Introduction Depression is the most common comorbidity of migraine. The brain of migraineurs with depression shows differences compared to migraine only or depression only patients. The comorbidity may affect specific regions such as the periaqueductal gray matter (PAG) which is important in negative emotion regulation and pain modulatory system. Objectives We hypothesized that the alterations in PAG functional connectivity (FC) may play a role in migraineurs vulnerability for depression. Methods A resting-state fMRI was conducted with 34 episodic migraine without aura patients and 41 control subjects. All participants were medication free and they did not have any psychiatric or chronic disorders. Depressive symptoms were measured with Zung Self-Rating Depression Scale. To investigate the relationship between depressive symptoms and PAG functional connectivity, Zung scores were used as covariates in each groups’ PAG-FC analysis using the Statistical Parametric Mapping (SPM12) toolbox in MATLAB environment. Results There were no significant difference between migraine and control group in Zung scores (p=0.394). Negative correlation was found between Zung scores and PAG-FC with thalamus, fusiform gyrus, middle occipital gyrus and calcarine (pFWE<0.05) in migraine group. However, there was no significant correlation between Zung scores and PAG-FC in healthy control group. Conclusions Our results suggest that PAG-FC with emotion and pain processing areas is affected by depressive symptoms in migraine patients, but not in healthy controls. Migraine patients without comorbid depression might have vulnerable neuronal pathways for depressive symptoms. A follow-up of these patients could be interesting to determine whether these connectivity alterations predict the possible comorbid depression. Disclosure Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002, KTIA_13_NAPA-II/14, KTIA_NAP_13-1-2013- 0001, KTIA_NAP_13-2- 2015-0001); 2020-4.1.1.-TKP2020; ERA PerMed (2019-2.1.7-ERA-NET-2020-00005); ÚNKP-21-4-I-SE-15 (DB).

Asymmetric dimethylarginine (ADMA) is associated with endothelial injury. Increased ADMA levels are found in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We set out to assess the ADMA and symmetric dimethylarginine (SDMA) levels in AS, RA, and healthy controls, and in the anti-TNF treated patients with active AS.In 78 AS patients and 29 RA patients who were anti-TNF treatment naive at baseline, along with 23 healthy control subjects, we assessed erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), ADMA, and SDMA. For AS patients, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), back pain VAS and patient's global activity of disease were calculated. After 6 months, we repeated the assessment in 30 out of the 78 AS patients in whom the anti-TNF treatment was initiated.The baseline mean (SD) plasma ADMA concentration of AS patients was 0.64 (0.19) μmol/l and did not differ from controls (0.65 [0.19] μmol/l, p > 0.05). In the RA group, ADMA concentration was higher than in controls (0.77 vs. 0.65 μmol/l, p < 0.05). Both at baseline and at follow-up, ADMA levels correlated positively with BASDAI (R = 0.52, p = 0.02, and R = 0.47, p = 0.04, baseline and follow-up, respectively). Six months of anti-TNF treatment did not influence ADMA concentration (0.51 [0.12] vs. 0.51 [0.11] μmol/l, p = 0.70).An absence of changes in plasma ADMA levels in the anti-TNF treated AS group despite the improvement in disease activity (BASDAI) and inflammation (ESR, CRP) may suggest either a lack of effect, or, even if such an effect were to take place, it needs not imply measurable changes in blood ADMA.

Asymmetric dimethylarginine (ADMA) is associated with endothelial injury. Increased ADMA levels are found in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We set out to assess the ADMA and symmetric dimethylarginine (SDMA) levels in AS, RA, and healthy controls, and in the anti-TNF treated patients with active AS.In 78 AS patients and 29 RA patients who were anti-TNF treatment naive at baseline, along with 23 healthy control subjects, we assessed erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), ADMA, and SDMA. For AS patients, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), back pain VAS and patient's global activity of disease were calculated. After 6 months, we repeated the assessment in 30 out of the 78 AS patients in whom the anti-TNF treatment was initiated.The baseline mean (SD) plasma ADMA concentration of AS patients was 0.64 (0.19) μmol/l and did not differ from controls (0.65 [0.19] μmol/l, p > 0.05). In the RA group, ADMA concentration was higher than in controls (0.77 vs. 0.65 μmol/l, p < 0.05). Both at baseline and at follow-up, ADMA levels correlated positively with BASDAI (R = 0.52, p = 0.02, and R = 0.47, p = 0.04, baseline and follow-up, respectively). Six months of anti-TNF treatment did not influence ADMA concentration (0.51 [0.12] vs. 0.51 [0.11] μmol/l, p = 0.70).An absence of changes in plasma ADMA levels in the anti-TNF treated AS group despite the improvement in disease activity (BASDAI) and inflammation (ESR, CRP) may suggest either a lack of effect, or, even if such an effect were to take place, it needs not imply measurable changes in blood ADMA.

Migraine is one of the most prevalent neurological disorders which is suggested to be associated with dysfunctions of the central nervous system. The purpose of the present study was to detect the altered functional connectivity architecture in the large-scale network of the whole brain in migraine without aura (MWoA). Meanwhile, the brain functional hubs which are targeted by MWoA could be identified. A new voxel-based method named functional connectivity density (FCD) mapping was applied to resting-state functional magnetic resonance imaging data of 55 female MWoA patients and 44 age-matched female healthy controls (HC). Comparing to HC, MWoA patients showed abnormal short-range FCD values in bilateral hippocampus, bilateral insula, right amygdale, right anterior cingulate cortex, bilateral putamen, bilateral caudate nucleus and the prefrontal cortex. The results suggested decreased intraregional connectivity of these pain-related brain regions in female MWoA. In addition, short-range FCD values in left prefrontal cortex, putamen and caudate nucleus were significantly negatively correlated with duration of disease in MWoA group, implying the repeated migraine attacks over time may consistently affect the resting-state functional connectivity architecture of these brain hubs. Our findings revealed the dysfunction of brain hubs in female MWoA, and suggested the left prefrontal cortex, putamen and caudate nucleus served as sensitive neuroimaging markers for reflecting the disease duration of female MWoA. This may provide us new insights into the changes in the organization of the large-scale brain network in MWoA.

: To evaluate the frequency of Medication Overuse Headache (MOH) in the patients with Chronic Daily Headache (CDH) using International Classification of Headache Disorder II Revision (ICHD II R) and International Classification of Headache Disorder 3 Beta (ICHD-3 beta) criteria. We also compare the CHD patients with and without MOH using both the criteria.: Consecutive CDH patients from neurology service between 2014 and 2015 were included. The patients with CDH was categorised to MOH was based on ICHDIIR and ICHD-3 beta criteria. Their demographic and headache characteristics including frequency, duration, severity and disability were noted. Severity of headache was assessed using Visual Analogue Scale (VAS). Predictors of MOH were evaluated by multivariate analysis. Demographic and headache characteristics of CDH patients without MOH were compared with those with MOH.: 202 patients were included whose median age was 32 (range 18–65) years, and 151(74.8%) were females. 12.3% patients fulfilled ICHDIIR criteria for MOH and 46.5% fulfilled ICHD-3 beta criteria. The predictors of MOH were female gender (OR = 3.72; 95% CI 1.72–8.02, p = 0.001), low education level (OR = 1.07, 95%CI 1.02–1.13; p = 0.007) and higher VAS score (OR = 0.67, 95%CI 0.51-0.88; p = 0.004). MOH patients as per ICHD-3 beta criteria had higher education (p = 0.02) and consumed lesser abortive drugs (p = 0.03) as compared with ICHDIIR criteria.: The frequency of MOH increases by four-fold when using ICHD-3 beta criteria instead of ICHDIIR criteria. Females with lower education level predispose to MOH.