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1.
J Psychopharmacol ; 35(1): 3-14, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32900259

RESUMO

Dystonia is by far the most intrusive and invalidating extrapyramidal side effect of potent classical antipsychotic drugs. Antipsychotic drug-induced dystonia is classified in both acute and tardive forms. The incidence of drug-induced dystonia is associated with the affinity to inhibitory dopamine D2 receptors. Particularly acute dystonia can be treated with anticholinergic drugs, but the tardive form may also respond to such antimuscarinic treatment, which contrasts their effects in tardive dyskinesia. Combining knowledge of the pathophysiology of primary focal dystonia with the anatomical and pharmacological organization of the extrapyramidal system may shed some light on the mechanism of antipsychotic drug-induced dystonia. A suitable hypothesis is derived from the understanding that focal dystonia may be due to a faulty processing of somatosensory input, so leading to inappropriate execution of well-trained motor programmes. Neuroplastic alterations of the sensitivity of extrapyramidal medium-sized spiny projection neurons to stimulation, which are induced by the training of specific complex movements, lead to the sophisticated execution of these motor plans. The sudden and non-selective disinhibition of indirect pathway medium-sized spiny projection neurons by blocking dopamine D2 receptors may distort this process. Shutting down the widespread influence of tonically active giant cholinergic interneurons on all medium-sized spiny projection neurons by blocking muscarinic receptors may result in a reduction of the influence of extrapyramidal cortical-striatal-thalamic-cortical regulation. Furthermore, striatal cholinergic interneurons have an important role to play in integrating cerebellar input with the output of cerebral cortex, and are also targeted by dopaminergic nigrostriatal fibres affecting dopamine D2 receptors.


Assuntos
Antipsicóticos/farmacologia , Discinesia Induzida por Medicamentos , Distonia , Tratos Extrapiramidais , Interneurônios , Receptores de Dopamina D2/metabolismo , Antagonistas Colinérgicos/uso terapêutico , Neurônios Colinérgicos/efeitos dos fármacos , Neurônios Colinérgicos/fisiologia , Antagonistas dos Receptores de Dopamina D2/farmacologia , Discinesia Induzida por Medicamentos/tratamento farmacológico , Discinesia Induzida por Medicamentos/etiologia , Discinesia Induzida por Medicamentos/metabolismo , Discinesia Induzida por Medicamentos/fisiopatologia , Distonia/induzido quimicamente , Distonia/tratamento farmacológico , Distonia/metabolismo , Distonia/fisiopatologia , Tratos Extrapiramidais/efeitos dos fármacos , Tratos Extrapiramidais/fisiopatologia , Humanos , Interneurônios/efeitos dos fármacos , Interneurônios/fisiologia , Antagonistas Muscarínicos/uso terapêutico , Plasticidade Neuronal
2.
J Neurosci ; 40(30): 5820-5832, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32601242

RESUMO

Following a program of resistance training, there are neural and muscular contributions to the gain in strength. Here, we measured changes in important central motor pathways during strength training in 2 female macaque monkeys. Animals were trained to pull a handle with one arm; weights could be added to increase load. On each day, motor-evoked potentials in upper limb muscles were first measured after stimulation of the primary motor cortex (M1), corticospinal tract (CST), and reticulospinal tract (RST). Monkeys then completed 50 trials with weights progressively increased over 8-9 weeks (final weight ∼6 kg, close to the animal's body weight). Muscle responses to M1 and RST stimulation increased during strength training; there were no increases in CST responses. Changes persisted during a 2 week washout period without weights. After a further 3 months of strength training, an experiment under anesthesia mapped potential responses to CST and RST stimulation in the cervical enlargement of the spinal cord. We distinguished the early axonal volley and later spinal synaptic field potentials, and used the slope of the relationship between these at different stimulus intensities as a measure of spinal input-output gain. Spinal gain was increased on the trained compared with the untrained side of the cord within the intermediate zone and motor nuclei for RST, but not CST, stimulation. We conclude that neural adaptations to strength training involve adaptations in the RST, as well as intracortical circuits within M1. By contrast, there appears to be little contribution from the CST.SIGNIFICANCE STATEMENT We provide the first report of a strength training intervention in nonhuman primates. Our results indicate that strength training is associated with neural adaptations in intracortical and reticulospinal circuits, whereas corticospinal and motoneuronal adaptations are not dominant factors.


Assuntos
Tratos Extrapiramidais/fisiologia , Córtex Motor/fisiologia , Desempenho Psicomotor/fisiologia , Tratos Piramidais/fisiologia , Treinamento de Força/métodos , Animais , Eletrodos Implantados , Macaca mulatta
3.
BMC Med Genet ; 21(1): 77, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293312

RESUMO

BACKGROUND: Myopathy with extrapyramidal signs (MPXPS) is an autosomal recessive mitochondrial disorder which is caused by mutation in mitochondrial calcium uptake 1 (MICU1) gene located on chromosome 10q22.1. Next Generation Sequencing (NGS) technology is the most effective method for identification of pathogenic variants with the ability to overcome some limitations which Sanger sequencing may encountered. There are few reports on this rare disease around the world and here in this study we first revealed genetic identification of two affected individuals in an Iranian family with a novel mutation. CASE PRESENTATION: The proband was a 5-year-old girl from consanguenous parents. She was first clinically suspicious of affected with limb-girdle muscular dystrophy (LGMD). Muscle biopsy studies and autozygosity mapping, using four short tandem repeat (STR) markers linked to 6 genes of the most prevalent forms of LGMD, ruled out calpainopathy, dysferlinopathy, and sarcoglycanopathis. DNA sample of the proband was sent for NGS. Whole exome sequencing (WES) revealed a novel mutation c.1295delA in exon 13 of MICU1 gene. This homozygous deletion creates a frameshift and a premature stop codon downstream of canonical EF4 calcium binding motif of MICU1. According to the American College of Medical Genetics and Genomics (ACMG) guidline for sequence interpretation, this variant was a pathogenic one. Sanger sequencing in all family members confirmed the results of the WES. CONCLUSIONS: This study was the first report of MPXPS in Iranian population which also revealed a novel mutation in the MICU1 gene.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Proteínas de Transporte de Cátions/genética , Repetições de Microssatélites/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , Doenças Musculares/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Pré-Escolar , Exoma/genética , Éxons/genética , Tratos Extrapiramidais/metabolismo , Tratos Extrapiramidais/patologia , Feminino , Mutação da Fase de Leitura/genética , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Irã (Geográfico)/epidemiologia , Doenças Musculares/patologia , Distrofia Muscular do Cíngulo dos Membros/patologia , Linhagem , Deleção de Sequência/genética , Sequenciamento Completo do Exoma
4.
Metab Brain Dis ; 35(5): 829-839, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32212044

RESUMO

Aluminum is a potent neurotoxin used in animal models of neurodegenerative diseases like Alzheimer's disease (AD), in which oxidative stress mediates tissue pathogenesis in vivo. N-acetyl cysteine (NAC) is a glutathione precursor with reported antioxidant and neuroprotective potentials. Recent therapy for combating AD is known to provide only symptomatic relief thus necessitating the discovery of new drugs and their mechanism of action. This study was aimed to demonstrate the in vivo neuroprotective effect of NAC against aluminum (Al3+)-induced neuro-degeneration in rats (a model for AD). Twenty- five (25) adult male Wistar rats used for this study were divided into 5 groups: Group A = Control, B = Aluminum chloride (200 mg/kg), C = 1000 mg/kg of NAC + Aluminum chloride (200 mg/kg), D = 1000 mg/kg of NAC, E = Aluminum chloride (200 mg/kg) was orally administered daily for 3 weeks and discontinued for one week. Frontal Cortex harvested for histological analysis using Haematoxylin and Eosin stain, Cresyl Fast Violet stain for Nissl granules and Glial fibrillary acidic protein immunohistochemistry specific for astrocytes. Aluminum significantly induced oxidative stress, coupled with marked neurons necrosis, chromatolysis and gliosis in the frontal cortex, upon NAC administration, there was neuro anti-inflammatory response as seen in the significant reduction in astrocytes expression, neuronal cell death and Nissl body aggregation which attenuates neuropathological deficits induced by Al3+. It was shown that aluminum is a neurotoxin mediating AD-like oxidative stress, NAC has a therapeutic potential associated with its potent in vivo interaction with astrocytes in response to Al3+ neuro-inflammation seen in positive expression of Nissl granules and glial cells in addition to possibility of endogenous glutathione neuroprotection after withdrawal of stress mediator in neurodegeneration. Graphical abstract.


Assuntos
Acetilcisteína/uso terapêutico , Alumínio , Antioxidantes/uso terapêutico , Tratos Extrapiramidais/patologia , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Córtex Pré-Frontal/patologia , Cloreto de Alumínio/toxicidade , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/tratamento farmacológico , Gliose/patologia , Masculino , Necrose , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
5.
Intern Med ; 58(21): 3163-3165, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292381

RESUMO

A complicated form of spastic paraplegia is a neurodegenerative disorder presenting as progressive spasticity in the bilateral lower limbs accompanied by some clinical features. The present case showed spastic paralysis and hyperreflexia in all extremities as well as lead pipe rigidity in the neck and bilateral upper extremities (R < L), decreased scores on frontal cognitive tests, a decreased accumulation of the right dorsal putamen on a DAT scan, and hypoperfusion of the bilateral frontal lobes on 99mTc-ECD single photon emission computed tomography (SPECT). The present case provides a new spectrum of spastic paraplegia based on the evidence of clinical scores and the findings of brain functional imaging.


Assuntos
Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/complicações , Paraplegia/complicações , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Encéfalo/fisiopatologia , Disfunção Cognitiva/diagnóstico , Tratos Extrapiramidais/diagnóstico por imagem , Tratos Extrapiramidais/fisiopatologia , Lobo Frontal/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Paraplegia/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos
6.
Brain Struct Funct ; 224(5): 1933-1946, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31089853

RESUMO

The laminar organization of the motor cortex of the sheep and other large domestic herbivores received scarce attention and is generally considered homologous to that of rodents and primates. Thickness of the cortex, subdivision into layers and organization are scarcely known. In the present study, we applied different modern morphological, mathematical and image-analyses techniques to the study of the motor area that controls movements of the forelimb in the sheep. The thickness of the cortex resulted comparable to that of other terrestrial Cetartiodactyls (but thicker than in marine Cetartiodactyls of similar body mass). The laminar organization showed marked development of layer 1, virtual absence of layer 4, and image analysis suggested prevalence of large irregular neural cells in the deeper layers. Diffusion tensor imaging revealed robust projections from the motor cortex to the pyramids in the brainstem, and well evident tracts descending to the tegmentum of the mesencephalon and dorsal pons. Our data contrast the general representation of the motor system of this species, considered to be predominantly based on extra-pyramidal tracts that originate from central pattern generators in the brainstem.


Assuntos
Tronco Encefálico/anatomia & histologia , Tratos Extrapiramidais/anatomia & histologia , Membro Anterior/anatomia & histologia , Córtex Motor/anatomia & histologia , Animais , Mapeamento Encefálico/métodos , Imagem de Tensor de Difusão/métodos , Neurônios/patologia , Ovinos
7.
Neurorehabil Neural Repair ; 33(5): 375-383, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30913964

RESUMO

BACKGROUND: Recent evidence from both monkey and human studies suggests that the reticulospinal tract may contribute to recovery of arm and hand function after stroke. In this study, we evaluated a marker of reticulospinal output in stroke survivors with varying degrees of motor recovery. METHODS: We recruited 95 consecutive stroke patients presenting 6 months to 12 years after their index stroke, and 19 heathy control subjects. Subjects were asked to respond to a light flash with a rapid wrist flexion; at random, the flash was paired with either a quiet or loud (startling) sound. The mean difference in electromyogram response time after flash with quiet sound compared with flash with loud sound measured the StartReact effect. Upper limb function was assessed by the Action Research Arm Test (ARAT), spasticity was graded using the Modified Ashworth Scale (MAS) and active wrist angular movement using an electrogoniometer. RESULTS: StartReact was significantly larger in stroke patients than healthy participants (78.4 vs 45.0 ms, P < .005). StartReact showed a significant negative correlation with the ARAT score and degree of active wrist movement. The StartReact effect was significantly larger in patients with higher spasticity scores. CONCLUSION: We speculate that in some patients with severe damage to their corticospinal tract, recovery led to strengthening of reticulospinal connections and an enhanced StartReact effect, but this did not occur for patients with milder impairment who could use surviving corticospinal connections to mediate recovery.


Assuntos
Tratos Extrapiramidais/fisiopatologia , Espasticidade Muscular/fisiopatologia , Reflexo de Sobressalto/fisiologia , Formação Reticular/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Extremidade Superior/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Stroke ; 49(12): 2928-2932, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30571408

RESUMO

Background and Purpose- Tractography by diffusion tensor imaging has extended our knowledge on the contribution of damage to different pathways to residual motor function after stroke. Integrity of the corticospinal tract (CST), for example, has been identified to characterize and predict its course. Yet there is only scarce data that allow a judgment on the impact of extrapyramidal pathways between the basal ganglia on motor function poststroke. We aimed at studying their association with performance in fine motor skills after stroke. Methods- We performed probabilistic tractography and reconstructed nigro-pallidal tracts connecting substantia nigra and globus pallidus, as well as the CST in 26 healthy subjects. Resulting tracts were registered to the individual images of 20 patients 3 months after stroke, and their microstructural integrity was measured by fractional anisotropy. Clinical examination of the patients' gross (grip force) and fine (nine-hole peg test) motor skills was performed 1 year after stroke. For assessment of factors influencing nine-hole peg test, we used a multivariate model. Results- Nigro-pallidal tracts were traceable in all participants, had no overlap to the CST and passed the nucleus subthalamicus. In stroke patients, nigro-pallidal tracts ipsilateral to the stroke lesion showed a significantly reduced fractional anisotropy (ratio, 0.96±0.02; P=0.021). One year after stroke, nine-hole peg test values were significantly slower for the affected hand, while grip force was comparable between both hands. Reduced integrity of the nigro-pallidal tracts was associated with worse performance in the nine-hole peg test ( P=0.040), as was reduced integrity of the CST ( P<0.001) and younger age ( P<0.001). Conclusions- Nigro-pallidal tracts with containing connections of the nucleus subthalamicus represent a relevant part of the extrapyramidal system and specifically contribute to residual fine motor skills after stroke beyond the well-known contribution of the CST. They may deliver supportive information for prediction of motor recovery after stroke.


Assuntos
Tratos Extrapiramidais/diagnóstico por imagem , Destreza Motora/fisiologia , Tratos Piramidais/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Imagem de Tensor de Difusão , Feminino , Globo Pálido/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Vias Neurais/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
9.
Exp Brain Res ; 236(10): 2611-2618, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29961087

RESUMO

We studied the short-latency (SL) effects of postural perturbations produced by impulses applied over the spine of the C7 vertebra or the sternum ("axial impulses") in 12 healthy subjects. EMG recordings were made bilaterally from the triceps brachii, biceps brachii, soleus, and tibialis anterior muscles, and unilaterally from the deltoid, forearm flexors, forearm extensors, and first dorsal interosseous (FDI) muscles. Sternal impulses evoked short-latency responses in the biceps when subjects leaned posteriorly to support approximately 12% of their body weight with the arms, but these responses were only modestly larger than for isometric contraction of the arms (26.3 vs. 14.7%). In contrast, clear excitatory responses could be evoked in the deltoid, triceps, forearm muscles, and FDI when leaning anteriorly to support similar amounts of body weight. These responses were significantly larger than during isometric contraction. The deltoid (42.5%) and triceps (44.7%) had the largest responses in supported anterior lean and onset latencies increased distally in this condition (mean 31.8 ms in deltoid to 53.7 ms in FDI). There was a disproportionate delay between the forearm muscles and FDI. For both directions of lean, postural reflex responses normally present in the legs were severely attenuated. SL upper limb excitatory responses were bigger in proximal muscles as well as larger and more widespread for anterior axial perturbations compared to posterior axial perturbations when using the arms to support body weight. Our findings also provide further evidence of a role for reticulospinal pathways in mediating these rapid postural responses to accelerations of the trunk.


Assuntos
Tratos Extrapiramidais/fisiologia , Contração Isométrica/fisiologia , Músculo Esquelético/fisiologia , Tempo de Reação/fisiologia , Reflexo/fisiologia , Extremidade Superior/fisiologia , Adolescente , Eletromiografia , Feminino , Humanos , Masculino , Propriocepção , Psicofísica , Adulto Jovem
10.
BMJ Open ; 7(5): e014938, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28550022

RESUMO

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis. In this context, we propose a longitudinal study of a cohort of SCZ and schizophrenic and schizoaffective disorder (SAD) Sardinian patients with the aim of disentangling the relationship between peripheral BDNF serum levels and changes of psychopathology, cognition and drug treatments. METHODS AND ANALYSIS: Longitudinal assessment of BDNF in Sardinian psychotic patients (LABSP) is a 24-month observational prospective cohort study. Patients with SAD will be recruited at the Psychiatry Research Unit of the Department of Medical Science and Public Health, University of Cagliari and University of Cagliari Health Agency, Cagliari, Italy. We will collect BDNF serum levels as well as sociodemographic, psychopathological and neurocognitive measures. Structured, semistructured and self-rating assessment tools, such as the Positive and Negative Syndrome Scale for psychopathological measures and the Brief Assessment of Cognition in Schizophrenia for cognitive function, will be used. ETHICS AND DISSEMINATION: This study protocol was approved by the University of Cagliari Health Agency Ethics Committee (NP2016/5491). The study will be conducted in accordance with the principles of good clinical practice, in the Declaration of Helsinki in compliance with the regulations. Participation will be voluntary and written informed consent will be obtained for each participant upon entry into the study. We plan to disseminate the results of our study through conference presentations and publication in international peer-reviewed journals. Access to raw data will be available in anonymised form upon request to the corresponding author.


Assuntos
Antipsicóticos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/sangue , Cognição/fisiologia , Transtornos Psicóticos/sangue , Transtornos Psicóticos/tratamento farmacológico , Adulto , Biomarcadores/sangue , Protocolos Clínicos , Cognição/efeitos dos fármacos , Tratos Extrapiramidais/fisiopatologia , Feminino , Humanos , Itália , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prognóstico , Estudos Prospectivos , Transtornos Psicóticos/fisiopatologia , Índice de Gravidade de Doença , Adulto Jovem
11.
Acta Odontol Scand ; 75(3): 220-226, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28116993

RESUMO

OBJECTIVE: The study explores the association between severity of illness (positive, negative, depressive and cognitive symptoms) and extra pyramidal symptoms (EPS) with dental caries, periodontal disease and prosthetic needs among patients with schizophrenia. MATERIAL AND METHODS: A total of 71 schizophrenic patients diagnosed based on ICD-10 criteria participated in the study. Clinical Global Impression - Schizophrenia (CGI-SCH) scale was used to evaluate positive, negative, depressive, cognitive symptoms and overall severity of schizophrenia. Simpson-Angus Scale (SAS) was used for assessment of EPS. Dental examinations were conducted as per WHO (1997) criterion. RESULTS: Mean DMFT and CPI scores with periodontal pockets were 5.57 ± 2.12 and 2.37 ± 0.74; significant differences being noted among those with and without EPS (p < 0.001). Positive and EPS associated with dental caries with odds ratio of 5.26 (1.05, 26.2) and 8.52 (2.31, 31.4) (p < 0.001). Depressive and EPS were associated with periodontal disease with odds ratio of 4.19 (1.53, 32.5) and 5.27 (1.29, 21.5), respectively (p < 0.001). Cognitive and EPS were associated with dental prosthetic needs with odds ratio of 4.33 (1.47, 31.2) (p < 0.001) and 7.78 (1.43, 42.2), respectively (p < 0.001). CONCLUSIONS: Patients with schizophrenia had high dental caries, periodontal disease and unmet dental prosthetic needs. Severity of the schizophrenic and EPS was associated with poor oral health. Efforts need to be focused on strengthening the evidence of its association with oral health indicators through further studies including cohort investigations.


Assuntos
Cárie Dentária/etiologia , Tratos Extrapiramidais/fisiopatologia , Saúde Bucal/estatística & dados numéricos , Doenças Periodontais/etiologia , Esquizofrenia/complicações , Adulto , Assistência Odontológica/estatística & dados numéricos , Cárie Dentária/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Periodontais/diagnóstico , Índice de Gravidade de Doença
12.
Eur J Clin Pharmacol ; 73(3): 351-355, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27889833

RESUMO

PURPOSE: The aim of this study was to investigate factors associated with the occurrence of extrapyramidal symptoms (EPS) in users of second-generation antipsychotics (SGA). METHODS: Observational cross-sectional study based on a random sample of subjects from three outpatient clinics. Inclusion criteria were age between 18 and 65 years, of both genders, with a diagnosis of schizophrenia and under the use of a single SGA agent. Subjects who had received i.m. long-acting antipsychotics in the past were excluded. The families of eligible patients were contacted by phone and, if willing to participate in the study, a household visit was scheduled. Informed consent was obtained from all study subjects and their next of kin. The risk of EPS associated with sociodemographic, clinical features and medications used was analyzed by logistic regression. RESULTS: The study population consisted of 213 subjects. EPS were observed in 38.0% of subjects. The more commonly used SGA were olanzapine (76, 35.7%), risperidone (74, 34.3%), quetiapine (26, 12.2%), and ziprasidone (23, 10.8%). Among the drugs used as adjunctive therapy for schizophrenia, benzodiazepines were the most prevalent (31.5%), followed by carbamazepine (24.4%) and antidepressants (20.2%). Multivariate analysis showed that the risk of EPS was associated with the use of carbamazepine (odds ratio 3.677, 95% CI 1.627-8.310). We found no evidence that the type of SGA modified the risk of EPS. CONCLUSION: The occurrence of EPS in SGA users is a common finding, with no difference of antipsychotics studied in relation to the risk of extrapyramidal manifestations. The adjunctive use of carbamazepine may predispose the user of SGA to the occurrence of EPS.


Assuntos
Antipsicóticos/efeitos adversos , Tratos Extrapiramidais/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Clin J Pain ; 33(7): 635-639, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27623111

RESUMO

OBJECTIVE: Pain is one of the most common nonmotor symptoms of Parkinson disease (PD) and other Parkinson plus syndromes, with a major effect on quality of life. The aims of the study were to examine the prevalence and characteristics of pain in PD and other Parkinson plus syndromes and patient use and response to pain medications. METHODS: The cohort consisted of 371 patients: 300 (81%) with PD and 71 (19%) with Parkinson plus syndromes. Data on clinical parameters and pain were collected by questionnaire. Disease severity was measured with the Unified PD Rating Scale for patients with PD. RESULTS: Pain was reported by 277 patients (74%): 241 with PD and 36 with Parkinson plus syndromes. The prevalence of pain was significantly higher in the patients with PD than in the patients with Parkinson plus syndromes (80% vs. 50%, P<0.001) and higher in patients with synucleinopathies than in patients with tauopathies (70% vs. 40%, P<0.001). In the synucleinopathies, the most common pain was central pain (32%), whereas in the tauopathies only 4% of patients had central pain. Anti-Parkinson treatment relieved the pain in 21% of the patients with PD. Only 114 patients (48%) who experienced pain were treated with pain medications. The most beneficial analgesics were nonsteroidal anti-inflammatory drugs and medical cannabis. CONCLUSION: Pain is prevalent among patients with PD and Parkinsonian plus syndromes. Pain relief can be achieved by more intensive anti-Parkinson medications or pain medications.


Assuntos
Tratos Extrapiramidais/patologia , Atrofia de Múltiplos Sistemas/complicações , Dor/etiologia , Doença de Parkinson/complicações , Paralisia Supranuclear Progressiva/complicações , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/classificação , Dor/diagnóstico , Manejo da Dor , Medição da Dor , Índice de Gravidade de Doença , Inquéritos e Questionários
14.
Med Hypotheses ; 87: 14-21, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26826634

RESUMO

The introduction of selective serotonin reuptake inhibitors has gradually changed the borders of the major depression disease class. Anhedonia was considered a cardinal symptom of endogenous depression, but the potential of selective serotonin reuptake inhibitors to treat anxiety disorders has increased the relevance of stress-induced morbidity. This shift has led to an important heterogeneity of current major depressive disorder. The complexity can be disentangled by postulating the existence of two different but mutually interacting neuronal circuits regulating the intensity of anhedonia (lack of pleasure) and dysphoria (lack of happiness). These circuits are functionally dominated by partly closed limbic (regulating misery-fleeing behaviour) and extrapyramidal (regulating reward-seeking behaviour) cortico-striato-thalamo-cortical (CSTC) circuits. The re-entry circuits include the shell and core parts of the accumbens nucleus, respectively. Pleasure can be considered to result from finding relief from the hypermotivation to exhibit rewarding behaviour, and happiness from finding relief from negative or conflicting circumstances. Hyperactivity of the extrapyramidal CSTC circuit results in craving, whereas hyperactivity of the limbic system results in dysphoria.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Felicidade , Prazer/fisiologia , Transtorno Depressivo Maior/tratamento farmacológico , Tratos Extrapiramidais/fisiopatologia , Humanos , Sistema Límbico/fisiopatologia , Modelos Neurológicos , Modelos Psicológicos , Vias Neurais/fisiopatologia , Inibidores de Captação de Serotonina/uso terapêutico
15.
Neurosci Lett ; 606: 36-41, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-26342496

RESUMO

This study aimed to examine the functional networks related to the extrapyramidal system using a temporal oscillation signal correlation analysis method based on critical nodes in the substantia nigra (SN), red nucleus (RN) and dentate nucleus (DN). Nineteen healthy subjects underwent resting-state fMRI and susceptibility weighted imaging (SWI). For the brain network analysis, the SN, RN and DN were positioned on susceptibility weighted images and used as seeds for temporal correlations analyzed via BOLD data. T-tests were performed for the correlation coefficients of each seed. We demonstrated that the SN, RN and DN were functionally connected to each other, and, in general, their connectivity maps overlapped in a series of subcortical extrapyramidal structures and regions of cerebral cortices. A Granger causality analysis indicated that the effective connectivity graphs within extrapyramidal structures mainly exhibited a spacial up-down pattern for the positive and negative influences, respectively. Our findings suggest that extensive regions involved in the extrapyramidal system constituted a relatively exclusive network via spatial-temporal correlation signals that analogously corresponded to the anatomical structures. The investigation of extrapyramidal system networks may have potential clinical implications.


Assuntos
Núcleos Cerebelares/fisiologia , Tratos Extrapiramidais/fisiologia , Núcleo Rubro/fisiologia , Substância Negra/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
17.
Ann Pharmacother ; 49(10): 1136-52, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26185277

RESUMO

OBJECTIVE: Extrapyramidal reactions (EPRs) associated with serotonergic antidepressant treatments have been reported since 1958. These reactions can be distressing for patients and complicate treatment. Our objective was to complete a follow-up review of published EPR cases reported for serotonergic antidepressants. DATA SOURCES: Published cases between January 1998 and May 2015 were collected through a medical literature search. Citation reference lists were also searched manually. STUDY SELECTION AND DATA EXTRACTION: Identified cases were reviewed for patient age, gender, psychiatric diagnosis, dosage, time to reaction onset, concurrent medications, and EPR description. Cases were excluded when there was not a clear description, if descriptions were not consistent with accepted definitions, or if the written English was poor. We included cases of akathisia, dystonia, dyskinesia, parkinsonism, or mixed EPRs. Authors scored each case using the Naranjo adverse drug reaction probability scale. DATA SYNTHESIS: We identified 86 published reports involving 91 patients; selective serotonin reuptake inhibitors were implicated in 80.2% of cases. All EPR types were reported: 17 akathisia cases, 18 dyskinesia cases, 27 dystonia cases, 19 parkinsonism cases, and 10 mixed EPR cases. EPRs typically occurred within 30 days of either treatment initiation or dose increase. Age, gender, antidepressant dosing, or concurrent antipsychotic treatment did not appear to broadly contribute to EPR risk. Naranjo scores ranged from 2 to 8. CONCLUSIONS: Case reports associating serotonergic antidepressants with EPRs continue to be published. Practitioners are advised that monitoring for such is important. Rigorous research efforts are needed to better understand the clinical risk factors for these adverse drug reactions.


Assuntos
Antidepressivos/efeitos adversos , Tratos Extrapiramidais/efeitos dos fármacos , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores da Captação Adrenérgica/efeitos adversos , Fatores Etários , Acatisia Induzida por Medicamentos/etiologia , Acatisia Induzida por Medicamentos/fisiopatologia , Antipsicóticos/efeitos adversos , Discinesia Induzida por Medicamentos/etiologia , Discinesia Induzida por Medicamentos/fisiopatologia , Tratos Extrapiramidais/fisiopatologia , Feminino , Humanos , Masculino , Doença de Parkinson Secundária/etiologia , Doença de Parkinson Secundária/fisiopatologia , Agitação Psicomotora/tratamento farmacológico , Fatores de Risco , Fatores Sexuais
18.
Neurosurg Rev ; 38(4): 739-50; discussion 751, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25962557

RESUMO

Recent advances in imaging permit radiologic identification of target structures for deep brain stimulation (DBS) for movement disorders. However, these methods cannot detect the internal subdivision and thus cannot determine the appropriate DBS target located within those subdivisions. The aim of this study is to provide a straightforward method to obtain an optimized target (OT) within DBS target nuclei using a widely available navigation system. We used T1- and T2-weighted images, fluid-attenuated inversion recovery (FLAIR) sequence, and diffusion tensor imaging (DTI) of nine patients operated for DBS in our center. Using the StealthViz® software, we segmented the targeted deep structures (subcortical targets) and the anatomically identifiable areas to which these target nuclei were connected (projection areas). We generated fiber tracts from the projection areas. By identifying their intersections with the subcortical targets, we obtained an OT within the DBS target nuclei. We computed the distances from the clinically effective electrode contacts (CEEC) to the OT obtained by our method and the targets provided by the atlas. These distances were compared using a Wilcoxon signed-rank test, with p < 0.05 considered statistically significant. We were able to identify OT coincident with the motor part of the subthalamic nucleus and the ventral intermediate nucleus. We clinically tested the results and found that the CEEC were significantly more closely related to the OT than with the targets obtained by the atlas. Our present results show that this novel method permits optimization of the stimulation site within the internal subdivisions of target nuclei for DBS.


Assuntos
Estimulação Encefálica Profunda/métodos , Imagem de Tensor de Difusão/métodos , Neuronavegação/métodos , Procedimentos Neurocirúrgicos/métodos , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Atlas como Assunto , Gânglios da Base/anatomia & histologia , Gânglios da Base/cirurgia , Eletrodos , Tremor Essencial/terapia , Tratos Extrapiramidais/anatomia & histologia , Tratos Extrapiramidais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/terapia , Software , Técnicas Estereotáxicas
19.
Exp Neurol ; 266: 112-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25666586

RESUMO

The corticospinal and rubrospinal tracts are the predominant tracts for controlling skilled hand function. Injuries to these tracts impair grasping but not gross motor functions such as overground locomotion. The aim of the present study was to determine whether or not, after damage to both the corticospinal and rubrospinal tracts, other spared subcortical motor pathway can mediate the recovery of skilled hand function. Adult rats received a bilateral injury to the corticospinal tract at the level of the medullar pyramids and a bilateral ablation of the rubrospinal axons at C4. One group of rats received, acutely after injury, two injections of chondroitinase-ABC at C7, and starting at 7days post-injury were enrolled in daily reaching and grasping rehabilitation (CHASE group, n=5). A second group of rats received analogous injections of ubiquitous penicillinase, and did not undergo rehabilitation (PEN group, n=5). Compared to rats in the PEN group, CHASE rats gradually recovered the ability to reach and grasp over 42days after injury. Overground locomotion was mildly affected after injury and both groups followed similar recovery. Since the reticulospinal tract plays a predominant role in motor control, we further investigated whether or not plasticity of this pathway could contribute to the animal's recovery. Reticulospinal axons were anterogradely traced in both groups of rats. The density of reticulospinal processes in both the normal and ectopic areas of the grey ventral matter of the caudal segments of the cervical spinal cord was greater in the CHASE than PEN group. The results indicate that after damage to spinal tracts that normally mediate the control of reaching and grasping in rats other complementary spinal tracts can acquire the role of those damaged tracts and promote task-specific recovery.


Assuntos
Tratos Extrapiramidais/lesões , Tratos Extrapiramidais/fisiopatologia , Membro Anterior/fisiopatologia , Destreza Motora , Vias Neurais/fisiopatologia , Plasticidade Neuronal , Tratos Piramidais/lesões , Tratos Piramidais/fisiopatologia , Recuperação de Função Fisiológica , Animais , Feminino , Força da Mão , Locomoção , Desempenho Psicomotor , Ratos , Ratos Long-Evans
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