Pharmacokinetics of Levodopa and 3-O-Methyldopa in Parkinsonian Patients Treated with Levodopa and Ropinirole and in Patients with Motor Complications

Parkinson’s disease (PD) is a progressive, neurodegenerative disorder primarily affecting dopaminergic neuronal systems, with impaired motor function as a consequence. The most effective treatment for PD remains the administration of oral levodopa (LD). Long-term LD treatment is frequently associated with motor fluctuations and dyskinesias, which exert a serious impact on a patient’s quality of life. The aim of our study was to determine the pharmacokinetics of LD: used as monotherapy or in combination with ropinirole, in patients with advanced PD. Furthermore, an effect of ropinirole on the pharmacokinetics of 3-OMD (a major LD metabolite) was assessed. We also investigated the correlation between the pharmacokinetic parameters of LD and 3-OMD and the occurrence of motor complications. Twenty-seven patients with idiopathic PD participated in the study. Thirteen patients received both LD and ropinirole, and fourteen administered LD monotherapy. Among 27 patients, twelve experienced fluctuations and/or dyskinesias, whereas fifteen were free of motor complications. Inter- and intra-individual variation in the LD and 3-OMD concentrations were observed. There were no significant differences in the LD and 3-OMD concentrations between the patients treated with a combined therapy of LD and ropinirole, and LD monotherapy. There were no significant differences in the LD concentrations in patients with and without motor complications; however, plasma 3-OMD levels were significantly higher in patients with motor complications. A linear one-compartment pharmacokinetic model with the first-order absorption was adopted for LD and 3-OMD. Only mean exit (residence) time for 3-OMD was significantly shorter in patients treated with ropinirole. Lag time, V/F, CL/F and tmax of LD had significantly lower values in patients with motor complications. On the other hand, AUC were significantly higher in these patients, both for LD and 3-OMD. 3-OMD Cmax was significantly higher in patients with motor complications as well. Our results showed that ropinirole does not influence LD or 3-OMD concentrations. Higher 3-OMD levels play a role in inducing motor complications during long-term levodopa therapy.

Perspectives and value of external control devices (exoskeletons) for effective rehabilitation of patients with impaired motor function

The purpose of this work is to study the prospects for the development and use of exoskeletons (robotic external control devices) for the rehabilitation of patients with impaired motor function. The authors consider the modern topical task - creating a complex device for the most effective rehabilitation of patients with impaired motor function. S such cases include patients who suffered from a stroke and spinal injury or have lost the ability to move independently and continue their professional and social activities. The literature search was carried out in the Scopus, Web of Science, MedLine, Pubmed, The Cochrane Library, EMBASE, RSCI, Elibrary databases, with main inclusion criteria: (a) motor or neuromotor rehabilitation, (b) exoskeletons, (c) mobile robotic devices. The significant gain in the report number on this topic has been registered in the last five years. The primary trend in research is both the development of wearable robotic exoskeletons and the combination of data collected from several sensors. This can promote the development of intelligent algorithms. However, no papers have yet been published showing the results of using such self-learning systems. The analysis of the successful development of exoskeletons available globally has received admissions on their countries’ markets and have shown the best results reliably in conducting rehabilitation courses. The controversial results of 34 systematic reviews and meta-analyzes are discussed. Published results should be viewed with caution, as most studies have protocol errors and preliminary multicenter studies. Possible new forms of individual and collective use of robotic devices are discussed. The most important for developing this direction are identified issues related to the development of brain-computer neuro interfaces. Prospective ways for further research in optimal rehabilitation of patients with impaired motor function and their resocialization are outlined.

Functional recovery in post-stroke patients on hemodialysis during the convalescent phase: a comparison with those not undergoing hemodialysis

Background Low physical fitness is often found in patients undergoing hemodialysis. It may be possible that the recovery of impaired motor function with rehabilitative training might be affected when the patient is on hemodialysis. So far, however, no researcher has clinically investigated this issue in post-stroke patients. The purpose of this study is to clarify the difference of functional recovery during the convalescent phase between post-stroke patients with and without hemodialysis. Methods A cohort of 82 post-stroke hemiparetic patients who were admitted to our rehabilitation hospital, were subjected. On the day of admission and discharge, some clinical parameters including Functional Independence Measure (FIM) and Functional Ambulation Category (FAC) were evaluated for each patient. The changes during the hospitalization and the values at the discharge in these parameters were statistically compared between the patients with and without hemodialysis. Results The FIM motor score at the discharge was significantly lower in hemodialysis patients than non-hemodialysis patients (64.7 ± 21.2 points in hemodialysis patients and 81.8 ± 28.0 points in non-hemodialysis patients, p < 0.05). In addition, the frequency of FAC at the discharge of ≥ 3 was significantly lower in hemodialysis patients than non-hemodialysis patients (40.0% in hemodialysis patients and 72.2% in non-hemodialysis patients, p < 0.05). Conclusion In patients undergoing hemodialysis seem to experience a worse functional recovery during the convalescent phase compared to those not undergoing hemodialysis. We might have to modify the rehabilitative program during the convalescent phase after stroke if the patient was on hemodialysis.

EEG hyperscanning in motor rehabilitation: a position paper

Studying the human brain during interpersonal interaction allows us to answer many questions related to motor control and cognition. For instance, what happens in the brain when two people walking side by side begin to change their gait and match cadences? Adapted from the neuroimaging techniques used in single-brain measurements, hyperscanning (HS) is a technique used to measure brain activity from two or more individuals simultaneously. Thus far, HS has primarily focused on healthy participants during social interactions in order to characterize inter-brain dynamics. Here, we advocate for expanding the use of this electroencephalography hyperscanning (EEG-HS) technique to rehabilitation paradigms in individuals with neurological diagnoses, namely stroke, spinal cord injury (SCI), Parkinson’s disease (PD), and traumatic brain injury (TBI). We claim that EEG-HS in patient populations with impaired motor function is particularly relevant and could provide additional insight on neural dynamics, optimizing rehabilitation strategies for each individual patient. In addition, we discuss future technologies related to EEG-HS that could be developed for use in the clinic as well as technical limitations to be considered in these proposed settings.

A Novel 3-RRR Spherical Parallel Instrument for Daily Living Emulation (SPINDLE) for Functional Rehabilitation of Patients with Stroke

Various robotic rehabilitation devices have been developed for acute stroke patients to ease therapist’s efforts and provide high-intensity training, which resulted in improved strength and functional recovery of patients; however, these improvements did not always transfer to the performance of activities of daily living (ADLs). This is because previous robotic training focuses on the proximal joints or training with exoskeleton-type devices, which do not reflect how humans interact with the environment. To improve the training effect of ADLs, a new robotic training paradigm is suggested with a parallel manipulator that mimics rotational ADL tasks. This study presents training of the proximal and distal joints simultaneously while performing manipulation tasks in a device named spherical parallel instrument for daily living emulation (SPINDLE). Six representative ADLs were chosen to show that both proximal and distal joints are trained when performing tasks with SPINDLE, as compared to the natural ADLs. These results show that SPINDLE can train individuals with movements similar to the ADLs while interacting with the manipulator. We envision using this compact tabletop device as a home-training device to increase the performance of ADLs by restoring the impaired motor function of stroke patients, leading to improved quality of life.

Gut Digestive Function and Microbiome after Correction of Experimental Dysbiosis in Rats by Indigenous Bifidobacteria

In recent years, great interest has arisen in the use of autoprobiotics (indigenous bacteria isolated from the organism and introduced into the same organism after growing). This study aimed to evaluate the effects of indigenous bifidobacteria on intestinal microbiota and digestive enzymes in a rat model of antibiotic-associated dysbiosis. Our results showed that indigenous bifidobacteria (the Bf group) accelerate the disappearance of dyspeptic symptoms in rats and prevent an increase in chyme mass in the upper intestine compared to the group without autoprobiotics (the C1 group), but significantly increase the mass of chyme in the colon compared to the C1 group and the control group (healthy animals). In the Bf group in the gut microbiota, the content of opportunistic bacteria (Proteus spp., enteropathogenic Escherichia coli) decreased, and the content of some beneficial bacteria (Bifidobacterium spp., Dorea spp., Blautia spp., the genus Ruminococcus, Prevotella, Oscillospira) changed compared to the control group. Unlike the C1 group, in the Bf group there was no decrease in the specific activities of maltase and alkaline phosphatase in the mucosa of the upper intestine, but the specific activity of maltase was decreased in the colon chyme compared to the control and C1 groups. In the Bf group, the specific activity of aminopeptidase N was reduced in the duodenum mucosa and the colon chyme compared to the control group. We concluded that indigenous bifidobacteria can protect the microbiota and intestinal digestive enzymes in the intestine from disorders caused by dysbiosis; however, there may be impaired motor function of the colon.

Abstract P203: Assessing Sexual Dysfunction Among Stroke Survivors and Barriers to Address This Issue by Healthcare Providers at a Latin American Reference Hospital

Background: Sexual dysfunction affects at least one half of patients after a stroke. Problems related to sexual function are rarely assessed or addressed by physicians. Objective: To determine the frequency and factors associated with sexual dysfunction among stroke survivors and self-reported barriers of physicians to discuss sexual dysfunction during regular consultation. Methods: We administered a questionnaire to a cross-sectional sample of stroke survivors to assess the frequency and factors associated with sexual dysfunction and the aspects of sexuality most commonly affected by stroke. A qualitative approach was used to determine the willingness to address sexual issues and related barriers among physicians participating in the study. Results: Among 150 patients, sexual dysfunction was identified in 89 (59%). Only 10% self-reported their sexual function as optimal. Markedly decreased frequency of sexual encounters (49%) and markedly decreased sexual desire (33%) were the aspects of sexual function most commonly reported by patients after a stroke. Fear of having a new stroke [OR:3.2, 95% CI (1.5 – 6.3)], depression [OR:2.1, 95% CI (1.0– 4.3)], and self-perception of having impaired motor function [OR:2.5, 95% CI (1.2 – 5.0)] were significantly associated with sexual dysfunction. In the qualitative assessment of physicians (N= 15), when asked how often they addressed sexual aspects during regular consultation with a stroke survivor, none answered “very often”, and only 8 (51%) answered “sometimes”. At the end of the study, 10 (66%) physicians verbalized the perception that addressing this issue encouraged their patents to be more open to personal concerns and prompted a stronger doctor-patient relationship. Conclusion: Sexual dysfunction affected more than a half of stroke survivors, and was significantly associated with depression, fear of having a new stroke, and with the self-perception of impaired motor function. Addressing sexual issues during the regular consult by physicians was infrequent. Barriers reported by physicians included limited time during regular consultation and the belief that this issue should be addressed under the scope of other specialties.

Dermatomyositis syndrome in small cell lung cancer

Dermatomyositis is a progressive systemic disease clinically manifested by a muscle lesion with impaired motor function as well as skin rashes, often in the form of erythema. In some cases, dermatomyositis can be the onset of cancer. In this regard, the doctor is required to be highly alert and focused on detecting the tumor process in patients with progressive muscle weakness and characteristic skin manifestations of dermatomyositis. The article presents a clinical case of paraneoplastic dermatomyositis co‐existing with small cell lung cancer. The malignancy was diagnosed during cancer screening in a patient with classic manifestations of dermatomyositis. Improvement of clinical manifestations of dermatomyositis appeared with glucocorticosteroid therapy and surgical treatment, but the patient died, since small cell lung cancer has an aggressive clinical course with an unfavorable prognosis.

THE PREVALENCE OF ANKYLOGLOSIA TAKING INTO ACCOUNT ANATOMO-PHYSIOLOGICAL FEATURES OF THE MAXILLOFACIAL REGION IN CHILDREN OF VOLGOGRAD

The article is devoted to the study of the prevalence of ankyloglossia in children from 5 to 13 years of age, taking into account the anatomical and physiological characteristics of the maxillofacial region. Functional tests are proposed for the study of language motility and their assessment is carried out on a 4-point system. The studies were carried out after obtaining the written consent of the parents, taking into account the recommendations of the Ethics Committee. It is established that the prevalence of ankyloglossia is (6,96 ± 0,053) % of the number of examined children in Volgograd. It was noted that almost all the examined had impaired motor function of the tongue, requiring surgical treatment.

Dopamine-loaded poly (butyl cyanoacrylate) nanoparticles reverse behavioral deficits in Parkinson’s animal models

Aim: Parkinson's disease (PD) is a neurological disorder resulting from decreased dopamine (DA) secretion in the brain, which reflects impaired motor function. Thus, a drug-delivery system for releasing DA into the brain would be of crucial importance. Materials & methods: We herein examined the in vivo drug efficiency of novel poly-butyl-cyanoacrylate nanoparticles loaded with DA (DA-PBCA NPs). Results & conclusion: The NPs were able to pass through the blood–brain barrier and improve brain structure and function in the PD animal models. Moreover, we found a reduced α-synucleinopathy in the animal model brains after the NPs administration. Thus, the NPs seem to be a reliable DA delivery system for treating PD patients.