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Clinical and Experimental Emergency... Jan 2024We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest.
OBJECTIVES
We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest.
METHODS
We performed a prospective, randomized controlled pilot trial, randomizing subjects to amantadine 100mg twice daily or placebo for up to 7 days. The study drug was administered between 72-120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category (CPC) at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher's exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests.
RESULTS
After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), 7 in the amantadine arm and 7 in the placebo arm. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.57%) and placebo groups (n=3, 42.86%) (p = 1.00). There were no differences in secondary outcomes. Study medication was stopped in three (21%) subjects. Adverse events included a recurrence of seizures (n=2; 14%), both of which occurred in the placebo arm.
CONCLUSION
We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.
PubMed: 38286499
DOI: 10.15441/ceem.23.158 -
Planta Medica Apr 2024Extracellular senile plaques and intraneuronal neurofibrillary tangles are two devastating brain proteinopathies that are indicative of Alzheimer's disease, the most...
Extracellular senile plaques and intraneuronal neurofibrillary tangles are two devastating brain proteinopathies that are indicative of Alzheimer's disease, the most prevalent type of dementia. Currently, no effective medications are available to stop or reverse Alzheimer's disease. extract, commonly referred to as EGb 761, is a natural product made from the leaves of the tree. It has long been demonstrated to have therapeutic benefits in Alzheimer's disease. The current study assessed the beneficial effects of EGb 761 against Alzheimer's disease in comparison with memantine, a standard treatment for Alzheimer's disease. The scopolamine-heavy metals mixture rat Alzheimer's disease model is a newly created model to study the effects of EGb 761 oral therapy on cognitive performance and other Alzheimer's disease-like changes over a 28-day experimental period. This new Alzheimer's disease model provides better criteria for Alzheimer's disease hallmarks than the conventional scopolamine model. The EGb 761 reversed memory and learning deficits induced by the scopolamine-heavy metals mixture. These outcomes were linked to a more pronounced inhibitory effect on acetylcholinesterase, caspase-3, hippocampal amyloid-beta protein (A1 - 42), phosphorylated tau protein counts, and proinflammatory cytokines (tumor necrosis factor- and interleukin-1) compared to the memantine-treated group. Furthermore, EGb 761 treatment considerably reduced lipid peroxidation (malondialdehyde) and improved reduced glutathione levels compared to memantine. Our results suggest EGb 761's potential in treating central nervous system disorders. It's a promising candidate for future Alzheimer's disease therapeutic exploration. This study also highlights the need for future research to focus on the positive benefits of herbal medicines.
Topics: Animals; Rats; Alzheimer Disease; Memantine; Ginkgo biloba; Acetylcholinesterase; Plant Extracts; Cognitive Dysfunction; Metals, Heavy; Scopolamine Derivatives; Ginkgo Extract
PubMed: 38286405
DOI: 10.1055/a-2245-3624 -
Mini Reviews in Medicinal Chemistry Jan 2024Neurodegenerative disorders pose a significant challenge to global healthcare systems due to their progressive nature and the resulting loss of neuronal cells and...
Neurodegenerative disorders pose a significant challenge to global healthcare systems due to their progressive nature and the resulting loss of neuronal cells and functions. Excitotoxicity, characterized by calcium overload, plays a critical role in the pathophysiology of these disorders. In this review article, we explore the involvement of calcium dysregulation in neurodegeneration and neurodegenerative disorders. A promising therapeutic strategy to counter calcium dysregulation involves the use of calcium modulators, particularly polycyclic cage compounds. These compounds, structurally related to amantadine and memantine, exhibit neuroprotective properties by attenuating calcium influx into neuronal cells. Notably, the pentacycloundecylamine NGP1-01, a cage-like structure, has shown efficacy in inhibiting both N-methyl-D-aspartate (NMDA) receptors and voltage-gated calcium channels (VGCCs), making it a potential candidate for neuroprotection against excitotoxic-induced neurodegenerative disorders. The structure-activity relationship of polycyclic cage compounds is discussed in detail, highlighting their calcium-inhibitory activities. Various closed, open, and rearranged cage compounds have demonstrated inhibitory effects on calcium influx through NMDA receptors and VGCCs. Additionally, these compounds have exhibited neuroprotective properties, including free radical scavenging, attenuation of neurotoxicities, and reduction of neuroinflammation. Although the calcium modulatory activities of polycyclic cage compounds have been extensively studied, apart from amantadine and memantine, none have undergone clinical trials. Further in vitro and in vivo studies and subsequent clinical trials are required to establish the efficacy and safety of these compounds. The development of polycyclic cages as potential multifunctional agents for treating complex neurodegenerative diseases holds great promise.
PubMed: 38275027
DOI: 10.2174/0113895575273868231128104121 -
Journal of Clinical Medicine Jan 2024Traumatic brain injury (TBI) is one of the most common causes of death and an important burden to the worldwide healthcare system and society. There is a lack of...
INTRODUCTION
Traumatic brain injury (TBI) is one of the most common causes of death and an important burden to the worldwide healthcare system and society. There is a lack of guidelines for types of monitoring or neuroprotective therapy. The aim of this pilot study was to assess its feasibility and, furthermore, to evaluate the impact of Cerebrolysin on the following clinical outcomes: length of stay, Glasgow Outcome Scale (GOS) and mortality.
METHODS
A cohort of 56 patients was included in this non-randomised, real-time, pre-post-interventional study. The patients were assessed with the Glasgow Coma Scale (GCS) and divided into two groups: severe (GCS < 8) and non-severe (GCS > 8). After the radiological examination (CT scan), the patients were qualified for an immediate neurosurgical procedure if needed. The patients were admitted to the intensive care unit, where a standardised protocol for TBI treatment was implemented. Additional neuromonitoring was applied.
RESULTS
There were 56 patients (19 females; 33.9%), of which 41 were considered severe cases; the patients were allocated to the Cerebrolysin ( = 25) or control groups ( = 31). In a generalised linear model (GLM) approach, the use of Cerebrolysin was associated with a decrease in the probability of death in non-severe patients (by 0.333 (standard error (SE) = 0.157, = 0.034)) but not in severe patients (estimate (Est.) = -0.115, SE = 0.127, = 0.364). Patients who received Cerebrolysin and who were neuromonitored had favourable outcomes and better survival rates.
CONCLUSIONS
A multimodal treatment approach with monitoring and Cerebrolysin may have a beneficial effect on patients with less severe TBIs; however, the present study has multiple limitations, and further research is needed.
PubMed: 38256487
DOI: 10.3390/jcm13020353 -
Neuropediatrics Apr 2024The risk factors for respiratory insufficiency in children with Guillain-Barré syndrome (GBS) are poorly known. This study aimed to investigate the factors associated...
OBJECTIVE
The risk factors for respiratory insufficiency in children with Guillain-Barré syndrome (GBS) are poorly known. This study aimed to investigate the factors associated with respiratory insufficiency in children with GBS.
METHODS
This retrospective study included children diagnosed with GBS by pediatric neurologists and admitted at the Wuhan Children's Hospital and other hospitals from January 2013 to October 2022. The patients were divided into the respiratory insufficiency and nonrespiratory insufficiency groups according to whether they received assist breathing during treatment.
RESULTS
The median (interquartile range) age of onset of 103 patients were 5 (3.1-8.5) years, 69 (67%) were male, and 64 (62.1%) had a history of precursor infection. Compared with the nonrespiratory insufficiency group, the respiratory insufficiency group showed more facial and/or bulbar weakness ( = 0.002), a higher Hughes Functional Grading Scale (HFGS) at admission ( < 0.001), and a shorter onset-to-admission interval ( = 0.017). Compared with the acute motor axonal neuropathy (AMAN) subtype, the acute inflammatory demyelinating polyneuropathy (AIDP) subtype showed longer days from onset to lumbar ( = 0.000), lower HFGS at admission ( = 0.04), longer onset-to-admission interval ( = 0.001), and more cranial nerve involvement ( = 0.04). The incidence of respiratory insufficiency between AIDP and AMAN showed no statistical difference ( > 0.05).
CONCLUSION
In conclusion, facial and/or bulbar weakness, HFGS at admission, and onset-to-admission interval were associated with respiratory insufficiency and might be useful prognostic markers in children with GBS.
Topics: Child; Humans; Male; Child, Preschool; Female; Guillain-Barre Syndrome; Retrospective Studies; Hospitalization; Respiratory Insufficiency; Amantadine
PubMed: 38253279
DOI: 10.1055/s-0043-1777767 -
Biosensors Dec 2023Amantadine (AMD) is an antiviral drug that is prohibited for use in livestock and poultry. In this study, carboxyl-modified magnetic nanoparticles (MNPs) were...
Amantadine (AMD) is an antiviral drug that is prohibited for use in livestock and poultry. In this study, carboxyl-modified magnetic nanoparticles (MNPs) were synthesized using the solvothermal method in one step with harmless and inexpensive regents, and they were used to label monoclonal antibodies (mAbs) of AMD in microwells with electrostatic adsorption. Then, a magnetic immunochromatography assay (MICA) method was successfully established. Under optimal conditions, the MICA showed a good performance, with a linear range of 0.2~10.0 µg/L. The limit of detection (LOD) was 0.068 µg/L with the instrument, and the visual LOD (vLOD) was 0.5 µg/L. There was no cross-reaction with rimantadine and ribavirin. The vLOD in real samples was 1.0 µg/kg. The developed MICA has the advantages of convenience, speed, and sensitivity, which make it suitable for the on-site rapid detection of AMD residues in chicken tissues and eggs.
Topics: Amantadine; Antiviral Agents; Chromatography, Affinity; Nanoparticles; Static Electricity
PubMed: 38248400
DOI: 10.3390/bios14010023 -
The American Journal of Geriatric... Jun 2024To examine whether initiation of an antidepressant is associated with the development of impulse control disorder (ICD) in patients with Parkinson's disease (PD). (Observational Study)
Observational Study
OBJECTIVES
To examine whether initiation of an antidepressant is associated with the development of impulse control disorder (ICD) in patients with Parkinson's disease (PD).
DESIGN
We performed a retrospective analysis utilizing data from the Parkinson's Progression Markers Initiative (PPMI). Two-sample Mann-Whitney tests were used for comparison of continuous variables and Pearson χ tests were used for categorical variables. Kaplan-Meier survival analysis and cox proportional hazards regression analysis was used to assess the hazard of ICD with antidepressant exposure.
SETTING
The PPMI is a multicenter observational study of early PD with 52 sites throughout North America, Europe, and Africa.
PARTICIPANTS
Participants in the current study were those in the PPMI PD cohort with a primary diagnosis of idiopathic PD.
MEASUREMENTS
The presence of ICD was captured using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). Antidepressant use was defined based on medication logs for each participant. Depressive symptoms were captured using the Geriatric Depression Scale (GDS).
RESULTS
A total of 1,045 individuals were included in the final analysis. There was a significant increase in the probability of ICD in those exposed to serotonergic antidepressants compared to those not exposed (Log-rank p <0.001). Serotonergic antidepressant use was associated with a hazard ratio for ICD of 1.4 (95% CI 1.0-1.8, z-value 2.1, p = 0.04) after adjusting for dopamine agonist use, depression, bupropion use, MAOI-B use, amantadine use, LEDD, disease duration, sex, and age.
CONCLUSIONS
Serotonergic antidepressant use appears to be temporally associated with ICD in patients with PD.
Topics: Humans; Parkinson Disease; Disruptive, Impulse Control, and Conduct Disorders; Male; Female; Aged; Retrospective Studies; Antidepressive Agents; Middle Aged; Depression; Proportional Hazards Models
PubMed: 38238235
DOI: 10.1016/j.jagp.2023.12.024 -
Scientific Reports Jan 2024Many COVID-19 survivors experience lingering post-COVID-19 symptoms, notably chronic fatigue persisting for months after the acute phase. Despite its prevalence, limited... (Randomized Controlled Trial)
Randomized Controlled Trial
Many COVID-19 survivors experience lingering post-COVID-19 symptoms, notably chronic fatigue persisting for months after the acute phase. Despite its prevalence, limited research has explored effective treatments for post-COVID-19 fatigue. This randomized controlled clinical trial assessed the impact of Amantadine on patients with post-COVID-19 fatigue. The intervention group received Amantadine for two weeks, while the control group received no treatment. Fatigue levels were assessed using the Visual Analog Fatigue Scale (VAFS) and Fatigue Severity Scale (FSS) questionnaires before and after the trial. At the study's onset, VAFS mean scores were 7.90 ± 0.60 in the intervention group and 7.34 ± 0.58 in the control group (P-value = 0.087). After two weeks, intervention group scores dropped to 3.37 ± 0.44, significantly lower than the control group's 5.97 ± 0.29 (P-value < 0.001). Similarly, FSS mean scores at the trial's commencement were 53.10 ± 5.96 in the intervention group and 50.38 ± 4.88 in the control group (P-value = 0.053). At the trial's end, intervention group scores decreased to 28.40 ± 2.42, markedly lower than the control group's 42.59 ± 1.50 (P-value < 0.001). In this study, we report the safety, tolerability, and substantial fatigue-relieving effects of Amantadine in post-COVID-19 fatigue. The intervention demonstrates a statistically significant reduction in fatigue levels, suggesting Amantadine's potential as an effective treatment for this persistent condition.
Topics: Humans; Multiple Sclerosis; COVID-19; Amantadine; Treatment Outcome; Surveys and Questionnaires
PubMed: 38228731
DOI: 10.1038/s41598-024-51904-z -
BMJ Case Reports Jan 2024
Topics: Humans; Livedo Reticularis; Amantadine; Parkinson Disease; Antiparkinson Agents
PubMed: 38216170
DOI: 10.1136/bcr-2023-257492 -
Qatar Medical Journal 2023Parkinsonism-hyperpyrexia syndrome (PHS) is a potentially life-threatening condition that occurs due to the abrupt withdrawal or significant dose reduction of...
BACKGROUND
Parkinsonism-hyperpyrexia syndrome (PHS) is a potentially life-threatening condition that occurs due to the abrupt withdrawal or significant dose reduction of antiparkinsonian medications. It presents similarly to neuroleptic malignant syndrome (NMS) and is characterized by severe rigidity, fever, autonomic instability, and altered mental status.
CASE
A 62-year-old male with a 10-year history of Parkinson's disease (PD) underwent laparoscopic mesh repair for a left-sided diaphragmatic and large hiatus hernia. His antiparkinsonian medications included levodopa/carbidopa, amantadine, pramipexole, and benzhexol. Medications were withheld as part of the nil per os (NPO) status. Postoperatively, he developed withdrawal features, including tremors, difficulty speaking, tachycardia, hypertension, fever, and sweating. PHS, resulting from the withdrawal of antiparkinsonian medications, was diagnosed. The patient was transferred to the intensive care unit (ICU), intubated, and his antiparkinsonian medications were reintroduced. The patient's condition improved gradually, and he was discharged home on the 15th postoperative day.
DISCUSSION
The abrupt discontinuation of antiparkinsonian medications precipitated PHS in our patient. Recognizing the clinical picture of PHS and differentiating it from other possible conditions, such as neuroleptic malignant syndrome and malignant hyperthermia, is pivotal. Management involves resuming medications and providing supportive care. Early recognition and prompt reintroduction of the antiparkinsonian medications are essential for the patient's recovery.
CONCLUSION
PHS is a rare but potentially life-threatening condition that occurs due to the withdrawal of antiparkinsonian medications, leading to an acute hypodopaminergic state. Our case emphasizes the importance of careful perioperative management of antiparkinsonian medications and early recognition and management of withdrawal symptoms in patients with Parkinson's disease undergoing surgery.
PubMed: 38204562
DOI: 10.5339/qmj.2023.34