1. Optic nerve and chiasmatic-hypothalamic tumors

2. J. Francisco Salomão Section of Pediatric Neurosurgery – Dept. of Pediatric Surgery Fernandes Figueira Institute (Oswaldo Cruz Foundation - Fiocruz) Rio de Janeiro, R.J. Rio de Janeiro, R.J.Brazil

3. Gliomas

4. OPT 3-6% of pediatric intracranial tumors 75% in the first decade of life 15-20% of CNS astrocytomas No gender predominance

5. OPT - Classification Prechiasmatic Exophitic Diffuse Prechiasmatic Chiasmatic-hypothalamic

6. Histopathology Pilomixoid astrocytoma (Tihan et al, 1999) Astrocytic tumors 1.1.1 Astrocytoma - Fibrilary, protoplasmátic, gemystocític 1.1.2 Anaplastic astrocytoma (malignant) GCGB, Gliosarcoma 1.1.3 Multiform gliblastomas 1.1.4Pilocytic astrocitoma 1.1.5Pleomorphic xantoastrocitoma 1.1.6GCSA(Tuberous sclerosis)

7. OPT Diagnostic criteria of NF1 National Institutes of Health consensus statement on neurofibromatosis (1987) 1. Six or more café-au-lait macules larger than 5mm in greatest diameter in prepubertal individuals and larger than 15 mm in postpubertal individuals; 2. Two or more neurofibromas of any type or one plexiform neurofibroma; 3. Freckling in the axilary or inguinal region; 4. Optic glioma; 5. Two or more Lisch nodules (iris hamartomas); 6. A distinctive osseous lesion (eg, sphenoid dysplasia or thinning of long bone cortex with or without pseudoarthrosis); 7. A first degree relative (parent, sibling, or offspring) with neurofibromatosis 1 according the above criteria. (Two or more criteria are needed for a diagnosis of NF1) Neurofibromatosis 1 Sporadic

8. OPT and NF1 Orbital optic nerve 50-75% of patients have NF1 Multicentric tumors Asymptomatic Indolents Proptosis / visual deficit Sporadic OPT Chiasm and hypothalamus 10 % NF1 Isolated Aggressive IC hypertension

9. OPT and NF1 “ OPG in patients without NF differs significantly from NF- OPG in both imaging features and prognosis. Non NF- OPG and NF-OPG are apparently distinct entities, each warranting a specific diagnostic, clinical and therapeutic approach.” Kornreich L et al., 2001

10. Optic nerve glioma (ONG) Proptosis Painless Non pulsatile Visual loss Optic atrophy/ papilledema Decreased eye movements

11. ONG

12. Surgical indications Loss of unilateral vision (blindness) Progressive visual loss Exophtalmos Surgical contraindications Partially preserved vision Moderate proptosis Stable lesions Contralateral extension or chiasmal envolvement

13. ONG

15. Chiasmatic-hypothalamic tumors (Ch-H)

16. Ch-H

18. Signs and symptoms Chiasmatic Hypothalamic

19. Ch-H tumors : Problems in management Natural history and course Number of patients Variability of treatment options Lack of prospective of studies Biologic behavior What is the best treatment ?

20. Ch-H – Options of treatment Observation Stable lesions NF1 Surgery Radical subtotal Limited  Decompression  Biopsy Chemotherapy Radiation therapy

21. Surgery – Subtotal removal Hoffman, 1983 Albrighth & Selabassi, 1985 Fletcher et al., 1986 Wisoff, 1990

22. Surgery – Subtotal removal

25. Operative morbidity and morbidity Diabetes insipidus Hypersomnia Amaurosis Precocious puberty ADH ISS Death

26. Limited surgery + Chemotherapy 6m1y

27. Limited surgery + Chemotherapy Before (02/1998) ) After (05/2000 )

28. Biopsy + Chemotherapy

29. Current trends Avoid radiation therapy Delay radiation therapy

30. Radiation therapy Intelectual impairment Visual impairment Endocrine impairment Moyamoya disease Brain infarction Induced tumors Relapse Older children

31. Chemotherapy + Radiation therapy1997 1999 2000 2002 RT 2004

32. Outcome : Factors affecting long-term survival Increasing age NF1 Chemotherapy Radiation therapy 69% 10y PFS Grabenbauer et al., 2000 Chemotherapy 34% 5y PFS 89% 5y OS 61% 5y RT FS Laithier et al., 2003

33. OPT are a puzzle 1994 19952002

34. OPT are a puzzle

36. OPT - Conclusions 1. OPT have an unpredictable course despite histological benignity; 2. Tumors associated with NF1 have a most favorable outcome; 3. Age is the most important prognostic factor and younger children have the worst prognosis; 4. Unilateral ONGs associated with blindness and proptosis are best treated with radical resection; 5. Subtotal radical surgery of Ch-H tumors is feasible but is associated with a high morbidity; 6. Chemotherapy seems to be a reasonable alternative as first line treatment of Ch-H tumors; 7. Prospective, randomized, multicentric studies are needed in order to know the natural history and define the best treatment of OPT.