Diabetic Neuropathy What is NEW Magdy Dahab MD

Diabetic Neuropathy What is NEW? Magdy Dahab, MD UDH Hospital January 23 rd, 2018

Normal Anatomy of a Single Axon The myelinated segments are called internodes. Internode length increases as does the axon diameter. One Schwann cell associated with unmyelinated axons (REMAK cells) may surround more than one axon. The unmyelinated fibers actually outnumber myelinated fibers approximately 4 to 1. M. DAHAB 2 Diabetic Polyneuropathy

Diabetic neuropathy ØDefinition: Presence of symptoms and/or signs of peripheral nerve, plexus, and/or root dysfunction in people with diabetes PN affects 3 to 6% of the population 25% of diabetic patients have painful neuropathy M. DAHAB 3 Diabetic Polyneuropathy

Incidence of Diabetic Neuropathy as a proportion of all diabetics 20 years after diagnosis

Diabetic Neuropathy About 60 -70% of people with diabetes have mild to severe forms of nervous system damage, including: - Impaired sensation or pain in the feet or hands - Slowed digestion of food in the stomach - Carpal tunnel syndrome

Neuropathy in diabetes ►Heterogeneous condition ► It may occur in: proximal or distal nerve fibers Mononeuritis or entrapments involving small or large fibers The somatic or autonomic nervous system M. DAHAB 6 Diabetic Polyneuropathy

Diabetic Peripheral Neuropathy l ‘Dying back’ or ‘length- dependent’ process Longest nerves affected first Ends of nerves preferentially affected l. Typical course Indolent: time course of months to years Gradual, symmetric Symptoms: Predominantly sensory

Diabetic Peripheral Neuropathy Diabetic peripheral neuropathy is a frequent complication of diabetes associated with significant morbidity and mortality Risk factor for ulcers and amputations Impairs quality of life Significant resources are spent to treat patients with DPN Only effective intervention is prevention by tight control of patient’s diabetes M. DAHAB 8 Diabetic Polyneuropathy

Distal Symmetric Polyneuropathy Some persons with distal symmetric polyneuropathy may be asymptomatic, and signs of disease may be detected only by means of a detailed neurologic examination. M. DAHAB 9 Diabetic Polyneuropathy

Diabetic Peripheral Nerve Damage M. DAHAB 10 Diabetic Polyneuropathy

Risk Factors Glucose control Duration of diabetes Damage to blood vessels Mechanical injury to nerves Autoimmune factors Genetic susceptibility Lifestyle factors Smoking Diet M. DAHAB 11 Diabetic Polyneuropathy

Diabetes Distress Diabetes distress Very common and distinct from other psychological disorders Negative psychological reactions Recommendation: Routinely monitor people with diabetes for diabetes distress, particularly when treatment targets are not met and/or at the onset of diabetes complications American Diabetes Association Standards of Medical Care in Diabetes. 12 M. DAHAB Lifestyle Management. Diabetes Care 2017; 40 (Suppl. 1): S 33 -43 Diabetic Polyneuropathy

Pathogenesis 1) Production of destructive metabolic products: Activation of aldose reductase pathway increased sorbitol levels in nervous tissue 2) Protein glycation: Glycosylation of nervous tissue structural proteins destroys the nervous tissue 3) Vascular theory: Glucose deposited in basement membrane decreased permeability build up of toxic metabolites. M. DAHAB 13 Diabetic Polyneuropathy

Sural Nerve Biopsies M. DAHAB 14 Diabetic Polyneuropathy

Classification ØGeneralized/Symmetric Polyneuropathies a. Distal Sensory Polyneuropathy (DSPN) b. Autonomic Neuropathy c. Diabetic neuropathic cachexia (DNC) ØAsymmetric/Focal & Multifocal Neuropathies M. DAHAB a. Diabetic lumbosacral radiculoplexopathy b. Truncal neuropathies (thoracic radiculopathy) c. Cranial neuropathies (facial palsy) 15 Diabetic Polyneuropathy

Diagnosis Symptoms Numbness Tingling Painful Sensations Signs Lost Reflexes, Decreased Sensation Joint Deformity, Skin changes Perception Measures Quantitative Sensory Testing Vibration Detection Threshold Cold Detection Threshold Heat & Pain Threshold Objective Measures M. DAHAB Electrophysiology 16 (Nerve Conduction Studies) Diabetic Polyneuropathy

Clinical Manifestations DPN affects the limbs symmetrically and progresses from distal to proximal over time. DPN is characterized by a stocking and glove distribution: Bilateral symmetrical distribution of signs and symptoms Affects lower limbs first Progresses from distal (toes) to proximal (knee) over time. M. DAHAB 17 Signs and symptoms progress from distal to proximal over time Diabetic Polyneuropathy

Neuropathic Signs Inspection: Dry, atrophic skin, loss of hair and sweating, distal muscle atrophy Sensory (most common): Vibration and proprioception (large fiber) Light touch and pinprick (small fiber) Motor (less common): Distal muscle weakness Reflexes: Absent or depressed M. DAHAB 18 Diabetic Polyneuropathy

Mononeuropathy Peripheral mononeuropathy Single nerve damage due to compression or ischemia Occurs in wrist (carpal tunnel syndrome), elbow, or foot (unilateral foot drop) Symptoms/Signs numbness edema pain M. DAHAB 19 Diabetic Polyneuropathy

Polyradiculopathy Lumbar polyradiculopathy (diabetic amyotrophy) Thigh pain followed by muscle weakness and atrophy Thoracic polyradiculopathy Severe pain on one or both sides of the abdomen, possibly in a band-like pattern Diabetic neuropathic cachexia Polyradiculopathy + peripheral neuropathy Associated with weight loss and depression M. DAHAB 20 Diabetic Polyneuropathy

Diabetic Peripheral Neuropathy is BAD! What is it like to live with neuropathy? “I feel pins and needles in my feet” “My pain is severe and 24/7/365. It has taken my joy out of life. ” “My feet are numb and feel dead” “I’m unsteady when I stand or walk” “I have open sores on my feet” M. DAHAB 21 Diabetic Polyneuropathy

Autonomic neuropathy Affects the autonomic nerves controlling internal organs : Peripheral Genitourinary Gastrointestinal Cardiovascular Is classified as clinical or subclinical based on the presence or absence of symptoms M. DAHAB 22 Diabetic Polyneuropathy

Autonomic Neuropathy Symptomatic v. Postural hypotension v. Diabetic diarrhea v. Neuropathic bladder v. Erectile dysfunction v. Neuropathic edema v. Charcot arthropathy v. Sweating M. DAHAB Subclinical abnormalities o Abnormal pupillary reflexes o Esophageal dysfunction o Abnormal cardiovascular reflexes o Increased peripheral blood flow 23 Diabetic Polyneuropathy

Peripheral Autonomic Dysfunction Contributes to the following symptoms/signs: Neuropathic arthropathy (Charcot foot) Aching, pulsation, tightness, cramping, dry skin, pruritus, edema, sweating abnormalities Weakening of the bones in the foot leading to fractures Testing Direct microelectrode recording of postglanglionic C fibers Galvanic skin responses Measurement of vascular responses M. DAHAB 24 Diabetic Polyneuropathy

Diagnostic Tests Assess symptoms - muscle weakness, muscle cramps, prickling, numbness or pain, vomiting, diarrhea, poor bladder control and sexual dysfunction Comprehensive foot exam Skin sensation and skin integrity X-ray Nerve conduction velocity studies & Electromyographic examination (EMG) M. DAHAB 25 Diabetic Polyneuropathy

Guidelines Recommendations for the management of pain first-line agents: anticonvulsant agents, SNRIs, and other antidepressants M. DAHAB 26 Diabetic Polyneuropathy

Neuropathic pain management Treatment of underlying cause Pharmacological (antidepressant, anticonvulsants, topical agents, analgesics and opioids) Non-pharmacological Lifestyle modification, PT & OT Podiatric care & diabetic orthopedic shoes Pain psychologist & Cognitive Behavioral Rx TENS Complementary & alternative medicine: acupuncture, supplements, etc. Controversial treatments: interventional/regional anesthesia, nerve decompression 27 M. DAHAB spinal cord stimulator, peripheral Diabetic Polyneuropathy

Anticonvulsant Drugs for Diabetic neuropathy carbamazepine phenytoin gabapentin lamotrigine pregabalin M. DAHAB 28 Diabetic Polyneuropathy

Tricyclic Antidepressants: Adverse Effects Commonly reported AEs (generally anticholinergic): Fewest AEs blurred vision cognitive changes constipation dry mouth orthostatic hypotension sedation sexual dysfunction tachycardia urinary retention M. DAHAB AEs = adverse effects. Nortriptyline Imipramine Most AEs 29 Amitriptyline Diabetic Polyneuropathy

Complications of Sensorimotor neuropathy Ulceration (painless) Neuropathic edema Charcot arthropathy Callosities 30 M. DAHAB Diabetic Polyneuropathy

Diabetes Self-Management Education Find a recognized Diabetes Self. Management program Become a recognized DSME program Tools and resources for DSME programs Online education documentation tools M. DAHAB Professional. Diabetes. org/ERP 31 Diabetic Polyneuropathy

Dietary Counseling Core goals: Proper blood glucose management Improve body composition Maintain well-balanced, healthy diet Nutrition support for physical activity Nutritional education for type 2 diabetes and DPN M. DAHAB 32 Diabetic Polyneuropathy

Supervised Exercise Pre – post exercise assessments Vital Signs / Blood glucose level Weekly foot exam Aerobic exercise Start 30 min, 50% max heart rate Resistance exercise Biceps curl, triceps extension, seated row Partial squats, hip abduction, heel raises Balance exercise Tai Chi M. DAHAB 33 Diabetic Polyneuropathy

Home Exercise Teach self assessments Vitals, blood glucose Walking 150 min /week Strength exercises Level of difficulty customized Balance exercises Level of difficulty customized M. DAHAB 34 Diabetic Polyneuropathy

Diabetic Foot Definition: Infection, ulceration or destruction of deep tissues associated with neurological abnormalities & various degrees of peripheral vascular diseases in the lower limb (based on WHO definition) M. DAHAB 35 Diabetic Polyneuropathy

Periphral vascular disease & diabetic PVD q. PVD is the most important factors related to outcome of diabetic foot ulcer q. PVD is diagnosed by simple clinical examination q. Symptoms of ischemia may be masked by neuropathy q. Microangiopathy shouldn't be accepted as primary cause of ulcer q Conservative approach for treatment M. DAHAB 36 Diabetic Polyneuropathy

Epidemiology q 40% - 60% of all non traumatic lower limb amputation q 85% of diabetic related foot amputation are preceded by foot ulcer q 4 out of 5 ulcer in diabetics are precipitated by trauma q 4% -10% is the prevalence of foot ulcer in diabetics M. DAHAB 37 Diabetic Polyneuropathy

How To Prevent Foot Problems 5 corner stones 1. Regular inspection & examination of foot & foot wear 2. Identification of high risk patient 3. Education of patient, family & health care providers 4. Appropriate foot wear 5. Treatment of non ulcerative pathology M. DAHAB 38 Diabetic Polyneuropathy

Conclusion Common DN result in problem sensation in the feet in form of numbness, pain of tingling in feet or legs It develop slowly after many years of diabetes Loss of sensation may increase foot injuries Some cases are associated with weakness in foot muscles Diabetic amyotrophy causes pain, weakness and wasting of thigh muscles Cranial nerves ischemia may result in double vision, drooping eyelid or dizziness Autonomic neuropathy affect blood pressure, digestive tract , bladder function and sexual organs M. DAHAB 39 Diabetic Polyneuropathy

What is NEW? Unerstanding of DN lead to new treatments Woodfield, Aug 2017 We found a way to repair nerve damage Cytokines enable cells to communicate with each other Gp 130 cytokines can enhance peripheral nerve regeneration

What is NEW? News and Research Published on Jan 21 st, 2018 Innovative formulation based on nanotechnology which is designed to relieve chronic neuropathic pain Therapeutic possibilities: Pathogenically & Symptomatic based on glycemic control Alpha-lipoic acid should be first choice among pathogenically oriented treatment regarding aldose reductase inhibitor Antiepileptic (pregabalin & gabapentin) give highest efficacy & lowest adverse events Anti depressant (duloxetine) is extensively used for beneficial effect Combination therapy is applied for treatment of DN by pathogenically oriented & symptomatic treatment

www. magdydahab. com M. DAHAB 42 Diabetic Polyneuropathy