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CHRONIC IMMUNE POLYNEUROPATHIES: DEMYELINATING

Demyelinating PN
  Comparative features
  Treatment strategies

CIDP
  Clinical features
    Associated disorders
  Laboratory features
  Pathology
  Treatments
  Variants
Contactin-1
GALOP syndrome
GD1a antibody
  Motor-Sensory neuropathy
Multifocal motor neuropathy
MAG antibody associated neuropathy
Neurofascin antibodies
Osteosclerotic Myeloma
Other demyelinating neuropathies
POEMS Syndrome
Sulfatide

Antibody testing

Also see: Immune axonal neuropathies


Multifocal Motor Neuropathy (MMN)
Myelinated Axons: Segmental demyelination


CHRONIC IMMUNE DEMYELINATING NEUROPATHIES:
COMPARATIVE FEATURES
Neuropathy
(Antibody)
Clinical Features Electrophysiology Antibody M-Protein* Treatment
Chronic
Immune
Demyelinating
Polyneuropathy
(CIDP)
Motor > Sensory
Weakness:
  Proximal & Distal
  Symmetric
Onset: 1 to 80 yrs
Chronic/Relapsing
Motor + Sensory Δ
NCV: Slow
Conduction Block
Distal Latency: Long
F-waves: Slow
Targets
  β-tubulin
  Heparan sulfate

Class: IgM or IgG
Frequency: 10%
15% T-cell immunosuppression
  Prednisone
  Cyclosporine A
  Methotrexate
HIG
Plasma Exchange
Multifocal
  CIDP


Also see:
  CIDP variants
Chronic
Motor > Sensory
Weakness:
  Distal > Proximal
  Asymmetric
  Arms > Legs
Onset: 15 to 75 yrs
Motor + Sensory Δ
NCV: Slow
Conduction Block
Distal Latency: Long
F-waves: Slow
? ? T-cell immunosuppression
  Prednisone
HIG
Multifocal
Motor
Neuropathy

(MMN)
Motor only
  Distal > Proximal
  Arms > Legs
  Asymmetric
Onset: 25 to 80 yrs
Slowly progressive
Motor only
  Conduction Block
  Axon Loss: Distal

EMG: Denervation with
  disease progression
Targets
  Co-GM1, NP-9
    or NS6S


Class: IgM

Frequency: 80%
20% IVIg (Conduction block)
B-cell immunosuppression
  Cyclophosphamide ±
    Plasma Exchange
  Rituximab
Myelin-
Associated
Glycoprotein

(MAG)
Sensory > Motor
Distal; Symmetric
Gait disorder
Tremor
Onset: > 50 yrs
Slowly progressive
Motor + Sensory Δ
Distal Latency: Long
NCV: Slow
No conduction block
Axon Loss: Distal legs
Target: MAG

Class: IgM

Frequency: 100%
85% B-cell immunosuppression
  Cyclophosphamide ±
    Plasma Exchange
  Rituximab
  ? Fludarabine
  Not HIG
GALOP Gait Disorder
Sensory > Motor
Distal; Symmetric
Onset: > 50 yrs
Motor + Sensory Δ
Distal Latency: Long
NCV: Slow
No conduction block
Target
  Sulfatide in
    lipid membrane


Class: IgM
80% HIG
  Cyclophosphamide ±
    Plasma Exchange
Sulfatide Slowly progressive
Sensory > Motor
Distal; Symmetric
Onset: > 45 yrs
Distal Latency: Long
NCV: Slow
Axon Loss: Distal
Target
  Sulfatide

Class: IgM
90% HIG
Cyclophosphamide ±
    Plasma Exchange
GM2 &
GalNAc-GD1a

Sensory > Motor
Ataxia: Limb & Gait
Distal
Symmetric or
  Asymmetric
Onset: Adult
Slowly progressive
NCV: Slow
Targets
  GM2
  GalNAc-GD1a

Class: IgM
Common HIG
Polyneuropathy
Organomegaly
Endocrinopathy
M-protein
Skin changes
(POEMS)
Sensory & Motor
Symmetric
Onset: 25 to 60 yrs
NCV: Slow
Axon Loss
Target: ?

Class: IgA or IgG
90% ?
Neurofascin Sensory & Motor
Distal
Tremor
Onset: Adult
Progressive
NCV: Slow
Target
  Neurofascin

Class: IgG4
No
?
Contactin-1 Sensory & Motor
Distal or Diffuse
Onset: Adult, late
Progressive
Distal latency: Long
Conduction block
Target
  Contactin-1

Class: IgG
No Prednisone
Not HIG
* Frequency based on testing by immunofixation methodology.
Print


Chronic Immune Demyelinating Polyneuropathy (CIDP)

Clinical features
  Associated disorders
Comparative features
Laboratory features
Pathology
Treatments
Variants

  • Serum CK: High in 27% 48
  • Chemokines & Cytokines: Serum levels 45
  • CSF
  • MRI
  • Rule-out
  • Pathology: Nerve biopsy not necessary for diagnosis
  • Treatment

    Chronic Immune Demyelinating Neuropathies: Variants

    β-Tubulin Ab
    Childhood
    CIDP
    CIDP + CNS features
    Contactin-1 Ab
    Diabetes
    IgM vs GM2 & GalNAc-GD1a
    Motor
      CIDP
      MMN
      Polyradiculopathy
    Multifocal
      Upper limb
      M-protein
      IgM
      IgG or IgA
    Neurofascin Ab
    Onset
      Acute
      Subacute
    Perineuritis
    POEMS
    Sensory
      CIDP
      Polyradiculopathy


    Multifocal Motor Neuropathy (MMN) & Immune Motor Neuropathies (IMN) 3,14

    Antibodies
    Clinical
    Electrodiagnostic
    Epidemiology
    Laboratory
    Pathology
    Treatment
    Variants & DDx


    MMN: Focal weakness
      Variable finger extension

    MMN: Median nerve conduction block
      Weakness of thenar eminence
      No atrophy

    Neuropathy with IgM binding to Myelin-Associated Glycoprotein (MAG)


    GALOP syndrome 5


    POEMS Syndrome 21

    General
    Laboratory
    Nosology
    Polyneuropathy
      Pathology
    Systemic
      Edema
      Endocrine
      Organomegaly
    Treatment


    From M. Al-Lozi
      Thickened, dry skin
      Clubbing of fingers
    Major diagnostic criteria: 3 needed
    Mandatory
      Polyneuropathy
      Monoclonal plasmaproliferative disorder (Usually λ)
    Other
    Vascular endothelial growth factor (VEGF): High
    Sclerotic bone lesions
    Castelman’s disease
    Minor diagnostic criteria: 1 needed
    Organomegaly
      Spleen, Liver; Lymph nodes
    Edema
      Edema, Pleural effusion, or Ascites
    Endocrinopathy
      Adrenal, Thyroid, Pituitary, Gonadal, Parathyroid, Pancreas
    Skin Δ
      Pigmentation, Hypertrichosis, Plethora, Hemangiomata, Nail Δ


    Neuropathy with IgM binding to Sulfatide


    Demyelinating ataxic neuropathy with IgM binding to GalNAc-GD1a and GM2 gangliosides 10


    Neuropathies (Chronic) with IgM binding to GD1a, GM3 & GT1b gangliosides


    Osteosclerotic Myeloma


    Antibody testing is performed at:

    NEUROMUSCULAR CLINICAL LABORATORY: Washington University
    Box 8111 - Neurology
    660 South Euclid Avenue
    St. Louis, MO 63110
    Phone: 314-362-6981
    Fax: 314-362-2826
    e-mail: pestronka@neuro.wustl.edu


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    Chemical figures by G. Lopate.

    9/18/2018