Master Rohan, a 3-year-old boy, 2nd order child of non-consanguineous marriage from Varanasi, Uttar Pradesh, presented with complaints of low-to-moderate grade fever for 3 weeks, progressive vomiting and headache for 10 days, excessive irritability followed by drowsiness for 5 days, and one episode of right-sided focal convulsion 2 days prior to presentation.

HOPI

• Fever:
  • Insidious onset, low-to-moderate grade fever for the past 3 weeks.
  • Associated with evening rise of temperature and mild night sweats, partially responsive to paracetamol syrup.
  • No associated chills, rigors, or rash at the onset of fever.
• Headache & Vomiting:
  • The child began complaining of headache 10 days back, initially intermittent, becoming persistent and generalized over the past 5 days.
  • Headache is most severe in early morning hours, associated with excessive crying and head holding.
  • Vomiting started 8 days back, 3–4 episodes per day, projectile in nature, containing undigested food particles, non-bilious, not related to food intake, and effortless without preceding nausea.
• Behavioral Changes & Sensorium:
  • Mother noticed progressive loss of appetite and lethargy over the past 2 weeks.
  • Over the last 5 days, the child became excessively irritable when handled, alternating with daytime drowsiness, reduced spontaneous speech, and decreased recognition of familiar family members.
• Convulsions & Focal Weakness:
  • 2 days prior to admission, the child experienced one episode of abnormal body movement: deviation of the angle of the mouth to the left, tonic stiffening and clonic jerking of the right upper and lower limbs lasting approximately 3–4 minutes, followed by post-ictal sleepiness for 1 hour.
  • Following the seizure, the mother noticed that the child was moving the right upper and lower limbs less spontaneously compared to the left side (right hemiparesis).
• Cranial Nerve Symptoms:
  • Mother noticed inward turning of the right eye (right convergent squint) for the past 3 days.
  • Mild dribbling of saliva from the right angle of the mouth; no nasal regurgitation of liquids or choking during swallowing.

Pertinent Negatives in HOPI:

• No history of prior trauma, fall, or ear discharge (rules out otogenic brain abscess and epidural hematoma).
• No history of loose stools, severe dehydration, or oliguria (rules out sagittal sinus thrombosis and dyselectrolytemia).
• No history of bleeding manifestations, petechial rash, or purpura (rules out meningococcemia and thrombocytopenic hemorrhage).
• No history of loss of attained milestones prior to the onset of the current fever (rules out progressive neurodegenerative storage disorders).
• No history of jaundice, high-colored urine, or pale stools (rules out hepatic encephalopathy and Wilson disease).

Past History

• No history of previous hospital admissions, seizures, or chronic illnesses.
• No history of prior blood transfusions, surgeries, or known drug allergies.
• No history of recent measles or varicella infection in the preceding 6 months.

Family history

• 2nd-order child born to non-consanguineously married parents.
• Tuberculosis Contact History: Paternal grandfather (residing in the same 2-room household) had chronic productive cough with hemoptysis and was diagnosed with sputum-positive pulmonary tuberculosis 4 months ago; he was treated irregularly with anti-tubercular therapy (ATT).
• Older sister (5 years old) is healthy, thriving, and asymptomatic.

Immunization history

• BCG Status: Mother states the child was born at a primary health centre but BCG vaccination was missed due to local vaccine stock-out.
• No BCG scar visible over the left deltoid on examination.
• Received oral polio vaccine (OPV), Pentavalent (DPT-HepB-Hib 1, 2, 3), and MR 1st dose as per the National Immunization Schedule.
• No optional vaccines (PCV, Varicella, Hepatitis A) were administered.

Dietary history

• The child was exclusively breastfed till 6 months of age; complementary feeding with diluted cow's milk and mashed rice was introduced late at 9 months of age.
• Current intake is significantly compromised due to anorexia, illness, and dysphagia over the past 2 weeks.

The expected calories and proteins should be calculated from the ideal body weight, not from current weight.

Socioeconomic and KAP

• Family resides in a semi-pucca, 2-room poorly ventilated house in an urban slum of Varanasi.
• 5 family members live in the household (overcrowding present).
• Paternal grandfather's sputum-positive TB diagnosis was known, but household contact screening and Isoniazid Preventive Therapy (IPT) were not initiated for the children.
• Socioeconomic Status: Lower-middle class according to Modified Kuppuswamy Scale (Score: 8).

Summary of History

General head to toe examination

Pre-Examination Child Behavioral State

• Child State: Child is stuporous, irritable on handling, eyes open intermittently to noxious stimuli, moaning groaning sounds, localized withdrawal to painful stimuli.
• Pediatric Glasgow Coma Scale (pGCS): E3 V3 M4 = 10/15.

Vitals

• Heart Rate: 84 bpm (relative bradycardia for fever, indicating raised intracranial pressure).
• Respiratory Rate: 24/min, regular, no chest retractions.
• Blood Pressure: 108/68 mmHg (>95th percentile for age/height, reflecting Cushing's hemodynamic response).
• Temperature: 38.2°C (100.8°F) axillary.
• Capillary Refill Time: <2 seconds, peripheral pulses well felt.

Anthropometry

Head-to-Toe Markers

• Head & Fontanelle: Anterior fontanelle closed. Macewen's sign ("cracked pot sound") is positive on skull percussion over the frontoparietal junction (indicating dilated ventricles / hydrocephalus).
• BCG Scar: Absent over left deltoid.
• Skin & Hair: Dry, lack-lustre hair with easy pluckability; no erythema nodosum, tuberculides, or petechiae.
• Eyes: No phlyctenular conjunctivitis. Dilated fundoscopic examination reveals:
  • Bilateral early papilledema (blurring of nasal disc margins, hyperemic disc, loss of venous pulsations).
  • No choroid tubercles identified on direct visualization.
• Lymph Nodes: Multiple discrete, non-tender, non-matted, mobile cervical lymph nodes palpable bilaterally, largest ~1 × 1 cm in the right anterior cervical chain.
• Spine: Normal alignment; no gibbus deformity, tenderness, or cold abscess.

Systemic Examination

CNS Examination

1. Higher Mental Functions & Meningeal Signs

• Level of Consciousness: Drowsy/stuporous (GCS 10/15).
• Meningeal Irritation Signs:
  • Neck Rigidity: Markedly positive (marked resistance to passive neck flexion).
  • Kernig's Sign: Positive bilaterally at 120° extension.
  • Brudzinski's Neck Sign: Positive (reflex flexion of both hips and knees on passive neck flexion).

2. Cranial Nerves

• CN II (Optic): Pupils 3 mm bilaterally, sluggishly reactive to direct and consensual light. Fundus shows bilateral early papilledema.
• CN III, IV, VI: Right eye displays resting inward deviation (esotropia); failure of right eye abduction on horizontal gaze tracking (Right CN VI palsy). Normal vertical gaze and pupillary size.
• CN V (Trigeminal): Corneal reflex present bilaterally. Motor jaw clenching preserved.
• CN VII (Facial): Right-sided Upper Motor Neuron (UMN) facial palsy — flattening of right nasolabial fold, deviation of angle of mouth to left upon crying/grimacing, with preserved forehead wrinkling bilaterally.
• CN VIII: Blinks and turns sluggishly to loud auditory stimuli.
• CN IX, X: Gag reflex present; palate elevates symmetrically; no pooling of secretions in the pharynx.
• CN XI: Symmetrical shoulder movement on noxious stimulation.
• CN XII: Tongue midline in oral cavity; no fasciculations.

3. Motor System Examination

4. Sensory & Cerebellar Examination

• Sensory: Withdraws to painful stimuli in all four limbs (delayed and sluggish in right extremities).
• Cerebellar: Cannot be formally evaluated due to altered sensorium and hemiparesis.
• Involuntary Movements: No choreoathetosis, tremors, or dystonic posturing at rest.

other systems

• Respiratory System: Bilateral symmetrical chest expansion. Vesicular breath sounds heard bilaterally with occasional scattered fine inspiratory crepitations in the right infrascapular region.
• Cardiovascular System: S1, S2 heard normally; no murmurs, rubs, or gallop.
• Abdomen: Soft, non-tender; liver palpable 2 cm below right costal margin (soft, smooth, non-tender span 7 cm); spleen not palpable. No ascites or shifting dullness.

Summary

Differential Diagnosis

Investigation Protocol & Diagnostic Workup

flowchart TD
    A["Suspected Pediatric TBM"] --> B["1. Urgent Non-Contrast CT / Contrast MRI Brain"]
    B --> C{"Check for Mass Effect / Brainstem Herniation"}
    C -->|No contraindication| D["2. Lumbar Puncture & CSF Analysis"]
    C -->|Severe midline shift / impending herniation| E["Start Empirical ATT + Dexamethasone + Anti-edema therapy; Defer LP"]
    D --> F["CSF Microscopy, Biochemistry, TB-PCR / Xpert MTB/RIF Ultra"]
    A --> G["3. Source & Dissemination Search: Chest X-ray, Gastric Aspirate, Tuberculin Skin Test"]
    A --> H["4. Baseline Organ Profiles: LFT, RFT, Serum Electrolytes (Na+ for SIADH/CSW)"]

1. Cerebrospinal Fluid (CSF) Analysis

• Pressure: Markedly elevated (>200–300 mm H₂O).
• Cytology: Moderately elevated leukocyte count (typically 50–500 cells/µL) with marked lymphocytic predominance (>80%) (neutrophils may appear transiently in early stage 1).
• Biochemistry:
  • CSF Protein: Markedly elevated (100–500 mg/dL, and up to >1000 mg/dL in cases with spinal block / Froin's syndrome).
  • CSF Glucose: Markedly decreased (<40 mg/dL, with a CSF-to-Blood Glucose Ratio < 0.5, frequently <0.3).
  • Cobweb / Pellicle Formation: Classic cobweb clot forming upon standing the CSF tube overnight at 4°C (due to high fibrinogen content).
• Microbiological Confirmation:
  • Ziehl-Neelsen / Auramine-Rhodamine Staining: Centrifuged thick smear examination for Acid-Fast Bacilli (AFB).
  • CBNAAT / GeneXpert MTB/RIF Ultra on CSF: High sensitivity and specificity; provides rapid detection of Mycobacterium tuberculosis and Rifampicin resistance within 2 hours.
  • CSF Mycobacterial Culture (MGIT 960): Gold standard for definitive identification and full drug susceptibility testing (DST).

2. Neuroimaging (Contrast-Enhanced MRI / CT Brain)

• Classic TBM Triad on MRI:
  1. Basal Meningeal Enhancement: Dense exudates in the interpeduncular cistern, Sylvian fissures, and suprasellar cisterns.
  2. Hydrocephalus: Symmetrical dilatation of lateral and third ventricles (communicating hydrocephalus due to basal exudates blocking arachnoid villi; or non-communicating due to aqueductal compression by tuberculoma/ependymitis).
  3. Tubercular Vasculitic Infarctions: Ischemic infarctions characteristically involving the "Tubercular Zone" (basal ganglia, internal capsule, thalamus, and head of caudate nucleus) due to endarteritis of middle cerebral and lenticulostriate perforators.
• Tuberculomas: Ring-enhancing or nodular granulomas with central caseation and surrounding edema.

3. Diagnostic Workup for Primary Focus & Dissemination

• Tuberculin Skin Test (Mantoux): 2 TU PPD intradermally; induration $\ge 10\text{ mm}$ (or $\ge 5\text{ mm}$ in SAM/HIV) read at 48–72 hours is positive. (Note: May be falsely negative in up to 30–50% of advanced TBM due to anergy).
• Chest Radiograph: Anteroposterior view to identify primary complex, mediastinal lymphadenopathy, miliary mottling, or cavitary disease.
• Gastric Aspirate / Induced Sputum for CBNAAT: 3 consecutive morning fasting gastric aspirates for AFB smear and GeneXpert.
• Lymph Node FNAC: If peripheral lymphadenopathy is present, fine needle aspiration for cytology, AFB stain, and CBNAAT.

4. Baseline Monitoring Investigations

• Liver Function Tests (LFT): Baseline SGOT, SGPT, Total/Direct Bilirubin, and Alkaline Phosphatase prior to starting hepatotoxic ATT (Isoniazid, Rifampicin, Pyrazinamide).
• Serum Electrolytes (Na⁺, K⁺): Essential to monitor for hyponatremia secondary to Syndrome of Inappropriate ADH Secretion (SIADH) or Cerebral Salt Wasting (CSW).
• Renal Function Tests & Complete Hemogram: Baseline BUN, Serum Creatinine, Hb, TLC, DLC, ESR.
• HIV Serology: Mandatory in all cases of childhood tuberculosis.

Management Plan

flowchart LR
    A["TBM Treatment Triad"] --> B["1. Anti-Tubercular Therapy (ATT)"]
    A --> C["2. Corticosteroids (Dexamethasone)"]
    A --> D["3. Management of Raised ICP & Hydrocephalus"]

1. Anti-Tubercular Therapy (NTEP 2024 Pediatric Guidelines)

• Regimen: 2 months of 4-drug HRZE followed by 10 months of 3-drug HRE (Total duration: 12 months):
  • Intensive Phase (2 Months):
    • Isoniazid (H): $10\text{ mg/kg/day}$ (Max: $300\text{ mg/day}$)
    • Rifampicin (R): $15\text{ mg/kg/day}$ (Max: $600\text{ mg/day}$)
    • Pyrazinamide (Z): $35\text{ mg/kg/day}$ (Max: $1500\text{ mg/day}$)
    • Ethambutol (E): $20\text{ mg/kg/day}$ (Max: $1000\text{ mg/day}$)
  • Continuation Phase (10 Months):
    • Isoniazid (H): $10\text{ mg/kg/day}$
    • Rifampicin (R): $15\text{ mg/kg/day}$
    • Ethambutol (E): $20\text{ mg/kg/day}$
• Pyridoxine (Vitamin B6) Supplementation: $10\text{–}20\text{ mg/day}$ orally to prevent Isoniazid-induced peripheral neuropathy (especially in SAM).

2. Adjuvant Corticosteroid Therapy

• Indication: Mandatory in all cases of TBM (Stages 1, 2, and 3) to reduce basal exudates, cerebral edema, vasculitis, and incidence of stroke and hydrocephalus.
• Drug & Dosage:
  • Intravenous Dexamethasone: $0.4\text{ mg/kg/day}$ (or Oral Prednisolone $2\text{–}4\text{ mg/kg/day}$) for 4 weeks.
  • Tapering Schedule: Taper gradually over the next 2 to 4 weeks based on clinical and radiological recovery (Total steroid course: 6–8 weeks).

3. Management of Raised ICP & Hydrocephalus

• Head End Elevation: Nurse the child with head elevated at 30° in the midline to facilitate cerebral venous drainage.
• Medical Management of Cerebral Edema:
  • Intravenous 20% Mannitol: $0.5\text{–}1.0\text{ g/kg/dose}$ IV infusion over 20–30 minutes every 6–8 hours for acute ICP spikes (with serum osmolality monitoring).
  • Hypertonic Saline (3% NaCl): $3\text{–}5\text{ mL/kg}$ IV bolus for impending herniation.
  • Oral Acetazolamide: $20\text{–}40\text{ mg/kg/day}$ in 3 divided doses $\pm$ Oral Furosemide $1\text{ mg/kg/day}$ for communicating, non-progressive hydrocephalus.
• Surgical Management of Hydrocephalus:
  • Ventriculoperitoneal (VP) Shunt: Indicated for progressive hydrocephalus, non-communicating hydrocephalus, or failure of medical therapy.
  • Endoscopic Third Ventriculostomy (ETV): Considered in selected non-communicating hydrocephalus cases without dense basal scarring.

4. Management of Comorbidities & Complications

• Seizure Control:
  • Acute control: IV Midazolam $0.1\text{ mg/kg}$ or IV Lorazepam $0.1\text{ mg/kg}$.
  • Maintenance: IV/Oral Levetiracetam ($20\text{–}40\text{ mg/kg/day}$) or Sodium Valproate ($20\text{–}30\text{ mg/kg/day}$).
• Electrolyte Management (SIADH vs CSW):
  • SIADH: Euvolemic/Hypervolemic hyponatremia $\rightarrow$ Fluid restriction ($60\text{–}70\%$ maintenance).
  • Cerebral Salt Wasting (CSW): Hypovolemic hyponatremia with severe natriuresis $\rightarrow$ Vigorous volume replacement with normal saline $\pm$ Fludrocortisone.

5. Nutritional Rehabilitation & Supportive Care

• Nasogastric Tube Feeding: High-calorie, high-protein feeds (F-75 transitioning to F-100 per WHO SAM protocol).
• Nursing Care for Bedridden Child:
  • Two-hourly position changes to prevent decubitus ulcers.
  • Methylcellulose eye drops and eye padding for lagophthalmos in facial palsy / comatose state.
  • Gentle passive range-of-motion physiotherapy to all four limbs to prevent fixed contractures.
• Long-term Follow-up & Rehabilitation:
  • Brainstem Auditory Evoked Response (BERA) at completion of therapy to screen for sensorineural hearing loss.
  • Visual acuity, visual evoked potentials (VEP), and serial neurodevelopmental assessment.