Neurosurgical forum Letters to the editor

Aneurysm rupture Response: In their article, Suzuki and colleagues stated that active bleeding was observed with increasing To The Editor: We read with interest the article by enhancement in 25.5% of patients (13 of 51).1 All patients Tsuang and colleagues2 (Tsuang FY, Su IC, Chen JY, et al: with extravasation had Claassen Grade 3 or 4 and World Hyperacute cerebral aneurysm rerupture during CT an- Federation of Neurosurgical Societies (WFNS) Grade III, giography. Clinical article. J Neurosurg 116:1244–1250, IV, or V. The other group without extravasation included June 2012), in which they described 21 subarachnoid patients in all grades. In our series of patients with acute hemorrhage (SAH) patients with active contrast extrava- extravasation on CTA, those who presented with a good sation from a ruptured aneurysm during initial cerebral neurological status initially, mainly those with WFNS CT angiography (CTA). They divided these patients with Grade I or II, had the chance for a favorable outcome “reruptured” aneurysms into two subgroups: those with a if timely and successful decompressive surgery and ap- good initial neurological status who showed rapid neuro- propriate aneurysm obliteration were done. Those who logical deterioration, and those with a poor neurological showed a poor neurological status at presentation died no status. The former may still have a favorable outcome if matter what kind of treatment they received. they undergo timely and successful decompressive sur- In our article, the group with favorable outcomes gery and appropriate aneurysm obliteration; there is no that had presented with a good neurological status ex- effective treatment for the latter. perienced rebleeding from the aneurysm during CTA, We recently surveyed a series of patients with SAH and thus further neurological deterioration was reason- who underwent CT perfusion (CTP) with 18-phase dynam- able. Patients who had an initial poor neurological sta- ic enhancement, confirmed the presence of extravasated tus showed extravasation during CTA, indicating that contrast medium in the source image, and reported that ac- primary active bleeding of the aneurysms had not been tive bleeding from an aneurysm was observed with increas- stopped yet or that those aneurysms bled again, but this ing enhancement in 25.5% (13 of 51 cases).1 All CTP results could not be clarified. Their neurological status remained in patients with extravasation were obtained within 2 hours poor throughout the clinical course. of its onset. Moreover, the incidence of active bleeding in The time from ictus to the CT suite also matters. If that patients scanned within 2 hours was 42.3% (11 of 26 cases). period is relatively long and if neurological status deterio- We believe that bleeding from a ruptured aneurysm rates abruptly during the examination, rebleeding is more is arrested immediately when the intracranial pressure is likely. There must be another small group of patients whose increased to the level of the systolic blood pressure.1 We primary bleeding was not stopped and whose bleeding was could observe rerupture from an aneurysm by the extrav- so minimal that we could detect the primary bleeding on asation of contrast material from the aneurysm on intra- CTA with intra-examination neurological deterioration. arterial angiography in patients with marked changes in If the extent of extravasation is great and the time vital and neurological signs. We have encountered many from ictus to CTA examination is long, then rebleeding is patients with extravasation of contrast material during more likely; if the time from ictus to examination is short, CTA and CTP without marked neurological deterioration, then extravasation might indicate either primary bleeding which may reflect the inclusion of patients with continuous or rebleeding. At that time, the best indicator for differ- bleeding, as seen with other systematic injuries. It is time entiation is whether the clinical neurological status dete- to recognize that extravasation from an aneurysm on CTA riorates. Our article emphasized that timely intervention and CTP does not always mean rerupture and that bleeding might offer better outcomes for any patients with acute from an aneurysm is not arrested immediately. extravasation, except those who present with a poor neu- Yasuhiro Kuroi, M.D. rological status initially. Kazufumi Suzuki, M.D. Fon-Yih Tsuang, M.D. Hidetoshi Kasuya, M.D. Chung-Wei Lee, M.D. Tokyo Women’s Medical University Medical Center East Kuo-Chuan Wang, M.D. Tokyo Women’s Medical University National Taiwan University Hospital Tokyo, Japan Taipei City, Taiwan Disclosure Reference The authors report no conflict of interest. 1. Suzuki K, Tanaka N, Morita S, Machida H, Ueno E, Kasuya H: References Active bleeding in acute subarachnoid hemorrhage observed by multiphase dynamic-enhanced CT. AJNR Am J Neurora­ 1. Suzuki K, Tanaka N, Morita S, Machida H, Ueno E, Kasuya H: diol 33:1374–1379, 2012 Active bleeding in acute subarachnoid hemorrhage observed by multiphase dynamic-enhanced CT. AJNR Am J Neurora­ diol 33:1374–1379, 2012 2. Tsuang FY, Su IC, Chen JY, Lee JE, Lai DM, Tu YK, et al: Hy- Please include this information when citing this paper: published peracute cerebral aneurysm rerupture during CT angiography. online December 6, 2013; DOI: 10.3171/2012.11.JNS121816. Clinical article. J Neurosurg 116:1244–1250, 2012 ©AANS, 2014

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Intracranial pressure monitoring and monitor ICP or not. In order to address known parameters traumatic injury that independently affect 2-week mortality, we adjusted for score, hypotension, age, pupil examination findings, and CT parameters. After this ad- To The Editor: We are interested in the clinical re- search of Farahvar et al.1 (Farahvar A, Gerber LM, Chiu justment, patients treated without ICP monitoring had a YL, et al: Increased mortality in patients with severe trau- significantly higher mortality than those treated with ICP matic brain injury treated without intracranial pressure monitoring. Patients who had a do not resuscitate order or monitoring. Clinical article. J Neurosurg 117:729–734, lacked brainstem reflexes were not included in the analy- Oc­to­ber 2012). sis. Severe traumatic brain injury (TBI) often leads to a Jamshid Ghajar, M.D., Ph.D. Brain Trauma Foundation high mortality rate. Therefore, intensive monitoring of New York, NY intracranial pressure (ICP) or imaging studies is crucial to save the patient’s life. Farahvar et al.1 used a massive, prospectively enrolled database to identify the effect of Please include this information when citing this paper: published ICP monitoring on the 2-week mortality of patients with online December 20, 2013; DOI: 10.3171/2012.11.JNS121675. severe TBI. They found that several parameters, including ©AANS, 2014 age, initial Glasgow Coma Scale score, low blood pres- sure, and CT findings, were correlated with the 2-week The lucid interval and the role of Benjamin mortality. Moreover, patients of all ages who underwent ICP monitoring had decreased mortality at 2 weeks (p = Bell 0.02) compared with those who did not have ICP monitor- 2 To The Editor: Ganz is to be congratulated on his ing. detailed description of our evolving understanding of the Since this is not a randomized controlled trial, it lucid interval following skull trauma in which he kindly would be unavoidable not to have some potential inter- acknowledges my careful reading over of the text (Ganz fering factors, such as family decision on whether or not JC: The lucid interval associated with epidural bleeding: to resuscitate the patient, comorbidities, associated major 2 evolving understanding. Historical vignette. J Neurosurg trauma, and the extent of primary underlying brain injury, 118:739–745, April 2013). However, this was not as care- that contribute to mortality. ful as it should have been, as I must take issue with the Despite these minor limitations, the authors’ study statement that in Benjamin Bell’s A System of Surgery has called on neurosurgeons to pay more attention to per- “there is absolutely no mention of a symptom-free lucid forming ICP monitoring to improve the outcome in pa- interval between injury and deterioration.” Nor is it true tients with severe TBI. Further large-scale randomized to say that “There is nothing in his A System of Surgery to controlled trials for consideration of ICP monitoring in show he understood the time element separating concus- patients with severe TBI are warranted to reduce the mor- sion and compression.” tality rate. Bell describes the lucid interval on more than one oc- Yu-Li Peng casion in chapter 4 of his A System of Surgery,1 expressing Nien-Tzu Liu the concept on page 171 in section 5, when he writes “In Ding-Yuan Peng every case, indeed, of injuries done to the head, in which Yu-Tse Hsieh the symptoms do not commence till several days after the Dueng-Yuan Hueng, M.D., Ph.D. Tri-Service General Hospital accident, as it is clear that the cause of the disorder has not National Defense Medical Center originally affected the brain or its membranes, for if it did Taipei, Taiwan so its effects would be immediate, it is probable that it op- erates almost solely by forming some effusion externally between the pericranium and the skull.” Disclosure Bell appreciated the dangers of posttraumatic cere- The authors report no conflict of interest. bral compression, for when describing on page 117 “cases of extravasation,” he goes on to say, “A patient, in such circumstances, we suppose to be in great hazard, from the References brain being compressed in one part or another: unless this 1. Farahvar A, Gerber LM, Chiu YL, Carney N, Härtl R, Ghajar compression be removed by an operation, he must in all J: Increased mortality in patients with severe traumatic brain probability die.” injury treated without intracranial pressure monitoring. Clini- Bell describes on page 115 circumstances when the cal article. J Neurosurg 117:729–734, 2012 trepan is indicated “without any appearance either of 2. Wilberger JE Jr, Harris M, Diamond DL: Acute subdural he- fracture or depression” and states that “The sole object matoma: morbidity, mortality, and operative timing. J Neuro­ of the operation of the trepan is to remove compression surg 74:212–218, 1991 from the brain.” As other surgeons like Pott would only trepan in the presence of a fracture, I would argue that Response: We thank Peng and colleagues for the let- Bell did indeed appreciate the mechanics and time scales ter on our paper. Our study was a prospective severe TBI of posttraumatic compression and the need for its relief by study, but patients were not randomized. The neurosur- operation. geons in the respective trauma centers made a decision to Bell’s A System of Surgery was popular and influen-

J Neurosurg / Volume 120 / March 2014 779 Unauthenticated | Downloaded 09/24/21 09:17 AM UTC Neurosurgical forum tial in Europe and America, and he deserves more credit sentation of epidural bleeding. What is described in this for his contribution. section of the book is a pattern of delayed infection, no lon- Iain Macintyre, M.D., F.R.C.S.Ed., F.R.C.P.E. ger seen today but first described by Pott.6 An important Edinburgh, United Kingdom detail is that the delay is always several days. The delays before deterioration following epidural bleeding with few 2 Disclosure exceptions last for some hours to a day or two, very rarely several days. The lucid interval due to extravasation as we The author reports no conflict of interest. understand it was first properly described by Abernethy, as mentioned in my paper, and was made more detailed 2 3 References by Hutchinson and subsequently Jacobson. As outlined in the paper, all the earlier so-called lucid intervals refer to 1. Bell B: A System of Surgery, ed 7. Edinburgh: Bell and Bad- the above-mentioned pattern of delayed infection. fute, 1801 Thus, while naturally appreciating Professor Mac­ 2. Ganz JC: The lucid interval associated with epidural bleeding: evolving understanding. Historical vignette. J Neurosurg 118: intyre’s interest in this paper I have no alternative but to 739–745, 2013 respectfully disagree with his arguments and conclusions. Benjamin Bell’s A System of Surgery was in its own day criticized as plagiarism by John Bell4 (1763–1820), also in Response: I was very happy when Professor Ma- cintyre agreed to discuss, analyze, and read this paper. He Edinburgh, a surgeon and the brother of the famous Sir Charles Bell (1774–1842). (The two Bell families were not is a distinguished retired general surgeon (Vice President 5 of the Royal College of Surgeons of Edinburgh and also related.) It was criticized by Sylvestor O’Halloran (1728– Queen’s surgeon). He is also still the history editor of the 1807), who wrote, Journal of the Royal College of Physicians of Edinburgh. A much later author seems to have bestowed no small In this journal he published a most informative paper on pains and labour, to illustrate this very interesting subject [head Benjamin Bell (1749–1806), which was the reason we injuries]; nor does he forget to pay himself some compliments on his success; “but, however diffident I am” (says he) “in came into contact, since the paper mentions that one of first dissenting from an established doctrine, IF MY OWN Bell’s teachers was a Dumfries surgeon whom I was and EXPERIENCE IS FOUND TO JUSTIFY THIS DISSENT, the am investigating. The title of the paper is “Scientific sur- more respectable the authority, by which the contrary opinion geon of the Enlightenment or ‘plagiarist in everything’: a is supported, the more I think necessary to investigate the mer- reappraisal of Benjamin Bell (1749-1806).”4 its of it.” But, alas! on a close and critical examination of this Nonetheless, I fear I must disagree with Professor performance it will appear, that observations and experience, Macintyre’s comments. Let us take each of the issues in almost every where militate against his assertions and opin- turn. ions—for they are nothing more. First are the comments about page 117 in Bell’s A Sys- In conclusion, it would be incorrect for me to com- tem of Surgery.1 There is no discussion that Bell under- ment on any aspect of Benjamin Bell’s work except neu- stood the dangers of extravasated fluids pressing on the rosurgery, because such writings are outside my area of brain. In consequence he proposed the most aggressive competence. Within the field of , the only pol­icy of trepanation of any 18th-century author. How- new feature is his wish to perform far too many trepa- ever, this has nothing to do with a lucid interval, which is nations. The reasons for doing so are more informed by an issue of timing, not danger. The same argument applies enthusiasm than argument. The reason to find a given pro- to the statement on page 114. cedure indicated must rest on the demonstration that the The statement in my paper that reads “There is noth- risks of the procedure are less than the risks of avoiding ing in his A System of Surgery to show he understood the it. Bell does not present this argument lucidly, not least time element separating concussion and compression” because the only risk of surgery he describes is failure to would have been clearer if the words “due to epidural relieve pressure. More serious, this voluminous text was bleed­ing” had been added. Even so, the suggestion that he not supported by case studies, the use of which was, at his did have such an understanding is based on the following time, the norm. This absence also significantly reduces the statement from page 171 of the 1785 edition of his book: originality of his writing, so that as far as neurosurgery is In every case, indeed, of injuries done to the head, in which concerned, one is left with an impression of plagiarism as the symptoms do not commence till several days after the acci- claimed by John Bell,4 rather than originality. dent, as it is clear that the cause of the disorder has not original- Jeremy C. Ganz, M.A., Ph.D., F.R.C.S. ly affected the brain or its membranes, for if it did so its effects Ulverston, United Kingdom would be immediate, it is probable that it operates almost solely by forming some effusion externally between the pericranium and the skull References There are two difficulties with Professor Macintyre’s interpretation of this passage. Firstly, it is not usual for 1. Bell B: A System of Surgery, ed 3. Edinburgh: Elliot C, Vol III, 1785, p 171 epidural collections to accumulate on the outer surface of 2. Hutchinson J: Four lectures on compression of the brain. Clin the skull between the pericranium and the bone. Secondly Lect Reps London Hosp 4:10–55, 1867 this passage comes from a section on infection, where the 3. Jacobson WHA: On middle meningeal haemorrhage. Guys presenting delayed symptoms were headache and a tender Hosp Rep 43:147–308, 1886 swelling over the injury, which is not a characteristic pre- 4. Macintyre IMC: Scientific surgeon of the Enlightenment or

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‘plagiarist in everything’: a reappraisal of Benjamin Bell lar therapeutic targets in the future. Further multicenter (1749-1806). J R Coll Physicians Edinb 41:174–181, 2011 large-scale prospective studies of molecular target–based 5. O’Halloran S: A New Treatise on the Different Disorders adjuvant therapy for atypical meningiomas are warranted Arising from External Injuries of the Head. Dublin: Zacha- riah Jackson, 1793, pp 2–3 to reduce the recurrence. 6. Pott P: Observations on the Nature and Consequences of Dueng-Yuan Hueng, M.D., Ph.D. Those Injuries to Which the Head is Liable From External Yao-Feng Li, M.D. Violence. London: Hawes, Clarke, and Collins, 1768 Huey-Kang Sytwu, M.D., Ph.D. Tri-Service General Hospital National Defense Medical Center Taipei, Taiwan Please include this information when citing this paper: published online December 6, 2013; DOI: 10.3171/2013.9.JNS132035. Disclosure ©AANS, 2014 The authors report no conflict of interest. Atypical meningiomas References 1. Hu D, Wang X, Mao Y, Zhou L: Identification of CD105 (en­do­ To The Editor: We are highly interested in the clini- 5 glin)-positive stem-like cells in rhabdoid meningioma. J Neu­ cal article by Mair et al. (Mair R, Morris K, Scott I, et al: rooncol 106:505–517, 2012 Radiotherapy for atypical meningiomas. Clinical article. 2. Hueng DY, Sytwu HK, Huang SM, Chang C, Ma HI: Isolation J Neurosurg 115:811–819, October 2011). and characterization of tumor stem-like cells from human me- The role of radiotherapy for atypical meningioma is ningiomas. J Neurooncol 104:45–53, 2011 still debated and urgently needs further clarification. Mair 3. Kalamarides M, Stemmer-Rachamimov AO, Niwa-Kawakita et al.5 conducted the largest retrospective study to date to M, Chareyre F, Taranchon E, Han ZY, et al: Identification of a progenitor cell of origin capable of generating diverse menin- investigate the potential role of radiotherapy for atypical gioma histological subtypes. Oncogene 30:2333–2344, 2011 meningioma. Their study showed that postoperative radio- 4. Laurendeau I, Ferrer M, Garrido D, D’Haene N, Ciavarelli therapy revealed a significant advantage only in patients P, Basso A, et al: Gene expression profiling of the hedgehog who had undergone gross-total tumor resection. They con- signaling pathway in human meningiomas. Mol Med 16:262– cluded that radiotherapy is not adequate after first-time 270, 2010 removal of those lesions in which a gross-total resection 5. Mair R, Morris K, Scott I, Carroll TA: Radiotherapy for atypi- (Simpson Grade I or II) has been completed. They also cal meningiomas. Clinical article. J Neurosurg 115:811–819, suggested that any residual tumor shown on postoperative 2011 6. Rath P, Miller DC, Litofsky NS, Anthony DC, Feng Q, Frank- imaging should receive adjuvant radiosurgery instead of lin C, et al: Isolation and characterization of a population of conventional radiotherapy. Moreover, postoperative radio- stem-like progenitor cells from an atypical meningioma. Exp therapy after a first-time resection was recommended for Mol Pathol 90:179–188, 2011 residual tumor that is too large for radiosurgery and for which a subsequent surgery is not intended. Response: No response was received from the au- Radiotherapy has been applied in clinical tumor con- thors of the original article. trol for several decades. Once the tumors are radiosensi- tive, then they are presumed to be well controlled. Mair 5 et al. proposed that atypical meningioma did not respond Please include this information when citing this paper: published to conventional radiotherapy well when resection did not online December 13, 2013; DOI: 10.3171/2012.1.JNS111904. achieve Simpson Grade I or II, suggesting that a remnant ©AANS, 2014 of atypical meningioma would have some radioresistant parts. A recent update of molecular cell biology in tumor Anterior temporal lobectomy stem-like cells1–3,5 provided a better understanding of ra- dioresistance. Hueng et al.2 first isolated and character- ized the meningioma stem-like cells from WHO Grade To The Editor: We have read with great interest the I benign meningiomas and WHO Grade II atypical me- paper by Elliott et al.8 (Elliott RE, Bollo RJ, Berliner JL, ningioma. Meningioma stem-like cells exhibited radiore- et al: Anterior temporal lobectomy with amygdalohippo­ sistance, surviving after radiation delivery doses of 5, 10, campectomy for mesial temporal sclerosis: predictors of or 15 Gy in a sphere-form culture system. The theory of long-term seizure control. Clinical article. J Neurosurg meningioma stem-like cells1,2,6 or meningeal progenitor 119:261–272, August 2013). The authors’ study is an ef- cells3 was further proved by Rath et al.,6 Kalamarides et fort to identify the predictors of long-term seizure con- al.,3 and Hu et al.1 Currently, meningioma stem-like cells trol after anterior temporal lobectomy with amygdalohip- have been well characterized from either human menin- pocampectomy in patients affected by pharmacoresistant giomas1,2,6 or murine meningioma.3 temporal lobe associated with mesial temporal Molecular profiles of atypical meningiomas are one sclerosis (MTS). First of all, the authors should be con- of the potential breakthrough points in future study. Lau- gratulated on their excellent epilepsy outcomes (89% rendeau et al.4 characterized the molecular pathway in modified Engel Class I at 6.7 years of median follow-up) the Hedgehog signaling pathway from WHO Grade I, II, in a homogeneous study of pharmacoresistant temporal and III human meningiomas, providing novel molecu- lobe epilepsy associated with MTS. We agree with the

J Neurosurg / Volume 120 / March 2014 781 Unauthenticated | Downloaded 09/24/21 09:17 AM UTC Neurosurgical forum authors about the importance of identifying factors that the factors predictive of seizure outcome. We suggest that predict seizure outcome in epilepsy surgery. However, we the recognition of the different subgroups of pathologi- think that more attention should be paid to the histological cal conditions associated with different seizure outcomes pattern facing the following issues. should stimulate the investigation of the specific epi- Besides the clinical, neurophysiological, and imaging leptogenic mechanisms, relating outcome mainly to the factors, the underlying histological type and subtype of pathological substrate. This approach is also in agreement MTS affecting the and dentate gyrus have with the recent suggestions of the International League emerged as having an increasing role in seizure outcome Against Epilepsy (ILAE) Commission on Classifications in the last years.2–5,7,10–13 Seizure prognosis in patients and Terminology1 to put more emphasis on the underlying undergoing epilepsy surgery for MTS has been hypoth- pathological substrate in the assessment of postsurgical esized to depend on either the subtype of hippocampal seizure outcome and in future epilepsy classifications. sclerosis4,5,13 or the status of the dentate gyrus, namely the Marco Giulioni, M.D. absence or presence of granule cell pathology (GCP).3,12 Matteo Martinoni, M.D. Indeed, the histopathological classification system for Gianluca Marucci, M.D., Ph.D. MTS recognizes 2 main groups, MTS Type 1a and 1b Bellaria Hospital (grouped into MTS Type 1 in the latest hippocampal scle- Bologna, Italy rosis classification),5 and 2 atypical variants, MTS Type 2 and Type 3, with a worse seizure outcome. Furthermore, Disclosure in 2009 a classification system for GCP was elaborated,3 distinguishing 3 different histological patterns: 1) no The authors report no conflict of interest. GCP, normal granule cell layer; 2) GCP Type 1, substan- tial granule cell loss; and 3) GCP Type 2, architectural References abnormalities in the granule cell layer, mainly granule 3 1. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van cell dispersion. Emde Boas W, et al: Revised terminology and concepts for In our retrospective study10 about seizure outcomes 8 organization of seizures and : report of the ILAE in drug-resistant mesial , in which Commission on Classification and Terminology, 2005-2009. we analyzed an MTS group as a whole, seizure outcome Epilepsia 51:676–685, 2010 was optimal, with Engel Class I9 outcomes in 82% of cas- 2. Blümcke I, Coras R, Miyata H, Ozkara C: Defining clinico- es (although Engel Class IA outcomes occurred in only neuropathological subtypes of mesial temporal lobe epilepsy 50%), whereas Engel Class II outcomes occurred in the with hippocampal sclerosis. Brain Pathol 22:402–411, 2012 remaining 18%. The various outcome classes were scat- 3. Blümcke I, Kistner I, Clusmann H, Schramm J, Becker AJ, Elger CE, et al: Towards a clinico-pathological classification tered among the different MTS subtypes. Regarding the of granule cell dispersion in human mesial temporal lobe epi- 14 patients with the best outcome, Engel Class IA was at- lepsies. Acta Neuropathol 117:535–544, 2009 tained in 11 (61%) of 18 patients with MTS Type 1a (with 4. Blümcke I, Pauli E, Clusmann H, Schramm J, Becker A, Elger or without GCP), in 2 (40%) of 5 patients with MTS Type C, et al: A new clinico-pathological classification system for 1b, and in 1 (20%) of 5 patients with MTS Type 2. Our mesial temporal sclerosis. Acta Neuropathol 113:235–244, findings suggested good results after surgery in patients 2007 with MTS Types 1a and 1b (MTS Type 1 in the latest 5. Blümcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, hippocampal sclerosis classification), with up to 80% of Bernasconi A, et al: International consensus classification of patients having Engel Class I outcomes. hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods. Considering the presence of GCP, we observed that Epilepsia 54:1315–1329, 2013 2 (20%) of 10 patients without GCP were in Engel Class 6. Coras R, Siebzehnrubl FA, Pauli E, Huttner HB, Njunting M, IA, while 12 (66.7%) of 18 patients with GCP attained Kobow K, et al: Low proliferation and differentiation capaci- complete seizure freedom. These findings indicated bet- ties of adult hippocampal stem cells correlate with memory ter postsurgical results in patients with GCP than in those dysfunction in humans. Brain 133:3359–3372, 2010 without GCP. The demonstration that a decreased poten- 7. da Costa Neves RS, Jardim AP, Caboclo LO, Lancellotti C, tial to generate neurospheres from the subgranular zone Marinho TF, Hamad AP, et al: Granule cell dispersion is not a is related to MTS and to alterations of dentate gyrus gran- predictor of surgical outcome in temporal lobe epilepsy with mesial temporal sclerosis. Clin Neuropathol 32:24–30, 2013 ule cells, especially in MTS Type 1b and GCP Type 1, 8. Elliott RE, Bollo RJ, Berliner JL, Silverberg A, Carlson C, suggests the existence of a relationship between dentate 11,12 Geller EB, et al: Anterior temporal lobectomy with amygda- gyrus pathology and postsurgical seizure outcome and lohippocampectomy for mesial temporal sclerosis: predictors 6 neuropsychological outcome. Indeed, these histologi- of long-term seizure control. Clinical article. J Neurosurg cal findings may have relevant prognostic implications 119:261–272, 2013 in seizure and neuropsychological outcomes in patients 9. Engel J Jr, Van Ness P, Rasmussen TB, Ojemann LM: Out- affected by hippocampal sclerosis as compared with pa- come with respect to epileptic seizures, in Engel J Jr (ed): Sur­ tients with other epileptogenic lesions (such as focal cor- gical Treatment of the Epilepsies, ed 2. New York: Raven tical dysplasia [FCD], glioneuronal tumors, or vascular Press, 1993, pp 609–621 10. Giulioni M, Marucci G, Martinoni M, Volpi L, Riguzzi P, lesions). Marliani AF, et al: Seizure outcome in surgically treated In our opinion, with the adoption of the more recent 2–5 drug-resistant mesial temporal lobe epilepsy based on the re- neuropathological classification systems, some sub- cent histopathological classifications. Clinical article. J Neu­ groups of pathological abnormalities conditioning out- rosurg 119:37– 47, 2013 comes have emerged and have to be considered among 11. Marucci G, Giulioni M, Rubboli G, Paradisi M, Fernández M,

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Del Vecchio G, et al: Neurogenesis in temporal lobe epilepsy: online January 3, 2014; DOI: 10.3171/2013.8.JNS131785. relationship between histological findings and changes in den- ©AANS, 2014 tate gyrus proliferative properties. Clin Neurol Neurosurg 115:187–191, 2013 12. Marucci G, Rubboli G, Giulioni M: Role of dentate gyrus al- Deep brain stimulation for obesity terations in mesial temporal sclerosis. Clin Neuropathol 29: 32–35, 2010 To The Editor: With great interest we have studied 13. Thom M, Liagkouras I, Elliot KJ, Martinian L, Harkness W, the article by Whiting et al.10 (Whiting DM, Tomycz ND, McEvoy A, et al: Reliability of patterns of hippocampal scle- Bailes J, et al: Lateral hypothalamic area deep brain stim- rosis as predictors of postsurgical outcome. Epilepsia 51: ulation for refractory obesity: a pilot study with prelimi- 1801–1808, 2010 nary data on safety, body weight, and energy metabolism. Clinical article. J Neurosurg 119:56–63, July 2013). This Response: We thank the authors for their insightful article is critical, primarily because it is a well-designed comments. Their work and remarks certainly coincide pilot study that explores a new application for deep brain with the direction in which the field is heading. In truth, stimulation (DBS) coupled with results that may give evi- we did a preliminary analysis of pathological findings in dence of an ability to modulate metabolic rate.4,10 These our series, but sufficient detail was not available for sub- results further support the existence of a hidden metabolic classification in the clinical reports. We plan to conduct circuit buried in our brain. Herein, we raise some concerns a blinded review of the pathology findings using the cur- regarding certain aspects of the theoretical framework de- rent classification systems to correlate such findings with sign of such a study. Our concerns are mainly because, seizure control. even though the aim of this study was safety, we still do There are 2 major shortcomings of postoperative not see the robust results as seen in DBS for Parkinson’s pathological analyses, however. First, there is currently disease (the main aspiration of this kind of study). Fur- no way to know the pathology classification before sur- thermore, there is still no strong explanation for why we gery. Therefore, this information cannot be used to guide did not observe results as impressive as those originally therapy or prognosticate. To fully realize the benefits seen in animal models.7,9 of correlative studies between subclassification of MTS Our comments on this paper are an attempt to high- pathology and outcomes, viable presurgical biomarkers light and address some aspects that, as we believe, should are necessary. Such biomarkers would allow for a priori be considered when a larger study is conducted for the prognostication on outcomes, thus providing better pre- sake of efficacy. These concerns are summarized in the surgical counseling to patients and families. following points: The second limitation of postoperative pathological 1) The stimulation strategies and parameters. The analysis is that we do not know what is left behind after intimate relationship between circadian system and feed resection. As Daniel Kahneman notes in Thinking, Fast homeostasis makes the neurocircuit of feeding a compli- and Slow, “what you see is all there is.” What may be cated one, and it becomes even more so in humans when more critical to failures in epilepsy surgery is not what we add the effect of higher centers in eating habits.2 On is seen, but what is left unseen or left behind. Thus, the one hand, this makes finding the optimal target for DBS pathological correlate for a poor surgical outcome may a challenging mission. On the other hand, using stimula- relate to the pathology available for analysis, the unre- tion parameters that are basically driven from the stimula- sected margins, or even distant regions. tion parameters utilized in movement disorders (with the The purpose of our study was to analyze our own ignorance of the circadian component) is a questionable methods of patient selection for single- or multistage epi- strategy in achieving the wanted efficacy. lepsy surgery for MTS to determine if our criteria were 2) Patient selection. One criterion of patient selection sound. We believe such results may help surgeons deter- in this study is based on nonresponse to bariatric surgery. mine who is best suited for single-stage surgery. We con- We believe it is important to know more details about this gratulate the advancement made in pathological analysis selection criterion in terms of why this type of surgery to help us further understand this disease and welcome failed in the patients and the pattern of failure. Recently new advancements to make the treatment of MTS more published data show that the patient’s genetic profile may successful and safe. play an important role in the success of bariatric surgery.6,8 Robert Elliott, M.D. This factor (the genetic profile) should be considered and Mainline Healthcare Neurosurgery addressed when exploring DBS for obesity. It may play a Newtown Square, PA role in the results of DBS as it does in bariatric surgery. Chad Carlson, M.D. Medical College of Wisconsin In this group of patients the cause of obesity may not sim- Milwaukee, WI ply be high food intake, which makes the ultimate goal of Werner Doyle, M.D. treatment to remedy this cause irrelevant. In fact, it has Orrin Devinsky, M.D. been shown that several genetic defects could lead to re- New York University Langone Medical Center fractory obesity. 2 Pairing the complicated organization of New York, NY appetite control with genetic factors raises the possibility Saint Barnabas Medical Center that refractory obesity (in patients in whom bariatric sur- Livingston, NJ gery has failed) may be associated with different types of corrupted neurocircuits. The possibility of different types of corrupted neurocircuits may imply that we may have Please include this information when citing this paper: published to utilize different targets (on a case by case basis, which

J Neurosurg / Volume 120 / March 2014 783 Unauthenticated | Downloaded 09/24/21 09:17 AM UTC Neurosurgical forum raises a question about the reasonability of investigating a 4. Eskandar E: Editorial. Deep brain stimulation and obesity. J novel application for DBS in this group of patients) rather Neurosurg 119:54, 2013 than utilizing 1 target for all cases. 5. Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, et al: Genetic ablation of orexin neurons in mice 3) What really is the physiological function of the results in narcolepsy, hypophagia, and obesity. Neuron 30: lateral hypothalamus? Even though targeting the lateral 345–354, 2001 hypothalamus is based on animal studies that have shown 6. Harrell LE, Decastro JM, Balagura S: A critical evaluation high-frequency stimulation or lesioning leading to weight of body weight loss following lateral hypothalamic lesions. loss, this somehow counteracts with other reports about Physiol Behav 15:133–136, 1975 the physiological function of this part of the hypothala- 7. Hatoum IJ, Greenawalt DM, Cotsapas C, Daly MJ, Reitman mus. To clarify this point, the orexinergic neurons of the ML, Kaplan LM: Weight loss after gastric bypass is associated lateral have a main role in wakefulness and with a variant at 15q26.1. Am J Hum Genet 92:827–834, 2013 arousal.1 It is considered that they affect feeding through 8. Moleres A, Campion J, Milagro FI, Marcos A, Campoy C, 2,3,5 Garagorri JM, et al: Differential DNA methylation patterns modulating arousal levels. It was found that under food between high and low responders to a weight loss interven- restriction, the activity of orexinergic neurons increases tion in overweight or obese adolescents: the EVASYON study. in anticipation of food. That being said, we can speculate FASEB J 27:2504–2512, 2013 that modulating these neurons by high-frequency stimula- 9. Sani S, Jobe K, Smith A, Kordower JH, Bakay RA: Deep brain tion should lead to less anticipation of food, less arousal, stimulation for treatment of obesity in rats. J Neurosurg 107: and a lower metabolic rate, or more specifically, as seen in 809–813, 2007 orexinergic neuron–ablated mice, to narcolepsy in a study 10. Whiting DM, Tomycz ND, Bailes J, de Jonge L, Lecoultre V, Wilent B, et al: Lateral hypothalamic area deep brain stimula- conducted by Chemelli et al.3 or to narcolepsy, hypopha- 5 tion for refractory obesity: a pilot study with preliminary data gia, and late-onset obesity in a study done by Hara et al. on safety, body weight, and energy metabolism. Clinical ar- Interestingly, the last effect contradicts what is shown ticle. J Neurosurg 119:56–63, 2013 by inhibiting the lateral hypothalamus by DBS (high- 7,9 frequency stimulation) or by lesioning in rats. However, Response: We appreciate the thoughtful analysis Drs. orexinergic neuron–ablated mice seem more reliably to Salma and Al-Otaibi have provided on our article. Our mimic the effect of inhibiting the lateral hypothalamus comments to their concerns with the paper are summa- than does trying to inhibit this small area of the brain in rized below. First, we reiterate that the primary focus was the small animals surgically. This makes the article by one of safety given that this is the first reported series Hara et al. worth reading and thinking about to explain of humans implanted with chronic lateral hypothalamic why the effect of high-frequency stimulation does match DBS. The fact that the FDA regards DBS as a significant the effect of genetic ablation for neurons specifically lo- risk device puts significant constraints on clinical studies cated in the lateral hypothalamus. This is important to of new DBS targets and indications.3 Our efforts to sec- determine that we really understand the physiology of this ondarily look at efficacy are clearly limited by the sample area of the hypothalamus and that we really have a strong size and primary outcome design of the study. The small theoretical basis. sample size (n = 3) in this pilot study is a lamentable but Finally, we would like to congratulate Whiting and unavoidable reality of such government oversight into cer- colleagues on their pioneering work. Since the impact of tain medical device research. Nevertheless, we hope that such studies is profound, especially on other future ap- by demonstrating safety (with more than 2 years of follow- plications for DBS, it should be reviewed and discussed up) this study has surmounted the first hurdle in consider- from several angles and perspectives to guarantee optimal ing lateral hypothalamic DBS as a treatment for refractory progress. cases of obesity. Asem Salma, M.D. Our choice of standard movement disorder DBS pa- Illinois Neurological Institute University of Illinois College of Medicine, Peoria rameters as starting points for programming lateral hypo- Peoria, IL thalamic DBS in our patients was also based on the well- Faisal Al-Otaibi, M.D. established long-term safety of these parameters for DBS King Faisal Specialist Hospital and Research Centre in patients with movement disorders. We agree with Dr. Riyadh, Saudi Arabia Salma and Dr. Al-Otaibi that future studies of DBS for re- fractory obesity may benefit from a more complex patient Disclosure selection process in which patients in whom bariatric sur- gery has failed are preoperatively characterized by base- The authors report no conflict of interest. line resting metabolic studies and genetic studies. How- ever, despite the fact that dozens of obesity-related genes References have been identified, a genotype with high penetrance and high risk for obesity has not been uncovered.1 Moreover, 1. Abrahamson EE, Leak RK, Moore RY: The suprachiasmatic the growing pandemic of obesity in the developed world is nucleus projects to posterior hypothalamic arousal systems. not likely attributable to genetic changes or mutations but Neuroreport 12:435–440, 2001 2. Bechtold DA, Loudon AS: Hypothalamic clocks and rhythms more likely to environmental factors. in feeding behaviour. Trends Neurosci 36:74–82, 2013 Finally, we defend our choice of the lateral hypo- 3. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell thalamus as the best investigational target of DBS in T, Lee C, et al: Narcolepsy in orexin knockout mice: molecular obesity. Drs. Salma and Al-Otaibi correctly point out genetics of sleep regulation. Cell 98:437–451, 1999 that the physiology of the lateral hypothalamus remains

784 J Neurosurg / Volume 120 / March 2014 Unauthenticated | Downloaded 09/24/21 09:17 AM UTC Neurosurgical forum largely unknown and many of the neurons in the lateral ebellopontine angle, close to cerebrovascular structures, hypothalamus have been primarily shown to be involved cranial nerves, the brainstem, and the cerebellum. Tradi- with arousal. Interestingly, with certain DBS contacts and tional surgical treatment of these lesions carries high risks stimulation parameters we did observe rapid changes in for morbidity and some risks for mortality, even for well- arousal in our patients undergoing lateral hypothalamic trained neurosurgeons. The complications of cerebrospi- DBS. Similar to the dichotomy between the rational drug nal fluid leakage, vascular injury, neurological deficits, designers who want to fashion specific drugs based on and postoperative infection have been reported.2 Recent shapes of known receptors and the combinatorial chem- advances in stereotactic radiosurgery (SRS) have greatly ists who aim to find treatments regardless of mechanism reduced the risks of morbidity and mortality associated by rapidly screening through massive libraries of com- with the management of VSs. Lee et al.1 reported no radio- pounds, it remains to be seen if future new target DBS surgery-related instances of morbidity or mortality associ- surgery is encouraged more from new knowledge regard- ated with Gamma Knife stereotactic radiosurgery (GKS). ing the physiology of the brain or more from a continued However, an adverse radiation effect was found, with peri- curiosity about whether electrical stimulation can mimic focal edema, tumor enlargement, and cyst enlargement or augment the historical consequences of brain ablation. identified at a median of 26 months (range 3 months–6 Clearly, the lateral hypothalamus has been shown under years) after GKS. conditions of both lesioning and stimulation in animals Using PubMed, Sughrue et al.2 summarized the re- and humans to affect body weight, appetite, and metabo- sults of microsurgery from various institutions. In this lism. Similar to what movement disorder DBS and micro- study, the authors reviewed 100 articles providing in- electrode recording has done for basal ganglia physiology, formation on 32,870 patients; their analysis showed an DBS may prove to be a powerful tool for expanding our overall mortality rate of 0.2% (95% confidence interval knowledge of hypothalamic physiology and neural cir- [CI] 0.1%–0.3%). Twenty-two percent of patients (95% CI cuits.2 In fact, less invasive, ablative neurosurgery such as 21%–23%) suffered from at least 1 microsurgery-related single-session radiosurgery may someday be reconsidered complication other than those affecting cranial nerve VII for obesity once DBS has been used as a mapping tool for or VIII. Cerebrospinal fluid leakage was a complication brain function and physiology. We feel that the brain-obe- in 8.5% of patients (95% CI 6.9%–10.0%). This complica- sity link is strong enough to encourage continued study of tion rate was significantly increased when the translaby- DBS in this disease and hope our safety data provide the rinthine approach was used but was unaffected by the size green light for a larger efficacy-focused study. of the tumor. Vascular complications, such as ischemic Nestor D. Tomycz, M.D. injury or hemorrhage, were found in 1% of patients (95% Michael Y. Oh, M.D. CI 0.75%–1.2%). Neurological complications developed in Donald M. Whiting, M.D. 8.6% of cases (95% CI 7.9%–9.3%) and were less likely to Allegheny General Hospital Pittsburgh, PA occur with resection of smaller tumors (p < 0.0001) and use of the translabyrinthine approach (p < 0.0001). Infec- tions happened in 3.8% of cases (95% CI 3.4%–4.3%), and 78% of these were meningitis. These results were signifi- References cantly higher than those associated with SRS. 2 1. Bircan I: Genetics of obesity. J Clin Res Ped Endo (Suppl 1): The contribution made by Sughrue et al. in point- 54 –57, 2009 ing out instances of morbidity beyond audiofacial com- 2. Lozano AM, Snyder BJ, Hamani C, Hutchison WD, Dostrov­ plications after VS surgery alerts neurosurgeons to take sky JO: Basal ganglia physiology and deep brain stimulation. great precautions during decision making before choos- Mov Disorder 25 Suppl 1:S71–S75, 2010 ing a treatment modality. Contemporary advances in SRS 3. Tomycz ND, Cheng BC, Cantella D, Angle C, Oh MY, Whit- have resulted in a reduction of morbidity in the treatment ing DM: Pursuing new targets and indications for deep brain of VSs. Therefore, comparisons of complications related stimulation: considerations for device-related clinical research in the United States. Neuromodulation 14:389–392, 2011 to SRS and microsurgery should be carefully considered during the decision-making process. There is one minor concern that we have about this retrospective study. Patient demographic data should be Please include this information when citing this paper: published stratified based on patient age, sex, and underlying comor- online December 20, 2013; DOI: 10.3171/2013.9.JNS131887. bidities when performing a univariate and/or multivariate ©AANS, 2014 analysis of these morbidities, because advanced age car- ries higher risks of morbidity than younger age. Despite these limitations, the study by Sughrue et Morbidity in vestibular schwannoma surgery al.2 provides significantly potent evidence for neurosur- geons to use in advising patients on the published risks To The Editor: We are interested in the article by of complications other than injury to audiofacial nerves Sughrue et al.2 (Sughrue ME, Yang I, Aranda D, et al: Be- following microneurosurgery for VS. Further large scale, yond audiofacial morbidity after vestibular schwannoma prospective studies are mandatory to better address the surgery. Clinical article. J Neurosurg 114:367–374, Febru- potential risks of surgery for VS. ary 2011). Kuan-Nien Chou, M.D. Vestibular schwannomas (VSs) are located in the cer- Bing-Huang Tsai, M.D.

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Wen-Yen Huang, M.D. lead to a more in-depth view of tumor biology in this dis- Dueng-Yuan Hueng, M.D., Ph.D. ease. Furthermore, an analysis of the molecular profiles Tri-Service General Hospital in VSs would yield more information about the functional National Defense Medical Center Taipei, Taiwan roles of key proteins regulating tumor growth, such as os- teopontin2,4,7 and Nodal in brain tumors.1,3 In the modern genomics era, knowledge of more Disclosure messages in the tumor biology of VS could lead to novel The authors report no conflict of interest. breakthroughs in hearing preservation. Despite these mi- nor limitations, the studies by Sughrue and colleagues have provided many valuable references for clinicians in References the management of VS. Additional prospective studies in clinical practice are necessary to prevent patients from 1. Lee CC, Yen YS, Pan DH, Chung WY, Wu HM, Guo WY, et al: losing their hearing. Delayed microsurgery for vestibular schwannoma after gamma Dueng-Yuan Hueng, M.D., Ph.D. knife radiosurgery. J Neurooncol 98:203–212, 2010 Huey-Kang Sytwu, M.D., Ph.D. 2. Sughrue ME, Yang I, Aranda D, Rutkowski MJ, Fang S, Tri-Service General Hospital Cheung SW, et al: Beyond audiofacial morbidity after vestib- National Defense Medical Center ular schwan­no­ma surgery Clinical article. J Neurosurg 114: Taipei, Taiwan 367–374, 2011 Disclosure Response: No response was received from the authors of the original article. The authors report no conflict of interest.

References Please include this information when citing this paper: published online December 20, 2013; DOI: 10.3171/2011.2.JNS11301. 1. Hueng DY, Lin GJ, Huang SH, Liu LW, Ju DT, Chen YW, et ©AANS, 2014 al: Inhibition of Nodal suppresses angiogenesis and growth of human gliomas. J Neurooncol 104:21–31, 2011 2. Jan HJ, Lee CC, Shih YL, Hueng DY, Ma HI, Lai JH, et al: Vestibular schwannoma growth and hearing Osteopontin regulates human glioma cell invasiveness and tu- mor growth in mice. Neuro Oncol 12:58–70, 2009 loss 3. Lee CC, Jan HJ, Lai JH, Ma HI, Hueng DY, Lee YC, et al: Nodal promotes growth and invasion in human gliomas. On­ cogene 29:3110–3123, 2010 To The Editor: We are interested in a clinical article 5 4. Lin CK, Tsai WC, Lin YC, Hueng DY: Osteopontin predicts by Sughrue et al. on hearing preservation (Sughrue ME, the behaviour of atypical meningioma. Histopathology 60: Kane AJ, Kaur R, et al: A prospective study of hearing 320–325, 2012 preservation in untreated vestibular schwannomas. Clini- 5. Sughrue ME, Kane AJ, Kaur R, Barry JJ, Rutkowski MJ, Pitts cal article. J Neurosurg 114:381–385, February 2011). We LH, et al: A prospective study of hearing preservation in un- propose comments to improve the quality of studying the treated vestibular schwannomas. Clinical article. J Neuro­ hearing course in the natural history of vestibular schwan- surg 114:381–385, 2011 6. Sughrue ME, Yang I, Aranda D, Lobo K, Pitts LH, Cheung nomas (VSs). SW, et al: The natural history of untreated sporadic vestibular A patient’s hearing course is one of the most worri- schwannomas: a comprehensive review of hearing outcomes. some issues in the management of VSs.5,6,8 Sughrue et al.5 Clinical article. J Neurosurg 112:163–167, 2010 performed their study to evaluate radiological images, pa- 7. Tseng KY, Chung MH, Sytwu HK, Lee HM, Chen KY, Chang tient profiles, and audiograms in patients with VSs. They C, et al: Osteopontin expression is a valuable marker for pre- showed that faster rates of tumor growth (> 2.5 mm/year) diction of short-term recurrence in WHO grade I benign me- are positively correlated with hearing loss. Importantly, ningiomas. J Neurooncol 100:217–223, 2010 8. Yang I, Sughrue ME, Han SJ, Aranda D, Pitts LH, Cheung the pearl of this study is a follow-up period longer than SW, et al: A comprehensive analysis of hearing preservation 10 years. The authors found a simple conclusion that all after radiosurgery for vestibular schwannoma. Clinical ar- patients lost their hearing acuity after a decade, regard- ticle. J Neurosurg 112:851–859, 2010 less of the initial tumor size, the patient’s age at diagno- sis, and the presence of neurofibromatosis Type 2. This Response: No response was received from the au- conclusion provides neurosurgeons with the information thors of the original article. needed to advise patients to take necessary steps during follow-up to VS treatment. Some minor limitations exist in the study of hearing Please include this information when citing this paper: published loss. First, what factors contribute to a faster rate of tumor online January 3, 2014; DOI: 10.3171/2011.9.JNS11459. growth? Personalized medicine is a rising issue of con- ©AANS, 2014 cern. More aggressive analyses of noninvasive magnetic resonance spectrography studies or minimally invasive means of obtaining cerebrospinal fluid prior to surgical Medial temporal epilepsy intervention would provide some potential clues in future studies. Moreover, genome-wide analyses of VSs would To The Editor: We have read with great interest the

786 J Neurosurg / Volume 120 / March 2014 Unauthenticated | Downloaded 09/24/21 09:17 AM UTC Neurosurgical forum paper by Hu et al.11 (Hu WH, Zhang C, Zhang K et al: Se- 2 (architectural abnormalities in the granule cell layer, lective amygdalohippocampectomy versus anterior tem- mainly granule cell dispersion).3 Our findings suggested poral lobectomy in the management of mesial temporal good results after surgery in patients with HS Type 1, with lobe epilepsy: a meta-analysis of comparative studies. A up to 80% of patients having Engel Class I outcomes. systematic review. J Neurosurg 119:1089–1097, Novem- Considering the presence of GCP, we observed that ber 2013). 2 (20%) of 10 patients without GCP were in Engel Class The authors’ study is an effort to compare seizure IA, while 12 (66.7%) of 18 patients with GCP achieved and memory outcomes after 2 surgical techniques gener- complete seizure freedom. These findings indicate better ally used for the surgical treatment of pharmacoresistant postsurgical results in patients with GCP compared with mesial temporal lobe epilepsy (MTLE)—that is, selective those without GCP. The decreased potential to generate amygdalohippocampectomy and anterior temporal lobec- neurospheres from the subgranular zone appears related tomy. First and foremost, the authors should be congratu- to MTS and to alterations of dentate gyrus granule cells, lated for their effort to perform an exhaustive meta-analy- especially in MTS Type 1b and GCP Type 1, suggest- sis of the pertinent literature concerning this still-debated ing the existence of a relationship between dentate gyrus issue. We obviously agree with the authors about the im- pathology and postsurgical seizure outcome10,14 and neu- portance of identifying the surgical approach for achiev- ropsychological outcome.7 ing the best seizure and neuropsychological outcomes. Indeed, these histological findings may have relevant However, we consider it useful to highlight a limitation of prognostic implications in seizure and neuropsychologi- this study represented by the lack of the histological data. cal outcomes for patients with HS compared to patients Indeed, an increasing role for underlying pathologi- with other epileptogenic temporal lobe lesions (such as cal disorders has emerged in recent years;2–8,10,12–16 there- FCD, glioneuronal tumors, or vascular lesions). In our fore, to better understand seizure and neuropsychological opinion, with the adoption of the more recent pathological outcomes in temporal lobe epilepsy surgery, more atten- classification systems,2–6,15 some subgroups of histologi- tion should be paid to the histological diagnosis. Seizure cal abnormalities influencing outcomes have emerged and prognosis of patients undergoing temporal lobe epilepsy should be considered among factors predictive of seizure surgery appears strictly related to the type of lesion.2– 4,7,8, outcome such as the type of surgical approach and the 10,12–16 Even neuropsychological dysfunction may be re- extent of resection. lated to the histological pattern of dentate gyrus granular This approach is also in agreement with the recent cell pathology (GCP) and preserved neurogenetic abil- suggestions of the International League Against Epilep­ 7,13 sy (ILAE) Commission on Classifications and Terminol- ity. In our retrospective study about seizure outcome 1 in drug-resistant MTLE10 treated with a tailored anterior ogy —that is, to put more emphasis on the underlying temporal lobectomy along with amygdalohippocampecto- pathological substrate in the assessment of postsurgical my, patients with MTLE and an epilepsy-associated low- seizure outcome and in future epilepsy classifications. Marco Giulioni, M.D. grade tumor, mesial temporal sclerosis (MTS), or MTS associated with focal cortical dysplasia (FCD) showed Matteo Martinoni, M.D. 9 Gianluca Marucci, M.D., Ph.D. the best postsurgical seizure outcome (Engel Class I in > IRCCS Bellaria Hospital 80% of cases), whereas only 63% of patients with isolated Bologna, Italy FCD achieved the same type of outcome. Our results support the thesis that the pathological Disclosure substrate represents a significant predictor of seizure re- currence, with rates of Engel Class I outcomes ranging The authors report no conflict of interest. from 59% for patients with isolated FCD to 82%, 83%, and 84%, respectively, for those with isolated MTS, ep- References ilepsy-associated low-grade tumor, and FCD associated with MTS. According to the recent literature,2–6,12–16 our 1. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van findings suggest that different pathological subtypes are Emde Boas W, et al: Revised terminology and concepts for associated with different postsurgery seizure outcomes. organization of seizures and epilepsies: report of the ILAE The analysis of seizure outcome in histopathological sub- Commission on Classification and Terminology, 2005-2009. Epilepsia 51:676–685, 2010 types of FCD showed different prognoses in the different 2. Blümcke I, Coras R, Miyata H, Ozkara C: Defining clinico- pathological subgroups, with worse outcomes for patients 10 neuropathological subtypes of mesial temporal lobe epilepsy with isolated FCD Type I. with hippocampal sclerosis. Brain Pathol 22:402–411, 2012 Analyzing the pathological group of MTS, we have 3. Blümcke I, Kistner I, Clusmann H, Schramm J, Becker AJ, El- to consider that the histopathological classification system ger CE, et al: Towards a clinico-pathological classification of for MTS recognizes 2 main groups—MTS Type 1a and granule cell dispersion in human mesial temporal lobe epilep- 1b (grouped in hippocampal sclerosis [HS] Type 1 in the sies. Acta Neuropathol 117:535–544, 2009 latest HS classification5)—and 2 atypical variants—MTS 4. Blümcke I, Pauli E, Clusmann H, Schramm J, Becker A, Elger C, et al: A new clinico-pathological classification system for Type 2 and MTS Type 3 with a worse seizure outcome. mesial temporal sclerosis. Acta Neuropathol 113:235–244, Furthermore, in 2009 a classification system for GCP was 3 2007 reported, distinguishing among 3 different histological 5. Blümcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, patterns: 1) no GCP (normal granule cell layer); 2) GCP Bernasconi A, et al: International consensus classification of Type 1 (substantial granule cell loss); and 3) GCP Type hippocampal sclerosis in temporal lobe epilepsy: a Task Force

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report from the ILAE Commission on Diagnostic Methods. aforementioned findings, the conclusion could be made Epilepsia 54:1315–1329, 2013 that the 2 different surgical procedures may produce dif- 6. Blümcke I, Thom M, Aronica E, Armstrong DD, Vinters HV, ferent seizure outcomes. Palmini A, et al: The clinicopathologic spectrum of focal cor- tical dysplasias: a consensus classification proposed by an ad In addition to the pathological substrate, other factors such as major depressive disorder,4 extratemporal corti- hoc Task Force of the ILAE Diagnostic Methods Commission. 3 7 Epilepsia 52:158–174, 2011 cal hypometabolism, and epilepsy duration were also 7. Coras R, Siebzehnrubl FA, Pauli E, Huttner HB, Njunting M, considered as postoperative seizure outcome predictors Kobow K, et al: Low proliferation and differentiation capaci- in TLE. Randomized grouping is essential to alleviate ties of adult hippocampal stem cells correlate with memory outcome biases induced by the aforementioned factors. dysfunction in humans. Brain 133:3359–3372, 2010 As we recommended in our article, well-designed ran- 8. da Costa Neves RS, Jardim AP, Caboclo LO, Lancellotti C, domized trials with a sufficient sample size are needed to Marinho TF, Hamad AP, et al: Granule cell dispersion is not compare SelAH and ATL in terms of seizure outcome, IQ a predictor of surgical outcome in temporal lobe epilepsy with mesial temporal sclerosis. Clin Neuropathol 32:24–30, 2013 scores, memory, language ability, visual deficits, and other 9. Engel J Jr, Van Ness P, Rasmussen TB, Ojemann LM: Outcome complications or adverse effects. with respect to epileptic seizures, in Engel J Jr (ed): Surgical Wen-Han Hu, M.D., Ph.D.1 Treatment of the Epilepsies, ed 2. New York: Raven Press, Chao Zhang, M.D.2 1993, pp 609–621 Kai Zhang, M.D., Ph.D.2 10. Giulioni M, Marucci G, Martinoni M, Volpi L, Riguzzi P, Jian-Guo Zhang, M.D., Ph.D.1,2 Marliani AF, et al: Seizure outcome in surgically treated drug- 1Beijing Neurosurgical Institute resistant mesial temporal lobe epilepsy based on the recent Beijing, China histopathological classifications. Clinical article.J Neurosurg 2Beijing Tiantan Hospital 119:37– 47, 2013 Capital Medical University 11. Hu WH, Zhang C, Zhang K, Meng FG, Chen N, Zhang JG: Beijing, China Selective amygdalohippocampectomy versus anterior tem- poral lobectomy in the management of mesial temporal lobe epilepsy: a meta-analysis of comparative studies. A systematic References review. J Neurosurg 119:1089–1097, 2013 1. Assaf BA, Karkar KM, Laxer KD, Garcia PA, Austin EJ, Bar- 12. Marucci G: Commentary on patterns of hippocampal sclerosis baro NM, et al: source localization as predictors of postsurgical outcome. Epilepsia 52:652–653, and surgical outcome in temporal lobe epilepsy. Clin Neuro­ 2011 (Letter) physiol 115:2066–2076, 2004 13. Marucci G, Giulioni M, Rubboli G, Paradisi M, Fernández M, 2. Bate H, Eldridge P, Varma T, Wieshmann UC: The seizure Del Vecchio G, et al: Neurogenesis in temporal lobe epilepsy: outcome after amygdalohippocampectomy and temporal lo- relationship between histological findings and changes in den- Eur J Neurol 14: Eur J tate gyrus proliferative properties. Clin Neurol Neurosurg bectomy. 90–94, 2007 (Erratum in 115:187–191, 2013 Neurol 14:476, 2007) 14. Marucci G, Rubboli G, Giulioni M: Role of dentate gyrus al- 3. Choi JY, Kim SJ, Hong SB, Seo DW, Hong SC, Kim BT, et terations in mesial temporal sclerosis. Clin Neuropathol 29: al: Extratemporal hypometabolism on FDG PET in temporal 32–35, 2010 lobe epilepsy as a predictor of seizure outcome after temporal 15. Thom M, Blümcke I, Aronica E: Long-term epilepsy-associat- lobectomy. Eur J Nucl Med Mol Imaging 30:581–587, 2003 ed tumors. Brain Pathol 22:350–379, 2012 4. de Araujo Filho GM, Gomes FL, Mazetto L, Marinho MM, 16. Thom M, Liagkouras I, Elliot KJ, Martinian L, Harkness W, Tavares IM, Caboclo LO, et al: Major depressive disorder as McEvoy A, et al: Reliability of patterns of hippocampal sclero- a predictor of a worse seizure outcome one year after surgery sis as predictors of postsurgical outcome. Epilepsia 51:1801– in patients with temporal lobe epilepsy and mesial temporal 1808, 2010 sclerosis. Seizure 21:619–623, 2012 5. Giulioni M, Marucci G, Martinoni M, Volpi L, Riguzzi P, Response: We thank Dr. Giulioni and colleagues for Marliani AF, et al: Seizure outcome in surgically treated drug- their constructive comments on our study. We also agree resistant mesial temporal lobe epilepsy based on the recent with them that pathological substrate is essential to pre- histopathological classifications. Clinical article.J Neurosurg dict seizure outcome after temporal lobe epilepsy (TLE) 119:37– 47, 2013 surgery. However, since pathological results were absent 6. Mackenzie RA, Matheson J, Ellis M, Klamus J: Selective ver- in some studies reported in the literature1,2,8,9 or an FCD sus non-selective temporal lobe surgery for epilepsy. J Clin 6 Neurosci 4:152–154, 1997 diagnosis could not be made in one old study, it was diffi- 7. McIntosh AM, Kalnins RM, Mitchell LA, Fabinyi GC, Briell- cult to extract adequate pathological data from the studies mann RS, Berkovic SF: Temporal lobectomy: long-term sei- included in our meta-analysis. zure outcome, late recurrence and risks for seizure recurrence. In TLE patients, most isolated FCD lesions are lo- Brain 127:2018–2030, 2004 cated in the neocortex, and thus they are rarely found in 8. Renowden SA, Matkovic Z, Adams CB, Carpenter K, Oxbury specimens from patients undergoing selective amygda- S, Molyneux AJ, et al: Selective amygdalohippocampectomy lohippocampectomy (SelAH). This means that isolated for hippocampal sclerosis: postoperative MR appearance. FCD is more likely to be diagnosed in an anterior tem- AJNR Am J Neuroradiol 16:1855–1861, 1995 poral lobectomy (ATL) group than in an SelAH group. 9. Tanriverdi T, Olivier A, Poulin N, Andermann F, Dubeau F: The study by Giulioni et al. suggested that isolated FCD Long-term seizure outcome after mesial temporal lobe epilep- was a poor predictor of seizure outcome in TLE patients.5 sy surgery: corticalamygdalohippocampectomy versus selec- tive amygdalohippocampectomy. J Neurosurg 108:517–524, Our meta-analysis indicated that although it was less fre- 2008 quently performed in patients with isolated FCD, patients undergoing SelAH showed statistically lower odds of be- ing seizure free than those undergoing ATL. Based on the Please include this information when citing this paper: published

788 J Neurosurg / Volume 120 / March 2014 Unauthenticated | Downloaded 09/24/21 09:17 AM UTC Neurosurgical forum online January 10, 2014; DOI: 10.3171/2013.10.JNS132161. Role of subconcussion in repetitive mild traumatic brain in- ©AANS, 2014 jury. A review. J Neurosurg 119:1235–1245, 2013 2. Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson Role of subconcussion and repetitive TBI DA, McLean AJ: Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344:1055– 1056, 1994 To The Editor: Recent publication of an article by 3. Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson Bailes et al.1 (Bailes JE, Petraglia AL, Omalu BI, et al: DA, McLean AJ: Topography of axonal injury as defined by Role of subconcussion in repetitive mild traumatic brain amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma 12:565– injury. A review. J Neurosurg 119:1235–1245, November 572, 1995 2013) caught our eye, as we were dismayed by how they 4. Geddes JF: Primary traumatic brain injury, in Whitwell HL inaccurately represented parts of an article by Smith et (ed): Forensic Neuropathology. London: Edward Arnold, al.10 published last year in Neurosurgery, even though we 2005, pp 94–106 are supportive of the proof-of-concept offered. 5. Geddes JF, Whitwell HL, Graham DI: Traumatic axonal in- The clinical evidence supports the concept of a sub- jury: practical issues for diagnosis in medicolegal cases. Neu­ concussion as well, and that evidence is a cornerstone of ropathol Appl Neurobiol 26:105–116, 2000 6. Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Bailes and colleagues’ idea: The concept of increased Demetriadou K: A new model of diffuse brain injury in rats. neck mass and strength that may diffuse the forces im- Part I: pathophysiology and biomechanics. J Neurosurg 80: parted to the head and brain inside the skull (“slosh”) 291–300, 1994 seems far-fetched. 7. Mihalik JP, Guskiewicz KM, Marshall SW, Greenwald RM, We are not convinced that it is possible to extrapolate Blackburn JT, Cantu RC: Does cervical muscle strength in the research of Smith et al.10 to subconcussed individuals youth ice hockey players affect head impact biomechanics? practicing neck-strengthening exercises, all the more so as Clin J Sport Med 21:416–421, 2011 7 8. Miyauchi T, Wei EP, Povlishock JT: Therapeutic targeting of this idea was not supported by the work of Mihalik et al. the axonal and microvascular change associated with repeti- Smith et al. conducted research on rats, and the brain tive mild traumatic brain injury. J Neurotrauma 30:1664– injury they caused in their experiments was of a greater 1671, 2013 magnitude than that seen in the human subjects with sub- 9. Pfister BJ, Iwata A, Meaney DF, Smith DH: Extreme stretch concussion as reported by Bailes et al. This flaw could growth of integrated axons. J Neurosci 24:7978–7983, 2004 be highlighted even more by the argument that the model 10. Smith DW, Bailes JE, Fisher JA, Robles J, Turner RC, Mills suggested by Bailes et al. was introduced by Marmarou JD: Internal jugular vein compression mitigates traumatic axo- 6 nal injury in a rat model by reducing the intracranial slosh ef- et al. to induce diffuse axonal injury (DAI) in rats. DAI fect. Neurosurgery 70:740–746, 2012 is on the most severe end of the traumatic axonal injury 5 11. Tomei G, Spagnoli D, Ducati A, Landi A, Villani R, Fuma- spectrum. The mildest end of the spectrum includes re- galli G, et al: Morphology and neurophysiology of focal axonal versible axonal injury.8,11 A range of injuries that lies in the injury experimentally induced in the guinea pig optic nerve. middle of the spectrum, and for which we do not know the Acta Neuropathol 80:506–513, 1990 clinical correlates, falls short of DAI in severity.2,3 On the other hand, sometimes clues in a patient’s history strongly indicate that DAI was present despite a lack of evidence Response: We appreciate the comments of Drs. Sosa of hematoma or severe brain swelling on imaging studies. and Stemberga concerning our article and will address By systematically studying the of individuals their concerns over neck strengthening and the phenom- who suffered a recent documented mild head injury but enon of brain slosh. We agree that there is no scientific died of an unrelated cause, some authors4,9 have identi- proof or controlled studies that demonstrate that neck fied scattered, hemispherically distributed traumatic axo- strengthening is an effective strategy for reduction of nal damage after mild head injury in patients without any brain injury or the effects of subconcussive impacts. There noteworthy neurological or psychological symptoms. are several aspects, including static muscle contraction, Be that as it may, the literature suggests that extreme player anticipation, gender differences, and the ability of forces are necessary for axons to rupture soon after im- an athlete to control sudden neck movements, that indeed pact. Precisely for this reason, primary axotomy is unlike- make this an uncertain strategy for concussion mitiga- 1 ly to be present in patients who suffer concussion and have tion. Nonetheless, some disciplines, such as in aerospace, completely normal neurological function. have encouraged pilots to perform strengthening exercises 3 Ivan Sosa, M.D. for the neck to help control sudden head movements. Valter Stemberga, M.D., Ph.D. We are familiar with the concepts of intracranial Rijeka University Medical Faculty slosh, as the original work was performed in our laborato- Rijeka, Croatia ry. 4,5 Since mild traumatic brain injury results from crani- al impacts, a theory of brain slosh contends that the forces Disclosure imparted to the outside of the skull cannot be interpreted without understanding how slosh dynamics translate in- The authors report no conflict of interest. side the skull. In this regard, we believe that there are 2 arguments to support neck strengthening. The first is that through better tethering of the cranium, through the con- References traction of stronger cervical musculature on both sides, 1. Bailes JE, Petraglia AL, Omalu BI, Nauman E, Talavage T: the imparted forces may be converted from rotational

J Neurosurg / Volume 120 / March 2014 789 Unauthenticated | Downloaded 09/24/21 09:17 AM UTC Neurosurgical forum to less injurious linear vectors. Also, tensing, toning, or of an athlete to realize the sudden need for neck muscle thickening the neck musculature could aid in the mere act contraction and the timing of such a maneuver is another of shortening the arc or rotational distance through which matter. The above notwithstanding, the concept of neck the head undergoes acceleration-deceleration. If the cra- strengthening to mitigate the forces transmitted to the hu- nium is translated along the path of a straight line, the man brain has not been proven and thus remains a simple distance traveled is relatively less than that along an arc. suggestion for athletic training that should cause no harm, The second argument involves the potential for neck and may, in certain instances, eventually be shown to have musculature strengthening to potentiate the actions of the some benefit. omohyoid muscles as they impede internal jugular venous Julian E. Bailes, M.D. outflow. The omohyoid is an elongated, thin muscle that is NorthShore University HealthSystem directed obliquely in the anterolateral region of the neck, University of Chicago Pritzker School of Medicine extending from the superior edge of the scapula to the Evanston, IL hyoid bone. It is composed of 2 fleshy portions, the an- terior and posterior bellies, separated by an intermediate References tendon. One might question why teleologically there are 2 bellies, with a tendon situated directly atop the internal 1. Mihalik JP, Guskiewicz KM, Marshall SW, Greenwald RM, jugular vein (IJV). This little-understood muscle was once Black­burn JT, Cantu RC: Does cervical muscle strength in youth ice hockey players affect head impact biomechanics? thought to be just an evolutionary vestige and to serve no Clin J Sport Med 21:416–421, 2011 actual purpose. However, we have postulated that the true 2. Patra P, Gunness TK, Robert R, Rogez JM, Heloury Y, Le Hur function of this muscle may be to gently and efficiently po- PA, et al: Physiologic variations of the internal jugular vein tentiate the impedance of outflow by contracting against surface, role of the omohyoid muscle, a preliminary echo- the IJVs, thus reducing slosh within the cranium. In doing graphic study. Surg Radiol Anat 10:107–112, 1988 so, the compliance of the intracranial space would thus be 3. Seng KY, Lam PM, Lee VS: Acceleration effects on neck mus- minimized and, like the inflating of “bubble wrap,” the cle strength: pilots vs. non-pilots. Aviat Space Environ Med brain will be better “packaged” from the inside. In the 74:164–168, 2003 4. Smith DW, Bailes JE, Fisher JA, Robles J, Turner RC, Mills Smith et al. study, significant impact forces were impart- JD: Internal jugular vein compression mitigate traumatic axo- ed, and it was found that there was a marked reduction in nal injury in rat model by reducing intracranial slosh effect. 4 the signature axonal injury with IJV compression. Neurosurgery 70:740–746, 2012 The contraction of the omohyoids has been shown 5. Turner RC, Naser ZJ, Bailes JE, Smith DW, Fisher JA, Rosen by echographic study to cause IJV compression.2 Thus, CL: Effect of slosh mitigation on histologic markers of trau- neck strengthening and training could make the omohy- matic brain injury. Laboratory investigation. J Neurosurg 117: oids more efficient in restricting the outflow of the IJV. 1110–1118, 2012 The omohyoid muscle leads to a direct localized and short compression of IJV, and this in spite of possible diffuse compression by the sternocleidomastoid muscle. The lat- Please include this information when citing this paper: published ter can compress all the vascular elements of the neck it online January 17, 2014; DOI: 10.3171/2013.10.JNS132097. overlies, whatever the position of the head. The ability ©AANS, 2014

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