An "epileptic scent": Olfactory auras in tumor-related epilepsy.

OBJECTIVES: To characterize a profile for patients with tumor-related epilepsy presenting olfactory auras. MATERIALS AND METHODS: We conducted a monocentric, retrospective study on patients who underwent surgery in the Neurosurgery Unit of Udine University Hospital (Udine, Italy), between the 1st of January 2010 and the 1st of January 2019, for primary brain tumors (PBTs) involving the temporal lobe and the insula. All patients were affected by tumor-related epilepsy; the study group presented olfactory auras as well. We collected neuroradiological, neuropsychological and neurophysiological data from patients' medical charts. RESULTS: The subtraction analysis of MRI data shows maximum lesion overlay in left olfactory cortex, left and right hippocampus, left amygdala, right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus. The presence of olfactory auras did not influence seizure outcome (p = 0.500) or tumor recurrence after surgery (p = 0.185). The type of auras (elementary vs. complex), also, did not influence seizure control (p = 0.222). DISCUSSION: In presence of olfactory auras, anterior and mesial temporal regions are mainly involved, such as olfactory cortex, amygdala, and anterior hippocampus, together with right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus, suggesting their possible role in the genesis of olfactory auras. Post-surgical seizure outcome and disease relapse are not influenced by neither the presence nor the type of olfactory auras. CONCLUSIONS: Olfactory auras are rare event, however they may be often underestimated by the patients and under-investigated by the clinicians, even when their occurrence can represent a useful localizing tool.

Cognitive reserve and individual differences in brain tumour patients.

The aim of the paper is to determine the effects of the cognitive reserve on brain tumour patients' cognitive functions and, specifically, if cognitive reserve helps patients cope with the negative effects of brain tumours on their cognitive functions. We retrospectively studied a large sample of around 700 patients, diagnosed with a brain tumour. Each received an MRI brain examination and performed a battery of tests measuring their cognitive abilities before they underwent neurosurgery. To account for the complexity of cognitive reserve, we construct our cognitive reserve proxy by combining three predictors of patients' cognitive performance, namely, patients' education, occupation, and the environment where they live. Our statistical analysis controls for the type, side, site, and size of the lesion, for fluid intelligence quotient, and for age and gender, in order to tease out the effect of cognitive reserve on each of these tests. Clinical neurological variables have the expected effects on cognitive functions. We find a robust positive effect of cognitive reserve on patients' cognitive performance. Moreover, we find that cognitive reserve modulates the effects of the volume of the lesion: the additional negative impact of an increase in the tumour size on patients' performance is less severe for patients with higher cognitive reserve. We also find substantial differences in these effects depending on the cerebral hemisphere where the lesion occurred and on the cognitive function considered. For several of these functions, the positive effect of cognitive reserve is stronger for patients with lesions in the left hemisphere than for patients whose lesions are in the right hemisphere. The development of prevention strategies and personalized rehabilitation interventions will benefit from our contribution to understanding the role of cognitive reserve, in addition to that of neurological variables, as one of the factors determining the patients' individual differences in cognitive performance caused by brain tumours.

Continuous Real-Time Neuropsychological Testing during Resection Phase in Left and Right Prefrontal Brain Tumors.

BACKGROUND: Executive functions are multi-component and are based on large-scale brain networks. For patients undergoing brain surgery in the prefrontal cortex, resection in the anterior prefrontal sites is assisted by continuous monitoring of their performance on several tasks measuring components of executive functions. In this study, we did not test patients during direct cortical stimulation, but during resection itself. We chose tests routinely used to assess executive functions and included them in a protocol for left (LH) and right (RH) hemisphere prefrontal resections. This protocol is meant to be used during real-time neuropsychological testing (RTNT)-an already established monitoring technique. METHODS: We retrospectively reviewed a consecutive series of 29 adult patients with glioma in the superior and middle frontal areas who performed the RTNT sequence throughout the resection phase. The testing protocol comprised 10 tests for LH frontal resections and 9 tests for RH frontal resections. RESULTS: RH patients showed a median performance on RTNT with significantly lower scores for visuo-spatial attention and emotion processing (95% Confidence Interval Lower bound of 66.55 and 82.57, respectively, χ2 (7) = 32.8, p < 0.001). LH patients showed a median performance on RTNT, with significantly lower scores for selective attention and working memory (95% Confidence Interval Lower bound of 51.12, χ2 (5) = 20.31 p < 0.001) and minimum scores for the same task and for the Stroop test (χ2 (5) = 17.86, p < 0.005). The delta for accuracy between the first and the last RTNT run was not statistically significant (RH patients: χ2 (7) = 10.49, p > 0.05, n.s.; LH patients: χ2 (5) = 3.35, p > 0.05, n.s.). Mean extent of resection was 95.33% ± 9.72 for the RH group and 94.64% ± 6.74 for the LH group. Patients showed good performance post- vs. pre-surgery. The greater difference in the number of LH patients scoring within the normal range was found for the symbol-digit modality test (83.3% to 62%), Stroop test (100% to 77%) and short-term memory (84.61% to 72.72%) and working memory (92.3% to 63.63%). For RH patients, the main changes were observed on the clock drawing test (100% to 77.7%) and cognitive estimation (100% to 72.7%). CONCLUSIONS: Frontal RTNT offers continuous and reliable feedback on the patients' cognitive status during resection in frontal areas.

Incidental low grade glioma in young female: An indolent lesion? A case report and a literature review.

OBJECTIVE: The wide use of brain MRI has led to an increased diagnosis of incidental low-grade gliomas (LGGs). There is no consensus regarding the surgical treatment of incidental LGGs, nor even when we deal with a young woman who wants to plan a pregnancy. We performed a literature review on the topic of cognitive testing and pregnancy in LGGs. Results on the patients' cognitive status are poorly addressed: if, after surgery, neuropsychological deficits were to arise, this would greatly complicate the management of a child by a mother who is an oncological patient, and, moreover, has developed cognitive alterations that may compromise the abilities to look after a baby. We also report the case of a 30-years old woman with a diagnosis of incidental LGG who underwent a first surgery for a right-frontal oligodendroglioma METHODS: The patient underwent two awake surgeries and in both performed the Real Time Neuropsychological Testing (RTNT). We acquired clinical and MRI data. This paper also reports a literature review on the topic of cognitive testing and pregnancy in LGGs highlighting a lack of adequate data about this issue. RESULTS: No deterioration of neuropsychological performances was documented during surgery. During the follow-up, she became pregnant and, despite an increased growth rate of the lesion, she did not accuse any symptom or sign of evolution in high-grade glioma (HGG). She underwent a second awake surgery with RTNT. Performance was maintained within the normal range. CONCLUSIONS: We concluded that, in our experience, pregnancy could induce an increased growth rate of LGG, not influencing the prognosis.

Performing real time neuropsychological testing during awake craniotomy: are dexmedetomidine or propofol the same? A preliminary report.

PURPOSE: In awake surgery, the patient is sedated, but is also required to be sufficiently alert and collaborative during extensive neurocognitive testing. In the present preliminary report of a retrospective single-center study, a continuous series of 168 patients who underwent awake surgery for brain tumor located near eloquent areas, was investigated to observe the effect of dexmedetomidine (n = 58) compared with propofol (n = 110) on vigilance and collaboration required to perform extensive intra-operatory Real Time Neuropsychological Testing (RTNT). METHODS: We assigned a score to each patient, by using a scale that combines vigilance and collaboration in a 5 levels score (the higher score denoting higher level). RESULTS: The median interquartile range was significantly lower (range 3-5) for the dexmedetomidine group compared to the propofol one (range 4-5, p = .044). Patients with intra-operative seizures (p = .014) and/or electrocorticographic slow/epileptiform activity (p = .042), and patients in the propofol group who showed increased heart rate (p = .032) were those who obtained the lower scores (lower vigilance and collaboration level). CONCLUSION: The study shows that the effect of dexmedetomidine or propofol -based conscious sedation on ability to perform Real Time Neuropsychological Testing during awake surgery for supratentorial tumor resection is different. Although both permit high mean levels of vigilance and collaboration, the patient who received dexmedetomidine was more likely to show lower vigilance and collaboration during RTNT.

Real-Time Neuropsychological Testing of Sensorimotor Cognition During Awake Surgery in Precentral and Postsomatosensory Areas.

BACKGROUND: For patients undergoing brain surgery, once primary motor and sensory areas are identified by direct electrical stimulation, resection can be performed in the precentral and postsomatosensory areas while monitoring cognition. For this purpose, we developed a real-time neuropsychological testing (RTNT) protocol tapping sensorimotor cognition. METHODS: We retrospectively reviewed a consecutive series of 57 adult patients with tumors in the precentral and postsomatosensory areas who performed the RTNT sequence. The testing protocol used continuously throughout resection for excisions comprised action verbs, mental rotation of body parts, action imagery, action semantics, ideomotor praxis, and short-term memory. RESULTS: The patients' median performance on RTNT tests was significantly lower for mental rotation and action imagery (χ2 (2) = 55.98, P < 0.001), as well as their minimum value of patients' performance (χ2 (2) = 85.048, P < 0.001) and their delta calculated between the patients' performance at the first versus the last RTNT run (χ2 (2) = 14.33, P < 0.05). Patients showing such decreases in performance on action imagery had lesions overlapping on the right precentral and postcentral gyrus, the supplementary motor area, and the superior and inferior parietal lobe. For the mental rotation task, their maximum lesion overlay included the right cingulum/supplementary motor area and left superior and inferior parietal lobe and medial precuneus. The mean resection extent was 91.15% ± 17.45 and correlated with the number of motor-related positive sites found by the direct electrical stimulation at cortical (r = -0.279, P = 0.020) and white matter (r = -0.417, P = 0.001) level. CONCLUSIONS: The sensory-motor RTNT is performed to assist surgery in the precentral and postsomatosensory areas.

Presurgical cognitive status in patients with low-grade glioma and epilepsy: Testing the effects of seizures, antiseizure medications, and tumor localization.

BACKGROUND: Low-grade gliomas (LGGs) are frequently associated with epilepsy. There are few studies addressing the impact of seizures, antiseizure medications (ASMs), and lesion localization on presurgery cognitive functioning. METHODS: We tested the relation between the above-mentioned variables in a continuous series of 73 young patients (mean age 38.3 years ± 11.7) affected by LGGs and epilepsy. The anatomical areas, involved in this sample, were the left insula with surrounding cortical and subcortical areas, the right precentral gyrus/rolandic operculum, and the white matter and cortical regions beneath. RESULTS: Patients' presurgery cognitive status was within the normal range, with borderline performance for some tasks. We tested whether lower scores were related with lesion or with epilepsy-related factors. Multiple regression identified variables that predict test scores. The Token test score was predicted by a model (p = .0078) containing the DT2T1 MRI, corrected for seizure features. Object naming performance was predicted by a model (p = .0113) containing the localization, the DT2T1 MRI, corrected for sex, EEG, and onset. Verbal fluency score was predicted by a model (p = .0056) containing the localization and the DT2T1 MRI, corrected for AEDs and EEG. Working memory score was predicted by a model (p = .0117) containing Engel class, the DT2T1 MRI, corrected for sex. Clock drawing score was predicted by a model (p < .0001) containing the Engel class, AEDs, and EEG. TMT A score was predicted by a model (p = .0022) containing localization, corrected for EEG. TMT B-A score was predicted by a model (p = .0373) containing localization. Voxel Lesion Symptom Mapping analyses carried out on patients' lesion volumes confirmed that patients' level of performance correlated with lesion-related variables. CONCLUSION: This preliminary study indicates that the presurgical level of performance for language tasks and for cognitive flexibility and shifting is mainly predicted by lesion-related variables, working memory by both lesion and epilepsy-related variables. Epilepsy clinical and instrumental characteristics predicted performance for visuospatial planning.

Real-Time Neuropsychological Testing Protocol for Left Temporal Brain Tumor Surgery: A Technical Note and Case Report.

Background: The risk of surgery in eloquent areas is related to neuropsychological dysfunctions. Maximizing the extent of resection increases the overall survival. The onco-functional balance is mandatory when surgery involves cognitive areas, and maximal information on the cognitive status of patients during awake surgery is needed. This can be achieved using direct cortical stimulation mapping and, in addition to this, a neuropsychological monitoring technique called real-time neuropsychological testing (RTNT). The RTNT includes testing protocols based on the area where the surgery is performed. We reported on tests used for left temporal lobe surgery and our RTNT decision tree. Case Report: We reported our RTNT experience with a 25-year-old right-handed man with 13 years of schooling. He reported daily partial seizures. MRI revealed the presence of a low-grade glioma involving the temporo-insular cortex. The neuropsychological status presurgery which was within the normal range was combined with functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) information. Awake surgery plus RTNT was performed. Direct electrical stimulation during object naming elicited a motor speech arrest. Resection was continuously accompanied by the RTNT. The RTNT provided enriched information to the surgeon. Performance never dropped. A slight decrement in accuracy emerged for pseudoword repetition, short-term memory and working memory, phonological processing, and verbal comprehension. Total resection was performed, and the histological examination confirmed the nature of the lesion. Immediate postsurgery performance was within the normal range as it was the fMRI and DTI assessment. Conclusion: The RTNT provides essential information that can be used online, during surgery, for clinical aims to provide the surgeon with useful feedback on the cognitive status of patients.

Pre-Surgery Cognitive Performance and Voxel-Based Lesion-Symptom Mapping in Patients with Left High-Grade Glioma.

(1) Background: The literature on the effects of high-grade glioma (HGG) growth on cognition is still scarce. (2) Method: A consecutive series of 85 patients with HGG involving the left hemisphere underwent an extended neuropsychological evaluation prior to surgery. Voxel-based lesion-symptom mapping (VLSM) was used to identify regions related to cognitive performance. (3) Results: The patients' mean level of pre-surgery accuracy was overall high. They showed the greatest difficulties in language with tasks such as naming (42.1% of patients impaired on nouns and 61.4% on verbs), reading (36.3% on words and 32.7% on pseudo-words), auditory lexical decisions (43.9%) and writing (41.3%) being most frequently impaired. VLSM analysis revealed anatomically separated areas along the temporal cortex and the white matter related to impairments on the different tasks, with voxels commonly shared by all tasks restricted to a small region in the ventral superior and middle temporal gyrus. (4) Conclusions: High-grade glioma affects cognition; nonetheless, lesions do not cause diffuse deficits but selectively impact the different language sub-domains along the ventral stream and the dorsal stream for language processing.

Risk Assessment by Pre-surgical Tractography in Left Hemisphere Low-Grade Gliomas.

Background: Tracking the white matter principal tracts is routinely typically included during the pre-surgery planning examinations and has revealed to limit functional resection of low-grade gliomas (LGGs) in eloquent areas. Objective: We examined the integrity of the Superior Longitudinal Fasciculus (SLF) and Inferior Fronto-Occipital Fasciculus (IFOF), both known to be part of the language-related network in patients with LGGs involving the temporo-insular cortex. In a comparative approach, we contrasted the main quantitative fiber tracking values in the tumoral (T) and healthy (H) hemispheres to test whether or not this ratio could discriminate amongst patients with different post-operative outcomes. Methods: Twenty-six patients with LGGs were included. We obtained quantitative fiber tracking values in the tumoral and healthy hemispheres and calculated the ratio (HIFOF-TIFOF)/HIFOF and the ratio (HSLF-TSLF)/HSLF on the number of streamlines. We analyzed how these values varied between patients with and without post-operative neurological outcomes and between patients with different post-operative Engel classes. Results: The ratio for both IFOF and SLF significantly differed between patient with and without post-operative neurological language deficits. No associations were found between white matter structural changes and post-operative seizure outcomes. Conclusions: Calculating the ratio on the number of streamlines and fractional anisotropy between the tumoral and the healthy hemispheres resulted to be a useful approach, which can prove to be useful during the pre-operative planning examination, as it gives a glimpse on the potential clinical outcomes in patients with LGGs involving the left temporo-insular cortex.

What's behind drawing for an artist with left temporal lobe epilepsy? A multimodal neurophysiological study.

There are few studies in literature reporting drawing as a strong trigger of praxis-induced focal seizures. The aim of the present case report was describing a case of focal epilepsy with praxis induced EEG activation, due to a cavernoma, in the left middle anterior temporal lobe by using a multimodal approach. We combined video-EEG, showing that drawing increased a sustained monomorphic delta activity localized on left anterior temporal region (F7-T1a), diffusing to the vertex (Fz) and the fronto-polar electrodes (F3), with DTI data, showing that the left uncinate fasciculus, connecting the temporal pole to the orbitofrontal cortex, significantly differed from controls. fMRI confirmed that drawing increased activation in these areas. The congruence between findings supports the role of the left uncinated fasciculus linking the temporal lobe to the orbitofrontal cortex in the present focal epilepsy mainly facilitated by drawing.

Cognitive Functions in Repeated Glioma Surgery.

Low-grade gliomas (LGG) are slow-growing brain tumors infiltrating the central nervous system which tend to recur, often with malignant degeneration after primary treatment. Re-operations are not always recommended due to an assumed higher risk of neurological and cognitive deficits. However, this assumption is relatively ungrounded due to a lack of extensive neuropsychological testing. We retrospectively examined a series of 40 patients with recurrent glioma in eloquent areas of the left hemisphere, who all completed comprehensive pre- (T3) and post-surgical (T4) neuropsychological assessments after a second surgery (4-month follow up). The lesions were most frequent in the left insular cortex and the inferior frontal gyrus. Among this series, in 17 patients the cognitive outcomes were compared before the first surgery (T1), 4 months after the first surgery (T2), and at T3 and T4. There was no significant difference either in the number of patients scoring within the normal range between T3 and T4, or in their level of performance. Further addressing the T1-T4 evolution, there was no significant difference in the number of patients scoring within the normal range. As to their level of performance, the only significant change was in phonological fluency. This longitudinal follow-up study showed that repeated glioma surgery is possible without major damage to cognitive functions in the short-term period (4 months) after surgery.

Junior-Real Time neuropsychological testing (j-RTNT) for a young patient undergoing awake craniotomy.

We developed a junior-real-time neuropsychological testing (j-RTNT) and used it during surgery of a right fronto-insular dysembryoplastic neuroepithelial tumor causing seizures in a 16 years old female. The j-RTNT included tasks from the battery NEPSY-II. Pre-surgery evaluation detected a below average performance in visuo-spatial planning, inhibition, visual attention, planning and borderline performance in speeded naming. The j-RTNT allows detecting sudden decreases that could be caused by resection. During surgery, ECoG was characterized by slow sharp activity and spikes on the electrodes exploring the right fronto-polar region. After the resection, spikes were not detected anymore. Immediate post-surgery performance resulted within the normal range, remained below average in visuo-spatial planning, and improved in inhibition, switching and in speeded naming. Follow-up revealed cognitive recovery. Neurological assessment was unremarkable and the patient was seizure free. No epileptic activity could be observed on follow-up EEG. fMRI data showed that in the follow-up vs. pre-surgery there was a higher recruitment of the right superior frontal gyrus, a region involved in the cognitive execution and cognitive control networks. The j-RTNT is feasible with young patients, goes beyond the testing of limited functions, assessing multiple times during resection several different functions to better monitoring the effects of resection.

Multimodal Assessment Shows a Mostly Preserved Cognitive Status in Incidentally Discovered Low Grade Gliomas: A Single Institution Study.

Incidentally discovered low-grade gliomas (iLGGs) are poorly reported in the literature. Still less is known about iLGG patients' neuropsychological profile: It is unclear whether iLGG patients are cognitively proficient, thus further confirming the concept of asymptomatic. From our monoinstitutional cohort of 332 patients operated for LGG from 2000 to 2017 we selected those who underwent a neuropsychological testing (n = 217, from 2008 to 2017), and identified 24 young (mean age 38.5 ± 1.06) patients with iLGGs (16 of 24, left hemisphere iLGGs, 8 of 24 right hemisphere iLGGs). The maximum lesions overlap occurred in the left inferior frontal gyrus and in the right anterior cingulate/superior medial frontal gyrus. Patients were cognitively preserved except mild to borderline difficulties in a few of them. The analysis of the equivalent scores (a score laying below or equal to the external nonparametric tolerance limit of adjusted scores corresponding to 0, 1, 2 and 3 are intermediate) highlighted the presence of additional borderline performances. Molecular class correlated with a normal function at visual-spatial intelligence (p = 0.05) and at spatial short-term memory (p = 0.029). Results indicate that at this time of tumor growth, patients' cognitive abilities are still functional, but are slowly approaching the borderline level.

Meningioma can lead to pre-operative cognitive alterations even if localized in sensorimotor areas: A multimodal MRI-neuropsychological study in a series of 46 patients.

Brain tumors are generally associated with cognitive changes. Little is known about cognition in patients with meningioma - a lesion that usually shifts and compresses the brain parenchyma with a low probability of infiltrate it. We investigated the cognitive functioning in a consecutive series of 46 patients with a meningioma in the sensorimotor area in the left (LH, N = 27) or in the right (RH, N = 19) hemisphere. All the patients underwent a pre-operative neuropsychological assessment and structural MRI. Clinical symptoms varied between LH and RH meningioma patients. Impaired performance was seen in naming (19.23% noun and 35% verb naming), short-term (18.18%) and working (14.24%) memory in the LH group, and in visuo-spatial tasks (25% neglect, 21.42% visuospatial planning) in the RH group. Both groups were impaired on a sensorimotor mental imagery task (LH, 66.66% of the LH 70% of the RH meningioma patients), while only the RH meningioma group was impaired on the visuo-spatial mental imagery task. The lesion MRI maximum overlap occurred in the postcentral and paracentral lobules. Edema was maximally localized on the left superior longitudinal fasciculus and the superior part of the right superior corona radiata. We found that only the meningioma mass, and not the edema, is a predictive variable in determining patients' performance. Patients with meningioma could present with cognitive alterations at pre-surgical evaluation even if the meningioma occurs in sensorimotor areas. In the present series, a large meningioma vs. a large edema is more relevant for cognitive performance.