Efficacy of Probiotics in Improving Motor Function and Alleviating Constipation in Parkinson's Disease: A Randomized Controlled Trial.

Background: Parkinson's disease (PD) is one of the common neurodegenerative diseases, and there has been an increasing interest in the potential role of intestinal dysbiosis in its pathogenesis and related gastrointestinal complications such as constipation. Objectives: This study aims to evaluate the effects of multi-strain probiotics on constipation and motor function in PD patients. Methods: This study was a blinded, randomized controlled trial (RCT) that involved 27 PD patients who were diagnosed with constipation according to the ROME IV criteria for functional constipation. The primary outcome measured before and after the intervention in both the placebo and probiotic groups was the frequency of defecation. Secondary outcomes evaluated were laxative use, sense of complete evacuation, Bristol Stool Scale for consistency, and Unified Parkinson's Disease Rating Scale (UPDRS) scale. The study lasted for eight weeks. Both groups also were educated about lifestyle modification. Results: Of 30 included patients (15 in each group), 13 were women, and 17 were men. Three patients dropped out of the study. Between-group analysis showed that the frequency of bowel movements significantly increased in the probiotic group 4 [3 - 5] in comparison with 2 [2 - 3] in placebo (P = 0.02). Stool consistency also improved in the probiotic group (P = 0.04). However, there were no significant differences in other outcomes. The within-group analysis showed improvement in stool consistency in both probiotics and placebo groups (P = 0.01 and P = 0.007, respectively), while stool frequency and sense of complete evacuation significantly improved only in the probiotic group (P < 0.05). Conclusions: This study demonstrated that multi-strain probiotics could improve frequency, consistency, and sense of complete evacuation in PD patients, while there was no significant effect on motor functions in 8 weeks. It is suggested that additional studies be conducted on longer-term effects.

Evaluating the effectiveness of probiotics in relieving constipation in Parkinson's disease: A systematic review and meta-analysis.

Objectives: The aim of this study was to evaluate the effects of probiotics on the treatment of constipation in patients with Parkinson's disease (PD) by analyzing data from published randomized clinical trials (RCTs). PD is a neurodegenerative disease characterized by clinical symptoms such as rigidity, bradykinesia, and resting tremor. Constipation is a common complaint reported by PD patients. Probiotics are often used to treat functional constipation. The potential mechanisms behind PD-related constipation include dysfunction of the enteric nervous system due to alpha-synuclein aggregation, dyssynergic contractions of the puborectalis muscle, and alterations of the gut microbiome. Method: To conduct this study, we searched Scopus, PubMed, and Google Scholar for published articles on PD, probiotics, and constipation. We selected RCTs from 944 studies, and ultimately included 3 RCTs in our meta-analysis. The frequency of bowel movements per week was the only index that could be summarized among the records. We extracted and analyzed the results as means and standard deviations. Result: We calculated a standardized mean difference (SMD) of 0.92 (95% CI, 0.65 to 1.19; I-squared = 57.0%; p < 0.001) to determine the treatment effect in terms of frequency of bowel movements per week in the RCTs. Conclusion: Our results show that probiotic intake has beneficial effects on constipation in PD patients. Further research, including multicenter studies, is needed to assess the long-term efficacy and safety of probiotic supplements in neurodegenerative diseases.

Recurrent middle cerebral artery stroke caused by arterial thoracic outlet syndrome and coagulopathy.

Thoracic outlet syndrome (TOS) is defined as compression of neurovascular components passing the thoracic outlet. While neurologic compression is the most common form, rare cases of arterial comprssion could result in concerning cerebral thromboembolic events. Here we present a 15-year-old female with repeated left hemiparesis and radiologic signs of cerebrovascular accident (CVA) in right middle cerebral artery. Further investigations revealed stenosis of the right subclavian artery, saccular aneurysm, and occlusion of the right brachial artery which suggested the diagnosis of arterial TOS. Based on this report, we present this diagnosis as a rare but important cause of CVA, especially in young patients.

Evaluation of neurosonology versus digital subtraction angiography in acute stroke patients.

Stroke is one of the most common neurological disorders with a high incidence in Middle-eastern regions. We aimed to assess the diagnostic accuracy of neurovascular ultrasound to detect of cerebral artery stenosis compared to digital subtraction angiography (DSA) as a gold standard method. Eighty patients presenting with symptoms of cerebral ischemia were enrolled in the study. They were examined by cervical color Doppler ultrasound and TCCS to determine stenosis of extracranial and intracranial arteries, respectively. DSA was performed 24-48 h after the initial examination. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of neurovascular ultrasound in comparison to DSA were calculated. The agreement between the two methods was determined by kappa statistics. Eighty patients (60% male, 40% female) with a mean age of 61.32 ± 12.6 years were included. In 65% of patients, stenosis in carotid artery caused ischemic symptoms. We did not observe any stenosis in anterior cerebral artery, posterior cerebral artery and basilar artery in patients. The agreement between the neurovascular ultrasound and DSA in various arterial vessels was 0.9 for common carotid artery, 0.86 for internal carotid artery, 0.78 for middle cerebral artery, and 0.86 for vertebral artery. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa value of the neurovascular ultrasound for detecting stenosis regarding the arterial segments were 84.8%, 81%, 92.6%, 65.4%, 83.8, and 0.71, respectively. In conclusion, the neurovascular ultrasound is a valuable, non-invasive, and repeatable method to investigate cerebral artery stenosis with high diagnostic accuracy.

Central nervous system manifestations in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: At the end of December 2019, a novel respiratory infection, initially reported in China, known as COVID-19 initially reported in China, and later known as COVID-19, led to a global pandemic. Despite many studies reporting respiratory infections as the primary manifestations of this illness, an increasing number of investigations have focused on the central nervous system (CNS) manifestations in COVID-19. In this study, we aimed to evaluate the CNS presentations in COVID-19 patients in an attempt to identify the common CNS features and provide a better overview to tackle this new pandemic. METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Ovid, EMBASE, Scopus, and Google Scholar. Included studies were publications that reported the CNS features between 1 January 2020 and 20 April 2020. The data of selected studies were screened and extracted independently by four reviewers. Extracted data analyzed by using STATA statistical software. The study protocol registered with PROSPERO (CRD42020184456). RESULTS: Of 2,353 retrieved studies, we selected 64 studies with 11,687 patients after screening. Most of the studies were conducted in China (58 studies). The most common CNS symptom of COVID-19 was headache (8.69%, 95%CI: 6.76%-10.82%), dizziness (5.94%, 95%CI: 3.66%-8.22%), and impaired consciousness (1.90%, 95%CI: 1.0%-2.79%). CONCLUSIONS: The growing number of studies has reported COVID-19, CNS presentations as remarkable manifestations that happen. Hence, understanding the CNS characteristics of COVID-19 can help us for better diagnosis and ultimately prevention of worse outcomes.

Neurological features and outcome in COVID-19: dementia can predict severe disease.

The COVID-19 pandemic has infected more than 22 million people worldwide. Although much has been learned about COVID-19, we do not know much about its neurological features and their outcome. This observational study was conducted on the patients of Imam Hossein Hospital, and 361 adult patients (214 males) with confirmed diagnosis of COVID-19 from March 5, 2020 to April 3, 2020, were enrolled. Data was gathered on age, sex, comorbidities, initial symptoms, symptoms during the disease course, neurological symptoms, and outcome. The mean age of the patients was 61.90 ± 16.76 years. The most common initial symptoms were cough, fever, and dyspnea. In 21 patients (5.8%), the initial symptom was neurological. History of dementia was associated with severe COVID-19 disease (odds ratio = 1.28). During the course of the disease, 186 patients (51.52%) had at least one neurological symptom, the most common being headache (109 [30.2%]), followed by anosmia/ageusia (69, [19.1%]), and dizziness (54, [15%]). Also, 31 patients had neurological complications (8.58%). Anosmia, ageusia, dizziness, and headache were associated with favorable outcome (P < 0.001), while altered mental status and hemiparesis were associated with poor outcome. The mortality rate of patients who had neurological complications was more than twice than that of patients without neurological complication (P = 0.008). Almost half of the patients experienced at least one neurological symptom, which may be the initial presentation of COVID-19. Dementia appears to be associated with severe COVID-19. Mortality was higher in patients with neurological complications, and these patients needed more intensive care.

Prevalence of sleep disorders in patients with epilepsy: A questionnaire-based cross-sectional study.

BACKGROUND: Sleep disturbance is a frequent finding in patients with epilepsy. As evaluation of sleep disorders and quality of sleep in patients with epilepsy may provide better management of these patients, we aimed to assess the prevalence of common sleep disorders in patients with epilepsy. METHODS: Patients with epilepsy referred to an outpatient epilepsy clinic in Tehran during one year were included. Validated Persian questionnaires were used by an interviewer to assess Excessive daytime sleepiness (EDS), Restless leg syndrome (RLS), and insomnia. Also, patients' demographic features and clinical seizure-related characteristics were recorded. RESULTS: Seventy patients (35 males) aged between 18 and 75 were enrolled. Among patients, 61.4, 35.7, and 28.6% suffered from insomnia, EDS, and RLS, respectively (mild to severe). When considering seizure characteristics, there was no significant correlation between either seizure frequency or its type and the prevalence of sleep disturbance (although sleep disturbance was more common among patients with higher seizure frequency and patients with generalized seizure). Interestingly, age had a positive correlation with EDS. CONCLUSION: This study showed that sleep disturbance is a common finding in patients with epilepsy, which may become severe in some cases. Taking this into consideration, we suggest that routine evaluation of sleep disorders may help physicians to boost patients' sleep quality.

COVID-19 Respiratory Illness and Subsequent Cerebrovascular Events, the Initial Iranian Experience.

OBJECTIVES: COVID-19 disproportionately affects older adults and individuals with cardiovascular co-morbidities. This report presents fifteen patients who had COVID-19 respiratory illness followed by cerebrovascular events. MATERIALS AND METHODS: A call by the Iranian Neurological Association gathered cases across the country who developed neurological symptoms attributed to hemorrhagic or ischemic stroke after a definite or probable Covid-19 respiratory illness. Definite cases were those with a typical respiratory illness, positive nasopharyngeal Covid-19 PCR test, and chest CT consistent with Covid-19 infection. Probable cases were defined by a typical respiratory illness, history of contacts with a Covid-19 case, and chest CT characteristic for Covid-19 infection. RESULTS: Fifteen patients (12 men and 3 women) with an age range of 38 to 93 years old (median: 65 years old) were included. Fourteen patients had a first-ever acute ischemic stroke and one patient had a subarachnoid hemorrhage. Eleven patients (73%) had previous cardiovascular comorbidities. The median time between respiratory symptoms and neurological symptoms was seven days (range 1-16 days). Stroke severity in two patients was mild (NIHSS ≤ 6), in six patients moderate (NIHSS: 7-12), and in seven patients severe (NIHSS ≥13). One patient received intravenous tissue plasminogen activator ( IV-tPA) with improved neurological symptoms. Six out of 15 patients (40%) died. All but one of those who survived had significant disability assessed by a modified ranking scale >2. The majority of patients in this case series had vascular risk factors and their stroke was associated with severe disability and death. CONCLUSION: This report highlights the need for further investigation of the links between Covid-19 and cerebrovascular events.

TRAILR1 (rs20576) and GRIA3 (rs12557782) are not associated with interferon-ß response in multiple sclerosis patients.

Multiple sclerosis (MS) is an autoimmune-type inflammatory disorder in human central nervous system. Recombinant interferon beta (IFN-ß) decreases the number of relapses and postpones disability progression in MS. However, up to 50% of patients treated with interferon beta continue experiencing relapses and/or worsening disability. Single nucleotide polymorphisms in different genes have been known to show significant associations with response to IFN-ß in MS patients. In the present work, we examined the potential role of TRAILR1 and GRIA3 genes polymorphisms on response to IFN-ß therapy in Iranian MS patients. The DNA was extracted from blood samples by standard procedures from 73 patients diagnosed with Multiple Sclerosis that were either responded to IFN-ß or did not. We carried out RFLP -PCR and tetra-primer ARMS-PCR methods to study of rs20576 and rs12557782, respectively. All results were analyzed using the SPSS software. TRAILR1 rs20576 genotype frequencies in responders and non-responders were similar (χ2 = 0.26, P = 0.87, Fisher, s Exact test). Our results showed that response to IFN-ß has not association with sex (p = 0.73). Also, genotypic frequencies of GRIA3 rs12557782 had no significant differences between two groups of female population (χ2 = 3.75, p = 0.15). Furthermore, it had not been any statistical differences between responder and non-responder males (χ2 = 0.7, p = 0.4) related to the SNP. Our results analysis revealed no significant association between the studied SNPs (TRAILR1 rs20576 and GRIA3rs 12,557,782) and response to IFN-ß in Iranian MS patients.

The Role of Mindfulness in Predicting Pain Interference in Patients with Primary Headache.

BACKGROUND: Primary headaches are one of the most troubled chronic diseases. Headaches interfere within the various dimensions of the patient's life. Coping strategies that aim to be attention focused (e.g., mindfulness) may moderate pain-related emotional and physical interference. OBJECTIVES: This investigation examined the relationship between mindfulness and pain intensity with physical and emotional interference and the subsequent aim was to analyze the role of mindfulness and headache severity combination in the prediction of pain-related interference. METHODS: This correlational study was conducted during years 2017 to 2018 at Imam Hossein Hospital of Tehran province. Eighty-five patients (56 females and 29 males), who had one type of primary headache were selected through purposive sampling after the diagnosis by a neurologist. The data were collected through the brief pain inventory (BPI) and the mindful attention awareness scale (MAAS). All data were analyzed using descriptive statistics. Bivariate correlation matrix and hierarchical stepwise linear regression statistics were used. RESULTS: The correlational analysis of the results indicated significant association between mindfulness (MAAS) and pain severity (BPI) (P < 0.01) as well as the findings of the study point to the significant relationship between mindfulness and both physical and emotional pain-related interference (P < 0.01). The results of stepwise linear regression indicated that pain severity explains only 1% of the total score in emotional pain-related interference (P = 0.003 and ΔF (1 and 83) = 9.22, ΔR2 = 0.11). Adding mindfulness to the model led to a 43% increase of the explained variance (R2 Change = 0.34). In physical interference, although pain severity was able to predict pain interference (P = 0.01 and ΔF (1 and 83) = 7.09, ΔR2 = 0.07), a combination model justifies 10% of the interference variance that was not statistically meaningful (P = 0.08, ΔR2 = 0.103). CONCLUSIONS: This result is a further support that Mindful Awareness contributed to emotional pain-related interference prediction. This result can explain the role of attention focused and mindful awareness in primary headache pain adjustment.

Frequency of dyslipidemia in migraineurs in comparison to control group.

BACKGROUND: Migraine is a common disease with neurovascular nature, which is commonly prevalent in the general population. Due to the significant prevalence of migraine and its long-term complications, it is necessary to pay attention to its exacerbating factors. Therefore, the aim of this study was to evaluate the frequency distribution of dyslipidemia in patients with migraine compared with control group. MATERIALS AND METHODS: This is a case-control study, in which 50 patients with migraine (with aura and without aura) were confirmed by the criteria of International Headache Society. Migraineurs and control group (n = 50) were selected from among patients who referred to the Neurology Clinic of Imam Hossein Hospital. The levels of total cholesterol, triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were measured in both the groups. SPSS software (version 21) was used to analyze the data. RESULTS: The findings showed that among migraineurs, 21 patients (42%) revealed high levels of cholesterol and 22 revealed high levels of LDL (44%); whereas among subjects without migraine, 12 subjects (24%) exhibited high levels of cholesterol and 12 (24%) high levels of LDL, where a significant correlation between the two groups was achieved. CONCLUSION: The present results showed that migraine is associated with higher level of cholesterol and LDL when compared with the control group, where a significant relationship was found.

Protective properties of the aqueous extract of saffron (Crocus sativus L.) in ischemic stroke, randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Crocus sativus L. has been used throughout the world in traditional medicine as a treatment for neurological disorders such as depression. Growing attention is currently being paid to the use of neuroprotective agents in ischemic strokes. AIM OF THE STUDY: This study assed the effect of saffron as a neuroprotective natural product in cerebral ischemia in human. STUDY DESIGN: Patients with acute ischemic stroke were randomly allocated to receive either routine stroke care (control group, n = 20) or routine care plus aqueous extract of saffron capsule (200 mg/day) (saffron-treated group, n = 19). Both groups were monitored during their four-day hospital stay and the three-month follow-up period. The groups were compared in terms of short- and long-term effects of saffron capsules using the National Institute of Health Stoke Scale (NIHSS), Barthel Scale, and serum neuron specific enolase (NSE), Brain-derived neurotrophic factor (BDNF), S100 levels. RESULTS: Based on the NIHSS, the severity of stroke during the first four days was significantly lower in the saffron-treated group than in the control group (P < 0.05). Compared to the levels on the first day, serum NSE and s100 levels were significantly decreased and BDNF concentration was increased in the saffron-treated group on the fourth day. Also, our results showed there was a negative significant non-linear cubic regression between BDNF concentration and score of NIHSS. At the end of the three-month follow-up period, the mean Barthel index was significantly higher in the saffron-treated group than in the control group (P < 0.001). CONCLUSION: The results of this study confirmed the short and long-term neuroprotective effects of aqueous extract of saffron on ischemic stroke in humans.

Use of Mindfulness-based Cognitive Therapy to Change Pain-related Cognitive Processing in Patients with Primary Headache: A Randomized Trial with Attention Placebo Control Group.

BACKGROUND: Mindfulness-based interventions have shown to be efficient in managing chronic pain. Cognitive factors play a prominent role in chronic pain complications and negative cognitive contents about pain are often the first issues targeted in cognitive-based therapies, which are known as first-line treatment of chronic pain over the past decades. Little, however, is known about the manner of thinking about pain or pain-related cognitive processing. OBJECTIVES: Therefore, the purpose of this study was to investigate the effect of mindfulness-based cognitive therapy (MBCT) on pain-related cognitive processing and control of chronic pain in patients with primary headache. METHODS: A clinical trial was conducted in 2017 - 2018 on 85 Persian language patients with one type of primary headache selected through purposive sampling in Emam Hossein Hospital in Tehran province. To measure the variables of the study, we used the Brief Pain Inventory (BPI) and Pain-related Cognitive Processing Questionnaire (PCPQ). All data were analyzed by independent t-test and chi-square and longitudinal data were analyzed using linear mixed model analysis. RESULTS: Statistically significant time × group interactions were found in pain intensity (P < 0.001), pain interference (P < 0.001), as well as in three cognitive processing subscales including pain focus, pain distancing, and pain openness (P < 0.001). However, the results of pain diversion were not meaningful. CONCLUSIONS: MBCT is a potentially efficacious approach for individuals with headache pain. Regulation and correction of cognitive processing are considered as effective cognitive coping strategies in MBCT treatment.

Comparison of Pregabalin and Sodium Valproate in Migraine Prophylaxis: A Randomized Double-Blinded Study.

Patients suffering from headache, particularly migraine type, are among the most dissatisfied patients. The aim of this study was comparing the efficacy of pregabalin with valproate sodium, in preventing migraine headache. In a randomized, double-blinded study, adult patients eligible for prophylactic treatment (i.e., patients with 4-15 attacks per month in last two months) were recruited. Patients' demographic data, duration of symptoms, headache frequency (attacks per month) and intensity (based on visual analogue scale) and also drugs used to relief headache were recorded. The patients were randomly assigned to two groups; valproate sodium (200 mg two times daily) and pregabalin (50 mg two times daily). The patients were examined by neurology specialist monthly for three months and the related data were recorded. The Data were analyzed using SPSS version 21, with related statistical tests. Total number of 140 patients with recurrent migraine were entered into the study. Sixty-nine patients were assigned to group A and 71 to group B by the randomizing table. Inter-group analysis of data in two arms of the study showed that two medications were equally effective except that pregabalin was not significantly effective in reducing number of attacks during first month of therapy compared to baseline. This differences were not significant at second and third month of the study. Our study showed that pregabalin, has comparable efficacy with valproate sodium in reducing migraine frequency, intensity, and duration of attacks and could be an alternative for migraine prophylaxis.

Vitamin B12 Deficiency as a Cause of Neurotrophic Keratopathy.

INTRODUCTION: Neurotrophic keratitis is a rare degenerative corneal disease caused by an impairment of trigeminal corneal innervation, leading to a decrease or absence of corneal sensation. Here, we present a case of neurotrophic keratopathy caused by B12 deficiency in a 34 years old man who had a progressive decrease in visual acuity and corneal involvement since 3 months before being referred to our ophthalmology clinic. RESULT AND DISCUSSION: Based on our clinical findings and with the diagnosis of B12 deficiency we started B12 treatment for the patient. After 3 weeks the patient showed a dramatic response with corneal sensation reversal, an increase of visual acuity, improved neurotrophic keratopathy and significantly improved neurological findings. To the best of our knowledge, there is no report regarding vitamin B12 deficiency induced keratopathy and this is the first report that describes this aspect of vitamin B12 deficiency.

Cognitive Processing Styles and Mindfulness on Pain Intensity Prediction in People with Primary Headache.

BACKGROUND: Primary headaches are the most common cause of absence from work and school and one of the most common reasons for referring to the neurologists. OBJECTIVES: The present study was designed to investigate the relationship of cognitive processing style and mindfulness with pain intensity and the ultimate aim was to provide the role of pain-related cognitive processes and mindfulness in the prediction of headache intensity. METHODS: The study was conducted descriptively by using the correlation method. The statistical population of this study was composed of 85 patients (56 females and 29 males) with one type of primary headache, which were selected through purposive sampling after the diagnosis of a headache by a neurologist at Imam Hossein Hospital in Tehran province. To measure the variables of the study, the numeric pain rating scale (NRS) and the pain-related cognitive processes questionnaire (PCPQ) were used. All data were analyzed using descriptive statistics (frequency and percentages). Bivariate correlation matrix and hierarchical stepwise linear regression statistics were used. RESULTS: The results showed that there was a significant and negative association between pain intensity (NRS) and mindfulness (P < 0.01) and all pain-related cognitive processes, except pain focus (P < 0.01). The results of stepwise linear regression indicated that mindfulness only explains 39% of total score changes in pain intensity (P < 0.05 and ΔF (1 and 83) = 53.63, ΔR = 0.385). Adding cognitive processing styles to the model led to an 18% increase of the explained variance (R2 change = 0.179). In total, the present research model justifies 54% of the severity of headache variance (P < 0.01, ΔR = 0.54). CONCLUSIONS: The results suggest that pain-related cognitive processes and mindfulness are effective on pain intensity prediction. In other words, this result can explain the role of mindfulness and adaptive cognitive processing in primary headache pain management.

Tolerability and Efficacy of Memantine as Add on Therapy in Patients with Migraine.

Prophylactic migraine treatment has always been a challenge. Efficacy and tolerability are two main issues in current approved migraine prevention regimens. Since some migraine patients fail approved preventative agents, experts are always seeking newer agents. Memantine, a glutaminergic antagonist, could potentially be one of these agents. Objective of current study is assessing the efficacy of memantine as a preventative migraine treatment and its potential side effects. In this study, 127 migraine patients meeting the criteria for starting preventative therapy (> 4 headache days/month) are included in the study. All patients were previously failed in at least one trial of adequate preventive therapy. After a 30 day baseline observation, patients started memantine for 3 months, beginning at 5 mg/day, which increased by 5 mg/week up to a maximum of 20 mg a day if symptoms did not improve. Headache frequency, duration, and severity were assessed at the end of the treatment phase. 102 patients completed the study. In the study population, headache frequency reduced from 9.9 days/month at baseline to 5 days/month at 3 months (P < .001). The mean severe pain reduced from 6.9 to 3.6 at 3 months (P < .001). Headache duration significantly reduced at 3 months, compared with baseline (P < .001). Side effects related to memantine consumption were uncommon and generally mild. Based on preliminary data, there is some evidence that memantine might be useful in the treatment of refractory migraine. This is in line with previous pilot and open label studies. However, double blind studies are still needed.

Acute management of stroke in Iran: Obstacles and solutions.

Background: Stroke is among the leading causes of mortality and permanent disability in the world. Iran is located in the stroke belt and has a high age-adjusted stroke incidence rate. In this multistep prospective qualitative study, we aimed at investigating the status and challenges of stroke management in Iran and explore possible solutions. Methods: In the first and second phase, we attempted to define the status of stroke management in Iran by searching the relevant literature and conducting semi-structured interviews with health-care providers in thirteen hospitals located in seven large cities in Iran. In the third phase, we tried to recommend possible solutions based on international standards and experience, as well as interviews with stroke experts in Iran and the United States. Results: Little public awareness of stroke symptoms and its urgency, low prioritization for stroke management, and an inadequate number of stroke-ready hospitals are some of the major obstacles toward timely treatment of stroke in Iran. Every hospital in our pool except two hospitals had guideline-based algorithms for the administration of intravenous thrombolysis. However, there was no single call activation system for stroke alert. Data from some of the centers showed that hospital arrival of stroke patients to final decision-making took 116-160 minutes. Although there were four endovascular programs in our target areas, there was no center with 24-hour coverage. Conclusion: There are many challenges as well as potentials for improvement of stroke care in Iran. Improving public knowledge of stroke and establishing an organized and comprehensive stroke program in the hospitals will improve acute stroke management in Iran. The Iranian ministry of health should define and advocate the establishment of stroke centers, track the rate of death and disability from stroke, introduce pathways to improve the quality of stroke care through national data monitoring systems, and eliminate disparities in stroke care.

Efficacy and Safety of MLC601 in the Treatment of Mild Cognitive Impairment: A Pilot, Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND AND AIM: Mild cognitive impairment (MCI) is characterized by declined cognitive function greater than that expected for a person's age. The clinical significance of this condition is its possible progression to dementia. MLC601 is a natural neuroprotective medication that has shown promising effects in Alzheimer disease. Accordingly, we conducted this randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of MLC601 in MCI patients. METHODS: Seventy-two patients with a diagnosis of MCI were recruited. The included participants were randomly assigned to groups to receive either MLC601 or placebo. An evaluation of global cognitive function was performed at baseline as well as at 3-month and 6-month follow-up visits. Global cognitive function was assessed by Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores. Efficacy was evaluated by comparing global function scores between the 2 groups during the study period. Safety assessment included adverse events (AEs) and abnormal laboratory results. RESULTS: Seventy patients completed the study, 34 in the MLC601 group and 36 in the placebo group. The mean changes (±SD) in cognition scores over 6 months in the MLC601 group were -2.26 (±3.42) for the MMSE and 3.82 (±6.16) for the ADAS-cog; in the placebo group, they were -2.66 (±3.43) for the MMSE and 4.41 (±6.66) for the ADAS-cog. The cognition changes based on both MMSE and ADAS-cog scores were statistically significant between the placebo and the MLC601 group (p < 0.001). Only 5 patients (14.7%) reported minor AEs in the MLC601 group, the most commonly reported of which were gastrointestinal, none of them leading to patient withdrawal. CONCLUSION: MLC601 has shown promising efficacy and acceptable AEs in MCI patients.

The buffering effect of family functioning on the psychological consequences of headache.

The current study aimed to examine whether high family functioning mitigates the association between headache intensity and distress. The sample consisted of 124 patients with chronic or recurrent headache. Patients completed validated questionnaires about headache intensity, family functioning, and distress. Hierarchical regression analyses were performed to examine the interaction between headache intensity and family functioning on distress. Headache intensity was positively associated with distress (r = .28, p = .002). As hypothesized, family functioning moderated this association (B = -.01, p = .023). More specifically, the positive association between headache intensity and distress was significant only among patients with lower family functioning (B = .01, p < .001) and not among patients with higher levels of family functioning (B = .006, p = .075). Functional families appear to buffer the distress level in patients; they showed relatively low levels of distress regardless of the severity of their headache. In contrast, patients with dysfunctional families who experienced more pain reported more distress, presumably because they did not receive adequate help and support from these families. This study underlines the importance of a broader perspective on family dynamics in coping with pain.