The Vascular Access Questionnaire: assessing patient-reported views of vascular access.

BACKGROUND: The use of central venous catheters for vascular access in hemodialysis (HD) patients is associated with an increased risk of complications compared to arteriovenous fistulas (AVF). Despite this, catheter use remains high and patient satisfaction may be an important driver of catheter use. METHODS: We developed the Vascular Access Questionnaire (VAQ) to measure patient-reported views of their vascular access. Chronic HD patients at two centers were asked to rate how bothered they were by 17 access-related problems. VAQ symptom scores were compared between patients using catheters and those using fistulas for vascular access. RESULTS: Two hundred and twenty-two patients were eligible for the study. Symptom score was not different between patients using catheters and those using fistulas (p=0.36). However, patients using fistulas were more likely to be at least moderately bothered by pain, bleeding, bruising, swelling, and the appearance of their access than patients using catheters. Elderly patients reported lower symptom scores with catheters than fistulas. CONCLUSIONS: Patients appear to be primarily concerned with the appearance of their access and cannulation-related complications, particularly the elderly. Better education about the risk of adverse events with catheters and the implementation of measures aimed at reducing cannulation-related complications may help to increase fistula rates and improve patient satisfaction with their vascular access.

Home care assistance and the utilization of peritoneal dialysis.

Peritoneal dialysis (PD) may be declining because the elderly often have barriers to self-care PD. The objective of this study was to determine whether the availability of home care increases utilization of PD. In 134 incident chronic dialysis patients (median age 73), 108 (81%) had at least one medical or social condition, which was a potential barrier to self-care PD. Eighty percent of patients living in regions where home care was available were considered eligible for PD compared to 65% in regions without home care (P=0.01, adjusted). Each barrier reduced the probability of being eligible for PD by 26% (odds ratio 0.74, per condition, P=0.02) adjusted for age, sex, predialysis care, in-patient start, and availability of home care. In regions with and without home care, 59 and 58% of eligible patients choose PD when they were offered it (P=NS). The utilization of PD in the incident end-stage renal disease (ESRD) population living in regions with and without home care was 47 and 37%, respectively (P=0.27). The mean rate of home care visits over the first year was 4.3 per week (maximum available was 14 per week). Of the 22 assisted patients, 15 required chronic support, five graduated to self-care, and two started with self-care but later required assistance. Adverse events were similar between assisted PD and traditional modalities. Barriers to self-care PD are very common in the elderly ESRD population but home care assistance significantly increases the number of patients who can be safely offered PD.

Clinical, neuropathological and genetic aspects of the tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome in which patients develop hamartomatous lesions in the nervous system and a host of other organs. While considerable experience has been gained in defining the clinical spectrum of TSC, a number of nosological questions remain. Neuropathological studies have continued to refine our knowledge of the nervous system abnormalities that characterize TSC. Molecular genetic studies have implicated two chromosomal regions in the genesis of TSC, one on chromosome 9q and the other on chromosome 16p. The chromosome 16p gene, designated TSC2, has been cloned, although its function remains speculative. The identification of the TSC1 gene on chromosome 9q, along with functional studies and mutational analyses of both TSC genes, will likely provide fascinating insights into the pathogenesis of TSC.

An improved approach to prepare human brains for research.

We describe two protocols for preparing human brains collected for research and diagnosis. In both protocols, one half brain is processed for research and the other for neuropathological evaluation. Clinical, neuropathological and tissue mRNA retention data are used for sample categorization. In protocol 1, coronal, whole hemisphere slices cut at standardized landmarks are frozen with a cooling device at -90 degrees C, which yields discrete anatomical structures. In selected instances, small blocks of brain are frozen at -160 degrees C in liquid nitrogen vapor. Cooling device or liquid nitrogen vapor frozen samples are suitable for in situ hybridization, protein blotting or immunohistochemistry. Morphological freezing artifacts are minimal. In protocol 2, one half brain is frozen en bloc on dry ice; this tissue is suitable for regional evaluation of gene expression or neurochemistry. Morphological freezing artifacts are severe. In both protocols, the other half brain is fixed in formalin prior to sectioning and diagnostic evaluation. The standardized selection of paraffin blocks from each brain allows precise diagnoses to be established, including identification of dangerous infectious processes; moreover, it makes it possible to produce a set of uniformly selected blocks and slides for comparative studies. These protocols lead to standardized tissue preparation for research and reduce variables impairing interpretation and comparison of data.

The nosology of Creutzfeldt-Jakob disease and conditions related to the accumulation of PrPCJD in the nervous system.

Although typical cases of Creutzfeldt-Jakob disease are readily recognized pathologically and clinically, variant forms often pose a diagnostic challenge. From the 1920's, when this disease was first characterized, until quite recently diagnosis relied heavily on morphologic changes. New advances in immunoassays and PrP gene analysis now provide important adjuncts in recognizing the spectrum of disorders of PrP metabolism associated with these transmissible encephalopathies.

Deep sylvian fissure meningioma without dural attachment in an adult: case report.

Meningiomas are thought to arise from arachnoid cap or meningothelial cells that not only cluster on the surface of pacchionian granulations but also can cover the arachnoid membrane in other locations. This frequent apposition to the dura mater probably accounts for the usual attachment of the neoplasm to this layer. We report a deep sylvian fissure meningioma without dural attachments in the right hemisphere of an adult patient. The patient initially presented with simple partial seizures. Magnetic resonance imaging revealed a contrast-enhancing circular mass in the superior aspect of the insular region, deep to the inferior parietal lobule. Surgical exploration confirmed the absence of dural attachments. Microscopically, the tumor was found to be a sparsely cellular meningioma with an extensive collagenous matrix. A survey of the literature reveals that the majority of cases of meningiomas without dural attachments occur either in children or below the tentorium. Extremely rare cases of supratentorial meningiomas without dural attachment have been described in adults. The uncommon locations of these tumors at sites distant from the dura mater is postulated to reflect the rare occurrence of arachnoidal cap cells in the Virchow-Robin spaces along the cerebral vasculature or in pial layers distant from the dura mater.

In situ polymerase chain reaction demonstration of JC virus in progressive multifocal leukoencephalopathy, including an index case.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that is caused by JC papovavirus. The virus can be demonstrated in brains with PML using a variety of techniques. In situ polymerase chain reaction (PCR) is a new method that combines the sensitivity of PCR with the histological localization of in situ hybridization. We here show that in situ PCR can detect JC virus in archival tissue sections of 3 cases of PML, including 1 of the original cases described in 1958 and 1 case that was fixed in formalin for 7 weeks. JC virus DNA was amplified directly on tissue and demonstrated in the characteristic enlarged oligodendrocytes and bizarre astrocytes. These data illustrate the utility of the in situ PCR technique in detecting JC virus in archival sections, including those fixed for prolonged periods, and provide a historical footnote to the original report of PML.

The development of neuropathology at the Massachusetts General Hospital and Harvard Medical School.

Few institutions have shaped neuropathology as a discipline as profoundly as Massachusetts General Hospital (MGH) and Harvard Medical School. Their fascination over many decades is due to a unique accumulation of excellent, intellectually stimulating neurologists with a sincere interest in the morphologic and pathogenetic basis of nervous system diseases. Their approach was strictly case oriented and clinico-pathological conferences were developed to the highest standard. In this review, the foundations of neuropathology in Boston are recounted.

Pathology of multiple sclerosis: some new developments.

This chapter reviews some of the current investigations regarding the neuropathology of multiple sclerosis (MS). To an increasing degree, immunocytochemical methods are being used to extend the recognition of cellular activities, particularly of the immune system, in the lesions and surrounding tissues. To some extent, these studies are associated with electron-microscope observations. The blood-brain barrier is the site of the first pathologic events, but it is still unclear as to what initially opens the barrier, or how. As regards the demyelinative process itself, the general impression now is that the primary target of the attack by the disease process is the myelin sheath, not its parent cell, the oligodendrocyte. Uncertainty still exists as to the status of oligodendrocytes in MS. Some, but not all, survive. Remyelination regularly occurs early in MS lesions, but it is ineffective. Many neuropathologic questions remain unanswered and require further research.

[Huntington disease: 7 cases with relatively preserved neostriatal islets]. / Maladie de Huntington: sept cas avec îlots néostriataux relativement préservés.

Seven cases of Huntington's disease (HD) showing unusual neostriatal findings are reported. In these patients, the neostriatum contained scattered islets of relatively intact parenchyma. We attempted to determine whether these cases might represent a clinico-pathological entity, and also sought to acquire a better understanding of the neostriatal degenerative changes in HD. Cell counts showed that the number of neurons in the islets was the same as in the normal neostriatum, but there was an increased number of astrocytes. The nature of these islets is poorly understood. Analysis of their topography and of the morphometric data indicates that they probably do not represent preserved striosomes. In HD patients with preserved neostriatal islets, the symptoms appear earlier, and the course of the disease is more rapid than in HD patients with the usual neostriatal lesions. The exceptional neuropathological phenotype of our seven HD cases probably indicates a different genotype.

Proliferative and degenerative changes in striatal spiny neurons in Huntington's disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry.

Dysmorphic alterations of dendritic arbors and spines in spiny striatal neurons were identified in section-Golgi impregnations of moderate and severe grades of Huntington's disease (HD). These alterations could be characterized as either proliferative or degenerative changes. Proliferative changes included prominent recurving of distal dendritic segments, short-segment branching along dendrites, and increased numbers and size of dendritic spines. Degenerative alterations consisted of truncated dendritic arborizations, occasional focal dendritic swellings, and marked spine loss. Proliferative changes were found primarily in moderate grades of HD, while degenerative changes were predominantly found in severe grades. Cytopathologic changes increased with neuropathologic severity. Similar morphologic alterations were observed in calbindin D28k (Calb) stained neurons in HD striatum. The immunoreactive intensity of Calb staining was increased in the distal dendrites of positive neurons in HD striatum. The present findings provide morphologic and quantitative evidence that confirms an early and marked involvement of spiny striatal neurons in HD and suggest that neuronal growth, rather than degeneration, may be the harbinger of cell death in this disorder.

Phosphorylated neurofilament epitopes in the achromasic neurons of corticonigral degeneration.

By employing monoclonal phosphorylated neurofilaments antibody, we studied the abnormally pale-staining neurons in 3 cases of corticonigral degeneration by the avidin-biotin immunoperoxidase method. For comparison, the central chromatolysis in anterior horn cells secondary to cervical spine fracture and "ballooned" neurons in a case of Pick's disease and a case of Alzheimer's disease were studied with similar procedure. Achromasic neurons in the case of corticonigral degeneration and ballooned neurons in Pick's disease and Alzheimer's disease showed positive immunostaining, while neurons with central chromatolysis secondary to axonal injury did not. Our observations show that the achromasic neurons in corticonigral degeneration contain phosphorylated neurofilaments which share common antigenic characteristics with ballooned neurons in Pick's disease and Alzheimer's disease. The absence of positive immunostaining in reactive central chromatolysis suggests that despite the similarities in appearance with the usual histopathologic stains this cytoplasmic change is pathogenetically different from that in the other neuronal disorders mentioned above.

Decreased neuronal and increased oligodendroglial densities in Huntington's disease caudate nucleus.

Decreased density of neurons was found throughout the head of the caudate nucleus in Huntington's disease (HD), with the most severe neuronal loss early in the disease in the medial region. The density of reactive astrocytes is inversely proportional to the neuronal loss. In cases of mild Huntington's disease which had no identifiable abnormality on conventional neuropathologic evaluation (grade 0), there is a reduction in neuron density without an accompanying reactive astrocytosis. The pattern for decrease in neurons and accompanying astrocytosis suggests that the earliest changes occur in the most medial portion of the head of the caudate nucleus and subsequently sweep laterally across the caudate nucleus to the internal capsule. An increased density of oligodendrocytes is observed in the head of the caudate nucleus for the lower grades (0, 1 and 2). The decreased neuronal and increased oligodendroglial densities may be of significance in understanding the pathogenesis of HD. These altered densities, observed in the absence of reactive astrocytosis, suggest that these changes may not represent recent effects of disease, but rather that HD gene expression may influence brain cell densities from early in the life of the gene carrier.

Secondary optic nerve tumors.

Secondary tumors of the optic nerve are more common than primary optic nerve tumors. The involvement of the optic nerve may arise from direct invasion from intraocular malignancies, from hematopoietic malignancy, from meningeal carcinomatosis, or from distant primary tumors. Orbital tumors rarely invade the optic nerve, and brain tumors involve it only in their late stages.

Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study.

To identify those factors associated with cerebral hemorrhage among brains with cerebral amyloid angiopathy (CAA), we undertook a comparative postmortem histopathological study of amyloid-containing vessels in the brains of patients with and without hemorrhage. Those without hemorrhage were represented by the following two groups: (1) elderly patients from a large general hospital (n = 66; age range, 75-107 years) and (2) patients with various neuropsychiatric disorders (n = 70; age range, 27-96 years). CAA was found in 45% of the first group and in 54% of the second group. The findings in these patients were compared with those in 17 brains in which both CAA and cerebral hemorrhage were present. We found that CAA was more severe in the brains with cerebral hemorrhage than in those without, and that fibrinoid necrosis was seen only in the brains with cerebral hemorrhage (12 of the 17 brains). Microaneurysms occurred only in the presence of severe, rather than moderate or mild, CAA. Serial sections in 2 brains of patients with cerebral hemorrhage showed fibrinoid necrosis, microaneurysms, and vascular rupture in close association with the hemorrhage. In 2 patients, hemorrhage was precipitated by trauma, and in 1, it was secondary to metastatic carcinoma. The features of brains from patients with CAA that are most consistently related to cerebral hemorrhage are (1) a severe degree of CAA and (2) the presence of fibrinoid necrosis, with or without microaneurysms.

Type-specific identification of herpes simplex and varicella-zoster virus antigen in autopsy tissues.

To identify antigens of herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV) in human tissue, polyclonal antisera and an immunoperoxidase method were used to examine formalin-fixed, paraffin-embedded tissues from autopsy cases and experimentally infected animals. These antisera readily distinguished between HSV and VZV antigen, with no evident cross-reactivity. Antiser ato HSV-1 and HSV-2 were more strongly reactive with antigen of the homologous virus than with that of heterologous virus. This difference in immunoreactivity was used to discriminate between HSV-1 and HSV-2 antigens in experimentally infected animal tissues containing HSV antigens of known type and, by extrapolation, to distinguish between these antigens in human autopsy tissues. Thus, with appropriate antisera and tissue controls, HSV-1, HSV-2, and VZV can be identified in paraffin sections.