Multiple sclerosis allied demyelinating diseases neuroimmunology glycobiology
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Multiple Sclerosis Allied Demyelinating Diseases Neuroimmunology & Glycobiology. 蔡清標 副教授 Msci MD 國立陽明大學 台北榮民總醫院. Figure 2. BI 2004 Essential Animal Cell Biology. Cell membranes 1 The lipid bilayer. Dr Gordon McEwan Department of Biomedical Sciences. Lipid bilayer. Lipid bilayer

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Multiple sclerosis allied demyelinating diseases neuroimmunology glycobiology

Multiple Sclerosis Allied Demyelinating DiseasesNeuroimmunology & Glycobiology

蔡清標 副教授 Msci MD

國立陽明大學

台北榮民總醫院



Multiple sclerosis allied demyelinating diseases neuroimmunology glycobiology

BI 2004

Essential Animal Cell Biology

Cell membranes 1

The lipid bilayer

Dr Gordon McEwan

Department of Biomedical Sciences


Multiple sclerosis allied demyelinating diseases neuroimmunology glycobiology

Lipid bilayer

Lipid

bilayer

(5 nm)

Protein

molecule

Lipid

molecule

Adapted from ECB Fig 11-4


Myelin antigen proteins and lipids
Myelin antigen : proteins and lipids

  • PROTEINS

  • proteolipid protein

  • myelin basic protein

  • wolfgram fraction

  • myelin associated glycoprotein MAG


Myelin antigen proteins and lipids1
Myelin antigen : proteins and lipids

  • LIPIDS

  • Glycolipid

  • galactocerebroside

  • sulfatide

  • gangliosides. GM1 GM4 etc


Glycosphingolipids in peripheral neuroapthies
glycosphingolipids in peripheral neuroapthies

  • glycosphingolipids --cell surface molecules

    • hydrophilic sugar moiety

    • hydrophobic ceramide

    • as autoantigens development of certain autoimmune diseases

    • antigen reaction side at sugar moiety


Glycolipid terminology and structure
Glycolipid terminology and structure

  • long chain aliphatic amine sphingosine (acylated ceramide)

  • attached to one or more sugars

  • ceramide immersed in the lipid bilayer

  • carbonhydrate structure exposed extracellularly


Glycolipid structures
Glycolipid structures

  • cerebroside -- monohexosyl ceramide

  • galactocerebroside -- galactosyl ceramide

  • sulfatide -- galactocerebroside sulfated in the carbon-3 position main antigen in sensory predominantly neuropathies


Glycolipid structures1
Glycolipid structures

  • gangliosides

  • complex glycosphingolipids

  • sialic acid residues M mono D di T tri GM1 G ganglioside M mono sialic acid 1 sequence of migration by TLC


Gangliosides in the brain
Gangliosides in the brain

  • four major gangliosides in the brain

  • GM1

  • GD1a

  • GD1b

  • GT1b



Vascular endothelium
Vascular Endothelium

SevereendothelialGL-3 accumulation


Multisystemic manifestations

Neurologic

Dermatologic

Ocular

Gastrointestinal

Renal

Cardiac

Cerebrovascular

Multisystemic Manifestations

Progressive accumulation of GL-3 causes increasing involvement of multiple organ systems.


Signs and symptoms
Signs and Symptoms

Early ischemic stroke

Left ventricular hypertrophy

Hypohidrosis

Progressive renal insufficiency

Angiokeratomas

Acroparesthesia

Acroparesthesia


Demyelination and dysmyelination
Demyelination and Dysmyelination

  • Adrenoleukodystrophy

  • X-linked recessive 1/20,000

  • Impairment in peroxismal oxidation of very long chain fatty acids

  • Accumulation in the brain and adrenal gland


Adrenoleukodystrophy
Adrenoleukodystrophy

  • 4 y/o bronzing skin

  • 7 y/o dysarthria, dysphonia, quadriparesis

  • 8 Y/o seizure

  • Decerebrate posture bed ridden before death


Glycolipids
glycolipids

  • autoantigens for the development of autoimmune diseases

  • demyelinating polyneuropathy

  • motor neuron disease

  • multiple motor neuropathy with conduction block

  • AIDP CIDP


Reaction site of glycolipid antibody
Reaction site of glycolipid antibody

  • react with epitopes on the carbonhydrate region

  • shared reactivity for bacterial lipopolysaccharides

  • react with SGPG and MAG


Anti glycolipid antibodies are pathogenic
Anti-glycolipid antibodies are pathogenic

  • improved disease progression and clinical S/S accompanying a decreased antibody titer

  • therapeutic reduction of these antibodies by plasmapheresis immunosuppressents


Ganglioside antibodies in patients with neuropathy
Ganglioside antibodies in patients with neuropathy

  • Acute inflammatory demyelinating polyneuroapthy AIDP 30% with GM1 Ab

  • Chronic inflammatory demyelinating polyneuropayhy CIDP

  • multiple motor neuropathy with conduction block MMN

  • Lower motor neuron syndrome LMNS

  • GQ1b in Miller Fisher Syndrome 90% GBS 2.7%



Glycosphingolipids in peripheral neuroapthies1
glycosphingolipids in peripheral neuroapthies

  • MAG Myelin associated glycoprotein and SGGL

    • MGUS monoclonal gammopathy

  • Sulfatide antibody

    • Sensory neuronopathy

  • GQ1b ganlioside

    • Miller-fisher syndrome


Antibodies to sulfatides
Antibodies to sulfatides

  • Pestronk et al 1991 sulfatide antibodies

  • Sensory neuropathy esp in sensory axonopathy

  • primary Sjogren syndrome

    • first case report in Taiwan

  • bind to DRG neuron sensory axon

  • acidic glycolipid SGGL MAG


Glycosphingolipids in peripheral neuroapthies2
glycosphingolipids in peripheral neuroapthies

  • glycosphingolipids are constituents of nerve cells

  • antibodies to glycosphingolipids found in certain autoimmune disorders

  • GM1 in

    • GBS Guillain-Barre syndrome

    • MMN multiple motor neuropathy

    • MND motor neuron disease

    • LMN lower motor neuron syndrome


Serum anti gm1 antibodies in patients with motor neuron disease
Serum anti-GM1 antibodies in patients with motor neuron disease

  • A Pestronk USA 1988 Neurol

  • High GM1 Ab in ALS

  • ALS 42/74 57% normal control 2/23 9%

  • Lower ALS 21/29 72% Upper ALS 1/15 7% Upper and Lower ALS 20/30 67%


Serum anti gm1 antibodies in patients with motor neuron disease1
Serum anti-GM1 antibodies in patients with motor neuron disease

  • Salazar-Grueso USA 1990 Ann Neurol

  • MND 9/48 19% OND -- Other neurological disease 4/40 10%

  • As frequent as other neurological disease

  • Markedly elevated titer -- more significant


Clinical correlations of anti gm1 antibodies in als and neuropathy
Clinical correlations of anti-GM1 antibodies in ALS and Neuropathy

  • Nancy L LAMB USA 1991 Muscle & Nerve positive titer

  • ALS 7/16 44% 57

  • ALS and gammopathy 6/6 100% 246

  • Motor CIDP 10/13 77% 562

  • Motor neuropathy 7/9 78% 556


Serum anti gm1 antibodies in patients with motor neuron disease2
Serum anti-GM1 antibodies in patients with motor neuron disease

  • C.Voumvourakis Athens Greece 1992 E.Neurol

  • 100 individuals 20 with MND 25 with PN and 40 controls

  • significant P<0.05 IgM GM1 Ab in MND


Serum anti gm1 antibodies in patients with motor neuron disease3
Serum anti-GM1 antibodies in patients with motor neuron disease

  • W-J HSU Hsu-Chuan China 1992

  • Lower ALS 4/6 67% Upper ALS 4/6 67% Upper and Lower 9/14 64.2 Control 2/18 11.1% P<0.001


Population based case control study
Population based case control study disease

  • Willison HJ UK 1993 J. Neurological Sciences

  • 82 cases of MND and matched for age sex and geographical area

  • GM1 antibodies in 26% MND and 18% Controls no significant autoimmune basis in sporadic ALS


Serum anti gm1 antibodies in patients with motor neuron disease4
Serum anti-GM1 antibodies in patients with motor neuron disease

  • C-P TSAI TAIWAN 1994 CMJ

  • MND 32/52 62% PN 10/38 26%

  • Upper and Lower ALS 7/22 32% Lower ALS 25/30 83% All ALS 32/52 62%


Diagnostic value of gm1 antibodies in motor neuron disorders
Diagnostic value of GM1 antibodies in motor neuron disorders

  • Van Schaik IN The Netherlands 1995 Neurology

  • The frequency of GM1 antibodies ranged from MMN 0-100% GBS 0-33% ALS 0-65% LMN 0-81% CIDP 0-77%


Diagnostic value of gm1 antibodies in motor neuron disorders1
Diagnostic value of GM1 antibodies in motor neuron disorders

  • RK YU Richmond USA

  • anti-GM1 antibody titer in most cases of ALS are considerably lower than those in LMN and motor neuropathy


Pathogenesis of gm1 antibodies
Pathogenesis of GM1 antibodies

  • antibodies to GM1 at the nodes of Ranvier in human and experimental autoimmune neuropathy Microscopy Research and Technique 1996

  • anti-GM1 M-protein damage human spinal cord neurons co-cultured with muscles Journal of the Neurological Sciences 1993


Pathogenesis of gm1 antibodies1
Pathogenesis of GM1 antibodies

  • antibodies to GM1 at the nodes of Ranvier in human and experimental autoimmune neuropathy Microscopy Research and Technique 1996

  • anti-GM1 M-protein damage human spinal cord neurons co-cultured with muscles Journal of the Neurological Sciences 1993


Conclusion
Conclusion

  • GM1 antibodies elevated in many cases with neurological disease

  • ALS -- elervated but low titer

  • Lower motor neuron syndrome -- high titer

  • MMN with conduction block -- high titer

  • Treatment not effective in cases without conduction block


Guillain barre syndrome clinical spectrum
Guillain-Barre syndrome clinical spectrum

  • AIDP

  • AMSAN C. Jejuni cross reaction GM1 axonal loss axolemma at nodes of Ranvier

  • Miller-Fisher some C. Jejuni strain GQ1b nodal region of 3 rd nerve and cerebellar neuron


Multiple sclerosis allied demyelinating diseases neuroimmunology glycobiology

Figure 1

Figure 1 GQ1b and LPS core OS structures. The entire structure for GQ1b is shown. Other gangliosides and core LPSs are highlighted. NeuAc = N-acetyl neuraminic acid; Gal = galactose; GaINAc = N-acetyl galactosamine; X = Glc (1->1) ceramide (gangliosides) or the remaining core OS/lipid A (LPSs).

From:   Goodyear: J Clin Invest, Volume 104(6).September 1999.697-708


Guillain barre syndrome
Guillain-Barre syndrome

  • Diagnosis criteria 1.Required progressive weakness and areflexia 2.supporting progressive days to weeks realtively symmetry mild sensor cranial nerve autonomic dysfunction and CSF protein


Guillain barre syndrome1
Guillain-Barre syndrome

  • Epidemiology 1.3-1.9/100,000 Taiwan 400/year

  • occur in all ages

  • peak in adult

  • another peak in the elderly 8.6/100,000 over 70Y/O


Guillain barre syndrome2
Guillain-Barre syndrome

  • preceding events

  • antecedent infection 2/3

    patients had URI or GI disturbance eg. diarrhea

  • onset to peak plateau 11days

  • virus: CMV 10-20% EB 10%

  • Campylobacter Jejuni 20-40%

    HS-19 AMSAN 60%

  • GM1 AMSAN GQ1b MFS


Guillain barre syndrome3
Guillain-Barre syndrome

  • vaccine and GBS

  • rabies antigen 1890

  • Swine-flue influenza 1976 slightly elevated risk of GBS

  • Recent studies at N Eng J Med no relationship


Guillain barre syndrome4
Guillain-Barre syndrome

  • AMSAN and AMAN

  • 10-20% of GBS

  • primary immune reaction attack directed on nerve axons EMG showed CMAPs

  • more severe form

  • ventilation in 2-4 days

  • poor recovery

  • biospy: axonal degeneration


Guillain barre syndrome5
Guillain-Barre syndrome

  • AMAN and AMSAN

  • Campylobacter Jejuni

  • in North China

  • 60-70% seropositive to

  • C.Jejunipathology showed IgG to the axolemma at node of Ranvier


Guillain barre syndrome6
Guillain-Barre syndrome

  • MFS Miller-Fisher Syndrome

  • another serotype of C.Jejuni

  • GQ1b antibody 96%

  • GQ1b in nodal region of oculomotor nerve, dorsal root ganglion and cerebellum

  • ophthalmoplegia, ataxia and areflexia


Gq1b in miller fisher syndrome
GQ1b in Miller-Fisher Syndrome

  • lipopolysaccharides in Campylobaccter jujuni

  • surface epitope

  • C jujuni GalNacB1-4GalB1-4GlcB1

    • Neu5Aca2

    • GQ1b 3GalNacB1-4GalB1-1

    • Neu5Aca2-8neu5Aca2


Gq1b in miller fisher syndrome1
GQ1b in Miller Fisher syndrome

  • Yuki et al 1993 GQ1b in MFS related to ataxia ophthalmoplegia

  • immnnostaining at paranodal region of human oculomotor trochlear and abducences with GQ1b monoclonal antibodies

  • GQ1b binding to cerebeller molecular layer 1996 Kornberg St louis

  • anti cerebellar antibody 1995 Japan


Post infectious neuritis
post-infectious neuritis

  • facial palsy

  • isolated 3rd 4th 6th nerve palsy

  • vestibular neuritis (Yu RK 1997 63.6% SGLPG rich in inner ear and cochlear nerve)

  • hypoglossal neuritis

  • cranial polyneuropathy (1997 Matsuchiba et al)


Why post infectious
Why post infectious?

  • Campylobacter jejuni lipopolysaccharides share the same epitope of ganglioside

  • 3 group 1. motor GBS and CJ infection GM1 2. sensory GBS and EBV 3. motor and cranial n. CJ and GQ1b


Why different virus induce same aidp
why different virus induce same AIDP ?

  • virus and interferon

  • alpha beta and gamma interferon

  • gamma interferon induced expression of class II

  • myelin cell act as Antigen presenting cell APCs

  • ongoing autoimmune demyelination occurred


Why different nerve
why different nerve?

  • Sulfatide, SGGL rich in dorsal root ganglion

  • GQ1b rich in oculomotor nerve 1993 Chiba et al

  • 11.6- 13.2 % in oculomotor and 5.2-8.4% in other nerve


Pathophysiology of gbs
Pathophysiology of GBS

  • humoral or cellular mechanism

  • activation of complement and deposition of membranolytic attack complex on myelin

  • circulating antiganglioside antibody

  • cytokines interferon

  • autoimmune disordertriggered by antecedent bacteria or viral infection


Multiple sclerosis allied demyelinating diseases neuroimmunology glycobiology

IFN- b


Multiple sclerosis allied demyelinating diseases neuroimmunology glycobiology

Figure 1

Figure 1 GQ1b and LPS core OS structures. The entire structure for GQ1b is shown. Other gangliosides and core LPSs are highlighted. NeuAc = N-acetyl neuraminic acid; Gal = galactose; GaINAc = N-acetyl galactosamine; X = Glc (1->1) ceramide (gangliosides) or the remaining core OS/lipid A (LPSs).

From:   Goodyear: J Clin Invest, Volume 104(6).September 1999.697-708


Gq1b in miller fisher syndrome2

GQ1b in Miller Fisher Syndrome

Ching-Piao TSAI Msci MD

Neurological Institute

Veterans General Hospital TAIPEI


Miller fisher syndrome
Miller-Fisher Syndrome

  • 49 GBS and 11 MFS in the past 10 years

  • age 12-78

  • mean age of onset 44

  • 8 males and 3 females

  • 4/5 had positive GQ1b antibodies


Guillain barre syndrome7
Guillain-Barre syndrome

  • Primary care

  • 33% cases need ventialtion

  • autonomic and hemodynamic changes

  • arrhythmia

  • airway protect

  • bowel care and nutrition

  • pain management

  • mortality 5-8%


Treatment of guillain barre syndrome
Treatment of Guillain-Barre syndrome

  • steroid : methylprednisolone

  • immunosuppressive : fucidin

  • interferon

  • CSF pheresis

  • plasmapheresis

  • IVIG

  • PP and IVIG

  • IVIG and methylprednisolone


Treatment of guillain barre syndrome1
Treatment of Guillain-Barre syndrome

  • plasmapheresis

  • North American trial of 245 cases

  • within 2 weeks of the disease

  • 122 PP 50ml/kg 5 changes

  • 123 convential treatment


Treatment of guillain barre syndrome2
Treatment of Guillain-Barre syndrome

  • Results wean ventilator ambulation

  • PP 24 days 53 days

  • control 53 days 85 days

  • 1 year later PP 71% control 52% full motor strength

  • less ICU days

  • no effect after 2 weeks


Treatment of guillain barre syndrome3
Treatment of Guillain-Barre syndrome

  • secondary worsening persistent active phase or antibody rebound impreoved by additional changes

  • recommendation

    2 changes for mild and 4-5 for severe

  • start as soon as possible


Treatment of guillain barre syndrome4
Treatment of Guillain-Barre syndrome

  • IVIG 1992

  • Netherland 150 GBS

  • 0.4gm/kg for 5 days vs PP

  • equal efficiency

  • not equally matched of the 2 group


Treatment of guillain barre syndrome5
Treatment of Guillain-Barre syndrome

  • 1997 Hughes 383 cases 38 centers in 11 countries 121 PP 50ml/kg 5 changes 130 IVIG 0.4gm/kg /day for 5 days

  • 128 PP and IVIG

  • PP and IVIG had similar effect

  • combination of PP and IVIG no additional effect


Guillain barre syndrome8
Guillain-Barre syndrome

  • IVIG plus methylprednisolone IVIG 0.4gm/kg and MP 500mg/day

  • 1994 Ann Neurol Dutch GBS group

  • 19/25 (76%) improved one score in IVIG plus MP infusion after 4 weeks

  • 39/74 (53%) IVIG alone

  • remove humoral factor and B cell function


Guillain barre syndrome9
Guillain-Barre syndrome

Appropriate number of PP?

  • mild walk more than 5m can not run

    2 courses of PP

  • moderate unable to stand unaided

    4 pp

  • severe ventilator needed

    6 PP


Guillain barre syndrome10
Guillain-Barre syndrome

  • Lancet 1997 London RAC Hughes

  • IVIG PP PP + IVIG

  • seven point disability grade score

  • 0. health 1. minor S/S able to run 2.able to walk 5m without aid 3. able to walk 5m with aid 4. unable to walk bed bound 5. require ventialtion 6. dead


Guillain barre syndrome11
Guillain-Barre syndrome

  • 4 weeks later

  • PE 0.9 point

  • IVIG 0.8

  • PE and IVIG 1.1

  • secondary outcome measure : time to recovery of unaided walking, DC ventilation, recovery from disability

  • PE and IVIG of equal effect combination of PP and IVIG do not confer better


Ivig and pp for gbs in vgh
IVIG and PP for GBS in VGH

  • IVIG 8 cases 3 with ventilator weaning 7-28 days

  • PP 10 cases 4 with ventilator weaning 9-32 days

  • PP and IVIG ventialtor 21 days ventialtor


Guillain barre syndrome12
Guillain-Barre syndrome

  • steroid : no effect

  • methylprednisolone ?

  • Lancet 1993 double-blind trial

  • IVMP 500mg/day for 5 days

  • 0.06 grade improve in the IVMP vs control

  • conclusion: IVMP is ineffective in GBS


Guillain barre syndrome13
Guillain-Barre syndrome

  • CSF filtration CSFF Germany Wollinsky KH

  • compared with PP

  • 32 GBS 15 with CSFF daily filtration 200-300 ml 17 with PP

  • PP 23D and CSFF 23.5 one score improvement

  • PP 51 CSFF 43 walking unaid

  • PP and CSFF equal effective


Treatment of gbs with interferon
Treatment of GBS with interferon

  • 47 Y/O male

  • diarrhea and flue like syndrome

  • 1 week later severe paresis of 4 limbs

  • C jejuni 1:128 GM1 1:400

  • abscence responses to PP

  • EMG/NCV peroneal and tibial <0.1MV

  • slow NCV 38-35m/sec normal sensory

  • molecular mimicy cross reaction with ganglioside surface

  • GBS--AIDP 85% Sc cell, demyelination

  • GBS--Axonal form 15% axonal GM1


Treatment of gbs with interferon1
Treatment of GBS with interferon

  • cytokine : inetrferon in EAN

  • MHC expression

  • MS Beta interferon decreases the severity of MS relapse

  • modulates the course of experimental allergic neuritis EAN


Treatment of gbs with interferon2
Treatment of GBS with interferon

  • 4 courses of plasma phresis 50ml/kg QOD

  • day 12 B-interferon 6 MIU/QOD

  • day 28 treatment interrupted

  • patient can walk 10m without aid

  • 1 year later able to walk for 1 km


Guillain barre syndrome14
Guillain-Barre syndrome

  • immunosuppressant

  • sodium fusiadte (fucidin)

  • 1.5gm/week

  • rapid decline in the cytokine concentration

  • interleukin-2 , gamma-interferon ,TNF


Guillain barre syndrome15
Guillain-Barre syndrome

Poor prognosis

  • 1. age greater than 60Y/O

  • 2. rapid progression to quadriplegia in 7 days

  • 3. need ventialtion

  • 4.CMAPs less than 20%

  • 5. preceding events with diarrhea


Ivig immunomodulatory actions
IVIG Immunomodulatory actions

  • inhibition of complement deposition

  • neutralization of cytokines

  • modulation of Fc-receptor mediated phagocytosis

  • down regulation of autoantibody regulation


Effect of ivig in neurological disease
Effect of IVIG in Neurological Disease

  • Guillain-Barre syndrome

  • multifocal motor neuropathy MMN

  • CIDP

  • dermatomyositis

  • myasthenia gravis

  • myasthenia syndrome


Effect of ivig in neurological disease1
Effect of IVIG in Neurological Disease

  • inclusion body myositis

  • paraneoplastic IgM demyelinating polyneuropathy

  • intractable childhood epilepsy

  • multiple sclerosis

  • optic neuritis


Safety of ivig
Safety of IVIG

  • 3000-10000 donors each batch

  • HIV

  • hepatitis A B C

  • inactivated by fractionantion process

  • low pH detergents and enzyme

  • CJD


Adverse reaction of ivig
Adverse reaction of IVIG

  • aseptic meningitis

  • skin reaction

  • thromboembolic events

  • renal tubular necrosis


Cost of treatment
Cost of treatment

  • 0.4gm/kg 25gm/day 12.5gm/10 bot/5days

  • USA 6440-11200 USD/month

  • Taiwan 600 USD/bot 6000 USD/per course

  • 180,000 - 200,000 NT/per course


Ivig in cidp
IVIG in CIDP

  • steroid first choice

  • 1994 Dyck PJ 20 cases controlled randomized cross over equally effective in muscle strength and CMAPs amplitudes

  • 1995 Hahn AF IVIG double-blind placebo-controlled cross over


Ivig in lower motor neuron syndrome
IVIG in lower motor neuron syndrome

  • lower motor neuron syndrome with elevated GM1 antibody

  • poor responses to cyclophosphamide

  • Kimura J reported 2 cases

  • no conventional conduction block block may be at the proximal part


Ivig in mmn with conduction block
IVIG in MMN with conduction block

  • poor responses to steroid and PP

  • 1993 Chaudhry V Ann Neurol

  • 1993 Nobile-Orazio Neurology good responses to IVIG

  • GM1 antibody not changed but IVIG can inhibit the binding of GM1 antibody to target antigen


Ivig in polyneuropathy with monoclonal gammapathy
IVIG in polyneuropathy with monoclonal gammapathy

  • 1995 Dalakas MC Ann neurol 3/11 cases improved after medication

  • MAG and anti-glycolipid antibody not changed after IVIG


Ivig in monoclonal gammapathy with polyneuropathy
IVIG in monoclonal gammapathy with polyneuropathy

  • over 50Y/O 1/100 and 70Y/O 3/100 had paraproteinemia

  • 63% MGUS

  • 12% MM

  • 9% Amyloid

  • 8% CLL lymphoma


Ivig in monoclonal gammapathy with polyneuropathy1
IVIG in monoclonal gammapathy with polyneuropathy

  • 10% of MGUS monoclonal gammapathy of unknown significance had polyneuroapthy

  • idiopathic polyneuropathy 6-10% had paraproteinemia

  • MGUS IgG A M

  • IgG A mainly motor

  • IgM mainly sensory


Ivig in monoclonal gammapathy with polyneuropathy2
IVIG in monoclonal gammapathy with polyneuropathy

  • IgM MGUS

    aged people

    sensory predominant

    progressive mild

    MAG (+) demyelination

  • CIDP

    all ages

    sensory motor

    recurrent


Ivig in myasthenia gravis
IVIG in myasthenia gravis

  • 1991 Cosi V Acta Neuro Scand

  • 1994 Gajdos P Clin exp Immunol 60% improvement

  • similar efficacy to PP

  • many variable in MG

  • well designed controlled study needed


Ivig in miscellaneous
IVIG in miscellaneous

  • Seizure

  • Rasmussen syndrome with antibody to glutamate receptor

  • intractable seizure such as Lennox-Gastaut syndrome

  • assumption that the seizure is caused by post-viral encephalitis

  • syndeham chorea

  • viral encephalitis


Ivig in miscellaneous1
IVIG in miscellaneous

  • Jaan S 1992 J NNP 70% polymyositis had mild to moderate improvement after IVIG

  • Multiple Sclerosis Lancet 1997 Australian MS group 148 cases relapsing-remitting MS monthly infusion of IVIG for 2 yrs

  • improve the course and reduce the relapsing frequency


Suggestion for ivig
Suggestion for IVIG

  • MMN and Myositis unresponsive to standard regimen

  • GBS CIDP

    as effective as PP considered Ist choice

  • MG myasthenia crisis in the elderly