Clinical Headache

Headache Mimics & Facial Pain

Headache Mimics & Facial Pain

What Do You Need to Know?

  • GCA: Age >50, new headache, jaw claudication (most specific symptom), ESR/CRP elevated, temporal artery biopsy gold standard (skip lesions → get ≥1 cm); start steroids BEFORE biopsy
  • RCVS: Recurrent thunderclap headaches, “string of beads” on angiography, normal CSF, resolves <3 months; distinguish from PACNS (insidious onset, abnormal CSF, progressive course)
  • Trigeminal neuralgia: V2/V3 > V1, brief electric shock-like pain triggered by light touch, carbamazepine first-line, MRI for neurovascular compression (SCA most common vessel)
  • Glossopharyngeal neuralgia: Ear/throat lancinating pain triggered by swallowing; can cause syncope via vagal reflex; rule out Eagle syndrome
  • Tolosa-Hunt syndrome: Painful ophthalmoplegia from granulomatous cavernous sinus inflammation; dramatic steroid response
  • Key distinction: Thunderclap + normal CSF + reversible = RCVS; insidious + abnormal CSF + progressive = PACNS
Giant Cell Arteritis (GCA)

Epidemiology

  • Age >50 (mean onset ~70 years); almost never occurs before age 50
  • Female:male ratio 2–3:1
  • Highest incidence in Northern European descent (Scandinavian populations)
  • Polymyalgia rheumatica (PMR) overlap: 40–60% of GCA patients have PMR; ~15% of PMR patients develop GCA

Clinical Features

  • New-onset headache: Temporal region, often unilateral, persistent; most common presenting symptom (~75%)
  • Jaw claudication: Pain with chewing that resolves with rest — most specific clinical feature (LR+ ~34); caused by ischemia of masseter/temporalis muscles
  • Scalp tenderness: Pain when brushing hair or resting head on pillow
  • Vision loss: Most feared complication; anterior ischemic optic neuropathy (AION) — pale disc edema; permanent if untreated
  • Diplopia: CN3, CN4, or CN6 palsy from vasa nervorum ischemia
  • Constitutional symptoms: Fever, weight loss, malaise, fatigue
  • Tongue claudication: Less common but highly specific

Laboratory & Diagnostic Studies

Test Findings Key Points
ESR Typically >50 mm/hr (often >100) Sensitivity ~85%; can be normal in 5–10% (“occult GCA”)
CRP Elevated More sensitive than ESR alone; combined ESR + CRP sensitivity >95%
CBC Thrombocytosis, normocytic anemia Thrombocytosis correlates with disease activity
Temporal artery biopsy Gold standard; granulomatous inflammation with giant cells, intimal hyperplasia, fragmented internal elastic lamina Get ≥1 cm (ideally 2 cm); skip lesions reduce sensitivity (~85%); bilateral biopsy if unilateral negative + high suspicion
Temporal artery ultrasound Halo sign — hypoechoic wall thickening Sensitivity ~77%, specificity ~96%; operator-dependent; increasingly used as first-line imaging
18F-FDG PET/CT Vascular wall uptake Best for large-vessel GCA (aorta, subclavian, axillary); complements temporal biopsy

ACR/EULAR 2022 Classification Criteria

  • Requires age ≥50 + score ≥6 from: temporal artery abnormality, ESR ≥50 or CRP ≥10, morning stiffness, sudden visual loss, jaw/tongue claudication, temporal artery biopsy/halo sign
  • Designed for classification (research), not diagnosis — but clinically useful framework

Treatment

  • High-dose prednisone 40–60 mg/day: Start IMMEDIATELY upon clinical suspicion — do NOT wait for biopsy
  • IV methylprednisolone 1 g/day × 3 days: If vision threatened (acute visual loss, impending second eye involvement)
  • Tocilizumab (IL-6 receptor inhibitor): GiACTA trial demonstrated superior relapse-free remission vs. prednisone alone at 52 weeks; used as steroid-sparing agent
  • Slow prednisone taper over 12–24 months; monitor ESR/CRP for relapse
  • Low-dose aspirin: consider for prevention of ischemic complications
  • Biopsy remains positive for up to 2 weeks after steroid initiation
💎 Board Pearl
  • Jaw claudication is the most specific clinical feature of GCA (LR+ ~34)
  • Start steroids BEFORE biopsy — temporal artery biopsy remains positive for up to 2 weeks after steroid initiation; delaying treatment risks permanent vision loss
RCVS vs. PACNS

Reversible Cerebral Vasoconstriction Syndrome (RCVS)

  • Recurrent thunderclap headaches (peak intensity <1 min) over 1–3 weeks
  • Young to middle-aged women; common triggers: vasoactive drugs (triptans, SSRIs, sympathomimetics, cannabis), postpartum, exertion, Valsalva, sexual activity
  • Angiography: “string of beads” pattern — multifocal segmental vasoconstriction of medium/large cerebral arteries
  • CSF: normal (critical distinguishing feature from PACNS)
  • Complications: convexity SAH (most common hemorrhage type), ICH, ischemic stroke (usually later in course)
  • Course: self-limited; resolves within 12 weeks; angiographic normalization by 3 months

Primary Angiitis of the CNS (PACNS)

  • Insidious progressive headache over weeks to months
  • Focal neurological deficits, cognitive decline, personality changes
  • CSF: abnormal in ~90% — elevated protein, lymphocytic pleocytosis
  • MRI: white matter lesions, multifocal infarcts in multiple vascular territories
  • Angiography: may show beading but can be normal (small vessel vasculitis undetectable)
  • Brain biopsy is gold standard — granulomatous or lymphocytic vasculitis of small/medium leptomeningeal and cortical vessels
  • Treatment: cyclophosphamide + high-dose corticosteroids; progressive without treatment

RCVS vs. PACNS: Key Differentiating Features

Feature RCVS PACNS
Headache onset Thunderclap (<1 min peak) Insidious (weeks–months)
Age/sex Young–middle-aged women Any age; slight male predominance
Triggers Vasoactive drugs, postpartum, exertion None
CSF Normal Abnormal (↑ protein, pleocytosis)
Angiography “String of beads” — reversible Beading or normal (small vessel)
Course Self-limited; resolves <12 weeks Progressive without treatment
Complications Convexity SAH, ICH, ischemic stroke Multifocal infarcts, cognitive decline
Diagnosis Clinical + reversible vasoconstriction Brain biopsy (gold standard)
Treatment CCB (verapamil/nimodipine); remove triggers Cyclophosphamide + corticosteroids
💎 Board Pearl
  • RCVS = thunderclap + normal CSF + reversible; PACNS = insidious + abnormal CSF + progressive
  • Triptans and ergots are CONTRAINDICATED in RCVS — they are vasoconstrictors and may worsen vasospasm, precipitating stroke
Trigeminal Neuralgia (TN)

Clinical Features

  • Classic TN (type 1): Brief, paroxysmal, electric shock-like pain in trigeminal distribution
  • Duration: Seconds to <2 minutes per attack; occurs in clusters with refractory periods between attacks
  • Distribution: V2/V3 >> V1 (V1 alone is the least common distribution)
  • Triggered by non-noxious stimuli (allodynia): Light touch to face, wind, washing face, eating, talking, brushing teeth, shaving
  • Between attacks (type 1): Pain-free intervals; no neurological deficits
  • TN type 2 (atypical): Continuous background aching/burning pain with superimposed paroxysms
  • Trigger zone: typically nasolabial fold or perioral region

Etiology & Neurovascular Compression

  • SCA (superior cerebellar artery): Most common vessel causing neurovascular compression of CN5 at the root entry zone
  • Compression → focal demyelination of trigeminal root → ephaptic transmission (cross-talk between pain and touch fibers)
  • MRI protocol: High-resolution sequences (CISS/FIESTA) to visualize neurovascular contact
  • MRI also to exclude secondary causes: MS plaques, CPA tumors, skull base lesions

Secondary Causes

  • Multiple sclerosis: Bilateral TN in a young patient → strongly consider MS; demyelinating plaque at pontine root entry zone
  • CPA tumors: Vestibular schwannoma (acoustic neuroma), meningioma, epidermoid cyst
  • Skull base lesions: Chordoma, metastasis, Meckel cave lesion
  • Red flags for secondary TN: age <40, bilateral symptoms, sensory loss, abnormal trigeminal reflex

Treatment

Treatment Details Key Points
Carbamazepine First-line; NNT 1.7–1.8 Best evidence of any medication for TN; check HLA-B*1502 in Asian descent (SJS/TEN risk)
Oxcarbazepine First-line alternative Better tolerability than CBZ; fewer drug interactions; risk of hyponatremia
Baclofen Add-on therapy Useful in combination with CBZ/OXC; can be used as monotherapy if CBZ not tolerated
Lamotrigine Second-line Slow titration required; useful for TN type 2 with continuous pain component
MVD (microvascular decompression) Surgical first-line Highest long-term success: ~80% pain-free at 10 years; Teflon pad placed between vessel and nerve
Percutaneous rhizotomy Radiofrequency, balloon, glycerol For patients who are poor surgical candidates; higher recurrence than MVD; causes some facial numbness
Gamma Knife radiosurgery Focused radiation to trigeminal root Least invasive; delayed onset of relief (weeks–months); lower success rate than MVD
💎 Board Pearl
  • Bilateral TN in a young patient = think MS — demyelinating plaque at the pontine root entry zone of CN5
  • SCA is the most common vessel causing trigeminal neurovascular compression
Glossopharyngeal Neuralgia (GPN)

Clinical Features

  • Lancinating, electric shock-like pain in CN9 distribution: ear, tonsillar fossa, base of tongue, angle of jaw, deep pharynx
  • Triggers: Swallowing, talking, coughing, yawning, chewing
  • Brief paroxysms (seconds to <2 min); similar temporal pattern to TN
  • Much rarer than TN (incidence ~0.7/100,000 vs. TN ~12/100,000)

Vagoglossopharyngeal Neuralgia

  • GPN + syncope/bradycardia/asystole: CN9 afferents → nucleus tractus solitarius (NTS) → dorsal motor nucleus of vagus → cardioinhibitory reflex
  • Can cause life-threatening cardiac arrest during pain paroxysms
  • May require cardiac pacing in addition to GPN treatment

Secondary Causes to Exclude

  • Eagle syndrome: Elongated styloid process (>3 cm) or calcified stylohyoid ligament compressing CN9; diagnosed by CT
  • CPA tumors, oropharyngeal/skull base malignancy, vascular compression (PICA most common)

Treatment

  • Carbamazepine/oxcarbazepine: First-line (same as TN)
  • MVD of CN9: Surgical option for refractory cases; separates compressing vessel from CN9/CN10 root entry zone
  • Intracranial sectioning of CN9 + upper rootlets of CN10 if MVD fails
💎 Board Pearl
  • Glossopharyngeal neuralgia + syncope = CN9 afferents → NTS → vagal cardioinhibitory reflex (“vagoglossopharyngeal neuralgia”)
Occipital Neuralgia

Clinical Features

  • Sharp, shooting, stabbing pain in distribution of greater occipital nerve (GON) or lesser occipital nerve (LON)
  • GON = C2 dorsal ramus (medial branch of C2); innervates posterior scalp to vertex
  • Paroxysmal pain with or without continuous aching between attacks
  • Tenderness over occipital notch (GON exit point, ~1/3 of the way lateral from external occipital protuberance)
  • May radiate anteriorly to the forehead via trigeminocervical convergence (C2 → trigeminal nucleus caudalis)

Etiology

  • Post-traumatic (whiplash, direct trauma), C1–C2 arthropathy, muscular entrapment (semispinalis, trapezius)
  • Cervicogenic causes: degenerative disc disease, Arnold-Chiari malformation
  • Often idiopathic

Diagnosis & Treatment

  • GON block with local anesthetic ± steroid: Diagnostic AND therapeutic — positive response confirms diagnosis
  • Preventive: gabapentin, pregabalin, tricyclic antidepressants
  • Botulinum toxin injection: emerging evidence for refractory cases
  • Rarely: surgical decompression, occipital nerve stimulation (ONS), or pulsed radiofrequency
Clinical Pearl
  • Do not confuse occipital neuralgia with cervicogenic headache or migraine with occipital predominance — GON block response helps differentiate, but can also partially improve cervicogenic headache and migraine via trigeminocervical convergence
Other Facial Pain Syndromes

Tolosa-Hunt Syndrome

  • Painful ophthalmoplegia from granulomatous inflammation of the cavernous sinus or superior orbital fissure
  • Unilateral periorbital/retro-orbital pain + ipsilateral CN3, CN4, CN6, or V1 involvement
  • MRI: enhancing lesion in cavernous sinus (contrast-enhanced with fat suppression)
  • Dramatic response to corticosteroids (pain relief within 72 hours) — part of diagnostic criteria
  • Diagnosis of exclusion: must rule out tumor, lymphoma, sarcoidosis, IgG4-related disease, carotid-cavernous fistula, infection

Persistent Idiopathic Facial Pain

  • Formerly “atypical facial pain”
  • Daily, deep, poorly localized facial pain; does not follow nerve distribution
  • No neurological deficits on exam; no structural or organic cause found
  • Diagnosis of exclusion after thorough workup (MRI, dental evaluation)
  • Treatment: TCAs (amitriptyline), SNRIs (duloxetine), CBT; avoid opioids

Burning Mouth Syndrome

  • Burning sensation of tongue, palate, lips; often bilateral
  • Most common in postmenopausal women (F:M 7:1)
  • Normal oral exam; may worsen through the day, improve with eating
  • Etiology likely small fiber neuropathy of intraoral mucosa
  • Treatment: clonazepam (topical or systemic), alpha-lipoic acid, CBT

Key Facial Pain Syndromes Comparison

Syndrome Location Quality Trigger Treatment
Trigeminal neuralgia V2/V3 (unilateral) Electric shock, seconds Light touch, wind, eating Carbamazepine; MVD
Glossopharyngeal neuralgia Ear, throat, tongue base Lancinating, seconds Swallowing, talking Carbamazepine; MVD CN9
Occipital neuralgia Posterior scalp (C2) Sharp, shooting Neck movement, pressure GON block; gabapentin
Tolosa-Hunt Periorbital/retro-orbital Deep, boring, constant None Corticosteroids
Persistent idiopathic facial pain Variable, poorly localized Deep, aching, constant None TCAs, SNRIs, CBT
Burning mouth syndrome Tongue, palate, lips Burning, continuous None; worsens through day Clonazepam; alpha-lipoic acid
💎 Board Pearl
  • Tolosa-Hunt = painful ophthalmoplegia + cavernous sinus inflammation + dramatic steroid response — always a diagnosis of exclusion; MRI with contrast mandatory to rule out tumor, lymphoma, IgG4 disease

References

  • Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990;33(8):1122–1128.
  • Ponte C, Grayson PC, Engelbrecht M, et al. 2022 ACR/EULAR classification criteria for giant cell arteritis. Ann Rheum Dis 2022;81(12):1647–1653.
  • Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis (GiACTA). N Engl J Med 2017;377(4):317–328.
  • Ducros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol 2012;11(10):906–917.
  • Salvarani C, Brown RD Jr, Hunder GG. Adult primary central nervous system vasculitis. Lancet 2012;380(9843):767–777.
  • Cruccu G, Finnerup NB, Jensen TS, et al. Trigeminal neuralgia: new classification and diagnostic grading for practice and research. Neurology 2016;87(2):220–228.