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Biomedical subjects

Bruce L Miller

Publications and source records attributed to Bruce L Miller.

At least 73 records · Page 4Linked to original sources
PubMed2003

Sporadic Creutzfeldt-Jakob disease mimicking variant Creutzfeldt-Jakob disease.

BACKGROUND: The determination of the form of prion disease and early diagnosis are important for prognostic, public health, and epidemiologic reasons. OBJECTIVE: To describe a patient with sporadic Creutzfeldt-Jakob disease (sCJD) who had a clinical history and initial electroencephalogram and magnetic resonance imaging findings consistent with variant CJD (vCJD). RESULTS: Results of a repeated electroencephalogram were suggestive of sCJD, and a subsequent brain biopsy confirmed this diagnosis. CONCLUSIONS: This case cautions against relying solely on T2- and diffusion-weighted pulvinar hyperintensity and clinical features to differentiate between vCJD and sCJD, and further supports established diagnostic criteria for vCJD.

Adult↗
PubMed2003

Challenging the clinical utility of the 14-3-3 protein for the diagnosis of sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative disorder for which there is no noninvasive and disease-specific test for premortem diagnosis. Previous studies have suggested that, in the proper clinical context, the 14-3-3 protein in cerebrospinal fluid is a reliable marker for sporadic CJD. OBJECTIVE: To assess the sensitivity of the cerebrospinal fluid 14-3-3 protein test among patients with definite sporadic CJD. DESIGN AND SETTING: We reviewed cases of sporadic CJD referred to our institution that were ultimately proved by pathological examination and on which cerebrospinal fluid 14-3-3 testing had been performed. PARTICIPANTS: Patients with CJD referred to our institution for clinical and/or pathological evaluation (biopsy- or autopsy-confirmed diagnosis) from January 1, 1998, through July 15, 2002, and on whom 14-3-3 testing had been performed. Thirty-two such patients with definite sporadic CJD were identified. Main Outcome Measure The 14-3-3 test results, from various laboratories, in these 32 patients. RESULTS: Seventeen of the 32 patients had a positive result for the 14-3-3 test, yielding a sensitivity of only 53%. A positive 14-3-3 result was significantly correlated with a shorter time between disease onset and the lumbar puncture for the 14-3-3 test. CONCLUSIONS: Testing for the 14-3-3 protein is only modestly sensitive to sporadic CJD, and we caution against ruling out a diagnosis of the disease on the basis of a negative 14-3-3 result.

14-3-3 Proteins↗
PubMed2003

Cinguloparietal atrophy distinguishes Alzheimer disease from semantic dementia.

BACKGROUND: Progressive brain atrophy is associated with Alzheimer disease (AD) and other dementias. Regional differences in brain atrophy may reflect clinical features of disease. OBJECTIVE: To identify regions of cerebral atrophy that are associated with AD vs other dementias. SETTING: University hospital dementia clinic. PARTICIPANTS: Eleven patients with AD and 11 with semantic dementia (SD), matched for age, sex, education, and degree of overall cognitive impairment and 15 normal controls. METHODS: Voxel-based morphometry was used to compare patterns of gray matter loss, measured on T1-weighted magnetic resonance images, between patients with AD or SD, a subtype of frontotemporal lobar degeneration, and controls. Statistically significant differences in regional gray matter concentration, after multiple-comparisons correction, between groups of subjects were identified. RESULTS: Patients with AD were more impaired than those with SD on tests of visuospatial function and on simple calculations. Consistent with these neuropsychological deficits, the most significant area of atrophy in the AD group was the left parietal cortex vs controls (z = 5.0; P =.04). Compared with SD, AD was associated with more atrophy in the left parietal lobe (z = 5.6; P =.04) and bilaterally in the posterior cingulate/precuneus (z = 5.1; P =.04). A discriminant function analysis demonstrated that the degree of atrophy of right posterior cingulate, left parietal lobe, right amygdala, and right anterior temporal lobe structures correctly classified 96% of the patients. CONCLUSION: Alzheimer disease is associated with a specific pattern of cortical atrophy compared with SD.

Aged↗
PubMed2003

Psychiatric and neuroimaging findings in Creutzfeldt-Jakob disease.

Although Creutzfeldt-Jakob disease (CJD) is the prototypical rapidly progressive dementia, clinical heterogeneity in the disease can make diagnosis difficult. Creutzfeldt-Jakob disease affects multiple brain areas, which causes multifocal deficits that involve movement, cognition, and psychiatric status. Thorough neurologic, cognitive, and psychiatric examinations are necessary for observing its clinical features. Recent advances in neuroimaging techniques have allowed researchers and clinicians to discover imaging patterns that distinguish CJD from other neurologic diseases. This article discusses how these advances may make neuroimaging the most valuable noninvasive tool for diagnosing CJD, which helps to track the progression of the disease course and provides insight into clinical-anatomic correlations.

Creutzfeldt-Jakob Syndrome↗
PubMed2003

Relationship between positive and negative symptoms and neuropsychological scores in frontotemporal dementia and Alzheimer's disease.

Patients with dementia, particularly those with frontotemporal dementia (FTD), are reported to display marked negative symptoms, including apathy, lack of initiative, and flattened affect, similar to those observed in schizophrenic patients. However, negative symptoms have yet to be formally quantified in an FTD population. Twenty-seven patients with FTD (11 primarily right-sided, 8 primarily left-sided, and 4 symmetric) and 7 patients with Alzheimer's disease were rated on the Scale for the Assessment of Negative Symptoms, the Positive and Negative Syndrome Scale, and the Emotional Blunting scale. The FTD patients registered significantly more negative symptoms than the Alzheimer's patients, averaging a threefold increase; groups did not significantly differ in positive symptoms. Negative symptom scale scores were negatively correlated with nonverbal executive skills (23-44% shared variance), verbal executive skills (up to 25% shared variance) and verbal memory (up to 20% shared variance), but were unrelated to measures of attention, verbal and nonverbal information processing, nonverbal memory, language, and constructional skill. In contrast, positive symptoms were positively correlated with constructional skill (19% shared variance) and attentional scores (15% shared variance). These findings add to the existing literature relating negative symptoms to anterior cerebral hypofunction, and suggest that positive symptoms, at least in this population, may be tied to increased posterior activation.

Aged↗
PubMed2003

Distinctive neuropsychological patterns in frontotemporal dementia, semantic dementia, and Alzheimer disease.

OBJECTIVE: To assess the ability of a brief neuropsychological bedside screening battery to discriminate between Alzheimer disease, frontotemporal dementia, and semantic dementia. METHODS: Subjects were 21 patients with frontotemporal dementia, 14 patients with semantic dementia, and 30 patients with Alzheimer disease comparable in terms of Mini Mental Status Examination score, age, and education. Frontotemporal dementia and semantic dementia diagnoses were made clinically using the consensus criteria of Neary et al. 1 Subjects were administered a brief neuropsychological screening assessing episodic memory, working memory, executive function, naming, spatial ability, abstract reasoning, and calculations. RESULTS: Both the Alzheimer disease and semantic dementia groups were significantly impaired relative to the frontotemporal dementia group on verbal memory, whereas only the Alzheimer disease group was impaired on visual memory. Frontotemporal dementia patients performed significantly worse on backward digit span and made significantly more executive errors than Alzheimer disease and semantic dementia patients. Semantic dementia patients were more impaired than Alzheimer disease and frontotemporal dementia patients on confrontation naming. Discriminant function analyses identified the 5 most discriminating variables that correctly classified 89.2% of cases. CONCLUSIONS: Frontotemporal dementia, semantic dementia, and Alzheimer disease are associated with distinct neuropsychological profiles that classify these dementia syndromes with considerable success. The neuropsychological profiles highlight the distinctiveness between the 3 syndromes, are consistent with the known loci of neuropathology in these conditions, and can potentially serve as an adjunct to the current clinical criteria.

Aged↗
PubMed2002

Heritability of lobar brain volumes in twins supports genetic models of cerebral laterality and handedness.

Although the left and right human cerebral hemispheres differ both functionally and anatomically, little is known about the environmental or genetic factors that govern central nervous system asymmetry. Nevertheless, cerebral asymmetry is strongly correlated with handedness, and handedness does have a significant genetic component. To explore the relative contribution of environmental and genetic influences on cerebral asymmetry, we examined the volumes of left and right cerebral cortex in a large cohort of aging identical and fraternal twins and explored their relationship to handedness. Cerebral lobar volumes had a major genetic component, indicating that genes play a large role in changes in brain volume that occur with aging. Shared environment, which likely represents in utero events, had about twice the effect on the left hemisphere as on the right, consistent with less genetic control over the left hemisphere. To test the major genetic models of handedness and cerebral asymmetry, twin pairs were divided into those with two right handers and those with at least one left hander (nonright handers). Genetic factors contributed twice the influence to left and right cerebral hemispheric volumes in right-handed twin pairs, suggesting a large decrement in genetic control of cerebral volumes in the nonright-handed twin pairs. This loss of genetic determination of the left and right cerebral hemispheres in the nonright-handed twin pairs is consistent with models postulating a right-hand/left-hemisphere-biasing genetic influence, a "right-shift" genotype that is lost in nonright handers, resulting in decreased cerebral asymmetry.

Aged↗
PubMed2002

Sporadic Pick's disease: a tauopathy characterized by a spectrum of pathological tau isoforms in gray and white matter.

Pick's disease is characterized neuropathologically by distinct tau-immunoreactive intraneuronal inclusions known as Pick bodies and by insoluble tau proteins with predominantly three microtubule-binding repeat tau isoforms. However, recent immunohistochemical studies showed that the antibody specific for exon 10, which encodes the fourth microtubule-binding repeat, detected other tau lesions in Pick's disease. To better define the spectrum of tau pathology in Pick's disease, we used biochemical, immunohistochemical, and ultrastructural techniques to analyze the tau isoform composition in 14 Pick's disease brains. Western blot analysis showed that both three and four microtubule-binding repeat pathological tau isoforms are present in gray and white matter of various brain regions. Using phosphorylation-dependent anti-tau antibodies, we show that major tau phosphoepitopes are present in sarcosyl-insoluble gray and white matter regions of Pick's disease brains. Also, for the first time to our knowledge, we demonstrated that isoforms with four microtubule-binding repeat tau isoforms are present in Pick bodies from selected brains. Isolated tau filaments were straight or twisted and formed by three microtubule-binding repeat or four microtubule-binding repeat tau isoforms. Major tau phosphorylation-dependent and exon 10-specific epitopes were present in filaments. Therefore, Pick's disease is characterized by an accumulations of Pick bodies in the hippocampal region and cortex as well as the presence of three and four microtubule-binding repeat tau pathology in both cortical gray and white matter that distinguish this tauopathy from other neurodegenerative disorders.

Aged↗
PubMed2002

Very early-onset familial Alzheimer's disease: a novel presenilin 1 mutation.

BACKGROUND: Early-onset familial Alzheimer's disease (EOFAD) is linked to mutations in three autosomal dominant genes: PS1, PS2 and APP. The clinical presentation and age of onset of mutations is variable. OBJECTIVES: The aim of this report is to describe a novel PS1 mutation believed to be causal for a very early onset of AD. METHODS: This is a case history using information from medical records, relative interviews and genetic testing results to describe the pre-clinical prodrome and clinical course of a patient with EOFAD. RESULTS: A previously undescribed G206V mutation in PS1 was found in the proband. CONCLUSION: The G206V mutation in PS1 is probably causal of a case of EOFAD with significant premorbid features.

Adult↗
PubMed2002

Emotion comprehension in the temporal variant of frontotemporal dementia.

Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by behavioural disorders that suggest abnormalities of emotional processing. Patients with the temporal variant of FTD (tvFTD) are particularly at risk for developing deficits in emotional processing secondary to atrophy in the amygdala, anterior temporal cortex (ATC) and orbital frontal cortex (OFC), structures that are components of the brain's emotional processing systems. In addition, previous studies have suggested that predominantly right, as opposed to left temporal atrophy is more likely to be associated with behavioural and emotional impairments in tvFTD. However, emotional processing has never been assessed directly in this group. We examined one aspect of emotional processing, namely the comprehension of facial expressions of emotion (emotional comprehension) in nine individuals with tvFTD, and correlated performance on this measure with atrophy (as measured from T(1)-weighted MRI scans by region of interest analysis) in the amygdala, ATC and OFC. Compared with age-matched controls, the tvFTD group was impaired in emotional comprehension, with more severe impairment for emotions with negative valence, including sadness, anger and fear, than for happiness. Emotional comprehension was correlated with atrophy in the right amygdala and the right OFC, and not with atrophy in other structures. When individual profiles of amygdala atrophy were examined across patients and compared with control values, right amygdala atrophy was always accompanied by left amygdala atrophy, whereas patients with volume loss in the left amygdala could have normal or decreased right amygdala volumes. Thus, emotional comprehension appeared to be most impaired when bilateral amygdala atrophy was present, and was not associated with the degree of left amygdala atrophy. Our data indicate that tvFTD is associated with impairments in emotional processing that may underlie some behavioural problems in this disorder, and that the emergence of such deficits depends on the specific pattern of anatomical injury. These results have implications both for the clinical presentation in tvFTD patients and for the study of the neuroanatomical basis of emotion.

Aged↗
PubMed2002

Recollection-based memory in frontotemporal dementia: implications for theories of long-term memory.

It has been convincingly demonstrated that patients with semantic dementia (the temporal variant of frontotemporal dementia) can show intact recognition memory for pictorial stimuli. As yet, the contribution made by recollective processes to this ability and the status of associated neural regions have not been investigated in the disease. Here, we used both a source monitoring paradigm and an associative memory test to evaluate the ability of patients with semantic dementia to use recollection-based memory processes, and a volumetric MRI technique to assess the extent of atrophy in the hippocampus. Although some patients showed impaired source and associative memory, many performed as well as control participants. Importantly, status of semantic knowledge, as measured by tests of comprehension and production, did not predict recollection-based memory ability. There was no significant positive correlation between recollection and volume of the hippocampus; instead, both source discrimination and associative memory correlated highly with performance on a battery of frontal lobe tests. Consistent with the view that damage to the prefrontal cortex might influence recollection performance, patients with the frontal variant of frontotemporal dementia, with atrophy largely confined to the frontal lobes, all performed at floor level on source discrimination. These results provide further compelling evidence in favour of the multiple input model of long-term memory and highlight the role of frontal lobe systems in recollection-based memory.

Aged↗
PubMed2002

Frontotemporal dementia classification and neuropsychiatry.

BACKGROUND: Frontotemporal dementia (FTD) is a syndrome encompassing the clinical expression of frontal or temporal lobe degeneration. The many clinical phenotypes of FTD include primary progressive aphasias and a more common frontotemporal degeneration with less marked language alteration but significant behavioral changes. SUMMARY: This paper describes the clinical progression of neuropsychiatric symptoms among 62 predominantly behavioral presentations and 30 language presentations of FTD. Disinhibition and depression became common for both subject groups over the course of illness. Significantly more cases presenting with behavioral changes had apathy and disinhibition. CONCLUSIONS: Language presentations of FTD had longer latency to onset of distinct neuropsychiatric changes but eventually converge with the phenotype initially affected with behavioral change. Clinicians should anticipate such neuropsychiatric changes, prepare families for the course of illness in patients with either clinical presentation,treat symptomatically with psychotropic medications to help families cope with behaviorally disturbed patients.

Journal Article↗