Periferal Neuropathy 06

anwar wardyanwar wardy

Peripheral NeuropathiesPeripheral Neuropathies

Anwar Wardy WAnwar Wardy W

Departemen NeurologiDepartemen Neurologi

FKK - UMJFKK - UMJ


The Peripheral Nervous SystemThe Peripheral Nervous System

• Motor: weakness, Motor: weakness, atrophyatrophy

• Sensory lossSensory loss• Large Fibers (position)Large Fibers (position)• Small fiber (pain)Small fiber (pain)

• Reflex lossReflex loss• Autonomic symptomsAutonomic symptoms

• (redness, dizziness, (redness, dizziness, ED)ED)


Peripheral NervePeripheral Nerve

• Myelin: Current cannot flowMyelin: Current cannot flow• Axon: Not nerves leftAxon: Not nerves left


OutlineOutline

• Facts about peripheral neuropathiesFacts about peripheral neuropathies• Why is it so hard to diagnose?Why is it so hard to diagnose?• ““High Value”High Value”

• What is common?What is common?• What is dangerous?What is dangerous?• What is responsive to immunotherapy?What is responsive to immunotherapy?

• Cost perspectiveCost perspective• Why payors worry versus why patients worryWhy payors worry versus why patients worry• Is there a solution?Is there a solution?


How Common Are Treatable How Common Are Treatable NeuropathiesNeuropathies

MMN

CIDP

Diagnosable butuntreatableIdiopathic

Diabetic

MAYO CLINIC MEDICAL CENTER


MMN

CIDP

Fuzzy


Diabetic

““Uncertainty Filter”Uncertainty Filter”


MMN

CIDP


Diabetic

““University Filter”University Filter”


Pattern RecognitionPattern Recognition


ClassificationClassificationEXAMINATION FINDINGSEXAMINATION FINDINGS

• Purely Motor or Sensory or Sensorimotor?Purely Motor or Sensory or Sensorimotor?• Proximal or distal? Symmetric or asymmetric?Proximal or distal? Symmetric or asymmetric?• Multifocal, generalized, regional?Multifocal, generalized, regional?• Upper limbs, lower limbs, neck, trunk?Upper limbs, lower limbs, neck, trunk?

TIMINGTIMING• Acute or chronic?Acute or chronic?

ASSOCIATED FINDINGSASSOCIATED FINDINGS• Painful or painless?Painful or painless?• Hereditary or sporadic?Hereditary or sporadic?

ELECTRODIAGNOSISELECTRODIAGNOSIS• Axonal or demyelinating?Axonal or demyelinating?

LABORATORYLABORATORY• Paraprotein present? Type?Paraprotein present? Type?

• Antibody against nerve?Antibody against nerve?• CSF protein level?CSF protein level?

HISTOLOGYHISTOLOGY• Inflammatory CellsInflammatory Cells


Chronic Length Dependent NeuropathyChronic Length Dependent Neuropathy

• Begins in toes or feetBegins in toes or feet• Stocking distributionStocking distribution

• Progresses rostrallyProgresses rostrally• Tops and bottoms of Tops and bottoms of

feetfeet

• Weakness begins in Weakness begins in ankles when ankles when sensation reaches sensation reaches calvescalves

Sometimes diagnosable, Never treatable?Sometimes diagnosable, Never treatable?


Laboratory Screening for Laboratory Screening for “Treatable” Neuropathy?“Treatable” Neuropathy?

•B12B12 Not truly length-dependentNot truly length-dependent

•DiabetesDiabetes This type of neuropathy generally This type of neuropathy generally a late findinga late finding

•ANA, chronic disease screenANA, chronic disease screen Screen for connective tissue Screen for connective tissue diseases (late finding)diseases (late finding)

•TSHTSH If positive, have you proven If positive, have you proven anything?anything?

•ESRESR If onset is recentIf onset is recent

•HIVHIV Risk FactorsRisk Factors

•Review medicationsReview medications Big questionBig question


CADPCADP

MMN

CIDP Distal

MADSAM

Sensory CIDP DADS-M

Treatable Cases


Phenotype CIDPPhenotype CIDP

Small DifferentialSmall Differential


TimelineTimeline

• Peter Dyck: 1975: “…a symmetric Peter Dyck: 1975: “…a symmetric sensorimotor neuropathy with a sensorimotor neuropathy with a tendency toward involvement of tendency toward involvement of the proximal limb muscles…” the proximal limb muscles…”

• Richard Barohn: 1989: exam Richard Barohn: 1989: exam predicts immune responsivenesspredicts immune responsiveness

• The era of CIDP criteriaThe era of CIDP criteria


Electrodiagnostic CategoriesElectrodiagnostic Categories

Terminal Slowing Focal Conduction Block


Phenotype-MADSAM Phenotype-MADSAM NeuropathyNeuropathy

• Sensory and MotorSensory and Motor• Often painfulOften painful• Hands more than Hands more than

anklesankles• Individual NervesIndividual Nerves• StepwiseStepwise• Slowing, CB, TDSlowing, CB, TD• Prednisone or IVIg (50%)Prednisone or IVIg (50%)


Phenotype-MADSAM Phenotype-MADSAM NeuropathyNeuropathy

• Key DDx: Key DDx: • Brachial plexopathiesBrachial plexopathies• Vasculitic Vasculitic

mononeuropathy mononeuropathy multiplexmultiplex

• Compression Compression neuropathiesneuropathies

• HNPP (genetic testing)HNPP (genetic testing)


Sensory CIDPSensory CIDP

• ““Sensory CIDP” (Oh et al.)Sensory CIDP” (Oh et al.)• Probably in range of 1/1,000 cases of length Probably in range of 1/1,000 cases of length

dependent neuropathydependent neuropathy• Not length dependent Not length dependent • Subacute onsetSubacute onset• Conduction blockConduction block• Steroid responsiveSteroid responsive


Multifocal Motor Neuropathy Multifocal Motor Neuropathy (MMN)(MMN)

• Almost always in hands Almost always in hands and wrists and wrists

• Pattern of weakness is in Pattern of weakness is in the distribution of the distribution of individual peripheral individual peripheral nervesnerves

• i.e. severe involvement in i.e. severe involvement in ulnar distribution sparing ulnar distribution sparing medianmedian

• Lack of atrophy in weak Lack of atrophy in weak musclesmuscles

• No pathological reflexesNo pathological reflexes


Difficult Differential DiagnoseDifficult Differential Diagnose

• ALSALS• Other Motor Neuron PresentationsOther Motor Neuron Presentations• Chronic Radiculopathy Chronic Radiculopathy • Pinched Nerves (Radial, CTS, Ulnar)Pinched Nerves (Radial, CTS, Ulnar)

• 9/18 patients had prior operation9/18 patients had prior operation

• Thoracic outletThoracic outlet


MMN with Conduction BlockMMN with Conduction Block


Covalink GM1 ELISACovalink GM1 ELISAHigh-Titer Positive ResultsHigh-Titer Positive Results


Antibodies: Length Dependent NeuropathiesAntibodies: Length Dependent Neuropathies

Anti-MAG

DADS-M Neuropathy

Distal Acquired Demyelinating

Symmetric Sensory Neuropathy with IgM

IgM only


•10% vs. 2.5%


Well Defined Immune Disorder?Well Defined Immune Disorder?

• Myelin wideningMyelin widening• Anti-MAG antibody Anti-MAG antibody

deposits on myelindeposits on myelin• Passive transfer modelPassive transfer model


Treatable anti-MAG, IgM Treatable anti-MAG, IgM neuropathy?neuropathy?

• Reported Beneficial: IVIg, prednisone, Reported Beneficial: IVIg, prednisone, plasmapheresis, interferon-alpha, rituximab, plasmapheresis, interferon-alpha, rituximab, chlorambucilchlorambucil

• Many reports emphasize a decrease in Many reports emphasize a decrease in antibody titersantibody titers

• Athena Diagnostics Lab Report (with Athena Diagnostics Lab Report (with reference)reference)


19 patients

1 sustained response

No hematological deaths

3 treatment deaths

7 others treatment-related

morbidity

Warning…


IVIg or Prednisone?IVIg or Prednisone?

• ResponsivenessResponsiveness• CostsCosts• Frequent infusion, availability of IVIgFrequent infusion, availability of IVIg• Side-effects of prednisoneSide-effects of prednisone• Potential serious complications of either drugPotential serious complications of either drug

• IVIg in diabetics, renal insufficiencyIVIg in diabetics, renal insufficiency• Likelihood of diagnosisLikelihood of diagnosis• Inadequate initial responseInadequate initial response• Patient preferencesPatient preferences


UncertaintyUncertainty(Prognose; Tidak Pasti)(Prognose; Tidak Pasti)

• Many cases are not easily definable Many cases are not easily definable because of multiplicity of patternsbecause of multiplicity of patterns

• Cases that are not clearly untreatable are Cases that are not clearly untreatable are possibly treatablepossibly treatable


• Thank UThank U, Wassalam Wr, Wbr, Wassalam Wr, Wbr

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Periferal Neuropathy 06