Long-Term Disability Outcomes in Relapsing-Remitting Multiple Sclerosis Patients: Impact of Clinical and Demographic Factors on Disease Progression.

Background: Multiple sclerosis (MS) is a prevalent chronic inflammatory and neurodegenerative disease of the central nervous system. The main evolving forms, relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), lack clear delineation. Methods: We conducted an observational study on 523 Caucasian RRMS patients receiving first-line disease-modifying therapies (DMTs), analyzing demographic, clinical, and geographical data. Results: RRMS patients experienced a statistically significant reduction in relapse rates post-DMT initiation. Significant differences in time to reach an Expanded Disability Status Score (EDSS) of 3.0 and 6.0 were observed based on demographics and onset topography. Kaplan-Meier analysis revealed that the onset with optic or supratentorial symptoms is linked to a longer time until EDSS = 3.0 is reached. Urban origin correlated with a prolonged time until EDSS = 3.0. Gender and environment showed no significant associations with the hazard of reaching an EDSS = 6.0. Cox regression analysis revealed no significant impact of relapses on the time to reach EDSS scores of 3.0 and 6.0 in our study cohort. Conclusions: Multivariate analysis identified several predictive factors for disability progression, including environment, age at onset, and disability level at DMT initiation.

Severe Acute Motor Axonal Neuropathy associated with Influenza-A (H1N1) Infection and Prolonged Respiratory Failure - A Case Report.

Acute Motor Axonal Neuropathy (AMAN) is an immune-mediated disorder of the peripheral nervous system, part of the spectrum of the Guillain-Barre syndrome (GBS). An infectious event most often triggers it reported a few weeks before the onset. The reported case is of a 56 years-old woman who developed acute motor axonal neuropathy three weeks after respiratory infection with influenza A virus subtype H1N1. Despite early treatment with plasmapheresis and intravenous immunoglobulins, the patient remained tetraplegic, mechanically ventilated for five months, with repetitive unsuccessful weaning trails. The probable cause was considered to be phrenic nerve palsy in the context of acute motor axonal neuropathy. This case highlights that acute motor axonal neuropathy is a severe and life-threatening form of Guillain-Barre syndrome associated with significant mortality and morbidity. Neurological and physical recovery strongly depend on the inter-professional effort in an intensive care unit and neurology professionals.

Reviewing the Significance of Blood-Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment.

The disruption of blood-brain barrier (BBB) for multiple sclerosis (MS) pathogenesis has a double effect: early on during the onset of the immune attack and later for the CNS self-sustained 'inside-out' demyelination and neurodegeneration processes. This review presents the characteristics of BBB malfunction in MS but mostly highlights current developments regarding the impairment of the neurovascular unit (NVU) and the metabolic and mitochondrial dysfunctions of the BBB's endothelial cells. The hypoxic hypothesis is largely studied and agreed upon recently in the pathologic processes in MS. Hypoxia in MS might be produced per se by the NVU malfunction or secondary to mitochondria dysfunction. We present three different but related terms that denominate the ongoing neurodegenerative process in progressive forms of MS that are indirectly related to BBB disruption: progression independent of relapses, no evidence of disease activity and smoldering demyelination or silent progression. Dimethyl fumarate (DMF), modulators of S1P receptor, cladribine and laquinimode are DMTs that are able to cross the BBB and exhibit beneficial direct effects in the CNS with very different mechanisms of action, providing hope that a combined therapy might be effective in treating MS. Detailed mechanisms of action of these DMTs are described and also illustrated in dedicated images. With increasing knowledge about the involvement of BBB in MS pathology, BBB might become a therapeutic target in MS not only to make it impenetrable against activated immune cells but also to allow molecules that have a neuroprotective effect in reaching the cell target inside the CNS.

The Role of Biomarkers in Atherothrombotic Stroke-A Systematic Review.

Stroke represents the primary debilitating disease in adults and is the second-highest cause of death worldwide. Atherosclerosis, the most prevalent etiology for vascular conditions, is a continuous process that gradually creates and develops endothelial lesions known as atherosclerotic plaques. These lesions lead to the appearance of atherothrombotic stroke. In the last decades, the role of biological biomarkers has emerged as either diagnostic, prognostic, or therapeutic targets. This article aims to create a list of potential biomarkers related to atherothrombotic stroke by reviewing the currently available literature. We identified 23 biomarkers and assessed their roles as risk factors, detection markers, prognostic predictors, and therapeutic targets. The central aspect of these biomarkers is related to risk stratification, especially for patients who have not yet suffered a stroke. Other valuable data are focused on the predictive capabilities for stroke patients regarding short-term and long-term prognosis, including their influence over the acute phase treatment, such as rt-PA thrombolysis. Although the role of biomarkers is anticipated to be of extreme value in the future, they cannot yet compete with traditional stroke neuroimaging markers but could be used as additional tools for etiological diagnosis.

Therapeutic plasma exchange as a first-choice therapy for axonal Guillain-Barré syndrome: A case-based review of the literature (Review).

Guillain-Barré syndrome is an acute immune-mediated disease that affects the peripheral nervous system, with progressive motor deficit in the limbs, sometimes involvement of the cranial nerves and possible impairment of the autonomic nervous system. Due to the respiratory and autonomic nervous dysfunction, the disease has the potential to be fatal. Although modern methods of treatment have significantly improved patient prognosis, many patients nevertheless experience significant neurological sequelae. The practical applicability of plasmapheresis was illustrated in our case report. We report the case of a 27-year-old man who had a mild viral respiratory tract infection 1 week prior to the onset of disease with gradual development of a motor deficit, urinary retention, slight swallowing difficulties and mild respiratory dysfunction. Nerve conduction studies were performed and the diagnosis of acute motor axonal neuropathy phenotypic variant of Guillain-Barré syndrome was established. Autoimmune and inflammatory diseases, infectious diseases, endocrinopathies, neoplastic diseases, intoxications, metabolic diseases and vitamin deficiencies were ruled out. Our patient attended four sessions of therapeutic plasma exchange performed using peripheral venous approach with two needles with significant recovery of the motor deficit. The patient was discharged 1 week later on maintenance kinetotherapy with further favorable evolution. In conclusion, we report a good evolution as a result of therapeutic plasma exchange in a patient with acute motor axonal neuropathy phenotypic variant of Guillain-Barré syndrome. The procedure is well-tolerated and can be performed safely by peripheral approach not only in the intensive care unit but also in a neurology clinic.