The alterations of cerebrospinal fluid TNF-alpha and TGF-beta2 levels in early relapsing-remitting multiple sclerosis.

AIM OF THE STUDY: This study aimed to analyze serum and cerebrospinal fluid (CSF) concentrations of proinflammatory and anti-inflammatory cytokines produced by T regulatory (Treg) cells in early RRMS according to the 2017 McDonald criteria. CLINICAL RATIONALE FOR THE STUDY: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) with the cytokine network playing an important role. However, there is a continual lack of data regarding the immunopathogenesis of early RRMS, especially according to the 2017 McDonald criteria. MATERIALS AND METHODS: The study groups included early RRMS patients during relapse (n = 18), remission (n = 14), and the control group. The MS diagnosis was established according to the 2017 McDonald criteria. Patients were studied up to 1 year after diagnosis was made. A quantitative test kit based on ELISA was used for cytokine measurement in the serum and CSF. Comparative and correlation analyses between the levels of TNF-α, TGF-ß2, IgG index, and relapse duration were performed. RESULTS: Significantly higher CSF concentrations of TNF-α in both RRMS-relapse and RRMS-remission groups were found compared to the controls (p < 0.01). The CSF levels of TGF-ß2 in the RRMS-relapse group were significantly lower in comparison to the control group (p = 0.01). CONCLUSIONS AND CLINICAL IMPLICATIONS: An inappropriate inflammatory response seems to occur in early RRMS and includes the production of TNF-α and a decrease in TGF-ß2 release suggesting a significant Treg cells role. Further studies on the topic may contribute to developing new disease-modifying drugs and biochemical markers of the disorder.

Clinical presentation of Y189C mutation of the NOTCH3 gene in the Polish family with CADASIL.

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary, progressive ischemic disease of small vessels of the brain characterized by migraine with aura (MA), recurrent subcortical ischemic episodes, cognitive decline and psychiatric disorders. CADASIL is caused by mutations in the NOTCH3 gene. We identified the NOTCH3 Y189C mutation as a genetic cause of CADASIL in a Polish family and provided its first clinical manifestation. MATERIAL AND METHODS: The study included twelve subjects from one family. The NOTCH3 mutation, APOE and MTHFR polymorphisms were determined by high-resolution melting analyses (HRMA) and Sanger sequencing. Neuroimaging included CT and MRI. Ultrastructural examination of skin-muscle biopsy material of the proband was performed. RESULTS: The NOTCH3 Y189C mutation was present in a 36-year-old woman and her two sisters (aged 40 and 27) from 6 siblings. The MA was found in all of them, and started or became more severe after childbirth. The numerous T2/FLAIR hyperintense lesions were shown in the brain MRI. The deposition of granular osmiophilic material in the wall of small vessels of the proband observed in histopathological analysis confirmed the high degree of CADASIL severity. CONCLUSIONS: Patients with the Y189C mutation of NOTCH3 from the same family display a similar phenotype of CADASIL.

What do we currently know about the clinically isolated syndrome suggestive of multiple sclerosis? An update.

Multiple sclerosis (MS) is a chronic, demyelinating, not fully understood disease of the central nervous system. The first demyelinating clinical episode is called clinically isolated syndrome (CIS) suggestive of MS. Although the most common manifestations of CIS are long tracts dysfunction and unilateral optic neuritis, it can also include isolated brainstem syndromes, cerebellar involvement, and polysymptomatic clinical image. Recently, the frequency of CIS diagnosis has decreased due to the more sensitive and less specific 2017 McDonald criteria compared with the revisions from 2010. Not all patients with CIS develop MS. The risk of conversion can be estimated based on many predictive factors including epidemiological, ethnical, clinical, biochemical, radiological, immunogenetic, and other markers. The management of CIS is nowadays widely discussed among clinicians and neuroscientists. To date, interferons, glatiramer acetate, teriflunomide, cladribine, and some other agents have been evaluated in randomized, placebo-controlled, double-blind studies relying on large groups of patients with the first demyelinating event. All of these drugs were shown to have beneficial effects in patients with CIS and might be used routinely in the future. The goal of this article is to explore the most relevant topics regarding CIS as well as to provide the most recent information in the field. The review presents CIS definition, classification, clinical image, predictive factors, and management. What is more, this is one of very few reviews summarizing the topic in the light of the 2017 McDonald criteria.

Multiple sclerosis - the remarkable story of a baffling disease.

Multiple sclerosis has always been an enigma to its sufferers, their families, medical investigators, and clinicians. For many centuries, there have been attempts to understand its causes and nature, and to discover treatment methods. In the Middle Ages, the disease was claimed to be sent directly from God. A significant development in exploring multiple sclerosis took place in the 19th century, when Jean-Martin Charcot and his colleagues distinguished the disease, precisely described its symptoms, attempted to explain its pathophysiology, and introduced the first methods of symptomatic treatment. The 20th century was a period of discovery and development of diagnostic techniques, such as cerebrospinal fluid analysis, evoked potentials, and magnetic resonance imaging as well as an era of introducing steroid therapy for acute treatment. Currently, the dynamic development of disease modifying therapy and neuroimaging can be observed. The paper aims to delve into the remarkable history of multiple sclerosis by focusing on the earliest case reports and discovery of the disease and exploring its nature, diagnostic methods, and treatment.

Cluster Headache in a 76-year-old Woman with Onset at the Age of 74: Case Report.

Cluster headache (CH) is a rare trigeminal autonomic cephalalgia. Although its pathophysiology is not entirely understood, the hypothalamus and trigeminal nociceptive and autonomic pathways seem to play a key role in its pathology. In the majority of cases, CH begins at a young age and affects mainly men. This article presents a case of a 76-year-old woman with CH that developed at the age of 74. This is one of the first documented reports of CH with such atypical features from an epidemiologic point of view. A possibility of symptomatic cluster-like headache (CLH) attributed to cerebrovascular disease in the patient is also discussed.

Cognitive impairment in multiple sclerosis - a review of current knowledge and recent research.

Multiple sclerosis (MS) is a chronic, progressive disease of the central nervous system that is characterised by inflammatory damage to the myelin sheath. Though often neglected, cognitive impairment is a common feature of MS that affects 43-70% of patients. It has a sophisticated neuroanatomic and pathophysiologic background and disturbs such vital cognitive domains as speed of information processing, memory, attention, executive functions and visual perceptual functions. In recent years there has been growing interest in neuroimaging findings with regard to cognitive impairment in MS. The possible options of managing cognitive dysfunction in MS are pharmacologic interventions, cognitive rehabilitation and exercise training; however, not enough evidence has been presented in this field. The aim of our article is to provide current knowledge on cognitive impairment in MS based on the most recent scientific results and conclusions with regard to affected cognitive domains, neuropsychological assessment, underlying mechanisms of this disturbance, neuroimaging findings and therapeutic options.

Reversal of antithrombotic treatment in intracranial hemorrhage--A review of current strategies and guidelines.

In the last few years, there has been a rapid increase in patients being treated with various anticoagulation and antiplatelet agents. In clinical neurology, these drugs are administered for primary and secondary stroke prevention or to avoid the consequences of immobilization of severe stroke patients. Additionally, thrombolytic intravenous therapy and, recently, intra-arterial therapy for stroke have been increasingly employed all over the world. These therapies are associated with an increased risk of hemorrhage, including the most dangerous, intracranial hemorrhage. The knowledge of the standards for the treatment of hemorrhagic complications in the central nervous system is crucial for doctors in neurology and stroke units as well as in emergency rooms. Therefore, we conducted a review of various guidelines and recommendations, including manufacturers' opinions contained in the summaries of product characteristics (Polish and British or European versions), in Guidelines of the Polish Neurological Society and in international and American guidelines i.e., European Stroke Organization (ESO) and American Heart Association/American Stroke Association (AHA/ASA). In addition, we compared these guidelines with expert opinions published in recent manuscripts and manuals on intensive care in neurology.