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Nihon Yakurigaku Zasshi. Folia... 2024Parkinson's disease (PD), which has characteristic motor symptoms such as tremor, muscle rigidity, and akinesia, and as the disease progresses, Lewy bodies spread... (Randomized Controlled Trial)
Randomized Controlled Trial
Parkinson's disease (PD), which has characteristic motor symptoms such as tremor, muscle rigidity, and akinesia, and as the disease progresses, Lewy bodies spread throughout the brain, eventually causing Parkinson disease dementia (PDD). The clinical picture of PDD is similar to Dementia with Lewy bodies (DLB) and their pathological features are indistinguishable from each other. More than 80% of PD cases will eventually develop dementia and their prognosis are generally 3 to 4 years from the onset of dementia, regardless of disease duration or age of onset. We found that patients with severe olfactory impairment had lower cognitive function scores, more frequent onset of dementia, brain atrophy, and prominent cerebral metabolic abnormalities in a 3-year longitudinal study (Brain 135:161-169, 2012). This study demonstrated for the first time in the world that olfaction tests are useful in predicting dementia in PD, and similar results have been followed up worldwide. Based on these results, a randomized, double-blind, multicenter comparative study of donepezil in PD with severe olfactory dysfunction (DASH-PD study) was conducted and completed a 4-year follow-up period. The results were recently published showing the efficacy and safety of cholinesterase inhibitors for PD without dementia (eClinicalMedicine 51: 101571, 2022).
Topics: Humans; Parkinson Disease; Lewy Body Disease; Dementia; Longitudinal Studies; Donepezil
PubMed: 38171841
DOI: 10.1254/fpj.23064 -
Journal of Chemical Neuroanatomy Mar 2024Parkinson's Disease (PD) is an age-dependent, incessant, dynamic neurodegenerative illness. In animal models, the administration of the dopaminergic D2 antagonist...
Parkinson's Disease (PD) is an age-dependent, incessant, dynamic neurodegenerative illness. In animal models, the administration of the dopaminergic D2 antagonist Haloperidol (HP) affects the nigrostriatal pathway, inducing catalepsy, a state of immobility like PD, bradykinesia, and akinesia. The present study investigated the neural effects of Icariin (ICA), a flavonoid derived from Herba Epimedii, against HP-induced PD in rats compared to a standard drug levodopa (L-DOPA). Twenty-four adult male rats were divided into 4 groups: the control group treated with vehicle, the 2nd group treated with HP intraperitoneally, the 3rd group treated with the same dose of HP+L-DOPA orally, and the 4th one, treated with the same dose of HP+ICA orally. All the groups were treated for fourteen consecutive days. Two days before the last dose, locomotor activity was assessed in open field and rotarod tasks. At the end of the experiment, the malondialdehyde, nitric oxide (NO), iron, glycogen synthase kinase-3beta (GSK-3β), and tyrosine hydroxylase (TH) contents, glutathione S-transferase, catalase, superoxide dismutase, activities were estimated in the midbrain. Also, cortex and midbrain monoamine contents (norepinephrine, dopamine, and serotonin) were determined. Moreover, the midbrain histopathology was detected in all treated groups. The results suggested that the neuroleptic effect of HP was completely improved by ICA. This improvement occurred by decreasing the neurotoxicity via lowering midbrain lipid peroxidation, NO, GSK-3β contents, increasing antioxidant biomarkers, TH, and recovering the treated groups' cortex and midbrain monoamines contents. In conclusion, this study suggests that ICA is a suitable treatment for Parkinson's induced by HP.
Topics: Rats; Male; Animals; Dopamine; Glycogen Synthase Kinase 3 beta; Levodopa; Haloperidol; Tyrosine 3-Monooxygenase; Parkinsonian Disorders; Parkinson Disease; Disease Models, Animal; Flavonoids
PubMed: 38160784
DOI: 10.1016/j.jchemneu.2023.102385 -
Frontiers in Cardiovascular Medicine 2023The aim was to characterize the electrovectorcardiographic pattern of ventricular aneurysms in ischemic cardiopathy by analyzing the cardiac ventricular repolarization....
The aim was to characterize the electrovectorcardiographic pattern of ventricular aneurysms in ischemic cardiopathy by analyzing the cardiac ventricular repolarization. The medical records of 2,670 individuals were analyzed in this cross-sectional study. A test phase included 33 patients who underwent transthoracic echocardiogram with ultrasonic enhancing agent, electrocardiogram, and vectorcardiogram (aneurysm group - = 22, and akinesia group - = 11). In the validation phase, cardiac magnetic resonance imaging established the left ventricle segmental contractility in 16 patients who underwent electrocardiographic and vectorcardiographic tests (aneurysm group, = 8, and akinesia group, = 8). The variables studied were the presence of the T-wave plus-minus pattern and the T-wave loop anterior-posterior pattern in V2-V4. The diagnostic indices used were sensitivity, specificity, and predictive values, with their respective 95% confidence intervals. During the test and validation phases, the analysis of the presence of the T-wave plus-minus pattern identified the aneurysm group with a sensitivity of 91% vs. 87% and specificity of 91% vs. 87% ( < 0.0001 vs. = 0.01), respectively. Meanwhile, the T-wave loop anterior-posterior pattern evidenced sensitivity of 95% vs. 77% and specificity of 91% vs. 87% ( < 0.0001 vs. = 0.04), respectively. The electrovectorcardiographic parameters showed high accuracy for recognizing left ventricular aneurysms in ischemic heart disease.
PubMed: 38155984
DOI: 10.3389/fcvm.2023.1275194 -
Journal of the Academy of... 2024Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with...
BACKGROUND
Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in the early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis.
METHODS
This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and Neurosurgery of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, and hyperthermia. A logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions.
RESULTS
A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics.
CONCLUSIONS
Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels in patients with anti-NMDAR encephalitis following the administration of antipsychotic medications. Nevertheless, our study does not suggest a causal link between atypical antipsychotics and the onset of these neurological symptoms, as they were equally frequent among the group of patients who did not receive antipsychotic treatment.
Topics: Humans; Neuroleptic Malignant Syndrome; Case-Control Studies; Female; Male; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Adult; Antipsychotic Agents; Middle Aged; Young Adult; Mexico
PubMed: 38151160
DOI: 10.1016/j.jaclp.2023.12.002 -
Prenatal Diagnosis Dec 2023Fetal arthrogryposis is a well-recognised ultrasonographic phenotype, caused by both genetic, maternal and extrinsic factors. When present with fetal growth restriction,...
Fetal arthrogryposis is a well-recognised ultrasonographic phenotype, caused by both genetic, maternal and extrinsic factors. When present with fetal growth restriction, pulmonary hypoplasia and multiple joint contractures, it is often referred to as fetal akinesia deformation sequence (FADS). Historically, elucidating genetic causes of arthryogryposis/FADS has been challenging; there are now more than 150 genes known to cause arthrogryposis through myopathic, neuromuscular and metabolic pathways affecting fetal movement. FADS is associated with over 400 medical conditions making prenatal diagnosis challenging. Here we present a case of FADS diagnosed at 19 weeks gestation with progression to severe fetal hydrops and stillbirth at 26-weeks gestation. Initial investigations including combined first trimester screening, TORCH (infection) screen and chromosomal microarray were normal. Trio whole exome sequencing (WES) detected compound heterozygous likely pathogenic CACNA1S gene variants associated with autosomal dominant (AD) and autosomal recessive (AR) congenital myopathy and FADS. To our knowledge, this is the first prenatal diagnosis of this condition.
Topics: Pregnancy; Female; Humans; Arthrogryposis; Stillbirth; Prenatal Diagnosis; Edema; Calcium Channels, L-Type
PubMed: 38111203
DOI: 10.1002/pd.6471 -
Frontiers in Public Health 2023This study aims to provide a comprehensive analysis of clinical and epidemiological data related to Chronic Chagas Cardiomyopathy (CCC) in the Amazon region of Brazil. (Review)
Review
OBJECTIVES
This study aims to provide a comprehensive analysis of clinical and epidemiological data related to Chronic Chagas Cardiomyopathy (CCC) in the Amazon region of Brazil.
METHODS
A review of observational, retrospective, and cross-sectional studies related to Chagas Disease in the Amazon region of Brazil was conducted, and a case series addressing CCC in patients treated at the FMT-HVD outpatient clinic, a reference center for Chagas disease in Brazil, was carried out.
RESULTS
Clinical characteristics of 55 patients from the Amazon region with CCC were described. The most common electrocardiographic alteration observed was abnormal ventricular repolarization (AVR), present in 40% of cases. The most common echocardiographic finding was left ventricular systolic dysfunction (49%), followed by akinesia or hypokinesia of the inferior and/or inferolateral walls (38.1%) and the presence of an apical aneurysm (32.7%).
CONCLUSIONS
Overall, this study demonstrates that CCC in the Amazon region presents clinical characteristics and severity that are similar to those observed in other regions. However, certain peculiarities, such as the frequency of right bundle branch block (RBBB) and anterior and septal involvement during the acute phase, require additional investigation to better comprehend the disease in the region. Overall, the study provides crucial clinical insights for the diagnosis and treatment of CCC in the Amazon region.
Topics: Humans; Chagas Cardiomyopathy; Brazil; Retrospective Studies; Cross-Sectional Studies; Chagas Disease
PubMed: 38089032
DOI: 10.3389/fpubh.2023.1284639 -
Frontiers in Aging Neuroscience 2023Impaired bed mobility (IBM) is a symptom characteristic of patients having difficulty intentionally moving their bodies during nighttime sleep. IBM is one of the most... (Review)
Review
Impaired bed mobility (IBM) is a symptom characteristic of patients having difficulty intentionally moving their bodies during nighttime sleep. IBM is one of the most common nocturnal symptoms of Parkinson's disease (PD) and may lead to extreme pain and even death; it also increases the burden on the patients' caregivers. In this systematic review, we included 19 studies involving a total of 1,407 patients with PD to observe the causes, assessment methods, and treatment options for IBM. We conclude that the extent of IBM is positively correlated with the severity of symptoms such as disease duration, dyskinesia and decreased sleep quality in patients with PD, and the evidence implies that IBM may be able to serve as a prodromal feature in the development of PD. IBM probably results from low nocturnal dopamine concentrations, reduced function of the spinal tract, torque problems in the muscles, and aging. Therefore, treatment is mostly based on continuously increasing the patient's nocturnal dopamine concentration, while deep brain stimulation (DBS) also has a mitigating effect on IBM. Both scales and sensors are commonly used to measure the severity of IBM, the wearable device monitoring and scales being updated makes measurements easier and more accurate. The future of the advancement in this field lies in the use of more family-oriented devices (such as smart phones or watches and bracelets, etc.) to monitor IBM's symptoms and select the appropriate therapeutic treatment according to the severity of the symptoms to relieve patients' suffering.
PubMed: 38076536
DOI: 10.3389/fnagi.2023.1264143 -
European Journal of Obstetrics,... Jan 2024To present the prenatal features and postnatal outcomes of pregnancies with fetal nemaline myopathy (NM).
OBJECTIVE
To present the prenatal features and postnatal outcomes of pregnancies with fetal nemaline myopathy (NM).
STUDY DESIGN
This was a retrospective study of nine cases with NM diagnosed by prenatal or postnatal clinical features and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, exome sequencing (ES) results, and pregnancy outcomes.
RESULTS
All of the nine cases were detected to have NM-causing variants, involving NEB gene in 2 cases, ACTA1 in 3 cases, KLHL40 in 3 cases, and TPM2 in 1 case. Almost all (8/9) had normal first-trimester ultrasound scans except one who had an increased nuchal translucency. Seven (7/9) cases had second-trimester abnormal ultrasounds with fetal akinesia and/or extremity anomalies. Two (2/9) had only third-trimester abnormal ultrasounds with fetal akinesia and polyhydramnios, with one combined with fetal growth restriction. Four pregnancies with a positive prenatal ES were terminated, while five having not receiving prenatal ES continued to term. Only one infant survived 1 year old, and four passed away within 12 months.
CONCLUSION
Prenatal ultrasound can detect clues that lead to the diagnosis of NM, such as reduced or absent fetal movements, polyhydramnios and extremity anomalies.
Topics: Pregnancy; Female; Humans; Infant; Myopathies, Nemaline; Retrospective Studies; Polyhydramnios; Ultrasonography, Prenatal; Pregnancy Outcome; Muscle Proteins
PubMed: 38071834
DOI: 10.1016/j.ejogrb.2023.12.005 -
Experimental Brain Research Feb 2024Depression is a common non-motor symptom in Parkinson's disease (PD) that includes anhedonia and impacts quality of life but is not effectively treated with conventional...
Depression is a common non-motor symptom in Parkinson's disease (PD) that includes anhedonia and impacts quality of life but is not effectively treated with conventional antidepressants clinically. Vagus nerve stimulation improves treatment-resistant depression in the general population, but research about its antidepressant efficacy in PD is limited. Here, we administered peripheral non-invasive focused ultrasound to hemiparkinsonian ('PD') and non-parkinsonian (sham) rats to mimic vagus nerve stimulation and assessed its antidepressant-like efficacy. Following 6-hydroxydopamine (6-OHDA) lesion, akinesia-like immobility was assessed in the limb-use asymmetry test, and despair- and anhedonic-like behaviors were evaluated in the forced swim test and sucrose preference test, respectively. After, tyrosine hydroxylase immuno-staining was employed to visualize and quantify dopaminergic degeneration in the substantia nigra pars compacta, ventral tegmental area, and striatum. We found that PD rats exhibited akinesia-like immobility and > 90% reduction in tyrosine hydroxylase immuno-staining ipsilateral to the lesioned side. PD rats also demonstrated anhedonic-like behavior in the sucrose preference test compared to sham rats. No 6-OHDA lesion effect on immobility in the forced swim test limited conclusions about the efficacy of ultrasound on despair-like behavior. However, ultrasound improved anhedonic-like behavior in PD rats and this efficacy was sustained through the end of the 1-week recovery period. The greatest number of animals demonstrating increased sucrose preference was in the PD group receiving ultrasound. Our findings here are the first to posit that peripheral non-invasive focused ultrasound to the celiac plexus may improve anhedonia in PD with further investigation needed to reveal its potential for clinical applicability.
Topics: Humans; Rats; Animals; Anhedonia; Rats, Wistar; Tyrosine 3-Monooxygenase; Quality of Life; Parkinson Disease; Oxidopamine; Antidepressive Agents; Sucrose; Disease Models, Animal
PubMed: 38059986
DOI: 10.1007/s00221-023-06750-2 -
Frontiers in Neuroscience 2023
PubMed: 38033545
DOI: 10.3389/fnins.2023.1322091