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Biomedical subjects

Z Lević

Publications and source records attributed to Z Lević.

At least 19 recordsLinked to original sources

Primary progressive multiple sclerosis: clinical and paraclinical characteristics with application of the new diagnostic criteria.

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.

Adult↗

Uric acid levels in sera from patients with multiple sclerosis.

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.

Adolescent↗

Raised cerebrospinal fluid nitrite and nitrate levels in patients with multiple sclerosis: no correlation with disease activity.

A growing body of evidence implicates excessive generation of nitric oxide (NO) within the central nervous system (CNS) in multiple sclerosis (MS). The aim of our study is to analyse nitrite and nitrate as end products of NO in the cerebrospinal fluid (CSF) from MS patients and correlate the concentrations with clinicol characteristics of the disease. CSF nitrite and nitrate concentrations were measured after reduction of nitrate, by Griess reaction, in 105 MS potients, 27 patients with non-inflammatory neurological disorders (NIND) and 13 individuals without neurological disorder (Co). Mean CSF nitrite and nitrate concentrations were significantly higher in patients with MS and NIND compared with the Co patients (9.44 and 8.68, respectively, versus 6.85 microM; P=0.0001 and P=0.031, respectively). There was no significant correlation between CSF nitrite and nitrate concentrations and activity, phase, severity and duration of MS. Our data are in agreement with the results of previous studies which have demonstrated raised concentrations of CSF NO metabolites in MS patients, providing further evidence for NO involvement in MS. The lack of correlation between NO metabolites and disease activity speaks in favour of the possible dual role of NO, as both immunoregulatory and pro-inflammatory molecule, in the pathogenesis of MS.

Adolescent↗

Serum interleukin-12 levels in patients with multiple sclerosis.

Increasing body of evidence which suggests a crucial role for interleukin (IL)-12 in modulating immune responses in multiple sclerosis (MS) prompted us to analyze IL-12 in serum from MS patients. We measured the sera concentrations of IL-12, tumor necrosis factor (TNF)-alpha and transforming growth factor-beta1, in 21 MS patients and 13 patients with non-inflammatory nervous diseases. In clinically active MS, serum levels of IL-12 were detectable in 53% and TNF-alpha in 40% of patients. None of the patients with clinically inactive MS had detectable IL-12 and TNF-alpha sera levels. Analysis of serum concentrations of all three cytokines revealed no significant differences between MS patients and controls. These findings provide further evidence that both IL-12 and TNF-alpha might have an active role in immunopathogenesis of MS.

Adult↗

Unusual association of multiple sclerosis and tomaculous neuropathy.

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 lambda 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.

Adult↗

The effects of high-dose intravenous methylprednisolone on event-related potentials in patients with multiple sclerosis.

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.

Acoustic Stimulation↗

Interleukin-12 and tumor necrosis factor-alpha levels in cerebrospinal fluid of multiple sclerosis patients.

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 (P < 0.05). 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 (P < 0.05); 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.

Adult↗

A 44-month clinical-brain MRI follow-up in a patient with B12 deficiency.

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.

Brain↗

Short-term high dose steroid therapy does not affect the hypothalamic-pituitary-adrenal axis in relapsing multiple sclerosis patients. Clinical assessment by the insulin tolerance test.

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.

Adrenocorticotropic Hormone↗

The possible role of prolactin in the immunopathogenesis of multiple sclerosis.

Multiple sclerosis is a disease of the central nervous system characterized by multiple areas of inflammation and demyelination in the white matter of brain and spinal cord. A complex mechanism of the immunopathogenesis of the disease involves mononuclear cells infiltrating multiple sclerosis plaques, as well numerous cell products, such as interleukins, interferons, certain growth factors, etc. Some recent studies have emphasized the immunoregulatory role of certain neuroendocrine peptides, including prolactin. Prolactin, a hypophyseal hormone which is also produced by activated immunocytes, has been considered in this work as a co-factor participating in the immunopathogenic mechanism of multiple sclerosis.

Central Nervous System↗

[The clinical picture of Lyme disease in neurology].

Neuroborreliosis of central and peripheral nervous system was found in 24 patients with typical and atypical clinical syndromes. Information about tick bite was obtained in only 1/3 of our patients. Specific antibodies were found in 3/4 by flourescent antibody test, oligoclonal bands in 1/2, and signs of inflammation in cerebrospinal fluid in 1/3 of patients. The majority had favourable reaction to antibiotic therapy. It is necessary to investigate every case of suspected neuroborreliosis because it can imitate many neurological diseases. One must insist on information about the tick bite and/or erythema migrans and search for specific antibody production, both in blood and cerebrospinal fluid.

Adolescent↗

[Chronic encephalomyelitis caused by Borrelia burgdorferi. Case report].

We present a female patient with typical third stage neuroborreliosis with progressive chronic encephalomyelitis. One month after a tick bite, in the first stage of Lyme disease, she had myalgias during ten days and after one year polyarthralgias and polyarthritis. Neurological problems occurred 15 years after the tick bite with headache, nystagmus, intentional tremor and spastic paraparesis with sphincter disturbances. Etiological diagnosis was established after three years. Cytobiochemical findings in cerebrospinal liquor were normal but oligoclonal IgG bands were found. Fluorescent antibody test was positive in serum (1:75) as well as ELISA (1:447). The patient reacted favourably to intravenous crystal penicillin 20 x 10(6) units daily during 18 days. Till now, she is in remission and has only mild paresis of the left leg.

Adult↗

[Rhombencephalitis as a manifestation of neuroborreliosis].

Rhombencephalitis is a rare neurological manifestation of stage II of Lyme disease. We presented two cases with no recollection of tick bite nor erythema migrans and with cranial nerve nuclei, pyramidal tract and cerebellar tracts involvement of sudden onset, inflammatory syndrome in cerebrospinal liquor, positive oligoclonal bands and elevated IgG index. A spontaneous remission occurred in both cases, but antibiotic was given intravenously for prevention of relapses and disease progression.

Encephalitis↗

Tooth pulp evoked potentials (TPEPs) in multiple sclerosis patients.

The purpose of this study was to determine possible changes of the tooth pulp evoked potentials in patients with multiple sclerosis, and to compare these with other types of evoked potentials, in the same patients. The results showed TPEP changes in all multiple sclerosis patients. In 12 patients the changes were observed on both sides, while in 6 on one side only. It is interesting to note that the second negative wave was characterized by two peaks. The first peak possessed latency of approximately 125 ms that was significantly shorter than in the control group. The second peak appeared after about 195 ms. The significant prolonged latency of the second negative wave was observed in 100% of TPEPs, 95% VEPs and 72% AEPs. In only one case the changes were observed in TPEPs, while VEPs and AEPs were normal. It could be concluded that TPEPs, as well as other types of evoked potentials, are a sensitive indicator of the demyelination process.

Adolescent↗

Single dose and steady state pharmacokinetics of valproic acid in adult epileptic patients.

The pharmacokinetics of valproic acid was studied in ten adult epileptic patients (five f + five m, 19-48 years; 28 +/- 12, mean +/- SD, and body mass 45 to 70 kg; 61 +/- 7, mean +/- SD) both after single dose and at the steady state. Sodium valproate was given in a 900 mg single oral dose on the first day of therapy, followed by 3 x 300 mg/day during the three subsequent days (at the intervals of 7, 8 and 9 h). During the first day, plasma was obtained just before the drug was given, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 h after drug administration. On the fourth day of therapy (at steady state), plasma was obtained just before the next dose and 3 h after the drug administration. The plasma concentrations of valproic acid were measured by gas chromatography with flame ionization detection, after extraction with chloroform. The pharmacokinetic parameters, necessary to define the pharmacokinetics of valproic acid, were calculated both after single dose: Cmax, tmax, kel, t1/2, Vd, AUC and Cl, and at steady state: Cminss Cmaxss and Fl%. These parameters, as well as plasma levels of the drug, were used to describe the pharmacokinetic behaviour of valproic acid under these clinical conditions, and mainly were in agreement with the values published in the literature.

Administration, Oral↗

The disturbance of nonverbal functions in dysphasia.

Various modalities of six neuropsychological functions (graphia, calculia, finger gnosis, right-left orientation, praxia and constructive praxia) referred to as parietal or nonverbal have been investigated in the light of speech disorders. We examined 20 patients with brain lesion of vascular origin, who met the diagnostic criteria of mild and moderate dysphagia, 13 patients with Wernicke's and 7 with Broca's dysphasia. Verbal and nonverbal functions in patients with ischemic focuses of the speech area of the left hemisphere were investigated the Boston Diagnostic Aphasia Examination (BDAE). The investigation revealed that the presence and the type of mild and moderate dysphasia had a noteworthy role in pathoplasticity of correlated signs, thus implying in clinical practice a parietal lesion. Generally, poorer and at the same time more heterogeneous results were obtained in patients with Wernicke's dysphasia, mostly on calculia and right-left orientation. Finger agnosia was not considered as an authentic parietal sign, while each modality of graphia was impaired to a varying extent in speech disorders caused by presylvian and retrosylvian lesions. The paper also deals with the significance of lobulus parietalis inferior in speech.

Aphasia↗