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Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that affects 11% of children in the US alo­ne. Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of ADHD. Given the fact that ADHD symptoms persist in up to 50% of patients, many children receive MPH from childhood to early adulthood. Unfortunately, most of the scientific literature focuses on the short-term consequences of MPH, even though individuals are taking MPH for many years. Previous research has shown that long-term exposure to MPH causes dopamine-releasing neurons within the nigrostriatal pathway to die when exposed to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPH acts by blocking dopamine transporters and norepinephrine transporters, preventing the reuptake and removal of these neurotransmitters following release and increasing the time outside of the protective environment of the neuron’s vesicles. We hypothesize that spontaneous oxidation of excess dopamine to a quinone metabolite is rendering these neurons within this particular pathway to be more sensitive to MPTP. The dopamine quinone may be bound by the antioxidant glutathione (GSH) in an effort to protect the cell against oxidative stress. However, as the finite amount of GSH is depleted, the quinone may lead to the production of highly reactive molecules, leading to mitochondrial damage and cell death which may be accelerated by MPTP. In order to examine this hypothesis, we chose to study adolescent male Swiss-Webster mice, which have been shown to be resistant to MPTP’s toxic effects. They were divided into 3 cohorts and administered either saline (control), 1 mg/kg MPH (therapeutic dose) or 10 mg/kg (abusive dose) via intraperitoneal (IP) injections for 12 weeks. Mice were injected twice daily, Monday through Friday, mimicking a school-week dosing schedule. After 12 weeks, all animals received a drug washout period of 7 days. Then, half of each cohort was treated with MPTP (4 x 20 mg/kg, every 2 hours), while the other half was administered 4 injections of sterile saline. Either 3 or 7 days after MPTP or saline treatment, the mice were sacrificed, brains were removed, and the substantia nigra (SN) and striatum (STR) were collected. These areas of the brain make up the nigrostriatal pathway and are affected by Parkinson’s disease. Oxidative stress related to increased dopamine levels was determined using the glutathione assay to measure GSH content, near-infrared fluorescence dot blots to measure free and protein-bound ortho-quinones, and an ATP luciferase assay to measure mitochondrial function. Interestingly, there was a significant decrease in GSH as the dose of MPH was increased with both saline and MPTP samples. Furthermore, a significant increase in quinones was observed as the dose of MPH increased. We also expect to see a decrease in ATP inversely proportional to the dose of MPH indicating increased oxidative stress. In conclusion, it appears that long-term exposure to MPH sensitizes dopaminergic neurons within the nigrostriatal pathway to oxidative stress, rendering them vulnerable to further insults, such as MPTP exposure. As such, these studies provide insight into the risks of long-term psychostimulant exposure.

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<p dir="ltr">Telehealth is an increasingly popular treatment option for people with Parkinson disease (PD). The SpeechVive device is a wearable device that uses the Lombard effect to help patients speak more loudly, slowly, and clearly. This study sought to examine the effectiveness of the device to improve communication in people with PD, delivered in-person and over a telehealth modality using an implementation science design. Sixty-six (66) people with PD were enrolled for twelve (12) weeks with thirty-four (34) choosing the in-person group and thirty-two (32) in the telehealth group. Participants were assessed pre-, mid-, and post-treatment. Participants produced continuous speech samples with and without the device at each timepoint. Sound pressure level (SPL), utterance length, pause frequency, and total pause duration were measured. Psychosocial questionnaires were administered to evaluate the effects of treatment on depression, self-efficacy, and participation. The in-person group increased SPL when wearing the device while the telehealth group did not. Both groups paused less often while wearing the device. Utterance length increased post-treatment for the telehealth group, but not for the in-person group. An increase in communication participation ratings in the telehealth group, but not the in-person group, was the only significant change in the psychosocial metrics. The in-person group showed similar treatment effects as previous studies. The device had less effect on intensity in the telehealth group but improved comminicative participation ratings more, as compared to in-person. One limitation was data loss due to recording issues that impacted the telehealth group more than the in-person group.</p>

Rigidity is one of the cardinal symptoms in Parkinson's disease, along with Bradykinesia, tremor and postural instability. Rigidity in PD has been understudied, but its pathophysiological basis remains unclear. Various types of neurophysiological and biomechanical approach have been developed in order to investigate the neural control of muscle tone. A common approach is to observe the sensitivity of muscle resistance in response to stretch velocity or displacement [Kamper, Rea, He]. A recent study on elbow flexors in patients with spasticity and rigidity showed a velocity dependent increase in reactive torque in both groups [Lee H, et al). Even though this Study shows a correlation between elbow flexors and velocity, it doesn't discuss the role of elbow extensors. We studied the rigidity response in the elbow of both arms to different speed movements in 12 patients suffering from Parkinson's disease ON or OFF medication. The purpose of this study was to look at both elbow flexion and extension and show that quantitative measures of rigidity and movement disorders in subjects with Parkinson's disease correlate with the currently used clinical evaluations and also find the correlation between velocity and both elbow extension and flexion at the same time. Elbow was flexed and extended by means of a robotic arm,under four different speeds. The resistance to movement was recorded with a torque sensor and EMG of two elbow muscles; Biceps and Triceps; was recorded while the subjects were attempting to relax. The patients were also examined by physicians and their elbow rigidity and muscle tone and Parkinson's disease stage was evaluated and a Universal score in the categories of UPDRS, MMSE, and CAPIT was assigned for each arm of each individual. In the end we will argue that there is a very strong correlation between speed and elbow Extension and Flexion, muscle activity and the rigidity presented in each arm. We will also present the correlation between the robotic torque measurement and the clinical scores given to each subject.

Este trabalho tem o objetivo avaliar o efeito da adrenalectomia bilateral no processo neurodegenerativo e cicatricial na via nigro estriatal dopaminérgica lesada pela 6- hidroxidopamina (6-OHDA) em ratos, e deste modo contribuir para a interpretação dos efeitos dos hormônios adreno esteróides nos processos neurodegenerativos e neurotróficos nas lesões do sistema nervoso central. Ratos Wistar adultos jovens foram submetidos à cirurgia de retirada bilateral das glândulas adrenais ou cirurgia simulada para a mesma. Após 2 dias, os animais foram submetidos à cirurgia estereotáxica para lesão do sistema nigro estriatal dopaminérgico através da injeção unilateral de 6-OHDA na substância negra. Os animais receberam diariamente doses de reposição hormonal de corticosterona (10mg/kg) ou solução veículo. Após um período de 72 horas, 1 semana e 3 semanas, os animais foram sacrificados por decapitação, e as regiões do mesencéfalo ventral e corpo estriado foram dissecados bilateralmente. O tecido foi processado para o método de Western blot onde foram analisados os seguintes marcadores: tirosina hidroxilase (TH enzima que participa da via de conversão da dopamina), proteína ácida fibrilar glial (GFAP proteína do filamento intermediário do citoesqueleto do astrócito), bem como as moléculas da matriz extracelular fosfacan, neurocan, sulfato de condroitina e NG2, a proteína Laminina e finalmente, o fator de crescimento fibroblástico-2 (FGF-2) na região do mesencéfalo ventral, onde observa-se ações tróficas nos neurônios dopaminérgicos nigras que podem exercer efeitos no processo inflamatório pelas suas ações gliogênica e angiogênica. Deste modo, a neurodegeneração dopaminérgica foi avaliada pelos níveis da TH, a ativação astrocitária pelos níveis da GFAP, o processo de cicatrização pela regulação das moléculas da matriz extracelular e as respostas tróficas pelo FGF-2. Pelos resultados obtidos é possível que hormônios glicocorticóides adrenais modulem os elementos envolvidos na neurodegeneração e reparo e cicatrização do sistema dopaminérgico. / This study has the objective to evaluate the effect of the bilateral adrenalectomy in the neurodegenerative process and cicatrization on the nigroestriatal pathway injury through 6-hydroxydopamine (6-OHDA) in rat, and in this way contribute for the interpretation of the adreno esteroides hormones effects in the neurodegenerative and neurotrophics process in the central nervous system.injury Adult rats wistar were submitted in a surgery to take the bilateral adrenal gland or a simulate surgery of the same. After 2 days the animals was involved into a stereotaxic surgery to nigroestriatal dopaminergic lesion with a unilateral injection of the 6-OHDA in the nigra. The animals received daily corticosterone hormonal (10mg/kg) or vehicle solution. After a period of 72 hours, 1 week and 3 weeks, the animals were decapitated, and the regions of the ventral midbrain and striatum it was bilaterally dissected. The tissue was processed by Western blot method and analyzed for the following markers: tyrosine hydroxylase (TH - enzyme that join of the dopamine conversion pathway), glial fibrilar acid protein (GFAP protein of the intermediary filament of the astrocyte citoesqueleto, the moleculars extracellular matrix phosphacan, neurocan, chondroitin sulfate and NG2, the Laminin protein and finally, the neurotrophic factor (FGF-2) in the region of ventral midbrain, where watched trophic actions in the dopaminergic neurons that could have effects in the inflammatory processes by your gliogenic and angiogenic actions. In this way, the dopaminergic neurodegeneration was evaluated by the TH levels, the astrocytary activation by the GFAP levels, the cicatrization processes by the molecules regulation of the extracellular matrix and the trophics FGF-2 answers. By the results it is possible that adrenal glucocorticoid hormones modulate the elements involved in neurodegeneration, repair and cicatrization of the dopaminergic system.

A doença de Parkinson é uma doença crônica, degenerativa que afeta principalmente funções motora e mentais do indivíduo. Dentre os principais sintomas motores da doença então tremor, rigidez, bradicinesia, instabilidade postural que associados levam a importantes alterações na marcha. A prática mental vem sendo usada como uma estratégia na reabilitação de pacientes com diversas doenças, mas ainda na Doença de Parkinson não temos muitas evidências de sua eficácia. Este estudo tem como objetivo então avaliar o efeito de um protocolo de prática mental associado à prática física no desempenho da marcha de pacientes com Doença de Parkinson. Foram incluídos 20 pacientes nos estágios I, II e III da Escala Modificada de Hoehn e Yahr, que deambulavam sem dispositivos de auxílio, (níveis 3 a 5 da Categoria de Deambulação Funcional FAC), obtinham pontuação maios que 15 pontos na UPDRS e pontuação > 24 pontos no MMSE. O grupo experimental (GE) recebrá uma treinamento de PM da marcha associado a PF, guiado por estratégias cognitiva e o grupo controle (GC) recebeu recebeu um treinamento de PM não relacionada a marcha associada a mesma PF do grupo GE. O desempenho de marcha será avaliado pelo Teste de Caminhada de 6 minutos, UPDRS, Teste de marcha de 30 segundos em condição simples e de dupla tarefa, domínio de marcha da BesTest e a cognição pelo Montreal Cognitive Assessment (MoCA). Foram realizadas 8 sessões de treinamento. Os resultados mostraram que o GE obteve uma melhora significativa maior ao GC na pontuação do BesTest e também no MoCA. Em conclusão, o presente trabalho evidenciou que a adição da PM a um programa de treinamento de prática física tem benefícios no desempenho da marcha e de domínios cognitivos / Parkinson\'s disease is a chronic, degenerative disease that primarily affects the motor and mental functions of the individual. Among the main motor symptoms of the disease then tremor, stiffness, bradykinesia, postural instability associated with it lead to important gait changes. Mental practice has been used as a strategy in the rehabilitation of patients with various diseases, but we still do not have much evidence of its efficacy in Parkinson\'s disease. The objective of this study was to evaluate the effect of a protocol of mental practice associated with physical practice in the gait performance of patients with Parkinson\'s disease. Twenty patients in stages I, II and III of the Modified Scale of Hoehn and Yahr, who wandered without assistive devices (levels 3 to 5 of the Functional Ambulation Category - FAC), were given a score of 15 points in the UPDRS and scored> 24 points in the MMSE. The experimental group (GE) received MP training associated with PF, guided by cognitive strategies and the control group (CG) received received non-gait PM training associated with the same PF of the GI group. The gait performance will be evaluated by the 6-minute Walk Test, UPDRS, 30-second gait test in single and dual-task conditions, BesTest and the cognition by the Montreal Cognitive Assessment (MoCA). Eight training sessions were held. The results showed that the GE obtained a significant improvement to the GC in the BesTest score and also in the MoCA. In conclusion, the present study showed that the addition of PM to a physical training program has benefits in gait performance and cognitive domains

A capacidade do ferro, presente no corpo humano, em aceitar e doar elétrons o torna essencial para homeostase celular e várias reações biológicas. Contudo, o excesso deste metal no cérebro pode gerar efeitos deletérios através da produção de espécies reativas de oxigênio que causam o estresse oxidativo. Este estresse aparece como possível causa de doenças neurodegenerativas, caracterizadas por um aumento significativo da concentração de ferro em certas regiões do cérebro. Detectar e quantificar a deposição de ferro in vivo no cérebro torna-se de extrema relevância para entender diversas doenças neurodegenerativas. Neste estudo avaliamos a sensibilidade e a especificidade das principais técnicas de Ressonância Magnética in vivo para estimar o conteúdo de ferro depositado no cérebro. Foram estudados um grupo de 16 sujeitos saudáveis e outro de 14 pacientes com doença de Parkinson. Mapas de relaxometria (R2 e R2*) e susceptibilidade (QSM) foram estimados a partir de imagens adquiridas numa maquina de RM de 3.0T. Embora todos os mapas tenham apresentado correlação linear (r2 = 0; 7) com o acumulo de ferro reportado in vitro nas regiões do núcleo da base, apenas os mapas R2 e QSM apresentaram estatisticamente aumento significativo (p<0,05) para certas regiões do cérebro parkinsoniano (substância negra, núcleo rubro e globo pálido). O mapa QSM apresentou maior sensibilidade e especificidade para diferenciar pacientes com a doença quando comparados a sujeitos saudáveis por meio da análise da curva ROC. Concluímos que os mapas de relaxometria e susceptibilidade magnética podem estimar de forma indireta o conteúdo de ferro no cérebro, apesar de apresentarem dependências diferentes com a concentração deste metal. Observamos também que os valores de sususceptibilidade magnética obtidos com imagens de baixa resolução (1,0x1,0x2,0mm) não apresentaram mudanças significativas em relação aos obtidos com imagens de alta resolução (0,5x0,5x2,0mm). Logo, sugerimos a aquisição de imagens com baixa resolução para o processamento do mapa QSM. A analise de múltiplos valores de tempo de relaxação T2 determinou apenas um valor para cada região do núcleo da base para ambos os grupos, este resultado foi aparentemente afetado pela relação sinal ruído. / The capacity of the iron present in the human body to accept and donate electrons makes it essential for cellular homeostasis and various biological reactions. However, an excess of the metal in the brain can produce deleterious effects through the production of reactive oxygen species that cause oxidative stress. This stress can be the possible cause of neurodegenerative diseases which present a significant increase in iron concentration in certain brain regions. To detect and quantify iron deposition in the brain in vivo has high potential for understanding neurodegenerative diseases. In this study we evaluated the sensitivity and specificity of the main Magnetic Resonance technique in vivo to estimate the content of iron deposited in the brain. Were studied a group of 16 controls and 14 patient with Parkinson disease. Relaxometry map (R2 and R2*) and magnetic susceptibility map QSM were estimated by images obtained of scanner of Magnetic Resonance of 3T. Although all maps have presented linear correlation (r2=0.7) with the accumulation of iron reported in vitro regions of basal ganglia, only the R2 and QSM maps showed significant increase (p < 0.05) for certain regions of the parkinsonian brain (substantia nigra, red nucleus, and globus pallidus). The QSM map showed higher sensitivity and especificity for differentiate patients with the disease when compared with controls by the analysis of curve ROC. We conclude that magnetic susceptibility and relaxometry maps may estimate indirect the content of brain iron, although having different dependencies with the concentration of this metal. We also observed that the values of magnetic sususceptibility obtained with low resolution images (1,0 x1, 0x2, 0mm) showed no significant change compared to those obtained with high-resolution images (0,5 x0, 5x2,0mm). So, we suggest the acquisition of images with low resolution to process QSM map. The analysis of multiple relaxation time T2 determined just one value for basal ganglia in both groups, these results were apparently affected by rate noise signal.