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CHRONIC IMMUNE POLYNEUROPATHIES: DEMYELINATING

Demyelinating PN
  Comparative features
  Treatment strategies

CIDP
  Clinical features
  Laboratory features
  Pathology
  Treatments
  Variants
Contactin-1
GALOP syndrome
GD1a antibody
  Motor-Sensory neuropathy
Multifocal motor neuropathy
MAG antibody associated neuropathy
Neurofascin 155 antibody
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 or
  Relapsing
Motor + Sensory change
Slow NCV
Conduction Block
Distal Latency: Long
Slow F-waves
Targets
  β-tubulin
  Heparan sulfate

Class: IgM or IgG

Frequency: 20%
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 change
Slow NCV
Conduction Block
Distal Latency: Long
Slow F-waves
? ? 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
  Axonal Loss

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
Slow NCV
No conduction block
Axonal Loss
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
Slow NCV
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
Slow NCV
Axonal Loss
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
Slow NCV
Targets
  GM2
  GalNAc-GD1a

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

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

Class: IgG4
No
?
Contactin-1 Sensory & Motor
Distal or Diffuse
Onset: Adult, late
Progressive
Long DL
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
Comparative features
Laboratory features
Pathology
Treatments
Variants



Chronic Immune Demyelinating Neuropathies: Variants

β-Tubulin antibodies
Childhood
CIDP
CIDP + CNS features
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
Major diagnostic criteria: 3 needed
Polyneuropathy (Mandatory)
Monoclonal plasmaproliferative disorder (Mandatory)
Vascular endothelial growth factor (VEGF) levels: High in serum or plasma
Sclerotic bone lesions
Castelman’s disease
Minor diagnostic criteria: 1 needed
Organomegaly (Splenomegaly, Hepatomegaly or Lymphadenopathy)
Edema (Edema, Pleural effusion, or Ascites)
Endocrinopathy (Adrenal, Thyroid, Pituitary, Gonadal, Parathyroid, Pancreatic)
Skin changes (Hyperpigmentation, Hypertrichosis, Plethora, Hemangiomata, White nails)


Neuropathy with IgM binding to Sulfatide


Demyelinating ataxic neuropathy with IgM binding to GalNAc-GD1a and GM2 gangliosides10


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.

10/16/2014