Discrepancies in the interpretation of clinical symptoms and signs in the diagnosis of multiple sclerosis. A proposal for standardization.

The new McDonald diagnostic criteria for multiple sclerosis (MS) incorporate detailed criteria for the interpretation and classification of magnetic resonance imaging (MRI) findings, but, in contrast, provide no instructions for the interpretation of clinical findings. Because MS according to the McDonald criteria is one of the primary endpoints in a large trial enrolling patients after the first manifestation suggestive for a demyelinating disease (BENEFIT study), it was decided to organize a centralized eligibility assessment for this trial. During this eligibility assessment it was observed that there were marked inconsistencies in the decisions of participating neurologists with respect to the classification of clinical symptoms as being caused by one or more lesions provoking discussions in about one in every five patients.

Interferon beta-1b treatment does not induce autoantibodies.

Background: There is little information regarding the potential of interferon beta (IFNbeta) to induce or exacerbate autoimmune disease. Existing data from uncontrolled studies are contradictory and do not differentiate between autoimmune dysfunction, which is frequent in patients with multiple sclerosis (MS), and untoward drug effects.

Objective: To evaluate the impact of IFNbeta on hepatic, thyroid, and other markers of autoimmunity using data from the European placebo-controlled double-blind, multicenter study of IFNbeta-1b in patients with secondary progressive MS (SPMS).

Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology.

Background And Purpose: Cortical lesions constitute a substantial part of the total lesion load in multiple sclerosis (MS) brain. They have been related to neuropsychological deficits, epilepsy, and depression. However, the proportion of purely cortical lesions visible on MR images is unknown.

In vivo detection of myelin proteins in cervical lymph nodes of MS patients using ultrasound-guided fine-needle aspiration cytology.

Cervical lymph nodes (CLN) have been described to be the first lymphoid draining site of the brain. In this study we used ultrasound guided fine needle aspiration cytology (USgFNAC) to obtain cells, in vivo, from non-enlarged CLN of multiple sclerosis (MS) patients and HCs (HC), and investigated whether myelin proteins could be detected. Macrophages containing myelin basic protein (MBP) and proteolipid protein (PLP) were found in CLN of all MS patients, whereas these could only be detected in a minority of HC.

Multiple sclerosis diagnostic criteria: three years later.

New diagnostic criteria for multiple sclerosis (MS) were developed by an International Panel in 2001 and have had wide distribution and discussion since publication. These provided the first formal incorporation of magnetic resonance imaging (MRI) in a diagnosis work-up for patients suspected of having MS. The so-called McDonald criteria have been studied in retrospective and prospective analyses for sensitivity, specificity and utility, and have been proven to compare favourably or to be an improvement upon prior MS diagnostic criteria.

MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter.

Quantitative single-voxel, short echo-time (TE) MR spectroscopy (MRS) was used to determine metabolite concentrations in the cerebral normal-appearing white matter (NAWM) of 76 patients with multiple sclerosis (MS), and the WM of 25 controls. In NAWM of all MS disease types (primary progressive, relapsing-remitting, and secondary progressive), the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine (tCr) was decreased compared to controls. Remarkably, this was entirely due to an increase of tCr in MS patients, whereas there was no difference in tNAA.

Development of a cognitive behavioral group intervention programme for patients with multiple sclerosis: an exploratory study.

A substantial group of patients with multiple sclerosis (MS) has difficulty coping with their disease. Cognitive behavioral group interventions may help these patients cope more effectively with MS. We developed an 8-session group intervention programme for patients recently diagnosed with MS to help them cope more effectively with MS and to overcome negative thoughts and beliefs about the disease to improve health-related quality of life.

Axonal damage accumulates in the progressive phase of multiple sclerosis: three year follow up study.

Background: Neurofilament phosphoforms (Nf) are principal components of the axoskeleton released during axonal injury. Cerebrospinal fluid (CSF) levels of Nf phosphoforms might be useful surrogate markers for disability in multiple sclerosis (MS), aid in distinguishing clinical subtypes, and provide valuable prognostic information.

Method: Thirty four patients with MS were included in a three year follow up study along with 318 controls with other non-inflammatory neurological diseases.

[Medicinal cannabis for diseases of the nervous system: no convincing evidence of effectiveness].

--In 1996, the Netherlands Health Council issued a negative recommendation regarding the use of medication on the basis of cannabis (marihuana). However, interest in medicinal cannabis has certainly not waned since. --The neurological diseases for which cannabis could presently be used therapeutically are: multiple sclerosis, chronic (neuropathic) pain and the syndrome of Gilles de la Tourette.

Value of health-related quality of life to predict disability course in multiple sclerosis.

Objective: To determine the value of health-related quality of life (HRQoL) to predict change in disability status in patients with multiple sclerosis (MS).

Methods: Over a 5-year period, data were collected on HRQoL (Medical Outcomes Study Short Form-36 Health Survey) and disability status (Expanded Disability Status Scale) from a heterogeneous group of 81 Dutch-speaking patients with MS.

Results: Multivariate logistic regression analysis showed that HRQoL in the domains of Physical Functioning and Role-Physical Functioning is a significant predictor of change in disability status.

Expression of adhesion molecules on peripheral lymphocytes predicts future lesion development in MS.

The expression of adhesion molecules (alpha4beta1-integrin, LFA-1, ICAM-1) on T cells, measured by flow cytometry, was compared in different subtypes of multiple sclerosis (MS) and related to future lesion development as seen as delta T1 and T2 lesion load per year on magnetic resonance imaging (MRI). LFA-1 and alpha4beta1-integrin showed higher expression on CD4 and CD8 T lymphocytes in the secondary progressive compared to the relapsing-remitting (CD4: p<0.01, p=ns, p<0.

Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis.

Endogenous glucocorticoids (GC), which are under control of the hypothalamic-pituitary-adrenal axis, play an important role in controlling chronic inflammatory demyelinating diseases, like multiple sclerosis (MS). Increased hypothalamic-pituitary-adrenal axis activity has been found in MS patients and appeared to be negatively associated with acute inflammation. Exogenous GC are frequently used to treat relapses in MS, but the response to this treatment differs among patients, suggesting differences in sensitivity to GC.

Relation between objective and subjective measures of bladder dysfunction in multiple sclerosis.

The authors studied 297 patients with multiple sclerosis (MS), correlating urinary symptoms (bowel/bladder Functional System [FS] score of the Expanded Disability Status Scale [EDSS] and bladder dysfunction score of the Guy's Neurological Disability Scale [GNDS[) vs objective measurement of bladder dysfunction (postmicturition residual volume). EDSS and GNDS were of no value for predicting the presence of a clinically relevant postvoiding volume. Therefore, the authors recommend ultrasound scanning of residual volume in every patient with MS, even in the absence of subjective urinary symptoms.

CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis.

Objective: To investigate the relationship of CSF and the serum nitric oxide metabolites nitrite and nitrate (NOx) to disease activity and progression in patients with multiple sclerosis (MS).

Methods: The study was divided into cross-sectional and follow-up. In the cross-sectional study, 20 patients with relapsing-remitting (RR), 21 with secondary progressive (SP), and 10 with primary progressive (PP) MS and 14 control subjects were included.

Multiple Sclerosis Impact Scale (MSIS-29): relation to established measures of impairment and disability.

Objective: To validate the newly developed Multiple Sclerosis Impact Scale (MSIS-29) in a large, well characterized, independent group of MS patients by investigating the relation between the MSIS-29 and the Guy's Neurological Disability Scale (GNDS), the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC).

Methods: Two hundred MS patients were recruited at our outpatient department. At the same visit GNDS, EDSS, MSFC and MSIS-29 were assessed.

An fMRI study of planning-related brain activity in patients with moderately advanced multiple sclerosis.

Introduction: Cognitive impairment occurs in a substantial number of multiple sclerosis (MS) patients and often includes frontal lobe dysfunction. We used functional magnetic resonance imaging (fMRI) to study planning, an executive function, in moderately impaired MS patients.

Methods: An fMRI version of the Tower of London (ToL) test was used to study patterns of brain activation in 23 MS patients and 18 healthy controls.

Gender-related association between the TGFB1+869 polymorphism and multiple sclerosis.

Our objective was to investigate whether polymorphisms and haplotypes in the TGFB1 gene are associated with susceptibility or disease characteristics of multiple sclerosis (MS). In 247 MS patients and 194 controls, single nucleotide polymorphisms (SNPs) at position +869 (Leu10Pro) and position +915 (Arg25Pro) in the signaling sequence of the TGFB1 gene were determined, and the distribution of alleles, genotypes, and haplotypes was related to clinical data. In addition, magnetic resonance imaging (MRI) data were studied in a subgroup of patients (n = 96).

Osteopontin levels and increased disease activity in relapsing-remitting multiple sclerosis patients.

Osteopontin (OPN) has been identified as the most prominent cytokine-encoding gene expressed within multiple sclerosis (MS) lesions. Recently, we demonstrated that OPN plasma levels were elevated in active relapsing-remitting (RR) MS patients. In this longitudinal study, a trend was observed for OPN serum levels in relation to clinical exacerbations.

Quantitative 1H-MRS of healthy human cortex, hippocampus, and thalamus: metabolite concentrations, quantification precision, and reproducibility.

Purpose: To evaluate metabolite concentrations in cortical gray matter, hippocampus, and thalamus of healthy adults, and to investigate precision and reproducibility of quantitative proton magnetic resonance spectroscopy (1H-MRS) in these gray matter regions.

Materials And Methods: Quantitative single-voxel short echo-time spectra were obtained from healthy human cortex, hippocampus, and thalamus. Subjects were examined twice.

[New diagnostic criteria for multiple sclerosis in clinical practice].

In two women, aged 29 and 49 years respectively, and a man aged 44 years, neurological signs pointed to multiple sclerosis (MS). In 2001, an international panel of experts revised the diagnostic criteria for multiple sclerosis (MS), which had been in use since 1983. As before, the fundamental diagnostic criterion remains dissemination in time and place of neurological abnormalities suggestive of demyelination.

Role of magnetic resonance imaging within diagnostic criteria for multiple sclerosis.

The diagnosis of multiple sclerosis (MS) has been improved in recent decades with the incorporation of paraclinical investigations in diagnostic workup. In the last 15 years, magnetic resonance imaging (MRI) has become an especially valuable tool for supporting MS diagnosis, and specific imaging criteria became fundamental to the guidelines for the diagnosis of MS published in 2001 by an international panel (IP). The new IP criteria include MRI evidence of dissemination in space and time, making it possible to diagnose MS after a single clinical episode.

Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS.

Objective: To investigate the cognitive skills of patients with relapsing remitting multiple sclerosis (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) relative to healthy control subjects and to assess whether there is heterogeneity in the type of cognitive disabilities demonstrated by patients with different MS phenotypes.

Methods: RRMS patients (n = 108), SPMS patients (n = 71), PPMS patients (n = 55), and healthy control subjects (n = 67) underwent neuropsychological assessment with the Brief Repeatable Battery of Neuropsychological Tests.

Results: Relative to controls, cognitive performance of RRMS patients was deficient when tasks required higher-order working memory (WM) processes (Word List Generation, 10/36 Spatial Recall Test, Symbol Digit Modalities Test).