Clinical course of patients with pantothenate kinase-associated neurodegeneration (PKAN) before and after DBS surgery
- 97 Downloads
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.
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.
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.
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.
KeywordsDeep brain stimulation Dystonia Globus pallidus internus Pantothenate kinase-associated neurodegeneration
This work was supported by Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant Number 175090).
Compliance with ethical standards
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.
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.
All patients gave informed consent.
- 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 152–157Google 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.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 CrossRefPubMedGoogle 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 CrossRefGoogle Scholar