Peripheral Neuropathies

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Peripheral Neuropathies

• Jonathan Katz, MD
• Director Neuromuscular Center
• CPMC
• San Francisco, CA

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The Peripheral Nervous System

• Motor weakness, atrophy
• Sensory loss
• Large Fibers (position)
• Small fiber (pain)
• Reflex loss
• Autonomic symptoms
• (redness, dizziness, ED)

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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
MAYO CLINIC SOUTHWESTERN MEDICAL CENTER, DALLAS
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Uncertainty Filter
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University Filter
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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?
• HISTOLOGY
• Inflammatory Cells

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Chronic Length Dependent Neuropathy

• Begins in toes or feet
• Stocking distribution
• Progresses rostrally
• Tops and bottoms of feet
• Weakness begins in ankles when sensation reaches
  calves

Sometimes diagnosable, Never treatable?
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Laboratory Screening for Treatable Neuropathy?
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Treatable Cases
CADP
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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
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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

• 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 ELISAHigh-Titer Positive Results
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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 Benefit and Cost Perspective
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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

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

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Costs?

• 0 Do nothing
• 15 Prednisone IVIg 75/gram
• 500 Physical Therapy
• 3000 Imuran, CellCept, Others
• 10,000 Pheresis
• 12000 IVIg
• Immeasurable Dies from steroids or IVIg