387.4 ๐ ็ซ ๆซ้่จ Summary
387.4.1 ๐ ไธๅฅ่ฉฑ็ธฝ็ต
ๅค็ผๆง็กฌๅ็ (MS) ๆฏไธญๆจ็ฅ็ถ็ณป็ตฑ (CNS) ็ๆ ขๆง็ผ็ๆงใ่ซ้ซ้ๆงใ็ฅ็ถ้ๅๆง็พ็ ; ่ด็ ๆฉ่ฝๆฏ่ช้ซๅ ็ซๆปๆ myelin โ ่ปธ็ดขๆๅท โ ็ฅ็ถ้ๅ; ็ผ็ ้ซๅณฐ 20-40 ๆญฒ + ๅฅณ:็ท ~ 3:1 + ๅๆญ่ก็ตฑ้ซ็ผ + ๅฐ็ฃ็่ก็็ด 5/10 ่ฌ (็ธๅฐไฝ); ้่ฆ็ฐๅขๅฑ้ชๅ ๅญ โ Bjornevik 2022 NEJM ้กฏ็คบ EBV ๆๆๆฏ MS ๅฟ ่ฆๆขไปถ (ไฝไธๅ ๅ) + ็ถญ็็ด D ็ผบไน + ๆฝ่ธ + ็ซฅๅนด/้ๅฐๅนด่ฅ่ + ้ซ็ทฏๅบฆ; ่จๅบๅๆ โ (1) ๅพฉ็ผ็ทฉ่งฃๅ (RRMS) ~ 85% ๆๅธธ่ฆ โ ๆฅๆง็ผไฝๅพๅฏ้จๅๆๅฎๅ จๆขๅพฉ, ็ผไฝ้ๆ็ฉฉๅฎ, ๅคๆธๆๅพ้ฒๅ ฅ SPMS, (2) ็บ็ผ้ฒ่กๅ (SPMS) โ RRMS ๆผ่ฎ (10-20 ๅนดๅพ), ้ฒ่กๆงๆกๅ, (3) ๅ็ผ้ฒ่กๅ (PPMS) ~ 10-15% โ ไธ้ๅงๅฐฑๆ ขๆ ขๆกๅ, ่้ซ็็็บไธป, ็ทๅฅณๆฏไพ ~ 1:1, ็ผ็ ่ผๆ ~ 40-50 ๆญฒ, (4) ่จๅบๅญค็ซ็ๅ็พค (CIS) โ ้ฆๆฌก็ผไฝๆช็ขบ่จบ, (5) ๆพๅฐๅญค็ซ็ๅ็พค (RIS) โ ๅฝฑๅ only; ๅธธ่ฆ็็ โ ่ฆ็ฅ็ถ็ (ๆๅธธ่ฆๅๅง โ ๅฎๅด็ผ็ + ่ฆๅไธ้ + ่ฒๅฝฉ้ฃฝๅๅบฆไธ้ + ไธญๅคฎ่ฆ้็ผบๆ + RAPD/Marcus Gunn pupil + ่ฆ็คๅฏ่ฝๆญฃๅธธ็ๅพ / ๅคๆธ 1-3 ๆๆขๅพฉ) + ่้ซ็ (้จๅๆง + ็ญ็ฏๆฎต < 3 vertebral segments โ ๅฐๆฏ NMOSD ้ท็ฏๆฎตๅฎๅ จๆฉซ่ฒซ) + ่ ฆๅนน็็ (่ค่ฆ + ๆ็ฉ + ไธๅ็ฅ็ถ็ โ ๅนด่ผไธๅ็ฅ็ถ็่ฆๆณ MS! + ๆง้ณ้็ค + ๅๅฅ) + ๅฐ่ ฆ็็ (ๅ ฑๆฟๅคฑ่ชฟ) + INO (internuclear ophthalmoplegia โ ๅ งๅด็ธฑๆๆๅท, ็ๅๅๅดๆๅฐๅดๅ งๆถๅ้ + ๅๅดๅคๅฑ็ผ้, MS ๅ ธๅ, ้ๅด INO ๅนพไนไธๅฎ MS) + Lhermitte ๅพต (้ ธๅฝๆฒๆ้ปๆๆๆฒฟ่ๆฑๆพๅฐ, ้ ธๆฎตๅพๆฑๅๆ, ไน่ฆๆผ้ ธๆค็ ่ฎ/B12 ็ผบไน) + Uhthoff ็พ่ฑก (้ซๆบซไธๅๆ็็ๆซๆๆกๅ, ๅป้ซ้ๅฐๆบซๅบฆๆๆ) + ็ฒๅฆ (fatigue ๆๅธธ่ขซๅๅ ฑ, ๅฝฑ้ฟ็ๆดปๅ่ณช) + ่ช็ฅๅ่ฝไธ้ (ๅท่กใๆณจๆๅใ่็้ๅบฆ, ~ 50%) + ็ๆฃ + ่่ฑ/่ ธ/ๆงๅ่ฝ้็ค + ๆ้ฌฑ (่ชๆฎบ้ขจ้ช้ซ!) + ไธญๅคฎๆง็ผ็ + ๅๆง็ผไฝ (true vs pseudo-relapse from ๆๆ/็ผ็); ่จบๆท McDonald 2017 ๆจๆบ โ ๆ ธๅฟๆฏ ๆ้ๆฃๅธ (DIT) + ็ฉบ้ๆฃๅธ (DIS) ็ๅฎข่ง่ญๆ; DIS โ ็ ็ถๅจ โฅ 2 ๅๅ ธๅ้จไฝ (็ฎ่ณชไธ/็ฎ่ณช + ่ ฆๅฎคๅจๅ + ๅนไธ + ่้ซ); DIT โ ไธๅๆ้็ๅ ฉๆฌก่จๅบ็ผไฝ OR MRI ๅๆ็ๅฐ enhancing + non-enhancing ็ ็ถ OR ่ฟฝ่นค MRI ๅบ็พๆฐ็ ็ถ OR CSF OCB ้ฝๆงๅฏๆฟไปฃ DIT (2017 ๆฐๅข); MRI ๆฏ่จบๆทไธปๅ โ ่ ฆ MRI ็ T2/FLAIR ้ซ่จ่ + โDawson fingersโ (่ ฆๅฎคๅจๅ, ่้ท่ปธๅ็ด) + juxtacortical + infratentorial; ่้ซ MRI ็ญ็ฏๆฎต้จๅๆง; Gd-enhancing ็ ็ถ้กฏ็คบๆดปๅๆง; CSF โ ๅฏกๆ ชๅ ็ซ็่็ฝๅธถ (Oligoclonal bands, OCBs) > 90% MS ๆฃ่ ้ฝๆง (CSF ๆไฝ่กๆธ ๆฒๆ) + IgG index โ + ็ดฐ่ๆธ่ผๅบฆไธๅ; Evoked potentials โ VEP (visual EP) ่ฆ็ฅ็ถๆๅท + BAEP + SSEP; ๅฟ ๆ้คๅ ถไปๅๅ (CRITICAL!): AQP4-IgG (NMOSD!) + MOG-IgG (MOGAD!) โ ๆฒป็็ญ็ฅๅฎๅ จไธๅ, MS ๆจๆบๆฒป็ (IFN, fingolimod, natalizumab) ๅจ NMOSD ๅฏ่ฝๆกๅ! + B12 + folate + ้ + ANA + HIV + syphilis; ๆฒป็ๆฅๆง็ผไฝ (relapse) โ methylprednisolone 1 g IV daily ร 3-5 days (ๅ ้ๆขๅพฉ, ไธๆน่ฎ้ทๆ้ ๅพ) + plasma exchange (PLEX) 5-7 ๆฌก if ้กๅบ้็กๆๆๅด้; DMT (disease-modifying therapy) ้ฉๅฝ 2020-2024 โ (1) ไฝ-ไธญๆๅๆณจๅฐๅ โ interferon-ฮฒ (Avonex/Rebif/Betaseron/Plegridy ๆตๆๆจฃ) + glatiramer acetate (Copaxone/Glatopa, ๆฏๆฅ็ฎไธ, ๆณจๅฐ้จไฝๅๆ); (2) ไธญ-้ซๆๅๅฃๆ โ teriflunomide (Aubagio, ่ๆฏๆง) + dimethyl fumarate (Tecfidera) + diroximel fumarate (Vumerity) (ๆฝฎ็ด + GI + ๆทๅทด็ไฝ + PML ้ขจ้ช) + S1P modulators (fingolimod Gilenya โ ้ฆๅๅฃๆ, ๅฟๅพ็ฃๆธฌ first-dose 6 hr, ้ปๆๆฐด่ ซ, PML; siponimod Mayzent for SPMS; ozanimod Zeposia better cardiac; ponesimod Ponvory short half-life) + cladribine (Mavenclad, purine analogue ็ญๆ + ๆไน ๆๅ + ๆทๅทด็ๆธๅฐ); (3) ้ซๆๅๆณจๅฐ/่ผธๆถฒ โ natalizumab (Tysabri anti-ฮฑ4 integrin IV monthly, PML ้ขจ้ช JC virus ๅฟ ๆฅ JCV antibody) + ocrelizumab (Ocrevus anti-CD20 IV q6 months, ้ฆๅ FDA ๆ ธๅ PPMS, ้ฉ็จ RRMS + PPMS) + ofatumumab (Kesimpta anti-CD20, ็ฎไธๆฏๆๅฑ ๅฎถๆฝๆ) + ublituximab (Briumvi anti-CD20, shorter infusion FDA 2022) + alemtuzumab (Lemtrada anti-CD52, ็ญๆ IV ้ซๆไฝๅด้ AE โ autoimmune diseases ITP/Goodpasture/Graves + infusion reactions + malignancy, ็ฌฌไธ็ท); ๆฉๆ high-efficacy ๆฒป็็ๅฟต โ treat early + treat hard ๆน่ฎ้ ๅพ; ่ช้ซๅนน็ดฐ่็งปๆค (AHSCT) โ MIST trial 2019 JAMA ้กฏ็คบๅชๆผ DMTs ๅฐ้ซๆดป่บๆง RRMS ๅฐ DMTs ็กๅๆ่ ; PPMS ๆฒป็ โ ocrelizumab ๅฏไธ FDA ๆ ธๅ, ๅ ถไป DMT ๅฐ PPMS ๆๅๆ้; ๅฐ็ๆฒป็ โ ็ๆฃ baclofen (ๅฃๆๆ้ๅ ง) + tizanidine + gabapentin + cannabinoids + botulinum; ่่ฑๆฅ่ฟซ oxybutynin/mirabegron; ๆปฏ็่ชๆๅฐๅฐฟ; ็ฒๅฆ amantadine + modafinil + ้ๅ; ็ผ็ ไธๅ็ฅ็ถ็ carbamazepine + ไธญๅคฎๆง gabapentinoids/TCAs/SNRIs; ๆ้ฌฑ SSRIs (ๆณจๆ่ชๆฎบ้ขจ้ช!); ่ตฐ่ทฏ dalfampridine (Ampyra) ้้้้ปๆทๆนๅ่ก่ตฐ้ๅบฆใ
387.4.2 ๐ ๆฒป็็ฒพ่ฆ
- ๆฅๆง็ผไฝ (relapse)๏ผๆ้ค pseudo-relapse โ methylprednisolone 1 g IV daily ร 3-5 days (ๅ ้ๆขๅพฉ) โ if ๅด้ๆ้กๅบ้็กๆ plasma exchange (PLEX) 5-7 ๆฌก
- DMT ้ธๆๅบๆผ disease activity + ้ ๅพๅ ๅญ + ็ ไบบๅๅฅฝ: ๆฉๆ็ฉๆฅต (treat early + treat hard) ๆนๅ้ทๆ้ ๅพ
- First-line for ไธญๅบฆๆดป่บ RRMS: oral S1P modulator (ozanimod, ponesimod), DMF, cladribine
- First-line for ้ซๅบฆๆดป่บ RRMS (้ ๅพไธ่ฏๅ ๅญ: ๅนด่ผ + ๅค็ผ + ้ๅๆๆฌ็ด่ + ่้ซ็ ็ถ + MRI ่ฒ ่ท้ซ): anti-CD20 (ocrelizumab IV q6 mo, ofatumumab SC monthly, ublituximab) + natalizumab + cladribine + AHSCT ่ๆ ฎ
- PPMS: ocrelizumab ๅฏไธ FDA ๆ ธๅ (Ch386-ๅฏไธ)
- Natalizumab ไฝฟ็จๅ: ๆฅ JCV antibody โ JCV negative ่ผๅฎๅ จ, JCV positive > 2 ๅนด้ซ PML ้ขจ้ช ~ 1/100; ๅๆๆ wash-out ไธ่ถณๆ rebound activity
- Anti-CD20 ๆณจๆ: HBV reactivation ็ฏฉๆชข + immunoglobulin ็ฃๆธฌ + ๆๆ้ขจ้ช
- Pregnancy: ๆทๅญๆ relapse ๆธๅฐ, ็ขๅพๅขๅ ; glatiramer + interferon ๅฏ็นผ็บ (ๅณ็ตฑ้ธๆ); ๆฐ DMTs ๅคงๅค้ๅ; anti-CD20 ็ตฆ่ฅๅ 6 ๅๆๅๅฏ่ๆ ฎ
- ๅฐ็ๆฒป็: ็ๆฃ โ baclofen ๅฃๆ 5-80 mg/d ๆ intrathecal pump + tizanidine + gabapentin + botulinum toxin; ่่ฑๆฅ่ฟซ โ oxybutynin + mirabegron + Botox; ็ฒๅฆ โ amantadine 200 mg/d + modafinil 100-400 mg/d; ็ผ็ โ ไธๅ็ฅ็ถ็ carbamazepine 200-1200 mg/d; ่ตฐ่ทฏๅฐ้ฃ โ dalfampridine 10 mg BID (Ampyra) ้้้้ปๆท
- AHSCT: ้ซๆดป่บๆง RRMS ๅฐ DMTs ็กๅๆ่ (MIST trial 2019)
387.4.3 ๐ฏ ็ง้ซๅธซ็่ๅๆ้
- MS ๆฏ CNS ๆ ขๆง็ผ็ๆง่ซ้ซ้ๆง็พ็ , 20-40 ๆญฒ็ผ็ , ๅฅณ:็ท 3:1; ้่ฆๅฑ้ชๅ ๅญ โ EBV (Bjornevik 2022 NEJM ้กฏ็คบ็บๅฟ ่ฆๆขไปถ, ้ขจ้ชไธๅ 32 ๅ) + ็ถญ็็ด D ็ผบไน + ๆฝ่ธ + ็ซฅๅนด่ฅ่
- ่จๅบๅๆ : RRMS 85% ๆๅธธ่ฆ (็ผไฝ โ ็ทฉ่งฃ) + SPMS (RRMS ๆผ่ฎ) + PPMS 10-15% (ไธ้ๅงๅฐฑๆผธ้ฒๆกๅ, ่้ซ็บไธป, ocrelizumab ๅฏไธ FDA ๆ ธๅ)
- ๅธธ่ฆ็็: ่ฆ็ฅ็ถ็ๆๅธธ่ฆๅๅง็็ (ๅฎๅด็ผ็ + ่ฆๅไธ้ + ่ฒๅฝฉ้ฃฝๅๅบฆ + RAPD) + ่้ซ็ (้จๅๆง + ็ญ็ฏๆฎต, ๅฐๆฏ NMOSD ้ท็ฏๆฎตๅฎๅ จๆฉซ่ฒซ) + INO (ๅ ๅด็ธฑๆ, MS ๅ ธๅ, ้ๅดๅนพไนไธๅฎ MS) + ไธๅ็ฅ็ถ็ (ๅนด่ผๆฃ่ โ ่ฆๆณ MS!) + Lhermitte (้ ธๅฝๆฒ้ปๆๆ) + Uhthoff (็ฑ่ช็ผ) + ็ฒๅฆ + ่ช็ฅ + ็ๆฃ + ่่ฑ
- ่จบๆท McDonald 2017: ๆ้ๆฃๅธ (DIT) + ็ฉบ้ๆฃๅธ (DIS) ๅฎข่ง่ญๆ; MRI ๆฏไธปๅ (Dawson fingers + juxtacortical + infratentorial + ่้ซ); CSF OCB > 90% MS ้ฝๆง + ๅฏๆฟไปฃ DIT (2017 ๆฐๅข)
- ๅฟ ๆ้ค NMOSD (AQP4-IgG) + MOGAD (MOG-IgG) โ ๆฒป็็ญ็ฅๅฎๅ จไธๅ, MS ๆจๆบๆฒป็ (IFN, fingolimod, natalizumab) ๅจ NMOSD ๅฏ่ฝๆกๅ!
- ๆฅๆง relapse ๆฒป็: ๆ้ค pseudo-relapse (ๆๆ/็ผ็) โ methylprednisolone 1 g IV ร 3-5 days โ PLEX 5-7 ๆฌก if ๅด้ๆ้กๅบ้็กๆ
- DMT ้ฉๅฝ 2020-2024: ้ซๆๅๆณจๅฐๅ โ anti-CD20 (ocrelizumab IV q6 mo + ofatumumab SC monthly ๅฑ ๅฎถ + ublituximab shorter infusion FDA 2022) + natalizumab (anti-ฮฑ4, JCV antibody ๆฅ PML ้ขจ้ช) + alemtuzumab (anti-CD52 ้ซๆไฝๅด้ AE); ๅฃๆ โ S1P modulators (fingolimod/siponimod/ozanimod/ponesimod) + cladribine (็ญๆๆไน ) + DMF/DRF + teriflunomide
- PPMS ๆฒป็: ocrelizumab ๅฏไธ FDA ๆ ธๅ (anti-CD20 IV q6 months)
- Natalizumab + PML ้ขจ้ช: JC virus + ๅฟ ๆฅ JCV antibody + JCV positive > 2 ๅนด PML ้ขจ้ช ~ 1/100; PML ๆญปไบก็้ซ
- ๅฐ็ๆฒป็: ็ๆฃ baclofen + ่่ฑๆฅ่ฟซ oxybutynin/mirabegron + ็ฒๅฆ amantadine/modafinil + ไธๅ็ฅ็ถ็ carbamazepine + ่ตฐ่ทฏ dalfampridine (Ampyra) ้้้้ปๆท + ๆ้ฌฑ SSRIs (ๆณจๆ MS ่ชๆฎบ้ขจ้ช้ซ!)