Phosphohistone H3

Phosphohistone H3

Histone H3 is a nuclear core histone protein of DNA chromatin, with an important role in chromosome condensation and cell cycle progressionduring mitosis and meiosis after phosphorylation of serine-10 and serine-28 residues. Phosphorylation occurs during late G2 to early prophase, while dephosphorylation occurs slowly from late anaphase to early telophase. Therefore in metaphase, histone H3 is always heavily phosphorylated and positive for PHH3, whereas interphase does not or minimally express PHH3 – a property that allows PHH3 to stain only mitotically active cells, therefore proliferation-specific.

PHH3 has been verified in multiple studies concerning various tumors (colorectal adenocarcinoma, ovarian serous adenocarcinoma, pulmonary neuroendocrine carcinoma, uterine smooth muscle tumors, astrocytomas, and meningiomas), for its sensitive and specific role as a marker of mitotic figures (MFs) and excellent correlation with outcome

Histone H3 phosphorylation on serine-10 is specific to mitosis and phosphorylated histone H3 (PHH3) proliferation markers (as counts defined per area or as indices defined per cell numbers) are increasingly being used to evaluate proliferation in various tumors.


Medical records were retrospectively reviewed for all intracranial meningioma cases which diagnosed and underwent surgery at Bezmialem Vakif University Hospital between 2012 and 2017. All World health organization grade 1 meningioma and World health organization grade 2 meningiomapatients constituted the core sample for this study.

This series included 104 (69 female, 35 male) patients, with a median age of 57.3 years. The mean preoperative course was 23.0 ± 40.5 months. The most common symptom was headache (76%) and followed by seizure (24%), weakness (18%) and visual disturbances (14%). Seventy one (68.2%) patients were diagnosed as WHO grade I meningioma and 33 (31.8%) were WHO grade II, World health organization grade 3 meningiomas were excluded from study due to small number of patients. Subtypes of meningioma includes 5 angiomatous meningioma (4,8%), 6 fibroblastic meningioma (5.7%), 1 meningothelial meningioma (0,9%), 11 psammomatous meningioma (10,5%), 3 secretory meningioma (2,8%), 43 transitional meningioma (41,3%) and 33 atypical meningiomas (31,7%). There is a strong correlation with Phosphohistone H3 (PHH-3) and Ki-67(p:0,001>) and mitosis index (p:0,001 > ) although there is no correlation with STAT3 (p:0,260). There is a strong correlation with STAT-3 and Ki-67 (p:0,013), although there is no correlation with mitosis index (p:0,085) and PHH-3 (p:0,260).

In the study they also obtain same results with Ki-67 and mitotic index, although correlation with PHH-3 and STAT-3 is firstly determined and there was no statistically significant relation were observed. Depends on the STAT-3 cell proliferation feature, inactivation of these pathways may predict new chemotherapies for grade II meningiomas 1).


Elmaci et al. from the Department of Neurosurgery, Memorial Hospital, Sisli, Istanbul, Turkey, review data on PHH3 proliferation markers in meningeal tumors. PHH3-staining highlights mitotic cells and makes easier of rapid grading by driving pathologist’s attention on the most mitotically active areas. Thereby, it would function more sensitive in detecting MFs that might be otherwise overloked and more precise by reducing interobserver variability through allowing the pathologist to analyze if the stained nuclei exhibit morphologic features of mitosis 2).

References

1)

Ozek E, Akdag H, Tosuner Z, Abdallah A, Hatiboglu MA. The correlation between phosphorylated Histone H3 (PHH3) and p-STAT3 in Meningiomas. Clin Neurol Neurosurg. 2019 Jan 25;178:46-50. doi: 10.1016/j.clineuro.2019.01.016. [Epub ahead of print] PubMed PMID: 30710729.
2)

Elmaci İ, Altinoz MA, Sari R, Bolukbasi FH. Phosphorylated Histone H3 (PHH3) as a Novel Cell Proliferation Marker and Prognosticator for Meningeal Tumors: A Short Review. Appl Immunohistochem Mol Morphol. 2017 Aug 2. doi: 10.1097/PAI.0000000000000499. [Epub ahead of print] PubMed PMID: 28777144.

Clivus chordoma

Clivus chordoma

www.nature.com_eye_journal_v17_n3_images_6700339f2.jpg

Arising from the embryonic rests of the notochordal, clivus chordoma are slow-growing yet aggressively invasive and destructive tumors.

Types

Poorly differentiated chordoma with SMARCB1/INI1 loss: a distinct molecular entity with dismal prognosis 1).

Clinical features

The most common presenting symptoms of clivus chordoma are headachediplopiadysphagia and dysarthria, and facial sensory changes 2).

Differential diagnosis

Solitary non-chordomatous lesions of the clivus are rare pathologies, which represent a diagnostic challenge.

Imaging features, although mainly specific, are not always diagnostic.

Solitary non-chordomatous lesions of the clival bone are more prevalent than expected. They should be approached with a correct differential diagnosis, considering specific epidemiological, radiological, and histopathological characteristics, to minimise diagnostic bias and allow the planning of the best treatment strategy 3).

see Clivus meningioma.

see Clival metastases.

Degenerative Pannus 4).

Treatment

The management of chordomas of the base of the skull is particularly challenging as they lie adjacent to vital anatomic structures, such as the carotid and basilar arteries and the brain stem, which limits surgical access and resectability as well as delivery of high doses of radiation 5) 6).

The transnasal and transclival approach is for many chordomas a feasible and safe surgical access 7) 8) 9)

Larger tumors, especially those with extensive intradural retrochiasmal and/or deep cervical expansion, are most often resected by open craniotomy. A large number of transcranial approaches have been described in the last decade 10) 11) 12)

Staged procedures are also commonly used in the case of expansive tumor growth.

Koechlin et al. present the first case of a single-session combined transnasal and transcranial approach to radically resect a large clival chordoma.13).

see Endoscopic transnasal transclival approach

see Lateral transcondylar approach

Outcome

They show a strong tendency for local recurrence even after combined surgical and radiosurgical treatment. The possibility of spreading to distant locations of the neuraxis may further complicate the treatment and causes additional morbidity.

A Retrospective review of clival chordomas treated from 1993 to 2013.

Fifty patients (56% male) with median age of 59 years (range, 8-76) were newly diagnosed with clival chordoma of mean diameter 3.3 cm (range, 1.5-6.7). Symptoms included headaches (38%), diplopia (36%), and dysphagia (14%). Procedures included transsphenoidal (n = 34), transoral (n = 4), craniotomy (n = 5), and staged approaches (n = 7). Gross total resection (GTR) rate was 52%, with 83% mean volumetric reduction, values that improved over time. While the lower third of the clivus was the least likely superoinferior zone to contain tumor (upper third = 72%/middle third = 82%/lower third = 42%), it most frequently contained residual tumor (upper third = 33%/middle third = 38%/lower third = 63%; P < .05). Symptom improvement rates were 61% (diplopia) and 53% (headache). Postoperative radiation included proton beam (n = 19), cyberknife (n = 7), intensity-modulated radiation therapy (n = 6), external beam (n = 10), and none (n = 4). At last follow-up of 47 patients, 23 (49%) remain disease-free or have stable residual tumor. Lower third of clivus progressed most after GTR (upper/mid/lower third = 32%/41%/75%). In a multivariate Cox proportional hazards model, male gender (hazard ratio [HR] = 1.2/P = .03), subtotal resection (HR = 5.0/P = .02), and the preoperative presence of tumor in the middle third (HR = 1.2/P = .02) and lower third (HR = 1.8/P = .02) of the clivus increased further growth or regrowth, while radiation modality did not.

The findings underscore long-standing support for GTR as reducing chordoma recurrence. The lower third of the clivus frequently harbored residual or recurrent tumor, despite staged approaches providing mediolateral (transcranial + endonasal) or superoinferior (endonasal + transoral) breadth. There was no benefit of proton-based over photon-based radiation, contradicting conventional presumptions 14).

Recurrence of clival chordoma due to seeding along the surgical pathway is an infrequent mechanism of treatment failure, with only rare cases documented in the literature. When deciding on the appropriate surgical approach, the surgeon must consider the risk of septal seeding during a transseptal approach. The emergence of transnasal endoscopic skull base approaches may reduce the likelihood of surgical pathway tumor seeding 15).

Meta analysis

A systematic search of the literature was done by Labidi et al. in March 2016 using EMBASE and PubMed for articles published between January 2006 and March 2016 to identify surgical series of clivus chordomas. Only articles describing chordomas cases arising from the clivus of craniocervical junction were included in the analysis.

Twenty-seven articles were included in this systematic review, amounting to a total of 1050 patients. The weighted mean rate of GTR was 39.9% (range 0-78.3%) in this patient population. The surgical approaches were described in 16 papers, with 6 series reporting on surgeries done exclusively through the midline corridor (116 patients). In the remaining 10 series (495 patients), the anterior midline approach (AMA) was used in a mean of 56.8% of cases. In studies including patients operated solely through an AMA, a higher GTR rate was obtained (60.7% vs. 42.0%). Postoperative complications were also different between the two cohorts, with lower cranial nerves deficits and CNS infections but higher incidence of CSF leak in the AMA group than in mixed surgical series. In a weighted mean follow-up time of 52.1±21.9 months, recurrences were observed in 38.2% of the total population of patients. Among 423 patients, the weighted 5-year PFS was 49.9±12.1% and the 5-year OS was 73.9±11.2% (N.=391). A random effects model was performed, combining data from studies reporting recurrence rates in GTR and non-GTR (N.=610), with a total odds ratio of having a recurrence for patients who had GTR vs non-GTR of 0.289 (95CI 0.184-0.453).

In this systematic review and meta-analysis of studies published in the last decade, an estimated 5-year PFS of 49.9% and 5-year OS of 73.9% were obtained. The weighted mean GTR rate in the included study was 39.9%, with a significantly reduced occurrence of recurrence in complete resections. Although anterior midline approaches may allow for higher GTR rates and fewer neurological morbidity than traditional transcranial routes, their impact of long-term survival and disease control remains largely unknown 16).

Case series

Data for 12 consecutive patients underwent GKS for post-operative residual histologically verified clival chordoma at the Department of Neurosurgery and Gamma Knife Center, International Medical Center (IMC), 42km. Ismailia Desert Road, Cairo, Egypt from 2006 through end of 2017 were retrospectively reviewed and analyzed with mean follow-up period of 45 months (range12-120 months).

In the last follow up MR, tumor growth control was achieved in 33.3% of patients (mean treated tumors volume was 2.7cc with mean peripheral prescription dose of 16 Gy), and 66.7% of patients reported lost tumor growth control (mean treated tumor volume was 9.2 cc with mean peripheral dose was 13.5 Gy). The overall tumor free progression with mean follow up period of 45mos was 33.3%. The Actuarial 2, 3 and 5 year tumor control rates after initial GKS was 35%, 30% and 25% respectively.

Without satisfactory maximum tumor reduction and sufficient high peripheral prescription radiation tumor dose, it should not be expected that GKS could efficiently control the progression of residual clival chordoma, especially for long term 17).


14 consecutive clivus chordoma cases undergoing maximum surgical resection followed by intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB), using the institutional protocol from the Gangnam Severance Hospital, Seoul, Korea, between 2005 and 2013. Total and near-total resections were achieved in 11 patients (78.6 %), partial in 2 patients (14.3 %), and 1 patient (7.1 %) received RT for recurrent tumor after total resection. Gross residual or the high-risk area defined the planning target volume (PTV)1; PTV2 was the postoperative tumor bed plus a 3-5-mm margin, and PTV3 was PTV2 plus a 5-10 mm margin. A moderate hypofractionation schedule was used: doses to PTV1, PTV2 and PTV3 were 3.9 Gy, 3.15 Gy and 2.8 Gy through 15 fractions for the first two patients, and the rest received 2.5 Gy, 2.2 Gy and 1.8 Gy through 25 fractions. The biologically equivalent dose in 2-Gy fractions (EQD2) was 65-68 Gy for PTV1, 52-56 Gy for PTV2, and 44.3-44.8 Gy for PTV3.

Median follow-up was 41 months. Eight patients were free of disease for median 42.5 months (range 23-91 months), four patients had stable disease for median 60.5 months (range 39-113 months), and 1 patient showed partial response for 38 months after RT. Local progression was seen in one patient who received EQD2 67.8 Gy after partial resection. Estimated 5-year progression-free and overall survival rates were 92.9 %. Surgery improved the neurologic deficit in six patients, and IMRT-SIB was well tolerated without lasting toxicity.

The experience suggests that maximum resection and high-dose IMRT-SIB can achieve local control without significant morbidities 18).

Case reports

2017

Cha et al. report two cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression, which is very rare among the pediatric chordoma types. Both patients presented clival masses on preoperative MRI. Histologically, both tumors had nonclassic histologic features for conventional chordoma: sheets of large epithelioid to spindle cells with vesicular nuclei and prominent nucleoli. Both cases revealed nuclear expression of brachyury, loss of SMARCB1/INI1 expression and lack of embryonal, neuroectodermal, or epithelial component. One case showed heterozygous loss of EWSR1 gene by break-apart fluorescence in situ hybridization that reflected loss of SMARCB1/INI1 gene. Based on the clival location and histologic findings along with the loss of SMARCB1/INI1 expression and positivity for nuclear brachyury staining, the final pathologic diagnosis for both cases was PD chordoma 19).


In the Department of Neurosurgery, Austin Hospital, Heidelberg, Victoria, Australia, a case of a 25 year-old male patient with chordoma in the inferior clivus which was initially debulked via a transnasal endoscopic approach. He unfortunately had a large recurrence of tumor requiring re-do resection. With the aim to achieve maximal surgical resection, we then chose the technique of a transoral approach with Le Fort 1 maxillotomy and midline palatal split. Post-operative course for the patient was uneventful and post-operative MRI confirmed significant debulking of the clival lesion. The technique employed for the surgical procedure is presented here in detail as is our experience over two decades using this technique for tumors, inflammatory lesions and congenital abnormalities at the cranio-cervical junction 20).

References

1) , 19)

Cha YJ, Hong CK, Kim DS, Lee SK, Park HJ, Kim SH. Poorly differentiated chordoma with loss of SMARCB1/INI1 expression in pediatric patients: A report of two cases and review of the literature. Neuropathology. 2017 Aug 15. doi: 10.1111/neup.12407. [Epub ahead of print] PubMed PMID: 28812319.
2)

Harbour JW, Lawton MT, Criscuolo GR, Holliday MJ, Mattox DE, Long DM. Clivus chordoma: a report of 12 recent cases and review of the literature. Skull Base Surg. 1991;1(4):200-6. PubMed PMID: 17170837; PubMed Central PMCID: PMC1656331.
3)

Gagliardi F, Spina A, Boari N, Narayanan A, Mortini P. Solitary lesions of the clivus: what else besides chordomas? An extensive clinical outlook on rare pathologies. Acta Neurochir (Wien). 2015 Apr;157(4):597-605. doi: 10.1007/s00701-014-2340-1. Epub 2015 Jan 16. PubMed PMID: 25591803.
4)

Khaldi A, Griauzde J, Duckworth EA. Degenerative Pannus Mimicking Clival Chordoma Resected via an Endoscopic Transnasal Approach. Skull Base Rep. 2011 May;1(1):7-12. doi: 10.1055/s-0031-1275243. Epub 2011 Mar 30. PubMed PMID: 23984195; PubMed Central PMCID: PMC3743584.
5)

Austin JP, Urie MM, Cardenosa G, Munzenrider JE. Probable causes of recurrence in patients with chordoma and chondrosarcoma of the base of skull and cervical spine. Int J Radiat Oncol Biol Phys 1993;25:439-444
6)

Castro JR, Linstadt DE, Bahary JP, et al. Experience in charged particle irradiation of tumors of the skull base: 1977–1992. Int J Radiat Oncol Biol Phys 1994;29:647-655
7)

Holzmann D, Reisch R, Krayenbühl N, Hug E, Bernays R L. The transnasal transclival approach for clivus chordoma. Minim Invasive Neurosurg. 2010;53(5–6):211–217.
8)

Saito K, Toda M, Tomita T, Ogawa K, Yoshida K. Surgical results of an endoscopic endonasal approach for clival chordomas. Acta Neurochir (Wien) 2012;154(5):879–886.
9)

Fraser J F Nyquist G G Moore N Anand V K Schwartz T H Endoscopic endonasal minimal access approach to the clivus: case series and technical nuances Neurosurgery 2010. 673, (Suppl Operative):ons150–ons158.ons158; discussionons158
10)

Crumley R L, Gutin P H. Surgical access for clivus chordoma. The University of California, San Francisco, experience. Arch Otolaryngol Head Neck Surg. 1989;115(3):295–300.
11)

Harbour J W, Lawton M T, Criscuolo G R, Holliday M J, Mattox D E, Long D M. Clivus chordoma: a report of 12 recent cases and review of the literature. Skull Base Surg. 1991;1(4):200–206.
12)

Sen C, Triana A I, Berglind N, Godbold J, Shrivastava R K. Clival chordomas: clinical management, results, and complications in 71 patients. J Neurosurg. 2010;113(5):1059–1071.
13)

Koechlin NO, Simmen D, Briner HR, Reisch R. Combined transnasal and transcranial removal of a giant clival chordoma. J Neurol Surg Rep. 2014 Aug;75(1):e98-e102. doi: 10.1055/s-0034-1373668. Epub 2014 May 28. PubMed PMID: 25083400; PubMed Central PMCID: PMC4110148.
14)

Jahangiri A, Chin AT, Wagner JR, Kunwar S, Ames C, Chou D, Barani I, Parsa AT, McDermott MW, Benet A, El-Sayed IH, Aghi MK. Factors predicting recurrence after resection of clival chordoma using variable surgical approaches and radiation modalities. Neurosurgery. 2015 Feb;76(2):179-86. doi: 10.1227/NEU.0000000000000611. PubMed PMID: 25594191.
15)

Hines JP, Ashmead MG, Stringer SP. Clival chordoma of the nasal septum secondary to surgical pathway seeding. Am J Otolaryngol. 2014 Jan 2. pii:S0196-0709(13)00301-3. doi: 10.1016/j.amjoto.2013.12.018. [Epub ahead of print]PubMed PMID: 24480512.
16)

Labidi M, Watanabe K, Bouazza S, Bresson D, Bernat AL, George B, Froelich S. Clivus chordomas: a systematic review and meta-analysis of contemporary surgical management. J Neurosurg Sci. 2016 Dec;60(4):476-84. PubMed PMID: 27303859.
17)

Hafez RFA, Fahmy OM, Hassan HT. Gamma knife surgery efficacy in controlling postoperative residual clival chordoma growth. Clin Neurol Neurosurg. 2019 Jan 25;178:51-55. doi: 10.1016/j.clineuro.2019.01.017. [Epub ahead of print] PubMed PMID: 30710730.
18)

Kim JW, Suh CO, Hong CK, Kim EH, Lee IJ, Cho J, Lee KS. Maximum surgical resection and adjuvant intensity-modulated radiotherapy with simultaneous integrated boost for skull base chordoma. Acta Neurochir (Wien). 2016 Aug 9. [Epub ahead of print] PubMed PMID: 27502775.
20)

Abdul Jalil MF, Story RD, Rogers M. Extended maxillotomy for skull base access in contemporary management of chordomas: Rationale and technical aspect. J Clin Neurosci. 2017 Feb 19. pii: S0967-5868(16)30694-4. doi: 10.1016/j.jocn.2017.01.031. [Epub ahead of print] PubMed PMID: 28228324.

Obesity in neurosurgery

Obesity in neurosurgery

Concern exists for increased complications due to surgical challenges posed by obese patients and their often-prevalent comorbidities.

In a study involving a nationwide administrative database, milder obesity was not significantly associated with increased mortality rates, neurological complications, or poor outcomes after SAH. Morbid obesity, however, was associated with increased odds of venous thromboembolic, renal, and infectious complications, as well as of a nonroutine hospital discharge. Notably, milder obesity was associated with decreased odds of some medical complications, primarily in patients treated with coiling 1).

Obesity is a major risk factor globally and it is associated with an increased risk of severe vision loss due to idiopathic intracranial hypertension(IIH). There has been an increase in obesity prevalence in the Middle East countries mainly affecting the Gulf Council Countries (GCC), which parallels increased industrial development. This rise may be contributing to the increasing incidence of IIH in these countries. Other risk factors may also be contributing to IIH in Middle East countries and the differences and similarities to Western IIH merit further study 2).


Li et al., from Beijing aimed to examine the relationship between metabolically healthy obese (MHO) and risk of cardiovascular diseases (CVD) among the Chinese population.

The China Health and Retirement Longitudinal Study is a prospective cohort study of 7849 participants aged ≥45 years without CVD at baseline. Metabolic health status was assessed based on blood pressuretriglycerides, high-density lipoprotein cholesterol, glycated hemoglobin, fasting glucose, and C reactive protein. A cutoff point of body mass index of 24.0 kg/m2 was used to define over-weight/obesity (≥24.0 kg/m2) or normal weight (<24.0 kg/m2). CVD was based on self-reported doctor’s diagnosis of heart problems and stroke. Incidence rate ratio (IRR) with 95% confidence interval (CI) was deduced from modified Poisson regression.

During a mean 3.6 years of follow-up, 880 incident CVD events were recorded. 789 (10.05%) were identified MHO among 3321 (42.3%) obese individuals. Compared with metabolically healthy normal weight individuals, the multivariable adjusted IRR of CVD was 1.33 (95%CI: 1.19-1.49) for MHO, 1.29 (95%CI: 1.22-1.38) for metabolically unhealthy normal weight, and 1.61 (95%CI: 1.51-1.75) for metabolically unhealthy obese in the full adjusted model.

MHO individuals are associated with the increased risk of cardiovascular diseases among the Chinese population 3).

Types

see Hypothalamic obesity.

Severe obesity: body mass index (BMI ≥ 35).

Obesity in spinal surgery

Deep brain stimulation for obesity

Sixteen Sprague-Dawley rats were maintained on a high-fat diet. Daily food intake and weight gain were measured for 7 days, at which time the animals underwent stereotactic placement of 0.25-mm-diameter bipolar stimulating electrodes bilaterally in the LH. On postoperative Day 7, eight animals began to receive continuous stimulation of the LH. The remaining eight animals were left unstimulated as the control group. Individual animal weight, food intake, and water intake were monitored daily and continuously throughout the experiment until postoperative Day 24.

There was a decreased rate of weight gain after surgery in all animals, but the unstimulated group recovered and resumed a linear weight gain curve. The stimulated group, however, failed to show weight gain and remained below the mean baseline for body mass. There was a significant weight loss between the stimulated and unstimulated groups. On postoperative Day 24, compared with the day of surgery (Day 0), the unstimulated group had a mean weight gain of 13.8%, whereas the stimulated group had a 2.3% weight loss on average (p = 0.001), yielding a 16.1% weight difference between the two groups 4).


The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the brain’s reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control5).


Several studies have shown involvement of the nucleus accumbens in these and other addictive behaviors. In a case report, a patient who quit smoking and lost weight without any effort.

A 47-year-old woman presented with chronic treatment-refractory obsessive-compulsive disorder, nicotine dependence, and obesity.

The patient was treated with deep brain stimulation of the nucleus accumbens for obsessive-compulsive disorder. Unintended, effortless, and simultaneous smoking cessation and weight loss were observed.

This study supports the idea of compulsivity with common circuitry in the processing of diverse rewards and suggests that deep brain stimulation of the nucleus accumbens could be a possible treatment of patients with a dependency not responding to currently available treatments 6).


Deep brain stimulation must achieve a success rate of 83% to be equivalent to bariatric surgery. This high-threshold success rate is probably due to the reported success rate of LRYGB, despite its higher complication rate (33.4%) compared with DBS (19.4%). The results support further research into the role of DBS for the treatment of obesity 7).


Appetite modulation in conjunction with enhancing metabolic rate with hypothalamic lesions has been widely documented in animal and even in humans. It appears these effects can be reproduced by DBS, and the titratability and reversibility of this procedure, in addition to well established safety profile, make DBS an appealing option for obesity treatment. Targeting the hypothalamus with DBS has already been shown to be feasible and potentially effective in managing patients with intractable chronic cluster headache. The surgical risk however must be cautiously taken into account when targeting the hypothalamus, where some mortality cases have been reported when targeting the posterior part. The development of new surgical approach will probably reduce this surgical risk. Moreover, the role of functional neurosurgery in obesity is not a new idea. In fact, LH was targeted in obese humans with electrocoagulation more than 30 years ago, resulting in significant yet transient appetite suppression and slight weight reduction. All those elements have made possible the recent regain of interest in DBS for morbid obesity and open an exciting new area of research in neurosurgery and endocrinology 8).


Ho et al. present a review of the evidence of the neuroanatomical basis for obesity, the potential neural targets for deep brain stimulation (DBS), as well as a rationale for DBS and future trial design. Identification of an appropriate patient population that would most likely benefit from this type of therapy is essential. There are also significant cost and ethical considerations for such a neuromodulatory intervention designed to alter maladaptive behavior. Finally, the authors present a consolidated set of inclusion criteria and study end points that should serve as the basis for any trial of DBS for obesity 9).

Dupré et al. review the history of deep brain stimulation (DBS) in patients for treating obesity, describe current DBS targets in the brain, and discuss potential DBS targets and nontraditional stimulation parameters that may improve the effectiveness of DBS for ameliorating obesity. Deep brain stimulation for treating obesity has been performed both in animals and in humans with intriguing preliminary results. The brain is an attractive target for addressing obesity because modulating brain activity may permit influencing both sides of the energy equation-caloric intake and energy expenditure 10).

Tumor

Findings highlight obesity as a risk factor for overall brain/CNS tumors, meningiomas and gliomas among females, as well as for meningiomas among males 11).

For Niedermaier et al adiposity is related to enhanced risk for meningioma but is unassociated with risk for glioma. Based on a limited body of evidence, physical activity is related to decreased risk of meningioma but shows little association with risk of glioma 12).

References

1)

Dasenbrock HH, Nguyen MO, Frerichs KU, Guttieres D, Gormley WB, Ali Aziz-Sultan M, Du R. The impact of body habitus on outcomes after aneurysmal subarachnoid hemorrhage: a Nationwide Inpatient Sample analysis. J Neurosurg. 2016 Jul 15:1-11. [Epub ahead of print] PubMed PMID: 27419827.
2)

Almarzouqi SJ, Morgan ML, Lee AG. Idiopathic intracranial hypertension in the Middle East: A growing concern. Saudi J Ophthalmol. 2015 Jan-Mar;29(1):26-31. doi: 10.1016/j.sjopt.2014.09.013. Epub 2014 Sep 28. Review. PubMed PMID: 25859136; PubMed Central PMCID: PMC4314590.
3)

Li H, He D, Zheng D, Amsalu E, Wang A, Tao L, Guo J, Li X, Wang W, Guo X. Metabolically healthy obese phenotype and risk of cardiovascular disease: Results from the China Health and Retirement Longitudinal Study. Arch Gerontol Geriatr. 2019 Jan 25;82:1-7. doi: 10.1016/j.archger.2019.01.004. [Epub ahead of print] PubMed PMID: 30710843.
4)

Sani S, Jobe K, Smith A, Kordower JH, Bakay RA. Deep brain stimulation for treatment of obesity in rats. J Neurosurg. 2007 Oct;107(4):809-13. PubMed PMID: 17937228.
5)

Halpern CH, Wolf JA, Bale TL, Stunkard AJ, Danish SF, Grossman M, Jaggi JL, Grady MS, Baltuch GH. Deep brain stimulation in the treatment of obesity. J Neurosurg. 2008 Oct;109(4):625-34. doi: 10.3171/JNS/2008/109/10/0625. Review. PubMed PMID: 18826348.
6)

Mantione M, van de Brink W, Schuurman PR, Denys D. Smoking cessation and weight loss after chronic deep brain stimulation of the nucleus accumbens: therapeutic and research implications: case report. Neurosurgery. 2010 Jan;66(1):E218; discussion E218. doi: 10.1227/01.NEU.0000360570.40339.64. PubMed PMID: 20023526.
7)

Pisapia JM, Halpern CH, Williams NN, Wadden TA, Baltuch GH, Stein SC. Deep brain stimulation compared with bariatric surgery for the treatment of morbid obesity: a decision analysis study. Neurosurg Focus. 2010 Aug;29(2):E15. doi: 10.3171/2010.5.FOCUS10109. Review. PubMed PMID: 20672917.
8)

Torres N, Chabardès S, Benabid AL. Rationale for hypothalamus-deep brain stimulation in food intake disorders and obesity. Adv Tech Stand Neurosurg. 2011;36:17-30. doi: 10.1007/978-3-7091-0179-7_2. Review. PubMed PMID: 21197606.
9)

Ho AL, Sussman ES, Pendharkar AV, Azagury DE, Bohon C, Halpern CH. Deep brain stimulation for obesity: rationale and approach to trial design. Neurosurg Focus. 2015 Jun;38(6):E8. PubMed PMID: 26030708.
10)

Dupré DA, Tomycz N, Oh MY, Whiting D. Deep brain stimulation for obesity: past, present, and future targets. Neurosurg Focus. 2015 Jun;38(6):E7. PubMed PMID: 26030707.
11)

Sergentanis TN, Tsivgoulis G, Perlepe C, Ntanasis-Stathopoulos I, Tzanninis IG, Sergentanis IN, Psaltopoulou T. Obesity and Risk for Brain/CNS Tumors, Gliomas and Meningiomas: A Meta-Analysis. PLoS One. 2015 Sep 2;10(9):e0136974. doi: 10.1371/journal.pone.0136974. eCollection 2015. PubMed PMID: 26332834; PubMed Central PMCID: PMC4558052.
12)

Niedermaier T, Behrens G, Schmid D, Schlecht I, Fischer B, Leitzmann MF. Body mass index, physical activity, and risk of adult meningioma and glioma: A meta-analysis. Neurology. 2015 Sep 16. pii: 10.1212/WNL.0000000000002020. [Epub ahead of print] Review. PubMed PMID: 26377253.
WhatsApp WhatsApp us
%d bloggers like this: