Back pain and paraplegia in a fifteen-year-old boy.
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Adolescent↗
Biomedical subjects
G N Fuller
Publications and source records attributed to G N Fuller.
Pseudoaxonal Guillain-Barré syndrome: severe demyelination mimicking axonopathy. A case with pupillary involvement.
A patient with fulminant Guillain-Barré syndrome developed pupillary denervation, loss of all brain stem reflexes and a complete flaccid quadriparesis. Pathological studies confirmed this was due to a primarily demyelinating process and not an axonal form of Guillain-Barré syndrome.
Brain↗
Cytomegalovirus and the peripheral nervous system in AIDS.
Cytomegalovirus (CMV) has been associated with a spectrum of peripheral nerve syndromes in patients with AIDS. Lumbosacral polyradiculopathy, a rapidly progressive syndrome occurring in about 1% of AIDS patients, is characterized by low back pain, sphincter disturbance, progressive flaccid paraparesis, and neutrophil cerebrospinal fluid pleocytosis. CMV has been found consistently in the lumbosacral roots in association with inflammation, demyelination, and axonal loss. Anti-CMV therapy has been reported in open studies to prolong survival and may lead to improvement of the neurologic deficit. A few patients with mononeuritis multiplex have been found to have CMV inclusions associated with inflammation and axonal loss in the peripheral nerve. The diagnosis, dependent on finding CMV in a biopsy sample, has been made too infrequently to estimate the incidence and prognosis or response to treatment. Painful distal symmetrical peripheral neuropathy, the most frequent neuropathy in AIDS, is characterized by subacute onset of pain in the feet, with associated findings including mild sensory signs and fiber degeneration axonal atrophy on sural nerve biopsy. A prospective study found an association of this syndrome with CMV disease of other organs, and CMV has been found in the dorsal root ganglion in a single case. Anti-CMV therapy might be of benefit in these peripheral nerve syndromes; however, the effect of such treatment needs to be assessed in controlled studies.
Acquired Immunodeficiency Syndrome↗
Other neurological diseases in HIV-1 infection: clinical aspects.
HIV-1-related neurological diseases, excluding opportunistic infections and HIV encephalitis, are considered here. Most occur in severely immunosuppressed patients, with CD4 counts of under 200 x 10(6) l-1. Primary brain lymphoma and metastases from systemic non-Hodgkin's lymphoma, the second commonest cause of cerebral mass lesions in AIDS, are usually aggressive B cell tumours. Their poor median survival after treatment, compared with that of lymphomas in non-AIDS patients, seems related to systemic complications, particularly opportunistic infections. Kaposi's sarcoma produces neurological symptoms exceptionally. Cerebral infarction is often unrecognized clinically but large vessel arteritic occlusions may occur. Intracranial haemorrhages occur mostly in thrombocytopenic patients. Seizures are frequently referred to the neurologist; investigation may lead to a diagnosis of AIDS. Nearly 50% of patients with seizures have cerebral toxoplasmosis or cryptococcal meningitis; HIV-1 encephalitis is presumed to be the cause in 30%. A subacute or chronic vacuolar myelopathy with pyramidal and posterior column signs is the commonest form of spinal cord involvement in AIDS; its cause remains unknown. Peripheral nerve syndromes occur at all stages of HIV-1 infection. Distal symmetrical peripheral neuropathies are the most frequent, particularly a painful form with axonal atrophy, associated with CMV infection, and seen during ARC or AIDS. Mononeuritis multiplex due to vasculitis, CMV, or lymphoma and a serious lumbosacral polyradiculopathy due to CMV are infrequent. The commonest myopathy is due to zidovudine (AZT); it usually responds to drug withdrawal. The nature, prognosis and optimal management of most other myopathies is yet to be determined.
AIDS Dementia Complex↗
The Prime Minister, Mrs Thatcher, and dementia.
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Aged↗
Osteoblastic metastases from astrocytomas: a report of two cases.
The spread of primary central nervous system (CNS) neoplasms beyond the confines of the neuraxis is a relatively uncommon observation. Extraneural metastases involving bone are quite rare, and have been observed almost exclusively in cases of medulloblastoma, high-grade (III-IV) astrocytoma, and glioblastoma multiforme. To date there has been only one case reported of bone metastasis from a "well-differentiated" astrocytoma. We now report two cases of astrocytoma in children with diffuse osteoblastic metastases and a fulminant clinical course. These cases demonstrate that due to the potential morphologic heterogeneity of these neoplasms, an initial biopsy diagnosis of low-grade astrocytoma does not always imply a benign clinical course.
Adolescent↗
Disialoganglioside GD2 in human neuroectodermal tumor cell lines and gliomas.
Monoclonal antibodies (mAbs) recognizing the disialoganglioside II3(NeuAc)2GgOse3Cer (GD2) were produced by immunizing mice with the GD2-expressing neuroblastoma cell line LAN-1 and a prefusion boost with purified GD2 coupled to Salmonella minnesota. Two IgM mAbs were isolated which demonstrated high levels of reactivity (binding ratios in excess of 100) with GD2 by solid-phase radioimmunoassay and positivity in high-performance thin-layer chromatography (HPTLC) immunostain; only one (DMAb-20) was subsequently shown by analysis with a panel of defined ganglioside species to be specific for the minimum epitope of GD2 GalNAc beta 1-4(NeuAc alpha 2-8-NeuAc alpha 2-3)Gal-, DMAb-20 was used to evaluate the expression of GD2 by malignant glioma and medulloblastoma cell lines using cell surface radioimmunoassay. indirect membrane immunofluorescence. HPTLC immunostain, and densitometric analysis of extracted gangliosides from selected cell lines. Sixteen of 20 (80%) malignant glioma and 5 of 5 medulloblastoma cell lines reacted with DMAb-20; in agreement with previous studies, 5 of 5 neuroblastoma and 2 of 3 melanoma cell lines also reacted with DMAb-20, GD2 was proportionally increased in the glioma and medulloblastoma cell lines relative to levels in normal brain, as determined by densitometric analysis. In a phenotypic survey of malignant glioma biopsies, tumor cells in 24 of 30 (80%) cases stained positively with DMAb-20. Reactive astrocytes, both within the adjacent to tumors, were frequently intensely stained. Among the morphological variants of glioblastoma examined, the most intense staining with DMAb-20 was observed in neoplastic gemistocytes, with the weakest or absent staining in small cell glioblastomas. As GD2 is a commonly expressed surface antigen of gliomas and medulloblastomas, expression of which is retained in tissue culture. DMAb-20 will be useful in determining the functional role of GD2 in cell-cell interaction, adhesion, and invasion, and in defining altered growth control mechanisms of central nervous system neoplasms in in vitro models.
Animals↗
Central nervous system involvement by cutaneous T cell lymphoma.
Central nervous system disease in cutaneous T cell lymphoma is uncommon and is usually not considered in standard therapeutic regimens. We report three patients who had cutaneous T cell lymphoma with involvement of the central nervous system and review the cases of 28 such patients reported in the literature. Potential risk factors, the reliability of various diagnostic tests, and potential therapeutic modalities are discussed.
Aged↗
Occurrence of lacto series gangliosides 3'-isoLM1 and 3',6'-isoLD1 in human gliomas in vitro and in vivo.
Monoclonal antibodies (MAb; DMAb, monoclonal antibodies derived at Duke Medical Center) directed against the oncofetally expressed lactotetraosyl gangliosides 3'-isoLM1 (IV3NeuAc-LcOse4Cer) and 3',6'-isoLD1 (IV3NeuAc,III6NeuAc-LcOse4Cer) were produced and their reactivity spectra compared to that of the alpha-3'-isoLM1 MAb SL-50. The IgM MAb SL-50 defines the epitope NeuAc (or NeuGc)alpha 2-3Gal beta 1-3GlcNAc, the terminal sequence of both gangliosides. SL-50 requires an unsubstituted GlcNAc residue; IgM DMAb-14 will accept the alpha 2-6 linked sialic acid to GlcNAc found in 3',6'-isoLD1. Immunohistochemical localization of 3'-isoLM1 was performed on 31 biopsy specimens of human gliomas; 15 (48%) expressed 3'-isoLM1 as defined by binding of MAb SL-50. Staining of small anaplastic cells, giant cells, and the glial component of gliosarcomas was observed. Neoplastic gemistocytes, when present, showed particularly intense staining. The 3'-isoLM1 and 3',6'-isoLD1 distribution in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Six of 29 cell lines expressed 3'-isoLM1: 2/16 gliomas, 3/3 teratomas, 1/1 pancreatic adenocarcinoma. No cell line expressed detectable 3',6'-isoLD1 by immunostain analysis of ganglioside extracts. The 3'-iso-LM1-positive cell lines expressed it in xenograft form; in five xenografts, the corresponding cell lines of which were 3'-isoLM1-negative, it was a proportion of the monosialoganglioside fraction. 3',6'-isoLD1 was detected in two xenografts, D-54 MG (glioma) and PA-1 (teratoma). The demonstration of 3'-isoLM1 in gliomas in in vivo forms and the relatively infrequent expression by derived cultured cells suggest that ganglioside expression is modified by environmental forces. Expression of 3'-isoLM1 and 3',6'-isoLD1 in fetal and neonatal brain, in intense reactive astrocytosis such as polyunsaturated fatty acid lipidosis, and in primary neoplasms of the central nervous system suggests their role in cell-cell attachment during development, migration, and neoplastic transformation.
Animals↗
Subclinical peripheral nerve involvement in AIDS: an electrophysiological and pathological study.
Thirty patients with AIDS without symptoms or signs of peripheral neuropathy were compared electrophysiologically with 23 age and sex matched healthy controls. The patients had a mean reduction in the amplitude of common peroneal compound muscle action potentials of 37% (95% CI 11-70%) and of sural sensory action potentials of 34% (CI 18-49%). Mean conduction velocity of both motor and sensory nerves was reduced by between 1 and 7 m/s, with a prolongation of F waves corrected for height of 5% in the arms and 13% in the legs. The distal motor latencies were unchanged. These changes did not correlate with the duration of AIDS, degree of immunosuppression (CD4 count), Body Mass Index, albumin or vitamin B12 level. Four patients had subclinical mononeuropathies. Sural nerve taken at necropsy from five asymptomatic AIDS patients had evidence of axonal degeneration without inflammation or demyelination. There was a mean reduction in myelinated fibre density of 30.5% (CI 10-51%) compared with eight age matched sudden death controls (p = 0.01). This loss principally affected the larger fibres. The pathological and electrophysiological changes indicate axonal degeneration and are similar to those seen in other chronic disorders and in normal ageing. It is concluded that this axonal degeneration is not specific to HIV.
Acquired Immunodeficiency Syndrome↗
Neuropathies in AIDS.
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Acquired Immunodeficiency Syndrome↗
Pathology--trends and pitfalls in histologic diagnosis, immunopathology, and applications of oncogene research.
Classifications of pediatric neoplasms of the CNS are evolving from morphology-based approaches, that seek a "cell of origin" or "phase of embryogenesis," to more complicated and flexible systems that incorporate the results of immunohistochemical and molecular biology investigations. Markers of cellular proliferation are being employed as well. The development of improved classifications will depend on a reasoned application of newer methodologies to complement and, if necessary replace, the many worthy aspects of present classifications. Careful coordination among clinicians, radiologists, and pathologists is necessary to establish the clinical relevance of these findings. Application of these classifications and the techniques that make them possible will help resolve many current important issues. Among these are the validity of the PNET approach to embryonal tumors; the criteria for classification and grading of ependymomas; and the utility of subdividing cerebellar astrocytomas. Other important issues include the regional incidence and histologic prognostic features in pilocytic astrocytomas, the clinicopathologic features of well-differentiated neoplasms and hamartomatous lesions that are now being detected by magnetic resonance imaging, the utility of subclassification of medulloblastoma, and the status as an entity of the primitive polar spongioblastoma. The increasing familiarity of clinicians, radiologists, and pathologists with existing and "new" clinicopathologic entities will minimize the likelihood that well-differentiated, slowly growing, or well-circumscribed neoplasms are overgraded and treated by unnecessarily aggressive therapy. Pathologists also need to be aware that certain nonneoplastic lesions can be misconstrued as neoplasms.
Biomarkers, Tumor↗
Monoclonal antibody and F(ab')2 fragment delivery to tumor in patients with glioma: comparison of intracarotid and intravenous administration.
Non-i.v. delivery of radiolabeled monoclonal antibodies (MAbs) has been shown to increase tumor uptake and decrease dose to normal tissues. In this study, we have examined the potential advantage of intracarotid (i.c.) versus i.v. administration for the delivery of an intact MAb and a F(ab')2 fragment to tumor in patients with gliomas. Three patients received 10-50 mg of 81C6 IgG2b, a MAb reactive with the glioma-associated extracellular matrix antigen tenascin, and three received 5-20 mg of the F(ab')2 fragment of Mel-14, which is reactive with gliomas and melanomas. Paired-injection protocols, in which one-half of the MAb was labeled with 131I and administered by i.c. injection, and one-half was labeled with 125I and simultaneously administered by i.v. injection, were used. For both 81C6 IgG2b and Mel-14 (Fab')2, no differences in blood clearance half-times or urinary excretion rates of radioiodine were observed between i.c.- and i.v.-administered activity. Analysis of biopsy samples revealed i.c.:i.v. uptake ratios of 1.02 +/- 0.04, 0.95 +/- 0.03, and 1.03 +/- 0.05 for the accumulation of 81C6 IgG2b in temporalis muscle, normal brain, and glioma, respectively. Similarly, the i.c.:i.v. uptake ratios for Mel-14 F(ab')2 in these tissues were 0.98 +/- 0.04 (SD), 1.00 +/- 0.05, and 1.04 +/- 0.05. When the differences in percentage of injected dose/g uptake after i.c. and i.v. administration were compared, no statistically significant advantage for i.c. delivery was seen (P = 0.22-0.61). These data indicate that i.c. administration of MAb 81C6 IgG2b and Mel-14 F(ab')2 fragments offers no delivery advantage to offset the small but finite risk involved in cannulation and injection of the internal carotid artery.
Antibodies, Monoclonal↗
Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis.
Neoplastic meningitis can result from leptomeningeal dissemination of a variety of cancers. We now report the development of animal models of human neoplastic meningitis and activity of intrathecal 4-hydroperoxycyclophosphamide (4-HC) against the human rhabdomyosarcoma cell line TE-671 and the human glioma cell line D-54 MG grown in the subarachnoid space of athymic rats. The injection of 5 x 10(5) TE-671 or D-54 MG cells resulted in leptomeningeal tumor growth from the base of the brain to the cauda equina. Daily weights and neurological examinations revealed progressive neurological deficits and weight loss, with death occurring between Days 21 and 27 for TE-671 and Days 14 and 26 for D-54 MG. 4-HC toxicity in non-tumor-bearing rats was assessed at dose levels of 2.0, 10.0, 15.0, and 20.0 mM, with clinical and histological evidence of neurotoxicity observed at the 2 highest dose levels. Intrathecal treatment with 4-HC on Day 8 following injection of TE-671 resulted in an increase in median survival of 20% (P = 0.04) at 1.0 mM 4-HC and 41% (P less than 0.001) at 2.5 mM 4-HC. Intrathecal treatment with 4-HC (2.5 mM) on Day 5 following injection of D-54 MG resulted in an increase in median survival of 23% (P = 0.009). These studies show the usefulness of the athymic rat model of human neoplastic meningitis and demonstrate the efficacy in vivo of intrathecally administered 4-HC against a human glioma and a human rhabdomyosarcoma cell line and the lack of toxicity at therapeutic levels of 4-HC in normal athymic rats.
Animals↗
Ganciclovir for lumbosacral polyradiculopathy in AIDS.
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Acquired Immunodeficiency Syndrome↗
Axonal atrophy in the painful peripheral neuropathy in AIDS.
We compared the sural nerves from patients with AIDS; four with the painful peripheral neuropathy (PPN), three patients with non-painful distal symmetrical peripheral neuropathy (DSPN), one without clinical peripheral nerve involvement and two human immunodeficiency virus negative controls. Fibre diameter distributions showed a slight reduction in larger fibres in all patients with AIDS compared with controls. No significant difference was found in the relative frequency distribution of the lamellae counts between any of the groups. The relative frequency distribution of axonal area of myelinated fibres did not differ between controls, non-painful DSPN or the patient without peripheral nerve involvement; however, all patients with PPN showed marked reduction in the number of axons of myelinated fibres of larger area which was significant when compared to each patient from the other groups (P less than 0.0001). This indicates that the reduction in larger fibres in PPN is mostly due to axonal atrophy rather than selective fibre loss. Axonal atrophy is associated with painful peripheral neuropathy in AIDS but not with those without pain. The possible role of axonal atrophy as a pathological substrate for pain is discussed.
Acquired Immunodeficiency Syndrome↗
Propranolol in acute migraine: a controlled study.
Propranolol is an established agent in migraine prophylaxis. Uncontrolled studies have suggested an action in the acute attack. We present the first double-blind placebo controlled study of propranolol in 27 unselected patients with common (migraine without aura) and classical (migraine with aura) migraine. There were 23 pairs of headaches in the 14 patients who completed the study. No difference was found, when the data were analysed by headache pair or by patient, in severity duration and subjective assessment of efficacy between those treated in an attack with propranolol 40 mg and placebo.
Acute Disease↗