HA DX

HA pathophysiology: First: irritation of nociceptors connected to CN V[…] supplying the dura mater[…] → release NTs: vasoactive peptide, substance P, and CGRP[…]; They act on mast cells[…] to release histamine + prostaglandins[…] → vasodilate BVs + increase capillary permeability; They also act directly on BVs to release NO[…] → similar response; Inflammatory mediators activate nearby nociceptors → action potentials down CN V → trigeminal ganglion → trigeminal nucleus → thalamus → primary somatosensory cortex.

Pathophysiology of aura: Effects above increase release of K+ and glutamate[…] from neurons faster than glial cells can clear → triggers Cortical Spreading Depression[…] (sustained propagating depolarization, self-regenerating positive feedback loop) → burns itself out (explains visual aura → temporary scotoma); High serotonin[…] often seen in aura → acts on 5-HT receptors → vasoconstricts BVs; Low serotonin[…] → associated with vasodilation and migraine without aura.

Phases: Prodromal[…] symptoms: start before aura/headache; Postdrome[…] symptoms: after pain (e.g., "brain fog"/fatigue).

Aura symptoms (unlike stroke/TIA, occur in succession[…] rather than simultaneously): Visual: flashing lights, zigzag lines, scotomas, field cuts, tunnel vision, metamorphopsia, transient visual loss; Somatosensory: numbness/paresthesias; Speech: expressive aphasia; Auditory: hallucinations; Weakness, vertigo, Alice in Wonderland[…] syndrome.

Pain characteristics: Migraine: starts in neck[…], spreads anteriorly; throbbing/pounding; not side-locked; TAC: almost always centered around one eye[…]; side-locked[…]; Tension: bilateral, bandlike pressure; Cluster: stabbing/knifelike; Nummular HA[…]: patient can point out well-circumscribed round/oval area; Hemicrania continua: side-locked.

Special patterns: Thunderclap HA[…]: DDX = SAH, RCVS, meningitis, SIH; Nocturnal awakening: tumors, nocturnal HTN, cluster, paroxysmal hemicrania, hypnic HA[…]; Morning HA: most common time for migraine.

Associated symptoms: Migraine: photo/phono/osmophobia, n/v/d, aura — prefer to lie down in dark/quiet[…], worsens with activity; Cutaneous allodynia[…] from failure of central sensitization of trigeminal nucleus caudalis; TAC: ptosis/miosis, lacrimation, conjunctival injection, rhinorrhea/congestion → restlessness/agitation[…] (thrashing in bed). Duration: SUNCT/SUNA: seconds-minutes; Paroxysmal hemicrania: 2-30 min; Tension HA: 30 min-7 days; Cluster: 15 min-3 hours; Migraine: 4 hr-3 days.

Red flags: Systemic (fever/weight loss) → malignancy/infection; New/sudden → SAH, RCVS, CVT, dissection; >50 yo → GCA[…]; Positional → SIH/IIH or tumor; Valsalva-precipitated → CSF leak or Chiari/posterior fossa; Papilledema → IIH (look for TVOs, pulsatile tinnitus, obesity, tetracycline/vit A/Li use); Pregnancy/postpartum → CVT/CVST, pituitary apoplexy, PRES, RCVS; Painful eye + autonomic → ophthalmic emergency or TAC; Posttraumatic → ICH or CSF leak.

Timing: most effective early in aura/prodrome[…] or before cutaneous allodynia[…] develops.

N/V: ondansetron, metoclopramide, prochlorperazine[…] (try nonoral given nausea).

Headache pain — nonspecific: Tylenol (SE: hepatotoxicity at high doses); NSAIDs (SE: GI bleed, renal dysfunction, MI risk); Combination analgesics like Excedrin (ASA/Tylenol/caffeine)[…]; AVOID butalbital[…] combinations (bulbital/caffeine/ASA or tylenol) — poor efficacy + worsens HA burden.

Migraine-specific: Triptans[…]: 5-HT1B/D agonists. Most effective: SC sumatriptan, ODT rizatriptan, ODT zolmitriptan, PO eletriptan.

SE: overuse HA, facial flushing[…]; CI in vascular disease, hemiplegic or brainstem migraine.

DHE[…] nasal spray (ergot derivative): vasoconstriction; long-term use → retroperitoneal/pleural fibrosis.

-Gepants[…]: ubrogepant (Ubrelvy), rimegepant (Nurtec)[…].

Avoid with strong CYP3A4[…] inhibitors.

Lasmiditan[…]: 5-HT1F agonist. SE rare: dizziness, fatigue, paresthesias. Neuromodulation devices: REN, vagus nerve stim, TMS, trigeminal nerve stim.

Algorithm: Mild-moderate: 1st line OTCs → or if vascular risks: -Gepants or lasmiditan[…] (no vasoconstriction); Moderate-severe: 1st line triptans[…] → switch triptan/increase dose → -gepants/lasmiditan → neuromodulation.

Pregnant patients: N/V: ondansetron, metoclopramide; benadryl, flexeril; Pain: 1st line Tylenol or NSAIDs[…] → 2nd line triptans; AVOID DHE, -gepants, lasmiditan[…].

ER patients: antiemetic (metoclopramide or prochlorperazine) + SC sumatriptan + IV magnesium[…] + IV fluids.: Refractory: dexamethasone[…] (doesn't reduce pain acutely but reduces recurrence) vs VPA vs IV DHE 1mg Q8H; AVOID opioids[…] (medication overuse risk).

Definition: preexisting HA disorder with HA ≥15 days/month[…] due to overuse of meds ≥10-15 days/month[…] for >3 months.

Thresholds: Tylenol/NSAIDs: ≥15 days/month; Combination analgesics, triptans, ergots, opioids[…], or any combination: ≥10 days/month. Presentation: daily or near-daily HA with no characteristic pattern; variable from migraine to tension.

Pathophys: chronic medication exposure → neuronal hyperexcitability[…] in cortex + trigeminal system → increased peripheral and central sensitization[…].: Tylenol changes 5-HT receptor expression in cortex; Opioids and triptans increase frequency of cortical spreading depression; fMRI: reduced activity in pain matrix, especially orbitofrontal cortex + cerebellum[…] (not all reversible).

Bridge therapy during withdrawal: PO naproxen[…] or short prednisone[…] taper; IV VPA or prochlorperazine or DHE (requires hospital or infusion center).

Agents with efficacy: Topamax[…]; CGRPs; Botox[…]; Address underlying psychiatric disease burden via therapies.

TACs: Cluster HA, Paroxysmal Hemicrania, Hemicrania Continua, SUNCT/SUNA[…]. Shared symptoms: unilateral pain + ipsilateral autonomic symptoms.

Indomethacin response: Paroxysmal Hemicrania and Hemicrania Continua[…] respond; others do NOT. Cluster HA: Can be episodic or chronic (shorter/absent remission periods).

Comorbidities: sleep apnea, MDD/GAD, smoking, suicidal ideation[…] (rates drop during remission).

Symptoms: severe attacks (1-2/day) in periorbital[…] location, each 1-2 hours + autonomic + restlessness[…] (pacing, rocking, hitting head — unlike migraine patients who prefer to lie still). Cycle ~6-12 weeks, ~1x/year. Autonomic: conjunctival injection, ptosis, miosis, lacrimation, nasal congestion/rhinorrhea — migraine can have these but bilaterally. Side-locked in most patients (one side whole life).

Triggers: alcohol, nitroglycerin, heat[…] (exercise, hot showers). Circadian rhythmicity: attacks ~same time daily (~2 AM).

Indomethacin trial[…]: cluster does NOT respond (helps differentiate from PH). Like migraine: can have photo/phonophobia + n/v + premonitory yawning.

Diagnostics: MRI with pituitary and cavernous sinus[…] views (rule out tumors, CVST mimics). Pathophys: hypothalamus + trigeminovascular + autonomic system.

Key neuropeptides: CGRP and VIP[…]. O2 blocks signals from autonomic to trigeminovascular system.

Treatment: Acute: high-flow O2 via NRB mask[…] + SC sumatriptan. Nasal zolmitriptan or lidocaine. Episodic cluster: noninvasive vagus nerve stim. Bridge: 1st line steroids 100 mg × 5 days + taper + occipital nerve block.

Preventives (chronic or >2-3 week cycles): verapamil[…] 120 mg TID up to 360 mg TID. SE: heart block — get EKG.

Galcanezumab (Emgality) 300 mg monthly for episodic only[…]. Refractory chronic cluster: implantable occipital nerve stimulator or hypothalamic DBS or sphenopalatine stimulator. Pregnancy: O2 + IN lidocaine + SC sumatriptan.

SUNCT/SUNA: Very short, chronic, sharp/stabbing/electric pain in groups or sawtooth[…] pattern; Often multiple per day[…] (28+) — unlike cluster (several/day, circadian); Triggers: contact to face (wind, brushing, chewing, touching); SUNCT[…]: with Conjunctival injection + Tearing; SUNA[…]: with Cranial Autonomic features (CI, tearing, OR neither); Both can be caused by vascular compression of trigeminal nerve[…].

DDX: Unlike trigeminal neuralgia: no refractory period[…] (can be re-triggered); Unlike primary stabbing HA: no autonomic features. Diagnostics: MRI brain with detailed pituitary, cavernous sinus, brainstem views (rule out compression/tumors).

Treatment (attacks too short for acute Rx → focus on bridge + prevention): Bridge: IV lidocaine drip[…] (requires 1-week admission with continuous tele; CI: arrhythmias) or steroids; Prevention: 1st line lamotrigine[…] or other Na+ channel blockers (similar to trigeminal neuralgia).

Paroxysmal hemicrania: PET: activation of contralateral posterior hypothalamic + ventral midbrain[…]; ≥5 attacks/day of severe unilateral orbital/supraorbital/temporal pain up to 30 min[…] ± 1 ipsilateral autonomic symptom; Patients may sit still during attacks (unlike cluster); Cluster vs PH: cluster is less frequent, longer duration, often circadian, alcohol trigger, not[…] responsive to indomethacin; Diagnostics: MRI brain + pituitary to rule out pituitary mass ± hormone labs; Treatment: indomethacin + PPI/H2B[…] → noninvasive vagus nerve stimulation.

Hemicrania continua: PET: contralateral posterior hypothalamic + dorsal rostral pons + ventrolateral midbrain (contrast: cluster activates ipsilateral[…] posterior hypothalamic); Unilateral persistent/continuous HA ± migrainous features >3 months + at least one ipsilateral autonomic symptom + responsive to indomethacin[…]; Episodes are hours (not paroxysmal) and continuous/worsening (not discrete attacks); Treatment: indomethacin + PPI/H2B → noninvasive vagus nerve stimulation.

Etiology: post-TBI.: Acute[…] posttraumatic HA: <3 months; Persistent[…] posttraumatic HA: ≥3 months. Risk factors: pre-existing migraine or psychiatric disease before TBI. Most common phenotypes: migraine-like, tension-like, rarely TAC-like or cervicogenic-like.

Pathophys: Neuroinflammation from mast cell/microglia activation → propensity for cortical spreading depolarization → trigeminal activation; Neuropeptides (CGRP/NO)[…] → central sensitization; Altered pain processing; Structural brain changes → functional connectivity changes.

Diagnostic criteria: HA must occur <7 days[…] of TBI, regaining of consciousness, or discontinuation of medications that impaired headache reporting.

Associated symptoms (postconcussive syndrome): Cutaneous allodynia[…] from peripheral or central sensitization; Mood or sleep changes; Cognitive issues described as "brain fog"; Sometimes autonomic dysfunction. No specific characteristics/diagnostics. If preexisting HA worsens post-TBI, patient diagnosed with BOTH disorders. Imaging: to rule out secondary HA causes (ICH, CSF leak, skull fracture, dissection). Treatment: Per phenotype it resembles. Abortives: triptans if migrainous; NSAIDs if tolerated.

Avoid opioids[…] (increase persistence risk).

Preventives: watch for cognitive dysfunction with Topamax[…]. TCAs for pain or orthostatic hypotension. β-blockers for orthostatic hypotension.

Occipital nerve blocks[…] if occipital tenderness to palpation.

Symptoms: Acute onset[…] of continuous, unilateral headache ≥3 months without alternative cause; Patients can often recall the day of onset[…] (key distinguishing feature); ± Ipsilateral autonomic symptoms. Phenotype: Migraine-like more common, with bilateral autonomic symptoms + rare unilateral pain (unlike migraine); Tension-type HA phenotype also possible. Pathophysiology: Often a trigger:.

Viral infection[…]: most common (e.g., COVID-19, ACE2 receptor) — direct neuronal entry via olfactory bulbs[…] → trigeminovascular activation → cytokine release → inflammation. Hypothesized mechanism of long-COVID. Vaccination. Stress.

Diagnostics: MRI brain with and without contrast to rule out SIH[…] → other SIH workup as indicated; Indomethacin[…] trial to rule out hemicrania continua.

Treatment: Abortives: triptans; Preventives:; TCAs (nortriptyline)[…] — SE: dry mouth, constipation, urinary retention, weight gain; ASMs: Topamax (cognitive, kidney stones, weight loss, acute angle-closure glaucoma[…]); VPA (weight gain, tremor, hair loss, hepatotoxicity, pancreatitis, thrombocytopenia); β-blockers (propranolol); SNRIs (venlafaxine ER) — SE: HTN, sexual dysfunction; CGRPs; Botox injections or nerve blocks.

Thunderclap HA → SAH or RCVS[…]; Progressively worsening HA → secondary HA[…]; HA worse lying down → IIH[…]; HA worse standing → SIH[…]; Valsalva-triggered → vascular pathology or space-occupying lesion (Chiari I); Side-locked unilateral eye pain + cranial autonomic symptoms → pituitary or cavernous sinus[…] issues; Morning HA with vomiting → high ICP[…]; Morning HA alone → OSA[…]; Abdominal migraine → high risk of developing migraine HA; HA + photo/phonophobia + n/v → migraine HA; Tension HA → pancranial/bilateral pressing/tightening pain; TAC → severe side-locked unilateral periorbital pain + ipsilateral autonomic symptoms; Brief seconds-long stabbing pain or series of stabs, responsive to indomethacin → primary stabbing HA[…]; Unrelenting ≥3 months daily HA → NDPH[…]; Papilledema → IIH or ICP increase.

1st line: NSAIDs[…] like ibuprofen 10 mg/kg vs naproxen. Other options: similar to adults (triptans, antiemetics, CGRP, neuromodulation devices).

All kids should be screened for anxiety/depression[…].

Symptoms: brief, lancinating, shock-like pain, often unilateral, localizable to a nerve distribution. Pathophys: Involves both peripheral + central mechanisms; Injury to peripheral nerve → demyelination[…] → amplified pain signals activated by light touch; Central neurodegeneration → increases risk of Alzheimer disease[…] + depression + anxiety.

Trigeminal Neuralgia (Tic Douloureux): Recurrent paroxysms of unilateral facial pain lasting fraction of second to minutes in ≥1 trigeminal division; Very intense, sharp/stabbing, superficial, "electric shock[…]" sensation; Triggered by innocuous stimuli (light touch, cold wind, chew/speak/brush/shave); DDX: if prominent autonomic features → think SUNCT/SUNA[…].

Treatment: 1st line meds: Na+ channel blockers — carbamazepine[…] (SE: dizziness/ataxia, hypoNa, aplastic anemia, SJS) and oxcarbazepine (SE: hyponatremia); 2nd line: gabapentin, lamotrigine, lacosamide, baclofen, botox; Exacerbations: IVF + IV fosphenytoin vs IV lidocaine vs IV vimpat; Refractory: nerve blocks + botox; Still refractory: microvascular decompression[…] of trigeminal nerve vs ablative procedures.

Glossopharyngeal neuralgia: Very rare; recurrent paroxysms of unilateral pain seconds-minutes; severe, shooting, "electric shock" in CN IX distribution; Triggered by swallow, cough, talk, yawn; Unique features (due to CN X involvement): cough, hypophonia, bradycardia and syncope[…]; Treatment: similar to TN.

Nervus intermedius neuralgia: Extremely rare; pain deep in auditory canal[…] seconds-minutes; sensory root of facial nerve; May have lacrimation, salivation, taste issues; Etiology: vascular compression or HSV[…] infection; Diagnostics: MRI for compression near brainstem entry zone.

Occipital neuralgia: Anatomy:; C2 dorsal ramus → Greater Occipital Nerve[…] (posterior scalp to vertex); C2 ventral ramus → Lesser Occipital Nerve (lateral posterior scalp); C3 dorsal ramus → Lower Occipital Region; Symptoms: recurrent paroxysmal attacks (secs-mins), severe, shooting/stabbing in distribution of occipital nerve branches + dysesthesia + allodynia; May have point of emergence tenderness of Greater Occipital Nerve[…]; Pathophys: irritation or compression of occipital nerve branches; Treatment: same meds as other neuralgias or memantine[…] (case reports) → occipital nerve blocks q3-4 months[…] + PT/OT → decompressive surgery.

Both are TACs: paroxysmal hemicrania + hemicrania continua. Indomethacin: Inhibits COX[…] (mostly COX1 selectivity vs other NSAIDs like ibuprofen/naproxen); Blocks prostaglandin[…] synthesis from arachidonic acid; SE: dyspepsia (treat with H2B/PPI), n/v; Raises lithium levels[…] — toxicity risk; Can lower CSF pressure → false interpretation in patients with high ICP.

Pathophys: both share activation of trigeminal-autonomic reflex[…]: Trigeminal afferents via V1 → superior salivatory nucleus in pons → efferent fibers via geniculate ganglion → join deep petrosal nerve → sphenopalatine ganglion → PS outflow → autonomic symptoms.

Paroxysmal hemicrania: PET: activation of contralateral posterior hypothalamic + ventral midbrain[…]; >5 attacks/day, severe unilateral orbital/supraorbital/temporal pain up to 30 min[…] ± 1 ipsilateral autonomic symptom (ptosis/miosis, conjunctival injection, lacrimation, eyelid edema, nasal congestion/rhinorrhea); Sense of restlessness internally but physically may sit still during attacks (unlike cluster); Cluster vs PH: cluster is less frequent, longer duration, circadian, alcohol trigger, un[…]responsive to indomethacin.

Hemicrania continua: PET: contralateral posterior hypothalamic + dorsal rostral pons + ventrolateral midbrain (contrast cluster: ipsilateral); Unilateral persistent/continuous HA ± migrainous features ≥3 months[…] + ≥1 ipsilateral autonomic symptom + responsive to indomethacin; Episodes are hours (vs paroxysmal hemicrania attacks ≤30 min); Continuous and may worsen over time (unlike discrete attacks).

Treatment for both: indomethacin + PPI/H2B[…] → noninvasive vagus nerve stimulation.

For new-onset Bell palsy, prednisone[…] (or other corticosteroids) offers the best chance of full recovery and has the highest level of evidence.

Should be started within 72[…] hours of symptom onset for maximum effect.

The safest and most appropriate medication for mild, tension-type headaches during the first trimester is acetaminophen[…].

Butalbital and hydrocodone[…] should be avoided due to risks of fetal complications or dependency.

Ibuprofen[…] should be avoided in the 1st and 3rd trimesters.

The maxillary division of the trigeminal nerve (V2[…]) travels through the lateral wall of the cavernous[…] sinus but NOT through the orbital apex[…].

Cluster headache with coronary artery disease should be aborted with high-flow oxygen[…] via non-rebreather mask — effective, rapid, and no vasoconstrictive cardiac risk.

Triptans and ergotamines[…] are contraindicated in heart disease.

Abrupt onset of daily persistent headache after COVID-19 with normal exam and MRI in a teen with no prior headaches is diagnostic for New Daily Persistent Headache[…]. Gradual onset, migrainous features, abnormal imaging, or recurrent attacks point away from this diagnosis.

SUNCT[…] = short unilateral neuralgiform with Conjunctival injection + Tearing.

SUNA[…] = short unilateral neuralgiform with cranial Autonomic features (CI, tearing, OR neither).

Both treated with lamotrigine[…] (Na+ channel blocker) as first-line preventive.

First-line preventive for cluster headache is verapamil[…] 120 mg TID up to 360 mg TID.

SE: heart block[…] — get EKG before initiating and during dose escalation.

Paroxysmal hemicrania and hemicrania continua[…] are exquisitely responsive to indomethacin — used as both diagnostic test and treatment. Other TACs (cluster, SUNCT/SUNA) do NOT respond.

Co-administer PPI or H2B[…] due to GI side effects.

First-line treatment for trigeminal neuralgia is carbamazepine or oxcarbazepine[…] (Na+ channel blockers).

Carbamazepine SE: dizziness/ataxia, hyponatremia[…], aplastic anemia, SJS.

Refractory cases: microvascular decompression[…].

Medication-overuse headache definition: HA ≥15[…] days/month due to overuse of meds for ≥3 months.

Thresholds: simple analgesics (Tylenol/NSAIDs) ≥15 days/month; combination analgesics, triptans, ergots, or opioids[…] ≥10 days/month.