Home About us Contact
|
Home About us Contact | ||
|
|
||
Motor Deficits (motor + deficit)
Selected AbstractsAltered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2004Julien Amendola Abstract Most neurodegenerative diseases become manifest at an adult age but abnormalities or pathological symptoms appear earlier. It is important to identify the initial mechanisms underlying such progressive neurodegenerative disease in both humans and animals. Transgenic mice expressing the familial amyotrophic lateral sclerosis (ALS)-linked mutation (G85R) in the enzyme superoxide dismutase 1 (SOD1) develop motor neuron disease at 8,10 months of age. We address the question of whether the mutation has an early impact on spinal motor networks in postnatal mutant mice. Behavioural tests showed a significant delay in righting and hind-paw grasping responses in mutant SOD1G85R mice during the first postnatal week, suggesting a transient motor deficit compared to wild-type mice. In addition, extracellular recordings from spinal ventral roots in an in vitro brainstem,spinal cord preparation demonstrated different pharmacologically induced motor activities between the two strains. Rhythmic motor activity was difficult to evoke with N -methyl- dl -aspartate and serotonin at the lumbar levels in SOD1G85R mice. In contrast to lumbar segments, rhythmic activity was similar in the sacral roots from the two strains. These results strongly support the fact that the G85R mutation may have altered lumbar spinal motor systems much earlier than previously recognized. [source] Evaluation of simple and complex sensorimotor behaviours in rats with a partial lesion of the dopaminergic nigrostriatal systemEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2000Pascal Barnéoud Abstract We have examined the behavioural consequences of a partial unilateral dopaminergic denervation of the rat striatum. This partial lesion was obtained by an intrastriatal 6-hydroxy-dopamine injection (6-OHDA, 20 or 10 ,g divided between two injection sites) and was compared with a unilateral complete lesion resulting from an injection of 6-OHDA (2 × 6 ,g) into the medial forebrain bundle. Quantification of striatal dopamine (DA) and its metabolites, and the immunohistochemical evaluation of the nigrostriatal DA system confirmed the complete and partial lesions. Animals with complete striatal denervation displayed both apomorphine- and amphetamine-induced rotations whereas the partial denervation elicited amphetamine-induced rotations only. However, the rates of amphetamine-induced rotation were not correlated with the size of the lesion. In contrast, the paw-reaching impairments were significantly correlated with the striatal dopaminergic depletion. When evaluated in the staircase test, animals with partial denervation were impaired exclusively for the paw contralateral to the side of the lesion. This motor deficit (50,75%) included all components of the skilled paw use (i.e. attempt, motor coordination and success) and was observed at least 12 weeks after the lesion. However, these animals were able to perform normal stepping adjustments with the impaired paw, indicating that the partial lesion induced a coordination deficit of the paw rather than a deficit of movement initiation. After a complete lesion, stepping adjustments of the contralateral paw were dramatically impaired (by 80%), an akinesia which almost certainly accounted for the great deficit in skilled paw use. The paw-reaching impairments resulting from the partial striatal denervation are proposed as a model of the early symptoms of Parkinson's disease and may be useful for the development of restorative therapies. [source] Deficiency of electroneutral K+,Cl, cotransporter 3 causes a disruption in impulse propagation along peripheral nervesGLIA, Issue 13 2010Yuan-Ting Sun Abstract Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K+,Cl, cotransporter (KCC) family includes four isoforms (KCC1,4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K+ and Cl, with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2,4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na+,K+,2Cl, -cotransport inhibitor (bumetanide) dose-dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3,/, mice than in nerves from wild-type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild-type strains. KCC3,/, mice also manifested a prominent motor deficit in the beam-walking test. This is the first study to demonstrate that the K+,Cl, cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves. © 2010 Wiley-Liss, Inc. [source] Home alone: Assessing mobility independence before discharge,,§¶JOURNAL OF HOSPITAL MEDICINE, Issue 4 2009Dennis M. Manning MD, FACC Abstract Hospitalists are often confronted with discharge planning responsibility and decisions for elderly patients who live alone. The absence of an in-home helper (spouse, partner, or care-giver) reduces the margin of safety and resilience to any new debility. Research has documented that during hospital stays elderly patients tend to become deconditioned, even if there is no new specific neurologic or motor deficit. In the patient whose pre-hospital mobility independence is not robust, and perhaps marginally compensated, inpatient stays for any diagnosis may result in critical decrements in mobility independence. The present study is an effort to design a bedside tool for the hospitalist by which to discern, or screen, for such debility. The tool is a hierarchical performance test we named I-MOVE (Independent Mobility Validation Examination). It is a quick series of bedside mobility requests to demonstrate capability of fundamental movements critical to independent living. We describe manner in which I-MOVE can be performed. Moreover, we describe the face validity and the high interrater reliability (> 0.90 intra-class correlation coefficient) of two RNs who independently administered and scored I-MOVE for 41 patients on a General Medical Care Unit. Although not yet studied in correlation with outcomes, nor with validated mobility assessment tools, we believe I-MOVE can serve as a useful extension of the nurse's assessment, or the Hospitalist's physical examination. Discerning the continued capability of mobility independence is a desirable, on-going insight for discharge planning of the elderly patient who resides alone. Journal of Hospital Medicine 2009;4:252,254. © 2009 Society of Hospital Medicine. [source] Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple-system atrophy from progressive supranuclear palsyMOVEMENT DISORDERS, Issue 1 2007Dominic C. Paviour PhD, MRCP Abstract Progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple-system atrophy (MSA-P) may present with a similar phenotype. Magnetic resonance diffusion-weighted imaging (DWI) has been shown to be a sensitive discriminator of MSA-P from Parkinson's disease (PD). We studied 20 PSP, 11 MSA-P, 12 PD patients and 7 healthy controls in order to investigate whether regional apparent diffusion coefficients (rADCs) help distinguish PSP and MSA-P; whether rADCs are correlated with clinical disease severity scores; and the relationship between brainstem and cerebellar volumes and rADCs in PSP and MSA-P. The Unified Parkinson's Disease Rating Scale, Hoehn and Yahr score, Mini Mental State Examination, and frontal assessment battery were recorded in all patients. Regional ADCs were measured in the middle cerebellar peduncle (MCP), caudal and rostral pons, midbrain, decussating fibers of the superior cerebellar peduncle, thalamus, putamen, globus pallidus, caudate nucleus, corpus callosum, frontal and parietal white matter, as well as the centrum semiovale. In MSA-P, rADCs in the MCP and rostral pons were significantly greater than in PSP (P < 0.001 and 0.009) and PD (P < 0.001 and = 0.002). Stepwise logistic regression revealed that the MCP rADC distinguishes MSA-P from PSP with a sensitivity of 91% and a specificity of 84%. Increased brainstem rADCs were associated with motor deficit in MSA-P and PSP. Increased rADCs in the pons and MCP were associated with smaller pontine and cerebellar volumes in MSA-P. rADCs distinguish MSA-P from PSP. These have a clinical correlate and are associated with reduced brainstem and cerebellar volumes. © 2006 Movement Disorder Society [source] Two-year follow-up results after treatment of lumbar instability with titanium-coated fusion systemORTHOPAEDIC SURGERY, Issue 2 2009Ya-feng Zhang MD Objective:, The purpose of this prospective clinical trial, with a minimum two-year follow-up, was to evaluate the clinical effects of a titanium-coated lumbar interbody fusion system in the treatment of lumbar instability. Methods:, The study cohort consisted of 94 patients with lumbar instability who accepted posterior lumbar interbody fusion with a titanium-coated fusion system. The patients were examined at the sixth, 12th and 24th month postoperatively. The clinical outcomes of all patients were evaluated according to the Japanese Orthopaedic Association (JOA) score and Oswestry disability index (ODI). Radiological studies, which included assessment of loss of disc space height, intervertebral angle and isodense bone bridging, were used to evaluate the fusion. Results:,The overall fusion rate was 95.75% at the 24th month after surgery. Ninety-two (97.87%) patients were able to work while 53 patients (56.38%) were capable of performing heavy manual labor. Neurological assessment showed 77 patients (81.92%) had no sensory or motor deficit. The mean JOA score had increased from 15.34 to 28.92 and ODI had decreased from 45 to 15 at the 24th month after surgery. No implant fracture or displacement was found. Conclusion:, The titanium-coated intervertebral fusion cage is effective and safe for treatment of lumbar instability. [source] DICHOTOMY OF CORTICAL PAIN PROCESSINGPAIN MEDICINE, Issue 2 2002Article first published online: 4 JUL 200 Jahangir Maleki, Rollin M. Gallagher, Pain Medicine and Rehabilitation Center, MCP/Hahnemann School of Medicine Introduction: Functional MRI and PET studies of cortical pain processing indicate segregated pain pathways above the thalamus. Although experimental pain may result in multiple areas of altered cortical activity, it is postulated that thalamic pain fibers known as the lateral system, projecting to sensory cortex, serve to localize pain, whereas medial pathways projecting to limbic cortex, process affective aspects of pain. Case Study: A 27 y/o female, with left upper extremity pain and severe allodynia from Complex Regional Pain Syndrome, Type I (CRPS I / RSD), after receiving intra-pleural bupivacaine blocks developed an ipsilateral focal-onset secondary generalized tonic clonic seizure. This was followed by one hour of post-ictal confusion. Simultaneously she developed a dense left-sided motor and sensory deficit (Todd's palsy) with a motor deficit resolving in one day whereas a sensory deficit lasted 2 days. Throughout the duration of the sensory deficit she denied any left arm pain, although she continued to report the same intensity of pain, but now localized to her epigastric region. Interestingly, despite the lack of sensory perception on the left side, palpation of her left arm resulted in increased epigastric pain and suffering. Discussion: This case indicates a bifurcation of the pain pathway between the thalamus and cortex. Due to focal seizure activity, the sensory cortex (i.e. lateral system) was transiently rendered dysfunctional, during which time the continued presence of pain and allodynia without appropriate localization likely resulted from pain conduction, from the thalamus to functional limbic structures such as Cingulum (i.e. via the medial fibre system). Conclusion: This case report strongly supports the hypothesis of medial and lateral pain conducting fibers branching at the level of thalamus with medial sub-serving the emotional aspects of pain by projection to limbic cortex, whereas lateral fibres project to sensory cortex, primarily serving a localizing function. [source] Radiofrequency Treatment of Peripheral NervesPAIN PRACTICE, Issue 3 2002O.J.J.M. Rohof MD Neurolysis by surgical, chemical, cryogenic, or thermal means may be considered as an option on seldom occasions, because of the risk of neuritis and deafferentation pain, motor deficit, and potential unintentional damage to nontargeted tissue. To our knowledge, there is only 1 report concerning selective radiofrequency (RF) treatment of the obturator and femoral nerves that was published. The introduction of the non-neurodestructive pulsed radiofrequency technique has provided new possibilities for the treatment of peripheral nerves. Today there is some experience with the management of chronic shoulder pain and additional case reports on other indications. [source] Predicting motor recovery of the upper limb after stroke rehabilitation: value of a clinical examinationPHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 1 2000Hilde Feys Abstract Background and Purpose Only a few studies have been conducted to predict motor recovery of the arm after stroke. The aims of this study were to identify which clinical variables, assessed at different points in time, were predictive of motor recovery, and to construct useful regression equations. Method One hundred consecutive stroke patients who had an obvious motor deficit of the upper limb were evaluated on entry to the study (two to five weeks post-stroke) and at two, six and 12 months after stroke. The Brunnström,Fugl-Meyer test was used as the outcome measure. Predictors included demographic data, overall disability, clinical neurological features, neuropsychological factors and secondary shoulder complications. Results In multiple regression analyses, motor performance was invariably retained as the predictive factor with the highest R-square. Other significant predictive variables were overall disability, muscle tone, proprioception and hemi-inattention. Between 53% and 89% of the total amount of variance was accounted for in all selected models. The accuracy of prediction from clinical measurement in the acute phase diminished as the time span of measurement of outcome increased. Similarly, assessment of the variables at two and six months, rather than in the acute stage, resulted in a considerable improvement in the percentage variance explained at 12 months. The highest accuracy was obtained when predictions were made step-by-step in time. Conclusions It is possible to predict motor recovery of the upper limb accurately through the use of a few clinical measures. Predictive equations are proposed, the use of which are practicable in both clinical practice and research. Copyright © 2000 Whurr Publishers Ltd. [source] Shoulder Disability After Different Selective Neck Dissections (Levels II,IV Versus Levels II,V): A Comparative StudyTHE LARYNGOSCOPE, Issue 2 2005Johnny Cappiello MD Abstract Objectives/Hypothesis: The objective was to compare the results of clinical and electrophysiological investigations of shoulder function in patients affected by head and neck carcinoma treated with concomitant surgery on the primary and the neck with different selective neck dissections. Study Design: Retrospective study of 40 patients managed at the Department of Otolaryngology, University of Brescia (Brescia, Italy) between January 1999 and December 2001. Methods: Two groups of 20 patients each matched for gender and age were selected according to the type of neck dissection received: patients in group A had selective neck dissection involving clearance of levels II,IV, and patients in group B had clearance of levels II,V. The inclusion criteria were as follows: no preoperative signs of myopathy or neuropathy, no postoperative radiotherapy, and absence of locoregional recurrence. At least 1 year after surgery, patients underwent evaluation of shoulder function by means of a questionnaire, clinical inspection, strength and motion tests, electromyography of the upper trapezius and sternocleidomastoid muscles, and electroneurography of the spinal accessory nerve. Statistical comparisons of the clinical data were obtained using the contingency tables with Fisher's Exact test. Electrophysiological data were analyzed by means of Fisher's Exact test, and electromyography results by Kruskal-Wallis test. Results: A slight strength impairment of the upper limb, slight motor deficit of the shoulder, and shoulder pain were observed in 0%, 5%, and 15% of patients in group A and in 20%, 15%, and 15% of patients in group B, respectively. On inspection, in group B, shoulder droop, shoulder protraction, and scapular flaring were present in 30%, 15%, and 5% of patients, respectively. One patient (5%) in group A showed shoulder droop as the only significant finding. In group B, muscle strength and arm movement impairment were found in 25% of patients, 25% showed limited shoulder flexion, and 50% had abnormalities of shoulder abduction with contralateral head rotation. In contrast, only one patient (5%) in group A presented slight arm abduction impairment. Electromyographic abnormalities were less frequently found in group A than in group B (40% vs. 85% [P = .003]), and the distribution of abnormalities recorded in the upper trapezius muscle and sternocleidomastoid muscle was quite different: 20% and 40% in group A versus 85% and 45% in group B, respectively. Only one case of total upper trapezius muscle denervation was observed in group B. In both groups, electroneurographic data from the side of the neck treated showed a statistically significant increase in latency (P = .001) and decrease in amplitude (P = .008) compared with the contralateral side. There was no significant difference in electroneurographic data from the side with and the side without dissection in either group. Even though a high number of abnormalities was found on electrophysiological testing, only a limited number of patients, mostly in group B, displayed shoulder function disability affecting daily activities. Conclusion: The study data confirm that clearance of the posterior triangle of the neck increases shoulder morbidity. However, subclinical nerve impairment can be observed even after selective neck dissection (levels II,IV) if the submuscular recess is routinely dissected. [source] Multimodal microglia imaging of fiber tracts in acute subcortical stroke,ANNALS OF NEUROLOGY, Issue 6 2009Basia A. Radlinska BSc Objective Case series with 11C-PK11195 and positron emission tomography (PET) in stroke patients suggest that activated microglia may be detected in remote brain regions with fiber tract connections to the lesion site as an indicator of poststroke neuroinflammation. However, the specificity of these imaging findings remains to be demonstrated. Methods In a prospective controlled study, we measured microglia activity using 11C-PK11195-PET along the pyramidal tract, as defined by diffusion tensor imaging, in 21 patients with first-time acute subcortical ischemia within 2 weeks of stroke. Uptake ratios (affected vs unaffected side) were determined for a set of standardized volumes of interest along the pyramidal tracts (PT). Uptake ratios from patients in whom the PT was affected were compared with those in whom the PT was not affected. Uptake ratios were related to motor deficit and lesion size according to correlation analyses. Results Increased uptake ratios were only found in patients in whom the PT was affected by stroke. In the affected hemisphere, uptake was increased at the level of pons, midbrain, and internal capsule, but not in the oval center. The extent of remote microglia activation was independent of infarct size or clinical measures of stroke severity. Interpretation A specific activation of microglia was only found in patients in whom the PT was affected by the stroke and only caudal (anterograde) to the lesion; no activation was found in the retrograde direction or in those patients in whom the PT was not affected. These findings were independent of infarct size and may represent changes secondary to early Wallerian degeneration. Ann Neurol 2009;66:825,832 [source] A novel diketopiperazine improves functional recovery given after the onset of 6-OHDA-induced motor deficit in ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2009RVM Krishnamurthi Background and purpose:, Cyclo-L-glycyl-L-2-allylproline (NNZ-2591), a modified diketopiperazine, is neuroprotective and improves long-term function after hypoxic-ischaemic brain injury in rats. The present studies were designed to examine both the neuroprotective and neurotrophic actions of NNZ-2591 on neurochemical and behavioural changes in a rat model of Parkinson's disease. Experimental approach:, To examine its protective effect, either NNZ-2591 (20 ng·day,1) or saline was given intracerebroventricularly for 3 days starting 2 h after 6-hydroxydopamine (6-OHDA) induced unilateral striatal lesion. In a subsequent experiment either NNZ-2591 (0.2, 1 and 5 mg·day,1, s.c.) or saline was administered daily for 14 days starting 2 weeks after the lesion. Behavioural and neurochemical outcomes were examined using the adjusting step test and immunohistochemical staining. Key results:, Cyclo-L-glycyl-L-2-allylproline given 2 h after the lesion reduced the degree of motor deficit compared with the saline-treated group. Delayed treatment with NNZ-2591, initiated after the onset of motor deficit, significantly improved motor function from week 7 onwards compared with the saline-treated group. Neither treatment regime altered nigrostriatal dopamine depletion. NNZ-2591 significantly enhanced the expression of doublecortin-positive neuroblasts in the sub-ventricular zone. Conclusions and implications:, These studies reveal that early treatment with NNZ-2591 protects against the motor deficit induced by 6-OHDA and that treatment initiated after the establishment of motor impairment significantly improves long-term motor function. These effects of NNZ-2591 on functional recovery were independent of dopamine depletion and also appeared not to be symptomatic as the improved motor function was long-lasting. NNZ-2591 has potential as a therapeutic agent for neurodegenerative disorders. Mandarin translation of abstract [source] Spondylodiscitis due to Propionibacterium acnes: report of twenty-nine cases and a review of the literatureCLINICAL MICROBIOLOGY AND INFECTION, Issue 4 2010I. Uçkay Clin Microbiol Infect 2010; 16: 353,358 Abstract Propionibacterium acnes is the most frequent anaerobic pathogen found in spondylodiscitis. A documented case required microbiological proof of P. acnes with clinical and radiological confirmation of inflammation in a localized region of the spine. Microbiological samplings were obtained by surgery or aspiration under radiological control. Twelve males and 17 females (median age, 42 years) with spondylodiscitis due to P. acnes were diagnosed within the last 15 years. Three patients were immunosuppressed. All patients reported back pain as the main symptom, and most were afebrile. Three patients had a peripheral neurological deficit, one a motor deficit, and two a sensory deficit attributable to the infection; and six patients had an epidural abscess. The most frequent risk factor was surgery, which was present in the history 28 of 29 (97%) patients. The mean delay between spinal surgery and onset of disease was 34 months, with a wide range of 0,156 months. Osteosynthesis material was present in twenty-two cases (76%). In 24 (83%) patients, additional surgery, such as débridement or spondylodesis, was performed. Previous osteosynthesis material was removed in 17 of the 22 (77%) patients where it was present. Total cure was reported in all patients, except one, after a mean duration of antibiotic therapy of 10.5 weeks (range, 2,28 weeks). In conclusion, spondylodiscitis due to P. acnes is an acute infection closely related to previous surgery. The most prominent clinical feature is pain, whereas fever is rare, and the prognosis is very good. [source] Lower-extremity selective voluntary motor control in patients with spastic cerebral palsy: increased distal motor impairmentDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 3 2010EILEEN G FOWLER Aim, Multiple impairments contribute to motor deficits in spastic cerebral palsy (CP). Selective voluntary motor control (SVMC), namely isolation of joint movement upon request, is important, but frequently overlooked. This study evaluated the proximal to distal distribution of SVMC impairment among lower extremity joints. Method, Using a recently developed tool, the Selective Control Assessment of the Lower Extremity (SCALE), we evaluated the SVMC of the hip, knee, ankle, subtalar joint, and toes in a cross-sectional, observational study of 47 participants with spastic, diplegic, hemiplegic, and quadriplegic CP (22 males, 25 females; mean age 11y 9mo, SD 4y 8mo; Gross Motor Function Classification System levels I,IV). Results, Statistically significant decreases in SCALE scores from hip to toes were found using the Page statistical test for trend (p<0.001). Statistically significant differences (p<0.05) were found between all joint pairs, except toes versus subtalar, toes versus ankle, and right ankle versus subtalar joints. Cross-tabulation of score frequencies for all pairs revealed that proximal joint scores were higher or equal to distal ones 81 to 100% of the time. Excluding toes versus subtalar joints, proximal scores exceeded distal ones 94 to 100% of the time. Interpretation, We confirmed increasing proximal to distal SVMC impairment, which may have implications for treatment and research. [source] Working memory, processing speed, and set-shifting in children with developmental coordination disorder and attention-deficit,hyperactivity disorderDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2007Jan P Piek BSc (Hons) PhD It has been suggested that the high levels of comorbidity between attention-deficit-hyperactivity disorder (ADHD) and developmental coordination disorder (DCD) may be attributed to a common underlying neurocognitive mechanism. This study assessed whether children with DCD and ADHD share deficits on tasks measuring working memory, set-shifting, and processing speed. A total of 195 children aged between 6 years 6 months and 14 years 1 month (mean 10y 4mo [SD 2y 2mo]) were included in this study. A control group (59 males, 79 females), a DCD group (12 males, six females), an ADHD-predominantly inattentive group (16 males, four females), and an ADHD-combined group (15 males, four females), were tested on three executive functioning tasks. Children with DCD were significantly slower on all tasks, supporting past evidence of a timing deficit in these children. With few exceptions, children with ADHD did not perform more poorly than control children. These findings demonstrate the importance of identifying children with motor deficits when examining tasks involving a timing component. [source] Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: An ontogenic studyEPILEPSIA, Issue 10 2008Andréy Mazarati Summary Purpose:, To examine antiepileptogenic and antiictogenic potential of retigabine (RTG) under conditions of rapid kindling epileptogenesis during different stages of development. Methods:, The experiments were performed in postnatal day 14 (P14), P21, and P35 male Wistar rats. After stereotaxic implantation of hippocampal stimulating and recording electrodes, the effects of RTG on baseline afterdischarge (AD) properties were studied. Next, the animals underwent rapid kindling (sixty 10 s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of seizures (kindling acquisition), and responses to test stimulations after kindling (retention) were compared between RTG and vehicle-treated rats. Additionally, the effects of RTG on the severity of seizures in previously kindled animals were examined. Results:, When administered intraperitoneally in doses that induced only mild, or no motor deficits, RTG significantly dampened brain excitability, evident as the increase of AD threshold and shortening of AD duration. During kindling, RTG delayed the development of focal seizures in P14 rats, and prevented the occurrence of full limbic seizures at all three ages. At P14 and P21, but not at P35, pretreatment with RTG prevented the establishment of kindling-induced enhanced seizure susceptibility. Administration of RTG to kindled animals decreased the severity of seizures induced by test stimulation. The effect was most prominent at P14. Discussion:, RTG exerted both antiepileptogenic and antiictogenic effects under conditions of rapid kindling model. These effects were apparent during postneonatal, early childhood, and adolescent stages of development. [source] Absence Epilepsy with Onset before Age Three Years: A Heterogeneous and Often Severe ConditionEPILEPSIA, Issue 7 2003Yves Chaix Summary: Purpose: The classification of epilepsies and epileptic syndromes recognizes three syndromes with typical absences [TA, i.e., childhood and juvenile absence epilepsies (CAE and JAE), and epilepsy with myoclonic absences (EMA), none of which is characterized by onset in early childhood]. Although several other forms of absence epilepsies have been described recently, none concerns infants and very young children, and little is known about the nosology and prognosis of early-onset absences. Methods: We retrospectively selected all cases with onset of absences as the only or major seizure type before age 3 years and ,2 years of follow-up among cases newly referred between 1986 and 2002. Neurospychological assessments (generally IQ measure), behavior patterns, and schooling situations were reviewed for each child. Results: We found 10 patients (7 F, 3 M). No child had sensory or motor deficits: neuroimaging was performed in nine and was normal in eight, with aspecfic findings in one. Only two could be characterized as CAE and EMA, respectively, both with seizure control and a good cognitive outcome. Among the remaining eight cases, four had a fairly homogeneous presentation with predominantly brief absences and clearly asymmetric interictal EEGs. All eight had neuropsychological and/or behavioral difficulties. Three had full seizure control, and five, persisting absences, with a follow-up ranging beetween 2 years 8 months to 9 years 4 months; only one child was older than 12 years. Conclusions: Great heterogeneity exists among absence epilepsies of early onset, which are rare conditions. Only a few patients can be categorized into well-known syndromes. The overall prognosis is poor. Early onset of absences is uncommon, and multicenter studies should help clarify the nosology and prognosis. [source] Embryonic striatal grafts restore bi-directional synaptic plasticity in a rodent model of Huntington's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2009David Mazzocchi-Jones Abstract Embryonic striatal grafts integrate with the host striatal circuitry, forming anatomically appropriate connections capable of influencing host behaviour. In addition, striatal grafts can influence host behaviour via a variety of non-specific, trophic and pharmacological mechanisms; however, direct evidence that recovery is dependent on circuit reconstruction is lacking. Recent studies suggest that striatal grafts alleviate simple motor deficits, and also that learning of complex motor skills and habits can also be restored. However, although the data suggest that such ,re-learning' requires integration of the graft into the host striatal circuitry, little evidence exists to demonstrate that such integration includes functional synaptic connections. Here we demonstrate that embryonic striatal grafts form functional connections with the host striatal circuitry, capable of restoring stable synaptic transmission, within an excitotoxic lesion model of Huntington's disease. Furthermore, such ,functional integration' of the striatal graft enables the expression of host,graft bi-directional synaptic plasticity, similar to the normal cortico-striatal circuit. These results indicate that striatal grafts express synaptic correlates of learning, and thereby provide direct evidence of functional neuronal circuit repair, an essential component of ,functional integration'. [source] A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosetsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Mahmoud M. Iravani Abstract Standard MPTP treatment regimens in primates result in >,85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)-positive cells, which occurred mainly in the calbindin-D28k -poor nigrosomes with a similar loss of TH-immunoreactivity (TH-ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH-ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH-ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L-DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD. [source] A role for Connexin43 during neurodevelopmentGLIA, Issue 7 2007Amy E. Wiencken-Barger Abstract Connexin43 (Cx43) is the predominant gap junction protein expressed in premitotic radial glial cells and mature astrocytes. It is thought to play a role in many aspects of brain development and physiology, including intercellular communication, the release of neuroactive substances, and neural and glial proliferation and migration. To investigate the role of Cx43 in brain physiology, we generated a conditional knockout (cKO) mouse expressing Cre recombinase driven by the human GFAP promoter and a floxed Cx43 gene. The removal of Cx43 from GFAP-expressing cells affects the behavior of the mice and the development of several brain structures; however, the severity of the phenotype varies depending on the mouse background. One mouse subline, hereafter termed Shuffler, exhibits cellular disorganization of the cortex, hippocampus, and cerebellum, accompanied by ataxia and motor deficits. The Shuffler cerebellum is most affected and displays altered distribution and lamination of glia and neurons suggestive of cell migration defects. In all Shuffler mice by postnatal day two (P2), the hippocampus, cortex, and cerebellum are smaller. Disorganization of the ventricular and subventricular zone of the cortex is also evident. Given that these are sites of early progenitor cell proliferation, we suspect production and migration of neural progenitors may be altered. In conclusion, neurodevelopment of Shuffler/Cx43 cKO mice is abnormal, and the observed cellular phenotype may explain behavioral disturbances seen in these animals as well as in humans carrying Cx43 mutations. © 2007 Wiley-Liss, Inc. [source] Quantitative and qualitative evaluation of neuromotor behaviour in children with a specific speech and language disorderINFANT AND CHILD DEVELOPMENT, Issue 1 2002Michele Noterdaeme Abstract Several studies have described problems in a wide area of motor functions in language impaired children. The purpose of this study was to identify the nature of the motor deficits in two subgroups of language impaired children. A standard neurological examination was performed on 18 children with an expressive language disorder and 21 children with a receptive language disorder. The motor performance of the language disordered children was compared with the motor performance of 23 normal children. The standard neurological examination allowed for a qualitative and quantitative assessment of five specific neurological subsystems. Handedness was determined for all children. The language impaired children had more motor problems than the control children on most neurological subsystems. There were few statistically significant differences between the two groups of language impaired children. An excess in left-handedness was established in the group of children with a receptive language disorder. There was a co-occurrence of verbal and non-verbal deficits in language impaired children. As these motor problems put an additional burden on the development of language impaired children, they should be diagnosed as early as possible. Copyright © 2002 John Wiley & Sons, Ltd. [source] Changes in blood flow velocity in the middle and anterior cerebral arteries evoked by walkingJOURNAL OF CLINICAL ULTRASOUND, Issue 3 2002Krassen Nedeltchev MD Abstract Purpose Transcranial Doppler sonography (TCD) is an established method for assessing changes in blood flow velocity (BFV) coupled to brain activity. Our objective was to investigate whether walking induces measurable changes in BFV in healthy subjects. Methods Changes in BFV in both middle cerebral arteries (MCAs) of 40 healthy adult subjects during walking on a treadmill were measured using bilateral TCD. In 8 of the 40 subjects, 1 anterior cerebral artery (ACA) was monitored simultaneously with the contralateral MCA. The percentage increase in BFV (BFVI%) compared with the baseline velocity (V0), the percentage decrease in BFV (BFVD%) compared with the V0, and the normalized ACA-MCA ratio were analyzed. Results The overall mean (± standard deviation [SD]) V0 was 59.9 ± 11.6 cm/second in the left MCA and 60.1 ± 12.9 cm/second in the right MCA. Women had higher V0 values than men had. Walking evoked an initial mean overall BFVI% in both left (8.4 ± 5.1%) and right MCAs (9.1 ± 5.1%), followed by a decrease to below baseline values in 38 of 40 subjects. A statistically significant increase of the normalized ACA-MCA ratio was measured, indicating that changes in BFV in the ACA territory were coupled to brain activation during walking. Conclusions The use of functional TCD showed different changes in BFV in the ACAs and MCAs during walking. This method may be an interesting tool for monitoring progress in patients with motor deficits of the legs, such as paresis. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 30:132,138, 2002; DOI 10.1002/jcu.10047 [source] Radiation-induced brain disorders in patients with pituitary tumoursJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2004A Bhansali Summary Radiation-induced brain disorders (RIBD) are uncommon and they are grave sequelae of conventional radiotherapy. In the present report, we describe the clinical spectrum of RIBD in 11 patients who received post-surgery conventional megavoltage irradiation for residual pituitary tumours. Of these 11 patients (nine men, two women), seven had been treated for non-functioning pituitary tumours and four for somatotropinomas. At the time of irradiation the age of these patients ranged from 30 to 59 years (mean, 39.4 ± 8.3; median, 36) with a follow-up period of 6,96 months (mean, 18.3 ± 26.4; median, 11). The dose of radiation ranged from 45 to 90 Gy (mean, 51.3 ± 13.4; median, 45), which was given in 15,30 fractions (mean, 18.6 ± 5.0; median, 15) with 2.8 ± 0.3 Gy (median, 3) per fraction. The biological effective dose calculated for late complications in these patients ranged from 78.7 to 180 Gy (mean, 99.1 ± 27.5; median, 90). The lag time between tumour irradiation and the onset of symptoms ranged from 6 to 168 months (mean, 46.3 ± 57.0; median, 57). The clinical spectrum of RIBD included new-onset visual abnormalities in five, cerebral radionecrosis in the form of altered sensorium in four, generalized seizures in four, cognitive dysfunction in five, dementia in three and motor deficits in two patients. Magnetic resonance imaging (MRI)/CT of the brain was suggestive of radionecrosis in eight, cerebral oedema in three, cerebral atrophy in two and second neoplasia in one patient. Associated hormone deficiencies at presentation were hypogonadism in eight, hypoadrenalism in six, hypothyroidism in four and diabetes insipidus in one patient. Autopsy in two patients showed primitive neuroectodermal tumour (PNET) and brainstem radionecrosis in one, and a cystic lesion in the left frontal lobe following radionecrosis in the other. We conclude that RIBD have distinctive but varying clinical and radiological presentations. Diabetes insipidus and PNET as a second neoplastic disorder in adults following pituitary irradiation have not been reported previously. [source] Elevated oxidative stress and sensorimotor deficits but normal cognition in mice that cannot synthesize ascorbic acidJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Fiona E. Harrison Abstract Oxidative stress is implicated in the cognitive deterioration associated with normal aging as well as neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. We investigated the effect of ascorbic acid (vitamin C) on oxidative stress, cognition, and motor abilities in mice null for gulono-,-lactone oxidase (Gulo). Gulo,/, mice are unable to synthesize ascorbic acid and depend on dietary ascorbic acid for survival. Gulo,/, mice were given supplements that provided them either with ascorbic acid levels equal to- or slightly higher than wild-type mice (Gulo-sufficient), or lower than physiological levels (Gulo-low) that were just enough to prevent scurvy. Ascorbic acid is a major anti-oxidant in mice and any reduction in ascorbic acid level is therefore likely to result in increased oxidative stress. Ascorbic acid levels in the brain and liver were higher in Gulo-sufficient mice than in Gulo-low mice. F4 -neuroprostanes were elevated in cortex and cerebellum in Gulo-low mice and in the cortex of Gulo-sufficient mice. All Gulo,/, mice were cognitively normal but had a strength and agility deficit that was worse in Gulo-low mice. This suggests that low levels of ascorbic acid and elevated oxidative stress as measured by F4 -neuroprostanes alone are insufficient to impair memory in the knockouts but may be responsible for the exacerbated motor deficits in Gulo-low mice, and ascorbic acid may have a vital role in maintaining motor abilities. [source] Neuroprotective effects of prior limb use in 6-hydroxydopamine-treated rats: possible role of GDNFJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Ann D. Cohen Abstract Unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) causes a loss of dopamine (DA) in the ipsilateral striatum and contralateral motor deficits. However, if a cast is placed on the ipsilateral limb during the first 7 days following 6-OHDA infusion, forcing the animal to use its contralateral limb, both the behavioral and neurochemical deficits are reduced. Here, we examine the effect of forced reliance on a forelimb during the 7 days prior to ipsilateral infusion of 6-OHDA on the deficits characteristic of this lesion model. Casted animals displayed no behavioral asymmetries as measured 14,28 days postlesion and a marked attenuation in the loss of striatal DA and its metabolites at 30 days. In addition, animals receiving a unilateral cast alone had an increase in glial cell-line derived neurotrophic factor (GDNF) protein in the striatum corresponding to the overused limb. GDNF increased within 1 day after the onset of casting, peaked at 3 days, and returned to baseline within 7 days. These results suggest that preinjury forced limb-use can prevent the behavioral and neurochemical deficits to the subsequent administration of 6-OHDA and that this may be due in part to neuroprotective effects of GDNF. [source] Timing of Thyroid Hormone Action in the Developing Brain: Clinical Observations and Experimental FindingsJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2004R. T. Zoeller Abstract The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congential hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions. [source] Loss of synaptophysin-positive boutons on lumbar motor neurons innervating the medial gastrocnemius muscle of the SOD1G93A G1H transgenic mouse model of ALSJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2005Da Wei Zang Abstract Amyotrophic lateral sclerosis (ALS) is a common form of motor neuron disease (MND) that involves both upper and lower nervous systems. In the SOD1G93A G1H transgenic mouse, a widely used animal model of human ALS, a significant pathology is linked to the degeneration of lower motor neurons in the lumbar spinal cord and brainstem. In the current study, the number of presynaptic boutons immunoreactive for synaptophysin was estimated on retrogradely labeled soma and proximal dendrites of , and , motor neurons innervating the medial gastrocnemius muscle. No changes were detected on both soma and proximal dendrites at postnatal day 60 (P60) of , and , motor neurons. By P90 and P120, however, , motor neuron soma had a reduction of 14 and 33% and a dendritic reduction of 19 and 36%, respectively. By P90 and P120, , motor neuron soma had a reduction of 17 and 41% and a dendritic reduction of 19 and 35%, respectively. This study shows that levels of afferent innervation significantly decreased on surviving , and , motor neurons that innervate the medial gastrocnemius muscle. This finding suggests that the loss of motor neurons and the decrease of synaptophysin in the remaining motor neurons could lead to functional motor deficits, which may contribute significantly to the progression of ALS/MND. © 2005 Wiley-Liss, Inc. [source] Analysis of the course of Parkinson's disease under dopaminergic therapy: Performance of "fast tapping" is not a suitable parameterMOVEMENT DISORDERS, Issue 3 2005Peter H. Kraus MD Abstract In addition to clinical rating scales, instrumental methods are employed frequently for assessment of performance or motor deficits in Parkinson's disease (PD). Many studies have analyzed such parameters in cross-sectional studies. We employed a battery of tests to investigate fine motor performance over a period of 4 years in 411 de novo parkinsonian patients from the Prado study. Specifically, tapping and pegboard testing ("plugging") were evaluated and performance on these tests compared with clinical ratings. Plugging scores correlated well with tapping scores and clinical rating at each assessment timepoint. Both tests also showed significant differences to healthy controls. Nevertheless "fast tapping" was found to be less impaired than was plugging in de novo patients. Over time, it was observed that plugging scores, but not tapping scores, exhibited changes that paralleled movements in clinical score. Plugging scores exhibited a marked response to dopaminergic therapy whereas fast tapping showed no therapeutic response. Fast tapping is certainly not suitable for assessment of bradykinesia or hypokinesia, and does not respond to dopaminergic therapy. © 2004 Movement Disorder Society [source] Effect of pulsatile administration of levodopa on dyskinesia induction in drug-naïve MPTP-treated common marmosets: Effect of dose, frequency of administration, and brain exposureMOVEMENT DISORDERS, Issue 5 2003Lance A. Smith MSc Abstract Levodopa (L -dopa) consistently primes basal ganglia for the appearance of dyskinesia in parkinsonian patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) -treated primates. This finding may reflect its relatively short duration of effects resulting in pulsatile stimulation of postsynaptic dopamine receptors in the striatum. We have compared the relationship between L -dopa dose and frequency of administration on dyskinesia initiation in drug-naïve, MPTP-treated common marmosets. We have also studied the effect of increased brain exposure to pulsatile administration by combining a low-dose of L -dopa with the peripheral catechol- O -methyltransferase inhibitor (COMT-I), entacapone. Pulsatile administration of a low (dose range, 5.0,7.5 mg/kg p.o.) or a high (12.5 mg/kg) dose of L -dopa plus carbidopa b.i.d. produced a dose-related reversal of motor deficits. Repeated administration of low and high doses of L -dopa for 26 days to drug-naïve, MPTP-treated animals also caused a dose-related induction of peak-dose dyskinesia. Repeated administration of high-dose L -dopa b.i.d. compared to once daily caused a frequency-related improvement of motor symptoms, resulting in a more rapid and initially more intense appearance of peak-dose dyskinesia. Administration of low-dose L -dopa b.i.d. for 26 days in combination with entacapone enhanced the increase in locomotor activity and reversal of disability produced by L -dopa alone, but with no obvious change in duration of L -dopa's effect. However, combining entacapone with L -dopa resulted in the more rapid appearance of dyskinesia, which was initially more severe than occurred with L -dopa alone. Importantly, increasing pulsatile exposure of brain to L -dopa by preventing its peripheral breakdown also increases dyskinesia induction. © 2003 Movement Disorder Society [source] Quantitative MRI-pathology correlations of brain white matter lesions developing in a non-human primate model of multiple sclerosisNMR IN BIOMEDICINE, Issue 2 2007Erwin L. A. Blezer Abstract Experimental autoimmune encephalomyelitis (EAE) induced with recombinant human myelin/oligodendrocyte glycoprotein in the common marmoset is a useful preclinical model of multiple sclerosis in which white matter lesions can be well visualized with MRI. In this study we characterized lesion progression with quantitative in vivo MRI (4.7,T; T1 relaxation time,±,Gd-DTPA; T2 relaxation time; magnetization transfer ratio, MTR, imaging) and correlated end stage MRI presentation with quantitative ex vivo MRI (formaldehyde fixed brains; T1 and T2 relaxation times; MTR) and histology. The histopathological characterization included axonal density measurements and the numeric quantification of infiltrated macrophages expressing markers for early active [luxol fast blue (LFB) or migration inhibition factor-related protein-14 positive] or late active/inactive [periodic acid Schiff (PAS) positive] demyelinating lesion. MRI experiments were done every two weeks until the monkeys were sacrificed with severe EAE-related motor deficits. Compared with the normal appearing white matter, lesions showed an initial increase in T1 relaxation times, leakage of Gd-DTPA and decrease in MTR values. The progressive enlargement of lesions was associated with stabilized T1 values, while T2 initially increased and stabilized thereafter and MTR remained decreased. Gd-DTPA leakage was highly variable throughout the experiment. MRI characteristics of the cortex and (normal appearing) white matter did not change during the experiment. We observed that in vivo MTR values correlated positively with the number of early active (LFB+) and negatively with late active (PAS+) macrophages. Ex vivo MTR and relaxation times correlated positively with the number of PAS-positive macrophages. None of the investigated MRI parameters correlated with axonal density. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||