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Rehabilitative therapies after spinal cord injury.

We review some basic and highly relevant concepts in the effort to develop improved rehabilitative interventions for subjects with spinal cord injury (SCI). Interventions that are likely to contribute to improved sensorimotor function include (1) practice of the specific motor task that needs to be improved; and (2) combining the training with one or more interventions--such as pharmacological modulation of the excitability of spinal neural networks, implantation of selected cell types such as olfactory ensheathing glia (OEG), and/or modulation of the excitability of the spinal cord via epidural stimulation. Upon improvement of the neural control of the musculature following SCI, it will always be prudent to maximize the torque output from these activation patterns by assuring that muscle mass is maintained. Therefore, it seems quite feasible that considerable improvement in locomotor performance can be achieved by improved coordination of motor pools, as well as effective recovery of muscle mass, which will assist in the potential generation of normal forces among agonistic and antagonistic muscle groups.

Animals↗

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↗

Primary hypothalamic lymphoma with panhypopituitarism presenting as stiff-man syndrome.

We report an unusual case of primary hypothalamic lymphoma with hypopituitarism presenting as Stiff-man syndrome (SMS). A 64-year-old man was hospitalized due to a 3-week history of general weakness, anorexia, vomiting, weight loss, and muscle pain and spasms precipitated by motion and tactile stimuli resulting in muscle stiffness and difficulty in mobility. Physical examination revealed normal sensorimotor function and reflexes, except for bitemporal visual field defect. Routine laboratory and gastrointestinal examinations provided no remarkable clues. Endocrine assessment revealed low levels of morning cortisol, thyroxine, and anterior pituitary hormones but an increase in prolactin level. The patient's muscle pain and stiffness improved dramatically within 2 days after hydrocortisone therapy and thyroxine replacement. Magnetic resonance imaging (MRI) of the brain confirmed an 18-mm enhancing hypothalamic tumor with optic chiasm involvement, which proved to be a B-cell lymphoma. The results of the extensive studies for systemic lymphoma were negative, suggesting a primary hypothalamic lymphoma. The tumor regressed completely and was invisible on MRI scan after adjuvant radiotherapy. The patient's condition was satisfactory and there was no recurrence of SMS during the 2-year follow-up period. This case demonstrated that primary hypothalamic lymphoma complicated with adrenal insufficiency may manifest as SMS. Early diagnosis and prompt intervention can lead to a favorable outcome and reduce morbidity.

Adrenal Insufficiency↗

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↗

Behavioral phenotypes and pharmacology in genetic mouse models of Parkinsonism.

Prior to the discovery of genes associated with familial forms of Parkinson's disease, animal models of Parkinson's disease mainly consisted of toxin models based exclusively on the degeneration of nigrostriatal dopamine neurons. These traditional models have provided valuable insight into symptomatic treatments for Parkinson's disease; however, they lack the broad extra-nigral pathology and the progression that is observed in the disease. The novel genetic mouse models recently generated are advantageous because they have mutations that are known to cause familial Parkinson's disease and thus they have good construct validity. To maximize the utility of these models, a thoughtful phenotypical characterization is important. Our laboratory has assembled a battery of behavioral tests to assess sensorimotor function in genetic mouse models of Parkinsonism. This review discusses the sensitivity of these tests in different genetic mice in addition to their behavioral response to dopamine agonists.

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↗

Environmental enrichment reverses learning impairment in the Morris water maze after focal cerebral ischemia in rats.

Cognitive impairment is common after ischemic stroke. In rodent stroke models using occlusion of the middle cerebral artery (MCA) this is reflected by impaired spatial memory associated with the size of the ischemic lesion. Housing in an enriched environment enhances brain plasticity and improves recovery of sensorimotor functions after experimental stroke in rats. In this study we report that postischemic housing in an enriched environment also attenuates the long-term spatial memory impairment after MCA occlusion and extinguishes the association between spatial memory and infarct volume. An enriched environment did not significantly alter the expression of selected neuronal plasticity-associated genes 1 month after MCA occlusion, indicating that most of the adaptive changes induced by an enriched environment have already occurred at this time point. We conclude that the attenuated memory impairment induced by environmental enrichment after MCA occlusion provides a useful model for further studies on the neurobiological mechanisms of recovery of cognitive functions after ischemic stroke.

Animals↗

The pathophysiology of faecal spotting in obese subjects during treatment with orlistat.

BACKGROUND: The intermittent loss of oil or liquid faeces ('spotting') is an adverse effect that occurs in obese patients during treatment with the lipase inhibitor orlistat; the pathophysiology is unknown. AIM: To investigate the effects of orlistat on anorectal sensorimotor function and continence. METHODS: Obese subjects susceptible to spotting were identified by an unblind trial of orlistat. Obese spotters (n = 15) and non-spotters (n = 16) completed a randomized, double-blind, cross-over trial of orlistat and placebo. Anorectal function was assessed by rectal barostat and anal manometry, together with a novel stool substitute retention test, a quantitative measurement of faecal continence. RESULTS: Orlistat increased stool volume and raised faecal fat and water. Treatment had no effect on anorectal motor function, but rectal sensation was reduced; on retention testing, the volume retained was increased. Subjects susceptible to spotting had lower rectal compliance, heightened rectal sensitivity and weaker resting sphincter pressure than non-spotters. On retention testing, gross continence was maintained; however, spotters lost small volumes of rectal contents during rectal filling. CONCLUSION: Treatment with orlistat has no direct adverse effects on anorectal function or continence. Spotting occurs during treatment with orlistat when patients with sub-clinical anorectal dysfunction are exposed to increased stool volume and altered stool composition.

Adult↗

Day-to-day reproducibility of anorectal sensorimotor assessments in healthy subjects.

The reproducibility of tests widely utilized to assess anorectal sensorimotor functions is not well established. Our aims were to assess the intra-individual day-to-day reproducibility of these parameters in healthy subjects. Anal sphincter pressures were assessed by perfusion manometry on two separate days in 19 healthy subjects. Rectal pressure-volume (p-v) curves and sensory thresholds were assessed in 12/19 subjects by inflating a highly compliant polyethylene balloon from 0 to 32 mmHg in 4 mmHg steps. Subjects also rated intensity of perception by visual analogue scale (VAS) during phasic distentions 8, 16 and 24 mmHg above operating pressure, in randomized sequence. Resting and squeeze anal pressures and rectal compliance were highly reproducible (r(s) > or = 0.7) in the same subject on separate days. Pressure thresholds for urgency appeared less reproducible than thresholds for initial perception and the desire to defecate. VAS scores were highly reproducible only during the 24-mmHg distention. Thus, anal pressures and rectal compliance are highly reproducible within healthy subjects on separate days, while sensory thresholds are reproducible to a variable degree, dependent on the intensity of stimulation and the perception being assessed.

Adult↗

Behavioural and histopathological alterations in mice with cerebral malaria.

Different features of sensorimotor function and behaviour were studied in murine cerebral malaria (CM) and malaria without cerebral involvement (non-CM) applying the primary screen of the SHIRPA protocol. Histopathological analysis of distinct brain regions was performed and the relative size of haemorrhages and plugging of blood cells to brain vasculature was analysed. Animals suffering from CM develop a wide range of behavioural and functional alterations in the progressive course of the disease with a statistically significant impairment in all functional categories assessed 36 h prior to death when compared with control animals. Early functional indicators of cerebral phenotype are impairments in reflex and sensory system and in neuropsychiatric state. Deterioration in function is paralleled by the degree of histopathological changes with a statistically significant correlation between the SHIRPA score of CM animals and the mean size of brain haemorrhage. Furthermore, image analysis yielded that the relative area of the brain lesions was significantly larger in the forebrain and brainstem compared with the other regions of interest. Our results indicate that assessment of sensory and motor tasks by the SHIRPA primary screen is appropriate for the early in vivo discrimination of cerebral involvement in experimental murine malaria. Our findings also suggest a correlation between the degree of functional impairment and the size of the brain lesions as indicated by parenchymal haemorrhage. Applying the SHIRPA protocol in the functional characterization of animals suffering from CM might prove useful in the preclinical assessment of new antimalarial and potential neuroprotective therapies.

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↗

The effect of a 12-month exercise trial on balance, strength, and falls in older women: a randomized controlled trial.

OBJECTIVE: To determine whether a 12-month program of regular exercise can improve balance, reaction time, neuromuscular control, and muscle strength and reduce the rate of falling in older women. DESIGN: A randomized, controlled trial of 12 months duration. SETTING: Conducted as part of the Randwick Falls and Fractures Study in Sydney, Australia. PARTICIPANTS: One hundred ninety-seven women aged 60 to 85 years (mean age 71.6, SD = 5.4) who were randomly recruited from the community. OUTCOME MEASURES: Accidental falls, postural sway, reaction time, neuromuscular control, and lower limb muscle strength. MAIN RESULTS: Exercise and control subjects were tested before, midway through, and at the end of the trial. At initial testing, exercisers and controls performed similarly in all tests and were well matched in relevant health and lifestyle factors. The mean number of classes attended for the 75 exercise subjects who completed the program was 60.0 (range 26-82). At the end of the trial, the exercise subjects showed improved performance in all five strength measures, in reaction time, neuromuscular control, body sway on a firm surface with the eyes open, and body sway on a compliant surface with the eyes open and closed. In contrast, there were no significant improvements in any of the test measures in the controls. In one test measure, hip flexion strength, the exercisers showed continued improvement throughout the study year. There was no significant difference in the proportion of fallers between the exercise and control subjects. Interesting trends were evident, however, between falls frequency and adherence to the exercise program. CONCLUSIONS: These findings show that exercise can produce long-term benefits with regard to improving sensorimotor function in older persons. The findings also suggest that high compliance to an exercise program may reduce falls frequency, although further studies are required to conclusively demonstrate that exercise offers an effective means of preventing falls.

Accidental Falls↗