Deep brain stimulation for the treatment of uncommon tremor syndromes

Figures & data

Figure 1. LEFT. T1 Weighted Axial Magnetic Resonance image showing multi-target DBS with bilateral thalamic (VIM and VoP) leads along with ipsilateral Gpi DBS (red dot). RIGHT. Upper midbrain anatomical axial image showing the relevant Posterior Subthalamic area DBS anatomy and neurosurgical target (Red X). Red Nucleus (Ru), Subthalamic nucleus (STN), Caudal zona Incerta (cZi), medial lemniscus (Lm). Full color available online

Table 1. Case reports and series of thalamic and subthlamic deep brain stimulation in patients with Holmes tremor.

Author	Number of patients and etiology	Target	Outcome	Follow-up
Pahwa et al. (2002) [27]	Midbrain cavernous hemangioma (symptoms for 3 years)	Right VIM	Significant improvement in postural and resting tremor; kinetic component persisted.	10 months
Romanelli et al. (2003) [28]	Unknown, severe symptoms 6 years	Left VIM and left STN	Tremor component improved 66%.	2 years
Samadani et al. (2003) [29]	Left midbrain cavernous malformation (symptoms for 4 years)	Contralateral VIM	57% increase in dexterity and four-point decrease in functional disability in TRS.	N/A
Nikkhah et al. (2004) [30]	1.Right infarct midbrain (tremor symptoms 6 months); 2. Left thalamic AVM	Two patients with contralateral VIM	Almost complete tremor resolution (80% improvement). Dystonia and rigidity benefit reported	7 months and 6 months, respectively
Piette et al. (2004) [31]	Pontine tegmental hemorrhage	Right VIM	Major functional improvement	16 months
Foote et al. (2006) [2]	Posttraumatic tremors Three patients with symptoms for 16 years, 3 years, and 4 years	Two patients with VIM (border VIM/VOP and one with border VOA/VOP)	Total TRS improvement of 38.46 %, 48.33%, and 66.67 %, respectively	12 months, 6 months, and 8 months, respectively
Bandt et al. (2008) [32]	Left midbrain cerebral infarction (symptoms for 7 months)	Left lenticular fasciculus	Almost complete resolution of postural and intention tremors; scored 1/4 on the WHIGET	16 months
Diederich et al. (2008) [33]	1. L venous pontine angioma (symptoms for 7 years) 2. R midbrain hemiatrophy (symptoms for 32 years)	Two patients with contralateral VIM	Substantially ameliorated postural > rest > intention component	7 years and 5 years, respectively
Peker et al. (2008) [34]	Left thalamic abscess (symptoms 18 months)	Right VIM	90% overall improvement	2.5 years
Plaha et al. (2008) [35]	No obvious MRI abnormality (symptoms for 6 years)	Contralateral caudal Zi	70.2% improvement in total TRS	N/A
Acar et al. (2010) [36]	Subarachnoid hemorrhage (symptoms less than 1 month)	Bilateral VIM	No tremor and reduction in disability due to tremor	3 months
Castrop et al. (2013) [37]	1.Hypertensive mesencephalic hemorrhage (symptoms for 1 year) 2.pontomesencephalic AVM hemorrhage (symptoms for 2 years)	Two patients with contralateral VIM	Good tremor suppression, whereas the other symptoms remained unchanged	7 years and 6 years, respectively
Issar et al. (2013) [38]	One patient with posttraumatic tremor (symptoms for 6 months) with associated dystonia and cerebellar and cognitive difficulties.	Bilateral VIM	Partial benefit (CGI scale 3). No TRS available. Dystonia persisted	N/A
Follett et al. (2014) [39]	Posttraumatic HT (symptoms for 15 years)	Bilateral VIM	Reduction of tremor from a score of 3 to a score of 1 in the right arm and from 3.5 to 0 in the left arm (TETRAS scale)	12 months
Grabska et al. (2014) [40]	Ischemic left thalamic stroke (symptoms 30 years)	Contralateral Voa and Zi	TRS 73% reduction in tremor	4 years
Kobayashi et al. (2014) [41]	1. Brainstem thalamus hemorrhage (symptoms for 6 years) 2. Cerebral infarction (symptoms for 3 years) 3. Intracerebral midbrain hemorrhage (symptoms 8 months 4. Posttraumatic (symptoms for 2 years)	Four patients with dual-lead stimulation of ventralis oralis/ventralis intermedius nuclei (VO/VIM) and PSA	87% mean improvement in tremor	25 months
Kilbane et al. (2015) [18]	1. Right brainstem hemorrhage due to cavernous malformation 2.Multicystic brainstem tegmentum lesions 3.Left thalamic midbrain bullet fragment 4.Right thalamic/subthalamic infarction	Patient 1 had VIM/Voa and Gpi leads. Patient 2 and 4 had unilateral Gpi. Patient 3 had VIM/Gpi leads	TRS improved from a mean 53.25 points prior to surgery to 11.25% representing a 78.87% benefit	Mean length of follow-up: 33.7 months.
Espinoza-Martinez et al. (2015) [42]	Two patients with ICH due to cavernous malformations, four patients with cerebral infarction, two patients with ICH, and two patients with MS.	Six patients with unilateral Gpi, one patient with bilateral Gpi, one patient with bilateral VIM, and two patients with unilateral VIM	64% mean modified TRS improvement	Mean length of follow-up: 5.8 years

GPi, globus pallidus internus; ICH, intracranial hemorrhage; PSA, posterior subthalamic area; RS, tremor rating scale; STN, subthalamic nucleus; TETRAS, The Essential Tremor Rating Assessment Scale; TVIM, ventral intermedius nucleus; Voa, ventralis oralis anterior nuclei; WHIGET, Washington Heights-Inwood Genetic Study of Essential Tremor; Zi, zona incerta.

Table 2. Case reports and series of thalamic and subthalamic deep brain stimulation (DBS) in patients with dystonic tremor..

Author	Etiology	Target	Outcome	Follow-up
Minguez-Castellanos et al. (1999) [51]	One patient with PWT	Contralateral VIM	Clinical improvement in TRS of 4 points	1 year
Kitagawa et al. (2000) [52]	One patient with DT	Contralateral VIM	Tremor markedly improved. Speech was improved as well	N/A
Racette et al. (2001) [53]	One patient with PWT	Contralateral VIM	Marked improvement in TRS from 18/144 to 1/144 (94% improvement)	N/A
Vercueil et al. (2001) [54]	Four patients with dystonic arm tremor	Contralateral VLp	Improvement in tremor with VLP DBS despite no benefit in dystonia	12 months
Deuschl et al. (2002) [55]	One patient with DT	Bilateral VIM	Tremor improvement (no specific scale or percentage reported)	N/A
Krause et al. (2004) [56]	One patient with severe dystonic cervical tremor in a series of patients with primary dystonia	Bilateral Gpi	55.6% mean improvement in BFMDS motor score in cohort, no improvement in dystonic cervical tremor	36 months
Chou et al. (2005) [57]	Severe cervical tremor	Bilateral STN	TWSTRS improved from 14 to 3 points	Six months
Fukaya et al. (2007) [58]	5 patients with PWT	Contralateral VIM (4) and Gpi (1)	91% mean improvement in BMFDR handwriting scale	24 months
Schadt et al. (2007) [59]	One patient with head dystonic tremor	VIM + Gpi	Patient reported dramatic improvement in quality of life	N/A
Plaha et al. (2008) [35]	DT in setting of generalized dystonia	Caudal Zi	65% and 70% improvement in BFM and TRS, respectively	12 months
Blomstedt et al. (2009) [60]	Two patients with DT and one patient with PWT	Contralateral PSA	Patients with DT had resolution of tremor and 80% benefit in PWT	12 months
Jeong et al. (2009) [61]	One patient with postanoxic generalized dystonia with asymmetric DT	Bilateral PSA	There was 80.5% and 89.5% improvement on the movement scale and the disability scale of the BFMDRS, respectively, and 64.9% improvement in TRS	6 months
Kuncel et al. (2009) [62]	One patient with DT in myoclonus-dystonia	Bilateral VIM	Marked tremor improvement using CGI scale and >50% improvement in TRS	9 months
Woehrle et al. (2009) [63]	Two patients with prominent DT	Contralateral VIM DBS	53.6% and 59.8% improvements in motor	11–21 months
Torres et al. (2010) [64]	One patient with dystonic neck tremor and CD, right torticollis	Right Gpi	75% reduction in dystonic tremor and 60% in cervical tremor (TWSTRS)	3 months
Morishita et al. (2010) [65]	One patient with DT and generalized dystonia, one patient isolated DT, one patient with DT and segmental dystonia	One patient with unilateral and bilateral VIM and one patient with bilateral VIM + Gpi	50% improvement in TRS in two patients and 25% in one patient	4 years in two patients and 6 months in one patient
Lyons et al. (2011) [66]	One patient with PWT	Contralateral VIM	No scales reported. Complete resolution of writing tremor	Six months
Hedera et al. (2013) [67]	Six patients generalized dystonia; three patients hemidystonia, one segmental dystonia	Four patients received VIM; six patients bilateral Gpi; two patients combined VIM + Gpi	Average benefit in WHIGET scores was 84.7% with VIM vs. 39.8% with Gpi	N/A

BMFDRS, Burke–Marsden–Fahn’s Dystonia Rating Scale; CD, cervical dystonia; DT, dystonic tremor; FTM, Fahn–Tolosa–Marin Tremor Rating Scale; GPi, globus pallidus internus; PWT, primary writing tremor; STN, subthalamic nucleus; VIM, ventral intermedius nucleus; VLp, ventrolateral posterior thalamus; WHIGET, Washington Heights-Inwood Genetic Study of Essential Tremor; Zi, Zona incerta.

Table 3. Case reports and series of thalamic and subthalamic deep brain stimulation (DBS) in patients with cerebellar tremor.

Author	Etiology	Target	Outcome	Follow-up
Freund et al. (2007) [73]	One patient with SCA-2	Bilateral Combined dual target Vop/VIM and Zi	Resolution of postural, head, chin, or voice tremor; some residual intention tremor noted at 6 months	2 years
Plaha et al. (2008) [35]	One patient with CT	Bilateral PSA	60% improvement in total TRS	N/A
Blomstedt et al. (2009) [60]	One patient with CT	Unilateral PSA	87% benefit in TRS	12 months
Ferrara et al. (2009) [74]	One patient with FXTAS	Bilateral VIM	56% improvement in TRS; deterioration of speech and gait overtime were reported	21 months
Senova et al. (2012) [69]	One patient with FXTAS	Unilateral VIM	73.4% improvement in TRS	6 months
Xie et al. (2012) [75]	One patient with FXTAS	Unilateral VIM	Tremor improvement requiring increases of stimulation over time	24 months
Mehanna et al. (2014) [76]	One patient with FXTAS	Staged Bilateral VIM	Tremor improvement with unilateral surgery. Ataxia worsened after bilateral DBS despite improvement in tremor	6 months
Oyama et al. (2014) [77]	SCA-2 FXTAS Ataxia NOS SCA 17	Contralateral VIM or unilateral Vop/VIM + Vop/Voa	50% improvement in TRS, but worsening gait and limb ataxia reported	6 months to 12 months
Oyama et al. (2014) [78]	FXTAS	Unilateral PSA	57.6% improvement in TRS	6 months
Weiss et al. (2014) [79]	3 patients with FXTAS	two patients with bilateral VIM and one patient with bilateral VIM/border zone of PSA	Sustained mean improvement of 70% in TRS	4 years in 2 patient and 2 years in one patient
Dos Santos Ghilardi et al. (2015) [80]	FXTAS	Bilateral Vop thalamic nucleus and Zi (VoP/ZI)	Improvement of 55% in TRS	33 months

FXTAS, fragile X-associated tremor/ataxia syndrome; PSA, posterior subthalamic area; TRS, tremor rating scale; Voa, ventralis oralis anterior nucleus; VIM, ventral intermedius nucleus; Vop, ventralis oralis posterior nucleus; Zi, zona incerta.

Table 4. Case reports and series of thalamic and subthlamic deep brain stimulation (DBS) in patients with posttraumatic tremor.

Author	Target	Outcome	Follow-up
Broggi et al. (1993) [96]	Unilateral VIM DBS	Improved function without tremor	10 months
Hooper et al. (2001) [97]	Unilateral junction of ZI and subthalamic region DBS	Long term abolition of the movement disorder after lesioning effect	44 months
Umemura et al. (2004) [98]	Unilateral VIM DBS	52% increase in functional speed in timed task performance trials, and increased independence in activities of daily living	12 months
Green et al. (2005)	DBS of right ZI and VOP (ipsilateral)	Increased functional use of left arm	2 years
Broggi et al. (2006) [99]	Three patients treated with ZI and VOA/VOP DBS	Marked benefit with all patients regained autonomous self-feeding	12–36 months
Foote et al. (2006) [2]	Three patients treated with ipsilateral, dual VIM, and VOA/VOP lead DBS	38–67% reduction in TRS scores	12 months, 6 months, and 8 months, respectively
Franzini et al. (2011) [100]	Nine patients; six unilateral, three bilateral VIM DBS	>50% tremor reduction in all cases	12 months
Issar et al. (2013) [38]	Three patients managed with unilateral VIM, one patient with bilateral VIM and One patient with bilateral Gpi	Percentage change in TRS scores was available for three patients and ranged from 14.3% to 56.5%	Mean follow-up 2 years
Reese et al. (2011) [101]	Unilateral VIM + STN	Reduction in UPDRS III score and TRS score from 25 and 8 to 8 and zero, respectively	5 years
Follett et al. (2014) [39]	Bilateral VIM	Tremor reduction from a score of 3 to a score of 1 in the right arm and from 3.5 to 0 in the left arm (TETRAS scale)	18 months

GPi, globus pallidus internus; STN, subthalamic nucleus; TETRAS, The Essential Tremor Rating Assessment Scale; TRS, tremor rating scale; VIM, ventral intermedius nucleus; Voa, ventralis oralis anterior nucleus; Vop, ventralis oralis posterior nucleus; Zi, zona incerta.

Table 5. Case reports and series of thalamic deep brain stimulation (DBS) in patients with orthostatic tremor (OT).

Author	Target	Outcome	Follow-up
Espay et al. (2008) [105]	Two patients with bilateral VIM and unilateral (right) DBS	Marked clinical improvement in patient with bilateral procedure. Patient with unilateral DBS noted tremor recurrence at 3 months	18 months
Guridi et al. (2008) [103]	One patient with bilateral VIM DBS	Marked cessation of tremor bilaterally	4 years
Magarinos-Ascone et al. (2010) [106]	One patient with bilateral VIM DBS	The patient could stand normally without any help or leg tremor	12 months
Yaltho et al. (2010) [107]	One patient with bilateral VIM DBS	Marked improvement in both his OT and hand tremor, ability to stand improve from 35 s to 4 min	6 months
Lyons et al. (2012) [108]	One patient with bilateral VIM DBS	Subjective improvement of 80% in OT in left leg and 50% improvement in right leg. Patient was able to stand in place for 7 min before needing to sit	30 months
Contarino, et al. (2015) [109]	One patient with bilateral VIM DBS	Marked symptomatic improvement which gradually decreased over time	5 years
Hassan et al. (2016) [110]	Two patients with bilateral VIM DBS	Good response immediately postoperatively, improved standing ability and reduction of OT severity	3 years
Coleman et al. (2016) [111]	Two patients with bilateral VIM DBS	Improvement in standing time patient 1: 50 s at baseline to 15 min and patient 2: 34 s at baseline to 4.2 min	16 months and 7 months, respectively

VIM, ventral intermedius nucleus.

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