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Acta Neurochirurgica Feb 2024Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor, rigidity, and akinesia. According to the literature, the dentato-rubro-thalamic tract...
BACKGROUND
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor, rigidity, and akinesia. According to the literature, the dentato-rubro-thalamic tract (DRTt) is verified target for DBS in essential tremor; however, its role in the treatment of Parkinson's disease is only vaguely described. The aim of our study was to identify the relationship between symptom alleviation in PD patients and the distance of the DBS electrode electric field (EF) to the DRTt.
METHODS
A single-center retrospective analysis of patients (N = 30) with idiopathic Parkinson's disease (PD) who underwent DBS between November 2018 and January 2020 was performed. DRTt and STN were visualized using diffusion-weighted imaging (DWI) and tractography protocol of magnetic resonance (MR). The EF was calculated and compared with STN and course of DRTt. Evaluation of patients before and after surgery was performed with use of UPDRS-III scale. The association between distance from EF to DRTt and clinical outcomes was examined. To confirm the anatomical variation between DRTt and STN observed in tractography, white matter dissection was performed with the Klingler technique on ten human brains.
RESULTS
Patients with EF overlapping STN and DRTt benefited from significant motor symptoms improvement. Anatomical findings confirmed the presence of population differences in variability of the DRTt course and were consistent with the DRTt visualized by MR.
CONCLUSIONS
DRTt proximity to STN, the main target in PD DBS surgery, confirmed by DWI with tractography protocol of MR combined with proper predefined stimulation parameters may improve efficacy of DBS-STN.
Topics: Humans; Subthalamic Nucleus; Parkinson Disease; Deep Brain Stimulation; Retrospective Studies; Thalamus; Treatment Outcome
PubMed: 38403814
DOI: 10.1007/s00701-024-06006-0 -
The American Journal of Cardiology Feb 2024Alcohol septal ablation (ASA) is a well-established procedure for septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy, significant at rest...
Alcohol septal ablation (ASA) is a well-established procedure for septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy, significant at rest or provocable outflow tract gradients, and medically refractory symptoms. This percutaneous approach to relief of obstruction and eventual cardiac remodeling involves the infusion of a small quantity of ethanol into an appropriately targeted septal artery that is feeding the basal septum to create an iatrogenic and controlled focal infarction. Early akinesia is followed by subsequent thinning and remodeling, which widens the outflow tract, reducing or eliminating the obstruction. Historically, the use of ASA was reserved primarily for high-risk surgical candidates; however, more contemporary data suggest similar outcomes in the short-term and long-term safety of the procedure and overall effectiveness in relieving obstructive symptoms when it is performed in broader populations at experienced centers. Therefore, the current guidelines published in 2020 support ASA as a class 1 indication, similar to its open-heart surgical counterpart, surgical myectomy, when no concomitant significant coronary or valve surgical indication exists. This article summarizes contemporary management of patients with hypertrophic cardiomyopathy who were selected for ASA and details procedural methods and outcomes.
Topics: Humans; Treatment Outcome; Heart Septum; Ethanol; Cardiomyopathy, Hypertrophic; Cardiac Surgical Procedures; Ablation Techniques
PubMed: 38368036
DOI: 10.1016/j.amjcard.2023.10.064 -
Neurochemistry International Mar 2024Parkinson's disease (PD) is one of the most prevalent age-related neurodegenerative disorders. Behavioral complexities worsen over time due to progressive dopaminergic...
Parkinson's disease (PD) is one of the most prevalent age-related neurodegenerative disorders. Behavioral complexities worsen over time due to progressive dopaminergic (DArgic) neuronal loss at substantia nigra region of brain. Available treatments typically aim to increase dopamine (DA) levels at striatum. DA is degraded by Monoamine oxidase (MAO), thus dietary phytochemicals with MAO inhibitory properties can contribute to elevate DA levels and reduce the ailment. Characterization of naturally occurring dietary MAO inhibitors is inadequate. Based on available knowledge, we selected different classes of molecules and conducted a screening process to assess their potential as MAO inhibitors. The compounds mostly derived from food sources, broadly belonging to triterpenoids (ursane, oleanane and hopane), alkaloid, polyphenolics, monoterpenoids, alkylbenzene, phenylpropanoid and aromatic alcohol classes. Among all the molecules, highest level of MAO inhibition is offered by α-viniferin, a resveratrol trimer. Cell viability, mitochondrial morphology and reactive oxygen species (ROS) generation remained unaltered by 50 μM α-viniferin treatment in-vitro. Toxicity studies in Drosophila showed unchanged gross neuronal morphology, ROS level, motor activity or long-term survival. α-Viniferin inhibited MAO in mice brain and elevated striatal DA levels. PD-related akinesia and cataleptic behavior were attenuated by α-viniferin due to increase in striatal DA. Our study implies that α-viniferin can be used as an adjunct phytotherapeutic agent for mitigating PD-related behavioral deterioration.
Topics: Mice; Animals; Monoamine Oxidase; Parkinson Disease; Monoamine Oxidase Inhibitors; Reactive Oxygen Species; Dopamine; Benzofurans
PubMed: 38364939
DOI: 10.1016/j.neuint.2024.105698 -
Brazilian Journal of Medical and... 2024This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups:...
This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups: normal saline control and rotenone control were administered saline or rotenone (ROT), respectively, orally; sterubin 10 received ROT + sterubin 10 mg/kg po; and sterubin alone was administered to the test group (10 mg/kg). Rats of the normal saline and sterubin alone groups received sunflower oil injection (sc) daily, 1 h after receiving the treatments cited above, while rats of the other groups received rotenone injection (0.5 mg/kg, sc). The treatment was continued over the course of 28 days daily. On the 29th day, catalepsy and akinesia were assessed. The rats were then euthanized, and the brain was extracted for estimation of endogenous antioxidants (MDA: malondialdehyde, GSH: reduced glutathione, CAT: catalase, SOD: superoxide dismutase), nitrative (nitrite) stress markers, neuroinflammatory cytokines, and neurotransmitter levels and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)). Akinesia and catatonia caused by ROT reduced the levels of endogenous antioxidants (GSH, CAT, and SOD), elevated the MDA level, and altered the levels of nitrites, neurotransmitters, and their metabolites. Sterubin restored the neurobehavioral deficits, oxidative stress, and metabolites of altered neurotransmitters caused by ROT. Results demonstrated the anti-Parkinson's activities of sterubin in ROT-treated rats.
Topics: Rats; Animals; Parkinson Disease; Antioxidants; Rotenone; Saline Solution; Neuroprotective Agents; Oxidative Stress; Neurotransmitter Agents; Superoxide Dismutase; Disease Models, Animal
PubMed: 38359270
DOI: 10.1590/1414-431X2023e12829 -
Prenatal Diagnosis Mar 2024A consanguineous couple was referred at 10 weeks of gestation (WG) for prenatal genetic investigations due to isolated cystic hygroma. Prenatal trio exome sequencing...
Early prenatal diagnosis of causative homozygous variants in ASCC1 in a fetus with cystic hygroma and additional homozygous variants of unknown significance associated with a neurological phenotype not visible in early gestation: Dual diagnosis or not?
A consanguineous couple was referred at 10 weeks of gestation (WG) for prenatal genetic investigations due to isolated cystic hygroma. Prenatal trio exome sequencing identified causative homozygous truncating variants in ASCC1 previously implicated in spinal muscular atrophy with congenital bone fractures. Prenatal manifestations in ASCC1 can usually include hydramnios, fetal hypo-/akinesia, arthrogryposis, contractures and limb deformities, hydrops fetalis and cystic hygroma. An additional truncating variant was identified in CSPP1 associated with Joubert syndrome. Presentations in CSPP1 include cerebellar and brainstem malformations with vermis hypoplasia and molar tooth sign, difficult to visualize in early gestation. A second pregnancy was marked by the recurrence of isolated increased nuchal translucency at 10 + 2 WG. Sanger prenatal diagnosis targeted on ASCC1 and CSPP1 variants showed the presence of the homozygous familial ASCC1 variant. In this case, prenatal exome sequencing analysis is subject to a partial ASCC1 phenotype and an undetectable CSPP1 phenotype at 10 weeks of gestation. As CSPP1 contribution is unclear or speculative to a potentially later in pregnancy or postnatal phenotype, it is mentioned as a variant of uncertain significance. The detection of pathogenic or likely pathogenic variants involved in severe disorders but without phenotype-genotype correlation because the pregnancy is in the early stages or due to prenatally undetectable phenotypes, will encourage the clinical community to define future practices in molecular prenatal reporting.
Topics: Pregnancy; Female; Humans; Lymphangioma, Cystic; Diagnosis, Dual (Psychiatry); Prenatal Diagnosis; Fetus; Phenotype; Carrier Proteins
PubMed: 38342957
DOI: 10.1002/pd.6519 -
Ageing Research Reviews Feb 2024Parkinson's disease (PD) is a progressive neurodegenerative disorder that deals with dopaminergic deficiency in Substantia nigra pars compact (SNpc) region of the brain.... (Review)
Review
Parkinson's disease (PD) is a progressive neurodegenerative disorder that deals with dopaminergic deficiency in Substantia nigra pars compact (SNpc) region of the brain. Dopaminergic deficiency manifests into motor dysfunction. Alpha-synuclein protein aggregation is the source for inception of the pathology. Motor symptoms include rigidity, akinesia, tremor and gait dysfunction. Pre-motor symptoms are also seen in early stage of the disease; however, they are not distinguishable. Lack of early diagnosis in PD pathology poses a major challenge for development of disease modifying therapeutics. Substantial neuronal loss has already been occurred before the clinical manifestations appear and hence, it becomes impossible to halt the disease progression. Current diagnostics are majorly based on the clinical symptoms and thus fail to detect early progression of the disease. Thus, there is need for early diagnosis of PD, for detection of the disease at its inception. This will facilitate the effective use of therapies that halt the progression and will make remission possible. Many novel biomarkers are being developed that include blood-based biomarker, CSF biomarker. Other than that, there are non-invasive techniques that can detect biomarkers. We aim to discuss potential role of these new age biomarkers and their association with PD pathogenesis in this review.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Substantia Nigra; Dopamine; Brain; Biomarkers
PubMed: 38296162
DOI: 10.1016/j.arr.2024.102208 -
Clinical Genetics Jun 2024Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal...
Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%). Postmortem examinations unveiled additional anomalies including facial dysmorphisms, dysplastic skeletal changes, ichthyosis, multiple pterygia, and myopathy, allowing preliminary diagnosis of particular Mendelian disorders in multiple patients. Evaluation of the parents revealed maternal grip myotonia in one family. By exome sequencing and targeted testing, we identified causative variants in ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14, and WASHC5 in 15 families, and one patient with a plausible diagnosis associated with biallelic NEB variants. Three patients received a dual diagnosis. Pathogenic alterations in newly discovered genes or in previously known genes recently linked to new MCC phenotypes were observed in 44% of the cohort. Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes.
Topics: Humans; Female; Male; Arthrogryposis; Phenotype; Fetus; Exome Sequencing; Contracture; Pregnancy; Ultrasonography, Prenatal; Mutation; Abnormalities, Multiple
PubMed: 38278647
DOI: 10.1111/cge.14490 -
Scientific Reports Jan 2024Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group of inherited disorders characterised by...
Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group of inherited disorders characterised by impaired neuromuscular transmission. Most CMS originate from defects in the muscle nicotinic acetylcholine receptor, but the underlying molecular pathogenesis is only poorly understood. Here we show that RNAi-mediated silencing of FADS-related proteins rapsyn and NUP88 in foetal fibroblasts alters organisation of the actin cytoskeleton. We show that fibroblasts from two independent FADS individuals have enhanced and shorter actin stress fibre bundles, alongside with an increased number and size of focal adhesions, with an otherwise normal overall connectivity and integrity of the actin-myosin cytoskeleton network. By proximity ligation assays and bimolecular fluorescence complementation, we show that rapsyn and NUP88 localise nearby adhesion plaques and that they interact with the focal adhesion protein paxillin. Based on these findings we propose that a respective deficiency in rapsyn and NUP88 in FADS alters the regulation of actin dynamics at focal adhesions, and thereby may also plausibly dictate myofibril contraction in skeletal muscle of FADS individuals.
Topics: Humans; Actins; Arthrogryposis; Receptors, Nicotinic; Myasthenic Syndromes, Congenital
PubMed: 38242956
DOI: 10.1038/s41598-023-50615-1