Context.-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.Objective.-To provide a comprehensive description of the neuropathologic features of congenital Zika virus infection.Design.-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.Results.-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.Conclusion.-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.

(2018) Neuropathology and Applied Neurobiology 44, 550-562 Familial tauopathy with P364S MAPT mutation: clinical course, neuropathology and ultrastructure of neuronal tau inclusions Aims: This report presents the clinical course, neuropathology and ultrastructure of neuronal tau inclusions of four Slovene relatives with P364S MAPT mutation. Methods: The clinical history of three out of four P364S MAPT mutation carriers was taken. After formalin fixation, thorough sampling of the central nervous system was followed by paraffin embedding, H&E, Gallyas, Bielschowsky and immunostaining with AT8, anti-3R, anti-4R tau, anti-amyloid-b, anti-TDP43 and anti-alpha-synuclein antibodies. The distribution and density of different types of neuronal tau inclusions were semiquantitatively assessed. In addition, the ultrastructure of neuronal tau inclusions was analysed. Results: Macroscopic examination of the brains was unremarkable. Microscopically, neuronal tau inclusions of almost all known types were widespread and distributed fairly uniformly in all cases.Pick bodies and swollen neurones were found in only one family member. Mutant tau was composed of 3R and 4R isoforms, with a slight predominance of 3R tau. Composite neuronal tau inclusion (CNTI), found in all four relatives, was a hallmark of the P364S MAPT mutation. CNTI showed compartmental differences in H&E and Gallyas staining, tau isoforms immunolabelling and ultrastructure, displaying fuzzy fibrils in the core and paired twisted tubules at the periphery. Conclusions: P364S MAPT mutation is characterized clinically by a variable combination of frontotemporal dementia, parkinsonism and motor neurone disease of short duration, and neuropathologically by a widespread uniform distribution of all known neuronal tau inclusions in one family member. Two-compartment CNTI is a unique characteristic of the P364S MAPT mutation.

virus associated microcephaly/micrencephaly-fetal brain imaging in comparison with neuropathology. BJOG 2017;124:521-525. In December 2015, during the Zika virus (ZIKV) epidemic in Brazil, a possible association between ZIKV infection during pregnancy and fetal brain malformations was suspected due to a 20-fold rise in cases of microcephaly among newborns. 1,2 Several reports published thereafter have strengthened the association between ZIKV and fetal brain damage. [3][4][5][6] Prenatal diagnosis of microcephaly and/or fetal brain damage caused by infectious agents is based on neuroimaging techniques, ultrasound and magnetic resonance imaging (MRI), which in combination display most pathological changes, such as microcephaly (small head), micrencephaly (small brain), ventriculomegaly, cortical maldevelopment, porencephalic cysts, cerebellar atrophy and calcifications. 7,8 In this case report we compare intrauterine fetal brain neuroimaging with post-mortem neuropathology in a confirmed case of microcephaly/micrencephaly associated with ZIKV, giving a possible explanation for some imaging findings that were not confirmed on autopsy.A 25-year-old European woman who lived in Natal, Bahia, Brazil developed signs of infection during the 13th week of gestation and ZIKV was highly suspected. Ultrasound at 14th and 20th weeks of gestation showed normal fetal growth and anatomy. 5 After returning to Europe in the late second trimester of her pregnancy, ultrasound showed fetal brain anomalies for the first time. She was referred to a tertiary referral hospital where ultrasound and MRI were performed in the 29th week of gestation, and ultrasound was repeated in the 31st and 32nd weeks of gestation.The ultrasound examinations revealed microcephaly, ventriculomegaly, enlarged cisterna magna, small cerebellum and scattered calcifications throughout the brain (Figure 1A, see Figure S1).On MRI ( Figure 1B-D), a severe reduction of the brain volume was observed, predominantly of the frontal and parieto-occipital lobes. The volume of the temporal lobes was relatively spared. Infratentorial structures were less severely affected although transverse cerebellar diameter and vermis height were smaller than expected for gestational age. The basal ganglia, thalami and brainstem were relatively spared. A large area of cystic encephalomalacia was demonstrated in the right parieto-occipital lobe, and smaller pseudocysts were visible in the left occipital lobe and in the frontal subcortical white matter. Confluent T2 hyperintensities of the supratentorial white matter with increased diffusion on diffusion-weighted imaging were noticed in the temporo-occipital lobes, corresponding to oedema. On T2 fast field echo (FFE) sequence, subtle hypointensity in the left caudothalamic groove was noted, probably corresponding to a small haemorrhage. Several small T2 hypointense foci in the periventricular and cortical-subcortical areas could correspond to grey matter displacement or calcifications ( Figure 1D), the latter being well depicted 521 ª ...