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.

Reliability on multiband diffusion NODDI models: A test retest study on children and adults.

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.

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.

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.

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.

Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children.

BACKGROUND: Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. OBJECTIVE: The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. MATERIALS AND METHODS: This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naïve patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. RESULTS: A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). CONCLUSION: Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children.

White matter disruption is associated with persistent seizures in tuberous sclerosis complex.

BACKGROUND AND AIMS: White matter is diffusely altered in tuberous sclerosis complex (TSC), and these alterations appear to be more evident in subjects with a more severe neurologic phenotype. However, little is known on the correlation between white matter alterations and epilepsy in TSC. The aims of this study were to evaluate the effects of early onset and refractory seizures on white matter by using diffusion tensor imaging (DTI). METHODS: We enrolled 20 children with TSC and epilepsy onset in the first 3years of life and grouped them according to seizure persistence or freedom. All patients underwent brain MRI with DTI. Specific ROIs have were placed to generate tracks to calculate fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Statistical analysis was performed by ANOVA. RESULTS: Children with persistent seizures presented an overall reduced FA, with statistically significant differences on the cingulum (right p=0.003, left p=0.016), the left cerebral peduncle (p=0.020), the superior cerebellar peduncles (right p=0.008, left p=0.002), the posterior limbs of internal capsule (right p=0.037, left p=0.015), the external capsule (right p=0.018, left p=0.031), the inferior frontooccipital fasciculus (right p=0.010, left p=0.026), and the temporal trunk (right p=0.017, left p=0.001). CONCLUSIONS: Our study demonstrated that children with persistent seizures present more significant alterations of brain connectivity in areas crucial for global cognitive maturation, executive functions, and verbal abilities, implying a higher risk of cognitive impairment, attention-deficit hyperactivity disorder, and autism.

Cerebral sinovenous thrombosis (CSVT) in children: what the pediatric radiologists need to know.

Cerebral sinovenous thrombosis (CSVT) is a relatively uncommon and potentially life-threatening condition in childhood, occurring in various clinical settings. Nowadays, however, it is increasingly diagnosed as related to many causes, likely due to greater clinical awareness and improvement of neuroradiologic techniques. The prompt diagnosis is an important goal to significantly reduce the risk of acute complications and long-term sequelae. The purpose of this narrative overview is to provide a useful educational tool in daily clinical practice for radiologists with a broad perspective of CSVT including a discussion of more common potential pitfalls related to misinterpretation of images in children. This paper will also review the normal venous anatomy, its variants, risk factors that contribute to cause CSVT (neonates with their specific causes of CSVT are not included in this review) and the practical imaging feature of cerebral sinovenous thrombosis on MRI and CT. Finally, a brief overview of frequent and severe CSVT conditions in children with key points in imaging is shown.

Spinal ependymoma in a patient with Kabuki syndrome: a case report.

BACKGROUND: Kabuki syndrome is a rare disorder characterized by the association of mental retardation and postnatal growth deficiency with distinctive facial appearance, skeletal anomalies, cardiac and renal malformation. Two causative genes have been identified in patients with Kabuki syndrome. Mutation of KMT2D (MLL2) was identified in 55-80% of patients, while 9-14% of KMT2D negative patients have mutation in KDM6A gene. So far, few tumors have been reported in patients with Kabuki syndrome. We describe the first case of a patient with spinal ependymoma and Kabuki syndrome. CASE PRESENTATION: A 23 years old girl followed at our Center for KMT2D mutated Kabuki syndrome since she was 4 years old presented with acute lumbar pain and intermittent tactile hyposthenia of the feet. Spine magnetic resonance revealed a lumbar endocanalar mass. She underwent surgical resection of the lesion and histologic examination showed a tanycytic ependymoma (WHO grade II). CONCLUSION: Kabuki syndrome is not considered a cancer predisposition syndrome. Nonetheless, a number of tumors have been reported in patients with Kabuki syndrome. Spinal ependymoma is a rare disease in the pediatric and young adult population. Whereas NF2 mutations are frequently associated to ependymoma such an association has never been described in Kabuki syndrome. To our knowledge this is the first case of ependymoma in a KMT2D mutated Kabuki syndrome patient. Despite KMT2D role in cancer has previously been described, no genetic data are available for previously reported Kabuki syndrome patients with tumors. Nonetheless, the association of two rare diseases raises the suspicion for a common determinant.

Atypical teratoid/rhabdoid tumor (ATRT) arising from the 3rd cranial nerve in infants: a clinical-radiological entity?

Atypical teratoid/rhabdoid tumor (ATRT) is a rare embryonal tumor of the central nervous system with preponderance in very young children, the majority of whom are younger than 3 years of age at diagnosis. Historically, outcomes of this aggressive disease, even with extensive multimodal therapy, have been dismal. Recent improvements have come from therapies directed exclusively towards ATRT, but misdiagnosis or delays in the correct diagnosis lead to significantly worse survival rates. ATRTs most commonly occur supratentorially but have been described in virtually all central nervous system locations, including the cerebellopontine angle cistern, meninges, and spinal canal, and extradural locations. ATRTs originating from cranial nerves are rare. Here, we describe three cases of solitary ATRT arising from the 3rd cranial nerve (CN III) or close to its origin in the midbrain, all of which presented in patients within 6 months of birth, with isolated unilateral oculomotor nerve palsy and strikingly similar magnetic resonance imaging (MRI) features. These MRI features include IV contrast enhancement, relative T2 hyposignal, and restricted water diffusion on apparent diffusion coefficient images, findings which are consistent with angiogenesis and high cellularity, and hence, suggestive of malignancy. We conclude that ATRT should be placed high on the differential diagnosis list when encountering a young infant presenting with isolated, unilateral 3rd nerve palsy and a small, solitary tumor arising from CN III that demonstrates malignant conventional and diffusion-weighted imaging features on MRI.

Response of recurrent BRAFV600E mutated ganglioglioma to Vemurafenib as single agent.

BACKGROUND: Ganglioglioma (GG) and pilocytic astrocytoma (PA) represent the most frequent low-grade gliomas (LGG) occurring in paediatric age. LGGs not amenable of complete resection (CR) represent a challenging subgroup where traditional treatments often fail. Activation of the MAP Kinase (MAPK) pathway caused by the BRAFV600E mutation or the KIAA1549-BRAF fusion has been reported in pediatric GG and PA, respectively. CASE PRESENTATION: We report on a case of BRAFV600E mutated cervicomedullary GG treated with standard chemotherapy and surgery. After multiple relapse, BRAF status was analyzed by immunohistochemistry and sequencing showing a BRAFV600E mutation. Treatment with Vemurafenib as single agent was started. For the first time, a radiological and clinical response was obtained after 3 months of treatment and sustained after 6 months. CONCLUSION: Our experience underline the importance of understanding the driver molecular alterations of LGG and suggests a role for Vemurafenib in the treatment of pediatric GG not amenable of complete surgical resection.

Statistical inference with a manifold-constrained RNA velocity model uncovers cell cycle speed modulations.

Across a range of biological processes, cells undergo coordinated changes in gene expression, resulting in transcriptome dynamics that unfold within a low-dimensional manifold. Single-cell RNA-sequencing (scRNA-seq) only measures temporal snapshots of gene expression. However, information on the underlying low-dimensional dynamics can be extracted using RNA velocity, which models unspliced and spliced RNA abundances to estimate the rate of change of gene expression. Available RNA velocity algorithms can be fragile and rely on heuristics that lack statistical control. Moreover, the estimated vector field is not dynamically consistent with the traversed gene expression manifold. Here, we develop a generative model of RNA velocity and a Bayesian inference approach that solves these problems. Our model couples velocity field and manifold estimation in a reformulated, unified framework, so as to coherently identify the parameters of an autonomous dynamical system. Focusing on the cell cycle, we implemented VeloCycle to study gene regulation dynamics on one-dimensional periodic manifolds and validated using live-imaging its ability to infer actual cell cycle periods. We benchmarked RNA velocity inference with sensitivity analyses and demonstrated one- and multiple-sample testing. We also conducted Markov chain Monte Carlo inference on the model, uncovering key relationships between gene-specific kinetics and our gene-independent velocity estimate. Finally, we applied VeloCycle to in vivo samples and in vitro genome-wide Perturb-seq, revealing regionally-defined proliferation modes in neural progenitors and the effect of gene knockdowns on cell cycle speed. Ultimately, VeloCycle expands the scRNA-seq analysis toolkit with a modular and statistically rigorous RNA velocity inference framework.

Sex-dimorphic and age-dependent organization of 24-hour gene expression rhythms in humans.

The circadian clock modulates human physiology. However, the organization of tissue-specific gene expression rhythms and how these depend on age and sex is not defined in humans. We combined data from the Genotype-Tissue Expression (GTEx) project with an algorithm that assigns circadian phases to 914 donors, by integrating temporal information from multiple tissues in each individual, to identify messenger RNA (mRNA) rhythms in 46 tissues. Clock transcripts showed conserved timing relationships and tight synchrony across the body. mRNA rhythms varied in breadth, covering global and tissue-specific functions, including metabolic pathways and systemic responses. The clock structure was conserved across sexes and age groups. However, overall gene expression rhythms were highly sex-dimorphic and more sustained in females. Rhythmic programs generally dampened with age across the body.

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.

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.

Assessing cortical features in early stage ASD children.

Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental disorder largely investigated in the neurologic field. Recently, neuroimaging studies have been conducted in order to investigate cerebral morphologic alterations in ASD patients, demonstrating an atypical brain development before the clinical manifestations of the disorder. Cortical Thickness (CT) and Local Gyrification Index (LGI) distribution for ASD children were investigated in this study, with the aim to evaluate possible relationship between brain measures and individual characteristics (i.e., IQ and verbal ability). 3D T1-w sequences from 129 ASD and 58 age-matched Healthy Controls (HC) were acquired and processed in order to assess CT and LGI for each subject. Intergroup differences between ASD and HC were investigated, including analyses of 2 ASD subgroups, split according to patient verbal ability and IQ. When compared to HC, ASD showed increased CT and LGI within several brain areas, both as an overall group and as verbal ability an IQ subgroups. Moreover, when comparing language characteristics of the ASD subjects, those patients with verbal ability exhibit significant CT and LGI increase was found within the occipital lobe of right hemisphere. No significant results occurred when comparing ASD patients according to their IQ value. These results support the hypothesis of abnormal brain maturation in ASD since early childhood with differences among clinical subgroups suggesting different anatomical substrates underlying an aberrant connectivity.

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.

Hemimegalencephaly associated with congenital infiltrating lipomatosis of the face: a case report.

Hemimegalencephaly (HME) is a rare congenital malformation of the brain, grossly characterized by enlargement and overdevelopment of one cerebral hemisphere. We describe a 16-month-old patient with facial asymmetry caused by congenital infiltrating lipomatosis of the face (CILF) associated with ipsilateral HME. Although HME has been described as part of different syndromic diseases, the association of HME with CILF has been rarely reported. Our case and literature review suggest that when the diagnosis of CILF is suspected or established, the possible presence of associated HME has to be considered and a magnetic resonance imaging (MRI) must be performed even in absence of neurological features, not always present in early stages. MRI also demonstrates the involvement of intracranial structures outside the affected cerebral hemisphere, such as brain stem, cerebellum, cranial nerves, and blood vessels. In our patient, computed tomography of the brain provided detailed information on osseous hypertrophy and skull-base foramina enlargement.