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Nature Reviews. Disease Primers Jun 2019The global epidemic of prediabetes and diabetes has led to a corresponding epidemic of complications of these disorders. The most prevalent complication is neuropathy,...
The global epidemic of prediabetes and diabetes has led to a corresponding epidemic of complications of these disorders. The most prevalent complication is neuropathy, of which distal symmetric polyneuropathy (for the purpose of this Primer, referred to as diabetic neuropathy) is very common. Diabetic neuropathy is a loss of sensory function beginning distally in the lower extremities that is also characterized by pain and substantial morbidity. Over time, at least 50% of individuals with diabetes develop diabetic neuropathy. Glucose control effectively halts the progression of diabetic neuropathy in patients with type 1 diabetes mellitus, but the effects are more modest in those with type 2 diabetes mellitus. These findings have led to new efforts to understand the aetiology of diabetic neuropathy, along with new 2017 recommendations on approaches to prevent and treat this disorder that are specific for each type of diabetes. In parallel, new guidelines for the treatment of painful diabetic neuropathy using distinct classes of drugs, with an emphasis on avoiding opioid use, have been issued. Although our understanding of the complexities of diabetic neuropathy has substantially evolved over the past decade, the distinct mechanisms underlying neuropathy in type 1 and type 2 diabetes remains unknown. Future discoveries on disease pathogenesis will be crucial to successfully address all aspects of diabetic neuropathy, from prevention to treatment.
Topics: Diabetic Neuropathies; Humans; Quality of Life; Risk Factors
PubMed: 31197183
DOI: 10.1038/s41572-019-0097-9 -
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 -
American Family Physician Dec 2020Peripheral neuropathy, a common neurologic problem encountered by family physicians, can be classified clinically by the anatomic pattern of presenting symptoms and, if...
Peripheral neuropathy, a common neurologic problem encountered by family physicians, can be classified clinically by the anatomic pattern of presenting symptoms and, if indicated, by results of electrodiagnostic studies for axonal and demyelinating disease. The prevalence of peripheral neuropathy in the general population ranges from 1% to 7%, with higher rates among those older than 50 years. Common identifiable causes include diabetes mellitus, nerve compression or injury, alcohol use, toxin exposure, hereditary diseases, and nutritional deficiencies. Peripheral neuropathy is idiopathic in 25% to 46% of cases. Diagnosis requires a comprehensive history, physical examination, and judicious laboratory testing. Early peripheral neuropathy may present as sensory alterations that are often progressive, including sensory loss, numbness, pain, or burning sensations in a "stocking and glove" distribution of the extremities. Later stages may involve proximal numbness, distal weakness, or atrophy. Physical examination should include a comprehensive neurologic and musculoskeletal evaluation. If the peripheral nervous system is identified as the likely source of the patient's symptoms, evaluation for potential underlying etiologies should initially focus on treatable causes. Initial laboratory evaluation includes a complete blood count; a comprehensive metabolic profile; fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels; and serum protein electrophoresis with immunofixation. If the initial evaluation is inconclusive, referral to a neurologist for additional testing (e.g., electrodiagnostic studies, specific antibody assays, nerve biopsy) should be considered. Treatment of peripheral neuropathy focuses on managing the underlying etiology. Several classes of medications, including gabapentinoids and antidepressants, can help alleviate neuropathic pain.
Topics: Diabetic Neuropathies; Diagnosis, Differential; Family Practice; Humans; Medical History Taking; Peripheral Nervous System Diseases; Physical Examination
PubMed: 33320513
DOI: No ID Found -
Journal of Neural Transmission (Vienna,... Apr 2020Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral... (Review)
Review
Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.
Topics: Chronic Pain; Diabetic Neuropathies; Humans; Neuralgia
PubMed: 32036431
DOI: 10.1007/s00702-020-02145-7 -
Pain Sep 2020Neuropathy is a common complication of long-term diabetes that impairs quality of life by producing pain, sensory loss and limb amputation. The presence of neuropathy in... (Review)
Review
Neuropathy is a common complication of long-term diabetes that impairs quality of life by producing pain, sensory loss and limb amputation. The presence of neuropathy in both insulin-deficient (type 1) and insulin resistant (type 2) diabetes along with the slowing of progression of neuropathy by improved glycemic control in type 1 diabetes has caused the majority of preclinical and clinical investigations to focus on hyperglycemia as the initiating pathogenic lesion. Studies in animal models of diabetes have identified multiple plausible mechanisms of glucotoxicity to the nervous system including post-translational modification of proteins by glucose and increased glucose metabolism by aldose reductase, glycolysis and other catabolic pathways. However, it is becoming increasingly apparent that factors not necessarily downstream of hyperglycemia can also contribute to the incidence, progression and severity of neuropathy and neuropathic pain. For example, peripheral nerve contains insulin receptors that transduce the neurotrophic and neurosupportive properties of insulin, independent of systemic glucose regulation, while the detection of neuropathy and neuropathic pain in patients with metabolic syndrome and failure of improved glycemic control to protect against neuropathy in cohorts of type 2 diabetic patients has placed a focus on the pathogenic role of dyslipidemia. This review provides an overview of current understanding of potential initiating lesions for diabetic neuropathy and the multiple downstream mechanisms identified in cell and animal models of diabetes that may contribute to the pathogenesis of diabetic neuropathy and neuropathic pain.
Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Glucose Intolerance; Humans; Neuralgia; Pain; Pain Measurement; Quality of Life
PubMed: 32999525
DOI: 10.1097/j.pain.0000000000001922 -
Brain : a Journal of Neurology Jul 2021Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the... (Review)
Review
Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the course of their disease, which is accompanied by neuropathic pain in 30-40% of cases. Peripheral nerve injury in diabetes can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, and mononeuropathies. The most common diabetic neuropathy is distal symmetric polyneuropathy, which we will refer to as DN, with its characteristic glove and stocking like presentation of distal sensory or motor function loss. DN or its painful counterpart, painful DN, are associated with increased mortality and morbidity; thus, early recognition and preventive measures are essential. Nevertheless, it is not easy to diagnose DN or painful DN, particularly in patients with early and mild neuropathy, and there is currently no single established diagnostic gold standard. The most common diagnostic approach in research is a hierarchical system, which combines symptoms, signs, and a series of confirmatory tests. The general lack of long-term prospective studies has limited the evaluation of the sensitivity and specificity of new morphometric and neurophysiological techniques. Thus, the best paradigm for screening DN and painful DN both in research and in clinical practice remains uncertain. Herein, we review the diagnostic challenges from both clinical and research perspectives and their implications for managing patients with DN. There is no established DN treatment, apart from improved glycaemic control, which is more effective in type 1 than in type 2 diabetes, and only symptomatic management is available for painful DN. Currently, less than one-third of patients with painful DN derive sufficient pain relief with existing pharmacotherapies. A more precise and distinct sensory profile from patients with DN and painful DN may help identify responsive patients to one treatment versus another. Detailed sensory profiles will lead to tailored treatment for patient subgroups with painful DN by matching to novel or established DN pathomechanisms and also for improved clinical trials stratification. Large randomized clinical trials are needed to identify the interventions, i.e. pharmacological, physical, cognitive, educational, etc., which lead to the best therapeutic outcomes.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Neuralgia
PubMed: 33711103
DOI: 10.1093/brain/awab079 -
Journal of Neurology Sep 2022In this update, we review the recent discovery of autosomal recessive variants in sorbitol dehydrogenase as one of the commonest and potentially treatable causes of... (Review)
Review
In this update, we review the recent discovery of autosomal recessive variants in sorbitol dehydrogenase as one of the commonest and potentially treatable causes of hereditary motor neuropathy and CMT2. We also report on recent therapeutic advances in hereditary neuropathy including the use of lipid nanoparticle sequestered antisense oligonucleotides in CMT1A and lipid nanoparticle delivered CRISPR-Cas9 gene editing in ATTR amyloidosis.
Topics: Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Humans; Liposomes; Nanoparticles
PubMed: 35596796
DOI: 10.1007/s00415-022-11164-1 -
Australian Family Physician Mar 2015Paraesthesia reflects an abnormality affecting the sensory pathways anywhere between the peripheral sensory nervous system and the sensory cortex. As with all neurology,... (Review)
Review
BACKGROUND
Paraesthesia reflects an abnormality affecting the sensory pathways anywhere between the peripheral sensory nervous system and the sensory cortex. As with all neurology, the fundamental diagnostic tool is a concise history, devoid of potentially ambiguous jargon, which properly reflects the true nature of what the patient is experiencing, provocateurs, precipitating and relieving factors, concomitant illnesses, such as diabetes, and any treatments that could evoke neuropathies.
OBJECTIVE
Some localised neuropathies, such as carpal tunnel syndrome (CTS) or ulnar neuropathy, produce classical features, such as weakness of the 'LOAF' (lateral two lumbricals, opponens pollicis, abductor pollicis brevis and flexor pollicis brevis) median innervated muscles, thereby obviating need for further neurophysiology. Nerve conduction studies may be necessary to diagnose peripheral neuropathy, but they may also be normal with small fibre neuropathy. Even with a diagnosis of peripheral neuropathy, definition of the underlying cause may remain elusive in a significant proportion of cases, despite involvement of consultants.
DISCUSSION
Treatment is based on the relevant diagnosis and mechanism to address the cause. This includes better glycaemic control for diabetes, night splint for CTS or elbow padding for ulnar neuropathy, modifying lifestyle with reduced alcohol consumption or replacing dietary deficiencies or changing medications where appropriate and practical. Should such intervention fail to relieve symptoms, consideration of intervention to relieve symptoms of neuropathic pain may be required.
Topics: Disease Management; Electrodiagnosis; Humans; Paresthesia; Peripheral Nervous System Diseases
PubMed: 25770571
DOI: No ID Found -
Orthopaedics & Traumatology, Surgery &... Feb 2021At the elbow, the ulnar nerve (UN) may be the site of a static compression (by the cubital tunnel retinaculum and Osborne's ligament between the two heads of the flexor... (Review)
Review
At the elbow, the ulnar nerve (UN) may be the site of a static compression (by the cubital tunnel retinaculum and Osborne's ligament between the two heads of the flexor carpi ulnaris), or a dynamic compression, especially when the nerve is unstable (subluxation/dislocation outside the ulnar groove). The clinical basis for the diagnosis of ulnar neuropathy involves looking for subjective and objective signs of sensory and/or motor deficit in the ulnar nerve's territory in the hand, a pseudo-Tinel's sign, and doing manipulations to provoke UN irritation. The diagnosis is confirmed by electromyography and ultrasonography. In the early stages, patient education and elimination of flexion postures or repeated elbow flexion motions can provide relief. If this fails or signs of sensory and/or motor deficit are present, surgical treatment is proposed. If the nerve is stable, in-situ nerve decompression is typically done as the first-line treatment. If the nerve is unstable, anterior nerve transposition - generally subcutaneous - or more rarely, a medial epicondylectomy can be done. If surgical treatment fails, the patient's history is reviewed, and diagnostic tests can be repeated. Except in cases of a fibrotic scar, the main causes of failure are neuroma of a branch of the medial cutaneous nerve of the forearm, instability of the nerve and persistence of a compression point. In the latter two cases, surgical revision is justified and anterior nerve transposition or epicondylectomy can be proposed.
Topics: Cubital Tunnel Syndrome; Decompression, Surgical; Elbow; Humans; Neurosurgical Procedures; Ulnar Nerve; Ulnar Neuropathies
PubMed: 33321238
DOI: 10.1016/j.otsr.2020.102754