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C H Polman

Publications and source records attributed to C H Polman.

At least 163 records · Page 9Linked to original sources
PubMed1995

Increased number of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of patients with multiple sclerosis.

Observations in experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis (MS), have indicated that a low activity of the hypothalamo-pituitary-adrenal (HPA) system is accompanied by a high susceptibility for EAE in rat strains and that elevated corticosteroid levels are necessary for spontaneous recovery from EAE. The HPA axis activity is regulated by both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Both types of neurons are localized in the paraventricular nucleus (PVN) of the hypothalamus. We determined the number of immunocytochemically identified CRH-immunoreactive (CRH-IR) and AVP-immunoreactive (AVP-IR) neurons in the PVN of the human hypothalamus of 8 MS patients, aged 34-63 years, and 8 age-matched control subjects without any primary neurological or psychiatric disorders, aged 30-59 years. In addition, the number of oxytocin (OXT) immunoreactive (OXT-IR) neurons was determined, since these neurons innervate brain stem nuclei and might thus be related to autonomic disturbances in MS. In MS the staining intensity for AVP was clearly lower and for OXT slightly lower. For CRH, the staining intensity was similar in both groups, and, moreover, in MS patients the number of CRH-IR cells in the PVN was found to be about 2.4 times higher than that in the control group. The number of OXT-IR or AVP-IR cells in the PVN of MS patients was not significantly different from that of the control group. Our results point to an activation of the neuroendocrine HPA axis which may be compatible with the idea that the HPA axis is involved in recovery from MS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Correlating MRI and clinical disease activity in multiple sclerosis: relevance of hypointense lesions on short-TR/short-TE (T1-weighted) spin-echo images.

Magnetic resonance imaging (MRI) is being used as an outcome criterion in therapeutic trials in multiple sclerosis (MS) on the assumption that it, as a sensitive marker of biologic disease activity, could serve as a surrogate marker of disability. We evaluated the relation between MRI findings and disability in a quantitative follow-up study of 48 MS patients. Median duration of follow-up was 24 months (range, 10 to 42 months). Computer-assisted volume measurements employing a seed-growing technique yielded a standard error of measurement of 0.275 cm2. The median total area of the hyperintense lesions on the initial T2-weighted images was 8.4 cm2. The median increase was 0.76 cm2/yr (9%). In a subgroup (n = 19) with short-TR/short-TE spin-echo (SE) images, we measured the hypointense lesion load. The median total area of the lesions at entry was 0.70 cm2, with a median increase of 0.28 cm2/yr (40%). The total area of the hyperintense lesions on the initial T2-weighted images showed a weak correlation with the Expanded Disability Status Scale score at entry (Spearman rank correlation coefficient [SRCC] = 0.30; 0.02 < p < 0.05). The increase in disability showed a positive correlation (SRCC = 0.19) with the increase in hyperintense lesion load on the T2-weighted SE images, but this correlation did not reach statistical significance (p = 0.09), probably because of lack of clinical progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Multiple sclerosis therapy. A practical guide.

A growing amount of evidence suggests that a disturbance of immunological function is of importance in the pathogenesis of multiple sclerosis. This is reflected in the drugs used to slow progression and to treat relapses. Immunosuppressive drugs such as azathioprine, cyclophosphamide and cyclosporin might have some potential to slow down progression of multiple sclerosis, but their use is limited by potentially serious adverse effects. Recently, it was shown that interferon-beta-1b can diminish the exacerbation rate in multiple sclerosis without leading to unacceptable adverse effects. Nevertheless, symptomatic treatment remains of crucial importance in the management of multiple sclerosis patients. Spasticity, depression, fatigue and urinary, paroxysmal and sensory symptoms can all be alleviated to some extent with pharmacological interventions, although rehabilitation procedures and psychosocial consultations are no less important. Further therapeutic approaches to multiple sclerosis will be directed at either the specificity of the immune response or the grade of activation of the immune response. Magnetic resonance imaging techniques will play an important role in the evaluation of efficacy of new therapeutic agents.

Adjuvants, Immunologic↗
PubMed1995

The effect of gadolinium on the sensitivity and specificity of MR in the initial diagnosis of multiple sclerosis.

PURPOSE: To determine whether gadolinium can improve the sensitivity and specificity of MR imaging for the initial diagnosis of multiple sclerosis. METHODS: Patients (n = 57) with neurologic symptoms suggesting multiple sclerosis were studied prospectively. MR imaging consisted of T2-weighted and gadolinium-enhanced T1-weighted spin-echo images. Lumbar puncture was performed for cerebrospinal fluid analysis in 34 patients. RESULTS: After imaging, 17 patients (35%) had clinically definite multiple sclerosis. Cerebrospinal fluid examination had a sensitivity of 69% and specificity of 38%. Using liberal criteria, the sensitivity of T2-weighted MR imaging was 94% and the specificity 55%; using more strict criteria, the specificity increased to 65% with a sensitivity of 88%. Gadopentetate dimeglumine enhancement increased the specificity further to 80% with a loss of sensitivity (59%). CONCLUSION: Gadolinium enhancement increases the specificity of MR imaging in the early diagnosis of multiple sclerosis.

Adult↗
PubMed1995

Interferon beta-1b in secondary progressive multiple sclerosis--outline of the clinical trial.

This manuscript describes the outline of a double-blind, placebo-controlled, (European), multicentre phase III study to evaluate the safety and efficacy of 8 MIU of interferon beta-Ib given subcutaneously every other day for 3 years in patients with secondary progressive multiple sclerosis. The primary efficacy variable of this trial is the time to confirmed neurological deterioration as documented by the Expanded Disability Status Scale. The essentials of the study design are presented, including the rationale for the performance of the study and the selection of both clinical and magnetic resonance imaging outcome parameters.

Adjuvants, Immunologic↗
PubMed1994

4-aminopyridine in the treatment of patients with multiple sclerosis. Long-term efficacy and safety.

OBJECTIVE: To study the long-term efficacy and safety of 4-aminopyridine in patients with multiple sclerosis. DESIGN: Case series, follow-up varying from 6 to 32 months. SETTING: University referral center. PATIENTS: Thirty-one patients with definite MS, 23 of them being exposed to long-term administration (6 to 32 months) of 4-aminopyridine, since they showed a favorable initial response to the drug. INTERVENTIONS: Long-term oral treatment with 4-aminopyridine in daily doses of up to 0.5 mg/kg of body weight. MAIN OUTCOME MEASURES: Neurologic functions and symptoms as reported by the patients; side effects. RESULTS: Twenty of 23 patients who showed a favorable initial response benefited from long-term administration. Ambulation and fatigue (each in 13 patients) and visual function (in five patients) were most frequently reported to be improved. Three major side effects did occur during a follow-up of 406 patient months: a generalized epileptic seizure in two patients and hepatitis in one. CONCLUSIONS: Although a substantial proportion of patients with multiple sclerosis seem to benefit from long-term administration of 4-aminopyridine, additional studies are needed to clarify the exact value of the drug.

4-Aminopyridine↗
PubMed1994

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.

4-Aminopyridine↗
PubMed1994

Functional defects in peripheral blood T cells of multiple sclerosis patients. Diminished in vitro responsiveness in accessory cell dependent activation systems.

Function and phenotype of peripheral blood (PB) T cells in multiple sclerosis (MS) patients were analyzed. In whole blood cultures, T cell proliferation of multiple sclerosis (MS) patients, using soluble CD3 mAb and CD2 mAb as stimulants, was reduced in comparison to healthy controls. A similar difference was seen when isolated PBMC were tested after stimulation with soluble CD3 mAb. However, in accessory cell-independent activation systems, i.e. after stimulation of PBMC with immobilized CD3 mAb or after co-stimulation with CD28 mAb, both patients and controls responded equally well. Phenotypical analysis of the circulating T cell population showed that there were no differences in the percentage of CD26+, 'memory' (CD45R0+) or 'effector' (CD4+CD45R0+CD27-) cells between MS patients and healthy controls. Finally, although MS patients did show an enhanced proportion of 'naive' (CD4+CD45RA+) T cells, this did not correlate with the observed functional defects.

Adult↗
PubMed1994

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.

Adrenocorticotropic Hormone↗
PubMed1994

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.

4-Aminopyridine↗
PubMed1994

Magnetic resonance evaluation of disease activity during pregnancy in multiple sclerosis.

We followed two women with MS during pregnancy by means of serial unenhanced MR imaging. On each follow-up image, we assessed the number of new or enlarging lesions. Both women showed a decrease in MR disease activity during the second half of pregnancy and a return of MR disease activity to prepregnancy levels in the first months postpartum. These findings support the view that pregnancy reduces disease activity in MS.

Adult↗
PubMed1994

The effects of 4-aminopyridine on cognitive function in patients with multiple sclerosis: a pilot study.

4-Aminopyridine (4-AP) has a favorable effect on the disability of certain patients with MS. We investigated the effect of 4-AP on neuropsychological performance in 20 MS patients using a randomized, double-blind, placebo-controlled, crossover design. Although there was a trend for improved performance with 4-AP for two of the tests, we could not demonstrate significant effects of 4-AP on cognitive function.

4-Aminopyridine↗
PubMed1993

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.

Acute Disease↗
PubMed1993

Fatigue, sleep disturbances and circadian rhythm in multiple sclerosis.

The aim of this study was to investigate whether fatigue and sleep disturbances in multiple sclerosis (MS) patients might be due to disrupted circadian sleep wake regulation. Actigraphy and a multiple sleep latency test (MSLT) were performed in 16 MS patients with both prominent sleep complaints and fatigue. Actigraphy scores did not differ from control values, whereas sleep onset latency values were altered in subgroups of MS patients. No evidence was found for a generalized circadian disturbance in MS patients.

Adult↗