Chronic Inflammatory Demyelinating Polyradiculoneuropathy, CIDP https://www.youtube.com/watch?v=Ys-Zw6MnZUo&t=1654s

1. By
Dr Mohammud Ibraheem

2. 1) WHAT IS CIDP?
2) EPIDEMIOLOGY
3) NEUROPATHOLOGY OF CIDP
4) CLINICALTYPES
I. TypicalCIDP
II. Atypical CIDP
1. Asymmetric sensorimotor
2. Sensory-predominant
3. Distal acquired demyelinating symmetric neuropathy
4. Proximal polyradiculopathy
5. Pure motor
6. Neurofascin antibody-mediated
7. Contactin 1 antibody-mediated

3. Chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP) is a chronically
progressive or relapsing symmetric
sensorimotor disorder with cytoalbuminologic
dissociation and interstitial and perivascular
endoneurial infiltration by lymphocytes and
macrophages.

4. The prevalence of CIDP ranges from 0.7 to 10.3
cases per 100,000 people.
There is a male predominance, with a gender
rate ratio ranging from 1.5 to 4.
CIDP primarily affects adults and the incidence
rises with advancing age.
Up to 16% of patients have an acute GBS-like
presentation.

5. the execute cause of CIDP and its variants is unknown
Immunologic basis
immunologically mediated is the strongest theory. The
cellular and humoral components of the adaptive
immune system are involved in the pathogenesis of CIDP
and its variants.
I. Cellular immunity, crossing of the blood-nerve
barrier by activated T cells, and expression of
cytokines, tumor necrosis factor, interferons, and
interleukins.
II. Humoral immunity; immunoglobulin (Ig) and
complement deposition on myelinated nerve fibers.

6. The characteristic pathologic features of CIDP
include segmental demyelination and
remyelination of peripheral nerves, resulting in
onion bulb formation
The affected nerve fibers are enlarged due to
whorls of overlapping and proliferating
Schwann cell processes encircling bare axons.

7. Nerve involvement is patchy, with unequal
involvement over the length of a nerve.
Demyelination occurs paranodally with varying
degrees of interstitial edema and endoneurial
inflammatory cell infiltrates, including
lymphocytes and macrophages. The macrophages
initiate the demyelination by unraveling and
degrading myelin. macrophages are not prominent
on most biobsys.
There is some degree of axonal degeneration. The
mechanism is not known but may be a secondary
the products of the inflammatory demyelination.

8. 10% are positive to autoantibodies against
nodal and paranodal proteins and are
considered to be pathogenic.
The majority are IgG4 subclass antibodies
directed at proteins at or near the node of
Ranvier, including neurofascin isoforms and
contactin 1 (CNTN1).
The pathogenesis of the neuropathy in these
patients is distinct from classic CIDP

9. Specific targets described in CIDP:
1) Neurofascin (NF) 155, a paranodal protein expressed
by glial cells.
2) NF140 and NF186, neuronal proteins present at
nodes and axon initial segments.
3) CNTN1 and contactin-associated protein 1 (CASPR1)
They are structural elements of the paranodal loop
attachment to the axolemma. The antibodies target
paranodal proteins and disrupt the axonal-glial junctions,
causing nerve conduction slowing.
Biopsies have not shown findings typical for CIDP, as
onion bulb formation and macrophage-mediated
demyelination.
Clinical phenotypes appear different from typical CIDP

11. • 50%-60% of all cases of CIDP.
• It is symmetric sensorimotor polyneuropathy
with proximal and distal motor involvement that
exceeds sensory involvement.
• The presentation is gradually progressive over
several months. Some patients present with
more rapidly progressive symptoms, resembling
AIDP and which have been termed "acute-onset
CIDP“.
• A relapsing-remitting course is in 1/3 and more
common in younger patients

12. Weakness is of a non-length-dependent pattern,
affecting both proximal and distal muscles in
similar degrees. This pattern is a hallmark of
an acquired demyelinating polyneuropathy
and is related to nerve root involvement
score Discretion
5 Normal strength
4 Moves joint against resistance but examiner can overcome the action
3 Moves part full range against gravity but not against any resistance
2 Moves part only when positioned to eliminate gravity
1 Only a flicker of contraction of muscle but cannot move joint
0 Complete paralysis

13. Proximal muscle weakness causes difficulty
climbing or descending stairs, rising from a
seated position, and lifting objects overhead.
Patients may have trouble walking and report
frequent falls.
Signs and symptoms of distal muscle weakness
include scuffing or tripping over the feet due to
"foot drop," difficulty with fine motor tasks like
buttoning, and difficulty opening doors or jars.

14. • Sensory impairment is greater for vibration and
position sense than for pain and temperature,
reflecting the involvement of larger myelinated
fibers.
• This causing gait ataxia because of impairment
of proprioception (sensory ataxia) and can be
mistaken for posterior column spinal cord
involvement. Unlike motor involvement, sensory
involvement tends to be worse distally, with
finger involvement frequently seen as early as
toe and foot involvement.
• Painful dysesthesias can occur.

15. Symptoms of lumbar spinal stenosis and cauda equina
syndrome occur rarely if there is marked nerve root
hypertrophy, and these may require surgical
intervention.
Cranial nerve and bulbar involvement occur in 10%-20%
of patients.
 CN VII affection, with paralysis of both upper and
lower facial muscles. Diplopia can occur with the
involvement of CN III, IV, or VI. Rarely, bulbar muscles
(eg, palate, tongue) can be affected.
 Papilledema with pseudotumor cerebri syndrome
occure rarely and are due to a very high CSF protein
level (usually >1000 mg/mL).

16. • Tremor has been reported as a common
symptom in several studies
• Autonomic involvement in typical CIDP is mild
and limited in distribution. Constipation and
urinary retention occur in more severe cases.
• The presence of prominent sensory signs and
the absence of autonomic dysfunction, facial
weakness, preceding infectious illness, or
respiratory failure are findings that raise
suspicion for acutely presenting CIDP.

17. The boundaries of these variants are not always
clearly defined .
A. Asymmetric sensorimotor
B. Sensory-predominant
C. Distal acquired demyelinating symmetric
neuropathy
D. Proximal polyradiculopathy
E. Pure motor
F. Neurofascin antibody-mediated
G. Contactin 1 antibody-mediated

18. The variants of chronic inflammatory
demyelinating polyneuropathy (CIDP) differ:
A. In the clinical presentation
B. Pathological findings
C. Electrophysiological characteristics
D. Response to immunosuppressive agents

19. The Lewis-Sumner syndrome, also known as
multifocal acquired demyelinating sensory and
motor neuropathy (MADSAM), it accounts for 5%-
10% of CIDP cases.
The presentation is strikingly asymmetric,
multifocal picture, indistinguishable from other
forms of mononeuropathy multiplex, resulting in
sensory and/or motor signs and symptoms in
individual nerve distributions.
Some patients may have autonomic symptoms,
neuropathic pain, and cranial nerve involvement.

20. It is characterized clinically by with large fiber
sensory dysfunction, including balance problems,
pain, paresthesias, and dysesthesias. Symptom
start anywhere in the body except in a length-
dependent fashion (which would be more
consistent with the distal variant).
Weakness and autonomic dysfunction are not seen.
Despite the lack of weakness, NCS may
demonstrate significant motor demyelinating
features.

21. DADS is a distal and sensory-predominant variant,
it is more slowly progressive than typical CIDP.
Patients typically present with length-dependent,
symmetric sensory or sensorimotor dysfunction in
the lower extremities with sparing of proximal
limbs, trunk, and face. Involvement of the upper
limbs may occur later (eg, more than one year after
disease onset).
Additional features in some patients include ataxia,
neuropathic pain.

22. In DADS; there is higher rate of monoclonal gammopathy,
and 50% of those with monoclonal IgM have anti-myelin-
associated glycoprotein (anti-MAG) antibodies. With further
hematologic evaluation, these patients are classified as
having monoclonal gammopathy of clinical significance
(MGCS) or Waldenström macroglobulinemia, which differs
from CIDP. Therefore, DADS with monoclonal IgM,
particularly when associated with anti-MAG, is distinct from
CIDP and tends to be resistant to the standard
immunomodulatory therapies for CIDP.
DADS without monoclonal IgM is generally considered to be a
variant of CIDP because it may respond to treatment with
immunomodulatory therapies

23. It affects the dorsal nerve roots "chronic immune sensory
polyradiculopathy" (CISP).
Clinically: symmetric sensory ataxia with marked vibration
and proprioceptive deficits.
Because the disease process spares peripheral nerve myelin
distal to the nerve roots, sensory and motor nerve
conduction studies are normal, and additional studies are
crucial to making the diagnosis.
Evidence of dorsal nerve root involvement is demonstrated
by enlarged and enhancing nerve roots on MRI, abnormal
somatosensory evoked potentials (SSEPs), and CSF protein.
A variant in which both sensory and motor nerve roots is
closely related to CISP, termed "chronic immune
sensorimotor polyradiculopathy" (CISMP)

24. It is reported in a small number of cases.
Involvement of motor nerves and sparing of
sensory fibers is present on clinical and
electrodiagnostic evaluations. Weakness is
symmetric and involve any part of the body,
including motor cranial nerves.
This is a very rare variant and must be distinguished
from lower motor neuron-predominant
amyotrophic lateral sclerosis and multifocal
motor neuropathy (in which the motor nerve
involvement tends to be more focal).

25. Patients with autoantibodies to NF155 appear
to be younger and more likely to have sensory
ataxia and prominent tremor compared with
those with antibody-negative CIDP. The
symptoms can cause severe dysfunction.
very high CSF protein levels, and poor response
to IV immunoglobulin (IVIg).
Anti-NF155 antibody-positive CIDP is unique
because of the high frequency of subclinical
demyelinating lesions in the CNS.

26. In a series of 5 patients with autoantibodies targeting
NF140 and NF186, 4 patients presented with subacute
sensory ataxia, and nerve conduction studies were
consistent with a demyelinating neuropathy. Associated
conditions included nephrotic syndrome in 2 patients and
IgG4-related retroperitoneal fibrosis in 1 patient
(Delmont E, et al 2017).
As IgG4 antibodies, neurofascin autoantibodies do not
activate complement. Similar to other IgG4 disorders (eg,
anti-muscle-specific tyrosine kinase [anti-MuSK]
myasthenia gravis), these patients do not typically
respond to IVIG but can be responsive to B cell depletion
therapy (eg, rituximab)

27. Autoantibodies of the IgG4 class to contactin 1
(CNTN1) or contactin-associated protein 1
(CASPR1) are in a small percent.
The clinical phenotype is characterized by severe
and predominantly motor with early axonal
involvement, some cases are of advanced age
As with neurofascin antibody-mediated CIDP, this
condition is also due to an IgG4 antibody and may
be responsive to B cell depletion therapy (eg,
rituximab) and refractory to IVIG.