Diabetic Neuropathy

EMEGOAKOR NONSO

Outline• Introduction• Epidemiology• Classification• Risk factors• Pathogenesis• Clinical presentation• Physical examination• Investigations • Staging• Differential diagnosis• Treatment• Prognosis • Conclusion

INTRODUCTION

• Is the presence of symptoms and signs of nervous dysfunction in people with diabetes after exclusion of other causes

• It’s the commonest complication of long standing diabetes

• Up to 50% of diabetics will come down with one form of neuropathy or the other.

Epidemiology

• Up to 70% of people with diabetes will experience neuropathy

• Some form of neuropathy may already be present at time of making a diagnosis of type 2 DM

• 95.7% 0f patients with DFU had neuropathy(Ikem et al 2002

• More than 60% of nontraumatic lower-limb amputations in the United States occur among people with diabetes following neuropathy

Classification of Diabetic Neuropathy

• Somatic polyneuropathy1) Symmetrical sensory neuropathy(distal)2) Asymmetrical motor neuropathy(proximal),

including amyotrophy

• Mononeuropathy and mononeuritis multiplex

• Autonomic neuropathy

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Risk Factors• Poor glycaemic control• Advanced age• Long duration of diabetes• Hypertension• dyslipidaemia• HLA DR3/DR4 phenotype• Smoking• Heavy alcohol intake• Height i.e tall stature

Pathogenesis

• Hyperglycaemia is directly toxic to cells;altering cell growth,gene and protein expression,hence increasing ECM and TGF beta production

• Formation of AGES(advanced glycosylation end products); may disrupt neuronal integrity by stimulation of pro-inflammatory cytokines and complements

Pathogenesis ctd

• Polyol pathway; accumulation of sorbitol and fructose in schwann cells lead to decreased nerve myoinositol,reduced Na-k ATPase activity, impaired axonal transport,abnormal AP propagation and breakdown of nerve structure

• DAG/PKc pathway; pkc alters gene transcription for fibronectin,type 4 collagen,contractile proteins,ECM in the neurones

Pathogenesis

• Oxidative stress; increased free radicals and reactive oxygen species produced in DM cause direct damage to blood vessels(vasa nervorum) leading to nerve ischaemia and hypoxia

• This may be the major pathogenetic mechanism in mononeuropathies

Other mechanisms

• Immune mechanisms• Decreased neurotrophic growth factors• Decreased essential fatty acids• Depletion of ATP by polyADP ribosylation

Symmetrical sensory polyneuropathy

• Most common form of diabetic neuropathy • Affects distal lower extremities and hands

(“stocking-glove” sensory loss) • Symptoms

– Feeling of numbness or deadness– Tingling, prickling,aching, burning sensations– Paresthesia(hyper/hypoasthesia,)– Loss of vibratory sensation– Loss of balance in the dark– Loss of pain sensation

Slides current until 2008

Painless nature of diabetic foot disease

Slides current until 2008

Sensory nerve damage

Asymmetric motor neuropathy

• Proximal muscle weakness(proximal myopathy)• There may be distal involvement too.• DM AMYOTROPHY; painful wasting of quadriceps

femoris.• Neuropathic pain; burning,crawling pain in the

feet,shins and anterior thigh• Worse at night, with hyperaesthesias• No muscle wasting• Resolves with good glucose control

Slides current until 2008

Motor nerve damage

Diabetic Amyotrophy

Cheiroarthropathy

Trigger finger

Mononeuropathy

• Peripheral mononeuropathy– Single nerve damage due to compression or

ischemia – Pain and motor weakness of muscles supplied– Any nerve may be involved– CN 3, 6,7,peroneal nerve e.t.c– Mononeuritis multiplex-Multiple ischemic nerve

damage– Occurs in wrist (carpal tunnel syndrome), elbow, or

foot (unilateral foot drop)

Autonomic neuropathy

• CVS; resting tachycardia, fixed heart rate, orthostatic hypotension, loss of sinus arrhythmia, reduced exercise tolerance silent MI, hypoglycemia unawareness

• GIT; gastroparesis, autonomic diarrhea alternating with constipation, abdominal pain, fecal incontinence, abdominal bloating

Autonomic neuropathy ctd

• Urogenital system; incomplete bladder emptying, stasis, UTI,atonic painless distended bladder; erectile dysfunction and retrograde ejaculation, loss of libido, dyspareunia,

• Sudomotor symptoms; hyperhidrosis, anhidrosis, gustatory sweating, heat intolerance, dry skin

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Physical Examination.

• Inspect feet for features/sequele of neuropathy; callousties, cracks,fissures, interosseous muscle wasting, flattened foot, high arch, claw toe, charcot arthropathy.

• Note following features on hand, wasting of small hand muscles, trigger finger, cheiroarthropathy

Slides current until 2008

Autonomic nerve damage

Slides current until 2008

Localized callus

Complications of Sensorimotor/poly neuropathy

• Ulceration (painless)• Neuropathic edema• Charcot arthropathy• Callosities

NEUROLOGICAL ASSESMENT OF THE FOOTNEUROLOGICAL ASSESMENT OF THE FOOT

• Light touch using cotton wool.• Pin prick• Joint position sense• Vibration sense• Temperature perception- hot & cold• Light pressure using Semmes-Weinstein

monofilament• Deep tendon reflexes.• Heel toe walking test

Screening for Neuropathy

• 128 Hz tuning fork for testing of vibration perception

• 10g Semmers monofilament

The main reason is toidentify patients at riskfor development ofdiabetic foot(LOPS)

Slides current until 2008

Diabetic peripheral neuropathyscreening tests

• Test sensation – Biothesiometer– Tuning fork– 10 gm monofilament

• Ankle reflexes

Diagnosis

Tests for peripheral neuropathy • Light touch and pin prick• Vibration• Deep tendon reflexes• Muscle bulk and power

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Tests for autonomic neuropathy

• Resting heart rate >100bpm• HR variation during deep breathing (6 breaths

per minute)– Max-min > 15bpm (<10 is abnormal)– R-R interval >1.17

• HR response to vasalva-R-R>1,2• <16mmHg diastolic pressure rise during

sustained hand grip• Postural BP-2 mins after standing

– Fall< 10mmHg normal– >30 mmHg abnormal

Investigations• FBS and HbA1c• EMG• Nerve biopsy• ECG• FBC• SEUC• Vitamin B12 and folate levels• ESR,CRP• TFT• ANA• RF• Serum protein electrophoresis• MRI and CT

Staging

• N0-No neuropathy• N1-Signs but no symptoms• N2a-Mild symptomatic,pxt able to heel walk• N2b-Severe symptomatic,pxt unable to heel

walk• N3-disabling diabetic polyneuropathy

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Differential diagnosis

• Herpes Simplex mononeuropathy• Ethanol neuropathy• Vasculitic neuropathy• Amyloid polyneuroathy• Chronic inflammatory demyelinating olyradiculopathy• B12/folate• Malignancy• Myocardial infarction• Renal failure• Drugs• Cord problems• Leprosy• HIV/AIDS

Treatment

• Tight and stable glucose control slows the progression of neuropathy

• Drugs used in peripheral neuropathy include the antidepressants(amitryptiline, desipramine, imipramine, nortriptyline) SSRIs e.g duloxetine anticonvulsants like pregabalin, gabapentin, carbamazepine, lamotrigine

• However response haven’t been satisfactory and patients need lots of psychological support.

Neuropathic treatment ctd

• Other measures include, opiates,mexiletine,Topical capsaicin, lipoic acid, transdermal lidocaine patches

• TENS(transcutaneous electrical nerve stimulation)

• Use of custom shoes for neuropathic foot deformities

• Occupational therapy

Autonomic neuropathy-GITGastroparesis• Improve glycaemic control• Frequent small easier to digest meals• Prokinetic drugs

– Metoclopramide, domperidone, cisapride, erythromycin (250 mg tds)

• Jejunostomy

Diarrhoea• Codeine/loperamide/diphenoxylate• Treat bacterial overgrowth (oxytet/erythromycin) if

suspected/presentConstipation; laxatives e.g senna

Autonomic neuropathy-CVS

• Orthostatic hypotension;

Increase dietary fluid and salt intake

Avoid dehydration

Compression stockings

Fludrocortisone, midodrine, clonidine

Autonomic neuropathy-UGS

• Bladder and voiding problemsIntermittent or permanent self catheterizationProphylactic antibiotics

• ED: phosphodiesterase type 5 inhibitors, apomorphone, intracarvenosal or intraurethral prostaglandins, vacuum devices, or penile prosthesis, psychotherapy

Further measures

• Management and avoidance of other risk factors;Treat hypertension and dyslipidemiaAvoid alcohol and smokingFolate and B12 supplementation

• Follow up;Examine feetUse monofilament and tuning forkGlycaemic assessment (HBA1c)

Counselling for patients with neuropathic foot

• Do check your feet each day for blisters, cuts, scratches, reddened areas. Use a mirror or ask someone else to help look at the soles.

• Do wash your feet each day. Dry them carefully especially between the toes.

• Do avoid extremely hot or cold water. Test them with your hand or elbow before use.

• Do apply a very thin coat of lubricating oil or cream on the skin after bathing if your skin is dry but not between the toes

Counseling ctd

• Do ask about therapeutic shoes if you have a foot deformity, such as bunions or claw toes or previous ulcer

• Do see your care provider for regular foot examination.

• Always protect your feet. Wear shoes both in and outside the house to avoid injury

Counseling ctd• Don’t walk barefoot.• Don’t walk on hot surfaces, such as sandy beaches or the

cement, roads etc.• Don’t put hot water bottles, electric blanket or heating pad on

your feet.• Don't cut corns, calluses or use chemical agents, corn plasters,

strong antiseptics on your feet.• Don’t soak your feet unless professionally advised.• Don’t wear shoes without stockings.• Don’t wear sandals with thongs between the toes.• Avoid pointy-toe shoes, high heels, stilettos, strapless and

backless shoes• Don’t smoke• Don’t put jewellery on your feet

Prognosis

• Repetitive trauma to a neuropathic area may cause ulceration and infection and amputations

• Neuropathic foot ulceration and amputation is the commonest cause of admission of DM patients

• Mortality is mainly from cardiac autonomic neuropathy.

• Such patients are at risk of sudden death

conclusion

• DM neuropathy is the commonest chronic complication in diabetics

• Poor glycaemic control and prolonged duration of DM are the greatest risk factors

• Major cause of non traumatic lower limb amputations as well as sudden deaths

• Strict blood glucose control is advised to prevent or delay it’s progression

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