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Biomedical subjects

P Rudge

Publications and source records attributed to P Rudge.

At least 19 recordsLinked to original sources
PubMed2003

Interferon beta in multiple sclerosis: experience in a British specialist multiple sclerosis centre.

BACKGROUND: The efficacy of interferon beta (IFN beta) is well established in relapsing-remitting multiple sclerosis (MS). However, the use of this drug in clinical practice is complex, especially because it is only partially effective, its long term efficacy and side effects are unknown, its efficacy may be abrogated by the development of neutralising antibodies, compliance is variable, and its cost effectiveness is controversial. OBJECTIVES AND METHODS: Analysis of a prospectively followed up series of 101 MS patients treated with IFN beta was undertaken to: (1) monitor the outcome of IFN beta treatment in clinical practice; (2) compare the immunogenicity of the three commercial IFN beta preparations available; (3) assess the proportion of patients fulfilling the current guidelines of the Association of British Neurologists for stopping IFN beta therapy. RESULTS: During a median treatment period of 26 months (range 2-85), the relapse rate decreased by 41%. Although the reduction in the relapse rate was similar for all three commercial products, none of the Avonex treated patients were relapse free, compared with 19% of the Betaferon treated and 27% of the Rebif treated patients (p=0.02). Neutralising antibodies were not detected in Avonex treated patients (0 of 18), compared with 12 of 32 (38%) Betaferon treated and 10 of 23 (44%) Rebif treated patients (p=0.02). Forty of 101 (40%) patients satisfied the current (2001) Association of British Neurologists criteria for stopping IFN beta treatment at some stage during their treatment. CONCLUSION: IFN beta is effective in reducing the relapse rate in patients with relapsing-remitting MS in routine clinical practice. However, after a median treatment duration of 26 months, 40% of initially relapsing-remitting MS patients seem to have ongoing disease activity, presenting as disabling relapses or insidious progression.

Adjuvants, Immunologic↗
PubMed2002

Positional down beating nystagmus in 50 patients: cerebellar disorders and possible anterior semicircular canalithiasis.

OBJECTIVES: To clarify the clinical significance of positional down beat nystagmus (pDBN). METHODS: A discussion of the neuro-otological findings in 50 consecutive patients with pDBN. RESULTS: In 38 patients there was evidence of CNS disease (central group) but in 12 there was not (idiopathic group). In the CNS group, presenting symptoms were gait, speech, and autonomic dysfunction whereas in the idiopathic group patients mostly reported positional vertigo. The main neurological and oculomotor signs in the CNS group were explained by cerebellar dysfunction, including 13 patients with multiple system atrophy. In patients with multiple system atrophy with a prominent extrapyramidal component, the presence of pDBN was helpful in the differential diagnosis of atypical parkinsonism. No patient with pDBN had the Arnold-Chiari malformation, a common cause of constant down beat nystagmus (DBN). In the idiopathic group, the pDBN had characteristics which suggested a peripheral labyrinthine disorder: vertigo, adaptation, and habituation. In six patients an additional torsional component was found (concurrently with the pDBN in three). Features unusual for peripheral disorder were: bilateral positive Dix-Hallpike manoeuvre in nine of 12 patients and selective provocation by the straight head-hanging manoeuvre in two. CONCLUSION: It is argued that some patients with idiopathic pDBN have benign paroxysmal positional vertigo (BPPV) with lithiasis of the anterior canal. The torsional component may be weak, because of the predominantly sagittal orientation of the anterior canal, and may not be readily seen clinically. Nystagmus provocation by bilateral Dix-Hallpike and straight head-hanging may be explained by the vertical upwards orientation of the ampullary segment of the anterior canal in the normal upright head position. Such orientation makes right-left specificity with the Dix-Hallpike manoeuvre less important than for posterior canal BPPV. This orientation requires a further downwards movement of the head, often achieved with the straight head-hanging position, to provoke migration of the canaliths. The straight head-hanging manoeuvre should be carried out in all patients with a history of positional vertigo and a negative Dix-Hallpike manoeuvre.

Adult↗
PubMed2001

Long-term retrograde amnesia...the crucial role of the hippocampus.

For patients with hippocampal pathology, disagreement exists in the literature over whether retrograde amnesia is temporally limited or very extensive depending on whether the anatomical damage is restricted to this structure or also involves additional temporal cortex. We report a comprehensive assessment of retrograde and anterograde memory functions of a severely global amnesic patient (VC). We found that he presented with a remarkably extensive and basically ungraded retrograde amnesia. This impairment profoundly affected four decades preceding the onset of his amnesia and encompassed both non personal and personal facts and events. VC also presented with a severe anterograde amnesia and a deficit in the acquisition of new semantic knowledge in the post-morbid period. Detailed MRI volumetric measurements revealed gross abnormalities in both hippocampi which were markedly shrunken. Of relevance to the debate on retrograde amnesia were the observations that the volumes of both entorhinal cortices and the remainder of both temporal lobes were normal. These data suggest that the hippocampus is critical not only for the efficient encoding and hence normal recall of new information but also for the recall of episodic information acquired before the onset of amnesia. Our results are compatible with the view that retrograde amnesia is both extensive and ungraded when the damage is limited to the hippocampus.

Aged↗
PubMed2001

The role of [18F]fluoro-2-deoxyglucose-PET scanning in the diagnosis of paraneoplastic neurological disorders.

The detection of an occult tumour in a patient with a suspected paraneoplastic neurological disorder (PND) may be difficult because of the limitations of conventional imaging techniques. [(18)F]fluoro-2-deoxyglucose-PET (FDG-PET) can visualize a small tumour anywhere within the body. We retrospectively reviewed the case notes of 43 unselected patients with suspected PND referred for FDG-PET scanning to determine how useful this technique was when conventional imaging was negative. All patients had undergone standard radiological investigations and bronchoscopy (where appropriate) prior to PET scanning. There were discrete areas of hypermetabolism suggestive of malignancy (positive) in 16 patients (37%). A tissue diagnosis of cancer was subsequently made in seven patients (two at post-mortem), further radiological studies were suggestive of cancer in one patient, one patient subsequently presented with a metastatic deposit which was biopsied, and four patients died shortly afterwards without a post-mortem. In three patients, subsequent investigations were negative for cancer. Serum anti-neuronal antibodies were present in 43% and CSF oligoclonal bands were present in 46% of patients with positive PET scans compared with 16 and 26%, respectively, in PET-negative patients, but this was not significant. Only one patient with a negative scan has been diagnosed subsequently as having malignancy on prolonged follow-up. These findings confirm that FDG-PET scanning is a useful technique in the detection of small tumours in patients with suspected PND. False positives and false negatives do occur, but at a sufficiently low frequency to justify the clinical usefulness of this technique.

Adult↗
PubMed2001

Visual vertigo: symptom assessment, spatial orientation and postural control.

Certain patients with balance disorders report a 'visual vertigo' in which their symptoms are provoked or aggravated by specific visual contexts (e.g. supermarkets, driving or movement of objects). In order to determine the causes of visual vertigo (VV), we assessed symptoms, anxiety and the influence of disorienting visual stimuli in 21 such patients. In 17 out of 21 patients, a peripheral vestibular disorder was diagnosed. Sixteen bilateral labyrinthine-defective subjects (LDS) and 25 normal subjects served as controls. Questionnaire assessment showed that the levels of trait anxiety and childhood motion sickness in the three subject groups were not significantly different. Reporting of autonomic symptoms and somatic anxiety was higher than normal in both patient groups but not significantly different between LDS and VV patients. Handicap levels were not different in the two patient groups, but the reporting of vestibular symptoms was higher in the VV than in the LDS group. The experimental stimuli required subjects to set the subjective visual vertical in three visual conditions: total darkness, in front of a tilted luminous frame (rod and frame test) and in front of a large disc rotating in the frontal plane (rod and disc test). Body sway was also measured in four visual conditions: eyes closed, eyes open, facing the tilted frame and during disc rotation. In psychophysical and postural tests, both LDS and VV patients showed: (i) a significant increase in the tilt of the visual vertical both with the static tilted frame and with the rotating disc; and (ii) an increased postural deviation whilst facing the tilted frame and the rotating disc. The ratio between sway path with eyes closed and eyes open (i.e. the stabilizing effect of vision) was increased in the LDS, but not in VV patients, compared with normal subjects. In contrast, the ratio between sway path during disc rotation and sway path during eyes open (i.e. the destabilizing effect of a moving visual stimulus) was increased in the VV patients but not in LDS. Taken together, these data show that VV patients have abnormally large perceptual and postural responses to disorienting visual environments. VV is not related to trait anxiety or a past history of motion sickness. The results indicate that VV emerges in vestibular patients if they have increased visual dependence and difficulty in resolving conflict between visual and vestibulo-proprioceptive inputs. It is argued that treating these patients with visual motion desensitization, e.g. repeated optokinetic stimulation, should be beneficial.

Adult↗
PubMed2001

Identification without naming: a functional neuroimaging study of an anomic patient.

The neural correlates of identification and name retrieval have proved difficult to characterise because both occur highly automatically in normal language processing. Thus, although some evidence points to the left anterior temporal cortex (ATC) as a brain region underlying these functions, its relative role in semantic and lexical retrieval processes is still a matter of debate. Positron emission tomography (PET) was used to measure regional cerebral blood flow responses to famous and non-famous visually presented faces and buildings in a severely anomic patient and in six control subjects, while they were performing a same-different matching task. Because the patient was able to identify the stimuli that he could not name, it was possible to investigate whether the left ATC would respond when identification occurred without name retrieval. Both the patient and the controls activated the left ATC when famous stimuli were compared with non-famous stimuli. This result supports the hypothesis of a predominantly semantic function of the left ATC.

Adult↗
PubMed2001

Paroxysmal alternating skew deviation and nystagmus after partial destruction of the uvula.

A patient with suspected brain stem glioma involving the area of the left vestibular nuclei and cerebellar peduncle, developed paroxysmal alternating skew deviation and direction changing nystagmus after biopsy of the inferior cerebellar vermis resulting in destruction of the uvula. Between attacks she had right over left skew deviation with asymptomatic right beating horizontal nystagmus. Slow phases of the resting nystagmus showed increasing velocity, similar to congenital nystagmus. At intervals of 40-50 seconds, paroxysmal reversal of her skew deviation occurred, accompanied by violent left beating horizontal torsional nystagmus lasting 10-12 seconds and causing severe oscillopsia. It is proposed that this complex paroxysmal eye movement disorder results from (1) a lesion in the left vestibular nuclei causing right over left skew and right beating resting nystagmus and (2) a disruption of cerebellar inhibition of vestibular nuclei, causing alternating activity in the vestibular system with intermittent reversal of the skew deviation and paroxysmal nystagmus towards the side of the lesion.

Adult↗
PubMed2000

The effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in multiple sclerosis.

We investigated the effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in patients with multiple sclerosis. Following a double blind trial designed to compare the effect of oral and intravenous methylprednisolone treatment on promoting recovery from acute relapses of multiple sclerosis, 80 patients were followed for two years with six-monthly assessments during which all subsequent relapses were recorded. The annual relapse rate was slightly higher in the oral compared with the intravenous methylprednisolone-treated patients (1.06 vs. 0.78), but the adjusted difference between the two groups was not statistically significant (0.18; 95% CI -0.19 to 0.55, P=0.3). The time to onset and the severity of the first relapse after treatment, the number of relapse free patients at the end of the follow-up period, and the severity of the relapses during the follow-up period were similar in the two groups. This trial did not show a statistically significant difference in relapse rate during the first two years following oral compared with intravenous methylprednisolone treatment.

Administration, Oral↗
PubMed1999

Oligodendroglial gliomatosis cerebri: (1)H-MRS suggests elevated glycine/inositol levels.

Oligodendroglial gliomatosis cerebri is very rare. We describe 42-year-old woman who had low-grade oligodendroglial gliomatosis cerebri confirmed on stereotactic biopsy. The diffuse nature of the tumour was apparent clinically, neurophysiologically, on MRI and on proton magnetic resonance spectroscopy (MRS). She also had an isolated, false-localising partial seventh nerve palsy. MRS, of which there are no previous reports, suggested elevated glycine/inositol levels. This might be explained by the cell lineage from which the tumour arose.

Adult↗
PubMed1999

Neurological complications in Behçet's syndrome.

The neurological complications of Behçet's syndrome have not been characterized with clarity. We present the clinical features, imaging characteristics and CSF findings of a series of 50 patients seen at the National Hospital for Neurology and Neurosurgery over the past 10 years. In this series, vascular complications had a low prevalence, whereas involvement of the brainstem was common; spinal cord lesions, hemisphere lesions and meningoencephalitis also occurred. Optic neuropathy, vestibulocochlear and peripheral nerve involvement occurred, but were rare. The prognosis for recovery was in general good, and the majority of those followed-up over a median of 3 years (range 1-19 years) had only single attacks. One-third of patients underwent further attacks, and four underwent progressive deterioration leading to disability. Factors suggesting a poor prognosis are repeated attacks, incomplete recovery, progressive disease course and a high level of CSF leucocytosis during acute attack. These data should be of help in the further definition of the clinical characteristics of this rare neurological disorder and in the planning of treatment trials.

Adult↗
PubMed1999

Effect of lamivudine on human T-cell leukemia virus type 1 (HTLV-1) DNA copy number, T-cell phenotype, and anti-tax cytotoxic T-cell frequency in patients with HTLV-1-associated myelopathy.

Patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) typically have a high HTLV-1 proviral load in peripheral blood mononuclear cells and abundant, activated HTLV-1-specific cytotoxic T lymphocytes (CTLs). No effective treatment for HAM/TSP has been described so far. We report a 10-fold reduction in viral DNA for five patients with HAM/TSP during treatment with the reverse transcriptase inhibitor lamivudine. In one patient with recent-onset HAM/TSP, the reduction in viral DNA was associated with a fall in the frequency of CTLs specific to two peptides in the immunodominant viral antigen Tax. The half-life of peripheral blood mononuclear cell populations was estimated from changes in viral DNA copy number, CTL frequency, reduction in CD25 expression, and the loss of dicentric chromosomes following radiation-induced damage. Each of these four different techniques indicated a cellular half-life of approximately 3 days consistent with continuous lymphocyte replication and destruction. These results indicate that viral replication through reverse transcription significantly contributes to the maintenance of HTLV-1 viral DNA load. The relative contribution of proliferation versus replication may vary between infected people.

Adult↗
PubMed1999

Spatz-Lindenberg disease: a rare cause of vascular dementia.

BACKGROUND: Isolated cerebral thromboangiitis obliterans (Spatz-Lindenberg disease) is not well recognized as a cause of vascular dementia. CASE DESCRIPTION: A 58-year-old woman presented with dementia and pyramidal signs. Neuroimaging showed multiple areas of white matter change. Brain biopsy showed intimal thickening of the walls of leptomeningeal and intraparenchymal arteries, almost to complete occlusion, with an intact internal elastic lamina and media and without inflammation or infiltration. The cortex showed only moderate gliosis. CONCLUSIONS: Spatz-Lindenberg disease should be considered in the differential diagnosis of vascular dementia. Additional studies of its pathogenesis are required to determine appropriate treatment.

Cerebrovascular Disorders↗
PubMed1998

HTLV-I associated primary CNS T-cell lymphoma.

Primary T-cell lymphoma of the central nervous system (CNS) is an extremely rare tumour. The Human T-cell lymphoma virus type 1 associated Adult T-cell lymphoma/leukaemia (ATLL) often involves the CNS during its course but disease limited to the CNS is exceptional. Using clinicopathological and molecular biological information we describe a case of primary CNS ATLL with infiltration of the brainstem associated with an atypical Herpes simplex encephalitis the distribution of which corresponded to that of the tumour. CNS involvement in ATLL is discussed.

Adult↗
PubMed1998

The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up.

A definitive diagnosis of multiple sclerosis cannot be made at presentation on patients with a clinically isolated syndrome of the optic nerve, spinal cord or brainstem suggestive of demyelination, as dissemination in time is not established. To determine the long-term risk of abnormalities on brain MRI for the development of multiple sclerosis and disability we performed a 10-year follow-up on 81 such patients who had T2-weighted brain MRI at presentation. Initial brain MRI was abnormal in 54 (67%). Follow up of those patients with an abnormal MRI revealed progression to clinically definite multiple sclerosis in 45 out of 54 (83%), of whom 11 (20%) had relapsing/remitting disease (EDSS > 3), 13 (24%) secondary progressive and 21 (39%) benign (relapsing/remitting with EDSS < or = 3) disease. For those with a normal MRI progression to clinically definite multiple sclerosis occurred in only three out of 27 (11%), all benign. There was a significant relationship between the number of lesions at presentation and both EDSS (r = 0.45, P < 0.001) and the type of disease at follow-up (P < 0.0001). Brain MRI at presentation with a clinically isolated syndrome is predictive of the long-term risk of subsequent development of multiple sclerosis, the type of disease and extent of disability.

Adolescent↗