Headache & Pain
Headache associated with spontaneous spinal CSF leak
Nov. 20, 2023
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Headaches associated with intracranial neoplasms are common. This article discusses the epidemiology, pathogenesis, and clinical presentation of brain tumor-associated headaches. In addition, uncommon headache syndromes caused by brain tumors, headaches precipitated by the initial treatment of brain tumors, as well as headaches occurring as late complications of brain tumor treatment are described. The approach to new headaches in patients with known malignancies and the treatment of brain tumor headaches are briefly discussed.
Headache has been recognized as a common symptom of brain tumors for many years. In the 1940s, a series of classic papers described the clinical characteristics and mechanisms of brain tumor-associated headache (61; 49). With improved neuroimaging and the resultant earlier diagnosis, the spectrum of tumor-associated headache has expanded beyond these classical descriptions.
Features of brain tumor-associated headache. The classic brain tumor headache has been described as severe, early morning, or nocturnal headache with nausea and vomiting (47). In studies of unselected tumors, the associated headache characteristics vary, and there is no typical brain tumor-associated headache. Headache pain ranges from a dull ache to a pressure or tightening or a throbbing or shooting pain (28; 66; 76; 89).
The headache pain is usually intermittent, moderate to severe in intensity, and progressive (28; 66; 76; 89). Only about a third of patients have nocturnal or morning headaches or both, and 20% report headache exacerbation by Valsalva maneuvers (28; 66; 89). Nausea and vomiting are reported in 18% to 60% of patients (28; 66; 76; 89).
Headaches with features of primary headache disorders are found in a minority of patients. Migraine-type headaches are reported in up to 15% of patients, and these usually have atypical features, including middle-age onset, progressive pattern, association with Valsalva maneuver or lying down, nocturnal occurrence, and unresponsiveness to analgesic treatment (28; 66; 76; 89). Tension-type headaches were seen in 29% to 39% of patients (76; 89).
Overall, 62% of the children with brain tumors experienced chronic or frequent headache. Headache frequency was more common in children with infratentorial tumors (70%) than in children with supratentorial tumors (58%). Children with a brain tumor and headache had more symptoms and neurologic signs, such as nausea or vomiting, papilledema, or hypoactive tendon reflex. However, upper extremity weakness, optic atrophy, and irritability were less frequent (18).
Isolated headache with no other symptoms may be the first manifestation of a brain tumor, but it is unusual for patients not to develop other symptoms by diagnosis. In adults, only 2% to 8% of patients have isolated headache on presentation, and in a study of 183 patients, all patients had developed other symptoms within 10 weeks (90; 76; 89). Headache was the most common symptom (62%) in patients presenting with brain metastases as the first indication of systemic cancer (40).
A study of 3291 children with brain tumors found that fewer than 1% had headache as their sole symptom, and fewer than 3% had no neurologic abnormality on examination (18). In 2006, Wilne and colleagues reported that 41% of 200 children with brain tumors had headache at presentation, and all 200 children had other symptoms and signs (96).
Headache lateralization does not always predict tumor location. Pfund and colleagues found that headache lateralization predicted tumor location in only one third of patients, and 12% of patients with unilateral headaches had a contralateral tumor (66). In contrast, Forsyth and colleagues found that all patients with unilateral headache had an ipsilateral tumor (28). Frontal headaches were the most unreliable in predicting tumor location and were most common (28; 89). The reported frequency of bilateral headaches ranged from 18% to 72% (28; 66). Laterality of headache was predictive of tumor location with 82.8% of side-locked headache occurring ipsilateral to tumors. Among strict bilateral headache, 53.3% had bihemispheric tumors, and 25% had midline tumors (41).
The majority of patients with infratentorial tumors have supratentorial headaches only, but if occipital pain is present, an infratentorial tumor is more likely. Skull-based tumors were more often associated with frontal headache (66; 76; 89).
Among pediatric headache patients, accompanying vomiting, neurologic signs, and association of seizure had an increased risk of intracranial neoplasm. Previous headache history had a decreased risk of intracranial neoplasm (79).
Tumors of the skull base. Headache or head pain may be caused by metastatic disease in the base of the skull. Five syndromes have been described:
(1) Orbital syndrome: blurred binocular vision followed by proptosis, diplopia, supraorbital, and eventually external ophthalmoplegia.
(2) Parasellar syndrome: unilateral frontal headache, diplopia, ocular paresis, but no proptosis.
(3) Middle fossa or gasserian ganglion syndrome: pain, sensory change in the maxillary or mandibular division of the fifth cranial nerve, and diplopia. Motor involvement of the mandibular branch or headache was less common.
(4) Jugular foramen syndrome: pain including glossopharyngeal neuralgia, hoarseness due to vocal cord paresis, and palatal, tongue, or ipsilateral sternocleidomastoid or trapezius weakness or wasting.
(5) Occipital condyle syndrome: severe, localized, unilateral occipital pain; dysarthria or dysphagia due to unilateral twelfth nerve palsy (35; 16).
Headache or head pain has also been caused by occlusion of the superior sagittal sinus by lymphoma or other tumors and by occlusion of the temporal artery by metastatic lung carcinoma (31; 10; 57).
Uncommon headache syndromes as a symptom of brain tumors. Headache is reported in 72% of pituitary tumors (53). Trigeminal autonomic cephalalgias (TACS)-like headaches are reported more frequently than expected. In a case series of 84 pituitary tumor patients with troublesome headache, 76% had chronic or episodic migraine-like headache, 5% had short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)-like headache, 4% had cluster-like headache, 1% had hemicrania continua-like, and 27% had primary stabbing headache-like (54). Patients with prolactinomas and growth hormone-secreting tumors are reported to have more severe headaches than patients with nonsecreting tumors (53). Secondary trigeminal autonomic cephalalgias are reported with other tumors as well as neurovascular and other lesions. They may be indistinguishable from primary trigeminal autonomic cephalalgias, including their response to indomethacin and other therapies (94). Sometimes, the presence of a tumor in the cerebellopontine angle may be confusing, and the actual reason for the symptoms of trigeminal neuralgia may be the neurovascular conflict alone (87).
Cerebrospinal fluid obstruction and cystic brain lesions. Harris described severe paroxysmal headache relieved by changes in head position as the classic presentation of a colloid cyst (37). These benign tumors are of interest, as they may present with headache not associated with other symptoms and be unrecognized. Patients still die from colloid cysts when they present with catastrophic acute deterioration due to blockage of the foramen of Munroe by the pedunculated tumor. In a study of 78 symptomatic patients with newly diagnosed colloid cysts, 25 patients (32%) presented with acute deterioration, and five of these died. Four additional patients presented with sudden unexplained death caused by a colloid cyst for an overall mortality of 12% (22). In a study of 105 cases of colloid cysts, the classic description of the associated headache was uncommon, as 92% of patients reported generalized, intermittent headache, and only two patients had a postural component (21). Papilledema was found in 76% of patients, and ataxia, decreased vision, and urinary incontinence were present in 18% to 27%.
Pituitary tumors. Pituitary apoplexy caused by infarction or hemorrhage into a pituitary tumor presents with acute onset of intense headache associated with visual loss plus or minus ocular palsies, facial numbness, or somnolence and pituitary insufficiency (11; 88). Four of 42 patients (9.5%) with asymptomatic, nonfunctioning pituitary adenomas developed apoplexy over a 5-year observation period (05). Rarely, pituitary apoplexy proves fatal if unrecognized (80).
Tumor cysts may rupture, spilling their contents into the cerebrospinal fluid. Craniopharyngioma, dermoid, and epidermoid cyst ruptures have all been reported to cause headache due to the inflammatory meningeal reaction caused by the irritating cyst contents (75; 34; 85). The inflammation may be severe enough to cause death.
Although headaches are a common complaint in patients with pituitary lesions, the relationship between the symptom and underlying pathology remains unclear. With the exception of pituitary apoplexy, there is likely only a small subset of patients whose headaches result directly from pituitary disease, and this category has yet to be fully elucidated. Although in most cases, patient complaints can be attributed to a primary headache syndrome or other unrelated cause, the presence of endocrine dysfunction, recent visual changes, or new-onset trigeminal autonomic cephalalgia mandates further workup with imaging (23). Prospective evaluations indicate that risk factors for the development of headache in the setting of pituitary adenoma include highly proliferative tumors, cavernous sinus invasion, and personal or family history of headache. Migraine-like headaches are the predominant presentation. Unilateral headaches are often ipsilateral to the side of cavernous sinus invasion (86).
In most cases, the prognosis of brain tumor-associated headache depends on the prognosis of the underlying tumor.
The etiology of brain tumor-associated headache is multifactorial, including direct physical structural changes, tumor secretions, and side effects of treatment.
In 1940, Ray and Wolff mapped the pain-sensitive structures of the head in a series of patients undergoing craniotomies (69). From these experiments, they postulated six mechanisms of headache pain:
(1) traction on the veins draining into the large venous sinuses with resulting displacement;
(2) traction on the middle meningeal artery;
(3) traction on the major arteries at the base of the brain;
(4) direct pressure on cranial nerves with afferent pain fibers from the head;
(5) distension and dilation of the intracranial and extracranial arteries;
(6) inflammation in or around the pain-sensitive structures of the head.
(7) ictal epileptic episode caused by intracranial tumor
Studies of an additional 67 patients with brain tumors concluded that local and distant traction on pain-sensitive structures, mass effect, and hydrocephalus caused most headaches (49).
The evidence for raised intracranial pressure as a cause for headache is mixed. In migraineurs, raising cerebrospinal fluid pressure abolished the headache induced by intravenous histamine (78). However, raised intracranial pressure induced by saline infusions caused headache in other studies (83). Headaches, dizziness, and alterations in consciousness and motor control triggered by standing are symptoms of plateau waves, which are acute elevations in intracranial pressure (93).
Not all brain tumor-associated headaches are caused by traction on pain-sensitive structures and mass effect. Patients with pituitary tumors frequently have headaches, but Levy and colleagues reported no association between pituitary volume and headache or between cavernous sinus invasion and headache (53). Headaches experienced by patients with growth hormone-producing tumors may respond to treatment with somatostatin analogues. In prolactinomas, dopamine agonists may either improve or exacerbate headache (54). It has been postulated that expression of somatostatin receptors coupled to the pain pathways may cause headaches (51), but other studies by the same group have found no association between vasoactive intestinal polypeptide, calcitonin gene-related peptide, and substance P expression and headache in pituitary tumors (52; 59).
Headache is a common symptom of intracranial hemorrhage (ICH); however, hemorrhage into a brain tumor is an infrequent cause of spontaneous intracranial hemorrhage (< 10%). In a study of 208 cancer patients with intracranial hemorrhage, 61% of them have bled into a brain tumor; headache is a presenting symptom in 40%. Most hemorrhages (77%) were in solid tumors, especially melanoma, lung cancer, breast cancer, and renal cell carcinoma. Twenty-one percent of them were in primary brain tumors, especially glioblastoma and oligodendrogliomas (60).
Other possible mechanisms for headache in intracranial tumors include infarction or infection of tumor and treatment-related mechanisms (60; 82). Treatment-related headache mechanisms will be discussed later in this review.
In a case report of a patient with a hippocampal tumor, headache attacks occurred only during ictal activity monitored by electroencephalography (07). This finding suggested that ictal epileptic episode could cause headache in patients with intracranial neoplasm.
The prevalence of headache associated with brain tumors varies widely depending on the tumor’s location and type and the patient’s age. Most studies report headache at presentation only.
In studies of unselected tumors in adults, headache prevalence ranges from 48% to 71% (28; 66; 20; 76; 89). The prevalence has remained relatively constant despite changes in neuroimaging techniques and greater availability. This suggests that headache is an early symptom in adults with brain tumors. In contrast, headache was reported in only 33% of children in a meta-analysis of later papers from 1991 to 2005 reporting signs and symptoms of childhood brain tumors at presentation versus 62% in an earlier study (18; 95).
The prevalence of headache varied with tumor location: intraventricular and midline tumors (92% to 95% had headache), infratentorial tumors (70% to 84%), and supratentorial tumors (55% to 60%) (18; 66; 95).
Factors that predict increased risk of headache in patients with brain tumor other than location include raised intracranial pressure, degree of midline shift, and increasing edema (28; 66). The relationship between tumor size and the likelihood of headache is uncertain. Similar to the results of Forsyth and Posner, Valentinis and colleagues found that within similar pathologies, increased size was associated with increased risk of headache, but others did not have similar findings (66; 53; 76; 89). In my experience, when an individual patient has a brain tumor-associated headache, the headache worsens as the tumor grows.
A prior history of headaches also predicts an increased risk of headache with a brain tumor (28; 89). Schankin and associates reported an alteration of headache in 82.5% of patients with preexisting headache. Interestingly, 18% reported marked relief of their preexisting headache. Only 38% of patients without preexisting headache developed headache (76). Forty-nine percent of patients with headaches and pituitary tumors had a family history of a headache disorder (54).
Both the elderly and the very young are less likely to present with headache. Only 8% of patients over the age of 75 had headache (56), compared with 44% of those 18 to 24 years of age. At least 72% of children aged 4 to 20 years had headache, but only 8% of those younger than 1 year had headache (18).
A new or changed headache experienced by a patient with a known systemic malignancy should be investigated. One study reported intracranial metastases in 32.4% of 68 cancer patients with new or changed headache (19). Emesis, headache duration of less than 10 weeks, and non-tension-type headache pain were independent predictors of metastases but had low specificity (19). Argyriou and colleagues reported on 54 patients with new or changed headache, 54% of whom had intracranial metastases. In their series, emesis, bilateral frontotemporal headache, pulsating quality, moderate-to-severe intensity, duration of 8 weeks or longer, gait instability, and extensor plantar responses were independent predictors of brain metastases (04). In children with systemic cancer and new headache, only 12% of headaches were caused by brain metastases, and primary brain tumors were found in 1% (03).
Usually, headaches associated with brain tumors cannot be prevented, although they can be treated. The exception is the change in surgical techniques used to reduce headache frequency after posterior fossa craniotomy.
Approach to headache in cancer patients. All cancer patients with new headache should be assumed to have brain metastases until proven otherwise. Cancer patients are also at risk for hemorrhage into a tumor as well as venous sinus thrombosis and cerebral infarcts. In a series of 208 cancer patients with intracerebral hemorrhage, 61% hemorrhaged into a brain tumor, most commonly melanoma, lung, breast, and renal cell carcinoma (60). Immunosuppression increases the risk for infection, including meningitis or opportunistic infections. Cancer patients are not immune to the primary headache disorders.
Headaches have been reported by 30% to 40% of patients with leptomeningeal metastases, often associated with multifocal neurologic signs and symptoms, as well as pain in a spinal, radicular, or meningeal pattern (92; 08; 39). Patients may present with headache due to raised intracranial pressure or a diffuse encephalopathy without focal signs (36). An increasing incidence of CNS metastases, including leptomeningeal disease, has been noted in patients treated with gefitinib for non-small cell lung cancer and trastuzumab for breast cancer (09; 62). Breast, lung, melanoma, leukemia, and lymphoma are the most common systemic tumors associated with leptomeningeal spread (39), whereas ependymomas, medulloblastomas, pineal region tumors, and primary CNS lymphomas are the most common primary brain tumors.
Abraham and colleagues reported a series of 33 patients with a nonmetastatic manifestation of lung cancer causing severe unilateral ear, face, and temporal pain. It was thought to be caused by local tumor invasion of the vagus nerve or compression by enlarged lymph nodes in the mediastinum (02). Evans proposed the term “vagal cephalgia” to include headache or facial pain from vagal efferent stimulation from cancer or myocardial ischemia (25).
New headache in patients without known malignancy. The evaluation of new headache in patients without known malignancy is beyond the scope of this review. The risk of brain tumors in patients with new undifferentiated headache is low (0.15%) and is even less in those with headache that meets the criteria for a primary headache disorder (0.045%) (45). Briefly, patients with new or changed headache and new neurologic signs or systemic symptoms should be assessed for serious or life-threatening headache causes, including brain tumors (68). Older patients, those with progressive headache, emesis, meningismus, nocturnal or early morning headache, and patients whose headache worsens with Valsalva maneuver or exertion should raise an increased index of suspicion for a secondary cause for headache (67; 66). Patients with a new diagnosis of trigeminal autonomic cephalalgia should be screened for pituitary or cavernous sinus lesions (47).
Headache due to treatment of brain tumors. Treatment-related causes of headache in brain tumor patients include postcraniotomy pain (27; 82), other complications of surgery, radiotherapy, chemotherapeutic agents, antiemetics, and corticosteroid withdrawal. Possible treatment-related mechanisms for brain tumors include postcraniotomy headache, reversible leukoencephalopathy syndrome (PRES), pseudotumor cerebri, cerebral venous thrombosis, chemical meningitis, and biological agent-induced mechanisms (Table 1).
Reversible posterior leukoencephalopathy (PRES)
Cyclophosphamide, Ara-C, cis-paltinum, ifosfamide, vincristine, gemcitabine, bevacizumab
Cerebral venous thrombosis
Interferons, interleukins, tamoxifen
Persistent headache-attributed craniotomy was listed in the third beta edition of the international classification of headache disorders (code 5.5). It was renamed from chronic postcraniotomy headache in the second edition of the International Classification of Headache Disorders (38). Persistent postcraniotomy headaches are uncommon in patients with supratentorial craniotomies (43; 30). In a series of 71 patients with craniotomy for aneurysms, 48% had craniofacial pain and functional jaw limitations 4 to 6 months after craniotomy (71). Similar jaw and craniofacial pains are common in brain tumor patients (personal observation).
Suboccipital craniotomies are associated with a much higher prevalence of postoperative headache. A survey of 1657 patients who had surgery for an acoustic neuroma found that a third had preoperative headache, 78% to 93% had headache 3 months postoperatively, depending on the surgical approach, and 50% to 66% continued to have headache 3 years postoperatively (73). In another study, 64% of patients reported postoperative headache after acoustic neuroma surgery; this persisted in 55% (70).
Despite normalizing prolactin levels, dopamine agonists may worsen headaches (54). Patients treated with octreotide for acromegaly may develop rebound headache after initial response (54).
Temozolomide is an alkylating agent used for malignant gliomas and other brain tumors and is reported to cause headache in 25% of patients (58; 98). Pseudoprogression, which occurs when temozolomide is used concurrently with radiotherapy for treatment of glioblastoma, presents with headache and neurologic deterioration starting shortly after completion of radiotherapy. Imaging shows increased enhancement and mass effect indistinguishable from recurrent tumor. Pseudoprogression usually responds to increased doses of corticosteroids and likely represents an enhanced response to treatment as these patients have longer survival rates than those who do not show pseudoprogression (15).
Posterior reversible encephalopathy syndrome (PRES) has been reported in patients treated with bevacizumab, which is a monoclonal antibody that binds to vascular endothelial growth factor and is used to treat malignant gliomas (55). PRES has also been reported with other targeted therapies. Other chemotherapeutic agents, including cyclophosphamide, Ara-C, cis-platinum, ifosfamide, vincristine, and gemcitabine, were reported to be associated with PRES, which may cause headache (82).
Retinoids are associated with an increase of intracranial pressure (pseudotumor cerebri), and L-asparaginase agents may cause cerebral venous thrombosis. Both pseudotumor cerebri and cerebral venous thrombosis can cause headache (82).
Intrathecal chemotherapy can cause chemical meningitis in as many as 25% of patients (32; 82). Corticosteroid withdrawal may precipitate headache despite no worsening of tumor-related cerebral edema. Selective serotonin type-3 receptor antagonists, such as ondansetron, are used to control chemotherapy-related nausea and may cause headache in 14% to 39% of patients (24; 42).
Radiotherapy to the brain may cause headaches at several different stages. An acute radiation encephalopathy with headache may occur at the onset of therapy. At 1 to 6 months postradiotherapy, a subacute demyelinating radiation encephalopathy may present with headache and worsening symptoms and signs (77). Imaging may show increased cerebral edema and gadolinium enhancement that is indistinguishable from recurrent tumor on standard CT or MRI. Delayed complications include cerebral radiation necrosis, which presents months to years after radiation and presents with headache and other focal symptoms depending on the location of the lesion (72).
Several reports of stroke-like migraine attacks after radiation therapy (SMART syndrome) occurring as a late complication of radiotherapy have been published (81; 12; 44; 06). Initially reported by Shuper and colleagues, these patients have prolonged and usually reversible episodes lasting hours to weeks of migraine-type headache and focal neurologic deficits, including seizures (81). The episodes may start many years after radiotherapy. MRI often shows striking ribbon-like cortical enhancement of the involved hemisphere, which resolves as the episode abates. Some SMART syndrome cases progressed after onset of symptoms (13). The exact mechanism of SMART syndrome is not well known. Supposedly, the main pathophysiologic factors involve white matter necrosis, vascular endothelial damage, mitochondrial dysfunction, demyelination, and gliosis, all secondary to delayed irradiation injury (64). There is a case report of SMART syndrome in a patient with previous surgical removal of cerebellar medulloblastoma and radiation therapy 17 years ago. His magnetic angiography revealed multiple stenoses of distal vasculature on both middle and posterior cerebral arteries, with leptomeningeal enhancement in headache side. Multiple stenosis of vasculature and leptomeningeal enhancement reverse after 2 years. Therefore, “reversible cerebral vasoconstriction syndrome”-like vascular changes work in the pathogenesis of SMART syndrome (07).
There are many causes of new headache in cancer patients, including intracranial metastases, side effects of therapy, hemorrhage, infarction, infection, and metabolic causes (46). After a careful history and physical examination, neuroimaging is essential in ruling out structural causes, such as metastases. MRI with gadolinium enhancement is superior to CT scan in detecting parenchymal metastases or leptomeningeal disease, and MRA/MRV sequences are better for detecting venous sinus thrombosis (17), whereas a CT scan may be better for acute hemorrhage or base of skull lesions. If imaging studies are negative and the clinical picture is compatible, lumbar puncture, measuring opening pressure, glucose, protein, and cell count in the CSF, as well as cytological examination of the CSF may reveal leptomeningeal metastases. A significant false negative rate of 25% to 50% exists for both CSF cytology and MRI scans, so studies may need to be repeated (92; 36).
The workup of secondary trigeminal autonomic cephalalgias may be indistinguishable from primary trigeminal autonomic cephalalgias, so neuroimaging should be considered to rule out secondary causes (94). The workup of other new headache patients without known malignancy is beyond the scope of this review.
Management of headache associated with brain tumor depends on the tumor pathology, location, associated symptoms, and the patient’s functional status. For headaches caused by raised intracranial pressure and mass effect secondary to tumor-associated edema, corticosteroids such as dexamethasone often provide dramatic symptomatic relief until more definitive therapy can be used. Potential complications of corticosteroids, such as avascular necrosis of the hip, should be discussed with patients.
Patients with brain metastases are frequently treated with whole-brain radiotherapy. In an early study of patients with brain metastases, 82% had relief of headache with palliative radiotherapy (14), but in one study, only 41% had a significant improvement in headache after radiotherapy (97). Two prospective studies have suggested that improvement or stabilization of headache and lower requirements for corticosteroids were seen after whole-brain radiotherapy (97; 84). Surgical resection or stereotactic radiosurgery may provide additional benefit in patients with limited numbers of metastases and controlled systemic disease (65; 48; 74).
Cerebral edema due to a primary brain tumor often responds to corticosteroids temporarily with good headache relief. Headaches may also respond to simple analgesics, although antiplatelet agents should be avoided by patients using corticosteroids or whose tumors have hemorrhaged. More definitive treatment depends on tumor pathology but may include surgery, radiotherapy, and chemotherapy. In my experience, treatment of malignant gliomas usually relieves headache but at recurrence, 26% to 52% of patients complain of headache (63; 33). Good palliative care should include adequate pain control using corticosteroids, and both simple analgesics and narcotics as required. Headache management is only one part of the symptom burden of progressive tumors, and palliative care support is essential for patients and their families.
Symptoms from radiation necrosis may respond to steroids, and surgery removing the necrotic tissue can be helpful. Bevacizumab is a monoclonal antibody active against vascular endothelial growth factor. In a small randomized trial, it was shown to be effective against radiation necrosis (50). There are no published reports of its use in SMART syndrome, but it may potentially be helpful.
Headache in patients with pituitary tumors showed variable response to treatment. In a case series, 73.7% of patients improved headache after surgical removal of tumors (01). Another study showed that 49% reported headache improvement after surgical treatment, 36% had no change of headache, and 8% worsened. Of the patients who underwent radiotherapy, only 6.25% had headache improvement. The use of somatostatin analogs resulted in 54.6% with headache improvement and 45.4% no change. The use of dopamine agonists improved headache in 30% and with worsening or no change in 30% (54).
Headache management of patients who are likely to have a long survival may be more complex. Patients with previous primary headache disorders are more likely to experience headache with a brain tumor (28). It is important to distinguish between headache caused by the brain tumor and headache from a primary headache disorder so treatment can be tailored appropriately. Occasionally, a secondary headache disorder will respond to therapies used for primary headache disorder (91; 29). Medical therapy for the tumor may also relieve the associated headache, as may be seen with the use of octreotide for growth hormone-secreting pituitary tumors and dopamine agonists for prolactinomas (54). Surgery even for pituitary microadenomas may relieve headache in patients who have failed medical therapy (26).
In summary, headaches associated with brain tumors can have many presentations, and a high index of suspicion is warranted when patients with a known malignancy present with a new headache. Certain rare headache syndromes, such as the trigeminal autonomic cephalalgias, appear to be more frequent in patients with brain tumors, and a secondary cause for these syndromes should always be ruled out by appropriate imaging. It is important to recognize that treatment of brain tumors may cause headache so as to avoid unnecessary investigations and patient anxiety. Finally, given the shortened life expectancy of many patients with brain tumors, it is critical to optimize symptom control quickly to maintain their quality of life.
Headaches may be associated with brain tumors in pregnant as well as nonpregnant women. Management of these headaches is subject to the same constraints as in pregnant women without brain tumors, where the risk to the fetus must be balanced against the risk to the mother. Decisions about the timing of definitive brain tumor treatment will depend on the woman’s wishes, risk, and surgical judgment.
The presence or absence of headache in isolation is unlikely to change anesthetic management during surgery for brain tumors. However, the factors that make a patient more prone to brain tumor-associated headache, such as raised intracranial pressure and mass effect, may change management during surgery. As in any surgery, good postoperative pain control is necessary.
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Ravi Uniyal MD DM
Dr. Uniyal of King George's Medical University has no relevant financial relationship to disclose.See Profile
Shuu-Jiun Wang MD
Dr. Wang of the Brain Research Center, National Yang-Ming University, and the Neurological Institute, Taipei Veterans General Hospital, has no relevant financial relationships to disclose.See Profile
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