PEDIATRIC OPTIC PATHWAY GLIOMA: DIENCEPHALIC SYNDROME

Diencephalic cachexia (DC ) is a metabolic disorder characterized by a decrease in body weight. DC usually occurs in the presence of glioma brain tumors extended into the optic pathway. These tumors are very aggressive and have poor prognosis.

Objective: to analyze the clinical course of optic pathway gliomas (OPG s) in patients with and without DC .

Material and Methods. The study included 264 patients aged 0 to 18 years with an initial diagnosis of OPG s registered in the N.N. Burdenko National Medical Research Center of neurosurgery from 01/01/2003 to 12/31/2015. Patients were divided into two groups: without DC (204 people) and with DC (60 children).

Results: neurofibromatosis type I (NFI) was much more common in children without DC , and pilomyxoid histology was much more prevalent in children with DC . Five-year overall survival (OS ) and event-free survival EFS were significantly lower in children with DC than in children without DC (82 ± 5 % and 96 ± 1 %, respectively versus 37 ± 7 % and 62 ± 3 %, respectively). It was found that in the DC group, the OS and EFS rates were significantly lower in girls, in children without NFI, in children without histological verification and in children with pilocytic astrocytomas. It was also found that in the DC group, OS rates were significantly lower in children under 1 year, and EFS rates were significantly lower in children aged more than 12 months. The number of patients without events were significantly higher in the group without DC (p=0.001). The number of deaths in the postoperative period was significantly higher in children with DC (p<0.001). Diabetes insipidus and hyponatremia were significantly more common in patients with diencephalic cachexia, and vision improvement after treatment was significantly more likely to occur in patients without DC .

Conclusion. OPG s in patients with DC have a more aggressive clinical course, which requires more careful treatment and observation. 

1. Opocher E., Kremer L.C., Da Dalt L., van de Wetering M.D., Viscardi E., Caron H.N., Perilongo G. Prognostic factors for progression of childhood optic pathway glioma: a systematic review. Eur J Cancer. 2006 Aug; 42(12): 1807–16. doi: 10.1016/j.ejca.2006.02.022.

2. Mishra M.V., Andrews D.W., Glass J., Evans J.J., Dicker A.P., Shen X., Lawrence Y.R. Characterization and outcomes of optic nerve gliomas: a population-based analysis. J Neurooncol. 2012 May; 107(3): 591–7. doi: 10.1007/s11060-011-0783-2.

3. Brauner R., Trivin C., Zerah M., Souberbielle J.C., Doz F., Kalifa C., Sainte-Rose C. Diencephalic syndrome due to hypothalamic tumor: a model of the relationship between weight and puberty onset. J Clin Endocrinol Metab. 2006 Jul; 91(7): 2467–73. doi: 10.1210/jc.2006-0322.

4. Marec-Berard P., Szathmari A., Conter C., Mottolese C., Berlier P., Frappaz D. Improvement of diencephalic syndrome after partial surgery of optic chiasm glioma. Pediatr Blood Cancer. 2009; 53(3): 502–4. doi: 10.1002/pbc.22085.

5. Kilday J.P., Bartels U., Huang A., Barron M., Shago M., Mistry M., Zhukova N., Laperriere N., Dirks P., Hawkins C., Bouffet E, Tabori U. Favorable survival and metabolic outcome for children with diencephalic syndrome using a radiation-sparing approach. J Neurooncol. 2014 Jan; 116(1): 195–204. doi: 10.1007/s11060-013-1284-2.

6. Villares J.M., Carrión F., Gallego F.M.E., Muñoz G.A., LópezManzanares J., Alfageme R.M. Diencephalic syndrome: An uncommon cause of malnutrition. An Esp Pediatr. 2002 May; 56(5): 466–71.

7. Stival A., Lucchesi M., Farina S., Buccoliero A.M., Castiglione F., Genitori L., de Martino M., Sardi I. An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma. BMC Cancer. 2015; 15: 616. doi: 10.1186/s12885-015-1626-x.

8. Klochkova I.S., Astaf’eva L.I., Konovalov A.N., Kadashev B.A., Kalinin P.L., Sharipov O.I., Kutin M.A., Sidneva Yu.G., Shishkina L.V., Pronin I.N. A rare case of diencephalic cachexia in an adult female with craniopharyngioma (clinical case and literature (rewiew). Burdenko’s Journal of Neurosurgery. 2017; 81(5): 84–95. (in Russian). doi: 10.17116/neiro201781584-9.

9. Fleischman A., Brue C., Poussaint T.Y., Kieran M., Pomeroy S.L., Goumnerova L., Scott R.M., Cohen L.E. Diencephalic syndrome: a cause of failure to thrive and a model of partial growth hormone resistance. Pediatrics. 2005 Jun; 115(6): e742–8. doi: 10.1542/peds.2004-2237.

10. Gropman A.L., Packer R.J., Nicholson H.S., Vezina L.G., Jakacki R., Geyer R., Olson J.M., Phillips P., Needle M., Broxson E.H. Jr., Reaman G., Finlay J. Treatment of diencephalic syndrome with chemotherapy: Growth, tumor response, and long term control. Cancer. 1998 Jul 1; 83(1): 166–72. doi: 10.1002/(SICI)1097-0142(19980701)83:1<166::AIDCNCR22>3.0.CO;2-U

11. Scalzone M., Coccia P., Ruggiero A., Lazzareschi I., Mastrangelo S., Riccardi R. Diencephalic syndrome and brain tumours: A rare cause of growth failure. Eur J Oncol 2009; 14(1): 53–56.

12. Cavicchiolo M.E., Opocher E., Daverio M., Bendini M., Viscardi E., Bisogno G., Perilongo G., Da Dalt L. Diencephalic syndrome as sign of tumor progression in a child with neurofibromatosis type 1 and optic pathway glioma: a case report. Childs Nerv Syst. 2013 Oct; 29(10): 1941–5. doi: 10.1007/s00381-013-2109-5.

13. Gnekow A.K., Walker D.A., Kandels D., Picton S., Giorgio Perilongo, Grill J., Stokland T., Sandstrom P.E., Warmuth-Metz M., Pietsch T., Giangaspero F., Schmidt R., Faldum A., Kilmartin D., De Paoli A., De Salvo G.L.; of the Low Grade Glioma Consortium and the participating centers. A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma A final report. Eur J Cancer. 2017 Aug; 81: 206–225. doi: 10.1016/j.ejca.2017.04.019. Epub 2017 Jun 22.

14. Russell A.A. A diencephalic syndrome of emaciation in infancy and childhood. Arch Dis Child 1951; 26: 274.

15. Gnekow A.K., Falkenstein F., von Hornstein S., Zwiener I., Berkefeld S., Bison B., Warmuth-Metz M., Driever P.H., Soerensen N., Kortmann R.D., Pietsch T., Faldum A. Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low- grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology. Neuro Oncol. 2012 Oct; 14(10): 1265–84. doi: 10.1093/neuonc/nos202.

16. Pillai M.G., Unnikrishnan A.G., Nair V., Jayakumar R.V., Kumar H. Diencephalic cachexia: a rare cause for failure to thrive. J Pediatr. 2005 Nov; 147(5): 713. doi: 10.1016/j.jpeds.2005.04.024.

17. Perilongo G., Carollo C., Salviati L., Murgia A., Pillon M., Basso G., Gardiman M., Laverda A. Diencephalic syndrome and disseminated juvenile pilocytic astrocytomas of the hypothalamic-optic chiasm region. Cancer. 1997 Jul 1; 80(1): 142–6. doi: 10.1002/(sici)1097-0142(19970701)80:1<142::aid-cncr19>3.0.co;2-y.

18. Johnson M.W., Eberhart C.G., Perry A., Tihan T., Cohen K.J., Rosenblum M.K., Rais-Bahrami S., Goldthwaite P., Burger P.C. Spectrum of pilomyxoid astrocytomas: intermediate pilomyxoid tumors. Am J Surg Pathol. 2010 Dec; 34(12): 1783–91. doi: 10.1097/PAS.0b013e3181fd66c3.

19. Mahore A., Kammar A., Dange N., Epari S., Goel A. Diencephalic juvenile pilomyxoid astrocytoma with leptomeningeal dissemination. Turk Neurosurg. 2011; 21(2): 222–5. doi: 10.5137/1019-5149.JTN.2638-09.1.

20. Rakotonjanahary J., De Carli E., Delion M., Kalifa C., Grill J., Doz F., Leblond P., Bertozzi A.I., Rialland X.; Brain Tumor Committee of SFCE. Mortality in Children with Optic Pathway Glioma Treated with UpFront BB-SFOP Chemotherapy. PLoS One. 2015 Jun 22; 10(6): e0127676. doi: 10.1371/journal.pone.0127676.

21. Valiakhmetova E.F.,Budanov O.I., Gorelyshev S.K., Serova N.K., Lasareva L.A., Shiskina L.V., Mazerkina N.A., Trunin Y.Y., Chulkova S.V., Grishchenko N.V., Egorova A.V., Papusha L.I., Novichkova G.A., Karachunskii A.I. Optic pathway gliomas in children: prognostic factors, response assessment, role of carboplatin and vincristine chemotherapy regime. Pediatric Hematology/Oncology and Immunopathology. 2019; 18(1): 62–72. (in Russian). doi: 10.24287/1726-1708-2019-18-1-62-72.

22. Singh D.K., Behari S., Jaiswal A.K., Sahu R.N., Srivastava A.K., Mehrotra A., Dabadgaon P. Pediatric anterior visual pathway gliomas: trends in fluid and electrolyte dynamics and their management nuances. Childs Nerv Syst. 2015 Mar; 31(3): 359–71. doi: 10.1007/s00381-014-2606-1.