Keywords
essential tremor - DBS under general anesthesia - caudal zona incerta (cZI) - pyramidal
tract side effects
Introduction
Deep brain stimulation (DBS) of caudal zona incerta (cZI) is an effective treatment
for medication-refractory essential tremor (ET), especially when traditional targets
like the ventral intermediate nucleus (VIM) are not effective. Recent studies suggest
that targeting subthalamic nucleus (STN), globus pallidus interna (GPi), and/or cZI
may provide better outcomes for patients with prominent postural and action tremors.[1] However, DBS surgery for ET under general anesthesia (GA) presents challenges, as
patient feedback—crucial for identifying side effects like pyramidal tract side effects
(PTSEs)—is unavailable. In awake DBS, macrostimulation allows real-time assessment
of both benefits and side effects, including PTSE. Under GA, without patient input,
the PTSE threshold becomes difficult to determine. Intraoperative electromyography
(EMG) can detect PTSE responses, providing a way to monitor and estimate the threshold
for safe and effective stimulation. This case report highlights the value of EMG monitoring
in DBS for ET under GA, emphasizing its role in optimizing lead placement and minimizing
side effects when awake testing is not an option.
Case Report
A 58-year-old male with a history of hypertension presented with tremors involving
the head, jaw, trunk, and upper limbs, sparing the lower limbs. The tremors were of
resting, postural, and action types and had been present since the age of 18. A prior
diagnosis of Parkinson's disease was considered, and a levodopa trial was initiated,
but symptoms were refractory. Based on clinical features—predominantly postural and
action tremors—a diagnosis of ET was made, and DBS targeting the cZI was planned under
GA.
Preoperative 3T magnetic resonance imaging was performed 4 days before surgery. The
patient was induced with propofol and remifentanil (target-controlled infusions, Eleveld
model). After securing the compact head ring and arc adapter plate with a computed
tomography (CT) localizer frame, a contrast-enhanced CT brain was obtained. Imaging
was fused to determine the cZI target coordinates, and a Cosman-Roberts-Wells frame
was applied ([Fig. 1A, B]).
Fig. 1 (A) Cosman-Roberts-Wells (CRW) frame-guided electrode stimulation. (B) Neuroimage guiding coordinate measurements.
Intraoperative EMG was recorded from the facial muscles, upper limbs (biceps brachii,
brachioradialis), and lower limbs (tibialis anterior, extensor digitorum brevis).
Stimulation was delivered using a Boston Scientific Vercise 8-contact lead (185 Hz,
60 µs pulse width), with amplitude titrated from 0.5 mA. EMG response in the limb
muscles was noted at 4.5 mA ([Fig. 2A, B]) left, marking the threshold for PTSEs. The patient was extubated uneventfully.
At 2-week follow-up, stimulation at 4.5 mA reproduced hand twitching, confirming the
PTSE threshold.
Fig. 2 (A) Stimulation settings (Vercise 8-contact lead [185 Hz, 60 µs pulse width], with amplitude
titrated from 0.5 mA). (B) Electromyography (EMG) recordings of left limb muscles noted at 4.5 mA indicating
the threshold for pyramidal tract side effect (PTSE).
Discussion
ET is one of the most common movement disorders, affecting approximately 0.9% of the
general population and up to 4 to 5% of individuals over the age of 65.[2] While medical therapy remains the first line of treatment, a significant number
of patients become refractory to medications and experience disabling tremor. In such
cases, DBS has proven to be an effective therapeutic option. Traditionally, the VIM
nucleus of the thalamus has been the primary DBS target for ET. However, recent studies
have highlighted the cZI[3] as a promising alternative target due to its close proximity to the dentato-rubro-thalamic
tract, enabling superior tremor suppression, especially for postural and action tremors.
Compared with VIM, STN, or GPi, cZI offers a wider therapeutic window and fewer stimulation-induced
side effects. Importantly, cZI stimulation is associated with fewer cognitive, speech,
or gait-related adverse effects, making it a safer and more focused target.
When targeting the cZI during DBS for ET, careful monitoring for PTSEs is crucial.
The cZI lies in close anatomical proximity to the internal capsule, which contains
corticospinal (pyramidal) fibers.[4] Inadvertent stimulation spread to these fibers can lead to side effects such as
muscle contractions, dysarthria, or facial pulling—indicating stimulation-induced
motor pathway involvement. Early intraoperative detection of PTSEs helps refine electrode
placement and optimize programming to achieve maximal tremor suppression while minimizing
unwanted side effects.[5] This is particularly important under GA, recent studies, including the GALAXY randomized
controlled trial, have shown that DBS surgery performed under GA (asleep DBS) offers
clinical outcomes comparable to the traditional awake approach, particularly in terms
of motor improvement and electrode accuracy.[6] Asleep DBS has emerged as a safe and effective alternative, with the added benefit
of being less physically and emotionally taxing for patients, but traditional patient
feedback is unavailable, making objective electrophysiological monitoring even more
essential for safe and effective targeting.
Intraoperative EMG monitoring is a critical adjunct during DBS surgery targeting the
cZI to minimize stimulation-induced motor side effects and optimize electrode placement.
EMG electrodes are strategically placed on muscles representing corticospinal and
corticobulbar innervation, commonly including facial muscles, as well as upper limb
and lower limb muscles. High-frequency stimulation (185 Hz) was delivered sequentially
to each contact and directional segment, starting at 0.5 mA and gradually increasing
up to 5 mA or until side effects are observed; higher frequencies can be used for
chronic therapy but low frequency is better for intraoperative testing in awake patients.[7] The presence of time-locked EMG responses to stimulation pulses indicates spread
of current to motor pathways, establishing threshold amplitudes for motor activation.
Contacts eliciting EMG activity at lower stimulation amplitudes are avoided, while
those that do not provoke muscle activation within therapeutic ranges are preferred
for chronic therapy. Directional programming further refines stimulation by steering
current away from structures inducing motor side effects. This systematic EMG-guided
approach enhances intraoperative decision-making, facilitating precise lead positioning
and improving clinical outcomes in cZI DBS procedures.
In our case, EMG monitoring successfully detected stimulation-induced PTSE, allowing
estimation of the threshold for PTSE without patient input. This highlights the value
of EMG in asleep DBS for optimizing lead placement and minimizing side effects when
awake testing is not possible. In this case, evoked potentials such as somatosensory-evoked
potentials or motor-evoked potentials were not utilized because the primary intraoperative
objective was to detect PTSE related to spread of stimulation, rather than monitor
the integrity of long tract conduction pathways. Unlike evoked potentials, EMG allows
real-time, contact-specific evaluation of motor side effects during stimulation mapping
as patient is under GA.
Conclusion
This case underscores the importance of accurately identifying the PTSE threshold
during DBS targeting the cZI for ET. Due to the close proximity of the cZI to the
internal capsule, inadvertent stimulation can easily spread to corticospinal fibers,
causing unwanted motor side effects. Intraoperative EMG monitoring played a pivotal
role in objectively detecting the PTSE threshold in this asleep DBS procedure, enabling
precise electrode placement without relying on patient feedback. Recognizing this
threshold is essential to maximize tremor suppression while minimizing stimulation-induced
muscle contractions or other motor complications. This case reinforces that EMG-guided
detection of PTSE thresholds is a critical safety measure in asleep cZI DBS, helping
to optimize therapeutic outcomes and reduce adverse effects.
