Bilateral and asymmetrical localization of language function identified by the superselective infusion of propofol in an epilepsy patient with a mild malformation of cortical development: illustrative case

Mayuko Otomo Departments of Neurosurgery,

Search for other papers by Mayuko Otomo in
Current site
jns
Google Scholar
PubMed
Close
 MD
,
Shin-ichiro Osawa Departments of Neurosurgery,

Search for other papers by Shin-ichiro Osawa in
Current site
jns
Google Scholar
PubMed
Close
 MD, PhD
,
Kyoko Suzuki Behavioral Neurology and Cognitive Neuroscience

Search for other papers by Kyoko Suzuki in
Current site
jns
Google Scholar
PubMed
Close
 MD, PhD
,
Kazuo Kakinuma Behavioral Neurology and Cognitive Neuroscience

Search for other papers by Kazuo Kakinuma in
Current site
jns
Google Scholar
PubMed
Close
 MD, PhD
,
Kazushi Ukishiro Epileptology, and

Search for other papers by Kazushi Ukishiro in
Current site
jns
Google Scholar
PubMed
Close
 MD, PhD
,
Hiroyoshi Suzuki Department of Pathology, Sendai Medical Center, Sendai, Miyagi, Japan

Search for other papers by Hiroyoshi Suzuki in
Current site
jns
Google Scholar
PubMed
Close
 MD, PhD
,
Kuniyasu Niizuma Departments of Neurosurgery,
Department of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Miyagi, Japan; and
Neurosurgical Engineering and Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Search for other papers by Kuniyasu Niizuma in
Current site
jns
Google Scholar
PubMed
Close
 MD, PhD
,
Norio Narita Department of Neurosurgery, Kesennuma City Hospital, Kesennuma, Miyagi, Japan

Search for other papers by Norio Narita in
Current site
jns
Google Scholar
PubMed
Close
 MD, PhD
,
Nobukazu Nakasato Epileptology, and

Search for other papers by Nobukazu Nakasato in
Current site
jns
Google Scholar
PubMed
Close
 MD, PhD
, and
Teiji Tominaga Departments of Neurosurgery,

Search for other papers by Teiji Tominaga in
Current site
jns
Google Scholar
PubMed
Close
 MD, PhD
Open access

BACKGROUND

Atypical localization of language function can result in unexpected postsurgical deficits after cortical resection, but it is difficult to predict the risk in the presurgical evaluation. The authors experienced a rare case of the bilateral and independent existence of different components of language function identified by segmented evaluation of anatomical anterior and posterior language areas using the superselective infusion of propofol.

OBSERVATIONS

A 32-year-old right-handed female presented with drug-resistant epilepsy. Comprehensive epilepsy evaluation suggested that the epileptic foci involved the whole left frontal lobe but provided less evidence of structural abnormality. To estimate the extent of functional deterioration likely to be caused by an extended left frontal lobectomy, the authors evaluated segmented cortical function in the ipsi- and contralateral hemispheres by the superselective infusion of propofol into the branches of the intracranial artery. The results revealed bilateral and asymmetrical localization of language function because the patient presented with different components of aphasia in each hemisphere. Based on the authors’ assessment of her functional tolerance, an extended left frontal lobectomy was performed and resulted in neurological deficits within the anticipated range.

LESSONS

An accurate understanding of the correlations between vascular and functional anatomy and the highly specific evaluation of language function provides more advanced presurgical assessment, allowing more tailored planning of cortical resection.

ABBREVIATIONS

EEG = electroencepholography; ECS = electrical cortical stimulation; FDG-PET = fluorodeoxyglucose positron emission tomography; fMRI = functional magnetic resonance imaging; ICA = internal carotid artery; IQ = intelligence quotient; LT-VEEG = long-term video electroencephalography; MCA = middle cerebral artery; MOGHE = malformation of cortical development with oligodendroglial hyperplasia and epilepsy; MRI = magnetic resonance imaging; OLC = oligodendrocyte-like cell; ssWada = superselective Wada; WAB = Western Aphasia Battery

BACKGROUND

Atypical localization of language function can result in unexpected postsurgical deficits after cortical resection, but it is difficult to predict the risk in the presurgical evaluation. The authors experienced a rare case of the bilateral and independent existence of different components of language function identified by segmented evaluation of anatomical anterior and posterior language areas using the superselective infusion of propofol.

OBSERVATIONS

A 32-year-old right-handed female presented with drug-resistant epilepsy. Comprehensive epilepsy evaluation suggested that the epileptic foci involved the whole left frontal lobe but provided less evidence of structural abnormality. To estimate the extent of functional deterioration likely to be caused by an extended left frontal lobectomy, the authors evaluated segmented cortical function in the ipsi- and contralateral hemispheres by the superselective infusion of propofol into the branches of the intracranial artery. The results revealed bilateral and asymmetrical localization of language function because the patient presented with different components of aphasia in each hemisphere. Based on the authors’ assessment of her functional tolerance, an extended left frontal lobectomy was performed and resulted in neurological deficits within the anticipated range.

LESSONS

An accurate understanding of the correlations between vascular and functional anatomy and the highly specific evaluation of language function provides more advanced presurgical assessment, allowing more tailored planning of cortical resection.

ABBREVIATIONS

EEG = electroencepholography; ECS = electrical cortical stimulation; FDG-PET = fluorodeoxyglucose positron emission tomography; fMRI = functional magnetic resonance imaging; ICA = internal carotid artery; IQ = intelligence quotient; LT-VEEG = long-term video electroencephalography; MCA = middle cerebral artery; MOGHE = malformation of cortical development with oligodendroglial hyperplasia and epilepsy; MRI = magnetic resonance imaging; OLC = oligodendrocyte-like cell; ssWada = superselective Wada; WAB = Western Aphasia Battery

Planning for resection surgery of intra-axial lesions must consider the postsurgical deterioration of brain functions. The strategy for well-localized or circumscribed functions makes avoiding such risk easy or allows one to optimize the balance between a good outcome and functional deterioration. However, for functions with an obscure localization or diffuse distributions such as language, there is difficulty in analyzing risks even with invasive and noninvasive methods.1

The left hemisphere is considered the language-dominant hemisphere in most right-handed people. Several methods, including functional magnetic resonance imaging (fMRI) and the internal carotid artery (ICA)-Wada test, have been developed to explore the lateralization of language function between the two hemispheres but not the localization of function. Both fMRI2 and the ICA-Wada test3 have demonstrated atypical language function approximately on both hemispheres, but they could not be applied directly for evaluating the localization of brain function for any tailored cortical resection in epilepsy surgery. The fMRI study for determining language dominancy in presurgical risk evaluation could fail to anticipate postoperative neurological aggravation, especially in the case of atypical language dominancy.4 Functional shifts can occur if the brain lesion was present congenitally or from an early stage of development, so the individual evaluation of functional localization is important but difficult.5

We previously developed the superselective Wada (ssWada) to evaluate voluntary functions in specific brain regions by the superselective infusion of an anesthetic agent from the intracranial artery.6,7 The ssWada can induce a focal neurological deficit corresponding to the area perfused by the selected artery without inducing unwanted consciousness disturbance, which mainly results from unintended distribution to perforating arteries. Consequently, the subject can directly explain their experience and symptoms, which provides a more accurate simulation of likely postsurgical neurological symptoms. Compared with hemispheric dominancy evaluated by the ICA-Wada test, ssWada enables us to discuss the more detailed localization of brain function even within the hemisphere.

We used the ssWada to demonstrate bilateral but asymmetrical localization of language function by superselective infusion to the subdivisions of the middle cerebral artery (MCA) in a patient with epilepsy with suspected mild dysplasia of brain structure in an early stage of life. The findings deeply affected surgical indications.

Illustrative Case

History and Presentation

A 32-year-old female patient with intractable epilepsy first presented with seizure manifesting as West syndrome at age 1 year and was treated with medication, resulting in seizure remission for 20 years. Her seizures relapsed and became drug resistant, so she was evaluated for epilepsy surgery at age 25 years. She was diagnosed with left temporal lobe epilepsy without magnetic resonance imaging (MRI) abnormality and was treated with anterior temporal lobectomy with amygdalohippocampectomy on the left side. However, her seizures did not change, so additional evaluation was scheduled 6 years later.

Presurgical Evaluation

Comprehensive evaluation for surgical indications was performed including long-term video electroencephalography (LT-VEEG), 3-T MRI, fluorodeoxyglucose positron emission tomography (FDG-PET), and neuropsychological evaluation. LT-VEEG showed behavioral arrest followed by automatism with impaired awareness seizure and electroencephalography (EEG) change in the left hemisphere. MRI revealed reduced corticomedullary differentiation in the anterior half of the left hemisphere, which had not been previously identified (Fig. 1 upper). The lesion involved the left lateral frontal area, orbitofrontal area, anterior cingulate area, paracentral cortex, and frontal insulo-opercular cortex. FDG-PET detected no focal glucose hypometabolism (Fig. 1 lower). fMRI could not present the language task-related activity because of the metal artifact inserted at the previous craniotomy and anterior temporal lobectomy, resulting in inconclusive findings on determining language dominancy. The patient was right-handed with Edinburgh Handedness Inventory laterality quotient of +100.8 Her cognitive function was preserved at a higher level with a full intelligence quotient (IQ) of 91, verbal IQ of 94, performance IQ of 90 according to the Wechsler Adult Intelligence Scale III; verbal memory of 123, visual memory of 104, general memory of 120, attention and concentration of 81, and delayed recall of 121 according to the Wechsler Memory Scale-Revised; and an aphasia quotient of 95.6, spontaneous speech of 20, auditory verbal comprehension of 8.9, repetition of 9.6, naming of 9.4, reading of 8.4, and writing of 10 according to the Western Aphasia Battery (WAB). On the basis of these findings, we considered that the possible epileptogenic zone involved the left frontal and parietal lobes and the surrounding tissue, suggesting a high risk of language function loss after extended resection. Therefore, we tried to evaluate regional function in both the suggested epileptogenic zone, surrounding areas, and the homologous region in the contralateral hemisphere by using the ssWada presurgically.

FIG. 1
FIG. 1

Upper: Presurgical fluid-attenuated inversion recovery MRI revealing blurring of the gray-white matter interface (arrowheads). Lower: Presurgical FDG-PET fusion images showing no focal hypometabolism.

ssWada Test

All procedures were performed in an endovascular neurosurgical suite. Diagnostic cerebral angiography and whole-body heparinization with the activated clotting time extended to double from the baseline, and then a 6-Fr guiding catheter was introduced as the guiding catheter into the cervical segment of the ICA proximal to the targeted area. Superselective catheterization was performed to pass a Yamato Heal-ex 10 & 18 (Technocrat Corp.) microcatheter tip to the intracranial artery. After confirming the perfusion area by superselective angiography, propofol 1 mg/mL was infused at 1 mL/sec after baseline evaluation of the neurological findings. The amount of infused propofol was 7.5 mg into the superior or inferior division of the MCA or 10 mg into the M1 segment of the MCA. Scalp EEG was monitored to confirm electrophysiological changes during drug infusion. Cognitive neurologists evaluated all neurological symptoms both pre- and postinfusion. The test battery was used for the evaluation of language function to test sequential speech, listening comprehension, repetition, naming, reading comprehension, reading aloud, and writing. The patient was asked to describe the symptoms and experiences during infusion after the recovery of neurological symptoms.

We confirmed the correlations between vascular anatomy and perfusion territory of the intracranial arteries in advance (Figs. 2A and 3A). The anterior language area in the left hemisphere consists of the inferior frontal gyrus perfused by two branches of the MCA, the pars orbitalis and pars triangularis perfused by the early frontal branch (Fig. 2B,D, E, and F), and the pars opercularis perfused by the M2 superior division (Fig. 2D–F). The posterior language area consists of the posterior part of the superior temporal gyrus perfused by only the M2 inferior division (Fig. 2C and F). First, the injection site at the M1 proximal segment was selected to induce symptoms of the anterior language area including the inferior frontal gyrus and surrounding structures. The M1 segment proximal to the bifurcation of the early frontal branch is the most distal part including these branches (Fig. 2D–F). Second, the injection site at the M2 inferior division was selected to induce symptoms of the posterior language area including the posterior part of the superior temporal gyrus and surrounding structures (Fig. 2D–F).

FIG. 2
FIG. 2

Relationships between vascular and cortical anatomy based on drug distribution in the left ICA territory. Superselective catheterization of the total left ICA territory (A) enabled selective angiography of the M2 superior division (B) and the M2 inferior division (C) of the MCA. Vascular anatomy of the left ICA territory is shown with colored dotted lines (D and E) and cortical area (F). Filled and open arrowheads indicate the infusion sites that distribute drug to the minimum area to elicit the neurological symptom corresponding to the total inferior frontal gyrus as an anterior language area (dashed purple line, F), and the open arrowhead shows the posterior superior temporal gyrus as a posterior language area.

FIG. 3
FIG. 3

Relationships between vascular and cortical anatomy based on drug distribution in the right ICA territory. Superselective catheterization of the total right ICA territory (A) enabled selective angiography of the M2 superior division (B) and the M2 inferior division (C) of the MCA. Vascular anatomy of the right ICA territory is shown with colored dotted lines (D and E) and cortical area (F). Filled arrowheads indicate the infusion sites that distribute drug to the minimum area to elicit the neurological symptom corresponding to the total inferior frontal gyrus as an anterior language area, and the open arrowhead shows the posterior superior temporal gyrus as a posterior language area.

These procedures were repeated in the right hemisphere (Fig. 3B) by selecting the M2 superior division (Fig. 3B,D, and E) and M2 inferior division (Fig. 3C,D, E, and F). These arteries perfused the anterior and posterior language areas corresponding to the structures in the contralateral hemisphere (Fig. 3E and F). EEG changes within seconds after infusion of propofol were confirmed in all vessels.

The results of the tests are given in Table 1. Infusion from the M1 segment of the left MCA induced language symptoms of phonological paraphasia, difficulty in repeating words and reading aloud, and writing without disturbance in reading comprehension and memory function. The patient also reported hemiparesis of the right limbs with anosognosia and unilateral hemispatial neglect to the right side. In contrast, infusion from the M2 inferior trunk of the left MCA induced no language symptoms. On the contralateral side, infusion from the M2 superior trunk of the right MCA induced speech arrest with preserved reading comprehension and acalculia. The patient also reported hemiparesis of the left limbs and unilateral hemispatial neglect to the left side. Infusion from the M2 inferior trunk of the right MCA induced difficulty in repeating words and reading aloud. We interpreted these results as showing that language function was dominant in the right hemisphere but was bilaterally localized with complementary components of language function. That meant that the patient could tolerate extended frontal lobectomy.

TABLE 1

Evaluated neurological symptoms before and after propofol infusion

Tasks & Neurological FindingsInfusion Site; Responsible Areas
Lt M2 Inferior; TemporalLt M1; Frontal, Parietal, TemporalRt M2 Inferior; Parietal, TemporalRt M2 Superior; Frontal, Parietal
Sequential speechNCNCNCNC
ComprehensionNCNCNCNC
RepetitionNCNot ableNot ableNot able
Read aloudNCNot ableAble w/ dysarthriaNot able
Read comprehensionNCNCNCNC
Reading wordsNCPhonemic paraphasiaAble w/ dysarthriaSpeech arrest
NamingNCPhonemic paraphasiaAble w/ dysarthriaSpeech arrest
Writing; KanjiNCAble w/ difficultyNCNC
Writing; KanaNCAble w/ difficultyNCNC
Finger postureNCNCNCNC
Recall wordNCNCNCNC
Recall pictureNCNCNCNC
Recall writingNCNCNCNC
Recognition wordNCNCDeclinedDeclined
Recognition pictureNCNCNCNC
Recognition figureNCNCNCNC
False alarm wordOneNoneTwoTwo
False alarm pictureNoneNoneNoneNone
UHNNoneUHN to rtNoneUHN to lt
InsightNCMild speech difficulty, need more time into voiceNCSpeech difficulty
Other findingsNoneRt hemiparesisTongue paresisLt hemiparesis, tongue paresis

inferior = inferior division; NC = no change; superior = superior division; UHN = unilateral hemispatial neglect.

Intracranial Electrode Study and Resective Surgery

Depth and subdural electrodes were implanted in the left hemisphere for detection of the epileptogenic zone and functional mapping (Fig. 4A and B). The lateral frontal, basal frontal, and medial frontal lobes, and insula and operculum of the frontal, parietal, and temporal lobes were studied. Interictal epileptic activities were observed in the middle frontal gyrus, frontal opercular cortex, insula, precentral gyrus, and postcentral gyrus (Fig. 4B). EEG changes at seizure onset had diffuse or multiple origins mainly in the frontal lobe. Functional mapping of the language area with electrical cortical stimulation (ECS) revealed a slight delay of speech in the naming task at multiple electrodes in the middle frontal gyrus (Fig. 4B). However, ECS of the inferior frontal gyrus showed no neurological symptom.

FIG. 4
FIG. 4

A: Skull radiographs showing the intracranial electrodes placed for mapping. B: The schema represents the results of mapping. Each circle represents intracranial electrodes. Yellow-marked circles represent electrodes that detected interictal epileptic activities. Circles connected by lines detected language function by electrical cortical stimulation. Circles connected by red lines represent stimulation resulting in a slight delay of speech in the naming task. C: Postoperative MRI revealing the extended frontal lobectomy and insulectomy with preservation of the primary motor area.

Therefore, we considered that the functional risk of extended frontal lobectomy with preservation of the precentral gyrus would be acceptable because the results of functional mapping with intracranial electrodes and the ssWada were concordant. Both findings also suggested that at least several components of language function were located in both the left frontal lobe and the contralateral hemisphere (Table 1).

We performed a tailored cortical resection that contained the inferior frontal gyrus, middle frontal gyrus, and orbitofrontal, anterior cingulate, dorsolateral prefrontal, and insulo-opercular cortices of the left hemisphere. The precentral and postcentral gyri were preserved to avoid the risk of damage to sensorimotor function (Fig. 4C). The patient presented with word-finding difficulty just after the surgery, but then she improved. Her Frontal Assessment Battery score was 15/18 by 2 weeks after surgery, so that her activities of daily life were not affected. Her seizures improved in frequency to months, resulting in Engel class IIIa outcome. Follow-up neuropsychological assessment 1 year after the surgery showed a mild decline of aphasia quotient of 87.2 and spontaneous speech of 16 but preserved auditory verbal comprehension of 8.8, repetition of 9.6, naming of 9.2, reading of 8.4, and writing of 10 with the WAB.

Pathology

Luxol fast blue with hematoxylin and eosin staining of the surgical specimens corresponding to the MRI lesion revealed an accumulation of oligodendrocyte-like cells (OLCs) in the subcortical white matter. The boundary zone between cortex and white matter was obscured by infiltration of the OLCs into the deeper layer of the cortex with myelin pallor. Perivascular aggregation of OLCs also scattered in the subcortical white matter. These findings were concordant with mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE).

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Resective surgery for drug-resistant epilepsy is widely accepted as an effective treatment for intractable epilepsy. However, the procedure involves resection of the brain itself, so carries the risk of serious neurological deficits such as cognitive9 and language dysfunction that can affect quality of life.10 A previous retrospective cohort study found that patients who had undergone unilateral frontal lobectomy showed no more than mild cognitive complications such as declines in intelligence, working memory, and language function in the dominant hemisphere.11 Unfortunately, accurate presurgical assessment of cortical functions is difficult considering individual variations.12,13 Conflicting fMRI findings of language function lateralization were reported in one of three epilepsy patients.14 The analysis of blood oxygen level-dependent signal essentially depends on the thresholding, so the criticality of cortex showing bilateral activity is hard to assess. So even if fMRI can reveal the dominant hemisphere for language function, functional localization in the specific area cannot be guaranteed in every individual.4,15 The most noninvasive method to estimate language function can suggest relative dominance of hemispheres or integrated information presumed from the activities of multiple regions.16,17 Therefore, we introduced intracranial electrodes to evaluate more detailed cortical functions. This method can identify the language-related area by task-related activities18 or symptoms induced by ECS with millimeter to centimeter accuracy,15,19,20 but we could not estimate the function of larger masses of the brain even after integrating ECS results for the planning of more extensive resection.21 In other words, we purposed the simulation of postsurgical deficit after extended frontal lobectomy, not by rough result of ICA-Wada for hemispheric dominancy or by detailed result of ECS for gyral function. Although such a methodology could have been applied to selected patients because of a high-risk of superselective catheterization to the intracranial artery, recent advances in neuroendovascular techniques enabled the detailed evaluation of functional localization in the higher level.22,23

Observations

We believed that language function was located in both hemispheres in our case for the following reasons. The propofol injection into left M1 only resulted mild dysfunction in speech and writing and preserved comprehension. A previous study of a patient with a massive left-hemisphere lesion that involved the whole language area showed only mild fluent aphasia after resection, which suggested the bilateral location of language function.24 The ssWada can evaluate more detailed localization of language areas,25 so we used the ssWada to reveal the real function in the left frontal lobe and complementary functions in the homologous right frontal lobe. The indications and target vessels for the ssWada were selected only to determine the resection area. The result was unique, with asymmetrical and different language symptoms of verbal paraphasia in the left frontal lobe and speech arrest in the right frontal lobe, showing the areas responsible for anterior language functions suppressed by infusion.

Anesthesia in the left temporoparietal area did not induce language abnormality, whereas that in the right temporoparietal area induced difficulty in repetition and reading, demonstrating that the posterior language area is on the right side. These unique findings demonstrated asymmetrical language functions located in both hemispheres. Several fMRI studies have suggested bilateral locations of language function11 but provided only indirect evidence for cortical resection of the responsible areas. In contrast, ICA-Wada test can directly elicit the symptoms as a simulation of focal neurological deficit. However, fundamental symptoms such as disturbance of consciousness will complicate interpretation of induced symptoms related to language function in the ICA-Wada test.26,27 The ssWada has advantages in selectivity and the avoidance of consciousness disturbance in patients with malignant glioma in the left inferior frontal gyrus.7

Functional mapping by ECS can directly evaluate the regional functions of the brain using intracranial electrodes28–30 or awake craniotomy.31,32 However, the evaluation is based on the limited volume of ECS. Consequently, whether the cumulative results of electrical stimulation trials are comparable to the expected outcomes of the resection of a larger volume is uncertain.33 In our patient, considering only the results of the ECS study, in which language impairment was induced by left frontal stimulation, we might conclude that resection of the left frontal lobe is not indicated (Fig. 4B). The presurgical information of ssWada encouraged the extended frontal lobectomy by allowing us to anticipate and avoid a postsurgical severe decline of language function.

MOGHE is a pathological finding found in pediatric patients who have undergone frontal lobectomy.34–36 Atypical localization suggesting a functional shift has been reported in patients with brain lesions, such as tumor or epileptic focus during the developmental stages.2,37 Therefore, we propose that the preceding abnormality of the brain occurring in the early phase of brain development facilitated the observed functional shift and resulted in the bilateral and asymmetrical localizations of language function in our patient.

We think that the ssWada has three advantages. First, ssWada has higher selectivity for the brain functions than the ICA-Wada test. Our case illustrates the selectivity of the ssWada for accurately localizing specific language functions. Second, the test subject suffers less consciousness disturbance or dysarthria that can disturb the accurate differentiation of the language function components. The ssWada can avoid unwanted infusion into other cortical branches and perforating arteries that could cause consciousness disturbance or dysarthria.3,6 Third, the test subject can report the subjective symptom because of less consciousness disturbance and can discuss and consider the postsurgical risk based on both objective findings and subjective experiences. Consideration of the postoperative neurological deficit is as important as the seizure outcome.38,39 The subjective information obtained in the ssWada can widen the surgical indication both through more detailed functional delineation and through the patient’s acceptance of neurological decline based on subjective experience.

The ssWada also has several disadvantages and limitations. First, the test requires more complicated endovascular techniques and evaluations of neurological changes. We assigned both endovascular neurosurgeons and behavioral neurologists to discuss the relationship between the perfusion territory of the selected artery and the responsible functions prior to the procedure. The present case required complete assessment of the entire inferior frontal gyrus as an anterior language area for risk evaluation of an extended cortectomy involving the language area (Fig. 2D–F). Consequently, a comprehensive understanding of the vascular anatomy, functional anatomy, and neuroendovascular technique is required in this method. Second, the ssWada may increase the procedural risk due to intracranial manipulation of the microcatheter. Previous studies have reported the relatively high risk of superselective catheterization for the infusion of anesthetic agents.22 However, the development of improved devices has increased the safety of neuroendovascular procedures even in the cortical artery, in which the technical success rate has been 97.9% to 98.1% in asymptomatic lesions,23 so we believe that the similar procedure of superselective injection of propofol can be performed safely. Third, the absence of neurological changes can be difficult to establish because the amount of infused agent is small, an unexpected shift of the catheter tip can occur, and EEG changes are less pronounced than in the ICA-Wada test. Consequently, further validation of the endovascular procedures and evaluation protocols is necessary for the extended application of the ssWada to other intracranial regions.

Lessons

Extended resection of large volumes of brain is often difficult to consider in patients with highly preserved brain functions. Superselective infusion of propofol into the intracranial arteries perfusing the anterior and posterior language areas can induce deficits in the different corresponding components of language function and the patient can recognize the results subjectively, thus allowing extended left frontal lobectomy without affecting patient quality of life. The accurate localization of brain function is useful for both predicting postoperative neurological change and obtaining the patient’s acceptance of the surgery.

Author Contributions

Conception and design: Osawa, Niizuma, Narita, Nakasato. Acquisition of data: Osawa, K Suzuki, Kakinuma, Ukishiro, Niizuma, Narita. Analysis and interpretation of data: Osawa, K Suzuki, Kakinuma, H Suzuki, Narita, Nakasato. Drafting the article: Osawa, Otomo, Narita, Nakasato. Critically revising the article: K Suzuki, Kakinuma, H Suzuki, Niizuma, Narita, Nakasato. Reviewed submitted version of manuscript: Osawa, Kakinuma, H Suzuki, Niizuma, Narita, Nakasato, Tominaga. Approved the final version of the manuscript on behalf of all authors: Osawa. Statistical analysis: Narita. Administrative/technical/material support: Kakinuma, Narita. Study supervision: K Suzuki, Narita, Tominaga.

References

  • 1

    Herbet G, Duffau H. Revisiting the functional anatomy of the human brain: toward a meta-networking theory of cerebral functions. Physiol Rev. 2020;100(3):11811228.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Yuan W, Szaflarski JP, Schmithorst VJ, et al. fMRI shows atypical language lateralization in pediatric epilepsy patients. Epilepsia. 2006;47(3):593600.

  • 3

    Mikuni N, Takayama M, Satow T, et al. Evaluation of adverse effects in intracarotid propofol injection for Wada test. Neurology. 2005;65(11):18131816.

  • 4

    Benjamin CFA, Li AX, Blumenfeld H, et al. Presurgical language fMRI: clinical practices and patient outcomes in epilepsy surgical planning. Hum Brain Mapp. 2018;39(7):27772785.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Szaflarski JP, Binder JR, Possing ET, McKiernan KA, Ward BD, Hammeke TA. Language lateralization in left-handed and ambidextrous people: fMRI data. Neurology. 2002;59(2):238244.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Fujii M, Miyachi S, Matsubara N, et al. Selective propofol injection into the M1 segment of the middle cerebral artery (MCA Wada test) reduces adverse effects and enhances the reliability of the Wada test for determining speech dominance. World Neurosurg. 2011;75(3–4):503508.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Yamashita S, Saito R, Osawa SI, et al. A super-selective Wada test successfully detected an artery that supplied Broca’s area in a case of left frontal lobe glioblastoma: technical case report. Neurol Med Chir (Tokyo). 2021;61(11):661666.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971;9(1):97113.

  • 9

    Kamalboor H, Alhindi H, Alotaibi F, Althubaiti I, Alkhateeb M. Frontal disconnection surgery for drug-resistant epilepsy: outcome in a series of 16 patients. Epilepsia Open. 2020;5(3):475486.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Krauss GL, Fisher R, Plate C, et al. Cognitive effects of resecting basal temporal language areas. Epilepsia. 1996;37(5):476483.

  • 11

    Busch RM, Floden DP, Ferguson L, et al. Neuropsychological outcome following frontal lobectomy for pharmacoresistant epilepsy in adults. Neurology. 2017;88(7):692700.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Berl MM, Zimmaro LA, Khan OI, et al. Characterization of atypical language activation patterns in focal epilepsy. Ann Neurol. 2014;75(1):3342.

  • 13

    Połczyńska MM, Benjamin CFA, Moseley BD, et al. Role of the Wada test and functional magnetic resonance imaging in preoperative mapping of language and memory: two atypical cases. Neurocase. 2015;21(6):707720.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Omisade A, O’Grady C, Sadler RM. Divergence between functional magnetic resonance imaging and clinical indicators of language dominance in preoperative language mapping. Hum Brain Mapp. 2020;41(14):38673877.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Arya R, Roth C, Leach JL, et al. Neuropsychological outcomes after resection of cortical sites with visual naming associated electrocorticographic high-gamma modulation. Epilepsy Res. 2019;151:1723.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Seghier ML. Laterality index in functional MRI: methodological issues. Magn Reson Imaging. 2008;26(5):594601.

  • 17

    Wegrzyn M, Mertens M, Bien CG, Woermann FG, Labudda K. Quantifying the confidence in fMRI-based language lateralisation through laterality index deconstruction. Front Neurol. 2019;10:655.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Ervin B, Buroker J, Rozhkov L, et al. High-gamma modulation language mapping with stereo-EEG: A novel analytic approach and diagnostic validation. Clin Neurophysiol. 2020;131(12):28512860.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Arya R, Ervin B, Dudley J, et al. Electrical stimulation mapping of language with stereo-EEG. Epilepsy Behav. 2019;99:106395.

  • 20

    Osawa SI, Suzuki K, Asano E, et al. Causal involvement of medial inferior frontal gyrus of non-dominant hemisphere in higher order auditory perception: A single case study. Cortex. 2023;163:5765.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Liu Y, Chen G, Chen J, et al. Individualized stereoelectroencephalography evaluation and navigated resection in medically refractory pediatric epilepsy. Epilepsy Behav. 2020;112:107398.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Loddenkemper T, Morris HH, Möddel G. Complications during the Wada test. Epilepsy Behav. 2008;13(3):551553.

  • 23

    Tawk RG, Tummala RP, Memon MZ, Siddiqui AH, Hopkins LN, Levy EI. Utility of pharmacologic provocative neurological testing before embolization of occipital lobe arteriovenous malformations. World Neurosurg. 2011;76(3–4):276281.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Kasselimis D, Potagas C, Simos P, Evdokimidis I, Whitaker H. Mixed language dominance: insights from a case of unexpected fluent aphasia with semantic jargon resulting from massive left perisylvian lesion. Neurocase. 2018;24(1):1015.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Kakinuma K, Osawa SI, Hosokawa H, et al. Determination of language areas in patients with epilepsy using the super-selective Wada test. IBRO Neurosci Rep. 2022;13:156163.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Kundu B, Rolston JD, Grandhi R. Mapping language dominance through the lens of the Wada test. Neurosurg Focus. 2019;47(3):E5.

  • 27

    Kurthen M, Solymosi L, Linke D. The intracarotid amobarbital test. Neuroradiologic and neuropsychologic aspects. Article in German. Radiologe. 1993;33(4):204212.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Nakai Y, Jeong JW, Brown EC, et al. Three- and four-dimensional mapping of speech and language in patients with epilepsy. Brain. 2017;140(5):13511370.

  • 29

    Grande KM, Ihnen SKZ, Arya R. Electrical stimulation mapping of brain function: a comparison of subdural electrodes and stereo-EEG. Front Hum Neurosci. 2020;14:611291.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Sinai A, Crone NE, Wied HM, Franaszczuk PJ, Miglioretti D, Boatman-Reich D. Intracranial mapping of auditory perception: event-related responses and electrocortical stimulation. Clin Neurophysiol. 2009;120(1):140149.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Szelényi A, Bello L, Duffau H, et al. Intraoperative electrical stimulation in awake craniotomy: methodological aspects of current practice. Neurosurg Focus. 2010;28(2):E7.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Kumabe T, Sato K, Iwasaki M, et al. Summary of 15 years experience of awake surgeries for neuroepithelial tumors in tohoku university. Neurol Med Chir (Tokyo). 2013;53(7):455466.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Sperber C. The strange role of brain lesion size in cognitive neuropsychology. Cortex. 2022;146:216226.

  • 34

    Schurr J, Coras R, Rössler K, et al. Mild malformation of cortical development with oligodendroglial hyperplasia in frontal lobe epilepsy: a new clinico-pathological entity. Brain Pathol. 2017;27(1):2635.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Garganis K, Kokkinos V, Zountsas B, Dinopoulos A, Coras R, Blümcke I. Temporal lobe “plus” epilepsy associated with oligodendroglial hyperplasia (MOGHE). Acta Neurol Scand. 2019;140(4):296300.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Verentzioti A, Blumcke I, Alexoudi A, et al. Epileptic patient with mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE): a case report and review of the literature. Case Rep Neurol Med. 2019;2019:9130780.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Krieg SM, Sollmann N, Hauck T, et al. Functional language shift to the right hemisphere in patients with language-eloquent brain tumors. PLoS One. 2013;8(9):e75403.

  • 38

    Iwasaki M, Uematsu M, Nakayama T, et al. Parental satisfaction and seizure outcome after corpus callosotomy in patients with infantile or early childhood onset epilepsy. Seizure. 2013;22(4):303305.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Josephson CB, Engbers JDT, Sajobi TT, et al. Predicting postoperative epilepsy surgery satisfaction in adults using the 19-item Epilepsy Surgery Satisfaction Questionnaire and machine learning. Epilepsia. 2021;62(9):21032112.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
  • FIG. 1

    Upper: Presurgical fluid-attenuated inversion recovery MRI revealing blurring of the gray-white matter interface (arrowheads). Lower: Presurgical FDG-PET fusion images showing no focal hypometabolism.

  • FIG. 2

    Relationships between vascular and cortical anatomy based on drug distribution in the left ICA territory. Superselective catheterization of the total left ICA territory (A) enabled selective angiography of the M2 superior division (B) and the M2 inferior division (C) of the MCA. Vascular anatomy of the left ICA territory is shown with colored dotted lines (D and E) and cortical area (F). Filled and open arrowheads indicate the infusion sites that distribute drug to the minimum area to elicit the neurological symptom corresponding to the total inferior frontal gyrus as an anterior language area (dashed purple line, F), and the open arrowhead shows the posterior superior temporal gyrus as a posterior language area.

  • FIG. 3

    Relationships between vascular and cortical anatomy based on drug distribution in the right ICA territory. Superselective catheterization of the total right ICA territory (A) enabled selective angiography of the M2 superior division (B) and the M2 inferior division (C) of the MCA. Vascular anatomy of the right ICA territory is shown with colored dotted lines (D and E) and cortical area (F). Filled arrowheads indicate the infusion sites that distribute drug to the minimum area to elicit the neurological symptom corresponding to the total inferior frontal gyrus as an anterior language area, and the open arrowhead shows the posterior superior temporal gyrus as a posterior language area.

  • FIG. 4

    A: Skull radiographs showing the intracranial electrodes placed for mapping. B: The schema represents the results of mapping. Each circle represents intracranial electrodes. Yellow-marked circles represent electrodes that detected interictal epileptic activities. Circles connected by lines detected language function by electrical cortical stimulation. Circles connected by red lines represent stimulation resulting in a slight delay of speech in the naming task. C: Postoperative MRI revealing the extended frontal lobectomy and insulectomy with preservation of the primary motor area.

  • 1

    Herbet G, Duffau H. Revisiting the functional anatomy of the human brain: toward a meta-networking theory of cerebral functions. Physiol Rev. 2020;100(3):11811228.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Yuan W, Szaflarski JP, Schmithorst VJ, et al. fMRI shows atypical language lateralization in pediatric epilepsy patients. Epilepsia. 2006;47(3):593600.

  • 3

    Mikuni N, Takayama M, Satow T, et al. Evaluation of adverse effects in intracarotid propofol injection for Wada test. Neurology. 2005;65(11):18131816.

  • 4

    Benjamin CFA, Li AX, Blumenfeld H, et al. Presurgical language fMRI: clinical practices and patient outcomes in epilepsy surgical planning. Hum Brain Mapp. 2018;39(7):27772785.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Szaflarski JP, Binder JR, Possing ET, McKiernan KA, Ward BD, Hammeke TA. Language lateralization in left-handed and ambidextrous people: fMRI data. Neurology. 2002;59(2):238244.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Fujii M, Miyachi S, Matsubara N, et al. Selective propofol injection into the M1 segment of the middle cerebral artery (MCA Wada test) reduces adverse effects and enhances the reliability of the Wada test for determining speech dominance. World Neurosurg. 2011;75(3–4):503508.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Yamashita S, Saito R, Osawa SI, et al. A super-selective Wada test successfully detected an artery that supplied Broca’s area in a case of left frontal lobe glioblastoma: technical case report. Neurol Med Chir (Tokyo). 2021;61(11):661666.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971;9(1):97113.

  • 9

    Kamalboor H, Alhindi H, Alotaibi F, Althubaiti I, Alkhateeb M. Frontal disconnection surgery for drug-resistant epilepsy: outcome in a series of 16 patients. Epilepsia Open. 2020;5(3):475486.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Krauss GL, Fisher R, Plate C, et al. Cognitive effects of resecting basal temporal language areas. Epilepsia. 1996;37(5):476483.

  • 11

    Busch RM, Floden DP, Ferguson L, et al. Neuropsychological outcome following frontal lobectomy for pharmacoresistant epilepsy in adults. Neurology. 2017;88(7):692700.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Berl MM, Zimmaro LA, Khan OI, et al. Characterization of atypical language activation patterns in focal epilepsy. Ann Neurol. 2014;75(1):3342.

  • 13

    Połczyńska MM, Benjamin CFA, Moseley BD, et al. Role of the Wada test and functional magnetic resonance imaging in preoperative mapping of language and memory: two atypical cases. Neurocase. 2015;21(6):707720.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Omisade A, O’Grady C, Sadler RM. Divergence between functional magnetic resonance imaging and clinical indicators of language dominance in preoperative language mapping. Hum Brain Mapp. 2020;41(14):38673877.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Arya R, Roth C, Leach JL, et al. Neuropsychological outcomes after resection of cortical sites with visual naming associated electrocorticographic high-gamma modulation. Epilepsy Res. 2019;151:1723.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Seghier ML. Laterality index in functional MRI: methodological issues. Magn Reson Imaging. 2008;26(5):594601.

  • 17

    Wegrzyn M, Mertens M, Bien CG, Woermann FG, Labudda K. Quantifying the confidence in fMRI-based language lateralisation through laterality index deconstruction. Front Neurol. 2019;10:655.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Ervin B, Buroker J, Rozhkov L, et al. High-gamma modulation language mapping with stereo-EEG: A novel analytic approach and diagnostic validation. Clin Neurophysiol. 2020;131(12):28512860.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Arya R, Ervin B, Dudley J, et al. Electrical stimulation mapping of language with stereo-EEG. Epilepsy Behav. 2019;99:106395.

  • 20

    Osawa SI, Suzuki K, Asano E, et al. Causal involvement of medial inferior frontal gyrus of non-dominant hemisphere in higher order auditory perception: A single case study. Cortex. 2023;163:5765.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Liu Y, Chen G, Chen J, et al. Individualized stereoelectroencephalography evaluation and navigated resection in medically refractory pediatric epilepsy. Epilepsy Behav. 2020;112:107398.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Loddenkemper T, Morris HH, Möddel G. Complications during the Wada test. Epilepsy Behav. 2008;13(3):551553.

  • 23

    Tawk RG, Tummala RP, Memon MZ, Siddiqui AH, Hopkins LN, Levy EI. Utility of pharmacologic provocative neurological testing before embolization of occipital lobe arteriovenous malformations. World Neurosurg. 2011;76(3–4):276281.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Kasselimis D, Potagas C, Simos P, Evdokimidis I, Whitaker H. Mixed language dominance: insights from a case of unexpected fluent aphasia with semantic jargon resulting from massive left perisylvian lesion. Neurocase. 2018;24(1):1015.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Kakinuma K, Osawa SI, Hosokawa H, et al. Determination of language areas in patients with epilepsy using the super-selective Wada test. IBRO Neurosci Rep. 2022;13:156163.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Kundu B, Rolston JD, Grandhi R. Mapping language dominance through the lens of the Wada test. Neurosurg Focus. 2019;47(3):E5.

  • 27

    Kurthen M, Solymosi L, Linke D. The intracarotid amobarbital test. Neuroradiologic and neuropsychologic aspects. Article in German. Radiologe. 1993;33(4):204212.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Nakai Y, Jeong JW, Brown EC, et al. Three- and four-dimensional mapping of speech and language in patients with epilepsy. Brain. 2017;140(5):13511370.

  • 29

    Grande KM, Ihnen SKZ, Arya R. Electrical stimulation mapping of brain function: a comparison of subdural electrodes and stereo-EEG. Front Hum Neurosci. 2020;14:611291.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Sinai A, Crone NE, Wied HM, Franaszczuk PJ, Miglioretti D, Boatman-Reich D. Intracranial mapping of auditory perception: event-related responses and electrocortical stimulation. Clin Neurophysiol. 2009;120(1):140149.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Szelényi A, Bello L, Duffau H, et al. Intraoperative electrical stimulation in awake craniotomy: methodological aspects of current practice. Neurosurg Focus. 2010;28(2):E7.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Kumabe T, Sato K, Iwasaki M, et al. Summary of 15 years experience of awake surgeries for neuroepithelial tumors in tohoku university. Neurol Med Chir (Tokyo). 2013;53(7):455466.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Sperber C. The strange role of brain lesion size in cognitive neuropsychology. Cortex. 2022;146:216226.

  • 34

    Schurr J, Coras R, Rössler K, et al. Mild malformation of cortical development with oligodendroglial hyperplasia in frontal lobe epilepsy: a new clinico-pathological entity. Brain Pathol. 2017;27(1):2635.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Garganis K, Kokkinos V, Zountsas B, Dinopoulos A, Coras R, Blümcke I. Temporal lobe “plus” epilepsy associated with oligodendroglial hyperplasia (MOGHE). Acta Neurol Scand. 2019;140(4):296300.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Verentzioti A, Blumcke I, Alexoudi A, et al. Epileptic patient with mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE): a case report and review of the literature. Case Rep Neurol Med. 2019;2019:9130780.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Krieg SM, Sollmann N, Hauck T, et al. Functional language shift to the right hemisphere in patients with language-eloquent brain tumors. PLoS One. 2013;8(9):e75403.

  • 38

    Iwasaki M, Uematsu M, Nakayama T, et al. Parental satisfaction and seizure outcome after corpus callosotomy in patients with infantile or early childhood onset epilepsy. Seizure. 2013;22(4):303305.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Josephson CB, Engbers JDT, Sajobi TT, et al. Predicting postoperative epilepsy surgery satisfaction in adults using the 19-item Epilepsy Surgery Satisfaction Questionnaire and machine learning. Epilepsia. 2021;62(9):21032112.

    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 628 628 114
PDF Downloads 346 346 37
EPUB Downloads 0 0 0