Key-words:
Deep brain stimulation - tremor - ventral intermediate nucleus of the thalamus
Introduction
Tremor is defined as a rhythmic, sinusoidal oscillation of a body part and has been
reported as one of the most common movement disorders encountered in the clinical
practice. The classification and differentiation of atypical, intricate, and uncommon
tremors can be challenging, and the differential diagnosis hinges on the acquisition
of a detailed examination that focuses attention on tremor topography, frequency,
amplitude, and associated features.
Conventionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered
the target for deep brain stimulation (DBS) for most tremor syndromes. This clinical
practice of using VIM has been largely based on the excellent tremor outcomes in patients
with refractory essential tremor (ET).[[1]] Nevertheless, despite the exceptional results observed in some patients, thalamic
stimulation might not successfully treat all patients. In addition, uncommon forms
of tremors remain a treatment challenge. Thalamic lesioning surgery and DBS for complex
tremor syndromes have yielded mixed and in many cases disappointing results.[[2]],[[3]] Larger lesions (e.g., thalamotomy) or areas of stimulation have been commonly required
to treat both distal and the more difficult problem of proximal tremor.[[4]],[[5]] Larger lesions or wider zones of electrical stimulation can potentially lead to
an increased risk of adverse events.[[6]],[[7]]
Case Report
A 68-year-old female presented with resting and positional tremors with no parkinsonian
symptoms. Medical therapy with trihexyphenidyl HCl, levodopa/carbidopa hydrate, and
arotinolol was prescribed for outpatient use but was not clearly effective. Institutional
ethical clearance and patient's consent for publication were taken for the same. Left
VIM thalamus DBS was performed in December 2016 with near abolition of tremors in
her right hands and legs. She was later planned for right VIM thalamus DBS after 2½
months. Leksell frame was applied and affixed to the patient's head after administration
of a local anesthetic (1% lidocaine). Computed tomography scan performed after marking
the anterior commissure-posterior commissure (AC-PC) line. Target coordination was
14 mm lateral to AC-PC line, 6 mm posterior to midpoint, and 0 mm above the AC-PC
line [[Figure 1]]. Microelectrode recording showed that unit activity was discriminated throughout
the tract. VIM activity was obtained, including unit responded to the passive movement
of hand. Two tremor-related cells were found in the ventral portion of VIM. Ventral
capsule (Vc) activity was not recorded. Result was seen as abolition of tremors in
hands, recording of rhythmic discharges, and anatomometry with X-rays, depicting the
position of microelectrode. Stimulation was done with 3.2 mA and 180 Hz for a duration
of 60 μs. By combining microelectrode recording and stimulation technique with conventional
X-ray, DBS lead was placed through the first track. Finally, a programmer was implanted
in the chest in subcutaneous plane under general anesthesia, and its cable was connected
to the DBS lead.
Figure 1: Coordinates for right ventral intermediate nucleus thalamic deep brain stimulation
Discussion
ET is a postural disability that is inherited in an autosomal dominant pattern in
approximately two-thirds of cases, and the age at onset is most commonly in young
adulthood. The tremor frequency is 4–12 Hz, and it usually resolves with limb support
and at complete rest.[[8]] The upper extremity is affected in 90% of cases, the head in 40%, and the voice
in 30%. Alcohol and beta- adrenergic receptor antagonists often adequately suppress
ET.[[9]] Although the pathogenesis of this disorder is unknown, the olivo-cerebello-rubral
loop and the cerebellum are believed to be critical in the development of ET.[[8]] DBS has become a standard therapy for the treatment of selected cases of medication-refractory
ET. Conventionally, the ventralis intermedius nucleus (VIM) of the thalamus has been
considered the main target for medically intractable tremors.
There are some drugs which have been tried in the treatment for ETs such as beta-blockers
such as propranolol (Inderal) which help relieve tremors in some people. Beta-blockers
may not be an option if you have asthma or certain heart problems. Side effects may
include fatigue, lightheadedness, or heart problems. Other drugs as primidone (Mysoline)
may be effective in people who do not respond to beta-blockers. Other medications
that might be prescribed include gabapentin and topiramate. Side effects include drowsiness
and nausea, which usually disappear within a short time. Alprazolam and clonazepam
may be used to treat people, for whom tension or anxiety worsens tremors. Side effects
can include fatigue or mild sedation. These medications should be used with caution
because they can be habit-forming. Botox injections might be useful in treating some
types of tremors, especially head and voice tremors. Botox injections can improve
tremors for up to 3 months at a time.
Physical therapists can teach exercises to improve muscle strength, control, and coordination.
Occupational therapists can help adapt to living with ET. Therapists might suggest
adaptive devices to reduce the effect of tremors on your daily activities, including
heavier glasses and utensils, wrist weights, and wider, heavier writing tools, such
as wide-grip pens.
Benabid et al.[[10]] reported that tremor suppression by stimulation directed to the VIM was maintained
over the long term (>2 years) and that such stimulation induced fewer adverse effects
such as dysarthria, disequilibrium, limb ataxia, dystonia, and paresthesias. Control
of these side effects is easily accomplished by reducing the intensity of the stimulator
or stopping stimulation altogether.[[8]],[[9]]
The physiological basis for VIM stimulation remains speculative, but the cerebellothalamic
pathways may play a significant role in the development of ETs.[[10]] Autonomous neuronal activities have been recorded in the VIM and these “tremor”
cells were found to have a bursting discharge pattern, with the burst frequency equal
to the patient's tremor frequency.[[8]] The VIM is considered to be a convergence point for both pallidal and cerebellar
afferent pathways.[[11]] The therapeutic mechanism of thalamic DBS may involve an alteration or functional
ablation of the firing center of the VIM or a desynchronization of overactive neurons
seen in ET.[[8]],[[9]] Stimulation could directly activate cells or axons by depolarization, but it could
also inactivate cells or axons by depolarization blockade.[[8]] Activation of cells could also have effects similar to inactivation by increasing
the release of inhibitory neurotransmitters such as γ-aminobutyric acid or by overriding
abnormally patterned burst activity.
Registration is recorded along one to five trajectories in the volume of interest
to identify the different structure boundaries. In general, these measurements are
performed in millimeter steps before reaching the target and often measurements even
go beyond the target structure. Most centers using microelectrode recording perform,
as well, intraoperative stimulation along the trajectory using the microelectrodes
stimulating in the micro-Ampere range,[[12]],[[13]] or macroelectrodes stimulating in the milli-Ampere range, for example, using radiofrequency
or DBS stimulation electrodes.[[14]],[[15]] In general, this is done at the same measurement points as for micro electrode
recording (MER), to evaluate the clinical effects with increasing stimulation voltage
and to determine symptom reduction and the clinical therapeutic and side effect thresholds
at each measurement point.
Staged surgery was performed in this female patient for two main reasons. One, extra
precaution was taken as the particular case was being performed for the first time
in the hospital. Second, the efficacy of VIM thalamic DBS needs to be ascertained
before going into the other side as the tremors were still present at rest. This patient
showed disabling resting and positional tremors and not intentional tremors. Her tremors
do not respond to medical therapy, and DaTscan did not show typical finding of Parkinson's
disease. Finally, her tremor was considered to be essential but not so typical. In
subthalamic nucleus DBS surgery, staged bilateral procedure had less adverse effect
than simultaneous one.[[16]]
Conclusion
We performed a VIM thalamotomy in a patient with bilateral ETs. Using semi-microelectrode
recordings, rhythmic discharges corresponding to the tremor rhythm were observed in
a wide area around the VIM nucleus of the thalamus, suggesting involvement of this
site in the tremors. The tremors resolved after coagulation of these thalamic neurons,
which was done in a staged fashion.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
