Low grade Gliomas

Low-grade gliomas (LGGs) are primary brain tumors arising from glial cells and are generally classified as World Health Organization (WHO) Grade 2 diffuse gliomas. They are slow-growing tumors that commonly affect young and middle-aged adults. Although they have a relatively favorable prognosis compared with high-grade gliomas, they possess the potential for recurrence and malignant transformation. Early diagnosis, maximal safe surgical resection, and appropriate long-term surveillance are essential to optimize neurological function and improve survival.

Epidemiology

Low-grade gliomas account for a significant proportion of primary brain tumors in young adults. They commonly present between the third and fifth decades of life and affect both males and females. The majority eventually demonstrate progressive growth or malignant transformation over time.

Risk factors

Risk factors for low-grade gliomas include:

• Increasing age

• Family history of glioma

• Genetic syndromes such as Li-Fraumeni syndrome and Neurofibromatosis type 1

• Previous exposure to ionizing radiation

• Certain inherited cancer predisposition syndromes

Pathophysiology

Low-grade gliomas arise from glial precursor cells and are characterized by slow but infiltrative growth within the brain parenchyma. Despite their relatively indolent nature, these tumors infiltrate surrounding normal brain tissue, making complete surgical excision difficult in some patients. Progressive tumor growth may lead to seizures, focal neurological deficits, increased intracranial pressure, and eventual malignant transformation into higher-grade gliomas.

Clinical presentation

The clinical presentation depends on the tumor location, size, and involvement of eloquent brain regions. Seizures are the most common presenting feature.

Symptoms

• Seizures

• Progressive headache

• Progressive neurological symptoms depending on tumor location

• Limb weakness

• Sensory disturbances

• Speech difficulties

• Cognitive or behavioral changes

• Visual disturbances

• Gait imbalance

Clinical signs

• Focal neurological deficits

• Motor weakness

• Sensory deficits

• Aphasia

• Visual field defects

• Cranial nerve deficits (depending on tumor location)

• Cognitive impairment

• Papilloedema in patients with raised intracranial pressure

Differential diagnosis

• High-grade glioma

• Brain metastases

• Meningioma

• Primary central nervous system lymphoma

• Brain abscess

• Demyelinating disease

• Cerebral infarction

• Cortical dysplasia

• Dysembryoplastic neuroepithelial tumor (DNET)

Diagnostic criteria

The diagnosis of low-grade glioma is based on clinical presentation, neuroimaging findings, and histopathological confirmation following biopsy or surgical resection.

Diagnosis is established by:

• Clinical features compatible with a slowly progressive intracranial lesion.

• MRI or CT demonstrating imaging characteristics consistent with a low-grade glioma.

• Histopathological confirmation and WHO classification following tissue diagnosis.

Investigations

• CT scan of the brain

• MRI of the brain

• MR spectroscopy

• Diffusion tensor tractography (DTI)

• Histopathological examination following biopsy or surgical resection

• Molecular testing where available (e.g., IDH mutation status and 1p/19q codeletion)

Management

Management aims to achieve maximal safe tumor removal, preserve neurological function, control seizures, delay tumor progression, and improve long-term survival.

Initial management includes:

• Assess airway, breathing, and circulation in critically ill patients.

• Perform a comprehensive neurological assessment.

• Control seizures where present.

• Obtain high-quality neuroimaging for surgical planning.

• Discuss management through a multidisciplinary neuro-oncology team.

Non-pharmacological treatment

Surgical management

• Maximal safe surgical resection is the preferred initial treatment whenever feasible.

• Complete tumor removal is associated with long-term survival approaching 100%.

• Following partial resection, reported survival rates range from approximately 80–90% at 5 years, 70–80% at 10 years, and 50–60% at 20 years.

• Repeat imaging at 6, 12, and 24 months should be performed to monitor tumor growth.

• Repeat surgical resection should be considered if recurrent or progressive disease remains surgically resectable.

Radiotherapy

Radiotherapy is recommended when indicated following surgery or for residual disease.

Recommended radiotherapy schedule:

• 1.8 Gy × 28 fractions = total dose 50.4 Gy, administered 5 times per week.

If the hypothalamus or pituitary gland is included within the radiotherapy field, endocrine function should be evaluated annually by measuring:

• T4

• TSH

• Testosterone or FSH/LH

Pharmacological treatment

Seizure management

• Administer appropriate anticonvulsants in patients presenting with seizures.

Concurrent and adjuvant chemotherapy

Concurrent and adjuvant Temozolomide is indicated where available.

• Temozolomide – 75 mg/m² – PO – once daily during radiotherapy.

Then:

• Temozolomide – 150–200 mg/m² – PO – once daily on days 1–5 – repeated monthly – for 6 months.

Management according to underlying cause

Resectable low-grade glioma

• Maximal safe surgical resection is recommended.

Residual tumor following surgery

• Radiotherapy should be considered.

• Concurrent and adjuvant Temozolomide should be administered where available.

Progressive or recurrent tumor

• Repeat MRI to assess progression.

• Repeat surgical resection should be attempted if technically feasible.

• Consider additional radiotherapy or systemic therapy according to multidisciplinary team recommendations.

Tumors involving the hypothalamic-pituitary region

• Annual endocrine assessment is recommended following radiotherapy.

Referral

Refer all patients with suspected or confirmed low-grade glioma to a neurosurgical and neuro-oncology specialist.

Urgent referral is indicated for patients with:

• New-onset or uncontrolled seizures

• Progressive neurological deficits

• Features of raised intracranial pressure

• Rapid neurological deterioration

• Suspected tumor recurrence

• Significant radiological progression

Complications

• Recurrent seizures

• Progressive neurological deficits

• Raised intracranial pressure

• Tumor recurrence

• Malignant transformation to high-grade glioma

• Cognitive impairment

• Endocrine dysfunction following cranial radiotherapy

• Treatment-related neurological deficits

Prognosis

The prognosis depends on tumor size, location, extent of surgical resection, molecular characteristics, and response to treatment. Complete surgical excision is associated with excellent long-term survival. Patients undergoing subtotal resection remain at increased risk of recurrence and malignant transformation, requiring lifelong imaging surveillance.

Prevention

There are no established methods for preventing low-grade gliomas. Early evaluation of new-onset seizures or progressive focal neurological symptoms facilitates timely diagnosis and treatment. Long-term follow-up with serial MRI is essential for early detection of recurrence or progression.