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.

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.

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.

A Morphological and Immunohistochemical Study of the Tumoral and Inflammatory Cells in Pancreatic Ductal Adenocarcinoma.

This study is aimed at investigating tumoral and inflammatory cells and the significance of the prognostic factors of pancreatic ductal adenocarcinoma (PDAC); it is also aimed at determining the role of immunohistochemistry in the diagnosis and prognosis of this neoplasm. Materials and Methods. 230 cases of pancreatic ductal adenocarcinoma were included in the study group; these cases were selected from the archives of the Department of Pathology of the Fundeni Clinical Institute over a ten-year period. Immunohistochemistry was performed using the following antibodies: MUC 1, CD 34, Factor VIII, CD 68, MMP-7, CEA, p21, p53, and Ki 67. Results. There were 133 male (57.8%) and 97 female (42.2%) patients included in this study, with ages between 20 and 81 years old (mean age: 58.2 years) and with tumors located in the pancreatic head (n = 196; 85.2%), pancreatic body (n = 12; 5.2%), and pancreatic tail (n = 20, 8.7%), as well as panpancreatic tumors (n = 2; 0.9%). Patients presented with early stages (IA and IB), with low pathologic grade (G1), with small size tumors (less than 1-1.5 cm), with tumors located in the head of the pancreas, (p53: negative; p21: positive; and CD 68: positive in peritumoral tissue), with low nuclear index (Ki 67 < 10%), without metastases at the time of surgery (had a better prognosis), and with a survival rate of about 7 months. Conclusions. Immunohistochemistry is useful for an accurate diagnosis, differential diagnosis, and establishment of additional factors that might have a prognostic importance. It is recommended to study peritumoral tissue from the quantitative and qualitative points of view to increase the number of prognostic factors. This study represents a multidisciplinary approach, and it is a result of teamwork; it presents histopathological methods of examination of this severe illness and describes only a part of the scientific effort to determine the main pathological mechanisms of this neoplasm.

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.

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.

Does Frailty Predict Health Care Utilization in Community-Living Older Romanians?

Background. The predictive value of frailty assessment is still debated. We analyzed the predictive value of frailty of independent living elderly. The outcomes variables were visits to the general practitioner, hospital admission, and occurrence of new health problems. Methods. A one-year follow-up study was executed among 215 community-living old Romanians. General practitioners reported the outcome variables of patients, whose frailty was assessed one year before, using the Groningen Frailty Indicator. The predictive validity is analyzed by descriptive and regression analysis. Results. Three-quarters of all participants visited their general practitioner three times more last year and one-third were at least once admitted to a hospital. Patients who scored frail one year before were more often admitted to a hospital. Visits to the general practitioner and occurrence of new health problems were not statistically significant related to frailty scores. The frailty items polypharmacy, social support, and activities in daily living were associated with adverse outcomes. Conclusions. The predictive value of frailty instruments as the Groningen Frailty Indicator is still limited. More research is needed to predict health outcomes, health care utilization, and quality of life of frailty self-assessment instruments. Validation research on frailty in different "environments" is recommended to answer the question to what extent contextual characteristics influence the predictive value.

Assessment of care problems in Romania: feasibility and exploration.

OBJECTIVES: The objective of this study was to study the feasibility of a recently developed instrument, LPZ-International, which assesses care problems in health care, and to describe the prevalence of care problems in Romanian health care institutions. Large differences exist in care services in Europe. Data on quality of care are absent or incomplete in Central-Eastern European countries. These countries, including Romania, have faced dramatic socioeconomic changes, which led to negative changes in quality of care. DESIGN: Cross-sectional study. SETTING: Hospital wards, mental care institutions, and nursing homes. PARTICIPANTS: Nine health care institutions and admitted 394 patients. MEASURES: LPZ-International was introduced in 9 health care institutions in Romania. Assessed care problems included pressure ulcers, urinary and fecal incontinence, malnutrition, falls, and physical restraints. The data were collected between November 2013 and March 2014. Two health care professionals completed the questionnaire by hand at the patient's site. RESULTS: Six of the 9 health care institutions and 90% of the patients participated, which indicates the feasibility of LPZ-International, as did the completeness of the questionnaire. The data showed a high consistency and only a few were missing. The most frequent care problem was urinary and fecal incontinence, especially in the nursing home. Pressure ulcers and malnutrition were less frequent care problems in Romanian patients. Physical restraints were frequently applied in the nursing home and geriatrics and oncology wards. CONCLUSIONS: LPZ-International is a feasible instrument to assess care problems. The differences between wards and countries in the prevalence of care problems indicate differences in quality of care and the need for high-quality, comparative research.

The psychometric qualities of the Groningen Frailty Indicator in Romanian community-dwelling old citizens.

BACKGROUND: Primary health care may play an important role in identifying persons at risk for frailty. The Groningen Frailty Indicator (GFI) is considered a valid instrument to assess frailty in old age. However, it is not tested yet in a different cultural context. The aim of this study is to analyse the construct, content and criterion validity of the GFI in independent-living old Romanians. METHODS: Twenty-two GPs participated in this study. They have sent he GFI questionnaire to 215 patients of 65 years and over. The GPs assessed the frailty of the patients, independently from the questionnaire. RESULTS: The mean age of the respondents was 74.9 years. The mean GFI score was 5.5 (SD 2.9). Three-quarters of the respondents fit into the 'moderate' or 'severe' frailty category. Citizens 80 years old and older scored higher in terms of frailty. Ninety-eight per cent of the respondents completed at least 75% of the GFI items. The construct validity was good (Cronbach's alpha 0.746). All the items contributed statistically significant to the total GFI score (content validity). The old citizens who were rated as frail by the GPs (criterion validity) had a higher GFI score CONCLUSION: This study showed the GFI to be a feasible and valid instrument to assess frailty in independent-living old Romanians. Compared with the Dutch old, the prevalence of frailty in independently living old Romanians is high. Further research is needed to determine the appropriate cut-off points in the GFI scores in different care systems.

Health status of independently living older adults in Romania.

AIM: Aging is affecting health care all over Europe, but it is expected to have a much greater impact in Eastern Europe. Reliable data on various indicators of health of older adults in Eastern Europe are lacking. The objectives of the present study were to describe the health of older Romanian adults, and to examine its relationship with sociodemographic, psychological and social factors. METHODS: This cross-sectional study used a stratified sample of 600 independent-living older Romanian adults from the great metropolitan area of Bucharest; 549 citizens aged ≥ 65 years participated. Data were collected by a mailed questionnaire and interviews. Measurements included self-rated health, the number of chronic conditions, the Short Form-20, the Eysenck Personality Questionnaire and Social support. RESULTS: Romanian older adults rate their health as "fair". On average, they report three chronic conditions. They more frequently have problems in executing daily activities as compared with older adults from other European countries. Three components of health are identified: independent functioning, suffering from chronic diseases and psychological health. Regression analysis shows that age, education and social support are related to each component, and neuroticism and extraversion to two components of health. CONCLUSIONS: A comparison with international data shows various indicators of health of older Romanian adults to be relatively worse. The three identified components of health offer opportunities for an integrated approach to deal with the health care needs of older citizens.