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Purpose To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. Methods We report on six patients with NF‐1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. Results Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4–28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life‐threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1–2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. Conclusion Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF‐1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients., Here, we report on response to Trametinib, a MEK inhibitor in children with NF‐1. Our experience presented in this report demonstrates that Trametinib is an effective therapy for advanced, life‐threatening PNF, and treatment‐refractory PLGG in patients with NF‐1 and is well tolerated in children.

The processing of instant coffee may involve pumping the material in a melt phase through operations at elevated pressures. The shear rheology of this material was investigated using the Cambridge multipass rheometer, which allows for shear rheometric testing under conditions of independently controlled temperature and pressure. In this work the back pressure was set to dissolve any air that was present in the melt, so that the rheology of the single phase material could be tested. Data were collected over the accessible range of conditions; shear rates from 0.01 to 1000 s −1 , temperatures from 80 to 110 °C, and pressures from 0.01 to 300 bar. The melt exhibited thixotropic behaviour at low shear rates, and the data could be fitted to a non-dimensionalised Carreau fluid model with a temperature dependence which followed an Andrade relationship. Sample to sample variation was observed, which is attributed to differing water content. The results demonstrate how the rheology of complex food materials can be accessed under process conditions., This work was supported by Mondelēz International, Jacob Douwe Egberts, and the Engineering and Physical Sciences Research Council.

Alexander Disease (AD) is a rare and ultimately lethal leukodystrophy, typically presenting in infants who exhibit developmental delay, macrocephaly, seizures, spasticity and quadriparesis. Classic infantile forms are generally due to sporadic mutations in GFAP that result in the massive deposition of intra-astrocytic Rosenthal fibres, particularly in the frontal white matter. However, phenotypic manifestations are broad and include both juvenile and adult forms that often display infratentorial pathology and a paucity of leukodystrophic features. We describe the unique case of an 8.5 year old female who presented with an 8 month history of progressively worsening vomiting and cachexia, whose extensive multidisciplinary systemic workup, including GI biopsies, proved negative. Neuroimaging ultimately revealed bilaterally symmetric and anterior predominant supratentorial signal alterations in the white matter plus a 1.7 x 1.2 x 0.7 mm right dorsal medullary mass. Biopsy of this presumed low-grade glioma revealed features in keeping with AD, which was later confirmed on whole exome sequencing. The proband exhibited a pathogenic p.Arg239Cys heterozygous missense mutation in GFAP, which was apparently inherited from her asymptomatic mother (1% mosaicism in the mother’s blood). Germline mosaic inheritance patterns of young-onset AD, particularly those presenting with a tumor-like mass of the brainstem, are scarcely reported in the literature and serve to expand the clinicopathologic spectrum of AD.LEARNING OBJECTIVESThis presentation with enable the learner to: 1.Recognize an uncommon clinical presentation of AD.2.Describe the underlying genetics of AD, including a rare familial juvenile onset form featuring germline mosaicism.

This paper details an investigation into the separation of Hexamethylenediamine (HMD) from dilute aqueous solutions by exploiting phase separation. HMD is a monomer used in the production of Nylon-6,6 and as such this separation is potentially useful in extracting purifying HMD produced from biological sources or reclaimed from waste made by the production of nylon. An investigation was undertaken into the effect of using sodium hydroxide (NaOH) to promote the phase separation, and a model was derived to predict this behaviour. Furthermore, the effect of various salts on this phase separation was investigated, and it was found that sodium sulphate and sodium carbonate promote the phase separation, but are unable to cause phase separation without the presence of sodium hydroxide.

When I arrived in New York thirty years ago, one of the first assignments I gave myself was to make sure to meet Mary Erler, an English professor at Fordham who had published an important article elucidating the care for books at Syon Abbey as it was described in the sacristan's account rolls of the early sixteenth century. Mary and I have stayed in touch ever since, sharing our common interest in Henry V's two great religious houses, that of Brigittine nuns and brothers at Syon, northwest across the Thames from Richmond Palace, and the Carthusian monastery of Jesus of Bethlehem at Sheen, on the southeast bank of the Thames, to the west of the palace grounds. Much of Mary's work has been on women's readership, spirituality, and associational networks (particularly through the medium of book production, ownership, gift, and bequest) in the later medieval and early modern period in England – with Syon Abbey as a constant thread in the web of her interests. A major part of my own interest has been in the production, transmission, and ownership of books among the later medieval English Carthusian monks – the nexus of textual, material, and social connection that the surviving manuscripts and early prints of these works embody – and the critical edition of some of the texts in these books. One of the strongest of these nexus of connection has been Syon Abbey; and the present paper is a study of the nexus of Syon Abbey and The Scale of Perfection , for there is a strong link between the two, a link formed in large part by the affective reading of the Scale by the nuns of Syon. Of the twenty-one surviving manuscripts originally containing the complete English text of the Scale , three have connections to Syon Abbey. These manuscripts are all affiliated with what I have termed the “Carthusian Group” of manuscripts of Scale II, although, to be fair, it could just as well have been given the somewhat more cumbersome title the “Carthusian-Brigittine Group.” This group comprises nine manuscripts and the 1494 Wynkyn de Worde editio princeps of the Scale ( STC 14042: all later printings in fact derive from this one), plus two manuscripts that represent conflation of the Carthusian group with some other. All manuscripts of the Carthusian group contain both books of the Scale .

OBJECTIVE Refractory symptomatic plexiform neurofibromas (PNF) and inoperable refractory low grade gliomas (LGG) pose a clinical challenge that may be life threatening. Phase 1 and 2 clinical trials of MEK inhibition with selumetinib in inoperable PNF and LGG have demonstrated promising results in pediatrics, however access has been limited to enrollment on clinical trial. Phase 1 clinical trial for trametinib a MEK 1 and 2 inhibitor has been completed, publication is pending. Thus we have treated a series of children on a compassionate basis with extensive PN or LGG refractory disease with trametinib, as this is available in Canada. METHODS We have treated children with trametinib on a compassionate basis in our province since 2017. Review of the clinical data regarding this therapy has been IRB approved. RESULTS Two young patients were treated for indication of life threatening extensive PNF and have had tumor shrinkage and improvement of clinical status. Treatment has been complicated by paronychiae, eczema exacerbation, chondrodermatitis nodularis helicis, RSV and influenza B infection and CTCAE grade 2 pneumonia. In spite of the side effects these two patients remain on treatment due to clear benefit from therapy including: improved respiratory compromise, hearing and dysphagia. We will present the data of additional patients treated with trametinib. CONCLUSION Trametinib is an effective therapy for life threatening PNF by changing the natural history of tumor growth in young children. Further data is required in terms of tolerance, efficacy and durability of response in such patients in the setting of clinical trials.

Nicholas Love was the prior of the Carthusian house of the Assumption of the Blessed Virgin Mary at Mount Grace from its incorporation into the Order at the General Chapter of 1410 until shortly before his death, which occurred between 15 March and 28 July, 1423. He is most commonly known to present-day scholarship as the author of The Mirror of the Blessed Life of Jesus Christ and because of the licensing of the Mirror by Archbishop Thomas Arundel in accordance with the stipulations of the Lambeth Constitutions of 1409, as an agent in the archbishop's campaign against the followers of John Wyclif, and against Wycliffite translation of the scriptures into the vernacular. It would be better, however, to see him as an actor in his own right, a promoter, like his continental European Carthusian confrères, of the reform of the western Church in the fifteenth century.

High-dose steroid administration is no longer recommended in the treatment of acute traumatic brain injury (TBI) as it failed to prove beneficial in improving patients’ outcome. However, a masked benefit of steroid administration in TBI management was that it provided corticosteroid replacement therapy in patients with TBI-related central adrenal insufficiency. We report the case of a 12-year-old boy who suffered a severe TBI from a motor vehicle accident that resulted in complete deficiency of anterior pituitary function. Central adrenal insufficiency was not ruled out by a near normal response to a low-dose ACTH test performed on D11. Consideration should be given to the empirical treatment of TBI pediatric patients with stress doses of corticosteroids if injury to the hypothalamus or pituitary gland is possible until a formal assessment of the hypothalamic—pituitary—adrenal axis can be made.

Background: Creatine transporter deficiency (CTD) is an X-linked inborn error of creatine metabolism characterized by reduced intra-cerebral creatine, developmental delay/intellectual disability, (ID), behavioral disturbance, seizures, and hypotonia in individuals harboring mutations in the SLC6A8 gene. Treatment for CTD includes supplementation with creatine, either alone or in combination with creatine precursors (arginine or glycine). Unlike other disorders of creatine metabolism, the efficacy of its treatment remains controversial. Methods: We present our systematic literature review (2001-2013) comprising 7 publications (case series/reports), collectively describing 25 patients who met the inclusion criteria, and 3 additional cases treated at our institution. Definitions were established and extracted data analyzed for cognitive ability, psychiatric and behavioral disturbances, epilepsy, and cerebral proton magnetic resonance spectroscopy measurements at pre- and post-treatment. Results: Treatment regimens varied among the 28 cases: 2 patients received creatine-monohydrate supplementation; 7 patients received L-arginine; 2 patients received creatine-monohydrate and L-arginine; and 17 patients received a combination of creatine-monohydrate, L-arginine and glycine. Median treatment duration was 34.6 months (range 3 months-5 years). Level of evidence was IV. A total of 10 patients (36%) demonstrated response to treatment, manifested by either an increase in cerebral creatine, or improved clinical parameters. Seven of the 28 patients had quantified pre- and post-treatment creatine, and it was significantly increased post-treatment. All of the patients with increased cerebral creatine also experienced clinical improvement In addition, the majority of patients with clinical improvement had detectable cerebral creatine prior to treatment. 90% of the patients who improved were initiated on treatment before nine years of age. Conclusions: Acknowledging the limitations of this systematic review, we conclude that a proportion of CTD patients show amenability to treatment-particularly milder cases with residual brain creatine, and therefore probable residual protein function. We propose systematic screening for CTD in patients with ID, to allow early initiation of treatment, which currently comprises oral creatine, arginine and/or glycine supplementation. Standardized monitoring for safety and evaluation of treatment effects are required in all patients. This study provides effectiveness on currently available treatment, which can be used to discern effectiveness of future interventions (e.g. cyclocreatine). (C) 2014 Elsevier Inc. All rights reserved

The phenotype of recurrent ∼600 kb microdeletion and microduplication on proximal 16p11.2 is characterized by a spectrum of neurodevelopmental impairments including developmental delay and intellectual disability, epilepsy, autism and psychiatric disorders which are all subject to incomplete penetrance and variable expressivity. A variety of brain MRI abnormalities were reported in patients with 16p11.2 rearrangements, but no systematic correlation has been studied among patients with similar brain anomalies, their neurodevelopmental and clinical phenotypes. We present three patients with the proximal 16p11.2 microduplication exhibiting significant developmental delay, anxiety disorder and other variable clinical features. Our patients have abnormal brain MRI findings of cerebral T2 hyperintense foci (3/3) and ventriculomegaly (2/3). The neuroradiological or neurological findings in two cases prompted an extensive diagnostic work-up. One patient has exhibited neurological regression and progressive vision impairment and was diagnosed with juvenile neuronal ceroid-lipofuscinosis. We compare the clinical course and phenotype of these patients in regard to the clinical significance of the cerebral lesions and the need for MRI surveillance. We conclude that in all three patients the lesions were not progressive, did not show any sign of malignant transformation and could not be correlated to specific clinical features. We discuss potential etiologic mechanisms that may include overexpression of genes within the duplicated region involved in control of cell proliferation and complex molecular mechanisms such as the MAPK/ERK pathway. Systematic studies in larger cohorts are needed to confirm our observation and to establish the prevalence and clinical significance of these neuroanatomical abnormalities in patients with 16p11.2 duplications.

BACKGROUND: To evaluate the predominant pattern of brain injury and the anatomic areas of injury in children with infantile spasms following neonatal hypoxic-ischemic encephalopathy. METHODS: A nested case-control study of infantile spasms in children with term neonatal hypoxic-ischemic encephalopathy was performed. All patients had T1/T2-weighted magnetic resonance imaging with diffusion-weighted imaging performed on the third day of life. Using a validated scoring system, the magnetic resonance imaging was classified as: normal, watershed, basal ganglia/thalamus, total, or focal-multifocal. Two study investigators scored additional anatomic areas of injury (cortical extent, levels of the brainstem, hypothalamus) on T1/T2-weighted magnetic resonance imaging and diffusion-weighted imaging blinded to the outcome. The predominant pattern of brain injury and anatomic areas of injury were compared between patients who developed infantile spasms and randomly selected controls. RESULTS: Eight patients who developed infantile spasms were identified among a cohort of 176 term newborns with hypoxic-ischemic encephalopathy (4.5%). There were no significant differences in the perinatal and neonatal course between newborns who developed infantile spasms and controls who did not. The development of infantile spasms after neonatal hypoxic-ischemic encephalopathy was significantly associated with basal ganglia/thalamus and total brain injury (P ¼ 0.001), extent of cortical injury greater than 50% (odds ratio ¼ 11.7, 95% confidence interval ¼ 1.1-158.5, P ¼ 0.01), injury to the midbrain (odds ratio ¼ 13, 95% confidence interval ¼ 1.3-172, P ¼ 0.007) and hypothalamic abnormalities (P ¼ 0.01). CONCLUSIONS: The development of infantile spasms after hypoxic-ischemic encephalopathy is associated with injury to the basal ganglia and thalami on neonatal magnetic resonance imaging, particularly when extensive cortical injury and/or injury to the midbrain is present.

Serial change in ventricular size is recognized as an imperfect indicator of ongoing hydrocephalus in children. Potentially, other radiographic features may be useful in determining the success of hydrocephalus interventions. In this study, optic nerve sheath diameter (ONSD), optic nerve tortuosity, and optic disk bulging were assessed as indicators of hydrocephalus control in children who underwent endoscopic third ventriculostomy (ETV) or posterior fossa tumor resection. Sixteen children underwent ETV or tumor resection for treatment of hydrocephalus. T2-weighted axial magnetic resonance images of the orbit were obtained, and the ONSD was measured posterior to the optic globe, pre- and post-intervention. Evidence of optic disk bulging and optic nerve tortuosity was also assessed. Ventricular size was estimated using the frontal and occipital horn ratio (FOR). There was a significant reduction in the ONSD post-ETV (n = 9) and after tumor resection (n = 7). Average preoperative ONSD was 6.21 versus 5.71 mm postoperatively (p = 0.0017).There was also an 88 % (p = 0.011) and 60 % (p = 0.23) reduction in optic disk bulging and tortuosity, respectively. The FOR normalized in the tumor resection group but not the ETV group. After intervention, all patients showed improvement in signs and symptoms of hydrocephalus. In our study population, ONSD decreased in response to measures to reduce hydrocephalus. Optic disk bulging also appears to resolve. Serial reduction in ONSD, and optic disk bulging may be indicators of improved hydrocephalus following pediatric neurosurgical interventions.

Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

Subcutaneous nodules of the scalp are common and usually benign. We describe a case that presented as a probable inclusion cyst or lipoma of the scalp that was discovered to be a benign osteolytic fibrohistiocytic lesion of the frontoparietal skull. This ultimately was successfully treated by neurosurgery with a craniectomy, tumor excision, and reconstructive cranioplasty.

Modeling and simulation (MS and (2) a human performance model integrated with the system model. These two models gave very different predictions of mission performance. The case is made that human performance modeling is an essential component of M&S when the intent is to understand total system performance.

Purpose To evaluate the outcome of ophthalmic complications in children with otitis media. Methods The records of children with ophthalmic complications arising from otitis media who presented to the British Columbia Children's Hospital between August 2006 and March 2008 were reviewed retrospectively. Results Of 1,400 patients presenting to the emergency department for otitis media during the study period, 7 with ophthalmic complications were identified (age range, 1-11 years). All patients had abducens nerve palsy on presentation. Other notable ophthalmic complications included papilledema, Horner syndrome, and proptosis. Extracranial and intracranial complications included mastoiditis, petrositis, parapharyngeal abscess, hydrocephalus, epidural abscess, and cerebral venous thrombosis, including cavernous sinus thrombosis in 2. Of the 7 patients, 6 were treated with surgery, including myringotomy and tube placement (6 patients) and mastoidectomy (3 patients). All patients were initially anticoagulated and received intravenous antibiotics. Satisfactory final visual outcomes and stereopsis ranging from 40 to 100 seconds were achieved in all patients. Conclusions Ophthalmic complications of otitis media in children are likely to include abducens palsy. All patients in our series required anticoagulation and intravenous antibiotics. Most required otolaryngologic surgery, but none required strabismus surgery, and all patients had satisfactory visual and ocular motility outcomes.

Diagnosis of mitochondrial disease is often a challenge because of the extreme heterogeneity of the clinical phenotype and the variety of underlying gene defects. Insight into the range of clinical phenotypes associated with a particular mitochondrial DNA mutation will facilitate better recognition of patients at risk by focused gene testing. We present a family affected by the mitochondrial m.13513G>A (p.D393N, ND5) mutation, illustrating a previously unreported degree of clinical heterogeneity, varying from mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) in a 10-year-old female, to a fatal neonatal course with metabolic acidosis and hypotonia in a younger sister, to absence of medical problems in the mother. The mutation loads ranging from 66% in the deceased neonate to 30% in the female with MELAS and 7% in the asymptomatic mother, correlated with severity of the clinical phenotype. The importance of proactive collection and storage of appropriate samples during the diagnostic work-up of an acutely ill or deceased neonate, allowing subsequent mitochondrial investigations, is hereby illustrated.

Object The criteria for identifying patients in whom endoscopic third ventriculostomy (ETV) provides control of hydrocephalus remain in evolution. In particular, it is not clear when ETV would be effective if intraventricular obstruction is not found preoperatively. The authors postulated that 1) displacement of the third ventricle floor inferiorly into the interpeduncular cistern and displacement of the lamina terminalis anteriorly into the lamina terminalis cistern could predict clinical success of ETV, and 2) improvement in these displacements would correlate with the success of ETV. Methods Magnetic resonance imaging in 38 consecutive patients treated between 2004 and 2010 was reviewed to assess displacement of the lamina terminalis and third ventricular floor prior to and following ETV. Displacements of the floor and lamina terminalis were judged qualitatively and quantitatively, using a newly created index, the Third Ventricular Morphology Index (TVMI). The association between the aforementioned morphological features and clinical success of ETV was analyzed. Results Ninety-six percent of patients in whom the authors preoperatively observed displacement of the lamina terminalis and the third ventricular floor were successfully treated with ETV. Displacements of the third ventricular floor and lamina terminalis, as judged qualitatively, correlated with the clinical success of ETV. The TVMI correlated with the qualitative assessments of displacement. Postoperative decrease in the TVMI occurred in the majority of successfully treated patients. Changes in third ventricular morphology preceded changes in other measures of third and lateral ventricular volume following ETV. Conclusions Assessment of third ventricular floor and lamina terminalis morphology is useful in predicting clinical success of ETV and in the follow-up in treated patients. The TVMI provided a quantitative assessment of the third ventricular morphology, which may be useful in equivocal cases and in research studies.

Ten year survival rates for patients with craniopharyngioma vary from 24 to 100%. A review of the database of all children diagnosed with craniopharyngioma in British Columbia (BC) revealed that several patients died >10 years after diagnosis. This retrospective study investigates the causes and timing of deaths and reports the overall survival in this population based group of patients. A chart review was conducted on all patients aged

OBJECTIVE To determine whether photo-protecting total parenteral nutrition in preterm infants influences arterial blood pressure differently according to gender. Blood pressure is influenced by complex mechanisms of vasomodulation. Oxidants are mediators and effectors in such reactions. Shielding total parenteral nutrition from light contributes to decrease the generation of peroxides. Girls may be better protected against an oxidant load than boys. We questioned whether shielding total parenteral nutrition may have cardiovascular effects that are influenced by gender. DESIGN A post hoc subgroup analysis of the effect of shielding parenteral nutrition from light. SETTING Neonatal intensive care unit. SUBJECTS Preterm infants

Objective [ ] The association of chorioamnionitis and non-cystic white matter injury, a common brain injury in premature newborns, remains controversial. Our objectives were to determine the association of chorioamnionitis and postnatal risk factors with white matter injury, and the effects of chorioamnionitis on early brain development, using advanced MR imaging. Methods [ ] Ninety-two preterm newborns (24-32 weeks gestation) were studied at a median age of 31.9 weeks and again at 40.3 weeks gestation. Histopathological chorioamnionitis and white matter injury were scored using validated systems. Measures of brain metabolism (N-acetylaspartate/choline and lactate/choline) on magnetic resonance spectroscopy, and microstructure (average diffusivity and fractional anisotropy) on diffusion tensor imaging were calculated from predefined brain regions. Results [ ] Thirty-one newborns (34%) were exposed to histopathological chorioamnionitis, and 26 (28%) had white matter injury. Histopathological chorioamnionitis was not associated with an increased risk of white matter injury (relative risk: 1.2; P=0.6). Newborns with postnatal infections and hypotension requiring therapy were at higher risk of white matter injury (P0.1). In contrast, white matter injury was associated with lower N-acetylaspartate/choline (–8.9%; P=0.009) and lower white matter fractional anisotropy (–11.9%; P=0.01). Interpretation [ ] Histopathological chorioamnionitis does not appear to be associated with an increased risk of white matter injury on magnetic resonance imaging or with abnormalities of brain development. In contrast, postnatal infections and hypotension are associated with an increased risk of white matter injury in the premature newborn. Final published version [ ] Ann Neurol. 2009 Aug;66(2):155-64. URL: http://www3.interscience.wiley.com/journal/76507645/home

Object Approximately 30% of children with posterior fossa tumors exhibit hydrocephalus after tumor resection. Recent literature has suggested that prophylactic endoscopic third ventriculostomy diminishes the risk of this event. Because the majority of patients will not have postoperative hydrocephalus, a preoperative clinical prediction rule that identifies patients at high or low risk for postresection hydrocephalus would be helpful to optimize the care of these children. Methods The authors evaluated a derivation cohort of 343 consecutive children with posterior fossa tumors who underwent treatment between 1989 and 2003. Multivariate methods were used on these data to generate the Canadian Preoperative Prediction Rule for Hydrocephalus. The rule's estimated risk of postresection hydrocephalus was compared with risk observed in 111 independent patients in the validation cohort. Results Variables identified as significant in predicting postresection hydrocephalus were age < 2 years (score of 3), papilledema (score of 1), moderate to severe hydrocephalus (score of 2), cerebral metastases (score of 3), and specific estimated tumor pathologies (score of 1). Patients with scores ≥ 5 were deemed as high risk. Predicted probabilities for the high- and low-risk groups were 0.73 and 0.25, respectively, from the derivation cohort, and 0.59 and 0.14 after prevalence adjustment compared with the observed values of 0.42 and 0.17 in the validation cohort. Conclusions A patient's score on the Preoperative Prediction Rule for Hydrocephalus will allow improved patient counseling and surgical planning by identifying patients at high risk of developing postresection hydrocephalus. These patients might selectively be exposed to the risks of preresection CSF diversion to improve outcome.

Detailed neurological, speech and language, psychological, and neuroimaging studies were carried out in eight children with the diagnosis of congenital ocular motor apraxia. The neurological examination showed clinical evidence of cerebellar vermis abnormality (hypotonia and truncal ataxia) in all cases. Neuroimaging studies suggested that the site of neuropathological disturbance of congenital ocular motor apraxia was the inferior vermis. Half of the subjects had associated speech apraxia. The most likely location of brain disturbance, which was responsible for the speech apraxia, was also an as yet undefined area of the vermis. Psychological testing consistently revealed visual-spatial difficulties. These may have been secondary to cerebellar pathology or to developmentally inappropriate sensory input caused by the abnormal saccades. Children with speech apraxia appear to be slightly more affected neurologically than those with normal speech.

Herpes simplex virus encephalitis in the newborn typically involves the cerebral cortex in a widespread manner. Herpes simplex virus type 2 rarely involves the brainstem. Here we report a 16-day-old infant with predominant brainstem and cerebellar involvement secondary to herpes simplex virus type 2 infection. Diffusion-weighted MRI performed 3 days after the onset of symptoms revealed restricted diffusion mainly in brainstem and cerebellar structures. No abnormal findings were seen on conventional MRI. Subsequent MRI scans showed evolution of the brain injury with extension along the corticospinal tracts. However, there was no evidence of any other supratentorial gray or white matter injury. This is the first report of predominant brainstem involvement in neonatal herpes simplex virus type 2 encephalitis. In addition, the importance of performing diffusion-weighted sequences to detect early central nervous system involvement and serial MRI to follow the evolution of central nervous system lesions is emphasized.

The precariousness of childhood in the developing world is most visible when the media spotlight falls on famine, natural disaster or civil war, but it casts a permanent shadow over family life in that world, as it did in Europe a hundred years ago. Premature death, life-threatening sickness, irreversible stunting of growth and the loss of a mother in childbirth are some of the most tangible evils of underdevelopment. Although poverty contributes to this dismal situation, many individual contingencies are avoidable to a substantial extent if people can be drawn into primary health-care systems that encourage them to exchange detrimental customs for better ideas of managing hygiene and parenthood.

Purpose: We sought to determine whether radiological evidence supports excyclorotation of the extraocular muscle cone as a cause of overelevation in adduction in children with craniosynostosis. Methods: This was a retrospective case series of 40 patients with craniosynostosis. Ophthalmic findings were assessed for incomitant vertical strabismus in particular excessive elevation in adduction. Computed tomography and magnetic resonance imaging scans were reviewed. Those scans with adequate coronal imaging of their orbits to assess the position and angulation of the horizontal extraocular muscles were identified, and the degree of rotation of the muscles formally measured along with aged matched controls. These groups were analyzed for the association between presence of overelevation in adduction and degree of excyclorotation of the extraocular muscle cone. Results: The identified updrift on adduction that mimics inferior oblique muscle overaction was present in 63% (25/40) of patients. Imaging that permitted accurate measurement of the muscles positions was available in 10 of the 40 patients. Of these 10, 8 had the updrift, and 7 of these 8 (88%) demonstrated more excyclorotation than their aged matched controls. Comparison of scan measurements of patients revealed a significant difference in degree of excyclorotation (mean difference = 16.2, 95% confidence interval 6.2–31.5; P = 0.006) between patients with and without excess elevation in adduction. Conclusion: Overelevation in adduction is significantly associated with excyclorotation of the extraocular muscle cone in children with craniosynostosis. We demonstrate a simple method to assess for the excyclorotation. Our findings support the importance of imaging of the orbits in these children before strabismus surgery.

The biomedical era started when laboratory science began to shape new ways of thinking about the causes of ill health. Within half a century, knowledge of nutrition and hygiene, together with the development of medicines of unprecedented efficacy, was making a decisive contribution to better health and life expectancy. The development of a profound understanding of inheritance and cellular organisation illuminated the origin of many kinds of human frailty, and provided powerful tools with which hitherto incurable diseases could be understood and perhaps cured. While biomedicine offers unprecedented opportunities to solve existing health problems, it also has the capacity to extend many of our biological capabilities. Will we be liberated or enslaved? The forces that drive and restrain this potential cultural evolution will be considered.

Trichothiodystrophy is a rare neuroectodermal disorder of autosomal recessive inheritance that is characterized by brittle hair, nail dysplasia, ichthyosis, mental retardation, and gonadal failure. We describe a female patient whose cranial MRI revealed almost total lack of myelination in the supratentorial white matter, which is similar to the previously described cases. In addition, there was progressive cerebellar and cerebral atrophy, which has not been well documented in association with trichothiodystrophy.

Idiopathic infantile arterial calcification is a rare and usually fatal disorder, which is characterized by widespread vaso-occlusive disease. Presentation is variable, but refractory hypertension is typical, with symptoms of cardiorespiratory failure. Some present in utero with evidence of fetal compromise, which may manifest as hydrops fetalis and premature delivery or stillbirth. Presentation otherwise is usually in the neonatal period with 85% of cases being fatal within the first 6 months. Coronary artery involvement is a poor prognostic feature. The pathophysiology of this disorder is well documented but the underlying etiology remains unknown. An autosomal recessive metabolic disorder is thought likely and this is supported in this case. Pulmonary hypertension has not previously been reported to be a primary feature of this disease. Here we describe such a case in which a newborn underwent extracorporeal membrane oxygenation, and during this time a diagnosis of idiopathic arterial calcification was made.

Now that transgenic strains of Xenopus laevis and X. tropicalis can be generated efficiently and with genomic sequence resources available for X. tropicalis, early amphibian development can be studied using integrated biochemical and genetic approaches. However, housing large numbers of animals generated during genetic screens or produced as novel transgenic lines presents a considerable challenge. We describe a method for cryopreserving Xenopus sperm that should facilitate low maintenance, long-term storage of male gametes. By optimising the cryoprotectant, the rates of cooling and thawing, and conditions for fertilisation, sperm from the equivalent of one-eighth of a X. laevis testis or of two X. tropicalis testes have been cryopreserved and used to fertilise eggs of both species after thawing. Sperm undergo a substantial loss of viability during a freeze-thaw cycle, but sufficient survive to fertilise eggs. Gametes of mutagenised frogs are being stored in connection with a screen for developmental mutations.

Background The frequent association between optic nerve hypoplasia (ONH) and other central nervous system abnormalities has been widely reported in the literature. Occasional reference has been made to arachnoid cyst as one of the associated findings. Method The charts and neuroradiologic findings of the 40 patients with ONH seen in our department as well as the Visually Impaired Program during the past 8 years were reviewed. Results An intracranial arachnoid cyst was present in 5 of the 40 patients (12.5%) with ONH and visual impairment. These patients' clinical and neuroradiologic findings are reported here. Conclusion The presence of an intracranial arachnoid cyst in a patient with hypoplastic optic nerves could occur as a coincidental association between these lesions. Alternatively, a common mechanism could give rise to both abnormalities. Three such possibilities—including damage to the developing visual pathway by the arachnoid cyst, absence of an axonal guidance molecule similar to netrin-1 identified in the mouse, or a common genetic mutation involving the myocillin gene causing both abnormalities—are considered.