Characterization of the nigroestriatal system in a sample of patients with amyotrophic lateral sclerosis / Caracterização do sistema nigroestriatal em uma amostra de pacientes com esclerose lateral amiotrófica

Abstract Background The coexistence of amyotrophic lateral sclerosis (ALS) with clinical forms of Parkinson disease (PD), although uncommon, is found to a greater degree than one would expect by chance. The pathological mechanisms of ALS and PD are still not fully understood, and the coexistence of these two diseases suggests that they could share mechanisms in common. Objective Here we present a sample of patients with clinically definitive or probable ALS who were evaluated with single-photon emission computed tomography SPECT/TRODAT and compared with non-ALS controls. Methods Patients with clinically definite or probable ALS were assessed with the amyotrophic lateral sclerosis functional rating scale (ALSFRS) to define severity and had their demographic data collected. The TRODAT results of patients with ALS were compared with those of patients with a diagnosis of PD with less than 10 years of duration, and with patients with a diagnosis of others movement disorders not associated with neurodegenerative diseases. Results A total of 75% of patients with ALS had TRODAT results below the levels considered normal; that was also true for 25% of the patients in the control group without neurodegenerative disease, and for 100% of the patients in the PD group. A statistically significant difference was found between patients with ALS and the control group without neurodegenerative disease in the TRODAT values < 0.05. Conclusions Our study fits with the neuropathological and functional evidence that demonstrates the existence of nigrostriatal dysfunction in patients with ALS. Further research to better understand the role of these changes in the pathophysiological process of ALS needs to be performed.

Resumo Antecedentes A coexistência da esclerose lateral amiotrófica (ELA) com formas clínicas da doença de Parkinson (DP), embora incomum, é encontrada em um grau maior do que seria esperado ao acaso. Os mecanismos patológicos da ELA e da DP ainda não são totalmente compreendidos e a coexistência dessas duas doenças sugere que elas podem compartilhar mecanismos em comum. Objetivo Apresentamos uma amostra de pacientes com ELA clinicamente definida ou provável que foram avaliados com tomografia computadorizada por emissão de fóton único (SPECT)/TRODAT e comparados com controles sem ELA. Métodos Pacientes com ELA clinicamente definida ou provável foram avaliados com a escala funcional de esclerose lateral amiotrófica (ALSFRS) para definir a gravidade e foram coletados os seus dados demográficos. Os resultados do TRODAT de pacientes com ELA foram comparados com aqueles de pacientes com diagnóstico de DP com menos de 10 anos de duração e com pacientes com diagnóstico de outros distúrbios do movimento não associados a doenças neurodegenerativas. Resultados Um total de 75% dos pacientes com ELA apresentou resultados de TRODAT abaixo dos níveis considerados normais; 25% no grupo controle sem doença neurodegenerativa e 100% no grupo DP. Uma diferença estatisticamente significativa foi encontrada entre os pacientes com ELA e o grupo controle sem doença neurodegenerativa nos valores de TRODAT p< 0,05. Conclusões Nosso estudo está de acordo com as evidências neuropatológicas e funcionais que demonstram a existência de disfunção nigroestriatal em pacientes com ELA. Mais pesquisas para entender melhor o papel dessas mudanças no processo fisiopatológico da ELA precisam ser realizadas.

Study of dopamine-producing cells derived from human umbilical cord mesenchymal stem cells in treatment in rats with Parkinson’s disease / 天津医药

Objective To investigate the efficacy of dopamine producing cells (DPCs) derived from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in treatment in model rats with Parkinson’s disease (PD). Methods The cultured hUC-MSCs were induced into DPCs in vitro. The dopamine (DA) and glial cell line-derived neurotrophic factor (GDNF) expression levels were detected by ELISA to identify the DPCs. The PD rat model was established by injecting 6-OHDA into the right substantia nigra (SN). A total of 60 successfulled PD model rats were randomized into hUC-MSCs-DPCs group (5 × 105 hUC-MSCs-DPCs were transplanted into right striatum, n=20), hUC-MSCs group (5 × 105 hUC-MSCs were transplanted, n=20) and control group (same volume PBS, n=20). All the transplanted cells were labeled with CM-Dil. The apomorphine induced rotation behavior was assessed at 4, 8 and 12 weeks after cell transplantation. The rats were executed after 12 weeks. The immunofluorescence staining was used to detect the tyrosine hydroxylase (TH) expression level, and FLUORO-JADE? C staining was used to test the apoptotic neurons in brain of rats. Results The hUC-MSCs-DPCs were induced successfully in vitro, which showed a high expression level of DA and GDNF. Furthermore, at 4, 8 and 12 weeks after cell transplantation, the rotation behavior was improved, and expression levels of GDNF were significantly higher in hUC-MSCs-DPCs group than those of hUC-MSCs group and control group (P<0.05). In addition, we found that most of the transplanted TH+hUC-MSCs-DPCs at the right striatum and a few cells around both the left and the right substantia nigra at 12 weeks after transplantation. The apoptotic neurons were decreased after cell transplantation in hUC-MSCs-DPCs group than that of control group (P<0.05). Conclusion The hUC-MSCs-DPCs can improve the rotational behavior induced by apomorphine in PD model rats, which may be involved in improving levels of DA and GDNF in damaged striatum and protecting neurons.

Augmented movement strategies for postural control in patients with spinocerebellar ataxia type 3: a case-control study / Estratégias aumentadas de movimento para controle postural em pacientes com ataxia espinocerebellar tipo 3: caso-controle

INTRODUCTION: This study investigated the movement strategies for postural control in patients with spinocerebellar ataxia type 3 (SCA3). METHODS: This case-control study enrolled 5 patients with SCA3 (aged 41 to 51 years) and 5 healthy participants group-matched by age, body mass and body height.Participants performed 3 trials lasting 30 s each of postural tasks characterized by: feet apart or together; eyes open or closed. Center of pressure (CoP) data was quantified using three-dimensional (3D: number of high-density and high-speed regions, average and maximal distances among regions), two-dimensional (2D: elliptical area, average velocity) and one-dimensional (1D: standard deviation, velocity) parameters. RESULTS: Analysis of variance revealed significant interaction effect between group*task for 1D (F12,238=3.496, p<0.001), 2D (F6,184=11.472, p<0.001), and 3D parameters (F12,238=2.543, p=0.004). Significant univariate effects for postural task were observed for all parameters, with higher body sway values under visual and biomechanical constraints, either separated or combined. CONCLUSIONS: Patients with SCA3 presented augmented movement strategiescompared with healthy subjects, characterized by increasing body sway under more demanding biomechanical and/ or visual constraints. Three-dimensional kinematic mapping revealed either random movement strategies or a unique movement strategy characterized by a stochastic CoP distribution, with high CoP speed to correct for large body sway deviations.

INTRODUÇÃO: Este estudo investigou as estratégias de movimento para controle postural em pacientes com ataxia espinocerebelar tipo 3 (SCA3). MÉTODOS: Este estudo de caso-controle incluiu cinco pacientes com SCA3 (idade 41 a 51 anos) e cinco participantes saudáveis, agrupados por idade, massa corporal e altura corporal. Os participantes realizaram três ensaios 30 s cada uma das tarefas posturais caracterizadas por: pés separados ou juntos; olhos abertos ou fechados. Os dados do centro de pressão (CoP) foram quantificados usando tridimensional (3D: número de alta densidade e alta velocidade regiões, distâncias médias e máximas entre regiões), bidimensional (2D: área elíptica, velocidade média) e unidimensional (1D: Desvio padrão, velocidade). RESULTADOS: Análise de variância Revelou um efeito de interação significativo entre a tarefa * grupo 1D (F12.238 = 3.496, p <0.001), 2D (F6.184 = 11.472, p <0.001) e os parâmetros 3D (F12,238 = 2,543, p = 0,004). Efeitos univariados significativos foram observados para todos os parâmetros, com maiores valores de balanço corporal sob restrições visuais e biomecânicas, separadas ou combinados. CONCLUSÕES: Os pacientes com SCA3 apresentaram estratégias de movimento comparadas com indivíduos saudáveis, aumentando o balanço do corpo sob condições biomecânicas e / ou restrições visuais. O mapeamento cinemático tridimensional revelou estratégias de movimento aleatório ou uma estratégia de movimento caracterizada por uma distribuição estocástica de CoP, com alta velocidade de correção para os grandes desvios.

A Rat Model of Striatonigral Degeneration Generated by Simultaneous Injection of 6-Hydroxydopamine into the Medial Forebrain Bundle and Quinolinic Acid into the Striatum

A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.

Diffusion changes in substantia nigra following striatum infarction with diffusion tensor imaging / 中华神经科杂志

Objective To investigate the diffusion changes in ipsilateral substantia nigra after a chronic striatum infarction with diffusion tensor imaging ( DTI ) and its connotation for clinical lecture.Methods Participators underwent a DTI scan and were divided into three groups. The striatum infarction (SI) group consisted of twenty patients with chronic basal ganglia infarction with striatum involved, while the non striatum infarction (NSI) group consisted of another twenty patients with chronic basal ganglia infarctions without striatum involved. The control group consisted of twenty healthy volunteers. Before the DTI scan all patients underwent a clinical evaluation with Modified Rankin Scale (mRS) and Barthol Index,and the four patients of SI group with symptoms like Parkinson disease underwent an additional evaluation with the third subscale of Unified Parkinson' s Disease Rating Scale ( UPDRS Ⅲ ). Results Compared with NSI and control groups, the infarct side substantia nigra MD of SI group increased by 30. 86 percent (t =40.07,P=0.000) and 31.42 percent (t =42. 64,P =0.000). The FA values from the three groups were not different. There were four patients with some symptoms like Parkinson disease in SI group. Compared with those patients without symptom like Parkinson disease in SI group, the infarct side substantia nigra MD of these four patients increased by 22 percent(t = 18.03, P =0. 01 ). Moreover, the infarct side substantia nigra MD of these four patients was correlated with their UPDRS Ⅲ positively ( r = 0. 97, P = 0. 03 ).Conclusions The secondary degeneration in the ipsilateral side substantia nigra after striatum infarction could be detested quantitatively with diffusion tensor imaging. The secondary degeneration in substantia nigra may be responsible for the symptoms like Parkinson disease in striatum infarction patients.

MRI comparative study of the progressive supranuclear palsy, striatonigral degeneration and Parkinson disease / 中华放射学杂志

Objective To provide a reliable differential diagnosis among the progressive supranuclear palsy ( PSP), striatonigral degeneration ( SND ) and Parkinson disease ( PD ) . Methods Conventional MRI data in clinically proved PSP(8 cases), SND(9 cases), PI)( 12 cases)and 12 normal controls were retrospectively analyzed. Midbrain area, pons area, ports diameter and middle eerebellar peduncles width were measured. The ratio of pons area over midbrain area (pons area/midbrain area) was calculated in all patients and normal controls. Then one way ANOVA and a Kruskal-Wallis H test were used for statistical analysis. Results Midbrain area of the PSP group [ (85. 8±12. 0) mm2 ] was the smallest, and there was statistically significant difference ( P < 0. 05 ) comparing with the SND group [ ( 133.2± 8. 4) nun2 ], PD group[ ( 133. 5±10. 8) mm2 ] and the control group [ ( 135.9±7.5 ) mm2 ]. There was no overlapping in the distribution of midbrain area between the PSP group(66.0-98. 2 mm2 ) and SND, PD and normal groups( 116. 2-142. 1, 110. 8-146. 2 and 121.7-145.8 mm2 ). The pons area-midbrain area ratio (P/M) of the PSP group (5.9±0. 8) was the largest in four groups, and there was statistically significant difference ( P < 0. 05 ) comparing with the SN D group ( 2. 9±0. 5 ), PD group ( 3.8±0. 3 ) and the control group (3. 8±0. 3 ). There was no overlapping in the distribution of P/M between the PSP group(5.0-7.2) and SND,PD and normal groups(2. 2-3.5, 3. 3-4. 6 and 3. 2-4. 2). SND group had the smallest P/M, pens area, pons diameter and middle cerebellar peduncles width [ 2.9±0. 5, ( 384. 8±62. 6) mm2 , ( 18. 6±2. 0) nun and( 12. 9±2. 4) mm ] in all groups, and significant difference ( P < 0. 05 ) was found comparing with the PSP group[5.9±0. 8, (500.1±21.8)mm2, (22. 7±1.7)mm and( 16. 3±1. 1) nun],PD group[3.8±0.3, (500.2±25.8)mm2, (23.7±1.0)mm and(16.8±1. 1)mm]and the control group [3. 8±0. 3, ( 508. 8±20. 6 ) mm2, ( 23.2±1.2) nun and ( 16. 4±0. 9 ) mm]. But the PD group and control group had no statistically significant difference in the midbrain area, pans area, pons diameter, P/M and middle cerebellar peduncles width ( P > 0. 05 ). Conclusion MRI measurements helps in the differential diagnosis among PSP, SND and PD.