Acute headache: diagnosis

Identifying secondary headaches
Article section 4 of 11.  Previous  Next

By Stephanie J Nahas MD

Herein we discuss common red flags, the differential diagnoses suggested by these red flags, and the appropriate investigation required by each one. It is important to emphasize that red flags indicate an increased probability of secondary headache. The presence of a red flag increases the need to perform further investigation, but the patient must be analyzed in the context of the overall clinical picture. Certain “comfort signs,” such as acknowledgement of a typical headache trigger, a family history of similar headaches, or the presence of typical signs and symptoms of a primary headache disorder may offset minor red flags. Some clinical scenarios may erroneously prompt the clinician to ascribe a secondary diagnosis, leading to incorrect treatment.

(1) Sudden onset of severe headache (thunderclap headache). The sudden onset of a severe (explosive) headache must be investigated. Although not the most common cause of thunderclap headache, subarachnoid hemorrhage is the most feared. A meta-analysis showed that 10% to 43% of patients with subarachnoid hemorrhage demonstrate thunderclap headaches (incidence varies in different settings) (Polmear 2003). More recent studies have also identified the following features as predictive of subarachnoid hemorrhage: age greater than 40, witnessed loss of consciousness, neck stiffness, onset during exertion, vomiting, blood pressure greater than 160/100, and arrival by ambulance (Perry et al 2010; Perry et al 2013). All patients with thunderclap headache should have an expedient and exhaustive search for an underlying cause. These include serious intracranial vascular disorders, such as aneurysmal subarachnoid hemorrhage, intracerebral hemorrhage, cerebral venous (or sinus) thrombosis, arteriovenous malformation, arterial dissection (intra- and extracranial), CNS angiitis, pituitary apoplexy, and reversible cerebral vasoconstriction syndrome, which is increasingly recognized as a cause of recurrent thunderclap headaches (Calabrese et al 2007). Other organic causes of thunderclap headache are colloid cysts of the third ventricle, CSF hypotension, acute sinusitis (particularly with barotrauma), and meningoencephalitis (Ju and Schwedt 2010).

A thunderclap headache evaluation should include CT and a lumbar puncture if the CT is negative. Many clinicians will then order an MRA or CTA. Some authors argue that all patients with explosive headache should be evaluated with conventional angiography even when all the other examinations (including MRA) are normal (Linn and Wijdicks 2002; Polmear 2003). However, as noninvasive vascular technology has improved greatly in recent years, this argument loses some strength (Chen et al 2008; Grayev et al 2009).

CT is often inadequate for diagnosing a sinus or venous thrombosis, and MRV or CTV is necessary to exclude this disease. When pituitary apoplexy is suspected, views of the sella turcica should be requested.

When a patient with a thunderclap headache has a completely negative work-up, a diagnosis of primary thunderclap headache may be assigned.

(2) Worsening headache pattern. A worsening headache pattern must be interpreted in the context of a patient’s overall headache history. Headaches of recent onset may indicate a mass lesion, such as a brain tumor, abscess, or subdural hematoma. Although mass lesions often present with focal neurologic deficits or papilledema, these features may be absent, particularly if the mass lesion is slow-growing or in a silent area. In this context, neuroimaging is mandatory.

When progression occurs in the context of a well established primary disorder, 2 possibilities exist. Progression may represent the development of a new headache disorder (either primary or secondary) superimposed on a preexisting primary headache. Alternatively, progression may represent the transformation of a primary preexisting headache disorder. If these possibilities cannot be differentiated clinically, investigation is necessary.

Migraine and tension-type headache are well known to progress. Migraine may evolve to a condition known as chronic migraine, in which headache attacks (not necessarily migraine attacks) occur 15 or more days per month (or 180 or more days per year) with an average duration of 4 or more hours per day. Subjects with chronic migraine usually report a process of transformation over months or years, characterized by increasing headache frequency. Up to 80% of patients seen in specialty headache centers have this condition (Silberstein et al 2008).

Risk factors for the development of chronic migraine include high frequency of headaches prior to transformation, obesity, stressful life events, alcohol overuse, hypothyroidism, viral infections, head trauma, snoring, and sleep disturbances. Overusing acute medications is the most important risk factor for chronic migraine; it is present in more than 80% of chronic migraine patients in subspecialty clinics (Dodick 2009).

A gradual progression of headache in a migraine sufferer who has readily identified exacerbating factors (medication overuse) and a normal examination is most likely chronic migraine. Patients who have atypical clinical features or exacerbating factors that cannot be easily identified require neuroimaging.

(3) Headache with systemic illness or systemic symptoms. Many systemic disorders are associated with a prominent complaint of acute headache, including intracranial and extracranial infections (meningitis, encephalitis, Lyme disease, HIV, sinusitis), hypoxia and hypercapnia (high-altitude illness, diving, sleep apnea), dialysis, uncontrolled arterial hypertension, hypotension, hypothyroidism, fasting, collagen vascular disorder, systemic arteritis, and carbon monoxide poisoning, among others (Gladstone and Bigal 2008).

Clues that the headache is associated with a systemic illness include systemic symptoms, such as fever, neck stiffness, cutaneous rash, fatigue, malaise, and arthralgias. A skin rash could suggest Lyme disease (erythema migrans), herpes zoster (vesicles distributed in a dermatomal pattern), or sarcoidosis (erythema nodosum). Other dermatologic disorders might suggest the presence of a systemic or localized disease, such as antiphospholipid antibody syndrome or Sneddon syndrome (De Luca and Bartleson 2010). A clinician should search for opportunistic infections (including toxoplasmosis and cryptococcal meningitis) and malignancy in patients who have AIDS or HIV risk factors (Gladstone and Bigal 2010).

When patients have cancer, brain and leptomeningeal metastasis should be considered. Depending on the clinical setting, blood work, neuroimaging, and CSF examination are required.

(4) Headache with focal signs other than typical visual or sensory aura. Aura is most commonly associated with migraine, but also may occur with other primary headaches (chronic paroxysmal hemicrania, cluster headache, and tension-type headache) (Matharu and Goadsby 2001; Peres et al 2002; Krymchantowski 2005; Peres and Vieira 2006; Ekbom et al 2009). Typical migraine aura is rarely associated with secondary causes.

Focal signs other than aura are divided into those that are transient and those that are permanent. Transient focal signs may be the manifestations of seizure, transient ischemic attack, and toxic-metabolic disorders. Permanent deficits (even those that are partial and difficult to detect unequivocally) may be caused by stroke, mass lesion, arteriovenous malformation, or collagen vascular disease. Appropriate workup includes neuroimaging, collagen vascular evaluation, and sometimes lumbar puncture.

Differentiating a headache aura from a simple partial seizure may be difficult. Table 3 describes clinical clues that are useful in establishing this differentiation. If seizure is suspected, EEG, followed by neuroimaging (in subjects who have not been previously investigated), is required. Postictal headaches might be of special importance, especially considering that migraine and epilepsy are comorbid (Bigal et al 2003).

Table 3. The Aura in Migraine and Epilepsy

Symptom

Migraine

Epilepsy

 

Duration of aura

15 to 60 minutes

Brief, often--shorter than 1 min

 

Automatisms

Unusual

Frequent for complex partial seizures

 

Gastrointestinal aura

Abdominal pain (rare);

Nausea (common)

"Butterflies"--rising epigastric sensation

 

Visual disturbances

Positive or negative

Complicated visual phenomenon

 

Paresthesias

Common (5 to 60 minutes)

Common (seconds to minutes)

 

Altered consciousness

Usually responsive

Often unresponsive

 

Olfactory

Very uncommon

More common

 

Aphasia

Common

Common

 

Déjà vu

Rare

Common

Modified from: (Bigal et al 2003)

Headache triggered by cough, exertion, or orgasm. The key issue in establishing this red flag is to identify the sudden development of a severe headache temporally related to a trigger. In other words, severe headache unequivocally triggered by cough, heavy exercise, or orgasm must be investigated. Postcoital headaches, mild headaches following exercise, and mild headaches followed by cough do not seem to be associated with secondary headaches at a higher risk than headaches not associated with red flags.

A headache triggered by straining, coughing, or sneezing suggests a hindbrain malformation, occipitocervical junction disorder (including Arnold-Chiari malformation), increased intracranial pressure, or vasospasm. With orgasmic headaches, one must exclude subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, and mass lesions (Wang and Fu 2010).

Headache during pregnancy or postpartum. Most headaches that occur during pregnancy or postpartum are migraine or tension-type headaches. In a pregnant or postpartum woman with a history of migraine or tension-type headache, without atypical features and with a normal examination, investigation is usually not necessary. However, some women report new onset of severe headaches with migraine features, or a worsening pattern of a previously diagnosed primary headache. In these cases, cortical vein or cranial sinus thrombosis, carotid dissection, and pituitary apoplexy enter into the differential diagnosis. These disorders are much more common in the third trimester or in the early postpartum period. Stroke is thought to be more common in late pregnancy and the early postpartum period. Neuroimaging, including MRI and MRA, is necessary to exclude such vascular disorders. The differential diagnosis also includes preeclampsia, a multi-system disorder with various forms. In addition to hypertension and proteinuria, tissue edema, thrombocytopenia, and abnormalities in liver function can occur. Preeclampsia appears to involve a strong maternal inflammatory response with broad systemic activity. Subsidiary investigation includes blood and urine testing (Loder et al 2006; Contag et al 2009).

Positional headaches. Orthostatic and reverse-orthostatic headaches bring to mind dysregulation of cerebrospinal fluid pressure/volume. Though orthostatic headaches are typically due to low pressure/volume, and reverse-orthostatic headaches can be due to elevated pressure/volume, the opposite may also be true. In fact, elevated pressure/volume usually does not present with positional headaches, but rather with visual changes, pulsatile tinnitus, and papilledema, with variable headache quality (Friedman et al 2008). The diagnosis of a low pressure/volume state is suggested not only by orthostatic headache, but also by “second-half-of-the-day headache.” Migraine features are common, and if significant hindbrain descent occurs, cerebellar and brainstem signs and symptoms may be present. MRI with gadolinium may show “brain sag,” pituitary engorgement, and pachymeningeal enhancement, and MRV may show the “venous distention sign” of a convex appearance to the transverse sinuses on sagittal view (Agid et al 2008; Mokri 2013). Some orthostatic headaches are due to slow, undetectable leaks or result from increased compliance of the lower lumbar CSF space without actual leak (Leep Hunderfund and Mokri 2008). Other orthostatic headaches are not due to CSF pressure dysregulation at all, but rather to autonomic dysfunction in disorders such as orthostatic hypotension and postural orthostatic tachycardia syndrome (Lanier et al 2011). Finally, orthostatic headache may also be reflective of vestibular pathology, particularly in the presence of vertigo, nystagmus, and other positional triggers.

Headache in the elderly. Headache in this age group should always be investigated for secondary cause, although primary headaches do occur. Giant cell arteritis is an underdiagnosed and preventable cause of visual loss in the elderly. When giant cell arteritis is suspected (headache, constitutional signs and symptoms, jaw claudication, temporal artery tenderness) and the erythrocyte sedimentation rate is elevated, empiric treatment with steroids is justified while awaiting the results of a biopsy of the temporal artery. The workup must be guided by the clinical picture, but often includes a complete blood cell count with differentiation, sedimentation rate, and chemical profile (Nahas 2012). Headache in the elderly associated with activity may be an anginal equivalent, a rare disorder sometimes termed “cardiac cephalgia” (Bini et al 2009). Other common diagnostic considerations are cervicogenic headache from severe degenerative disease, metastatic cancer, and subdural hemorrhage; these are usually suggested by typical history and examination findings. A common primary headache disorder in the elderly is hypnic headache (see below).

Sinus symptoms and headache. Congestion, rhinorrhea, aural fullness, and facial pain may occur in primary headache disorders (migraine, tension-type, and cluster headaches), often leading to a misdiagnosis of “sinus headaches.” In one series, only 5% of suspected sinus headaches actually met criteria for this diagnosis (acute sinus infection with headache that resolves after appropriate antimicrobial therapy), leading to incorrect treatment with antibiotics in a vast majority, sinus endoscopy in about a quarter, and even septoplasty in about 15% (Foroughipour et al 2011). A diagnosis that is not to be missed is sphenoid sinusitis, an elusive entity due to the general lack of obvious sinus symptoms. Fever and facial numbness are 2 key features suggesting the disorder, which are easily seen on neuroimaging. Undiagnosed, it can lead to significant morbidity.

In This Article

Introduction
Overview
Approaching a patient with acute headache
Identifying secondary headaches
Diagnosing a primary headache disorder
Low-to-moderate frequency headaches of long duration
High-frequency headaches of long duration
Headaches of shorter duration
Conclusions
References cited
Contributors