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Figure 1: Anatomical Location of the Caudal Zona and z=-2.1±1mm.
This target is posterolateral to that defined by other
groups who have stimulated the subthalamic region
Figure 2C in Plaha et al., 2008
In five patients with tremor-dominant PD, resting tremor improved by a
significant 94.8% and postural tremor by 88.2%. In six patients with
distal essential tremor, the total tremor score improved by 75.9% (part
A of the tremor rating scale by 85.6%, part B by 63.3% and part C by
84.5%). Four patients with proximal MS tremor showed a 57.2%
improvement in the total tremor rating score (part A 83.1%, part B
55.6% and part C 36.1%). In the single patient with Holmes tremor,
there was a 70.2% improvement in the total tremor score. Proximal
cerebellar tremor (CT) in one patient improved by 60.4% (part A 66.7%,
part B 60.6% and part C 62.5%). In the single patient with dystonic
tremor there was improvement in both the dystonia and the tremor
(Burke Fahn Marsden dystonia movement score 65.1% improvement;
disability score 61.5% and a 70.5% improvement in the tremor score). A: Intraoperative axial magnetic resonance imaging scan with bilateral stylettes in the caudal
zona incerta; B: Matching slice from the Schaltenbrand atlas, with the red dot defining the
target location in the caudal zona incerta.
Bilateral cZI stimulation was very effective in completely suppressing
Large lesions involving the ZI and the surrounding white matter tracts, head and neck tremor in three ET patients and one MS tremor patient
including the prelemniscal radiation, were shown to be effective in along with improvement in truncal ataxia and cerebellar speech. Since
suppressing distal tremor with a resting, postural or kinetic component the recently published data, six more patients have undergone bilateral
in patients with PD
In 1969, Bertrand and colleagues
defined cZI stimulation for MS and ET. Although as yet unpublished, the
an area where the mere impact of the tip of a small probe caused abrupt improvement seen in all components of tremor has been similar to the
and total cessation of tremor. This area was in the region of the published data,
further cementing this nucleus as an effective target
‘prelemniscal radiation’. Bertrand and colleagues attributed their for all forms of tremor. We have seen that high-frequency stimulation
findings to lesioning the ascending fibres from the upper mesencephalic (mean 140Hz) is most effective in suppressing tremor at low voltages,
reticular substance, the pallidothalamic and pallidotegmental fibres. We although a couple of patients with MS tremor have benefited from low-
now know that this area also carries the dentate- and interpositus- frequency (40Hz) stimulation at a pulse width around 210µseconds. In
thalamic fibres on the way to the Vim. This white matter prelemniscal our published series and recently operated patients there were no peri-
radiation has been stimulated unilaterally to alleviate resting tremor in operative complications, especially intra-operative haemorrhage. One
and distal postural and kinetic tremor in ET (performed patient developed transient dysphagia secondary to an error in frame
Unilateral stimulation encompassing both the rZI and relocation with implantation of both DBS leads into the VL nucleus of
prelemniscal radiation has been shown to be very effective in thalamus. Transient peri-DBS-lead-related oedema in the prelemniscal
suppressing distal PD tremor,
and proximal limb tremor radiation caused dyseqilibrium in two patients. The DBS lead and
as in ET,
and cerebellar (CT),
and multiple sclerosis generator were removed in one patient due to infection. Most
More recently, some centres have targeted the STN to importantly, all patients maintained constant bilateral stimulation
improve non-parkinsonian dystonic tremor
although the to suppress their tremor and no patient developed tolerance to
active stimulation contact has been in the subthalamic region stimulation as is commonly seen with VL nucleus stimulation.
encompassing the rZI and the prelemniscal radiation. Most groups, as
discussed above, have performed unilateral stimulation of the posterior Tremor and Zona Incerta
subthalamic region encompassing the prelemniscal radiation and the The cZI nucleus as discussed above is a very effective target to
The DBS lead has been implanted contralateral to the worst suppress all forms of tremor affecting the proximal and distal body part.
affected side. This region has a high concentration of ascending dentato- The mechanisms underlying the generation of tremor remain poorly
cerebello-rubro-thalamic fibres to the Vim nucleus, and when bilateral understood and, despite a number of hypotheses, there remain
stimulation has been attempted, patients have developed disequilibrium significant gaps in our understanding of it. In none of the proposed
and dysarthria as seen following bilateral Vim nucleus stimulation.
We hypotheses does the cZI nucleus play a role in either the generation or
noted a 40% incidence of the above complication following implantation conduction of tremor oscillations and yet in recent publications we
of a bilateral DBS lead medial to the STN in patients with PD.
have demonstrated that high-frequency stimulation of this region has a
potent antitremor effect.
We present our current understanding of
Caudal Zona Incerta Nucleus the anatomy and physiology of the cZI and then discuss its proposed
Over the past few years we have been performing magnetic role in the pathophysiology of PD and non-PD tremor. We also discuss
resonance imaging (MRI)-guided bilateral stimulation of the cZI nucleus how and why high-frequency stimulation of the cZI suppresses tremor.
using the implantable guide tube technique for both parkinsonian and
In our recent publication on 18 patients Zona Incerta Nucleus and Its Function
(five PD tremor and 13 non-PD tremor) with tremor affecting both The ZI, an embryological derivative of the ventral thalamus, is a distinct
the proximal and distal body parts (Holmes, cerebellar, ET, MS and heterogenous nucleus that lies at the base of the dorsal thalamus.
dystonic tremor), we defined the optimal target posteromedial to divided into four sectors (rostral, dorsal, ventral and caudal). The rostral
the posterodorsal STN. The co-ordinates with reference to the component extends over the dorsal and medial surface of the STN while
anterior–posterior commissure were x=14.2±1.56mm, y=-5.7±1.32mm its caudal or motor component lies posteromedial to the STN.
92 EUROPEAN NEUROLOGICAL REVIEW