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Biomedical subjects

W I McDonald

Publications and source records attributed to W I McDonald.

At least 19 recordsLinked to original sources
PubMed1996

Lesion discrimination in optic neuritis using high-resolution fat-suppressed fast spin-echo MRI.

Fast spin-echo (FSE) is a new sequence with acquisition times currently down to one-sixteenth of those obtained with conventional spin-echo sequences, which allows high-resolution (512 x 512 matrix) images to be acquired in an acceptable time. We compared the higher resolution of FSE with the medium resolution of a short inversion-time inversion-recovery (STIR) sequence in depicting the optic nerves of healthy controls and patients with optic neuritis. Optic nerve MRI examinations were performed in 18 patients with optic neuritis and 10 normal controls. Two sequences were obtained coronally: fat-suppressed FSE (FSE TR 3250 ms/TEef 68 ms, echo-train length 16, 4 excitations, 24 cm rectangular field of view, 3 mm interleaved contiguous slices, in-plane resolution 0.5 x 0.5 mm) and STIR (TR 2000 ms/TE 50 ms/TI 175 ms, in-plane resolution 0.8 x 0.8 mm, slice thickness 5 mm). FSE demonstrated much more anatomical detail than STIR, e.g. distinction of optic nerve and sheath. Lesions were seen in 20 of 21 symptomatic nerves using FSE and in 18 of 21 using STIR. Nerve swelling or partial cross-sectional lesions of the optic nerve were each seen only on FSE in 3 cases. Fat-suppressed FSE imaging of the optic nerve improves anatomical definition and increases lesion detection in optic neuritis.

Adult↗
PubMed1996

Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression.

Recent MRI studies in multiple sclerosis have highlighted the potential importance of spinal cord atrophy (implicating axonal loss) in the development of disability. However, the techniques applied in these initial studies have poor reproducibility which limits their application in the serial monitoring of patients. The aim of this study was to develop a highly reproducible and accurate method for the quantification of atrophy. The technique we describe demonstrates an intra-observer coefficient of variation (scan-rescan) of only 0.8%. When applied to 60 patients with clinically definite multiple sclerosis there was a strong correlation between spinal cord area and disability measured by Kurtzke's Expanded Disability Status Scale (EDSS) (r = -0.7, P < 0.001). The correlation was graded providing evidence for a causal connection. At levels 3 and 8 of the EDSS we observed a reduction in average cord area of 12 and 35%, respectively. Given its reproducibility, the magnitude of the change detected and the strong correlation with disability, this new technique should prove to be a sensitive measure of progressive neurological deterioration and could be readily incorporated into imaging protocols aimed at monitoring therapy.

Adult↗
PubMed1996

Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI.

Although MRI detects the white matter lesions of multiple sclerosis within the brain with high sensitivity, a minority of patients have normal brain MRI. We describe 20 patients, selected from over 170 who had undergone brain imaging with minimal (n = 12) or no (n = 8) abnormalities (median number of lesions = I, range, 0-3) but in whom spinal MRI was abnormal. Twelve had clinically definite or laboratory supported definite multiple sclerosis according to the Poser criteria; one had clinically probable disease and seven, not fulfilling the Poser criteria, were classified as possible multiple sclerosis. All had presented with symptoms and signs referable to the spinal cord or optic nerves. Eleven had a primary progressive course, eight relapsing-remitting and only one secondary progressive. Moderate or severe disability was the rule in the primary progressive cases; all the relapsing-remitting patients had minimal disability. All had at least one lesion visible in the spinal cord (median 2; range 1-6). In patients in whom the diagnosis of multiple sclerosis is not supported by abnormalities on brain MRI, imaging of the spinal cord can be of considerable value.

Adult↗
PubMed1996

MRI dynamics of brain and spinal cord in progressive multiple sclerosis.

OBJECTIVE: To assess the usefulness of serial cord MRI in patients with progressive multiple sclerosis. METHODS: Monthly MRI of the brain and spinal cord with and without gadolinium enhancement was carried out in 19 patients with progressive multiple sclerosis (10 primary progressive, nine secondary progressive) over the course of one year. RESULTS: During this period there were 132 active lesions in the brain and only six in the cord. One hundred and twelve (85%) active brain lesions occurred in the secondary progressive group; three new cord lesions occurred in each group. In the secondary progressive group MRI activity was high in patients who had superimposed relapses, whereas in those who progressed without relapse and in the primary progressive group it was low. Cross sectional areas of the cord decreased at the C5 level in both groups, implying progressive atrophy of fibre tracts. There was no relation between either brain or cord MRI activity and change in disability over the study period. CONCLUSIONS: Although the detection of new lesions by frequent cord imaging using current technology has little role in the monitoring of disease activity in progressive multiple sclerosis, the serial measurement of cord cross sectional area may be important. There is also evidence to suggest that the mechanism underlying irreversible disability in patients with progressive multiple sclerosis may be different in patients who continue to relapse than in those who do not.

Atrophy↗
PubMed1996

A study of oligoclonal band negative multiple sclerosis.

OBJECTIVES: To determine whether oligoclonal band (OCB) negative multiple sclerosis is a reliable diagnosis and, if so, whether it has a distinctive prognosis. METHODS: Retrospective and matched prospective comparison of the clinical and laboratory features of patients with clinical definite multiple sclerosis with and without intrathecal synthesis of oligoclonal IgG. RESULTS: Thirty four patients were identified with apparent OCB negative clinically definite multiple sclerosis. The results of oligoclonal banding proved to have been equivocal in 14 of 34; the clinical diagnosis of multiple sclerosis was questionable in 8 of 34. The remaining 12 patients with "true" OCB negative multiple sclerosis were significantly less disabled than matched OCB positive controls. Re-examination of CSF-serum pairs from six OCB negative patients showed that three remained OCB negative while three showed evidence of intrathecal synthesis of OCBs. CONCLUSIONS: OCB negative clinically definite multiple sclerosis is rare and should be diagnosed with caution; in unequivocal cases it seems to have a relatively benign prognosis.

Adult↗
PubMed1996

A preliminary study into the sensitivity of disease activity detection by serial weekly magnetic resonance imaging in multiple sclerosis.

Long TR and gadolinium enhanced spin echo brain MRI was performed weekly for three months in three patients with relapsing-remitting or secondary progressive multiple sclerosis. During the study, 38 new enhancing lesions were seen; 11 showed enhancement for less than four weeks, and two enhanced on only one scan. All 16 new lesions seen on long TR scans showed initial enhancement. When only every fourth (monthly) scan was analysed, a total of 33 new enhancing lesions were seen. Subject to confirmation in a larger cohort, the results suggest: (a) that blood brain barrier leakage is an invariable event in new lesion development in relapsing-remitting and secondary progressive multiple sclerosis; (b) the small increase in sensitivity of weekly scanning does not justify its use in preference to monthly scanning when monitoring treatments.

Adult↗
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

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↗
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

High resolution proton NMR spectroscopy of multiple sclerosis lesions.

Tissue from postmortem multiple sclerosis and normal control brains was extracted with perchloric acid and analysed using proton NMR spectroscopy. The content of N-acetyl-derived groups (the sum of N-acetyl-aspartate, acetate, and N-acetylaspartylglutamate) was decreased in multiple sclerosis plaques compared with normal control white matter (mean, 4.36 vs. 6.64 mumol/g wet weight). In normal appearing white matter adjacent to plaques a corresponding decrease was seen, with no change in white matter distant from plaques. A decrease in the content of total creatine was observed in multiple sclerosis plaques in comparison with normal control white matter (mean, 4.64 vs. 6.56 mumol/g wet weight), which correlated strongly with the decrease in N-acetyl-derived groups. No changes in other metabolites such as total choline or myo-inositol were seen. The decreases in content of N-acetyl-derived groups are in agreement with observations from in vivo proton NMR spectroscopy in multiple sclerosis patients. The decrease in total creatine is in contrast to most of the observations made in vivo where total creatine is assumed to be unchanged and metabolite levels are often expressed as a total creatine ratio. The use of a total creatine ratio in vivo could lead to an underestimation of reductions in N-acetylaspartate and an apparent increase in other metabolites in the multiple sclerosis lesion.

Adult↗
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

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↗
PubMed1995

High resolution magnetic resonance imaging of the anterior visual pathway in patients with optic neuropathies using fast spin echo and phased array local coils.

High resolution MRI of the anterior visual pathways was evaluated using frequency selective fat suppressed fast spin echo (FSE) sequences in conjunction with phased array local coils in patients with optic neuropathies. Fifteen normal controls and 57 patients were examined. Coronal T2 weighted fat suppressed FSE images were obtained in 11 minutes with an in plane resolution of 0.39 x 0.39 mm. The optic nerve and its sheath containing CSF were clearly differentiated. Central retinal vessels were often visible. In demyelinating optic neuritis and in anterior ischaemic optic neuropathy high signal within the nerve was readily delineated. Meningiomas and gliomas involving the optic nerve were precisely visualised both in the orbit and intracranially. Extrinsic compression of the optic nerves was readily visualised in carotid artery ectasia and dysthyroid eye disease. Enlarged subarachnoid spaces around the optic nerves were demonstrated in benign intracranial hypertension. High resolution MRI of the anterior visual pathway represents an advance in the diagnosis and management of patients presenting with optic neuropathy.

Adult↗
PubMed1995

Signal intensity on MRI of basal ganglia in multiple sclerosis.

It has been reported that a relative reduction in signal intensity on T2 weighted MRI may be seen in the basal ganglia of patients with multiple sclerosis and furthermore that this is due to excessive iron deposition. The basal ganglia are, however, rarely involved clinically or pathologically in multiple sclerosis, casting some doubt on this finding. Therefore MRI was carried out in 46 patients with definite multiple sclerosis and 42 age matched controls. Contiguous, 5 mm thick axial dual echo spin-echo images of the brain were obtained on a 1.5T imager. Visual rating scales were used to measure the lesion load as well as the signal intensity of the globus pallidus, putamen, caudate nucleus, substantia nigra, red nucleus, and thalamus. There was a mild degree of low signal intensity in the patient group in the thalamus only. The signal intensity of the thalamus and putamen was never lower than that of the globus pallidus. Low signal in the basal ganglia is rarely, if ever, found in multiple sclerosis and is not a useful radiological sign.

Adolescent↗