Medication adherence, anxiety and depression, and safety of epileptic patients following receiving information about sudden unexpected deaths in epilepsy: A quasi-experimental study with before/after design.

INTRODUCTION: It is very important to provide epileptic patients with sufficient knowledge of SUDEP and empower them regarding its prevention. This study aimed to evaluate the effect of the educational intervention of receiving information about SUDEP on medication adherence, anxiety and depression, and the safety of epileptic patients. PATIENTS AND METHODS: This study was conducted on 60 epilepsy patients referred to the specialized epilepsy clinic of Imam Hossein Hospital in Tehran, Iran, from April 2022 to February 2023. Data were collected by the Morisky medication adherence scale, hospital anxiety and depression scales, and the researcher-made checklists of bathing safety, sleep safety, and patient seizure preparation before and after the intervention. The educational intervention was conducted through the video and pamphlet regarding knowledge about SUDEP. Wilcoxon and paired t-tests were used to compare the data changes following the intervention. RESULTS: Most patients were male, with an age range of 18 to 29 years old. The mean score of anxiety and depression before and after the educational intervention did not show a statistically significant difference (P = 0.928); however, the mean scores of medication adherence, bathing safety, sleep safety, and preparation for seizure after the educational intervention increased significantly (P < 0.05). CONCLUSION: Knowledge about SUDEP would be able to encourage epileptic patients to better adhere to medication; and make them empower regarding seizure preparation, bathing safety, and sleep safety.

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.

Carotid intima-media and epicardial adipose tissue thickness in adult patients with epilepsy taking anti-seizure medication and its long-term significance.

OBJECTIVES: We investigated epicardial adipose tissue thickness (EATT), carotid intima-media thickness (CIMT), and lipid profile in adult patients with epilepsy (PWE) taking anti-seizure medication(s) (ASM) and compared with those of the healthy population. We also investigated whether duration of follow-up and number of ASM(s) (mono- vs. polytherapy) affect these risk factors. METHODS: Twenty PWE older than 18 years of age were recruited at the outpatient epilepsy clinic and compared to twenty controls. Patients who were 18 years old and younger, those with cardiovascular risk factors, and patients with follow-up duration less than 2 years were excluded from the study. RESULTS: Epicardial adipose tissue thickness and CIMT were thicker compared to controls. While patients' low-density lipoprotein (LDL) levels were higher than controls, and high-density lipoprotein (HDL) levels were lower, the levels were in normal ranges. Those patients with duration of follow-up more than five years had thicker EATT. The 5-year LDL was in normal ranges while HDL was abnormally low. Number of ASM(s) was not associated with increased risks of atherosclerosis. Increased CIMT in patients taking ASM(s) was independent of their lipid profile. CONCLUSION: Anti-seizure medications contribute to accelerated atherosclerosis in people with epilepsy. Chronic use of ASMs may increase this chance. It is appropriate to use ASM(s) with lower chances of atherosclerosis in people with epilepsy and encourage them to change their lifestyle in order to modify cardiovascular risk factors. Meantime, it is reasonable to assess the risk of atherosclerosis periodically in these patients by noninvasive methods including lipid profile, CIMT, and EATT.

Ethical considerations in neurology during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) pandemic has struck many countries and caused a great number of infected cases and death. Healthcare system across all countries is dealing with the increasing medical, social, and legal issues caused by the COVID-19 pandemic, and the standards of care are being altered. Admittedly, neurology units have been influenced greatly since the first days, as aggressive policies adopted by many hospitals caused eventual shut down of numerous neurologic wards. Considering these drastic alterations, traditional ethical principles have to be integrated with state-of-the-art ethical considerations. This review will consider different ethical aspects of care in neurologic patients during COVID-19 and how this challenging situation has affected standards of care in these patients.

Neurological Complications of COVID-19: A Rare Case of Bilateral Blindness.

BACKGROUND: There are growing reports of the neurological involvement among patients with coronavirus disease 2019 (COVID-19). Headache, confusion, and anosmia after olfactory nerve disruption are the most prevalent presentation of the neurological involvement related to COVID-19. However, small numbers of the central nervous system involvement have been reported. CASE REPORT: A 49-year-old man was referred to our hospital with abrupt vision loss. Three weeks earlier he was admitted to the hospital based on his respiratory symptoms and was diagnosed with COVID-19 infection. Initial brain magnetic resonance imaging indicated diffuse restricted bilateral foci in both parietal and occipital lobes in favor of acute infarction. Diffuse weighted imaging demonstrated restricted bilateral hyperintense signals in parietal and occipital region. Occipital cortex biopsy showed brain tissue with focal infiltration of foamy macrophages mixed with reactive astrocytes and no plasma cell infiltration. Considering all of the evidence, post-COVID-19 encephalitis diagnosis was considered for the patient, and methyl prednisolone pulse therapy and intravenous immunoglobulin were initiated. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although there are growing reports of neurological involvement among patients, blindness is rarely observed as a complication of post-COVID-19 encephalitis. To our knowledge, this is the first case of post-COVID-19 encephalitis that presented with bilateral vision loss primarily. This case may raise physicians' awareness of neurological complications of COVID-19.

Pivotal cytokines and their transcription factors are the targets of guluronic acid (G2013) for inhibiting the immunopathogenesis process of multiple sclerosis.

The α-L-guluronic acid (G2013), is a novel immunosuppressive drug (PCT/EP2017/067920). One of the most popular ideas in designing drugs for multiple sclerosis (MS) is to restrict the main inflammation-related lymphocytes and cytokines. The foremost problems with conventional drugs are their side effects and low efficacy. In order to rectify these problems, we examined the effect of two doses of G2013 on the gene expression of IFN-γ, IL-17, IL-22, T-bet, RORC, and AHR, in MS patients PBMCs. RNA was extracted from peripheral blood mononuclear cell (PBMC) of 12 relapsing-remitting MS patients and 12 healthy volunteers and the effect of two doses of G2013 on the gene expression of IFN-γ, IL-17, IL-22, T-bet, RORC, and AHR, were assessed by real-time PCR. Overall, the results show that G2013 is able to significantly reduce the gene expression of IL-22, AHR, RORC, and T-bet. Collectively, G2013 might be considered and studied as a new drug of possible use to MS patients due to its immunosuppressive property on some of the main inflammatory cytokine and transcription factors.

Interesting Manifestation of Autoimmune Encephalitis on FDG PET Scan.

ABSTRACT: We are presenting a 22-year-old man with intractable seizures. Autoimmune epilepsy, vasculitis, and paraneoplastic disorder were among initial differential diagnoses. His initial laboratory tests and toxicology screen were unremarkable. His initial brain MRI demonstrated generalized cortical atrophy. Features such as progressive encephalopathy, neuropsychiatric symptoms, personality change, and autonomic dysfunction were in favor of autoimmune encephalitis. Autoantibody evaluations including anti-NMDA receptor (NR1) IgG were negative in both serum and CSF samples. FDG PET scan demonstrated intense FDG uptake in the basal ganglia, more prominent in the caudate nuclei and putamina, which is one of the known autoimmune encephalitis imaging features.

Severe acute respiratory syndrome coronavirus 2 and seizure: An insight into the pathophysiologic mechanisms.

Based on previous studies, seizure has been reported to accompany coronavirus disease 2019 (COVID-19). Underlying mechanisms are those leading to the direct central nervous system (CNS) invasion through hematogenous spread or trans-synaptic retrograde invasion, causing meningoencephalitis. On the other hand, there are pathophysiologic mechanisms that seizure would be one of their early consequences, such as cytokine storm, hypoxemia, metabolic derangement, and structural brain lesions. Herein, we focused on available evidence to provide an insight into the pathophysiologic mechanisms that link seizure and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as a better understanding of pathophysiology would lead to better diagnosis and treatment.

Potentially inappropriate brain CT-scan requesting in the emergency department: A retrospective study in patients with neurologic complaints.

BACKGROUND: Potentially inappropriate brain CT scan requesting in the emergency department imposes extra charges to the healthcare system and patients. Besides, the unnecessary radiation exposure may cause irreparable damage to the patient. In this study we investigated the percentage of potentially inappropriately conducted brain CT scan for different chief complaints in non-traumatic patients presented to our emergency department.  Material and methods: 160 patients aged over 18 years old with chief complaints other than trauma, referred to the emergency department of Imam Hossein Hospital (Tehran, Iran), were enrolled in this study. Data were collected from medical records; the inclusion criteria was patients older than 18 years with chief complaint other than trauma.  Results: 160 people aged 18 to 100 years old enrolled in this study, 83 (51.87%) were male and 77 (48.13%) were female. There was no statistically significant difference in terms of potentially inappropriate brain CT between different age groups. Percentage of potentially inappropriate CT according to chief complaints were as follows: 4.8% for dysarthria, 0% for right and left hemiplegia, 9.1% for decreased level of consciousness, 30% for nausea and vomiting, 41.7% for generalized weaknesses, 0% for seizures, 55.6% for vertigo, 25% for headache, and 57.7% for other complaints. There was a statistically significant association between chief complaints and potentially inappropriate brain CT scan requests (p-value = 0.001). CONCLUSION: Considering the significant percentage of potentially inappropriate brain CT scan requests for non-traumatic patients in the setting of emergency department, it is critical for healthcare policymakers to propose practical guidelines and supervise their application.

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.

Plasma Cytokines Profile in Subjects with Alzheimer's Disease: Interleukin 1 Alpha as a Candidate for Target Therapy.

Background: Alzheimer's disease (AD) is the main cause of the neurodegenerative disorder, which is not detected unless the cognitive deficits are manifested. An early prediagnostic specific biomarker preferably detectable in plasma and hence non-invasive is highly sought-after. Various hypotheses refer to AD, with amyloid-beta (Aß) being the most studied hypothesis and inflammation being the most recent theory wherein pro-and anti-inflammatory cytokines are the main culprits. Materials and Methods: In this study, the cognitive performance of AD patients (n=39) was assessed using mini-mental state examination (MMSE), AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating (CDR). Their neuropsychiatric symptoms were evaluated through neuropsychiatric inventory-questionnaire (NPI-Q). Moreover, plasma levels of routine biochemical markers, pro-/anti-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1 α (IL-1α), IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-12p70, IL-10, Interferon-gamma, chemokines, including prostaglandin E2 (PGE-2), monocyte chemoattractant protein-1, interferon gamma-induced protein 10, Aß peptide species (42, 40) and Transthyretin (TTR) were measured. Results: Our results revealed that Aß 42/40 ratio and TTR were correlated (r=0.367, P=0.037). IL-1α was directly correlated with ADAS-cog (r=0.386, P=0.017) and Aß 40 (r=0.379, P=0.019), but was inversely correlated with IL-4 (r=-0.406, P=0.011). Negative correlations were found between MMSE and PGE2 (r=-0.405, P=0.012) and TNF-α/ IL-10 ratio (r=-0.35, P=0.037). CDR was positively correlated with both PGE2 (r=0.358, P=0.027) and TNF-α (r=0.416, P=0.013). There was a positive correlation between NPI-caregiver distress with CDR (r=0.363, P=0.045) and ADAS-cog (r=0.449, P=0.019). Conclusion: Based on the observed correlation between IL-1α, as a clinical moiety, and ADAS-cog, as a clinical manifestation of AD, anti-IL-1α therapy in AD could be suggested.

The Effect of Intradermal Botulinum Toxin a injections on painful diabetic polyneuropathy.

BACKGROUND AND AIMS: Botulinum toxin type A (BTX-A) have been recently administered to improve Diabetic neuropathies; however, the efficacy of this treatment for relieving pain in painful diabetic polyneuropathy (DPN) has not been studied yet. Herein, we investigated the efficacy of botulinum toxin A (BTX-A) on DPN. METHODS: This prospective, randomized, double-blind, controlled trial was performed in Imam Hossein Medical Center, pain clinic (Tehran, Iran). Diabetic patients (141 cases), between 40 and 70 years old with polyneuropathy in lower limbs were randomly assigned to one of these three groups: 1. Group D1 received 150 units of BTX-A in one foot and normal saline 0.9% in the other foot, 2. Group D2 received BTX-A 150 units in both feet, 3. Group N received normal saline 0.9% in both feet. All injections were performed intradermally using insulin syringes in 20 different points of foot. Visual analogue scale (VAS) and neuropathy pain scale (NPS) were used to compare the groups. RESULTS: The improvement of VAS, pain intensity, sharp and hot sensation, sensitive and unpleasant sensation, deep and surface sensation was significant when comparing BTX-A and placebo groups. However, dull and cold sensations improvement (p = 0.114, and p = 0.653; respectively) did not show a significant difference between BTX-A injection and placebo groups. Furthermore, the percentage of changes after treatment indicated that sharp pain was improved more than other complaints (80%, 81%, and 37% for D1, D2, and N groups; respectively). CONCLUSION: Intradermal administration of BTX-A was effective in improving VAS and all of the items of NPS in patients with diabetic polyneuropathy, except for dull and cold sensation.

RAR-related orphan receptor A: One gene with multiple functions related to migraine.

AIMS: RAR-related orphan receptor (RORA) involves in regulation of several biological processes including inflammation and circadian rhythm that probably are involved in migraine pathophysiology. In the current study, the association between RORA rs11639084 and rs4774388 variants and susceptibility to migraine were investigated in a sample of Iranian migraine patients for the first time. METHODS: In a case-control study including 400 participants, 200 migraineurs and 200 healthy controls, genotyping of RORA rs4774388 and rs11639084 polymorphisms was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction (TP-ARMS-PCR). RESULTS: The distribution of rs4774388 C/T and T/T genotypes differed significantly between the studied groups. Moreover, an association was observed between rs4774388 and migraine under the recessive mode of inheritance (P = 0.002; OR = 1.89.; CI = 1.25-2.87). The distribution of rs11639084 alleles and genotypes was not significantly different between migraineurs and healthy controls. CONCLUSION: Current results suggest RORA, as a molecular link, may explain inflammation and circadian rhythm dysfunction in migraine. Further studies in different ethnicities are required to confirm the function of RORA in migraine development.

The rs4846049 polymorphism in the 3'UTR region of the MTHFR gene increases the migraine susceptibility in an Iranian population.

INTRODUCTION: Migraine is a painful complex neurovascular disease characterized by recurrent moderate-to-severe headaches. Increased level of homocysteine is related to dilation of cerebral vessels and endothelial injury that could trigger migraine attacks. Functional polymorphisms in the MTHFR gene affect homocysteine metabolism and, therefore, play an important role in the etiology of the disease. OBJECTIVES: We aimed to investigate the possible association between MTHFR gene rs4846049, C677T, and A1298C polymorphisms and the risk of migraine in Iranian population. METHODS: In this genetic association study, 498 individuals were enrolled, including 223 migraine patients and 275 healthy controls. Genotyping was performed using tetra-primer ARMS-PCR for rs4846049 and PCR-restriction fragment length polymorphism for C677T and A1298C polymorphisms. RESULTS: The association between rs4846049 and C677T polymorphisms and migraine was observed. For the rs4846049 polymorphism, the association was detected under a dominant model (P=0.007; odds ratio [OR] =0.60; 95% confidence interval [CI], 0.41-0.87), and for the C677T polymorphism, the TT genotype frequency was significantly different in the studied groups (P=0.009; OR =2.48; 95% CI, 1.25-4.92). No significant differences in the genotype or allele frequencies were found for the A1298C polymorphism between the migraineurs and controls. CONCLUSION: Present data provide evidence for the association of rs4846049 and C677T polymorphisms in the MTHFR gene and migraine. Further studies are required to validate the significance of the studied genetic variations in diverse ethnic populations.

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.

c.376G>A mutation in WFS1 gene causes Wolfram syndrome without deafness.

Wolfram syndrome is one of the rare autosomal recessive, progressive, neurodegenerative disorders, characterized by diabetes mellitus and optic atrophy. Several other features are observed in patients including deafness, ataxia, and peripheral neuropathy. A gene called WFS1 is identified on chromosome 4p, responsible for Wolfram syndrome. We investigated a family consisted of parents and 8 children, which 5 of them have been diagnosed for Wolfram syndrome. WFS1 gene in all family members was sequenced for causative mutations. A mutation (c.376G>A, p.A126T) was found in all affected members in homozygous state and in both parents in heterozygous state. The bioinformatics analysis showed the deleterious effects of this nucleotide change on the structure and function of the protein product. As all of the patients in the family showed the homozygote mutation, and parents were both heterozygote, this mutation is probably the cause of the disease. We identified this mutation in homozygous state for the first time as Wolfram syndrome causation. We also showed that this mutation probably doesn't cause deafness in affected individuals.