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Secondary Headache Red Flags

What Do You Need to Know?

SNOOP mnemonic: Systemic symptoms, Neurologic signs, Onset sudden, Onset >50, Pattern change/Positional/Papilledema/Pregnancy
Thunderclap headache: SAH until proven otherwise; non-contrast CT within 6 h = 98–100% sensitive; LP for xanthochromia if CT negative
IIH: papilledema + elevated OP (>25 cm H₂O) + normal MRI; acetazolamide first-line (IIHTT: 500 mg BID); MRV mandatory to exclude CVT
SIH: orthostatic headache, diffuse pachymeningeal enhancement, brain sagging — “SEEPS” mnemonic; epidural blood patch if conservative measures fail
Post-traumatic: new headache within 7 days of trauma; persistent if >3 months; treat based on phenotype it resembles
Pregnancy/postpartum: always exclude CVT, preeclampsia, RCVS, PRES, pituitary apoplexy
New headache >50 yr: GCA, mass lesion, or subdural hematoma until proven otherwise — ESR + CRP + temporal artery biopsy

Red Flag Assessment — SNOOP

SNOOP Mnemonic

S — Systemic symptoms: fever, weight loss, known cancer, HIV, immunosuppression
N — Neurologic symptoms/signs: focal deficits, altered consciousness, seizures, papilledema, meningismus
O — Onset sudden: thunderclap headache (<1 min to peak intensity)
O — Onset after age 50: new headache → GCA, mass lesion, subdural hematoma until proven otherwise
P — Pattern change / Progressive / Positional / Precipitated by Valsalva / Papilledema / Pregnancy or Postpartum

Red Flags → Diagnosis → Workup

Red Flag	Suspected Diagnosis	Workup
Thunderclap onset (<1 min)	SAH, CVT, RCVS, dissection	CT head → LP → CTA/MRA
Fever + meningismus	Meningitis/encephalitis	LP (emergent), blood cultures
Papilledema	IIH, mass lesion, CVT	MRI + MRV → LP with OP
New onset >50 yr	GCA, mass, SDH	ESR, CRP, MRI brain, temporal artery biopsy
Worse with Valsalva	Chiari, posterior fossa mass, IIH	MRI brain + craniocervical junction
Positional (orthostatic)	SIH	MRI brain with gadolinium → spine MRI/CT myelogram
Progressive over weeks	Mass lesion, chronic SDH, CVT	MRI brain with contrast + MRV
Pregnancy/postpartum	CVT, preeclampsia, RCVS, PRES	MRI/MRV, BP monitoring, urine protein
Immunocompromised	CNS infection, lymphoma, PML	MRI brain, LP (cytology, cultures, PCR)
Systemic cancer + new headache	Brain metastases, leptomeningeal disease	MRI brain with contrast, LP cytology

💎 Board Pearl

Any “worst headache of my life” or headache reaching peak intensity in <1 minute = thunderclap → must rule out SAH regardless of other features

Thunderclap Headache Workup

Differential Diagnosis

SAH — most critical to exclude; ruptured aneurysm in 85%
CVT — headache in >90%; progressive or thunderclap
RCVS — recurrent thunderclap; “string of beads” on angiography
Arterial dissection — ipsilateral neck pain; Horner syndrome (carotid)
Pituitary apoplexy — visual field cuts, ophthalmoplegia
Colloid cyst (3rd ventricle) — positional thunderclap; acute hydrocephalus → sudden death
Meningitis — fever, meningismus, altered mental status
Hypertensive emergency — SBP >180 / DBP >120 with end-organ damage

Stepwise Workup

Step 1: Non-Contrast CT Head

First-line imaging; look for hyperdense blood in basal cisterns, Sylvian fissures, interhemispheric fissure
Sensitivity depends on time from onset (see table below)

Step 2: Lumbar Puncture (if CT Negative)

Perform ≥6–12 h after onset to allow xanthochromia to develop
Xanthochromia: yellow discoloration from bilirubin; spectrophotometry more sensitive than visual inspection
RBC count: tube 1 vs. tube 4 — traumatic tap clears; SAH does not

Step 3: Vascular Imaging

CTA: aneurysm, dissection, CVT; MRA/MRV: alternative if contrast contraindicated
Conventional angiography if CTA/MRA negative but high suspicion — gold standard for RCVS, vasculitis

CT Sensitivity for SAH by Time from Ictus

Time from Onset	CT Sensitivity	Clinical Implication
<6 hours	98–100%	Near-perfect; controversy about LP need if negative
6–12 hours	~93%	LP recommended if CT negative
12–24 hours	~85%	LP mandatory if CT negative
2–5 days	~75%	Blood resorbing; MRI FLAIR may help
1 week	~50%	CT unreliable; LP + vascular imaging essential

💎 Board Pearl

CT at <6 h has near-100% sensitivity for SAH (Perry 2011: 100% in 953 patients) — debate about LP necessity if negative
Classic board question: thunderclap + negative CT → next step = LP for xanthochromia (not “reassure and discharge”)

Clinical Pearl

RCVS: recurrent thunderclap over 1–4 weeks with normal initial CTA — repeat imaging may reveal vasoconstriction; resolves within 3 months

Idiopathic Intracranial Hypertension (IIH)

Modified Dandy Criteria

Papilledema on fundoscopic exam
Normal neurologic exam (except CN6 palsy — false localizing sign from elevated ICP)
Elevated opening pressure: >25 cm H₂O in adults; >28 cm H₂O in children
Normal CSF composition (cell count, protein, glucose)
Normal MRI brain (or only showing signs of elevated ICP) + MRV to exclude CVT

Demographics & Presentation

Demographics: obese women of childbearing age (BMI >30); F:M = 8:1
Headache: daily, diffuse, worse with Valsalva/coughing/bending
Transient visual obscurations: seconds-long graying/blacking out — due to papilledema
Pulsatile tinnitus: whooshing synchronous with heartbeat
Diplopia: CN6 palsy — false localizing sign of elevated ICP
Visual field loss: enlarged blind spot early; progressive constriction if untreated

MRI Signs of Elevated ICP

Empty sella, optic nerve sheath distension (>2 mm), flattened posterior globe
Transverse sinus stenosis (bilateral in ~90%), tortuous optic nerves

Treatment

Medical

Weight loss: 5–10% = significant improvement
Acetazolamide: first-line (IIHTT: 500 mg BID, up to 4 g/day); carbonic anhydrase inhibitor → ↓ CSF production
Topiramate: weight loss + carbonic anhydrase inhibition; Furosemide: second-line diuretic

Surgical

ONSF: progressive visual loss despite medical therapy
CSF diversion: VP/LP shunt for refractory headache ± visual loss
Venous sinus stenting: transverse sinus stenosis with gradient ≥8 mmHg

Medications Causing IIH

Medication	Notes
Tetracyclines (minocycline, doxycycline)	Most commonly tested; stop immediately
Vitamin A / retinoids (isotretinoin)	Hypervitaminosis A
Growth hormone	Especially in children
Lithium	Rare but well-documented
Corticosteroid withdrawal	Rebound intracranial hypertension

💎 Board Pearl

MRV is mandatory in every IIH workup — CVT can perfectly mimic IIH and requires anticoagulation, not acetazolamide
Fulminant IIH with rapid vision loss → urgent optic nerve sheath fenestration (do not wait for weight loss or medication effect)

Spontaneous Intracranial Hypotension (SIH)

Clinical Features

Hallmark: orthostatic headache — worse upright, improves within 15 min supine
May become constant over time (positional component less obvious chronically)
Associated: neck stiffness, nausea, photophobia, muffled hearing, CN6 palsy
Cause: CSF leak from dural tear — most commonly thoracic spine
CSF: low OP (<6 cm H₂O) but normal in up to 30%; may have elevated protein/lymphocytic pleocytosis

Diagnostic Findings

MRI Brain with Gadolinium — “SEEPS”

S — Subdural fluid collections (hygromas/hematomas)
E — Enhancement of pachymeninges (diffuse, smooth; NO leptomeningeal)
E — Engorgement of venous sinuses
P — Pituitary enlargement
S — Sagging brain (tonsillar descent, pons flattened on clivus)
Leak localization: spine MRI → CT myelography (gold standard) → radionuclide cisternography

Treatment

Step	Intervention	Details
1. Conservative	Bed rest, hydration, caffeine, abdominal binder	Effective in ~30% over 1–2 weeks
2. Epidural blood patch	15–30 mL autologous blood injected epidurally	First-line procedural treatment; 30–90% success; may need repeat
3. Targeted therapy	CT-guided fibrin glue, surgical repair	For identified leak sites refractory to blood patch

💎 Board Pearl

Diffuse pachymeningeal enhancement (not leptomeningeal) = SIH until proven otherwise — DDx includes neurosarcoidosis and meningeal carcinomatosis, but SIH is far more common
SIH can mimic Chiari I malformation due to cerebellar tonsillar descent — always check for pachymeningeal enhancement before planning posterior fossa decompression

Cervicogenic Headache

Diagnostic Criteria (ICHD-3)

Unilateral without side-shift; starts in neck, radiates to frontotemporal region
Aggravated by neck movement, sustained posture, or pressure over upper cervical/occipital region
Reduced cervical ROM; must have evidence of causative cervical disorder (imaging or clinical)
Most commonly involves C2–3 zygapophysial (facet) joint

Key Differentiators from Migraine

Feature	Cervicogenic	Migraine
Side	Strictly unilateral, non-alternating	Unilateral or bilateral; can alternate
Origin	Starts in neck/occiput	Starts in head
Triggered by	Neck movement/posture	Stress, sleep, hormones, sensory
Neck ROM	Reduced	Normal
Diagnostic block	Abolishes headache	Does not abolish headache

Treatment

Physical therapy (first-line): cervical mobilization, postural correction
Nerve blocks: greater occipital nerve or C2–3 facet injection (diagnostic + therapeutic)
Radiofrequency ablation: C2–3 medial branch for refractory cases; medications have limited role

Clinical Pearl

A diagnostic anesthetic block of the C2–3 facet joint or greater occipital nerve that abolishes the headache is the strongest evidence supporting a cervicogenic diagnosis

Post-Traumatic Headache

Classification (ICHD-3)

Acute: develops within 7 days of head trauma or regaining consciousness
Persistent: continues >3 months after onset
Most common after mild TBI/concussion; paradoxically more prevalent after mild than severe TBI

Phenotypes & Treatment

Phenotype	Frequency	Treatment Approach
Migraine-like	Most common (~50–60%)	Triptans, CGRP mAbs, preventives (topiramate, amitriptyline)
Tension-type-like	~30%	NSAIDs, amitriptyline, physical therapy
Cervicogenic	~15–20%	Physical therapy, nerve blocks
Occipital neuralgia	~5–10%	Occipital nerve blocks, gabapentin

Key Points

Screen for medication overuse (≥10–15 analgesic days/month) — common complicating factor
Comorbidities (PTSD, depression, insomnia) contribute to persistence; no FDA-approved treatment — manage by phenotype

💎 Board Pearl

Post-traumatic headache is treated based on the primary headache phenotype it most closely resembles — if it looks like migraine, treat as migraine; if it looks like tension-type, treat accordingly

Headache in Special Populations

Pregnancy & Postpartum

CVT: hypercoagulable state; headache + seizure + focal deficits; MRV diagnostic; anticoagulate with LMWH
Preeclampsia/eclampsia: HTN + proteinuria ± seizures; onset ≥20 wk; magnesium sulfate for seizures
RCVS: postpartum thunderclap; vasoactive triggers; supportive care + CCBs
Pituitary apoplexy / PRES: thunderclap + visual loss; posterior white matter edema (PRES) — treat BP

Elderly (>50 Years)

GCA: temporal headache, jaw claudication, visual loss; ESR ≥50; biopsy = gold standard; start prednisone 60–80 mg immediately
Mass / chronic SDH: progressive headache, focal deficits; history of falls/anticoagulation
Hypnic headache: “alarm clock headache” — only during sleep; age >50; caffeine before bed = treatment

Immunocompromised

CNS infections: toxoplasmosis (ring-enhancing), cryptococcosis (elevated OP), PML (JC virus)
Primary CNS lymphoma: periventricular enhancing; EBV-associated in HIV/AIDS

Summary Table

Population	Top Diagnoses	Key Workup
Pregnant/postpartum	CVT, preeclampsia, RCVS, PRES	MRI/MRV, BP, urinalysis, labs
Age >50	GCA, mass, chronic SDH	ESR/CRP, MRI brain, temporal artery biopsy
Immunocompromised	CNS infection, lymphoma	MRI brain with contrast, LP (cytology, PCR, cultures)
Cancer history	Brain metastases, leptomeningeal disease	MRI brain with contrast, LP cytology

💎 Board Pearl

GCA: start high-dose prednisone immediately when clinical suspicion is high — do not delay treatment waiting for temporal artery biopsy (remains positive for ≥2 weeks on steroids)
Any new headache in a postpartum patient → MRV to rule out CVT before attributing to primary headache

References

Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (ICHD-3). Cephalalgia. 2018;38(1):1–211.
Perry JJ, et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage. BMJ. 2011;343:d4277.
Wall M, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). JAMA. 2014;311(16):1641–1651.
Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006;295(19):2286–2296.
Do TP, et al. Red and orange flags for secondary headaches in clinical practice: SNNOOP10 list. Neurology. 2019;92(3):134–144.
Dodick DW. Thunderclap headache. J Neurol Neurosurg Psychiatry. 2002;72(1):6–11.