Active Pulmonary Tuberculosis Triggered by Interferon Beta-1b Therapy of Multiple Sclerosis: Four Case Reports and a Literature Review.

In this paper, we reported on four cases of severe pulmonary active tuberculosis in patients with multiple sclerosis (MS) undergoing interferon beta-1b (IFNß-1b) therapy. Disease-modifying therapies (DMTs) in MS may increase the risk of developing active tuberculosis (TB) due to their impact on cellular immunity. Screening for latent infection with Mycobacterium tuberculosis (LTBI) should be performed, not only for the newer DMTs (alemtuzumab, ocrelizumab) but also for IFNß-1b, alongside better supervision of these patients.

Thrombotic Thrombocytopenic Purpura in Interferon Beta-1a-Treated Patient Diagnosed with Relapsing-Remitting Multiple Sclerosis: A Case Report.

BACKGROUND: Secondary thrombotic thrombocytopenic purpura (TTP) due to interferon beta-1a intramuscular (im) treatment is an uncommon adverse effect with only a few cases in multiple sclerosis patients reported worldwide. TTP together with haemolytic uremic syndrome (HUS) are classic forms of thrombotic microangiopathy, characterized by small-vessel platelet micro-thrombi that manifest clinically in a similar manner. Most common signs and symptoms include bruises and ecchymosis, neurologic symptoms and renal impairment. Interferon beta-1a represents one of the first-line therapies for relapsing-remitting multiple sclerosis due to its accessibility and efficacy. CASE PRESENTATION: A 36-year-old woman who was previously diagnosed with relapsing-remitting multiple sclerosis had received weekly intramuscular injections with beta-interferon-1a (Avonex 30 mcg). After 9 months of treatment, she presented bruises and ecchymosis on her limbs and torso, epistaxis, gingival bleeding aggravated within 48 h and a persistent headache that was non-responsive to common analgesics. Haematology tests revealed typical results for thrombotic microangiopathy, including severe thrombocytopenia (4000/mm3) and microangiopathic haemolytic anaemia with frequent schistocytes on the peripheral blood smear. Once the beta-interferon administration was ceased and upon the initiation of methylprednisolone, the symptoms remitted. CONCLUSIONS: In this case study, we portrayed the particular association between the remission phase of multiple sclerosis and the violent onset of interferon-induced thrombotic thrombocytopenic purpura.

A new era for monoclonal antibodies with applications in neurology (Review).

Medical research continues to focus on developing specific treatment strategies, including biological products that are effective and have a good safety profile. Due to their novelty, an updated overall view is offered on some neurological diseases which benefit from monoclonal antibodies (mAbs), for better treatment in clinical decisions. An extensive literature review was performed using PubMed with the following search terms: 'monoclonal antibodies' and 'history of monoclonal antibodies' and 'monoclonal antibodies in neurology'. The following information was collected: the era before the discoveries of mAbs, the stage of implementation of biotechnologies for mAbs, and the clinical trials submitted at https://clinicaltrials.gov/ with patients suffering from neurological diseases treated with mAbs. Since 2004, mAbs have been used to treat several neurological diseases, yielding new therapeutic perspectives: natalizumab, alemtuzumab and ocrelizumab for multiple sclerosis, eculizumab for myasthenia gravis, erenumab and frenazumab for migraine, galcanezumab for migraine and cluster headache, eculizumab for neuromyelitis optica spectrum disorder. As in other cases, drug repurposing is applied to monoclonal antibodies, saving time and money. These innovative therapies are more effective and can treat previously untreatable diseases. As better understanding of the pathogenic mechanisms of neurological diseases is gained, additional mAbs are expected to be developed at a lower cost and with better safety profile compared with current treatment options.

SARS-CoV-2, multiple sclerosis, and focal deficit in a postpartum woman: A case report.

SARS-CoV-2 infections raise many practical concerns in a woman with multiple sclerosis (MS) during the perinatal period. On the other hand, the impact of COVID-19 on patients with MS and disease-modifying therapies (DMTs) is unknown. We report on a female patient who was treated with interferon beta 1a (IFNB-1a) for many years for relapsing-remitting multiple sclerosis (RRMS) until December 2018. She developed COVID 19 infection in April 2020, after giving birth to a healthy baby girl, five weeks before. She developed a mild right hemiparesis 2 weeks later, without cold symptoms. On admission, PCR for SARS-CoV-2 was positive, and she received antivirals and corticotherapy. One month later, specific IgG and IgM antibodies were negative. The patient did not develop immunity to COVID-19 infection. This report raises several problems. The focal deficit could be a real relapse or a pseudo-relapse due to SARS-CoV-2 and postpartum patient vulnerability. The treatment options in this particular case raise many challenges. The absence of antibodies after a SARS-CoV-2 infection raises a big question over the acquired immunity, the increased risk of reinfection, and the subsequent evolution of MS. The standard of care for a woman with MS and COVID-19 infection during the postpartum period must be explored and more precise recommendations must be established in the future.

Vaccination in multiple sclerosis - Challenging practices (Review).

Infections are an ever-present problem in the medical community, even more so for patients with multiple sclerosis (MS), for whom these infections have been linked to relapses and neurological disabilities. Even though it was believed that MS can be caused by an infection, research does not support this theory. MS is a chronic inflammatory disease considered to be autoimmune. Vaccination is proven to be one of the most effective means to prevent infections, but still it is surrounded by controversy in the general populations, as well as in the MS group. Vaccines are generally considered safe for MS patients. The exceptions from this, which turn into contraindications, are a medical history of allergic reactions to one of the vaccine components and immunosuppressed patients in the particular case of live vaccines. Given the presumed autoimmunity of the disease, some medication for MS is immunosuppressive and any live vaccine should be administered before starting treatment. Although there is still confusion regarding this subject, the current guidelines have clearer recommendations about vaccinations in MS patients and especially in treated MS patients.

Autonomic dysfunctions in multiple sclerosis: Challenges of clinical practice (Review).

Multiple sclerosis, demyelinating, inflammatory, degenerative, and chronic disease, raises many challenges in terms of disease management. The autonomic nervous system is affected by neuroinflammation but also contributes to its maintenance and the evolution of the disease. Multiple sclerosis interfering with parasympathetic or sympathetic modulation may influence the immune response. Less attention is paid to autonomic dysfunctions, although they produce a serious impact on the quality of life. In addition to motor disabilities, patients also have non-motor dysfunctions. Regardless of its clinical forms, patients with multiple sclerosis may have autonomous disturbances such as bladder, sexual, cardiovascular, thermoregulatory, gastrointestinal dysfunction and fatigue. These must be identified based on medical history, clinical symptoms, and specific paraclinical tests. In addition to the multitude of immunomodulatory therapeutic agents that influence the progression of the disease, the therapy of autonomic dysfunctions remains difficult to address. However, their identification and treatment lead to increased quality of patient management and avoid complications of this disease.

Multiple sclerosis, human herpesvirus 4 and thyroid collision tumor: A case report.

The role of interferon ß-1b (IFNß-1b), used for multiple sclerosis (MS) therapy, in cancer occurrence is uncertain. There is evidence supporting the role of human herpesvirus 4 [Epstein-Barr virus (EBV)] in thyroid cancer and MS. Simultaneous occurrence of papillary and medullary carcinomas is rare, and its association with MS in a young woman raises questions. A 46-year-old female patient was diagnosed with relapsing-remitting multiple sclerosis in 2008. In 2018, cervical MRI detected a thyroid nodule with right cervical adenopathy. Her thyroid function was normal, but increased calcitonin levels were found (70.53 pg/ml; normal value: <9.82 pg/ml). EBV serology tested positive. Paraclinical studies ruled out multiple endocrine neoplasia syndrome. Whole thyroid resection with whole cervical lymph node dissection was performed. To our knowledge, this is the first case that describes an association between MS and thyroid collision tumors. Histological examination ascertained both papillary and medullary thyroid cancer. After surgery, the calcitonin level normalized, and the patient received a therapeutic dose of iodine-131. IFNß-1b therapy was discontinued. The coexistence of thyroid cancers in MS patients could be explained by immune-mediated inflammation. Although EBV is not the only agent responsible for the development of MS or thyroid cancers, it could be considered a contributory factor in our case. Further research on EBV involvement in the occurrence of simultaneous immune pathologies in various organs is needed to confirm these data.

Predictive factors in early onset schizophrenia.

Schizophrenia is a neurodevelopmental disorder, characterized by impairment in reasoning, affectivity and social relationships. Although the diagnosis of schizophrenia in children and adolescents has been challenged for many years, at present childhood-onset schizophrenia is considered and accepted as a clinical and biological continuum with the adult-onset disorder. The present study aimed to evaluate the influence of biological (psychiatric family history, perinatal factors), and socio-demographic factors (area of residence, gender) on the age at onset and severity of symptomatology in children and adolescent with schizophrenia. The data were collected from 2016 to 2019 and included 148 children and adolescents with schizophrenia. Data were analysed with statistical software (IBM SPSS 22, JASP and JAMOVI, Linear Regression Model, χ² tests, t-test, U-test). A positive familial history for psychiatric diseases was an important risk factor both for an early onset and for the severity of symptoms. Urbanicity was another studied risk factor, 61% of patients being from urban areas; no statistically significant correlations between urbanicity and age at onset and severity of symptoms were identified. There was no statistically significant gender difference in terms of age at onset and severity of symptoms. Moreover, no statistically significant correlations were found between perinatal factors and age at onset and severity of symptoms. Positive psychiatric family history showed a statistically significant influence on age at onset and symptoms severity in children and adolescent schizophrenia; no statistical significant impact on the aforementioned schizophrenia aspects was observed for urbanicity, gender or perinatal factors.