Headache and migraine symptoms, diagnosis and treatment

Headache and Migraine Diagnosis

The diagnostic approach to headache begins with a comprehensive patient history and neurological examination. For many primary headaches like typical migraine or tension-type headache, a diagnosis can often be made confidently based on the clinical presentation conforming to established diagnostic criteria (e.g., ICHD-3 criteria) [4]. Patients presenting with prolonged, chronic, or acutely severe headaches, or headaches with atypical features or associated neurological signs ("red flags"), warrant further investigation to rule out secondary causes, typically involving consultation with a neurologist or headache specialist.

Differential Diagnosis of Headache

Key elements of the diagnostic process include:

• Detailed Headache History: This is the most critical component. Use the characteristics described earlier (Quality, Location, Intensity, Onset, Duration, Frequency, Timing, Associated Symptoms, Aggravating/Relieving factors - often remembered by mnemonics like PQRST or SOCRATES). Also inquire about past headache history, response to previous treatments, family history of headaches (especially migraine), medication use (including over-the-counter drugs, supplements, caffeine), comorbidities (medical, psychiatric), sleep patterns, and lifestyle factors (stress, diet, exercise). Headache diaries kept prospectively are very valuable for tracking patterns and triggers.
• Neurological Examination: A thorough examination is essential primarily to screen for signs suggestive of a secondary cause ("red flags"). This includes assessment of mental status, cranial nerves (especially visual acuity, visual fields by confrontation, funduscopy for papilledema, pupillary reactions, eye movements), motor function (strength, tone, reflexes), sensation, coordination (finger-nose, heel-shin), and gait.
• Physical Examination: Includes vital signs (BP, temperature), examination of the head and neck for tenderness (palpation of pericranial muscles, sinuses, temporal arteries, TMJ, cervical spine range of motion and tenderness), auscultation for bruits (carotid, orbital), and examination relevant to suspected systemic causes.
• Identifying "Red Flags" (SNOOPP mnemonic is helpful): Certain features suggest a potentially serious underlying cause requiring urgent investigation (usually neuroimaging) [5]:
  • Systemic Symptoms (fever, weight loss, chills, myalgias) or Secondary Risk Factors (HIV, cancer, immunosuppression)
  • Neurologic Signs or Symptoms (focal deficits like weakness, numbness, diplopia; altered consciousness; papilledema; seizures)
  • Onset: Sudden, abrupt, or split-second ("thunderclap" headache)
  • Older Age: New onset or progressive headache after age 50 (risk of GCA, tumor, etc.)
  • Pattern Change: Significant change in frequency, severity, or clinical features of pre-existing headaches
  • Positional Worsening (suggests ICP changes), Precipitated by Valsalva/Exertion, Progressive headache despite treatment.
• Diagnostic Testing (Guided by history and exam findings, especially red flags):
• Neuroimaging: Brain MRI (with/without contrast) is generally preferred for evaluating non-acute headache with red flags due to higher sensitivity for most structural lesions (tumors, inflammation, prior infarcts, Chiari) and lack of radiation. Brain CT (non-contrast) is the first choice in acute/emergency settings to rapidly exclude hemorrhage (SAH, ICH, SDH), hydrocephalus, or large masses. Vascular imaging (MR Angiography/Venography, CT Angiography/Venography) is added if vascular pathology (aneurysm, dissection, vasculitis, CVT) is suspected. Cervical spine MRI may be needed for suspected cervicogenic headache or upper cervical pathology referring pain.
• Lumbar Puncture (LP) for CSF Analysis: Essential if meningitis, encephalitis, or SAH (with negative early CT) is suspected, or sometimes to measure opening pressure (for IIH or low CSF pressure). Must be performed only after neuroimaging has excluded a mass lesion or significant hydrocephalus that could cause herniation. Analysis includes opening pressure, cell count/differential, protein, glucose, Gram stain, cultures, and potentially specific tests (viral PCR, cytology, oligoclonal bands, etc.).
• Blood Tests: Guided by suspicion. Common tests include CBC, ESR, CRP (for infection/inflammation like GCA), basic metabolic panel, thyroid function tests. Specific tests for systemic diseases if indicated.
• Other Tests: Temporal artery biopsy (if GCA suspected). Ophthalmology consult for suspected ocular causes or papilledema. ENT consult for suspected sinus disease. Polysomnography for sleep apnea headache.

Brain magnetic resonance imaging (MRI) is indicated for headache evaluation when clinical features ("red flags") suggest a possible secondary cause, such as structural lesions, vascular abnormalities, or conditions causing abnormal intracranial pressure or hydrocephalus.

Important considerations in headache diagnosis:

1. Neuroimaging is generally not required for patients with a long history of stable headaches meeting clear diagnostic criteria for primary headache disorders like typical migraine or typical episodic TTH, especially if the neurological examination is normal [6]. Unnecessary imaging can be costly and may lead to anxiety over incidental findings (e.g., nonspecific white matter spots, pineal cysts) that are usually unrelated to the headache.
2. When imaging is indicated for headache evaluation, MRI (without and often with contrast) is generally preferred over CT for most non-acute situations due to its superior ability to detect a wider range of potential underlying pathologies (tumors, inflammation, ischemia, Chiari, pituitary issues, etc.). CT is faster and better for acute hemorrhage and bone detail.
3. Surgical procedures targeting supposed "migraine trigger points" (e.g., nerve decompression, muscle resection) are considered controversial and experimental by major headache societies and are generally not recommended as standard practice outside of clinical trials. Evidence-based pharmacological and non-pharmacological treatments should be prioritized [7].
4. Opioid and barbiturate-containing medications (e.g., codeine, oxycodone, hydrocodone, butalbital combinations) should generally be avoided or used very sparingly for the routine management of recurring primary headaches (like migraine or TTH) due to high risks of tolerance, dependence, addiction, worsening headache frequency, and development of medication-overuse headache (MOH) [8]. Their use should be limited to rare, specific rescue situations under careful supervision.
5. Frequent or prolonged use (e.g., >10-15 days/month depending on class) of any acute headache medication, including simple analgesics (paracetamol/acetaminophen, NSAIDs) and triptans, can lead to Medication-Overuse Headache (MOH), characterized by worsening headache frequency and development of chronic headache. Patients experiencing frequent headaches (>4 per month or debilitating attacks) should consult a physician for an accurate diagnosis and discussion of appropriate preventive strategies, rather than solely relying on escalating acute self-treatment [9].

The Management of Rare Trigeminal Autonomic Cephalalgias (TACs)

Trigeminal Autonomic Cephalalgias (TACs) are a group of primary headache disorders characterized by severe, strictly unilateral head pain localized in the trigeminal distribution (often orbital, supraorbital, or temporal), accompanied by mandatory ipsilateral cranial autonomic symptoms (such as conjunctival injection, tearing, nasal congestion, rhinorrhea, eyelid edema, forehead/facial sweating/flushing, miosis, ptosis, sensation of fullness in the ear) [1]. Differentiating between the TACs is crucial as treatment responses vary significantly, with some being exquisitely responsive to specific agents [10].

Key differentiating features based on attack duration, frequency, and response to indomethacin:

TAC Type (ICHD-3)	Typical Attack Characteristics	Key Differentiating Feature / Treatment Response
Cluster Headache (CH)	Duration: 15-180 minutes Frequency: 1 every other day to 8 per day Pain: Excruciating, boring/stabbing, orbital/temporal. Associated restlessness/agitation common during attacks. Autonomic features mandatory.	Longer duration attacks compared to other TACs (except HC). Often occurs in cyclical "clusters" (episodic CH) or continuously (chronic CH). Responds acutely to high-flow oxygen, subcutaneous/nasal sumatriptan. Preventive options: Verapamil (first-line), lithium, topiramate, galcanezumab.
Paroxysmal Hemicrania (PH)	Duration: 2-30 minutes Frequency: Usually ≥5 per day (often very frequent, >10-20/day) Pain: Severe, unilateral orbital/temporal/frontal. Autonomic features mandatory. Less agitation than CH.	Shorter, very frequent attacks compared to CH. Absolute and rapid response to therapeutic doses of indomethacin is pathognomonic/diagnostic [11].
Short-lasting Unilateral Neuralgiform headache attacks (SUN) - SUNCT - SUNA	Duration: 1-600 seconds (often very brief stabs, spikes, or saw-tooth pattern) Frequency: At least 1 attack/day up to hundreds per day (often very frequent bursts). Pain: Moderate/severe, stabbing/burning, orbital/temporal. Autonomic features mandatory. SUNCT: Both conjunctival injection AND tearing prominent. SUNA: Only one or neither of conjunctival injection/tearing. Other autonomic features may be present.	Very short (seconds), very frequent attacks; often triggered by cutaneous stimuli. Generally refractory to indomethacin and standard CH treatments. Lamotrigine often first-line preventive. Other options: topiramate, gabapentin, IV lidocaine (acute).
Hemicrania Continua (HC)	Continuous, moderate-intensity, strictly unilateral background headache present daily for >3 months. Superimposed exacerbations of severe pain occur, during which ipsilateral autonomic features +/- migraine-like features (nausea, photo/phonophobia) are present.	Presence of continuous background unilateral pain. Absolute and rapid response to therapeutic doses of indomethacin is pathognomonic/diagnostic [12].

Note: Neuroimaging (MRI Brain) is recommended for all suspected TACs, especially at first presentation, to rule out secondary causes (e.g., pituitary tumors, vascular lesions, posterior fossa pathology) that can mimic TAC phenomenology.

Understanding the presumed pathophysiology involving the trigeminovascular system activation, parasympathetic reflex activation (via the superior salivatory nucleus and sphenopalatine ganglion leading to autonomic symptoms), and potential central modulation/dysfunction (e.g., posterior hypothalamus implicated in cluster headache periodicity) helps guide targeted therapies [13].

Therapeutic approaches targeting different structures/mechanisms in TACs:

Potential Target / Mechanism	Example Therapy Options (Specific choice depends critically on TAC diagnosis)
Acute Attack Abortives	- Oxygen: High-flow (12-15 L/min) 100% oxygen via non-rebreather mask (First-line for Cluster Headache). - Triptans: Subcutaneous or nasal sumatriptan (Effective for Cluster Headache, less so for other TACs). - Lidocaine: Intranasal or IV (May help SUNCT/SUNA acutely). - Indomethacin: Oral or rectal (diagnostic/therapeutic for PH & HC, not effective for CH or SUNCT/SUNA).
Preventive Therapy - Channel Modulators	- Verapamil: Calcium channel blocker (First-line preventive for Cluster Headache, requires high doses & ECG monitoring). - Lamotrigine: Sodium channel blocker (Often first-line preventive for SUNCT/SUNA). - Topiramate: Multiple mechanisms including channel modulation (Preventive option for CH, PH, SUNCT/SUNA, HC). - Carbamazepine/Oxcarbazepine: Sodium channel blockers (May help SUNCT/SUNA). - Gabapentin/Pregabalin: Calcium channel modulators (May help SUNCT/SUNA, sometimes CH).
Preventive Therapy - Other Pharmacological	- Indomethacin: NSAID (First-line, diagnostic for Paroxysmal Hemicrania & Hemicrania Continua). - Lithium: Mood stabilizer (Preventive option for Cluster Headache, esp. chronic). - Melatonin: May help Cluster Headache prevention. - Corticosteroids: (e.g., Prednisone) Used for short-term transitional therapy to break cluster cycles or induce remission while long-term preventives take effect (CH, sometimes other TACs).
Preventive Therapy - Neuromodulation/Interventional	- Greater Occipital Nerve (GON) Block: Injection of local anesthetic +/- steroid (Can provide temporary relief/abort cluster cycles in CH, sometimes helpful in other TACs). - Occipital Nerve Stimulation (ONS): Implanted device (Considered for medically refractory chronic Cluster Headache). - Sphenopalatine Ganglion (SPG) Stimulation: Implanted device (Investigational/approved in some regions for refractory chronic Cluster Headache). - Vagal Nerve Stimulation (VNS): Non-invasive device applied to neck (Approved in some regions for episodic/chronic Cluster Headache). - Deep Brain Stimulation (DBS): Targeting posterior hypothalamus (Experimental, for highly refractory chronic Cluster Headache).
Preventive Therapy - Biologics	- CGRP Monoclonal Antibodies: (e.g., Galcanezumab approved for episodic Cluster Headache prevention). Erenumab, Fremanezumab studied with variable results in CH. Role in other TACs less clear.

Note: Choice of therapy must be based on accurate ICHD-3 diagnosis, patient factors, and careful consideration of efficacy and side effects. Indomethacin trial is mandatory if PH or HC is suspected.

Headache and Migraine Treatment

Treatment strategies for headache are highly dependent on the specific diagnosis (primary vs. secondary headache type) and individual patient factors (frequency, severity, duration of attacks, presence of aura, impact on quality of life, comorbidities, patient preferences, previous treatment responses). Accurate diagnosis according to ICHD-3 criteria is paramount before initiating therapy.

General approaches include:

• Acute (Abortive/Rescue) Treatment: Aims to stop or significantly reduce the severity and associated symptoms of a headache attack once it has started. Should be taken as early as possible in the attack for best effect. Examples include:
  • Simple Analgesics: Acetaminophen (paracetamol), NSAIDs (ibuprofen, naproxen sodium, diclofenac, aspirin).
  • Combination Analgesics: Often contain caffeine, aspirin/acetaminophen +/- butalbital (use limited due to MOH/dependence risk).
  • Migraine-Specific Acute Treatments:
    • Triptans: Serotonin 5-HT_1B/1D receptor agonists (sumatriptan, rizatriptan, zolmitriptan, eletriptan, almotriptan, frovatriptan, naratriptan) available in various formulations (oral, nasal spray, injection). First-line for moderate/severe migraine attacks. Contraindicated in uncontrolled hypertension, ischemic heart/vascular disease.
    • Gepants: Small molecule CGRP receptor antagonists (ubrogepant, rimegepant for acute treatment). Offer alternative for those who cannot take or do not respond to triptans.
    • Ditans: Selective 5-HT_1F receptor agonist (lasmiditan). Alternative for acute migraine, lacks vasoconstrictive effects but can cause CNS side effects (dizziness, sedation - driving restrictions).
    • Ergots: Dihydroergotamine (DHE - nasal spray, injection), ergotamine tartrate (oral, suppository - use limited by side effects/vasoconstriction).
  • Cluster Headache Specific: High-flow Oxygen (100% at 12-15 L/min via non-rebreather mask), subcutaneous or nasal sumatriptan.
  • Adjunctive: Antiemetics (metoclopramide, prochlorperazine, ondansetron) for nausea/vomiting, often given with acute treatment.
• Preventive (Prophylactic) Treatment: Aims to reduce the frequency, severity, and/or duration of headache attacks, improve responsiveness to acute treatments, and reduce disability. Considered when attacks are frequent (e.g., ≥4 headache days/month or ≥8 for chronic migraine), severe, prolonged, debilitating, cause significant disability despite optimal acute treatment, or if acute treatments are poorly tolerated/contraindicated/overused. Options vary by headache type and include:
  • Migraine Prevention:
    • Oral Medications: Beta-blockers (propranolol, metoprolol, timolol), Antidepressants (amitriptyline, venlafaxine), Anticonvulsants (topiramate, valproate).
    • Injectable Biologics: CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab).
    • Injectable Neurotoxin: OnabotulinumtoxinA (Botox®) for Chronic Migraine only.
    • Oral Gepants: Rimegepant, atogepant approved for migraine prevention.
    • Other: Candesartan, Lisinopril, certain supplements (magnesium, riboflavin, CoQ10) may have benefit.
  • Tension-Type Headache Prevention: Amitriptyline is first-line for chronic TTH. Other options less established (mirtazapine, venlafaxine, topiramate, gabapentin, physical therapy, CBT).
  • Cluster Headache Prevention: Verapamil (first-line, requires high dose, ECG monitoring), Lithium (esp. chronic CH), Galcanezumab, Topiramate, Melatonin. Transitional therapy (corticosteroids, GON block).
  • Other TACs Prevention: Indomethacin (absolute response defines PH, HC), Lamotrigine (SUNCT/SUNA).
• Treatment of Secondary Headaches: Primarily focuses on addressing the underlying cause (e.g., treating infection with antibiotics, managing ICP with medication/shunting, stopping offending medication in MOH, treating sinus disease, managing hypertension, surgical removal of tumor, treating GCA with steroids). Symptomatic headache relief may also be needed concurrently.
• Non-Pharmacological Approaches: Important adjuncts or sometimes primary therapy. Include:
  • Lifestyle Modifications: Maintaining regular sleep schedules, regular meals, adequate hydration, regular aerobic exercise, managing stress.
  • Identification and Avoidance of Triggers: If specific, consistent triggers are identified (e.g., certain foods, alcohol, sensory stimuli, stress let-down) - though evidence is variable and over-restriction should be avoided.
  • Behavioral Therapies: Cognitive Behavioral Therapy (CBT), Biofeedback, Relaxation training (progressive muscle relaxation, guided imagery). Strong evidence base, particularly for migraine and TTH.
  • Physical Therapies: Exercise, manual therapy (massage, mobilization), posture correction, especially for TTH and cervicogenic headache.
  • Acupuncture: Evidence supports efficacy comparable to some pharmacological preventives for migraine and potentially TTH [15].
  • Neuromodulation Devices: Various devices targeting trigeminal nerve, vagus nerve, or occipital nerves are available or under investigation (e.g., supraorbital transcutaneous stimulation, non-invasive VNS, single-pulse transcranial magnetic stimulation).

Management requires individualized treatment plans, realistic expectations, patient education, and regular follow-up to assess efficacy, tolerability, and adjust therapy as needed. Addressing comorbid conditions (e.g., depression, anxiety, sleep disorders) is also crucial for optimal headache management.

Specific treatment modalities that might be employed include:

• Pharmacological Therapy (Acute and preventive medications tailored to specific headache diagnosis and patient profile).
• Peripheral Nerve Blocks / Trigger Point Injections (e.g., Greater Occipital Nerve (GON) blocks for occipital neuralgia, cluster headache, migraine; trigger point injections for myofascial pain contributing to tension-type or cervicogenic headache).
• Lumbar Puncture (Primarily diagnostic; therapeutic only in specific circumstances like IIH symptom relief or post-LP headache treatment with epidural blood patch).
• Physiotherapy Modalities (Heat, cold, TENS, ultrasound - often used adjunctively for symptom relief).
• Physical Therapy / Therapeutic Exercise (Essential for cervicogenic headache, helpful for TTH, adjunct for migraine focusing on posture, strength, relaxation).
• Reflexotherapy (Acupuncture) (Evidence supports efficacy for prevention of migraine and tension-type headache).
• Surgical Intervention (Rarely indicated for primary headaches themselves; necessary for certain secondary causes like tumors, aneurysms, Chiari malformation, or refractory trigeminal neuralgia - e.g., microvascular decompression, radiosurgery). Migraine "trigger site" surgery remains controversial.

Attention! While most headaches are benign primary types, sudden severe headaches or headaches with neurological symptoms ("red flags") require immediate medical evaluation to rule out serious underlying causes. Self-treating frequent or severe headaches without a proper diagnosis can be ineffective and potentially delay treatment for a serious condition or lead to medication-overuse headache. Consult a healthcare professional for accurate diagnosis and management.

References

1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202
2. Ray BS, Wolff HG. Experimental studies on headache; pain-sensitive structures of the head and their significance in headache. Arch Surg. 1940;41(4):813–57. doi: 10.1001/archsurg.1940.01210040002001
3. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of Migraine: A Disorder of Sensory Processing. Physiol Rev. 2017 Apr;97(2):553-622. doi: 10.1152/physrev.00034.2015
4. Dodick DW. Diagnosing headache: a crucial step toward effective treatment. Postgrad Med. 2000;107(4):33-4, 37-40. doi: 10.3810/pgm.2000.04.1023
5. Dodick DW. Clinical Practice. Chronic daily headache. N Engl J Med. 2006 Jan 12;354(2):158-65. doi: 10.1056/NEJMcp052855
6. American College of Radiology. ACR Appropriateness Criteria® Headache. Revised 2019. Available from: https://acsearch.acr.org/docs/69483/Narrative/
7. American Headache Society Position Statement on Surgical Decompression of Migraine Headache Trigger Sites. Headache. 2020;60(8):1740-1742. doi: 10.1111/head.13968
8. American Headache Society Consensus Statement: Integrating New Migraine Treatments Into Clinical Practice. Headache. 2019 Jan;59(1):1-18. doi: 10.1111/head.13456
9. Diener HC, et al. Medication-overuse headache: a worldwide problem. Lancet Neurol. 2004 Nov;3(11):725-7. doi: 10.1016/S1474-4422(04)00932-3
10. Goadsby PJ, Lipton RB. A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain. 1997 Jan;120 ( Pt 1):193-209. doi: 10.1093/brain/120.1.193
11. Antonaci F, Sjaastad O. Chronic paroxysmal hemicrania (CPH): a review of the clinical manifestations. Headache. 1989 Nov;29(10):648-56. doi: 10.1111/j.1526-4610.1989.hed2910648.x
12. Cittadini E, Goadsby PJ. Hemicrania continua: a clinical study of 39 patients with diagnostic implications. Brain. 2010 Jul;133(7):1973-86. doi: 10.1093/brain/awq138
13. Goadsby PJ. Pathophysiology of cluster headache: a trigeminal autonomic cephalalgia. Lancet Neurol. 2002 Aug;1(4):251-7. doi: 10.1016/s1474-4422(02)00068-6
14. Wei DY, Yuan Ong JJ, Goadsby PJ. Cluster Headache: Epidemiology, Pathophysiology, Clinical Features, and Diagnosis. Ann Indian Acad Neurol. 2018;21(Suppl 1):S3-S8. doi: 10.4103/aian.AIAN_349_17
15. Linde K, et al. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev. 2016 Jun 28;(6):CD001218. doi: 10.1002/14651858.CD001218.pub3
16. Chaibi A, Russell MB. Manual therapies for primary chronic headaches: a systematic review of randomized controlled trials. J Headache Pain. 2014;15:67. doi: 10.1186/1129-2377-15-67