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Journal of Medical Genetics Sep 2023Titin truncating variants (TTNtvs) have been associated with several forms of myopathies and/or cardiomyopathies. In homozygosity or in compound heterozygosity, they...
BACKGROUND
Titin truncating variants (TTNtvs) have been associated with several forms of myopathies and/or cardiomyopathies. In homozygosity or in compound heterozygosity, they cause a wide spectrum of recessive phenotypes with a congenital or childhood onset. Most recessive phenotypes showing a congenital or childhood onset have been described in subjects carrying biallelic TTNtv in specific exons. Often karyotype or chromosomal microarray analyses are the only tests performed when prenatal anomalies are identified. Thereby, many cases caused by defects might be missed in the diagnostic evaluations. In this study, we aimed to dissect the most severe end of the titinopathies spectrum.
METHODS
We performed a retrospective study analysing an international cohort of 93 published and 10 unpublished cases carrying biallelic TTNtv.
RESULTS
We identified recurrent clinical features showing a significant correlation with the genotype, including fetal akinesia (up to 62%), arthrogryposis (up to 85%), facial dysmorphisms (up to 73%), joint (up to 17%), bone (up to 22%) and heart anomalies (up to 27%) resembling complex, syndromic phenotypes.
CONCLUSION
We suggest to be carefully evaluated in any diagnostic process involving patients with these prenatal signs. This step will be essential to improve diagnostic performance, expand our knowledge and optimise prenatal genetic counselling.
Topics: Female; Humans; Pregnancy; Abortion, Habitual; Connectin; Retrospective Studies; Muscle, Skeletal; Myocardium
PubMed: 36977548
DOI: 10.1136/jmg-2022-109018 -
Wiener Medizinische Wochenschrift (1946) Apr 2024Huntington's disease is a rare autosomal dominant disorder presenting with chorea, rigidity, hypo-/akinesia, cognitive decline, and psychiatric disturbances. Numerous... (Review)
Review
Huntington's disease is a rare autosomal dominant disorder presenting with chorea, rigidity, hypo-/akinesia, cognitive decline, and psychiatric disturbances. Numerous risk factors have been defined in the onset of this disease. However, the number of CAG repeats in the genes are the most crucial factor rendering patients susceptible to the disease. Studies have shown significant differences in onset and disease presentation among the sexes, which prompts analysis of the impact of different sexes on disease etiology and progression. This article therefore discusses the evidence-based role of sex in aspects of symptomatology, pathogenesis, biomarkers, progression, and prognosis of Huntington's disease, with a secondary review of sex-linked differences in Alzheimer's and Parkinson's disease.
Topics: Humans; Huntington Disease; Prognosis
PubMed: 35723821
DOI: 10.1007/s10354-022-00941-2 -
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 -
Inflammopharmacology Oct 2023Cerium oxide nanoparticles (CONPs), owing to their radical scavenging property, have recently emerged as a therapeutic candidate for oxidative stress-mediated...
Cerium oxide nanoparticles (CONPs), owing to their radical scavenging property, have recently emerged as a therapeutic candidate for oxidative stress-mediated neurological diseases. However, oral and intravenous administration of CONPs is limited due to their poor physicochemical characteristics, low bioavailability, rapid systemic clearance, poor blood-brain penetration and dose-dependent toxicity. To overcome these challenges, we developed intranasal CONPs and evaluated their potential in the experimental PD model. CONPs were prepared by homogenous precipitation using tween 80 as a stabilizer and methanol/water as solvent. The optimization was done using Central Composite Design (CCD). The CONPs synthesis was confirmed by UV and FTIR. The optimized CONPs were small-sized (105.1 ± 5.78 nm), spherical (TEM), uniform (PDI, 0.119 ± 0.006) and stable (ZP, -22.7 ± 1.02 mV). Energy-dispersive X-ray analysis showed characteristic signals of Ce in developed CONPs. The X-ray diffraction pattern described the cubic fluorite structure and nano-crystalline nature of CONPs. The CONP anti-oxidant activity was found to be 93.60 ± 0.32% at 25 µg/mL concentration. Finally, motor manifestation studies like the forced swim test, locomotor test, akinesia, catalepsy, and muscle coordination test were conducted to assess the motor dysfunctions and behavioral activity in all four animal groups. Results of the in vivo motor manifestation studies in the haloperidol-induced PD rat model showed that co-administration of intranasal CONPs along with a half dose of levodopa resulted in significant protection, and results were significantly different from the untreated group but not significantly different from the healthy group. In conclusion, intranasal CONPs can be useful in ameliorating oxidative stress through their antioxidant effect and could be prospective therapeutics for the treatment of motor manifestations in Parkinson's disease.
Topics: Rats; Animals; Haloperidol; Nanoparticles; Oxidative Stress; Parkinsonian Disorders
PubMed: 37432554
DOI: 10.1007/s10787-023-01274-1 -
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 -
Frontiers in Neuroscience 2023Paraquat (1,1'-dimethyl-4-4'-bipyridinium dichloride) exposure is well-established as a neurotoxic agent capable of causing neurological deficits in offspring. This...
BACKGROUND
Paraquat (1,1'-dimethyl-4-4'-bipyridinium dichloride) exposure is well-established as a neurotoxic agent capable of causing neurological deficits in offspring. This study aimed to investigate therapeutic effects of L. aqueous extract (AU) against paraquat (PQ) exposure.
METHODS
For that the phytoconstituents of AU was determined by LC/MS, and then its antioxidant potential was assessed by DPPH and ABTS assays. The assessment included its impact on cell viability and mitochondrial metabolism using N27 dopaminergic cells. Additionally, we evaluated the effects of prenatal PQ exposure on motor coordination, dopamine levels, trace element levels, and total antioxidant capacity (TAC) in rat progeny.
RESULTS
The phytochemical profile of AU extract revealed the presence of 35 compounds, primarily phenolic and organic acids, and flavonoids. This accounted for its strong antioxidant activities against DPPH and ABTS radicals, surpassing the activities of vitamin C. Our findings demonstrated that AU effectively inhibited PQ-induced loss of N27 rat dopaminergic neural cells and significantly enhanced their mitochondrial respiration. Furthermore, daily post-treatment with AU during the 21 days of the rat's pregnancy alleviated PQ-induced motor deficits and akinesia in rat progeny. These effects inhibited dopamine depletion and reduced iron levels in the striatal tissues. The observed outcomes appeared to be mediated by the robust antioxidant activity of AU, effectively counteracting the PQ-induced decrease in TAC in the blood plasma of rat progeny. These effects could be attributed to the bioactive compounds present in AU, including phenolic acids such as gallic acid and flavonoids such as quercetin, rutin, apigenin, glucuronide, and kaempferol, all known for their potent antioxidant capacity.
DISCUSSION
In conclusion, this preclinical study provided the first evidence of the therapeutic potential of AU extract against PQ-induced neurotoxicity. These findings emphasize the need for further exploration of the clinical applicability of AU in mitigating neurotoxin-induced brain damage.
PubMed: 37901424
DOI: 10.3389/fnins.2023.1244603 -
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 -
Journal of Neurosurgery Aug 2023Surgical resection of gliomas involving the supplementary motor area (SMA) frequently results in SMA syndrome, a symptom complex characterized by transient akinesia and...
OBJECTIVE
Surgical resection of gliomas involving the supplementary motor area (SMA) frequently results in SMA syndrome, a symptom complex characterized by transient akinesia and mutism. Because the factors influencing patient functional outcomes after surgery remain elusive, the authors investigated network-based predictors in a multicentric cohort of glioma patients.
METHODS
The participants were 50 patients treated for glioma located in the SMA at one of the three centers participating in the study. Postoperative functional outcomes (motor deficits, mutism) and duration of symptoms were assessed during hospitalization. Long-term outcome was assessed 3 months after surgery. MRI-based lesion-symptom mapping was performed to estimate the severity of gray matter damage and white matter disconnection.
RESULTS
The median duration of acute symptoms was 3 days (range 1-42 days). Long-term deficits involving fine motor movements and speech were found at follow-up in 27 patients (54%). Disconnection of the central callosal fibers was associated with prolonged acute symptoms (p < 0.05). Postoperative mutism was significantly related to disconnection severity of the left frontopontine tract, frontal aslant tract, cingulum, and corticostriatal tract (p < 0.05). Disconnection of midposterior callosal fibers and lesion loads within the left medial Brodmann area 4 were associated with long-term motor deficits (p < 0.05).
CONCLUSIONS
This study provides evidence for the pathophysiology and predictive factors of postoperative SMA syndrome by demonstrating the relation of the disconnection of callosal fibers with prolonged symptom duration (central segment) and long-term motor deficits (midposterior segment). These data may be useful for presurgical risk assessment and adequate consultation for patients prior to undergoing resection of glioma located within the SMA region.
Topics: Humans; Glioma; Male; Female; Brain Neoplasms; Adult; Middle Aged; Postoperative Complications; Motor Cortex; Recovery of Function; Young Adult; Aged; Corpus Callosum; Mutism; Magnetic Resonance Imaging; Adolescent; Treatment Outcome; Syndrome
PubMed: 36461815
DOI: 10.3171/2022.10.JNS221303 -
Medicina (Kaunas, Lithuania) Apr 2024This study delves into the multifaceted approaches to treating Parkinson's disease (PD), a neurodegenerative disorder primarily affecting motor function but also... (Review)
Review
This study delves into the multifaceted approaches to treating Parkinson's disease (PD), a neurodegenerative disorder primarily affecting motor function but also manifesting in a variety of symptoms that vary greatly among individuals. The complexity of PD symptoms necessitates a comprehensive treatment strategy that integrates surgical interventions, pharmacotherapy, and physical therapy to tailor to the unique needs of each patient. Surgical options, such as deep brain stimulation (DBS), have been pivotal for patients not responding adequately to medication, offering significant symptom relief. Pharmacotherapy remains a cornerstone of PD management, utilizing drugs like levodopa, dopamine agonists, and others to manage symptoms and, in some cases, slow down disease progression. However, these treatments often lead to complications over time, such as motor fluctuations and dyskinesias, highlighting the need for precise dosage adjustments and sometimes combination therapies to optimize patient outcomes. Physical therapy plays a critical role in addressing the motor symptoms of PD, including bradykinesia, muscle rigidity, tremors, postural instability, and akinesia. PT techniques are tailored to improve mobility, balance, strength, and overall quality of life. Strategies such as gait and balance training, strengthening exercises, stretching, and functional training are employed to mitigate symptoms and enhance functional independence. Specialized approaches like proprioceptive neuromuscular facilitation (PNF), the Bobath concept, and the use of assistive devices are also integral to the rehabilitation process, aimed at improving patients' ability to perform daily activities and reducing the risk of falls. Innovations in technology have introduced robotic-assisted gait training (RAGT) and other assistive devices, offering new possibilities for patient care. These tools provide targeted support and feedback, allowing for more intensive and personalized rehabilitation sessions. Despite these advancements, high costs and accessibility issues remain challenges that need addressing. The inclusion of exercise and activity beyond structured PT sessions is encouraged, with evidence suggesting that regular physical activity can have neuroprotective effects, potentially slowing disease progression. Activities such as treadmill walking, cycling, and aquatic exercises not only improve physical symptoms but also contribute to emotional well-being and social interactions. In conclusion, treating PD requires a holistic approach that combines medical, surgical, and therapeutic strategies. While there is no cure, the goal is to maximize patients' functional abilities and quality of life through personalized treatment plans. This integrated approach, along with ongoing research and development of new therapies, offers hope for improving the management of PD and the lives of those affected by this challenging disease.
Topics: Humans; Parkinson Disease; Physical Therapy Modalities; Independent Living; Gait; Deep Brain Stimulation; Quality of Life; Exercise Therapy
PubMed: 38792894
DOI: 10.3390/medicina60050711