Association between gut microbiota development and allergy in infants born during pandemic-related social distancing restrictions.

BACKGROUND: Several hypotheses link reduced microbial exposure to increased prevalence of allergies. Here we capitalize on the opportunity to study a cohort of infants (CORAL), raised during COVID-19 associated social distancing measures, to identify the environmental exposures and dietary factors that contribute to early life microbiota development and to examine their associations with allergic outcomes. METHODS: Fecal samples were sequenced from infants at 6 (n = 351) and repeated at 12 (n = 343) months, using 16S sequencing. Published 16S data from pre-pandemic cohorts were included for microbiota comparisons. Online questionnaires collected epidemiological information on home environment, healthcare utilization, infant health, allergic diseases, and diet. Skin prick testing (SPT) was performed at 12 (n = 343) and 24 (n = 320) months of age, accompanied by atopic dermatitis and food allergy assessments. RESULTS: The relative abundance of bifidobacteria was higher, while environmentally transmitted bacteria such as Clostridia was lower in CORAL infants compared to previous cohorts. The abundance of multiple Clostridia taxa correlated with a microbial exposure index. Plant based foods during weaning positively impacted microbiota development. Bifidobacteria levels at 6 months of age, and relative abundance of butyrate producers at 12 months of age, were negatively associated with AD and SPT positivity. The prevalence of allergen sensitization, food allergy, and AD did not increase over pre-pandemic levels. CONCLUSIONS: Environmental exposures and dietary components significantly impact microbiota community assembly. Our results also suggest that vertically transmitted bacteria and appropriate dietary supports may be more important than exposure to environmental microbes alone for protection against allergic diseases in infancy.

Posttraumatic stress disorder (PTSD) and complex PTSD in eating disorder treatment-seekers: Prevalence and associations with symptom severity.

Although childhood trauma and posttraumatic stress disorder (PTSD) have been well-researched in eating disorder epidemiology, prevalence rates are unavailable for complex PTSD (CPTSD). Under recently introduced ICD-11 criteria, individuals with CPTSD have both PTSD symptoms and additional disturbances in self-organization (DSO). Using ICD-11 criteria, this study aimed to determine the prevalence of PTSD and DSO symptoms, diagnostic rates of PTSD and CPTSD, and childhood trauma exposure in eating disorder treatment-seekers. Participants (N = 217) were individuals attending residential, partial hospitalization, and outpatient services who completed measures of eating disorder- and trauma-related symptoms and childhood adverse experiences. One third of participants reported PTSD symptoms, and over half reported DSO symptoms, with probable ICD-11 diagnostic rates of 3.8% for PTSD and 28.4% for CPTSD. CPTSD was significantly more prevalent than PTSD and more common in higher levels of care. Both PTSD and DSO symptom severity were positively correlated with eating disorder symptoms and impairment, rs = .285-.642. DSO symptom severity was a significant and unique explanatory factor of eating disorder severity and impairment. The findings highlight the prevalence of CPTSD in eating disorder populations and the association between DSO symptoms and eating psychopathology independent of PTSD symptoms. Implications are discussed for adjunct treatment approaches for individuals with comorbid eating disorders and PTSD or CPTSD.

Fifteen-minute consultation: Diagnosing serious pathology in children with headaches presenting to the emergency department.

Headache is one of the most common presentations to the paediatric emergency department. Although challenging, it is important to differentiate serious secondary headaches requiring emergency treatment from primary headache disorders. A detailed history and neurological examination can be used to identify children at higher risk of serious underlying pathology. Neuroimaging decisions should be taken carefully, weighing risk versus benefit in each case. This article will discuss five patient scenarios highlighting red flags and differential diagnoses in children presenting with headache in the emergency department.

Pediatric Ischemic Stroke: An Infrequent Complication of SARS-CoV-2.

OBJECTIVE: Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS-CoV-2 is unknown. This study aimed to determine the proportion of pediatric SARS-CoV-2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS-CoV-2 in the first 3 months of the pandemic in an international cohort. METHODS: We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS-CoV-2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS-CoV-2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS-CoV-2 from March 1 to May 31, 2020. RESULTS: Of 42 centers with SARS-CoV-2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS-CoV-2 had ischemic strokes. Proportions of stroke cases positive for SARS-CoV-2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS-CoV-2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS-CoV-2. Seven of 8 patients with SARS-CoV-2 had additional established stroke risk factors. INTERPRETATION: As in adults, pediatric stroke is an infrequent complication of SARS-CoV-2, and SARS-CoV-2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS-CoV-2 in pediatric stroke better, SARS-CoV-2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021;89:657-665.

Is guided self-help family-based treatment for parents of adolescents with anorexia nervosa on treatment waitlists feasible? A pilot trial.

OBJECTIVE: The aim of the study was to assess the feasibility (recruitment and retention) of an online 12-session guided self-help family-based treatment (GSH-FBT) for families on the waitlist for face-to-face FBT utilizing trainee psychologists to assist carers of children with anorexia nervosa (AN) or atypical AN. METHOD: The primary outcomes were feasibility of GSH-FBT for families on the waitlist and secondary exploratory outcomes examined improvement of child and parental function. RESULTS: Of 187 eligible families on the waitlist, 24 (13%) expressed interest in the study; 16 (67%) of these families completed baseline, 13 (54%) completed GSH-FBT over a 6-month recruitment period. Children (mean age = 13.92, SD = .86; mean body mass index [BMI] centile = 29.47, SD = 24.80) had an average weight gain of 6 kg (BMI centile effect size = 2.61, 95% CI: 1.77-3.44) and a decrease in eating disorder behaviors (effect size = 1.11, 95% CI: .27-1.95). Improvements also occurred for general mood and behaviors in the child, and the impact of eating disorder symptoms on their functioning. Parents reported improvements in knowledge, skills, and confidence in managing AN. DISCUSSION: Use of this low-cost intervention while families are on the waitlist for FBT is engaging and useful but strategies to improve initial recruitment are needed. PUBLIC SIGNIFICANCE STATEMENT: Although most eligible families did not enroll in an online 12-session guided self-help family-based treatment for families on the waitlist for face-to-face FBT for anorexia nervosa, families who participated found it engaging. The children experienced improvements in BMI centile, eating and behavior. Parents reported increased confidence, knowledge, and skills. We need to examine how families can be encouraged to participate on online training when on waitlists for treatment.

Understanding treatment delay: Perceived barriers preventing treatment-seeking for eating disorders.

OBJECTIVE: Only a small proportion of individuals with an eating disorder will receive targeted treatment for their illness. The aim of this study was to examine the length of delay to treatment-seeking and determine the barriers preventing earlier access and utilisation of eating disorder treatment for each diagnostic group - anorexia nervosa, bulimia nervosa, binge eating disorder and other specified feeding or eating disorder. METHOD: Participants were recruited as part of the TrEAT multi-phase consortium study. One hundred and nineteen Australians (13-60 years; 96.9% female) with eating disorders currently accessing outpatient treatment for their illness completed an online survey comprised of self-report measures of eating disorder severity, treatment delay and perceived barriers to treatment-seeking. The treating clinician for each participant also provided additional information (e.g. body mass index and diagnosis). RESULTS: Overall, the average length of delay between onset of eating disorder symptoms and treatment-seeking was 5.28 years. Controlling for age, latency to treatment-seeking was significantly longer for individuals with bulimia nervosa and binge eating disorder compared to anorexia nervosa. However, when perceived barriers to treatment-seeking were investigated, there were no significant differences between the diagnostic groups in regard to the perceived barriers they experienced. Stigma was rated as the most impactful barrier for each diagnostic group. CONCLUSION: Findings suggest that individuals with eating disorders face substantial delays in accessing appropriate treatment and that latency to treatment-seeking is often magnified for counter-stereotypical eating disorder presentations. Further research is required to investigate other factors contributing to this delay.

Precision therapy in the genetic epilepsies of childhood.

Despite recent advances in both the understanding and treatment of the epilepsies, the rate of refractory epilepsy has remained static for many years. However, given our greater understanding of the aetiology and genetic basis of many paediatric and adult epilepsies, there is now scope to expand treatment. In this review, we discuss the current and potential use of precision medicine in the genetic epilepsies of childhood. We will discuss how optimal control and a reduction in the rate of refractory seizures using targeted therapy could be developed and assessed. We propose a six-tier approach to defining precision therapeutics in epilepsy and discuss how this can be incorporated into a clinical trial design. The lower tiers (1-2) represent therapies in common usage that we know work for certain epilepsy syndromes but do not precisely target the underlying problem. They work to reduce seizures but do not directly or effectively attenuate the developmental phenotype. The higher tiers (5-6) are currently purely speculative and look to a future with highly disease-specific therapies based on correction of underlying genomic and proteomic issues. In order to achieve this, scientists will have to embark on a 'whole-omic' approach to understand the underlying pathophysiology in order to design a precision therapy. What this paper adds Epilepsy treatment is classified into six tiers depending on how precisely the mechanism of action addresses the aetiology. Tier 1 treatment is based on the historical response of certain epilepsy phenotypes to specific medication. Tier 6 concerns therapy targeting genes and networks that rescue the whole phenotype. Clinical trial infrastructure and population-based disease registries are necessary so that patients can participate in trials for novel precision therapies.

CHD2-Related CNS Pathologies.

Epileptic encephalopathies (EE) are severe epilepsy syndromes characterized by multiple seizure types, developmental delay and even regression. This class of disorders are increasingly being identified as resulting from de novo genetic mutations including many identified mutations in the family of chromodomain helicase DNA binding (CHD) proteins. In particular, several de novo pathogenic mutations have been identified in the gene encoding chromodomain helicase DNA binding protein 2 (CHD2), a member of the sucrose nonfermenting (SNF-2) protein family of epigenetic regulators. These mutations in the CHD2 gene are causative of early onset epileptic encephalopathy, abnormal brain function, and intellectual disability. Our understanding of the mechanisms by which modification or loss of CHD2 cause this condition remains poorly understood. Here, we review what is known and still to be elucidated as regards the structure and function of CHD2 and how its dysregulation leads to a highly variable range of phenotypic presentations.

Outpatient therapy for adult anorexia nervosa: Early weight gain trajectories and outcome.

OBJECTIVE: The purpose of the study was to identify latent classes of trajectory of change in body mass index (BMI) between the initial and thirteenth session of outpatient treatment for adult anorexia nervosa and identify the association with outcome. METHOD: Participants (n = 120) were randomised to one of three outpatient therapies. RESULTS: Four latent classes were identified; two classes (higher, rapid and higher, moderate) had BMI > 17 kg/m2 at initial assessment, and both gained significantly more weight over the 13 sessions compared to the other two classes. The third and fourth classes (middle, stable and low, stable) had an initial BMI of 16.44 and 15.31, respectively, and neither gained weight over the first 13 sessions. Compared to the other three classes, the higher, rapid class (N = 19, 16%) showed a significantly greater BMI increase over the first 13 sessions of therapy and a significantly higher rate of remission at end of treatment and 12-month follow-up (18-22 months post-randomisation). CONCLUSIONS: The group with the greatest early weight gain had significantly higher levels of remission. Higher BMI at baseline without substantial early weight gain was insufficient to produce higher levels of remission than those with lower weight at baseline.

Circulating epigenetic biomarkers for detection of recurrent colorectal cancer.

BACKGROUND: The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence. METHODS: Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched-chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc-finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold). RESULTS: The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%-69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%-36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%-99.6%; CEA, 96.4%; 95% CI, 91.4%-99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9-1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3-20.6; P = .407). CONCLUSIONS: The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.

Very-late-onset Friedreich's ataxia: diagnosis in a kindred with late-onset cerebellar ataxia.

Friedreich's ataxia is classically considered a disease with onset in the first or second decade. However, late-onset (age of onset 25-39 years) and very-late-onset (age of onset >40 years) forms do occur rarely. Misdiagnosis is common, particularly because the later onset forms of Friedreich's ataxia commonly do not show characteristic features of the disorder (areflexia, dysarthria, sensory neuropathy, extensor plantars, amyotrophy, cardiac involvement, diabetes mellitus, scoliosis). Also, there may be atypical features such as spasticity, brisk reflexes and laryngeal dystonia. We present the clinical, imaging and genetic findings of a kindred with very-late-onset Friedreich's ataxia and discuss the pitfalls and risk of misdiagnosis.

Low Sensitivity of Fecal Immunochemical Tests and Blood-Based Markers of DNA Hypermethylation for Detection of Sessile Serrated Adenomas/Polyps.

BACKGROUND: Early detection and removal of precursor lesions reduce colorectal cancer morbidity and mortality. Sessile serrated adenomas/polyps (SSP) are a recognized precursor of cancer, but there are limited studies on whether current screening techniques detect this pathology. AIMS: To investigate the sensitivity of fecal immunochemical tests (FIT) and epigenetic biomarkers in blood for detection of SSP. METHODS: A prospective study offered FIT and a blood test (Colvera for methylated BCAT1 and IKZF1) to adults referred for colonoscopy. Sensitivity of FIT and the blood test were determined for four types of pathology: low-risk conventional adenoma, high-risk adenoma, SSP, and absence of neoplasia. Comparisons were made for FIT positivity at 10 and 20 µg hemoglobin (Hb)/g feces. RESULTS: One thousand eight hundred and eighty-two subjects completed FIT and underwent colonoscopy. One thousand four hundred and three were also tested for methylated BCAT1/IKZF1. The sensitivity of FIT (20 µg Hb/g feces) for SSP was 16.3%. This was lower than the sensitivity for high-risk adenomas (28.7%, p < 0.05), but no different to that for low-risk adenomas (13.1%) or no neoplasia (8.4%). A positive FIT result for SSP was not associated with demographics, morphology, concurrent pathology or intake of medications that increase bleeding risk. FIT sensitivity for SSP did not significantly increase through lowering the positivity threshold to 10 µg Hb/g feces (20.4%, p > 0.05). Sensitivity of the blood test for SSP was 8.8%, and 26.5% when combined with FIT. CONCLUSIONS: Both FIT and blood-based markers of DNA hypermethylation have low sensitivity for detection of SSP. Further development of sensitive screening tests is warranted.

Antiapoptotic serine protease inhibitors contribute to survival of allergenic TH2 cells.

BACKGROUND: The mechanisms that regulate maintenance of persistent TH2 cells and potentiate allergic inflammation are not well understood. OBJECTIVE: The function of serine protease inhibitor 2A (Spi2A) was studied in mouse TH2 cells, and the serine protease inhibitor B3 (SERPINB3) and SERPINB4 genes were studied in TH2 cells from patients with grass pollen allergy. METHODS: Spi2A-deficient TH2 cells were studied in in vitro culture or in vivo after challenge of Spi2A knockout mice with ovalbumin in alum. Expression of SERPINB3 and SERPINB4 mRNA was measured in in vitro-cultured TH2 cells and in ex vivo CD27-CD4+ cells and innate lymphoid cell (ILC) 2 from patients with grass pollen allergy by using quantitative PCR. SERPINB3 and SERPINB4 mRNA levels were knocked down in cultured CD27-CD4+ cells with small hairpin RNA. RESULTS: There were lower levels of in vitro-polarized TH2 cells from Spi2A knockout mice (P < .005) and in vivo after ovalbumin challenge (P < .05), higher levels of apoptosis (Annexin V positivity, P < .005), and less lung allergic inflammation (number of lung eosinophils, P < .005). In vitro-polarized TH2 cells from patients with grass pollen allergy expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P < .05) compared with unpolarized CD4 T cells. CD27-CD4+ from patients with grass pollen allergy expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P < .0005) compared with CD27+CD4+ cells. ILC2 expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P < .0005) compared with ILC1. Knockdown of either SERPINB3 or SERPINB4 mRNA (both P < .005) levels resulted in decreased viability of CD27-CD4+ compared with control transduced cells. CONCLUSION: The Serpins Spi2A in mice and SERPINB3 and SERPINB4 in allergic patients control the viability of TH2 cells. This provides proof of principle for a therapeutic approach for allergic disease through ablation of allergic memory TH2 cells through SERPINB3 and SERPINB4 mRNA downregulation.

The Temple Star Transitional Model of Care for epilepsy; the outcome of a quality improvement project.

OBJECTIVE: The aim and objective of this study was to assess the knowledge and views of parents on transitional and adolescent care in young adults with epilepsy, and to develop a transitional and adolescent program for epilepsy. METHODS: Data were collected from questionnaires completed by parents during focus groups exploring transitional care and inherent issues for young adults, aged 12-18years, with epilepsy. The questionnaire assessed the current knowledge and views of parents of children with epilepsy on transitional care, and following a presentation on "Transition in Epilepsy" (including themes such as self-advocacy, independent healthcare behavior, sexual health, psychosocial support, educational and vocational planning, health and lifestyle issues) assessed feedback on the proposed model of care in transitional and adolescent care. RESULTS: Data were collected from 34 parents; the majority of parents, 74% (n=25), wish their children to be transitioned and transferred over to the adult epilepsy sites at the age of 18years. Over 82% (n=28) of parents believe the concept of transition should be introduced between the ages of 12-16years. CONCLUSION: This quality improvement initiative identified the need for transitional care to begin at an early age. This study engaged parents in a process to improve adolescent and transitional care for adolescents with epilepsy. This study also highlights the importance of introducing a detailed preparatory phase for a transitional and adolescent care in epilepsy.

Randomized controlled psychotherapy trials in eating disorders: Improving their conduct, interpretation and usefulness.

BACKGROUND: While randomized controlled trials (RCTs) inform the efficacy and effectiveness of treatments, we need to understand that even RCTs can be associated with sub-optimal execution. This is of special pertinence to eating disorders given the majority of treatment studies involving cognitive behaviour therapy are of poor quality with respect to managing risk of bias adequately. METHODS: The current paper outlines the components of a good RCT for psychotherapy, and examines ways to improve the conduct, interpretation, and usefulness of RCTs. RESULTS: This includes managing reporting bias, recognizing the limits of randomization, applicability, and ethical considerations. CONCLUSIONS: We highlight a number of strategies for future research, including issues related to utilizing a variety of designs to examine treatment outcomes, integrity, openness and reproducibility.

A single session assessment and psychoeducational intervention for eating disorders: Impact on treatment waitlists and eating disorder symptoms.

OBJECTIVE: Long waitlists are common in eating disorder services and can have a detrimental impact on patients. We examined the effect on waitlist length, attendance, and eating disorder symptoms, of a 75-90 min single session intervention (SSI), attended a median of 16 days after referral to a specialist eating disorders clinic. METHOD: Sequential referrals (N = 448) to a public outpatient eating disorders program were tracked from referral until a decision was made on patients entering treatment. One group ("SSI cohort") received a protocol incorporating assessment and psychoeducation about eating disorders before being placed on a waitlist, after which they received further assessment and entered treatment. Data on patient flow indices were collected from this cohort and compared to data from a "Pre-SSI" cohort who had not received the SSI. Symptom change was examined in the SSI cohort. RESULTS: Waitlist length reduced and the proportion of referrals attending assessment and being allocated to treatment increased. Eating disorder symptoms and impairment decreased. Underweight patients (Body Mass Index [BMI] < 18.5 kg/m2 ) gained weight. DISCUSSION: These findings suggest that a single session psychoeducational assessment may reduce waiting times, increase the likelihood of patients entering treatment, and facilitate early reductions in eating disorder symptoms. However, there may be other explanations for the changes observed.

Autopsy findings in EPG5-related Vici syndrome with antenatal onset.

Vici syndrome is one of the most extensive inherited human multisystem disorders and due to recessive mutations in EPG5 encoding a key autophagy regulator with a crucial role in autophagosome-lysosome fusion. The condition presents usually early in life, with features of severe global developmental delay, profound failure to thrive, (acquired) microcephaly, callosal agenesis, cataracts, cardiomyopathy, hypopigmentation, and combined immunodeficiency. Clinical course is variable but usually progressive and associated with high mortality. Here, we present a fetus, offspring of consanguineous parents, in whom callosal agenesis and other developmental brain abnormalities were detected on fetal ultrasound scan (US) and subsequent MRI scan in the second trimester. Postmortem examination performed after medically indicated termination of pregnancy confirmed CNS abnormalities and provided additional evidence for skin hypopigmentation, nascent cataracts, and hypertrophic cardiomyopathy. Genetic testing prompted by a suggestive combination of features revealed a homozygous EPG5 mutation (c.5870-1G>A) predicted to cause aberrant splicing of the EPG5 transcript. Our findings expand the phenotypical spectrum of EPG5-related Vici syndrome and suggest that this severe condition may already present in utero. While callosal agenesis is not an uncommon finding in fetal medicine, additional presence of hypopigmentation, cataracts and cardiomyopathy is rare and should prompt EPG5 testing.

Clinical presentation and prognostic indicators in 100 adults and children with neurofibromatosis 1 associated non-optic pathway brain gliomas.

Type 1 Neurofibromatosis (NF1) is a common autosomal dominant condition, with a major impact on the nervous system, eye, bone, and skin, and a predisposition to malignancy. At present it is not possible to predict clinically or on imaging, whether a brain tumour will remain indolent or undergo high-grade change. There are no consensus guidelines on the follow-up of non-optic pathway glioma (non-OPG) tumours in NF1. One hundred patients from the National NF1 Service with generalised NF1 and a diagnosis of non-OPG glioma were followed up for a median time of 63 months after glioma detection. Forty-two patients underwent surgical intervention. Ninety-one percent (38) of those requiring surgery did so within 5 years of diagnosis of glioma. Serial neuroimaging was undertaken in 88 patients. In 66 (75%), the lesion on the scan was stable or had improved at follow-up. High-grade lesions were present in five patients and were strongly associated with tumours in the thalamus (p = 0.001). Five patients died during follow-up. The diagnosis of high-grade glioma had a HR of 99.7 (95% CI 11.1-898.9, p < 000.1) on multivariate Cox regression to evaluate predictive factors related to death. In our cohort of 100 patients with NF1, we have shown that tumours in the thalamus are more likely to be associated with radiological progression, high-grade tumours, and surgical intervention. As a result of this finding, heightened surveillance with more frequent imaging should be considered in thalamic involvement. We have also demonstrated that over 40% of patients underwent surgery, and did so within 5 years of tumour diagnosis. Serial imaging should be undertaken for at the very least, 5 years from tumour detection.