An approach to reporting paediatric leukoencephalopathy and leukodystrophies.

The leukodystrophies (LD) and leukoencephalopathies (LE) are a diverse group of conditions involving the cerebral white and grey matter. There is heterogeneity in the clinical presentations, imaging features, and biochemical dysfunction. Given the number of conditions and varied imaging appearances, this topic can be difficult for non-specialist radiologists who do not routinely work in dedicated paediatric neuroradiology centres. This article will aim to provide a simplified and step-wise approach to assessing suspected LD/LE, focussing on the more common diagnoses you may encounter in the UK. Additionally, it will highlight important non-LD/LE differentials, which if considered early, may significantly alter treatment and prognosis. By the end of this review, we hope the reader will begin to develop an awareness of physiological paediatric brain development in terms of normal myelination; the ability to recognise and categorise the distribution of abnormal signal based on the established diagnostic framework outlined by Schiffmann & Van der Knapp; and be aware of potential non-LD/LE radiological mimics.

Review of the MRI brain findings of septo-optic dysplasia.

AIM: To report the magnetic resonance imaging (MRI) findings from a retrospective case analysis of children with septo-optic dysplasia (SOD), a rare congenital disorder characterised by any combination of midline brain defects, optic nerve hypoplasia (ONH), and hypothalamic-pituitary dysfunction. MATERIALS AND METHODS: SOD was defined radiologically as complete or partial septum pellucidum (SP) absence with hypoplasia of at least one of the optic nerves and/or chiasm. Local MRI databases were searched for SOD cases in children over an 18-year period, and studies reviewed by two consultant paediatric neuroradiologists. The extent of structural SP, optic nerve, chiasm, and hypothalamic-pituitary involvement was recorded, along with coexisting brain abnormalities. RESULTS: Forty-eight cases of SOD were found; 44/48 (92%) demonstrated complete SP absence whereas 4/48 (8%) had partial absence. Eight of 48 cases (17%) exhibited unilateral ONH. Fifty-one percent of cases, where the pituitary was identified on MRI, demonstrated a structural pituitary abnormality, which included an ectopic posterior bright spot in 6%. The olfactory nerves were hypoplastic in 5/48 cases (10%). Twenty-seven of the 48 cases (56%) had another brain abnormality, resulting from some form of cortical formation abnormality/schizencephaly in 21/48 (44%). CONCLUSION: A high rate of associated brain abnormalities was found in the present cohort, including structural pituitary abnormalities in 51% and cortical formation abnormalities/schizencephaly in 44%. This suggests there is not a single cause for SOD, rather SOD is the phenotypic end point from multiple aetiological events. Individual children with SOD may have coexisting intracranial abnormalities, and, hence, high-quality MRI is required in all.

Anatomical subgroup analysis of the MERIDIAN cohort: failed commissuration.

OBJECTIVE: To assess the contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with either agenesis or hypogenesis of the corpus callosum (referred to collectively as failed commissuration) on antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study of fetuses with failed commissuration (with or without ventriculomegaly) diagnosed on ultrasound in women who had MRI assessment within 2 weeks of ultrasound and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI was studied, as well as indicators of diagnostic confidence and effects on prognosis/clinical management. Appropriate diagnostic confidence was assessed by the score-based weighted average method, which combines diagnostic accuracy with diagnostic confidence data. RESULTS: In the MERIDIAN cohort, 79 fetuses were diagnosed with failed commissuration on ultrasound (55 with agenesis and 24 with hypogenesis of the corpus callosum). The diagnostic accuracy for detecting failed commissuration was 34.2% for ultrasound and 94.9% for MRI (difference, 60.7% (95% CI, 47.6-73.9%), P < 0.0001). The diagnostic accuracy for detecting hypogenesis of the corpus callosum as a discrete entity was 8.3% for ultrasound and 87.5% for MRI, and for detecting agenesis of the corpus callosum as a distinct entity was 40.0% for ultrasound and 92.7% for MRI. There was a statistically significant improvement in 'appropriate' diagnostic confidence when using MRI as assessed by the score-based weighted average method (P < 0.0001). Prognostic information given to the women changed in 36/79 (45.6%) cases after MRI and its overall effect on clinical management was 'significant', 'major' or 'decisive' in 35/79 cases (44.3%). CONCLUSIONS: Our data suggest that any woman whose fetus has failed commissuration as the only intracranial finding detected on ultrasound should have MRI examination for further evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Anatomical subgroup analysis of the MERIDIAN cohort: posterior fossa abnormalities.

OBJECTIVE: To assess the diagnostic and clinical contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with abnormalities of the posterior fossa as the only intracranial abnormality recognized on antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study of fetuses with abnormalities of the posterior fossa (with or without ventriculomegaly) diagnosed on antenatal ultrasound in women who had MRI within 2 weeks of ultrasound and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI is reported, as well as indicators of diagnostic confidence and effects on prognosis and clinical management. Appropriate diagnostic confidence was assessed by the score-based weighted average method, which combines diagnostic accuracy with diagnostic confidence data. RESULTS: Abnormalities confined to the posterior fossa according to ultrasound were found in 81 fetuses (67 with parenchymal and 14 with cerebrospinal fluid-containing lesions). The overall diagnostic accuracy for detecting an isolated posterior fossa abnormality was 65.4% for ultrasound and 87.7% for MRI (difference, 22.3% (95% CI, 14.0-30.5%); P < 0.0001). There was an improvement in 'appropriate' diagnostic confidence, as assessed by the score-based weighted average method (P < 0.0001), and a three-fold reduction in 'high confidence but incorrect diagnosis' was achieved using MRI. Prognostic information given to the women changed after MRI in 44% of cases, and the overall effect of MRI on clinical management was considered to be 'significant', 'major' or 'decisive' in 35% of cases. CONCLUSIONS: Our data suggest that any woman whose fetus has a posterior fossa abnormality as the only intracranial finding on ultrasound should have MRI for further evaluation. This is on the basis of improved diagnostic accuracy and confidence, which impacts substantially on the prognostic information given to women as well as their clinical management. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Anatomical subgroup analysis of the MERIDIAN cohort: ventriculomegaly.

OBJECTIVE: To assess the contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with ventriculomegaly (VM) as the only abnormal intracranial finding on antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study of fetuses with only VM diagnosed on ultrasound in women who had a subsequent MRI examination within 2 weeks and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI was reported in relation to the severity of VM. The difference in measurements of trigone size on the two imaging methods and the clinical impact of adding MRI to the diagnostic pathway were also studied. RESULTS: In 306 fetuses with VM, ultrasound failed to detect 31 additional brain abnormalities, having an overall diagnostic accuracy of 89.9% for ultrasound, whilst MRI correctly detected 27 of the additional brain abnormalities, having a diagnostic accuracy of 98.7% (P < 0.0001). There were other brain abnormalities in 14/244 fetuses with mild VM on ultrasound (diagnostic accuracy, 94.3%) and MRI correctly diagnosed 12 of these (diagnostic accuracy, 99.2%; P = 0.0005). There was a close agreement between the size of trigones measured on ultrasound and on MRI, with categorical differences in only 16% of cases, showing that MRI did not systematically overestimate or underestimate trigone size. Complete prognostic data were available in 295/306 fetuses and the prognosis category changed after MRI in 69/295 (23.4%) cases. The overall effect of MRI on clinical management was considered to be 'significant', 'major' or 'decisive' in 76/295 (25.8%) cases. CONCLUSION: Our data suggest that a woman carrying a fetus with VM as the only intracranial finding on ultrasound should be offered an adjuvant investigation by MRI for further evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Change in diagnostic confidence brought about by using in utero MRI for fetal structural brain pathology: analysis of the MERIDIAN cohort.

AIM: To measure possible change in diagnostic confidence by performing in utero magnetic resonance imaging (iuMRI) studies on fetuses with brain abnormalities recognised on ultrasonography (US). MATERIALS AND METHODS: The analyses are based on the primary cohort from the prospective MERIDIAN study, which consisted of 570 fetuses with brain abnormalities detected on US, with iuMRI performed within 2 weeks of US and complete outcome reference data. The cohort was recruited between July 2011 and August 2014, and written informed consent was obtained for all participants. They all had indicators of diagnostic confidence measured on US by fetal medicine experts and iuMRI by the reporting radiologists. Three assessments were carried out using the conventional uncorrected (C2-C1%) method, the conventional (C2-C1%) with the Omary correction, and the score-based weighted average method. RESULTS: All three assessments showed statistically significant (p<0·0001) positive effects indicating that iuMRI was potentially beneficial when included in the diagnostic pathway for prenatal structural brain anomalies (in terms of diagnostic confidence). CONCLUSION: These results strongly support the routine clinical use of iuMRI as an adjunct to US when assessing fetuses with structural brain abnormalities.

A pictorial review of imaging in paediatric stroke.

Stroke is recognised as an important disease in adults. Paediatric stroke is less understood, yet still an important cause of morbidity and mortality, with an incidence of 5 per 100 000 children and is one of the top 10 leading causes of death in children. In adults the vast majority of strokes are ischaemic, whereas in children haemorrhage makes up half the cases. The incidence of neonatal stroke is much higher, at up to 45 per 100 000 population; however, the underlying causes are less understood. This paper acts as a guide to the different causes of stroke with the key differences on imaging discussed.

Paediatric post-septal and pre-septal cellulitis: 10 years' experience at a tertiary-level children's hospital.

OBJECTIVE: To assess the incidence and complications of pre-septal (pre-SC) and post-septal (post-SC) cellulitis over 10 years. Pre-SC and post-SC are also known as periorbital and orbital cellulitis, respectively. METHODS: Retrospective analysis of CT scans. Data included the presence of pre-SC and post-SC, paranasal sinus disease (PNS) and complications. RESULTS: Among 125 patients scanned for these suspected diagnoses, 67 had both pre-SC and post-SC, 37 had pre-SC and 4 had post-SC; there were 17 normal scans. 110 patients had PNS. 68/71 (96%) patients with post-SC had PNS. Post-SC complications included orbital and/or subperiosteal abscess (50/71: 30 medial orbital, 10 superomedial, 3 lateral, 2 anteromedial, 2 inferomedial, 1 superior, 1 anterosuperior and 1 not specified), cavernous sinus thrombosis (CST) (1), superior ophthalmic vein (SOV) thrombosis (4) and subdural frontal empyema (2); 1 patient had SOV and CST and subdural empyema. CONCLUSION: 71/125 (57%) patients had post-SC. 50/125 (40%) patients imaged for pre-SC/post-SC had orbital abscess; 44/50 (88%) of these involved the medial orbit. Patients can develop solely superior or inferior abscesses that are difficult to identify by axial imaging alone, hence coronal reformatted imaging is essential. 5/125 (4%) patients developed major complications (SOV/CST/empyema), hence imaging review of the head and cavernous sinus region is essential. A diagnosis of post-SC on CT should alert the radiologist because this diagnosis can be associated with an increased incidence (5/71, 7%) of complications. ADVANCES IN KNOWLEDGE: We recommend that all patients with a suspected diagnosis of post-SC should undergo CT scan (post-contrast orbits and post-contrast head, with multiplanar reformats and a careful review of the SOV and the cavernous sinus). Particular attention should be paid to exclude intracranial complications including subdural empyema and cerebral abscess. As soon as a diagnosis of post-SC is made, in addition to informing the referring clinical team, urgent opinion should be sought from ear, nose and throat (ENT), neurology and ophthalmology with a view to urgently drain of the paranasal sinuses`.

Diffuse intrinsic pontine glioma treated with prolonged temozolomide and radiotherapy--results of a United Kingdom phase II trial (CNS 2007 04).

Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis with no chemotherapy regimen so far resulting in any significant improvement over standard radiotherapy. In this trial, a prolonged regimen (21/28d) of temozolomide was studied with the aim of overcoming O(6)-methylguanine methyltransferase (MGMT) mediated resistance. Forty-three patients with a defined clinico-radiological diagnosis of DIPG received radiotherapy and concomitant temozolomide (75 mg/m(2)) after which up to 12 courses of 21d of adjuvant temozolomide (75-100mg/m(2)) were given 4 weekly. The trial used a 2-stage design and passed interim analysis. At diagnosis median age was 8 years (2-20 years), 81% had cranial nerve abnormalities, 76% ataxia and 57% long tract signs. Median Karnofsky/Lansky score was 80 (10-100). Patients received a median of three courses of adjuvant temozolomide, five received all 12 courses and seven did not start adjuvant treatment. Three patients were withdrawn from study treatment due to haematological toxicity and 10 had a dose reduction. No other significant toxicity related to temozolomide was noted. Overall survival (OS) (95% confidence interval (CI)) was 56% (40%, 69%) at 9 months, 35% (21%, 49%) at 1 year and 17% (7%, 30%) at 2 years. Median survival was 9.5 months (range 7.5-11.4 months). There were five 2-year survivors with a median age of 13.6 years at diagnosis. This trial demonstrated no survival benefit of the addition of dose dense temozolomide, to standard radiotherapy in children with classical DIPG. However, a subgroup of adolescent DIPG patients did have a prolonged survival, which needs further exploration.

CT of the neonatal head.

Computed tomography (CT) is used less often than other techniques on neonatal units. However, in the acute setting, CT can be invaluable in diagnosing or excluding potentially life-threatening conditions and guiding initial management in neonates. Common indications for scanning include trauma, suspected non-accidental injury, infection, or an acute hypoxic or metabolic event. The aim of this review is to provide an overview of the normal neonatal head at CT and compare this to the common pathological abnormalities. Several key features of each condition will be highlighted. It is important to note that some pathological conditions can have overlapping features at CT and, therefore, the clinical history and additional investigations are also of key importance in determining the diagnosis.

Management of isolated syringomyelia in the paediatric population--a review of imaging and follow-up in a single centre.

OBJECTIVE: To assess the natural history of isolated syringomyelia in children. METHODS: MRI reports from February 2007 to August 2011 mentioning syrinx were identified on Sheffield Children's PACS database. Scans with syringes having an AP diameter of > 1 mm and extending over at least two vertebral bodies were reviewed. Patients with an identifiable cause such as a Chiari malformation were then excluded. RESULTS: Thirty-nine patients were included with a mean age at diagnosis of 10.6 years. The average syrinx AP diameter was 3.30 mm. The rostrocaudal length of the syringes varied between 2 and 19 vertebral bodies. Twenty-seven out of 39 syringes were thoracic in origin. There were 3 and 6 syringes involving the cervicothoracic and thoracolumbar regions, respectively, with 3 involving the cervical area only. Eleven out of 39 (Group I) patients were found "incidentally" during work-up for adolescent idiopathic scoliosis and these were considered as a separate group. These patients did not have any significant symptoms and were discharged following their scoliosis correction surgery. Syrinx was incidental in 14 further patients (Group II). Of the 14 patients, 11 remained asymptomatic with no change in syrinx morphology throughout follow up. Of the 14 patients, 3 were lost to follow-up. Of the 39 patients, 14 (Group III) presented with progressive back pain without any obvious clinical cause. Of the 14, 10 either improved or remained the same. Of the 14 patients, 3 underwent lumbar puncture, 1/14 having myelography. All 4/14 patients reported significant pain reduction on follow up following intervention. CONCLUSION: Idiopathic syrinx is a benign pathology, which can be managed expectantly. Most cases remain stable or improve over time. In a small minority who have progressive back pain, we have found that lumbar puncture may be helpful in reducing symptoms.

The role of MRI and CT of the brain in first episodes of psychosis.

AIM: To investigate whether imaging is associated with early detection of the organic causes of the first episode of psychosis (FEP). MATERIALS AND METHODS: Individuals with FEP but no neurological signs referred to a tertiary centre for cerebral magnetic resonance imaging (MRI) or computed tomography (CT) were reviewed retrospectively. Two groups were evaluated with either CT or MRI; the two groups were independent and no individual underwent both CT and MRI. RESULTS: One hundred and twelve consecutive cerebral MRI and 204 consecutive CT examinations were identified. Three (2.7%) individuals had brain lesions [brain tumour and human immunodeficiency virus (HIV) encephalopathy] potentially accountable for the psychosis at MRI. Seventy patients (62.5%) had incidental brain lesions, such as cerebral atrophy, small vessel ischaemic changes, unruptured Circle of Willis aneurysm, cavernoma, and arachnoid cysts at MRI. Three patients (1.5%) had focal brain lesions (primary or secondary tumours) potentially accountable for the psychosis at CT. One hundred and thirty-three patients (65.2%) had incidental brain lesions unrelated to the psychosis on CT scan. There was no significant difference between MRI and CT imaging in detecting organic disease potentially responsible for FEP (p < 0.001). CONCLUSION: Routine MRI or CT imaging of the brain is unlikely to reveal disease leading to a significant change in management. MRI was comparable with CT in terms of diagnosis of both pathological and incidental cerebral lesions. Therefore, routine brain structural imaging of FEP in patients without focal neurology may not be routinely required and if imaging is requested then CT may function equally as well as MRI as the first-line investigation.

MRI protocols for imaging paediatric brain tumours.

AIMS: To establish whether paediatric centres within the Children's Cancer and Leukaemia Group (CCLG) network employ magnetic resonance imaging (MRI) protocols for brain tumours according to the revised guidance. MATERIALS AND METHODS: Questionnaires were sent to both consultants and superintendent radiographers in the 21 centres within the CCLG network that perform MRI on paediatric brain tumour patients. Information was requested as to whether the centre had a protocol for imaging paediatric brain tumours, which sequences were performed, and whether these were used by all consultants. RESULTS: Twenty-seven completed questionnaires out of the 42 sent were returned, which included responses from 17 of the 21 UK centres. The majority of centres had a protocol for MRI of paediatric brain tumours at all stages of treatment. The standardized CCLG MRI sequences were incorporated in full at only five of the 17 centres. CONCLUSION: The standard sequences of the CCLG brain imaging protocol are poorly adhered to nationally. Further awareness of the revised protocol is needed, with improved access to the guidelines for non-CCLG members on the CCLG and Royal college of Radiologists website.

3.0 T MRI of 2000 consecutive patients with localisation-related epilepsy.

OBJECTIVES: Clinical guidelines suggest that all patients diagnosed with localised seizures should be investigated with MRI to identify any epileptogenic structural lesions, as these patients may benefit from surgical resection. There is growing impetus to use higher field strength scanners to image such patients, as some evidence suggests that they improve detection rates. We set out to review the detection rate of radiological abnormalities found by imaging patients with localised seizures using a high-resolution 3.0 T epilepsy protocol. METHODS: Data were reviewed from 2000 consecutive adult patients with localisation-related epilepsy referred between January 2005 and February 2011, and imaged at 3.0 T using a standard epilepsy protocol. RESULTS: An abnormality likely to be related to seizure activity was identified in 403/2000 (20.2%) patients, with mesial temporal sclerosis diagnosed in 211 patients. 313/2000 (15.6%) had lesions potentially amenable to surgery. Abnormalities thought unrelated to seizure activity were found in 324/2000 (16.1%), with 8.9% having evidence of ischaemic disease. CONCLUSIONS: Since the introduction of the then National Institute for Clinical Excellence guidelines in 2004, the detection rate of significant pathology using a dedicated 3.0 T epilepsy protocol has not fallen, despite the increased numbers of patients being imaged. This is the largest study of epilepsy imaging at 3.0 T to date and highlights the detection rates of significant pathology in a clinical setting using a high-strength magnet. The prevalence of ischaemic disease in this population is significantly higher than first thought, and may not be incidental, as is often reported.

Neuroimaging in non-accidental head injury in children: an important element of assessment.

Head injury from physical abuse is unfortunately a common occurrence in our society. It is a major cause of mortality and long-term physical and psychological disability in children. Diagnosis of non-accidental head injury may be difficult, as most infants present with non-specific clinical findings and without external signs of trauma. Neuroimaging plays a fundamental role both for medical management and medicolegal aspects of child abuse. It is therefore imperative for the radiologist to promptly recognise the radiological findings of various forms of non-accidental head injury to render a more accurate opinion. A standardised imaging protocol and good communication between professionals are essential for optimum management.

The encephalopathic child.

Encephalopathy is a common paediatric emergency associated with a high risk of morbidity, mortality and long term neurodevelopmental delay in survivors. Prompt diagnosis of the cause of encephalopathy enables the paediatrician to deliver specific medical or surgical treatment that will facilitate a better short and long term outcome. Diagnostic imaging plays a pivotal role in diagnosis. Encephalopathy has many causes. The differential diagnosis includes non accidental injury, trauma, metabolic syndromes, meningo-encephalitis, toxins, hypoxia, demyelination, stroke, haemorrhage and tumours. We describe an approach that helps us formulate an imaging strategy using US, CT and MRI that facilitates patient care.

Role of imaging in the diagnosis of acute bacterial meningitis and its complications.

Acute bacterial meningitis is a common neurological emergency and a leading cause of death and neurological disability worldwide. Diagnosis is based on clinical and microbiological findings with neuroimaging in the form of CT reserved for those with specific adverse clinical features or when an underlying cause such as mastoiditis is suspected. MRI is extremely useful for detecting and monitoring the complications of meningitis. These can be remembered by the mnemonic HACTIVE (hydrocephalus, abscess, cerebritis/cranial nerve lesion, thrombosis, infarct, ventriculitis/vasculopathy and extra-axial collection). Diffusion weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) are useful to distinguish abscess from other ring enhancing lesions.

Dimensions and ossification of the normal anterior cranial fossa in children.

BACKGROUND AND PURPOSE: Interpretation of CT of the anterior skull base in children depends on knowledge of the pattern and chronology of ossification. The purpose of this study was to ascertain the age at which the anterior cranial fossa is fully ossified as assessed on CT examinations. MATERIALS AND METHODS: This was a retrospective review of 127 CT examinations of children ranging from 1 day to 16 years 7 months of age without known or suspected anterior cranial fossa abnormality. Measurements of the length and width of the anterior skull base and the presence and size of the most anterior unossified portion were determined by 2 investigators. RESULTS: At birth, the anterior skull base consists mainly of cartilage. There is a wide variation in ossification rates between individuals, but the anterior skull base was fully ossified at 3 years 10 months in all of our cases. CONCLUSIONS: In healthy individuals, the anterior skull base is fully ossified by 4 years of age.

Assessment of sulcation of the fetal brain in cases of isolated agenesis of the corpus callosum using in utero MR imaging.

BACKGROUND AND PURPOSE: There is gathering evidence to suggest that agenesis of the corpus callosum is associated with delayed fetal sulcation; it is possible that the corpus callosum facilitates normal gyral development. In this paper we sought to confirm whether delayed sulcation is found in fetuses with isolated agenesis of the corpus callosum as judged by in utero MR imaging. MATERIALS AND METHODS: Retrospective analysis of 20 fetuses with isolated corpus callosum agenesis investigated by in utero MR imaging and 20 aged-matched normal fetuses was performed in the second or third trimester. All fetuses were singleton pregnancies with known gestational age, imaged on a 1.5T superconducting MR system. Estimation of sulcation maturity was made with reference to a standard atlas and subgroup analysis of earlier gestation (group 1, 21-26 weeks) and later gestation (group 2, 30-34 weeks) fetuses was performed. RESULTS: Group 1 (n = 12) did not show a statistically significant difference between the 2 subgroups (P = .44) in terms of sulcation. A significant difference was demonstrated in the later gestation, group 2 (n = 8) fetal analyses; mean difference between consensus and actual gestation for normal fetuses was 0.9 weeks (SD of 1.5 weeks) versus -0.5 weeks (SD of 1.1 weeks) for the agenesis of corpus callosum cases (P = .046), suggestive of delayed sulcation in callosal agenesis. CONCLUSIONS: Delayed sulcation encountered in third trimester fetuses with agenesis of the corpus callosum may be seen and does not in itself imply an additional brain abnormality.