Awake Intraoperative Language Mapping and Chinese Probabilistic Map Construction

Glioma Clinical Trial

Official title:

Prospective Study of Awake Intraoperative Language Mapping and Construction of Chinese Probabilistic Map Based on Direct Electrical Stimulation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03641391
• Other study ID #: KY2012-009
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2018
• Est. completion date: December 1, 2023

Study information

• Verified date: August 2018
• Source: Huashan Hospital
• Contact: Jinsong Wu, MD
• Phone: 86-021-52887200
• Email: wjsongc[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims at constructing a Chinese language probabilistic map by awake intraoperative direct electrical stimulation (DES) language mapping. At the same time, the standardization and optimization of awake intraoperative DES parameters will be explored, factors affecting postoperative function morbidity and survival will also be analyzed.

Description:

The study aims at constructing a Chinese language probabilistic map by awake intraoperative direct electrical stimulation (DES) language mapping.

The "maximal safe resection" of brain tumor adjacent to language cortex requires precise real-time localization of the intraoperative language cortex.

Awake craniotomy combined with DES to localize language cortex has been carried out for several decades. However, there is yet no unified standard on the specification of its technical parameters. Besides, language probabilistic maps based on DES have been reported by several teams around the world. However these studies were based on the Indo-European language speakers alone. There was one paper published in 2015 by the investigators' group using DES for the Chinese probabilistic map, but it is also a single center study, and the sample size is relatively small.

Awake craniotomy and intraoperative DES for language cortex localization will be used to construct a Chinese probabilistic map in this study. Several common tasks for language mapping (i.e., number counting, picture naming, word reading) will be applied in Chinese speakers. The positive language sites including speech arrest, anomia, alexia, anarthria, dysarthria, semantic paraphasia and phonological paraphasia, spatial negativity and other higher order cognitive function will be identified in individual patients and normalized to the standard brain atlas. The corresponding probabilistic maps will be integrated and generated.

At the same time, the standardization and optimization of awake intraoperative DES parameters will be explored, factors affecting postoperative function morbidity and survival will also be analyzed.

Through this study, the investigators will further popularize individualized awake surgery of glioma in language cortex, improve the extent of tumor resection, protect postoperative language function and improve postoperative quality of life. By constructing this standardized Chinese probabilistic map, the investigators will provide more direct evidence for brain language research.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: December 1, 2023
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Individuals aged 14-70 years with highly suspected (as assessed by study surgeon), newly diagnosed, untreated malignant glioma;

2. Individuals with gliomas with bodies involving in dominate side language area(see appendix 1);

3. Individuals with the preoperative assessment that radiological radically should be achieved;

4. Individuals who are cooperative and well tolerated with awake craniotomy;

5. Individuals presents with good communicate and explanation preoperatively;

6. All participants gave written informed consent.

Appendix 1. Tumor location in eloquent areas: located in or close to areas of the dominant-hemisphere that associated with motor or language functions, including:

1. Frontal lobe, which divided into inferior frontal gyrus (BA44-Pars opercularis, BA45-Pars triangularis/Broca's area), middle frontal gyrus (BA9, BA46), superior frontal gyrus (BA4, BA6, BA8), primary motor cortex (BA4), premotor cortex (BA6), and supplementary motor area (BA6);

2. Parietal lobe, which divided into inferior parietal lobule (BA40- supramarginal gyrus, BA39-angular gyrus), parietal operculum (BA43), and primary somatosensory cortex (BA1, BA2, BA3);

3. Temporal lobe, which divided into transverse temporal gyrus (BA41, BA42), superior temporal gyrus (BA38, BA22/Wernicke's area), middle temporal gyrus (BA21);

4. Insular lobe.

Exclusion Criteria:

1. Individuals with age < 14 years or > 70 years;

2. Individuals presents with impaired cognitive function or unstable mental status;

3. Individuals has higher intracranial pressure, sleep apnea syndrome, difficult airway or morbid obesity, claustrophobia, uncontrolled coughing, uncontrolled seizures or inability to stay still etc.;

4. Recurrent gliomas after surgery (except needle biopsy);

5. Primary gliomas with history of radiotherapy or chemotherapy;

6. Renal insufficiency or hepatic insufficiency;

7. History of malignant tumors at any body site;

8. Tumors of the midline, basal ganglia, cerebellum, or brain stem;

9. Inability or unwilling to give informed consent.

Related Conditions & MeSH terms

• Glioma

Intervention

Procedure:
• Intraoperative direct cortical electrical stimulation
Intraoperative direct electrical stimulation on language or language-associate cortex, was performed using a 5-mm wide bipolar electrode with a pulse frequency of 60 Hz and an amplitude of 1.5 to 6 milliamperage. The somatosensory evoked potential was recorded with a 6-contact subdural strip electrode. If after-discharge activity indicated that the stimulation current was too high, the current amplitude was decreased by 0.5 to 1 milliamperage. The participants would be undergone awake anesthesia and asked to perform language tasks during the stimulation.
• Intraoperative direct subcortical electrical stimulation
Intraoperative direct electrical stimulation on language or language-associate subcortical pathways, was performed using a biphasic square-wave pulse delivered at 60 Hz with a current amplitude ranging from 1.5 to 10 milliamperage. The somatosensory evoked potential was recorded with a 6-contact subdural strip electrode. If after-discharge activity indicated that the stimulation current was too high, the current amplitude was decreased by 0.5 to 1 milliamperage. The participants would be undergone awake anesthesia and asked to perform language tasks during the stimulation.

Locations

Country	Name	City	State
China	Huashan Hospital Affiliated to Fudan University	Shanghai	Shanghai
China	Huashan Hospital North, Fudan University	Shanghai	Shanghai
China	Zhongshan Hospital Affiliated to Fudan University	Shanghai	Shanghai

Sponsors (3)

Lead Sponsor	Collaborator
Huashan Hospital	Huashan Hospital North, Fudan University, Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (10)

Breshears JD, Molinaro AM, Chang EF. A probabilistic map of the human ventral sensorimotor cortex using electrical stimulation. J Neurosurg. 2015 Aug;123(2):340-9. doi: 10.3171/2014.11.JNS14889. Epub 2015 May 15. — View Citation

Chang EF, Breshears JD, Raygor KP, Lau D, Molinaro AM, Berger MS. Stereotactic probability and variability of speech arrest and anomia sites during stimulation mapping of the language dominant hemisphere. J Neurosurg. 2017 Jan;126(1):114-121. doi: 10.3171/2015.10.JNS151087. Epub 2016 Feb 19. — View Citation

Duffau H. Stimulation mapping of white matter tracts to study brain functional connectivity. Nat Rev Neurol. 2015 May;11(5):255-65. doi: 10.1038/nrneurol.2015.51. Epub 2015 Apr 7. Review. — View Citation

Lu J, Wu J, Yao C, Zhuang D, Qiu T, Hu X, Zhang J, Gong X, Liang W, Mao Y, Zhou L. Awake language mapping and 3-Tesla intraoperative MRI-guided volumetric resection for gliomas in language areas. J Clin Neurosci. 2013 Sep;20(9):1280-7. doi: 10.1016/j.jocn.2012.10.042. Epub 2013 Jul 10. — View Citation

Nakai Y, Jeong JW, Brown EC, Rothermel R, Kojima K, Kambara T, Shah A, Mittal S, Sood S, Asano E. Three- and four-dimensional mapping of speech and language in patients with epilepsy. Brain. 2017 May 1;140(5):1351-1370. doi: 10.1093/brain/awx051. — View Citation

Ritaccio AL, Brunner P, Schalk G. Electrical Stimulation Mapping of the Brain: Basic Principles and Emerging Alternatives. J Clin Neurophysiol. 2018 Mar;35(2):86-97. doi: 10.1097/WNP.0000000000000440. — View Citation

Sanai N, Mirzadeh Z, Berger MS. Functional outcome after language mapping for glioma resection. N Engl J Med. 2008 Jan 3;358(1):18-27. doi: 10.1056/NEJMoa067819. — View Citation

Tate MC, Herbet G, Moritz-Gasser S, Tate JE, Duffau H. Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited. Brain. 2014 Oct;137(Pt 10):2773-82. doi: 10.1093/brain/awu168. Epub 2014 Jun 25. — View Citation

Wu J, Lu J, Zhang H, Zhang J, Mao Y, Zhou L. Probabilistic map of language regions: challenge and implication. Brain. 2015 Mar;138(Pt 3):e337. doi: 10.1093/brain/awu247. Epub 2014 Sep 4. — View Citation

Wu J, Lu J, Zhang H, Zhang J, Yao C, Zhuang D, Qiu T, Guo Q, Hu X, Mao Y, Zhou L. Direct evidence from intraoperative electrocortical stimulation indicates shared and distinct speech production center between Chinese and English languages. Hum Brain Mapp. 2015 Dec;36(12):4972-85. doi: 10.1002/hbm.22991. Epub 2015 Sep 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate of postoperative language deficits	Language deficits were considered when the participant presents with aphasia or severe dysphasia measured by standardized Aphasia Battery of Chinese (ABC, a Chinese version of Western Aphasia Battery) having the Aphasia Quotient (AQ) less than 50 (where lower values represent a worse outcome).	The first month and the third month after surgery
Secondary	Location of positive sites in cortical mapping	Positive stimulation of the language area was assumed when the participant exhibited counting interruption, errors during object naming, language confusion or other language problems induced by DES.; Positive stimulation of the motion area was assumed when movements of the contralateral limb, face, lip or tongue were induced by DES, with the concurrent recording of an electromyogram.; Positive stimulation affecting the sensation area was assumed when an abnormal feeling was induced by DES in the contralateral limb, face, lip or tongue.; The locations of positive sites will be recorded by neuro-navigation system.	During surgery
Secondary	Incidence rate of intraoperative epilepsy induced by direct cortical stimulation	A strip electrode would be placed tangentially over the central sulcus to monitor cortical seizure activity or after-discharge during intraoperative DCS. And the participant would be closely observed for involuntarily shaking or twitching. Any shaking, twitching or after-discharge during monitor would considered as epileptic event. All epileptic events will be recorded and DES will be terminated for the participant.	During surgery
Secondary	Extent of resection	Extent of resection (EOR) based on early postoperative MRI obtained within 72h after surgery. Gross total resection (GTR) was defined as the complete disappearance of all enhancing lesions (T1WI) for HGG and the complete disappearance of all nonenhancing (T2WI FLAIR) lesions for LGG. The EOR were quantitatively volumetric analyses for all gliomas and gliomas grouped according to eloquent areas and non-eloquent areas, and stratified as: GTR, 100% resection; subtotal resection = 90% resection, partial resection = 70% resection, biopsy, resection =98% for overall survival advantage (HGG) and resection =90% for overall survival advantage (LGG).	Within 72h after surgery