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
Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats. MXP rapidly crossed the blood-brain barrier, reaching peak median concentrations in both serum and brain 30 min post-administration, followed by an elimination phase with a half-life of 2.15 h. Locomotor activity in the open field test displayed a dose-response effect at low to moderate doses (10-20 mg/kg MXP). At higher doses (40 mg/kg), locomotor activity decreased. All doses of MXP significantly disrupted prepulse inhibition and the effect was present during the onset of its action as well as 60 min after treatment. Additionally, MXP demonstrated moderate acute toxicity, with an estimated LD50 of 500 mg/kg when administered subcutaneously. In summary, MXP exhibited a profile similar to typical dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses, sedative effects at higher doses, and disrupting sensorimotor gating. The accumulation of MXP in brain tissue is likely to contribute to acute intoxication in humans, potentially leading to negative experiences. Our findings highlight the potentially dangerous effects of recreational MXP use and underscore the risks of inducing serious adverse health outcomes.
- MeSH
- Behavior, Animal drug effects MeSH
- Rats MeSH
- Lethal Dose 50 MeSH
- Brain drug effects metabolism MeSH
- Piperidines pharmacokinetics pharmacology MeSH
- Motor Activity drug effects MeSH
- Rats, Wistar * MeSH
- Prepulse Inhibition drug effects MeSH
- Open Field Test drug effects MeSH
- Dose-Response Relationship, Drug * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Neurons in the CNS lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonizes PI3K signaling by hydrolyzing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3. This study explores whether increased PIP3 generation can promote long-distance regeneration in adults. We used a hyperactive PI3K, PI3Kδ (PIK3CD), to boost PIP3 levels in mature cortical neurons and assessed CST regeneration after SCI. Adult rats received AAV1-PIK3CD and AAV1-eGFP, or AAV1-eGFP alone, in the sensorimotor cortex concurrent with a C4 dorsal SCI. Transduced neurons showed increased pS6 levels, indicating elevated PI3K/Akt/mTOR signaling. CST regeneration, confirmed with retrograde tracing, was evaluated up to 16 weeks post injury. At 12 weeks, ∼100 axons were present at lesion sites, doubling to 200 by 16 weeks, with regeneration indices of 0.1 and 0.2, respectively. Behavioral tests showed significant improvements in paw reaching, grip strength, and ladder-rung walking in PIK3CD-treated rats, corroborated by electrophysiological recordings of cord dorsum potentials and distal flexor muscle electromyography. Thus, PI3Kδ upregulation in adult cortical neurons enhances axonal regeneration and functional recovery post SCI.
- MeSH
- Axons metabolism physiology MeSH
- Dependovirus genetics MeSH
- Class I Phosphatidylinositol 3-Kinases metabolism genetics MeSH
- Phosphatidylinositol 3-Kinases metabolism MeSH
- Genetic Vectors genetics MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Neurons metabolism MeSH
- Recovery of Function MeSH
- Spinal Cord Injuries * metabolism therapy genetics MeSH
- Pyramidal Tracts * metabolism MeSH
- Nerve Regeneration * MeSH
- Signal Transduction MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The research on possible cerebral involvement in Crohn's disease (CD) has been largely marginalized and failed to capitalize on recent developments in magnetic resonance imaging (MRI). OBJECTIVE: This cross-sectional pilot study searches for eventual macrostructural and microstructural brain affection in CD in remission and early after the disease onset. METHODS: 14 paediatric CD patients and 14 healthy controls underwent structural, diffusion weighted imaging and quantitative relaxation metrics acquisition, both conventional free precession and adiabatic rotating frame transverse and longitudinal relaxation time constants as markers of myelination, iron content and cellular loss. RESULTS: While no inter-group differences in cortical thickness and relaxation metrics were found, lower mean diffusivity and higher intracellular volume fraction were detected in CD patients over vast cortical regions essential for the regulation of the autonomous nervous system, sensorimotor processing, cognition and behavior, pointing to wide-spread cytotoxic oedema in the absence of demyelination, iron deposition or atrophy. CONCLUSION: Although still requiring further validation in longitudinal projects enrolling larger numbers of subjects, this study provides an indication of wide-spread cortical oedema in CD patients very early after the disease onset and sets possible directions for further research.
- Publication type
- Journal Article MeSH
Pochopení vztahu mezi senzomotorickými proměnnými a exerkiny, které ovlivňují funkci mozku a kognici, nám umožňuje hlouběji porozumět biologickému procesu stárnutí. Hlavním cílem této studie bylo zjistit, jak silně jsou mozkový neurotrofický faktor (brain-derived neurotrophic factor, BDNF), irisin, svalová hmota a svalová síla asociovány s výsledky testů vybraných kognitivních funkcí u starších žen a jak dobře je predikují. Padesát sedm starších žen (průměrný věk 70,4 ± 4,1 roku) absolvovalo baterii neuropsychologických testů, měření izometrické dynamometrie a bioelektrické impedance. Hladiny v krevním séru sledovaných exerkinů byly stanoveny enzymatickým imunosorbentním testem (ELISA). Pro testování predikcí byly využity hierarchické vícenásobné regresní modely. Odhadli jsme, že rozptyl 46,1 % v krátkodobé paměti byl zapříčiněn hladinami BDNF v séru, přičemž druhým statisticky významným prediktorem byl věk (beta = –0,22; p = 0,030). Síla dolních končetin (lower limb strength, LLS) prokázala významnou prediktivní sílu jak u paměti – bezprostřední vybavení (beta = 0,39; p = 0,004), tak u paměti – oddálené vybavení (beta = 0,45; p = 0,001). Hladiny BDNF v séru byly významným prediktorem u oddáleného vybavení (beta = 0,29; p = 0,048). Přidání hladin BDNF do modelu prokázalo významné zvýšení jeho prediktivní síly o přibližně 5,6 % (p = 0,048) u paměti – oddálené vybavení. Index kosterní svalové hmoty (skeletal muscle index, SMI) a úroveň vzdělání byly významnými prediktory mentální flexibility. Byla zjištěna silná pozitivní asociace mezi hladinami BDNF, irisinem, svalovou silou a kognitivní funkcí, přičemž irisin a svalová síla jsou silnými prediktory hladin BDNF u starších žen. Studie byla realizována s podporou grantu Univerzity Karlovy – PRIMUS/19/HUM/012, Specifického vysokoškolského výzkumu SVV 260599, projektu COOPERATIO a Grantové agentury UK číslo grantu 268321. Korespondenční adresa: PhDr. Veronika Holá Katedra gymnastiky a úpolových sportů FTVS UK José Martího 269/31 162 52 Praha 6-Veleslavín e-mail: veronika.hola@ftvs.cuni.cz
Understanding the relationship between sensorimotor variables and exerkines related to brain function and cognition may help better understand biological ageing. The main aim of this study was to determine how strongly brain-derived neurotrophic factor (BDNF), irisin, muscle mass and muscle strength are associated and predict scores on selected cognitive domain tests in older women. Fifty seven older women (mean age 70.4 ± 4.1 years) underwent a battery of cognitive and psychological tests and measurements of isometric dynamometry and bioelectrical impedance. Serum exerkines levels were measured by enzyme-linked immunosorbent assay (ELISA). Hierarchical multiple regression models were used to test the predictions. We estimated that 46.1% of the variance in short-term memory was accounted for by serum BDNF levels, with age being the second statistically significant predictor (Beta = -0.22; p = 0.030). Lower limb strength (LLS) showed significant predictive power in both immediate (Beta = 0.39; p = 0.004) and delayed memory (Beta = 0.45; p = 0.001), serum BDNF levels were a significant predictor in delayed memory (Beta = 0.29; p = 0.048). Adding serum BDNF levels to the model showed a significant increase in predictive power of approximately 5.6% (p = 0.048) in delayed memory. Skeletal muscle index (SMI) and education level were significant predictors of mental flexibility. A strong positive association between BDNF levels, irisin, muscle strength, and cognitive function was found, with irisin and muscle strength being strong predictors of BDNF levels in older women.
- Keywords
- irisin,
- MeSH
- Fibronectin Type III Domain physiology MeSH
- Cognition physiology MeSH
- Cognitive Aging * physiology MeSH
- Humans MeSH
- Brain-Derived Neurotrophic Factor blood MeSH
- Neuropsychological Tests * statistics & numerical data MeSH
- Memory physiology MeSH
- Prognosis MeSH
- Cross-Sectional Studies MeSH
- Regression Analysis MeSH
- Aged MeSH
- Muscular Atrophy etiology MeSH
- Muscle Strength physiology MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: The recovery of autonomic functions and the ability to reproduce in particular is of the highest priority to individuals with spinal cord injury (SCI). The potential of epidural spinal cord stimulation (ESCS) for promoting recovery of sensorimotor functions in the chronic phase of SCI has long been studied. In recent years, several studies have emerged confirming the positive effect of ESCS also on the cardiovascular system and neurogenic bladder and bowel. However, the potential of ESCS in restoring sexual function, especially ejaculation, has not yet been addressed. CASE REPORT: Two cases of people with chronic sensorimotor complete SCI in the 4th thoracic spinal segment are presented. Both men were also diagnosed with severe erectile dysfunction and anejaculation. Thanks to ESCS, Participant 1 successfully restored the ejaculatory reflex using PVS in his home environment. His outcome was subsequently verified under clinical conditions. During ESCS, Participant 1 was also able to achieve ejaculation by masturbation; moreover, he conceived a child naturally without the need for IVF. In Participant 2, we then demonstrated the same effect of ESCS on the restoration of the ejaculatory reflex when targeting the stimulation to the same spinal segment. CONCLUSION: This is the first report on the potential of ESCS for restoring the ability to ejaculate in individuals with complete SCI. Confirmation of these results could significantly reduce the need for assisted reproduction and improve the quality of life of men after SCI in the future.
- MeSH
- Adult MeSH
- Ejaculation * physiology MeSH
- Epidural Space MeSH
- Erectile Dysfunction etiology therapy physiopathology MeSH
- Thoracic Vertebrae MeSH
- Humans MeSH
- Spinal Cord Stimulation * methods MeSH
- Spinal Cord Injuries * complications physiopathology therapy rehabilitation MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Brain imaging studies in complex regional pain syndrome (CRPS) have found mixed evidence for functional and structural changes in CRPS. In this cross-sectional study, we evaluated two patient cohorts from different centers and examined functional connectivity (rsFC) in 51 CRPS patients and 50 matched controls. rsFC was compared in predefined ROI pairs, but also in non-hypothesis driven analyses. Resting state (rs)fMRI changes in default mode network (DMN) and the degree rank order disruption index (kD) were additionally evaluated. Finally, imaging parameters were correlated with clinical severity and somatosensory function. Among predefined pairs, we found only weakly to moderately lower functional connectivity between the right nucleus accumbens and bilateral ventromedial prefrontal cortex in the infra-slow oscillations (ISO) band. The unconstrained ROI-to-ROI analysis revealed lower rsFC between the periaqueductal gray matter (PAG) and left anterior insula, and higher rsFC between the right sensorimotor thalamus and nucleus accumbens. In the correlation analysis, pain was positively associated with insulo-prefrontal rsFC, whereas sensorimotor thalamo-cortical rsFC was positively associated with tactile spatial resolution of the affected side. In contrast to previous reports, we found no group differences for kD or rsFC in the DMN, but detected overall lower data quality in patients. In summary, while some of the previous results were not replicated despite the larger sample size, novel findings from two independent cohorts point to potential down-regulated antinociceptive modulation by the PAG and increased connectivity within the reward system as pathophysiological mechanisms in CRPS. However, in light of the detected systematic differences in data quality between patients and healthy subjects, validity of rsFC abnormalities in CRPS should be carefully scrutinized in future replication studies.
- MeSH
- Default Mode Network diagnostic imaging physiopathology MeSH
- Adult MeSH
- Complex Regional Pain Syndromes * physiopathology diagnostic imaging MeSH
- Connectome methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Brain physiopathology diagnostic imaging MeSH
- Nerve Net physiopathology diagnostic imaging MeSH
- Cross-Sectional Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
BACKGROUND AND OBJECTIVES: The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. METHODS: Pre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population - Dementia Rating Scale 2. RESULTS: PD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. CONCLUSIONS: Our findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.
- MeSH
- Deep Brain Stimulation * adverse effects MeSH
- Cognitive Dysfunction * etiology diagnostic imaging physiopathology pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Neuropsychological Tests MeSH
- Subthalamic Nucleus * diagnostic imaging MeSH
- Parkinson Disease * therapy diagnostic imaging pathology MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
In Parkinson's disease (PD), impaired gait and cognition affect daily activities, particularly in the more advanced stages of the disease. This study investigated the relationship between gait parameters, cognitive performance, and brain morphology in patients with early untreated PD. 64 drug-naive PD patients and 47 healthy controls (HC) participated in the study. Single- and dual-task gait (counting task) were examined using an expanded Timed Up & Go Test measured on a GaitRite walkway. Measurements included gait speed, stride length, and cadence. A brain morphometry analysis was performed on T1-weighted magnetic resonance (MR) images. In PD patients compared to HC, gait analysis revealed reduced speed (p < 0.001) and stride length (p < 0.001) in single-task gait, as well as greater dual-task cost (DTC) for speed (p = 0.007), stride length (p = 0.014) and cadence (p = 0.029). Based on the DTC measures in HC, PD patients were further divided into two subgroups with normal DTC (PD-nDTC) and abnormally increased DTC (PD-iDTC). For PD-nDTC, voxel-based morphometric correlation analysis revealed a positive correlation between a cluster in the left primary motor cortex and stride-length DTC (r = 0.57, p = 0.027). For PD-iDTC, a negative correlation was found between a cluster in the right lingual gyrus and the DTC for gait cadence (r=-0.35, pFWE = 0.018). No significant correlations were found in HC. The associations found between brain morphometry and gait performance with a concurrent cognitive task may represent the substrate for gait and cognitive impairment occurring since the early stages of PD.
- MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Brain * diagnostic imaging pathology physiopathology MeSH
- Gait Disorders, Neurologic * etiology physiopathology diagnostic imaging pathology MeSH
- Neuropsychological Tests MeSH
- Parkinson Disease * diagnostic imaging physiopathology pathology complications MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: There is growing evidence for the effectiveness of mirror therapy (MT) on pain reduction in patients with type I complex regional pain syndrome (CRPS I). AIM: To evaluate the efficacy of MT on pain reduction and hand function in subjects with unilateral upper extremity CRPS I. DESIGN: Randomized controlled trial with control group cross-over (half cross-over design). SETTING: Subjects with CRPS I were outpatients of a university hospital and cooperating centers. All patients carried out the daily exercise at home. POPULATION: Subjects with unilateral upper extremity CRPS I meeting the Budapest diagnostic criteria. METHODS: Subjects were randomly divided into two groups. Group A (N.=13) carried out a ten-minute MT exercise daily, for a total duration of six weeks. Group B (N.=14) acted as a control group for six weeks followed by six weeks of MT with the same characteristics as Group A. Upper extremity active range of motion, strength, dexterity, limb volume, affected-to-unaffected hand temperature difference, and health-related quality of life were evaluated before and after each period. Daily records on the visual analogue scale were used for pain evaluation. Effectiveness was calculated using mixed-effects modelling for between-group comparisons and within-group variability, and identification of significant predictors. RESULTS: Twenty-three females and four males with an average age of 56.1±9.6 years completed the study. Except for the affected-to-unaffected hand temperature difference, both groups consistently demonstrated significant or near-significant improvements in measured parameters after MT period. The improvements were evident upon an intergroup comparison of Group A and the control period of Group B as well as longitudinally within Group B. No significant improvement was found during the control period. CONCLUSIONS: Principles focused on mirror visual feedback to the central nervous system can sustain promising therapeutic potential as part of the treatment for pain reduction and hand function in CRPS I patients. CLINICAL REHABILITATION IMPACT: MT can be considered as part of the therapeutic regimen employed for the treatment of CRPS I.
- MeSH
- Pain MeSH
- Upper Extremity MeSH
- Complex Regional Pain Syndromes * therapy MeSH
- Quality of Life MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Feedback, Sensory MeSH
- Reflex Sympathetic Dystrophy * therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH