Kshitij Mankad

Great Ormond Street Hospital for Children NHS Foundation Trust | GOSH · Department of Radiology

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...

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...

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...

Background and purpose: The traditionally described Dandy-Walker malformation comprises a range of cerebellar and posterior fossa abnormalities with variable clinical severity. We aimed to establish updated imaging criteria for Dandy-Walker malformation on the basis of cerebellar development. Materials and methods: In this multicenter study, ret...

Background and purpose: The 5th edition of the World Health Organization Classification of CNS tumors defines the CNS neuroblastoma FOXR2 in the group of embryonal tumors. Published clinical outcomes tend to suggest a favorable outcome after resection, craniospinal irradiation, and chemotherapy. This multicenter study aimed to describe imaging fea...

Background and purpose: Pediatric posterior fossa tumors often present with hydrocephalus; postoperatively, up to 25% of patients develop cerebellar mutism syndrome. Arterial spin-labeling is a noninvasive means of quantifying CBF and bolus arrival time. The aim of this study was to investigate how changes in perfusion metrics in children with pos...

Purpose: The aim of the study was to assess the prevalence and characteristics of spinal cord cavernous malformations (SCCM) and intraosseous spinal vascular malformations (ISVM) in a pediatric familial cerebral cavernous malformation (FCCM) cohort and evaluate clinico-radiological differences between children with (SCCM +) and without (SCCM-) SCC...

Background/aims: Optic pathway gliomas (OPGs) may cause progressive visual loss despite chemotherapy. Newer, less toxic treatments might be given earlier, depending on visual prognosis. We aimed to investigate the prognostic value of visual evoked potentials (VEP) and optical coherence tomography (OCT). Methods: A retrospective study of OPG pati...

Introduction Apert syndrome is an autosomal dominant malformation syndrome, accounting for 4.5% of all craniosynostoses. Raised intracranial pressure (ICP) in Apert syndrome has a multifactorial aetiology, with an incidence of up to 45% if left untreated [1, 2]. Raised ICP can be determined clinically, with non-invasive and invasive methods. In thi...

The genetic interferonopathies are a heterogeneous group of disorders thought to be caused by the dysregulated expression of interferons and are now commonly considered in the differential diagnosis of children presenting with recurrent or persistent inflammatory phenotypes. With emerging therapeutic options, recognition of these disorders is incre...

Background and purpose: Pathogenic variants in the ACTA2 gene cause a distinctive arterial phenotype that has recently been described to be associated with brain malformation. Our objective was to further characterize gyral abnormalities in patients with ACTA2 pathogenic variants as per the 2020 consensus recommendations for the definition and cla...

Background and purpose: Neuroimaging has an important role in detecting CNS involvement in children with systemic or CNS isolated hemophagocytic lymphohistiocytosis. We characterized a cohort of pediatric patients with CNS hemophagocytic lymphohistiocytosis focusing on neuroradiologic features and assessed whether distinct MR imaging patterns and...

The 2015 Magnetic Resonance Imaging in Multiple Sclerosis and 2016 Consortium of Multiple Sclerosis Centres guidelines on the use of MRI in diagnosis and monitoring of multiple sclerosis made an important step towards appropriate use of MRI in routine clinical practice. Since their promulgation, there have been substantial relevant advances in know...

PurposeTo describe the trans-occipital asymmetries of pattern and flash visual evoked potentials (VEPs), in an infant with MRI findings of unilateral optic nerve aplasia and hemi-chiasm dysplasia.MethodsA child with suspected left cystic microphthalmia, left microcornea, left unilateral optic nerve aplasia, and hemi-chiasm underwent a multi-channel...

Background and purpose: Primary posterior fossa tumors comprise a large group of neoplasias with variable aggressiveness and short and long-term outcomes. This study aimed to validate the clinical usefulness of a radiologic decision flow chart based on previously published neuroradiologic knowledge for the diagnosis of posterior fossa tumors in ch...

Considerable progress has been made in the understanding and treatment of paediatric-onset multiple sclerosis (POMS); how this has translated into more effective care is less well understood. Here, we evaluate how recent advances have affected patient management and outcomes with a retrospective review of POMS patients managed at two paediatric neu...

Background The subventricular zone of the third ventricle (TVZ) is a germinal stem cell niche, identified as the possible location of optic pathway glioma (OPG) cell origin. Paediatric OPGs are predominantly diagnosed as low-grade astrocytomas, which are either sporadic or are associated with neurofibromatosis type-1 (NF1). These tumours often caus...

OBJECTIVE. The purpose of this article is to review the characteristic CT and MRI findings associated with monogenetic causes of ischemic and hemorrhagic stroke in children and young adults. CONCLUSION. Ischemic and hemorrhagic stroke in children and young adults remains a common cause of acquired disability but is underrecognized. Brain parenchyma...

Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, with de novo heterozygous and bi...

Background and purpose: Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi-allelic mutations in NKX6-2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. Methods: Using a combination of homozygosity mapping, e...

Background and aims: KIF1A-related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. Here we present a case series demonstrating the range of clinical, neurophysiological and radiological features which may occur in childhood...

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane...

Background: Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi-allelic mutations in NKX6-2 were recently linked to spastic-ataxia 8 with hypomyelinating leukodystrophy (SPAX8). Methods: Using a combination of homozygosity mapping, exome...

Background: Cerebellar Mutism Syndrome (CMS) is a common complication following resection of posterior fossa tumors, most commonly after surgery for medulloblastoma. Medulloblastoma subgroups have historically been treated as a single entity when assessing CMS risk; however, recent studies highlighting their clinical heterogeneity suggest the need...

Objective To compare the performance of the 2017 McDonald criteria with that of the 2010 criteria for the diagnosis of multiple sclerosis (MS) in children in the clinical setting. Methods In this retrospective, multi-centre study, we identified children who presented with symptoms suggestive of a clinically isolated syndrome (CIS) and were followe...

Objective: The aim of this study was to: (a) screen a large group of unselected patients with juvenile systemic lupus erythematosus for anti-aquaporin 4 antibodies (AQP4-Ab); (b) identify clinical and laboratory predictors of the presence of AQP4-Ab positivity in juvenile systemic lupus erythematosus. Methods: Sera from 90 patients with juvenile...

Neuronal migration disorders (NMDs) are a heterogeneous group of conditions caused by the abnormal migration of neuroblasts in the developing brain and nervous system, resulting in severe developmental impairment, intractable epilepsy and intellectual disability (Spalice et al. 2009). To date, many genes have been identified as the leading cause of...

Mutations in the PARK2 gene have been implicated in the pathogenesis of early-onset Parkinson's disease. We present a case of movement disorder in a 4-year-old child from consanguineous parents and with a family history of Dopamine responsive dystonia, who was diagnosed with early-onset Parkinson's disease based on initial identification of a patho...

Background Diffusion- and perfusion-weighted MRI are valuable tools for measuring the cellular and vascular properties of brain tumours. This has been well studied in adult patients, however, the biological features of childhood brain tumours are unique, and paediatric-focused studies are less common. We aimed to assess the diagnostic utility of ap...

The key role of neuroimaging in brain disorders is to assist clinical management by either making a precise diagnosis or providing clinically relevant differential diagnoses. There is a marked diversity of neuropathologies spanning a constellation of conditions including vascular, infectious-inflammatory, degenerative and neoplastic entities, and t...

Response assessment in pediatric neuro-oncology presents unique challenges compared to adult practice. In fact the majority of pediatric tumors are of low grade and can have rather indolent courses with both contrast enhancing and nonenhancing components, often not easily measurable, compared to the adult population where most of the tumors are hig...

Pediatric brain tumors differ from those in adults by location, phenotype and genotype. In addition, they show dissimilar imaging characteristics before and after treatment. While adult brain tumor treatment effects are primarily assessed on MRI by measuring the contrast-enhancing components in addition to abnormalities on T2-weighted and fluid-att...

Introduction: Cerebral hemiatrophy is an uncommon neuroimaging finding of diverse etiologies, conventionally classified into two broad categories: congenital and acquired. The authors propose an alternative pragmatic clinical approach to cerebral hemiatrophy, classifying its diverse etiologies into a single event insult such as an in utero stroke,...

Central nervous system neoplasms are the most common solid tumours that develop in children, with the greatest proportion located in the infratentorium. The 2016 World Health Organization Central Nervous System tumour classification evolved from the 2007 edition with the integration of molecular and genetic profiling into the diagnosis, the additio...

Assessing tumor response is a large part of everyday clinical work in neuroradiology. However in the setting of tumor treatment, distinguishing tumor progression from treatment-related changes is difficult on conventional MRI sequences. This is made even more challenging in children where mainstay advanced imaging techniques that are often used to...

Abusive head trauma (AHT) is a form of inflicted head injury. AHT is more frequent in 2-year-old or younger children. It is an important cause of neurological impairment and the major cause of death from head trauma in this age group. Brain magnetic resonance imaging allows the depiction of retinal hemorrhages, injured bridging veins, and identifyi...

Mutations causing dysfunction of the tubulins and microtubule-associated proteins, otherwise known as tubulinopathies, are a group of recently described entities, that lead to complex brain malformations. An understanding of the fundamental principles of operation of the cytoskeleton and compounds in particular microtubules, actin, and microtubule-...

Purpose: To determine the value of structural magnetic resonance imaging (MRI) in predicting post-operative paediatric cerebellar mutism syndrome (pCMS) in children undergoing surgical treatment for medulloblastoma. Methods: Retrospective cohort study design. Electronic/paper case note review of all children with medulloblastoma presenting to Gr...

Abusive head trauma (AHT) is a significant cause of morbidity and mortality in the paediatric population, typically in children under the age of two years. Neuroimaging plays a key role in the diagnostic work up of these patients as information regarding the mechanism of injury is often lacking and the findings on examination can be nonspecific. A...

There is an extensive and diverse set of medical conditions affecting the neonatal brain within the spectrum of neurometabolic disorders. As such, their clinical presentations can be rather nonspecific, and can often mimic acquired entities such as hypoxic-ischemic encephalopathy and sepsis. Similarly, the radiological findings in these entities ca...

Macrocephaly is a relatively common clinical condition affecting up to 5% of the pediatric population. It is defined as an abnormally large head with an occipitofrontal circumference greater than 2 standard deviations above the mean for a given age and sex. Megalencephaly refers exclusively to brain overgrowth exceeding twice the standard deviation...

Malformations of cortical development (MCD) are a heterogenous group of disorders with diverse genotypic and phenotypic variations. Lissencephaly is a subtype of MCD caused by defect in neuronal migration, which occurs between 12 and 24 weeks of gestation. The continuous advancement in the field of molecular genetics in the last decade has led to i...

Background and purpose: It has been hypothesized that skull marrow signal alteration may represent an early disease manifestation of Sturge-Weber syndrome before development of its intracranial manifestations. We alternatively hypothesized that intraosseous changes are associated with the overlying port-wine stain rather than the intracranial stig...

We assessed DOPA PET for staging (5) or progression (10) in adolescent patients (age 17 ± 4) with brain tumour in comparison with contrast MRI. 15 patients underwent 18 DOPA PET/MRI (2 had repeated follow up) (2 germinoma and 13 gliomas, 7 high grade [HGG] and 6 low grade glioma[LGG]). Two NM physicians recorded quantitative PET parameters. Two neu...

AIM: Stone et al. recently published the molecular characterisation of glioneuronal tumours, classifying them into 2 groups based upon methylation and expression profiles: Group 1 predominantly with BRAF and Group 2 predominantly with FGFR1 mutations. Our aim was to study differentiating neuroimaging features between these two groups on the same pa...

Proton Beam Therapy (PBT) is now well accepted for the treatment of certain pediatric brain tumours. The intrinsic properties of proton radiation are said to theoretically reduce long term negative effects of photon radiation such as cognitive deficits, endocrine and vascular abnormalities, among others. We designed a study to retrospectively descr...

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable chronic disorder of the peripheral nervous system. We retrospectively studied 30 children with a suspected diagnosis of CIDP. The diagnosis of CIDP was compared against the childhood CIDP revised diagnostic criteria 2000. Of the 30 children, five did not meet the criter...

The craniovertebral junction (CVJ) is the bony transition between the cranium and cervical spine. It is a biomechanically complex articulation comprising the occipital condyles (Oc) the atlas (C1) and axis (C2). Pathologies affecting the CVJ in children are myriad with clinical features resulting from biomechanical instability, deformity, or neurax...

Intracranial hemorrhage (ICH) in neonates often results in devastating neurodevelopmental outcomes as the neonatal period is a critical window for brain development. The neurodevelopmental outcomes in neonates with ICH are determined by the maturity of the brain, the location and extent of the hemorrhage, the specific underlying etiology and the pr...

Very often the clinical course of neonatal meningitis (NM) is characterized by sudden worsening, at times associated with cerebrovascular complications and strokes or the formation of cerebral abscesses. The immediate recognition of these pathological patterns is pivotal in providing clinicians with useful information to differentiate between those...

Spastic diplegic cerebral palsy (CP) is the most common form of CP. A specific goal-oriented approach, tailored to the child, is essential to management in all forms of CP. Selective dorsal rhizotomy (SDR) is a neurosurgical procedure that permanently reduces lower limb spasticity in children with spastic diplegic CP. The current technique is perfo...

Introduction: Apert syndrome is one of the most common craniosynostosis syndrome caused by mutations in genes encoding fibroblast growth factor receptor 2 (FGFR2). It is characterized by multisuture craniosynostosis, midfacial hypoplasia, abnormal skull base development and syndactyly of all extremities. Apert syndrome is associated with a wide ar...

Aim: To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated relapsing disease. Method: In this UK-based, multicentre study, 31 children with MOG antibody-associated relapsing disease were studied retrospectively. Results: Of the 31 children studied, 14...

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with oro-facio-digital syndrome phenotype associated to a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and sub-cortical ischemic eve...

Melanotic neuroectodermal tumour of infancy is an uncommon pigmented neoplasm of neural crest origin. It was first described in 1918 by Krompecher, known as congenital melanocarcinoma at that time. Although it is generally agreed upon that it is a benign entity, it is locally aggressive and has a significant recurrent risk, reported to be between 1...

L2-hydroxyglutaric aciduria (L2-HGA) is a rare neurometabolic disease characterised by accumulation of L2-hydroxyglutarate (L2-HG), a potential oncometabolite resulting in significant lifetime risk for cerebral tumors. Here in, we present a case of intraventricular glioblastoma multiforme (GBM) in a 16-year-old child with L2-HGA who presented with...