Can Mesothelioma Cause Headaches? Features and Mechanisms

Headaches can occur in people with mesothelioma, but they are not among the most common primary symptoms of the disease; when headaches do appear, they typically arise from secondary causes such as treatment-related side effects, high blood pressure from targeted therapies (for example bevacizumab), or rare spread to the brain and its coverings. ^[1] Headaches tied to brain involvement or increased pressure inside the skull may present with morning predominance, nausea, vomiting, or neurological changes like vision problems or seizures. ^{[2] [3]}

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How Often and Why Headaches Happen

• Not a core symptom of mesothelioma itself: Mesothelioma most often presents with chest pain and breathlessness due to pleural effusion, rather than headaches. ^[4]
• Treatment-related causes (more common): Regimens that include bevacizumab can raise blood pressure, and severe hypertension may trigger headaches, dizziness, or shortness of breath. ^{[5] [6]} In rare cases, bevacizumab-based therapy can cause reversible posterior leukoencephalopathy syndrome (RPLS), which manifests with headaches, vision changes, confusion, seizures, and high blood pressure. ^{[7] [8]}
• Rare central nervous system (CNS) spread: Although pleural mesothelioma primarily affects the chest, it can rarely metastasize to the brain or meninges, leading to headache and focal neurological deficits. ^{[9] [10]} CNS involvement has been reported antemortem and at autopsy, and sarcomatoid subtypes may have a predilection for bloodborne spread. ^{[11] [12]}

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Typical Headache Features by Cause

1) Hypertension from Bevacizumab-Containing Therapy

• Features: Diffuse or throbbing headache, often accompanied by dizziness or shortness of breath when blood pressure is markedly elevated. ^{[5] [6]}
• Red flags: Severe or persistent headache with vision changes, confusion, or seizures suggests possible RPLS. ^{[7] [8]}
• Context: Blood pressure is usually monitored regularly during therapy, and urgent evaluation is advised for severe symptoms. ^{[5] [6]}

2) Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

• Features: Headache with visual disturbances, nausea/vomiting, confusion, seizures, and high blood pressure. ^{[7] [8]}
• Mechanism: Endothelial dysfunction and blood–brain barrier disruption lead to vasogenic edema in the posterior cerebral regions, producing the characteristic symptom cluster. ^{[7] [8]}
• Implications: RPLS is rare but potentially serious; prompt medical assessment is recommended. ^{[7] [8]}

3) Brain or Meningeal Metastases

• Features: Headache that may be worse in the morning, associated with nausea/vomiting, seizures, focal deficits (e.g., weakness on one side), vision changes, speech difficulties, or balance problems. ^{[2] [3]} Isolated case reports describe headache with progressive hemiparesis due to frontal lobe lesions. ^[9]
• Mechanism: Mass effect and increased intracranial pressure from tumors compress adjacent brain tissue and stretch pain-sensitive structures, producing headache; involvement of meninges and trigeminovascular pathways contributes to pain. ^{[13] [14]}
• Rarity: Historically considered uncommon, but longer survival and improved imaging have led to more recognized cases. ^{[10] [11]}

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Mechanisms of Headache in This Setting

• Raised intracranial pressure: Tumors or metastases increase pressure within the skull, causing morning-predominant headaches, nausea, and vomiting. ^{[3] [2]}
• Traction and inflammation of pain-sensitive structures: The dura and cerebral vessels are sensitive to traction and inflammatory mediators; tumor-related changes can trigger headache through trigeminovascular pathways and central sensitization. ^{[14] [15]}
• Endothelial injury and vasogenic edema (RPLS): Targeted therapies like bevacizumab may impair vascular integrity, leading to posterior brain edema and headache with neurological symptoms. ^{[7] [8]}
• Systemic hypertension: Elevated blood pressure itself can provoke headache, sometimes severely, during certain mesothelioma treatments. ^{[5] [6]}

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When Headache Warrants Urgent Attention

• Severe headache with neurological signs (vision changes, confusion, seizures, focal weakness) may reflect RPLS or intracranial metastasis and needs immediate evaluation. ^{[7] [8] [2]}
• New or worsening headaches during bevacizumab-containing regimens should prompt blood pressure checks and clinical review. ^{[5] [6]}
• Morning-predominant headache with nausea/vomiting or progressive focal deficits raises concern for intracranial mass effect. ^{[3] [2]} Case reports in mesothelioma describe headache with focal weakness due to brain lesions. ^{[9] [10]}

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Practical Evaluation and Management

• Clinical assessment: Document headache pattern, severity, triggers, and associated neurological symptoms; measure blood pressure during treatment cycles. ^{[5] [6]}
• Imaging: Brain MRI (preferred) or CT is reasonable if red flags are present or if neurological symptoms accompany headache. ^{[2] [13]}
• Therapy adjustments: Manage hypertension, consider withholding or modifying bevacizumab if RPLS is suspected, and treat seizures if present. ^{[5] [7]}
• Oncologic options for isolated brain lesions: Selected cases may benefit from surgical removal and radiotherapy, which have improved neurological symptoms in reports. ^{[9] [10]}
• Supportive care: For uncomplicated headaches, paracetamol (acetaminophen) can be used, while monitoring for escalation or new neurological signs. ^[16]

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Summary Table: Headache Causes in Mesothelioma

Cause	Typical Features	Mechanism	Action
Hypertension (bevacizumab)	Diffuse/throbbing headache; may have dizziness, dyspnea	Elevated BP during therapy	Check BP; adjust treatment if severe; urgent care for severe symptoms
RPLS	Headache with vision changes, confusion, seizures, high BP	Endothelial injury → vasogenic edema	Urgent evaluation; imaging; manage BP; hold offending agent
Brain/metastatic involvement	Morning-worse headache, nausea/vomiting, seizures, focal deficits	Mass effect ↑ intracranial pressure; meningeal irritation	Brain MRI/CT; consider surgery/radiotherapy
General tumor-related mechanisms	Headache from traction on dura/vessels; sensitization	Trigeminovascular activation; central/peripheral sensitization	Symptom-directed care; treat underlying lesion

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Key Takeaways

• Headache is usually secondary to treatment side effects (notably hypertension or RPLS) or rare brain spread rather than a primary mesothelioma symptom. ^{[4] [5] [7]}
• Red flags especially neurological changes or severe hypertension require urgent evaluation, as they may indicate RPLS or intracranial metastases. ^{[7] [2]}
• Mechanisms include increased intracranial pressure, trigeminovascular activation, endothelial dysfunction, and systemic hypertension, which together shape the clinical picture. ^{[14] [3] [7]}