Measles antibodies, κ-λ light chain distribution and immunoglobulins in serum,cerebrospinal fluid and brain of a patient affected with multiple sclerosis

Summary The serum, cerebrospinal (CSF) and brain of a patient (NAG) affected with multiple sclerosis (MS) were examined for measles antibodies with CF and HI techniques, and the - light chain ratios of all samples available were evaluated. - populations of the matched serum, CSF and brain specimens were all -predominant and in agreement with each other; the light chain distribution of the brain specimens confirmed previous findings [3].Only the serum immunoglobulins showed significant measles antibody titers, but slightly increased measles antibody titers were also observed in ventricular plaques.The amount of immunoglobulin G (IgG) synthesized per day by the central nervous system (CNS) was estimated.The IgG synthesis in CNS NAG (11.6mg/day) was above the upper limit of the normal range (3.3 mg/day), but apparently there was no positive correlation between the intracerebral IgG synthesis and specific anti-measles IgG.

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Zusammenfassung Das Serum und der Liquor sowie das Gehirn eines Patienten (NAG), der an Multipler Sklerose (MS) litt, wurden auf das Vorhandensein von Masernantikörper mit der CF- und HI-Technik untersucht und die --Relation der leichten Ketten aller vorhandenen Proben wurde ausgewertet. In allen Proben lag eine -Dominanz vor, sowohl im Serum, im Liquor als auch im Gehirn. Die Verteilung der leichten Ketten in den Gehirnproben bestätigt frühere Ergebnisse [3].Nur in den Serumimmunoglobulinen konnten signifikante Masernantikörpertiter nachgewiesen werden, jedoch waren leicht erhöhte Masernantikörpertiter auch in den ventrikelnahen Plaques vorhanden.Es wurde die Menge des täglich durch das zentrale Nervensystem synthetisierte Immunoglobulin G (IgG) geschätzt.Die IgG-Synthese im Zentralnervensystem der Patientin NAG (11.6 mg/Tag) lag über der üblichen Normgrenze (3.3 mg/Tag) aber es schien keine positive Korrelation zwischen der intrazerebralen IgG-Synthese einerseits und den spezifischen Antimasern-IgG andererseits vorzuliegen.

     

Determinants of interferon β efficacy in patients with multiple sclerosis

Many patients with multiple sclerosis (MS) experience clinical relapses or progression of disability, or exhibit evidence of disease activity on MRI, despite the use of disease-modifying therapy. Although evidence clearly supports the efficacy of interferon β (IFN-β) in treating MS, the factors that determine the response to this drug in individual patients have not been fully elucidated. As more treatment options become available, the early identification of factors that can affect or predict the efficacy of agents in individual patients is important, because such knowledge facilitates early switching of treatment. Despite years of research and numerous reports of promising therapy markers for MS, few markers have emerged as clinically useful. Several studies suggest, however, that development of MRI lesions within 6-24 months after the initiation of IFN-β treatment predicts an unfavorable response. In addition, persistently high titers of neutralizing antibodies diminish or abrogate the therapeutic effects of IFN-β, and help to identify patients who do not respond. This Review highlights advances in research on the response to IFN-β in patients with MS and aims to provide a practical approach for incorporating clinical data, biological markers and MRI measures of disease activity into their therapeutic management.     

Study of binding and neutralising antibodies to interferon-β in two groups of relapsing-remitting multiple sclerosis patients

Interferon (IFN)-β is generally considered an effective treatment for multiple sclerosis (MS); however, some patients do not respond to this therapy, possibly due to the production of neutralising antibodies (NAB) which can prevent the biological effect of IFN-β. We compared the two types of IFN-β, the glycosylated IFN-β_1a and the non-glycosylated IFN-β_1b, as their chemical differences may entail differing immunogenic capacities. We studied 22 relapsing-remitting MS patients treated with IFN-β_1a and 31 treated with IFN-β_1b for 1 year, using the same assay and criteria, to compare the two types of IFN-β in their ability to induce binding and neutralising antibodies and examined the correlation of the findings with the clinical data. Binding antibodies to IFN-β_1a and IFN-β_1b were determined by enzyme-linked immunosorbent assay. A bioassay was used to detect and quantify the NABs to IFN-β, measuring the capacity of NABs to block the antiviral resistance induced by IFNs. Binding antibodies were found in 32 % of those treated with IFN-β_1a and in 52 % of those treated with IFN-β_1b; NABs were found in 14 % and 24 %, respectively. Both groups showed a significant decrease in relapse rate during the first year of treatment. These results demonstrate that the IFN-β_1b molecule is more immunogenic than the IFN-β_1a molecule. This may be due to the non-glycosylated, chemical structure of the former, which can produce aggregates and enhance antibody production. No association was found between the presence of NABs and the clinical status of the patients. Received: 8 February 2000 / Received in revised form: 1 August 2000 / Accepted: 22 November 2000     

The use of ID migraine™ questionnaire in patients with multiple sclerosis

Primary headaches are underdiagnosed and undertreated in patients with multiple sclerosis (MS). The aim of our study was to investigate the possibility of using the ID migraine™ (ID-M) questionnaire to make a first-line diagnosis of migraine in subjects affected by MS. We consecutively recruited 144 patients regularly attending the MS Centre of S. Andrea Hospital in Rome. Results from ID-M were matched with diagnoses of a blind neurologist. According to the ICHD-II criteria, 77 (53.5%) patients were diagnosed as suffering from migraine. ID-M showed high sensitivity (91%) and specificity (94%) in identifying patients with migraine. ID-M was also able to discriminate patients affected by headache following interferon beta therapy, having only the 10% out of these patients a positive ID-M. The use of the ID-M as a screening test is warranted not only in the epidemiological research, but also to ensure a better clinical management of patients with MS.     

Amyloid in a multiple sclerosis lesion is clearly of Aλ type

In rare multiple sclerosis cases amyloid is deposited in demyelinated plaques. In one such case amyloid was examined immunohistochemically with a panel of antibodies directed against different amyloid types. The amyloid was classified as the Aλ type produced by a local monoclonal B cell population. Received: 28 September 1999 / Revised: 17 March 2000 / Accepted: 20 March 2000     

Intracortical excitability in patients with relapsing–remitting and secondary progressive multiple sclerosis

We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing–remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients’ TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.     

MRI quantification of gray and white matter damage in patients with early–onset multiple sclerosis

Background and objective Contrary to what happens in adult–onset multiple sclerosis (MS), in a previous preliminary magnetic resonance imaging (MRI) study we showed only subtle normal–appearing brain tissue changes in patients with earlyonset MS. Our objective was to evaluate the presence and extent of tissue damage in the brain normalappearing white matter (NAWM) and gray matter (GM) from a larger population of patients with earlyonset MS. Methods Using diffusion tensor (DT) and magnetization transfer (MT) MRI, we obtained DT and MT ratio (MTR) maps of the NAWM and GM from 23 patients with early–onset MS and 16 sex– and age–matched healthy volunteers. Results Compared with healthy volunteers, patients with early–onset MS had significantly increased average MD (p = 0.02) and FA peak height (p = 0.007) and decreased average FA (p <0.0001) of the NAWM.Brain dual–echo lesion load was significantly correlated with average FA (r = –0.48, p = 0.02) and with FA peak height (r = 0.45, p = 0.03) of the NAWM. No MTR and diffusion changes were detected in the GM. Conclusions This study confirms the paucity of the ‘occult’ brain tissue damage in patients with earlyonset MS. It also suggests that in these patients GM is spared by the disease process and that NAWM changes are likely to be secondary to Wallerian degeneration of fibers passing through macroscopic lesions.     

Frequency and severity of headache is worsened by Interferon-β therapy in patients with multiple sclerosis

Patti F, Nicoletti A, Pappalardo A, Castiglione A, Lo Fermo S, Messina S, D’Amico E, Cimino V, Zappia M. Frequency and severity of headache is worsened by Interferon‐β therapy in patients with multiple sclerosis.
Acta Neurol Scand: 2012: 125: 91–95.
© 2011 John Wiley & Sons A/S. Background – The relationship between multiple sclerosis (MS) and headache (HA) is not well known. It was reported that interferon‐beta (IFNβ) could induce or worsen HA. Objective – To evaluate the impact of IFNβ treatment on HA and the relationship between HA and the various commercial preparations of IFNβ in mildly disabled patients with MS. Methods – A specific questionnaire was administered to 357 relapsing‐remitting MS patients. Characteristics of HAs were considered, including the temporal relationships with IFNβ administration. Results – One hundred and seventeen patients were treated with weekly intramuscular injections of interferon IFNβ‐1a (Avonex^®), 84 with subcutaneous injections of IFNβ‐1b (Betaferon^®) every other day, 48 and 108 with three times weekly subcutaneous injections of IFNβ‐1a (Rebif^®) 22 mcg or IFNβ‐1a (Rebif^®) 44 mcg, respectively. Three hundred and fourteen patients were affected by HA, and among them, 219 patients suffered of pre‐existing HA. In this latter group, 121 subjects (55%) noted a worsening of their HA after starting IFNβ therapy; this was more frequently reported by patients treated with Avonex^® and Rebif^® 44. Ninety‐five patients experienced new HA. Conclusion – IFNβ treatment could worsen HA in patients with pre‐existing HA or cause the appearance of new HA. Among different IFNβ preparations, Rebif^® 44 and Avonex^® seemed to be more cephalalgic than the other drugs.     

Health-related quality of life in patients with relapsing-remitting multiple sclerosis treated with subcutaneous interferon β-1a in Iran

Purpose: Multiple sclerosis (MS) requires long-term therapy and can affect many aspects of a patient's life, including quality of life. MS patients score lower on health-related quality of life (HRQoL) measures. The efficacy of subcutaneous interferon (IFN) β-1a has been extensively evaluated by using objective measures but its impact on HRQoL is currently unclear. In this observational study, we evaluated HRQoL of Iranian patients with relapsing-remitting MS (RRMS) treated with IFN β-1a by using short-form 36 (SF-36) and multiple sclerosis international quality of life (MusiQoL) questionnaires. Methods: Four hundred recruited RRMS patients were treated with human serum album free IFN β-1a for 1 year. Patients were required to fill in SF-36 and MusiQoL questionnaires at the first visit and at each follow-up visit. Expanded disability status scale (EDSS) evaluation was performed at baseline and at each visit. Comparisons in HRQoL between visits were calculated using Cohen's d effect size. The relationship between change in EDSS score and the score of each questionnaire was calculated using Pearson correlation coefficients. Results: Three-hundred and eighty three completed the study. Two-hundred and thirty nine were female. Mean (SD) age was 28.75 (±5.49). After 1 year, overall MusiQoL Index score effect size was ?0.16 and SF-36 physical component and mental component showed overall effect sizes of ?0.28 and ?0.53, respectively. Mean (range) EDSS change was 1 (1–4). Three-hundred and seventy four were clinically stable with mean (range) EDSS change of 0.1 (?2–0.5). Increase in EDSS was linked to a decrease in both MusiQoL and SF-36. Conclusion: We found that, HRQoL did not change significantly over the first year of therapy. Furthermore, decreases in HRQoL were inversely correlated with increases in EDSS score.     

Is cervical decompression beneficial in patients with coexistent cervical stenosis and multiple sclerosis?

Cervical stenosis (CS) and multiple sclerosis (MS) are two common conditions with distinctive pathophysiology but overlapping clinical manifestations. The uncertainty involved in attributing worsening symptoms to CS in patients with MS due to extremely high prevalence of asymptomatic radiological CS makes treatment decisions challenging. A retrospective review was performed analyzing the medical records of all patients with confirmed diagnosis of MS who had coexistent CS and underwent surgery for cervical radiculopathy/myeloradiculopathy. Eighteen patients with coexistent CS and MS who had undergone cervical spine decompression and fusion were identified. There were six men and 12 women with an average age of 52.7 years (range 40–72 years). Pre-operative symptoms included progressive myelopathy (14 patients), neck pain (seven patients), radiculopathy (five patients), and bladder dysfunction (seven patients). Thirteen of the 14 patients (92.9%) with myelopathy showed either improvement (4/14, 28.6%) or stabilization (9/14, 64.3%) in their symptoms with neck pain and radiculopathy improving in 100% and 80% of patients, respectively. None of the seven patients with urinary dysfunction had improvement in urinary symptoms after surgery. To conclude, cervical spine decompression and fusion can improve or stabilize myelopathy, and significantly relieve neck pain and radiculopathy in the majority of patients with coexistent CS and MS. Urinary dysfunctions appear unlikely to improve after surgery. The low rate of surgical complications in our cohort demonstrates that cervical spine surgery can be safely performed in carefully selected patients with concomitant CS and MS with a good clinical outcome and also eliminate CS as a confounding factor in the long-term management of MS patients.