Stanley Iyadurai, MSc PhD MD Assistant Professor of ...
Transcript of Stanley Iyadurai, MSc PhD MD Assistant Professor of ...
Immune Neuropathies Stanley Iyadurai, MSc PhD MD Assistant Professor of Neurology, Neuromuscular Specialist, OSU, Columbus, OH
August 28, 2015
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
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 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
Multifocal Motor Neuropathy
IgM against GM-1 antibodies (85%)
Pure Motor disease
Focal weakness
Involvement of subsegments of terminal nerves
Treatment with IVIg, rituximab
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
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
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) • ??