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Locally produced oligoclonal IgG bands (OCB) are present in the cerebrospinal fluid (CSF) of 95% patients with multiple sclerosis (MS)[2,3]. The most sensitive method for the detection of OCB is isoelectric focusing (IEF) [1]. Occasional patients with clinically definite MS lack evidence for intrathecal IgG synthesis [2,9]. This study was designed to compare brain magnetic resonance imagining (MRI) findings between CSF OCB positive and negative MS patients. The study comprised 22 OB negative patients with clinically definite MS and 22 OCB positive controls matched for age, disease duration, activity and course of MS. In the both groups clinical assessment was performed by using Expanded Disability Status Scale (EDSS) score. T2 weighted MRI of the brain was performed on a Siemens Magnetom (1.0 T). Lesions were countred and sized for 15 anatomically defined locations:7 periventricular (PV) and 8 non-periventricular (NPV) regions. An arbitrary scoring system weighted for lesions size was used to estimate total and regional lesions loads: a)1 point was given for each lesion with a diameter 1-5 mm, b) 2 points for one lesion with a diameter 6-10 mm, c) 3 points for one over 10 mm, and confluent lesions scored one extra point [16]. Atrophy were scored as follows: 0-normal size, 1-mild atrophy, 2-moderate atrophy and 3-severe atrophy. Mean score of total brain MRI loads was lower in OCB negative than in OCB positive MS patients (44 vs. 50) but the difference was not statistically significant. Mean periventricular (32 vs. 23) non-periventricular (26 vs. 19) and infratentorial (11 vs. 9) scores were higher in OCB positive MS group in comparison with OCB negative patients but non-significant (figure 1). There was no correlation between EDSS score and total MRI lesions load in OCB negative MS patients, while in OCB positive group we detected significant correlation between EDSS score and total MRI lesions load (p=0.026) (figure 2). The results of this study demonstrate that by using conventional brain MRI the extent end severity of the pathological process seems to be similar in OCB negative and OCB postive MS patients. On the other hand, we found statistically significant correlation between brain MRI total lesion load and EDSS in the OCB positive MS patients, while this correlation was not detected in OCB negative MS patients. Differences in brain MRI findings between OCB positive nad OCB negative MS patients have been already analyzed [9,12]. In the first, Zeman et al. reported that OCB negative MS patients have lower total MRI brain lesion loads in comparison to OCB positive group, but the differences was not statistically significant [9]. In accordance with these findings Fukazawa et al. also failed to show differences in the distribution, extent shape and number of brain MRI lesions between OCB positive and negative MS patients. [12]. On the other hand, it has been demonstrated that the rate of intrathecal IgG synthesis apparently correlates with plaque volume in the brain, as demonstrated on MRI, in MS patients [17]. However, our results along with those from two above-mentioned previous studies do not support this notion. In conclusion, trend towards lesser MRI lesion load and lack of its correlation with EDSS in OCB negative MS patients, warrants further investigations with new MRI techniques (magnetic resonance spectroscopy and magnetisation transfer), including the thorough exploration of normal-appearing white matter, in OCB negative MS patients.

OBJECTIVES To estimate the distribution of multiple sclerosis in the Belgrade population. METHODS All persons who were affected and/or died from multiple sclerosis (Poser's criteria), with residence in the Belgrade region had been collected from January 1, 1985 to December 31, 1996. Prevalence was adjusted by direct method, using world population. RESULTS From 1985 to 1996, 823 patients were suffering from multiple sclerosis. Sex ratio was 1:1.9. The mean age at onset was 32.2 +/- 9.8 years. A relapsing-remitting course of multiple sclerosis was reported in 50.7% patients, secondary progressive in 36.4%, patients, and primary progressive in 12.9% patients. On December 31, 1996, age-adjusted prevalence of multiple sclerosis in Belgrade was 41.5/100,000, 28.2/100,000 for males, and 54.1/100,000 for females. During the period studied, statistically highly significant increasing trend of multiple sclerosis prevalence was observed (P = 0.0001). CONCLUSIONS According to findings presented in this study, Belgrade is an area with high prevalence of multiple sclerosis.

In a hospital-based study of 119 patients with definite multiple sclerosis, demographic and clinical factors were analysed with respect to their validity in assessing the long-term prognosis. Over a mean follow-up of 21.7 years, the following factors negatively influenced the prognosis by the univariate analysis: male sex, age at onset over 25, pyramidal involvement or spasticity at onset, 53 functional systems affected at onset or after 5 years, incomplete first remission, length of the first remission 41 year, 45 attacks in the first 10 years, secondary or primary-progressive disease, time to reach secondary progression over 5 years and time to reach EDSS 6 over 7 years. The multivariate model showed that in patients with relapsing-remitting disease, 5 years after onset, pyramidal involvement at onset and shorter time to reach EDSS 6 predicted poor outcome, while after 10 years, higher age at onset and incomplete first remission indicated poor prognosis. Ten years after onset, the predictors of poor outcome in the secondary-progressive group were shorter time to reach EDSS 6 or secondary progression and higher EDSS, while in the primary-progressive group those variables were spasticity or higher number of functional systems affected at onset, and higher EDSS after 5 and 10 years.

We describe two cases in which multiple sclerosis (MS) occurred in association with tomaculous neuropathy, presenting as chronic, distal sensorimotor polyneuropathy. In Case 1, monoclonal gammopathy of undetermined significance with monoclonal IgG λ reactive against GM1 ganglioside, was also detected. The diagnosis of tomaculous neuropathy was established after sural nerve biopsy. Teased fibers examination revealed focal `sausage-like' thickenings of the myelin sheaths in intact fibers and in fibers with segmental demyelination. Electron microscopy showed them to be due, mostly, to multiple windings of redundant myelin and concentric apposition of numerous lamellae, in contact with an intact myelin sheath. These are the first reported cases of tomaculous neuropathy in patients with MS. Whether the combination of the two conditions is purely coincidental or suggests the possible causal relation between MS and tomaculous neuropathy, is not certain.

Ten patients in acute exacerbation of multiple sclerosis were treated with 1000 mg of methylprednisolone for 7 days, followed by abrupt cessation of therapy. The function of hypothalamic-pituitary-adrenal (HPA) axis was assessed by the response of ACTH and cortisol to insulin tolerance test (ITT). ITT was performed 1 day before and 1, 3, 8, 13 and 23 days after the termination of the therapy (days 0, 8, 10, 15, 20 and 30 of the study, respectively). The response of these hormones to insulin-induced hypoglycemia prior to therapy was normal. There was no suppression of the ACTH response to hypoglycemia after the methylprednisolone therapy based on the 100% rise of ACTH after ITT. Cortisol response during ITT was suppressed at day 8 (1 day after ending of therapy) but recovered on day 10 (3 days after ending of therapy). In conclusion, 7 day-therapy with 1000 mg methylprednisolone does not result in the permanent suppression of the HPA axis, suggesting that no regular supplemental corticosteroid coverage is required. The observed transitory suppression of the HPA axis recovered spontaneously after the therapy.

The aim of our study was to analyse clinical and paraclinical characteristics of patients with multiple sclerosis (MS) with previous diagnosis of primary-progressive (PP) MS according to the Poser's criteria and further investigate if they fulfil the McDonald's diagnostic criteria for this disorder. A total of 561 MS patients were registered in the database at the Institute of Neurology, Belgrade, from 1 January 1997 to 31 December 2000 and 63 of them (11.2%) with previous diagnosis of PPMS were analysed retrospectively. Male/female ratio was 1.3:1 and mean age at onset 33.2 years. Most frequent at onset were pyramidal (in 73% of patients) and sensory symptoms (in 41% of patients); 74.6% of patients had greater than or equal to nine brain magnetic resonance imaging (MRI) lesions. Intrathecal oligoclonal immunoglobulin G (IgG) was detected in 96.7% and prolonged visual evoked potentials (VEP) P100 latency in 82.4% of patients. Of the total study group of 561 patients, 10.2% fulfilled the recently recommended McDonald's diagnostic criteria for the diagnosis of PPMS. Our findings further support the significance of the brain/spinal cord MRI, cerebrospinal fluid and VEP findings for precise diagnostic assessment in patients with suspected PP form of MS.

The levels of uric acid (UA), a natural peroxynitrite scavenger, were measured in sera from 240 patients with multiple sclerosis (MS) and 104 sex- and age-matched control patients with other neurological diseases (OND). The mean serum UA concentration was lower in the MS than in the OND group, but the difference did not reach the level of statistical significance (P = 0.068). However, the mean serum UA level from patients with active MS (202.6 + 67.1 mumol/l) was significantly lower than that in inactive MS patients (226.5 + 78.6 mumol/l; P = 0.046) and OND controls (P = 0.007). We found a significant inverse correlation of serum UA concentration with female gender (P = 0.0001), disease activity (P = 0.012) and duration (P = 0.017), and a trend towards an inverse correlation with disability as assessed by EDSS score, which did not reach statistical significance (P = 0.067). Finally, multivariate linear regression analyses showed that UA concentration was independently correlated with gender (P = 0.0001), disease activity (P = 0.014) and duration of the disease (P = 0.043) in MS patients. These findings suggest that serum UA might serve as a possible marker of disease activity in MS. They also provide support to the potential beneficial therapeutic effect of radical-scavenging substances in MS.

Oligoclonal immunoglobulin D bands were detected by isoelectric focusing in 7 out of 25 unconcentrated cerebrospinal fluid (CSF) samples obtained from patients with tumours of the central nervous system (CNS). The tumours were confirmed by clinical and histological findings. Two patients with CNS malignancy had intrathecal synthesis of oligoclonal bands both IgD and IgG. Four patients with a variety of CNS tumours had a systemic IgD immune response but no oligoclonal IgG bands. One patient with the most malignant tumour histology had a systemic IgD response as well as local synthesis of IgG. The study reveals several new aspects regarding CNS tumours: they are immunologically active and are capable of invoking oligoclonal immunoglobulin production both within the CNS and systemically. Multiple immunoglobulin activation can be found in malignant CNS tumours, and systemic IgD production may occur independently from IgG synthesis and may represent an immune response to a neoantigen produced in the CNS compartment.

The aim of this study was to assess the effects of high-dose (i.e. 1000 mg per day) intravenous methylprednisolone (HDMP) on event-related potentials (ERPs), elicited by a standard auditory 'oddball' paradigm, in patients with clinically active multiple sclerosis. In a double-blind study design, forty-four consecutive inpatients were randomly assigned in two clinically similar groups of 22 subjects each; one treated with HDMP for five days, and other with placebo. ERPs were recorded before and after the treatment. After HDMP therapy the P3 peak latency was significantly shortened (P=0.006), while peak latencies of other waves (i.e. N1, P2, and N2) remained unchanged. On the other hand, ERPs were uninfluenced by placebo treatment. Our results suggest the beneficial effect of intravenous HDMP therapy on, at least some aspects of, cognitive processing capabilities (as assessed by the auditory ERPs) in patients with multiple sclerosis.

We report a 51-year-old woman with vitamin B12 deficiency who presented with slight megaloblastic anemia and severe neurologic deficits associated with multiple focal and confluent T2-weighted white matter hyperintensities on brain MRI. Forty-four months after initiation of hydroxocobalamin therapy, there was clinical improvement and striking reduction in the MRI abnormalities. B12 deficiency should be considered in the differential diagnosis of neurologic disorders associated with multiple areas of white matter hyperintensities on T2-weighted brain MRI.

Concentrations of interleukin (IL)-12 and tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) were measured in patients with multiple sclerosis (MS) and control patients with non-inflammatory neurological diseases (NIND) by an enzyme-linked immunosorbent assay. TNF-alpha was detectable in the CSF of 60% of the patients with active MS, none of those with inactive MS and 29% of patients with NIND. CSF concentrations of TNF-alpha correlated with the degree of disability in MS patients (P0.05). Detectable levels of IL-12 were found in 10% of the MS CSF samples and 18% of NIND CSF samples. There was a significant relationship between CSF concentrations of IL-12 and those of TNF-alpha in MS patients (P0.05); no relationship was observed between the presence of IL-12 and disease activity or severity. These findings further stress the involvement of T helper 1 type-response within the central nervous system in MS.

Publisher Summary This chapter presents a study in which TGFβ1 in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) was assayed. Cerebrospinal fluid (CSF) samples from 32 patients (23 female and 9 male) with definite MS were studied; the mean age was 35 years (range 17–48 years) and the duration of the disease varied between three months and 19 years (mean four years). Disease severity was scored on Kurtzke's Expanded Disability Status Scale (EDSS), and the patients were classified as having either active or inactive MS. TGFβ1 was detected in 23 of 32 patients (72%) with MS, and in 2 of 11 (18%) control patients. Control patients with detectable TGFβ1 had diagnoses of cervical spondylotic myelopathy and brain tumor. CSF TGFβ1 concentrations in MS patients were significantly higher than in controls, whereas the concentrations failed to differentiate between patients with active MS and those with inactive disease. These findings document the in situ involvement of TGFβ1 in the pathogenesis of MS.

The antiphospholipid antibody syndrome is a disorder characterised by the production of autoantibodies directed against negatively charged cell membrane phosholipids. Antiphospholipid antibodies have been described in various neurological disorders. It has been generally accepted that viral, bacterial, and parasitic infections can serve as a trigger factor for autoimmune reactions. Despite the growing knowledge that has accumulated, the relation between parasites and autoimmunity has not been clarified. Enterobius vermicularis (pinworm) is a nematode rarely found outside the gastrointestinal tract, but allergic reaction due to enterobiasis has been reported.1 We describe the case of transverse myelopathy preceded by intestinal pinworm infestation in the primary antiphospholipid antibody syndrome. To our knowledge, such an association has not been reported previously. Pinworm therapy was complicated by the Jarisch-Herxheimer reaction manifested by temporary exacerbation of pre-existing neurological symptoms. In March 1998, a 40 year old woman who complained of perianal itching noticed the presence of worms migrating from the anus. Three days later itching and numbness involved both legs, and the patient had weakness in the legs. These symptoms progressed over the next 3 days to severe paraparesis and urinary urgence. Her medical history was relevant for three unexplained miscarriages …