Single nucleotide polymorphism and production of IL-1ß and IL-10 cytokines in febrile seizures.

Inflammation and genetics may play a role in the pathogenesis of febrile seizures. The aim of this study was to investigate the spontaneous and lipopolysaccharide (LPS)-induced production of IL-1ß and IL-10, and the association between IL-1ß (-511) and IL-10 (-1082) single nucleotide polymorphisms with LPS-induced cytokine production. The study included 92 febrile seizure patients and 132 healthy controls. First, we isolated genomic DNA and by using PCR-RFLP we genotyped the individuals for the cytokines gene polymorphism. Second, peripheral mononuclear cells of the individuals were isolated and stimulated with LPS to measure secretion capacity of IL-1ß and IL-10 using specific ELISA kits. We found that both the IL-1ß and IL-10 production was increased in febrile seizures. The rapid increase of IL-1ß production in the supernatants of the LPS-induced cells was significantly higher at the fourth and the twenty-fourth hours in febrile and complex febrile seizures, respectively. The distribution of IL-10 (-1082) G allele differs significantly between cases and controls. The IL-1ß (-511) G/A and the IL-10 (-1082) G/A genotype combination was found to be higher in patients with febrile seizure. Our results showed that IL-1ß and IL-10 production was not influenced by the single nucleotide polymorphisms in the pathogenesis of febrile seizures.

Unilateral nevoid telangiectasia accompanied by neurological disorders.

BACKGROUND: Unilateral nevoid telangiectasia (UNT) is a unique vascular dermatosis of ambiguous aetiology. OBJECTIVE: To investigate the role of neurological disorder in pathogenesis of the UNT. METHODS: We investigated eight consecutive patients with unilateral nevoid telangiectasia. Detailed dermatological and neurological examinations, and magnetic resonance imaging were performed on each patient. In case of presence of dysesthesia over the skin lesion, electroneuromyography was performed to determine any relationships between lesions and peripheral neuropathy. RESULTS: All the patients had hypoesthesia over the skin lesion. The cranial magnetic resonance imaging showed subcortical hamartomatous lesions in one patient and demyelinized plaques on the corpus of the caudate nucleus and the pontin area in another. Electroneuromyography evaluation was nonspecific. CONCLUSION: In our study, neurological disorders were associated with UNT. Thus, it can be speculated that neurological disorders might contribute to the development and/or progression of UNT. Patients with UNT should be encouraged for neurological investigation.

RLIP76 Gene Variants are not Associated with Drug Response in Turkish Epilepsy Patients.

Approximately 30% of epileptic patients remain untreated, in spite of trials with maximum tolerable doses of more than one drug. The RalA binding protein 1 (RALBP1/RLIP76), a multifunctional, anti-apoptot-ic, multidrug transporter protein, has been proposed as being responsible for the drug resistance mechanism in epilepsy. We have investigated polymorphic differences in the coding regions and exonintron boundaries of the RLIP76 gene, between 146 refractory and 155 non refractory epileptic patients in Turkey, using denaturing high performance liquid chromatography (HPLC) and sequencing analysis techniques. We have detected the following sequence variants: c.160-4G>A, c.187C>G, c.1562-38G>A, c.1670+107G>A, c.1670+93G>A, c.1670+96G>A, c.1670+100C>T, c.1670+130C>T, c.1670+131G>C, c.1670+140 G>C, and found no statistically significant correlation between allele frequencies and drug response status. We conclude that sequence variants of this gene are not involved in drug resistance in epilepsy.

Assessment of citrullinated myelin by 1H-MR spectroscopy in early-onset multiple sclerosis.

BACKGROUND AND PURPOSE: Myelin instability and citrullinated myelin basic protein have been demonstrated in the brains of patients with chronic and fulminating forms of multiple sclerosis (MS). Our aim was to trace citrulline in the brains of patients with early-onset MS by using proton MR spectroscopy ((1)H-MR spectroscopy). MATERIALS AND METHODS: A short-echo single-voxel (1)H-MR spectroscopy by using the point-resolved proton spectroscopy sequence was performed in 27 patients with MS and 23 healthy subjects. Voxels of interest were chronic demyelinating lesions (CDLs, n = 25) and normal-appearing white matter (NAWM, n = 25) on T2-weighted imaging, and when available in patients with MS, enhancing demyelinating lesions (EDLs, n = 8). Frontal white matter (WM) was studied in control subjects. N-acetylaspartate, choline, and myo-inositol (mIns)-creatine (Cr) ratios and the presence of a citrulline peak were noted. RESULTS: Citrulline peaks were more frequently observed in patients with MS than in control subjects (P = .035), located in the NAWM in 8/25 (32%), in CDLs in 7/25 (28%), and in EDLs of 1/8 (12.5%) patients with MS. The presence of citrulline and measured metabolite/Cr ratios was not related to age at imaging, age at disease onset, duration of disease, or number of relapses. There was no significant metabolic difference between the NAWM of patients with MS and the WM of the control subjects. mIns/Cr was significantly greater in CDLs compared with the NAWM of patients with MS and the WM of healthy subjects. CONCLUSIONS: Citrulline was more frequently identified in the brains of patients with early-onset MS than in healthy subjects by (1)H-MR spectroscopy, suggesting an association of increased citrullination of myelin proteins with demyelinating diseases.

Molecular analysis of fragile X syndrome in Antalya Province.

BACKGROUND: Detection of the (CGG)n repeats in the FMR1 gene that cause the fragile X syndrome (FXS), has become a milestone for phenotype-genotype correlation in FXS. AIMS: To screen the FMR1 gene CGG repeats in index cases with FXS and their family members in the Antalya Province. SETTING AND DESIGN: This study was prospectively conducted between January 2000 and March 2005 in Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, Antalya. MATERIALS AND METHODS: A series of 132 cases from three hospitals in Antalya Province were studied. All cases were molecularly screened using non-radioactive Expand Long PCR method that was confirmed by Southern blotting. RESULTS: Seventeen out of 132 cases were found to have a full mutation, including three that were mosaic for premutations/full mutations. Of the 132 cases, eight were found to have the premutation size of the CGG repeats. The remaining 107 cases were identified as normal. CONCLUSIONS: Due to premature ovarian failure and Fragile X premutation Tremor/Ataxia Syndrome related with the premutation, the detection of the premutation will provide valuable information both for clinical follow-up and genetic counseling. In conclusion, our data suggest that expansion of CGG repeats in the FMR1 gene can be analyzed by Expand Long PCR, an efficient and non-radioactive method that can be used to monitor the expansion of premutation to full mutation, which would eventually lead to reduce the FXS prevalence.

Acute disseminated encephalomyelitis in children: outcome and prognosis.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is the most common demyelinating disorder of childhood. Its clinical features, prognosis and treatment vary in different reports. OBJECTIVES: To examine a series of children with ADEM for clinical findings, course, recurrences, and possible variables affecting outcome. METHODS: Multicentric data collected from 7 tertiary referral centers were registered and evaluated in a central database in 1990 - 2001 for clinical, laboratory, and MRI features. Course and prognosis were assessed in patients with at least 12 months' follow-up. RESULTS: Forty-six patients were evaluated. Median age at onset was 8 years, M/F ratio, 1.7/1. Most common symptoms and signs pertained to the motor system and consciousness. Of 39 children with 12 months' follow-up, 71 % recovered completely. Thirteen (33 %) children had relapses. Patients who had more than one relapse (n = 4) presented with new symptoms at each attack. Treatment with high-dose methylprednisolone was associated with complete recovery, and tapering over more than 3 weeks, with a lower rate of relapses. MRI lesions could persist even in asymptomatic patients; in particular, periventricular lesions tended to disappear later than others. CONCLUSIONS: Complete clinical recovery is common and serious complications are rare in childhood ADEM, but the rate of relapses is considerable. Clinical picture at first relapse may help to identify patients likely to experience multiple relapses. The timing and duration of steroid treatment affects outcome.

Changing epidemiological features of subacute sclerosing panencephalitis.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a chronic central nervous (CNS) system infection caused by measles virus. Because changing immunization practices affect the epidemiology of measles and consequently SSPE, we examined the epidemiological data of our SSPE registry. MATERIALS AND METHODS: Age of onset, age at onset of measles, duration of Latent period and immunization status were examined in cases recorded at the SSPE Registry Center in Turkey between 1975 and 1999. RESULTS: Age of onset diminished from 13 years before 1994 to 7.6 years after 1995; age at onset of measles declined from 29 months to 20 months and the Latent interval from 9.9 years to 5.9 years. Age at onset of measles and immunization status did not directly affect the duration of the Latent period. CONCLUSION: Although its incidence has decreased in Turkey, SSPE has been seen at younger ages in recent years. This change cannot be attributed solely to younger age at onset of measles. Factors affecting the duration of the Latent period should be investigated further.

Interleukin-1beta, interleukin-1 receptor antagonist levels in patients with subacute sclerosing panencephalitis and the effects of different treatment protocols.

Subacute sclerosing panencephalitis is a rare progressive inflammatory disease of the central nervous system caused by a persistent aberrant measles virus infection. Cytokines are polypeptides that regulate immune responses and inflammatory reactions. Interleukin-1beta has been implicated as a central mediator of tissue damage and destruction in a number of central nervous system diseases. Interleukin-1 receptor antagonist could function as an important anti-inflammatory cytokine. We studied interleukin-1beta and interleukin-1 receptor antagonist levels in the cerebrospinal fluids of patients with subacute sclerosing panencephalitis and evaluated the effects of different treatment protocols on these cytokines. Interleukin-1beta and interleukin-1 receptor antagonist levels were measured in 15 patients who had a recent diagnosis of subacute sclerosing panencephalitis (group 1), 6 patients who had been treated with isoprinosine (group 2), 5 patients with intraventricular interferon-alpha (group 3), and 6 patients with interferon-beta (group 4). The results were compared within the groups and also with the results of 10 patients with other neurologic disease (group 5). The interleukin-1beta concentrations in cerebrospinal fluid and sera were all below the detection limits (3.9 pg/mL). Interleukin-1 receptor antagonist levels were not statistically different, except for the group treated with intraventricular interferon-alpha. Interleukin-1 receptor antagonist levels were 170 +/- 52, 175 +/- 58, 1605 +/- 518, 77.5 +/- 24, and 108 +/- 18 pg/mL in groups 1 to 5, respectively. Interleukin-1 receptor antagonist levels and cerebrospinal fluid serum ratios were significantly increased during interferon-alpha treatment. In conclusion, interleukin-1 and interleukin-1 receptor antagonist levels were not elevated in the patients with subacute sclerosing panencephalitis. The only treatment protocol that affects interleukin-1 receptor antagonist levels in cerebrospinal fluid was intraventricular interferon-alpha. Further studies on higher numbers of patients may better document the immunologic status of patients with subacute sclerosing panencephalitis and the effects of different treatment modes.

Subacute sclerosing panencephalitis: brain stem involvement in a peculiar pattern.

The most common pattern in subacute sclerosing panencephalitis, is in the cerebral hemisphere white matter on T2-weighted images with or without atrophy. Brain-stem lesions are rare. We report brain-stem involvement in two children with subacute sclerosing panencephalitis. A peculiar pattern, with involvement of the pons with extension to both middle cerebellar peduncles and substantia nigra but sparing the pontine tegmentum, is suggested.