Glioma is a broad term that refers to a diverse group of brain tumors that arise from glial cells—the supportive and insulating cells that surround and protect neurons in the central nervous system (CNS). These tumors account for about 30% of all brain and CNS tumors and roughly 80% of all malignant brain tumors. Gliomas vary significantly in their behavior, ranging from slow-growing benign lesions to aggressive cancers such as glioblastoma, which is one of the most lethal forms of brain cancer. 

Despite major advancements in diagnosis and treatment, gliomas remain challenging due to their resistance to conventional therapies and their ability to infiltrate surrounding brain tissue. With molecular and genetic discoveries transforming how gliomas are classified and treated, researchers continue to seek new strategies to improve survival and quality of life. This article explores glioma in depth—from causes and symptoms to treatment and future directions. 

Gliomas are primary brain tumors that originate from glial cells, including astrocytes, oligodendrocytes, and ependymal cells. The World Health Organization (WHO) classifies gliomas by both histological type and grade, ranging from Grade I (least aggressive) to Grade IV (most aggressive). These grades reflect tumor growth rate, invasiveness, and cellular abnormalities. 

Major Types of Gliomas 

• Astrocytomas (including glioblastoma) 

• Oligodendrogliomas 

• Ependymomas 

• Mixed gliomas (rare) 

WHO Grading System 

• Grade I: Pilocytic astrocytoma (slow-growing, often in children) 

• Grade II: Low-grade astrocytoma or oligodendroglioma (infiltrative, slower progression) 

• Grade III: Anaplastic astrocytoma or oligodendroglioma (malignant) 

• Grade IV: Glioblastoma (highly aggressive, poor prognosis) 

The updated 2021 WHO classification integrates molecular markers such as IDH mutations and 1p/19q codeletion into glioma diagnoses, improving accuracy and treatment guidance. 

Gliomas can occur at any age, though they are more frequent in adults and increase with age. Glioblastoma, the most common and aggressive glioma, peaks between ages 55 and 75. 

Key facts: 

• Incidence: Approximately 5 per 100,000 people annually 

• Sex: Slightly more common in men than women (ratio 1.3:1) 

• Geography: Higher rates in North America and Europe than in Asia or Africa 

• Risk factors include: 
  • Exposure to ionizing radiation 
  • Inherited genetic syndromes (Li-Fraumeni, Neurofibromatosis type 1) 
  • Rare familial glioma history 

No consistent evidence supports links between gliomas and cell phone use, diet, or most environmental exposures. 

The precise cause of glioma remains unclear, but scientists recognize a combination of genetic, environmental, and molecular factors. 

Genetic Factors 

• Inherited syndromes such as Li-Fraumeni, Turcot, and Neurofibromatosis (NF1/NF2) 

• Gene mutations including TP53, EGFR amplification, and PTEN loss 

Environmental Factors 

• Ionizing radiation (such as therapeutic cranial radiation) 

• Possible but unconfirmed risks from electromagnetic fields or certain chemicals 

Molecular and Genetic Markers 

• IDH1/IDH2 mutations: Found in low-grade gliomas, associated with better outcomes 

• 1p/19q codeletion: Common in oligodendrogliomas, predicts good response to therapy 

• MGMT promoter methylation: Predicts sensitivity to temozolomide (chemotherapy) 

• TERT promoter and EGFR amplification: Seen in aggressive glioblastomas 

Gliomas arise when normal glial cells undergo genetic mutations that alter their growth, division, and survival. Over time, these cells gain the ability to invade nearby tissues and resist cell death. 

Key Mechanisms 

• Initiating mutations (e.g., IDH mutations) 

• Cell cycle disruption (loss of TP53, CDKN2A) 

• Growth factor pathway activation (EGFR, PDGFR) 

• Angiogenesis (formation of new blood vessels driven by VEGF) 

• Infiltration through white matter tracts and extracellular matrix degradation 

High-grade gliomas, especially glioblastoma, show aggressive features such as necrosis and abnormal microvascular proliferation. These traits make surgical removal difficult and contribute to recurrence. 

Glioma symptoms depend on the tumor’s size, location, and rate of growth. Some develop slowly, while others progress rapidly. 

Common symptoms include: 

• Persistent or worsening headaches (often worse in the morning) 

• Seizures, especially in low-grade gliomas 

• Focal neurological deficits such as: 
  • Weakness or paralysis on one side (hemiparesis) 
  • Speech difficulties (aphasia) 
  • Vision loss or double vision 

• Personality or cognitive changes 

• Nausea and vomiting due to increased intracranial pressure 

• Balance or coordination problems (ataxia) 

High-grade gliomas often cause rapid symptom progression, while low-grade forms may present subtly over months or years. 

Diagnosing glioma involves a combination of imaging, pathology, and molecular testing. 

Imaging 

Magnetic Resonance Imaging (MRI) with contrast is the gold standard. 

• T1-weighted: Hypo- or isointense lesion 

• T2/FLAIR: Hyperintense signal 

• Contrast enhancement: High-grade gliomas often have ring-enhancing lesions 

• Advanced MRI techniques (perfusion, spectroscopy) help determine tumor grade and treatment response. 

CT scans can detect calcifications or hemorrhage but are less detailed than MRI. 

Biopsy and Molecular Testing 

A biopsy or surgical specimen is required for definitive diagnosis. Pathology confirms tumor type and grade, while genetic testing identifies key molecular features (IDH mutation, 1p/19q codeletion, MGMT methylation) critical for prognosis and therapy planning. 

Because gliomas share features with several other brain lesions, differential diagnosis may include: 

• Metastatic brain tumors 

• Primary CNS lymphoma 

• Brain abscess 

• Demyelinating disease (e.g., tumefactive multiple sclerosis) 

• Subacute infarction 

• Meningioma or medulloblastoma 

The treatment approach depends on tumor type, grade, molecular profile, and patient factors such as age and neurological status. A multidisciplinary team usually manages gliomas, including neurosurgeons, neuro-oncologists, and radiation specialists. 

Surgical Resection 

Surgery is the first-line treatment whenever possible. 

• Goal: Maximal safe resection while preserving brain function 

• Benefit: Greater resection extent correlates with longer survival 

• Low-grade gliomas: Early surgery improves seizure control and longevity 

Radiation Therapy 

• Standard for high-grade gliomas following surgery 

• Typically 60 Gy over six weeks using external beam radiation 

Chemotherapy 

• Temozolomide (TMZ): The standard chemotherapy used alongside radiation in the Stupp protocol for glioblastoma 

• PCV regimen (procarbazine, lomustine, vincristine): Especially beneficial in 1p/19q codeleted oligodendrogliomas 

• MGMT methylation predicts a better response to alkylating agents like TMZ 

Targeted and Novel Therapies 

• Bevacizumab (Avastin): Anti-VEGF agent used for recurrent glioblastoma, helps manage symptoms though not proven to extend survival 

• Tumor Treating Fields (TTF): Alternating electric fields that disrupt tumor cell division and may improve survival when combined with standard therapy 

Supportive and Rehabilitative Care 

• Corticosteroids (e.g., dexamethasone): Reduce brain swelling 

• Antiepileptic drugs: Manage seizures 

• Physical and speech therapy: Aid in recovery and function 

Clinical Trials 

Participation in clinical trials is encouraged to access innovative treatments such as immunotherapies, gene therapies, and precision-targeted drugs. 

Gliomas and their treatments can cause several complications, including: 

• Increased intracranial pressure and herniation 

• Seizures 

• Cognitive decline and personality changes 

• Focal neurological deficits 

• Hydrocephalus 

• Blood clots (venous thromboembolism) 

• Radiation necrosis and chemotherapy toxicity 

Glioma outcomes depend on tumor type, grade, molecular markers, and extent of surgical removal. 

Median survival times: 

• Low-grade gliomas: 5–15 years 

• Anaplastic gliomas (Grade III): 2–5 years 

• Glioblastoma (Grade IV): 12–18 months 

Favorable factors include: 

• Younger age (<40 years) 

• Good performance status 

• IDH mutation positivity 

• 1p/19q codeletion 

• MGMT promoter methylation 

High-grade gliomas almost always recur despite treatment, highlighting the urgent need for better therapies. 

Currently, there are no proven ways to prevent gliomas. However: 

• Avoiding unnecessary exposure to ionizing radiation may lower risk 

• Families with hereditary cancer syndromes should consider genetic counseling 

Healthy lifestyle measures such as balanced nutrition, regular exercise, and stress reduction may contribute to overall brain health, although they have not been shown to directly prevent gliomas. 

Living with a glioma can be physically and emotionally challenging. A strong support network, open communication with the care team, and practical strategies can help maintain quality of life. 

Tips for patients and caregivers: 

• Stay informed about treatment options and side effects 

• Keep a symptom journal to discuss with your doctor 

• Seek rehabilitation to address speech, movement, or memory difficulties 

• Join support groups or counseling programs 

• Prioritize nutrition, rest, and emotional wellbeing 

Palliative care should also be introduced early to manage symptoms, enhance comfort, and support families. 

Gliomas represent one of the most complex and aggressive types of brain tumors. While progress has been made in understanding their molecular basis and improving treatment strategies, outcomes remain limited—especially for high-grade gliomas like glioblastoma. Early detection, precise molecular diagnosis, and individualized care plans are key to improving survival and quality of life. 

Ongoing research in genetics, immunotherapy, and targeted treatments continues to offer hope for better outcomes in the future. 

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3. Ostrom QT, Cioffi G, Gittleman H, et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2012–2016. Neuro Oncol. 2019;21(Suppl 5):v1–v100. 

4. Weller M, van den Bent M, Hopkins K, et al. EANO guideline for the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 2017;18(6):e315–e329. 

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