388.1 ๐ŸŽ“ ้†ซๅญธ็”Ÿ็‰ˆ

388.1.0.1 ๐Ÿ“Œ ไธ€้ ้‡้ปž

388.1.0.1.1 NMOSD ็š„ๆœฌ่ณช

NMOSD ๆ˜ฏ่‡ช้ซ”ๅ…็–ซๅฐ CNS ไธญ aquaporin-4 (AQP4) ๆฐด้€š้“่›‹็™ฝ็š„ๆ”ปๆ“Šใ€‚AQP4 ๅœจๆ˜Ÿๅฝข่† ็ดฐ่ƒž (astrocyte) ็š„่ถณ็ช (footplates) ไธŠๅคง้‡่กจ็พ๏ผŒ็‰นๅˆฅๆ˜ฏ่ฆ–็ฅž็ถ“ใ€่„Š้ซ“ใ€่…ฆๅนน area postremaใ€้–“่…ฆใ€‚ๆŠ— AQP4 ๆŠ—้ซ” (AQP4-IgG, ๅˆ็จฑ NMO-IgG) ็ตๅˆๅˆฐ AQP4 โ†’ ๆดปๅŒ–่ฃœ้ซ” โ†’ ๆ˜Ÿๅฝข่† ็ดฐ่ƒžๆญปไบก โ†’ ไบŒๆฌก่„ซ้ซ“้ž˜ + ็ฅž็ถ“ๅ…ƒๆๅ‚ทใ€‚

้€™ๆ˜ฏไธ€ๅ€‹ IgG-mediated + complement-mediated ็–พ็—… (่ˆ‡ MS ไธป่ฆ็š„ T-cell mediated ไธๅŒ)ใ€‚

388.1.0.1.2 NMOSD ่ˆ‡ MS ็š„้—œ้ตๅทฎ็•ฐ

้ŽๅŽป NMOSD ่ขซ่ชค่ช็‚บ MS ็š„่ฎŠ็•ฐๅž‹๏ผŒไฝ†็พๅœจๆˆ‘ๅ€‘็Ÿฅ้“ๅฎƒๆ˜ฏๅฎŒๅ…จไธๅŒ็š„็–พ็—…๏ผš

็‰นๅพต NMOSD MS
็™ผ็—…ๆฉŸ่ฝ‰ AQP4-IgG ๅฐๆ˜Ÿๅฝข่† ็ดฐ่ƒž T-cell ๅฐ myelin
ๆ€งๅˆฅ ๅฅณ:็”ท ~ 9:1 ๅฅณ:็”ท ~ 3:1
ๆ—็พค ไบžๆดฒใ€้žๆดฒใ€ๆ‹‰ไธ่ฃ”่ผƒๅธธ่ฆ‹ ๅŒ—ๆญ่ก€็ตฑๆœ€้ซ˜
็™ผ็—…ๅนด้ฝก ่ผƒๆ™š (~ 40 ๆญฒ) ่ผƒๆ—ฉ (20-40 ๆญฒ)
่ฆ–็ฅž็ถ“็‚Ž ๅธธ้›™ๅดใ€ๅšด้‡ใ€ๅ่ฆ† ๅ–ฎๅดใ€ไธญๅบฆ
่„Š้ซ“็‚Ž ้•ท็ฏ€ๆฎต (โ‰ฅ 3 vertebral segments), ๅฎŒๅ…จๆฉซ่ฒซ ็Ÿญ็ฏ€ๆฎต, ้ƒจๅˆ†ๆ€ง
Area postrema ็—‡ๅ€™็พค ็‰นๅพตๆ€ง (้ ‘ๅ›บๅ˜”ๅ + ๆ‰“ๅ—) ็ฝ•่ฆ‹
OCB (CSF ๅฏกๆ ชๅธถ) < 30% ้™ฝๆ€ง > 90% ้™ฝๆ€ง
MRI ่…ฆ็—…็ถ ่ผƒๅฐ‘, ็‰นๅฎšไฝ็ฝฎ ๅคš, ๆ•ฃๅธƒ (Dawson fingers)
้ ๅพŒ ๅ–ฎๆฌก็™ผไฝœๅฏ้€ ๆˆๅšด้‡ๅคฑ่ƒฝ ็™ผไฝœๅพŒๅธธๆœ‰ๆขๅพฉ
ๆฒป็™‚ anti-C5, anti-CD19, anti-IL-6R, rituximab, MMF, AZA DMTs (interferon, anti-CD20, S1P, etc.)
ๅนฒๆ“พ็ด  / fingolimod / natalizumab ็ฆๅฟŒ๏ผๅฏ่ƒฝๆƒกๅŒ– ๆจ™ๆบ–ๆฒป็™‚
ๆŠ—้ซ” AQP4-IgG ~ 80% ้™ฝๆ€ง ็„ก็‰นๅฎš

้€™ๅฐฑๆ˜ฏ็‚บไป€้บผๅฟ…้ ˆๅœจๆ‡ท็–‘ MS ๆ™‚ๅ…ˆๆŽ’้™ค NMOSD๏ผ

388.1.0.1.3 NMOSD ่‡จๅบŠ่กจ็พ

388.1.1 6 ๅ€‹ๆ ธๅฟƒ่‡จๅบŠ่กจ็พ (Core Clinical Characteristics)

  1. ่ฆ–็ฅž็ถ“็‚Ž (Optic neuritis) โ€” ้€šๅธธๅšด้‡ (่ฆ–ๅŠ›ๆฅตๅทฎ / ๅคฑๆ˜Ž), ๅธธ้›™ๅดๆˆ–ๅ่ฆ†, ๆขๅพฉๅทฎ
  2. ๆ€ฅๆ€ง่„Š้ซ“็‚Ž (Acute myelitis) โ€” ๅฎŒๅ…จๆฉซ่ฒซๆ€ง, ้•ท็ฏ€ๆฎต LETM (โ‰ฅ 3 vertebral segments)
  3. Area postrema ็—‡ๅ€™็พค โ€” ้ ‘ๅ›บๆ€งๅ˜”ๅ / ๆ‰“ๅ— / ๅ™ๅฟƒ (ๆŒ็บŒๆ•ธๅคฉไปฅไธŠ)
  4. ๆ€ฅๆ€ง่…ฆๅนน็—‡ๅ€™็พค โ€” ่ค‡่ฆ–ใ€ๆง‹้Ÿณ้šœ็ค™ใ€ๅžๅšฅๅ›ฐ้›ฃใ€internuclear ophthalmoplegia
  5. ๆ€ฅๆ€ง้–“่…ฆ็—‡ๅ€™็พค โ€” ๅ—œ็กใ€้ซ”ๆบซ็•ฐๅธธใ€SIADHใ€narcolepsy ๆจฃ็—‡็‹€
  6. ๅคง่…ฆ็—‡ๅ€™็พค โ€” ่ผƒๅฐ‘, ไฝ†ๅฏ่ƒฝๆœ‰ๅคง็—…็ถ

388.1.2 ่‡จๅบŠ็‰น้ปž

  • ็™ผไฝœ้€šๅธธๅšด้‡ + ๆขๅพฉๅทฎ (่ˆ‡ MS ไธๅŒ)
  • ๅ่ฆ†็™ผไฝœ็ดฏ็ฉๅคฑ่ƒฝ
  • ๅคงๅคšๆ•ธๅพฉ็™ผๅž‹ (relapsing)
  • ๅฐ‘ๆ•ธๅ–ฎ็›ธ (monophasic)
  • ๆ—ฉๆœŸ็ฉๆฅตๆฒป็™‚้—œ้ต
388.1.2.0.1 NMOSD ่จบๆ–ท

388.1.3 2015 ๅœ‹้š›่จบๆ–ทๆจ™ๆบ– (Wingerchuk Criteria)

AQP4-IgG ้™ฝๆ€ง NMOSD๏ผš - โ‰ฅ 1 ๅ€‹ๆ ธๅฟƒ่‡จๅบŠ่กจ็พ - AQP4-IgG ้™ฝๆ€ง (็ดฐ่ƒž็‚บๅŸบ็คŽ็š„ๆธฌ่ฉฆ โ€” cell-based assay ็‚บไฝณ) - ๆŽ’้™คๅ…ถไป–ๅฏ่ƒฝ่จบๆ–ท

AQP4-IgG ้™ฐๆ€งๆˆ–ๆœชๆธฌ NMOSD๏ผš - โ‰ฅ 2 ๅ€‹ๆ ธๅฟƒ่‡จๅบŠ่กจ็พ (็ฉบ้–“ๆ•ฃๅธƒ) - ่‡ณๅฐ‘ 1 ๅ€‹ๆ˜ฏ่ฆ–็ฅž็ถ“็‚Žใ€้•ท็ฏ€ๆฎต่„Š้ซ“็‚Žใ€ๆˆ– area postrema ็—‡ๅ€™็พค - ๅ…ถไป–้กๅค– MRI ๆจ™ๆบ– - ๆŽ’้™คๅ…ถไป–

388.1.4 ้‡่ฆๅทฅๅ…ท

  • AQP4-IgG ๆŠ—้ซ” (cell-based assay ๆœ€ๆ•ๆ„Ÿ) โ€” ็ฏฉๆชขๅฟ…ๅ‚™
  • MOG-IgG โ€” ่‹ฅ AQP4 ้™ฐๆ€ง, ๆŽ’้™ค MOGAD
  • MRI: ่„Š้ซ“ LETM (โ‰ฅ 3 vertebral segments)ใ€่ฆ–็ฅž็ถ“ enhancementใ€็‰นๅฎš่…ฆ้ƒจไฝ็ฝฎ (area postrema, hypothalamus, periventricular surrounding 3rd/4th ventricles)
  • CSF: ็ดฐ่ƒž โ†‘ (ๅฏไปฅๅพˆ้ซ˜, > 50)ใ€่›‹็™ฝ โ†‘ใ€OCB ่ผƒๅฐ‘ (< 30%)
  • VEP ่ฆ–็ฅž็ถ“ๆๅ‚ท
388.1.4.0.1 NMOSD ๆฒป็™‚

388.1.5 ๆ€ฅๆ€ง็™ผไฝœ

  • ้ซ˜ๅŠ‘้‡ methylprednisolone 1 g IV ร— 5-7 ๅคฉ (ๆฏ” MS ไน…)
  • PLEX (plasma exchange) ๆ—ฉๆœŸ็ฉๆฅตไฝฟ็”จ โ€” ่ญ‰ๆ“šๅผท, ไธ่ฆ็ญ‰
  • IVIG ๆ›ฟไปฃ้ธๆ“‡

388.1.6 ้ ้˜ฒ (Maintenance) โ€” ้—œ้ต

388.1.6.1 FDA ๆ ธๅ‡† (NMOSD-specific)

  1. Eculizumab (Soliris) โ€” anti-C5 monoclonal, FDA 2019
    • PREVENT trial
    • ่ฃœ้ซ” 5 ๆŠ‘ๅˆถ โ†’ ้ ้˜ฒ AQP4-IgG ๅผ•่ตท็š„่ฃœ้ซ”ๅ‚ทๅฎณ
    • ้‡่ฆ่ญฆๅ‘Š: ่…ฆ่†œ็‚Ž้›™็ƒ่Œๆ„ŸๆŸ“้ขจ้šช โ†’ ๅฟ…้ ˆๅ…ˆๆ‰“็–ซ่‹— (MenACWY + MenB) ่‡ณๅฐ‘ 2 ้€ฑ
    • IV q2 weeks
    • ้ซ˜ๆ•ˆไฝ†้ซ˜ๅƒน
  2. Inebilizumab (Uplizna) โ€” anti-CD19 monoclonal, FDA 2020
    • ๆฎบ B ็ดฐ่ƒž + plasmablasts (B ็ดฐ่ƒž + ๆ—ฉๆœŸ plasma cells)
    • N-MOmentum trial
    • IV q6 months
  3. Satralizumab (Enspryng) โ€” anti-IL-6R monoclonal, FDA 2020
    • ๆŠ‘ๅˆถ IL-6 ่ทฏๅพ‘ (NMOSD ้‡่ฆ็ดฐ่ƒžๆฟ€็ด )
    • SAkuraSky + SAkuraStar trials
    • ็šฎไธ‹ๆณจๅฐ„ q4 weeks (ๅฑ…ๅฎถ)
  4. Ravulizumab (Ultomiris) โ€” anti-C5 monoclonal, FDA 2024
    • ้กžไผผ eculizumab ไฝ†็ตฆ่—ฅ้–“้š”่ผƒ้•ท (q8 weeks)
    • CHAMPION-NMOSD trial

388.1.6.2 Off-label (ๅ‚ณ็ตฑ้ธๆ“‡)

  • Rituximab โ€” anti-CD20, IV q6 months (ๆœ‰ๆ•ˆไฝ† off-label, ่ผƒไพฟๅฎœ)
  • Mycophenolate mofetil (MMF) โ€” ๅฃๆœๆฏๆ—ฅ
  • Azathioprine (AZA) โ€” ๅฃๆœๆฏๆ—ฅ
  • ้€šๅธธๅŠ ไธŠไฝŽๅŠ‘้‡ prednisone

388.1.6.3 ็ฆ็”จ๏ผ(ๆœƒๆƒกๅŒ– NMOSD)

  • Interferon-ฮฒ (ไปปไฝ•ๅฝขๅผ)
  • Fingolimod (Gilenya)
  • Natalizumab (Tysabri)
  • Alemtuzumab
  • ้€™ไบ›ๆ˜ฏ MS ๆฒป็™‚่—ฅ, NMOSD ็”จไบ†ๆœƒๆ›ด็ณŸ

388.1.6.4 ๆฒป็™‚้ธๆ“‡้‚่ผฏ

  • AQP4-IgG ้™ฝๆ€ง: ้ซ˜ๅบฆๆดป่บ โ†’ ๆ—ฉๆœŸไฝฟ็”จ FDA ๆ ธๅ‡†่—ฅ (eculizumab/ravulizumab/satralizumab/inebilizumab)
  • ่ผƒไธๆดป่บๆˆ–็ถ“ๆฟŸ่€ƒ้‡: rituximab off-label, MMF, AZA
  • ๅšด้‡็™ผไฝœ: PLEX + ้ซ˜ๅŠ‘้‡้กžๅ›บ้†‡
388.1.6.4.1 MOGAD (MOG Antibody-Associated Disease)

388.1.7 ๆœฌ่ณช

  • ๆŠ— myelin oligodendrocyte glycoprotein (MOG) ๆŠ—้ซ”้™ฝๆ€ง
  • MOG ๆ˜ฏ myelin ่กจ้ขๅˆ†ๅญ
  • ไธๅŒๆ–ผ MS, ไธๅŒๆ–ผ NMOSD
  • ่ผƒๅธธ่ฆ‹ๆ–ผๅ…’็ซฅใ€ๅนด่ผ•ๆˆไบบ

388.1.8 ่‡จๅบŠ่กจ็พ

  • ๆ€ฅๆ€งๆ•ฃๅธƒๆ€ง่…ฆ่„Š้ซ“็‚Ž (ADEM) โ€” ๅ…’็ซฅๅ…ธๅž‹
  • ่ฆ–็ฅž็ถ“็‚Ž (ๅธธ้›™ๅด, ่ฆ–็›ค่…ซ่„นๆ˜Ž้กฏ, ๆฏ” MS ๆ›ดๆ€ฅๆ›ดๅšด้‡)
  • ๆฉซ่ฒซๆ€ง่„Š้ซ“็‚Ž (ๅฏ้•ท็ฏ€ๆฎตๆˆ–็Ÿญ็ฏ€ๆฎต)
  • ่…ฆๅนน็—‡็‹€
  • ็šฎ่ณชๆ€ง่…ฆ็‚Ž (FLAMES โ€” FLAIR-hyperintense lesions in anti-MOG associated encephalitis with seizures)

388.1.9 ็—…็จ‹

  • ๅฏ่ƒฝๅ–ฎ็›ธ (monophasic, ~ 50%) ๆˆ–ๅพฉ็™ผๅž‹
  • ๅ…’็ซฅๅ‚พๅ‘ๅ–ฎ็›ธ
  • ๆˆไบบ่ผƒๅธธๅพฉ็™ผ
  • ้ ๅพŒ้€šๅธธ่ผƒ NMOSD ๅฅฝ (ๆขๅพฉ่ผƒๅฎŒๆ•ด)

388.1.10 ่จบๆ–ท

  • MOG-IgG (cell-based assay, ้ซ˜ titer ๆ‰ๆœ‰ๆ„็พฉ)
  • AQP4-IgG ้™ฐๆ€ง
  • ๅฝฑๅƒ + ่‡จๅบŠ

388.1.11 ๆฒป็™‚

  • ๆ€ฅๆ€ง: ้กžๅ›บ้†‡ + IVIG + PLEX
  • ้ ้˜ฒ (ๅ่ฆ† attacks ่€…): rituximab + MMF + IVIG (ๆฏๆœˆ) โ€” off-label
  • ๅ…’็ซฅ ADEM ๅ–ฎ็›ธ: ้€šๅธธไธ้œ€้•ทๆœŸ็ถญๆŒ
388.1.11.0.1 ADEM (Acute Disseminated Encephalomyelitis)

388.1.12 ๆœฌ่ณช

  • ๆ€ฅๆ€งใ€ๅ–ฎ็›ธใ€ๅคš็ถๆ€ง CNS ่„ซ้ซ“้ž˜
  • ๅธธๆ„ŸๆŸ“ๅพŒ (post-infectious) ๆˆ– ็–ซ่‹—ๅพŒ (post-vaccination)
  • ๅ…’็ซฅๅธธ่ฆ‹, ๆˆไบบไนŸๅฏ็™ผ็”Ÿ

388.1.13 ่กจ็พ

  • ็™ผ็‡’ใ€้ ญ็—›ใ€่…ฆ็—…ใ€ๅคš็ถๆ€ง็ฅž็ถ“็ผบๆ
  • ๅคš systemic involvement (่„Š้ซ“ใ€่…ฆๅนนใ€่ฆ–็ฅž็ถ“ใ€cerebral)
  • MRI: ๅคงใ€็€ฐๆผซๆ€งใ€ๅฐ็จฑๆ€ง็—…็ถ (ๅฅฝ็™ผ grey matter + thalamus + brainstem)

388.1.14 ๆฒป็™‚

  • ้ซ˜ๅŠ‘้‡้กžๅ›บ้†‡
  • IVIG ๆˆ– PLEX (้‡็—‡)
  • ๅคšๆ•ธๆขๅพฉ่‰ฏๅฅฝ

388.1.14.1 ๐Ÿฉบ ๅบŠ้‚Š้€ŸๆŸฅ

  • NMOSD โ‰  MS: AQP4-IgG, ๆฒป็™‚ๅฎŒๅ…จไธๅŒ
  • MS ๆจ™ๆบ–ๆฒป็™‚ (IFN, fingolimod, natalizumab) ๅœจ NMOSD ๅฏ่ƒฝๆƒกๅŒ–!
  • NMOSD 6 ๆ ธๅฟƒ: ่ฆ–็ฅž็ถ“็‚Ž + ่„Š้ซ“็‚Ž + area postrema + ่…ฆๅนน + ้–“่…ฆ + ๅคง่…ฆ
  • ๅฟ…ๆŸฅ: AQP4-IgG + MOG-IgG (cell-based assay)
  • NMOSD ๆ€ฅๆ€ง: methylprednisolone + ๆ—ฉๆœŸ PLEX
  • NMOSD ้ ้˜ฒ (FDA ๆ ธๅ‡†): eculizumab + ravulizumab + inebilizumab + satralizumab
  • NMOSD off-label: rituximab + MMF + AZA
  • Eculizumab ่ญฆๅ‘Š: ๅฟ…้ ˆๅ…ˆๆ‰“่…ฆ่†œ็‚Ž้›™็ƒ่Œ็–ซ่‹—
  • MOGAD: MOG-IgG ้™ฝๆ€ง, ADEM/่ฆ–็ฅž็ถ“็‚Ž/่„Š้ซ“็‚Ž, ๆฒป็™‚้กžๅ›บ้†‡ + IVIG + PLEX + ้ ้˜ฒ rituximab/MMF/IVIG
  • ADEM: ๆ„ŸๆŸ“ๅพŒ / ็–ซ่‹—ๅพŒ, ๅ–ฎ็›ธ, ๅ…’็ซฅๅธธ่ฆ‹