How to manage a child with elevated ALK PHOS, low creatinine, and suspected chronic encephalitis?

Management of Elevated Alkaline Phosphatase in a Child with Suspected Chronic Encephalitis

The elevated alkaline phosphatase (456) in this 10-year-old is likely physiologic bone growth-related and should not distract from the critical priority: establishing a definitive diagnosis for the suspected chronic encephalitis through comprehensive metabolic workup, autoimmune testing, and neuroimaging, as the encephalitis itself poses far greater risks to morbidity and mortality than the laboratory abnormalities. 1

Immediate Diagnostic Priorities for the Encephalitis

Metabolic Evaluation

• Obtain comprehensive metabolic investigations including renal, liver, bone & thyroid profiles, arterial blood gas analysis, plasma and CSF lactate, ammonia, pyruvate, amino acids, very long-chain fatty acids, and urinary organic acids, as metabolic encephalopathies can present with chronic neurological deterioration 1
• The low creatinine (0.30) combined with elevated BUN (40) suggests either poor muscle mass from chronic illness or a pre-renal state requiring assessment 1

Autoimmune/Inflammatory Workup

• Perform extensive autoimmune testing including FBC, ESR, CRP, ANA, ENA, dsDNA, ANCA, C3, C4, lupus anticoagulant, cardiolipin, thyroglobulin, thyroperoxidase antibodies, ferritin, fibrinogen, and triglycerides 1
• Test for voltage-gated potassium channel complex and NMDA receptor antibodies, as antibody-mediated encephalitis has poorer outcomes if untreated and can present with chronic/subacute courses 1
• Consider serum and CSF ACE, serum 25OH Vitamin D, and 24-hour urinary calcium to evaluate for sarcoidosis or other granulomatous diseases 1

Neuroimaging

• MRI brain is the imaging modality of choice and should be obtained urgently, as it detects cerebral changes in approximately 90% of encephalitis cases versus only 25% sensitivity for CT 2
• MRI with gadolinium can identify brainstem changes and basal meningeal enhancement suggestive of chronic infections (tuberculosis, brucellosis, Lyme) or malignancy 1

Addressing the Alkaline Phosphatase Elevation

Physiologic Consideration

• Alkaline phosphatase of 456 in a 10-year-old female is likely within normal range for age, as children have markedly elevated alkaline phosphatase during growth spurts (normal pediatric ranges can exceed 500 U/L) 1
• Obtain bone-specific alkaline phosphatase isoenzymes or liver function tests (GGT, ALT, AST) to differentiate bone from hepatic sources if there is clinical concern 1

When to Investigate Further

• If liver enzymes are elevated or there are clinical signs of hepatobiliary disease, consider abdominal ultrasound 1
• The normal CBC and remainder of CMP argue against significant hepatic pathology 1

Infectious Workup for Chronic Encephalitis

CSF Analysis (if not already performed)

• Lumbar puncture is essential unless contraindicated by raised intracranial pressure or coagulopathy 1
• Send CSF for PCR testing of HSV-1, HSV-2, VZV, enteroviruses, EBV, CMV, HHV6, and HHV7 1
• Include CSF for tuberculosis (PCR, culture, AFB), fungal studies (cryptococcal antigen, culture), and oligoclonal bands 1
• Obtain paired serum and CSF for antibody testing against common viral pathogens 1

Special Considerations for Chronic Presentation

• Immunocompromised patients and those with subacute presentations require broader testing including toxoplasma, cryptococcus, and consideration of progressive multifocal leukoencephalopathy (JC virus) 1
• Measles can cause subacute sclerosing panencephalitis (SSPE) years after primary infection in immunologically normal children 1

Management of Renal Parameters

Addressing the BUN/Creatinine Discrepancy

• The BUN of 40 with creatinine of 0.30 yields a BUN/creatinine ratio >100, suggesting pre-renal azotemia or poor nutritional status 1
• Ensure adequate hydration and nutritional support, as chronic encephalitis patients may have poor oral intake 2, 3
• Monitor fluid balance and electrolytes closely, particularly if considering contrast imaging studies 1

Multidisciplinary Approach

Specialist Involvement

• Obtain neurological specialist consultation within 24 hours for patients with suspected encephalitis to optimize outcomes 2
• Consider infectious disease consultation for guidance on chronic CNS infections 2
• Involve intensive care if there is any decline in consciousness level for airway protection and management of increased intracranial pressure 2, 3

Biopsy Consideration

• Brain and meningeal biopsy should be considered if initial comprehensive workup is non-diagnostic and the patient continues to deteriorate, as this can identify rare infections, autoimmune processes, or malignancy 1

Critical Pitfalls to Avoid

• Do not attribute the encephalitis to the laboratory abnormalities (elevated alk phos, low creatinine) without thorough investigation, as these are likely secondary findings 1
• Do not delay CSF examination if clinically safe to perform, as this is the single most important diagnostic test 1
• Do not overlook autoimmune causes, which now represent a significant proportion (21%) of encephalitis cases and require immunotherapy rather than antimicrobials 4
• Do not discharge without definitive or suspected diagnosis and comprehensive rehabilitation planning, as sequelae may not be immediately apparent 2