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Biomedical subjects

P Rudge

Publications and source records attributed to P Rudge.

At least 109 records · Page 6Linked to original sources

Familial multiple sclerosis.

Siblings of patients with multiple sclerosis have an increased risk of developing the disease. In this report we describe 3 families with multiple affected members, representing the largest published aggregation of cases in first degree relatives. In the 2 families in which HLA tissue-typing was performed the affected individuals shared part of the haplotype HLA-DR2 (+ HLA-DQW1), BfS (+ C2C), C4A3, C4B1. The implications of these findings for the aetiology of multiple sclerosis are discussed.

Adolescent↗

Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis.

Serial gadolinium-DTPA (Gd-DTPA) enhanced magnetic resonance imaging (MRI) was performed in 9 patients with multiple sclerosis (MS). On the first scan enhancing lesions were seen in 7 patients, all of whom were in acute relapse. Most enhancing lesions were asymptomatic. On the second scan (3 to 5 weeks later), persisting enhancement was seen in only 12/54 lesions which enhanced on the first scan. No lesion showed persisting enhancement on the third scan (after 6 months). Enhancement occurred in all 12 new lesion areas seen on the unenhanced second scan and in 8 of 15 new lesions seen on the third scan. Enhancement was also seen in 4 older lesions which had been nonenhancing on earlier scans. Relaxation time measurements demonstrated a high water content in some nonenhancing lesions, which could be due to a subtle blood-brain barrier disturbance not detected with Gd-DTPA. The results show that blood-brain barrier impairment is a consistent finding in new MS lesions detected with MRI. Gd-DTPA is a useful marker of new and biologically active lesions and should prove of value in monitoring therapeutic trials in MS.

Adult↗

The effects on auditory function of damage to the pontine olivo-cochlear bundle in man.

A patient with multiple sclerosis (MS) in whom a lesion developed in the pons between successive nuclear magnetic resonance image scans (MRI) is described. The patient developed intolerance of loud sounds, with distorted perception of speech and music, and abnormalities of stapedius reflex threshold, masked speech audiometry, and masking level difference assessment in the presence of an unchanged pure tone threshold. These abnormalities partially resolved over a number of months. It is postulated that the efferent olivo-cochlear bundle was involved on one side of the pons and the abnormalities are interpreted in terms of bilateral removal of inhibition from the hair cells of the cochlea.

Adult↗

The site of the lesion causing deafness in multiple sclerosis.

A patient with multiple sclerosis who developed sequential hearing loss, first on the right, with recovery is discussed. Magnetic resonance imaging demonstrated lesions in the VIII nerve root entry zones which were thought to be responsible for the hearing loss.

Deafness↗

Cyclosporine and multiple sclerosis: the cons.

Although the pathophysiologic cause of multiple sclerosis (MS) is unknown, there is a considerable body of evidence that immunologic factors play a part. As experimental allergic encephalomyelitis (EAE), particularly its relapsing and remitting forms, has some similarities to MS, and because EAE can be modified by immunosuppression, a large number of immunomodulating drugs have been given to patients with MS. None of these therapies has been dramatically successful, but immunosuppression with azathioprine, mercaptopurine, and cyclophosphamide have been of marginal benefit to the patients. The reason for this relative failure of such therapy in MS might be because these conventional immunosuppressants do not sufficiently modify the immunologic abnormalities in the patients. Cyclosporine A is the first of a new generation of immunosuppressants that appear to be more potent, at least in the field of transplantation. For this reason, it is logical to determine its efficacy in MS. Based on the hypothesis that MS is an immunopathologic disease, many immunosuppressive therapies have been tried for this condition. Cyclosporine is the newest such agent. Studies in animals with EAE indicate that the drug suppresses the disease, but when the drug is stopped the disease exacerbates. This may also happen in MS. Furthermore, our studies indicate that cyclosporine has a low therapeutic index, so that in doses that are well tolerated the drug is not effective and in doses that are effective there is significant toxicity. For these reasons, we reluctantly conclude that cyclosporine should not be used in MS.

Clinical Trials as Topic↗

Antibody to human T-lymphotropic virus type 1 in West-Indian-born UK residents with spastic paraparesis.

Of 13 West-Indian-born UK residents with spastic paraparesis of unknown cause, 11 were tested for serum antibody to human T-cell lymphotropic virus type 1 and all were positive. Their magnetic resonance imaging scans were normal or showed only minor abnormalities in the brain, and the spinal cord was normal in the 5 investigated. Of 48 patients with multiple sclerosis, mainly caucasian, none had antibody to HTLV-1 in the blood.

Adult↗

Acute myelopathy associated with primary infection with human immunodeficiency virus.

A 29 year old white homosexual man presented with a two and a half week history of severe sore throat, fever, and extreme fatigue. His symptoms did not respond to antibiotics. He had mild bilateral conjunctivitis, a rash over his chest and back, and enlarged lymph nodes, but examination of the nervous system yielded normal results. He had low total white cell and platelet counts. The results of enzyme linked immunosorbent assay for human immunodeficiency virus (HIV) were equivocal when HIV IgM was detected in serum. Despite treatment with ampicillin his temperature remained high and he developed abnormal neurological signs, including a paraparesis and hyperreflexia of the arms. HIV was isolated from lymphocytes from blood and cerebrospinal fluid. Over the next six weeks the patient improved and was discharged. Two months later abnormal neurological signs persisted in his legs. Although various neurological syndromes associated with seroconversion to HIV have been described, this is probably the first report of a patient with myelopathy at the time of seroconversion.

Adult↗

MR brain scanning in patients with vasculitis: differentiation from multiple sclerosis.

We performed MR (magnetic resonance) brain imaging on 24 patients with a systemic vasculitis. MRI proved to be a sensitive method for detecting brain lesions (clinically silent or manifest) in these patients. The most frequent abnormalities were periventricular lesions seen in 12 cases. Such changes are not specific for vascular disease, and are often seen in multiple sclerosis. However, additional changes were commonly seen which suggested the correct diagnosis.

Adolescent↗

Central and peripheral SEP defects in neurologically symptomatic and asymptomatic subjects with low vitamin B12 levels.

Somatosensory evoked potentials (SEPs) following median nerve stimulation were abnormal in 7 patients with sensory impairment due to vitamin B12 deficiency. Extensor plantar reflexes indicated a central sensory pathway lesion in 4 cases and absent tendon jerks suggested peripheral neuropathy in 4, but median nerve SEPs indicated a predominantly central lesion without marked peripheral nerve involvement in 6 and an axonal neuropathy without CNS involvement in 1. The latter had evidence of central slowing of conduction in SEPs following posterior tibial nerve stimulation. Consequently, it is suggested that the brunt of sensory pathway involvement usually falls on the CNS, although peripheral neuropathy may occur as the major abnormality in some cases. In 2 patients SEPs showed a marked improvement following treatment with vitamin B12 injections, one consistent with restored central conduction and the other with recovery from peripheral neuropathy. No peripheral or central SEP abnormalities were seen in 18 dairy-produce eating vegetarians with low vitamin B12 levels, although 6 reported mild sensory symptoms suggestive of peripheral neuropathy and 3 had corroborative clinical signs.

Adolescent↗

Down beating nystagmus: magnetic resonance imaging and neuro-otological findings.

Twenty-four patients with down beating nystagmus (DBN) underwent magnetic resonance imaging (MRI) of the head. MRI provided diagnostic images in Arnold-Chiari malformation (6 cases), cerebellar atrophy (6 cases), 1 case with a prepontine-medullary epidermoid tumour and was helpful in the diagnosis of 2 patients with multiple sclerosis and 1 with a ponto-cerebellar infarct. Multiple cerebral hemisphere lesions were found in 6 patients (5 of them over 60 years of age) in whom no diagnosis was made. All cases of DBN, plus 3 additional patients with Arnold-Chiari malformation and other types of nystagmus, were neuro-otologically assessed. Sensitivity of the nystagmus to head tilt with respect to the gravity vector had no localizing value. Impaired horizontal vestibulo-ocular reflex suppression occurred more frequently in those patients with abnormal posterior fossa MRI. Pure torsional nystagmus, and DBN with a strong torsional component, in patients with Arnold-Chiari malformation was associated with syringomyelia. Magnetic resonance is the imaging method of choice for investigating patients with DBN.

Adolescent↗

Chronic demyelinating peripheral neuropathy associated with multifocal central nervous system demyelination.

A series of 6 cases is described in which a chronic demyelinating neuropathy was associated with a relapsing multifocal CNS disorder, the clinical features of which resembled multiple sclerosis. Multifocal CNS lesions were demonstrated by CT and MR imaging and the presence of CNS demyelination was indicated by prolonged central conduction times. These cases are discussed in relation to the occurrence of combined peripheral and central demyelination in chronic relapsing experimental allergic encephalomyelitis and neuritis.

Action Potentials↗

The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study.

The form and distribution of MRI abnormalities in 114 patients with clinically definite multiple sclerosis (MS) have been compared with observations on 53 apparently healthy individuals, 129 patients with isolated focal neurological lesions with which MS often presents (51 patients with optic neuritis, 44 with isolated brainstem lesions and 34 with isolated spinal cord syndromes) and 105 patients with disorders which may be confused clinically or radiologically with MS. The latter comprised 55 patients with cerebral vascular disease (including 7 cases of dementia with diffuse white matter disease), 24 with degenerative ataxic disorders, 8 with cerebellar tonsillar ectopia, 7 with sarcoidosis and 11 with a variety of other disorders. Periventricular abnormalities were found in all but 2 patients with MS and discrete white matter lesions in all but 12. Characteristically the periventricular changes in MS were irregular in outline. Periventricular abnormalities which were often milder and of smooth outline were seen in 37/55 patients with cerebral vascular disease, 9/24 with cerebellar degeneration, 5/7 with sarcoidosis and in 2/3 apparently healthy individuals over the age of 60. The appearances in the 7 cases of dementia resembled those with advanced MS. Cerebellar and/or brainstem atrophy characteristic of the cerebellar degenerations, in the absence of white matter abnormalities, was helpful in making the distinction from MS. Congenital anomalies and tumours in the region of the brainstem and foramen magnum were readily shown. More than half the patients with symptoms attributable to isolated focal neurological lesions had additional lesions at presentation. MS cannot be diagnosed in these cases at presentation, but repeat scans after 5 to 20 months in 25 patients with optic neuritis and 10 with clinically isolated brainstem lesions have shown new lesions in 7 (20%). The patients with new lesions fulfil the criteria for clinically probable MS (Poser et al., 1983). Measurements of T1 and T2 in vivo permitted the distinction of acute from chronic brainstem lesions. There were quantitative differences in T1 and T2 between the normal appearing white matter in MS and normal brain. Studies of postmortem brains provided convincing evidence that the MRI abnormalities in MS correspond with plaques. Evidence is adduced to support the view that an important source of the abnormal NMR signals in acute lesions is oedema, and in chronic lesions is gliosis; demyelination per se is unlikely to make an important contribution.

Adolescent↗

Spasmodic torticollis following unilateral VIII nerve lesions: neck EMG modulation in response to vestibular stimuli.

Three patients with spasmodic torticollis following VIII nerve lesions (VIII-ST) underwent quantitative assessment of their sternomastoid EMG during vestibular (otolith and semicircular canal) stimulation. The results were compared with a normal control group and with six patients with idiopathic spasmodic torticollis (ST). Backwards tilt of the VIII-ST patients resulted in a marked increase in the EMG, especially in the more affected sternomastoid, whereas this manoeuvre did not have a significant effect in normal subjects, or had a variable effect in the ST group. These results suggest that those with torticollis following VIII nerve lesions are a distinct group. Since there was no relationship between the side of the VIII nerve lesion and the direction of the torticollis a direct aetiological link between the two is, however, unlikely. The unusual EMG/tilt responses are explained on the basis of peripheral imbalance of utricular signals (maximal in the supine position) in the presence of central deranged processing of information concerning head posture.

Electromyography↗

Malignant angioendotheliosis involving the nervous system: support for a lymphoid origin of the neoplastic cells.

The clinical and post mortem findings of a case of malignant angioendotheliosis are described. The patient presented with neurological signs attributable to repeated episodes of cerebral and spinal cord infarction. Histological examination showed multifocal intravascular proliferation of mononuclear cells. Immunocytochemical characterisation of these neoplastic cells supports the recent suggestion that this disease represents an unusual form of intravascular lymphoma, which appears to show a predilection for blood vessels of the nervous system.

Antigens, Neoplasm↗

Effects of cyclosporin A on expression of IL-2 and IL-2 receptors in normal and multiple sclerosis patients.

The effects of the immunosuppressant Cyclosporin A (CsA) on T cell activation in vivo and in vitro were examined using the monoclonal antibody, anti-Tac, for interleukin 2 (IL-2) receptors and 3.9C2, for a peptide fragment of human IL-2. Peripheral blood lymphocytes (PBL) were stimulated with PHA in the presence of CsA. The expression of IL-2 receptors and production of IL-2 were reduced. PBL from CsA-treated MS patients had significantly lower proportions of Tac+ cells compared with untreated patients. This inhibition was not reflected in the CSF lymphocyte populations from CsA-treated patients and indicates the urgent need for an immunosuppressant drug which can enter the CNS in sufficient concentrations to inhibit local T cell activation.

Cyclosporins↗