When the Tests Fail A Rare Case of HSV1 Encephalitis with Negative CSF PCR

Introduction

Herpes Simplex Virus 1 (HSV-1) encephalitis is a life-threatening condition typically confirmed through cerebrospinal fluid (CSF) analysis using polymerase chain reaction (PCR). But what happens when the gold-standard test yields a false negative? A recent case study sheds light on this medical anomaly, emphasizing the crucial need for clinical vigilance and repeat testing in suspicious cases.
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A Closer Look at the Case

A 76-year-old male presented with altered mental status, fever, and headache. Despite a clinical picture suggestive of HSV-1 encephalitis, initial PCR testing of the cerebrospinal fluid was negative. Here’s how the diagnosis eventually unfolded:

• Initial presentation: Fever, disorientation, and neurological symptoms.
• Imaging results: CT scans were unremarkable; however, MRI revealed abnormal signals in the temporal lobetypical of HSV encephalitis.
• First CSF PCR test: Returned negative despite strong clinical suspicion.
• Repeat testing: A second lumbar puncture confirmed HSV-1 via positive PCR.

This case emphasizes the importance of clinical judgment even when lab results are inconclusive.
Read the full study at https://doi.org/10.36959/810/004

Clinical Implications and Broader Context

False negatives in HSV-1 PCR testing, though rare, can lead to delayed diagnosis and treatment, potentially increasing morbidity and mortality. Medical professionals should consider:

• Initiating empirical antiviral therapy in suspicious cases.
• Repeating PCR tests if the initial one is negative but clinical signs persist.
• Relying on neuroimaging and clinical judgment alongside laboratory tests.

The Centers for Disease Control and Prevention (CDC) underscores the importance of early diagnosis and prompt treatment for viral encephalitis, especially HSV-related cases.

A detailed analysis can be found in our main journal article, offering full insights into the diagnostic challenges and clinical reasoning.

Best Practices for Diagnosing HSV-1 Encephaliti

To enhance diagnostic accuracy, clinicians should:

• Maintain high suspicion despite negative initial tests.
• Use MRI findings to support diagnosis.
• Repeat CSF PCR within 48–72 hours if clinically indicated.
• Start acyclovir therapy immediately upon suspicion.

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