Erkingül Shugaiv

Long‐term MRI findings in neuromyelitis optica: seropositive versus seronegative patients

Neuromyelitis optica (NMO) is a severe demyelinating inflammatory disorder associated with serum antibodies against aquaporin 4 (AQP4‐Ab). A significant number of patients with NMO remain seronegative over time. Long‐term observational magnetic resonance imaging (MRI) studies of the CNS in patients with NMO are rare or of limited duration. The objective of this study is to determine long‐term MRI characteristics of seropositive and seronegative patients, and assess possible overlap with multiple sclerosis (MS).

Effect of short-term interferon-β treatment on cytokines in multiple sclerosis: Significant modulation of IL-17 and IL-23

Therapeutic effect of interferon-β (IFN-β) treatment has been associated with modulation of the balance between Th1, Th17, Th2 and regulatory T (Treg) cells, whereas the impact of disease modifying drugs on Th9-immunity in multiple sclerosis (MS) has not been studied. To investigate the short-term effects of IFN-β treatment on cytokines in MS, we determined serum levels of IL-17, IL-23, IL-10, IL-4, IFN-γ, IL-9 and TGF-β in relapsing remitting MS patients before and 2 months after IFN-β treatment by ELISA. MS patients showed increased IL-17, IL-23 and IL-4 levels and decreased IL-9 levels as compared to healthy controls. IFN-β treatment only reduced IL-17 and IL-23 levels, whereas the levels of other cytokines remained unchanged. IFN-β treatment appears to exert its earliest therapeutic effect on Th17-immunity. The influence of IL-9 on MS pathogenesis needs to be further studied.

Glycine receptor and myelin oligodendrocyte glycoprotein antibodies in Turkish patients with neuromyelitis optica.

BACKGROUND Seronegative NMO is highly prevalent in non-Western countries implying the presence of as yet unknown antibodies (Ab). We investigated potential novel Ab in aquaporin-4 Ab (AQP-4-Ab) positive and negative NMO patients. METHODS Sera of 20 NMO patients were examined for AQP-4, myelin oligodendrocyte glycoprotein (MOG) and glycine receptor (GlyR) Ab by cell-based assays. RESULTS AQP-4-Ab was identified in 10 NMO patients, MOG-Ab was detected only in one AQP-4-Ab positive patient and GlyR-Ab was detected in two AQP-4-Ab negative patients. GlyR-Ab positive patients displayed simultaneous optic neuritis and transverse myelitis attacks and relatively low disability, whereas MOG and AQP-4-Ab double positive patient had a significantly increased disability. CONCLUSION This study showed for the first time the presence of GlyR-Ab in Turkish NMO patients. In contrast with previous reports, MOG Ab does not appear to be a distinctive marker for Turkish AQP-4-Ab negative NMO patients.

Uveitis as a prognostic factor in multiple sclerosis

Uveitis is occasionally encountered in multiple sclerosis (MS) patients. The objective of this report is to investigate whether uveitis has a prognostic impact on the clinical course of MS. Several clinical and demographic features were compared between 41 MS patients with uveitis and 100 randomly selected MS patients without uveitis. While there were no significant differences by means of gender, age of MS onset, oligoclonal band positivity and disease duration, EDSS and progression index (PI) scores of MS patients with uveitis were significantly lower than those without uveitis (p = 0.004 and <0.001, respectively). Our results suggest that uveitis might be used as a good prognostic factor.

Impact of cigarette smoking on conversion from clinically isolated syndrome to clinically definite multiple sclerosis.

Multiple sclerosis (MS) is known to be influenced by various environmental factors including cigarette smoking. To identify the impact of smoking on conversion from clinically isolated syndrome (CIS) to clinically definite MS (CDMS), 95 consecutive uniformly treated smoker (n = 31) and nonsmoker (n = 64) CIS patients were evaluated retrospectively. The smoker CIS patients did not differ from nonsmokers by means of demographic and clinical findings. In addition, there was no difference between the two groups with respect to rate and time of conversion to CDMS. However, white matter lesions were detected in magnetic resonance imagings (MRIs) of all smoking versus 54 of 64 (63.5%) nonsmoking CIS patients (p = 0.02). Our results show that smoking does not predict conversion from CIS to CDMS. However, smoking may be associated with the appearance of white matter lesions on MRI at CIS onset.

Progressive encephalomyelitis with rigidity and myoclonus: a syndrome with diverse clinical features and antibody responses.

Background/Aims: To better characterize progressive encephalomyelitis with rigidity and myoclonus (PERM) syndrome and identify novel PERM phenotypes. Methods: The clinical features and antibody status of PERM patients were investigated using immunoblots, cell-based assays, RIA, protein macroarray and ELISA. Results: Two patients with supratentorial involvement showed abnormal PET or EEG findings. One patient was discovered to have renal cell carcinoma, and protein macroarray revealed Ma3-antibodies. Another patient with leucine-rich, glioma-inactivated 1 (LGI1) and glutamic acid decarboxylase (GAD) antibodies showed a good response to immunotherapy. Conclusion: The heterogeneity of the immunological features suggests that PERM is caused by diverse pathogenic mechanisms. Seropositivity to well-characterized neuronal cell surface antigens might indicate a good treatment response.

Aquaporin-1 Antibody in Neuromyelitis Optica Patients

Background/Methods: To find out the prevalence of aquaporin-antibody (Aqp-Ab) and characterize Aqp-Ab associated clinical features in NMO, Aqp-1 and Aqp-4-Abs were examined using radioimmunoprecipitation and cell-based assays, respectively. Results: Aqp-4 and Aqp-1-Abs were detected in 20/30 and 8/30 NMO patients, respectively. One patient was Aqp-1-Ab single-positive, 13 patients were Aqp-4-Ab single-positive, 7 patients were Aqp-4/Aqp-1-Ab double-positive and 9 patients were seronegative. All double-positive patients had optic neuritis during the first attack. Only 2/29 MS patients and none of the control idiopathic intracranial hypertension patients were Aqp-1-Ab positive. Conclusion: Aqp-1-Ab is usually detected in Aqp-4-Ab positive NMO patients and might be involved in optic neuritis pathogenesis.

Predictive value of early serum cytokine changes on long-term interferon beta-1a efficacy in multiple sclerosis

Background: In a previous study, we had evaluated short-term effects of interferon beta-1a (IFNB-1a) 44 μg s.c. three times per week treatment on serum levels of IFN-gamma (IFNG), IL-23, IL-17, IL-10, IL-9, IL-4 and TGF-beta (TGFB) and found a reduction only in IL-17 and IL-23 levels after 2 months of treatment. Methods: Using the same multiple sclerosis (MS) cohort, we assessed the predictive value of early cytokine level changes (difference between 2nd month and baseline levels as measured by ELISA) on the efficacy of long-term IFNB-1a treatment. Results: The alteration in IFNG levels of patients without any relapse was statistically lower than that of patients having one or more relapses (p = 0.019, Students t-test). When patients with or without expanded disability severity scale (EDSS) progression were compared, none of the cytokine level changes showed a significant difference between groups. IL-17 and IL-23 level changes did not predict relapse and EDSS progression in IFNB-1a-treated MS patients. Conclusion: Our results show that the predictive power of early IFNG measurement on relapse occurrence may potentially extend a time span of several years.

Association of Demyelinating and Inflammatory Bowel Diseases: A Case Series and Overview of the Literature

Neurological complications of inflammatory bowel diseases (i.e., ulcerative colitis and Crohns disease) can be summarized as a combination of neuromuscular manifestations, cerebrovascular and demyelinating diseases that can be seen in approximately 3% of patients. In addition, asymptomatic cerebral white matter lesions may be detected in these patients. Clustering of diseases within families may be explained by the exposure to similar environmental factors, shared genes, or complex interactions between genetic and environmental factors. Here we report an epileptic patient with Crohns disease and cerebral white matter lesions, a family with ulcerative colitis and multiple sclerosis and two patients who have both multiple sclerosis and Crohns disease.

Reduced serum orexin-A levels in autoimmune encephalitis and neuromyelitis optica patients

Sleep-related structures in the brain appear to be frequently affected in antibody-mediated autoimmunedisorders of the central nervous system (CNS), such as autoimmune encephalitis and neuromyelitis optica (NMO), resulting in sleep disorders generally occurring in the form of excessive daytime sleepiness (EDS), narcolepsy, insomnia or rapid eye movement sleep behavior disorder (RBD) [1–5]. Orexin is a neurotransmitter that regulates arousal, wakefulness and appetite and is produced by a small population of hypothalamic cells. Deficient orexin production is mostly detected in narcolepsy patients [6]. Likewise, sleep problems of antibody-mediated CNS disorders have often been associated with reduced cerebrospinal fluid (CSF) orexin levels [1–4]. Sleep disorders in autoimmune encephalitis have been mostly associated with Ma2, N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma inactivated 1 (LGI1)-antibodies [1–5,7]. Our current knowledge on sleep disorders in antibody-mediated CNS diseases is mostly limited to case reports [1,2,7] and a systemic screening of sleep-related clinical and laboratory findings is not available. To find out the frequency of symptoms suggestive of sleep disorders and reduced serum orexin levels in antibody-mediated autoimmune disorders of the CNS, medical charts of 36 patients with limbic encephalitis, encephalomyelitis or brainstem encephalitis (17 women; age range, 21–69 years) and 20 NMO patients with or without aquaporin4 (Aqp-4) antibody (16 women; age range, 18–53 years) admitted to our outpatient clinic were retrospectively reviewed (Table 1). Any sleep-related complaints recorded in the medical charts were noted down. Additionally, symptoms suggestive of RBD (acting out violent dreams, vocalization and episodes of kicking, biting and screaming during sleep) were also recorded. Orexin-A levels of the patients were measured in the archived sera obtained in the presence of active neurological symptoms. To avoid inclusion of non-autoimmune cases, only patients with well-characterized anti-neuronal antibodies (Hu, Ma2, Ri, NMDAR and LGI1) were recruited. All NMO patients met Wingerchuks revised diagnostic criteria [8]. Magnetic resonance imaging (MRI) examinations were performed on various scanners with a minimum field strength of 1.5 Tesla. Slice thickness of scans ranged from 3 mm to 5 mm. All patients received gadolinium. Brain and spinal