Central nervous system involvement in two siblings affected by hereditary transthyretin amyloidosis 30 years after liver transplantation: a model for gene-silencing therapies.

Hereditary transthyretin amyloidosis (ATTRv) is a genetic, autosomal dominant, severe disease characterized by progressive sensory-motor polyneuropathy, cardiomyopathy, dysautonomia, renal and eyes involvement, provoked by the deposition of the mutated and unstable transthyretin protein. In past decades, liver transplant, avoiding the synthesis of the pathologic protein, has been a good, even if not resolutive, treatment. In this report we describe two siblings affected with ATTRv, who developed first symptoms of disease at a young age and underwent a liver transplant with prompt resolution of clinical manifestations. After several years, central nervous system and eyes symptoms relapsed despite treatment, considering that the synthesis of mutated protein continues in choroid plexus, a locum where current therapies are unable to act. In our opinion, these cases represent a long-term prognostic model for the novel gene-silencers approved for ATTRv, because they share a similar therapeutic effect with liver transplant: the block of mutated protein synthesis limited only in the main transthyretin (TTR) production organ is able to prevent the progression of disease only for some years, but not to avoid long-term clinical worsening due to extra-hepatic production of TTR. Novel future therapeutic strategies are demanded to guarantee a better long-term stabilization of symptomatology.

Brain morphometry of preschool age children affected by autism spectrum disorder: Correlation with clinical findings.

The aim of our study was to use a combined imaging and clinical approach to identify possible patterns of clinical and imaging findings in a cohort of preschool age autism spectrum disorder (ASD) patients. In order to identify imaging patterns that could be related to specific clinical features, a selected group of ASD patients (age range 3-6 years) without dysmorphic features, epilepsy or other major neurological signs, malformations or other lesions at MRI was subjected to brain volumetric analysis using semiautomatic brain segmentation. An age-matched group of typically developing children was subjected to the same analysis. Our results were consistent with previous literature: Total gray matter volume, total cortical gray matter volume and amygdalar volumes were significantly greater in the ASD group than the control group. When we divided the study group into subgroups on the basis of clinical findings such as high- or low-functioning, or verbal and nonverbal, the only significant difference between verbal and nonverbal subjects was in cerebellar hemispheric size. In conclusions, our results confirm that newer brain MRI techniques using semiautomatic brain segmentation can provide information useful for defining the differences between ASD patients and controls, particularly if they form part of an integrated approach between MRI and cognitive-behavioral and genetic data. Clin. Anat. 32:143-150, 2019. © 2018 Wiley Periodicals, Inc. HIGHLIGHTS: Combined imaging and clinical approach in autism spectrum disorders Semiautomatic brain segmentation in a selected preschool age ASD group Reduced total cerebellar white matter volume in non-verbal ASD patients.

Three-dimensional rotational angiography for craniotomy planning and postintervention evaluation of intracranial aneurysms.

PURPOSE: The authors evaluated the usefulness of three-dimensional rotational angiography (3DRA) in surgical planning and postoperative evaluation of cerebral aneurysms. MATERIALS AND METHODS: A total of 111 consecutive aneurysms in 100 patients (32 emergency referrals due to haemorrhage) were evaluated with 3DRA over a period of 3 years. The rotational study was always performed with a single injection of 20 cc of contrast agent in the afferent vessel after diagnostic cerebral angiography in the two orthogonal projections. Three-dimensional reconstructions were obtained for the pre- and postoperative assessment. RESULTS: Three-dimensional RA provides a virtual view of the surgical field with the same orientation required for the surgical approach and, compared with surgical findings, reliably defined location, orientation, morphology and relationship with parent vessels of the aneurysm in all cases. Postoperatively, it allowed better assessment of any residual lesion and of the relationship between surgical clips and parent vessels, compared with standard 2D angiography. CONCLUSIONS: 3DRA is a reliable method for preliminary assessment of cerebral aneurysms undergoing surgery. It provides multiple projections with a preview of the surgical field and study of lesion characteristics, which can help achieve faster and safer surgery. Compared with 2D angiography, the 3D model, with its multiple views, allows better assessment of postoperative outcomes. The method also significantly reduces the number of angiographic projections and therefore radiation and contrast-medium dose to the patient.