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 3-year-old girl is brought to the emergency room because of a 5-day history of high fever and fatigue. During this time she has been crying more than usual and eating less. Her mother says that the child has also complained about pain in her arms and legs for the past 3 days. She was born at term and has been otherwise healthy. She appears ill. Her temperature is 39.5°C (103.1°F), pulse is 128/min, and blood pressure is 96/52 mm Hg. The lungs are clear to auscultation. A grade 3/6 systolic murmur is heard at the apex. There is mild tenderness to palpation of the left upper quadrant with no guarding or rebound. The spleen is palpated 3 cm below the left costal margin. There is no redness or swelling of the joints. Laboratory studies show: Hemoglobin 11.8 g/dL Leukocyte count 16,300/mm3 Platelet count 220,000/mm3 Erythrocyte sedimentation rate 50 mm/h Serum Glucose 96 mg/dL Creatinine 1.7 mg/dL Total bilirubin 0.4 mg/dL AST 18 U/L ALT 20 U/L Urine Protein 2+ RBC casts rare RBC 10/hpf WBC 1–2/hpf Which of the following is the most appropriate next step in management?

Obtain 3 sets of blood cultures

Obtain a transesophageal echocardiography

Administer intravenous vancomycin

A 32-year-old woman presents with a 3-month history of intermittent blurred vision and problems walking. The patient states that she often feels “pins and needles” in her legs that cause her problems when she’s walking. The patient is afebrile, and her vital signs are within normal limits. An autoimmune disorder is suspected. Which of the following findings would most likely be present in this patient?

Damaged myelin sheath and myelin-producing cells

Destruction of blood-brain barrier

Degeneration of anterior horn cells

Decreased cerebrospinal fluid due to destruction of cells

A 3-year-old boy is brought to the physician for the evaluation of recurrent skin lesions. The episodes of lesions started at the age of 3 months. He has also had several episodes of respiratory tract infections, enlarged lymph nodes, and recurrent fevers since birth. The boy attends daycare. The patient's immunizations are up-to-date. He is at the 5th percentile for length and 10th percentile for weight. He appears ill. Temperature is 38°C (100.4°F). Examination shows several raised, erythematous lesions of different sizes over the face, neck, groin, and extremities; some are purulent. Bilateral cervical and axillary lymphadenopathy are present. What is the most likely underlying mechanism of this patient's symptoms?

Defective cytoplasmic tyrosine kinase

Impaired signaling to actin cytoskeleton reorganization

Defective neutrophil chemotaxis

Impaired repair of double-strand DNA breaks

Central nervous system infections for USMLE Step 2 CK: High-Yield Pediatrics Lessons

CNS Infections - Brain Under Siege

Meningitis: Inflammation of meninges (fever, headache, nuchal rigidity).
Encephalitis: Inflammation of brain parenchyma (altered sensorium, seizures, focal deficits).
Meningoencephalitis: Overlap of both meningitis and encephalitis.
Brain Abscess: Focal, encapsulated infection within parenchyma; presents with fever, focal signs, and features of raised ICP. Ring-enhancing lesions on imaging.

Brain Anatomy and Barriers in CNS Infections

⭐ In Tuberculous Meningitis, CSF classically shows a spider-web coagulum (fibrin clot) on standing, with markedly elevated protein and lymphocytic pleocytosis.

Bacterial Meningitis - The Pus Peril

CSF Analysis: Crucial for diagnosis.

Feature	Bacterial	Viral	Tubercular (TBM)	Fungal
Appearance	Turbid/Purulent	Clear	Cobweb, Fibrin web	Viscous, Clear
Cells (/μL)	>1000 (↑↑ PMNs)	<1000 (↑ Lympho)	100-500 (↑ Lympho)	<500 (↑ Lympho)
Protein	↑↑ (>100 mg/dL)	N / ↑	↑↑ (>150 mg/dL)	↑
Glucose	↓↓ (<40 mg/dL)	Normal	↓ (<45 mg/dL)	↓

-   **Neonate (<1 mo):** *E. coli*, Group B Strep, *Listeria*. (📌 **GEL**)
-   **1 mo - 5 yr:** *S. pneumoniae*, *N. meningitidis*, *H. influenzae*.
-   **>5 yrs:** *S. pneumoniae*, *N. meningitidis*.

⭐ Dexamethasone (0.15 mg/kg) is given before or with the first antibiotic dose in children >6 weeks to reduce sensorineural hearing loss, especially in Hib & pneumococcal meningitis.

Empirical Antibiotic Therapy Flowchart:

TB Meningitis - The Slow Burn

Onset: Insidious, subacute progression over 2-8 weeks. Prodrome of low-grade fever, malaise, headache.
Staging (MRC): Stage 1 (Alert), Stage 2 (Lethargic, CN palsies), Stage 3 (Coma, seizures).
CSF Analysis: Classic triad of ↑ lymphocytes, ↑↑ protein (>100 mg/dL), ↓ glucose (<45 mg/dL). Fibrin web / cobweb coagulum on standing.
Imaging (CT/MRI): Basal exudates, hydrocephalus, tuberculomas, infarcts.
Treatment: Anti-tubercular therapy (ATT) + corticosteroids (prednisolone) to reduce inflammation.

⭐ High-Yield: Thick, gelatinous exudates at the base of the brain are pathognomonic, leading to cranial nerve palsies (esp. VI) and obstructive hydrocephalus.

CT scans showing progression of TB meningitis

Viral Infections - Ghost In The Machine

Aseptic Meningitis: Most common viral CNS infection. Predominantly caused by Enteroviruses (Coxsackie, Echovirus) and Mumps.
- CSF: Lymphocytic pleocytosis, normal glucose, sterile on bacterial culture.
Encephalitis: Inflammation of the brain parenchyma.

Feature	Herpes Simplex Encephalitis (HSV-1)	Japanese Encephalitis (JE)
Clinical	Acute fever, focal seizures, altered sensorium	Parkinsonian rigidity, tremors, mask-like facies
CSF	↑ RBCs, lymphocytic pleocytosis	Similar to aseptic meningitis
Imaging	Temporal lobe hemorrhagic necrosis	Thalamic, basal ganglia involvement

MRI brain: Herpes simplex encephalitis

Neonatal Meningitis - A Fragile Start

Common Pathogens: Group B Strep (S. agalactiae), E. coli, Listeria monocytogenes. 📌 Mnemonic: GEL.
Clinical Signs: Non-specific and subtle. Includes fever/hypothermia, poor feeding, lethargy, irritability, seizures, or a tense, bulging fontanelle.
Empirical Treatment: Ampicillin (for Listeria) + Gentamicin (synergy) OR Cefotaxime (better CNS penetration).

⭐ In late-onset meningitis (after 72 hours), Staphylococcus and gram-negatives are more common; consider Vancomycin.

Neonatal meningitis is caused by GBS, E. coli, & Listeria. In infants/children, it's S. pneumoniae.

Bacterial CSF: ↑ neutrophils, ↑ protein, ↓ glucose. Viral CSF: ↑ lymphocytes, normal glucose.

Tuberculous meningitis: Lymphocytic CSF, markedly ↑ protein, ↓ glucose, and cobweb coagulum.

HSV encephalitis causes hemorrhagic necrosis of the temporal lobes; treat with IV Acyclovir.

Japanese Encephalitis shows extrapyramidal features and bilateral thalamic lesions.

Dexamethasone is vital in Hib meningitis to prevent sensorineural hearing loss.

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