Beruflich Dokumente
Kultur Dokumente
Polyneuropathies
Michelle L. Mauermann, M.D.,1 and Ted M. Burns, M.D.2
ABSTRACT
P eripheral neuropathy has an estimated preva- (3) characterization of the neuropathy, and (4) execution
lence of 2 to 3% in the general population and a of a focused workup based on that characterization.5
prevalence as high as 8% in people older than 55 years.1,2 Step 3, the characterization of the neuropathy, is a
Evaluation for the cause is important because diagnosis critical, yet often overlooked step that when performed
of an underlying etiology may allow treatment that allows the clinician to engage in an appropriately focused
prevents progression to disability and poor quality of evaluation. We present our easy-to-remember method
life.3 However, the evaluating physician is faced with the for characterizing neuropathy, based on answering four
knowledge that there are more than 100 potential clinical questions about the neuropathy and the patient:
etiologies of polyneuropathy, yet approximately one ‘‘What?,’’ ‘‘Where?,’’ ‘‘When?,’’ and ‘‘What setting?’’
third of cases will remain idiopathic despite appropriate (Fig. 1).5 The usefulness of this characterization is
testing.1,3,4 This can contribute to uncertainty about the illustrated throughout this article. Electrodiagnostic
level of aggressiveness and the direction of the evalua- testing can be helpful in providing additional insight
tion. This sometimes leads to a ‘‘one size fits all’’ strategy, into the characterization of the neuropathy.
a strategy that is unfocused, inefficient, and costly, and
that sometimes places the patient at unnecessary risk of a
procedure-related complication (e.g., nerve biopsy, lum- WHAT?
bar puncture). The question ‘‘What?’’ refers to which nerve fiber modal-
The fundamental steps for evaluating patients ities (motor, sensory, autonomic, or a combination) are
with neuropathy are: (1) collection of clinical data involved. At a minimum, the identification of sensory
(history of present illness, detailed family history, exami- nerve involvement allows the clinician to exclude other
nation, etc), (2) determination of what data are relevant neuromuscular diseases not associated with sensory dys-
and what are not (to do this well requires, among other function, such as myopathies, neuromuscular transmis-
things, an understanding of risk factors for neuropathy), sion disorders or disease of the anterior horn cell (e.g.,
1
Department of Neurology, Mayo Clinic, Rochester, Minnesota; @mayo.edu).
2
Department of Neurology, University of Virginia, Charlottesville, Neuromuscular Disorders; Guest Editor, Ted M. Burns, M.D.
Virginia. Semin Neurol 2008;28:133–151. Copyright # 2008 by Thieme
Address for correspondence and reprint requests: Michelle L. Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001,
Mauermann, M.D., Department of Neurology, Mayo Clinic, 200 First USA. Tel: +1(212) 584-4662.
Street SW, Rochester, MN 55902 (e-mail: mauermann.michelle DOI 10.1055/s-2008-1062270. ISSN 0271-8235.
133
134 SEMINARS IN NEUROLOGY/VOLUME 28, NUMBER 2 2008
amyotrophic lateral sclerosis). When sensory symptoms (allodynia) or may report increased sensitivity to painful
and signs are present, the characterization of neuropathic stimuli (hyperalgesia). Most patients with neuropathy
sensory symptoms as being ‘‘positive’’ or ‘‘negative’’ acts as have some degree of motor nerve involvement (on
a diagnostic watershed (Fig. 1) because acquired neuro- examination or based on electrodiagnostic testing)
pathies are usually accompanied by positive neuropathic that is often overshadowed by their sensory complaints,
sensory symptoms and inherited neuropathies are usually although motor nerve or fiber symptoms are infre-
not accompanied by positive neuropathic sensory symp- quently the sole complaint. If the abnormalities are a
toms (although patients with inherited neuropathies dis- combination of motor and sensory involvement, it is
play signs of sensory nerve involvement with negative sometimes helpful for the clinician to rank them in
neuropathic sensory symptoms, such as sensory loss and order of symptom predominance (e.g., inflammatory
sensory ataxia).6 For example, in one cohort of more demyelinating neuropathies often manifest with weak-
than 60 patients with autosomal dominant inherited ness overshadowing sensory nerve fiber disturbance).
Charcot-Marie-Tooth (CMT) disease 1A, only two sub- Establishment of autonomic nerve involvement can be
jects complained of positive neuropathic sensory symp- an important clue because the number of processes
toms.7 In contrast, 90% of patients with Guillain-Barré that affect both autonomic and somatic nerves is relati-
syndrome (GBS), chronic inflammatory demyelinating vely few (Table 1).1,4,12 Autonomic symptoms include
polyradiculoneuropathy (CIDP), and alcoholic neuropa- lightheadedness, syncope, diarrhea, constipation, post-
thy note positive neuropathic sensory symptoms.8–11 Pos- prandial bloating, early satiety, urinary complaints,
itive neuropathic sensory symptoms may be painful erectile dysfunction, abnormal or absent sweating, and
(electric shock, burning, freezing, tightness and throb- dry mouth and eyes. Gastrointestinal dysmotility
bing) or painless (tingling, swelling, and bunched-up manifesting as constipation or postprandial bloating is
socks). Patients may also complain of discomfort or a particularly common accompaniment of paraneoplastic
pain to sensory stimuli that are normally not painful neuropathy.13–15 Autonomic nervous system involve-
EVALUATION OF CHRONIC AXONAL POLYNEUROPATHIES/MAUERMANN, BURNS 135
further investigation and identification of a specific Once the physician has achieved familiarity with
inherited neuropathy.25 the patient’s unique clinical setting, he or she must
Second in importance to a detailed family history consider whether the rest of the neuropathy character-
in defining the clinical setting may be obtaining a izations (the what, where, and when?) fit with the
detailed history of alcohol intake, particularly if the clinical setting, and also must consider other possible
physician encounters vague responses to questioning etiologies before implicating a disease or other risk factor
about alcohol intake. In many instances it is illuminating as the cause of the neuropathy. For example, the co-
to probe more into an alcohol consumption history, but morbidity of DM in a patient with neuropathy does not
this must be done in a manner that the patient finds to be prove diabetes is causative, as it is posited that 2% of type
nonjudgmental and nonthreatening. 1 diabetics and 6% of type 2 diabetics have causes other
Past medical and medication histories are obvi- than diabetes for their neuropathy.26
ously also very important considerations for elaborating While this algorithm (Fig. 1) works for the vast
the patient’s unique clinical setting. Diabetes mellitus majority of neuropathy presentations there are excep-
(DM), end-stage renal disease, vitamin deficiency, HIV, tions. Some notable exceptions are: distal symmetric
and paraproteinemia are just some of the disorders that presentation of neuropathies associated with systemic
are risk factors for development of neuropathy. Toxic lupus erythematosus, Sjogren’s syndrome and parapro-
neuropathy caused by medication is uncommon other teinemia, positive neuropathic sensory symptoms in fam-
onset, but it is unusual for a patient to report a more dL ( 11.1 mmol/L) during an oral glucose tolerance
definite date of onset. Progression is gradual over test (OGTT) on two occasions on different days is
months to years. necessary to diagnose DM. HgA1c helps to demonstrate
What setting? No family history of neuropathy, glycemic control over the previous 3 months but should
no foot deformities, onset in adulthood; consider co- not be used for diagnosis. Hence, there is little reason for
morbidities (e.g., prior medical history of diabetes) or a neurologist to be checking HbA1c levels unless he or
risk factors for development of them (e.g., family history she is also managing a patient’s DM. In DPN, the most
of diabetes). common electrodiagnostic test abnormality is reduced
lower extremity sensory nerve action potential amplitudes
(SNAPs). Motor responses can be normal, but often
Diabetes Mellitus show mild abnormalities. A purely small-fiber neuro-
pathy will have normal electrodiagnostic test results.37,38
ASSOCIATION WITH NEUROPATHY
Diabetes mellitus is common and it commonly causes IMPAIRED GLUCOSE METABOLISM AND NEUROPATHY
neuropathy. The prevalence of diagnosed DM is 5% for The 2003 American Diabetic Association (ADA) guide-
U.S. adults older than 20 years of age and 20% for U.S. lines defined impaired fasting glucose (IFG) as a plasma
adults older than 60 years.32,33 Neuropathy affects 50% glucose level greater than > 100 and < 126 mg/dL and
velocity, peroneal nerve velocity, and electromyographic duction velocities, and low or absent compound muscle
change.42 There was also a trend toward a shorter action potential (CMAP) and SNAP amplitudes.50
duration of symptoms.
In apparent conflict with these retrospective re-
ports is one prospective trial by Hughes and colleagues46 Thiamine Deficiency
that compared 50 patients with CIAP with 50 control
individuals. The study found 32% of patients and 14% of ASSOCIATION WITH NEUROPATHY
controls had impaired glucose tolerance or fasting hyper- Thiamine (vitamin B1) deficiency is seen most com-
glycemia. However, when these results were adjusted for monly in chronic alcohol abuse, recurrent vomiting, total
age and gender, the difference was not significant for parenteral nutrition, and following weight reduction
either the entire cohort or the painful symptoms sub- surgery (bariatric surgery).53 Deficiency also can occur
group. These authors instead found a significant associ- in individuals with chronic gastrointestinal problems or
ation with hypertriglyceridemia. These conflicting those who are elderly, on cancer treatment, or those who
results suggest further studies may be needed before are receiving diuretic therapy. Severe deficiency causes
concluding an association. congestive heart failure (wet beriberi), peripheral neuro-
In evaluation of impaired glucose metabolism, pathy (e.g., dry beriberi), Wernicke’s encephalopathy,
many authors suggest that the 2-hour OGTT is a more and Korsakoff’s syndrome. Symptoms and signs of mild
stores.55 Transketolase (TK) assay, once considered the taneously in the hands and feet, is not uncommon in
preferred test to determine thiamine status, is now cobalamin-deficient neuropathy þ / myelopathy. Also,
considered inferior because of low sensitivity and spe- symptom onset may be sudden with a definite date.
cificity. Electrodiagnostic testing shows reduction in Thus, cobalamin-deficiency neuropathy often presents
CMAP and SNAP amplitudes with predominant differently than do other metabolic neuropathies. Pain is
large-fiber loss.11 also less likely to occur.60 Myelopathy is frequent in
cobalamin-deficiency, sometimes serving as a clue to
diagnosis, and it may be difficult to determine whether
Hypothyroid the sensory symptoms are caused by myelopathy or
neuropathy.
ASSOCIATION WITH NEUROPATHY Workup of cobalamin deficiency should include a
Hypothyroidism is common with an incidence of 3.5 serum B12 level. It has been suggested with cobalamin
cases per 1000 women per year and of 0.6 cases per 1000 levels in the low-normal range (but less than 300 pg/mL),
men per year.56 In one study of newly diagnosed that testing of serum homocysteine and methylmalonic
patients, 42% had clinical symptoms and signs of distal, acid will demonstrate cobalamin deficiency in 5 to 10%;
symmetrical, sensory-predominant neuropathy with de- and in 0.1 to 1% of those with a serum cobalamin level
creased ankle reflexes; however, only 17% were con- of greater than 300 pg/mL.60 In cobalamin-deficient
length-dependent, sensory, predominant axonal neuro- of patients had electrophysiological evidence of poly-
pathy.61 However, except for neuropathy caused by neuropathy and one fourth had autonomic neuropathy.67
alcohol, toxic neuropathies are probably overinvesti- The direct toxic effect of alcohol on peripheral nerves
gated and overdiagnosed3; in fact, they probably repre- seems to be the most important etiology.68 Other
sent well below 5% of cases of chronic distal, investigators prospectively identified neuropathy in
symmetrical, sensory, or sensorimotor neuropathies.62 58% of alcoholics, which correlated with the age of the
Nonetheless, prompt identification of a toxic neuro- patient and the duration of alcohol use.68
pathy is important because removal of any harmful
agent may lead to improvement or resolution of neuro- NEUROPATHY
pathy. The list of potentially offending agents that we Alcoholic neuropathy is distal, symmetrical, sensory
provide in Table 2 is long and includes many common predominant, and slowly progressive. There are positive
medications and agents that the population is frequently neuropathic sensory symptoms of pain and/or burning
exposed to in low doses. The relative risk estimate of the and loss of superficial sensation, particularly nociception,
drug causing neuropathy must be considered in the on examination.10,11,67 In one study, the neuropathy was
context of the overall prevalence of neuropathy in pure sensory (47%) or sensory-predominant sensorimo-
the general population, the likelihood the neuropathy tor (53%).11
has an alternative cause, temporal association of drug With respect to laboratory features, in one series,
concentration.84 Cerebrospinal fluid (CSF) Lyme poly- ment or enhancement of affected nerves.93 Electrodiag-
merase chain reaction (PCR) has 40 to 50% sensitivity nostic testing usually reveals an asymmetrical, multifocal
and 97% specificity.81 axonal process.93,95
glandular inflammation (e.g., parotid), as sometimes fibers with increased axonal degeneration.128 The elec-
dry eyes and mouth may be a manifestation of con- trodiagnostic test results for patients with painful
current autonomic ganglionopathy (e.g., inflammation sensory neuropathy without ataxia is in keeping with
damaging the otic ganglion) or a side effect of a a predominantly small-fiber neuropathy (e.g., normal
medication rather than of glandular inflammation. It results).128
has recently been proposed that these neuropathies
instead be classified as immune-sensory and autonomic
neuropathies with or without sicca.131 Systemic Lupus Erythematosus
The neuropathy of SS is secondary to vasculitis in
some cases and secondary to mononuclear cell infiltra- ASSOCIATION WITH NEUROPATHY
tion without vasculitis (e.g., ganglionitis) in other cases. The incidence of SLE is 124 cases per 100,000 people
There also may be other mechanisms of neuropathy; for and affects women much more than men.134 It is more
example, the etiology of the small-fiber neuropathy seen prevalent among Asians, African Americans, and Native
in some cases of SS may be different. Several patterns of Americans in the United States. SLE is associated with
neuropathy are seen in association with SS: sensory variable combinations of fever, rash, alopecia, arthritis,
ataxic neuropathy, painful sensory neuropathy without pleuritis, pericarditis, nephritis, anemia, leukopenia,
ataxia, multiple mononeuropathies, multiple cranial thrombocytopenia, and nervous system disease. Neuro-
the most common class of paraprotein associated with present. Autonomic involvement occurs in the majority
MGUS in the general population; however, IgM with a of patients and can be extreme.
kappa light chain is seen most frequently in patients with The workup for a monoclonal gammopathy
neuropathy.141,142 should begin with serum protein electrophoresis
(SPEP) with high-resolution agarose gel.143 Immuno-
ASSOCIATION WITH NEUROPATHY fixation should be performed when a sharp peak or
When encountering a patient with a neuropathy asso- band is found to differentiate a monoclonal from
ciated with a paraprotein, such as MGUS, the clinician polyclonal increase in Igs, and for detecting a small
must try to determine whether the neuropathy is idio- M-protein in the presence of normal background Igs.
pathic or due to another cause, and thus its association If an M-protein or serum light chain is found, a
with the paraprotein is simply a chance association, or 24-hour urine collection with electrophoresis and
whether the neuropathy is secondary to the process immunofixation should be performed.143,144 In those
causing the paraprotein. Neuropathies associated with without detectable monoclonal proteins, bone marrow
paraproteinemias include distal acquired demyelinating examination usually detects a clonal population of
symmetrical with M-protein (DADS-M) neuropathy plasma cells.145 Mild anemia occurs in 50% of pa-
(also known as a CIDP variant), neuropathy associated tients.21 Electrodiagnostic testing demonstrates a sym-
with primary systemic amyloidosis, neuropathy of PO- metrical, axonal sensorimotor neuropathy. Diagnosis
such as weight loss, fever, or night sweats. Neuropathy What setting? Family history of neuropathy, foot
may be the most common presentation, especially in deformities, onset at any age but often the first through
those with ANNA-1 antibody.148 Other presentations third decades. Absence of systemic symptoms or ac-
include cerebellar syndrome, limbic encephalitis, brain- quired risk factors for neuropathy. Note that a negative
stem dysfunction, and dysautonomia.13,148,150 Most family history does not preclude the possibility of a
often, the effect on the nervous system is multifocal.13 neuropathy caused by a genetic mutation because
The neurological symptoms usually precede the tumor de novo mutations occur frequently and also because
detection.14,148 incomplete penetrance of inherited mutations can occur;
thus, disease may not necessarily manifest in affected
relatives.
Neuropathy
The paraneoplastic neuropathy may present as a sensory
ganglionopathy or sensory-predominant neuropathy, Charcot-Marie-Tooth and Other Inherited
sometimes associated with autonomic neuropathy. Sub- Neuropathies
acute onset with rapid progression is typical.13,148 Sen- Neuropathy caused by a genetic mutation probably
sory symptoms such as paresthesias, dysesthesias, and represents about one third to one half of the neuro-
pain predominate, whereas motor involvement is typi- pathies seen in neurology practice.6 CMT disease (a.k.a.
presents in a distal-predominant distribution. For its prognostic implications. Acta Neurol Scand 1987;75:
the neuropathies associated with inborn errors of 101–105
metabolism, onset of neuropathy may be more sub- 19. McLeod JG. Invited review: autonomic dysfunction in
peripheral nerve disease. Muscle Nerve 1992;15:3–13
acute.154
20. Gertz MA, Merlini G, Treon SP. Amyloidosis and
Waldenström’s macroglobulinemia. Hematology (Am Soc
REFERENCES Hematol Educ Program) 2004:257–282
21. Rajkumar SV, Gertz MA, Kyle RA. Prognosis of patients
1. England JD, Asbury AK. Peripheral neuropathy. Lancet with primary systemic amyloidosis who present with
2004;363:2151–2161 dominant neuropathy. Am J Med 1998;104:232–237
2. Hughes RA. Peripheral neuropathy. BMJ 2002;324:466– 22. Truax BT. Autonomic disturbances in the Guillain-Barre
469 syndrome. Semin Neurol 1984;4:462–468
3. Pourmand R. Evaluating patients with suspected peripheral 23. Pareyson D. Charcot-Marie-Tooth disease and related
neuropathy: do the right thing, not everything. Muscle neuropathies: molecular basis for distinction and diagnosis.
Nerve 2002;26:288–290 Muscle Nerve 1999;22:1498–1509
4. Lubec D, Mullbacher W, Finsterer J, Mamoli B. Diagnostic 24. Kuhlenbaumer G. Mutations in SEPT9 cause hereditary
work-up in peripheral neuropathy: an analysis of 171 cases. neuralgic amyotrophy. Nat Genet 2005;37:1044–1046
Postgrad Med J 1999;75:723–727 25. Burns TM, Phillips LH II, Dimberg EL, Vaught BK, Klein
5. Burns JM, Mauermann ML, Burns TM. An easy approach CJ. Novel myelin protein zero mutation (Arg36Trp) in a
to evaluating peripheral neuropathy. J Fam Pract 2006;55: patient with acute onset painful neuropathy. Neuromuscul
39. Singleton JR, Smith AG, Russell JW, Feldman EL. 56. Wang C, Crapo LM. The epidemiology of thyroid disease
Microvascular complications of impaired glucose tolerance. and implications for screening. Endocrinol Metab Clin
Diabetes 2003;52:2867–2873 North Am 1997;26:189–218
40. Novella SP, Inzucchi SE, Goldstein JM. The frequency of 57. Duyff RF, Van den Bosch J, Laman DM, van Loon BJ,
undiagnosed diabetes and impaired glucose tolerance in Linssen WH. Neuromuscular findings in thyroid dysfunc-
patients with idiopathic sensory neuropathy. Muscle Nerve tion: a prospective clinical and electrodiagnostic study.
2001;24:1229–1231 J Neurol Neurosurg Psychiatry 2000;68:750–755
41. Singleton JR, Smith AG, Bromberg MB. Painful sensory 58. Dyck PJ, Lambert EH. Polyneuropathy associated with
polyneuropathy associated with impaired glucose tolerance. hypothyroidism. J Neuropathol Exp Neurol 1970;29:631–
Muscle Nerve 2001;24:1225–1228 658
42. Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis 59. Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP,
M. The spectrum of neuropathy in diabetes and impaired Allen RH. Prevalence of cobalamin deficiency in the
glucose tolerance. Neurology 2003;60:108–111 Framingham elderly population. Am J Clin Nutr 1994;60:
43. Hoffman-Snyder C, Smith BE, Ross MA, Hernandez J, 2–11
Bosch EP. Value of the oral glucose tolerance test in the 60. Saperstein DS, Wolfe GI, Gronseth GS, et al. Challenges
evaluation of chronic idiopathic axonal polyneuropathy. in the identification of cobalamin-deficiency polyneurop-
Arch Neurol 2006;63:1075–1079 athy. Arch Neurol 2003;60:1296–1301
44. Singleton JR, Smith AG, Bromberg MB. Increased 61. Pratt RW, Weimer LH. Medication and toxin-induced
prevalence of impaired glucose tolerance in patients with peripheral neuropathy. Semin Neurol 2005;25:204–216
painful sensory neuropathy. Diabetes Care 2001;24:1448– 62. Vrancken AF, Kalmijn S, Buskens E, et al. Feasibility and
75. Ferri C, La Civita L, Cirafisi C, et al. Peripheral neuropathy 98. Dalakas MC. Peripheral neuropathy and antiretroviral
in mixed cryoglobulinemia: clinical and electrophysiologic drugs. J Peripher Nerv Syst 2001;6:14–20
investigations. J Rheumatol 1992;19:889–895 99. Brew BJ. The peripheral nerve complications of human
76. Zaltron S, Puoti M, Liberini P. High prevalence of immunodeficiency virus (HIV) infection. Muscle Nerve
peripheral neuropathy in hepatitis C virus infected patients 2003;28:542–552
with symptomatic and asymptomatic cryoglobulinaemia. Ital 100. Brannagan TH III, McAlarney T, Latov N. Peripheral
J Gastroenterol Hepatol 1998;30:391–395 neuropathy in HIV-1 infection. In: Latov N, Wokke JH,
77. Gorevic PD. Cryopathies: cryoglobulins and cryofibrinoge- Kelly JJ Jr, eds. Immunological and Infectious Diseases of
nemia. In: Frank MM, Austen KF, Claman HN, Unanue the Nervous System. Cambridge, UK: Cambridge University
ER, eds. Samters Immunologic Diseases. 5th ed. Vol 2. Press; 1998:285–307
Philadelphia: Little Brown; 1995:951–974 101. Roullet E, Assuerus V, Gozlan J, et al. Cytomegalovirus
78. Kallemuchikkal U, Gorevic PD. Evaluation of cryoglobu- multifocal neuropathy in AIDS: analysis of 15 consecutive
lins. Arch Pathol Lab Med 1999;123:119–125 cases. Neurology 1994;44:2174–2182
79. CDC Web site. Available at: www.cdc.gov. Accessed March 102. Gherardi RK, Chretien F, Delfau-Larue MH, et al.
4, 2007 Neuropathy in diffuse infiltrative lymphocytosis syndrome:
80. Steere AC. Lyme disease. N Engl J Med 2001;345:115–125 an HIV neuropathy, not a lymphoma. Neurology 1998;50:
81. Thaisetthawatkul P, Logigian EL. Peripheral nervous 1041–1044
system manifestations of Lyme borreliosis. J Clin Neuro- 103. Branson BM, Handsfield HH, Lampe MA, et al. Revised
musc Dis 2002;3:165–171 recommendations for HIV testing of adults, adolescents,
82. Pachner AR, Steere AC. The triad of neurologic manifes- and pregnant women in health-care settings. MMWR
119. Dyck PJ, Conn DL, Okazaki H. Necrotizing angiopathic 138. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence
neuropathy. Three-dimensional morphology of fiber degen- of monoclonal gammopathy of undetermined significance.
eration related to sites of occluded vessels. Mayo Clin Proc N Engl J Med 2006;354:1362–1369
1972;47:461–475 139. International Myeloma Working Group. Criteria for the
120. Collins MP, Mendell JR, Periquet MI, et al. Superficial classification of monoclonal gammopathies, multiple mye-
peroneal nerve/peroneus brevis muscle biopsy in vasculitic loma and related disorders: a report of the International
neuropathy. Neurology 2000;55:636–643 Myeloma Working Group. Br J Haematol 2003;121:749–
121. Dyck PJ, Windebank AJ. Diabetic and nondiabetic 757
lumbosacral radiculoplexus neuropathies: new insights into 140. Eurelings M, Lokhorst HM, Kalmijn S, Wokke JH,
pathophysiology and treatment. Muscle Nerve 2002;25: Notermans NC. Malignant transformation in polyneurop-
477–491 athy associated with monoclonal gammopathy. Neurology
122. Simmons Z, Feldman EL. Update on diabetic neuropathy. 2005;64:2079–2084
Curr Opin Neurol 2002;15:595–603 141. Ropper AH, Gorson KC. Neuropathies associated
123. Dyck PJ, Norell JE, Dyck PJ. Microvasculitis and ischemia with paraproteinemia. N Engl J Med 1998;338:1601–
in diabetic lumbosacral radiculoplexus neuropathy. Neurol- 1607
ogy 1999;53:2113–2121 142. Latov N. Pathogenesis and therapy of neuropathies
124. Kaplan JG, Rosenberg R, Reinitz E, Buchbinder S, associated with monoclonal gammopathies. Ann Neurol
Schaumburg HH. Invited review: peripheral neuropathy in 1995;37(S1):S32–S42
Sjögren’s syndrome. Muscle Nerve 1990;13:570–579 143. Kyle RA. Sequence of testing for monoclonal gammopa-
125. Fujibayashi T, Sugai S, Miyasaka N, et al. Revised Japanese thies. Arch Pathol Lab Med 1999;123:114–118