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Current Pain and Headache Reports Jun 2022This narrative review aims to summarize advances in the field of small fiber neuropathy made over the last decade, with emphasis on novel research highlighting the... (Review)
Review
PURPOSE OF REVIEW
This narrative review aims to summarize advances in the field of small fiber neuropathy made over the last decade, with emphasis on novel research highlighting the distinctive features of SFN.
RECENT FINDINGS
While the management of SFNs is ideally aimed at treating the underlying cause, most patients will require pain control via multiple, concurrent therapies. Herein, we highlight the most up-to-date information for diagnosis, medication management, interventional management, and novel therapies on the horizon. Despite the prevalence of small fiber neuropathies, there is no clear consensus on guidelines specific for the treatment of SFN. Despite the lack of specific guidelines for SFN treatment, the most recent general neuropathic pain guidelines are based on Cochrane studies and randomized controlled trials (RCTs) which have individually examined therapies used for the more commonly studied SFNs, such as painful diabetic neuropathy and HIV neuropathy. The recommendations from current guidelines are based on variables such as number needed to treat (NNT), safety, ease of use, and effect on quality of life.
Topics: Diabetic Neuropathies; Humans; Neuralgia; Small Fiber Neuropathy
PubMed: 35384587
DOI: 10.1007/s11916-022-01044-8 -
Current Drug Safety 2021Diabetic peripheral neuropathy (DPN) is traditionally divided into large and small fibre neuropathy (SFN). Damage to the large fibres can be detected using nerve... (Review)
Review
BACKGROUND
Diabetic peripheral neuropathy (DPN) is traditionally divided into large and small fibre neuropathy (SFN). Damage to the large fibres can be detected using nerve conduction studies (NCS) and often results in a significant reduction in sensitivity and loss of protective sensation, while damage to the small fibres is hard to reliably detect and can be either asymptomatic, associated with insensitivity to noxious stimuli, or often manifests itself as intractable neuropathic pain.
OBJECTIVE
To describe the recent advances in both detection, grading, and treatment of DPN as well as the accompanying neuropathic pain.
METHODS
A review of relevant, peer-reviewed, English literature from MEDLINE, EMBASE and Cochrane Library between January 1st 1967 and January 1st 2020 was used.
RESULTS
We identified more than three hundred studies on methods for detecting and grading DPN, and more than eighty randomised-controlled trials for treating painful diabetic neuropathy.
CONCLUSION
NCS remains the method of choice for detecting LFN in people with diabetes, while a gold standard for the detection of SFN is yet to be internationally accepted. In the recent years, several methods with huge potential for detecting and grading this condition have become available including skin biopsies and corneal confocal microscopy, which in the future could represent reliable endpoints for clinical studies. While several newer methods for detecting SFN have been developed, no new drugs have been accepted for treating neuropathic pain in people with diabetes. Tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors and anticonvulsants remain first line treatment, while newer agents targeting the proposed pathophysiology of DPN are being developed.
Topics: Anticonvulsants; Diabetes Mellitus; Diabetic Neuropathies; Humans; Selective Serotonin Reuptake Inhibitors
PubMed: 32735526
DOI: 10.2174/1574886315666200731173113 -
Current Diabetes Reports Aug 2019Diabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain,... (Review)
Review
PURPOSE OF REVIEW
Diabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain, foot ulcers, and lower limb amputation. This review summarizes the epidemiology, risk factors, and management of diabetic peripheral neuropathy and related lower extremity complications.
RECENT FINDINGS
The prevalence of peripheral neuropathy is estimated to be between 6 and 51% among adults with diabetes depending on age, duration of diabetes, glucose control, and type 1 versus type 2 diabetes. The clinical manifestations are variable, ranging from asymptomatic to painful neuropathic symptoms. Because of the risk of foot ulcer (25%) and amputation associated with diabetic peripheral neuropathy, aggressive screening and treatment in the form of glycemic control, regular foot exams, and pain management are important. There is an emerging focus on lifestyle interventions including weight loss and physical activity as well. The American Diabetes Association has issued multiple recommendation statements pertaining to diabetic neuropathies and the care of the diabetic foot. Given that approximately 50% of adults with diabetes will be affected by peripheral neuropathy in their lifetime, more diligent screening and management are important to reduce the complications and health care burden associated with the disease.
Topics: Amputation, Surgical; Cost of Illness; Diabetic Foot; Diabetic Neuropathies; Humans; Lower Extremity; Mass Screening; Risk Factors
PubMed: 31456118
DOI: 10.1007/s11892-019-1212-8 -
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 -
Clinical Therapeutics Jun 2018Diabetic peripheral neuropathy (DPN) is the commonest cause of neuropathy worldwide, and its prevalence increases with the duration of diabetes. It affects approximately... (Review)
Review
PURPOSE
Diabetic peripheral neuropathy (DPN) is the commonest cause of neuropathy worldwide, and its prevalence increases with the duration of diabetes. It affects approximately half of patients with diabetes. DPN is symmetric and predominantly sensory, starting distally and gradually spreading proximally in a glove-and-stocking distribution. It causes substantial morbidity and is associated with increased mortality. The unrelenting nature of pain in this condition can negatively affect a patient's sleep, mood, and functionality and result in a poor quality of life. The purpose of this review was to critically review the current literature on the diagnosis and treatment of DPN, with a focus on the treatment of neuropathic pain in DPN.
METHODS
A comprehensive literature review was undertaken, incorporating article searches in electronic databases (EMBASE, PubMed, OVID) and reference lists of relevant articles with the authors' expertise in DPN. This review considers seminal and novel research in epidemiology; diagnosis, especially in relation to novel surrogate end points; and the treatment of neuropathic pain in DPN. We also consider potential new pharmacotherapies for painful DPN.
FINDINGS
DPN is often misdiagnosed and inadequately treated. Other than improving glycemic control, there is no licensed pathogenetic treatment for diabetic neuropathy. Management of painful DPN remains challenging due to difficulties in personalizing therapy and ascertaining the best dosing strategy, choice of initial pharmacotherapy, consideration of combination therapy, and deciding on defining treatment for poor analgesic responders. Duloxetine and pregabalin remain first-line therapy for neuropathic pain in DPN in all 5 of the major published guidelines by the American Association of Clinical Endocrinologists, American Academy of Neurology, European Federation of Neurological Societies, National Institute of Clinical Excellence (United Kingdom), and the American Diabetes Association, and their use has been approved by the US Food and Drug Administration.
IMPLICATIONS
Clinical recognition of DPN is imperative for allowing timely symptom management to reduce the morbidity associated with this condition.
Topics: Animals; Diabetic Neuropathies; Humans; Neuralgia
PubMed: 29709457
DOI: 10.1016/j.clinthera.2018.04.001 -
European Journal of Pharmacology Aug 2018Diabetic neuropathy is regarded as one of the most debilitating outcomes of diabetes mellitus and may cause pain, decreased motility, and even amputation. Diabetic... (Review)
Review
Diabetic neuropathy is regarded as one of the most debilitating outcomes of diabetes mellitus and may cause pain, decreased motility, and even amputation. Diabetic neuropathy includes multiple forms, ranging from discomfort to death. Prognosis of diabetic neuropathy is an uphill task as it remains silent for several years after the onset of diabetes. Hyperglycemia, apart from inducing oxidative stress in neurons, also leads to activation of multiple biochemical pathways which constitute the major source of damage and are potential therapeutic targets in diabetic neuropathy. A vast array of molecular pathways, including polyol pathway, hexosamine pathway, PKCs signaling, oxidative stress, AGEs pathway, PARP pathway, MAPK pathway, NF-κB signaling, hedgehog pathways, TNF-α signaling, cyclooxygenase pathway, interleukins, lipoxygenase pathway, nerve growth factor, Wnt pathway, autophagy, and GSK3 signaling may be accounted for the pathogenesis and progression of diabetic neuropathy. Although symptomatic treatment is available for diabetic neuropathy, few treatment options are available to eliminate the root cause. The immense physical, psychological, and economic burden of diabetic neuropathy highlights the need for cost effective and targeted therapies. The main aim of this review is to highlight the putative role of various mechanisms and pathways involved in the development of diabetic neuropathy and to impart an in-depth insight on new therapeutic approaches aimed at delaying or reversing various modalities of diabetic neuropathy.
Topics: Animals; Diabetic Neuropathies; Disease Progression; Drug Therapy, Combination; Humans; Hyperglycemia; Incidence; Molecular Targeted Therapy; Neurons; Neuroprotective Agents; Oxidative Stress; Prognosis; Signal Transduction; Treatment Outcome
PubMed: 29966615
DOI: 10.1016/j.ejphar.2018.06.034 -
Neuron Mar 2017Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a... (Review)
Review
Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand the mechanisms underlying diabetic neuropathy (DN). In this review, we present the structural components of the peripheral nervous system that underlie its susceptibility to metabolic insults and then discuss the pathways that contribute to peripheral nerve injury in DN. We also discuss systems biology insights gleaned from the recent advances in biotechnology and bioinformatics, emerging ideas centered on the axon-Schwann cell relationship and associated bioenergetic crosstalk, and the rapid expansion of our knowledge of the mechanisms contributing to neuropathic pain in diabetes. These recent advances in our understanding of DN pathogenesis are paving the way for critical mechanism-based therapy development.
Topics: Animals; Axons; Diabetic Neuropathies; Energy Metabolism; Humans; Models, Neurological; Neuralgia; Peripheral Nervous System; Schwann Cells
PubMed: 28334605
DOI: 10.1016/j.neuron.2017.02.005 -
Primary Care Jun 2022Diabetes-related microvascular complications include diabetic neuropathy (eg, diabetic symmetric polyneuropathy (DSPN), cardiac autonomic neuropathy, gastroparesis,... (Review)
Review
Diabetes-related microvascular complications include diabetic neuropathy (eg, diabetic symmetric polyneuropathy (DSPN), cardiac autonomic neuropathy, gastroparesis, enteropathy, erectile dysfunction, female sexual dysfunction, and hypoglycemia unawareness), diabetic kidney disease (DKD), and diabetes-related eye disease (eg, diabetic retinopathy (DR) and cataract). Both diabetes duration and degree of glycemic control strongly correlate with the development of microvascular complications. The development of diabetes-related microvascular complications interferes with the patient's quality of life and poses higher health system costs. This article will discuss a practical approach to effectively minimize/delay and manage the most common diabetes-related microvascular (DSPN, DKD, and DR).
Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Male; Quality of Life
PubMed: 35595480
DOI: 10.1016/j.pop.2021.11.008 -
Neurologic Clinics Aug 2020Diabetic lumbosacral radiculoplexus neuropathy, also known as diabetic amyotrophy, has a characteristic course of sudden onset of unilateral pain in the thigh and hip,... (Review)
Review
Diabetic lumbosacral radiculoplexus neuropathy, also known as diabetic amyotrophy, has a characteristic course of sudden onset of unilateral pain in the thigh and hip, which may spread to the other side in weeks to months and proceeds with progressive lower extremity weakness, often resulting in the inability to walk unassisted. The syndrome is typically monophasic, and most patients will recover at least to some degree. Less typical features include lack of pain, distal predominant weakness, absence of diabetes, and upper extremity involvement. This article provides a series of interesting cases to highlight the diagnostic challenges and discusses management decision making.
Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus; Diabetic Neuropathies; Female; Humans; Lumbosacral Plexus; Male; Middle Aged; Muscle Weakness; Syndrome
PubMed: 32703468
DOI: 10.1016/j.ncl.2020.03.010 -
Clinical Therapeutics May 2022Neuropathy is one of the most important complications of diabetes. According to recent advances, vitamin D deficiency might play a role in the development and... (Review)
Review
PURPOSE
Neuropathy is one of the most important complications of diabetes. According to recent advances, vitamin D deficiency might play a role in the development and progression of diabetic neuropathy. Moreover, therapeutic vitamin D supplementation has the potential to improve this condition. The aim of the present review was to summarize new data available in this area.
METHODS
The PubMed database was searched for articles written in English and published through September 2021, using combinations of the following key words: vitamin D, diabetes, diabetes mellitus, diabetic neuropathy, polyneuropathy, peripheral neuropathy, cardiac autonomic neuropathy, supplementation, and therapy.
FINDINGS
A number of studies have suggested that vitamin D deficiency can play a significant role in the development of peripheral neuropathy, diabetic foot ulcers, as well as cardiovascular autonomic neuropathy in patients with type 2 diabetes. Vitamin D supplementation might serve as an effective adjuvant therapy for neuropathic pain and may slow or stop the progression of neural damage.
IMPLICATIONS
Vitamin D therapy for diabetic complications could be a reliable option; however, further studies are needed to confirm this notion.
Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 35428527
DOI: 10.1016/j.clinthera.2022.03.012