SNNOOP10 Mnemonic

• S — Systemic symptoms: fever, weight loss, night sweats
• S — Systemic disease: known neoplasm, HIV, immunosuppression
• N — Neurologic signs/symptoms: focal deficits, altered consciousness, seizures, meningismus
• N — Neoplasm history: brain metastases, leptomeningeal disease (subsumed under systemic disease)
• O — Onset sudden: thunderclap headache (<1 min to peak intensity)
• O — Older age: new or progressive headache >50 yr → GCA, mass lesion, subdural hematoma
• P — Pattern change / Progressive: escalating frequency or severity, new headache type
• P — Positional: orthostatic (SIH) or recumbent-worse (elevated ICP)
• P — Precipitated by Valsalva: cough, exertion, sex → posterior fossa lesion, Chiari, IIH
• P — Papilledema: IIH, CVT, mass lesion
• P — Painful eye with autonomic features: cluster, dissection, cavernous sinus pathology, acute angle-closure glaucoma
• P — Posttraumatic onset: headache within 7 days of trauma; subdural, post-traumatic headache
• P — Pathology of the immune system (HIV): opportunistic CNS infection, primary CNS lymphoma
• P — Painkiller overuse / new drug at onset: medication overuse headache; vasoactive or other inciting agent

Red Flags → Diagnosis → Workup

Differential Diagnosis

• SAH — most critical to exclude; ruptured aneurysm in 85%
• CVT — headache in ~90%, usually subacute/progressive; thunderclap in ~10% (cortical vein rupture)
• RCVS — recurrent thunderclap; “string of beads” on angiography
• Carotid dissection — ipsilateral neck/face pain + partial Horner (ptosis + miosis without anhidrosis — sudomotor fibers travel with the external carotid) + anterior circulation TIA/stroke
• Vertebral dissection — occipital/posterior neck pain + posterior circulation stroke (e.g., Wallenberg)
• Pituitary apoplexy — thunderclap headache, bitemporal hemianopsia, ophthalmoplegia (cavernous sinus); emergent IV hydrocortisone 100 mg before imaging-directed intervention; transsphenoidal decompression if visual compromise
• 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 ≥12 hours after onset for reliable xanthochromia detection (bilirubin requires ~12 h to form from RBC breakdown)
• Xanthochromia: yellow discoloration from bilirubin; spectrophotometry more sensitive than visual inspection
• RBC count tube 1 vs. tube 4: RBC count decreases substantially from tube 1 to tube 4 in traumatic tap; remains stable in SAH; xanthochromia remains the gold standard
• Some guidelines (ACEP 2019) accept CT-only or CT+CTA in <6 h presentation as an alternative to LP

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

SAH Grading & Treatment

• Nimodipine 60 mg PO q4h × 21 days — vasospasm/DCI prevention (improves outcomes, not vessel caliber)
• Aneurysm securing: ISAT trial — endovascular coiling associated with better 1-year independence vs surgical clipping in suitable anterior circulation aneurysms
• Manage rebleeding risk (BP control), hydrocephalus (EVD), seizure prophylaxis (selective), hyponatremia (cerebral salt wasting)

Friedman 2013 Diagnostic Criteria (supersedes Modified Dandy)

• Papilledema on fundoscopic exam
• Normal neurologic exam (except CN6 palsy — false localizing sign from elevated ICP)
• Elevated opening pressure: strictly >25 cm H₂O in adults; >28 cm H₂O in children. OP must be measured in the lateral decubitus position with legs extended, non-sedated
• Normal CSF composition (cell count, protein, glucose)
• Normal MRI brain (or only showing signs of elevated ICP); MRI brain with venography, or CT/CTV when MRI unavailable, is required to exclude CVT and structural causes before LP-based IIH diagnosis

IIH Without Papilledema (Friedman 2013)

• If no papilledema is present, diagnosis requires CN6 palsy OR ≥3 of 4 MRI features:
  • Empty sella
  • Posterior globe flattening
  • Distended optic nerve sheath (with or without tortuosity)
  • Transverse sinus stenosis
• All other criteria (elevated OP, normal CSF, exclusion of secondary causes) must still be met

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) — start 500 mg BID, titrate to maximum tolerated dose (up to 4 g/day in IIHTT); 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 or optic nerve sheath fenestration: for threatened/declining vision or fulminant IIH; do NOT use shunting as routine treatment for headache alone — manage headache phenotype separately
• Venous sinus stenting: transverse sinus stenosis with gradient ≥8 mmHg

Medications Causing IIH

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: OP may be low (<6 cm H₂O) but is normal in up to ~50–60% of SIH; diagnosis should not be excluded by a normal OP. 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 (dynamic or digital subtraction for CSF-venous fistula); radionuclide cisternography has been largely supplanted

Treatment

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

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

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

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

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. Preeclampsia can present up to 6 weeks postpartum (late postpartum preeclampsia) — maintain suspicion in any postpartum headache with HTN
• 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, visual loss, polymyalgia rheumatica overlap; jaw claudication is the strongest individual predictor (LR+ ~4–8); ESR ≥50 (but normal in up to 20%); CRP more sensitive than ESR; combined ESR + CRP both normal → high NPV
• GCA biopsy: temporal artery biopsy ≥1–2 cm specimen (skip lesions); contralateral biopsy if first negative and suspicion remains high
• GCA treatment: start prednisone 60–80 mg/day immediately when suspected; IV methylprednisolone 1 g/day × 3 days if visual involvement (amaurosis fugax, AION, vision loss)
• 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

Clinical Features

• Unilateral headache + red eye + mid-dilated, non-reactive pupil
• Halos around lights, blurred vision, nausea/vomiting (often misattributed to migraine or gastroenteritis)
• Cornea hazy/steamy; globe firm on palpation

Diagnosis & Treatment

• Tonometry: IOP >40 mmHg (normal 10–21)
• Emergent ophthalmology consult — sight-threatening
• Medical: topical timolol, topical pilocarpine, IV acetazolamide ± mannitol
• Definitive: laser peripheral iridotomy

Anticoagulation

• Anticoagulate regardless of hemorrhagic infarction (ISCVT 2004) — venous infarcts are not a contraindication
• Acute: LMWH (preferred over UFH) → transition to warfarin (INR 2–3) or DOAC
• Duration:
  • Provoked (e.g., pregnancy, OCP, transient trigger): 3–6 months
  • Unprovoked: 6–12 months
  • Persistent severe thrombophilia or recurrent CVT: lifelong
• Endovascular thrombectomy: select patients with clinical deterioration despite anticoagulation
• Manage ICP, seizures, and underlying provoker (stop OCP, treat infection, evaluate for thrombophilia)

Red Flags Suggesting Secondary TN

• Bilateral symptoms
• Age <40 years
• Sensory deficit in trigeminal distribution
• V1 involvement (ophthalmic division)
• Poor or absent response to carbamazepine
• Associated cranial nerve deficits

Workup

• MRI with thin-section trigeminal sequences (high-resolution 3D T2/FIESTA/CISS + post-contrast) to exclude:
  • Multiple sclerosis (demyelinating plaque at root entry zone)
  • Vestibular schwannoma / cerebellopontine angle mass
  • Arteriovenous malformation
  • Other compressive or infiltrative lesion

Diagnostic Frame

• Autosomal dominant small-vessel arteriopathy from NOTCH3 mutations on chromosome 19p13 — cysteine-altering mutations cause granular osmiophilic material (GOM) deposits in arteriolar smooth muscle.
• Classic clinical tetrad:
  1. Migraine with aura (often the earliest manifestation, age 20s–30s; ~40% of patients) — frequently atypical, prolonged, hemiplegic, or with confusion.
  2. Recurrent subcortical lacunar strokes / TIAs (4th–5th decade) — often without conventional vascular risk factors.
  3. Mood disturbance (depression, apathy; ~20–30%).
  4. Progressive subcortical vascular dementia (60s) with gait disturbance and pseudobulbar features.

Imaging Signature

• Confluent T2/FLAIR hyperintensities in the anterior temporal poles and external capsules — near-pathognomonic, often present before symptoms.
• Subcortical lacunar infarcts (basal ganglia, thalamus, pons, deep white matter); microbleeds on SWI.
• Spares U-fibers and cortex (unlike CARASIL, which has more lumbar/pontine arch and alopecia).

Diagnosis & Management

• Genetic testing for NOTCH3 is the gold standard; skin biopsy showing GOM by electron microscopy is supportive when genetics ambiguous.
• No disease-modifying therapy; aggressive vascular risk factor control, antiplatelet for stroke prevention (avoid anticoagulation unless other indication — microbleed burden).
• Avoid triptans and ergotamines in CADASIL migraine due to small-vessel disease and stroke risk (case-by-case decision; CGRP-targeted therapy is a safer preventive option).