Exploring the Psychiatric Manifestations of Primary Sjögren's Syndrome: A Narrative Review.

Background: Primary Sjögren's syndrome (pSS) is recognized for its autoimmune origin. Its hallmark symptoms, dry eyes and mouth, result from glandular inflammation. Prior literature indicates that pSS not only affects the peripheral system but also involves the central nervous system (CNS), giving rise to various neuropsychiatric symptoms. However, there is limited published research on the psychiatric comorbidities in individuals with pSS. Methods: A comprehensive search was conducted on PubMed and Google Scholar for this narrative review. The search spanned from inception until August 2023. Its aim was to locate studies focusing on the psychiatric manifestations of pSS and the potential underlying mechanisms. Results: The most commonly reported psychiatric complications among these individuals are depression and cognitive dysfunction. Other psychiatric manifestations that have been reported in pSS individuals include anxiety, sleep disorders, psychosis, catatonia, bipolar disorder, and obsessive-compulsive disorder. Conclusion: In conclusion, patients with pSS often display multiple psychiatric symptoms. These symptoms can significantly impair functioning and reduce quality of life. Hence, prompt diagnosis and management are crucial.

Antipsychotic agents in anxiety disorders: An umbrella review.

BACKGROUND: Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. OBJECTIVE: The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436). METHODS: An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. RESULTS: The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD). CONCLUSIONS: This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.

Pathophysiological mechanisms of post-myocardial infarction depression: a narrative review.

Myocardial infarction (MI) can have significant physical and mental consequences. Depression is a prevalent psychiatric condition after MI which can reduce the quality of life and increase the mortality rates of patients. However, the connection between MI and depression has remained under-appreciated. This review examines the potential connection between depression and MI by overviewing the possible pathophysiologic mechanisms including dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, coagulation system dysfunction, inflammation, environmental factors, as well as, genetic factors. Furthermore, depression can be an adverse event of medications used for MI treatment including beta-blockers, statins, or anti-platelet agents. The need for early detection and management of depression in patients with MI is, therefore, crucial for improving their overall prognosis. Adherence to treatments and regular follow-up visits can ensure the best response to treatment.

An umbrella review on the use of antipsychotics in anxiety disorders: A registered report protocol.

Anxiety disorders, including panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), agoraphobia, and specific phobia, are among the most common psychiatric disorders. Although the traditional pharmacologic treatments for anxiety included barbiturates and then benzodiazepines, the introduction of tricyclic antidepressants, followed by the selective serotonin reuptake inhibitors (SSRIs), marked a tidal shift in the treatment of anxiety. Although not approved for treatment of anxiety disorders (with the exception of trifluoperazine) there is ongoing off-label, unapproved use of both first-generation "typical" antipsychotics (FGAs) and second-generation or "atypical" antipsychotics (SGAs) for anxiety. Although there have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of these reviews focused on SGAs, primarily the use of quetiapine in GAD. Given that there is little known about the potential benefits and short-and long-term risks of using antipsychotics in anxiety, there is a need for an umbrella review of systematic reviews and meta-analyses of the use of both FGAs and SGAs in anxiety disorders. The specific aims of this study are as follows: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs) and other non-antipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects; and (3) Evaluate the short- and long-term risks and side effects of prescribing antipsychotics in anxiety disorders. The review is registered on PROSPERO (CRD42021237436). Since data extraction has not begun, there is not preliminary data to share.

Clinical and imaging outcomes after intrathecal injection of umbilical cord tissue mesenchymal stem cells in cerebral palsy: a randomized double-blind sham-controlled clinical trial.

BACKGROUND: This study assessed the safety and efficacy of intrathecal injection of umbilical cord tissue mesenchymal stem cells (UCT-MSC) in individuals with cerebral palsy (CP). The diffusion tensor imaging (DTI) was performed to evaluate the alterations in white-matter integrity. METHODS: Participants (4-14 years old) with spastic CP were assigned in 1:1 ratio to receive either UCT-MSC or sham procedure. Single-dose (2 × 107) cells were administered in the experimental group. Small needle pricks to the lower back were performed in the sham-control arm. All individuals were sedated to prevent awareness. The primary endpoints were the mean changes in gross motor function measure (GMFM)-66 from baseline to 12 months after procedures. The mean changes in the modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also assessed. Secondary endpoints were the mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR). RESULTS: There were 36 participants in each group. The mean GMFM-66 scores after 12 months of intervention were significantly higher in the UCT-MSC group compared to baseline (10.65; 95%CI 5.39, 15.91) and control (ß 8.07; 95%CI 1.62, 14.52; Cohen's d 0.92). The increase was also seen in total PEDI scores (vs baseline 8.53; 95%CI 4.98, 12.08; vs control: ß 6.87; 95%CI 1.52, 12.21; Cohen's d 0.70). The mean change in MAS scores after 12 months of cell injection reduced compared to baseline (-1.0; 95%CI -1.31, -0.69) and control (ß -0.72; 95%CI -1.18, -0.26; Cohen's d 0.76). Regarding CP-QoL, mean changes in domains including friends and family, participation in activities, and communication were higher than the control group with a large effect size. The DTI analysis in the experimental group showed that mean FA increased (CST 0.032; 95%CI 0.02, 0.03. PTR 0.024; 95%CI 0.020, 0.028) and MD decreased (CST -0.035 × 10-3; 95%CI -0.04 × 10-3, -0.02 × 10-3. PTR -0.045 × 10-3; 95%CI -0.05 × 10-3, -0.03 × 10-3); compared to baseline. The mean changes were significantly higher than the control group. CONCLUSIONS: The UCT-MSC transplantation was safe and may improve the clinical and imaging outcomes. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03795974 ).

Psychometric Properties of Mobile Phone Abuse (MPA): Exploratory and Confirmatory Factor Analysis in Student Mobile Users.

Objective: Smartphone is an important technology device in our lifestyle. It has an important part of our daily lives, but it also has a negative effect, such as cell phone dependency. This research aimed to evaluate the psychometric properties of mobile phone abuse (MPA) in the Iranian population. Method: In this study, data were chosen from 1100 participants who were studying in Tehran universities. The principal version of the scale was translated into Persian using the back translation method. All attendees completed Demographic Questionnaire, MPA Questionnaire, and Mobile Phone Problematic Use Scale (MPPUS). Eventually, a clinical interview (based on the fifth version of DSM) was done for all the participants. For data analysis, internal and external consistency, factor analysis, construct validity and confirmatory factor analysis (CFA) were used. Statistically, less than 0.05 were considered to be significant. Results: According to expert judgments, content validity index was satisfactory. Furthermore, the reliability of the questionnaire was confirmed with Cronbach's α of 0.90 and test-retest reliability of 0.56 after 3 weeks. The best cutoff point for this questionnaire (MPA) was 46. Also, 4 factors were extracted by principal components method and varimax rotation: "excessive use of cell phone," "addictive use of social networks," "mood modification," and "preoccupation" for both male and female students. Conclusion: MPA could be used in studies on the evaluation of mobile phone addiction. This can be a stepping stone towards the identification of problems and improvement of students' mobile phone abuse.

Epidemiology of Psychotic Disorders Based on Demographic Variables in Iranian Children and Adolescents.

Objective: Psychosis is still among the most debilitating and severe mental disorders. The main objective of the present study was to investigate the estimated prevalence of psychotic disorders and finding the main predictors of psychotic disorders among Iranian children and adolescents. Method : Our total sample consisted of 30 553 individuals (49% males and 51%females) from 30 provinces of Iran, aged between 6 and 18 years, who were selected via cluster sampling method from rural and urban areas of all provinces. The data were analyzed using descriptive statistical analysis and multiple logistic regression method. Results: The results of multiple regression analysis showed that prevalence estimate of psychotic disorders was 0.25%. It was 0.3% and 0.2% in males and females, respectively. The age of 10-14 (OR = 2.24; 95% CI, 1.11-4.55) and the age of 15-18 (OR = 3.42; 95% CI, 1.74-6.75) were significant positive predictors, whereas none of the demographic variables were predictors for psychotic symptoms. Conclusion: This research highlights the main predictors of psychosis in children and adolescents. The study design also allowed a better understanding of predictors of psychotic disorders. The assessment of the prevalence of psychiatric disorders, particularly their comorbidities, may help to prevent mental illnesses in children and adolescents.

The Association between Behavioral Problems with Self-Esteem and Self-Concept in Pediatric Patients with Thalassemia.

Objective: High prevalence of behavioral and psychological disorders in children with thalassemia can be associated with a decrease in the self-esteem of patients and can completely alter the person's self-concept. The aim of this study was to determine the prevalence of behavioral problems and its relationship with self-esteem and self-concept in patients with thalassemia major aged 6 to 18 years. Method : In a cross-sectional study, 30 patients with thalassemia major at the age of 6 to 18 years were enrolled. behavioral problems, self-esteem, and self-concept were evaluated by the child's behavioral check list at the ages of 6 to 18 years (CBCL 6-18), the Coopersmith's Self-Esteem Inventory, and the Piers-Harris Children's Self-Concept Scale. Results: A total of 10.0% of patients had behavioral disorders, 3 (10.0%) desirable self-esteem, 15 (50.0%) moderate self-esteem, and 12 (40.0%) poor self-esteem. There was a strong but adverse correlation between behavioral disorder score and both self-esteem score (correlation coefficient equal to -0.886, p value = 0.001) and self-concept score (correlation coefficient equal to -0.498, p value = 0.001), and thus those patients with behavioral disorder had less appropriate self-esteem and self-concept. Conclusion: The incidence of behavioral disorders is associated with decreased self-esteem and poor self-concept in these patients. Therefore, improvement in behavioral disorders can be expected by improving self-esteem and self-concept in such patients.

Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study.

BACKGROUNDS: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. METHODS: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements. RESULTS: We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up. CONCLUSION: Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.

The prevalence of post-traumatic stress disorder related symptoms in Coronavirus outbreaks: A systematic-review and meta-analysis.

BACKGROUND: Infectious disease outbreaks affect physical and mental health of humans worldwide. Studies showed that the prevalence of post-traumatic stress disorder (PTSD) symptoms increased in these conditions. This systematic-review and meta-analysis aimed to assess the prevalence of PTSD related symptoms in coronavirus outbreaks. METHODS: Systematic search of literature was conducted in Scopus, Embase, PubMed, and Web of Science. Google Scholar and Grey literature including conference proceedings were also checked. Published articles from November 1, 2012 until May 18, 2020 were searched. Subgroup analysis, meta-regression and sensitivity analysis were also conducted to assess heterogeneity. RESULTS: We found 38 articles with 19,428 individuals met the eligibility criteria. Of these papers, 35 studies were included in meta-analysis. The prevalence of PTSD symptoms was estimated to be about 18% (95%CI: 15% to 20%). These symptoms were more frequent in cohort studies (29%) compared to cross-sectional (15%) and case-control (11%) studies. Prevalence rates of PTSD symptoms in MERS (36%) outbreaks were higher than SARS (18%) and COVID-19 (9%) outbreaks. Meta-regression showed that the geographical location of study was the source of heterogeneity (R2: 19.8%, P-value: 0.003). Meta-analysis reported that about three in every ten survivors of coronavirus infection, about two in every ten healthcare workers, and about one in every ten individuals of general population experienced PTSD symptoms in outbreaks. LIMITATIONS: PTSD cannot be objectively assessed and this can lead to information bias of included studies. CONCLUSION: PTSD symptoms are shown to be common in coronavirus outbreaks. Mental care should be, therefore, considered in the present COVID-19 pandemic.

The Trend of Interpersonal Violence Mortality at National and Provincial Levels in Iran From 1990 to 2015.

Interpersonal violence (IPV) is a major public health concern with a significant impact on physical and mental health. This study was designed to evaluate age-sex-specific IPV mortality trends and the assault mechanisms (firearm, sharp objects, and other means), at national and provincial levels, in Iran. We used the Iranian Death Registration System (DRS) and the population and housing censuses in this analysis. Spatio-temporal and Gaussian Process Regression methods were used to adjust for inconsistencies at the provincial level and to integrate data from various sources. After assessing their validity, all records were reclassified according to the International Classification of Diseases, 10th Revision (ICD-10). All ICD-10 codes were then mapped to Global Burden of Disease (GBD) 2013 coding. More than 700 individuals died due to IPV in 1990 and more than twice this number in 2015. The IPV mortality age-standardized rate, per 100,000, increased from 1.62 (95% Uncertainty Interval [UI] = [0.96, 2.75]) in 1990 to 1.81 [1.15, 2.89] in 2015. Among females, the age-standardized mortality rate at national level per 100,000 due to IPV was 1.27 [0.66, 2.43] in 1990 and decreased to 1.08 [0.60, 1.96] in 2015. Among males, the age-standardized mortality rate was 1.96 [1.25, 3.09] in 1990 rising to 2.54 [1.70, 3.82] in 2015. Data from provinces revealed that during the period of our study, Hormozgan province had the largest increase of IPV among females, and Fars province had the largest increase of IPV among males. Conversely, the largest decrease was detected in West Azarbaijan and Qom provinces in females and males, respectively. This study showed a wide variation in the incidence and trends of IPV in Iran by age, sex, and location. The study has provided valuable information to reduce the burden of IPV in Iran and a means to monitor future progress through repeated analyses of the trends.

The safety and efficacy of transcranial direct current stimulation as add-on therapy to fluoxetine in obsessive-compulsive disorder: a randomized, double-blind, sham-controlled, clinical trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is an anxiety disorder that causes impairment in daily activities. This study aimed to assess the safety and efficacy of transcranial direct current stimulation (tDCS) as adjunctive therapy with fluoxetine in individuals diagnosed with moderate to severe OCD. METHODS: This is a randomized, double-blind sham-controlled trial. Individuals with OCD who had baseline Yale-Brown obsessive-compulsive scale (Y-BOCS) of > 15 were enrolled. Eligible cases were randomly assigned in 1:1 ratio to receive either 20-min-period of stimulation with tDCS and fluoxetine (experimental arm) or fluoxetine only (sham control arm). The anodal electrode of tDCS was placed over the left dorsolateral prefrontal cortex (Fp3) and the cathodal electrode was placed over the right orbitofrontal cortex (F8). Two mA electrical stimulation with the tDCS was used for 20 min in individuals of experimental group. In the control group, electrodes were placed and stimulation was administered for 30 s to induce the same skin sensation as in experimental group. This procedure was performed three times per week for 8 weeks. Y-BOCS test was assessed at baseline, week 4 (after 12th stimulation), week 8 (after 24th stimulation), and 1 month after the last stimulation. The primary endpoints were the mean changes in Y-BOCS total score from baseline to the last visit. The secondary endpoints were the mean changes in obsession and compulsion sub-scores from baseline to the last visit. Adverse events were also assessed. Mixed design repeated measures analysis of variance assessed the endpoints. RESULTS: Sixty individuals (30 in each group) were participated. All individuals in control group and 28 cases in experimental arm completed the trial. The mean Y-BOCS (F(1.85) = 30.83; P < 0.001), OCD obsession (F(2.23) = 25.01; P < 0.001), and compulsion (F(2.06) = 10.81; P < 0.001) scores decreased significantly during the study. No statistical differences were, however, detected between experimental and control groups (P > 0.05). The tDCS was well tolerated and no major adverse events were reported. CONCLUSION: This study showed that among individuals with moderate to severe OCD, there was no significant difference regarding OC symptoms between cases used tDCS as adjunctive therapy with fluoxetine and individuals used fluoxetine only. TRIAL REGISTRATION: IRCT2017030632904N1 . Registered 14 July 2017, http://irct.ir/user/trial/44193/view.

Global Prevalence of Posttraumatic Stress Disorder (PTSD) during and after Coronavirus Pandemic: A Study Protocol for a Systematic Review and Meta-Analysis.

Objective: Studies conducted on severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 epidemics have shown PTSD can occur during and after infectious diseases. However, more studies are needed to explore PTSD during and after COVID-19 outbreak. The objective of this study is to provide a protocol of systematic review and meta-analysis to report the global prevalence of PTSD during and after coronavirus pandemics among general population, health care workers, survivors, or patients with coronaviruses. Method : We include all studies that reported the prevalence of PTSD during and after coronavirus pandemics and search databases, including Web of Science, PubMed, Scopus, Embase, and Google Scholar from first of November 2002 to May 18, 2020. Two authors independently use relevant checklists to quality assessment of the included studies and extract data. We use the graphical methods and fixed or random effect models to aggregate prevalence estimates. Also, we will assess heterogeneity between the included studies using the I2 heterogeneity statistic and use subgroup and sensitivity analysis to assess the sources of heterogeneity. Discussion: We infer that PTSD is a common experience during and after infectious disease pandemics, especially COVID-19. The findings of this study can be used by health policymakers and other stakeholders and will provide a path to future studies.

The trend of fall-related mortality at national and provincial levels in Iran from 1990 to 2015.

Falls are one of the major causes of unintentional injuries. Understanding the epidemiology of fall-related mortality helps to identify the root causes of this event and planning preventive strategies to inhibit falls. The aim of this study was to assess the trend of fall-related mortality rate and its epidemiological patterns based on sex and age-groups at national and subnational levels in Iran during the years 1990 to 2015. All data were gathered from Death Registration Systems, cemetery databases of Tehran and Isfahan, the Demographic and Health Survey of 2000 and three rounds of national population and housing censuses. The age-standardized death rate (ASDR) due to falls per 100,000 people decreased from 2.61 (95% Uncertainty Interval (UI): 1.94-3.51) in 1990 to 2.13 (1.62-2.80) in 2015 at national level. Males were at higher risk of death due to falls than females. Our data showed that the elderly population was at higher risk of death due to falls and individuals less than 4-year old had the highest fall-related mortality rate among children and adolescents. Our data should be used to accelerate interventions to reduce fall-related mortality.

Social anxiety disorder among children and adolescents: A nationwide survey of prevalence, socio-demographic characteristics, risk factors and co-morbidities.

BACKGROUND: Social anxiety disorder is a frequent psychiatric disorder. We aimed to estimate the life-time prevalence, socio-demographic characteristics, risk factors and co-morbidities of this condition among children and adolescents. METHODS: This was a cross sectional national survey conducted in Iranian individuals aged 6 to 18 years. Face-to-face household interviews were performed by trained clinical psychologists. The Farsi version of the kiddie schedule for affective disorders and schizophrenia for school-age children/present and lifetime version (K-SADS-PL) was administered to estimate the SAD prevalence. Parental personality traits and their psychopathologies were also obtained using Millon clinical multiaxial inventory, third edition (MCMI-III) to find the possible risk factors. RESULTS: From 29,878 participants, 585 individuals were diagnosed with SAD and weighted lifetime prevalence of 1.8% was observed. The odds of this condition was significantly higher among older adolescents (odds ratio (OR):1.47; 95% confidence interval(CI): 1.11-1.95) and individuals with paternal history of psychiatric hospitalization (OR: 2.96; 95%CI: 1.29-6.79). Higher means of persistent depression disorder (OR: 1.009; 95%CI: 1.000-1.018) and melancholic personality trait (OR: 1.007; 95%CI: 1.001-1.014) in mothers as well as schizophrenia spectrum (OR: 1.014; 95%CI: 1.001-1.027) and anxiety (OR: 1.010; 95%CI: 1.010-1.021) in fathers were statistically associated with higher odds of SAD in their children. Other anxiety disorders and behavioral disorders were the most prevalent co-morbidities. LIMITATIONS: The cross-sectional analysis does not enable analyses of possible causal associations. Lacking control group and follow-up periods were other major limitations that should be resolved in future studies. CONCLUSION: Clinicians and researchers need to continue studying this condition at all levels and in all developmental periods.

Cinnarizine and sodium valproate as the preventive agents of pediatric migraine: A randomized double-blind placebo-controlled trial.

BACKGROUND: Few migraine preventive agents have been assessed in a pediatric population. We evaluated the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in children and adolescents. METHODS: We carried out a randomized double-blind placebo-controlled trial in the Children's Medical Center and Sina hospital, Tehran, Iran. Eligible participants were randomly assigned in 1:1:1 ratio via interactive web response system to receive either cinnarizine, sodium valproate, or placebo. The primary endpoints were the mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial. The secondary endpoint was the efficacy of each drug in the prevention of migraine. The drug was considered effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline. Safety endpoint was adverse effects that were reported by children or their parents. RESULTS: A total of 158 children participated. The frequency of migraine attacks significantly reduced compared to baseline in cinnarizine (difference: -8.0; 95% confidence interval (CI): -9.3 to -6.6), sodium valproate (difference: -8.3; 95% confidence interval: -9.3 to -7.2), and placebo (difference: -4.4; 95% confidence interval: -5.4 to -3.4) arms. The decrease was statistically greater in cinnarizine (difference: -3.6; 95% confidence interval: -5.5 to -1.6) and sodium valproate (difference: -3.9; 95% confidence interval: -5.8 to -1.9) arms, compared to placebo group. Children in all groups had significant reduction in intensity of episodes compared to baseline (cinnarizine: -4.6; 95% confidence interval: -5.2 to -4.0; sodium valproate: -4.0; 95% confidence interval: -4.8 to -3.3; placebo: -2.6; 95% confidence interval: -3.4 to -1.8). The decrease was statistically greater in cinnarizine (difference: -2.0; 95% confidence interval: -3.2 to -0.8) and sodium valproate (difference: -1.5; 95% confidence interval: -2.7 to -0.3) arms, compared to the placebo group. Seventy-one percent of individuals in the cinnarizine group, 66% of cases in the sodium valproate group, and 42% of people in the placebo arm reported more than 50% reduction in episodes at the end of the trial. The odds ratio for >50% responder rate was 3.5 (98.3% confidence interval: 1.3 to 9.3) for cinnarizine versus placebo and 2.7 (98.3% confidence interval: 1.0 to 6.9) for sodium valproate versus placebo. Nine individuals reported adverse effects (three in cinnarizine, five in sodium valproate, and one in the placebo group) and one case in the sodium valproate group discontinued the therapy due to severe sedation. CONCLUSION: Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents. Trial registration: IRCT201206306907N4.

Levetiracetam for prophylactic treatment of pediatric migraine: A randomized double-blind placebo-controlled trial.

INTRODUCTION: Few drugs are available for migraine prophylaxis in children. Levetiracetam is a broad-spectrum anti-seizure drug that has been suggested to be effective in reducing adult migraine episodes. We assessed the safety and efficacy of levetiracetam in the prevention of pediatric migraine. METHODS: A randomized double-blind placebo-controlled trial was performed. Eligible participants were aged 4-17 years old with at least four migrainous episodes monthly or had severe disabling or intolerable episodes. Primary endpoints were the mean changes in monthly frequency and intensity of headaches from the baseline phase to the last month of the double-blind phase. Safety endpoint was the adverse effects reported. RESULTS: Sixty-one participants (31 taking levetiracetam and 30 taking placebo) completed the study. All had a significant reduction in frequency and intensity of episodes that was significantly greater in the levetiracetam arm. Sixty eight percent of individuals in the treatment group reported more than 50% reduction of episodes at the end of the trial compared with 30% in the placebo group (p-value: 0.007). Irritability, day-time sedation, and mild tic were reported. CONCLUSION: Levetiracetam may be useful in migraine prevention and may decrease migraine episodes and severity. TRIAL REGISTRATION: The study is prospectively registered with Iranian Registry of Clinical Trials; IRCT.ir, number IRCT2017021632603N1.

Seizures as a clinical manifestation in somatic autoimmune disorders.

The risk of epileptic seizures seems increased in several systemic autoimmune disorders including systemic lupus erythematosus, type 1 diabetes mellitus, myasthenia gravis, celiac disease, rheumatoid arthritis, Hashimoto's encephalopathy, psoriasis, multiple sclerosis, neuromyelitis optica, and bullous pemphigoid. Immune dysfunction may be partly responsible for this association. Elevated levels of pro-inflammatory cytokines, autoantibodies seen in these autoimmune disorders and antibodies against neuronal antigens may contribute to the etiopathogenesis of seizures and epilepsy associated to immune conditions. Other unknown factors, the effect of different co-morbid conditions of epilepsy as well as shared risk factors such as common etiological factors, environmental triggers, or a common genetic predisposition may also explain the association. We review different autoimmune disorders which may present with co-morbid seizures and discuss possible underlying mechanisms of this co-occurrence focusing on a potential role of immune system dysfunction.