System Dysfunction In Patients Research Articles

Evaluation of the efficacy of complex analgesic therapy, including a combination of B vitamins, in patients with combination of osteoarthritis and chronic non-specific low back pain (results of an open-label pilot clinical trial)

The vitamin B1, B6 and B12 complex (VBC) is frequently used to treat acute and chronic low back pain.Objective: to investigate the effect of a combination of a non-steroidal anti-inflammatory drug (NSAID) and a VBC on the main manifestations of nociceptive system dysfunction in patients with combination of osteoarthritis (OA) and chronic non-specific low back pain (NSLBP).Material and methods. The study group consisted of 99 patients (82% women, mean age 63.6±17.2 years) with OA of various localization andNSLBP who had moderate to severe pain (≥4 on a numerical rating scale, NRS 0–10). All patients received etoricoxib 60 mg/day (up to 14 days) and a course of intramuscular (IM) injections of VBC (a drug for parenteral administration containing solutions of thiamine 100 mg, pyridoxine 100 mg, cyanocobalamin 1.0 mg and lidocaine 20 mg) 2.0 ml №10. Treatment outcome was assessed after 14 days.Results and discussion. During treatment, the vast majority of patients showed a significant improvement: the median severity of pain on movement (NRS) decreased from 6.3 [5.0; 8.0] to 3.7 [3.0; 5.0], p=0.0001; functional impairment  –  from 3.8 [2.0; 6.0] to 2.2 [1.0; 3.0], p=0.001; fatigue – from 5.6 [4.0; 8.0] to 3.5 [0.0; 2.0], p=0.0001. 71.6% of patients rated the treatment results as good or excellent. Six patients had adverse reactions: 2 – local pain at the site of the intramuscular injections, 1 – arterial hypertension, 3 – epigastric pain. No serious adverse events were recorded.Conclusion. The combined use of NSAIDs and VBC can provide significant improvement in patients with a combination of OA and NSLBP.

Immunomodulation through Nutrition Should Be a Key Trend in Type 2 Diabetes Treatment.

An organism's ability to function properly depends not solely on its diet but also on the intake of nutrients and non-nutritive bioactive compounds that exert immunomodulatory effects. This principle applies both to healthy individuals and, in particular, to those with concomitant chronic conditions, such as type 2 diabetes. However, the current food industry and the widespread use of highly processed foods often lead to nutritional deficiencies. Numerous studies have confirmed the occurrence of immune system dysfunction in patients with type 2 diabetes. This article elucidates the impact of specific nutrients on the immune system function, which maintains homeostasis of the organism, with a particular emphasis on type 2 diabetes. The role of macronutrients, micronutrients, vitamins, and selected substances, such as omega-3 fatty acids, coenzyme Q10, and alpha-lipoic acid, was taken into consideration, which outlined the minimum range of tests that ought to be performed on patients in order to either directly or indirectly determine the severity of malnutrition in this group of patients.

Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study.

This study aimed to investigate the extent of autonomic nervous system dysfunction in patients with chronic migraine using heart rate variability analysis. In addition, we explored the potential association between heart rate variability and treatment outcomes in patients receiving preventive treatment. In this cross-sectional and prospective study, we compared heart rate variability profiles in 81 preventive-naïve chronic migraine patients and 58 healthy controls. In addition, treatment responses of patients, who received a 12-week treatment with flunarizine, were assessed in relation to baseline heart rate variability. We observed that chronic migraine patients had a reduced heart rate variability, signifying autonomic dysfunction in comparison to healthy controls. Furthermore, patients presenting normal heart rate variability, characterized by a standard deviation exceeding 30 milliseconds in normal-to-normal RR intervals, experienced a superior response to flunarizine treatment. This improvement was exemplified by a significantly larger reduction in monthly headache days for patients with higher heart rate variability compared to those with lower heart rate variability: -9.7 (5.9) vs. -6.2 (6.0) days (p = .026). Autonomic dysfunction occurs in chronic migraine as evaluated by heart rate variability. A preserved function is associated with a better treatment outcome to flunarizine.Trial registration: Neurologic Signatures of Chronic Pain Disorders, NCT02747940. Registered 22 April 2016, https://clinicaltrials.gov/ct2/show/NCT02747940.

The asymmetry of glymphatic system dysfunction in patients with temporal lobe epilepsy: A DTI-ALPS study

Background and purposeWhile the occurrence of glymphatic system dysfunction has been observed in temporal lobe epilepsy (TLE), the potential asymmetry of this system has yet to be investigated in the TLE context. We aimed to investigate the glymphatic system function in both hemispheres and to analyze asymmetric features of the glymphatic system in TLE patients using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Materials and methods43 patients (left TLE (LTLE), n = 20; right TLE (RTLE), n = 23) and 39 healthy controls (HC) were enrolled in this study. The DTI-ALPS index was calculated for the left (left ALPS index) and right (right ALPS index) hemispheres respectively. An asymmetry index (AI) was calculated by AI = (Right − Left)/ [(Right + Left)/2] to represent the asymmetric pattern. Independent two sample t-test, two-sample paired t-test or one-way ANOVA with Bonferroni correction were conducted to compare the differences in ALPS indices and AI among the groups. ResultsBoth left ALPS index (p = 0.040) and right ALPS index (p = 0.001) of RTLE patients were significantly decreased, while only left ALPS index of LTLE patients (p = 0.005) was reduced. Compared to contralateral ALPS index, the ipsilateral ALPS index was significantly decreased in TLE (p = 0.008) and RTLE (p = 0.009) patients. Leftward asymmetry of the glymphatic system was found in HC (p = 0.045) and RTLE (p = 0.009) patients. The LTLE patients presented reduced asymmetric traits when compared to RTLE patients (p = 0.029). ConclusionThe TLE patients exhibited altered ALPS indices, which could be triggered by glymphatic system dysfunction. Altered ALPS indices were more severe in ipsilateral than in the contralateral hemisphere. Moreover, LTLE and RTLE patients exhibited different change patterns of the glymphatic system. In addition, glymphatic system function presented asymmetric patterns in both normal adult brain and RTLE patients.

Glymphatic system dysfunction in patients with occipital lobe epilepsy.

We aimed to investigate the glymphatic system function in patients with occipital lobe epilepsy (OLE) and healthy controls using diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. We retrospectively included 23 patients with OLE and 30 healthy controls. The participants underwent brain MRI, which was normal, and diffusion tensor imaging. We used the DSI Studio for data preprocessing, obtained the fiber orientation and diffusivities, and calculated the DTI-ALPS index from the diffusivity values associated with the projection and association fibers in the left hemisphere. There were no differences in mean age (31.6 years [range: 13-58] vs. 31.3 years [range: 20-57], p=.912) and male sex ratio (10/23 [43.5%] vs. 15/30 [50.0%]) between the groups. Compared to healthy controls, the diffusivities in patients with OLE were higher along the Y-axis in the projection fiber and along the Z-axis in the association fiber and lower along the Y-axis in the association fiber. The DTI-ALPS index in patients with OLE was lower than that in the healthy controls (1.421±0.171vs. 1.667±0.271, p<.001, 95% confidence interval of difference=0.117-0.376, Test statistic t=3.823). We found no association between the DTI-ALPS index and clinical characteristics in OLE. The DTI-ALPS index in patients with OLE was significantly lower than that in healthy controls, suggesting glymphatic system dysfunction in OLE. The DTI-ALPS index could help assess the glymphatic system function in patients with epilepsy.

The effect of lifestyle change on autonomic nervous system dysfunction in patients with metabolic syndrome

Study Design: A prospective clinical cohort study. Objective: In this study, it was aimed to examine the effects of metabolic syndrome, which affects many organs, on the autonomic nervous system and to observe the changes after treatment. Materials and Methods: Heart rate variability values of 101 metabolic syndrome patients who were treated at the Kocaeli University Cardiology Outpatient Clinic included in the study. All patients were offered lifestyle change suggestions in addition to their medical treatments. At the end of three months, the heart rate variability parameters of the patients were re-evaluated. Results: Heart rate variability values were found to be significantly lower in metabolic syndrome patients compared to the control group. It was observed that the heart rate variability values improved significantly in half of the patients who applied the given treatment with lifestyle changes. A decrease in heart rate change parameters was found in the group that did not implement lifestyle changes compared to the beginning of the study. Conclusions: Autonomic nervous system functions evaluated by heart rate variability decreased in patients with metabolic syndrome, and the treatment and lifestyle changes had a positive effect on these parameters.

Orexin/hypocretin system dysfunction in patients with Takotsubo syndrome: A novel pathophysiological explanation.

Takotsubo syndrome (TTS) is an acute heart failure syndrome. Emotional or physical stressors are believed to precipitate TTS, while the pathophysiological mechanism is not yet completely understood. During the coronavirus disease (COVID-19) pandemic, an increased incidence of TTS has been reported in some countries; however, the precise pathophysiological mechanism for developing TTS with acute COVID-19 infection is unknown. Nevertheless, observing the symptoms of COVID-19 might lead to new perspectives in understanding TTS pathophysiology, as some of the symptoms of the COVID-19 infection could be assessed in the context of an orexin/hypocretin-system dysfunction. Orexin/hypocretin is a cardiorespiratory neuromodulator that acts on two orexin receptors widely distributed in the brain and peripheral tissues. In COVID-19 patients, autoantibodies against one of these orexin receptors have been reported. Orexin-system dysfunction affects a variety of systems in an organism. Here, we review the influence of orexin-system dysfunction on the cardiovascular system to propose its connection with TTS. We propose that orexin-system dysfunction is a potential novel explanation for the pathophysiology of TTS due to direct or indirect dynamics of orexin signaling, which could influence cardiac contractility. This is in line with the conceptualization of TTS as a cardiovascular syndrome rather than merely a cardiac abnormality or cardiomyopathy. To the best of our knowledge, this is the first publication to present a plausible connection between TTS and orexin-system dysfunction. We hope that this novel hypothesis will inspire comprehensive studies regarding orexin's role in TTS pathophysiology. Furthermore, confirmation of this plausible pathophysiological mechanism could contribute to the development of orexin-based therapeutics in the treatment and prevention of TTS.

Glymphatic system dysfunction in patients with early chronic kidney disease.

IntroductionIt is a recent finding that glymphatic system dysfunction contributes to various neurological problems. The purpose of this research was to assess the function of the glymphatic system in neurologically asymptomatic early chronic kidney disease (CKD) patients and healthy controls, using diffusion tensor image analysis along perivascular space (DTI-ALPS) index.MethodsIn a prospective study, we included patients with early CKD who were asymptomatic for neurological issues and obtained clinical and laboratory data. In all participants, brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was conducted. We used DSI program for DTI preprocessing and DTI-ALPS index estimation. The DTI-ALPS index was compared between patients with early CKD and healthy controls, and the association between clinical characteristics and the DTI-ALPS index was investigated.ResultsEighteen patients with early CKD and 18 healthy controls were included in this study. Patients with early CKD had lower DTI-ALPS index than healthy controls (1.259 ± 0.199 vs. 1.477 ± 0.232, p = 0.004). In the correlation analysis, the DTI-ALPS index had no significant relationship with other clinical factors.ConclusionWe suggest dysfunction of glymphatic system in patients with early chronic kidney disease using the DTI-ALPS index. This may be related to the pathophysiology of neurological problems including impairment of cognition in patients with early CKD.

Nervous-mental stress and cognitive disorders as components of stress state in type 2 diabetic patients

The review focuses on the problem of nervous system dysfunction in patients with type 2 diabetes mellitus (DM), which can be manifested by neuropsychological stress (NPN), cognitive impairment and dementia, which negatively affect both metabolic processes and feelings of well-being and quality of life. The gradual development of neurovascular disorders, as well as chronic systemic inflammation associated with atherosclerosis and immune disorders are the causes of neuropsychological and neurophysiological disarrays. Cholinergic mechanisms and hyperactivation of the sympathetic-adrenal and hypothalamic-pituitary systems contribute to the secretion of stress hormones, increase mental stress against the background of chronic metabolic stress. Therefore, the assessment of the degree of NPN can be useful for characterizing the state of neuropsychological, neurophysiological processes and determining the treatment strategy for patients with type 2 DM. In general, current studies of neuropsychological parameters in patients with DM have shown that the disease adversely affects the neurocognitive characteristics of these patients. This is due to the main pathogenetic mechanisms (indicators of insulin resistance, markers of inflammation, atherogenesis and vascular dysfunction, changes in the secretion of stress hormones and neurotransmitters). Both type 2 DM and aging, can affect the development of neuropsychiatric abnormalities in patients with mental stress, memory, ability to concentrate, and cognition. Investigation of these effects and the development of methods for monitoring, prevention and pharmacotherapy of these disorders can be useful for improving the health of the elderly people, especially of patients with type 2 DM. Modern antidiabetic drugs can have a protective effect on the peripheral and central nervous system due to their hypoglycemic effects. Mechanisms of neuroprotective effect include antioxidant and anti-inflammatory action, antiapoptotic effect, enhanced neuronal differentiation. Agents for correction of intestinal microbiota also provide positive effects.

Glymphatic system dysfunction in patients with cluster headache

IntroductionThe aim of this study was to investigate alterations of the glymphatic system function in patients with cluster headache.MethodsWe enrolled patients with cluster headache and healthy controls, and they underwent brain magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI). We used the MRIcron and DSI studio programs for DTI preprocessing and DTI analysis with perivascular space (DTI‐ALPS) index calculation.ResultsFourteen patients with cluster headache and 23 healthy controls were enrolled. The DTI‐ALPS indexes of the groups were significantly different. The DTI‐ALPS index for the patients with cluster headache was lower than that for the healthy controls (1.586 vs. 1.786, p = 0.044). There was a significant negative correlation between the DTI‐ALPS index and age in the patients with cluster headache (r = −0.549, p = 0.042). However, the DTI‐ALPS index was not associated with other clinical characteristics, including disease duration and headache intensity (r = −0.405, p = 0.150; r = −0.048, p = 0.869, respectively).ConclusionPatients with cluster headache had a lower DTI‐ALPS index than the healthy controls; this might indicate glymphatic system dysfunction in the patients with cluster headache. Further research is required to determine whether glymphatic system dysfunction is related to the pathophysiology of cluster headache.

Normal glymphatic system function in patients with migraine: A pilot study.

No studies have evaluated the glymphatic system function in patients with migraine. In this pilot study, we evaluated and compared the alterations in the glymphatic system function in patients with migraine with healthy controls using a diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS) method. We also investigated the differences in the glymphatic system function table between patients with migraine with and without aura using the ALPS method. This field study used a cross-sectional study design. We prospectively enrolled patients with migraine and healthy controls. All brain magnetic resonance imaging (MRI), including DTI, in participants, patients with migraine, and healthy controls were obtained using the same MRI scanner. We calculated and compared the ALPS index between patients with migraine and healthy controls, and between patients with migraine with and without aura. In addition, we investigated the association between the glymphatic system function and the clinical characteristics of migraine. We enrolled 92 patients with migraine and 80healthy controls. There were no significant differences in the ALPS index between patients with migraine and healthy controls (1.655±0.335 [patients with migraine] vs. 1.713±0.297 [controls], difference = 0.058, 95% confidence interval [CI] of difference = -0.037 to 0.154, p=0.233), and between patients with migraine with and without aura (1.690±0.380 [with aura] vs. 1.645±0.323 [without aura], difference = -0.044, 95% CI of difference = -0.213 to 0.124, p=0.601). There was no significant correlation between the ALPS index and clinical characteristics of migraine, including age (r = -0.07, p=0.507), age at onset (r=0.07, p=0.552), disease duration (r = -0.12, p=0.306), attack frequency (r = -0.05, p=0.668), and headache intensity (r=0.00, p=0.976). There was no glymphatic system dysfunction in patients with migraine. Moreover, there were no differences in the glymphatic system function between patients with migraine with and without aura. We also demonstrated the feasibility of the ALPS method, which can be used for research on various neurological diseases. Further studies are needed to confirm our findings.

Neuroimaging evidence of glymphatic system dysfunction in possible REM sleep behavior disorder and Parkinson\u2019s disease

Alpha-synucleinopathy is postulated to be central to both idiopathic rapid eye movement sleep behaviour disorder (iRBD) and Parkinson’s disease (PD). Growing evidence suggests an association between the diminished clearance of α-synuclein and glymphatic system dysfunction. However, evidence accumulating primarily based on clinical data to support glymphatic system dysfunction in patients with iRBD and PD is currently insufficient. This study aimed to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship to clinical scores of disease severity in patients with possible iRBD (piRBDs) and those with PD. Further, we validated the correlation between the ALPS index and the prognosis of PD longitudinally. Overall, 168 patients with PD, 119 piRBDs, and 129 healthy controls were enroled. Among them, 50 patients with PD had been longitudinally reexamined. Patients with PD exhibited a lower ALPS index than those with piRBDs (P = 0.036), and both patient groups showed a lower ALPS index than healthy controls (P < 0.001 and P = 0.001). The ALPS index and elevated disease severity were negatively correlated in the piRBD and PD subgroups. Moreover, the ALPS index was correlated with cognitive decline in patients with PD in the longitudinal analyses. In conclusion, DTI-ALPS provided neuroimaging evidence of glymphatic system dysfunction in piRBDs and patients with PD; however, the potential of assessing the pathological progress of α-synucleinopathies as an indicator is worth verifying. Further development of imaging methods for glymphatic system function is also warranted.

Clinical manifestations and evaluation of cardiac autonomic neuropathy in diabetes mellitus and metabolic syndrome

A serious complication of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) is a dysfunction of the autonomic nervous system, which requires early evaluation for the effective treatment. The possibilities of pulse oximetry, which allows to assess heart rate variability in screening of autonomic nervous system dysfunction in patients with T2DM and MetS, have not yet been studied sufficiently.Objective: to evaluate the pulse oximetry effectiveness by comparing its results with the data of quantitative autonomic testing (QAT) to detect cardiac autonomic neuropathy (CAN) and clarify its degree in patients with T2DM and MetS.Patients and methods. The study included 30 patients with T2DM (mean age 63±7.9 years), 30 patients with MetS (mean age 61.5±9.1 years), 30 subjects from the control group (mean age 49.7±9.3 years). Patients underwent pulse oximetry, basic cardiovascular reflex tests, assessment of subjective sensations according to the NSC questionnaire, the severity of neurological deficit in the legs according to the NIS-LL scale and neuropathic pain syndrome according to the NTSS-9 scale.Results and discussion. In the group of patients with T2DM, severe CAN was detected in 13.3% of patients, moderate – in 40%. In the group of patients with MetS, severe CAN was detected in 10% of patients, moderate – also in 10%. In the control group, signs of moderate CAN were detected only in 3.3% of patients. The results of pulse oximetry tests with deep breathing were comparable to the QAT results (p&lt;0.001). Conclusion. Pulse oximetry can be used to diagnose CAN.

HP07: A 24-hour heart rate variability analysis in Tunisian patients under hemodialysis is an indicator of autonomic nervous system activity

Heart rate variability (HRV) is a useful tool to evaluate autonomic nervous system activity in patients under hemodialysis (HD). The aim of the study was to evaluate the autonomic nervous system activity in Tunisian patients under HD using HRV analysis. Patients and methods: It was a prospective study including 27 patients under HD for at least 3 months. A Holter-ECG recording was realized for 48 hours. Time- and frequency-domain were analyzed. Statistical analysis were done using SPSS20. Results: The different HRV parameters were decreased. Only LF/HF ratio was increased indicating a deviation of the sympatico-vagal balance. The time-domain analysis showed a significant variation of the RR and the RMSSD during sleep-wake cycle. The latter parameters were increased during sleep. The frequency-domain analysis showed a significant increase in HF and LF during sleep. Nevertheless, LF/HF ratio decreased during sleep while the LF increased, however, without being significantly different. Conclusion: Our study showed an autonomic nervous system dysfunction in patients under HD. This dysfunction was characterized by a hyperactivation of the sympathetic system associated to a decreased parasympathetic activity. However, the physiological activation of the parasympathetic system during sleep was preserved. A HRV alteration is an independent cardiovascular risk factor.

Correction of vegetative disorders in children with irritable bowel syndrome

Introduction. The article considers the formation of irritable bowel syndrome (IBS) in children. In recent years this pathology occurs more often among the adult and children population in many countries in the world. According to the modern view of the problem, this disease is considered a biopsychological disease, in the development of which an important role is played by the connection of psychological factors, dysfunctions of the autonomic nervous system, motor and secretory disorders of various parts of the intestine, which can cause the discomfort, changes of intestinal habits. All these factors lead to a decrease in the quality of life in children. Purpose of research. The main goal of this research is to study the peculiarities of the status of the autonomic nervous system in children with irritable bowel syndrome and to evaluate the effectiveness of the proposed therapy. Materials and methods One of the main methods for assessing the condition of the autonomic system in patients is cardiointervalography. During this examination, we calculated the index of tension, which is one of the main indicators of assessing the condition of this part of the nervous system. According to this index’s indicators, the vegetative system’s state can be divided into three main variants of functioning – vagotony, eutony, and sympathicotony. All patients were divided into groups according to the main complaints and course of IBS – IBS with constipation (IBS -C), IBS with diarrhea (IBS- D), a mixed form of IBS and an unclassified form of IBS. And also another two large groups were formed – main and control. Results. We analyzed the cardiointervalogram indicators in both groups of patients with different clinical variants of IBS. In the main group, we registered a statistically significant decrease in the index of tension and an improvement in autonomic nervous system dysfunction in patients with IBS with constipation and diarrhea. Indicators in these groups were changed from the state of vagotony and sympathicotonia to eutony. This indicates the restoration of the function of the normal function of the autonomic nervous system. Patients from the control group also showed changes in the index of tension, but the indicators stayed in the borders of vagotony and sympathicotony, and didn’t reach the level of eutony. Conclusions. Аfter the evaluation of the received data, it was proved that the use of hopanthenic acid in the complex therapy of irritable bowel syndrome effectively improve the status of the autonomic nervous system in children.

Specificities of Diagnosis and Treatment of Dental System Dysfunction in Patients with Malocclusion

Specificities of Diagnosis and Treatment of Dental System Dysfunction in Patients with Malocclusion

Glymphatic system dysfunction in obstructive sleep apnea evidenced by DTI-ALPS

ObjectivesThis study aimed to evaluate the glymphatic system function in patients with obstructive sleep apnea (OSA) compared to healthy controls using diffusion tensor imaging (DTI) with the perivascular space (DTI-ALPS) method. Our hypothesis is that patients with OSA may have glymphatic system dysfunction, which is correlated with OSA severity. MethodsWe enrolled 24 patients with OSA and 24 healthy controls. All participants underwent DTI magnetic resonance imaging (MRI) using the same 3T MRI scanner, and we calculated the DTI-ALPS index from the DTI. We evaluated the differences in the DTI-ALPS index between patients with OSA and healthy controls. In addition, we conducted a correlation analysis between the DTI-ALPS index and clinical characteristics. ResultsThe DTI-ALPS index was significantly different between the groups. The DTI-ALPS in patients with OSA was significantly lower than in healthy controls (1.30450 vs. 1.61600, p = 0.0006). Furthermore, the DTI-ALPS index was significantly negatively correlated with the apnea–hypopnea index in sleep stage N (r = −0.427, p = 0.042) and oxygen desaturation index during sleep N (r = −0.497, p = 0.036). ConclusionWe successfully demonstrated glymphatic system dysfunction in patients with OSA. In addition, glymphatic system dysfunction is well correlated with OSA severity, especially during sleep stage N. Thus, these findings can explain the effects of OSA on increased risk of developing dementia and highlight the importance of OSA treatment.

Evaluation and treatment of peripheral nervous system dysfunction in patients with prediabetes

The worldwide prevalence of prediabetes is steadily increasing, with up to a third of patients already showing signs of diabetic neuropathy (DN). Prediabetes includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or a combination of both.Recent diagnostic criteria of prediabetes according to Russian, European, and American clinical guidelines are presented. The review covers the most common forms of DN in patients with prediabetes (distal symmetric sensory polyneuropathy, painful DN, cardiovascular autonomic neuropathy) and their prevalence. Recommended methods of DN screening are discussed: diagnostic scales, sensory testing, nerve conduction study, autonomic testing, corneal confocal microscopy. The results of studies evaluating instrumental methods for diagnosing peripheral nervous system (PNS) dysfunction in prediabetes are discussed. Management tactics in patients with prediabetes and PNS dysfunction should include non-pharmacological and pharmacological interventions. Combining a low-calorie diet and regular physical activity can delay the development of diabetes mellitus and reduce the severity of neuropathic pain. In patients with painful DN, the first-line therapy includes pregabalin, gabapentin, and duloxetine. Since there is no current data on the effect of hypoglycemic therapy on the risks of development and/or progression of DN in patients with prediabetes, antioxidants are considered pathogenetic therapy. Alpha-lipoic acid (Berlition®) in the management of patients with prediabetes is discussed.

Glymphatic system dysfunction in patients with juvenile myoclonic epilepsy

The glymphatic system is a glial cell-dependent waste clearance pathway in the brain that is essential for the maintenance of brain homeostasis. In this study, we evaluated glymphatic system function in patients with juvenile myoclonic epilepsy (JME) compared with healthy controls. Patients with JME and healthy controls were retrospectively enrolled in this study. All the participants underwent brain diffusion tensor imaging (DTI). The "DTI-analysis along the perivascular space (ALPS)"-index was calculated to evaluate the glymphatic system function of the participants. The ALPS-indices of the patients with JME were compared with those of the healthy controls. In addition, the correlations between ALPS-index and the clinical characteristics of the patients with JME were analyzed to validate changes in glymphatic system function. A total of 39 patients with JME and 38 healthy controls were enrolled in this study. The mean ALPS- index of the patients with JME was significantly lower than that of the healthy controls (1.541 vs. 1.653, p = 0.041). ALPS-index was negatively correlated with age in patients with JME (r = -0.375, p = 0.018). However, ALPS-index was not correlated with age at onset, duration of epilepsy, or anti-seizure medication load in patients with JME. This study is the first in which the ALPS method was used to demonstrate that patients with JME have significant glymphatic system dysfunction. The results also show that glymphatic system index is negatively correlated with age in patients with JME, a finding which demonstrates that the glymphatic system function of patients with JME gradually declines with age. The ALPS-index might be a potential biomarker for monitoring glymphatic system function in patients with epilepsy.

Oxytocin system dysfunction in patients with treatment-resistant schizophrenia: Alterations of blood oxytocin levels and effect of a genetic variant of OXTR

Treatment-resistant schizophrenia (TRS) has a quite complex pathophysiology that includes not only severe positive symptoms but also other symptom domains. Much attention has been devoted to the overlapping psychological and biological profiles of schizophrenia and autistic spectrum disorder (ASD). We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on general cognitive and social cognitive impairment and oxytocin system dysfunction. Our analyses revealed that there was no difference in oxytocin concentration among the three groups. The TRS patients’ oxytocin blood concentrations were positively correlated with their processing speed and theory-of-mind scores, whereas the RemSZ and ASD groups had no significant relation with any measures. Rs53576, a single nucleotide polymorphism on the oxytocin receptor gene, affected social cognition abilities in the schizophrenia group. Although the overall findings are preliminary, they indicate that oxytocin system dysfunction could be involved in the serious cognitive deficits in TRS patients. Further, these results suggest that patients with TRS might have early neurodevelopmental abnormalities based on their shared biological features with ASD patients.