1. Thought broadcast - Schneider's first-rank symptoms include thought insertion, thought withdrawal, thought broadcast, made feelings/impulses/actions, somatic passivity, delusional perception, and third-person auditory hallucinations.
2. Depression - Depression is by far the most common psychiatric disorder in primary care settings.
3. Delusion of reference - The belief that external stimuli (TV, radio, newspapers) are sending special messages to oneself is a classic delusion of reference.
4. Dopamine - Antipsychotics block D2 receptors in the nigrostriatal pathway, causing Parkinsonian side effects (tremor, rigidity, bradykinesia).
5. SSRI - SSRIs (e.g., sertraline, paroxetine) are first-line pharmacotherapy for panic disorder per all major guidelines.
6. Thought blocking - Thought blocking is a negative/formal thought disorder symptom, NOT a feature of mania. The others (grandiosity, increased goal-directed activity, flight of ideas) are all classic manic symptoms.
7. Alcohol - Alcohol is the most widely abused substance globally by prevalence and burden of disease.
8. Neuroleptic Malignant Syndrome (NMS) - The tetrad of hyperthermia, rigidity, autonomic instability, and elevated CPK following antipsychotic use = NMS.
9. Sublimation - Sublimation (channeling unacceptable impulses into socially acceptable behavior) is a mature/adaptive defense mechanism. Projection, denial, and splitting are immature/primitive.
10. Disturbance of attention and awareness - Delirium is defined by acute fluctuating disturbance in attention and awareness (DSM-5), not by clear consciousness or stable deficits.
11. Phenelzine - Phenelzine is an MAOI. MAOIs + tyramine-rich foods = hypertensive crisis ("cheese reaction"). SSRIs like fluoxetine, sertraline, and escitalopram do not carry this risk.
12. Intrusive thoughts recognized as one's own - The hallmark of OCD is ego-dystonic obsessions - intrusive, unwanted thoughts the patient recognizes as their own but cannot control.
13. Naloxone - Naloxone is the immediate antidote for opioid overdose (competitive opioid receptor antagonist). Naltrexone is for relapse prevention, not acute reversal.
14. Fine tremors - Fine hand tremors are the most common side effect of lithium. Hypothyroidism (not hyperthyroidism) and nephrogenic diabetes insipidus are other important side effects.
15. ADHD - Persistent inattention and hyperactivity/impulsivity in multiple settings (school AND home) in a child is the classic presentation of ADHD.
16. Avolition - Avolition (lack of motivation/goal-directed behavior) is a negative symptom. Delusions, hallucinations, and thought insertion are positive symptoms.
17. Compulsion - Repetitive, purposeful behavior performed in response to an obsession (checking the door) despite recognizing it as irrational = compulsion.
18. Lorazepam/Diazepam - Benzodiazepines are the drug of choice for delirium tremens, as they enhance GABA activity and prevent seizures/autonomic instability.
19. Borderline Personality Disorder - Recurrent self-harm and suicidal gestures are a hallmark feature of BPD (DSM-5 criterion 5).
20. ECT (Electroconvulsive Therapy) - ECT is the gold standard for severe depression with psychotic features, catatonia, or high suicidal risk due to its rapid onset of action.
21. Attention span and working memory - The Digit Span Test (forward and backward) primarily assesses immediate attention and working memory.
22. Running commentary hallucinations - Voices that discuss or comment on the patient's actions in third person = running commentary, which is also a Schneiderian first-rank symptom.
23. Naltrexone - Naltrexone (opioid antagonist) is FDA-approved for alcohol use disorder relapse prevention (reduces craving/reward). Acamprosate and disulfiram are also approved options.
24. Cognitive impairment - The MMSE is a standardized screening tool for cognitive impairment and dementia (max score 30; <24 suggests impairment).
25. Bipolar I disorder - Bipolar I = at least one full manic episode (with or without depressive episodes). Bipolar II = hypomanic + major depressive episodes, with NO full mania.

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Management of Stroke - Detailed Overview

---

1. Overview and Classification

• Ischemic stroke (~80-85%): Thrombotic or embolic occlusion of a cerebral artery
• Hemorrhagic stroke (~15-20%): Intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH)
• Transient Ischemic Attack (TIA): Transient focal neurological deficit without infarction

---

2. Initial Emergency Assessment (Both Types)

Immediate ABCs

• Airway: Protect airway; if GCS ≤8, intubate (use fentanyl 2-3 mcg/kg IV first to prevent ICP spike from tracheal stimulation)
• Breathing: Pulse oximetry; supplemental O2 if SpO2 < 94%; assisted ventilation if needed
• Circulation: IV access, cardiac monitoring for ≥48 hours; immediate 12-lead ECG and troponin (concomitant MI occurs in 3-20% of strokes)

Neurological Assessment

• NIH Stroke Scale (NIHSS): Quantify deficits; NIHSS >15 indicates large infarct
• Assess consciousness, language, cranial nerves, visual fields, motor/sensory function, cerebellar function

Emergency Labs

Emergency Imaging

• Non-contrast CT head: First-line; rules out hemorrhage (takes <5 minutes)
• CT Angiography (CTA): If thrombectomy is being considered (large vessel occlusion)
• CT Perfusion or MRI/DWI: Distinguishes infarcted core from viable penumbra; guides late window treatment

---

3. Management of Acute Ischemic Stroke

A. Stroke Unit Admission

• Bradley and Daroff's Neurology in Clinical Practice, p. 1405

B. IV Thrombolysis (Alteplase / rt-PA)

• 10% as IV bolus over 1 minute
• Remaining 90% as infusion over 60 minutes

• BP must be <185/110 mmHg before giving alteplase (lower first with labetalol or nicardipine if needed)
• Blood glucose >50 mg/dL
• No intracranial hemorrhage on CT

From Rosen's Emergency Medicine (Table 87.5, 2019 AHA/ASA guidelines), p. 1435

C. Mechanical Thrombectomy (Endovascular Therapy)

• Recommended up to 24 hours from last-known-well in selected patients (DAWN, DEFUSE-3 criteria based on CT perfusion mismatch)
• Can be performed in addition to or instead of IV alteplase
• Stent retrievers and aspiration catheters are used
• For symptomatic high-grade intracranial stenosis, aggressive medical management is superior to stenting (SAMMPRIS trial - 14% stroke/death with stenting vs. 5.8% with medical therapy at 30 days)

D. Blood Pressure Management in Ischemic Stroke

• Nicardipine (first-line): Start 5 mg/h, titrate by 2.5 mg/h every 5-15 min, max 15 mg/h
• Labetalol: 10 mg IV over 1-2 min, repeat/double every 10-20 min, max 300 mg
• Avoid: Sublingual/immediate-release nifedipine (unpredictable drops); sodium nitroprusside (cerebral vasodilation worsens edema)

E. Blood Glucose Management

• Avoid hyperglycemia (worsens ischemic injury in animal models; associated with hematoma expansion in ICH)
• Avoid hypoglycemia (causes neuronal injury independent of ischemia)
• Target: Maintain near-euglycemia, but intensive glucose control (SHINE, GIST-UK trials) did NOT improve outcomes and increased hypoglycemia risk
• Regular glucose checks; insulin infusion if consistently >180 mg/dL

F. Temperature

• Hyperthermia worsens ischemic injury; treat aggressively with antipyretics
• Mild therapeutic hypothermia is neuroprotective in models but not yet standard practice for ischemic stroke

G. Cerebral Edema Management

1. Elevate head of bed 20-30 degrees
2. Mannitol 0.25-1 g/kg IV over 30 minutes; repeat every 6 hours (max 2 g/kg); controversial in ischemic edema
3. Hypertonic saline (alternative)
4. Hyperventilation: Rapid ICP reduction but only transient; avoid prolonged use
5. Decompressive hemicraniectomy + durotomy: For malignant MCA infarction - proven to improve survival and functional outcome in select patients (Fig. 65.32 - right frontal infarct with subfalcine herniation)
6. Steroids are NOT indicated in ischemic stroke - ineffective and worsen hyperglycemia/BP

• Bradley and Daroff's Neurology in Clinical Practice, pp. 1406-1408

H. DVT/VTE Prophylaxis

• DVT in hemiparetic limb is common; risk persists into post-stroke period
• LMWH preferred: Enoxaparin 40 mg SC once daily (superior to UFH in the PREVAIL trial, though small increase in extracranial hemorrhage)
• Unfractionated heparin (UFH): 5,000 units SC twice daily if LMWH unavailable
• If heparin is contraindicated: Intermittent pneumatic compression (IPC) of lower limbs (CLOTS-3 trial validated)
• Prophylactic heparin can be given safely alongside aspirin

I. Aspiration and Nutrition

• Aspiration pneumonia kills 15-25% of stroke patients
• Formal swallowing evaluation before any oral intake (video-fluoroscopic modified barium swallow)
• Aspiration occurs in >33% of brainstem strokes, 25% bilateral hemispheric, 10% unilateral hemispheric strokes
• If dysphagia present: Nasogastric tube (NGT) feeding; NPO until swallow confirmed safe
• Urinary catheter: Avoid unless urinary retention; remove at earliest opportunity to prevent urosepsis

J. Antiplatelet Therapy (Acute Phase)

• Aspirin 160-325 mg within 24-48 hours of stroke onset (after ruling out hemorrhage, and if not receiving alteplase within 24 hours)
• IST and CAST trials established a modest but significant reduction in early recurrence and mortality
• Dual antiplatelet therapy (DAPT - aspirin + clopidogrel): For minor stroke/TIA with high recurrence risk (ABCD2 score based risk):
  • CHANCE trial (China): 75-300 mg clopidogrel + aspirin for 21 days - reduced 90-day recurrence, no increase in intracranial hemorrhage
  • POINT trial: Similar benefit in non-Asian populations; slight increase in systemic bleeding when extended to 90 days
  • DAPT not appropriate if thrombolysis, thrombectomy, or anticoagulation is planned

---

4. Management of Intracerebral Hemorrhage (ICH)

A. Initial Stabilization

• Secure airway: Intubate if GCS ≤8 (pre-treat with fentanyl 2-3 mcg/kg to blunt ICP rise)
• Emergent CT head to establish location, size, hemorrhage volume
• Neurosurgical consultation immediately
• Labs: CBC, coagulation (PT/INR, aPTT), toxicology, glucose, type & screen

B. Blood Pressure Management in ICH

• Rapid lowering does NOT appear to reduce peri-hematomal perfusion or worsen neurological status
• Preferred agent: IV nicardipine or labetalol (same agents as ischemic stroke)

C. Reversal of Coagulopathy

D. Prevention of Hematoma Expansion

• Tranexamic acid (TICH-2 trial): 1 g IV bolus then 1 g over 8 hours within 8 hours of onset - safe, reduced early deaths and hematoma expansion, but did NOT improve 90-day functional outcomes
• rFVIIa (recombinant activated Factor VII): Phase II showed hematoma growth reduction; Phase III FAST trial showed NO clinical benefit at 90 days and increased arterial thromboembolic complications (10% vs 5%) - not currently recommended
• FASTEST trial is ongoing (targeting very early ICH within 2 hours)

E. Surgical Management of ICH

• Bradley and Daroff's Neurology in Clinical Practice, p. 1438 (eFig 66.20: midline cerebellar hemorrhage with brainstem distortion and hydrocephalus)

F. ICP Management in ICH

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5. Secondary Prevention (Long-Term)

Antiplatelet Therapy

• Aspirin monotherapy: Modestly reduces recurrent stroke and mortality
• Clopidogrel monotherapy: Modest benefit; not dramatically superior to aspirin alone
• Aspirin + clopidogrel long-term: NOT recommended - excess major bleeding outweighs benefit (ACTIVE trial)

Anticoagulation

• For non-cardioembolic ischemic stroke: warfarin is NOT superior to aspirin (WARSS, WASID trials)

Statins

• High-dose statin therapy reduces subsequent stroke by ~2% over 5 years (SPARCL trial)
• Target LDL <70 mg/dL for secondary stroke prevention
• Guidelines recommend statin initiation in all ischemic stroke patients

Carotid Intervention

• Symptomatic carotid stenosis ≥70%: Carotid endarterectomy (CEA) within 2 weeks (best outcomes)
• Symptomatic stenosis 50-69%: CEA may benefit, especially in men
• <50% stenosis: Medical management

Blood Pressure (Long-Term)

• Target BP <130/80 mmHg (or stricter in hemorrhagic stroke)
• Begin antihypertensive therapy once neurological deficit has stabilized (typically after several days in acute stroke)

Lifestyle

• Smoking cessation, physical activity, Mediterranean diet, weight management, alcohol reduction

---

6. Rehabilitation

• Rehabilitation should begin as soon as diagnosis is established and life-threatening complications are stabilized
• Multidisciplinary team: Neurology, physiotherapy, occupational therapy, speech therapy, nutrition, social services
• Screen all patients for rehabilitation candidacy early
• Address shoulder subluxation in hemiplegic patients early
• Fall risk assessment at regular intervals
• Pressure sore prevention: Frequent repositioning, skin inspection, special mattresses

---

7. Complication Prevention Summary

---

Key Management Algorithms

SUSPECTED STROKE
      |
   ABCs + IV access + ECG
      |
   NIHSS assessment
      |
   URGENT CT head (non-contrast)
     /          \
HEMORRHAGE      NO HEMORRHAGE (Ischemic)
    |                  |
ICH/SAH protocol    Check time from onset
Reverse coagulopathy     |
Control BP               |
Neurosurgery consult    <4.5 hrs?    Yes → Assess alteplase eligibility
                         |                  BP <185/110? → Give alteplase 0.9 mg/kg
                        LVO?         No → Antiplatelet + supportive care
                         |
                    Thrombectomy (up to 24h with perfusion imaging)
                         |
              ----STROKE UNIT ADMISSION----
              BP management, glucose control,
              DVT prophylaxis, swallow assessment,
              antiplatelet/anticoagulation, statin,
              rehabilitation

---

---

Transient Ischemic Attack (TIA) - Detailed Overview

---

1. Definition

This is important: a patient whose symptoms resolve in 30 minutes but who has a DWI-positive lesion on MRI is classified as having a stroke, not a TIA. Most TIAs last less than 1 hour in practice.

• Harrison's Principles of Internal Medicine, 22e, p. 3491
• Rosen's Emergency Medicine, p. 1423

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2. Epidemiology and Importance

• Stroke risk after TIA is ~10% at 2 days and 15% at 90 days (up to 22% for ABCD2 score of 7)
• Most strokes occur in the first 2 days after TIA - this is the window where intervention matters most
• TIA is therefore a medical emergency requiring same-day urgent evaluation
• In the US, a stroke occurs every 40 seconds; TIA is a critical warning event preceding many of these
• Frameworks for Internal Medicine, p. 574

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3. Pathophysiology / Causes

Mechanisms:

---

4. Clinical Features

Features by Vascular Territory:

Anterior Circulation (Carotid Territory - MCA/ACA)

Posterior Circulation (Vertebrobasilar Territory)

---

5. Differential Diagnosis

• Frameworks for Internal Medicine, p. 574

---

6. Risk Stratification - The ABCD2 Score

ABCD2 Score Table (Harrison's Principles of Internal Medicine, 22e)

Risk Interpretation and 3-Month Stroke Rate:

Caution: More recent studies have found the ABCD2 score alone does not always provide accurate stroke risk estimation. The ABCD2-I (adding MRI findings) and ABCD3-I (adding dual imaging) improve predictive accuracy but are not yet universally validated.

• Harrison's, Table 438-5; Rosen's, Table 87.6

---

7. Investigations

Immediate (Emergency) Workup

---

8. Management of TIA

A. Admission vs. Outpatient Management

• Rosen's Emergency Medicine, p. 1423

B. Antiplatelet Therapy (Cornerstone of Treatment)

Thrombolysis (alteplase) is CONTRAINDICATED in TIA - the deficit has already resolved. However, the patient should be admitted so thrombolysis can be rapidly administered if symptoms recur.

Dual Antiplatelet Therapy (DAPT) - First-Line for TIA/Minor Stroke

• CHANCE trial (China): DAPT for 21 days reduced 90-day recurrent stroke vs. aspirin alone, no increase in intracranial hemorrhage
• POINT trial (US/international): Similar benefit; slightly increased systemic hemorrhage when extended to 90 days
• Pooled analysis: DAPT most beneficial in first 21 days after TIA/minor stroke
• After 21-90 days: Switch to single antiplatelet (aspirin or clopidogrel monotherapy) to reduce bleeding risk

• Rosen's Emergency Medicine, p. 1423-1424; Harrison's, p. 3492

C. Anticoagulation (for Cardioembolic TIA)

• For new-onset AF: Immediate anticoagulation unless CHA2DS2-VASc score = 0 (men) or 1 (women) with self-terminating paroxysms

D. Statin Therapy

• All TIA patients should receive high-intensity statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg)
• Target LDL <70 mg/dL for secondary prevention
• SPARCL trial: High-dose statin reduced 5-year recurrent stroke by ~2%

E. Blood Pressure Management

• After TIA, begin antihypertensive therapy once neurological status is stable
• Target: <130/80 mmHg long-term
• First-line agents: ACE inhibitors or ARBs (especially with diabetes); thiazide diuretics; calcium channel blockers
• Do NOT aggressively lower BP acutely in the first 24-48 hours (same rationale as ischemic stroke - impaired autoregulation)

F. Carotid Revascularization

• CEA should be performed by surgeons with <6% perioperative stroke/death rate
• Carotid artery stenting (CAS): Alternative to CEA in high surgical-risk patients
• For symptomatic intracranial stenosis: Aggressive medical management is superior to stenting (SAMMPRIS trial)
• Tintinalli's Emergency Medicine, p. 2286

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9. Secondary Prevention (Long-Term)

---

10. Stroke Center Classification and Systems of Care

• Acute Stroke-Ready Hospital (ASRH): Smaller hospitals; initial diagnosis and stabilization; telemedicine link to larger center
• Primary Stroke Center (PSC): Full stroke infrastructure (stroke team, stroke unit, CT/MRI, protocols)
• Comprehensive Stroke Center (CSC): All of the above + advanced imaging, surgery, endovascular thrombectomy

• Rosen's Emergency Medicine, p. 1443

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11. TIA vs. Stroke - Quick Comparison

---

Summary Flowchart

SUSPECTED TIA (resolved focal deficits)
           |
    Urgent CT head (rule out hemorrhage)
           |
    MRI with DWI (preferred - detect silent infarction)
           |
    ABCD2 Score + Vascular imaging (CTA/carotid Doppler) + ECG + Echo
           |
    ┌──────┴──────┐
  High risk      Low risk
  (score ≥4)    (score 0-3)
    Admit         Rapid TIA clinic within 24h
           |
    Initiate DAPT (aspirin + clopidogrel) x 21 days
    Statin (atorvastatin 40-80 mg)
    AF? → DOAC
    Carotid stenosis ≥70%? → CEA within 2 weeks
           |
    Long-term single antiplatelet + risk factor control

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Management of Migraine - Detailed Overview

---

1. Definition and Overview

---

2. Classification (ICHD-III)

• Harrison's Principles of Internal Medicine 22e, Table 441-1

---

3. Diagnostic Criteria (ICHD-III)

Migraine WITHOUT Aura (≥5 attacks required):

1. Headache lasting 4-72 hours
2. At least 2 of the following:
   • Unilateral location
   • Pulsating/throbbing quality
   • Moderate or severe intensity (inhibits or prohibits daily activities)
   • Aggravated by routine physical activity (walking, climbing stairs)
3. During headache, at least 1 of:
   • Nausea and/or vomiting
   • Photophobia AND phonophobia

Migraine WITH Aura (≥2 attacks required):

• Same as above PLUS aura symptoms (fully reversible):
  • Visual: Zigzag lines (fortification spectra), scintillating scotoma, flashing lights - most common aura type (occurs in only 20-25% of migraineurs)
  • Sensory: Ipsilateral arm or periorbital paresthesias/numbness with a "marching" characteristic
  • Motor: Weakness spreading from one area to another (hemiplegic migraine)
  • Speech: Mild dysphasia
• Aura typically lasts 20-60 minutes and precedes the headache

Phases of a Migraine Attack:

• Harrison's Principles of Internal Medicine 22e

---

4. Pathophysiology

1. Cortical spreading depression (CSD): A wave of neuronal/glial depolarization that spreads across the cortex at 3-5 mm/min, believed to be the neural substrate of the aura
2. Trigeminovascular activation: CSD activates trigeminal nerve fibers surrounding meningeal blood vessels → release of vasoactive neuropeptides:
   • CGRP (Calcitonin Gene-Related Peptide) - causes vasodilation and sensitizes pain fibers
   • PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide) - similar role
   • These neuropeptides cause neurogenic inflammation and central sensitization
3. Serotonin (5-HT) role:
   • Plasma/platelet 5-HT levels fluctuate with migraine phases
   • 5-HT-releasing agents (reserpine, fenfluramine) can precipitate migraine
   • Triptans (5-HT1B/1D agonists) abort attacks
   • 5-HT₁B/1D receptor activation: (a) cranial vessel constriction + (b) inhibition of sensory neuropeptide release from perivascular trigeminal afferents + (c) attenuation of TNC (trigeminal nucleus caudalis) excitability
4. Dopamine: Premonitory symptoms (yawning, nausea, hypotension) are dopaminergic; dopamine receptor antagonists (metoclopramide, prochlorperazine) are effective in treatment
5. Ion channel mutations (FHM genes): Mutations in calcium, sodium, and potassium channels alter membrane excitability and predispose to migraine aura

• Harrison's 22e; Goodman & Gilman's Pharmacology

---

5. Triggers

• Hormonal: Menstruation, oral contraceptives, hormone replacement
• Sleep: Too much or too little sleep
• Stress/letdown from stress
• Dietary: Alcohol (red wine), caffeine or caffeine withdrawal, nitrates (processed meats), chocolate, aged cheese, MSG, fasting/missed meals
• Environmental: Barometric pressure changes, strong scents, bright lights, loud noise
• Physical exertion

---

6. Management Overview

┌─────────────────────────────────────────┐
│         MIGRAINE MANAGEMENT             │
├──────────────┬──────────────────────────┤
│  1. Non-     │  Identify & avoid        │
│ Pharmacologic│  triggers; lifestyle     │
│              │  modification            │
├──────────────┼──────────────────────────┤
│  2. Acute    │  Abort the attack when   │
│  (Abortive)  │  it occurs               │
├──────────────┼──────────────────────────┤
│  3.          │  Reduce frequency/       │
│ Prophylactic │  severity (daily meds)   │
└──────────────┴──────────────────────────┘

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7. Non-Pharmacological Management

• Trigger identification and avoidance: Headache diary is invaluable
• Stress management and relaxation techniques (biofeedback, CBT)
• Regular sleep schedule: Avoid excessive or insufficient sleep
• Regular meals: Avoid fasting; maintain consistent meal times
• Regular aerobic exercise: Reduces frequency and severity
• Physical therapy: For cervicogenic component
• Limit caffeine intake: Avoid rebound
• Avoid hormonal triggers: Consider alternative contraception in women with hormonal migraines

---

8. Acute (Abortive) Treatment

Key Principles:

• Treat as early as possible in the attack - once the attack is fully established, oral drugs are less effective due to reduced GI motility and poor absorption
• Use non-oral routes (intranasal, SC injection, rectal) if severe nausea/vomiting is present
• Stratified care is superior to step care: match drug potency to attack severity upfront (randomized trial evidence) rather than always starting NSAIDs first
• Rational polytherapy (combining agents with different mechanisms - e.g., NSAID + triptan + antiemetic) is more effective than monotherapy
• Bradley and Daroff's Neurology, p. 350

Step 1: Mild-to-Moderate Attacks

• Bradley and Daroff's Neurology (Table 102.4)

Step 2: Moderate-to-Severe Attacks - Triptans (Drug of Choice)

• Begin as soon as possible after headache onset (NOT during aura - sumatriptan SC may be ineffective in the aura phase)
• Not for use in prophylaxis - acute treatment ONLY
• Contraindicated in: hemiplegic migraine, basilar/brainstem migraine, uncontrolled hypertension, ischemic heart disease, Prinzmetal's angina, history of stroke/TIA, pregnancy (relative)
• Not effective if taken during aura (controversy exists)

Step 3: Ergot Derivatives (Alternative to Triptans)

Step 4: Antiemetics / Adjuncts

Step 5: CGRP Receptor Antagonists - Gepants (Newer Acute Agents)

• No vasoconstriction → safe in cardiovascular disease
• Safe in hemiplegic/basilar migraine
• Rimegepant can serve dual purpose (acute + prevention)

Step 6: Ditans (5-HT1F Agonists)

• No vasoconstriction → cardiovascular safety
• Oral: 50-200 mg as needed
• Side effects: dizziness, sedation (CNS-active); driving restriction for 8 hours after use

Special Situation: Status Migrainosus (>72 hours)

• IV fluids (rehydration if vomiting)
• IV prochlorperazine or chlorpromazine (first-line in ED)
• IV ketorolac 15-30 mg q6h (parenteral NSAID)
• IV dihydroergotamine (DHE) - highly effective; pretreat with metoclopramide for nausea
• IV dexamethasone 4-8 mg (single dose - reduces recurrence within 24-72 hours)
• IV magnesium sulfate 1-2 g (particularly useful in migraine with aura)
• Opioids: AVOID if possible - risk of rebound headache and habituation; reserved for when all else fails

Intranasal Lidocaine

---

9. Prophylactic (Preventive) Treatment

Indications for Prophylaxis:

• ≥4 migraine days/month OR attacks so severe that acute treatment is consistently insufficient
• Increasing frequency over time / possible medication overuse
• Acute therapy overuse (risk of rebound/medication overuse headache - MOH)
• Chronic migraine (≥15 headache days/month with ≥8 being migraine)
• Specific migraine subtypes: hemiplegic migraine, migraine with prolonged aura, migrainous infarction
• Patient preference / significant disability

Class 1: Beta-Blockers (Best Evidence - First Line)

Class 2: Antiepileptic Drugs (Level A Evidence)

Class 3: Antidepressants

Class 4: Calcium Channel Blockers

Class 5: OnabotulinumtoxinA (Botox) - For Chronic Migraine

• FDA approved specifically for chronic migraine (≥15 headache days/month)
• 155-195 units injected across 31-39 sites in head and neck muscles every 12 weeks
• Very effective for chronic migraine; not indicated for episodic migraine
• Mechanism: Inhibits CGRP and SP release from peripheral trigeminal afferents

Class 6: CGRP Monoclonal Antibodies (Newest - Most Targeted Therapy)

• Harrison's 22e; Goldman-Cecil Medicine; Kaplan & Sadock's Psychiatry

Summary Table: Prophylactic Agents with Evidence Levels

• Textbook of Family Medicine 9e; Kaplan & Sadock's Psychiatry (Table 2.11-5)

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10. Special Situations

Menstrual Migraine

• Occurs perimenstrually (day -2 to +3 of menstruation)
• Short-term prophylaxis (when regular prophylaxis is not desired):
  • NSAIDs: Naproxen sodium 550 mg BID (days -3 to +3) OR mefenamic acid 250 mg TID OR ketoprofen 75 mg TID
  • Frovatriptan or naratriptan (longer-acting triptans) taken days -3 to +3 - specifically recommended for menstrual migraine prevention
  • Ergots (days -3 to +3) - alternative
• Hormonal approaches: Transdermal estrogen supplementation during menses; changing to continuous OCP without pill-free intervals

Migraine in Pregnancy

• Triptans: Use with caution (Category C); sumatriptan has most safety data
• Ergotamine: Contraindicated (fetal vasoconstriction/harm)
• Valproate: Contraindicated (teratogenic)
• Safe options: Paracetamol, beta-blockers (propranolol), low-dose aspirin, magnesium
• Migraine often improves in the 2nd and 3rd trimesters due to stable estrogen levels

Medication Overuse Headache (MOH / Rebound Headache)

• Develops with regular use of acute medications >10-15 days/month
• Worst with opioids and butalbital (>10 days/month); also triptans and ergotamines (>10 days/month); NSAIDs (>15 days/month)
• Management: Withdrawal of overused medication + bridging therapy (NSAIDs, corticosteroids, DHE) + initiate prophylaxis

---

11. Stepped Approach Summary

ACUTE MIGRAINE ATTACK
         |
   Mild-Moderate?
         |
   Yes → NSAIDs ± antiemetic ± caffeine combination
         |
   Insufficient → TRIPTAN (oral/nasal/SC based on severity/nausea)
         |
   + Antiemetic (metoclopramide / prochlorperazine) if nausea
         |
   Refractory/Severe → DHE IV or SC + antiemetic
         |
   Status migrainosus → ED: IV prochlorperazine + ketorolac ± DHE ± dexamethasone
         |
   No vascular risk? → Gepants (ubrogepant/rimegepant) or lasmiditan as alternatives

PROPHYLAXIS (if ≥4 attacks/month):
   First-line → Propranolol OR topiramate OR amitriptyline
   Refractory/chronic → Add OnabotulinumtoxinA (if chronic migraine)
   Or switch to → CGRP monoclonal antibody (erenumab/fremanezumab/galcanezumab)

---

Recent Evidence Alert (2025): European evidence-based guidelines (Ornello et al., Cephalalgia 2025, PMID 40277319/40277321) confirm CGRP-targeted therapies (both gepants and monoclonal antibodies) as effective first-line options for both acute and preventive treatment. A 2024 network meta-analysis (Karlsson et al., BMJ, PMID 39293828) comparing acute migraine drugs found triptans remain the most effective class for acute treatment overall.

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Quick Summary of All Answers

• ACS = UA + NSTEMI + STEMI spectrum; caused by plaque rupture → thrombosis
• Pathogenesis: Atherosclerosis → vulnerable plaque → rupture → platelet activation → thrombosis → ischemia/infarction
• Clinical: Crushing central chest pain >20 min, radiation, diaphoresis, dyspnea
• Emergency Rx: MONA + Aspirin 300 mg + P2Y12 inhibitor + STEMI → Primary PCI within 90 min / NSTEMI → Anticoagulation + early angiography + beta-blocker + high-dose statin

• Diagnosis: Spontaneous Bacterial Peritonitis (SBP) complicating decompensated cirrhosis (SAAG ≥1.1 + PMN ≥250 cells/mm³ = SBP)
• Evaluation: LFTs, viral markers, ultrasound Doppler, endoscopy, ascitic culture, Child-Pugh/MELD
• Management: Cefotaxime IV + IV albumin (Day 1: 1.5 g/kg, Day 3: 1 g/kg) + diuretics + SBP prophylaxis with norfloxacin