Direct Evidence of Plasticity within Human Primary Motor and Somatosensory Cortices of Patients with Glioblastoma

Neural Plasticity ◽

10.1155/2020/8893708 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

William R. Gibb ◽

Nathan W. Kong ◽

Matthew C. Tate

Keyword(s):

Glioblastoma Multiforme ◽

Direct Evidence ◽

Standard Of Care ◽

Extent Of Resection ◽

Brain Regions ◽

Primary Brain Tumor ◽

Indirect Measures ◽

Somatosensory Cortices ◽

New Finding ◽

Subcortical Regions

Glioblastoma multiforme (GBM) is a devastating disease without cure. It is also the most common primary brain tumor in adults. Although aggressive surgical resection is standard of care, these operations are limited by tumor infiltration of critical cortical and subcortical regions. A better understanding of how the brain can recover and reorganize function in response to GBM would provide valuable clinical data. This ability, termed neuroplasticity, is not well understood in the adult human brain. A better understanding of neuroplasticity in GBM could allow for improved extent of resection, even in areas classically thought to have critical, static function. The best evidence to date has demonstrated neuroplasticity only in slower growing tumors or through indirect measures such as functional MRI or transcranial magnetic stimulation. In this novel study, we utilize a unique experimental paradigm to show direct evidence of plasticity via serial direct electrocortical stimulation (DES) within primary motor (M1) and somatosensory (S1) cortices in GBM patients. Six patients with glioblastoma multiforme in or near the primary motor or somatosensory cortex were included in this retrospective observational study. These patients had two awake craniotomies with DES to map cortical motor and sensory sites in M1 and S1. Five of six patients exhibited at least one site of neuroplasticity within M1 or S1. Out of the 51 total sites stimulated, 32 (62.7%) demonstrated plasticity. Of these sites, 14 (43.7%) were in M1 and 18 (56.3%) were in S1. These data suggest that even in patients with GBM in or near primary brain regions, significant functional reorganization is possible. This is a new finding which may lead to a better understanding of the fundamental factors promoting or inhibiting plasticity. Further exploration may aid in treatment of patients with brain tumors and other neurologic disorders.

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20 Disparities in survival for patients with glioblastoma multiforme

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2018.262 ◽

2018 ◽

Vol 45 (S3) ◽

pp. S4-S4

Author(s):

Mostafa Fatehi ◽

Camille Hunt ◽

Roy Ma ◽

Brian Toyota

Keyword(s):

British Columbia ◽

Overall Survival ◽

Glioblastoma Multiforme ◽

Median Overall Survival ◽

Performance Status ◽

Treatment Strategies ◽

Standard Of Care ◽

Extent Of Resection ◽

Pathologic Classification ◽

Genetic Features

Background: Glioblastoma multiforme (GBM) is the most common malignant primary brain cancer in adults. Recent efforts have elucidated genetic features of tumor cells and thus enhanced our knowledge of GBM pathophysiology. The most recent clinical trials report median overall survival between 14 and 20 months. However, real-world outcomes are quite variable and there is a paucity of data within the literature. Methods: Three hundred seventy two GBM patients were diagnosed in the province of British Columbia between January 2013 and January 2015. We have performed a retrospective review on the survival outcomes of the 278 patients who underwent surgical resection as part of the initial treatment. Results: Our results indicate a median age of 61.8y at time of diagnosis with a slight preponderance of males. The median overall survival was 10 months for patients who underwent surgery. As expected, patients over the age of 65 and those with worse initial Karnofsy Performance Status (KPS) scores had a poorer prognosis. Moreover, we have found extent of resection (EOR), treatment strategies and treatment location affect overall survival. Conclusion: The present study highlights factors which affect patient survival after surgery in British Columbia. Our outcomes are slightly worse than survival reported in the US. Variability in pathologic classification and in treatment strategy likely contribute to this difference. Further efforts should ensure access to the gold-standard of care.

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Reuse of Molecules for Glioblastoma Therapy

Pharmaceuticals ◽

10.3390/ph14020099 ◽

2021 ◽

Vol 14 (2) ◽

pp. 99

Author(s):

Abigail Koehler ◽

Aniruddha Karve ◽

Pankaj Desai ◽

Jack Arbiser ◽

David R. Plas ◽

...

Keyword(s):

Brain Tumor ◽

Glioblastoma Multiforme ◽

Standard Of Care ◽

Primary Brain Tumor ◽

Clinical Use ◽

Current Standard ◽

Non Invasive ◽

Tumor Treating Fields ◽

Emerging Treatments ◽

Stupp Protocol

Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor. The current standard of care for GBM is the Stupp protocol which includes surgical resection, followed by radiotherapy concomitant with the DNA alkylator temozolomide; however, survival under this treatment regimen is an abysmal 12–18 months. New and emerging treatments include the application of a physical device, non-invasive ‘tumor treating fields’ (TTFs), including its concomitant use with standard of care; and varied vaccines and immunotherapeutics being trialed. Some of these approaches have extended life by a few months over standard of care, but in some cases are only available for a minority of GBM patients. Extensive activity is also underway to repurpose and reposition therapeutics for GBM, either alone or in combination with the standard of care. In this review, we present select molecules that target different pathways and are at various stages of clinical translation as case studies to illustrate the rationale for their repurposing-repositioning and potential clinical use.

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Management of Glioblastoma Multiforme by Phytochemicals: Applications of Nanoparticle Based Targeted Drug Delivery System

Current Drug Targets ◽

10.2174/1389450121666200727115454 ◽

2020 ◽

Vol 21 ◽

Author(s):

Sayed Md Mumtaz ◽

Gautam Bhardwaj ◽

Shikha Goswami ◽

Rajiv Kumar Tonk ◽

Ramesh K. Goyal ◽

...

Keyword(s):

Drug Delivery ◽

Glioblastoma Multiforme ◽

Drug Delivery System ◽

Delivery System ◽

Genetic Disorder ◽

Drug Regimen ◽

Brain Regions ◽

Radio Therapy ◽

Novel Drug ◽

The Brain

: The Glioblastoma Multiforme (GBM; grade IV astrocytoma) exhort tumor of star-shaped glial cell in the brain. It is a fast-growing tumor that spreads to nearby brain regions specifically to cerebral hemispheres in frontal and temporal lobes. The etiology of GBM is unknown, but major risk factors are genetic disorder like neurofibromatosis and schwanomatosis which develop the tumor in the nervous system. The management of GBM with chemo-radio therapy leads to resistance and current drug regimen like Temozolomide (TMZ) is less efficacious. The reasons behind failure of drugs are due to DNA alkylation in cell cycle by enzyme DNA guanidase and mitochondrial dysfunction. Naturally occurring bio-active compounds from plants known as phytochemicals, serve as vital sources for anti-cancer drugs. Some typical examples include taxol analogs, vinca alkaloids such as vincristine, vinblastine, podophyllotoxin analogs, camptothecin, curcumin, aloe emodin, quercetin, berberine e.t.c. These phytochemicals often act via regulating molecular pathways which are implicated in growth and progression of cancers. However the challenges posed by the presence of BBB/BBTB to restrict passage of these phytochemicals, culminates in their low bioavailability and relative toxicity. In this review we integrated nanotech as novel drug delivery system to deliver phytochemicals from traditional medicine to the specific site within the brain for the management of GBM.

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Friend or Foe: Paradoxical Roles of Autophagy in Gliomagenesis

Cells ◽

10.3390/cells10061411 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1411

Author(s):

Don Carlo Ramos Batara ◽

Moon-Chang Choi ◽

Hyeon-Uk Shin ◽

Hyunggee Kim ◽

Sung-Hak Kim

Keyword(s):

Brain Tumor ◽

Glioblastoma Multiforme ◽

Cancer Biology ◽

Molecular Mechanisms ◽

Primary Brain Tumor ◽

Molecular Target ◽

Therapeutic Strategies ◽

Homeostatic Mechanism ◽

Cellular Context ◽

Cellular Components

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults, with a poor median survival of approximately 15 months after diagnosis. Despite several decades of intensive research on its cancer biology, treatment for GBM remains a challenge. Autophagy, a fundamental homeostatic mechanism, is responsible for degrading and recycling damaged or defective cellular components. It plays a paradoxical role in GBM by either promoting or suppressing tumor growth depending on the cellular context. A thorough understanding of autophagy’s pleiotropic roles is needed to develop potential therapeutic strategies for GBM. In this paper, we discussed molecular mechanisms and biphasic functions of autophagy in gliomagenesis. We also provided a summary of treatments for GBM, emphasizing the importance of autophagy as a promising molecular target for treating GBM.

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Phosphorous Magnetic Resonance Spectroscopy to Detect Regional Differences of Energy and Membrane Metabolism in Naïve Glioblastoma Multiforme

Cancers ◽

10.3390/cancers13112598 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2598

Author(s):

Lisa Maria Walchhofer ◽

Ruth Steiger ◽

Andreas Rietzler ◽

Johannes Kerschbaumer ◽

Christian Franz Freyschlag ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Healthy Volunteers ◽

Regional Differences ◽

Primary Brain Tumor ◽

Brain Parenchyma ◽

Resonance Spectroscopy ◽

31P Mrs ◽

Diffusion Parameters

Background: Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor with infiltration of, on conventional imaging, normal-appearing brain parenchyma. Phosphorus magnetic resonance spectroscopy (31P-MRS) enables the investigation of different energy and membrane metabolites. The aim of this study is to investigate regional differences of 31P-metabolites in GBM brains. Methods: In this study, we investigated 32 patients (13 female and 19 male; mean age 63 years) with naïve GBM using 31P-MRS and conventional MRI. Contrast-enhancing (CE), T2-hyperintense, adjacent and distant ipsilateral areas of the contralateral brain and the brains of age- and gender-matched healthy volunteers were assessed. Moreover, the 31P-MRS results were correlated with quantitative diffusion parameters. Results: Several metabolite ratios between the energy-dependent metabolites and/or the membrane metabolites differed significantly between the CE areas, the T2-hyperintense areas, the more distant areas, and even the brains of healthy volunteers. pH values and Mg2+ concentrations were highest in visible tumor areas and decreased with distance from them. These results are in accordance with the literature and correlated with quantitative diffusion parameters. Conclusions: This pilot study shows that 31P-MRS is feasible to show regional differences of energy and membrane metabolism in brains with naïve GBM, particularly between the different “normal-appearing” regions and between the contralateral hemisphere and healthy controls. Differences between various genetic mutations or clinical applicability for follow-up monitoring have to be assessed in a larger cohort.

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HIV Infection Is Associated with Attenuated Frontostriatal Intrinsic Connectivity: A Preliminary Study

Journal of the International Neuropsychological Society ◽

10.1017/s1355617715000156 ◽

2015 ◽

Vol 21 (3) ◽

pp. 203-213 ◽

Cited By ~ 39

Author(s):

Jonathan C. Ipser ◽

Gregory G. Brown ◽

Amanda Bischoff-Grethe ◽

Colm G. Connolly ◽

Ronald J. Ellis ◽

...

Keyword(s):

Hiv Infection ◽

Brain Regions ◽

Group Differences ◽

Hiv Rna ◽

Functional Connections ◽

Intrinsic Connectivity ◽

Dorsolateral Prefrontal ◽

Independent Replication ◽

Subcortical Regions ◽

The Brain

AbstractHIV-associated cognitive impairments are prevalent, and are consistent with injury to both frontal cortical and subcortical regions of the brain. The current study aimed to assess the association of HIV infection with functional connections within the frontostriatal network, circuitry hypothesized to be highly vulnerable to HIV infection. Fifteen HIV-positive and 15 demographically matched control participants underwent 6 min of resting-state functional magnetic resonance imaging (RS-fMRI). Multivariate group comparisons of age-adjusted estimates of connectivity within the frontostriatal network were derived from BOLD data for dorsolateral prefrontal cortex (DLPFC), dorsal caudate and mediodorsal thalamic regions of interest. Whole-brain comparisons of group differences in frontostriatal connectivity were conducted, as were pairwise tests of connectivity associations with measures of global cognitive functioning and clinical and immunological characteristics (nadir and current CD4 count, duration of HIV infection, plasma HIV RNA). HIV – associated reductions in connectivity were observed between the DLPFC and the dorsal caudate, particularly in younger participants (<50 years, N=9). Seropositive participants also demonstrated reductions in dorsal caudate connectivity to frontal and parietal brain regions previously demonstrated to be functionally connected to the DLPFC. Cognitive impairment, but none of the assessed clinical/immunological variables, was also associated with reduced frontostriatal connectivity. In conclusion, our data indicate that HIV is associated with attenuated intrinsic frontostriatal connectivity. Intrinsic connectivity of this network may therefore serve as a marker of the deleterious effects of HIV infection on the brain, possibly via HIV-associated dopaminergic abnormalities. These findings warrant independent replication in larger studies. (JINS, 2015, 21, 1–11)

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Glioblastoma Multiforme—A Look at the Past and a Glance at the Future

Pharmaceutics ◽

10.3390/pharmaceutics13071053 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1053

Author(s):

Jasmine L. King ◽

Soumya Rahima Benhabbour

Keyword(s):

Glioblastoma Multiforme ◽

Immune Surveillance ◽

Standard Of Care ◽

Current Standard ◽

Comprehensive Overview ◽

Therapeutic Delivery ◽

The Past ◽

Adults And Children ◽

The Central Nervous System ◽

Delivery Strategies

Gliomas are the most common type of brain tumor that occur in adults and children. Glioblastoma multiforme (GBM) is the most common, aggressive form of brain cancer in adults and is universally fatal. The current standard-of-care options for GBM include surgical resection, radiotherapy, and concomitant and/or adjuvant chemotherapy. One of the major challenges that impedes success of chemotherapy is the presence of the blood–brain barrier (BBB). Because of the tightly regulated BBB, immune surveillance in the central nervous system (CNS) is poor, contributing to unregulated glioma cell growth. This review gives a comprehensive overview of the latest advances in treatment of GBM with emphasis on the significant advances in immunotherapy and novel therapeutic delivery strategies to enhance treatment for GBM.

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On the cutting edge of glioblastoma surgery: where neurosurgeons agree and disagree on surgical decisions

Journal of Neurosurgery ◽

10.3171/2020.11.jns202897 ◽

2021 ◽

pp. 1-11

Author(s):

Domenique M. J. Müller ◽

Pierre A. Robe ◽

Hilko Ardon ◽

Frederik Barkhof ◽

Lorenzo Bello ◽

...

Keyword(s):

Decision Making ◽

Extent Of Resection ◽

Brain Regions ◽

Tumor Location ◽

Patient Treatment ◽

Study Cohort ◽

Surgical Decision ◽

Probability Maps ◽

The Right ◽

Surgical Decision Making

OBJECTIVE The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity. Standards are lacking for surgical decision-making, and previous studies indicate treatment variations. These shortcomings reflect the need to evaluate larger populations from different care teams. In this study, the authors used probability maps to quantify and compare surgical decision-making throughout the brain by 12 neurosurgical teams for patients with glioblastoma. METHODS The study included all adult patients who underwent first-time glioblastoma surgery in 2012–2013 and were treated by 1 of the 12 participating neurosurgical teams. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to identify and compare patient treatment variations. Brain regions with different biopsy and resection results between teams were identified and analyzed for patient functional outcome and survival. RESULTS The study cohort consisted of 1087 patients, of whom 363 underwent a biopsy and 724 a resection. Biopsy and resection decisions were generally comparable between teams, providing benchmarks for probability maps of resections and biopsies for glioblastoma. Differences in biopsy rates were identified for the right superior frontal gyrus and indicated variation in biopsy decisions. Differences in resection rates were identified for the left superior parietal lobule, indicating variations in resection decisions. CONCLUSIONS Probability maps of glioblastoma surgery enabled capture of clinical practice decisions and indicated that teams generally agreed on which region to biopsy or to resect. However, treatment variations reflecting clinical dilemmas were observed and pinpointed by using the probability maps, which could therefore be useful for quality-of-care discussions between surgical teams for patients with glioblastoma.

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Lesion Network Localization of Seizure Freedom following MR-guided Laser Interstitial Thermal Ablation

Scientific Reports ◽

10.1038/s41598-019-55015-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Karim Mithani ◽

Alexandre Boutet ◽

Jurgen Germann ◽

Gavin J. B. Elias ◽

Alexander G. Weil ◽

...

Keyword(s):

Resting State ◽

Target Selection ◽

Brain Regions ◽

Seizure Outcome ◽

Seizure Freedom ◽

Anatomical Location ◽

Treatment Resistant ◽

Resting State Functional Connectivity ◽

Network Localization ◽

Subcortical Regions

AbstractTreatment-resistant epilepsy is a common and debilitating neurological condition, for which neurosurgical cure is possible. Despite undergoing nearly identical ablation procedures however, individuals with treatment-resistant epilepsy frequently exhibit heterogeneous outcomes. We hypothesized that treatment response may be related to the brain regions to which MR-guided laser ablation volumes are functionally connected. To test this, we mapped the resting-state functional connectivity of surgical ablations that either resulted in seizure freedom (N = 11) or did not result in seizure freedom (N = 16) in over 1,000 normative connectomes. There was no difference seizure outcome with respect to the anatomical location of the ablations, and very little overlap between ablation areas was identified using the Dice Index. Ablations that did not result in seizure-freedom were preferentially connected to a number of cortical and subcortical regions, as well as multiple canonical resting-state networks. In contrast, ablations that led to seizure-freedom were more functionally connected to prefrontal cortices. Here, we demonstrate that underlying normative neural circuitry may in part explain heterogenous outcomes following ablation procedures in different brain regions. These findings may ultimately inform target selection for ablative epilepsy surgery based on normative intrinsic connectivity of the targeted volume.

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