Perivascular Lymphocytic Cuffing Research Articles

Mouse Adapted SARS-CoV-2 (MA10) Viral Infection Induces Neuroinflammation in Standard Laboratory Mice.

Increasing evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection impacts neurological function both acutely and chronically, even in the absence of pronounced respiratory distress. Developing clinically relevant laboratory mouse models of the neuropathogenesis of SARS-CoV-2 infection is an important step toward elucidating the underlying mechanisms of SARS-CoV-2-induced neurological dysfunction. Although various transgenic models and viral delivery methods have been used to study the infection potential of SARS-CoV-2 in mice, the use of commonly available laboratory mice would facilitate the study of SARS-CoV-2 neuropathology. Herein we show neuroinflammatory profiles of immunologically intact mice, C57BL/6J and BALB/c, as well as immunodeficient (Rag2-/-) mice, to a mouse-adapted strain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 (MA10)). Our findings indicate that brain IL-6 levels are significantly higher in BALB/c male mice infected with SARS-CoV-2 MA10. Additionally, blood-brain barrier integrity, as measured by the vascular tight junction protein claudin-5, was reduced by SARS-CoV-2 MA10 infection in all three strains. Brain glial fibrillary acidic protein (GFAP) mRNA was also elevated in male C57BL/6J infected mice compared with the mock group. Lastly, immune-vascular effects of SARS-CoV-2 (MA10), as measured by H&E scores, demonstrate an increase in perivascular lymphocyte cuffing (PLC) at 30 days post-infection among infected female BALB/c mice with a significant increase in PLC over time only in SARS-CoV-2 MA10) infected mice. Our study is the first to demonstrate that SARS-CoV-2 (MA10) infection induces neuroinflammation in laboratory mice and could be used as a novel model to study SARS-CoV-2-mediated cerebrovascular pathology.

Subtle vascular and astrocytic changes in the brain of coronavirus disease 2019 (COVID-19) patients.

Background and purposeIn the central nervous system, a multitude of changes have been described associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, such as microglial activation, perivascular lymphocyte cuffing, hypoxic‐ischaemic changes, microthrombosis, infarcts or haemorrhages. It was sought here to assess the vascular basement membranes (vBMs) and surrounding perivascular astrocytes for any morphological changes in acute respiratory syndrome (coronavirus disease 2019, COVID‐19) patients.MethodsThe light microscopy morphology of the vBMs and perivascular astrocytes from brains of 14 patients with confirmed SARS‐CoV‐2 infection was analysed and compared to four control patients utilizing fluorescent immunohistochemistry for collagen IV and astrocytes (GFAP), endothelia (CD31), tight junction 1 (TJ1) adhesion protein, as well as the aquaporin 4 (AQP4) water channel. On 2D and 3D deconvoluted images from the cortex and white matter, vessel densities, diameters, degree of gliosis, collagen IV/GFAP and GFAP/AQP4 colocalizations were calculated, as well as the fractal dimension of astrocytes and vBMs viewed in tangential planes.ResultsFractal dimension analysis of the GFAP‐stained astrocytes revealed lower branching complexities and decreased GFAP/collagen IV colocalization for COVID‐19 patients. Interestingly, vBMs showed significantly increased irregularities (fractal dimension values) compared to controls. Vessel diameters were increased in COVID‐19 cases, especially for the white matter, TJ1 protein decreased its colocalization with the endothelia, and AQP4 reduced its co‐expression in astrocytes.ConclusionsOur data on the irregularity of the basement membranes, loss of endothelial tight junction, reduction of the astrocyte end‐feet and decrease of AQP4 suggest subtle morphological changes of the blood–brain barrier in COVID‐19 brains that could be linked with indirect inflammatory signalling or hypoxia/hypercapnia.

Evidence of Hearing Loss and Unrelated Toxoplasmosis in a Free-Ranging Harbour Porpoise (Phocoena phocoena).

Simple SummaryEvidence of hearing impairment was identified in a female harbour porpoise (Phocoena phocoena) on the basis of inner ear analysis. The animal live stranded on the Dutch coast at Domburg in 2016 and died a few hours later. Ultrastructural examination of the inner ear revealed evidence of sensory cell loss, which is compatible with noise exposure. In addition, histopathology also revealed multifocal necrotising protozoal encephalitis. A diagnosis of toxoplasmosis was confirmed by positive staining of tissue with anti-Toxoplasma gondii antibodies; however, T. gondii tachyzoites were not observed histologically in any of the examined tissues. This is the first case of presumptive noise-induced hearing loss and demonstration of T. gondii cysts in the brain of a free-ranging harbour porpoise from the North Sea.Evidence of hearing impairment was identified in a harbour porpoise (Phocoena phocoena) on the basis of scanning electron microscopy. In addition, based on histopathology and immunohistochemistry, there were signs of unrelated cerebral toxoplasmosis. The six-year old individual live stranded on the Dutch coast at Domburg in 2016 and died a few hours later. The most significant gross lesion was multifocal necrosis and haemorrhage of the cerebrum. Histopathology of the brain revealed extensive necrosis and haemorrhage in the cerebrum with multifocal accumulations of degenerated neutrophils, lymphocytes and macrophages, and perivascular lymphocytic cuffing. The diagnosis of cerebral toxoplasmosis was confirmed by positive staining of protozoa with anti-Toxoplasma gondii antibodies. Tachyzoites were not observed histologically in any of the examined tissues. Ultrastructural evaluation of the inner ear revealed evidence of scattered loss of outer hair cells in a 290 µm long segment of the apical turn of the cochlea, and in a focal region of ~ 1.5 mm from the apex of the cochlea, which was compatible with noise-induced hearing loss. This is the first case of concurrent presumptive noise-induced hearing loss and toxoplasmosis in a free-ranging harbour porpoise from the North Sea.

Olfactory bulb SARS-CoV-2 infection is not paralleled by the presence of virus in other central nervous system areas.

Olfactory bulb SARS-CoV-2 infection is not paralleled by the presence of virus in other central nervous system areas.

NIMG-62. AMPHETAMINE-ASSOCIATED CNS VASCULITIS MASQUERADING AS TUMOUR

Abstract Amphetamine-associated CNS vasculitis is controversial. There are few reports but none as a tumor mimic to our knowledge. We describe a pathology-proven, amphetamine-associated CNS vasculitis resembling a tumor. A 41-year-old man presented with six weeks of progressive confusion and left-sided weakness. CT head reported a right thalamic mass with vasogenic edema. Laboratory tests were unremarkable except for cannabinoids and amphetamine in urine. MRI brain showed enhancement in right frontotemporal lobe, basal ganglia, and thalamus concerning for glioblastoma multiforme. After high-dose IV dexamethasone, an initial biopsy showed reactive gliosis, perivascular lymphocytic cuffing by CD3+, rare CD20+ cells and no infection. He continued to decline. MRI 22 days after admission showed increased T2/FLAIR hyperintensity, multifocal areas of enhancement, microhemorrhages, and ischemia. High-grade glioma, lymphoma and infectious encephalitis remained on differentials. Treatment included broad-spectrum antibiotics and acyclovir. Biopsy on 23rd day showed reactive gliosis with parenchymal macrophage infiltration and perivascular cuffing with mixed inflammatory infiltrates. CSF: slightly elevated WBCs (8/µL), elevated protein (139mg/dL), normal glucose, and no infection. MRI whole spine and CT body were unremarkable. The patient was transferred to MDACC 5.5 weeks after initial presentation. He was alert with expressive aphasia, right gaze preference, left hemiplegia, and right hemiparesis. He underwent a right anterior temporal lobectomy. Pathology showed extensive cortical laminar and white matter necrosis with macrophage infiltration and microglial activation. In areas of the preserved cortex, vasculocentric lymphocytic aggregates were present and reticulin staining showed lymphocytic infiltration of the vascular walls. Immunophenotyping (CD3, CD20) showed an almost pure T-cell population. The predominance of intramural T-lymphocytes reflected a vasculitic process. The final diagnosis was cerebral vasculitis with subacute infarction. The patient died six days later. The autopsy findings were identical to the previous resection without evidence of systemic inflammation.

Simian Immunodeficiency Virus-Infected Memory CD4+ T Cells Infiltrate to the Site of Infected Macrophages in the Neuroparenchyma of a Chronic Macaque Model of Neurological Complications of AIDS.

Simian immunodeficiency virus (SIV)-infected nonhuman primates can serve as a relevant model for AIDS neuropathogenesis. Current SIV-induced encephalitis (SIVE)/neurological complications of AIDS (neuroAIDS) models are generally associated with rapid progression to neuroAIDS, which does not reflect the tempo of neuroAIDS progression in humans. Recently, we isolated a neuropathogenic clone, SIVsm804E-CL757 (CL757), obtained from an SIV-infected rhesus macaque (RM). CL757 causes a more protracted progression to disease, inducing SIVE in 50% of inoculated animals, with high cerebral spinal fluid viral loads, multinucleated giant cells (MNGCs), and perivascular lymphocytic cuffing in the central nervous system (CNS). This latter finding is reminiscent of human immunodeficiency virus (HIV) encephalitis in humans but not generally observed in rapid progressor animals with neuroAIDS. Here, we studied which subsets of cells within the CNS were targeted by CL757 in animals with neurological symptoms of SIVE. Immunohistochemistry of brain sections demonstrated infiltration of CD4+ T cells (CD4) and macrophages (MΦs) to the site of MNGCs. Moreover, an increase in mononuclear cells isolated from the brain tissues of RMs with SIVE correlated with increased cerebrospinal fluid (CSF) viral load. Subset analysis showed a specific increase in brain CD4+ memory T cells (Br-mCD4), brain-MΦs (Br-MΦs), and brain B cells (Br-B cells). Both Br-mCD4s and Br-MΦs harbored replication-competent viral DNA, as demonstrated by virus isolation by coculture. However, only in animals exhibiting SIVE/neuroAIDS was virus isolated from Br-MΦs. These findings support the use of CL757 to study the pathogenesis of AIDS viruses in the central nervous system and indicate a previously unanticipated role of CD4s cells as a potential reservoir in the brain.IMPORTANCE While the use of combination antiretroviral therapy effectively suppresses systemic viral replication in the body, neurocognitive disorders as a result of HIV infection of the central nervous system (CNS) remain a clinical problem. Therefore, the use of nonhuman primate models is necessary to study mechanisms of neuropathogenesis. The neurotropic, molecular clone SIVsm804E-CL757 (CL757) results in neuroAIDS in 50% of infected rhesus macaques approximately 1 year postinfection. Using CL757-infected macaques, we investigate disease progression by examining subsets of cells within the CNS that were targeted by CL757 and could potentially serve as viral reservoirs. By isolating mononuclear cells from the brains of SIV-infected rhesus macaques with and without encephalitis, we show that immune cells invade the neuroparenchyma and increase in number in the CNS in animals with SIV-induced encephalitis (SIVE). Of these cells, both brain macrophages and brain memory CD4+ T cells harbor replication-competent SIV DNA; however, only brain CD4+ T cells harbored SIV DNA in animals without SIVE. These findings support use of CL757 as an important model to investigate disease progression in the CNS and as a model to study virus reservoirs in the CNS.

T lymphocytes and cytotoxic astrocyte blebs correlate across autism brains.

Autism spectrum disorder (ASD) affects 1 in 59 children, yet except for rare genetic causes, the etiology in most ASD remains unknown. In the ASD brain, inflammatory cytokine and transcript profiling shows increased expression of genes encoding mediators of the innate immune response. We evaluated postmortem brain tissue for adaptive immune cells and immune cell-mediated cytotoxic damage that could drive this innate immune response in the ASD brain. Standard neuropathology diagnostic methods including histology and immunohistochemistry were extended with automated image segmentation to quantify identified pathologic features in the postmortem brains. We report multifocal perivascular lymphocytic cuffs contain increased numbers of lymphocytes in ~65% of ASD compared to control brains in males and females, across all ages, in most brain regions, and in white and gray matter, and leptomeninges. CD3+ T lymphocytes predominate over CD20+ B lymphocytes and CD8+ over CD4+ T lymphocytes in ASD brains. Importantly, the perivascular cuff lymphocyte numbers correlate to the quantity of astrocyte-derived round membranous blebs. Membranous blebs form as a cytotoxic reaction to lymphocyte attack. Consistent with multifocal immune cell-mediated injury at perivascular cerebrospinal fluid (CSF)-brain barriers, a subset of white matter vessels have increased perivascular space (with jagged contours) and collagen in ASD compared to control brains. CSF-brain barrier pathology is also evident at cerebral cortex pial and ventricular ependymal surfaces in ASD. The findings suggest dysregulated cellular immunity damages astrocytes at foci along the CSF-brain barrier in ASD. ANN NEUROL 2019;86:885-898.

Intragastric and intracoelomic injection challenge models of tilapia lake virus infection in Nile tilapia (Oreochromis niloticus L.) fingerlings.

To gain a better understanding of the pathogenesis of tilapia lake virus (TiLV) infections in Nile tilapia (Oreochromis niloticus), fingerlings were challenged with a single dose of 1×104 TCID50 /fish of TiLV utilizing intracoelomic/intraperitoneal (ICch ) or intragastric (IGch ) routes. Acute mortalities were present in both groups, reaching 70 and 40% in ICch and IGch after 10days, respectively. Challenged fish presented erratic swimming, lethargy, anorexia, exophthalmia and cutaneous petechiae and ecchymoses. Histological changes in challenged groups included syncytial formation, intracytoplasmic inclusion bodies and multifocal hepatocellular degeneration and necrosis. In addition, multifocal areas of mild proliferation of glial cells and lymphocytic perivascular cuffing were observed in the brain of exposed challenged groups. TiLV RNA was detected in gills and faeces of challenged fish using quantitative reverse transcriptase-PCR, as well as in the tank water holding challenged fish. Moreover, TiLV RNA was detected in scrolls obtained from formalin-fixed paraffin-embedded tissue blocks from challenged fish. Results from this study suggest that IG methods represent an additional method to study the pathogenesis of the disease in this species, as it results in infection and diseases as in naturally occurring cases and does not bypass important mucosal immune responses as injectable routes do.

DETECTION OF DNA ALTERATIONS IN MUSCOVY DUCKS (CAIRINA MOSCHATA) NATURALLY INFECTED WITH HIGHLY PATHOGENIC AVIAN INFLUENZA VIRUS SUBTYPE H5N1

Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 is circulating in Egypt since 2006, with escalating apprehension about its possibility to become more transmissible amongst humans. In this study, three serial outbreaks of HPAIV H5N1 in domestic Muscovy ducks in Sharkia Governorate, Egypt were investigated. Nervous signs with 62% mortality were observed in Muscovy ducklings. Gross examination revealed severely congested meningeal vessels, hemorrhages on the duodenum, pancreas, and coronary fat. Perivascular lymphocytic cuffing, gliosis and vacuolation of the neuropil were observed in the brain microscopically. Viral antigens were identified in the neurons and the glial cells of the cerebral cortex, submucosal Meissner's plexus neurons of the intestine and the hepatic Kupffer cells by immunohistochemistry. The HPAIV subtype H5N1 was isolated from different duck tissues in 66.7% of examined duck samples. Using RAPD-PCR fingerprinting, there were different patterns in the DNA of Muscovy ducks naturally infected with AIV (24, 48 and 72 hours post appearance of clinical signs) compared to uninfected birds. Differences in RAPD-PCR profiles between infected and uninfected ducks, and genomic instability percent (37.7%±1.76) pointed to the incidence of DNA alterations induced at 24 hours following the appearance of clinical signs. Further in vivo and in vitro experiments need to be done to determine the relative importance of these findings.

A Fatal Case of Louping-ill in a Dog: Immunolocalization and Full Genome Sequencing of the Virus

SummaryLouping-ill (LI), caused by louping-ill virus (LIV), results in a frequently fatal encephalitis primarily affecting sheep and red grouse (Lagopus lagopus scotica), but it does occur in other species. An adult male Border collie dog was definitively diagnosed with fatal LI and the lesion profile, LIV antigen distribution and full genome sequence of the LIV responsible were investigated to determine if this differed significantly from sheep-derived LIV. No gross lesions were present. The histological lesions were confined to the central nervous system and comprised of lymphocytic perivascular cuffs, glial foci, neuronal necrosis and neuronophagia. Immunolocalization of viral antigen showed small amounts present in neurons only. These histological and immunohistochemical findings were similar to those reported in affected sheep. Compared with published full genome sequences of sheep-derived LIV, only very minor differences were present and phylogenetically the virus clustered individually between a subclade containing Scottish strains, LIV 369/T2 and G and another subclade containing an English isolate LIV A. The LIV isolated from the dog shares a common progenitor with LIV A. These findings suggest there is no canine-specific LIV strain, dogs are susceptible to sheep-associated strains of LI and with the increase in tick prevalence, and therefore exposure to LIV, a safe, effective vaccine for dogs may be required.

Update on Neurological Manifestations of HTLV-1 Infection.

The human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects 10-20 million persons around the world. Initially associated with the hematological malignancy adult T cell leukemia/lymphoma (ATLL), HTLV-1 is also the cause of a chronic progressive myelopathy named "HTLV-1-associated myelopathy/tropical spastic paraparesis" (HAM/TSP). HAM/TSP arises as the tip of the iceberg of an assortment of neurological syndromes triggered by the virus such as inflammatory myopathies, polyneuropathies, amyotrophic lateral sclerosis (ALS)-like syndromes, dysautonomia, and cognitive impairment. HAM/TSP typifies a chronic progressive spastic paraparesis with neurogenic bladder and minimal sensory signs. The neuropathology of HAM/TSP is concentrated in the thoracic spinal cord and is typically biphasic. Initially, there is a perivascular lymphocytic cuffing and mild parenchymal mononuclear infiltrates. Subsequently, this is replaced by gliosis and scarring. The neuropathogenesis of HTLV-1 is still partially understood. At present, the therapy of HAM/TSP remains basically symptomatic.

PM-17 * INTRACEREBRAL IFN- DOES NOT ENHANCE THE RESPONSE TO VACCINE IMMUNOTHERAPY FOR CANINE GLIOMA

Due to the complexity of human tumor environment and host immune interactions, the majority of successful brain cancer therapies in rodent models fail to show the same efficacy when translated to human patients. Pet dogs with spontaneous glioma recapitulate important features of human disease and we have used this more representative model to assess the response to vaccine immunotherapy with and without interferon gamma (IFN-γ) gene therapy after surgery. Dogs with newly diagnosed glioma underwent surgical tumor debulking and were randomized to receive 1) autologous tumor lysate vaccines with CpG ODN as an adjuvant (n = 12) or 2) Ad-mediated interferon gamma (IFN-γ) gene therapy injected around the resection cavity followed by vaccine immunotherapy (n = 12). A grade IV IFN-γ dose-related toxicity (severe encephalitis and lymphocytic perivascular cuffing) resulted in death of one dog. No further adverse events were seen at a lower IFN-γ dose supporting the safety of the treatment. This immunotherapy activated a humoral response with specific tumor-reactive IgG antibodies detected after vaccination in all dogs. Addition of IFN-γ gene therapy did not affect the median overall survival time of 204 days versus 211 days with vaccine alone. As expected, there were significant differences (P = 0.036) in survival between dogs with low-grade (369 days) versus high-grade (204 days) tumors. During postmortem analysis, no dog with a low-grade tumor had recurrence, whereas all dogs with grade III/IV tumors died from progression. We hoped that forced IFN-γ expression would sensitize residual tumor cells to CTL recognition and recruit NK cells to kill MHC Ilow/- cells, thereby enhancing the effects of vaccine immunotherapy. Our data failed to support this theory, however the lack of difference could be due to the small number of dogs in each group (type II error) or to insufficient in situ expression of IFN-γ to elicit the desired effect.

Gadolinium enhancement patterns of tumefactive demyelinating lesions: correlations with brain biopsy findings and pathophysiology.

Tumefactive demyelinating lesions (TDLs) can mimic brain tumors on radiological images. TDLs are often referred to as tumefactive multiple sclerosis (TMS), but the heterogeneous nature and monophasic course of TDLs do not fulfill clinical and magnetic resonance imaging (MRI) criteria for multiple sclerosis. Redefining TDLs, TMS and other inflammatory brain lesions is essential for the accurate clinical diagnosis of extensive demyelinating brain lesions. We retrospectively analyzed MRI from nine TDL cases that underwent brain biopsy. Patterns of gadolinium enhancement on MRI were categorized as homogenous, inhomogeneous, patchy and diffuse, open ring or irregular rim, and were compared with pathological hallmarks including demyelination, central necrosis, macrophage infiltration, angiogenesis and perivascular lymphocytic cuffing. All cases had coexistence of demyelinating features and axonal loss. Open-ring and irregular rim patterns of gadolinium enhancement were associated with macrophage infiltrations and angiogenesis at the inflammatory border. An inhomogeneous pattern of gadolinium enhancement was associated with perivascular lymphocytic cuffing. Central necrosis was seen in cases of severe multiple sclerosis and hemorrhagic leukoencephalopathy. These results suggest that the radiological features of TDLs may be related to different pathological processes, and indicate that MRI may be useful in understanding their pathophysiology. Further investigation is needed to determine the precise disease entity of these inflammatory demyelinating brain lesions.

Pseudotumor formation following large-diameter metal-on-metal total hip arthroplasty—Report of two cases and literature review

Pseudotumor after metal-on-metal total hip arthroplasty is an increasingly frequent complication in Taiwan. Orthopedic surgeons should be aware of this complication and follow up their patients regularly so that the disease can be detected early and properly managed. We report two cases of this complication. Case 1 exhibited cystic change with fluid accumulation, and in Case 2 a semisolid mass was found. In Case 1, a high inclination angle of the cup (at 65°) was noted. In Case 2, the cup was placed at a normal inclination angle, but it was too anteverted (31°). The histopathological studies revealed that the cystic pseudotumor had more diffuse lymphocyte infiltration and perivascular lymphocyte cuffing with eosinophil and plasma cells. The semisolid mass of Case 2 had less lymphocyte infiltration. Both cases had metal debris with foreign body granuloma. In patients with residual groin pain and a palpable mass after surgery, the possibility of pseudotumor formation should be considered. Various imaging techniques, such as ultrasound, computed tomography scan, and magnetic resonance imaging, can be used to confirm the presence of such lesions. Revision with nonmetal-on-metal articulation is suggested to relieve the symptoms.

Atypical cerebral listeriosis associated with Listeria innocua in a beef bull

Natural infections of cattle associated with Listeria innocua have not been reported. This report describes the first case of cerebral listeriosis in a bull due to Listeria innocua. The animal presented neurological signs characterized by weakness, incoordination and recumbency. Histopathologic evaluation of brain tissue revealed multifocal microabscesses, perivascular lymphocytic cuffing, vasculitis, oedema and haemorrhages. All lesions extended from the medulla oblongata to the basal nuclei/parietal cortex area. Indirect immunohistochemistry labelled for Listeria sp. in the brain tissue, but not for Listeria monocytogenes, neurotropic Flaviviruses, BVDV, bovine Herpesvirus 1, Chlamydophila spp. and Histophilus somni. PCR was negative for ovine herpesvirus. L. innocua was isolated from brainstem and identified by biochemical tests (Camp and beta-hemolysis negative). Subsequently, the species was confirmed by a duplex PCR and minisequencing assays. L. innocua should be histologically considered as a differential diagnosis of thrombotic meningoencephalitis, malignant catarrhal fever and cerebral listeriosis due to L. monocytogenes in cattle.

Cerebrospinal nematodiasis outbreak in an urban outdoor aviary of cockatiels (Nymphicus hollandicus) in southern California

An outbreak of cerebrospinal nematodiasis due to Baylisascaris sp. was documented in an urban outdoor aviary in southern California. Thirty-four out of 35 cockatiels (Nymphicus hollandicus, 97%) showed a variety of neurological signs including ataxia, lateral recumbency, opisthotonus, and torticollis. Thirteen carcasses were submitted for necropsy; the histological lesions were restricted to the central nervous system (brain and spinal cord) and were predominantly degenerative, characterized by multifocal white matter vacuolation, gliosis, axonal swelling, gitter cell infiltration, and mild hemorrhage, rarely accompanied by mild granulomatous inflammation and mild lymphocytic perivascular cuffs. Nematode larvae morphologically compatible with Baylisascaris sp. were observed in the brain of 5 birds, away from the lesion site.

Surto de intoxicação por sal em suínos em Santa Catarina

Descreve-se a ocorrência de surto de intoxicação por sal em suínos de duas propriedades, onde 70 porcos morreram. Soro de leite proveniente da salga de queijo era servido no cocho como única fonte hídrica aos animais. Não havia bebedouros nas instalações. Um dia após o fornecimento do soro, os porcos começaram a adoecer e apresentaram salivação excessiva, movimentos de pedalagem, opistótono e tremores cíclicos. Na necropsia, dois suínos apresentaram achatamento das circunvoluções do córtex telencefálico e um outro, edema no córtex telencefálico. Na histopatologia, observou-se necrose neuronal laminar difusa acentuada no córtex telencefálico, astrócitos de Alzheimer tipo II (AIIA), infiltrado multifocal perivascular de eosinófilos e linfócitos e edema perivascular. Outros achados incluíram marcação imuno-histoquímica fraca ou ausente para proteína glial fibrilar ácida (GFAP), mas intensa marcação positiva no citoplasma dos AIIA para S-100. As concentrações de sódio sérico e do líquor mensuradas nos porcos estudados foram de 140 e 156mmol/L, respectivamente.

Lymphoid Hyperplasia and Eosinophilic Pneumonia as Histologic Manifestations of Amiodarone-induced Lung Toxicity

Amiodarone use is often limited by pulmonary toxicity. Amiodarone lung disease (ALD) classically manifests as organizing pneumonia with intra-alveolar foamy macrophages, but other patterns may also occur. Here we report 2 previously unreported patterns of ALD: lymphoid hyperplasia (LH) and eosinophilic pneumonia (EP). We identified patients with LH or EP as a prominent feature among 75 cases of probable ALD from the authors' teaching files collected from 1997 to 2010. Clinical history and lung wedge biopsies were reviewed. Twelve patients (7 men) met inclusion criteria (median age, 71 y). The exact amiodarone dose was known in all cases (median, 200 mg/d). Treatment duration was known in 10 cases and ranged from 1 to 12 years. Thoracic imaging showed diffuse infiltrates causing concern for a diagnosis of ALD. Histologic review revealed intra-alveolar foamy macrophages in all cases. Eight cases prominently displayed patterns of LH, including diffuse LH (7), follicular bronchiolitis (5), lymphoid interstitial pneumonia (2), and lymphocytic perivascular cuffing (2). Two showed features of acute EP, including diffuse alveolar damage with abundant eosinophils. Two showed features of chronic EP, including interstitial pneumonia with abundant eosinophils, patchy organization, and fibrinous exudates with macrophages and eosinophils. One chronic EP case also showed focal LH. Additional features included intra-alveolar giant cells (6), pleuritis (3), small poorly formed granulomas (3), and thrombi (2). LH and EP are previously unrecognized histopathologic manifestations of ALD, and amiodarone exposure should be included in their differential diagnosis.

Adverse reactions to metal debris: histopathological features of periprosthetic soft tissue reactions seen in association with failed metal on metal hip arthroplasties

AimTo describe the histopathology of localised adverse reactions to metal debris (ARMD) seen in association with failed metal on metal (MoM) hip arthroplasties. The nature of aseptic lymphocytic vasculitis associated...

Susac syndrome: a neuropathological description of an underdiagnosed entity

Susac syndrome is an under-recognised disease characterised by the clinical triad of encephalopathy, retinal artery occlusion and sensorineural hearing loss. It is thought to be due to a microangio-pathy of uncertain aetiology. Only limited histopathological descriptions are available. We aimed to better characterise the neuropathological features of Susac syndrome and to define the vascular pathology present. Neurosurgical biopsies from three cases of Susac syndrome were examined morphologically, histo-chemically and immunohistochemically. Controls included cerebral and cerebellar tissue from six age matched cases. In addition, patient serum was assessed in a direct immunofluores-cence assay. All three cases had cortical microinfarcts of varying ages. Acute cases showed perivascular CD8 positive lymphocytic cuffs with endothelial swelling and subtle micro-infarcts. Older cases showed thick walled, non-congophilic, hyalinised blood vessels. Intravascular fibrin thrombi, disrupted elastic lamina or complement activation was not seen. Serology testing revealed IgG binding to the internal elastic lamina in one case, a non-specific finding. We conclude that the neuropathology of Susac syndrome is relatively non-specific, and that vascular damage is T-cell-mediated rather than due to humoral responses. Awareness of the clinical, radiological and neuropathological features will aid the pathologist in alerting clinicians to the possibility of this treatable disorder.