@article{LieberBlankenburgApeletal.2018,
  author    = {S. Lieber and Markus R. Blankenburg and K. Apel and Gerrit Hirschfeld and Pablo Hern{\´a}iz Driever and T. Reindl},
  title     = {Small-fiber neuropathy and pain sensitization in survivors of pediatric acute lymphoblastic leukemia},
  series   = {European Journal of Paediatric Neurology},
  volume    = {22},
  number    = {3},
  issn      = {1532-2130},
  doi       = {10.1016/j.ejpn.2017.12.019},
  pages     = {457 -- 469},
  year      = {2018},
  abstract  = {Background: Chemotherapy-induced Peripheral Neuropathy (CIPN) of large-fibers affects up to 20\% of survivors of pediatric acute lymphoblastic leukemia (ALL). We aimed to describe small-fiber toxicity and pain sensitization in this group. Methods: In a cross-sectional, bicentric study we assessed 46 survivors of pediatric ALL (Mean age: 5.7 ± 3.5 years at diagnosis, median 2.5 years after therapy; males: 28). Inclusion criteria: ≥6 years of age, ≥3 months after last administration of Vincristine, and cumulative dose of Vincristine 12 mg/m2. We used a reduced version of the Pediatric-modified Total Neuropathy Score (Ped-mTNS) as bedside test and Quantitative Sensory Testing (QST) for assessment of small- and large-fiber neuropathy as well as pain sensitization. We employed Nerve Conduction Studies (NCS) as the most accurate tool for detecting large-fiber neuropathy. Results: Fifteen survivors (33\%) had abnormal rPed-mTNS values (≥4 points) and 5 survivors (11\%) reported pain. In QST, the survivor group showed significant (p < 0.001) inferior large-fiber function and pain sensitization when compared to healthy matched peers. We identified deficits of vibration in 33 (72\%) and tactile hypoesthesia in 29 (63\%), hyperalgesia to blunt pressure in 19 (41\%), increased mechanical pain sensitivity in 12 (26\%) and allodynia in 16 (35\%) of 46 survivors. Only 7 survivors (15\%) had pathologic NCS. Conclusion: QST is a sensitive tool that revealed signs of large-fiber neuropathy in two thirds, small-fiber neuropathy and pain sensitization in one third of survivors. Prospective studies using QST in pediatric oncology may help to elucidate the pathophysiology of small-fiber neuropathy and pain sensitization as well as their relevance for quality of survival.},
  language  = {en}
}