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S Vukusic

Publications and source records attributed to S Vukusic.

16 recordsLinked to original sources

Myasthenia gravis exacerbation or unmasking associated with telithromycin treatment.

Telithromycin, a new ketolide antibiotic, has been implicated in the exacerbation or unmasking of myasthenia gravis. This retrospective study presents two clinical reports and summarizes eight other suspected cases notified to the French pharmacovigilance system, highlighting a potentially life-threatening risk of telithromycin treatment in myasthenic patients. An important common feature was that, in seven cases, symptomatology occurred within 2 hours of first telithromycin intake--notably in cases of severe exacerbation.

Adult↗

Unusual ocular motor findings in multiple sclerosis.

In multiple sclerosis (MS), nystagmus or internuclear ophthalmoplegia (INO) are the usual ocular motor dysfunctions. However, in patients with focal brainstem lesions, other rare manifestations may be observed, such as an isolated ocular motor nerve palsy or complex ocular motor disturbances. We report five MS patients with unusual ocular motor disturbances (bilateral third nerve palsy [n = 2], opsoclonus, Horner's syndrome and one-and-a-half syndrome). We discuss possible correlations between clinical disturbances and MRI abnormalities. Patients were seen in two MS centres. They had a confirmed diagnosis of MS and underwent a brain MRI and a complete neuro-ophthalmological work-up. In one case (opsoclonus), ocular motor manifestations were the first manifestation of MS. In the other four cases they occurred 3 months (Horner syndrome), 6 years and 12 years (bilateral third nerve palsy) and 2 years (one-and-a-half syndrome) after the disease onset, respectively. Four out of five patients were still in a relapsing-remitting form of MS. In the opsoclonus case, there was no evidence of a brainstem lesion. A gadolinium-enhanced lesion (2 cases) or a new T2-weighted lesion located in the brainstem correlated with the clinical presentation. All patients completely or partially recovered after corticosteroid infusions. Our study shows some rare or previously undescribed complex ocular motor symptoms in MS.

Adjuvants, Immunologic↗

[Multiple sclerosis and pregnancy].

The influence of pregnancy in multiple sclerosis (MS) has been a matter of controversy for a long time. Women with MS were often discouraged to envisage pregnancy. The Pregnancy in Multiple Sclerosis (PRIMS) study was the first large-scale prospective study aimed at assessing the possible influence of pregnancy and delivery on the clinical course of MS. Two hundred and fifty-four women with a diagnosis of MS were included during pregnancy and followed-up till the end of the second year post partum. The results were a reduction in the relapse rate during pregnancy, in comparison to the year before pregnancy, especially marked in the third trimester, and a significant increase in the relapse rate in the first trimester post partum. From the second trimester post partum on however, the relapse rate did not significantly differ from the pre-pregnancy rate. About one third of the women experienced a post partum relapse. Pregnancy did not influence disability progression. The clinical factors likely to predict a relapse in the three months after delivery were analyzed by logistic regression analysis. Women with a greater disease activity in the year before pregnancy and during pregnancy had a higher risk of relapse in the post partum three months. Neither breast-feeding, nor epidural analgesia correlated with presence of a post partum relapse. When comparing the predicted and observed status however, only 72 percent of the women were correctly classified by the multivariate model. It seems unwise therefore to use this kind of model to select women that would benefit from a putative preventive therapy. The PRIMS study had other major consequences: it fostered the development of specific therapeutic strategies to prevent post partum relapses (IV immunoglobulins, IV methylprednisolone), and suggested a potential role of sexual hormones in the natural history of MS during pregnancy and the post partum, therefore identifying them as a preferential target for prevention. The preventive effect of progesterone combined with estradiol on post partum relapses will be tested in a large-scale randomized and placebo-controlled European trial, the POPART'MUS study.

Adult↗

Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.

BACKGROUND: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. METHODS: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. RESULTS: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. CONCLUSION: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Adult↗

Clinical characteristics of responders to interferon therapy for relapsing MS.

OBJECTIVE: To determine the proportion of patients with multiple sclerosis (MS) who respond to interferon-beta (IFNB) therapy and assess whether clinical characteristics differ in IFNB responders vs nonresponders. METHODS: Data on all patients who received IFNB who were entered in the prospective European Database for Multiple Sclerosis (EDMUS) database in Lyon as of March 31, 2001, were reviewed. Responders were defined as having a lower relapse rate on IFNB compared with the year or 2 years prior to IFNB therapy. RESULTS: Two hundred sixty-two patients with relapsing MS received at least 6 months of IFNB: 200 relapsing remitting (RR) and 62 relapsing secondary progressive (SP). One-third of patients experienced a higher or identical annual relapse rate while on IFNB treatment. Compared with nonresponders, responders were older and had longer disease duration at the time IFNB was initiated. RRMS responders also had a higher relapse rate during the year prior to IFNB therapy and SPMS responders had a higher Disability Status Scale score at initiation of IFNB. CONCLUSION: Clinical profiles of patients with relapsing MS who respond to IFNB may differ from those who do not with a more inflammatory and less neurodegenerative disease at the time IFNB is initiated.

Adult↗

Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group.

BACKGROUND: There has been some concern that vaccination may precipitate the onset of multiple sclerosis or lead to relapses. Since the recent hepatitis B vaccination program in France, there have been new reports of an increased risk of active multiple sclerosis after vaccination. METHODS: We conducted a case-crossover study to assess whether vaccinations increase the risk of relapse in multiple sclerosis. The subjects were patients included in the European Database for Multiple Sclerosis who had a relapse between 1993 and 1997. The index relapse was the first relapse confirmed by a visit to a neurologist and preceded by a relapse-free period of at least 12 months. Information on vaccinations was obtained in a standardized telephone interview and confirmed by means of medical records. Exposure to vaccination in the two-month risk period immediately preceding the relapse was compared with that in the four previous two-month control periods for the calculation of relative risks, which were estimated with the use of conditional logistic regression. RESULTS: Of 643 patients with relapses of multiple sclerosis, 15 percent reported having been vaccinated during the preceding 12 months. The reports of 94 percent of these vaccinations were confirmed. Of all the patients, 2.3 percent had been vaccinated during the preceding two-month risk period as compared with 2.8 to 4.0 percent who were vaccinated during one or more of the four control periods. The relative risk of relapse associated with exposure to any vaccination during the previous two months was 0.71 (95 percent confidence interval, 0.40 to 1.26). There was no increase in the specific risk of relapse associated with tetanus, hepatitis B, or influenza vaccination (range of relative risks, 0.22 to 1.08). Analyses based on risk periods of one and three months yielded similar results. CONCLUSIONS: Vaccination does not appear to increase the short-term risk of relapse in multiple sclerosis.

Adult↗

[Multiple sclerosis: spontaneous course, natural history].

Globally, the course and prognosis of multiple sclerosis are heterogeneous, and generally considered to be unpredictable. Advances in statistical techniques have made it possible to analyze representative cohorts of patients to clearly delineate the overall prognosis of the disease, beyond individual variations. For each individual however, there appears to be a steady progression as shown by serial quantified neurological examinations. At the present time early prediction of outcome remains impossible. In the near future, new imaging techniques may provide a solution to this problem allowing selection of patients at risk who could benefit from early treatment.

Diagnostic Imaging↗

[Diagnostic criteria of different clinical forms ].

Multiple sclerosis (MS) is a disease of unknown origin and for which there is no specific diagnostic test. The diagnosis of MS is always the result of a more or less simple procedure, depending on the cases, and it remains uncertain until evidence of anatomo-pathological signs have been brought forward. An almost unanimous consensus does exist regarding several points. In the presence of suggestive or, at least, compatible neurological signs and in the absence of any alternative diagnosis according to a neurologist expert in MS, the diagnosis of MS is based on three criteria: the evidence of at least two different lesions in the white matter of the central nervous system, which is called the "space dissemination" criterion; the evidence of at least two different episodes in the disease course, which is called "time dissemination"; the evidence of a chronic inflammation of the central nervous system revealed through the analysis of the cerebrospinal fluid, i.e. the "infammatory" criterion. The observation of one or several of these criteria allows to establish the diagnosis of MS with more or less certainly, likely to be reassessed according to the subsequent course of the disease. There is a wide consensus today with Poser's classification (Poser et al., 1983) which combines the three criteria and distinguishes five different categories. According to Poser et al., space dissemination may be proved on clinical examination, but also with the brain MRI and, failing that, with the evoked potentials. Time dissemination is based only on clinical signs and the inflammatory criterion is as significant as the two other criteria. This classification has just been revised by an expert committee (McDonald et al., 2001) who wish to simplify it into two different categories (MS vs possible MS). It has been suggested that time dissemination should be proven by the observation of MRI signs three months at least after the previous clinical episode or the previous MRI. It has been suggested also to use the inflammatory criterion in second position in replacement of the space criterion when the latter is missing on the clinical and paraclinical levels. Time will say whether this new classification will replace the previous one.

Brain↗

Relapses and progression of disability in multiple sclerosis.

BACKGROUND: The influence of the patterns of onset of multiple sclerosis and relapses of the disease on the time course of irreversible disability is controversial. METHODS: In 1844 patients with multiple sclerosis who were followed for a mean (+/- SD) of 11 +/- 10 years, we determined the time of the clinical onset of the disease, the initial course (relapsing-remitting or progressive) and the subsequent course (relapsing-remitting, secondary progressive, or primary progressive), the times of relapses, the time to the onset of irreversible disability, and the time course of progressive, irreversible disability. We used three scores on the Kurtzke Disability Status Scale (range, 0 to 10, with higher scores indicating more severe disability) as measures of the severity and progression of disability: a score of 4 (limited walking ability but able to walk for more than 500 m without aid or rest), a score of 6 (ability to walk with unilateral support no more than 100 m without rest), and a score of 7 (ability to walk no more than 10 m without rest while leaning against a wall or holding onto furniture for support). We used Kaplan-Meier analyses to determine the influence of relapses on the time to the onset of irreversible disability. RESULTS: The median times from the onset of multiple sclerosis to the assignment of a score of 4, a score of 6, and a score of 7 on the disability scale were longer among the 1562 patients with a relapsing-remitting onset of disease (11.4, 23.1, and 33.1 years, respectively) than among the 282 patients who had progressive disease from the onset (0.0, 7.1, and 13.4 years, respectively; P<0.001 for all comparisons). In contrast, the times from the assignment of a score of 4 to a score of 6 were similar in the two groups (5.7 and 5.4 years, P=0.74). The time course of progressive, irreversible disease among patients with the primary progressive type of multiple sclerosis was not affected by the presence or absence of superimposed relapses. CONCLUSIONS: Among patients with multiple sclerosis, relapses do not significantly influence the progression of irreversible disability.

Adolescent↗

[Disease-modifying treatments in multiple sclerosis].

The number of available disease-modifying agents in multiple sclerosis has been increasing dramatically since 1993. First, interferon beta-1b has been licensed for exacerbating-remitting forms. Then, efficacy has been demonstrated for intramuscular or subcutaneously administered interferon beta-1a in the same indication. More recently, utility of interferon beta-1b in secondary progressive forms has also been proved. Concomitantly, with glatiramer acetate, the concept of a specific intervention on myelin auto-reactive T-cells been validated. Lastly, the classical approach of a global immunosuppression is still of interest. A better utilization of the currently available medications, an improvement of their efficacy/tolerance ratio, the exploration of new concepts such as neuro-protection and remyelination may soon lead to more significant advances.

Glatiramer Acetate↗

[Intramedullary tuberculoma: a case report].

A fifty-year-old Portuguese man presented with a six-month history of low back pain, which initially was mechanical and slowly became inflammatory. Secondarily, he complained of right atypical sciatalgia. He did not report any fever, loss of weight, cough nor personal or familial history of tuberculosis. General examination was normal. Neurologic examination showed weakness of the extensors of the right leg, with a symmetric increased reflexes of the lower extremities suggesting a pyramidal syndrome without Babinski's sign. Laboratory data were normal as well as chest radiographs. Dorsolumbar gadolinium enhanced MRI revealed an intramedullary ringlike enhancing mass at T12 level. Lumbar puncture showed 11 WBC/mm3 (95 p. 100 lymphocytes), a normal protein and glucose content. PCR and culture for Mycobacterium tuberculosis were negative. Within a few days, he developed meningoencephalitis with fever, CSF examination revealed then 360 WBC/mm3 (65 p. 100 lymphocytes and 17 p. 100 neutrophils), a protein content of 7 g/l and a glucose level of 1.7 mmol/l. The clinical picture was then suggestive of tuberculosis and a specific therapy with rifampin, izoniazid, pyrazinamid, ethambutol and steroids was started. Clinical improvement and a second CSF culture that revealed one month later Mycobacterium tuberculosis complex confirmed this diagnosis. Ten months later, the patient was asymptomatic with a normal MRI. To our knowledge, this is the first total recovery of an intramedullary tuberculoma on medical therapy alone, confirmed by MRI normalization. We reviewed also 19 recent cases of tuberculomas in the literature, intending a therapeutic attitude when discovering an intramedullary ringlike enhancing mass on MRI.

Antitubercular Agents↗

[Is it possible to predict the evolution of multiple sclerosis?].

Three characteristic features describe our understanding of the clinical course and outcome in multiple sclerosis: a validated statistical model of disease progression, wide interindividual variability, and a fixed rate of progression in an individual patient. However for and individual patient, it is still impossible to derive a precise and exact prediction of disease outcome, the only reliable method is the deterministic approach developed by Fog and Linneman in 1970 which consists in objective quantitative neurological examinations performed at three month intervals over several years in the same patient. In routine practice, this method in rather unrealistic. Bran MRI data with conventional techniques are also poorly discriminant. Conversely, it may be anticipated that new magnetic resonance techniques, more sensitive to axonal loss, demyelinization and gliosis, will provide reliable answers to this issue upon which therapeutic decisions depend.

Disease Progression↗

[Nicotine and worsening myasthenia].

We report a case of myasthenia gravis worsened by a nicotine transdermal system, in a man who usually was smoking fourty cigarettes per day without any worsening of his symptomatology. He noted an increased bilateral ptosis, total ophtalmoplegia, difficulty in chewing and generalized weakness two hours after application of a nicotine transdermal system, the symptoms improving after he removed it. Cholinergic receptors involved in myasthenia gravis are nicotinergic, and their number at the neuromuscular junction is reduced in myasthenia gravis. That leads to a "functional overdosage" after application of the nicotine transdermal system similar to the cholinergic crisis. This case can be compared with myasthenia syndromes described during the Second World War in tobacco chewers without any muscle impairment.

Administration, Cutaneous↗