Left Hemisphere Tumors Research Articles

Mapping nouns and finite verbs in left hemisphere tumors: a direct electrical stimulation study

ABSTRACTNeurosurgical mapping studies with nouns and finite verbs are scarce and subcortical data are nonexistent. We used a new task that uses finite verbs in six Italian-speaking patients with gliomas in the left language-dominant hemisphere. Language-relevant positive areas were detected only with nouns in four patients, with both tasks yet in distinct cortical areas in one patient, and only with finite verbs in another patient. Positive areas and types of errors varied across participants. Finite verbs provide complementary information to nouns, and permit more accurate mapping of language production when nouns are unaffected by electrical stimulation.

Language in individuals with left hemisphere tumors: Is spontaneous speech analysis equally good as formal testing?

Language in individuals with left hemisphere tumors: Is spontaneous speech analysis equally good as formal testing?

Dynamics of functional MRI and speech function in patients after resection of frontal and temporal lobe tumors

There are no studies on application of functional MRI (fMRI) for long-term monitoring of the condition of patients after resection of frontal and temporal lobe tumors. The study purpose was to correlate, using fMRI, reorganization of the speech system and dynamics of speech disorders in patients with left hemisphere gliomas before surgery and in the early and late postoperative periods. A total of 20 patients with left hemisphere gliomas were dynamically monitored using fMRI and comprehensive neuropsychological testing. The tumor was located in the frontal lobe in 12 patients and in the temporal lobe in 8 patients. Fifteen patients underwent primary surgery; 5 patients had repeated surgery. Sixteen patients had WHO Grade II and Grade III gliomas; the others had WHO Grade IV gliomas. Nineteen patients were examined preoperatively; 20 patients were examined at different times after surgery. Speech functions were assessed by a Luria's test; the dominant hand was determined using the Annette questionnaire; a family history of left-handedness was investigated. Functional MRI was performed on an HDtx 3.0 T scanner using BrainWavePA 2.0, Z software for fMRI data processing program for all calculations >7, p<0.001. In patients with extensive tumors and recurrent tumors, activation of right-sided homologues of the speech areas cold be detected even before surgery; but in most patients, the activation was detected 3 months or more after surgery. Therefore, reorganization of the speech system took time. Activation of right-sided homologues of the speech areas remained in all patients for up to a year. Simultaneous activation of right-sided homologues of both speech areas, the Broca's and Wernicke's areas, was detected more often in patients with frontal lobe tumors than in those with temporal lobe tumors. No additional activation foci in the left hemisphere were found at the thresholds used to process fMRI data. Recovery of the speech function, to a certain degree, occurred in all patients, but no clear correlation with fMRI data was found. Complex fMRI and neuropsychological studies in 20 patients after resection of frontal and temporal lobe tumors revealed individual features of speech system reorganization within one year follow-up. Probably, activation of right-sided homologues of the speech areas in the presence of left hemisphere tumors depends not only on the severity of speech disorder but also reflects individual involvement of the right hemisphere in enabling speech function. This is confirmed by right-sided activation, according to the fMRI data, in right-sided patients without aphasia and, conversely, the lack of activation of right-sided homologues of the speech areas in several patients with severe postoperative speech disorders during the entire follow-up period.

Variability of intraoperative electrostimulation parameters in conscious individuals: language cortex.

OBJECTIVE Electrostimulation in awake brain mapping is widely used to guide tumor removal, but methodologies can differ substantially across institutions. The authors studied electrostimulation brain mapping data to characterize the variability of the current intensity threshold across patients and the effect of its variations on the number, type, and surface area of the essential language areas detected. METHODS Over 7 years, the authors prospectively studied 100 adult patients who were undergoing intraoperative brain mapping during resection of left hemisphere tumors. In all 100 cases, the same protocol of electrostimulation brain mapping (a controlled naming task-bipolar stimulation with biphasic square wave pulses of 1-msec duration and 60-Hz trains, maximum train duration 6 sec) and electrocorticography was used to detect essential language areas. RESULTS The minimum positive thresholds of stimulation varied from patient to patient; the mean minimum intensity required to detect interference was 4.46 mA (range 1.5-9 mA), and in a substantial proportion of sites (13.5%) interference was detected only at intensities above 6 mA. The threshold varied within a given patient for different naming areas in 22% of cases. Stimulation of the same naming area with greater intensities led to slight changes in the type of response in 19% of cases and different types of responses in 4.5%. Naming sites detected were located in subcentimeter cortical areas (50% were less than 20 mm2), but their extent varied with the intensity of stimulation. During a brain mapping session, the same intensity of stimulation reproduced the same type of interference in 94% of the cases. There was no statistically significant difference between the mean stimulation intensities required to produce interfereince in the left inferior frontal lobe (Broca's area), the supramarginal gyri, and the posterior temporal region. CONCLUSIONS Intrasubject and intersubject variations of the minimum thresholds of positive naming areas and changes in the type of response and in the size of these areas according to the intensity used may limit the interpretation of data from electrostimulation in awake brain mapping. To optimize the identification of language areas during electrostimulation brain mapping, it is important to use different intensities of stimulation at the maximum possible currents, avoiding afterdischarges. This could refine the clinical results and scientific data derived from these mapping sessions.

Infiltration of the basal ganglia by brain tumors is associated with the development of co-dominant language function on fMRI

Studies have shown that some patients with left-hemispheric brain tumors have an increased propensity for developing right-sided language support. However, the precise trigger for establishing co-dominant language function in brain tumor patients remains unknown. We analyzed the MR scans of patients with left-hemispheric tumors and either co-dominant (n=35) or left-hemisphere dominant (n=35) language function on fMRI to investigate anatomical factors influencing hemispheric language dominance. Of eleven neuroanatomical areas evaluated for tumor involvement, the basal ganglia was significantly correlated with co-dominant language function (p<0.001). Moreover, among patients whose tumors invaded the basal ganglia, those with language co-dominance performed significantly better on the Boston Naming Test, a clinical measure of aphasia, compared to their left-lateralized counterparts (56.5 versus 36.5, p=0.025). While further studies are needed to elucidate the role of the basal ganglia in establishing co-dominance, our results suggest that reactive co-dominance may afford a behavioral advantage to patients with left-hemispheric tumors.

Post-Surgical Language Reorganization Occurs in Tumors of the Dominant and Non-Dominant Hemisphere.

Surgical resection of brain tumors may shift the location of cortical language areas. Studies of language reorganization primarily investigated left-hemispheric tumors irrespective of hemispheric language dominance. We used functional magnetic resonance imaging (fMRI) to investigate how tumors influence post-surgical language reorganization in relation to the dominant language areas. A total of, 17 patients with brain tumors (16 gliomas, one metastasis) in the frontotemporal and lower parietal lobes planned for awake surgery underwent pre-surgical and post-surgical language fMRI. Language activation post-to-pre surgery was evaluated visually and quantitatively on the statistically thresholded images on patient-by-patient basis. Results were qualitatively compared between three patient groups: temporal, with tumors in the dominant temporal lobe, frontal, with tumors in the dominant frontal lobe and remote, with tumors in the non-dominant hemisphere. Post-to-pre-surgical distributions of activated voxels changed in all except the one patient with metastasis. Changes were more pronounced in the dominant hemisphere for all three groups, showing increased number of activated voxels and also new activation areas. Tumor resection in the dominant hemisphere (frontal and temporal) shifted the activation from frontal towards temporal, whereas tumor resection in the non-dominant hemisphere shifted the activation from temporal towards frontal dominant areas. Resection of gliomas in the dominant and in the non-dominant hemisphere induces postsurgical shifts and increase in language activation, indicating that infiltrating gliomas have a widespread influence on the language network. The dominant hemisphere gained most of the language activation irrespective of tumor localization, possibly reflecting recovery of pre-surgical tumor-induced suppression of these activations.

Othello syndrome in a patient with two left hemispheric tumors

We report a case of a patient with Othello syndrome caused by two left hemispheric tumors. This 50-year-old female had experienced seizures for 10 years and developed manic-like symptoms, delusions of jealousy, persecution and being watched, auditory hallucinations, irritable mood, and violent and disorganized behavior for the past 3 years. Brain imaging studies revealed two left frontal tumors, the larger of which was causing a mass effect. The delusions of jealousy in Othello syndrome resolved after removing the larger tumor, and the other psychiatric symptoms improved after treatment with psychotropic medications. This report aims to raise awareness of Othello syndrome related to disruptions in cortico-subcortical connections in the left orbitofrontal region. Timely surgical treatment may prevent associated psychiatric comorbidities and increase the likelihood of a good outcome.

Neurocognitive effects of proton radiation therapy in adults with low-grade glioma.

To understand neurocognitive effects of proton radiation therapy (PRT) in patients with low-grade glioma, we evaluated 20 patients who received this therapy prospectively and over 5 years with a comprehensive neuropsychological battery. 20 patients were evaluated at baseline and at yearly intervals for up to 5 years with a battery of neuropsychological measures that assessed intellectual, attention, executive, visuospatial and memory functions as well as mood and functional status. We evaluated change in cognitive functioning over time. We analyzed the relationship between cognitive performance and tumor location and also examined whether patients' performance differed from that reported in a study of normative practice effects. Overall, patients exhibited stability in cognitive functioning. Tumor location played a role in performance; those with tumors in the left hemisphere versus in the right hemisphere were more impaired at baseline on verbal measures (p < .05). However, we found greater improvement in verbal memory over time in patients with left than with right hemisphere tumors (p < .05). Results of our study, the first to investigate, in depth, neurocognitive effects of PRT in adults with low-grade gliomas, are promising. We hypothesize that the conformal advantage of PRT may contribute to preservation of cognitive functioning, although larger sample sizes and a longer period of study are required. Our study also highlights the need to consider normative practice effects when studying neurocognitive functioning in response to treatment over time, and the need to utilize comprehensive neuropsychological batteries given our findings that differentiate patients with left and right hemisphere tumors.

Predictors of subjective versus objective cognitive functioning in patients with stable grades II and III glioma.

Studies in cancer and noncancer populations demonstrate lower than expected correlations between subjective cognitive symptoms and cognitive functioning as determined by standardized neuropsychological tests. This paper systematically examines the association between subjective and objective cognitive functioning in patients with low-grade glioma and the associations of these indicators of cognitive function with clusters of sociodemographic, clinical, and self-reported physical and mental health factors. Multiple regression analyses with the subjective and 2 objective indicators of cognitive functioning as dependent variables and 4 clusters of predictor variables were conducted in 169 patients with predominantly low-grade glioma. Correlations between the subjective and the 2 objective cognitive indicators were negligible (0.04) to low (0.24). Objective cognitive deficits were predominantly associated with sociodemographic (older age, lower education, male sex) and clinical (left hemisphere tumor) variables, while lower ratings of subjective cognitive function were more closely related to self-reported mental health symptoms (fatigue, lower mental well-being), physical (motor) dysfunction and female sex. Self-reported communication deficits were associated significantly with both subjective and objective dysfunction. We recommend that both subjective and objective measures of cognitive functioning, together with a measure of psychological distress, be used for comprehensive neuropsychological assessments of patients with glioma to determine which areas are most affected and which specific intervention strategies are most appropriate.

Crossed-brain representation of verbal and nonverbal functions.

A 74-year-old, left-handed man presented with a rapidly evolving loss of strength in his right leg associated with difficulty in walking. MR images disclosed an extensive left hemisphere tumor. A neuropsychological examination revealed that language was broadly normal but that the patient presented with severe nonlinguistic abnormalities, including hemineglect (both somatic and spatial), constructional defects, and general spatial disturbances; symptoms were usually associated with right hemisphere pathologies. No ideomotor apraxia was found. The implications of crossed-brain representations of verbal and nonverbal functions are analyzed.

NT-25 * EARLY JAPANESE EXPERIENCE WITH NovoTTF-100A SYSTEM FOR RECURRENT GBM

BACKGROUND: NovoTTF-100A System is an FDA-approved treatment for recurrent glioblastoma (GBM) and is defined as a device of high unmet medical need in Japan. Subsequently, the device has been made available on a restricted case basis for compassionate use in Japan. Here we report initial experience with 10 patients treated at Tokyo Women's Medical University, Kashiwaba Neurosurgical Hospital and Japanese Red Cross Medical Center. METHODS: Using retrospective chart review, we analyzed patient demographics, tumor size, location, and treatment compliance with NovoTTF-100A System from the device log files. Duration of therapy was estimated using the Kaplan-Meier estimate. Adverse event frequency and severity was also evaluated. RESULTS: Ten (10) patients with supra-tentorial recurrent GBM were treated between July 8, 2013 and June 3, 2014 at 3 Japanese hospitals. 80% were male and 20% female. The median age was 41 years (range 32-66). The average baseline tumor burden was 13.3 cm2. 40% of patients had bi-hemispheric tumors and 30% left hemispheric tumors. The K-M median duration of therapy was 7.8 months. Average daily device compliance was 17.4 hours. This is consistent with prior global studies which have demonstrated average daily device compliance of 70-80%. The device was well-tolerated with no reported serious adverse events. The only device-related adverse events were mild skin irritation. CONCLUSIONS: NovoTTF-100A System was safe and well-tolerated in an initial cohort of Japanese patients with GBM. Device usage and compliance was consistent with that observed in non-Japanese patients.

Tumour and surgery effects on cognitive functioning in high-grade glioma patients.

Many high-grade glioma (HGG) patients have cognitive impairments, which impact daily functioning. Cognitive impairments can be caused by tumour-, treatment-, and patient-related factors. The effect of the tumour and of surgical resection on cognition is, however, not well known. We investigated tumour and surgical effects on cognitive functioning in patients with HGG. At baseline, preceding surgery, 62 patients with HGG underwent neuropsychological testing concerning seven cognitive domains: verbal and working memory, attention, executive functioning, psychomotor function, information processing speed, and visuoconstructive abilities. Thirty-nine patients were included in follow-up testing after surgery, but before subsequent treatment. Tumour size and site, use of anti-epileptic drugs and corticosteroids, and extent of resection were recorded. Compared to healthy controls, cognitive functioning of patients was significantly impaired in all domains. Prior to surgery 79 % (49 of 62) of patients had cognitive impairment in at least one domain. At median follow-up of 5 weeks after surgery, 59 % (23 of 39) of patients were cognitively impaired in at least one domain. At follow-up, 49 % showed improvement, while 23 % declined. Left hemisphere tumour localization was associated with worse verbal memory (P=0.004), and larger tumours in this hemisphere with poorer executive functioning (P < 0.001). Changes in cognitive performance at follow-up relative to baseline were not related to tumour characteristics or extent of resection. Tumour-related cognitive deficits are present in a majority of HGG patients preceding surgery. Surgery does not result in cognitive deterioration in the short term in most patients.

Is the usage of mannitol mandatory in awake craniotomy? A comparative study

ObjectivesAssessment of the value of using mannitol for the reduction of intracranial pressure and optimizing surgical condition during awake craniotomy.MethodsForty patients; 21 males and 19 females; 21 ASA I and 19 ASA II patients. Twenty patients had left hemispheric tumors and 14 patients had right hemispheric tumors, while six patients suffered from epilepsy. Patients were randomly allocated into two equal groups. Group A, was given mannitol, while to group B no mannitol was given (but kept as a rescue drug). Intracranial pressure (ICP) and blood gases were recorded every 15 min till the end of surgery. Surgeon satisfaction regarding brain status, tense or slack was recorded. Postoperative nausea and vomiting (PONV), fits and electrolyte disturbances were noted.ResultsIntracranial pressure (ICP) readings were comparable between the two groups at baseline, skin incision and 15 min after. Mannitol effect on ICP appeared as a lower reading of ICP in group A from 30 min after skin incision till dural exposure and incision. Impact of hyperventilation on ICP measures was evident in both groups since prior to dural incision till after dural closure. However, there was no difference regarding brain status judged by the surgeon between the two groups as brain was found to be slack in 19 patients versus18 patients in groups A and B, respectively. Blood CO2 levels in blood gases showed progressive declination in both groups from the start of hyperventilation till the end of surgery. Potassium (K+) correction was needed in four patients in the mannitol group. Three patients in group A suffered from nausea versus one patient in group B. A single patient in each group suffered from fits.ConclusionUsage of mannitol did not add much benefit over ICP perception and brain status in elective awake craniotomy and mannitol should be kept as a rescue drug if needed.

46 An integrative structural and functional approach to pancreatic cancer gene discovery

Studies have shown that some patients with left-hemispheric brain tumors have an increased propensity for developing right-sided language support. However, the precise trigger for establishing co-dominant language function in brain tumor patients remains unknown. We analyzed the MR scans of patients with left-hemispheric tumors and either co-dominant (n = 35) or left-hemisphere dominant (n = 35) language function on fMRI to investigate anatomical factors influencing hemispheric language dominance. Of eleven neuroanatomical areas evaluated for tumor involvement, the basal ganglia was significantly correlated with co-dominant language function (p < 0.001). Moreover, among patients whose tumors invaded the basal ganglia, those with language co-dominance performed significantly better on the Boston Naming Test, a clinical measure of aphasia, compared to their left-lateralized counterparts (56.5 versus 36.5, p = 0.025). While further studies are needed to elucidate the role of the basal ganglia in establishing co-dominance, our results suggest that reactive co-dominance may afford a behavioral advantage to patients with left-hemispheric tumors.

Aphasia in patients after brain tumour resection

Background: It is has been estimated that aphasia occurs in one‐third to half of patients who have had a left hemisphere brain tumour resection. While studies have documented aphasia before malignant brain tumour resection, little is known about the type and severity of aphasia after tumour resection. Aims: The aims of this study were (1) to describe the subtypes and severity of aphasia during the acute recovery period after malignant brain tumour resection; (2) to describe potential associations between acute language outcomes and tumour characteristics; and (3) to compare our findings to those reported in the literature to identify possible language differences between patients who suffer stroke and patients who undergo brain tumour resection. Methods & Procedures: We retrospectively reviewed the Western Aphasia Battery (WAB) scores during the acute recovery period of individuals who underwent resection of malignant brain tumours to determine patterns of aphasia severity and subtype. Outcomes & Results: We found that aphasia was usually mild (63% of patients) and that anomic aphasia was the most common subtype (48% of patients) during the acute recovery period after brain tumour resection, regardless of lesion location or tumour grade. Conclusions: The patterns of postoperative language functioning that we observed during the acute recovery period after surgery for a brain tumour support the perspective that acute aphasia profiles may be fundamentally different in patients with brain tumours compared with patients who have had a stroke.

Comparison of Time–Frequency Responses and the Event-Related Potential to Auditory Speech Stimuli in Human Cortex

We recorded the electrocorticogram directly from the exposed cortical surface of awake neurosurgical patients during the presentation of auditory syllable stimuli. All patients were unanesthetized as part of a language-mapping procedure for subsequent left-hemisphere tumor resection. Time-frequency analyses showed significant high-gamma (gammahigh: 70-160 Hz) responses from the left superior temporal gyrus, but no reliable response from the left inferior frontal gyrus. Alpha suppression (alpha: 7-14 Hz) and event-related potential responses exhibited a more widespread topography. Across electrodes, the alpha suppression from 200 to 450 ms correlated with the preceding (50-200 ms) gammahigh increase. The results are discussed in terms of the different physiological origins of these electrocortical signals.

Quality of life in low-grade glioma patients receiving temozolomide

The purpose of this study was to describe the quality of life (QOL) of low-grade glioma (LGG) patients at baseline prior to chemotherapy and through 12 cycles of temozolomide (TMZ) chemotherapy. Patients with histologically confirmed LGG with only prior surgery were given TMZ for 12 cycles. QOL assessments by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) were obtained at baseline prior to chemotherapy and at 2-month intervals while receiving TMZ. Patients with LGG at baseline prior to chemotherapy had higher reported social well-being scores (mean difference = 5.0; p < 0.01) but had lower reported emotional well-being scores (mean difference = 2.2; p < 0.01) compared to a normal population. Compared to patients with left hemisphere tumors, patients with right hemisphere tumors reported higher physical well-being scores (p = 0.01): 44% could not drive, 26% did not feel independent, and 26% were afraid of having a seizure. Difficulty with work was noted in 24%. Mean change scores at each chemotherapy cycle compared to baseline for all QOL subscales showed either no significant change or were significantly positive (p < 0.01). Patients with LGG on TMZ at baseline prior to chemotherapy reported QOL comparable to a normal population with the exception of social and emotional well-being, and those with right hemisphere tumors reported higher physical well-being scores compared to those with left hemisphere tumors. While remaining on therapy, LGG patients were able to maintain their QOL in all realms. LGG patients' QOL may be further improved by addressing their emotional well-being and their loss of independence in terms of driving or working.

Cognitive and Adaptive Outcome in Extracerebellar Low-Grade Brain Tumors in Children: A Report From the Children's Oncology Group

To determine whether pediatric patients treated with surgery only for low-grade tumors in the cerebral hemispheres, supratentorial midline, and exophytic brainstem evidence neurocognitive, academic, adaptive, or emotional/behavioral sequelae. Ninety-three patients from a natural history study of low-grade astrocytomas were tested an average of 111 days after surgery. Rates of below average (< or = 25th percentile) scores in this sample were compared with test norms, and performances were compared across anatomic sites. Finally, the relationships of pre-, peri-, and postsurgical complications to outcome were investigated. For the entire sample, there was a significantly elevated rate of below average scores across intelligence quotient, achievement, and adaptive behavior, but not behavioral/emotional adjustment measures. Patients with hemispheric, midline, and brainstem tumors did not differ significantly. Patients with left hemisphere tumors generally performed worse than those with right hemisphere tumors. Finally, neurobehavioral outcome was unrelated to pre-, peri-, or postsurgery complications. After surgery for low-grade brain tumors, a significant number of patients was found to function below average, by as much as 55% compared with 25% in the normative population. Moreover, these results suggest greater risk for patients with lesions situated in the left cerebral hemisphere. Routine neuropsychological follow-up of children after treatment for low-grade tumors is recommended.

Suggestive Evidence for an Involvement of the Right Hemisphere in the Recovery from Childhood Aphasia: A 3-Year Follow-Up Case Study

We describe the case of an 11-year-old, previously healthy, pre-puberal, right-handed girl with acquired aphasia following an extensive cerebral hemorrhage into a left hemisphere brain tumor. A 3-year follow-up evaluation of the girl's communicative performance showed an incomplete recovery of linguistic abilities with a good recovery of comprehensive components, but persisting severe impairment in expressive language. At the end of the follow-up period, with the aim of assessing the lateralization of some linguistic abilities, we carried out an experimental investigation using tachistoscopic reading and object naming tests along with a dichotic listening test. All these tests showed a clear left field/left ear—right hemisphere advantage. We discuss both clinical and experimental results with regard to implications for the linguistic abilities of the right hemisphere in late versus early childhood and its interaction with aetiology in the recovery from acquired childhood aphasia. We wish to thank P. for her unwavering patience throughout testing, and M. Veronese for his help with preparing the experimental stimuli and the figures. The financial contribution of the Ministero dell'Istruzione, dell'Università e della Ricerca is also gratefully acknowledged.

From the left to the right: How the brain compensates progressive loss of language function

In normal right-handed subjects language production usually is a function oft the left brain hemisphere. Patients with aphasia following brain damage to the left hemisphere have a considerable potential to compensate for the loss of this function. Sometimes, but not always, areas of the right hemisphere which are homologous to language areas of the left hemisphere in normal subjects are successfully employed for compensation but this integration process may need time to develop. We investigated right-handed patients with left hemisphere brain tumors as a model of continuously progressive brain damage to left hemisphere language areas using functional neuroimaging and transcranial magnetic stimulation (TMS) to identify factors which determine successful compensation of lost language function. Only patients with slowly progressing brain lesions recovered right-sided language function as detected by TMS. In patients with rapidly progressive lesions no right-sided language function was found and language performance was linearly correlated with the lateralization of language related brain activation to the left hemisphere. It can thus be concluded that time is the factor which determines successful integration of the right hemisphere into the language network for compensation of lost left hemisphere language function.