An Update on Diagnostic Imaging Studies for Viral Encephalitis

Table 1.  Neuroimaging features of viral encephalitis or encephalopathy.

	HSV	VZV	HIV	JEV	JCV	Influenza virus
MRI: abnormal findings by conventional MRI sequences	Abnormal intensity in limbic cortices, frontal and temporal lobes (hyperintense on FLAIR and T2-W, hypointense on T1-W)	Abnormal intensities according to leukoencephalopathy, vasculopathy and ventriculitis (in particular at cortical–white matter junction)	Regional atrophy in gray matter (particularly in the basal ganglia) and in white matter Ventricular expansion Vasculitis or vasulopathy	Abnormal intensity in thalamus, basal ganglia, cerebellum, brain stem and cerebral cortex (hyperintense on T2-W, hypointense on T1-W)	Abnormal intensity in white matter typically occurs in the parieto-occipital lobes and corpus callosum (hyperintense on FLAIR and T2-W, hypointense on T1-W)	Abnormal intensity in any lesions (sometimes reversible) Focal hemispheric edema Vasculitis or vasculopathy Acute necrotizing encephalopathy (mostly in childhood)
MRI: DWI	Acute stage: hyperintense on DWI and hypointense on ADC in same lesion	Stroke due to vasculitis or vasculopathy (small, deep, subcortical ischemic stroke)	Stroke due to vasculitis or vasculopathy (large, cortical hemispheric stroke)	Variable appearance on DWI in acute and subacute stage Increase in ADC in subacute stage	Active lesion: consists of central core (hypointense on DWI, hyperintense on ADC) and peripheral rim (hyperintense on DWI)	Reversible lesion in the splenium of the corpus callosum (hyperintense on DWI and hypointense on ADC; in mild case of IAEE)
	Subacute stage: decrease of hyperintensity on DWI and increase on ADC				Advancing lesion: not homogenous (intermediate to low on ADC)
SPECT	Increase in uptake of 99mTc-HMPAO, decrease in uptake of 99mTc-ECD at the acute phase	Hyperintensity at the acute phase, normointensity at the recovery phase	Hyperintensity with thallium-201 at the acute phase	Hyperintensity, especially bilateral thalamic, at the acute phase Hypointensity at the subacute phase

99mTc-ECD: Technetium-99m-ethyl cysteinate dimer; 99mTc-HMPAO: Technetium-99m-labeled hexamethylpropyleneamine oxime; ADC: Apparent diffusion coefficient; DWI: Diffusion-weighted image; FLAIR: Fluid-attenuated inversion recovery; IAEE: Influenza virus-associated encephalitis/encephalopathy; JCV: John Cunningham virus; JEV: Japanese encephalitis virus; T1-W: T1-weighted image; T2-W: T2-weighted image; VZV: Varicella zoster virus.

Authors and Disclosures

Naoki Kawamura¹, Madoka Kizawa¹, Akihiro Ueda¹, Yoshiki Niimi¹ & Tatsuro Mutoh<sup>*1

1</sup>Department of Neurology, Fujita Health University School of Medicine, Aichi, Japan.

Financial & competing interests disclosure
Part of the manuscript was funded by the grant-in-aid from the Ministry of Culture, Education, Sports and Science of Japan (No. MEXT S1001034). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

*Author for correspondence
Tel.: +81 562 93 9295 n Fax: +81 562 93 1856 tmutoh@fujita-hu.a.cjp

Sidebar

Executive Summary

Encephalitis Caused by Herpes Simplex Encephalitis

• Herpes simplex encephalitis (HSE) is the most common virus-associated severe encephalitis, involving brain lesions in areas such as the limbic portion of the temporal lobe as well as the frontal lobe.

• Pathologically, necrotic, inflammatory or hemorrhagic lesions of the brain parenchyma are observed.

• Previous reports on neuroimaging findings suggested the superiority of MRI over CT scanning, especially in the early course of the disease.

MRI

• Conventional magnetic resonance sequences:

  • Conventional magnetic resonance sequences in routine practice include T1-weighted image (T1-W), T2-weighted image (T2-W) and fluid-attenuated inversion recovery pulse image (FLAIR).

  • FLAIR imaging is more sensitive than T2-W image in the detection of the lesions at the acute phase of the illness.

  • FLAIR and T2-W imaging can detect the lesions of viral infection within the first 48 h.

• Diffusion-weighted imaging

  • Diffusion-weighted image (DWI) sequence was originally used for the detection of acute lesions of brain infarction, allowing the differentiation of fresh lesions from old infarction.

  • MRI appearance on DWI is closely related to the pathologic changes caused by viral invasion such as congestion, lymphocytic perivascular cuffing and thrombus formation in the acute phase of the illness.

  • These changes result in the occurrence of cytotoxic edema, leading to the restricted diffusion and low apparent diffusion coefficient.

  • DWI sequence of these regions shows hyperintensity areas.

  • In the subacute phase, apparent diffusion coefficient starts to increase. At this stage, vasogenic and/or interstitial collection of fluid occurs leading to the hyperintense area on T2-W image.

  • Cytotoxic edema suggest the fulminant necrotizing varient of the disease, whereas vasogenic edema suggest mild pathological changes and a better prognosis.

SPECT

• HSE patients show increased uptake of 99mTc-HMPAO tracer in lesions caused by HSV.

• The degree of uptake of radioactivity correlates to the prognosis of the patients.

• If different tracers are used, the results might differ from those obtained using another tracer in HSE patients.

HIV Encephalitis/Encephalopathy

• In HIV encephalitis/encephalopathy, infected monocytes activate microglia, leading to diffuse white-matter injury and neurodegeneration.

• HIV encephalitis/encephalopathy usually result in cognitive impairment and involuntary movement.

• MRI findings in these cases include loss of parenchyma leading to an increase in cerebrospinal fluid volume, decrease in striatal gray matter volume and decreases in cerebral white-matter volume.

• These progressive striatal and white-matter volume losses are already recognized even in the medically asymptomatic stage of the disease.

• HIV vasculopathy or vasculitis might be the principal cause of stroke in these patients.

• HIV vasculopathy seems to be associated with large, cortical, hemispheric stroke, while VZV vasculitis appears to be present more often with deep-seated, small, subcortical ischemic infarcts.

Japanese Encephalitis Virus

• Japanese encephalitis virus has an affinity with the thalami of the brain.

• Japanese encephalitis virus invades the CNS by way of the hematogenous route, and subsequent spreading occurs along the dendritic axons not only to the thalami, but also to the basal ganglia, brain stem, cerebellum and cortical areas of the brain.

• MRI findings in typical cases show bilateral thalamic involvement on both T2-W and FLAIR sequences. Typical lesions show hyperintensity on both T2-W and FLAIR images, and hypointensity on T1-W images.

JC virus

• JC virus is responsible for the development of progressive multifocal leukoencephalopathy.

• Typical findings on MRI show hypointensity on T1-W and hyperintensity on T2-W imaging compared with normal white matter.

• Some cases show lesions on the parieto-occipital white matter and the corpus callosum.

Influenza Virus

• Influenza virus can cause encephalitis in rare cases.

• MRI examination using a DWI sequence reveals hyperintense lesions in the splenium of the corpus callosum.

• The presence of hyperintense lesions in the splenium of the corpus callosum appears to be a useful indicator for a good prognosis.

Varicella Zoster Virus

• Varicella zoster virus can cause aseptic meningitis, leukoencephalopathy, vasculopathy, dorsal root or cranial nerve ganglionitis, polyradiculoneuritis, ventriculitis, necrotizing angitis and meningoencephalitis.

• MRI findings include abnormal signal intensity and swelling of the cerebral cortex, basal ganglia, cortical–white matter junction or cerebellum.

Dengue Virus

• Dengue virus is an RNA virus, and four different serological subtypes exist, type 2 and 3 usually cause encephalitis.

• Brain lesions on MRI show hyperintensity on T2-W and FLAIR imaging, and hypointensity on T1-W imaging.