Bilateral independent periodic lateralised epileptiform discharges at presentation followed by rapid recovery: novel observations from a case of Epstein-Barr virus encephalitis

Abstract

Bilateral independent periodic lateralised epileptiform discharges (BIPLEDs) in electroencephalograms (EEGs) are commonly caused by anoxic encephalopathy and central nervous system infections. They are associated with coma and high mortality and are thus markers of poor prognosis. We present a case of encephalitis who presented with BIPLEDs in EEG. Though the clinical, EEG and MRI features closely resembled herpes simplex encephalitis, further investigations proved it to be Epstein-Barr virus (EBV) encephalitis. Despite the presence of BIPLEDs in the EEG, the patient had a rapid clinical response to therapy with acyclovir. We emphasise that BIPLEDs may not always indicate poor prognosis especially in the setting of EBV encephalitis.

Background

Bilateral independent periodic lateralised epileptiform discharges (BIPLEDs) in electroencephalograms (EEGs) represent independent and asynchronous occurrence of periodic lateralised epileptiform discharges (PLEDs) in bilateral cerebral hemispheres.¹ Anoxic encephalopathy and central nervous system infections are the most common causes of BIPLEDs.² Compared with PLEDs, BIPLEDs are more commonly associated with coma and high mortality. Mortality in BIPLEDs is around 50%–60% in various studies.^{2 3} We illustrate this previously unreported presentation of Epstein-Barr virus (EBV) encephalitis in an adult with BIPLEDs in EEG and highlight the positive prognosis of BIPLEDs observed in our case.

Case presentation

A 30-year-old man was admitted with altered mental status and focal seizures around 10 days following a short febrile illness. He was drowsy at presentation with no meningeal signs or focal neurologic deficits. MRI study of the brain showed T2 and fluid-attenuated inversion recovery hyperintensities involving temporal, medial frontal and insular regions (figure 1A,B). Video-EEG monitoring on the first day showed diffuse slowing of the background activity with BIPLEDs over the temporal regions consisting of sharp waves occurring at 1–2 s intervals (figure 2A). Isolated right (figure 3A) and left (figure 3B) temporal PLEDs were also seen. He was initiated on parenteral antiseizure drugs and acyclovir. Cerebrospinal fluid (CSF) obtained by lumbar puncture revealed a mild lymphocytic pleocytosis, normal sugar and 0.60 g/L protein. The CSF IgG index was normal at 0.3. PCR study of CSF for herpes simplex virus done elsewhere in the first week of illness and repeated on the second day of admission was negative. It was also negative for a host of viruses including cytomegalovirus and enteroviruses. However, CSF was positive for EBV by PCR analysis.

Figure 1.

MRI study of the brain showing T2 and fluid-attenuated inversion recovery hyperintensities involving bilateral medial frontal and insular regions (A) and bilateral temporal regions (B).

Figure 2.

Video-electroencephalogram on the first day showing diffuse slowing of the background activity with bilateral independent periodic lateralised epileptiform discharges over the temporal regions consisting of sharp waves occurring at 1–2 s intervals.

Figure 3.

Video-electroencephalogram (EEG) on the first day showing isolated right (A) and left (B) temporal periodic lateralised epileptiform discharges. EEG after 5 days showing bilateral temporal slow waves (C,D).

Outcome and follow-up

The patient had no further seizures and showed good clinical improvement. Repeat Video-EEG done after 5 days showed return of background activity. There were bilateral temporal slow waves and few right and left temporal sharp waves (figure 3C,D). Acyclovir was given for 14 days. He made a total clinical recovery. Neuropsychological assessment revealed normal intelligence and anterograde amnesia. Video-EEG at this juncture revealed disappearance of BIPLEDs, intermittent slow waves with normal background activity and good reactivity. Repeat CSF PCR study was negative for EBV.

Discussion

The closest differential for the clinical presentation of herpes simplex encephalitis (HSE) seems to be EBV encephalitis. However, in contrast to HSE, there still seems to be no definitive data on the diagnosis and treatment of EBV encephalitis. This is probably due to the following reasons:

1. It usually affects the central nervous system as a coinfection.⁴ Being lymphotropic, it can remain dormant in CSF lymphocytes and appear later as part of an inflammatory response to other infections and hence a positive PCR may not confirm active infection.⁵

2. Available literature on EBV encephalitis is mostly in the paediatric population where multifocal grey and white matter abnormalities in the MRI have been reported but very little information is available about the EEG findings. Adult EBV infection may be having different MRI and EEG findings.

In addition to HSE, BIPLEDs have been documented in encephalitis due to Haemophilus influenzae, Klebsiella and Mycoplasma pneumoniae.⁶ Ours is the first reported instance of EBV encephalitis presenting with BIPLEDs in EEG. The presence of PLEDs in EEG in EBV encephalitis has been reported in a teen and an adult, which resolved on recovery from the illness.^{7 8} This clinical, EEG and MRI picture closely mimics HSE and requires a high degree of suspicion for proper diagnosis. The absence of other viral agents in the CSF along with the negativisation of EBV DNA after 2 weeks of acyclovir therapy in our case strongly suggests EBV encephalitis.

Benign chronic BIPLEDs in EEG have been described in association with bilateral hippocampal infarction.⁹ Our patient may be an example of a relatively benign BIPLEDs occurring in association with an acute encephalitic illness. Similar benign nature of BIPLEDs has also been observed with HIV encephalopathy.¹⁰ Serial EEGs in our patient showed rapid decrease and disappearance of BIPLEDs within 2 weeks of illness. This could be due to the early and prompt treatment with acyclovir. Our case illustrates the novel observation of BIPLEDs at presentation in EBV encephalitis. Also, the presence of BIPLEDs at presentation need not always indicate a bad prognosis.

Learning points.

• Epstein-Barr virus (EBV) encephalitis must be considered in the differential diagnosis of herpes simplex encephalitis considering the similarities in the clinical, electroencephalogram and MRI features.

• Bilateral independent periodic lateralised epileptiform discharges (BIPLEDs) in electroencephalogram (EEG) may be seen at presentation of EBV encephalitis.

• The treatment of EBV encephalitis is not established, and our case would suggest the beneficial effects of acyclovir in this situation.

• The presence of BIPLEDs need not indicate poor prognosis in the setting of EBV encephalitis.