Journal of Neuro-Oncology

, Volume 116, Issue 1, pp 195–204 | Cite as

Favorable survival and metabolic outcome for children with diencephalic syndrome using a radiation-sparing approach

  • John-Paul Kilday
  • Ute Bartels
  • Annie Huang
  • Mary Barron
  • Mary Shago
  • Matthew Mistry
  • Nataliya Zhukova
  • Normand Laperriere
  • Peter Dirks
  • Cynthia Hawkins
  • Eric Bouffet
  • Uri TaboriEmail author
Clinical Study


Diencephalic syndrome (DS) is a clinical disorder of metabolism associated with poor outcome in children with low-grade gliomas (LGGs). Since survival has been primarily reported with aggressive therapy, we report outcome data for these patients using a current, contrasting chemotherapy-driven approach. We performed a population-based review of DS patients treated with chemotherapy from 1997–2012. Metabolic rate was assessed in selected cases using open-circuit calorimetry to generate resting energy expenditure (REE) data. Tumor tissue was analyzed for BRAF alterations. Survival was compared with an age-related, radiotherapy naïve cohort of non-DS children with location-matched LGGs. Nine children (1.7 % of 520 LGG diagnoses) fulfilled DS criteria. The median diagnostic age was 1.49 years (0.55–2.69 years), although neurofibromatosis Type-I patients were older (p = 0.005). All tumors analyzed exhibited either NF1 mutation or BRAF fusion. Seven tumors were histologically confirmed as low grade astrocytomas, one demonstrated neurocytic features, and one NF1 case was diagnosed using imaging and clinical criteria. All patients received chemotherapy, with seven cases also receiving initial nutritional supplementation. All nine gained weight after only 6 months of treatment. Two DS patients had serial REE measurements, revealing a hypermetabolic state (over 200 % of predicted REE) at diagnosis which reduced to normal range with therapy. First-line chemotherapy treatment resulted in one minor response, stable disease in four cases, with progression in the remaining four patients. Although DS patients demonstrated inferior initial progression-free survival when compared to non-DS counterparts (5 years: 22 versus 60 %, p = 0.015), all DS children remain alive at a median follow up of 5.3 years (1.2–14.9 years) with none requiring radiotherapy. Long-term sequelae included pituitary and visual dysfunction, learning difficulties and paradoxical, inappropriate weight gain. DS can be managed with non-aggressive chemotherapeutic, radiation-sparing strategies supplemented by temporary nutritional support. Multiple lines of therapy may be required to overcome disease progression but excellent survival and metabolic outcomes can be achieved. Continued surveillance is mandatory to prevent significant weight gain and support affected children with clinical sequelae.


Diencephalic syndrome Pediatric Low grade glioma Chemotherapy Radiation 



Supported by B.R.A.I.N. child, Canada (; Charity 10808 4419 RR 0001.

Conflict of interest

All authors declare no conflict of interest.

Supplementary material

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Supplementary material 1 (PDF 14 kb)
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Supplementary material 2 (PDF 101 kb)
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Supplementary material 3 (PDF 68 kb)
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Supplementary material 4 (PDF 90 kb)


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • John-Paul Kilday
    • 1
  • Ute Bartels
    • 1
  • Annie Huang
    • 1
  • Mary Barron
    • 2
  • Mary Shago
    • 3
  • Matthew Mistry
    • 3
  • Nataliya Zhukova
    • 1
  • Normand Laperriere
    • 6
  • Peter Dirks
    • 4
  • Cynthia Hawkins
    • 5
  • Eric Bouffet
    • 1
  • Uri Tabori
    • 1
    Email author
  1. 1.Division of Haematology/Oncology, Department of Pediatric Neuro-OncologyHospital for Sick Children, University Avenue, University of TorontoTorontoCanada
  2. 2.Division of Clinical DieteticsHospital for Sick ChildrenTorontoCanada
  3. 3.Division of Molecular Genetics (Cytogenetics)Hospital for Sick ChildrenTorontoCanada
  4. 4.Division of NeurosurgeryHospital for Sick ChildrenTorontoCanada
  5. 5.Division of PathologyHospital for Sick ChildrenTorontoCanada
  6. 6.Department of Radiation OncologyPrincess Margaret HospitalTorontoCanada

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