Introduction

Deep brain stimulation (DBS) has become an accepted treatment for inherited and idiopathic dystonia but less so for acquired dystonia. There is growing evidence that the clinical benefit of DBS in dystonia can be sustained for 10 years or longer and that the long-term outcome may surpass short-term benefit. When stimulation is discontinued in the first years after stimulation, dystonic symptoms may recur rapidly [1]. A sustained effect, however, may be observed when stimulation is switched off after long term stimulation. While this phenomenon has been noted in patients with inherited or idiopathic dystonia [2, 3, 4], it has not received attention before in acquired generalized dystonia.

Case report

This 25-year-old man (early follow-up published elsewhere) [5] suffered from generalized acquired dystonia with choreoathetotic movements due to perinatal asphyxia. Upon clinical examination, he also had an action-induced tremor with myoclonic jerks, mild spastic tetraparesis and ataxic gait. He was wheelchair-bound for longer distances and was not able to drink or eat by himself independently. Furthermore, he had severe dysarthria. The Burke-Fahn-Marsden (BFM) motor score was 80.5 (assessing axial and more peripheral dystonic symptoms), disability score 19 (describing dystonia-related problems in daily life). The patient was under no specific medication.

He underwent implantation of quadripolar DBS electrodes (Model 3387; Medtronic Inc., Minneapolis) bilaterally in the ventral intermediate nucleus (Vim) of the thalamus and bilaterally in the posteroventral lateral globus pallidus internus (GPi) guided by CT-stereotactic surgery and microelectrode recording. Postoperative stereotactic CT demonstrated appropriate placement of all four electrodes. After test stimulation an implantable pulse generator (IPG) (Kinetra; Medtronic Inc., Minneapolis) was implanted and connected to the thalamic DBS electrodes. Postoperatively, he had improvement of tremor and dystonia, he was able to grip objects and was more independent (BFM motor score 67.5; disability score 15 at 17 months postoperatively). Stimulation settings and the further course are shown in Table 1.

Table 1

Time course of stimulation settings and adaptations according to the clinical evolution in a patient with DBS of the Vim and GPi for acquired dystonia and sustained clinical benefit after DBS switch-off.

MONTHS	TARGET/MODE	INTENSITY	FREQUENCY	PULSE WIDTH [µS]	CLINICAL OBSERVATION
POST-OP	ACTIVE CONTACTS	[V]	[HZ]
Pre-OP	NA	NA	NA	NA	BFM motor score 80.5 BFM disability score 19
Post-OP	Vim/bipolar	L 3,0; R 3,0	130 Hz	210 µs	improved fine motor skills and dysarthria
	(1–/2+; 5–/6+)
2 months	Vim/bipolar	L 3,2; R 3,2	130 Hz	210 µs	stable
	(1–/2+; 5–/6+)
8 months	Vim/bipolar	L 3,4; R 3,4	130 Hz	210 µs	improved gait (dystonic posture of legs) and dysarthria
	(1–/2+; 5–/6+)
17 months	Vim/bipolar	L 3,7; R 3,8	130 Hz	210 µs	BFM motor score 67.5
	(1–/2+; 5–/6+)				BFM disability score 15
30 months	Vim/bipolar	L 4,0; R 4,1	130 Hz	210 µs	stable
	(1–/2+; 5–/6+)
38 months	No stimulation	–	–	–	fine motor skills gait BFM motor score 71,5 BFM disability score 15
41 months	GPi/bipolar	L 4,0; R 4,0	130 Hz	210 µs	improved fine motor skills (e.g. smartphone use)
	(1–/2+; 5–/6+)
43 months	GPi/bipolar	L 4,3; R 4,3	130 Hz	210 µs	stable BFM motor score 67 BFM disability score 15
	(1–/2+; 5–/6+)
50 months	GPi/bipolar	L 4,7; R 3,9	130 Hz	210 µs	mild hypokinesia
	(1–/2+; 5–/6+)				gait
58 months	GPi/bipolar	L 4,5; R 3,9	130 Hz	210 µs	stable
	(1–/2+; 9–/10+)				IPG change
64 months	GPi/bipolar	L 4,5; R 3,8	130 Hz	210 µs	improved fine motor skills BFM motor score 67 BFM disability score 15
	(1–/2+; 9–/10+)
76 months	No stimulation	–	–	–	BFM motor score 67,5
					BFM disability score 15
105 months	No stimulation	–	–	–	BFM motor score 58,5 BFM disability score 13

After 38 months of Vim stimulation the IPG was replaced upon battery depletion, and the previously and simultaneously implanted pallidal electrodes were then connected to possibly obtain further benefit. The rationale were the phasic and dystonic symptoms of the extremities, especially with severe difficulties to put the feet with the sole on the ground, and cervical dystonia further affecting the ability to eat. While there was subjective improvement in fine motor skills (e.g. handling of his smartphone became somewhat easier), the BFM motor and disability scores remained unchanged (BFM motor score 67, disability score 15) compared to bilateral Vim stimulation (electrodes were disconnected but not removed).

When he was seen for a routine follow-up 76 months after implantation, there was stable improvement of dystonia. However, IPG check revealed battery depletion since 5 weeks ago. Since clinical symptoms were stable with still an improvement of about 15% in the BFM motor score compared to the preoperative situation, IPG replacement was postponed and he continued to do well. Two and a half years after battery depletion, both the BFM motor score (58,5) and the disability score (13) were even further improved. No confounding factors such as medication, life circumstances or additional treatments had been modified. In the further course, however, one and a half year later, he noted a mild deterioration of dystonia and the IPG was replaced, leading to a rapid improvement to the former level, which is now stable for more than a year.

Discussion

The mechanisms of chronic DBS in dystonia have not been fully clarified thus far. It appears that DBS does not only alter neuronal activity at the site of stimulation, but that it also has more widespread effects both on altered inhibition and neuroplasticity with a differing temporal profile [6, 7]. Furthermore, it may alter more specifically network activity as shown by its impact on local field potentials [8, 9].

Long-term efficacy of chronic DBS after several years has been shown in inherited and idiopathic dystonia for up to 10 years. The re-occurrence of dystonic symptoms after switching off of long-term chronic DBS has prospectively been studied in DYT 1 patients with GPi-DBS [6]. Patients had been stimulated for at least 5 years. Dystonic symptoms did not reach the preoperative severity, but remained at an intermediate level at 24 and 48 hours off stimulation. In 13 patients with GPi-DBS for primary generalized dystonia 4 patients remained at an intermediate level of symptom re-emergence after 48 hours [10]. The authors concluded that long-term DBS might have a persistent modulatory effect on the motor network. Some further impressing cases of persistent symptom relief after discontinuation of pallidal DBS in dystonia have also been reported [3, 4, 11, 12] and are summarized in Table 2.

We present a unique case of sustained benefit over years in acquired generalized dystonia after cessation of longterm chronic DBS. Our patient had sustained clinical benefit as reflected by stable improvement of the BFM scores by about 15%, which is in line with the expected benefit [13]. However, persistent improvement during 4 years after discontinuation of chronic DBS, goes beyond previous observations of prolonged benefit after DBS cessation. Effects related to neuroplasticity might have led to a mild deterioration, which was rapidly resolved by IPG replacement and restart of chronic stimulation. Similarly, as in previous reports on idiopathic or inherited dystonia our patient was under chronic DBS for several years. Our observation, however, nevertheless is remarkable since DBS is clearly less effective in acquired forms of dystonia. We posit that chronic pallidal DBS can be a genuine disease-modifying treatment in single patients with dystonia with regard to its long-term effect even after prolonged discontinuation. It remains to be elucidated, which clinical or etiologic characteristics might favour such a beneficial course.