Biomedical subjects
B M Uitdehaag
Publications and source records attributed to B M Uitdehaag.
Visual activation patterns in patients with optic neuritis: an fMRI pilot study.
We studied the use of functional MRI (fMRI) with visual stimulation in nine patients with unilateral optic neuritis. Eight healthy subjects served as controls. Patients showed reduced activation upon stimulation of the affected eye, on average 33% (range 0 to 156%) of the average monocular activation in the control group. Decreased activation was also seen for the unaffected eye (61% of control values, range 3 to 133%). We conclude that fMRI with visual stimulation is feasible in patients with optic neuritis and deserves future study.
Ibuprofen does not suppress active multiple sclerosis lesions on gadolinium-enhanced MR images.
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Interleukin-2 therapy does not exacerbate multiple sclerosis.
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Single-dose gadolinium with magnetization transfer versus triple-dose gadolinium in the MR detection of multiple sclerosis lesions.
PURPOSE: To compare the efficacy of single-dose gadolinium with magnetization transfer contrast (MTC) with that of triple-dose gadolinium in detecting enhancing multiple sclerosis lesions. METHODS: Twenty-one patients with multiple sclerosis were examined with MR imaging first with 0.1 mmol/kg gadolinium (single dose) and then, after 24 to 72 hours, with 0.3 mmol/kg gadolinium (triple dose). T2-weighted fast spin-echo and T1-weighted spin-echo MR images with and without MTC were obtained before contrast administration followed by either T1-weighted spin-echo images with MTC (single dose) or conventional T1-weighted spin-echo images (triple dose), starting 5, 17, and 29 minutes after contrast administration. All images were evaluated in a blinded fashion and scored in random order by two readers. Outcome parameters included number of enhancing lesions, number of active MR examinations (those containing at least one enhancing lesion), contrast ratio (signal intensity of enhancing lesion divided by signal intensity of normal-appearing white matter), and size of enhancing lesions. RESULTS: Eighty-one percent more enhancing lesions and 49% more active MR examinations were detected when a triple dose of gadolinium was used as compared with a single dose. The level of agreement between readers as to the number of enhancing lesions was significantly higher for triple-dose than for single-dose gadolinium. With triple-dose gadolinium, contrast ratios and areas of enhancement increased by 10% and 33%, respectively. Delayed imaging increased the size of the lesion by 11% on single-dose MTC images and by 18% on triple-dose images. CONCLUSION: Triple-dose gadolinium is more effective (higher sensitivity and interobserver agreement) than single-dose gadolinium in combination with MTC in detecting enhancing multiple sclerosis lesions.
The effect of the 21-aminosteroid U74006F on the clinical course of acute experimental allergic encephalomyelitis.
We evaluated the clinical effect of several doses of the 21-aminosteroid U74006F in acute experimental autoimmune encephalomyelitis (EAE) and compared it with the administration of methylprednisolone (MP). There was no significant change in the clinical course of EAE with the dosages we used, whereas the effect of MP was unquestionably beneficial. Based on these results U74006F does not seem to be a promising drug for the treatment of exacerbations of multiple sclerosis.
4-Aminopyridine is superior to 3,4-diaminopyridine in the treatment of patients with multiple sclerosis.
OBJECTIVE: To compare the efficacy and toxicity of 4-aminopyridine and 3,4-diaminopyridine in patients with multiple sclerosis. DESIGN: Intervention study with a before-after design and a randomized, double-blind, crossover design. SETTING: University referral center. PATIENTS: Twenty-four patients with definite multiple sclerosis who had been treated in a previous clinical trial with 4-aminopyridine. INTERVENTIONS: Nonresponders to treatment with 4-aminopyridine (14 patients) were treated with 3,4-diaminopyridine in a 4-week, open-label trial with doses up to 1.0 mg/kg of body weight (before-after design). Responders to treatment with 4-aminopyridine (10 patients) participated in a comparative study of 6 weeks' duration with 4-aminopyridine and 3,4-diaminopyridine according to a randomized, double-blind, double-crossover design. MAIN OUTCOME MEASURES: Neurophysiologic variables for nonresponders, neurologic functions and symptoms on a visual analogue scale for responders, and side effects for both groups. RESULTS: Toxicity profiles of 4-aminopyridine and 3,4-diaminopyridine were different, and systemic tolerability was reduced for 3,4-diaminopyridine. 4-Aminopyridine was more effective than 3,4-diaminopyridine, especially for ambulation, fatigue, and overall daily functioning. CONCLUSION: Our data suggest that, concerning both efficacy and side effects, 4-aminopyridine is superior to 3,4-diaminopyridine in the treatment of patients with multiple sclerosis.
Therapeutic effect of the D2-dopamine agonist bromocriptine on acute and relapsing experimental allergic encephalomyelitis.
We examined the effect of bromocriptine (BCR) treatment on the duration and severity of neurological symptoms of acute experimental allergic encephalomyelitis (EAE), an animal model for demyelinating diseases, particularly multiple sclerosis. To mimic the clinical situation, BCR treatment was started after the onset of clinical signs. Furthermore, the effect of BCR treatment on the course of a chronic relapsing form of EAE was studied. BCR was injected at daily intervals in a dose that resulted in sustained suppression of plasma concentrations of prolactin, a pituitary hormone that plays a role in immunoregulation. In acute EAE, BCR therapy reduced both severity and duration of the clinical signs. In chronic relapsing EAE, BCR treatment did not affect the severity and duration of the first attack, but reduced the duration of the subsequent, second attack. Thus, BCR treatment improves the clinical course in animals with ongoing disease. These findings may have implications for the search for new therapeutic approaches in multiple sclerosis.
Effect of K+ channel blockers on the clinical course and histological features of experimental allergic encephalomyelitis.
INTRODUCTION: Beneficial clinical effects of 4-aminopyridine (4-AP) in multiple sclerosis (MS) have been reported. The use of 4-AP in MS is based upon its ability to facilitate conduction in axons blocked by demyelination. This improvement is due to blocking of potassium (K+) channels in these fibres. Because K+ channels also play an important role in immune mechanisms successful treatment with K+ channel blockers in neuroimmunological diseases may have several causes. Therefore it seems important to study effects of K+ channel blockers in animal models of autoimmune disease. MATERIAL & METHODS: We studied the effects of 4-AP and quinidine on actively induced acute experimental allergic encephalomyelitis (EAE) in Lewis rats. RESULTS: There was no effect on the incidence of the disease. The severity of the disease was also unchanged although the disease duration was slightly diminished in the treated groups. Immunohistological comparison between the animals of different groups showed no differences. CONCLUSION: We conclude that 4-AP and quinidine are not capable of significantly changing the clinical course of EAE.
The significance of in-situ Ia antigen expression in the pathogenesis of autoimmune central nervous system disease.
Major histocompatibility class II antigen (Ia) expression is thought to play an important role in the pathogenesis of autoimmune central nervous system (CNS) disease. It has been suggested that Ia expression within the CNS might be sufficient to induce experimental allergic encephalomyelitis (EAE). The expression of Ia antigen in the CNS was studied during the natural course of both acute and chronic relapsing EAE. We found that Ia expression in the CNS starts at a relatively late stage in the course of EAE and persists after the disappearance of the clinical signs. In order to further evaluate the functional significance of Ia expression on glial cells we also studied the effect of intraventricular administration of interferon-gamma. This caused widespread Ia expression within the CNS but no signs of autoimmune CNS disease. Based on these results and data from the literature, the role of local Ia expression in the CNS is reconsidered. In certain circumstances Ia expression may contribute to suppressive rather than enhancing effects on the immune response.
The therapeutic effect of bromocriptine on acute and chronic experimental allergic encephalomyelitis.
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Intracerebral haemorrhage in Sneddon's syndrome.
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A brain-stem lesion in the Miller Fisher syndrome demonstrated by CT and MRI.
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Serial quantitative MR assessment of optic neuritis in a case of neuromyelitis optica, using Gadolinium- "enhanced" STIR imaging.
A patient is presented with neuromyelitis optica. MR imaging, using a short inversion time inversion recovery (STIR) technique, clearly depicted the lesion in the left optic nerve. Subsequent serial STIR imaging, with and without Gadolinium-DTPA, allowed quantitative assessment of changes parallel to improved optic nerve function. STIR imaging is a sensitive technique to demonstrate optic nerve lesions, and enables quantitative assessment to be made of the effect of (steroid) medication.
Failure of sulfasalazine to influence experimental autoimmune encephalomyelitis.
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Finding suggest spondylodiscitis.
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Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages.
Almost 50% of the cells infiltrating the central nervous system (CNS) of animals with experimental allergic encephalomyelitis (EAE) are macrophages (M psi). To investigate the role of the M psi in the pathogenesis of EAE, we eliminated M psi by means of mannosylated liposomes containing dichloromethylene diphosphonate (Cl2MDP). Cl2MDP-containing liposomes injected intravenously eliminate M psi in spleen and liver. Incorporation of mannose into the lipid layers enables the liposomes to pass the blood-brain barrier (BBB). Injections of Cl2MDP-containing mannose liposomes intravenously shortly before the appearance of clinical signs, markedly suppressed the expression of clinical signs of EAE. This suppression was accompanied by a marked reduction of infiltrated M psi in the CNS. Cl2MDP-containing liposomes without mannose incorporated had no effect. Cl2MDP-containing mannosylated liposomes had no effect on plasma corticosterone levels compared with injections of saline; thus, the suppression of expression of EAE was not corticosterone mediated. These results show that the M psi within the CNS play an important role in the pathogenesis of EAE.
Suppression of experimental allergic encephalomyelitis by intraventricular administration of interferon-gamma in Lewis rats.
Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS) which causes paralysis. Several studies have reported the involvement of Ia antigen-expressing cells in the pathogenesis of EAE. Interferon-gamma (IFN-gamma) can induce Ia antigen expression on a wide range of cells. We examined the effect of IFN-gamma on EAE in Lewis rats. Systemically administered IFN-gamma did not change the disease course of EAE, whereas IFN-gamma applied locally into the ventricular system of the CNS resulted in complete suppression of clinical signs. Furthermore, we found that systemic administration of anti-IFN-gamma just prior to the onset of clinical symptoms resulted in a more severe disease course. We conclude that IFN-gamma is capable of exerting a suppressive action in EAE, possibly through induction of Ia antigen expression or through the induction of suppressive mechanisms locally in the CNS.