RESUMEN
Insular degeneration has been linked to symptoms of frontotemporal dementia (FTD). Presented in this case is a patient exhibiting semantic variant primary progressive aphasia, behavioral disturbance. Upon autopsy, he was found to have severe insular atrophy. In addition, selective serotonin reuptake inhibitors were ineffective in reducing symptoms of obsessive-compulsive behaviors or emotional blunting. This case suggests that Seeley et al.'s (2007 , Alzheimer Disease & Associated Disorders, 21, S50) hypothesis that von Economo neurons and fork cell-rich brain regions, particularly in the insula, are targeted in additional subtypes of FTD beyond the behavioral variant.
Asunto(s)
Afasia Progresiva Primaria/patología , Corteza Cerebral/patología , Demencia Frontotemporal/patología , Afasia Progresiva Primaria/fisiopatología , Afasia Progresiva Primaria/psicología , Atrofia , Autopsia , Síntomas Conductuales , Corteza Cerebral/fisiopatología , Conducta Compulsiva/patología , Demencia Frontotemporal/fisiopatología , Demencia Frontotemporal/psicología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , SemánticaRESUMEN
OBJECTIVE: The objective of this study was to identify the relation between the cognitive benefit seen with the cholinesterase inhibitor metrifonate and changes in brain metabolism as visualized with [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). BACKGROUND: The regional metabolic correlates of treatment with cholinesterase inhibitors are poorly understood. METHODS: Six patients with mild to moderate Alzheimer disease (AD) were evaluated before and after treatment with the long-lasting cholinesterase inhibitor metrifonate. Patients were given 60 or 80 mg of metrifonate per day (based on weight) for 6 to 12 weeks. Clinical evaluations included the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory. Imaging was carried out using FDG-PET. The PET studies, registered to a probabilistic anatomic atlas, were normalized across the group's mean intensity levels and subjected to voxel-by-voxel subtraction of the posttreatment minus pretreatment studies. Subvolume thresholding corrected random lobar noise to produce a three-dimensional functional significance map. RESULTS: The criteria for cognitive improvement with treatment were met for the MMSE (>2 points improvement from baseline), and the drawing subscale of the ADAS-cog was significantly improved with treatment. The three-dimensional significance map revealed a significant metabolic increase of the dorsolateral frontoparietal network on the left and bilateral temporal cortex with metrifonate treatment. CONCLUSION: The clinical benefits observed in AD with cholinesterase inhibitor therapy are associated with a metabolic increase of heteromodal cognitive and medial temporal networks.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Encéfalo/fisiología , Inhibidores de la Colinesterasa/farmacología , Trastornos del Conocimiento/tratamiento farmacológico , Triclorfón/farmacología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Encéfalo/efectos de los fármacos , Trastornos del Conocimiento/etiología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Radiofármacos , Tomografía Computarizada de Emisión , Resultado del TratamientoRESUMEN
Parkinson's disease (PD) is a disabling neurodegenerative condition commonly complicated by the existence of comorbid depression. The prevalence rates of depression in this patient group have been reported to be as high as 40%. Currently, depression in PD is undertreated; there have been few controlled clinical trials of antidepressants in this patient group. Patients with PD are usually elderly and often administered a range of medication, therefore the choice of antidepressant must be undertaken with care. Tricyclic antidepressants (TCAs) have been studied in patients with PD and comorbid depression; however, the risk of anticholinergic side-effects means that their use is largely avoided. Selective serotonin reuptake inhibitors have comparable efficacy to the TCAs and a better tolerability profile in patients with depression; they are rapidly being considered as first-line therapy for PD patients with depression. Clinical studies in this patient group are warranted. This article reviews the characteristics of comorbid depression in patients with PD and discusses the treatment options available.
Asunto(s)
Trastorno Depresivo/tratamiento farmacológico , Enfermedad de Parkinson/psicología , Antidepresivos Tricíclicos/uso terapéutico , Trastorno Depresivo/complicaciones , Humanos , Inhibidores de la Monoaminooxidasa/uso terapéutico , Enfermedad de Parkinson/fisiopatología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
Alzheimer's disease affects multiple domains of human brain function and has neuropsychological, neuropsychiatric, and neurologic manifestations. Behavioral changes should be assessed as part of a comprehensive evaluation of the effects of cholinergic treatment of Alzheimer's disease. The psychometric properties, origin, source of behavioral information, content, and administration requirements of tools used to assess behavior in Alzheimer's disease affect the type of information garnered and the conclusions that can be derived. Assessment of drug-related behavioral changes can be affected by spontaneous remission of neuropsychiatric symptoms, differing baseline severity of behavioral abnormalities, uncertain magnitude of expected treatment effects, and by the influence of disease stages, concurrent medications, and comorbid conditions. Cholinergic therapies ameliorate behavioral alteration in Alzheimer's disease, and changes in behavior should be monitored when such therapy is initiated.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Colinérgicos/uso terapéutico , Trastornos Mentales/diagnóstico , Trastornos Mentales/tratamiento farmacológico , Psicotrópicos/uso terapéutico , Anciano , Enfermedad de Alzheimer/psicología , Animales , Antipsicóticos/uso terapéutico , Inhibidores de la Colinesterasa/uso terapéutico , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/psicología , Comorbilidad , Humanos , Trastornos Mentales/psicología , Pruebas Neuropsicológicas/estadística & datos numéricos , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Psicometría , Reproducibilidad de los ResultadosRESUMEN
The authors report on a series of patients with idiopathic Parkinson's disease (IPD) who underwent stereotactic radiofrequency (RF) pallidotomies, three of whom suffered delayed postoperative strokes. These three belonged to a group consisting of 42 patients with medically intractable IPD in whom 50 pallidotomies were performed. All three patients had significant previous vascular disease and were in a high-risk group for cerebral infarction. A postoperative magnetic resonance (MR) image was obtained immediately after the pallidotomy was performed to document the placement of the RF lesion and to rule out any hematoma. The delayed strokes occurred on postoperative Days 10, 51, and 117 in patients with previous vascular disease (Group 1, 11 patients). No strokes occurred in the group with the vascular disease risk factor (Group 2, 11 patients) or in the group with no risk factors for vascular disease (Group 3, 20 patients). This observation is statistically significant (p < 0.05). The T2-weighted MR images showed the lesions as high-intensity signals extending to the posterior limb of the internal capsule ipsilateral to the pallidotomy site. The poststroke T1-weighted images obtained in two patients showed persistent contrast enhancement of the RF lesion and no enhancement around the stroke lesion. Clinically and radiographically, these discrete new lesions represent delayed infarctions, suggesting that RF lesioning can induce delayed injury in adjacent tissue. Patients with previously identified vasculopathy may be at risk for delayed capsular infarction following RF pallidotomy.
Asunto(s)
Infarto Cerebral/etiología , Globo Pálido/cirugía , Enfermedad de Parkinson/cirugía , Radiocirugia/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , Trastornos Cerebrovasculares/etiología , Medios de Contraste , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/cirugía , Femenino , Estudios de Seguimiento , Hematoma/etiología , Humanos , Aumento de la Imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Cuidados Posoperatorios , Radiocirugia/métodos , Estudios Retrospectivos , Factores de Riesgo , Enfermedades Vasculares/complicacionesRESUMEN
A series of discrete, parallel frontal-subcortical circuits have been demonstrated to link specific areas of the frontal lobe to areas within the basal ganglia and thalamus. A variety of circuit-specific behaviors can be described involving the dorsolateral prefrontal, orbitofrontal and anterior cingulate circuits. Interruptions or imbalance occurring at various levels within these closed looped circuits is felt to underlie the characteristic behavioral patterns seen. The intricate neurochemical arrangement of the striatum and the complex neurotransmitter interactions that occur within these key subcortical structures from the basis for modulatory influences that can affect these circuits.
Asunto(s)
Conducta Apetitiva/fisiología , Ganglios Basales/fisiología , Lóbulo Frontal/fisiología , Giro del Cíngulo/fisiología , Motivación , Corteza Prefrontal/fisiología , Conducta Social , Núcleos Talámicos/fisiología , Animales , Ganglios Basales/anatomía & histología , Mapeo Encefálico , Lóbulo Frontal/anatomía & histología , Giro del Cíngulo/anatomía & histología , Humanos , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Neurotransmisores/fisiología , Corteza Prefrontal/anatomía & histología , Transmisión Sináptica/fisiología , Núcleos Talámicos/anatomía & histologíaRESUMEN
Investigators have reported high sensitivity and specificity values for single photon emission computerized tomography (SPECT) when distinguishing Alzheimer's disease (AD) patients from normal elderly controls or from selected patient groups. The role of SPECT in identifying AD among unselected patients with memory complaints requires investigation. We examined 139 consecutive patients with 99Tc-HMPAO SPECT. NINCDS-ADRDA diagnoses were determined blind to SPECT results, and scans were read and classified by visual inspection blind to clinical diagnoses. Bilateral temporoparietal hypoperfusion (TP) occurred in 75% of probable, 65% of possible, and 45% of unlikely AD patients, yielding a sensitivity of 75% and a specificity of 52% when comparing probable AD versus unlikely AD groups. A positive predictive value of 78% was obtained based on a 69% prevalence of AD in our total clinic population. Patients with false-positive results included a variety of dementing illnesses; all patients with bilateral hypoperfusion had dementia. A pattern of TP on SPECT scans is seen in most patients with AD, but could be found in other dementias as well and cannot be regarded as specific to AD. Reduced TP perfusion discriminated between demented and nondemented individuals. Further strategies for SPECT interpretation that improve diagnostic specificity should be sought.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Demencia/diagnóstico por imagen , Compuestos de Organotecnecio , Oximas , Tomografía Computarizada de Emisión de Fotón Único/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/fisiopatología , Demencia/fisiopatología , Demencia Vascular/diagnóstico por imagen , Demencia Vascular/fisiopatología , Diagnóstico Diferencial , Dominancia Cerebral/fisiología , Humanos , Lóbulo Parietal/irrigación sanguínea , Lóbulo Parietal/diagnóstico por imagen , Valores de Referencia , Flujo Sanguíneo Regional/fisiología , Sensibilidad y Especificidad , Exametazima de Tecnecio Tc 99m , Lóbulo Temporal/irrigación sanguínea , Lóbulo Temporal/diagnóstico por imagenRESUMEN
Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study. Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimer's disease (AD) (n = 18), Parkinson's disease (PD) (n = 5), or progressive supranuclear palsy (PSP) (n = 1) were studied. Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250 x magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of > 6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivity/specificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs (chi 2 = 5.48, p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement.