Systemic Review on Parkinson’s Disease Medications, Emphasizing on Three Recently Approved Drugs to Control Parkinson’s Symptoms

Parkinson’s Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia. Other non-motor symptoms include pain, depression, anxiety, and psychosis. This disease affects up to ten million people worldwide. The pathophysiology behind PD is due to the neurodegeneration of the nigrostriatal pathway. There are many conventional drugs used in the treatment of PD. However, there are limitations associated with conventional drugs. For instance, levodopa is associated with the on-off phenomenon, and it may induce wearing off as time progresses. Therefore, this review aimed to analyze the newly approved drugs by the United States-Food and Drug Administration (US-FDA) from 2016–2019 as the adjuvant therapy for the treatment of PD symptoms in terms of efficacy and safety. The new drugs include safinamide, istradefylline and pimavanserin. From this review, safinamide is considered to be more efficacious and safer as the adjunct therapy to levodopa as compared to istradefylline in controlling the motor symptoms. In Study 016, both safinamide 50 mg (p = 0.0138) and 100 mg (p = 0.0006) have improved the Unified Parkinson’s Disease Rating Scale (UPDRS) part III score as compared to placebo. Improvement in Clinical Global Impression—Change (CGI-C), Clinical Global Impression—Severity of Illness (CGI-S) and off time were also seen in both groups of patients following the morning levodopa dose. Pimavanserin also showed favorable effects in ameliorating the symptoms of Parkinson’s Disease Psychosis (PDP). A combination of conventional therapy and non-pharmacological treatment is warranted to enhance the well-being of PD patients.

Neuroleptic Malignant Syndrome in an Elderly Patient with Bipolar Disorder

Neuroleptic malignant syndrome (NMS) is a well-known and potentially fatal complication of antipsychotic use. The elderly population, with multiple risk factors, are more vulnerable to this condition. We described a case of an 80-yearold man with bipolar disorder, previously on oral extended-release sodium valproate, aripiprazole and long-acting injectable paliperidone, who developed NMS. He presented with generalised muscle rigidity, fever, fluctuating blood pressure and elevated creatinine kinase during his hospitalisation for a manic episode. Contributing factors included old age, underlying vascular Parkinsonism, electrolyte imbalance, intercurrent lung infection with acute exacerbation of chronic obstructive pulmonary disease, hyperactive delirium, and repeated administration of parenteral typical antipsychotic. Antipsychotics were withheld promptly, and the patient was treated with dantrolene, bromocriptine and amantadine. His symptoms resolved after a week. He subsequently remained well with oral extended-release sodium valproate alone. Relevant clinical points are discussed. Clinical vigilance, close interdisciplinary cooperation, and prompt interventions are keys to successful to management of NMS in elderly patients.

Effects of Remifentanil and Sufentanil Anesthesia on Cardiac Function and Serological Parameters in Congenital Heart Surgery

In this study, we have investigated feasibility of remifentanil and sufentanil anesthesia in children with congenital heart disease surgery and its effects on cardiac function and serological parameters. For this purpose, a retrospective study was conducted on 120 children with congenital heart disease who underwent repair of ventricular septum or atrial septum in our hospital, specifically from January 2016 to January 2018, and 60 patients in each group were randomly divided into the control and treatment groups, respectively. The control group was anesthetized with sufentanil, and the treatment group was anesthetized with remifentanil. The heart function, serological indexes, and adverse reactions were observed and compared. We have observed that there was no significant difference in HR levels between these groups ( P > 0.05 ), but SDP and DBP values of the two groups were decreased after anesthetic induction ( P < 0.05 ). ACH, cortisol, and lactic acid in the treatment group were significantly lower than those in the control group, and the difference was statistically significant ( P < 0.05 ). The incidence of bradycardia, nausea and vomiting, hypotension, muscle rigidity, and respiratory depression in the treatment group was 16.67% lower than that in the control group ( P < 0.05 ). Remifentanil has less influence on hemodynamics and a better analgesic effect than fentanyl in inhibiting stress response in congenital heart surgery, which provides reference and basis for children congenital heart surgery.

Comparative Analysis of Acute Levodopa Challenge Test and the Outcomes of Deep Brain Stimulation in Parkinson's Disease

Background We study the correlation between the preoperative levodopa challenge test and the efficacy of deep brain stimulation (DBS) surgery in Parkinson's disease (PD). Methods Fifty patients with PD who underwent DBS treatment in our hospital from October 2016 to October 2017 were enrolled in this study. Using the Unified Parkinson Disease Rating Scale-III (UPDRS-III) as an indicator, we analyzed the improvement in motor symptoms on the levodopa challenge test and by DBS surgery. We also discussed the correlation between the effects of the levodopa challenge test and DBS surgery. Results There was no correlation between the results of the levodopa challenge test and DBS surgery. There was a linear correlation between muscle rigidity and bradykinesia, whereas the linear correlation between other symptoms was weak. Conclusion The levodopa challenge test can be used as a screening tool for patients undergoing DBS surgery, and can predict the degree of improvement in muscle rigidity and bradykinesia surgery. However, the prediction of the degree of improvement of total motor symptoms is poor.

Detection of Parkinsonian Motor Symptoms Using Non-Invasive Motion Sensing Technology

Parkinson’s Disease (PD) is characterized by impaired movement, resting tremor, and muscle rigidity. The Unified PD Rating Scale (UPDRS) is a standardized protocol used by neurologists to measure progression of disease as well as evaluation of treatments. However, this examination is subjective, time consuming, and results can be affected by stress, diet, or sleep. Our goal is to develop a non-invasive device that can record objective clinically-relevant measurements during subtasks of the UPDRS to allow for remote evaluations, which would be beneficial considering the frequency of clinical visits for medication adjustments. Five healthy individuals (ages 21-59) completed UPDRS tasks 3.6 (pronation/supination of hands) and 3.17 (rest tremor amplitude). Participants performed these tasks twice, first normally and second simulating PD patients (tremor, bradykinesia, reduction of movement amplitude) after viewing example videos. Motion data including linear and angular accelerations in 3 dimensions was acquired using a lightweight wrist-mounted motion sensor. Three features were extracted: (1) Power of higher frequency components of the linear acceleration signal (rest task), as a measure of resting tremor amplitude. (2) Power of higher frequency components of the rotational acceleration signal (pronation/supination task), as a measure of bradykinesia. (3) Standard deviation of the local maxima of the rotational acceleration (pronation/supination task), as a measure of reduction in movement speed and amplitude. These features were used to correctly differentiate trials completed with and without simulated PD symptoms, using an SVM classifier with leave-one-out cross validation accuracy of 95%. These findings suggest it is possible to capture clinical features of PD using motion sensors. Future work in PD patients will examine how these measures correlate with UPDRS evaluations and whether they will be helpful in providing a quick, objective telehealth measure of progression and treatment response that can supplement current tools.

Cardiopulmonary Parameters and Arterial Blood Gases During Etorphine-Medetomidine-Midazolam Immobilization in Free-Ranging Black Rhinoceroses (Diceros bicornis) Undergoing Electro-Ejaculation—A Preliminary Study

Conservation management interventions for the critically endangered black rhinoceros (Diceros bicornis) require immobilization, which offer opportunities for semen collection and cryopreservation to establish genetic reservoirs. In free-ranging rhinoceroses, a combination of the potent opioid etorphine and the tranquilizer azaperone is routinely used for chemical immobilization but is associated with muscle rigidity and severe cardiopulmonary changes. Additionally, azaperone inhibits semen emission. Seven free-ranging, male, sexually mature black rhinoceroses were immobilized with an alternative protocol consisting of 4.5 mg etorphine, 5 mg medetomidine, 50 mg midazolam and 2,500 IU hyaluronidase delivered remotely by darting from a helicopter. During the immobilization, electro-ejaculation was performed with a portable electro-ejaculator, and a species-specific rectal probe. Animals were observed for muscle tremors. Longitudinal changes in respiratory rate, heart rate and peripheral oxyhemoglobin saturation, measured at 5 min intervals, were assessed using a general mixed model. Non-invasive oscillometric blood pressure and arterial blood gas variables were measured at first handling and before reversal and compared using the Wilcoxon rank sum test. All animals were successfully immobilized, showed no muscle tremors, presented with normal heart rates and lactate concentration (&lt;5 mmol/L), recovered uneventfully, but experienced acidemia, hypoxemia and hypercapnia. Induction time and total time in recumbency were 4.2 ± 0.41 and 38.4 ± 6.9 min, respectively. Electro-stimulation commenced after 11.7 ± 3.98 min and completed after 24.3 ± 6.65 min. Semen-rich fractions were successfully collected from six animals. Our observations indicate that etorphine-medetomidine-midazolam provides a promising immobilization protocol for free-ranging black rhinoceroses, that allows for successful electro-ejaculation.

Anti-Parkinsonian Activity of Ganoderma Lucidum in Experimentally Induced Parkinson’s Disease

Background: Parkinson's illness has been proclaimed as the second most neurodegenerative problem on the planet. Ganoderma lucidum is considered as a genuine restorative mushroom. Aim: Our study was directed to assess the antiparkinsonian action of Ganoderma lucidum in rotenone-incited Parkinson’s disease in male Wistar rodents. Methods: The impacts of Ganoderma lucidum were concentrated on catalepsy, muscle rigidity. Results: Ganoderma lucidum fundamentally decreased the expanded length of catalepsy. Rotenone essentially initiated the disturbance of motor neurons as demonstrated by muscle rigidity of muscles and decreased locomotion. Ganoderma lucidum alleviated the disturbance of motor neurons by rotarod execution and locomotor action of the creatures. The exercises of cell reinforcement proteins catalase and superoxide dismutase, and the level of tripeptide glutathione were essentially diminished by rotenone. Besides, rotenone extended the level of lipid peroxidation thing malondialdehyde. Notwithstanding, Ganoderma lucidum supplementation to rotenone-infused rats essentially extended the degrees of superoxide dismutase, catalase, and glutathione, and diminished the level of malondialdehyde Conclusion: Our study firmly supports the notion that Ganoderma lucidum has neuroprotective and antiparkinsonian action.

Umbilical cord blood stem cells transplantation in a patient with severe progressive supranuclear palsy: a case report

Background Progressive supranuclear palsy is a neurodegenerative condition that worsens over time. Given the lack of targeted treatments, patients with severe progressive supranuclear palsy have very low life expectancy. Case presentation We present a case of a 61-year-old Chinese man with severe progressive supranuclear palsy and treated with umbilical cord blood stem cells transplantation. After the umbilical cord blood stem cells therapy, his neurologic symptoms stopped deteriorating, his muscle rigidity was mildly improved, and he remains alive for more than 8 years. Conclusions Umbilical cord blood stem cells transplantation may be an alternative therapy for patients with severe progressive supranuclear palsy.

Respiratory disorders of Parkinson's Disease

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, mainly affecting people over 60 years of age. Patients develop both classic symptoms (tremors, muscle rigidity, bradykinesia and postural instability) and nonclassical symptoms (orthostatic hypotension, neuropsychiatric deficiency, sleep disturbances and respiratory disorders). Thus, patients with PD can have a significantly impaired quality of life, especially when they do not have multi-modality therapeutic follow-up. The respiratory alterations associated with this syndrome are the main cause of mortality in PD. They can be classified as peripheral when caused by disorders of the upper airways or muscles involved in breathing and as central when triggered by functional deficits of important neurons located in the brainstem and involved in respiratory control. Currently, there is little research describing these disorders, and therefore, there is no well-established knowledge about the subject, making the treatment of patients with respiratory symptoms difficult. In this review, the history of the pathology and data about the respiratory changes in PD obtained thus far will be addressed.

Stiffness, Spasms, and Frequent Falls in a 41-Year-Old Man

A 41-year-old man sought care for 3 years of right-sided muscle stiffness. He also had 5- to 10-minute episodes of severe muscle spasms. He noted development of daily episodes of sudden, severe stiffness, often triggered by unexpected stimuli (eg, a touch or loud sound). He started using a walker and stopped driving. He stopped working because of increasing difficulty with mobility and cognition. On neurologic examination, he had a Kokmen Short Test of Mental Status score of 28/38, with points lost for orientation, attention, calculation, and recall. Cranial nerve examination showed bilateral ptosis and hypometric saccadic eye movements. He had normal strength but diffuse rigidity with increased tone, most severe in the right lower extremity. Magnetic resonance imaging of the brain indicated right parietal postoperative changes (post hematoma evacuation). Electroencephalography showed dysrhythmia grade 1 over the right frontotemporal region (above the prior hematoma). Cerebrospinal fluid was inflammatory, with mildly increased protein concentration and supernumerary oligoclonal bands. Movement laboratory evaluation demonstrated an exaggerated startle and abnormal exteroceptive response consistent with central nervous system hyperexcitability. Neural-specific autoantibody testing was positive for glycine receptor α‎1 subunit-immunoglobulin G in both serum and cerebrospinal fluid. He was diagnosed with progressive encephalomyelitis with rigidity and myoclonus with positive glycine receptor α‎1 subunit-immunoglobulin G. Given the immune-mediated cause of progressive encephalomyelitis with rigidity and myoclonus, he was started on intravenous methylprednisolone and concurrent rituximab. The patient markedly improved. His anxiety was still severe, however, and required increased escitalopram and cognitive behavioral therapy to control. He was tapered off intravenous methylprednisolone and maintained on rituximab. His symptoms eventually resolved. He remained stable at 2-year follow-up after initiating immunosuppression. Progressive encephalomyelitis with rigidity and myoclonus is considered a variant of stiff-person syndrome. There is clinical overlap between progressive encephalomyelitis with rigidity and myoclonus and classic stiff-person syndrome, which are both characterized by central nervous system hyperexcitability with exaggerated startle, muscle rigidity, and painful spasms.