TRAINEE CORNER

https://doi.org/10.5005/jp-journals-10089-0024
Journal of Acute Care
Volume 1 | Issue 2 | Year 2022

Acute Viral Encephalitis in Adults

Sarath Kumar¹ https://orcid.org/0000-0001-6075-8495, Shiv Kumar², Darshan U Siddappa³

^1,3Department of Critical Care Medicine, Manipal Hospitals, Bengaluru, Karnataka, India

²Department of Critical Care Medicine, Narayana, Bengaluru, Karnataka, India

Corresponding Author: Sarath Kumar, Department of Critical Care Medicine, Manipal Hospitals, Bengaluru, Karnataka, India, Phone: +91 9148535357, e-mail: saratmbbs@gmail.com

Received on: 13 September 2022; Accepted on: 26 September 2022; Published on: 31 December 2022

ABSTRACT

Encephalitis is a syndrome characterized by altered mental status along with acute fever, seizures, and neurological deficits. The syndrome has many causes, the most commonly identified causes are neurotropic viruses. Herpes simplex virus (HSV) encephalitis is a potentially life-threatening condition which can be diagnosed with a combination of history, examination, magnetic resonance imaging (MRI) brain, and lumbar puncture. We report a case of a young immunocompetent adult presented with fever, altered mentation, and seizure. We are reporting classical findings of HSV encephalitis in an MRI brain study. We also described a few common viral encephalitis encountered in clinical practice.

How to cite this article: Kumar S, Kumar S, Siddappa DU. Acute Viral Encephalitis in Adults. J Acute Care 2022;1(2):112-117.

Source of support: Nil

Conflict of interest: None

Keywords: Encephalitis, Herpes simplex virus, Magnetic resonance imaging.

INTRODUCTION

Encephalitis is a syndrome characterized by altered mental status along with acute fever, seizures, and neurological deficits.¹ The syndrome has many causes, the most commonly identified causes are neurotropic viruses. HSV 1 and 2 account for 10–20% of all viral encephalitis cases.² Cerebrospinal fluid (CSF) analysis with HSV polymerase chain reaction (PCR) is the gold standard for diagnosis, however, false-negative PCR assay can be seen in patients with low viral load in the initial phases of illness.³ MRI can be used as an adjunct in diagnosis in cases with negative PCR assay and high clinical suspicion or in patients whose lumbar puncture could not be performed. We described a young patient who presented with fever and altered sensorium and was diagnosed with HSV encephalitis and characteristic MRI findings and subsequent discussion on common encephalitis syndromes in the form of a tutorial.

CASE DESCRIPTION

We report a case of a 24-year-old male patient who was in good health 3 days prior to admission to our hospital when he developed acute onset fever and headache followed by an episode of seizure with subsequent loss of consciousness and altered sensorium. The past medical history was insignificant.

On admission, the patient was febrile and in the postictal phase with the Glasgow Coma Scale (GCS) of E3V4M5 with no focal neurological deficits. Initial laboratory evaluation for the metabolic cause of altered sensorium was not contributory. He was started on empirical antimicrobials with suspicion of meningoencephalitis, and other supportive measures after sending appropriate cultures.

Magnetic resonance imaging brain with contrast was done which revealed some tell-tale features. Bilateral asymmetric medial temporal lobe fluid-attenuated inversion recovery (FLAIR) hyperintensities (right > left) involving hippocampus and amygdala (Figs 1 to 3) and FLAIR hyperintensities in the insular cortex, perisylvian cortex bilateral, basifrontal lobes, and inferolateral external capsule along with edema of these areas (Fig. 4). Diffusion-weighted sequences showed diffusion restriction in the cortex of the above-mentioned regions (Figs 5) and apparent diffusion coefficient (ADC) showed T2 shine through (Fig. 6). There is evidence of intracerebral hemorrhage (Fig. 7). There was no involvement of basal ganglia and cingulate gyri.

Fig. 1: Coronal T2: hyperintensity in the medial temporal lobe—hippocampus, amygdala, and adjacent insular cortex

Fig. 2: Axial T2 FLAIR-basifrontal lobe adjacent to median temporal lobe hyperintense lesions

Fig. 3: Axial T2 FLAIR-bilateral (right > left) medial temporal lobe, hippocampus, parahippocampus, and amygdala

Fig. 4: Axial FLAIR-insular cortex hyperintense lesion

Figs 5A to D: (A) Axial FLAIR-insular cortex hyperintense lesion; (B) Diffusion-weighted image (DWI)—axial-restriction in cortex-right medial temporal lobe; (C) DWI—axial-restriction in cortex-right medial temporal lobe; (D) DWI—axial-restriction in cortex-right medial temporal lobe

Fig. 6: Axial ADC-T2 shine through (to differentiate vasogenic edema—from cytotoxic edema-infarct)

Fig. 7: Susceptibility weighted images (SWI)—axial—no hemorrhage

Lumbar puncture revealed a lymphocytic predominant picture with elevated protein levels. The CSF PCR encephalitis panel was reported to be positive for HSV 1.

The antiviral acyclovir 15 mg/kg every 8 hours that was initiated was continued along with other supportive measures. Gradually there was an improvement in his neurological status with no neurological deficits, there were no further episodes of seizures, and he was discharged home after 5 days.

Early and accurate diagnosis by MRI and CSF findings and prompt treatment with acyclovir helped in early and complete recovery.

How do you differentiate meningitis from encephalitis?

Meningitis is the inflammation of the subarachnoid space, which is the space between the arachnoid and pia mater. Encephalitis is defined as the inflammation of brain parenchyma (Table 1).¹
Can you describe the differences between viral and postinfectious encephalitis?

It is difficult to distinguish between viral and postinfectious encephalitis based on clinical presentation alone as both clinical conditions can present with focal neurological deficits and altered mental status. However, CSF analysis in postinfectious encephalitis is lymphocytic predominant with no evidence of direct central nervous system (CNS) infection. MRI brain is pathognomonic, which shows diffuse, multifocal, and asymmetrical lesions on T2- and FLAIR-weighted sequences.¹³
What are the common viral pathogens leading to viral encephalitis?

The causative organism for viral encephalitis depends on geographical location. In India, the most common cause is Japanese encephalitis virus followed by dengue virus, West Nile virus, chikungunya virus, herpes viruses, and enteroviruses.¹⁴
What are the signs and symptoms the patients with viral encephalitis present with? (Table 2)
Describe and discuss the imaging modalities highlighting the specific diagnostic features of various etiologies of viral encephalitis (Table 3).
What are the MRI findings of HSV encephalitis?
- Hyperintensities involving the cortical and the subcortical regions of bilateral temporal, frontal lobes, and insula on T2-weighted images.⁴
- Restricted diffusion, gyral swelling, loss of gray-white matter interface, and mild enhancement can be seen.
- Petechial hemorrhages are usually seen after 48 hours.
What is the sensitivity of MRI in diagnosing HSV encephalitis?

The sensitivity and specificity of MRI in diagnosing HSV encephalitis are 80% and >95%, respectively.¹⁵
Do we need to perform computed tomography (CT)/MRI before lumbar puncture in all patients with features suggestive of encephalitis?

**Table 1:** Features of meningitis, encephalitis, and meningoencephalitis
	Meningitis	Encephalitis	Meningoencephalitis
Causes	Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis	Herpes simplex virus (HSV), varicella-zoster virus (VZV), enterovirus	HSV, VZV, listeria
Systemic signs and symptoms (fever, endocytosis)	Present	Present	Present
Meningeal signs	Present	Not seen	Present
Mental status changes	Sometimes	Hallmark feature	Incidence more than in meningitis
Seizures	Uncommon	Often
Focal neurological deficits	50% of patients—usually late in the course	Hallmark feature	More often than meningitis

**Table 2:** Clinical features of viral encephalitis¹
Altered level of consciousness	Dysphasia
Agitation	Seizures
Inattentiveness	Cranial neuropathies
Drowsiness	Focal deficits in limbs
Comatose	Movement disorders
Impaired cognition	Meningism
Confusion	Photophobia
Disorientation	Neck stiffness
Amnesia	Headache
Behavioral change

**Table 3:** MRI findings in common encephalitis in India
Type	Site	MRI findings
Herpes simplex virus 1⁴	Frontal and temporal lobes. Rarely extratemporal	T2 hyperintensity, diffusion restriction, sometimes hemorrhage
Herpes simplex virus 2⁴	Diffuse brain involvement	T2 hyperintensity, diffusion restriction, sometimes hemorrhage
Japanese encephalitis⁵^,⁶	Thalami is commonly involved. Basal ganglia, pons, midbrain, cerebellum are involved	T2 hyperintensity, restricted diffusion, sometimes hemorrhage (Fig. 11)
Dengue encephalitis⁷^,⁸	Bilateral thalami, pons, medulla	Hyperintensity on T2 images with areas of restricted diffusion, sometimes petechial hemorrhages and diffuse cerebral edema are seen (Fig. 10)
COVID-19 encephalitis³^,⁹^,¹⁰	Mesial temporal lobe, white matter lesions	Unilateral FLAIR and/or diffusion hyperintensities in the mesial temporal lobe (Fig. 9) followed by non-confluent, multifocal white matter hyperintensities, variable white matter microhemorrhages (Fig. 8)
HIV encephalitis¹¹^,¹²	Periventricular and deep white matter	Diffuse cerebral atrophy, T2 hyperintensities in periventricular, deep white matter

Figs 8A and B: (A) Diffusion-weighted image (DWI) of the brain showed high signal intensity at the site of splenium of corpus callosum; (B) ADC map extracted from DWI demonstrated a slight decrease in ADC value on the same lesion

Figs 9A to D: Axial FLAIR in four different COVID-19 patients (A) FLAIR hyperintensities located in the left medial temporal lobe; (B) FLAIR ovoid hyperintense lesion located in the central part of splenium of corpus collosum; (C) Extensive and confluent supratentorial white matter FLAIR hyperintensities; (D) Hyperintense lesions involving both middle cerebellar peduncles

Figs 10A to F: Axial FLAIR images show bilateral symmetrical hyperintensities in thalami, pons, bilateral temporal lobe and cerebellum (A and B). GRE image show loss of signal in bilateral thalamus (C). DWI and ADC images shows restriction on diffusion in bilateral thalamus (D and E). Post contrast image show peripheral enhancement in bilateral thalami (F)

Figs 11A and B: (A) MRI, T2 FLAIR (fluid-attenuated inversion recovery) depicting symmetrical hyperintense signals in bilateral thalamus and basal ganglia; (B) T2 FLAIR image demonstrated hyperintense signal changes in midbrain

A CT scan or MRI of the head is frequently ordered by clinicians prior to performing a lumbar puncture to rule out an intracranial abnormality which can cause a herniation.

Infectious Diseases Society of America¹⁶ recommends imaging before lumbar puncture in the following conditions:

History of central nervous system disease (mass lesion and stroke).
New-onset seizure.
Papilledema.
Altered level of consciousness.
Focal neurological deficit.

Despite guidelines, many clinicians tend to perform imaging before lumbar puncture which leads to delays in diagnosis and institution of treatment. Swedish guidelines modified earlier recommendations and removed altered mental status from the list of indications to perform imaging before lumbar puncture, this practice has led to earlier treatment and better outcomes.¹⁷

Is MRI along with clinical features like GCS helpful in prognostications?

Evidence for prognostication of viral encephalitis with MRI or GCS is available only for herpes encephalitis. Prognostication may be difficult in the initial stages where the diagnosis is uncertain or viral encephalitis is due to other viral encephalitis like HIV, influenza, etc. Low GCS, seizures, and focal neurological deficits in the initial period are poor prognostic indicators for HSV encephalitis in a 5-year prospective study by Feng et al.¹⁸ MRI is mainly helpful for diagnosis during the initial period of treatment and evaluation. There is no data to guide prognostication with MRI in non-HSV encephalitis. In HSV encephalitis, extensive MRI changes and thalamic diffusion signal changes were associated with poor outcomes. Clinical improvement like improvement of GCS and reduction in seizures may suggest a good prognosis and may not need radiological prognostications. Extensive brain involvement with diffuse cerebral edema and a comatose patient is a definitive poor prognostic indicator.¹⁹
Is sparing of basal ganglia still believed to be pathognomic of herpes simplex encephalitis (HSE)?

Basal ganglia and thalami are typically spared in HSE. HSE involves the medial temporal lobes, insular cortex, and cingulate gyrus. The presence of lesions in these areas should raise suspicion of middle cerebral artery occlusion due to thrombus and will help to rule out HSE.
What are the EEG features in encephalitis?

There is no specific EEG feature seen only in viral encephalitis. In HSE, the EEG changes may be localized to the temporal lobes. EEG in HSE can show periodic discharges unilaterally or bilaterally. There may be three-phase waves which may be seen in any encephalopathy. Bilateral slow triphasic waves may be seen in West Nile encephalitis.²⁰
How do CSF examination, serology, PCR, and brain biopsy contribute to the diagnosis of encephalitis?

Cerebrospinal fluid in viral encephalitis will show normal glucose and increased protein levels, with normal or mildly increased pressure. The cell count is a mononuclear type which is elevated (10–500 cells/mm³). PCR of CSF can be used for the diagnosis of HSV, cytomegalovirus (CMV), Epstein–Barr virus (EBV), varicella-zoster virus (VZV), dengue, etc. PCR may be highly sensitive in HSV for diagnosis. If the initial PCR is negative but HSV is strongly suspected clinically, PCR may be repeated after 3–7 days. Serology may be useful for the diagnosis of viral encephalitis like HIV, EBV, and CMV.

Brain biopsy is the last resort for diagnosis in suspected viral encephalitis when there is rapid clinical deterioration despite treatment and all other diagnostic modality is noncontributory. Brain biopsy can be considered postmortem or antemortem—electively or during a decompressive craniectomy for brain edema. The biopsy may show microglial nodules on histopathological examination.
What is the differential diagnosis of viral encephalitis?

Acute disseminated encephalomyelitis, systemic infections—tropical illness (e.g., rickettsia disease and malaria), nonviral encephalitis like tuberculosis, toxoplasmosis, etc., any systemic cause for encephalopathy can be a differential diagnosis—uremia, sepsis. Autoimmune disease with CNS vasculitis, autoimmune encephalitis, and paraneoplastic syndromes.
What is the empirical treatment? How do you reduce CSF pressure in these cases?

Empirical treatment with acyclovir 10 mg/kg should be started in all suspected cases of viral encephalitis pending CSF results. Empirical treatment with antibiotics (ceftriaxone 2 gm 12 hourly) should also be added before CSF results. Empirical doxycycline can be added if clinical suspicion of rickettsia illness.¹ Reduction of CSF pressure in case of cerebral edema can be done using osmotherapy with 3% saline or mannitol. Therapeutic external ventricular drainage of CSF drainage may be considered in case of hydrocephalus. Other neuroprotective measures include euglycemia, normocarbia, and head-end elevation.
What are the prognostic determinants of viral encephalitis?

The prognosis will depend on the cause of viral encephalitis. Data are sparse for non-HSV viral encephalitis. Early administration of acyclovir, higher GCS at presentation, and younger age were good prognostic determinants in HSE. The mortality due to viral encephalitis has reduced to about 5–20% with treatment. About 50–60% of cases who recover from intensive care have long-term cognitive and neurological sequelae.¹

CONCLUSION

Magnetic resonance imaging is an important step in the approach to patients with suspected viral encephalitis and MRI patterns specific for a few diseases. Knowledge about various patterns helps in early appropriate diagnosis and management.

ORCID

Sarath Kumar https://orcid.org/0000-0001-6075-8495

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