BACKGROUND Intrathecal IgG synthesis (ITGS), in conjunction with magnetic resonance imaging, can help in the early diagnosis of multiple sclerosis (MS). Recently, we developed a new oligoclonal IgG ...band (OCGB) test for ITGS detection that is more sensitive and easier to interpret than previously described methods. OBJECTIVE To assess the accuracy of a new OCGB detection test in the diagnosis of MS. DESIGN Prospective observational study. SETTING A hospital neurology department. PATIENTS A total of 385 patients with various neurologic disorders. MAIN OUTCOME MEASURES The sensitivity and specificity of the OCGB detection test for MS diagnosis. RESULTS Intrathecal IgG synthesis was found in 127 patients with MS (96.2%), 18 (35.3%) with central nervous system infections, and 1 with motor neuron disease. Two patterns reflected ITGS. One pattern, showing OCGBs restricted to cerebrospinal fluid, was predominantly found in MS. The other pattern, with OCGBs in serum and additional bands in cerebrospinal fluid, was mostly found in central nervous system infections. No patients with other inflammatory neurologic diseases showed ITGS. These patients frequently displayed a mirror pattern, with identical bands in serum and cerebrospinal fluid. Considering all patients, the sensitivity for the diagnosis of MS was 96.2%, and the specificity was 92.5%. Excluding infections, which usually do not present a differential diagnosis problem with MS, the sensitivity was still 96.2%, and the specificity increased to 99.5%. CONCLUSION The accuracy of this OCGB method reinforces the value of cerebrospinal fluid studies in the early differential diagnosis of MS.Arch Neurol. 2005;62:574-577-->
Objective– A protocol system is being used in Spain for the prescription of innovative drugs including interferon beta‐1b (IFNβ‐1b). Petitions for dispensing and reimbursement are based on the ...inclusion and exclusion criteria of pivotal trials, and are reviewed individually for approval by specialist committees. To estimate the performance of IFNβ‐1b in the clinical setting, data collected by the INSALUD and regional health services of Andalusia and Catalonia, together responsible for the healthcare of nearly 30 million individuals, were compiled in a common database for analysis. Methods– Data comprise demographic and disease characteristics at the time of petition and at follow‐up 3 months after treatment initiation and every 6 months thereafter. Efficacy was estimated by mean number of relapses per year, proportion of relapse‐free patients, and disease progression as measured by the Expanded Disability Status Scale (EDSS). Safety parameters included adverse events and laboratory analyses. Results– Between September 1995 and database cutoff in mid‐1998, petitions of 1419 patients were approved for IFNβ‐1b treatment. Patients were homogenous across the three databases and in the subgroups of patients completing 1 year (n=940) and 2 years (n=302) of treatment. There was a marked decrease in the mean number of relapses in the first 12 months of IFNβ‐1b treatment for the 938 patients documented for 12 months, with a mean of 0.4 (±0.7 SD) relapses per patient and year, and a 2‐year mean of 0.9 (±1.20 SD) in the 302 patients documented for 24 months. Of the 938 patients followed for ≥12 months, 505 (53.8%) were documented as being relapse‐free during 12 months of treatment, and 146 (48.3%) of the 302 patients followed for ≥24 months, were relapse‐free during 24 months of treatment. There were no differences in mean or median EDSS scores between baseline and months 12 and 24. Skin disorders were the most frequent adverse events, reported in over one‐third of all patients; there were 159 injection site events, most frequently erythema (115 events). Systemic AEs pointing towards flu‐like symptoms were reported in 288 of 1419 patients (20.3%). Leukopenia was the most frequently reported laboratory event. Elevations in liver transaminases were noted for 12 patients (0.8%) with SGOT increase and 7 (0.5%) with SGPT increase. Conclusion– The protocol system has helped make IFNβ treatment available to 8–10% of the estimated 15,000–18,000 MS patients in the regions studied. In terms of efficacy, IFNβ‐1b performed in line with the pivotal study results. The safety profile of IFNβ‐1b was consistent with the published findings and the drug labelling, and no new side effects or increased incidence of known side effects was observed.
We studied the effect of intravenous methylprednisolone (MP) on the expression of the integrins, LFA-1 and VLA-4, on activated blood T-lymphocytes in 17 patients with relapses of clinically definite ...relapsing-remitting MS. MP treatment did not induce changes in the expression of CD3, CD4, DR, LFA-1 or VLA-4 markers when measured in the total population of lymphocytes in MS patients in relation to treatment. Treatment influenced neither the LFA-1 nor VLA-4 positive cells within the CD3+ population. MP treatment clearly decreased the DR+ CD3+ cells (P < 0.01) and the percentage of DR+ CD3+ lymphocytes bearing VLA-4 (P < 0.01). However, this was not the case when we studied the percentage of lymphocytes which expressed LFA-1. Glucocorticoids did not influence the mean intensity of the expression of the two integrins quantified in either total or DR+ CD3+ lymphocytes. Although, further research seems warranted to investigate a possible effect of MP on lymphocyte integrin function, this work corroborates the idea that MP treatment may interfere with the mechanisms of T-cell migration into CNS, thus modulating the activity of multiple sclerosis.
Five patients showed the pupil abnormality contralateral to the epileptic scalp EEG focus and three had ipsilateral mydriasis. 2 The exact pathophysiology of pupil changes during seizures remains ...unclear; it has been stated that miosis would represent an excitatory component 3 whereas dilatation would be interpreted as a negative ictal phenomenon. 1 Descending inhibition of the Edinger-Westphal nucleus would result in pupillary dilatation and impairment of the pupillary light reflex; this could be mediated by leu-enkephalin fibres which may produce pronounced inhibition of this nucleus in experimental studies. 4 Animal experiments performed in macaques showed that electrical stimulation of the anterior occipital lobe produced contralateral ocular deviation with asymmetric dilatation of both pupils that was greater in the homolateral eye 5 ; these features were found in our patient, although we did not see changes in the diameter of the left pupil and the reason for this disparity is unknown.
In vitro studies have shown that the cerebrospinal fluid of patients with multiple sclerosis transports compounds which may affect the function or viability of central nervous system cell function. ...The presence of nerve ion channel blockers and other molecules, as yet unidentified, which may cause the death of nerve cells or oligodendrocytes has been shown, although their relevance and clinical correlation is still not clear. If their usefulness is proved, these methods may be useful in the search for inhibitors of the noxious effects of the substances mentioned.
The proliferative response (PR) of peripheral blood mononuclear cells (PBMC) to lectins such as phytohemaglutinin (PHA), anti-CD3 monoclonal antibodies such as OKT-3 or phorbol esters such as ...tetradecanoyl-phorbol 13-acetate (TPA) was investigated in 18 stable multiple sclerosis (MS) patients (9 untreated and 9 treated patients) and 10 healthy controls. PBMC from untreated MS patients showed a significantly higher PR to PHA than healthy controls. The PR of PHA, anti-CD3 or TPA stimulated PBMC from treated patients was lower than that from untreated MS patients. Mitogen stimulated PBMC from untreated patients shown both increased sensitivity to the stimulatory effect of IL-2 and increased resistance to the inhibitory effect of IL-10 and IFN-alpha. The addition of IL-2 increased the PR in PHA-stimulated PBMC from untreated MS patients, but not in those from treated MS patients and healthy controls. Mitogen stimulated cells from untreated patients were more resistant to the inhibitory effect of IL-10 and IFN-alpha than PBMC from either treated MS patients or healthy controls. Cyclosporine A (CsA) inhibited the PR and the expression of activation antigens induced by PHA in PBMC from the three groups of subjects. This inhibitory effect of CsA have was enhanced by the addition of IFN-alpha.
The lateral bulbar syndrome is a heterogeneous clinical condition. It is usually of vascular origin, due to a reduction in postero inferior cerebellar artery (PICA) and vertebral artery blood flow.
...We studied two cases: a woman aged 59 years and a man of 49 years, who were admitted with Wallenberg s syndrome. The diagnosis was confirmed on magnetic resonance which showed an ischaemic lesion in the lateral bulbar region ipsilateral to the clinical signs. On angioresonance there was lack of filling of the vertebral artery involved, and the PICA was not seen.
At the present time, the most sensitive technique available for the diagnosis of the lateral bulbar syndrome is cranial magnetic resonance (it even appears to be useful for making aetiopathogenic hypotheses). Similarly, arteriography is widely used for assessing disorders of the posterior cerebral circulation, although it is not without risk. According to recent studies, angioresonance gives sensitivity and specificity of over 75% when used to assess anomalies of the vertebral and basilar arteries. So our observations corroborate the finding that angioresonance is a very sensitive, specific investigation for showing disorders of the vertebral arteries and PICA, which spares patients the morbidity associated with conventional arteriography.
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