TMS in Neurosurgery-An emerging

tool to MODULATE brain

Dr R PHANIRAJ
Consultant Neurosurgeon
Renova Institute of Neurological sciences
RENOVA HOSPITALS
Hyderabad
 What is a “successful” Neurosurgery?
• The goal of any Neurosurgery is
– Complete removal or treatment of the pathology
with minimal complications.
– Reduction or resolution of symptoms- pain or a
neurological deficits.
– Minimal surgical complications like infection,
bleeding, or neurological damage.
– Early regain of function and return to daily
activities.
– Long-term improvements in quality of life and
functional independence.
 How is it achieved?
• Technique and technology
– Experienced Surgical Team
– Thorough Surgical Planning and mapping critical structures
– Neuroimaging Technologies: advances in CT/MRI/DTI
– Advanced Surgical Techniques robotic/ minimally
invasive/Endoscopic methods
– Real-time navigation guidance and Intraoperative
Monitoring.
– Tumor fluorescence/ICG/Intra op Neurophysiological
Testing
– Advanced Neurorehabilitation
 Focus of rehabilitation
• Advanced neurorehabilitation for improved
outcome
– modulating neural activity.

– focused on promoting neuroplasticity, encourage

the brain to adapt and reorganize in response to
injury.

– enhanced motor recovery and cognitive function

• Transcranial magnetic stimulation is one such
emerging tool which can have impact in
diagnosis, planning and execution of
Neurosurgical procedures and potent adjunct
in effective neuromodulation thereby
resulting in early recovery from debilitating
neurodeficits.
 Applications of rTMS in Neurosurgery

• Preoperative Planning:
– Mapping Brain Function: identify and map eloquent areas
of the brain responsible for motor, sensory, and language
functions.
• Postoperative Recovery:
– Enhancing Recovery: by promoting neuroplasticity and
aiding in the rehabilitation of cognitive and motor
functions.
• Pain Management:
– rTMS has shown promise in managing postoperative pain,
particularly in patients with chronic pain syndromes.
 Principle
• Magnetic Field Generation:
– When an electric current flows through the coil, it
creates a magnetic field that penetrates the skull
without causing discomfort.
• Induction of Electrical Currents:
– The magnetic field induces electrical currents in the
underlying cortical neurons.
• Modulation of Neuronal Activity:
– The induced currents can either excite or inhibit
neuronal firing, depending on the frequency of the
stimulation.
– High frequency stimulation (>5Hz) is exitatory and low
frequency stimulation(1Hz) is inhibitory.
• Neuroplasticity:
– rTMS promotes neuroplasticity, the brain's ability to
reorganize and form new neural connections by
stimulating specific brain areas.
• Neurotransmitter Release:
– influence the release of neurotransmitters, such as
dopamine, serotonin, and glutamate which can help
improve mood, cognition, and motor function.
 What is a pulse
• A "pulse" refers to a single magnetic stimulation delivered to the brain.
– generates a brief magnetic field that induces an electric current leading to changes in neuronal activity.
• Types of Pulses:
• Single Pulses:
– evokes immediate sensory or motor responses and can therefore help assess the efficacy or speed of
conduction of a particular neural pathway
• Repetitive Pulses:
– rTMS involves delivering multiple pulses in quick succession, typically at a defined frequency. The most
common frequencies include:
• High-Frequency (≥5 Hz): Often used to enhance excitability in the targeted brain area. This is common in treating
conditions like depression.
• Low-Frequency (≤1 Hz): Used to inhibit activity in overactive brain regions, which can be beneficial in conditions like
chronic pain.
• Burst Stimulation:
– Pulses are delivered in short bursts rather than continuous stimulation. This can combine the effects of
high and low frequencies and may improve efficacy for certain conditions.
• Theta Burst Stimulation (TBS):
– A form of rTMS that delivers bursts of pulses at high frequency (usually 50 Hz) in a patterned manner
(e.g., 3 pulses every 200 ms). TBS is thought to induce longer-lasting effects and is often used in research
and clinical settings.
 Where to stimulate
• Dorsolateral Prefrontal Cortex (DLPFC):
– Application: Primarily targeted for treating depression and anxiety disorders.
– Function: Involved in executive functions, mood regulation, and cognitive processes.
• Motor Cortex:
– Application: Used in rehabilitation for stroke patients and to treat motor disorders like
Parkinson’s disease.
– Function: Controls voluntary movements; stimulating this area can help improve motor
function and reduce spasticity.
• Primary Sensory Cortex:
– Application: Targeted for pain management, particularly in chronic pain syndromes.
– Function: Processes sensory information; modulation can help alleviate pain perception.
• Anterior Cingulate Cortex (ACC):
– Application: Used for mood disorders and chronic pain management.
– Function: Involved in emotional regulation, decision-making, and impulse control.
• Temporoparietal Junction (TPJ):
– Application: Investigated for treating conditions like schizophrenia and improving social
cognition.
Neurosurgical Applications
 Preoperative mapping
• Maximal resection of pathologic lesions while preserving
the surrounding eloquent brain
• Traditional theories regarding discrete brain regions
housing critical functions and the general functional
topography of the brain have been challenged
• architecture-distorting lesions pose additional
challenges for determining eloquent vs. non-eloquent
brain.
• nTMS involves the use of non-invasive, image-guided
stimulation of the brain to generate a functional map
that differentiates eloquent from non-eloquent tissue
• It is reported that nTMS not just affects indication and planning in surgery but also results in a higher rate of gross total
resection and a lower rate of surgery-related paresis
• Krieg compared the surgical outcome of patients with motor eloquent metastatic lesions who received preoperative
nTMS-based motor mapping with those that did not. Patients receiving nTMS had a lower rate of residual tumor, smaller
craniotomies, shorter operation time, and decreased surgery-related paresis [53]. Krieg comprehensively studied the
impact of preoperative motor mapping by nTMS on different clinical outcome parameters within a homogeneous cohort
of high-grade glioma patients. The results demonstrated that patients who underwent nTMS preoperative mapping had
smaller craniotomies and less residual tumor tissues [54]
• Picht used nTMS in a group of patients with gliomas and found nTMS mapping could change the therapy planning into
early and more extensive resection. The median change of tumor volume from baseline to 1 year was − 83% in the nTMS
group, but + 12% in the comparison group
• Functional mapping with nTMS is available not only in tumorous brain lesions, but also within hypervascularized cortical
areas
• Many studies had shown that nTMS can serve as a powerful tool to schedule planning prior to surgery for patients with
arteriovenous malformation and cavernous angiomas, and it can also help optimize treatment planning
• The mapping based on nTMS can visualize the language network more efficiently and can also detect cortical plasticity
induced by an intra-hemispheric tumor-induced cortical plasticity. It can be used to formulate a tailored surgical plan
which could preserve language function after the surgery. This tool could play a supplementary role for neurosurgeons in
dealing with patients with potential language-eloquent tumors, but not applicable for awake surgery
• Besides surgical planning, the nTMS data and nTMS-based tractography are far beyond its current application.
• Schwendner implemented nTMS motor mapping in patients with intracranial metastases during routine radiotherapy.
• The results showed that it can significantly reduce the dose applied to the motor cortex while not affecting the treatment
doses for the planning target volume
• TMS can be applied to precisely targeted brain regions using commercially available
frameless stereotactic techniques.
• Furthermore, the generated electrical field can be modulated based on magnetic
pulse waveform, frequency of stimulation, pattern of stimulation, as well as variables
such as the orientation of the current lines induced in the brain and excitable neural
elements
• These elements permit tailored, patient-specific stimulation paradigms.
• Three types of general TMS protocols exist, including single-pulse, paired pulse, and
repetitive TMS (rTMS)
• In particular, rTMS is used to facilitate excitation or inhibition of cortical areas and is
often used in research related to treatment modalities.
• In rTMS, multiple single-pulse stimuli are delivered at a specified time duration,
frequency, and intensity with effects varying according to stimulation parameters [4].
• Slow rTMS, for example at 1 Hz or one magnetic pulse per second, has
demonstrated inhibitory effects.
• In comparison, fast rTMS at 10 or 20 Hz, has demonstrated excitatory effects
 technique
• Single pulse TMS (sTMS) (1).
• Repetitive TMS (rTMS) modulates brain function in such
a way that effects last beyond the period of stimulation.
The magnetic and electrical fields generated by rTMS
bring about many changes in the human brain that may
confer therapeutic benefit (2). For instance, since rTMS
can have lasting effects on cortical excitability through
induced synaptic plasticity mechanisms, it is likely to help
in the treatment of various psychiatric and CNS disorders
where cortical excitability is one of the primary
underlying pathologies (1, 2, 6, 8, 13).
 applications
• Post TBI
• Post tumor surgery
• Post stroke
• Chronic pain syndromes
• Trigeminal neuralgia
• nTMS in mapping
• Movement disorders
• Cognitive disorders
•
rTMS stimulation to induce plastic changes at the language motor area
in a patient with a left recidivant brain tumor affecting Broca's area
• Juan A. Barcia
• ,Ana Sanz
• ,Mercedes González-Hidalgo
• ,Carmen de las Heras
• ,Pedro Alonso-Lera
• ,Pedro Díaz
• , show all
• Pages 132-138 | Received 12 Jul 2010, Accepted 13 Dec 2010, Published
online: 25 Jul 2011
Post TBI
 Tumor surgery
• Tumor surgeries particularly when involving eloquent regions,
carries a risk of neurologic complications
• Deficits may result due to
– surgical damage to critical cortical and subcortical pathways
– vascular injury
– disruption of critical network connections involved in complex
neurologic functions.
• rTMS helps map eloquent regions involved in motor and speech
function preoperatively.
• guide intraoperative identification.
• preservation of these functional pathways.
• limited evidence for rTMS neurorehabilitation for
motor and speech deficits acquired post-
operatively in patients with brain tumors. Given
the efficacy in stroke, investigations into the
potential of targeted rTMS to improve post-
operative outcomes in brain tumor patients has
been pursued with promising results [26, 27]. We
reviewed the current literature for data involving
post-operative rTMS use for neurorehabilitation.
• Techniques varied with studies using frameless stereotactic
navigation for targeting.
• stimulation protocols varied, but mostly involved contralateral
inhibitory stimulation of the primary motor cortex for motor
rehabilitation.
• Most commonly, a frequency of 1-5 Hz and an intensity of 80-90%
of motor threshold was utilized in conjunction with intense physical
therapy and rehabilitation.
• Studies varied widely on the timeframe of initiating TMS
postoperatively, but most studies prescribed a course of rTMS once
daily for between 5 to 22days
• post-operative rTMS was shown to be safe, less side effects, no
effect on wound healing, no documented instance of seizure
• rTMS in post-operative neuro-oncology
patients did demonstrate benefits for both
language and motor recovery.
• Overall data demonstrate a rate of 90%
reported improvement of some motor or
language function.
• Target- contralateral inhibitory TBS protocol
for treatment of motor deficits, where rTMS
was applied to the unaffected hemisphere.
 Chronic pain Syndromes
• rTMS is a cortical stimulation technique that has been applied to modulate abnormal
brain activities to alleviate pain.
• The mechanism of cortical stimulation for pain relief is based on the modification of
neuronal excitability.
• rTMS is postulated to induce alterations in the activity of cortical and subcortical brain
structures that are related to pain modulation and processing, including the
orbitofrontal cortices, medial thalamus, anterior cingulate, and periaqueductal gray
matter
• Additionally, rTMS reduces chronic pain by triggering descending inhibitory neural
pathways to act at the dorsal-horn level
• Specifically, rTMS is known to alter neuronal activities in the periaqueductal gray matter,
which is related to pain processing
• Stimulation frequency is associated with synaptic changes; higher frequencies (> 5 Hz)
are excitatory, and lower frequencies (< 1 Hz) are inhibitory.
• , high-frequency stimulation increases cortical excitability, while low-frequency
stimulation decreases cortical excitability The stimulation frequency can be applied
differently according to the stimulation site and patient pain conditions.
 Trigeminal and other Neuralgias
• navigated high frequency rTMS targeted on the
functional primary face motor area may be effective and
safe for chronic facial pain with a 40% response rate
• cumulative effect of repeated 5-days rTMS treatments
separated by 6 weeks.
• The first treatment was able to potentiate the effect of
the second treatment.
• The 10Hz protocol was more effective when
administered after the 20Hz treatment, as if the 20Hz has
a priming effect.
epilepsy
Movement disorders
 Post stroke rehabilitation
• TMS protocols for post-stroke neurorehabilitation typically involve a
patterned protocol known as theta burst stimulation (TBS), which has
demonstrated relatively few adverse effects as compared to more
conventional rTMS protocols
• These protocols are further divided into either delivering low-
frequency, inhibitory TBS to the contralateral hemisphere (continuous
TBS; cTBS) or high-frequency, stimulatory TBS to the ipsilateral affected
hemisphere (intermittent TBS; iTBS)
• Data from these studies have suggested that downregulation of
excitability of the intact or contralateral hemisphere by using TBS
results in improvements in paresis, language, attention, memory, and
somatosensory processing when combined with physical rehabilitation
• ipsilateral excitatory TBS has also been demonstrated to improve motor
recovery
Precautions
Results
scope