Fatal vaccine-induced immune thrombotic thrombocytopenia (VITT) post Ad26.COV2.S: first documented case outside US.

PURPOSE: We reported the first described post Ad26.COV2.S (Janssen, Johnson & Johnson) vaccine-induced immune thrombocytopenia (VITT) case outside US.  CASE DESCRIPTION: CA young woman without any medical history presented association of deep vein thrombosis and thrombocytopenia at day 10 after vaccine injection. The patient was treated with low-molecular weight heparin at a first medical institution. Twelve days post Ad26.COV2.S vaccination, the patient was admitted at our hospital for neurological deterioration and right hemiplegia. Medical imaging using MRI showed thrombosis of the major anterior part of the sagittal superior sinus with bilateral intraparenchymal hemorrhagic complications. Screening tests for antibodies against platelet factor 4 (PF4)-heparin by rapid lateral flow immunoassay and chemiluminescence techniques were negative. Platelet activation test using heparin-induced multiple electrode aggregometry confirmed the initial clinical hypothesis. Despite immediate treatment with intravenous immunoglobulin, dexamethasone, danaparoid and attempted neurosurgery the patient evolved toward brain death. CONCLUSION: Even though it is an extremely rare complication of vaccination physicians should maintain a high index of suspicion of VITT in patients who received an adenovirus-vector-based SARS-CoV-2 vaccine within the last 30 days with persistent complains compatible with VITT or thromboembolic event associated with thrombocytopenia. The diagnosis should not be excluded if the rapid anti-PF4 immunological nor chemiluminescence techniques yield negative results. An adapted functional assay should be performed to confirm the diagnosis. Early treatment with intravenous immunoglobulin and non-heparin anticoagulants is essential as delayed diagnosis and administration of appropriate treatment is associated with poor prognosis.

Hypothalamic Structural and Functional Imbalances in Anorexia Nervosa.

The hypothalamus contains integrative systems that support life, including physiological processes such as food intake, energy expenditure, and reproduction. Here, we show that anorexia nervosa (AN) patients, contrary to normal weight and constitutionally lean individuals, respond with a paradoxical reduction in hypothalamic levels of glutamate/glutamine (Glx) upon feeding. This reversal of the Glx response is associated with decreased wiring in the arcuate nucleus and increased connectivity in the lateral hypothalamic area, which are involved in the regulation on a variety of physiological and behavioral functions including the control of food intake and energy balance. The identification of distinct hypothalamic neurochemical dysfunctions and associated structural variations in AN paves the way for the development of new diagnostic and treatment strategies in conditions associated with abnormal body mass index and a maladaptive response to negative energy balance.

Coupled brain and urine spectroscopy - in vivo metabolomic characterization of HMG-CoA lyase deficiency in 5 patients.

BACKGROUND: 3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG-CoA) lyase deficiency is a rare inborn error of leucine metabolism and ketogenesis. Despite recurrent hypoglycemia and metabolic decompensations, most patients have a good clinical and neurological outcome contrasting with abnormal brain magnetic resonance imaging (MRI) signals and consistent abnormal brain proton magnetic resonance spectroscopy (1H-MRS) metabolite peaks. Identifying these metabolites could provide surrogate markers of the disease and improve understanding of MRI-clinical discrepancy and follow-up of affected patients. METHODS: Urine samples, brain MRI and 1H-MRS in 5 patients with HMG-CoA lyase deficiency (4 boys and 1 girl aged from 25days to 10years) were, for each patient, obtained on the same day. Brain and urine spectroscopy were performed at the same pH by studying urine at pH 7.4. Due to pH-induced modifications in chemical shifts and because reference 1H NMR spectra are obtained at pH 2.5, spectroscopy of normal urine added with the suspected metabolite was further performed at this pH to validate the correct identification of compounds. RESULTS: Mild to extended abnormal white matter MRI signals were observed in all cases. Brain spectroscopy abnormal peaks at 0.8-1.1ppm, 1.2-1.4ppm and 2.4ppm were also detected by urine spectroscopy at pH 7.4. Taking into account pH-induced changes in chemical shifts, brain abnormal peaks in patients were formally identified to be those of 3-hydroxyisovaleric, 3-methylglutaconic, 3-methylglutaric and 3-hydroxy-3-methylglutaric acids. CONCLUSION: 3-Methylglutaric, 3-hydroxyisovaleric and 3-hydroxy-3-methylglutaric acids identified on urine 1H-NMR spectra of 5 patients with HMG-CoA lyase deficiency are responsible for the cerebral spectroscopy signature seen in these patients, validating their local involvement in brain and putative contribution to brain neuropathology.

Update on neuroimaging phenotypes of mid-hindbrain malformations.

PURPOSE: Neuroimaging techniques including structural magnetic resonance imaging (MRI) and functional positron emission tomography (PET) are useful in categorizing various midbrain-hindbrain (MHB) malformations, both in allowing diagnosis and in helping to understand the developmental processes that were disturbed. Brain imaging phenotypes of numerous malformations are characteristic features that help in guiding the genetic testing in case of direct neuroimaging-genotype correlation or, at least, to differentiate among MHB malformations entities. The present review aims to provide the reader with an update of the use of neuroimaging applications in the fine analysis of MHB malformations, using a comprehensive, recently proposed developmental and genetic classification. METHODS: We have performed an extensive systematic review of the literature, from the embryology main steps of MHB development through the malformations entities, with regard to their molecular and genetic basis, conventional MRI features, and other neuroimaging characteristics. RESULTS: We discuss disorders in which imaging features are distinctive and how these features reflect the structural and functional impairment of the brain. CONCLUSION: Recognition of specific MRI phenotypes, including advanced imaging features, is useful to recognize the MHB malformation entities, to suggest genetic investigations, and, eventually, to monitor the disease outcome after supportive therapies.

Chédiak-Higashi syndrome: brain MRI and MR spectroscopy manifestations.

Chédiak-Higashi syndrome is a rare inherited metabolic disorder characterized by partial oculocutaneous albinism, immunodeficiency, and neurological dysfunction. We present the brain magnetic resonance imaging (MRI) and MR spectroscopy (MRS) findings obtained during the accelerated phase of the disorder in an 8-year-old. The brain MRI manifestations at recurrences 15 months and 24 months later are reported as well.

Age- and gender-related regional variations of human brain cortical thickness, complexity, and gradient in the third decade.

Brain functional and cytoarchitectural maturation continue until adulthood, but little is known about the evolution of the regional pattern of cortical thickness (CT), complexity (CC), and intensity or gradient (CG) in young adults. We attempted to detect global and regional age- and gender-related variations of brain CT, CC, and CG, in 28 healthy young adults (19-33 years) using a three-dimensional T1 -weighted magnetic resonance imaging sequence and surface-based methods. Whole brain interindividual variations of CT and CG were similar to that in the literature. As a new finding, age- and gender-related variations significantly affected brain complexity (P < 0.01) on posterior cingulate and middle temporal cortices (age), and the fronto-orbital cortex (gender), all in the right hemisphere. Regions of interest analyses showed age and gender significant interaction (P < 0.05) on the temporopolar, inferior, and middle temporal-entorrhinal cortices bilaterally, as well as left inferior parietal. In addition, we found significant inverse correlations between CT and CC and between CT and CG over the whole brain and markedly in precentral and occipital areas. Our findings differ in details from previous reports and may correlate with late brain maturation and learning plasticity in young adults' brain in the third decade.

Brain regional glucose uptake changes in isolated cerebellar cortical dysplasia: qualitative assessment using coregistrated FDG-PET/MRI.

We aimed to assess brain regional glucose uptake (rGlcU) changes in children with isolated cerebellar cortical dysplasia (CCD) using 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET). Six children aged 9 months to 11 years at the time of diagnosis, carrying isolated CCD (with no other associated posterior fossa or supratentorial malformation) underwent a brain FDG-PET and a subsequent 3DT1-weighted MRI for coregistration. The MRIs acquired previously at the time of diagnosis were reviewed to record the cerebellar dysplastic features and classify the patients as having minor, moderate, or severe CCD. The individual rGlcU was assessed qualitatively on coregistrated FDG maps. Clinical data from birth, including neurological and neuropsychological (verbal and motor skills) disturbances, were recorded. We found rGlcU changes within the cerebellum of four patients matching with the location and extent of structural abnormalities: hypometabolism in three patients with severe CCD involving the vermis and both cerebellar hemispheres and focal hypermetabolism in one patient with moderate CCD associated with a nodular heterotopic gray matter. No obvious rGlcU changes were found in the two patients with minor CCD involving the vermis only. Supratentorial rGlcU changes found commonly involved the basal ganglia bilaterally. Coregistrated FDG-PET/MRI technique is useful in detecting cerebellar cell dysfunction associated with isolated CCD. Our results enhance the need for multimodal and quantitative studies to better evaluate local and remote functional disturbances caused by CCD.

Multimodal imaging features of transient perivascular inflammation of the carotid artery (TIPIC) syndrome in a patient with Covid-19.

We report the case of a 38-year-old man with transient perivascular inflammation of the carotid artery syndrome that occurred in the course of covid-19. We describe for the first-time multimodal imaging features of the perivascular changes surrounding the carotid artery, and long-term follow-up by ultrasound. The imaging features observed on ultrasound, angiography-CT, MRI and FDG-Pet scan support the hypothesis of the inflammatory nature of the perivascular tissue thickening. The ultrasound follow-up confirmed the spontaneous resolution of the lesion, leaving on site some residual changes as sequelae. The good knowledge of the imaging features reported herein helps to recognize this entity in patients with covid-19.

Neuropsychological evaluation and follow-up of children with cerebellar cortical dysplasia.

AIM: To describe neuropsychological disturbances and the developmental course associated with cerebellar cortical dysplasia (CCD). METHOD: The neuroimaging findings from 10 children (five males, five females; aged 3-10 y) with CCD were reviewed and classified. These children all underwent clinical neurological examination and neuropsychological assessment (NPA) on admission, then were followed for an average of 6 years using the cognitive Wechsler Scale, Vineland Adaptive Behavior Scales, and Rey-Osterrieth Complex Figure/McCarthy Drawing subtests. RESULTS: Based on magnetic resonance imaging, CCD was categorized as minor (n = 4), moderate (n = 1), and severe (n = 5). The first NPA disclosed mental retardation* in six (profound, three; moderate, one; mild, two) and normal intelligence in four (low, two; average, one; high, one), but with verbal/performance dissociation in three cases. Socio-adaptive functions were altered in all children except one. Visuospatial abilities were delayed in eight children. In the follow-up, no progression was observed in the three cases with profound mental retardation, whereas the remainder showed homogeneous or disharmonic progression, including improvement or deterioration of verbal/performance function. Cognitive impairment and evolution was not associated with the degree of cerebellar involvement. INTERPRETATION: The neuropsychological profile and evolution associated with CCD do not appear to be predictable, and some features might improve over time.

Hemangioblastoma: An Unsuspected Pitfall in PSMA PET/CT.

ABSTRACT: Hemangioblastoma (HB) is the most common primary intra-axial posterior fossa tumor in adults and is a benign vascular neoplasm. We report the case of a 73-year-old man suffering from biochemical recurrence of prostate cancer where intense overexpression of prostate-specific membrane antigen (PSMA) was observed in HB in a PSMA PET/CT. Overexpression of PSMA in tumor-associated vascular structures has been proposed as an explanation of PSMA ligand uptake in several nonprostatic tumors. Given the pathological nature of HB, this mechanism may explain the intense overexpression of PSMA observed in present case.

Postmeningitis subdural fluid collection in infants: changing pattern and indications for surgery.

OBJECT: Postmeningitis subdural fluid collection (PMSFC) is a classic complication of bacterial meningitis in infants. When the diagnosis was based solely on subdural puncture (SDP), its incidence was estimated to be as high as one half of the cases of meningitis, with Haemophilus influenzae as the most common causative bacterium. Knowledge concerning the diagnostic and bacteriological characteristics of PMSFC has expanded greatly since the introduction of computerized imaging and the use of the anti-H. influenzae vaccine; however, in no recent study have the authors reappraised this clinical entity with regard to diagnosis, bacteriology, and indications for surgery. METHODS: The authors reviewed their cases of PMSFC in infants in which a diagnosis was made based on computerized tomography findings and confirmed with SDP. They treated PMSFC using placement of a subdural drain whenever the collection was either clinically eloquent or exerted a mass effect on the brain. In the 26 years preceding the study, the authors had treated 29 patients younger than 16 months of age for PMSFC. Eight patients required SDP only, 20 underwent surgical drainage, and five required craniotomy. In six cases, the fluid was grossly purulent; in the others, it was clear, xanthochromatic, or hemorrhagic. Cultures were positive for Streptococcus pneumoniae in only two cases. Although H. influenzae was the most common bacterium at the beginning of the series, Neisseria meningitidis has become more prevalent since vaccination against the former became widespread. Based on their data the authors estimate that 5% of N. meningitidis infections in infants are complicated by a significant PMSFC. CONCLUSIONS: At present, PMSFCs are most often caused by N. meningitidis. Temporary surgical drain placement is advised for all cases in which a significant mass effect is apparent on imaging.

Midbrain-hindbrain involvement in lissencephalies.

OBJECTIVES: To determine the involvement of the midbrain and hindbrain (MHB) in the groups of classic (cLIS), variant (vLIS), and cobblestone complex (CBSC) lissencephalies and to determine whether a correlation exists between the cerebral malformation and the MHB abnormalities. METHODS: MRI scans of 111 patients (aged 1 day to 32 years; mean 5 years 4 months) were retrospectively reviewed. After reviewing the brain involvement on MRI, the cases were reclassified according to known mutation (LIS1, DCX, ARX, VLDLR, RELN, MEB, WWS) or mutation phenotype (LIS1-P, DCX-P, RELN-P, ARX-P, VLDLR-P) determined on the basis of characteristic MRI features. Abnormalities in the MHB were then recorded. For each structure, a score was assigned, ranging from 0 (normal) to 3 (severely abnormal). The differences between defined groups and the correlation between the extent of brain agyria/pachygyria and MHB involvement were assessed using Kruskal-Wallis and chi(2) McNemar tests. RESULTS: There was a significant difference in MHB appearance among the three major groups of cLIS, vLIS, and CBSC. The overall score showed a severity gradient of MHB involvement: cLIS (0 or 1), vLIS (7), and CBSC (11 or 12). The extent of cerebral lissencephaly was significantly correlated with the severity of MHB abnormalities (p = 0.0029). CONCLUSION: Our study focused on posterior fossa anomalies, which are an integral part of cobblestone complex lissencephalies but previously have not been well categorized for other lissencephalies. According to our results and the review of the literature, we propose a new classification of human lissencephalies.