Skip to main content
SpringerLink
Log in

Neuronale Plastizität und Neuromodulation in der Kinderneurologie

Neuronal plasticity and neuromodulation in pediatric neurology

  • Leitthema
  • Published:
Der Nervenarzt Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Neuronale Plastizität ist ein zentraler Mechanismus von Lernen und Erinnerung. Beeinträchtigungen neuronaler Plastizität werden als zentraler pathophysiologischer Mechanismus einer Vielzahl neuropädiatrischer und neurologischer Krankheitsbilder diskutiert.

Fragestellung

Möglichkeiten und Perspektiven des Einsatzes der Neuromodulation bei neuropädiatrischen und neurologischen Erkrankungen mit veränderter neuronaler Plastizität.

Material und Methoden

Darstellung und Diskussion der Untersuchungen neuronaler Plastizität bei Patienten mit Entwicklungsstörungen anhand eigener Arbeiten bei Patienten mit RASopathien, Autismus-Spektrum-Störung (ASS) und Gilles-de-la-Tourette-Syndrom (GTS).

Ergebnisse

Neurophysiologische Untersuchungen von Patienten mit RASopathien, ASS und GTS untermauern die pathophysiologische Relevanz abnormer neuronaler Plastizität bei diesen Erkrankungen. Die transkranielle Magnetstimulation (TMS) findet dabei als neuromodulatives Verfahren Anwendung und kann sowohl in der Evaluation als auch Induktion neuronaler Plastizität eingesetzt werden.

Diskussion

Neuronale Plastizität scheint ein wesentlicher pathophysiologischer Faktor bei Entwicklungsstörungen zu sein. Für den Einsatz bei Kindern mit neuropädiatrischen Krankheitsbildern eröffnen innovative Techniken neue Möglichkeiten für eine individualisierte TMS-Anwendung.

Abstract

Background

Neuronal plasticity is a core mechanism for learning and memory. Abnormal neuronal plasticity has emerged as a key mechanism in many neurological and neuropediatric diseases.

Objective

Chances and perspectives of neuromodulation techniques in neurological and neuropediatric diseases with altered neuronal plasticity.

Material and methods

Presentation and discussion of own results of neuronal plasticity investigations in patients with neurodevelopmental disorders including RASopathies, autism spectrum disorders (ASD) and Gilles de la Tourette syndrome (GTS).

Results

The results of neuronal plasticity studies in patients with RASopathies, ASD and GTS underline the pathophysiological relevance of abnormal neuronal plasticity in these diseases. Transcranial magnetic stimulation (TMS) is a useful tool to examine and also induce neuronal plasticity in these patients.

Conclusion

Neuronal plasticity appears to be an important pathophysiological factor in neuronal developmental disorders and can be investigated using TMS. New and innovative techniques may offer novel approaches for individualized TMS applications, particularly in children with neuropediatric conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. Feldman DE (2009) Synaptic mechanisms for plasticity in neocortex. Annu Rev Neurosci 32:33–55

    Article  CAS  Google Scholar 

  2. Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol (Lond) 232(2):331–356

    Article  CAS  Google Scholar 

  3. Ismail FY, Fatemi A, Johnston MV (2017) Cerebral plasticity: windows of opportunity in the developing brain. Eur J Paediatr Neurol 21(1):23–48

    Article  Google Scholar 

  4. Mall V, Berweck S, Fietzek UM, Glocker FX, Oberhuber U, Walther M et al (2004) Low level of intracortical inhibition in children shown by transcranial magnetic stimulation. Neuropediatrics 35(2):120–125

    Article  CAS  Google Scholar 

  5. Mainberger F, Langer S, Mall V, Jung NH (2016) Impaired synaptic plasticity in RASopathies: a mini-review. J Neural Transm 123(10):1133–1138

    Article  CAS  Google Scholar 

  6. Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R et al (2015) Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol 126(6):1071–1107

    Article  CAS  Google Scholar 

  7. Huang YZ, Lu MK, Antal A, Classen J, Nitsche M, Ziemann U et al (2017) Plasticity induced by non-invasive transcranial brain stimulation: a position paper. Clin Neurophysiol 128(11):2318–2329

    Article  Google Scholar 

  8. Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005) Theta burst stimulation of the human motor cortex. Neuron 45(2):201–206

    Article  CAS  Google Scholar 

  9. Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J (2000) Induction of plasticity in the human motor cortex by paired associative stimulation. Brain 123(Pt 3):572–584

    Article  Google Scholar 

  10. Jung NH, Gleich B, Gattinger N, Hoess C, Haug C, Siebner HR et al (2016) Quadri-pulse theta burst stimulation using ultra-high frequency bursts – A new protocol to induce changes in cortico-spinal excitability in human motor cortex. PLoS ONE 11(12):e168410

    Article  Google Scholar 

  11. Allen CH, Kluger BM, Buard I (2017) Safety of transcranial magnetic stimulation in children: a systematic review of the literature. Pediatr Neurol 68:3–17

    Article  Google Scholar 

  12. Rossi S, Hallett M, Rossini PM, Pascual-Leone A (2009) Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 120(12):2008–2039

    Article  Google Scholar 

  13. Juenger H, Kuhnke N, Braun C, Ummenhofer F, Wilke M, Walther M et al (2013) Two types of exercise-induced neuroplasticity in congenital hemiparesis: a transcranial magnetic stimulation, functional MRI, and magnetoencephalography study. Dev Med Child Neurol 55(10):941–951

    Article  Google Scholar 

  14. Kirton A, Andersen J, Herrero M, Nettel-Aguirre A, Carsolio L, Damji O et al (2016) Brain stimulation and constraint for perinatal stroke hemiparesis: the PLASTIC CHAMPS Trial. Neurology 86(18):1659–1667

    Article  CAS  Google Scholar 

  15. Rauen KA (2013) The RASopathies. Annu Rev Genomics Hum Genet 14:355–369

    Article  CAS  Google Scholar 

  16. Zenker M (2011) Clinical manifestations of mutations in RAS and related intracellular signal transduction factors. Curr Opin Pediatr 23(4):443–451

    Article  CAS  Google Scholar 

  17. Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, Ohno M et al (2002) Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415(6871):526–530

    Article  CAS  Google Scholar 

  18. Li W, Cui Y, Kushner SA, Brown RA, Jentsch JD, Frankland PW et al (2005) The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr Biol 15(21):1961–1967

    Article  CAS  Google Scholar 

  19. Lee YS, Ehninger D, Zhou M, Oh JY, Kang M, Kwak C et al (2014) Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome. Nat Neurosci 17(12):1736–1743

    Article  CAS  Google Scholar 

  20. Mainberger F, Jung NH, Zenker M, Wahllander U, Freudenberg L, Langer S et al (2013) Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1. BMC Neurol 13:131

    Article  Google Scholar 

  21. Mainberger F, Zenker M, Jung NH, Delvendahl I, Brandt A, Freudenberg L et al (2013) Impaired motor cortex plasticity in patients with Noonan syndrome. Clin Neurophysiol 124(12):2439–2444

    Article  Google Scholar 

  22. Association AP (2013) Diagnostic and statistical manual of mental disorders, 5. Aufl. American Psychiatric Association, Washington, DC.

    Book  Google Scholar 

  23. Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcin C et al (2012) Global prevalence of autism and other pervasive developmental disorders. Autism Res 5(3):160–179

    Article  Google Scholar 

  24. Krumm N, Turner TN, Baker C, Vives L, Mohajeri K, Witherspoon K et al (2015) Excess of rare, inherited truncating mutations in autism. Nat Genet 47(6):582–588

    Article  CAS  Google Scholar 

  25. Bourgeron T (2015) From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat Rev Neurosci 16(9):551–563

    Article  CAS  Google Scholar 

  26. Jung NH, Janzarik WG, Delvendahl I, Munchau A, Biscaldi M, Mainberger F et al (2013) Impaired induction of long-term potentiation-like plasticity in patients with high-functioning autism and Asperger syndrome. Dev Med Child Neurol 55(1):83–89

    Article  Google Scholar 

  27. Mostofsky SH, Powell SK, Simmonds DJ, Goldberg MC, Caffo B, Pekar JJ (2009) Decreased connectivity and cerebellar activity in autism during motor task performance. Brain 132(Pt 9):2413–2425

    Article  Google Scholar 

  28. Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J et al (2010) Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 468(7321):263–269

    Article  CAS  Google Scholar 

  29. Biscaldi M, Rauh R, Irion L, Jung NH, Mall V, Fleischhaker C et al (2014) Deficits in motor abilities and developmental fractionation of imitation performance in high-functioning autism spectrum disorders. Eur Child Adolesc Psychiatry 23(7):599–610

    Article  Google Scholar 

  30. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington, DC

    Book  Google Scholar 

  31. Jankovic J (1997) Tourette syndrome. Phenomenology and classification of tics. Neurol Clin 15(2):267–275

    Article  CAS  Google Scholar 

  32. Paszek J, Pollok B, Biermann-Ruben K, Muller-Vahl K, Roessner V, Thomalla G et al (2010) Is it a tic? – Twenty seconds to make a diagnosis. Mov Disord 25(8):1106–1108

    Article  Google Scholar 

  33. Brandt VC, Niessen E, Ganos C, Kahl U, Baumer T, Munchau A (2014) Altered synaptic plasticity in Tourette’s syndrome and its relationship to motor skill learning. PLoS ONE 9(5):e98417

    Article  Google Scholar 

  34. Delorme C, Salvador A, Valabregue R, Roze E, Palminteri S, Vidailhet M et al (2016) Enhanced habit formation in Gilles de la Tourette syndrome. Brain 139(Pt 2):605–615

    Article  Google Scholar 

  35. Franzkowiak S, Pollok B, Biermann-Ruben K, Sudmeyer M, Paszek J, Thomalla G et al (2012) Motor-cortical interaction in Gilles de la Tourette syndrome. PLoS ONE 7(1):e27850

    Article  CAS  Google Scholar 

  36. Arai N, Muller-Dahlhaus F, Murakami T, Bliem B, Lu MK, Ugawa Y et al (2011) State-dependent and timing-dependent bidirectional associative plasticity in the human SMA-M1 network. J Neurosci 31(43):15376–15383

    Article  CAS  Google Scholar 

  37. Tübing J, Gigla B, Brandt VC, Verrel J, Weissbach A, Beste C et al. (im Druck) Associative plasticity in supplementary motor area – motor cortex pathways in Tourette syndrome. Scientific Reports

  38. Gattinger N, Jung NH, Mall V, Gleich B (2018) Transcranial magnetic stimulation devices for biphasic and polyphasic ultra-high frequency protocols. Biol Eng Med. https://doi.org/10.15761/bem.1000136

    Article  Google Scholar 

Download references

Danksagung

Die Autoren danken allen Probanden, die an den Studien teilgenommen haben. A. Münchau wird durch die Deutsche Forschungsgemeinschaft unterstützt (Forschergruppe TEC4Tic; FOR 2698). Volker Mall erhält eine Förderung vom Bundesministerium für Bildung und Forschung (Förderkennzeichen: 01GM1519C). Nikolai H. Jung erhält eine Förderung der Deutschen Forschungsgemeinschaft (JU 3085/2-1).

Author information

Authors and Affiliations

  1. Fakultät für Medizin, Lehrstuhl für Sozialpädiatrie, Technische Universität München, Heiglhoftstr. 65, 81377, München, Deutschland

    N. H. Jung & V. Mall

  2. Institut für Neurogenetik, Universität zu Lübeck, Marie-Curie-Straße, 23562, Lübeck, Deutschland

    A. Münchau

Authors
  1. N. H. Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Münchau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Mall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. H. Jung.

Ethics declarations

Interessenkonflikt

N. H. Jung, A. Münchau und V. Mall geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jung, N.H., Münchau, A. & Mall, V. Neuronale Plastizität und Neuromodulation in der Kinderneurologie. Nervenarzt 89, 1131–1139 (2018). https://doi.org/10.1007/s00115-018-0586-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00115-018-0586-1

Schlüsselwörter

Keywords

Search

Navigation