© 2003 By Default! A Free sample background from www.powerpointbackgrounds.com Slide 1 Antiganglioside antibody Anti-ganglioside antibodies The cause of.

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Presentation transcript:

© 2003 By Default! A Free sample background from Slide 1 Antiganglioside antibody Anti-ganglioside antibodies The cause of otherwise unexplained ophthalmoplegias? Michelle Gajus and Lionel Kowal

© 2003 By Default! A Free sample background from Slide 2 Antiganglioside antibody Antiganglioside antibodies are responsible for some autoimmune diseases Antiganglioside antibodies are responsible for some autoimmune diseases Antiganglioside antibody

© 2003 By Default! A Free sample background from Slide 3 Antiganglioside antibody Acute conditions Acute conditions – Miller-Fisher Syndrome – Acute ophthalmoparesis (ophthalmoplegia without ataxia) (ophthalmoplegia without ataxia) Chronic conditions Chronic conditions –Otherwise unexplained ophthalmoplegia Chronic ophthalmoplegia with anti-GQ1b antibody. Reddel et alii Neurology. 54(4):1000-2, Feb 2000 & some Japanese papers ANTI Gq1b

© 2003 By Default! A Free sample background from Slide 4 Antiganglioside antibody ANTIGM-1 Guillain-Barre syndrome Guillain-Barre syndrome Multifocal motor neuropathy Multifocal motor neuropathy Distal lower motor neuron syndrome Distal lower motor neuron syndrome McCombe: Asymmetric patchy muscle weakness McCombe: Asymmetric patchy muscle weakness

© 2003 By Default! A Free sample background from Slide 5 Antiganglioside antibody Five cases of anti GM-1 [normal anti-GQ1b] in ophthalmoplegia of obscure cause

© 2003 By Default! A Free sample background from Slide 6 Antiganglioside antibody EG - 13 y female ‘Acute’ ET ‘Acute’ ET Intermittent at first Intermittent at first No strabismogenic factors present No strabismogenic factors present 50^  70^ ET in one month 50^  70^ ET in one month BMR + botox : good result BMR + botox : good result

© 2003 By Default! A Free sample background from Slide 7 Antiganglioside antibody SN - 31 y female Ptosis surgery as a child Ptosis surgery as a child 3 years of intermittent LXT 3 years of intermittent LXT Other examination normal Other examination normal

© 2003 By Default! A Free sample background from Slide 8 Antiganglioside antibody

© 2003 By Default! A Free sample background from Slide 9 Antiganglioside antibody

© 2003 By Default! A Free sample background from Slide 10 Antiganglioside antibody

© 2003 By Default! A Free sample background from Slide 11 Antiganglioside antibody

© 2003 By Default! A Free sample background from Slide 12 Antiganglioside antibody

© 2003 By Default! A Free sample background from Slide 13 Antiganglioside antibody SN - 31 y female LMR Rs 10 mm to slightly restrict abduction, LMR Rs 10 mm to slightly restrict abduction, LLR Rc to LIO insertion LLR Rc to LIO insertion Cosmesis OK; no diplopia Cosmesis OK; no diplopia

© 2003 By Default! A Free sample background from Slide 14 Antiganglioside antibody JL - 50 y male Previously well; No HT, DM Previously well; No HT, DM Sudden onset R vertical diplopia Sudden onset R vertical diplopia Impaired depression RE; excyclo RE Impaired depression RE; excyclo RE ‘ R SOP of indeterminate cause ‘ ‘ R SOP of indeterminate cause ‘ No treatment No treatment Symptoms completely resolved over 5 mo Symptoms completely resolved over 5 mo

© 2003 By Default! A Free sample background from Slide 15 Antiganglioside antibody LK - 58 male LK - 58 male No HT, DM No HT, DM ‘Shimmering’ visual disturbance followed by diplopia ‘Shimmering’ visual disturbance followed by diplopia H&V diplopia esp. down left gaze H&V diplopia esp. down left gaze Exotropia on L gaze Exotropia on L gaze Provisional diagnosis R CN IV Provisional diagnosis R CN IV All resolved in 2 months All resolved in 2 months

© 2003 By Default! A Free sample background from Slide 16 Antiganglioside antibody JP - 67 female Past history of well-controlled hypertension Past history of well-controlled hypertension 4 months of intermittent diplopia on L gaze 4 months of intermittent diplopia on L gaze With glasses 6^ ET, with CL 1^ With glasses 6^ ET, with CL 1^ Orthophoric in primary position Orthophoric in primary position 1^ fusional divergence, 26^ of fusional convergence 1^ fusional divergence, 26^ of fusional convergence Normal ocular rotation,V1, pupillary reaction, MRI Normal ocular rotation,V1, pupillary reaction, MRI No abduction deficit No abduction deficit Diagnosis: subtle L VI with no localising signs Diagnosis: subtle L VI with no localising signs No treatment No treatment

© 2003 By Default! A Free sample background from Slide 17 Antiganglioside antibody Age/Gender13F31F50M58M67F Anti-GM1 IgG 4(N<10)N(N<20)1380(N<800)10(N<20)7(N<20) Anti-GM1 IgM 20(N<10) 38, 49 (N<20)3118(N<800)37(N<20)28(N<20) Anti- GQ1b NNNNN CT/MRINNNNN Investigation Results

© 2003 By Default! A Free sample background from Slide 18 Antiganglioside antibody Investigation Results Age/Gender13F31F50M58M67FTensilon Not done neg Diabeticscreen negnegnegneg ESR/CRPN NNN TFT N N

© 2003 By Default! A Free sample background from Slide 19 Antiganglioside antibody Nomenclature ‘Ganglioside’: lipids from ganglion cells of brain (Klenk ‘42) ‘Ganglioside’: lipids from ganglion cells of brain (Klenk ‘42) Oligoglycosylceramides with sialic acid residues joined to the monosaccharide units. Oligoglycosylceramides with sialic acid residues joined to the monosaccharide units. Short-hand nomenclature system: Short-hand nomenclature system: M, D, T, Q = mono-, di-,tri- & quatro- sialog-sides hence GQ, GM 1, 2, 3, etc refer to the order of migration of the g-sides on thin-layer chromatography. Order of migration of monos/g-sides is GM3 > GM2 > GM1 1, 2, 3, etc refer to the order of migration of the g-sides on thin-layer chromatography. Order of migration of monos/g-sides is GM3 > GM2 > GM1 To indicate variations within the basic structures, further subscripts are added, e.g. GM1a, GD1b. To indicate variations within the basic structures, further subscripts are added, e.g. GM1a, GD1b.

© 2003 By Default! A Free sample background from Slide 20 Antiganglioside antibody Distribution of anti-GQ1b GQ1b g-sides are clustered in paranodal region of human ocular motor nerves GQ1b g-sides are clustered in paranodal region of human ocular motor nerves Paranodal region: Paranodal region: - important for nerve conduction - important for nerve conduction - not protected by blood brain barrier or by connective tissue sheaths of the peripheral nerves. - not protected by blood brain barrier or by connective tissue sheaths of the peripheral nerves. GQ1b Ab’s can easily target these vulnerable sites. GQ1b Ab’s can easily target these vulnerable sites.

© 2003 By Default! A Free sample background from Slide 21 Antiganglioside antibody Distribution of GQ1b Other cranial and peripheral nerves

© 2003 By Default! A Free sample background from Slide 22 Antiganglioside antibody Anti-GM1 III, IV,VI : more GQ1b g-sides cf other cranial nn III, IV,VI : more GQ1b g-sides cf other cranial nn  propensity for ophthalmoplegia with GQ1b Ab’s.  propensity for ophthalmoplegia with GQ1b Ab’s. Concentration of GM1 g-sides in ocular motor nerves no higher than other cranial nn. Concentration of GM1 g-sides in ocular motor nerves no higher than other cranial nn.  mechanism of action of Ab’s against GM1 less clear than for GQ1b  mechanism of action of Ab’s against GM1 less clear than for GQ1b

© 2003 By Default! A Free sample background from Slide 23 Antiganglioside antibody Anti-GM1 In about 20 consecutive cases of acquired ophthalmoplegia of obscure cause: 5 positive cases for anti-GM1. In about 20 consecutive cases of acquired ophthalmoplegia of obscure cause: 5 positive cases for anti-GM1. Our finding suggests that they may play a part in some otherwise unexplained ophthalmoplegia. Our finding suggests that they may play a part in some otherwise unexplained ophthalmoplegia. Pathogenesis yet to be elucidated. Pathogenesis yet to be elucidated.