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BACKGROUND AND PURPOSE: Weakness is a significant impairment in persons with post-stroke hemiparesis, yet traditional clinical perspectives caution against strengthening in neurological populations. Significant correlations between weakness and functional movement have been demonstrated, however, a clear relationship between increased strength and functional improvement has been elusive. This case study describes a combined program of dynamic, high-intensity resistance training and functional task practice for the upper-extremity in adult hemiparesis. CASE DESCRIPTION: The patient was a 65-year-old, right hand dominant woman who presented to the Neural Control of Movement Laboratory at the Palo Alto VA Rehabilitation Research and Development Center 16 weeks following clipping of an unruptured aneurysm with consequent dense right hemiparesis. She received 7 weeks of acute rehabilitation according to CARF guidelines (ie, at least 3 hours of two or more disciplines, 6 days per week). Her baseline research evaluation revealed significant upperextremity deficits at the ICF body structure/function level including: weakness, shoulder pain, mild resistance to passive movement, and need for moderate to maximal assistance in many activities of daily living including bathing and dressing. The Stroke Impact Scale score reporting her perspective indicated she had recovered from her stroke only 50%. The hybrid resistance training-functional task practice intervention, detailed in this report, was delivered 3 times per week for 6 weeks with each session lasting 75:00. OUTCOMES: The subject revealed marked improvements in isometric and dynamic force production in 5 key upper-extremity actions: elbow flexion, elbow extension, shoulder flexion, shoulder abduction, and shoulder external rotation. Strength gains were accompanied by increased EMG activation immediately postintervention and by a combination of increased activation and apparent hypertrophic effects at 6 month follow up. Marked improvements were noted in all clinical and functional measures and in an elbow trajectorytracking task which served as a surrogate measure of motor control. DISCUSSION: Improvements in strength and positive outcome effects at the physiological, clinical, and functional levels were observed in this subject following the experimental hybrid upper-extremity rehabilitation intervention described. Importantly, no deleterious effects were observed including exacerbation of spasticity or musculoskeletal compromise. Observations of improved EMG activation in this case study suggest that improvements in motor activation underlie these strength gains and can likely be attributed to working at a high intensity level.
Motoric and evacuatory function of gastric stump were studied with bengal rose 131I in 47 patients who had undergone stomach resection for peptic ulcer in remote post-operative period with the view to study functional peculiarities of different gastroenteroanastomosis. The results evidenced in favour of Bilroth I stomach resection with retained passage of duodenal content. Bilroth II stomach resection followed by anastomosis put with cross dissection of intestinal wall was noted to preserve physiological evacuation of gastric content into intestine, which indicates its superiority to conventional Hofmeister-Finsterer's method.
Cholinergic neurotransmission supports motor, autonomic, and cognitive function and is compromised in myasthenias, cardiovascular diseases, and neurodegenerative disorders. Presynaptic uptake of choline via the sodium-dependent, hemicholinium-3-sensitive choline transporter (CHT) is believed to sustain acetylcholine (ACh) synthesis and release. Analysis of this hypothesis in vivo is limited in mammals because of the toxicity of CHT antagonists and the early postnatal lethality of CHT-/- mice (Ferguson et al., 2004). In Caenorhabditis elegans, in which cholinergic signaling supports motor activity and mutant alleles impacting ACh secretion and response can be propagated, we investigated the contribution of CHT (CHO-1) to facets of cholinergic neurobiology. Using the cho-1 promoter to drive expression of a translational, green fluorescent protein-CHO-1 fusion (CHO-1:GFP) in wild-type and kinesin (unc-104) mutant backgrounds, we establish in the living nematode that the transporter localizes to cholinergic synapses, and likely traffics on synaptic vesicles. Using embryonic primary cultures, we demonstrate that CHO-1 mediates hemicholinium-3-sensitive, high-affinity choline uptake that can be enhanced with depolarization in a Ca(2+)-dependent manner supporting ACh synthesis. Although homozygous cho-1 null mutants are viable, they possess 40% less ACh than wild-type animals and display stress-dependent defects in motor activity. In a choline-free liquid environment, cho-1 mutants demonstrate premature paralysis relative to wild-type animals. Our findings establish a requirement for presynaptic choline transport activity in vivo in a model amenable to a genetic dissection of CHO-1 regulation.
Tolcapone is a potent catechol-O-methyltransferase inhibitor that prolongs the plasma half-life of levodopa. This multicenter, double-blind, placebo-controlled study used two 10-hour clinical evaluations to compare the efficacy and safety of three doses of tolcapone (50, 200, and 400 mg tid) with placebo in patients with Parkinson's disease (PD) experiencing motor fluctuations from levodopa/carbidopa. One hundred fifty-one patients completed the study. Clinical evaluations lasting 10 hours were performed on day -1 and day 42 using United Parkinson's Disease Rating Scale motor subscale and "on/off" and dyskinesia assessments every 30 minutes. Tolcapone significantly reduced "off" time an average of 40% and increased total "on" time by about 25% at all dose levels, as compared to placebo treatment. Levodopa/carbidopa dosage and frequency were significantly reduced. Tolcapone was well tolerated, with patients experiencing typical dopaminergic side effects that could be reduced or eliminated by lowering levodopa/carbidopa dosages. Tolcapone was effective at prolonging the clinical benefit of levodopa and reducing total levodopa requirements in PD patients with motor fluctuations.
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Tests of visual, vestibular, sensori-motor and balance function were administered to 550 women, aged between 20 and 99 years at a Balance and Gait Laboratory. All of the sensory, motor and balance system measures showed significant age-associated differences. Multiple regression analyses revealed that the measures of lower limb sensation were the consistent sensori-motor factors contributing to balance under normal conditions (standing on a firm surface with eyes open or closed). Under more challenging conditions (standing on foam with eyes open) vision, strength and reaction time played significant roles, whilst when standing on foam with eyes closed, vestibular function also made a significant contribution. Analysis of percentage increases in sway under conditions where visual and peripheral sensation systems were removed or diminished, compared with sway under optimal conditions, indicated that up until age 65 there was an increased reliance on vision for balance control. Beyond this age, the contribution made by vision declined, so that in the oldest age-groups reduced vision was less able to supplement peripheral input, resulting in increased sway areas. Peripheral sensation however was the most important sensory system in the maintenance of static postural stability at all ages.
In many recovering hemiparetic stroke patients, movement of the affected limb elicits ipsilateral activation of sensorimotor areas within the undamaged hemisphere, which is not observed in control subjects. Following middle cerebral artery occlusion, rats received intensive enriched-rehabilitation (ER) of the impaired forelimb for 4 weeks. Weekly assessments on a skilled reaching test demonstrated significant improvement in ischemic animals over 4 weeks of ER (P < 0.05). We hypothesized that if the undamaged forelimb motor cortex contributed to improved forelimb function, then inhibition of neural activity within this region should reinstate (at least some of) the initial motor impairment. After 3 and 4 weeks of ER, animals received a microinjection of lidocaine hydrochloride into the undamaged motor cortex and were re-assessed on reaching ability. The behavioral effect of lidocaine challenge was dependent on the size of the infarct: animals with large infarcts were rendered unable to retrieve any food pellets and had great difficulty even contacting a pellet with the affected forepaw. Small-infarct animals were only moderately affected (25% reduction in success) by lidocaine, an effect similar to that observed in control animals. Qualitative assessments of recovered reaching after 4 weeks of rehabilitation revealed that impairments in forelimb lift, advance and aim were exacerbated (P < 0.05) following lidocaine-inactivation of the undamaged motor cortex of animals with large ischemic infarcts. In animals with small infarcts, lidocaine challenge only impaired limb advance. Thus, recruitment of the undamaged hemisphere may depend on the functional integrity of the remaining sensorimotor system. These data suggest that, in the rat, the undamaged (ipsilateral) motor system may contribute to compensatory recovery of the affected forelimb.
OBJECTIVES: Even in the days of modern microsurgery, the removal of a brain stem lesion remains a surgical challenge. Especially when operating on children, the prognosis is directly related to the radicality of the resection; however, a radical resection is often associated with surgical morbidity. Intraoperative neuromonitoring could help to minimise the surgical morbidity, but few studies have been performed to clarify the value of this monitoring. We investigated a prospective series of 21 patients with lesions involving the brain stem for the prognostic value and benefits of neuromonitoring. METHODS: We performed intraoperative neuromonitoring of cranial nerve function by electromyography (EMG) and motor evoked potential (MEP). The results were correlated with postoperative neurological deficits. CONCLUSIONS: There is a good correlation between intraoperative neurophysiological events and postoperative neurological deficits in patients with lesions of the brain stem. In general, transient, prolonged, spontaneous activity in EMG is associated with a transient paresis of the respective muscle, whereas a permanent spontaneous activity is associated with a permanent deficit. Intraoperative neuromonitoring reliably predicts postoperative neurological function in patients with tumours of the lower brain stem and fourth ventricle. This neuromonitoring guides the neurosurgeon in the operation and may decrease surgical morbidity. We recommend using monitoring of MEP and EMG of the lower cranial nerves in surgery on all patients with lesions involving the lower brain stem and fourth ventricle.
The actin-based motor protein myosin II plays a critical role in many cellular processes in both muscle and non-muscle cells. Targeted disruption of the Dictyostelium regulatory light chain (RLC) caused defects in cytokinesis and multicellular morphogenesis. In contrast, a myosin heavy chain mutant lacking the RLC binding site, and therefore bound RLC, showed normal cytokinesis and development. One interpretation of these apparently contradictory results is that the phenotypic defects in the RLC null mutant results from mislocalization of myosin caused by aggregation of RLC null myosin. To distinguish this from the alternative explanation that the RLC can directly influence myosin activity, we expressed three RLC point mutations (E12T, G18K and N94A) in a Dictyostelium RLC null mutant. The position of these mutations corresponds to the position of mutations that have been shown to result in familial hypertrophic cardiomyopathy in humans. Analysis of purified Dictyostelium myosin showed that while these mutations did not affect binding of the RLC to the MHC, its phosphorylation by myosin light chain kinase or regulation of its activity by phosphorylation, they resulted in decreased myosin function. All three mutants showed impaired cytokinesis in suspension, and one produced defective fruiting bodies with short stalks and decreased spore formation. The abnormal myosin localization seen in the RLC null mutant was restored to wild-type localization by expression of all three RLC mutants. Although two of the mutant myosins had wild-type actin-activated ATPase, they produced in vitro motility rates half that of wild type. N94A myosin showed a fivefold decrease in actin-ATPase and a similar decrease in the rate at which it moved actin in vitro. These results indicate that the RLC can play a direct role in determining the force transmission and kinetic properties of myosin.
OBJECTIVE: The objective of the study was to determine the effects of short-term levodopa administration on motor, cognitive, and psychiatric aspects of Parkinson's disease (PD). BACKGROUND: The effects of levodopa on mental processes in PD are controversial. Opinions range from the claim that levodopa improves cognition to the opposite view that levodopa causes or exacerbates dementia, delusions, and hallucinations. Of the 800 idiopathic PD patients enrolled in the original DATATOP study, 387 reached the end point of functional disabilities sufficiently severe to require levodopa treatment. There were 263 men and 124 women who were comparable with regard to age, symptom duration of PD, and measures of PD severity. We compared test scores on motor performance, cognitive function, and psychiatric status before levodopa and again within 6 months after initiation of levodopa therapy. RESULTS: Levodopa administration improved all motor functions significantly. The improvement was significantly greater in women than in men. Levodopa administration did not worsen scores on any cognitive tests, and there were quantitatively small but significant improvements in tests of frontal lobe function. Levodopa exerted only minor effects on psychiatric measures. There were small but significant decreases in scores for depression, and increases in vivid dreams and hallucinations. CONCLUSIONS: Levodopa administration for up to 6 months in dosages sufficient to improve motor function has only small effects on cognitive function and psychiatric status in mild to moderate PD patients. We conclude that motor symptoms in early PD, which result from dopamine depletion, are dissociable from cognitive functions and psychiatric status, which may be more dependent on nondopaminergic mechanisms.
In the present investigation, the vasoconstrictive, motor and neurodegenerative effects of intrathecal somatostatin (SST) were assessed in guinea pigs implanted with lumbar intrathecal catheters. Five consecutive dose increments of SST (5, 10, 15, 30 and 60 micrograms) to a total of 120 micrograms during the period of 16 +/- 3 min, resulted in a moderate (< 20%), gradual decrease of the spinal blood flow monitored with the laser-doppler method. A subsequent injection of clonidine (50 micrograms) or norepinephrine (10 micrograms) resulted in a more pronounced decrease of spinal blood flow (35% and 79%, respectively). Three consecutive, daily intrathecal injections of 30 or 60 micrograms SST did not cause any loss of weight support or paralysis of the hind limbs. There were no histopathological changes in the white or gray matter of the thoracic and lumbar sections of the spinal cords. It is concluded that SST, in the doses studied, is not neurodegenerative in guinea pigs. These findings are in contrast to those previously seen in rats. The implication of this study may be the necessity to use several alternate animal species in order to evaluate the antinociceptive and neurodegenerative properties of the peptides administered by the intrathecal route and the choice of dose to be compared across species.
We examined the prevalence and correlates of anomalous motor speed asymmetry in 104 right-handed patients with a diagnosis of probable Alzheimer's disease (AD). On the Halstead-Reitan Finger Tapping Test, over 60% of the AD patients exhibited notable departures from expected finger tapping asymmetry; 26% displayed an exaggerated right hand tapping advantage (ASYM RIGHT patients) and 37% showed a reversal of expected asymmetry (left hand speed equal to or greater than right hand speed, ASYM LEFT patients). ASYM-RIGHT patients had significantly more years of education than the ASYM-LEFT patients, suggesting that these patients had higher premorbid verbal abilities and possibly had a left hemisphere that was relatively resilient to the effects of AD. Motor speed asymmetry was correlated significantly with cognitive asymmetries (e.g., Verbal IQ vs. Performance IQ, naming vs. figure copying). Finally, ASYM-RIGHT patients exhibited a lower incidence of hallucinations and apathy than ASYM-LEFT patients or patients with normal motor asymmetry.
In chronic experiments on dogs, preliminary stimulation of corticomedial and parvocellular basal nuclei of amygdala augmented the motor responses of the gastro-intestinal tract to subsequent stimulation of median hypothalamic structures and weakened the inhibitory effects of posterior hypothalamic structures on motility of the digestive tract. After preliminary stimulation of the hypothalamus, the motor responses of stomach and small intestine to subsequent stimulation of corticomedial and parvocellular basal nuclei of amygdala were enhanced. The data obtained suggest existence of a complex functional hypothalamo-amygdaloid interaction, the hypothalamus with its basic mechanisms of regulation of motor function of the digestive tract playing the leading part in this interaction.
Our previous work showed that repeated exposure to methyl parathion (MP) caused a prolonged inhibition of acetylcholinesterase (AChE) activity (approximately 80%) and down-regulation of M(1) and M(2) muscarinic receptors (up to 38%) in rats at brain regions, including frontal cortex, striatum, hippocampus and thalamus. In the present neurobehavioral study, we found this repeated MP treatment had suppressant effects on rat's locomotor activity. However, we observed no evidence of long-term effects of MP on associative learning and memory. Our data demonstrated that repeated exposure to MP caused some functional deficits in CNS, but motor activity and associative learning/memory process might differ in the sensitivity to its toxic effect. The motor dysfunctions in MP-treated rats may be mediated via reciprocal balance between cholinergic and dopaminergic systems at striatum following cholinergic over-stimulation. Our findings also suggest that the CNS deficits induced by repeated exposure to MP or other organophosphate (OP) pesticides cannot be attributed entirely to the inhibition of AChE. To accurately assess the neuro-toxic risk by occupational exposure to sub-lethal doses of MP, novel biomarkers besides in vivo anticholinesterase potency are needed.
82% of cats revealed natural domineering of forelimbs forming in early ontogenesis movements of different degrees of complexness in conditions of equal input signals so both hemispheres. Among these animals 75% appeared to be "right-pawed". This phenomenon points out an initial, apparently hereditary interhemisphere asymmetry of functional state of the brain motor structures.
Huntington's disease (HD) is an inherited disorder characterized by cognitive impairments, motor deficits, and progressive dementia. These symptoms result from progressive neurodegenerative changes mainly affecting the neostriatum. This pathology is fatal in 10 to 20 years and there is currently no treatment for HD. Early in the course of the disease, initial clinical manifestations are due to striatal neuronal dysfunction, which is later followed by massive neuronal death. A major therapeutic objective is therefore to reverse striatal dysfunction prior to cell death. Using a primate model reproducing the clinical features and the progressive neuronal degeneration typical of HD, we tested the therapeutic effects of direct intrastriatal infusion of ciliary neurotrophic factor (CNTF). To achieve a continuous delivery of CNTF over the full period of evaluation, we took advantage of the macroencapsulation technique. Baby hamster kidney (BHK) cells previously engineered to produce human CNTF were encapsulated into semipermeable membranes and implanted bilaterally into striata. We show here that intracerebral delivery of low doses of CNTF at the onset of symptoms not only protects neurons from degeneration but also restores neostriatal functions. CNTF-treated primates recovered, in particular, cognitive and motor functions dependent on the anatomofunctional integrity of frontostriatal pathways that were distinctively altered in this HD model. These results support the hypothesis that CNTF infusion into the striatum of HD patients not only could block the degeneration of neurons but also alleviated motor and cognitive symptoms associated with persistent neuronal dysfunction.