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High-grade glioma mimicking acute viral encephalitis − three case reports
  1. J H Rees,
  2. R S Howard
  1. National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK


    The clinical features of viral encephalitis consist of headache, fever, seizures and encephalopathy. We report three patients with high-grade gliomas presenting with encephalitic illnesses. The diagnosis of brain tumour should always be borne in mind if definite evidence for a viral infection is not obtained.

    • glioma
    • viral encephalitis
    • encephalopathy

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    Viral encephalitis is characterised by headache, confusion, altered consciousness with or without seizures, and fever. The most commonly identified cause of sporadic community-acquired encephalitis is herpes simplex virus (HSV) type I, which may be diagnosed on viral culture of cerebrospinal fluid (CSF), polymerase chain reaction (PCR) analysis looking for HSV DNA, serological testing for IgM antibodies, or brain biopsy. Characteristically the virus attacks the medial temporal lobes and insular cortex giving rise to a focal encephalitis which carries a significant mortality rate.1 Rarely, the patient presents with symptoms and signs of raised intracranial pressure, giving rise to the possibility of a temporal lobe abscess. The converse situation, whereby a high-grade tumour presents as an acute encephalitic illness, has only rarely been reported. The following three cases illustrate that this diagnosis should always be borne in mind if definite evidence for a viral infection causing the encephalopathy is not obtained, especially if the PCR test is negative for the presence of viral DNA.

    Case reports

    Case 1

    A 41-year-old woman presented with tonic– clonic seizures, fever, drowsiness and confusion. Magnetic resonance imaging (MRI) showed extensive high signal abnormality in the left temporal lobe and posterior parietal region (figure 1). CSF was normal. A presumptive diagnosis of herpes simplex encephalitis (HSE) was made and she improved after intravenous acyclovir. However, her seizures persisted and 2 years later her MRI scan showed an increase in the size of the temporal lesion (figure 1). Approximately one month later, she was found unconscious at home. A CT scan now showed a large lesion with considerable midline shift. Emergency decompression was unsuccessful and she died without regaining consciousness. The histology of the lesion was glioblastoma multiforme.

    Figure 1

    Coronal T2-weighted MRI scans showing an area of high signal in the left medial temporal lobe which was identical to the images on presentation 2 years earlier. Two years later and one month before the patient's death, the abnormality is more extensive and involves the inferior parietal lobe

    Case 2

    A 49-year-old man became acutely confused and then had serial tonic-clonic seizures. On admission he was pyrexial, tachycardic and unconscious. MRI showed extensive high T2 signal change affecting the right temporal and frontal lobes with some mass effect (figure 2). CSF examination including PCR for HSV DNA was negative. He was started on acyclovir and gradually improved. He had persistent simple partial seizures and a repeat MRI 3 weeks later showed no change. A stereotactic brain biopsy was carried out and revealed an anaplastic astrocytoma. He was treated with external beam radiotherapy followed by combination chemotherapy.

    Figure 2

    Axial T2-weighted MRI scan showing diffuse high signal change in the right anterior temporal lobe with a second smaller focus more posteriorly

    Case 3

    A 72-year-old woman presented with a 2-week history of episodes of vagueness and confusion. MRI revealed a lesion involving the grey and white matter of the left temporal lobe but also a similar process involving the right temporal lobe and uncus (figure 3). There was some mass effect and mild contrast enhancement. It was felt that the appearances were more consistent with HSE than glioma. A CSF sample taken 5 days after starting acyclovir was normal, including PCR for HSV DNA. She remained persistently confused with frequent simple and complex partial seizures. One month later MR guided stereotactic biopsy of the left temporal lobe revealed a high-grade astrocytoma which was not treated at the request of her family.

    Figure 3

    Axial T2-weighted MRI scan showing extensive left medial temporal high signal with some abnormality also seen medially in the right temporal lobe


    All three patients described above presented acutely with confusion and seizures. Fever was present in the first two cases and all patients had extensive areas of high signal on T2-weighted MR imaging within one or both (Case 3) temporal lobes. HSE was therefore diagnosed on both clinical and radiological grounds. Results of CSF examination were normal in each case, but as this was not incompatible with HSE, the patients were treated with a full course of intravenous acyclovir. No patient received steroids at presentation and the improvement in patients 1 and 2 presumably occurred as a consequence of achieving seizure control. It was only when the results of the PCR came back as negative that the initial diagnosis was reconsidered. In cases 2 and 3 a high-grade temporal lobe glioma was diagnosed using CT or MR-guided stereotactic biopsy within one to two months of the original presentation. The first patient, however, remained undiagnosed for over 2 years and biopsy was not carried out principally because the MRI scan appearances of the lesion had not obviously changed. Her final MRI scan showed that the tumour had increased in size but the decision to biopsy electively was never made as she presented soon after in extremis. Presumably the tumour had undergone transformation from low-grade to high-grade in a short space of time.

    The distinction between acute viral encephalitis and a glioma is usually easily made on clinical and radiological grounds. PCR can be used to identify viral DNA in the CSF and allows early diagnosis of HSE.2 Occasionally the presentation is atypical and HSE may mimic a rapidly expanding temporal lobe mass, giving rise to considerable diagnostic difficulty.3-5 However, the converse situation whereby a malignant glioma presents as an acute encephalopathy is much rarer.

    This ‘encephalitic’ presentation of temporal lobe tumours has been previously alluded to in a study of 432 patients who underwent brain biopsy for presumed HSE, in the pre-MRI era.6 Five out of 95 (6%) patients who were biopsy-negative for HSE had tumours, two metastatic colonic adenocarcinomas, one primary CNS lymphoma and two glioblastomas. In another study looking at the differential diagnosis and outcome of 65 patients presenting with an acute encephalopathy over a 17-year period, only one patient out of 34 in whom a definite or probable diagnosis could be made had a tumour. This was a 45-year-old man presenting with a short history of headache and confusion who had a right temporal lobe lesion. Three years later a biopsy revealed an oligodendroglioma.7

    Learning points

    • a malignant brain tumour can present acutely as fever and encephalopathy with bilateral abnormalities on MRI scanning

    • stereotactic biopsy should be considered in patients with temporal lobe mass lesions if no definitive diagnosis is made after the results of PCR analysis for common viruses are available

    This very low frequency suggests that a primary CNS tumour rarely presents as an encephalitic illness. With the advent of PCR analysis brain biopsy is seldom undertaken to diagnose HSE, particularly as the most common differential diagnoses include other viral encephalitides for which no specific treatment is currently available. However, we believe that stereotactic biopsy should be considered in all patients with temporal lobe mass lesions if no definitive diagnosis is made after the results of PCR analysis for common viruses are available. This is because the procedure carries very little risk and other potentially treatable conditions such as bacterial abscesses, fungal infections and tuberculosis would otherwise be missed.