Sulphonylurea hypoglycaemic agents.
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Biomedical subjects
Publications and source records attributed to A G Kermode.
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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.
Late radiation-associated neurological injury is a recognised and often fatal complication of therapeutic ionising radiation. This retrospective study outlines its highly variable presentation, radiological findings and prognosis over a 6 year period in a major teaching hospital.
Six cases of contrast neurotoxicity with cerebral visual disturbance following angiography are presented. The typical clinical features, putative mechanisms and usual outcome of this uncommon but distinctive syndrome are discussed.
In patients with primary and secondary progressive multiple sclerosis (MS), major differences in the pattern and extent of abnormality on cerebral magnetic resonance imaging (MRI) between the two groups have recently been demonstrated. In the present study, 24 patients, matched for age, sex, duration of disease, and disability, had serial gadolinium diethylenetriaminepentaacetic acid-enhanced MRI over a 6-month period. The 12 patients in the secondary progressive group had a total of 109 new lesions over this time (18.2 lesions per patient per year) and 87% of these enhanced. Enhancement also occurred within and at the edge of preexisting lesions. In contrast, only 20 new lesions were seen in the primary progressive group (3.3 lesions per patient per year) and only one of these enhanced. There was no difference in the degree of clinical deterioration between the two groups over the 6-month period. These findings may indicate a difference in the dynamics of disease activity between the two forms of progressive MS, particularly in relation to the inflammatory component of the lesions, and have important implications for the selection of patients and the monitoring of disease activity in therapeutic trials.
Leakage of Gd-DTPA through a defective blood-brain barrier is measured quantitatively using dynamic MRI scanning, in which repeated scans are made after a bolus injection. Image registration artifacts are minimized; a dose of 0.1 mM/kg and an IR sequence enable enhancement to be measured quantitatively. The triexponential enhancement curve is fitted to a theoretical model based on compartmental analysis. The transfer constant, or permeability surface area product per unit volume of tissue (k), and leakage space per unit volume of tissue (v1) are measured. Estimates for a quickly enhancing multiple sclerosis lesion are k = 0.050 min-1, v1 = 21%; for a slow one k = 0.013 min-1, v1 = 49%. This implies permeability in the range 4-17 x 10(-6) cm s-1, in broad agreement with other physiological methods. The method is noninvasive and can be used to make serial measurements in patients and in experimental animal models. The time course of pathological aspects of diseases with blood-brain barrier breakdown, such as multiple sclerosis, tumors, and infections (e.g., HIV) can be studied, along with their response to therapy. The measurements are of physiological variables and are therefore independent of imaging equipment and field.
Three cases are presented in which clinical and radiological features suggested the diagnosis of glioma but surgical biopsy revealed a demyelinating process, with tissue destruction and cyst formation in two. One patient had clinically definite multiple sclerosis. Two had probable acute disseminated encephalomyelitis. Treatment with high dose steroids is appropriate when there is clinical or investigative evidence to suggest the presence of demyelinating disease, before deciding on biopsy.
OBJECTIVE: To compare the abnormalities shown by magnetic resonance imaging of the brain in three clinically distinct groups of patients with multiple sclerosis, and to correlate the extent of abnormality with the degree of clinical disability in the three groups. DESIGN: All patients underwent magnetic resonance imaging and full neurological examination, and their disability was scored according to the expanded Kurtzke disability state scale. SETTING: National Hospital for Nervous Diseases (Multiple Sclerosis NMR Research Group). PATIENTS: Three groups of patients with confirmed multiple sclerosis were studied: 12 patients with minimal disability despite a long (greater than 10 years) duration of illness (benign multiple sclerosis), 16 who had developed progressive disability after a relapsing and remitting course (secondary progressive multiple sclerosis), and 13 who had had progressive disability from the onset of the disease (primary progressive multiple sclerosis). MAIN OUTCOME MEASURES: Number and size of lesions in 17 anatomically defined sites; total lesion load, estimated with an arbitrary scoring system weighted for the size of lesions; and disability score. RESULTS: Magnetic resonance imaging showed that all 41 patients had abnormalities. These were extensive in the groups with secondary progressive and benign disease compared with the group with primary progressive disease. The lesions in the patients with secondary progressive disease were larger and more confluent than those in the two other groups (p = 0.007). Most lesions (85%) in the patients with primary progressive disease were under 5 mm in diameter; this percentage was higher than that in the two other groups (p = 0.032). Consequently the patients with primary progressive disease had the lowest mean lesion load (36.7); that in the patients with benign disease was 52.7 and that in the patients with secondary progressive disease 64.6 (p = 0.05). No correlation existed between disability and total lesion load. The distribution of brain lesions and of detectable lesions of the spinal cord, and the frequency of cortical atrophy, were similar in all groups. CONCLUSIONS: No relation was found between the degree of clinical disability and the extent of abnormality shown by magnetic resonance imaging: patients with clinically benign disease often had extensive abnormalities and those with primary progressive disease had surprisingly few lesions. Though magnetic resonance imaging increases knowledge of the disease process in multiple sclerosis and is invaluable in diagnosis, it is not helpful in predicting disability in individual patients.
From an extensive serial magnetic resonance imaging (MRI) study in multiple sclerosis (MS) we have identified 4 cases in which disruption of the blood-brain barrier, as detected by gadolinium-DTPA enhancement, preceded other MRI abnormalities and in 1 case clinical evidence of the new lesion. This supports the view that a defect in the blood-brain barrier, and therefore inflammation, is an early and possibly crucial event in the pathogenesis of the new lesion in MS. These cases showed a marked discrepancy between MRI abnormality and symptoms. The mechanisms contributing to this disparity are discussed, and it is concluded that far from being surprising it is to be expected.
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In a consecutive series of 30 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) minor clinical evidence of CNS involvement was found in five. Cranial magnetic resonance imaging (MRI) was performed in 28 and revealed abnormalities consistent with demyelination in nine patients aged less than 50 years and abnormalities in five aged 50 years or over. Measurements of central motor conduction time (CMCT) were obtained in 18 and showed unilateral or bilateral abnormalities in six. It is concluded that subclinical evidence of central nervous system (CNS) involvement is common, at least in patients with CIDP in the United Kingdom, but that clinically evident signs of CNS disease are infrequent. The association of a multiple sclerosis-like syndrome with CIDP is rare.
We performed 15 dynamic gadolinium-DTPA (Gd-DTPA)-enhanced MRI studies in 8 patients with relapsing and remitting multiple sclerosis; 7 were follow-up studies. We measured the time course of enhancement in 102 enhancing lesions for up to 384 minutes, with rest breaks. Immediate postcontrast MRIs demonstrated many different patterns of enhancement. We observed both uniformly enhancing and ring enhancing lesions. The enhancing regions were often less extensive than the corresponding high signal on T2-weighted images. Three lesions were seen with Gd-DTPA but not on unenhanced scans; 1 was seen on unenhanced scans 10 days later, suggesting that blood-brain barrier disturbance may precede other MRI signs of MS lesions. Three months later, some high-signal areas on T2-weighted scans had decreased in size to resemble the areas previously outlined by Gd-DTPA. This technique provides useful information about the pathogenesis and behavior of MS lesions.
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A case of multiple sclerosis is described in which spasmodic torticollis occurred abruptly and abated after 1 year. Magnetic resonance imaging (MRI) demonstrated a lesion in the mesencephalon. Other symptoms and physical signs that developed at the same time as the spasmodic torticollis were compatible with the lesion that had not been present on MRI 18 months previously. There are very few reports of spasmodic torticollis due to an identified focal lesion; there is evidence from experimental work on animals that midbrain lesions may cause spasmodic torticollis but there has been no previous human example.
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Thirteen males with Leber's optic neuropathy had magnetic resonance imaging (MRI) of the brain, and in eight the optic nerves were imaged using STIR (Short Time Inversion Recovery) sequences. All optic nerve scans were abnormal. In seven with bilateral visual loss four showed bilateral increased optic nerve signal and three unilateral increase. The involvement was of the mid and posterior intra-orbital sections over three 5 mm slices or more with sparing of the anterior portion. One patient with unilateral visual loss had increased signal only on the affected side. Brain MRI was normal, in marked contrast to the findings in clinically isolated optic neuritis in which multiple white matter lesions are seen in the majority.