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Neonatal Seizures - O.P. Ghai Essential Pediatrics 10th Edition

Definition

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Incidence

• 1-5 per 1,000 live births (term neonates)
• 10-130 per 1,000 in preterm/VLBW neonates
• Most common neurological emergency in the newborn

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Classification (Volpe's Classification - as used in Ghai)

1. Subtle Seizures (most common, ~50%)

• More common in preterm infants
• Manifestations:
  • Ocular: tonic horizontal eye deviation, sustained eye opening, blinking, nystagmus
  • Oral-buccal-lingual: sucking, chewing, drooling, lip smacking
  • Limb: "cycling" or "pedaling" movements of legs, "rowing/swimming" movements of arms
  • Autonomic: apnea, tachycardia, BP changes, flushing, pupillary changes
• Most subtle seizures are NOT associated with EEG correlate - they may represent brainstem release phenomena

2. Clonic Seizures

• Focal clonic: Rhythmic jerking (1-3/sec) of one extremity or one side of the face/body; infant is usually conscious; strongly associated with EEG correlate; most often due to focal cerebral infarction
• Multifocal clonic: Clonic movements in multiple limbs, migrate randomly (not Jacksonian); common in metabolic disturbances (hypocalcemia, hyponatremia)

3. Tonic Seizures

• Focal tonic: Sustained posturing of a limb or asymmetric posturing of trunk/neck; EEG correlate often present
• Generalized tonic: Extension of all limbs (decerebrate) or flexion of arms + extension of legs (decorticate); poor EEG correlation - represents brainstem release; associated with severe HIE, IVH; poor prognosis

4. Myoclonic Seizures (least common)

• Focal: Single or multiple jerks of one limb; variable EEG correlation
• Multifocal: Asynchronous jerks of multiple limbs
• Generalized: Bilateral, synchronous flexion jerks; may represent early infantile epileptic encephalopathy (Ohtahara syndrome); worst prognosis

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Etiology (Mnemonic: HHIMMSST)

By Timing:

By Frequency:

1. Hypoxic-Ischemic Encephalopathy (HIE) - ~60% of all neonatal seizures; most common cause; seizures typically begin 6-24 hours after birth
2. Intracranial hemorrhage - IVH (preterm), SAH (term), SDH; ~15%
3. Metabolic causes (~15%)
   • Hypoglycemia (BG <45 mg/dL) - presents Day 1-2, especially in IDM, SGA, LGA
   • Hypocalcemia (<7 mg/dL total; <4.4 mg/dL ionized) - early (Day 2-3, sick neonates) vs late (Day 5-7, associated with cow milk formula/hyperphosphatemia)
   • Hypomagnesemia (<0.6 mmol/L) - often accompanies hypocalcemia
   • Hyponatremia (<120 mEq/L) or Hypernatremia
   • Hyperbilirubinemia (kernicterus)
4. Infection - bacterial meningitis, viral encephalitis (HSV), TORCH infections
5. Developmental brain defects - lissencephaly, pachygyria, polymicrogyria
6. Inborn errors of metabolism - pyridoxine dependency (ALDH7A1), maple syrup urine disease, non-ketotic hyperglycinemia
7. Drug withdrawal - maternal opiate/benzodiazepine use
8. Benign neonatal seizures - familial (KCNQ2/KCNQ3) and non-familial ("fifth-day fits" - Day 4-6, benign, no recurrence)

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Clinical Features / Diagnosis

Differentiation from Jitteriness

Investigations

1. Bedside glucose (immediate)
2. Serum electrolytes: Na, K, Ca, Mg, phosphorus
3. CBC, blood culture
4. Lumbar puncture (if infection suspected): CSF cell count, protein, glucose, culture
5. Blood gas, serum bilirubin, LFT, ammonia
6. Cranial ultrasound (initial imaging - for IVH)
7. CT head (for structural, hemorrhage - if ultrasound inconclusive)
8. MRI brain (preferred for HIE, cortical dysplasia - when stable)
9. EEG - gold standard for confirmation; also for monitoring treatment response
10. TORCH titers, urine metabolic screen (if etiology unclear)

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Treatment

Step 1 - Stabilization (ABCs)

• Ensure airway, breathing, circulation
• Treat immediately identifiable causes:
  • Hypoglycemia: IV dextrose 10% - 2 mL/kg bolus
  • Hypocalcemia: IV calcium gluconate 10% - 2 mL/kg (slowly, with cardiac monitoring)
  • Hypomagnesemia: IV/IM magnesium sulfate 50% - 0.2 mL/kg
  • Pyridoxine dependency: IV pyridoxine 100 mg (diagnostic + therapeutic)

Step 2 - Antiepileptic Drugs (AED)

• Phenobarbitone (Phenobarbital) - 20 mg/kg IV (loading dose); give over 15-20 min
  • Can give additional 10 mg/kg boluses up to total 40 mg/kg
  • Maintenance: 3-5 mg/kg/day (after 24 hours)

• Phenytoin - 20 mg/kg IV at ≤1 mg/kg/min; maintenance 4-8 mg/kg/day
  • Fosphenytoin preferred if available (safer)

• Midazolam - 0.05-0.15 mg/kg IV bolus, then infusion 0.1-0.4 mg/kg/hr
• Levetiracetam - 20-30 mg/kg IV (increasingly used, especially in HIE)
• Lorazepam - 0.05-0.1 mg/kg IV
• Clonazepam, Lidocaine (in some protocols)

Summary of Drug Sequence (Ghai approach):

Phenobarbitone (first choice)
        ↓ (if no response)
Phenytoin (second choice)
        ↓ (if no response)
Benzodiazepines (lorazepam/midazolam)
        ↓ (if no response)
Pyridoxine (if metabolic etiology suspected)
        ↓ (if no response)
Levetiracetam / Clonazepam

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Prognosis

• Underlying etiology is the most important determinant
• Seizures due to HIE: 50% develop cerebral palsy, intellectual disability, or epilepsy
• Generalized tonic and myoclonic seizures: worse prognosis
• Abnormal background EEG (burst suppression): poor prognosis
• Seizures persisting beyond the neonatal period

• Hypocalcemia-related seizures
• Benign neonatal convulsions (familial and non-familial "fifth-day fits")
• SAH without parenchymal injury

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Specific Conditions (Ghai highlights)

Pyridoxine-Dependent Seizures

• Rare autosomal recessive (ALDH7A1 gene)
• Refractory seizures unresponsive to AEDs
• Dramatic response to IV pyridoxine 100 mg
• Maintenance: pyridoxine 15-30 mg/kg/day orally lifelong

Benign Neonatal Convulsions ("Fifth-Day Fits")

• Onset Day 4-6 of life
• Clonic, multifocal, brief episodes
• No specific etiology found
• Spontaneous remission within 1-2 weeks
• Familial type: autosomal dominant, KCNQ2/KCNQ3 mutations

Early Neonatal Myoclonic Encephalopathy (Aicardi syndrome / Ohtahara syndrome)

• Onset in first weeks
• Burst-suppression EEG pattern
• Catastrophic epilepsy, poor outcome

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Key Points for Exam (Ghai-style)

• HIE = most common cause of neonatal seizures
• Phenobarbitone = first-line AED for neonatal seizures
• "Fifth-day fits" = benign, Day 4-6, clonic, good prognosis
• EEG = gold standard for diagnosis
• Jitteriness is stimulus-sensitive and suppressible - NOT a seizure
• Hypocalcemia late (Day 5-7) = cow milk formula (high phosphate load)
• Pyridoxine-dependent seizures: always give empirical trial if refractory
• Subtle seizures = most common type in neonates (especially preterm)
• Generalized tonic seizures = worst type, not EEG-confirmed, brainstem release

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CROUP (Acute Laryngotracheobronchitis) - MBBS Exam Notes

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Definition

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Mnemonic: "CROUP" - Key Features

C - Cough (barking, seal-like) R - Rhinorrhea (preceded by URI) O - Obstruction (subglottic - most critical) U - Under 3 years (6 months - 3 years, peak age 1-2 years) P - Parainfluenza virus (type 1 - most common cause, ~80%)

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Epidemiology

• Age: 6 months to 3 years (peak 1-2 years)
• Boys > Girls
• Seasonal: Late autumn and winter (parainfluenza biennial epidemics in odd years)
• Annual incidence: 1.5-6% in children <6 years
• 3-5% of children have at least one episode

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Etiology

Mnemonic: "Para-PIR MI" (PIR = like a pyramid)

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Pathophysiology

Virus → Nasopharynx → spreads to Larynx + Trachea
            ↓
Mucosal edema of SUBGLOTTIS
(only complete cartilaginous ring = most vulnerable)
            ↓
↓ Airway diameter → ↑ airway resistance
(Poiseuille's Law: flow ∝ r⁴)
            ↓
1 mm edema in 18-month-old (subglottic diameter 6.5 mm)
= ~50% reduction in cross-sectional area
            ↓
INSPIRATORY STRIDOR → biphasic stridor → complete obstruction

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Clinical Features

Prodrome (1-2 days)

• Low-grade fever
• Coryza, rhinorrhea
• Upper respiratory symptoms

Classic Triad (Mnemonic: "HBS")

H - Hoarseness B - Barking cough (seal-like, brassy) S - Stridor (initially inspiratory, biphasic in severe)

Additional features

• Symptoms worse at night (classic - anxiety + horizontal position worsen edema)
• Child not toxic-appearing (key differentiator from epiglottitis)
• No drooling (vs. epiglottitis)
• Mean duration: 2-3 days; 80% resolve within 2 days
• Mortality: 1 in 30,000 (rare)

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Severity Assessment: Westley Croup Score

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Radiology

X-ray Neck AP View - "Steeple Sign" (also called "Pencil-tip sign")

• Steeple sign = symmetric subglottic narrowing on AP view, giving the trachea a church-steeple appearance
• Present in only 50% of cases - absent finding does NOT rule out croup
• Not pathognomonic (can be normal variant)
• Lateral view: normal (vs. epiglottitis where lateral shows thumb sign)
• X-ray NOT routinely needed - diagnosis is clinical

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Differential Diagnosis

Mnemonic: "BEaFR" - Big Emergencies after Fever with Respiratory distress

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Treatment

General Principle: Minimize disturbance - anxiety worsens obstruction

Step-by-step Management:

Mild Croup (Westley <4):

• Reassure child and parents
• Keep child with parent (do NOT separate)
• Oral dexamethasone 0.15 mg/kg (single dose)
• Humidified air/mist tent - no evidence of benefit but may be soothing
• Discharge home with advice

Moderate Croup (Westley 4-6):

• Dexamethasone 0.15-0.6 mg/kg PO/IM (max 10 mg) - cornerstone of therapy
• Nebulized budesonide 2 mg (if unable to take oral steroids / vomiting)
• Nebulized L-epinephrine (adrenaline) 1:1000 - 0.5 mL/kg (max 5 mL) via nebulizer
• Observe for rebound (epinephrine effect lasts 1-2 hrs)
• Supplemental oxygen if SpO2 <92%

Severe Croup (Westley >6):

• Oxygen + airway monitoring
• Nebulized epinephrine (may repeat)
• IV/IM dexamethasone
• ICU admission
• Prepare for intubation (use tube 0.5-1 mm smaller than calculated)
• Heliox (helium-oxygen mixture) - reduces turbulent flow

Drug Summary Table

Mnemonic for treatment: "DEB"

D - Dexamethasone (for all but mild) E - Epinephrine nebulized (moderate-severe) B - Budesonide nebulized (if oral steroids not tolerated)

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Mechanism of Corticosteroids in Croup

1. Reduce capillary endothelial permeability → decrease mucosal edema
2. Stabilize lysosomal membranes → decrease inflammatory reaction
3. Topical (budesonide): alpha-mediated local vasoconstriction

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Specific Croup Variants

1. Spasmodic Croup (Recurrent Croup)

• Sudden nocturnal onset without fever
• Child well during day, wakes at night with barking cough + stridor
• No viral prodrome, no fever
• Likely due to allergy/airway hyperreactivity
• Resolves quickly (hours); may recur
• Mist/cold air often helps
• Rule out: subglottic stenosis (congenital/acquired) if recurrent - endoscopy mandatory

2. Membranous Croup (= Bacterial Tracheitis)

• Pseudomembranous tracheitis; S. aureus most common
• Does NOT respond to steroids + epinephrine
• Requires airway management + IV antibiotics

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Indications for Hospital Admission

C - Cyanosis R - Retractions (severe) O - O2 saturation < 92% U - Unable to maintain hydration P - Progressive symptoms despite treatment I - Infant <6 months N - No reliable caretaker / poor social circumstances

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Key Exam Points (High-Yield)

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Summary Mnemonic: "CROUP STAMP"

C - Cold season / Children 6mo-3yr R - Respiratory - barky cough + stridor O - Obstruction at subglottis U - Under parainfluenza virus (type 1) P - Prodrome of URI for 1-2 days

S - Steeple sign on X-ray T - Treatment: Dexamethasone (cornerstone) A - Adrenaline (epinephrine) nebulized for moderate-severe M - Minimize disturbance; no drooling (vs. epiglottitis) P - Prognosis good (mortality 1 in 30,000)

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Croup - As per O.P. Ghai Essential Pediatrics 10th Edition

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Definition

Ghai describes it under "Acute Infections of Upper Respiratory Tract" and "Croup Syndromes" - a group of conditions causing stridor in children.

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Croup Syndromes (Ghai's Classification)

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Etiology

• Parainfluenza virus type 1 - most common (>50%), autumn epidemics
• Parainfluenza types 2 and 3
• RSV - second most common
• Influenza A and B
• Adenovirus, Rhinovirus, Metapneumovirus

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Age and Epidemiology (Ghai Specifics)

• Age: 6 months to 3 years (peak 1-2 years)
• Boys > Girls (2:1)
• Seasonal: late autumn and winter
• Most common cause of stridor in children
• Most common infectious cause of upper airway obstruction in children

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Pathophysiology

Viral infection of nasopharynx
         ↓
Descends to larynx → trachea → bronchi
         ↓
Mucosal inflammation + edema at SUBGLOTTIS
(Subglottis = narrowest part of pediatric airway)
(Only complete cartilaginous ring → cannot expand outward)
         ↓
↓ Airway lumen → turbulent airflow
         ↓
STRIDOR (initially inspiratory → biphasic in severe)

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Clinical Features

Prodrome (1-2 days)

• Low-grade fever
• Coryza, mild cough, running nose

Classic Presentation - Ghai's Triad:

1. Hoarse voice (laryngeal involvement)
2. Barking / brassy cough ("seal bark" - pathognomonic)
3. Inspiratory stridor (± biphasic in severe cases)

Other features:

• Symptoms worse at night
• Child is not toxic (does NOT look sick unlike epiglottitis)
• No drooling
• Low-grade or no fever
• Mild intercostal/subcostal retractions in moderate cases
• Anxiety and agitation worsen symptoms (increased respiratory effort → more turbulence)
• Resolved spontaneously in majority within 48 hours
• Mean duration: 3-7 days total illness

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Severity Classification (Ghai - based on Westley Score)

Westley Croup Score

Clinical Grading (Simpler Ghai version):

• Barking cough
• Mild or no stridor at rest
• No/mild retractions
• Child comfortable, playing

• Stridor at rest
• Moderate retractions (intercostal, subcostal)
• Agitated but arousable
• No cyanosis

• Stridor at rest (biphasic)
• Severe retractions (suprasternal, supraclavicular)
• Cyanosis
• Altered sensorium, fatigue
• Impending respiratory failure

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Investigations

1. X-ray neck AP view - "Steeple sign" (subglottic narrowing; pencil-tip sign)
   • Present in only 50% of cases - absence does NOT rule out croup
   • Not pathognomonic (can be seen in normal children)
2. X-ray lateral neck - Normal in croup (vs. thumb sign in epiglottitis)
3. CBC - usually normal or mild lymphocytosis (viral pattern)
4. Pulse oximetry - continuous monitoring in moderate-severe
5. Nasopharyngeal swab for viral culture - research/epidemiology only

Ghai warning: Do NOT attempt direct laryngoscopy or throat examination in suspected epiglottitis - may precipitate complete obstruction.

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Differential Diagnosis (Ghai Table)

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Management (Ghai Protocol)

General Measures (All cases):

• Minimize handling - crying and agitation worsen obstruction
• Keep child with parent - separation increases anxiety
• Comfortable position (usually upright in parent's lap)
• Humidified air/oxygen - no proven benefit but may be soothing
• Adequate hydration
• Avoid sedation (risk of respiratory depression)
• Avoid throat examination if epiglottitis cannot be excluded

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MILD Croup (Westley ≤2):

• Oral Dexamethasone 0.15 mg/kg (single dose; max 10 mg)
• Reassurance of parents
• Home management with clear return-precaution advice
• Most children do NOT need nebulized epinephrine

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MODERATE Croup (Westley 3-7):

1. Dexamethasone 0.15-0.6 mg/kg PO/IM (max 10 mg) - first-line
   • OR Nebulized Budesonide 2 mg if child vomiting or refusing oral
2. Nebulized Epinephrine (Adrenaline)
   • L-epinephrine (1:1000) - 0.5 mL/kg (max 5 mL) diluted in NS
   • OR Racemic epinephrine 2.25% - 0.05 mL/kg (max 0.5 mL) diluted to 3 mL
   • Onset: 10-30 min; Duration: 1-2 hours (rebound phenomenon)
3. Observe for minimum 3-4 hours after epinephrine
4. Supplemental O2 if SpO2 <92%

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SEVERE Croup (Westley ≥8):

1. Oxygen (blow-by or mask) - monitor SpO2
2. IV/IM Dexamethasone 0.6 mg/kg
3. Nebulized epinephrine - repeat every 20-30 min if needed
4. ICU admission
5. Heliox (70:30 helium:oxygen) - reduces turbulent flow
6. Prepare for intubation if deteriorating
   • Use ETT 0.5-1 mm smaller than predicted (subglottic edema)
   • Have tracheostomy setup ready

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Drug Summary (Ghai Doses):

Ghai key point: Dexamethasone is preferred over prednisolone due to longer half-life (36-72 hours) - a single dose is sufficient. It works by reducing mucosal edema via anti-inflammatory action.

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Rebound Phenomenon (Important Ghai Point)

• Epinephrine effect lasts only 1-2 hours
• Symptoms may rebound after this (return to pre-treatment severity)
• Therefore: observe for 3-4 hours after last dose
• If still symptomatic after observation → admit

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Spasmodic Croup (Recurrent/Midnight Croup) - Ghai Special Section

• Sudden onset at night without fever
• Child well during the day
• No viral prodrome
• Etiology: allergy + airway hyperreactivity (atopic children)
• Self-limiting (resolves within hours)
• May recur on subsequent nights
• Treatment: cool/moist air, reassurance, single dose of dexamethasone
• Important: If recurrent croup → rule out subglottic stenosis by endoscopy

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Indications for Hospital Admission (Ghai)

1. Moderate-severe croup (Westley ≥3)
2. Stridor at rest
3. Significant retractions
4. SpO2 <92%
5. Cyanosis
6. Altered sensorium
7. Age <6 months
8. Poor feeding / dehydration
9. Failure to improve with outpatient treatment
10. Unreliable caretaker or far from medical care

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Complications

1. Respiratory failure (rare)
2. Bacterial superinfection → bacterial tracheitis
3. Otitis media
4. Pneumonia (extension to lower respiratory tract)
5. Pulmonary edema (post-obstructive, after relief of obstruction)

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Prognosis

• Excellent - self-limiting in majority
• 80% resolve within 48 hours
• <1% require intubation
• Mortality: 1 in 30,000 cases
• Recurrent spasmodic croup: outgrown by school age
• Poor prognosis if: bacterial tracheitis, severe HIE, underlying subglottic stenosis

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High-Yield Ghai Exam Points

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Quick Revision Mnemonics (Ghai Context)

F - Foreign body A - Allergy (angioedema, spasmodic croup) C - Croup (LTB, epiglottitis, bacterial tracheitis) E - Extrinsic compression (hemangioma, vascular ring)

Croup: No Drooling, No toxic look, No Dysphagia, Definite Cough Epiglottitis: Drooling, Dysphagia, Dysphonia (muffled), Distressed (toxic)

D - Dexamethasone (all moderate-severe) E - Epinephrine nebulized (moderate-severe) B - Budesonide (if oral steroids refused) O - Oxygen + Observe for rebound