BACKGROUND: A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. METHODS: Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. RESULTS: CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. CONCLUSIONS: In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.

• MeSH
• Biomarkers * blood   MeSH
• Claudin-3 * metabolism   MeSH
• Adult MeSH
• Intestinal Barrier Function MeSH
• Middle Aged MeSH
• Humans MeSH
• Permeability * MeSH
• Fatty Acid-Binding Proteins * blood   MeSH
• Multiple Sclerosis * physiopathology   metabolism   blood   MeSH
• Intestinal Mucosa metabolism   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The IgM-related peripheral neuropathies (IgM-PN) are a group of chronic disorders characterized by the presence of monoclonal IgM that may be associated with one of several diseases affecting the peripheral nerves. In many cases, there is a monoclonal IgM associated with activity against neural targets, leading to progressive peripheral nerve demyelination. Neurological symptoms in this setting can also result from direct invasion of the peripheral or central nervous system by lymphoplasmacytic cells (neurolymphomatosis and Bing-Neel syndrome respectively) or via other mechanisms (for example AL amyloid deposition or cryoglobulinemic vasculitis). There is an expanding array of treatment options, but high-quality data are sparse. Diagnostic accuracy is important and needs collaboration between hematologists and neuromuscular specialists to determine the sequence and intensity of investigations. Appropriate causal attribution to the IgM disorder is essential to enable the correct therapeutic intervention. The aims of treatment intervention should be clear and realistic. Consistent and clinically meaningful measures are needed to capture treatment success. Despite therapeutic advances, many patients experience persistent disability, highlighting the need for further research.

• MeSH
• Immunoglobulin M * immunology   MeSH
• Humans MeSH
• Disease Management MeSH
• Peripheral Nervous System Diseases * therapy   diagnosis   etiology   immunology   MeSH
• Waldenstrom Macroglobulinemia * therapy   complications   diagnosis   immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Consensus Development Conference MeSH

Autoimunitní encefalitidy jsou autoimunitně podmíněná onemocnění centrálního nervového systému s převážným postižením mozkové kůry. Jedná se o heterogenní skupinu stavů projevující se nově vzniklým neurologickým a psychiatrickým deficitem u dříve zdravých dětí. Tyto poruchy se odlišují závažností, klinickým průběhem a etiologií. Na rozdíl od dospělé populace u dětí převládají neparaneoplastické encefalitidy. V rámci prognózy a léčby je nejdůležitější identifikovat přítomnost antineuronálních protilátek. Rozlišujeme protilátky proti povrchovým antigenům nebo intracelulárním antigenům. Autoimunitní onemocnění příznivě reagují na imunoterapii, proto je nezbytná rychlá diagnostika a včasná léčba, která může vést k rychlejší úzdravě, snížení frekvence relapsů a kognitivního deficitu. Naše sdělení se zaměřuje na diagnostické a léčebné zkušenosti s nejfrekventovanějšími autoimunitními encefalitidami a protilátkami zprostředkovanými demyelinizačními syndromy v dětském věku ve Fakultní nemocnici Ostrava.

Autoimmune encephalitis is a group of autoimmune-related diseases of the central nervous system with the predominant involvement of the cerebral cortex. It is a heterogeneous group of conditions manifested by newly emerging neurological and psychiatric deficits in previously healthy children. These disorders differ in severity, clinical course, and aetiology. Unlike the adult population, non-paraneoplastic encephalitis is prevalent in children. Antineuronal antibodies are the most critical prognostic and therapeutic indicators. Antibodies are directed either against surface antigens or intracellular antigens. Autoimmune diseases respond favourably to immunotherapy. Therefore, rapid diagnosis and timely treatment are essential and can lead to faster recovery and lower rates of relapses and cognitive deficits. This article focuses on the diagnostic and therapeutic experience with the most common types of autoimmune encephalitis and antibody-mediated demyelinating syndromes in childhood at the University Hospital Ostrava.

• MeSH
• Autoimmune Diseases of the Nervous System * diagnosis   drug therapy   MeSH
• Autoantibodies analysis   immunology   MeSH
• Demyelinating Autoimmune Diseases, CNS diagnosis   drug therapy   MeSH
• Child * MeSH
• Immunotherapy methods   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Neurologic Manifestations MeSH
• Paraneoplastic Syndromes etiology   complications   MeSH
• Check Tag
• Child * MeSH
• Humans MeSH

Chronická zápalová demyelinizačná polyneuropatia (CIDP) je získaná, imunitne sprostredkovaná neuropatia, spôsobená zápalom periférnych nervov a nervových koreňov. Jedná sa o najčastejšiu chronickú autoimunitnú polyneuropatiu, ktorá je stále poddiagnostikovaným ochorením. Ak sa dlhodobo nelieči alebo je liečená nesprávne, môže viesť k závažnému zneschopneniu s narušením jemnej motoriky, chôdze a celkovej mobility pacienta. CIDP býva asociovaná s viacerými ochoreniami ako sú diabetes mellitus, monoklonálne gamapatie, infekcia HIV, malignity či viaceré systémové ochorenia. V poslednej dobe pribúda referencií, že prevalencia CIDP má tendenciu byť vyššia u diabetikov, najmä u pacientov vo vyššom veku. Diagnostika CIDP u pacienta s diabetom je náročná, pretože superponované axonálne poškodenie pri možnej diabetickej neuropatii môže zakryť typické demyelinizačné elektrofyziologické nálezy. Na druhej strane diabetická polyneuropatia môže spôsobiť zvýšenie hladiny proteínov v likvore. Vo vysvetlení asociácie týchto dvoch ochorení existuje stále viacero kontroverzií. Stále nemáme adekvátny diagnostický nástroj pre jasné definovanie CIDP u diabetika. Výzvou pre neurológov je práve identifikácia potenciálnych biomarkerov CIDP u diabetického pacienta, pretože CIDP je liečiteľné ochorenie.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, immune-mediated neuropathy caused by inflammation of peripheral nerves and nerve roots. It is the most common chronic autoimmune polyneuropathy, which is still considered underdiagnosed. If it remains untreated or improperly treated for a long time, it can lead to severe disability with impairment of the patient‘s fine motor skills, walking, and general mobility. CIDP may be associated with several diseases such as diabetes mellitus, monoclonal gammopathy, HIV infection, malignancies, or several systemic diseases. Recently, there have been several references that the prevalence of CIDP tends to be higher in diabetics, especially in older patients. Diagnosing CIDP in a patient with diabetes is challenging, because superimposed axonal damage in possible diabetic neuropathy can obscure typical demyelinating electrophysiological findings. On the other hand, diabetic polyneuropathy can cause elevated protein in cerebrospinal fluid. There are still many controversies in explaining the association of these two diseases. We still do not have an adequate diagnostic tool to clearly define CIDP in diabetic patients. The identifying a potential biomarkers of CIDP in diabetic patients is a challenge for neurologists, as CIDP is a treatable disease.

• MeSH
• Biomarkers MeSH
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating * diagnosis   therapy   MeSH
• Diabetes Mellitus, Type 2 complications   MeSH
• Diabetic Neuropathies diagnosis   MeSH
• Diagnosis, Differential MeSH
• Electromyography MeSH
• Diabetes Complications MeSH
• Middle Aged MeSH
• Humans MeSH
• Gait Disorders, Neurologic diagnosis   etiology   therapy   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

Roztroušená skleróza (RS) je chronické autoimunitní onemocnění s prvky neurodegenerace, které postihuje nejčastěji mladé dospělé ve věku 20-40 let. Onemocnění je 3× častější u žen než u mužů. Mezi nejčastější symptomy RS patří poruchy zraku, senzitivní, motorické a sfinkterové dysfunkce. Mezi příznaky, které mohou být poněkud opomíjené, ale přesto velmi ovlivňují kvalitu života a celkový zdravotní stav, patří i poruchy polykání. V uvedené videokazuistice prezentujeme mladou pacientku, u které byla dysfagie jedním z prvních symptomů RS. V rámci kazuistiky popisujeme diagnostiku dysfagie a i následný komplexní terapeutický přístup, který zahrnoval jednak terapii RS, ale i cílenou pravidelnou logopedickou péči.

Multiple sclerosis is a chronic autoimmune disease affecting the central nervous system (CNS) and is characterized by inflammation, demyelination, gliosis, and neuronal loss. This condition manifests with a wide range of neurological symptoms, such as vision impairment, numbness and tingling, focal weakness, bladder and bowel dysfunction, and cognitive impairment. Swallowing disorders are among the symptoms that may be somewhat neglected but nevertheless greatly affect quality of life and overall health. Multiple sclerosis most often affects young adults aged 20-40 years. The disease is 2 to 3 times more common in women than in men. In this video case report, we present a young patient in whom dysphagia was one of the first symptoms of MS. In the case report, we describe the diagnosis of dysphagia and the subsequent complex therapeutic approach, which included both therapy for MS and targeted regular speech therapy.

• Keywords
• ofatumumab,
• MeSH
• Antigens, CD20 pharmacology   MeSH
• Diagnosis, Differential MeSH
• Antibodies, Monoclonal, Humanized pharmacology   classification   therapeutic use   MeSH
• Speech-Language Pathology methods   MeSH
• Humans MeSH
• Young Adult MeSH
• Deglutition Disorders * diagnosis   etiology   drug therapy   rehabilitation   MeSH
• Multiple Sclerosis * diagnosis   drug therapy   complications   MeSH
• Check Tag
• Humans MeSH
• Young Adult MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH

Pronator teres syndrome is characterized by compression of the median nerve, leading to dysfunction of the affected limb. Median nerve entrapment causes paresthesia, changes in sensitivity, and loss of strength in the fingers, in addition to causing loss of hand dexterity. The diagnosis of pronator teres syndrome is complicated, due to its similarity with other neuropathies of the median nerve. So, it is important to emphasize the need for a physical examination together with imaging tests, especially ultrasound, for its correct diagnosis. We report the case of a 28-year-old woman who complained of tingling for ten years in the proximal third of the left forearm at rest that worsens on exertion and weakness if not moving. On physical examination, she has no limitation of movement but refers to a feeling of weakness and numbness in his forearm. Ultrasonography demonstrates compression of the median nerve between the ulnar and humeral heads of the pronator teres muscle, a finding confirmed by magnetic resonance imaging and electroneuromyography. The patient was treated with physiotherapy presenting improvement of symptoms after 45 days.

• MeSH
• Arthrogryposis MeSH
• Adult MeSH
• Electromyography methods   MeSH
• Hereditary Sensory and Motor Neuropathy MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Median Neuropathy diagnosis   MeSH
• Forearm MeSH
• Ultrasonography methods   MeSH
• Nerve Compression Syndromes diagnosis   physiopathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

INTRODUCTION: Multiple Sclerosis (MS), a debilitating central nervous system (CNS) disorder, is characterized by inflammation, demyelination, and neuronal degeneration. Despite advancements in immunomodulatory treatments, neuroprotective or restorative strategies remain inadequate. Our research is focusing on the potential of the positive allosteric modulator of AMPA receptors (AMPA-PAM), PF4778574, in addressing MS symptoms. METHODS: We utilized the MOG35-55 induced experimental autoimmune encephalomyelitis (EAE) model in C57BL6J mice to examine PF4778574's therapeutic and prophylactic efficacy. Our comprehensive approach included clinical scoring, optical coherence tomography (OCT), optomotor response (OMR) and histological assessments. Additionally, we explored the effects of PF4778574 in comparison and in combination with the immunomodulatory agent fingolimod, and investigated the impact on Cuprizone induced toxic demyelination. RESULTS: Prophylactic administration of PF4778574 showed notable improvement in clinical EAE indices and reduction in neuronal loss. While it did not diminish microglial activity, it reduced demyelinated areas in optic nerves and in the corpus callosum. Both PF4778574 and fingolimod significantly enhanced clinical EAE scores and decreased demyelination. However, their combination did not yield additional benefits. In the cuprizone model, PF4778574 increased oligodendrocyte precursor and mature myelin-forming cells, suggesting a pro-remyelinating effect. DISCUSSION: PF4778574 demonstrates promise in mitigating EAE effects, especially in terms of clinical disability and demyelination. These results suggest AMPA-PAMs as potential targets of interest for MS treatment beyond immunomodulatory approaches.

• MeSH
• Allosteric Regulation MeSH
• Receptors, AMPA * metabolism   MeSH
• Demyelinating Diseases drug therapy   metabolism   MeSH
• Encephalomyelitis, Autoimmune, Experimental * drug therapy   metabolism   immunology   MeSH
• Fingolimod Hydrochloride pharmacology   therapeutic use   MeSH
• Disease Models, Animal MeSH
• Mice, Inbred C57BL * MeSH
• Mice MeSH
• Multiple Sclerosis * drug therapy   metabolism   immunology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Background: Multiple sclerosis (MS) pathology is characterized by acute and chronic inflammation, demyelination, axonal injury, and neurodegeneration. After decades of research into MS-related degeneration, recent efforts have shifted toward recovery and the prevention of further damage. A key area of focus is the remyelination process, where researchers are studying the effects of pharmacotherapy on myelin repair mechanisms. Multiple compounds are being tested for their potential to foster remyelination in different clinical settings through the application of less or more complex techniques to assess their efficacy. Objective: To review current methods and biomarkers to track myelin regeneration and recovery over time in people with MS (PwMS), with potential implications for promyelinating drug testing. Methods: Narrative review, based on a selection of PubMed articles discussing techniques to measure in vivo myelin repair and functional recovery in PwMS. Results: Non-invasive tools, such as structural Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), are being implemented to track myelin repair, while other techniques like evoked potentials, functional MRI, and digital markers allow the assessment of functional recovery. These methods, alone or in combination, have been employed to obtain precise biomarkers of remyelination and recovery in various clinical trials on MS. Conclusions: Combining different techniques to identify myelin restoration in MS could yield novel biomarkers, enhancing the accuracy of clinical trial outcomes for remyelinating therapies in PwMS.

• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Tick-borne encephalitis (TBE) is the most common tick-borne viral infection in Eurasia. Outcomes range from asymptomatic infection to fatal encephalitis, with host genetics likely playing a role. BALB/c mice have intermediate susceptibility to TBE virus (TBEV) and STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, which carries 12.5% of the STS genome on the BALB/c background, is more susceptible than BALB/c mice. In the present study, we employed these genetically distinct mouse models to investigate the host response to TBEV infection in both peripheral macrophages, one of the initial target cell populations, and the brain, the terminal target organ of the virus. METHODS: TBEV growth and the production of key cytokines and chemokines were measured and compared in macrophages derived from BALB/c, CcS-11, and STS mice. In addition, brains from these TBEV-infected mouse strains underwent in-depth transcriptomic analysis. RESULTS: Virus production in BALB/c and CcS-11 macrophages exhibited similar kinetics 24 and 48 h post-infection (hpi), but CcS-11 macrophages yielded significantly higher titers 72 hpi. Macrophages from both sensitive strains demonstrated elevated chemokine and proinflammatory cytokine production upon infection, whereas the resistant strain, STS, showed no cytokine/chemokine activation. Transcriptomic analysis of brain tissue demonstrated that the genetic background of the mouse strains dictated their transcriptional response to infection. The resistant strain exhibited a more robust cell-mediated immune response, whereas both sensitive strains showed a less effective cell-mediated response but increased cytokine signaling and signs of demyelination, with loss of oligodendrocytes. CONCLUSIONS: Our findings suggest that variations in susceptibility linked to host genetic background correspond with distinct host responses, both in the periphery upon virus entry into the organism and in the brain, the target organ of the virus. These results provide insights into the influence of host genetics on the clinical trajectory of TBE.

• MeSH
• Cytokines * metabolism   genetics   MeSH
• Genotype MeSH
• Encephalitis, Tick-Borne * immunology   virology   genetics   MeSH
• Macrophages * immunology   virology   MeSH
• Brain * virology   immunology   MeSH
• Mice, Inbred BALB C * MeSH
• Mice MeSH
• Encephalitis Viruses, Tick-Borne * genetics   physiology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Tato kazuistika popisuje léčbu pacienta s relabující-remitující formou roztroušené sklerózy (RR-RS), který zároveň trpí Crohnovou nemocí. Po počáteční terapii glatiramer-acetátem a interferonem beta-1a došlo u pacienta k pokračující aktivitě onemocnění, která si vyžádala změnu léčby. S ohledem na potřebu vysoce účinné terapie a pacientovu preferenci méně častých návštěv zdravotnického zařízení byla v dubnu 2022 zahájena léčba ponesimodem. Po více než dvouleté léčbě pacient zůstává klinicky stabilní, bez nových atak či progrese nemoci, a Crohnova nemoc je v remisi. Pacient dobře toleruje léčbu a vede plnohodnotný život, což potvrzuje účinnost a bezpečnost ponesimodu jako vhodné volby pro pacienty s aktivní RS a komorbiditami.

This case report describes the treatment of a patient with relapsing-remitting multiple sclerosis (RR-RS) who also suffers from Crohn's disease. After initial therapy with glatiramer acetate and interferon beta-1a, the patient had ongoing disease activity that required a change in treatment. Considering the need for highly effective therapy and the patient's preference for less frequent visits to the medical facility, treatment with ponesimod was started in April 2022. After more than two years of treatment, the patient remains clinically stable, without new relapses or disease progression, and Crohn's disease is in remission. The patient tolerates the treatment well and leads a full life, which confirms the efficacy and safety of ponesimod as a suitable choice for patients with active MS and comorbidities.

• Keywords
• ponesimod,
• MeSH
• Crohn Disease diagnosis   drug therapy   MeSH
• Demyelinating Diseases diagnostic imaging   MeSH
• Adult MeSH
• Quality of Life MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Disease Progression MeSH
• Sphingosine-1-Phosphate Receptors * antagonists & inhibitors   therapeutic use   MeSH
• Multiple Sclerosis, Relapsing-Remitting * diagnosis   drug therapy   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH