IL-12p40 Deficiency Leads to Uncontrolled Trypanosoma cruzi Dissemination in the Spinal Cord Resulting in Neuronal Death and Motor Dysfunction

Chagas' disease is a protozoosis caused by Trypanosoma cruzi that frequently shows severe chronic clinical complications of the heart or digestive system. Neurological disorders due to T. cruzi infection are also described in children and immunosuppressed hosts. We have previously reported that IL-12p40 knockout (KO) mice infected with the T. cruzi strain Sylvio X10/4 develop spinal cord neurodegenerative disease. Here, we further characterized neuropathology, parasite burden and inflammatory component associated to the fatal neurological disorder occurring in this mouse model. Forelimb paralysis in infected IL-12p40KO mice was associated with 60% (p<0.05) decrease in spinal cord neuronal density, glutamate accumulation (153%, p<0.05) and strong demyelization in lesion areas, mostly in those showing heavy protein nitrosylation, all denoting a neurotoxic degenerative profile. Quantification of T. cruzi 18S rRNA showed that parasite burden was controlled in the spinal cord of WT mice, decreasing from the fifth week after infection, but progressive parasite dissemination was observed in IL-12p40KO cords concurrent with significant accumulation of the astrocytic marker GFAP (317.0%, p<0.01) and 8-fold increase in macrophages/microglia (p<0.01), 36.3% (p<0.01) of which were infected. Similarly, mRNA levels for CD3, TNF-alpha, IFN-gamma, iNOS, IL-10 and arginase I declined in WT spinal cords about the fourth or fifth week after infection, but kept increasing in IL-12p40KO mice. Interestingly, compared to WT tissue, lower mRNA levels for IFN-gamma were observed in the IL-12p40KO spinal cords up to the fourth week of infection. Together the data suggest that impairments of parasite clearance mechanisms in IL-12p40KO mice elicit prolonged spinal cord inflammation that in turn leads to irreversible neurodegenerative lesions.

More severe functional impairment in dementia with Lewy bodies than Alzheimer disease is related to extrapyramidal motor dysfunction.

OBJECTIVE The objective of this study was to compare functional impairments in dementia with Lewy bodies (DLB) and Alzheimer disease (AD) and their relationship with motor and neuropsychiatric symptoms. METHODS The authors conducted a cross-sectional study of 84 patients with DLB or AD in a secondary care setting. Patients were diagnosed according to published criteria for DLB and AD. The Bristol Activities of Daily Living Scale (BADLS) was used to assess functional impairments. Participants were also assessed using the Unified Parkinson's Disease Rating Scale (motor section), the Neuropsychiatric Inventory, and the Mini-Mental Status Examination. RESULTS Patients with DLB were more functionally impaired and had more motor and neuropsychiatric difficulties than patients with AD with similar cognitive scores. In both AD and DLB, there were correlations between total BADLS scores and motor and neuropsychiatric deficits. There was more impairment in the mobility and self-care components of the BADLS in DLB than in AD, and in DLB, these were highly correlated with UPDRS score. In AD, orientation and instrumental BADLS components were most affected. CONCLUSION The nature of functional disability differs between AD and DLB with additional impairments in mobility and self-care in DLB being mainly attributable to extrapyramidal motor symptoms. Consideration of these is important in assessment and management. Activities of daily living scales for use in this population should attribute the extent to which functional disabilities are related to cognitive, psychiatric, or motor dysfunction.

Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision

Background: Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. Objective: To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. Methods: A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. Results: All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. Conclusions: In typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment.

Development of motor system dysfunction following whiplash injury

Dysfunction in the motor system is a feature of persistent whiplash associated disorders. Little is known about motor dysfunction in the early stages following injury and of its progress in those persons who recover and those who develop persistent symptoms. This study measured prospectively, motor system function (cervical range of movement (ROM), joint position error (JPE) and activity of the superficial neck flexors (EMG) during a test of cranio-cervical flexion) as well as a measure of fear of re-injury (TAMPA) in 66 whiplash subjects within 1 month of injury and then 2 and 3 months post injury. Subjects were classified at 3 months post injury using scores on the neck disability index: recovered (30). Motor system function was also measured in 20 control subjects. All whiplash groups demonstrated decreased ROM and increased EMG (compared to controls) at 1 month post injury. This deficit persisted in the group with moderate/severe symptoms but returned to within normal limits in those who had recovered or reported persistent mild pain at 3 months. Increased EMG persisted for 3 months in all whiplash groups. Only the moderate/severe group showed greater JPE, within 1 month of injury, which remained unchanged at 3 months. TAMPA scores of the moderate/severe group were higher than those of the other two groups. The differences in TAMPA did not impact on ROM, EMG or JPE. This study identifies, for the first time, deficits in the motor system, as early as 1 month post whiplash injury, that persisted not only in those reporting moderate/severe symptoms at 3 months but also in subjects who recovered and those with persistent mild symptoms. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

Análise do padrão motor em pessoas com diagnóstico de esquizofrenia: uma abordagem em tempo real

A esquizofrenia é uma perturbação mental grave caracterizada pela coexistência de sintomas positivos, negativos e de desorganização do pensamento e do comportamento. As alterações motoras são consistentemente observadas mas, ainda pouco estudadas na esquizofrenia, sendo relevantes para o seu diagnóstico. Neste quadro, o presente estudo tem como objetivo verificar se os indivíduos com esquizofrenia apresentam alterações na coordenação motora, comparativamente com o grupo sem esquizofrenia, bem como analisar se as disfunções dos sinais neurológicos subtis (SNS) motores se encontram correlacionadas com o funcionamento executivo e com os domínios psicopatológicos da perturbação. No total participaram 29 indivíduos (13 com diagnóstico de esquizofrenia e 16 sem diagnóstico) equivalentes em termos de idade, género, escolaridade e índice de massa corporal. Para avaliar o desempenho motor recorreu-se ao sistema Biostage de parametrização do movimento em tempo real, com a tarefa de lançameto ao alvo; a presença de SNS foi examinada através da Brief Motor Scale; o funcionamento executivo pela aplicação do subteste do Vocabulário e da fluência verbal e a sintomatologia clínica através da Positive and Negative Sindrome Scale. Pela análise cinemática do movimento constatou-se que os indivíduos com esquizofrenia recrutam um padrão motor menos desenvolvido e imaturo de movimento, com menor individualização das componentes (principalmente do tronco e pélvis), necessitando de mais tempo para executar a tarefa, comparativamente com os sujeitos sem a perturbação que evidenciaram um movimento mais avançado de movimento. Os indivíduos com esquizofrenia mostraram índices elevados de disfunção dos SNS (média =6,01) estabelecendo este domínio uma relação boa e negativa com o desempenho verbal (rho Spearman=-0,62) e uma relação forte e positiva com todos os domínios psicopatológicos (rho Spearman=0,74). O estudo da existência de alterações motoras como parte intrínseca da esquizofrenia revela-se pertinente uma vez que possibilita uma compreensão mais aprofundada da sua fisiopatologia e permite que se desenvolvam práticas mais efetivas na área da saúde e reabilitação.

Primary motor cortex involvement in Alzheimer disease.

In Alzheimer disease (AD) the involvement of entorhinal cortex, hippocampus, and associative cortical areas is well established. Regarding the involvement of the primary motor cortex the reported data are contradictory. In order to determine whether the primary motor cortex is involved in AD, the brains of 29 autopsy cases were studied, including, 17 cases with severe cortical AD-type changes with definite diagnoses of AD, 7 age-matched cases with discrete to moderate cortical AD-type changes, and 5 control cases without any AD-type cortical changes. Morphometric analysis of the cortical surface occupied by senile plaques (SPs) on beta-amyloid-immunostained sections and quantitative analysis of neurofibrillary tangles (NFTs) on Gallyas-stained sections was performed in 5 different cortical areas including the primary motor cortex. The percentage of cortical surface occupied by SPs was similar in all cortical areas, without significant difference and corresponded to 16.7% in entorhinal cortex, 21.3% in frontal associative, 16% in parietal associative, and 15.8% in primary motor cortex. The number of NFTs in the entorhinal cortex was significantly higher (41 per 0.4 mm2), compared with those in other cortical areas (20.5 in frontal, 17.9 in parietal and 11.5 in the primary motor cortex). Our findings indicate that the primary motor cortex is significantly involved in AD and suggest the appearance of motor dysfunction in late and terminal stages of the disease.

Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

Avaliação do desempenho funcional de crianças com paralisia cerebral de acordo com níveis de comprometimento motor

Contextualization: Several studies have examined the mobility of this group of children, however little is known about the impact of motor function in activities of daily living, considering the seriousness of their neuromotor damage. Objective: Identify the functional differences of children with Cerebral Palsy with different levels of motor dysfunction and correlate these differences with the areas of mobility, self-care and social function in functional ability and caregiver´s assistance of these children. Methods: An l analytical cross-section search was developed, which were part 70 children / families aged from 4 to 7.5 years, in the Rehabilitation Center for Children. As tools were used the Pediatric Evaluation Disability Inventory (PEDI) and the Gross Motor Function Classification System (GMFCS). Data analysis was performed by ANOVA and Pearson's correlation tests. Results: The results show the functional variability of children CP in different severity levels of motor disfunction This variation was observed in the areas of mobility, self-care and social function. The results also showed a strong correlation between the domains mobility and self-care, mobility and social function. Conclusions: The variability shown by the children with CP, suggests the use of PEDI and GMFCS as this association appears to increase the understanding of how the gross motor functions are related to activities of daily living, describing the best commitments and their degree of impact on functional activities. This correlation demonstrates how mobility is crucial to evaluate the performance and guide the therapeutic practice, to develop the children´s potencial, and guide the caregiver in stimulation

Alternative pathways for catecholamine action in oral motor control

Orofacial movement is a complex function performed by facial and jaw muscles. Jaw movement is enacted through the triggering of motoneurons located primarily in the trigeminal motor nucleus (Mo5). The Mo5 is located in the pontine reticular formation, which is encircled by premotor neurons. Previous studies using retrograde tracers have demonstrated that premotor neurons innervating the Mo5 are distributed in brainstem areas, and electrophysiological studies have suggested the existence of a subcortical relay in the corticofugal-Mo5 pathway. Various neurotransmitters have been implicated in oral movement. Dopamine is of special interest since its imbalance may produce changes in basal ganglia activity, which generates abnormal movements, including jaw motor dysfunction, as in oral dyskinesia and possibly in bruxism. However, the anatomical pathways connecting the dopaminergic systems with Mo5 motoneurons have not been studied systematically. After injecting retrograde tracer fluorogold into the Mo5, we observed retrograde-labeled neurons in brainstem areas and in a few forebrain nuclei, such as the central nucleus of the amygdala, and the parasubthalamic nucleus. By using dual-labeled immunohistochemistry, we found tyrosine hydroxylase (a catecholamine-processing enzyme) immunoreactive fibers in close apposition to retrograde-labeled neurons in brainstem nuclei, in the central nucleus of the amygdala and the parasubthalamic nucleus, suggesting the occurrence of synaptic contacts. Therefore, we suggested that catecholamines may regulate oralfacial movements through the premotor brainstem nuclei, which are related to masticatory control, and forebrain areas related to autonomic and stress responses. (C) 2005 Elsevier B.V.. All rights reserved.

Síntomas depresivos y trastorno motor en pacientes con enfermedad de Parkinson

Introduction. Complex relations between brain and psychopathology have attracted the interest of researchers, aiming to clarify the neurobiological mechanisms of depression in Parkinson's disease, obviously in addiction to mental features. Aims. The association of motor impairment and decline of personal autonomy with severity of depressive symptoms was the hypothesis of the present study. Aiming to check this hypothesis, the objective of this study consisted in investigating relationships between the severity of depressive symptoms and motor characteristics of Parkinson's disease. Patients and methods. Thirty patients (53 to 80 year-old) with medical diagnosis of idiopathic Parkinson's disease in initial clinic stages were studied. The Unified Parkinson's Disease Rating Scale, Hoehn-Yahr Scale, and Schwab & England Scale were used to assess the clinic signs and symptoms. The depressive symptoms were identified by complete anamnesis, examination of mental condition, and the Hamilton Rating Scale for Depression and the Anxiety and Depression Scale. Statistical analysis was performed by Pearson's correlation and multiple regression analysis. Results. A significant correlation of severity of depression symptoms with disease stage (p < 0.02), with motor signs (p < 0.008), and with functional performance (p < 0.007) was found. Conclusion. There was significant association between motor impairment and severity of depressive symptoms, and between depression and early disease onset or prolonged duration of Parkinson's disease. © 2007, Revista de Neurología.

Calpain inhibitor AK295 attenuates motor and cognitive deficits following experimental brain injury in the rat.

Marked increases in intracellular calcium may play a role in mediating cellular dysfunction and death following central nervous system trauma, in part through the activation of the calcium-dependent neutral protease calpain. In this study, we evaluated the effect of the calpain inhibitor AK295 [Z-Leu-aminobutyric acid-CONH(CH2)3-morpholine] on cognitive and motor deficits following lateral fluid percussion brain injury in rats. Before injury, male Sprague-Dawley rats (350-425 g) were trained to perform a beam-walking task and to learn a cognitive test using a Morris water maze paradigm. Animals were subjected to fluid percussion injury (2.2-2.4 atm; 1 atm = 101.3 kPa) and, beginning at 15 min postinjury, received a continuous intraarterial infusion of AK295 (120-140 mg/kg, n = 15) or vehicle (n= 16) for 48 hr. Sham (uninjured) animals received either drug (n = 5) or vehicle (n = 10). Animals were evaluated for neurobehavioral motor function at 48 hr and 7 days postinjury and were tested in the Morris water maze to evaluate memory retention at 7 days postinjury. At 48 hr, both vehicle- and AK295-treated injured animals showed significant neuromotor deficits (P< 0.005). At 7 days, injured animals that received vehicle continued to exhibit significant motor dysfunction (P< 0.01). However, brain-injured, AK295-treated animals showed markedly improved motor scores (P<0.02), which were not significantly different from sham (uninjured) animals. Vehicle-treated, injured animals demonstrated a profound cognitive deficit (P< 0.001), which was significantly attenuated by AK295 treatment (P< 0.05). To our knowledge, this study is the first to use a calpain inhibitor following brain trauma and suggests that calpain plays a role in the posttraumatic events underlying memory and neuromotor dysfunction.

Corticosteroid therapy in TSP/HAM patients: The results from a 10 years open cohort

Background: The use of corticosteroids for treating tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) has yielded controversial results. We report the use of corticosteroids for the treatment of TSP/HAM in an open cohort. Methods: The clinical efficacy of long-term, high dose of corticosteroid therapy was studied in thirty-nine TSP/HAM patients. Disability and motor dysfunction was evaluated based on the Disability Status Scale (DSS), Osame`s Motor Disability Scales (OMDS), and Incapacity Status Scale (ISS), before and after treatment. Treatment included use of methyl-predmisolone, 1 g/day for three days, every 3-4 months. The primary end-point was a change in the scores of the neurological scales from baseline until the fifth visit after therapy. Results: After a mean follow-up of 2.2 years and an average of four pulses per patient, we noted a significant neurological improvement, reaching 24.5% according to the ISS score. No statistically significant differences in scores according to the OMDS and DSS scales were noted. Conclusion: We observed neurological improvement with the use of corticosteroids, with physical therapy and anti spastic-drugs as adjunctive treatment. However, randomized clinical trials should be done to assess the use of corticosteroids and other potentially useful immune-based therapies for TSP/HAM treatment. (C) 2008 Elsevier B.V. All rights reserved.