*MGUS: Monoclonal Gammopathy of Unknown Significance

Allopurinol is first-line urate-lowering agent. We switch to febuxostat only if the patient can't tolerate allopurinol or if it's contraindicated (as in CKD where its dose must be adjusted). Also, remember that Febuxostat increases cardiovascular and all-cause mortality.

Calcium physiology (including PTH, vitamin D, and calcitonin)

⚡ Management of a Seizure (Fit)

1. Immediate (Acute seizure)
• Airway, Breathing, Circulation (ABC) → Ensure patent airway, give O₂ if needed.
• Position: Place patient on the side (recovery position) to avoid aspiration.
• IV access, monitor vitals, blood sugar.
• If seizure >5 min (status epilepticus starting):
• First-line: IV/rectal benzodiazepine (Diazepam, Lorazepam, or Midazolam).
• If no response → IV phenytoin/fosphenytoin (or phenobarbital).
• If still refractory → PICU/ICU for midazolam infusion / anesthesia support.

First-line (Benzodiazepines)
• Diazepam IV/rectal: 0.2–0.5 mg/kg (max 10 mg per dose). May repeat once after 10 min.
• Lorazepam IV: 0.1 mg/kg (max 4 mg per dose). Can repeat after 10–15 min.
• Midazolam IV/IM/buccal/intranasal: 0.2 mg/kg (max 10 mg per dose).

Second-line (if no response to benzo)
• Phenytoin IV (or Fosphenytoin): 15–20 mg/kg (give slowly, monitor ECG & BP).
• Phenobarbital IV: 15–20 mg/kg loading dose.

If seizure continues (>10–15 min):
• Repeat benzodiazepine (once).
• Then give IV phenytoin (15–20 mg/kg) OR valproate (20–40 mg/kg) OR levetiracetam (40–60 mg/kg).

Refractory” seizure (or refractory status epilepticus) means the fit does not stop even after giving:
1. Two adequate doses of first-line drugs (benzodiazepines), and
2. A dose of a second-line antiepileptic (like phenytoin, valproate, or levetiracetam).

When a seizure is refractory (doesn’t stop after benzodiazepines + a second-line antiepileptic), the patient must go to the ICU because stronger continuous anesthetic drugs are needed.

Examples:
• Midazolam infusion
• Propofol infusion
• Thiopental (barbiturate) infusion

These medicines put the brain into a controlled coma to stop electrical activity. Because they suppress breathing, the patient usually needs intubation and mechanical ventilation with close monitoring of blood pressure and brain function (EEG).

Calcium (Ca²⁺)
• Hypocalcemia (total Ca²⁺ < 8.5 mg/dL / ionized < 1.1 mmol/L):
• Tetany, muscle spasms, laryngospasm, seizures.

Calcium gluconate 10% → 1–2 mL/kg IV slowly over 10 minutes (max ~10 ).
• Monitor ECG during infusion (risk of arrhythmia).
• If symptoms persist → can repeat.

Always give slow IV (never IM or SC) → risk of tissue necrosis.
• Continuous cardiac monitoring during infusion (arrhythmia risk).
• If fits continue → repeat dose or start infusion.
• Treat underlying cause (vitamin D deficiency, hypoparathyroidism, hypomagnesemia, renal disease).

Hypokalemia and Hypocalcemia
1. Hypokalemia causes metabolic alkalosis
• Low K⁺ shifts H⁺ ions into cells → blood becomes more alkaline.
• This is called a contraction alkalosis.
2. Alkalosis increases calcium binding to albumin
• In alkalosis, albumin has more negative charges → it binds more calcium.
• This lowers the amount of free ionized Ca²⁺ (the biologically active form).
3. Ionized calcium falls, total calcium may remain normal
• So, even if lab “total calcium” looks okay, the patient develops symptomatic hypocalcemia (tetany, seizures, paresthesias).

Causes of Hypocalcemia

1. Neonatal & Pediatric Causes
• Prematurity (immature parathyroid response)
• Vitamin D deficiency / rickets
• Hypoparathyroidism (congenital or post-surgical)
• Hypomagnesemia (impairs PTH release/action)
• High phosphate load (e.g., cow’s milk in infants, tumor lysis, renal failure)

2. Systemic / Adult Causes
• Hypoparathyroidism (autoimmune, surgical, genetic)
• Vitamin D deficiency or resistance (CKD, malabsorption, anticonvulsant therapy)
• Chronic kidney disease (↓ 1α-hydroxylase activity → ↓ calcitriol)
• Pancreatitis (fat saponification traps calcium)
• Massive blood transfusion (citrate binds calcium)

3. Electrolyte-related Causes
• Hypomagnesemia (↓ PTH secretion, ↓ bone response)
• Alkalosis (↑ Ca²⁺ binding to albumin → ↓ ionized calcium)

The classical triad of congenital toxoplasmosis is:
1. Chorioretinitis
2. Hydrocephalus
3. Intracranial calcifications (classically diffuse, especially basal ganglia)

Presence of this triad strongly suggests congenital toxoplasmosis, although not all infants present with all three.

Transplacental (Congenital) Varicella Infection

Limb Hypoplasia
• Underdeveloped or shortened extremities.
• Caused by viral damage to fetal blood vessels and nerves.
2. Cutaneous Scars
• Linear, cicatricial scars on the skin, often along dermatomes.
• Appear like burn or surgical scars, present at birth.
• Pathognomonic for transplacental varicella infection.

Prenatal infection,
Classical clinical features:
1. Skin → cicatricial skin scars (burn-like, linear or zig-zag).
2. Limbs → limb hypoplasia or underdeveloped extremities.
3. Central Nervous System → microcephaly, seizures, cortical atrophy, developmental delay.
4. Eyes → cataracts, chorioretinitis, microphthalmia, nystagmus.
5. Growth → intrauterine growth restriction (IUGR), low birth weight.

Reactivation of Congenital Varicella (Shingles in children)
• If a fetus is infected with varicella-zoster virus (VZV) in utero, the virus remains latent in the sensory ganglia.
• Later in childhood, the virus can reactivate as herpes zoster (shingles), even in very young children.
• Unlike adults, shingles in these children may occur without a history of chickenpox (since their “primary infection” was congenital).
• Reactivation usually causes:
• Dermatomal vesicular rash (localized to a single dermatome).
• Neuropathic pain (less severe in children than adults).
• May be associated with eye complications if the trigeminal ganglion is involved.

For Congenital Varicella Syndrome, the Central Nervous System (CNS) features mainly include:
• Microcephaly (small head size due to poor brain development).
• Seizures (from cortical scarring/atrophy).
• Cortical atrophy (loss of brain tissue).
• Developmental delay / intellectual disability.