The role of microRNAs in neurobiology and pathophysiology of the hippocampus.

MicroRNAs (miRNAs) are short non-coding and well-conserved RNAs that are linked to many aspects of development and disorders. MicroRNAs control the expression of genes related to different biological processes and play a prominent role in the harmonious expression of many genes. During neural development of the central nervous system, miRNAs are regulated in time and space. In the mature brain, the dynamic expression of miRNAs continues, highlighting their functional importance in neurons. The hippocampus, as one of the crucial brain structures, is a key component of major functional connections in brain. Gene expression abnormalities in the hippocampus lead to disturbance in neurogenesis, neural maturation and synaptic formation. These disturbances are at the root of several neurological disorders and behavioral deficits, including Alzheimer's disease, epilepsy and schizophrenia. There is strong evidence that abnormalities in miRNAs are contributed in neurodegenerative mechanisms in the hippocampus through imbalanced activity of ion channels, neuronal excitability, synaptic plasticity and neuronal apoptosis. Some miRNAs affect oxidative stress, inflammation, neural differentiation, migration and neurogenesis in the hippocampus. Furthermore, major signaling cascades in neurodegeneration, such as NF-Kß signaling, PI3/Akt signaling and Notch pathway, are closely modulated by miRNAs. These observations, suggest that microRNAs are significant regulators in the complicated network of gene regulation in the hippocampus. In the current review, we focus on the miRNA functional role in the progression of normal development and neurogenesis of the hippocampus. We also consider how miRNAs in the hippocampus are crucial for gene expression mechanisms in pathophysiological pathways.

The Efficacy and Safety of Intrathecal Autologous Bone Marrow-Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis: A Pilot Study.

Purpose: Amyotrophic lateral sclerosis (ALS) is an uncommon and aggressive neurodegenerative disorder that influences the lower and upper motor neurons. There are low eligible drugs for ALS treatment; in this regard, supplemental and replacement treatments are essential. There are relative studies in the field of mesenchymal stromal cells (MSCs) therapy in ALS, but the different methods, differently used medium, and difference in follow-up periods affect the outcome treatment. Methods: The current survey is a single-center, phase I clinical trial to evaluating the efficacy and safety of autologous bone marrow (BM)-derived MSCs through intrathecal administration in ALS patients. MNCs were isolated from BM specimens and cultured. The clinical outcome was evaluated based Revised Amyotrophic Lateral Sclerosis Functional Rating (ALSFRS-R) Scale. Results: Each patient received 15±3×106 cells through subarachnoid space. No adverse events (AEs) were detected. Just one patient experienced a mild headache after injection. Following injection, no new intradural cerebrospinal pathology transplant-related was observed. None of the patients' pathologic disruptions following transplantation were detected by magnetic resonance imaging (MRI). The additional analyses have shown the average rate of ALSFRS-R score and forced vital capacity (FVC) reduction have decreased during 10 months following MSCs transplantation versus the pretreatment period, from -5.4±2.3 to -2±3.08 ALSFRS-R points/period (P=0.014) and -12.6±5.22% to -4.8±14.72%/period (P<0.001), respectively. Conclusion: These results have shown that autologous MSCs transplantation reduces the disease's progression and has favorable safety. Trial Registration: This study performed as a phase I clinical trial (code IRCT20200828048551N1).

Outcome predictors in anterior and posterior ischemic strokes: a study based on the Iranian SITS registry.

Ischemic stroke is the major form of stroke with two separate vascular territories. Many risk factors are related to stroke outcomes in both territories. The present descriptive research was carried out on the basis of data obtained from the Safe Implementation of Treatments in Stroke (SITS) registry on Iranian intravenous thrombolysis ischemic stroke cases. Vascular territory involved in each case and three-month excellent outcome, functional independence, mortality rate, and brain hemorrhage occurrence were determined. Univariable and multivariable logistics regression analyses were utilized in order to investigate association of ischemic stroke outcomes with the vascular territory involved and other related factors. Among 1566 patients 95.4% was anterior circulation stroke patients and 4.6% was posterior circulation stroke cases. There is no significant association between vascular territory with mortality (OR of PCS vs ACS: 0.74, 95% CI 0.37-1.46), excellent functional outcome (OR 0.72, 95% CI 0.44-1.19), functional outcome (OR 0.86, 95% CI 0.52-1.42) and local hemorrhage (OR 0.98, 95% CI 0.30-3.21). Among major risk factors, age, diabetes, NIHSS score and admission duration, increased significantly odds of three-month mortality, excellent outcome, and functional independence in the multivariate analysis. The highest of odds was in NIHSS score with a dose-response association. The vascular territory was not an outcome predictor in ischemic strokes. The most important predictor was baseline NIHSS.

A comparative study on the effectiveness of topiramate and propranolol in patients with migraine with aura.

Background: Migraine is considered as one of the most common and disabling diseases of the nervous system that has a great impact on quality of life (QOL) and a little risk of neurologic complications such as stroke. Migraine aura is known to be the result of cortical spreading depression and is associated with higher risk of this complication. Thus, the present study was conducted with the aim to compare the effects of topiramate as an antiepileptic, and propranolol in patients with migraine with aura. Methods: The present randomized clinical trial was conducted on patients with migraine with aura referred to the neurology clinic of Golestan Hospital, Ahvaz, Iran, in the period of 2019-2020. The patients were randomized into two groups and received either topiramate or propranolol. The Migraine Disability Assessment Scale (MIDAS) score was evaluated before and at the end of three months after initiating the treatment. Results: Reduction in the MIDAS score in patients taking topiramate (-16.94) was greater than that in the propranolol group (-14.5), but this difference was not statistically significant (P > 0.005). No significant relationship was found between gender and changes in the MIDAS score after the treatment of both groups (P > 0.050). However, the changes in the MIDAS score were greater in younger patients, and this relationship was statistically significant (P < 0.050). Conclusion: There was no significant difference in the efficacy of topiramate and propranolol in patients with migraine with aura. No significant relationship was found between gender and changes in the MIDAS score after the treatment in both groups, but the reduction in the MIDAS scores was significantly higher in younger patients of both groups.

The effect of prehospital notification by emergency medical service on outcomes in patients receiving recombinant tissue-type plasminogen activator (r-tPA).

Background: According to the American Heart Association and American Stroke Association (AHA/ASA) guidelines, in acute stroke, the door-to-computed tomography (CT) scan (DTC) time should be less than 25 minutes, and time to injection of recombinant tissue-type plasminogen activator (r-tPA) [door-to-needle (DTN) time] should be less than 60 minutes. Methods: We had a tendency to prospectively collect the clinical and time information of patients who received r-tPA during one year after the initiation of prehospital notification (PN). Patients were divided into three groups, covering patients transferred by Emergency Medical Service (EMS) with and without PN, and non-EMS. We then contrasted the impact of EMS with PN and EMS use on onset-to-needle time (ONT), and the neurological outcome. Good outcome was determined as Modified Rankin Scale (MRS) ≤ 2 at 3-month follow-up. Results: Among 102 studied patients, 64% were transferred by EMS, of whom 53.9% entered PN. Compared with non-PN groups, EMS with PN group showed significantly shorter DTN and DTC time, as well as ONT. Conclusion: Our study showed that EMS with PN, rather than EMS, significantly improved stroke outcome by shortening of ONT.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Low-dose versus standard-dose alteplase for intravenous thrombolysis in patients with acute ischemic stroke in Iran: Results from the safe implementation of treatments in stroke registry.

Background: Rates of intracranial hemorrhage (ICH) after intravenous thrombolysis (IVT) differ depending on ethnicity, one reason that few Eastern countries have approved a lower dose of alteplase. Data in this regard are scarce in the Middle Eastern region. Methods: The present retrospective study was performed on data extracted from the Safe Implementation of Treatments in Stroke (SITS) registry. Computed tomography (CT) image analysis was based on the SITS-Monitoring Study (SITS-MOST) definition for symptomatic ICH (SICH). Functional outcome at 3 months was assessed using the modified Rankin Scale (mRS). Multivariate logistic regression including adjusted analysis was used for comparison between groups. Results: Of 6615 patients, 1055 were enrolled. A total of 86% (n = 906) received a standard dose and 14% (n = 149) received a low dose of alteplase. Favorable 3-month outcome was achieved in 481 (53%) patients in the standard group and 71 (48%) patients in the low-dose group [adjusted odds ratio (AOR) = 1.24, 95% confidence interval (CI): 0.87-1.75, P = 0.218]. SICH occurred in 14 (1.5%) patients in the standard group and 3 (2%) patients in the low-dose group [odds ratio (OR) = 2.77, 95% CI: 0.36-21.04, P = 0.120]. At 3 months, mortality occurred in 145 (16.0%) patients in the standard group and 29 (19.4%) patients in the low-dose group (OR = 1.22, 95% CI: 0.78-1.91, P = 0.346). Conclusion: Low-dose compared to standard-dose alteplase for patients with acute ischemic stroke (AIS) was not associated with fewer hemorrhagic events and there was no significant difference in the favorable 3-month outcome (mRS: 0-2) or mortality rate.

Relationship between functional balance and walking ability in individuals with chronic stroke.

[Purpose] The objective of this cross sectional study was to investigate the validity of Functional Ambulation Category in evaluating functional balance and identifying the relationship between balance impairment and functional ambulation in individuals with chronic stroke. [Participants and Methods] A total of 31 chronic stroke patients with first ever ischemic middle cerebral artery strokes, with no cognitive deficits were recruited. Participants had a mean age of 54.84 (SD=7.05) years and a time after stroke of 22.74 (SD=27.13) months. Community ambulation was determined by Functional Ambulation Category and functional balance was assessed by Berg Balance Scale. [Results] The mean Berg Balance Scale and the Functional Ambulation Category scores were 47.38 (SD=7.54) and 3.8 (SD=0.79), respectively. Correlation analysis revealed that balance impairment and ambulatory function was significantly positively correlated with each other (r=0.80). [Conclusion] The results shows that the Functional Ambulation Category is a valid tool in evaluating functional balance and suggest that functional balance may be an important goal for rehabilitation to achieve improvement in walking ability in people with chronic stroke.

Botulism Outbreak in a Family after Ingestion of Locally Produced Cheese.

Botulism is one of the most important foodborne diseases and is caused by Clostridium botulinum toxin. The main manifestations are flaccid muscle paralysis and cranial nerve palsies. Botulism is an essential health problem because of its high mortality. The diagnosis of botulism, especially in sporadic cases, is a medical challenge and a high clinical suspicion is necessary for early recognition. So, every physician should be familiar with its signs and symptoms for early detection and treatment. We describe a family with dysphasia and acute paralysis after the ingestion of locally made cheese. The clinical presentations of the 1st patient were similar to myasthenic crisis and she, therefore, received plasma exchange. After the appearance of similar symptoms in the other family members, they were treated with polyvalent botulinum antitoxin and diagnosis was confirmed by toxicology and detection of serotype A botulinum toxin in cheese and stool samples. Uncommon clinical presentations and unusual sources of botulinum toxin should be kept in mind because of the importance of early diagnosis and treatment.

Restless legs syndrome in hemodialysis patients.

Restless legs syndrome (RLS) is a neurological disorder characterized by uncomfortable sensation of paresthesia in legs that subsequently causes involuntary and continuous movement of the lower limbs, especially at rest. Its prevalence in hemodialysis is more than that in the general population. Different risk factors have been suggested for RLS. We studied the prevalence and risk factors of RLS in 137 hemodialysis patients followed up at our center. The patients completed at least three months on dialysis and fulfilled four criteria for the diagnosis of RLS. We compared the patients with and without RLS, and the odds ratios (ORs) were estimated by the logistic regression models. The prevalence of RLS was 36.5% in the study patients. Among the variables, diabetes was the only predicting factor for the development of RLS. The diabetic patients may be afflicted with RLS 2.25 times more than the non-diabetics. Women developed severe RLS 5.23 times more than men. Neurodegeneration, decrease in dopamine level, higher total oxidant status, and neuropathy in diabetic patients may explain the RLS symptoms.