Diabetic peripheral neuropathy

  • most common causes

  • up to 50% of people with DM

    • over half asymptomtic or numbness only symptom

  • reported symptoms

    • sensory disturbance

    • autonomoic dysfunction

    • weakness

  • 90% symmetrical distal polyneuropathy

    • multiple nerves involved

    • occurs in combination with autonomic neuropathy

  • mononeuropathies happen less often

  • may have more than one type

  • many mechanisms involved

    • increased oxidative stress

    • build-up of glycation ednd produces

    • increased activity of polyol pathway

    • activation of proinflammatory mechanisms

    • ischaemia

    • all have effects of neurons/Schwann cells + vascular tissue that supply nerves

  • All nerves (sensory, autonomic, motor, myelinated&unmyelinated) affected

  • risk of developing neuropathy proportional to both magnitude and duration of hyperglycaemia

  • other modifiable risk factors

    • smoking

    • hypertension

    • obesity

    • dyslipidaemia

  • consider other causes:

    • medicines

    • systemic conditions

    • infections

    • autoimmune disorders

    • toxins

    • trauam

    • inherited conditions

  • neuropathy more likely to happen in dm due to:

    • b12 def

    • uraemia

    • hypothyroidism

    • chronic inflammatory demyelinating polyneuropathy (CIDP) (may)

  • therefore DM neuropathy likely diagnosis of exclusion

  • “diabetic foot” = most feared outcome

    • loss of protective sensation

    • + associated reduced perfusion from arterial disease

    • increase risk of ulceration, infection, amputation

  • adverse outcome on sleep, mood, ADL, independence, mood

  • increase risk of falls and fracture

  • risk of amputation = 1.7x increase to 12x if deformity of foot and 36x if previous history of ulceration

    • half foot ulcers could be prevented

classification

Symmetric distal polyneuropathy

  • +/- autonomic neuropathy

    • may affect both sympathetic and parasympathetic functions +/- sensorimotor neuropathy

    • cardiovascular

      • resting tachycardia

      • orthostatic hypotension

      • exercise intolerance

      • silent myocardial ischaemia

    • gastrointestinal

      • symptoms of gastroparesis

        • satiety

        • bloating

        • vomiting

        • erratic glucose control following meals

      • diarrhoea

      • constipation

      • faecal incontinence

    • genitourinary

      • bladder-voiding (neurogenic bladder)

      • erectile dysfunction

        • enquire about ED at least once/year

      • retrograde ejaculation

      • female sexual dysfunction

    • sudomotor (sweat)

      • heat intolerance

      • excessive sweating upper/red. lower

      • sweating after meals

    • metabolic

      • hypoglycaemia unawareness

      • hypoglycaemic associated autonomic failure

    • ocular

      • pupillomotor function impairment

      • Argyll-Robertson pupil

        • small pupil that constrict poorly to light but rapidly to close object

      if peripheral neuropathy mild but strong autonomic features consider alternate diagnosis; amyloid neuropathy

  • most common type

  • symptoms:

    • vary

    • loss of pain sensation and ability to perceive changes in temperature tend to resutl of damage to Type C - small sensory

    • loss of touch, vibration, proprioception and motor innervation - large fibres = Type A

    • classified:

      • positive: pain

        • burning or knifelike pain

        • electrical sensations

        • squeezing

        • constricting

        • freezing

        • throbbing

        • allodynia

          • pain provoked by stimulus not normally painful

        • from increased uninhibited sensory firing from damaged nerve fibres

      • negative: non-painful

        • tingling

        • swelling

        • prickling

        • numbness

        • walking on “cotton wool”

        • limb asleep or dead

        • from reduced signalling from damaged nerves

    • usually start toes and progress proximally in stocking distribution - feet and legs

    • longest axons affected first

      • “length dependent”

    • fingers -> up arm (uncommon unless symptoms in legs have progressed to mid-thigh level

    • generally symettrical

    • typically nocturnal exacerbations

Hyperglycaemic neuropathy

  • acute sensory neuropahty

  • symmetrical polyneuropathy (acute/subacute)

  • severe sensory symptoms

    • pain

    • parathesia

    • numbness

  • rare

  • usually occurs folloowing episode of glycaemic instability

  • relatively normal physical examination

    • loss of light touch sensation

    • allodynia may be present on sensory testing

    • occ. ankle relexes will be reduced

    • motor = normal

Acute painful sensory neuropahty

  • insulin neuritis

Focal/multifocal

  • cranial neuropathy

    • 6th nerve palsy

    • 3rd neruve

    • full recovery usually within 3-6mo

  • focal limb neuropathy

    • secondary to compression/entrapment

  • throacolumbar radiculoneuropathy

    • unilateral pain and hyperaesthesiae

      • focal area on chest/abdomen with abrupt onset

      • spont. recovery over a few months

      • t1 + t2

  • lumbosacral radiculoplexus neuropathy

    • motor nerves of prox. muscles of legs

    • T2DM, M, older

    • severe aching or burning pain that affects lower back, buttocks and thighs

    • often worse at night

Examination

  • inspection:

    • feet

      • skin

        • erythematous areas

        • dryness

          • may be due to autonomic dysfucntion

        • flakiness

        • thickness

        • cracking

        • callus formation

          • localised rubbing/friction

        • infection

        • ulceration

    • patient’s footwear

  • musculoskeletal assessment for deformity

    • prominence of metatarsal heads

      • increase risk of skin breakdown

    • callus

      • most common formed on plantar surgace beneath first metatarsal head due to focal pressure during walking

    • hyperextension of MTPJ with flexion of interphalangeal joints

      • claw toes

    • extension at DIPJ == hammer toes

    • charcot arthorpathy

      • neuropathic arthropathy

      • 10% of people with neuropathy

      • colllapse of midfoot

        • tarso-metatarsal joint

        • “rocker bottom”

    • motor = muscle atrophy

      • “gettering” between metatarsals and muscle weakness - weakness of toe dorsiflexion followed by weakness of foot dorsiflexion

  • neurological assessment

    • pattern = symmetrical distal polyneuropathy

    • non dermatomal

    • affecting all modalities

    • sensory loss most often determined use of monofilament testing

      • 10g monofilament

      • 12 sites - 6 each foot

        • Great toe

        • overs 1st MT base

        • 2/3 MT base

        • little toe

        • 5th MT base

        • heel

      • avoid areas of callus

      • pressed slowly over 3 seconds

    • vibration = 128Hz

      • first objective evidence of symmetric dital polyneuropathy

    • deep tendon relexes may be reduced - especially at ankle

  • vascular assessment of feet and assessment of HR and BP (lying/sitting and standing)

    • peripheral artery disease = important risk factor for development of ulceration

      • 1/3 of foot ulcers

    • pulses palpated

    • ABPI

      • can be falsely elevated in DM

Management

  • aim:

    • reduction of patients symptoms to tolerable level

    • prevention of further damage

  • no speicifc treatment

  • good glycaemic control amy stabilise or improve peripheral neuropathy over time

  • symptoms control

    • Mild

      • paracetamol/NSAID

    • TCA/anticonvulsant

    • add opiod if not controlled

  • Exercise

    • combining stregngth and aerobic activities

      • reduces pain

      • improving function

        • increase plantar sensation

        • increase ability to detect vibrations

        • improve trunk and ankle proprioception

    • involve glial cell activation and release of noradrenaline and cytokines

    • other benefits

      • enhanced macro and micro vascular health

      • reduced risk of hypertension

      • atherosclerosis

      • increase muscle strength

      • reduced glycaemic levels

  • protect insensate feet from trauma

    • avoid ulcers

  • refer to community podiatrist = intermediate to high risk of foot complications

Refer

  • pronounced asymmetry of neurologic deficits

  • Predominant motor deficits, mononeuropathy, cranial nerve involvement

  • rapdi developement or progression of neuropathic impairment

  • progression of neuropathy despite optimal glycaemic control

  • symptoms arising in upper limbs

  • proximal weakness

  • significant sensory ataxia

  • FHx of non-diabetic neuropathy

  • Pain difficult to manage

differntial diagnosis

  • Acquired

    • Traumatic

      • common cause

      • partially, completely severed, crushed, compressed or stretched

    • Autoimmune and infectious neuropathy

      • Guillain-Barre

      • CIDP

        • over represented in people with DM

        • prox or both prox and distal weakness

        • early or marked upper limb involvement

        • severe sensory ataxia

        • continued rapid progression despite reasonable glycaemic control

        • Refer

          • electrodiagnosis

          • CSF proteins

      • Infective - tend to be asymetric

    • Systemic causes

      • liver disease

      • etoh

      • renal failure

      • nutrient deficiency

        • vit b12

          • metformin reduces absorption

      • papaproteinaemic disorders

      • thyroid dysfunction

    • Other

      • medicines

        • metronidazole

        • nitrofurantoin

        • amiodarone

        • cochicine

        • phenytoin

  • Inherited

    • Charcot-Marie-Tooth

      • family history

      • insidious onset

      • gradual progression

      • lack of sensory symptoms despite signs

      • pes cavus