Iraqi experts consensus on the management of relapsing remitting multiple sclerosis in adults.

OBJECTIVE: In Iraq, a lack of evidence-based management protocols for diagnosing, treating, and managing multiple sclerosis (MS) poses risks of suboptimal outcomes and clinical practice variability and potential harm to the patients. This study aimed to develop consensus recommendations regarding the diagnosis and management of MS in Iraq, specifically focusing on treatment-naïve patients, suboptimal responders, and women of childbearing age during preconception, pregnancy planning, and lactation.A survey was conducted to collect feedback from a panel of ten key opinion leaders (KOLs), who evaluated and discussed the statements to determine agreement levels. The mini-Delphi method was employed to establish a consensus on the management recommendations, and a meeting was held to analyze the responses and ensure that the recommendations were based on current evidence and followed a consensus-driven approach. RESULTS: The Revised McDonald Criteria is recommended for MS diagnosis, which includes evidence of dissemination of disease characteristics in space and time. Disease activity and progression can be monitored using relapses, MRI activity, and short-term disability progression. Experts suggest initiating treatment at diagnosis using higher efficacy medications, such as cladribine, ocrelizumab, natalizumab, or rituximab, for patients with high disease activity after careful risk stratification. Injectable interferon preparations have a tolerable risk profile but have drawbacks, such as the route and frequency of administration. Overall, disease-modifying therapies (DMTs) have shown efficacy in reducing relapse rates and short-term disability. CONCLUSION: This article presents expert panel recommendations for managing MS in Iraq, taking into account international guidelines, medication updates, and local resources. However, practical questions remain regarding the real-world use of disease-modifying therapies (DMTs). Personalizing treatment based on disease severity, prognosis, and individual risk factors while adhering to guidelines is crucial. A collaborative approach between healthcare providers and patients, considering individual preferences, is vital for achieving treatment goals.

MRI assessment of cervical spinal cord cross-sectional area in patients with multiple sclerosis.

Objectives: Spinal cord abnormalities including cervical cord atrophy are common in multiple sclerosis (MS). This study aimed to assess the cervical spinal cord cross-sectional area (CSA) using magnetic resonance imaging (MRI) in MS patients. Materials and Methods: Sixty participants were enrolled in this study (16 male and 44 female), 30 patients with MS, diagnosed according to the revised McDonald criteria, and 30 apparently healthy individuals as the control group. CSA of the spinal cord was measured on axial T2-weighted images of the cervical MRI studies from C2 to C7 vertebral levels. Results: There was a significant difference between MS patients and the control group in mean CSA at a different level. The mean CSA at C2, in MS cases, was significantly lower than controls (67.7 ± 9.4 mm2 vs. 81.3 ± 4.6 mm2). Similarly, the mean CSA at C7 (64.4 ± 9.9 mm2) and average C2-7 (68 ± 9.1 mm2) of MS cases were significantly lower than the control. There was a strong inverse correlation between mean cervical cord CSA and duration of the disease and disability score. The reduction in cervical cord CSA was more prominent in patients with secondary progressive MS. There was no significant difference regarding age, gender, type of treatment, or the number of cervical cord lesions. Conclusion: The mean CSA was significantly lower in patients with MS than in the control group and was lesser in progressive types. Patients with a longer duration of MS and a high disability score tend to have smaller CSA.

Mood Symptoms and Chronic Fatigue Syndrome Due to Relapsing-Remitting Multiple Sclerosis Are Associated with Immune Activation and Aberrations in the Erythron.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune and neuroinflammatory disease of the central nervous system characterized by peripheral activation of immune-inflammatory pathways which culminate in neurotoxicity causing demyelination of central neurons. Nonetheless, the pathophysiology of relapsing-remitting MS (RRMS)-related chronic fatigue, depression, anxiety, cognitive impairments, and autonomic disturbances is not well understood. OBJECTIVES: The current study aims to delineate whether the remitted phase of RRMS is accompanied by activated immune-inflammatory pathways and if the latter, coupled with erythron variables, explain the chronic fatigue and mood symptoms due to RRMS. MATERIAL AND METHODS: We recruited 63 MS patients, 55 in the remitted phase of RRMS and 8 with secondary progressive MS, and 30 healthy controls and assessed erythron variables, and used a bio-plex assay to measure 27 serum cytokines. RESULTS: A significant proportion of the MS patients (46%) displayed activation of the immune-inflammatory response (IRS) and compensatory immune response (CIRS) systems, and T helper (Th)1 and Th17 cytokine profiles. Remitted RRMS patients showed increased chronic fatigue, depression, anxiety, physiosomatic, autonomic, and insomnia scores, which could partly be explained by M1 macrophage, Th1, Th-17, growth factor, and CIRS activation, as well as aberrations in the erythron including lowered hematocrit and hemoglobin levels. CONCLUSIONS: Around 50% of remitted RRMS patients show activation of immune-inflammatory pathways in association with mood and chronic-fatigue-like symptoms. IRS and CIRS activation as well as the aberrations in the erythron are new drug targets to treat chronic fatigue and affective symptoms due to MS.

Expert opinion on the pharmacological management of multiple sclerosis in women of childbearing age in Iraq.

Background: Multiple sclerosis (MS) is often diagnosed in women of childbearing age (WCBA), with a mean age of onset of 30 years. Women with MS have long been cautioned to carefully plan their pregnancies and, traditionally, disease-modifying therapies (DMTs) have not been recommended for use in patients engaged in family planning. In 2020, the United States Food and Drug Administration (FDA) approved a label update for interferon beta (IFN ß) by adding new safety data on pregnancy and breastfeeding. Because current management guidelines do not yet reflect the recent label update, a panel of neurology experts from Iraq decided to discuss the potential need for changes in treatment strategies in Iraq. Methods: A panel of experts consisting of 8 neurologists from Iraq and one international neurology expert from Germany convened to develop an expert opinion that would provide practical guidance for the pharmacological management of WCBA with MS in Iraq. They considered the latest label update and relevant published literature, along with local clinical practice and available resources. Results: Interferon and Glatiramer acetate have no evidence of harm during pregnancy. IFN ß can be continued safely through pregnancy. Switching treatment during pregnancy is generally not recommended. Short-term intravenous methylprednisolone can be used to treat disabling relapses. Conclusion: Given the complexity of managing MS in pregnant women, it is the opinion of the expert panel that family planning should be discussed early in the disease course, planned pregnancy should be encouraged, and open communication with patient for her treatment decisions is paramount. Patients who are engaged in family planning are no longer discouraged from treatment with some of the currently available DMTs.

Epidemiology of multiple sclerosis in Iraq: retrospective review of 4355 cases and literature review.

OBJECTIVES: Multiple sclerosis (MS) is a progressive demyelinating and degenerative disease of the CNS, which is highly variable geographically. The objectives are to establish comprehensive nationwide MS epidemiological data and compare it with similar studies conducted in regional and international communities. To the best of our knowledge, this is the first nationwide comprehensive epidemiological study conducted in Iraq. METHODS: This retrospective study is including 4355 MS cases from the 10 officially authorized MS clinics in Iraq from January 2000 to December 2018. All cases were diagnosed according to McDonald's criteria 2010, new cases diagnosed according to the new criteria of McDonald's criteria 2018. All patients' records were reviewed by the scientific committee. RESULTS: Our study found that 68.51% of MS were females with female-to-male ratio 2.18:1 and 4.07% of patients were diagnosed before they reached 18 years of age. The mean age was 32.3 ± 9.8. The prevalence was found to be 11.73/100,000; it was 16.2/100,000 among females and 7.3/100,000 among males. The incidence was 0.05 in the year 2000 and 1.5 in the year 2017. Initial symptoms were visual 32.06%, motor 28.11%, and 25.58% were sensory symptoms, and 89.97% of the clinical form was relapsing/remitting MS (RRMS) and 81.65% of patients were on first-line treatment. Meanwhile, 66.97% of cases were diagnosed within weeks or months from symptom onset. Summer had the most frequencies regarding birth season. CONCLUSIONS: MS has a significantly increased incidence in Iraq, while prevalence is low compared to neighboring countries. RRMS was the most common clinical form and visual symptoms showed the highest frequency of the first presenting symptoms.

Fatal Case of COVID-19 Pneumonia Associated with Acute Myelopathy.

In December 2019, a novel coronavirus outbreak with multiple system involvement started initially in Wuhan City, Hubei Province of China. Coronavirus disease 2019 (COVID-19) infection is a systemic disorder typically presenting with fever, fatigue, and upper and lower respiratory symptoms, although neurological manifestations are increasingly reported, but pathological mechanisms have yet to be established. The symptoms of infection with COVID-19 are dependent on the patient's age and underlying medical illness, and on the condition of the immune system. Neurotropic and neuroinvasive capabilities of coronaviruses have been described in humans. We herein report a patient infected with COVID-19 who developed pneumonia associated with acute progressive myelopathy. Neurological examination revealed progressive flaccid areflexic paralysis of lower limbs over 3 days with retention of urine and sensory level at 10th spinal thoracic segment (T10). The patient had a positive nasopharyngeal swab for COVID-19 at the onset of the neurological symptoms. This case of acute progressive myelopathy adds further evidence of the complications of severe COVID-19 infection, and we are dealing with a virus of unpredictable behavior. Since this virus neurotropism is not clear yet, further investigations should be conducted on the mechanism of possible neurological infection in patients with COVID-19.

Improvement of spinal contusion model by cotransplanting bone marrow stromal cells and induced BMSCs into oligodendrocytes-like cells.

BACKGROUND: Demyelination is a common lesion in spinal cord injury, cell therapy is one of the approaches for replacing the lost oligodendrocytes. In this study, bone marrow stromal cells (BMSCs) have been transdifferentiated into oligodendrocyte-like cells (OLCs) and used in cytotherapy of contused spinal cords in rats. METHODS: The BMSCs were collected from the rat long bones, and cultured and characterized by different markers, then they were preinduced with dimethyl sulfoxide followed by retinoic acid, and then the preinduced cells were induced with combination of basic fibroblast growth factor, platelet-derived growth factor and heregulin, followed by triiodothyronine. The OLCs were transplanted in the contused spinal cords of the rats, combined with undifferentiated BMSCs. Specific markers were used in order to characterize the cells by immunohistochemistry and real-time polymerase chain reaction. The BMSCs showed typical immnuoreactivity to the markers, and the OLCs were immunostained with specific markers. RESULTS: There was an improvement in the Basso, Beattie and Bresnahan score with reduction in the cavitation in the contused rats treated with OLCs combined with BMSCs. The transplanted cells were detected in the contused spinal cord. CONCLUSIONS: The combination of the transdifferentiated BMSCs into OLCs with the undifferentiated BMSCs improved the contused spinal cord.

Creatine Enhances Transdifferentiation of Bone Marrow Stromal Cell-Derived Neural Stem Cell Into GABAergic Neuron-Like Cells Characterized With Differential Gene Expression.

Creatine was reported to induce bone marrow stromal cells (BMSC) into GABAergic neuron-like cells (GNLC). In a previous study, creatine was used as a single inducer for BMSC into GNLC with low yield. In this study, BMSC-derived neurospheres (NS) have been used in generating GABAergic phenotype. The BMSC were isolated from adult rats and used in generating neurospheres and used for producing neural stem cells (NSC). A combination of all-trans-retinoic acid (RA), the ciliary neurotrophic factor (CNTF), and creatine was used in order to improve the yield of GNLC. We also used other protocols for the transdifferentiation including RA alone; RA and creatine; RA and CNTF; and RA, CNTF, and creatine. The BMSC, NSC, and GNLC were characterized by specific markers. The activity of the GNLC was evaluated using FM1-43. The isolated BMSC expressed Oct4, fibronectin, and CD44. The NS were immunoreactive to nestin and SOX2, the NSC were immunoreactive to nestin, NF68 and NF160, while the GNLC were immunoreactive to GAD1/2, VGAT, GABA, and synaptophysin. Oct4 and c-MYC, pluripotency genes, were expressed in the BMSC, while SOX2 and c-MYC were expressed in the NSC. The activity of GNLC indicates that the synaptic vesicles were released upon stimulation. The conclusion is that the combination of RA, CNTF, and creatine induced differentiation of neurosphere-derived NSC into GNLC within 1 week. This protocol gives higher yield than the other protocols used in this study. The mechanism of induction was clearly associated with several differential pluripotent genes.

Differentiation of neurosphere-derived rat neural stem cells into oligodendrocyte-like cells by repressing PDGF-α and Olig2 with triiodothyronine.

One of the approaches for treating demyelination diseases is cytotherapy, and adult stem cells are potential sources. In this investigation, we tried to increase the yield of oligodendrocyte-like cells (OLCs) by inducing neural stem cells generated from BMSCs-derived neurospheres, which were used for deriving the neural stem cells (NSCs). The latter were induced into OLCs by heregulin, PDGF-AA, bFGF and triiodothyronine (T3). The BMSCs, NS, NSCs and OLCs were characterized by using immunocytochemistry for fibronectin, CD44, CD90, CD45, Oct-4, O4, Olig2, O1 and MBP markers. PDGF receptor α (PDGFR-α), Olig2 and MOG expression were evaluated by RT-PCR. The BMSCs expressed CD44, CD90, CD106 and Oct-4; the NSCs were immunoreactive to nestin and neurofilament 68. Incubation of the NSCs for 4 days with heregulin, PDGF-AA and bFGF resulted in their induction into oligodendrocyte progenitor-like cells (OPLCs), which immunoreacted to O4, Olig2 and O1, while Olig2 and PDGFR-α were detected by RT-PCR. Replacing heregulin, PDGF-AA and bFGF with T3 for 6 days resulted in repression of O4, O1, Olig2 and PDGFR-α. The OLCs were co-cultured with motoneurons resulted in induction of MOG and MBP, which were expressed in functional OLCs. The latter can be generated from BMSCs-derive NS with high yield.