Surgical treatment of frontal lobe glial tumors. Current state of the problem. Part III: clinical, neurophysiological and surgical nuances

Intra-operative subcortical electrical stimulation: A comparison of two methods

INTRODUCTION: Slowly growing deeply situated brain tumors in children pose a unique management dilemma. Considerations of watchful waiting, resection, chemotherapy and radiation therapy must be weighed carefully. With concerns over neurosurgical resection morbidity, the typical long-term ineffectiveness of chemotherapy and the feared sequelae of radiation therapy, our institution has chosen to manage select tumors using laser interstitial ablation via the stereotactic Visualase® system. METHODS: Five patients, ages 7, 8, 12, 15, 16 years had clinicoradiographic histories of slowly enlarging deep brain lesions characteristic of low-grade glial tumors. Locations included deep thalamus (2), cerebellar vermis (1), parieto-occiptal region (1) and a SEGA near a foramen of Monro (1). Options for management were discussed with each family, and laser ablation was decided upon. RESULTS: The patients were taken to the intraoperative MRI operating room for stereotactic needle biopsy and laser interstitial ablation during the same operation. Frozen section tissue analysis in all cases showed a low-grade glial tumor. Each patient underwent standard post-operative scanning, all showing evidence of lesional/peri-lesional signal change, a sign suggestive of desired zonal ablation injury to the tumor. Four patients had no evidence of post-procedure complications and were discharged several days post-procedure. One patient (cerebellar vermis) had significant post-ablation procedure ataxia and had evidence of incomplete ablation by virtue of tumor progression 16 months later, requiring a second ablation. None had evidence of concerning hemorrhage. All tumors were finalized as being low-grade glial (pilocytic) tumors. CONCLUSIONS: Stereotactic laser ablation therapy should be considered as an option in the management of select patients with deeply-situated glial tumors, in order to avoid potential serious neurosurgical morbidity via resection, or the dangers of irradiation. Continued long-term patient follow up will be needed in order to determine whether ablation therapy was successful. Further reporting on this technique by other investigators is suggested.

Oligodendrogliomas account for 5-20% of all glial tumors. They have a predilection for the frontal lobe and are commonly seen in adults (1). Oligodendrogliomas are rare in children and account for less than 1%-2% of primary pediatric brain tumors (2). Herein, we report a childhood oligodendroglioma that was misdiagnosed as meningioma and discuss diagnostic pitfalls of childhood oligodendrogliomas. A 4-year-old boy who had intractable generalized tonic-clonic seizures for two years was admitted to our hospital. A magnetic resonance imaging (MRI) scan of the brain showed an isointense lesion in the right frontotemporal region just over the anterior clinoid process reaching the right basal ganglia superiorly. T1weighted images (T1WI) showed a lesion with heterogeneous contrast enhancement (Figure 1). The lesion was hypointense in susceptibility weighted MRI (SWI) sequences and isointense in T1WI and T2WI (Figure 2). Computerized tomography (CT) revealed a hyperdense lesion located under the frontal lobe, which was interpreted in favor of coarse calcification (Figure 3). Digital subtraction angiography revealed angiogenesis under the right frontal lobe. We performed multivoxel magnetic resonance spectroscopy (MRS) with 135 ms and 30 ms echo time values and the findings were in accordance with a low grade glial tumor. The patient underwent a right frontotemporal craniotomy under general anesthesia. Postoperative period was uneventful and the patient’s neurological examination was unremarkable. Histopathologic examination of the specimen was consistent with oligodendroglioma grade II.

Inhibition of fatty acid synthase leads to apoptosis in cancers, which leads to high levels of fatty acid synthesis. This indicates that cancer cells depend on fatty acid in order to survive. In this study, we investigated whether or not there was a relationship between the glial tumor grade and free fatty acid level of tumor tissue. Twenty patients who had high grade glial tumors and 20 patients who had low grade glial tumors, were included in the study. Tumors samples were obtained intraoperatively in order to measure the fatty acid levels. The fatty acids were studied in three groups: saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids. They were analyzed with gas chromatography. The oleic acid, linoleic acid, eicosadienoic acid, arachidonic acid, and docosadienoic acid levels were high in the tumor tissue of low grade tumors. The myristic acid, palmitic acid, stearic acid, alpha linoleic acid, eicosenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, and ceramide levels were high in the tumor tissue of high grade glial tumors. However, none of these high values were statistically significant. The high values of behenic acid, a saturated fatty acid, in low grade glial tumors were statistically significant. High levels of behenic acid in patients with low grade glial tumor is important as it indicates persistence of the tissue integrity and tissue resistance. behenic acid levels can be a prognostic factor in glial tumors.

Dysembryoplastic neuroepithelial tumors (DNETs) are rare, generally benign, mixed neuronal-glial neoplasms occurring most often between 10 and 14 years of age. These lesions are classically cortically based and solitary, found preferentially in the temporal lobe, and most commonly present with seizures. On magnetic resonance imaging (MRI), these lesions are generally cystic and have variable contrast enhancement, which, when present, often involves the periphery. Rarely, lesions followed radiographically may demonstrate delayed contrast enhancement. Here, we present a case of multifocal DNETs involving the cerebellum that demonstrated delayed contrast enhancement. In addition, these occurred in a patient with Noonan syndrome (NS), a “RASopathy” disorder associated with low-grade glial and glioneuronal tumors. We present a summary of all previously reported cases of cerebellar DNETs. Our patient was successfully treated surgically and is doing well clinically, now one year status post his last procedure, and is being closely monitored with serial MRIs for progression. Gross total resection is often curative without adjuvant therapy for most DNETs. Our case emphasizes the importance of radiographic surveillance, as multifocality and recurrence may necessitate more than one procedure. Lastly, clinicians should be suspicious for DNETs and other low-grade glial tumors when treating patients with NS, acknowledging their predisposition for multifocal involvement and atypical presentations.

In everyday clinical practice, neurosurgeons usually deal with glial tumors localized precisely in the frontal lobe. There is a widespread opinion that almost any neurosurgeon can resect glioma of the frontal lobe regardless of experience and microsurgical skills. However, working at the federal center, we observe how employees often have to operate on patients with frontal lobe gliomas after previous surgery in other hospitals. Therefore, treatment of these patients seems to be quite difficult problem of neurosurgery for glial tumors, and incidence of postoperative complications is still high. We analyzed literature data on anatomical and functional aspects of surgery for frontal lobe gliomas and practical nuances of their surgical treatment. Motor functional system of the frontal lobe is represented by several cortical zones united into a complexly organized network of functional connections through associative fibers. Theor lesion can lead to postoperative motor deficit.

Many glioma patients struggle to return to work after surgery because of higher brain dysfunction. Although the right frontal lobe has historically been considered functionally silent, reports of performing awake surgery to evaluate higher brain functions in patients with tumors in this area have increased. We present two cases of patients who underwent awake surgery for malignant glioma in the right frontal lobe to preserve emotional recognition and facilitate an early return to work. Case 1 was a 48-year-old right-handed woman employed as a nursery school teacher and case 2 was a 21-year-old right-handed man employed in sales. Both had contrast-enhancing right frontal lobe tumors exhibiting high signal intensity on fluid attenuated inversion recovery imaging and underwent awake surgery. During the operation, cortical mapping was performed using the Reading the Mind in the Eyes, calculation, and motor tasks. Resection of sites involved in motor and emotional recognition functions was avoided. In case 1, all regions of high signal intensity were completely resected; in case 2, all regions exhibiting enhancement were resected. Both patients were discharged home without neurological deficits and returned to work within 21 days after surgery. It may be important to focus not only on overall survival and progression-free survival in glioma patients, but also on factors associated with life satisfaction, such as time to return to work after surgery and time until work becomes difficult. Awake surgery aimed at preserving higher brain functions is useful and may also improve life satisfaction.

Background Many glioma patients struggle to return to work after surgery because of higher brain dysfunction. Although the right frontal lobe has historically been considered functionally silent, reports of performing awake surgery to evaluate higher brain functions in patients with tumors in this area have increased. We present two patients who underwent awake surgery for malignant glioma in the right frontal lobe to preserve emotional recognition and facilitate an early return to work. Case Presentation: Case 1 was a 48-year-old right-handed woman employed as a nursery school teacher and case 2 was a 21-year-old right-handed man employed in sales. Both had contrast-enhancing right frontal lobe tumors exhibiting high signal intensity on fluid attenuated inversion recovery imaging and underwent awake surgery. During the operation, cortical mapping was performed using the Reading the Mind in the Eyes, calculation, and motor tasks. Resection of sites involved in motor and emotional recognition functions was avoided. In case 1, all regions of high signal intensity were completely resected; in case 2, all regions exhibiting enhancement were resected. Both patients were discharged home without neurological deficits and returned to work within 21 days after surgery. Conclusion It may be important to focus not only on overall survival and progression free survival in glioma patients, but also on factors associated with life satisfaction, such as time to return to work after surgery and time until work becomes difficult. Awake surgery aimed at preserving higher brain functions is useful and may also improve life satisfaction.

The purpose of this study was to evaluate the relationship between apparent diffusion coefficient (ADC) measured by MR imaging and the level of immunohistochemical expression of hyaluronan or hyaluronic acid as one of the main hydrophilic components of the extracellular matrix in brain glial tumors. Nineteen patients with primary glial brain tumors were included in the study. Mean ADC values were calculated in all tumors and were normalized with the ADC values of the contralateral normal-appearing brain ratios. All tumors underwent surgical resection, and the histologic diagnosis was based on the analysis of the surgical specimen. Mean values of the labeling index of hyaluronan (LI-HA) were calculated to determine quantifiably the histochemical expression of hyaluronan in the tumor. The mean ADC values and the mean ADC ratios (ADC(ratio)) of the tumors were then correlated to the mean values of the LI-HA. The mean ADC (93 x 10(-5) mm(2)/sec) and the mean ADC(ratio) (1.25) of the high-grade glial tumors were significantly lower than the mean ADC (123 x 10(-5) mm/sec) and the mean ADC(ratio) (1.64) of the low-grade glial tumors (p < 0.01). The mean LI-HA (72.8%) was also significantly lower in the high-grade gliomas than the mean LI-HA (93.4%) in the low-grade gliomas (p < 0.001). A positive correlation was found between mean ADC values and the mean LI-HA (tau = 0.35, p < 0.05) and also between the mean ADC(ratio) and the mean LI-HA (tau = 0.33, p < 0.05). Hyaluronan as one of the main hydrophilic components of the extracellular matrix in gliomas likely contributes to differences in the ADC values between high- and low-grade glial tumors.

Glial tumors are the most common primary neoplasms of the central nervous system. Their proportion in the total structure of primary brain tumors is 50-65%. In Ukraine, according to the statistical data of the cancer-registry of the year 2014, 49,3% of patients with primary diagnosed malignant neoplasms of the brain did not live for one year. The aim of the study was to improve the survival rates of patients with low-grade glial tumors (LGT) (grade III-IV) by determining optimal treatment strategy and main prognostic survival factors. A prospective study of the results of treatment of patients with LGT from 2009 to 2014 was conducted . The study consistently included 100 operated patients with LGT (anaplastic astrocytoma (AA) and glioblastoma (GLB)). The median survival in the total group of patients (n=100) was 363.5 days (12 months). The main statistically significant prognostic factors of survival were : the completeness of tumor removal (p=0.00000000007) and the character of adjuvant therapy (p=0.000012). With the removal of LGT III-IV grade aplasias , which do not spread to functionally important areas and deep areas of the brain, one should try to perform Gross-total resection (GTR), which ensures long-term survival. The median survival of patients after GTR was 22.3 months. An integrated approach to the treatment which includes surgery, adjuvant radiotherapy and monochemotherapy with temozolamide showed the best survival rates – 20.5 months.

The aims of this study are to analyze how the nature and the behavior of low-grade glial tumors (LGGT) in children may correlate with the anatomy of the cerebral hemispheres and to evaluate the consequent impact of diffusion tensor imaging (DTI) techniques in the presurgical assessment. This is a combined review of a series of 155 cases of LGGT and of the recent literature on the subject. The cases retrieved from our data bank were divided in central hemispheric tumors (basal ganglia and thalami) (36 cases), glioneuronal cortical-based tumors (49 cases), and glial tumors of the cerebral mantle (70 cases). A close correlation was found in the thalamus between the primary location of the tumor (juxta-ventricular, inferior, lateral, bilateral) and its extension (ventricular lumen, midbrain and mesial temporal, globus pallidus, respectively) which may relate to the connectivity. Among the glioneuronal tumors, most gangliogliomas were located in the temporal lobe and especially in the mesial temporal structures. In addition, the morphologic feature of the ganglioglioma was different there from the neocortical areas. As a complementary approach, DTI data may assist in evaluating the structure and the extension of the LGGT, in addition to planning the surgical strategy. In the cerebral hemispheres like in the rest of the central nervous system, there is some degree of correlation between the anatomy and the nature, appearance, and behavior of the LGGT in children.

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.

Treatment of Psychiatric Symptoms Associated With a Frontal Lobe Tumor Through Surgical Resection

BackgroundThe human brain is the most complex organ in the body, and it is important to have a better understanding of how the protein composition in the brain regions contributes to the pathogenesis of associated neurological disorders.MethodsIn this study, a comparative analysis of the frontal and temporal cortex proteomes was conducted by isobaric tags of relative and absolute quantification (iTRAQ) labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS). Brain protein was taken from relatively normal tissue that could not be avoided of damage during emergent surgery of the TBI (traumatic brain injury) patients admitted in Beijing Tiantan Hospital from 2014 to 2017. Eight cases were included. Four frontal lobes and 4 temporal lobes proteome were analyzed and the proteins were quantitated. Gene Ontology (GO), Ingenuity Pathway Analysis (IPA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze the biological function of identified proteins, unchanged proteins, and differentially expressed proteins (DEPs).ResultsA total number of 2127 protein groups were identified in the frontal and temporal lobe proteomes. A total of 1709 proteins could be quantitated in both the frontal and temporal cortex. Among 90 DEPs, 14 proteins were screened highly expressed in the temporal cortex, including MAPT, SNCG, ATP5IF1, GAP43, HSPE1, STMN1, NDUFS6, LDHB, SNCB, NDUFA7, MRPS36, EPDR1, CISD1, and RALA. In addition, compared to proteins expressed in the frontal cortex, 14 proteins including EDC4, NIT2, VWF, ASTN1, TGM2, SSB, CLU, HBA1, STOM, CRP, LRG1, SAA2, S100A4, and VTN were a low expression in the temporal cortex. The biological process enrichment showed that unchanged proteins between the frontal and temporal cortex mainly take part in regulated exocytosis, axon guidance, and vesicle-mediated transport. The KEGG pathway analysis showed that unchanged proteins between the frontal and temporal cortex mainly take part in oxidative phosphorylation, carbon metabolism, Huntington’s disease, and Parkinson’s disease.ConclusionsThe majority of proteins are unchanged between the frontal and temporal cortex, and unchanged proteins are closely related to its function. Among DEPs, MATP (tau) is upregulated in the temporal cortex, closely related to Alzheimer’s disease (AD), and is one of the targets for the treatment of AD. CLU is downregulated in the temporal cortex which functions as an extracellular chaperone that prevents aggregation of non-native proteins. It was suggested that the temporal lobe may not be the “functional dumb area” of the traditional view, but could be involved in important neural metabolic circuits.

Lipid peroxidation in cerebral tumors