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INTRODUCTION: Sleep disturbances are being increasingly recognized in association with autoimmune encephalitis (AIE). We investigated the prevalence of sleep-related symptoms and polysomnographic features of patients with AIE and the long-term outcomes in these patients in a multi-center, prospective study from Turkey. METHODS: We prospectively evaluated patients with definite AIE in a common database including demographics, AIE-related and sleep-related symptomatology. Maximum and latest modified Rankin scores (mRS) and Liverpool Outcome Score (LOS) were noted. RESULTS: Of 142 patients, 87 patients (61.3%) fulfilled the criteria for definite AIE (mean age, 46.8+18.8 years; 51.7% women; mean disease duration, 21.0+38.4 months). 78.9% of patients had at least one or more new onset or worsened sleep-related symptomatology: insomnia (55.3%), excessive daytime sleepiness (EDS, 28.0%), sleep apnea (18.7%), REM sleep behavior disorder (RBD, 17.3%), restless legs syndrome (10.7%) and oneiric stupor (9.3%). Sleep efficiency, N3 and REM sleep were decreased and N1 sleep was increased in patients with Ab[+] AIE. LOS points were highest in those with insomnia and sleep apnea, and lowest in those with EDS, RBD and oneiric stupor. RBD and sleep apnea were more common in anti-LG1 Ab[+] group than anti-NMDAR Ab[+] group. Index of periodic leg movements was highest in anti-LG1 Ab[+] group. Patients with EDS and oneiric stupor had more common memory problems. Maximum and latest mRS scores were positively correlated with EDS and oneiric stupor. EDS, RBD and oneiric stupor were negatively correlated with LOS points. CONCLUSION: Our study emphasizes the presence and importance of early diagnosis of sleep disturbances in AIE in regard to their deteriorative influences on disease prognosis.
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OBJECTIVES: Transcranial direct current stimulation (tDCS) has been suggested as an alternative treatment option for migraine. The present study aimed to evaluate the efficacy of tDCS on clinical outcomes in addition to calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide 38 (PACAP-38) levels in individuals with menstrual-related migraine (MRM) for the first time. MATERIALS AND METHODS: In this parallel study, 58 female patients between the ages of 18 and 45 years, including 36 with MRM and 22 with nonmenstrual migraines (nMM), were recruited. Sessions of 2-mA 20-minute anodal tDCS were administered over the left dorsolateral prefrontal cortex within three consecutive days (1:1 active and sham stimulation). Migraine attack frequency, severity, analgesic usage, CGRP, and PACAP-38 levels of the patients were evaluated before and one month after tDCS. RESULTS: After tDCS, in the active group compared with the sham group, the frequency (p = 0.031), the severity of attacks (p = 0.003), the number of days with headache (p = 0.004), and the analgesic usage (p = 0.024) were all decreased. In both MRM and nMM groups, the frequency and severity of attacks and analgesic usage were decreased in those receiving active stimulation (p < 0.001 for each). CGRP and PACAP-38 levels were no different in the active group and the sham group after tDCS. CONCLUSIONS: tDCS was shown to be efficacious in migraine prophylaxis and a valuable option for migraine and MRM treatment. The absence of changes in serum CGRP and PACAP-38 levels suggests that tDCS efficacy may stem from distinct cerebral electrophysiological mechanisms.
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Péptido Relacionado con Gen de Calcitonina , Trastornos Migrañosos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Estimulación Transcraneal de Corriente Directa , Humanos , Femenino , Adulto , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/sangre , Trastornos Migrañosos/terapia , Trastornos Migrañosos/sangre , Péptido Relacionado con Gen de Calcitonina/sangre , Adulto Joven , Estimulación Transcraneal de Corriente Directa/métodos , Resultado del Tratamiento , Persona de Mediana Edad , AdolescenteRESUMEN
OBJECTIVES: Recent studies have shown that the distribution of the tryptophan/kynurenine pathway (KP) plays a role in the development of obsessive-compulsive disorder (OCD). We aimed to reveal the relationship between CYP1A1 rs464903 and aryl hydrocarbon receptor (AhR) rs10249788 associated with the KP and interferon gamma (IFN γ) and oxidative stress in OCD. METHODS: In our study, the serum and DNAs of 150 samples, including 100 OCD patients and 50 controls, were used. The activity of glutathione peroxidase (GSH-Px), and the levels of IFN γ, thiobarbituric acid reactive substances (TBARS), tryptophan, and kynurenine were determined by biochemical methods. AhR rs10249788 and cytochrome P450 family CYP1A1 rs4646903, which interact directly with the KP, were analysed by polymerase chain reaction followed by restriction fragment length polymorphism. P < 0.05 was considered statistically significant. RESULT: There were no significant differences between groups in CYP1A1 rs4646903 and AhR rs10249788 while tryptophan and IFN γ were found to be higher in controls (p < 0.001, for both), and TBARS and indolamine-2,3-dioxygenase were found to be higher in OCD (p < 0.001, for both). There were significant correlations between IFN γ and TBARS and GSH-Px (p = 0.028, p = 0.020, respectively) in the OCD group. CONCLUSIONS: For the first time studied in OCD, it has been shown that IFN γ, tryptophan, oxidative stress parameters, and gene variants of CYP1A1 rs4646903 anAhR rs10249788 are shown effective on the KP.
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Background and purpose:
Although serum anti-neuronal antibodies are found in acute ischemic stroke (AIS) patients, it is not completely clear whether they are already present before the cerebrovascular event or emerge thereafter.
. Methods:Sera of 21 consecutive first-ever AIS patients were collected within the first day of AIS (baseline), as well as 1 and 6 months after AIS. Well-characterized and novel anti-neuronal antibodies were investigated by cell-based assays, immunoblotting and indirect immunohistochemistry.
. Results:None of the AIS sera collected at different time points showed well-characterized antibodies. In 7 patients, 1- and 6-month sera (but not baseline sera) showed IgG mostly reacting with soma and dendrites of cerebellar Purkinje cells. Antibody-positive patients did not differ in terms of clinical and etiological features.
. Conclusion:Our results provide evidence for the antibody-triggering action of AIS. Although anti-cerebellar antibodies are not associated with the severity of stroke, they may potentially contribute to chronic post-stroke complications and disability.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular/complicaciones , Cerebelo , Isquemia Encefálica/complicacionesRESUMEN
BACKGROUND: The involvement of inflammation in the pathophysiology of cluster headache (CH) has been suggested, with a role implied for interleukin (IL)-1ß. We aimed to measure peripheral blood expression levels of IL-1ß-inducing systems, the inflammasome complex, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and investigate their values as putative biomarkers in CH. METHODS: In this cross-sectional study conducted in the Headache Unit of Istanbul University, Turkey, blood mononuclear cells (PBMCs) and sera were collected from 30 patients with episodic migraine, 4 with chronic CH, and 47 healthy individuals. Levels of inflammasome complex components (NLRP1, NLRP3, caspase 1, and ASC), end products of inflammasome complex activity (IL-1ß, IL-18, and nitric oxide synthase isoforms), neuron-specific enolase, other inflammatory factors (NF-κB, HMGB1, and s100b), and anti-inflammatory IL-4 were measured by real-time quantitative polymerase chain reaction and/or enzyme-linked immunosorbent assay. RESULTS: NLRP3 expression levels were significantly reduced in PBMC samples of patients with CH, obtained during CH attacks (n = 24) or headache-free (out of cycle) episodes (n = 10). CH-attack patients showed greater expression levels of IL-1ß (2-ΔΔCT median [25th-75th percentile], 0.96 [0.66-1.29 vs. 0.52 [0.43-0.73]) and NF-κB (1.06 [0.66-3.00] vs. 0.62 [0.43-1.19]) in PBMCs but not in sera compared with headache-free CH patients. However, these differences did not attain statistical significance (p = 0.058 and p = 0.072, respectively). Moreover, NLRP1 (52.52 [35.48-67.91] vs. 78.66 [54.92-213.25]; p = 0.017), HMGB1 (11.51 [5.20-15.50] vs. 13.33 [8.08-18.13]; p = 0.038), S100b (569.90 [524.10-783.80] vs. 763.40 [590.15-2713.00]; p = 0.013), NSE (11.15 [6.26-14.91] vs. 13.93 [10.82-19.04]; p = 0.021), nNOS (4.24 [3.34-12.85] vs. 12.82 [4.52-15.44]; p = 0.028), and eNOS (64.83 [54.59-91.14] vs. 89.42 [61.19-228.40]; p = 0.034) levels were lower in patients with three or more autonomic manifestations (n = 9). No correlation was found between inflammation factors and clinical parameters of CH. CONCLUSION: Our results support the involvement of the IL-1ß system in attacks of CH. However, the components of the inflammasome complex are suppressed in the peripheral blood and do not appear to play a role in the pathophysiology of CH. These findings argue against a potential biomarker value of the inflammasome complex in CH.
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Cefalalgia Histamínica , Proteína HMGB1 , Cefalalgia Histamínica/metabolismo , Estudios Transversales , Proteína HMGB1/metabolismo , Humanos , Inflamasomas/metabolismo , Inflamación , Interleucina-1beta , Leucocitos Mononucleares/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismoRESUMEN
OBJECTIVE: Narcolepsy is a chronic sleep disorder long hypothesised to be an autoimmune disease. Complement-mediated immune mechanisms have not been investigated in detail in narcolepsy. Our aim was to establish the significance of classical pathway activation in narcolepsy. METHODS: Sera of 42 narcolepsy patients and 26 healthy controls were screened with ELISA to determine the levels of C1q, C3a, C4d and complement component 4 binding protein (C4BP). A home-made ELISA method was developed to detect antibodies to C4BP-alpha (anti-C4BPA). The correlation between complement levels and clinical findings was examined. RESULTS: C1q levels were significantly higher in narcolepsy patients while C4d and C4BP levels were significantly lower compared to healthy controls. C3a levels were comparable among patients and controls. Eleven narcolepsy patients showed serum anti-C4BPA levels. Total rapid eye movements (REM) time, sleep onset latency, REM sleep latency, sleep activity, percentage of wakefulness after sleep onset and Epworth sleepiness scale scores were correlated with levels of different complement factors. CONCLUSION: Complement-mediated immune mechanisms might partake in narcolepsy pathogenesis. The precise role of autoantibodies on complement level alterations needs to be investigated. Levels of complement factors and degradation products may potentially be utilised as biomarkers to predict the clinical severity of narcolepsy.
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Vía Clásica del Complemento , Narcolepsia , Complemento C1q , Humanos , Narcolepsia/diagnóstico , Sueño REM/fisiología , Vigilia/fisiologíaRESUMEN
BACKGROUND: Clinical exacerbations characterized with neurological symptoms are observed in around 10% of Behçet's disease (BD) patients and may culminate in severe disability. Although certain immunological factors have been associated with disease activity in neuro-Behçet's disease (NBD), biomarkers for monitoring the clinical outcome of NBD have not been properly investigated. METHODS: Levels of neurofilament light chain (NFL), homeobox protein Hox-B3 (HoxB3), and YKL-40 were measured in cerebrospinal fluid (CSF) samples of 23 parenchymal (n = 16) and nonparenchymal (n = 7) NBD patients obtained during NBD attacks by ELISA. Parameters of clinical progression and outcome were assessed for an average follow-up period of 3.9 ± 1.3 years. RESULTS: Parenchymal NBD patients showed elevated CSF levels of NFL, HoxB3, and YKL-40 as compared to nonparenchymal patients. NBD patients showing an increase in modified Rankin score (mRS) values during follow-up had significantly higher CSF NFL levels. Patients with relatively lower CSF NFL levels (<1000 ng/L) did not develop attacks or cognitive impairment interfering with daily life activities during follow-up. NFL levels correlated with disease duration and mRS at the last follow-up visit, while HoxB3 levels correlated with a number of attacks during follow-up. DISCUSSION: CSF level of NFL appears to predict the prospective somatic and cognitive disability in NBD patients and may thus be potentially used as a biomarker of clinical outcome in this disease.
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Síndrome de Behçet , Humanos , Síndrome de Behçet/diagnóstico , Biomarcadores , Proteína 1 Similar a Quitinasa-3 , Filamentos Intermedios , Estudios ProspectivosRESUMEN
AIM: Idiopathic intracranial hypertension (IIH), a disease of obscure origin, is characterized by headache and visual disturbances due to increased intracranial pressure. Recent line of evidence has suggested involvement of inflammation in IIH pathogenesis thus bringing forward anti-glial autoimmunity as a potential contributor of IIH. Glial fibrillary acidic protein (GFAP) is a major astrocytic autoantigen associated with a specific form of meningoencephalitis. MATERIALS AND METHODS: In this study, we investigated the presence of GFAP-antibody in 65 sera (49 obtained during active disease and 16 during remission) and in 15 cerebrospinal fluid (CSF) samples of 58 consecutively recruited IIH patients using cell based assay and indirect immunohistochemistry. RESULTS: GFAP-antibody was found in active period sera of 2 IIH patients with classical symptoms and good treatment response. Two remission period sera obtained at different time points from one of these cases showed lower titers of GFAP-antibody positivity. IgG from positive samples yielded an astrocytic immunoreactivity pattern. None of the CSF samples showed GFAP-antibodies. CONCLUSIONS: These results suggest that anti-astrocyte autoimmunity might be present in a fraction of IIH patients. Exact pathogenic significance of this association needs to be further studied.
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Proteína Ácida Fibrilar de la Glía/sangre , Proteína Ácida Fibrilar de la Glía/inmunología , Seudotumor Cerebral/sangre , Seudotumor Cerebral/inmunología , Adulto , Autoanticuerpos/sangre , Femenino , Humanos , Masculino , Seudotumor Cerebral/líquido cefalorraquídeoRESUMEN
Objectives: Vestibular migraine (VM) is an under-recognized entity with substantial burden for the individual and society. The underlying mechanism of VM and its distinction from other migraine mechanisms still remain unclear. Inflammatory pathways have been suggested to contribute to vestibular migraine. Our aim was to further investigate the possible role of inflammation in the pathophysiology of VM.Methods: We recruited 30 patients with VM diagnosed according to ICHD-3 criteria and 50 gender- and age-matched controls. Blood samples were obtained from 11 VM patients during an attack and from 13 VM patients under prophylactic treatment. Plasma levels of calcitonin gene related peptide (CGRP), neurokinin A (NKA), substance P (SP), NLRP1, NLRP3, caspase-1, IL-1ß, IL-6, TNF-α and NFκB were measured by ELISA.Results: IL-6 levels were significantly reduced in VM patients, whereas levels of other inflammation parameters were comparable to those of healthy controls. Levels of inflammatory mediators were not correlated with clinical parameters. Likewise, there were no significant differences among VM patients with and without headache attack and prophylactic treatment.Conclusion: Our results argue against involvement of systemic inflammation in the pathophysiology of VM.
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Mediadores de Inflamación/sangre , Trastornos Migrañosos/sangre , Vértigo/sangre , Adulto , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/complicaciones , Vértigo/complicaciones , Vestíbulo del Laberinto/fisiopatologíaRESUMEN
Background Although specific role players are currently unknown, contribution of inflammatory mediators has been suggested in the pathophysiology of idiopathic intracranial hypertension (IIH), which is a disease more prevalent in obese female individuals of childbearing age. We aimed to investigate the levels of adipokines and cytokines to demonstrate possible markers for inflammation that participate in IIH pathophysiology and their association with clinical features of IIH. Methods IIH patients, diagnosed according to the revised criteria, and age-, gender- and body mass index (BMI)-matched healthy controls were enrolled in this study. Serum samples were evaluated for insulin-like growth factor 1, insulin, nesfatin, adiponectin, interleukin (IL)-1ß, IL-6, IL-8, leptin, plasminogen activator inhibitor type-1, resistin, tumour necrosis factor-alpha (TNF-α) and monocyte chemotactic protein 1 via enzyme-linked immunosorbent assay or multiplex immunoassays. Results IL-1ß level was significantly higher ( p = 0.012), and IL-8 and TNF-α levels were significantly lower in the IIH group ( p < 0.001 and p = 0.008, respectively) compared to the control group. There were no correlations between the cytokine/adipokine levels and age, BMI, disease duration, and cerebrospinal fluid oligoclonal bands. There were also no significant differences in cytokine and adipokine levels between IIH patients regarding visual impairment. However, statistically significant differences were found between IIH patients with relapse versus healthy controls regarding IL-1ß ( p = 0.007), IL-8 ( p = 0.001) and TNF-α ( p = 0.017) levels. Other investigated cytokines and adipokines showed no significant alterations in IIH patients investigated in the remission period. Conclusion Altered serum levels of IL-1ß, IL-8 and TNF-α seem to be associated with IIH pathogenesis, and these cytokines may be used as prognostic markers in IIH to predict relapse.
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Adipoquinas/sangre , Mediadores de Inflamación/sangre , Seudotumor Cerebral/sangre , Seudotumor Cerebral/diagnóstico por imagen , Adulto , Biomarcadores/sangre , Femenino , Humanos , Angiografía por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been recently identified in neuro-Behcet's disease (NBD) patients. To delineate the potential pathogenic action of these antibodies, pooled sera from seven NBD patients with neuropil antibodies and seven healthy controls were divided into purified IgG and IgG-depleted serum (IgG-DS) fractions and each fraction was administered into lateral ventricles of rats. NBD IgG-injected rats showed reduced locomotor activity in the open field test as compared to NBD IgG-DS, healthy control IgG, healthy control IgG-DS and PBS injected rats (n = 10 for each group). There were no significant differences among treatment groups by means of anxiety-like behaviors (assessed by elevated plus maze test) and learning/memory functions (assessed by passive avoidance test). Administration of NBD IgG on cultured SH-SY5Y neuroblastoma cells induced significantly increased cell death and apoptosis (as measured by nucleosome levels in the supernatants) as compared to other treatment groups. Our results suggest that IgGs isolated from sera of neuropil antibody-positive NBD patients have a neurotoxic action, which is presumably mediated by apoptotic mechanisms. Motor deficits frequently observed in NBD patients might at least partially be caused by the pathogenic action of anti-neuronal IgG.
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Síndrome de Behçet/inmunología , Inmunoglobulina G/farmacología , Proteínas Asociadas a Microtúbulos/inmunología , Neurópilo/inmunología , Adulto , Animales , Animales Recién Nacidos , Ansiedad/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunoglobulina G/sangre , Locomoción/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Persona de Mediana Edad , Neuroblastoma/patología , Nucleosomas/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
BACKGROUND: Obsessive-compulsive disorder (OCD) is a mental disease characterized by recurrent and intrusive thoughts and repetitive behaviours that negatively affect the quality-of-life of the patients. Recent studies have implicated the participation of neuronal nitric oxide in OCD pathogenesis as a neurotransmitter modulator. AIMS: To identify whether variations in neuronal nitric oxide synthase (nNOS) genes may render individuals susceptible to OCD development. METHODS: This study examined nNOS polymorphisms in 100 OCD patients and 121 unrelated healthy controls by polymerase chain reaction and restriction enzyme digestion methods. RESULTS: nNOS 276 C + genotype incidence was significantly higher in OCD patients than controls and conferred a 2-fold increased risk for OCD. No significant differences were observed in frequencies of nNOS 84 genotypes between patients and controls. CONCLUSION: This study shows an association between nNOS gene polymorphism and OCD. Exact mechanisms by which nNOS gene variants contribute to OCD pathogenesis need to be further investigated.
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Óxido Nítrico Sintasa de Tipo I/genética , Trastorno Obsesivo Compulsivo/genética , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
OBJECTIVE: Our aim was to investigate the prevalence of neuronal autoantibodies (NAbs) in a large consecutive series with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to elucidate the clinical and laboratory clues for detection of NAbs in this prototype of frequent, drug-resistant epilepsy syndrome. METHODS: Consecutive patients diagnosed with MTLE fulfilling the MRI criteria for HS were enrolled. The sera of patients and various control groups (80 subjects) were tested for eight NAbs after ethical approval and signed consents. Brain tissues obtained from surgical specimens were also investigated by immunohistochemical analysis for the presence of inflammatory infiltrates. The features of seropositive versus seronegative groups were compared and binary logistic regression analysis was performed to explore the differentiating variables. RESULTS: We found antibodies against antigens, contactin-associated protein-like 2 in 11 patients, uncharacterised voltage-gated potassium channel (VGKC)-complex antigens in four patients, glycine receptor (GLY-R) in 5 patients, N-methyl-d-aspartate receptor in 4 patients and γ-aminobutyric acid receptor A in 1 patient of 111 patients with MTLE-HS and none of the control subjects. The history of status epilepticus, diagnosis of psychosis and positron emission tomography or single-photon emission CT findings in temporal plus extratemporal regions were found significantly more frequently in the seropositive group. Binary logistic regression analysis disclosed that status epilepticus, psychosis and cognitive dysfunction were statistically significant variables to differentiate between the VGKC-complex subgroup versus seronegative group. CONCLUSIONS: This first systematic screening study of various NAbs showed 22.5% seropositivity belonging mostly to VGKC-complex antibodies in a large consecutive series of patients with MTLE-HS. Our results indicated a VGKC-complex autoimmunity-related subgroup in the syndrome of MTLE-HS.
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Autoanticuerpos/sangre , Epilepsia Refractaria/inmunología , Epilepsia del Lóbulo Temporal/inmunología , Hipocampo/inmunología , Neuronas/inmunología , Canales de Potasio con Entrada de Voltaje/inmunología , Adulto , Trastornos del Conocimiento/inmunología , Trastornos del Conocimiento/patología , Estudios Transversales , Epilepsia Refractaria/patología , Epilepsia del Lóbulo Temporal/patología , Femenino , Estudios de Seguimiento , Hipocampo/patología , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuronas/patología , Trastornos Psicóticos/inmunología , Trastornos Psicóticos/patología , Valores de Referencia , Esclerosis/inmunología , Esclerosis/patología , Estado Epiléptico/inmunología , Estado Epiléptico/patologíaRESUMEN
Background Chemokines are known to play a major role in driving inflammation and immune responses in several neuroinflammatory diseases, including multiple sclerosis, Alzheimer's disease and Parkinson's disease. Inflammation has also been implicated in the pathogenesis of schizophrenia. Aim We aimed to investigate a potential link between chemokines and schizophrenia and analyze the role of MCP-1-A2518G, SDF-1-3'A, CCR5-delta32, CCR5-A55029G, CXCR4-C138T and CCR2-V64I gene polymorphisms in the Turkish population. Methods Genotyping was conducted by PCR-RFLP based on 140 patients and 123 unrelated healthy controls to show the relation between chemokine gene variants and schizophrenia risk. Results Frequencies of CCR5-A55029G A genotypes and CCR5-A55029G AG genotypes were found higher in patients than the controls and even also CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes significantly associated according to Bonferroni correction. However, no significant association was found for any of the other polymorphisms with the risk of schizophrenia. Conclusions Our findings suggest that CCR5-A55029G polymorphisms and CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes might have association with schizophrenia pathogenesis.
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Quimiocinas/genética , Variación Genética/genética , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Receptores CCR2/genética , Receptores CCR5/genética , Esquizofrenia/epidemiología , Turquía/epidemiologíaRESUMEN
BACKGROUND: Bipolar disorder-I (BD-I) is a complex illness, and multiple genes and environmental factors determine its pathogenesis. Several studies have ascertained that BD-I and inflammation are linked through shared genetic polymorphisms and gene expression, as well as altered cytokine levels. COX-2 gene polymorphisms affecting COX-2 levels may be associated with BD-I by altering the inflammatory response. SUBJECTS AND METHODS: We investigated COX-2-765GâC and COX-2-1195AâG gene polymorphisms, which might be related for BD-I. The present analyses are based on 180 subjects with bipolar I disorder-I and 170 non-bipolar subjects. Genotyping of COX-2 gene polymorphisms (COX-2-765GâC, COX-2-1195AâG) were detected by PCR-RFLP. RESULTS: We found a positive association of COX-2 gene variants for development of BD-I. There were statistically significant differences in COX-2-1195AâG genotypes and alleles between the controls and patients (p:0.000; p:0.000). The indivuals with COX-2-1195AâG AA genotype had seems to be associated for BD-I (p:0.000). CONCLUSIONS: It seems that there is a protective role of COX-2-1195AâG G+ genotype against BD-I (p:0.000). In addition, there was a weak linkage disequilibrium between COX-2-765GâC and COX-2-1195AâG polymorphisms. Our findings suggest that COX-2-1195AâG AA genotype may faciliate the development of BD-I.
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Trastorno Bipolar/genética , Ciclooxigenasa 2/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adulto , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Introduction: Although the contribution of enhanced glial activity in seizure induction is increasingly recognized, the role of glia-induced neuroinflammation in the physiopathology of epileptic encephalopathy (EE) has been scarcely investigated. Methods: To delineate the contribution of glial activity in EE, we measured levels of glia-derived mediators with previously described biomarker value, including glial fibrillary acidic protein (GFAP), high mobility group box 1 (HMGB1), chitinase-3-like protein 1 (CHI3L1), soluble CD163 (sCD163) and triggering receptor expressed on myeloid cells 2 (TREM2) by ELISA in sera of patients with idiopathic West syndrome (WS, n=18), idiopathic Lennox-Gastaut syndrome (LGS, n=13) and healthy controls (n=31). Results: Patients with EE showed significantly higher CHI3L1 levels compared to healthy controls. Levels of HMGB1, CHI3L1, sCD163 and TREM2 were higher in LGS patients than WS patients and/or healthy controls. One or more of the investigated mediators were associated with treatment responsiveness, disease severity and presence of pathological features on electroencephalography (EEG). Conclusions: To our knowledge, our findings provide the initial patient-based evidence that astrocyte- and microglia-mediated neuroinflammation might be involved in the pathogenesis of LGS and WS. Moreover, glial mediators may serve as prognostic biomarkers in patients with idiopathic EE.
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Introduction: Parenchymal Neuro-Behçet's disease (p-NBD) usually presents with a characteristic lesion in the mesodiencephalic region. However, there is a lack of information regarding the axonal integrity of normal-appearing white matter in p-NBD. Diffusion tensor imaging (DTI) is based on the properties of diffusivity and anisotropy that indicate the integrity of axons. The primary objective of the study was to compare p-NBD patients to healthy controls using diffusion tensor magnetic resonance imaging (DTI-MRI). Methods: The study enrolled parenchymal p-NBD patients who maintained stable disease status for 12 months. Healthy controls were chosen from a population with a similar age and gender distribution. Axial DTI was acquired using single-shot echo-planar imaging. Group analyses were carried out using the track-based spatial statistics tool of FMRIB software library (FSL). Correlations between DTI parameters and clinical outcomes were analyzed in the patient group. Results: We recruited 12 patients with p-NBD and 12 healthy individuals. We found significant fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) differences in the superior longitudinal fasciculus, superior corona radiata, anterior corona radiata, body and genu of the corpus callosum, external capsule, and anterior limb of the internal capsule, mainly in the frontal white matter. Conclusion: Patients with p-NBD exhibit significant DTI alterations in the otherwise normal-appearing frontal association tracts. This study may contribute to a better understanding of the neuropsychological impairment pattern in patients with p-NBD, which is often associated with frontal cognitive networks.
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OBJECTIVE: The main pathophysiological mechanisms in restless legs syndrome (RLS) are known as genetic predisposition, brain iron deficiency, and dopaminergic dysfunction. While some genetic variants and polymorphisms were defined, the genetic basis and etiopathogenesis of RLS remain unclear. We aimed to identify new candidate genes and/or potential biomarkers associated with increased RLS risk. METHODS: Twenty-three patients with RLS, 30 patients with Parkinson's disease (PD), and 27 healthy controls were enrolled. Agilent Human 8X60K Oligo Microarray was used for the identification of gene expression levels in peripheral blood cells. Gene ontology (GO) analysis was used for functional annotation of differentially expressed genes (DEGs). Serum levels of selected DEGs were measured by ELISA for validation. RESULTS: Patients with RLS showed 30 downregulated DEGs compared to healthy controls. Two genes, MTRNR2L10 and MTRNR2L3, involved negative regulation of the execution phase of apoptosis were highlighted in GO analysis. These genes encode humanin-like 10 and 3, respectively, were encoded by these genes, and their levels, along with CSF-1, linked to neurodegeneration, were reduced in RLS patients. Humanin-like 10 and CSF-1 levels correlated with sleep efficiency and N2 sleep duration, while humanin-like 3 levels correlated with mean sleep oxygen saturation during sleep. CONCLUSION: Our study showed that several neuroprotective genes were downregulated in RLS, which may confer susceptibility to neuronal death associated with decreased sleep efficiency. Microarray results differed between RLS and PD patients, suggesting diverse pathogenetic mechanisms. CSF-1, which is involved in iron, dopamine metabolism, and blood oxygenation, appears to partake in RLS pathophysiology.
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BACKGROUND/AIM: Kelch-like protein 11 (KLHL11)-antibody may be found in paraneoplastic neurological disorders presenting with epileptic seizures. The aim of this study was to investigate the prevalence and clinical significance of KLHL11-antibody in epilepsy. PATIENTS AND METHODS: Sera of 42 pediatric and 59 adult patients with seizures of undetermined cause were screened using a cell-based assay. RESULTS: KLHL11-antibody was found in three of 168 control patients with paraneoplastic neurological disorders and four pediatric patients (4-8-year-old, 2 boys/2 girls) with seizures of unknown cause presenting with myoclonic-atonic epilepsy, generalized epilepsy or childhood epilepsy with centrotemporal spikes. In these four cases, seizures continued for 2-7 months, responded promptly and favorably to conventional anti-seizure drugs and did not recur in follow-up durations ranging between 2-5 years. Patients had normal brain MRI findings and motor-mental development before and after seizures. KLHL11-antibody was not detected in adult epilepsy patients with undetermined cause, MOG antibody-positive patients and healthy controls. CONCLUSION: KLHL11-antibody may be detected in pediatric epilepsy patients with a relatively benign disease course.