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Vaccination strategies have been at the forefront of controlling the COVID-19 pandemic. An association between vaccine-induced immune thrombotic thrombocytopenia (VITT) and one of these vaccines, the ChAdOx1 nCov-19 vaccine, is now recognized. The purpose of this study was to investigate the frequency and location of thrombosis in each vascular system using CT, MRI, and US to identify additional sites of thrombus in a United Kingdom-wide sample of patients with confirmed VITT. Thirty-two radiology centers identified through the national collaborative Radiology Academic Network for Trainees were invited from the United Kingdom; seven of these contributed to this study. All patients with confirmed VITT ¬between February 3 and May 12, 2021, who met the inclusion criteria were included. The location and extent of thrombi were evaluated using CT, MRI, and US. A total of 40 patients (median age, 41 years [IQR, 32-52]; 22 [55%] men) with confirmed vaccine-induced immune thrombotic thrombocytopenia after administration of their first ChAdOx1 nCov-19 vaccine were included. Thirty-two patients (80%) developed symptoms within the first 14 days, and eight (20%) developed symptoms within 14-28 days. Twenty-nine patients (72%) experienced neurologic symptoms and were confirmed to have cerebral venous sinus thrombosis, 12 (30%) had clinical deterioration and repeat imaging demonstrated extension of their primary thrombus, and eight (20%) died. Twenty-five of 30 patients (83%) who underwent additional imaging had occult thrombosis. In conclusion, patients with VITT are likely to have multiple sites of thrombosis, with the most frequent being cerebral venous sinus thrombosis in combination with pulmonary embolism and portomesenteric venous thrombosis. Whole-body imaging with contrast-enhanced CT can be used to identify occult thrombosis.

Background: A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes. Methods: For this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 109 per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 μg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3–6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis. Findings: Between April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32–55) was lower than in the non-VITT group (57 years; 41–62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2–4) than non-VITT patients (two, 2–3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55 patients) compared with those who did not (11 [73%] of 15 patients; p=0·022). Interpretation: Cerebral venous thrombosis is more severe in the context of VITT. Non-heparin anticoagulants and immunoglobulin treatment might improve outcomes of VITT-associated cerebral venous thrombosis. Since existing criteria excluded some patients with otherwise typical VITT-associated cerebral venous thrombosis, we propose new diagnostic criteria that are more appropriate.

Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106 patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order to delineate the neuroradiological and clinical phenotype of patients with mutations in these genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who were negative on mutation analysis. We found a strong correlation (P

Author(s): Valente, E M; Brancat, F; Silhavy, J L; Castori, M; March, S E; Barrano, G; Bertini, E; Boltshauser, E; Zaki, M S; Abdel-Aleem, A; Abdel-Salam, GMH; Bellacchlo, E; Battini, R; Cruse, R P; Dobyns, W B; Krishnamoorthy, K S; Lagier-Tourenne, C; Magee, A; Pascual-Castroviejo, I; Salpietro, C D; Sarco, D; Dallapiccola, B; Gleeson, J G | Abstract: Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. It is characterized by hypoplasia of the cerebellar vermis and a particular midbrain-hindbrain "molar tooth" sign, a finding shared by a group of Joubert syndrome-related disorders (JSRDs), with wide phenotypic variability. The frequency of mutations in the first positionally cloned gene, AHI1, is unknown. Methods: We searched for mutations in the AHI1 gene among a cohort of 137 families with JSRD and radiographically proven molar tooth sign. Results: We identified 15 deleterious mutations in 10 families with pure JS or JS plus retinal and/or additional central nervous system abnormalities. Mutations among families with JSRD including kidney or liver involvement were not detected. Transheterozygous mutations were identified in the majority of those without history of consanguinity. Most mutations were truncating or splicing errors, with only one missense mutation in the highly conserved WD40 repeat domain that led to disease of similar severity. Interpretation AHI1 mutations are a frequent cause of disease in patients with specific forms of JSRD.