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Biomedical subjects

D H Miller

Publications and source records attributed to D H Miller.

At least 307 records · Page 17Linked to original sources
PubMed1996

Clinical, CSF, and MRI findings in Devic's neuromyelitis optica.

OBJECTIVES: Since Devic's original description of neuromyelitis optica in 1894 there has been much debate regarding its aetiology. A specific cause has been identified in a minority of cases but in most the question has arisen whether or not Devic's neuromyelitis optica is a variant of multiple sclerosis. This study was undertaken to help clarify this issue. METHODS: Neuromyelitis optica was defined as (1) a severe transverse myelitis; (2) an acute unilateral or bilateral optic neuropathy; (3) no clinical involvement beyond the spinal cord or optic nerves, and (4) a monophasic or multiphasic illness. The clinical and autoantibody status was documented. Patients underwent CSF examination and MRI of brain and spinal cord. RESULTS: Twelve patients, with a mean age of presentation of 35.1 years, were seen. Eleven were women; vision was reduced to counting fingers or worse in 10 patients and seven became confined to a wheelchair. Examination of CSF showed local synthesis of oligoclonal bands in only two patients and a neutrophil pleocytosis in two. A possible aetiology was identified in five: a specific connective tissue disorder (two), pulmonary tuberculosis (one), and possible acute disseminated encephalomyelitis (two). Six had non-specific increases in various autoantibodies. Eleven patients underwent MRI of the brain and spinal cord. In 10 there were diffuse abnormalities involving cervical and thoracic cords with extensive swelling in the acute phase. Brain MRI was normal in five; in five there were multiple deep white matter lesions, and one patient had minor age related changes. CONCLUSION: It is proposed that Devic's neuromyelitis optica is a distinctive disorder with some clinical, CSF, and MRI features different from those found in classic multiple sclerosis. In most cases a specific aetiology is not identified, but an immunological mechanism of tissue damage seems likely.

Adolescent↗
PubMed1996

Brain and spinal cord MRI in motor neuron disease.

Motor neuron disease causes widespread degeneration of motor neurons within both the brain and spinal cord. Brain and spinal cord MRI were performed in 11 patients with motor neuron disease, and in 17 controls. Symmetric areas of high signal within the corticospinal tracts were found in nine patients on T2 weighted spin echo (SE) or fast spin echo (FSE) images of the brain and in eight on T2 or T2* weighed images of the spinal cord. High signal within the posterior limbs of the internal capsules was also found in four controls; this finding in isolation is therefore not pathological. No controls had abnormalities within the spinal cord. Low signal within the motor cortex was found in 10 patients, but was also seen in six controls. Thus MRI often displays characteristic abnormalities within the corticospinal tracts in patients with motor neuron disease, and should be considered in the investigation of suspected cases.

Adult↗
PubMed1996

Guidelines for MRI monitoring of the treatment of multiple sclerosis: recommendations of the US Multiple Sclerosis Society's task force.

In relapsing-remitting and secondary progressive multiple sclerosis (MS), MRI activity on monthly brain scans is a sensitive primary outcome measure in short term exploratory treatment trials. Because conventional MRI findings have a limited correlation with disability, the primary outcome in definitive trials should be clinical, although MRI is useful in providing an index of pathological progression. In trials aimed at preventing evolution from a clinically isolated syndrome to MS, MRI findings should be used in the entry criteria. The likely pathological substrates of irreversible disability are demyelination and axonal loss. Putative MR markers for these pathologies appear to relate more closely to disability than conventional MRI findings. Further technical developments should lead to improved quantitation, pathological specificity and clinical correlations.

Clinical Trials as Topic↗
PubMed1996

A phase II trial of anti-CD4 antibodies in the treatment of multiple sclerosis.

In multiple sclerosis (MS) myelin damage is the result of a chronic inflammatory process mediated by CD4 positive T helper/effector cells. In experimental allergic encephalomyelitis (EAE), the animal model of MS, treatment with anti-CD4 antibodies can prevent the onset of disease. Natural history studies have demonstrated that gadolinium enhanced magnetic resonance imaging (MRI) of the brain is more sensitive and objective in assessing inflammatory disease activity in MS than clinical monitoring, so that less patients and shorter studies suffice to reach the same statistical power as compared to trials using clinical outcome parameters. In this paper we describe the design of an exploratory trial of chimeric monoclonal anti-CD4 antibodies in the treatment of MS. For this study we chose the number of active MS lesions on monthly gadolinium enhanced MRI scans as the primary outcome measure.

Adolescent↗
PubMed1996

Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis.

Although serial MRI studies of the brain in relapsing-remitting MS have demonstrated frequent asymptomatic disease activity, less is known about the spinal cord. We carried out monthly gadolinium-enhanced brain and spinal cord MRI scans over 1 year in 10 patients with relapsing-remitting MS. Six of the patients had a total of 11 clinical relapses, eight of which involved the spinal cord. A total of 167 active (enhancing or new nonenhancing) lesions in the brain and 19 in the spinal cord were present. Only one active brain lesion was symptomatic compares with six spinal cord lesions. Overall, one-third of new spinal cord lesions were symptomatic, and three-quarters of clinical spinal cord relapses were associated with a new MRI lesion in a location appropriate to the symptoms. Activity in both the spinal cord and brain was more common around the time of relapse. There was a strong association between the spinal cord and brain MRI activity. We did not detect progressive spinal cord atrophy from measurements of a spinal cord cross-sectional area. We conclude that, in relapsing-remitting MS, imaging of the brain alone will detect 90% of active lesions; spinal cord MRI using current technology will therefore provide only modest gains in treatment trials in which lesion activity is the primary outcome measure. The lack of ++progressive spinal cord atrophy in these patients, suggesting that significant axonal loss has not occurred, is in keeping with their good recovery after relapse. That brain and spinal cord lesions occur concurrently implies a systemic trigger for disease activity.

Adult↗
PubMed1996

Clinical and magnetic resonance imaging predictors of disability in primary and secondary progressive multiple sclerosis.

The role of magnetic resonance imaging (MRI) in predicting disability in multiple sclerosis (MS) remains unclear. In this study 21 patients with primary and secondary progressive MS were reviewed 5 years following a serial MRI study of 6 months duration. In the secondary progressive group (n = 11) there was a significant relationship between the occurrence of enhancing lesions and clinical relapses during the initial 6 months and increase in disability 5 years later. For both groups change in disability over the initial study period was predictive of outcome. These results suggest that the presence and frequency of gadolinium enhancement (a marker of inflammation) and changes in disability over a short period are predictive of future deterioration in progressive patients.

Adult↗
PubMed1995

Differentiation of multiple system atrophy from idiopathic Parkinson's disease using proton magnetic resonance spectroscopy.

Proton magnetic resonance spectroscopy, localized to the lentiform nucleus, was carried out in 7 patients with the pure or predominantly striatonigral variant (SND) of multiple system atrophy (MSA), 5 patients with the olivopontocerebellar variant of MSA, 9 patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD), and 9 healthy age-matched controls. The MSA group with predominantly striatonigral involvement showed a significant reduction in the N-acetylaspartate (NAA)/creatine ratio (median, 1.19; range, 0.96-2.0; p < 0.02) compared with the NAA/creatine ratio from the control group (median, 1.76; range, 1.61-2.0). In contrast, the IPD group had a normal NAA/creatine ratio (median, 1.82; range, 1.19-2.31; p > 0.05). The NAA/creatine ratio was markedly reduced in 6 of the SND patients and in only 1 IPD patient. The choline/creatine ratio was also significantly lower in the SND group (median, 1.02; range, 0.91-1.23; p < 0.04) compared with the control group (median, 1.22; range, 1.05-1.65). The IPD group showed a normal lentiform choline/creatine ratio (median, 1.13; range, 0.89-1.65; p = 0.25) compared with controls. The olivopontocerebellar group also showed a significant reduction in the NAA/creatine ratio from the lentiform nucleus (median, 1.47; range, 1.22-1.68; p < 0.01) compared with the controls as well as a nonsignificant reduction in the choline/creatine ratio (median, 0.93; range, 0.85-1.27; p < 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Proton magnetic resonance spectroscopy of systemic lupus erythematosus involving the central nervous system.

We examined 13 patients with neurological manifestations of systemic lupus erythematosus (SLE) based on previous and/or current neurological or psychotic episodes by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) together with psychiatric and cognitive assessment. MRI was abnormal in 7 patients, showing high signal lesions in the white matter and/or cerebral atrophy. Proton MRS centred on white matter lesions in 5 patients showed a reduction in the N-acetyl aspartate creatine ratio compared with normal appearing white matter in the SLE group and in 10 healthy controls. This pattern of abnormality does not allow differentiation of SLE lesions from the chronic plaques occurring in multiple sclerosis. There was a very high incidence of current psychiatric morbidity in the SLE group, namely in 12 of the 13 patients. There was no correlation between the presence of current psychiatric involvement and/or cognitive dysfunction and abnormalities detected with MRI or MRS.

Adult↗
PubMed1995

Cranial MRI in idiopathic retinal vasculitis.

Ten patients with clinically isolated idiopathic retinal vasculitis who had a positive family history for multiple sclerosis (MS) or positive typing for HLA B7 underwent magnetic resonance imaging (MRI) of brain and optic nerves in order to establish the frequency of clinically silent lesions. Brain MRI was normal in seven and abnormal in three: one had a single small white matter lesion, two had extensive white matter abnormalities resembling those seen in MS. In two patients a lesion was shown in the optic nerve. These findings suggest that a minority of patients with idiopathic retinal vasculitis have disseminated central nervous system lesions characteristic of MS, the frequency of such changes being less than in patients with isolated optic neuritis.

Adolescent↗
PubMed1995

Affinity of antigen-specific IgG distinguishes multiple sclerosis from encephalitis.

The characteristics of antigen-specific IgG in patients with multiple sclerosis and patients with encephalitis have been compared. Both groups of patients showed antigen-specific oligoclonal bands locally synthesised in the CSF. When the affinity distribution of the antigen-specific IgG was measured there was a marked difference between the two groups. Encephalitis patients had high affinity antibody against the causative antigen. This was consistent with the antibody undergoing affinity maturation as a result of the immune system fighting a primary infection. Multiple sclerosis patients lacked high affinity response. This lack of high affinity antibody was also seen in those encephalitis patients when antigens other than the causative antigen were studied.

Adolescent↗
PubMed1995

Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss.

Proton magnetic resonance spectroscopy (MRS) and MRI were carried out in 11 patients with multiple sclerosis who had clinical evidence of severe cerebellar involvement, 11 multiple sclerosis patients (of similar age and disease duration) who had minimal or no signs of cerebellar disease, eight patients with autosomal dominant cerebellar ataxia (ADCA) and 11 healthy controls. In all subjects MRS was localized to cerebellar white matter (volumes of interest 3-6 ml). Apparent metabolite concentrations were calculated using the fully relaxed water spectrum as an internal standard of reference. The patients also underwent MRI to assess cerebellar volume and (in the two multiple sclerosis groups) lesion volume within the posterior fossa. Magnetic resonance spectroscopy from cerebellar white matter showed a highly significant reduction in the concentration of N-acetyl groups (NA) [which consists predominantly of N-acetylaspartate (NAA), a neuronal marker] in the multiple sclerosis group with cerebellar deficit compared with the multiple sclerosis group with minimal or no signs of cerebellar involvement, and healthy controls. Follow-up MRS performed in six of the multiple sclerosis patients 9 months later showed no change in the median NA concentration. The ADCA group showed a significant reduction of NA from a region of cerebellar white matter and also a reduction in the concentration of choline-containing compounds. The multiple sclerosis group with severe cerebellar deficit and the ADCA group both had significant cerebellar atrophy (suggesting nerve cell body and axon loss) compared with the multiple sclerosis patients with minimal or no signs of cerebellar deficit and healthy controls. The multiple sclerosis patients with cerebellar deficit had a significantly greater lesion volume in the posterior fossa, although the proportion of the spectroscopic voxel occupied by lesions was small, suggesting that axonal loss from normal appearing white matter also contributes to the observed reduction in NA. These results support the hypothesis that axonal loss is important in the development of persistent clinical disability in multiple sclerosis.

Adult↗
PubMed1995

Intra- and inter-observer agreement of brain MRI lesion volume measurements in multiple sclerosis. A comparison of techniques.

The measurement of MRI lesion load in multiple sclerosis is increasingly being used to evaluate the natural history of the disease and to monitor the efficacy of treatments. If, as might occur in multicentre studies, lesion load is measured by several observers in different patients or by the same observer in serial scans, it would be necessary to utilize a technique which provides results with high inter- and intra-observer agreements. This study was performed to evaluate the intra- and inter-observer agreement of semi-automated lesion volume measurement using thresholding, and to compare them with those obtained using an arbitrary scoring system (ASS) and a quantitative manual tracing method (MTM). Brain MRIs were obtained for 20 clinically definite multiple sclerosis patients and were evaluated independently by three observers. The median intra- and inter-observer agreements were, respectively, 88.5% (range 69.0-96.8%) and 79.0% (range 73.3-98.3%) using the ASS, 95.0% (range 85.1-99.4%) and 93.4% (range 77.3-98.3%) for the MTM, 96.3% (range 94.2-98.9%) and 93.7% (range 83.8-98.3%) for the semi-automated technique. The intra- and inter-observer agreements for the semi-automated technique increased to 98.5% (range 96.3-99.8%) and 96.1% (range 90.5-98.6%) when a consensus in the choice of threshold for lesion segmentation was reached. The intra- and inter-observer agreements were significantly greater for the semi-automated method compared with both the arbitrary scoring and the MTMs. The intra-observer variability for the semi-automated technique was significantly lower (P < 0.0001) than the inter-observer variability obtained using the same technique. These data indicate that it is possible to obtain high intra- and inter-observer agreements using a semi-automatic thresholding technique to quantify lesion volumes in multiple sclerosis. The technique may prove useful in multicentre studies, in which a single observer is still preferable.

Brain↗
PubMed1995

Quantitative assessment of MRI lesion load in monitoring the evolution of multiple sclerosis.

In recent years, several segmentation techniques have been developed to quantify brain MRI lesion load in multiple sclerosis and are now being used increasingly for both evaluating the natural history of the disease and monitoring the efficacy of treatment. Such techniques have been applied extensively to conventional T2-weighted images; there is less experience to date with gadolinium-enhanced scans and newer MR parameters which are thought to reflect the more destructive aspects of the pathological process. Manual outlining of lesions on T2-weighted images is moderately accurate when performed by an experienced observer and has been validated in large clinical trials, but is very time consuming. Semi-automated intensity-based techniques appear to be more reproducible, but are still slow to perform. Faster techniques with higher reproducibility are still needed. The correlations between conventional T2 lesion load and clinical outcome is strong in patients seen at first presentation with clinically isolated syndromes suggestive of multiple sclerosis, but much weaker in established multiple sclerosis. The application of quantitative assessment of the MR parameters which are more specific for the disabling aspects of the pathological process (i.e. demyelination, axonal loss and spinal cord involvement) may improve the correlation with clinical status.

Brain↗
PubMed1995

Magnetic resonance imaging and spectroscopy in multiple sclerosis.

Stimulated by the impressive effect of interferon beta on magnetic resonance imaging-detected disease activity, the past year or so has seen a particular interest in the use of magnetic resonance imaging to monitor treatment. To be effective in this regard, there needs to be a high sensitivity and accuracy in detecting disease activity, and the imaging findings should be predictive of clinical outcome, especially disability. A number of approaches show promise as being more sensitive than the conventional T2-weighted sequence. Furthermore, conventional magnetic resonance imaging cannot identify demyelination and axonal loss, the pathological substrates of irreversible disability. Newer magnetic resonance imaging techniques may be more pathologically specific, for example magnetization transfer imaging and magnetic resonance imaging spectroscopy. Such techniques provide new insights into the pathophysiology of multiple sclerosis. Improved methods for examining the often disabling spinal cord lesions have also emerged.

Aspartic Acid↗
PubMed1995

Bilateral simultaneous optic neuropathy in adults: clinical, imaging, serological, and genetic studies.

To elucidate the cause(s) of acute or subacute bilateral simultaneous optic neuropathy (BSON) in adult life, a follow up study of 23 patients was performed with clinical assessment, brain MRI, HLA typing, and mitochondrial DNA analysis. The results of CSF electrophoresis were available from previous investigations in 11 patients. At follow up, five (22%) had developed clinically definite multiple sclerosis, four (17%) had mitochondrial DNA point mutations indicating a diagnosis of Leber's hereditary optic neuropathy (LHON). The remaining 14 patients (61%) still had clinically isolated BSON a mean of 50 months after the onset of visual symptoms: three of 14 (21%) had multiple MRI white matter lesions compatible with multiple sclerosis, three of 14 (21%) had the multiple sclerosis associated HLA-DR15/DQw6 haplotype, and one of seven tested had CSF oligoclonal IgG bands; in total only five (36%) had one or more of these risk factors. The low frequency of risk factors for the development of multiple sclerosis in these 14 patients suggests that few will develop multiple sclerosis with more prolonged follow up. It is concluded that: (a) about 20% of cases of BSON without affected relatives are due to LHON; (b) multiple sclerosis develops after BSON in at least 20% of cases, but the long term conversion rate is likely to be considerably less than the rate of over 70% seen after an episode of acute unilateral optic neuritis in adult life.

Adolescent↗