RESUMO
Individuals with Parkinson's disease (PD) suffer from motor and mental disturbances due to degeneration of dopaminergic and non-dopaminergic neuronal systems. Although they provide temporary symptom relief, current treatments fail to control motor and non-motor alterations or to arrest disease progression. Aiming to explore safety and possible motor and neuropsychological benefits of a novel strategy to improve the PD condition, a case series study was designed for brain grafting of human neural progenitor cells (NPCs) to a group of eight patients with moderate PD. A NPC line, expressing Oct-4 and Sox-2, was manufactured and characterized. Using stereotactic surgery, NPC suspensions were bilaterally injected into patients' dorsal putamina. Cyclosporine A was given for 10 days prior to surgery and continued for 1 month thereafter. Neurological, neuropsychological, and brain imaging evaluations were performed pre-operatively, 1, 2, and 4 years post-surgery. Seven of eight patients have completed 4-year follow-up. The procedure proved to be safe, with no immune responses against the transplant, and no adverse effects. One year after cell grafting, all but one of the seven patients completing the study showed various degrees of motor improvement, and five of them showed better response to medication. PET imaging showed a trend toward enhanced midbrain dopaminergic activity. By their 4-year evaluation, improvements somewhat decreased but remained better than at baseline. Neuropsychological changes were minor, if at all. The intervention appears to be safe. At 4 years post-transplantation we report that undifferentiated NPCs can be delivered safely by stereotaxis to both putamina of patients with PD without causing adverse effects. In 6/7 patients in OFF condition improvement in UPDRS III was observed. PET functional scans suggest enhanced putaminal dopaminergic neurotransmission that could correlate with improved motor function, and better response to L-DOPA. Patients' neuropsychological scores were unaffected by grafting. Trial Registration: Fetal derived stem cells for Parkinson's disease https://doi.org/10.1186/ISRCTN39104513Reg#ISRCTN39104513.
Assuntos
Mesencéfalo , Células-Tronco Neurais , Doença de Parkinson , Putamen , Adolescente , Adulto , Idoso , Aloenxertos , Dopamina/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Mesencéfalo/metabolismo , Mesencéfalo/patologia , Mesencéfalo/cirurgia , Pessoa de Meia-Idade , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Células-Tronco Neurais/transplante , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/cirurgia , Putamen/metabolismo , Putamen/patologia , Putamen/cirurgiaRESUMO
INTRODUCTION: Cognitive impairment is a prominent feature of schizophrenia that correlates with functional outcome. In the clinical practice and research, there is a need to count on brief, reliable and standardized instruments to evaluate the cognitive profile in psychiatric, geriatric and neurological patients. There are only a few standardized and validated instruments with the Hispanic population, so the adaptation and validation of instruments become a high relevance issue. The Brief Neuropsychological Test in Spanish (NEUROPSI) is a brief neuropsychological battery evaluating a wide spectrum of cognitive functions and standardized with Spanish speaking population according to age and educational level. The purpose of the present study was to determine the sensitivity and specificity of this instrument for its clinical use in patients with schizophrenia, as well as in distinct subtypes of schizophrenic patients: positive, negative and mixed. METHODS: We studied a total sample of 60 subjects (30 patients with schizophrenia and 30 matched controls). Using the total score we found 87.5 % sensitivity and 92.8% specificity. A discriminant analysis using the 25 subtest scores of the NEUROPSI accurately classified 83.3 % of the sample. None of the control subjects was classified as patient. RESULTS: Classification by subtype showed 80 % of patients with negative symptoms, 90 % of patients with positive symptoms and 70 % of patients with mixed symptoms. CONCLUSIONS: The accurate diagnosis of cognitive dysfunction in schizophrenic patients could help in management as well as development of more specific pharmacological treatment for each schizophrenic subtype.
Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Testes Neuropsicológicos , Esquizofrenia/complicações , Esquizofrenia/etnologia , Adulto , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Four cases of transplant to the brain (striatum) of the ventral mesencephalic area (VMA) and three adrenal glands (A) to patients with Parkinson's disease are described as a new alternative for the improvement of this disease. The patients who received VMA showed a very significant improvement in the rigidity, bradykinesia, alterations in walking and posture, as well as the facial expression. Three of the four patients have returned to work. The group that received A tissue, showed a discreet improvement in the rigidity and bradykinesia, but none in the other signs of the disease. These patients are able to accomplish their daily needs, but two are unable to return to work. The differences which we observed between patients receiving VMA and A transplants, might be related to the heterogeneity of the disease, although we believe that the type of graft was responsible of these differences. Our results with the use of VMA, as well as that of other groups, are encouraging, although it is important to clearly establish that it is a procedure which is still in an experimental phase, requiring caution, and should only be practiced in highly qualified centers of clinical research.
Assuntos
Glândulas Suprarrenais/transplante , Transplante de Tecido Encefálico , Transplante de Tecido Fetal , Mesencéfalo/transplante , Doença de Parkinson/cirurgia , Glândulas Suprarrenais/embriologia , Adulto , Idoso , Terapia Combinada , Ciclosporinas/uso terapêutico , Estudos de Avaliação como Assunto , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Mesencéfalo/embriologia , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológicoRESUMO
A 5-item handedness questionnaire was given to 317 subjects in four different groups: (1) 51 Tucano (Amazonian jungle) adolescents (36 male, 15 female); (2) 66 Spanish-speaking adolescents (43 male, 23 female) with similar age and educational background to the Tucano group; (3) 100 urban subjects (50 male, 50 female) with a low educational level; and (4) 100 urban subjects (50 male, 50 female) with a high level of education. Hand preference scores were not affected by sex or educational level. The incidence of left-handedness was lower in the Tucano group than in the other groups, despite the fact that the Tucano culture is a highly permissive one. The two rural groups showed less extreme hand preferences than the urban groups, and the Tucano in particular were less likely to indicate extreme hand preferences on any of the items. These results indicate significant effects of culture and environment on declared hand preference, and may be pertinent to recent discussions of cerebral organization in illiterates.