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H R Brashear

Publications and source records attributed to H R Brashear.

At least 19 recordsLinked to original sources

Antibody types and IgG subclasses in paraneoplastic neurological syndromes.

Three major patterns of antineuronal antibody response have been identified in patients with paraneoplastic neurological syndromes: Type I ('Anti-Yo'), associated with cerebellar degeneration in the setting of breast or gynecological cancer, Type IIa ('anti-Hu') associated with encephalomyeloneuritis in patients with small cell carcinoma of the lung, and Type IIb ('anti-Ri') associated with breast cancer. We have employed immunofluorescence methods to determine the antibody classes and the IgG subclasses which react with neurons in each of these patterns of paraneoplastic antibody response. In this study, IgG was the only antibody class identified; IgM and IgA antibodies were not found. IgG1 was the major subclass represented and was found in 9/9 patients with Type I antibody response, 26/27 patients with Type IIa antibody response, and 3/3 patients with Type IIb antibody response. Many patients also exhibited positive staining for IgG2 and IgG3. Trace amounts of IgG4 antineuronal antibodies were detected in a single patient with Type I antibody response; IgG4 antibodies were not found in other patients. Patients with paraneoplastic neurological syndromes exhibit an antibody response which is overwhelmingly IgG and is comprised predominantly of IgG subclasses capable of fixing complement. The role of these antibodies in the pathogenesis of paraneoplastic neurological disease remains uncertain.

Antibodies, Monoclonal↗

Neuropsychological assesment of psychogeriatric patients with limited education.

Traditional published norms for neuropsychological tests that do not consider demographic effects can lead to spuriously high false positive rates among low-educated elderly individuals. This problem may be compounded when trying to identify dementia in psychogeriatric patients whose cognitive functioning is also compromised by psychiatric illness. This study investigated the clinical utility of low education neuropsychological test norms to discriminate amongst demented and nondemented psychogeriatric inpatients and healthy community elderly with limited education. Results indicated that the Mattis Dementia Rating Scale (MDRS), the Fuld Object Memory Evaluation (FOME), the Mini-Mental State Examination (MMSE), and a Clock drawing task had high discriminability in differentiating the three groups. Application of demographically corrected norms has important implications for diagnosis and treatment planning, especially when neuropsychological status is complicated by psychiatric illness.

Aged↗

Patients with Alzheimer's disease who cannot perform some motor skills show normal learning of other motor skills.

Previous researchers have claimed that patients with Alzheimer's disease (AD) learn new motor skills normally, although many AD patients cannot perform the tasks and must be eliminated from the analysis. Excluding them assumes that they have a deficit of motor performance (competence to perform the task), but not of motor learning (ability to improve performance). The present study administered 4 motor tasks to 20 AD patients and 20 controls. The results showed that the ability to complete 1 task (performance) did not predict the rate of improvement (learning) on another task, which indicates that AD patients do indeed have a performance deficit and not a general deficit of motor skill learning. Dementia ratings predicted the ability to perform tasks but not the ability to learn them. It is concluded that it is defensible to claim that AD patients learn a motor skill normally, even if some of the patients are unable to perform the task.

Aged↗

Identification of autoantibody epitopes of glutamic acid decarboxylase in stiff-man syndrome patients.

Stiff-man syndrome is a neurologic disorder characterized by progressive rigidity of skeletal muscles. Deficiency of the neurotransmitter gamma-aminobutyric acid and autoantibodies to glutamic acid decarboxylase (GAD), the enzyme synthesizing gamma-aminobutyric acid, are closely associated with the disorder, although the relevant antigenic epitopes have not been identified. In the present study, sera from two patients with SMS was used in an immunoblotting assay with recombinant GAD67 (M(r) 67,000) and GAD65 (M(r) 65,000) isoforms to test whether SMS sera can recognize specific epitopes. We found that both SMS sera recognized the GAD65, but not the GAD67, isoform. Using 13 different synthetic GAD peptides to block the autoantibodies, two GAD65 epitopes were identified. One epitope recognized by both patients' sera, was blocked by the peptide representing amino acid residues 354-368. In one patient only, blocking was also observed by a peptide representing residues 390-402, which includes the binding site of the GAD cofactor, pyridoxal 5'-phosphate. A single amino acid substitution in GAD65 at position 401 (leucine to proline) and representing the analogous GAD67 sequence in this region significantly reduced the peptide's inhibitory effect. These findings suggest that SMS GAD autoantibodies share distinct GAD65 linear epitopes and that some SMS patients' autoantibodies may block the active site, explaining SMS GABA deficiency.

Adult↗

Cognitive screening of nursing home residents: factor structures of the Mini-Mental State Examination.

OBJECTIVE: To examine factor structures of the Mini-Mental State Examination, attempting first to replicate any of previously proposed 2-factor solutions; and to explore, secondly, the presence of clinically more differentiated and statistically stable factor structures representing common neurocognitive dimensions. DESIGN: Factor analytic investigation of descriptive dataset collected on nursing home residents. Two factor analyses were performed, one in which the number of factors was fixed at 2 in an effort to replicate previous studies, and one in which the number of factors to retain was determined by the scree test. Both factor analyses used established methods for judging the adequacy of the correlation matrix and the significance of factor loadings, and both applied principal components analysis for initial factor extraction and the equamax criterion for orthogonal rotation. SETTING: Seven nursing homes with a total of 894 beds. PARTICIPANTS: 922 assessments on nursing home residents were performed, of which 892 were complete and entered into the factor analyses. The observation-to-variable ratio exceeded 81:1, assuring the statistical stability of factor solutions derived. MEASUREMENT: The Mini-Mental State Examination, with standardization of words to be recalled and the inverted spelling of "world" as the mental reversal task. MAIN RESULTS: Two factor structures were derived. A 2-factor solution, explaining 36.5% of the variance and statistically and conceptually different from those obtained in previous studies, distinguished between Perceptual-Organizational and Psychomotor skills. A 4-factor solution, which explained 56.1% of the variance, included a factor named Executing Psychomotor Commands, while also further differentiating the perceptual-organizational processes into the factors of Memory, Concentration, and Language. CONCLUSION: The 2-factor solution shows that, notwithstanding previous claims to the contrary, the MMSE can make stable and independent distinctions between psychomotor and perceptual-organizational processes. However, this solution is statistically and conceptually limited and, therefore, of limited clinical and scientific relevance. The 4-factor solution of the MMSE maps well onto commonly recognized dimensions of neurocognitive ability. It offers a stable, intuitively sound, and statistically supported framework for clinical differentiation of cognitive screening data into independent clinical dimensions of neurocognitive functioning. Thus, it offers clinicians and researchers a 4-dimensional framework for interpreting data obtained by means of the MMSE. Studies with other populations of cognitively impaired and intact elderly are recommended to validate and extend the present findings.

Aged↗

Multidisciplinary assessment of patients with Alzheimer's disease.

The complexity of AD necessitates that multiple disciplines interface effectively in the assessment of patient, caregiver, and family. This multidisciplinary effort should not be focused on the mere exchange of data. As this article emphasized, just from the perspective of nursing, it is critical that the various disciplines involved know about the purpose, focus, and process of assessment approaches used by each in the convergent effort to comprehensively evaluate the disease and its possible changes, as well as its impact on function, cognition, behavior, and emotion. From this article, it should be apparent that effective multidisciplinary assessment is not exchange of data but rather purposive interchange of clinical information to achieve the clinical goals of assessment, diagnosis, explanation, intervention, prognosis, and evaluation.

Alzheimer Disease↗

Limbic encephalitis occurring in association with Alzheimer's disease.

Paraneoplastic limbic encephalitis is a rare cause of subacute dementia. A patient with limbic encephalitis and small-cell lung carcinoma is reported in whom the onset of subacute cognitive impairment was obscured by concurrent Alzheimer's disease. MRI revealed increased T2 signal in medial temporal lobes which corresponded to inflammatory pathology demonstrated at necropsy. High titres of antineuronal antibody (type II, anti-Hu) were present at death. Direct immunofluorescent staining of necropsy tissue revealed IgG bound to most remaining neurons in the temporal lobe. Antineuronal antibody screening and MRI are important in detecting limbic encephalitis.

Aged↗

Quantitative autoradiography of hemicholinium-3 binding sites in human amygdala.

We report the binding properties and subnuclear localization of [3H]hemicholinium-3 binding sites in human amygdala using quantitative autoradiography. Specific binding was saturable and high affinity (apparent Kd 2-11 nM). Binding was highest in the basolateral nucleus which receives dense cholinergic innervation from the basal forebrain. Binding closely approximated acetylcholinesterase reactivity. These data support [3H]hemicholinium-3 as a quantitative marker for cholinergic terminals in human brain.

Aged↗

Localization of antibody in the central nervous system of a patient with paraneoplastic encephalomyeloneuritis.

We report a patient with severe paraneoplastic encephalomyeloneuritis, occult small-cell carcinoma of the lung, and high titers of circulating antineuronal antibody who died shortly after developing limbic encephalitis. The antibody was of IgG class and reacted specifically with nuclei and cytoplasm of all neurons in the pattern typical for encephalomyelitis and subacute sensory neuropathy associated with small-cell carcinoma (type II, anti-Hu). At autopsy, perivascular inflammatory infiltrates were prominent. All samples of serum, CSF, and postmortem peritoneal and pleural fluid contained high titers of antibody. Direct immunofluorescence of frozen tissue revealed IgG bound to most remaining neurons in multiple brain regions in a pattern similar to indirect immunofluorescence of normal brain tissue. IgG was also bound to tumor. Attempts to elute antibody from tissue decreased background staining but did not remove neuronal immunofluorescence. These results indicate that antibody can access and bind specifically to neuronal antigens in the brain during the course of paraneoplastic disease.

Antibodies↗

Autoantibodies to GABAergic neurons and response to plasmapheresis in stiff-man syndrome.

Stiff-man syndrome is a rare disorder of unknown etiology in which progressive rigidity, spasms, and continuous motor unit activity may be due to dysfunction of GABAergic inhibition of alpha motor neurons. Some patients with this disorder have evidence of autoantibodies reactive with glutamic acid decarboxylase (GAD). We describe a patient with progressive stiff-man syndrome and high titers of GAD-like immunoreactivity in serum but not spinal fluid. Plasmapheresis resulted in lowered antibody titers, decreased exteroceptive reflex responses, reduced motor unit activity, and marked clinical improvement. Immunohistochemistry using patient serum and plasma produced specific labeling of human and experimental animal tissue consistent with GABAergic neurons and terminal fields. This antibody response was not present in samples from more than 200 other patients. These results provide additional evidence of an autoimmune mechanism for stiff-man syndrome and indicate plasmapheresis may be beneficial in some patients.

Adult↗

Massive florid reactive periostitis.

Florid reactive periostitis is a rare, benign process usually occurring in the small, tubular bones of the hands and feet. Typically the lesion occurs in an adolescent or young adult and presents as a small area of pain and erythema over the affected bone. Although the histologic features may suggest malignancy, there is usually little radiographic evidence to support such a diagnosis. In the following report an unusual example of this entity is described whose large size and relentless local progression led to initial diagnostic uncertainty and eventual aggressive management. This case suggests that a wide spectrum of radiologic and morphologic changes may be seen in this entity and that a seemingly unrelated genetic disease may alter the typical clinical course.

Adolescent↗

A psychogeriatric nursing assessment protocol for use in multidisciplinary practice.

The assessment of geriatric patients with psychiatric or neurobehavioral problems demands a multidisciplinary approach linking nursing, psychiatry, neurology, geriatrics, and internal medicine. While the medical disciplines have relatively well-established approaches to assessing psychogeriatric patients, nursing lacks a comprehensive assessment strategy that supports both nursing and multidisciplinary practice. This article describes the Psychogeriatric Nursing Assessment Protocol (Abraham, 1989) developed for use in a multidisciplinary geriatric neuropsychiatric outpatient clinic. The relationship of the protocol to psychiatric, neurological, geriatric, and medical assessments is discussed in an attempt to clarify the linkages of knowledge and care required for successful service delivery to geriatric patients with psychiatric or neurobehavioral problems, as well as to their families and formal and informal caregivers.

Activities of Daily Living↗

Deep cerebral venous thrombosis. Clinical, neuroradiological, and neuropsychological correlates.

Thrombosis of the deep cerebral venous system is usually fatal, and patients are frequently stuporous or comatose at presentation. This report describes serial radiological and neuropsychological observations in an 18-year-old woman who remained alert and survived this disorder. In association with diencephalic edema seen on computed tomographic scan, she demonstrated disorientation, abulia, attentional deficits, memory loss, and dyscalculia and had impaired IQ scores: the performance scores were worse than the verbal scores. Significant aphasia or sensory loss was absent. She recovered full intellectual capacity in the course of follow-up examinations, and the diencephalic edema seen on the computed tomographic scan resolved despite persistent thrombosis of the straight sinus demonstrable on follow-up digital angiography.

Adolescent↗