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USMLE Step 2 CS Minicases – Complete Clinical Casebook with Differential Diagnosis & Workups | Case Scenarios (2025 Edition).

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This document compiles complete USMLE Step 2 CS minicases, covering full clinical presentations, differential diagnoses, and essential workup steps. It includes high-yield vignettes from all core disciplines including neurology, psychiatry, internal medicine, OB/GYN, pediatrics, ENT, and infectious disease. Each case follows the format expected on Step 2 CS or shelf OSCEs, with realistic chief complaints, DDx lists, and lab/imaging suggestions. Perfect for students looking to master the CS structure, clinical reasoning, and workup approach, this is the ultimate companion for clinical skills, Step 2 prep, and NBME shelf review.

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,USMLE Step 2 CS Minicases – Complete Clinical
Casebook with Differential Diagnosis &
Workups | Case Scenarios (2025 Edition).
21 yo F presents with several episodes of
throbbing left temporal pain that lasts
for 2-3 hours. Prior to its onset, she sees
fl ashes of light in her right visual fi eld
and feels weakness and numbness on the
right side of her body for a few minutes.
Headaches are often associated with
nausea and vomiting. She has a family
history of migraine.

Migraine (complicated)
Tension headache
Cluster headache
Pseudotumor cerebri
Trigeminal neuralgia
CNS vasculitis
Partial seizure
Intracranial neoplasm

CBC
ESR
CT—head
MRI—brain
LP

26 yo M presents with severe right
temporal headaches associated with
ipsilateral rhinorrhea, eye tearing, and
redness. Episodes have occurred at the
same time every night for the past week
and last for 45 minutes.

Cluster headache
Migraine
Tension headache
Sinusitis
Pseudotumor cerebri
Trigeminal neuralgia
Intracranial neoplasm

,CBC
ESR
CT—head
MRI—brain
LP

65 yo F presents with severe, intermittent
right temporal headache, fever, blurred
vision in her right eye, and pain in her
jaw when chewing.

Temporal arteritis (giant cell
arteritis)
Migraine
Cluster headache
Tension headache
Meningitis
Carotid artery dissection
Pseudotumor cerebri
Trigeminal neuralgia
Intracranial neoplasm

CBC
ESR
CRP
Temporal artery biopsy
Doppler U/S—carotid
MRI—brain

30 yo F presents with frontal headache,
fever, and nasal discharge. There is pain
on palpation of the frontal and maxillary
sinuses. She has a history of sinusitis.

Sinusitis
Migraine
Tension headache
Meningitis
Intracranial neoplasm

CBC
XR—sinus
CT—sinus
LP

, 50 yo F presents with recurrent episodes
of bilateral squeezing headaches that
occur 3-4 times a week, typically
toward the end of her work day. She is
experiencing signifi cant stress in her life.

Tension headache
Migraine
Depression
Caffeine or analgesic
withdrawal
Hypertension
Cluster headache
Pseudotumor cerebri
Intracranial neoplasm

CBC
Electrolytes
ESR
CT—head
LP

35 yo M presents with sudden severe
headache, vomiting, confusion, left
hemiplegia, and nuchal rigidity.

DDX:
1 - Subarachnoid hemorrhage
2 - Migraine
3 - Meningitis/encephalitis
4 - Intracranial hemorrhage
5 - Intracranial neoplasm, vertebral a. dissection, intracranial venous thrombosis, acute htn

W/U:
1 - CBC, PT/PTT, CT head w/o contrast, MRI/MRA brain
3 - LP

25 yo M presents with high fever, severe
headache, confusion, photophobia, and
nuchal rigidity. Kernig's and Brudzinski's
signs are positive.

Meningitis
Migraine
Subarachnoid hemorrhage
Sinusitis/encephalitis
Intracranial or epidural abscess
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