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Biomedicines Mar 2024Many anti-cancer drugs, such as taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors, can cause chemotherapy-induced peripheral neuropathy (CIPN).... (Review)
Review
Many anti-cancer drugs, such as taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors, can cause chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a frequent and harmful side effect that affects the sensory, motor, and autonomic nerves, leading to pain, numbness, tingling, weakness, and reduced quality of life. The causes of CIPN are not fully known, but they involve direct nerve damage, oxidative stress, inflammation, DNA damage, microtubule dysfunction, and altered ion channel activity. CIPN is also affected by genetic, epigenetic, and environmental factors that modulate the risk and intensity of nerve damage. Currently, there are no effective treatments or prevention methods for CIPN, and symptom management is mostly symptomatic and palliative. Therefore, there is a high demand for better understanding of the cellular and molecular mechanisms involved in CIPN, as well as the development of new biomarkers and therapeutic targets. This review gives an overview of the current knowledge and challenges in the field of CIPN, focusing on the biological and molecular mechanisms underlying this disorder.
PubMed: 38672107
DOI: 10.3390/biomedicines12040751 -
Handbook of Clinical Neurology 2024Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality... (Review)
Review
Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality subgroup. Symptoms include weakness, sensory loss, sweating irregularity, blood pressure instability, severe constipation, and neuropathic pain. Neuropathy is the first presenting symptom of malignancy among many patients. The molecular and cellular oncogenic immune targets reside within cell bodies, axons, cytoplasms, or surface membranes of neural tissues. A more favorable immune treatment outcome occurs in those where the targets reside on the cell surface. Patients with antibodies binding cell surface antigens commonly have neural hyperexcitability with pain, cramps, fasciculations, and hyperhidrotic attacks (CASPR2, LGI1, and others). The antigenic targets are also commonly expressed in the central nervous system, with presenting symptoms being myelopathy, encephalopathy, and seizures with neuropathy, often masked. Pain and autonomic components typically relate to small nerve fiber involvement (nociceptive, adrenergic, enteric, and sudomotor), sometimes without nerve fiber loss but rather hyperexcitability. The specific antibodies discovered help direct cancer investigations. Among the primary axonal paraneoplastic neuropathies, pathognomonic clinical features do not exist, and testing for multiple antibodies simultaneously provides the best sensitivity in testing (AGNA1-SOX1; amphiphysin; ANNA-1-HU; ANNA-3-DACH1; CASPR2; CRMP5; LGI1; PCA2-MAP1B, and others). Performing confirmatory antibody testing using adjunct methods improves specificity. Antibody-mediated demyelinating paraneoplastic neuropathies are limited to MAG-IgM (IgM-MGUS, Waldenström's, and myeloma), with the others associated with cytokine elevations (VEGF, IL6) caused by osteosclerotic myeloma, plasmacytoma (POEMS), and rarely angiofollicular lymphoma (Castleman's). Paraneoplastic disorders have clinical overlap with other idiopathic antibody disorders, including IgG4 demyelinating nodopathies (NF155 and Contactin-1). This review summarizes the paraneoplastic neuropathies, including those with peripheral nerve hyperexcitability.
Topics: Humans; Paraneoplastic Polyneuropathy; Multiple Myeloma; Peripheral Nervous System Diseases; Isaacs Syndrome; Autoantibodies; Peripheral Nerves; Immunoglobulin M; Pain
PubMed: 38494281
DOI: 10.1016/B978-0-12-823912-4.00020-7 -
Current Diabetes Reviews Nov 2023Type 2 diabetes mellitus (T2DM) is a worldwide socioeconomic burden, and is accompanied by a variety of metabolic disorders, as well as nerve dysfunction referred to as...
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a worldwide socioeconomic burden, and is accompanied by a variety of metabolic disorders, as well as nerve dysfunction referred to as diabetic neuropathy (DN). Despite a tremendous body of research, the pathogenesis of DN remains largely elusive. Currently, two schools of thought exist regarding the pathogenesis of diabetic neuropathy: a) mitochondrial-induced toxicity, and b) microvascular damage. Both mechanisms signify DN as an intractable disease and, as a consequence, therapeutic approaches treat symptoms with limited efficacy and risk of side effects.
OBJECTIVE
Here, we propose that the human body exclusively employs mechanisms of adaptation to protect itself during an adverse event. For this purpose, two control systems are defined, namely the autonomic and the neural control systems. The autonomic control system responds via inflammatory and immune responses, while the neural control system regulates neural signaling, via plastic adaptation. Both systems are proposed to regulate a network of temporal and causative connections which unravel the complex nature of diabetic complications.
RESULTS
A significant result of this approach infers that both systems make DN reversible, thus opening the door to novel therapeutic applications.
PubMed: 38018186
DOI: 10.2174/0115733998253213231031050044 -
Annual Review of Medicine Jan 2024Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and... (Review)
Review
Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and various forms of autonomic neuropathies involving the cardiovascular, gastrointestinal, and urogenital systems. Prevention or diagnosis in early stages of disease is crucial to prevent symptomatic onset and progression, particularly in the absence of current disease-modifying therapies. In this review, we describe the four main types of diabetic neuropathy. We review current understanding with respect to diagnosis and treatment while highlighting knowledge gaps and future directions.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus
PubMed: 38285516
DOI: 10.1146/annurev-med-043021-033114 -
Diabetes, Obesity & Metabolism Oct 2023
Randomized Controlled Trial
Effects of baricitinib, empagliflozin, linagliptin and telmisartan on cardiovascular autonomic neuropathy in type 1 diabetes: An exploratory, randomized, open-label, crossover trial.
Topics: Humans; Benzhydryl Compounds; Cross-Over Studies; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Linagliptin; Telmisartan; Diabetic Neuropathies
PubMed: 37385968
DOI: 10.1111/dom.15180 -
Brazilian Journal of Cardiovascular... Jul 2023People with type 2 diabetes mellitus present multiple complications and comorbidities, such as peripheral autonomic neuropathies and reduced peripheral force and... (Review)
Review
INTRODUCTION
People with type 2 diabetes mellitus present multiple complications and comorbidities, such as peripheral autonomic neuropathies and reduced peripheral force and functional capacity. Inspiratory muscle training is a widely used intervention with numerous benefits for various disorders. The present study aimed to conduct a systematic review to identify inspiratory muscle training effects on functional capacity, autonomic function, and glycemic indexes in patients with type 2 diabetes mellitus.
METHODS
A search was carried out by two independent reviewers. It was performed in PubMed®, Cochrane Library, Latin American and Caribbean Literature in Health Sciences (or LILACS), Physiotherapy Evidence Database (PEDro), Embase, Scopus, and Web of Science databases. There were no restrictions of language or time. Randomized clinical trials of type 2 diabetes mellitus with inspiratory muscle training intervention were selected. Studies' methodological quality was assessed using PEDro scale.
RESULTS
We found 5,319 studies, and six were selected for qualitative analysis, which was also conducted by the two reviewers. Methodological quality varied - two studies were classified as high quality, two as moderate quality, and two as low quality.
CONCLUSION
It was found that after inspiratory muscle training protocols, there was a reduction in the sympathetic modulation and an increase in functional capacity. The results should be carefully interpreted, as there were divergences in the methodologies adopted, populations, and conclusions between the studies evaluated in this review.
Topics: Humans; Breathing Exercises; Diabetes Mellitus, Type 2; Physical Therapy Modalities; Muscles; Caribbean Region; Muscle Strength; Respiratory Muscles
PubMed: 37403864
DOI: 10.21470/1678-9741-2022-0366 -
Molecular Neurobiology Oct 2023Parkinson's disease is a chronic neuropathy characterised by the formation of Lewy bodies (misfolded alpha-synuclein) in dopaminergic neurons of the substantia nigra and... (Review)
Review
Parkinson's disease is a chronic neuropathy characterised by the formation of Lewy bodies (misfolded alpha-synuclein) in dopaminergic neurons of the substantia nigra and other parts of the brain. Dopaminergic neurons play a vital role in generating both motor and non-motor symptoms. Finding therapeutic targets for Parkinson's disease (PD) is hindered due to an incomplete understanding of the disease's pathophysiology. Existing evidence suggests that the gut microbiota participates in the pathogenesis of PD via immunological, neuroendocrine, and direct neural mechanisms. Gut microbial dysbiosis triggers the loss of dopaminergic neurons via mitochondrial dysfunction. Gut dysbiosis triggers bacterial overgrowth in the small intestine, which increases the permeability barrier and induces systemic inflammation. It results in excessive stimulation of the innate immune system. In addition to that, activation of enteric neurons and enteric glial cells initiates the aggregation of alpha-synuclein. This alpha-synucleinopathy thus affects all levels of the brain-gut axis, including the central, autonomic, and enteric nervous systems. Though the neurobiological signaling cascade between the gut microbiome and the central nervous system is poorly understood, gut microbial metabolites may serve as a promising therapeutic strategy for PD. This article summarises all the known possible ways of bidirectional signal communication, i.e., the "gut-brain axis," where microbes from the middle gut interact with the brain and vice versa, and highlights a unique way to treat neurodegenerative diseases by maintaining homeostasis. The tenth cranial nerve (vagus nerve) plays a significant part in this signal communication. However, the leading regulatory factor for this axis is a diet that helps with microbial colonisation and brain function. Short-chain fatty acids (SCFAs), derived from microbially fermented dietary fibres, link host nutrition to maintain intestinal homeostasis. In addition to that, probiotics modulate cognitive function and the metabolic and behavioural conditions of the body. As technology advances, new techniques will emerge to study the tie-up between gut microbes and neuronal diseases.
PubMed: 37851313
DOI: 10.1007/s12035-023-03691-3 -
Healthcare (Basel, Switzerland) Oct 2023Diabetic neuropathy, including autonomic neuropathy, is a severe complication in patients with poorly controlled diabetes. Specifically, cardiovascular autonomic... (Review)
Review
BACKGROUND
Diabetic neuropathy, including autonomic neuropathy, is a severe complication in patients with poorly controlled diabetes. Specifically, cardiovascular autonomic neuropathy (CAN) plays a significant prognostic role in cardiovascular morbidity and mortality. Exercise, an essential component of diabetes treatment, may have a therapeutic effect on patients with diabetes complicated by CAN. However, it remains unclear whether exercise has a therapeutic or protective effect in diabetes patients with CAN.
METHODS
The author conducted a systematic search of PubMed/MEDLINE, Embase, and The Cochrane Library, resulting in the identification of eight eligible randomized controlled trials for this review.
RESULTS
Exercise, including aerobic exercise combined with resistance training (RT), high-intensity interval training, and progressive RT, has shown a beneficial effect on cardiac autonomic function (CAF) in patients with type 2 diabetes, as measured by heart rate variability, heart rate recovery, and baroreflex sensitivity. However, most studies had low quality. Moreover, there were no relevant studies examining the effect of exercise on CAF in older patients, patients with poorly controlled diabetes, and patients with type 1 diabetes.
CONCLUSIONS
Exercise has the potential to manage patients with CAN by balancing sympathetic and parasympathetic nervous system functions; however, further studies are warranted in the future.
PubMed: 37830705
DOI: 10.3390/healthcare11192668 -
Journal of Yeungnam Medical Science Oct 2023An aging population and changes in dietary habits have increased the incidence of diabetes, resulting in complications such as diabetic foot ulcers (DFUs). DFUs can lead...
An aging population and changes in dietary habits have increased the incidence of diabetes, resulting in complications such as diabetic foot ulcers (DFUs). DFUs can lead to serious disabilities, substantial reductions in patient quality of life, and high financial costs for society. By understanding the etiology and pathophysiology of DFUs, their occurrence can be prevented and managed more effectively. The pathophysiology of DFUs involves metabolic dysfunction, diabetic immunopathy, diabetic neuropathy, and angiopathy. The processes by which hyperglycemia causes peripheral nerve damage are related to adenosine triphosphate deficiency, the polyol pathway, oxidative stress, protein kinase C activity, and proinflammatory processes. In the context of hyperglycemia, the suppression of endothelial nitric oxide production leads to microcirculation atherosclerosis, heightened inflammation, and abnormal intimal growth. Diabetic neuropathy involves sensory, motor, and autonomic neuropathies. The interaction between these neuropathies forms a callus that leads to subcutaneous hemorrhage and skin ulcers. Hyperglycemia causes peripheral vascular changes that result in endothelial cell dysfunction and decreased vasodilator secretion, leading to ischemia. The interplay among these four preceding pathophysiological factors fosters the development and progression of infections in individuals with diabetes. Charcot neuroarthropathy is a chronic and progressive degenerative arthropathy characterized by heightened blood flow, increased calcium dissolution, and repeated minor trauma to insensate joints. Directly and comprehensively addressing the pathogenesis of DFUs could pave the way for the development of innovative treatment approaches with the potential to avoid the most serious complications, including major amputations.
PubMed: 37797951
DOI: 10.12701/jyms.2023.00731 -
Brain and Nerve = Shinkei Kenkyu No... May 2024Autoimmune autonomic ganglionopathy (AAG) and acute autonomic sensory neuropathy (AASN) are immune-mediated neuropathies that affect the autonomic and/or dorsal root... (Review)
Review
Autoimmune autonomic ganglionopathy (AAG) and acute autonomic sensory neuropathy (AASN) are immune-mediated neuropathies that affect the autonomic and/or dorsal root ganglia. Autoantibodies against the nicotinic ganglionic acetylcholine receptor (gAChR) detected in the sera of patients with AAG play a key role in the pathogenesis of this condition. Notably, gAChR antibodies are not detected in the sera of patients with AASN. Currently, AAG and AASN are not considered to be on the same spectrum with regard to disease concept based on clinical symptoms and laboratory findings. However, extra-autonomic brain symptoms (including psychiatric symptoms and personality changes) and endocrine disorders occur in both diseases, which suggests shared pathophysiology between the two conditions.
Topics: Humans; Ganglia, Autonomic; Autoantibodies; Autonomic Nervous System Diseases; Autoimmune Diseases of the Nervous System; Receptors, Nicotinic; Acute Disease; Autoimmune Diseases
PubMed: 38741497
DOI: 10.11477/mf.1416202644