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Muscle & Nerve Jan 2021Autonomic neuropathies represent a complex group of disorders that preferentially target autonomic fibers and can be classified as either acute/subacute or chronic in... (Review)
Review
Autonomic neuropathies represent a complex group of disorders that preferentially target autonomic fibers and can be classified as either acute/subacute or chronic in onset. Acute-onset autonomic neuropathies manifest with such conditions as paraneoplastic syndromes, Guillain-Barre syndrome, Sjögren syndrome, infection, or toxins/chemotherapy. When the presentation is acute, immune-mediated, and without a secondary cause, autoimmune autonomic ganglionopathy is likely, and should be considered for immunotherapy. Of the chronic-onset forms, diabetes is the most widespread and disabling, with autonomic impairment portending increased mortality and cardiac wall remodeling risk. Acquired light chain (AL) and transthyretin (TTR) amyloidosis represent two other key etiologies, with TTR amyloidosis now amenable to newly-approved gene-modifying therapies. The COMPASS-31 questionnaire is a validated outcome measure that can be used to monitor autonomic severity and track treatment response. Symptomatic treatments targeting orthostatic hypotension, among other symptoms, should be individualized and complement disease-modifying therapy, when possible.
Topics: Amyloid Neuropathies, Familial; Autoimmune Diseases of the Nervous System; Autonomic Nervous System; Autonomic Nervous System Diseases; Humans; Peripheral Nervous System Diseases; Prealbumin
PubMed: 32926436
DOI: 10.1002/mus.27048 -
Methodist DeBakey Cardiovascular Journal 2018Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes. The prevalence can range from 2.5% (based on... (Review)
Review
Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes. The prevalence can range from 2.5% (based on the primary prevention cohort in the Diabetes Control and Complications Trial) to as high as 90% of patients with type 1 diabetes. Clinical manifestations range from orthostasis to myocardial infarction. The diagnosis is made using multiple autonomic function tests to assess both sympathetic and parasympathetic function. The pathophysiology of CAN is complex, likely multifactorial, and not completely understood. Treatment is limited to symptomatic control of orthostatic hypotension, which is a late complication, and current strategies to reverse CAN are limited. This review explores the epidemiology, pathophysiology, clinical manifestations, diagnosis, and complications of CAN as well as current treatment options.
Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Heart; Humans; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 30788010
DOI: 10.14797/mdcj-14-4-251 -
Muscle & Nerve Mar 2021Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well-established diagnostic criteria and significant impacts on... (Review)
Review
Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well-established diagnostic criteria and significant impacts on quality of life. Clinical observations, epidemiologic evidence, and animal models of disease have strongly suggested MetS is associated with an elevated risk for cryptogenic sensory peripheral neuropathy (CSPN). MetS neuropathy preferentially affects small unmyelinated axons early in its course, and it may also affect autonomic and large fibers. CSPN risk is linked to MetS and several of its components including obesity, dyslipidemia, and prediabetes. MetS also increases neuropathy risk in patients with established type 1 and type 2 diabetes. In this review we present animal data regarding the role of inflammation and dyslipidemia in MetS neuropathy pathogenesis. Several studies suggest exercise-based lifestyle modification is a promising treatment approach for MetS neuropathy.
Topics: Bariatric Surgery; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diet Therapy; Disease Progression; Dyslipidemias; Exercise; Humans; Hypoglycemic Agents; Metabolic Syndrome; Obesity; Peripheral Nervous System Diseases; Prediabetic State; Risk Factors; Small Fiber Neuropathy; Topiramate
PubMed: 33098165
DOI: 10.1002/mus.27086 -
The Journal of Clinical Investigation Feb 2021The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include... (Review)
Review
The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include motor, secretory, sensory, storage, and excretory functions. Disorders of the nervous system affecting gastrointestinal tract function manifest primarily as abnormalities in motor (rather than secretory) functions. Common gastrointestinal symptoms in neurologic disorders include sialorrhea, dysphagia, gastroparesis, intestinal pseudo-obstruction, constipation, diarrhea, and fecal incontinence. Diseases of the entire neural axis ranging from the cerebral hemispheres to the peripheral autonomic nerves can result in gastrointestinal motility disorders. The most common neurologic diseases affecting gastrointestinal function are stroke, parkinsonism, multiple sclerosis, and diabetic neuropathy. Diagnosis involves identification of the neurologic disease and its distribution, and documentation of segmental gut dysfunction, typically using noninvasive imaging, transit measurements, or intraluminal measurements of pressure activity and coordination of motility. Apart from treatment of the underlying neurologic disease, management focuses on restoration of normal hydration and nutrition and pharmacologic treatment of the gut neuromuscular disorder.
Topics: Diabetic Neuropathies; Enteric Nervous System; Gastrointestinal Diseases; Gastrointestinal Motility; Humans
PubMed: 33586685
DOI: 10.1172/JCI143771 -
Neurological Sciences : Official... Dec 2022Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis is a rare autosomal dominantly inherited disorder caused by mutations in the transthyretin (TTR) gene. The... (Review)
Review
Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis is a rare autosomal dominantly inherited disorder caused by mutations in the transthyretin (TTR) gene. The pathogenetic model of ATTRv amyloidosis indicates that amyloidogenic, usually missense, mutations destabilize the native TTR favouring the dissociation of the tetramer into partially unfolded species that self-assemble into amyloid fibrils. Amyloid deposits and monomer-oligomer toxicity are the basis of multisystemic ATTRv clinical involvement. Peripheral nervous system (autonomic and somatic) and heart are the most affected sites. In the last decades, a better knowledge of pathomechanisms underlying the disease led to develop novel and promising drugs that are rapidly changing the natural history of ATTRv amyloidosis. Thus, clinicians face the challenge of timely diagnosis for addressing patients to appropriate treatment. As well, the progressive nature of ATTRv raises the issue of presymptomatic testing and risk management of carriers. The main aim of this review was to focus on what we know about ATTRv so far, from pathogenesis to clinical manifestations, diagnosis and hence patient's monitoring and treatment, and from presymptomatic testing to management of carriers.
Topics: Humans; Amyloid Neuropathies, Familial; Genetic Testing; Mutation; Prealbumin
PubMed: 33188616
DOI: 10.1007/s10072-020-04889-2 -
Autoimmunity Reviews May 2023In 2011, a syndrome entitled ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants; Shoenfeld's syndrome) was first described. ASIA aimed to organize under a... (Review)
Review
In 2011, a syndrome entitled ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants; Shoenfeld's syndrome) was first described. ASIA aimed to organize under a single umbrella, the existing evidence regarding certain environmental factors which possess immune stimulatory properties, in order to shed light on a common pathway of autoimmune pathogenesis. Such environmental immune stimulators, or adjuvants, include among others: aluminum salts as in vaccines, various medical implants, as well as various infectious agents. After the launch of the ASIA syndrome, the expansion and recognition of this syndrome by different researchers from different countries began. During the past decades, evidence had been accumulating that (auto)immune symptoms can be triggered by exposure to environmental immune stimulatory factors that act as an adjuvant in genetically susceptible individuals. A panoply of unexplained subjective and autonomic-related symptoms has been reported in patients with ASIA syndrome. The current review summarizes and updates accumulated knowledge from the past decades, describing new adjuvants- (e.g. polypropylene meshes) and vaccine- (e.g. HPV and COVID vaccines) induced ASIA. Furthermore, a direct association between inflammatory/autoimmune diseases with ASIA syndrome, will be discussed. Recent cases will strengthen some of the criteria depicted in ASIA syndrome such as clear improvement of symptoms by the removal of adjuvants (e.g. silicone breast implants) from the body of patients. Finally, we will introduce additional factors to be included in the criteria for ASIA syndrome such as: (1) dysregulated non-classical autoantibodies directed against G-protein coupled receptors (GPCRs) of the autonomic nervous system and (2)) small fiber neuropathy (SFN), both of which might explain, at least in part, the development of 'dysautonomia' reported in many ASIA patients.
Topics: Humans; COVID-19; Syndrome; Autoimmune Diseases; Adjuvants, Immunologic; Vaccines
PubMed: 36738954
DOI: 10.1016/j.autrev.2023.103287 -
Biomedicines Nov 2022This article examines the biological, genetic, and environmental aspects of fibromyalgia that may have an impact on its pathogenesis. Symptoms of fibromyalgia may be... (Review)
Review
This article examines the biological, genetic, and environmental aspects of fibromyalgia that may have an impact on its pathogenesis. Symptoms of fibromyalgia may be related to aberrations in the endogenous inhibition of pain as well as changes in the central processing of sensory input. Genetic research has revealed familial aggregation of fibromyalgia and other related disorders like major depressive disorder. Dysfunctional pain processing may also be influenced by exposure to physical or psychological stressors, abnormal biologic reactions in the autonomic nervous system, and neuroendocrine responses. With more research the pathophysiology of fibromyalgia will be better understood, leading to more logical and focused treatment options for fibromyalgia patients.
PubMed: 36551826
DOI: 10.3390/biomedicines10123070 -
Reumatologia 2018Primary Sjögren's syndrome (pSS) is an autoimmune connective tissue disease affecting the exocrine glands, leading to damage of their structure and impairment of their... (Review)
Review
Primary Sjögren's syndrome (pSS) is an autoimmune connective tissue disease affecting the exocrine glands, leading to damage of their structure and impairment of their function. In the course of pSS the internal organs may be involved and the symptoms may concern any system. Neurological disorders are one of the most common extraglandular manifestations of pSS. Available literature data estimate the prevalence of neurological symptoms as about 8.5-70% of patients diagnosed with pSS. The most common neurological complication of pSS is peripheral neuropathy, and in particular sensory polyneuropathy. Central nervous system involvement is much less common. There are also reports of various symptoms connected with damage to cranial nerves and the autonomic nervous system. A careful neurological evaluation, combined with neurophysiological tests, is recommended in patients with pSS. This review summarizes the neurological manifestations of pSS, their possible pathogenic mechanisms, diagnostic evaluation and potential treatment.
PubMed: 29853725
DOI: 10.5114/reum.2018.75521 -
Nature Reviews. Neuroscience Nov 2021The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or... (Review)
Review
The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or regulation of body temperature. Sympathetic regulation of bodily functions requires the establishment and refinement of anatomically and functionally precise connections between postganglionic sympathetic neurons and peripheral organs distributed widely throughout the body. Mechanistic studies of key events in the formation of postganglionic sympathetic neurons during embryonic and early postnatal life, including axon growth, target innervation, neuron survival, and dendrite growth and synapse formation, have advanced the understanding of how neuronal development is shaped by interactions with peripheral tissues and organs. Recent progress has also been made in identifying how the cellular and molecular diversity of sympathetic neurons is established to meet the functional demands of peripheral organs. In this Review, we summarize current knowledge of signalling pathways underlying the development of the sympathetic nervous system. These findings have implications for unravelling the contribution of sympathetic dysfunction stemming, in part, from developmental perturbations to the pathophysiology of peripheral neuropathies and cardiovascular and metabolic disorders.
Topics: Animals; Axons; Dendrites; Humans; Neuronal Plasticity; Neurons; Peripheral Nervous System Diseases; Sympathetic Nervous System
PubMed: 34599308
DOI: 10.1038/s41583-021-00523-y