-
Cell Stem Cell May 2024Autonomic parasympathetic neurons (parasymNs) control unconscious body responses, including "rest-and-digest." ParasymN innervation is important for organ development,...
Autonomic parasympathetic neurons (parasymNs) control unconscious body responses, including "rest-and-digest." ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of functional human parasymNs from Schwann cell progenitors. We employ these neurons (1) to assess human autonomic nervous system (ANS) development, (2) to model neuropathy in the genetic disorder familial dysautonomia (FD), (3) to show parasymN dysfunction during SARS-CoV-2 infection, (4) to model the autoimmune disease Sjögren's syndrome (SS), and (5) to show that parasymNs innervate white adipocytes (WATs) during development and promote WAT maturation. Our model system could become instrumental for future disease modeling and drug discovery studies, as well as for human developmental studies.
Topics: Humans; Pluripotent Stem Cells; Cell Differentiation; Dysautonomia, Familial; Neurons; Sjogren's Syndrome; COVID-19; Animals; Parasympathetic Nervous System; Schwann Cells; Mice; SARS-CoV-2
PubMed: 38608707
DOI: 10.1016/j.stem.2024.03.011 -
Diabetes, Obesity & Metabolism Jul 2024To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN).
AIM
To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN).
MATERIALS AND METHODS
We used motif and discord extraction techniques, alongside long short-term memory networks, to analyse 12-lead, 10-s ECG tracings to detect CAN in patients with diabetes. The performance of these methods with the support vector machine classification model was evaluated using 10-fold cross validation with the following metrics: accuracy, precision, recall, F1 score, and area under the receiver-operating characteristic curve (AUC).
RESULTS
Among 205 patients (mean age 54 ± 17 years, 54% female), 100 were diagnosed with CAN, including 38 with definite or severe CAN (dsCAN) and 62 with early CAN (eCAN). The best model performance for dsCAN classification was achieved using both motifs and discords, with an accuracy of 0.92, an F1 score of 0.92, a recall at 0.94, a precision of 0.91, and an excellent AUC of 0.93 (95% confidence interval [CI] 0.91-0.94). For the detection of any stage of CAN, the approach combining motifs and discords yielded the best results, with an accuracy of 0.65, F1 score of 0.68, a recall of 0.75, a precision of 0.68, and an AUC of 0.68 (95% CI 0.54-0.81).
CONCLUSION
Our study highlights the potential of using ML techniques, particularly motifs and discords, to effectively detect dsCAN in patients with diabetes. This approach could be applied in large-scale screening of CAN, particularly to identify definite/severe CAN where cardiovascular risk factor modification may be initiated.
Topics: Humans; Female; Middle Aged; Male; Diabetic Neuropathies; Electrocardiography; Adult; Aged; Artificial Intelligence; Algorithms; Machine Learning; Support Vector Machine; Autonomic Nervous System Diseases; Diabetic Cardiomyopathies
PubMed: 38603589
DOI: 10.1111/dom.15578 -
Journal of Neural Transmission (Vienna,... Apr 2024Parkinson's disease (PD) has been linked to a vast array of vitamins among which vitamin B12 (Vit B12) is the most relevant and often investigated specially in the... (Review)
Review
Parkinson's disease (PD) has been linked to a vast array of vitamins among which vitamin B12 (Vit B12) is the most relevant and often investigated specially in the context of intrajejunal levodopa infusion therapy. Vit B12 deficiency, itself, has been reported to cause acute parkinsonism. Nevertheless, concrete mechanisms through which B12 deficiency interacts with PD in terms of pathophysiology, clinical manifestation and progression remains unclear. Recent studies have suggested that Vit B12 deficiency along with the induced hyperhomocysteinemia are correlated with specific PD phenotypes characterized with early postural instability and falls and more rapid motor progression, cognitive impairment, visual hallucinations and autonomic dysfunction. Specific clinical features such as polyneuropathy have also been linked to Vit B12 deficiency specifically in context of intrajejunal levodopa therapy. In this review, we explore the link between Vit B12 and PD in terms of physiopathology regarding dysfunctional neural pathways, neuropathological processes as well as reviewing the major clinical traits of Vit B12 deficiency in PD and Levodopa-mediated neuropathy. Finally, we provide an overview of the therapeutic effect of Vit B12 supplementation in PD and posit a practical guideline for Vit B12 testing and supplementation.
PubMed: 38602571
DOI: 10.1007/s00702-024-02769-z -
Cureus Mar 2024Multiple sclerosis (MS) is an autoimmune demyelinating neurological disorder primarily manifesting with a range of neurological symptoms, with cardiovascular autonomic...
Multiple sclerosis (MS) is an autoimmune demyelinating neurological disorder primarily manifesting with a range of neurological symptoms, with cardiovascular autonomic involvement being a rare occurrence. We report a case where a patient initially presented with Bell's palsy, without other notable symptoms or signs, and subsequently developed atrial fibrillation, hypertension, and hemiparesis. Magnetic resonance imaging (MRI) revealed extensive demyelination in the cerebral hemispheres, brainstem, and notably, the area postrema. The anatomy of the area postrema and its connections, in relation to neurogenic hypertension, are discussed. The demyelination in the area postrema was thought to be the cause of our patient's arrhythmias and acute hypertension. Furthermore, we discuss the cerebral origins of cardiac arrhythmias, with a focus on MS and other neurological conditions. This case underscores the rarity of isolated cranial neuropathies, such as Bell's palsy, as an initial sign of MS, marking the onset of a relapse.
PubMed: 38595879
DOI: 10.7759/cureus.55860 -
World Journal of Diabetes Mar 2024While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus (DM) is a well-known precursor to complications such as diabetic retinopathy, neuropathy...
While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus (DM) is a well-known precursor to complications such as diabetic retinopathy, neuropathy (including autonomic neuropathy), and nephropathy, a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin. Although, acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications, rarely other problems such as albuminuria, diabetic kidney disease, Charcot's neuroarthropathy, gastroparesis, and urinary bladder dysfunction are also encountered. The recently published a rare case of all these complications, occurring in a young type 1 diabetic female intensely managed during pregnancy, as a case report by Huret . It is essential to have a comprehensive understanding of the pathobiology, prevalence, predisposing factors, and management strategies for acute onset, or worsening of microvascular complications when rapid glycemic control is achieved, which serves to alleviate patient morbidity, enhance disease management compliance, and possibly to avoid medico-legal issues around this rare clinical problem. This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.
PubMed: 38591086
DOI: 10.4239/wjd.v15.i3.311 -
Journal of Clinical Ultrasound : JCU Jun 2024Similarly to the ventricles, the atria are under sympathetic/parasympathetic neural regulation. Accordingly, correlations were investigated between Ewing's standard...
Autonomic function and specific right atrial functions - Is there a relationship? Correlations from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.
INTRODUCTION
Similarly to the ventricles, the atria are under sympathetic/parasympathetic neural regulation. Accordingly, correlations were investigated between Ewing's standard cardiovascular reflex tests (SCRTs) and three-dimensional speckle-tracking echocardiography (3DSTE)-derived right atrial (RA) volumes and strains in healthy subjects.
MATERIALS AND METHODS
The study comprised 45 healthy adults, but 5 subjects were excluded due to inferior image quality for 3DSTE-derived RA assessments. The remaining 40 individuals being in sinus rhythm had a mean age of 35.1 ± 3.5 years (20 men). Two-dimensional, Doppler, 3DSTE and SCRTs were performed in all cases.
RESULTS
RA maximum volume and total and passive RA stroke volumes correlated with the Valsalva ratio. Active RA stroke volume and emptying fraction showed correlations with 30/15 ratio. Peak global and mean segmental RA circumferential (CS) and longitudinal strains (LS) showed correlation with the Valsalva ratio. At atrial contraction, global RA-LS and mean segmental RA-CS showed correlations with the Valsalva ratio. Moreover, mean segmental RA-CS correlated with 30/15 ratio and mean segmental RA radial strain showed correlations with systolic blood pressure in response to standing. Autonomic neuropathy score correlated with peak global RA-LS.
CONCLUSIONS
Autonomic function parameters have significant associations with specific RA functions in healthy adults, making the latter possible indicators of autonomic dysregulation.
Topics: Humans; Echocardiography, Three-Dimensional; Male; Female; Adult; Heart Atria; Atrial Function, Right; Autonomic Nervous System; Reference Values; Healthy Volunteers
PubMed: 38581157
DOI: 10.1002/jcu.23672 -
Molecular Genetics & Genomic Medicine Apr 2024Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene,... (Review)
Review
BACKGROUND
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self-mutilating behavior, and intellectual disability.
METHODS
Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing.
RESULTS
CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1 year (age range: 0.3-8 years). Two patients exhibited self-mutilation tendencies, intellectual disability, and developmental delay. Four NTRK1 (NM_002529.3) mutations, c.851-33T>A (p.?), c.2020G>T (p.Asp674Tyr), c.2303C>T (p.Pro768Leu), and c.574-156_850+1113del (exons 5-7 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851-33T>A (p.?) mutations and compound heterozygous for c.851-33T>A (p.?) and c.2020G>T (p.Asp674Tyr) mutation of NTRK1. The third patient with compound heterozygous mutations of c.2303C>T (p.Pro768Leu) and c.574-156_850+1113del (exons 5-7 del) displayed a late onset and milder clinical manifestation.
CONCLUSION
All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity.
Topics: Child; Child, Preschool; Female; Humans; Infant; Male; Channelopathies; Hereditary Sensory and Autonomic Neuropathies; Hypohidrosis; Indoles; Intellectual Disability; Pain; Pain Insensitivity, Congenital; Propionates
PubMed: 38581121
DOI: 10.1002/mgg3.2430 -
Diabetes & Metabolic Syndrome Mar 2024Diabetic gastroparesis (DGp) is a common and preventable complication of uncontrolled diabetes mellitus (D.M.) and significantly affects the Quality of Life of patients.... (Review)
Review
BACKGROUND AND AIMS
Diabetic gastroparesis (DGp) is a common and preventable complication of uncontrolled diabetes mellitus (D.M.) and significantly affects the Quality of Life of patients. Diagnosis and management present as a clinical challenge due to the disease's complexity and limited effective therapeutic options. This review aims to comprehensively outline the pathogenesis, diagnosis, and management of diabetic gastroparesis, evaluating evolving approaches to guide clinicians and provide future recommendations.
METHODS
A literature review was conducted on scholarly databases of PubMed, Google Scholar, Scopus and Web of Science encompassing published articles, gray literature and relevant clinical guidelines. Data were synthesized and analyzed to provide a comprehensive overview of diabetic gastroparesis, focusing on pathogenesis, diagnosis, and management.
RESULTS
The review intricately explores the pathogenesis contributing to diabetic gastroparesis, emphasizing autonomic neuropathy, oxidative stress, inflammation, hormonal dysregulation, microbiota alterations, and gastrointestinal neuropathy. Primary management strategies are underscored, including lifestyle modifications, symptom relief, and glycemic control. The discussion encompasses pharmacological and surgical options, highlighting the importance of a multidisciplinary approach involving various healthcare professionals for comprehensive patient care.
CONCLUSION
This review offers a thorough understanding of pathogenesis, diagnosis, and management of diabetic gastroparesis, underlining evolving approaches for clinicians. A multidisciplinary approach is crucial to address both the physical and mental health aspects of diabetes and its complications.
Topics: Humans; Gastroparesis; Diabetes Complications; Disease Management; Quality of Life; Prognosis
PubMed: 38579489
DOI: 10.1016/j.dsx.2024.102994 -
BMC Pediatrics Apr 2024Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes, impacting the autonomic nerves that regulate the heart and blood vessels. Timely...
BACKGROUND
Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes, impacting the autonomic nerves that regulate the heart and blood vessels. Timely recognition and treatment of CAN are crucial in averting the onset of cardiovascular complications. Both clinically apparent autonomic neuropathy and subclinical autonomic neuropathy, particularly CAN pose a significant risk of morbidity and mortality in children with type 1 diabetes mellitus (T1DM). Notably, CAN can progress silently before manifesting clinically. In our study, we assessed patients with poor metabolic control, without symptoms, following the ISPAD 2022 guideline. The objective is is to determine which parameters we can use to diagnose CAN in the subclinical period.
METHODS
Our study is a cross-sectional case-control study that includes 30 children diagnosed with T1DM exhibiting poor metabolic control (average HbA1c > 8.5% for at least 1 year) according to the ISPAD 2022 Consensus Guide. These patients, who are under the care of the pediatric diabetes clinic, underwent evaluation through four noninvasive autonomic tests: echocardiography, 24-h Holter ECG for heart rate variability (HRV), cardiopulmonary exercise test, and tilt table test.
RESULTS
The average age of the patients was 13.73 ± 1.96 years, the average diabetes duration was 8 ± 3.66 years, and the 1-year average HbA1c value was 11.34 ± 21%. In our asymptomatic and poorly metabolically controlled patient group, we found a decrease in HRV values, the presence of postural hypotension with the tilt table test, and a decrease in ventricular diastolic functions that are consistent with the presence of CAN. Despite CAN, the systolic functions of the ventricles were preserved, and the dimensions of the cardiac chambers and cardiopulmonary exercise test were normal.
CONCLUSIONS
CAN is a common complication of T1DM, often associated with the patient's age and poor glycemic control. HRV, active orthostatic tests, and the evaluation of diastolic dysfunctions play significant roles in the comprehensive assessment of CAN. These diagnostic measures are valuable tools in identifying autonomic dysfunction at an early stage, allowing for timely intervention and management to mitigate the impact of cardiovascular complications associated with T1DM.
Topics: Humans; Child; Adolescent; Diabetes Mellitus, Type 1; Cross-Sectional Studies; Case-Control Studies; Glycated Hemoglobin; Diabetic Neuropathies; Autonomic Nervous System Diseases; Heart Rate
PubMed: 38561716
DOI: 10.1186/s12887-024-04644-y -
Cureus Feb 2024SARS-CoV-2 vaccinations can lead to complications, including post-acute COVID-19 vaccination syndrome (PACVS). There has been no report of a patient with PACVS...
SARS-CoV-2 vaccinations can lead to complications, including post-acute COVID-19 vaccination syndrome (PACVS). There has been no report of a patient with PACVS presenting with Guillain-Barre syndrome (GBS), myocarditis/pericarditis, immunodeficiency, or coagulopathy after the second BNT162b2 dose. The patient is a 51-year-old woman with chronic myopericarditis, coagulopathy due to factor-VIII increase and protein-S deficiency, GBS, and a number of other ocular, dermatological, immunological, and central nervous system abnormalities related to the second dose of the BNT172b2 vaccine. GBS manifested with mild, multiple cranial nerve lesions, small fibre neuropathy (SFN) affecting the autonomic system with postural tachycardia syndrome (POTS) and orthostatic hypotension, and sensory disturbances in the upper and lower limbs. PACVS was diagnosed months after onset, but despite the delayed diagnosis, the patient benefited from glucocorticoids, repeated HELP apheresis, and multiple symptomatic treatments. The case shows that SARS-CoV-2 vaccination can be complicated by PACVS manifesting as chronic myopericarditis, coagulopathy, GBS with predominant dysautonomia, and impaired immune competence, and that diagnosis of PACVS can be delayed for months. Delayed diagnosis of PACVS may result in a delay in appropriate treatment and the prolongation of disabling symptoms. Patients and physicians should be made aware of PACVS to improve diagnostic and therapeutic management in terms of patient and healthcare system costs.
PubMed: 38558730
DOI: 10.7759/cureus.55205