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Background: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system, commonly attributed to infections or vaccinations. Toxic or allergenic compounds can also trigger a response in the immune system and may cause demyelination. We present a case with ADEM after using oral herbal medications. Case Report: A 25 year-old male developed bilateral central facial palsy and severe quadriparesis after taking herbal drugs (containing echinacea and many other herbal ingredients) for two weeks. He had used the extract to increase his potency and reproductivity. He had no past history of recent immunization or viral infection. The clinical findimethylprednisolone treatment. To our knowledge, this is the third report in the literature that links herbal therapy and demyelinating disease. Conclusion: Most of the ADEM cases related to herbal therapy in the literature similarly used echinacea. It is our opinion that other ingredients of the herbal extract used by our case, besides echinacea, could have the potential to cause a trigger in the immune system. Further studies are needed to clarify the immunological effects of different kinds of herbal compounds, as well as the effects of different parts of the plants and the results of various dosages. Moreover, ingredients should also be tested for toxicity, adverse effects and drug interactions.ngs, cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) were compatible with ADEM. The neurological findings were improved after seven doses of pulse [ABSTRACT FROM AUTHOR]

Background and Purpose: Multiple Sclerosis (MS) can be accompanied by autonomic dysfunction which has an important impact on the disability. The aim of this study was to compare the frequency of autonomic abnormalities in MS patients and controls using standard autonomic tests and heart rate variability. It was also aimed to seek any relationship between cranial and cervical spinal magnetic resonance imaging (MRI) findings with autonomic tests and heart rate variability. Methods: Twenty-four (68.6%) relapsing-remitting, eleven (31.4%) secondary progressive MS patients and 21 age matched controls were enrolled in the study. All subjects underwent standard autonomic function tests assessing parasympathetic (heart rate responses to Valsalva maneuver, deep breathing, and active change of posture) and sympathetic function (blood pressure responses to active change of posture) as well as heart rate variability analysis both for a 24-hour period and during tilt testing using Holter monitoring. To assess the relationship between autonomic abnormalities and MRI all the patients underwent cranial and cervical spinal MRI. Results: Our results showed that MS patients have decreased heart rate variability and diminished parasympathetic component of autonomic nervous system compared to controls. No significant association has been found between autonomic impairment in MS and the type and duration of the disease. There has been no significant relationship between MRI findings and autonomic involvement in MS. Conclusion: MS patients have autonomic dysregulation against parasympathetic component, a condition which has no significant relationship with cranial and cervical spinal MRI findings. [ABSTRACT FROM AUTHOR]

We, herein, report a 23-year-old male with a rare inherited immunodeficiency disease, hyperimmunoglobulin IgE syndrome (HIES), who developed progressive multifocal leukoencephalopathy (PML) and lymphoma simultaneously. Primary immunodeficiency of the patient has remained undiagnosed until adulthood. PML is a severe demyelinating disease of the central nervous system caused by John Cunningham virus. HIES is a rare, inherited immunodeficiency characterized by high serum levels of IgE, recurrent staphylococcal infection, eczema, and hypereosinophilia. PML may accompany primary immunodeficiency syndromes, but the association with HIES is exceedingly rare. We discuss the imaging findings, medical management, and a review of related literature on primary immunodeficiency cases complicating with PML. [ABSTRACT FROM AUTHOR]

Abstract: Reliable, and easy to measure, immunological markers able to denote disease characteristics in multiple sclerosis (MS) patients are still lacking. We applied a multivariate statistical analysis on results obtained by measuring–by real-time RT-PCR–mRNA levels of 25 immunological relevant molecules in PBMCs from 198 MS patients. The combined measurement of mRNA levels of IL-1β, TNF-α, TGF-β, CCL20 and CCR3 was able to distinguish MS patients from healthy individuals. CXCR5, CCL5, and CCR3 combined mRNA levels identify primary progressive MS patients while TNF-α, IL-10, CXCL10 and CCR3 differentiate relapsing MS patients. Our results indicate that multi-parametric analysis of mRNA levels of immunological relevant molecules in PBMCs may represent a successful strategy for the identification of putative peripheral markers of disease state and disease activity in MS patients. [Copyright &y& Elsevier]

Definitions and measures of asthma control used in clinical trials and practice often vary, as highlighted in the manuscript, "Is asthma control more than just an absence of symptoms? An expert consensus statement". Furthermore, the authors discussed differences between patients and healthcare professionals (HCPs) in terms of understanding and managing asthma. Given these disparities, there is a need for consensus regarding what constitutes well-controlled asthma and, especially, how best it can be measured and recorded. In the current work, we describe our data and provide more detail on the methodology from a two-stage Delphi survey and a structured literature review, which were designed to reach a consensus definition of asthma control and alleviate misalignments between patients and HCPs. Survey data were collected using a two-stage Delphi technique; a method used to collate expert opinions over a series of sequential questionnaires to reach a consensus. The collated Delphi survey data were compared with results from a comprehensive, structured literature review of 216 publications, to assess if there was a correlation between existing guidance and measures of asthma control used in clinical trials and standard clinical practice. In order to collate and interpret findings from the Delphi survey, responses from 82 panelists (73 HCPs and 9 authors) were qualitatively analyzed, quantitatively categorized, and presented as percentages or counts in Excel databases, which are detailed in the current work. Searches conducted using PubMed and Cochrane identified 664 manuscripts, and Embase was used to identify 89 congress abstracts. After applying a stringent screening method using predefined key words, the structured literature review consisted of 185 peer-reviewed manuscripts and 31 congress abstracts, and assessed existing guidance and measures of asthma control used in clinical trials. In this publication, we provide further insight into the predefined keywords, search strings, and strategy applied to identify manuscripts and congress abstracts for inclusion/exclusion, and detail methods for data extraction. Together, the data from the Delphi survey and structured literature review aimed to provide greater insights into challenges and approaches in achieving asthma control in clinical practice, with the potential for results to be used to guide a universally accepted definition and measure of asthma control that can be used and understood by patients, HCPs, and researchers. Qualitative and quantitative methodology and analysis from the Delphi survey and literature review search strategy can potentially be used to identify disparities and explore expert opinion and relevant literature in other therapeutic areas to guide a consensus where disparities exist., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A. Spanevello reports consulting fees from GSK; payment or honoraria from AstraZeneca, Chiesi, and GSK; and participation on a data safety monitoring board or advisory board for GSK. L. Pérez de Llano reports grants or contracts from AstraZeneca, Esteve, FAES Pharma, and Teva, consulting fees from AstraZeneca, GEBRO, Gilead, GSK, MSD, Novartis, and Sanofi; payment or honoraria from AstraZeneca, Chiesi, Esteve, GSK, LEO Pharma, MSD, Novartis, and Sanofi; support for attending meetings and/or travel from AstraZeneca, Chiesi, FAES Pharma, GSK, and Novartis; and participation on a data safety monitoring board or advisory board for AstraZeneca. C. Domingo Ribas has received funding for travel or speaker fees from ALK, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GSK, Menarini, Novartis, Pfizer, and Stallergenes, and declares no specific conflicts of interest to report regarding this paper. J.D. Blakey reports grants or contracts from AstraZeneca, GSK, and Novartis; consulting fees from Boehringer Ingelheim, Chiesi, and GSK; payment or honoraria from AstraZeneca, Chiesi, and GSK; support for attending meetings and/or travel from AstraZeneca, Boehringer Ingelheim, and GSK; receipt of medical writing support from GSK and Teva; payment to their institution for advisory work from Asthma Australia; and unpaid advisory work from Asthma WA. H. Inoue declares research grants from Boehringer Ingelheim, payment or honoraria for lectures and advisory committees from AstraZeneca, Boehringer Ingelheim, GSK, Kyorin, Novartis, and Sanofi. G.W. Canonica declares no conflict of interest for the current paper, and reports having received research grants as well as being lecturer or having received advisory board fees from A.Menarini, Allergy Therapeutics, Anallergo, AstraZeneca, Chiesi, FAES Pharma, Firma, Genentech, GSK, Guidotti-Malesci, Hal Allergy, Innovacaremd, Novartis, OmPharma, RedMaple, Sanofi-Aventis, Sanofi-Genzyme, Stallergenes-Greer, ThermoFisher, Uriach Pharma, and Valeas. D. Yang, and M. Dalcolmo declare that they have no disclosures of interest. G. Garcia declares participation in advisory boards for AstraZeneca, Boehringer Ingelheim, GSK, Novartis, and Sanofi; participation in sponsored activities for AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Sanofi, and Phoenix; principal investigator for AstraZeneca, Boehringer Ingelheim, Chiesi, Covance, GSK, Iqvia, Novartis, Parexel, PPD, Sanofi, and Zambon. S. Mokashi, A. Kurne, and A. Butta were GSK employees at the time of study conduct and hold shares in GSK., (© 2023 Published by Elsevier Inc.)

Purpose: Definitions and measures of asthma control used in clinical trials and in clinical practice vary considerably. There is also misalignment between patients and healthcare professionals (HCPs) in terms of understanding and managing asthma control. This study aimed to progress towards a consensus definition of asthma control, and evaluate disparities between HCP and patient perspectives., Basic Procedures: A two-stage Delphi questionnaire involving asthma specialists sought to identify areas of consensus on aspects of asthma control in clinical practice. Results were compared with those of a structured literature review to assess if existing guidance and measures of asthma control used in studies correlated with practice. Eighty-two panelists took part in the Delphi questionnaire. The structured literature review included 185 manuscripts and 31 abstracts., Main Findings: Panelists agreed that there was no standard definition of asthma control, confirmed by a total of 19 different composite consensus/guideline definitions and/or validated measures of control being identified across the Delphi study and literature review. Panelists agreed on the positive associations of well-controlled asthma with patient outcomes, but not on the components or thresholds of a working definition of control., Principal Conclusions: A universally accepted definition and measure of asthma control that is utilized and understood by patients, HCPs, and researchers is required., (Copyright © 2022. Published by Elsevier Ltd.)

Background/aim: Neurological involvement (Neuro-Behcet's Disease: NBD) is a rare manifestation of Behcet's Disease (BD) and it is related with significant mortality and morbidity. We aimed to evaluate disease course and outcome of NBD patients registered in Hacettepe University Vasculitis Center (HUVAC) prospective database starting from October 2014., Methods: Totally, 419 patients (329 of the patients had fulfilled the International Study Group (ISG) criteria and 90 patients were considered as incomplete BD) were recorded as BD to March 2018. We retrospectively reviewed the charts of 123 patients with neurological complaints/ symptoms according International Consensus Recommendations (ICR) Criteria for Neuro-Behçet's disease. In final analysis, 77 NBD patients (Definite NBD = 61, possible NBD = 16) were included. Demographics, clinical features, treatment characteristics, disability status and survival status of the patients were evaluated., Results: Forty-seven (61%) of the patients were male. Median time to neurological involvement from first diagnosis of BD is 6 (IQR = 8.8) years in patients who had diagnosis of BD before neurological involvement. Distribution of NBD: parenchymal (pNBD), non-parenchymal (npNBD), mixed (mNBD) and peripheral nervous system (pnsNBD) were 47 (61%), 22 (28.6%), 5 (6.5%), 3 (3.9%), respectively. Eye involvement was more frequent in pNBD compared to npNBD. Brainstem (72.9%) was the most frequently affected parenchymal area and followed by cerebellum (43.8%) and diencephalon (37.5%). Twelve patients had spinal cord involvement (n = 12, 24.5%). Among the patients with pNBD and mNBD (total n = 52), 48 patients were considered as acute onset parenchymal disease and 4 patients were evaluated as chronic progressive disease. Fifty-eight percent of the patients with acute onset parenchymal disease had only one attack. Totally 14 BD patients deceased during a median 9.4 (IQR = 13) years disease duration and 9 of these patients had NBD (pNBD = 6, mNBD = 2, pnsNBD = 1). Corticosteroids (IV pulse = 75.5% and oral medium-high dose = 90%), alpha-interferon (76.9%), cyclophosphamide (57.1%), and TNF inhibitors (23.5%) were the most frequently preferred treatment options for pNBD., Conclusions: Neurological involvement is seen about 5 years after the diagnosis of BD, and ocular involvement more commonly seen in these patients than non-NBD patients. More than half of the patients with acute onset parenchymal NBD had only one attack. No death was observed in the patients with non-parenchymal NBD. Biologic agents (Interferon-alpha and anti-TNF agents) were used in most patients., Competing Interests: Declaration of Competing Interest The authors have received no financial support or other benefits from commercial sources for the work reported here, and the authors have no other financial interests that could create a potential conflict of interest or the appearance of a conflict of interest regarding the present study., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To identify circulating myelin oligodendrocyte glycoprotein (MOG)-specific B cells in the blood of patients with MOG antibodies (Abs) and to determine whether circulating MOG-specific B cells are linked to levels and epitope specificity of serum anti-MOG-Abs., Methods: We compared peripheral blood from 21 patients with MOG-Abs and 26 controls for the presence of MOG-specific B cells. We differentiated blood-derived B cells in vitro in separate culture wells to Ab-producing cells via engagement of Toll-like receptors 7 and 8. We quantified the anti-MOG reactivity with a live cell-based assay by flow cytometry. We determined the recognition of MOG epitopes with a panel of mutated variants of MOG., Results: MOG-Ab-positive patients had a higher frequency of MOG-specific B cells in blood than controls, but MOG-specific B cells were only detected in about 60% of these patients. MOG-specific B cells in blood showed no correlation with anti-MOG Ab levels in serum, neither in the whole group nor in the untreated patients. Epitope analysis of MOG-Abs secreted from MOG-specific B cells cultured in different wells revealed an intraindividual heterogeneity of the anti-MOG autoimmunity., Conclusions: This study shows that patients with MOG-Abs greatly differ in the abundance of circulating MOG-specific B cells, which are not linked to levels of MOG-Abs in serum suggesting different sources of MOG-Abs. Identification of MOG-specific B cells in blood could be of future relevance for selecting patients with MOG-Abs for B cell-directed therapy., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Susac's Syndrome (SS), which was first described in 1979, is a rare and presumably autoimmune disorder characterized by encephalopathy, hearing loss, and visual disturbance resulting from branch retinal artery occlusion (BRAO). This study reports 19 SS patients' clinical characteristics, MRI features, CSF analysis, treatment strategies and outcomes. At initial presentation, only three of 19 patients demonstrated the complete clinical triad. Clinic presentation varied from isolated hemiparesis to the full triad (encephalopathy, hearing loss and visual disturbances). Corpus callosum (CC) involvement was noted in the MRI of 18 patients (97%) and BRAO was detected in 17 (95%) patients. All patients were treated with intravenous methylprednisolone after the initial assessment. This case series is presented to emphasize the differences in clinical presentation of SS and the importance of MRI and FFA in diagnosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Autoantibodies to myelin oligodendrocytes glycoprotein (MOG) are found in a fraction of patients with inflammatory demyelination and are detected with MOG-transfected cells. While the prototype anti-MOG mAb 8-18C5 and polyclonal anti-MOG responses from different mouse strains largely recognize the FG loop of MOG, the human anti-MOG response is more heterogeneous and human MOG-Abs recognizing different epitopes were found to be pathogenic. The aim of this study was to get further insight into details of antigen-recognition by human MOG-Abs focusing on the impact of glycosylation. MOG has one known N-glycosylation site at N31 located in the BC loop linking two beta-sheets. We compared the reactivity to wild type MOG with that toward two different mutants in which the neutral asparagine of N31 was mutated to negatively charged aspartate or to the neutral alanine. We found that around 60% of all patients (16/27) showed an altered reactivity to one or both of the mutations. We noted seven different patterns of recognition of the two glycosylation-deficient mutants by different patients. The introduced negative charge at N31 enhanced recognition in some, but reduced recognition in other patients. In 7/27 patients the neutral glycosylation-deficient mutant was recognized stronger. The folding of the extracellular domain of MOG with the formation of beta-sheets did not depend on its glycosylation as seen by circular dichroism. We determined the glycan structure of MOG produced in HEK cells by mass spectrometry. The most abundant glycoforms of MOG expressed in HEK cells are diantennary, contain a core fucose, an antennary fucose, and are decorated with α2,6 linked Neu5Ac, while details of the glycoforms of MOG in myelin remain to be identified. Together, we (1) increase the knowledge about heterogeneity of human autoantibodies to MOG, (2) show that the BC loop affects recognition in about 60% of the patients, (3) report that all patients recognized the unglycosylated protein backbone, while (4) in about 20% of the patients the attached sugar reduces autoantibody binding presumably via steric hindrance. Thus, a neutral glycosylation-deficient mutant of MOG might enhance the sensitivity to identify MOG-Abs.

Background: Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology., Objectives: To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline., Methods: Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner., Results: Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results., Conclusion: In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: Cigarette smoking has been associated with increased occurrence of multiple sclerosis (MS), as well as clinical disability and disease progression in MS. We aimed to assess the effects of smoking on the white matter (WM) in patients with clinically isolated syndrome (CIS) using diffusion tensor imaging., Methods: Smoker patients with CIS (n=16), smoker healthy controls (n=13), nonsmoker patients with CIS (n=17) and nonsmoker healthy controls (n=14) were included. Thirteen regions-of-interest including nonenhancing T1 hypointense lesion and perilesional WM, and 11 normal-appearing white matter (NAWM) regions were drawn on color-coded fractional anisotropy (FA) maps. Lesion load was determined in terms of number and volume of WM hyperintensities., Results: A tendency towards greater lesion load was found in smoker patients. T1 hypointense lesions and perilesional WM had reduced FA and increased mean diffusivity to a similar degree in smoker and nonsmoker CIS patients. Compared with healthy smokers, smoker CIS patients had more extensive NAWM changes shown by increased mean diffusivity. There was no relationship between diffusion metrics and clinical disability scores, duration of the disease and degree of smoking exposure., Conclusion: Smoker patients showed a tendency towards having greater number of WM lesions and displayed significantly more extensive NAWM abnormalities.

Anti-NMDA receptor encephalitis is a severe disorder characterised clinically by seizures, autonomic instability, and severe disturbances of memory, behaviour, and cognition. Due to the severity of symptoms, many patients are admitted to the intensive care unit. For some patients, the presence of various movement disorders and abnormal autonomic signs, as well as a history of seizures, lead to a false impression of status epilepticus, which is reported in 6% of the cases. Here, we present two young female patients, one of whom had ovarian teratoma. Both patients were referred to our neurological intensive care unit with a diagnosis of status epilepticus. However, prolonged video-EEG findings were compatible with encephalopathy. We avoided aggressive treatment with intravenous anaesthetics and both patients recovered after immunotherapy, one of whom received surgery. Physicians should be cautious in interpreting abnormal movements and autonomic signs in such patients and video-EEG monitoring is advised when status epilepticus is suspected. [Published with video sequences].

Soluble (s) CD14, being a receptor for lipopolysaccharides (LPSs) may inhibit LPS-triggered apoptosis and T lymphocyte proliferation. C to T exchange at position -159 in the promoter region of the CD14 gene might lead to higher sCD14 levels. Limited number of groups have studied whether these polymorphisms might influence the development of organ specific autoimmunity and whether higher CD14 levels are associated with increased levels of cytokines trigerring inflammatory processes. However their data contradict each other. In this study serum levels of sCD14 based on ELISA were measured in 77 treatment-naive patients and in 67 healthy controls. As the C-159T proximal promoter region regulates sCD14 levels, we investigated whether C-159T polymorphism is related to progression index in 250 MS patients vs. 183 healthy controls. CD14 polymorphism frequency between the healthy controls and the MS patients were not significantly different. While TT genotype of MS patients demonstrated significantly lower sCD14 levels compared to CC genotype; this difference was not reflected on the disease progression index. Our study that extends the prior data of previous studies reflects that sCD14 do not appear to be a solely prominent element of innate immunity in MS., (Copyright © 2012. Published by Elsevier B.V.)

Psoriasis was recently accepted as an autoimmune T cell-mediated disease. Various autoimmune disease associations for psoriasis have been defined, including multiple sclerosis, a model autoimmune demyelinating neurologic disorder. In this study, the familial frequency of psoriasis in a Turkish multiple sclerosis cohort was investigated, and a higher frequency of psoriasis was found, supporting the presence of a complex background of autoimmunity underlying psoriasis.

Objectives: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and B cell-activating factor (BAFF), the members of tumor necrosis factor superfamily, play essential roles in immune homeostasis and may have potential contributions to the autoimmune process in multiple sclerosis (MS)., Material and Methods: Thirty-five relapsing remitting MS (RRMS) patients and 19 healthy individuals were enrolled in the study. The expression of TRAIL on peripheral blood lymphocytes was analyzed by flow cytometry. The serum levels of soluble TRAIL (sTRAIL) and soluble BAFF (sBAFF) were determined by ELISA. Further, we evaluated the effect of IFN-β on sTRAIL, sBAFF levels and on TRAIL surface expression in these patients on the third and sixth months following the treatment., Results and Conclusion: These preliminary results signify that MS patients are heterogenous in TRAIL expression. Additionally, during the IFN-β treatment, the soluble form of TRAIL increases concomitantly as its surface expression decreases on lymphocytes. The basal sBAFF levels of patients were significantly higher than the control group and no significant change was observed. Thus, the changes in TRAIL expression may be a potential parameter indicating the response to IFN-β1 therapy at individual level., (Copyright © 2010 The Authors. Journal compilation © 2010 Blackwell Munksgaard.)

Patients with acquired immunodeficiency syndrome (AIDS) are the subjects of a large part of routine neuroradiological work in the Western world currently. The World Health Organization announced that Turkish authorities had reported a cumulative total of 2544 HIV cases from 1985 to 2006, of whom 623 had developed AIDS and 140 had died. It is estimated that approximately one-third of AIDS patients develop neurological complications. The spectrum of diseases affecting the central nervous system (CNS) in AIDS patients comprises predominantly opportunistic infections and primary CNS lymphoma. Although to a lesser degree when compared with Western countries, the incidence of AIDS and related neurological diseases are on the rise also in Turkey. Therefore radiologists should recognize HIV-associated problems and their imaging features. In this review, we focus on imaging features of more common CNS diseases in HIV-seropositive patients. This essay has been prepared using radiological studies of the patients who had been managed in our hospital which is a tertiary care center with a highly motivated medical team for this peculiar disease in the years between 2002 and 2008.

A more favorable clinical course in early-onset (EO) multiple sclerosis (MS) than adult-onset (AO) disease is reported. Our aim was to assess white matter with/without lesions by magnetization transfer (MT) imaging in EO and AO MS patients matched for duration of the disease. Relapsing-remitting MS patients with disease onset at age < or =18 years and >18 years (n = 11 for each) were matched according to sex, age, disease duration, and 22 sex-and age-matched healthy subjects were studied with MT imaging. MT ratios (MTR) of manually outlined ROIs from T1-hypointense, T1-isointense lesions and perilesional normal appearing white matter (NAWM) as well as NAWM of the left frontal lobe of the patients and healthy subjects were calculated. MTR differences between two patient groups and control subjects, and correlation of MTR with EDSS, disease onset age, disease duration and relapse rate were analyzed statistically. In comparison with NAWM of the patients and healthy subjects, the greatest MTR reductions were observed in T1-hypointense lesions followed by T1-isointense lesions and perilesional NAWM, respectively, in EO and AO MS. Both groups' NAWM MTR were reduced; greater and more significantly in EO patients. No correlation was found between MTR of any ROI and EDSS, duration of the disease, disease onset age, or relapse rate. Although normalization does not occur, abnormality of white matter in MS decreases as distance from the lesions increases. Greater NAWM abnormality in EO MS may relate to inherent myelin abnormalities and different repair/reorganization processes in this particular group.

We conducted this study to determine familial Mediterranean fever (FMF)-associated central nervous system involvement including demyelinating lesions, stroke, and posterior reversible leukoencephalopathy syndrome (PRES). Patients with MEFV mutations were systematically reviewed through the Medical Biology Unit database. All samples sent for mutation analysis were screened for 10 common MEFV mutations. Patients with FMF and neurologic disorders according to the clinical records were invited for reevaluation. Lumbar puncture, electroencephalography, and evoked potentials were used to determine the type of neurologic involvement in selected cases. Electrocardiography, transthoracic and/or transesophageal echocardiography, and magnetic resonance imaging and/or angiography were performed to clarify the etiology of cerebrovascular disease. Of 8864 patients in the genetic testing database, 18 with neurologic signs were assessed. The mean age of patients was 31.0 +/- 11.8 years, mean age at first FMF symptom was 12.6 +/- 5.6 years, and mean age at neurologic involvement was 25.8 +/- 12.2 years. Fifty-five percent of patients were women. A homozygote MEFV mutation was detected in 16 of 18 patients (88.8%), and a homozygote M694V mutation was found in 72.2% of patients. We found 7 FMF patients with demyelinating lesions, 7 with cerebrovascular disease, and 4 with PRES. The mean interval between first FMF sign and neurologic involvement was 13.7 +/- 8.9 years in the demyelinating group, and 23.4 +/- 10.3 years in the group with cerebrovascular disease. Mean stroke age was 28.5 +/- 16.4 years. All patients in the PRES group had hypertension. Three different neurologic conditions in FMF patients were noticeable. Demyelinating lesions and cerebrovascular disease were the most common clinical presentations. Approximately 70% of patients had the homozygote M694V mutation. Neurologic involvement is rare but serious in FMF.

Severe primary central nervous system (CNS) involvement such as vasculitis and pachymeningitis can rarely occur in rheumatoid arthritis (RA) even in the absence of systemic disease activation. The authors illustrate a female patient with well-controlled RA who presented with headaches, encephalopathy, seizures and relapsing focal neurological deficits. Primary rheumatoid cerebral vasculitis and pachymeningitis were diagnosed based on suggestive brain magnetic resonance (MR) imaging, MR angiography, cerebrospinal fluid analysis and cerebral angiography. MR showed abnormal leptomeningeal enhancement and hyperintense FLAIR signal in the cortical subarachnoid spaces consistent with pachymeningitis. Cerebral angiography findings were consistent with vasculitis. Aggressive treatment resulted in significant clinicoradiological resolution. Cerebral vasculitis is a rare but certain manifestation of RA. This complication can be diagnosed in the presence of suggestive angiographic and CSF findings. The condition may be steroid resistant, and needs to be treated more aggressively.

Background: Optic neuritis in children may be an isolated, usually postinfectious event, or the symptom of a more widespread disorder., Aim: To investigate the etiological spectrum of optic neuritis in children in association with diagnostic findings and follow-up results., Methods: We retrospectively examined the records of 31 children aged 4-15 (mean 9.7+/-2.9) years in whom isolated optic neuritis was the presenting neurological symptom., Results: Monophasic bilateral optic neuritis was the most common presentation (45%), followed by the unilateral (32%) and recurrent (22%) forms. Initial cranial MRI was abnormal in 12/31 patients. During a mean follow-up of 2.2 years (6 months-15 years), 6/14 bilateral cases, 9/10 unilateral and 5/7 recurrent cases were diagnosed with various disorders including total eight with MS. The MS group tended to start with unilateral optic neuritis, was older (mean 11.6+/-1.5 vs. 8.8+/-2.9 years), and included more girls than the other groups., Conclusions: Optic neuritis in children is frequently part of a systemic or neurological disorder even in the presence of normal cranial imaging. These patients should be evaluated and followed-up in pediatric neurology clinics.

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.

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations of a number of diseases such as multiple sclerosis (MS) and collageneous tissue disorders. In the present study, particular systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) patients, who were followed up with the initial diagnosis of possible MS with no evidence of collagen tissue disorders for several years, are described. Five patients with the final diagnosis of SLE and five pSS patients are evaluated with their neurologic, systemic and radiologic findings.Over several years, all developed some systemic symptoms like arthritis, arthralgia, headache, dry mouth and eyes unexpected in MS. During the regular and close follow-up laboratory evaluations of vasculitic markers revealed positivity, leading to the final definite diagnosis of SLE or pSS. Patients with atypical neurological presentation of MS, a relapsing remitting clinical profile, or lack of response to the regular MS treatment should be evaluated for the presence of a connective tissue disease. Various laboratory tests, such as cerebrospinal fluid findings, autoantibodies profile, markers, cranial and spinal magnetic resonance imaging, can be helpful for the differential diagnosis. Lack of response to the regular multiple sclerosis treatment, even increasing rate of relapses can force the clinician for the differential diagnosis. In particular cases an accurate diagnosis can only be made after close follow-up.

Isolated spinal accessory nerve (SAN) palsy is a well-recognized complication of surgical prodecures in the posterior triangle of the neck. Various rare etiological factors were also described. Whatever the etiology, the typical clinical features of SAN palsy can be listed as atrophy/weakness of the trapezius muscle and moderate winging of the scapula. It is imperative to promptly diagnose this condition in the early stage to avoid long-term impairment and to have a better functional outcome. Herein, we present a patient with a diagnosis of spontaneous spinal accessory nerve palsy, which was rarely reported in the relevant literature.

In patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), the most common cause of focal intracranial lesion is Toxoplasma gondii infection. T. gondii encephalitis is an easily and effectively treatable disease, with promising outcomes. T. gondii has the potential to form a focal infection niche anywhere in the central nervous system, thus allowing for a colorful clinical picture. In this report, we attempted to present five HIV/AIDS cases with central nervous system toxoplasmosis demonstrating five different neurological presentations. The ages, gender and clinical findings of the patients who were admitted to our Infectious Diseases Clinics were as follows; 35 years old male patient with delirium, 49 years old male patient with focal dystony, 32 years old female patient with facial paralysis and monoparalysis, 53 years old male patient with Wernicke syndrome, 32 years old male patient with epilepsy. Cerebral toxoplasmosis were diagnosed by clinical findings and imaging techniques. The patients were treated with trimetoprim-sulfametoxazol (TMP-SMZ) and haloperidol, only TMP-SMZ, clindamycin and daraprim, TMP-SMZ and levotiracetam, TMP-SMZ and phenytoin, respectively, with recovery in neurological and radiological symptoms. In conclusion, until proven otherwise, HIV/AIDS patients presenting with focal neurological complaints should be accepted as having central nervous system toxoplasmosis.

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive prion disease that causes deficits involving movement, cognition, and mental status. The clinical heterogeneity of the disease can make diagnosis difficult. Thorough neurologic, cognitive, and psychiatric examinations are necessary for observing its clinical features. In this case report we describe a 62-year-old male patient who was initially followed with a diagnosis of depression and later was diagnosed with CJD. The patient had a one-year history of anhedonia, loss of interest, social withdrawal, anxiety and decrease in speech and was given paroxetin 20 mg/day with a diagnosis of depression. During follow up, neurological symptoms including ataxia and rigidity became evident and dementia and akinetic mutism developed in a rapidly progressive course. Although electroencephalography (EEG) and magnetic resonance imaging (MRI) revealed nonspecific findings initially, typical findings for CJD were seen during the follow up. The positive 14-3-3 protein in CSF supported the diagnosis. The aim of this report is to emphasize the fact that CJD may present with different psychiatric symptoms and can be initially misdiagnosed. CJD should be considered in the differential diagnosis of patients who have focal neurological signs in addition to psychiatric symptoms. Repeated neurological examinations, EEG and cranial MRI may help in the diagnosis of these patients.

Introduction: Information derived from animal models and neuroradiological studies in humans indicates that males and females exhibit differences in the functional and anatomical organisation of the brain. This study aimed to evaluate the effect of gender in ictal behaviour considering lateralisation in a group with homogeneous pathology., Methods: Patients with hippocampal seizures who underwent temporal lobectomy and who were seizure-free during one year of follow-up were selected. Surgery was performed on the right side in 27 patients and on the left side in 21. Videotape recordings of the patients were reviewed in order to investigate ictal behaviour. There were 42 seizure episodes in 20 males and 40 in 21 females. For auras, 48 patients' data were reviewed. Ictal behaviour was evaluated taking into consideration the lateralisation of seizures and gender differences., Results: Ictal vocalisation was significantly higher in females with right temporal lobe epilepsy (RTLE) (P < 0.05). Forced head deviation was significantly higher in males with left temporal lobe epilepsy (LTLE) (P < 0.03) and in females with RTLE (P < 0.0001). Unforced head deviation was significantly higher in males with RTLE (P < 0.002). Ipsilateral eye deviation was significantly higher in RTLE, with no differences between males and females. Postictal coughing was significantly higher in RTLE, again with no differences between males and females (P < 0.03). With regard to automatisms, posturing and nose wiping, there was no difference between right and left temporal lobe seizures or between genders., Conclusions: To the best of our knowledge, this study is the first demonstrating differences in ictal behaviour between females and males, thus showing that gender is related to different functional and anatomical organisations of the human brain., (Copyright 2003 BEA Trading Ltd.)

Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to have a safer profile and additional anti-inflammatory and immuno-modulatory properties compared to parent compounds. Preventive treatment of experimental autoimmune encephalomyelitis (EAE)-induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55-with the NO-releasing derivative of flurbiprofen HCT1026 delayed disease onset and significantly decreased disease severity. HCT1026 treatment was associated to (i) decreased mRNA levels of pro-inflammatory cytokines, caspase-1, and iNOS in blood cells; (ii) decreased ability of encephalitogenic T cells to proliferate; (iii) reduced number of central nervous system (CNS)-infiltrating T cells; (iv) decreased axonal loss and demyelination; (v) increased CD4(+) CD69(-) CD25(+) regulatory T cells in the spleen.

There is emerging evidence that matrix metalloproteinases (MMPs) might be involved in blood brain barrier (BBB) breakdown in multiple sclerosis. A group of natural tissue inhibitors of metalloproteinases (TIMPS) regulates proteolytic activity to prevent tissue damage. TIMP-1 and MMP-9 are known to be secreted as heterodimers and TIMP-1 preferentially functions to inhibit MMP-9 activity. In this present study, the effects of IFNbeta-1a on serum MMP-9 and TIMP-1 were evaluated longitudinally during a one-year period. The MMP-9 levels showed no significant changes while TIMP-1 levels gradually and significantly increased during 3rd and 6th months of therapy compared with pretreatment levels.

Nitric oxide was studied to investigate its possible involvement in the promotion of breast carcinoma: both the development of the primary tumour and the process of metastasis seem to be influenced by the presence and the amount of nitric oxide. We review the available literature on this topic, which seems to suggest an influence of nitric oxide on the cancer cell biology in breast carcinoma, but the argument is still controversial. More studies are needed to clarify the sequence of events and the real impact of nitric oxide on the behaviour of the disease.

Paraneoplastic syndromes are the rarest neurological complications in patients with cancer. The neurological paraneoplastic syndromes that are mainly associated with breast cancer are subacute cerebellar degeneration, paraneoplastic retinopathy, opsoclonus-myoclonus syndrome, lower motor neuron diseases and Stiff-man syndrome. The aim of this paper is to briefly outline these paraneoplastic neurological syndromes and consider their relation to breast carcinoma.