Oligodendroglioma: Symptoms, Types, Causes and Treatment

Oligodendroglioma is a rare and intriguing type of brain tumor, arising from oligodendrocytes—the cells responsible for producing the protective myelin sheath around nerves in the central nervous system. As research advances, so does our understanding of how these tumors present, their underlying causes, and how best to treat them. This article offers a comprehensive guide to oligodendrogliomas, detailing their symptoms, types, causes, and the latest treatment approaches.

Symptoms of Oligodendroglioma

Oligodendrogliomas can be elusive in their early stages, often growing slowly before symptoms become noticeable. The signs depend on the tumor’s size, location, and rate of growth, making every patient’s experience unique. However, certain symptoms appear more frequently and can serve as early warning signals for clinicians and patients alike.

Symptom	Description	Frequency/Context	Source(s)
Headache	Persistent or recurring headaches	Most common initial symptom	1, 2, 5, 6
Seizures	Sudden, uncontrolled electrical activity	Often the first manifestation	1, 5, 6
Visual Loss	Blurred or lost vision, papilledema	Due to raised intracranial pressure	1, 2
Paralysis	Weakness or loss of movement	Focal neurological deficit	1, 2
Cognitive Changes	Memory, confusion, dementia	Progressive or sudden onset	1, 2
Ataxia	Loss of coordination	Less common but notable	1
Nausea/Vomiting	Gastrointestinal symptoms	Linked to increased intracranial pressure	2

Table 1: Key Symptoms

Common Presentations

The most frequently reported symptoms are headaches and seizures. Headaches result from increased pressure within the skull or direct irritation of brain tissue, while seizures stem from the tumor’s tendency to disrupt electrical activity in the cortical gray matter—especially in the frontal lobe, where these tumors most commonly arise 1, 5, 6.

Neurological Deficits

Depending on the tumor's location, patients might experience:

• Visual disturbances such as visual loss or papilledema (optic disc swelling due to raised intracranial pressure) 1, 2
• Focal neurological signs like paralysis, numbness, or weakness on one side of the body 1, 2
• Cognitive changes including confusion, memory loss, or in advanced cases, dementia 1, 2

Less Common Symptoms

While less prevalent, symptoms like ataxia (loss of coordination), hemorrhage, and even stroke have been documented. These might occur due to tumor growth impacting specific brain structures or causing bleeding 1.

Symptom Progression

Notably, symptoms do not reliably correlate with tumor grade—meaning both low- and high-grade tumors can present similarly. However, higher-grade tumors may cause more rapid symptom progression 1.

Types of Oligodendroglioma

Understanding the different forms of oligodendroglioma is vital for prognosis and treatment planning. Medical advances, particularly in molecular genetics, have refined how these tumors are classified.

Type	Distinguishing Features	Genetic Profile	Source(s)
Well-Differentiated (Grade II)	Slow-growing, less aggressive	IDH mutation, 1p/19q codeletion	5, 6, 7
Anaplastic (Grade III)	Faster-growing, more aggressive	IDH mutation, 1p/19q codeletion, 9p/CDKN2A loss	3, 5, 6, 7
Oligoastrocytoma	Mixed oligodendroglial and astrocytic cells	Variable, often lacks 1p/19q codeletion	3, 5, 6
Oligodendroglioma with Neurocytic Differentiation	Shows neuronal as well as glial features	Often 1p/19q codeletion	4

Table 2: Main Types of Oligodendroglioma

Well-Differentiated Oligodendroglioma (Grade II)

This classic form is slow-growing and generally has a better prognosis. It is characterized by:

• Involvement of the cortical gray matter, especially in the frontal lobe
• Frequent presence of seizures as a presenting symptom
• Radiological evidence of calcification in many cases
• Molecular signature: IDH mutation and co-deletion of chromosomal arms 1p and 19q 5, 6, 7

Anaplastic Oligodendroglioma (Grade III)

These are higher-grade, more aggressive variants with:

• Faster growth and greater tendency to recur
• Possible genetic alterations including additional loss of 9p and deletion of CDKN2A in addition to 1p/19q co-deletion and IDH mutation 3, 5, 6, 7
• Higher rates of neurological deterioration

Oligoastrocytoma

Oligoastrocytomas are mixed tumors containing both oligodendroglial and astrocytic cells. Their classification is evolving with advances in genetic testing, and many are now reclassified based on genetic markers. Oligoastrocytomas without 1p/19q co-deletion behave more like astrocytomas 3, 5, 6.

Special Variants: Neurocytic Differentiation

Rarely, oligodendrogliomas show features of neuronal differentiation, blurring the lines between glial and neuronal tumors. These cases often retain classic oligodendroglioma molecular signatures but may indicate a broader spectrum of tumor biology 4.

Causes of Oligodendroglioma

The development of oligodendroglioma is driven by a complex interplay of genetic, molecular, and possibly environmental factors. In recent years, key genetic hallmarks have been identified, revolutionizing diagnosis and therapy.

Cause/Factor	Description	Impact on Tumor	Source(s)
1p/19q Codeletion	Loss of chromosomal arms 1p and 19q	Defining, improves prognosis, enhances chemo-sensitivity	3, 7, 8, 9, 10
IDH Mutation	Mutation in isocitrate dehydrogenase genes	Universal in oligodendrogliomas, favorable outcome	7, 8, 15
CIC Mutation	Mutation of CIC gene on 19q13.2	Highly associated, may drive pathogenesis	8
Other Chromosomal Changes	Loss of 9p, 17p, CDKN2A deletion	Associated with progression and higher grade	3, 10
Environmental Factors	Not well defined	No clear risk factors identified	15

Table 3: Key Causative and Risk Factors

Chromosomal 1p/19q Codeletion

This hallmark genetic change defines modern oligodendroglioma diagnosis. The simultaneous loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q) is:

• Strongly associated with classic oligodendroglioma histology
• Predictive of better response to chemotherapy and longer overall survival
• Essential for distinguishing oligodendrogliomas from astrocytomas 3, 7, 8, 9, 10

IDH Mutation

Mutations in the isocitrate dehydrogenase (IDH) gene (IDH1 or IDH2) are found in virtually all oligodendrogliomas:

• Confer a better prognosis
• Play a role in tumor metabolism and epigenetic reprogramming
• Serve as a target for emerging therapies 7, 8, 15

CIC and Other Genetic Alterations

Mutation of the CIC gene on chromosome 19q13.2 is highly associated with oligodendroglioma and often co-occurs with 1p/19q codeletion and IDH mutation 8. Other changes, such as loss of 9p and deletion of the CDKN2A gene, are linked to tumor progression from lower to higher grades 3, 10.

Environmental and Other Factors

No definitive environmental or lifestyle risk factors have been identified for oligodendroglioma. Most cases appear to arise spontaneously due to acquired genetic mutations, rather than inherited predisposition 15.

Treatment of Oligodendroglioma

Management of oligodendroglioma has evolved dramatically, thanks to advances in molecular diagnostics and clinical trials. Treatment is tailored based on tumor grade, genetic profile, and the patient’s overall health.

Treatment	Main Use	Comments	Source(s)
Surgical Resection	Initial therapy for most patients	Maximal safe removal preferred	5, 6, 15
Radiation Therapy	Standard for grades II & III	Often combined with chemotherapy	14, 11
Chemotherapy (PCV)	Mainstay for 1p/19q codeleted tumors	PCV = procarbazine, lomustine, vincristine	11, 12, 14
Chemotherapy (TMZ)	Alternative to PCV in some cases	Temozolomide, especially for those intolerant to PCV	13, 14
Observation	Selected low-risk, low-grade cases	For patients with favorable features	15
Emerging/Targeted Therapies	Under investigation	IDH inhibitors, immunotherapy	15

Table 4: Current and Emerging Treatment Options

Surgery

Maximal safe surgical resection is almost always the first step. Benefits include:

• Reducing tumor mass and relieving symptoms
• Providing tissue for definitive histological and genetic diagnosis
• Potentially prolonging progression-free survival 5, 6, 15

Radiation Therapy

Radiation is a standard component for most grade II and III oligodendrogliomas—typically after surgery. It is particularly effective in tumors with 1p/19q codeletion and is often combined with chemotherapy for a synergistic effect 11, 14.

Chemotherapy

PCV Regimen

• PCV (procarbazine, lomustine [CCNU], vincristine) is the gold standard, especially for tumors with IDH mutation and 1p/19q codeletion.
• Combined radiotherapy and PCV chemotherapy significantly improve both progression-free and overall survival compared to radiation alone 11, 12, 14.

Temozolomide (TMZ)

• Used as an alternative for patients who cannot tolerate PCV
• May also be used in combination with radiation for higher-grade or recurrent tumors 13, 14

Observation (“Watch and Wait”)

Some patients with small, asymptomatic, and slow-growing tumors may be managed with careful observation and regular MRI scans, especially if surgical risks outweigh immediate benefits 15.

Emerging and Experimental Therapies

• Research is ongoing into IDH inhibitors and immunotherapies, aiming to exploit specific molecular vulnerabilities in these tumors 15.
• Clinical trials are exploring new combinations and targeted approaches, though standard treatment remains surgical resection followed by radiochemotherapy in most cases.

Treatment Decisions and Prognostic Factors

• The presence of 1p/19q codeletion and IDH mutation is associated with better response to therapy and longer survival.
• Individual treatment plans are tailored based on molecular profile, patient age, performance status, and tumor location 14, 15.

Conclusion

Oligodendrogliomas represent a fascinating intersection of clinical neurology, molecular genetics, and oncologic innovation. As our understanding deepens, so does our capacity to deliver more personalized and effective care.

Key Points Covered:

• Symptoms: Most commonly include headaches, seizures, and focal neurological deficits, but can range widely depending on tumor location and size.
• Types: Main subtypes are well-differentiated (grade II), anaplastic (grade III), and mixed forms, with molecular genetics now central to classification.
• Causes: Driven by distinctive genetic alterations, especially 1p/19q codeletion and IDH mutations, with other mutations influencing progression.
• Treatment: Multimodal and personalized; typically involves maximal safe surgery, followed by radiation and chemotherapy (PCV or TMZ), with emerging targeted therapies on the horizon.

By integrating clinical, radiological, and molecular information, clinicians can offer patients with oligodendroglioma the best chance of a favorable outcome, while research continues to improve both survival and quality of life.