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Saudi Pharmaceutical Journal : SPJ :... Oct 2023Parkinson's disease (PD) is one of the major neurodegenerative disorders and the prevalence is expected to increase during the next couple of decades. There is a need...
BACKGROUND
Parkinson's disease (PD) is one of the major neurodegenerative disorders and the prevalence is expected to increase during the next couple of decades. There is a need for safe and effective therapeutic regimen that can effectively manage this neurotoxicity. The leaves and several other parts of are known to possess number of medicinal properties. The purpose of this study was to examine the neuroprotective role of in an experimental model of haloperidol-induced P.D.
MATERIALS AND METHODS
Five groups of rats were randomly assigned into different groups. Intraperitoneal haloperidol 1 mg/kg was given to the inducer group and 0.5% CMC to the normal control. The reference standard was syndopa 10 mg/kg, p.o., and the test group animals received ethanolic extract at 200 and 400 mg/kg orally for one week. Rats exposed to haloperidol were assessed for behavioral, neurochemical, and histopathological parameters.
RESULTS
leaves extract dose-dependently increased behavioral activity and muscle coordination. The extract at 400 mg/kg was found to increase significantly ( < 0.001) the central square activity in open-field test, compared to haloperidol treated rats. In stepping test, both tested doses of (200 mg and 400 mg/kg) were found to significantly ( < 0.001) reduce akinesia, besides these doses also decreased the catatonic responses induced by haloperidol. Further, the extraction treatment (200 mg and 400 mg/kg) significantly ( < 0.001) decreased malonaldehyde and increased antioxidant enzymes like catalase compared to the control group. Histopathological changes in the test group showed a significant reduction in haloperidol damage to normal morphology in cortical, hippocampus, substantia nigra, and pyramidal.
CONCLUSION
The observations of the study suggest that attenuated the haloperidol-induced neurological changes, indicating that the plant might benefit in the treatment of Parkinson's disease. The activity of could be linked to its antioxidant property. Since, the drug is traditionally used in different parts of world; it could be a promising agent if more research establishes its safety and efficacy in other experimental models of Parkinson's Disease.
PubMed: 37771955
DOI: 10.1016/j.jsps.2023.101791 -
Frontiers in Neuroinformatics 2023Coordinated Reset Deep Brain Stimulation (CR DBS) is a novel DBS approach for treating Parkinson's disease (PD) that uses lower levels of burst stimulation through...
INTRODUCTION
Coordinated Reset Deep Brain Stimulation (CR DBS) is a novel DBS approach for treating Parkinson's disease (PD) that uses lower levels of burst stimulation through multiple contacts of the DBS lead. Though CR DBS has been demonstrated to have sustained therapeutic effects on rigidity, tremor, bradykinesia, and akinesia following cessation of stimulation, i.e., carryover effect, its effect on Parkinsonian gait has not been well studied. Impaired gait is a disabling symptom of PD, often associated with a higher risk of falling and a reduced quality of life. The goal of this study was to explore the carryover effect of subthalamic CR DBS on Parkinsonian gait.
METHODS
Three non-human primates (NHPs) were rendered Parkinsonian and implanted with a DBS lead in the subthalamic nucleus (STN). For each animal, STN CR DBS was delivered for several hours per day across five consecutive days. A clinical rating scale modified for NHP use (mUPDRS) was administered every morning to monitor the carryover effect of CR DBS on rigidity, tremor, akinesia, and bradykinesia. Gait was assessed quantitatively before and after STN CR DBS. The stride length and swing speed were calculated and compared to the baseline, pre-stimulation condition.
RESULTS
In all three animals, carryover improvements in rigidity, bradykinesia, and akinesia were observed after CR DBS. Increased swing speed was observed in all the animals; however, improvement in stride length was only observed in NHP B2. In addition, STN CR DBS using two different burst frequencies was evaluated in NHP B2, and differential effects on the mUPDRS score and gait were observed.
DISCUSSION
Although preliminary, our results indicate that STN CR DBS can improve Parkinsonian gait together with other motor signs when stimulation parameters are properly selected. This study further supports the continued development of CR DBS as a novel therapy for PD and highlights the importance of parameter selection in its clinical application.
PubMed: 37692361
DOI: 10.3389/fninf.2023.1185723 -
Neurotherapeutics : the Journal of the... Oct 2023Traumatic brain injury (TBI), a neurovascular injury caused by external force, is a common diagnosis among veterans and those experiencing homelessness (HL). There is a... (Review)
Review
Traumatic brain injury (TBI), a neurovascular injury caused by external force, is a common diagnosis among veterans and those experiencing homelessness (HL). There is a significant overlap in the veteran and homeless population, possibly accounting for the two to seven times greater incidence of TBI among those experiencing HL than the general population. Despite these statistics, individuals experiencing HL are often underdiagnosed and ineffectively treated for TBI. We introduced a novel model of HL. Over 5 weeks, adult Sprague-Dawley rats were randomly assigned to one of the following conditions: TBI only, HL only, TBI + HL, or control (n = 9 per group). To emulate HL, animals (2 animals per cage) were exposed to soiled beddings for 5 weeks. Subsequently, animals were introduced to TBI by using the moderate controlled cortical impact model, then underwent 4 consecutive days of behavioral testing (beam walk (BW), elevated body swing test (EBST), forelimb akinesia (FA), paw grasp (PG), Rotorod, and elevated T-maze). Nissl staining was performed to determine the peri-impact cell survival and the integrity of corpus callosum area. Motor function was significantly impaired by TBI, regardless of housing (beam walk or BW 85.0%, forelimb akinesia or FA 104.7%, and paw grasp or PG 100% greater deficit compared to control). Deficits were worsened by HL in TBI rats (BW 93.3%, FA 40.5%, and PG 50% greater deficit). Two-way ANOVA revealed BW (F(4, 160) = 31.69, p < 0.0001), FA (F(4, 160) = 13.71, p < 0.0001), PG (F(4, 160) = 3.873, p = 0.005), Rotorod (F(4, 160), p = 1.116), and EBST (F(4, 160) = 6.929, p < 0.0001) showed significant differences between groups. The Rotorod and EBST tests showed TBI-induced functional deficits when analyzed by day, but these deficits were not exacerbated by HL. TBI only and TBI + HL rats exhibited typical cortical impact damage (F(3,95) = 51.75, p < 0.0001) and peri-impact cell loss compared to control group (F(3,238) = 47.34, p < 0.0001). Most notably, TBI + HL rats showed significant alterations in WM area measured via the corpus callosum (F(3, 95) = 3.764, p = 0.0133). Worsened behavioral outcomes displayed by TBI + HL rats compared to TBI alone suggest HL contributes to TBI functional deficits. While an intact white matter, such as the corpus callosum, may lessen the consequent functional deficits associated with TBI by enhancing hemispheric communications, there are likely alternative cellular and molecular pathways mitigating TBI-associated inflammatory or oxidative stress responses. Here, we showed that the environmental condition of the patient, i.e., HL, participates in white matter integrity and behavioral outcomes, suggesting its key role in the disease diagnosis to aptly treat TBI patients.
Topics: Humans; Adult; Rats; Animals; Rats, Sprague-Dawley; Brain Injuries, Traumatic; White Matter; Ill-Housed Persons; Comorbidity
PubMed: 37639189
DOI: 10.1007/s13311-023-01419-8 -
Neurology and Therapy Dec 2023Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day...
INTRODUCTION
Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD.
METHODS
Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of "Off" time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700-4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized "Off" and "On" time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Sleep Scale-2 (PDSS-2), 39-item Parkinson's Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L).
RESULTS
Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, "On" time without troublesome dyskinesia and "Off" time were improved from baseline (mean [standard deviation (SD)] change in normalized "On" time without troublesome dyskinesia, 3.8 [3.3] hours; normalized "Off" time, -3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved.
CONCLUSION
Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov identifier NCT03781167.
PubMed: 37632656
DOI: 10.1007/s40120-023-00533-1 -
Life (Basel, Switzerland) Aug 2023Takotsubo cardiomyopathy (TCM) is a reversible form of cardiomyopathy characterized by transient regional systolic dysfunction of the left ventricle.
INTRODUCTION
Takotsubo cardiomyopathy (TCM) is a reversible form of cardiomyopathy characterized by transient regional systolic dysfunction of the left ventricle.
CASE OUTLINE
A 78-year-old woman was admitted to the general hospital due to acute inferior STEMI late presentation. Two days after admission, the patient reported intense chest pain and an ECG registered diffuse ST-segment elevation in all leads with ST-segment denivelation in aVR. The patient also showed clinical signs of cardiogenic shock and was referred to a reference institution for further evaluation. Echocardiography revealed akinesia of all medioapical segments, dynamic obstruction of the left ventricular outflow tract (LVOT), moderate mitral regurgitation, and pericardial effusion. Coronary angiography showed the suboccluded right coronary artery, and a primary percutaneous coronary intervention was performed, which involved implanting a drug-eluting stent. The patient's condition worsened as pericardial effusion increased and led to tamponade. Pericardiocentesis was performed, resulting in the patient's stabilization. At this point, significant gradients at the LVOT and pericardial effusion were not registered. After eight days without symptoms and stable status, the patient was discharged.
CONCLUSIONS
The simultaneous presence of AMI and TCM increases the risk of developing cardiogenic shock. The cardio-circulatory profile of these patients is different from those with AMI.
PubMed: 37629626
DOI: 10.3390/life13081770 -
Biomedicines Jul 2023Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor alterations. Typical motor symptoms include resting tremors, bradykinesia...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor alterations. Typical motor symptoms include resting tremors, bradykinesia (hypokinesia or akinesia), muscular stiffness, gait alterations, and postural instability. In this context, neurorehabilitation may have a pivotal role in slowing the progression of PD, using both conventional and innovative rehabilitation approaches. Thirty patients (15 males and 15 females) affected by PD were enrolled in our study. We randomly divided the patients into two groups, an experimental group (EG) and a control group (CG). In particular, the EG performed gait and balance training using the Rysen system, which is an innovative body weight support (BWS) system, whilst the CG received conventional physiotherapy. Both groups underwent 20 sessions, five times weekly, with each session lasting about 40 min. At the end of the training sessions (T1), we found that both groups (EG and CG) achieved clinical improvements, although the EG showed better scores for post-treatment regarding global motor functioning and postural stability compared to the CG. In conclusion, our results suggest that the Rysen system, which is an innovative BWS tool, could be considered a valid device for improving postural control and global motor functions, when compared to conventional gait training, in patients affected by PD.
PubMed: 37626645
DOI: 10.3390/biomedicines11082148 -
Radiology Case Reports Oct 2023Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder of obscure etiology characterized by significant infiltration of IgG4-positive...
Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder of obscure etiology characterized by significant infiltration of IgG4-positive plasma cells toward several organs. Coronary artery involvement is rarely seen in IgG4-RD patients; thereby, we aim to outline the noninvasive imaging findings of this rare case. Cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) from a 15-year-old female diagnosed with IgG4-RD via histopathological assessment of orbital biopsy, were analyzed. CMR showed a severely reduced left ventricular ejection fraction and akinesia of the basal to mid-lateral, anterior, and septal walls. Inflammation of the basal to apical lateral wall and subendocardial infarction of the basal to apical lateral and mid inferoseptal walls were also evident. CCTA findings showed stenosis in branches of the left main artery (LM), left anterior descending artery (LAD), and right coronary artery (RCA), aortitis, and aortic wall thickening. After courses of proper treatment with prednisolone, Cellcept, and adalimumab, follow-up CMR showed significant improvement in LV systolic function and resolution of inflammation. Although IgG4-RD is an uncommon cause of coronary artery disease, it can cause lethal complications such as myocardial infarction. Hence, clinicians should be aware of cardiac complications in these patients.
PubMed: 37609068
DOI: 10.1016/j.radcr.2023.07.062 -
Journal of Neurosurgery. Case Lessons Aug 2023The supplementary motor area (SMA) is essential in facilitating the commencement and coordination of complex self-initiated movements. Its complex functional...
BACKGROUND
The supplementary motor area (SMA) is essential in facilitating the commencement and coordination of complex self-initiated movements. Its complex functional connectivity poses a great risk for postoperative neurological deterioration. SMA syndrome can occur after tumor resection and comprises hemiakinesia and akinetic mutism (often, but unpredictably temporary). Although awake surgery is preferred for mapping and monitoring eloquent areas, connectomics is emerging as a novel technique to tailor neurosurgical approaches and predict functional prognosis, as illustrated in this case.
OBSERVATIONS
The authors report on a patient presenting with recurrent oligodendroglioma after subtotal resection 7 years earlier. After extensive neuropsychological and neuroradiological assessment (including connectomics), awake surgery was indicated. No intraoperative deficits were recorded; however, the patient presented with postoperative right-sided akinesia and mutism. Postoperative neuroimaging demonstrated the connectome overlapping the preoperative one, and indeed, neurological symptoms resolved after 3 days.
LESSONS
Comparison of the pre- and postoperative connectome can be used to objectively evaluate surgical outcomes and assess patient prognosis. To the best of the authors' knowledge, this is the first case demonstrating the feasibility of quantitative functional connectivity analysis as a prognostic tool for neurological improvement after surgery. A better understanding of brain networks is instrumental for improving diagnosis, prognosis, and treatment of neuro-oncological patients.
PubMed: 37581598
DOI: 10.3171/CASE23286