J Clin Neurol.  2018 Apr;14(2):153-157. 10.3988/jcn.2018.14.2.153.

Attention Deficit Hyperactivity Disorder in Neurofibromatosis Type 1: Evaluation with a Continuous Performance Test

• Cohen R
• Halevy A
• Aharon S
• Shuper A

• KMID: 2407940
• DOI: http://doi.org/10.3988/jcn.2018.14.2.153

Abstract

BACKGROUND AND PURPOSE
The objective of this study was to determine if the MOXO visual- and vocal-distractors-based continuous performance test distinguishes patients with attention deficit hyperactivity disorder (ADHD) and neurofibromatosis type 1 (NF1) from those without NF1.
METHODS
Thirty-five patients (16 males; mean age 9.91 years) attending a multidisciplinary NF1 clinic completed the MOXO test. The findings were compared to 532 healthy age-matched standardized control subjects (285 males) without ADHD.
RESULTS
The overall performance in the MOXO text was significantly worse in the NF1 group than in controls (p < 0.01), but no group-specific pattern was identified. Impulsivity and hyperactivity were significantly more prominent in males than females (p < 0.01). Compared to controls, the NF1 group exhibited significantly more failures to respond to target stimuli in the presence of visual distractors.
CONCLUSIONS
MOXO scores are abnormal in patients with NF1, but the test cannot differentiate between NF1 with ADHD characteristics and ADHD. The test highlights sex differences in ADHD characteristics in NF1. Overreactivity to visual distractors may form part of the attention deficit in NF1.

Keyword

attention deficit hyperactivity disorder; neurofibromatosis type 1; continuous performance test; MOXO

MeSH Terms

Attention Deficit Disorder with Hyperactivity*
Female
Humans
Impulsive Behavior
Male
Neurofibromatoses*
Neurofibromatosis 1*
Sex Characteristics

Figure

• 

  Fig. 1 Percentage of neurofibromatosis type 1 patients with z-scores of ≤1.65 according to age. A: attention, H: hyperactivity, I: impulsivity, T: timing.

Reference

1. Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL. Neurofibromatosis type 1 revisited. Pediatrics. 2009; 123:124–133. PMID: 19117870.

2. Rauen KA. The RASopathies. Annu Rev Genomics Hum Genet. 2013; 14:355–369. PMID: 23875798.

3. Acosta MT, Bearden CE, Castellanos FX, Cutting L, Elgersma Y, Gioia G, et al. The Learning Disabilities Network (LeaDNet): using neurofibromatosis type 1 (NF1) as a paradigm for translational research. Am J Med Genet A. 2012; 158A:2225–2232. PMID: 22821737.

4. Payne JM, Hyman SL, Shores EA, North KN. Assessment of executive function and attention in children with neurofibromatosis type 1: relationships between cognitive measures and real-world behavior. Child Neuropsychol. 2011; 17:313–329. PMID: 21347908.

5. Centers for Disease Control and Prevention (US). Attention Deficit Hyperactivity Disorder (ADHD) [Internet]. Atlanta (GA): CDC/National Center for Health Statistics;2017. cited 2018 Feb. Available from:https://www.cdc.gov/nchs/fastats/adhd.htm.

6. Miguel CS, Chaim-Avancini TM, Silva MA, Louzã MR. Neurofibromatosis type 1 and attention deficit hyperactivity disorder: a case study and literature review. Neuropsychiatr Dis Treat. 2015; 11:815–821. PMID: 25848279.

7. Descheemaeker MJ, Plasschaert E, Frijns JP, Legius E. Neuropsychological profile in adults with neurofibromatosis type 1 compared to a control group. J Intellect Disabil Res. 2013; 57:874–886. PMID: 23095048.

8. Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol. 1988; 45:575–578. PMID: 3128965.

9. Conners CK. Conners Comprehensive Behavior Rating Scales™. New York: Multi-Health Systems Inc.;2008.

10. Berger I, Goldzweig G. Objective measures of attention-deficit/hyperactivity disorder: a pilot study. Isr Med Assoc J. 2010; 12:531–535. PMID: 21287795.

11. Berger I, Slobodin O, Cassuto H. Usefulness and validity of continuous performance tests in the diagnosis of attention-deficit hyperactivity disorder children. Arch Clin Neuropsychol. 2017; 32:81–93. PMID: 28122767.

12. Berger I, Cassuto H. The effect of environmental distractors incorporation into a CPT on sustained attention and ADHD diagnosis among adolescents. J Neurosci Methods. 2014; 222:62–68. PMID: 24211249.

13. Cassuto H, Ben-Simon A, Berger I. Using environmental distractors in the diagnosis of ADHD. Front Hum Neurosci. 2013; 7:805. PMID: 24319423.

14. Dixon WJ. BMPD Statistical Software Manual. Berkeley: University of California Press;1990.

15. Ramtekkar UP, Reiersen AM, Todorov AA, Todd RD. Sex and age differences in attention-deficit/hyperactivity disorder symptoms and diagnoses: implications for DSM-V and ICD-11. J Am Acad Child Adolesc Psychiatry. 2010; 49:217–228. PMID: 20410711.

16. Nøvik TS, Hervas A, Ralston SJ, Dalsgaard S, Rodrigues Pereira R, Lorenzo MJ. ADORE Study Group. Influence of gender on attention-deficit/ hyperactivity disorder in Europe--ADORE. Eur Child Adolesc Psychiatry. 2006; 15(Suppl 1):I15–I24. PMID: 17177011.

17. Cohen R, Steinberg T, Kornreich L, Aharoni S, Halevy A, Shuper A. Brain imaging findings and social/emotional problems in Israeli children with neurofibromatosis type 1. Eur J Pediatr. 2015; 174:199–203. PMID: 25027832.

18. Lidzba K, Granström S, Lindenau J, Mautner VF. The adverse influence of attention-deficit disorder with or without hyperactivity on cognition in neurofibromatosis type 1. Dev Med Child Neurol. 2012; 54:892–897. PMID: 22881119.

19. Koth CW, Cutting LE, Denckla MB. The association of neurofibromatosis type 1 and attention deficit hyperactivity disorder. Child Neuropsychol. 2000; 6:185–194. PMID: 11402396.

20. Huijbregts S. Cognitive-behavioral phenotype or comorbid disorder? The case of attention-deficit-hyperactivity disorder in neurofibromatosis type 1. Dev Med Child Neurol. 2012; 54:873–874. PMID: 22881385.

21. Denckla MB, Hofman K, Mazzocco MM, Melhem E, Reiss AL, Bryan RN, et al. Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis-1. Am J Med Genet. 1996; 67:98–102. PMID: 8678124.

22. Hyman SL, Gill DS, Shores EA, Steinberg A, North KN. T2 hyperintensities in children with neurofibromatosis type 1 and their relationship to cognitive functioning. J Neurol Neurosurg Psychiatry. 2007; 78:1088–1091. PMID: 17299016.

23. Michael GA, Garcia S, Herbillon V, Lion-François L. Reactivity to visual signals in neurofibromatosis type 1: is everything ok? Neuropsychology. 2014; 28:423–428. PMID: 24274026.

24. Clements-Stephens AM, Rimrodt SL, Gaur P, Cutting LE. Visuospatial processing in children with neurofibromatosis type 1. Neuropsychologia. 2008; 46:690–697. PMID: 17988695.

25. Violante IR, Ribeiro MJ, Cunha G, Bernardino I, Duarte JV, Ramos F, et al. Abnormal brain activation in neurofibromatosis type 1: a link between visual processing and the default mode network. PLoS One. 2012; 7:e38785. PMID: 22723888.

26. Ribeiro MJ, d'Almeida OC, Ramos F, Saraiva J, Silva ED, Castelo-Branco M. Abnormal late visual responses and alpha oscillations in neurofibromatosis type 1: a link to visual and attention deficits. J Neurodev Disord. 2014; 6:4. PMID: 24559228.

27. Hughes SW, Crunelli V. Just a phase they're going through: the complex interaction of intrinsic high-threshold bursting and gap junctions in the generation of thalamic alpha and theta rhythms. Int J Psychophysiol. 2007; 64:3–17. PMID: 17000018.

28. Payne JM, Moharir MD, Webster R, North KN. Brain structure and function in neurofibromatosis type 1: current concepts and future directions. J Neurol Neurosurg Psychiatry. 2010; 81:304–309. PMID: 20185469.

29. Berger I, Slobodin O, Aboud M, Melamed J, Cassuto H. Maturational delay in ADHD: evidence from CPT. Front Hum Neurosci. 2013; 7:691. PMID: 24298243.

30. Shaw P, Malek M, Watson B, Sharp W, Evans A, Greenstein D. Development of cortical surface area and gyrification in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2012; 72:191–197. PMID: 22418014.