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End-to-side nerve grafting of the tibial nerve to bridge a neuroma-in-continuity.

Standard treatment for a neuroma-in-continuity with partial retained function is neurolysis with or without grafting. The present study tests the outcome of a novel partial nerve lesion bypassed with an end-to-side bridge graft, intended to increase the number of axons crossing the defect while not disturbing intact axons. An 8-mm portion of tibial nerve was resected in 20 rats. Three weeks later, half had the defect repaired with an end-to-side bridge allograft and perineurial windows; controls had only neurolysis. Recovery was evaluated using walking-track analysis, allodynia testing, muscle weight ratios, and histology at 8 weeks. No significant differences in motor or sensory functional recovery were noted between the two groups. Histology showed good axonal regeneration through the defect in all specimens. The experimental group also had regenerated axons in the bridge graft, but their maturity was less advanced, presumably due to delays in regeneration.

Animals↗

Can segregation within the semantic system account for category-specific deficits?

Functional neuroimaging was used to investigate the extent to which category-specific semantic deficits in patients can be accounted for in terms of the demands placed on neural systems underlying different types of semantic knowledge. Unlike previous functional imaging studies of category specificity, we used a factorial design that crossed category (tools and fruits) with tasks requiring retrieval of either action or perceptual (real life size) knowledge. The presentation of tools relative to fruit increased activation in the same left posterior middle temporal area that was linked to the retrieval of action knowledge in general (for fruit as well as tools). However, we found no correlation between activation evoked by fruit and the size retrieval task. The left medial anterior temporal cortex was the only region to be activated for fruit relative to tools. We argue that the sensory-functional theory of category-specific effects is insufficient to account for the current neuroimaging literature. However, the data do support a more refined version of the theory: tools, relative to fruit, are more strongly linked to manipulative/motor knowledge and, for some tasks, fruit may be more reliant on integrating multiple semantic features.

Adult↗

Only early intervention with gamma-aminobutyric acid cell therapy is able to reverse neuropathic pain after partial nerve injury.

Pharmacological treatment for neuropathic pain, although often effective for brief periods, can result in intractable persistent pain with certain patients. Cell therapy for neuropathic pain is a newly developing technology useful for an examination of enhanced normal sensory function after nerve injury with the placement of cells near the spinal cord, and grafts of immortalized cells bioengineered to chronically supply the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) have been used to reverse the chronic pain behaviors. However, it is not known whether there is a therapeutic window for the use of intervention with cell therapy after partial nerve injury. To investigate whether neuropathic pain is sensitive to the timing of placement of cell grafts, neuronal cells bioengineered to synthesize GABA were transplanted in the lumbar subarachnoid space one to four weeks after unilateral chronic constriction injury (CCI) of the sciatic nerve and sensory behaviors were evaluated before and after CCI and transplants. Both thermal hyperalgesia and tactile allodynia were reversed when transplants were placed either one or two weeks after partial nerve injury, compared to maintenance of these behaviors with the injury alone. However, if GABA cells were placed any later than 2 weeks after nerve injury, such intervention was ineffective to reverse the thermal and tactile hypersensitivities induced by the injury. This suggests that altered spinal GABA levels may contribute to the early development of chronic neuropathic pain and that early intervention with cellular therapy to restore GABA may prevent the development of that pain.

Animals↗

Antiepileptic drugs and peripheral nerve function: a multicenter screening investigation of 141 patients with chronic treatment. Collaborative Group for the Study of Epilepsy.

One hundred forty-one adult patients treated for no less than 6 months with standard daily doses of the commonest antiepileptic drugs (AEDs) were recruited in five Italian centers and submitted to intensive clinical and electrophysiologic investigation to assess the effects of AEDs on peripheral nerves. Eighty percent of the patients were receiving monotherapy. Carbamazepine (CBZ) was the most common AED (51 cases), followed by phenytoin (PHT) (46), phenobarbital (PB) (42), and valproate (VPA) (25). Fifty-three percent of the patients had one or more symptoms of polyneuropathy (paresthesias being the most common complaint). The neurologic examination was abnormal in 32%. Electrophysiologic findings in two or more separate nerves were abnormal in 77 patients (54.6%); of these, 27 (19.1%) had abnormal neurologic findings and 21 (14.9%) also had symptoms of polyneuropathy. Sensory functions were most frequently impaired. Sural nerve biopsy was performed in 4 patients receiving monotherapy with CBZ, PHT, PB, and VPA. Except in patients receiving VPA (in whom no morphologic abnormalities were detected), mild predominantly axonal damage with secondary myelin changes was noted. A correlation was noted between polyneuropathy, age of the patient and, to a lesser extent, receipt of two or more AEDs.

Adult↗

Combining motor training with transplantation of rat bone marrow stromal cells does not improve repair or recovery in rats with thoracic contusion injuries.

Previous studies have demonstrated that either transplantation of bone marrow stromal cells (MSC) or physical exercise regimens can elicit limited functional recovery following spinal cord injury, presumably through different mechanisms. The present study examined whether transplantation of MSC derived from transgenic Fischer alkaline phosphatase (AP) rats, in combination with exercise, would have synergistic effects leading to recovery of function that is greater than either alone. Adult female Sprague-Dawley rats received a moderate thoracic contusion injury and were divided into three groups: operated controls (Op-Control), MSC transplant recipients (MSC), and MSC transplant recipients plus exercise (MSC+Ex). Nine days after contusion, a Vitrogen matrix +/-one million MSC was injected into the lesion site in all animals. Immunosuppression with high doses of Cyclosporine A, required for MSC survival, was provided for all animals. Passive hindlimb exercise on motorized bicycles was applied 1 h/day, 3 days/week to the MSC+Ex group. A battery of behavioral tests was performed weekly to assess motor and sensory functions in all 3 groups for 12 weeks. Morphological evaluation included MSC survival, evidence of axonal growth into grafts, phenotypic analysis of MSC, and lesion/transplant size. The weight of the medial gastrocnemius muscle, a hindlimb muscle activated during stance, was used to identify extent of atrophy. No differences in motor recovery were found among the three groups. MSC survived 3 months after transplantation, indicating that the immunosuppression treatment was successful. The extent of survival was variable, and there was no correlation between MSC survival and behavioral scores. The matrix persisted, filling the lesion cavity, and some axons grew into the lesion/matrix but to a similar extent in all groups. There was no difference in lesion/matrix size among groups, indicating no neuroprotective effect on the host provided by the treatments. Immunocytochemical analysis provided no evidence that MSC differentiated into neurons, astrocytes or oligodendrocytes. Muscle mass of the medial gastrocnemius was diminished in the Op-Control group indicating significant atrophy, but was partially preserved in both the MSC and MSC+Ex groups. Our results indicate that combining the beneficial effects of rat MSC and this exercise protocol was not sufficient to enhance behavioral recovery.

Animals↗

Evaluation of techniques for assessing neurobehavioral development in children.

A battery of tests has been designed to explore functional disabilities in children 10-12 years of age arising from adverse conditions during early development. At these ages, it becomes possible to use more complex and challenging tests than those typically used at earlier ages. Although the battery was prompted originally by questions arising from methylmercury exposure, it was also designed for applicability to neurotoxicant exposures arising from pesticides, solvents, persistent organic pollutants such as PCBs and dioxins, other metals, and nutrient excesses and deficiencies as well. The test battery includes the following categories: (1) neuropsychological tests with established psychometric properties not widely exploited in studies of developmental neurotoxicity; (2) electrophysiological and behavioral tests of sensory functioning spanning a broader range of indices than those used generally in studies of neuropsychological development; and (3) adaptations of performance tasks used previously only in animals. The battery was developed in Rochester, New York, and then field-tested on a group of 61 children in the Republic of the Seychelles, where the Ministry of Health had established the Child Development Center. Our findings suggest a number of tests and procedures with the potential for inclusion in test batteries aimed at the exploration of adverse neurodevelopmental effects.

Adolescent↗

Experimental sensory reinnervation of the median nerve by nerve transfer in monkeys.

Anastomosis of the superficial radial nerve, the dorsal cutaneous branch of the ulnar nerve, or both to the distal cut end of a widely resected median nerve in monkeys was followed by successful sensory reinnervation of the thumb, index finger, and long finger within thiry-five to forty weeks. Success was ascertained by the presence of an intact anastomosis as observed grossly without any evidence of spontaneous regeneration of the median nerve. Reinnervation was confirmed by histological and histochemical reactions observed in the Meissner's corpuscles in the skin innervated by the median nerve. The demonstration of nerve fiber and the presence of normal specific and non-specific cholinesterase reactions exhibited by the Meissner's corpuscles in the cholinesterase preparations were considered the histological criteria for successful reinnervation. These histological and histochemical observations may explain the reported functional sensory recovery in clinical cases when similar nerve transfers were done.

Animals↗

Sensory capacity of the royal college of surgeons rat.

PURPOSE: To apply noninvasive tests for examining visual and other sensory functions of pigmented Royal College of Surgeons (RCS) rats compared with pigmented and albino control animals. METHODS: Rats aged 3 and 7 months were tested with a general neurologic examination that assessed visual, auditory, tactile, and whisker displacement responses. Photophobic responses and visual discrimination were also measured. RESULTS: Dystrophic RCS rats failed the visual presentation tests, even at 3 months of age, and showed diminished performance on tactile tests. Auditory and whisker displacement performances were normal. Albino rats also showed diminished performance on the visual test, particularly to stimuli presented in the upper visual field. Photophobic responses were diminished in the dystrophic RCS rats compared with the pigmented control animals. Albino animals showed heightened photophobia. The dystrophic rats failed to reach criterion levels of performance on the visual discrimination test even with gratings of 0.045 cyc/deg. CONCLUSIONS: The tests used discriminate deteriorated complex visual functions in RCS rats at ages when some simple reflexes can still be demonstrated. As such, they provide easily executed tests for screening for the effects of reparative treatments such as transplantation, administration of growth factors, and gene transfer technology. The integrity of whisker and auditory function are important when using tests requiring polysensory inputs. The somatosensory defect is surprising but may be useful in searching for the gene locus of the retinal disorder. The aberrations seen in the albino rats may be attributable to the effects of light damage and unfiltered light.

Animals↗

Modulation of glycine-activated ion channel function by G-protein betagamma subunits.

Glycine receptors (GlyRs), together with GABA(A) and nicotinic acetylcholine (ACh) receptors, form part of the ligand-activated ion channel superfamily and regulate the excitability of the mammalian brain stem and spinal cord. Here we report that the ability of the neurotransmitter glycine to gate recombinant and native ionotropic GlyRs is modulated by the G protein betagamma dimer (Gbetagamma). We found that the amplitude of the glycine-activated Cl- current was enhanced after application of purified Gbetagamma or after activation of a G protein-coupled receptor. Overexpression of three distinct G protein alpha subunits (Galpha), as well as the Gbetagamma scavenger peptide ct-GRK2, significantly blunted the effect of G protein activation. Single-channel recordings from isolated membrane patches showed that Gbetagamma increased the GlyR open probability (nP(o)). Our results indicate that this interaction of Gbetagamma with GlyRs regulates both motor and sensory functions in the central nervous system.

Animals↗

Biological response to noise and other physical stressors in places of entertainment.

The present study was designed in order to evaluate if the stressors produced in discotheques, and in particular high levels of noise, may lead to the impairment of some psychophysiological functions. The survey was carried out on 34 students who were exposed to noise in a discotheque (with levels ranging from 90 to 103 dBA) and to other environmental stressors (vibrations, psychedelic lights) for a period of five hours. The same subjects were examined on another day in the absence of relevant acoustical and visual stimulations. Biochemical (urinary catecholamines and cortisol) and cardiovascular (blood pressure and heart rate) indicators of stress were measured. Selected psychophysiological functions (reaction-time task and visual acuity) and some personality traits were also estimated. An increase in urinary excretion of epinephrine, norepinephrine, dopamine and cortisol was observed in most of the subjects during their presence in the discotheque in comparison to the control condition. A moderate variation was found with reference to cardiovascular parameters. No significant variation of reaction time was observed in performance tasks, while a significant impairment of visual stereoscopic perception was detected after exposure to stressors in the discotheque. The preliminary findings suggest that physical stressors, and, in particular, noise, may be related to a marked activation of the neuroendocrine system and impairment of some sensory functions.

Adult↗

Neuronal organization and cell interactions of the cat stellate ganglion.

The functional structure of the cat stellate ganglion (SG) and, in particular, its extra- and intraganglionic connections and neuronal organization, were investigated using histochemical, immunohistochemical, morphological and histological methods. Retrograde axonal transport of horseradish peroxidase was used to determine most of the extraganglionic interactions. Of the targets tested, the most extensive efferent connections of the SG were with the stemocleidomastoid muscle, trachea, esophagus and heart. Neurons of the SG also send a small number of postganglionic efferents to the thyroid and stomach. Furthermore, ganglion cells send axons to the spinal ganglia. Several afferent connections of the SG were determined. Sympathetic preganglionic neurons of segments C8-T10 of the spinal cord, sensory neurons of C8-T9 spinal ganglia, intramural ganglia of the thoracic viscera and the reticular formation of the medulla oblongata send their axons to the SG. Intraganglionic interactions of intemeurons with principal ganglionic cells were assumed to occur, based on the presence of interneurons immunoreactive to GABA and substance P. GABA- and substance P-immunoreactive fibers located around a small number of postganglionic neurons were also identified. Morphological study revealed asymmetry between the left and right ganglia: the right ganglion is larger than the left and contains more cells. This asymmetry was also reflected in basic structural parameters of neurons, such as average neuronal area and average diameter of cell somata. The present data has been used to develop a scheme for the basic inter- and intraneuronal connections of the cat SG. This ganglion is a true nervous center, with postganglionic neurons, some of which might be performing sensory functions, and interneurons. The ganglion is connected not only with the spinal cord and spinal ganglia, but also with neurons of the intramural ganglia and, by direct links, with efferent neurons of the medulla oblongata. Thus, the SG may play an essential role in viscera-visceral reflexes.

Afferent Pathways↗

Olfactory deficits in patients with schizophrenia and severe polydipsia.

BACKGROUND: The present study was designed to assess olfactory function in severely polydipsic/hyponatremic patients with schizophrenia who also had intermittent water intoxication. METHODS: The University of Pennsylvania Smell Identification Test and an olfactory acuity battery were administered to three groups of male subjects: 9 patients with schizophrenia and severe polydipsia/hyponatremia, 9 control nonpolydipsic/normonatremic patients with schizophrenia, and 9 normal controls. RESULTS: Male patients with severe polydipsia/hyponatremia and intermittent water intoxication had marked olfactory acuity and identification deficits when compared to the patient control group of similar age and age at illness onset, and to normal controls. CONCLUSIONS: The finding of deficient acuity (detection threshold) in the polydipsic/hyponatremic group but not the nonpolydipsic, normonatremic group suggests that for this subgroup, abnormalities of olfactory sensory function may occur in a pattern previously reported for other brain disorders such as Alzheimer's disease.

1-Butanol↗

Cutaneous innervation density in the allodynic form of postherpetic neuralgia.

The relationship between deafferentation, sensory function, and pain was explored in 18 subjects with chronic postherpetic neuralgia (PHN). Subjective thresholds for warmth, cooling, and heat pain were measured quantitatively in painful skin areas and compared with normal contralateral skin. The severity of allodynia was graded in the affected area. Two 3-mm punch biopsies were taken from the most painful skin area and one from unaffected contralateral mirror-image skin. Immunofluorescence with the axonal marker PGP 9.5 revealed a reduction in density of innervation of the epidermis, the dermal-epidermal junction, and the eccrine sweat glands in PHN skin. In painful PHN skin, the reduction in innervation density was positively correlated with the magnitude of the thermal sensory deficits. However, loss of cutaneous innervation was inversely correlated with allodynia, indicating that surviving cutaneous primary afferent nociceptors that are spontaneously active and/or sensitized contribute to PHN pain and allodynia.

Aged↗

Somatosensory evoked potentials and sensory involvement in multiple sclerosis: comparison with clinical findings and quantitative sensory tests.

Sensory disturbances are one of the most common findings in patients with multiple sclerosis (MS). However, they are usually assessed at the standard neurological examination only. Quantitative Sensory Tests (QSTs) for temperature and vibratory sense allow a more objective evaluation. In a group of 19 clinically definite MS patients, we compared vibratory and temperature thresholds with sensory symptoms or signs at clinical neurological examination and somatosensory evoked potentials (SEPs) at the four limbs. The frequency of abnormalities of clinical symptoms/signs, vibration threshold and median SEPs were 69%, 33% and 55%, respectively. Correlation between degree of abnormality of SEPs and clinically assessed vibration sense (V) was statistically significant (P<0.007; Spearmann rank coefficient), as well as between SEPs and vibration perception threshold (P<0.02). Clinical evaluation of thermal sense did not show false positive results compared to quantitative thermal threshold, but false negative findings (35%). This study suggests that the combined use of vibration threshold and SEPs allows a better objectivation of sensory function, allowing the detection of subclinical abnormalities and possibly reducing the number of false positive results introduced by clinical assessment. Moreover QSTs are to be preferred to clinical evaluation in the assessment of thermal sense, due to their superior sensitivity.

Adult↗

Hana Kai II: a 17-day dry saturation dive at 18.6 ATA. VII: Auditory, visual, and gustatory sensations.

Five divers were tested for alterations in auditory, visual, and gustatory functioning during a 17-day saturation exposure to He-O2 at 18.6 ATA. No evidence of permanent hearing loss was disclosed. Critical flicker fusion was not affected, but peripheral visual thresholds were significantly increased during the first two weeks at 18.6 ATA; this was interpreted to be evidence of severe psychological and physiological stress. Foveal vision was unaffected across testings. Magnitude estimation techniques disclosed changes in taste sensitivity, with sweet sensitivity increasing over time and sour sensitivity declining over the course of the dive. Subjects were more sensitive to bitter stimuli at maximum pressure than at sea level, and less sensitive to salt at maximum pressure. The results indicate that appreciable alterations in sensory functioning can occur during saturation exposures, although the sense modalities were differentially affected by such environmental stressors as pressure, psycho-social stress, fatigue, and perceptual deprivation.

Adult↗

Enlargement of cervical spinal cord correlates with improvement of motor function in upper extremities after laminoplasty for cervical myelopathy.

OBJECTIVE: The correlation between postoperative spinal cord enlargement at the most compressive disc level and clinical outcome is controversial. The relationship between spinal cord enlargement at neurologically symptomatic disc level and clinical recovery has not been explored. The purpose of this study was to clarify the relationship between postoperative spinal cord enlargement at neurologically symptomatic disc level and neurologic outcome. METHODS: We studied 55 consecutive patients between 1995 and 2002. All patients underwent preoperative neurologic examination to determine the neurologically symptomatic disc level of the spinal cord and computed tomographic myelography twice before and 4 weeks after laminoplasty. The cross-sectional areas of both spinal cord and dural sac from C3/4 to C7/T1 disc levels were measured on computed tomographic myelography images. The Japanese Orthopedic Association scoring system was used for clinical evaluation before and 1 year after surgery. RESULTS: Total score improved significantly from 10.2+/-2.8 (SD) to 13.0+/-3.0 after operation. Motor and sensory function scores of upper and lower extremities also improved significantly. The enlargement of spinal cord area at the neurologically symptomatic disc level correlated significantly with improvement in motor function scores of upper extremities (rs=0.421 P=0.0052). However, there were no significant relationships between the enlargement of the spinal cord at the most compressive disc level or that at the dural sac and any categories of Japanese Orthopedic Association scoring system. CONCLUSION: Postsurgical enlargement of the cervical spinal cord at the neurologically symptomatic disc level at 4 weeks postoperatively correlated with recovery of motor function of the upper extremities at 1 year.

Cervical Vertebrae↗

Omental transposition in chronic spinal cord injury.

The results of omental transposition in chronic spinal cord injury have been reported in 160 patients operated upon in the United States, Great Britain, China, Japan, India and Mexico, with detailed outcomes reported in few studies. Recovery of function to a greater degree than expected by natural history has been reported. In this series, 15 patients with chronic traumatic spinal cord injury (> 1.5 years from injury) underwent transposition of pedicled omentum to the area of the spinal cord injury. Of the first series of four patients who were operated upon in 1988, one died, one was lost to follow-up and two were followed with sequential neurological examinations and Magnetic Resonance Imaging (MRI) scans preoperatively, at 1 year post injury and 4 1/2 years post injury. Another 11 patients were operated in 1992 and underwent detailed neurological and neurophysiological examinations and had MRI scans preoperatively and every 4 months for at least 1 year after surgery. All patients completed a detailed self-report form. Of the total of 13 operated patients in both series followed for 1-4 1/2 years, six reported some enhanced function at 1 year and five of these felt the changes justified surgery primarily because of improved truncal control and decreased spasticity. MRI scans showed enlargement of the spinal cord as compared to preoperative scans in seven patients. Increased T2 signal intensity of the spinal cord was found by 1 year after surgery in eight of 13 operated patients. Neurophysiological examinations of 11 patients in the second series agreed with self-reports of increases or decreases in spasticity (r = 0.65, P < 0.03). Somatosensory evoked potentials and motor evoked potentials at 4 month intervals up to 1 year in these patients showed no change after surgery. Neurological testing, using the American Spinal Injury Association (ASIA) and International Medical Society of Paraplegia (IMSOP) international scoring standards, failed to show any significant changes when the 1-year post operative examination was compared to the first preoperative examination except for decreased sensory function after surgery which approached statistical significance. When the 11 patients in the second series were compared to eight non-operated matched patients, followed for a similar length of time, no significant differences were found. Complications encountered in the operated patients from both series included one postoperative death from a pulmonary embolus, one postoperative pneumonia, three chronic subcutaneous cerebrospinal fluid (CSF) fistulae requiring wound revision, and one patient who developed biceps and wrist extensor weakness bilaterally requiring graft removal. We conclude that the omental graft remains viable over time and this operation can induce anatomical changes in the spinal cord as judged by MRI. Some patients reported subjective improvement but this was not supported by objective testing. We, therefore, find no justification for further clinical trials of this procedure in patients who have complete or sensory incomplete lesions. Further testing in motor incomplete patients would seem appropriate only with compelling supportive data.

Adolescent↗

Does the chorda tympani nerve confer general sensation from the tongue?

OBJECTIVE: Patients often complain of numbness of the tongue after otologic procedures; this symptom may occur with or without taste alterations. The purpose of this study was to objectively assess possible changes in the general sensation of the tongue in patients undergoing middle ear surgery. STUDY DESIGN AND SETTING: Thirty-three individuals were included in this prospective controlled clinical study conducted at a tertiary referral center. Fifteen patients underwent middle ear surgery and 18 volunteers served as a control group. Subjects underwent objective tests to assess general sensation of the tongue before and twice after surgery. RESULTS: Forty-seven percent of the patients complained of numbness or tingling of the tongue shortly after surgery. In these patients, a significant reduction in sensitivities to light touch and 2-point discrimination on the operated side were noted at that time (P < 0.01; P < 0.009 respectively). Values returned to baseline on subsequent evaluations. No sensitivity change was noted for the contralateral hemi-tongue. CONCLUSION: Objective changes in the general sensory function of the tongue correlated with post-operative clinical symptoms experienced by patients. The results of this study support the notion that the chorda tympani nerve confers general sensation from the tongue. EBM RATING: A-1b.

Adult↗