Veronica Donoghue

Neuroimaging findings in glutaric aciduria type 1

ObjectiveTo review the imaging features of glutaric aciduria type 1 (GA-1) in a group of 20 patients, the largest published series to date. To document the findings not previously reported and compare our findings with the imaging characteristics of GA-1 previously reported in the literature.Materials and methodsFor 14 patients the original scans were examined and in the remaining 6, where the imaging was unavailable, the radiology reports were consulted. Nine patients had serial cranial US examinations, 13 had 18 CT scans performed and 14 patients had 39 MRI scans.ResultsWidening of the sylvian fissures and of the fluid spaces anterior to the temporal lobes was seen in 93% of cases. The mesencephalic cistern was also widened in 86%. Abnormal high-signal intensity on T2-weighted (T2-W) images was seen in the basal ganglia and periventricular white matter in 64% of children. Subdural collections were found in 3 patients, all of which resolved spontaneously. Four neonates followed with serial cranial US showed bilateral multiple caudothalamic cysts. Abnormal high signal on T2-W images was seen in the dentate nucleus, substantia nigra and the pontine medial lemniscus in 79, 43 and 64%, respectively.ConclusionsWidening of the sylvian fissure, mesencephalic cistern and expansion of CSF spaces anterior to the temporal lobes are cardinal signs of GA-1. If combined with abnormalities of the basal ganglia and white matter, GA-1 should be strongly suspected.

Bevacizumab versus diode laser in stage 3 posterior retinopathy of prematurity

Editor, A nti-VEGF agents, primarily bevacizumab, are emerging as a successful therapy for retinopathy of prematurity (ROP), particularly in aggressive posterior disease (Spandau et al. 2013). Concerns exist however regarding dosage, timing, duration of follow-up and long-term visual function. We conducted a prospective case– control study in 14 infants with symmetrical zone 1 or posterior zone 2 Stage 3 + ROP; comparing intravitreal bevacizumab in one eye to laser therapy in the fellow eye. The purpose was to evaluate anatomic outcomes (regression or recurrence of ROP), and functional visual outcomes in the bevacizumab-treated eyes compared with laser-treated eyes, at oneand 2year follow-up. We also evaluated ocular, systemic and developmental outcomes at oneand 2-year followup. Four infants had symmetrical Zone 1 Stage 3 + disease and 10 infants had Zone 2 Stage 3 + disease (Fig. 1). We randomized the eyes into intravitreal bevacizumab (Avastin; Genentech Inc., South San Francisco, CA, USA) versus conventional laser therapy. All procedures were performed in the special-care baby unit (SCBU) under morphine sedation. Intravitreal injection with bevacizumab was performed under aseptic technique using a dose of 1.25 mg in 0.1 ml. After injection of bevacizumab, conventional 360° laser treatment was applied to the fellow eye. The eyes were monitored weekly for 8 weeks, 3 monthly for a further 12 months, and 3–6 monthly thereafter. At 1and 2-year follow-up, a full ocular examination was performed. Electrophysiology testing, visual evoked potential (VEP) and electroretinography (ERG), was performed on each eye where possible. All of the babies had a paediatric examination and magnetic resonance (MR) brain scan. We observed rapid regression of ROP in all eyes injected with bevacizumab, as well as resolution of plus disease and flattening of the ridge by 48 hr postinjection in all eyes. Further vascularization was noted with complete regression taking up to sixty weeks in some eyes. In our study, four of 14 eyes (28.6%) had recurrence of ROP; three eyes (21.42%) which had bevacizumab treatment and one eye (7.14%) with conventional laser therapy. There was a significant time delay to recurrence in the bevacizumab group compared with laser, with a mean age of 51 weeks PMA at time of recurrence in bevacizumab-treated eyes compared with 37 weeks PMA in the laser-treated eye. This delay in recurrence has also been reported by other studies including the BEAT-ROP trial. (Mintz-Hittner et al. 2011). Of the 3 bevacizumab-treated eyes with recurrence, two eyes received laser treatment where the ROP was peripheral. One eye with more posterior recurrence received a further intravitreal bevacizumab injection. In the eyes that received laser treatment, one eye (7.14%) demonstrated recurrent and progressive ROP 1 week following laser treatment (37 weeks PMA) and

The dentate nucleus in children: normal development and patterns of disease

The dentate nuclei lie deep within the cerebellum and play a vital role in the pathways involved in fine motor control and coordination. They are susceptible to a variety of diseases. Some pathological processes preferentially affect the dentate nuclei, while concomitant basal ganglia or white matter involvement can be a striking finding in others. A familiarity with the normal appearance of the dentate nuclei at different ages in combination with the radiological distribution of pathology in the brain allows the paediatric radiologist to develop a logical approach to the interpretation of MR imaging of these deep cerebellar nuclei. In this article we review the normal appearance and MR features of the dentate nuclei, including changes that are seen with myelination. We describe the specific imaging characteristics of childhood diseases that involve the dentate nuclei, and develop a systematic approach to the differential diagnosis of dentate nucleus abnormalities on MR imaging.

Isolated acute non-cystic white matter injury in term infants presenting with neonatal encephalopathy.

We discuss possible aetiological factors, MRI evolution of injury and neuro-developmental outcomes of neonatal encephalopathy (NE). Thirty-six consecutive infants diagnosed with NE were included. In this cohort, four infants (11%) were identified with injury predominantly in the deep white matter on MRI who were significantly of younger gestation, lower birthweight with higher Apgars at one and five minutes compared to controls. Placental high grade villitis of unknown aetiology (VUA) was identified in all four of these infants. Our hypothesis states VUA may induce white matter injury by causing a local inflammatory response and/or oxidative stress during the perinatal period. We underline the importance of continued close and systematic evaluation of all cases of NE, including examination of the placenta, in order to come to a better understanding of the clinical presentation, the patterns of brain injury and the underlying pathophysiological processes.

Ischio-vertebral dysplasia: a distinct entity

Background. Kyphoscoliosis is a complication of some bone dysplasias, including cleidocranial dysplasia. Objectives. We report a distinct disorder with defective ossification of the ischial rami, severe kyphoscoliosis and normal clavicles. Early recognition of this syndrome allows prevention of complications. Materials and methods. All patient cases (aged 1 day to 33 years) were selected according to the above criteria, with special attention to radiological findings, family history and follow-up (5–30 years). Results. In all eight patients, we observed the following: (a) Severe thoracic scoliosis of early onset and rapid progression, leading to rotatory dislocation. Spinal cord compression occurred in four cases with respiratory problems related to chest deformity. (b) Bilateral and symmetrical incomplete ossification of the ischial rami. (c) Peculiar facies with retrognathia. (d) Normal clavicles. Three patients were from the same family (grandmother, mother and daughter). Conclusion. Ischio-vertebral dysplasia seems to represent a true entity, with radiological and genetic findings that make it distinct from cleidocranial dysostosis. The association of kyphoscoliosis and these pelvic abnormalities is specific for this condition. Neurological and respiratory complications can be avoided if the condition is recognised early and early treatment is instituted.

A case of relapsing flitting bilateral idiopathic orbital inflammation

Idiopathic orbital inflammation (IOI) is defined as a benign non-infective clinical syndrome characterized by features of non-specific inflammation of the orbit without identifiable local or systemic causes. This can be called orbital myositis if the inflammation is predominantly in the orbital muscles. It is a diagnosis of exclusion based on clinical, radiological, and if necessary, histological findings. The most commons symptoms are swelling, ptosis, proptosis and painful eye movements. To our knowledge, this patient is the first with IOI to demonstrate relapsing flitting bilateral involvement of several individual extra-ocular muscles.

Gastrointestinal pathology in neonates: new imaging strategies

The mainstay of imaging of gastrointestinal (GI) pathology in infants has always been and still is the plain radiograph of the abdomen and conventional contrast studies. In this review emphasis is placed on the situations where there are new imaging strategies and alternative modalities of imaging, including US, CT, MRI and radionuclide studies. This review will deal with GI pathology in the newborn and in the older neonate. It will also refer to any new approaches to imaging GI pathology in the premature infant. Finally the review will address how antenatal diagnosis of gastrointestinal tract abnormalities has changed the imaging strategy and management of the neonate.

Periorbital ecchymosis ('raccoon eyes') as the presenting feature of neuroblastoma.

A 1-year-old boy presented with an 8-week history of bilateral periorbital ecchymosis (‘raccoon eyes’). Physical examination of the orbits, including neurological examination, was normal. A mass was palpated in the right upper quadrant. US and MRI of the abdomen demonstrated a large right adrenal mass with hepatic metastases. Orbital MRI showed bilateral periorbital metastatic infiltration with involvement of the meninges (Fig. 1). Neuroblastoma is the most common extracranial solid tumour of childhood and accounts for 8–10% of all childhood cancers. Periorbital ecchymosis due to periorbital metastasis complicates approximately 5.4% of cases [1]. It is probably related to obstruction of the palpebral vessels by tumour infiltration around the orbits. Periorbital ecchymosis is also a feature of skull trauma. Hence, diagnosis in these children can be delayed as this can arouse the suspicion of non-accidental injury [2].

Classic metaphyseal lesions follow uncomplicated caesarean section NOT brittle bone disease

Sir, We appreciate the interest shown in our article by Dr. Miller. We do not, however, agree with his suggestion that the metaphyseal fractures identified in the three infants born at our institution over a 22-year period may have been due to a lower newborn bone strength caused by fetal immobilization as a result of their breech presentation or maternal diabetes. Although none of these infants had bone densitometry performed, the plain radiographs obtained showed no evidence of osteopenia. A workload audit is performed annually in our hospital. A review of the past 22 years has revealed a total of 2,313 multiple pregnancies, 2,622 infants who had a breech presentation, 1,814 of whom were delivered by caesarean section and 664 infants born to mothers who had insulindependant diabetes mellitus. Over the past 15 years there have been a further 1,199 infants born to mothers with gestational diabetes. If this large group of infants, as Dr. Miller proposes, were likely to have decreased bone strength and increased susceptibility to fractures, we would expect to have identified many more such metaphyseal injuries. In addition, we are not aware of any reports of an increased incidence of metaphyseal fractures in other institutions caring for similar large patient groups. Finally, we would like to draw Dr. Miller’s attention to the article “Critical review of ‘temporary brittle bone disease’” by Kenneth Mendelson in this journal in 2005, which, following detailed literature analysis, concludes that Miller and Hangartner [1] failed to demonstrate a relationship between fracture patterns and intrauterine confinement or decreased bone density [2].

Persistent systemic monocyte and neutrophil activation in neonatal encephalopathy

Abstract Aim: Circulating immune cell activation is associated with worse outcome in adult and animal models of brain injury. Our aim was to profile the systemic inflammatory response over the first week of life in infants at risk of neonatal encephalopathy (NE) and correlate early neutrophil and monocyte endotoxin and activation responses with outcome. Methods: Prospective observational study in a tertiary referral university hospital including 22 infants requiring resuscitation at birth who had serial (five time points) neutrophil and monocyte CD11b (marker of cell adhesion), intracellular reactive oxygen intermediates (ROI; cell activation) and Toll-like receptor (TLR; endotoxin recognition) before and after endotoxin stimulation ex vivo compared to neonatal controls. Results: All neonates requiring resuscitation at delivery (n = 122 samples) had higher neutrophil and monocyte CD11b and TLR-4 expression compared with adults and neonatal controls. Neonates with abnormal neuroimaging and/or severe NE had increased CD11b, ROI and TLR-4. Increased polymorphonuclear leukocytes TLR-4 expression was associated with increased mortality in infants with NE. Conclusion: Innate immune dysregulation in the first week of life is associated with severity of outcome in neonatal brain injury in this cohort and may be amenable to immunomodulation.