Supplementary Table 1: Characteristics and details of studies included in the systematic review and meta-analysis, reporting tremor severity using validated (A) or non- validated tremor scales (B). Studies reporting tremor scale data References for the studies are provided in the appendix. ∗ data included in efficacy meta-analysis; ✝ data included in safety analysis of reported persistent side effect after unilateral lesioning; ‡ number of subjects with complete efficacy data (of number of subjects subjected to intervention); data on bilateral interventions in italics; n.r. not reported; - data from same cohort but different time point; retro – retrospective; pro – prospective; ? – not given;
Study n ‡ Target Lesion Guidance Desi blind Tremor Mean Mean Follow- Transient AEs (n, % of all Persistent AEs (n, %
gn Scale Score Score up, cases) of all cases)
pre post months
(mean,
range) A Studies with validated tremor
scale data
Parkinson`s Disease Tremor
RF Vim Jankovic et al. ∗ 42 V.im. (40 RF Ventriculo- retro n UPDRS 3.3±0.8 0.2±0.5 53.4 (1- # (n=62): overall 58%; mild # (n=62): overall 23%;
1995 [1] unilat., 2 graphy, CT, III rest 156) hemiparesis (12, 19%), persistant dysarthria
bilat.) macro- tremor dysarthria (12, 19%), (6, 14%), pulmonary
stimulation confusion (14, 23%), embolism (1, 2%),
contralateral ataxia (8, 13%), hypophonia (1 bilat.
dystonia (3, 5%), Vim, 50%)
hypaesthesia (2, 3%),
blepharospasm (1, 2%)
Meneses et al. ∗ 25 thalamus RF Ventriculo- retro n CRST 2.8±0.9 0.3±0.6 ? (3-18) dysarthria worsening (6, hemiparesis (1 unilat.,
1997 [2] (40 graphy, CT, hand 24%) 4%)
unilat., 5 macro- score
bilat. stimulation
staged)
∗ 25 thalamus RF MRI, macro- retro n CRST 2.4±0.8 0.2±0.4 ? (3-18) dysarthria worsening (3, none
(40 stimulation hand 12%), hemiparesis (1, 4%)
unilat., 5 score
bilat.
staged) Moriyama et ✝ 13 V.op. RF air ventriculo- retro n UPDRS 1.3 0.1 120 (6- transient hemiparesis (4, 9%), spastic hemiparesis (1, al. 1999 [3] (of (unilat.) graphy III rest 204) confusion <24h (2, 5%) 2%)
44) tremor
9 V.op. RF air ventriculo- retro n UPDRS n.r. n.r. ? (36- dysarthria (4, 44%) dysarthria (1, 11%)
(staged graphy III rest 120)
bilat.) tremor
Valalik et al. ✝ ∗ 45 V.im. / RF CT, micro- retro n UPDRS 10±1.6 0.8±1.7 6 overall (20%) facial overall (6.7%) facial
2001 [4] V.op. /macro- III tremor weakness (4, 9%), weakness (1, 2%),
(unilat.) electrode (item 21 dysequilibrium (3, 7%), limb apraxia (1, 2%),
stimulation & 22) perioral paresthesia (3, 7%), paresis (1, 2%)
limb apraxia (2, 4%),
hypotonia (2, 4%), pyrexia
(2, 4%), somnolence 2, 4%),
paresis (1, 2%), confusion (1,
2%), hemorrhage (1, 2%),
wound infection (1, 2%)
Sobstyl et al. ✝ ∗ 38 V.im. RF CT, macro- pro n UPDRS 11.2±2.1 1.8±1.1 3 overall (13, 32%); dysarthria overall (6, 15%);
2006 [5] (of (unilat.) stimulation III tremor (3, 7%), facial weakness (4, dysarthria (2, 4%),
41) (item 10%), confusion (3, 7%), facial weakness (3, 20/21, contralateral paresis (1, 2%), 7%), contralateral
OFF) paraesthesia (1, 2%) paresis (1, 2%)
RF STN
Alvarez et al. ✝ ∗ 8 (of STN RF CT, semi- pro y UPDRS 5.5±3.9 0.7±1.6 12 perioperative dyskinesia (5, severe hemi-chorea/-
2001 [6] 11) (unilat.) microelectrode III tremor 45%), postoperative ballism (1, 9%)
recording (OFF) dyskinesia (1, 9%)
Parkin et al. ✝ 8 (of STN RF MRI, retro n UPDRS 23 15 5.4 (3- worsening of speech (5, 45%) L-dopa resistant limb
2001 [7] 11) (unilat.) microelectrode III tremor 12) dystonia (3, 27%)
(OFF)
Su et al. 2002 ∗ 7 (of STN (4 RF MRI, retro n UPDRS 5.2±5.0 2.3±3.0 12 hemiballism 3-35days after hemiballism and death
[8] 8) unilat., 4 microelectrode III tremor unilat. lesion (3, 38%), due to aspiration
staged (item asymptomatic hemorrhage (1, pneumonia after
bilat.) 20/21, 12.5%) Levodopa withdrawal
OFF) (1 unilat., 25%) Su et al. 2003 ✝ ∗ 9 (of STN RF MRI, retro n UPDRS 4.8±4.8 1.6±2.3 6 hemiballism (2, 17%), hemiballism, death
[9] 13) (unilat.) microelectrode III tremor asymptomatic hemorrhage (1, from aspiration
recording (item 8%), postural asymmetry (2, pneumonia after
20/21, 17%) levodopa withdrawal
OFF) (1, 8%)
Patel et al. ✝ ∗ 16 STN RF MRI, macro- pro n UPDRS 4.6±2.3 1.4±1.4 6 - hemiballism &
2003 [10] (of (unilat.) stimulation III tremor dyskinesia (2, 8%) in
26) (OFF) both subjects only
lesioned in STN
Alvarez et al. ∗ 7 (of STN RF semi- pro y UPDRS 11.2±5.4 3.0±3.1 64 (48- subdural hematoma after fall none
2005 [11] 18) (staged microelectrode III tremor 72) (1, 5%), local scalp infection
bilat.) recording and - (OFF) (1, 5%), single epileptic
stimulation seizure (1, 5%)
∗ 11 STN RF semi- pro y UPDRS 7.0±4.7 3.3±3.6 48 (36- severe bilateral dyskinesia severe ataxia (1, 9%)
(of (simultan. microelectrode III tremor 60) within hours of lesion (3,
18) bilat.) recording and - (OFF) 15%), severe ataxia (2, 10%)
stimulation Tseng et al. ∗ 10 STN RF MRI, retro n UPDRS 14.3±11. 3.1±4.7 3 mild hemichorea (2, 20%), none
2007 [12] (staged microelectrode III tremor 3 asymptomatic thalamic
bilat.) recording & (item hematoma (1, 10%),
macro- 20/21, aspiration pneumonia (1,
stimulation OFF) 10%)
Alvarez et al. ✝ ∗ 68 STN RF CT, semi- retro n UPDRS 5.5±3.1 1.4±1.4 12 overall 22,5%; dyskinesia dyskinesia (14, 16%),
2009 [13] (of (unilat.) microelectrode III tremor (52, 58%), mild dysarthria (4, (8, 9%) of which
89) recording (OFF) 4%), wound infection (3, severe hemichorea-
3%), seizure (2, 2%), hemiballism
asymptomatic haemorrhage
(3, 3%)
RF pallidum
Iacono et al. 126 PVP (58 RF MRI, semi- retro n UPDRS 2.1 0.7 4.5 (1- overall 6.3%: hemianopsia (1, overall 3.2 %:
1995 [14] unilat., 68 microeletrode III (ON) 12) 1%), hemiparesis (1, 1%), hemianopsia (2, 3%)
bilat. recording, intracranial
simultan. macro- hematoma/abscess (3, 2%),
or staged) stimulation pallidal hematoma (1, 1%) Lozano et al. ✝ 14 Gpi RF MRI, pro y UPDRS 0.0±2.8 0.0±1.0 6 facial weakness (3, 21%), none
1995 [15] (unilat.) microelectrode III tremor euphoria (4, 29%)
recording, (OFF)
micro-
stimulation
Baron et al. ✝ ∗ 8 (of Gpi RF CT/MRI, pro n UPDRS 1.8±0.7 0.1±0.4 12 asymptomatic hemorrhage (2, dysarthria (1, 7%),
1996 [16] 15) (unilat.) microelectrode III tremor 25%), moderate dysarthria (1, superior
recording, (OFF) 12.5%), quandrantanopia (1,
micro- 7%)
stimulation
Lang et al. ✝ ∗ 39 PVP RF MRI, pro y UPDRS 2.9±2.7 1.3±1.8 6 overall: 63%; confusion (4, overall: 35%; facial
1997 [17] (of (unilat.) microelectrode III tremor 10%), facial weakness (14, weakness (2, 5%),
40) recording, (OFF) 36%), dysarthria (10, 25%), dysarthria (3, 8%),
micro- dysphagia (7, 18%), impaired dysphagia (2, 5%),
stimulation cognition (5, 13%), behaviour cognitive impairment
changes (3, 8%), (3, 8%), personality
dysequilibrium (2, 5%), changes (2, 5%),
handwriting difficulties (10, handwriting
25%), weight gain (14, 36%) difficulties (4, 10%), dysequilibrium (2,
5%),
Kopyov et al. ✝ 29 PVP RF MRI, retro y UPDRS 2.6 0.2 3 facial weakness (4, 14%) none
1997 [18] (unilat.) microelectrode III tremor
recording, (OFF)
micro-
stimulation
Ondo et al. ∗ 34 PVP RF MRI, CT, retro y UPDRS 1.8±1.6 1.1±1.1 3 confusion (4, 12%), aphasia n.r.
1998 [19] (unilat.) microelectrode III hand (1, 3%)
recording, tremor
micro-/macro- (OFF)
stimulation
Kondziolka et ✝ ∗ 58 PVP RF MRI, macro- pro n UPDRS 2.2±1.4 1.1±1.1 9 (2-24) dysarthria (4, 7%), confusion none al. 1999 [20] (unilat.) stimulation III tremor (1, 2%)
(OFF) Samii et al. 20 PVP RF CT, macro- retro n UPDRS n.r. n.r. 24 n.r. n.r.
1999 [21] (of (unilat.) stimulation III rest
24) tremor
(OFF)
Dalvi et al. ✝ ∗ 20 PVP RF CT, MRI, retro n UPDRS 4.2±2.9 2.3±1.9 3 overall (6, 30%): sleepiness overall (10, 50%):
1999 [22] (unilat.) microeletrode III rest (1, 5%), confusion (1, 5%), contralateral
recording, tremor dysphasia (1, 5%), double hemiparesis (1, 5%),
micro- (OFF) vision (1, 5%), blurred vision visual deficits (2,
stimulation (1, 5%), transient psychosis 10%), confusional
(1, 5%) episodes (3, 15%),
dyslexia (1, 5%),
weight gain (4, 20%)
Merello et al. ✝ 10 PVP RF MRI, pro, n UPDRS 6.3 2.0 12 aspiration pneumonia (1, none
1999 [23] (unilat.) ventriculo- contr III tremor 10%), seizure (1, 10%)
graphy, olled (item 20;
angiography, OFF)
microelectrode
recording,
micro- stimulation
10 best none n.a. pro, n UPDRS 5.5 5.2 12 none none
medical contr III tremor
therapy olled (item 20;
OFF)
Schrag et al. ✝ 20 ventral RF CT, micro- pro n UPDRS n.r. n.r. 12 facial weakness (2, 8%), overall (9, 41%):
1999 [24] (of medial eletrode III tremor dysphagia (3, 12%), focal quadrant anopsia (3,
26) pallidum recording, (OFF) seizures (1, 4%), postural 12%), dysarthria (5,
(unilat.) micro- instability (1, 4%), "minor 19%), abulia (1, 4%),
stimulation complications" (10, 38%) paroxysmal limb
shaking (1, 4%)
Baron et al. ∗ 10 PVP RF CT/MRI, pro n UPDRS 1.0±1.0 0.0±0.0 48 n.r. n.r.
2000 [25] (unilat.) microelectrode III tremor
recording, (OFF)
micro-
stimulation Herrera et al. ✝ ∗ 12 PVP RF Ventriculo- retro n UPDRS 4.0±2.7 1.1±1.7 16 (2- wound infection (1, 8%), dysphonia (1, 8%),
2000 [26] (unilat.) graphy, macro- III tremor 26) delirium (1, 8%) subjective visual
stimulation (OFF) impairment (1, 8%)
Molinuevo et ✝ ∗ 23 PVP RF CT, retro n UPDRS 4.3±3.0 1.7±2.2 3 dysarthria (7, 30%), facial overall (4, 17%): al. 2000 [27] (unilat.) microelectrode III tremor weakness (5, 22%), confusion dysarthria (1, 4%),
recording, (OFF) (4, 17%), dysphagia (4, 17%), facial weakness (1,
micro- depression (3, 13%), 4%), depression (1,
stimulation hypersomnia (3, 13%), 4%), quadrant anopsia
paraesthesia (1, 4%), (1, 4%), weight gain
quadrant anopsia (1, 4%), (3, 13%), decreased
weight gain (1, 4%), word fluency (4, 17%)
decreased word fluency (7,
30%)
Goto et al. ✝ ∗ 19 GPi RF MRI, retro n UPDRS 4.8±2.2 1.2±0.6 6 none none
2000 [28] (unilat.) ventriculo- III tremor
graphy, (item 20,
microelectrode 21; OFF)
recording,
macro- stimulation
Lai et al. ✝ ∗ 89 PVP RF MRI, retro n UPDRS 3.9±3.1 1.1±1.4 3 overall (7, 8%): aphasia (1, none
2000 [29] (unilat.) microelectrode III tremor 1%), hemiparesis (1, 1%),
recording, (OFF) pneumonia, confusion (1,
micro- 1%), confusion (2, 2%),
stimulation metachromatopsia (2, 2%)
Goto et al., 12 GPi RF MRI, retro N UPDRS 2.5±0.8 0.8±0.6 6 n.r. n.r.
2002 [30] (of (unilat.) ventriculo- III leg
24) graphy, tremor at
microelectrode rest (item
recording, 21; OFF)
macro-
stimulation
Vitek et al. ✝ ∗ 18 GPi RF MRI, RCT y UPDRS 0.9±1.1 0.2±0.4 6 dysarthria (1, 6%), focal none
2003 [31] (unilat.) microelectrode III tremor motor seizures (2, 12%)
recording, (OFF) macro-
stimulation
18 best none none RCT y UPDRS 1.7±1.7 1.6±1.5 6 n.r. n.r.
medical III tremor
therapy (OFF)
Sobstyl et al. ∗ 27 GPi RF CT, macro- pro n UPDRS 7.2±2.7 2.5±0.7 3 - quadrant anopsia (1,
2003 [32] (of (staged stimulation III tremor 3%), hemiparese (1,
34) bilat.) (item 3%)
20,21,
OFF)
Yen et al. ✝ ∗ 9 PVP RF MRI, macro- retro n UPDRS 3.0±2.2 1.9±2.1 24 weight gain (4, 44%), sexual none
2005 [33] (unilat.) stimulation III tremor disinhibition (1, 11%),
(OFF) auditory hallucinations (1,
11%)
Coban et al. ✝ 6 (of GPi RF MRI, RCT y UPDRS n.r. n.r. 6 homonymous hemianopsia none
2009 [34] 10) (unilat.) microelectrode III tremor (1, 17%)
recording & (OFF)
macro-
stimulation
GK V.im.
Young et al. ✝ 8 (of V.im. / GK, MRI retro y UPDRS 3.3±0.9 2.0±1.3 6 none none
1998 [35] 16) V.op. 120- III rest
(unilat.) 160Gy tremor
item 20
(ON)
Duma et a. 34 V.im. (30 GK, MRI retro n UPDRS n.r. n.r. 28 (6- n.r. n.r.
1998 [36] unilat., 4 100- III tremor 58)
bilat.) 165Gy
Young et al. ✝ ∗ 102 V.im. GK, MRI retro y UPDRS 3.6±1.1 0.8±0.6 12 mild dysequilibrium (1, 1%) mild face/limb
2000 [37] 120- III (item paresthesia (1, 1%),
160Gy 20, rest mild contralateral
tremor) paresis + dysphagia
(1, 1%)
Kooshkabadi ∗ 27 V.im. (26 GK, MRI retro n CRST 3.0±0.8 1.5±1.1 11.5 (1- # (n=86): dysphagia (1, 1%), none et al. 2013 unilat., 1 130- 152) unilateral facial hypaesthesia
[38] staged 140Gy & dysaesthesia (1, 1%)
bilat.)
Essential Tremor
RF V.im.
Goldman et ∗ 8 V.im. / RF CT/MRI, semi- retro n CRST 2.5±0.4 0.4±0.5 17.3 (1- limb hypaesthesia (2, 29%), subclinical mild al. 1992 [39] V.op. (7 microelectrode hand 50) dysarthria (2, 29%), attention dysarthria (3, 43%)
unilat., 1 recording, tremor deficit (2, 29%), anomic
bilat.) macro- dysphasia (1, 14%),
stimulation dyspraxia (1, 14%), verbal
cognitive deficit (1, 14%)
Goodman et 14 V.im. RF CT, retro n CRST n.r. n.r. 3 n.r. n.r. al. 1998 [40] (unilat.) microelectrode
recording
Pahwa et al. ✝ ∗ 17 V.im. RF n.r. retro n CRST 19.8±7.6 10.7±6.6 2.2 (1- symptomatic haemorrhage (1, none
2001 [41] (unilat.) , "motor" 27) 6%), asymptomatic
contr tremor haemorrhage (5, 29%),
olled score cognitive changes (5, 29%),
hemiparesis (2, 12%),
paresthesia (1, 6%), headache
(7, 41%), seizure (1, 6%), tremor remergence and re-
operation (2, 12%)
17 V.im. DBS n.r. retro n CRST 20.3±7.2 10.2±4.8 3.1 (1- paraesthesia (10, 59%), lead replacement (4,
(unilat.) , "motor" 27) headache (9, 53%), seizures 24%)
contr tremor (1, 6%), dizziness (2, 12%),
olled score dysequilibrium (1, 6%),
dysarthria (1, 6%)
Sobstyl et al. ✝ 9 V.im. RF CT, macro- pro n CRST 3.5 0.6 3 facial weakness (1, 11%), mild hemiparesis (1,
2006 [42] (unilat.) stimulation (item 5,6) tremor recurrence (1, 11%) 11%)
GK V.im.
Young et al. ✝ 52 V.im. GK, MRI retro y CRST 3.4 0.8 12 mild dysequilibrium (1, 2%) mild face/limb
2000 [37] 120- action paresthesia (1, 2%),
160Gy tremor mild contralateral
paresis + dysphagia
(1, 2%) Niranjan et al. ✝ ∗ 8 V.im. GK, MRI pro n CRST 3.8±0.4 0.9±0.9 6 (2-11) none none
2000 [43] (unilat.) 130- tremor
150Gy
Kondziolka et ✝ ∗ 26 V.im. GK, MRI retro n CRST 3.7±0.1 1.7±0.3 36 (4- mild hemiparesis & None al. 2008 [44] (unilat.) 130- tremor 96) dysphagia (1, 4%), mild
140Gy hemiparesis and dysarthria
(self-limiting after 18
months; 1, 4%)
Young et al. ∗ 119 V.im. GK, MRI pro n CRST 3.3±0.8 1.4±1.3 40 (±33) hypaesthesia (2, 1%), foot hypaesthesia (2, 1%),
2010 [45] (of (unilat.) 141- drawing ataxia (1, 1%), mild significant
172) 152Gy hemiparesis (3, 2%), hemiparesis +
moderate hemiparesis + dysarthria (6, 3%)
dysarthria (1, 1%)
∗ 42 V.im. GK, MRI pro n CRST 3.1±1.0 1.0±0.9 41 (±25) n.r. n.r.
(of (staged 141- drawing
172) bilat.) 152Gy
Lim t al. 2010 ✝ ∗ 11 V.im. GK, MRI pro y CRST 22.0±5.7 20.1±8.4 19.2 (7- lip/finger hypaesthesia (2, hemiparesis +
[46] (unilat.) 130- tremor 30) 14%) dysarthria (1, 7%)
140Gy sum score Kooshkabadi ✝ ∗ 48 V.im. GK, MRI retro n CRST 3.3±0.8 1.8±1.2 11.5 (1- # (n=86): dysphagia (1, 1%), none et al. 2013 (unilat.) 130- tremor 152) unilateral facial hypaesthesia
[38] 140Gy & dysaesthesia (1, 1%)
MRIgFUS
V.im.
Elias et al. ✝ ∗ 15 V.im. MRIg MRI pro n CRST 20.4±5.2 5.2±4.8 12 paresthesia (14, 93%), gait paraesthesia (4, 27%)
2013 [47] (unilat.) FUS "hand instability (5, 33%), weak
tremor grip (1, 7%), nausea (5,
subscore" 33%), sensation fo movement
(5, 33%),emesis (3, 20%)
Chang et al. ✝ ∗ 8 (of V.im. MRIg MRI pro n CRST A 5.1±1.3 1.4±1.6 6 dizziness, nausea, vomiting none
2015 [48] 11) (unilat.) FUS (5, 45%), gait instablity (1,
12.5%)
Elias et al. ∗ 56 Vim MRIg MRI RCT y CRST 18.1 ± 9.6 ± 5.1 3 dizziness, nausea (12, 21%), gait instability (9,
2016 [49] (of (unilat.) FUS "hand 4.8 paraesthesia (21, 38%), gait 16%), paraesthesia 76) tremor disturbance (20, 36%), limb (14, 25%),
subscore" dysmetria (7, 12%), hemiparesis (2, 4%)
hemiparesis (2, 4%)
✝ 56 Vim MRIg MRI RCT n - 18.1 ± 10.9 ± 12 dizziness, nausea (12, 21%), gait instability (5,
(of (unilat.) FUS 4.8 4.5 paraesthesia (21, 38%), gait 9%), paraesthesia (8,
76) disturbance (20, 36%), limb 14%), hemiparesis (1,
dysmetria (7, 12%), 2%), taste disturbance
hemiparesis (2, 4%) (2, 4%)
20 sham MRIg MRI RCT y CRST 16.0 ± 15.8 ± 3 paraesthesia (1, 5%), nausea n.r.
FUS "hand 4.4 4.9 (2, 10%)
tremor
subscore"
MRIgFUS
CTT
Gallay et al. ∗ 21 CTT (18 MRIg MRI retro n CRST 12.4±3.3 3.0±4.1 12 gait instability (3, 14%) gait instability (1, 5%)
2016 [50] unilat., 3 FUS (item 11-
staged 14, hand bilat.) tremor)
Schreglmann ∗ 6 CTT MRIg MRI pro y CRST 14.3±4.9 2.5±2.6 6 immanently reversible none et al., 2017 (unilat.) FUS (unilateral vestibular symptoms (4,
[51] hand 67%), gait instability (2,
score, 33%)
items
5,6,11-14)
Multiple Sclerosis Tremor
RF
Goldman et ✝ ∗ 5 (2 V.im. / RF CT, MRI, retro n CRST 3.5±0.5 1.2±0.8 13.3 (3- worsening of dysarthria (1, worsening of al. 1992 [52] not V.op. ventriculo- 34) 20%) dysarthria (1, 20%)
lesio (unilat.) graphy,
ned) microelectrode,
macro-
stimulation Bittar et al. ✝ ∗ 10 V.op. & RF MRI, CT, retro n Bain & 5.9±3.0 1.3±3.0 16.2 hemiparesis (2, 20%), hemiparesis (2, 20%),
2005 [53] ZI microelectrode Finley, (12-50) monoparesis (1, 10%), facial hemiparesis and
(unilat.) recording, postural palsy (1, 10%), hemiparesis seizure (1, 10%)
macro- tremor & dysarthria (1, 10%),
stimulation hemiparesis, seizure &
confusion (1, 10%)
10 V.op. & DBS MRI, CT, retro n Bain & 5.1±2.2 2.9±2.6 14.6 monoparesis (1, 10%), wound monoparesis (1,10%)
ZI microelectrode Finley, (3.1- infection (1, 10%)
(unilat.) recording, postural 23.5)
macro- tremor
stimulation
GK
Mathieu et al. ✝ ∗ 6 V.im. GK, MRI retro n CRST 4.0±0.0 1.2±0.8 25.5. (5- MS relapse 4 months after none
2007 [54] (unilat.) 130- tremor 46) intervention (1, 17%)
150Gy
Kooshkabadi ∗ 11 V.im. (10 GK, MRI retro n CRST 3.9±0.3 2.5±0.9 11.5 (1- # (n=86): dysphagia (1, 1%), none et al. 2013 unilat., 1 130- tremor 152) unilateral facial hypaesthesia
[38] staged 140Gy & dysaesthesia (1, 1%) bilat.)
Rubral tremor
RF
Goldman et ✝ ∗ 5 V.im. / RF CT, MRI, retro n CRST 3.7±0.5 0.6±0.6 3 none fatal aspiration al. 1992 [39] V.op. ventriculo- tremor pneumonia (1, 20%),
(unilat.) graphy, worsening of
microelectrode, dysarthria (1, 20%)
macro-
stimulation
Sobstyl et al. ✝ 7 V.im. RF CT, MRI pro n CRST 3.25 0.5 3 ataxia (1, 14%, tremor dysarthria (1, 14%)
2004 [55] (unilat.) (item 5,6) recurrence (1, 14%))
B Studies without validated tremor
scale data
Parkinson`s Disease Tremor
Leukotome
V.im.
Atkinson et 25 V.im. leukot MRI, retro n n.r. n.r. n.r. 2 n.r. n.r. al. 2002 [56] ome ventriculo-
graphy, macro-
stimulation
Leukotome, pallidum
Jimenez et al. ✝ 9 GPi leukot CT, macro- RCT n New York n.r. n.r. 6 contralateral leg paresis (1, none
2006 [57] (unilat.) ome stimulation Parkinson 10%), hypophonia (1, 10%)
´s disease
scale,
tremor
(OFF) 9 GPi DBS CT, macro- RCT n New York n.r. n.r. 6 oral dyskinesia (?, ?) none
(unilat.) stimulation Parkinson
´s disease
scale,
tremor
(OFF)
RF V.im.
Wester et al. 33 V.oa. / RF gas- retro n clinical n.r. n.r. 24 (3- confusion (4, 8%), cognitive (3, 6%),
1990 [58] (of V.op. (47 encephalograph 89) hemiparesis (3, 6%), dysphasia (1, 2%),
48) unilat., 1 y, macro- dysphasia (4, 8%), dysarthria dysarthria (2, 4%)
staged stimulation (1, 2%)
bilat.)
Fox et al. 36 V.im. (35 RF CT, ventriculo- retro n clinical n.r. n.r. 3 overall (22, 61%): facial overall (5, 14%);
1991 [59] unilat., 2 graphy, semi- weakness (10, 28%), tremor recurrence (2,
staged microelectrode cognitive symptoms (5, 6%), arm dyspraxia (2,
bilat.) 14%), dysarthria (5, 14%), 6%) dysarthria (3,
arm/hand paresis (5, 14%), 8%), dysphasia (1,
dyspraxia (3, 8%), 3%), abulia (1, 3%) hypaesthesia (2, 5%)
Quiñones- ✝ 11 V.im. RF CT, retro n clinical n.r. n.r. 4.5 (3-6) overall (8, 73%): hypotonia, none
Molina et al. (unilat.) microelectrode hemiparesis, speech
1994 [60] recording, disturbance (5, 45%),
macro- changed proprioception,
stimulation ataxia (3, 27%)
Brophy et al. 25 thalamus RF CT, MRI, retro n clinical n.r. n.r. 36 (11- hemineglect (2, 8%), gait hemineglect (2, 8%),
1997 [61] (23 ventriculo- 96) disturbance due to gait disturbance due to
unilat., 2 graphy, macro- proprioceptive ataxia (1, 4%), proprioceptive ataxia
bilat.) stimulation (1, 4%),
Tasker et al. ✝ 23 V.im. RF CT, retro n clinical n.r. n.r. 27 (3- overall (9, 35%): tremor overall (13, 50%):
1998 [62] (of microelectrode >60) recurrence (1, 4% ); dysarthria (1, 4%),
26) recording, intracerebral hematoma (1, hand ataxia (4, 15%),
macro- 4%), confusion (1, 4%), gait disturbance (3,
stimulation parkinsonian crisis (2, 8%), 12%), paraesthesia (5,
dysarthria (2, 8%), gait 19%), disturbance (1, 4%)
paraesthesia (4%)
16 V.im. DBS CT, retro n clinical n.r. n.r. 10 (3- tremor recurrence (1 ,5%), dysarthria (1, 5%),
(of microelectrode >36) confusion (1, 5%), gait disturbance (1,
19) recording, parkinsonian crisis (1, 5%), 5%),
macro- dysarthria (1, 5%), hand
stimulation ataxia (1, 5%), gait
disturbance (1, 5%),
paraesthesia (9 , 47%),
nausea (1, 5%), implant local
swelling (3, 16%), electrode
issues (3, 16%)
Giller et al. ✝ 31 V.im. RF CT, MRI, retro n clinical n.r. n.r. 5.2 hemiparesis, dysarthria (6, dysequilibrium (1,
1998 [63] macro- 19%), wound infection, 3%)
stimulation dysequilibrium (1, 3%) Linhares et al. 38 V.im. (34 RF Ventriculo- retro n non- n.r. n.r. 35.8 (1- paresthesia (16, 42%), ataxia ataxia (5, 13%), gait
2000 [64] unilat., 4 graphy, CT, validated 152) (9, 24%), difficulties (3, 8%),
bilat.) MRI, scale
microelectrode
recording
RF STN
Merello et al. 5 (of STN RF MRI, RCT n UPDRS 50.6 24.2 12 dysequilibrium with falls (1, severe left
2009 [65] 16) (bilat.) microelectrode III (off), 20%) hemiballism (1, 20%)
recording & no tremor
macro- data
stimulation
5 (of STN unilat. MRI, RCT n UPDRS 54 20.6 12 hemiballism (1, 20%), none
16) (bilat.) RF + microelectrode III (off), electrode externalization (1,
contral recording & no tremor 20%), seizure (1, 20%)
at. macro- data
DBS stimulation 6 (of STN DBS MRI, RCT n UPDRS 46 18 12 irritability, insomina, postoperative death (1,
16) (bilat.) microelectrode III (off), agitation (2, 33%), apathy (1, 17%)
recording & no tremor 17%)
macro- data
stimulation
RF pallidum
Laitinen et al. 32 PVP (34 RF CT, macro- retro n clinical n.r. n.r. 28 (2- facial weakness & dysphasia visual field deficit (6,
1992 [66] (of unilat., 4 stimulation 71) (1, 3%) 16%)
38) bilat.)
Dogali et al ✝ 18 PVP RF MRI/CT, pro, y UPDRS, n.r. n.r. 12 sexual disinhibition for 24h none
1995 [67] (unilat.) microelectrode contr no tremor (1, 6%)
recording, olled data
macro-
stimulation Shima et al. 86 PVP (58 RF MRI, retro n clinical, n.r. n.r. 8 (3-30) bulbar signs (3, 3%), paresis after bilat. surgery:
1996 [68] unilat., 18 ventriculo- no tremor (1, 1%) hemiparesis (1, 4%),
simultan., graphy, data motor aphasia (1,
10 staged microelectrode 4%), dysarthria &
bilat.) recording, hypersalivation (3,
macro- 11%)
stimulation
Taha et al. 44 PVP (25 RF MRI, retro n patient 2.3 1.5 6 (3-9) n.r. n.r.
1997 [69] unilat., 19 microelectrode subjective
simultan., recording VAS
bilat.) tremor
score
Johansson et 20 PVP RF CT/MRI, pro n UPDRS 25 10 4 n.r. n.r. al. 1997 [70] (of (unilat.) microelectrode III rest
22) recording, tremor
micro- VAS
stimulation Giller et al. 55 GPi (48 RF CT, MRI, retro n no data on n.r. n.r. 12 n.r. dysarthria (8 of all 55
1998 [63] unilat., 4 macro- tremor GPi lesions, 14.5%; 1
staged stimulation response of 48 unilat. Gpi
bilat., 3 in GPi lesion, 2%; 3 of 7
simultan. group bilat. GPi lesion,
bilat.) 43%; )
Eskandar et ✝ 25 PVP RF MRI, CT, retro n non- 1.3 0.6 24 mild hemiparesis (4, 5%), homonymous al. 2000 [71] (of (unilat.) macroelectrode validated single generalized seizure (2, hemianopsia (1, 1%)
75) recording, scale 3%), asymptomatic cortical
macro- hemorrhage (2, 3%),
stimulation confusion (2, 3%), dysarthria
(1, 1%),
Favre et al. 22 pallidum RF MRI, retro n self n.r. n.r. 7 (3-36) n.r. n.r.
2000 [72] (of (unilat.) microelectrode assessmen
56) recording, t (VAS)
macro-
stimulation
17 pallidum RF MRI, retro n self n.r. n.r. 7 (3-36) n.r. n.r.
(of (simultan. microelectrode assessmen 56) bilat.) recording, t (VAS)
macro-
stimulation
Landy et al. 21 ventral RF MRI, macro- retro n UPDRS n.r. n.r. ? (1-12) facial weakness (3, 14%), n.r.
2000 [73] medial stimulation (OFF), no hemiparesis (1, 5%)
pallidum tremor
(unilat.) data van Horn et 25 PVP RF MRI, pro n no tremor n.r. n.r. 12 n.r. n.r. al. 2001 [74] (of (unilat.) microelectrode data
32) recording,
macro-
stimulation
Blomstedt et ✝ 5 PVP RF MRI, macro- retro n/y UPDRS n.r. n.r. 37 (22- none none al. 2006 [75] (unilat.) stimulation no tremor 60)
data
Balas et al. ✝ 18 GPi RF MRI, semi- pro n UPDRS n.r. n.r. 6 none none
2006 [76] (of (unilat.) microelectrode III, no
28) recording, tremor
macro- data stimulation
GK V.im.
Pan et al. ✝ 6 (of V.im. / GK, MRI retro n clinical n.r. n.r. 4.5 (2-9) monoparesis (1, 12.5%), none
1996 [77] 8) V.oa. / 160-
V.op. 180Gy
(unilat.)
MRIgFUS
V.im.
Schlesinger et ✝ 7 V.im. MRIg MRI retro n UPDRS 2.7±1.1 0.0±0.0 0.25 gait instability (2, 28%) hypogeusia (1, 14%) al. 2015 [78] (unilat.) FUS (item 20, (eff.),
rest 8 ± 4.1
tremor) (safety)
Magara et al. ✝ 13 PTT MRIg MRI retro n UPDRS 18.7 10.2 3 none none
2014 [79] (unilat.) FUS III sum
Essential Tremor
RF V.im.
Jankovic et al. ✝ 6 V.im. RF Ventriculo- retro n non- n.r. n.r. 59.2 (1- none mild hemiparesis (1,
1995 [1] (unilat.) graphy, CT, validated 156) 17%)
macro- tremor
stimulation scale
Shahzadi et 22 V.im. (19 RF macro-/micro- retro n clinical/no 3.6 1.5 ? (3- hematoma (1, 5%), confusion hemiparesis (1, 5%), al. 1995 [80] unilat., 3 stimulation n- >60) (1, 5%), dysarthria (1, 5%), dysarthria (1, 5%),
bilat.) validated hypaesthesia (3, 14%), gait disturbance (1,
seizure (2, 10%), wound 5%), hypaesthesia (2,
infection (1, 5%) 10%)
Zirh et al. 21 V.im. (18 RF MRI, pro n clinical 3.0 0.9 12 dysarthria (1, 5%) perioral numbness (1,
1999 [81] unilat., 3 microelectrode (postural 5%), mild
staged recording tremor dysequilibrium (1,
bilat.) amplitude 5%), mild dysarthria
) (2 of the 3 bilat.
patients, 66%) Akbostanci et 37 V.im. (36 RF MRI, CT, retro n n.r. n.r. n.r. ? (1-13) tremor recurrence (5, 14%), hemiparesis & speech al. 1999 [82] unilat., 1 ventriculo- speech & motor function (15, difficulties (6, 16%)
staged graphy, macro- 41%)
bilat.) stimulation
GK V.im.
Young et al. ✝ 8 V.im. / GK, MRI retro n clinical n.r. n.r. 22.3 none none
1998 [35] V.op. 120- (11-50)
(unilat.) 160Gy
Multiple Sclerosis Tremor
RF
Wester et al. ✝ 9 V.oa. / RF Gasencephalo- retro n clinical n.r. n.r. 24 (3- confusion (2, 22%), overall (9, 100%):
1990 [58] V.op. graphy, macro- 89) hemiparesis (2, 22%), cognitive (1, 11%),
stimulation dysphasia (1, 11%) hemiparesis (3, 33%),
dysphasia (2, 22%),
dysarthria (2, 22%) Whittle et al. ✝ 9 V.oa. / RF CT, MRI, retro n clinical n.r. n.r. 3 (1-12) psychomotor slowing, profound depression
1995 [83] V.op. / macro- confusion (5, 56%), urinary (2, 22%)
V.im. stimulation dysfunction (2, 22)
(unilat.)
Shahzadi et ✝ 46 V.im. RF macro-/micro- retro n clinical 4.5 1.8 ? (3- subdural hematoma (1, 2%), overall (17, 37%): MS al. 1995 [80] (unilat.) stimulation 120) confusion (3, 7%), worsening (4, 9%),
hemiparesis (10, 22%), facial cognitive disturbance
weakness (1, 2%), dysarthria (2, 4%), hemiparesis
(8, 17%), ataxia (2, 4%), gait (4, 9%), dysarthria (2,
disturbance (1, 2%), 4%), ataxia (2, 4%),
meningitis (1, 2%) gait disturbance (1,
2%), hypaesthesia (2,
4%)
Critchley et 24 V.im. (21 RF CT, MRI, retro n clinical 2.8 1.8 30 (?-?) postoperative fatigue (7, hemiparesis (1, 8%), al. 1998 [84] unilat., 3 macro- 29%), confusion (2, 8%), dysarthria (1, 8%)
staged stimulation postoperative seizur (2, 8%),
bilat.) postoperative MS relapse (2,
8%), transient hemiparesis (1,
4%) Hassan et al. ✝ 6 V.im. RF MRI, retro n MS 61.7±11. 55.3±17. 12 none none
2012 [85] (unilat.) microelectrode tremor 0 4
recording disability
scale
Rubral tremor
RF
Krauss et al. 29 12 ZI RF CT, ventriculo- retro n tremor 56.9±14. 36.5±18. 126 (6- dysarthria (10, 29%), dysarthria (11, 34%),
1994 [86] (of (unilat.), graphy, macro- disability 5 0 276) dysphagia (2, 6%), mild truncal ataxia (3, 9%),
35) 25 ZI / stimulation (CRST) hemiparesis (9, 26%), facial hemiballism (2, 6%)
V.oa. / hemiparesis (5, 14%), truncal
V.op. (23 ataxia (5, 14%), confusion (8,
unilat., 2 23%)
staged
bilat.), 2
medial
pulvinar Shahzadi et ✝ 25 V.im. RF macro-/micro- retro n clinical 3.9 1.8 ? (3-60) subdural hematoma (1, 4%), hemiparesis (4, 16%),
al. 1995 [80] (unilat.) stimulation confusion (2, 8%), dysarthria hypaesthesia (3, 12%)
(4, 16%), ataxia (1, 4%),
hypaesthesia (2, 8%), seizure
(2, 8%)
Jankovic et al. ✝ 6 V.im. RF Ventriculo- retro n clinical n.r. n.r. 47.2 (1- - ataxia (1, 17%),
1995 [1] (unilat.) graphy, CT, 156) dysarthria (1, 17%),
macro- paresis (1, 17%)
stimulation
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