Diagnosis and Management of Diabetic Neuropathies

Part 3

Aaron I. Vinik, MD, PhD, FCP, MACP Professor of Medicine/Pathology/NeurobiologyDirector of Research and Neuroendocrine Unit

Eastern Virginia Medical SchoolStrelitz Diabetes Center for

Endocrine and Metabolic DisordersNorfolk, Virginia

Clinical Examination Inspection (May Be Normal)

Insensate foot:repeated minor trauma causes ulceration

Autonomic features• Dry skin, hairless• Distended veins• Edema• Cold (hot if Charcot’s)

Assessment of FootwearInappropriate Footwear Is the Commonest Form of Trauma

Simple Bedside Tests of Large-Fiber Function

Controls (n=11)

Diabetic controls (n=8)

Diabetic neuropathy (n=14)

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2-minutewalk

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Tandemstand

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Balance walk

Foot tapping

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Resnick et al. Muscle Nerve. 2002;25:43. * P<0.05 vs nondiabetic controls; †P<0.01 vs nondiabetic controls

Sensory NervesMonofilament Testing at Dorsum of Great Toe

3.8 Monofilament• Light touch, 1.0 g force• Record if felt ¾ touches (y/n)

5.01 Monofilament • Standard, 10 g force• Only performed if “no”

for 1.0 g• Record if felt ¾ touches (y/n)

25 lb strain fishing line4 cm = 10 g8 cm = 1 g

Bourcier et al. J Fam Pract. 2006;55:505.

Shy ME et al. Neurology. 2003;60:898.Rolke R et al. Eur J Pain. 2006;10:77.

Quantitative Sensory Testing

Determines threshold for• Vibration─large fiber• Thermal (warm and cold)─small fiber• Hot and cold pain• Touch─pressure• CHEPS─allows recognition of sites• Electrical impulses

Strengths• Measures both small- and large-fiber deficit• Relatively simple, less discomfort• Useful tool for screening large populations

Limitations• Less objective (psychophysical)• Less reproducible• No standardization of various systems

(reliant on normative values for each lab)

Vibration Perception Threshold

• Detects subclinical DSP

• Predicts foot ulceration1,2

0–15 V ─ Low risk16–25 V ─ Intermediate25 V ─ High risk

(7)

• Predicts mortality3

BiothesiometerNeuroasthesiometerVibrameterVibratron CASE IVMedoc etc.

1. Young MJ et al. Diabetes Care. 1994;17:557.2. Abbott CA et al. Diabetes Care. 1998;21:1071.

3. Coppini DV et al. Diabetic Med. 2000;17:488.

Nerve-Conduction StudiesAbility of Nerves and Muscle to React to

Electrical Stimulation

Strengths• Most objective, accurate, reproducible,

sensitive• Correlate with clinical end points• Represent pathologic hallmark of DSP• Diagnostic sensitivity improved by

incorporation of anthropometric factors, F-wave testing, etc.

Limitations• Measure only large-fiber function• Limited availability for routine testing• Some discomfort• Impact of external factors

(eg, limb temperature, etc.) Daube JR. Muscle Nerve. 1999;22:1151. Malik RA et al. Diabetologia. 1989;32:92.

Perkins BA et al. Diabetes Care. 2001;24:748.

Quantitative Measurement of Cutaneous Perception in

Diabetic NeuropathySensitivity with specificity >90%

Warm 78%

Cold 77%

VDT 88%

Tactile 77%

CPT <50%

Combination thermal (CDT) and VDT

Sensitivity 92%–95%

Specificity 77%–86%

0 50 100Specificity (%)

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0Two-point discCPT 2000 HzCPT 250 HzCPT 5 HzPressureColdWarmVibration

Vinik AI et al. Muscle Nerve. 1995;18:574.CDT, cooling detection threshold; CPT, current perception testing; VDT, vibration detection threshold

CHEPSContact Heat-Evoked Potential Stimulator

• Objective and noninvasive • Selective stimulation and identification of A and C fibers

through EEG signal waveform recording1,2 • Quantifies negative and positive latencies, amplitudes, and

conduction velocities3

– Neuropathic patients demonstrate reduced amplitude and prolonged latencies

Medoc, NC1. Chao CC et al. Clin Neurophsyiol. 2008;119:653.

2. Staud R et al. Pain. 2008;139:315.3. Granovsky Y et al. Pain. 2005;115:238.

CHEPS Response Selective A and C-Fiber Activation

C fibers• Thin, unmyelinated fibers, conduction velocity <2 m/sA fibers• Thin, myelinated fibers, conduction velocity 10–30 m/s • Receptors located mainly on hairy skin• Conduct sensation about first, sharp, pricking pain• Activated by temperature <45°C and mechanical stimuli• Two main groups of A mechano-heat (AMH) nociceptors

– Type I AMH, threshold >50°C– Type II AMH, heat threshold <50°C

EEG response toselective C-fiber stimulation

EEG response toselective A fiber stimulation