A 15-year-old boy is brought to the Emergency department by ambulance from school. He started the day with some body aches and joint pain but then had several episodes of vomiting and started complaining of a terrible headache. The school nurse called for emergency services. The boy was born at 39 weeks gestation via spontaneous vaginal delivery. He is up to date on all vaccines and is meeting all developmental milestones. Past medical history is noncontributory. He is a good student and enjoys sports. At the hospital, his blood pressure is 120/80 mm Hg, heart rate is 105/min, respiratory rate is 21/min, and his temperature is 38.9°C (102.0°F). On physical exam, he appears drowsy with neck stiffness and sensitivity to light. Kernig’s sign is positive. An ophthalmic exam is performed followed by a lumbar puncture. An aliquot of cerebrospinal fluid is sent to microbiology. A gram stain shows gram-negative diplococci. A smear is prepared on blood agar and grows round, smooth, convex colonies with clearly defined edges. Which of the following would identify the described pathogen?

Oxidase-positive and ferments glucose and maltose

Oxidase-positive test and ferments glucose only

Catalase-negative and oxidase-positive

No growth on Thayer-Martin medium

A 65-year-old patient presents with rapidly progressive dementia, myoclonus, and ataxia over 3 months. Laboratory studies, including serum vitamin B12 (cyanocobalamin), thyroxine (T4), and thyroid-stimulating hormone concentrations, are within normal limits. A lumbar puncture is performed. Cerebrospinal fluid (CSF) analysis is most likely to show which of the following?

Increased 14-3-3 protein concentration

Anti-glutamic acid decarboxylase antibodies

Increased α-synuclein protein concentration

A 67-year-old man presents to the emergency department with confusion. The patient is generally healthy, but his wife noticed him becoming progressively more confused as the day went on. The patient is not currently taking any medications and has no recent falls or trauma. His temperature is 102°F (38.9°C), blood pressure is 126/64 mmHg, pulse is 120/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for a confused man who cannot participate in a neurological exam secondary to his confusion. No symptoms are elicited with flexion of the neck and jolt accentuation of headache is negative. Initial laboratory values are unremarkable and the patient's chest radiograph and urinalysis are within normal limits. An initial CT scan of the head is unremarkable. Which of the following is the best next step in management?

CT angiogram of the head and neck

Vancomycin, ceftriaxone, ampicillin, and dexamethasone

A 35-year-old woman presents with headaches and seizures. MRI shows a well-circumscribed, calcified frontal lobe mass. Histology reveals oligodendroglioma with 1p/19q codeletion and IDH1 mutation. She undergoes gross total resection. Two years later, surveillance MRI shows a new enhancing nodule at the resection margin. Biopsy shows increased mitotic activity, microvascular proliferation, and retained 1p/19q codeletion but new CDKN2A/B homozygous deletion. What is the most critical factor in determining management strategy?

Retained 1p/19q codeletion predicts continued chemosensitivity to PCV regimen

The tumor has progressed to anaplastic oligodendroglioma requiring combined chemoradiation with temozolomide and RT

CDKN2A/B deletion indicates transformation to glioblastoma requiring maximal therapy

Loss of IDH1 mutation suggests new primary tumor requiring re-resection only

Microvascular proliferation mandates anti-angiogenic therapy with bevacizumab

CNS infections for USMLE Step 2 CK: High-Yield Pathology Lessons

Meningitis - Brain's Fiery Blanket

Meningitis is inflammation of the leptomeninges (arachnoid and pia mater). Diagnosis hinges on cerebrospinal fluid (CSF) analysis from a lumbar puncture, which reveals the causative agent's footprint.

Lumbar Puncture for CSF Sample Collection

CSF Analysis Findings:

Characteristic	Bacterial	Viral	Fungal/TB
Opening Pressure	↑↑	Normal / ↑	↑
Cell Type	↑ Neutrophils (>1000/μL)	↑ Lymphocytes (<500/μL)	↑ Lymphocytes
Protein	↑ (>100 mg/dL)	Normal / ↑ (<100 mg/dL)	↑
Glucose	↓↓ (<40 mg/dL or <0.4 serum)	Normal	↓

Encephalitis - When Neurons Rage

Direct inflammation of brain parenchyma, primarily affecting neurons, leading to cerebral dysfunction.
Etiologies & Features:
- HSV-1: Most common cause of fatal sporadic encephalitis; temporal lobe necrosis.
- Arboviruses: (e.g., West Nile, St. Louis) - transmitted by mosquitoes; seasonal outbreaks.
- Rabies: Rhabdovirus from animal bites; hydrophobia, Negri bodies (intracytoplasmic inclusions).
Diagnosis: CSF analysis (lymphocytic pleocytosis, ↑ protein), PCR for viral DNA, and brain MRI.

⭐ In HSV-1 encephalitis, look for personality changes (due to frontal/temporal lobe involvement) like hypomania or bizarre behavior. Treatment with acyclovir should not be delayed pending diagnostic confirmation.

Focal Lesions - Abscesses & Parasites

Brain Abscess
- Etiology: Bacterial (Staphylococcus aureus, Viridans streptococci) or fungal. Spread via direct extension (sinusitis, otitis) or hematogenously (endocarditis).
- Phases: Early cerebritis (inflammation) → Late cerebritis (liquefactive necrosis) → Fibrous capsule formation.
- Imaging: Ring-enhancing lesion on CT/MRI with contrast.
Parasitic Infections
- Toxoplasmosis (Toxoplasma gondii)
  - Risk: Reactivation in immunosuppressed patients (AIDS, CD4 < 100 cells/mm³).
  - Imaging: Multiple ring-enhancing lesions, often in basal ganglia.
- Neurocysticercosis (Taenia solium larvae)
  - Transmission: Ingestion of eggs (fecal-oral).
  - Presentation: New-onset seizures are classic.
  - Imaging: "Swiss cheese" appearance; cysts in various stages (viable, calcified).

⭐ In an HIV+ patient with multiple ring-enhancing brain lesions, the main differential is Toxoplasmosis vs. Primary CNS Lymphoma. A trial of pyrimethamine and sulfadiazine is diagnostic and therapeutic.

MRI Brain: Ring-enhancing lesions in CNS infections

Prion Disease - The Folded Killers

Pathogenesis: Misfolded prion protein (PrPsc) induces a conformational change in the normal cellular protein (PrPc), causing aggregation.
Histopathology: Leads to spongiform encephalopathy-vacuolation in the neuropil, neuronal loss, and gliosis, but no inflammation.
Creutzfeldt-Jakob Disease (CJD):
- Presents with rapidly progressive dementia and myoclonus.
- CSF may show ↑ 14-3-3 protein.

⭐ Iatrogenic CJD is transmissible through contaminated neurosurgical instruments, dura mater grafts, or corneal transplants.

High‑Yield Points - ⚡ Biggest Takeaways

Bacterial meningitis CSF shows ↑ neutrophils, ↑ protein, and ↓ glucose; viral meningitis CSF has ↑ lymphocytes with normal glucose.

HSV-1 is the most common cause of fatal sporadic encephalitis, with classic temporal lobe involvement.

Brain abscesses and Toxoplasmosis both present as ring-enhancing lesions on imaging, but Toxoplasmosis is more common in HIV/AIDS.

JC virus causes Progressive Multifocal Leukoencephalopathy (PML) in the immunocompromised.

Prion diseases (e.g., CJD) lead to rapidly progressive dementia and spongiform encephalopathy.

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CNS infections