What is the investigation of choice for enterovirus-induced polyradiculoneuropathy?

Investigation of Choice for Enterovirus-Induced Polyradiculoneuropathy

For enterovirus-induced polyradiculoneuropathy (acute flaccid myelitis/paralysis), the investigation of choice is RT-PCR testing of respiratory specimens (nasopharyngeal aspirate or throat swab), combined with stool samples and CSF, with respiratory specimens being particularly critical since certain enterovirus types (especially EV-D68) are rarely detected in CSF or stool. 1

Primary Diagnostic Approach

Sample Collection Priority

Multiple specimens from different anatomical sites should be collected simultaneously as soon as possible after symptom onset: 1

• Respiratory specimens (nasopharyngeal aspirate, nasopharyngeal swab, or throat swab) - These are mandatory for all cases with CNS/paralysis/myelitis involvement 1
• Stool samples - Should be obtained in all suspected cases 1
• CSF - Should be tested but may be negative even in confirmed cases 1
• Blood samples - Should be collected before any blood products (especially intravenous immunoglobulin) are administered 1

Critical Rationale for Respiratory Specimens

Respiratory specimens must always be collected from all acute flaccid myelitis cases because EV-D68, a common cause of enterovirus-associated polyradiculoneuropathy, has only rarely been detected in CSF or stool samples. 1 This represents a critical diagnostic pitfall - relying solely on CSF testing will miss many cases. 1

Viral loads are typically higher in stool, blood, and respiratory samples than in CSF, making these peripheral specimens more sensitive for detection. 1

Diagnostic Testing Method

RT-PCR as Gold Standard

Reverse transcriptase PCR (RT-PCR) assays targeting the 5′non-coding region (5′NCR) should be used for diagnosis due to superior sensitivity, specificity, and short turnaround time compared to viral culture. 1, 2

RT-PCR has been shown to be far more sensitive than cell culture for detection of enteroviruses in clinical samples. 1 Research studies demonstrate that RT-PCR detects enterovirus in 97% of culture-positive CSF samples and identifies an additional 66% of cases with negative cultures. 3

Methods to Avoid

• Virus isolation should NOT be used for routine diagnosis but can be reserved for further characterization at the national level 1
• Serological methods (ELISA, neutralization tests) should NOT be used for diagnosis of acute enterovirus infection 1

Timing and Sample Handling Considerations

CSF Timing Sensitivity

CSF PCR sensitivity decreases significantly when collected >2 days after clinical onset. 4 In one study, CSF PCR was positive in 76% of enteroviral meningitis cases overall, but sensitivity was lower for specimens obtained >2 days after symptom onset. 4

Stool Sample Advantages

Stool PCR remains highly sensitive even 5-16 days after clinical onset, with 96% positivity in confirmed cases and 92% positivity in late-collected samples. 4 This makes stool specimens particularly valuable when patients present later in their disease course. 4

Sample Preparation Requirements

For stool samples, proper preparation is critical: 1

• Disaggregate in buffer (e.g., saline) 1
• Clarify by centrifugation to avoid PCR inhibition 1
• Include an internal control to identify inhibitory compounds 1

Clinical Interpretation Caveats

Prolonged Viral Shedding

Enteroviruses colonize the throat and gut for weeks to months, so detection in these sites must be interpreted cautiously and does not automatically demonstrate causation. 1 However, in the context of acute neurological symptoms consistent with polyradiculoneuropathy, positive results support the diagnosis. 1

Special Populations

In immunocompromised patients (especially those on IgG-depleting therapies like rituximab), the threshold for investigation should be low, and viral shedding in stool can persist for years. 1

Recommended Testing Algorithm

1. Collect all three specimen types immediately: respiratory (nasopharyngeal aspirate/swab), stool, and CSF 1
2. Collect blood sample before any immunoglobulin administration 1
3. Perform RT-PCR targeting 5′NCR on all specimens 1, 2
4. If initial testing is negative but clinical suspicion remains high, repeat stool and respiratory testing as these remain positive longer than CSF 1, 4
5. Consider classical polio testing if acute flaccid paralysis without myelitis features 1