CIDP

CIDP: Chronic Inflammatory Demyelinating Polyneuropathy
- Definition
- Pathogenesis
- Clinical Presentations
- Diagnostic criteria
- Differential Diagnosis
- Treatment

1. CIDP
Chronic Inflammatory Demyelinating
Polyneuropathy
BY: Mahmoud Magdy Elshobaky

2. INTRODUCTION
CIDP(Chronic Inflammatory Demyelinating Polyneuropathy)
It is an acquired, immune mediatedneuropathy affection
peripheral nerves and nerve roots.
Typically, characterized by a relapsing-remitting or
progressive course of symmetricweakness of proximal and
distal muscles.
Identified by electrodiagnostic and/or pathologic features
of demyelination and responsiveness to immunomodulatory
treatments.

3. EPIDEMIOLOGY
Prevalence ranges from 0.7 to 10.3cases per
100,000 *
Slightly more in males
Primarily affects adultsand the incidence rises with
advancing age.
Nospecific predisposing risk factor.
Noclear geneticpredisposition.
* BROERSMC, BUNSCHOTEN C, NIEBOERD, LINGSMAHF, JACOBS BC. INCIDENCE AND PREVALENCE OF CHRONIC INFLAMMATORY DEMYELINATING
POLYRADICULONEUROPATHY: A SYSTEMATIC REVIEW AND META -ANALYSIS. NEUROEPIDEMIOLOGY. 2019;52(3 -4):161-172. DOI: 10.1159/000494291. EPUB2019
JAN 22. PMID: 30669140; PMCID: PMC6518865.

4. PATHOGENESIS –Immunologic basis
Both Cellular and Humoral
immunity are involved.
Cellular immunity:
T cell activation, activated T cells
cross blood-nerve barrier,
expression of cytokines, tumor
necrosis factor, interferons &
interleukins
Humoral immunity:
Ig and complement deposition on
myelinated nerve fibers.

5. PATHOGENESIS –Neuropathologic
findings
Segmental demyelination and remyelination
onion bulb formation
enlarged fibers (proliferating Schwann cells encircling bare axons)
Patchyinhomogeneous involvement over the length of the nerve.
Demyelination : paranodal, near nodes of Ranvier.
Endoneurial inflammatory infiltrates : lymphocytes, macrophages ,..
Some degree of axonal degeneration (unknown mechanism)
Nodal and paranodal antibodies in 10% of patients
Auto antibodies against nodal and para nodal proteins (neurofasin [NF],
contactin1 [CNTN1])
Biopsies : No typical findings on CIDP (no onion bulb, no macrophage
mediated demyelination)

6. CLINICAL FEATURES –Typical CIDP
Most common subtype : 50-60 % -slowly progressive / relapsing remitting (1/3) -
Symmetricsensorimotor
Motor
•Proximal and distal muscle weakness
exceeds the extent of sensory loss
•Proximal muscles : difficulty climbing or
descending stairs, rising from seated
position, lifting objects.
•Distal muscles: scuffing or tripping over
the feet due to "foot drop," difficulty with
fine motor tasks like buttoning, and
difficulty opening doors or jars.
•Cranial nerve and bulbar involvement in
10-20 % of cases.
Sensory
•Less prominent –worse distally with finger
involvement (toe and foot)
•Vibration and position sense affected >pain
and temperature (involvement of large myelinated
fibers) -sensory ataxia
•Painful dysesthesia, Back pain may occur.
•Symptoms of lumbar spinal stenosis and cauda
equina syndrome : rarely , require surgical
intervention.
Autonomic
Mild and limited in distribution : constipation &
urinary retention may occur in severe cases.
Reflexes
Reduced or absent
EAN/PNS Clinical criteria for Typical CIDP
All the following:
•Progressive or relapsing, symmetric, proximal and distal muscle weakness of upper
and lower limbs, and sensory involvement of at least two limbs
•Developing over at least 8 weeks
•Absent or reduced tendon reflexes in all limbs
Van den Bergh, PYK,van Doorn, PA,Hadden, RDM, et al.European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronicinflammatory demyelinating polyradiculoneuropathy: Report of
a joint Task Force—Second revision.J PeripherNervSyst.2021;26(3):242–268.https://doi.org/10.1111/jns.12455

7. CLINICAL FEATURES –CIDP variants
Multifocal Acquired demyelinating sensory and motor neuropathy (MADSAM)
5 -10 %
Asymmetric , multifocal picture, sensory and motor.
May start in any nerve distribution.
May present with autonomic symptoms, neuropathic pain, and cranial nerve involvement.
Focal
Uncommon, sensorimotor deficits isolated to brachial or lumbosacral plexus.
Pure Motor
Very rare, motor involvement and sparing of sensory fiber present on clinical and electro
diagnostic evaluation
Pure Sensory
Distal acquired demyelinating symmetric neuropathy (DADS; distal CIDP)
Distal and sensory predominant
EAN/PNS Clinical criteria for CIDP variants
One of the following, but otherwise as in typical CIDP (tendon reflexes may be normal in unaffected
limbs):
•Distal CIDP: distal sensory loss and muscle weakness predominantly in lower limbs
•Multifocal CIDP: sensory loss and muscle weakness in a multifocal pattern, usually asymmetric,
upper limb predominant, in more than one limb
•Focal CIDP: sensory loss and muscle weakness in only one limb
•Motor CIDP: motor symptoms and signs without sensory involvement
•Sensory CIDP: sensory symptoms and signs without motor involvement
Van den Bergh, PYK,van Doorn, PA,Hadden, RDM, et al.European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronicinflammatory demyelinating polyradiculoneuropathy: Report of
a joint Task Force—Second revision.J PeripherNervSyst.2021;26(3):242–268.https://doi.org/10.1111/jns.12455

8. CLINICAL FEATURES –Other CIDP
variants ?!
Chronic immune sensory polyradiculopathy (CISP)
Proximal polyradiculopathy, consisting of inflammatory demyelination confined to dorsal
(sensory) nerve roots.
Spares peripheral nerve myelin distal to the nerve root → sensory & motor nerve conduction
studies are normal
So, consider other studies : MRI (enlarged & enhanced nerve roots), SSEPs (abnormal), CSF (↑ protein)
Present with symmetric sensory ataxia, marked vibration and proprioceptive deficits.
Chronic immune sensorimotor polyradiculopathy (CISMP)
Both sensory and motor roots are involved.
The inclusion of CISP or CISMP as variants of CIDP has been questioned by some experts
because studies have not clearly demonstrated a demyelinating pathophysiology*
Nodal and paranodal disorders (Autoimmune nodopathies).
Antibodies against nodal-paranodal cell-adhesion molecules (contactin-1 [CNTN1],
neurofascin-155 [NF155], contactin-associated protein 1 [Caspr1], and neurofascin isoforms
NF140/186)
Clinical features and conduction changes as seen in CIDP.
Not clearly demyelinating & do not respond to typical immunomodulatory treatments of CIDP
*VAN DEN BERGH, PYK,VAN DOORN, PA,HADDEN, RDM, ET AL.EUROPEAN ACADEMY OF NEUROLOGY/PERIPHERAL NERVE SOCIETY GUIDELINE ON DIAGNOSIS AND TREATMENT OF CHRONICINFLAMMATORY DEMYELINATING
POLYRADICULONEUROPATHY: REPORT OF A JOINT TASK FORCE—SECOND REVISION.J PERIPHERNERVSYST.2021;26(3):242–268.HTTPS://DOI.ORG/10.1111/JNS.12455

9. DIFFERENTIAL DIAGNOSIS
Acute inflammatory demyelinating polyneuropathy (AIDP;GBS)
*DIONNE A, NICOLLE MW, HAHN AF. CLINICAL AND ELECTROPHYSIOLOGICA L PARAMETERS DISTINGUISHING ACUTE -ONSET CHRONIC INFLAMMATORY
DEMYELINATING POLYNEUROPATHY FROM ACUTE INFLAMMATORY DEMYELINATI NG POLYNEUROPATHY. MUSCLE NERVE. 2010 FEB;41(2):202 -7. DOI:
10.1002/MUS.21480. PMID: 19882646.
AIDP CIDP
Course &
progression
Reaches its nadir 3-4 weeks.
Monophasic but may relapse (2
relapses max in the first 8 weeks).
Greater than 8 weeks.
If > 2 relapses → acute onset
CIDP.
Onset Easily identified Less clear
Antecedent
events
More: 70% of AIDP proceeded by
(infection, vaccination, surgery 3-4
weeks prior to onset)
Less then 30%
Prominent sensory signs (i.e., sensory ataxia and impaired vibration and pinprick
sensation) favor CIDP*
Cranial nerve involvement is more common in GBS.
The need for ventilator support favors GBS*
Autonomic involvement in the form of labile hypertension, heart rhythm disorders, and
gastrointestinal dysmotility also favors GBS.

10. DIFFERENTIAL DIAGNOSIS
Other chronic demyelinating neuropathies
Multifocal motor neuropathy (MMN).
Other IgM-associated demyelinating neuropathies as:
CANOMAD (chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins, and
disialosylantibodies).
POEMS syndrome (osteosclerotic myeloma: Polyneuropathy, Organomegaly,
Endocrinopathy, Monoclonal protein, Skin changes).
Demyelinating neuropathy associated with medications such as tumor necrosis
factor-alpha blockers and checkpoint inhibitors.
CIDP has been reported in association with a variety of systemic illnesses:
HCV, HBV, HIV, Lyme, SLE, IBD, thyroid disease, nephrotic syndrome..
Genetic mimics of CIDP:
Charcot-Marie-Tooth disease.
Hereditary neuropathy with liability to pressure palsies.
Transthyretin (TTR) familial amyloid polyneuropathy (FAB): typically, axonal but occasionally
demyelinating polyneuropathy.
*DIONNE A, NICOLLE MW, HAHN AF. CLINICAL AND ELECTROPHYSIOLOGICA L PARAMETERS DISTINGUISHING ACUTE -ONSET CHRONIC INFLAMMATORY
DEMYELINATING POLYNEUROPATHY FROM ACUTE INFLAMMATORY DEMYELINATI NG POLYNEUROPATHY. MUSCLE NERVE. 2010 FEB;41(2):202 -7. DOI:
10.1002/MUS.21480. PMID: 19882646.

11. DIAGNOSTIC EVALUATION
History and neurological examination
Progressive or rr–at least 8 weeks –motor and sensory –proximal and distal –symmetric –
areflexia.
Exclude CIDP if: weakness in respiratory ms, asymmetric, sever motor at onset, prominent
autonomic, prominent pain, no improvement after one or more effective therapies (e.g,
glucocorticoid, IVIG)
Electrodiagnostic testing.
Lab studies:
CBC, FBS, HBA1c, Ca, LFT, KFT, TFT, ESR, ANA, CRP, HCV, HBV
Lumbar puncture
CSF ptnin most cases > 100 and WBCs normal, +veantimyelinAbs
Nerve biopsy (sural nerve)
Demyelination and remyelination , onion bulb formation, T-lymphocyte cell infiltration.
MRI
Enlarged enhancing nerve roots, plexus and peripheral nerves.
Nerve ultrasound
Focal nerve enlargement.
Electrodiagnostic criteria for CIDP
At least one of the following demyelinating parameters are necessary:
•≥50% prolongation of motor distal latency above the ULN in two nerves
•≥30% reduction of motor conduction velocity below the LLN in two nerves
•≥20% prolongation of F-wave latency above the ULN in two nerves, or >50% if the amplitude of the
distal negative peak CMAP is <80% of the LLN
•Absence of F waves in two nerves, if these nerves have amplitudes of distal negative peak CMAPs
≥20% of the LLN, plus at least one other demyelinating parameter (meeting any of the definite
criteria) in at least one other nerve
•Partial motor conduction block, defined by a ≥30% amplitude reduction of the proximal negative
peak CMAP relative to distal, if distal negative peak CMAP is ≥20% of the LLN, in two nerves, or in
one nerve plus at least one other demyelinating parameter (meeting any of the definite criteria) in at
least one other nerve
•Abnormal temporal dispersion, defined by a >30% duration increase between the proximal and
distal negative peak CMAP in at least two nerves
Possible CIDP
As in "CIDP" but in only one nerve

12. TREATMENT
Goals and course of treatment
To stop immune attack against the myelin sheath of peripheral nerves so that secondary
axonal degeneration is minimized
The treatment approach depends on the severity and course of disease:
Mild disease with minimal impact on function and quality of life → TTT may not be required.
Most patients are significantly impaired and need treatment.
Multiple medications may be required to optimize response.
Serial clinical examinations are used to monitor for relapse and guide changes in therapy.
Initial Therapy
Initial immune modulatory treatment using either IVIG, plasma exchangeor glucocorticoids.
Initial choice among these therapies is influenced by disease severity, concurrent illness,
venous access, treatment side effects, availability, and cost.
Patients with related chronic immune-mediated neuropathies due to nodal or paranodal
antibodies (e.g., neurofascin, contactin, may be unresponsiveto typical initial therapies → can
be responsive to B cell depletion therapy (e.g., rituximab)

13. TREATMENT –Intravenous immune globulin
IVIG is usually easierto administer than plasma exchange and may have
a more rapid responsefor disability improvement than with
glucocorticoids.
Dosing regimens
Initial dose is 2g/kginfused over 4-5 days(e.g., 0.4 g/kg per day for 5
days).
Repeat infusion of IVIG (1g/kg) every 3 weeks for 2-3 months before
determining efficacy.
For patients who respond well to therapy, the treatment can be tapered
once improvement plateaus.
Adverse effects
Most common: transient headache, nausea, and fever.
Other: aseptic meningitis, rash, acute renal failure, and rarely hyper
viscosity and thrombosis.
Contraindicated with Immunoglobulin A (IgA)-deficient patients since it
can lead to anaphylaxis.

14. TREATMENT –Plasma exchange
Effective alternative to IVIG; however, less convenient, invasiveprocedure, available only at
specialized centers.
Dosing regimens
4 to 6 exchanges over 8 to 10 days
Then 1 exchange every 3 to 4 weeks according to clinical response.
Adverse effects
Hypotension, sepsis, and problems with intravenous access.
Requires repeated venous access and (often) indwelling cathetersthat are susceptible to
clotting and infection

15. TREATMENT –Glucocorticoids
Initial treatment in patients with more insidious CIDP ( a rapid treatment response is
less critical)
Dosing schedule
Pulse-dose glucocorticoids:
IV methylprednisolone (1000 mg/day) for 3 days followed by 1000 mg one day a week for 4 weeks.
Or oraldexamethasone40 mg for four consecutive days once a month.
Or oral prednisone 600 mg once a week.
Taper the dose or frequency if improvement or clinical stabilization occurs.
If intolerable adverse effects, taper or switch agent.
Daily dose glucocorticoid:
Prednisone 1 to 1.5 mg/kg daily (no more than 100mg)
Alternate-day glucocorticoid: less side effects but less effective.
Adverse effects
Weight gain, cushingoid appearance, easy bruising and skin fragility, cataracts, aseptic necrosis of the femoral or
humoral heads, hypertension, diabetes and osteoporosis
Contraindications
Peptic ulcer disease, brittle diabetes, refractory hypertension, severe osteoporosis and systemic fungal infection.

16. TREATMENT –Specific treatment options
Maintenance IVIG
Dose: 1g/kg over 1 to 2 days every 3 weeks.
If clinically stable → taper maintenance as low as 0.4g/kg per dose.
If neuropathy worsens → increase maintenance dose up to 2g/kg.
Subcutaneous immune globulin (SCIG)
An alternative to maintenance IVIG
May be better tolerated than IVIG with a reduction in adverse effects.
Maintenance glucocorticoids
Patients who have a good response can begin dose tapering after one to three months.
Tapering can be done as a daily or every-other-day regimen or by pulsed oral steroids
e.g., begin with 80 mg prednisone alternating with 60 mg for 1 month → 80 mg alternating with 40 for 1
month → 80mg alternating with 0 mg → taper every-other-day daily dose by 10 mg each month until 30
mg → taper by 5.
If symptoms recur during the taper → go back up to a higher dose by at least 10 to 20 mg
IV weekly pulse (methylprednisolone 0.5g once a week ) is an effective option for long term
treatment.
Taper by decreasing frequency to once every 2 to 12 weeks.

17. TREATMENT –Patients with refractory disease
Cyclosporine
Appeared effective in one case series.
Keep plasma level between 100 and 150 ng/ml.
Greater side effect profile than other agents.
Methotrexate
At least 4-month trial if the clinical condition allows.
Patients should receive folic acid 1mg daily to prevent hematologic and other side effects.
Rituximab
Appears to be effective in refractory CIDP and CIDP patients associated with IgG4 antibodies to
neurofascin and contactin
Cyclophosphamide
Pulse IV can be effective in patients with sever refractory disease and can lead to long term
remission.
Dose: 1000 mg/m
2
infused monthly.
Has potentially life-threatening side effects.
Autologous hematopoietic stem cell transplantation (AHSCT)
Last resort

18. PROGNOSIS
The prognosis of CIDP is generally favorable, but data are
limited.
Approximately 30 percent of patients achieve cure or
remission, while approximately 18 percent have unstable
active disease with a progressive or relapsing course.*
* GORSONKC, VAN SCHAIK IN, MERKIESIS, ET AL. CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY DISEASE ACTIVITY
STATUS: RECOMMENDATIONS FOR CLINICAL RESEARCH STANDARDS AND USE IN CLINICAL PRACTICE. J PERIPHERNERVSYST 2010; 15:326.

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