Advertisement

Journal of Inherited Metabolic Disease

, Volume 36, Issue 6, pp 989–995 | Cite as

The brain in late-onset glycogenosis II: a structural and functional MRI study

  • Barbara Borroni
  • M. S. Cotelli
  • E. Premi
  • S. Gazzina
  • M. Cosseddu
  • A. Formenti
  • R. Gasparotti
  • M. Filosto
  • A. Padovani
Original Article

Abstract

Background

Late-onset glycogenosis type II (GSD II) is a rare, multisystem disorder mainly affecting limb and respiratory muscles due to acid alpha glucosidase deficiency. Despite evidence at autopsy of glycogen accumulation in the brain, no study exploring brain functions is yet available.

Objective

Our objective in this study was to assess brain changes in late-onset GSD II.

Methods

Each patient underwent a standardized neuropsychological assessment, regional grey-matter (GM) atrophy, and resting-state functional magnetic resonance imaging (RS-fMRI). Functional connectivity maps of the salience (SN) and default-mode (DMN) networks were considered. A group of age- and gender-matched healthy controls was enrolled for MRI comparisons. P values family-wise error (FWE) cluster level corrected inferior to 0.05 were considered.

Results

Nine GSD II patients (age 46.6 ± 8.0; 55 % male) were recruited. No significant GM atrophy was found in patients compared with controls (n = 18; age 48.0 ± 9.8,;40 % male). Functional connectivity within the SN was selectively reduced in patients, and cingulate gyrus and medial frontal cortex were mainly involved. Accordingly, patients had significant impairment of executive functions (as measured by Wisconsin Card Sorting test), whereas other cognitive domains were within mean normal ranges.

Conclusions

Our findings extend the clinical spectrum of GSD II by indicating that brain changes occur in this muscular disorder. Above all, these results should lead to better examinations of therapeutic approaches and perspectives for the affected patients. Further studies evaluating in depth these issues are warranted.

Keywords

Functional Connectivity Enzyme Replacement Therapy Glycogen Storage Disease Pompe Disease Salience Network 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors kindly thank Prof. C. Danesino from the Unit of Medical Genetics of University of Pavia, Italy, for conducting the genetic studies, and Dr. P. Tonin from the Department of Neurological, Neuropsychological, Morphological and Movement Sciences of University of Verona, Italy, for biochemical assay. We also thank the Italian Group for Glycogenosis II of the Italian Association of Myology.

Conflict of interest

None.

References

  1. American Association of Neuromuscular & Electrodiagnostic Medicine (2009) Diagnostic criteria for late-onset (childhood and adult) Pompe disease. Muscle Nerve 40:149–160CrossRefGoogle Scholar
  2. Angelini C, Semplicini C, Ravaglia S et al (2012) Observational clinical study in juvenile-adult glycogenosis type 2 patients undergoing enzyme replacement therapy for up to 4 years. J Neurol 259:952–958PubMedCrossRefGoogle Scholar
  3. Ashburner J, Friston KJ (2001) Why voxel-based morphometry should be used. NeuroImage 14:1238–1243PubMedCrossRefGoogle Scholar
  4. Ashburner J, Friston KJ (2005) Unified segmentation. NeuroImage 26:839–851PubMedCrossRefGoogle Scholar
  5. Begley DJ, Pontikis CC, Scarpa M (2008) Lysosomal storage diseases and the blood–brain barrier. Curr Pharm Des 14:1566–1580PubMedCrossRefGoogle Scholar
  6. Bembi B, Cerini E, Danesino C et al (2008) Diagnosis of glycogenosis type II. Neurology 71:S4–S11PubMedCrossRefGoogle Scholar
  7. Berg EA (1948) A simple objective technique for measuring flexibility in thinking. J Gen Psychol 39:15–22PubMedCrossRefGoogle Scholar
  8. Borroni B, Alberici A, Premi E et al (2008) Brain magnetic resonance imaging structural changes in a pedigree of asymptomatic progranulin mutation carriers. Rejuvenation Res 11:585–595PubMedCrossRefGoogle Scholar
  9. Braunsdorf WE (1987) Fusiform aneurysm of basilar artery and ectatic internal carotid arteries associated with glycogenosis type 2 (Pompe’s disease). Neurosurgery 21:748–749PubMedCrossRefGoogle Scholar
  10. Capitani E, Laiacona M (1997) Composite neuropsychological batteries and demographic correction: standardization based on equivalent scores, with a review of published data. The Italian Group for the Neuropsychological Study of Ageing. J Clin Exp Neuropsychol 19:795–809PubMedCrossRefGoogle Scholar
  11. Chien YH, Lee NC, Peng SF, Hwu WL (2006) Brain development in infantile-onset Pompe disease treated by enzyme replacement therapy. Pediatr Res 60:349–352PubMedCrossRefGoogle Scholar
  12. Craig AD (2002) How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci 3(8):655–666PubMedGoogle Scholar
  13. Craig AD (2009) Emotional moments across time: a possible neural basis for time perception in the anterior insula. Philos Trans R Soc Lond B Biol Sci 364(1525):1933–1942PubMedCrossRefGoogle Scholar
  14. De Luca M, Beckmann CF, De SN, Matthews PM, Smith SM (2006) fMRI resting state networks define distinct modes of long-distance interactions in the human brain. NeuroImage 29:1359–1367PubMedCrossRefGoogle Scholar
  15. Di Rocco M, Buzzi D, Taro M (2007) Glycogen storage disease type II: clinical overview. Acta Myol 26:42–44PubMedGoogle Scholar
  16. Dineen RA, Vilisaar J, Hlinka J et al (2009) Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis. Brain 132:239–249PubMedCrossRefGoogle Scholar
  17. Ebbink BJ, Aarsen FK, van Gelder CM et al (2012) Cognitive outcome of patients with classic infantile Pompe disease receiving enzyme therapy. Neurology 78:1512–1518PubMedCrossRefGoogle Scholar
  18. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198PubMedCrossRefGoogle Scholar
  19. Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8:700–711PubMedCrossRefGoogle Scholar
  20. Greicius MD, Krasnow B, Reiss AL, Menon V (2003) Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A 100:253–258PubMedCrossRefGoogle Scholar
  21. Isaacs B, Kennie AT (1973) The set test as an aid to the detection of dementia in old people. Br J Psychiatry 123:467–470PubMedCrossRefGoogle Scholar
  22. Jack RM, Gordon C, Scott CR, Kishnani PS, Bali D (2006) The use of acarbose inhibition in the measurement of acid alpha-glucosidase activity in blood lymphocytes for the diagnosis of Pompe disease. Genet Med 8:307–312PubMedCrossRefGoogle Scholar
  23. Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D (2006) A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 148:671–676PubMedCrossRefGoogle Scholar
  24. Laforet P, Petiot P, Nicolino M et al (2008) Dilative arteriopathy and basilar artery dolichoectasia complicating late-onset Pompe disease. Neurology 70:2063–2066PubMedCrossRefGoogle Scholar
  25. Menon V, Uddin LQ (2010) Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct 214(5–6):655–667PubMedCrossRefGoogle Scholar
  26. Mesulam MM (1998) From sensation to cognition. Brain 121(Pt 6):1013–1052PubMedCrossRefGoogle Scholar
  27. Peyron R, Laurent B, García-Larrea L (2000) Functional imaging of brain responses to pain. A review and meta-analysis. Neurophysiol Clin 30(5):263–288PubMedCrossRefGoogle Scholar
  28. Raben N, Plotz P, Byrne BJ (2002) Acid alpha-glucosidase deficiency (glycogenosis type II, Pompe disease). Curr Mol Med 2:145–166PubMedCrossRefGoogle Scholar
  29. Reitan RM (1955) The relation of the trail making test to organic brain damage. J Consult Psychol 19:393–394PubMedCrossRefGoogle Scholar
  30. Seeley WW, Menon V, Schatzberg AF et al (2007) Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 27(9):2349–2356PubMedCrossRefGoogle Scholar
  31. Spiridigliozzi GA, Heller JH, Kishnani PS (2012) Cognitive and adaptive functioning of children with infantile Pompe disease treated with enzyme replacement therapy: long-term follow-up. Am J Med Genet C Semin Med Genet 160:22–29CrossRefGoogle Scholar
  32. Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18:643–662CrossRefGoogle Scholar
  33. Sunderland T, Hill JL, Mellow AM et al (1989) Clock drawing in Alzheimer’s disease. A novel measure of dementia severity. J Am Geriatr Soc 37:725–729PubMedGoogle Scholar
  34. Taksir TV, Griffiths D, Johnson J, Ryan S, Shihabuddin LS, Thurberg BL (2007) Optimized preservation of CNS morphology for the identification of glycogen in the Pompe mouse model. J Histochem Cytochem 55:991–998PubMedCrossRefGoogle Scholar
  35. Thompson PM, Martin NG, Wright MJ (2010) Imaging genomics. Curr Opin Neurol 23:368–373PubMedGoogle Scholar
  36. van der Ploeg AT, Clemens PR, Corzo D et al (2010) A randomized study of alglucosidase alfa in late-onset Pompe’s disease. N Engl J Med 362:1396–1406PubMedCrossRefGoogle Scholar
  37. van der Walt JD, Swash M, Leake J, Cox EL (1987) The pattern of involvement of adult-onset acid maltase deficiency at autopsy. Muscle Nerve 10:272–281PubMedCrossRefGoogle Scholar
  38. Winkel LP, Hagemans ML, van Doorn PA et al (2005) The natural course of non-classic Pompe’s disease; a review of 225 published cases. J Neurol 252:875–884PubMedCrossRefGoogle Scholar
  39. Wokke JH, Escolar DM, Pestronk A et al (2008) Clinical features of late-onset Pompe disease: a prospective cohort study. Muscle Nerve 38:1236–1245PubMedCrossRefGoogle Scholar
  40. Zhou J, Greicius MD, Gennatas ED et al (2010) Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease. Brain 133:1352–1367PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Barbara Borroni
    • 1
  • M. S. Cotelli
    • 1
  • E. Premi
    • 1
    • 2
  • S. Gazzina
    • 1
  • M. Cosseddu
    • 1
  • A. Formenti
    • 1
  • R. Gasparotti
    • 3
  • M. Filosto
    • 1
  • A. Padovani
    • 1
  1. 1.Neurology UnitUniversity of BresciaBresciaItaly
  2. 2.Neurology UnitValleCamonica HospitalBresciaItaly
  3. 3.Neuroradiology UnitUniversity of BresciaBresciaItaly

Personalised recommendations