Kshitij Mankad

• Great Ormond Street Hospital for Children NHS Foundation Trust

Hypermanganesaemia with Dystonia 1 and 2 (HMNDYT1 and 2) are inherited, autosomal recessive disorders caused by pathogenic variants in the genes encoding the manganese transporters SLC30A10 and SLC39A14, respectively. Impaired hepatic and enterocytic manganese uptake (SLC39A14) and excretion (SLC30A10) lead to deposition of manganese in the basal g...

Background Craniopharyngioma (CP) account for 80% of childhood hypothalamo-pituitary tumors and, though benign, their proximity to the visual pathways, hypothalamus, and pituitary incurs significant long-term neurologic and endocrine morbidity. Informed surgical decision-making has the potential to reduce morbidity and improve outcomes. There remai...

Background Paediatric brain tumour survivors can have neurocognitive deficits that negatively impact their quality of life, but it is unclear if deficits are primarily caused by treatments, such as radiotherapy, or manifest earlier due to the tumour and related complications. The aim of this work is to characterise white matter injury caused by bra...

Importance A leading cause of surgically remediable, drug-resistant focal epilepsy is focal cortical dysplasia (FCD). FCD is challenging to visualize and often considered magnetic resonance imaging (MRI) negative. Existing automated methods for FCD detection are limited by high numbers of false-positive predictions, hampering their clinical utility...

Neuroimaging investigations are fundamental in the diagnosis of patients with epilepsy. The International League Against Epilepsy (ILAE) harmonized neuroimaging of epilepsy structural sequences (HARNESS‐MRI) protocol was intended as a generalizable structural MRI protocol. The European Reference Network for Rare and Complex Epilepsies, EpiCARE, inc...

We describe a set of monozygotic twins with GRIN2B-related neurodevelopmental disorder (GRIN2B-ND) who exhibited distinct clinical and imaging characteristics due to a de novo heterozygous pathogenic variant in the GRIN2B gene (c.2453T>C, p.Met818Thr). Twin A displayed extensive symmetric malformation of cortical development (MCD) resembling polymi...

Background: Paediatric brain tumour survivors can have neurocognitive deficits that negatively impact their quality of life, but it is unclear if deficits are primarily caused by treatments, such as radiotherapy, or manifest earlier due to the tumour and related complications. The aim of this work is to characterise white matter injury caused by br...

Distinguishing tumours from other conditions is a primary challenge in paediatric neuro-radiology. This paper aims to describe mimics, which are non-neoplastic conditions that have features similar to a neoplastic process caused by a non-neoplastic entity, and chameleons, which are uncommon presentations of brain tumours that are mistaken for other...

Objective Hippocampal sclerosis (HS), the most common pathology associated with temporal lobe epilepsy (TLE), is not always visible on magnetic resonance imaging (MRI), causing surgical delays and reduced postsurgical seizure‐freedom. We developed an open‐source software to characterize and localize HS to aid the presurgical evaluation of children...

The rate of discovery and increased understanding of genetic causes for neurodevelopmental disorders has peaked over the past decade. It is well recognised that some genes show marked variability in neuroradiological phenotypes, and inversely, some radiological phenotypes are associated with several different genetic conditions. However, some readi...

The Response Assessment in Pediatric Neuro-Oncology (RAPNO) Working Group is an international, collaborative network of experts dedicated to pediatric central nervous system (CNS) tumors that was created in 2011. Since then, six RAPNO articles with imaging guidelines for response assessment in diverse pediatric tumor subgroups have been published,...

Background Malformations of cortical development (MCDs) in children with focal epilepsy pose significant diagnostic challenges, and a precise radiological diagnosis is crucial for surgical planning. New MRI sequences and the use of artificial intelligence (AI) algorithms are considered very promising in this regard, yet studies evaluating the relat...

Background and objectives: Antibodies to myelin oligodendrocyte glycoprotein (MOG-Ab) have recently been reported in patients with encephalitis who do not fulfill criteria for acute disseminated encephalomyelitis (ADEM). We evaluated a cohort of these children and compared them with children with ADEM. Methods: This retrospective, multicenter co...

Purpose Normative ADC values of the pineal gland in young children are currently lacking, however, these are potentially useful in the differential diagnosis of pineal involvement in trilateral retinoblastoma, which is challenging when the size of the tumor is less than 10–15 mm. The main objective of this study was to establish ADC reference value...

OBJECTIVE Intraoperative magnetic resonance imaging (iMRI) use is becoming increasingly widespread in neurosurgical practice, and most of the data reporting its use are in adult populations. There is less evidence on the use of iMRI in pediatric neurosurgery. The aim of this paper was to synthesize the available literature into a systematic review...

The goal of this paper is to provide a useful desktop reference for the imaging of suspected child abuse with clear, age-specific pathways for appropriate evidence-based imaging and follow-up. We aim to provide a road map for the imaging evaluation and follow-up of this important and vulnerable cohort of patients presenting with signs and symptoms...

While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric pos...

Cortically based brain tumors in children constitute a unique set of tumors with variably aggressive biologic behavior. Because radiologists play an integral role on the multidisciplinary medical team, a clinically useful and easy-to-follow flow chart for the differential diagnoses of these complex brain tumors is essential. This proposed algorithm...

Background Central nervous system (CNS) cancers are a leading cause of childhood cancer-related mortality. Accurate staging and assessment of leptomeningeal spread, particularly in aggressive neoplasms like embryonal tumors, is crucial for treatment planning and prognosis. Conventional diagnostic methods, relying on MRI and CSF cytology, have limit...

Inherited disorders of neurotransmitter metabolism comprise an expanding heterogeneous spectrum of diseases associated with complex movement disorders, autonomic features, and global developmental delay (GDD).1, 2 Monoamine neurotransmitter disorders (NTD) are due to primary or secondary defects in the biosynthesis, degradation or transport of dopa...

Brain malformations represent a heterogeneous group of abnormalities of neural morphogenesis, often associated with aberrations of neuronal connectivity and brain volume. Prenatal detection of brain malformations requires a clear understanding of embryology and developmental morphology through the various stages of gestation. This expert panel revi...

Background Intracranial birth-related subdural hemorrhage frequently occurs in asymptomatic newborns and has no adverse long-term sequelae. It is medically and medicolegally important to differentiate birth-related subdural hemorrhage from other pathological causes of intracranial hemorrhage. There is limited literature available on the incidence o...

The post-transcriptional modification of tRNAs plays a key role in tRNA folding and function to ensure proper levels of protein synthesis during growth and development. Pathogenic variants in tRNA modification enzymes have been implicated in diverse human neurodevelopmental and neurological disorders. However, the molecular basis for many of these...

Aims The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro‐oncology speciality. Method...

Background and purpose: Neuronal ceroid lipofuscinoses (NCL) are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for CLN2, a subtype of NCL. The aim of this study was to quantify brain volume loss in CLN2 disease of patients on ERT in comparison to a natural history cohort using magnetic resonance im...

The differential diagnosis of supratentorial brain tumours in children can be challenging, especially considering the recent changes to the WHO classification of CNS tumours published in 2021. Many new tumour types have been proposed which frequently present in children and young adults and their imaging features are currently being described by th...

We aimed to investigate the potential added value of postmortem MRI (PMMRI) in sudden unexpected infant death (SUID) cases referred to our center between September 2020 and June 2023. Ultimately, 19 SUID cases underwent PMMRI alongside standard autopsy procedures, which included technical examinations such as postmortem CT (PMCT). Four radiologists...

BACKGROUND Over half of childhood brain tumours originate in the posterior fossa, which includes low-grade (e.g. pilocytic astrocytoma) and high-grade (e.g. medulloblastoma) tumours. Even though overall survival rates of paediatric brain tumours have substantially increased, survivors face neuropsychological impairments impacting behaviour, cogniti...

BACKGROUND Craniopharyngioma (CP) account for 80% of childhood hypothalamopituitary tumours and, though benign, their proximity to the visual pathways, hypothalamus, and pituitary incurs significant long-term neurologic and endocrine morbidity. Informed surgical decision-making has the potential to reduce morbidity and improve outcomes. METHODS Th...

BACKGROUND Craniopharyngioma are heterogeneous hypothalamopituitary tumours with solid and cystic components which have a distinct natural history. Neuroimaging follow-up and the definition of progressive disease is challenging due to unpredictable growth of the inflammatory cystic component. METHODS This multicentre retrospective observational st...

BACKGROUND Gliomas form bidirectional, functional synapses with otherwise healthy neurons: increasing neuronal excitability and driving tumour growth. The prognostic significance of this phenomenon does, however, remain unknown. METHODS This study used tumour location and tumour network mapping to identify brain networks associated with tumour pro...

Background and objectives: To test the performance of the 2023 myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) criteria in adults and children with inflammatory demyelinating conditions who were tested for MOG antibodies (Abs). Methods: This was a retrospective study of patients tested for MOG-Abs from 2018 to 2022 in 2 spe...

Aim Sturge–Weber syndrome (SWS) is a rare neurocutaneous syndrome, frequently associated with pharmaco‐resistant, early‐onset epilepsy. Optimal seizure control is paramount to maximize neurodevelopment. Method A single‐centre case series of 49 infants explored early SWS care. Ninety‐two per cent of children developed seizures aged 0 to 3 years; 55...

Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor group. The natural history, when curative resection is not possible, is one of a chronic disease with periods of tumor stability and episodes of tumor progression. While there is a high overall survival rate, many patients experience significant and potentially lifelong morb...

Purpose Morning glory disc anomaly (MGDA) is a rare congenital ophthalmologic disorder. Historically it has been diagnosed fundoscopically, with little in the literature regarding its imaging findings. The purpose of this study is to further characterize the orbital and associated intracranial magnetic resonance imaging (MRI) findings of MGDA in ou...

Background and objectives: Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum d...

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without considerati...

This study reports on biallelic homozygous and monoallelic de novo variants in SLITRK3 in three unrelated families presenting with epileptic encephalopathy associated with a broad neurological involvement characterized by microcephaly, intellectual disability, seizures, and global developmental delay. SLITRK3 encodes for a transmembrane protein tha...

Dysraphic malformations of the spine and spinal cord (DMSSC) represent a spectrum of common congenital anomalies typically (though not exclusively) affecting the lower spinal segments. These may be responsible for varying degrees of neurologic, orthopedic, and urologic morbidity. With advances in neuroimaging, it is now possible to better diagnose...

Gadolinium-based contrast agents (GBCAs) form the cornerstone of current primary brain tumor MRI protocols at all stages of the patient journey. Though an imperfect measure of tumor grade, GBCAs are repeatedly used for diagnosis and monitoring. In practice, however, radiologists will encounter situations where GBCA injection is not needed or of dou...

Purpose Nasal chondromesenchymal hamartomas (NCMH) are rare, predominantly benign tumors of the sinonasal tract. The distinction from higher grade malignancy may be challenging based on imaging features alone. To increase the awareness of this entity among radiologists, we present a multi-institutional case series of pediatric NCMH patients showing...

We present a case of primary rhabdoid tumour of the orbit. Presenting features at birth included congenital ptosis, conjunctival injection, hyphaema and microphthalmia. The unique presentation caused a late diagnosis following the development of rapid proptosis 6 months later. We suggest that orbital rhabdoid tumour be considered in the differentia...

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carry...

Cardiofaciocutaneous (CFC) syndrome is one of the rarest RASopathies characterized by multiple congenital ectodermal, cardiac and craniofacial abnormalities with a mild to severe ocular, gastrointestinal and neurological involvement. It is an autosomal dominant syndrome, with complete penetrance, caused by heterozygous pathogenic variants in the ge...

Background Lesion resolution is often observed in children with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and asymptomatic lesions are less commonly reported in MOGAD than in multiple sclerosis (MS). Objective We aimed to evaluate brain MRI changes over time in paediatric MOGAD. Methods Retrospective study in eight...

Head trauma is one of the leading causes of visits to the emergency department. Infant skull fracture thresholds and patterns can be different from those in older children because they are comprised of thin, flexible bones with unfused sutures and have greater capacity for moulding and transmis- sion of impact forces. Here, we examine whether singl...

Hippocampal Sclerosis (HS) can elude visual detection on MRI scans of patients with temporal lobe epilepsy (TLE), causing delays in surgical treatment and reducing the likelihood of postsurgical seizure-freedom. We developed an open-source software that (1) detects HS from structural MRI scans, (2) generalises across a heterogeneous multicentre coh...

We describe a novel, severe autoinflammatory syndrome characterized by neuroinflammation, systemic autoinflammation, splenomegaly, and anemia (NASA) caused by bi-allelic mutations in IRAK4. IRAK-4 is a serine/threonine kinase with a pivotal role in innate immune signaling from toll-like receptors and production of pro-inflammatory cytokines. In hum...

Aim This study aimed to (1) quantify attention and executive functioning in children with developmental coordination disorder (DCD), (2) assess whether some children with DCD are more likely to show attention difficulties, and (3) characterize brain correlates of motor and attention deficits. Method Fifty‐three children (36 with DCD and 17 without...

BACKGROUND AND PURPOSE: Although cardinal imaging features for the diagnostic criteria of the Dandy-Walker phenotype have been recently defined, there is a large range of unreported malformations among these patients. The brainstem, in particular, deserves careful attention because malformations in this region have potentially important implication...

Background and purpose: Prior studies have found an association between calcification and the epileptogenicity of tubers in tuberous sclerosis complex. Quantitative susceptibility mapping is a novel tool sensitive to magnetic susceptibility alterations due to tissue calcification. We assessed the utility of quantitative susceptibility mapping in i...

Laser ablation for treatment of hypothalamic hamartoma (HH) is a minimally invasive and effective technique used to destroy hamartomatous tissue and disconnect it from the functioning brain. Currently, the gold standard to evaluate the amount of tissue being “burned” is the use of heat maps during the ablation procedure. However, these maps have lo...

Background Atypical or complex paediatric neurological presentations are common clinical conundrums and often remain undiagnosed despite extensive investigations. This is particularly pronounced in immunocompromised patients. Here we show that clinical metagenomics (CMg) is a valuable adjunct diagnostic tool to be used by neuro-infection multidisci...

We report two children with molecularly confirmed mitochondrial disease mimicking Neuromyelitis Optica Spectrum Disorder (NMOSD). The first patient presented at the age of 15 months with acute deterioration following a pyrexial illness with clinical features localising to the brainstem and spinal cord. The second patient presented at 5 years with a...

Background Radiomics is the process of converting radiological images into high-dimensional data that may be used to cre- ate machine learning models capable of predicting clinical outcomes, such as disease progression, treatment response and survival. Pediatric central nervous system (CNS) tumors differ from adult CNS tumors in terms of their tiss...

Congenital melanocytic naevus (CMN) syndrome, previously termed neurocutaneous melanosis, is a rare disease caused by postzygotic mosaic mutations occurring during embryogenesis in precursors of melanocytes. The severity of neurological manifestations in CMN patients is related to central nervous system abnormalities found at magnetic resonance ima...

Objective: Birk-Landau-Perez syndrome is a genetic disorder caused by biallelic pathogenic variants in SLC30A9 presenting with a complex movement disorder, developmental regression, oculomotor abnormalities and renal impairment. So far it has been reported in only two families. We describe the clinical phenotype of eight further individuals from f...

This pictorial review provides an algorithmic approach and framework for systematic diagnostic evaluation of the fetus with intrauterine/fetal MRI (iuMRI) failed visualization of the cavum septum pellucidum (CSP) flanked by the septal leaflets (SLs) at the mid-trimester ultrasound. Pitfalls in sonographic diagnosis of normal or abnormal CSP/SLs, iu...

This second roundtable discussion was convened at the 56th European Society of Paediatric Radiology (ESPR) 2022 Annual Meeting in Marseille, France, to discuss controversial aspects of imaging in child abuse. The following topics were discussed:Fracture dating—the published literature is broadly similar with respect to the identification of the rad...

Importance: Physical abuse is a common but preventable cause of long-term childhood morbidity and mortality. Despite the strong association between abuse in an index child and abuse in contact children, there is no guidance outlining how to screen the latter, significantly more vulnerable group, for abusive injuries. Consequently, the radiological...

In infants without a history of trauma, subdural haemorrhages should raise the concern for an abusive head injury, particularly when they are associated with bridging vein clotting/rupture or with septations. However, non-haemorrhagic, fluid-appearing subdural collections (also called hygromas) may also be the result of abuse. Subdural collections...

Aims: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standa...

Abusive head trauma is not a radiological diagnosis and is made following assessment by a multidisciplinary team comprising various specialties such as physicians, surgeons, radiologists, social workers, and child protection services. The radiologist often plays the role of “sentinel” expert in raising the possibility of abusive head trauma (AHT),...

Purpose Atypical teratoid/rhabdoid tumours (ATRTs) are malignant embryonal tumours of childhood that affect the central nervous system (CNS). We aim to determine which factors, including patient age, extent of resection (EOR), presence of distal metastasis and use of adjuvant therapies, affect overall survival in children with atypical teratoid/rha...

Biotinidase deficiency is an autosomal recessive condition caused by pathogenic variants in the BTD gene. Resultant deficiency of free biotin leads to impaired activity of the enzyme carboxylase and related neurologic, dermatologic, and ocular symptoms. Many of these are reversible on treatment, but early recognition and commencement of biotin supp...

Purpose This study assessed the position of the termination of the conus medullaris (the point where the spinal cord tapers to an end) and thecal sac (the sheath of dura mater that surrounds the spinal cord and caudal nerve roots) in a large pediatric population, to characterise the nature of the pediatric Gaussian distribution and assess whether a...

Purpose To report an unexpectedly asymmetric, progressive nutritional optic neuropathy associated with vitamin A deficient optic canal hyperostosis in a 15-year-old female with a long history of a restricted diet. Methods We performed comprehensive ophthalmic assessments in a fifteen-year-old female with a long history of restricted eating who pre...

Background and Objective Epilepsy affects approximately 50 million people worldwide, with 30–40% of patients not responding to medication, necessitating alternative therapies such as surgical intervention. However, the accurate localization of epileptogenic lesions, particularly in pediatric magnetic resonance imaging (MRI)-negative drug-resistant...

Background MAPK-activated protein kinase 5 (MAPKAPK5) is an essential enzyme for diverse cellular processes. Dysregulation of the pathways regulated by MAPKAPK enzymes can lead to the development of variable diseases. Recently, homozygous loss-of-function variants in MAPKAPK5 were reported in four patients from three families presenting with a reco...

We report on biallelic homozygous and monoallelic de-novo variants in SLITRK3 in 3 unrelated families presenting with epileptic encephalopathy associated with a broad neurological involvement characterized by microcephaly, intellectual disability, seizures, and global developmental delay. SLITRK3 encodes for a transmembrane protein that is involved...

Background and purpose: β propeller protein-associated neurodegeneration (BPAN) is the most common neurodegeneration with brain iron accumulation disorder. Typical radiologic findings are T2 hypointensity in the substantia nigra and globus pallidus, as well as a T1 halolike substantia nigra hyperintense signal surrounding a hypointense central are...