Immune Neuropathies Stanley Iyadurai, MSc PhD MD Assistant Professor of Neurology, Neuromuscular Specialist, OSU, Columbus, OH

August 28, 2015

Case

• 32-year old woman

• 1.5 year history of numbness/tingling/weakness

• Difficulty walking

3 months later

Inflammatory or Immune?

Not Clear

Inflammatory Cells – present or not?

Immune Components Deposited?

Immune-mediated Attack?

Involves Complement?

Involves Antibodies?

Inflammatory Markers are Absent?

Treat Inflammation/Use Immunomodulation?

Types

• Guillain-Barre Syndrome and variants

• CIDP and variants

• Multifocal Motor Neuropathy

• Paraneoplastic Neuropathies

Pathology

Ultrastructure

Muscle Biopsy

Guillain-Barre Syndrome

AIDP to Pure Motor, Sensory Motor, Bulbar and Miller-Fisher Syndrome

Hypothesis of Gangliosides mimicry of Campylobacter jejuni lipopolysaccharides

Ascending Weakness, Areflexia

Facial Weaknes

Increased CSF Protein

Acute Demyelinating Syndrome

Diagnosis

• Ascending Paralysis

• Areflexia

• Dysautonomia

• Nadir at 4-6 weeks

• Increased CSF Protein

• Demyelinating Velocities on EMG

• Conduction blocks

• Absent sensory responses

• Denervation – Fibs/Positive Sharp Waves

Motor-Sensory GBS

75% of GBS in Western Countries

Paresthesias

Facial Involvement

Autonomic Dysfunction

CMV infection in 20%

Pure Motor GBS

20% of GBS in Western Countries

(Paresthesias)

Distal Weakness in Extremities

Cranial Nerves, Respiratory Muscles Spared

C. jejuni 65%

IgG against GM1 abs - 40%

Miller-Fisher Variant

3% of GBS in Western Countries

Extraocular Muscle weakness, Ptosis

Paralysis of Sphincter Pupillae

Facial Weakness, Bulbar Involvement

Ataxia (50%)

IgG against GQ1b in 90%

GBS Treatment

IVIg, PE

For IgG against GM1 patients, IVIG > PE

Steroids not helpful – Harmful effects on denervated muscle or inhibit macrophage repair processes?

CIDP

• Previously known as “steroid-responsive neuropathy”.

• It affects 1 to 7.7 per 100,000 population

• Age of onset: 2 to 72 years of age with more prevalence in the fifth decade

CIDP

• chronic, monophasic/progressive or relapsing-remitting disease

• Characterized by proximal and distal weakness, in addition to sensory symptoms for more than 2 months

• On exam, hyporeflexia/areflexia is diffuse and it is usually a common finding on exam

• Objective sensory loss of 1 or more sensory modalities is present in 86% of cases

CIDP

Autoimmune!

Progressive or Relapsing/remitting

Proximal and Distal, Symmetric Weakness

Sensory Involvement + Areflexia; Variants

8 Weeks to Reach Nadir

EMG – Prolonged DL, Slowed NCV, Delayed or Absent F-waves, Conduction Block, Temporal Dispersion

CSF with Increased Protein

CIDP

CIDP Diagnosis

• Clinical Picture

• Cerebrospinal fluid

• Electrodiagnostic studies

• Nerve or Nerve and Muscle biopsy

CIDP Variants

• Typical CIDP constitutes about 50 % of cases of CIDP

• The rest constitutes “CIDP variants”

Major CIDP variants:

• Distal Acquired Demyelinating symmetric polyneuropathy (DADS)

• Lewis-Summer syndrome or Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM)

• Sensory predominant CIDP

• Motor predominant CIDP

• Focal CIDP

CIDP - Treatment

Prednisone, IVIg, PE

Long-term Treatment

Multifocal Motor Neuropathy

IgM against GM-1 antibodies (85%)

Pure Motor disease

Focal weakness

Involvement of subsegments of terminal nerves

Treatment with IVIg, rituximab

Multifocal Motor Neuropathy

Multifocal Motor Neuropathy

Distal Acquired Demyelinating symmetric polyneuropathy (DADS) • Accounts 2 to 17% of CIDP cases

• Distal form of CIDP

• It is characterized mainly by sensory symptoms, although abnormal motor nerve conduction studies in form of demyelinating disease can be observed.

• CSF shows elevated protein in 86% of cases

• In 2/3 of cases, an abnormal monoclonal protein (M protein) on serum protein electrophoresis or IFE is found, and in 2/3 of those, antibody against Myelin-Associated Glycoprotein (MAG)

• Poor response to Immunotherapy, and treatment is mostly supportive

MAG Neuropathy

Lewis-Summer syndrome or Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM) • It accounts 6-15% of CIDP cases

• It is a distal form of CIDP

• Males are commonly affected in the fifth decade

• Upper extremities are affected mostly (Lower extremities are involved in 38% of cases

• Mistaken as entrapment neuropathies at median and ulnar nerves (wrist and elbow respectively).

• Cranial nerve involvement including II, III, IV and V has been reported

MADSAM

• Main electrodiagnostic feature is conduction block (importance to have proximal stimulation at Erb’s point)

• CSF protein is normal or mildly elevated

• Intravenous Immunoglobulin is the first line treatment

Sensory Predominant CIDP

• It accounts for 6-12% of CIDP

• Symptoms are sensory and include the following: numbness and tingling in “stocking-glove distribution”, neuropathic pain, or proprioception deficit leading to sensory ataxia.

• Strength is usually normal

• On electrodiagnostic studies, demyelinating changes are seen in motor as well in sensory nerves

• Treatment if clinically disabled

Motor CIDP

• Pure Motor form of CIDP

Focal CIDP

• Only in specific location

Other Dysimmune Neuropathies

• Anti-Hu syndrome • Treat cancer

• Anti-SS-A, SS-B • Hydroxychloroquine

• MGUS (monoclonal gammopathy of unknown significance) • Plasma Exchange, cyclophosphamide

• POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, Skin changes) • Plasma Exchange, cyclophosphamide, Stem cell transplant?

• GALOP (Gait disorder, autoantibody, Late-onset, Polyneuropathy) • ??

Hereditary neuropathies

Chronic sensory neuropathy

High arches & Hammer toes

Preserved gastrocnemius size

CMT 1A

PMP-22 duplication CMT 1X

CMT 2A2