RESUMEN
BACKGROUND: Impaired cortical inhibiton and maladaptive cortical plasticity are functional hallmarks of sporadic focal dystonias. Whether or not these mechanisms translate to generalized dystonias and whether these features reflect state or trait characteristics are topics of research in hereditary dystonias. METHODS: We present a series of studies using a multitracer approach with positron emission tomography (PET) and diffusion tensor MRI (DTI) in the DYT1 and the DYT6 genotype. RESULTS: In these hereditary dystonias functional and microstructural abnormalities were found in cortico-striatal-pallido-thalamocortical (CSPTC) and cerebellar-thalamo-cortical circuits. Genotype-specific abnormalities were localized to the basal ganglia, SMA and cerebellum. Functional changes, as potential correlates of maladaptive sensorimotor plasticity were found throughout the sensorimotor system and were more pronounced in affected mutation carriers than in their non-manifesting counterparts. In both genotypes, striatal metabolic abnormalities were paralleled by genotype-specific reductions in D(2) receptor availability. However, these reductions failed to show a clear association with clinical or functional markers of the disease. By contrast, microstructural changes of cerebellar pathways clearly related to penetrance and may thus represent the main intrinsic abnormality underlying cortical downstream effects, such as increased sensorimotor responsivity. CONCLUSIONS: These studies are consistent with the view of primary torsion dystonia as a neurodevelopmental circuit disorder involving CSPTC and related cerebellar pathways.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen de Difusión Tensora/métodos , Trastornos Distónicos , Tomografía de Emisión de Positrones/métodos , Mapeo Encefálico , Trastornos Distónicos/diagnóstico por imagen , Trastornos Distónicos/genética , Trastornos Distónicos/fisiopatología , Humanos , Discapacidades para el Aprendizaje/etiología , Discapacidades para el Aprendizaje/genética , Chaperonas Moleculares/genética , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Receptores de Dopamina D2/genéticaRESUMEN
The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD) is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve p-HD subjects were followed longitudinally with [11C]-raclopride and [18F]-fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive declines in striatal D2-receptor binding were correlated with concurrent changes in regional metabolism and in the activity of an HD-related metabolic network. We found that striatal D2 binding declined over time (P < 0.005). The activity of a reproducible HD-related metabolic covariance pattern increased between baseline and 18 months (P < 0.003) but declined at 44 months (P < 0.04). These network changes coincided with progressive declines in striatal and thalamic metabolic activity (P < 0.01). Striatal metabolism was abnormally low at all time points (P < 0.005). By contrast, thalamic metabolism was elevated at baseline (P < 0.01), but fell to subnormal levels in the p-HD subjects who developed symptoms. These findings were confirmed with an MRI-based atrophy correction for each individual PET scan. Increases in network expression and thalamic glucose metabolism may be compensatory for early neuronal losses in p-HD. Declines in these measures may herald the onset of symptoms in gene carriers.
Asunto(s)
Enfermedad de Huntington/diagnóstico por imagen , Enfermedad de Huntington/metabolismo , Tálamo/metabolismo , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Progresión de la Enfermedad , Fluorodesoxiglucosa F18/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/metabolismo , Heterocigoto , Humanos , Enfermedad de Huntington/genética , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Corteza Motora/diagnóstico por imagen , Corteza Motora/metabolismo , Pruebas Neuropsicológicas , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Occipital/metabolismo , Tomografía de Emisión de Positrones , Unión Proteica , Racloprida/metabolismo , Radiofármacos/metabolismo , Receptores de Dopamina D2/metabolismo , Tálamo/diagnóstico por imagenRESUMEN
Learning deficits may be part of the early symptoms of Huntington's disease (HD). Here we characterized implicit and explicit aspects of sequence learning in 11 pre-symptomatic HD gene carriers (pHD) and 11 normal controls. Subjects moved a cursor on a digitizing tablet and performed the following tasks: SEQ: learning to anticipate the appearance of a target sequence in two blocks; VSEQ: learning a sequence by attending to the display without moving for one block, and by moving to the sequence in a successive block (VSEQ test). Explicit learning was measured with declarative scores and number of anticipatory movements. Implicit learning was measured as a strategy change reflected in movement time. By the end of SEQ, pHD had a significantly lower number of correct anticipatory movements and lower declarative scores than controls, while in VSEQ and VSEQ test these indices improved. During all three tasks, movement time changed in controls, but not in pHD. These results suggest that both explicit and implicit aspects of sequence learning may be impaired before the onset of motor symptoms. However, when attentional demands decrease, explicit, but not implicit, learning may improve.
Asunto(s)
Enfermedad de Huntington/psicología , Aprendizaje Seriado/fisiología , Adulto , Cognición/fisiología , Interpretación Estadística de Datos , Femenino , Humanos , Masculino , Memoria/fisiología , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología , Percepción Espacial/fisiología , Aprendizaje Verbal/fisiologíaRESUMEN
There is a compelling need for early, accurate diagnosis of Parkinson's disease (PD). Various magnetic resonance imaging modalities are being explored as an adjunct to diagnosis. A significant challenge in using MR imaging for diagnosis is developing appropriate algorithms for extracting diagnostically relevant information from brain images. In previous work, we have demonstrated that individual subject variability can have a substantial effect on identifying and determining the borders of regions of analysis, and that this variability may impact on prediction accuracy. In this paper we evaluate a new statistical algorithm to determine if we can improve accuracy of prediction using a subjects left-out validation of a DTI analysis. Twenty subjects with PD and 22 healthy controls were imaged to evaluate if a full brain diffusion tensor imaging-fractional anisotropy (DTI-FA) map might be capable of segregating PD from controls. In this paper, we present a new statistical algorithm based on bootstrapping. We compare the capacity of this algorithm to classify the identity of subjects left out of the analysis with the accuracy of other statistical techniques, including standard cluster-thresholding. The bootstrapped analysis approach was able to correctly discriminate the 20 subjects with PD from the 22 healthy controls (area under the receiver operator curve or AUROC 0.90); however the sensitivity and specificity of standard cluster-thresholding techniques at various voxel-specific thresholds were less effective (AUROC 0.72-0.75). Based on these results sufficient information to generate diagnostically relevant statistical maps may already be collected by current MRI scanners. We present one statistical technique that might be used to extract diagnostically relevant information from a full brain analysis.
Asunto(s)
Algoritmos , Encéfalo/patología , Imagen de Difusión Tensora , Interpretación de Imagen Asistida por Computador/métodos , Enfermedad de Parkinson/diagnóstico , Anciano , Área Bajo la Curva , Mapeo Encefálico/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y EspecificidadRESUMEN
This gene transfer experiment is the first Parkinson's Disease (PD) protocol to be submitted to the Recombinant DNA Advisory Committee. The principal investigators have uniquely focused their careers on both pre-clinical work on gene transfer in the brain and clinical expertise in management and surgical treatment of patients with PD. They have extensively used rodent models of PD for proof-of-principle experiments on the utility of different vector systems. PD is an excellent target for gene therapy, because it is a complex acquired disease of unknown etiology (apart from some rare familial cases) yet it is characterized by a specific neuroanatomical pathology, the degeneration of dopamine neurons of the substantia nigra (SN) with loss of dopamine input to the striatum. This pathology results in focal changes in the function of several deep brain nuclei, which have been well-characterized in humans and animal models and which account for many of the motor symptoms of PD. Our original approaches, largely to validate in vivo gene transfer in the brain, were designed to facilitate dopamine transmission in the striatum using an AAV vector expressing dopamine-synthetic enzymes. Although these confirmed the safety and potential efficacy of AAV, complex patient responses to dopamine augmenting medication as well as poor results and complications of human transplant studies suggested that this would be a difficult and potentially dangerous clinical strategy using current approaches. Subsequently, we and others investigated the use of growth factors, including GDNF. These showed some encouraging effects on dopamine neuron survival and regeneration in both rodent and primate models; however, uncertain consequences of long-term growth factor expression and question regarding timing of therapy in the disease course must be resolved before any clinical study can be contemplated. We now propose to infuse into the subthalamic nucleus (STN) recombinant AAV vectors expressing the two isoforms of the enzyme glutamic acid decarboxylase (GAD-65 and GAD-67), which synthesizes the major inhibitory neurotransmitter in the brain, GABA. The STN is a very small nucleus (140 cubic mm or 0.02% of the total brain volume, consisting of approximately 300,000 neurons) which is disinhibited in PD, leading to pathological excitation of its targets, the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNpr). Increased GPi/SNpr outflow is believed responsible for many of the cardinal symptoms of PD, i.e., tremor, rigidity, bradykinesia, and gait disturbance. A large amount of data based on lesioning, electrical stimulation, and local drug infusion studies with GABA-agonists in human PD patients have reinforced this circuit model of PD and the central role of the STN. Moreover, the closest conventional surgical intervention to our proposal, deep brain stimulation (DBS) of the STN, has shown remarkable efficacy in even late stage PD, unlike the early failures associated with recombinant GDNF infusion or cell transplantation approaches in PD. We believe that our gene transfer strategy will not only palliate symptoms by inhibiting STN activity, as with DBS, but we also have evidence that the vector converts excitatory STN projections to inhibitory projections. This additional dampening of outflow GPi/SNpr outflow may provide an additional advantage over DBS. Moreover, of perhaps the greatest interest, our preclinical data suggests that this strategy may also be neuroprotective, so this therapy may slow the degeneration of dopaminergic neurons. We will use both GAD isoforms since both are typically expressed in inhibitory neurons in the brain, and our data suggest that the combination of both isoforms is likely to be most beneficial. Our preclinical data includes three model systems: (1) old, chronically lesioned parkinsonian rats in which intraSTN GAD gene transfer results not only in improvement in both drug-induced asymmetrical behavior (apomorphine symmetrical rotations), but also in spontaneous behaviors. In our second model, GAD gene transfer precedes the generation of a dopamine lesion. Here GAD gene transfer showed remarkable neuroprotection. Finally, we carried out a study where GAD-65 and GAD-67 were used separately in monkeys that were resistant to MPTP lesioning and hence showed minimal symptomatology. Nevertheless GAD gene transfer showed no adverse effects and small improvements in both Parkinson rating scales and activity measures were obtained. In the proposed clinical trial, all patients will have met criteria for and will have given consent for STN DBS elective surgery. Twenty patients will all receive DBS electrodes, but in addition they will be randomized into two groups, to receive either a solution containing rAAV-GAD, or a solution which consists just of the vector vehicle, physiological saline. Patients, care providers, and physicians will be blind as to which solution any one patient receives. All patients, regardless of group, will agree to not have the DBS activated until the completion and unblinding of the study. Patients will be assessed with a core clinical assessment program modeled on the CAPSIT, and in addition will also undergo a preop and several postop PET scans. At the conclusion of the study, if any patient with sufficient symptomatic improvement will be offered DBS removal if they so desire. Any patients with no benefit will simply have their stimulators activated, which would normally be appropriate therapy for them and which requires no additional operations. If any unforeseen symptoms occur from STN production of GABA, this might be controlled by blocking STN GABA release with DBS, or STN lesioning could be performed using the DBS electrode. Again, this treatment would not subject the patient to additional invasive brain surgery. The trial described here reflects an evolution in our thinking about the best strategy to make a positive impact in Parkinson Disease by minimizing risk and maximizing potential benefit. To our knowledge, this proposal represents the first truly blinded, completely controlled gene or cell therapy study in the brain, which still provides the patient with the same surgical procedure which they would normally receive and should not subject the patient to additional surgical procedures regardless of the success or failure of the study. This study first and foremost aims to maximally serve the safety interests of the individual patient while simultaneously serving the public interest in rigorously determining in a scientific fashion if gene therapy can be effective to any degree in treating Parkinson's disease.
Asunto(s)
Protocolos Clínicos , Terapia por Estimulación Eléctrica/métodos , Técnicas de Transferencia de Gen , Terapia Genética/legislación & jurisprudencia , Terapia Genética/métodos , Glutamato Descarboxilasa/genética , Enfermedad de Parkinson/terapia , Núcleo Celular/metabolismo , Terapia Combinada , Dependovirus/genética , Vectores Genéticos , Glutamato Descarboxilasa/química , Humanos , Isoformas de ProteínasRESUMEN
BACKGROUND: Executive control of cognition, emotion, and behavior are disrupted in the manic state of bipolar disorder. Whereas frontal systems are implicated in such dysfunction, the localization of functional brain abnormalities in the manic state is not well understood. METHODS: We utilized a high-sensitivity H(2)(15)0 positron emission tomography technique to investigate regions of increased brain activity in mania, compared to euthymia, in bipolar disorder. RESULTS: The principal findings were manic state-related increased activity in left dorsal anterior cingulate, and left head of caudate. CONCLUSIONS: The findings suggest that the manic state of bipolar disorder may be associated with heightened activity in a frontal cortical-subcortical neural system that includes the anterior cingulate and caudate.
Asunto(s)
Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/fisiopatología , Núcleo Caudado/fisiopatología , Circulación Cerebrovascular , Dominancia Cerebral , Giro del Cíngulo/fisiopatología , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Estudios de Casos y Controles , Núcleo Caudado/irrigación sanguínea , Núcleo Caudado/diagnóstico por imagen , Cognición , Factores de Confusión Epidemiológicos , Femenino , Giro del Cíngulo/irrigación sanguínea , Giro del Cíngulo/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Tomografía Computarizada de EmisiónRESUMEN
Fluorine (19F) nuclear magnetic resonance may be used to image cerebral perfusion in cats receiving perfluorocarbon blood substitutes. 19F relaxation times in these blood substitutes are dependent on oxygen tension (PO2) and may be used to calculate and spatially map cerebrovascular PO2 values in vivo. We have applied this noninvasive method to experimental middle cerebral artery (MCA) occlusion. Following MCA occlusion a perfusion defect is evident in the sylvian region, followed by the appearance of collaterals. Signal from the ipsilateral rete mirabilis is increased. Calculated cortical vascular PO2 values indicate a relative reduction in oxygenation in the ischaemic hemisphere. PO2 maps show a perfused hypoxaemic zone adjacent to the perfusion defect. These changes are partly reversed with reperfusion.
Asunto(s)
Química Encefálica , Espectroscopía de Resonancia Magnética , Oxígeno/análisis , Animales , Gatos , Arterias Cerebrales , Constricción , FlúorRESUMEN
L-[18F]6-Fluoro-DOPA (L-[18F]6-fluoro-3,4-dihydroxyphenylalanine; FDOPA) has been used with quantitative positron emission tomography (PET) to assess presynaptic nigrostriatal dopaminergic function in life. The relationship of estimated kinetic rate constants for striatal FDOPA uptake [Ki(FDOPA)] to the normal aging process has been the subject of conflicting reports. Resolution of this issue has been hampered by methodological differences in previous FDOPA/PET investigations. We studied 19 healthy normal subjects (aged 27-77 years) and measured striatal Ki-(FDOPA) according to each of the earlier methods. While significant correlations (p < 0.005) existed between Ki(FDOPA) values estimated by the various techniques, none correlated with normal aging. We conclude that normal striatal Ki(FDOPA) values estimated using quantitative FDOPA/PET are uncorrelated with the aging process.
Asunto(s)
Envejecimiento/metabolismo , Cuerpo Estriado/metabolismo , Dihidroxifenilalanina/análogos & derivados , Adulto , Anciano , Cuerpo Estriado/diagnóstico por imagen , Dihidroxifenilalanina/sangre , Dihidroxifenilalanina/farmacocinética , Dihidroxifenilalanina/farmacología , Femenino , Radioisótopos de Flúor , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Tomografía Computarizada de EmisiónRESUMEN
We used [18F]fluorodeoxyglucose/positron emission tomography (18F-FDG/PET) and a statistical model of regional covariation to study brain topographic organization in parkinsonism. We studied 22 patients with Parkinson's disease (PD), 20 age-matched normal volunteers, and 10 age- and severity-matched patients with presumed striatonigral degeneration (SND). We used FDG/PET to calculate global, regional, and normalized metabolic rates for glucose (GMR, rCMRglc, rCMRglc/GMR). Metabolic parameters in the three groups were compared using an analysis of variance, with a correction for multiple comparisons, and discriminant analysis. The scaled subprofile model (SSM) was applied to the combined rCMRglc dataset to identify topographic covariance profiles that distinguish PD patients from SND patients and normals. GMR, rCMRglc, and rCMRglc/GMR were normal in PD; caudate and lentiform rCMRglc/GMR was reduced in the SND group (p < 0.01). SSM analysis of the combined group of patients and normals revealed a significant topographic profile characterized by increased metabolic activity in the lentiform nucleus and thalamus associated with decreased activity in the lateral frontal, paracentral, inferior parietal, and parietooccipital areas. Individual subject scores for this profile were significantly elevated in PD patients compared with normals and SND patients (p < 0.001) and discriminated the three groups. In the PD group, subject scores for this factor correlated with individual subject Hoehn and Yahr (H & Y) scores (p < 0.02), and with quantitative rigidity (p < 0.01) and bradykinesia (p < 0.03) ratings, but not with tremor ratings. SSM analysis of right-left metabolic asymmetries yielded a topographic contrast profile that accurately discriminated mildly affected PD patients (H & Y Stage I) from normals. Our findings demonstrate that abnormal topographic covariance profiles exist in parkinsonism. These profiles have potential clinical application as neuroimaging markers in parkinsonism.
Asunto(s)
Encéfalo/fisiopatología , Enfermedad de Parkinson/diagnóstico por imagen , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encefalopatías/fisiopatología , Mapeo Encefálico , Cuerpo Estriado/fisiopatología , Femenino , Glucosa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Sustancia Negra/fisiopatología , Tomografía Computarizada de EmisiónRESUMEN
Flurodopa (FDOPA) is an analogue of L-di-hydroxyphenylalanine (L-dopa) used to assess the nigrostriatal dopamine system in vivo with positron emission tomography (PET). However, FDOPA/PET quantitation is complicated by the presence of the 3-O-methyl-FDOPA (3OMFD) fraction in brain and plasma. Pretreatment with entacapone (OR-611), a peripheral catechol O-methyl-transferase (COMT) inhibitor, greatly reduces the plasma 3OMFD fraction and provides an ideal situation to evaluate the contribution of the plasma 3OMFD fraction in several kinetic models of FDOPA uptake. We performed FDOPA/PET with and without the OR-611 preadministration in six Parkinson's disease (PD) patients. We measured the time-course of the plasma FDOPA and 3OMFD fractions using high-pressure liquid chromatography (HPLC). We calculated striato-occipital ratios (SOR), and estimated the striatal FDOPA uptake rate constant graphically using the plasma FDOPA and occipital tissue time activity curves (KiFD and KiOCC, respectively). We also estimated striatal dopa decarboxylase (DDC) activity (k3D) using a model incorporating independent measurements of 3OMFD transport kinetic rate constants. With the preadministration of OR-611, the pharmacological efficiency in plasma was prolonged significantly (21.1-37.7%; p < 0.01). We also observed significant mean elevations in SOR and KiOCC by 21.8 and 53.5%, respectively (p < 0.05). KiFD and k3D did not show significant change. We conclude that OR-611 prolongs the circulation time of FDOPA in the plasma but does not alter rate constants for striatal FDOPA uptake or decarboxylation.
Asunto(s)
Inhibidores de Catecol O-Metiltransferasa , Dihidroxifenilalanina/análogos & derivados , Enfermedad de Parkinson/sangre , Tomografía Computarizada de Emisión/métodos , Tirosina/análogos & derivados , Adulto , Anciano , Catecoles/farmacología , Cromatografía Líquida de Alta Presión , Cuerpo Estriado/metabolismo , Dihidroxifenilalanina/sangre , Inhibidores Enzimáticos/farmacología , Femenino , Radioisótopos de Flúor , Humanos , Cinética , Masculino , Persona de Mediana Edad , Nitrilos , Lóbulo Occipital/metabolismo , Control de Calidad , Sensibilidad y Especificidad , Tomografía Computarizada de Emisión/estadística & datos numéricos , Tirosina/sangreRESUMEN
Normal aging is associated with the degeneration of specific neural systems. We used [18F] fluorodeoxyglucose (FDG)/positron emission tomography (PET) and a statistical model of regional covariation to explore the metabolic topography of this process. We calculated global and regional metabolic rates for glucose (GMR and rCMRglc) in two groups of normal subjects studied independently on different tomographs: Group 1--130 normal subjects (62 men and 68 women; range 21-90 years); Group 2--20 normal subjects (10 men and 10 women; range 24-78 years). In each of the two groups, the Scaled Subprofile Model (SSM) was applied to rCMRglc data to identify specific age-related profiles. The validity of these profiles as aging markers was assessed by correlating the associated subject scores with chronological age in both normal populations. SSM analysis disclosed two significant topographic profiles associated with aging. The first topographic profile, extracted in an analysis of group 1 normals, was characterized by relative frontal hypometabolism associated with covariate metabolic increases in the parietooccipital association areas, basal ganglia, mid-brain, and cerebellum. Subject scores for this profile correlated significantly with age in both normal groups (R2 = 0.48 and 0.33, p < 0.0001 for groups 1 and 2, respectively). Because of clinical similarities between normal motoric aging and parkinsonism, we explored the possibility of shared elements in the metabolic topography of both processes. We performed a combined group SSM analysis of the 20 group 2 normals and 22 age-matched Parkinson's disease patients, and identified another aging-related topographic profile. This profile was characterized by relative basal ganglia hypermetabolism associated with covariate decreases in frontal premotor cortex. Subject scores for this profile also correlated significantly with age in both normal groups (group 1: R2 = 0.30, p < 0.00001; group 2: R2 = 0.59, p < 0.01). Healthy aging is associated with reproducible topographic covariation profiles associated with specific neural systems. FDG/PET may provide a useful metabolic marker of the normal aging process.
Asunto(s)
Envejecimiento/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Tomografía Computarizada de Emisión , Adulto , Anciano , Anciano de 80 o más Años , Mapeo Encefálico , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Femenino , Radioisótopos de Flúor , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Enfermedad de Parkinson/metabolismo , Valores de Referencia , Análisis de Regresión , Tomografía Computarizada de Emisión/métodosRESUMEN
OBJECTIVE: The authors assessed frontotemporal function in patients with geriatric depression, a debilitating and increasingly prevalent disorder that has not been examined with brain activation paradigms. METHOD: Six depressed elderly patients and five healthy comparison subjects underwent high-sensitivity [(15)O]H(2)O positron emission tomography scans during a paced word generation task and a resting condition. RESULTS: Bilateral activation deficits were noted in the dorsal anterior cingulate gyrus and hippocampus of the depressed geriatric patients relative to the comparison subjects. Patients had memory deficits that correlated with lower hippocampal activity during both rest and activation. CONCLUSIONS: These initial findings suggest that hippocampal and dorsal anterior cingulate hypoactivation may constitute contributing neural substrates of geriatric depression. They also suggest that hippocampal dysfunction is related to the memory dysfunction characteristic of this disorder.
Asunto(s)
Trastorno Depresivo/fisiopatología , Giro del Cíngulo/fisiopatología , Hipocampo/fisiopatología , Factores de Edad , Anciano , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/diagnóstico por imagen , Femenino , Evaluación Geriátrica , Giro del Cíngulo/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Humanos , Masculino , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/fisiopatología , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Radioisótopos de Oxígeno , Tomografía Computarizada de Emisión/estadística & datos numéricosRESUMEN
OBJECTIVE: This study was undertaken to clarify earlier inconsistent findings in brain metabolic topography in panic disorder patients at rest. METHOD: Positron emission tomography (PET) with [18F]fluorodeoxyglucose was used to determine cerebral metabolic activity in six female patients with a DSM-III-R diagnosis of panic disorder and in six healthy female volunteers. All patients with panic disorder were medication free and were sensitive to lactate infusion. RESULTS: A significant increase in glucose metabolism was found in the left hippocampus and parahippocampal area of the panic disorder subjects in comparison with that found in the healthy subjects. In addition, a significant decrease in metabolism was found in the right inferior parietal and right superior temporal brain regions of the panic disorder subjects in comparison with that of the normal subjects. There was no significant correlation between scores for the severity of panic disorder or for the severity of lactate-induced panic attack and the quantified PET abnormality. CONCLUSIONS: These data provide further support for the hypothesis of an abnormal brain metabolism in the hippocampal and parahippocampal area in individuals with panic disorder and also suggest other areas of aberrant brain metabolism in this disorder.
Asunto(s)
Glucosa/metabolismo , Trastorno de Pánico/diagnóstico por imagen , Trastorno de Pánico/metabolismo , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Hipocampo/diagnóstico por imagen , Hipocampo/metabolismo , Humanos , Persona de Mediana Edad , Tomografía Computarizada de EmisiónRESUMEN
OBJECTIVE: This study investigated prefrontal cortex function in the manic state of bipolar disorder. METHOD: High-sensitivity [15O]H2O positron emission tomography and a word generation activation paradigm were used to study regional cerebral blood flow in five manic and six euthymic individuals with bipolar disorder and in five healthy individuals. RESULTS: Decreased right rostral and orbital prefrontal cortex activation during word generation and decreased orbitofrontal activity during rest were associated with mania. CONCLUSIONS: The data support the presence of rostral and orbital prefrontal dysfunction in primary mania. These findings, when seen in the context of the human brain lesion and the behavioral neuroanatomic literatures, may help to explain some of the neurobehavioral abnormalities characteristic of the manic state.
Asunto(s)
Trastorno Bipolar/fisiopatología , Pruebas Neuropsicológicas , Corteza Prefrontal/fisiopatología , Tomografía Computarizada de Emisión , Adulto , Trastorno Bipolar/diagnóstico por imagen , Femenino , Humanos , Masculino , Radioisótopos de Oxígeno , Corteza Prefrontal/irrigación sanguínea , Corteza Prefrontal/diagnóstico por imagen , Flujo Sanguíneo Regional , AguaRESUMEN
We parceled the posterior thalami of nine normal human brains according to cytoarchitectonic criteria, measured relevant nuclear volumes, and sought left-right asymmetries. We found that thalamic zones with multiple projections to the cerebral cortex, using the centromedian-parafascicular nucleus as a prototype, were mostly symmetric. This group includes the medial, lateral, and inferior pulvinar nuclei. Thalamic zones that project discretely to a few, clearly defined cortical receptor fields (using the medial geniculate nucleus [MG] as a prototype) closely reflected the asymmetry of the cortical fields to which they project. Hence, the MG showed a slight right-sided bias, and the lateralis posterior nucleus (related to the grossly asymmetric inferior parietal lobule) showed a significant leftsided bias in eight of the nine brains measured. This asymmetry may partially explain the apparent language specialization of the dominant thalamus.
Asunto(s)
Tálamo/anatomía & histología , Adolescente , Adulto , Anciano , Corteza Cerebral/anatomía & histología , Niño , Preescolar , Dominancia Cerebral , Femenino , Humanos , Lactante , Lenguaje/fisiología , Masculino , Persona de Mediana Edad , Vías Nerviosas/anatomía & histología , Técnicas Estereotáxicas , Núcleos Talámicos/anatomía & histología , Tálamo/fisiologíaRESUMEN
Architectonic parcellation of the parietal lobes of eight human brains, with special attention paid to the inferior parietal lobule, resulted in a map that bore a close relationship to previous maps and took into consideration modern data on physiology and connections. Two general parietal zones were distinguished, one above and the other below the intraparietal sulcus, similar to the dorsal-ventral distinction suggested for the frontal lobe. Five areas were recognized in the inferior parietal lobule, of which areas parietal areas EG (PEG), G (PG), and occipitoparietal G (OPG) were in the angular gyrus. A lateralization toward the right was found for area PEG, an area structurally similar to the visually related cortices of the posterior superior parietal region. A lateralization toward the left was found for area PG, but only in brains with a larger left planum temporale. The asymmetry in area PG seemed to be linked to other asymmetries present in language areas, whereas the right-sided area PEG preponderance showed no relation to the language asymmetries.
Asunto(s)
Lóbulo Parietal/anatomía & histología , Adulto , Anciano , Mapeo Encefálico , Niño , Preescolar , Femenino , Humanos , Lenguaje , Masculino , Persona de Mediana EdadRESUMEN
The cytoarchitecture of the brain of a patient with developmental dyslexia was analyzed. The cortical abnormalities, consisting of micropolygyria encompassing most of posterior temporoparietal area and ectopic cell collections elsewhere have been described previously. In this study, the posterior thalamus was likewise analyzed, and a bilateral disruption of cytoarchitecture was noted in the medial geniculate nucleus and the lateralis posterior nucleus, a nuclear group of probable relevance to language found to be asymmetric.
Asunto(s)
Dislexia/patología , Enfermedades Talámicas/patología , Corteza Cerebral/patología , Preescolar , Dominancia Cerebral , Humanos , Masculino , Vías Nerviosas/patología , Tálamo/fisiopatologíaRESUMEN
In an effort to improve the clinical signs of Parkinson's disease, we have implanted mesencephalic dopamine cells from a 7-week human embryo into the caudate and putamen of a 52-year-old man with Parkinson's disease. Fetal tissue was obtained from elective abortion. The woman and the patient with Parkinson's disease were unknown to each other. The woman gave specific consent and was not paid. The patient had a 20-year history of parkinsonism treated with multiple drug therapies including levodopa/carbidopa (Sinemet) every 2 1/2 hours. His symptoms were worse on the left side. For 5 months prior to transplantation, the patient underwent clinical evaluations by both a neurologist and a computer system installed in his home for daily measurement of walking and hand movements. Preoperative positron emission tomographic scanning with 6-L[18F]fluorodopa (fluorodopa) demonstrated severe dopamine depletion bilaterally. Fetal tissue was matched to the patient for ABO blood antigens, and maternal serum was screened for hepatitis B and human immunodeficiency virus type 1 prior to surgery. Fetal tissue was implanted stereotactically throughout the caudate and putamen on the right side of the brain via 10 needle tracks. The patient was not immunosuppressed. Results 12 months after surgery showed 42% improvement in left-hand speed before the first morning dose of drug and 40% greater response to drug therapy. Right-hand speed increased 15% before drug therapy and 23% after drug therapy. Reaction time was unaffected. Walking speed increased 33% after drug administration, although walking speed before the first morning dose of drugs declined 40%. Walking speed on an all-day basis improved 17%.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Dopamina/metabolismo , Mesencéfalo/trasplante , Enfermedad de Parkinson/terapia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Feto , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Mesencéfalo/embriología , Mesencéfalo/metabolismo , Persona de Mediana Edad , Movimiento , Examen Neurológico , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Tomografía Computarizada de Emisión , Tomografía Computarizada por Rayos XRESUMEN
We used 18F-fluorodeoxyglucose and PET to study a 23-year-old woman with alternating hemichorea and primary antiphospholipid syndrome. There were three PET studies: (1) during an episode of right hemichorea, (2) during an asymptomatic period 6 months later, and (3) during an episode of left hemichorea occurring 2 months after that. In each study, we calculated normalized regional glucose metabolism for the caudate and lentiform nuclei and compared these values with those calculated in 12 normal volunteer subjects (mean age, 35.3 +/- 9.0). The following results were obtained: (1) during right hemichorea, left lentiform metabolism was increased by 19% (> 3 SD); (2) during the asymptomatic period, right caudate metabolism was increased by 20% (> 3 SD), and right lentiform and left striatal metabolism were normal; and (3) during left hemichorea, right caudate and lentiform metabolism were both elevated by 33% (> 3 SD). During this episode, left caudate metabolism was elevated by 20% (> 2 SD); left lentiform metabolism was normal. These results suggest that hemichorea in primary antiphospholipid syndrome may be associated with contralateral striatal hypermetabolism that may also be present during asymptomatic periods.
Asunto(s)
Síndrome Antifosfolípido/metabolismo , Corea/metabolismo , Cuerpo Estriado/metabolismo , Adulto , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico por imagen , Corea/complicaciones , Corea/diagnóstico por imagen , Cuerpo Estriado/diagnóstico por imagen , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Humanos , Tomografía Computarizada de EmisiónRESUMEN
Eleven patients suffering from Parkinson's disease were followed for up to 4 years after unilateral pallidotomy. We observed persistent contralateral improvement and unexpected ipsilateral improvement of motor symptoms. In addition, there was a protracted relief of contralateral dyskinesias and maintenance of relatively stable levodopa dosage.