H.-F. Petereit

New diagnostic criteria for multiple sclerosis

Background: Recently developed diagnostic criteria for MS (McDonald criteria) indicate that in patients with a single demyelinating episode (clinically isolated syndromes [CIS]), evidence for dissemination in space and time, essential for diagnosis, may be provided by MRI. Objective: To assess the usefulness of these new criteria in patients with CIS suggestive of MS. Methods: A total of 139 patients with CIS followed for a median of 3 years underwent brain MRI within 3 months of their first attack and again 12 months later. The number and location of lesions at baseline, the development of new lesions at follow-up, and the results of CSF examination (which, if positive, requires fewer MR abnormalities for diagnosis) were analyzed. The new McDonald criteria (incorporating MRI) were compared to the existing Poser diagnostic criteria and their accuracy was evaluated. Results: At 12 months, 11% had clinically definite MS according to the Poser criteria compared to 37% with the McDonald criteria. Eighty percent of patients fulfilling these new criteria developed a second clinical episode within a mean follow-up of 49 months. The new criteria showed a sensitivity of 74%, specificity of 86%, and accuracy of 80% in predicting conversion to clinically definite MS. Conclusion: One year after symptom onset, more than three times as many patients with CIS were diagnosed with MS using new diagnostic criteria incorporating MRI results compared to older criteria. However, the proposed MRI criteria require further prospective studies to optimize sensitivity and specificity. NEUROLOGY 2003;60:27–30 An International Panel on MS diagnosis has recently published new diagnostic criteria for MS (McDonald criteria).1 These diagnostic criteria focus on the objective demonstration of dissemination of lesions in time and space. Paraclinical diagnostic tools, mainly MRI, have been integrated into these criteria in order to facilitate the diagnosis of MS in patients with clinically isolated syndromes (CIS) suggestive of MS. In these patients with one attack and objective clinical evidence of one lesion, the demonstration of dissemination of lesions both in space and time is necessary to make a diagnosis of MS. The existing criteria by Poser et al. require the occurrence of a second clinical attack to fulfill the criteria for clinically definite MS (CDMS).2 In contrast, the new criteria allow the occurrence of lesions on MRI to fulfill the requirements for dissemination in space and in time. Different radiologic criteria have been developed in the past by which MRI abnormalities can be classified according to the strength with which they suggest a diagnosis of MS. The panel agreed that stringent criteria for MRI abnormalities should be followed in making a diagnosis of MS. Among available criteria, the panel selected the Barkhof dichotomized four-criteria MRI model to demonstrate dissemination in space.3,4 It was also decided that in patients who had abnormal CSF (detection of oligoclonal bands [OB] or raised IgG index), the presence of two or more lesions was sufficient to demonstrate dissemination in space.1 It was agreed that new T2 or gadolinium-enhancing lesions appearing at least 3 months after the onset of the clinical event would satisfy MRI criteria for dissemination in time.1 The impact of this major change on the way in Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of

Rituximab in a patient with multiple sclerosis – effect on B cells, plasma cells and intrathecal IgG synthesis

Objective –  To study the time course of immunoglobulin, B and plasma cells in the blood and cerebrospinal fluid (CSF) before and during rituximab treatment in a patient with severe relapsing–remitting multiple sclerosis (MS) in relation to clinical and MRI findings.

Difficulties in the differentiation of chronic inflammatory diseases of the central nervous system : value of cerebrospinal fluid analysis and immunological abnormalities in the diagnosis

Objectives –  A number of neurological syndromes may be evoked by involvement of the nervous system due to systemic diseases such as lupus erythematodes, sarcoidosis, Behçets disease and Sjögrens syndrome (SS) and may be confounded with another chronic inflammatory disease which is restricted to the central nervous system, e.g. multiple sclerosis (MS). Because of different treatment strategies, it is important to distinguish between these different autoimmune diseases.

Long‐term persisting interferon beta‐1b neutralizing antibodies after discontinuation of treatment

Objectives – Neutralizing antibodies (NAB) against interferon beta (IFNB) with presumably negative impact on treatment outcome have been described in up to 42% of patients undergoing IFNB treatment. However, in most cases NAB decrease despite continuation of IFNB therapy. Observations on NAB after discontinuation of IFNB therapy are lacking. Here, we report for the first time on NAB which now persist for several years following discontinuation of IFNB treatment.

The immunomodulatory properties of in vitro immunoglobulins are dose-dependent

Objectives – The mechanism by which intravenous immunoglobulins (immunoglobulin G, IgG) exert their beneficial effect on multiple sclerosis (MS) is unknown. Furthermore, there is uncertainty about the optimal dosage of IgG. Therefore, we investigated the influence of different IgG dosages on cytokine production in MS.

Stroke after initiation of interferon-beta treatment for relapsing-remitting disseminated white matter disease.

Background –  Interferon‐beta (INF‐β) is effective and used in reducing exacerbation frequency and disease progression in multiple sclerosis. In certain circumstances, INF‐β can lead to rare side effects.

Beta-trace protein as sensitive marker for liquorrhea.

Dear Sirs, We would like to comment on Reiber et al.: Beta-trace protein as sensitive marker for CSF rhinorhea and CSF otorhea . Acta Neurologica Scandinavica 2002; 106: 443–444. The beta-trace protein is indeed an ideal marker for liquorrhoea. It is astonishing that only few centres are using it, since the protein was described first in 1961 (1). We agree that this publication contains important original data, but we do not accept the conclusion. The authors stated that the sensitive detection of a CSF leakage is actually based on two methods: the immunoblot for b2-transferrin and the immunonephelometric assay of beta-trace protein as described by Felgenhauer et al. in 1987 (2). The beta-trace protein values in three (or four with ear secretions) different body fluids are described. Lumbar CSF samples (n 1⁄4 132), serum samples (n 1⁄4 132), nasal secretion samples (n 1⁄4 29) and CSF rhinorhea samples (n 1⁄4 20) were reported to be investigated using the N Latex b-Trace Protein research assay (Dade Behring, Germany). The authors described the mean value in serum at 0.59 mg/l, whereas lumber CSF had a mean value of 18.4, nasal secretion of 0.016 and fluid from CSF fistula of 2.4 mg/l. Using these data, the authors proposed a cut-off for beta-trace protein at 0.35 mg/l. The publication of Felgenhauer and co-workers does not contain information on the nephelometric assay of beta-trace protein. Felgenhauer used a one-dimensional semiquantitative immunelectrophoresis, called rocket electrophoresis. The first publications on the predictive values of beta-trace protein using the nephelometric assay were published in 2001 and 2002 (3, 4). In the published study, the diagnosis CSF rhinorhea was neither confirmed nor excluded by any other diagnostic method. It is not stated in the article, how the diagnosis CSF rhinorhea was defined at all. Hence, the study design does not allow recognizing false positive or false negative results. Of even more concern, the cut-off was proposed at a value below the mean serum value. The most important cause of CSF leakage is trauma, either by surgical or by other means (5). A trauma will always lead to contamination of blood or serum in the sample. When contaminated with blood or serum the beta-trace protein value will be increased in a sample containing nasal secretion whereas the beta-trace protein value will be decreased by contamination with blood or serum in a sample consisting of CSF. In our opinion, samples containing blood or serum are mandatory as control group when the calculation of the cut-off is on stage. To illustrate this point, we applied the proposed cut-off to our own materials investigated with the same nephelometric method, published in 2002 (4, 6). In the first study, we investigated the predictive values of beta-trace protein for the identification of CSF. Data from 84 patients were studied. In this material, there were 25 samples from 16 patients with values between 0.35 and 6.0 mg/l. Three of these 16 patients had a CSF fistula proven by other diagnostic means or surgical exploration. In the remaining 13 patients, a CSF fistula was not found, using high-resolution CT in 15 cases, CT cisternography in one case, MR in two cases, intrathecal sodium-fluorescein in one case, radionuclide cisternography in one case and surgical exploration in ten cases. In conclusion, the proposed cut-off would mean that 13 subjects (15.4%) would have had false positive results. In another study, we investigated the incidence of occult CSF fistula during paranasal sinus surgery. Sixty-seven of 69 patients (97.1%), operated on the paranasal sinuses, using endoscopic surgery, would have had an occult CSF fistula. In our opinion, false positive results in 15.4% and occult CSF fistulas in 97.1% of standard paranasal sinus surgery are not acceptable. Arrer and co-workers proposed a cut-off at 1.31 mg/l. Using this cut-off, they found two false positive samples (5). If a specificity of 100% is demanded an even higher cut-off value has to be applied (3). Acta Neurol Scand 2004: 110: 337–338 DOI: 10.1111/j.1600-0404.2004.00318.x Printed in UK. All rights reserved Copyright Blackwell Munksgaard 2004

Detecting infectious agents in central nervous system inflammation by cerebrospinal fluid analysis

Cerebrospinal fluid analysis is the method of choice in CNS infection and provides the basis for appropriate treatment. Due to the proximity of CSF and CNS, the infectious agent may be detected directly by microscopy or antigen or nucleic acid detection--the latter by polymerase chain reaction--in native CSF or after culture. Furthermore, intrathecal antibody synthesis against the infectious agent may identify the cause of infection. This indirect antigen detection method requires correction for a systemic antibody response and a blood-CSF barrier disturbance. The following text gives an overview of appropriate detection methods and their relevance to the most important CNS infections.

Liquoranalytik in der Diagnostik erregerbedingter Erkrankungen des Zentralnervensystems

Cerebrospinal fluid analysis is the method of choice in CNS infection and provides the basis for appropriate treatment. Due to the proximity of CSF and CNS, the infectious agent may be detected directly by microscopy or antigen or nucleic acid detection--the latter by polymerase chain reaction--in native CSF or after culture. Furthermore, intrathecal antibody synthesis against the infectious agent may identify the cause of infection. This indirect antigen detection method requires correction for a systemic antibody response and a blood-CSF barrier disturbance. The following text gives an overview of appropriate detection methods and their relevance to the most important CNS infections.

Liquoranalytik in der Diagnostik erregerbedingter Erkrankungen des Zentralnervensystems@@@Detecting infectious agents in central nervous system inflammation by cerebrospinal fluid analysis

Cerebrospinal fluid analysis is the method of choice in CNS infection and provides the basis for appropriate treatment. Due to the proximity of CSF and CNS, the infectious agent may be detected directly by microscopy or antigen or nucleic acid detection--the latter by polymerase chain reaction--in native CSF or after culture. Furthermore, intrathecal antibody synthesis against the infectious agent may identify the cause of infection. This indirect antigen detection method requires correction for a systemic antibody response and a blood-CSF barrier disturbance. The following text gives an overview of appropriate detection methods and their relevance to the most important CNS infections.