BACKGROUND AND AIMS: Neurodegenerative disorders affecting the brain and spinal cord are caused by a large number of factors. More recently, imbalances in gut microbiota are found to be one factor linked directly to neurological dysfunction. Probiotics prevent cognitive decline. For the first time, the effect of probiotics was assessed by monitoring the concentrations of the neurodegeneration biomarker neurofilament light chains (NfL) in a well-defined group of community-dwelling individuals. The aim of this study was to determine whether administration of our new probiotics could reduce NfL concentrations. METHODS: The serum NfL concentrations were measured in total of 190 serum samples of 85 older community-dwelling individuals. The participants were randomly divided into two groups: the PROPLA group and the PLAPRO group. Individuals in the PROPLA group started with a three-month use of probiotics and continued with a three-month use of placebo while the order was reversed in the PLAPRO group. The participants underwent detailed examinations at three time points: at baseline, in three and six months. The serum NfL concentrations were determined using ultrasensitive single-molecule array (SIMOA) assay. RESULTS: Longitudinal comparisons of NfL concentrations between samplings at different time points in the PROPLA and PLAPRO groups showed no statistically significant differences. Baseline NfL concentrations at the beginning of the study and in the succeeding samplings were not significantly different for the two groups in cross-sectional comparisons. CONCLUSIONS: Serum NfL concentrations were not influenced by the three-month use of probiotics.
- MeSH
- Biomarkers blood MeSH
- Double-Blind Method MeSH
- Middle Aged MeSH
- Humans MeSH
- Neurofilament Proteins * blood MeSH
- Probiotics * therapeutic use MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Gastrointestinal Microbiome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Úvod: Telerehabilitace se zdá být velmi nadějnou alternativou k běžné rehabilitační péči a mohla by být přínosná i u osob s neurologickým onemocněním. Cíl: Cílem studie bylo zmapovat dosavadní publikovanou evidenci v oblasti telerehabilitace u dospělých osob se získaným neurologickým onemocněním. Metodika: V rámci systematické rešerše byly vyhledány dostupné klinické studie publikované na téma telerehabilitace u osob s neurologickým onemocněním v období 2010–2023. Vyhledávání probíhalo pomocí zvolené kombinace klíčových slov (telerehabilitation, telemonitoring, telemedicine, teleneurology, neurorehabilitation, multiple sclerosis, stroke, Parkinson‘s disease, neurological disorders). Kritéria pro zařazení splňovaly studie publikované v anglickém jazyce a s účastníky mladšími 18 let. Vyřazeny byly studie zaměřující se pouze na telemonitoring bez rehabilitační intervence. Pro účely vyhodnocení kvality studií byla využita škála PEDro (1–11). Na základě této hodnoticí škály byly vyřazeny studie nižší kvality (< 4) a následně podrobně analyzovány studie vyšší kvality. Výsledky: Celkem bylo nalezeno 190 studií. Po odstranění duplikací a studií, které nesplňovaly podmínky (nebyly zaměřeny na dospělé pacienty, byly pouze rešeršemi nebo nebyl dostupný full-text) zůstalo do analýzy 111 studií. Z toho 49 se týkalo telerehabilitace u roztroušené sklerózy, 41 po cévní mozkové příhodě, 16 u Parkinsonovy choroby, 4 telerehabilitace u poruch řeči a 8 dalších u jiných diagnóz (4 kraniotraumata, 2 poranění míchy, 1 amyotrofická laterální skleróza a 1 demence). Mezi intervence poskytované formou telerehabilitace se řadil nejčastěji kognitivní trénink, dále terapie zaměřená na horní končetinu, kombinovaný trénink, trénink chůze nebo také terapie únavy. Závěr: Z výsledků je patrné, že intervence poskytované prostřednictvím telerehabilitace jsou velmi rozmanité a mohou přinášet výsledky v některých případech srovnatelné s běžnou rehabilitací. Zdá se, že telerehabilitace je nejlépe využitelná u osob s roztroušenou sklerózou a cévní mozkovou příhodou.
Introduction: Telerehabilitation seems to be a very promising alternative to conventional rehabilitation care and could also be beneficial for people with neurological diseases. Aim: The aim of the study was to map the existing published evidence in the field of telerehabilitation in adults with acquired neurological disease. Methods: A systematic search was conducted to identify available clinical studies published on telerehabilitation in people with neurological disease between 2010 and 2023 using a selected combination of keywords (telerehabilitation, telemonitoring, telemedicine, teleneurology, neurorehabilitation, multiple sclerosis, stroke, Parkinson’s disease, neurological disorders). Studies published in English and with participants under 18 years of age met the inclusion criteria. Studies focusing only on telemonitoring without rehabilitation intervention were excluded. The PEDro scale (1–11) was used to assess the quality of the studies. Based on this rating scale, studies of lower quality (< 4) were excluded, and then higher quality studies were analyzed in detail. Results: A total of 190 studies were identified. After removing duplicates and studies that did not meet the eligibility criteria (not focused on adult patients, were searches only, or full-text was not available), 111 studies remained for analysis. Of these, 49 were related to telerehabilitation for multiple sclerosis, 41 for stroke, 16 for Parkinson’s disease, 4 to telerehabilitation for speech disorders, and 8 for other diagnoses (4 craniotraumas, 2 spinal cord injuries, 1 amyotrophic lateral sclerosis, and 1 dementia). Interventions provided through telerehabilitation included most commonly cognitive training, then upper limb-focused therapy, combined training, gait training, or fatigue therapy. Conclusion: The results show that the interventions provided through telerehabilitation are very diverse and can produce results in some cases comparable to conventional rehabilitation. Telerehabilitation seems to be most useful for people with multiple sclerosis and stroke.
- MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Meta-Analysis as Topic MeSH
- Nervous System Diseases rehabilitation MeSH
- Parkinson Disease rehabilitation MeSH
- Stroke Rehabilitation methods MeSH
- Multiple Sclerosis rehabilitation MeSH
- Telerehabilitation * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Radiologicky izolovaný syndrom je definován jako náhodně zjištěný obraz na magnetické rezonanci typický pro roztroušenou sklerózu u pacienta, který nemá žádné klinické příznaky pro toto onemocnění. Tento termín byl poprvé použit včetně definice kritérií v roce 2009. Cílem nových revidovaných kritérií radiologicky izolovaného syndromu z roku 2023 je zajistit přesnou a rychlejší diagnostiku, než umožňovala původní kritéria z roku 2009. Nová kritéria vyžadují alespoň jedno T2 hypersignální ložisko v jedné ze čtyř typických lokalizací pro roztroušenou sklerózu spolu se dvěma z následujících tří znaků: míšní léze, oligoklonální pásy omezené na mozkomíšní mok nebo nové T2 hypersignální ložisko nebo po podání kontrastní látky zvýrazňující se ložisko pozorované na následném vyšetření magnetickou rezonancí. V diagnostice radiologicky izolovaného syndromu se stanovují rizikové faktory pro konverzi do klinicky definitivní roztroušené sklerózy a hrozícího těžšího průběhu onemocnění. Jedná se o nižší věk pacienta, lokalizaci ložisek (infratentoriálně a intramedulárně) a přítomnost oligoklonálních pásů v mozkomíšním moku nepřítomných v séru. To je důležité pro zvážení léčebné intervence. Nedávné klinické studie ukázaly, že perorální léčba modifikující průběh onemocnění může u pacientů s radiologicky izolovaným syndromem oddálit první klinickou příhodu nebo jí zabránit. Tento posun diagnostiky a zvažování léčby již v preklinickém stadiu vytváří enormní tlak na precizní diagnostiku a management, aby tito náhodně vytypovaní pacienti byli směřováni do RS center, kde budou dále podrobně vyšetřeni. Revidovaná McDonaldova diagnostická kritéria pro roztroušenou sklerózu z roku 2024 budou klasifikovat osoby s pozitivními dalšími markery z mozkomíšního moku a pokročilými MR biomarkery jako osoby s preklinickou RS, což zdůrazňuje důležitost preciznosti v diagnostice a edukaci jak radiologů, tak neurologů, jakým způsobem postupovat, aby se pacient dostal včas do sledování v centrech vysoce specializované péče pro pacienty s roztroušenou sklerózou.
Radiologically isolated syndrome (RIS) is defined as an incidental finding on magnetic resonance imaging (MRI) that is typical of multiple sclerosis (MS) in a patient without clinical symptoms of the disease. This term, along with its definition criteria, was first introduced in 2009. The newly revised 2023 RIS criteria aim to provide a more accurate and faster diagnosis compared to the original 2009 criteria. These criteria require at least one T2-hyperintense lesion in one of the four typical locations for MS, along with two of the following three features: spinal cord lesions, oligoclonal bands confined to the cerebrospinal fluid (but absent in the serum), or a new T2-hyperintense lesion (or, after contrast administration, a prominent lesion visible on follow-up MRI scans). An MRI diagnosis of RIS establishes a risk factor for conversion to clinically definite MS and a more severe disease course. These risk factors include the patient’s age, the location of the lesions (infratentorial and intramedullary) and the presence of oligoclonal bands in the cerebrospinal fluid. These factors are critical when considering therapeutic interventions. Recent clinical trials have demonstrated that oral disease-modifying therapies can delay or prevent the first clinical event in patients with RIS. This shift in diagnosis and treatment considerations to preclinical stages places enormous pressure on ensuring precise diagnosis and management. It is essential that such patients are referred to MS centers for further specialized investigations. The forthcoming Revised McDonald Criteria of 2024 will classify individuals with additional cerebrospinal fluid markers and advanced MRI biomarkers as having preclinical MS. This highlights the importance of precise diagnosis and the need for radiologists and neurologists to familiarize themselves with the appropri- ate steps to ensure patients are monitored at highly specialized MS care centers.
BACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.
- MeSH
- Dysbiosis metabolism MeSH
- Blood-Brain Barrier metabolism MeSH
- Humans MeSH
- Brain * metabolism MeSH
- Neurodegenerative Diseases * microbiology metabolism MeSH
- Brain-Gut Axis * physiology MeSH
- Probiotics MeSH
- Aging * MeSH
- Gastrointestinal Microbiome * physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Obezita a diabetes mellitus 2. typu (DM2T) sú významnými rizikovými faktormi rozvoja kognitívnej dysfunkcie a neurodegeneratívnych ochorení. Ich spoločný patofyziologický základ zahŕňa inzulínovú rezistenciu, chronický subklinický systémový zápal a neurozápal, poruchy mikrobiómu, hormonálnu dysreguláciu a štrukturálne zmeny mozgu. Tieto faktory vedú k zhoršeniu pamäte, exekutívnych funkcií a k akcelerácii neurodegenerácie. Pozitívne účinky úpravy životného štýlu – vrátane zníženia telesnej hmotnosti, zvýšenia fyzickej aktivity a úpravy výživy a stravovacích návykov – sa prejavujú zlepšením inzulínovej senzitivity v mozgu, zvýšením neurotrofických faktorov, redukciou systémového zápalu a neurozápalu a zlepšením metabolizmu. Kombinácia behaviorálnych a farmakologických intervencií môže spomaliť kognitívny pokles a znížiť riziko demencie u populácie s obezitou a poruchou metabolizmu glukózy.
Obesity and type 2 diabetes (T2D) are important risk factors for the development of cognitive dysfunction and neurodegenerative diseases. Their common pathophysiological substrate includes insulin resistance, chronic subclinical systemic inflammation, neuroinflammation, shifts in the intestinal microbiome composition, hormonal dysregulation, and structural changes of the brain. These factors lead to impaired memory, executive functions, and accelerated neurodegeneration. The positive effects of lifestyle modifications — including weight loss, increased physical activity, and improved dietary composition — are manifested by improved insulin sensitivity in the brain, increased neurotrophic factors, reduced systemic inflammation and neuroinflammation, and improved metabolism. A combination of behavioral and pharmacological interventions may slow cognitive decline and reduce the risk of dementia in patients with obesity, prediabetes and T2D.
- MeSH
- Exercise MeSH
- Diabetes Mellitus, Type 2 complications MeSH
- Weight Loss MeSH
- Cognition Disorders * etiology MeSH
- Humans MeSH
- Neurodegenerative Diseases etiology MeSH
- Obesity * complications MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Spinal cord injury (SCI) results in paralysis, driven partly by widespread glutamate-induced secondary excitotoxic neuronal cell death in and around the injury site. While there is no curative treatment, the standard of care often requires interventive decompression surgery and repair of the damaged dura mater close to the injury locus using dural substitutes. Such intervention provides an opportunity for early and local delivery of therapeutics directly to the injured cord via a drug-loaded synthetic dural substitute for localized pharmacological therapy. Riluzole, a glutamate-release inhibitor, has shown neuroprotective potential in patients with traumatic SCI, and therefore, this study aimed to develop an electrospun riluzole-loaded synthetic dural substitute patch suitable for the treatment of glutamate-induced injury in neurons. A glutamate-induced excitotoxicity was optimized in SH-SY5Y cells by exploring the effect of glutamate concentration and exposure duration. The most effective timing for administering riluzole was found to be at the onset of glutamate release as this helped to limit extended periods of glutamate-induced excitotoxic cell death. Riluzole-loaded patches were prepared by using blend electrospinning. Physicochemical characterization of the patches showed the successful encapsulation of riluzole within polycaprolactone fibers. A drug release study showed an initial burst release of riluzole within the first 24 h, followed by a sustained release of the drug over 52 days to up to approximately 400 μg released for the highest loading of riluzole within fiber patches. Finally, riluzole eluted from electrospun fibers remained pharmacologically active and was capable of counteracting glutamate-induced excitotoxicity in SH-SY5Y cells, suggesting the clinical potential of riluzole-loaded dural substitutes in counteracting the effects of secondary injury in the injured spinal cord.
- MeSH
- Drug Implants MeSH
- Glutamic Acid metabolism MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neurons drug effects MeSH
- Neuroprotective Agents * administration & dosage chemistry pharmacology MeSH
- Polyesters chemistry MeSH
- Spinal Cord Injuries * drug therapy MeSH
- Riluzole * administration & dosage chemistry pharmacology MeSH
- Drug Liberation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Full recovery from spinal cord injury requires axon regeneration to re-establish motor and sensory pathways. In mammals, the failure of sensory and motor axon regeneration has many causes intrinsic and extrinsic to neurons, amongst which is the lack of adhesion molecules needed to interact with the damaged spinal cord. This study addressed this limitation by expressing the integrin adhesion molecule α9, along with its activator kindlin-1, in sensory neurons via adeno-associated viral (AAV) vectors. This enabled sensory axons to regenerate through spinal cord injuries and extend to the brainstem, restoring sensory pathways, touch sensation and sensory behaviours. One of the integrin ligands in the injured spinal cord is tenascin-C, which serves as a substrate for α9β1 integrin, a key receptor in developmental axon guidance. However, the adult PNS and CNS neurons lack this receptor. Sensory neurons were transduced with α9 integrin (which pairs with endogenous β1 to form a α9β1 tenascin receptor) together with the integrin activator kindlin-1. Regeneration from sensory neurons transduced with α9integrin and kindlin-1 was examined after C4 and after T10 dorsal column lesions with C6,7 and L4,5 sensory ganglia injected with AAV1 vectors. In animals treated with α9 integrin and kindlin-1, sensory axons regenerated through tenascin-C-expressing connective tissue strands and bridges across the lesions and then re-entered the CNS tissue. Many axons regenerated rostrally to the level of the medulla. Axons grew through the dorsal grey matter rather than their normal pathway the dorsal columns. Growth was slow, axons taking 12 weeks to grow from T10 to the medulla, a distance of 4-5 cm. Functional recovery was confirmed through cFos activation in neurons rostral to the injury after nerve stimulation and VGLUT1/2 staining indicating new synapse formation above the lesion. Behavioural recovery was seen in both heat and mechanical sensation, as well as tape removal tests. This approach demonstrates the potential of integrin-based therapies for long distance sensory axon regeneration and functional recovery following thoracic and partial recovery after cervical spinal cord injury.
- MeSH
- Axons MeSH
- Dependovirus genetics MeSH
- Genetic Vectors MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Sensory Receptor Cells * metabolism physiology pathology MeSH
- Recovery of Function physiology MeSH
- Spinal Cord Injuries * pathology physiopathology metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Nerve Tissue Proteins metabolism genetics MeSH
- Nerve Regeneration * physiology MeSH
- Tenascin metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, Non-P.H.S. 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
INTRODUCTION: Mitochondrial dysfunction stands as a pivotal feature in neurodegenerative disorders, spurring the quest for targeted therapeutic interventions. This review examines Ubiquitin-Specific Protease 30 (USP30) as a master regulator of mitophagy with therapeutic promise in Alzheimer's disease (AD) and Parkinson's disease (PD). USP30's orchestration of mitophagy pathways, encompassing PINK1-dependent and PINK1-independent mechanisms, forms the crux of this exploration. METHOD: A systematic literature search was conducted in PubMed, Scopus, and Web of Science, selecting studies that investigated USP's function, inhibitor design, or therapeutic efficacy in AD and PD. Inclusion criteria encompassed mechanistic and preclinical/clinical data, while irrelevant or duplicate references were excluded. Extracted findings were synthesized narratively. RESULTS: USP30 modulates interactions with translocase of outer mitochondrial membrane (TOM) 20, mitochondrial E3 ubiquitin protein ligase 1 (MUL1), and Parkin, thus harmonizing mitochondrial quality control. Emerging novel USP30 inhibitors, racemic phenylalanine derivatives, N-cyano pyrrolidine, and notably, benzosulphonamide class compounds, restore mitophagy, and reduce neurodegenerative phenotypes across diverse models with minimal off-target effects. Modulation of other USPs also influences neurodegenerative disease pathways, offering additional therapeutic avenues. CONCLUSIONS: In highlighting the nuanced regulation of mitophagy by USP30, this work heralds a shift toward more precise and effective treatments, paving the way for a new era in the clinical management of neurodegenerative disorders.
- MeSH
- Precision Medicine methods MeSH
- Humans MeSH
- Mitochondrial Proteins MeSH
- Mitophagy * physiology drug effects MeSH
- Neurodegenerative Diseases * drug therapy metabolism MeSH
- Ubiquitin-Specific Proteases metabolism antagonists & inhibitors MeSH
- Thiolester Hydrolases metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
