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Letters to the EditorNeurosurgical Forum

J Neurosurg Volume 123 • July 2015 289

J Neurosurg 123:289–296, 2015

Trigeminal neuralgiaTO THE EDITOR: We are very interested in the arti-

cle by Monteith et al.1 (Monteith SJ, Medel R, Kassell NF, et al: Transcranial magnetic resonance–guided focused ultrasound surgery for trigeminal neuralgia: a cadaveric and laboratory feasibility study. J Neurosurg 118:319–328, February 2013). Trigeminal neuralgia often induces severe pain and impairs quality of life, even with multi-modal therapies. The trigeminal pain often results from offending artery compression to the trigeminal nerve. Monteith et al.1 performed a laboratory investigation in cadaveric specimens to clarify the feasibility of transcra-nial MR-guided focused ultrasound therapy for trigeminal neuralgia. They found that real-time MR thermometry demonstrated the heating effect of focused ultrasound on the trigeminal nerve with 10°C increments in temperature. Moreover, the heating effect may collaterally spread to the internal acoustic canal (IAC).

Their study provided solid evidence that MR-guided focused ultrasound surgery (MRgFUS) is capable of in-creasing focal heating of up to 18°C in the trigeminal nerve of a cadaveric specimen at the root entry zone. Im-portantly, MRgFUS did not produce a significant heating effect on the skull base and surrounding neural structures in no-pass regions. However, there are some minor con-cerns. First, MRgFUS cannot avoid an off-target effect producing a local temperature effect on adjacent crucial neurovascular structures, such as the brainstem and cra-nial nerves, as the authors observed with the vestibular nerve in the region of the IAC. Their study leads read-ers to ask about the damaging heating effects on vascular structures, which can induce thrombus formation and lead to ischemic injury of the brainstem. Their study delivered results in cadaveric human specimens, but not in living animal models. Therefore, the pain reduction effect still cannot be estimated from their study. We fully agree that in vivo studies are warranted to ensure the safety and ef-ficacy of MRgFUS in treating trigeminal neuralgia.

Zhi-Hong Zheng, MDYi Lin, MD

Pin-Shuo Su, MDPeng-Wei Wang, MD

Wei-Ting Tsai, MDDueng-Yuan Hueng, MD, PhD

Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

DiScLoSurE The authors report no conflict of interest.

reference 1. Monteith SJ, Medel R, Kassell NF, Wintermark M, Eames

M, Snell J, et al: Transcranial magnetic resonance–guided focused ultrasound surgery for trigeminal neuralgia: a cadaveric and laboratory feasibility study. J Neurosurg 118:319–328, 2013

responseWe greatly appreciate the thoughtful comments from

Dr. Zheng and colleagues. In our study, we investigated the potential use of transcranial MRgFUS treatment for trigeminal neuralgia. As Zheng et al. point out, there is concern regarding the collateral heating of adjacent struc-tures, namely surrounding bone of the acoustic canal. In-deed, it was this concern that prompted specific design aspects of our investigation and the development of strate-gies to minimize these potential heating effects. From in vivo experimentation in swine4 and the results of thermal lesioning in the ventral intermediate nucleus of the thala-mus in humans for the treatment of essential tremor,1 we have learned much in terms of local temperature effects. The lesion size is highly reproducible with an extremely sharp gradient between normal and necrotic tissue that is similar to that in other thermal lesioning modalities, such as radiofrequency, and is probably even more distinct than the gradient produced from ionizing radiation.4 This sharp lesion drop-off means that there is no damage to surround-ing brain parenchyma. Experience in 30 patients treated for chronic pain and movement disorders, as described by Jeanmonod et al., confirms this sharp drop-off in a le-sion created by FUS.2,3 No cases of thrombus formation or stroke in the region surrounding the lesion, as determined by diffusion-weighted imaging, were reported.

In trigeminal neuralgia, larger vessels near the trigemi-nal nerve would not be directly targeted, and this sharp en-ergy drop-off would be utilized to target the nerve distant to the vascular structure. In addition, the heat-sink effect from rapid vascular flow helps defray heating of the ves-sel. It should also be noted that in the setting of trigeminal neuralgia, a higher “lesional” temperature—as currently utilized in FUS lesioning procedures for pain and move-ment disorders—would not be used since the goal is not to cause necrosis of the entire nerve, but to demyelinate and interrupt the pain fibers only.

Concern regarding the IAC is valid and was of particu-lar interest in these experiments. The geometry of the re-

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quired positioning of the ultrasound transducer to target the trigeminal nerve is such that the ultrasound “shadow” falls onto the IAC. Bony absorption of ultrasound energy and subsequent heat generation were significantly miti-gated by turning off transducer elements pointing at the IAC. Further optimization of this process will continue to address this issue and improve this collateral heating.

We agree with Zheng et al. as regards the determina-tion of the pain-relieving effect. The cadaveric targeting model is clearly not helpful in determining this. Given the subjective nature of pain and the complex nature of trigeminal neuralgia, we suspect that a clinical trial is re-quired to determine efficacy. Intraoperative assessments of the therapeutic effect following sequential increases in temperature application to the nerve, similar in tech-nique to that performed with radiofrequency rhizotomy, may be a reasonable paradigm to follow. In vivo studies of somatosensory evoked potential signal attenuation and histological analysis of cranial nerves in animal models of FUS may be of some value in parameter optimization prior to a clinical trial.

Stephen J. Monteith, MDW. Jeff Elias, MD

University of Virginia Health System, Charlottesville, VA

references 1. Elias J, Huss D, Loomba J, Khaled M, Frysinger R, Sperling

S, et al: A phase 1 study of MR-Guided focused ultrasound thalamotomy for the treatment of medication-refractory essential tremor. Presented at the current and Future ap-plications of Focused ultrasound 2012, 3rd international symposium, Washington, DC, 2012 (Abstract) (http://www.fusfoundation.org/images/pdf/FUSF_Symposium_2012_ Program_WebVersion.pdf) [Accessed March 27, 2015]

2. Jeanmonod D, Moser D, Magara A, Kowalski M, Bühler R, Pourtehrani P, et al: Study on incisionless transcranial magnetic resonance-guided focused ultrasound treatment of neuropathic pain: safety, accuracy and clinical outcomes. Presented at the current and Future applications of Focused ultrasound 2012, 3rd international symposium, Washington, DC, 2012 (Abstract) (http://www.fusfoundation.org/images/pdf/FUSF_Symposium_2012_Program_Web Version.pdf) [Accessed March 27, 2015]

3. Jeanmonod D, Werner B, Morel A, Michels L, Zadicario E, Schiff G, et al: Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thala-motomy for chronic neuropathic pain. Neurosurg Focus 32(1):E1, 2012

4. Khaled M, Hilliard J, Frysinger R, Sheehan J, Wintermark M, Lopes MB, et al: A Magnetic resonance imaging and his-tological comparison of focused ultrasound, radiofrequency, and Gamma Knife radiosurgery lesions in swine thalamus. Presented at the current and Future applications of Focused ultrasound 2012, 3rd international symposium, Washington, DC, 2012 (Abstract) (http://www.fusfoundation.org/images/pdf/FUSF_Symposium_2012_Program_Web Version.pdf) [Accessed March 27, 2015]

iNcLuDE WHEN ciTiNg Published online May 8, 2015; DOI: 10.3171/2012.11.JNS122202.©AANS, 2015

Diagnostic strategy in patients with subarachnoid hemorrhage

TO THE EDITOR: With interest I read the article by Delgado Almandoz et al.2 about the diagnostic yield of CT angiography (CTA) and MR angiography (MRA) in an-giographically negative subarachnoid hemorrhage (SAH) (Delgado Almandoz JE, Jagadeesan BD, Refai D, et al: Diagnostic yield of computed tomography angiography and magnetic resonance angiography in patients with ca-theter angiography–negative subarachnoid hemorrhage. J Neurosurg 117:309–315, August 2012). Computed tomog-raphy angiography demonstrated a cerebral aneurysm in 4 (9.3%) of 43 patients with aneurysmal SAH. Magnetic resonance angiography demonstrated only 1 of these an-eurysms. No causative cerebral aneurysms were found in patients with perimesencephalic SAH or CSF xanthochro-mia. Three of these 4 aneurysms were, in retrospect, visi-ble on angiography but were not recognized or interpreted as the cause of SAH.

In another article about the same patient group,3 diag-nostic yield of repeat catheter angiography was assessed in patients with SAH and negative catheter angiography and CTA. The first repeat catheter angiography performed 7 days after presentation demonstrated a causative vascular abnormality in 3 (4.4%) of 68 patients, 2 with aneurysmal SAH and 1 with perimesencephalic SAH. The second re-peat catheter angiogram obtained in 43 patients (59.7%) did not demonstrate any causative vascular abnormali-ties. In this scenario, a patient with an SAH without an aneurysm eventually undergoes 3 catheter angiography sessions, a CTA, and a MRA to confirm that there is no aneurysm.

This study again demonstrates that aneurysms can be missed fairly easily on catheter angiography as well as on CTA and MRA. This is not surprising since all 3 imaging modalities are no longer the best way to detect an aneu-rysm. In the late 1990s 3D rotational angiography became available for clinical practice. This technique has evolved into a quick and easy to perform procedure. In our hospi-tal we have used 3D angiography as a primary imaging tool in patients with aneurysmal SAH for more than a de-cade (we reserve CTA for patients with perimesencephalic SAH only). A rotational run takes 6 seconds with manual injections of 12–18 ml of contrast material, which is much quicker and cheaper than a multiple projection 2D angio-gram with 10 ml of contrast per projection. Reconstruc-tion of the 3D images takes a few seconds.

In various studies we demonstrated the superior image quality and diagnostic yield of 3D angiography in com-parison to 2D angiography. In 19 (83%) of 23 patients with aneurysmal SAH and negative 2D catheter angiography, 3D angiography demonstrated an aneurysm as the cause of SAH.5 Of 94 additional aneurysms detected with 3D angiography in 350 patients with a target aneurysm, 27 (29%) were missed on 2D angiography.6 Perhaps the best demonstration of the superior image quality of 3D angi-ography is in the detection of fenestrations in cerebral ar-teries in almost 40% of patients; most of these anomalies were, even in retrospect, not visible on 2D angiography.1,7

J Neurosurg Volume 123 • July 2015290



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An SAH is a serious disease, and the patient has the right to a quick and definitive diagnosis followed by treat-ment. We use the following imaging strategy: CTA is used as the exclusive imaging modality in patients with a perimesencephalic SAH pattern to exclude a basilar tip aneurysm. These patients have the same low a priori chance of an aneurysm as every other healthy individu-al (1%–2%). In patients with aneurysmal SAH, we start with 3D angiography studies of all vessels. In cooperative patients this is done under local anesthesia, and when an aneurysm that can be coiled is detected, we immediately proceed with the induction of general anesthesia followed by coiling. In uncooperative or intubated patients we per-form 3D angiography directly under general anesthesia, and when possible, the aneurysm is coiled. When no aneu-rysm is found on 3D angiography studies of all vessels, we do not routinely repeat the angiography but do so only on a case-by-case basis, for example, in young patients. Mag-netic resonance angiography is reserved for the follow-up of coiled aneurysms only4 and has no place in the setting of acute SAH.

As Delgado Almandoz et al. rightly point out, the most important drawback of their study is “the lack of rotational angiography with 3D reconstructions in the initial catheter angiogram in all patients.” There is a simple solution to this problem: use 3D angiography more liberally.

Willem Jan van rooij, PhDSt. Elisabeth Ziekenhuis, Tilburg, The Netherlands

DiScLoSurE The author reports no conflict of interest.

references 1. de Gast AN, van Rooij WJ, Sluzewski M: Fenestrations of the

anterior communicating artery: incidence on 3D angiography and relationship to aneurysms. aJNr am J Neuroradiol 29:296–298, 2008

2. Delgado Almandoz JE, Jagadeesan BD, Refai D, Moran CJ, Cross DT III, Chicoine MR, et al: Diagnostic yield of computed tomography angiography and magnetic resonance angiography in patients with catheter angiography–negative subarachnoid hemorrhage. J Neurosurg 117:309–315, 2012

3. Delgado Almandoz JE, Jagadeesan BD, Refai D, Moran CJ, Cross DT III, Chicoine MR, et al: Diagnostic yield of repeat catheter angiography in patients with catheter and computed tomography angiography negative subarachnoid hemorrhage. Neurosurgery 70:1135–1142, 2012

4. Majoie CB, Sprengers ME, van Rooij WJ, Lavini C, Sluzew-ski M, van Rijn JC, et al: MR angiography at 3T versus digital subtraction angiography in the follow-up of intracra-nial aneurysms treated with detachable coils. aJNr am J Neuroradiol 26:1349–1356, 2005

5. van Rooij WJ, Peluso JP, Sluzewski M, Beute GN: Additional value of 3D rotational angiography in angiographically nega-tive aneurysmal subarachnoid hemorrhage: how negative is negative? aJNr am J Neuroradiol 29:962–966, 2008

6. van Rooij WJ, Sprengers ME, de Gast AN, Peluso JP, Slu-zewski M: 3D rotational angiography: the new gold standard in the detection of additional intracranial aneurysms. aJNr am J Neuroradiol 29:976–979, 2008

7. van Rooij SB, van Rooij WJ, Sluzewski M, Sprengers ME: Fenestrations of intracranial arteries detected with 3D rotational angiography. aJNr am J Neuroradiol 30:1347–1350, 2009

responseNo response was received from the authors of the origi-

nal article.


correlation of diffusion tensor imaging and intraoperative macrostimulation

TO THE EDITOR: We read with great interest the pa-per by Said et al.9 (Said N, Elias WJ, Raghavan P, et al: Cor-relation of diffusion tensor tractography and intraoperative macrostimulation during deep brain stimulation for Par-kinson disease. J Neurosurg 121:929–935, October 2014). On deeper inspection we find that the conclusions drawn from the results of this work are based on scientific meth-ods that are not consistent with the current state-of-the-art methods in the burgeoning field of “connectomic neuro-surgery.”6 It is our belief that the authors’ conclusions need to be put into a more explicit context. 1) There cannot be a direct correlation between voltage (U) amplitude (applied during macrostimulation in deep brain stimulation [DBS] surgery) and the distance to the medial corticospinal tract (CST). There is some correlation that might be found be-tween stimulation current (I) and distance,8 as we have used in subthalamic nucleus surgery previously.4 However, according to Ohm’s law (I = U/R), resistance (tissue im-pedance and others = R) needs to be correlation-evaluated. This in itself is difficult, and there might be ways to bring impedance, electrode geometry, and stimulation voltage into perspective in an attempt to draw conclusions on the distance to the medial CST border.2,3,7 In the currently per-formed fashion, a pure correlation between voltage and distance is not the most relevant measure. 2) The rendition of the CST with the diffusion tensor imaging (DTI) tech-nology as shown in this work (Fig. 2) is not constructed using state-of-the-art methods and underestimates the spa-tial distribution of the pathway in the subthalamic region. This has implications for the measurements and, in turn, for the definition of the medial border of the CST, which are known limitations of deterministic tractography in this application.7 However, we agree that it is difficult to cor-rectly judge the size and shape of the internal capsule and explicitly define the medial border of the CST on a patient-specific basis under any circumstances. This issue is com-pounded by the diversity of tracking algorithms that are available to the surgeon by commercial software systems, albeit not originally designed for this purpose, but rather to provide a gross estimate of structural connectivity.1 3) The inherent desire to trust software that the user may not fully understand represents a dangerous proposition when sub-sequently used for scientific analysis or clinical decision support, exemplified in Fig. 1 of Said et al.’s article, which depicts the CST in the wrong anatomical location relative to the patient anatomy (i.e., it should have been recognized




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on simple visual inspection that the CST should be situ-ated lateral to the DBS electrode).

Several groups around the world, including both of our groups, are researching the application of diffusion-weighted imaging and tractography technology for the use in planning and performing DBS surgery in its various indications.5,10 We have shown in our previous work that tractography can be applied with a high enough accuracy to directly assist DBS surgery. It is not our intention to sup-press results that might contradict our own work. However, conclusions should be based on proper scientific methods, and these should be debated openly. Our analysis suggests that this study represents an attempt to apply advanced imaging concepts with typical clinical imaging data sets whose collection were likely not appropriately designed for such a purpose, coupled with the use of overly simpli-fied “push button” tractography provided in commercial software. We propose that an important basic goal for our field should be to establish a best-practices approach to preoperative MRI data collection and tractography analy-sis for future studies, for example, definition of minimum resolutions and signal-to-noise ratios for imaging data sets worthy of inclusion in scientific publications, as well as consensus-based identification of the most accurate and robust tractography metrics, specifically designed for the task at hand.

Volker A. coenen, MD Freiburg University Medical Center, Freiburg, Germany

cameron c. Mcintyre, PhD Case Western Reserve University, Cleveland, OH

DiScLoSurE Dr. Coenen has been a consultant for Medtronic and is a consultant for Precisis AG and received research support from Medtronic Europe and Boston Scientific. Dr. McIntyre reports that he is a consultant for Boston Scientific Neuromodulation and Surgical Information Sciences.

references 1. Bürgel U, Mädler B, Honey CR, Thron A, Gilsbach J, Coenen

VA: Fiber tracking with distinct software tools results in a clear diversity in anatomical fiber tract portrayal. cen eur Neurosurg 70:27–35, 2009

2. Butson CR, Maks CB, McIntyre CC: Sources and effects of electrode impedance during deep brain stimulation. clin Neurophysiol 117:447–454, 2006

3. Chaturvedi A, Butson CR, Lempka SF, Cooper SE, McIntyre CC: Patient-specific models of deep brain stimulation: influ-ence of field model complexity on neural activation predic-tions. Brain stimul 3:65–67, 2010

4. Coenen VA, Fromm C, Kronenbürger M, Rohde I, Reinacher PC, Becker R, et al: Electrophysiological proof of diffusion-weighted imaging-derived depiction of the deep-seated pyramidal tract in human. Zentralbl Neurochir 67:117–122, 2006

5. Coenen VA, Schlaepfer TE, Allert N, Madler B: Diffusion tensor imaging and neuromodulation: DTI as key technology for deep brain stimulation. int rev Neurobiol 107:207–234, 2012

6. Henderson JM: “Connectomic surgery”: diffusion tensor im-aging (DTI) tractography as a targeting modality for surgical modulation of neural networks. Front integr Neurosci 6:15, 2012

7. Mädler B, Coenen VA: Explaining clinical effects of deep brain stimulation through simplified target-specific modeling

of the volume of activated tissue. aJNr am J Neuroradiol 33:1072–1080, 2012

8. Ranck JB Jr: Which elements are excited in electrical stimu-lation of mammalian central nervous system: a review. Brain res 98:417–440, 1975

9. Said N, Elias WJ, Raghavan P, Cupino A, Tustison N, Frysinger R, et al: Correlation of diffusion tensor tractogra-phy and intraoperative macrostimulation during deep brain stimulation for Parkinson disease. J Neurosurg 121:929–935, 2014

10. Sweet JA, Walter BL, Gunalan K, Chaturvedi A, McIntyre CC, Miller JP: Fiber tractography of the axonal pathways linking the basal ganglia and cerebellum in Parkinson dis-ease: implications for targeting in deep brain stimulation. J Neurosurg 120:988–996, 2014

responseWe thank Drs. Coenen and McIntyre for sharing their

thoughts about our article. We must admit that we too were surprised by the negative results of our study, as we are also believers in the potential of DTI and advanced neu-roimaging in general. However, we thought it important to publish these negative results to warn the neurosurgical community about the pitfalls of a simplistic application of DTI to neurosurgical guidance. As demonstrated by our results, the traditional macrostimulation in DBS surgery cannot be merely replaced by measuring a distance from electrodes to tracts on DTI. There are multiple reasons for this, including some related to physiology and physics, or others related to the variation in terms of the shape and size of the CST in individual patients. Another important source of potential error in the clinical setting is the di-versity of DTI acquisition techniques and DTI processing algorithms. These multiple methods cannot be considered as being interchangeable, and the degree of specializa-tion required to master the DTI technology challenges the widespread, safe utilization of DTI for neuronavigation in individual patients. Definitions of best practices are a desired goal, but they are extremely difficult to achieve considering the number of stakeholders involved (imag-ing manufacturers, processing software companies, users, and regulatory authorities). An easier alternative is for in-dividual institutions to develop their expertise in the spe-cific DTI tool that they select and to develop a detailed understanding of the strengths, limitations, and pitfalls of this tool.

Max Wintermark, MDW. Jeff Elias, MD

University of Virginia Health System, Charlottesville, VA


Nickel allergy and aneurysm clipsTO THE EDITOR: In the article by Tan et al.3 (Tan T,

Tee JW, Han TF: Cell-mediated allergy to cerebral aneu-rysm clip causing extensive cerebral edema. J Neurosurg




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121:924–928, October 2014), the authors highlight the first case of vasogenic cerebral edema caused by a cell-mediated hypersensitivity reaction 4 years after aneurysm clipping in a 60-year-old woman with a history of severe nickel contact dermatitis. They discuss the possibility of nickel hypersensitivity, speculating that the intermittent nature of their patient’s cerebral edema may have resulted from the sporadic leaching of nickel from the Phynox clip. This then produced the cycle of acute-on-chronic cell-mediated hypersensitivity response that was visualized on imaging studies.

In contrast with their findings of an acute-chronic cy-cle of hypersensitivity reaction in a patient with a known nickel allergy, we recently reported on an acute case in a 33-year-old woman who developed a life-threatening al-lergic vasculitis following clipping of her brain aneurysm several weeks earlier with a nickel-containing clip.1 Our patient progressively declined, facing deteriorating clini-cal status (i.e., seizures) and additional infarctions. Re-peatedly, neither she nor her family affirmed any contact dermatitis or nickel allergy. Finally, during decompressive surgery, biopsy findings raised the possibility of lympho-cytic vasculitis, the nickel allergy was confirmed, and the clip was replaced with a titanium one.

Like the one reported by Tan et al., our case reminds the neurosurgical community of the possibility of nickel sensitivity—acute or chronic. When possible, screening can be used. Given the 10%–15% rates of nickel allergy, which are higher in women, we also advocate for the rou-tine use of medical-grade titanium clips for aneurysm clip-ping. We agree with the authors that follow-up cerebral MRI can detect development of cerebral edema, but we wouldn’t advocate for its routine use in asymptomatic pa-tients given the rarity of this reaction after aneurysm clip-ping. We reported the findings of this case in our Mayfield Clinic blog.2 The blog addresses the public health issue of nickel allergy, reminding our patients and community to keep their medical histories up to date with a family mem-ber, and we note that even a small detail, such as allergic reaction to jewelry, could become vitally important.

ryan D. Tackla, MD1,2

Andrew J. ringer, MD1–3

1University of Cincinnati (UC) College of Medicine, Cincinnati, OH2Comprehensive Stroke Center at UC Neuroscience Institute,

Cincinnati, OH3Mayfield Clinic, Cincinnati, OH


references 1. Grande A, Grewal S, Tackla R, Ringer AJ: Life-threatening

allergic vasculitis after clipping an unruptured aneurysm: Case report, weighing the risk of nickel allergy. surg Neurol int 5 (suppl 4):S161–S164, 2014

2. Kemper M: allergic to nickel? Be sure to let your doctor know! (http://www.mayfieldclinicblog.com/allergic-to-nick-el-be-sure-to-let-your-doctor-know/) [Accessed April 8, 2015]

3. Tan T, Tee JW, Han TF: Cell-mediated allergy to cerebral aneurysm clip causing extensive cerebral edema. J Neuro-surg 121:924–928, 2014

responseWe read with interest the case report by Grande et al.1

and their attendant Letter to the Editor. Key histopathological and clinical differences exist be-

tween our original report and that of Grande et al.1 In our paper, a local Type IV hypersensitivity reaction represent-ed by intraparenchymal histiocytic infiltrates occurred in the area adjacent to where the Phynox aneurysm clip was placed. This presented as increased intracranial pressure and headaches. In contrast, the case reported by Grande et al. demonstrated mainly perivascular lymphocytic cuffing. This presented with what the authors have appropriately termed an allergic vasculitis of the CNS, with seizures and ischemic infarctions secondary to multifocal stenosis of the major intracranial arteries surrounding the nickel-containing clip. The multidisciplinary diagnosis of aller-gic vasculitis is supported by the temporal relationship between clipping and clinical re-presentation and deterio-ration, histopathological findings, and clinical stabiliza-tion after clip replacement with an Aesculap titanium clip.

The report by Grande et al.1 supports the fact that im-munological reactions to nickel-containing aneurysm clips can result in a spectrum of clinical presentations, from low-grade, relapsing-remitting symptoms to life-threatening conditions. A documented allergy to nickel is helpful for diagnosis, but given the relatively high prevalence of nick-el contact dermatitis and the rarity of allergic reactions to nickel-containing clips, a high degree of clinical suspicion remains of paramount importance. As mentioned previ-ously, the increasing use of titanium-based clips can nul-lify the risk of nickel allergy in aneurysm clipping.

Terence Tan, MBBSJin W. Tee, MBBS, MD

Tiew F. Han, MBBS, FrAcSSt. Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia

reference 1. Grande A, Grewal S, Tackla R, Ringer AJ: Life-threatening

allergic vasculitis after clipping an unruptured aneurysm: Case report, weighing the risk of nickel allergy. surg Neurol int 5 (suppl 4):S161–S164, 2014


Vertebral artery pexy for microvascular decompression

TO THE EDITOR: I read the article by Ferreira et al.2 with great interest (Ferreira M Jr, Walcott BP, Nahed BV, et al: Vertebral artery pexy for microvascular decom-pression of the facial nerve in the treatment of hemifacial spasm. J Neurosurg 114:1800–1804, June 2011). The of-fending vessels in hemifacial spasm vary. Compression by an anterior inferior cerebellar artery (AICA) or posterior inferior cerebellar artery (PICA) is common, but compres-





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sion by a vertebral artery (VA) is not rare, although in most cases there is a PICA between the VA and the facial nerve. In my personal experience of 500 cases of hemifa-cial spasm, the frequency of VA-related compression has been around 20%.5 Thus, how to decompress this big ves-sel is an important issue in microvascular decompression for hemifacial spasm.

Ferreira et al. described being able to treat VA compres-sion by transposing the VA and suturing it to the clival or petrous dura safely. The procedure seemed to be effective in all 6 cases, but I feel uneasiness regarding the safety. The authors reported 1 case of “transient” vocal cord pa-ralysis. In general, the neurological recovery from palsy of lower cranial nerves (especially CN IX and X) is not easy. In most patients, swallowing and hoarseness improves to an almost normal functional level, but their vocal cord movement remains still paralytic. Compensation with the other vocal cord makes the symptoms better.4 Without a laryngeal fiberscope, it cannot be concluded that the lower cranial nerve damage was fully resolved. Thus I want to know if the authors examined the patient’s vocal cord with a fiberscope or asked any otolaryngologist to evaluate it.

In addition to the vocal cord paralysis, the authors re-ported a case of hearing loss (16.7%). The reported inci-dences of hearing loss are around 2%–3%1 and 1 case in 6 patients is an exceedingly high rate. In the literature, hemi-facial spasm with VA compression is described as being surgically treated with less morbidity.3

In summary, I have concerns about the safety of this procedure and want to hear from the authors regarding this point as well as the status of the lower cranial nerves of the patient with “transient” palsy.

Takamitsu Fujimaki, MD, PhDSaitama Medical University, Moroyama, Japan


references 1. Barker FG II, Jannetta PJ, Bissonette DJ, Shields PT, Larkins

MV, Jho HD: Microvascular decompression for hemifacial spasm. J Neurosurg 82:201–210, 1995

2. Ferreira M Jr, Walcott BP, Nahed BV, Sekhar LN: Vertebral artery pexy for microvascular decompression of the facial nerve in the treatment of hemifacial spasm. J Neurosurg 114:1800–1804, 2011

3. Kim JP, Park BJ, Choi SK, Rhee BA, Lim YJ: Microvas-cular decompression for hemifacial spasm associated with vertebrobasilar artery. J Korean Neurosurg soc 44:131–135, 2008

4. Sulica L: The natural history of idiopathic unilateral vo-cal fold paralysis: evidence and problems. laryngoscope 118:1303–1307, 2008

5. Fujimaki T, Son JH, Tsuchiya Y, Hirata M, Murakami H, Ishii T, et al: [Hemifacial spasm caused by vertebral artery compression: etiological consideration based on demographic data and review of the surgical procedure.] Jpn J Neurosurg (Tokyo) 14:78–83, 2005 (Jpn)

responseWe thank Dr. Fujimaki for his very insightful comments

regarding our manuscript. Most large series include all of-

fending vessels (AICA, PICA, and VA) causing hemifacial spasm. The rate of VA compression has been found to be 24% in a series of 782 patients,1 which is in line with Dr. Fujimaki’s personal experience. It cannot be understated that our series of 6 cases treated with VA pexy were most severe, with impressive compression. The majority of our own patients undergo microvascular decompression of the AICA, PICA, or veins compressing the facial nerve with the use of Teflon felt pieces, with an excellent outcome. The senior author has not observed any cases of hearing loss in such patients in the last 10 years. The senior author has also observed the failure of microvascular decompres-sion of the enlarged VAs when only Teflon felt or other padding was used. Looking at the physics of vascular com-pression of a cranial nerve, when the compressive artery is large, atherosclerotic, or calcified, it is not likely that any amount of padding will “decompress” the nerve, or even dampen the pulsations. Therefore, one needs to mobilize the artery completely away from the nerve, or vice versa.

Neurophysiological monitoring using lateral spread as an indication of resolution of spasm is applied in all of our cases. In addition, we employ the monitoring of hearing function, and of lower cranial nerve function, in patients with large-vessel compression. That being said, we agree with Dr. Fujimaki’s comments that both lower cranial nerve dysfunction and hearing loss are distressing com-plications. We attribute the lower cranial nerve dysfunc-tion and hearing loss to increased manipulation of the offending vessel. In the patient described with vocal cord paralysis, the condition had improved at 1 year following the procedure (as observed by direct laryngoscopy), and subsequently had resolved completely at 2 years after sur-gery. Hearing loss was seen in 1 of 6 cases. In this case the patient had trigeminal neuralgia and hemifacial spasm due to severe vascular compression by the vertebral artery. The rate of hearing loss after microvascular decompression procedures has been found to be 2.7% in larger series.1 It is unknown whether those cases of hearing loss were due to severe compression due to VA ectasia or involved compres-sion from smaller vessels. The small size of our case series will inflate any complication rates. The pexy of the VA that we have described is a technically more involved procedure and must be weighed against the potential hazards in the treatment algorithm.

Since our article was published, an additional 5 cases of hemifacial spasm caused by VA compression have been treated with a pexy procedure (most of these patients had other arteries or veins compressing the facial nerve in ad-dition to the VA) have been treated with a pexy procedure. One of these 5 patients had a transient lower cranial nerve weakness, which resolved within 2 months. None of these 5 patients had hearing loss as a complication. All of the patients were cured of hemifacial spasm.

It should also be noted that, increasingly, most patients with hemifacial spasm are being referred to us after re-ceiving Botulinum toxin injections for treatment of the condition over the course of many years. The longer dura-tion of the hemifacial spasm may accentuate the compres-sion of the facial nerve by the VA due to the progression of atherosclerotic change. It may also make the cure of the hemifacial spasm by simple microvascular decompression more difficult.



Neurosurgical forum

Laligam N. Sekhar, MDManuel Ferreira Jr., MD, PhD

University of Washington, Seattle, WA


reference 1. Barker FG II, Jannetta PJ, Bissonette DJ, Shields PT, Larkins

MV, Jho HD: Microvascular decompression for hemifacial spasm. J Neurosurg 82:201–210, 1995


Neoadjuvant chemotherapy to maximize glioblastoma resection in the elderly

TO THE EDITOR: We read with great interest the ar-ticle from Oszvald et al.3 (Oszvald Á, Güresir E, Setzer M, et al: Glioblastoma therapy in the elderly and the impor-tance of the extent of resection regardless of age. J Neuro-surg 116:357–364, February 2012). For almost a century, treatment of most high-grade gliomas has started with maximum safe resection. In this setting, this study may not seem to be a novel observation. However, while the impact of the extent of resection on the survival of patients

with glioblastoma (GBM) is still questionable, the authors’ take-home message could very well change our approach to malignant gliomas, especially in elderly patients. The number of elderly patients with GBM can be expected to continue to increase as the proportion of elderly patients continues to grow, and the challenges of treating these pa-tients are increased by the lack of randomized controlled studies involving this population. The lesson we learned from supratentorial low-grade gliomas in older patients2 is similar to the conclusion of Oszvald et al., strongly sug-gesting that treatment decisions in the elderly should fol-low the same criteria as in younger patients, with complete or extensive surgery as the goal.3 However, despite the in-novative microsurgical armamentarium that is currently available, complete resection of GBM is often impossible due to the highly infiltrative nature of these tumors, their multiplicity, and their location within deep-seated or elo-quent areas.

How can we enhance the chances for a complete surgery?Here we present the case of a 66-year-old patient har-

boring a GBM within the whole left frontal lobe (Fig. 1A). Extensive involvement of this eloquent area prevented us from performing a complete resection and nonsurgical treatments were thought to represent a valuable therapeutic alternative. Thus, we considered a combination of temo-zolomide (TMZ) and bevacizumab (BV) as initial treat-ment. Eight weeks later (after 2 monthly cycles of TMZ and 2 biweekly cycles of BV), MRI showed partial regres-sion of peritumoral edema and mass effect and moderate reduction in the size of the tumor (Fig. 1B). No toxicity or side effects were evident. This tumor shrinkage allowed us to perform a gross-total resection. No excessive hemor-

Fig. 1. A: Pretreatment axial contrast-enhanced CT scan showing a large and heterogeneous left frontoinsular tumor exerting significant mass effect. B: Preoperative axial Gd-enhanced T1-weighted MR image showing markedly reduced mass effect and volume. c: Postoperative axial fluid-attenuated inversion recovery (FLAIR) MR image showing gross-total removal of the tumor.




Neurosurgical forum

rhage was noted. The patient’s postoperative course was uneventful, and no language disorder was noted. Brain MRI confirmed the gross-total resection (Fig. 1C). Sub-sequently, the patient completed concomitant radiotherapy and chemotherapy (an additional 6 cycles of TMZ-based treatment).

Although the feasibility of neoadjuvant chemotherapy with the aim of optimizing surgery is classically reported and frequently used in the treatment of non-neurological malignancies, there are only two previous works reporting its use in the neurological oncology literature.1,4

To the best of our knowledge, there is no case series assessing the feasibility of this strategy in patients with GBM. Using BV in addition to TMZ is not only feasible and safe, even in a neoadjuvant setting, but it also has the benefit of reducing the tumor, allowing for safe gross-total removal of a previously “unresectable” high-grade tumor. This strategy can also be used in “resectable” GBM in-volving non-eloquent areas. In these cases, where more than 90% of recurrences in GBM occur within 2 cm of the original tumor, we suggest that this neoadjuvant che-motherapy be followed by resection beyond the apparent tumor boundaries, the so-called “supratotal” resection, if possible.5 In this way, we might be able to prevent tumor recurrence.

However, further studies and longer follow-up are nec-essary in order to provide evidence of whether this thera-peutic strategy satisfies our expectations and improves the survival of patients with GBM. Since older patients are systematically excluded from multimodal treatment trials, we strongly suggest that this novel therapeutic approach utilizing neoadjuvant chemotherapy in an attempt to ex-tend tumor resection may be further studied in prospective trials confined to elderly patients with GBM.

gentian Kaloshi, MDArben rroji, MD

Mentor Petrela, MDUniversity Hospital Center “Mother Theresa,” Tirana, Albania


AcknowledgmentWe express our gratitude to Prof. Jean-Yves Delattre for his

valuable comments on this topic.

references 1. Duffau H, Taillandier L, Capelle L: Radical surgery after

chemotherapy: a new therapeutic strategy to envision in grade II glioma. J Neurooncol 80:171–176, 2006

2. Kaloshi G, Psimaras D, Mokhtari K, Dehais C, Houillier C, Marie Y, et al: Supratentorial low-grade glioma in older patients. Neurology 73:2093–2098, 2009

3. Oszvald Á, Güresir E, Setzer M, Vatter H, Senft C, Seifert V, et al: Glioblastoma therapy in the elderly and the importance of the extent of resection regardless of age. J Neurosurg 116:357–364, 2012

4. Voloschin AD, Louis DN, Cosgrove GR, Batchelor TT: Neo-adjuvant temozolomide followed by complete resection of a 1p- and 19q-deleted anaplastic oligoastrocytoma: case study. Neuro oncol 7:97–101, 2005

5. Yordanova YN, Moritz-Gasser S, Duffau H: Awake surgery for WHO Grade II gliomas within “noneloquent” areas in the

left dominant hemisphere: toward a “supra-total” resection. Clinical article. J Neurosurg 115:232–239, 2011


nal article.


endovascular treatment of wide-necked aneurysms

TO THE EDITOR: I congratulate Durst et al.2 on their experience and results with the dual (or double) microcath-eter technique for the coiling of wide-necked intracranial aneurysms (Durst CR, Starke RM, Gaughen JR Jr, et al: Single-center experience with a dual microcatheter tech-nique for the endovascular treatment of wide-necked an-eurysms. J Neurosurg 121:1093–1101, November 2014). I personally appreciated their acknowledgment of my first conception of the method.1 I wish to clarify that in our original report, the technique was not used for “rescue” as the authors have suggested. Rather, we observed coil insta-bility in the sac, and/or coil herniation through the neck, during deployment from a single microcatheter. I believe these remain the main indications for the technique today. Its use for endovascular rescue3 following coil perforation arose a few years later, and is of course another good in-dication.

Stephen P. Lownie, MD, FrcScLondon Health Sciences Centre, London, ON, Canada


references 1. Baxter BW, Rosso D, Lownie SP: Double microcatheter

technique for detachable coil treatment of large, wide-necked intracranial aneurysms. aJNr am J Neuroradiol 19:1176–1178, 1998

2. Durst CR, Starke RM, Gaughen JR Jr, Geraghty S, Kreitel KD, Medel R, et al: Single-center experience with a dual microcatheter technique for the endovascular treatment of wide-necked aneurysms. J Neurosurg 121:1093–1101, 2014

3. Willinsky R, terBrugge K: Use of a second microcatheter in the management of a perforation during endovascular treatment of a cerebral aneurysm. aJNr am J Neuroradiol 21:1537–1539, 2000


nal article.





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