Cognitive function in children with brain tumors in the first year after diagnosis compared to healthy matched controls.

BACKGROUND: Improved survival of children with brain tumors (BTs) has increased focus on ameliorating morbidity. To reduce the risk of progressive cognitive decline, remedial strategies need to be instituted early, based upon accurate appraisal of need, yet few studies have investigated cognition in BT children early post-diagnosis. The study aims were to investigate cognition in children with primary BTs 1, 6, and 12 months post-diagnosis compared with healthy children, exploring the impact of disease and treatment variables. METHODS: Forty-eight children aged 2-16 years with primary BTs, referred to a Regional Neurosurgical Unit over the 2-year study period were eligible for enrollment. The "best friends" model was used to recruit matched controls. Cognition was assessed using age-appropriate Wechsler Intelligence scales; Children's Memory Scale; Test of Everyday Attention for Children, and Wechsler Quicktest. RESULTS: Patients with BTs had significantly reduced performance compared to controls early post-diagnosis in tests of Performance IQ, processing speed, verbal and visual memory, and selective attention. Improved performance over 12 months was seen in patients with BTs although also, for some measures, in controls. Significant deficits in cognitive performance were seen one year post-diagnosis for Verbal IQ; processing speed, visual and verbal immediate memory, and selective attention. Infratentorial site, high tumor grade, hydrocephalus, radiotherapy, and chemotherapy were associated with poorer functioning. CONCLUSION: Early cognitive impairment is present in BT children, sometimes prior to radiotherapy/chemotherapy treatment, and is associated with hydrocephalus, high tumor grade and infratentorial site. Future studies should investigate the role of early rehabilitation in improving cognition.

Cortisol dynamics, quality of life and fatigue following traumatic brain injury in childhood.

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of acquired neurological morbidity. The prevalence of post-traumatic hypopituitarism (PTHP) and associated morbidity after childhood TBI is unclear. Our study investigated long term HPA (hypothalamus-pituitary-adrenal) axis function, in a prospective childhood TBI and control cohort, using measures of cortisol/cortisone secretion (physiological, stimulated), HPA axis feedback and exploring associations with fatigue, depression and Quality of Life (QoL) outcomes. METHODS: All TBI participants had data concerning severity and mechanism of TBI. All groups had clinical assessment, pituitary/brain MRI, questionnaire measures of QoL, fatigue, depression and salivary cortisone profiles including dexamethasone suppression test. In addition participants with Moderate/Severe TBI had ethical approval for baseline endocrine blood tests, overnight 12-hour venous sampling of cortisol and growth hormone, and stimulated HPA axis evaluation with an insulin tolerance test (ITT). RESULTS: Seventy-two participants with moderate/severe (n=31, age 19.8±4.2 years) or mild TBI (n=24, age 17.8±5.1 years) and matched controls (n=17, age 18.5±5.5 years) took part. Time post TBI was 6.8-10.8 years. Baseline endocrine tests confirmed normal thyroid and posterior pituitary function. One female with moderate/severe TBI had hypogonadism. Pituitary neuroimaging was normal in all participants. In 2/25 ITT and 9/22 overnight serum profiles peak cortisol was <500nmol/l. The two participants with suboptimal ITT cortisol response (392 and 483nmol/L) also had low peak spontaneous serum levels (227 and 447nmol/L respectively). Salivary cortisone profiles showed preservation of HPA axis circadian rhythm and suppression with dexamethasone in all but one TBI participant. TBI participants had higher morning salivary cortisone levels compared to controls. Fatigue was reported by 20/46 TBI participants but only 1/14 controls. Fatigue was not associated with stimulated (ITT) or spontaneous (overnight profile) cortisol, however one TBI participant with severe fatigue had a suboptimal ITT cortisol response. Specific QoL attributes of health state (cognition, memory) were impaired in TBI participants compared to controls. CONCLUSION: Although not as prevalent as previously reported, HPA axis dysfunction does occur in survivors of childhood TBI confirming the need for endocrine surveillance. However, in most of our paediatric TBI survivors assessed 7-11 years post-TBI, HPA function and circadian rhythmicity was preserved or had recovered. Chronic fatigue is a common concern post TBI but in the majority not associated with frank HPA axis dysfunction. Morning salivary cortisone levels were higher in TBI survivors, (who have a high prevalence of fatigue) compared to healthy controls, despite the recognised association of chronic fatigue with cortisol hyposecretion.

Nutritional blindness from avoidant-restrictive food intake disorder - recommendations for the early diagnosis and multidisciplinary management of children at risk from restrictive eating.

Avoidant-restrictive food intake disorder (ARFID) is an eating disorder characterised by limited consumption or the avoidance of certain foods, leading to the persistent failure to meet the individual's nutritional and/or energy needs. The disordered eating is not explained by the lack of available food or cultural beliefs. ARFID is often associated with a heightened sensitivity to the sensory features of different types of food and may be more prevalent among children with autism spectrum disorder (ASD) for this reason. Sight loss from malnutrition is one of the most devastating and life-changing complications of ARFID, but difficult to diagnose in young children and those with ASD who have more difficulty with communicating their visual problems to carers and clinicians, leading to delayed treatment and greater probability of irreversible vision loss. In this article, we highlight the importance of diet and nutrition to vision and the diagnostic and therapeutic challenges that clinicians and families may face in looking after children with ARFID who are at risk of sight loss. We recommend a scaled multidisciplinary approach to the early identification, investigation, referral and management of children at risk of nutritional blindness from ARFID.

Spinal cord arterio-venous malformations in children: a rare but important diagnosis.

Spinal cord arterio-venous malformations (AVMs) are rare and the diagnosis is often delayed or missed. We describe two cases presenting in different ways, as subarachnoid haemorrhage (SAH) or myelopathy. A catheter angiogram confirmed the diagnosis following which they were treated with coil occlusion or embolisation, or a combination of both, without any complications.

A detailed prospective longitudinal assessment of health status in children with brain tumors in the first year after diagnosis.

PURPOSE: To compare health status (HS) in children with brain tumors at 1 (t1), 6 (t6), and 12 (t12) months after diagnosis with "normal" controls. To assess the relationship between parent-report and self-report HS for patients at t12. METHODS: HS was assessed using the Health Utilities Index Mark III parent-report at all time points and self-report at t12. Twenty-nine patients and 32 controls were included in analysis of parent-report, and 21 patients and 22 controls in self-report HS at t12. Nonparametric analyses were used. RESULTS: Patients scored significantly lower than controls for global overall HS at all time points for parent-report and at t12 for self-report (Pmax=0.009). For parent-report, patients scored significantly lower than controls in the attributes of emotion, cognition, and pain at t1 and t6, in ambulation at t1 and in dexterity at t6. At t12, the difference was statistically significant for parent-report cognition only (all P<0.01). No attributes reached significance for self-report at t12. For patients, correlations between parent-report and self-report were good (rs>0.73) for all Health Utilities Index Mark 3 scores with the exception of emotion and pain. CONCLUSION: HS is significantly compromised in children with brain tumors over the first year after diagnosis, but improves with time. Parent-report and self-report differ, and both should be considered in assessing outcomes or defining interventions.

Child-related determinants of health-related quality of life in children with brain tumours 1 year after diagnosis.

OBJECTIVES: Infratentorial tumour site and health-related quality of life (HRQL) 1 month after diagnosis have been shown to predict HRQL 1 year after diagnosis in children with brain tumours. This study aimed to identify additional early child-related determinants of parent- and child-report HRQL. METHODS: Longitudinal prospective study. Semi-structured interviews took place approximately 1 and 12 months after diagnosis. HRQL was measured using the self- and parent-report Pediatric Quality of Life Scales (PedsQL 4.0) Total Scale Score and Health Utilities Index Mark 3 (HUI3) multi-attribute utility function. Child variables included performance and verbal IQ, general memory, selective attention executive function, behaviour problems, adaptive behaviour, symptoms of depression and anxiety and event related anxiety. Univariate analyses were used to identify potential early predictors of HRQL. Regression analysis was then used to identify the most important determinants of HRQL at 1 year. RESULTS: Thirty-five patients completed the 12-month interviews. Multivariate analysis showed infratentorial tumour site remained an important determinant of HRQL 1 year after diagnosis. Infratentorial tumour site and selective attention at 1 month generally best predicted poor self- and parent-report HRQL at 12 months. Adaptive behaviour and performance IQ may be important. CONCLUSION: Selective attention and infratentorial tumour site are most important in predicting both parent- and self-report HRQL at 1 year after diagnosis. Larger prospective studies are needed to confirm these findings. Cognitive remediation or/and pharmacological intervention, particularly aimed at children with infratentorial tumours may improve attention and subsequently HRQL and both merit further investigation.

Seizure management in children requiring palliative care: a review of current practice.

OBJECTIVES: Controlling seizures in children approaching death can be difficult, and there is a limited evidence base to guide best practice. We compared current practice against the guidance for seizure management produced by the Association of Paediatric Palliative Medicine (APPM). METHODS: Retrospective case note review of episodes of challenging seizure management in children receiving end-of-life care over a 10-year period (2006-2015) in the south-west region of England. RESULTS: We reviewed 19 admissions, in 18 individuals. Six (33%) had a malignancy, nine (50%) had a progressive neurodegenerative condition and three (17%) had a static neurological condition with associated epilepsy. Thirteen (72%) died in their local hospice, four (22%) at home, and one (6%) in hospital. Seventeen of 19 episodes involved the use of subcutaneous or intravenous midazolam infusion, for a mean of 11 days (range 3-27). There was a wide range of starting doses of midazolam, and 9/17 (53%) received final doses in excess of current dose recommendations. Six individuals received subcutaneous phenobarbital infusions, with four of these (67%) receiving final doses in excess of current dose recommendations. Plans for adjustments of infusion rates, maximal doses or alternative approaches should treatment fail were inconsistent or absent. In 16/18 (88%) cases seizures were successfully controlled prior to the day of the child's death. Staff found the experience of managing seizures at end of life challenging and stressful. CONCLUSIONS: Pharmacological approaches to seizure management in end-of-life care are variable, often exceeding APPM dose recommendations. Despite this, safe and effective seizure control was possible in all settings.

High frequency stimulation of the mamillothalamic tract for the treatment of resistant seizures associated with hypothalamic hamartoma.

We investigate the clinical outcome from stimulation of the mamillothalamic tract in two patients with intractable epilepsy secondary to hypothalamic hamartomas. One patient has a left-sided and the other a right-sided tumor. Both patients presented with a history of gelastic and complex partial seizures resistant to multiple antiepileptic drugs. Both patients underwent insertion of a single deep brain-stimulating electrode ipsilateral to the site of the tumor, lying adjacent to the mamillothalamic tract. Postoperatively they both had a significant reduction in seizure frequency, with one patient being seizure free for the last 10 months. An improvement in mood was reported by the patient's primary carers and demonstrated on quality of life questionnaires.

Family, demographic and illness-related determinants of HRQL in children with brain tumours in the first year after diagnosis.

AIMS: To evaluate the relationship between parent- and child-report Health-Related Quality of Life (HRQL) and demographic, tumour and family variables in children with a brain tumour in the first year after diagnosis and to identify determinants of HRQL at 12 months. PROCEDURE: Longitudinal prospective study: Semi-structured interviews took place approximately 1, 6 and 12 months after diagnosis. HRQL was measured using the self- and parent-report PedsQL 4.0 Total Scale Score. Tumour and treatment variables considered included tumour site and grade, hydrocephalus at diagnosis, chemotherapy and radiotherapy. Family variables included measures of family function, family support and family stress, the primary carer's coping strategies and symptoms of depression and anxiety. Univariate analyses were used at all three time points, and to identify potential early predictors of HRQL at 1 year. Regression analysis was then used to identify the most important determinants of HRQL at 1 year. RESULTS: Thirty-five patients completed the 12-month interviews. There were consistent significant negative correlations between concurrent family impact of illness and parent and self-report HRQL, and positive correlations between concurrent family support and parent-report HRQL. Treatment with radio- or chemotherapy correlated with child-report HRQL only at some time points. Multivariate analysis showed infratentorial tumour site, and poor HRQL at 1 month best predicted poor self- and parent-report HRQL at 12 months. CONCLUSION: Children with infratentorial tumours and poor HRQL early after diagnosis tend to have poor HRQL at 1 year. While family factors are important modulators of concurrent HRQL, they do not appear important in predicting HRQL.

Health related quality of life in the first year after diagnosis in children with brain tumours compared with matched healthy controls; a prospective longitudinal study.

This paper compares parent- and self-report health-related quality of life (HRQL) in children aged 2-16 years with brain tumours, one, six and twelve months after diagnosis with matched normal controls. HRQL was assessed using the PedsQL generic core scales. 37 tumour patients and 42 controls were included in analysis of parent-report, and 27 patients and 31 controls in self-report HRQL. Parent-report scores were significantly lower in patients than controls for all PedsQL scores at all time points (max p=0.002). Differences in self-report PedsQL between patients and controls were variable. The relationship between self- and parent-report in patients and controls was inconsistent; varied over time; and did not consistently correlate with parental depressive symptoms, suggesting parents and their children do not regard HRQL in a similar way. Prospective, longitudinal assessment of HRQL is important, but should be supplemented with other outcome measures such as health status and behaviour in this population.

A case report: Paediatric surfer's myelopathy.

Surfer's myelopathy was first described by Thompson et al., in 2004.1 It is a rare cause of sudden spinal cord injury that occurs in the absence of direct trauma to the spinal area in novice healthy surfers. We present the case of the youngest patient we are aware of to be diagnosed with surfer's myelopathy following actual surfing. A clear aetiology for surfer's myelopathy has not previous been described. However, the hypothesis that there is ischaemia to the lower spinal cord is supported by our case, where we present the first clear angiographic evidence of the occlusion of the great anterior radicular artery of Adamkiewicz in a patient diagnosed with surfer's myelopathy.

Severe progressive late onset myelopathy and arachnoiditis following neonatal meningitis.

This case series describes four children who had meningitis in the neonatal period. After a stable period of years, they developed a myelopathy caused by chronic arachnoiditis. The myelopathy was precipitated by a fall in two cases, and in two cases there was an acute deterioration after surgery. A history of neonatal meningitis should be taken into consideration before planning surgery or anaesthesia. Careful intra-operative positioning, immobilisation of the neck, and maintenance of blood pressure is important but may not prevent this complication.

Adrenalectomy further suppresses the NT-3 mRNA response to traumatic brain injury but this effect is not reversed with corticosterone.

Fluid percussion injury (FPI) and in situ hybridisation were used to evaluate the expression of NT-3 mRNA in the hippocampus after traumatic brain injury (TBI) in adrenal-intact and adrenalectomised rats (with or without corticosterone replacement). FPI and adrenalectomy independently significantly reduced the expression of NT-3 mRNA in the dentate gyrus (DG) and CA2 region. The effects of adrenalectomy in the CA2 region were partially reversed with corticosterone. In adrenalectomised animals undergoing FPI, a further significant decrease in NT-3 mRNA was observed in the DG, but this was not reversed by corticosterone. Glucocorticoids may, therefore, play a role in the basal regulation of NT-3 in the hippocampus, but the role of glucocorticoids in the modulation of the NT-3 response to TBI is unclear.

The King's Outcome Scale for Childhood Head Injury and injury severity and outcome measures in children with traumatic brain injury.

The aim of this study was to relate discharge King's Outcome Scale for Childhood Head Injury (KOSCHI) category to injury severity and detailed outcome measures obtained in the first year post-traumatic brain injury (TBI). We used a prospective cohort study. Eighty-one children with TBI were studied: 29 had severe, 15 moderate, and 37 mild TBI. The male:female ratio was 1.8:1. The mean age was 11 years 10 months (SD 3.6, range 5-16y). Discharge KOSCHI categories were good (n=34), moderate (n=39), severe (n=6), and unclassifiable (n=2). KOSCHI category correlated strongly with admission Glasgow Coma Score, length of hospital stay, and post-traumatic amnesia. It also correlated significantly with Verbal IQ and Performance IQ (Wechsler); measures of attention; health status (Health Utilities Index [HUI]); health-related quality of life (Pediatric Quality of Life Inventory [PedsQL]); depressive symptoms (Birleson Depression Scale) assessed within 3 months postTBI; and with Verbal IQ, selective attention (map mission), and HUI and PedsQL domains assessed at least 6 months post-TBI discharge. KOSCHI did not correlate with behaviour or executive function. We conclude that the KOSCHI scored at hospital discharge correlates with severity of injury and some cognitive, health status, and HRQL outcomes early after TBI. It is not helpful at predicting later difficulties, or behavioural and emotional problems.