Predictive factors and treatment challenges in malignant progression of relapsing-remitting multiple sclerosis.

Objective: Our objective was to uncover the predictive factors that can help anticipate the malignant progression of individuals with Relapsing-Remitting Multiple Sclerosis (RRMS). Additionally, we sought to analyze and compare the response to treatment between patients with benign and malignant forms of RRMS. Methods: This cohort study included RRMS patients categorized as benign (≥10 years since disease onset, Expanded Disability Status Scale (EDSS) ≤ 1) or malignant (≤5 years since disease onset, EDSS ≥6). Patients' data, including demographics, medical history, treatment, and MRI (Magnetic Resonance Imaging) scans, were collected and statistically analyzed. Results: Among the 254 patients diagnosed with RRMS, 174 were found to have benign RRMS, while the remaining 80 were diagnosed with malignant RRMS. Notably, patients with malignant RRMS exhibited a significantly higher mean age of onset (32.00 ± 7.96 vs. 25.70 ± 17.19; P < 0.001) and a greater prevalence of males (40% vs. 18.4%; P = 0.014). Additionally, within the initial five years of diagnosis, patients with malignant RRMS experienced a higher number of relapses (median: 4 vs. 2; P < 0.001) and hospitalizations (median: 2 vs. 1; P = 0.006) compared to those with benign RRMS. Clinical presentations of malignant RRMS were predominantly characterized by multifocal attacks, whereas unifocal attacks were more prevalent in patients with benign RRMS. MRI scans revealed that malignant RRMS patients displayed a higher burden of plaques in the infratentorial and cord regions, as well as a greater number of black hole lesions. Conversely, benign RRMS patients exhibited a higher number of Gadolinium-enhanced lesions. Utilizing Disease-Modifying Therapies (DMTs) with an escalating approach has shown effectiveness in managing benign RRMS. However, it has proven insufficient in addressing malignant RRMS, resulting in frequent transitions to higher-line DMTs. As a result, it places a considerable burden on patients with malignant RRMS, consuming valuable time and resources, and ultimately yielding subpar outcomes. Conclusion: Our study identifies prognostic factors for malignant progression in RRMS, including older age of onset, male gender, increased relapses and hospitalizations, multifocal attacks, higher plaque load, and black hole lesions. The current escalation strategy for DMTs is insufficient for managing malignant RRMS, requiring alternative approaches for improved outcomes. In other words, MS is a spectrum rather than a single disease, and some patients progress to a malignant phenotype of MS that is not effectively treated by the current approach.

Simultaneous onset of Crohn's disease and Psoriasis in a Multiple Sclerosis patient treated with Teriflunomide: A novel case report highlighting potential autoimmune interactions.

Teriflunomide (TFN) is an oral Disease-modifying therapy (DMT) widely used in the treatment of relapsing forms of Multiple Sclerosis (MS). Although TFN has demonstrated efficacy in reducing MS activity, recent evidence suggests a possible association between TFN and the onset of rare and severe medical conditions. We present a novel case report of a 47-year-old woman with a history of MS who developed concurrent Crohn's disease and Psoriasis following TFN treatment. This unique occurrence has not been previously documented in the literature. The patient experienced gastrointestinal symptoms and changes in nail color while on TFN. Colonoscopy and biopsy revealed crypt architectural distortion and lamina propria expansion, indicative of Crohn's disease, while dermatological evaluation suggested Psoriasis. Consequently, TFN was discontinued and switched to alternative therapy (Glatiramer acetate), and the patient underwent close observation and regular evaluations. Three months after stopping the TFN, the patient's nail lesions disappeared completely, her abdominal pain and diarrhea were resolved, and the follow-up colonoscopy was completely normal. In this regard, the association between MS, Inflammatory Bowel Disease (IBD), and Psoriasis has been reported in previous studies, with potential involvement of Th17 and IL-17 pathways. Although gastrointestinal side effects with TFN use are typically mild and transient, rare cases of TFN-induced IBD have been reported. Dermatological disorders, including Psoriasis, have also been linked to TFN use, with similarities to our case report. Further research and awareness are warranted to better understand the potential side effects and long-term implications of TFN in the management of MS.

Association of Helicobacter pylori with migraine headaches and the effects of this infection and its eradication on the migraine characteristics in adults: A comprehensive systematic review and meta-analysis.

BACKGROUND: Migraine is one of the most common neurological disorders that can severely overshadow people's quality of life, and Helicobacter pylori infection is a health problem in different societies. During the last two decades, many original studies have been conducted on the various aspects of the relationship between these two disorders; however, they have reported different and sometimes contradictory results. METHODS: This study was conducted based on the PRISMA protocol. We performed a comprehensive literature search in the online databases up to May 2023, and 22 studies that contained original data on the relationship between H. pylori infection and migraine headaches in adults were included. For performing the meta-analysis, we calculated the odds ratios (OR) and 95% confidence intervals (CI), using a random-effects model, and to determine the possible causes of heterogeneity, we conducted a subgroup meta-analysis. RESULTS: The overall OR for the association of H. pylori infection and migraine headaches through 493,794 evaluated individuals was 2.80 [95% CI = 1.75-4.48; I2 = 89.20, p < 0.01], which reveals a statistically significant association between these disorders. It was found that the studies that were conducted in Asian regions and the recently published ones have clearly shown a higher association between migraine and H. pylori infection. On the other hand, migraine patients who are infected with H. pylori have similar signs and symptoms as H. pylori-negative migraineurs; meanwhile, the clinical trials conducted in this field strongly emphasize the benefits of eradicating H. pylori infection in migraine patients and have estimated its effectiveness in improving migraine headaches equivalent to current common migraine treatments. Furthermore, it was reported that white matter lesions were 2.5-fold higher on brain MRI in patients with H. pylori-positive migraine compared with H. pylori-negative migraineurs; however, the evidence does not support the role of oxidative stress in patients suffering from H. pylori infection and migraine and refuses the role of Cag-A-positive strains of H. pylori in migraine headaches. CONCLUSION: According to the currently available data, it seem reasonable that patients with a definite diagnosis of migraine who also suffer from gastrointestinal problems, undergo the H. pylori detection tests and if the evaluations are positive, H. pylori eradication treatment can be considered even before any migraine treatment.

Concurrent diffuse dural and leptomeningeal enhancements in brain Magnetic Resonance Imaging following a mild COVID-19 infection: A Novel Case Report and Review of Literature.

INTRODUCTION: During the COVID-19 pandemic, various complications have been reported in patients with this infection worldwide, including a wide range of neurological disorders. In this study, we have reported a novel neurological complication in a 46-years-old woman who was referred due to a headache following a mild COVID-19 infection. Also, we have had a quick review of previous reports of dural and leptomeningeal involvements in COVID-19 patients. CASE REPORT: The patient's headache was persistent, global, and compressive with radiation to the eyes. The severity of the headache was increased during the disease course and was exacerbated by walking, coughing, and sneezing but decreased with rest. The high severity of the headache disrupted the patient's sleep. Neurological examinations were completely normal, and laboratory tests did not have abnormal findings except for an inflammatory pattern. Finally, in the brain MRI, a concurrent diffuse dural enhancement and leptomeningeal involvement were observed, which is a new finding in COVID-19 patients and has not been reported so far. The patient was hospitalized and treated with Methylprednisolone pulses. After completing the therapeutic course, she was discharged from the hospital in good condition and with an improved headache. A repeated brain MRI was requested 2 months after discharge, which was completely normal and showed no evidence of dural and leptomeningeal involvements. CONCLUSION: Inflammatory complications of the central nervous system caused by COVID-19 can occur in different forms and types, and clinicians should consider them.

One-year survey of methadone-induced cardiac complications.

Background: Methadone is one of the most useful opioids that can be used to achieve many therapeutic goals, and also it may be abused as an illicit drug. Methadone can cause different gastrointestinal, neurological, and cardiac complications. This study was performed to obtain a better understanding of the cardiac side effects of methadone in patients with methadone poisoning. Methods: This cross-sectional study was performed on 210 samples in Sina Hospital of Hamadan in a one-year period from March 2019 to March 2020. After assessing patients who had methadone poisoning and completing their demographic information and evaluation of changes in patients' EKGs, the data was collected and analyzed by SPSS 16 software. Results: Out of 210 participants, 178 (84.8%) were males and the rest were females. The average age of the studied patients was 39.56 years old. The study found that 6.1% of methadone-poisoned patients were illiterate. It was found in this study that the most common cardiac complications of methadone intoxication were sinus tachycardia (20%), QT interval prolongation (6.64%), and sinus bradycardia (4.3%), respectively; nevertheless, 66.2% of patients did not have any EKG abnormalities. Conclusion: According to the findings, it is necessary to have continuous cardiac monitoring for patients with methadone intoxication and by transferring such findings to medical centers, steps can be taken to use methadone more intelligently.

Effects of blood pressure unawareness and poor adherence to antihypertensive drugs on outcomes of cerebrovascular accidents among patients with their first-ever stroke.

AIMS: Our main target was to investigate the relationship of blood pressure (BP) unawareness and poor antihypertensive drug adherence with the clinical outcomes of the stroke including hospitalization time, degree of disability, and mortality rate. METHODS AND RESULTS: In this cross-sectional study, we evaluated 530 eligible patients (male = 313; female = 217), aged 18 years and older who had a proven diagnosis of nontraumatic first-ever stroke and were referred to the Shahid Beheshti Hospital of Hamadan, Iran, during the period from March 2019 to September 2021. The prevalence of BP unawareness was 19.6%, and 31.8% of antihypertensive drug users (14.3% of all studied population) had poor drug adherence, in which, older age, male gender, marriage, rural residence, and smoking were associated with the lack of appropriate drug adherence. There was no significant difference between patients with diverse stroke types (ischemic or hemorrhagic) from the points of BP awareness and adherence to antihypertensive drugs; nevertheless, patients with a positive history of cardiac diseases had a significantly higher awareness of their BP status ( P  = 0.037). BP unawareness was associated with poor clinical prognosis, and could significantly increase stroke mortality ( P  = 0.001) and disability ( P < 0.001) rates as well as the duration of hospitalization ( P  < 0.001). Moreover, those who survived the stroke (modified Rankin Scale < 6) had the highest odds to be aware of their BP status (adjusted odds ratio [AOR] = 2.380 [95% confidence interval [CI] = 1.39-4.07]). Additionally, nonsmokers (AOR = 7.740), urban residents (AOR = 3.314), and literate patients (AOR = 2.092) had the highest odds of having appropriate drug adherence. CONCLUSION: Stroke mortality and morbidity rates can be significantly modified by persuading people to monitor their BP regularly and maximize antihypertensive medication adherence. In the meantime, increasing the literacy level in society and reducing the smoking rate can play important roles in achieving these goals.

Comprehensive comparison of clinicoradiological, laboratory, and prognostic factors of community-acquired pneumonia in diabetic and nondiabetic hospitalized patients.

Background/aim: Community-acquired pneumonia (CAP) is one of the leading infectious causes of mortality, and diabetes mellitus is a globally prevalent disease. Consequently, the cooccurrence of these two disorders can be common and create challenging medical conditions. Therefore, it was aimed to compare the various aspects of CAP in diabetic and nondiabetic patients, in order to have a comprehensive and comparative picture of the differences. Materials and methods: In this cross-sectional study, CAP patients with and without diabetes were assessed for clinicoradiological signs, laboratory features, disease severity, and pneumonia outcomes. Results: Analyzed herein were 172 CAP patients (77 had diabetes and 95 were nondiabetic). Clinical and radiological signs of pneumonia were mostly similar between the groups, except for purulent sputum, which was more prevalent among the nondiabetic patients. The laboratory results were also mostly similar. However, analysis of the outcomes and prognosis showed different results. The diabetic patients had a longer mean duration of hospital stay (8.52 days vs. 7.93 days, p = 0.015), higher median pneumonia severity based on the CURB-65 criteria (3 vs. 2, p = 0.016), and higher intensive care unit (ICU) admission requirement (22.1% vs. 7.3%, p = 0.004). Moreover, the mortality rate for the diabetic patients was nonsignificantly higher (16.8% vs. 15.7%, p = 0.453). Furthermore, the results of the logistic regression analysis showed that the diabetic patients had significantly higher odds of experiencing more severe forms of pneumonia (adjusted odds ratio (AOR): 5.77, 95% CI: 2.52-13.20), requiring ICU hospitalization (AOR: 3.56, 95% CI: 1.39-9.11), and having a longer hospital stay (AOR: 2.01, 95% CI: 1.09-3.71). In addition, although there was no significant relationship between the severity of pneumonia and the amount of glycated hemoglobin (HbA1c) in the diabetic patients (p = 0.940), the higher level of HbA1c in the nondiabetic patients was significantly correlated with a higher severity of pneumonia (p = 0.002). Conclusion: While diabetic patients with CAP have the same clinicoradiological and laboratory features as nondiabetic patients, the presence of diabetes can significantly worsen the outcomes and prognosis of pneumonia.

Effects of disease-modifying treatments discontinuation in patients with relapsing-remitting multiple sclerosis: A 5 year prospective cohort study.

BACKGROUND: One of the most challenging issues in patients with multiple sclerosis is the discontinuation of Disease-Modifying Treatments (DMTs) and subsequent complications. OBJECTIVE: We aimed to investigate the extent of adherence to DMTs in naïve multiple sclerosis patients, outcomes of non-adherence to treatments, and the risk factors that lead to drug discontinuation. MATERIALS AND METHODS: In this prospective cohort study, 288 naïve cases of Relapsing-Remitting Multiple Sclerosis (RRMS) with the age of 18 years and older were included. Their baseline EDSS (Expanded Disability Status Scale) amounts were < 2, and they were followed from 2015 for the duration of 5 years. Patients underwent clinical examination every 3 months and MRI once a year and all information was recorded. Moreover, patients that experienced pregnancy during the study period, were excluded from the main study population and evaluated separately. At the end of the 5-year period, DMT adherence rate, factors affecting treatment continuity, and the effect of treatment continuity on developed disabilities based on the EDSS were measured and analyzed by statistical software SPSS-26, CMA-3.7, and STATA-17. RESULTS: The mean age of patients was 30.01 ± 7.21 years. 12.2% of them were male and 87.8% were female. The treatment adherence rate was 82.5%, and tiredness of treatment prolongation (42.5%) was the most important reason for non-adherence to treatment. Additionally, There was a significant relationship between treatment adherence rate and the higher education level (P value = 0.016), being married (P value = 0.006), and the type of DMTs (Glatiramer Acetate (Adjusted OR = 7.7), Rituximab (Adjusted OR = 3.83), and Fingolimod (Adjusted OR = 3.81) had the highest adherence rates.). However, treatment adherence had no significant relationship with age, gender, employment, and patients' familial histories. The mean EDSS of patients with and without drug continuity after 5 years were 0.92 ± 1.09 & 1.76 ± 1.17, respectively, which showed a significant difference (P value < 0.001) in developed disabilities. Furthermore, the survival estimate of patients with drug adherence was higher than the other group. CONCLUSION: Approximately one in five patients with RRMS does not have treatment adherence during the first 5 years of treatment. Type of DMT, level of education, and marital status are factors that affect treatment adherence. Poor treatment adherence is associated with EDSS progression in multiple sclerosis patients.