STROKE, COVID-19 INFECTION OR HERPES SIMPLEX ENCEPHALITIS: A DIAGNOSTIC DILEMMA.

Editor,

We present the challenging case of a 71 year-old healthy woman who presented, during the first wave of the Covid-19 pandemic, with a two day history of headaches, fever, confusion and expressive dysphasia. She had no new respiratory complaints. Her background history was not contributory. She was admitted to a Covid-19 isolation unit and a nasopharyngeal swab for viral PCR was sent to test for SARS-CoV-2. Her examination was notable for expressive and receptive dysphasia, vertical gaze nystagmus, right upper limb pronator drift and a positive Babinski’s sign on the right side. She was unable to follow more than one stage commands and exhibited perseverance. There was some fluctuation in her clinical signs initially. She was pyrexial at 37.9 degrees but was otherwise haemodynamically stable.

Initial investigations showed a normal serum WCC and CRP of 19.0. Typical laboratory findings of Covid-19 infection such as lymphopaenia, raised ferritin, deranged liver function tests and raised D-Dimer were absent. An urgent CT brain was completed which showed no acute abnormalities. At this time viral PCR for SARS-CoV-2 returned negative. A lumbar puncture was performed which showed CSF containing WBC 396 per microlitre (differentiation - 87% lymphocytes and 13% polymorphs). The CSF gram stain was negative, glucose was 5.2 mmol/L and protein was 1.12 g/L. Herpes simplex virus 1 was detected on viral PCR. MRI brain showed left temporal and posterior insular oedema with cortical effacement without restriction on diffusion weighted images. (figure).

Figure 1

MRI Brain demonstrating left temporal and posterior insular oedema with cortical effacement without restriction on diffusion weighted imaging.

From the outset we maintained a broad differential. Given the presenting features, stroke, encephalomeningitis and Covid-19 infection were at the forefront of our differential. She was empirically treated with IV acyclovir, ceftriaxone and dexamethasone while awaiting results of lumbar puncture. Following diagnosis she continued on acyclovir alone. This patient gradually recovered with no residual symptoms although she reported retrograde amnesia of her initial presentation. Follow up MRI showed a resolving process.

Discussion

Herpes Simplex virus (HSV) is responsible for 19% of cases of infectious encephalitis.1 It represents significant morbidity and mortality to patients with a one year mortality rate of 14%.2 Typically, patients present with symptoms of fever, headache and confusion although speech disturbance can be seen in 57% and focal neurological deficit in 26% of cases.3 Encephalitis is a known mimic of stroke and atypical presentations can often be misdiagnosed. In some cases this has led to inappropriate treatment with alteplase and in others misdiagnosis can lead to delay in initiating appropriate treatment.4

The emergence of Covid-19 has further confounded this area. Neurological manifestations of Covid-19 can been seen in up to 25% of patients.5 On MRI, unilateral medial temporal lobe oedema, a recognised finding in HSV encephalitis, has been demonstrated in patients with Covid-19 in the absence of HSV.6 This overlap in features risk delay in initiation of correct treatment for patients.

We feel this case is of particular interest as it highlights the importance of maintaining an open mind when managing a patient who has an atypical combination of symptoms particularly in the context of the current pandemic.