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PubMed2006

Therapeutic potential of novel selective drugs targeting nicotinic acetylcholine receptors.

The potential therapeutic benefit of nicotinic ligands in a variety of neurodegenerative pathologies involving the CNS has energized research efforts to develop nicotinic acetylcholine receptor (nAChR) subtype-selective ligands (Bencherif and Schmitt, 2005). In particular, there has been a concerted effort to develop nicotinic compounds with selectivity for CNS nAChRs as potential pharmaceutical tools in the management of these disorders. Clinical and experimental data demonstrate a central role for alpha7 and alpha4beta2 nAChRs in cognitive function, sensory processing, mood, and neuroprotection (Bencherif and Schmitt, 2005; Buccafusco et al., 2005). The development of safe alpha7-selective ligands has been hampered by their lack of discrimination with hERG channels and 5-HT3 receptors. We have developed a number of compounds that display nanomolar affinity to the alpha7 and/or the alpha4beta2 receptor. Investigation of alpha7 functional activity showed a full range of activities from antagonists to full agonists without any significant activity at the human 5-HT3 receptor, P450 isozymes, hERG channels, or in the AMES test. Our findings demonstrate that potent and highly selective nAChR ligands can be designed.

Animals↗

PubMedDate not supplied

Multiple sclerosis of the spinal cord: diagnosis and follow-up with contrast-enhanced MR and correlation with clinical activity.

PURPOSE: Although MR findings in multiple sclerosis (MS) are well known, the relationship between MR-detected lesions and clinical activity has not been studied in the spinal cord. The purpose of this study was to determine whether serial MR imaging provides evidence of disease activity unsuspected on clinical examination and to determine whether it is useful in monitoring patients with MS primarily affecting the spinal cord. METHODS: Twenty-five consecutive patients with MS and with signs and symptoms of myelopathy underwent a full neurologic examination and contrast-enhanced MR imaging of the spinal cord at intervals of 0, 2, 6, and 12 months. Disability was rated according to Kurtzke's functional systems and the expanded disability status scale (EDSS). Clinical status of myelopathy (improved, deteriorated, or stable) was also assessed. Hyperintense lesions were counted on T2-weighted images and a weighted lesion load was calculated for each patient. The number of enhancing lesions was also determined. RESULTS: We found a moderate correlation between lesion load and sensory function and EDSS. Seventy percent of patients with new clinical manifestations of myelopathy had one or more enhancing lesions. Agreement between MR findings and clinical examination in evincing disease activity was found in 60% of follow-up examinations. MR images showed lesion progression in seven (44%) of 16 occurrences of clinical deterioration and in 21 (35%) of 60 occurrences of clinical improvement or stability. CONCLUSION: Serial MR imaging provides evidence of disease activity unsuspected on clinical examination and could be useful in monitoring patients with MS primarily affecting the spinal cord.

Adult↗

PubMed1990

Entrapment of the C2 root and ganglion by the atlanto-epistrophic ligament: clinical syndrome and surgical anatomy.

Two cases of progressive, occipital lancinating pain and dysesthesias associated with a sensory deficit of the C2 dermatome are presented. Symptoms were relieved, and C2 sensory function restored by releasing a hypertrophied atlanto-epistrophic ligament entrapping the C2 root and ganglion. The normal anatomy and abnormal surgical findings are described. C2 entrapment by the atlanto-epistrophic ligament is discussed in reference to other C2 lesions causing occipital pain. We conclude that some patients whose progressive occipital pain is accompanied by a C2 sensory deficit are suffering from entrapment of the C2 root and ganglion amenable to surgical decompression.

Adolescent↗

PubMed2004

Psychophysical assessment of patients with posttraumatic neuropathic trigeminal pain.

This article reviews the utility of psychophysical approaches in the assessment of posttraumatic neuropathic trigeminal pain. Methods of quantitative sensory testing are derived from psychophysical principles and provide a widely accepted means for characterizing sensory dysfunction in patients who experience injury to the trigeminal nerve. No published study, however, has sought to compare sensory findings from trigeminal nerve-injured patients who develop neuropathic pain with those from trigeminal nerve-injured patients who remain pain-free. Moreover, sensory testing data from trigeminal nerve-injured patients with pain have been published in only a few reports. As a result, remarkably little is known about sensory factors associated with the development of posttraumatic trigeminal neuralgia. Review of the separate literatures suggests that both trigeminal nerve-injured patients with pain and pain-free trigeminal nerve-injured patients exhibit grossly similar impairments in sensory function. In addition, trigeminal nerve-injured patients with pain may be more likely to report cold allodynia than patients without pain and to exhibit signs of central sensitization such as allodynia to light brushing tactile stimuli and abnormal temporal summation of pain. New studies using state-of-the-art psychophysical methods are needed to search for sensory markers that bear on the development of pain. Moreover, the relationship between psychophysical indices of central sensitization and measures of clinical pain should be addressed to obtain a better understanding of the underlying pathophysiology.

Case-Control Studies↗

PubMed1994

Olfactory-evoked potentials: assessment of young and elderly, and comparison to psychophysical threshold.

Olfactory-evoked potentials (OEPs) were recorded monopolarly at the Fz, Cz and Pz electrode sites in young adults and elderly subjects with an amyl acetate stimulus presented olfactometrically. Psychophysical odor thresholds for amyl acetate were determined using a two-alternative, forced-choice detection procedure. These demonstrated a decreased odor detection sensitivity in the elderly relative to tye young subjects. In accordance with the threshold findings, elderly subjects produced significantly smaller N1 and P2 amplitudes, and a trend towards longer latencies than younger subjects. Moreover, odor threshold was found to correlate with amplitude magnitude. The OEP findings, which are discussed in the context of previous OEP studies, offer promise as an objective, non-invasive measure of sensory function in both clinical and non-clinical settings.

Adult↗

PubMedDate not supplied

Epidural perfusion cooling protects against spinal cord ischemia in rabbits. An evaluation of cholinergic function.

The protective effect of regional epidural spinal cord cooling was evaluated in a rabbit spinal cord ischemia model. Hypothermia was performed by the continual perfusion of 2-4 degrees C cold saline in the epidural space around the ischemic lumbar segments, 4 min before and during ischemia. The spinal cord was deeply hypothermic (21 degrees C) throughout the whole ischemic period. Ischemia was induced by the occlusion of the abdominal aorta for 40 min under normothermic or hypothermic conditions. Recovery of motor and sensory functions, spinal cord-evoked potentials, and motor-evoked potentials were then evaluated up to 24 h postischemia. After this period, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were measured, in particular, zones of the lumbar spinal cord. AChE was also investigated histochemically. Animals in the normothermic group displayed fully developed spastic paraplegia with near complete loss of spinal somatosensory and motor-evoked potentials. AChE histochemistry showed extensive necrotic changes affecting lumbosacral gray matter. These changes corresponding with the pronounced losses of ChAT and AChE activities indicated irreversible injury of the spinal cord. In contrast, after hypothermic ischemia, animals survived without any sign of neurological impairment with almost full recovery of the spinal cord-evoked potentials. ChAT and AChE activities in the gray matter showed near control values corresponding with histochemical analysis of fully preserved gray matter. Hypothermia under the present experimental conditions efficiently protected the spinal cord against ischemic injury.

Acetylcholinesterase↗

PubMed1999

Extraocular muscle proprioceptors and proprioception.

Uncertainty of the roles of proprioception and efference copy in visual spatial perception persists. Proprioception has won back some support recently mainly on the evidence gained from physiological experiments in man, and rather than being mutually exclusive, the two mechanisms have been presented as collaborating. Another view supported by human and animal experiments states that current visual spatial perception may be served by efference copy whereas proprioception is responsible for temporal adaptations of the system. Certain characteristics of visuomotor cells of the monkey cortex can be explained assuming an efference copy input. Anatomical data from different sources are not easily reconciled. Disagreement about the nerve pathway of muscle afferents weakens arguments based on the results of open loop experiments involving nerve lesions in monkeys. The assumed presence of Golgi tendon organs in human extraocular muscles is no longer tenable and instead, palisade endings similar to those of cats and monkeys and other, irregular nerve endings are described. But man differs in having a limited and patchy distribution of neurotendonous endings and moreover, they may develop only after infancy. The allocation of a sensory function to palisade endings in myotendinous cylinders appears secure, at least in cats. Detailed examination of muscle spindles in man reveals anomalies of structure sufficient to question their capacity to provide useful proprioceptive information. One of the anomalies is the atrophy of intrafusal muscle fibres, present in both infant and adult muscles, and it is proposed that the redundant sensory endings, which do not appear to degenerate, search for new targets and may account for the random presence of tendon nerve endings. These observations place the role of proprioception in human extraocular muscles in jeopardy; they are unsupportive of the recent physiological studies and favour efference copy.

Afferent Pathways↗

PubMed1988

[Functional monocular hemianopsia].

Certain patients with reduction or loss of central visual function and/or hemianopic changes of the visual field can be classified as well-informed malingerers, individuals who are easily influenced by suggestion, or neurotics suffering from "conversion hysteria." The main symptom is one of a functional sensory change (loss or reduction of visual field). The task falling to the ophthalmologist is to prove the contrary, using certain subjective and objective tests to prove the incompatibility of the results with the physiological facts. The authors discuss the specificity of these tests in this context and present a number of cases with the characteristic temporal or nasal functional hemianopsia comparing them with patients who have hemianopsias due to real anatomic lesions.

Adolescent↗

PubMed2001

Delayed functional recovery by vincristine after sciatic nerve crush injury: a mouse model of vincristine neurotoxicity.

Neuropathy is the dose-limiting side effect of vincristine (VCR) in cancer therapy. However, no simple experimental model has yet been reported. Here, we present a simple experimental model of VCR neurotoxicity using a mouse sciatic nerve crush model, which allows evaluation within a few weeks. VCR administered intravenously once on the day after the crush lesion caused a dose-dependent delay of the recovery of motor and sensory functions. The minimal dose required to cause the delay was 0.25 mg/kg, which corresponded to five times the usual clinical dose for man and was far less than the reported doses required to cause functional impairment in intact animals. The model would be useful not only for the development of new drugs but also for the estimation of the drug interactions in combination cancer therapy.

Animals↗

PubMed1991

Regeneration of olfactory receptor cells.

The vertebrate olfactory system has become an important model for the study of neural regeneration. The most remarkable feature of this system is its unique capacity for neurogenesis and replacement of degenerating receptor neurons. This replacement is made possible by a persistent neurogenesis among basal cells. Basal cells differentiate, develop into sensory neurons and grow axon processes. Receptor cell axons project back to the olfactory bulb where they reestablish connections with the central nervous system. When mature receptors reach a critical age, are damaged by nerve injury, or are exposed to environmental agents that enter the nasal cavity, they degenerate and are subsequently replaced by newly regenerated receptor cells. Recent experiments demonstrate that olfactory neurogenesis is not simply an extension of growth and development but is a unique capacity for cell replacement that persists beyond maturity and well into old age. Even more remarkable is the finding that replacement receptor cells re-establish connections with the CNS and restore sensory function. It is expected that further studies of olfactory neurogenesis using cell and tissue culture methods will provide important advances for the field of neural regeneration.

Animals↗

PubMed1992

Quantitative sensory examination in human epidural anaesthesia and analgesia: effects of lidocaine.

To characterize the sensory effects of epidural lidocaine, 2 groups each of 10 human subjects received 25 ml of 2% lidocaine at the L1-L2/L2-L3 interspace (high lumbar group) or at the L3-L4/L4-L5 interspace (low lumbar group). Twelve quantitative sensory tests in the L5 and S1 dermatomes and leg extension strength were determined every 30 min for 3 h. Sensory and motor blockade were more pronounced in the low than in the high lumbar group. Sensory functions were blocked in the following order by epidural lidocaine: warm > cold > electrical stimuli. Perception of brief localized noxious stimuli was attenuated more than perception of noxious stimuli of longer duration and involving larger stimulus areas. It is suggested that both peripheral mechanisms (differential conduction blockade of afferent fibres) and central mechanisms (temporal and spatial summation) play a role in the sensory effects of epidural lidocaine.

Adult↗

PubMed1996

Bypass coaptation procedures for cervical nerve root avulsion.

In the past, patients with cervical spinal nerve root avulsions were resigned to accept a natural crippling from upper extremity neurological deficits. Recently, bypass coaptation procedures have resulted in functional return of denervated muscles after such avulsions, much to the appreciation of patients. Presented are 12 patients with avulsion of cervical spinal nerve roots that form either the brachial plexus upper trunk (n = 7), lower trunk (n = 1), or all three trunks (n = 4). The patients underwent the new bypass coaptation procedures with complete or partial return of motor and sensory function, which otherwise would be totally nonfunctional. The most dramatic results were noted in those patients who underwent operations within 6 weeks of injury. The results of these procedures offer patients a valid therapeutic modality for an enhanced quality of life after cervical nerve root avulsion.

Adult↗

PubMed1993

Spondylectomy, microsurgical decompression and osteosynthesis in the treatment of complex disorders of the cervical spine.

In 44 patients with complex degenerative, traumatic, neoplastic and infectious disorders of the cervical spine an aggressive surgical approach was used, consisting of spondylectomy, radical microsurgical decompression and osteosynthesis. The patient group consisted of 23 patients with multisegmental cervical spondylosis, 9 patients with primary or metastatic malignant tumour disease spread along the cervical spine, 6 patients with complex cervical trauma and 6 patients with infection affecting one or more cervical segments. Considering the heterogeneity of the group of patients treated, a multitude of neurological symptoms and signs were present. Excruciating pain was the predominant symptom in 84% of the patients, followed by sensory and motor signs of varying degrees in 77% and 65% respectively. Involvement of the long tracts was present in 51%, gait disturbance in 49% and bladder disfunction in 28%. Considering the nature of the underlying disease, in the group with multisegmental cervical spondylosis (MSCS), advanced cervical myelopathy was the predominant clinical symptom, whereas in those patients with trauma, tumour or infection, pain was the leading symptom, followed by disturbed motor and/or sensory function. Altogether 59 vertebrae have been removed in the 44 patients. In 28 patients spondylectomy was performed at one level, in 15 patients at two levels and in one female tumour patient at three levels. In 34 patients an iliac crest bone graft was used and in 10 patients bone cement. Within the observation period, solid fusion was achieved in all patients. In one tumour patient screw loosening was demonstrable at follow-up, but the fusion remained stable. 2 patients with infectious disease required re-operation due to significant loosening of screws and plates. However, after re-stabilization solid fusion was achieved. Considering amelioration of specific pre-operative symptoms and signs, excruciating pain responded best to the stabilizing procedure, with improvement in over 90% of the patients, followed by improvement of sensory and motor deficits in 85% and 82% respectively. Improvement in pre-operative gait disturbance could be achieved in 81% of the patients, while disturbance of bladder function is less likely to improve after surgery with a positive response in only 58%. None of the patients became neurologically worse after surgery. With regard to the underlying disease, patients with MSCS and tumour had the best results with overall improvement in 62% and 75% respectively. While in patients with infection improvement could be achieved in 58%, improvement in trauma patients was demonstrable in only 34% while in 66% the pre-operative clinical status remained unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1995

The sensory-motor role of growth cone filopodia.

Neuronal growth cones, the motile tips of elongating axons and dendrites, respond very precisely to cues encountered during pathfinding. During the past year, our knowledge about their sensory function, their integrative properties, and their motor function has advanced significantly. In particular, growth cone filopodia are currently being recognized for their prominent roles as sensors, transducers, and autonomous motor structures important for growth cone steering.

Animals↗

PubMed1992

Effects of stimulation intensity, gender and handedness upon auditory evoked potentials.

Left handers and women show less anatomical brain asymmetry, larger corpus callosum and more bilateral representation of specific functions. Sensory and cognitive components of cortical auditory evoked potentials (AEP) have been shown to be asymmetric in right handed males and to be influenced by stimulus intensity. In this study the influence of sex, handedness and stimulus intensity upon AEP components is investigated under basal conditions of passive attention. 14 right handed males, 14 right handed females, 14 left handed males, and 14 left handed females were studied while lying awake and paying passive attention to auditory stimulation (series of 100 binaural clicks, duration 1 msec, rate 1/sec, at four intensities). Cz, C3 and C4 referenced to linked mastoids and right EOG were recorded. Analysis time was 400 msec, average evoked potentials were based on 100 clicks. Stimulus intensity and gender affect early sensory components (P1N1 and N1P2) at central leads, asymmetry is influenced only by handedness, right handers showing larger P1N1 amplitudes over the right hemisphere.

Acoustic Stimulation↗

PubMed2004

Sexual responsiveness in women with spinal cord injuries: differential effects of anxiety-eliciting stimulation.

Sexual dysfunction is a common problem in women after spinal cord injuries (SCIs). Recently, the use of anxiety-provoking stimulation has been explored as a means of improving sexual responses in able-bodied sexually functional and dysfunctional women. In this laboratory-based study, we assessed the sexual and autonomic responses of women with SCIs with varying degrees of preservation of sympathetic innervation to their genitals to respond to anxiety-provoking audiovisual (AV) stimulation. Subjects were 45 women with SCIs and 11 able-bodied women. For purposes of analysis, SCI subjects were grouped on the basis of the degree of preservation of sensation in the T11-L2 dermatomes. Results revealed that women with low sensory scores in these dermatomes achieved higher vaginal pulse amplitude (VPA) responses to audiovisual erotic stimulation after anxiety preexposure than after neutral preexposure; however, women with SCIs and the greatest degree of preservation of sensory function in the T11-L2 dermatomes, as well as able-bodied controls, did not. Moreover, these same 2 groups of subjects had a decrease in VPA responses during baseline periods in which an anxiety-provoking video sequence was shown, but not during the neutral sequence. It is concluded that these findings are due to the proximity of sensory and autonomic neurologic elements in the spinal cord. Moreover, they demonstrate the differential effects of sympathetic stimulation on genital sexual arousal.

Adult↗

PubMed1995

Morbidity of the infraorbital nerve following orbitozygomatic complex fractures.

Acute sensory disturbances in the distribution of the infraorbital nerve are recognised signs present in patients with orbitozygomatic complex fractures. Fifty consecutive patients with unilateral orbitozygomatic complex fractures were evaluated with regard to the long-term infraorbital nerve sensory function. The highest incidence of long-term neurosensory deficits occurred in fractures with an undistracted frontozygomatic suture. This is in complete agreement with the distribution of long-term neurosensory deficits regarding the method of treatment for orbitozygomatic complex fractures. In our series slightly more than one-third of the patients had third or fourth degree nerve injuries, according to Sunderland's classification, to the infraorbital nerve following orbitozygomatic complex fractures. This outcome should influence the management of orbitozygomatic complex fractures. With regard to fixation of unstable malar fractures in relation to sensory recovery of the infraorbital nerve, miniplate osteosynthesis is recommended as opposed to wire fixation in all unstable bone fractures when there is displacement. Furthermore, open reduction and fixation of an orbitozygomatic complex fracture offer a better prognosis for complete recovery of the infraorbital nerve function than elevation only with or without Kirschner wire fixation.

Adult↗

PubMed1986

Recovery of function after neonatal or adult hemispherectomy in cats: I. Time course, movement, posture and sensorimotor tests.

Cats with removal of the left hemitelencephalon (hemispherectomy) as neonates (n = 12) or in adulthood (n = 14), were compared using a battery of 16 neurological and behavioral tests given when they were young adults (kittens) or at least 5 months after the lesion (adults). The neonatal-lesioned subjects grew normally and performed markedly and significantly better than adult-lesioned cats in 13 tests covering the wide range of movement, posture and sensory functions which were assessed. None of the animals recovered tactile placing of the right forelimb or a normal vision in the right visual field. However, the overall recovery was outstanding for all cats such that the neonatal-lesioned were hard to differentiate from intact controls in their spontaneous, daily activities. Because the lesions were similar in the two age-at-lesion groups, and since numerous functions were followed for prolonged, comparable postlesion time, we conclude that, after hemispherectomy in the cat, there definitely is greater functional recovery if the lesion is sustained early in life. We propose that the enhanced recovery of function in neonatal-lesioned cats is largely due to the extensive anatomical reorganization which we have demonstrated in ongoing studies, and which contrasts with a lesser remodeling in adult-lesioned cats.

Age Factors↗