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BACKGROUND AND OBJECTIVE: Patients with dementia with Lewy bodies perform worse than those with Alzheimer disease (AD) on tests of visual perception, but the clinical utility of these tests remains unknown because studies often had clinically diagnosed groups that may inadvertently cross-contaminate Lewy body disease (LBD) with pure AD pathology, used experimental tests not easily adaptable for clinical use, and had no way to examine relationships between the severity of LBD pathology and degree of cognitive impairment. Therefore, we sought to determine whether performance on a widely used clinical test of visuoperceptual ability effectively differentiates between patients with autopsy-confirmed LBD or AD and correlates with the severity of LBD pathology. METHODS: Patients with mild to moderate dementia (n = 42) and cognitively healthy controls (n = 22) performed a Fragmented Letters Test in which they identified letters of the alphabet that were randomly visually degraded by 70% and additional visuospatial and episodic memory tests. At autopsy, dementia cases were confirmed to have LBD (n = 19), all with concomitant AD, or only AD (n = 23). Severity of α-synuclein pathology in the hippocampus and neocortex was rated on an ordinal scale. RESULTS: Patients with LBD performed worse than those with AD (B = -2.80 ± 0.91, p = 0.009) and healthy controls (B = -3.34 ± 1.09, p = 0.01) on the Fragmented Letters Test after adjustment for age, sex, education, Mini-Mental State Examination score, and ability to name intact letters. Patients with AD did not differ from controls (B = -0.55 ± 1.08, p = 0.87). The test effectively distinguished between patients with LBD or AD with 73% sensitivity and 87% specificity, and the area under the curve in receiver operating characteristic analyses was 0.85 (95% CI 0.72-0.95), higher than for standard tests of visuospatial ability (Block Design; 0.72; CI 0.35-0.75) or memory (California Verbal Learning Test, trials 1-5; 0.55; CI 0.57-0.88). Fragmented Letters Test scores were negatively correlated with LBD pathology density ratings in hippocampus and neocortical regions (Spearman rs = -0.53 to -0.69). DISCUSSION: Fragmented Letters Test performance can effectively differentiate patients with LBD pathology from those with only AD pathology at a mild to moderate stage of dementia, even when LBD occurs with significant concomitant AD pathology, and may also be useful for gauging the severity of cortical α-synuclein pathology in those with LBD.
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Enfermedad de Alzheimer , Enfermedad por Cuerpos de Lewy , Humanos , Enfermedad de Alzheimer/patología , Enfermedad por Cuerpos de Lewy/complicaciones , alfa-Sinucleína/metabolismo , Cuerpos de Lewy/patología , Percepción VisualRESUMEN
BACKGROUND AND OBJECTIVE: Patients with earlier age at onset of sporadic Alzheimer disease (AD) are more likely than those with later onset to present with atypical clinical and cognitive features. We sought to determine whether this age-related clinical and cognitive heterogeneity is mediated by different topographic distributions of tau-aggregate neurofibrillary tangles (NFTs) or by variable amounts of concomitant non-AD neuropathology. METHODS: The relative distribution of NFT density in hippocampus and midfrontal neocortex was calculated, and α-synuclein, TAR DNA binding protein 43 (TDP-43), and microvascular copathologies were staged, in patients with severe AD and age at onset of 51-60 (n = 40), 61-70 (n = 41), and >70 (n = 40) years. Regression, mediation, and mixed effects models examined relationships of pathologic findings with clinical features and longitudinal cognitive decline. RESULTS: Patients with later age at onset of AD were less likely to present with nonmemory complaints (odds ratio [OR] 0.46 per decade, 95% confidence interval [CI] 0.22-0.88), psychiatric symptoms (ß = -0.66, 95% CI -1.15 to -0.17), and functional impairment (ß = -1.25, 95% CI -2.34 to -0.16). TDP-43 (OR 2.00, 95% CI 1.23-3.35) and microvascular copathology (OR 2.02, 95% CI 1.24-3.40) were more common in later onset AD, and α-synuclein copathology was not related to age at onset. NFT density in midfrontal cortex (ß = -0.51, 95% CI -0.72 to -0.31) and midfrontal/hippocampal NFT ratio (ß = -0.18, 95% CI -0.26 to -0.10) were lower in those with later age at onset. Executive function (ß = 0.48, 95% CI 0.09-0.90) and visuospatial cognitive deficits (ß = 0.97, 95% CI 0.46-1.46) were less impaired in patients with later age at onset. Mediation analyses showed that the effect of age at onset on severity of executive function deficits was mediated by midfrontal/hippocampal NFT ratio (ß = 0.21, 95% CI 0.08-0.38) and not by concomitant non-AD pathologies. Midfrontal/hippocampal NFT ratio also mediated an association between earlier age at onset and faster decline on tests of global cognition, executive function, and visuospatial abilities. DISCUSSION: Worse executive dysfunction and faster cognitive decline in people with sporadic AD with earlier rather than later age at onset is mediated by greater relative midfrontal neocortical to hippocampal NFT burden and not by concomitant non-AD neuropathology.
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Enfermedad de Alzheimer , Neocórtex , Edad de Inicio , Enfermedad de Alzheimer/patología , Autopsia , Humanos , Neocórtex/patología , Ovillos Neurofibrilares/patología , Proteínas tau/metabolismoRESUMEN
Hydrophilic polymers are commonly used as coatings on intravascular medical devices. As intravascular procedures continue to increase in frequency, the risk of embolization of this material throughout the body has become evident. These emboli may be discovered incidentally but can result in serious complications including death. Here, we report the first two cases of hydrophilic polymer embolism (HPE) identified on brain tumor resection following Wada testing. One patient experienced multifocal vascular complications and diffuse cerebral edema, while the other had an uneventful postoperative course. Wada testing is frequently performed during preoperative planning prior to epilepsy surgery or the resection of tumors in eloquent brain regions. These cases demonstrate the need for increased recognition of this histologic finding to enable further correlation with clinical outcomes.
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Primary age-related tauopathy (PART) is a neurodegenerative entity defined as Alzheimer-type neurofibrillary degeneration primarily affecting the medial temporal lobe with minimal to absent amyloid-ß (Aß) plaque deposition. The extent to which PART can be differentiated pathoanatomically from Alzheimer disease (AD) is unclear. Here, we examined the regional distribution of tau pathology in a large cohort of postmortem brains (n = 914). We found an early vulnerability of the CA2 subregion of the hippocampus to neurofibrillary degeneration in PART, and semiquantitative assessment of neurofibrillary degeneration in CA2 was significantly greater than in CA1 in PART. In contrast, subjects harboring intermediate-to-high AD neuropathologic change (ADNC) displayed relative sparing of CA2 until later stages of their disease course. In addition, the CA2/CA1 ratio of neurofibrillary degeneration in PART was significantly higher than in subjects with intermediate-to-high ADNC burden. Furthermore, the distribution of tau pathology in PART diverges from the Braak NFT staging system and Braak stage does not correlate with cognitive function in PART as it does in individuals with intermediate-to-high ADNC. These findings highlight the need for a better understanding of the contribution of PART to cognitive impairment and how neurofibrillary degeneration interacts with Aß pathology in AD and PART.
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Envejecimiento/patología , Región CA2 Hipocampal/patología , Neuronas/patología , Tauopatías/patología , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Péptidos beta-Amiloides/metabolismo , Región CA2 Hipocampal/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ovillos Neurofibrilares/metabolismo , Ovillos Neurofibrilares/patología , Neuronas/metabolismo , Placa Amiloide/metabolismo , Placa Amiloide/patología , Tauopatías/metabolismo , Proteínas tau/metabolismoRESUMEN
OBJECTIVE: To examine whether domain-specific patterns of cognitive impairment and trajectories of decline differed in patients with clinically diagnosed Parkinson disease dementia (PDD) (N = 29) and autopsy-confirmed dementia with Lewy bodies (DLB) (N = 58) or Alzheimer disease (AD) (N = 174) and to determine the impact of pooling patients with PDD and DLB in clinical trials targeting cognition. METHODS: Patients were matched on demographics and level of global cognitive impairment. Patterns of cross-sectional performance and longitudinal decline were examined in 4 cognitive domains: Visuospatial, Memory, Executive, and Language. Power analyses were performed to determine the numbers of participants needed to adequately power a hypothetical clinical trial to slow cognitive decline in pure PDD, pure DLB, or a mixed PDD/DLB group. RESULTS: Both DLB and PDD were more impaired and declined more rapidly than AD in the Visuospatial domain. Patients with PDD exhibited the most impairment and fastest decline in Executive, although patients with DLB also declined faster than AD. Memory was more impaired in AD than DLB and in both compared with PDD; however, all 3 groups declined at comparable rates. In contrast, PDD declined at a slower rate on Language measures than DLB or AD. Power analyses suggest that Visuospatial and Executive outcome measures would be most sensitive in PDD, but Memory and Language in DLB. CONCLUSION: DLB and PDD differ from each other, and from AD, in a cognitive domain-specific manner. As such, different outcome measures may be most sensitive to detecting changes in DLB vs PDD, suggesting that the 2 should be analyzed separately in clinical trials.
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Cognición/fisiología , Demencia/fisiopatología , Enfermedad por Cuerpos de Lewy/fisiopatología , Enfermedad de Parkinson/fisiopatología , Anciano , Enfermedad de Alzheimer/fisiopatología , Estudios Transversales , Demencia/diagnóstico , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Memoria/fisiología , Pruebas NeuropsicológicasRESUMEN
This study aimed to determine if patterns of neuropsychological deficits, vascular risk factors, and neuropathology differ in Hispanic and Non-Hispanic patients with autopsy-confirmed Alzheimer's disease (AD). Participants were enrolled in a longitudinal study at the Shiley-Marcos AD Research Center at the University of California, San Diego. Hispanic (nâ=â14) and Non-Hispanic (nâ=â20) patients with autopsy-confirmed AD who scored ≥95 on the Dementia Rating Scale (DRS) were included. Patient groups were matched on age, education, global mental status, and severity of functional decline; they were compared to Hispanic (nâ=â14) or Non-Hispanic (nâ=â20) cognitively-normal controls of similar age and education. Ethnicity (Hispanic, Non-Hispanic) by disease state (autopsy-confirmed AD or cognitively normal) comparisons were made for cognitive test performance and vascular risk factors. Patient groups were further compared on measures of AD (Braak stage, neuritic plaques, neurofibrillary tangles), vascular neuropathology, and performance across cognitive domains of memory, language, attention, executive functions, and visuospatial abilities after scores were z-transformed based on respective culturally-appropriate control groups. Patient groups had similar overall AD pathology burden, whereas Hispanics with AD had more small parenchymal arteriolar disease and amyloid angiopathy than Non-Hispanics with AD. Despite largely similar pathology, Hispanics with AD were less cognitively impaired (relative to respective NC groups) than Non-Hispanics with AD, and exhibited a different pattern of deficits across cognitive domains. Findings suggest that cognitive deficits that are usually prominent in AD may be less salient in Hispanic patients and this may adversely impact the ability to clinically detect the disease in mild to moderate stages.
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Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Hispánicos o Latinos/estadística & datos numéricos , Enfermedades Vasculares/patología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Autopsia , Angiopatía Amiloide Cerebral/patología , Costo de Enfermedad , Etnicidad , Femenino , Humanos , Estudios Longitudinales , Masculino , Multilingüismo , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Enfermedades Vasculares/complicacionesRESUMEN
Hippocampal sclerosis (HS) is a prevalent cause of dementia in the oldest old but is generally misdiagnosed as Alzheimer's disease (AD) due to similarities in clinical presentation. To determine if clinical and cognitive features diverge over time, we compared results from longitudinal evaluations of participants in the University of California, San Diego, Alzheimer's Disease Research Center with autopsy-confirmed AD (n = 195), HS (n = 21), or both HS + AD (n = 18). Each group exhibited decline in all cognitive measures, with HS declining at a slower rate than AD on the Mini-Mental State Examination, immediate recall condition of a word-list learning test, and Dementia Rating Scale total and subtest scores (except memory). Five years before the final evaluation, more prominent semantic and visuospatial deficits were apparent in AD participants than in HS participants despite comparable global cognitive impairment. Groups did not differ on any measure of executive function. HS + AD differed from AD only on the Boston Naming Test. Overall, results suggest that HS dementia is associated with cognitive deficits that progress more slowly than, but generally mimic, those observed in AD.
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Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/patología , Hipocampo/patología , Anciano , Anciano de 80 o más Años , Autopsia , Disfunción Cognitiva/fisiopatología , Femenino , Humanos , Masculino , Memoria a Corto Plazo/fisiología , Enfermedades del Sistema Nervioso/patología , Enfermedades del Sistema Nervioso/psicologíaRESUMEN
Clinical, neuropsychological, and neurological procedures used to diagnose Alzheimer's disease (AD) and related dementias were largely developed and validated in well-educated, non-Latino, English-speaking populations. Sociocultural and genetic differences in Latinos might influence the accuracy of clinical diagnosis of AD and other dementias. We aim to compare the accuracy of the clinical diagnosis of AD and related dementias in Latinos with the corresponding neuropathological diagnosis. From the UCSD Alzheimer's Disease Research Center longitudinal cohort, we selected all Latino participants who had autopsy neuropathological studies from 1991 to 2017. Participants underwent annual neurological clinical evaluations, standard neuropsychological tests, neuroimaging, and genotyping of Apolipoprotein E. We calculated the sensitivity and specificity of the clinical diagnosis of AD against the primary pathological diagnosis. Of the 34 participants with a primary neuropathological diagnosis of AD, 33 (97.1%) were correctly clinically diagnosed as having AD at the last clinical evaluation, and 1 was incorrectly diagnosed with dementia with Lewy bodies. Of the 19 participants without a primary neuropathological diagnosis of AD, 8 were incorrectly clinically diagnosed with probable AD at the last clinic evaluation. The clinical diagnosis of AD at the last clinical evaluation had 97.1% sensitivity and 57.9% specificity for autopsy-verified AD. In this Latino cohort, clinicians predicted AD pathological findings with high sensitivity but moderate specificity. Tangle-only dementia was the most common misdiagnosis. Our study suggests that current procedures and instruments to clinically determine AD in Latinos have high sensitivity compared with neuropathology, but specificity needs to be improved.
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Enfermedad de Alzheimer/diagnóstico , Encéfalo/patología , Demencia/diagnóstico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Demencia/patología , Demencia/psicología , Dibenzocicloheptenos , Femenino , Hispánicos o Latinos , Humanos , Masculino , Pruebas Neuropsicológicas , Sensibilidad y EspecificidadRESUMEN
Despite considerable research to uncover them, the anatomic and neuropathologic correlates of memory impairment in dementia with Lewy bodies (DLB) remain unclear. While some studies have implicated Lewy bodies in the neocortex, others have pointed to α-synuclein pathology in the hippocampus. We systematically examined hippocampal Lewy pathology and its distribution in hippocampal subfields in 95 clinically and neuropathologically characterized human cases of DLB, finding that α-synuclein pathology was highest in two hippocampal-related subregions: the CA2 subfield and the entorhinal cortex (EC). While the EC had numerous classic somatic Lewy bodies, CA2 contained mainly Lewy neurites in presumed axon terminals, suggesting the involvement of the EC â CA2 circuitry in the pathogenesis of DLB symptoms. Clinicopathological correlations with measures of verbal and visual memory supported a role for EC Lewy pathology, but not CA2, in causing these memory deficits. Lewy pathology in CA1-the main output region for CA2-correlated best with results from memory testing despite a milder pathology. This result indicates that CA1 may be more functionally relevant than CA2 in the context of memory impairment in DLB. These correlations remained significant after controlling for several factors, including concurrent Alzheimer's pathology (neuritic plaques and neurofibrillary tangles) and the interval between time of testing and time of death. Our data suggest that although hippocampal Lewy pathology in DLB is predominant in CA2 and EC, memory performance correlates most strongly with CA1 burden.SIGNIFICANCE STATEMENT This study provides a detailed neuropathologic analysis of hippocampal Lewy pathology in human patients with autopsy-confirmed dementia with Lewy bodies. The approach-informed by regional molecular markers, concurrent Alzheimer's pathology analysis, and relevant clinical data-helps tease out the relative contribution of Lewy pathology to memory dysfunction in the disease. Levels of Lewy pathology were found to be highest in the hippocampal CA2 subregion and entorhinal cortex, implicating a potentially overlooked circuit in disease pathogenesis. However, correlation with memory performance was strongest with CA1. This unexpected finding suggests that Lewy pathology must reach a critical burden across hippocampal circuitry to contribute to memory dysfunction beyond that related to other factors, notably coexisting Alzheimer's disease tau pathology.
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Hipocampo/metabolismo , Enfermedad por Cuerpos de Lewy/complicaciones , Trastornos de la Memoria/etiología , Trastornos de la Memoria/patología , alfa-Sinucleína/metabolismo , Anciano , Anciano de 80 o más Años , Autopsia , Proteínas de Transporte de Catión/metabolismo , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Sinucleínas/metabolismoRESUMEN
When "common things are common," the discovery of a subdural hemorrhage in an adult is most likely to be due to trauma. When the subdural hemorrhage is associated with an intraparenchymal hematoma, statistically speaking, the subdural hemorrhage is likely the result of a hypertensive hemorrhage that has ruptured into the subdural space or trauma that resulted from a collapse to the ground following hypertensive intra-axial bleeding. However, "common things" do not always explain the source of a subdural hemorrhage or intraparenchymal hematoma. In this case, an adult woman presented to the hospital obtunded and was diagnosed with a subdural hemorrhage (with mass effect) and intraparenchymal hematoma as the result of a ruptured dural arteriovenous fistula/malformation. This case highlights an unusual source of intracranial bleeding that resulted in death.
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INTRODUCTION: The goal was to compare subgroups of dementia with Lewy Bodies (DLB) using neuropathological measures to differentiate 'pure' Lewy body (LB) dementia from 'mixed' DLB [co-occurring LB and Alzheimer's disease (AD) pathology] to facilitate diagnostic decision-making and future development of interventions based on predicted type(s) of neuropathology. Studies comparing these groups are rare relative to those differentiating 'pure' AD and all-cause DLB, and are limited by insufficient sample size, brief cognitive batteries, and/or absence of autopsy confirmation. To address these limitations, we assessed cognition and other features in a large, autopsy-confirmed DLB sample using an extensive neuropsychological battery. METHODS: Subjects from an AD research center autopsy series satisfying DLB pathology criteria were divided by an AD neuropathology index into DLB-LB (Braak stage 0-3) (n = 38) and DLB-AD (Braak stage 4-6) (n = 41) and compared on baseline variables from chart reviews and standardized measures. RESULTS: DLB-LB subjects were more impaired on visuospatial constructions, visual conceptual reasoning, and speed of processing, but less impaired on verbal memory and confrontation naming. All-type hallucinations occurred more frequently in DLB-LB, while delusions were common in both groups. Groups were similar in education and age at onset, and in baseline age, dementia severity, and functional capacity. CONCLUSION: Salient findings included greater impairment on visual tasks and speed of processing and more frequent reports of all-type hallucinations in DLB-LB compared to DLB-AD. Relatively intact confrontation naming in DLB-LB and no differences in reported delusions were of note. Identifying differences in phenotypic features can improve prediction of underlying neuropathology.
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Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Autopsia , Trastornos del Conocimiento/etiología , Enfermedad por Cuerpos de Lewy/patología , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/diagnóstico , Evaluación de la Discapacidad , Femenino , Alucinaciones/fisiopatología , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/terapia , Masculino , Neuropatología , Pruebas Neuropsicológicas , Fenotipo , Escalas de Valoración PsiquiátricaRESUMEN
OBJECTIVES: Prominent impairment of visuospatial processing is a feature of dementia with Lewy bodies (DLB), and diagnosis of this impairment may help clinically distinguish DLB from Alzheimer's disease (AD). The current study compared autopsy-confirmed DLB and AD patients on the Hooper Visual Organization Test (VOT), a test that requires perceptual and mental reorganization of parts of an object into an identifiable whole. The VOT may be particularly sensitive to DLB since it involves integration of visual information processed in separate dorsal and ventral visual "streams". METHODS: Demographically similar DLB (n=28), AD (n=115), and normal control (NC; n=85) participants were compared on the VOT and additional neuropsychological tests. Patient groups did not differ in dementia severity at time of VOT testing. High and Low AD-Braak stage DLB subgroups were compared to examine the influence of concomitant AD pathology on VOT performance. RESULTS: Both patient groups were impaired compared to NC participants. VOT scores of DLB patients were significantly lower than those of AD patients. The diagnostic sensitivity and specificity of the VOT for patients versus controls was good, but marginal for DLB versus AD. High-Braak and low-Braak DLB patients did not differ on the VOT, but High-Braak DLB performed worse than Low-Braak DLB on tests of episodic memory and language. CONCLUSIONS: Visual perceptual organization ability is more impaired in DLB than AD but not strongly diagnostic. The disproportionate severity of this visual perceptual deficit in DLB is not related to degree of concomitant AD pathology, which suggests that it might primarily reflect Lewy body pathology. (JINS, 2016, 22, 609-619).
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Enfermedad de Alzheimer/fisiopatología , Enfermedad por Cuerpos de Lewy/fisiopatología , Pruebas Neuropsicológicas/normas , Percepción Visual/fisiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Autopsia , Humanos , Enfermedad por Cuerpos de Lewy/diagnósticoRESUMEN
Fatal, allegedly inflicted pediatric head trauma remains a controversial topic in forensic pathology. Recommendations for systematic neuropathologic evaluation of the brains of supposedly injured infants and children usually include the assessment of long white matter tracts in search of axonopathy - specifically, diffuse axonal injury. The ability to recognize, document, and interpret injuries to axons has significant academic and medicolegal implications. For example, more than two decades of inconsistent nosology have resulted in confusion about the definition of diffuse axonal injury between various medical disciplines including radiology, neurosurgery, pediatrics, neuropathology, and forensic pathology. Furthermore, in the pediatric setting, acceptance that "pure" shaking can cause axonal shearing in infants and young children is not widespread. Additionally, controversy abounds whether or not axonal trauma can be identified within regions of white matter ischemia - a debate with very significant implications. Immunohistochemistry is often used not only to document axonal injury, but also to estimate the time since injury. As a result, the estimated post-injury interval may then be used by law enforcement officers and prosecutors to narrow "exclusive opportunity" and thus, identify potential suspects. Fundamental to these highly complicated and controversial topics is a philosophical understanding of the diffuse axonal injury spectrum disorders.
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OBJECTIVE: Visual processing abilities of patients with dementia with Lewy bodies (DLB) or Alzheimer disease (AD) dementia were assessed psychophysically using a simple horizontal motion discrimination task that engages the dorsal visual processing stream. METHODS: Participants included patients with mild dementia with DLB, AD dementia or Parkinson disease (PD) with dementia (PDD), without dementia with PD, and normal controls. Participants indicated the left or right direction of coherently moving dots that were embedded within dynamic visual noise provided by randomly moving dots. The proportion of coherently moving dots was increased or decreased across trials to determine a threshold at which participants could correctly indicate their direction with greater than 80% accuracy. RESULTS: Motion discrimination thresholds of patients with DLB and PDD were comparable and significantly higher (i.e., worse) than those of patients with AD dementia. The thresholds of patients with AD dementia and patients with PD were normal. These results were confirmed in subgroups of patients with DLB/PDD and AD dementia with autopsy-confirmed disease. A motion discrimination threshold greater than 0.23 distinguished between DLB/PDD and AD dementia with 67% sensitivity and 85% specificity. CONCLUSIONS: Differential deficits in detecting direction of simple horizontal motion suggest that dorsal processing stream dysfunction is greater in DLB and PDD than in AD dementia. Therefore, impaired performance on simple visual motion discrimination tasks that specifically engage occipitoparietal brain regions suggests the presence of Lewy body pathology.
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Enfermedad de Alzheimer/diagnóstico , Aprendizaje Discriminativo , Enfermedad por Cuerpos de Lewy/diagnóstico , Percepción de Movimiento , Pruebas Neuropsicológicas , Estimulación Luminosa/métodos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Aprendizaje Discriminativo/fisiología , Femenino , Humanos , Enfermedad por Cuerpos de Lewy/fisiopatología , Enfermedad por Cuerpos de Lewy/psicología , Masculino , Percepción de Movimiento/fisiologíaRESUMEN
A 50-year-old male immigrant from Ethiopia presented for consultation after 3 years of hematochezia/melena requiring > 25 units of blood transfusions. Physical examination revealed severe proximal muscle wasting and weakness, central obesity, proptosis, and abdominal striae, accompanied by eosinophilia, elevated hemoglobin A1c, elevated 24-hour urinary cortisol, lack of suppression of 8 am cortisol levels by 1 mg dexamethasone, and inappropriately elevated random adrenocorticotropic hormone (ACTH) level. Histopathological examination of gastrointestinal biopsies showed large numbers of Strongyloides stercoralis, indicating Strongyloides hyperinfection. Treatment with 2 days of ivermectin led to resolution of gastrointestinal bleeding. This syndrome was due to chronic immunosuppression from a pituitary ACTH (corticotroph) microadenoma, of which resection led to gradual normalization of urine cortisol, improved glycemic control, resolution of eosinophilia, and no recurrence of infection.
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Hemorragia Gastrointestinal/etiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Strongyloides stercoralis , Estrongiloidiasis/diagnóstico , Enfermedad Aguda , Animales , Antihelmínticos/uso terapéutico , Hemorragia Gastrointestinal/parasitología , Humanos , Huésped Inmunocomprometido/inmunología , Ivermectina/uso terapéutico , Masculino , Persona de Mediana Edad , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/complicaciones , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/inmunología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/parasitología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/patología , Adenohipófisis/patología , Estrongiloidiasis/complicacionesRESUMEN
Evidence from patients with amnesia suggests that recognition memory span tasks engage both long-term memory (i.e., secondary memory) processes mediated by the diencephalic-medial temporal lobe memory system and working memory processes mediated by fronto-striatal systems. Thus, the recognition memory span task may be particularly effective for detecting memory deficits in disorders that disrupt both memory systems. The presence of unique pathology in fronto-striatal circuits in Dementia with Lewy Bodies (DLB) compared to AD suggests that performance on the recognition memory span task might be differentially affected in the two disorders even though they have quantitatively similar deficits in secondary memory. In the present study, patients with autopsy-confirmed DLB or AD, and Normal Control (NC) participants, were tested on separate recognition memory span tasks that required them to retain increasing amounts of verbal, spatial, or visual object (i.e., faces) information across trials. Results showed that recognition memory spans for verbal and spatial stimuli, but not face stimuli, were lower in patients with DLB than in those with AD, and more impaired relative to NC performance. This was despite similar deficits in the two patient groups on independent measures of secondary memory such as the total number of words recalled from long-term storage on the Buschke Selective Reminding Test. The disproportionate vulnerability of recognition memory span task performance in DLB compared to AD may be due to greater fronto-striatal involvement in DLB and a corresponding decrement in cooperative interaction between working memory and secondary memory processes. Assessment of recognition memory span may contribute to the ability to distinguish between DLB and AD relatively early in the course of disease.
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Enfermedad de Alzheimer/psicología , Enfermedad por Cuerpos de Lewy/psicología , Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Reconocimiento en Psicología/fisiología , Anciano , Enfermedad de Alzheimer/patología , Encéfalo/patología , Reconocimiento Facial/fisiología , Humanos , Enfermedad por Cuerpos de Lewy/patología , Escala del Estado Mental , Pruebas Neuropsicológicas , Percepción Espacial/fisiología , Percepción del Habla/fisiologíaRESUMEN
The differential diagnosis of spinal tumors is guided by anatomical location and imaging characteristics. Diagnosis of rare tumors is made challenging by abnormal features. The authors present the case of a 47-year-old woman who presented with progressive subacute right lower-extremity weakness and numbness of the right thigh. Physical examination further revealed an extensor response to plantar reflex on the right and hyporeflexia of the right Achilles and patellar reflexes. Magnetic resonance imaging of the lumbar spine demonstrated an 8-mm intramedullary exophytic nodule protruding into a hematoma within the conus medullaris. Spinal angiography was performed to rule out an arteriovenous malformation, and resection with hematoma evacuation was completed. Pathological examination of the resected mass demonstrated a spindle cell neoplasm with dense bundles of collagen. Special immunostaining was performed and a diagnosis of solitary fibrous tumor (SFT) was made. SFTs are mesenchymally derived pleural neoplasms, which rarely present at other locations of the body, but have been increasingly described to occur as primary neoplasms of the spine and CNS. The authors believe that this case is unique in its rare location at the level of the conus, and also that this is the first report of a hemorrhagic SFT in the spine. Therefore, with this report the authors add to the literature the fact that this variant of an increasingly understood but heterogeneous tumor can occur, and therefore should be considered in the differential of clinically similar tumors.
Asunto(s)
Hematoma/diagnóstico , Hematoma/cirugía , Tumores Fibrosos Solitarios/cirugía , Neoplasias de la Médula Espinal/diagnóstico , Neoplasias de la Médula Espinal/cirugía , Médula Espinal/patología , Biopsia , Diagnóstico Diferencial , Femenino , Hematoma/patología , Humanos , Laminectomía , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tumores Fibrosos Solitarios/diagnóstico , Tumores Fibrosos Solitarios/patología , Neoplasias de la Médula Espinal/patologíaRESUMEN
We examined the relationships of antemortem vascular risk factors to postmortem cerebrovascular and Alzheimer's disease (AD) pathologies. Eighty-four AD patients underwent an assessment of vascular risk (blood pressure, cholesterol, smoking, cardiovascular disease, diabetes, atrial fibrillation, transient ischemic attack [TIA], or stroke) and later underwent brain autopsy. Given our aim to examine mild cerebrovascular changes (CVCs), individuals were excluded if autopsy revealed large stroke. The most common forms of CVC were circle of Willis atherosclerosis followed by arteriosclerosis, lacunes, and microinfarcts. Excluding the history of TIA/clinical stroke, individual vascular risk factors were not associated with CVC. However, the presence of multiple vascular risk factors was associated with CVC. Furthermore, the presence of CVC was associated with lower Braak and Braak stage. These findings highlight the importance of aggregate risk in the vascular contribution to dementia. Interventions designed to maintain cerebrovascular health may represent important opportunities for preventing or delaying dementia, even when AD is the dominant pathology.