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Table e-1.Selected International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) Administrative Codes Used to Identify Cases of Polyneuropathy.

ICD-9-CM Code / Description
337.0 / Idiopathic peripheral autonomic neuropathy
337.1 / Peripheral autonomic neuropathy in disorders classified elsewhere
354.5 / Mononeuritis multiplex
356.0 / Hereditary peripheral neuropathy
Déjèrine-Sottas disease
356.1 / Peroneal muscular atrophy
Charcot-Marie-Tooth disease
Neuropathic muscular atrophy
356.2 / Hereditary sensory neuropathy
356.3 / Refsum’s disease
Heredopathia atactica polyneuritiformis
356.4 / Idiopathic progressive polyneuropathy
356.8 / Other specified idiopathic peripheral neuropathy
Supranuclear paralysis
356.9 / Unspecified
357.0 / Acute infective polyneuritis
Guillain-Barre syndrome
Post infectious polyneuritis
357.1 / Polyneuropathy in collagen vascular disease
357.2 / Polyneuropathy in diabetes
357.3 / Polyneuropathy in malignant disease
357.4 / Polyneuropathy in other diseases classified elsewhere
357.5 / Alcoholic polyneuropathy
357.6 / Polyneuropathy due to drugs
357.7 / Polyneuropathy due to other toxic agents
357.8 / Other
357.81 / Chronic inflammatory demyelinating polyneuritis
357.82 / Critical illness polyneuropathy
Acute motor neuropathy
357.89 / Other inflammatory and toxic neuropathy
357.9 / Unspecified

Table e-2.Occurrence of false positive and negative coding for distal Symmetric Polyneuropathy and Ordinal Likelihood of 289 Randomly Selected Neuropathy Coded Cases and 289 No Neuropathy Coded controls per the AAN/AAEM/AAPM&R Guidelines.32

Likelihood of Polyneuropathy / Cases
Coded Neuropathy
No. (%) / Controls
Coded
No Neuropathy No. (%)
++++ / 92 (31.8) / 0 (0)
+++ / 2 (0.7) / 0 (0)
++ / 162 (56.1) / 0 (0)
+ / 14 (4.8) / 15 (5.1)
Total meeting criteria / 270 (93.4) / 15 (5.1)
Documentation did not support a diagnosis of polyneuropathy / 19 (6.6)a. / 274 (94.9)b.
Abbreviation: AAN/AAEM/AAPM&R, American Academy of Neurology/American Association of Electrodiagnostic Medicine/American Academy of Physical Medicine and Rehabilitation.
a. ICD-9 coded polyneuropathy cases (n=19) felt incorrectly or not adequately documented for polyneuropathy: 1) foot pain; 2) right leg pain; 3) polyradiculopathy; 4) fibromyalgia; 5) trophic changes in the feet; 6) thought to have polyneuropathy by family history but no polyneuropathy on exam; 7) thoracic zoster; 8) foot paresthesias after tumor necrosis factor inhibitor drug; 9) Morton's neuroma only documented; 10) normal control in diabetic polyneuropathy study; 11) myasthenia gravis; 12) sensory symptoms secondary to myelopathy; 13) quadriparesis from myelopathy; 14) inclusion body myositis, 15-19) foot symptoms negative studies.
b. Of the 15 no neuropathy controls identified to have polyneuropathy from individual chart review of 289 no neuropathy designated charts the identified types of polyneuropathy found included: 9 diabetic; 1 chemotherapeutic;and 5 idiopathic. Comprehensive neurological examinations sufficient to assess polyneuropathy totaled only 111 of the 289 no neuropathy control charts of which the majority were asymptomatic.

Table e-3. Selected Items from Questionnaires with Assigned mRS Equivalents.

Question / mRS Equivalent
Fill in the circle to the left of each activity that you have difficulty performing on your own.
  • Preparing Meals
/ 3
  • Feeding yourself
/ 4
  • Dressing
/ 4
  • Using the toilet
/ 5
  • Housekeeping
/ 2
  • Bathing
/ 4
  • Walking
/ 4
  • Using transportation
/ 2
  • Getting in and out of bed
/ 5
  • No difficulty with any of these activities
/ 0
Check each symptom that you wish to call to the attention of your healthcare provider:
  • Weakness in arms or legs
/ 3
  • Numbness or shooting pain in hands, arms, legs or feet
/ 1
  • Noticed tendency to fall easily
/ 4
Are you having difficulty with pain?
  • No
/ 0
  • Yes
/ 1
Can you climb two flights of stairs without stopping to rest?
  • Yes, with no difficulty
/ 0
  • Yes, with difficulty
/ 4
  • No, can’t do at all

Do you depend on any assistive devices such as a cane, wheelchair, braces, walker, or assistance from other people to perform activities important to you in your daily life?
  • No
/ 0
  • Yes
/ 4
What is your current employment status?
  • Employed
/ 0
  • Unemployed
/ 0
  • Work disabled
/ 3
  • Student
/ 0
  • Retired
/ 0
  • Self-employed
/ 0
  • Full-time homemaker
/ 0
  • Other
/ 0
Which of the following describes your living environment?
  • House
/ 0
  • Apartment
/ 0
  • Assisted Living
/ 4
  • Nursing Home

  • Other
/ 0

Abbreviation: mRS, Modified-Rankin Scale

Table e-4. Weight of diabetes on Charlson comorbidities among PN cases

Medical Comorbidity / PN with Diabetes
Number (%) / PN without
Diabetes
Number (%) / Total with and without
Diabetes / Prevalence Difference
(P value)
Chronic pulmonary disease / 278 (70.9) / 139 (66.2) / 417 / +4.5% (0.2660)
Peripheral vascular disease / 287 (73.2) / 118 (56.2) / 405 / +17% (<0.0001*)
Cancer
(not solid tumor metastasis) / 229 (75.2) / 158 (58.4) / 387 / +16.8% (<0.0001*)
Renal disease / 286 (73.0) / 97 (46.2) / 383 / +26.8% (<0.0001*)
Cerebrovascular disease / 232(58.8) / 107 (51.4) / 339 / +7.4% (0.3013)
Congestive heart failure / 285(72.3) / 113(54.3) / 398 / +18.0% (<0.0001*)
Mild liver disease / 127 (32.2) / 61 (29.3) / 188 / +2.9% (0.1676)
Myocardial infarct (MI) / 185 (47.2) / 72 (34.3) / 257 / +12.9% (0.0025*)
Peptic ulcer disease / 119(30.2) / 57 (27.4) / 176 / +2.8% (0.8510)
Dementia / 148(37.6) / 87 (41.8) / 235 / -4.2% (0.1621)
Rheumatologic disease / 59 (15.1) / 28(13.3) / 87 / +1.8% (0.6274)
Metastatic solid tumor / 79 (20.2) / 58 (27.6) / 137 / -7.4% (0.0415*)
Hemiplegia / 52 (13.3) / 33 (15.7) / 85 / -2.4% (0.4614)
Moderate or severe liver disease / 35 (8.9) / 23 (10.6) / 58 / -1.7% (0.4691)
AIDS / 0 (0) / 0 (0) / +0%

Table e-5. Accuracy of polyneuropathy classification by ICD-9 coding after individual chart review including those felt not to have polyneuropathy

Polyneuropathy subtype number (N) by ICD-9 coding / With polyneuropathy after chart review / Number without polyneuropathy after chart review
Number (%) with correct subtype by ICD-9 after chart review / Number (%) with incorrect subtype by ICD-9 after chart review
Idiopathic (143) / 104 (81%) / 24 (19%)a / 15
Diabetic (105) / 96 (93%) / 7 (7%) / 2
Inflammatory (17) / 13 (81%) / 3 (19%) / 1
Toxic (10) / 9 (90%) / 1 (10%) / 0
Hereditary (9) / 9 (90%) / 0 (0%) / 0
Other (5) / 4 (100%) / 0 (0%) / 1
  1. The alternative diagnosis felt most accurate among idiopathic polyneuropathy diagnostically miscoded: diabetic N=13 (52%); inflammatory N=3 (12%); toxic N=6 (28%); hereditary N=1 (2%); Other N=1 (2%); No neuropathy N=15.

1

Table e-6. Comparison of Surrogate Markers of Impairment between Idiopathic Polyneuropathy Cases and their Matched Controls Accounting for Comorbidities.

No. (%) with Data / Surrogate Marker of Impairment / Cases
No. (%) / Controls
No. (%) / OR (95% CI) / Adjusted
OR (95% CI)
Cases / Controls
1,449 (100) / 7,200 (100) / Medications / Alpha 2 delta antagonist (gabapentin and pregabalin) / 441 (30.4) / 386 (5.4) / 7.7 (6.6-9.0) / 6.8 (5.9-8.0)
TCA
(amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, and protriptyline) / 253 (17.5) / 257 (3.6) / 5.7 (4.8-6.9) / 5.2 (4.3-6.3)
SNRI
(desvenlafaxine, duloxetine, milnacipran, and venlafaxine) / 158 (10.9) / 202 (2.8) / 4.2 (3.4-5.3) / 4.0 (3.2-5.0)
Topical analgesic
(amitriptyline plus ketamine, capsaicin, and lidocaine) / 170 (11.7) / 254 (3.5) / 3.6 (3.0-4.4) / 3.0 (2.4-3.7)
Opioid analgesic
(codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, and tramadol) / 989 (68.3) / 2,979 (41.4) / 3.0 (2.7-3.4) / 2.6 (2.3-3.0)
Lower limb complications / Lower limb ulcer / 179 (12.4) / 283 (3.9) / 3.4 (2.8-4.2) / 2.5 (2.0-3.1)
Lower limb amputation / 7 (0.5) / 20 (0.3) / 1.7 (0.7-3.9) / 1.0 (0.4-2.3)
Deformity surgery / 42 (2.9) / 121 (1.7) / 1.7 (1.2-2.5) / 1.7 (1.2-2.5)
Ankle fusion / 6 (0.4) / 12 (0.2) / 2.5 (0.9-6.4) / 2.2 (0.7-5.9)
1,052 (73) / 5,006 (70) / Activities of daily living / Preparing meals / 131 (12.5) / 430 (8.6) / 1.5 (1.2-1.9) / 1.1 (0.9-1.4)
Feeding yourself / 23 (2.2) / 88 (1.8) / 1.2 (0.8-2.0) / 0.9 (0.5-1.4)
Dressing / 93 (8.8) / 270 (5.4) / 1.7 (1.3-2.2) / 1.2 (0.9-1.6)
Using the toilet / 57 (5.4) / 162 (3.2) / 1.7 (1.2-2.3) / 1.2 (0.8-1.6)
Housekeeping / 183 (17.4) / 507 (10.1) / 1.9 (1.6-2.2) / 1.4 (1.1-1.7)
Bathing / 111 (10.6) / 347 (6.9) / 1.6 (1.3-2.0) / 1.1 (0.9-1.4)
Walking / 223 (21.2) / 523 (10.4) / 2.3 (1.9-2.7) / 1.8 (1.5-2.1)
Using transportation / 109 (10.4) / 346 (6.9) / 1.6 (1.2-1.9) / 1.2 (0.9-1.4)
Getting in and out of bed / 76 (7.2) / 188 (3.8) / 2.0 (1.5-2.6) / 1.5 (1.1-1.9)
Self-reported impairment / Limb weakness / 202 (19.2) / 371 (7.4) / 3.0 (2.5-3.6) / 2.5 (2.0-3.0)
Limb numbness or shooting pain / 274 (26.0) / 388 (7.8) / 4.2 (3.5-5.0) / 4.2 (3.5-5.0)
Fall tendency / 112 (10.6) / 207 (4.1) / 2.8 (2.2-3.5) / 2.3 (1.8-2.9)
844 (58) / 3,940 (55) / Pain / 380 (45.0) / 1,007 (25.6) / 2.4 (2.0-2.8) / 2.2 (1.9-2.5)
902 (62) / 4,286 (60) / Stair intolerance / 534 (59.2) / 1,617 (37.7) / 2.4 (2.1-2.8) / 1.9 (1.6-2.2)
939 (65) / 4,341 (60) / Assistive device or other assistance / 333 (35.5) / 842 (19.4) / 2.3 (2.0-2.7) / 1.8 (1.5-2.2)
954 (66) / 4,494 (62) / Work-disabled / 39 (4.1) / 60 (1.3) / 3.1 (2.1-4.7) / 2.7 (1.7-4.1)
947 (65) / 4,486 (62) / Assisted living or nursing home / 65 (6.9) / 250 (5.6) / 1.2 (0.9-1.6) / 0.9 (0.6-1.2)

Table e-7.Comparison of surrogate markers of impairment between diabetic polyneuropathy cases and their matched controls accounting for comorbidities.

No. (%) with Data / Surrogate Marker of Impairment / Cases
No. (%) / Controls
No. (%) / OR (95% CI) / Adjusted
OR (95% CI)
Cases / Controls
1,104 (100) / 5,516 (100) / Medications / Alpha 2 delta antagonist (gabapentin and pregabalin) / 379 (65.7) / 333 (6.0) / 8.1 (6.9-9.6) / 5.7 (4.0-8.3)
TCA
(amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, and protriptyline) / 163 (14.8) / 239 (4.3) / 3.8 (3.1-4.7) / 3.5 (2.2-5.7)
SNRI
(desvenlafaxine, duloxetine, milnacipran, and venlafaxine) / 138 (12.5) / 182 (3.3) / 4.2 (3.3-5.3) / 4.9 (2.8-8.8)
Topical analgesic
(amitriptyline plus ketamine, capsaicin, and lidocaine) / 114 (10.3) / 151 (2.7) / 4.1 (3.2-5.3) / 3.5 (2.0-6.4)
Opioid analgesic
(codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, and tramadol) / 775 (70.2) / 2,251 (40.8) / 3.4 (3.0-3.9) / 2.6 (2.1-3.3)
Lower limb complications / Lower limb ulcer / 366 (33.2) / 197 (3.6) / 13.4 (11.1-16.2) / 4.4 (3.1-6.3)
Lower limb amputation / 104 (9.4) / 17 (0.3) / 33.6 (20.6-58.4) / 6.8 (3.1-17.8)
Deformity surgery / 25 (2.3) / 101 (1.8) / 1.2 (0.8-1.9) / 2.5 (1.0-7.1)
Ankle fusion / 7 (0.6) / 15 (0.3) / 2.3 (0.9-5.6) / 2.0 (0.4-17.0)
711 (64.4) / 3,888 (70.5) / Activities off daily living / Preparing meals / 153 (21.5) / 296 (7.6) / 3.3 (2.7-4.1) / 2.3 (1.5-3.5)
Feeding yourself / 22 (3.1) / 67 (1.7) / 1.8 (1.1-2.9) / 1.0 (0.4-2.4)
Dressing / 111 (15.6) / 186 (4.8) / 3.7 (2.9-4.7) / 2.2 (1.4-3.7)
Using the toilet / 64 (9.0) / 119 (3.1) / 3.1 (2.3-4.3) / 1.9 (1.0-3.6)
Housekeeping / 210 (29.5) / 355 (9.1) / 4.2 (3.4-5.1) / 2.2 (1.5-3.2)
Bathing / 133 (18.7) / 240 (6.2) / 3.5 (2.8-4.4) / 1.9 (1.2-2.9)
Walking / 228 (32.1) / 391 (10.1) / 4.2 (3.5-5.1) / 1.9 (1.4-2.8)
Using transportation / 124 (17.4) / 233 (6.0) / 3.3 (2.6-4.2) / 2.3 (1.4-3.7)
Getting in and out of bed / 79 (11.1) / 147 (3.8) / 3.2 (2.4-4.2) / 1.8 (1.1-3.2)
Self-reported impairment / Limb weakness / 127 (17.9) / 275 (7.1) / 2.9 (2.3-3.6) / 1.3 (0.9-1.9)
Limb numbness or shooting pain / 147 (20.7) / 277 (7.1) / 3.4 (2.7-4.2) / 1.9 (1.3-2.8)
Fall tendency / 94 (13.2) / 153 (3.9) / 3.7 (2.8-4.9) / 1.6 (1.0-2.6)
557 (50.5) / 3,063 (55.5) / Pain / 253 (45.4) / 756 (24.7) / 2.5 (2.1-3.1) / 2.0 (1.4-2.8)
615 (55.7) / 3,323 (60.2) / Stair intolerance / 448 (72.8) / 1,204 (36.2) / 4.7 (3.9-5.7) / 1.8 (1.3-2.6)
637 (57.7) / 3,431 (62.2) / Assistive device or other assistance / 339 (53.2) / 639 (18.6) / 5.0 (4.2-5.9) / 2.2 (1.5-3.1)
661 (59.9) / 3,503 (63.5) / Work-disabled / 62 (9.4) / 44 (1.3) / 8.1 (5.5-12.1) / 8.8 (3.4-30.0)
648 (58.7) / 3,468 (62.9) / Assisted living or nursing home / 73 (11.3) / 169 (4.9) / 2.5 (1.8-3.3) / 1.9 (1.1-3.5)