RESUMEN
BACKGROUND: Mild cognitive impairment (MCI) is a common feature of isolated rapid-eye-movement sleep behavior disorder (iRBD). Here, we assessed cognitive functions and MCI in a prospective iRBD cohort and investigated their association with disease-specific brain metabolic patterns. METHODS: Forty-four patients with polysomnography-confirmed iRBD performed a standardized battery of neuropsychological examinations every two years. We used previously established spatial covariance patterns from de novo drug-naïve Parkinson's disease with concomitant RBD (denovoPDRBD-RP) and iRBD (iRBD-RP) using 18F-fluorodeoxyglucose PET scan. We compared those expressions between iRBD with normal cognition (iRBD-NC) and with mild cognitive impairment (iRBD-MCI), and evaluated whether they predict progressive cognitive deterioration. RESULTS: Twenty iRBD patients (45 %) had MCI at baseline and 12 patients (27 %, about 7 % per year) had clinically significant cognitive deterioration after 4 years. The iRBD-MCI and iRBD-NC groups showed similar rates of cognitive change, but iRBD-MCI consistently performed worse in the domains of verbal memory and executive function. Elevated denovoPDRBD-RP expression predicted cognitive deterioration (hazard ratio = 5.98 [1.70-21.06]), whereas iRBD-RP did not. CONCLUSIONS: Increased disease-specific brain metabolic patterns are associated with iRBD-MCI and impending cognitive deterioration with the risk of progression to Lewy body dementia.
Asunto(s)
Encefalopatías Metabólicas/psicología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/psicología , Trastorno de la Conducta del Sueño REM/metabolismo , Trastorno de la Conducta del Sueño REM/psicología , Anciano , Encéfalo/metabolismo , Función Ejecutiva/fisiología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Memoria/fisiología , Persona de Mediana Edad , Polisomnografía , Tomografía de Emisión de Positrones , Radiofármacos , Conducta Verbal/fisiologíaRESUMEN
BACKGROUND: Glutaric aciduria type I (GA-I) is an inherited metabolic disease due to deficiency of glutaryl-CoA dehydrogenase (GCDH). Cognitive functions are generally thought to be spared, but have not yet been studied in detail. METHODS: Thirty patients detected by newborn screening (n = 13), high-risk screening (n = 3) or targeted metabolic testing (n = 14) were studied for simple reaction time (SRT), continuous performance (CP), visual working memory (VWM), visual-motor coordination (Tracking) and visual search (VS). Dystonia (n = 13 patients) was categorized using the Barry-Albright-Dystonia Scale (BADS). Patients were compared with 196 healthy controls. Developmental functions of cognitive performances were analysed using a negative exponential function model. RESULTS: BADS scores correlated with speed tests but not with tests measuring stability or higher cognitive functions without time constraints. Developmental functions of GA-I patients significantly differed from controls for SRT and VS but not for VWM and showed obvious trends for CP and Tracking. Dystonic patients were slower in SRT and CP but reached their asymptote of performance similar to asymptomatic patients and controls in all tests. Asymptomatic patients did not differ from controls, except showing significantly better results in Tracking and a trend for slower reactions in visual search. Data across all age groups of patients and controls fitted well to a model of negative exponential development. CONCLUSIONS: Dystonic patients predominantly showed motor speed impairment, whereas performance improved with higher cognitive load. Patients without motor symptoms did not differ from controls. Developmental functions of cognitive performances were similar in patients and controls. Performance in tests with higher cognitive demand might be preserved in GA-I, even in patients with striatal degeneration.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/psicología , Encefalopatías Metabólicas/psicología , Trastornos del Conocimiento/psicología , Distonía/psicología , Glutaril-CoA Deshidrogenasa/deficiencia , Pruebas Neuropsicológicas , Adaptación Psicológica , Adolescente , Adulto , Niño , Conducta Infantil , Preescolar , Estudios Transversales , Procesamiento Automatizado de Datos , Femenino , Humanos , Recién Nacido , Masculino , Tamizaje Neonatal , Adulto JovenAsunto(s)
Disfunción Cognitiva/etiología , Hipocalcemia/etiología , Hipoparatiroidismo/etiología , Esclerodermia Sistémica/complicaciones , Encefalopatías Metabólicas/diagnóstico por imagen , Encefalopatías Metabólicas/etiología , Encefalopatías Metabólicas/psicología , Calcinosis/diagnóstico por imagen , Calcinosis/etiología , Calcinosis/psicología , Calcio/uso terapéutico , Comorbilidad , Humanos , Hipocalcemia/tratamiento farmacológico , Hipotiroidismo/complicaciones , Hipotiroidismo/tratamiento farmacológico , Aneurisma Intracraneal/complicaciones , Masculino , Cumplimiento de la Medicación , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Polifarmacia , Esclerodermia Sistémica/psicología , Tiroxina/uso terapéutico , Tomografía Computarizada por Rayos X , Vitamina D/análogos & derivados , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
Effects of pirebedil used to prevent falls in elderly patients with metabolic syndrome are discussed. A prospective controlled study showed that therapy with pirebedil significantly decreases the frequency of falls, reduces severity of pro-inflammatory and pro-oxidative activities, improves cognitive abilities. Prevention of falls by virtue of improved cognitive abilities is a new clinical effect of pirebedil and gives reason to recommend it for the treatment of geriatric patients with metabolic syndrome.
Asunto(s)
Accidentes por Caídas/prevención & control , Encefalopatías Metabólicas , Diabetes Mellitus Tipo 2 , Competencia Mental , Piribedil , Anciano , Encefalopatías Metabólicas/tratamiento farmacológico , Encefalopatías Metabólicas/etiología , Encefalopatías Metabólicas/fisiopatología , Encefalopatías Metabólicas/psicología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/farmacocinética , Femenino , Evaluación Geriátrica/métodos , Humanos , Masculino , Persona de Mediana Edad , Nootrópicos/administración & dosificación , Nootrópicos/farmacocinética , Piribedil/administración & dosificación , Piribedil/farmacocinética , Estudios Prospectivos , Resultado del TratamientoRESUMEN
PURPOSE: The case of a patient with Parkinson's disease (PD) who experienced profound encephalopathy after short-term exposure to metoclopramide is described. SUMMARY: A 79-year-old man with PD received metoclopramide (10 mg i.v. every six hours) for stimulation of gastric motility after a colon resection; the first of three doses of the drug was administered about 30 minutes after completion of the afternoon procedure. The evening after surgery, the patient appeared to be resting comfortably without pain, although he was somewhat agitated; two more metoclopramide doses were administered during the night. Over the next several hours his mental status deteriorated, and the next morning he was found to be unresponsive and could not be aroused. Although the patient had received minimal narcotics, naloxone was administered but failed to produce an improvement in the patient's mental status. The results of laboratory tests, computer tomography scanning, and other diagnostic studies ruled out cardiac ischemia, infectious disease, and other potential causes of the abrupt change in mental status. Within eight days of the discontinuation of metoclopramide use, the patient gradually returned to his baseline mental status. The application of the algorithm of Naranjo et al. in this case indicated a possible adverse reaction to metoclopramide as the cause of acute metabolic encephalopathy, with the patient's underlying PD and PD-related dementia suspected to have been contributing factors. CONCLUSION: A 79-year-old man with long-term PD developed acute encephalopathy after the administration of i.v. metoclopramide.
Asunto(s)
Encefalopatías Metabólicas/inducido químicamente , Encefalopatías Metabólicas/diagnóstico , Metoclopramida/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Encefalopatías Metabólicas/psicología , Humanos , Masculino , Enfermedad de Parkinson/psicologíaAsunto(s)
Encefalopatías Metabólicas , Hiperamonemia , Trastornos Psicóticos/tratamiento farmacológico , Ácido Valproico , Amoníaco/sangre , Antimaníacos/administración & dosificación , Antimaníacos/efectos adversos , Encefalopatías Metabólicas/sangre , Encefalopatías Metabólicas/etiología , Encefalopatías Metabólicas/psicología , Encefalopatías Metabólicas/terapia , Femenino , Humanos , Hiperamonemia/sangre , Hiperamonemia/inducido químicamente , Hiperamonemia/complicaciones , Persona de Mediana Edad , Resultado del Tratamiento , Ácido Valproico/administración & dosificación , Ácido Valproico/efectos adversos , Privación de TratamientoRESUMEN
Patients with hepatitis C virus (HCV) infection frequently show neuropsychiatric symptoms. This study aims to help clarify the neurochemical mechanisms behind these symptoms and to add further proof to the hypothesis that HCV may affect brain function. Therefore, 15 patients who reported increasing chronic fatigue, mood alterations, and/or cognitive decline since their HCV infection underwent neurologic and neuropsychological examination, magnetic resonance imaging, (18)F-fluoro-deoxy-glucose positron emission tomography of the brain, and single photon emission tomography of striatal dopamine and midbrain serotonin transporter (SERT) availability. None of the patients had liver cirrhosis. Patients' data were compared with data of age-matched controls. In addition, regression analysis was performed between cognitive deficits, and mood and fatigue scores as dependent variables, and cerebral glucose metabolism, dopamine, or SERT availability as predictors. Patients showed significant cognitive deficits, significantly decreased striatal dopamine and midbrain SERT availability, and significantly reduced glucose metabolism in the limbic association cortex, and in the frontal, parietal, and superior temporal cortices, all of which correlated with dopamine transporter availability and psychometric results. Thus, the study provides further evidence of central nervous system affection in HCV-afflicted patients with neuropsychiatric symptoms. Data indicate alteration of dopaminergic neurotransmission as a possible mechanism of cognitive decline.
Asunto(s)
Encefalopatías Metabólicas/metabolismo , Encéfalo/metabolismo , Glucosa/metabolismo , Hepatitis C/complicaciones , Encefalopatías Metabólicas/diagnóstico por imagen , Encefalopatías Metabólicas/etiología , Encefalopatías Metabólicas/psicología , Cognición/fisiología , Dopamina/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Hepatitis C/diagnóstico por imagen , Hepatitis C/metabolismo , Humanos , Batería Neuropsicológica de Luria-Nebraska , Memoria/fisiología , Tomografía de Emisión de Positrones , Radiofármacos , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Ketogenic diet is a nonpharmacologic treatment for childhood epilepsy not amenable to drugs. At the present time, two works based on national research, one in Germany and one in the United States provide international guidelines to ensure a correct management of the ketogenic diet. Our Italian collaborative study group was set up in order to formulate a consensus statement regarding the clinical management of the ketogenic diet, patient selection, pre-ketogenic diet, counseling, setting and enforcement of dietary induction of ketosis, follow-up management, and eventual discontinuation of the diet.
Asunto(s)
Dieta Cetogénica/métodos , Epilepsias Mioclónicas/dietoterapia , Epilepsias Mioclónicas/psicología , Educación del Paciente como Asunto/métodos , Encefalopatías Metabólicas/dietoterapia , Encefalopatías Metabólicas/metabolismo , Encefalopatías Metabólicas/psicología , Consenso , Epilepsias Mioclónicas/metabolismo , Estudios de Seguimiento , Humanos , Italia , SíndromeAsunto(s)
Adaptación Psicológica , Trastornos de la Conducta Infantil/psicología , Conducta Cooperativa , Discapacidades del Desarrollo/psicología , Comunicación Interdisciplinaria , Errores Innatos del Metabolismo/psicología , Grupo de Atención al Paciente , Adolescente , Trastorno Autístico/psicología , Encefalopatías Metabólicas/psicología , Niño , Preescolar , Comorbilidad , Francia , Humanos , Lactante , Relaciones Profesional-FamiliaAsunto(s)
Trastornos de la Conducta Infantil/diagnóstico , Trastornos de la Conducta Infantil/psicología , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/psicología , Trastornos Neurocognitivos/diagnóstico , Adolescente , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/psicología , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/psicología , Niño , Preescolar , Diagnóstico Diferencial , Proteínas en la Dieta/metabolismo , Humanos , Lactante , Adulto JovenRESUMEN
Degeneration of cholinergic receptors causes memory disorders and irreversible impairment in cognitive functions, whose advancement can lead to clinically recognizable Alzheimer's disease (AD). Very often, the first symptoms of AD are mood swings and hence depression should be excluded by differential diagnosis since it can also cause memory disorders and cognitive deficits. Due to the characteristic clinical picture of AD, its diagnosis should not be a problem, except at the very beginning of the disease. Many AD patients are never diagnosed and therefore are not adequately treated in clinical practice. Agents used for general anaesthesia reduce cholinergic transmission, which is manifested by loss of consciousness, pain, voluntary movements and memory. In patients with compromised memory and cognitive functionality, general anaesthesia can postoperatively have an adverse effect on the prognosis of degenerative cerebral disease. A patient is described whose preoperative impaired memory and cognitive functioning deteriorated after general anaesthesia and whose clinical picture reached the extent of AD.
Asunto(s)
Enfermedad de Alzheimer/inducido químicamente , Anestesia General/efectos adversos , Encefalopatías Metabólicas/inducido químicamente , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/psicología , Diagnóstico Diferencial , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Glutaric aciduria type I (GA I) is an autosomal recessive disorder of lysine and tryptophan metabolism due to a deficiency in glutaryl-CoA dehydrogenase activity. Recent reports suggest that early diagnosis through newborn screening and initiation of preventive therapy result in improved functional outcome; however, detailed neuropsychological profiles of children with GA I are seldom reported and thus the impact of the disease on cognition, motor abilities and behaviour remains uncertain. METHOD: We present detailed neuropsychological profiles of three children who were diagnosed with GA I through newborn screening and treated from early age, and one asymptomatic patient diagnosed through cascade screening. A comprehensive battery of standardized tests was administered including measures of intellectual function, attention/memory, executive function, motor skills, speech/language, as well as behavioural and adaptive skills. RESULTS: The results reveal overall average cognitive outcomes; however, subtle, but significant, fine motor and articulation deficits were observed. The results are discussed with regard to potential links between fine motor deficits and speech impairments in children with GA I. Such difficulties can impact on the child's ability to engage in academic, leisure and daily activities. CONCLUSIONS: These findings highlight the importance of in-depth assessments of all aspects of neuropsychological function in patients with GA I and provide a basis for future neuropsychological assessment in similar groups of children. In spite of relatively preserved overall functioning, using a broad range of sensitive cognitive and motor measures facilitates the detection of subtle deficits, and allows for planning of early and adequate therapeutic interventions.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/psicología , Encefalopatías Metabólicas/complicaciones , Encefalopatías Metabólicas/psicología , Adaptación Psicológica , Errores Innatos del Metabolismo de los Aminoácidos/fisiopatología , Trastornos de la Articulación/etiología , Encefalopatías Metabólicas/fisiopatología , Niño , Conducta Infantil , Preescolar , Cognición , Glutaril-CoA Deshidrogenasa/deficiencia , Humanos , Recién Nacido , Masculino , Destreza Motora , Trastornos de la Destreza Motora/etiología , Tamizaje Neonatal , Pruebas NeuropsicológicasAsunto(s)
Encefalopatías Metabólicas/psicología , Humanidades , Neurología , Relaciones Profesional-Familia , Cuidado Terminal/psicología , Revelación de la Verdad , Adolescente , Encefalopatías Metabólicas/genética , Femenino , Pesar , Humanos , Masculino , Madres/psicología , Rol del Médico/psicologíaAsunto(s)
Encefalopatías Metabólicas/complicaciones , Encefalopatías Metabólicas/patología , Encéfalo/patología , Fibras Nerviosas Mielínicas/patología , Trastornos Neurocognitivos/etiología , Trastornos Neurocognitivos/patología , Adulto , Anisotropía , Encéfalo/fisiopatología , Encefalopatías Metabólicas/psicología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Cuerpo Calloso/patología , Cuerpo Calloso/fisiopatología , Diagnóstico Diferencial , Difusión , Imagen de Difusión por Resonancia Magnética , Progresión de la Enfermedad , Femenino , Pérdida Auditiva Sensorineural/etiología , Humanos , Masculino , Trastornos Neurocognitivos/fisiopatología , Valor Predictivo de las Pruebas , Trastornos Psicóticos/etiología , Trastornos Psicóticos/patología , Trastornos Psicóticos/fisiopatología , Oclusión de la Arteria Retiniana/etiología , Índice de Severidad de la Enfermedad , SíndromeRESUMEN
OBJECTIVE: To describe neuroglycopenia as a specific syndrome caused by insufficient glucose availability during brain development. DESIGN: Neurologic examinations, neuropsychologic tests, biochemical methods, and functional imaging. PARTICIPANTS: Patients afflicted by genetic mutation of the cerebral glucose transporter type 1 and a patient afflicted by persistent infantile hypoglycemia (hyperinsulinism) matched to her healthy twin. RESULTS: The hallmark of the phenotype is the combination of infantile epilepsy and cerebellar and pyramidal tract dysfunction, together with permanent neuropsychologic abnormalities and reduced thalamocortical glucose uptake despite subsequent supply of energetic substrate. CONCLUSIONS: When neuroglycopenia-the lack of adequate glucose supply to the nervous system-occurs in the developing brain, thalamic and cortical metabolism mature aberrantly, causing epilepsy associated with other characteristic neurologic and behavioral disturbances, a pattern also reflected in functional images, as if there were a temporal window during which glucose were crucial for brain development. When maturation is complete, glucose merely serves as a fuel, and then, when deficient, it only causes unrelated disturbances.
Asunto(s)
Encefalopatías Metabólicas/metabolismo , Encéfalo/metabolismo , Glucosa/deficiencia , Adolescente , Adulto , Glucemia/metabolismo , Encéfalo/patología , Encefalopatías Metabólicas/genética , Encefalopatías Metabólicas/psicología , Femenino , Glucosa/líquido cefalorraquídeo , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Hipoglucemia/sangre , Hipoglucemia/patología , Lactante , Masculino , Mutación , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , SíndromeRESUMEN
While accurate and early prediction of patients that will develop Alzheimer's disease (AD) in the near future is urgently needed, the amnestic Mild Cognitive Impairment (MCI) state is of particular interest since it most conveniently represents the pre-dementia stage of AD. Consistently, the profile of brain functional alteration constantly evidenced in resting-state SPECT and PET studies is similar to that observed in mild AD, mainly involving the posterior cingulate and temporo-parietal regions. While the former is a characteristic feature of MCI, since it is present in each patient at this stage, the latter seems specifically associated with the future conversion to AD. Moreover, right temporo-parietal hypometabolism has been found to be the best predictor of subsequent global cognitive decline, over and above neuropsychological and MRI volumetric measurements. This review also presents a discussion on the relationships between the brain profile of hypometabolism on the one hand, and cognitive impairment as well as cerebral structural alterations on the other. Thus, firstly, while functional impairment in the posterior cingulate region seems to be associated with deficits in retrieval of episodic memories in MCI, the relationship between right temporo-parietal hypometabolism and cognitive impairment is still obscure. However, several arguments point to its relation with visuo-spatial deficits, which are often associated with future conversion to AD. Secondly, the discordance between brain areas of major functional changes, and those of highest structural alterations, leads to some relevant questions about the relations between both pathological manifestations and their underlying mechanisms. More specifically, additional hypometabolism-inducing factors could occur in areas of highest hypometabolism compared to atrophy, i.e. mainly in posterior associative cortical regions, leading to genuine functional perturbation in early AD before the development of real atrophy and perhaps of disease as well. By contrast, the hippocampus is the main site of atrophy while its functional alteration is still debated, suggesting that compensation/protective mechanisms probably specifically occur in this structure to maintain a high level of metabolism relative to its structural alteration.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Encefalopatías Metabólicas/metabolismo , Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/metabolismo , Atrofia , Encefalopatías Metabólicas/diagnóstico por imagen , Encefalopatías Metabólicas/psicología , Trastornos del Conocimiento/diagnóstico por imagen , Humanos , Tomografía de Emisión de Positrones , RadiografíaRESUMEN
PURPOSE: To estimate the in vivo intracerebral reducing ability after acute stress in adolescent rats subjected to early neonatal isolation (NI), by performing temporal electron paramagnetic resonance imaging (EPRI) of the brain. MATERIALS AND METHODS: An EPRI system operating at an EPR frequency of 700 MHz was used. The intracerebral reducing ability was estimated based on the halflife of the EPR signal of the blood-brain barrier (BBB)-permeable nitroxide radical. The NI treatment was performed for a period of one hour per day over postnatal days 2-9. Six-week-old rats were exposed to acute stress (immobilization for 90 minutes) prior to the EPRI study. RESULTS: Depletion of the intracerebral reducing ability caused by the acute stress was observed; however, this depletion phenomenon did not occur in animals that were not subjected to NI. CONCLUSION: The results obtained in this study prove that NI induces cerebral vulnerability to acute stress in adolescence.
Asunto(s)
Encefalopatías Metabólicas/etiología , Encéfalo/metabolismo , Aislamiento Social , Estrés Psicológico/complicaciones , Análisis de Varianza , Animales , Animales Recién Nacidos/metabolismo , Barrera Hematoencefálica/metabolismo , Encéfalo/fisiopatología , Encefalopatías Metabólicas/metabolismo , Encefalopatías Metabólicas/psicología , Óxidos N-Cíclicos/metabolismo , Óxidos N-Cíclicos/farmacocinética , Modelos Animales de Enfermedad , Espectroscopía de Resonancia por Spin del Electrón/métodos , Imagenología Tridimensional/métodos , Oxidación-Reducción , Pirrolidinas , Ratas , Ratas Sprague-Dawley , Restricción Física , Estrés Psicológico/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: Magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) are found at higher rates in patients with affective disorders, particularly late-life or treatment-resistant disorders. Studies support a vascular pathogenesis for WMHs in late-life onset disorders; however, pathogenesis in typical early-life onset disorders is less clear. Based on associations between diabetes mellitus and both WMHs and affective disorders, this study investigated the relationship between WMHs and brain glucose metabolism by the polyol pathway-a pathway linked to nervous tissue disease in diabetes. METHODS: Burdens of fluid-attenuated inversion recovery (FLAIR) WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 10 nondiabetic inpatients with treatment-resistant bipolar, unipolar, and schizoaffective disorders and 10 nondiabetic control patients who had been investigated clinically for transient neurological symptoms. RESULTS: Deep but not periventricular WMH burden correlated positively and significantly with elevated CSF concentrations of sorbitol, the specific polyol pathway metabolite of glucose (rho=0.86, p=0.002), in the affective disorders but not the control group. LIMITATIONS: This was a pilot study with a relatively small number of subjects; therefore, conclusions are tentative. Controls were not healthy subjects; they were patients with transient neurological symptoms. CONCLUSIONS: This is the first reported evidence of a relationship between WMHs and increased brain glucose metabolism by the polyol pathway in patients with affective disorders. More extensive studies are necessary to determine whether this preliminary finding represents a pathogenetic relationship.
Asunto(s)
Trastorno Bipolar/tratamiento farmacológico , Glucemia/metabolismo , Encefalopatías Metabólicas/diagnóstico , Encéfalo/patología , Trastorno Depresivo Mayor/tratamiento farmacológico , Diabetes Mellitus Tipo 2/líquido cefalorraquídeo , Glucanos/líquido cefalorraquídeo , Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Trastornos Psicóticos/tratamiento farmacológico , Adulto , Anciano , Trastorno Bipolar/líquido cefalorraquídeo , Trastorno Bipolar/diagnóstico , Encéfalo/metabolismo , Encefalopatías Metabólicas/líquido cefalorraquídeo , Encefalopatías Metabólicas/psicología , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/líquido cefalorraquídeo , Trastorno Depresivo Mayor/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Resistencia a Medicamentos , Femenino , Humanos , Carbonato de Litio/uso terapéutico , Masculino , Persona de Mediana Edad , Proyectos Piloto , Trastornos Psicóticos/líquido cefalorraquídeo , Trastornos Psicóticos/diagnóstico , Psicotrópicos/uso terapéutico , Valores de Referencia , Factores de Riesgo , Sorbitol/líquido cefalorraquídeo , Estadística como Asunto , Clorhidrato de VenlafaxinaAsunto(s)
Encefalopatías Metabólicas/complicaciones , Encefalopatías Metabólicas/tratamiento farmacológico , Complicaciones de la Diabetes , Diabetes Mellitus/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Adulto , Encefalopatías Metabólicas/psicología , Diabetes Mellitus/psicología , Femenino , Humanos , Masculino , Trastornos Mentales/etiología , Resultado del TratamientoRESUMEN
A double mutation in the alpha-secretase site in the betaA4 region of mouse amyloid precursor protein (APP) reduced its secretion from COS cells, polarized MDCK cells and rat primary neurons. Expression of this mutant in the brain of mice, using the neuron-specific elements of the mouse Thy-1 gene promoter, resulted in transgenic mice that became progressively hyperactive, displayed seizures and died prematurely. In three different transgenic lines the severity of the phenotype was related directly to the expression levels of the transgene, estimated by both mRNA and protein levels. In addition, homozygous mice derived from each transgenic strain showed more severe symptoms which also occurred earlier in life than in heterozygotes. The observed symptoms were, however, not essentially different in the different lines. Increased aggressiveness, disturbed responses to kainic acid and N-methyl-D-aspartate, neophobia and deficiency in exploratory behavior were demonstrated in these mice. In the brain, the observed neuropathological changes included necrosis, apoptosis and astrogliosis in the hippocampus, cortex and other areas. The data demonstrate that incomplete or incorrect alpha-secretase processing of APP results in severe neurotoxicity and that this effect is expressed in a dominant manner.