Discussion:
Different studies have revealed approximate circuits of tics, OCD and
also TS which are generally known as CSTC circuit [1-3]. CSTC
components including thalamus, posterolateral GPi and anteromedial GPi
are among the most used targets for DBS procedure in TS, while other
targets including subthalamic nucleus (STN), globus pallidus Externus
(GPe), anterior internal capsule (ALIC), and nucleus accumbens (NA) are
also considered useful in some studies [2]. It has been shown that
stimulation of each target would lead to an improvement in specific set
of components of the disease (e.g. tics, OCD and etc.) while it varies
in different cases [2].
Anteromedial GPi is mostly known
as an effective target for improvement of tic component of TS, while
some studies have stated its ineffectiveness [2, 3]. Stimulation of
anteromedial GPi also has been shown to be an effective target in the
treatment of the isolated OCD [4], whereas the studies with the
purpose of TS treatment have mentioned no significant improvement in the
OCD component of TS [2]. Consequently, there is no a consensus yet
on how stimulation of anteromedial GPi affects different components of
TS (either tics or OCD) although is it generally thought to be effective
in TS treatment [3].
In the current case, fluctuations and variations in the therapeutic
outcome of TS components have been observed, depended to the stimulation
parameters. During sessions, the optimal setup was achieved based on
alterations in symptoms and patient’s compliance. With this setup,
stimulation of anteromedial GPi led to significant improvement in OCD,
but the tics were still existed and got worse progressively. To the best
of our knowledge, stimulation of GPi with similar therapeutic outcome
has not yet been reported.
In spite of many studies on how CSTC circuit may play an important role
in Tic, OCD and TS, our observation along with many others are still
needed to be explained in terms of variations in therapeutic outcomes.
Many neural pathways are connecting different and specific parts of
cerebral cortex, striatum and thalamus together, making multiple
parallel and integrated circuits [5-7]. As an example, some areas in
GPi, projects neurons to specific parts of thalamus [5] and the same
interconnections would exist between thalamus and cerebral cortex
[7], GP and other part of striatum [5], GP and thalamus [5]
and also in GP itself [5]. In this case, there exist multiple neural
pathways between cerebral cortex, striatum and thalamus, involving
specific part of each.
Among all these complicated circuits, some specific areas and pathways
are related to either tic or OCD pathophysiology and some others are in
common; while a portion of them remains unrelated to both. To be more
detailed, anterior cingulate cortex, dorsal lateral prefrontal and
lateral orbito-frontal areas are related to both OCD and tic disorders
[1] which we intend to call them common areas; while, motor and
oculomotor areas are mostly related to tic disorder [8] and
ventromedial prefrontal cortex is mostly the characteristic of OCD
[4]. Interestingly, common areas including lateral orbito-frontal
area and anterior cingulate cortex are responsible for reward processing
and fear expression, respectively, which are common features and
underlying causes of both tics and OCD, whereas motor functions in tics
may be subsequent to involvement of motor cortex and unwanted
reoccurring thoughts in OCD may be due to the involvement of limbic
system specifically [1, 4, 8].
Anteromedial GPi is related to associative, motor and limbic areas
through pallidothalamic and thalamocortical pathways [5-7, 9]. These
pathways and areas may include the pathways or areas that are involved
in the pathophysiology of either tic or OCD, or both. Therefore,
Anteromedial GPi might be related to both common and tic-/OCD-specified
areas and pathways and neural impulses from anteromedial GPi would find
their way through specific neural pathways of pallidothalamic and
thalamocortical pathways toward tic-/OCD-specified or common pathways
and areas. DBS studies have also demonstrated that anteromedial GPi is a
beneficial target for both tic and OCD [10] which indicates its
involvement in both tic and OCD generating pathways and areas .
Here, we have hypothesized that through DBS procedure on anteromedial
GPi, the stimulation impulse would travel through all possible related
pathways to anteromedial GPi, including common or tic-/OCD-specified
pathways and make an impact on any of them (figure 1). This impact may
end up with an appropriate therapeutic outcome in either tic or OCD, or
both in respect to physiological conditions of the pathways. In other
words, physiological conditions of these pathways determine the
variations in the therapeutic outcome. Moreover, it is probable that all
tic or OCD generating circuits do not possess similar physiological
conditions which leads to different responsiveness to certain stimulus.
It can be said that specific stimulation adjustment may cause
resynchronization as a probable effect in set of pathways, but causing
no effect in the others in respect to their physiological condition. In
our case, firstly we observed fluctuations in symptoms and eventually at
the best adjustment, OCD improved significantly while tic remained
unchanged. We think that stimulation of anteromedial GPi spread out to
both tic-/OCD-specified pathways; and these pathways respond to the
stimulus differently based on their physiological condition which led to
fluctuations in symptoms. In other words, with certain adjustments,
OCD-specified pathways probably resynchronized and improved better than
tic-specified pathways in response to the stimulus because of the
former’s higher susceptibility to this event, leading to an improvement
in OCD and not tic. In conclusion, we hypothesize that the anteromedial
GPi can be described as a portal to the pathways involved in both tic
and OCD and stimulation of this target would make an impact on all these
pathways but with different extents. Hence, anteromedial GPi itself is
not the determining factor in improvement of OCD or tic components of TS
and the condition of involved pathways is playing an important role.
This hypothesis would also explain variations in therapeutic outcomes of
DBS for TS patients in other studies.