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Inflammation and atherosclerosis. Atherosclerotic lesions in Takayasu arteritis.

Takayasu arteritis is a chronic vasculitis, mainly involving the aorta and its main branches as well as the coronary and pulmonary arteries, causing stenosis and/or obstruction due to thrombus formation or dilatation due to aneurysmal formation and/or rupture of the involved arteries. These characteristic anomalies resulted from ischemia of retinal arteries due to the obstruction of cervical vessels. In Western countries this disease is also known as "pulseless disease," because the pulse is frequently absent due to the obstruction of subclavian or branchial arteries. The pathogenesis of this morbid condition is still unknown. Epidemiologically, it is found mostly in female patients and is more prevalent in Asian and Latin American countries. Affected areas consist of a mixture of both active, productive inflammatory lesions, and old fibrous lesions. Autoimmune processes stimulated by viral infection and other unknown causative factors may play an important role under these pathophysiological conditions because HLA analysis revealed a statistically significant high frequency of haplotype A24-B52-DR2 in these patients in Japan. Documentation of atherosclerotic complications in young female patients with Takayasu arteritis who are generally free from traditional atherosclerosis risk factors may be clinical evidence that inflammation is indeed an important risk factor in atherogenesis.

Arteries↗

Mycoplasma-like organism induced murine cardiac microvasculopathy. A transmission electron microscopic study.

Mycoplasma-Like Organisms [MLO] are intracellular cell wall deficient bacteria that cause ocular chronic vasculitis in man and chronic vascular disease in plants. Since MLO do not grow in culture, diagnosis of MLO-induced disease requires identification of the organisms by electron microscopy. Ultrastructurally, MLO appear as pleomorphic tubulo-spherical and filamentous organisms. In human ocular disease MLO have been detected in parasitised leucocytes and retinal pigment epithelial cells. We have previously reported the results of injecting MLO infected human vitreous into mouse eyelids. Two thirds of the mice developed chronic disease at the inoculation site, but, more importantly, the mice also developed lethal systemic MLO disease. Carditis with histologic features similar to those of various types of human carditis occurred in 18% of the mice. This report describes the ultrastructural features of the cardiac microvascular MLO disease in those 18 mice that died of carditis after inoculation with human MLO-infected vitreous. MLO were identified in leucocytes and endothelial cells of the murine vascular lesions. The vascular lesions were characterized by destruction of vessel walls as well as proliferation of endothelial cells. Electron dense deposits were seen in basement membranes and pericytial tissues. Similar features have been described in other bacterial vascular infections and in human idiopathic carditis. We suggest that MLO could be a cause of human cardiovascular disease and should be looked for in such cases.

Animals↗

The ultrastructural pathology of congenital murine toxoplasmic retinochoroiditis. Part II: The morphology of the inflammatory changes.

A congenital murine model of toxoplasmic retinochoroiditis was employed to study the ultrastructural pathology of retinal parasitization by Toxoplasma gondii. Forty-two eyes from infected mice (18-22-weeks-old) and 24 eyes from control animals were studied by light microscopy (semithin sections). Twenty-six of the eyes from infected animals and six from the control group were subsequently selected for transmission electron microscopy. Control tissues showed no significant abnormality. The pathological changes in diseased tissues ranged in severity from low-grade mononuclear cell infiltration in the subretinal space to complete destruction of the outer retina, the retinal pigment epithelium and the choroid in the presence of a granulomatous inflammatory reaction. Phagocytosis of photoreceptor outer segments by macrophages was observed. Both macrophages and lymphocytes appeared to mediate photoreceptor lysis in eyes which were moderately affected by the disease. Severely affected eyes exhibited vasculitis and inflammatory cell invasion into the vitreous. A lymphoplasmacytoid cell infiltrate was present in the outer retina and choroid in these eyes. There was no evidence that Toxoplasma cysts provided foci for inflammatory cell attack.

Animals↗

Acute posterior multifocal placoid pigment epitheliopathy and late-onset meningo-encephalitis.

A steroid-sensitive meningo-encephalopathy developed in a healthy young woman 5 1/2 years after the occurrence of acute posterior multifocal placoid pigment epitheliopathy (APMPPE). The association of APMPPE with systemic and neurologic inflammatory disorders has been well documented, but to the knowledge of the authors, this is the first report of an APMPPE patient in which there was delayed onset of the meningo-encephalopathy. The association with dermal vasculitis, nephropathy, meningo-encephalitis, cerebral vasculitis, and thyroiditis suggests that APMPPE may be one manifestation of a diffuse systemic inflammatory condition.

Adult↗

Susac syndrome.

OBJECTIVE: The objective of this study was to describe the clinical manifestations; radiographic, audiometric, and retinal fluorescein angiography findings; pathogenesis and treatment of Susac syndrome with review of the literature. STUDY DESIGN: We conducted a retrospective case review. SETTING: This study was conducted at a tertiary referral center. PATIENT: A 50-year-old woman presented with recurrent episodes of neurologic symptoms, bilateral sensorineural hearing loss, and silent retinal artery occlusion. INTERVENTIONS: The patient underwent complete evaluation, including magnetic resonance image studies, audiometric tests, and retinal fluorescein angiography. She was treated initially with corticosteroids and later with other immunosuppressive agents. RESULTS: The patient was initially diagnosed with left sudden sensorineural hearing loss. Despite comprehensive clinical and laboratory studies that did not reveal systemic disease, 3 weeks later, the patient developed vertigo, sensorineural hearing loss, and tinnitus in the opposite ear. The neurologic involvement and the bilateral audiologic manifestations raised the possibility of Susac syndrome. CONCLUSION: Susac syndrome is a rare disorder of unknown origin characterized by the triad of encephalopathy, fluctuating hearing loss, and visual loss resulting from microangiopathy of the brain, cochlea, and retina. The multiple organ involvement seen in Susac syndrome raises a differential diagnosis ranging from autoimmune disease, through systemic vasculitis, to multiple sclerosis. Otolaryngologists should be aware of this syndrome as a result of the vestibulocochlear manifestations and the multidisciplinary evaluation that is required.

Audiometry, Pure-Tone↗

Electroretinography and electro-oculography to localize abnormalities in early-stage inflammatory eye disease.

Electrophysiological investigations were performed in patients with inflammatory eye disease characterized by the presence of vitreous cells. The eyes were classified into four categories on the basis of fluorescein angiography: 1) no fluorescein leakage from retinal vessels, 2) fluorescein leakage from peripheral retinal vessels, 3) fluorescein leakage from the disc or macular vessels, and 4) fluorescein leakage from retinal vessels associated with pigment epithelial and choroidal changes. The electro-oculogram light rise was abnormally increased in the eyes in category 1, but it progressively declined for those in the other categories. The ratio of the b-wave (postreceptoral component) and a-wave (receptoral component) of the flash electroretinogram was unchanged in all categories, but the electroretinographic amplitudes progressively declined from a somewhat supernormal level in category 1 to subnormal in the other categories. Thus, in inflammatory eye disease, changes in the electrical potentials arising in the pigment epithelium and photoreceptors are the earliest detectable signs. Some biochemical changes in the choroid, pigment epithelium, and the photoreceptors appear to take place before any pathological changes in these structures or in the retinal vessels are detectable by ophthalmoscopy or fluorescein angiography.

Adult↗

Neurological manifestations of polyarteritis nodosa associated with the antiphospholipid syndrome.

The association between antiphospholipid syndrome (APS) and vasculitis is rare and continues to evoke great interest. We report a case with neurological manifestations of polyarteritis nodosa (PAN) and concurrent APS. Electromyography and neuromuscular biopsy of the limb showed an axonal polyneuropathy following obliteration and necrosis of medium sized arteries, initially suggesting PAN. This vasculitis was confirmed on visceral selective arteriography, with the presence of numerous aneurysms. Cerebral MRI revealed multiple cortical and subcortical signals in the fronto-parietal areas, corresponding to ischemic microvascular lesions of APS. This association was confirmed by the presence IgG anticardiolipid, the past medical history of skin necrotic lesions and central retinal obliteration. Pulse intravenous cyclophosphamide, oral prednisolone and curative anticoagulation led to stabilization for 8 months.

Adult↗

Localized cutaneous necrosis associated with the antiphospholipid syndrome.

A 34-year-old woman with systemic lupus erythematosus and high titres of antiphospholipid antibodies was admitted to hospital suffering a viral illness but developed haemorrhagic and necrotic areas on the neck and anterior chest 7 days following cessation of warfarin. Anticoagulation had been initiated following a retinal vein thrombosis, but was ceased on day 4 of admission when she was found to be excessively anticoagulated (international normalized ratio (INR) > 10). However, at the time of developing the cutaneous lesions, the INR was sub-therapeutic. Histology of a skin biopsy from the neck revealed thrombosis of upper dermal blood vessels without vasculitis, consistent with antiphospholipid antibody-related skin necrosis. This case illustrates one of the cutaneous features that can occur in patients with elevated titres of antiphospholipid antibodies and the importance of closely monitoring anticoagulation in such patients.

Adult↗

Systemic cholesterol microembolization syndrome masquerading as giant cell arteritis.

Two patients with clinical features consistent with giant cell arteritis were found to have systemic cholesterol microembolization syndromes. Diagnostic confirmation was established by a muscle biopsy in one patient and by a kidney biopsy in the other. Systemic cholesterol embolization can masquerade as a variety of disorders, including vasculitis, and should be considered in a patient with suspected giant cell arteritis who has a negative temporal artery biopsy.

Aged↗

Neurological manifestations of acute posterior multifocal placoid pigment epitheliopathy.

BACKGROUND: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a chorioretinal disease that causes acute visual symptoms with characteristic fundus findings. Although this entity has been associated with a variety of neurological complications, it has received little attention in the neurological literature. We wanted to emphasize the spectrum of neurological involvement, in particular the occurrence and management of strokes in patients with APMPPE. CASE DESCRIPTIONS: We report three patients with APMPPE and neurological disease. All three presented with marked visual disturbances and headaches. One patient developed recurrent strokes involving different vascular territories of the brain and required immunosuppressive treatment for presumed cerebral vasculitis. The other two patients had cerebrospinal fluid pleocytosis and persistent headaches but recovered spontaneously. The review of the literature demonstrates a particular pattern of neurological complications in a subgroup of patients with APMPPE. CONCLUSIONS: APMPPE should be considered among the causes of stroke and aseptic meningitis in young adults. The diagnosis is critically dependent on a thorough ophthalmologic examination. Severe neurological complications are difficult to predict at the onset of the ophthalmologic disease. The patients should be monitored closely. If investigations suggest cerebral vasculitis, immunosuppressive treatment may be helpful to prevent recurrences.

Acute Disease↗

Central serous retinopathy associated with Weber-Christian disease.

PURPOSE: To report an association between central serous retinopathy and Weber-Christian disease. METHODS: A case report. RESULTS: Central serous retinopathy was noticed in a patient with Weber-Christian disease possibly secondary to vasculitis involving the choriocapillaris. CONCLUSIONS: Central serous retinopathy may be associated with an uncommon systemic condition like Weber-Christian disease.

Exudates and Transudates↗

[Peripheral neurologic manifestations of infection by the human immunodeficiency virus].

Peripheral nerve lesions observed in the progressive immunodeficiency associated with infection are remarkable for their diversity and their potential severity. At the onset, demyelinating neuropathies predominate, often with signs of atypical polyradiculoneuritis associated with inflammatory lesions or vasculitis sometimes of the necrotizing type, as that observed in periarteritis nodosa. Later on, at the immunosuppression stage, axonal lesions predominate. At the AIDS stage one may find lymphomatous infiltration of nerves and nerve roots and, chiefly, opportunistic cytomegalovirus (CMV) infection. This infection produces meningoradiculitis, mainly in the territory of the cauda equina, or multifocal neuropathy frequently associated with CMV retinitis. Early treatment of CMV neuropathies may stabilize the lesions or even result in functional improvement, but the overall prognosis of late neuropathies remains poor.

Cell Division↗

Efficacy and safety of rituximab in type II mixed cryoglobulinemia.

The best treatment of type II mixed cryoglobulinemia (MC) has still to be defined. Antiviral treatment for the frequent underlying infectious trigger hepatitis C virus (HCV) may be ineffective, contraindicated, or not tolerated in a fraction of cases, whereas current immunosuppressive treatments may lead to relevant complications. Selective B-cell blockade with rituximab was used in this study, based on favorable results in preliminary experience. Fifteen consecutive patients with type II MC (HCV-related in 12 of 15) were treated with rituximab, 375 mg/m(2) intravenously weekly for 4 weeks. Only medium- to low-dose steroids were allowed, if already administered at the time of recruitment. All patients had active disease, poorly controlled or difficult to manage with previous treatments, including corticosteroids in all. Efficacy and safety of rituximab therapy were evaluated in the following 6 months. The overall follow-up after rituximab treatment ranged from 9 to 31 months. Rituximab proved effective on skin vasculitis manifestations (ulcers, purpura, or urticaria), subjective symptoms of peripheral neuropathy, low-grade B-cell lymphoma, arthralgias, and fever. Nephritis of recent onset went into remission in one case. Laboratory features, that is, significantly decreased serum rheumatoid factor and cryoglobulins and increased C4, were consistent with the clinical efficacy. Treatment was well tolerated, with no infectious complications. Thrombosis of retinal artery or self-limiting panniculitis occurred in one patient each. Rituximab may represent a safe and effective alternative to standard immunosuppression in type II MC. Controlled studies are needed to better define drug indications and the cost-efficacy profile in the different systemic manifestations.

Adrenal Cortex Hormones↗

[Myxoma of the left atrium with neurologic manifestations: 8 cases].

A cohort of 8 patients with myxoma of the left atria and neurological manifestations is reported. Cerebral ischaemia, sometimes responsible for epileptic seizures, led to the discover of the myxoma (5 cases) or recurrence after exeresis (1 case) with imaging evidence of cerebral infarction in 5 cases. The first manifestation was a retinal embolism and temporary ischaemia in 1 case and pulmonary embolism with regressive cerebral ischaemia in another case with bilateral myxoma. Some clinical particularities should be underlined including exercise-induced neurological defect (3 cases), systemic embolism associated with cerebral infarction (3 cases), migraine headache as the initial manifestation (1 case) preceding by a pseudolupic syndrome suggesting the possibility of cerebral vasculitis or infectious endocarditis (1 case). The prognosis depends on the risk of recurrent atrial tumour formation (1 case). Metastases are rare. Multiple cerebral aneurysms (3 cases) did not lead to haemorrhagic complications.

Adult↗

Acute posterior multifocal placoid pigment epitheliopathy associated with cerebral vasculitis and homonymous hemianopia.

An 18-year-old man developed acute posterior multifocal placoid pigment epitheliopathy and homonymous hemianopia. Cerebral angiography showed cerebral vasculitis probably with occipital infarction. To the best of our knowledge, this is the first reported case with such concomitant visual defects. Other published reports suggest that such cerebral vasculitis may not be unusual in acute posterior multifocal placoid pigment epitheliopathy.

Acute Disease↗

[Antiphospholipid antibodies and occlusive vascular disease].

The antiphospholipid syndrome is characterized by venous and/or arterial thrombosis, recurrent foetal loss, thrombocytopenia and the presence of antiphospholipid antibodies. This study presents three case reports, which emphasize the multiform clinical features of the syndrome: one case of uncomplicated myocardial infarction in childhood and two prolonged, clinically elusive case histories, both with fatal outcome due to acute, multifocal, non-inflammatory vascular occlusion. It is important to distinguish between this syndrome and various vasculitis syndromes, although consensus on therapy for the antiphospholipid syndrome has not yet been achieved.

Adolescent↗

Malignant catarrhal fever in bison, acute and chronic cases.

Acute malignant catarrhal fever (MCF) was diagnosed in 10 bison from 6 herds and ranging from 1 to 6 years of age. The pattern of clinical signs and morphologic lesions differed among bison. Combinations of corneal opacity, lacrimation, nasal discharge, depression, excess salivation, anorexia, diarrhea, melena, and hematuria were observed. Vasculitis characterized by lymphoid infiltrates in the adventia with variable extension into media and intima was found in multiple tissues in each animal. Fibrinoid vascular necrosis was rare. Ulceration in the alimentary tract was found in 9/10 bison, and ulceration or hemorrhage in the urinary bladder was found in 8/10 bison. Lymphoid infiltrates were present in 7 of 9 livers and 9 of 9 kidneys examined histologically. Hyperplasia of lymph nodes was observed in 5 bison. Chronic MCF was diagnosed in 1 bison with an 80-day course of illness that began with lacrimation, corneal opacity, mucoid nasal discharge, depression, and anorexia. These signs ceased after 15 days but circling and blindness developed on day 76. Chronic vascular lesions characterized by endothelial cell hypertrophy, intimal thickening, fragmentation of the internal elastic membrane, smooth muscle hypertrophy, and adventitial infiltrates of lymphocytes and plasma cells were found in many organs. The retinal arteries had chronic inflammation and acute transmural fibrinoid necrosis. The retinas were infarcted. Polymerase chain reaction technique for amplification of ovine herpesvirus 2 sequences was performed on formalin-fixed tissues, and viral sequences were detected in 1-7 tissues from each animal. These viral sequences were not found in tissues of 4 bison not affected by MCF.

Acute Disease↗

Radiation choroidal vasculopathy: an indocyanine green angiography study.

An indocyanine green angiography (ICG-A) study of choroidal vasculature in the irradiated peritumoral zone in 16 eyes treated with 106Ru/106Rh brachytherapy for choroidal melanoma was performed between 4 and 72 months following treatment. The earliest changes observed were peritumoral atrophy of the retinal pigment epithelium and choriocapillaries. With time, the larger choroidal vessels progressively became non-perfused. There was only minimal staining of the smaller vessels. However, at 2 years or more after radiotherapy the larger choroidal vessels showed progressive vascular wall staining with ICG ('perivasculitis') associated with continuing closure. Previous histopathological studies of radiation damage to the choroid have demonstrated atrophy and occlusion of the vasculature but have shown no evidence of vasculitis. It is suggested that ICG staining of the choroidal vascular wall in radiation choroidopathy is due to radiation-induced endothelial cell loss or dysfunction rather than a true vasculitis. Subsequent progression results in vascular occlusion, and development of new clusters of abnormal choroidal vessels.

Angiography↗