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1. Novel TMS for Stroke and depression (NoTSAD): Accelerated Repetitive
Transcranial Magnetic Stimulation as a Safe and Effective Treatment for
Post-stroke Depression
dr. Ashifa Maulidya Shibly
Supervisor :
dr. Afriani, Sp. S (K)

2. Contents
01
04
02
05
03
06
Introduction
Discussion Conclusion
Introduction Methods Results
Critical Appraisal

3. Introduction
01

4. Introduction
● Post-stroke Depression (PSD) is the most common neuropsychological
complication of stroke with prevalence of 33%
● Individuals with PSD are at a higher risk for suboptimal recovery, recurrent
vascular events, poor quality of life, and mortality
● Treatment of choice : Psychotherapy and Pharmacotherapy → Do not
respond → rTMS

5. Introduction
● The cause of PSD is likely multifactorial—with biological and psychosocial
components
● Evidence suggests that PSD has underlying biological causes and is not
merely a psychological response to new disability or a life-threatening
event

6. Pathophysiology
Lession Location
1. Left frontal lobe
2. Basal ganglia
3. Temporal lobe

7. 7

8. Pathophysiology
1. Inflammation hypothesis
2. Dysfunction of the HPA axis
3. Neurotropic hypothesis and
neuroplasticity

9. Treatment of Choice
Pharmacotherapy Psychotherapy
● SSRIs
(mirtazapine,
sertraline,
citalopram and
escitalopram
● SNRIs
● TCAs
● MAOIs
● NMDA blockers
● Nootropics
● CBT ● ECT
● tDCS
● rTMS
● VNS
Neuromodulation

10. Safety
Viabilty
Primary Outcome of this Study
Remission of Depression

11. Methods
02

12. ● All patients admitted to the inpatient stroke
service at tertiary comprehensive stroke
center between November 2018 - March 2019
● Acute hospitalization or follow up clinic visit
● Screened for depression with the Hamilton
Depression Rating Scale (HAMD-17)
Participants
Study Design ● Prospective open label pilot study
● without control group

13. ● Patient with radiographic evidence of ischemic stroke
● Within the last 2 weeks - 6 months following acute stroke
● From November 2018 - March 2019
N = 98 screened patients
fulfilled the inclusion criteria
62 Patients had logistical issues
and social situation
6 Patients successfully enrolled and completed the
stimulation protocol

14. Number of users analyzed in our market research

15. Procedure Timeline
Baseline Assessment :
● Modified rankin scale (mRS)
● Functional Independent
measures (FIM)
● NIHSS
● HAMD-17
● Mapping procedure and define RMT (Day 1)
● Coil placing → Dorsolateral prefrontal cortex (DLPFC)
● 20 Total stimulation sessions for 4 consecutive days
4 Days
Post treatment Assessment :
● mRS
● FIM
● NIHSS
● HAMD-17
● Adverse event
● mRS
● FIM
● NIHSS
● HAMD-17
● Adverse event
3 months
follow-up

16. Stimulation Protocol
● Neurostimulation was performed using Neurostar system 2.0 figure of eight coil
● First day : Mapping procedure and establishing Resting Motor Threshold (RMT)
● Coil was moved 5.5 cm anteriorly to the DLPFC
● High frequency (20 Hz) rTMS applied over the left DLPFC at 110% RMT for 5 sessions
per day (about 1 ½ hour), over 4 consecutive days → TOTAL 20 SESSIONS
● 40 trains of 2 second duration were applied with 12 second intertrain interval → Total
1,560 pulses per session
● Rest for 10-15 min between sessions

17. Statistical Analysis
Analysis using SAS 9.4
Alpha = 0.05
Variables
Categorical
Wilcoxon Signed rank test
McNemar’s exact test
Wilcoxon two-sample test with two-sided-t
approximation
Continuous
Ordinal and binary

18. Results
03

19. Baseline
characteristic
19

20. Outcome Measures
20
HAMD significantly decreased Pre and Post Stimulation (p = 0,03)

21. Outcome Measures
21
No statistically significant difference in FIM, mRS, or NIHSS

22. Depression Scores before and after rTMS
22
At 3-months
follow-up, 5 of 6
patients remained
non depressed, 1
patient score 8 at
the lowest end of
mild depression

23. Adverse event
23
1 subject described a headache milder than his usual chronic headache
1 subject experience transient facial sensitivity ipsilateral to the coil
Neither of these observations were rated bothersome

24. Discussion
04

25. The use of accelerated rTMS protocol PSD is safe and viable.
This high degree of tolerability is similar with previously published experience with
accelerated protocols.
rTMS is still the best at controlling frequency and location of stimulation,which offers
certain advantages
All treated patients experienced significant improvement, with 100% remission rate
directly following rTMS. Recent meta-analysis of 22 randomized controlled trials
indicated that rTMS is an effective tool to treat chronic PSD.

26. It is hypothesized that low frequency
TMS stimulates inhibitory neurons
while high frequency TMS stimulates
excitatory projection neurons, thus
mimicking neuroplasticity through
long-term potentiation

27. Low levels of peripheral and central Brain Derived Neurotropic Factor (BDNF) have
been observed in PSD
At a molecular level, findings from studies have shown that rTMS with excitatory
frequencies alters the expression of both the N-methyl-D-aspartate (NMDA) receptor
and the brain-derived neurotrophic factor (BDNF) genes and proteins, which are
excitatory neurotransmitters.
This supports the idea that rTMS plays a role in altering neuronal plasticity based on
gene expression

28. The novelty of this rTMS paradigm is the accelerated protocol as well as the
stimulation in the acute to subacute stroke period
Although this study was underpowered to demonstrate efficacy, the significant
remission rate is promising. Larger,randomized studies are needed to confirm
these results.
Study Limitations : Placebo effect, Small sample size, Self-selection bias

29. Conclussion
05

30. Accelerated rTMS is a safe and viable
treatment option for PSD in the subacute stroke population.
Depressive symptoms significantly improved in all treated
patients. Confirming these results in larger randomized settings
has the potential to establish accelerated rTMS as a potent
therapy for PSD

31. Critical Appraisal
06

32. Intervention
PICO
6 Patients with radiographic evidence
of ischemic stroke Within the last 2
weeks - 6 months following acute
stroke From November 2018 - March
2019
mRS, FIM, NIHSS, HAMD-17 Score and
Adverse event Before and after rTMS
sessions
High frequency (20 Hz) rTMS applied
over the left DLPFC at 110% RMT for 5
sessions per day (about 1 ½ hour),
over 4 consecutive days for total 20
sessions
Accelerated rTMS is a safe and viable
treatment option for PSD in the subacute
stroke population. Depressive symptoms
significantly improved in all treated
patients
Patients Comparison
Outcome

33. Study Validity

34. Importance
Are the result clinically/socially important?
Yes, this pilot study indicates that an accelerated rTMS protocol is a
safe and viable option, and may be an effective alternative adjunctive
therapy for patients suffering from PSD.
This preliminary findings can be a basis to conduct a larger randomized
study to establish accelerated rTMS as a potent therapy for PSD.

35. Applicability
The result of this study is applicable in our clinical practice.