Reviews/Commentaries/Position Statements REVIEW ARTICLE Focal Entrapment Neuropathies in Diabetes 1 1 AARON VINIK, MD, PHD LAWRENCE COLEN, MD millimeters]) is a risk factor (8,9). It used 1 2 ANAHIT MEHRABYAN, MD ANDREW BOULTON, MD to be associated with work-related injury, but now seems to be common in people in sedentary positions and is probably re- lated to the use of keyboards and type- MONONEURITIS AND because the treatment may be surgical (2) writers (dentists are particularly prone) ENTRAPMENT SYNDROMES — (Table 1). (10). As a corollary, recent data (3) in 514 Peripheral neuropathies in diabetes are a patients with CTS suggest that there is a diverse group of syndromes, not all of CARPAL TUNNEL threefold risk of having diabetes com- which are the common distal symmetric SYNDROME — Carpal tunnel syn- pared with a normal control group. If rec- polyneuropathy. The focal and multifocal drome (CTS) is the most common entrap- ognized, the diagnosis can be confirmed neuropathies are confined to the distribu- ment neuropathy encountered in diabetic by electrophysiological studies. Therapy tion of single or multiple peripheral patients and occurs as a result of median is simple, with diuretics, splints, local ste- nerves and their involvement is referred nerve compression under the transverse roids, and rest or ultimately surgical re- to as mononeuropathy or mononeuritis carpal ligament. It occurs thrice as fre- lease (11). The unaware physician seldom multiplex. quently in a diabetic population com- realizes that symptoms may spread to the Mononeuropathies are due to vasculitis pared with a normal healthy population whole hand or arm in CTS, and the signs and subsequent ischemia or infarction of (3,4). The increased prevalence in diabe- may extend beyond those subserved by nerves (1). Common mononeuropathies tes may be related to repeated undetected the nerve entrapped. Motor weakness is involve cranial nerves III, IV, VI, and VII trauma, metabolic changes, accumulation uncommon, but thenar muscle wasting and thoracic and peripheral nerves, in- of fluid or edema within the confined particularly occurs in the elderly. Tinel cluding peroneal, sural, sciatic, femoral, space of the carpal tunnel, and diabetic sign for median nerve percussion at the ulnar, and median. Their onset is acute, cheiroarthropathy (5), rheumatoid arthri- wrist is positive in 61%, and Phalen’s test associated with pain, and their course is tis, and hypothyroidism (1,3). CTS is wrist flexion is only 46% positive, with a self-limiting, resolving over a period of 6 found in up to one-third of patients with high false-positive rate. Quantitative sen- weeks. They must be distinguished from diabetes, when demonstrated electro- sory tests for the different sensory modal- entrapment syndromes that start slowly, physiologically, but may only be symp- ities, including pain, temperature, and progress, and persist without interven- tomatic in ϳ5.8% (6). It is more common spatial orientation, are notoriously unre- tion (Fig. 1). Common entrapments in- in females and in obese individuals (BMI liable (4). Thus, the very nature of the volve the median, ulnar, and peroneal Ͼ30 kg/m2) and affects the dominant trouble goes unrecognized, and an oppor- nerves, the lateral cutaneous of the thigh, hand (7). It occurs in 2% of the general tunity for successful therapeutic interven- and the tibial nerve in the tarsal canal. The population, 14% of diabetic subjects tion is often missed. Electrophysiological entrapment neuropathies are highly prev- without diabetic polyneuropathy, and studies measure the speed of conduction alent in the diabetic population, one in 30% of diabetic subjects with diabetic across the carpal tunnel, and median sen- every three patients has one, and it should polyneuropathy. It peaks at around sory nerve conduction studies are com- be actively sought in every patient with 40–60 years of age and an increased pared with radial and/or ulnar sensory the signs and symptoms of neuropathy “wrist index” (wrist depth/wrist width [in latencies. Their interpretation is made dif- ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● ficult if there is a coexisting peripheral From 1The Diabetes Institute, Eastern Virginia Medical School, Norfolk, Virginia; and the 2Manchester Royal neuropathy affecting the upper limbs or if Infirmary, Oxford, U.K. there are no symptoms of CTS. Demyeli- Address correspondence and reprint requests to Aaron Vinik, MD, The Diabetes Institute, Eastern Virginia nation is thought to be the primary patho- Medical School, 855 W. Brambleton Ave., Norfolk, VA 23510. E-mail: [email protected]. logical abnormality. Electromyography Received for publication 2 February 2004 and accepted in revised form 11 April 2004. A.V. has received consultant’s fees from or served on the speaker’s bureaus for Pfizer, Genetech, Merck, activity can be particularly useful in dis- Eli Lilly, Athena, Bristol Meyers Squibb, Knoll Pharmaceuticals, GlaxoSmithKline Beecham, Boston Medical tinguishing this from distal symmetric Technologies, Neurometrix, Guilford Pharmaceuticals, R.W. Johnson Pharmaceutical Research Institute, polyneuropathy (DSPN) and the double- Takeda, TEVA Pharmaceutical Industries, AstraZeneca, Synergy Biosciences, Amgen, Forest Laboratories, crush syndrome of C7–8 radiculopathy Sigma Tau Research, and Sankyo; and has received grant support from GMP-Endotherapeutics, the Amer- (12). The high sensitivity and specificity ican Diabetes Association, the U.S. Department of Housing and Urban Development, the National Aeronau- tics and Space Administration, Eli Lilly, AstaMedica, the National Institute on Aging, R.W. Johnson, the of nerve conduction studies make them National Institutes of Health, the Juvenile Diabetes Foundation International, Takeda America, the Depart- the most valuable diagnostic method for ment of Health and Human Services Public Health Services, and PPD Development. CTS (80% sensitive). Wrist-palm stimu- Abbreviations: CTS, carpal tunnel syndrome; DSPN, distal symmetric polyneuropathy; NCV, nerve lation is the most sensitive technique conduction velocity; PSSD, pressure-specified sensory device; TTS, tarsal tunnel syndrome. A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion (61% sensitivity in diagnosis of CTS). factors for many substances. Moreover, it is the only technique to di- © 2004 by the American Diabetes Association. agnose subclinical cases and differentiate DIABETES CARE, VOLUME 27, NUMBER 7, JULY 2004 1783 Focal entrapment neuropathies in diabetes Table 1—Clinical features of entrapment syndromes: location, impairments, and diagnosis Location of the most Distribution common of sensory Distribution of Diagnosis by Differential Nerves entrapments impairment motor impairment Signs NCV diagnosis Median nerve Wrist (CTS) Palmar aspects of Weakness and at- Tinel’s sign, Phalen’s Wrist/palm stim- C8 radiculopathy, I–III, 0.5 IV fin- rophy of abduc- maneuver, carpal ulation proximal com- gers, medial as- tor policis brevis compression test, pressions of me- pect of the palm, and weakness of dian nerve and intact thenar thumb opposition eminence Ulnar nerve Elbow (cubital Palmar aspects of V, Weakness and atro- Tapping or pressure Below/above elbow C8-T1 radiculopathy, tunnel syn- 0.5 IV fingers, phy of adductor over the ulnar stimulation brachial plexoapthy drome) medio-dorsal as- digiti minimi, nerve at the medial (medial cord), and pect of the hand, hypothenar, and epicondyle repro- ulnar nerve entrap- and hypothenar intrinsic muscle of duces sensory ment at the wrist eminence the hand symptoms, Fro- ment’s sign Radial nerve Elbow (radial Dorsal aspect of the Drop wrist: weak- Aching and soreness NCV–electromyo- Wartenberg’s syn- groove) forearm, hand, ness of the exten- in the elbow re- graphy activity* drome, tennis and fingers I–III sors of the hand gion, weakness of elbow, radiculopa- and 0.5 IV and fingers, intact supination and thy C7, brachial function of the extension of index plexopathy (poste- forearm extensors finger and hand rior cord) Peroneal nerve Fibula head Lateral aspect of the Drop foot: weakness Tapping or pressure Above/below fibula Compression at the leg and dorsum of of the extensors of below the fibula stimulation knee level, radicu- the foot foot and toes head provokes sen- lopathy L5 sory symptoms Tibial nerve Ankle-tarsal Plantar: medial and Atrophy of the in- Tinel’s sign, tapping Sensory medial and Radiculopathy S1, tunnel lateral surfaces trinsic muscles in the nerve distri- lateral plantar polyneuropathy of the foot bution nerves (DSPN), and Morton’s neuroma Lateral cutaneous Ilioinguinal liga- Lateral aspect of None Extremely sensitive Above/below ilio- Femoral neuropathy, nerve of the ment (meralgia the thigh skin in correspond- inguinal liga- radiculopathy thigh paresthetica) ing dermatome ment stimulation L2–3, and lumbar plexopathy *Radial nerve entrapment requires conduction velocity done over muscles of forearm because, unlike the ulnary median nerves, the radial nerve does not innervate muscles in the hand. entrapment from DSPN. Combined en- ness, and failure of nonsurgical treatment. 25 nondiabetic patients. Global symptom trapment of median and ulnar nerves can Of particular note is the very elegant scores as well as electrophysiological evi- mimic DSPN and can only be distin- study by Ozkul et al. (13). They com- dence of recovery of nerve function were guished by nerve conduction velocity pared the outcome of carpal tunnel re- evaluated at 1 month