1Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
2Department of Neurology, Jeonbuk National University Hospital, Jeonju, Korea
3Department of Neurosurgery, Soonchunhyang University Seoul Hospital, Seoul, Korea
4Department of Neurology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Korea
5Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
6Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
7Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Copyright © 2022 The Korean Movement Disorder Society
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Conflicts of Interest
Kyung Ah Woo, Seung-Ho Jeon, Kye Won Park, Seung Hyun Lee, Hye Ran Park, Jong-Hee Chae, and Sun Ha Paek have nothing to disclose.
Han-Joon Kim received research grants from Seoul National University Hospital, Institute of Information and Communications Technology Planning and Evaluation, Forest Hills, and HLB Pharmaceutical.
Sun Ju Chung was supported by a grant from the Korea Healthcare Technology R & D Project, Ministry of Health & Welfare, Republic of Korea (HI19C0256).
Beomseok Jeon received research grants from Kuhnil Pharmaceutical, Peptron, Novartis Korea, Ipsen Korea, Samil Pharmaceutical, Abbvie Korea, Seoul National University Hospital Research Fund, Seoul National University College of Medicine, and Korean Brain Research Institute.
Funding Statement
None
Author Contributions
Conceptualization: Han-Joon Kim. Data curation: Kyung Ah Woo, Han-Joon Kim, Seung-Ho Jeon, Hye Ran Park, Kye Won Park, Seung Hyun Lee, Sun Ju Chung, Jong-Hee Chae. Formal analysis: Kyung Ah Woo, Han-Joon Kim. Investigation: Kyung Ah Woo, Han-Joon Kim. Methodology: Kyung Ah Woo, Han-Joon Kim. Project administration: Han-Joon Kim. Supervision: Han-Joon Kim. Writing—original draft: Kyung Ah Woo, Han-Joon Kim. Writing—review & editing: Han-Joon Kim, Kye Won Park, Seung Hyun Lee, Sun Ju Chung, Jong-Hee Chae, Sun Ha Paek, Beomseok Jeon.
Patients |
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A | B | C | D | E | F | G | H | I | J | |
Sex | F | F | M | M | M | F | M | M | M | M |
Onset age (yr) | 9 | 1 | 2 | 2 | 2 | 11 | 15 | 21 | 25 | 45 |
DBS age (yr) | 10 | 7 | 9 | 10 | 13 | 18 | 16 | 26 | 54 | 47 |
PKAN type | Classic | Classic | Classic | Classic | Classic | Unknown | Atypical | Atypical | Atypical | Atypical |
Family history | None | Sister of C | Brother of B | Younger brother with PANK2 mut | Younger brother died of HSD | None | Younger brother with PANK2 mut | None | Unclear | None |
Clinical course (age, yr) | Falling → generalized dystonia, bedridden (10) | Dev delay → tiptoeing (5) → generalized dystonia, bedridden (6) | Dev delay → tiptoeing (6) → generalized dystonia (8) | MR → tiptoeing (8) → generalized dystonia (10) | Language delay, falling → generalized dystonia (9) | Rt. hand dystonia → craniocervical & limbs dystonia over years | Rt. hand dystonia → generalized dystonia (16) | Rt. arm dystonia | Writer’s cramp → propagation to all limbs over 20 years | Rt. arm dystonic tremor, jaw dystonia, slowly progressive |
Mild dystonia in both legs | ||||||||||
Limb/Truncal dystonia | +/+ | +/+ | +/+ | +/+ | +/+ | +/- | +/+ | +/- | +/+ | +/- |
Dysphagia | + | + | + | + | + | + | + | - | + | - |
Cognitive impairment | + | + | + | + | + | + | + | - | - | - |
Other findings | Respiratory failure, retinopathy | Severe retrocollis | Scoliosis | Status dystonicus | Choreoathetosis | Severe dystonic posturing | Impulse control disorder | Rt. arm myoclonus, tremor | Weakness, both legs | Both hands tremor |
Medical treatments | TBZ, DZP | THX, DZP | THX, DZP | MDZ civ, DZP, QTP, THX, HPD | DZP, THX, ZNS, BCF, CNZ, HPD | CNZ, THX | THX, CNZ, BCF | DZP, THX, BCF | ALP, BCF, CNZ, THX, Levodopa | CNZ, THX, ECT |
DBS date | Sep 2010 | Jul 2015 | Sep 2015 | Oct 2012 | Dec 2007 | Jan 2015 | Jul 2009 | Nov 2011 | May 2009 | Feb 2019 |
Length of follow-up | ||||||||||
BFMDRS (mo) | 120 | 60 | 60 | 45 | 12 | 6 | 84 | 72 | 24 | 24 |
Clinical follow-up (mo) | 128 (FU+) | 71 (FU+) | 69 (FU+) | 56 (FU lost) | 27 (Expired) | 75 (FU+) | 100 (FU lost) | 78 (FU lost) | 62 (FU lost) | 24 (FU+) |
Last status | Bedridden | Assisted gait | Wheelchair ambulation | Assisted gait | Expired | Assisted gait | Assisted gait | Independent | Assisted gait | Independent |
Major clinical events and surgery-related adverse events (mo) | Status dystonicus (1 mo) | Wound dehiscence and infection (1 mo) | Brain abscess s/p Lt. electrode removal (5 mo) | Recurrent wound dehiscence and MRSA infection s/p wound revision, s/p DBS removal (19 mo) | Pneumonia (23 mo) followed by sepsis and status | Hospitalized due to painful dystonia (62 mo) | Blepharospasm (4 day, reversed) | None | Aggravation of dystonia (40 mo) | None |
Respiratory failure (22 mo) | s/p wound revision, Rt. hip subluxation s/p operation (34 mo) | Recurrent seizure with polyspike-andwaves, both frontotemporal (43 mo) | s/p GKS, both GPi (20 mo) | Dystonicus (27 mo) | Improved after battery change | Jaw opening dystonia and falling (54 mo) | Improved after battery change, hospitalized due to limb tremor aggravation (62 mo) | |||
Improved after battery change | ||||||||||
Stimulation parameters (Rt.)* | 4.3 V, 120 μs/60 Hz | 3.0 V, 60 μs/130 Hz | 3.3 V, 60 μs/90 Hz | - | 2.6 V, 120 μs/185 Hz | 4.1 V, 60 μs/130 Hz | 3.5 V, 60 μs/130 Hz | 3.2 V, 90 μs/130 Hz | 2.6 V, 90 μs/130 Hz | 2.0 V, 60 μs/130 Hz |
Stimulation parameters (Lt.)* | 4.5 V, 120 μs/60 Hz | 3.5 V, 60 μs/130 Hz | - | - | 2.8 V, 120 μs/185 Hz | 4.2 V, 60 μs/130 Hz | 3.5 V, 60 μs/130 Hz | 3.2 V, 90 μs/130 Hz | 3.6 V, 120 μs/130 Hz | 2.1 V, 60 μs/130 Hz |
* stimulation parameters provided in voltage stimulation, pulse width, and frequency; the last stimulation parameters are provided.
F, female; M, male; DBS, deep brain stimulation; PKAN, pantothenate kinase-associated neurodegeneration; mut, mutation; HSD, Hallervorden-Spatz disease; Dev delay, developmental delay; MR, mental retardation; Rt., right; TBZ, tetrabenazine; DZP, diazepam; THX, trihexyphenidyl; MDZ civ, midazolam continuous intravenous infusion; QTP, quetiapine; HPD, haloperidol; ZNS, zonisamide; BCF, baclofen; CNZ, clonazepam; ALP, alprazolam; ECT, electroconvulsive therapy; BFMDRS, Burke–Fahn–Marsden Dystonia Rating Scale; FU, follow-up; s/p, status post; Lt., left; MRSA, methicillin-resistant Staphylococcus aureus; GKS, gamma-knife surgery; GPi, globus pallidus internus.