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DTI fiber tractography of cerebro-cerebellar pathways and clinical evaluation of ataxia in childhood posterior fossa tumor survivors

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Abstract

Pediatric posterior fossa (PF) tumor survivors experience long-term motor deficits. Specific cerebrocerebellar connections may be involved in incidence and severity of motor dysfunction. We examined the relationship between long-term ataxia as well as fine motor function and alteration of differential cerebellar efferent and afferent pathways using diffusion tensor imaging (DTI) and tractography. DTI-based tractography was performed in 19 patients (10 pilocytic astrocytoma (PA) and 9 medulloblastoma patients (MB)) and 20 healthy peers. Efferent Cerebello-Thalamo-Cerebral (CTC) and afferent Cerebro-Ponto-Cerebellar (CPC) tracts were reconstructed and analyzed concerning fractional anisotropy (FA) and volumetric measurements. Clinical outcome was assessed with the International Cooperative Ataxia Rating Scale (ICARS). Kinematic parameters of fine motor function (speed, automation, variability, and pressure) were obtained by employing a digitizing graphic tablet. ICARS scores were significantly higher in MB patients than in PA patients. Poorer ICARS scores and impaired fine motor function correlated significantly with volume loss of CTC pathway in MB patients, but not in PA patients. Patients with pediatric post-operative cerebellar mutism syndrome showed higher loss of CTC pathway volume and were more atactic. CPC pathway volume was significantly reduced in PA patients, but not in MB patients. Neither relationship was observed between the CPC pathway and ICARS or fine motor function. There was no group difference of FA values between the patients and healthy peers. Reduced CTC pathway volumes in our cohorts were associated with severity of long-term ataxia and impaired fine motor function in survivors of MBs. We suggest that the CTC pathway seems to play a role in extent of ataxia and fine motor dysfunction after childhood cerebellar tumor treatment. DTI may be a useful tool to identify relevant structures of the CTC pathway and possibly avoid surgically induced long-term neurological sequelae.

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References

  1. Pollack IF (1994) Brain tumors in children. N Engl J Med 331(22):1500–1507

    Article  CAS  PubMed  Google Scholar 

  2. Piscione PJ et al (2014) Physical functioning in pediatric survivors of childhood posterior fossa brain tumors. Neuro-oncology 16(1):147–155

    Article  PubMed  Google Scholar 

  3. Pollack IF (2012) Ataxia resulting from posterior fossa tumors of childhood and other mass lesions. Handb Clin Neurol 103:161–173

    Article  PubMed  Google Scholar 

  4. Rueckriegel SM et al (2009) Loss of fine motor function correlates with ataxia and decline of cognition in cerebellar tumor survivors. Pediatr Blood Cancer 53(3):424–431

    Article  PubMed  Google Scholar 

  5. Aarsen FK et al (2004) Long-term sequelae in children after cerebellar astrocytoma surgery. Neurology 62(8):1311–1316

    Article  CAS  PubMed  Google Scholar 

  6. LeBaron S et al (1988) Assessment of quality of survival in children with medulloblastoma and cerebellar astrocytoma. Cancer 62(6):1215–1222

    Article  CAS  PubMed  Google Scholar 

  7. Robertson PL et al (2006) Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children’s Oncology Group. J Neurosurg 105(6 Suppl):444–451

    PubMed  Google Scholar 

  8. Wells EM et al (2010) Postoperative cerebellar mutism syndrome following treatment of medulloblastoma: neuroradiographic features and origin. J Neurosurg Pediatr 5(4):329–334

    Article  PubMed  Google Scholar 

  9. Koustenis E et al (2016) Executive function deficits in pediatric cerebellar tumor survivors. Eur J Paediatr Neurol 20(1):25–37

    Article  PubMed  Google Scholar 

  10. Rueckriegel SM et al (2015) Cerebral white matter fractional anisotropy and tract volume as measured by MR imaging are associated with impaired cognitive and motor function in pediatric posterior fossa tumor survivors. Pediatr Blood Cancer 62(7):1252–1258

    Article  PubMed  Google Scholar 

  11. Siffert J et al (2000) Neurological dysfunction associated with postoperative cerebellar mutism. J Neurooncol 48(1):75–81

    Article  CAS  PubMed  Google Scholar 

  12. Ozgur BM et al (2006) The pathophysiologic mechanism of cerebellar mutism. Surg Neurol 66(1):18–25

    Article  PubMed  Google Scholar 

  13. Friedland J (1990) Development and breakdown of written language. J Commun Disord 23(3):171–186

    Article  CAS  PubMed  Google Scholar 

  14. McHale K, Cermak SA (1992) Fine motor activities in elementary school: preliminary findings and provisional implications for children with fine motor problems. Am J Occup Ther 46(10):898–903

    Article  CAS  PubMed  Google Scholar 

  15. Konczak J et al (2005) Functional recovery of children and adolescents after cerebellar tumour resection. Brain 128(Pt 6):1428–1441

    Article  PubMed  Google Scholar 

  16. Khajuria RK et al (2015) Morphological brain lesions of pediatric cerebellar tumor survivors correlate with inferior neurocognitive function but do not affect health-related quality of life. Childs Nerv Syst 31(4):569–580

    Article  PubMed  Google Scholar 

  17. Kuper M et al (2013) Location and restoration of function after cerebellar tumor removal-a longitudinal study of children and adolescents. Cerebellum 12(1):48–58

    Article  CAS  PubMed  Google Scholar 

  18. Puget S et al (2009) Injuries to inferior vermis and dentate nuclei predict poor neurological and neuropsychological outcome in children with malignant posterior fossa tumors. Cancer 115(6):1338–1347

    Article  PubMed  Google Scholar 

  19. Schoch B et al (2010) Balance control in sitting and standing in children and young adults with benign cerebellar tumors. Cerebellum 9(3):324–335

    Article  PubMed  Google Scholar 

  20. Kusano Y et al (2006) Transient cerebellar mutism caused by bilateral damage to the dentate nuclei after the second posterior fossa surgery. Case report. J Neurosurg 104(2):329–331

    Article  PubMed  Google Scholar 

  21. Miller NG et al (2010) Cerebellocerebral diaschisis is the likely mechanism of postsurgical posterior fossa syndrome in pediatric patients with midline cerebellar tumors. AJNR Am J Neuroradiol 31(2):288–294

    Article  CAS  PubMed  Google Scholar 

  22. Morris EB et al (2009) Proximal dentatothalamocortical tract involvement in posterior fossa syndrome. Brain 132(Pt 11):3087–3095

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rueckriegel SM et al (2010) Differences in supratentorial damage of white matter in pediatric survivors of posterior fossa tumors with and without adjuvant treatment as detected by magnetic resonance diffusion tensor imaging. Int J Radiat Oncol Biol Phys 76(3):859–866

    Article  PubMed  Google Scholar 

  24. Rueckriegel SM, Driever PH, Bruhn H (2012) Supratentorial neurometabolic alterations in pediatric survivors of posterior fossa tumors. Int J Radiat Oncol Biol Phys 82(3):1135–1141

    Article  PubMed  Google Scholar 

  25. Soelva V et al (2013) Fronto-cerebellar fiber tractography in pediatric patients following posterior fossa tumor surgery. Childs Nerv Syst 29(4):597–607

    Article  PubMed  Google Scholar 

  26. Avula S et al (2015) Diffusion abnormalities on intraoperative magnetic resonance imaging as an early predictor for the risk of posterior fossa syndrome. Neuro-oncology 17(4):614–622

    Article  PubMed  Google Scholar 

  27. Baillieux H et al (2007) Posterior fossa syndrome after a vermian stroke: a new case and review of the literature. Pediatr Neurosurg 43(5):386–395

    Article  PubMed  Google Scholar 

  28. Huber JF et al (2007) Long-term neuromotor speech deficits in survivors of childhood posterior fossa tumors: effects of tumor type, radiation, age at diagnosis, and survival years. J Child Neurol 22(7):848–854

    Article  PubMed  Google Scholar 

  29. Law N et al (2011) Cerebello-thalamo-cerebral connections in pediatric brain tumor patients: impact on working memory. Neuroimage 56(4):2238–2248

    Article  PubMed  Google Scholar 

  30. Law N et al (2012) Clinical and neuroanatomical predictors of cerebellar mutism syndrome. Neuro-oncology 14(10):1294–1303

    Article  PubMed  PubMed Central  Google Scholar 

  31. Marien P et al (2001) The lateralized linguistic cerebellum: a review and a new hypothesis. Brain Lang 79(3):580–600

    Article  CAS  PubMed  Google Scholar 

  32. Patay Z et al (2014) Quantitative longitudinal evaluation of diaschisis-related cerebellar perfusion and diffusion parameters in patients with supratentorial hemispheric high-grade gliomas after surgery. Cerebellum 13(5):580–587

    Article  PubMed  Google Scholar 

  33. Schmahmann JD, Shermann JC (1998) The cerebellar cognitive affective syndrome. Brain 121(Pt 4):561–579

    Article  PubMed  Google Scholar 

  34. Schmahmann JD, Pandya DN (2008) Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems. Cortex 44(8):1037–1066

    Article  PubMed  PubMed Central  Google Scholar 

  35. Jissendi P, Baudry S, Baleriaux D (2008) Diffusion tensor imaging (DTI) and tractography of the cerebellar projections to prefrontal and posterior parietal cortices: a study at 3 T. J Neuroradiol 35(1):42–50

    Article  CAS  PubMed  Google Scholar 

  36. Kamali A et al (2010) Diffusion tensor tractography of the human brain cortico-ponto-cerebellar pathways: a quantitative preliminary study. J Magn Reson Imaging 32(4):809–817

    Article  PubMed  PubMed Central  Google Scholar 

  37. Salamon N et al (2007) White matter fiber tractography and color mapping of the normal human cerebellum with diffusion tensor imaging. J Neuroradiol 34(2):115–128

    Article  CAS  PubMed  Google Scholar 

  38. Salmi J et al (2010) Cognitive and motor loops of the human cerebro-cerebellar system. J Cogn Neurosci 22(11):2663–2676

    Article  PubMed  Google Scholar 

  39. Law N et al (2015) Visualization and segmentation of reciprocal cerebrocerebellar pathways in the healthy and injured brain. Human Brain Mapp 36(7):2615–2628

    Article  Google Scholar 

  40. Trouillas P et al (1997) International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci 145(2):205–211

    Article  CAS  PubMed  Google Scholar 

  41. Schoch B et al (2007) Reliability and validity of ICARS in focal cerebellar lesions. Mov Disord 22(15):2162–2169

    Article  PubMed  Google Scholar 

  42. Brandsma R et al (2014) Ataxia rating scales are age-dependent in healthy children. Dev Med Child Neurol 56(6):556–563

    Article  PubMed  Google Scholar 

  43. Rueckriegel SM et al (2008) Influence of age and movement complexity on kinematic hand movement parameters in childhood and adolescence. Int J Dev Neurosci 26(7):655–663

    Article  PubMed  Google Scholar 

  44. Wakana S et al (2004) Fiber tract-based atlas of human white matter anatomy. Radiology 230(1):77–87

    Article  PubMed  Google Scholar 

  45. Mori S, van Zijl PC (2002) Fiber tracking: principles and strategies - a technical review. NMR Biomed 15(7–8):468–480

    Article  PubMed  Google Scholar 

  46. Unrath A et al (2008) Directional colour encoding of the human thalamus by diffusion tensor imaging. Neurosci Lett 434(3):322–327

    Article  CAS  PubMed  Google Scholar 

  47. Wiegell MR et al (2003) Automatic segmentation of thalamic nuclei from diffusion tensor magnetic resonance imaging. Neuroimage 19(2 Pt 1):391–401

    Article  PubMed  Google Scholar 

  48. Huber JF et al (2006) Long-term effects of transient cerebellar mutism after cerebellar astrocytoma or medulloblastoma tumor resection in childhood. Childs Nerv Syst 22(2):132–138

    Article  PubMed  Google Scholar 

  49. Pollack IF et al (1995) Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology. Neurosurgery 37(5):885–893

    Article  CAS  PubMed  Google Scholar 

  50. Steinbok P et al (2003) Mutism after posterior fossa tumour resection in children: incomplete recovery on long-term follow-up. Pediatr Neurosurg 39(4):179–183

    Article  PubMed  Google Scholar 

  51. Steinlin M et al (2003) Neuropsychological long-term sequelae after posterior fossa tumour resection during childhood. Brain 126(Pt 9):1998–2008

    Article  PubMed  Google Scholar 

  52. Wells EM et al (2008) The cerebellar mutism syndrome and its relation to cerebellar cognitive function and the cerebellar cognitive affective disorder. Dev Disabil Res Rev 14(3):221–228

    Article  PubMed  Google Scholar 

  53. Crutchfield JS et al (1994) Postoperative mutism in neurosurgery. Report of two cases. J Neurosurg 81(1):115–121

    Article  CAS  PubMed  Google Scholar 

  54. Frim DM, Ogilvy CS (1995) Mutism and cerebellar dysarthria after brain stem surgery: case report. Neurosurgery 36(4):854–857

    Article  CAS  PubMed  Google Scholar 

  55. Hirsch JF et al (1979) Medulloblastoma in childhood. Survival and functional results. Acta Neurochir (Wien) 48(1–2):1–15

    Article  CAS  Google Scholar 

  56. Levisohn L, Cronin-Golomb A, Schmahmann JD (2000) Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population. Brain 123(Pt 5):1041–1050

    Article  PubMed  Google Scholar 

  57. Cochrane DD et al (1994) The surgical and natural morbidity of aggressive resection for posterior fossa tumors in childhood. Pediatr Neurosurg 20(1):19–29

    Article  CAS  PubMed  Google Scholar 

  58. Perreault S et al (2014) Time-dependent structural changes of the dentatothalamic pathway in children treated for posterior fossa tumor. AJNR Am J Neuroradiol 35(4):803–807

    Article  CAS  PubMed  Google Scholar 

  59. Schoch B et al (2006) Impact of surgery and adjuvant therapy on balance function in children and adolescents with cerebellar tumors. Neuropediatrics 37(6):350–358

    Article  CAS  PubMed  Google Scholar 

  60. Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system - a technical review. NMR Biomed 15(7–8):435–455

    Article  PubMed  Google Scholar 

  61. Barnea-Goraly N et al (2005) White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study. Cereb Cortex 15(12):1848–1854

    Article  PubMed  Google Scholar 

  62. Paus T (2005) Mapping brain maturation and cognitive development during adolescence. Trends Cogn Sci 9(2):60–68

    Article  PubMed  Google Scholar 

  63. Suzuki Y et al (2003) Absolute eigenvalue diffusion tensor analysis for human brain maturation. NMR Biomed 16(5):257–260

    Article  PubMed  Google Scholar 

  64. Wakamoto H et al (2006) Diffusion tensor imaging of the corticospinal tract following cerebral hemispherectomy. J Child Neurol 21(7):566–571

    Article  PubMed  Google Scholar 

  65. Stieltjes B et al (2001) Diffusion tensor imaging and axonal tracking in the human brainstem. Neuroimage 14(3):723–735

    Article  CAS  PubMed  Google Scholar 

  66. Alexander AL et al (2007) Diffusion tensor imaging of the brain. Neurother 4(3):316–329

    Article  Google Scholar 

  67. Ward E et al (2014) Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64(2):83–103

    Article  PubMed  Google Scholar 

  68. Jemal A et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58(2):71–96

    Article  PubMed  Google Scholar 

  69. Chen X et al (2007) Diffusion tensor imaging and white matter tractography in patients with brainstem lesions. Acta Neurochir (Wien) 149(11):1117-1131. (Discussion 1131)

    Article  Google Scholar 

  70. Laundre BJ et al (2005) Diffusion tensor imaging of the corticospinal tract before and after mass resection as correlated with clinical motor findings: preliminary data. AJNR Am J Neuroradiol 26(4):791–796

    PubMed  Google Scholar 

  71. Lazar M et al (2006) White matter reorganization after surgical resection of brain tumors and vascular malformations. AJNR Am J Neuroradiol 27(6):1258–1271

    CAS  PubMed  Google Scholar 

  72. Ulmer JL et al (2004) The role of diffusion tensor imaging in establishing the proximity of tumor borders to functional brain systems: implications for preoperative risk assessments and postoperative outcomes. Technol Cancer Res Treat 3(6):567–576

    Article  PubMed  Google Scholar 

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Acknowledgments

We gratefully thank “KINDerLEBEN e.V.” for supporting E. Koustenis and the “Kind-Philipp-Foundation” for supporting SM Rueckriegel.

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    Authors and Affiliations

    1. Pediatric Neurosurgery, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

      Myung Eun Oh & Ulrich-Wilhelm Thomale

    2. Pediatric Neurooncology Program, Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany

      Pablo Hernáiz Driever, Rajiv K. Khajuria, Stefan Mark Rueckriegel & Elisabeth Koustenis

    3. Department of Neurosurgery, University Hospital Würzburg, Würzburg, Germany

      Stefan Mark Rueckriegel

    4. Institute of Diagnostic and Interventional Radiology, Friedrich Schiller University Jena, Jena, Germany

      Harald Bruhn

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    1. Myung Eun Oh
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    Myung Eun Oh and Pablo Hernáiz Driever have contributed equally to this study

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    Oh, M.E., Driever, P.H., Khajuria, R.K. et al. DTI fiber tractography of cerebro-cerebellar pathways and clinical evaluation of ataxia in childhood posterior fossa tumor survivors. J Neurooncol 131, 267–276 (2017). https://doi.org/10.1007/s11060-016-2290-y

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