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Intravenous infusion of 4-AP in chronic spinal cord injured subjects.

STUDY DESIGN: A prospective double blind cross over trial of intravenous 4-Aminopyridine (4-AP). OBJECTIVE: To determine the efficacy of this drug in the treatment of spinal cord injured (SCI) patients for neurologic impairment, pain and spasticity. SETTING: The post anesthesia care unit (PACU) of a tertiary care acute hospital. METHODS: Twelve paraplegic patients were enrolled in a double blind cross over intravenous trial of 4-Aminopyridine (4-AP). Thirty milligrams of 4-AP or placebo were administered over a 2 h period. Patients were serially examined during and after the infusion clinically for pain, sensorimotor function, hypertonicity and motor control using electromyography (EMG). Samples of blood and cerebrospinal fluid (CSF) were also analyzed at similar intervals. RESULTS: Despite penetration of 4-AP into the CSF, no significant differences were noted in the clinical and EMG parameters at the times measured. Individual changes in sensory function were reported by some patients in both the placebo and 4-AP trials, however mean values were not robust. Frequently, patients complained of unpleasant symptoms during the 4-AP infusion. CONCLUSION: The intravenous route may not be the best way to administer this drug as no short term benefits were observed.

4-Aminopyridine↗

Noise-enhanced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy.

OBJECTIVE: To test the hypothesis that vibrotactile detection thresholds in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly reduced with the introduction of mechanical noise. DESIGN: A randomized controlled study. SETTING: A university research laboratory. PARTICIPANTS: Twelve healthy elderly subjects (age range, 67-85y), 5 patients with stroke (age range, 24-64y), and 8 patients with diabetic neuropathy (age range, 53-77y). INTERVENTIONS: Each subject's detection thresholds (ie, minimum level of stimulus to be detected) for a vibrotactile stimulus without and with mechanical noise (ie, random vibration with a small intensity) were determined by using a 4-, 2-, and 1-stepping algorithm. The stimuli were applied to the fingertip and/or to the first metatarsal of the foot. MAIN OUTCOME MEASURE: Detection threshold for a vibrotactile stimulus. RESULTS: The detection threshold at the fingertip for the vibration stimulus with mechanical noise was significantly lower than that without mechanical noise for all 12 elderly subjects, for 4 of the 5 patients with stroke, and all 8 patients with diabetic neuropathy. For the 8 patients with diabetes, mechanical noise also significantly reduced the vibrotactile detection threshold at the foot. CONCLUSIONS: Reduced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly improved with input mechanical noise. Noise-based techniques and devices may prove useful in overcoming age- and disease-related losses in sensorimotor function.

Adult↗

Mirror-reversal phenomena in the cutaneous perception and writing of children.

When a letter is drawn on the forehead, it is perceived cutaneously as a mirror reversal of the experimenter-defined stimulus. An analogous mirror-reversal phenomenon is found in motor behaviour; eg, writing on the downward-facing horizontal surface of a table. We examined these mirror-reversal phenomena in tasks, performed by 4-year-old and 8-year-old children, involving cutaneous perception and motor-production. The children's tendencies toward mirror reversal in the two tasks varied with the orientation and position of the surface, but were similar to those of sighted and blind adult subjects. In addition, mirror reversal was independent of the left-right indifference often observed in young children in writing or visual-matching tasks. The implications of these findings are discussed in the context of a body schema used to guide sensorimotor functions.

Attention↗

Construct validity of the Kendrick Battery with institutionalized aged.

In this study, we attempted to explore the construct validity of the Kendrick Battery by using an American sample and psychometric tests as indexes of diffuse organicity, depression, and normality. Institutionalized residents (N = 53) were tested twice (6-week interval). When organicity was defined by disorientation and memory deficits, then both the Object Learning test and the Digit Copying test were accurate in differentiating preestablished criterion groups. When organicity was defined more broadly, including sensorimotor function, the Digit Copying test alone was more accurate when depression was defined in terms of irritability, restlessness, and despair. These data suggest that although the Kendrick scales appeared to be sensitive to organicity and depression in this sample, their validity varied with the criteria for each when such were defined psychometrically.

Aged↗

Reliability associated with the abstraction of data from medical records for inclusion in an information system for persons with a traumatic brain injury.

OBJECTIVE: This article presents the intra- and inter-rater reliability associated with the extraction, from medical rehabilitation charts, of data to be included in a head injury information system currently under development. METHODS: A data collection form was developed to facilitate and standardize the data extraction. Two clinicians extracted information pertaining to 231 variables of the system from 15 charts of persons receiving rehabilitation services following a head injury. RESULTS: Average percentage agreement was high and did not vary from one category of variables to the other (84-88%). Substantial intra-rater agreement (kappa = 0.66) and moderate inter-rater agreement (kappa = 0.56) were found to be associated with the extraction of the variables studied. CONCLUSIONS: The results suggest that clinicians using standardized procedures can reliably extract important data pertaining to personal history, impairments, and disabilities relating to sensorimotor function. Some potential sources of error are identified and recommendations are presented.

Abstracting and Indexing↗

Cortical-organization in moles: evidence of new areas and a specialized S2.

The somatosensory cortex of several mole species (family Talpidae), with different peripheral sensory adaptations, was investigated and compared to determine common and specialized features of cortical organization. Previously unidentified medial representations of the trunk and limbs were found in all species, indicating that S1 in moles occupies a medial to lateral strip of cortex as in most other mammals. This finding suggests a large lateral forelimb representation, previously attributed to S1, is actually part of S2. In the face representation, evidence was found for three representations of the unusual nose of the star-nosed mole (Condylura cristata). Each of these areas was divided into a series of modules (visible in cytochrome oxidase processed tissue) representing individual nasal appendages on the star. In the closely related but less specialized eastern mole (Scalopus aquaticus) and coast mole (Scapanus orarius), only two nose representations were identified in an area of cortex with a more uniform histological appearance. The results indicate that moles have enlarged somatosensory representations of the glabrous nose as compared to shrews and rats that instead have large vibrissal representations. In addition moles have a very large and specialized representation of the digging forepaw in S2. Since this part of S2 projects directly to the cervical spinal cord, the specialization may provide adaptive sensorimotor functions related to digging.

Animals↗

Perceptions of effort and heaviness during fatigue and during the size-weight illusion.

Previous work has shown that force perception and the sense of motor effort are different attributes of sensorimotor function. This study explores the hypothesis that one reason force and effort perceptions are distinct is to inform an individual of impaired motor function when muscular force lags effort. This hypothesis predicts that effort and force perceptions will dissociate when motor function is impaired by fatigue but not during the size-weight illusion. All subjects reported a distinct increase in effort when lifting a standard test weight as fatigue developed. When fatigue was sufficiently marked so that they could barely lift the test weight, they rated their effort as similar to that required to lift a maximal weight in the unfatigued state. The perceived heaviness of the test weight also increased as fatigue developed, but this fatigue-weight illusion was smaller than the increase in effort for all subjects and displayed greater variability. In contrast, both the perceived weight of a small object and the effort required to lift it increased in parallel when small and large objects were lifted sequentially. The size-weight and size-effort illusions appear to be examples of a common phenomenon in which perceptual experience is rescaled to maintain acuity under different working conditions. The fatigue-weight illusion also has the effect of increasing perceptual acuity as the subject's weight lifting range decreases due to fatigue.

Adolescent↗

Neurological deficits induced by malathion, DEET, and permethrin, alone or in combination in adult rats.

Malathion (O,O-dimethyl-S-[1,2-carbethoxyethyl]phosphorodithionate), DEET (N,N-diethyl-m-toluamide), and permethrin [(+/-)-cis/trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylic acid (3-phenoxyphenyl) methyl ester] are commonly used pesticides. To determine the effects of the dermal application of these chemicals, alone or in combination, the sensorimotor behavior, central cholinergic system, and histopathological alterations were studied in adult male Sprague-Dawley rats following a daily dermal dose of 44.4 mg/kg malathion, 40 mg/kg DEET, and 0.13 mg/kg permethrin, alone and in combination for 30 d. Neurobehavioral evaluations of sensorimotor functions included beam-walking score, beam walk time, inclined plane, and grip response assessments. Twenty-four hours after the last treatment with each chemical alone or in combination all behavioral measures were impaired. The combination of DEET and permethrin, malathion and permethrin, or the three chemicals together resulted in greater impairments in inclined performance than permethrin alone. Only animals treated with a combination of DEET and malathion or with DEET and permethrin exhibited significant increases in plasma butyrlcholinesterase (BChE) activity. Treatment with DEET or permethrin alone, malathion and permethrin, or DEET and permethrin produced significant increases in cortical acetylcholinesterase (AChE) activity. Combinations of malathion and permethrin or of DEET and permethrin produced significant decreases in midbrain AChE activity. Animals treated with DEET alone exhibited a significant increase in cortical m2 muscarinic ACh receptor binding. Quantification of neuron density in the dentate gyrus, CA1 and CA3 subfields of the hippocampus, midbrain, brainstem, and cerebellum revealed significant reductions in the density of surviving neurons with various treatments. These results suggest that exposure to real-life doses of malathion, DEET, and permethrin, alone or in combination, produce no overt signs of neurotoxicity but induce significant neurobehavioral deficits and neuronal degeneration in brain.

Acetylcholinesterase↗

Dissociated active and passive tactile shape recognition: a case study of pure tactile apraxia.

Disorders of tactile object recognition (TOR) may result from primary motor or sensory deficits or higher cognitive impairment of tactile shape representations or semantic memory. Studies with healthy participants suggest the existence of exploratory motor procedures directly linked to the extraction of specific properties of objects. A pure deficit of these procedures without concomitant gnostic disorders has never been described in a brain-damaged patient. Here, we present a patient with a right hemispheric infarction who, in spite of intact sensorimotor functions, had impaired TOR with the left hand. Recognition of 2D shapes and objects was severely deficient under the condition of spontaneous exploration. Tactile exploration of shapes was disorganized and exploratory procedures, such as the contour-following strategy, which is necessary to identify the precise shape of an object, were severely disturbed. However, recognition of 2D shapes under manually or verbally guided exploration and the recognition of shapes traced on the skin were intact, indicating a dissociation in shape recognition between active and passive touch. Functional MRI during sensory stimulation of the left hand showed preserved activation of the spared primary sensory cortex in the right hemisphere. We interpret the deficit of our patient as a pure tactile apraxia without tactile agnosia, i.e. a specific inability to use tactile feedback to generate the exploratory procedures necessary for tactile shape recognition.

Adult↗

Postural stability and associated physiological factors in a population of aged persons.

A battery of 13 visual, vestibular, sensorimotor, and balance tests was administered to 95 elderly persons (mean age 82.7 years) to examine the relationships between specific sensorimotor functions and measures of postural stability. When subjects stood on a firm surface, increased body sway was associated with poor tactile sensitivity and poor joint position sense. When subjects stood on a compliant surface (which reduced peripheral sensation) with their eyes open, increased body sway was associated with poor visual acuity and contrast sensitivity, reduced vibration sense, and decreased ankle dorsiflexion strength as well as reduced joint position sense. Increased body sway with eyes closed on the compliant surface was associated with poor tactile sensation, reduced quadriceps and ankle dorsiflexion strength, and increased reaction time. Poor performance in two clinical measures of postural stability was associated with reduced sensation in the lower limbs as measured by joint position sense, tactile sensitivity and vibration sense, reduced quadriceps and ankle dorsiflexion strength, and slow reaction times. The prevalence of vestibular impairments was high in this group, but vestibular function was not significantly associated with sway under any of the test conditions. The results suggest that reduced sensation, muscle weakness in the legs, and increased reaction time are all important factors associated with postural instability. An analysis of the percentage increases in sway under conditions where visual and peripheral sensation systems are removed or diminished, compared with sway under optimal conditions, indicated that peripheral sensation is the most important sensory system in the maintenance of static postural stability.

Aged↗

Antisense oligodeoxynucleotide to inducible nitric oxide synthase protects against transient focal cerebral ischemia-induced brain injury.

Nitric oxide (NO) has been suspected to mediate brain damage during ischemia. Here the authors studied the effects of an antisense oligodeoxynucleotide (ODN) directed against the inducible isoform of NO synthase (iNOS) in a model of transient focal cerebral ischemia in rats. Treatment consisted of seven intracerebroventricular injections of a phosphodiester/phosphorothioate chimera ODN (3 nmol each) at 12-hour intervals, and was initiated 12 hours before a 2-hour occlusion of the left middle cerebral artery and common carotid artery. Outcomes were measured three days after ischemia. When compared with animals treated with vehicle or an appropriate random non-sense control ODN sequence, the antisense treatment reduced the lesion volume by 30% and significantly improved recovery of sensorimotor functions, as assessed on a neuroscore. This effect was associated with a decrease in iNOS expression, as assessed by Western blot, a 39% reduction in iNOS enzymatic activity evaluated as Ca2+-independent NOS activity, and a 37% reduction in nitrotyrosine formation, reflecting protein nitration by NO-derived peroxynitrite. These findings provide new evidence that inhibition of iNOS may be of interest for the treatment of stroke.

Animals↗

Phantom limb phenomenon in patients with leprosy.

The phantom limb phenomenon (PLP) was studied in 42 patients with leprosy who had limb amputation and/or digital shortening; some of the patients also had another type of limb deformity, such as claw-hand or foot-drop, which did not involve significant loss of tissue. Thirty-eight (90 per cent) of the patients reported having at least one phantom limb (PL) for a missing or deformed part. Associated with each of the three types of limb defects, two descriptively and experientially distinct types of PLs were found: the paresthetic or typical (TPL) and the painless or natural (NPL). Descriptions of the TPL and the NPL are given. The findings were compared to various reports, particularly those of Stetter and Frederiks. The leprosy TPL was similar both to the PL of amputees as frequently described in the literature, and to what Stetter and Frederiks termed the PL sensations. A close correspondence, if not identity, was noted between the NPL of leprosy patients and the equivalent categories of Stetter's PL experience and Frederiks' PL as such. Included in these three designations are aspects of the PLP that are associated with the normal, intact limb; these aspects are thought to be usual concomitants of the PLP and to constitute manifestations of the persistence of the normal body image. From our findings, we conclude that for the appearance of a PLP, the actual loss of a part of a limb, whether slow or sudden, is not required, but the loss of its sensorimotor functions is sufficient.

Adult↗

Prognostic significance of cerebral status: dimensions of clinical outcome.

This report examines the relationship between a set of neurobehavioral predictor variables (premorbid cognitive-perceptual abilities, sensorimotor functions, and complex integrative skills) and three dimensions of clinical outcome (social outcome, work functioning, and rehospitalization) 2 years after discharge from inpatient treatment for a group of psychiatric disorders. Results indicated the strongest relationship was between premorbid ability levels and work performance, particularly maintaining stability of employment or work role function. This finding is discussed from the standpoint of neurological processes underlying early acquisition of basic cognitive-perceptual skills in the prediction of outcome.

Adult↗

Herniated L4-L5 disc after placement of Harrington instrumentation for a fracture of the thoracolumbar spine.

The authors report a case in which L5 radiculopathy developed acutely after surgery for placement of Harrington rod instrumentation for an L1 body fracture. Computed tomographic myelography demonstrated a large L4-L5 herniated disc that had not been present in preoperative studies. An emergency laminectomy was performed, and a large, free, subligamentous disc fragment was removed. The patient subsequently regained L5 sensorimotor function. The postoperative development of lumbar radiculopathy is an uncommon complication of Harrington rod instrumentation that may result from several biomechanical features of the instrumentation. These injuries may not be detected by intraoperative monitoring of somatosensory evoked potentials, and therefore, the postoperative neurological examination assumes a crucial role in the early diagnosis of these lesions. As our case demonstrates, these radicular deficits may be reversible if their cause is promptly recognized and treated.

Aged↗

Pathogenesis of spinal cord injury and newer treatments. A review.

Many victims of traumatic spinal cord injury (SCI) suffer immediate paralysis as well as a subsequent progressive worsening of the cord pathology. Certain sensorimotor functions that might otherwise have returned are irreversibly lost because of this delayed response. An understanding of the pathophysiology behind this progressive, self-destructive sequence is yet to be acquired; however, numerous proposals have been set forth involving processes such as edema formation, vascular changes, an inflammatory reaction, and destruction of the neuronal plasma membranes. In this review, the authors outline many of the chemical, anatomic, and functional changes associated with SCI as well as a number of treatment regimens that have been found to improve recovery from SCI (including parenteral glucocorticoid therapy, localized cord cooling, calcium channel blockers, and opiate antagonism). From this, a number of mechanisms accounting for the mediation and/or prevention of the secondary destructive response are synthesized.

Animals↗

Comparison of the phenotype of NK1R-/- mice with pharmacological blockade of the substance P (NK1 ) receptor in assays for antidepressant and anxiolytic drugs.

The phenotype of NK1R-/- mice was compared with that of acute pharmacological blockade of the tachykinin NK1 receptor on sensorimotor function and in assays relevant to depressive illness and anxiety. The dose range for L-760735 and GR205171 that was associated with functional blockade of central NK1 receptors in the target species was established by antagonism of the behavioural effects of intracerebroventricular NK1 agonist challenge in gerbils, mice and rats. The caudal grooming and scratching response to GR73632 was absent in NK1R-/- mice, confirming that the receptor had been genetically ablated. There was no evidence of sedation or motor impairment in NK1R-/- mice or following administration of L-760735 to gerbils, even at doses in excess of those required for central NK1 receptor occupancy. In the resident-intruder and forced swim test, the behaviour of NK1R-/- mice, or animals treated acutely with L-760735 or GR205171, resembled that seen with the clinically used antidepressant drug fluoxetine. However, the effects of GR205171 were not clearly enantioselective in mice. In contrast, although NK1R-/- mice also exhibited an increase in the duration of struggle behaviour in the tail suspension test, this was not observed following pharmacological blockade with L-760735 in gerbils or GR205171 in mice, suggesting that this may reflect a developmental alteration in the knockout mouse. There was no effect of NK1 receptor blockade with L-760735 in guinea-pigs or GR205171 in rats, or deletion of the NK1 receptor in mice, on behaviour in the elevated plus-maze test for anxiolytic activity. These findings extend previous observations on the phenotype of the NK1R-/- mouse and establish a broadly similar profile following acute pharmacological blockade of the receptor. These studies also serve to underscore the limitations of currently available antagonists that are suitable for use in rat and mouse behavioural assays.

Animals↗

Brain activation studies on visual-vestibular and ocular motor interaction.

Despite their different sensorimotor functions, saccades, pursuit eye movements, small-field optokinetic nystagmus and visual motion stimulation with the eyes stationary evoke a common complex pattern of activation in various cortical, basal ganglia, brain-stem and cerebellar areas. On closer inspection, however, typical subregions can be delineated that allow differentiation of adjacent but separate loci for specific functions (e.g. the separation of the two parallel corticocortical systems to control saccades and pursuit in the cortical eye fields). It is becoming increasingly clear that stimulation of one sensory system affects other sensory systems, and generally this is via an inhibitory reciprocal mode of interaction. For example, vestibular stimulation deactivates the visual cortex and visual stimulation deactivates the vestibular cortex.

Animals↗

Evaluation of saccadic eye movements as an objective test of recovery from anaesthesia.

Saccadic eye movements have been previously used to assess residual effect of anaesthetics, but this test is seldom compared to other psychomotor tests. The aim of the present study was to validate saccades as a recovery index in relation to frequently referred subjective and psychometric tests. Eight healthy subjects were tested before and after intra-muscular injection of either placebo or 0.15 mg.kg-1 of midazolam. Each session consisted of a saccadic test (recorded by electro-oculography), a choice-reaction-time test (CRT), a subjective state-of-alertness test (11 visual analogic scales) and blood sampling (to monitor midazolam plasma concentration), before and 30 (t30), 60 (t60), 120 (t120), 180 (t180), 240 (t240) minutes after drug administration. In the placebo group, there was no change in subjective assessment, saccade characteristics (latency, peak velocity and duration) or CRT results. In the midazolam group, 6 subjective items changed with different time-courses, when compared to baseline: from t30 to t120 (drowsy, in shape, tired, clumsy, strong) and t120 (woolly). Saccade latency and duration were significantly different from t30 to t120 and until t180 for peak velocity. CRT performance was significantly altered from t30 to t120. Midazolam plasma concentration decreased from 177 +/- 33 ng.ml-1 at t30 to 47 +/- 12 ng.ml-1 at t240. At this latter time, sensorimotor functions returned to the baseline. All subjects fulfilled the clinical conditions for home discharge 4 hours after administration. These results suggest that a saccadic eye movement test is a sensitive and reliable tool for the assessment of residual effect of anaesthetics. This test was found to be more sensitive than CRT test since peak saccadic velocity was the last psychometric parameter to be returned to baseline after midazolam injection. This study also confirms the poor reliability of subjective assessment, as subjects tended to underestimate the alteration of their performance immediately following drug injection.

Adult↗