Impact of Surgery and Adjuvant Therapy on Balance Function in Children and Adolescents with Cerebellar Tumors

Abstract

Objectives: This study examined the effects of posterior fossa tumor surgery and concomitant irradiation and/or chemotherapy on the long-term recovery of balance function in children and adolescent patients. Subjects and Methods: 22 patients, treated during childhood for a benign (n = 14) or malignant cerebellar tumor (n = 8), were examined in chronic state (mean latency between surgery and testing: 7.7 years, range 3 - 17 years). Postural impairments were assessed with static and dynamic posturography. All cerebellar lesions were documented by standardized and normalized MRI data. Healthy age- and gender-matched subjects served as a control group. Results: Comparing the balance function of (i) children with or without affected cerebellar nuclei and (ii) children with and without adjuvant chemotherapy and/or radiotherapy revealed that damage to the cerebellar nuclei had more impact on neurological impairment than concomitant tumor therapy. Balance abnormalities were most pronounced when a lesion affected the fastigial nucleus. Chemotherapy with its neurological side effect was associated with enhanced postural sway in only two children with malignant tumors. Conclusions: The study results indicate that the sparing of the deep cerebellar nuclei had the greatest impact on the recovery of balance function in pediatric patients treated for both a benign or malignant cerebellar tumor.

Key words

Ataxia - cerebellum - brain tumor - chemotherapy - balance control

References

• 1 Albright A L, Wisoff J H, Zeltzer P M, Boyett J M, Rorke L B, Stanley P. Effects of medulloblastoma resections on outcome in children: A report from the children's cancer group.  Neurosurgery. 1996;  38 265-271
• 2 Bertolini P, Lassalle M, Mercier G, Raquin M A, Izzi G, Corradini N. et al . Platinum compound-related ototoxicity in children: Long-term follow-up reveals continuous worsening of hearing loss.  J Pediatr Hematol Oncol. 2004;  26 649-655
• 3 Botterell E, Fulton J. Functional localization in the cerebellum of primates. II: Lesions of the midline structures and deep cerebellar nuclei.  J Com Neurol. 1938;  69 47-62
• 4 Brett M, Leff A P, Rorden C, Ashburner J. Spatial normalization of brain images with focal lesions using cost function masking.  Neuroimage. 2001;  14 486-500
• 5 Chambers W, Sprague J M. Functional localization in the cerebellum, part ii. Somatotopic organization in cortex and nuclei.  Archives Neurol and Psychiatr. 1955;  75 653-680
• 6 Dennis M, Hetherington C, Spiegler B, Barnes M. Functional consequences of congenital cerebellar dysmorphologies and aquired cerebellar lesions of childhood. Broman S, Fletcher J The changing nervous system: Neurobehavioral consequences of early brain disorders. Oxford; Oxford University Press 1999: 172-198
• 7 Dichgans J, Diener H C. Clinical evidence for functional compartmentalization of the cerebellum. Bloedel JR, Dichgans J, Precht W Cerebellar Functions. Berlin, Heidelberg; Springer-Verlag 1984: 126-147
• 8 Dimitrova A, Weber J, Redies C, Kindsvater K, Maschke M, Kolb F P. et al . MRI atlas of the human cerebellar nuclei.  Neuroimage. 2002;  17 240-255
• 9 Duman O, Tezcan G, Hazar V. Treatment of vincristine-induced cranial polyneuropathy.  J Pediatr Hematol Oncol. 2005;  27 241-242
• 10 Eckmiller R, Westheimer G. Compensation of oculomotor deficits in monkeys with neonatal cerebellar ablations.  Exp Brain Res. 1983;  49 315-326
• 11 Glickstein M. The cerebellum and motor learning.  Curr Opin Neurobiol. 1992;  2 802-806
• 12 Grill J, Viguier D, Kieffer V, Bulteau C, Sainte-Rose C, Hartmann O. et al . Critical risk factors for intellectual impairment in children with posterior fossa tumors: The role of cerebellar damage.  J Neurosurg. 2004;  101 152-158
• 13 Grodd W, Hulsmann E, Lotze M, Wildgruber D, Erb M. Sensorimotor mapping of the human cerebellum: FMRI evidence of somatotopic organization.  Hum Brain Mapp. 2001;  13 55-73
• 14 Kaatsch P, Rickert C H, Kuhl J, Schuz J, Michaelis J. Population-based epidemiologic data on brain tumors in german children.  Cancer. 2001;  92 3155-3164
• 15 Kitsigianis G A, O'Leary D P, Davis L L. Active head-movement analysis of cisplatin-induced vestibulotoxicity.  Otolaryngol Head Neck Surg. 1988;  98 82-87
• 16 Konczak J, Schoch B, Dimitrova A, Gizewski E, Timmann D. Functional recovery of children and adolescents after cerebellar tumor resection.  Brain. 2005;  128 1428-1441
• 17 Kortmann R D, Kuhl J, Timmermann B, Mittler U, Urban C, Budach V. et al . Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: Results of the German prospective randomized trial hit '91.  Int J Radiat Oncol Biol Phys. 2000;  46 269-279
• 18 Kuehl J, Berthold F, Bode U, Bucsky P, Graf N, Gnekow A. et al . Preradiation chemotherapy of children with poor-prognosis medulloblastoma.  Am J Pediatr Hematol Oncol. 1993;  15 Suppl A 67-71
• 32 Luft A R, Skalej M, Welte D, Kolb R, Burk K, Schulz J B. et al . A new semiautomated, three-dimensional technique allowing precise quantification of total and regional cerebellar volume using MRI.  Magn Reson Med. 1998;  40 143-151
• 19 Muller L, Kramm C M, Tenenbaum T, Wessalowski R, Gobel U. Treatment of vincristine-induced bilateral ptosis with pyridoxine and pyridostigmine.  Pediatr Blood Cancer. 2004;  42 287-288
• 20 Packer R J. Brain tumors in children.  Arch Neurol. 1999;  56 421-425
• 21 Pollack I F. Brain tumors in children.  N Engl J Med. 1994;  331 1500-1507
• 22 Quasthoff S, Hartung H P. Chemotherapy-induced peripheral neuropathy.  J Neurol. 2002;  249 9-17
• 23 Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N. et al . Treatment of early childhood medulloblastoma by postoperative chemotherapy alone.  N Engl J Med. 2005;  352 978-986
• 24 Schmahmann J D, Dojon J, Toga A W, Petrides M, Evans A C. MRI atlas of the human cerebellum. San Diego; Academic Press 2000
• 25 Schoch B, Dimitrova A, Gizewski E R, Timmann D. Functional localization in the human cerebellum based on voxelwise statistical analysis: A study of 90 patients.  Neuroimage. 2006;  30 36-51
• 26 Thach W T, Bastian A J. Role of the cerebellum in the control and adaptation of gait in health and disease.  Prog Brain Res. 2004;  143 353-366
• 27 Thach W T, Kane S A, Mink J W, Goodkin H P. Cerebellar output: Multiple maps and models of control in movement coordination. Llinas RS, Stelo C The Cerebellum Revisited. New York; Springer Verlag 1992: 283-300
• 28 Timmermann B, Kortmann R D, Kuhl J, Meisner C, Dieckmann K, Pietsch T. et al . Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: Results of the prospective german brain tumor trials hit 88/89 and 91.  J Clin Oncol. 2002;  20 842-849
• 29 Trotti A, Colevas A D, Setser A, Rusch V, Jaques D, Budach V. et al . CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment.  Semin Radiat Oncol. 2003;  13 176-181
• 30 Trouillas P, Takayanagi T, Hallett M, Currier R D, Subramony S H, Wessel K. et al . 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. 1997;  145 205-211
• 31 Verstappen C C, Koeppen S, Heimans J J, Huijgens P C, Scheulen M E, Strumberg D. et al . Dose-related vincristine-induced peripheral neuropathy with unexpected off-therapy worsening.  Neurology. 2005;  64 1076-1077