A Case of Adult Influenza A Virus–Associated Encephalitis: Magnetic Resonance Imaging Findings

A 27-year-old man presented with fever, convulsive seizure, and sudden impairment of consciousness. Magnetic resonance imaging (MRI) abnormalities were found in the bilateral thalami, including the brain stem and white matter. The possibility of a previous influenza A virus infection was considered, and cerebrospinal fluid cells and interleukin-6 were elevated. The MRI findings closely resembled those found in cases of childhood acute necrotizing encephalopathy (ANE). The present case suggests that adult influenza A virus-associated encephalitis/encephalopathy or ANE can occur during winter influenza epidemics.     

Time-course of blood–brain barrier disruption in senescence-accelerated mouse prone 8 (SAMP8) mice

Senescence of the cerebrovascular system and an abnormal function of the blood–brain barrier have been related with Alzheimer's disease. We studied here the time-course of blood–brain barrier disruption in senescence-accelerated mouse prone 8 (SAMP8) mice, which is a murine model of senescence and is also considered a model of Alzheimer's disease. We used a previously described method that allows evaluating blood–brain barrier integrity by observing Evans blue extravasation from brain blood vessels. Three brain regions (cortex, hippocampus and hippocampal fissure) of SAMP8 brains were analyzed at 3, 6, 9, 12 and 15 months of age. Moreover, genetically related senescence-accelerated mouse resistant 1 (SAMR1) and ICR-CD1 mice were studied. Results indicate that Evans blue permeability in SAMP8 and SAMR1 increases from 6 to 15 months in the three studied regions. At 15 months of age, SAMP8 and SAMR1 mice showed higher Evans blue extravasation in CA1 and Fissure than ICR-CD1 mice. Further studies are required to understand the senescence process in SAMR1 mice, as blood–brain barrier alterations in old age have unexpectedly been observed. On the other hand, as blood–brain barrier permeability in SAMP8 mice increases with age, blood–brain barrier alterations may contribute to the cerebral pathology observed in this strain.     

Rapid and reversible enhancement of blood–brain barrier permeability using lysophosphatidic acid

The present study characterizes the effects of lysophosphatidic acid (LPA) on blood–brain barrier (BBB) permeability focusing specifically on the time of onset, duration, and magnitude of LPA-induced changes in cerebrovascular permeability in the mouse using both magnetic resonance imaging (MRI) and near infrared fluorescence imaging (NIFR). Furthermore, potential application of LPA for enhanced drug delivery to the brain was also examined by measuring the brain accumulation of radiolabeled methotrexate. Exposure of primary cultured brain microvessel endothelial cells (BMECs) to LPA produced concentration-dependent increases in permeability that were completely abolished by clostridium toxin B. Administration of LPA disrupted BBB integrity and enhanced the permeability of small molecular weight marker gadolinium diethylenetriaminepentaacetate (Gd-DTPA) contrast agent, the large molecular weight permeability marker, IRdye800cwPEG, and the P-glycoprotein efflux transporter probe, Rhodamine 800 (R800). The increase in BBB permeability occurred within 3 minutes after LPA injection and barrier integrity was restored within 20 minutes. A decreased response to LPA on large macromolecule BBB permeability was observed after repeated administration. The administration of LPA also resulted in 20-fold enhancement of radiolabeled methotrexate in the brain. These studies indicate that administration of LPA in combination with therapeutic agents may increase drug delivery to the brain.     

17β-estradiol attenuates breakdown of blood-brain barrier and hemorrhagic transformation induced by tissue plasminogen activator in cerebral ischemia

Tissue plasminogen activator (tPA) remains the only approved thrombolytic agent for the early treatment of ischemic stroke. However, treatment with tPA may lead to disruption of the blood–brain barrier and hemorrhagic transformation. 17β-estradiol (E2) has demonstrated efficacy in reduction of infarct volume in ischemic stroke models. The effects of acute administration of E2 on permeability of the blood–brain barrier and its ability to prevent hemorrhagic transformation in ischemic rats treated with tPA have not previously been studied. Here, we show that neurological deficits, brain water content, and Evan's blue extravasation were increased in ovariectomized female Wistar rats treated with tPA and attenuated in rats receiving E2 + tPA. We also show that intracerebral hemoglobin and matrix metalloproteinase-9 activity were elevated with tPA treatment, and these increases were reduced by E2 treatment. Taken together, these data demonstrate that acute administration of E2 is capable of ameliorating some of the adverse effects of tPA administration, including the increase of matrix metalloproteinase-9 activity, blood–brain barrier permeability, and hemorrhagic transformation. These findings suggest a potential role for estrogen in thrombolytic treatment for ischemic stroke.     

Neuroimaging of thalamic tumors in children

INTRODUCTION: Thalamic tumors are typical deep brain tumors; their incidence is not precisely known because of the different definition criteria. However, taking only lesions arising in the thalami into consideration (and excluding those secondarily involving the thalami from adjacent structures) approximately 40% of thalamic tumors affect patients under 18 years of age and thalamic neoplasms account for 2-5% of all intracranial tumors in children. MATERIALS AND METHODS: In the present paper we have focused attention on the neuroimaging features of thalamic tumors in a pediatric population; based upon personal experience, we suggest a rational neuroradiological approach to the diagnostic evaluation, describe CT and MRI findings of the most common tumors, and attempt to define basic patterns in order to provide the most reliable "pathological" diagnosis.     

Neuropsychological outcomes of childhood acute necrotizing encephalopathy

Acute necrotizing encephalopathy (ANE) is a rare form of acute encephalopathy, predominantly occurring in childhood, which has a typical radiological phenotype including bilateral, symmetrical, diffusion-restricted lesions of the thalami; posterior putamen; cerebellum; and brainstem. To date, no study has systematically examined the long-term cognitive and psychological impact of ANE. The current study describes the neuropsychological outcomes of three paediatric cases of ANE, ranging from 18 months to 10 years post ANE. All three cases displayed inattention, fine motor difficulties and anxiety. Social difficulties were also reported in all cases. The severity of long-term impairment was associated with acute presentation, as well as convalescent neuroimaging. These findings highlight the need for detailed neuropsychological assessment and long-term rehabilitation.     

Spatial diversity of blood–brain barrier alteration and macrophage invasion in experimental autoimmune encephalomyelitis: A comparative MRI study

Inflammation plays a central role in the development of numerous disorders of the central nervous system (CNS) such as multiple sclerosis (MS). For a long time it was assumed that recruitment of macrophages into the CNS and breakdown of the blood–brain barrier (BBB) are closely linked. In the present study we challenge this concept. We used small superparamagnetic iron oxide particles (SPIO)-enhanced T2-weighted (T2-w) magnetic resonance imaging (MRI) on a routine 1.5 T MRI unit to follow macrophage infiltration in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. After an initial SPIO-enhanced MRI, gadofluorine M (Gf), an experimental contrast agent which proved to be more sensitive in detecting BBB leakage than gadolinium (Gd)–DTPA (Bendszus, M., Ladewig, G., Jestaedt, L., Misselwitz, B., Solymosi, L., Toyka, K.V., Stoll, G., Gadofluorine-M enhancement allows more sensitive detection of inflammatory CNS lesions than T2-w imaging: a quantitative MRI study. Brain 2008; 1-12), was applied to the same animals followed by a second scan. Areas with SPIO-induced signal loss on T2-w MRI indicative of recent macrophage infiltration were matched with areas showing Gf enhancement as a measure of BBB disturbance. Overall 87 EAE lesions showed iron-related signal loss, while 57 lesions showed Gf enhancement. By direct comparison we could detect concomitant SPIO-induced signal loss and Gf enhancement only in a small minority of lesions. In conclusion, our findings show macrophage infiltration in the CNS during EAE in areas with a closed BBB for humoral factors. This holds true despite the use of a more sensitive MR contrast agent for BBB disruption than Gd-DTPA. Our experimental observations may have implications for disease monitoring in MS patients by MRI which guides treatment decisions.     

Varicella-associated acute necrotizing encephalopathy with a good prognosis

A patient with acute necrotizing encephalophathy (ANE) following varicella infection with a good prognosis is reported. A somatosensory evoked magnetic field (SEF) study using a 37-channel-magnetoencephalography system demonstrated normal latency and strength of the first component (N20m) elicited by median nerve stimulation, despite bilateral symmetrical thalamic lesions on MRI. The normal SEF findings and the good prognosis suggested a reversible breakdown of the blood-brain barrier, and an edematous process as the brain pathology. Furthermore, our results support the idea of distinct generators for the three earliest cortical SEF components (N20m, P30m, N45m).     

Spinal cord biopsy findings of anti‐aquaporin‐4 antibody‐negative recurrent longitudinal myelitis in a patient with sicca symptoms and hepatitis C viral infection

We describe the pathological features of a spinal cord biopsy from a 69‐year‐old woman with anti‐aquaporin‐4 antibody‐negative recurrent longitudinal myelitis. Spinal cord MRI showed T2 high‐intensity lesions with strong gadolinium enhancement, when episodes of sensory‐motor impairment were repeated. The radiological abnormality was corrected by corticosteroid administration, but improvement of the symptoms was minimal. Although the patient had sicca symptoms and fulfilled four of the diagnostic criteria for Sjögren syndrome, the diagnosis was excluded, because of infection with hepatitis C virus, an exclusion criterion of Sjögren syndrome. In the spinal cord lesions, necrotic changes affected both myelin and axons. Infiltrating lymphocytes were predominantly T‐cells. The proliferation of small vessels with hyalinization and concomitant occlusive change was remarkable. These pathological findings resembled those previously reported in Sjögren syndrome. Ultrastructurally, the endothelial cells of the small vessels showed features of activated cells and contained vesiculo‐tubular structures in the cytoplasm, indicating that increased blood‐brain barrier (BBB) permeability might contribute to pathogenesis. We speculated that increased BBB permeability and T‐cell entry in the spinal parenchyma triggered pathological reactions resulting in necrotic changes in the spinal cord. Obstruction of small vessels might add ischemic damage to the lesions. The clinical course and pathological findings indicated that damage progressed rapidly in the spinal cord and was irreversible. The lesions apparently differed from typical demyelination plaques. Faced with such spinal cord lesions, a preventive therapeutic approach is necessary to avoid attack‐associated disability.     

Thrombosis of the vein of Galen: a case report

Thrombosis of the deep cerebral venous system is a rare entity. We report a case of 68-year-old male presenting with headache, left side weakness, and alteration of consciousness at admission. He was diagnosed as deep cerebral venous thrombosis (DCVT) of the vein of Galen on the basis of brain magnetic resonance imaging (MRI) findings. Anticoagulant therapy with heparin was constituted and he made a good recovery. DCVT often involves bilateral thalami and sometimes basal ganglia with obscure clinical manifestations. Therefore, early diagnosis may not be always straightforward. Brain MRI findings with unique "circular" region of signal change in bilateral thalami and basal ganglia can be very helpful for a proper diagnosis. Although early anticoagulation therapy is usually recommended, the optimal treatment of this rare disease needs further investigation.     

A novel adult case of acute necrotizing encephalopathy of childhood with bilateral symmetric thalamic lesions]

This report describes a 46-year-old Japanese woman with bilateral symmetric thalamic necrosis. The unusual radiologic findings are discussed in relation with acute necrotizing encephalopathy (ANE) of childhood, a rare disease proposed by Mizuguchi et al. ANE affects young children and the incidence is highest between 6 and 18 months of ages. There is only one report of an adult case. The acute stage pathology in ANE can be summarized as acute edema and necrosis involving both gray and white matter by local breakdown of the blood-brain barrier. The radiologic findings in our case were similar to those in ANE of childhood. Though the pathogenesis between our adult case and ANE of childhood might be different, severe hypoalbuminea in our case could cause the alteration of permeability of the thalamic vessels, which might accelerate breakdown of the blood-brain barrier in the thalamus.     

Brain metastases

Brain metastases are frequent, accounting for 20% of all brain tumours. The most common primary tumours responsible for brain metastases are lung cancer in man and breast cancer in women. Most metastases are located at the grey matter-white matter junction, in junctional vascular territories and in the rolandic region. Although non-specific, MRI is the most sensitive neuroradiological method for the lesions, especially when accompanied by gadolinium injection. MRI must absolutely be performed before surgical treatment, as gadolinium might detect other metastatic lesions or show metastatic tumours so small that they were not visible at computerized tomography (CT).     

Bilateral facial nerve enhancement demonstrated by magnetic resonance imaging in Guillain–Barre Syndrome

Guillain–Barré syndrome (GBS) is an acute inflammatory demyelinating peripheral nerve disorder. It is known that gadolinium enhancement on magnetic resonance imaging (MRI) reflects alteration of the blood–nerve barrier secondary to inflammation. Enhancement of the cauda equina roots with gadolinium on lumbosacral magnetic resonance imaging have been demonstrated in several reports. Although about 50% of GBS patients clinically exhibit facial nerve involvement, it has never been demonstrated on MRI. We aimed to observe facial nerve involvement in a GBS patient who has prominent facial diplegia. With the guidance of the literature, we predict that MRI in selected GBS patients may be an adjunct tool for the clinician in both diagnosis and monitoring the treatment response.     

Primary central nervous system lymphoma initially mimicking lymphomatosis cerebri: An autopsy case report

A 59‐year‐old immunocompetent man was admitted to our hospital because of progressive dementia with concomitant bilateral uveitis. The first brain MRI revealed diffuse hyperintense lesions in the cerebral white matter of both hemispheres on a T2‐weighted image and fluid‐attenuated inversion recovery image. However, another MRI taken more than 1 month later revealed enhanced cohesive mass lesions in the bilateral thalami, in addition to the white matter lesions. The white matter lesions were slightly hyperintense on a diffusion‐weighted image and apparent diffusion coefficient map image, suggesting vasogenic edema. One year after the onset of uveitis, he died of respiratory failure. Pathological diagnosis was diffuse large B‐cell lymphoma with perivascular proliferation and diffuse scattered infiltration in the cerebrum and brainstem. Microscopically, cohesive mass lesions in the bilateral thalami were a massive cluster of lymphoma cells. This is a case of primary CNS lymphoma (PCNSL) mimicking ‘lymphomatosis cerebri (LC)’ at first but later exhibiting typical mass lesions, giving rise to the possibility that cases of LC might unmask features of regular lymphomas in their later course more often than believed thus far.     

Nitric oxide donor-induced increase in permeability of the blood–brain barrier

The goal of the present study was to determine the effect of nitric oxide (NO) donors on the permeability of the blood–brain barrier in vivo. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood–brain barrier was quantitated by calculating the clearance of fluorescent-labeled dextran (M_w=10 000 Da; FITC–dextran-10K) during suffusion with vehicle, S-nitroso-N-acetylpenicillamine (SNAP; 100 μM) and 3-morpholinosydnonimin (SIN-1; 100 μM). In addition, we examined changes in arteriolar diameter during suffusion with vehicle, SNAP and SIN-1. During suffusion with vehicle, clearance of FITC–dextran-10K from pial vessels and diameter of pial arterioles remained relatively constant during the experimental period. In contrast, suffusion with SNAP or SIN-1 markedly increased clearance of FITC–dextran-10K from the cerebral microcirculation and produced a rapid, sustained dilatation of pial arterioles. Thus, NO donors increase the permeability of the blood–brain barrier and produce pronounced dilatation of cerebral arterioles. In light of evidence suggesting that NO donors may produce their effect by the simultaneous release of NO and superoxide anion to form peroxynitrite, we elected to examine the role of superoxide anion in increases in permeability of the blood–brain barrier in response to SNAP and SIN-1. We found that suffusion with tiron (1 mM) did not alter basal permeability of the blood–brain barrier, but significantly inhibited increases in permeability of the blood–brain barrier in response to SNAP and SIN-1. In addition, tiron did not alter baseline diameter of cerebral arterioles, or SNAP- and SIN-1-induced cerebrovasodilatation. The findings of the present study suggest that NO donors produce an increase in permeability of the blood–brain barrier which appears to be related to the presence of NO and superoxide anion, to presumably form peroxynitrite. We suggest that increases in NO formation observed during brain trauma may contribute to disruption of the blood–brain barrier.     

Brain MRI in global hypoxia–ischemia: a map of selective vulnerability

Hypoxic-ischemic injury to the brain is a devastating occurrence that frequently results in death or profound long-term neurologic disability. In this report, we describe the neuroradiological findings of a patient suffering from a global brain hypoxic-ischemic injury. Our findings clearly display that the areas of the brain with the highest metabolic activity, such as basal ganglia, thalami, and occipital and perirolandic cortex, are most susceptible to hypoxic injury. The MRI images delineate a map of the brain areas with selective vulnerability to hypoxia.     

Magnetic resonance brain tumor imaging in canine glioma

This study investigates a canine model of experimental brain tumor. Particularly addressed was the usefulness of gadolinium contrast-enhanced MRI for differentiating brain tumor tissue from cerebral edema. Cultured canine glioma cells were injected into the left hemispheres of six adult mongrel dogs. All dogs developed brain tumors. Serum samples drawn prior to and serially after tumor inoculation showed development of antibodies reactive to the tumor. All tumors were visualized with MRI. Contrast-enhanced T1-weighted imaging was the most sensitive with gadolinium producing tumor enhancement due to blood-brain barrier breakdown. Gross and microscopic autopsy findings correlated well with MRIs.     

Intravascular lymphomatosis: contribution of cerebral MRI findings to diagnosis.

Intravascular lymphomatosis (IL) is a rare variant of non-Hodgkin's lymphoma with an unusual predilection for the central nervous system (CNS). Most cases are not diagnosed until postmortem because of variable clinical presentation and nonspecific laboratory findings. Neuroimaging findings vary widely and range from diffuse involvement of the deep white matter to infarct-like lesions. Cerebral magnetic resonance imaging (MRI) may show parenchymal and meningeal gadolinium enhancement. The authors describe brain MRI findings of linear, punctate, and patchy enhancement suggestive of CNS IL in two patients confirmed by brain biopsy/histologic studies. High index of clinical suspicion and careful interpretation of MRI (including gadolinium contrast studies) may contribute to premortem diagnosis and early intervention of this often-missed disease.     

多发性硬化脑内病灶MRI典型及不典型表现:附82例MRI分析

目的分析我国多发性硬化病例典型及不典型影像学改变。方法回顾经McDonald诊断标准明确诊断的82例多发性硬化患者的头部MRI检查结果,分析病灶部位、大小、数目、形状、信号强度及强化方式等。结果我国多发性硬化的典型影像学表现:（1）病灶部位以脑室旁（62例,75.61%）及幕上深部白质（55例,67.07%）多见。（2）病灶数目多在10个以上（62例,75.61%）。（3）病灶直径以≤1 cm为主（62例,75.61%）,>5 cm次之（23例,28.05%）。（4）信号强度及强化特征为T₁WI平扫呈等或略低信号,T₁WI高信号,PDwI高于脑脊液中水信号;T₁WI增强图像黑洞从微小至大片状均可见,形状多呈类圆形或条片状;<1 cm病灶显示结节状强化,1～5 cm病灶一般呈环状强化,>5 cm病灶以边缘强化或内部呈不规则环状强化为主,皮质病灶多见弓状强化。我国多发性硬化的不典型影像学表现为:病灶较大,最大直径>5 cm（23例,28.05%）;强化显著且强化持续时间较长;脑干病灶多见（61例,74.39%）。结论侧脑室旁或深部白质内多发小病灶是多发性硬化的典型MRI表现;侧脑室旁病灶致侧脑室变形、大脑凸面的微小黑洞及侧脑室边缘的条片状黑洞,以及近皮质或围绕侧脑室颞角的弓状强化具有重要诊断价值。病灶大、强化显著及脑干病灶多见,是我国多发性硬化不同于欧美地区的主要表现。     

多发性硬化脑内病灶MRI典型及不典型表现：附82例MR1分析

目的分析我国多发性硬化病例典型及不典型影像学改变。方法回顾经McDonald诊断标准明确诊断的82例多发性硬化患者的头部MRI检查结果,分析病灶部位、大小、数目、形状、信号强度及强化方式等。结果我国多发性硬化的典型影像学表现：（1）病灶部位以脑室旁（62例,75．61％）及幕上深部白质（55例,67．07％）多见。（2）病灶数目多在10个以上（62例,75．61％）。（3）病灶直径以≤1cm为主（62例,75．61％）,〉5cm次之（23例,28．05％）。（4）信号强度及强化特征为T1WI平扫呈等或略低信号,T2WI高信号,PDWI高于脑脊液中水信号;T1WI增强图像黑洞从微小至大片状均可见,形状多呈类圆形或条片状;〈1cm／病灶显示结节状强化,1～5cm病灶一般呈环状强化,〉5cm病灶以边缘强化或内部呈不规则环状强化为主,皮质病灶多见弓状强化。我国多发性硬化的不典型影像学表现为：病灶较大,最大直径〉5cm（23例,28．05％）;强化显著且强化持续时间较长;脑干病灶多见（61例,74．39％）。结论侧脑室旁或深部白质内多发小病灶是多发性硬化的典型MRI表现;侧脑室旁病灶致侧脑室变形、大脑凸面的微小黑洞及侧脑室边缘的条片状黑洞,以及近皮质或围绕侧脑室颞角的弓状强化具有重要诊断价值。病灶大、强化显著及脑干病灶多见,是我国多发性硬化不同于欧美地区的主要表现。