The diagnostic dilemma in a patient with neuroleptic malignant syndrome during the COVID-19 pandemic: A significant increase in acute phase reactants.

Key Clinical Message: In some patients, neuroleptic malignant syndrome is accompanied significant high levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). Abstract: Neuroleptic malignant syndrome (NMS) is an idiosyncratic life-threatening adverse reaction and usually triggered in response to antipsychotic drugs. In addition, leukocytosis and increased muscle enzymes levels (especially creatine phosphokinase) are observed in NMS. In addition, a transient increase in different types of acute phase reactants in NMS has been mentioned. This article describes a woman treated with haloperidol, perphenazine, escitalopram, and alprazolam because she developed catatonic symptoms after psychological stress. She suffered from NMS symptoms and had elevated CRP and ESR levels, among other signs and symptoms. Given the COVID-19 pandemic and reports of co-occurrence of catatonia and NMS and COVID-19 and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), this patient was a diagnostic dilemma. After consultation with the consultation-liaison psychiatry units, she was managed adequately with electroconvulsive therapy and lorazepam.

Pyridoxine for treatment of levetiracetam-induced behavioral adverse events: A randomized double-blind placebo-controlled trial.

BACKGROUND: Levetiracetam is a broad-spectrum antiseizure medication with known behavioral side effects. The possible beneficial effect of pyridoxine on improvement of these psychiatric problems has been suggested in few previous studies. This clinical trial aimed to investigate the effect of pyridoxine on behavioral side effects of levetiracetam in adult patients with epilepsy. METHODS: This study was a randomized double-blind placebo-controlled clinical trial on 53 adult patients with epilepsy with behavioral side effects after treatment by levetiracetam. Patients who met the study criteria were randomized to receive 40 mg/day pyridoxine or placebo. Their psychiatric state was surveyed by SCL-90-R questionnaire before and three weeks after initiation of treatment. RESULTS: There were no statistically significant differences in the behavioral adverse effects between the pyridoxine-treated group and the placebo group. CONCLUSION: Although this study showed no statistically significant beneficial effects of pyridoxine on the behavioral adverse effects of levetiracetam, placebo-controlled trials with a larger size and higher doses are needed to determine whether it is effective or not.

Atypical molluscum contagiosum on multiple sclerosis patients treated with fingolimod: A case report.

Molluscum contagiosum (MC) is a skin infection caused by a virus of the DNA poxvirus family that has already been reported by Fingolimod. We report two cases. MC can resist standard therapy and discontinuation of the fingolimod may be the only way to treat it.

The Effects of COVID-19 on Patients with Acute Ischemic and Hemorrhagic Stroke.

OBJECTIVE: The objective of this study was to evaluate how COVID-19 affects patients with acute ischemic or hemorrhagic stroke outcome. MATERIALS AND METHODS: This retrospective study was performed on adult patients (> 18 years old) with stroke (ischemic or hemorrhagic) who were admitted to hospital with or without COVID-19. The primary outcome was stroke-related disability, which was measured by mRS at baseline and discharge. Hospital duration, intensive care unit (ICU) admission, and mortality were considered the secondary outcomes. RESULTS: From February 2019 until August 2020, we recruited and analyzed 151 patients, 42 of whom had COVID-19 based on RT-PCR tests or lung CT scan findings. COVID-19 positive patients had higher baseline and final mRS scores than the control group (4.46 ± 0.67 vs 4.79 ± 0.61, P: 0.001, 3.83 ± 1.22 vs 4.46 ± 0.67, P: 0.001). Moreover, stroke patients with COVID-19 experienced a more severe disease and required a higher rate of ICU admission (17 vs 0, P:0.001) and longer hospitalization compared to those without COVID-19 (8.50 ± 7.86 vs 7.5 ± 11.20, P: 0.021). Also, mortality was higher in the COVID-19 group (19 vs 13, P:0.001). There was not any significant differences between the two groups in terms of the involvement of cerebral arteries and type of stroke. Male sex, COVID-19, and ICU admission were the main independent risk factors for death. CONCLUSION: The results of the study showed stroke patients (ischemic or hemorrhagic) with COVID-19 can have more disabilities and incur more hospital complications and mortality than non-COVID-19 patients.

Reversible blindness after erroneous prescription of closantel: A case report.

A 20-year-old girl was referred with vision loss upon closantel use. Plasma exchange and high-dose corticosteroid pulse therapy were administered. A 2.5-year follow-up showed improved vision and increased layer thickness of the peripheral nerve fiber. Early treatment with plasma exchange and high-dose corticosteroid therapy can be beneficial to reverse closantel toxicity.

Ciprofloxacin for treatment of drug-resistant epilepsy.

PURPOSE: To investigate the efficacy of short-term treatment with ciprofloxacin in alteration of gut microbiota pattern and reduction of seizure frequency in adult patients with drug-resistant epilepsy. METHODS: In a prospective study, we investigated the effect of a 5-day course of treatment with ciprofloxacin on gut microbiota pattern and seizure frequency of 23 adults with drug-resistant epilepsy. Fecal samples were collected before and after treatment and were analyzed for microbial load and species. Changes in seizure frequency were registered for 12 weeks. Responders were defined as patients who experienced ≥50 % seizure reduction in comparison to baseline. Outcome measures were specified as alteration in fecal microbial burden in days 5-7 and responder rate in 4th and 12th weeks. RESULTS: The mean baseline frequency of seizures was5.6 ±7.7 per week. All patients were on polytherapy with a mean of 3 ± 1.2 anti-seizure medications. Microbial analysis showed a considerable increase in Bacteroidetes/Firmicutes ratio after treatment. Seizure frequency significantly decreased at the end of first week and the therapeutic effect continued to week 12 (P < 0.001). The responder rate at 4th and 12th weeks were 69.6 % and 73.9 % respectively with a more prominent response in patients with symptomatic generalized epilepsy (P:0.06). CONCLUSION: Alteration of abnormal gut microbiota pattern by methods such as short-course antibiotic therapy, prescription of probiotics and fecal microbiota transplant might be effective in treatment of drug-resistant epilepsy.

Safety and efficacy of fingolimod in Iranian patients with relapsing-remitting multiple sclerosis: An open-label study.

BACKGROUND: Fingolimod was the first oral therapy approved for treating relapsing-remitting multiple sclerosis (RRMS) in 2010. This open-label study evaluated the safety and efficacy of fingolideR, 0.5 mg in Iranian MS patients during one-year follow-up. METHODS: A multicenter, open-label, longitudinal was designed to evaluate the safety and efficacy of fingolideR, 0.5 mg over a one-year follow-up period across 11 centers. The patients were visited by their neurologists every two months to evaluate possible adverse events and clinical disease activity considered by recording Kurtzke's Expanded Disability Status Scale (EDSS). RESULTS: A total of 252 patients with the mean treatment duration of 343±45.70 days were. 20 patients experienced adverse events (AEs) and serious adverse events (SAEs) such as resistant urinary tract infection (UTI), premature atrial contraction (PAC), skin allergic reaction, macular edema, chicken pox, zona, panic attacks, and exacerbations associated with steroids treatment, all of which led to FingolideR discontinuation. The mean EDSS decreased from (2.15±1.29, 95%CI: 1.99to2.32) at baseline to (1.85±1.22, 95%CI: 1.68to2.02) at 12th month (final visit) while a p-value revealed significant differences comparing baseline and final EDSS (p<0.001). Mean annualized relapse rate (ARR) of the patients in one year prior to the study was (0.006±0.016, 95%CI: 0.004to0.008) which changed to (0.005±0.016, 95%CI: 0.003to0.007) at the end of the study period. Patients with a 12-month period of fingolideR treatment experienced sustained ARR and disease progression (p<0.001). CONCLUSION: The obtained findings suggest that the administration of FingolideR, 0.5 mg (Fingolimod, Osvahpharma, Tehran, Iran) is safe and efficient for Iranian MS patients.

Resting-State Brain Network Deficits in Multiple Sclerosis Participants: Evidence from Electroencephalography and Graph Theoretical Analysis.

Background: Multiple sclerosis (MS) is a chronic inflammatory disease leading to demyelination and axonal loss in the central nervous system that causes focal lesions of gray and white matter. However, the functional impairments of brain networks in this disease are still unspecified and need to be clearer. Materials and Methods: In the present study, we investigate the resting-state brain network impairments for MS participants in comparison to a normal group using electroencephalography (EEG) and graph theoretical analysis with a source localization method. Thirty-four age- and gender-matched participants from each MS group and normal group participated in this study. We recorded 5 min of EEG in the resting-state eyes open condition for each participant. One min (15 equal 4-sec artifact-free segments) of the EEG signals were selected for each participant, and the Low-Resolution Electromagnetic Tomography software was employed to calculate the functional connectivity among whole cortical regions in six frequency bands (delta, theta, alpha, beta1, beta2, and beta3). Graph theoretical analysis was used to calculate the clustering coefficient (CL), betweenness centrality (BC), shortest path length (SPL), and small-world propensity (SWP) for weighted connectivity matrices. Nonparametric permutation tests were utilized to compare these measures between groups. Results: Significant differences between the MS group and the normal group in the average of BC and SWP were found in the alpha band. The significant differences in the BC were spread over all lobes. Conclusion: These results suggest that the resting-state brain network for the MS group is disrupted in local and global scales, and EEG has the capability of revealing these impairments.

Ischemic stroke associated with novel coronavirus 2019: a report of three cases.

INTRODUCTION: There is limited evidence about the neurological manifestations of COVID-19 in infected patients. In this report, we describe three patients with ischemic stroke associated with COVID-19 infection. METHODS: We report 3 cases of adult patients with ischemic stroke and novel coronavirus 2019 infection. Case 1 is an 88-year-old female with acute left hemiplegia and right peripheral facial paresis that she had a fever along with stroke symptoms. Case 2 is an 85-year-old female with left hemiplegia and drowsiness who had a weakness, asthenia, and dry cough 3 days before appearing stroke signs. Case 3 is a 55-year-old male with acute Broca's aphasia and right hemiplegia who experience fever and respiratory problems 3 days after admission. RESULTS: The clinical symptoms of infected patients with COVID-19 have been associated with severe symptoms of ischemic stroke. Two patients were admitted to the ICU. RT-PCR of the oropharyngeal sample was positive in three cases. All patients had the involvement of large cerebral arteries. CONCLUSION: The mechanism by which COVID-19 causes ischemic stroke is unknown but it is likely by production inflammatory cytokines or direct infection of cerebral arteries. Therefore, regarding the current situation of the COVID-19 pandemic, it is indispensable that the possible diagnosis of COVID-19 vasculopathy is considered in all ischemic strokes of unclear etiology.

Age and sex-adjusted incidence and yearly prevalence of multiple sclerosis (MS) in Mazandaran province, Iran: An 11-years study.

INTRODUCTION: The incidence rate of MS is a valuable indicator of the recent changes in the risk of this disease, and it is widely implicated for health planning purposes. OBJECTIVES: This study aims to determine the MS incidence over the past eleven years in Mazandaran province and to compare it with the other parts of Iran and the world. MATERIALS AND METHODS: This retrospective study is conducted in Mazandaran province by using registered data in the files of the patients with their consent. The yearly crude incidence rates, age, and sex-specific incidence rates and directly standardized incidence rates of this population are calculated, and the temporal changes in the incidence rates are analyzed. RESULTS: 662 (26%) male patients with the mean (SD) age of 32.6 (9.48) and 1884 (74%) female patients with the mean (SD) age of 31.9 (9.15) are studied. The direct standardized incidence rate of MS was 3.28 in 100.000 in 2008 and reached 4.17 in 100.000 in 2018, and this increase was significant (p<0.05). Also, the yearly prevalence of MS increased from 24.4 to 72.5 in this period. CONCLUSIONS: The MS incidence has increased in Mazandaran. The potential role of some genetic or environmental factors needs further investigation.

Does the multiple sclerosis (MS) map need to change again? An update of MS prevalence in Mazandaran province of Iran in 2018.

BACKGROUND: Information of Previous studies on the prevalence of MS, including our study conducted 12 years ago, used to shape global prevalence map of MS. According to those results, Iran placed in medium-prevalence MS region in the world Atlas of MS 2013.This study aimed to investigate the prevalence of MS in Mazandaran province after 12 years and the need for possible changes in the global map of the prevalence of MS. METHODS: We included all MS patients living in Mazandaran province in 2018 in this descriptive cross-sectional study. We updated our pre-existing registration questionnaires which included demographic information and medical data of MS patients by interview. We obtained the demographic profile of Mazandaran province from the most recent census in 2016 and the National Civil Registry of the Mazandaran province for calculating prevalence of MS. RESULTS: The total number of MS patients in Mazandaran was 2418 (25.8% male and 74.2% female) with a female to male ratio of 2.9. Based on the local population of 3,332,556, (50.4% male and 49.6% female), this study showed a prevalence of 72.5 per 100,000 for MS in this region. The prevalence of this disease by gender was 37.1 per 100,000 for men and 108.5 per 100,000 for women. The mean (SD) age of the patients at the time of the study was 38.5 (10.1) years with a minimum of 15 and a maximum of 75 years. The most common type of MS was Relapsing-Remitting MS with 86%. CONCLUSIONS: All recent studies showed significant upward trend in the prevalence of MS around the world. Based on the results of our study and many other studies in Iran, the Atlas of MS prevalence map needs to be update. Iran's status should be changed to the high-prevalence of MS in the new Atlas. Due to the increasing prevalence of MS, we suggest an adjustment in the Global MS Prevalence Scale.

Molecular epidemiology and antifungal susceptibility profiles of clinical Cryptococcus neoformans/Cryptococcus gattii species complex.

Introduction. Limited data regarding the epidemiology and susceptibility profiles of cryptococcosis are available in the Middle East.Aim. Our study aimed to evaluate the molecular diversity, mating types and antifungal susceptibility pattern of Cryptococcus species (n=14) isolated from 320 suspected patients with cryptococcosis.Methodology. The URA5 gene was subjected to restriction fragment length polymorphism and sequence analysis. In addition, in vitro antifungal susceptibility testing was performed by Clinical and Laboratory Standards Institute (CLSI) M27-A4 and M59 guidelines.Results. Overall, 14 (4.4 %) patients were confirmed as cryptococcosis. Based on molecular type, 85.7 and 14.3 % of the isolates were C. neoformans VN I and VN II, respectively. Phylogenetic analysis of URA5 gene sequences revealed clustering of VN I and VN II isolates into two distinct clades with a substantial difference within each molecular type. Voriconazole and 5-fluorocytosine, respectively, had the lowest (0.031 µg ml-1) and highest (8 µg ml-1) MICs. The epidemiological cutoff values (ECVs) for amphotericin B, fluconazole, voriconazole and 5-fluorocytosine encompassed ≥97 % of all 14 C. neoformans VN I species. However, according to the CLSI document M59, ECVs for itraconazole (7; 50 % of the isolates) and for posaconazole (1; 7.1 % of the isolate), were one log2 dilution higher than the wild type range. Combinations of amphotericin B with 5-fluorocytosine, amphotericin B with fluconazole and fluconazole with 5-fluorocytosine exhibited synergistic effects against 37, 31 and 12.5 % of the isolates, respectively.Conclusion. Our findings may significantly contribute to the development of management strategies for patients at a higher risk of cryptococcosis, particularly HIV-positive individuals.

Levetiracetam in genetic generalized epilepsy: A prospective unblinded active-controlled trial.

PURPOSE: To compare the efficacy and tolerability of levetiracetam (LEV) versus valproate (VPA) monotherapy in adults with genetic generalized tonic-clonic seizures alone (GTCS) and juvenile myoclonic epilepsy (JME). METHODS: This study was an open-label, active-controlled trial with a two-parallel-group design. Outcome measures including withdrawal rate and seizure freedom rate at 26th weeks and time to withdrawal, and time to first seizure were compared between LEV and VPA groups. Furthermore, tolerability and development of adverse events (AEs) were investigated and analyzed. RESULTS: One hundred and three patients enrolled the study. 71.1% of patients in LEV group and 29.3% in VPA group were female. By the end of 26th week, seizure freedom rate and withdrawal rate were 88.9% and 8.9% in LEV group and 86.2% and 10.3% in VPA group with no significant difference. Time to first seizure was longer in VPA group (p = 0.32) and time to withdrawal favored LEV (p = 0.51). At least one AE was reported in 37.7% of patients in LEV group and 55.1% in VPA group. The most common AEs were psychiatric symptoms and dizziness in those on LEV and weight gain and dyspepsia in VPA group. CONCLUSION: LEV has similar efficacy and acceptable safety in comparison to VPA in short-term treatment of patients with genetic GTCS and JME, and it could be considered as an alternative to VPA particularly in women of reproductive age.

Neurodevelopmental retardation in a baby born to a multiple sclerosis patient being treated with fingolimod.

This report is about a female child born to a multiple sclerosis mother who continued fingolimod during her first trimester of pregnancy. The child was born with normal full-term delivery but showed neurodevelopmental retardation in the following years. it is recommended that multiple sclerosis patients undergoing treatment with fingolimod use contraceptive methods for at least two months after discontinuation of the medication.

The Efficacy and Safety of Prochlorperazine in Patients With Acute Migraine: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this review was to evaluate the efficacy and safety of prochlorperazine (PCP) in patients with acute migraine headache in the emergency department (ED). METHODS: Electronic databases (Medline, Scopus, Web of Science, and Cochrane) were searched for randomized clinical trials that investigated the effect of PCP on headache relief. The outcomes were the number of patients without headache or with reduced headache severity, the number of adverse events, and the need for rescue analgesia. RESULTS: From 450 citations, 11 studies (n = 771) with 15 comparison arms met the inclusion criteria. Overall, PCP was more effective than placebo (OR = 7.23; 95% CI = 3.82-3.68), metoclopramide (OR = 2.89; 95% CI = 1.42-5.86), and other active comparators (OR = 3.70; 95% CI = 2.41-5.67) for headache relief. The odds ratio of experiencing adverse events with PCP compared with placebo was 5.79 (95% CI = 2.43-13.79). When PCP compared with other active comparators, no statistical difference was found regarding the overall number of adverse events (OR = 1.88; 95% CI = 0.99-3.59). However, PCP significantly increased the odds of akathisia/dystonia (OR = 2.55; 95% CI = 1.03-6.31). The request for rescue analgesia was significantly lower in the PCP group compared with other groups (16% vs 84%; OR = 0.16; 95% CI = 0.09-27). CONCLUSIONS: For adult patients with acute migraine, PCP could effectively abort the acute attack and reduce the request for rescue analgesia in the ED. However, compared with placebo, PCP could increase the risk of adverse events.

Eosinophilic Granulomatosis with Polyangiitis Manifested by Cholecystitis and Mononeuritis Multiplex: A Case Report.

Eosinophilic granulomatosis with polyangiitis formerly named "Churg-Strauss syndrome (CSS)" is a systemic disease with bronchial asthma, hypereosinophilia, and systemic vasculitis. We report a case of CSS with cholecystitis and mononeuritis multiplex. A 50-year-old woman with a history of sinusitis and bronchial asthma of 8 years' duration was referred with a complaint of left-hand deformity and difficulty in walking. The laboratory findings included remarkable eosinophilia, an elevated erythrocyte sedimentation rate, and a marked eosinophilic infiltration in the gallbladder biopsy. Based on the clinical features and histopathological findings, she was diagnosed with CSS and subsequently treated with prednisolone and cyclophosphamide.

A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease.

RATIONALE: There is increasing evidence to suggest the possible efficacy of Crocus sativus (saffron) in the management of Alzheimer's disease (AD). OBJECTIVE: The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD. METHODS: Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week, double-blind study of parallel groups of patients with AD. The main efficacy measures were the change in the Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Dementia Rating Scale-Sums of Boxes scores compared with baseline. Adverse events (AEs) were systematically recorded. Participants were randomly assigned to receive a capsule saffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day). RESULTS: Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting, which occurred significantly more frequently in the donepezil group. CONCLUSION: This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer's disease. This trial is registered with the Iranian Clinical Trials Registry (IRCT138711051556N1).