Meningioma: Symptoms, Types, Causes and Treatment

Meningiomas are the most common type of primary brain tumor in adults. They originate from the meninges—the protective layers surrounding the brain and spinal cord. While many meningiomas are benign and slow-growing, their symptoms, types, causes, and treatment options can be complex and highly variable. In this article, we dive deep into the latest knowledge about meningiomas, drawing on recent research to give you a clear, comprehensive overview.

Symptoms of Meningioma

Meningiomas are notorious for their subtle onset. Some people may harbor these tumors for years before experiencing noticeable symptoms. The variety and severity of symptoms depend largely on the tumor's size, grade, and—most importantly—its location in the brain or spinal cord. Understanding these signs is crucial for early detection and effective management.

Symptom	Description	Influencing Factors	Source(s)
Headache	Persistent or worsening head pain	Tumor size, location, grade	1 5
Seizures	New or recurrent epileptic episodes	Cortical involvement	3 5
Visual Loss	Blurred or reduced vision, possible blindness	Tumor near optic pathways	2 5
Motor Deficits	Weakness, paralysis, or coordination issues	Tumor compressing motor cortex	3 5
Psychiatric	Mood, personality, or cognitive changes	Frontal/temporal lobe location	4 5
Sensory Loss	Numbness or tingling in limbs	Tumor location	1 3

Table 1: Key Symptoms

Common Presenting Symptoms

• Headache is one of the most frequent presenting symptoms, especially in larger or higher-grade tumors. The pain may be persistent or progressively worsen over time 1 5.
• Seizures occur in a significant subset of patients, particularly when the tumor involves or irritates the cerebral cortex 3 5.
• Visual disturbances such as blurred vision, visual field defects, or even blindness are common when meningiomas are near the optic nerves or visual pathways 2 5.
• Motor and sensory deficits—such as weakness, numbness, or difficulty with coordination—develop if the tumor compresses brain regions responsible for movement or sensation 3 5.
• Psychiatric and cognitive changes can be early or even isolated features, especially with tumors in the frontal or temporal lobes. These might present as mood swings, memory problems, or personality changes, often leading to initial psychiatric evaluation before neurological causes are considered 4 5.

Acute vs. Chronic and Intermittent Symptoms

• Most meningiomas cause slowly progressive symptoms due to gradual tumor growth and compression of brain tissue.
• However, in rare cases, symptoms can appear suddenly—such as stroke-like weakness—due to rapid tumor expansion or vascular compromise 3.
• Some patients experience intermittent, transient neurological deficits, which may recur over months before more persistent symptoms develop 3.

Location-Specific Manifestations

• Anterior visual system meningiomas primarily affect vision—often unilaterally at first, but may progress to bilateral involvement and blindness if untreated 2.
• Tumors in the frontal lobe may cause subtle personality or mood changes, while those in the temporal lobe might lead to memory disturbances or seizures 4 5.
• Cerebellar meningiomas can result in balance problems and coordination difficulties 1.

Factors Influencing Symptom Severity

• Tumor grade: Higher-grade (WHO II/III) meningiomas tend to present with more aggressive symptoms 5.
• Tumor size and location: Larger tumors and those located near critical structures (e.g., optic nerves, motor cortex) cause more pronounced symptoms 5.
• Venous blockage and edema: Swelling around the tumor or blockage of venous drainage can exacerbate symptoms 5.

Types of Meningioma

Understanding the different types of meningioma is essential for prognosis and treatment. Classification is based on histological (microscopic) appearance, tumor grade, anatomical location, and—more recently—molecular and genetic profiling.

Type/Grade	Description	Risk/Behavior	Source(s)
WHO Grade I	Benign, slow-growing	Low recurrence	5 7 8 9
WHO Grade II	Atypical, faster-growing	Higher recurrence	5 7 8 9
WHO Grade III	Anaplastic/malignant, aggressive	High recurrence/mortality	5 7 8 9
Location-based	Skull base, convexity, spinal, etc.	Dictates symptoms	6 7 9
Molecular Class	Defined by methylation/genetics	Guides prognosis	6 7 10

Table 2: Meningioma Types and Classifications

Histopathological Grading (WHO Classification)

• Grade I (Benign): The majority of meningiomas (~80–90%) are grade I and generally have the best prognosis, with low likelihood of recurrence after complete removal 7 8 9.
• Grade II (Atypical): These tumors grow more quickly, invade surrounding tissue, and are more likely to recur 5 7 8 9.
• Grade III (Anaplastic/Malignant): Rare but highly aggressive, with a significant risk of recurrence and poor survival outcomes 5 7 8 9.

There are 15 recognized meningioma subtypes, with nine assigned to grade I, and three each to grades II and III 7.

Anatomical Types

• Convexity meningiomas: Located on the surface of the brain; often easier to remove surgically.
• Skull base meningiomas: Arise near the base of the skull, often involving critical nerves and blood vessels; can be more challenging to treat 6.
• Spinal meningiomas: Occur along the spinal cord.

Molecular and Genetic Classification

• Recent advances have led to molecular classification systems, including DNA methylation profiling and mutation analysis (e.g., NF2, TRAF7, KLF4, AKT1, SMO). These classifications often predict tumor behavior and recurrence risk better than traditional histology alone 6 7 10.
• Four molecular groups have been identified, each with distinct biological and clinical characteristics (immunogenic, benign NF2 wild-type, hypermetabolic, and proliferative) 10.

Pathological and Genetic Features

• Certain genetic mutations (e.g., NF2 loss, chromosome 22q deletions) are associated with specific meningioma types and locations 6 8 9.
• Atypical and anaplastic meningiomas show more complex genetic alterations, with multiple chromosomal losses and gains 8 9.

Causes of Meningioma

Why do meningiomas develop? The answer is multifactorial, involving genetic, environmental, and possibly hormonal influences. While most cases appear sporadically, certain risk factors are well-established.

Cause/Risk Factor	Description	Evidence/Mechanism	Source(s)
Genetic (NF2, etc.)	NF2 gene mutations, chromosomal losses	Tumor initiation	6 8 9 11 13
Radiation	Previous cranial irradiation	DNA damage, tumorigenesis	11 14 19
Hormones	Estrogen/progesterone influences	Tumor growth modulation	11 13 19
Gender/Age	More common in women, middle-aged adults	Hormonal, unknown factors	2 11
Family History	Inherited susceptibility	Genetic predisposition	11 13

Table 3: Causes and Risk Factors

Genetic Factors

• NF2 Gene Mutations: About half of meningiomas harbor mutations in the NF2 gene, which encodes the tumor suppressor protein merlin. Loss of NF2 is a key step in tumor formation, especially in non-skull base tumors 6 8 9 11 13.
• Other Genetic Alterations: Mutations in TRAF7, KLF4, AKT1, and SMO are found in many skull base meningiomas, while higher-grade tumors often show complex genetic changes, including chromosomal losses (1p, 6q, 10, 14q, 18q) and gains 6 8 9.
• Hereditary Syndromes: People with neurofibromatosis type 2 (NF2 syndrome) have a markedly increased risk 11 13.

Environmental and Lifestyle Factors

• Radiation Exposure: High-dose cranial irradiation, even years earlier, is a well-established risk factor for meningioma 11 14 19.
• Hormonal Influences: Women are twice as likely as men to develop meningiomas. Many tumors have hormone receptors (estrogen, progesterone), suggesting a role for endogenous or exogenous hormones 2 11 13 19.
• Age and Gender: Most meningiomas occur in middle-aged and older adults, with a female predominance 2 11.

Other Possible Factors

• Family History: Although rare, familial cases point to inherited susceptibility and candidate DNA repair genes 11 13.
• Immunologic Factors: The influence of immune system factors on meningioma risk is largely unexplored 11.

Pathogenesis Overview

• Tumor initiation is linked to genetic inactivation of tumor suppressor genes, particularly NF2.
• Progression to more aggressive forms involves additional genetic and epigenetic changes, such as cell cycle dysregulation, telomerase activation, and alterations in growth factor signaling 12 13.

Treatment of Meningioma

Meningioma treatment is highly individualized, balancing the need for effective tumor control against the risks of intervention. The mainstay remains surgical removal, but radiotherapy, radiosurgery, and emerging medical therapies play important roles, especially for inoperable or recurrent tumors.

Treatment	Indication/Use	Outcome/Consideration	Source(s)
Observation	Small, asymptomatic, elderly patients	Regular monitoring	15 16 18 19
Surgery	Symptomatic or growing tumors	Potentially curative	1 15 16 18 19
Radiotherapy	Adjuvant, recurrent, or inoperable cases	Tumor control, not always curative	15 16 18 19
Radiosurgery	Small or residual tumors	Minimally invasive, precise	15 16 18 19
Medical	Refractory/recurrent, inoperable cases	Experimental, targeted agents	15 16 17 19

Table 4: Main Treatment Approaches

Observation ("Watchful Waiting")

• For small, asymptomatic tumors—especially in elderly patients or those with major health risks—active surveillance with regular MRI scans may be the best initial approach 15 16 18 19.
• Many meningiomas grow very slowly or not at all.

Surgery

• Surgical removal is the first-line treatment for most symptomatic or enlarging meningiomas and can be curative if the entire tumor (and involved dura) is removed 1 15 16 18 19.
• The goal is gross total resection, but in complex locations (e.g., skull base, near critical vessels/nerves) subtotal removal may be necessary to preserve function 1 18.
• Preoperative embolization can reduce surgical bleeding in selected cases 18.

Radiotherapy and Radiosurgery

• Conventional radiotherapy is indicated for residual, recurrent, or inoperable tumors, as well as higher-grade meningiomas 15 16 18 19.
• Stereotactic radiosurgery (e.g., Gamma Knife) is often used for small tumors or tumor remnants. It is non-invasive and highly targeted 15 16 18 19.
• Combined approaches (surgery plus radiotherapy or radiosurgery) are increasingly common, especially for challenging or recurrent tumors 15 18.

Medical Therapies

• Chemotherapy and hormone therapy have shown limited effectiveness and are not standard treatments 15 16 17 19.
• Targeted molecular therapies (e.g., inhibitors of vascular endothelial growth factor) are under investigation for refractory or recurrent cases, with some promise but no established role yet 15 16 17 19.
• Ongoing clinical trials are exploring new pharmacological and immunotherapeutic strategies 15 17 19.

Emerging Directions

• Molecular profiling of tumors is beginning to guide prognosis and, potentially, personalized therapy, especially for aggressive or treatment-resistant meningiomas 6 7 10 19.
• Future approaches may include antiangiogenic drugs, peptide receptor radionuclide therapy, and other targeted agents 15 17.

Conclusion

Meningiomas are a diverse group of tumors that, while often benign, can have significant health impacts depending on their size, location, and biological behavior. Recent advances in molecular diagnostics and targeted therapies hold promise for better outcomes in the future.

Key Points:

• Meningioma symptoms vary widely and depend on tumor location, size, and grade, ranging from headaches and seizures to vision loss and personality changes 1 2 3 4 5.
• The World Health Organization classifies meningiomas into three grades, with additional subtypes and molecular classes now recognized for better prognostication 7 8 9 10.
• Causes include genetic mutations (especially NF2), prior radiation exposure, hormonal factors, and possibly inherited predisposition 6 8 9 11 13 14.
• Treatment is tailored to the individual, with surgery and radiotherapy as mainstays; observation is appropriate for many, and new molecular therapies are under development 15 16 17 18 19.
• Ongoing research into the molecular biology of meningiomas is improving diagnosis, risk stratification, and therapeutic options for patients 6 7 10 19.

Understanding meningiomas is a rapidly evolving field. Staying informed about the latest advances can empower patients and caregivers to make well-informed decisions about care and treatment.