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P Rudge

Publications and source records attributed to P Rudge.

At least 91 records · Page 5Linked to original sources
PubMed1990

Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications.

From an extensive serial magnetic resonance imaging (MRI) study in multiple sclerosis (MS) we have identified 4 cases in which disruption of the blood-brain barrier, as detected by gadolinium-DTPA enhancement, preceded other MRI abnormalities and in 1 case clinical evidence of the new lesion. This supports the view that a defect in the blood-brain barrier, and therefore inflammation, is an early and possibly crucial event in the pathogenesis of the new lesion in MS. These cases showed a marked discrepancy between MRI abnormality and symptoms. The mechanisms contributing to this disparity are discussed, and it is concluded that far from being surprising it is to be expected.

Adult↗
PubMed1990

In vivo cellular tropism of human T-cell leukemia virus type 1.

To establish the phenotype of human T-cell leukemia virus type 1 (HTLV-1)-infected cells in peripheral blood, the polymerase chain reaction was used to detect and quantitate viral DNA in subpopulations of leukocytes obtained from patients with tropical spastic paraparesis and asymptomatic carriers. HTLV-1 could not be detected in peripheral blood mononuclear cells thoroughly depleted of T lymphocytes (E- CD3-), nor could it be detected in highly enriched populations of B lymphocytes (E- CD19+), monocytes (E- CD14+), or natural killer cells (E- CD16+). T lymphocytes were strongly positive for HTLV-1, and fractionation of this population revealed that 90 to 99% of the HTLV-1 DNA segregated with the CD4+ CD8- and CD45RO+ subsets. No difference between the cell type distribution of HTLV-1 in the asymptomatic carrier and the subjects with tropical spastic paraparesis was evident. Southern hybridization of genomic DNA prepared from the peripheral blood of HTLV-1 carriers indicated that up to 10% of circulating leukocytes may carry the HTLV-1 provirus.

Blotting, Southern↗
PubMed1990

Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. I. Abducens palsy.

Fifty one patients with abnormalities of horizontal gaze were studied with magnetic imaging of the brain (MRI) and eye movement recordings to identify the loci of lesions responsible for isolated abducens palsy, conjugate gaze palsy and different types of internuclear ophthalmoplegias. The lesions responsible for a particular disorder were identified by overlapping enlarged drawings of the individual scans at comparable brain-stem levels and identifying the areas where the abnormal MRI signals intersected. A statistical procedure was devised to exclude the possibility that the areas of overlap occurred by chance. In this paper, the findings in the group of patients with VI nerve palsy are reported since the location of their lesions could be predicted from known anatomy, so validating the procedure. The results were independently obtained with the overlapping technique and the statistical procedure and showed that the lesions were located in a region corresponding to the posterior part of the abducens fasciculus. This confirms that central lesions producing isolated lateral rectus weakness spare the abducens nuclei. The agreement between the procedures used and earlier clinical and experimental results suggest that the method we describe can be applied to locate the site of lesions on MRI scans in other groups of patients with more complex gaze disorders.

Abducens Nerve↗
PubMed1990

Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. II. Gaze palsy and internuclear ophthalmoplegia.

The site of lesions responsible for horizontal gaze palsy and various types of internuclear ophthalmoplegia (INO) was established by identifying the common areas where the abnormal MRI signals from patients with a given ocular-motor disorder overlapped. Patients with unilateral gaze palsy had lesions in the paramedian area of the pons, including the abducens nucleus, the lateral part of the nucleus reticularis pontis caudalis and the nucleus reticularis pontis oralis. Patients with abducens nucleus lesions showed additional clinical signs of lateral rectus weakness. Lesions responsible for bilateral gaze palsy involved the pontine tegmental raphe. Since this region contains the saccadic omnipause neurons, this finding suggests that damage to omnipause cells produces slowing of saccades rather than opsoclonus, as previously proposed. All INOs, regardless of the presence of impaired abduction or convergence, had similar MRI appearances. Frequently the lesions in patients with INO, were not confined to the medial longitudinal fasciculus (MLF) but also involved neighbouring structures at the pontine and mid-brain levels. There was a statistically significant association between the clinical severity of the INO and the presence of abnormal abduction or convergence. The findings suggest that the lesions outside the MLF, which may affect abducens, gaze or convergence pathways, are responsible for the presence of features additional to INO, depending on the magnitude of functional disruption they produce.

Abducens Nerve↗
PubMed1990

Hemiparetic multiple sclerosis.

Eight patients are described who presented with hemiparesis which involved the face in seven. Six of the eight subsequently developed clinically definite multiple sclerosis and in the remaining two patients multiple sclerosis was the likely diagnosis. Magnetic resonance imaging gave useful information about the site of the lesions responsible for the presenting syndrome and provided additional information in support of a diagnosis of multiple sclerosis.

Adult↗
PubMed1990

Heterogeneity of blood-brain barrier changes in multiple sclerosis: an MRI study with gadolinium-DTPA enhancement.

We performed 15 dynamic gadolinium-DTPA (Gd-DTPA)-enhanced MRI studies in 8 patients with relapsing and remitting multiple sclerosis; 7 were follow-up studies. We measured the time course of enhancement in 102 enhancing lesions for up to 384 minutes, with rest breaks. Immediate postcontrast MRIs demonstrated many different patterns of enhancement. We observed both uniformly enhancing and ring enhancing lesions. The enhancing regions were often less extensive than the corresponding high signal on T2-weighted images. Three lesions were seen with Gd-DTPA but not on unenhanced scans; 1 was seen on unenhanced scans 10 days later, suggesting that blood-brain barrier disturbance may precede other MRI signs of MS lesions. Three months later, some high-signal areas on T2-weighted scans had decreased in size to resemble the areas previously outlined by Gd-DTPA. This technique provides useful information about the pathogenesis and behavior of MS lesions.

Adolescent↗
PubMed1990

The neurological complications of Anderson-Fabry disease (alpha-galactosidase A deficiency)--investigation of symptomatic and presymptomatic patients.

Anderson-Fabry disease is an X-linked inborn error of metabolism characterized by subnormal activity of the lysosomal hydrolase, alpha-galactosidase A. We have assessed the incidence and nature of neuropathy in 12 patients (seven affected men and five carrier females). Abnormalities of cutaneous thermal sensation were common, even in asymptomatic carriers, with a unique predilection for cold sensitivity which suggests involvement of small myelinated nerve fibres. Intracranial abnormalities were frequently detected by magnetic resonance imaging (MRI) in males, both with and without overt cerebrovascular disease, and were more extensive in older patients. Such abnormalities were not detected in carriers. Auditory and vestibular abnormalities were present in six patients, only one of whom was symptomatic. Cranial MRI and assessment of cutaneous thermal thresholds are sensitive techniques which can identify neurological involvement in asymptomatic patients. They may be of benefit in monitoring the effectiveness of enzyme replacement therapy and excluding the carrier state for the defective gene.

Adolescent↗
PubMed1989

The early risk of multiple sclerosis following isolated acute syndromes of the brainstem and spinal cord.

A combined clinical and magnetic resonance imaging follow-up study was undertaken to determine the risk of early progression to multiple sclerosis in patients who present with clinically isolated lesions of the brainstem or spinal cord. Progression to multiple sclerosis was seen in 13 patients (57%) who had a brainstem syndrome and in 14 patients (42%) who had a spinal cord syndrome after mean intervals of 15 and 16 months, respectively. The risk of progression was increased by the presence of oligoclonal bands in the cerebrospinal fluid of patients with either syndrome and by the presence of disseminated brain lesions, as detected by magnetic resonance imaging, in those with a spinal cord syndrome. Follow-up revealed evidence of multiphasic disease in 24 (69%) of 35 patients who had disseminated lesions on magnetic resonance imaging scans at presentation, suggesting that multiple sclerosis is the usual cause of such lesions.

Adult↗
PubMed1989

Viral specific IgG and IgM antibodies in the CSF of patients with tropical spastic paraparesis.

The cerebrospinal fluid (CSF) from seven West Indian migrants to the United Kingdom with tropical spastic paraparesis were studied by antigen immunoblotting for specific anti-HTLV1 oligoclonal IgG and IgM. Eight CSFs from five patients were positive for specific IgG and negative for IgM; three CSFs from two patients were positive for IgM and negative for IgG. No patient had both IgG- and IgM-positive CSF. Those patients with IgM only had disease of the shortest duration. When looking for evidence that neurological damage is caused by HTLV1, both IgM and IgG should be examined.

Adult↗
PubMed1989

Tropical spastic paraparesis and human T cell lymphotropic virus type 1 in the United Kingdom.

Twenty-one patients with tropical spastic paraparesis (TSP), all of whom were born in the Caribbean and who had migrated to the United Kingdom, are described. All had a progressive spastic paraparesis developing many years after immigration and all 19 tested had antibodies to the human T cell lymphotropic retrovirus type 1 (HTLV1). The clinical and laboratory features and visual, auditory and somatosensory evoked potentials are described. Details of magnetic resonance scanning of the brain and, in a few cases, the spinal cord are compared with those found in multiple sclerosis. The antibody titres to HTLV1 assessed by particle agglutination, Western blot, antibody-directed cell mediated cytotoxicity and pseudotype neutralization were higher than in asymptomatic infected relatives and in patients with adult T cell leukaemia. Some, but not all, of the IgG oligoclonal bands in the CSF were directed against HTLV1. IgM oligoclonal bands directed against HTLV1 were found in 2 patients. Sixty of the 64 first degree relatives of 11 Jamaican patients with TSP were traced in the UK and the Caribbean; 20-30% of those born in the Caribbean had antibodies to HTLV1, irrespective of their present place of residence, whilst none of those born in the UK, who were the children of the patients, had antibodies. The original pathological material obtained from the Caribbean by Montgomery et al. (1964) is reviewed. These results are discussed in relation to animal retroviral neurological diseases, particularly visna in sheep which has clinical and pathological features closely similar to TSP. It is proposed that TSP is due to a HTLV1 infected lymphocyte/macrophage immune-mediated inflammatory response in the spinal cord.

Adult↗
PubMed1989

Ocular inflammatory changes in established multiple sclerosis.

Fifty consecutive patients with clinically definite multiple sclerosis were studied to assess the prevalence of concomitant uveitis. Asymptomatic ocular inflammatory changes were found in nine patients (18%) and appeared to show a positive correlation with severe and progressive disease. Conversely uveitis was uncommon in the presence of established optic atrophy which suggests a negative influence on its pathogenesis. In the absence of optic atrophy inflammatory changes in the eye may be a valuable index of disease activity.

Adolescent↗
PubMed1989

Cyclosporin A curtails the progression of free light chain synthesis in the CSF of patients with multiple sclerosis.

Free light chains in the cerebrospinal fluid of patients with multiple sclerosis correlate closely with disease activity. As part of a double-blind placebo controlled trial of immunosuppression using cyclosporin A in patients with multiple sclerosis, light chain analysis was performed on pre- and post-treatment CSF samples in 19 patients, nine having received cyclosporin A and 10 placebo. The placebo treated patients showed continued immunological activity, as evidenced by an increase in both free kappa and lambda chains, but cyclosporin A treatment resulted in no change or an improvement in light chain response, indicative of suppression of continued activity. As cyclosporin A does not enter the CSF, this implies that systemic stimulation is at least partly responsible for continued disease activity in multiple sclerosis. Cyclosporin A may thus be effective in preventing the deterioration of patients with multiple sclerosis.

Adult↗
PubMed1989

Randomised double blind controlled trial of cyclosporin in multiple sclerosis.

In a 2 year double blind controlled trial of cyclosporin against placebo in multiple sclerosis conducted at two centres there was a beneficial effect of the therapy upon the progression of the disease, relapse rate and relapse severity at one of the centres where the patients received a mean dose of 7.2 mg/kg/day. This beneficial effect was not seen in the other centre where a lower dose (mean 5 mg/kg/day) was given. Reduction in clinical progression was accompanied by decreased IgG synthesis in the central nervous system. Side effects included hypertension, renal insufficiency and anaemia and were of such severity to preclude the use of cyclosporin in a high enough dose to alter the course of the disease.

Adolescent↗