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Biomedical subjects

P Rudge

Publications and source records attributed to P Rudge.

At least 55 records · Page 3Linked to original sources
PubMed1995

Superficial siderosis of the central nervous system.

There have been 87 cases of superficial siderosis of the CNS reported in the world literature and 63 cases had developed the clinical syndrome with sufficient details to be reviewed. It is a distinct clinical syndrome characterized by sensorineural deafness (95%), cerebellar ataxia (88%) and pyramidal signs (76%). Other features include dementia (24%), bladder disturbance (24%), anosmia (at least 17%), aniscoria (at least 10%) and sensory signs (13%). Less frequent features are extra-ocular motor palsies, neck or backache, bilateral sciatica and lower motor neuron signs (5-10% each). Males are more often affected than females (3:1). The age of onset ranged from 14 to 77 years, age at death from 29 to 78 years and duration until death from 1 to 38 years excluding premature death due to the underlying cause or as a result of surgery. Up to 27% become bed bound at 1-37 years from the first symptom due to either cerebellar ataxia, a myelopathic syndrome or both. Symptomatic subarachnoid haemorrhage occurred in 37% and the CSF was haemorrhagic and/or xanthochromic in 75%. It is now accepted that superficial siderosis is due to chronic subarachnoid haemorrhage and a source of bleeding has been reported in 54% of cases; it was either due to dural pathology (47%) including a CSF cavity lesion or cervical root lesion, a vascular tumour (35%) or a vascular abnormality (18%). Arguments are presented that the remaining cases were also due to chronic haemorrhage and that there is no evidence for a non-haemorrhagic form of superficial siderosis. There have been 14 incidental cases diagnosed by MRI or at post-mortem with no symptoms attributable to superficial siderosis during life, supporting the notion of a pre-symptomatic phase to the illness. In 22 patients who had developed the syndrome, the duration of this pre-symptomatic phase could be calculated and ranged from 4 months to 30 years with an average of 15 years. At present the most promising treatment for superficial siderosis is surgical ablation of the bleeding sources.

Adolescent↗
PubMed1995

Outcomes assessment in multiple sclerosis clinical trials: a critical analysis.

The feasibility and precision of clinical trials for the treatment of MS must be improved. Subsequent to the approval by the Food and Drug Administration of the United States of interferon beta-Ib as a safe and effective, though not curative, treatment for relapsing-remitting MS, the testing of other agents in this disease has been undertaken or is anticipated. This report summarises the discussions and recommendations of an international workshop held to review critically the elements of current MS therapeutic trials and to identify the most important aspects of clinical evaluation, study design and data analysis that would allow agents for MS to be tested as accurately, rapidly and economically as possible. While acknowledging the many uncertainties about the pathophysiology and natural history of MS, the workshop participants made recommendations about the preferred components to be used in the design of trials which may be different depending on the treatment goal and agent studied. It was concluded that the formulation of a useful clinical trial design must be based on specific guidelines for clinical scales and imaging for which task forces were recommended and subsequently appointed.

Clinical Trials as Topic↗
PubMed1995

Bilateral loss of vestibular function.

The clinical findings in 53 patients with bilateral vestibular failure (BVF) seen in a neurological hospital are reported. Bilateral acoustic neuromas were excluded. Seven patients (13%) had progressive cerebellar degeneration; these patients had no hearing complaints but showed gait ataxia, abnormal eye movements and cerebellar atrophy on neuro-imaging. Referral in these patients was primarily for eye movement assessment, and BVF was usually unsuspected. Neuropathies were present in 5 patients (9%), usually with normal central (brainstem-cerebellar) ocular motor function and variable patterns of hearing loss. The single largest group was idiopathic BVF (11 patients, 21%), patients presenting with vertiginous episodes, progressive unsteadiness or brief paroxysms of oscillopsia; auditory function, eye movements, neurological examination and imaging were usually normal. Nine patients (17%) suffered ototoxicity, mostly due to gentamicin; hearing was normal or mildly impaired. In 6 patients (11%) BVF was post-meningitic, with concomitant auditory loss. Autoimmune disease was found in 5 patients (9%); other organs were involved by the disease, and hearing was impaired but eye movements were spared. Miscellaneous neurological, otological or neoplastic diseases accounted for the remaining 10 patients. This study suggests that i) in patients with cerebellar degenerations, BVF may be underdiagnosed as the unsteadiness may be attributed only to the cerebellar disorder, ii) some patients with idiopathic BVF present with only minor visual or vestibular symptoms, and iii) detailed immunological screenings should be undertaken more often, in view of the significant proportion of patients with autoimmune and idiopathic BVF.

Caloric Tests↗
PubMed1995

Acquired pendular nystagmus: oculomotor and MRI findings.

The clinical, oculomotor and ophthalmological features of 27 patients with pendular nystagmus were studied in whom 22 also had MR imaging of the brainstem. The nystagmus was predominately horizontal in 4 patients, torsional in 5, vertical in 3 and mixed in trajectory in 8. Fifteen patients had conjugate nystagmus. Twelve patients had disconjugate nystagmus. Eight patients had INO. In 16 patients visual acuity was 6/12 or worse. Acuity and the presence of INO were unrelated to the conjugacy of the nystagmus. The MRI cuts at the medullary, pontine and midbrain levels were analysed statistically to determine the areas where there was significant (< 0.05%) overlap between areas of abnormal signal in different patients. Significant target areas for lesions causing the nystagmus were: in the pons the medial vestibular nucleus, central tegmental and paramedian tracts; in the medulla the inferior olivary nucleus, reticular formation, dorsal accessory olivary nucleus, central tegmental tracts and olivo-cerebellar fibres; in the midbrain the red nucleus and central tegmental tracts. Horizontal pendular nystagmus was preferentially associated with pontine lesions and torsional nystagmus with medullary lesions. Patients with conjugate nystagmus had a tendency to have bilateral mirror image MRI lesions (p = 0.028). The prevalence of lesions in our patients raises a possibility that more than one neuronal mechanism must be affected to produce pendular nystagmus. The inferior olive may be responsible for the rhythm of ocular oscillation. The disruption of pathways proximal to the oculomotor nuclei may determine the instability in terms of individual eye movement.

Adult↗
PubMed1994

Interferon beta-1b.

Explore the source record for details and available documents.

Clinical Trials as Topic↗
PubMed1994

Vestibular, cervical and visual remembered saccades in Parkinson's disease.

In order to assess both vestibulo-cervical perception of head rotation and saccadic function in Parkinson's disease, 14 patients with idiopathic Parkinson's disease were subjected to discrete sigmoid-shaped rotational displacements whilst fixating a target aligned with primary gaze in an otherwise dark room. The rotational stimuli were applied to (i) the whole body (vestibular stimulus); (ii) the trunk whilst the head remained stationary in space (cervical stimulus); (iii) to the head alone whilst the trunk remained stationary (combined vestibular and cervical stimulus). The fixation target was then extinguished and the subjects had to estimate the angle travelled by the head or trunk with an ocular-pointing task using information from the preceding rotational stimulus (vestibular and cervical 'remembered' saccades). It was found that, although these saccades in Parkinson's disease patients were multiple-step and hypometric, the final position of the eyes matched the rotational stimulus as accurately as in normal subjects. A complementary experiment in six patients showed that visual remembered saccads were hypometric, but significantly less so than vestibular remembered saccades. It is concluded that (i) vestibular and cervical perception of head/neck rotation is normal in Parkinson's disease; (ii) abnormalities of 'remembered' saccades, previously reported in Parkinson's disease, are not confined to the visual modality but involve other sensory modalities as well; (iii) across different modalities of memory-guided saccades, visual input improves saccadic performance. This result demonstrates that the known increased visual dependence found in Parkinson's disease extends to memory-driven tasks.

Adult↗
PubMed1994

Visually and memory guided saccades in a case of cerebellar saccadic dysmetria.

Saccades under four specific test conditions (visually guided, visually remembered, vestibular remembered, and cervical remembered) were studied in a 38 year old man with ocular dysmetria due to an angioma of the dorsal cerebellar vermis. The aim of the study was to investigate if the saccadic disorder was specific to certain subsets of saccades elicited by different sensory modalities. The experiments showed that initial saccades were equally hypermetric in all four conditions and that final eye position was normal in all memory guided saccade tests. Eye movements differed after the initial saccade, however. Whereas corrective saccades were seen in most visually guided and visually remembered experiments, postsaccadic centripetal drifts were documented in non-visual (vestibular and cervical) remembered saccades. These results indicate that the cerebellar vermis modulates the amplitude of the initial saccade (pulse size of saccadic innervation) independently of the saccadic task. The finding that post-saccadic drift never occurred when saccades were programmed using visual positional information suggests that the dorsal vermis may participate in the process of pulse step integration of saccades elicited by memorised vestibulo-cervical information.

Adult↗
PubMed1994

Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis.

We performed semiautomated quantitative measurement of brain magnetic resonance imaging (MRI) abnormalities seen at presentation and at 5-year follow-up in 84 patients presenting with an acute clinically isolated syndrome of the optic nerves, brainstem, or spinal cord suggestive of multiple sclerosis (MS). At follow-up, 34 (40%) had developed clinically definite and four (5%) clinically probable MS. Patients who developed MS during follow-up had a higher lesion load at presentation than those who did not. There was a strong correlation of the MRI lesion load at presentation with both the increase in lesion load over the next 5 years and disability at follow-up. Increasing initial lesion load correlated with a decreasing time to development of MS clinically (r = -0.328, p < 0.05). At follow-up, disability and brain lesion load were strongly correlated in patients who had developed MS. These results establish that MRI at presentation with clinically isolated syndromes suggestive of MS is useful in predicting the subsequent clinical course and the development of new MRI lesions. This suggests that quantitative brain MRI will be helpful in selecting patients with early clinical MS for treatment trials and for subsequent monitoring of their response to treatment.

Adolescent↗
PubMed1993

Dendritic cells in HIV-1 and HTLV-1 infection.

Individuals with HIV-1 infection show two major immunological effects--the early persistent stimulation of immune responses (e.g. of CD8 cells and antibody production) and later catastrophic immunodeficiency. Peripheral blood dendritic cells (DC) become infected with HIV-1 and infected cells can stimulate responses to virus. By contrast infected DC show a reduced capacity to stimulate either primary or secondary responses to other antigens. We have proposed that the block, particularly in primary responses, may be instrumental in the development of immunodeficiency. In HTLV-1 infected patients with tropical spastic paraparesis (TSP) a major feature of disease is 'spontaneous' T cell proliferation thought to underlie development of inflammatory neurological disease. We have now shown that some DC in addition to T cells are infected in TSP and that DC stimulate the persistent T cell activity. Here we demonstrate this using cells from an informative family where the daughter was normal, the father an HTLV-1 seronegative carrier and the mother had TSP. DC from all individuals stimulated normal allogeneic T cells in a mixed leukocyte reaction (MLR) and T cells responded well to normal allogeneic DC. T cells from the daughter showed little stimulation with autologous DC, those from the father showed significant but low stimulation, and T cells from the TSP patient gave a response to autologous DC which exceeded that to allogeneic DC. Taken together, the studies of DC and both HIV-1 and HTLV-1 indicate that infection of DC may play a central role in development of T cell abnormalities in human retrovirus-induced diseases.

Carrier State↗
PubMed1993

Diagnosis of enterovirus brain disease in hypogammaglobulinemic patients by polymerase chain reaction.

CSF samples taken from three patients with primary hypogammaglobulinemia and chronic brain disease were positive for enterovirus RNA by use of a technique based on the polymerase chain reaction (PCR) to amplify viral genomic sequences. Repeated attempts to culture viruses from the CSF from these patients were unsuccessful, possibly because the patients were treated regularly with intravenous immunoglobulin, which may have contained enough specific antibody to partially neutralize the viruses. Our data suggest that enteroviruses are responsible for diverse CNS features in patients with primary hypogammaglobulinemia and that for these patients the diagnosis should be pursued using PCR technology.

Adult↗
PubMed1993

Dendritic cells infected in vitro with human T cell leukaemia/lymphoma virus type-1 (HTLV-1); enhanced lymphocytic proliferation and tropical spastic paraparesis.

Evidence supporting a role of the dendritic cell (DC) in stimulating autologous T cell activity in tropical spastic paraparesis (TSP) was sought by studies of cells taken from healthy volunteers and exposed to HTLV-1 in vitro. DC were co-cultured with an HTLV-1-producing cell line (MT-2) at 1:1 or 10:1 ratios. These DC stimulated high levels of proliferation in autologous T cells. This was similar to that seen in an autologous mixed leucocyte reaction (AMLR) using cells from TSP patients. The requirement for both DC and virus was confirmed, since neither DC co-cultured with uninfected MT-2 cells nor addition of infected MT-2 cells directly to T cells caused significant stimulation. DC exposed to the highest dose of HTLV-1 (1:1) for 24 h before addition of T cells caused strong stimulation that increased after 8 h but almost disappeared by 72 h. In situ hybridization showed that approximately 25% of DC became infected in cultured cells after preincubation for 24 h, and over 50% were infected with a 72-h preincubation. We suggest that infection of DC by HTLV-1 may be an initial step in altering the immune system in seronegative patients, and that persistent T cell stimulation in those with genetic susceptibility may underlie the production of neurological disease.

Aged↗