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Stooling problems in patients with myelomeningocele.

In children with myelomeningocele fecal and urinary incontinence lowers self-esteem and decreases social interaction. The defects in the lumbosacral spine disturb the sensory and motor nerves supplying the skin and muscles of the perianal region, including the puborectalis muscle, and the external anal sphincter. The sensations in the region, as well as the motor functions of the striated muscles suffer, compromising the dynamics of continence and the normal process of stooling and leading to incontinence and constipation. Constipation has been treated by disimpaction of stools from the colon and rectum, administration of stool softeners, and a healthy diet containing adequate bulk-forming items. Incontinence has usually been managed by behavior modification of self-initiating stooling after meals and positive reinforcement of this process. This method has helped up to 75% of patients to become socially continent. Biofeedback training has been helpful in patients who have preservation of some sensorimotor functions in the perianal region and who understand and cooperate in the process of biofeedback training. The enema continence catheter has been used to empty the rectosigmoid every 48 hours; most children treated in this manner have achieved social continence. Electric stimulation of the pudendal nerves using a neuroprosthetic device has been used in some patients. The pudendal nerve is stimulated continuously to achieve continence; stimulation is discontinued only for stooling and/or urination.

Biofeedback, Psychology↗

Dose-dependent reduction of tissue loss and functional impairment after spinal cord trauma with the AMPA/kainate antagonist NBQX.

Initial studies on the role of glutamate receptors in traumatic spinal cord injury (SCI) implicated the NMDA subclass of ionotropic glutamate receptors in contributing to functional deficits. Recently we obtained evidence suggesting that non-NMDA ionotropic receptors may participate in producing a portion of the behavioral impairment after SCI. To test this hypothesis we have conducted a dose-response experiment, focally injecting 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX; 1.5, 5, or 15 nmol), a highly selective antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptors, or vehicle alone, into the injury site beginning at 15 min after a standardized contusive SCI. Behavioral tests of hindlimb reflex and coordinated sensorimotor function were performed 1 d after injury and weekly thereafter. At 4 weeks, spinal cord tissue was examined using quantitative histopathological and immunocytochemical techniques. We found a dose-dependent reduction in tissue loss at the thoracic injury site, with greater residual amounts of both gray matter and myelinated white matter. The maximum dose (15 nmol) significantly reduced the average length of the lesions and doubled the area of residual white matter at the epicenter. Serotonin immunoreactivity caudal to the lesion, used as a marker for descending motor control axons, was also increased in a dose-related manner and nearly tripled with the highest dose of NBQX as compared to controls. Most importantly, the reduced tissue loss in NBQX-treated groups was correlated with reduced functional deficits. There was a dose-dependent enhancement of speed and degree of recovery of both reflex and coordinated hindlimb motor activity, and reduction in the time required for establishing a reflex bladder. The long-term functional deficits at 4 weeks after SCI were reduced in a dose-related manner. Further, regression analyses demonstrated a significant correlation between the increase in amount of residual tissue and improvement in hindlimb function. Our results suggest that in this type of incomplete contusive SCI, a large and functionally important proportion of the tissue loss appears to be due to secondary injury mediated by local AMPA/kainate receptors.

Animals↗

Functional MR imaging assessment of a non-responsive brain injured patient.

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.

Accidents, Traffic↗

[Intracranial EEG monitoring for epilepsy surgery using electrode grids--results in the first 22 Dutch patients].

OBJECTIVE: Description of initial experiences with subdural electrode grids in patients with refractory focal epilepsy as additional diagnostic tool for epilepsy surgery. Using these electrodes, the attacks were recorded during a number of days and the cerebral cortex was electrically stimulated in order to map the functional areas. DESIGN: Retrospective. METHOD: Data were collected from patients in whom subdural electrode grids had been placed between 1 September 1999 and 31 August 2004. All patients underwent a neurological examination and a neuropsychological test before the implantation. At the follow-up examination, the results with regard to function and the frequency of attacks were noted, as well as the complications. RESULTS: Electrodes were placed in 22 patients: 9 women and 13 men with an average age of 27 years (range: 5-42). The implantation lasted for an average of 7 days (range: 3-10). In 4 patients, increased seizures during implantation required intravenous anticonvulsant treatment. Severe but transitory complications were seen in 4 patients (meningitis, subdural haematoma and ischaemia). 19 patients underwent a therapeutic resection. A postoperative decline in language skills was noted in 1 patient, while another 2 scored poorer in verbal tests. A permanent decline in sensorimotor function was seen in 1 patient, but this had been foreseen. Of the 16 operated patients with a duration of follow-up of at least 1 year, so were (practically) free of attacks, and another 3 patients had significantly fewer attacks. CONCLUSION: Registration with intracranial electrodes makes it possible to treat epileptic patients surgically by excision of brain tissue near critical areas. Such intensive monitoring is, however, not without risk and this must be weighed against the potential benefits.

Adolescent↗

An animal model of generalized nonconvulsive status epilepticus: immediate characteristics and long-term effects.

Absence seizures are traditionally believed to have no significant long-term neurological consequences, but few basic scientific studies have examined the effects of absence seizures on neuronal function, especially regarding absence status epilepticus. We developed a model of generalized nonconvulsive status epilepticus (GNCSE) in rats to study behavioral, functional, and histological effects of GNCSE. Using repetitive timed injections of low-dose pentylenetetrazol (PTZ), a state of prolonged behavioral arrest and immobility associated with frequent generalized spike-wave discharges on EEG could be induced for hours, consistent with GNCSE. GNCSE occurred reproducibly in adult rats, but surprisingly not in juvenile rats or adult mice. There was no evidence of pathological damage following GNCSE using Fluoro-Jade B and Cresyl Violet histological methods. Although a transient, subtle deficit in place learning occurred in PTZ-treated rats, there were no long-term behavioral effects of GNCSE on spatial learning or sensorimotor function. However, 1 week after a single episode of GNCSE, there was an increase in absence seizures in response to a repeat dose of PTZ compared to controls. These results indicate that an animal model of GNCSE can be generated and that even in the absence of overt neuronal damage, GNCSE may produce functional changes in neurons that alter electrical excitability of neural circuits.

Age Factors↗

Behavioural specificity of neocortical grafts of fetal basal forebrain tissue after unilateral lesion of the nucleus basalis with alpha-amino-3-OH-4-isoxozole propionic acid (AMPA).

The previous articles in this series [4,9] have shown that unilateral AMPA lesions of the nucleus basalis magnocellularis (nbm) produced widespread morphological and functional changes to the forebrain cholinergic projection system that could be reversed by transplants of fetal cholinergic tissue. At earlier postgraft time points, the effects of cholinergic grafts were specific to the neocortical region (frontal or parietal cortex) into which the grafts were targeted. Here we report that nbm lesion-induced spatial learning and memory deficits in the Morris water maze were reversed at 6-8 weeks postsurgery only by cholinergic grafts placed in the frontal cortex or frontal and parietal cortices combined. Similar grafts to parietal cortex only and noncholinergic fetal transplants to any cortical site were ineffective. In contrast, using separate groups of animals, deficits in sensorimotor function could be reversed in only one measure (open field turning) by cholinergic transplants targeted to the parietal (somatosensory) cortex or frontal and parietal cortex combined. These behavioural dissociations demonstrate that the frontal cortical cholinergic innervation from the nbm is necessary for effective spatial cognitive performance.

Animals↗

[Dyslexia-- a peculiar form of heterophoria?].

The authors discuss the problem of legasthenia--a particular impediment in the learning of fluent reading and orthographic writing. One connects it with a form of heterophoria in which the eyes--because of an inacurate and changeable function of binocular vision are unable to exert precise saccadic movements enabling a binocular or precisely unimacular reading. A childish art of following with the eyes from one detail to the other during the learning of reading must be transformed into minute fixation movements in conditions of a permanent excitation of convergence and accommodation to which the child is not accustomed. This leads sometimes to a false positioning of the eyes and in the consequence to a spatial disorganization in the succeeding set of letters. Therapeutical results show that as well legasthenia as its complications in the general behaviour of the child are receding together with the improvement of the sensorimotor functions of the eye.

Child↗

Expression of rat insulin-like growth factor binding protein-6 in the brain, spinal cord, and sensory ganglia.

Insulin-like growth factors (IGFs) are important trophic factors during development as well as in the adult or damaged nervous system. Their trophic actions are modulated by interactions with six distinct IGF binding proteins. The mRNA expression profiles of binding proteins 2, 4 and 5 in the normal developing and adult CNS are well characterized and are shown to have distinctive, non-overlapping distributions. The IGF binding protein-6 (BP6) is also expressed in the CNS, however, details regarding its mRNA expression distribution in the developing and adult nervous system is limited. BP6 has the unique property of preferentially binding the IGF-II ligand. Coupled with the fact that this ligand is the most abundantly expressed IGF in the adult CNS, this suggests that the IGF-II/BP6 complex has a unique role in modulating IGF-II function in the adult brain. In this report the anatomical distribution of BP6 messenger RNA in the developing and adult rat nervous system is presented. In the embryonic animal the CNS expression is tightly restricted to trigeminal ganglia and, relative to the rest of the embryo, this structure has the highest expression. The expression in the forebrain and cerebellum does not occur until after postnatal day 21 and then is primarily associated with GABAergic interneurons. The highest levels of expression in the adult animal are in the hindbrain, spinal cord, cranial ganglia, and dorsal root ganglia. These nuclei in the hindbrain and periphery that express BP6 are all associated with the coordination of sensorimotor function in the cerebellum, which indicates an important role for the BP6/IGF-II complex in the function and maintenance of these systems.

Animals↗

Characterization of a rat model to study acute neuroinflammation on histopathological, biochemical and functional outcomes.

Neuroinflammation is one of the events occurring after acute brain injuries. The aim of the present report was to characterize a rat model to study acute neuroinflammation on the histopathological, biochemical and functional outcomes. Lipopolysaccharide (LPS), known as a strong immunostimulant, was directly injected into the hippocampus. The spatiotemporal evolution of inducible NOS (iNOS) and cell death was studied from 6 h to 7 days. A perfect time course correlation was observed between iNOS immunoreactivity and iNOS activity showing an acute, expansive and transient iNOS induction in the hippocampus with a peak at 24 h. It was associated with a marked increase in NO metabolite (NO(x)) levels, and a high level of myeloperoxidase (MPO) activity. This inflammation precedes a massive cellular loss including at least neurons and astrocytes, and a drop of constitutive NOS activity, restrictive to the ipsilateral hippocampus from 48 h after LPS injection. Moreover, sensorimotor function impairment occurred from 24 h to 7 days with a maximum at 24 h post-LPS injection. Therefore, we characterized an in vivo model of acute neuroinflammation and neurodegeneration, in relation with a neurological deficit, which may be a powerful tool for mechanistic studies and for further evaluation of the potential neuroprotective agents.

Animals↗

Cerebral cortical processing of swallowing in older adults.

While brain-imaging studies in young adults have implicated multiple cortical regions in swallowing, investigations in older subjects are lacking. This study examined the neural representations of voluntary saliva swallowing and water swallowing in older adults. Nine healthy females were examined with event-related functional magnetic resonance imaging (fMRI) while laryngeal swallow-related movements were recorded. Swallowing in the older adults, like young adults, activated multiple cortical regions, most prominently the lateral pericentral, perisylvian, and anterior cingulate cortex. Activation of the postcentral gyrus was lateralized to the left hemisphere for saliva and water swallowing, consistent with our findings in young female subjects. Comparison of saliva and water swallowing revealed a fourfold increase in the brain volume activated by the water swallow compared to the saliva swallow, particularly within the right premotor and prefrontal cortex. This task-specific activation pattern may represent a compensatory response to the demands of the water swallow in the face of age-related diminution of oral sensorimotor function.

Aged↗

Immunoactivation and altered intercellular communication mediate the pathophysiology of spinal cord injury.

Evidence and inferences from clinical research, clinical observation, and literature review support an etiologic paradigm for the pathophysiology of spinal cord injury (SCI). According to this paradigm, changes in immunoregulation and in the activation of cytokines or intercellular adhesion molecules (ICAMs) contribute to many of the comorbidities, metabolic changes, and pathophysiologic sequelae observed after traumatic SCI. Cytokines and ICAMs are endogenously secreted molecules that serve as intercellular signals and immunoregulators. They modulate the activity of cells and influence the organization and function of tissues or organs. These intercellular signals are posited as molecular links between the damaged, decentralized nervous system of SCI and the acquired autonomic failure, neuroendocrine-immunoregulatory dysfunction, diminished central nervous system (CNS) regenerative capacity, and broad spectrum of pathology, organ failure, and generalized impairment of homeostasis caused by trauma to the spinal cord. These highly bioactive molecules may also mediate or facilitate the intralesional CNS axonal damage and peripheral neurologic deficits sustained at time of acute CNS injury. Ultimately, it should be possible to develop treatments that will block or modulate the local and systemic expression of cytokine or ICAM bioactivity. Such treatments might aid victims of SCI by diminishing overall morbidity or mortality, helping restore sensorimotor function and homeostasis, and enhancing longevity and quality of life.

Biotransformation↗

Somatosensory representation of the digits and clinical performance in patients with focal hand dystonia.

OBJECTIVE: The purpose of this study was to incorporate magnetoencephalography and clinical testing to describe differences in somatosensory organization and sensorimotor function of the hand in patients with focal hand dystonia, a target-specific disorder of voluntary movement that interferes with fine motor control during the performance of rapid, repetitive, skilled movements. DESIGN: This descriptive study included prospective, quasi-experimental comparisons between groups. RESULTS: Patients with focal hand dystonia demonstrated deficits in physical variables, sensory processing, and motor control when compared with age- and sex-matched controls. They also had altered patterns of firing (amplitude and latency integrated over time) and abnormal somatosensory representations on magnetoencephalography. CONCLUSIONS: These study findings suggest that there are alterations in both somatosensory representation of the digits and clinical performance in patients with focal hand dystonia. Future studies to determine if alterations in the sensorimotor feedback loop contribute to the development of focal hand dystonia are indicated. If so, intervention strategies may need to include specific types of somatosensory retraining as part of the rehabilitation program for patients with focal hand dystonia.

Adult↗

Sensorimotor disturbances in chronic neck pain--range of motion, peak velocity, smoothness of movement, and repositioning acuity.

The purpose of this pilot study was to evaluate sensorimotor functions in patients with chronic neck pain with objective and quantitative methods. A group of 16 patients with chronic idiopathic neck pain of insidious onset or whiplash associated disorders (WAD) was compared to an equally sized group of healthy subjects. Kinematics were investigated during voluntary head rotations by measuring range of motion, variability of range of motion (ROM-Variability), peak velocity, and smoothness of movement (jerk index). Repositioning acuity after cervical rotations was evaluated by analysing constant and variable error (VE). In comparison to the healthy subjects, the patients showed significantly larger jerk index, ROM-Variability and VE. No statistically significant differences were found between insidious neck pain and WAD. It is concluded that jerky and irregular cervical movements and poor position sense acuity are characteristic sensorimotor symptoms in chronic neck pain. The observed individuality in sensorimotor disturbances emphasizes the importance of developing specific rehabilitation programs for specific dysfunctions, and of using objective and quantitative methods for evaluation of rehabilitation.

Adult↗

A preliminary investigation on the acute pharmacodynamic effects of hypericum on cognitive and psychomotor performance.

Research has indicated that the herb St John's Wort (Hypericum perforatum) has comparable efficacy to conventional antidepressants in the treatment of depression. Although clinical studies have demonstrated that hypericum has a superior side-effect profile compared to standard antidepressants, no study has directly compared the cognitive and psychomotor effects of hypericum with those of other antidepressants. The aim of the current study was to examine the acute effects of hypericum on cognitive and psychomotor function, and to compare its effects with those of amitriptyline. Thirteen healthy volunteers received an acute dose of placebo, amitriptyline (25 mg, positive control) or hypericum (900 mg or 1800 mg) in a double-blind, placebo-controlled design. Cognitive and psychomotor tests and subjective measures of sedation were administered before and 1, 2 and 4 hours after drug administration. Amitriptyline impaired performance on a battery of psychological tests, which included critical flicker fusion (CFF), choice reaction time (CRT), digit symbol substitution test (DSST), profile of mood states (POMS) and the line analogue rating scale (LARS), while hypericum had neutral effects on performance in these tests. However, hypericum induced a dose-related impairment on DSST. Current findings suggest that clinical doses of hypericum do not impair attention, sensorimotor function or information processing.

Adult↗

Dissociating the spatio-temporal characteristics of cortical neuronal activity associated with human volitional swallowing in the healthy adult brain.

Human swallowing represents a complex highly coordinated sensorimotor function whose functional neuroanatomy remains incompletely understood. Specifically, previous studies have failed to delineate the temporo-spatial sequence of those cerebral loci active during the differing phases of swallowing. We therefore sought to define the temporal characteristics of cortical activity associated with human swallowing behaviour using a novel application of magnetoencephalography (MEG). In healthy volunteers (n = 8, aged 28-45), 151-channel whole cortex MEG was recorded during the conditions of oral water infusion, volitional wet swallowing (5 ml bolus), tongue thrust or rest. Each condition lasted for 5 s and was repeated 20 times. Synthetic aperture magnetometry (SAM) analysis was performed on each active epoch and compared to rest. Temporal sequencing of brain activations utilised time-frequency wavelet plots of regions selected using virtual electrodes. Following SAM analysis, water infusion preferentially activated the caudolateral sensorimotor cortex, whereas during volitional swallowing and tongue movement, the superior sensorimotor cortex was more strongly active. Time-frequency wavelet analysis indicated that sensory input from the tongue simultaneously activated caudolateral sensorimotor and primary gustatory cortex, which appeared to prime the superior sensory and motor cortical areas, involved in the volitional phase of swallowing. Our data support the existence of a temporal synchrony across the whole cortical swallowing network, with sensory input from the tongue being critical. Thus, the ability to non-invasively image this network, with intra-individual and high temporal resolution, provides new insights into the brain processing of human swallowing.

Adult↗

[Cognitive capacity in advanced age: initial results of the Berlin Aging Study].

This study reports data on intellectual functioning in old and very old age from the Berlin Aging Study (N = 516; age range = 70-103 years; mean age = 85 years). A psychometric battery of 14 tests was used to assess five cognitive abilities: reasoning, memory, and perceptual speed from the broad fluid-mechanical as well as knowledge and fluency from the broad crystallized-pragmatic domains. Cognitive abilities had a negative linear relationship with age, with more pronounced age-based reductions in fluid-mechanical than crystallized-pragmatic abilities. At the same time, ability intercorrelations formed a highly positive manifold, and did not follow the fluid-crystallized distinction. Interindividual variability was of about equal magnitude across the entire age range studied. There was, however, no evidence for substantial sex differences. As to origins of individual differences, indicators of sensory and sensorimotor functioning were more powerful predictors of intellectual functioning than cultural-biographical variables, and the two sets of predictors were, consistent with theoretical expectations, differentially related to measures of fluid-mechanical (perceptual speed) and crystallized pragmatic (knowledge) functioning. Results, in general indicative of sizeable and general losses with age, are consistent with the view that aging-induced biological influences are a prominent source of individual differences in intellectual functioning in old and very old age. Longitudinal follow-ups are underway to examine the role of cohort effects, selective mortality, and interindividual differences in change trajectories.

Aged↗

RC-3095, a bombesin/gastrin-releasing peptide receptor antagonist, impairs aversive but not recognition memory in rats.

Bombesin and its mammalian equivalent, gastrin-releasing peptide (GRP), stimulate cell proliferation and are involved in the pathogenesis of several types of human cancer. Bombesin-like peptides also display neuroendocrine activities and regulate neural function. In the present study, we evaluated the effects of the bombesin/GRP receptor antagonist (D-Tpi(6), Leu(13) psi[CH(2)NH]-Leu(14)) bombesin-(6-14) (RC-3095), experimental antitumor drug, on memory in rats. Adult female Wistar rats were treated with an intraperitoneal injection of RC-3095 (0.2, 1.0 or 5.0 mg/kg) 30 min before training in either inhibitory avoidance or novel object recognition tasks. Retention test trials were carried out 1.5 (short-term memory) or 24 h (long-term memory) after training. RC-3095 at the doses of 0.2 or 1.0 mg/kg, but not at the dose of 5.0 mg/kg, impaired both short- and long-term inhibitory avoidance retention, but did not affect recognition memory. The memory-impairing effect of RC-3095 could not be attributed to alterations in sensorimotor functions. The results show that the antitumor drug/GRP antagonist RC-3095 impairs formation of aversive memory.

Animals↗

Ipsilesional deficits during fast diadochokinetic hand movements following unilateral brain damage.

Impaired sensorimotor function of the hand ipsilateral to a unilateral brain lesion has been reported in a variety of motor tasks; however, elementary diadochokinetic movements, such as tapping with the index finger, seem to be preserved in chronic-lesion patients. Three different diadochokinetic movements (forearm diadochokinesis, hand tapping (HT) and finger tapping (FT)) were tested in patients with left brain damage (LBD) and right brain damage (RBD) and control subjects. Movements were measured three-dimensionally and the kinematics of joint angles were analyzed. While the patients' measures of movement speed and symmetry appeared normal, detailed kinematic analysis revealed clear deficits in several measures of movement variability, which reflected decreased regularity of the alternating movement cycles. This impairment was greater in LBD patients and tended to be greater during forearm diadochokinesis. The necessity of ipsilateral control in addition to dominant, contralateral control, especially during left hand and more complex or more proximal manual tasks may account for these findings. In addition, the role of apraxia (defined by impairments during the imitation of gestures) in the performance deficits of LBD patients was also assessed. Although, some performance decrements were associated with the presence of apraxia, these were different from the group findings and restricted to the two tapping tasks. Thus, although apraxia may have caused deficits in establishing dynamic representations of the elementary postures in conditions of high speed and low complexity, the disturbances during diadochokinetic movements must for the most part be attributed to more motor-related deficits of ipsilateral sensorimotor control, which are particularly apparent when the motor dominant left hemisphere is affected. The absence of clear correlations between performance deficits and lesion characteristics suggests that a distributed network is involved in this ipsilateral control.

Adult↗