Oral self-inflicted accidental trauma in patients with neurological disorders: a case report of dental management in infants with cerebellar hypoplasia.

Self-inflicted oral injuries, accidental or otherwise, can cause major consequences. Measures need to be taken to protect individuals from chronic self-injurious behaviour; however, there are no official guidelines on the subject. The purpose of this article is to show the case of a 1-year-old patient with neurological disorders who, following the eruption of deciduous teeth, had self-inflicted a traumatic ulcer on his tongue and lower lip. Following a multidisciplinary approach involving several operating units of our hospital to make a diagnosis, an oral device was designed to completely cover the dental elements to prevent recurrence of the trauma and to prevent further worsening of the injuries already caused. The purpose of this work is to demonstrate that although the surgical approach, such as extraction of the dental elements, may be the quickest solution in situations similar to the one presented, the high biological cost and irreversibility of the result lead to seeking alternatives and more conservative solutions such as the one described.

Magnetic resonance imaging based neurosurgical planning on hololens 2: A feasibility study in a paediatric hospital.

Objective: The goal of this work is to show how to implement a mixed reality application (app) for neurosurgery planning based on neuroimaging data, highlighting the strengths and weaknesses of its design. Methods: Our workflow explains how to handle neuroimaging data, including how to load morphological, functional and diffusion tensor imaging data into a mixed reality environment, thus creating a first guide of this kind. Brain magnetic resonance imaging data from a paediatric patient were acquired using a 3 T Siemens Magnetom Skyra scanner. Initially, this raw data underwent specific software pre-processing and were subsequently transformed to ensure seamless integration with the mixed reality app. After that, we created three-dimensional models of brain structures and the mixed reality environment using Unity™ engine together with Microsoft® HoloLens 2™ device. To get an evaluation of the app we submitted a questionnaire to four neurosurgeons. To collect data concerning the performance of a user session we used Unity Performance Profiler. Results: The use of the interactive features, such as rotating, scaling and moving models and browsing through menus, provided by the app had high scores in the questionnaire, and their use can still be improved as suggested by the performance data collected. The questionnaire's average scores were high, so the overall experiences of using our mixed reality app were positive. Conclusion: We have successfully created a valuable and easy-to-use neuroimaging data mixed reality app, laying the foundation for more future clinical uses, as more models and data derived from various biomedical images can be imported.

A New Pattern of Brain and Cord Gadolinium Enhancement in Molybdenum Cofactor Deficiency: A Case Report.

Molybdenum cofactor deficiency (MoCD) is a rare and severe autosomal recessive in-born error of metabolism caused by the mutation in MOCS1, MOCS2, MOCS3 or GEPH genes, with an incidence ranging between 1 in 100,000 and 200,000 live births. The clinical presentation with seizures, lethargy and neurologic deficits reflects the neurotoxicity mediated via sulphite accumulation, and it occurs within the first hours or days after birth, often leading to severe neurodegeneration and the patient's death within days or months. The Imaging of Choice is a brain-specific MRI technique, which is usually performed without contrast and shows typical radiological findings in the early phase, such as diffuse cerebral oedema and infarction affecting the cortex and the basal ganglia and the white matter, as well as in the late phase, such as multicystic encephalomalacia. Our case report represents a novelty in the field, since the patient underwent a contrast-enhanced MRI to exclude a concomitant infectious disease. In the frame of the clinical presentation and laboratory data, we describe the MoCD Imaging findings for MRI morphological and advanced sequences, presenting a new contrast-enhanced MRI pattern characterized by the diffuse and linear leptomeningeal enhancement of brain, cord and spinal roots. The early identification of molybdenum cofactor deficiency is crucial because it may lead to the best multidisciplinary therapy for the patient, which is focused on the prompt and optimal management of the complications.

A Case Report of Pediatric Patient with Tuberous Sclerosis and Radiologically Isolated Syndrome.

INTRODUCTION: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease with central nervous system (CNS) involvement. Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS characterized by symptomatic episodes that occur months or years apart and affect different anatomic locations. In the absence of symptomatic episodes, radiologically isolated syndrome (RIS) could be diagnosed. Here, we report the case of a 10-year-old boy followed-up for TSC and diagnosed with RIS after a routine neuroimaging assessment. CASE DESCRIPTION: The patient was diagnosed with TSC after seizure onset at the age of 4 years. The follow-up magnetic resonance imaging (MRI) showed multiple asymptomatic demyelinating lesions. Brain and spinal cord MRI was performed after 2 months and showed additional lesions in the right frontal white matter and left cerebral peduncle, the latter with contrast enhancement. Therefore, he received a diagnosis of RIS. Visual evoked potentials were normal. Cerebrospinal fluid examination showed oligoclonal bands. The search for AQP4-IgG and MOG-IgG antibodies was negative. He was treated with interferon beta-1a. Six months later, follow-up MRI revealed no new demyelinating lesions and resolution of contrast enhancement. CONCLUSION: To the best of our knowledge, this is the third reported patient presenting a co-occurrence of TSC and demyelinating disease. Although we cannot state if the described comorbidity is casual or not, some clinical and preclinical data suggest that the mTOR complex might be the link between TSC and demyelinating disease.

The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of SON Gene Focusing on Liver Involvement: Patient Report and Literature Review.

Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in SON. Haploinsufficiency in SON may affect multiple genes, including those involved in the development and metabolism of multiple organs. Considering the broad spectrum of SON functions, it is to be expected that pathogenic variants in this gene can cause a wide spectrum of clinical symptoms. We present an additional ZTTK syndrome case due to a de novo heterozygous variant in the SON gene (c.5751_5754delAGTT). The clinical manifestations of our patient were similar to those present in previously reported cases; however, the diagnosis of ZTTK syndrome was delayed for a long time and was carried out during the diagnostic work-up of significant chronic liver disease (CLD). CLD has not yet been reported in any series; therefore, our report provides new information on this rare condition and suggests the expansion of the ZTTK syndrome phenotype, including possible liver involvement. Correspondingly, we recommend screening patients with SON variants specifically for liver involvement from the first years of life. Once the CLD has been diagnosed, an appropriate follow-up is mandatory, especially considering the role of SON as an emerging player in cancer development. Further studies are needed to investigate the role of SON haploinsufficiency as a downregulator of essential genes, thus potentially impairing the normal development and/or functions of multiple organs.

From Fetal to Neonatal Neuroimaging in TORCH Infections: A Pictorial Review.

Congenital infections represent a challenging and varied clinical scenario in which the brain is frequently involved. Therefore, fetal and neonatal neuro-imaging plays a pivotal role in reaching an accurate diagnosis and in predicting the clinical outcome. Congenital brain infections are characterized by various clinical manifestations, ranging from nearly asymptomatic diseases to syndromic disorders, often associated with severe neurological symptoms. Brain damage results from the complex interaction among the infectious agent, its specific cellular tropism, and the stage of development of the central nervous system at the time of the maternal infection. Therefore, neuroradiological findings vary widely and are the result of complex events. An early detection is essential to establishing a proper diagnosis and prognosis, and to guarantee an optimal and prompt therapeutic perinatal management. Recently, emerging infective agents (i.e., Zika virus and SARS-CoV2) have been related to possible pre- and perinatal brain damage, thus expanding the spectrum of congenital brain infections. The purpose of this pictorial review is to provide an overview of the current knowledge on fetal and neonatal brain neuroimaging patterns in congenital brain infections used in clinical practice.

COVID Mortality Prediction with Machine Learning Methods: A Systematic Review and Critical Appraisal.

More than a year has passed since the report of the first case of coronavirus disease 2019 (COVID), and increasing deaths continue to occur. Minimizing the time required for resource allocation and clinical decision making, such as triage, choice of ventilation modes and admission to the intensive care unit is important. Machine learning techniques are acquiring an increasingly sought-after role in predicting the outcome of COVID patients. Particularly, the use of baseline machine learning techniques is rapidly developing in COVID mortality prediction, since a mortality prediction model could rapidly and effectively help clinical decision-making for COVID patients at imminent risk of death. Recent studies reviewed predictive models for SARS-CoV-2 diagnosis, severity, length of hospital stay, intensive care unit admission or mechanical ventilation modes outcomes; however, systematic reviews focused on prediction of COVID mortality outcome with machine learning methods are lacking in the literature. The present review looked into the studies that implemented machine learning, including deep learning, methods in COVID mortality prediction thus trying to present the existing published literature and to provide possible explanations of the best results that the studies obtained. The study also discussed challenging aspects of current studies, providing suggestions for future developments.

Cryptococcal Meningitis and Post-Infectious Inflammatory Response Syndrome in a Patient With X-Linked Hyper IgM Syndrome: A Case Report and Review of the Literature.

The hyper IgM syndromes are a rare group of primary immunodeficiency. The X-linked Hyper IgM syndrome (HIGM), due to a gene defect in CD40L, is the commonest variant; it is characterized by an increased susceptibility to a narrow spectrum of opportunistic infection. A few cases of HIGM patients with Cryptococcal meningoencephalitis (CM) have been described in the literature. Herein we report the case of a young male diagnosed in infancy with HIGM who developed CM complicated by a post-infectious inflammatory response syndrome (PIIRS), despite regular immunoglobulin replacement therapy and appropriate antimicrobial prophylaxis. The patient was admitted because of a headache and CM was diagnosed through detection of Cryptococcus neoformans in the cerebrospinal fluid. Despite the antifungal therapy resulting to negative CSF culture, the patient exhibited persistent headaches and developed diplopia. An analysis of inflammatory cytokines on CSF, as well as the brain MRI, suggested a diagnosis of PIIRS. Therefore, a prolonged corticosteroids therapy was started obtaining a complete resolution of symptoms without any relapse.

Early alterations of cortical thickness and gyrification in migraine without aura: a retrospective MRI study in pediatric patients.

BACKGROUND: Migraine is the most common neurological disease, with high social-economical burden. Although there is growing evidence of brain structural and functional abnormalities in patients with migraine, few studies have been conducted on children and no studies investigating cortical gyrification have been conducted on pediatric patients affected by migraine without aura. METHODS: Seventy-two pediatric patients affected by migraine without aura and eighty-two controls aged between 6 and 18 were retrospectively recruited with the following inclusion criteria: MRI exam showing no morphological or signal abnormalities, no systemic comorbidities, no abnormal neurological examination. Cortical thickness (CT) and local gyrification index (LGI) were obtained through a dedicated algorithm, consisting of a combination of voxel-based and surface-based morphometric techniques. The statistical analysis was performed separately on CT and LGI between: patients and controls; subgroups of controls and subgroups of patients. RESULTS: Patients showed a decreased LGI in the left superior parietal lobule and in the supramarginal gyrus, compared to controls. Female patients presented a decreased LGI in the right superior, middle and transverse temporal gyri, right postcentral gyrus and supramarginal gyrus compared to male patients. Compared to migraine patients younger than 12 years, the ≥ 12-year-old subjects showed a decreased CT in the superior and middle frontal gyri, pre- and post-central cortex, paracentral lobule, superior and transverse temporal gyri, supramarginal gyrus and posterior insula. Migraine patients experiencing nausea and/or vomiting during headache attacks presented an increased CT in the pars opercularis of the left inferior frontal gyrus. CONCLUSIONS: Differences in CT and LGI in patients affected by migraine without aura may suggest the presence of congenital and acquired abnormalities in migraine and that migraine might represent a vast spectrum of different entities. In particular, ≥ 12-year-old pediatric patients showed a decreased CT in areas related to the executive function and nociceptive networks compared to younger patients, while female patients compared to males showed a decreased CT of the auditory cortex compared to males. Therefore, early and tailored therapies are paramount to obtain migraine control, prevent cerebral reduction of cortical thickness and preserve executive function and nociception networks to ensure a high quality of life.

Clinical and neuroimaging characteristics of MOG autoimmunity in children with acquired demyelinating syndromes.

Background Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been recently reevaluated as a biomarker of acquired demyelinating syndromes (ADS) of the central nervous system (CNS). Here, we describe the clinical and neuroimaging features, and the long-term outcome of children with ADS of the CNS associated with MOG-IgG. Methods All patients underwent brain and spinal cord magnetic resonance imaging (MRI), lumbar puncture for cerebrospinal fluid (CSF) analysis and MOG-IgG and aquaporin-4 IgG (AQP4-IgG) testing. Results Forty-eight pediatric patients were recruited. MOG-IgG were detected in 11/48 (25%) patients with the following clinical presentations: encephalomyelitis (EM), 8/11 (73%); optic neuritis (ON), 2/11 (18%); transverse myelitis (TM), 1/11 (9%). Patients negative for MOG-IgG were diagnosed with Multiple Sclerosis (MS) (n=15), EM (n=7), ON (n=7), neuromyelitis optica spectrum disorders (NMOSD) (n=5), TM (n=2) and encephalitis (n=1). MOG-IgG positive patients were younger at disease onset and they more frequently experienced encephalopathy and epileptic seizures compared with negative patients. EM and inflammatory lesions involving optic nerves on MRI imaging were more frequent in MOG-IgG positive patients. None of the patients with MOG-IgG became persistently seronegative during the follow-up, although a decrease in MOG-IgG titer was observed. Patients with MOG-IgG showed a good response to therapy and only two patients presented relapses during follow-up. Conclusion This study supports the distinction of MOG autoimmune oligodendrocytopathy as a unique disease entity, with clinical features different from those of MS and AQP4-IgG-positive NMOSD.

Pediatric Neuromyelitis Optica Spectrum Disorder: Case Series and Literature Review.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a central nervous system (CNS) inflammatory demyelinating disease characterized by recurrent inflammatory events that primarily involve optic nerves and the spinal cord, but also affect other regions of the CNS, including hypothalamus, area postrema and periaqueductal gray matter. The aquaporin-4 antibody (AQP4-IgG) is specific for NMOSD. Recently, myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been found in a group of AQP4-IgG negative patients. NMOSD is rare among children and adolescents, but early diagnosis is important to start adequate therapy. In this report, we present cases of seven pediatric patients with NMOSD and we review the clinical and neuroimaging characteristics, diagnosis, and treatment of NMOSD in children.

Spatial Stability of Functional Networks: A Measure to Assess the Robustness of Graph-Theoretical Metrics to Spatial Errors Related to Brain Parcellation.

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.

A new MRI severity score to predict long-term adverse neurologic outcomes in children with congenital Cytomegalovirus infection.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is one of the main causes of deafness in childhood. It frequently causes serious long-term neurological sequelae. In children who are asymptomatic at birth, tests to accurately predict these sequelae are still unavailable. AIMS: We describe different brain MRI patterns of congenital CMV infection correlated with clinical data and propose a new MRI severity score to early predict long-term neurological sequelae. MATERIALS AND METHODS: We explored clinical records and neuroimaging data of 224 neonates and children with congenital Cytomegalovirus infection, 180 of them did not meet inclusion criteria. Forty-four babies met inclusion criteria and were enrolled in the study. We retrospectively collected clinical data concerning hospitalization, 2 years outpatient follow-up and brain MRI findings of those 44 children, symptomatic and asymptomatic at birth. Clinical data were then correlated with children's brain MRI examinations. We defined neurological and sensorial impairment (hearing or visual) as "adverse neurological outcomes". Brain MRI score was constructed assigning different values to white matter and ventricular dilation. RESULTS: In 44 children enrolled in the study we found that 28/35 (80%) with abnormal and 2/9 (22,2%) with normal MRI examination developed adverse neurological outcomes (OR = 3.6) (95% IC 1.0-12.0). Infants who were symptomatic at birth showed a probability of MRI brain lesions 3.2 times higher than those who were asymptomatic. Ten out of 17 (59%) children who were asymptomatic at birth showed MRI-WM alterations or ventriculomegaly. CONCLUSIONS: Brain MRI abnormalities, such as WM alterations and ventriculomegaly, expressed as MRI score higher than 2 are associated with an increased probability of long-term adverse neurological outcome in congenitally CMV infected infants, symptomatic and asymptomatic at birth.

Cutaneous Infantile Haemangiomas with Intracranial and Intraspinal Involvement: A European Multicentre Experience and Review.

Infantile haemangiomas are very common benign tumours in the first months of life. They are mostly cutaneous; however, extracutaneous lesions are possible, and occur in very rare cases in the central nervous system. A European multicentre observational retrospective study was conducted in the last 5 years. Seven patients with intracranial or intraspinal infantile haemangiomas were selected and treated with oral propranolol. Propranolol was interrupted after complete or almost complete resolution of infantile haemangiomas. All patients tolerated the treatment well without side-effects. Central nervous system infantile haemangiomas are probably underestimated due to the frequent absence of symptoms and their spontaneous involution. However, they should be investigated in case of segmental cutaneous infantile haemangiomas, particularly on the head, neck, upper trunk, lumbar or sacral area in order to diagnosis intra-central nervous system involvement at an early stage.

T-cell depleted HLA-haploidentical HSCT in a child with neuromyelitis optica.

Neuromyelitis optica is an immune-mediated disease characterized by a relapsing course, resulting in progressive disability. In children, given the long life expectancy, a disease-modifying treatment could be particularly desirable. Unfortunately, the currently available treatment strategies with this potential are scarce. Very limited data are available about the use of allogeneic hematopoietic stem cell transplantation (HSCT) for autoimmune neurological diseases. In this report, we present a pediatric case successfully treated with allogeneic HSCT from an HLA-haploidentical donor, after ex vivo TCR/CD19-depletion of the graft. To the best of our knowledge, this is the first case of a pediatric patient to benefit from such a treatment.

HHV6-related mild encephalopathy with reversible splenial lesion (MERS) presenting with urinary and fecal retention in an Italian adolescent.

Mild encephalopathy with a reversible splenial lesion (MERS) is an uncommon clinico-radiological entity characterized by magnetic resonance imaging (MRI) findings of a reversible lesion in the splenium of corpus callosum associated with a significant neurological manifestation of encephalopathy. The majority of reported cases involve the Asiatic population and are closely associated with infection. We report the case of an adolescent with an HHV6-related MERS presenting with hyponatremia and urinary and fecal retention. To our knowledge, urinary retention is not a constant aspect of the disease and has rarely been described, while fecal retention has never been reported before. Despite the self-limiting nature of the disease, it is mandatory to suspect it for a faster diagnosis and it might be useful to know its rare occurrences in order to better understand its etiopathogenetic mechanisms.

Asymmetric cavernous sinus enlargement: a novel finding in Sturge-Weber syndrome.

PURPOSE: Enlargement of deep cerebral veins and choroid plexus engorgement are frequently reported in Sturge-Weber syndrome. We aim to describe cavernous sinus involvement in patients with this syndrome and to identify possible clinical-neuroimaging correlations. METHODS: Sixty patients with Sturge-Weber syndrome (31 females, mean age 4.5 years) and 120 age/sex-matched controls were included in this retrospective study. We performed a visual analysis to identify patients with asymmetric cavernous sinus enlargement. Then, we measured on axial T2WI the left (A), right (B), and bilateral (LL) transverse diameters of the cavernous sinus. We calculated the module of the difference |A-B| and the cavernous sinus asymmetry index as the ratio |A-B|/LL. Differences among groups were assessed by Mann-Whitney U and Kruskal-Wallis tests. Clinicoradiological associations were evaluated by Fisher exact test. RESULTS: We found seven subjects (11.6%) with asymmetric CS enlargement. The |A-B| and cavernous sinus asymmetry index were higher in patients with asymmetric CS enlargement compared with controls and patients without visible CS abnormalities (pB < 0.05). Asymmetric CS enlargement was always ipsilateral to facial port-wine stains (7/7), and, when present, to leptomeningeal vascular malformations (4/7). It was significantly associated with ipsilateral bone marrow changes (p = 0.013) and dilated veins (p = 0.002). Together with brain atrophy and deep venous dilatation, this sign was associated with neurological deficits (p < 0.05). CONCLUSIONS: We expanded the spectrum of venous abnormalities in SWS, showing the presence of asymmetric cavernous sinus enlargement in more than one tenth of patients, likely related to increased venous drainage.

Predictors of Evolution Into Multiple Sclerosis After a First Acute Demyelinating Syndrome in Children and Adolescents.

Background/Objective: The aim of the study was to estimate the rate of evolution or for multiple sclerosis (MS), after a first acute demyelinating event (ADE) in pediatric patients, and to investigate the variables that predict this evolution. Methods: We retrospectively evaluated the clinical and neuroradiological features of children who presented a first ADE between January 2005 and April 2017. All patients included underwent a baseline MRI, a cerebrospinal fluid and blood analysis, including virological examinations. The evolution into MS was determined by the 2013 International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria. Clinical and radiological features predictive of MS were determined using multivariate analyses. Results: Ninety-one patients were selected (mean age at onset: 10.11 ± 4.6). After a mean follow-up of 5.6 ± 2.3 years, 35% of patients' conditions evolved to MS. In the logistic multivariate analysis of clinical and laboratory data, the best predictors of evolution into MS were: the presence of oligoclonal bands in CSF (p < 0.001), past infection with EBV (p < 0.001), periventricular lesions (p < 0.001), hypointense lesions on T1 (p < 0.001), and lesions of the corpus callosum (p < 0.001) including Dawson fingers (p < 0.001). Conclusion: Our findings suggest that a pattern of neuroimaging and laboratory findings may help to distinguish between, at clinical onset, children with a monophasic syndrome (clinically isolated syndrome or acute disseminated encephalomyelitis) from those who will develop MS.