TheEvaluationof Polyneuropathies - n.neurology.org · symmetric polyneuropathies usually have...

BY TED M BURNS MDMICHELLE L MAUERMANN MD

Polyneuropathy has an estimated preva-lence of 2ndash3 in the general popula-tion and a prevalence as high as 8 inpeople over the age of 55 years1 Roughlyone-third of polyneuropathies will have a

genetic cause one-third an acquired etiology and one-third will be idiopathic despite appropriate diagnosticevaluation2 There are over 100 known acquired andinherited disorders that may cause polyneuropathy afact that presents challenges and can contribute to un-certainty about the scope direction and level of aggres-siveness of any evaluation3 This sometimes leads to a

one-size-fits-all diagnostic strategy a strategy that is un-focused inefficient and costly and sometimes placesthe patient at unnecessary risk of a procedure-relatedcomplication (eg nerve biopsy)

In this article we present a simple and easy-to-remember algorithm for diagnosing polyneuropathybased on first answering 4 clinical questions whatwhere when and what setting (figure 1)3 The 4-stepclinical characterization should almost always be fol-lowed by electrodiagnostic (EDX) characterizationwith appropriate nerve conduction and needle EMGThe clinical and EDX characterization can then becombined as necessary with a consultation of appro-priate tables and lists of differentials or the figure weprovide in this article allowing for the generation ofa focused differential diagnosis and appropriate andefficient evaluation

CLINICAL APPROACH TO NEUROPATHY What

The question ldquowhatrdquo refers to which nerve fiber mo-dalities (sensory motor autonomic or a combination)are involved Identification of sensory nerve involve-ment allows the clinician to exclude from consideration

From the Department of Neurology (TMB) University of VirginiaCharlottesville and Department of Neurology (MLM) Mayo ClinicRochester MN

Address correspondence and reprint requests to Dr Ted M BurnsDepartment of Neurology University of Virginia Charlottesville VA22903 tmb8rvirginiaedu

Author disclosures are provided at the end of the article

Neurologyreg Clinical Practice 201176 (Suppl 2)S6ndashS13

The Evaluation ofPolyneuropathies

S6 Copyright copy 2011 by AAN Enterprises Inc

neuromuscular diseases not associated with sensory dys-function such as myopathies neuromuscular transmis-sion disorders or disease of the anterior horn cell (egamyotrophic lateral sclerosis) When sensory featuresare present the characterization of sensory symptoms asbeing positive or negative can be helpful because mostacquired neuropathies are accompanied by positiveneuropathic sensory symptoms (P-NSS) and most in-herited polyneuropathies are not P-NSS may be pain-ful (ldquoelectric shockrdquo ldquoburningrdquo ldquothrobbingrdquo) orpainless (ldquotinglingrdquo ldquoswellingrdquo ldquobunched-up socksrdquo)Most patients with polyneuropathy have some degree of

motor nerve involvementmdashespecially distally on exam-ination or on EDX testingmdashthat is sometimes over-shadowed by sensory complaints Symptoms suggestingautonomic nerve involvement especially gastrointesti-nal (eg early satiety constipation) cardiovascular(eg orthostatic symptoms) and pupillomotor (egAdie pupil) can be important clues because the num-bers of processes that cause clinically meaningful so-matic plus autonomic polyneuropathy are relatively fewand especially important to diagnose (table 1)45

Where ldquoWhererdquo refers to the distribution of nerve in-volvement in terms of 1) the global distributionthroughout the body and 2) the distribution of involve-ment along the nerves It is important to determinewhether a neuropathic process is length-dependent(eg distal) or not Length-dependent polyneuropa-thies are common and often manifest symmetrically Incontrast patients with non-length-dependent polyneu-ropathies might complain of proximal sensory or motorcomplaints (ie early symptoms in the hands) Distalsymmetric polyneuropathies usually have metabolic

ldquoMost patients with polyneuropathy have

some degree of motor nerve involvementmdash

especially distally on examination or on EDX

testingmdashthat is sometimes overshadowed

by sensory complaintsrdquo

Figure 1 A suggested construct for the approach to neuropathy using the ldquowhat where when and whatsettingrdquo approach for characterizing polyneuropathy

Only the most common etiologies are found in this figure Red font indicates predominantly demyelinating polyneuropathies andyellow font indicates predominantly axonal polyneuropathies CIDP chronic inflammatory demyelinating polyradiculoneuropa-thy CMT Charcot-Marie-Tooth cryo cryoglobulinemia GBS Guillain-Barre syndrome hDMN hereditary distal motorneuropathy (uncommon) HNPP hereditary neuropathy with liability to pressure palsies HSN hereditary sensory neu-ropathy (uncommon) IgM M protein also known as distal acquired demyelinating symmetric (DADS) neuropathy or fre-quently anti-MAG neuropathy MMN multifocal motor neuropathy M protein monoclonal protein N-NSS negativeneuropathic sensory symptoms only P-NSS positive neuropathic sensory symptoms SSN subacute sensory neu-ronopathy (usually associated with malignancy especially small-cell lung cancer) URTI upper respiratory tract infection

Neurology Clinical Practice 76 (Suppl 2) February 15 2011 S7

Table 1 Important patterns of polyneuropathy with focused differentials (rare causes excluded) and proposed laboratory evaluation

Neuropathy pattern Common causes Proposed laboratory studies

Distal symmetric length-dependent neuropathy Diabetes mellitus Fasting blood glucosea

B12 deficiency B12 and methylmalonic acida

MGUS-associated neuropathy Serum protein electrophoresis and immunofixationa

Impaired fasting glucose Oral glucose tolerance testa

Charcot-Marie-Tooth PMP22 duplicationa Cx32a PMP22 deletion MPZ MFN2a

Uremia Creatinine creatinine clearance

Alcohol CBC liver function tests

Hypothyroidism TSH

Thiamine deficiency Whole blood thiamine

Demyelinating poly(radiculo)neuropathies CMT1 PMP22 duplication Cx32 MPZ PMP22 deletion

AIDP CSF

CIDPMADSAMDADS Serum protein electrophoresis and immunofixation CSF

MMN GM1 antibodies

HNPP PMP22 deletion

Somatic neuropathies with prominentautonomic involvement

Diabetes mellitus Fasting blood sugar

AIDP CSF

Primary systemic amyloidosis Serum protein electrophoresis and immunofixation

Sjoumlgren syndrome ESR ANA SS-A SS-B

Vincristine toxicity None

Familial amyloidosis TTR amyloid mass spectrometry

Multifocal neuropathies Systemic and nonsystemic vasculitis CBC wdiff CMP ESR ANA CRP CCP PR3MPO hepatitis B and C serologies cryoglobulinsHIV urinalysis

Entrapment neuropathies None

MADSAM CSF

HNPP PMP22 deletion testing

Axonal polyradiculo(neuro)pathy Lyme Lyme serology and CSF

Sarcoid Serum ACE CSF

AMAN AMSAN CSF

West Nile Serum West Nile serology

Lymphomatouscarcinomatous meningitis CSF with cytology

Sensory neur(on)opathy Diabetes mellitus Fasting blood glucose

B12 deficiency B12 and methylmalonic acid


HIV HIV serology

DADS Serum protein electrophoresis and immunofixation

Paraneoplastic Paraneoplastic antibodies

Leprosy None

Small fiber neuropathy Diabetes mellitus Fasting blood glucose

Impaired glucose tolerance Oral glucose tolerance test



Sarcoidosis Serum ACE



Fabry disease -Galactosidase

HSAN None

Abbreviations AIDP acquired immune demyelinating polyradiculoneuropathy AMAN acute motor axonal neuropathy AMSAN acute motor andsensory axonal neuropathy CIDP chronic immune demyelinating polyradiculoneuropathy DADS distal acquired demyelinating symmetric neuropathyHNPP hereditary neuropathy with liability to pressure palsies HSAN hereditary sensory and autonomic neuropathy MADSAM multifocal acquireddemyelinating sensory and motor neuropathy MGUS monoclonal gammopathy of undetermined significance MMN multifocal motor neuropathyTTR transthyretin-associated neuropathya Recommended by American Academy of Neurology practice parameter12

S8 Neurology Clinical Practice 76 (Suppl 2) February 15 2011

toxic idiopathic or inherited etiologies whereas asym-metric neuropathies are often immune-mediated orinfectious135ndash7 There are of course exceptions such asthe clinical presentation of recurrent painless transientmononeuropathies in hereditary neuropathy with liabilityto pressure palsy Polyneuropathy associated with immu-noglobulin M (IgM) monoclonal protein or anti-MAGautoantibodies is another interesting exception thatpresents with slowly progressive distal and symmetricsensory polyneuropathy Some examples of non-length-dependent asymmetric (acquired) polyneuropathies arepolyradiculopathies (eg Lyme neuroborreliosis)polyradiculoneuropathies (eg Guillain-Barre syn-drome [GBS] chronic inflammatory demyelinatingpolyradiculoneuropathy [CIDP]) dorsal root ganglion-opathies (eg paraneoplastic subacute sensory neu-ronopathy Sjogren-associated sensory ganglionopathy)plexopathies (often immune-mediated) and multiplemononeuropathies (often caused by vasculitis)

When ldquoWhenrdquo refers to the temporal evolutionwhich can be thought of as including the onset andthe progression We prefer to describe symptomonset based on whether or not the neuropathic symp-toms had a convincing date of onset Most immune-mediated or infectious (eg Lyme neuroborreliosis)neuropathies have a definite date of onset A less-exact date of onset suggests a toxicmetabolic inher-ited or idiopathic etiology Symptom onset andtempo often correlate because they both representthe pace of disease progression For example patientswith GBS present with a definite date of onset fol-lowed by rapid progression of impairment and dis-ability Conversely the symptom onset of aninherited polyneuropathy is usually insidious andfollowed by very gradual progression

What setting ldquoWhat settingrdquo refers to the unique clin-ical circumstance of the patient This characterization isdone by considering the patientrsquos past medical historycurrent and past medications social history family his-tory and the review of systems Knowledge of the riskfactors of polyneuropathy and knowledge of symptomsand signs of the risk factors for neuropathy are necessaryto take advantage of this information When construct-ing the patientrsquos clinical setting the clinician must re-member to consider first the common causes ofpolyneuropathy (eg diabetes alcohol inherited) andsearch aggressively for any clinical clues that might sug-gest these etiologies This is perhaps most importantwhen evaluating a patient for an inherited polyneurop-athy particularly given how common they are At aminimum the clinician should ask specifically abouteach first-degree relative for example ldquoDid either par-ent or any sibling have foot problems similar to yoursrdquoPatients should also be asked at follow-up visits as pa-

tients often learn important family medical informationonly after their own diagnosis Family members shouldbe examined whenever possible By doing this clues areoften uncovered that would have otherwise never beenObtaining a precise history of alcohol intake is also veryimportant and in our experience often performed per-functorily by others It is often illuminating to probeinto an alcohol consumption history in a thoroughnonjudgmental and nonthreatening way8 Past medicaland medication history are also important consider-ations for elaborating the patientrsquos unique clinical set-ting Diabetes renal disease malnutrition HIV andparaproteinemia are some of the disorders that are riskfactors Toxic polyneuropathy caused by medication iscommon in the setting of certain chemotherapeutic oranti-HIV treatment exposures (table 2)19 Age is an-other important consideration young patients aremuch more likely to have a polyneuropathy on a geneticbasis elderly patients are much more likely to have idio-pathic polyneuropathy and middle-age patients aremore likely to have acquired polyneuropathy

The physician must also consider whether the rest ofthe characterization (ie ldquowhatrdquo ldquowhererdquo ldquowhenrdquo

Table 2 Some medications that maycause polyneuropathy

Anti-infectious medications

Chloroquine

Dapsone

Isoniazid

Metronidazole

Nitrofurantoin

Dideoxycytidine and other nucleoside analogs

Chemotherapy and anticancer medications

Cisplatinum

Taxanes (paclitaxel and docetaxel)

Suramin

Thalidomide

Vincristine

Bortezomib

Antirheumatic and immunosuppressants

Chloroquine

Colchicine

Cardiovascular medications

Amiodarone

Hydralazine

Perhexiline

Propafenone

Psychiatric and sedatives

Disulfiram

Other medications

Pyridoxine (vitamin B6)

Phenytoin


characterization) fits with the clinical setting and alsomust consider other possible etiologies before implicat-ing an etiology For example the comorbidity of diabe-tes in a patient with polyneuropathy does notnecessarily prove diabetes is causative10 The exami-nation must also corroborate with the overall charac-terization For example we recently evaluated a38-year-old man with diabetes complaining of sen-sory symptoms in the hands and feet whose examina-tion demonstrated not only sensory loss but alsopathologically brisk reflexes prompting a workupthat led to the diagnosis of large disk herniation caus-ing a cervical myelopathy

Electrodiagnostic testing The fifth step for charac-terizing a polyneuropathy utilizes EDX testingEDX can confirm or refute the clinical character-ization in terms of ldquowhatrdquo and ldquowhererdquo and to alesser extent ldquowhenrdquo EDX can also characterizethe polyneuropathy as being primarily axonal ordemyelinating The metabolictoxic and idio-pathic neuropathies usually manifest with promi-nent axonal injury whereas immune-mediated andinherited neuropathies may be either predomi-nantly axonal or predominantly demyelinatingFor example GBS and CIDP are 2 relatively com-mon demyelinating immune-mediated poly(radi-culo) neuropathies Charcot-Marie-Tooth (CMT)disease 1 the most common group of inheritedsensorimotor polyneuropathies is predominantlydemyelinating whereas CMT2 is predominantly ax-onal Nerve conduction studies are particularly help-ful here as patients with CMT1 will have uniformslowing of motor conduction velocities almost al-ways 35 ms in the upper extremities and 28ms in the lower extremities EDX can also helpsearch for subclinical involvement and providebaseline parameters in case future EDX is neces-sary to monitor the patientrsquos course EDX will benormal in small-fiber polyneuropathy11

A detailed review of the important causes ofpolyneuropathy is beyond the scope of this reviewPlease consult other articles and chapters for infor-mation and for additional references about the individ-ual causes of neuropathy See table 1 for a list ofcommon etiologies and proposed laboratory testing forvarious patterns of polyneuropathy See table 2 for a listof some medications that can cause polyneuropathy

INCORPORATION OF PRACTICE PARAMETERSINTO THE EVALUATION OF DISTAL SYMMETRICPOLYNEUROPATHY Two practice parameters werepublished in 2009 that provide recommendations forthe evaluation of distal symmetric polyneuropathy(DSP) These publications were reports of the Amer-ican Academy of Neurology American Association

of Neuromuscular and Electrodiagnostic Medicineand the American Academy of Physical Medicineand Rehabilitation1213 The parameters were pub-lished to provide physicians with evidence-basedguidelines for the evaluation of DSP It is importantto remember that these evidence-based guidelines areonly about diagnostic testing for the DSP phenotypeand thus do not supplant the need for a clinicalevaluation and EDX characterization of the polyneu-ropathy For example they were not designed to pro-vide diagnostic recommendations that substitute fora careful and comprehensive history eg one that que-ries patients about alcohol use or family history andother important details of the individualrsquos history andexamination The authors wrote that the ldquocause of mostpolyneuropathies is evident when the information ob-tained from the medical history neurologic examina-tion and EDX studies are combined with simplescreening laboratory tests hellip Laboratory tests must beinterpreted in the context of other clinical informationsince the etiologic yield of laboratory testing alone islimited by the low specificity of many of the testsrdquo12

The authors of the practice parameters note that moststudies suggest that the following laboratory tests are indi-cated for DSP complete blood count erythrocyte sedi-mentation rate comprehensive metabolic panel thyroidfunction tests serum B12 and serum protein immuno-fixation electrophoresis The evidence is currently mostcompelling for blood glucose serum B12 and serumprotein immunofixation electrophoresis of which thetest with the highest yield is blood glucose which comesas no surprise knowing that diabetic polyneuropathy isthe most common cause of DSP

Diabetic polyneuropathy (DPN) symptoms are of-ten predated by silent dysfunction of the nerves withfew symptoms but with progression P-NSS and signspredominate Onset is fairly gradual and the progres-sion is usually slow14 Diabetes mellitus (DM) also ap-pears to be a risk factor for the development oflumbosacral radiculoplexus neuropathy (LRPN)among other less common patterns of neuropathy asso-ciated with DM The presentation of diabetic LRPN(DLRPN) differs dramatically from DPN with pa-tients experiencing unilateral or asymmetric proximallower extremity pain and weakness with a definite dateof onset DLRPN is a microvasculitic neuropathy andis best classified as an immune-mediated radiculoplexus

Approach to Polyneuropathy

bull Answer ldquowhat when where what settingrdquobull Perform electrodiagnosticsbull Use laboratory testing judiciouslybull Treat as appropriate


neuropathy rather than a metabolic neuropathy15 Im-paired fasting glucose is defined as a plasma glucose levelgreater than 100 and less than 126 mgdL impairedglucose tolerance as a 2-hour glucose level between 140and 199 mgdL after a 75-g oral glucose load (GTT)16

Impaired glucose metabolism has recently beensuggested as a cause of chronic idiopathic axonal neu-ropathy especially painful distal symmetric polyneu-ropathy Many specialists suggest that the 2-hour oralGTT is a more sensitive measure of abnormal glucosemetabolism compared to fasting plasma glucose orHgA1c The authors of the practice parameter wrotethat ldquowhen routine blood glucose testing is not clearlyabnormal other tests for prediabetes (impaired glucosetolerance) such as GTT may be considered in patientswith distal symmetric sensory polyneuropathy espe-cially if accompanied by painrdquo12

Vitamin B12 deficiency is relatively frequently ab-normal in patients with DSP In addition to serum B12levels serum methylmalonic acid and homocysteinelevels are sensitive indicators of B12 deficiency withserum methylmalonic acid levels being more specific17

Monoclonal gammopathy of undetermined sig-nificance (MGUS) is common in the adult popula-tion occurring for example in 3 of people overage 50 Monoclonal gammopathies are more com-mon in patients with DSP than in the normal popu-lation18 Thus for patients with DSP and a serummonoclonal protein the clinician must determinewhether or not the polyneuropathy is coincidental orsecondary to the paraproteinemia Polyneuropathiesassociated with paraproteinemias include distal ac-quired demyelinating symmetric (DADS-M)neuropathy (also known as an ataxic sensory-

Figure 2 Decision algorithm for use in cases of suspect hereditary polyneuropathy using family history andelectrodiagnostic characterization

Reprinted with permission from England JD Gronseth GS Franklin G et al Practice parameter evaluation of distal symmetric polyneuropathy role oflaboratory and genetic testing (an evidence-based review) report of the American Academy of Neurology American Association of Neuromuscular andElectrodiagnostic Medicine and American Academy of Physical Medicine and Rehabilitation Neurology 200972185ndash19212


predominant CIDP variant) neuropathy associatedwith primary systemic amyloidosis neuropathy ofpolyneuropathy organomegaly endocrinopathy Mprotein and skin changes (POEMS) syndrome andneuropathy associated with Waldenstrom macro-globulinemia The history and EDX testing are par-ticularly helpful in sorting out whether theparaprotein in a patient with polyneuropathy is coin-cidental or causal especially if the physician remem-bers the following 1) accompanying systemicsymptoms (eg fatigue weight loss) raise concernfor primary systemic amyloidosis POEMS or malig-nancy 2) autonomic symptoms and signs (eg or-thostatic hypotension) are common in primarysystemic amyloidosis 3) EDX features of primary de-myelination are commonly seen in neuropathies ofDADS-M and POEMS 4) the neuropathy is usuallyaxonal when associated with Waldenstrom macro-globulinemia and primary systemic amyloidosis and5) sensory ataxia is a prominent feature of IgM-related polyneuropathies such as those associatedwith DADS-M and Waldenstrom macroglobuline-mia Patients with DADS-M neuropathy also oftenhave serum antibodies to myelin-associated glycop-rotein (MAG)19 Conversely a coincidental associa-tion between the paraprotein (eg MGUS) and thepolyneuropathy would be more likely in a patientover the age of 50 with a chronic distal axonal sym-metric polyneuropathy who lacks prominent ataxiaand any systemic or autonomic accompaniments

DSP is the predominant phenotype in the heredi-tary polyneuropathies and consequently the practiceparameter also addresses the role of genetic testing12

Pattern of inheritance and electrodiagnostic character-ization are 2 particularly important etiologic variablesfor an inherited polyneuropathy Most cases of CMTare of the demyelinating form (CMT1) Most cases ofCMT1 (eg 70) are caused by duplication of thePMP22 gene (ie CMT1A) Most cases of axonalCMT (CMT2) are caused by mutations of MFN2Cx32 (GJB1) mutations caused the vast majority ofX-linked polyneuropathy which may be predomi-nantly demyelinating or predominantly axonal The au-thors recommend that a stepwise evaluation of possiblehereditary polyneuropathy be considered in order toimprove the efficiency of the evaluation EDX charac-terization of suspected hereditary DSP should be per-formed followed by an evidence-based tiered approach(figure 2)12

The authors of the practice parameter also recom-mend that autonomic testing be considered in pa-tients with polyneuropathy and autonomicdysfunction that nerve biopsy is generally acceptedfor patients when amyloid neuropathy or vasculitic neu-

ropathy is suspected and for some atypical forms ofCIDP and that skin biopsy is a validated technique fordetermining intraepidermal nerve fiber density and maybe considered for the diagnosis of DSP particularlysmall fiber sensory polyneuropathy13

DISCLOSUREDr Burns serves as Podcast Editor for Neurologyreg performs EMG studies

in his neuromuscular practice (30 effort) and has received research

support from the Myasthenia Gravis Foundation of America and Knopp

Neurosciences Inc Dr Mauermann performs EMG studies in her prac-

tice (30 effort) and receives research support from Pfizer Inc and NIH

NINDS

Received October 18 2010 Accepted in final form December 16 2010

REFERENCES1 England JD Asbury AK Peripheral neuropathy Lancet

20043632151ndash21612 Dyck PJ Oviatt KF Lambert EH Intensive evaluation of

referred unclassified neuropathies yields improved diagno-sis Ann Neurol 198110222ndash226

3 Mauermann ML Burns TM The evaluation of chronic ax-onal polyneuropathies Semin Neurol 200728133ndash151

4 Barohn RJ Approach to peripheral neuropathy and neu-ronopathy Semin Neurol 1998187ndash18

5 Willison HJ Winer JB Clinical evaluation and investiga-tion of neuropathy J Neurol Neurosurg Psychiatry 200374(suppl II)ii3ndashii8

6 Hughes RA Peripheral neuropathy BMJ 2002324466ndash4697 Bromberg MB Smith AG Toward an efficient method to

evaluate peripheral neuropathies J Clin Neuromuscul Dis20023172ndash182

8 Koike H Iijima M Sugiura M et al Alcoholic neuropa-thy is clinicopathologically distinct from thiamine-deficiency neuropathy Ann Neurol 20035419ndash29

9 Lewis RA Toxic and deficiency neuropathies ContinuumLifelong Learning Neurol 20039160ndash181

10 Gorson KC Ropper AH Additional causes for distal sen-sory polyneuropathy in diabetic patients J Neurol Neuro-surg Psychiatry 200677354ndash358

11 Lacomis D Small-fiber neuropathy Muscle Nerve 200226173ndash188

12 England JD Gronseth GS Franklin G et al Practice pa-rameter evaluation of distal symmetric polyneuropathyrole of laboratory and genetic testing (an evidence-basedreview) report of the American Academy of NeurologyAmerican Association of Neuromuscular and Electrodiag-nostic Medicine and American Academy of Physical Med-icine and Rehabilitation Neurology 200972185ndash192

13 England JD Gronseth GS Franklin G et al Practice pa-rameter evaluation of distal symmetric polyneuropathyrole of autonomic testing nerve biopsy and skin biopsy(an evidence-based review) report of the American Acad-emy of Neurology American Association of Neuromuscu-lar and Electrodiagnostic Medicine and AmericanAcademy of Physical Medicine and Rehabilitation Neu-rology 200972177ndash184

14 Sinnreich M Taylor BV Dyck PJ Diabetic neuropathiesclassification clinical features and pathophysiological ba-sis Neurologist 20051163ndash79

15 Dyck PJ Norell JE Dyck PJ Microvasculitis and ischemiain diabetic lumbosacral radiculoplexus neuropathy Neu-rology 1999532113ndash2121


16 Smith AG Singleton JR Idiopathic neuropathy prediabetesand the metabolic syndrome J Neurol Sci 20062429ndash14

17 Saperstein DS Wolfe GI Gronseth GS et al Challengesin the identification of cobalamin-deficiency polyneurop-athy Arch Neurol 2003601296ndash301

18 Ropper AH Gorson KC Neuropathies associatedwith paraproteinemia N Engl J Med 19983381601ndash1607

19 Saperstein DS Chronic acquired demyelinating polyneu-ropathies Semin Neurol 200828168ndash184

If you liked this article you may be interested in NeurologyEngland et al Practice Parameter Evaluation of distal symmetric polyneuropathy Role of auto-nomic testing nerve biopsy and skin biopsy (an evidence-based review) Report of the AmericanAcademy of Neurology American Association of Neuromuscular and Electrodiagnostic Medicineand American Academy of Physical Medicine and Rehabilitation January 13 2009wwwneurologyorg

England et al Practice Parameter Evaluation of distal symmetric polyneuropathy Role of labora-tory and genetic testing (an evidence-based review) Report of the American Academy of Neurol-ogy American Association of Neuromuscular and Electrodiagnostic Medicine and AmericanAcademy of Physical Medicine and Rehabilitation January 13 2009 wwwneurologyorg

Palla et al Deficient high-acceleration vestibular function in patients with polyneuropathy June 92009 wwwneurologyorg

Kuijf et al Detection of anti-MAG antibodies in polyneuropathy associated with IgM monoclonalgammopathy September 1 2009 wwwneurologyorg

Layzer et al Myeloma-associated polyneuropathy responding to lenalidomide September 82009 wwwneurologyorg

Niermeijer et al Prognosis of polyneuropathy due to IgM monoclonal gammopathy A prospectivecohort study February 2 2010 wwwneurologyorg

Julie Rowin MR imaging of demyelinating hypertrophic polyneuropathy April 6 2010wwwneurologyorg

Neurology NowMichael Smolinsky Neuropathy testing JanuaryFebruary 2009 wwwneurologynowcom

Michael Smolinsky Neuropathy caregiver blog MarchApril 2010 wwwneurologynowcom

Neurology TodayJamie Talan Whole-genome sequencing reveals mutations for Charcot-Marie-Tooth neuropathy Aglimpse into the future of personalized medicine May 6 2010 wwwneurotodayonlinecom

Kurt Samson Relapse patters may help discern Guillain-Barre syndrome from acute CIDP May20 2010 wwwneurotodayonlinecom


DOI 101212WNL0b013e31820c3622201176S6-S13 Neurology

Ted M Burns and Michelle L MauermannThe Evaluation of Polyneuropathies

This information is current as of February 14 2011

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neuromuscular diseases not associated with sensory dys-function such as myopathies neuromuscular transmis-sion disorders or disease of the anterior horn cell (egamyotrophic lateral sclerosis) When sensory featuresare present the characterization of sensory symptoms asbeing positive or negative can be helpful because mostacquired neuropathies are accompanied by positiveneuropathic sensory symptoms (P-NSS) and most in-herited polyneuropathies are not P-NSS may be pain-ful (ldquoelectric shockrdquo ldquoburningrdquo ldquothrobbingrdquo) orpainless (ldquotinglingrdquo ldquoswellingrdquo ldquobunched-up socksrdquo)Most patients with polyneuropathy have some degree of

motor nerve involvementmdashespecially distally on exam-ination or on EDX testingmdashthat is sometimes over-shadowed by sensory complaints Symptoms suggestingautonomic nerve involvement especially gastrointesti-nal (eg early satiety constipation) cardiovascular(eg orthostatic symptoms) and pupillomotor (egAdie pupil) can be important clues because the num-bers of processes that cause clinically meaningful so-matic plus autonomic polyneuropathy are relatively fewand especially important to diagnose (table 1)45

Where ldquoWhererdquo refers to the distribution of nerve in-volvement in terms of 1) the global distributionthroughout the body and 2) the distribution of involve-ment along the nerves It is important to determinewhether a neuropathic process is length-dependent(eg distal) or not Length-dependent polyneuropa-thies are common and often manifest symmetrically Incontrast patients with non-length-dependent polyneu-ropathies might complain of proximal sensory or motorcomplaints (ie early symptoms in the hands) Distalsymmetric polyneuropathies usually have metabolic

ldquoMost patients with polyneuropathy have

some degree of motor nerve involvementmdash

especially distally on examination or on EDX

testingmdashthat is sometimes overshadowed

by sensory complaintsrdquo

Figure 1 A suggested construct for the approach to neuropathy using the ldquowhat where when and whatsettingrdquo approach for characterizing polyneuropathy

Only the most common etiologies are found in this figure Red font indicates predominantly demyelinating polyneuropathies andyellow font indicates predominantly axonal polyneuropathies CIDP chronic inflammatory demyelinating polyradiculoneuropa-thy CMT Charcot-Marie-Tooth cryo cryoglobulinemia GBS Guillain-Barre syndrome hDMN hereditary distal motorneuropathy (uncommon) HNPP hereditary neuropathy with liability to pressure palsies HSN hereditary sensory neu-ropathy (uncommon) IgM M protein also known as distal acquired demyelinating symmetric (DADS) neuropathy or fre-quently anti-MAG neuropathy MMN multifocal motor neuropathy M protein monoclonal protein N-NSS negativeneuropathic sensory symptoms only P-NSS positive neuropathic sensory symptoms SSN subacute sensory neu-ronopathy (usually associated with malignancy especially small-cell lung cancer) URTI upper respiratory tract infection











Hypothyroidism TSH



AIDP CSF


MMN GM1 antibodies

HNPP PMP22 deletion



AIDP CSF







MADSAM CSF




AMAN AMSAN CSF






HIV HIV serology



Leprosy None









HSAN None










Chloroquine

Dapsone

Isoniazid

Metronidazole

Nitrofurantoin



Cisplatinum


Suramin

Thalidomide

Vincristine

Bortezomib


Chloroquine

Colchicine


Amiodarone

Hydralazine

Perhexiline

Propafenone


Disulfiram

Other medications


Phenytoin





























NINDS










































Citations










Reprints













Hypothyroidism TSH



AIDP CSF


MMN GM1 antibodies

HNPP PMP22 deletion



AIDP CSF







MADSAM CSF




AMAN AMSAN CSF






HIV HIV serology



Leprosy None









HSAN None










Chloroquine

Dapsone

Isoniazid

Metronidazole

Nitrofurantoin



Cisplatinum


Suramin

Thalidomide

Vincristine

Bortezomib


Chloroquine

Colchicine


Amiodarone

Hydralazine

Perhexiline

Propafenone


Disulfiram

Other medications


Phenytoin





























NINDS










































Citations










Reprints











Chloroquine

Dapsone

Isoniazid

Metronidazole

Nitrofurantoin



Cisplatinum


Suramin

Thalidomide

Vincristine

Bortezomib


Chloroquine

Colchicine


Amiodarone

Hydralazine

Perhexiline

Propafenone


Disulfiram

Other medications


Phenytoin





























NINDS










































Citations










Reprints































NINDS










































Citations










Reprints



























Citations










Reprints




TheEvaluationof Polyneuropathies - n.neurology.org · symmetric polyneuropathies usually have...

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