Children with acute leukemia (ALL) often suffer from several disease and treatment related side-effects during treatment. The aim of the present study was to determine the gross and fine motor functioning and basic cognitive performance of children (n = 25) with ALL who were undergoing induction or consolidation chemotherapy and to compare these characteristics to a normative group (n = 21) of age-matched typically developing children. We assessed the children’s motor functions with the Bruininks-Oseretsky Test of Motor Proficiency Second Edition-Short Form and the Nine-hole Peg Test, and we used the Modified Mini-Mental State Exam (MMSE) to evaluate their cognitive performance. Compared to the normative group, children with ALL had lower scores on total motor proficiency and sub-tests scores of motor functions (p < .05), and on the Nine-hole Peg Test performance (p < .05); but their cognitive performance on the MMSE was not significantly different. Children with ALL would likely benefit from structured exercise and rehabilitative interventions during chemotherapy to prevent and/or ameliorate ALL-related motor dysfunction. We also suggest that their cognitive functioning should be further investigated with more extensive well-validated neurocognitive tests for children (e.g., the Wechsler intelligence scales).
ArthanatS.NochajskiS. M.StoneJ. (2004).
The international classification of functioning, disability and health and its application to cognitive disorders. Disability and Rehabilitation,
26(4), 235–245. https://doi.org/10.1080/09638280310001644889
2.
BessonP. S.LabbéE. E. (1997).
Use of the modified mini-mental state examination with children. Journal of Child Neurology,
12(7), 455–460. https://doi.org/10.1177/088307389701200708
3.
BraamK. I.van der TorreP.TakkenT.VeeningM. A.van Dulmen-den BroederE.KaspersG. J. (2016).
Physical exercise training interventions for children and young adults during and after treatment for childhood cancer. Cochrane Database of Systematic Reviews,
31(3), CD008796. https://doi.org/10.1002/14651858.CD008796.pub2
4.
BrooksB. L.ShermanE. M. S.StraussE. (2009).
NEPSY-II: A developmental neuropsychological assessment, second edition. Child Neuropsychology,
16(1), 80–101. https://doi.org/10.1080/09297040903146966
5.
BrowneK. (2005).
Snowball sampling: Using social networks to research non‐heterosexual women. International Journal of Social Research Methodology,
8(1), 47–60. https://doi.org/10.1080/1364557032000081663
6.
BruininksR. H. (2005). Bruininks-Oseretsky test of motor proficiency, (BOT-2).
Pearson Assessment.
7.
BuizerA. I.de SonnevilleL. M.van den Heuvel–EibrinkM. M.VeermanA. J. (2005).
Chemotherapy and attentional dysfunction in survivors of childhood acute lymphoblastic leukemia: Effect of treatment intensity. Pediatric Blood & Cancer,
45(3), 281–290. https://doi.org/10.1002/pbc.20397
8.
BuizerA. I.de SonnevilleL. M.VeermanA. J. (2009).
Effects of chemotherapy on neurocognitive function in children with acute lymphoblastic leukemia: A critical review of the literature. Pediatric Blood & Cancer,
52(4), 447–454. https://doi.org/10.1002/pbc.21869
9.
CampbellL. K.ScadutoM.SharpW.DuftonL.Van SlykeD.WhitlockJ. A.CompasB. (2007).
A meta‐analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia. Pediatric Blood & Cancer,
49(1), 65–73. https://doi.org/10.1002/pbc.20860
10.
CareyM. E.HockenberryM. J.MooreI. M.HutterJ. J.KrullK. R.PasvogelA.KaemingkK. L. (2007).
Brief report: Effect of intravenous methotrexate dose and infusion rate on neuropsychological function one year after diagnosis of acute lymphoblastic leukemia. Journal of Pediatric Psychology,
32(2), 189–193. https://doi.org/10.1093/jpepsy/jsj114
11.
CopelandD. R.DowellR. E.FletcherJ. M.SullivanM. P.JaffeN.CangirA.FrankelL. S.JuddB. W. (1988).
Neuropsychological test performance of pediatric cancer patients at diagnosis and one year later. Journal of Pediatric Psychology,
13(2), 183–196. https://doi.org/10.1093/jpepsy/13.2.183
12.
CohenM. J. (1997). Children's memory scale manual.
The Psychological Corporation.
13.
DeitzJ. C.KartinD.KoppK. (2007).
Review of the Bruininks-Oseretsky test of motor proficiency, (BOT-2). Physical & Occupational Therapy in Pediatrics,
27(4), 87–102. https://doi.org/10.1080/J006v27n04_06
14.
FolsteinM. F.FolsteinS. E.McHughP. R. (1975).
Mini-mental state: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research,
12(3), 189–198. https://doi.org/10.1016/0022-3956(75)90026-6
15.
FreedmanD.ManlyJ. (2015). Use of normative data and measures of performance validity and symptom validity in assessment of cognitive function. Paper commissioned by the IOM committee on psychological testing, including validity testing, for social security administration disability determinations. https://www.nap.edu/resource/21704/FreedmanManlyCommissioned-paper.pdf
16.
GreenJ. L.KnightS. J.McCarthyM.De LucaC. R. (2013).
Motor functioning during and following treatment with chemotherapy for pediatric acute lymphoblastic leukemia. Pediatric Blood & Cancer,
60(8), 1261–1266. https://doi.org/10.1002/pbc.24537
Gross-KingM.Booth-JonesM.CoulurisM. (2008).
Neurocognitive impairment in children treated for cancer: How do we measure cognitive outcomes?Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses,
25(4), 227–232. https://doi.org/10.1177/1043454208321114
19.
HartmanA.Van den BosC.StijnenT.PietersR. (2008).
Decrease in peripheral muscle strength and ankle dorsiflexion as long‐term side effects of treatment for childhood cancer. Pediatric Blood & Cancer,
50(4), 833–837. https://doi.org/10.1002/pbc.21325
20.
HowladerN.NooneA. M.KrapchoM.GarshellJ.NeymanN.AltekruseS. F.KosaryC. L.YuM.RuhlJ.TatalovichZ.ChoH.MariottoA.LewisD. R.ChenH. S.FeuerE. J.CroninK. A. (2013). SEER cancer statistics review, 1975–2010. https://seer.cancer.gov/archive/csr/1975_2010/
21.
HungerS. P.LuX.DevidasM.CamittaB. M.GaynonP. S.WinickN. J.ReamanG. H.CarrollW. L. (2012).
Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: A report from the children's oncology group. Journal of Clinical Oncology,
30(14), 1663–1669. https://doi.org/10.1200/JCO.2011.37.8018
22.
JainM.PassiG. R. (2005).
Assessment of a modified Mini-Mental scale for cognitive functions in children. Indian Pediatrics,
42(9), 907–912.
23.
JansenN.KingmaA.TellegenP.van DommelenR. I.BoumaA.VeermanA.KampsW. A. (2005).
Feasibility of neuropsychological assessment in leukaemia patients shortly after diagnosis: Directions for future prospective research. Archives of Disease in Childhood,
90(3), 301–304. https://doi.org/10.1136/adc.2004.051839
24.
KaemingkK. L.CareyM. E.MooreI. M.HerzerM.HutterJ. J. (2004).
Math weakness in survivors of acute lymphoblastic leukemia compared to healthy children. Child Neuropsychology: A Journal on Normal and Abnormal Development in Childhood and Adolescence,
10(1), 14–23. https://doi.org/10.1076/chin.10.1.14.26240
25.
KellorM.FrostJ.SilberbergN.IversenI.CummingsR. (1971).
Hand strength and dexterity. The American Journal of Occupational Therapy : Official Publication of the American Occupational Therapy Association,
25(2), 77–83.
26.
KhanR. B.HudsonM. M.LedetD. S.MorrisE. B.PuiC. H.HowardS. C.KrullK. R.HindsP. S.CromD.BrowneE.ZhuL.RaiS.SrivastavaD.NessK. K. (2014).
Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: A prospective cross-sectional study. Journal of Cancer Survivorship: Research and Practice,
8(4), 688–696. https://doi.org/10.1007/s11764-014-0375-1
27.
KhanR. B.HudsonM. M.NessK. K.LiangZ.SrivastavaD.KrullK. R. (2016).
Association of attention deficit disorder with bedside anti-saccades in survivors of childhood leukemia. Journal of Child Neurology,
31(2), 131–133. https://doi.org/10.1177/0883073815583689
LehtinenS. S.HuuskonenU. E.Harila‐SaariA. H.TolonenU.VainionpääL. K.LanningB. M. (2002).
Motor nervous system impairment persists in long‐term survivors of childhood acute lymphoblastic leukemia. Cancer,
94(9), 2466–2473. https://doi.org/10.1002/cncr.10503
30.
LeoneM.ViretP.BuiH. T.LaverdièreC.KalinovaÉ.ComtoisA. S. (2014).
Assessment of gross motor skills and phenotype profile in children 9–11 years of age in survivors of acute lymphoblastic leukemia. Pediatric Blood & Cancer,
61(1), 46–52. https://doi.org/10.1002/pbc.24731
31.
MarcheseV. G.ChiarelloL. A.LangeB. J. (2003).
Strength and functional mobility in children with acute lymphoblastic leukemia. Medical and Pediatric Oncology,
40(4), 230–232. https://doi.org/10.1002/mpo.10266
32.
MarcheseV. G.ChiarelloL. A.LangeB. J. (2004).
Effects of physical therapy intervention for children with acute lymphoblastic leukemia. Pediatric Blood & Cancer,
42(2), 127–133. https://doi.org/10.1002/pbc.10481.
33.
MargolinJ. F.PoplackD. G. (2002). Acute lymphoblastic leukemia. In PizzoP. A.PoplackD. G. (Eds.), Principles and practice of pediatric oncology (pp. 489–544).
Lippincott Williams & Wilkins.
34.
MartinK. L.BlizzardL.SrikanthV. K.WoodA.ThomsonR.SandersL. M.CallisayaM. L. (2013).
Cognitive function modifies the effect of physiological function on the risk of multiple falls a population-based study. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences,
68(9), 1091–1097. https://doi.org/10.1093/gerona/glt010.
35.
MonchiO.PetridesM.PetreV.WorsleyK.DagherA. (2001).
Wisconsin card sorting revisited: Distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience,
21(19), 7733–7741. https://doi.org/10.1523/JNEUROSCI.21-19-07733.2001
36.
Montour-ProulxI.KuehnS. M.KeeneD. L.BarrowmanN. J.HsuE.MatzingerM. A.MatzingerM. A.DunlapH.HaltonJ. M. (2005).
Cognitive changes in children treated for acute lymphoblastic leukemia with chemotherapy only according to the pediatric oncology group 9605 protocol. Journal of Child Neurology,
20(2), 129–133. https://doi.org/10.1177/08830738050200020901
37.
MooreB. D. (2005).
Neurocognitive outcomes in survivors of childhood cancer. Journal of Pediatric Psychology,
30(1), 51–63. https://doi.org/10.1093/jpepsy/jsi016
38.
MouraR.AndradeP. M. O.FontesP. L. B.FerreiraF. O.SalvadorL. D. S.CarvalhoM. R. S.HaaseV. G. (2017).
Mini-mental state exam for children (MMC) in children with hemiplegic cerebral palsy. Dementia & Neuropsychologia,
11(3), 287–296. https://doi.org/10.1590/1980-57642016dn11-030011
39.
Moyer-MileurL. J.RansdellL.BruggersC. S. (2009).
Fitness of children with standard-risk acute lymphoblastic leukemia during maintenance therapy: Response to a home-based exercise and nutrition program. Journal of Pediatric Hematology/Oncology,
31(4), 259–266. https://doi.org/10.1097/MPH.0b013e3181978fd4
40.
MurattM. D.PerondiM. B.GreveJ. M.RoschelH.PintoA. L.GualanoB. (2011).
Strength capacity in young patients who are receiving maintenance therapy for acute lymphoblastic leukemia: A case-control study. Clinics (Sao Paulo, Brazil),
66(7), 1277–1281. https://doi.org/10.1590/s1807-59322011000700026
41.
NaglieriJ.DasJ. P. (1997). Cognitive assessment system administration and scoring manual.
Riverside.
42.
NardesF.AraújoA. P. D. Q. C.RibeiroM. G.BittarM.GomesH. F. (2020).
The Mini-Mental state examination (MMSE) as a cognitive screening tool in duchenne muscular dystrophy. Annals of Child Neurology,
28(2), 57–65. https://doi.org/10.26815/acn.2020.00052
43.
NessK. K.KasteS. C.ZhuL.PuiC. H.JehaS.NathanP. C.InabaH.Wasilewski-MaskerK.ShahD.WellsR. J.KarlageR. E.RobisonL. L.CoxC. L. (2015).
Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia. Leukemia & Lymphoma,
56(4), 1004–1011. https://doi.org/10.3109/10428194.2014.944519
44.
OswaldK. A.BoJ. (2020).
Motor functioning and associated cognitive outcomes in pediatric survivors of acute lymphoblastic leukemia. Child Neuropsychology: A Journal on Normal and Abnormal Development in Childhood and Adolescence,
26(5), 597–611. https://doi.org/10.1080/09297049.2019.1676406
45.
OuvrierR.GoldsmithR.OuvrierS.WilliamsI. C. (1993).
The value of the Mini-Mental state examination in childhood: A preliminary study. Journal of Child Neurology,
8(2), 145–148. https://doi.org/10.1177/088307389300800206
46.
PevianiV.ScarpaP.VedovelliS.BottiniG. (2020).
Mini-Mental state pediatric examination (MMSPE) standardization and normative data on Italian children aged 36 to 72 months. Applied Neuropsychology Child,
9(1), 92–96. https://doi.org/10.1080/21622965.2018.1522590
47.
PuiC. H.RellingM. V.SandlundJ. T.DowningJ. R.CampanaD.EvansW. E. (2004).
Rationale and design of total therapy study XV for newly diagnosed childhood acute lymphoblastic leukemia. Annals of Hematology,
83(1), 124–126. https://doi.org/10.1007/s00277-004-0850-2.
48.
RamchandrenS.LeonardM.ModyR. J.DonohueJ. E.MoyerJ.HutchinsonR.GurneyJ. G. (2009).
Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia. Journal of the Peripheral Nervous System,
14(3), 184–189. https://doi.org/10.1111/j.1529-8027.2009.00230.x
49.
ReddickW. E.ConklinH. M. (2010).
Impact of acute lymphoblastic leukemia therapy on attention and working memory in children. Expert Review of Hematology,
3(6), 655–659. https://doi.org/10.1586/ehm.10.65
50.
Reinders‐MesselinkH. A.SchoemakerM. M.HofteM.GöekenL. N.KingmaA.van den BrielM. M.KampsW. A. (1996).
Fine motor and handwriting problems after treatment for childhood acute lymphoblastic leukemia. Pediatric Blood & Cancer,
27(6), 551–555. https://doi.org/10.1002/(SICI)1096-911X(199612)27:6<551::AID-MPO8>3.0.CO;2-K
51.
Reinders‐Messelink, H. A., Schoemaker, M., Snijders, T., Göeken, L., van den Briel, M., Bökkerink, J., & Kamps, W. (1999).
Motor performance of children during treatment for acute lymphoblastic leukemia. Medical and Pediatric Oncology,
33(6), 545–550. https://doi.org/10.1002/(sici)1096-911x(199912)33:6<545::aid-mpo4>3.0.co;2-y
52.
Rubial-AlvarezS.MachadoM. C.SintasE.de SolaS.BohmP.Pena-CasanovaJ. (2007).
A preliminary study of the mini-mental state examination in a Spanish child population. Journal of Child Neurology,
22(11), 1269–1273. http://doi.org/10.1177/0883073807307098
53.
SalvadorL. D. S.MouraR.FerreiraF. O.AndradeP. M. O.CarvalhoM. R. S.HaaseV. G. (2019).
The Mini-Mental examination for children (MMC): Evidence of validity for children with learning difficulties. Dementia & Neuropsychologia,
13(4), 427–435. http://dx.doi.org/10.1590/1980-57642018dn13-040010
54.
ShahA. J.EpportK.AzenC.KillenR.WilsonK.De ClerckD.CrooksG.KapoorN.KohnD. B.ParkmanR.WeinbergK. I. (2008).
Progressive declines in neurocognitive function among survivors of hematopoietic stem cell transplantation for pediatric hematologic malignancies. Journal of Pediatric Hematology/Oncology,
30(6), 411–418. https://doi.org/10.1097/MPH.0b013e318168e750
55.
SmithY. A.HongE.PressonC. (2000).
Normative and validation studies of the nine-hole peg test with children. Perceptual and Motor Skills,
90(3 Pt 1), 823–843. https://doi.org/10.2466/pms.2000.90.3.823
56.
SonodaT.TashiroY.SuzukY.KajiwaraY.ZeidanH.YokotaY.KawagoeM.NakayamaY.BitoT.ShimouraK.TatsumiM.NakaiK.NishidaY.YoshimiS.AoyamaT. (2018).
Relationship between agility and lower limb muscle strength, targeting university badminton players. Journal of Physical Therapy Science,
30(2), 320–323. https://doi.org/10.1589/jpts.30.320
57.
SpieglerB. J.KennedyK.MazeR.GreenbergM. L.WeitzmanS.HitzlerJ. K.NathanP. C. (2006).
Comparison of long-term neurocognitive outcomes in young children with acute lymphoblastic leukemia treated with cranial radiation or high-dose or very high-dose intravenous methotrexate. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology,
24(24), 3858–3864. https://doi.org/101200/JCO.2006.05.9055
58.
ToplakM. E.WestR. F.StanovichK. E. (2013).
Practitioner review: Do performance-based measures and ratings of executive function assess the same construct?Journal of Child Psychology and Psychiatry, and Allied Disciplines,
54(2), 131–143. https://doi.org/10.1111/jcpp.12001
59.
TsantaliE.EconomidisD.RigopoulouS.PorpodasC. (2012).
Comparison of cognitive performance in mild cognitive impairment and dementia patients with that in normal children and adults. Geriatrics & Gerontology International,
12(2), 336–344. https://doi.org/10.1111/j.1447-0594.2011.00744.x
60.
VainionpääL.KovalaT.TolonenU.LanningM. (1995).
Vincristine therapy for children with acute lymphoblastic leukemia impairs conduction in the entire peripheral nerve. Pediatric Neurology,
13(4), 314–318. https://doi.org/10.1016/0887-8994(95)00191-3
61.
WakefieldC. E.McLooneJ.GoodenoughB.LenthenK.CairnsD. R.CohnR. J. (2010).
The psychosocial impact of completing childhood cancer treatment: A systematic review of the literature. Journal of Pediatric Psychology,
35(3), 262–274. https://doi.org/10.1093/jpepsy/jsp056
62.
WechslerD. (1991). The Wechsler intelligence scale for children: Third edition.
The Psychological Corporation.
63.
WechslerD. (2014). The Wechsler intelligence scales for children: Fifth edition.
The Psychological Corporation.
