Asunto(s)
Fibrosis Quística/complicaciones , Mielinólisis Pontino Central/complicaciones , Mielinólisis Pontino Central/patología , Enfermedad de Parkinson Secundaria/etiología , Puente/patología , Enfermedad Aguda , Adulto , Antiparkinsonianos/uso terapéutico , Benserazida/uso terapéutico , Combinación de Medicamentos , Humanos , Levodopa/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Enfermedad de Parkinson Secundaria/tratamiento farmacológicoAsunto(s)
Anticonvulsivantes/uso terapéutico , Síndrome de la Persona Rígida/tratamiento farmacológico , Ácido gamma-Aminobutírico/análogos & derivados , Adulto , Carbamazepina/uso terapéutico , Clonazepam/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Retratamiento , Vigabatrin , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
Two patients with meningoradiculitis associated with HIV presented with symptoms and signs of intracranial hypertension. In the patients described, the raised intracranial pressure resolved after lumbar puncture. After exclusion of opportunistic infection, such patients may be managed with therapeutic lumbar puncture alone.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , VIH-1/aislamiento & purificación , VIH-2/aislamiento & purificación , Meningitis Viral/etiología , Seudotumor Cerebral/etiología , Radiculopatía/etiología , Adulto , Femenino , Humanos , Seudotumor Cerebral/terapia , Punción EspinalAsunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Distonía/genética , Glutaratos/orina , Lisina/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Oxidorreductasas/deficiencia , Triptófano/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/orina , Femenino , Glutaril-CoA Deshidrogenasa , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: The EEG correlate of absence seizures is 3-Hz, generalized spike-wave activity. Depth electrode recordings in animal models suggest that spike-wave activity oscillates within thalamocortical circuits, but the site of the primary abnormality is uncertain. The aim of the present study was to determine whether there is a selective increase in blood flow in the thalamus during absence seizures and, if so, whether it precedes the appearance of spike-wave activity on scalp EEG. METHODS: Using PET, regional cerebral blood flow (rCBF) was measured in eight patients with idiopathic generalized epilepsy in whom typical absence seizures were induced by voluntary hyperventilation. Each patient was studied up to 12 times, with an intravenous bolus injection of H2(15)O followed by a 90-second scan. The distribution of rCBF during absence seizures and in the 30 seconds before an absence seizure were compared with the distribution of rCBF when absence seizures did not occur. RESULTS: There was a mean global 14.9% increase in blood flow in association with typical absence seizures and, on top of the global increase, a focal increase in thalamic blood flow of 3.9 to 7.8%. There were no significant focal changes in rCBF in the 30 seconds before the onset of spike-wave activity on the EEG. CONCLUSION: This study provides evidence for the key role of the thalamus in the pathogenesis of absence seizures but was unable to show that it is the site of initiation of the seizures.
Asunto(s)
Epilepsia Tipo Ausencia/diagnóstico por imagen , Epilepsia Tipo Ausencia/fisiopatología , Radioisótopos de Oxígeno , Tálamo/diagnóstico por imagen , Adulto , Circulación Cerebrovascular/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tálamo/irrigación sanguínea , Tomografía Computarizada de Emisión , AguaRESUMEN
The role of benzodiazepine (BZD)-gamma-aminobutyric acidA (GABAA) receptors in the pathogenesis of absence seizures is uncertain. In this study, we examined the effect of absence seizures on the binding of flumazenil to the BZD binding site of the GABAA receptor. Five patients with idiopathic generalized epilepsy (IGE) were studied at rest and during absence seizures with [11C]flumazenil and positron emission tomography (PET). Normalized regional cerebral time-activity curves from the resting and ictal scans were compared with each other and with computed simulations showing the effects of changes in cerebral blood flow (CBF) and [11C]flumazenil binding. No evidence was found for a change in [11C]flumazenil binding with absence seizures. This result, together with those of a recent study showing no abnormality of [11C]flumazenil binding interictally in patients with childhood and juvenile absence epilepsy (JAE) does not support a primary role for the BZD binding site of the GABAA receptor in the pathogenesis of absence seizures.
Asunto(s)
Encéfalo/metabolismo , Epilepsia Tipo Ausencia/metabolismo , Flumazenil/metabolismo , Receptores de GABA-A/metabolismo , Adolescente , Adulto , Edad de Inicio , Encéfalo/diagnóstico por imagen , Radioisótopos de Carbono/metabolismo , Circulación Cerebrovascular , Niño , Epilepsia Tipo Ausencia/diagnóstico por imagen , Epilepsia Generalizada/diagnóstico por imagen , Epilepsia Generalizada/metabolismo , Humanos , Masculino , Tomografía Computarizada de EmisiónRESUMEN
The neurochemical basis of absence seizures and the mechanism of their suppression by valproate (VPA) are uncertain. We used positron emission tomography (PET) to determine whether an abnormality of [11C]flumazenil binding to benzodiazepine (BZD)-GABAA receptors exists in patients with childhood and juvenile absence epilepsy and to examine the effects of VPA on [11C]flumazenil binding. The regional cerebral volume of distribution (Vd) of [11C]flumazenil in patients not treated with VPA was not different from that in normal controls; Vd was lower in patients treated with VPA, and the number of receptors available for binding was significantly reduced in such patients as compared with normal controls. There was no evidence of a primary abnormality of the BZD-GABAA receptor in childhood and juvenile absence epilepsy (CAE/JAE), but the data suggest that treatment with VPA is associated with a reduction in [11C]flumazenil binding that may be relevant to its mode of action in CAE/JAE.
Asunto(s)
Encéfalo/metabolismo , Epilepsia Tipo Ausencia/metabolismo , Flumazenil/metabolismo , Receptores de GABA/metabolismo , Tomografía Computarizada de Emisión , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Radioisótopos de Carbono , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Epilepsia Tipo Ausencia/diagnóstico por imagen , Epilepsia Tipo Ausencia/tratamiento farmacológico , Femenino , Humanos , Masculino , Receptores de GABA/efectos de los fármacos , Ácido Valproico/farmacología , Ácido Valproico/uso terapéuticoRESUMEN
Carbon-11-labeled flumazenil combined with positron emission tomography (PET) was used to measure the concentration (Bmax) of the benzodiazepine (Bz) receptor in the brain and its equilibrium dissociation constant (KD) for flumazenil in five normal subjects. The steady-state approach was used injecting the tracer as a bolus of high specific activity. In each subject two studies were carried out. The first study was performed at essentially zero receptor occupancy, the tracer alone study. The second study was performed at a steady-state receptor occupancy of about 50%, achieved by a prolonged constant infusion of nonlabeled ("cold") flumazenil starting 2h before the bolus tracer injection and continuing until the end of scanning period. In this second study the free concentration of unmetabolized flumazenil in plasma water was measured in multiple blood samples. The observed tissue and plasma tracer curves, calibrated in the same units of radioactivity per millimeter, were analyzed in two ways: (a) by the noncompartmental (stochastic) approach making no assumptions regarding number of compartments in the tissue, and (b) by the single-compartment approach assuming rapid exchange (mixing) of tracer between all tissue compartments. The noncompartmental and the compartmental analyses gave essentially the same values for the distribution volume of the tracer, the parameter used for quantitation of the Bz receptor. As the compartmental approach could be applied to a shorter observation period (60 min instead of 120 min) it was preferred. The five subjects had a mean KD value of 12 nM/L of water and Bmax values of the grey matter ranging from 39 +/- 11 in thalamus to 120 +/- 14 nM/L of brain in occipital cortex. Most previous studies have been based on the pseudoequilibrium approach using the brain stem as a receptor-free reference region. This yields practically the same KD but lower Bmax values than the steady-state approach presented here.
Asunto(s)
Química Encefálica , Radioisótopos de Carbono , Flumazenil , Receptores de GABA-A/análisis , Tomografía Computarizada de Emisión , Adulto , Anciano , Tronco Encefálico/química , Corteza Cerebral/química , Humanos , Cinética , Masculino , Persona de Mediana Edad , Lóbulo Occipital/química , Receptores de GABA-A/metabolismo , Análisis de Regresión , Distribución TisularRESUMEN
The neurochemical basis of absence seizures is uncertain. A previous PET study has provided evidence for release of endogenous opioids from cerebral cortex at the time of absence seizures, but it is has not yet been established whether there is an abnormality of opiate receptor numbers interictally. In the present study, the non-specific opiate receptor ligand, [11C]diprenorphine, was used to measure cerebral opiate receptors interictally in patients with childhood and juvenile absence epilepsy. Eight patients and eight normal controls had a single scan after a high specific activity injection of [11C]diprenorphine. The cerebral volume of distribution (Vd) of [11C]diprenorphine relative to plasma was calculated on a pixel-by-pixel basis. There were no significant differences in [11C]diprenorphine Vd between patients and control subjects in either cortex or thalamus, structures thought to be involved in the pathogenesis of absence seizures. The results suggest that there is no overall abnormality of opioid receptors in patients with childhood and juvenile absence epilepsy. Studies with specific ligands may provide information about the different receptor subtypes.
Asunto(s)
Diprenorfina/metabolismo , Epilepsia Generalizada/metabolismo , Receptores Opioides/metabolismo , Adulto , Epilepsia Generalizada/etiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Ensayo de Unión Radioligante , Tomografía Computarizada de EmisiónRESUMEN
Using PET, reduced glucose metabolism (rCMRglu) and increased binding of the mu opiate receptor ligand 11C-carfentanil have been demonstrated in lateral temporal cortex overlying mesial temporal epileptic foci. Binding of the non-specific opiate receptor ligand 11C-diprenorphine (DPN) to lateral temporal cortex has not shown consistent asymmetries. We measured rCMRglu with 18F-FDG and binding of 11C-diprenorphine in two patients with temporal lobe epilepsy (TLE) before and 5 months after selective amygdalo-hippocampectomy (both patients were seizure-free post-operatively). Pre-operatively, in both patients rCMRglu was decreased in mesial temporal lobe (MTL) (asymmetry index AI = -9.1 and 9.0) ipsilateral to the EEG focus. A more marked reduction was seen in ipsilateral lateral temporal cortex (LTC) (AI = -32.0 and 18.9). DPN binding was reduced in MTL and LTC (AI MTL = -9.3 and 16.2; AI LTC = -8.0 and 5.5) ipsilateral to the focus, but was within 2 SD of the normal range. Post-operatively, the reduction of rCMRglu in LTC was accentuated in one patient and decreased in the other (AI = -23.1 and 45.7) while there was a further reduction of DPN binding in LTC in both patients (AI = -27.8 and 9.8). These preliminary results in only two patients are compatible with downregulation of opiate receptors in LTC after removal of the epileptic focus or post-operative neuronal dysfunction.
Asunto(s)
Amígdala del Cerebelo/cirugía , Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo/cirugía , Receptores Opioides/fisiología , Adulto , Desoxiglucosa/análogos & derivados , Diprenorfina , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Radioisótopos de Flúor , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Tomografía Computarizada de EmisiónRESUMEN
The neuroanatomical and pathophysiological basis of primary generalised absences is uncertain. Administration of endogenous opioids has been shown to result in absence-like seizures in animal models. Positron emission tomography scans were performed in eight patients with primary generalised epilepsy and eight control subjects. Regional cerebral blood flow was measured interictally with C15O2, after which a 90 minute dynamic study with the opioid-receptor ligand 11C-diprenorphine was performed. Serial absences were precipitated by hyperventilation for 10 minutes, starting 30-40 minutes after injection of diprenorphine. Absences, with generalised spike-wave discharges on the EEG, occurred for between 10% and 51% of the provocation period. No individual (normal or patient) had any interictal focal abnormalities of cerebral blood flow. After provocation of serial absence seizures, there was increased diprenorphine elimination from the association cortex, but not from the thalamus, basal ganglia, or cerebellum, compared with control subjects and patients scanned without provocation of absences. It was possible to simulate the observed increased diprenorphine elimination following seizures in cerebral cortex using a two tissue compartment model, with an estimated 15-41% decrease in the specific tracer uptake rate constant (k3). These results suggest that endogenous opioids are released in the association cortex at the time of serial absences, lead to increased receptor occupancy, and may have an important role in the pathophysiology of generalised absences.