RESUMEN
Disentangling Parkinson's disease (PD) and progressive supranuclear palsy (PSP) may be a diagnostic challenge. Cognitive signs may be useful, but existing screens are often insufficiently sensitive or unsuitable for assessing people with motor disorders. We investigated whether the newly developed ECAS, designed to be used with people with even severe motor disability, was sensitive to the cognitive impairment seen in PD and PSP and able to distinguish between these two disorders. Thirty patients with PD, 11 patients with PSP, and 40 healthy controls were assessed using the ECAS, as well as an extensive neuropsychological assessment. The ECAS detected cognitive impairment in 30% of the PD patients, all of whom fulfilled the diagnostic criteria for mild cognitive impairment. The ECAS was also able to detect cognitive impairment in PSP patients, with 81.8% of patients performing in the impaired range. The ECAS total score distinguished between the patients with PSP and healthy controls with high sensitivity (91.0) and specificity (86.8). Importantly, the ECAS was also able to distinguish between the two syndromes, with the measures of verbal fluency offering high sensitivity (82.0) and specificity (80.0). In sum, the ECAS is a quick, simple, and inexpensive test that can be used to support the differential diagnosis of PSP.
RESUMEN
Speed-accuracy trade-off is an intensively studied law governing almost all behavioral tasks across species. Here we show that motivation by reward breaks this law, by simultaneously invigorating movement and improving response precision. We devised a model to explain this paradoxical effect of reward by considering a new factor: the cost of control. Exerting control to improve response precision might itself come at a cost--a cost to attenuate a proportion of intrinsic neural noise. Applying a noise-reduction cost to optimal motor control predicted that reward can increase both velocity and accuracy. Similarly, application to decision-making predicted that reward reduces reaction times and errors in cognitive control. We used a novel saccadic distraction task to quantify the speed and accuracy of both movements and decisions under varying reward. Both faster speeds and smaller errors were observed with higher incentives, with the results best fitted by a model including a precision cost. Recent theories consider dopamine to be a key neuromodulator in mediating motivational effects of reward. We therefore examined how Parkinson's disease (PD), a condition associated with dopamine depletion, alters the effects of reward. Individuals with PD showed reduced reward sensitivity in their speed and accuracy, consistent in our model with higher noise-control costs. Including a cost of control over noise explains how reward may allow apparent performance limits to be surpassed. On this view, the pattern of reduced reward sensitivity in PD patients can specifically be accounted for by a higher cost for controlling noise.
Asunto(s)
Cognición/fisiología , Toma de Decisiones/fisiología , Modelos Neurológicos , Actividad Motora/fisiología , Enfermedad de Parkinson/fisiopatología , Desempeño Psicomotor/fisiología , Recompensa , Dopamina/metabolismo , Humanos , Movimientos Sacádicos/fisiologíaRESUMEN
BACKGROUND: Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD. METHODS: One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing. RESULTS: We show that the frequency of GBA1 mutations is much higher in this patient series than in typical late-onset patient cohorts. Furthermore, our results reveal that the most prevalent PD-associated GBA1 mutation is E326K, a variant that does not, when homozygous, cause GD. CONCLUSIONS: Our results confirm recent reports that the mutation, E326K, predisposes to PD and suggest that, in addition to reduced GBA1 activity, other molecular mechanisms may contribute to the development of the disease.
Asunto(s)
Glucosilceramidasa/genética , Enfermedad de Parkinson/genética , Adulto , Edad de Inicio , ADN/genética , Bases de Datos Genéticas , Exones/genética , Femenino , Enfermedad de Gaucher/epidemiología , Enfermedad de Gaucher/genética , Frecuencia de los Genes , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Leucocitos/enzimología , Enfermedad por Cuerpos de Lewy/genética , Enfermedad por Cuerpos de Lewy/patología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación/genética , Sistemas de Lectura Abierta/genética , Enfermedad de Parkinson/epidemiología , Proteínas Serina-Treonina Quinasas/genética , Análisis de Secuencia de ADN , Ubiquitina-Proteína Ligasas/genética , Reino Unido/epidemiología , Población Blanca , Adulto JovenAsunto(s)
Tronco Encefálico/parasitología , Encefalitis/diagnóstico , Encefalitis/parasitología , Neuroesquistosomiasis/diagnóstico , Esquistosomiasis mansoni/diagnóstico , Adulto , Animales , Tronco Encefálico/patología , Diagnóstico Diferencial , Humanos , Masculino , Neuroesquistosomiasis/parasitología , Esquistosomiasis mansoni/parasitologíaRESUMEN
This case report describes an atypical presentation of eclampsia. A 26-year-old lady presented 5 days' postpartum with a series of grand mal seizures after an uneventful pregnancy and delivery. An MRI scan of the brain showed areas of low signal involving cerebral white matter and right cerebellum. Within 2 weeks, all symptoms and radiologic abnormalities had resolved.
Asunto(s)
Eclampsia/complicaciones , Eclampsia/diagnóstico , Epilepsia Tónico-Clónica/etiología , Trastornos Puerperales/diagnóstico , Femenino , Humanos , Embarazo , RecurrenciaAsunto(s)
Complicaciones de la Diabetes , Hiperpotasemia/complicaciones , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Diuréticos/efectos adversos , Combinación de Medicamentos , Humanos , Hiperpotasemia/inducido químicamente , Factores de Riesgo , Espironolactona/efectos adversosRESUMEN
Cerebrospinal fluid (CSF) analysis of pterin and monamine metabolites was performed before and after an attack in a patient with paroxysmal exercise-induced dystonia. A twofold increase in CSF homovanillic acid and 5-hydroxyindoleacetic acid after an attack was measured. This finding lends support to the hypothesis that increased dopaminergic transmission contributes to the clinical features of the hyperkinetic movement disorders.
Asunto(s)
Dopamina/fisiología , Distonía/fisiopatología , Ejercicio Físico/fisiología , Adulto , Distonía/diagnóstico , Ácido Homovanílico/líquido cefalorraquídeo , Humanos , Ácido Hidroxiindolacético/líquido cefalorraquídeo , Masculino , Examen Neurológico , Transmisión Sináptica/fisiologíaRESUMEN
Paroxysmal kinesigenic dyskinesia (PKD) is characterised by paroxysms of choreic, dystonic, ballistic, or athetoid movements. The attacks typically last seconds to minutes in duration and are induced by sudden voluntary movement. PKD loci have been identified on chromosome 16. We present the clinical and genetic details of two British and an Indian family with PKD. Linkage to the PKD loci on chromosome 16 has been excluded in one of these families, providing evidence for a third loci for PKD. Detailed clinical descriptions highlight the presence of both adolescent and infantile seizures in some of the PKD families. This study attempts to clarify the relationship of adolescent and infantile seizures to PKD and provides evidence that PKD is both genetically and clinically heterogeneous.