The Overexpression of Sonic Hedgehog Associates with Collateral Development and Amelioration of Oxidative Stress in Stroke Patients.

PURPOSE: Sonic hedgehog (SHH) signaling pathway in oxidative stress condition has been acknowledged as a key trigger for angiogenesis and collateral vessel growth in the ischemic brain, and it exerts a protective effect on neuronal cells during oxidative stress. METHODS: A total of sixty patients (n = 30 good collateral profile and n = 30 poor collateral profile) diagnosed with acute cerebral ischemia were enrolled in this study. qRT-PCR was performed to analyze the expression levels of SHH, Gli1, and superoxide dismutase (SOD), genes. Also, the serum levels of oxidative stress markers were determined in experimental groups. RESULTS: The expression levels of SHH and Gli1 genes were significantly (p < 0.05) higher in stroke patients with good collateral circulation compared with those with poor collateral circulation, while SOD gene expression was similar between two groups (p > 0.05). A significantly positive correlation was found between the gene expression of SHH and Gli1 (r = 0.604, p < 0.001), SOD and Gli1 (r = 0.372, p < 0.003) genes. Our findings showed that the serum level of total antioxidant capacity (TAC) and Glutathione (GSH) and SOD enzyme activity was significantly (p < 0.05) increased, while serum total oxidant status (TOS) and malondialdehyde (MDA) levels were significantly (p < 0.05) decreased in patients with good collateral circulation as compared with those with poor collateral circulation. CONCLUSION: Our observations shed light on the association of the SHH/Gli1 signaling pathway with cerebral collateral vessel development following ischemia. Oxidative stress in stroke patients with poor collateral circulation may result in the overexpression of SHH/Gli1 signaling pathway which possibly contribute to oxidative stress attenuation, as well as modulate angiogenesis and collateral vessels development.

The role of Bordetella pertussis in the development of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is one of the most common neurological disorders which main cause is not identified yet. Some studies mentioned the possible role of infectious agents such as chlamydia pneumonia, mycoplasma and also, B. pertussis via asymptomatic nasopharyngeal colonization. The current study aimed to investigate and compared the serum level of B. pertussis antibody and the rate of nasopharyngeal colonization by this pathogen in subjects with and without MS. METHODS: In this case-control study, 109 patients with MS and 114 subjects without MS referred to Sina Hospital in Hamadan in 2019 are studied and compared in terms of serum titer of B. pertussis antibody and nasopharyngeal colonization by this bacterium. Colonization was evaluated using culture and real-time PCR techniques. Data were analyzed using SPSS version 16 with a 95% confidence interval. RESULTS: The serum titer of B. pertussis antibody in case and control groups was 37.8 and 35.1%, respectively (P = 0.74). Culture and real-time PCR techniques revealed no case of nasopharyngeal colonization by B. pertussis. CONCLUSION: There was no difference between B. pertussis antibody titer and the rate of nasopharyngeal colonization between both MS patients and the healthy control group. Therefore, it seems that probably B. pertussis has not a role in MS development.

Assessment of delayed diagnosis and treatment in multiple sclerosis patients during 1990-2016.

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease in the central nervous system. It is one of the major causes of disability in young adults. Early diagnosis and treatment of this disease could decrease later disability and additional costs. In this cross-sectional analytical study, a total of 351 patients were selected from among the multiple sclerosis patients that went to MS clinic or neurologic clinic in 1990-2016. Data were collected and analysed by SPSS v16. This study was conducted on 82.6% females and 17.4% males. Family history of MS was positive in 12.8% of cases. Mean time of onset of symptoms till first medical visit was 3.25 months. Mean time from first medical visit to diagnosis was 14.98 months. Mean time from onset of symptoms till diagnosis was 18.01 months and the mean time from onset of symptoms till initiation of treatment was 18.73 months. Also, 29.3% of cases had delay in first medical visit and 42.2% of cases had delay in diagnosis of MS more than 6 weeks from first medical visit. Overall, delay in first medical visit and diagnosis of MS has decreased over the years. However, there is still delay in diagnosis of MS. Factors associated with delay are low education, male gender, living in rural areas, primary progressive MS, age at MS diagnosis and first clinical symptoms.

The effect of atorvastatin on the common carotid artery intima-media thickness in patients with ischemic stroke.

Occlusion of the initial segment of internal carotid artery is the most common reason for vascular events in the brain. The purpose of this study was to investigate the effect of one-year treatment with atorvastatin on intima-media thickness (IMT) of carotid arteries as a measure of atherosclerosis in stroke patients. In this prospective interventional study, 44 patients with ischemic stroke were investigated. Patients were treated with atorvastatin 40 mg once a day for one year. IMT of carotid arteries was measured by extracranial Doppler ultrasonography in the distal part of the common carotid artery at the beginning of the study, at 6 months and one year of treatment with atorvastatin. The IMT of both right and left carotid arteries decreased after 6- and 12-month atorvastatin treatment. Based on the results of this study, long-term administration of atorvastatin was associated with reduction in carotid artery IMT in patients with ischemic stroke. Such a decrease in IMT may prevent subsequent stroke or cardiovascular events in these patients.

C-Reactive Protein Levels and Clinical Outcomes in Stroke Patients: A Prospective Cohort Study.

BACKGROUND: The C-reactive protein (CRP) level, as an early prognostic factor of functional outcome after stroke, may be of clinical importance. The aim of this study was to determine the prognostic value of CRP on functional outcome and death in stroke patients. METHODS: This prospective study was conducted from 2015 to 2016 in Hamadan province, Iran. Patients with both ischemic and hemorrhagic stroke who were admitted in the first 12 hours were enrolled. The clinical characteristics of the patients were recorded at time of admission as well as on the fourth and the 90th day after stroke. Blood sample was taken and CRP levels were measured at time of admission. RESULTS: From 186 admitted patients, 155 patients remained in this study for analysis. Mean time between stroke onset and admission was 4.42 hours. Mean level of CRP was 20.03 mg/L. CRP levels in 68 patients (43.8%) were 7 mg/L or above. Prevalence of diabetes (P = 0.001), angina pectoris (P = 0.001), death (P = 0.001), pneumonia (P = 0.004), and DVT (P = 0.002) was significantly higher among patients with CRP levels ≥7 mg/L than patients with CRP levels <7 mg/L. A CRP level ≥7 was associated with poor clinical outcome, including the National Institutes of Health Stroke Scale (NIHSS) ≥13 (P = 0.001) as well as modified Rankin Scale (mRS) >2 (P = 0.004) and Barthel Index (BI) <70 on the first (0.047, 0.001), fourth (0.005, 0.001), and 90th day (0.001, 0.001), respectively. CONCLUSION: Our findings indicated that elevated CRP levels in the very early phase of both ischemic and hemorrhagic stroke were associated with poor clinical outcomes and prognosis.

Thrombosis of the Cerebral Veins and Sinuses in Hamadan, West of Iran.

BACKGROUND AND PURPOSE: Cerebral venous sinuses thrombosis (CVST) is an uncommon type of stroke with an incidence of 3-4 cases per million. There have been reports of higher incidence of this disease in Iran. Our objective is to describe the incidence, clinical presentation, predisposing factors, and outcomes of CVST at Sina Hospital in Hamadan, west of Iran. METHODS: This is a prospective, single-center, longitudinal study of all patients referred to Sina Hospital in Hamadan, west of Iran, between May 2009 to May 2015 who were diagnosed with CVST. RESULTS: In this study, 151 patients were included. There were 118 women and 33 men. The mean age was 37.48 years. The mean incidence rate of CVST in the duration of our study was 13.49 per 1 million. Oral contraceptives, the most common risk factor, were used by 55.1% of women and half of these patients had fasting simultaneously. Fifty-eight patients had more than 1 risk factor. After 12 months' follow-up, 73.1% of the patients were functionally independent (mRS score 0-1). Ten percent were dependent. The overall mortality was 16.9%. CONCLUSIONS: The incidence of CVST in Hamadan is higher than the world's average, and overall outcome is worse. It seems that fasting and subsequent dehydration in women with recent use of oral contraceptives make them more susceptible to CVST.

Effect of intravenous sodium valproate vs dexamethasone on acute migraine headache: a double blind randomized clinical trial.

BACKGROUND: Despite the impact of sodium valproate and dexamethasone on migraine headache, the efficacy of the two drugs has not been properly investigated and compared. This trial compared the effect of the two drugs on acute migraine headache. METHODS: This double blind randomized clinical trial was conducted on patients aged 18 to 65 years with acute migraine headache who referred to the emergency departments of Beasat and Farshchian Hospitals in Hamadan, Iran, from April 2012 to June 2014. Patients were randomly assigned to receive a single-dose of either 400 mg sodium valproate or 16 mg dexamethasone plus 50 ml saline normal solution within 15 min intravenously. The severity of headache in the two groups was evaluated at baseline, 0.5 and 2 hours later using the Visual Analog Scale (VAS) on a scale of 0 to 10. RESULTS: Of 104 patients enrolled, 72 patients remained for analysis. The effect of both sodium valproate and dexamethasone on acute migraine headache was statistically significant at 0.5 and 2 hours post-treatment compared to pre-treatment (P=0.001). The severity of headache based on VAS reduced form 8.20 (7.72, 8.68) before treatment to 5.31 (4.74, 5.89) and 3.66 (2.99, 4.33) at 0.5 and 2 hours after treatment, respectively, in patients receiving sodium valproate and from 8.46 (8.05, 8.86) before treatment to 5.46 (4.81, 6.11) and 3.59 (2.84, 4.35) at 0.5 and 2 hours after treatment, respectively, in patients receiving dexamethasone. Both drugs were highly effective in improvement of acute headache in patients without aura. However, sodium valproate significantly improved the acute headache in patients with aura but dexamethasone did not. The severity of headache based on VAS reduced form 8.50 (7.40, 9.60) before treatment to 4.67 (2.40, 6.93) and 3.50 (1.78, 5.22) at 0.5 and 2 hours after treatment, respectively, in patients with aura receiving sodium valproate and from 8.80 (7.76, 9.84) before treatment to 7.20 (4.98, 9.42) and 6.20 (2.43, 9.97) at 0.5 and 2 hours after treatment, respectively, in patients with aura receiving dexamethasone. CONCLUSIONS: This trial indicated that, in overall, intravenous sodium valproate is not superior to intravenous dexamethasone in treatment of acute migraine attacks. However, in patients with aura, only sodium valproate but not dexamethasone is effective in headache relief. This issue needs further investigations. TRIAL REGISTRATION: ClinicalTrials.gov IRCT201202199014N1.

Anti-aquaporin-4 IgG in Patients Presenting with Unilateral Optic Neuritis: A Cohort Study.

BACKGROUND: Optic neuritis (ON) can be the first presentation of multiple sclerosis (MS) or neuromyelitis optica (NMO). Anti-aquaporin-4 IgG (AQP4 IgG) is a highly specific and moderately sensitive biomarker for NMO. This study was designed to assess the rate of seropositivity for AQP4 IgG, and the short-term outcome of patients presenting with single isolated ON (SION). METHODS: A cohort of 41 consecutive patients experiencing severe (< 20 / 200) SION (not fulfilling the diagnostic criteria for MS or NMO), was prospectively recruited. Blood sampling was carried out immediately after the diagnosis of ON, and AQP4 IgG was tested qualitatively, using an indirect immunofluorescence kit. After clinical and paraclinical investigations, all the patients were followed up for a short-term period of at least 18 months. RESULTS: The seroprevalence among the initial ON patients was 9.7% (4 / 41). The short-term conversion rate to MS and NMO was estimated to be about 7.3 and 4.9%, respectively. The conversion rate to NMO in initially seropositive patients was greater than that for the whole cohort [2 / 4 (50%) vs. 2 / 41 (4.9%); P = 0.035; Odds ratio: 19.5, 95% confidence interval: 1.73 to 219.50]. CONCLUSION: AQP4 IgG seropositive SION patients were more likely to develop NMO in comparison to the total SION population. Further studies, with a longer follow-up period and larger sample sizes are warranted to assess the clinical and prognostic value of assessing AQP4 IgG in SION.

The G-308A promoter variant of the tumor necrosis factor-alpha gene is associated with migraine without aura.

Migraine is considered to be a polygenic multifactorial disease with various environmental and genetic etiologies. Tumor necrosis factor-alpha (TNF-alpha), a potent immunomodulator and pro-inflammatory cytokine, has been implicated in many pathological processes in brain. The hypothesis of this study was that migraine without aura (MWA) might be associated with TNF-alpha (-308) polymorphism, resulting in increased TNF-alpha production. Genotyping was performed on DNA extracted from peripheral leukocytes by PCR-SSP method in 221 patients with WMA and 183 healthy control subjects from Iranian population. The results showed that the frequency of -308 A variant allele was higher in MWA than in the control group (40.6% versus 22.3%, OR 3.73, 95% CI 2.4-5.82, p<0.0001). TNF-alpha GA heterozygous genotype, high producer, was significantly more prevalent in patients with MWA than controls (74% versus 44.7%, p<0.0001) whilst the low producer GG homozygous genotype was less frequent in patients compared with controls (22.4% versus 55.3%, p<0.0001). The logistic regression analysis showed a significant association for TNF-alpha (-308A) female allele carriers with MWA at reproductive ages (OR 2.56; 95% CI, 1.57-4.16, p<0.0001) when compared with their matched control subjects. In conclusion, this study demonstrates an association of tumor necrosis factor-alpha (-308A) carriage with MWA, suggesting that carrying a high responder TNF-alpha-308A allele may be a genetic factor in increasing the susceptibility to develop MWA.