Globus pallidus internus deep brain stimulation (GPi‐DBS) is an established treatment for chorea and dystonia, including when due to neurodegenerative diseases. Chorea‐acanthocytosis is a rare autosomal recessive neurodegenerative disease characterized by adult‐onset chorea, involuntary orofacial movements, neuropsychiatric symptoms, and peripheral acanthocytes caused by VPS13A gene mutations. Although hyperkinetic symptoms respond to DBS, 1 , 2 neurodegeneration progresses despite GPi‐DBS, leading to a decline in activities of daily living (ADL). DBS maintenance remains necessary in late‐stage disease due to the presence of the implanted device and the need for symptom and battery status monitoring. Unlike in Parkinson's disease 3 , there is limited literature on GPi‐DBS discontinuation in hyperkinetic movement disorders is limited, as abrupt cessation may provoke dystonic storms. 4 We report two late‐stage chorea‐acanthocytosis cases where hyperkinetic symptoms did not relapse after GPi‐DBS withdrawal.
Case Report
Case 1
A 30‐year‐old man initially presented with epilepsy and hallucinations. By age 31, he developed involuntary movements, including tongue‐biting, which spread by age 32, along with truncal dystonia causing forward bending while walking. Genetic testing confirmed chorea‐acanthocytosis (see patient 15 in reference 5). GPi‐DBS was implemented, stopping tongue‐biting and improving truncal dystonia (reference 1, patient 6), sustained for five years. 1 Table 1 summarizes stimulation settings.
TABLE 1.
Therapeutic profiles of patients
| Case 1 | Case 2 | |
|---|---|---|
| Age at surgery, Sex | 32, Male | 48, Male |
| Initial electrode, IPG | Medtronic 3387, Soletra 7426 | Medtronic 3387, Soletra 7426 |
| Major stimulation settings |
Upon discharge following surgery: Lt: C + 1–2‐, 2.6 V, 60 μs, 170 Hz; Rt: C + 1–2‐, 2.6 V, 60 μs, 170 Hz At age 37, after reoperation (electrode changed to Medtronic 3389): Lt: C + 1–2‐, 3.3 V, 120 μs, 170 Hz; Rt: C + 1–2‐, 2.2 V, 120 μs, 170 Hz At age 42, before DBS withdrawal: Lt: C + 1–2‐, 2.5 V, 120 μs, 140 Hz; Rt: C + 1–2‐, 2.0 V 90 μs, 130 Hz |
Upon discharge following surgery: Lt: C + 1–2‐, 2.0 V, 60 μs, 130 Hz, rt: C + 1–2‐, 2.0 V, 60 μs, 130 Hz At age 57: Lt: C + 1–2‐, 3.0 V, 90 μs, 130 Hz; Rt: C + 1–2‐, 3.0 V, 90 μs, 130H At age 63, before DBS cessation: Lt: C + 1–2‐, 2.0 V 60 μs, 130 Hz; Rt: C + 1–2‐, 2.0 V, 60 μs, 130 Hz |
| Pharmacological management at DBS withdrawal | Levodopa, carbidopa hydrate 400 mg, amantadine 100 mg, carbamazepine 400 mg, valproic acid 900 mg | Levodopa, carbidopa hydrate 400 mg, valproic acid 900 mg, levetiracetam 1000 mg |
As parkinsonism became more prominent, we considered two factors: (1) stimulation‐dependent parkinsonism emerged, and (2) the phase characterized by predominant involuntary movements was nearing its end. Even with reduced stimulation, the involuntary movements did not worsen.
Abbreviations: IPG, implatable pulse generator; C, contact; DBS, deep brain stimulation; V, voltage; Lt, Left; Rt, Right.
At age 37, the patient's dystonia worsened, with forward neck and trunk bending, leading to reduced food intake. Magnetic resonance imaging (MRI) showed left electrode migration, and dystonia improved following electrode revision surgery (Fig. 1A, B). By age 39, residual involuntary movements of the mouth, face, and neck gradually declined despite no significant changes in the stimulation parameters. Hypokinesia, dysarthria, and frontal lobe dysfunction progressed, with no further involuntary movements. At 42, a fall‐related head injury caused speech decline, prompting hospital admission. MRI detected a brain abscess, necessitating abrupt DBS system removal. However, involuntary movements did not relapse. Muscle rigidity increased mildly, prompting an adjustment of levodopa (from 400 to 600 mg) and carbidopa (from 40 to 60 mg). MRI showed progressive putamen and caudate atrophy (Fig. 1C, D). The patient died at 43 from asphyxiation, with no recurrence of involuntary movements, including orofacial ones.
FIG. 1.
Brain MRI in Case 1. (A) Brain MRI at age 32. (B) Brain MRI at age 37, showing the left electrode migrating deeper (white arrow). (C) Brain MRI at age 32. (D) Brain MRI at age 42. Putamen and caudate atrophy are more pronounced, and the high‐intensity area near the putamen indicates edema linked to the abscess (white arrow).
Case 2
A 29‐year‐old man presented with epilepsy and dementia. By age 43, he developed involuntary orofacial movements, causing frequent tongue injuries requiring sutures and bite blocks at age 46. Severe truncal dystonia led to excessive forward bending. Genetic testing confirmed chorea‐acanthocytosis (see patient 17 in reference 5). GPi‐DBS at age 48 improved dystonia and orofacial involuntary movements, eliminating tongue‐biting (as described in reference 1, patient 5), 1 with benefits sustained for five years.
By age 53, residual involuntary movements gradually decreased while hypokinesia, dysphagia, and cognitive decline progressed. At age 55, involuntary movements had disappeared. At 63, the patient developed skin thinning and chronic inflammation around the right IPG. Based on Case 1, DBS was gradually discontinued over two weeks without symptom relapse (Video S1). Brain MRI showed progressive putamen and caudate atrophy. No relapse of involuntary movements, including tongue‐biting, was observed until he died suddenly five months later, before DBS system removal.
Discussion
This report demonstrates the long‐term efficacy of GPi‐DBS in chorea‐acanthocytosis and the feasibility of its safe discontinuation in late‐stage cases.
Our findings suggest that GPi‐DBS benefits may persist for more than five years in chorea‐acanthocytosis. Dystonia improvement is transient in neurodegenerative diseases such as pantothenate kinase‐associated neurodegeneration (PKAN) and Machado‐Joseph disease (MJD). 6 The persistence of stimulation effects depends on the neurodegenerative disease type.
Early in chorea‐acanthocytosis, hyperkinetic symptoms like chorea and dystonia dominate, but these shift towards hypokinetic symptoms in later stages. Two cases showed the disappearance of involuntary movements, leaving only parkinsonism after more than 15 years of progression. 7 In Case 1, involuntary movements recurred five years post‐DBS surgery due to electrode shifting but did not reappear after bilateral electrode removal a decade later. DBS requirements may evolve with disease progression, suggesting discontinuation might be feasible in certain late‐stage cases.
This shift from hyperkinetic to hypokinetic symptoms is also seen in other neurodegenerative diseases. In Huntington's disease, psychiatric symptoms, cognitive decline, and ataxia increase while chorea diminishes in later stages. 8 For DYT‐XDP (DYT3) patients, dystonia generalizes over 2–5 years, plateaus by the 10th year, and may lessen or transition to parkinsonism by the 15th. 9 Conversely, in DYT‐TOR1A (DYT1), DBS discontinuation often worsens dystonia, even after prolonged use. 10 The mechanism underlying involuntary movement reduction in some neurodegenerative diseases remains unclear. However, dystonia, a movement disorder involving abnormal neural circuits, may not manifest in the presence of extensive organic brain damage. To the best of our knowledge, evidence on safe DBS discontinuation in late‐stage neurodegenerative diseases is limited. Therapeutic strategies may need to adapt to the disease type and progression stage.
Author Roles
(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.
J.I.: 1A, 1B, 1C, 3A, 3B
A.I.: 1B, 1C, 3B
F.Y.: 1B, 1C
R.O.: 1B, 1C, 3B
T.K.: 1B, 1C, 3B
A.Y.: 1B, 1C, 3B
T.A.: 1B, 1C, 3B
S.K.: 1B, 1C, 3B
K.T.: 3B
Disclosures
Ethical Compliance Statement: The authors confirm that institutional review board approval was not required for this study. Additionally, we confirm that we have read the Journal's position on the issues involved in ethical publication and affirm that this work is consistent with these guidelines. We explained the use of patient videos in our article and obtained written informed consent.
Funding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare no conflicts of interest linked to this manuscript.
Financial Disclosures for the Previous 12 Months: Unrelated to this work, JI and FY received grants from InSightec, Ltd., for a trial on focused ultrasound for Parkinson's disease.
Supporting information
Supplementary Video S1. Case 2. With DBS turned off, the patient exhibited no recurrence of involuntary movements and displayed only parkinsonism. Notably, parkinsonian tremors were detected in the tongue, but no involuntary movements, such as tongue‐biting, were present.
Acknowledgments
The authors thank Dr. Makoto Taniguchi, former head of the Department of Neurosurgery at Tokyo Metropolitan Neurological Hospital, for treating Case 1. Dr Taniguchi sadly passed away in 2020.
We also sincerely thank Dr. Akira Sano of the Kagoshima University for conducting the VPS13A gene tests.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Video S1. Case 2. With DBS turned off, the patient exhibited no recurrence of involuntary movements and displayed only parkinsonism. Notably, parkinsonian tremors were detected in the tongue, but no involuntary movements, such as tongue‐biting, were present.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.