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Book: Complex Surgical Cases of the Limbic System

Complex Surgical Cases of the Limbic System
By Sepehr Sani

Complex Surgical Cases of the Limbic System

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The limbic system (also known as the paleomammalian brain) is a collection of brain structures located in the middle of the brain. It is not a discrete system itself but rather a collection of structures-anatomically related but varying greatly in function. The limbic system is the centre for emotional responsiveness, motivation, memory formation and integration, olfaction, and the mechanisms to keep ourselves safe (Neuropsychotherapist.com). This book is a guide to surgical procedures for the limbic system. Beginning with an overview of brain embryology and anatomy, each of the following sections covers surgical approaches for disorders in different parts of the limbic system. Procedures are explained in a step by step approach, with emphasis on anatomical markers and avoidance of complications. The final chapters discuss brain mapping during surgery, giant and unusual tumours, and vascular lesions. Authored by a team of highly experienced, Illinois and Wisconsin-based neurosurgeons, the book is enhanced by anatomical dissections, operative photographs and illustrations, and includes a DVD ROM demonstrating surgical procedures. Key points * Guide to surgical procedures for the limbic system * Step by step approach with emphasis on anatomical markers and avoidance of complications * Highly experienced, Illinois and Wisconsin-based author team * Includes DVD ROM demonstrating surgical procedures


Product Details

  • Original language: English
  • Dimensions: 9.50″ h x .0″ w x 6.30″ l,
  • Binding: Hardcover
  • 180 pages

Editorial Reviews

About the Author
Sepehr Sani MD Assistant Professor, Department of Neurosurgery, Rush University Medical Centre, Chicago, IL, USA Mustafa K Baskaya MD Department of Neurological Surgery, University of Wisconsin-Madison School of Medicine, Madison, WI, USA Richard W Byrne MD Chairman, Department of Neurosurgery, Rush University Medical Centre, Chicago, IL, USA

Update: A1 segment hypoplasia

Anterior cerebral artery A1 segment hypoplasia is an uncommon fetal variant of the circle of Willis.

There is an association of unilaterally absent or hypoplastic A1 segments of the anterior cerebral artery with ipsilateral decrease in internal carotid artery (ICA) caliber, and this can be seen on MR angiograms 1).

Epidemiology

Hypoplasia of the proximal (A1) segment of the anterior cerebral artery (ACA) was examined in 50 human brains and on 8 selected carotid arteriograms. Hypoplasia has been found in 22% of the cases. Two types of this phenomenon exist, namely the mild and extreme hypoplasia. Mild hypoplasia has been noticed in 14% of the specimens. The hypoplastic vessel has ranged from 1.3 to 1.9 mm in diameter (average 1.6 mm) and it was from 0.6 to 0.9 mm smaller than the opposite A1 portion. Extremely hypoplastic proximal segment has been present in 8% of the cases. It has varied from 0.3 to 1.1 mm in size (average 0.9 mm) and has been more than 1 mm smaller than the opposite proximal segment. Both mild and extreme hypoplasia have been associated in 81.8% of the cases with the corresponding variations or malformations of the anterior cerebral, posterior cerebral, posterior communicating and basilar arteries 2).

The incidence of right-sided A1 segment hypoplasia either accompanied with AcomA aneurysm or not was much greater than that of left-sided. Intracranial AcomA aneurysm development appeared to be associated with A1 segment hypoplasia 3).

Complications

The A1 segment of the anterior cerebral artery is a principal supplier of anterior collateral blood flow.

The aim of a study was to determine whether A1 segment hypoplasia may be responsible for acute ischemic stroke.

Chuang et al. consecutively examined 280 acute ischemic stroke patients (aged 66.9 +/- 14.2 years). Cerebral magnetic resonance angiography was performed within 72 h of ischemic stroke onset. The overall incidence of A1 variation in our experimental group was 15.0% (n = 42, agenesis/hypoplasia = 18/24), which was statistically higher than in the control group (n = 12). The majority (n = 30, 71.42%) had ipsilateral striatal lacunar infarctions. Based on these results, A1 agenesis/hypoplasia appears to be a risk factor contributing to ischemic stroke, especially to strokes in arteries penetrating the striatal area 4).

Yamaguchi et al. report two cases of bilateral anterior cerebral artery (ACA) territory infarction. On magnetic resonance (MR) angiograms, the A1 segment of the ACA was unilaterally hypoplastic in both cases, suggesting that unilateral hypoplasia of A1 is a significant predisposing factor for this rare type of cerebral infarction. When the contralateral A1 is dominant, embolic materials may enter into it more easily 5).


Hypoplasia of the A1 segment of the anterior cerebral artery is frequently observed in patients with anterior communicating artery aneurysms. The effect of this anatomical variant on ACoA aneurysm morphology is not well understood 6).

Case series

2017

Yang et al. retrospectively reviewed 251 patients with ACoA aneurysm who underwent surgical clipping in Beijing Tiantan Hospital between September 2011 and September 2016. Their clinical and radiologic features, as well as clinical outcomes were reviewed. In addition, univariate and multivariate logistic regression analysis was performed to identify independent risk factors for the postoperative infarction and unfavorable clinical outcomes of surgical clipping ACoA aneurysm.

The incidence of A1 segment hypoplasia was 49.8% (125 of 251 patients). Univariate analysis revealed that multiple aneurysm (P=0.025), diameter of aneurysm (P=0.040) and A1 segment hypoplasia (P=0.010) were associated with anterior cerebral artery (ACA) territories infarction, and A1 segment hypoplasia (P=0.002) is significantly correlated with unfavorable clinical outcomes of surgical clipping ACoA aneurysm. Moreover, multivariate analysis showed that multiple aneurysm (P=0.038, OR=2.571), diameter of aneurysm (P=0.034, OR=1.097) and A1 segment hypoplasia (P=0.007, OR=3.619) were strongly independent risk factors for ACA territories infarction. In addition, Hunt and Hess scores (HH) (P=0.036, OR=2.326) and A1 segment hypoplasia (P=0.002, OR=2.873) are significant independent risk factors for unfavorable clinical outcomes of surgical clipping ACoA aneurysm.

A1 segment hypoplasia is a significant independent risk factor for unfavorable clinical outcomes of surgical clipping ACoA aneurysm and ACA infarction after surgery 7).

Case reports

2016

A case of anterior cerebral artery A1 segment hypoplasia syndrome presenting with right lower limb monoplegia, abulia, and urinary incontinence8).

2000

A 68-year-old man presented with a Hunt and Hess Grade II subarachnoid hemorrhage and symptoms of headache, nuchal rigidity, and facial paresis. : Angiographic evaluation with superselective exploration revealed a small ruptured aneurysm located on a duplicated hypoplastic A1 segment of the left anterior cerebral artery with associated middle cerebral artery stenosis and secondary early moyamoya changes. Surgical clipping of the aneurysm was performed successfully while sparing the hypoplastic A1 segment.

A1 aneurysms occurring on a duplicated anterior cerebral artery segment probably develop from a congenital weakness of the parent vessel and increased local shear stress. Superselective angiography was helpful in the preoperative planning and facilitated the decision to treat with surgical clipping instead of embolization 9).

1)

Kane AG, Dillon WP, Barkovich AJ, Norman D, Dowd CF, Kane TT. Reduced caliber of the internal carotid artery: a normal finding with ipsilateral absence or hypoplasia of the A1 segment. AJNR Am J Neuroradiol. 1996 Aug;17(7):1295-301. PubMed PMID: 8871715.
2)

Marinković S, Kovacević M, Milisavljević M. Hypoplasia of the proximal segment of the anterior cerebral artery. Anat Anz. 1989;168(2):145-54. PubMed PMID: 2712326.
3)

Chen H, Li MH. A1 segment hypoplasia accompanied by AcomA aneurysms assessed with magnetic resonance angiography. Surg Radiol Anat. 2014 May;36(4):353-7. doi: 10.1007/s00276-013-1182-5. Epub 2013 Aug 4. PubMed PMID: 23912562.
4)

Chuang YM, Liu CY, Pan PJ, Lin CP. Anterior cerebral artery A1 segment hypoplasia may contribute to A1 hypoplasia syndrome. Eur Neurol. 2007;57(4):208-11. Epub 2007 Jan 19. PubMed PMID: 17268201.
5)

Yamaguchi K, Uchino A, Sawada A, Takase Y, Kuroda Y, Kudo S. Bilateral anterior cerebral artery territory infarction associated with unilateral hypoplasia of the A1 segment: report of two cases. Radiat Med. 2004 Nov-Dec;22(6):422-5. PubMed PMID: 15648459.
6)

Rinaldo L, McCutcheon BA, Murphy M, Bydon M, Rabinstein AA, Lanzino G. 360 Relationship of A1 Segment Hypoplasia to Anterior Communicating Artery Aneurysm Morphology and Risk Factors for Rupture. Neurosurgery. 2016 Aug;63 Suppl 1:207. doi: 10.1227/01.neu.0000489849.55193.67. PubMed PMID: 27399558.
7)

Yang F, Li H, Wu J, Li M, Chen X, Jiang P, Li Z, Cao Y, Wang S. Relationship of A1 segment hypoplasia to the radiological and clinical outcomes of surgical clipping anterior communicating artery aneurysm. World Neurosurg. 2017 Jul 29. pii: S1878-8750(17)31222-6. doi: 10.1016/j.wneu.2017.07.122. [Epub ahead of print] PubMed PMID: 28765030.
8)

Lakhotia M, Pahadiya HR, Prajapati GR, Choudhary A, Gandhi R, Jangid H. A case of anterior cerebral artery A1 segment hypoplasia syndrome presenting with right lower limb monoplegia, abulia, and urinary incontinence. J Neurosci Rural Pract. 2016 Jan-Mar;7(1):189-91. doi: 10.4103/0976-3147.168438. PubMed PMID: 26933381; PubMed Central PMCID: PMC4750332.
9)

Taylor R, Connolly ES Jr, Duong H. Radiographic evidence and surgical confirmation of a saccular aneurysm on a hypoplastic duplicated A1 segment of the anterior cerebral artery: case report. Neurosurgery. 2000 Feb;46(2):482-4. PubMed PMID: 10690739.

Update: Maffucci syndrome

Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome).

Additionally, neuroendocrine tumors including pituitary adenomas have been described in patients with Maffucci syndrome.

The rate of malignant transformation in Maffucci syndrome is high, with enchondromas transforming into chondrosarcomas and the development of secondary neoplasms, including pancreatic and hepatic adenocarcinoma, mesenchymal ovarian tumors, and brain tumors such as glioma. However, hematopoietic malignancies arising in Maffucci syndrome are rare 1)

Etiology

The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2)2).

Case series

2017

Cerebral MRI was routinely performed in Ollier-Maffucci patients followed-up in tertiary centers. Patients with previous history of skull base or intracranial tumors were excluded from the study. Clinical and radiological datas were retrospectively collected. The occurrence rate and nature of abnormal cerebral MRIs were determined.

Twelve patients were included. A glioma-looking lesion was found in one patient (8%), while skull base lesions were evidenced in 3 others (25%). A regular MRI follow-up was recommended for each patient, with a time interval varying between 1year and 3years depending on the likelihood of tumoral evolutivity, as infered from the MRI findings.

All in all, the high rate of intracranial and skull base lesions with a malignant potential warrants to include cerebral MRI in the routine follow-up of Ollier-Maffucci patients 3).

Case report

2016

A report describes a patient with Maffucci syndrome who presented with skull base tumors and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors.

This report provides the first genetic evidence for the inclusion of pituitary adenomas among tumors characterizing Maffucci syndrome. In patients who are newly diagnosed with Maffucci syndrome, it is appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction 4).


A 39-year-old woman who was diagnosed with Maffucci syndrome together with intrahepatic cholangiocarcinoma (IHCC). Heterozygous somatic mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes are associated with a number of different tumor types (e.g. IHCC) and also with Maffucci syndrome. For IHCC, mutations in IDH1/IDH2 are associated with higher survival rates. IHCC tissue as well as normal liver tissue and peripheral blood were analyzed for IDH1/IDH2-mutations in our patient. In the tumor sample, we identified a recurrent somatic IDH1-mutation affecting Arg132, while in normal liver tissue and peripheral blood, no variants were detected, as expected.

This case report presents the second patient in the literature exhibiting the features of Maffucci syndrome along with cholangiocarcinoma. This supports the hypothesis that IDH1/2-mutations, which can be present in different types of tumor tissue simultaneously, arise during embryonic development in a mosaic pattern; as a result, a more aggressive follow-up is proposed in patients with Maffucci syndrome to exclude neoplasms 5).

2009

First case of Maffucci syndrome associated with a pituitary adenoma and a probable brainstem glioma

A 35-year-old woman with Marfucci syndrome (diagnosed when she was 22 years old) who presented with complaints of decreased visual acuity and visual field defect. Neuroimaging revealed a pituitary macroadenoma and a suspected brainstem tumor. The macroadenoma was partially removed. There were no postoperative complications and the patient experienced rapid improvement in visual acuity. On follow-up examination 2 years later, the lesion in the pons showed the same dimensions. No sarcomatous changes of enchondromas or hemangiomas occurred. To the authors’ knowledge, including the present case, only 7 cases of Maffucci syndrome associated with glioma and 7 cases associated with pituitary adenoma have been reported in the literature. This report emphasizes that patients with this disease are at a higher risk for primary intracranial tumors and reinforces the concept of the multiplicity of tumors that may arise in this syndrome. It also underscores the importance of early diagnosis, regular clinical surveillance, and follow-up studies of these patients 6).

1)

Akiyama M, Yamaoka M, Mikami-Terao Y, Ohyama W, Yokoi K, Arakawa Y, Takita J, Suzuki H, Yamada H. Somatic mosaic mutations of IDH1 and NPM1 associated with cup-like acute myeloid leukemia in a patient with Maffucci syndrome. Int J Hematol. 2015 Dec;102(6):723-8. doi: 10.1007/s12185-015-1892-z. Epub 2015 Oct 27. PubMed PMID: 26508204.

2)

Pansuriya TC, van Eijk R, d’Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet. 2011 Nov 6;43(12):1256-61. doi: 10.1038/ng.1004. PubMed PMID: 22057234; PubMed Central PMCID: PMC3427908.

3)

Mandonnet E, Anract P, Martin E, Roujeau T, Spena G, Cormier-Daire V, Duffau H, Baujat G; Collaborators. Brain and skull base MRI findings in patients with Ollier-Maffucci disease: A series of 12 patient-cases. Clin Neurol Neurosurg. 2017 Jul 18;160:147-151. doi: 10.1016/j.clineuro.2017.07.011. [Epub ahead of print] PubMed PMID: 28750360.

4)

Hao S, Hong CS, Feng J, Yang C, Chittiboina P, Zhang J, Zhuang Z. Somatic IDH1 mutation in a pituitary adenoma of a patient with Maffucci syndrome. J Neurosurg. 2016 Jun;124(6):1562-7. doi: 10.3171/2015.4.JNS15191. Epub 2015 Oct 16. PubMed PMID: 26473790.

5)

Prokopchuk O, Andres S, Becker K, Holzapfel K, Hartmann D, Friess H. Maffucci syndrome and neoplasms: a case report and review of the literature. BMC Res Notes. 2016 Feb 27;9(1):126. doi: 10.1186/s13104-016-1913-x. PubMed PMID: 26920730; PubMed Central PMCID: PMC4769492.

6)

Ruivo J, Antunes JL. Maffucci syndrome associated with a pituitary adenoma and a probable brainstem tumor. J Neurosurg. 2009 Feb;110(2):363-8. doi: 10.3171/2008.8.JNS08150. Review. PubMed PMID: 18976063.

Update: Amelanotic melanoma

Primary amelanotic melanoma is a special subtype of Primary melanocytic neoplasm, which is especially rare.

Very few cases of amelanotic variation of primary melanoma in the CNS were reported on. General guidelines or recommendations to establish this diagnosis do not exist.

Sun et al. established intracranial and subcutaneous melanoma models using cultured malignant cells derived from amelanotic melanoma. The median survival times in a mouse model with intracranial tumors was 20 days, but a mouse model with subcutaneous tumors did not show cachexia until they were killed 28 days after inoculation with tumor cells. Histopathological analysis showed that a high karyokinesis phase and nuclear pleomorphism appeared in the intracranial model compared with the subcutaneous tumor model mice. The tumor boron concentration at 2.5 h after boronophenylalanine administration was 15.21±3.88 μg/g in an intracranial melanoma xenograft and 19.85±3.63 μg/g in a subcutaneous melanoma xenograft. Intracranial melanoma showed more malignancy and shorter survival time than did subcutaneous melanoma when the same number of tumor cells were injected, and subcutaneous and intracranial amelanotic malignant melanoma tumors are both fitted for boron neutron capture therapy 1).

Case reports

2017

Primary Amelanotic CNS Melanoma: Case Report and Literature Review 2).

2015

Ma et al. report a case of intracranial amelanotic melanoma. Preoperative assessment revealed progressive right frontal mass. The patient underwent tumor resection. The pathologic analysis reported amelanotic melanoma of intermediate grade. The further examination of the whole brain and body was negative. The familial history was also negative. The patient recovered uneventfully and went on for radiotherapy and chemotherapy. After a follow-up period of 5 months, the patient was tumor-free.

This is the second report about primary CNS amelanotic melanoma. They summarized characteristics of the primary CNS melanocytic lesions and amelanotic melanoma with review of the literature and review of cases from the department 3).

2009

A 69-year-old man presented with trigeminal neuralgia. 4 years previously he underwent tumor removal with an initial diagnosis of amelanotic malignant cutaneous melanoma; 1 year later, because of tumor recurrence, the patient underwent neck dissection, chemotherapy and radiation. Magnet resonance imaging (MRI) disclosed an enhancement of the Gasserian ganglion and tumor extension along the mandibular and maxillar nerves of the intracranial part of the trigeminal nerve suggestive of tumor. The intraoperative macroscopic appearance of the tumor was compatible with a neurinoma. Histopathological studies proved the tumor to be a desmoplastic neurotropic melanoma (DNM) that was related to the previously treated malignant melanoma 4).

2008

Only 15 cases of intracranial amelanotic melanoma have been reported until 2008. A yellowish mass was observed in the frontal lobe. The content of the cyst consisted of old hematoma, xanthochromic fluid and necrotic tissue, was evacuated and the cyst wall was totally resected. No abnormal pigmentation was noted in the cyst wall and surrounding brain tissue. The imaging features of metastatic melanomas are distinctive due to the presence of melanin and the propensity for hemorrhage. Both hemorrhage and melanin can produce T1-weighted hyperintensity and T2-weighted signal intensity loss 5).

2006

A 63-year-old woman with diplopia and bilateral ptosis underwent brain MRI that showed a pituitary mass with signal characteristics suggestive of adenoma. Within one week she had developed nearly complete bilateral ophthalmoplegia. A repeat MRI showed extension of the mass into both cavernous sinuses. Hypophysectomy disclosed an amelanotic melanoma. Extensive search for a primary source was unsuccessful. Despite local radiation treatment, the tumor continued to grow and the patient became blind and died within several months of diagnosis. There are seven reported cases of melanoma arising primarily in the sella turcica. Two cases of metastatic melanoma to the cavernous sinuses have been reported. Amelanotic melanoma has not been reported as a cause of cavernous sinus syndrome 6).

1992

A thirty-four-year-old man was admitted to our hospital because of the disturbed visual acuity and pain on the eye movement of the right eye. He had prominent right eye and CT-scan and MRI of the brain disclosed a tumor which could be obviously distinguished from the extraocular muscles, optic nerve and the bulb of eye in the retrobulbar region. On operation we identified dark-red solid tumor which was 3.0cm in diameter, and diagnosed it malignant melanoma pathologically. Because postoperative study detected amelanotic melanoma in the white patch on the right upper extremity, this right orbital tumor was considered to be the metastasis of it from the right upper extremity. Metastatic malignant melanoma of the skin to the orbit is very rare, while most of the eye-associated malignant melanoma originates from uveal tract, special choroid, and conjunctiva. This case was the 26th case of these in the world and the first case in Japan, furthermore the 4th case in the world whose first symptoms were caused by the orbital metastasis 7).

1991

Primary intracranial amelanotic melanoma was verified at autopsy in a 38-year-old male. Correct diagnosis of amelanotic melanoma needs electron microscopy or immunohistochemistry, since Masson staining is negative due to the absence of melanin pigment. We adopted the following criteria for clinical use: macroscopically not dark and microscopically negative for Masson staining, but ultrastructurally various melanoma types present. Although the clinical profile of this case is consistent with melanotic melanoma, the more detailed features of primary intracranial amelanotic melanoma require future study 8).

1)

Sun T, Li Y, Wu T, Xie X, Chen G, Wei Y, Li B, Zhou Y, Du Z. Comparative analysis of pathology and boronophenylalanine uptake in experimental orthotopic and heterotopic amelanotic melanoma. Melanoma Res. 2014 Aug;24(4):315-21. doi: 10.1097/CMR.0000000000000086. PubMed PMID: 24915302.
2)

Mayer S, Mauer UM, Mathieu R, Hackenbroch C, Knupfer J, Schulz C. Primary Amelanotic CNS Melanoma: Case Report and Literature Review. J Neurol Surg A Cent Eur Neurosurg. 2017 Jul 27. doi: 10.1055/s-0037-1604326. [Epub ahead of print] PubMed PMID: 28750450.
3)

Ma J, Zhang Z, Li S, Chen X, Wang S. Intracranial amelanotic melanoma: a case report with literature review. World J Surg Oncol. 2015 May 12;13:182. doi: 10.1186/s12957-015-0600-z. Review. PubMed PMID: 25963017; PubMed Central PMCID: PMC4436165.
4)

Hashemi M, Stark A, Hugo H, Mehdorn M. Intracranial trigeminal nerve metastasis of a desmoplastic neurotropic melanoma: case report. Cent Eur Neurosurg. 2009 May;70(2):91-4. doi: 10.1055/s-0028-1082065. Epub 2009 May 25. PubMed PMID: 19711263.
5)

Cemil B, Emmez H, Oztanir N, Tokgoz N, Dogulu F. A cystic amelanotic melanoma metastasis to the brain: case report. Neurocirugia (Astur). 2008 Aug;19(4):365-7. PubMed PMID: 18726049.
6)

Jacob S, Pye E, Hbahbih M, Messios N, Rajabally YA. Rapidly progressive bilateral ophthalmoplegia and enlarging sellar mass caused by amelanotic melanoma. J Neuroophthalmol. 2006 Mar;26(1):49-50. PubMed PMID: 16518168.
7)

Toyoda H, Fukui K, Okabe H, Kitoh A, Iguchi I, Kanematsu I. [A case of malignant melanoma with orbital metastasis which caused the first symptoms]. No To Shinkei. 1992 Oct;44(10):929-33. Review. Japanese. PubMed PMID: 1285995.
8)

Seki Y, Ohara K, Aiba T, Unakami M, Hara M. Primary intracranial amelanotic melanoma–report of an autopsy case. Neurol Med Chir (Tokyo). 1991 Dec;31(12):773-6. PubMed PMID: 1726225.

Update: Chronic traumatic encephalopathy in American football players

There is tremendous media attention regarding chronic traumatic encephalopathy (CTE), primarily because of the deaths of high profile American football players who were found to have CTE upon neuropathology 1).

Physicians in clinical practice are likely to face an increasing number of retired football players seeking evaluation for chronic neurobehavioral symptoms. Guidelines for the evaluation and treatment of these patients are sparse. Clinical criteria for a diagnosis of CTE are under development. The contribution of CTE vs other neuropathologies to neurobehavioral symptoms in these players remains unclear.

Gardner et al. describe the experience in evaluating and treating a series of 14 self-referred symptomatic players. The aim is to raise awareness in the neurology community regarding the different clinical phenotypes, idiosyncratic but potentially treatable symptoms, and the spectrum of underlying neuropathologies in these players 2).

Altered Corpus Callosum White Matter Microstructure

Forty retired National Football League (NFL) players, ages 40-65, were matched by age and divided into two groups based on their age of first exposure (AFE) to tackle football: before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and seeded using deterministic tractography. Dependent measures were fractional anisotropy (FA), trace, axial diffusivity and radial diffusivity. Results showed that former NFL players in the AFE <12 group had significantly lower FA in anterior three CC regions and higher radial diffusivity in the most anterior CC region than those in the AFE ≥12 group. 3).

Prevention

Findings suggest that regulation of practice equipment could be a fair and effective way to substantially reduce subconcussive head impact in thousands of collegiate football players 4).

Case series

2017

Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history.

Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia.

Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre-high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia.

In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football 5).

1)

Riley DO, Robbins CA, Cantu RC, Stern RA. Chronic traumatic encephalopathy: Contributions from the Boston University Center for the Study of Traumatic Encephalopathy. Brain Inj. 2015;29(2):154-63. doi: 10.3109/02699052.2014.965215. PubMed PMID: 25587744.
2)

Gardner RC, Possin KL, Hess CP, Huang EJ, Grinberg LT, Nolan AL, Cohn-Sheehy BI, Ghosh PM, Lanata S, Merrilees J, Kramer JH, Berger MS, Miller BL, Yaffe K, Rabinovici GD. Evaluating and treating neurobehavioral symptoms in professional American football players: Lessons from a case series. Neurol Clin Pract. 2015 Aug;5(4):285-295. PubMed PMID: 26336629.
3)

Stamm JM, Koerte IK, Muehlmann M, Pasternak O, Bourlas AP, Baugh CM, Giwerc MY, Zhu A, Coleman MJ, Fritts NG, Martin B, Chaisson C, McClean MD, Lin AP, Cantu RC, Tripodis Y, Stern R, Shenton ME. Age at First Exposure to Football is Associated with Altered Corpus Callosum White Matter Microstructure in Former Professional Football Players. J Neurotrauma. 2015 Jul 22. [Epub ahead of print] PubMed PMID: 26200068.
4)

Reynolds BB, Patrie J, Henry EJ, Goodkin HP, Broshek DK, Wintermark M, Druzgal TJ. Practice type effects on head impact in collegiate football. J Neurosurg. 2015 Aug 4:1-10. [Epub ahead of print] PubMed PMID: 26238972.
5)

Mez J, Daneshvar DH, Kiernan PT, Abdolmohammadi B, Alvarez VE, Huber BR, Alosco ML, Solomon TM, Nowinski CJ, McHale L, Cormier KA, Kubilus CA, Martin BM, Murphy L, Baugh CM, Montenigro PH, Chaisson CE, Tripodis Y, Kowall NW, Weuve J, McClean MD, Cantu RC, Goldstein LE, Katz DI, Stern RA, Stein TD, McKee AC. Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football. JAMA. 2017 Jul 25;318(4):360-370. doi: 10.1001/jama.2017.8334. PubMed PMID: 28742910.

Update: Cervical arthroplasty

Cervical arthroplasty was developed with the goal of preserving mobility of the cervical segment in patients with cervical degenerative disc disease.

Cervical total disc replacement (TDR) has been shown in a number of prospective clinical studies to be a viable treatment alternative to anterior cervical discectomy and fusion (ACDF) for symptomatic cervical degenerative disc disease. In addition to preserving motion, evidence suggests that cervical TDR may result in a lower incidence of subsequent surgical intervention than treatment with fusion.

One reason for this trend is the observation that in clinical studies, patients with a history of cervical arthrodesis seem to have a higher incidence of adjacent segment degeneration 1) 2) 3).

Furthermore, in biomechanical investigations, most authors have reported an increase in the segmental range of motion (ROM) and the intradiscal pressure (IDP) in the levels proximal and distal to a simulated mono- or bisegmental arthrodesis 4) 5) 6) 7) 8) 9) 10) 11) 12) 13).

While anterior cervical discectomy and fusion (ACDF) has been the standard of care for 2-level disease, a randomized clinical trial (RCT) suggested similar outcomes.

There are also critical debates regarding the long-term effects of heterotopic ossification (HO) and the prevalence of adjacent-level degeneration.

Evidence

Several large-scale clinical trials demonstrate the efficacy of 1- and 2-level cervical disc arthroplasty (CDA) for degenerative disc disease (DDD) in the subaxial cervical spine, while other studies reveal that during physiological neck flexion, the C4-5 and C5-6 discs account for more motion than the C3-4 level, causing more degenerative disc disease (DDD).

The results of a observational study were in accordance with those of the published randomized controlled trials (RCTs), suggesting substantial pain reduction both after anterior cervical interbody fusion (AIF) and Cervical total disc replacement, with slightly greater benefit after arthroplasty. The analysis of atypical patients suggested that, in patients outside the spectrum of clinical trials, both surgical interventions appeared to work to a similar extent to that shown for the cohort in the matched study. Also, in the longer-term perspective, both therapies resulted in similar benefits to the patients 14).

The available evidence showed that most of the pre-selected factors had no effect on outcome after CTDR, and the range of motion (ROM) success rate, incidence of heterotopic ossification (HO) and radiographic adjacent segment degeneration (r-ASD)/adjacent segment disease (ASD), and surgery rate for ASD are acceptable. There is a lack of evidence for some factors 15).

With a significant exception of a Cochrane review, the methodological quality of systematic reviews evaluating the evidence of C-ADR versus ACDF has to be improved. 16).

Outcome

Cervical total disc replacement presented favorable functional outcomes, fewer adverse events, and fewer secondary surgical procedures. The efficacy and safety of cervical total disc replacement are superior to those of fusion. Longer-term, multicenter studies are required for a better evaluation of the long-term efficacy and safety of the two procedures.

Although cervical disc arthroplasty (CDA) at C3-4 was infrequent, the improved clinical outcomes of CDA were similar at C3-4 to that in the other subaxial levels of the cervical spine at the approximately 5-year follow-ups. In this Asian population, who had a propensity to have ossification of the posterior longitudinal ligament, there was more heterotopic ossification (HO) formation in patients who received CDA at the C3-4 level than in other subaxial levels of the cervical spine. While the type of artificial discs could have confounded the issue, future studies with more patients are required to corroborate the phenomenon 17).

Cost-effectiveness

A study is the first to report the comparative cost-effectiveness of cervical total disc replacement (cTDR) vs anterior cervical discectomy and fusion(ACDF) for 2-level degenerative disc disease at 5 years. Ament et al conclude that, because of the negative incremental cost-effective ratio (ICER), cTDR is the dominant modality 18)

Patients who underwent CTDR for single-level degenerative disease had lower readmission rates, lower reoperation rates, and reduced index and total costs than those treated with ACDF. Cervical disc arthroplasty (CDA) was effective in reducing the monthly cost of care compared with ACDF19).

Based on a modeling evaluation, CTDR was found to be more effective and less costly over a 7-year time horizon for patients with single-level symptomatic degenerative disc disease. These results are robust across a range of scenarios and perspectives and are intended to support value-based decision making 20).

The incremental cost-effectiveness ratio of CTDR compared with traditional ACDF is lower than the commonly accepted threshold of $50,000 per QALY. This remains true with varying input parameters in a robust sensitivity analysis, reaffirming the stability of the model and the sustainability of this intervention 21).

At the same time, while generating clinical results comparable to spinal fusion, TDR incurred significantly lower costs. Therefore, both from the medical and from the financial point of view, TDR is a viable choice in the treatment of DDP 22).

Results of the sensitivity analysis indicated that CDR must remain functional for at least 14 years to establish greater cost-effectiveness than ACDF. Since the current literature has yet to demonstrate with certainty the actual durability and long-term functionality of CDR, future long-term studies are required to validate the present analysis 23).


Although cervical total disc replacement (TDR) has shown equivalence or superiority to anterior cervical discectomy and fusion (ACDF), potential problems include nonphysiological motion (hypermobility), accelerated degeneration of the facet joints, particulate wear, and compromise of the mechanical integrity of the endplate during device fixation.

There is no definitive evidence that TDR has better intermediate-term results than anterior cervical discectomy and fusion (ACDF) 24).


3D motion analysis data comparing patients after ACDF and AD replacement in ten patients who underwent C5-6 ACDF and 7 who underwent C5-6 AD replacement were enrolled. Using biplanar fluoroscopy and a model-based track technique (accurate up to 0.6 mm and 0.6°), motion analysis of axial rotation and flexion-extension of the neck was performed. Three nonoperative segments (C3-4, C4-5, and C6-7) were assessed for both intervertebral rotation (coronal, sagittal, and axial planes) and facet shear (anteroposterior and mediolateral). Results There was no difference in total neck motion comparing ACDF and AD replacement for neck extension (43.3° ± 10.2° vs 44.3° ± 12.6°, p = 0.866) and rotation (36.0° ± 6.5° vs 38.2° ± 9.3°, p = 0.576). For extension, when measured as a percentage of total neck motion, there was a greater amount of rotation at the nonoperated segments in the ACDF group than in the AD group (p = 0.003). When comparing specific motion segments, greater normalized rotation was seen in the ACDF group at C3-4 (33.2% ± 4.9% vs 26.8% ± 6.6%, p = 0.036) and C6-7 (28.5% ± 6.7% vs 20.5% ± 5.5%, p = 0.009) but not at C4-5 (33.5% ± 6.4% vs 31.8% ± 4.0%, p = 0.562). For neck rotation, greater rotation was observed at the nonoperative segments in the ACDF group than in the AD group (p = 0.024), but the differences between individual segments did not reach significance (p ≥ 0.146). Increased mediolateral facet shear was seen on neck extension with ACDF versus AD replacement (p = 0.008). Comparing each segment, C3-4 (0.9 ± 0.5 mm vs 0.4 ± 0.1 mm, p = 0.039) and C4-5 (1.0 ± 0.4 mm vs 0.5 ± 0.2 mm, p = 0.022) showed increased shear while C6-7 (1.0 ± 0.4 mm vs 1.0 ± 0.5 mm, p = 0.767) did not.

This study illustrates increased motion at nonoperative segments in patients who have undergone ACDF compared with those who have undergone AD replacement. Further studies will be required to examine whether these changes contribute to adjacent-segment disease 25).

The data from a investigational device exemption (IDE) study through 48 months signify a number of clinically relevant benefits for total disc replacement (TDR) over anterior cervical discectomy and fusion (ACDF). Patients experienced improved clinical outcomes with TDR—including improvement in pain and function outcomes and superiority in overall primary endpoint success. Additionally, incidences of adjacent segment degeneration and subsequent surgeries were reduced with TDR. Perhaps future studies and also longer-term followup of this patient cohort may continue to establish 2-level cervical TDR as a superior surgical option for symptomatic degenerative disc disease 26).


Cervical artificial disc replacement (ADR) is indicated for the treatment of severe radiculopathy permitting neural decompression and maintenance of motion.

The clinical and radiographic outcomes in cervical ADR patients using the ProDisc-C device (DePuy Synthes, West Chester, PA, USA) with a 5-9 year follow-up were collected through a prospective registry, with retrospective analysis performed on 24 consecutive patients treated with cervical ADR by a single surgeon. All patients underwent single- or two-level ADR with the ProDisc-C device. Outcome measures included neck and arm pain (visual analogue scale), disability (neck disability index [NDI]), complications and secondary surgery rates. Flexion-extension cervical radiographs were performed to assess range of motion (ROM) of the device and adjacent segment disease (ASD). Average follow-up was 7.7 years. Neck and arm pain improved 60% and 79%, respectively, and NDI had an improvement of 58%. There were no episodes of device migration or subsidence. Mean ROM of the device was 6.4°. Heterotopic ossification was present in seven patients (37%). Radiographic ASD below the device developed in four patients (21%) (one single-level and three two-level ADR). No patient required secondary surgery (repeat operations at the index level or adjacent levels). Fourteen out of 19 patients (74%) were able to return to employment, with a median return to work time of 1.3 months. The ProDisc-C device for cervical ADR is a safe option for patients providing excellent clinical outcomes, satisfactory return to work rates and maintenance of segmental motion despite radiographic evidence of heterotopic ossification and ASD on long-term follow-up 27).

Types

Biomechanical analysis

Scarce references could be found and compared regarding the cervical ADR devices’ biomechanical differences that are consequently related to their different clinical results.

One fusion device (CJ cage system, WINNOVA) and three different cervical artificial discs (Prodisc-C Nova (DePuy Synthes), Discocerv (Scient’x/Alphatec), Baguera C (Spineart)) were inserted at C5-6 disc space inside the FE model and analyzed. Hybrid loading conditions, under bending moments of 1 Nm along flexion, extension, lateral bending and axial rotation with a compressive force of 50 N along the follower loading direction, were used in this study. Biomechanical behaviors such as segmental mobility, facet joint forces, and possible wear debris phenomenon inside the core were investigated.

The segmental motions as well as facet joint forces were exaggerated after ADR regardless of type of the devices. The Baguera C mimicked the intact cervical spine regarding the location of the center of rotation (COR) only during the flexion moment. It also showed a relatively wider distribution of the contact area and significantly lower contact pressure distribution on the core compared to the other two devices. A ‘lift off’ phenomenon was noted for other two devices according to the specific loading condition.

The mobile core artificial disc Baguera C can be considered biomechanically superior to other devices by demonstrating no ‘lift off’ phenomenon, and significantly lower contact pressure distribution on core 28).

Revision surgery and explantation

Between November 2008 and July 2016, 16 patients with prior implantation underwent removal of the Galileo-type disc prosthesis (Signus, Medizintechnik, Germany) due to a call back by industry. In 10 patients C-ADR was replaced with an alternative prosthesis, 6 patients received an ACDF. Duration of surgery, time to revision, surgical procedure, complication rate, neurological status, histological findings and outcome were examined in two institutions.

The C-ADR was successfully revised in all patients. Surgery was performed through the same anterior approach as the initial access. Duration of the procedure varied between 43 and 80min. Access-related complications included irritation of the recurrent nerve in one patient and mal-positioning of the C-ADR in another patient. Follow up revealed two patients with permanent mild/moderate neurologic deficits, NDI (neck disability index) ranged between 10 and 42%.

Anterior exposure of the cervical spine for explantation and revision of C-ADR performed through the initial approach has an overall complication rate of 18.75%. Replacements of the Galileo-type disc prosthesis with an alternative prosthesis or conversion to ACDF are both suitable surgical options without significant difference in outcome 29).

Case series

2017

As part of an FDA IDE trial, a single center collected prospective outcomes data on 47 patients randomized in a 1:1 ratio to ACDF or arthroplasty.

Success of both surgical interventions remained high at the 10-year interval. Both arthrodesis and arthroplasty demonstrated statistically significant improvements in neck disability index, visual analog scale neck and arm pain scores at all intervals including 7- and 10-year periods. Arthroplasty demonstrated an advantage in comparison to arthrodesis as measured by final 10-year NDI score (8 vs. 16, P = 0.0485). Patients requiring reoperation were higher in number in the arthrodesis cohort (32%) in comparison with arthroplasty (9%) (P = 0.055).

At 7 and 10 years, cervical arthroplasty compares favorably with ACDF as defined by standard outcomes scores in a highly selected population with radiculopathy 30).

2016

A total of 200 subjects underwent single-level activC® (Aesculap AG) implantation between C-3 and C-7 for the treatment of symptomatic degenerative disc disease. Clinical and radiographic assessments were performed preoperatively, intraoperatively, at discharge, and again at 6 weeks, 6 months, 1 year, 2 years, and 4 years. Radiographic evaluations were done by an independent core laboratory using a specific software for quantitative motion analysis.

Neck Disability Index (NDI) and visual analog scale (VAS) score for neck and arm pain decreased significantly from baseline to the 4-year follow-up. The mean improvement for NDI was 20, for VAS severity and frequency of neck pain 26.4 and 28, and for VAS severity and frequency of arm pain 30.7 and 35.1, respectively. The neurological situation improved for the majority of patients (86.4%); 76.1% of cases were asymptomatic. Subsequent surgical interventions were reported in 7% of the cases, including device removals in 3%. In 2.5% a subsidence greater than 3 mm was recorded; 1 of these cases also had a migration greater than 3 mm. No device displacement, expulsion, disassembly, loose or fractured device, osteolysis, or facet joint degeneration at the index level was observed. Segmental lordotic alignment changed from -2.4° preoperatively to -6.2° at 4 years, and postoperative height was maintained during the follow-up. Advanced HO (Grade III and IV) was present in 27.1% of the cases; 82.4% showed segmental mobility. A progression of radiographic adjacent-segment degeneration occurred in 28.2%, but only 4.5% required surgical treatment.

The activ C is a safe and effective device for cervical disc replacement confirming the encouraging results after cTDR. Clinical trial registration no.: NCT02492724 ( clinicaltrials.gov ) 31)


A total of 225 patients received the Mobi-C cervical total disc replacement device and 105 patients received ACDF. The Mobi-C and ACDF follow-up rates were 90.7% and 86.7%, respectively (p = 0.39), at 60 months. There was significant improvement in all outcome scores relative to baseline at all time points. The Mobi-C patients had significantly more improvement than ACDF patients in terms of Neck Disability Index score, SF-12 Physical Component Summary, and overall satisfaction with treatment at 60 months. The reoperation rate was significantly lower with Mobi-C (4%) versus ACDF (16%). There were no significant differences in the adverse event rate between groups.

Both cervical total disc replacement and ACDF significantly improved general and disease-specific measures compared with baseline. However, there was significantly greater improvement in general and disease-specific outcome measures and a lower rate of reoperation in the 2-level disc replacement patients versus ACDF control patients. Clinical trial registration no. NCT00389597 ( clinicaltrials.gov ) 32).


Twenty patients (12 females, 8 males; median age 45.6 ± 6.9 years) treated by ACDA (BryanDisc®, Medtronic, Minneapolis, USA) underwent plain functional radiography and kinematic MRI of the cervical spine at 3T before and 6 and 24 months after surgery.

A sagittal T2-weighted (T2w) 2D turbo spin echo (TSE) sequence and a 3D T2w dataset with secondary axial reconstruction were acquired. Signal intensity of all nonoperated discs was measured in regions of interest (ROI). Disc heights adjacent to the operated segment were measured. Range of motion (ROM) was evaluated and compared to plain functional radiographs. Clinical outcome was evaluated using the visual analog scale (VAS) for head, neck and radicular pain, and the neck disability index (NDI).

Mean ROM of the cervical spine on functional plain radiographs was 21.25 ± 8.19, 22.29 ± 4.82 and 26.0 ± 6.9 degrees preoperatively and at 6-month and 24-month follow-up, respectively. Mean ROM at MRI was 27.1 ± 6.78, 29.45 ± 9.51 and 31.95 ± 9.58 degrees, respectively. There was good correlation between both techniques. Follow-up examinations demonstrated no signs of progressive degenerative disc disease of adjacent levels. All patients had clinical improvement up to 24 months after surgery.

After ACDA, kinematic MRI allows evaluation of the ROM with excellent correlation to plain functional radiographs. Mid-term follow-up after ACDA is without evidence of progressive DDD of adjacent segments 33).


A prospective, multicenter, randomized, unblinded clinical trial. Patients with symptomatic degenerative disc disease were enrolled to receive 1- or 2-level treatment with either TDR as the investigational device or ACDF as the control treatment. There were 260 patients in the 1-level study (179 TDR and 81 ACDF patients) and 339 patients in the 2-level study (234 TDR and 105 ACDF patients). RESULTS At 5 years, the occurrence of subsequent surgical intervention was significantly higher among ACDF patients for 1-level (TDR, 4.5% [8/179]; ACDF, 17.3% [14/81]; p = 0.0012) and 2-level (TDR, 7.3% [17/234]; ACDF, 21.0% [22/105], p = 0.0007) treatment. The TDR group demonstrated significantly fewer index- and adjacent-level subsequent surgeries in both the 1- and 2-level cohorts.

Five-year results showed treatment with cervical TDR to result in a significantly lower rate of subsequent surgical intervention than treatment with ACDF for both 1 and 2 levels of treatment. Clinical trial registration no.: NCT00389597 ( clinicaltrials.gov ) 34).

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Update: Awake surgery

An awake craniotomy is a safe neurosurgical procedure that minimizes the risk of brain injury. During the course of this surgery, the patient is asked to perform motor or cognitive tasks, but some patients exhibit severe sleepiness.

For neurosurgery with an awake craniotomy, the critical issue is to set aside enough time to identify eloquentcortices by electrocortical stimulation (ECS). High gamma activity (HGA) ranging between 80 and 120 Hz on electrocorticogram (ECoG) is assumed to reflect localized cortical processing.

Indications

Gross total removal of glioma is limited by proximity to eloquent brain. Awake surgery allows for intraoperative monitoring to safely identify eloquent regions.


For a long time, the right hemisphere (RH) was considered as “non-dominant”, especially in right-handers. In neurosurgical practice, this dogma resulted in the selection of awake craniotomy with language mapping only for lesions of the left dominant hemisphere. Conversely, surgery under general anesthesia (possibly with motor mapping) was usually proposed for right lesions. However, when objective neuropsychological tests were performed, they frequently revealed cognitive and behavioral deficits following brain surgery, even in the RH. Therefore, to preserve an optimal quality of life, especially in patients with a long survival expectancy (as in low-grade gliomas), awake surgery with cortical and axonal electrostimulation mapping has recently been proposed for right tumors resection. Here, we review new insights gained from intraoperative stimulation into the pivotal role of the RH in movement execution and control, visual processes and spatial cognition, language and non-verbal semantic processing, executive functions (e.g. attention), and social cognition (mentalizing and emotion recognition). Such original findings, that break with the myth of a “non-dominant” RH, may have important implications in cognitive neurosciences, by improving our knowledge of the functional connectivity of the RH, as well as for the clinical management of patients with a right lesion. Indeed, in brain surgery, awake mapping should be considered more systematically in the RH. Moreover, neuropsychological examination must be achieved in a more systematic manner before and after surgery within the RH, to optimize the care by predicting the likelihood of functional recovery and by elaborating specific programs of rehabilitation 1).

Operations in eloquent areas

Awake craniotomy was introduced for surgical treatment of epilepsy, and has subsequently been used in patients with supratentorial tumors, intracranial arteriovenous malformationdeep brain stimulation, and mycotic aneurysms near critical regions of brain.

Patients are selected for awake craniotomy when the planned procedure involves eloquent areas of the brain, necessitating an awake, cooperative patient capable of undergoing neurocognitive testing, especially speech area, (Broca’s areaWernicke’s area) near motor stripthalamus, removal of brainstem tumors, some seizure surgery.

The critical issue is to set aside enough time to identify eloquent cortices by electrocortical stimulation (ECS). High gamma activity (HGA) ranging between 80 and 120 Hz on electrocorticogram (ECoG) is assumed to reflect localized cortical processing. In this report, we used realtime HGA mapping and functional magnetic resonance imaging (fMRI) for rapid and reliable identification of motor and language functions. Three patients with intra-axial tumors in their dominant hemisphere underwent preoperative fMRI and lesion resection with an awake craniotomy. All patients showed significant fMRI activation evoked by motor and language tasks. After the craniotomy, we recorded ECoG activity by placing subdural grids directly on the exposed brain surface. Each patient performed motor and language tasks and demonstrated realtime HGA dynamics in hand motor areas and parts of the inferior frontal gyrus. Sensitivity and specificity of HGA mapping were 100% compared to ECS mapping in the frontal lobe, which suggested HGA mapping precisely indicated eloquent cortices. The investigation times of HGA mapping was significantly shorter than that of ECS mapping. Specificities of the motor and language-fMRI, however, did not reach 85%. The results of HGA mapping was mostly consistent with those of ECS mapping, although fMRI tended to overestimate functional areas. This novel technique enables rapid and accurate functional mapping 2).

Awake craniotomy for glioma

Craniotomies for glioma resection under conscious sedation (CS) have been well-documented in the literature for gliomas that are in or adjacent to eloquent areas 3) 4) 5) 6) 7).

Awake surgery for glioma aims to maximize resection to optimize prognosis while minimizing the risk of postoperative deficits.

The oncological and functional results of awake glioma surgery during the learning curve are comparable to results from established centers. The use and utility of resection probability maps are well demonstrated. The return to work level is high 8).

AC with the input of the speech and language therapist (SLT) and an experienced neuro-physiotherapist (NP) is a key component in ensuring optimal functional outcomes for patients with gliomas in eloquently located areas 9).

5 aminolevulinic acid guidance during awake craniotomy

Corns et al. describe the case of a patient with recurrent left frontal GBM encroaching on Broca’s area (eloquent brain). Gross total resection of the tumour was achieved by combining two techniques, awake resection to prevent damage to eloquent brain and 5-ALA fluorescence guidance to maximise the extent of tumour resection.This technique led to gross total resection of all T1-enhancing tumour with the avoidance of neurological deficit. The authors recommend this technique in patients when awake surgery can be tolerated and gross total resection is the aim of surgery 10)

Contraindications

Uncooperative (very young or too old patient).

Confusion.

Speech deficit

Language barrier

Brain mapping

Electrocortical stimulation (ECS) is the gold standard for functional brain mapping during an awake craniotomy.

Awake craniotomy could be challenging because of unsecured airway with risks of vomitting, epileptic attacks or unstable level of consciousness. It is considered that the patient monitoring becomes more difficult when iMRI is performed because the patient’s face cannot be obsereved directly. We should remember that conscious level as well as respiration pattern may change during operation 11).

Awake craniotomy can be safely performed in a high-field (1.5 T) iMRI suite to maximize tumor resection in eloquent brain areas with an acceptable morbidity profile at 1 month 12).

The routine use of fMRI was not useful in identifying language sites as performed and, more importantly, practiced tasks failed to prevent neurological deficits following awake craniotomy procedures 13).

Management of anesthesia

The importance of minimizing pain and preparing patients thoroughly to reduce anxiety and maximize cooperation. Awake surgery is an excellent treatment modality for brain tumors with very positive perception by patients 14).

Different anesthetic combinations, including neurolept, propofol with or without opioid infusions, and asleep-awake-asleep techniques, have been reported for awake craniotomy. In all these techniques, respiratory depression has been reported as a complication.

see dexmedetomidine

Different protocols exist for anesthetic care during awake craniotomy based on monitored anesthesia care (MAC) or general anesthesia (asleep-awake-asleep technique). Nevertheless the administration of anesthetics, expectedly, is not without drawbacks, side effects and risks. A new approach for awake craniotomies emphasizes the need of adequate communication with patients 15).

Scalp block

see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236942/#ref11

Awake surgery with intraoperative brain mapping is highly recommended for patients with diffuse low grade gliomas in language areas, to maximise the extent of resection while preserving the integrity of functional networks and thus quality of life.

The picture naming test DO 80 is the gold standard for language assessment before, during, and after surgery.

Cognitive functioning is correlated with quality of life, itself linked with return to work.

The objective was to evaluate the significance of measuring naming speed, and its correlation with the return to professional activities. Two complementary studies are reported. In the first retrospective study, eleven patients were examined post-operatively. Five patients were selected because they were not able to resume their professional activities (“no return group 1”). They were compared with a control group of six patients who are working normally after surgery (“return group 1”). The eleven patients performed a global language and neuropsychological assessment, with a post-operative median follow-up of 35 months. In a subsequent prospective study, twelve patients were examined pre-operatively and post-operatively. Six patients who were not able to return to work (“no return group 2”) were compared with a control group of six patients who were working normally after the surgery (“return group 2”). The twelve patients performed a pre and post-operative language assessment, with a median follow-up of 9 months. Our results show, for the first time, that naming speed is significantly correlated with a major criterion of quality of life: the return to professional activities. There were no differences between the two groups regarding other measures of cognition. Assessing naming times, and not only naming accuracy, is essential in the management of low-grade glioma patients, before, during, and after surgery, to preserve their quality of life by resuming their previous professional activity. Our results have fundamental implications concerning the comprehension of language processing and its relationship with cognitive functioning 16).

Cost effectiveness

Retrospective analysis of a cohort of 17 patients with perirolandic gliomas who underwent an AC with DCS were case-control matched with 23 patients with perirolandic gliomas who underwent surgery under GA with neuromonitoring (ie, motor-evoked potentials, somatosensory-evoked potentials, phase reversal). Inpatient costs, quality-adjusted life years (QALY), extent of resection, and neurological outcome were compared between the groups.

Total inpatient expense per patient was ${\$}$ 34 804 in the AC group and ${\$}$ 46 798 in the GA group ( P = .046). QALY score for the AC group was 0.97 and 0.47 for the GA group ( P = .041). The incremental cost per QALY for the AC group was ${\$}$ 82 720 less than the GA group. Postoperative Karnofsky performance status was 91.8 in the AC group and 81.3 in the GA group (P = .047). Length of hospitalization was 4.12 days in the AC group and 7.61 days in the GA group ( P = .049).

The total inpatient costs for awake craniotomies were lower than surgery under GA. This study suggests better cost effectiveness and neurological outcome with awake craniotomies for perirolandic gliomas 17).

Case series

2017

Motomura et al. retrospectively reviewed the records of 33 consecutive patients with glial tumors in the eloquent brain areas who underwent awake surgery using iMRI. Volumetric analysis of MRI studies was performed. The pre-, intra-, and postoperative tumor volumes were measured in all cases using MRI studies obtained before, during, and after tumor resection. RESULTS Intraoperative MRI was performed to check for the presence of residual tumor during awake surgery in a total of 25 patients. Initial iMRI confirmed no further tumor resection in 9 patients (36%) because all observable tumors had already been removed. In contrast, intraoperative confirmation of residual tumor during awake surgery led to further tumor resection in 16 cases (64%) and eventually an EOR of more than 90% in 8 of 16 cases (50%). Furthermore, EOR benefiting from iMRI by more than 15% was found in 7 of 16 cases (43.8%). Interestingly, the increase in EOR as a result of iMRI for tumors associated mainly with the insular lobe was significantly greater, at 15.1%, than it was for the other tumors, which was 8.0% (p = 0.001).

This study revealed that combining awake surgery with iMRI was associated with a favorable surgical outcome for intrinsic brain tumors associated with eloquent areas. In particular, these benefits were noted for patients with tumors with complex anatomy, such as those associated with the insular lobe 18).

2016

Four illustrative cases demonstrate the efficacy of using a tablet computer platform for advanced language mapping testing with sophisticated language paradigms, and the spatial agreement between intraoperative mapping and preoperative fMRI results. The testing platform substantially improved the ability of the surgeon to detect and characterize language deficits. Use of a written word generation task to assess language production helped confirm areas of speech apraxia and speech arrest that were inadequately characterized or missed with the use of traditional paradigms, respectively. Preoperative fMRI of the analogous writing task was also assistive, displaying excellent spatial agreement with intraoperative mapping in all 4 cases. Sole use of traditional testing paradigms can be limiting during awake craniotomy procedures. Comprehensive assessment of language function will require additional use of more sophisticated and ecologically valid testing paradigms. The platform presented here provides a means to do so 19).

2015

Thirty-seven patients with brain tumor who underwent awake craniotomy were included in this study. Prior to craniotomy, the patient evaluated cognitive status, and during the surgery, each patient’s performance and attitude toward cognitive tasks were recorded by neuropsychologists.

The present findings showed that the construction and calculation abilities of the patients were moderately correlated with their sleepiness.

These results indicate that the preoperative cognitive functioning of patients was related to their sleepiness during the awake craniotomy procedure and that the patients who exhibited sleepiness during an awake craniotomy had previously experienced reduced functioning in the parietal lobe 20).

2009

From 1998 to 2007, 79 consecutive fully awake craniotomy (FAC)s for resection primary supratentorial brain tumors (PSBT) near or in eloquent brain areas (EBA), performed by a single surgeon, were prospectively followed. Two groups were defined based on time period and surgical team: group A operated on from March 1998 to July 2004 without a multidisciplinary team and group B operated on from August 2004 to October 2007 in a multidisciplinary setting. For both time periods, two groups were defined: group I had no previous history of craniotomy, while group II had undergone a previous craniotomy for a PSBT. Forty-six patients were operated on in group A, 46 in group B, 49 in group I and 30 in group II. Psychological assessment and selection were obligatory. The preferred anesthetic procedure was an intravenous high-dose opioid infusion (Fentanil 50 microg, bolus infusion until a minimum dose of 10 microg/kg). Generous scalp and periosteous infiltrations were performed. Functional cortical mapping was performed in every case. Continuous somato-sensory evoked potentials (SSEPs) and phase reversal localization were available in 48 cases. Standard microsurgical techniques were performed and monitored by continuous clinical evaluation.

Clinical data showed differences in time since clinical onset (p < 0.001), slowness of thought (p = 0.02) and memory deficits (p < 0.001) between study periods and also time since recent seizure onset for groups I and II (p = 0.001). Mean tumor volume was 51.2 +/- 48.7 cm3 and was not different among the four groups. The mean extent of tumor reduction was 90.0 +/- 12.7% and was similar for the whole series. A trend toward a larger incidence of glioblastoma multiforme occurred in group B (p = 0.05) and I (p = 0.04). Recovery of previous motor deficits was observed in 75.0% of patients, while motor worsening in 8.9% of cases. Recovery of semantic language deficits, control of refractory seizures and motor worsening were statistically more frequent in group B (p = 0.01). Satisfaction with the procedure was reported by 89.9% of patients, which was similar for all groups. Clinical complications were minimal, and surgical mortality was 1.3%.

These data suggest that FAC is safe and effective for the resection of PSBT in EBA as the main technique, and in a multidisciplinary context is associated with greater clinical and physiological monitoring. The previous history of craniotomy for PSBT did not seem to influence the outcome21).

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