Differential diagnosis of headaches

Dr. Justas Simonavičius Prepared according to Hainer BL, Matheson EM. Approach to acute headache in adults. Am Fam Physician. 2013 May 15;87(10):682-7.

Introduction Headache afflicts many people. The main task for a family physician evaluating a patient complaining of headaches is to determine whether the headache is benign or possibly caused by a neurologic or systemic condition that poses a threat to health and life. The most common form of headache in clinical practice is tension-type headache, affecting up to 40% of the world's population.

Migraine affects about 10% of people, while cluster headache is experienced by 1% of the population (1, 2). The most common diagnosis is made by evaluating the patient's medical history (3). The International Headache Society published a headache classification and diagnostic criteria back in 2004 (4).

Headache Classification

This classification is used in epidemiological and clinical studies. In clinical practice, it is useful to classify headaches into primary (tension, cluster, migraine headache) and secondary (caused by infectious, vascular, or other diseases).

Practical Application

This classification allows the physician to categorize patients into two groups. First are those whose headaches, although causing short-term health disturbances and a decrease in quality of life, do not present threatening consequences to health or life. Second are those for whom the headache is caused by a systemic or neurologic condition, requiring a different investigative and treatment strategy (Table 1).

Primary Headache

If a patient complaining of headaches does not exhibit symptoms or signs typical of secondary headaches, the risk of a serious underlying condition causing the headache is low. Nevertheless, the headache experienced by this patient should exhibit characteristics typical of primary headaches (Tables 1–5) (4, 5). The criteria for low-risk headaches are presented in Table 6 (6). In cases of low probability of headaches caused by serious conditions, additional imaging studies are not necessary (7).

Table 1. International Headache Classification

Primary Headache

Migraine

Tension-type headache

Cluster headache

Others (e.g., cold-induced headache)

Secondary Headache

•    Headache related to head or neck trauma, head or neck vascular pathology, nonvascular intracranial pathology, medication or substance use or withdrawal, infections, homeostatic disturbances, mental disorders

•    Head or facial pain caused by head, neck, eye, ear, nose, sinus, dental, oral, or other facial and (or) skull structure pathology

Tension-Type Headache Tension-type headache is the most common headache in clinical practice, affecting more than 40% of people worldwide (1). This pain is characterized by mild to moderate bilateral pressure without other symptoms (4). Tension-type headache slightly more commonly affects women than men (8).

It is believed that this pain arises from pain receptors in the pericranial myofascial tissues (9, 10). Scientific studies have found that individuals experiencing chronic tension-type headaches have increased sensitivity in pericranial myofascial tissue to pressure, electrical, or heat stimuli.

Moreover, it has been observed that these individuals can feel pain even with a normal, non-threatening stimulus (10–12). If a patient complaining of tension-type headaches symptoms, after performing neurological clinical examinations, no pathological signs are found, further laboratory or instrumental examination is not necessary (13). The diagnostic criteria for tension-type headaches are presented in Table 2 (5). Table 2. Diagnostic criteria for infrequent episodic tension-type headaches

Infrequent episodic tension-type headache

Headache occurring less than 12 times a year and less than once a month (total of at least 10 episodes), characterized by: • Headache can last from 30 minutes to 7 days. • The presentation includes at least 2 of these features: bilateral location, pressing or tightening (non-pulsating) quality, mild or moderate intensity, and no aggravation from routine physical activity such as climbing stairs or walking on level ground. • There is an absence of nausea or vomiting, but photophobia or phonophobia may be present. • Pain not caused by another disorder or condition

Frequent episodic headache

Headache occurring for more than 3 months, more than 1 day but less than 15 days per month (at least 10 episodes), with the same characteristics as infrequent episodic tension-type headaches (see above)

Migraine Distinguishing migraine from tension-type headaches is often aided by typical migraine symptoms such as nausea, photophobia (increased sensitivity to light stimuli), or phonophobia (increased sensitivity to sound stimuli). Physical activity often exacerbates the intensity of migraine headaches.

In the diagnosis of migraines, a comprehensive assessment of all symptoms and signs plays a significant role. If at least 4 of these features are present (pulsating pain, duration of pain from 4 to 72 hours, unilateral localization, nausea or vomiting, high intensity of pain), the diagnosis of migraine is highly probable (14, 15). Some migraine patients experience an aura.

Auras involve various visual, sensory, and speech disturbances that develop gradually, last no longer than 60 minutes, and resolve spontaneously. The criteria for migraines with aura (Table 3) and migraines without aura (Table 4) are presented separately. Table 3. Diagnostic criteria for migraines with aura

At least 2 episodes with the following features

• Aura, characterized by at least one of these symptoms, but without motor disturbances: transient fully reversible visual disturbances (flashes, dots, lines, shimmering lights, blind spots in the visual field, or vision loss), transient sensory disturbances (tingling, crawling sensation, numbness or decreased sensation, speech disturbances)

• At least 2 of these features: homonymous visual disturbances and/or unilateral symptoms; at least 1 aura symptom gradually progressing over 5 or more minutes or several aura symptoms occurring one after the other over 5 or more minutes; aura symptoms last at least 5 minutes but no longer than 60 minutes

• Migraine-type headache (Table 4), which starts either during the aura or immediately after the aura ends, but not later than 60 minutes after the onset of the aura

Table 4. Diagnostic criteria for migraines without aura

Cluster Headache Cluster headache is diagnosed relatively rarely. It is characterized by sudden onset episodes of very high-intensity headaches lasting 15-180 minutes, accompanied by symptoms typical of autonomic nervous system dysfunction (Table 5) (1, 4).Although cluster headaches are diagnosed much less frequently than tension-type headaches or migraines, it is estimated that about half a million people in the United States experience this condition at least once in their lifetime (16). Cluster headache episodes can occur in patients of various ages, but it has been observed that about 70% of cases develop before the age of 30 (17). Patients often describe cluster headaches as sharp, but they can also have a pulsating or pressing quality.

While cluster headaches can be bilateral, they are more commonly unilateral. The pain usually occurs behind the eye, less frequently in the temple, upper or lower jaw, teeth, forehead, or neck areas. Typically, the pain starts on one side of the body, while autonomic nervous system dysfunction symptoms appear on the other side (e.g., eyelid swelling, nasal congestion, tearing, sweating on the forehead). These episodes can repeat several times a day (up to 8 episodes) and last 15-180 minutes (4). The most common form of cluster headache is episodic cluster headache. It affects about 80-90% of all patients with the condition. With this form of the disease, episodes recur daily for several weeks, then the pain attacks stop, and a period of improvement begins (4). Episodes of cluster headaches typically recur every 3 to 12 weeks, and the improvement phase lasts about 12 months, after which the headache attacks recur. If a person has a chronic form of the condition (10-20% of all patients), the pain attacks occur continuously, with no significant improvement periods (4). Cluster headaches are often diagnosed late. It has been found that only 25% of patients with cluster headaches receive a correct diagnosis within the first year of symptom onset (16). Furthermore, even 40% of all patients with the condition do not receive a correct diagnosis within the first 5 years (16). Instead of cluster headaches, migraines are most commonly misdiagnosed (34%), followed by sinusitis (21%), and allergic diseases (6%) (15). Family history may also play a role in the significance of the disease. Patients with cluster headaches often have other chronic conditions, such as depression (24%), sleep apnea (14%), restless legs syndrome (11%), asthma (9%) (15). In recent years, more attention has been paid to the importance of treating depression in managing cluster headaches, as most individuals with this condition admit to occasionally having suicidal thoughts; about 2% of patients with cluster headaches have attempted suicide at least once (16, 18, 19). Table 5. Diagnostic criteria for cluster-like headache

At least 5 episodes with the following characteristics

• Severe or very severe unilateral pain behind the eye, above the eye socket, or in the temple area, untreated lasting from 15 to 180 minutes. • Associated with the headache, there is at least 1 symptom of autonomic nervous system dysfunction on the side opposite the pain. These symptoms may include conjunctival injection or tearing, nasal congestion or rhinorrhea, eyelid edema, facial sweating, ptosis, miosis, restlessness, or agitation. • Headache episodes can recur with varying frequencies, ranging from one episode every other day to as many as 8 episodes per day. • The headache is not caused by any other underlying condition.

Episodic Cluster Headache

• All the listed characteristics of cluster headache are present. • There must be at least 2 cluster headache periods that last from 7 to 365 days. Additionally, there should be at least one month-long period during which headache episodes do not recur.

Chronic Cluster Headache

• All the above characteristics of cluster headache are present. • Cluster headache episodes recur for over a year without improvements lasting longer than one month.

Threatening Headache Distinguishing a threatening headache to health and life from benign (low-risk) pain is not easy, therefore the differential diagnosis poses many challenges for practicing physicians. Certain clinical situations summarized in Table 7 are useful in differentiating the causes of headaches (5, 20–24). The signs and symptoms of a threatening headache were identified through retrospective analyses of clinical studies and expert consensus. Therefore, these signs are not very precise in determining the cause of a threatening headache. If a patient is experiencing symptoms characteristic of secondary headache, the treating physician must carefully assess the risk. In the case of acute head trauma, a computed tomography scan of the brain is usually used, as it is readily available, quickly performed, and accurate.

However, the sensitivity of magnetic resonance imaging of the brain in detecting bleeding under the dura mater and small-volume brain lesions is higher (20). Table 6. Criteria for Low-Risk Headache

• Patient is younger than 30 years old. • Characteristics typical of primary headache are evident (Tables 1–5). • The patient has experienced previous episodes of similar headaches. • Neurological examination reveals no pathological changes. • The nature of the previous pain remains unchanged. • Chronic illnesses, such as human immunodeficiency virus infection, are absent. • The medical history and clinical examination show no suspicious details (Table 7).

Table 7. Examination of a Patient Complaining of Acute Headache: Signs and Symptoms of Threatening Conditions

Symptom or Sign	Possible Diagnosis	Further Examination
First-time or such intense headache	Central nervous system infection, bleeding into the brain	Imaging studies
Focal neurological symptoms (atypical for typical aura)	Arteriovenous malformation, collagen defect-related vascular brain damage, intracranial processes	Blood and imaging studies
When coughing, engaging in physical activity, or during sexual intercourse, headaches intensify	Volume processes, subarachnoid hemorrhage	Spinal canal puncture, imaging studies
Headache accompanied by personality changes, mental or consciousness disorders	Central nervous system infection, bleeding into the brain, volume processes	Blood tests, spinal canal puncture, imaging studies
Neck stiffness or meningism	Meningitis	Spinal canal puncture
New-onset high-intensity headache during pregnancy or after childbirth	Venous/sinus thrombosis, vertebral artery dissection, pituitary insufficiency	Imaging studies
Age >50 years	Volume processes, temporal arteritis	Inflammatory markers, imaging studies
Optic disc edema	Encephalitis, volume processes, meningitis	Spinal canal puncture, imaging studies
Suddenly appearing and rapidly progressing headache during physical activity	Vertebral artery dissection, bleeding into the brain	Imaging studies
Suddenly onset and reaching maximum intensity within a few seconds or minutes headache	Bleeding into the brain, arteriovenous malformation, volume processes, subarachnoid hemorrhage	Spinal canal puncture, imaging studies
Headache accompanied by systemic disease symptoms (fever, rashes)	Arteritis, vascular pathology due to collagen defects, encephalitis, meningitis	Blood tests, spinal canal puncture, imaging studies, skin biopsy
Tenderness over the temporal artery	Polymyalgia rheumatica, temporal arteritis	Inflammatory markers, temporal artery biopsy
Intensifying headache	Medication use and overdose, volume processes, bleeding under the dura mater	Imaging studies
Headache of changing nature experienced by patients with: cancer HIV infection Lyme disease	Metastases Infection, tumor Meningoencephalitis	Spinal canal puncture, imaging studies in all cases

Medical History and Patient Examination

Headache that suddenly starts and reaches intensity within a few minutes should be taken quite seriously. A rapid examination of the patient plays a crucial role in this clinical situation. Such pain is characteristic of subarachnoid hemorrhage, hypertensive crisis, vertebral artery dissection, acute angle-closure glaucoma, and others.

Risk Factors for Headache

The use of psychoactive substances, such as cocaine or methamphetamine, can increase the risk of bleeding into the brain and stroke. Additionally, certain over-the-counter or prescription medications, such as aspirin, nonsteroidal anti-inflammatory drugs, anticoagulants, and glucocorticoids, also raise the risk of bleeding into the brain.

Immune System Deficiency and Headache

If a person with human immunodeficiency virus infection or other immune system deficiencies complains of a headache, the cause of the pain may be a brain abscess, meningitis, or a tumor of the central nervous system (CNS). An infectious process in the CNS can spread from the lungs, sinuses, or eyes.

Severe Headache Evaluation

Patients who claim that their headache is the worst they have ever experienced should be carefully evaluated, especially if they are over 50 years old or if the pain worsens with physical activity (including sexual activity). These signs suggest that the patient may have experienced acute bleeding into the brain or vertebral artery dissection.

Accompanying Neurological Symptoms

Patients with headaches accompanied by neurological symptoms such as altered consciousness, seizures, or visual disturbances should be evaluated urgently. Symptoms characteristic of serious causes of headaches are presented in Table 7 (5, 20–24). The likelihood of CNS damage greatly increases with objective neurological symptoms (6, 14, 27).

Migraine and Aura

Migraine may be accompanied by focal neurological symptoms. However, if these symptoms occur for the first time in a person's life, they should be considered signs of a potentially serious condition. According to the definition of migraine with aura, the aura lasts no longer than 60 minutes. Therefore, in all cases where aura-like symptoms persist longer than 60 minutes, urgent patient evaluation is necessary.

Clinical Examination Findings

During clinical examinations, both very strong symptoms and signs, such as meningeal signs or loss of vision in one eye, as well as subtle changes, such as decreased peripheral reflexes, can be identified. Moreover, altered consciousness and psychomotor agitation are characteristic of serious CNS diseases.

Additional Considerations

Additionally, if fever, optic disc edema, or severe hypertension (systolic blood pressure (SBP) greater than 180 mm Hg or diastolic blood pressure greater than 120 mm Hg) occur along with a headache, CNS infection and other conditions that increase pressure within the skull should be ruled out.

Hypertension and Head Injuries

In the presence of hypertension, it is important to assess whether SBP can be safely reduced to prevent hypertension-related bleeding into the brain. Moreover, bruising and head injuries increase the likelihood of bleeding into the brain (Table 7) (5, 20–24).

Instrumental and laboratory diagnostics

Imaging studies CNS imaging should be performed on all patients presenting with signs and symptoms of severe headache, as these patients have a high risk of organic brain disease. Although there is still debate today on how an emergency patient complaining of severe headache should be evaluated, the American College of Radiology has published several practical recommendations (Table 8) (28). Table 8. Evaluation of a patient complaining of headache using imaging methods (Recommendations of the American College of Radiology)

Clinical Signs	Recommended Study
Headache in a patient with compromised immune system	Head MRI with and without contrast
Headache in a person over 60 years old with suspected temporal arteritis	Head MRI with and without contrast
Headache suspected of meningitis	Head CT or MRI without contrast
Intense headache during pregnancy	Head CT or MRI without contrast
Severe, unilateral headache when suspected vertebral artery or other artery dissection	Head MRA with and without contrast, head and neck MRA or head and neck CTA
Very severe or unusually sudden onset headache; the worst headache ever experienced by the patient	Head CT without contrast; head CTA with contrast, head MRA with or without contrast, or head MRA without contrast

CT – computed tomography, CTA – computed tomography angiography, MRI – magnetic resonance imaging, MRA – magnetic resonance angiography.

Lumbar Puncture

Publication "Internistas" No. 1, 2018