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B J Crain

Publications and source records attributed to B J Crain.

At least 19 recordsLinked to original sources
PubMed1997

Arterial changes after thrombolysis and percutaneous transluminal angioplasty in vertebrobasilar thrombosis.

We present clinicopathologic findings in a patient treated with intraarterial thrombolysis and angioplasty for vertebrobasilar thrombosis. Autopsy revealed a marked inflammatory infiltrate within the vertebral artery at the site of catheter manipulation. This finding may have important implications for the use of interventional angiography in cerebrovascular disease.

Angioplasty, Balloon↗
PubMed1996

Microglia are not exclusively associated with plaque-rich regions of the dentate gyrus in Alzheimer's disease.

The functional significance of microglia found in neuritic plaques in Alzheimer's disease (AD) remains a source of controversy. In the present study, we explored the anatomic relationships between microglia and neuritic plaques in order to determine the potential role of microglia in plaque formation. We chose to study the molecular layer of the hippocampal dentate gyrus, a brain region where plaques have a strong tendency to line up parallel to the adjacent granule cell layer. We found that ferritin-labeled microglia were indeed most numerous in the same distinct band as plaques, but that microglia were relatively more common in the outer molecular layer. The distribution of microglia was more variable than that of plaques. Overall, microglial cell distribution was a relatively poor predictor of plaque distribution, particularly when cases were considered individually. Thus, there must be multiple triggers for microglial cell activation and accumulation in the AD brain, triggers which do not all necessarily lead to neuritic plaque formation.

Aged↗
PubMed1996

Peripheral nerve biopsies.

Nerve biopsies require special handling procedures that may not be familiar to many surgical pathologists. Most pathology laboratories handle fewer than 10 nerve biopsies per year, often referring them to specialized laboratories for evaluation. However, initial handling procedures may affect the ability of the reference laboratory to evaluate the specimen, and the remote location may impede communications and increase the time required for diagnostic evaluation. In a recent needs assessment questionnaire conducted by the College of American Pathologists, a need for understanding the handling of peripheral nerve biopsies was identified. Reference laboratories reported that clinical history and electrophysiologic data are very helpful, both in planning the handling of the biopsy and in interpreting the findings. Understanding the clinical differential diagnosis and the relationships between the differential diagnosis and the use of specialized studies often helps in the initial handling of peripheral nerve biopsies, whether evaluated locally or referred to a specialized laboratory. In this paper, we offer some general guidelines for handling nerve biopsies, including the rationale for the studies commonly used to evaluate them. With this background, decisions may be made about handling specimens that are specific for the clinical situation and allow for the highest diagnostic yield and fastest turnaround times.

Adolescent↗
PubMed1996

Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain.

Amyloid precursor-like protein-2 (APLP-2) belongs to a family of homologous amyloid precursor-like proteins. In the present study we report on the expression and distribution of APLP-2 in fetal and adult human brain and in brains of patients with Alzheimer's disease. We demonstrate that APLP-2 mRNAs encoding isoforms predicted to undergo post-translational modification by chondroitin sulfate glycosaminoglycans are elevated in fetal and aging brains relative to the brains of young adults. Immunocytochemical labeling with APLP-2-specific antibodies demonstrates APLP-2 immunoreactivity in cytoplasmic compartments in neurons and astrocytes, in large part overlapping the distribution of the amyloid precursor protein. In Alzheimer's disease brain, APLP-2 antibodies also label a subset of neuritic plaques. APLP-2 immunoreactivity is particularly conspicuous in large dystrophic neurites that also label with antibodies specific for APP and chromogranin A. In view of the age-dependent increase in levels of chondroitin sulfate glycosaminoglycan-modified forms of APLP-2 in aging brain and the accumulation of APLP-2 in dystrophic presynaptic elements, we suggest that APLP-2 may play roles in neuronal sprouting or in the aggregation, deposition, and/or persistence of beta-amyloid deposits.

Adult↗
PubMed1995

Argyrophilic plaque-like deposits in children.

We recently examined the brain from an 8-month-old infant with Down's syndrome and found argyrophilic plaque-like deposits throughout the neocortex and cerebellum. To ascertain the specificity of this observation, we examined 27 additional brains from the pediatric autopsy service, including 1 from another patient with Down's syndrome. To our surprise, similar argyrophilic deposits were found in 16 of these cases. The deposits were equally well stained by three different silver stains and had the same size, shape, and distribution in gray matter as the diffuse amyloid plaques commonly seen in adults. However these structures appeared to be amyloid negative. There were no obvious differences in the primary diagnoses amongst the group of patients with argyrophilic deposits and the group without them, and the origin, permanence, and functional significance of these plaque-like deposits are still unknown. Nonetheless, their recognition is important since they may represent subtle brain injury and since similar structures in adults might easily be misinterpreted as true diffuse amyloid plaques.

Adult↗
PubMed1995

Making the diagnosis of mixed and non-Alzheimer's dementias.

Community pathologists are often called on to perform autopsies to confirm clinical diagnoses of Alzheimer's disease, by far the most common cause of dementia. Diagnostic criteria have been provided by the Consortium to Establish a Registry for Alzheimer's Disease. Beyond pure and simple Alzheimer's disease, a significant proportion of dementia brains will feature Alzheimer's disease mixed with Lewy bodies, historically associated with idiopathic Parkinson's disease, or combined with various manifestations of cerebrovascular disease. Less commonly, the pathologist will encounter Lewy body disease alone, pure cerebrovascular disease, Pick's disease, progressive supranuclear palsy, Creutzfeldt-Jakob disease, or dementia lacking distinctive histopathology. This article is intended to reacquaint pathologists with these disorders and to provide a practical step-by-step approach to making the diagnosis of these mixed and non-Alzheimer's dementias.

Alzheimer Disease↗
PubMed1994

Ipsilateral subcortical atrophy associated with temporal lobectomy.

Stereologic methods for determining the volume of cerebral structures in vivo via magnetic resonance imaging have identified unilateral hippocampal atrophy among patients with complex partial epilepsy of temporal lobe origin. Metabolic imaging has also identified altered metabolism in temporal as well as extratemporal regions among these patients. As the temporal cortex and subcortical nuclei of the limbic system are reciprocally connected with striatal projection fields, we examined the putamen nuclei for evidence of associated extratemporal volume asymmetry in patients before and after temporal lobectomy. There was no evidence of preoperative putamen volume asymmetry, but a significant postoperative decrement in ipsilateral putamen volume was observed. The magnitude of postsurgical putamen volume asymmetry was correlated with the duration of time since resection. Progressive degeneration of extratemporal projections of the temporal lobe may occur in association with temporal lobectomy.

Adolescent↗
PubMed1994

Interlaboratory comparison of neuropathology assessments in Alzheimer's disease: a study of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)

Concerns about intercenter variation in methods and interpretation prompted CERAD investigators to examine standardization of the neuropathological assessment of Alzheimer's disease (AD). Contiguous frontal lobe sections derived from autopsy brains of eight patients clinically diagnosed as having probable AD and two cognitively normal individuals were distributed to 24 neuropathologists from 18 medical centers in the United States and Canada. Using their routine staining method(s), neuropathologists determined the rank order of severity of AD neuropathology in these cases, as well as semiquantitative and quantitative senile plaque and neurofibrillary tangle frequencies. Ranking of the ten cases revealed 75% inter-rater reliability among the 24 raters. Semiquantitative analyses showed reasonable inter-rater agreement, whereas quantitative measures yielded significant differences between raters for plaque and tangle counts (p < 0.0001). These differences reflected variation in stain sensitivity, staining technique (even when the same stain was used), and interpretation of the histological findings. Ratings on the cases with the highest proportions of diffuse plaques showed the greatest dependence upon stain sensitivity and variability in interpretation. This study indicates that greater attention to quality improvement is needed for the neuropathological evaluation of AD, particularly when pooling data in multicenter studies such as CERAD.

Aged↗
PubMed1994

Creutzfeldt-Jakob disease in a pregnant woman with an implanted dura mater graft.

A 28-year-old woman with prior neurosurgery involving the placement of a cadaveric dural graft developed a rapidly progressive neurodegenerative disorder with prominent cerebellar dysfunction that was proven at autopsy to be Creutzfeldt-Jakob disease. She represents the second American to develop Creutzfeldt-Jakob disease in association with a dural graft. The unusual features of the case include the patient's initial clinical presentation with cerebellar ataxia in the absence of dementia, the widespread presence of kuru-type amyloid plaques on a histological examination of the brain, the development of clinical symptoms during pregnancy, and the subsequent delivery of a child who remains healthy at the age of 3 years.

Adult↗
PubMed1994

Dendritic pathology of granule cells in Alzheimer's disease is unrelated to neuritic plaques.

Neuritic plaques are the histologic hallmark of Alzheimer's disease (AD); however, the extent to which they are injurious to neurons is unclear. In order to investigate this problem, we intracellularly filled human dentate granule cells with Lucifer yellow in a lightly fixed slice preparation and studied the relationships between their dendrites and neuritic plaques. After counterstaining for plaques and drawing the filled granule cell dendrites, we found that there were significant differences in the morphology of dendrites in control and AD cases; granule cell dendrites from Alzheimer's cases were generally shorter, branched less profusely, and had fewer spines than those from age matched controls. Surprisingly, when dendrites traveled into plaques, they still bore spines and their morphology was distinct from that of the amyloid-stained dystrophic neurites surrounding them. Furthermore, within AD cases we found no significant differences between dendrites that were located directly beneath or passing through plaques and those that were located in plaque-free regions. We conclude that granule cell dendrites are not an integral component of plaques within their dendritic fields and that neuritic plaques have no direct effect on granule cells in the dentate gyrus.

Aged↗
PubMed1993

Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.

Amyloid beta-peptide (A beta) deposition in senile plaques and cerebral vessels is a neuropathological feature of Alzheimer disease (AD). We examined the possibility that commonly observed variability in A beta deposition in late-onset AD might be related to apolipoprotein E genotype (APOE gene; the two most common alleles are 3 and 4), since APOE4 is a susceptibility gene for late-onset AD and apolipoprotein E interacts strongly with A beta in vitro. In an autopsy series of brains of late-onset AD patients, we found a strong association of APOE4 allele with increased vascular and plaque A beta deposits. Late-onset AD patients with one or two APOE4 alleles have a distinct neuropathological phenotype compared with patients homozygous for APOE3.

Aged↗
PubMed1993

Pulsatile versus nonpulsatile reperfusion improves cerebral blood flow after cardiac arrest.

Cardiopulmonary bypass using nonpulsatile flow (NF) is currently advocated for treating refractory cardiac arrest. Although the heart can be revived using cardiopulmonary bypass support, the brain must recover if such therapy is to be considered successful. Previous studies have demonstrated that pulsatile flow (PF) reperfusion can improve neurologic outcome compared with NF reperfusion after cardiac arrest. The purpose of this study was to assess cerebral perfusion and oxygen consumption during either PF or NF reperfusion after cardiac arrest. Dogs (n = 22) underwent a 15-minute cardiac arrest followed by 1 hour of either PF or NF reperfusion. Microsphere techniques were used to assess cerebral perfusion and oxygen consumption at 3, 15, and 60 minutes of reperfusion. Mean arteriovenous gradients and total brain flows were similar in both groups. However, cerebral oxygen consumption was significantly improved at 3 minutes of reperfusion with PF versus NF (1.8 +/- 0.3 versus 0.9 +/- 0.3 mL O2.dL-1.min-1, respectively; p < 0.05). These results were coincident with improved gray-to-white flow ratios at 3 minutes of PF versus NF reperfusion (5.2 +/- 1.0 versus 2.0 +/- 0.3, respectively; p < 0.05). There were no statistically significant differences in brain perfusion variables by 15 minutes of reperfusion. However, a relative hyperemia was exhibited at 15 minutes of NF versus PF reperfusion, which suggests nutrient flow was insufficient during early NF versus PF reperfusion. In conclusion, PF reperfusion can better restore cerebral blood flow and oxygen consumption than can NF reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

In vitro MR microscopy of the hippocampus in Alzheimer's disease.

We used MR microscopy at 7 tesla to identify the anatomy of the degenerating hippocampus in Alzheimer's disease (AD), which we then correlated with the histopathologic findings in the same specimens. The specimens studied were resected postmortem from 13 patients with confirmed AD and from nine age-matched controls. We imaged the specimens in the coronal plane using either three-dimensional Fourier encoding or single-slice Carr, Purcell, Meiboom, Gill (CPMG) spin echo sequences. On all specimens imaged with the CPMG pulse sequence, we calculated the T2 relaxation times for subfields within the hippocampus. Histologic sections were taken from each specimen and compared with the corresponding MR image. Using histologic boundaries, we quantified the number of neuritic plaques and neurofibrillary tangles in each hippocampal subfield. We measured the area, morphometric characteristics, and width of identifiable signal variant regions on each image and compared these measurements with the histopathologic findings. The mean cross-sectional area of the hippocampus in AD was decreased by 31% compared with the control group. This atrophy was highly correlated with tangle counts within the hippocampus, but not with plaque counts. The width of the gray matter in hippocampal area CA1, as identified by MR, correlated with the total area of the hippocampus. An age-related decrease in the size of a low-signal region that corresponds histologically to input projections comprising part of the perforant pathway was identified. Measurements of the T2 relaxation times of hippocampal subfields showed little regional variability and were not accurate indicators of disease presence or severity (p > 0.05).

Aged↗
PubMed1993

Temporal lobe hypometabolism on PET: predictor of seizure control after temporal lobectomy.

To investigate the relationship of temporal lobe hypometabolism demonstrated on PET to surgical outcome and underlying pathology, we reviewed 30 consecutive epilepsy patients who underwent interictal PET studies with 18F fluorodeoxyglucose before temporal lobectomy. Two interpreters blindly reviewed the PET studies and graded them for degree, extent, and location of temporal lobe hypometabolism. Pathologic analysis of en bloc resected tissue showed mesial temporal sclerosis (n = 22), astrocytoma (n = 2), and no pathologic diagnosis (n = 6). Outcome (24 to 40 months' follow-up) was rated as seizure-free (21 patients), significantly improved (five patients), and not significantly improved (four patients). Both the degree and extent of the temporal lobe hypometabolism demonstrated on PET were strongly associated with subsequent seizure control. Pathologic findings, however, did not correlate with degree of PET hypometabolism or subsequent outcome. These data demonstrate that in patients judged to have temporal lobe epilepsy, the presence of temporal lobe hypometabolism is associated with a positive outcome after ipsilateral temporal lobectomy.

Adolescent↗
PubMed1992

Evaluation of cerebral biopsies for the diagnosis of dementia.

To identify those patients most likely to benefit from a cerebral biopsy to diagnose dementia, we reviewed a series of 14 unselected biopsies performed during a 9-year period (1980 through 1989) at Duke University Medical Center, Durham, NC. Pathognomonic features allowed a definitive diagnosis in seven specimens. Nondiagnostic abnormalities but not diagnostic neuropathologic changes were seen in five additional specimens, and two specimens were normal. Creutzfeldt-Jakob disease was the most frequent diagnosis. One patient each was diagnosed as having Alzheimer's disease, diffuse Lewy body disease, adult-onset Niemann-Pick disease, and anaplastic astrocytoma. We conclude that a substantial proportion of patients presenting clinically with atypical dementia are likely to receive a definitive diagnosis from a cerebral biopsy. However, in those with coexisting hemiparesis, chorea, athetosis, or lower motor neuron signs, cerebral biopsies are less likely to be diagnostic.

Adult↗
PubMed1991

Regionally selective effects of NMDA receptor antagonists against ischemic brain damage in the gerbil.

This study compared the ability of three N-methyl-D-aspartate (NMDA) receptor antagonists to prevent neuronal degeneration in an animal model of global cerebral ischemia. The model employed is characterized by damage to the striatum, hippocampus, and neocortex. Antagonists were administered to gerbils either before or after a 5-min bilateral carotid occlusion. The intraischemic rectal temperature was either maintained at 36-37 degrees C or allowed to fall passively to 28-32 degrees C. Antagonists and doses tested were 1 and 10 mg/kg of MK-801 (pre- or postischemia), 30 mg/kg of CGS 19755 preischemia, four 25 mg/kg doses of CGS 19755 administered between 0.5 and 6.5 h postischemia, and 40 mg/kg of MDL 27,266 (pre- or postischemia). All three NMDA receptor antagonists exhibited some degree of neuroprotective activity when the carotid occlusion was performed under normothermic conditions. Most of the treatments with antagonist markedly reduced striatal damage. CA1 hippocampal and neocortical pyramidal cells were spared by only three of the treatments, however, and the extent of neuroprotection varied widely from case to case. Toxic doses of antagonist were required to protect CA1 pyramidal cells from ischemic damage. Ischemic damage to hippocampal areas CA2-CA3a and CA4 appeared to be resistant to all of these treatments. Most CA1 pyramidal cells that were protected from degeneration by an NMDA receptor antagonist were histologically abnormal. The neuroprotective effects of MK-801 and intraischemic hypothermia appeared to be additive. MK-801 (10 mg/kg) consistently reduced the postischemic brain temperature, but only the magnitude of hypothermia produced soon after reperfusion correlated with its neuroprotective action. These results suggest that NMDA receptor antagonists are relatively poor neuroprotective agents against a moderately severe ischemic insult.

Animals↗
PubMed1991

Pulsatile reperfusion after cardiac arrest improves neurologic outcome.

Cardiopulmonary bypass (CPB) using nonpulsatile flow (NPF) is advocated for refractory cardiac arrest. This study examined cerebral outcome after resuscitation with pulsatile flow (PF) versus NPF. Dogs arrested for 12.5 minute were reperfused with NPF (n = 11) using roller pump CPB or PF (n = 11) using mechanical biventricular cardiac massage. Pump flows were similar between groups; however early arterial pressures were greater during PF versus NPF, *p less than 0.05. Circulatory support was weaned at 60 minutes' reperfusion. Neurologic recovery of survivors (n = 16) was significantly better after PF versus NPF, *p = 0.01. The presence of brain lesions on magnetic resonance images did not significantly differ between groups at 7 days. Brain then were removed and regions examined for ischemic changes. Loss of CA1 pyramidal neurons was more severe after NPF versus PF, +p = 0.009. Ischemic changes were more frequent after NPF in the caudate nucleus (+p = 0.009) and watershed regions of the cerebral cortex (+p = 0.062), compared with PF. These results demonstrate that PF improves cerebral resuscitation when treating cardiac arrest with mechanical circulatory support (* = MANOVA with repeated measures, + = categorical data analysis.

Analysis of Variance↗