Espectro da neuromielite óptica: uma revisão com ênfase em crianças e adolescentes

Paolilo, Renata Barbosa; Paz, José Albino da; Apóstolos-Pereira, Samira Luisa; Rimkus, Carolina de Medeiros; Callegaro, Dagoberto; Sato, Douglas Kazutoshi

Renata Barbosa Paolilo Address for correspondence Renata Barbosa Paolilo (email: renatabpaolilo@gmail.com).

conceptualization

methodology

visualization

writing - original draft

review and editing

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil

https://orcid.org/0000-0003-3548-8467

José Albino da Paz

review and editing

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil

https://orcid.org/0000-0003-4977-099X

Samira Luisa Apóstolos-Pereira

review and editing

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil

https://orcid.org/0000-0003-3493-1199

Carolina de Medeiros Rimkus

review and editing

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Radiologia, São Paulo SP, Brazil

https://orcid.org/0000-0002-3866-1299

Dagoberto Callegaro

review and editing

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil

https://orcid.org/0000-0003-0077-173X

Douglas Kazutoshi Sato

conceptualization

methodology

validation

review and editing

Pontifícia Universidade Católica do Rio Grande do Sul, Instituto do Cérebro do Rio Grande do Sul, Porto Alegre RS, Brazil

https://orcid.org/0000-0002-7695-6020

Address for correspondence Renata Barbosa Paolilo (email: renatabpaolilo@gmail.com).

Conflict of Interest

The authors declare that there are no conflicts of interest related to this study. RBP: reports grants from Roche and Merck and speaker honoraria from Novartis, outside the submitted work; JAP: nothing to disclose; SLAP: reports grants, preceptorships and research support from Genzyme, Roche, Novartis, Merck-Serono, and Biogen, outside the submitted work; CMR: reports speaker honoraria from Roche and the Brazilian Committee for Treatment and Research of Multiple Sclerosis, outside the submitted work; DC: reports grants, preceptorships, and research support from Genzyme, Roche, Novartis, Merck-Serono, Teva and Biogen, outside the submitted work; DKS: reports grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - Brazil (425331/ 2016-4), grants from Fundação e Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) - Brazil, grants and personal fees from TEVA and Merck, personal fees from Biogen, Roche, and Viela Bio, outside the submitted work.

Medications

Dose

Adverse effects

Precautions

Azathioprine

2–3mg/kg/day, oral Once a day

Myelotoxicity and hepatotoxicity

-Check vaccinations and infection risks (including tuberculosis) before initiation. Avoid live vaccines.

-Laboratory control to check myelotoxicity and hepatotoxicity monthly for 3 months and then every 3–6 months.

-Tapper oral steroids after 3–6 months.

-Contraception.

Mycophenolate mofetil

10–12,5mg/kg/day, oral (750–3,000mg/day) Twice a day

Myelotoxicity

-Check vaccinations and infection risks (including tuberculosis) before initiation. Avoid live vaccines.

-Laboratory control to check myelotoxicity and hepatotoxicity monthly for 3 months and then every 3–6 months.

-Tapper oral steroids after 3 months.

-Contraception.

Rituximab

If child < 40kg or < 12 years old:

-First infusion: 375mg/m2/ dose, 4 doses, weekly

-Subsequent infusions: 375mg/m2/dose, 2 doses, biweekly

If child ≥ 40kg or ≥ 12 years-old:

-First infusion: 1 g/dose, 2 doses, weekly

-Subsequent infusions: 1 g/dose

Repeat every 6 months or according to B cell repopulation evidence

Infusion allergies

Hypoimmunoglobulinemia

Hepatitis B reactivation

-Check vaccinations (specially hepatitis B vaccine) and infection risks (including tuberculosis) before initiation. Avoid live vaccines.

-Pretreatment prior to infusion with antihistamines, antipyretics and corticosteroids

-CD19 control at 2,4, and 6 months.

-Laboratory control with cell blood count, IgG, IgM, and IgA every 3 months.

-Contraception.

Author, Year, Country	Diagnostic criteria	Number of patients	Age at onset, years ± SD (range)	Gender F:M	Non-white ethnicity	Recurrent course	ARR	AQP4-lgG (Assay)	MOG-IgG	Follow-up, years (range)	EDSS Last visit
Camera, 2021 United Kingdom	2015	49	1 2 ± 4,1	7:1	61.2%	83.7%	0.31	100% (CBA)	NR	6.6 (0.2-33.4)	NR
Paolilo, 2020 Brazil \| Europe	2015	67	10.2 ± 3,6(2-16)	4,1:1	56.7%	86.6%	1.05	100% (CBA)	0/67	4(2-10)	2.0 (1-3.5)
Lechner, 2020 Germany \| Austria	2015	24	11 (3-17)	2.7:1	45.8%	NR	NR	67% (CBA)	16.7%	NR	NR
Zhou, 2019^a China	2015	33	6.8 (4,2-8,7)	1.5:1	NR	NR	NR	30% (NR)	55%	NR	NR
Dahan, 2019 Australia	2015	5	12.2 (6-15)	1:1,5	40%	60%	NR	20% (CBA)	40%	3 (±1.6)	1.0 (0-1)
Zhou, 2019 China	2015 2006	31	14 (7-17)	4.2:1	NR	94%	0.73	74.1% (CBA)	9.7%	2 (0.3-14.5)	1.5(0-7)
Fragoso, 2019 Brazil	2015	27	1–17	3.8:1	48.1%	NR	NR	15/23 (65.2%) (IFI)	0/9	6(1-34)	3.0 (0-10)
Baghbanian, 2019 Iran	2015	10	13 (8-17)	4:1	NR	100%	NR	7 (CBA)	NR	NR	2.5
Sepulveda, 2018 Spain	2015	5	-	1.5:1	NR	NR	NR	40% (CBA)	60%	NR	NR
Boesen, 2018 Denmark	2015	5	12.2 (2.8-14.8)	1:4	NR	NR	NR	NR	NR	4.6 (0.3-9.4)	NR
Fragomeni, 2018 Brazil	2015 2006	12	14 (5.1-17)	2.6:1	46.5%	NR	1.5 (±1.8)	72.5% (IFI)	NR	6.7	4
Hacohen, 2017 United Kingdom	2015	28	8 (5-11)	2.5:1	53.5%	100%	NR	28.6% (CBA)	57.7%	4(3-6.7)	1 (0-2)
Yamaguchi, 2016 Japan	2006	10	9.5 (3-15)	4:1	100%	90%	0.66	30% NR	NR	6.3	NR
Chitnis, 2016 United States of America	2013 2015	38	10.2 (16m-17)	2.1:1	63.1%	NR	NR	65% NR	NR	2	2.25
Lechner, 2016 Germany \| Austria	2006	12	NR	NR	NR	NR	NR	25% NR	NR	NR	NR
Absoud, 2015 United Kingdom	2006	20	10.5 (2.9-16,8)	9:1	NR	90%	NR	60% NR	NR	6.1	NR
Fragoso, 2014 Brzsil	2006	29	13 (5-17)	2.6:1	58.6%	NR	0.75	78% (IFI)	NR	NR	4.7 (± 2.7)
Rostasy, 2012 Europe	2006	8	11 (± 6)	6.2:1	NR	87.5%	NR	25% (CBA)	38%	NR	NR
Pena, 2011 Venezuela	2006 2007	6	5-13	5:1	100%	100%	0.75	80% NR	NR	NR	NR
Collonges, 2010 France	2006	12	14.5 (4.1-17.9)	3:1	33.3%	NR	0.6	66.7% NR	NR	19.3	NR
Huppke, 2010 Germany	2006	6	12 (3-17)	2:1	33.3%	50%		17% NR	NR	3	NR
Banwell, 2008 Canada / Argentina	1999	17	10.4 (4.4-15.2)	3.2:1	31%	52.9%	NR	47% NR	NR	1.1 a 4.95	2.5 (0-8)
Lotze, 2008 United States of America	2007	9	14 (1.9-16)	9:0	77.7%	100%	NR	78% NR	NR	4	NR
McKeon, 2008 United States of America	2006	58	12 (4-18)	2.6:1	73%	93%	NR	100% (IFI)	NR	1	4

[1] Address for correspondence Renata Barbosa Paolilo (email: renatabpaolilo@gmail.com).

Positive AQP4-IgG	1. At least one clinical syndrome 2. Positive AQP4-IgG by the best assay 3. Exclusion of alternative diagnosis
Negative or unknown AQP4-IgG	1. At least two clinical syndromes - at least one must be: Optic Neuritis, LETM or area postrema syndrome - evidence of dissemination in space - fulfill additional MRI criteria 2. Negative AQP4-IgG by the best assay or unavailable antibody testing 3. Exclusion of alternative diagnosis
Clinical syndromes	1. Optic neuritis 2. Acute myelitis 3. Area postrema syndrome 4. Brainstem syndrome 5. Diencephalic syndrome 6. Cerebral syndrome
Additional MRI criteria	1. Acute optic neuritis - normal brain MRI or unspecific findings, or - optic nerve MRI with T2-hyperintensive lesion or gadolinium enhancement extending over > ½ optic nerve length or involving optic chiasm 2. Acute myelitis -intramedullary lesion extending over ≥ 3 contiguous segments (LETM), or -spinal cord atrophy ≥ 3 segments in a patient with history compatible with acute myelitis 3. Area postrema syndrome: dorsal medula/area postrema lesions 4. Acute brainstem syndrome: periependymal brainstem lesions

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Espectro da neuromielite óptica: uma revisão com ênfase em crianças e adolescentes

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