Clinical Pearls in Management of Headache

Introduction

Headache, an almost universal human experience, is one of the most common complaints encountered in general medical practice. The assessment of this condition may be uncomplicated or difficult, and, though often benign, headache may prove to be a worrying symptom. This review discusses clinical pearls of in various headache disorders commonly encountered in daily practice.

The International Headache Society has published a system of classification and operational diagnostic criteria for headache based on clinical consensus.1 Classifying headaches into primary and secondary types is useful to differentiate headaches that have no dangerous underlying cause from those that may be a sign of significant pathology, because they represent an underlying systemic or neurologic disorder.

Secondary Headache Disorders²

The index of suspicion for a secondary cause of headache can be effectively raised by identifying historical and examination red flags.

The acronym SNOOP4 (“snoop for” red flags) may be useful as a memory aid to ensure that warning signals for sinister causes of headache that are associated with serious morbidity and mortality are not overlooked.

Table 1: Warning Signals to Raise Suspicion of Secondary Causes of Headache Using the Mnemonic SNOOP4²

If papilloedema present: consider idiopathic increased intracranial hypertension.

Clinical Pearls

1. The SNOOP4 acronym is a useful guide to assist clinicians in systematically evaluating for warning symptoms and signs of a secondary cause of headache.
2. Since secondary causes of headache often have features that resemble migraine, tension-type headache, or a trigeminal autonomic cephalalgia, caution must be exercised, and warning signs and symptoms of secondary headache must be evaluated.
3. A headache history is the most important aspect of the evaluation of a patient presenting with headache and eliciting worrisome features with directed questioning is necessary. The history must be taken without assuming that key features will be volunteered by the patient.
4. Brain tumors constitute a rare cause of headache and even less frequently present with severe pain. Approximately 30% of patients diagnosed with a brain tumor report headache on presentation; BUT, only 1% to 2% report headache as the sole clinical symptom.
5. Reversible cerebral vasoconstriction syndrome headaches are often bilateral, brief in duration (1 to 3 hours), recurrent over a span of days to 4 weeks, and are sudden in onset, rapidly reaching a maximal severe intensity (thunderclap).
6. The occurrence of cranial autonomic symptoms in migraine (such as lacrimation, nasal congestion, and rhinorrhea) may contribute to the misdiagnosis of “sinus headache.”
7. Headache attributed to temporomandibular disorders is usually unilateral and should be ipsilateral to the pathology when the temporomandibular complex is the source of pain, but can be bilateral when muscular involvement is present.

Headache Red flags

(a) Clinical red flag

• Sudden severe headache
• Worsening of pre-existing headache
• New headache in pregnancy or post-partum
• Headache worse in the morning
• Headache worse with neck flexion/extension
• Headache worse in the upright posture
• Headache at the occipito-cervical junction
• Cluster type headaches
• Undefined headaches
• Posttraumatic onset

(b) Triggers red flag

• Cough
• Exertion
• Orgasm
• Valsalva manoeuvre- induced

(c) Associated red flag

• Onset of headache after age 55 years
• Systemic symptoms
• Systemic diseases
• Focal signs not typical of aura
• Papilledema
• Painkiller overuse
• New drug use at onset of headache
• Immunosuppression e.g., HIV
• Previous cancer
• Pregnancy or puerperium

Primary headache disorders

The three major and most common primary headache disorders are migraine, tension-type headache (TTH), and trigeminal autonomic cephalalgias (TACs).

TTH is the most common primary headache disorder in the general population, BUT migraine is overwhelmingly the most common primary headache disorder presenting at GP clinics.³

Tension-type headache (TTH)^4,5

This is the most common type, with a lifetime prevalence in the general population of up to 80%. There is often a degree of associated disability, and this, combined with the high frequency, produces significant socioeconomic impact.

Clinical Pearls

1. In those patients with chronic daily headache having features of both tension-type headache and migraine, treatment may prioritize to the preventive management of migraine.
2. The head muscles that are most likely to tighten and cause a muscle tension headache. It can be affected by physical stress or emotional stress.
3. A headache at the front of the head need not originate there. A tense trapezius muscle sets off a chain reaction, other muscle to tense and producing pain in the forehead.
4. Pericranial tenderness can be present in the following muscles

• Frontalis
• Temporalis
• Lateral and medial pterygoid
• Masseter
• Sternocleidomastoid
• Trapezius

Fig 1: Location of pericranial muscles to palpate for tenderness

Migraines

The main subtypes are migraine with and without aura. An aura is a fully reversible set of nervous system symptoms, most often visual or sensory symptoms, typically develops gradually, recedes, and is then followed by headache accompanied by nausea, vomiting, photophobia, and phonophobia. Less common symptoms of aura include speech/ language symptoms, motor or brainstem symptoms, or retinal symptoms. If an aura contains multiple features, symptoms usually occur in succession of at least 5 or so minutes each, with a total symptom complex of 5-60 minutes.

The headache in migraine is typically described as unilateral (approximately 60%) and of moderate to severe intensity.

An individual’s headache attacks tend to be mostly stereotyped; many variations can be present.

The headache may be followed by a postdrome, characterized by impaired concentration and feelings of fatigue, or feeling “washed out.”6 The postdrome can last for 24 to 48 hours after resolution of the headache. People with migraine report cognitive, autonomic, and sensory symptoms between their migraine attacks.

Clinical Pearls ^7,8

1. The overwhelming majority (94%) of patients presenting with recurrent primary headaches as a chief complaint in clinical practice have migraine.
2. The goals of acute migraine treatment are to treat attacks quickly and consistently, prevent recurrence, and restore the patient to functionality
3. Triptans, paracetamol, aspirin, ibuprofen, naproxen, and diclofenac sodium have Level A evidence for the acute treatment of migraine.
4. A nonoral route for migraine medication is preferred in patients with nausea or vomiting or rapid-onset attacks.
5. Stratified care (as oppose to step by step care) is best for patients with multiple types of migraine attacks.
6. Treatment early in the course of the attack produces the best results. Features of the headache, including severity, speed of onset, and early associated nausea/vomiting, may influence the choice of agent(s).
7. Triptans are considered first-line treatment for moderate to severe migraine attacks.
8. Triptans are contraindicated in people with vascular disease.
9. Preventative medication is recommended if the patient is suffering from headaches more than 6 days, impaired for 4 days, or completely disabled for 3 days each month despite abortive treatment.
10. Preventive treatment reduces migraine-related disability over and above the associated reduction in attack frequency.
11. Oral preventive treatments with good evidence include sodium valproate, topiramate, propranolol, metoprolol, amitriptyline, venlafaxine and second line groups include lisinopril, candesartan, gabapentin, pregabalin, and zonisamide.
12. Oral medication choice depends on effectiveness, side effect profile, contraindications, and patient preference.

Status Migrainosus⁹

It is a debilitating migraine attack lasting for more than 72 hours. It is not a true complication of migraine but rather a migraine headache that is beyond spontaneous resolution. Aims of the treatment for status migrainosus are:

• Rehydration
• Pain control, and
• Reversal of continuous headache

Clinical Pearls

1. Although, strictly defined, status migrainosus is a migraine headache lasting >72 hours, treatment often needs to start earlier if associated with significant uncontrolled vomiting and/or dehydration.
2. Oral Treatment of Status Migrainosus

A. Sumatriptan 100 mg + Naproxen Sodium (400 mg)/Ibuprofen 400 mg (with a H2 blocker or a PPI)

B. Metoclopramide (10 mg) + Diphenhydramine (25 mg) +Ibuprofen (400-800 mg)

C. Prednisone 60 mg oral for 1-2 days and rapid taper over 7 to 14 days (with a H2 blocker or a PPI)

D. Dexamethasone 4-8 mg oral for 1-2 days and rapid taper over 5 to 7 days (with a H2 blocker or a PPI)

3. In-Clinic Rescue Therapies: Initial Steps

Step 1: Start an IV and hydrate (use NS, Ringer lactate), 250-500 cc, rapid hydration)

Step 2: Initial Treatment

• Prochlorperazine 10 mg ±Diphenhydramine 25 mg ±
  Dexamethasone 10 mg IV (Methylprednisolone 500 to 1000 mg) ±
  Ketorolac 30 mg IM/IV
• (if available Sumatriptan 6 mg SQ or Dihydroergotamine-
  DHE 0.5-1 mg IV can be used)
  Step 3: Second line options
• Prochlorperazine 10 mg IV
• Paracetamol 1 gram IV
• Magnesium 500-1000 mg IV (can go up to 2000 mg if there is significant t aura with status migrainosus)
• Ondansetron 4 mg IV
• Oxygen 100% 12 to 15 liters using NRB
• Levetiracetam 500-1500 mg IV (if there is signiicant aura present)
• Divalproex 500-1000 mg IV (if available)

Trigeminal Autonomic Cephalgias (TACs)^10,11,12

It is a group of headache disorders present as unilateral trigeminal distribution pain attacks, often associated with ipsilateral cranial autonomic features.

Autonomic Features of TACs are (1) Conjunctival injection, (2) Lacrimation, (3) Nasal congestion or discharge, (4) Miosis and (5) Ptosis.

(1) Cluster headache, (2) paroxysmal hemicrania, (3) short-lasting unilateral neuralgiform headache attack (SUNHA) syndromes, and (4) hemicrania continua are all grouped as TACs.

The TACs share some similarity with migraine phenotype, pathophysiology, and therapy but represent a distinct set of syndromes requiring different management.

The pain of TACs tends to be relatively short and intense, is accompanied by symptoms reflective of autonomic dysfunction.

Its pathophysiology is likely linked to dysfunction of the hypothalamus, trigeminally mediated reflexes, and nociception.

Secondary causes of TACs often involve pathology affecting the trigeminal root, hypothalamus, pituitary gland, or cavernous sinus.

Clinical Pearls

1. 3A of TACs:

• Anteriorly located side-locked pain
• Autonomic features-ipsilaterally
• Agitation or restlessness

  2. Non-urgent MRI brain w/o contrast should be done to rule out lesions in or around the pituitary can mimic TACs
  3. Persistent INTER-ATTACK autonomic features require CTA brain and neck emergently
  4. TACs can mimic carotid dissection
  5. Cluster headache attacks must be addressed with rapid-onset therapies (e.g., inhaled or injected), and, since attacks can be frequent, toxicity from repeated treatments must be considered
  6. Corticosteroids (administered orally, via suboccipital injection, or, less commonly, intravenously) are very useful as transitional therapy in cluster headache
  7. Paroxysmal hemicrania is cluster like, with a female predominance, greater attack frequency, less periodicity, different triggers, and, above all else, exquisite response to indomethacin
  8. Indomethacin is most useful for paroxysmal hemicrania and hemicranias continua, requires proper titration, and monitoring
  9. If a chronic primary headache diagnosis is unclear, consider an indomethacin trial, particularly if there are no contraindications, and if cranial autonomic symptoms are present
  10. Short-lasting unilateral neuralgiform headache attacks are like V1 trigeminal neuralgia, with autonomic features and no refractory period to cutaneous triggering (when present); look for pituitary pathology and vascular loop compression in all cases

Side-locked headache¹³

Side-locked headache means headache always on the one side.

Strictly unilateral headaches account for almost 20% of headaches in subjects attending a headache clinic.

TACs in general (52%) and cluster headache in particular (38%) are the most frequent diagnoses, but secondary headaches account for 20% of the cases.

Strictly unilateral head pain is an essential feature of all trigeminal autonomic cephalalgias (TACs).

Table 2: Proportion of patients with Side-locked pain in different primary headache disorders

Table 3: Common secondary side locked headache

Fig 2: Provocative procedures to reproduce pain in various secondary headaches and neuralgia

Indomethacin-responsive headache syndromes¹⁴

Indomethacin-responsive headache syndromes represent a unique group of primary headache disorders characterized by a prompt and often complete response only to indomethacin exclusively. Because these headache disorders can easily be overlooked in clinical practice, they likely are more common than previously recognized.

Indomethacin-responsive headache syndromes can be divided into several distinct categories and each category can be differentiated clinically and by the extent to which the individual headache disorders respond to indomethacin.

Hemicranias

Paroxysmal hemicrania (PH)

Paroxysmal hemicrania (PH) like syndrome (with bilateral headaches and no autonomic features)

Hemicrania continua (HC)

Valsalva-induced headaches

Primary cough headache

Primary exertional headache

Primary headache with sexual activity

Sharp, short-lived head pain syndrome (SSHP) (aka ice pick headache)

Other indomethacin-responsive headaches

Primary stabbing headache

Hypnic headache

Nummular headache

Ophthalmoplegic migraine

Indomethacin treatment regime

1. Starting dose is 25mg TDS (response usually within 48 hours)
2. If no response, increase to 50mg TDS, maximum is 100 mg TDS
3. Indomethacin is contraindicated together with oral anticoagulants

Other Primary Headaches ^10,11,12

Fig 3: Overview of other primary headache disorders

Clinical Pearls

1. Clinical distinction must be made between headache that is triggered by a Valsalva maneuver (a red flag) and headache that is aggravated by a Valsalva maneuver (typical of migraine.
2. A history of cough-induced headache may indicate a posterior fossa lesion, most often a Chiari malformation type I. (75% of cough induced headache). Primary cough headache responds very well to treatment with indomethacin.
3. Primary exercise headache often has a short duration and generally does not have typical migraine features apart from a throbbing pain character.
4. Primary exercise headache is precipitated by sustained physically strenuous activity rather than short duration precipitating factors such as cough, Valsalva maneuver, or orgasm.
5. The high prevalence in athletes, it should be considered when evaluating an athlete with headache.
6. Precipitation of headache by exercise or exertion is a headache red flag and should raise concern for a secondary cause of headache.
7. Most of the primary exercise headache is a self-limited disorder in the majority of patients.
8. In older adults at risk for coronary artery disease, cardiac angina may present with an exertional headache (cardiac cephalalgia).
9. An explosive attack just before or with orgasmic a thunderclap headache, which is a headache red flag and a neurologic emergency. Pretreatment 30 minutes prior to sexual activity with indomethacin can be an effective treatment for most patients with primary headache associated with sexual activity. If long term prevention is needed, beta-blockers have also been used successfully.
10. Patients with recurrent thunderclap headache (including headache associated with sexual activity) is caused by reversible cerebral vasoconstriction syndrome. Patients with a very irst presentation of thunderclap headache should irst be evaluated for subarachnoid hemorrhage.
11. Headache attributed to temporomandibular disorders is usually unilateral and should be ipsilateral to the pathology when the temporomandibular complex is the source of pain but can be bilateral when muscular involvement is present.

Miscellaneous Clinical Pearls ^12,15

1. For preventative migraine medical therapy, start with low doses of medication, particularly with antidepressants and other preventives.
2. Headache patients tend to be fairly somatic, and there is no need to push medicine very quickly.
3. In choosing preventives therapy for headache, look at comorbidities, particularly: anxiety, depression, insomnia, gastritis, gastroesophageal relux disease (GERD), blood sugar, constipation, hypertension, asthma, and sensitivities or allergies to other drugs. These often determine which way to proceed with medication.
4. Stick with preventive medications for at least four weeks (or longer). If physicians abandon them too soon, the beneicial effect may not be seen.
5. Weight gain is a major issue. Even though a drug may be more effective, choosing one that avoids weight gain (in those prone to it) is more likely to lead to long term success.
6. Fatigue is another major reason for patients abandoning a preventive medication. Headache patients commonly complain of fatigue. Many of our preventives (amitriptyline, beta blockers, valproate.) may add to weight gain and/or fatigue.
7. It is important to not miss a subarachnoid hemorrhage. Many patients with subarachnoid hemorrhage have had milder sentinel or warning headaches in the previous two weeks.
8. Rule out possible adverse effects caused by medications.
9. Advise patients to keep a headache diary.
10. Educate patients about common triggers such as not eating regularly, hypoglycemia, sexual intercourse, caffeine withdrawal (often on weekends), bright sunlight, tight ponytail holders, dehydration, and focal muscle tension (e.g., caused by extensive computer use, fear, sleeping positions, lifting weights) as well as food and substance triggers monosodium glutamate, tyramine, aspartame, alcohol, phenylethylamine, nitrates, and nitrites.
11. Encourage patients to do lifestyle modifications such as eating regularly, sleep in regular time, monitoring caffeine intake, wearing a hat and sunglasses when outdoors, or preparing their sleeping environment (e.g., choosing a comfortable pillow).
12. Being aware that there are cultural and ethnic differences in the perception and experience of headache can aid treatment.
13. Almost all patients should be on vitamin D, usually at least 1,000 units. Multivitamins have more negatives than positives for many patients, and the same is true for antioxidants. Vitamin D helps many conditions, among them pain and depression.
14. For depression to improve, it is important to control headache pain. Likewise, to help headache pain, depression must be treated.

References

1. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders. Cephalalgia. 2018; 38 (3rd edition):1-211.
2. Dodick DW. 2010 “Pearls: headache.” Semin Neurol; 30(1):74-81.
3. Stovner LJ, Hagen K, Jensen R, et al. 2007 “The global burden of headache: a documentation of headache prevalence and disability worldwide”. Cephalalgia; 27:193-210.
4. Langemark M, et al. 1988 “Clinical characterization of patients with chronic tension headache.” Headache;28(9):590-596.
5. Freitag F. 2013 “Managing and treating tension-type headache”. Med Clin N Am;97:281 292.
6. Burstein R, Noseda R, Borsook D. 2015 “Migraine: multiple processes, complex pathophysiology”. J Neurosci;35(17):6619-6629.
7. Lainez MJA. 2004 “Clinical benefits of early triptan therapy for migraine.” Cephalalgia; 24:24-30.
8. Rizzoli P. 2014 “Preventive pharmacotherapy in migraine”. Headache; 54:364-369.
9. Kabbouche M, Khoury CK. 2016 “Management of primary headache in the emergency department and inpatient headache unit”. Semin Neurol;23(1):40-43. doi:10.1016/j. spen.2015.08.004
10. Silberstein S, Lipton R, Dalessio D, et al., eds. 2008 “Wolf’s Headache and Other Head Pain”. Oxford: Oxford University Press.
11. Mathew PG, Garza I. 2011 “Headache”. Semin Neurol;31(1):5-17.
12. Evans RW, 2019 neurologic clinics Volume 37, Number 4 November
13. Prakash and Rathore, 2016 “Side locked headache”, The Journal of Headache and Pain 17:95-108
14. Zhu S, McGeeney B. 2015 “When indomethacin fails, additional treatment options for “Indomethacin responsive headaches.” Curr Pain Headache Rep;19(3):7. doi:10.1007/s11916-015-0475-2
15. Dodick DW. 2010 “Pearls: headache”. Semin Neurol; 30(1):74-81.

Author Information

Thar Thar Oo¹

M.B; B.S, M.D (USA), MPH, FAAN
Diplomate, American Board of Psychiatry and Neurology
Subspeciality diplomate in Vascular Neurology,
Headache and Facial Pain and Neuro-Toxicology
Senior Consultant Neurologist,
Asia Royal Hospital, Ar Yu International Hospital and
Grand Hantha International Hospital
Director, Clinical Neurology and Chief, Stroke Unit, Asia Royal Hospital