Frameless and fiducial-less method for deep brain stimulation

Authors: D. Krahulík 1;  M. Nevrlý 2;  P. Otruba 2;  L. Hrabálek 1;  M. Vaverka 1;  P. Kaňovský 2
Authors‘ workplace: Department of Neurosurgery, University Hospital Olomouc 1;  Department of Neurology, University Hospital Olomouc 2
Published in: Cesk Slov Neurol N 2019; 115(3): 342-344
Category: Short Communication
doi: 10.14735/amcsnn2019342


Aim: Deep brain stimulation (DBS) is a very effective procedure for the treatment of idiopathic Parkinson‘s disease (PD), essential tremor and dystonia. The authors describe a method of DBS using frameless and fiducial-less system Nexframe (Medtronic), S8 navigation (Medtronic) and O-arm (Medtronic) for placing DBS electrodes in four patients (8 electrodes). To our knowledge, this is only the second centre in the world to have used this method.

Methods: Two adult patients with PD and two with essential tremor were indicated to bilateral DBS. Baseline neurological status and DBS-related improvement in motor function were measured using patients‘ diaries, Unified Parkinson‘s Disease Rating Scale and Clinical Global Improvement tests. The implantation of DBS leads was performed using MRI, preoperative CT examination and their fusion with perioperative O-arm imaging. The accuracy was checked using the same methodology as the Nexframe system. We also evaluated average time of surgery for Leksell frame-based surgery, Nexframe procedure and fiducial-less procedure.

Results: The accuracy and patient outcome were excellent, with a total error of 2.49 mm, without any complication. Average times of surgeries were: Leksell frame 290 min, Nexframe system 222 min and last procedure 201 min.

Conclusion: Implantation of DBS electrodes using frameless and fiducial-less system is a very useful and technically feasible procedure with excellent patient toleration. It will be necessary to operate in this way on many more patients to prove efficacy of this method, but from our point of view this method appears very promising


Parkinson’s disease – essential tremor – deep brain stimulation

Deep brain stimulation (DBS) is a widely used technique for modulation of subcortical brain structures in patients with Parkinson’s dis­ease (PD) [1,2], es­sential tremor [3], dystonia [4,5] and some other movement disorders. Class I evidence supports its use in PD, in comparison with best medical treatment [6]. The DBS is now be­­ing more frequently indicated also dur­­ing earlier stages of PD [7,8]. DBS electrodes have conventional­ly been placed us­­ing frame-based stereotaxy with micro-electrode record­­ing (MER) and physiological mapp­­ing of target structures. Frameless neuronavigation-guided implantation technique us­­ing skul­l-mounted aim­­ing devices: Nexframe© (Medtronic, Dublin, Ireland), STarFix© (FHC Inc., Bowdoin, ME, USA), Clearpoint© (MRI Interventions Inc., Irvine, CA, USA) is used in some centres in conjunction with bone-implanted fiducial markers. Hol­loway (Min­neapolis, USA) recently started to implant electrodes us­­ing the Nexframe© system without fiducials with peri­operative O-arm imaging. In this technique, brain images used for target­­ing CT and MRI are obtained preoperatively. The O-arm picture is taken at the begin­n­­ing of the surgical procedure and S8 plan­n­­ing software and navigation is used to register brain targets and plan­ned trajectories. The cor­rect position of electrodes is confirmed by micro recording, macrostimulation and perioperative O-arm control.


Four patients (eight electrodes) were implanted us­­ing the frameless and fiducial-less technique in October 2018. Two patients were treated for PD and the other two for tremor. PD patients met the Movement Disorder Society Clinical Dia­gnostic Criteria for Parkinson‘s Dis­ease [9] and patients treated for tremor had pharmacoresistant es­sential tremor. All patients were ful­ly informed about the procedure and the procedure was performed by a single surgeon (D. K.) and neurologists (M. N., P. O.)


Two MRI sets were obtained a few days before the surgery for PD patient: 1. volumetric 3D Gd-enhanced gradient echo MRI sequence cover­­ing the whole brain in 1 mm axial slices, mainly for trajectory plan­n­­ing and 2. T2 images turbo spin echo 2 mm slices for the borders of subthalamic nucleus (STN). For tremor patients, we used tracto­graphy and segmentation of thalamic nuclei accord­­ing to 1. high resolution inversion recovery T1 cover­­ing the whole brain and 2. dif­fusion tensor imag­­ing sequence: non-dif­fusion weighted data set, 30–60 dif­fusion gradient, as high a resolution as pos­sible.
CT scan cover­­ing whole head was obtained for the best fusion with perioperative O-arm
imaging (Medtronic, Dublin, Ireland).

Surgical technique

At the begin­n­­ing of the surgery, the 3D O-arm scan was obtained and fused with preoperative MRI and CT image in the S8 stereotactic navigation plan­n­­ing software (Medtronic). The target points for the tips of the electrodes were selected us­­ing a combination of direct (visualized) and indirect target­­ing in PD and with indirect target­­ing in tremor combined with MRI tractography and segmentation of thalamic nuclei. The trajectories were visualized on the volumetric MRI images us­­ing “navigation” views. Small adjustments were then made to avoid travers­­ing the cortical veins and dural venous lakes (easily seen on Gd-enhanced images) and lateral ventricles. Surgical procedures were car­ried out in two stages dur­­ing the same day. The first stage, implantation of the DBS electrodes was car­ried out on the patient whilst awake, and the second stage was implantation of the internal pulse generator, performed under general anaesthesia.

Us­­ing a pas­sive planar blunt probe and active S8 navigation, the burr hole entry point of the predetermined electrode trajectory was then marked on the skin, and a small hole was dril­led to mark that point on the skul­l. After we performed appropriate sterile preparation and draping, linear skin incisions were made, and burr holes centered on the pilot hole were completed. The lead anchor­­ing device (Stimlock©, Medtronic) and the Nexframe© base were attached to the skull and the navigated O-arm picture was taken and fused. The sterile registration was performed with target registration er­ror < 0.5 m­m. The Nexframe© tower was then attached and aligned to the cor­respond­­ing target us­­ing S8 navigation® software (Medtronic). Target depth was then calculated and set on the microTargetingTM Drive System position­­ing device. The dura was opened and closed by fibrin glue to prevent CSF leak or pneumocephalus (Fig. 1).

Intraoperative picture of navigated O-arm system.<br>
Obr. 1. Peroperační foto navigovaného systému O-arm.
1. Intraoperative picture of navigated O-arm system.
Obr. 1. Peroperační foto navigovaného systému O-arm.

Intraoperative microelectrode registration

To perform MER in STN-DBS, four MER/macrostimulation needles were placed in an ar­ray
with central, lateral, anterior and posterior to delineate the borders of the nucleus. A start­­ing point for the STN 10 mm above the MRI-based target was set and the microelectrodes were advanced in steps of 500 μm towards the target by an electric microdrive.

Macro-test stimulation

After MER, the tip of the microelectrode was retracted. Chan­nels that showed significant multi-unit activity over a length longer than 3 mm were selected for intraoperative test stimulation (60 μs pulse-duration; 130 Hz pulse frequency for PD and 145 Hz frequency for tremor). The complete electrode with the macro-tip was then advanced to be used for macro-test stimulation, and this was performed by an experienced neurologist (M. N., P. O.). After evaluat­­ing the selected chan­nels by macro-test stimulation, the one with the largest therapeutic window, i.e. the lowest cur­rent threshold for improvement of symp­toms and the highest threshold for side ef­fects, was chosen for permanent electrode implantation and the final control 3D O-arm scan was performed after insertion of final lead to confirm its accurate position. 3D O-arm scan can be used dur­­ing the surgery several times to confirm accurate position of the microelectrode or the lead. It takes just a few minutes to transfer pictures from O-arm into the plan­n­­ing station and to fuse images with CT and MRI. Final control of the position of the electrodes is managed by the Suretune© software (Medtronic) (Fig. 2).

Postoperative control of deep brain stimulation in the subthalamic
nucleus using the SureTune® software (Medtronic,
Dublin, Ireland).<br>
Obr. 2. Pooperační kontrola uložení elektrod hluboké mozkové
stimulace v subtalamickém jádru pomocí systému SureTune®
(Medtronic, Dublin, Irsko).
2. Postoperative control of deep brain stimulation in the subthalamic nucleus using the SureTune® software (Medtronic, Dublin, Ireland).
Obr. 2. Pooperační kontrola uložení elektrod hluboké mozkové stimulace v subtalamickém jádru pomocí systému SureTune® (Medtronic, Dublin, Irsko).

Lead anchoring and implantable pulse generator placement

Leads were anchored to the skull with a lead anchor­­ing device (Stimlock®, Medtronic). After scalp closure, the surgery continued under the general anaesthesia and the lead extenders and pulse generators were placed.


One month after surgery, all four patients had an excel­lent clinical outcome and there were no complications so far. Both tremor patients have improvement at Clinical Global Improvement scale + 3 (very much improved) and PD patients have 52% and 56%, respectively, reduction of OFF state and 59% and 53%, respectively, reduction of dopaminergic medication. The accuracy of this procedure was measured us­­ing the same methodology as the Nexframe© system [10]. The total er­ror was 2.49 mm (Tab. 1) and it is comparable with the Nexframe© and the frame-based systems [10].

1. Accuracy of the fiducial-less procedure.
Accuracy of the fiducial-less procedure.

We also evaluated average time of surgery in 129 patients treated with DBS in Olomouc. Average time for Leksell frame surgery (59 patients) was 290 min. DBS us­­ing Nexframe© system (66 patients) average time of surgery was 222 min and average time with the fiducial-less procedure (4 patients) was 201 min.


Deep brain stimulation is basical­ly performed by two methods, one us­­ing any stereotactic frame and the other us­­ing any frameless system with small fiducials attached to the skul­l. This new method excludes fiducials and uses perioperative O-arm imag­­ing and an online navigation system. None of the systems are strictly accurate and average er­ror is between 1–2 m­m. There are few weak points in the method that can lead to inaccuracy such as fusion between MRI, CT and O-arm, but the newest navigation system has an er­ror of about 1–2 imag­­ing voxels [11]. Urgosik et al analyzed accuracy of DBS placement us­­ing the Leksell frame accord­­ing to intraoperative monitor­­ing with very good results and minimum complications [12]. Rohlf­­ing et al found reduced accuracy of stereotactic frames because of torque introduced by the ef­fect of weight bear­­ing on the frame [13]. Krahulík et al and Hol­loway et al confirmed comparable accuracy of frameless systems to the frame-based systems [10,14].


Frameless and fiducial-less method us­­ing the Nexframe© system is an accurate and safe procedure and the best tolerated by our four patients. The total er­ror is not worse than with the Nexframe© system and frame-based systems and average surgery time for the fiducial-less procedure is shorter than with other methods used for the DBS procedure. It will be neces­sary for more patients to undergo this method in order to conclude its routine use.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Accepted for review: 16. 1. 2019

Accepted for print: 25. 3. 2019

doc. MUDr. David Krahulík, Ph.D., MBA

Neurochirurgická klinika

FN Olomouc

I. P. Pavlova 185/6, Nová ulice

779 00 Olomouc



1. Deuschl G, Paschen S, Witt K. Clinical outcome of deep brain stimulation for Parkinson‘s dis­ease. Handb Clin Neurol 2013; 116: 107–128. doi: 10.1016/B978-0-444-53497-2.00010-3.

2. Weaver FM, Fol­lett K, Stern M et al. Bilateral deep brain stimulation vs best medical ther­apy for patients with advanced Parkinson dis­ease: a randomized control­led trial. JAMA 2009; 301(1): 63–73. doi: 10.1001/jama.2008. 929.

3. Benabid AL, Pol­lak P, Gervason C et al. Long-term suppres­sion of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 1991; 337(8738): 403–406.

4. Kupsch A, Benecke R, Mül­ler J et al. Pal­lidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med 2006; 355(19): 1978–1990. doi: 10.1056/NEJMoa063618.

5. Vidailhet M, Vercueil L, Houeto JL et al. Bilateral deep-brain stimulation of the globus pal­lidus in primary generalized dystonia. N Engl J Med 2005; 352(5): 459–467. doi: 10.1056/NEJMoa042187.

6. Benabid AL, Chabardes S, Mitrofanis J et al. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson‘s dis­ease. Lancet Neurol 2009; 8(1): 67–81. doi: 10.1016/S1474-4422(08)70291-6.

7. Schüpbach WM, Rau J, Knudsen K et al. EARLYSTIM Study Group. Neurostimulation for Parkinson‘s dis­ease with early motor complications. N Engl J Med 2013; 368(7): 610–622. doi: 10.1056/NEJMoa1205 158.

8. Moro E, Schüpbach WM, Wächter T et al. Refer­­-
­r­­ing Parkinson‘s dis­ease patients for deep brain stimulation: a RAND/UCLA appropriateness study. J Neurol 2016; 263(1): 112–119. doi: 10.1007/s00415-015-7942-x.

9. Postuma RB, Berg D, Stern M et al. MDS clinical dia­g­nostic criteria for Parkinson‘s dis­ease. Mov Disord 2015; 30(12): 1591–1601. doi: 10.1002/mds.26424.

10. Krahulík D, Nevrlý M, Otruba P. Placement accuracy of DBS stimulation us­­ing the Nexframe system. Cesk Slov Neurol N 2017; 80/113(2): 208–212. doi: 10.14735/amcsn­n2017208.

11. Hemler PF, Sumanaweera TS, van den Elsen PA et al. A versatile system for multimodality image fusion. J Image Guid Surg 1995; 1(1): 35– 45. doi: 10.1002/ (SICI)1522-712X(1995)1:1<35::AID-IGS6>3.0.CO;2-N.

12. Urgošík D, Jech R, Růžička E. Hluboká mozková stimulace u nemocných s extrapyramidovými poruchami pohybu – stereotaktická procedura a intraoperační nálezy. Cesk Slov Neurol N 2011; 74/107(2): 175–186.

13. Rohlf­­ing T, Maurer CR Jr, Dean D et al. Ef­fect of chang­­ing patient position from supine to prone on the accuracy of a Brown-Roberts-Wel­ls stereotactic head frame system. Neurosurgery 2003; 52(3): 610–618.

14. Hol­loway KL, Gaede SE, Starr PA et al. Frameless stereotaxy us­­ing bone fiducial markers for deep brain stimulation. J Neurosurg 2005; 103(3): 404–413. doi: 10.3171/jns.2005.103.3.0404.

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