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Clinical Manifestations Of Diabetic Neuropathy

Diabetic Neuropathy

Diabetic Neuropathy

Diabetes is the most common cause of neuropathy. Half of all people with diabetes will develop neuropathy. The nerves of the feet are most commonly affected by diabetic neuropathy. The feet are usually numb, although many people also experience significant discomfort and pain. Most people with diabetic neuropathy are unaware that they have nerve damage, until it is picked up on routine screening by their doctor or when they develop complications. Although there is no cure, early diagnosis and treatment can improve quality of life and reduce the risk of further complications. On this page: Neuropathy means damage to the nerves of the peripheral nervous system. Diabetes is the most common cause of neuropathy. It most commonly affects the nerves to the feet and hands, but any nerves can be involved, including those that control internal organs (autonomic nerves). Up to half of all people with diabetes develop neuropathy during the course of their disease. There is no cure. Management aims to ease symptoms and reduce the risk of further complications. Symptoms of diabetic neuropathy Most people with diabetic neuropathy are unaware that they have nerve damage, until it is picked up on routine screening by their doctor. Typical symptoms vary from person to person, but may include one or more of numbness, pins and needles, tingling, discomfort, or weakness, which usually begin in both feet and spread symmetrically up the legs (like stockings). About half of those people with diabetic neuropathy experience significant pain in their feet and increased sensitivity to painful stimuli (known as neuropathic pain or painful neuropathy).Neuropathic pain is often worse at night, and can seriously disrupt sleep patterns. These symptoms can have a major effect on health and wellbeing bec Continue reading >>

Diabetic Neuropathy

Diabetic Neuropathy

1. DIABETICNEUROPATHYDr. Tushar Patil , M.D.Senior Resident, Dept of Neurology,King George’s Medical University, LucknowIndia 2. DEFINITIONAn internationally agreed simple definition of Diabetic neuropathy for clinical practice is“the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” Boulton AJ et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005 Apr;28(4):956-62. 3. A more detailed definition of neuropathy was previously agreed upon at the San Antonio Consensus Conference:“diabetic neuropathy is a descriptive term meaning a demonstrable disorder, either clinically evident or subclinical, that occurs in the setting of diabetes mellitus without other causes for peripheral neuropathy. The neuropathic disorder includes manifestations in the somatic and/or autonomic parts of the peripheral nervous system”American Diabetes Association, American Academy of Neurology: Report and recommendations of the San Antonio Conference on Diabetic Neuropathy (Consensus Statement). Diabetes Care 11:592–597, 1988 4. CHRONIC COMPLICATIONS OFDIABETES MELLITUSMicrovascular Macrovascular Eye disease  Coronary heart diseaseRetinopathy  Peripheral arterial disease (nonproliferative/proliferative)  Cerebrovascular diseaseMacular edema Other Neuropathy  Gastrointestinal (gastroparesis,Sensory and motor (mono- and diarrhea) polyneuropathy)  Genitourinary (uropathy/sexualAutonomic dysfunction) Nephropathy  Dermatologic Infectious  Cataracts  Glaucoma  Periodontal disease  Hearing loss 5. DIABETIC NEUROPATHY:PROBLEM STATEMENT DM risen over past two decades, 30 million in 1985 to 285 million in 2010. IDF projects 438 million Continue reading >>

Diabetic Neuropathies: Diagnosis And Management

Diabetic Neuropathies: Diagnosis And Management

Abstract Introduction: Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Neuropathy is a common and costly complication of both type 1 and type 2 diabetes. The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long-standing disease. There are two main types of diabetic neuropathies, named as sensorimotor and autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia and sensory loss, and autonomic neuropathy may contribute to myocardial infarction, malignant arrhythmia and sudden death. Methods: In this article we reviewed the pathogenesis, clinical manifestations diagnosis and treatment of diabetic neuropathies. Conclusion: Sensorimotor and autonomic neuropathies (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are common in diabetic patients. Apart from strict glycaemic control, no further therapeutic approach exists in the prevention of this phenomenon. Intensive diabetes therapy, intensive multifactorial cardiovascular risk reduction and lifestyle intervention are recommended in patients with cardiovascular autonomic neuropathy. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder; these conditions are hard to manage. The symptomatic treatment of sensory symptoms includes tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin and opioids. Other treatment strategies are not so effective. © 2014 S. Karger AG, Basel Introduction Changes in human behaviour and lifestyle over the last century h Continue reading >>

Diabetic Neuropathydiabetic Neuropathy Symptoms, Causes, Diagnosis, And Treatment

Diabetic Neuropathydiabetic Neuropathy Symptoms, Causes, Diagnosis, And Treatment

Diabetic neuropathy definition and facts Diabetes is thought to damage nerves as a result of prolonged elevated levels of blood glucose. Peripheral neuropathy most commonly causes: Autonomic neuropathy causes symptoms related to dysfunction of an organ system, such as: Diagnosis of diabetic neuropathy is usually done by a clinical exam. There is no cure for diabetic neuropathy, but treatments are available to manage the symptoms. Diabetic nerve pain may be controlled by medications such as tricyclic antidepressants, duloxetine (Cymbalta), or certain antiseizure medications. Keeping tight control of blood sugar levels is the best way to prevent diabetic neuropathy and other complications of diabetes. Diabetic Peripheral Neuropathy: Improve Diabetes Nerve Pain What are the symptoms and signs of diabetic neuropathy? The symptoms and signs of diabetic neuropathy depend upon the type of neuropathy that is present. Signs and symptoms can also vary in severity among affected people. Signs and symptoms of diabetic peripheral neuropathy include: Numbness or tingling of the feet and lower legs Pain or burning sensations Loss of sensation in the feet or lower legs Sometimes, but less commonly, these symptoms can occur in the hands or arms Signs and symptoms of diabetic proximal neuropathy include: Pain, usually on one side, in the hips, buttocks, or thighs Signs and symptoms of diabetic autonomic neuropathy depend upon the organ system that is involved and can include: Feeling full after eating a small amount Inability to empty the bladder completely Decrease in vaginal lubrication in women Rapid resting heartbeat Signs and symptoms of diabetic focal neuropathy also depend upon the location of the affected nerve. The symptoms can appear suddenly. It usually does not cause a long t Continue reading >>

What Is Peripheral Neuropathy?

What Is Peripheral Neuropathy?

Peripheral neuropathy refers to a problem with the peripheral nerves. These nerves send messages from the central nervous system, the brain and the spinal cord to the rest of the body. The peripheral nerves tell the body when, for example, the hands are cold. It can lead to tingling, prickling, numbness, and muscle weakness in various parts of the body. Peripheral neuropathy can affect a range of different nerves, so it can impact a variety of locations in different ways. It can affect a single nerve, or several nerves at the same time. It is also associated with a number of different underlying medical conditions. Sometimes there is no identifiable cause. It affects some 20 million people in the United States (U.S.). Here are some key points about peripheral neuropathy. More detail is in the main article. Neuropathy is a common complication of a number of different medical conditions. It can involve the autonomic nerves, the motor nerves, and the sensory nerves. Sometimes it affects a single nerve or nerve set, for example, in Bell's Palsy, which affects a facial nerve. Physical trauma, repetitive injury, infection, metabolic problems, and exposure to toxins and some drugs are all possible causes. Treatment Treatment either targets the underlying cause, or it aims to provide symptomatic pain relief and prevent further damage. In the case of diabetic neuropathy, addressing high blood sugars can prevent further nerve damage. For toxic causes, removing the exposure to a suspected toxin, or stopping a drug, can halt further nerve damage. Medications can relieve pain and reduce burning, numbness, and tingling. Drug treatment for neuropathic pain Medications that may help include: Opioid painkillers come with warnings about safety risks. Doctors can also prescribe skin patch Continue reading >>

Diabetic Neuropathy: Clinical Manifestations And Current Treatments

Diabetic Neuropathy: Clinical Manifestations And Current Treatments

Go to: Diabetic neuropathy: clinical manifestations Diabetes can impact the peripheral nervous system in a multitude of ways. DSP accounts for such a large proportion of all peripheral nerve manifestations attributed to diabetes that some use the terms diabetic DSP and diabetic neuropathy interchangeably. Patients with DSP typically have numbness, tingling, pain, and/or weakness that begin in the feet and spread proximally in a length-dependent fashion (stocking and glove distribution). The symptoms are symmetric with sensory symptoms more prominent than motor involvement. Many patients with neuropathy experience a sensation of their socks being bunched up or their shoes not fitting correctly. They even have the apparent paradox of numbness and exquisite sensitivity at the same time. Interestingly, which symptom predominates varies dramatically from patient to patient. The constellation of symptoms from DSP creates many down-stream effects that can affect patients’ quality of life, both physical and mental6. DSP associated numbness often causes balance problems which can lead to falls. DSP is one of three main risk factors for falls in patients with diabetes, along with retinopathy and vestibular dysfunction7. In fact, patients with diabetic DSP are 2–3 times more likely to fall than those with diabetes and no neuropathy7. Additionally, patients with severe DSP are at risk for ulcerations and lower extremity amputations, with 15% developing an ulcer during the course of their disease8. Diabetes is the leading cause of lower extremity amputations, with a 15-fold increase in the likelihood of this life-changing complication9. Moreover, 80,000 lower extremity amputations are performed each year in patients with diabetes9. Overall, diabetic DSP can severely affect quali Continue reading >>

Clinical Manifestations And Diagnosis Of Diabetic Polyneuropathy

Clinical Manifestations And Diagnosis Of Diabetic Polyneuropathy

INTRODUCTION There are many forms of diabetic neuropathy including symmetric polyneuropathy, autonomic neuropathy, radiculopathies, mononeuropathies, and mononeuropathy multiplex (table 1). (See "Epidemiology and classification of diabetic neuropathy".) The clinical manifestations and diagnosis of diabetic polyneuropathy, also referred to as diabetic neuropathy, will be reviewed here. The pathogenesis and treatment of this disorder and the characteristics of the other forms of diabetic neuropathy are discussed separately. (See "Pathogenesis and prevention of diabetic polyneuropathy" and "Treatment of diabetic neuropathy".) CLINICAL MANIFESTATIONS Diabetic polyneuropathy is primarily a symmetrical sensory polyneuropathy, initially affecting the distal lower extremities. Ten to 18 percent of patients have evidence of nerve damage at the time their diabetes is diagnosed, suggesting that even early impairment of glucose handling, classified as prediabetes, is associated with neuropathy. With disease progression, sensory loss ascends and, when reaching approximately mid-calf, appears in the hands. This gradual evolution causes the typical "stocking-glove" sensory loss. This pattern reflects preferential damage according to axon length; the longest axons are affected first. Motor involvement with frank weakness occurs in the same pattern, but only later and in more severe cases. Symptoms and signs — The earliest signs of diabetic polyneuropathy probably reflect the gradual loss of integrity of both large myelinated and small myelinated and unmyelinated nerve fibers: Loss of vibratory sensation and altered proprioception reflect large-fiber loss Continue reading >>

Cardiovascular Autonomic Neuropathy Due To Diabetes Mellitus: Clinical Manifestations, Consequences, And Treatment

Cardiovascular Autonomic Neuropathy Due To Diabetes Mellitus: Clinical Manifestations, Consequences, And Treatment

Context: The aim of this article was to review the importance of the clinical identification of persons with cardiovascular autonomic neuropathy (CAN) and discuss potential treatment interventions. Evidence Acquisition: A MEDLINE search was conducted for articles published during the last 20 yr. In addition, subsequent references of retrieved articles were reviewed. Search strategies included using key terms such as CAN, heart rate variability, orthostatic hypotension, and diabetes mellitus. Evidence Synthesis: CAN is a common form of diabetic autonomic neuropathy and causes abnormalities in heart rate control as well as central and peripheral vascular dynamics. The clinical manifestations of CAN include exercise intolerance, intraoperative cardiovascular lability, orthostatic hypotension, painless myocardial ischemia, and increased risk of mortality. CAN contributes to morbidity, mortality, and reduced quality of life for persons with diabetes. The American Diabetes Association has recently published a statement that provides guidelines for prevention, detection, and management of neuropathy, including CAN, for healthcare providers who care for patients with diabetes. Algorithms for the evaluation and treatment of the patient with CAN, even if the patient is asymptomatic, are provided in this review. Conclusions: Once CAN is identified in a patient with diabetes, healthcare providers may consider altering the prescribed exercise regimen, increasing surveillance for cardiac ischemia, carefully reexamining the list of prescribed medications, and aggressively treating cardiovascular risk factors (e.g. hypertension) that may be associated with the development of CAN. THE AUTONOMIC NERVOUS system modulates the electrical and contractile activity of the myocardium via the i Continue reading >>

Diabetic Neuropathies: Clinical Manifestations And Current Treatment Options

Diabetic Neuropathies: Clinical Manifestations And Current Treatment Options

Diabetic neuropathies: clinical manifestations and current treatment options Dr Aaron Vinik is a Professor of Internal Medicine Pathology, Neurobiology and the Director of Research at the Leonard Strelitz Diabetes Institutes, Eastern Virginia Medical School, Norfolk, VA, USA. He is a physician scientist in interested in identifying problems in the clinic, finding solutions at the bench and translating this into clinical setting. His team discovered the INGAP gene now in clinical trials as a candidate to induce regeneration of pancreatic b cells. He and his team have contributed to the advancements of understanding the pathogenesis and treatment of somatic and automonic neuropathies and helped to develop Standards of Care for the person with neuropathy. Dr Jagdeesh Ullal is a fellow in the Leonard Strelitz Diabetes Institutes, Eastern Virginia Medical School, Norfolk, VA, USA, focusing on acquiring the clinical and scientific knowledge and skills to make him a highly competent clinician and clinical researcher in the field of diabetic neuropathy. Dr Henri Parson is Director of the Neurovascular Unit at the Leonard Strelitz Diabetes Institutes, Eastern Virginia Medical School, Norfolk, VA, USA. She and her team have identified a major neurovascular defect in skin blood flow in people with diabetes and their offspring and shown that African Americans suffer greatly in this regard. She has studiously sought to unravel the mechanisms of this defect in the hope of procuring a logical therapeutic option. Dr Carolina Casellini is a fellow in the Leonard Strelitz Diabetes Institutes, Eastern Virginia Medical School, Norfolk, VA, USA, focusing on acquiring the clinical and scientific knowledge and skills to make her a highly competent clinician and clinical researcher in the fie Continue reading >>

Diabetic Neuropathies: Current Treatment Strategies

Diabetic Neuropathies: Current Treatment Strategies

Diabetic Neuropathies: Current Treatment Strategies Authors: Moderator: Richard S. Beaser, MD; Faculty: Vivian Fonseca, MD; Roy Freeman, MD This accredited activity has been developed for primary care physicians, neurologists, nurse practitioners, physician assistants, nurses, pharmacists, and other clinicians who manage people with diabetes. This activity will explain the pathophysiology, classification, mechanisms, and symptoms of diabetic neuropathies. It will outline current clinical approaches to managing these conditions, along with practical methods for the diagnosis and treatment of diabetic and autonomic neuropathies. Participants will be provided with evidence-based practical and clinically relevant information. At the completion of this activity, the participants should be able to: Recognize the clinical signs and symptoms of the spectrum of neuropathic complications seen in people with diabetes. Prevent or diagnose the painful neuropathic complications of diabetes based on an understanding of their pathophysiology and clinical manifestations. Diagnose and initiate treatment of autonomic neuropathies. Treat patients with diabetic neuropathies using new, effective therapeutic modalities. It is the policy of Joslin Diabetes Center to ensure fair balance, independence, objectivity, and scientific rigor in all programming. All faculty participating in CME activities sponsored by Joslin Diabetes Center are expected to present evidence-based data, identify and reference off-label product use, and disclose all relevant financial relationships existing within the past 12 months with those entities supporting the activity or any others whose products or services are discussed, including: The manufacturer(s) of any commercial products or devices The provider(s) of any Continue reading >>

Diabetic Neuropathy Clinical Presentation: History, Physical Examination, Classification Of Diabetic Neuropathy

Diabetic Neuropathy Clinical Presentation: History, Physical Examination, Classification Of Diabetic Neuropathy

Diabetic NeuropathyClinical Presentation Author: Dianna Quan, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP more... In type 1 diabetes mellitus , distal polyneuropathy typically becomes symptomatic after many years of chronic prolonged hyperglycemia. Conversely, patients with type 2 diabetes mellitus may present with distal polyneuropathy after only a few years of known poor glycemic control; sometimes, these patients already have neuropathy at the time of diagnosis. Since diabetic neuropathy can manifest as a wide variety of sensory, motor, and autonomic symptoms, a structured list of symptoms can be used to help screen all diabetic patients for possible neuropathy. Sensory neuropathy usually is insidious in onset and shows a stocking-and-glove distribution in the distal extremities. Sensory symptoms may be negative or positive, diffuse or focal. Negative sensory symptoms include feelings of numbness or deadness, which patients may describe as being akin to wearing gloves or socks. Loss of balance, especially with the eyes closed, and painless injuries due to loss of sensation are common. Positive symptoms may be described as burning, prickling pain, tingling, electric shocklike feelings, aching, tightness, or hypersensitivity to touch. Motor problems may include distal, proximal, or more focal weakness. In the upper extremities, distal motor symptoms may include impaired fine hand coordination and difficulty with tasks such as opening jars or turning keys. Foot slapping and toe scuffing or frequent tripping may be early symptoms of foot weakness. Symptoms of proximal limb weakness include difficulty climbing up and down stairs, difficulty getting up from a seated or supine position, falls due to the knees giving way, and difficulty raising the arms above the shoul Continue reading >>

What Is Diabetic Neuropathy?

What Is Diabetic Neuropathy?

Diabetes can harm your nerves. That damage, called neuropathy, may be painful. It can happen in several ways, and they all seem to be related to blood sugar levels being too high for too long. To prevent it, work with your doctor to manage your blood sugar. You may hear your doctor mention the four types of diabetes-related neuropathy: peripheral, autonomic, proximal, and focal. Peripheral Neuropathy This type usually affects the feet and legs. Rare cases affect the arms, abdomen, and back. Symptoms include: Tingling Numbness (which may become permanent) Burning (especially in the evening) Pain Early symptoms usually get better when your blood sugar is under control. There are medications to help manage the discomfort. What you should do: Check your feet and legs daily. Use lotion on your feet if they're dry. Take care of your toenails. Ask your doctor if you should go to a podiatrist. Wear shoes that fit well. Wear them all the time, so your feet don't get injured. Autonomic Neuropathy This type usually affects the digestive system, especially the stomach. It can also affect the blood vessels, urinary system, and sex organs. In your digestive system: Symptoms include: Bloating Diarrhea Constipation Heartburn Nausea Vomiting Feeling full after small meals What you should do: You may need to eat smaller meals and take medication to treat it. In blood vessels: Symptoms include: Blacking out when you stand up quickly Faster heartbeat Dizziness Low blood pressure Nausea Vomiting Feeling full sooner than normal If you have it: Avoid standing up too quickly. You may also need to wear special stockings (ask your doctor about them) and take medicine. In Men: Symptoms include: He may not be able to have or keep an erection, or he may have “dry” or reduced ejaculations. What Continue reading >>

Diabetic Peripheral Neuropathy: An Overview

Diabetic Peripheral Neuropathy: An Overview

Diabetic peripheral neuropathy: an overview Jennifer A. Grenell, APRN, CNP, and Anne E. Turner, PA-C Diabetic peripheral neuropathy: an overview Often underreported and undertreated, outcomes can be improved in this condition with appropriate screening and diagnosis. Each month, TheClinical Advisor makes one new clinical feature available ahead of print. Don't forget to take the poll. The results will be published in the next month's issue. Diabetic peripheral neuropathy is a common complication of both type 1 and type 2 diabetes. The overall annual incidence of this condition is approximately 2%, according to the Diabetes Control and Complications Trial.1 Another study estimated that 7% of patients had neuropathy at the time they received a diagnosis of diabetes and that 50% of patients with diabetes for longer than 25 years had peripheral neuropathy.2 A later American study revealed similar findings, estimating that 47% of patients with diabetes eventually develop some sort of peripheral neuropathy.3 Diabetic peripheral neuropathy is a significant source of morbidity and mortality and is implicated in approximately 50% to 75% of nontraumatic amputations.4 It has been defined as "the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes."5 This article presents an overview of diabetic peripheral neuropathy, but it is important to remember that diabetes is not always the cause of nerve dysfunction in patients with diabetes in whom it develops. This article reviews the entities to be considered in the differential diagnosis when a patient with diabetes undergoes an evaluation for peripheral neuropathy; in addition, we review the risk factors for this condition, as well as pathophysiology, signs and Continue reading >>

Diabetic Neuropathy: Clinical Manifestations And Current Treatments

Diabetic Neuropathy: Clinical Manifestations And Current Treatments

Callaghan, Brian C. ; Cheng, Hsinlin T. ; Stables, Catherine L. ; Smith, Andrea L. ; Feldman, Eva L. / Diabetic neuropathy : Clinical manifestations and current treatments . In: The Lancet Neurology . 2012 ; Vol. 11, No. 6. pp. 521-534 @article{ee9f091f5b0c4a5eb071b183b094aee0, title = "Diabetic neuropathy: Clinical manifestations and current treatments", abstract = "Diabetic peripheral neuropathy is a prevalent, disabling disorder. The most common manifestation is distal symmetrical polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control substantially decreases the development of neuropathy in those with type 1 diabetes, the effect is probably much smaller in those with type 2 diabetes. Evidence supports the use of specific anticonvulsants and antidepressants for pain management in patients with diabetic peripheral neuropathy. However, the lack of disease-modifying therapies for diabetic DSP makes the identification of new modifiable risk factors essential. Growing evidence supports an association between components of the metabolic syndrome, including prediabetes, and neuropathy. Studies are needed to further explore this association, which has implications for the development of new treatments for this common disorder.", author = "Callaghan, {Brian C.} and Cheng, {Hsinlin T.} and Stables, {Catherine L.} and Smith, {Andrea L.} and Feldman, {Eva L.}", N2 - Diabetic peripheral neuropathy is a prevalent, disabling disorder. The most common manifestation is distal symmetrical polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control substantially Continue reading >>

Diabetic Neuropathy

Diabetic Neuropathy

Diabetic neuropathies are nerve damaging disorders associated with diabetes mellitus. These conditions are thought to result from a diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum) in addition to macrovascular conditions that can accumulate in diabetic neuropathy. Relatively common conditions which may be associated with diabetic neuropathy include third, fourth, or sixth cranial nerve palsy[1]; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy. Signs and symptoms[edit] Illustration depicting areas affected by diabetic neuropathy Diabetic neuropathy affects all peripheral nerves including sensory neurons, motor neurons, but rarely affects the autonomic nervous system. Therefore, diabetic neuropathy can affect all organs and systems, as all are innervated. There are several distinct syndromes based on the organ systems and members affected, but these are by no means exclusive. A patient can have sensorimotor and autonomic neuropathy or any other combination. Signs and symptoms vary depending on the nerve(s) affected and may include symptoms other than those listed. Symptoms usually develop gradually over years. Symptoms may include the following: Trouble with balance Numbness and tingling of extremities Dysesthesia (abnormal sensation to a body part) Diarrhea Erectile dysfunction Urinary incontinence (loss of bladder control) Facial, mouth and eyelid drooping Vision changes Dizziness Muscle weakness Difficulty swallowing Speech impairment Fasciculation (muscle contractions) Anorgasmia Retrograde ejaculation (in males) Burning or electric pain Pathogenesis[edit] The following factors are thought to be involved in the development of dia Continue reading >>

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