1st nbs workshop abstracts

Abstracts from the

1st. International Workshop

on Navigated Brain

Stimulation in Neurosurgery

October 10-11, 2009, Berlin, Germany

Organized by Dr. Th. Picht and PD Dr. O. Suess

Department of Neurosurgery,

Charité - Universitätsmedizin Berlin, Berlin, Germany

Workshop supported by Nexstim Oy

1st International Workshop on Navigated Brain Stimulation in Neurosurgery

Published: March 1st, 2010 Page | 1

List of Abstracts

Introduction .................................................................................................................... 2

Principles of Navigated Brain Stimulation ......................................................................... 3

Nexstim Oy, Helsinki, Finland

nTMS, DCS and fMRI: perioperative assessment in central region tumours ........................ 5

Hospital of the Johann Wolfgang Goethe University, Frankfurt am Main, Germany

DCS in intraoperative cortical mapping ............................................................................. 7


Navigated Brain Stimulation in motor cortex tumour surgery ............................................ 8

Charité – Universitätsmedizin Berlin, Berlin, Germany

Navigated Brain Stimulation (NBS) mapping of the motor strip prior to epilepsy and glioma

surgery .......................................................................................................................... 10

Kuopio University Hospital, Kuopio, Finland

NBS-MEG mapping in epilepsy surgery ........................................................................... 12

Helsinki University Central Hospital, Finland

Navigated Brain Stimulation in pediatric epilepsy: a case study ....................................... 13


Peritumoral mapping with NBS and fMRI ........................................................................ 14

Sahlgrenska University Hospital, Göteborg, Sweden

Extra-intracranial bypass surgery in chronic haemodynamic ischemia ............................. 15


NBS-determined resting motor threshold in chronic haemodynamic cerebral ischemia .... 16

Charité - Universitätsmedizin Berlin, Berlin Germany

Motor cortex stimulation and NBS in pain therapy .......................................................... 18

Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France



Introduction to the 1st International Workshop on Navigated

Brain Stimulation in Neurosurgery

It is now generally accepted that the optimal approach to the treatment of many brain pathologies

requires the assessment of the functional significance of the adjacent cortical structures.

Direct electrical cortical stimulation (DCS) is a well-established technique for the examination of

cortical function during surgery. Until now, however, we have lacked a reliable method for assessing

cortical function without first performing craniotomy. Functional imaging studies like fMRI, which

rely on measuring hemodynamic changes as a presumed consequence of task paradigms, have their

shortcomings in the vicinity of rolandic tumors with altered local vasculature.

The recently introduced NBS System (Nexstim Oy, Finland), is an approach which combines two well-

understood technologies, 3D spatial image navigation and transcranial magnetic stimulation (TMS),

into a novel, non-invasive system which is accurate and reliable and allows for functional mapping of

the cortex in both research and clinical use.

The goal of the 1st International Workshop on Navigated Brain Stimulation (NBS) in Neurosurgery in

Berlin was to share the experiences of experts in NBS, TMS and DCS with a wider audience. To

further that goal, the presenters agreed to make abstracts and images from their presentations

available also to colleagues unable to attend the workshop in person. Many of the presentations

contained previously unpublished data and we are profoundly grateful for authors’ permission to

publish their abstracts in this collective format. The workshop program covered:

Functional anatomy and neurophysiology with TMS/DCS

Technical background of Navigated Brain Stimulation (NBS)

Presurgical mapping in brain tumour and epilepsy

NBS in chronic cerebral ischemia and stroke

NBS in chronic pain therapy

While preparing the 2nd International Workshop on Navigated Brain Stimulation in Neurosurgery to

be held in Berlin, 2010, the NBS System was cleared by the Food and Drug Administration (FDA) for

sale and marketing in the USA. We will therefore also be able to invite our colleagues from the USA

to join us and make the next workshop even more international than the first where colleagues from

15 countries took part.

The organizers,

Dr. Th. Picht and PD Dr. O. Suess

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany

2010, February 26



Principles of Navigated Brain Stimulation

Jarmo Ruohonen, PhD; Henri Hannula, MSc; Tuomas Neuvonen, MSc; Jari Karhu, MD; Jarmo Laine,

MD

Nexstim Oy, Helsinki, Finland

Figure 1. TMS coil locations recorded in the examination session (left). The stimulus E-field

maximum locations within the brain were calculated and colour-coded according to the

corresponding peak-to-peak MEP amplitudes as a heat map, with the locations eliciting the largest

MEPs colour-coded white (middle). Enlarged image (right).

Figure 2. The motor representation area data (left) can be stored in DICOM-formatted files for

export to a surgical neuronavigator. NBS mapping results displayed on a StealthStation® Navigation

System (Medtronic, Minneapolis, MN, USA) (right).

Transcranial magnetic stimulation (TMS) is an established method to generate pulses of electric field

(E-field) inside the brain strong enough to activate cortical neurons. Stimuli that exceed the motor

threshold will activate neurons and propagate the activation along neuronal pathways to other parts

of the brain and to the periphery. Stimulation of the cortical motor representation area of the

thumb abductor muscle will thus activate the corresponding part of the motor pathway and, finally,

the thumb muscle.



Navigated Brain Stimulation (NBS System, Nexstim Oy, Finland) is an image-guided method for

accurately predicting and visualizing the area of the cortex activated by the TMS E-field. Visualization

and guidance are achieved by combining patient MRI data and information provided by the optical

tracking system which links the stimulation coil with respect to the head. Motor activation is

measured using integrated electromyography (EMG) from surface electrodes placed over muscles of

interest. System software links together the brain anatomy (MRI-data), the location of the TMS E-

field (navigation) and the motor-evoked potential (MEP) responses. Results are presented as maps,

showing the cortical representation areas of individual muscles in detail. NBS can also be used to

guide repetitive TMS (rTMS) for diagnostics and therapy. In presurgical mapping, preliminary

experiences suggest that NBS with rTMS can be used to identify motor areas in the cortex needed

for speech production.

Cortical mapping with NBS has been successfully applied in cases of partial and complete paresis,

including cases where the anatomy has been unclear or smeared by tumour, oedema or

cerebrovascular changes. NBS has also been used to map functional reorganization of the motor

cortex after neurosurgery. Cortical mapping with the NBS System has been well tolerated in clinical

use and no adverse events have been recorded.

Conclusion

Targeting TMS with visualized E-field makes NBS is an accurate and reliable diagnostic technique for

mapping the eloquent cortex. Unlike fMRI, NBS mapping is not dependent on the patient’s

willingness or ability to participate in tasks and is not confounded by haemodynamic changes or

anatomical changes due to prior surgery. NBS represents a new standard for non-invasive clinical

work-up prior to resection of lesions close to the central region of the cortex.



nTMS, DCS and fMRI: perioperative assessment in central

region tumours Andrea Szelényi, MD PhD1, Marie-Terese Forster, MD1, Elke Hattingen, MD PhD2

1Department for Neurosurgery,

2Department for Neuroradiology, Hospital of the Johann Wolfgang Goethe University,

Frankfurt am Main, Germany

Introduction

In cerebral tumour surgery, the recent change of treatment paradigm includes a more aggressive

surgical approach, as there is increasing evidence that the amount of tumour resection correlates

with the recurrent free survival time. Despite the desire of the largest resection possible, the

postoperative well-being and unchanged neurological status of the patient is precept. To achieve

such an aim in tumours adjacent to the motor cortex, precise preoperative planning and intra-

operative assessment of the motor area is essential.

Thus we compared the preoperative motor cortex mapping results of fMRI and navigated

transcranial magnetic stimulation (nTMS) with the maps created by independently performed direct

electrocortical stimulation (DCS).

Methods

fMRI The MRI studies were performed on a 3 Tesla Magnetom Allegra Scanner (Siemens Medical

Solutions, Erlangen, Germany). Structural 3-dimensional isovolumetric T1-weighted data were

acquired using a magnetization-prepared rapid-acquisition gradient echo (MPRAGE) sequence.

Functional MRI was performed in a block design experiment using a blood oxygenation level-

dependent (BOLD)-sensitive echo planar imaging (EPI) sequence. The patients performed a simple

visually guided motor task. Mapping data was only collected for patients able to perform the tasks.

nTMS nTMS was performed with the NBS System (Nexstim Oy, Finland). After determining the hot spot for

the ID1 muscle by a figure-of-8 coil, the motor threshold (MT) was set according to the Awiszus

protocol. Mapping was further performed at 110% of MT. Individual 3D anatomical MRI data sets

with superimposed fMRI data were integrated in the NBS workstation. Each spot was stimulated

twice; the data was analyzed post-hoc and used to create a response map for each individual

muscle. MEPs were recorded from the ID1 muscle, additional muscles were chosen according to the

tumour location and included the biceps brachii, extensor digitorum communis, thenar, anterior

tibial, abductor hallucis and orbicularis oris muscles.

DCS Intra-operatively, motor cortex mapping was performed with DCS using a monopolar anodal probe

(2mm diameter). Stimulation parameters consisted of a train of five pulses with an individual pulse

width of 500 ms and an inter-stimulus interval of 2 ms. The maximum intensity was limited to 25

mA. During surgery, the coordinates of each DCS site were unambiguously defined and integrated

into the neuronavigation system. A post-hoc comparison of the coordinates of nTMS, fMRI and DCS

was performed.



Data analysis

Intra-operatively, the preoperative mapping results were not displayed on the neuronavigation

system. The surgeon was therefore blinded towards the nTMS results while performing DCS. fMRI

mapping data were first imported into the NBS System. To compare DCS with NBS and fMRI, all data

were entered post-operatively into a Stealth Station® Neuronavigation System (Medtronic,

Minneapolis, MN, USA) for analysis.

Results

Preliminary results from 11 patients (fMRI data were obtained in 10 patients) are presented. The

mean distance between the NBS hotspots and the DCS hotspots was 9 mm, the mean distance

between the centres of fMRI activity and the DCS hotspots was 16 mm.

Conclusion

Using NBS, nTMS results are closer to monopolar DCS results than fMRI and, taking into account all

error sources, the agreement between nTMS and DCS results is as close as one can practically

achieve. nTMS seems to be a powerful method for preoperative planning as well as providing

preoperative estimation of direct cortical stimulation locations. With nTMS, the decision to perform

surgery on a patient previously not considered for resection can be made, and straightforward

surgical planning can be achieved.

Case presentation: Peritumoral mapping with NBS. No fMRI data available from M1 areas close to

the tumour margin.



DCS in intraoperative cortical mapping Prof. Dr. med. Theodoros Kombos

Charité-Universitätsmedizin Berlin, Berlin, Germany

Intraoperative, invasive direct cortical stimulation (DCS) has a high success rate, with 98% ability to

determine the primary motor cortex. There are two different techniques for direct electrocortical

stimulation: bipolar and monopolar. Despite the term monopolar, two electrodes are required but

there is a large distance between the active and ground electrodes.

In the monopolar technique, the stimulating current penetrates the underlying tissue deeper and

more focally than in the bipolar technique. In clinical practice bipolar stimulation therefore has a

pronounced cortical effect, whereas monopolar stimulation recruits more sub cortical components.

In DCS, it cannot be assumed that an action potential happens directly under a specific electrode,

since current is applied to a circuit full of connections and it is impossible to determine or control

where the current is spreading. At high stimulation currents the cerebrospinal fluid also acts as a

conductor, further spreading the effect of the stimulation current.

With monopolar stimulation it is possible to distinguish between the hand or the upper arm or the

leg muscles, but it is impossible to delineate cortical representation areas corresponding to

individual muscles in practice. In bipolar stimulation, motor area differentiation is not as good as

with the monopolar technique. Bipolar DCS stimulates the whole extremity and representation area

accuracy is therefore less precise than in monopolar.

With the monopolar technique, no risk of seizures has been shown. In contrast, the bipolar

technique incurs a significant risk of seizures, occurring in up to 30% of cases. Seizures can also be

difficult to differentiate from anticipated stimulation response, as whole extremities can be

innervated by bipolar DCS.

Conclusion

DCS is an established intraoperative cortical mapping methodology. Monopolar DCS has a

pronounced subcortical effect, whereas bipolar stimulation has a broader cortical effect. Monopolar

is a more accurate technique than bipolar. However, bipolar allows mapping of the premotor frontal

cortex. Due to the current spreading mechanisms inherent to DCS, even the monopolar technique

cannot reproduce the kind of individual muscle representation area differentiation presented in

studies with Navigated Brain Stimulation (NBS System, Nexstim Oy, Finland).



Navigated Brain Stimulation in motor cortex tumour surgery Picht T, Frey D, Schmidt S, Brandt S, Vajkoczy P, Suess O

Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Berlin, Germany

Navigated brain stimulation (NBS) is a new method for presurgical analysis of cortical function. Like

the gold-standard of direct cortical stimulation, it maps cortical function by stimulation rather than

imaging, yet it has the benefit of doing so non-invasively. The aim of the present study was to

evaluate the accuracy of a new 3D-MRI-navigated TMS system (NBS System, Nexstim Oy, Finland)

and its usefulness in motor cortex tumour surgery.

Figure 1. Presurgical mapping with NBS (left) and intra-operative DCS (right).

The motor areas of 35 patients with distorted cortical anatomy due to tumours of the primary motor

cortex, as well as two cases of supplementary motor area (SMA) lesions, were mapped

preoperatively with NBS. The results were transferred to the neuronavigator and implemented for

planning and performance of the tumour resection. Sixteen of these 35 patients were mapped intra-

operatively with navigated direct cortical stimulation (DCS). The stimulus locations eliciting the

largest EMG response in the target muscles (“hot spots”) were determined for each method and

compared. The impact of the preoperative NBS results on the surgical strategy was categorized for

all cases.

A detailed peritumoral motor cartography could be established in all cases. For the 16 cases where

both NBS and DCS results were available, the median (range) distance between the hot spots of NBS

and DCS in respect to the abductor pollicis brevis muscle was 7.47 (0.83 – 15.59) mm.



The NBS results influenced the surgical strategy in 15 of 35 cases (43%): in 13 cases the surgical

approach was adapted, in two cases the indication for surgery was revised. In the two cases of SMA

lesions, NBS identified direct corticospinal tracts in the immediate vicinity of the lesions. Both

patients suffered from transient functional worsening postoperatively.

In addition to clarification of the cortical anatomy, the motor excitability in terms of resting motor

threshold (RMT) was also taken into account. In patients with severe paresis a RMT within normal

range seems to be an indicator for possible functional recovery after tumour resection. Vice versa,

an unusually high RMT in a patient without paresis seems to indicate an elevated risk for paresis

caused by surgery.

NBS can delineate distinct cortical muscle representation with a high degree of accuracy, even in

cases of severely distorted anatomy, and also in cases where tumours are located in the SMA region.

Moreover, NBS can also help specify individual prognosis in terms of motor function by evaluation of

the motor excitability.



Navigated Brain Stimulation (NBS) mapping of the motor strip

prior to epilepsy and glioma surgery Juha E. Jääskeläinen, MD, PhD, Professor and Chairman

Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland

A total of 22 patients considered for extratemporal lesional epilepsy surgery or supratentorial glioma

(grade II-IV) surgery were studied preoperatively with navigated TMS (NBS System, Nexstim Oy,

Finland) to map the eloquent motor cortical areas. In the epilepsy group (11 patients), 10 patients

underwent lesional epilepsy surgery, 3 of the operations were re-operations. In the glioma group (11

patients), all patients had surgery, 2 of them were re-operations.

In the epilepsy group, 8 of the 10 patients undergoing surgery were seizure-free (Engel I) post-

operatively with no permanent deficits. In the 11 patients operated on for gliomas, 3 had temporary

mild motor weakness and 4 had temporary mild speech deficits, but there were no permanent

deficits. The NBS mapping retained its reliability, in particular, in the patients having had previous

surgery, despite changed neurovascular architectures.

In the 11 epilepsy surgery patients mapped with NBS, no definite enhancement of epileptiform

activity occurred on EEG during the TMS sessions. Two patients exhibited their typical interictal

epileptiform abnormalities, and one patient had a habitual seizure some minutes after TMS. There

was no discomfort reported in the epilepsy patient group. In the 11 glioma patients, there were no

TMS-related changes in online EEG. One glioma patient reported pain at two stimulation sites in the

previous operative area, and one patient was restless. Lack of induced epileptiform activity in the

epilepsy patients suggests that the single-pulse technique may not help to disclose epileptogenic

areas.

Figure 1: Orange dots above a

glioblastoma represent the primary

motor area eliciting EMG responses

to NBS stimulation. Courtesy: NBS

Group, Clinical Neurophysiology,

Kuopio University Hospital.



Conclusions

1. Motor strip mapping with NBS is equivalent to the direct electrocortical stimulation mapping

through subdural grid electrodes or during surgery.

2. NBS is unaffected by neurovascular perfusion abnormalities, and is a reliable technique for motor

mapping also in areas of previous surgeries.

3. NBS helps to identify the limits of microsurgical removal of diffuse grade II-IV gliomas, i.e., the

eloquent structures of the brain.

4. NBS seems to be well-tolerated and safe for epilepsy patients with intractable extratemporal

lesional epilepsy.

5. The NBS technique should be evaluated comprehensively in the localization of epileptogenic

cortical areas



NBS-MEG mapping in epilepsy surgery J.P Mäkelä, A-M. Vitikainen , P. Lioumis

BioMag Laboratory, HUSLAB, Helsinki University Central Hospital, Finland

Patients presenting for epilepsy surgery with epileptic foci close to eloquent cortical areas benefit

from accurate identification of the epileptogenic zone and the irretrievable cortex. Presently,

electrical cortical stimulation (ECS) via subdural grid electrodes is the standard procedure despite

the risks associated with diagnostic surgery.

We have employed a multimodal preoperative approach for localization of the epileptogenic and

sensorimotor cortical regions, adding two non-invasive techniques to the normal work-up. Navigated

transcranial magnetic stimulation using the NBS System (Nexstim Oy, Finland) was used to

determine the location of the motor cortical representation areas and magnetoencephalography

(MEG; Elekta Neuromag Oy, Finland) was used to determine the somatosensory cortex and the ictal

onset zones. The results from these two non-invasive methods were used as supplement for

planning subdural grid placement and later compared with the results from ECS via subdural grids,

and validated by surgical outcome.

The results from NBS and MEG were consistent with the results from ECS. NBS provided improved

spatial precision compared to ECS in some patients (Vitikainen et al. 2009). NBS mapping provided

information about the extent of cortical motor representation areas, not easily available in MEG.

NBS mapping, applying single-pulse TMS close to the motor threshold, did not elicit epileptiform or

ictal EEG activity even when stimulated sites overlapped MRI- localized epileptogenic region (Figure).

Seizures were often elicited during ECS. Our preliminary results also suggest that NBS can be used to

locate language-related cortical regions.

Conclusion: NBS and MEG can be added to the preoperative work-up and may even hold a potential

to replace invasive ECS in a subgroup of epilepsy patients with a suspected epileptogenic zone near

the sensorimotor cortex and seizures frequent enough for ictal MEG.

Figure 1: Result of motor mapping with NBS in

a patient with epilepsy. A indicates anterior, L

left, R right. Hand, arm and foot muscle motor

representations follow crude somatotopy. Light

brown dots at the vertex indicate stimulation

sites overlying the epileptiform region. No

seizures were elicited by nTMS. Data from

Vitikainen et al. (2009).

Reference: Vitikainen A-M, Lioumis P, Paetau R, Salli E, Komssi S.

Metsähonkala L, Paetau A, Kičid D, Blomstedt G, Valanne, L,

Mäkelä JP, Gaily E: Combined use of non-invasive techniques for

improved functional localization for a selected group of epilepsy

surgery candidates. NeuroImage 45, 342-348, 2009.



Navigated Brain Stimulation in pediatric epilepsy: a case study Sein Schmidt, Stephan A. Brandt

Clinic of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany

An 8-year-old male patient with a history of encephalitis and focal epileptic seizures from the age of

four was referred for a surgical evaluation. Prior to treatment with multiple anti-epileptic drugs, the

boy had experienced sensory aurae and focal epileptic seizures of left temporal lobe origin up to 20

times per day, as well as daily grand mal seizures. Although he no longer had generalized seizures,

the patient still experienced 5 to 10 focal seizures per week.

New MR images were taken immediately prior to non-invasive mapping of the motor cortex by

navigated brain stimulation (NBS) using an NBS System (Nexstim Oy, Finland). No pathological

structures were visible on the new MR images. Cortical excitability was significantly affected by the

three anti-epileptic drugs taken by the patient. At 110% of motor threshold (MT), NBS elicited MEPs

at only one location on the unaffected hemisphere. On the affected hemisphere, NBS elicited MEPs

at multiple locations after the stimulation intensity was reduced by at least 44%.

Subsequently, structural Mr images taken three years earlier became available. The earlier images

showed a transient diffusion restriction in the same sensorimotor locations where NBS was now able

to elicit MEPs. Post-hoc, the earlier images provided validation of a pathology which could be elicited

by NBS, but was not visible on the current structural MR images, and could not be detected by fMRI

or other imaging techniques available. Further, NBS was able to induce sensory aurae in the patient

at a location which was in concordance with the location of the pathological structure visible in the

earlier MR images. The presurgical work-up revealed that the epileptogenic area was intricately

linked to the motor and somatosensory cortex. The boy was not recommended for resection due to

the evident risk of permanent hemiparesis, and a non-surgical therapy solution was found.

Conclusion

For the presurgical localization of epileptic foci with structural origin, MRI, PET and SPECT are useful

imaging techniques. This patient case suggests that NBS might play a role, together with other

imaging modalities, in the non-invasive presurgical localization of epileptic foci in patients without

structural lesions or in patients with transient pathologies. Further research is warranted to show

whether NBS may offer a non-invasive alternative to intraoperative localization methods using

subdural electrodes or extraoperative corticography.



Peritumoral mapping with NBS and fMRI Magnus Thordstein1, MD, PhD, Göran Pegenius1 , BMT, Simon Bergstrand1, MSc, Håkan Olausson1 ,

MD, PhD, Bertil Rydenhag2, MD, PhD, Mikael Elam1 , MD, PhD

Dep. of Clinical Neurophysiology1 and Neurosurgery

2, Sahlgrenska University Hospital, Göteborg, Sweden

The clinical utility of navigated transcranial magnetic stimulation (TMS) for preoperative mapping of

cortical motor areas was studied and compared to the utility of functional magnetic resonance

imaging (fMRI). Five patients with cerebral lesions in locations with a potential risk for motor

function deficit following surgical resection were studied. Mapping was performed with a Navigated

Brain Stimulation (NBS) system (NBS System, Nexstim Oy, Finland) using the patient’s structural MR

image as the basis for navigation. Electromyography (EMG) responses were recorded from hand,

arm, leg and face muscles using surface EMG electrodes.

In all patients, both the NBS and fMRI techniques identified cortical representation areas from

where the motor activity presumably originated. Compared to fMRI, more areas of the primary

motor cortex could be investigated using NBS. There was reasonably good spatial agreement

between the two techniques. However, preliminary comparison of finger tapping fMRI images fused

with NBS mapping results suggest that NBS and fMRI are not measuring the same physiological

phenomenon. One 18-year-old male epilepsy patient presenting for a re-operation had a seizure

during fMRI. There were no adverse events during NBS mapping.

Conclusion: NBS appears to be a promising new tool for preoperative mapping of cortical motor

areas, generating information which may be difficult to obtain from other methods. NBS mapping is

safe and well tolerated, and all patients studied preferred their experience of NBS mapping to their

fMRI study.

Figure 1: Preoperative

investigation in a 16-year-old

boy with therapy-resistant

epilepsy caused by left-sided

cavernoma. Fused image

from structural MR, fMRI

(finger tapping of the

contralateral hand) and NBS

mapping of primary motor

cortex. Note that the location

of the volume of maximal

fMRI activation is deeper and

posterior to the hand motor

area defined with NBS.



Extra-intracranial bypass surgery in chronic haemodynamic

ischemia Professor Dr. Peter Vajkoczy, MD, Director of Dept.


Extra-intracranial bypass surgery has regained significant relevance over the past few years. The aim

of this presentation is to highlight the current indications and recent developments in this field.

One main indication today is stroke prevention by flow augmentation in the setting of chronic

cerebral haemodynamic ischemia, which is defined as a combination of steno-occlusive

cerebrovascular disease, inadequate collateralization and loss of cerebrovascular reserve capacity.

Another indication is flow replacement in the context of therapy of complex aneurysms and skull

base tumours.

The herein proposed revival of bypass surgery is due to progress in individualized, tailored

therapeutic strategies as well as patient selection. Furthermore, we have witnessed a dramatic

improvement in surgical technique as well as the development of a broad armamentarium of

different bypass types, which today allow tailored revascularization strategies for our patients.

Finally, the revival of bypass surgery is also explained by the dramatically reduced risk of

perioperative ischemia due to significant technical progress in bypass surgery. Our future work is

focused on further refining the selection and characterization of patients suffering from chronic

haemodynamic ischemia, as well as furthering the understanding of the pathophysiology of this

cerebrovascular impairment. Extra-intracranial bypass surgery has become a central part of a highly-

specialized, interdisciplinary strategy for the therapy of chronic haemodynamic ischemia, complex

aneurysms and skull base tumours.

Angiography of an extra-intracranial bypass (STA-MCA)



NBS-determined resting motor threshold in chronic

haemodynamic cerebral ischemia Jussen, D.


The evaluation of cerebrovascular reserve capacity (CVRC) helps identify risk of stroke in patients

with internal carotid artery (ICA) or middle cerebral artery stenosis/occlusion and stratification of

patients for surgical treatment. Cerebral blood flow below the normal range (50-100 ml/100g/min) is

associated with increasing functional impairment and the risk of cerebral infarction. The incidence of

stroke is significantly higher in patients with reduced CVRC.

CVRC can be measured with the help of different technological methods and administration of

intravenous acetazolamide, a cerebral vasodilator, which causes an increase of cerebral perfusion.

Loss of CVRC means absence of increase of cerebral perfusion. Measurement of CVRC allows

estimation of the degree of haemodynamic stenosis. All methods previously used to evaluate CVRC

(transcranial doppler sonography, SPECT, PET, xenon-CT and perfusion MRI) have been based solely

on the measurement of perfusion.

We hypothesize that resting motor threshold (RMT), reflecting cortical excitability, is a clinically

useful functional measurement reflecting the effect of chronic cerebral ischemia at a metabolic

level. RMT, elicited by TMS from muscle representation areas, is elevated in patients with chronic

haemodynamic ischemia, resulting in significant interhemispheric differences in RMT between the

affected and unaffected hemispheres. The aim of our study is to assess the role of RMT as a

functional marker of chronic haemodynamic ischemia in patients without manifest stroke.

Inclusion criteria for the study are: recurrent transitory ischemic attacks (TIA) or minor strokes, no

ischemic changes or border zone infarctions visible on MRI, high-grade stenosis or occlusion of the

ICA or the middle cerebral artery (MCA) and reduced CVRC. Patients were divided into two groups,

patients with atherosclerotic stenosis of the arteries supplying the brain and patients with

Moyamoya disease.

RMT and CVRC measurements were performed preoperatively and post-operatively at 5 days and 3

months. RMT was measured from the maximal representation area of the FDI muscle in both

hemispheres with navigated TMS (NBS System, Nexstim Oy, Finland). CVRC was estimated from

SPECT in the baseline state and after stimulation with 1g of acetazolamide (DiamoxR).

Case 1: 58-year-old female patient presented with occlusion in the right ICA and history of TIA with

transient left-sided hemiparesis. MRI showed only lacunar infarction in both hemispheres.

Angiography showed occlusion of the right ICA. Loss of CVRC detected via SPECT and Diamox

indicated diminished perfusion on the right side. Right hemisphere RMT was 75 V/m compared to

unaffected left hemisphere RMT of38 V/m. At the time of RMT measurement with NBS, the patient

experienced latent left-sided hemiparesis.

Case 2: 38-year-old female patient with Moyamoya disease scheduled for EC-IC bypass. The patient

had a history of TIA with transient hemiparesis on the left side. At the time of RMT measurement



with NBS the patient had no motor deficit. Loss of CVRC detected via SPECT and Diamox indicated

diminished perfusion on the right side preoperatively. Right hemisphere RMT was 63 V/m compared

to unaffected left hemisphere RMT of 40 V/m. At 5-days post-operatively, there were no significant

changes in RMTs, right hemisphere RMT was 61 V/m compared to left hemisphere RMT of 39 V/m.

At 3 months postoperatively, there were significant balancing in RMTs with right hemisphere RMT at

40 V/m compared to unaffected left hemisphere RMT of 41 V/m.

Conclusion

In chronic haemodynamic cerebral ischemia, EC-IC bypass surgery improves the circulatory and

metabolic situation and facilitates adaptive reorganization via higher cortical excitability. Cortical

excitability in the affected hemisphere improves after successful EC-IC bypass surgery.

Interhemispheric differences in RMT, reflecting differential cortical excitability, can be measured and

monitored by NBS. The correlation between clinical outcomes and post-operative changes in

interhemispheric RMT and changes of cortical excitability deserves further evaluation in surgical

treatment of chronic cerebral ischemia.

Figure 1: Angiography of an ICA occlusion right (top left). MRI of lacunar infarction on both sides (top

right). NBS-determined RMT (bottom left). SPECT with Diamox showing diminuished perfusion right

(bottom right).



Motor cortex stimulation and NBS in pain therapy Prof. Jean-Pascal Lefaucheur, MD, PhD

Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil,

France

Stimulation of the primary motor cortex using surgically-implanted epidural electrodes has been

demonstrated to be a therapeutic option for patients with severe, intractable neuropathic pain.

Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex at high frequency, a non-

invasive cortical stimulation strategy, has also been shown to induce significant analgesia in patients

with chronic neuropathic pain. The effects provided by rTMS are short-lasting, but more prolonged

pain relief (up to several weeks) can be obtained by administering daily rTMS sessions for several

days. The analgesic effect of epidural motor cortex stimulation is presumed to be produced by

cathodal stimulation of horizontal fibres, tangential to the cortical surface, located in the precentral

gyrus. The mechanisms of action for invasive epidural stimulation and non-invasive rTMS are likely to

be very close. Therefore, orientation of the cortical fibres relative to the orientation of the

stimulation coil can also determine the therapeutic effect of rTMS on pain: rTMS effect does not

differ from sham condition in case of lateromedial coil orientation, whereas turning the coil to

posteroanterior axis produces significant pain relief, at the same site of cortical stimulation. MRI-

image based navigation of the TMS coil greatly facilitates the correct orientation of the TMS-

generated E-field in the individual patient’s gyrus, especially during a 30-minute session of

stimulation and between the sessions in case of repeated sessions for treatment.

Motor cortex stimulation acts on various aspects of chronic pain (sensori-discriminative, affective-

emotional) differentially between patients. Factors not predictive for the outcome of surgically-

implanted motor cortex stimulation include the type or localization of the lesion at the origin of pain,

the duration of disease, motor function in pain region and sensory status. Conversely, the response

to rTMS sessions could be a valuable predictive factor of therapeutic response to subsequent

surgical motor cortex stimulator implantation. The use of MRI-guided navigation system could also

help to export the coordinates of a cortical target, validated by the clinical response to rTMS

sessions, to the operating room for surgical electrode implantation.

Conclusion

Clinical results using a dedicated MRI-guided navigation system to deliver rTMS therapy (NBS

System, Nexstim Oy, Finland) suggest that the pain relief obtained by rTMS correlates with the pain

relief achieved by subsequent surgical procedures. However, absence of rTMS efficacy is not a

predictor of negative outcome for surgical implantation. In the management of chronic pain, the

positive predictive value of rTMS may play a useful role in the selection of patients for epidural

electrode implantation. Although the role of rTMS as a clinical tool in chronic pain may be limited by

the short duration of the induced effects, rTMS has been shown to have a clinical therapeutic impact

in patients with transient pain syndromes. However, all these applications of rTMS in the pain

domain still deserve further research.



Workshop supported by:

Nexstim Oy, Elimäenkatu 9 B, FI-00510 Helsinki, Finland Phone +358-9-2727-1710. Fax +358-9-2727-1717 www.nexstim.com

1st nbs workshop abstracts

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