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The aims of the study were to assess empathy deficit and neuronal correlates in logopenic primary progressive aphasia (lv-PPA) and compare these data with those deriving from amnesic Alzheimer's disease (AD). Eighteen lv-PPA and thirty-eight amnesic AD patients were included. Empathy in both cognitive and affective domains was assessed by Informer-rated Interpersonal Reactivity Index (perspective taking, PT, and fantasy, FT, for cognitive empathy; empathic concern, EC, and personal distress, PD, for affective empathy) before (T0) and after (T1) cognitive symptoms' onset. Emotion recognition was explored through the Ekman 60 Faces Test. Cerebral FDG-PET was used to explore neural correlates underlying empathy deficits. From T0 to T1, PT scores decreased, and PD scores increased in both lv-PPA (PT z = -3.43, p = 0.001; PD z = -3.62, p < 0.001) and in amnesic AD (PT z = -4.57, p < 0.001; PD z = -5.20, p < 0.001). Delta PT (T0-T1) negatively correlated with metabolic disfunction of the right superior temporal gyrus, fusiform gyrus, and middle frontal gyrus (MFG) in amnesic AD and of the left inferior parietal lobule (IPL), insula, MFG, and bilateral superior frontal gyrus (SFG) in lv-PPA (p < 0.005). Delta PD (T0-T1) positively correlated with metabolic disfunction of the right inferior frontal gyrus in amnesic AD (p < 0.001) and of the left IPL, insula, and bilateral SFG in lv-PPA (p < 0.005). Lv-PPA and amnesic AD share the same empathic changes, with a damage of cognitive empathy and a heightening of personal distress over time. The differences in metabolic disfunctions correlated with empathy deficits might be due to a different vulnerability of specific brain regions in the two AD clinical presentations.
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BACKGROUND: The early differential diagnosis among neurodegenerative parkinsonian disorders becomes essential to set up the correct clinical-therapeutic approach. The increased utilization of [18F] fluoro-deoxy-glucose positron emission tomography (FDG PET) and the pressure for cost-effectiveness request a systematic evaluation and a validation of its utility in clinical practice. This retrospective study aims to consider the contribution, in terms of increasing accuracy and increasing diagnostic confidence, of voxel-based FDG PET analyses in the differential diagnosis of these disorders, including Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and cortico-basal syndrome. METHOD: Eighty-three subjects with a clinically confirmed diagnosis of degenerative parkinsonian disorders who underwent FDG brain PET/CT were selected. A voxel-based analysis was set up using statistical parametric mapping (SPM) on MATLAB to produce maps of brain hypometabolism and relative hypermetabolism. Four nuclear physicians (two expert and two not expert), blinded to the patients' symptoms, other physicians' evaluations, and final clinical diagnosis, independently evaluated all data by visual assessment and by adopting metabolic maps. RESULTS: In not-expert evaluators, the support of both hypometabolism and hypermetabolism maps results in a significant increase in diagnostic accuracy as well as clinical confidence. In expert evaluators, the increase in accuracy and in diagnostic confidence is mainly supported by hypometabolism maps alone. CONCLUSIONS: In this study, we demonstrated the additional value of combining voxel-based analyses with qualitative assessment of brain PET images. Moreover, maps of relative hypermetabolism can also make their contribution in clinical practice, particularly for less experienced evaluators.
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Atrofia de Múltiples Sistemas , Trastornos Parkinsonianos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Diagnóstico Diferencial , Fluorodesoxiglucosa F18 , Humanos , Atrofia de Múltiples Sistemas/diagnóstico por imagen , Trastornos Parkinsonianos/diagnóstico por imagen , Trastornos Parkinsonianos/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones/métodos , Estudios RetrospectivosRESUMEN
We aimed to identify features associated with different disease trajectories in Alzheimer's disease (AD)-related primary progressive aphasia (PPA). We considered 23 patients diagnosed with AD-related PPA. All patients underwent neuropsychological evaluation, 18F-Fluorodeoxyglucose-PET brain scan, CSF biomarkers measurement and APOE genotype analysis at baseline and underwent neurological follow-up for a mean time of 3 years. Patients who progressed to total loss of speech (TLoS+) had greater impairment in writing and higher t-tau concentration as compared to TLoS- patients. Patients who progressed to loss of functional autonomy (LoFA+) had greater impairment in single-word comprehension as compared to patients who maintained autonomy in self-care. Furthermore, 18F-FDG-PET SPM analyses revealed different brain metabolic patterns between TLoS+ and TLoS- and between LoFA+ and LoFA-. In conclusion, linguistic profile, CSF t-tau and brain metabolic pattern might be useful tools to predict progression to total loss of speech and loss of functional autonomy in AD-related PPA patients.
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Enfermedad de Alzheimer , Afasia Progresiva Primaria , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Afasia Progresiva Primaria/diagnóstico , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Humanos , Tomografía de Emisión de Positrones , Habla , Proteínas tau/metabolismoRESUMEN
Empathy is the ability to understand (cognitive empathy) and to feel (affective empathy) what others feel. The aim of the study was to assess empathy deficit and neuronal correlates in Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) dementia. Twenty-four SCD, 41 MCI and 46 CE patients were included. Informer-rated Interpersonal Reactivity Index was used to explore cognitive (Perspective Taking-PT, Fantasy-FT) and affective (Empathic Concern-EC, Personal Distress-PD) empathy, before (T0) and after (T1) cognitive symptoms' onset. Emotion recognition ability was tested through Ekman-60 Faces Test. Cerebral FDG-PET SPM analysis was used to explore neural correlates underlying empathy deficits. FT-T1 scores were lower in AD compared to SCD (13.0 ± 8.0 vs 19.1 ± 4,7 p = 0.008), PD-T1 score were higher in AD compared to MCI and to SCD (27.00 ± 10.00 vs 25.3 ± 5.9 vs 20.5 ± 5.6, p = 0.001). A positive correlation was found between PT-T1 and metabolic disfunction of right middle gyrus (MFG) in MCI and AD. In AD group, a positive correlation between PT-T1 and insula and superior temporal gyrus (STG) metabolism was detected. A negative correlation was found between PD-T1 and superior parietal lobule metabolism in MCI, and between PD-T1 and STG metabolism in AD. Impairment of cognitive empathy starts at MCI stage. Increase of PD starts from preclinical phases and seems to be to be dissociated from cognitive decline. Loss of PT is related to a progressive involvement starting from right MFG in prodromal stage, extending to insula and STG in dementia. Heightened emotional contagion is probably related to derangement of mirror neurons systems in parietal regions in prodromal stages, and to impairment of temporal emotion inhibition system in advanced phases. Further studies are needed to clarify if alterations in emotional contagion might be a predictive feature of a cognitive decline driven by AD.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Neuronas Espejo , Enfermedad de Alzheimer/metabolismo , Disfunción Cognitiva/metabolismo , Empatía , Humanos , Tomografía de Emisión de Positrones , Síntomas ProdrómicosRESUMEN
BACKGROUND: Alzheimer's disease (AD) diagnosis can be hindered by amyloid biomarkers discordances. OBJECTIVE: We aim to interpret discordances between amyloid positron emission tomography (Amy-PET) and cerebrospinal fluid (CSF) (Aß42 and Aß42/40), using Amy-PET semiquantitative analysis, [18F]fluorodeoxyglucose (FDG)-PET pattern, and CSF assays. METHOD: Thirty-six subjects with dementia or mild cognitive impairment, assessed by neuropsychological tests, structural and functional imaging, and CSF assays (Aß42, Aß42/40, p-tau, t-tau), were retrospectively examined. Amy-PET and FDG-PET scans were analyzed by visual assessment and voxel-based analysis. SUVR were calculated on Amy-PET scans. RESULTS: Groups were defined basing on the agreement among CSF Aß42 (A), CSF Aß42/40 Ratio (R), and Amy-PET (P) dichotomic results ( ±). In discordant groups, CSF assays, Amy-PET semiquantification, and FDG-PET patterns supported the diagnosis suggested by any two agreeing amyloid biomarkers. In groups with discordant CSF Aß42, the ratio always agrees with Amy-PET results, solving both false-negative and false-positive Aß42 results, with Aß42 levels close to the cut-off in A + R-P- subjects. The A + R + P- group presented high amyloid deposition in relevant areas, such as precuneus, posterior cingulate cortex (PCC) and dorsolateral frontal inferior cortex at semiquantitative analysis. CONCLUSION: The amyloid discordant cases could be overcome by combining CSF Aß42, CSF ratio, and Amy-PET results. The concordance of any 2 out of the 3 biomarkers seems to reveal the remaining one as a false result. A cut-off point review could avoid CSF Aß42 false-negative results. The regional semiquantitative Amy-PET analysis in AD areas, such as precuneus and PCC, could increase the accuracy in AD diagnosis.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico por imagen , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico por imagen , Humanos , Fragmentos de Péptidos/líquido cefalorraquídeo , Tomografía de Emisión de Positrones , Estudios Retrospectivos , Proteínas tau/líquido cefalorraquídeoRESUMEN
We aimed to detail language profiles, brain metabolic patterns and proportion of Alzheimer's disease biomarkers in a cohort of patients with mixed primary progressive aphasia (mPPA). We considered 58 patients with PPA: 10 with non-fluent/agrammatic variant (nfvPPA), 16 with semantic variant (svPPA), 21 with logopenic variant (lvPPA) and 9 with mPPA. Patients with mPPA were further classified as 4 nf/lvPPA (with prevailing features for nfvPPA and lvPPA) and 5 s/lvPPA (with prevailing features for svPPA and lvPPA). Nf/lvPPA patients were characterized by higher proportion of Naming impairment compared to nfvPPA and more frequent Grammatical Errors and Phonologic Errors than lvPPA. S/lvPPA had higher proportion of impairment in Sentences Repetition compared to svPPA and in Single-word Comprehension compared to lvPPA. 100% of nf/lvPPA and 40% of s/lvPPA had Aß positive biomarkers. Brain hypometabolic pattern in Nf/lvPPA was consistent with lvPPA, while s/lvPPA had a brain metabolism resembling svPPA. We concluded that nf/lvPPA patients might be considered as PPA variant due to Alzheimer's disease and s/lvPPA group mainly included patients with svPPA.
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Péptidos beta-Amiloides/metabolismo , Afasia Progresiva Primaria/metabolismo , Afasia Progresiva Primaria/psicología , Encéfalo/metabolismo , Lenguaje , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/psicología , Afasia Progresiva Primaria/diagnóstico , Biomarcadores/metabolismo , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , HablaRESUMEN
BACKGROUND: Discordance among amyloid biomarkers is a challenge to overcome in order to increase diagnostic accuracy in dementia. OBJECTIVES: 1) To verify that cerebrospinal fluid (CSF) Aß42/Aß40 ratio (AßR) better agrees with Amyloid PET (Amy-PET) results compared to CSF Aß42; 2) to detect differences among concordant positive, concordant negative, and discordant cases, basing the concordance definition on the agreement between CSF AßR and Amy-PET results; 3) to define the suspected underlying pathology of discordant cases using in vivo biomarkers. METHOD: We retrospectively enrolled 39 cognitively impaired participants in which neuropsychological tests, apolipoprotein E genotype determination, TC/MRI, FDG-PET, Amy-PET, and CSF analysis had been performed. In all cases, CSF analysis was repeated using the automated Lumipulse method. In discordant cases, FDG-PET scans were evaluated visually and using automated classifiers. RESULTS: CSF AßR better agreed with Amy-PET compared to CSF Aß42 (Cohen's K 0.431 versus 0.05). Comparisons among groups did not show any difference in clinical characteristics except for age at symptoms onset that was higher in the 6 discordant cases with abnormal CSF AßR values and negative Amy-PET (CSF AßR+/AmyPET-). FDG-PET and all CSF markers (Aß42, AßR, p-Tau, t-Tau) were suggestive of Alzheimer's disease (AD) in 5 of these 6 cases. CONCLUSION: 1) CSF AßR is the CSF amyloid marker that shows the better level of agreement with Amy-PET results; 2) The use of FDG-PET and CSF-Tau markers in CSFAßR+/Amy-PET-discordant cases can support AD diagnosis; 3) Disagreement between positive CSF AßR and negative Amy-PET in symptomatic aged AD patients could be due to the variability in plaques conformation and a negative Amy-PET scan cannot be always sufficient to rule out AD.
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Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico por imagen , Péptidos beta-Amiloides/líquido cefalorraquídeo , Pruebas Neuropsicológicas , Fragmentos de Péptidos/líquido cefalorraquídeo , Anciano , Enfermedad de Alzheimer/psicología , Biomarcadores/líquido cefalorraquídeo , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Proteínas tau/líquido cefalorraquídeoAsunto(s)
Encéfalo/fisiopatología , Electroencefalografía/métodos , Demencia Frontotemporal/diagnóstico por imagen , Encefalitis Límbica/diagnóstico por imagen , Trastornos de la Memoria/etiología , Pólipos Adenomatosos/diagnóstico por imagen , Anciano , Diagnóstico Diferencial , Humanos , Encefalitis Límbica/diagnóstico , Encefalitis Límbica/patología , Imagen por Resonancia Magnética , Masculino , Enfermedad de Pick , Tomografía de Emisión de PositronesRESUMEN
Damage to nonmotor dopamine (DA)-mediated frontostriatal circuits has been proposed as the main pathophysiological basis of cognitive dysfunction in Parkinson's disease (PD). In the present study, 18 early nondemented drug naive PD patients were investigated, by dual-tracer N-ω-fluoropropyl-2ß-carbomethoxy-3ß-4-[123I]iodophenyl-nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT)/[18F] fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging, to test whether an early and not yet treatment-modulated relation exists between cognitive functions, caudate nucleus (CN) DA impairment and brain metabolism (CMRglc) in associative frontostriatal circuits. Verbal fluency performance correlated with DA impairment in CN, and with CMRglc in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Further, CMRglc in orbitofrontal cortex, DLPFC, and ACC was shown to be early modulated by the level of DA impairment in CN. The present study demonstrates in vivo the early functional disruption of nonmotor frontostriatal circuits in PD. The effect of CN DA impairment on DLPFC and ACC metabolism is proposed as a possible early pathophysiological and functional substrate for executive dysfunction in PD.
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Núcleo Caudado/metabolismo , Trastornos del Conocimiento/etiología , Dopamina/metabolismo , Giro del Cíngulo/metabolismo , Enfermedad de Parkinson/complicaciones , Corteza Prefrontal/metabolismo , Anciano , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/patología , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/patología , Progresión de la Enfermedad , Femenino , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Tomografía de Emisión de Positrones , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/patología , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Rebuilding brain structure and neural circuitries by transplantation of fetal tissue is a strategy to repair the damaged nervous system and is currently being investigated using striatal primordium in Huntington's disease (HD) patients. Four HD patients underwent bilateral transplantation with human fetal striatal tissues (9-12 week gestation). Small blocks of whole ganglionic eminencies were processed to obtain cell suspension and then stereotactically grafted in the caudate head and in the putamen. Follow-up period ranged between 18 and 34 months (mean, 24.7 months). Surgery was uneventful. Starting from the fourth month after grafting, neo-generation of metabolically active tissue with striatal-like MRI features was observed in 6 out of 8 grafts. The increase in D2 receptor binding suggested striatal differentiation of the neo-generated tissue in 3 patients. New tissue, connecting the developing grafts with the frontal cortex and, in one case, with the ventral striatum, was also observed. The new tissue growth halted after the ninth month post transplantation. All patients showed stabilization or improvement in some neurological indices. No clinical and imaging signs, suggestive of graft uncontrolled growth, were seen. This study provides the first evidence in humans that neuroblasts of a striatal primordium can develop and move into the brain after neurotransplantation. Primordium development resulted in the building of a new structure with the same imaging features as the corresponding mature structure, combined with short- and long-distance targeted migration of neuroblasts. The results of this study support both the reconstructive potential of fetal tissue and the remarkably retained plasticity of adult brain. Further studies are necessary to assess the clinical efficacy of the human fetal striatal transplantation.
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Trasplante de Tejido Encefálico/métodos , Cuerpo Estriado/trasplante , Enfermedad de Huntington/fisiopatología , Enfermedad de Huntington/cirugía , Adulto , Movimiento Celular/fisiología , Cuerpo Estriado/citología , Cuerpo Estriado/diagnóstico por imagen , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Feto , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Regulación de la Expresión Génica/fisiología , Antígenos HLA/metabolismo , Humanos , Enfermedad de Huntington/diagnóstico por imagen , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Examen Neurológico/métodos , Unión Proteica/fisiología , ARN Mensajero/metabolismo , Receptores de Dopamina D2/metabolismo , Índice de Severidad de la Enfermedad , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
PURPOSE: The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients. METHODS: Twenty-six de novo untreated PD patients were scanned with (123)I-FP-CIT SPECT and (18)F-FDG PET. The dopaminergic impairment was measured with putaminal (123)I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP(OSEM)) and the least-squares (LS) method (BP(LS)). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc. RESULTS: The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP(OSEM) and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP(LS) and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p < 0.05, corrected for multiple comparison). CONCLUSIONS: Putaminal BP(LS) is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects.
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Encéfalo/metabolismo , Dopamina/metabolismo , Enfermedad de Parkinson/metabolismo , Algoritmos , Encéfalo/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18/metabolismo , Humanos , Procesamiento de Imagen Asistido por Computador , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Actividad Motora , Neostriado/metabolismo , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/fisiopatología , Tomografía de Emisión de Positrones , Tomografía Computarizada de Emisión de Fotón Único , Tropanos/metabolismoRESUMEN
Replacement of damaged neuronal population by fetal tissue transplantation represents a potential treatment for neurodegenerative diseases. Consistent success has been achieved with fetal striatal transplantation in Huntington's disease animal models and patients. We report the neo-generation of metabolically active tissue with striatum-like imaging features after transplantation of striatal primordia in a patient with Huntington's disease. This study represents the first "in vivo" demonstration that a human striatal anlagen, transplanted into the adult human brain, is able to progress in its development and to generate a new anatomical structure in the host, without evidence of neoplasia or teratoma.
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Trasplante de Tejido Encefálico/métodos , Cuerpo Estriado/embriología , Cuerpo Estriado/trasplante , Trasplante de Tejido Fetal/métodos , Supervivencia de Injerto/fisiología , Enfermedad de Huntington/terapia , Adulto , Células Cultivadas , Cuerpo Estriado/metabolismo , Metabolismo Energético/fisiología , Femenino , Lateralidad Funcional/fisiología , Humanos , Enfermedad de Huntington/patología , Enfermedad de Huntington/fisiopatología , Imagen por Resonancia Magnética , Plasticidad Neuronal/fisiología , Neuronavegación , Tomografía de Emisión de Positrones , Técnicas Estereotáxicas , Resultado del TratamientoRESUMEN
PURPOSE: The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-omega-fluoropropyl-2beta-carbomethoxy-3beta-4-[(123)I]iodophenyl-nortropane ((123)I-FP-CIT) binding in de novo Parkinson's disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease. METHODS: Thirty-six de novo PD patients underwent (123)I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal (123)I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BP(FBP), BP(OSEM), BP(LS)). RESULTS: The range of values of striatal BP(LS) was significantly greater than BP(FBP) and BP(OSEM). For all striatal regions, estimates of BP(FBP) correlated well with BP(OSEM) (r = 0.84) and with BP(LS) (r = 0.64); BP(OSEM) correlated significantly with BP(LS) (r = 0.76). A good correlation was found between putaminal BP(LS) and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r = -0.46, r = -0.42, r = -0.39, respectively). Neither putaminal BP(FBP) nor putaminal BP(OSEM) correlated with any of these motor scores. CONCLUSIONS: In de novo PD patients, (123)I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of (123)I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity.
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Enfermedad de Parkinson/metabolismo , Tropanos/metabolismo , Anciano , Anciano de 80 o más Años , Cuerpo Estriado/metabolismo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Actividad Motora , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Tomografía Computarizada de Emisión de Fotón ÚnicoAsunto(s)
Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Síndrome del Cromosoma X Frágil/complicaciones , Trastornos Heredodegenerativos del Sistema Nervioso/diagnóstico por imagen , Trastornos Heredodegenerativos del Sistema Nervioso/patología , Anciano , Ataxia/diagnóstico por imagen , Ataxia/genética , Ataxia/patología , Atrofia/diagnóstico por imagen , Atrofia/genética , Atrofia/patología , Enfermedades de los Ganglios Basales/genética , Unión Competitiva/fisiología , Encéfalo/fisiopatología , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/patología , Cuerpo Estriado/fisiopatología , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Tractos Extrapiramidales/diagnóstico por imagen , Tractos Extrapiramidales/patología , Tractos Extrapiramidales/fisiopatología , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Mesencéfalo/diagnóstico por imagen , Mesencéfalo/patología , Mesencéfalo/fisiopatología , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Valor Predictivo de las Pruebas , Radiografía , Radioisótopos , Receptores Dopaminérgicos/metabolismo , Síndrome , Tomografía Computarizada de Emisión de Fotón Único , Temblor/diagnóstico por imagen , Temblor/genética , Temblor/patologíaRESUMEN
PURPOSE: The clinical potential of striatal imaging with dopamine transporter (DAT) SPECT tracers is hampered by the limited capability to recover activity concentration ratios due to partial volume effects (PVE). We evaluated the accuracy of a least squares method that allows retrieval of activity in regions of interest directly from projections (LS-ROI). METHODS: An Alderson striatal phantom was filled with striatal to background ratios of 6:1, 9:1 and 28:1; the striatal and background ROIs were drawn on a coregistered X-ray CT of the phantom. The activity ratios of these ROIs were derived both with the LS-ROI method and with conventional SPECT EM reconstruction (EM-SPECT). Moreover, the two methods were compared in seven patients with motor symptoms who were examined with N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) (FP-CIT) SPECT, calculating the binding potential (BP). RESULTS: In the phantom study, the activity ratios obtained with EM-SPECT were 3.5, 5.3 and 17.0, respectively, whereas the LS-ROI method resulted in ratios of 6.2, 9.0 and 27.3, respectively. With the LS-ROI method, the BP in the seven patients was approximately 60% higher than with EM-SPECT; a linear correlation between the LS-ROI and the EM estimates was found (r=0.98, p=0.03). CONCLUSION: The LS-ROI PVE correction capability is mainly due to the fact that the ill-conditioning of the LS-ROI approach is lower than that of the EM-SPECT one. The LS-ROI seems to be feasible and accurate in the examination of the dopaminergic system. This approach can be fruitful in monitoring of disease progression and in clinical trials of dopaminergic drugs.
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Trazadores Radiactivos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tropanos/farmacología , Adulto , Anciano , Algoritmos , Dopamina/metabolismo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Modelos Biológicos , Modelos Estadísticos , Fantasmas de Imagen , Factores de TiempoRESUMEN
We describe and present a videotape of a 57-year-old woman admitted to our Neurological Clinic at 46 years of age due to extrapyramidal manifestations suggesting Parkinson's disease (PD) and with a brain magnetic resonance imaging scan showing multi-infarctual leukoencephalopathy. Various investigations led to the diagnosis of Anderson Fabry's disease (AFD). We discuss the possibility of correlation between the patient's parkinsonism and AFD.
Asunto(s)
Enfermedad de Fabry/diagnóstico , Trastornos Parkinsonianos/diagnóstico , Encéfalo/patología , Infarto Cerebral/diagnóstico , Infarto Cerebral/genética , Cromosomas Humanos X , Demencia por Múltiples Infartos/diagnóstico , Demencia por Múltiples Infartos/genética , Diagnóstico Diferencial , Enfermedad de Fabry/genética , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Examen Neurológico , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/genética , Trastornos Parkinsonianos/genética , Linaje , Mutación Puntual , Estadística como Asunto , Grabación de Cinta de Video , alfa-Galactosidasa/genéticaRESUMEN
Previous positron emission tomography (PET) studies with fluorodeoxglucose (FDG) as tracer in healthy elders showed that the epsilon4 allele of the apolipoprotein E (ApoE) gene is disruptive to cerebral glucose metabolism (rCMRglu), possibly through the interaction with the aging process. The present study was aimed at assessing whether this interaction occurs in patients with Alzheimer's disease (AD). Eight-six AD patients, including 40 ApoE4 carriers and 46 non-carriers, underwent (18)F-FDG PET scanning at rest. ApoE groups were comparable for age, gender, age at onset and disease duration. SPM'99 was used to assess rCMRGlu correlations with age, differences between ApoE groups and ApoE by age interaction, correcting for disease severity. Results were reported at P<0.001, uncorrected. Correlations between age and rCMRGlu confirmed the well-known negative relationship for both groups. Lower rCMRGlu was found within the frontal and cingulate areas for ApoE4 carriers as compared with the non-carriers. Additionally, a significant ApoE by age interaction was detected in the frontal and anterior cingulate cortex, with the ApoE4 carriers having a steeper regression slope with respect to the non-carriers. These results indicate that age-related regional rCMRglu decreases within the frontal and anterior cingulate areas may be more severe in AD patients carrying the ApoE4 allele.
Asunto(s)
Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Glucemia/metabolismo , Encéfalo/diagnóstico por imagen , Metabolismo Energético/genética , Genotipo , Procesamiento de Imagen Asistido por Computador , Tomografía Computarizada de Emisión , Factores de Edad , Anciano , Anciano de 80 o más Años , Alelos , Enfermedad de Alzheimer/diagnóstico por imagen , Apolipoproteína E4 , Mapeo Encefálico , Cerebelo/diagnóstico por imagen , Dominancia Cerebral/fisiología , Metabolismo Energético/fisiología , Femenino , Fluorodesoxiglucosa F18 , Lóbulo Frontal/diagnóstico por imagen , Tamización de Portadores Genéticos , Giro del Cíngulo/diagnóstico por imagen , Humanos , Masculino , Corteza Motora/diagnóstico por imagen , Giro Parahipocampal/diagnóstico por imagen , FenotipoRESUMEN
UNLABELLED: The aim of this study was to investigate the effect of deep-brain stimulation of the subthalamic nucleus (STN) on regional cerebral blood flow (rCBF) throughout the entire brain volume in patients with Parkinson's disease and to evaluate which of the brain areas showing an rCBF increase during STN stimulation related significantly to the improvement in motor function. METHODS: Ten consecutive Parkinson's disease patients (6 men, 4 women; mean age +/- SD, 59 +/- 8 y) with bilateral STN stimulators underwent 3 rCBF SPECT examinations at rest: the first preoperatively and the second and third postoperatively (follow-up, 4.8 +/- 1.4 mo) with STN stimulators on and off, respectively. The motor unified Parkinson's disease rating scale, the Hoehn and Yahr disability scale, and the Schwab and England activities-of-daily-living scale were used to evaluate the clinical state under each condition. Statistical parametric mapping was used to investigate rCBF during STN stimulation in comparison with rCBF preoperatively and with STN stimulators off. Also evaluated with statistical parametric mapping was the relationship between rCBF and individual motor scores used as covariates of interest. RESULTS: STN stimulation significantly changed rCBF in the right pre-supplementary motor area (pre-SMA), anterior cingulate cortex, and dorsolateral prefrontal cortex and in the medial Brodmann's area 8 (BA8) as defined in the atlas of Talairach and Tournoux (P < 0.05 corrected for multiple comparisons). The rCBF in these areas increased from the preoperative condition to the stimulators-on condition and decreased again after the stimulators were switched off. A significant correlation was detected between the improvement in motor scores and the rCBF increase only in the right pre-SMA and in the anterior cingulate motor area (P < 0.005, uncorrected). CONCLUSION: According to the topographic organization of the primate STN, our study shows that stimulation of the STN leads to rCBF increases in the motor (pre-SMA), associative, and limbic territories (anterior cingulate) in the frontal cortex. The significant correlation between motor improvement and rCBF increase in the pre-SMA and the anterior cingulate motor area reinforces the hypothesis that STN stimulation in parkinsonian patients can potentiate the cortical areas participating in higher-order aspects of motor control.