A Case of Maternal Herpes Simplex Virus Encephalitis During Late Pregnancy
Investigations: A pregnant 25-year-old woman at 32 weeks' gestation was admitted to an emergency unit after her husband had found her drowsy and with her tongue bitten. The day before admission, the patient had developed a fever of 39 °C, was suffering from headaches, was nauseated and had vomited. On admission, she had anterograde and retrograde amnesia, but no somatic neurological deficits were detected.
Diagnosis: Routine laboratory testing, lumbar puncture, cerebrospinal fluid analysis, routine bacteriology, brain MRI, and polymerase chain reaction testing for neurotropic viruses including herpes simplex virus types 1 and 2.
Maternal herpes simplex virus type 1 encephalitis.
The Case Details: Antiviral and anticonvulsive therapy, supportive treatment, and cesarean section.
A pregnant 25-year-old woman at 32 weeks' gestation was admitted to an emergency unit after her husband had found her drowsy and with her tongue bitten. The patient had anterograde and retrograde amnesia suggestive of a postictal state, indicating that she had experienced a first-ever generalized seizure. For the previous 3 days, she had been experiencing frontotemporal headaches associated with phonophobia and photophobia.
On the day before admission, the patient had developed a fever of 39 °C, was nauseated and had vomited. On admission, no somatic neurological deficits were detected. There were no signs of eclampsia as a possible underlying cause of the seizures–the patient's blood pressure was normal and proteinuria was absent. The patient had no history of genital lesions or their symptoms.
Figure 1. (click image to zoom) Brain MRI scans of a patient with acute herpes simplex type 1 encephalitis. (A) On admission, coronal FLAIR imaging showed T2 hyperintensities within the right temporopolar and temporomesial region (arrow). (B) Corresponding diffusion restriction was seen on axial diffusion-weighted sequences (arrow). (C,D) Repeat imaging was performed after the patient had experienced two further epileptic seizures and was somnolent. The right temporal lobe lesion was seen to have increased in size on the FLAIR sequences (C; arrow), and there was corresponding increased diffusion restriction, with the diffusion abnormalities now also involving the cortex (D; arrow). The repeat FLAIR images suggested that another lesion had appeared in the medial aspect of the left temporal lobe (C; arrowhead). No diffusion restriction was detected for this possible new lesion (D). Abbreviation: FLAIR, fluid-attenuated inversion recovery.
Laboratory examination of the patient's blood revealed leukocytosis (15.6 x 109 white blood cells/l; normal range 3.5-10.5 x 109 white blood cells/l) due to increased neutrophils (13.95 x 109 cells/l; normal range 1.6-7.4 x 109 cells/l), and raised levels of C-reactive protein (17 mg/l; normal value < 5 mg/l).
Lumbar puncture was performed and cerebro-spinal fluid (CSF) analysis revealed a pleocytosis with predominantly mononuclear cells (99%) of 125 cells/ul and 10 erythrocytes/ul, a normal protein level (0.37 g/l; normal value < 0.42 g/l) and a slightly increased lactate level (2.3 mmol/l; normal value < 2.1 mmol/l). A brain MRI scan with coronal fluid-attenuated inversion recovery (FLAIR) sequences revealed a temporopolar and mesial hyperintensity on the right side of the patient's brain (Figure 1A). On diffusion-weighted MRI sequences, the lesion showed areas of diffusion restriction (Figure 1B).
Herpes simplex virus encephalitis (HSE) was suspected on the basis of the patient's medical history, clinical presentation, and CSF and MRI findings, and antiviral therapy with intravenous aciclovir (12.5 mg/kg every 8 h) was started, together with anticonvulsive prophylaxis consisting of four doses of 1 mg intravenous lorazepam administered at 6 h intervals. In addition, betamethasone (two doses of 12 mg given intramuscularly 24 h apart) was administered to stimulate lung maturation in the fetus. Polymerase chain reaction (PCR) testing of the patient's CSF was positive for herpes simplex virus type 1 (HSV-1) and negative for herpes simplex virus type 2 (HSV-2), confirming a diagnosis of HSV-1 encephalitis. Serology was negative for HSV-1 IgG, indicating that the patient had a primary herpes virus infection.
On the third day of hospitalization, the patient experienced a second generalized seizure, along with increasing drowsiness and meningeal signs, which prompted the instigation of intravenous anticonvulsive therapy with 100 mg lamotrigine once daily; this regimen was supplemented with 2.5 mg levetiracetam once daily after the patient had a third seizure on the fifth day of hospitali-zation. A second MRI scan at this point showed that the right-sided herpetic lesion had increased in volume and that signs of another lesion had appeared in the medial aspect of the left temporal lobe (Figure 1C). No diffusion restriction was detected for this possible new lesion (Figure 1D).
The deterioration of the patient's clinical status and the progression of the HSV-1 lesions in her brain led to concerns for the safety of the fetus, and a cesarean section was, therefore, performed under general anesthesia. No complications were experienced during the procedure, and a preterm but otherwise healthy infant (2,340 g birth weight) was delivered. The newborn was immediately started on aciclovir prophylaxis and was transferred to the neonatal intensive care unit. No viral copies were detected on HSV-1 PCR of the amniotic fluid, umbilical cord blood or venous blood of the infant drawn at delivery, and consequently its aciclovir prophylaxis was discontinued.
The mother experienced no further seizures and her aciclovir therapy was stopped 21 days after its initiation when her PCR results from a second CSF examination were negative for HSV-1. Other findings were a 98% mononuclear pleocytosis of 40 cells/ul, a protein level of 0.51 g/l and a lactate level of 1.4 mmol/l. No neurological or neuro-psychological deficits were present in the mother or her newborn infant at discharge 4 weeks after initial hospitalization. The mother did not experience any further seizures, but anticonvulsive prophylaxis with lamotrigine was continued until the first follow-up 6 months after discharge.
1. Which of the following viruses is the most common cause of sporadic encephalitis in the United States?
2. Which of the following symptoms is not among the triad that forms the clinical hallmark of acute viral encephalitis?
- Influenza A virus
- Herpes simplex virus (HSV)
3. Which of the following is the most common cause of neonatal herpes infection?
- Altered mental state
4. Which of the following tests is most likely to be recommended for the diagnosis of encephalitis during pregnancy?
- Herpes zoster
- None of the above
5. Which of the following tests is the modality of choice for diagnosing HSV CNS disease in adults?
- Magnetic resonance imaging (MRI)
- Computed tomography (CT)
- Electroencephalography (EEG)
- Brain biopsy
- HSV serum antibodies
- Polymerase chain reaction (PCR) testing of CSF
- CSF cytology
Answers & Explanations:
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