Other Infections of the Brain

CHAPTER 42 Other Infections of the Brain


HIV Encephalitis

HIV encephalitis (HIVE) is direct infection of the brain with the human immunodeficiency virus (HIV). Alternate names include HIV-associated dementia (HAD) and HIV encephalopathy.

Clinical Presentation

HIV infection may lead to motor and cognitive deficits. The motor symptoms are usually mild and may manifest as a slowing of repetitive movements or difficulty with balance. Disabling HIV dementia presents as a slow decline in a patient’s cognitive abilities with a characteristic triad of cognitive, behavioral, and motor dysfunctions.2 Nearly 50% of HIV patients in the United States demonstrate neuropsychological testing performance that is below expectations compared to matched normative groups. HIV-associated neurocognitive disorders (HAND) can be subclassified into asymptomatic neurocognitive impairment (ANI), mild cognitive disorder (MND), and HIV-associated dementia (HAD).


HIV enters the central nervous system (CNS) early in the course of infection, possibly by using a cloak of human proteins to sneak into the cells (Trojan horse “stealth entry”).3 The brain then serves as an important reservoir for autonomous, selfsustaining, and persistent infection. Within the brain the virus resides primarily within microglia and macrophages.4


Two neuropathologic consequences of cerebral HIV infection are multinucleated giant cell encephalitis (MGCE) and progressive diffuse leukoencephalopathy (PDL).5 MGCE and PDL may be two ends of a broad spectrum of morphologic changes induced by HIV. MGCE is characterized by perivascular accumulation of inflammatory cells, predominantly microglia cells, monohistiocytes, and macrophages. In PDL, diffuse loss of myelin and axons with reactive astrocytosis and distinctive multinucleated giant cells are seen in the deep white matter.5 New variants of HIVE have been reported recently, including severe leukoencephalopathy with intense perivascular macrophage and lymphocyte infiltration and chronic “burnt out” forms of HIVE.

The highest concentrations of HIV are found in the basal ganglia (especially the globus pallidus), subcortical regions, and frontal cortices.



MRI has documented reduction of gray matter volume in the basal ganglia and posterior cortex and generalized loss of volume in the white matter.9

White matter lesions are found in about 80% of HAD patients (range: 43%-100%) and usually assume any of four patterns: diffuse, patchy, focal, and punctiate.10 These lesions are usually isointense or minimally hypointense on T1-weighted (T1W) imaging, have high signal on T2-weighted (T2W) imaging, and show no mass effect or enhancement (see Fig. 42-1). Two distinct patterns are observed on T2W imaging: (1) diffuse bilateral symmetrical high signal intensity in the white matter appears to represent HIV encephalopathy (see Fig. 42-1) and (2) patchy bilateral lesions with high T2 signal intensity in the gray and white matter appear to represent HIV encephalitis.10 High signal intensity lesions may also be seen in the splenium of the corpus callosum and in the crura of the fornices.11 Long-term studies show progressive increase in the white matter lesions with disease progression.1214 Fluid-attenuated inversion recovery (FLAIR) sequences are superior to T2W images for detection of white matter lesions, especially in periventricular and subcortical locations.15 1H MR spectroscopy (MRS) is being used increasingly to detect early CNS involvement by HIV. Decreased N-acetyl-aspartate (NAA) and elevated choline (Cho) and myoinositol (MI) levels (lower NAA/creatine [Cr] ratio, increased Cho/Cr ratio, increased MI/Cr ratio) in the basal ganglia or frontal white matter are seen in early HIV infection of the brain.16 In HAD patients, perfusion MRI shows a statistically significant decrease in regional cerebral blood flow (rCBF) in the inferior lateral frontal cortices bilaterally with an increase in rCBF in the posteroinferior parietal white matter bilaterally.17

MRI and MRS have now been used in the clinical management of patients with HAD who are receiving potent antiretroviral therapy.1820 A combination of antiretroviral drugs in patients with HAD may result in stabilization or even regression of white matter signal intensity abnormalities observed on MR images.19,20 The progression of white matter lesions on initial follow-up studies is likely the result of postinflammatory reactions due to immune reconstitutive effects after the initiation of highly active antiretroviral therapy (HAART).20,21 Despite potent therapies, the neuronal damage appears to progress without clinical manifestations and the progression of cerebral atrophy is apparent on MR images.20

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a subacute opportunistic infection caused by the JC polyomavirus (JCV, hence the name JCV infection).


The JC virus was isolated in 1971 and named for the first patient in whom this virus was isolated.22 Approximately 5% (0.7%-11%) of HIV patients will develop PML during the course of their illness.23,24 PML may also occur in immunosuppressed patients with malignant diseases. Two cases of PML have been described recently in patients with multiple sclerosis who were treated with the α4-integrin inhibitor natalizumab.25


Demyelinated areas are recognized as discolorations of the white matter.

The histopathologic hallmark of PML is demyelination with enlarged oligodendroglial nuclei and bizarre astrocytes.27 The central portion of the lesion is characterized by an almost total breakdown of the myelin sheath and by axonal damage, with an increase in the extracellular space; the most medial area of lesion development consists of oligodendrocytes with nuclear inclusions and partially destroyed myelin, with a relative sparing of axons.

PML is usually multifocal, and the lesions may occur in any location in the white matter, thalamus, brain stem, and cerebellum. In rare cases, PML may be limited to the posterior fossa.28



On T2W MR images, PML lesions are patchy, scalloped, high signal intensity white matter lesions with extension along the white fibers (Fig. 42-3).24,28 Subcortical arcuate fibers are involved, mass effect is mild or absent, and peripheral, faint enhancement is a rare feature.2931 On T1W images, the PML lesions are markedly hypointense.24,28 Magnetization transfer ratios (MTRs) can be used to differentiate between PML and lesions in HAD. The mean MTR value of PML lesions is significantly lower than that of HAD lesions (26.1% vs. 47.9%).32 On DWI, different signal behavior between the lesion center and the extending margin has been observed (Fig. 42-4).33 On apparent diffusion coefficient (ADC) maps, signal intensity was elevated in the central area, whereas at the lesion margins two areas were distinguished: (1) a newer portion, with reduced water diffusibility compatible with cytotoxic edema and (2) less recent portions with intermediate values.33

The 1H spectra of PML lesions are characterized by significantly reduced NAA, lactate presence, and increased choline and lipids.34,35 A decrease in NAA is the result of axonal loss, and the presence of lactate is related to cellular hypoxia. The increase in choline and lipid may reflect an accumulation of myelin breakdown products.

Although at present there is no specific therapy for PML, recent studies have shown clinical and radiologic improvement in patients with PML who underwent HAART.3638 In patients with prolonged survival regression or stabilization, MRI findings paralleled the suppression of virus replication and immune response recovery. Worsening of the MRI findings, with development of contrast enhancement, mass effect, and edema may be seen in some patients.39 This phenomenon is known as immune reconstitution syndrome (IRIS) and is the result of a post-treatment inflammatory reaction due to the immune reconstitutive effect. Atrophic changes and increased hypointensity on T1W images with concomitant low signal on FLAIR images in these patients represent leukomalacia and burnt-out PML lesions.

Cytomegalovirus Infection

This infection is caused by cytomegalovirus (CMV), a member of the herpesvirus family.



The most common imaging findings in patients with CMV encephalitis are cortical atrophy, periventricular enhancement, and diffuse white matter abnormalities.45 Periventricular enhancement is not pathognomonic; it has been described in cases of lymphoma, toxoplasmosis, and other infections. White matter disease occurs as a result of inflammation of subependymal region and spread of the infection to the adjacent astrocytes of the white matter with infectious demyelination.46,47 In six patients with pathologically confirmed CMV infection of the CNS, Hassine and associates found atrophy in three patients, subependymal nodular lesions without enhancement in two patients, and ventriculitis in one patient.48

Rarely, cerebral mass lesions due to CMV could be observed in AIDS patients. In one study, two cases of cerebral mass lesions due to CMV were described.49 In both cases, a large contrast-enhancing mass was seen in the frontal lobe, with surrounding edema. CMV infection can also be present as choroid plexitis. In one reported case, a contrast-enhanced CT scan showed marked enhancement of the slightly enlarged right plexus. MRI confirmed the findings and the absence of enhancement of the ependyma.50 The discrimination between HIV and CMVassociated CNS disease is often difficult using clinical and imaging findings. MRS could be potentially useful in such cases. In one study, MRS was used to distinguish HIV encephalitis from CMV encephalitis.51 The findings suggest that a larger choline signal and a smaller NAA signal could be inferred within the white matter abnormalities due to HIV encephalitis/encephalopathy compared with CMV encephalitis.

Prion Diseases

Prion diseases are rare progressive neurodegenerative disorders that affect both humans and animals and are caused by prions. They occur in humans as the various forms of Creutzfeldt-Jakob disease (sporadic [sCJD]; familial [fCJD], or variant [vCJD]), Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia, and kuru. Another name for these diseases is transmissible spongiform encephalopathies (TSEs).


Prion diseases are rare, with fewer than 2 per million individuals affected per year.52 The elderly population is most commonly affected, with a peak incidence between 60 and 64 years of age. Prion diseases have also been demonstrated in young individuals.53 The sporadic form of CJD seems to affect females more often than men (ratio: 2 : 1).54,55 The majority of cases of CJD (about 85%) occur as sporadic disease, and a smaller proportion of patients (5%-15%) develop CJD because of inherited mutations of the prion protein gene. These inherited forms include Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia.

Clinical Presentation

The sporadic form of CJD is characterized by rapidly progressive dementia. The patients suffer from myoclonic movements and both pyramidal (Babinski sign) and extrapyramidal symptoms (rigor, akinesia, choreatic movements).56 Isolated cerebellar symptoms as early manifestations occur in only 5%.55 The clinical features of vCJD include younger age at onset of disease and longer disease duration. Periodic sharp waves will be detected on electroencephalograms in cases of sCJD and will often be absent in vCJD cases. Common symptoms and signs in fatal familial insomnia include intractable insomnia, dysfunction of the autonomic system (hyperthermia, hypertension, tachycardia, tachypnea, hyperhidrosis), dementia, and motor paralysis.

Brain biopsy or autopsy is required to confirm the diagnosis. The detection of 14-3-3 protein in the CSF, an elevated concentration of neuron-specific enolase (NSE), and periodic sharp wave complexes on an electroencephalogram, along with clinical signs, usually allow for a probable diagnosis while the patient is still alive.5759




Typical MRI findings in sCJD are hyperintensity on T2W and FLAIR images in the cortex and basal ganglia (Fig. 42-5). Increased signal on diffusion-weighted imaging (DWI) and a low apparent diffusion coefficient (ADC) in the basal ganglia and cerebral cortex are also common.62 These findings are more frequently seen in the head of the caudate nuclei, the putamen, the thalamus, the striatum, and the cortical gray matter. It has been speculated that the increased signal on DWI is related to decreased water diffusion by the spongiform changes. A decrease in NAA and elevation of MI have been demonstrated in the frontal white matter in a patient with fCJD and in the parietal and frontal white matter in a case of sCJD using a short echo time and a single-voxel technique.63,64 Metabolic abnormalities have also been demonstrated in the pulvinar of the thalamus, with decreased NAA and significantly increased MI in vCJD.65,66


The characteristic MRI abnormality in vCJD is hyperintensity on T2W sequences in the pulvinar nuclei, called the “pulvinar sign.”68 MRS findings in vCJD are characterized by marked metabolic changes in the thalamus, decreased NAA, and increased MI, reflecting the pattern of gray matter signal abnormalities seen on T2W and FLAIR images.65,69

Rasmussen’s Encephalitis

Rasmussen’s encephalitis is an inflammatory/autoimmunologic, unilateral, cortical inflammation with tissue destruction.


An atrophic hippocampus and an enlarged perisylvian cortical area will be seen on pathologic examination.

According to the latest pathologic reports, Rasmussen’s encephalitis is the result of an autoimmune process with astrocytes as the primary target.71 A specific feature is astrocytic apoptosis and subsequent loss of astrocytes. In addition, proliferation of microglia, neuronal degeneration, and marked perivascular lymphocytic infiltration are present.

Herpes Simplex Encephalitis

Herpes simplex encephalitis (HSE) is a life-threatening disease caused by herpes simplex virus (HSV) infection of the CNS.


Jan 22, 2016 | Posted by in NEUROLOGICAL IMAGING | Comments Off on Other Infections of the Brain
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