1. The document discusses various variants of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). It describes clinical features and electrodiagnostic patterns of AIDP subtypes including AMAN and AMSAN as well as regional and atypical variants of GBS like Miller Fisher Syndrome. 2. Rare autoimmune nodopathies caused by antibodies targeting nodes of Ranvier are described. Clinical features associated with antibodies to contactin-1, neurofascin 155, neurofascin isoforms and contactin-associated protein 1 are summarized. 3. Diagnostic criteria and variants of CIDP

1. Variants of
AIDP & CIDP
Dr Zuber Ali Quazi
Senior Resident
Neurology

2. Introduction
– Inflammatory demyelinating polyradiculoneuropathies are
acquired immunologically mediated polyneuropathies
– Classified on the basis on their clinical course into two major
groups:
(1) GBS, and (2) CIDP.
– GBS = the maximal deficits develop over days or weeks (max 4
weeks), f/b a plateau phase and gradual recovery.
– CIDP = Either a slowly progressive ( ≥ 2 months) or a Relapsing-
Remitting course.

3. AIDP Patterns
30–40% 5–15% 5–10% <5% <5% <1% 5–25% <5%

4. AIDP Types
– Common Subtypes
– Acute Inflammatory
Demyelinating
Polyradiculoneuropathy (AIDP)
– Acute Motor Axonal Neuropathy
(AMAN)
– Acute Motor-sensory Axonal
Neuropathy (AMSAN)
– Rare Variants
– Miller-fisher Syndrome
– Ataxic variant (Acute Ataxic Neuropathy)
– Pharyngeal-cervical-brachial variant
– Multiple Cranial Neuropathy Variant
– Facial Diplegia With Paresthesias
– Paraparetic Variant
– Acute Pandysautonomia

5. AMSAN
– Acute & Rapidly Progressive course; Max deficit in <7 days.
– Profound Quadriparesis; severe muscle wasting and
– Prolonged ventilatory support.
– Poor prognosis for recovery.
– NCV- Reduced / Absent CMAPs, Absent SNAPs. without
significant conduction slowing, and

6. AMAN
– 1st reported in Northern China (Summer); “Chinese
Paralysis”
– The most common GBS subtype in Asia.
– Campylobacter jejuni infection (76% of AMAN); Anti-GM1
or Anti-GD1a
– NCV - Normal SNAPs; Reduced CMAP.

7. Anti- GQ1b Syndromes
Miller Fisher syndrome (MFS);
Bickerstaff Brainstem Encephalitis (BBE);
Pharyngeal-cervical-brachial Variant

8. Nortina Shahrizaila, and Nobuhiro Yuki J Neurol Neurosurg Psychiatry 2013;84:576-583

9. Fisher–Bickerstaff syndrome
 Fisher syndrome
 Incomplete forms:-
• Acute ophthalmoparesis (without ataxia)
• Acute Ptosis
• Acute Mydriasis
• Acute Oropharyngeal Palsy
• Acute Ataxic Neuropathy (without ophthalmoplegia)
o Ataxic Guillain–Barré syndrome
o Acute Sensory Ataxic Neuropathy
 Bickerstaff Brainstem Encephalitis
Pharyngeal-cervical-brachial weakness
Overlap
 FBS overlapped by PCB weakness.
 FBS overlapped by GBS.

10. – Triad of Ophthalmoplegia, Ataxia & Areflexia.
– Diplopia f/b Gait & Limb ataxia. Other Cranial nerves;
Motor Power - Preserved
– Ocular signs:- Complete Ophthalmoplegia; Dilated &
Non-reactive Pupils; External ophthalmoparesis ± ptosis.
– C. jejuni (20%) and Haemophilus influenzae (8%)
– Anti-GQ1b (98%) (Anti-GT1a, Anti-GD3 and Anti-GD1b).
– 50 % of MFS develop PCB, BBE, and classic GBS in the
first 7 days after onset.
Miller Fisher syndrome (MFS)

11. Miller Fisher syndrome (MFS)
– EDX studies:- Axonal process (Sensory) with no or only mild Motor
Conduction abnormalities. SNAP- Normal (50%).Reduced or Absent
– Sural sparing pattern (one-third) .
– Brain MRI is usually Normal; Rare- Brainstem lesions or Contrast
enhancement of 3rd nerves.
– Favorable prognosis, Mean recovery time:- >10 weeks

12. Bickerstaff Brainstem Encephalitis (BBE)
– Progressive, relatively Symmetric External Ophthalmoplegia and Ataxia
by 4 weeks’ and ‘Disturbance Of Consciousness or Hyperreflexia’
– `BBE without Limb Weakness' and `BBE with Limb Weakness'.
– Others:- Ptosis; Facial Palsy; Dysarthria; Areflexia / Normal DTR;
Extensor plantars.
– CSF- Albuminocytological Dissociation; Absence does not preclude
diagnosis.
– Edx:- Normal (majority); Axonal; Demyelinating (Rare)
– MRI Brain:- T2 Hyperintensity Brainstem, Cerebellum, Thalamus,
or Subcortical White Matter.

13. Pharyngeal-Cervical-Brachial Variant
(PCB)
– <5% of GBS
– Facial palsy, Dysarthria, Weakness & Areflexia in UL.
– Anti-GQ1b & Anti-GT1a Ab

14. Acute Pandysautonomia
– Rapid onset of combined Sympathetic & Parasympathetic failure
– No Sensory and Motor involvement.
– DTR are usually lost during the course of the illness.
– Severe Orthostatic Hypotension, Heat Intolerance, Anhidrosis, Dry
Eyes & Mouth, Fixed Pupils, Fixed Heart Rate & Disturbances Of
Bowel & Bladder Function.
– Autoantibodies to Ganglionic Acetylcholine Receptors (50%)

15. Regional
GBS
 Pharyngeal-cervical-brachial Variant:-
 Polyneuritis Cranialis:-
 Rapid onset of symmetrical multiple Cr Nerve
palsies.
 Isolated Facial Diplegia With Distal Paresthesias
 Forme fruste of PCB variant.
 Sensory Ataxic Variant:-
 Acute Ataxia, Sensory loss, Areflexia;
 NCV s/o Demyelination; SNAPs - Normal (60%);
Reduced or absent (40%)
 GQ1b antibodies
 Acute And Painful Small-fiber Neuropathy:-
 Following CMV
 Good response to Steroids

16.  Sural Sparing Pattern:-
• Reduced amplitude or absent SNAPs in UL +Normal Sural
SNAPs - Specific; 50% positive during first 2 weeks.
 Sural sparing combined with abnormal F waves:-
• 96% specific
• Present in about 50% of AIDP.
• Two-thirds of patients <60 years during the first 2 weeks of
illness
 Sensory ratio:-
• Sural + Radial SNAPs/Median + Ulnar SNAPs
• Substitute for sural sparing pattern, (Elderly)
• High ratio (>1) is fairly specific
• Distinguishes GBS from other Axonal polyneuropathies.
NCV
Patterns
Normal NCS:- 50% in first 4 days; 10% in first week.

18.  15% - Mild condition, remain Ambulatory, and recover
after a few weeks.
 5%–20% - Fulminant course ; Ventilator dependence &
Axonal Degeneration (Within 2 days from Onset)
 Up to 30% - Require Ventilatory support.
 Between 2% and 5% - Die of complications.
 20% - Residual Motor Weakness – At 1 year later.
 Complete Recovery - 70% in 12 months &
82% in 24 months.
 Recurrence - Up to 5%.
 About 5% of patients – Acute onset CIDP.

19. 1. Older age (>60 years),
2. H/o Preceding Diarrheal Illness,
3. Recent CMV infection,
4. Ventilatory support,
5. Rapid progression (Max Deficit in <7 days,
6. Hyponatremia,
7. Low Distal CMAP amplitudes.
Predictors
for Poor
Recovery:-

20. Typical
CIDP

21. Pattern of Evolution:-
Continuous /
Stepwise
Middle & Elderly
Relapsing
Young
Pregnant ( 3rd Trimester
/ Post partum )
Acute onset
CIDP
GBS alongwith ≥1 of
following
1. Deteriorate after 8 wks
2. TRF > 2
3. Multiple focal
enlargement of nerve
(USG)
4. Sensory Prominent
5. Demyelinating features
on f/u (months later)

22. Clinical Features:-
– All Ages; 5th & 6th decade
– Symm Motor & Sensory; P=D; LL > UL ( majority)
– Sensory = Stocking Glove distribution
– Children = Precipitous onset; Gait disturbances.
– Others:-
– Postural tremors
– Enlarged peri nerve
– Facial / Bulbar weakness.
– Rare:- RF; ANS involm.

27. Clinical Criteria CIDP
Typical CIDP
All the following:
1. Prog. or Relapsing, symm., P & D weakness of UL & LL &
Sensory involvement of at least 2 limbs.
2. Developing over at least 8 weeks.
3. Absent or Reduced DTR in ALL limbs.

28. CIDP
Variants

29. CIDP Variants
• Distal CIDP: Distal sensory loss & weakness (LL)
• Multifocal CIDP: Sensory loss & weakness in a multifocal pattern
(asymmetric, UL, in >1 Limb)
• Focal CIDP: Sensory loss & weakness in Only one Limb.
• Motor CIDP: Motor s/s
• Sensory CIDP: sensory s/s

30. Acute onset CIDP
also k/a…. A-CIDP
– 13% of CIDP
– Deteriorate >8 weeks after onset or Relapse at least 3 times
after initial improvement.
– Often, remain ambulatory.
– Facial weakness, Respiratory or ANS involvement – Less likely
– Sensory signs – More likely
– No specific clinical features or laboratory tests that can
distinguish GBS from A-CIDP in the acute stage of the disease.
– IgG antibodies to Contactin 1

31. Multifocal Form Of CIDP
– Also K/a Lewis-Sumner variant; MADSAM (Multifocal Asymmetric
Demyelinating Sensory And Motor) Neuropathy.
– Multifocal distribution of weakness and sensory deficits.
– Usually affects UL first. LL later on. (sometimes at the onset)
– Cranial nerves (III, V, VII, X, XII) more frequently involved than in other
CIDP forms
– NCV -- Focal CB
– Good response to Steroids

32. DADS (Distal Acquired Demyelinating
Symmetric Neuropathy)
– Sensory loss in the Distal UL & LL , Gait Instability.
– Edx :- Symmetrical and Uniform slowing of Distal Latencies
more than CV; Rare CB.
– IgM monoclonal against MAG (50-70%)
– Usually respond poorly to therapy.
– Some patients respond favorably to IVIG or Rituximab.

33.  Focal CIDP:-
Rare
Usually affects the Brachialor Lumbosacralplexus,
But can affect individual peripheralnervesas well.
 Motor CIDP :-
RelativelySymmetric P & D Weakness.
Normal sensationClinically and EDx.
If sensory nerve conduction is abnormal in Clinically Motor CIDP; then the diagnosisis Motor-
PredominantCIDP.
Patients with Motor CIDP may deteriorate after corticosteroids.
 Sensory CIDP :-
Distrurbed cutaneous sensation
Gait Ataxia,
Impaired Vibration & Position sense
If Motor nerve conduction Slowing or CB are present -- then diagnosis is
Sensory-PredominantCIDP.
 Sensory CIDP is often a transient clinical stage that precedes the appearance of weakness in
about 70% of patients

34. Chronic Immune Sensory
Polyradiculopathy (CISP)
– Sensory Ataxia
– NCV -- Normal Motor & Sensory conduction studies.
– Abnormal somatosensory evoked responses,
– MRI LS spine - Enlarged lumbar roots
– Nerve root biopsy - Segmental Demyelination, Onion Bulbs & Endoneurial
Inflammation
– Respond to IVIG.

35. Chronic Immune Sensorimotor
Polyradiculopathy (CISMP)
– Both weakness & sensory symptoms
– Progressive / Stepwise / Recurrent symptoms.
– EDX studies -- Normal SNAPs & Normal CMAP
 (Some: Reduction of CMAP amplitudes)
 Abnormal F-waves and H-reflexes.
 Slowing or CB.
– MRI LS spine -- Enhancing caudal and lumbosacral roots.

36. 1) Sensory CIDP
• Sensory :- Prolonged Distal Latency, or Reduced SNAP
Amplitude, or Slowed CV in at least TWO nerves.
(2) Possible CIDP
• As in (1) but in only 1 nerve.
• Sensory CIDP with normal motor nerve conduction studies
• Needs to fulfil a. or b:
a.) Sensory Study: CV <80% of LLN (for SNAP Amplitude >80%
of LLN) or <70% of LLN (for SNAP Amplitude <80%
of LLN) in at least TWO nerves
b.) Sural Sparing Pattern
Sensory Nerve Conduction Criteria

37. Autoimmune
Nododopathies

39.  Node:-
 GM1
 GD1a
 Paranode:-
 Neurofascin isoform 155(NF-155)
 Contactin (CNTN)-1
 Contactin-associated protein (Caspr)
 GQ1b
 Sulfatide
 Juxtaparanodal (JPN):-
 Caspr2.
 CNTN-2 complexes.

40. Autoimmune Nodopathies
– Contactin-1 (CNTN1)
– Neurofascin-155 (NF155)
– Neurofascin Isoforms (NF140/186)
– Contactin-Associated Protein 1 (Caspr1)

41. Autoimmune Nodopathies
– IgG4 subclass
– Don’t Activate Complement or Cell-Mediated
Cytotoxicity
– (Exception: IgG3 CNTN1)
– Bind with high affinity to Antigens that, results
in disruption of the Axoglial interactions.

42. Anticontactin 1 Ab (CNTN1)
– Rapid-progressive CIDP;
– Ataxia;
– Early Axonal involvement
– a/w Nephrotic syndrome.
– Poor response to IVIG.
– Good response to Rituximab.
Miura Y, Devaux JJ, Fukami Y, Manso C, Belghazi M, Wong AH, et al. Contactin 1 IgG4 associates to chronic inflammatory
demyelinating polyneuropathy with sensory ataxia. Brain 2015; 138: 1484–91.

43. Anti-Neurofascin 155 Ab
(NF 155)
– c/f:- Subacute onset; Younger Age;
– Distal Motor Symptoms, Ataxia, Tremor with Cerebellar
features.
– Tremor of Head, Voice & Tongue tremor. Cr nerve involvement
– HLA DRB1*15
– Poor response to IVIG
– Ultrasound:- Nerve Enlargement (All).
– MRI Neurography:- Symmetric Hypertrophy of Cx & LS roots.
Devaux JJ, Miura Y, Fukami Y, Inoue T, Manso C, Belghazi M, et al. Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy. Neurology 2016; 86: 800–7.

44. AntiNeurofascin 140 ( NF140) &
AntiNeurofascin 186 (NF186)
– Acute Aggressive onset,
– Edx:-Conduction Blocks
– may a/w Nephrotic Syndrome
Stengel H, Vural A, Brunder AM, Heinius A, Appeltshauser L, Fiebig B, et al. Anti-pan-neurofascin IgG3 as a marker of fulminant
autoimmune neuropathy. Neurol Neuroimmunol Neuroinflamm 2019; 6: e603.

45. Contactin-Associated Protein 1
(Caspr1)
C/f:-
– Acute/ Subacute Neuropathy;
– Ataxia,
– Neuropathic Pain,
– Cranial nerve involvement
– Poor response to IVIg.
Doppler K, Appeltshauser L, Villmann C, Martin C, Peles E, Kramer HH, et al. Auto-antibodies to contactin-associated protein 1
(Caspr) in two patients with painful inflammatory neuropathy. Brain 2016; 139: 2617–30.

47. Nerve biopsies should be considered only when:
– Skilled Surgeons, Neuropathologists &
Specialized & Experienced Pathology laboratory
facilities are available.
– Symptoms are severe enough to justify the
potential morbidity associated with a nerve
biopsy.
– The low accuracy of the test is fully understood by
the patient before undergoing the biopsy.

48. Nerve Biopsy
CIDP is suspected
– But cannot be confirmed with the Clinical, Laboratory,
Imaging & Edx.
– There is little or no response to treatment, such that
an alternative diagnosis such as CMT, Amyloidosis,
Sarcoidosis, or Nerve sheath Tumours
/Neurofibromatosis might be considered.
European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory
demyelinating polyradiculoneuropathy: Report of a joint Task Force—Second revision 2021

49. – Sural Nerve / Superficial Peroneal Nerve.
– But Biopsy of a Clinically affected nerve (useful)
– Factors probably supporting the diagnosis of CIDP
may be:
o Thinly myelinated axons and small onion bulbs.
o Thinly myelinated or demyelinated internodes in teased
fibres
o Perivascular macrophage clusters.
– Features of Demyelination (EM).

50. Hypertrophic
Nerve Roots are
best appreciated
in parasagittal
image.

51. Typical CIDP :-
• AL amyloidosis, ATTRv polyneuropathy
• Chronic Ataxic Neuropathy Ophthalmoplegia M-
protein Agglutination Disialosyl Antibodies
(CANOMAD)
• Guillain-barré Syndrome
• Hepatic Neuropathy
• HIV-related Neuropathy
• Multiple Myeloma
• Osteosclerotic Myeloma
• POEMS Syndrome
• Uremic Neuropathy
• Vitamin B12 Deficiency

52. Distal CIDP :-
• Anti-MAG IgM neuropathy
• Diabetic neuropathy
• Hereditary neuropathies (CMT1, CMTX1, CMT4,
Metachromatic Leukodystrophy, Refsum
disease, Adrenomyeloneuropathy, ATTRv
polyneuropathy)
• POEMS syndrome
• Vasculitic neuropathy

53. Multifocal and Focal CIDP :-
• Diabetic radiculopathy/plexopathy
• Entrapment neuropathies
• Hereditary neuropathy with liability to pressure
palsies (HNPP)
• Multifocal motor neuropathy (MMN)
• Neuralgic amyotrophy
• Peripheral nerve tumours (such as Lymphoma,
Perineurioma, Schwannoma, Neurofibroma)
• Vasculitic neuropathy (Mononeuritis Multiplex)

54. Motor CIDP:-
• Hereditary Motor Neuropathies (such as
Distal Hereditary Motor Neuropathies,
Spinal Muscular Atrophy, Porphyria)
• Inflammatory Myopathies
• MND
• NMJ d/o (MG, LEMS)

55. Sensory CIDP:-
• Cerebellar Ataxia, Neuropathy, Vestibular Areflexia
Syndrome (CANVAS)
• CISP
• Dorsal column lesions (such as Syphilis,
Paraneoplastic, Copper deficiency, vit B12 deficiency)
• Hereditary Sensory Neuropathies
• Idiopathic Sensory Neuropathy
• Sensory Neuronopathy
• Toxic neuropathies (such as ACA and vit B6 toxicity)

56. Antibodies Disease
GM1 (IgM)
MMNCB (70%)
AMAN (30%)
AMSAN .
GQ1a Non Specific (No diagnostic value)
GQ1b (IgG)
MFS
BBE
GD1a (IgG)
AMAN (30%)
AMSAN .
GD1b (IgM)
CANOMAD
Pure Sensory Ataxic variant
GT1a Pharyngeal-cervical-brachial variant
GT1b Acute Ataxic variant
MAG (IgM) DADS (50-70%)
Antibodies
in AIDP &
CIDP

58.  Azathioprine
 Methotrexate,
 Mycophenolate Mofetil
May be Used As Corticosteroid-
sparing Adjunctive Agents In
Long-term Management
Bedi G, Brown A, Tong T, et alChronic inflammatory demyelinating polyneuropathy responsive to mycophenolate mofetil therapyJournal of
Neurology, Neurosurgery & Psychiatry 2010;81:634-636.

60. Six years after onset of illness,
56% - Good outcome,
24% - Deteriorated & Failed
to respond to all treatments,
11% - Died of complications
of the disease.

62. Inflammatory Neuropathy Consortium Base (INCbase)

63. IgG4 MAB
targeting
the classical
complement
system c1s.

64. ARGX-117 is antibody that binds specifically to C2 inhibiting the function of C2
and downstream complement activation

65. T
H
A
N
K
Y
O
U

66. Antibodies
in AIDP &
CIDP

67. Secondary CIDP
– Diabetes Mellitus,
– IgG or IgA Monoclonal Gammopathy of Undetermined Significance [MGUS],
– IgM Monoclonal Gammopathy without Antibodies to MAG
– HIV infection
– Malignancies.
– Drugs

68. Preceding Infections
– C. jejuni, Clostridium, Haemophilus influenza, Shigella
& Mycoplasma pneumonia.
– Viruses :- Zika virus, CMV, Hepatitis viruses (types A, B, C, and E),
HIV, EBV, SARS-CoV-19
- GBS following CMV ---- Sensory involvement.

70. Respiratory
failure
4 %
24 %
65 %
EGRIS (Erasmus GBS Respiratory Insufficiency Score)

71. Scores for Monitoring
– Bedside tool to monitor grip strength is the Martin Vigorimeter
– Rasch-built Overall Disability Scale (R-ODS):- validated for CIDP, GBS and
polyneuropathy associated with MGUS.
– INCAT-Overall Disability Sum Score (ODSS) :- poorly detects discrete
changes of disability or sensory symptoms
– INCAT sensory sumscore (ISS) :- records sensory symptoms GBS & CIDP

77. ANX 005 is an inhibitor of C1q protein complex designed to block the activation of the classical pathway