Keywords
Deep Brain Stimulation - Parkinson Disease - Neurosurgery
Palavras-chave
Estimulação Encefálica Profunda - Doença de Parkinson - Neurocirurgia
INTRODUCTION
The introduction of fully implanted deep brain stimulation (DBS) systems in clinical
practice in the 1970s led to a paradigm shift in the treatment landscape of a variety
of neurological and psychiatric disorders, including pain, epilepsy, and movement
disorders, such as tremors, Parkinson's disease (PD) and dystonia.[1] Over these decades, DBS became a well-established therapeutic option, and its' indications
and scope of use broadened, leading an estimated number of DBS systems implants worldwide
to reach more than 200.000 in 2021.[2] Along with its' increased recognition as a powerful treatment choice, the complexity
and sophistication of newer systems continued to expand substantially.
This review is the second part of a broad effort to document and integrate the basic
fundamentals and recent successful developments in the field. This part of the review
will focus on classic basic choice paradigms for electrode placement as well as new
exploratory targets, mechanisms of neuromodulation using this technique and new developments,
including focused ultrasound-driven ablative procedures.
CHOOSING TARGETS FOR DBS IN PD
CHOOSING TARGETS FOR DBS IN PD
In PD, the subthalamic nucleus (STN) or the internal part of the globus pallidus (GPi)
are the preferred and most effective targets for alleviating the cardinal Parkinsonian
signs of bradykinesia, tremor, rigidity, as well as levodopa-induced dyskinesia (LID).[1] In addition, in selected cases, DBS electrodes can be implanted in other brain locations,
such as the thalamus (e.g., for tremor dominant PD), the caudal zona incerta, and
the pedunculopontine nucleus (currently an experimental target for gait problems,
and postural instability).[3]
[4]
[5]
[6] The choice of the target adds another layer of complexity and should be discussed
and decided according to nuances of clinical presentation, specialist preferences,
and individualized profile to each case.
STN and GPi
DBS of both STN and GPi have been proven to be similarly effective treatment choices
for patients with PD, although subtle but important outcome differences exist.[7]
[8]
[9] Overall, STN DBS tends to be preferred for control of resting tremor and rigidity,
allowing for a greater reduction in dopaminergic medication dose, which may be beneficial
but also a potential source of worsening of axial motor signs and certain nonmotor
symptoms. As such, STN DBS-related complications include apathy, depression, impulsivity,
worsened verbal fluency, and executive dysfunction in a subset of patients.[10]
[11] Another variable to be considered is the fact that the STN, being a smaller target,
tends to require a lower amount of electrical stimulation, potentially requiring less
frequent battery replacements.
GPi DBS tends to be preferred to approach cases with disabling LID, especially in
patients using relatively low doses of levodopa and a low threshold for these complications.[12] Additionally, it may be beneficial for cases with “off” dystonia, and when mood
and cognition are concerning.[13] A recent meta-analysis of the clinical trials concluded that STN and GPi have very
similar benefits, with STN favoring medication reduction, but GPi favoring better
behavioral outcomes.[14] These findings are supported by randomized clinical trials showing that GPi and
STN are equally effective targets for the treatment of PD motor symptoms and LID.[15] Other studies, however, show subtle differences, as in the case of a Dutch (NSTAPS)
trial[13] comparing DBS of these targets in advanced PD patients, where, patients receiving
STN DBS had a more substantial improvement in motor symptoms in the long term, than
those treated with DBS of the GPi, despite no between groups statistically significant
differences in quality of life or the incidence of adverse events.[15] In contrast, a different prospective randomized study of unilateral stimulation
of the STN and GPi found similar effects on mood and cognition, while GPi DBS led
to a more pronounced improvement in the quality of life and less negative influence
on verbal fluency.[16] Finally, a trial comparing 24-month outcomes for 299 patients who underwent bilateral
DBS of both targets found similar improvements in motor function, maintained at the
end of the follow-up period for both targets. As expected, dopaminergic medication
was decreased more for the STN DBS group, while visuomotor processing speed declined
less after GPi DBS.[17]
Ventral intermediate nucleus of the thalamus (VIM)
Reflecting what was described by the pioneer study of Benabid et al.[18] in essential tremor, high-frequency stimulation of the VIM improves tremor in PD.
However, as it typically does not interfere significantly with other PD cardinal signs
or dyskinesia, VIM DBS has been reserved for cases of tremor-dominant PD.[11] In a long-term study following stimulation of the VIM for severe tremor, including
patients with PD, essential tremor, and post-traumatic tremor, reported an initial
adequate response regarding tremor suppression overall in the whole group of patients.[19] The study compared these findings with their own results in patients with PD treated
with STN DBS, concluding that the latter was an adequate target due to the added improvement
in other motor symptoms, such as rigidity and bradykinesia. A different study comparing
thalamotomy versus thalamic DBS in 45 PD patients, revealed the same efficacy for
tremor suppression from each of the two procedures at five years.[16] Similarly, the multicenter European study of VIM DBS in PD and essential tremor
patients studied 73 patients with Parkinsonian tremors who underwent VIM stimulation,
demonstrating that tremors in the upper and lower extremities were significantly reduced
without any interference with other Parkinsonian features.[19]
EXPLORATORY TARGETS
Pedunculopontine nucleus (PPN)
The PPN has initially gained attention as a potential target for the improvement of
axial signs of PD, particularly gait impairment and freezing of gait (FOG),[3]
[5] which are typically late issues not adequately addressed by STN or GPi stimulation.[8] The PPN is a brainstem area involved with locomotion, sensory, and behavioral processing,
connecting the basal ganglia and the spinal cord.[20] Initial experimental case series of PPN DBS in PD showed subtle changes in gait
parameters, added by subjective reduction in falls in spite of no other impact on
PD symptoms.[8] Combining stimulation of the PPN and STN seems to provide additional motor benefit.[3] A review commissioned by the Movement Disorders Society to evaluate the utility
of stimulating the PPN across centers found evidence that this procedure improves
FOG, however, the degree of improvement varied within and between centers. The evidence
did not support any broader benefit on other symptoms of PD, such as limb akinesia,
rigidity, or tremor,[20] and did not impact allowing for a reduction in dopaminergic therapies dose. As such,
there is no consensus on proper patient selection, ideal area for stimulation within
the target, how to target it accurately, need for co-stimulation of other nuclei,
and long-term outcomes.
Caudal zona incerta (cZi) / Posterior subthalamic area (PSA)
A limited number of studies found promising results from DBS of the posterior subthalamic
area (PSA), including the caudal zona incerta (cZi) and prelemniscal radiation.[21] Anatomically, the zona incerta region lies dorsal and posterior to the STN and is
located at the junction of basal ganglia thalamocortical and cerebellar thalamocortical
circuits making it an interesting target, strongly linked to tremor pathophysiology.
This rationale seems to be effectively translated into clinical evidence. For example,
DBS of the cZi was performed in 14 tremor-dominant PD patients with assessments at
baseline on and off medication, followed for at least one year after surgery.[21] At the 18-month follow-up, the UPDRS III score improved by 47.7%, while individual
scores for contralateral tremor, rigidity, and bradykinesia were improved by 82.2%,
34.3%, and 26.7%, respectively. Another randomized trial comparing cZi stimulation
with the best medical treatment found a striking benefit for tremor control despite
no significant reduction in medication dosage.[22] A different study compared the UPDRS scores for patients undergoing cZi DBS with
a cohort of STN DBS patients.[23] The results showed superiority of cZi stimulation over STN stimulation for improving
contralateral parkinsonism signs overall. Total UPDRS score improved by 76% for cZi
stimulation compared with 55% for STN, while tremor scores improved by 91% for cZi
compared with 61% for STN DBS. On the other hand, differences in scores for bradykinesia,
dyskinesia, and reduction in dopaminergic medication dose did not reach statistical
significance. As such, cZi DBS seems to be a safe and powerful target for patients
with severe Parkinsonian tremors.[21]
[22]
[23]
Nucleus basalis of Meynert (NBM DBS)
DBS of the nucleus basalis of Meynert (NBM) has been proposed as a treatment option
for PD dementia (PDD) and other cognitive dysfunctions. The NBM is a discrete anatomical
structure in the basal forebrain, located inferior to the posterior GPi, and provides
the major source of cholinergic innervation to the cortical mantle. Lately, evidence
has supported the exploration of DBS to this structure as a potential therapy for
PDD. A randomized, double-blind, crossover clinical trial evaluated the results of
6 patients with PDD.[24] No serious adverse events were reported in this trial and an improvement in scores
on the Neuropsychiatric Inventory was observed compared with sham stimulation and
the preoperative baseline. However, no improvements were observed in the primary cognitive
outcomes. Another study suggests that NBM DBS is safe and feasible, and stimulation
was associated with reduced right frontal and parietal glucose metabolism (p < 0.01) and increased low- and high-frequency power and functional connectivity,
concluding that NBM stimulation altered neuroimaging biomarkers but without lasting
cognitive improvement.[25] Further studies with larger sample sizes and control groups are necessary to understand
the optimal stimulation of the NBM and to assess if DBS stabilizes or reverses cognitive
decline in PD compared with the best medical therapy.
Other experimental brain targets for stimulation therapy in PD, such as CM/pf[26] of the thalamus and spinal cord[27] currently have limited evidence for efficacy.
MECHANISMS OF DBS
Over the last few decades, findings from DBS recordings of local field potentials
(LPF) and multi-unit activity have led to new insights into basal ganglia circuitry
and the pathophysiology of PD. The current concept emphasizes the neuronal firing
pattern and synchronized oscillatory activity. In either STN or GPi, a synchronized
oscillatory activity within β frequency (13 - 30Hz) has been proposed as a neurophysiological
abnormality underlying PD symptoms.[28]
[29] Furthermore, it has been demonstrated that this β activity in the STN is a marker
of a hypodopaminergic state,[30] correlating with responsiveness to levodopa.[31] Additionally, studies suggest that this firing pattern occurs in the off state and
is suppressed by administration of levodopa, as well as by high-frequency stimulation
in the STN.[32] These studies of LFP recordings from the STN in PD patients after administration
of levodopa or apomorphine have shown that switching from off to on state correlates
with a change in the firing pattern, with a reduction of β activity, which is replaced
by γ activity (60 - 80Hz). Finally, in patients who develop levodopa-induced dyskinesia,
the hyperkinetic movements are associated with θ activity (4 - 11Hz) in bilateral
or contralateral STN implicating this firing rate band as a potential marker of dyskinesia
in PD.[33]
Other than these physiological findings, distinct DBS mechanisms accounting for the
positive effect of DBS have been proposed. One of such mechanisms is the functional
inactivation of neuronal populations near the electrodes. This has been largely attributed
to the so-called depolarization block, a state in which cells undergo depolarization
with an almost complete abolishment of spontaneous action potentials. Another commonly
proposed mechanism underlying the effects of DBS at high frequency is the excitation
of fiber pathways in the vicinity of the electrodes (afferent and efferent projections
from targeted regions and fibers en passant). This is an interesting possibility, as the anterograde and retrograde propagation
of action potentials along such structures may influence the physiology of brain regions
projecting to or receiving projections from the original point of stimulation.[34] The behavioral consequences of exciting axonal pathways may not always be positive,
as a stimulation-induced tonic-firing pattern may supplant physiologic rhythms. In
certain pathological states, however, the implementation of artificial brain rhythms
after stimulation may be beneficial, disrupting abnormal pathologic oscillatory patterns
and improving clinical outcomes, as in the example of β oscillations in PD.[35]
Additionally, metabolic and neurochemical changes in structures at a distance from
the target have also been suggested to contribute to DBS's mechanisms in different
contexts related to this treatment modality.[34]
[35]
POSTOPERATIVE MANAGEMENT
Despite long-term experience with DBS in PD, there is a considerable lack of formal
universal guidelines for the management of stimulation and medication in the postoperative
periods. Most expert centers, however, follow standardized algorithms that often vary
between institutions.
Timing and schedule for DBS programming
The optimal moment to start the stimulation process may vary between centers with
some starting the day after surgery while the patient is still admitted, while others
wait until the insertional/lesional effect, which can last up to two months, subsides.
The latter is probably the most common approach as this lesional effect induced by
changes in tissue impedance around the electrode may interfere with the parameters
used to determine the window between therapeutic and adverse effects. This is a cornerstone
to start effective and successful DBS treatment, serving also as guidance on chronic
parameters and future adjustments. As such, a reasonable time interval between surgery
and the beginning of therapy ranges between 4 to 8 weeks.[36]
Accordingly, chronic stimulation should be started at the contacts with the lowest
thresholds for clinical benefit and the highest thresholds for adverse effects. Pulse
width and rate (frequency) values should be kept constant and, despite the fact that
there are no evidence-based guidelines to define these specific parameters, most centers
use a frequency of 130Hz and pulse width of 60 μs, which are effective for the majority
of cases. In PD, stimulation should start with low amplitudes, which are gradually
increased in the subsequent weeks. The typical initial montage should be in a monopolar
pattern with the case as anode and one active contact as a cathode, which provides
a spherical electrical field around the selected electrode. A bipolar configuration
(one contact as a cathode and another as anode) should be used to narrow the electrical
field, avoiding the spread of the current and consequent adverse effects.[37] More advanced settings are possible, including double-monopolar, interleaving, and
guarded cathode, which are rarely used in first programming sessions. Other strategies
can be used for initial programming, for instance with imaging guidance and volume
of tissue activation models and based on sensing of β activity from devices with LFP
detection technology. These alternative forms have not yet been widely adopted.[37]
It is highly recommended that after initial settings are activated, patients take
their first regular dose of dopaminergic drugs and wait in the clinic until peak dose
effect is reached. This will allow the observation of acute but non-immediate adverse
effects such as severe dyskinesia induced by the combination of stimulation and medication.
The most common stimulation-induced complications observed during programming sessions
include worsening of axial symptoms, dyskinesias, speech dysfunction, oculomotor/periorbital
muscle activation, and contractures due to internal capsule stimulation.[38] These symptoms can be minimized or avoided by standard adjustment in stimulation
parameters depending on specific situations. As mentioned above, stimulation-induced
dyskinesias are common after STN DBS and can be minimized by different stimulation
strategies or medication adjustment, while, on a positive note, they can be seen as
indirect signs of accurate electrode placement.[39]
Medication management
The initial medication adjustment is performed in parallel with the initial programming
sessions by a neurologist familiar with the management of PD and DBS. Again, there
are no rigid formal guidelines for the management of medication after DBS. In patients
with STN DBS, a reduction in dopaminergic therapy of 40 to 60% is usually achieved
within weeks or a few months after surgery.[40] The reduction in PD therapy dosage begins when the amplitude of stimulation is increased
to a level that provides symptomatic relief of motor symptoms and fluctuations, which
often happens following the second programming visit. The sequence and form of medication
reduction are usually individualized according to the patient's symptoms, profile,
and regimen. It is reasonable to focus on one drug class at a time to minimize adverse
reactions and withdrawal symptoms.[41] For example, anticholinergics and MAO inhibitors can be the first to be titrated
down, followed by COMT inhibitors, amantadine, and then, reduction in levodopa and
dopamine agonist.[42] Again, this sequence is a generic suggestion that needs to be carefully revised
individually and includes many exceptions. For instance, in patients with a history
of impulse control disorders, dopamine agonists are usually discontinued with great
caution earlier after surgery.
During this phase, patients should be closely monitored, not only due to the risk
of early medication withdrawal but also given the occurrence of behavioral changes
(depression, suicide risk, apathy, fatigue, etc.) associated with pronounced and abrupt
medication reduction, downregulating mesolimbic dopaminergic denervation.[40]
[41]
[42]
[43] A low dose of dopamine agonist has shown to be effective in managing withdrawal
hypodopaminergic behaviors in this setting.[42] Conversely, some patients tend to develop hyperdopaminergic behaviors such as euphoria
and hypomanic states, which seem to be more associated with the surgical procedure
itself and the location of the stimulating contacts within the limbic segments of
the STN.[44]
ADVANCES IN DBS THERAPY
Recent advances in technology and technique have continuously been implemented in
new generations of DBS systems, increasing therapeutic yield and improving management
of adverse effects, reducing patient burden, and clinician programming times. These
advances include current delivery devices, directional leads, new exploratory targets,
programming approaches based on the volume of tissue activation models, insertion
techniques, and identification of better biomarkers for patient selection and prediction
of outcomes.
Directional stimulation
Conventional DBS systems utilize ring-shaped electrodes, which produce omnidirectional
spherical electric fields with little additional control of the shape of the volume
of tissue activated. Directional leads differ in that they allow for horizontal current
steering via changes in electrode design, allowing the electric field to deviate away
from structures that induce undesirable side effects. Of importance, these systems
place directional leads at the two middle contact levels, while the most ventral and
the most dorsal ones retain the ring-mode design distributing the current radially.[45]
[46]
These advances in technology come at a cost. For instance, an increase in patient's
expectations gives the false impression that the device can allow for an unrestricted
fix of stimulation and disease-related problems. Also, despite the fact that the current
steering capability allows for some degree of rescue of the therapeutic effect of
misplaced electrodes, precise targeting of brain nuclei should continue to be the
goal. Finally, it should be kept in mind that programming is becoming increasingly
more sophisticated and challenging in terms of demand for time, complexity, and need
for advanced expertise. The real advantage of this technological advance needs to
be firmly confirmed in clinical practice.
Adaptive or closed-loop stimulation
The existent model of DBS involves continuous stimulation input, which does not consider
real-time pathophysiological phenomena recorded using LFP of the brain areas being
stimulated, such as β oscillatory activity, a marker of the therapeutic effect of
levodopa. In the adaptive DBS paradigm, DBS is activated based on electrophysiological
feedback parameters indicating its need. This approach was initially tested on a primate
animal model of PD using closed-loop stimulation of the GPi based on ongoing activity
in M1, an approach that proved to be more efficient overall in alleviating motor symptoms
than traditional open-loop stimulation.[47] Besides, a greater reduction of pathological oscillatory activity in the pallidum
and primary motor cortex with closed-loop stimulation versus open-loop stimulation
was documented.[47] Another study found that a small sample of PD patients who underwent closed-loop
stimulation had significantly greater improvement of the PD cardinal symptoms with
fewer adverse effects, as compared with when they underwent open-loop stimulation.[48]
In summary, the limited but consistent body of literature regarding this technique
promises considerable advantages (reduced adverse effects, optimal clinical benefit
stimulation delivery to match the patient's fluctuations, and extended battery life)
and also allows us to improve our understanding of functional (and malfunctioning)
neurocircuitry.[49]
Interleaving stimulation
The technique of interleaved stimulation entails running two programs with different
settings on the same lead in a temporally alternating sequence, dictated by the programmed
frequency. This allows for additional flexibility in creating and reshaping the electrical
field along the longitudinal axis of a multi-contact ring electrode, keeping in mind
that it does not allow horizontal current steering in any shape or form.[50] The utility of this programming variation can be theoretically useful in two scenarios:
-
• stimulation of different brain regions with individualized settings of amplitude
and pulse width to alleviate symptoms and signs that are driven by specific and separate
areas around the core of the stimulated nuclei (i.e., stimulation of the ventral and
dorsal STN to control dyskinesias and parkinsonism).[51]
[52]
[53]
MRI-guided and CT-verified DBS implantation in asleep patients
Awake intraoperative microelectrode recording combined with macro stimulation is the
most common technique used by most centers to compensate for imaging limitations and
subtle stereotactic incongruences needed for optimized electrode placement. On the
other hand, awake mapping can be poorly tolerated by a minority of DBS surgery candidates
due to claustrophobia, anxiety, high-amplitude tremor, or painful dystonic posturing.[54] In these instances, considering DBS with general anesthesia has emerged as an option.[55] This technique often is coupled with real-time intraoperative MRI or CT scanning,
while commercially available options for intraoperative imaging are gaining visibility
including operating rooms with mobile magnets,[56] and implantation using a CT-guided approach.[54]
[55]
[56]
[57] However, the safety and clinical outcome of this technique remains a matter of debate.[57]
[58] In a single-center study, the authors found no difference in complication rates
between asleep and awake DBS, but the study did not evaluate the motor outcomes between
the two cohorts.[59]
[60] Similarly, a study using frame-based DBS implantation under general anesthesia with
intraoperative MRI verification of lead location demonstrated that this technique
is safe, precise, accurate, and effective compared with standard implantation performed
using awake intraoperative physiology.[61] However, another study suggested that there might be a lower overall intraoperative
complication rate with asleep DBS but at the cost of a higher rate of postoperative
stimulation-related complications compared with awake DBS.
MR-GUIDED FOCUSED ULTRASOUND
MR-GUIDED FOCUSED ULTRASOUND
The potential effect of focused ultrasound (FUS) in heating live tissues was first
recognized when high-intensity ultrasound waves were used in submarines during World
War II, as it was noticed that it could heat up and kill marine life.[62] In the early 1950s, FUS was experimentally tested on body tissues as an alternative
to ablative procedures, including lung and brain.[63] At the time, the technique was more “invasive,” requiring a craniotomy to allow
the ultrasound energy to reach the target, ultimately leading to the understanding
that it was not overall more advantageous compared with traditional radiofrequency
ablative surgery.[64]
[65] Over the decades since then, steady advances in technology allowed accurate targeting
of deeper structures in the human body, eventually to leading the current use of the
magnetic resonance-guided focused ultrasound (MRgFUS) technique as a form of non-invasive
stereotactic ablative procedure on a wide range of indications.[66]
The principle of FUS relies on its ability to induce cytotoxic levels of increased
tissue temperature with a relatively low risk of vascular vulnerability. As a consequence,
this technique can be more precise than others, such as gamma knife radiosurgery,
culminating with the submillimeter precision capability of modern devices.[65] As such, based on solid and sound scientific evidence, MRgFUS has been approved
by various health agencies worldwide for the treatment of essential tremor (ET) and,
more recently, PD.
The first series of MRgFUS thalamotomy in tremor-dominant PD was published by Schlesinger
et al. in 2015.[63] This pilot study of seven cases followed for up to 12 months (mean 7.3 months) showed
mean PDQ-39 and total UPDRS scores improvement by almost 50% for both scales comparing
preoperative and 1 week postoperatively. Three of these cases presented subtle reemergence
of tremor at 1 week, 1 month, and 6 months after the procedure, respectively. Otherwise,
there were no permanent adverse effects. The same group published another study with
12 tremor-dominant PD cases in 2018, now with a longer follow-up (mean 11.5, ranging
from 6–24 months).[64] Again, mean motor UPDRS and PDQ-39 scores improvements were significant, reaching
46.2% and 46.6%, respectively, after 6 months postoperatively. A third of these cases
experienced tremor recurrence within 6 months after the procedure, which continued
to be significantly less disabling compared with preoperative baseline. Fasano et
al.[65] published a single-blinded prospective study of three tremor-dominant PD cases with
follow-up of up to six months. The reduction in tremor scores was in the range of
50%, inducing an improvement of 32.3% in the activities of daily living section of
the UPDRS from baseline to the latest follow-up. Both mild, transient, and more significant
and long-lasting complications were observed in single cases, in addition to tremor
recurrence in one of these cases. In the same year, a double-blinded, sham-controlled
randomized trial of MRgFUS thalamotomy in tremor-dominant PD was published, including
27 patients reporting a 62% improvement from baseline to 3 months postoperatively
in tremor scores, compared with 22% in the sham group. Persistent adverse events of
thalamic lesion included paresthesia in 19% and ataxia in 4%,[67] in STN adverse events can occur as dyskinesias, weakness, speech, and gait disturbance
which in the majority of the cases are transient and last for a few weeks.[68]
The first report of unilateral MRgFUS pallidotomy for PD was published in 2015, of
a 55 years old patient with severe motor fluctuations and levodopa-induced dyskinesias.
The outcomes at up to 6 months were very significant, including a reduction of 61%
in the UPDRS motor scores and of 76% in dyskinesia (UPDRS part IV) scores after 6
months.[69] Later, a series of 10 cases of PD treated with unilateral MRgFUS pallidotomy was
published in 2018 with peak dose dyskinesias severity as the main treatment outcome.
Patients were followed for 12 months with significant improvements of 32.2% in the
off-medication condition motor scores and 52.7% in dyskinesia scores, which correlated
with improvement in quality of life. None presented persistent adverse effects.[70] Although the worldwide experience with this technique and target in PD is growing,
the overall impression is that it compares to radiofrequency pallidotomy in terms
of effectiveness but may be more advantageous from the standpoint of safety.
Unilateral MRgFUS subthalamotomy has only been studied in one open trial with a series
of 10 PD patients showing an improvement of 53% in motor UPDRS scores on the contralateral
body side in the off-medication condition 6 months after the treatment. One patient
developed transient contralateral hyperkinetic movements after the procedure.[69] This is a promising target for MRgFUS in PD, however, most of the exiguous literature
on this specific topic and target comes from a single center and requires further
exploration. A comparison between MRgFUS and DBS can be found in [Table 1].
Table 1
Comparing MRgFUS and DBS
|
MRgFUS
|
DBS
|
|
Clinically used in PD since 2018 with limited experience and availability
|
Clinically used in PD since 1994 with broad worldwide experience
|
|
Stereotactic frame needed
|
Stereotactic frame needed
|
|
No incision needed
|
Incision needed
|
|
One step procedure
|
One or two steps procedure
|
|
No implantable device needed
|
Implantable device needed
|
|
Currently unilateral
|
Bilateral procedure, if indicated
|
|
Lower incidence of acute complications
|
Higher risk (+/− 5%) of acute complications
|
|
Effect depends on lesional effect (ablation)
|
Effect depends on electrical stimulation /transient microlesional effect
|
|
Irreversible
|
Reversible
|
|
Immediate therapeutic effect
|
Therapeutic effect requires stimulation onset and optimization
|
In conclusion, DBS has become an established therapy for PD over the past decades,
with good quality evidence for STN and GPi as the primary targets to address PD cardinal
signs, motor fluctuations, and LID. Therapy with DBS is an ongoing process of refinement
and sophistication in terms of technical development and in several clinical aspects
such as selection of patients, choice of targets, and exploration of stimulation paradigms.
One of the main dogmatic changes in the field was its consideration for patients with
shorter disease duration, after motor complications develop, instead of later on,
when the disease is too advanced, and results are suboptimal. As a dynamic field,
further developments are expected in the near future, hopefully broadening these options
for physicians and patients. Despite all the progress, access to DBS therapy is still
limited in developing countries and remote areas, either due lack of awareness and
scarce financial, logistic, and manpower resources. This review aimed to help fill
in the knowledge gap, covering the fundamental aspects of DBS for the management of
PD.
Bibliographical Record
Mariana Moscovich, Camila Henriques de Aquino, Murilo Martinez Marinho, Lorena Broseghini
Barcelos, André C. Felício, Matthew Halverson, Clement Hamani, Henrique Ballalai Ferraz,
Renato Puppi Munhoz. Fundamentals of deep brain stimulation for Parkinson's disease
in clinical practice: part 2. Arq Neuropsiquiatr 2024; 82: s00441786037.
DOI: 10.1055/s-0044-1786037
