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Biomedical subjects

D A Compston

Publications and source records attributed to D A Compston.

At least 109 records · Page 6Linked to original sources
PubMed1988

Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales.

A population-based study in south-east Wales (population 668,100) identified 135 patients with von Recklinghausen neurofibromatosis (prevalence 20/10(5]. In addition to multiple café-au-lait spots and/or dermal neurofibromas, freckling was present in the axilla (67%), groin (44%) or submammary areas (29% of adult females). Although not a criterion for diagnosis, Lisch nodules were almost invariably present in the iris (93% of patients overall; 96% of those aged greater than or equal to 20 yrs). The complications of von Recklinghausen neurofibromatosis in this cohort (n = 135 unless stated) were plexiform neurofibromas (40/125), severe mental retardation (1), epilepsy (6), optic glioma (2), spinal neurofibroma (2), aqueduct stenosis (2), meningioangiomatosis (1), scoliosis requiring surgery (6), pseudoarthrosis (3), delayed puberty (2), visceral and endocrine tumours (6), and congenital glaucoma (1). There were no cases of acoustic neuroma. Considering all living family members aged greater than or equal to 18 yrs, together with their deceased relatives, the frequency of CNS and malignant tumours related to the disease was 4.4-5.2%. Uncomplicated von Recklinghausen neurofibromatosis is disfiguring but not a major cause of morbidity. The management of the disease relates to its complications which can be divided into three categories: those which occur in childhood and cause lifelong morbidity (moderate-severe mental handicap, facial plexiform neurofibromas, orthopaedic), those which can occur at any time but are 'treatable' (benign disorders of the nervous system, visceral and endocrine tumours, renal artery stenosis), and malignant or CNS tumours. The combined frequency for each category based on this survey was 12%, 16% and 4.4-5.2%, respectively.

Adolescent↗
PubMed1988

The prevalence of multiple sclerosis in south east Wales.

A population-based survey of multiple sclerosis in the county of South Glamorgan has demonstrated a prevalence of 441/376718 (117/10(5)). Eighty six per cent of the patients (101/10(5)) had definite or probable disease and 14% (16/10(5)) had suspected multiple sclerosis on 1 January 1985. The estimated average incidence is 5.41/10(5)/year for the period 1947-84 and it has risen significantly over four decades. The prevalence is similar to that found in a recent survey from the south east of England but significantly lower than revised figures from Scotland.

Adolescent↗
PubMed1988

Spontaneous carotid cavernous fistula in Ehlers Danlos syndrome.

A patient is described with Ehlers Danlos syndrome presenting with spontaneous carotid cavernous fistula, in whom there was biochemical evidence for defective type III collagen synthesis. Despite the risks associated with arterial manipulation, the fistula was successfully closed by interventional neuroradiology and the patient has since remained well. This outcome is in contrast with the results in previous reports.

Adult↗
PubMed1988

Peripheral blood lymphocyte phenotype and function in multiple sclerosis.

T suppressor cell function and phenotype are abnormal in patients with multiple sclerosis, especially during the chronic progressive phase but the sub-populations defined by mitogen stimulation and serological methods may not be identical. In this study, involving 45 patients with multiple sclerosis and 33 controls, there was no correlation between T suppressor function and CD8 cell phenotype in patients with multiple sclerosis or in controls. These phenotypic and functional studies cannot therefore be used interchangeably in the assessment of patients with multiple sclerosis since they provide different information about lymphocyte subpopulations.

Antibody Formation↗
PubMed1988

Inflammatory demyelinating polyneuropathy in a haemophiliac associated with human immunodeficiency virus infection, responding to high dose intravenous immunoglobulin.

We describe what we believe to be the first case of chronic inflammatory demyelinating polyneuropathy (CIDP) occurring in a haemophiliac infected with the human immunodeficiency virus (HIV), and the first patient to show a clinical response to treatment with high dose i.v. immunoglobulin. A 55 year old, severe haemophiliac, known to be positive for HIV antibody, presented with a short history of motor weakness and variable sensory loss in both lower limbs. Clinical examination, electrophysiology and sural nerve biopsy confirmed a diagnosis of CIDP. He was treated with a 4-day course of high dose i.v. immunoglobulin, given as a daily infusion. This resulted in dramatic improvement in his neurological status which was evident both clinically and functionally. We conclude that CIDP can occur in HIV-positive haemophiliacs as it does in homosexuals and drug abusers infected with the virus. We also suggest that high dose i.v. immunoglobulin may be effective in the treatment of this condition, especially when practical difficulties preclude the use of plasmapheresis and the use of immunosuppressive drugs is considered hazardous.

Demyelinating Diseases↗
PubMed1987

A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. Clinical effects.

A randomised double-blind, placebo-controlled trial of high-dose, pulsed intravenous methylprednisolone was carried out in 50 individuals with multiple sclerosis; 22 patients were in acute relapse and 28 had chronic progressive disease. After a baseline assessment using the Kurtzke functional and expanded disability status scales each patient was randomly allocated to intravenous treatment with methylprednisolone (500 mg) or a saline placebo administered as a single daily dose for 5 days. Clinical assessments were repeated at 1 and 4 weeks after starting treatment. The results from all 50 patients showed a highly significant effect in favour of methylprednisolone treatment (p less than 0.001). In patients with relapse, there was a significant decrease in clinical disability scores at 1 and 4 weeks in the methylprednisolone treated group compared with controls (p less than 0.05 for each comparison). In the chronic progressive group, disability scores at 4 weeks only were significantly lower after treatment with methylprednisolone (p less than 0.01), mainly attributable to improvement in pyramidal function.

Adolescent↗
PubMed1987

A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 2. Laboratory results.

Laboratory measurements were compared in paired samples from 50 patients included in a double-blind placebo controlled trial of methylprednisolone in the treatment of multiple sclerosis. Cerebrospinal fluid total cell count, IgG and C9 indices, and percentage of peripheral blood OKT8 positive cells were abnormal at entry and returned closer to the normal range after active than placebo treatment, but the differences were not statistically significant. The percentage of peripheral blood OKT4 positive cells was normal at entry as was the amplitude of visual evoked potentials, whereas their latency was prolonged; these measurements were each uninfluenced by methylprednisolone. Corticosteroids might act merely by influencing oedema, but the laboratory results suggest that methylprednisolone affects immunological events which underly rapid onset and recovery of symptoms in patients with multiple sclerosis; additional forms of treatment are needed to maintain these clinical and immunological effects.

Adolescent↗
PubMed1987

A reassessment of the risk of multiple sclerosis developing in patients with optic neuritis after extended follow-up.

One hundred and one of 146 patients presenting with isolated idiopathic optic neuritis, previously reviewed in 1978, were reassessed clinically, and retyped for HLA antigens and Factor B alleles, after a mean follow-up of 11.6 years. Fifty eight patients (57%) had developed multiple sclerosis at the time of reassessment in the present study, of whom 51 (88%) had clinically definite disease. This compared with 40% of the original group, in 1978, of whom 62% then had clinically definite multiple sclerosis. When the life-table method of analysis was used, the probability of developing multiple sclerosis was 75%, 15 years after the initial episode of optic neuritis. The frequencies of HLA-DR2 and the recently defined D-region antigen, DQw1, were significantly increased in patients with isolated optic neuritis and those who subsequently developed multiple sclerosis compared with normal controls, but neither allele appears to influence progression from optic neuritis to multiple sclerosis. Patients with optic neuritis who were HLA-DR3 positive had an increased risk for the development of multiple sclerosis (RR = 2.8) and this risk was further enhanced when DR3 occurred in combination with DR2 (RR = 6.7). The overall increased risk of developing multiple sclerosis for patients with this combination was 26 times that for the normal population. When the patients' original tissue-typing was considered BT 101 no longer influenced conversion of optic neuritis to multiple sclerosis. This may partly be explained by improved methods of tissue-typing, since not all BT 101 patients were subsequently found to be positive for HLA-DR2 or HLA-DQw1 and vice versa and by extended follow-up as multiple sclerosis conversion in HLA-DR2 negative individuals increased with time. All 101 patients were typed for Factor B alleles. No significant differences in frequencies were found between individuals with isolated optic neuritis or those who progressed to multiple sclerosis compared with the control population. Recurrent episodes of optic neuritis were associated with an increased risk for the development of multiple sclerosis in this study.

Adolescent↗
PubMed1987

HLA and multiple sclerosis in south east Wales.

A stronger association has been found between multiple sclerosis and HLA-DR2 than -DQwl in south east Wales (prevalence c 113/10(5)) in contrast to recent observations in north east Scotland (prevalence 178/10(5). The complex relationship between the HLA system and multiple sclerosis, demonstrated in this and other studies, is explained more easily under a polygenic model of inheritance, in which environmental events and genes interact, than by the presence of a single susceptibility gene.

Gene Frequency↗
PubMed1987

Factors influencing circulating OKT8 cell phenotypes in patients with multiple sclerosis.

Peripheral blood OKT8 cell phenotypes were correlated with measurements of plasma cortisol and serological evidence for exposure to 15 infectious agents, in longitudinal studies involving 13 patients with multiple sclerosis, 13 of their siblings, nine spouses and 13 unrelated controls; 44/48 individuals were HLA typed. Neither circadian rhythms, nor exposure to any one infectious agent accounted for the serial changes in OKT8 cells but there was an association between the presence of HLA-DR2 and periodic reductions in OKT8 cells irrespective of clinical status. Taken with previously reported serial observations in patients and cohabiting relatives, this finding provides indirect evidence for an interplay between environmental and genetic factors in determining OKT8 cell phenotypes in multiple sclerosis.

Antibodies↗
PubMed1987

The multiple causes of multiple sclerosis: the importance of age of infections in childhood.

The geographic distribution of multiple sclerosis (MS) may relate to the age of initial exposure and degree of sensitization to common viruses or bacteria which have proteins with epitopes (antigenic determinants) which are homologous with potentially encephalitogenic peptides in central myelin proteins, such as basic protein and proteolipid protein. Comparable homologies may exist for the as-yet-undefined nonencephalitogenic myelin antigen(s) which evoke demyelinating factors (probably complement-fixing antibodies). Many of these homologous epitopes occur in microorganisms that also possess adjuvant activity for evoking not only the sensitized T-cells but also the antibodies that cross-react with the target antigens in central myelin. If sufficient sensitization to myelin basic protein or proteolipid protein occurs, especially in infections of young adults, the individual develops acute disseminated encephalomyelitis, exactly comparable to ordinary acute experimental allergic encephalomyelitis (EAE). If very young children are infected, however, practically complete resistance develops, and neither acute disseminated encephalomyelitis nor MS follows. In between these two extremes, especially in slightly older children in whom insufficient sensitization occurs to induce acute disseminated encephalomyelitis, the individual may become resistant to acute disseminated encephalomyelitis, but susceptible to chronic relapsing or progressive disseminated encephalomyelitis, otherwise generally recognized as MS. This is exactly comparable to a recently described variant of chronic EAE in which demyelinating antibodies and large subpial plaques of demyelination occur. The similarity of this form of chronic EAE or chronic disseminated encephalomyelitis to one form of MS is emphasized.

Antigens, Bacterial↗
PubMed1986

Viral infection in patients with multiple sclerosis and HLA-DR matched controls.

Retrospective comparisons of the prevalence and age, where appropriate, of some childhood infectious illnesses and vaccinations, together with serological evidence for exposure to 16 viruses, many of which have previously been implicated in the aetiology of multiple sclerosis (MS) were made in 177 patients with acute optic neuritis, other recent isolated demyelinating episodes or established MS and 164 controls. The expected high frequency of HLA-DR2 in patients with demyelinating disease was matched by preselection of normal controls with this antigen (DR2+); the remaining individuals were classified as HLA-DR2 negative/DR3 positive (DR3+) or HLA-DR2 and 3 negative (DR2/3 -). Cases were compared with controls, collectively and in analyses restricted to each genetic group; these comparisons were repeated considering the three categories of patients with demyelination and two control populations separately. All DR2+, DR3+ and DR2/3 - individuals were compared in a single analysis to assess the effect of HLA type itself on the results. Patients with demyelinating disease had rubella and measles at a later age and reported mumps infection more frequently than controls. Age of typhoid vaccination and duration of exposure to domestic dogs was higher in all cases than controls. Age of measles and mumps, but not rubella, was higher in DR2+ cases than controls; but differences were not observed in the other genetic groups. Higher rubella antibody titres were present in all cases than controls and in analyses confined to DR2+ individuals in whom higher Epstein Barr virus antibody titres were also present. Measles haemagglutination inhibition and parainfluenza I antibody titres were increased and influenza A antibodies detected less frequently in all patients with optic neuritis and those with DR2 compared with appropriate controls; influenza B antibody titres were lower in all DR2+ cases than controls. Higher adenovirus and varicella zoster antibody titres were present in DR2/3- patients with demyelination and other neurological diseases compared with normal controls. Overall, older age of infection and higher antibody titres were observed more often in patients with optic neuritis, in particular DR2+ cases, than other individuals with demyelination or controls. Our serological results are consistent with the presence of abnormal HLA-immunological reactivity in patients with MS but cannot be explained only by an effect of DR type itself; age at which susceptible individuals develop some common childhood infections may also influence the subsequent development of the disease.

Adult↗
PubMed1986

Suppressor T cells in family members of patients with multiple sclerosis.

Previous serial measurements of lymphocyte subpopulations in individuals with multiple sclerosis (MS) have demonstrated periodic reductions in the number of OKT8 positive (T8+) cells. In this longitudinal study, involving twice monthly samples from each participant and carried out in two phases lasting at least six and three months respectively, we have confirmed that fluctuations in T8+ cells occur in patients with MS and also found a significant reduction in this lymphocyte subpopulation in patients' spouses but not their siblings, compared with unrelated controls. The changes observed in spouses were related in time to those occurring in patients on 10/13 occasions from 5/9 families; no temporal relationship occurred in the remainder. Taking two or more low T8+ values as significant, 12/13 patients, 7/9 spouses, 6/13 siblings and 4/13 controls (chi 2 = 12.5; P less than 0.01) were abnormal at some stage. Our results provide indirect evidence for the role of environmental factors in determining certain immunological abnormalities present in patients with MS and illustrate the role of family studies in determining the specificity of these changes to the disease.

Adult↗
PubMed1986

Cerebellar haemangioblastoma and von Hippel-Lindau disease.

Von Hippel-Lindau disease is an autosomal dominant multisystem disorder, the commonest presenting manifestations of which are haemangioblastomas of the cerebellum and retina. Affected individuals are at risk of developing a number of other lesions, the most serious of which are renal carcinoma, haemangioblastomas elsewhere in the central nervous system and phaeochromocytoma. Patients with this disease can therefore present to a number of disciplines during their lifetime and unless the possibility of von Hippel-Lindau disease is considered, the patient may wrongly be assumed to have an isolated lesion. Twenty patients with cerebellar haemangioblastomas were seen between 1972 and 1985; the diagnosis of von Hippel-Lindau disease was subsequently established in 8. Although the diagnosis had not previously been considered, in retrospect 7/8 cases were known to be at risk of this syndrome. These cases came from 7 families and an additional 4 relatives are also known to have been affected. Mean age of presentation for the various manifestations of von Hippel-Lindau disease, each of which occurred in one or other of our cases, has been calculated from 9 of our patients and 107 others reported in the literature. Clinically significant manifestations almost invariably developed before the age of 50 years. Limited screening of our index cases and their at-risk relatives demonstrated one asymptomatic renal carcinoma. We propose a protocol for screening all individuals at risk of von Hippel-Lindau disease, which involves annual retinal examination from five years, and biennial computerized tomography of the head and abdomen from fifteen and twenty years, respectively.

Adolescent↗
PubMed1986

Linkage analysis of peripheral neurofibromatosis (Von Recklinghausen disease) and chromosome 19 markers linked to myotonic dystrophy.

Three chromosome 19 markers known to be linked to myotonic dystrophy have been studied in nine families with peripheral neurofibromatosis (Von Recklinghausen's disease). Clear evidence against linkage has been found for all three markers, excluding the peripheral neurofibromatosis gene from the myotonic dystrophy region of chromosome 19. Previous reports of co-inheritance of the two disorders in families cannot therefore be explained on the basis of close genetic linkage between the loci.

Adult↗