin myelin sheaths that occur upon recovery.

Animals

Capsaicin-sensitive bronchopulmonary receptors with dual sensory-efferent function: mode of action of capsaicin antagonists.

It has been suggested that capsaicin-sensitive interoceptors subserve dual sensory-efferent function in sense of being sites not only for initiating sensory impulses but also for release of mediators. The efferent response of smooth muscle contraction to capsaicin was analyzed in vitro on the trachea and main bronchi of the guinea-pig. Tetrodotoxin-resistant neurogenic contraction of the trachea evoked by capsaicin was inhibited by pretreatment of the tissue with the mast cell depleting agent of compound 48/80. Pretreatment of the preparation with indomethacin or with antagonists of histamine and 5-HT caused no changes in the responses. Electrical field stimulation of the nerve fibres in the main bronchi induced prolonged capsaicin-sensitive bronchoconstriction. Participation of mast cells and particularly leukotrienes in the responses is suggested. Sensory effect and site of action of capsaicin and its antagonists at the pulmonary receptors were tested in vivo by recording the Bezold-Jarisch reflex in the rat. Ruthenium red (0.5-2 mg/kg i.v.) and resiniferatoxin (0.1 micrograms/kg i.v.) did not evoke the vagal reflex triad of bradycardia, fall in blood pressure and apnoea, but antagonized the effect of capsaicin. The cardiorespiratory reflex triad evoked by stimulation of the regenerative region of the receptors by veratridine was not inhibited by ruthenium red. Furthermore, bradycardia evoked by electrical stimulation of the vagal nerve remained unchanged after pretreatment of the rat with either ruthenium red or resiniferatoxin. It is suggested that capsaicin excites the generator region of the receptors. Ruthenium red and resiniferatoxin antagonize its effect at different sites of the capsaicin receptor coupled cation channel.

Animals

Neuroeffector functions of sensory fibres: implications for headache mechanisms and drug actions.

The results of recent investigations designed to elucidate the neuroeffector functions of sensory fibres, the cause of migraine headache and the mechanism of action of antimigraine drugs are reviewed and discussed. Neurogenic inflammation (vasodilatation and neurogenic plasma extravasation) is one explanation for the development of headaches and the blood flow changes which occur during migraine headache. Numerous studies have recently been carried out on rats and guinea-pigs into the effects of antimigraine agents, including ergot alkaloids, sumatriptan and non-steroidal anti-inflammatory drugs (NSAIDs), on neurogenic plasma protein extravasation in the dura mater induced by electrical stimulation of trigeminal ganglia or systemic administration of capsaicin. It is known that the dura mater is able to produce headaches in man. Ergot alkaloids have been shown to block neurogenic inflammation via a C-fibre dependent neuronal mechanism. Sumatriptan appears to act fairly similarly although, whereas the ergot alkaloids are non-selective for either 5-hydroxytryptamine (5-HT; serotonin) receptors or 5-HT1, sumatriptan is selective for 5-HT1 receptors. The antimigraine action of NSAIDs may be via either an effect on blood vessels or an effect on the nerve fibre. The antimigraine effects of ergot alkaloids, sumatriptan and NSAIDs are discussed in the light of the common vasoconstrictor actions of these agents and knowledge that vasodilatation is apparently not responsible for migraine headache pain in most cases.

Animals

Introduction to the symposium on functional amblyopia: sensory or motor disorder?

The theme of the symposium is identified by 2 questions: (1) is the mechanism that underlies functional amblyopia sensory or motor? and (2) How do sensory and motor factors contribute to the loss of acuity in amblyopic eyes? The answers to these questions as well as to several questions about clinical diagnosis and treatment of amblyopia are provided in the following 7 papers and panel discussion that comprise this symposium.

Amblyopia

Impairment and recovery profiles of sensory-motor function following stroke: single-case graphical analysis techniques.

Graphical analysis procedures have been developed to improve interpretation of sensory-motor tests from individual subjects following acute brain damage. The procedures have been applied to 11 unilateral stroke patients assessed serially over 12 months on a computerized quantitative sensory-motor test battery of which grip strength, arm speed, and tracking have been chosen for illustrative purposes. The results indicate that four graphs are necessary to fully demonstrate neurologic impairment and recovery of each sensory-motor function, although fewer graphs would be satisfactory in some applications. Such analyses have proven valuable in the display of serial performance of individual patients but demonstration of impairment and recovery is much more difficult than for group analyses.

Activities of Daily Living

Heart rate development and sensory-evoked cardiac responses in perinatal rats.

Sensory-evoked changes in heart rate (HR) are often used to assess sensory function in infants, but HR measures have not been applied in studies of perinatal sensory function. Normative HR data are needed to judge whether baseline characteristics and response properties of the late fetal and newborn heart are appropriate as a dependent measure in sensory studies. We compared parameters of HR development and phasic cardiac responses to stimulation across the perinatal period in Norway rats. EKG was measured in cesarean-delivered prenatal rats (embryonic day 20-day of birth; conception = E0) and compared to both cesarean and vaginally delivered neonates (day of birth-postnatal day 2; birth = P0). Resting heart rate increased monotonically across the perinatal period, except between E21 and DOB (Experiment 1). During an hour-long test, HR was strong and stable. Variations in HR across successive measurement intervals (10 sec) were uniformly low (less than 2%) in all age groups. In Experiment 2, fetuses and neonates responded with dramatic HR decelerations (20-80 bpm) to an intraoral infusion of lemon extract. HR responses did not appear to be reflexively mediated by changes in respiration. These findings suggest that parameters of resting HR and cardiac responses to stimulation are well suited to studies of perinatal sensory function.

Animals

Effects of hemodialysis on the cognitive and sensory-motor functioning of the adult chronic hemodialysis patient.

Twenty chronically dialyzed adults were administered a repeatable battery of 14 cognitive and sensory-motor tests on 3 consecutive days: immediately prior to their midweek dialysis, approximately 20 hr after their midweek dialysis, and again immediately prior to their end-of-the week dialysis. Serum electrolyte and methylamine analyses were performed at each test session. When compared to established norms, these patients scored within the normal range in a wide variety of areas. Limited impairments, probably due to peripheral neuropathy, were in evidence on the Grooved Pegboard, Finger Tapping (females), and Grip Strength (females) measures. Impairments suggestive of cerebral dysfunction were also noted on the Benton Visual Retention Test and on the Trail Making Test, Parts A and B, with particularly severe impairment noted on Part B. Despite significant daily changes in serum levels of toxic substances retained in uremia, there was little or no evidence to suggest that well-dialyzed patients undergo daily fluctuations in their cognitive and sensory-motor functioning.

Adult

Correlation between sensory loss, functional disability and short-latency somatosensory evoked potentials in strokes.

Short-latency somatosensory evoked potentials (SEPs) were reviewed for their correlation with the clinical features and functional deficit of 64 patients with supratentorial deep or superficial ischemic strokes. Abnormal SEPs correlated with lesions of proprioceptive pathways and with clinical sensory impairment. 87% of patients with abnormal SEPs had sensory loss and 88% of those with normal SEPs had normal sensation. The reliability of the SEPs made them useful in an objective demonstration of an abnormality in sensory system function. However, they are not sensitive enough to be used as a method of prognostication because 1) the SEPs abnormalities depend on the involvement of their generators and therefore may be normal in some thalamic or cortical lesions associated with severe disability, 2) 48.4% of the patients studied had normal sensation, and 3) in the group with absent SEPs, the functional disability was poorer than in the group with normal SEPs, not in relation to the type of the sensory loss but to the volume and location of the infarcted area.

Activities of Daily Living

State of health and its association with death among old people at three-years follow-up. I. Lung function, circulation, sensory and motor apparatus.

A general medical examination was performed of 569 Copenhagen inhabitants aged 75, 80, and 85 years in the participants' own homes as part of an epidemiological, sociomedical intervention study. The present report contains the results of this examination regarding lung function, circulation, sensory, and motor apparatus. Curves are presented expressing the normal peak expiratory flow rate (PEFR) for men and women 75-85 years old. More men than women had a compromised lung function. Regarding circulation and motor apparatus, more women and 85-year-olds showed impairments. Functional vision and hearing declined with age, but no significant differences could be demonstrated between men and women, although a preponderance of women tended to show hearing disability. Institutionalised participants were more inclined to have impairment of lung function and sight and to walk with difficult. Gait disturbances and impairment of vision were the objective health measurements most strongly related to death at follow-up after three years.

Aged

Steady-state evoked potentials.

The advantages of steady-state EP recording include (1) speed in assessing sensory function in normal and sick infants (e.g., in amblyopia) and in sick adults (e.g., in multiple sclerosis); (2) monitoring certain activities of sensory pathways that do not intrude into conscious perception; (3) rapidly assessing sensory function when a large number of subjects must be tested (e.g., in refraction); (4) objective measurement at very high suprathreshold levels where psychophysical methods are difficult or ineffective; (5) rapidly assessing sensory function in normal subjects when EP variability and nonstationarity preculde lengthy experiments; and (6) proving a speedy objective equivalent to behavioral test in animals.

Adult

Somatosensory evoked potentials for orthopaedic spine trauma.

Monitoring somatosensory evoked potentials (SSEPs) for intraoperative assessment of spinal cord activity provides a reliable and valid measure of sensory function during manipulation of structures placing cord function at risk. We describe a multichannel technique with artifact reductions that has proved successful in 415 spine cases including 146 posttraumatic injuries. Accurate prediction of sensory function in near or at 100% of cases is possible. No patient has recovered with less than the predicted sensory function. Statistics and cases are presented. A professional-level consultant role for SSEP monitoring is suggested as necessary for valid use of the technique.

Adult

Bootstrap variance estimators for the parameters of small-sample sensory-performance functions.

The bootstrap method, due to Bradley Efron, is a powerful, general method for estimating a variance or standard deviation by repeatedly resampling the given set of experimental data. The method is applied here to the problem of estimating the standard deviation of the estimated midpoint and spread of a sensory-performance function based on data sets comprising 15-25 trials. The performance of the bootstrap estimator was assessed in Monte Carlo studies against another general estimator obtained by the classical "combination-of-observations" or incremental method. The bootstrap method proved clearly superior to the incremental method, yielding much smaller percentage biases and much greater efficiencies. Its use in the analysis of sensory-performance data may be particularly appropriate when traditional asymptotic procedures, including the probit-transformation approach, become unreliable.

Animals

Measurement of integrated sensory-motor function following brain damage by a computerized preview tracking task.

A preview tracking task has been developed which has particular application to neurological assessment and rehabilitation. Generated and monitored by a graphic display computer, it permits accurate global quantification of the upper-limb sensory-motor system. The incorporation of 'preview' into the tracking task is considered to significantly increase its effectiveness and relevance in relation to normal daily activities. Applied to three groups of normal subjects, several features of normal psychomotor performance and learning were identified or verified: hand dominance is not significant in overall arm control; learning does not completely plateau; increase in age (15-59 years) results in only a minor overall decrement in performance; an initial wide performance distribution decreases dramatically in subsequent sessions. Applied to brain-damaged patients, particularly head injury or stroke, the preview tracking task allows assessment at regular intervals enabling sensory-motor recovery curves to be generated. The potential of this technique, to help determine the efficacy of therapeutic procedures on the recovery process, is illustrated with the presentation of results from three brain-damaged patients demonstrating zero, significant and disjointed recovery of sensory-motor function. The usefulness of the preview tracking task can be expanded by combination with a less frequently applied but more component specific neurological assessment battery.

Adolescent

Mechanisms of depletion of substance P by capsaicin.

Capsaicin is a neurotoxin that can deplete sensory nerves of their content of substance P and interfere with certain sensory functions, such as responses of animals to noxious heat stimuli. In adult guinea pigs, a species that is susceptible to the effects of capsaicin on both substance P content and sensory function, capsaicin induces selective depletion of substance P from dorsal root ganglia and the dorsal spinal cord, sites of the cell bodies and central terminals of primary afferent neurons, respectively. As the onset of thermal analgesia in guinea pigs precedes depletion of substance P, direct neural actions of capsaicin probably account for its effects on sensory function. Capsaicin interferes with the retrograde transport of nerve growth factor (NGF) to the cell bodies of sensory nerves. Decreased availability of NGF at the site of neural protein synthesis leads to decreased synthesis of substance P. After failure of synthesis of substance P, the content of the peptide in sensory nerves gradually decreases until depletion occurs.

Analgesia

Requirement of the cheB function for sensory adaptation in Escherichia coli.

The chemotactic behavior of Escherichia coli mutants defective in cheB function, which is required to remove methyl esters from methyl-accepting chemotaxis proteins, was investigated by subjecting swimming or antibody-tethered cells to various attractant chemicals. Two cheB point mutants, one missense and one nonsense, exhibited stimulus response times much longer than did the wild type, but they eventually returned to the prestimulus swimming pattern, indicating that they were not completely defective in sensory adaptation. In contrast, strains deleted for the cheB function showed no evidence of adaptation ability after stimulation. The crucial difference between these strains appeared to be the residual level of cheB-dependent methylesterase activity they contained. Both point mutants showed detectable levels of methanol evolution due to turnover of methyl groups on methyl-accepting chemotaxis protein molecules, whereas the cheB deletion mutant did not. In addition, it was possible to incorporate the methyl label into the methyl-accepting chemotaxis proteins of the point mutants but not into those of the cheB deletion strain. These findings indicate that cheB function is essential for sensory adaptation in Escherichia coli.

Adaptation, Physiological

The correlation between sensory-efferent functions mediated by the capsaicin-sensitive neurons and substance P content of the rat urinary bladder.

The substance P-like immunoreactivity (SP-LI) of the urinary bladder of adult rats was depleted by capsaicin desensitization (50 mg/kg, s.c., 4 days before) or extrinsic denervation (pelvic ganglionectomy) thus indicating its neurogenic sensory origin. SP-LI levels were inversely proportional to the volume threshold for micturition but not to the amplitude of micturition contraction. Moreover SP-LI levels were directly related to the amplitude of the capsaicin- but not field stimulation-induced contraction of the rat isolated bladder. These findings indicate that the SP-LI level of the rat bladder is a useful index for monitoring the dual sensory-efferent functions of the capsaicin-sensitive innervation of this organ.

Animals