Parents of children with new onset and/or frequent headaches are often concerned that their children may have brain tumors. Globally, nearly 60 % of children and adolescents experience significant headaches.1,2 In the United States, it is estimated that by 15 years of age, 57–82 % of children will have had a headache of any type.3 Most pediatric headaches are primary (i.e.: migraine or tension-type headache) and have no other underlying cause. The prevalence of migraines in patients between 15 and 25 years of age may be as high as 28 %.3,4 This makes pediatric headache one of the most common reasons for referrals in pediatric neurology clinics and in emergency departments5 whereas brain tumors in childhood are rare. Headache appears to be the most common presenting symptom of brain tumors in children, estimated to occur in approximately 33 % of patients.6-8However, it is rarely the sole presenting symptom of a brain tumor. A headache attributed to brain tumor is typically accompanied by additional symptoms such as focal neurological deficits, motor and visual system abnormalities, cognitive, behavioral and memory changes, seizures, abnormal gait, coordination difficulties, and signs of intracranial hypertension (nausea, vomiting, papilledema, vision changes).910 Weight loss, macrocephaly or abnormal head circumference growth velocity in infants, growth failure, and precocious puberty in older children may suggest presence of brain tumor.6

In addition to using ICHD-3 criteria, clinicians can perform thorough neurologic exams and search for "red flags" in a patient's headache history to evaluate whether a headache may be attributed to brain tumor. This approach may allow healthcare professionals to reassure patients and prevent unnecessary neurologic work-up, including imaging under general anesthesia. In this article we review the ICHD-3 criteria and current literature on the presentation of pediatric intracranial tumors, focusing on their application in pediatric headache medicine. We will also present the current guidelines for the management of migraine and other primary headaches in children which may be used for pediatric headache attributed to intracranial tumor. Although ICHD-3 uses the term “neoplasia” we are choosing to use the word “tumor” as is colloquially used by neurologists and oncologists.

The first systematic review and meta-analysis of symptom and sign patterns in children with central nervous system (CNS) tumors in 2007 by Wilne et al., revealed that the most frequent symptoms at diagnosis were headache (33 %), nausea and vomiting (32 %), abnormalities of gait and coordination (27 %), and papilledema (13 %).6 In 2020, a 14-country international collaborative case–control study in adolescents and young adults (10-24 years old) with brain tumors showed that headaches were the most frequent symptom (60 %).7 Another large epidemiological study in China demonstrated that nausea, vomiting, and headache were most common initial symptoms of brain tumors in patients aged 0-16 years.8

Relative to adults, children are more likely to present with the classic features of headache attributed to brain tumor (worse early in the morning or nocturnal headache, progressive, accompanied by nausea/vomiting).11, 12, 13, 14, 15

According to the ICHD-3, headache caused by one or more space occupying intracranial tumors requires at least two of the following: 1) evidence that the headache has worsened in temporal relation to the neoplasm or led to its discovery 2) significant worsening or improvement parallel to worsening or successful treatment of the neoplasm, or a headache with at least one of the following characteristics: The headache is progressive, worsens in the morning and/or when lying down, is aggravated by Valsalva-like maneuvers, and is accompanied by nausea and/or vomiting (Table 1).16

In the comment section of the ICHD-3, it is stated that the likelihood of headache attributed to brain tumor is greater in young patients (including children) and those with a history of primary headache. 16 Pathognomonic features of headache are not listed as key criteria in features of headache attributed to intracranial neoplasm in ICHD-3. The comments section emphasizes that progression or deterioration is a key feature. The other suggestive symptoms (severe, worse in the morning, accompanied by nausea and vomiting) are more likely to appear in the context of intracranial hypertension or with specific tumor types (i.e.: posterior fossa tumors).

In Wilne's systematic review for pediatric patients, increased intracranial pressure (ICP) is present in about 40 % of all intracranial tumors, 80 % of posterior fossa tumors, 60 % of centrally located tumors, 60 % of hemispheric tumors, 40 % of intracranial tumors in children under 4 years, 20 % of intracranial tumors in children with neurofibromatosis, 30 % of brainstem tumors, and 7 % of spinal-cord tumors. 6 Given these data, it is crucial to examine and document signs of increased ICP such as blurred/double vision, visual field defects, and papilledema in pediatric patients, even though these signs are not included in the ICHD-3 criteria.

Wilne et al., also summarized tumor location and specific combination of symptoms with headache.6 According to this meta-analysis, the frequency of headache was 67 % in posterior fossa tumors, 49 % in central tumors, 23 % in brainstem tumors, and 11 % in supratentorial tumors. However, the leading symptoms in posterior fossa tumors were nausea and vomiting for 75 % and abnormal gait and coordination difficulties for 60 %. In brainstem tumors, 78 % had abnormal coordination and gait difficulties. For central tumors, 21 % presented with abnormal eye movements.

In a prospective adult cohort study by Valentinis et al., 206 patients with intracranial tumors (aged 16-81, median 54) were interviewed by a neurologist to evaluate headache characteristics. Only 5.1 % of patients fulfilled the “classic criteria” of the intracranial tumor headache.14 Headache was non-specific (>50 %) or episodic tension-type headache (23.5 %) and episodic migraine without aura (13.3 %) which makes early diagnosis of tumor based on headache features problematic.

Previously, Forsyth and Posner reviewed headache features of 111 patients with primary or metastatic brain tumors (mean age 56). This study found that the "classic" early morning brain tumor headache was uncommon. Most patients (77 %) had tension-type headaches and 9 % had headaches with migraine-like features.17 A literature review from 2014 also revealed that brain tumor headache more often satisfies criteria for a primary headache such as migraine or tension-type. For this reason, the authors suggested that ICHD-3 criteria may miss a headache due to brain tumor.13 Consequently, some critics have suggested a new sub-criterion to include an evaluation of red flags as they are present in oncological patients.15

Taking a reliable headache history can be a challenge even for experienced headache specialists. Young children may not be able to give reliable history reading their visual and sensory symptoms.

A simplified approach to red flags for headache is described by the mnemonic SNOOP, introduced by Dodick et al., in 200318 and adapted to SNOOP4Y to guide imaging decisions for children with acute headache.19

According to the SNOOP4Y mnemonic, imaging would be warranted in children presenting with acute headache if 1 or more of the following red flags are present: (1) abnormal neurologic examination; (2) atypical presentation of the headache including vertigo, intractable vomiting, or headache waking the child from sleep; (3) a recent headache of less than 6 months; (4) a child less than 6 years of age; (5) no family history of migraine and/or primary headaches; (6) occipital headache; (7) a change in headache type; (8) subacute onset and progressive headache severity; (9) a new-onset headache in an immunosuppressed child; (10) first and/or worst headache; (11) systemic symptoms and signs, and (12) a headache associated with either confusion, mental status changes, or focal neurologic complaints (Table 2).19

The SNOOP4Y mnemonic serves as a helpful tool to identify red flags but should not be used in isolation. For example, a multicenter retrospective study found that age under six years is not a significant risk factor for malignant causes, suggesting that factors like age should be interpreted alongside clinical context and examination findings.20 According to guidelines from the American Academy of Neurology and the Practice Committee of the Child Neurology Society, routine diagnostic studies are unnecessary when the clinical history lacks associated risk factors and the child's neurologic examination is normal. Factors that predicted the presence of a space-occupying lesion included: (1) headache lasting less than one month, (2) absence of a family history of migraine, (3) abnormal findings on neurologic examination, (4) gait abnormalities, and (5) occurrence of seizures.21

Medication overuse headache is common in children and adolescents and should be considered prior to deciding on imaging. An estimated 20 % to 52.9 % of pediatric patients with chronic daily headache overuse medications.22, 23, 24, 25 In ICHD-3, a medication overuse headache is described as one that occurs on 15 or more days per month in a patient with pre-existing primary headache. This headache must develop because of overuse of acute or symptomatic headache medications, such as non-opioid analgesics or triptans.

With the lack of red flags in headache history, lack of headache features attributed to intracranial neoplasm according to ICHD-3 criteria, and normal neurologic, visual, and systemic examination, clinicians may focus on reassuring parents and work with them to manage their child's headaches. Patients will be well-served by having clinicians developed a preventive lifestyle plan, an acute treatment plan, encourage their patient to keep a headache diary, and address the possibility of a medication overuse headache. A re-evaluation is encouraged within 4-8 weeks to detect changes in headache features or any new neurological symptoms. To help guide decision making for neuroimaging and management of pediatric headache, we are proposing an algorithm that combines review of ICHD-3 criteria, a neurological exam, and review of pediatric headache history for red flags (Fig. 1).

The International Classification of Headache Disorders 3rd edition (ICHD-3) describes headache attributed to brain tumor as it relates to three syndromes.16 This includes colloid cyst of third ventricle, carcinomatous meningitis, and hypothalamic or pituitary hyper- or hypo-secretion. These syndromes frequently have acute life-threatening etiologies. Headaches attributed to pituitary apoplexy, craniotomy, and radiation surgery are included in the ICHD-3 appendix.

The pathophysiology of headache attributed to intracranial tumors in children is beyond this article's focus. Several pathophysiological mechanisms have been hypothesized for adult patients to understand the underlying mechanisms of brain tumor headache. The differences between the mature brain and the developing brain—particularly in the mechanics of pain-sensitive structures, peripheral and central sensitization mechanisms, and age-related changes in the hypothalamus and pituitary—make it challenging to apply these theories to children.

Headache attributed to colloid cyst of the third ventricle signals a life-threatening emergency.26 Third ventricular colloid cysts are rare and constitute about 0.5 to 1 % of all intracranial tumors.27 When immediately adjacent to the foramen of Monro, a colloid cyst can result in sudden obstructive hydrocephalus, causing headache with thunderclap onset, reduced level or loss of consciousness, and neurologic deterioration.16 This characteristic presentation should lead to rapid diagnosis. A retrospective analysis of 105 cases of third ventricle colloid cyst (age 10 to 68 years) showed that headache was the most common symptom, followed by papilledema, ataxia, diminished vision, and short-term memory disturbances.27 In a separate study of 5 pediatric patients with colloid cysts who underwent surgery, clinical manifestations included raised ICP, drop attacks, optic nerve atrophy, and worsened occipital headaches when reading.28 According to the ICHD-3, a headache attributed to colloid cyst improves in temporal relation to the successful treatment of the cyst.