Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic inflammatory neuropathy. CIDP is diagnosed according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria
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4. CIDP should be considered in patients presenting
with a progressive or relapsing-remitting
polyneuropathy involving both motor and sensory
nerves along with areflexia, particularly when
weakness predominates and affects proximal and
distal muscles simultaneously and symmetrically.
The diagnosis can be more difficult in patients
presenting with atypical CIDP variants
5. The age of onset is younger (mean 29 years) in
those who had a relapsing course than in those
experiencing a chronic progressive course (mean
51 years).
A history of preceding infection is found in less
than 10%.
The clinical features that distinguish CIDP from
axonal peripheral neuropathies are the prominence
of muscle weakness and the early involvement of
upper extremity and proximal muscles as well as
distal muscles.
6. Axonal polyneuropathies are characterized by
predominantly distal weakness, deep tendon
reflexes are globally reduced or absent in CIDP,
whereas only the ankle reflexes are diminished in
typical axonal polyneuropathies.
The features of CIDP point to the multifocal or
generalized nature of the disease even at early
stages of the illness.
Children have a more precipitous onset and more
prominent gait abnormalities
Pregnancy is associated with relapses, occurring
mainly in the 3rd trimester and postpartum period
7. Additional findings are
1. Postural tremor of the hands,
2. Enlargement of peripheral nerves,
3. Papilledema and facial or bulbar weakness.
4. Rarely, respiratory failure requiring mechanical
ventilation or autonomic dysfunction
5. Massive nerve root enlargement, causing
myelopathy or symptomatic lumbar stenosis
6. CIDP may be associated with a relapsing
multifocal demyelinating CNS disorder
resembling MS with CNS demyelination
8. Elements that raise suspicion for an alternative
diagnosis include:
1. The presence of weakness in the respiratory
muscles.
2. Clear asymmetric pattern of weakness.
3. Severe tremor, ataxia, or muscle weakness at
disease onset
4. Prominent autonomic dysfunction
5. Prominent pain
6. No improvement after one or more effective
therapies (eg, glucocorticoids, IVIG)
9. CIDP is a syndrome with many underlying causes.
1) CIDP is more than 10 times more frequent in
patients with IDDM and NIDDM,
2) HIV-1 infection, Chronic active hepatitis,
3) SLE, Inflammatory bowel disease.
4) Monoclonal gammopathy of undetermined
significance (MGUS),
5) Hematological malignancies (including
Waldenström macroglobulinemia [WM], multiple
myeloma, POEMS syndrome, and Castleman
disease)
6) Lymphomas
7) Melanoma or after therapy by vaccination with
melanoma
10. CIDP may occasionally be drug induced.
1. Tacrolimus,
2. Macrolide antibiotic
3. TNF-α antagonists, including etanercept,
infliximab, and adalimumab
4. Interferon-alpha
The neuropathic manifestations in these patients
may start as early as 2weeks after initiation of
therapy or as late as 16months
12. Electrodiagnostic testing
Electrophysiologic features of CIDP are those of
peripheral nerve demyelination:
1. Partial conduction block (drop in CMAP
amplitude or area of more than 20%)
2. Conduction velocity slowing
3. Prolonged distal motor latencies
4. Delay or disappearance of F waves
5. Temporal dispersion (increase in the CMAP
duration of more than 15%); suggest an
acquired process.
13.
14. Needle EMG is consistent with polyradiculopathy
pattern with fibrillation potentials and large MUAPs
with reduced recruitment involving multiple
myotomes with or without involvement of the
paraspinal muscles
15. It is difficult to determine conduction slowing in
patients who have severe axonal loss.
Evaluating nerves that supply more proximal and
less severely denervated muscles is helpful in
finding the conduction abnormalities.
Extensive studies of the 4limbs improve the
electrodiagnostic yield.
Cranial nerve conduction studies; showing
conduction slowing is useful for diagnosis.
16. Distal acquired demyelinating symmetric
neuropathy; NCS showed symmetrical and
uniform slowing of distal latencies more than
conduction velocities with rare conduction
blocks.
MADSAM (multifocal asymmetric
demyelinating sensory and motor) neuropathy;
NCS demonstrating focal conduction block or
severe slowing of nerve conduction.
Sensory nerve root involvement is suggested by
abnormal somatosensory evoked responses,
17. Electrodiagnostic criteria for CIDP
These criteria are applied by testing the median,
ulnar (stimulated below the elbow), peroneal
(stimulated below the fibular head), and tibial
nerves on one side of the body.
During testing, limb temperature should be no
less than 33°C at the palm and no less than 30°C
at the external malleous
18. Definite CIDP
At least one of the following:
1. MDL prolongation ≥50% above ULN in 2nerves,
2. Reduction of MCV ≥30% below LLN in 2nerves,
3. Prolongation of F-wave latency ≥20% above ULN
in 2nerves (≥50% if amplitude of distal negative
peak CMAP <80% of LLN),
4. Absence of F-waves in 2nerves (if these nerves
have distal negative peak CMAP amplitudes ≥20%
of LLN) + ≥1 other demyelinating parameter in ≥1
other nerve,
19. 5. MCB: ≥30% reduction of the proximal relative to
distal negative peak CMAP amplitude, excluding
the tibial nerve, and distal negative peak CMAP
amplitude ≥20% of LLN in 2nerves; or in 1nerve
+ ≥ 1 other demyelinating parameter except
absence of F-waves in ≥1 other nerve,
6. Abnormal temporal dispersion: >30% duration
increase between the proximal and distal negative
peak CMAP (at least 100% in the tibial nerve) in
≥2 nerves,
7. Distal CMAP duration (interval between onset of
the 1st negative peak and return to baseline of the
last negative peak) prolongation in ≥1 nerve + ≥1
other demyelinating parameter in ≥1 other nerve
20. Probable CIDP
≥30% amplitude reduction of the proximal
negative peak CMAP relative to the distal,
excluding posterior tibial nerve, if the distal
negative peak CMAP is ≥20% of LLN, in two
nerves plus at least one other demyelinating
parameter (meeting any of the definite criteria)
one other nerve
Possible CIDP
As in 'Definite CIDP but in only one nerve
21. Laboratory studies
1. Fasting serum glucose and/or oral glucose
tolerance test, HbA1c
2. CBC, LFT, TFT, Serum calcium and creatinine
3. Serum protein electrophoresis (SPEP) and
Immunofixation
4. Serum free light chain (FLC) assay, or 24-hour
urine protein electrophoresis (UPEP) and
Immunofixation
5. CRP, ANAS, Angiotensin-converting enzyme
22. Laboratory studies
7. Hepatitis panel, HIV antibody, Borrelia burgdorferi
serology
8. Chest radiograph
9. Skeletal survey and vascular endothelial growth
factor (VEGF) if a monoclonal gammopathy is
found
10.Evaluation for inherited neuropathies as CMT or
transthyretin (TTR) familial amyloid
polyneuropathy (FAP)
11.Testing for anti-MAG is recommended if an IgM
gamopatny is identified. Neurofascin and contactin 1
(CNTN1) antibody testing
23. Lumbar puncture
CSF analysis is recommended in patients with
suspected CIDP particularly in whom the clinical and
electrophysiologic findings are inconclusive.
CSF protein is elevated (45 mg/dLl and WBC is
normal) in over 80%. An elevated CSF protein level
in patients with DM should be attributed to CIDP if
>100mg/dl.
24. Lumbar puncture
An increased CSF WBC of >10 cells/mm³ should
suggest a diagnosis other than CIDP as infection,
inflammation or neoplasm. An exception to this
general rule is that patients with HIV infection may
have pleocytosis, although the CSF WBC count in
patients with CIDP and HIV infection is generally
<50/mm²
25. Neuroimaging
MRI with gadolinium of the spinal cord, spinal
roots, cauda equina, brachial plexus, lumbosacral
plexus, and other nerve to look for enlarged or
enhancing nerves.
MRI is usually reserved for atypical cases, often
when clinical and electrophysiologic findings are
focal (as multifocal CIDP), and to rule out other
causes of neuropathy and infiltrative pathology.
26. Neuroimaging
MRI is important if chronic immune sensory
polyradiculopathy (CISP) or chronic immune
sensorimotor polyradiculopathy (CISMP) are being
considered, as these are rare variants with clinical
features that overlap with structural. infectious, and
infiltrative causes of polyradiculopathy.
In brachial plexus MRI, nerve enlargement or
enhancement is seen in approximately 40%-30% of
patients with CIDP.
27.
28. (A)T2 showing lack of regular fluid-isointense signal, due to
swollen cauda equina fibers (arrows).
(B)T1, Diffuse cauda equina enhancement (arrows) is
depicted, indicating inflammation.
(C)T1, Enlarged and enhancing root fibers are shown, exiting
the neuroforamen (arrows).
29. Nerve ultrasound
When appropriate expertise is available,
neuromuscular ultrasound can also be used to
detect nerve hypertrophy in patients with
acquired and hereditary forms of chronic
demyelinating neuropathies. Although the
findings are not specific for CIDP, they may help
indicate regions of involvement
30. Median nerve
A, Cross-sectional area of the median nerve measuring 8 mm
B, Cross-sectional image at 7 cm proximal to the antecubital fossa,
measuring 21 mm.
C, Longitudinal image demonstrating focal enlargement and
hypoechogenicity.
31. Nerve biopsy
Typically, the sural nerve is biopsied, but other
nerves include the superficial peroneal, superficial
radial, and gracilis motor nerve.
Limitation of nerve biopsy is suboptimal sensitivity
and specificity. CIDP is a multifocal disorder, and
motor nerve fibers tend to be more affected than
sensory nerves, the inflammatory component of
CIDP may not be prominent and thus may not be
apparent on biopsy.
32. Nerve biopsy
Nerve biopsy can provide solid evidence of
demyelination. In addition biopsy reveals other
neuropathies that mimic CIDP, as those due to
amyloidosis, sarcoidosis and vasculitis .
Electron microscopy and teased fiber analysis of
nerve biopsy specimens is highly desirable
34. AIDP
There is a temporal continuum between AIDP and
CIDP. The time course of progression and the
occurrence of relapses are used to distinguish
between these entities:
GBS commonly reaches its nadir within 3-4 weeks
but does not progress beyond 8 weeks.
CIDP continues to progress or has relapses for
greater than 8weeks.
35. AIDP
Subacute inflammatory demyelinating
polyneuropathy (SIDP) is the term used by some
authors for disease that reaches its nadir between
4-8weeks.
GBS is typically monophasic, but up to two
relapses in the first 8weeks from onset can occur.
3 or more relapses in the first 8weeks is highly
suggestive of acute CIDP. Relapses closer to the
eight-week time period is more suggestive of
CIDP.
36. AIDP
Observation of the patient over time can clarify
whether the clinical course is that of AIDP or
CIDP, and therapeutic interventions are likely to
be initiated before a patient reaches a specific
time point that distinguishes between these
entities. As an example, some patients with CIDP
have a subacute onset resembling that seen in
GBS, and CIDP is recognized only after relapses
or progression occur over the ensuing few
months.
37. AIDP
Clinical features that distinguish AIDP from CIDP.
1. The onset of GBS is usually easily identified,
while the onset of CIDP is typically less clear.
2. Antecedent events are more frequent with GBS
than in CIDP. 70% of AIDP cases are preceded by
an infectious illness, vaccination, or surgery by 3-
4 weeks prior to the onset of clinical symptoms.
The antecedent event prior to CIDP in no more
than 30%
38. AIDP
3. Prominent sensory signs (ie, sensory ataxia
and impaired vibration and pinprick
sensation).
4. Cranial nerve involvement is more common
in GBS.
5. The need for ventilator support favors GBS .
6. Autonomic involvement in the form of labile
hypertension, heart rhythm disorders, and
gastrointestinal dysmotility also favors GBS.
39. Chronic demyelinating neuropathies
There are several forms of chronic demyelinating
neuropayhies are distinct from CIDP on the basis of
clinical, electrodiagnostic, and therapeutic
differences. These include:
1) Multifocal motor neuropathy (MMN).
2) Distal acquired demyelinating symmetric
neuropathy (DADS) with monoclonal IgM
gammopathy and anti-myelin-associated
glycoprotein antibodies (anti-MAG).
40. Chronic demyelinating neuropathies
3. IgM-associated demyelinating neuropathies as
CANOMAD (chronic ataxic neuropathy with
ophthalmoplegia, IgM paraprotein, cold
agglutinins, and disialosyl antibodies).
CANOMAD is a chronic disorder with clinical
features similar to the Miller Fisher variant of
GBS. In CANOMAD, the GQ1b antibody is an
IgM antibody; in Miller Fisher syndrome, it is an
IgG antibody. Other IgM antibodies associated
with neuropathy include GD1a and GD1b, both
of which tend to cause a sensory-predominant
disorder.
41. Chronic demyelinating neuropathies
4) POEMS syndrome (osteosclerotic myeloma:
Polyneuropathy, Organomegaly, Endocrinopathy,
Monoclonal protein, Skin changes).
5) Demyelinating neuropathy associated with
medications such as tumor necrosis factor-alpha
blockers and checkpoint inhibitors
42. Chronic demyelinating neuropathies
CIDP is reported in association with a variety of
systemic illnesses as Lyme disease, hepatitis B or C,
HIV infection, SLE and other collagen vascular
disorders, thyroid disease, nephrotic syndrome,
solid organ or bone marrow transplantation, and
inflammatory bowel disease. The associations are
not necessarily causative, and in some cases, the
systemic illness is associated with increased risk for
more than one type of neuropathy
43. Genetic mimics of CIDP
Certain genetic disorders of peripheral nerve myelin
have characteristics that can mimic the clinical or
electrodiagnostic features of CIDP or its variants.
These include:
1) CMT disease, particularly CMT1A, adult-onset
CMT1B, CMT1X, and recessive cases as CMT4,
can cause multifocal, nonuniform slowing and
conduction block.
2) Hereditary neuropathy with liability to pressure
palsies, which causes conduction slowing at
compression sites.
44. Genetic mimics of CIDP
3) Transthyretin (TTR) familial amyloid
polyneuropathy (FAP) due to mutations in the TTR
gene is typically axonal but occasionally can
manifest as a demyelinating polyneuropathy with
features that overlap with CIDP, particularly
sporadic, late-onset (>50 years) forms of the
disease. Clues that may alert the clinician to the
possibility of TTR-FAP include prominent pain,
dysautonomia, distal upper limb motor deficits,
extension of small fiber sensory loss above the
wrist, and absence of ataxia. Sequencing of the TTR
gene can confirm the diagnosis. This is of particular
importance as new therapies for FAP are available.
45. Genetic mimics of CIDP
A careful family history and examination of parents
and siblings are important if these disorders are a
consideration, although absence of a family history
does not rule out a genetic cause. Appropriate
genetic testing should be considered in select
patients, particularly for peripheral myelin protein
22 (PMP22) gene duplication or deletion, connexin
32, and TTR.
47. Diagnosis
The following criteria support the diagnosis of the
classic form of CIDP:
1) Progression over at least two months
2) Weakness more than sensory symptoms
3) Symmetric involvement of arms and legs
4) Proximal muscles involved along with distal
muscles
48. Diagnosis
5. Widespread reduction or loss of deep tendon
reflexes
6. CSF protein without pleocytosis
7. Nerve conduction evidence of a demyelinating
neuropathy
8. Nerve biopsy evidence of segmental demyelination
with or without inflammation
9. Gait ataxia secondary to large fiber sensory loss
There is still no gold-standard set of diagnostic criteria
for demyelination, or for the diagnosis of CIDP and its
variants
49. EFNS/PNS criteria
The EFNS/PNS guideline defines CIDP as typical or
atypical. The diagnosis of CIDP is based upon
clinical, electrodiagnostic, and supportive criteria:
A. Clinical inclusion criteria for typical CIDP
require both of the following:
I. Chronically progressive or recurrent symmetric
proximal and distal weakness and sensory
dysfunction of all extremities, developing over
at least 2months: cranial nerves may be affected
II. Absent or reduced tendon reflexes in all
extremities
50. EFNS/PNS criteria
B. Clinical inclusion criteria for atypical CIDP require one of
the following, but otherwise as in typical CIDP. tendon
reflexes may be normal in unaffected limbs:
I. Predominantly distal (distal acquired demyelinating
symmetric neuropathy [DADS]) or
II. Asymmetric (multifocal acquired demyelinating sensory
and motor neuropathy [MADSAM), Lewis-Sumner
syndrome) or
III. Focal (eg, involvement of the brachial or lumbosacral
plexus or of one or more peripheral nerves in one upper or
lower limb); or
IV. Pure motor
V. Pure sensory (including chronic immune sensory
polyradiculopathy [CISP] affecting the central process of
the primary sensory neuron)
51. EFNS/PNS criteria
C. Clinical exclusion criteria:
I. Neuropathy probably caused by B. burgdorferi infection,
diphtheria, drug or toxin exposure
II. Hereditary demyelinating neuropathy
III. Prominent sphincter disturbance
IV. Diagnosis of multifocal motor neuropathy (MMN)
V. IgM monoclonal gammopathy with high titer antibodies to
myelin-associated glycoprotein (MAG)
VI. Other causes for a demvelinating neuropathy including
POEMS svndrome. osteosderotic myeloma, and diabetic
and nondiabetic lumbosacral radiculoplexus neuropathy;
peripheral nervous system lymphoma and amyloidosis may
occasionally have demyelinating features
52. EFNS/PNS criteria
Supportive criteria:
1) Elevated CSF protein with TLC <10/mm³, MRI showing
gadolinium enhancement and/or hypertrophy of the cauda equina,
lumbosacral or cervical nerve roots, or the brachial or
lumbosacral plexuses
2) Abnormal sensory electrophysiology in at least 1nerve:
I. Normal sural with abnormal median or radial SNAP amplitudes;
or
II. Conduction velocity <80% of LLN (<705 if SNAP amplitude
<80% of LLN; or
III. Delayed SSEPs without CNS disease
3) Clinical improvement following immunomodulatory treatment
4) Nerve biopsy showing unequivocal evidence of demyelination
and/or remyelination by electron microscopy or teased fiber
analysis
53. Koski criteria
The Koski criteria require the following:
A. Chronic polyneuropathy, progressive for at least eight
weeks
B. No serum paraprotein and no genetic abnormality,
and either.
I. Recordable CMAP in at least 75% of motor nerves
and either abnormal distal latency or abnormal motor
conduction velocity or abnormal F wave latency in
>50% of motor nerves; or
II. Symmetric onset or symmetric exam and weakness
in all four limbs and proximal weakness in at least
one limb