In recent years, gadolinium-based contrast agents have been associated with different types of toxicity. In particular, nephrogenic systemic fibrosis, a progressive sclerotic-myxedematous systemic ...disease of unknown etiology, is related to gadolinium-based contrast agent administration in patients with kidney dysfunction. More recently, evidence of magnetic resonance signal intensity changes on pre-contrast T1-weighted images after multiple gadolinium-based contrast agent administrations resulted in the hypothesis of gadolinium brain accumulation in patients with normal renal function, subsequently confirmed in pathological samples. However, there is limited current data and further investigations are necessary before drawing definite conclusions on the clinical consequences of gadolinium-based contrast agent accumulation in human tissues and particularly in the brain. Gadolinium-based contrast agent-related toxicity appears connected to molecular stability, which varies together with the pharmacokinetic properties of the compound and depends on the individual characteristics of the subject. During a lifetime, the physiological changes occurring in the human body may influence its interaction with gadolinium-based contrast agents: the integrity and developmental stage of the organs has an effect on the dynamics of gadolinium-based contrast agent distribution and excretion, thus leading to different possible mechanisms of deposition and toxicity. Therefore, the aim of this work is to discuss the pharmacokinetics and pharmacodynamics of gadolinium-based contrast agents, with a special focus on the brain, and to explore potential predominant gadolinium-based contrast agent-related toxicity in two cornerstone periods of the human life cycle: fetal/neonatal and adulthood/aged.
Neurite Orientation Dispersion and Density Imaging (NODDI) and Bingham-NODDI diffusion MRI models are nowadays very well-known models in the field of diffusion MRI as they represent powerful tools ...for the estimation of brain microstructure. In order to efficiently translate NODDI imaging findings into the diagnostic clinical practice, a test-retest approach would be useful to assess reproducibility and reliability of NODDI biomarkers, thus providing validation on precision of different fitting toolboxes. In this context, we conducted a test-retest study with the aim to assess the effects of different factors (i.e. fitting algorithms, multiband acceleration, shell configuration, age of subject and hemispheric side) on diffusion models reliability, assessed in terms of Intra-class Correlation Coefficient (ICC) and Variation Factor (VF). To this purpose, data from pediatric and adult subjects were acquired with Simultaneous-MultiSlice (SMS) imaging method with two different acceleration factor (AF) and four b-values, subsequently combined in seven shell configurations. Data were then fitted with two different GPU-based algorithms to speed up the analysis. Results show that each factor investigated had a significant effect on reliability of several diffusion parameters. Particularly, both datasets reveal very good ICC values for higher AF, suggesting that faster acquisitions do not jeopardize the reliability and are useful to decrease motion artifacts. Although very small reliability differences appear when comparing shell configurations, more extensive diffusion parameters variability results when considering shell configuration with lower b-values, especially for simple model like NODDI. Also fitting tools have a significant effect on reliability, but their difference occurs in both datasets and AF, so it appears to be independent from either misalignment and motion artifacts, or noise and SNR. The main achievement of the present study is to show how 10 min multi-shell diffusion MRI acquisition for NODDI acquisition can have reliable results in WM. More complex models do not appear to be more prone to less data acquisition as well as noisier data thus stressing the idea of Bingham-NODDI having greater sensitivity to true subject variability.
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a worldwide prevalence of about 1%, characterized by impairments in social interaction, communication, repetitive patterns ...of behaviors, and can be associated with hyper- or hypo-reactivity of sensory stimulation and cognitive disability. ASD comorbid features include internalizing and externalizing symptoms such as anxiety, depression, hyperactivity, and attention problems. The precise etiology of ASD is still unknown and it is undoubted that the disorder is linked to some extent to both genetic and environmental factors. It is also well-documented and known that one of the most striking and consistent finding in ASD is the higher prevalence in males compared to females, with around 70% of ASD cases described being males. The present review looked into the most significant studies that attempted to investigate differences in ASD males and females thus trying to shade some light on the peculiar characteristics of this prevalence in terms of diagnosis, imaging, major autistic-like behavior and sex-dependent uniqueness. The study also discussed sex differences found in animal models of ASD, to provide a possible explanation of the neurological mechanisms underpinning the different presentation of autistic symptoms in males and females.
Ethylmalonic encephalopathy (EE) is a severe intoxication-type metabolic disorder with multisystem clinical features and leading to early death. In 2014, based on the promising results obtained by ...liver-targeted gene therapy in Ethe1
mouse model, we successfully attempted liver transplantation in a 9-month-old EE girl. Here we report her long-term follow-up, lasting over 6 years, with a comprehensive evaluation of clinical, instrumental and biochemical assessments.
Neurological signs initially reverted, with a clinical stabilization during the entire follow-up course. Accordingly, gross motor functions improved and then stabilized. Psychomotor evaluations documented an increasing communicative intent, the acquisition of new social skills and the capability to carry out simple orders. Neurophysiological assessments, which included EEG, VEP/ERG and BAEPs, remained unchanged. Brain MRI also stabilized, showing no further lesions and cerebral atrophy improvement. Compared to pre-transplant assessments, urinary ethylmalonic acid strikingly reduced, and plasma thiosulphate fully normalized. The child maintained good clinical conditions and never experienced metabolic crises nor epileptic seizures.
The long-term follow-up of the first EE transplanted patient demonstrates that liver transplantation stabilizes, or even improves, disease course, therefore representing a potentially elective option especially in early-diagnosed patients, such as those detected by newborn screening, before irreversible neurological damage occurs.
We conducted a GIS spatial analysis with the aim of providing the first quantitative large-scale overview of the distribution patterns of 1536 type localities (loci classici) of 1216 Italian endemic ...vascular plants and their relationship with a set of descriptive variables. Whereas some variables were used to model the presence-absence distribution patterns of the type localities for the whole set of endemics as well as for the subset of narrow endemics, others (e.g., presence inside or outside protected areas and Italian Important Plant Areas) were considered with the purpose of assessing potential assets or risks for conservation.
The largest number of type localities was found within the Mediterranean biogeographic region (1134), followed by the Alpine region (306) and Continental region (96). A total of 670 locations are located on islands, whereas 866 are located on the Italian mainland (139 and 124 in the case of narrow endemics, respectively). A large number of type localities are located in mountainous areas and along the coastline, which can be seen as a potential risk for conservation. On the contrary, we detected a positive correlation with the distance from roads, which might be considered to be an asset. Importantly, 1030 type localities fall inside protected areas, whereas 506 localities fall outside protected areas, with 259 of these unprotected localities on islands.
We propose considering the results of the analysis of the distribution of type localities of Italian endemics to be a strategic tool for conservation planning and resource management. Application of plant micro-reserves and integration of diverse legislation tools are suggested to strengthen efforts and increase conservation success.
•We provide the first large sale study on the distribution of 1536 type localities of Italian endemic plant species•We highlight main drivers of distribution and major assets and for the conservation of type localities•The distribution of the type localities should be taken into account in conservation planning
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare disorder of urea cycle characterized by progressive pyramidal and cerebellar dysfunction, whose pathophysiology is not yet ...fully understood. Here we describe the spectrum of the long fibers involvement in HHH syndrome, attempting a correlation between clinical, electrophysiological and neuro-radiological data.
Nine HHH patients were longitudinally evaluated by clinical examination, neurophysiological assessment including motor (MEPs), somato-sensory evoked potentials (PESS) and nerve conduction velocity (NCV), brain and spinal cord MRI RESULTS: All patients had pyramidal dysfunction and 3/9 an overt spastic paraplegia. Mild to moderate cerebellar signs were found in 7/9, intellectual disability in 8/9. At lower limbs, MEPs resulted abnormal in 7/8 patients and PESS in 2/8; peripheral sensory-motor neuropathy was found in 1/9. MRI documented atrophic changes in supra-tentorial brain regions in 6/9 patients, cerebellum in 6/9, spinal cord in 3/7.
A predominant corticospinal dysfunction is evident in HHH syndrome, along with milder cerebellar signs, intellectual disability of variable degree and rare peripheral neuropathy. Phenotypical similarities with other disorders affecting the urea cycle (argininemia and pyrroline-5-carboxylate synthetase deficiency) suggest possible common mechanisms contributing in the maintenance of the corticospinal tract integrity. HHH syndrome phenotype largely overlaps with complex Hereditary Spastic Paraplegias (HSPs), in the list of which it should be included, emphasizing the importance to screen all the unsolved cases of HSPs for metabolic biomarkers.
Purpose
Spinal cord involvement in Kearns-Sayre (KSS) syndrome could be more frequent than commonly thought. Our aims were to evaluate the involvement of the spinal cord in patients with KSS by means ...of MRI and to investigate possible correlations of spinal and brain disease with patient disability.
Methods
Eleven patients with KSS disease and spinal cord MRI were retrospectively recruited. The severity of spinal disease was defined as follows: grade 0 (none), grade 1 (focal), and grade 2 (extensive). We calculated a radiologic score of brain involvement based on typical features. We performed a chi-square test to correlate spinal cord and brain MRI involvement to patient disability. For significant variables, a contingency coefficient, phi factor, and Cramer’s
V
were also computed.
Results
Spinal cord lesions were detected in 6/11 patients, showing four patterns: involvement of gray matter, gray matter and posterior columns, posterior columns, and anterior columns. The severity of spinal disease was grade 1 in two and grade 2 in four patients. All patients showed brain involvement (9-point average for patients with spinal involvement and 10 for the others). A significant correlation was found between disability score and spinal cord involvement (
χ
2
= 7.64;
p
= 0.022) or brain score (
χ
2
= 26.85;
p
= 0.043). Significance for brain score-disability correlation increased with the spinal cord as a cofactor (
χ
2
= 24.51;
p
= 0.017, phi factor = 1.201, Cramer’s
V
= 0.849, contingency effect = 0.767;
p
= 0.017).
Conclusion
Spinal cord lesions are common in KSS. Patients with spinal disease show higher disability than patients without spinal cord lesions, supporting the inclusion of dedicated acquisitions to routine MRI of the brain in patients with KSS.
Hydatiform mole occurs in 1/1000 singleton and 1/20000–100,000 twin pregnancies. Although the pregnancy often ends in a miscarriage or presents with many obstetric complications such as preeclampsia, ...vaginal bleeding, hyperthyroidism, prematurity, or fetal malformations, in some cases of twin pregnancy, one of the fetuses can develop normally. Coexistence of a viable fetus in a twin molar pregnancy is more commonly described for cases of complete hydatiform moles than partial hydatiform moles. A partial hydatiform mole coexisting with a normal fetus was suspected in a 40-year-old woman, G2P1, at twelve weeks of gestation of a twin dichorionic diamniotic pregnancy. Serial antenatal ultrasound scans and serial evaluations of human chorionic gonadotropin were performed, and a healthy baby was delivered at term without any obstetric or neonatal complications.
A twin pregnancy with partial hydatidiform mole and a coexisting normal fetus is a rare obstetric condition that can result, under proper management, in the delivery of a healthy baby without any sequelae for the mother or child.
A 40-years-old, Caucasian, G2P1 woman which pregnancy was complicated by a partial hydatiform mole and a coexisting normal fetus, succeded, under proper management, to have a vaginal delivery at term and a healthy baby, without any obstetrical nor neonatal complications.
Moreover, the pregnancy was completely uneventful and no evidence of persistent trophoblastic disease was noticed at follow-up. Display omitted
•Hydatiform mole is a very rare condition, especially for twin pregnancies.•It often ends in a miscarriage or presents many obstetrics complications.•Hydatiform mole can progress to gestational trophoblastic neoplasia.•The evaluation of beta human chorionic gonadotropin (BhCG) is crucial in the diagnosis and the management of hydatiform mole.•A twin pregnancy with coexistence of mole and fetus can result in a healthy baby.
There is growing interest in studying human brain connectivity and in modelling the brain functional structure as a network. Brain network creation requires parcellation of the cerebral cortex to ...define nodes. Parcellation might be affected by possible errors due to inter- and intra-subject variability as a consequence of brain structural and physiological characteristics and shape variations related to ageing and diseases, acquisition noise, and misregistration. These errors could induce a knock-on effect on network measure variability. The aim of this study was to investigate spatial stability, a measure of functional connectivity variations induced by parcellation errors. We simulated parcellation variability with random small spatial changes and evaluated its effects on twenty-seven graph-theoretical measures. The study included subjects from three public online datasets. Two brain parcellations were performed using FreeSurfer with geometric atlases. Starting from these, 100 new parcellations were created by increasing the area of 30% of parcels, reducing the area of neighbour parcels, with a rearrangement of vertices. fMRI data were filtered with linear regression, CompCor, and motion correction. Adjacency matrices were constructed with 0.1, 0.2, 0.3, and 0.4 thresholds. Differences in spatial stability between datasets, atlases, and threshold were evaluated. The higher spatial stability resulted for Characteristic-path-length, Density, Transitivity, and Closeness-centrality, and the lower spatial stability resulted for Bonacich and Katz. Multivariate analysis showed a significant effect of atlas, datasets, and thresholds. Katz and Bonacich centrality, which was subject to larger variations, can be considered an unconventional graph measure, poorly implemented in the clinical field and not yet investigated for reliability assessment. Spatial stability (SS) is affected by threshold, and it decreases with increasing threshold for several measures. Moreover, SS seems to depend on atlas choice and scanning parameters. Our study highlights the importance of paying close attention to possible parcellation-related spatial errors, which may affect the reliability of functional connectivity measures.
Protocadherin-19 (PCDH19) developmental and epileptic encephalopathy causes an early-onset epilepsy syndrome with limbic seizures, typically occurring in clusters and variably associated with ...intellectual disability and a range of psychiatric disorders including hyperactive, obsessive-compulsive and autistic features. Previous quantitative neuroimaging studies revealed abnormal cortical areas in the limbic formation (parahippocampal and fusiform gyri) and underlying white-matter fibers. In this study, we adopted morphometric, network-based and multivariate statistical methods to examine the cortex and substructure of the hippocampus and amygdala in a cohort of 20 PCDH19-mutated patients and evaluated the relation between structural patterns and clinical variables at individual level. We also correlated morphometric alterations with known patterns of PCDH19 expression levels. We found patients to exhibit high-significant reductions of cortical surface area at a whole-brain level (left/right p
= 0.045/0.084), and particularly in the regions of the limbic network (left/right parahippocampal gyri p
= 0.230/0.016; left/right entorhinal gyri p
= 0.002/0.327), and bilateral atrophy of several subunits of the amygdala and hippocampus, particularly in the CA regions (head of the left CA3 p
= 0.002; body of the right CA3 p
= 0.004), and differences in the shape of hippocampal structures. More severe psychiatric comorbidities correlated with more significant altered patterns, with the entorhinal gyrus (p
= 0.013) and body of hippocampus (p
= 0.048) being more severely affected. Morphometric alterations correlated significantly with the known expression patterns of PCDH19 (r
= -0.26, p
= 0.092). PCDH19 encephalopathy represents a model of genetically determined neural network based neuropsychiatric disease in which quantitative MRI-based findings correlate with the severity of clinical manifestations and had have a potential predictive value if analyzed early.
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