To the best of our knowledge, this is the first study to evaluate the time-dependent improvements in visual field deficits after awake craniotomy for supratentorial gliomas. Moreover, we showed by anatomo-functional analysis that intraoperative DES to identify and preserve the optic radiation appears to be a reliable and effective technique to avoid permanent hemianopsia with visual plasticity in awake craniotomy for gliomas.
Visual Phenomena Elicited by Direct Electrical Stimulation
In the current study, three visual symptoms were intraoperatively observed: phosphene, blurred vision, and hallucinations, as reported previously (Gras-Combe et al. 2012). Contrary to the observations of the present study, blurred vision has been reported to be the most frequently observed intraoperative symptom (Gras-Combe et al. 2012). There are two possible reasons for this discrepancy. First, differences in stimulation intensity (a weak stimulation, 2–4 mA) might account for differences in the symptoms observed by DES. Interestingly, two different symptoms (hallucination and phosphenes) were observed at the same point by changing the stimulus intensity in the same patient (Case No. 8), which strongly supports the notion that stimulus intensity levels can differentially influence intraoperative provoked symptoms. The second possible reason could be the differences in stimulated locations. In our patients, hallucinations were observed at the anterior temporal lobe during subcortical mapping, consistent with the cortical mapping study by Penfield (Penfield and Rasmussen 1950). The hallucinations were described as dream-like “flickering fancies,” and occurred when the DESs activated the temporal lobe cortex and evoked an experience memory. Additionally, they also addressed phosphenes elicited at the posterior temporal and occipital lobes, the symptoms of which included the perception of colors upon stimulation of the calcarine sulcus. These findings are similar to those observed in the subcortical mapping in our study. Thus, evoked symptoms may differ and may indicate differences (including the presence or absence of color perception) in visual cognitive functions, depending on the stimulation site, regardless of whether the site is in a cortical or subcortical region.
VBM analysis of the anatomic relationship between the stimulation site and optic radiation revealed that most of the positive intraoperative subcortical mapping were obtained near or on the optic radiation. Thus, the three aforementioned visual symptoms are the stimulation symptoms to the optic radiation itself. The results also suggest that other white matter networks, which were reported to be associated with visual-related processing (Herbet et al. 2018), such as the inferior longitudinal bundle, inferior fronto-occipital bundle, and vertical occipital bundle, were not the subcortical pathways responsible for the three visual symptoms.
The Visual Field and Quality of Life
Visual field deficit is a commonly observed postoperative complication after glioma surgery, particularly in cases where lesions are located in the temporal and occipital lobes. Inferior quadrantanopia is often symptomatic and results in a reduced QOL, although less than that due to hemianopsia. Hemianopsia significantly affects QOL, particularly, the ability to drive a vehicle. In European directives for driving licenses, which state the minimum visual standards for driving safely in Europe, the visual acuity standard is at least binocular vision of 20/40 and a visual field extending to 120° in the horizontal meridian (Bron et al. 2010). These criteria differ between countries; for example, Japanese driving licenses require both, a monocular vision greater than 20/28 feet and a visual field extending to 150° in the horizontal meridian. Driving a vehicle is an important life skill that allows individuals to maintain their independence and mobility; therefore, an attempt to prevent the exacerbation of vision disorders, at least to limit to a quadrantanopia, could lead to improvements in QOL. Furthermore, in a previous study that examined the relationship between intracranial disease and visual field abnormalities, it was revealed that all patients who were aware of their visual field abnormality had a visual defect in the central 5° field area by the Goldmann perimeter test (Horibe et al. 2005). Thus, prevention of visual defects in the central visual field could also help maintain a high QOL.
Postoperative visual outcomes are given much attention when surgical procedures are performed for brain tumors near the visual pathway. To date, several intraoperative techniques and modalities to prevent postoperative loss of the visual field have been attempted, and an awake craniotomy is one of the most efficient techniques to maintain the visual field. As early as the 1950s, Penfield first evaluated cortical visual function using DES (Penfield and Rasmussen 1950). After more than half a century, Duffau et al. reported the usefulness of direct electrophysiological detection of the optic radiation. This was the first report describing awake craniotomy for low-grade glioma to identify and preserve optic radiation in subcortical areas of the temporal lobe and temporo-occipital junction (Duffau et al. 2004). During the surgery, neurosurgeons terminated tumor resection when the patient experienced a visual field disturbance as an impression of “shadows” in the contralateral hemifield. Postoperatively, the patient presented with a mild visual disorder in the form of left and upper quadrantanopia. The same group subsequently proposed an intraoperative four-screen picture-naming test consisting of two objects situated diagonally on a screen divided into four quadrants (Gras-Combe et al. 2012). They performed awake resection in 14 cases of glioma (1 WHO Grade I, 11 WHO Grade II, 2 WHO Grade III) and was able to avoid postoperative homonymous hemianopsia in 13 of the 14 patients (93%), while 1 patient had no postoperative visual disorder (7%). In our study, using the same intraoperative task, we successfully prevented homonymous hemianopsia in all patients except for patients with occipital lesions (86%), and four patients exhibited no new visual field deficits after surgery (29%). The main factors contributing to more patients with postoperative hemiparesis in the present report than in previous reports (Gras-Combe et al. 2012) could have been the inclusion of lesions in the occipital lobe and the inclusion of more high-grade tumor cases. In the patients with temporal lesions, the postoperative visual field was asymptomatic or improved in 72% of the patients, and there were no patients with permanent hemianopsia. Meanwhile, two out of three patients with occipital lobe lesions suffered from hemianopsia without improvement of the visual field defect even in the postoperative chronic period. These findings indicate that intraoperative electrophysiological monitoring of the optic radiation is feasible but with limitations in preserving the functional integrity of the posterior optic radiation near the visual cortex in the occipital lobe. Moreover, our results suggest that intraoperative mapping of the visual field with the four-screen picture-naming test is an effective method for preventing postoperative visual defects, especially in patients with temporal lesions.
Recovery of Postoperative Visual Field
Although the mechanisms underlying the recovery of the visual field is not well understood, neuronal reorganization is considered to be one of the factors. From their extensive research on vision and plasticity, Hubel and Wiesel (1963) reported that neurons in the primary visual cortex of the kitten became unresponsive after elimination of visual input to the eye because of poor synapse formation from the lateral geniculate body to the visual cortex (Hubel and Wiesel 1963). Since then, increased attention has been given to visual cortex reorganization, particularly in peripheral vision disorders (Berardi et al. 2003; Maya-Vetencourt and Pizzorusso 2013; Papanikolaou et al. 2014). Regarding stroke, there are a few reports about visual functional reorganization in infants but with an unexpected absence of visual field deficits (Bova et al. 2008; Guzzetta et al. 2013). However, postoperative functional recovery in language, motor, and attentional networks after surgical resection of brain tumors has been reported (Charras et al. 2015; Shinoura et al. 2006). Duffau et al. reported that functional plasticity led to reorganization within 3 months after surgical resection of low-grade gliomas (Duffau et al. 2003). In the current study, reorganization is considered to be a mechanism for the postoperative improvements in visual field deficits because of the following three reasons. First, postoperative MRI assessments indicated that postoperative visual disorders were not caused by postoperative cerebral ischemia (data not shown). There are several reports of recovery of visual field deficits associated with cerebral infarction; the involvement of a resumption of blood flow via collateral circulation is considered to be one possible mechanism underlying this recovery (And and Kolmel 1991; Çelebisoy et al. 2011). Second, visual field defects were too prolonged to be caused by transient postoperative events, although immediate postoperative visual field deficits are typically associated with transient parenchymal edema or temporary damage of the area adjacent to the resection region. Our study indicated that the time necessary for visual neuronal circuits to reorganize for improvement in visual deficits is at least 6 months; this time period is similar to that reported in previous studies describing other neuronal symptoms (Jiao et al. 2020). Third, recent research suggested that neuronal synaptic plasticity could be activated by direct brain stimulation using repetitive transcranial magnetic stimulation for not only motor and language functions (Hartwigsen and Volz 2021) but also the visual system with large-scale brain network dynamics (Sabel et al. 2020). In neuronal synaptic microenvironments, electrical stimulation (Toni et al. 1999) and glutamate release (Kwon and Sabatini 2011) induce rapid structural changes (within minutes) and stabilization of stimulated dendritic spines, resulting in with long-term synaptic plasticity (Yuste and Bonhoeffer 2001). In our surgical procedure, frequent invasive DESs were applied adjacent to vision-related cortico-subcortical regions to identify the reproducible functions. However, the last hypothesis requires solid evidence from future basic and clinical studies.
Our study suggested that there was a poor prognostic factor, occipital lesion. In the present study, two out of three patients (66%) with occipital lesions continued exhibiting permanent hemianopsia. In a previous report, it was suggested that subcortical stimulation could identify the passage of the optic radiation when distances between the tip of the stimulating probe and the optic radiation were less than 10 mm, and that a proximate distance may lead to an increased risk of postoperative visual field deficits (Shahar et al. 2018). Therefore, postoperative visual disorder is more likely to occur in occipital lobe lesions with a short distance from the brain surface to the visual pathway. In this study, as in previous reports, the distance from the sites of symptom induction to the optic radiation was within 10 mm, but there was no significant difference in the relationship between the distance and presence of postoperative visual field symptoms. Furthermore, contrary to previous reports (Shahar et al. 2018), there was no correlation between postoperative visual impairment and stimulus intensity in our study, which could be because we used lower stimulus amplitudes of 2–6 mA compared to the 2–15 mA stimulus amplitudes used in previous studies.