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Biomedical subjects

D H Miller

Publications and source records attributed to D H Miller.

At least 361 records · Page 20Linked to original sources
PubMed1993

Gadolinium enhancement increases the sensitivity of MRI in detecting disease activity in multiple sclerosis.

There is now widespread agreement that serial brain MRI is useful in monitoring treatments designed to modify the course of multiple sclerosis. It has been less clear whether gadolinium enhancement is needed. We therefore compared the relative sensitivity of long repetition time (TR) spin echo (SE) and gadolinium enhanced short TR SE sequences in detecting active lesions. A blind analysis of the two sequences was performed in 26 untreated patients with early relapsing--remitting (19) or secondary progressive (seven) multiple sclerosis who underwent monthly MRI on four occasions (one baseline and three follow-up). Active lesions were defined as either new or enlarged lesions on long TR SE, or new or persistent enhancing lesions on short TR SE. In one patient there were 144 active lesions, all of which were seen with enhancement on short TR SE, but only 17 were seen on long TR SE. Amongst the remaining 25 cases, a total of 106 active lesions were seen: 68 (64%) were seen only with enhancement on short TR SE, 16 (15%) were seen only on long TR SE, while 22 (21%) were active on both sequences. We conclude that gadolinium enhancement markedly increases the sensitivity of monthly brain MRI in monitoring the treatment of relapsing--remitting or secondary progressive multiple sclerosis. With this frequency of scanning, a post contrast short TR SE sequence is the most sensitive method for detecting active lesions. The smaller yet still substantial incidence of active lesions seen only on the long TR SE sequence suggests that it should also be obtained.

Adult↗
PubMed1993

Cerebrospinal fluid kallikrein in spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats.

OBJECTIVE: To determine whether immunoreactive tissue kallikrein levels in cerebrospinal fluid (CSF) of spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)--salt-treated hypertensive rats are elevated compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats. DESIGN: The present study was designed to test the hypothesis that the activity of the brain tissue kallikrein-kinin system is enhanced in hypertensive states. METHODS: Age-matched 18- to 19-week-old SHR and WKY rats, and Sprague-Dawley rats treated for 6 weeks either with 2 mg/kg per day DOCA subcutaneously and 0.9% saline in the drinking water, or with vehicle and tap water to drink, were studied. CSF was collected from a cannula inserted into the cisterna magna, and was frozen until the tissue kallikrein in the samples was measured by radioimmunoassay. Arterial pressure in the SHR and WKY rats was measured directly via a cannula inserted in the femoral artery or by tail-cuff plethysmography. RESULTS: In adult 18- to 19-week-old SHR the CSF kallikrein concentration was higher than in WKY rats. The CSF flow rate in SHR was also higher than in WKY rats. The rate of appearance of kallikrein in the CSF of SHR was twice that in WKY rats. Moreover, CSF kininogenase activity in SHR was significantly higher than that in age-matched WKY rats. In DOCA--salt hypertensive rats the CSF kallikrein concentration was higher than in vehicle-treated control rats. Acute elevation of blood pressure with a 120-min intravenous phenylephrine infusion did not change the CSF kallikrein concentration in 50 rats compared with vehicle-treated control rats. This is the first study to quantitate immunoreactive tissue kallikrein in the CSF of rats and to show elevated levels of CSF kallikrein in hypertensive rats compared with normotensive rats. CONCLUSION: The present data suggest that higher brain kallikrein activity in hypertensive rats may play a role in the development of elevated blood pressure.

Animals↗
PubMed1993

Magnetic resonance imaging of the central nervous system in Behçet's disease.

Magnetic resonance imaging (MRI) was performed in 25 patients with Behçet's disease, of whom 15 had clinical involvement of the central nervous system (CNS). Brain MRI was abnormal in 11/15 with and in 1/10 without CNS involvement. The most common sites of MR lesions were the cerebral white matter and brainstem. Lesions were also seen in the basal ganglia, cerebellum, optic nerves and spinal cord. The cerebral white matter lesions were always asymptomatic and usually small, whereas the brainstem lesions were often symptomatic and sometimes extensive. Follow-up MRI in 2 patients presenting with brainstem syndromes and treated with immunosuppression showed resolution of a large lesion in 1 patient in whom there was clinical remission, and the development of marked brainstem atrophy in the other who became severely disabled. The pattern of MRI abnormalities may assist the diagnosis and suggests a role for MRI in monitoring the effect of treatment in patients with neurological Behçet's disease.

Adolescent↗
PubMed1993

Spinal cord MRI using multi-array coils and fast spin echo. I. Technical aspects and findings in healthy adults.

It is time-consuming to detect intrinsic spinal cord lesions in multiple sclerosis (MS) by MRI using conventional surface coils and T2-weighted spin-echo pulse sequences. Multi-array coils and fast spin-echo pulse sequences permit the generation of high-resolution T2-weighted sagittal images of the whole spinal cord in about 5 minutes. Using these advances, we found an area of high signal within the cord in only 1/45 (2%) healthy subjects aged 18 to 72 years, whereas 26% of those who underwent brain imaging had cerebral white matter abnormalities. Degenerative vertebral column changes, especially in the cervical region, were present in 64% and were associated with cord compression in 11%. Cord cross-sectional areas in mm2, measured from axial gradient-echo images, were usually highly reproducible and showed a significant correlation with the subject's height. We conclude that (1) MRI signal abnormalities within the spinal cord may be more specific for MS than cerebral white matter lesions, especially in subjects over 50 years old; (2) asymptomatic degenerative changes in the vertebral column are common, even in younger adults; (3) measurement of cord cross-sectional area should allow accurate quantitation of the degree of atrophy in MS and other spinal cord diseases; and (4) multi-array coils and fast spin echo represent an important advance in MRI of the spinal cord.

Adolescent↗
PubMed1993

Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis.

We performed MRI of brain and spinal cord on 80 patients with multiple sclerosis (MS). Using multi-array coils and fast spin echo, 139 intrinsic lesions were identified in 59 patients (74%). Lesions were more common in the cervical than in the thoracic cord. Cross-sectional areas of the cord, measured from axial images at four levels, showed atrophy in 40%. Clinical disability correlated with cord atrophy but not with cord lesion load. These results show that the use of multi-array coils and fast spin echo allows rapid and sensitive detection of spinal cord lesions in MS and that the cord is involved in the majority of patients. A lack of association between cord lesions and disability may relate to limitations in MR resolution but also suggests that the mechanisms of disability in MS are complex and multifactorial.

Adult↗
PubMed1992

Volume measurement of multiple sclerosis lesions with magnetic resonance images. A preliminary study.

The ability to visualise multiple sclerosis lesions in vivo with magnetic resonance imaging suggests an important role in monitoring the course of the disease. In order to help the long-term assessment of prospective treatments, a semi-automated technique for measuring lesion volume has been developed to provide a quantitative index of disease progression. Results are presented from a preliminary study with a single patient and compared to measurements taken from lesion outlines traced by a neuroradiologist, two neurologists and a technician. The semi-automated technique achieved a precision of 6% compared to a range of 12-33% for the manual tracing method. It also reduced the human interaction time from at least 60 min to 15 min.

Brain↗
PubMed1992

Gadolinium-enhanced magnetic resonance imaging of the central nervous system in systemic lupus erythematosus.

Gadolinium (Gd)-DTPA enhanced magnetic resonance imaging (MRI) was performed in 15 systemic lupus erythematosus patients with past (12) or present (3) features suggesting central nervous system (CNS) involvement. Symptomatic Gd-DTPA enhancing lesions were seen in 2 patients, and immunosuppressive treatment was associated with a rapid reversal of enhancement. The pattern of enhancement was different from that usually seen in multiple sclerosis. Gd-DTPA enhanced MRI may sometimes be useful in demonstrating the activity of CNS lupus.

Adolescent↗
PubMed1992

Occurrence of a multiple sclerosis-like illness in women who have a Leber's hereditary optic neuropathy mitochondrial DNA mutation.

Eight women are described who presented with bilateral, usually sequential, optic neuropathy, six of whom later developed a neurological syndrome indistinguishable from multiple sclerosis (MS). Magnetic resonance imaging, performed in five of the patients with an MS-like illness and in the two others with optic neuropathy alone, showed widespread white matter lesions as seen in MS. All of these women had matrilineal relatives with Leber's hereditary optic neuropathy, although this was not always apparent at presentation, and the most common mitochondrial DNA mutation associated with this disorder was detected in each of the women and their affected relatives. On the basis of observations made in these patients, the clinical features of Leber's hereditary optic neuropathy in males, and evidence for mitochondrially encoded peptides involved in the immune response in rodents, we propose that optic nerve damage in this disease could be immunologically mediated and that mitochondrial genes may contribute to susceptibility to MS.

Adult↗
PubMed1992

The pathological evolution of multiple sclerosis.

The new technique of nuclear magnetic resonance imaging (NMR) has been found to have particular value in the study of the evolution of the plaque of multiple sclerosis. Particularly when combined with gadolinium enhancement, the method not only shows very dramatically the waxing and waning of the plaque with time, it also demonstrates with remarkable clarity the important role of changes in vascular permeability in the pathological process. In this Annotation the ability of this technique to throw new light on the process of plaque formation and evaluation is critically assessed. In addition, the role of changing fluid content of the extracellular spaces of the CNS in influencing interpretation of the more conventional clinical and electrophysiological findings is discussed. While the method of NMR analysis does not yet show us how the plaque is initiated, it is suggested that future studies with these new techniques in the living subject may well lead us to rational therapeutic approaches based on pathogenetic mechanisms.

Humans↗
PubMed1992

Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric, and MRI follow up study.

There is a dearth of longitudinal studies on psychometric and psychiatric change in multiple sclerosis (MS) particularly on the evolution of these abnormalities early in the disease process. A 4 1/2 year follow up study documenting magnetic resonance imaging (MRI), psychometric, and psychiatric abnormalities was undertaken in a group of 48 patients with clinically isolated lesions--for example, optic neuritis--which are frequently the harbinger of MS. At follow up about half the subjects had developed clinically definite MS, with memory deficits becoming apparent. Deficits in attention documented at initial assessment were present but unchanged in those subjects who still had a clinically isolated lesion status. However, after MS was categorised into a relapsing-remitting or chronic progressive course, patients with a chronic progressive course were found to have significantly deteriorated with regard to auditory attention tasks. T1 relaxation times in apparently normal white matter correlated with certain indices of cognitive impairment. In developing a model to explain the pathogenesis of intellectual and emotional change in MS, the interaction of organic, psychological, and social factors needs to be emphasised.

Adult↗
PubMed1992

Propriospinal myoclonus in multiple sclerosis.

The clinical and electrophysiological features of segmental myoclonus affecting the right arm and upper trunk are described in a patient with multiple sclerosis. Electrophysiological studies suggested that the myoclonus was propagated from a generator site in the cervical cord, where lesions were found using MRI. The spread of electromyographic activity in each myoclonic jerk was slow and variable. These findings are characteristic of propriospinal myoclonus, which has not been associated with multiple sclerosis previously.

Adult↗
PubMed1992

The natural history of multiple sclerosis: a regional study with some longitudinal data.

A regional survey of multiple sclerosis (MS) patients in Wellington, New Zealand in 1983 identified 245 patients, giving a prevalence (all categories included) of 72 per 100,000. Retrospective review of the history and medical records identified a poorer prognosis for disability where there was progressive onset of symptoms, secondary progression after a remitting phase, older age of onset (40 years or more), or a motor syndrome involving the limbs at presentation. In 1983 follow up data were obtained on 96 patients who were seen during a previous survey in 1968. For those with definite or probable MS, progression to severe disability (Kurtzke disability status scale (DSS) 6-9) or death (DSS 10) was seen in 26/34 with moderate disability (DSS 3-5) in 1968 and in only 5/29 with mild disability (DSS 0-2). When the analysis is confined to those with symptoms for at least five years in 1968, severe disability or death from MS occurred in 22/30 with moderate and 4/19 with mild disability (chi 2 = 10.8, p = 0.001). It is concluded that the patient's established disability level after five years of illness is a useful, but not infallible, prognostic indicator. From the follow up of the 1968 patients, the probability of MS-related mortality for a given disease duration was calculated. Using this survival distribution to adjust the disability ratings in the 1983 population, it was found that the proportion with mild disability decreased steadily with increasing disease duration, reaching 14% when the disease duration was more than 25 years.

Adolescent↗
PubMed1992

High dose steroids in acute relapses of multiple sclerosis: MRI evidence for a possible mechanism of therapeutic effect.

The integrity of the blood-brain barrier (BBB) in multiple sclerosis (MS) was monitored by serial gadolinium-(Gd)-DTPA enhanced MRI during and after the treatment of acute relapses with a three day course of high dose intravenous methylprednisolone (IVMP). During treatment there was a rapid reduction of BBB abnormalities in 96% of enhancing lesions. In spite of sustained clinical improvement, many lesions re-enhanced within a few days of stopping IVMP, and new lesions frequently appeared within one month. It is possible that the rapid, albeit transient, reversal of BBB abnormalities contributes to the accelerated recovery from relapses associated with IVMP treatment.

Adult↗
PubMed1992

Symptomatic retrochiasmal lesions in multiple sclerosis: clinical features, visual evoked potentials, and magnetic resonance imaging.

We have studied 18 patients with relapsing-remitting multiple sclerosis (MS) who had symptomatic visual field defects due to retrochiasmal lesions. In 17, the lesion responsible was identified by magnetic resonance imaging (MRI), computed x-ray tomography (CT), or both. The lesion responsible involved the posterior optic radiations in eight cases, the optic tract and lateral geniculate nucleus in six, and the posterior limb of the internal capsule in three. The prognosis for recovery of the field defect was good; complete recovery occurred in 14 patients, and only two showed no recovery at all. The striking characteristic of the lesions was that most were unusually large; indeed, many were detectable on CT as well as MRI. Half-field asymmetries of either amplitude or latency of the visual evoked potentials (VEPs), consistent with a postchiasmal lesion, were present in only five out of 13 patients acutely. In only three of these did the abnormality persist at follow-up. We conclude that only large postchiasmal lesions are likely to cause symptomatic homonymous field defects in MS, usually characterized by rapid recovery. Hemifield VEPs have a low sensitivity for the detection of postchiasmal as compared with prechiasmal abnormalities.

Adult↗
PubMed1992

Frequent involvement of the optic radiation in patients with acute isolated optic neuritis.

Magnetic resonance imaging revealed asymptomatic lesions in white matter regions corresponding with the optic radiations in 20 of 28 patients (71%) with clinically isolated optic neuritis. In contrast to the findings with symptomatic lesions, there was no relationship between the latency of the visual evoked potential and the presence of these asymptomatic posterior visual pathway lesions.

Acute Disease↗