Zika Virus Associated with Microcephaly Mlakar, Jernej; Korva, Misa; Tul, Nataša ...
New England journal of medicine/The New England journal of medicine,
2016-Mar-10, Letnik:
374, Številka:
10
Journal Article
Recenzirano
Odprti dostop
A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased ...incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.
-The 2015 outbreak of Zika virus in Brazil resulted in a 20-times increased prevalence of congenital microcephaly in stillborns and neonates and was instrumental in raising the suspicion of a causal ...association between Zika virus and microcephaly.
-To provide a comprehensive description of the neuropathologic features of congenital Zika virus infection.
-Autopsy evaluation of the brain from a fetus of 32 weeks and 6 days of gestation, with a prenatal diagnosis of microcephaly associated with polymerase chain reaction-confirmed, fetal, Zika virus infection.
-Multiple severe pathology findings were present. These included lissencephaly, except for the occipital lobes, where some pachygyria was observed. Also present was reduction and thinning of white matter, ventriculomegaly of the lateral ventricles, and coalescent calcifications in the cortical-subcortical white matter border associated with glioneuronal outbursting into the subarachnoid space above and heterotopias below. There were small, scattered calcifications in the basal ganglia, with fewer in the white matter and germinal matrix, and none in the cerebellum and brainstem. The cerebellum and pontine base were atrophic because of Wallerian degeneration or maldevelopment of descending tracts and pontocerebellar connections.
-Our findings are in agreement with neuroimaging of Zika virus-associated fetal and infant micrencephalic brains and, to some extent, with neuroimaging of other intrauterine infections causing microcephaly.
Whereas the pigmented (melanotic) variant of diffuse neurofibroma (DNF) with positivity for melanocytic markers is well recognized, expression of melanocytic markers in nonpigmented DNF has not been ...systematically studied. We analyzed 28 unselected consecutive DNFs for expression of melanocytic markers, including melan A, microphthalmia transcription factor (MITF), and HMB-45 antigen. For comparison, we also analyzed 40 localized skin neurofibromas and 7 intraneural neurofibromas. One case of nonpigmented DNF was analyzed by electron microscopy. Of the 28 DNFs studied by immunohistochemistry, 3 were pigmented and 25 nonpigmented. The 3 pigmented DNFs and 9 of 25 (36%) nonpigmented DNFs expressed melan A, MITF, and HMB-45 antigen. These markers were expressed either focally or more diffusely, typically in a minority of the lesional cells, and usually both in the dermal and subcutaneous portion of the DNF. Melan A was expressed in the largest number of the lesional cells (up to 50%), whereas only a small fraction of the melan A-positive cells (from 5% to 10% in most cases) also expressed HMB-45 antigen. None of the 47 non-DNFs expressed these markers. Ultrastructurally, melanosomes were present in some cells in nonpigmented DNF that expressed the melanocytic markers. Twenty-three of 28 (82%) DNFs, including 10 of 12 (83%) DNFs with melanocytic differentiation, were associated with neurofibromatosis type 1. Expression of melanocytic markers, including melan A, HMB-45 antigen, and MITF in DNF is a potential pitfall in differential diagnosis with melanocytic lesions that may clinically or histopathologically resemble DNF, in particular congenital melanocytic nevus with neurotization and neurofibroma-like melanoma.
Understanding the role of alternative complement pathway dysregulation in membranoproliferative glomerulonephritis (MPGN) has led to a dramatic shift in its classification into two subgroups: immune ...complex-mediated MPGN and complement-mediated MPGN, consisting of dense deposit disease and C3 glomerulonephritis (C3GN). A limited number of C3GN cases have been published to date with not yet conclusive results since the novel therapeutic approach with eculizumab was introduced.
We report the clinical follow-up of a 16-year-old patient in whom a diagnosis of C3GN was confirmed by immunofluorescence and electron microscopy in second and third kidney biopsies, while the first biopsy revealed idiopathic immune complex-mediated MPGN type III, Anders and Strife variant, which failed to improve after several attempts at conventional immunosuppression therapy. Although applied late in an already fairly advanced stage of the severe active form of MPGN, the efficacy of eculizumab on C3GN was evidenced clinically and pathohistologically. Its beneficial influence on pathomorphogenesis was demonstrated by a unique follow-up in the last three biopsies, despite the recent observation, confirmed in this study, of eculizumab binding within the kidney tissue.
Clinicians and pathologists should be aware that, in some patients, an underlying genetic or acquired complement alternative pathway abnormality can be masked by an initial immune complex-mediated mechanism, which subsequently triggers an unbalanced excessive continual driving of complement terminal pathway activation and the development of C3GN. In such a patient, supplementary steroids in addition to eculizumab appear necessary to achieve an adequate response.
There are only a few reports of the co-occurrence of acute poststreptococcal glomerulonephritis (APGN) and acute rheumatic fever. We report an unusual case of a 3-year-old boy with nephrotic syndrome ...and acute renal failure with the transitional need for peritoneal dialysis, biopsy-proven atypical IgA-dominant APGN, and concomitant acute rheumatic fever, successfully treated by steroids. Aggressive treatment with pulses of methylprednisolone proved to be successful and we recommend its use in this type of cases.
Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare immune-complex small vessel systemic vasculitis involving kidney in about 50% of patients. Characteristic clinical features are ...recurrent urticaria, decreased serum complement, skin vasculitis, arthritis, eye inflammation, abdominal pain, glomerulonephritis and positive anti-C1q antibodies. We report a 36-year-old woman with a 12-year history of recurrent urticaria and 2 years of urticarial vasculitis. On admission, she also had arthritis, pleuritis and pericarditis, abdominal pain, pathologic urinalysis, low serum values of C3, C4 and CH50. All immunoserology was negative except for ANA 1:80 and anti-C1q 620 IU. ’Full-house’ immune complex vasculitis was demonstrated in skin and lung biopsies. A kidney biopsy showed diffuse proliferative segmental active and sclerosing glomerulonephritis with mesangial and endocapillary proliferation, neutrophil exudation, necrosis, extracapillary crescents and segmental and global glomerulosclerosis. ’Full-house’ glomerular and extensive extraglomerular vascular and tubulointerstitial immune deposits with dominant IgG, C3 and C1q were noted by immunofluorescence. Electron microscopy revealed electron dense deposits with an ultrastructural ’fingerprint’ pattern in the glomerular mesangium, transmembranous in capillary walls and in the arteriolar wall. Our patient fulfilled the criteria for HUVS and SLE, in accordance with the not infrequent clinical and immunoserological overlapping of the two diseases.
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