Peripheral Neuropathies

Anwar Wardy W
Departemen Neurologi

FKK - UMJ
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The Peripheral Nervous System

Motor: weakness,
atrophy
Sensory loss

Reflex loss
Autonomic symptoms

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Large Fibers (position)

Small fiber (pain)

(redness, dizziness,
ED)

Peripheral Nerve

Myelin: Current cannot flow

Axon: Not nerves left

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Outline

Facts about peripheral neuropathies

Why is it so hard to diagnose?
High Value

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

Cost perspective

Why payors worry versus why patients worry

Is there a solution?

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How Common Are Treatable

Neuropathies
MMN
CIDP
Diagnosable but
untreatable
Idiopathic
Diabetic

MAYO CLINIC MEDICAL CENTER

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Uncertainty Filter
MMN
CIDP
Fuzzy
Diagnosable but
untreatable
Idiopathic
Diabetic

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University Filter
MMN
CIDP
Diagnosable but
untreatable
Idiopathic
Diabetic

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Pattern Recognition

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Classification

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

TIMING
Acute or chronic?

ASSOCIATED FINDINGS

Painful or painless?

Hereditary or sporadic?

ELECTRODIAGNOSIS
Axonal or demyelinating?

LABORATORY

Paraprotein present? Type?

Antibody against nerve?

CSF protein level?

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HISTOLOGY
Inflammatory Cells

Chronic Length Dependent Neuropathy

Begins in toes or feet

Stocking distribution

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Progresses rostrally
Tops and bottoms of
feet

Weakness begins in
ankles when
sensation reaches
calves

Sometimes diagnosable, Never treatable?

Laboratory Screening for

Treatable Neuropathy?
B12

Not truly length-dependent

Diabetes

This type of neuropathy generally

a late finding

ANA, chronic disease screen

Screen for connective tissue

diseases (late finding)

TSH

If positive, have you proven

anything?

ESR

If onset is recent

HIV

Risk Factors

Review medications

Big question

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Treatable Cases

CADP
MMN

MADSAM

CIDP

Distal

Sensory CIDP

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DADS-M

Phenotype CIDP

Small Differential
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Timeline
Peter Dyck: 1975: a symmetric
sensorimotor neuropathy with a
tendency toward involvement of
the proximal limb muscles
Richard Barohn: 1989: exam
predicts immune responsiveness
The era of CIDP criteria

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Electrodiagnostic Categories
Terminal Slowing

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Focal Conduction Block

Phenotype-MADSAM
Neuropathy

Sensory and Motor

Often painful
Hands more than
ankles
Individual Nerves
Stepwise
Slowing, CB, TD

Prednisone or IVIg (50%)

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Phenotype-MADSAM
Neuropathy

Key DDx:

Brachial plexopathies
Vasculitic
mononeuropathy
multiplex
Compression
neuropathies
HNPP (genetic testing)

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Sensory CIDP

Sensory CIDP (Oh et al.)

Probably in range of 1/1,000 cases of length

dependent neuropathy
Not length dependent
Subacute onset
Conduction block
Steroid responsive

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Multifocal Motor Neuropathy

(MMN)

Almost always in hands

and wrists
Pattern of weakness is in
the distribution of
individual peripheral
nerves

i.e. severe involvement in

ulnar distribution sparing
median

Lack of atrophy in weak

muscles
No pathological reflexes

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Difficult Differential Diagnose

ALS
Other Motor Neuron Presentations
Chronic Radiculopathy
Pinched Nerves (Radial, CTS, Ulnar)

9/18 patients had prior operation

Thoracic outlet

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MMN with Conduction Block

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Covalink GM1 ELISA

High-Titer Positive Results
Diagnosis

Pestronk et al

MMN

23/27 (85%)

CIDP

0/22 (0%)

ALS

0/22 (0%)

Normal controls

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N/A

Antibodies: Length Dependent Neuropathies

DADS-M
Neuropathy
Distal Acquired
Demyelinating
Symmetric Sensory
Neuropathy with IgM

Anti-MAG
IgM only

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10% vs. 2.5%

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Well Defined Immune Disorder?

Myelin widening
Anti-MAG antibody
deposits on myelin
Passive transfer model

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Treatable anti-MAG, IgM

neuropathy?

Reported Beneficial: IVIg, prednisone,

plasmapheresis, interferon-alpha, rituximab,
chlorambucil
Many reports emphasize a decrease in
antibody titers
Athena Diagnostics Lab Report (with
reference)

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Warning
19 patients
1 sustained
response
No hematological
deaths
3 treatment
deaths
7 others
treatment-related
morbidity
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IVIg or Prednisone?

Responsiveness
Costs
Frequent infusion, availability of IVIg
Side-effects of prednisone
Potential serious complications of either drug
IVIg in diabetics, renal insufficiency

Likelihood of diagnosis
Inadequate initial response
Patient preferences

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Uncertainty

(Prognose; Tidak Pasti)

Many cases are not easily definable
because of multiplicity of patterns
Cases that are not clearly untreatable are
possibly treatable

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Thank U, Wassalam Wr, Wbr

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