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Clinical course of patients with pantothenate kinase-associated neurodegeneration (PKAN) before and after DBS surgery

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Abstract

Introduction

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with a progressive clinical course. In addition to symptomatic therapy, DBS has been increasingly recognized as a potential therapeutic strategy, especially in severe cases. Therefore, we wanted to report our experience regarding benefits of DBS in five PKAN cases in 3-year follow-up study.

Methods

Five genetically confirmed PKAN patients from Serbia underwent GPi-DBS. To assess clinical outcome, we reviewed medical charts and applied: Schwab and England Activities of Daily Living Scale (S&E), EQ-5D questionnaire for quality of life, Patient Global Impression of Improvement (GPI-I), Functional Independence Measure (FIM), Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), Barry Albright Dystonia Scale (BAD). Patients were evaluated in five visits: at the disease onset, 5 years after the onset, before surgery, 6 months and 14–36 months after the surgery. Improvement of 20% was accepted as significant.

Results

Overall, dystonia significantly improved after GPi-DBS at 6 and 14–36 months postoperatively, when assessed by the BFMDRS and BAD. However, two patients failed to improve considerably. Four patients reported improvement on GPI-I, while one remained unchanged. Three patients reported significant improvement, when assessed with S&E and FIM. EQ-5D showed the most prominent improvement in the domains of mobility and pain/discomfort.

Conclusion

Three out of our five patients experienced beneficial effects of the GPi-DBS, in up to 36 months follow-up. Two patients who had not reached significant improvement had longer disease duration; therefore, it might be reasonable to recommend GPi-DBS as soon as dystonia became disabling.

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References

  1. Hayflick SJ, Shawn K, Westaway SK, Levinson B, Zhou B, Johnson MA et al (2003) Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med 348:33–40. https://doi.org/10.1056/NEJMoa020817

    Article  CAS  PubMed  Google Scholar 

  2. Hogarth P, Kurian M, Gregory A, Csányi B, Zagustin T, Kmiec T et al (2017) Consensus clinical management guideline for pantothenate kinase-associated neurodegeneration (PKAN). Mol Genet Metab 120(3):278–287. https://doi.org/10.1016/j.ymgme.2016.11.004

    Article  CAS  PubMed  Google Scholar 

  3. Hayflick SJ (2006) Neurodegeneration with brain iron accumulation: from genes to pathogenesis. Semin Pediatr Neurol 13:182–185. https://doi.org/10.1016/j.spen.2006.08.007

    Article  PubMed  Google Scholar 

  4. Tomić A, Petrović I, Svetel M, Dobričić V, Dragašević-Mišković N et al (2015) Pattern of disease progression in atypical form of pantothenatekinase-associated neurodegeneration (PKAN): prospective study. Parkinsonism Relat Disord 21:521–524. https://doi.org/10.1016/j.parkreldis.2015.02.006

    Article  PubMed  Google Scholar 

  5. Woon K, Tsegaye M, Vloeberghs MH (2007) The role of intrathecal baclofen in the management of primary and secondary dystonia in children. Br J Neurosurg 21:355–358. https://doi.org/10.1080/02688690701392899

    Article  CAS  PubMed  Google Scholar 

  6. Cossu G, Abbruzzese G, Matta G, Murgia D, Melis M, Ricchi V et al (2014) Efficacy and safety of deferiprone for the treatment of pantothenate kinase-associated neurodegeneration (PKAN) and neurodegeneration with brain iron accumulation (NBIA): results from a 4 years follow-up. Parkinsonism Relat Disord 20(6):651–654. https://doi.org/10.1016/j.parkreldis.2014.03.002

    Article  PubMed  Google Scholar 

  7. Pauls KA, Timmermann L (2012) Deep brain stimulation in pantothenate kinase associated neurodegeneration: challenges for the future. Eur J Neurol 19:533–534. https://doi.org/10.1111/j.1468-1331.2011.03585.x

    Article  CAS  PubMed  Google Scholar 

  8. Umemura A, Jaggi JL, Dolinskas CA, Stern MB, Baltuch GH (2004) Pallidal deep brain stimulation for longstanding severe generalized dystonia in Hallervorden-Spatz syndrome: case report. J Neurosurg 100:706–709. https://doi.org/10.3171/jns.2004.100.4.0706

    Article  PubMed  Google Scholar 

  9. Timmermann L, Pauls KA, Wieland K, Jech R, Kurlemann G, Sharma N et al (2010) Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation. Brain 133:701–712. https://doi.org/10.1093/brain/awq022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Castelnau P, Cif L, Valente EM, Vayssiere N, Hemm S, Gannau A et al (2005) Pallidal stimulation improves pantothenate kinase-associated neurodegeneration. Ann Neurol 57:738–741. https://doi.org/10.1002/ana.20457

    Article  PubMed  Google Scholar 

  11. Ge M, Zhang K, Ma Y, Meng FG, Hu WH, Yang AC et al (2011) Bilateral subthalamic nucleus stimulation in the treatment of neurodegeneration with brain iron accumulation type 1. Stereotact Funct Neurosurg 89(3):162–166. https://doi.org/10.1159/000323374

    Article  PubMed  Google Scholar 

  12. Shields DC, Sharma N, Gale JT, Eskandar EN (2007) Pallidal stimulation for dystonia in pantothenate kinase-associated neurodegeneration. Pediatr Neurol 37:442–445

    Article  Google Scholar 

  13. Mikati MA, Yehya A, Darwish H, Karam P, Comair Y (2009) Deep brain stimulation as a mode of treatment of early onset pantothenate kinase-associated neurodegeneration. Eur J Paediatr Neurol 13:61–64. https://doi.org/10.1016/j.pediatrneurol.2007.08.006

    Article  PubMed  Google Scholar 

  14. Garcia-Ruiz PJ, Ayerbe J, Vela Desojo L, Feliz CE, Del Val Fernandez J (2015) Deep brain stimulation for pantothenate kinase-associated neurodegeneration. Case Rep Neurol Med 2015:245735. https://doi.org/10.1155/2015/245735

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lim BC, Ki CS, Cho A, Hwang H, Kim KJ, Hwang YS et al (2012) Pantothenate kinase-associated neurodegeneration in Korea: recurrent R440P mutation in PANK2 and outcome of deep brain stimulation. Eur J Neurol 19:556–561. https://doi.org/10.1111/j.1468-1331.2011.03589.x

    Article  CAS  PubMed  Google Scholar 

  16. Mahoney R, Selway R, Lin JP (2011) Cognitive functioning in children with pantothenate-kinase-associated neurodegeneration undergoing deep brain stimulation. Dev Med Child Neurol 53:275–279. https://doi.org/10.1111/j.1469-8749.2010.03815.x

    Article  PubMed  Google Scholar 

  17. Adamovicová M, Jech R, Urgošík D, Spacková N, Krepelová A (2011) Pallidal stimulation in siblings with pantothenate kinase-associated neurodegeneration: 4-year follow-up. Mov Disord 26:184–187. https://doi.org/10.1002/mds.23349

    Article  PubMed  Google Scholar 

  18. Swaiman KF (2001) Hallervorden-Spatz syndrome. Pediatr Neurol 25:102–108

    Article  CAS  Google Scholar 

  19. Schwab RS, England AC (1969) Projection technique for evaluating surgery in Parkinson’s disease. In: Gillingham FJ, Donaldson MC (eds) Third symposium on Parkinson’s disease. Edinburgh, Livingston, pp 152–157

    Google Scholar 

  20. Brooks R (1996) EuroQol: the current state of play. Health Policy 37(1):53–72

    Article  CAS  Google Scholar 

  21. Guy W (ed) (1976) ECDEU assessment manual for psychopharmacology. Rockville, MD: US Department of Health, Education, and Welfare Public Health Service Alcohol, Drug Abuse, and Mental Health Administration.

  22. Keith RA, Granger CV, Hamilton BB, Sherwin FS (1987) The functional independence measure: a new tool for rehabilitation. Adv Clin Rehabil 1:6–18

    CAS  PubMed  Google Scholar 

  23. Burke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J (1985) Validity and reliability of a rating scale for the primary torsion dystonias. Neurology 35(1):73–77

    Article  CAS  Google Scholar 

  24. Barry MJ, Van Swearingen JM, Albright AL (1999) Realiability and responsiveness of the Barry-Albright dystonia scale. Dev Med Neurol 41(6):404–411

    Article  CAS  Google Scholar 

  25. Vidailhet M, Yelnik J, Lagrange C, Fraix V, Grabli D, Thobois S et al (2009) Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study. Lancet Neurol 8:709–717. https://doi.org/10.1016/S1474-4422(09)70151-6

    Article  PubMed  Google Scholar 

  26. Coubes P, Roubertie A, Vayssiere N, Hemm S, Echenne B (2000) Treatment of DYT1-generalised dystonia by stimulation of the internal globus pallidus. Lancet 355(9222):2220–2221. https://doi.org/10.1016/S0140-6736(00)02410-7

    Article  CAS  PubMed  Google Scholar 

  27. Dupre DA, Nangunoori R, Koduri S, Angle C, Cantella D, Whiting D (2018) Disease stabilization of DYT1-positive primary generalized dystonia with deep brain stimulation of the globus pallidus interna: A 15-year follow-up. Oper Neurosurg 14(5):597. https://doi.org/10.1093/ons/opx137

    Article  Google Scholar 

  28. De Vloo P, Lee DJ, Dallapiazza RF, Rohani M, Fasano A, Munhoz RP et al (2019) Deep brain stimulation for pantothenate kinase-associated neurodegeneration: a meta-analysis. Mov Disord 34(2):264–273

    Article  Google Scholar 

  29. Moro E, LeReun C, Krauss JK, Albanese A, Lin JP, Walleser Autiero S et al (2017) Efficacy of pallidal stimulation in isolated dystonia: a systematic review and meta-analysis. Eur J Neurol 24(4):552–560. https://doi.org/10.1111/ene.13255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sako W, Goto S, Shimazu H, Murase N, Matsuzaki K, Tamura T et al (2008) Bilateral deep brain stimulation of the globus pallidus internus in tardive dystonia. Mov Disord 23:1929–1931. https://doi.org/10.1002/mds.22100

    Article  PubMed  Google Scholar 

  31. Liu Z, Liu Y, Yang Y, Wang L, Dou W, Guo J et al (2017) Subthalamic nuclei stimulation in patients with pantothenate kinase-associated neurodegeneration (PKAN). Neuromodulation 20(5):484–491. https://doi.org/10.1111/ner.12549

    Article  PubMed  Google Scholar 

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Funding

This work was supported by Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant Number 175090).

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Authors and Affiliations

  1. Clinic of Neurology, Clinical Center of Serbia, Dr. Subotica 6, Belgrade, Serbia

    Marina Svetel, Aleksandra Tomić, Nataša Dragašević, Igor Petrović, Nikola Kresojević & Vladimir S. Kostić

  2. School of Medicine, University of Belgrade, Dr. Subotića starijeg 6, 11000, Belgrade, Serbia

    Marina Svetel, Aleksandra Tomić, Nataša Dragašević, Igor Petrović, Isidora Banjac, Jelena Vitković & Vladimir S. Kostić

  3. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital in Prague, Charles University, Prague, Czech Republic

    Robert Jech

  4. Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic

    Dušan Urgošik

  5. Institute for Human Genetics, School of Medicine, University of Belgrade, Belgrade, Serbia

    Ivana Novaković

Authors
  1. Marina Svetel
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  2. Aleksandra Tomić
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  3. Nataša Dragašević
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  4. Igor Petrović
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  6. Robert Jech
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  9. Jelena Vitković
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  11. Vladimir S. Kostić
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Corresponding author

Correspondence to Vladimir S. Kostić.

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Conflicts of interest

Marina Svetel has received speaker’s honoraria from Actavis. Robert Jech is Consultant to Ipsen, Cardion; Advisory Board of Ipsen. Vladimir Kostić has received research grants from the Ministry of Education, Science, and Technological Development, Republic of Serbia and the Serbian Academy of Science and Arts; and speaker honoraria from Actavis and Salveo. Aleksandra Tomić, Nataša Dragašević, Igor Petrović, Nikola Kresojević, Isidora Banjac, Jelena Vitković, Ivana Novaković and Dušan Urgošik declare no conflict of interest.

Ethical standards

The study was approved by the Institutional Review Board of the Clinic of Neurology and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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All patients gave informed consent.

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Svetel, M., Tomić, A., Dragašević, N. et al. Clinical course of patients with pantothenate kinase-associated neurodegeneration (PKAN) before and after DBS surgery. J Neurol 266, 2962–2969 (2019). https://doi.org/10.1007/s00415-019-09499-3

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  • DOI: https://doi.org/10.1007/s00415-019-09499-3

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