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

Svetel, Marina; Tomić, Aleksandra; Dragašević, Nataša; Petrović, Igor; Kresojević, Nikola; Jech, Robert; Urgošík, Dušan; Banjac, Isidora; Vitković, Jelena; Novaković, Ivana; Kostić, Vladimir

doi:10.1007/s00415-019-09499-3

Cited by 15 publications

(11 citation statements)

References 27 publications

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“…A meta-analysis on DBS [9] has shown that it could improve the dystonia movement scores in patients with PKAN one year postoperatively. Dystonia of three out of five patients improved after DBS up to 36 months postoperatively in a case series study [10]. Overall, DBS could initially improve the dystonia movement scores in some patients with PKAN but could not stop the disease progression.…”

Section: Discussionmentioning

confidence: 91%

Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: a single-arm, open-label study

Chang

Zhang

Jiang

et al. 2020

Orphanet J Rare Dis

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Objective This study aimed to explore the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN). Methods A single-arm, open-label study was conducted. All subjects received pantethine during the 24-week period of treatment. The primary endpoints were change of the Unified Parkinson’s Disease Rating Scale (UPDRS) I–III and Fahn–Marsden (FM) score from baseline to week 24 after treatment. Results Fifteen children with PKAN were enrolled, and all patients completed the study. After 24 weeks of treatment with pantethine at 60 mg/kg per day, there was no difference in either UPDRS I–III (t = 0.516, P = 0.614) or FM score (t = 0.353, P = 0.729) between the baseline and W24. Whereas the rates of increase in UPDRS I-III (Z = 2.614, p = 0.009) and FM scores (Z = 2.643, p = 0.008) were slowed. Four patients (26.7%) were evaluated as “slightly improved” by doctors through blinded video assessment. Patients with lower baseline UPDRS I–III or FM scores were more likely to be improved. The quality of life of family members improved after pantethine treatment, evaluated by PedsQL TM 2.0 FIM scores, whereas the quality of life of the patients was unchanged at W24, evaluated by PedsQL TM 4.0 and PedsQL TM 3.0 NMM. Serum level of CoA was comparable between baseline and W24. There was no drug related adverse event during the study. Conclusions Pantethine could not significantly improve motor function in children with PKAN after 24 weeks treatment, but it may delay the progression of motor dysfunction in our study. Pantethine was well-tolerated at 60 mg/kg per day. Trial registration Clinical trial registration number at www.chictr.org.cn:ChiCTR1900021076, Registered 27 January2019, the first participant was enrolled 30 September 2018, and other 14 participants were enrolled after the trial was registered.

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Section: Discussionmentioning

confidence: 91%

Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: a single-arm, open-label study

Chang

Zhang

Jiang

et al. 2020

Orphanet J Rare Dis

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show abstract

“…A meta-analysis on DBS [9] has shown that it could improve the dystonia movement scores in patients with PKAN one year postoperatively. Dystonia of three out of ve patients improved after DBS up to 36 months postoperatively in a case series study [10] . Overall, DBS could initially improve the dystonia movement scores in some patients with PKAN but could not stop the disease progression.…”

Section: Discussionmentioning

confidence: 93%

Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: A single-arm, open-label study.

Chang

Zhang

Jiang

et al. 2020

Preprint

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Objective This study aimed to explore the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN).Methods A single-arm, open-label study was conducted. All subjects received pantethine during the 24-week period of treatment. The primary endpoints were change of the Unified Parkinson’s Disease Rating Scale (UPDRS) I–III and Fahn–Marsden (FM) score from baseline to week 24 after treatment.Results Fifteen children with PKAN were enrolled, and all patients completed the study. After 24 weeks of treatment with pantethine at 60mg/kg per day, there was no difference in either UPDRS I–III (t=0.516, P=0.614) or FM score (t=0.353, P=0.729) between the baseline and W24. Whereas the rates of increase in UPDRS I-III (Z=2.614, p=0.009) and FM scores (Z=2.643, p=0.008) were slowed. Four patients (26.7%) were evaluated as “slightly improved” by doctors through blinded video assessment. Patients with lower baseline UPDRS I–III or FM scores were more likely to be improved. The quality of life of family members improved after pantethine treatment, evaluated by PedsQL TM 2.0 FIM scores, whereas the quality of life of the patients was unchanged at W24, evaluated by PedsQL TM 4.0 and PedsQL TM 3.0 NMM. Serum level of CoA was comparable between baseline and W24. There was no drug related adverse event during the study.Conclusions Pantethine could not significantly improve motor function in children with PKAN after 24 weeks treatment, but it may delay the progression of motor dysfunction in our study. Pantethine was well-tolerated at 60mg/kg per day.Trial registration:Clinical trial registration number at www.chictr.org.cn：ChiCTR1900021076，Registered 27 January2019，the first participant was enrolled 30 September 2018，and other 14 participants were enrolled after the trial was registered.

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“…A case series of five patients with PKAN reported improvement in dystonia 14-36 months postoperatively. 16 Two cases in a series by Castelnau et al 17 showed sustained improvement after 32 and 42 months, Adamovicová et al 18 described improvements of 24% and 51% after 4 years in two siblings, and Krause et al 19 described a 24% improvement after 5 years in one patient; however, in these three cases, secondary progression was observed after the first year. Compared with these previous observations, the present study provides supportive data for GPi-DBS over an extended follow-up period in a larger number of patients with genetically confirmed PKAN.…”

Section: Discussionmentioning

confidence: 96%

Long-Term Outcomes of Deep Brain Stimulation in Pantothenate Kinase-Associated Neurodegeneration-Related Dystonia

Woo

Kim²,

Jeon

et al. 2022

JMD

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ObjectiveaaTo investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN).MethodsaaWe reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre-and postoperative Burke-Fahn-Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected. Descriptive analysis was performed for BFMDRS-M scores, BFMDRS-D scores, and the orofacial, axial, and limb subscores of the BFMDRS-M at 6-12, 24-36, and 60-72 months postoperatively.ResultsaaFive classic-type, four atypical-type, and one unknown-type PKAN cases were identified. The mean preoperative BFMDRS-M score was 92.1 for the classic type and 38.5 for the atypical or unknown type, with a mean BFMDRS follow-up of 50.7 months and a clinical follow-up of 69.0 months. The mean improvements in BFMDRS-M score were 11.3%, 41.3%, and 30.5% at 6-12, 24-36, and 60-72 months, respectively. In four patients with full regular evaluations until 60-72 months, improvements in the orofacial, axial, and limb subscores persisted, but the disability scores worsened from 24-36 months post-operation compared to the baseline, mainly owing to the aggravation of eating and feeding disabilities.ConclusionaaThe benefits of GPi-DBS on dystonia may persist for more than 5 years in PKAN. The effects on patients' subjective disability may have a shorter duration despite improvements in dystonia owing to the complex manifestations of PKAN. KeywordsaaDeep brain stimulation (DBS); Dystonia; Globus pallidus; Neurodegeneration with brain iron accumulation (NBIA); Pantothenate kinase-associated neurodegeneration (PKAN).

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

Cited by 15 publications

References 27 publications

Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: a single-arm, open-label study

Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: a single-arm, open-label study

Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: A single-arm, open-label study.

Long-Term Outcomes of Deep Brain Stimulation in Pantothenate Kinase-Associated Neurodegeneration-Related Dystonia

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