Anti-inflammatory activity of bupropion through immunomodulation of the macrophages.

Depression might manifest itself with a chronic inflammation in different tissues and organs independent of the central nervous system. Psoriasis, Crohn's disease, and fibromyalgia are among these disorders accompanying the depression. The treatment options for these conditions are a combination of the anti-depressants and anti-inflammatory agents. Bupropion has been widely utilized as an anti-depressant. It has been preferred among the patients with Crohn's disease and psoriasis due to its anti-inflammatory role, as well. In this study, we aimed to decipher its target in the immune system. Macrophages were activated in the presence of LPS and increasing concentrations of the bupropion. TNF-α, IL-6, GM-CSF, and IL-12p40 cytokines' production levels were measured by ELISA to compare it to the control groups. These cytokines have been associated with the aggressive inflammation in different tissues. Moreover, p38 and PI3K proteins' phosphorylated levels were measured to examine whether bupropion acts through these pathways or not. Our results suggest that bupropion had anti-inflammatory action on the activated macrophages and its mechanism of action was partially dependent on p38 but independent of PI3K pathways.

Assessment of safety and feasibility of non-invasive vagus nerve stimulation for treatment of acute stroke.

BACKGROUND: Non-invasive vagus nerve stimulation (nVNS) using a hand-held stimulator placed on the neck is an FDA-approved treatment for primary headache disorders. The safety of nVNS is unknown in stroke patients. OBJECTIVE: To assess the safety and feasibility of nVNS for the acute treatment of stroke. METHODS: TR-VENUS (clinicaltrials.gov identifier NCT03733431) was a randomized, sham-controlled, open-label, multicenter trial conducted in patients with acute ischemic stroke (IS) or intracerebral hemorrhage (ICH). Patients were randomly assigned to standard-dose nVNS, high-dose nVNS, or sham stimulation. The primary endpoint was a composite safety outcome defined as bradycardia or reduction in mean arterial blood pressure during treatment or progression of neurological or death within 24 h of treatment. The feasibility endpoints were the proportion of eligible subjects receiving nVNS within 6 h of symptom onset and the proportion completing all pre-specified treatment doses. Efficacy assessments included infarct growth from baseline to 24 h after treatment. RESULTS: Sixty-nine patients (61 IS, 8 ICH) completed the study. The composite safety outcome was achieved in 32.0% in sham and 47.7% in nVNS group (p = 0.203). Treatment was initiated in all but two randomized patients. All dosed subjects received 100% of prespecified stimulations. A non-significant reduction in infarct growth was observed in the high-dose nVNS group (184.2% in sham vs. 63.3% in high-dose nVNS; p = 0.109). CONCLUSIONS: The results of this study suggest that nVNS may be safe and feasible in the setting of acute stroke. These findings support further development of nVNS as a potential treatment for acute ischemic stroke.

Study of Transesophageal Echocardiography in Young Patients with Cryptogenic Stroke: Prevalence of Patent Foramen Ovale and Interpretation of the RoPE Score.

OBJECTIVE: Cryptogenic stroke (CS) is considered to be the most common stroke subtype in young patients. The Risk of Paradoxical Embolism (RoPE) score is a tool that stratifies patients with CS according to the probability of patent foramen ovale (PFO). The aim of this retrospective study is to determine the prevalence of PFO in young patients with transesophageal echocardi- ography (TEE) and to evaluate the role of RoPE score in PFO-related strokes. METHODS: The medical records of patients with acute arterial ischemic stroke, who underwent TEE between 2016 and 2020, were reviewed. Patients aged 18-55 years were included in the study. Presence of PFO, PFO characteristics, presence of atrial septal aneurysm (ASA) were detected by examining the image records of the patients from the archive system. RoPE score was calculated for all patients as determined in the literature. RESULTS: Totally, 50 CS patients were included in the study (mean age: 39.6±9.4 years). PFO was detected in 19 (38%) patients and it was the most common cardiac abnormality in CS patients. ASA was detected in 7 (14%) patients. The mean RoPE score in patients with PFO was higher than patients without PFO, although it did not reach statistical significance (7.68±1.1 versus 6.77±1.9 P = .07). Eighteen of 19 patients with PFO had a RoPE score ≥7. CONCLUSION: In our study, PFO prevalence in the CS patients was higher than normal popula- tion. In patients with cryptogenic stroke, the RoPE score can help determine the probability of PFO related stroke and which patients should undergo TEE.

A Rare Cause of Recurrent Cerebral Ischemia and Syncope: Eagle Syndrome.

Eagle syndrome is defined as symptomatic elongation of the styloid process or calcification of the stylohyoid and stilomandibular ligament. The syndrome was described by WW Eagle in 1937. The styloid process is located between the internal and external carotid arteries and laterally in the tonsillar fossa. Patients with cerebrovascular ischemia causing syncope or hemiparesia due to Eagle syndrome are rarely published in the literature. The authors presented a patient with recurrent cerebrovascular attacks due to long styloid process.

A database for screening and registering late onset Pompe disease in Turkey.

The aim of this study was to search for the frequency of late onset Pompe disease (LOPD) among patients who had a myopathy with unknown diagnosis registered in the pre-diagnostic part of a novel registry for LOPD within a collaborative study of neurologists working throughout Turkey. Included in the study were 350 patients older than 18 years who have a myopathic syndrome without a proven diagnosis by serum creatine kinase (CK) levels, electrodiagnostic studies, and/or muscle pathology, and/or genetic tests for myopathies other than LOPD. Acid alpha glucosidase (GAA) in dried blood spot was measured in each patient at two different university laboratories. LOPD was confirmed by mutation analysis in patients with decreased GAA levels from either both or one of the laboratories. Pre-diagnostic data, recorded by 45 investigators from 32 centers on 350 patients revealed low GAA levels in a total of 21 patients; from both laboratories in 6 and from either one of the laboratories in 15. Among them, genetic testing proved LOPD in 3 of 6 patients and 1 of 15 patients with decreased GAA levels from both or one of the laboratories respectively. Registry was transferred to Turkish Neurological Association after completion of the study for possible future use and development. Our collaborative study enabled collection of a considerable amount of data on the registry in a short time. GAA levels by dried blood spot even from two different laboratories in the same patient may not prove LOPD. LOPD seemed to be rarer in Turkey than in Europe.

Cytokine polymorphism in patients with migraine: some suggestive clues of migraine and inflammation.

OBJECTIVE: There are contrasting results obtained in migraineurs concerning the levels and the role of both pro-inflammatory and anti-inflammatory cytokines. In this study, the association of the occurrence and clinical characteristics of migraine with the polymorphisms of tumor necrosis factor alpha (TNF-alpha) -308 G/A (rs1800629), interleukin-1alpha (IL-1alpha) +4845 G/T (rs17561), IL-1beta+3953 C/T (rs1143634) and interleukin-1 receptor antagonist variable number tandem repeat (IL-1RA VNTR) genes were studied. We also investigated the genetic linkage between these genes. DESIGN, SETTING, PATIENTS: Sixty-seven patients with migraine without aura (MwoA) and 96 unrelated, age- and sex-matched migraine-free, healthy control subjects from the same geographic area were investigated. RESULTS: We observed significant differences in the genotypic distribution of the TNF-alpha-308 G/A and IL-1beta+3953 C/T polymorphism for migraineurs compared with controls (P = 0.004). Frequency of the TNF-alpha-308 GG genotype was higher in the control group than MwoA group (82.1% vs 55.2%). Differences in the distribution of the allele frequencies were also observed, being the TNF-alpha-308 G allele overrepresented in control group and TNF-alpha-308 A allele in MwoA group. In addition, there was a significant increase of the IL-1beta+3953 T allele in MwoA cases compared with controls (P = 0.004). CONCLUSIONS: In conclusion, the present results indicate the possible contribution of TNF-alpha and IL-1beta gene polymorphisms to migraine headache generation in MwoA patients.