Materiały źródłowe

• #1 Autonomic Neuropathy: Background, Pathophysiology, Inherited Autonomic Neuropathies

  https://emedicine.medscape.com/article/1173756-overview

  The pathophysiology of autonomic neuropathies is variable and depends upon the underlying medical conditions. We have chosen to classify the autonomic neuropathies into hereditary and acquired. The acquired autonomic neuropathies may then be subsequently subdivided into primary or secondary. […] The acquired autonomic neuropathies are much more prevalent than the inherited ones. Here, we subclassify the acquired autonomic neuropathies into primary and secondary disorders. Primary autonomic neuropathies are disorders that are idiopathic or that have autonomic neuropathy as a characteristic feature of the disease process itself. In the secondary autonomic neuropathies, an identifiable cause, such as a nutritional deficiency, may lead to autonomic neuropathy, but does not have autonomic neuropathy as a defining feature of the disease process. Subclassification can be somewhat artificial as the true mechanism of action is not clear in all cases, although it can be helpful when trying to develop an understanding of autonomic neuropathy.

• #2 Autonomic neuropathy – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/autonomic-neuropathy/symptoms-causes/syc-20369829

  Autonomic neuropathy occurs when there is damage to the nerves that control automatic body functions. It can affect blood pressure, temperature control, digestion, bladder function and even sexual function. […] The nerve damage affects the messages sent between the brain and other organs and areas of the autonomic nervous system. These areas include the heart, blood vessels and sweat glands. […] Diabetes is the most common cause of autonomic neuropathy. It can also be caused by other health conditions, viral or bacterial infections, or some medications. Symptoms and treatment vary based on which nerves are damaged. […] Many health conditions can cause autonomic neuropathy. It can also be a side effect of treatments for other diseases, such as cancer. Some common causes of autonomic neuropathy include:

• #3 Autonomic neuropathy – Wikipedia

  https://en.wikipedia.org/wiki/Autonomic_neuropathy

  Autonomic neuropathy (AN or AAN) is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system), affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. […] Autonomic neuropathy is one cause of malfunction of the autonomic nervous system (referred to as dysautonomia), but not the only one; some conditions affecting the brain or spinal cord also may cause autonomic dysfunction, such as multiple system atrophy, and therefore, may cause similar symptoms to autonomic neuropathy. […] Many health conditions can cause autonomic neuropathy. Some common causes of autonomic neuropathy include: […] Diabetes, which is the most common cause of autonomic neuropathy, can gradually cause nerve damage throughout the body.

• #4 Autonomic Neuropathy: Background, Pathophysiology, Inherited Autonomic Neuropathies

  https://emedicine.medscape.com/article/1173756-overview

  The pathophysiology of autonomic neuropathies is variable and depends upon the underlying medical conditions. We have chosen to classify the autonomic neuropathies into hereditary and acquired. The acquired autonomic neuropathies may then be subsequently subdivided into primary or secondary. […] The acquired autonomic neuropathies are much more prevalent than the inherited ones. Here, we subclassify the acquired autonomic neuropathies into primary and secondary disorders. Primary autonomic neuropathies are disorders that are idiopathic or that have autonomic neuropathy as a characteristic feature of the disease process itself. In the secondary autonomic neuropathies, an identifiable cause, such as a nutritional deficiency, may lead to autonomic neuropathy, but does not have autonomic neuropathy as a defining feature of the disease process. Subclassification can be somewhat artificial as the true mechanism of action is not clear in all cases, although it can be helpful when trying to develop an understanding of autonomic neuropathy.

• #5 Autonomic neuropathy – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/autonomic-neuropathy/symptoms-causes/syc-20369829

  Autonomic neuropathy occurs when there is damage to the nerves that control automatic body functions. It can affect blood pressure, temperature control, digestion, bladder function and even sexual function. […] The nerve damage affects the messages sent between the brain and other organs and areas of the autonomic nervous system. These areas include the heart, blood vessels and sweat glands. […] Diabetes is the most common cause of autonomic neuropathy. It can also be caused by other health conditions, viral or bacterial infections, or some medications. Symptoms and treatment vary based on which nerves are damaged. […] Many health conditions can cause autonomic neuropathy. It can also be a side effect of treatments for other diseases, such as cancer. Some common causes of autonomic neuropathy include:

• #6 Autonomic neuropathy – Wikipedia

  https://en.wikipedia.org/wiki/Autonomic_neuropathy

  Autonomic neuropathy (AN or AAN) is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system), affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. […] Autonomic neuropathy is one cause of malfunction of the autonomic nervous system (referred to as dysautonomia), but not the only one; some conditions affecting the brain or spinal cord also may cause autonomic dysfunction, such as multiple system atrophy, and therefore, may cause similar symptoms to autonomic neuropathy. […] Many health conditions can cause autonomic neuropathy. Some common causes of autonomic neuropathy include: […] Diabetes, which is the most common cause of autonomic neuropathy, can gradually cause nerve damage throughout the body.

• #7 Autonomic neuropathy – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/autonomic-neuropathy/symptoms-causes/syc-20369829

  Diabetes, especially when poorly controlled, is the most common cause of autonomic neuropathy. Diabetes can gradually cause nerve damage throughout the body. […] Autoimmune diseases, in which your immune system attacks and damages parts of your body, including your nerves. Examples include Sjogren syndrome, systemic lupus erythematosus, rheumatoid arthritis and celiac disease. Guillain-Barre syndrome is an autoimmune disease that happens rapidly and can affect autonomic nerves. […] Autonomic neuropathy may also be caused by an immune system attack triggered by some cancers (paraneoplastic syndrome). […] Certain inherited disorders also can cause autonomic neuropathy.

• #8 Autonomic neuropathy – Wikipedia

  https://en.wikipedia.org/wiki/Autonomic_neuropathy

  Autoimmune diseases, in which the immune system attacks and damages parts of the body, including the nerves. Examples include Sjgren syndrome, systemic lupus erythematosus, rheumatoid arthritis and celiac disease. GuillainBarr syndrome is an autoimmune disease that happens rapidly and can affect autonomic nerves.

• #9 Autonomic peripheral neuropathy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/15811460/

  The autonomic neuropathies are a group of disorders in which the small, lightly myelinated and unmyelinated autonomic nerve fibres are selectively targeted. […] Diabetes is the most common cause of autonomic neuropathy in more developed countries. […] Autonomic neuropathies can also occur as a result of amyloid deposition, after acute infection, as part of a paraneoplastic syndrome, and after exposure to neurotoxins including therapeutic drugs. […] Certain antibodies (eg, anti-Hu and those directed against neuronal nicotinic acetylcholine receptor) are associated with autonomic signs and symptoms. […] There are several familial autonomic neuropathies with autosomal dominant, autosomal recessive, or X-linked patterns of inheritance. […] Autonomic dysfunction can occur in association with specific infections. […] The availability of sensitive and reproducible measures of autonomic function has improved physicians’ ability to diagnose these disorders.

• #10 Cardiac Autonomic Neuropathy in Diabetes Mellitus: Pathogenesis, Epidemiology, Diagnosis and Clinical Implications: A Narrative Review

  https://www.mdpi.com/2077-0383/14/3/671

  Cardiac autonomic neuropathy (CAN) is arguably among the most frequently disregarded of all the major consequences of diabetes and leads to the cardiovascular autonomic nerve system dysfunction (EDIC). The impairment of cardiovascular autonomic function in individuals with confirmed DM after alternative reasons have been ruled out is known as CAN, according to the Toronto Consensus Panel on Diabetic Neuropathy Subcommittee. About 7% of people with T1D or T2D had CAN identified at diagnosis. For people with DM type 1 and type 2, the risk is thought to rise by roughly 6% and 2% every year, respectively. The prevalence of CAN rises significantly with the length of diabetes, even if it is relatively low in newly diagnosed individuals with T1D. In the DCCT/EDIC cohort, incidence rates of at least 30% were noted over twenty years of diabetes duration. In patients who are diagnosed with T2D, the incidence of CAN also rises with the length of disease and may reach 60% of patients after 15 years. There is disagreement on how gender affects CAN. There were no variations in the frequency of CAN between men (35%) and women (37%), according to the EURODIAB IDDM Complications Study, but according to the ACCORD study, women (4.7%) were more likely than males (2.6%) to have CAN. Autonomic neuropathy was significantly correlated with the duration of diabetes, age, glycated hemoglobin, retinopathy, microalbuminuria, hypoglycemia, ketoacidosis, smoking, low HDL cholesterol, total cholesterol/HDL cholesterol ratio, fasting triglycerides, and diastolic blood pressure. According to the EURODIAB IDDM Complications Study, autonomic neuropathy was linked to a higher risk of cardiovascular disease. Based on the results of multiple epidemiological studies conducted among people with diabetes, those with CAN have a five-fold greater 5-year mortality rate from this significant consequence than people without cardiovascular autonomic dysfunction. Numerous processes and pathways contribute to CAN, which is brought on by intricate interconnections and ultimately results in neuronal ischemia and death. Hyperglycemia is the primary cause of the pathogenic process. Oxidative stress brought on by hyperglycemia and harmful advanced glycosylation products alter endothelium, membrane permeability, and mitochondrial functioning. Several cellular processes, communication between cells and the surrounding matrix, transcription factors, and gene expression are all disrupted by these various routes. All of this results in neuronal death and malfunction. A variety of clinical presentations, including subtle appearances of symptoms at different stages of its natural history, are what define CAN. Nerve length has an inverse association with the progression of nervous system injury, with the vagus nerve being impacted first. Sympathetic predominance results from parasympathetic system failure in early illness. Clinically, this manifests as tachycardia at rest. A failure to react appropriately to physiological stresses, such as exercise, is a result of advanced CAN, which causes a constant heart rate. Exercise intolerance is the clinical manifestation of this reduced response.

• #11 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications

  https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm

  Cardiovascular autonomic neuropathy (CAN) is a microvascular complication defined as the impairment of cardiovascular autonomic control in persons with diabetes, with no other causes. The etiology of CAN is multifactorial, and several conditions are associated with CAN, such as hyperglycemia, insulin resistance, prediabetes, obesity, hypertension, dyslipidemia, metabolic syndrome, and obstructive sleep apnea (OSA). However, it is mainly recognized as a major complication of type 1 and type 2 diabetes mellitus, since diabetic neuropathies are the most prevalent chronic microvascular complications of diabetes. […] The pathophysiological mechanism responsible for this lesion is multifactorial. Although the mechanisms associated with CAN development remain uncertain in their entirety, the main mechanism is hyperglycemia. Hyperglycemia directly favors an increase in the production of reactive oxygen species (ROS) and advanced glycation end products (AGEs), which are a heterogeneous group of compounds.

• #12 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications

  https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm

  Cardiovascular autonomic neuropathy (CAN) is a microvascular complication defined as the impairment of cardiovascular autonomic control in persons with diabetes, with no other causes. The etiology of CAN is multifactorial, and several conditions are associated with CAN, such as hyperglycemia, insulin resistance, prediabetes, obesity, hypertension, dyslipidemia, metabolic syndrome, and obstructive sleep apnea (OSA). However, it is mainly recognized as a major complication of type 1 and type 2 diabetes mellitus, since diabetic neuropathies are the most prevalent chronic microvascular complications of diabetes. […] The pathophysiological mechanism responsible for this lesion is multifactorial. Although the mechanisms associated with CAN development remain uncertain in their entirety, the main mechanism is hyperglycemia. Hyperglycemia directly favors an increase in the production of reactive oxygen species (ROS) and advanced glycation end products (AGEs), which are a heterogeneous group of compounds.

• #13

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. […] Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. […] The precise pathophysiology of CAN remains unclear; however, multiple pathways leading to microvascular complications have been identified: AGE-mediated inflammation, increased oxidative stress and reactive oxygen species causing direct nerve cell damage, activation of the hexosamine, protein kinase C and polyol pathways and subsequent osmotic and oxidative stress, and neuronal ischaemia due to diabetic microangiopathy. […] More recently, mitochondrial dysfunction, lipid metabolites in early-onset type 2 diabetes and collagen turnover in type 1 diabetes have been investigated and are emerging pathophysiological pathways in diabetic autonomic neuropathy.

• #14

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. […] Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. […] The precise pathophysiology of CAN remains unclear; however, multiple pathways leading to microvascular complications have been identified: AGE-mediated inflammation, increased oxidative stress and reactive oxygen species causing direct nerve cell damage, activation of the hexosamine, protein kinase C and polyol pathways and subsequent osmotic and oxidative stress, and neuronal ischaemia due to diabetic microangiopathy. […] More recently, mitochondrial dysfunction, lipid metabolites in early-onset type 2 diabetes and collagen turnover in type 1 diabetes have been investigated and are emerging pathophysiological pathways in diabetic autonomic neuropathy.

• #15

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. […] Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. […] The precise pathophysiology of CAN remains unclear; however, multiple pathways leading to microvascular complications have been identified: AGE-mediated inflammation, increased oxidative stress and reactive oxygen species causing direct nerve cell damage, activation of the hexosamine, protein kinase C and polyol pathways and subsequent osmotic and oxidative stress, and neuronal ischaemia due to diabetic microangiopathy. […] More recently, mitochondrial dysfunction, lipid metabolites in early-onset type 2 diabetes and collagen turnover in type 1 diabetes have been investigated and are emerging pathophysiological pathways in diabetic autonomic neuropathy.

• #16

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. […] Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. […] The precise pathophysiology of CAN remains unclear; however, multiple pathways leading to microvascular complications have been identified: AGE-mediated inflammation, increased oxidative stress and reactive oxygen species causing direct nerve cell damage, activation of the hexosamine, protein kinase C and polyol pathways and subsequent osmotic and oxidative stress, and neuronal ischaemia due to diabetic microangiopathy. […] More recently, mitochondrial dysfunction, lipid metabolites in early-onset type 2 diabetes and collagen turnover in type 1 diabetes have been investigated and are emerging pathophysiological pathways in diabetic autonomic neuropathy.

• #17

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Genetic susceptibility may play a role in the development of diabetic neuropathy, with several genes identified as being involved in endothelial dysfunction, oxidative nitrosative stress and lipid metabolism. […] Further work is essential to identify the molecular and cellular mechanisms involved in the pathogenesis of CAN in terms of both development and progression, with a greater understanding needed of mitochondrial dysfunction and genetics/genomics.

• #18

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. […] Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. […] The precise pathophysiology of CAN remains unclear; however, multiple pathways leading to microvascular complications have been identified: AGE-mediated inflammation, increased oxidative stress and reactive oxygen species causing direct nerve cell damage, activation of the hexosamine, protein kinase C and polyol pathways and subsequent osmotic and oxidative stress, and neuronal ischaemia due to diabetic microangiopathy. […] More recently, mitochondrial dysfunction, lipid metabolites in early-onset type 2 diabetes and collagen turnover in type 1 diabetes have been investigated and are emerging pathophysiological pathways in diabetic autonomic neuropathy.

• #19

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Genetic susceptibility may play a role in the development of diabetic neuropathy, with several genes identified as being involved in endothelial dysfunction, oxidative nitrosative stress and lipid metabolism. […] Further work is essential to identify the molecular and cellular mechanisms involved in the pathogenesis of CAN in terms of both development and progression, with a greater understanding needed of mitochondrial dysfunction and genetics/genomics.

• #20 Cardiac autonomic neuropathy in patients with diabetes mellitus: curre | DMSO

  https://www.dovepress.com/cardiac-autonomic-neuropathy-in-patients-with-diabetes-mellitus-curren-peer-reviewed-fulltext-article-DMSO

  CAN might occur as a result of autoimmune autonomic ganglionopathy. This is where autonomic failure occurs in the presence of antibodies to the nicotinic acetylcholine receptor of autonomic ganglia, leading to severe autonomic manifestations. […] Several genes have been linked to the development and progression of diabetic polyneuropathy and CAN, among which are TCF7L2, APOE, and ACE. […] Inflammation plays an important role in the pathogenesis of diabetes and its related micro- and macrovascular complications. CAN has been associated with increased inflammatory markers such as CRP, IL6, and TNF, and adipose-tissue inflammation.

• #21 Cardiac Autonomic Neuropathy in Diabetes Mellitus: Pathogenesis, Epidemiology, Diagnosis and Clinical Implications: A Narrative Review

  https://www.mdpi.com/2077-0383/14/3/671

  Cardiac autonomic neuropathy (CAN) is arguably among the most frequently disregarded of all the major consequences of diabetes and leads to the cardiovascular autonomic nerve system dysfunction (EDIC). The impairment of cardiovascular autonomic function in individuals with confirmed DM after alternative reasons have been ruled out is known as CAN, according to the Toronto Consensus Panel on Diabetic Neuropathy Subcommittee. About 7% of people with T1D or T2D had CAN identified at diagnosis. For people with DM type 1 and type 2, the risk is thought to rise by roughly 6% and 2% every year, respectively. The prevalence of CAN rises significantly with the length of diabetes, even if it is relatively low in newly diagnosed individuals with T1D. In the DCCT/EDIC cohort, incidence rates of at least 30% were noted over twenty years of diabetes duration. In patients who are diagnosed with T2D, the incidence of CAN also rises with the length of disease and may reach 60% of patients after 15 years. There is disagreement on how gender affects CAN. There were no variations in the frequency of CAN between men (35%) and women (37%), according to the EURODIAB IDDM Complications Study, but according to the ACCORD study, women (4.7%) were more likely than males (2.6%) to have CAN. Autonomic neuropathy was significantly correlated with the duration of diabetes, age, glycated hemoglobin, retinopathy, microalbuminuria, hypoglycemia, ketoacidosis, smoking, low HDL cholesterol, total cholesterol/HDL cholesterol ratio, fasting triglycerides, and diastolic blood pressure. According to the EURODIAB IDDM Complications Study, autonomic neuropathy was linked to a higher risk of cardiovascular disease. Based on the results of multiple epidemiological studies conducted among people with diabetes, those with CAN have a five-fold greater 5-year mortality rate from this significant consequence than people without cardiovascular autonomic dysfunction. Numerous processes and pathways contribute to CAN, which is brought on by intricate interconnections and ultimately results in neuronal ischemia and death. Hyperglycemia is the primary cause of the pathogenic process. Oxidative stress brought on by hyperglycemia and harmful advanced glycosylation products alter endothelium, membrane permeability, and mitochondrial functioning. Several cellular processes, communication between cells and the surrounding matrix, transcription factors, and gene expression are all disrupted by these various routes. All of this results in neuronal death and malfunction. A variety of clinical presentations, including subtle appearances of symptoms at different stages of its natural history, are what define CAN. Nerve length has an inverse association with the progression of nervous system injury, with the vagus nerve being impacted first. Sympathetic predominance results from parasympathetic system failure in early illness. Clinically, this manifests as tachycardia at rest. A failure to react appropriately to physiological stresses, such as exercise, is a result of advanced CAN, which causes a constant heart rate. Exercise intolerance is the clinical manifestation of this reduced response.

• #22 Correlation of staging and risk factors with cardiovascular autonomic neuropathy in patients with type II diabetes mellitus | Scientific Reports

  https://www.nature.com/articles/s41598-021-80962-w

  These different pathways induce changes in gene expression, transcription factors, interruption of several cell functions, and communication between the cells and the surrounding matrix. […] Like somatic neuropathies, some investigators have shown that autonomic nerves may be affected in a length-dependent manner. […] This study found a significant correlation between CAN and glycemic control, duration of diabetes, and WHR, but not BMI. […] These findings underscore the role of insulin resistance not only in the etiology of metabolic syndrome but also as a determinant of cardiac autonomic dysfunction. […] The criterion for CAN severity was an increase of at least one point in the Spallone score. […] The E/I ratio, the 30:15 ratio, and the sustained handgrip were significantly reduced while the BP response to standing was increased.

• #23 Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis

  https://www.mdpi.com/1422-0067/25/4/2296

  Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. […] AAG was discovered by Vernino and colleagues in 2000 to be caused by autoantibodies to the ganglionic nicotinic acetylcholine receptor (gAChR), prior to which the disorder was called acute pandysautonomia. […] The key to the differential diagnosis of peripheral neuropathies presenting with autonomic dysfunction is the combination of detailed history taking, a thorough assessment of the findings of the neurological examination, and comprehensive laboratory examinations. […] Whether Abs against nAChRα3 are actually pathogenic in human AAG is an important issue. […] The EPSP amplitude recovered by day 7, despite the persistence of gAChR antibodies in the mouse serum.

• #24 Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis

  https://www.mdpi.com/1422-0067/25/4/2296

  The conceivable mechanism is that the nAChR Abs affect synaptic transmission in autonomic ganglia in the following three-step process: (1) Abs binding to the nAChR; (2) accelerated internalization and degradation of AChR molecules crosslinked by Abs, which leads to reduced numbers of nAChR; and (3) Abs binding to the nAChR cause a functional block of the nAChR. […] The agonistic effects of gAChR autoantibodies need further physiological investigation in the future. […] The pathogenic mechanisms underlying this variability are not yet clear. […] The presence of autoantibodies to autonomic nervous system-related receptors, especially GPCRs, in long COVID has attracted attention.

• #25 Autonomic Neuropathy: Background, Pathophysiology, Inherited Autonomic Neuropathies

  https://emedicine.medscape.com/article/1173756-overview

  Autonomic neuropathy may occur in approximately 50% of adults with celiac disease, leading to clinical features of presyncope and postural nausea. Autonomic denervation may be related to antineuronal antibodies; the neuropathy does not appear to respond to a gluten-free diet. […] Autoantibodies can be found against gangliosides, such as with anti-GM1 antibodies. Pathologic studies of the autonomic nervous system in GBS may demonstrate edema and inflammation of autonomic ganglia and destruction of peripheral ganglion cells. Chromatolysis, mononuclear cell infiltration, and nodules of Nageotte can be found within sympathetic ganglia.

• #26 Autonomic Neuropathy: Background, Pathophysiology, Inherited Autonomic Neuropathies

  https://emedicine.medscape.com/article/1173756-overview

  Autonomic neuropathy may occur in approximately 50% of adults with celiac disease, leading to clinical features of presyncope and postural nausea. Autonomic denervation may be related to antineuronal antibodies; the neuropathy does not appear to respond to a gluten-free diet. […] Autoantibodies can be found against gangliosides, such as with anti-GM1 antibodies. Pathologic studies of the autonomic nervous system in GBS may demonstrate edema and inflammation of autonomic ganglia and destruction of peripheral ganglion cells. Chromatolysis, mononuclear cell infiltration, and nodules of Nageotte can be found within sympathetic ganglia.

• #27 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J

  https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251

  Diabetes triggers multiple reactions that promote neuropathic changes, such as advanced glycosylation end products from glycation of proteins, activation of poly(ADP ribose) polymerase reductase pathways, direct DNA damage, negative effects on neuronal regeneration and repair, reduced neurotransmitter release and synapse function, altered Na/K/ATPase pump, and damage to endoplasmic reticulum that activates apoptotic pathways. […] Microvascular changes of diabetes, including retinopathy and albuminuria, are associated with progression of CAN based on the results from the EURODIAB study. Increased production of cytokines such as interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as well as inflammation in general, are known to be associated with CAN. […] Just like the somatic neuropathies, diabetes affects autonomic nerves in a length-dependent fashion. As a result, CAN often first manifests in the vagus nerve, the body’s longest parasympathetic autonomic nerve and the one responsible for almost three-quarters of parasympathetic activity; damage to the vagus nerve causes resting tachycardia and an overall decrease in parasympathetic tone. In the later stages of CAN, sympathetic denervation occurs, starting from the apex of the ventricles to the base of the heart.

• #28 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J

  https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251

  Diabetes triggers multiple reactions that promote neuropathic changes, such as advanced glycosylation end products from glycation of proteins, activation of poly(ADP ribose) polymerase reductase pathways, direct DNA damage, negative effects on neuronal regeneration and repair, reduced neurotransmitter release and synapse function, altered Na/K/ATPase pump, and damage to endoplasmic reticulum that activates apoptotic pathways. […] Microvascular changes of diabetes, including retinopathy and albuminuria, are associated with progression of CAN based on the results from the EURODIAB study. Increased production of cytokines such as interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as well as inflammation in general, are known to be associated with CAN. […] Just like the somatic neuropathies, diabetes affects autonomic nerves in a length-dependent fashion. As a result, CAN often first manifests in the vagus nerve, the body’s longest parasympathetic autonomic nerve and the one responsible for almost three-quarters of parasympathetic activity; damage to the vagus nerve causes resting tachycardia and an overall decrease in parasympathetic tone. In the later stages of CAN, sympathetic denervation occurs, starting from the apex of the ventricles to the base of the heart.

• #29 Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

  https://www.e-dmj.org/journal/view.php?number=372

  Diabetic autonomic neuropathy (DAN) is one of the major diabetic complications, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). […] The first reason is that DAN is a systemic disease that involves every organ in the body by affecting the entire autonomic nervous system (ANS) and it leads to increase in morbidity and mortality. […] DAN includes both parasympathetic and sympathetic nerve dysfunction in both T1DM and T2DM patients. […] The explanation for these discrepancies might be that parasympathetic nerve function is more severely affected in T2DM patients. […] As parasympathetic nerve damage seemed to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was like Ewing’s concept.

• #30 Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

  https://www.e-dmj.org/journal/view.php?doi=10.4093/dmj.2015.39.6.461

  This could be explained by basic morphological difference in autonomic nerves. […] Therefore, the order of morphological changes in sympathetic and parasympathetic nerves of various organs in diabetic patients must be evaluated. […] Autonomic dysfunction (e.g., heightened activity of the sympathetic nervous system and suppressed activity of the parasympathetic nervous system) impairs the ability of the ANS to regulate the cardiovascular system, and inflammatory, metabolic and neurological disease processes. […] Therefore, the role of autonomic imbalance and mechanisms in DAN require further exploration. […] The autonomic neuropathic stomach showed decreased mucosal nerve fiber length and volume density, and an altered mucosal nerve fiber innervation pattern in animal diabetes model and human diabetics.

• #31 Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

  https://www.e-dmj.org/journal/view.php?doi=10.4093/dmj.2015.39.6.461

  Although gastric mucosal nerve fiber loss is associated with diabetic sensory peripheral neuropathy and diabetes duration, intraepidermal nerve fiber density could not predict mucosal nerve fiber deficiency. […] Therefore, we need a precise evaluation method for sympathetic and parasympathetic nerve fiber innervation and degeneration. […] To diagnose specific autonomic neuropathy, we must perform specific tests. […] Recently, skin biopsy has been widely used as a diagnostic method for somatic and autonomic neuropathy. […] Additionally, immunohistochemistry with an optical clearing process can discriminate the sympathetic and parasympathetic nerve fibers. […] These advances enable the evaluation and monitoring of the autonomic nerve fibers, such as sympathetic and parasympathetic nerve fiber innervation, morphologic changes, and degeneration and regeneration sequences.

• #32 Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

  https://www.e-dmj.org/journal/view.php?number=372

  This method is an important diagnostic tool for small fiber sensory neuropathy and autonomic neuropathy according to qualitative and quantitative studies of sensory and autonomic nerve fiber densities and morphology in diabetic research. […] Morphometric analysis of skin nerves is readily accomplished through the use of immunohistochemical techniques, and has proved to be reliable, reproducible and unaffected by the severity of neuropathy. […] Therefore, we need a precise evaluation method for sympathetic and parasympathetic nerve fiber innervation and degeneration. […] In clinical practice, various autonomic function tests have been proposed to study patients with suspected autonomic neuropathy. […] To diagnose specific autonomic neuropathy, we must perform specific tests. […] Recently, skin biopsy has been widely used as a diagnostic method for somatic and autonomic neuropathy. […] Additionally, immunohistochemistry with an optical clearing process can discriminate the sympathetic and parasympathetic nerve fibers.

• #33 Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

  https://www.e-dmj.org/journal/view.php?doi=10.4093/dmj.2015.39.6.461

  Diabetic autonomic neuropathy (DAN) is one of the major diabetic complications, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). […] The first reason is that DAN is a systemic disease that involves every organ in the body by affecting the entire autonomic nervous system (ANS) and it leads to increase in morbidity and mortality. […] DAN includes both parasympathetic and sympathetic nerve dysfunction in both T1DM and T2DM patients. […] The explanation for these discrepancies might be that parasympathetic nerve function is more severely affected in T2DM patients. […] As parasympathetic nerve damage seemed to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was like Ewing’s concept.

• #34 Diabetic autonomic neuropathy – UpToDate

  https://www.uptodate.com/contents/diabetic-autonomic-neuropathy

  Diabetic autonomic neuropathy (DAN) is a common form of neuropathy in patients with diabetes mellitus characterized by dysfunction due to impairment of peripheral autonomic nerves. A wide spectrum of manifestations can affect many different organ systems, including the cardiovascular, gastrointestinal, genitourinary, sudomotor and vasomotor, and neuroendocrine systems (table 1). […] The prevalence of DAN increases with the duration of diabetes. It may be identified in patients at the time of diabetes diagnosis in up to 7 percent but can be as high as 50 percent after 15 years. […] Early recognition of clinical or subclinical DAN is useful for risk stratification and to guide specific glycemic, lipid, and blood pressure targets.

• #35 Cardiac Autonomic Neuropathy in Diabetes Mellitus: Pathogenesis, Epidemiology, Diagnosis and Clinical Implications: A Narrative Review

  https://www.mdpi.com/2077-0383/14/3/671

  Cardiac autonomic neuropathy (CAN) is arguably among the most frequently disregarded of all the major consequences of diabetes and leads to the cardiovascular autonomic nerve system dysfunction (EDIC). The impairment of cardiovascular autonomic function in individuals with confirmed DM after alternative reasons have been ruled out is known as CAN, according to the Toronto Consensus Panel on Diabetic Neuropathy Subcommittee. About 7% of people with T1D or T2D had CAN identified at diagnosis. For people with DM type 1 and type 2, the risk is thought to rise by roughly 6% and 2% every year, respectively. The prevalence of CAN rises significantly with the length of diabetes, even if it is relatively low in newly diagnosed individuals with T1D. In the DCCT/EDIC cohort, incidence rates of at least 30% were noted over twenty years of diabetes duration. In patients who are diagnosed with T2D, the incidence of CAN also rises with the length of disease and may reach 60% of patients after 15 years. There is disagreement on how gender affects CAN. There were no variations in the frequency of CAN between men (35%) and women (37%), according to the EURODIAB IDDM Complications Study, but according to the ACCORD study, women (4.7%) were more likely than males (2.6%) to have CAN. Autonomic neuropathy was significantly correlated with the duration of diabetes, age, glycated hemoglobin, retinopathy, microalbuminuria, hypoglycemia, ketoacidosis, smoking, low HDL cholesterol, total cholesterol/HDL cholesterol ratio, fasting triglycerides, and diastolic blood pressure. According to the EURODIAB IDDM Complications Study, autonomic neuropathy was linked to a higher risk of cardiovascular disease. Based on the results of multiple epidemiological studies conducted among people with diabetes, those with CAN have a five-fold greater 5-year mortality rate from this significant consequence than people without cardiovascular autonomic dysfunction. Numerous processes and pathways contribute to CAN, which is brought on by intricate interconnections and ultimately results in neuronal ischemia and death. Hyperglycemia is the primary cause of the pathogenic process. Oxidative stress brought on by hyperglycemia and harmful advanced glycosylation products alter endothelium, membrane permeability, and mitochondrial functioning. Several cellular processes, communication between cells and the surrounding matrix, transcription factors, and gene expression are all disrupted by these various routes. All of this results in neuronal death and malfunction. A variety of clinical presentations, including subtle appearances of symptoms at different stages of its natural history, are what define CAN. Nerve length has an inverse association with the progression of nervous system injury, with the vagus nerve being impacted first. Sympathetic predominance results from parasympathetic system failure in early illness. Clinically, this manifests as tachycardia at rest. A failure to react appropriately to physiological stresses, such as exercise, is a result of advanced CAN, which causes a constant heart rate. Exercise intolerance is the clinical manifestation of this reduced response.

• #36 Correlation of staging and risk factors with cardiovascular autonomic neuropathy in patients with type II diabetes mellitus | Scientific Reports

  https://www.nature.com/articles/s41598-021-80962-w

  CAN prevalence increases substantially with diabetes duration in T2DM (up to 60% after 15 years). […] Moreover, data validates an association between CAN and glucose variability, specifically in the hypoglycemic category. […] The poorer glycemic control and the longer the duration of the disease, the higher the prevalence of CAN in T2DM. […] Age, duration of disease, WHR, and HbA1c are well correlated with the severity of CAN. […] Parasympathetic impairment is more sensitive to the detection of autonomic dysfunctions than do sympathetic impairment. […] This tendency of people with diabetes to develop CAN is attributed to complex interactions between several mechanisms and pathways leading to neuronal ischemia and finally neuronal death. […] Hyperglycemia is the leading cause of diabetes-related CAN.

• #37 Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

  https://www.e-dmj.org/journal/view.php?number=372

  Diabetic autonomic neuropathy (DAN) is one of the major diabetic complications, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). […] The first reason is that DAN is a systemic disease that involves every organ in the body by affecting the entire autonomic nervous system (ANS) and it leads to increase in morbidity and mortality. […] DAN includes both parasympathetic and sympathetic nerve dysfunction in both T1DM and T2DM patients. […] The explanation for these discrepancies might be that parasympathetic nerve function is more severely affected in T2DM patients. […] As parasympathetic nerve damage seemed to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was like Ewing’s concept.

• #38 Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis

  https://www.mdpi.com/1422-0067/25/4/2296

  Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. […] AAG was discovered by Vernino and colleagues in 2000 to be caused by autoantibodies to the ganglionic nicotinic acetylcholine receptor (gAChR), prior to which the disorder was called acute pandysautonomia. […] The key to the differential diagnosis of peripheral neuropathies presenting with autonomic dysfunction is the combination of detailed history taking, a thorough assessment of the findings of the neurological examination, and comprehensive laboratory examinations. […] Whether Abs against nAChRα3 are actually pathogenic in human AAG is an important issue. […] The EPSP amplitude recovered by day 7, despite the persistence of gAChR antibodies in the mouse serum.

• #39 Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis

  https://www.mdpi.com/1422-0067/25/4/2296

  Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. […] AAG was discovered by Vernino and colleagues in 2000 to be caused by autoantibodies to the ganglionic nicotinic acetylcholine receptor (gAChR), prior to which the disorder was called acute pandysautonomia. […] The key to the differential diagnosis of peripheral neuropathies presenting with autonomic dysfunction is the combination of detailed history taking, a thorough assessment of the findings of the neurological examination, and comprehensive laboratory examinations. […] Whether Abs against nAChRα3 are actually pathogenic in human AAG is an important issue. […] The EPSP amplitude recovered by day 7, despite the persistence of gAChR antibodies in the mouse serum.

• #40 Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis

  https://www.mdpi.com/1422-0067/25/4/2296

  The conceivable mechanism is that the nAChR Abs affect synaptic transmission in autonomic ganglia in the following three-step process: (1) Abs binding to the nAChR; (2) accelerated internalization and degradation of AChR molecules crosslinked by Abs, which leads to reduced numbers of nAChR; and (3) Abs binding to the nAChR cause a functional block of the nAChR. […] The agonistic effects of gAChR autoantibodies need further physiological investigation in the future. […] The pathogenic mechanisms underlying this variability are not yet clear. […] The presence of autoantibodies to autonomic nervous system-related receptors, especially GPCRs, in long COVID has attracted attention.

• #41 Autonomic Neuropathies – Brain, Spinal Cord, and Nerve Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/autonomic-nervous-system-disorders/autonomic-neuropathies

  Autonomic neuropathies are disorders affecting the peripheral nerves that automatically (without conscious effort) regulate body processes (autonomic nerves). […] Autonomic neuropathies are a type of peripheral neuropathy, a disorder in which peripheral nerves are damaged throughout the body. In autonomic neuropathies, there is much more damage to the autonomic nerves than to the somatic nerves. […] Viral infections may trigger an autoimmune reaction that results in destruction of autonomic nerves. […] Some of the antibodies produced by the immune system attack the surface of a nerve fiber or the tissues that wrap around the fiber and enable it to conduct impulses quickly and accurately. […] Sometimes antibodies produced by the immune system attack acetylcholine receptors (the part of nerve cells that enables them to respond to acetylcholine). […] Neuropathies due to an autoimmune reaction are sometimes treated with medications that suppress the immune system (immunosuppressants) and lessen the reaction.

• #42 Cardiovascular autonomic neuropathy in chronic kidney disease: a study of kidney biopsy cases | BMC Nephrology | Full Text

  https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03879-2

  The interplay between cardiac and kidney functions is mediated by the autonomic nervous system. Cardiovascular autonomic neuropathy (CAN) is a well-documented dysfunction of this system, with heart rate variability (HRV) serving as the principal diagnostic tool. […] However, the pathogenesis of CAN in patients with nondiabetic chronic kidney disease (CKD) remains underexplored. […] The prevalence of CAN diagnosed using the CVRR in this nondiabetic CKD cohort was 9.7%, which is four times higher than that in healthy individuals. Nondiabetic CKD patients with CAN was associated with advanced IF/TA. […] The current study aimed to elucidated the prevalence of CAN and evaluate the clinicopathological features associated with CAN in patients with nondiabetic CKD. […] These findings underscore the significant interconnection between CAN and tubulointerstitial damage in the renal pathology of nondiabetic CKD patients.

• #43 Cardiovascular autonomic neuropathy in chronic kidney disease: a study of kidney biopsy cases | BMC Nephrology | Full Text

  https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03879-2

  The interplay between cardiac and kidney functions is mediated by the autonomic nervous system. Cardiovascular autonomic neuropathy (CAN) is a well-documented dysfunction of this system, with heart rate variability (HRV) serving as the principal diagnostic tool. […] However, the pathogenesis of CAN in patients with nondiabetic chronic kidney disease (CKD) remains underexplored. […] The prevalence of CAN diagnosed using the CVRR in this nondiabetic CKD cohort was 9.7%, which is four times higher than that in healthy individuals. Nondiabetic CKD patients with CAN was associated with advanced IF/TA. […] The current study aimed to elucidated the prevalence of CAN and evaluate the clinicopathological features associated with CAN in patients with nondiabetic CKD. […] These findings underscore the significant interconnection between CAN and tubulointerstitial damage in the renal pathology of nondiabetic CKD patients.

• #44 Cardiovascular autonomic neuropathy in chronic kidney disease: a study of kidney biopsy cases | BMC Nephrology | Full Text

  https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03879-2

  The interplay between cardiac and kidney functions is mediated by the autonomic nervous system. Cardiovascular autonomic neuropathy (CAN) is a well-documented dysfunction of this system, with heart rate variability (HRV) serving as the principal diagnostic tool. […] However, the pathogenesis of CAN in patients with nondiabetic chronic kidney disease (CKD) remains underexplored. […] The prevalence of CAN diagnosed using the CVRR in this nondiabetic CKD cohort was 9.7%, which is four times higher than that in healthy individuals. Nondiabetic CKD patients with CAN was associated with advanced IF/TA. […] The current study aimed to elucidated the prevalence of CAN and evaluate the clinicopathological features associated with CAN in patients with nondiabetic CKD. […] These findings underscore the significant interconnection between CAN and tubulointerstitial damage in the renal pathology of nondiabetic CKD patients.

• #45 Cardiovascular autonomic neuropathy in chronic kidney disease: a study of kidney biopsy cases | BMC Nephrology | Full Text

  https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03879-2

  A reduction in the CVRR is indicative of parasympathetic autonomic dysfunction, which subsequently progresses to sympathetic dysfunction. […] Our findings also suggest a trend toward declining kidney function in patients with CAN, highlighting a potential intricate linkage between CAN and CKD progression. […] We propose a deleterious cycle between CKD and CAN mediated by two primary mechanisms: The first involves hyperactivity of the reninangiotensin system (RAS), where elevated urinary angiotensinogen levels are associated with the severity of IF/TA. […] The second mechanism involves the activation of the afferent sympathetic nerves. […] This study has several limitations. First, it was not possible to infer causality between CAN and IF/TA owing to its cross-sectional design. […] The prevalence of CAN diagnosed using the CVRR in patients with nondiabetic CKD was 9.7%, which was four times higher than that in healthy individuals.

• #46 Cardiovascular autonomic neuropathy in chronic kidney disease: a study of kidney biopsy cases | BMC Nephrology | Full Text

  https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03879-2

  A reduction in the CVRR is indicative of parasympathetic autonomic dysfunction, which subsequently progresses to sympathetic dysfunction. […] Our findings also suggest a trend toward declining kidney function in patients with CAN, highlighting a potential intricate linkage between CAN and CKD progression. […] We propose a deleterious cycle between CKD and CAN mediated by two primary mechanisms: The first involves hyperactivity of the reninangiotensin system (RAS), where elevated urinary angiotensinogen levels are associated with the severity of IF/TA. […] The second mechanism involves the activation of the afferent sympathetic nerves. […] This study has several limitations. First, it was not possible to infer causality between CAN and IF/TA owing to its cross-sectional design. […] The prevalence of CAN diagnosed using the CVRR in patients with nondiabetic CKD was 9.7%, which was four times higher than that in healthy individuals.

• #47 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications

  https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm

  Another component that may be associated with the pathogenesis of CAN is OSA. OSA can be defined as a syndrome marked by frequent pauses in breathing during sleep that is usually accompanied by loud snoring, which occurs due to upper airway collapse. Although the exact mechanism remains obscure, this disorder can lead to intermittent hypoxia that increases oxidative stress, contributing to CAN development.

• #48 Autonomic Neuropathies – Neurologic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/neurologic-disorders/autonomic-nervous-system/autonomic-neuropathies

  Autonomic neuropathies are peripheral nerve disorders with disproportionate involvement of autonomic fibers. […] The best known autonomic neuropathies are those accompanying peripheral neuropathy due to diabetes, amyloidosis, or autoimmune disorders. […] Autoimmune autonomic neuropathy is an idiopathic disorder that often develops after a viral infection; onset may be subacute. […] Diagnosis of autonomic neuropathy is based on demonstration of autonomic failure and of a specific cause of neuropathy (eg, diabetes, amyloidosis). […] Autoimmune autonomic neuropathy may be suspected after a viral infection. […] Autoimmune autonomic neuropathy may respond to immunotherapy; plasma exchange or IV gamma-globulin can be used for more severe cases. […] Diagnose based on identifying symptoms due to autonomic failure (eg, orthostatic hypotension, neurogenic bladder, erectile dysfunction, gastroparesis, intractable constipation) and a cause of neuropathy. […] Treat underlying disorders if identified; try immunotherapy if autoimmune autonomic insufficiency is diagnosed or, if symptoms are severe, plasma exchange or IV gamma-globulin.

• #49 Autonomic neuropathy – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/autonomic-neuropathy/symptoms-causes/syc-20369829

  Diabetes, especially when poorly controlled, is the most common cause of autonomic neuropathy. Diabetes can gradually cause nerve damage throughout the body. […] Autoimmune diseases, in which your immune system attacks and damages parts of your body, including your nerves. Examples include Sjogren syndrome, systemic lupus erythematosus, rheumatoid arthritis and celiac disease. Guillain-Barre syndrome is an autoimmune disease that happens rapidly and can affect autonomic nerves. […] Autonomic neuropathy may also be caused by an immune system attack triggered by some cancers (paraneoplastic syndrome). […] Certain inherited disorders also can cause autonomic neuropathy.

• #50 Autonomic Neuropathy: Causes, Diagnosis, & Prevention

  https://www.healthline.com/health/autonomic-neuropathy

  Damage to the nerves that help your organs and organ systems to function can cause a condition called autonomic neuropathy (AN). This nerve damage disturbs signal processing between the autonomic nervous system and the brain. […] Factors that might cause injury to the autonomic nerves include: alcoholism, diabetes, chronic illnesses, such as HIV or Parkinsons disease, medication, such as chemotherapy drugs, nerve trauma, such as a bruise, burn, or cut, an unusual buildup of protein in your organs, autoimmune disorders, such as lupus, degenerative disorders, such as multiple system atrophy. […] Treatments for AN target the damaged nerves and any underlying condition causing injury to the nerves. Different treatments are available depending on your symptoms.

• #51 Autonomic Dysfunction: Symptoms, Types, and Treatments

  https://www.healthline.com/health/autonomic-dysfunction

  Autonomic dysfunction develops when the nerves of the ANS are damaged. […] This condition is called autonomic neuropathy or dysautonomia. […] Diabetes and Parkinsons disease are two examples of chronic conditions that can lead to autonomic dysfunction. […] Autonomic neuropathy refers to damage to nerves from certain medications, injury, or disease. […] Some diseases causing this neuropathy include: uncontrolled high blood pressure, long-term heavy drinking, diabetes, autoimmune disorders. […] Parkinsons disease can cause orthostatic hypotension and other symptoms of ANS damage.

• #52 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J

  https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251

  According to Pop-Busui et al., diabetes-related CAN results from complex interactions between glycemic control, duration of disease, systolic and diastolic blood pressure, and aging-related neuronal death. Hyperglycemia is thought to be a primary culprit, spurring a cascade of multiple complex mechanisms and pathways that induce oxidative stress and toxic glycosylation products ultimately resulting in neuronal dysfunction and death. Hyperglycemia increases mitochondrial production of free reactive oxygen species, thereby causing oxidative damage to the microvasculature supplying these peripheral nerves. […] However, the full pathogenesis of CAN is not clearly understood since the mechanisms involved in its development have only been studied in somatic models and extrapolated to the autonomic nervous system.

• #53 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications

  https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm

  CAN results from lesions of the autonomic nerve fibers that innervate the heart and blood vessels, promoting abnormalities in cardiovascular autonomic control. The mechanisms of autonomic dysfunction are complex and multifactorial, involving degenerative, inflammatory, ischemic, and metabolic abnormalities, which compromise the intrinsic cardiac innervation as well as other structures of the autonomic nervous system. […] Chronic increased oxidative stress has a dangerous impact on the autonomic fibers and pancreatic cells, triggering the insulin resistance process and the development of type 2 diabetes mellitus. In addition, the increase in oxidative stress is associated not only with the progression of diabetes, but also with dyslipidemia, atherosclerosis, cancer, and cardiovascular diseases.

• #54 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications

  https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm

  Cardiovascular autonomic neuropathy (CAN) is a microvascular complication defined as the impairment of cardiovascular autonomic control in persons with diabetes, with no other causes. The etiology of CAN is multifactorial, and several conditions are associated with CAN, such as hyperglycemia, insulin resistance, prediabetes, obesity, hypertension, dyslipidemia, metabolic syndrome, and obstructive sleep apnea (OSA). However, it is mainly recognized as a major complication of type 1 and type 2 diabetes mellitus, since diabetic neuropathies are the most prevalent chronic microvascular complications of diabetes. […] The pathophysiological mechanism responsible for this lesion is multifactorial. Although the mechanisms associated with CAN development remain uncertain in their entirety, the main mechanism is hyperglycemia. Hyperglycemia directly favors an increase in the production of reactive oxygen species (ROS) and advanced glycation end products (AGEs), which are a heterogeneous group of compounds.

• #55

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. […] Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. […] The precise pathophysiology of CAN remains unclear; however, multiple pathways leading to microvascular complications have been identified: AGE-mediated inflammation, increased oxidative stress and reactive oxygen species causing direct nerve cell damage, activation of the hexosamine, protein kinase C and polyol pathways and subsequent osmotic and oxidative stress, and neuronal ischaemia due to diabetic microangiopathy. […] More recently, mitochondrial dysfunction, lipid metabolites in early-onset type 2 diabetes and collagen turnover in type 1 diabetes have been investigated and are emerging pathophysiological pathways in diabetic autonomic neuropathy.

• #56 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J

  https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251

  Diabetes triggers multiple reactions that promote neuropathic changes, such as advanced glycosylation end products from glycation of proteins, activation of poly(ADP ribose) polymerase reductase pathways, direct DNA damage, negative effects on neuronal regeneration and repair, reduced neurotransmitter release and synapse function, altered Na/K/ATPase pump, and damage to endoplasmic reticulum that activates apoptotic pathways. […] Microvascular changes of diabetes, including retinopathy and albuminuria, are associated with progression of CAN based on the results from the EURODIAB study. Increased production of cytokines such as interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as well as inflammation in general, are known to be associated with CAN. […] Just like the somatic neuropathies, diabetes affects autonomic nerves in a length-dependent fashion. As a result, CAN often first manifests in the vagus nerve, the body’s longest parasympathetic autonomic nerve and the one responsible for almost three-quarters of parasympathetic activity; damage to the vagus nerve causes resting tachycardia and an overall decrease in parasympathetic tone. In the later stages of CAN, sympathetic denervation occurs, starting from the apex of the ventricles to the base of the heart.

• #57 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J

  https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251

  Diabetes triggers multiple reactions that promote neuropathic changes, such as advanced glycosylation end products from glycation of proteins, activation of poly(ADP ribose) polymerase reductase pathways, direct DNA damage, negative effects on neuronal regeneration and repair, reduced neurotransmitter release and synapse function, altered Na/K/ATPase pump, and damage to endoplasmic reticulum that activates apoptotic pathways. […] Microvascular changes of diabetes, including retinopathy and albuminuria, are associated with progression of CAN based on the results from the EURODIAB study. Increased production of cytokines such as interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as well as inflammation in general, are known to be associated with CAN. […] Just like the somatic neuropathies, diabetes affects autonomic nerves in a length-dependent fashion. As a result, CAN often first manifests in the vagus nerve, the body’s longest parasympathetic autonomic nerve and the one responsible for almost three-quarters of parasympathetic activity; damage to the vagus nerve causes resting tachycardia and an overall decrease in parasympathetic tone. In the later stages of CAN, sympathetic denervation occurs, starting from the apex of the ventricles to the base of the heart.

• #58 Cardiac autonomic neuropathy in patients with diabetes mellitus: curre | DMSO

  https://www.dovepress.com/cardiac-autonomic-neuropathy-in-patients-with-diabetes-mellitus-curren-peer-reviewed-fulltext-article-DMSO

  CAN might occur as a result of autoimmune autonomic ganglionopathy. This is where autonomic failure occurs in the presence of antibodies to the nicotinic acetylcholine receptor of autonomic ganglia, leading to severe autonomic manifestations. […] Several genes have been linked to the development and progression of diabetic polyneuropathy and CAN, among which are TCF7L2, APOE, and ACE. […] Inflammation plays an important role in the pathogenesis of diabetes and its related micro- and macrovascular complications. CAN has been associated with increased inflammatory markers such as CRP, IL6, and TNF, and adipose-tissue inflammation.

• #59 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J

  https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251

  Diabetes triggers multiple reactions that promote neuropathic changes, such as advanced glycosylation end products from glycation of proteins, activation of poly(ADP ribose) polymerase reductase pathways, direct DNA damage, negative effects on neuronal regeneration and repair, reduced neurotransmitter release and synapse function, altered Na/K/ATPase pump, and damage to endoplasmic reticulum that activates apoptotic pathways. […] Microvascular changes of diabetes, including retinopathy and albuminuria, are associated with progression of CAN based on the results from the EURODIAB study. Increased production of cytokines such as interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as well as inflammation in general, are known to be associated with CAN. […] Just like the somatic neuropathies, diabetes affects autonomic nerves in a length-dependent fashion. As a result, CAN often first manifests in the vagus nerve, the body’s longest parasympathetic autonomic nerve and the one responsible for almost three-quarters of parasympathetic activity; damage to the vagus nerve causes resting tachycardia and an overall decrease in parasympathetic tone. In the later stages of CAN, sympathetic denervation occurs, starting from the apex of the ventricles to the base of the heart.

• #60 Autonomic Neuropathy Pathophysiology – Acibadem Health Point – ACIBADEM Hospitals – Acibadem Health Group

  https://www.acibademhealthpoint.com/autonomic-neuropathy-pathophysiology/

  Inflammation is a big part of making autonomic neuropathy worse. It happens when the immune system overreacts. This can make nerve damage even worse and slow down healing. […] Understanding how inflammation, the immune system, and nerves work together is key to finding new treatments. […] These mechanisms show why treating autonomic neuropathy needs a full approach. By fixing the biochemical issues and stopping nerve fiber loss and pain, doctors can help more. This way, they can lessen the effects of this condition.

• #61 Autonomic Neuropathy Pathophysiology – Acibadem Health Point – ACIBADEM Hospitals – Acibadem Health Group

  https://www.acibademhealthpoint.com/autonomic-neuropathy-pathophysiology/

  Autonomic neuropathy hurts the nerves that control things we don’t think about. It’s a big part of autonomic nervous system disorders. It affects many body functions. […] This condition changes nerve structure and blood flow. It also messes with the immune system. […] Autonomic neuropathy changes the way our nervous system works. It affects how our internal organs work. This needs careful study by experts. […] Nerve damage is a big problem in autonomic neuropathy. This includes axonal degeneration and demyelination. These issues stop electrical signals from moving right. […] When nerves don’t work right, organs can’t do their job well. The heart might beat irregularly, and the bladder could have trouble storing or releasing urine. The digestive system might also have trouble moving food or making digestive juices.

• #62 Autonomic Neuropathy Pathophysiology – Acibadem Health Point – ACIBADEM Hospitals – Acibadem Health Group

  https://www.acibademhealthpoint.com/autonomic-neuropathy-pathophysiology/

  Autonomic neuropathy hurts the nerves that control things we don’t think about. It’s a big part of autonomic nervous system disorders. It affects many body functions. […] This condition changes nerve structure and blood flow. It also messes with the immune system. […] Autonomic neuropathy changes the way our nervous system works. It affects how our internal organs work. This needs careful study by experts. […] Nerve damage is a big problem in autonomic neuropathy. This includes axonal degeneration and demyelination. These issues stop electrical signals from moving right. […] When nerves don’t work right, organs can’t do their job well. The heart might beat irregularly, and the bladder could have trouble storing or releasing urine. The digestive system might also have trouble moving food or making digestive juices.

• #63 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J

  https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251

  Diabetes triggers multiple reactions that promote neuropathic changes, such as advanced glycosylation end products from glycation of proteins, activation of poly(ADP ribose) polymerase reductase pathways, direct DNA damage, negative effects on neuronal regeneration and repair, reduced neurotransmitter release and synapse function, altered Na/K/ATPase pump, and damage to endoplasmic reticulum that activates apoptotic pathways. […] Microvascular changes of diabetes, including retinopathy and albuminuria, are associated with progression of CAN based on the results from the EURODIAB study. Increased production of cytokines such as interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as well as inflammation in general, are known to be associated with CAN. […] Just like the somatic neuropathies, diabetes affects autonomic nerves in a length-dependent fashion. As a result, CAN often first manifests in the vagus nerve, the body’s longest parasympathetic autonomic nerve and the one responsible for almost three-quarters of parasympathetic activity; damage to the vagus nerve causes resting tachycardia and an overall decrease in parasympathetic tone. In the later stages of CAN, sympathetic denervation occurs, starting from the apex of the ventricles to the base of the heart.

• #64 Cardiac Autonomic Neuropathy in Diabetes Mellitus: Pathogenesis, Epidemiology, Diagnosis and Clinical Implications: A Narrative Review

  https://www.mdpi.com/2077-0383/14/3/671

  Cardiac autonomic neuropathy (CAN) is arguably among the most frequently disregarded of all the major consequences of diabetes and leads to the cardiovascular autonomic nerve system dysfunction (EDIC). The impairment of cardiovascular autonomic function in individuals with confirmed DM after alternative reasons have been ruled out is known as CAN, according to the Toronto Consensus Panel on Diabetic Neuropathy Subcommittee. About 7% of people with T1D or T2D had CAN identified at diagnosis. For people with DM type 1 and type 2, the risk is thought to rise by roughly 6% and 2% every year, respectively. The prevalence of CAN rises significantly with the length of diabetes, even if it is relatively low in newly diagnosed individuals with T1D. In the DCCT/EDIC cohort, incidence rates of at least 30% were noted over twenty years of diabetes duration. In patients who are diagnosed with T2D, the incidence of CAN also rises with the length of disease and may reach 60% of patients after 15 years. There is disagreement on how gender affects CAN. There were no variations in the frequency of CAN between men (35%) and women (37%), according to the EURODIAB IDDM Complications Study, but according to the ACCORD study, women (4.7%) were more likely than males (2.6%) to have CAN. Autonomic neuropathy was significantly correlated with the duration of diabetes, age, glycated hemoglobin, retinopathy, microalbuminuria, hypoglycemia, ketoacidosis, smoking, low HDL cholesterol, total cholesterol/HDL cholesterol ratio, fasting triglycerides, and diastolic blood pressure. According to the EURODIAB IDDM Complications Study, autonomic neuropathy was linked to a higher risk of cardiovascular disease. Based on the results of multiple epidemiological studies conducted among people with diabetes, those with CAN have a five-fold greater 5-year mortality rate from this significant consequence than people without cardiovascular autonomic dysfunction. Numerous processes and pathways contribute to CAN, which is brought on by intricate interconnections and ultimately results in neuronal ischemia and death. Hyperglycemia is the primary cause of the pathogenic process. Oxidative stress brought on by hyperglycemia and harmful advanced glycosylation products alter endothelium, membrane permeability, and mitochondrial functioning. Several cellular processes, communication between cells and the surrounding matrix, transcription factors, and gene expression are all disrupted by these various routes. All of this results in neuronal death and malfunction. A variety of clinical presentations, including subtle appearances of symptoms at different stages of its natural history, are what define CAN. Nerve length has an inverse association with the progression of nervous system injury, with the vagus nerve being impacted first. Sympathetic predominance results from parasympathetic system failure in early illness. Clinically, this manifests as tachycardia at rest. A failure to react appropriately to physiological stresses, such as exercise, is a result of advanced CAN, which causes a constant heart rate. Exercise intolerance is the clinical manifestation of this reduced response.

• #65 Correlation of staging and risk factors with cardiovascular autonomic neuropathy in patients with type II diabetes mellitus | Scientific Reports

  https://www.nature.com/articles/s41598-021-80962-w

  The impairment of cardiovascular autonomic control among the underdiagnosed complication of diabetes mellitus (DM) with a high prevalence rate of up to 60% in type 2 DM (T2DM). […] Cardiac autonomic neuropathy (CAN) is an independent risk factor for cardiovascular mortality, arrhythmia, silent ischemia, any major cardiovascular event, and heart failure. […] Disease duration and level of glycemic control are amongst the important causative factors which donated to the development of autonomic neuropathy (AN) in T2DM patients. […] In T2DM, AN is still an underdiagnosed cause of morbidity and mortality, particularly when it involves the cardiac functions in terms of cardiac autonomic neuropathy (CAN). […] This CAN result in cardiovascular dysfunction which is accompanied by the progression to myocardial ischemia, coronary artery disease, and stroke.

• #66 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J

  https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251

  According to Pop-Busui et al., diabetes-related CAN results from complex interactions between glycemic control, duration of disease, systolic and diastolic blood pressure, and aging-related neuronal death. Hyperglycemia is thought to be a primary culprit, spurring a cascade of multiple complex mechanisms and pathways that induce oxidative stress and toxic glycosylation products ultimately resulting in neuronal dysfunction and death. Hyperglycemia increases mitochondrial production of free reactive oxygen species, thereby causing oxidative damage to the microvasculature supplying these peripheral nerves. […] However, the full pathogenesis of CAN is not clearly understood since the mechanisms involved in its development have only been studied in somatic models and extrapolated to the autonomic nervous system.

• #67 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J

  https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251

  According to Pop-Busui et al., diabetes-related CAN results from complex interactions between glycemic control, duration of disease, systolic and diastolic blood pressure, and aging-related neuronal death. Hyperglycemia is thought to be a primary culprit, spurring a cascade of multiple complex mechanisms and pathways that induce oxidative stress and toxic glycosylation products ultimately resulting in neuronal dysfunction and death. Hyperglycemia increases mitochondrial production of free reactive oxygen species, thereby causing oxidative damage to the microvasculature supplying these peripheral nerves. […] However, the full pathogenesis of CAN is not clearly understood since the mechanisms involved in its development have only been studied in somatic models and extrapolated to the autonomic nervous system.

• #68 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications

  https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm

  CAN results from lesions of the autonomic nerve fibers that innervate the heart and blood vessels, promoting abnormalities in cardiovascular autonomic control. The mechanisms of autonomic dysfunction are complex and multifactorial, involving degenerative, inflammatory, ischemic, and metabolic abnormalities, which compromise the intrinsic cardiac innervation as well as other structures of the autonomic nervous system. […] Chronic increased oxidative stress has a dangerous impact on the autonomic fibers and pancreatic cells, triggering the insulin resistance process and the development of type 2 diabetes mellitus. In addition, the increase in oxidative stress is associated not only with the progression of diabetes, but also with dyslipidemia, atherosclerosis, cancer, and cardiovascular diseases.

• #69 Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes

  https://www.e-jcpp.org/journal/view.php?number=98

  Clinical studies have demonstrated an increased risk of mortality in patients with autonomic neuropathy. […] In addition to the mechanisms previously discussed, autonomic nervous system dysfunction can impact the cardiovascular system by causing the loss or reversal of the normal nocturnal dip in blood pressure. […] Sympathetic overactivity augments catecholamine toxicity and insulin resistance, initiating a cascade of events including lipotoxicity, reactive oxygen species production, myocardial energy depletion, calcium abnormalities, and increased oxygen consumption. […] Patients with autonomic neuropathy are known to exhibit an increased left ventricular twist and severe torsion of the left ventricle, a condition thought to result from the predominance of radial contraction. […] Furthermore, autonomic dysfunction is associated with increased risks during surgical procedures that require general anesthesia.

• #70 Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes

  https://www.e-jcpp.org/journal/view.php?number=98

  Clinical studies have demonstrated an increased risk of mortality in patients with autonomic neuropathy. […] In addition to the mechanisms previously discussed, autonomic nervous system dysfunction can impact the cardiovascular system by causing the loss or reversal of the normal nocturnal dip in blood pressure. […] Sympathetic overactivity augments catecholamine toxicity and insulin resistance, initiating a cascade of events including lipotoxicity, reactive oxygen species production, myocardial energy depletion, calcium abnormalities, and increased oxygen consumption. […] Patients with autonomic neuropathy are known to exhibit an increased left ventricular twist and severe torsion of the left ventricle, a condition thought to result from the predominance of radial contraction. […] Furthermore, autonomic dysfunction is associated with increased risks during surgical procedures that require general anesthesia.

• #71 Autonomic Neuropathy – NIDDK

  https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/nerve-damage-diabetic-neuropathies/autonomic-neuropathy

  Autonomic neuropathy is damage to nerves that control your internal organs. […] Over time, high blood glucose and high levels of fats, such as triglycerides, in the blood from diabetes can damage your nerves and the small blood vessels that nourish your nerves, leading to autonomic neuropathy. […] Autonomic neuropathy may also cause gastroparesis. Gastroparesis is a disorder that slows or stops the movement of food from your stomach to your small intestine. Gastroparesis can keep your body from absorbing glucose and using insulin properly. These problems can make it hard to manage your blood glucose. […] Autonomic neuropathy can cause hypoglycemia unawareness, meaning that you dont feel the symptoms of low blood glucose. Normally, early symptoms of low blood glucose can include feeling confused, dizzy, hungry, irritable, or nervous. If nerve damage keeps you from feeling these symptoms, you may not take steps to treat your low blood glucose. Without treatment, you may develop severe hypoglycemia, which can cause you to pass out. You will need help right away to deal with severe hypoglycemia.

• #72 Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

  https://www.e-dmj.org/journal/view.php?doi=10.4093/dmj.2015.39.6.461

  This could be explained by basic morphological difference in autonomic nerves. […] Therefore, the order of morphological changes in sympathetic and parasympathetic nerves of various organs in diabetic patients must be evaluated. […] Autonomic dysfunction (e.g., heightened activity of the sympathetic nervous system and suppressed activity of the parasympathetic nervous system) impairs the ability of the ANS to regulate the cardiovascular system, and inflammatory, metabolic and neurological disease processes. […] Therefore, the role of autonomic imbalance and mechanisms in DAN require further exploration. […] The autonomic neuropathic stomach showed decreased mucosal nerve fiber length and volume density, and an altered mucosal nerve fiber innervation pattern in animal diabetes model and human diabetics.

• #73 Diabetic Autonomic Neuropathy | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.diabetic-autonomic-neuropathy.tf4798

  Diabetic autonomic neuropathy is damage to the autonomic nerves caused by diabetes. […] Autonomic neuropathy may affect the nerves that control sweating. […] Damage to the nerves of the stomach and intestines may cause: […] Nerve damage may cause problems with the bladder and sex organs. […] Treatment focuses on managing the symptoms of autonomic neuropathy.

• #74 Autonomic Neuropathy | Stanford Health Care

  https://stanfordhealthcare.org/medical-conditions/brain-and-nerves/autonomic-neuropathy.html

  Autonomic neuropathy refers to damage to the autonomic nervous system, which controls involuntary body functions such as: […] Autonomic neuropathy is not a single condition. Rather, it is a complication or side-effect caused by disrupted signals between the brain and the nervous system. […] Autonomic neuropathy can damage the nerves of the cardiovascular system, affecting heart rate and blood pressure: […] Damage to the nerves of the digestive system can cause: […] A person with autonomic neuropathy can have problems with urination and sexual function: […] Autonomic neuropathy also can affect the pupils of the eyes, causing the eyes to adapt slowly to changing light. […] Damage to the nerves that control sweating means that you may have trouble regulating your body temperature.

• #75 Diabetic Autonomic Neuropathy | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.diabetic-autonomic-neuropathy.tf4798

  Diabetic autonomic neuropathy is damage to the autonomic nerves caused by diabetes. […] Autonomic neuropathy may affect the nerves that control sweating. […] Damage to the nerves of the stomach and intestines may cause: […] Nerve damage may cause problems with the bladder and sex organs. […] Treatment focuses on managing the symptoms of autonomic neuropathy.

• #76 Autonomic Neuropathy | Stanford Health Care

  https://stanfordhealthcare.org/medical-conditions/brain-and-nerves/autonomic-neuropathy.html

  Autonomic neuropathy refers to damage to the autonomic nervous system, which controls involuntary body functions such as: […] Autonomic neuropathy is not a single condition. Rather, it is a complication or side-effect caused by disrupted signals between the brain and the nervous system. […] Autonomic neuropathy can damage the nerves of the cardiovascular system, affecting heart rate and blood pressure: […] Damage to the nerves of the digestive system can cause: […] A person with autonomic neuropathy can have problems with urination and sexual function: […] Autonomic neuropathy also can affect the pupils of the eyes, causing the eyes to adapt slowly to changing light. […] Damage to the nerves that control sweating means that you may have trouble regulating your body temperature.

• #77 Autonomic Neuropathy | Stanford Health Care

  https://stanfordhealthcare.org/medical-conditions/brain-and-nerves/autonomic-neuropathy.html

  Autonomic neuropathy refers to damage to the autonomic nervous system, which controls involuntary body functions such as: […] Autonomic neuropathy is not a single condition. Rather, it is a complication or side-effect caused by disrupted signals between the brain and the nervous system. […] Autonomic neuropathy can damage the nerves of the cardiovascular system, affecting heart rate and blood pressure: […] Damage to the nerves of the digestive system can cause: […] A person with autonomic neuropathy can have problems with urination and sexual function: […] Autonomic neuropathy also can affect the pupils of the eyes, causing the eyes to adapt slowly to changing light. […] Damage to the nerves that control sweating means that you may have trouble regulating your body temperature.

• #78 Reversing Peripheral and Autonomic Neuropathy

  https://www.linkedin.com/pulse/reversing-peripheral-autonomic-neuropathy-reed-dpm-dabfas-fapwca

  Autonomic Gastrointestinal neuropathy symptoms can involve dysphagia, gastroparesis, bladder dysfunction, bloating, nausea and vomiting, diarrhea, constipation, loss of bowel control. […] Autonomic Sudomotor (sweat glands) neuropathy symptoms can involve hyperhidrosis or excessive sweating, pruritus, dry skin, limb hair loss, calluses, and reddened areas. […] Autonomic Endocrine neuropathy symptoms can involve hypoglycemic unawareness. […] Autonomic Cerebral autonomic symptoms can involve sexual dysfunction, difficulty driving at night, depression, anxiety, sleep disorders, loss of food taste, decreased speech frequency and cognitive memory loss. […] Diabetic neuropathy is specific to the neuropathy caused from loss of oxygen to tissues and organs due to small vessel arterioles caused by excessive blood glucose.

• #79 Reversing Peripheral and Autonomic Neuropathy

  https://www.linkedin.com/pulse/reversing-peripheral-autonomic-neuropathy-reed-dpm-dabfas-fapwca

  Autonomic Gastrointestinal neuropathy symptoms can involve dysphagia, gastroparesis, bladder dysfunction, bloating, nausea and vomiting, diarrhea, constipation, loss of bowel control. […] Autonomic Sudomotor (sweat glands) neuropathy symptoms can involve hyperhidrosis or excessive sweating, pruritus, dry skin, limb hair loss, calluses, and reddened areas. […] Autonomic Endocrine neuropathy symptoms can involve hypoglycemic unawareness. […] Autonomic Cerebral autonomic symptoms can involve sexual dysfunction, difficulty driving at night, depression, anxiety, sleep disorders, loss of food taste, decreased speech frequency and cognitive memory loss. […] Diabetic neuropathy is specific to the neuropathy caused from loss of oxygen to tissues and organs due to small vessel arterioles caused by excessive blood glucose.

• #80

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Genetic susceptibility may play a role in the development of diabetic neuropathy, with several genes identified as being involved in endothelial dysfunction, oxidative nitrosative stress and lipid metabolism. […] Further work is essential to identify the molecular and cellular mechanisms involved in the pathogenesis of CAN in terms of both development and progression, with a greater understanding needed of mitochondrial dysfunction and genetics/genomics.

• #81 Cardiac autonomic neuropathy in patients with diabetes mellitus: curre | DMSO

  https://www.dovepress.com/cardiac-autonomic-neuropathy-in-patients-with-diabetes-mellitus-curren-peer-reviewed-fulltext-article-DMSO

  CAN might occur as a result of autoimmune autonomic ganglionopathy. This is where autonomic failure occurs in the presence of antibodies to the nicotinic acetylcholine receptor of autonomic ganglia, leading to severe autonomic manifestations. […] Several genes have been linked to the development and progression of diabetic polyneuropathy and CAN, among which are TCF7L2, APOE, and ACE. […] Inflammation plays an important role in the pathogenesis of diabetes and its related micro- and macrovascular complications. CAN has been associated with increased inflammatory markers such as CRP, IL6, and TNF, and adipose-tissue inflammation.

• #82 Hereditary sensory and autonomic neuropathy type II: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii/

  Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch to the brain. […] In some affected people, the condition may also cause mild abnormalities of the autonomic neurons, which control involuntary body functions such as heart rate, digestion, and breathing. […] The loss of neurons leads to the inability to feel pain, temperature, and touch sensations and to the impairment of the autonomic nervous system seen in people with HSAN2. […] HSAN2A is caused by mutations that affect a particular isoform called the WNK1/HSN2 protein. […] The mutations involved in HSAN2A result in an abnormally short WNK1/HSN2 protein. […] The RETREG1 protein is normally found in sensory and autonomic neurons. […] When the RETREG1 protein is nonfunctional, recycling of the endoplasmic reticulum is impaired. […] The buildup of these structures likely results in death of the neurons.

• #83 Hereditary sensory and autonomic neuropathy type II: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii/

  Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch to the brain. […] In some affected people, the condition may also cause mild abnormalities of the autonomic neurons, which control involuntary body functions such as heart rate, digestion, and breathing. […] The loss of neurons leads to the inability to feel pain, temperature, and touch sensations and to the impairment of the autonomic nervous system seen in people with HSAN2. […] HSAN2A is caused by mutations that affect a particular isoform called the WNK1/HSN2 protein. […] The mutations involved in HSAN2A result in an abnormally short WNK1/HSN2 protein. […] The RETREG1 protein is normally found in sensory and autonomic neurons. […] When the RETREG1 protein is nonfunctional, recycling of the endoplasmic reticulum is impaired. […] The buildup of these structures likely results in death of the neurons.

• #84

  https://link.springer.com/article/10.1007/s10286-019-00611-1

  Autonomic disorders can be the result of autoimmunity. The classic, well-characterized example is autoimmune autonomic ganglionopathy (AAG), in which antibodies against the ganglionic nicotinic acetylcholine receptor impair autonomic transmission, causing autonomic failure, which responds to immunotherapy. […] However, a number of other autoimmune disorders cause autonomic failure through a variety of mechanisms. […] A better understanding of the underlying pathophysiology aids in the judicious use and selection of immunotherapy.

• #85

  https://link.springer.com/article/10.1007/s10286-019-00611-1

  Autonomic disorders can be the result of autoimmunity. The classic, well-characterized example is autoimmune autonomic ganglionopathy (AAG), in which antibodies against the ganglionic nicotinic acetylcholine receptor impair autonomic transmission, causing autonomic failure, which responds to immunotherapy. […] However, a number of other autoimmune disorders cause autonomic failure through a variety of mechanisms. […] A better understanding of the underlying pathophysiology aids in the judicious use and selection of immunotherapy.

• #86 Autonomic Neuropathies – Brain, Spinal Cord, and Nerve Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/autonomic-nervous-system-disorders/autonomic-neuropathies

  Autonomic neuropathies are disorders affecting the peripheral nerves that automatically (without conscious effort) regulate body processes (autonomic nerves). […] Autonomic neuropathies are a type of peripheral neuropathy, a disorder in which peripheral nerves are damaged throughout the body. In autonomic neuropathies, there is much more damage to the autonomic nerves than to the somatic nerves. […] Viral infections may trigger an autoimmune reaction that results in destruction of autonomic nerves. […] Some of the antibodies produced by the immune system attack the surface of a nerve fiber or the tissues that wrap around the fiber and enable it to conduct impulses quickly and accurately. […] Sometimes antibodies produced by the immune system attack acetylcholine receptors (the part of nerve cells that enables them to respond to acetylcholine). […] Neuropathies due to an autoimmune reaction are sometimes treated with medications that suppress the immune system (immunosuppressants) and lessen the reaction.

• #87 Autonomic Neuropathies – Brain, Spinal Cord, and Nerve Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/autonomic-nervous-system-disorders/autonomic-neuropathies

  Autonomic neuropathies are disorders affecting the peripheral nerves that automatically (without conscious effort) regulate body processes (autonomic nerves). […] Autonomic neuropathies are a type of peripheral neuropathy, a disorder in which peripheral nerves are damaged throughout the body. In autonomic neuropathies, there is much more damage to the autonomic nerves than to the somatic nerves. […] Viral infections may trigger an autoimmune reaction that results in destruction of autonomic nerves. […] Some of the antibodies produced by the immune system attack the surface of a nerve fiber or the tissues that wrap around the fiber and enable it to conduct impulses quickly and accurately. […] Sometimes antibodies produced by the immune system attack acetylcholine receptors (the part of nerve cells that enables them to respond to acetylcholine). […] Neuropathies due to an autoimmune reaction are sometimes treated with medications that suppress the immune system (immunosuppressants) and lessen the reaction.

• #88

  https://link.springer.com/article/10.1007/s00125-024-06242-0

  Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. […] Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. […] The precise pathophysiology of CAN remains unclear; however, multiple pathways leading to microvascular complications have been identified: AGE-mediated inflammation, increased oxidative stress and reactive oxygen species causing direct nerve cell damage, activation of the hexosamine, protein kinase C and polyol pathways and subsequent osmotic and oxidative stress, and neuronal ischaemia due to diabetic microangiopathy. […] More recently, mitochondrial dysfunction, lipid metabolites in early-onset type 2 diabetes and collagen turnover in type 1 diabetes have been investigated and are emerging pathophysiological pathways in diabetic autonomic neuropathy.

• #89

  https://journals.lww.com/md-journal/fulltext/2016/04050/autonomic_neuropathy_and_endothelial_dysfunction.90.aspx

  Autonomic neuropathy is one of the most common complications of diabetes mellitus (DM). The etiology of autonomic impairment is not well-understood, yet. […] The cause-effect relationship between inflammation and/or endothelial dysfunction and diabetic autonomic neuropathy needs to be identified. […] To our knowledge, this is the first study to examine the association of endothelial damage and autonomic neuropathy in patients with IGT or T2DM. The significantly higher levels of both vWF and sE-selectin in patients with IGT or T2DM compared to those of healthy controls, indicates marked endothelial dysfunction in these patients. […] However, we did not find an association between the levels of biomarkers of endothelial dysfunction and the autonomic dysfunction measures. This could be, partially, due to the complex mechanisms in the pathogenesis of diabetic autonomic neuropathy. Indeed, it is still not clear, whether the endothelial dysfunction is the cause or the consequence of diabetic autonomic impairment. […] More studies are needed to clarify the disease pathogenesis and its clinical correlates in diabetic autonomic neuropathy.

• #90

  https://journals.lww.com/md-journal/fulltext/2016/04050/autonomic_neuropathy_and_endothelial_dysfunction.90.aspx

  Autonomic neuropathy is one of the most common complications of diabetes mellitus (DM). The etiology of autonomic impairment is not well-understood, yet. […] The cause-effect relationship between inflammation and/or endothelial dysfunction and diabetic autonomic neuropathy needs to be identified. […] To our knowledge, this is the first study to examine the association of endothelial damage and autonomic neuropathy in patients with IGT or T2DM. The significantly higher levels of both vWF and sE-selectin in patients with IGT or T2DM compared to those of healthy controls, indicates marked endothelial dysfunction in these patients. […] However, we did not find an association between the levels of biomarkers of endothelial dysfunction and the autonomic dysfunction measures. This could be, partially, due to the complex mechanisms in the pathogenesis of diabetic autonomic neuropathy. Indeed, it is still not clear, whether the endothelial dysfunction is the cause or the consequence of diabetic autonomic impairment. […] More studies are needed to clarify the disease pathogenesis and its clinical correlates in diabetic autonomic neuropathy.

• #91

  https://journals.lww.com/md-journal/fulltext/2016/04050/autonomic_neuropathy_and_endothelial_dysfunction.90.aspx

  Autonomic neuropathy is one of the most common complications of diabetes mellitus (DM). The etiology of autonomic impairment is not well-understood, yet. […] The cause-effect relationship between inflammation and/or endothelial dysfunction and diabetic autonomic neuropathy needs to be identified. […] To our knowledge, this is the first study to examine the association of endothelial damage and autonomic neuropathy in patients with IGT or T2DM. The significantly higher levels of both vWF and sE-selectin in patients with IGT or T2DM compared to those of healthy controls, indicates marked endothelial dysfunction in these patients. […] However, we did not find an association between the levels of biomarkers of endothelial dysfunction and the autonomic dysfunction measures. This could be, partially, due to the complex mechanisms in the pathogenesis of diabetic autonomic neuropathy. Indeed, it is still not clear, whether the endothelial dysfunction is the cause or the consequence of diabetic autonomic impairment. […] More studies are needed to clarify the disease pathogenesis and its clinical correlates in diabetic autonomic neuropathy.

• #92 Autonomic Neuropathy: Causes, Diagnosis, & Prevention

  https://www.healthline.com/health/autonomic-neuropathy

  Damage to the nerves that help your organs and organ systems to function can cause a condition called autonomic neuropathy (AN). This nerve damage disturbs signal processing between the autonomic nervous system and the brain. […] Factors that might cause injury to the autonomic nerves include: alcoholism, diabetes, chronic illnesses, such as HIV or Parkinsons disease, medication, such as chemotherapy drugs, nerve trauma, such as a bruise, burn, or cut, an unusual buildup of protein in your organs, autoimmune disorders, such as lupus, degenerative disorders, such as multiple system atrophy. […] Treatments for AN target the damaged nerves and any underlying condition causing injury to the nerves. Different treatments are available depending on your symptoms.

• #93 Autonomic neuropathy – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/autonomic-neuropathy/symptoms-causes/syc-20369829

  Autonomic neuropathy occurs when there is damage to the nerves that control automatic body functions. It can affect blood pressure, temperature control, digestion, bladder function and even sexual function. […] The nerve damage affects the messages sent between the brain and other organs and areas of the autonomic nervous system. These areas include the heart, blood vessels and sweat glands. […] Diabetes is the most common cause of autonomic neuropathy. It can also be caused by other health conditions, viral or bacterial infections, or some medications. Symptoms and treatment vary based on which nerves are damaged. […] Many health conditions can cause autonomic neuropathy. It can also be a side effect of treatments for other diseases, such as cancer. Some common causes of autonomic neuropathy include:

• #94 Autonomic peripheral neuropathy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/15811460/

  The autonomic neuropathies are a group of disorders in which the small, lightly myelinated and unmyelinated autonomic nerve fibres are selectively targeted. […] Diabetes is the most common cause of autonomic neuropathy in more developed countries. […] Autonomic neuropathies can also occur as a result of amyloid deposition, after acute infection, as part of a paraneoplastic syndrome, and after exposure to neurotoxins including therapeutic drugs. […] Certain antibodies (eg, anti-Hu and those directed against neuronal nicotinic acetylcholine receptor) are associated with autonomic signs and symptoms. […] There are several familial autonomic neuropathies with autosomal dominant, autosomal recessive, or X-linked patterns of inheritance. […] Autonomic dysfunction can occur in association with specific infections. […] The availability of sensitive and reproducible measures of autonomic function has improved physicians’ ability to diagnose these disorders.

• #95 Reversing Peripheral and Autonomic Neuropathy

  https://www.linkedin.com/pulse/reversing-peripheral-autonomic-neuropathy-reed-dpm-dabfas-fapwca

  Nitroglycerin has a mechanism of action of vasodilatation of the Tunica Media smooth muscle of the small arterioles that increases blood flow to the capillaries responsible for oxygen release to the surrounding tissues. […] This arteriole vasodilatation due to the nitroglycerin reverses the oxygen tissue damage from narrowing of the arteriole lumen due to excessive glucose osmotic swelling or from unknown causes in idiopathic neuropathy. […] Besides nitroglycerin causes the increase release of oxygen from the capillaries to the nerves of the skin, there is also reversal of autonomic neuropathy symptoms in providing increased capillary oxygenation to major organ systems such as the eyes, kidney and brain.

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