Effect of high-endurance exercise intervention on sleep-dependent procedural memory consolidation in individuals with schizophrenia: a randomized controlled trial.

BACKGROUND: Little is known about the effects of physical exercise on sleep-dependent consolidation of procedural memory in individuals with schizophrenia. We conducted a randomized controlled trial (RCT) to assess the effectiveness of physical exercise in improving this cognitive function in schizophrenia. METHODS: A three-arm parallel open-labeled RCT took place in a university hospital. Participants were randomized and allocated into either the high-intensity-interval-training group (HIIT), aerobic-endurance exercise group (AE), or psychoeducation group for 12 weeks, with three sessions per week. Seventy-nine individuals with schizophrenia spectrum disorder were contacted and screened for their eligibility. A total of 51 were successfully recruited in the study. The primary outcome was sleep-dependent procedural memory consolidation performance as measured by the finger-tapping motor sequence task (MST). Assessments were conducted during baseline and follow-up on week 12. RESULTS: The MST performance scored significantly higher in the HIIT (n = 17) compared to the psychoeducation group (n = 18) after the week 12 intervention (p < 0.001). The performance differences between the AE (n = 16) and the psychoeducation (p = 0.057), and between the AE and the HIIT (p = 0.999) were not significant. Yet, both HIIT (p < 0.0001) and AE (p < 0.05) showed significant within-group post-intervention improvement. CONCLUSIONS: Our results show that HIIT and AE were effective at reverting the defective sleep-dependent procedural memory consolidation in individuals with schizophrenia. Moreover, HIIT had a more distinctive effect compared to the control group. These findings suggest that HIIT may be a more effective treatment to improve sleep-dependent memory functions in individuals with schizophrenia than AE alone.

Spondylodiscitis following ingestion of button battery in an infant-a case-based update.

Button battery ingestion in infants is an increasingly common surgical emergency which can lead to oesophageal perforation, mediastinitis, trachea-oesophageal fistulation, airway compromise and death. One exceedingly rare complication of battery ingestion is discitis and osteomyelitis in the cervical and upper thoracic spine. Diagnosis is normally delayed due to the non-specific presentation, delayed imaging findings and the initial clinical focus on dealing with the immediate, and potentially life-threatening, complications. We describe a case of a 1-year-old girl who presented with haematemesis and an oesophageal injury, secondary to button battery ingestion. Sagittal reconstruction of the CT chest demonstrated a suspicious area of vertebral erosion in the cervicothoracic spine which prompted a further evaluation with MRI demonstrating spondylodiscitis of C7-T2 with vertebral erosion and collapse. The child was successfully treated with long course of antibiotics. We wish to highlight the importance of clinical and radiological spinal assessment in children with button battery ingestion to avoid delayed diagnosis and complications of spinal osteomyelitis.

The role of surgery in relieving calcified shunt site-related pain in patients with functioning VP shunt.

PURPOSE: Shunt calcification is a known late sequela of ventriculoperitoneal (VP) shunt insertion and is associated with shunt malfunction. However, in some patients, while shunt functionality is preserved despite calcification of the catheters, they experience nociceptive symptoms. In this paper, the authors present their surgical experience in managing patients with a functional VP shunt and experiencing pain secondary to shunt calcification. METHODS: We analysed outcomes of patients presenting with pain at the level of a calcified shunt who underwent surgical untethering of the calcified catheter from the soft tissues. This procedure was commenced by the senior author in 2015. Patients were collected prospectively from the databases of two institutions. Evidence of shunt calcification was confirmed on neuroimaging. RESULTS: Seven patients, two male and five female, were included. The mean age at untethering was 13.5 years. The mean time interval between primary shunt surgery and symptom onset was 12 years (range 6-16 years). The commonest site of tethering was the neck (50%) followed by abdomen and chest (both 25%). Six patients underwent untethering of the catheter from soft tissues. One patient had removal of a redundant segment of calcified shunt left in situ during a previous revision. All patients experienced pain relief following shunt untethering. CONCLUSION: Untethering of calcified VP shunt catheters from soft tissue can be considered an effective treatment of shunt site pain and offered to patients presenting with a functional VP shunt.

Clinical features and outcome in pediatric arteriovenous malformation: institutional multimodality treatment.

PURPOSE: Intracranial arteriovenous-malformation (AVM) is a relatively rare condition in pediatrics, yet is a major cause of spontaneous intracranial hemorrhage with a risk of fatal hemorrhage reported to be between 4 and 29%. Little is known about vessel morphology and optimum treatment modalities including multimodality combination therapy and prognosis in children. METHODS: A retrospective review of all children presenting to our institution from 2006 to 2020 that had an AVM was undertaken. RESULTS: A total of 50 children were identified with median age of 11 (range 1-16) years. The mean follow-up was 7.6 years. Forty-one children presented as an emergency and of those, 40 had hemorrhage identified on initial brain imaging. The average nidus size was 25 mm, drainage was superficial in 51% of cases, and located in eloquent cortex in 56%. The supplemental Spetzler-Martin grading indicated 78% (39/50) were grade 4 and above (moderate to high risk). Primary treatment modalities included embolization in 50% (25) or SRS in 30% (15) and surgery in 20% (10).The AVM was obliterated on follow-up DSA in 66% children. Three children had post-treatment hemorrhage, two related to embolization and one the day following SRS, giving a re-bleed rate of 6%. The GOSE was available for 32 children at long term follow and 94% had a good outcome (GOSE 5-8). Two children died due to acute hemorrhage (4%). CONCLUSION: The majority of children with AVM present with hemorrhage. The rebleed rate during definitive treatment is low at 6% over the study period. The selective use of the 3 modalities of treatment has significantly reduced mortality and severe disability.

Molecular subgroup of medulloblastoma: evaluation of contribution to CSF diversion following tumour resection.

INTRODUCTION: Medulloblastoma is the commonest malignant brain tumour in children. Pre-operative hydrocephalus is present in up to 90% of these patients at presentation. Following posterior fossa surgery, despite resolution of fourth ventricular obstruction, a proportion of these children will still require cerebrospinal fluid (CSF) diversion for management of persistent or new hydrocephalus. Various scoring systems have been developed to predict the risk for CSF diversion following posterior fossa surgery. However, no accurate tool exists regarding which pathological subset or group of medulloblastoma patients will require a shunt post-operatively. In this study we investigated the impact of molecular subgroup of medulloblastoma on shunt dependency post-operatively in paediatric patients. METHODS: We undertook a retrospective multi-centre study of children with medulloblastoma who underwent tumour resection. Those with available molecular subgroup were identified. Demographic data and clinical parameters including age, sex, presence of pre-operative hydrocephalus, extent of surgical resection, evidence of metastasis/leptomeningeal disease and need for CSF diversion post-operatively were further analysed. RESULTS: Sixty-nine children with medulloblastoma with available molecular data were identified during the study period with male to female ratio of 1.5:1 (42M:27F). Twelve patients (17.4%) belonged to SHH, 10 (14.5%) Wnt, 19 (27.5%) Group 3 and 15 (21.7%) Group 4; 13 (18.8%) were non-specified Group 3 or 4. A total of 18 (26%) patients had evidence of leptomeningeal disease at presentation (20% of Wnt, 42% of Group 3, 33% of group 4, 23% of group 3/4, and 0% of SHH). Fifteen patients (22%) underwent post-operative ventriculoperitoneal (VP) shunt insertion. No patient in the Wnt group required ventriculoperitoneal (VP) shunt post-operatively in this cohort. Need for shunt was associated with pre-operative hydrocephalus, leptomeningeal disease, with molecular group 3 or 4 demonstrating higher rate of leptomeningeal disease, and pre-operative hydrocephalus. Age, extent of resection and pre-operative EVD were not associated with need for shunt in this cohort. Regression analysis identified only pre-operative hydrocephalus and leptomeningeal disease as independent predictors of need for shunt post-resection in this cohort. CONCLUSION: All patients requiring permanent post-operative VP shunt belonged to non-Wnt groups, particularly group 3 and 4. Although medulloblastoma subgroup does not independently predict need for post-operative shunt, presence of leptomeningeal disease and pre-operative hydrocephalus, and their higher prevalence in group 3 and 4, likely account for observed higher rate of shunting in these groups.

Optic Nerve Germinoma and Transient Spontaneous Regression-More Than Meets the Eye.

Infiltration of the optic pathway by germ cell tumors is exceptional and can lead to confusion with glioma or inflammatory conditions. We present the case of a 14-year-old girl with an optic nerve germinoma extending to the hypothalamus and manifesting as panhypopituitarism and visual loss. The patient experienced spontaneous regression of the lesion followed by secondary deterioration requiring treatment. Four other cases of spontaneously regressing intracranial germinoma followed by regrowth have been reported in the literature. This report highlights the importance of clinical and radiologic monitoring of intracranial germinoma, even in the event of initial spontaneous improvement.

A rare case of inferior vena cava occlusion secondary to abdominal pseudocyst associated with ventriculoperitoneal shunt-case report and review of literature.

BACKGROUND AND IMPORTANCE: Abdominal pseudocyst (APC) is an uncommon but well-recognised complication of ventriculo-peritoneal (VP) shunt. Diagnosis is based on clinical features of shunt malfunction, including headaches, vomiting and drowsiness, and abdominal swelling. APCs can grow to large sizes resulting in compression of abdominal viscera; however, inferior vena cava (IVC) compression is extremely rare, and only one other case associated with VP shunt had been reported. CLINICAL PRESENTATION: We report a case of a 12-year-old girl with a background of open myelomeningocoele repair, kyphoscoliosis and right-sided VP shunt in situ who presented with bilateral lower limb swelling and abdominal distension. She exhibited no features of raised intracranial pressure but had bilateral pitting oedema up to the groin. Abdominal ultrasound and CT scan showed a massive septated pseudocyst (20 × 18 × 8 cm) compressing the IVC. The APC was drained, and the shunt was externalised, with conversion to a ventriculo-atrial (VA) shunt 1 week later after cultures of the cystic fluid, cerebrospinal fluid and shunt tube came back sterile. The patient remained well with no recurrence of the abdominal fluid and no VA shunt complication at 36-month follow-up. CONCLUSION: This patient had specific risk factors for development of a massive APC and the subsequent IVC compression, including prior surgeries, spinal deformity, abnormal abdominal anatomy and poor abdominal muscle tone and sensation. Early recognition of this complication and prompt alleviation of the mass effect of IVC compression can prevent long-term neurological and vascular sequalae.

Seizure improvement following vagus nerve stimulator (VNS) battery change with cardiac-based seizure detection automatic stimulation (AutoStim): early experience in a regional paediatric unit.

PURPOSE: The recent VNS models (AspireSR® Model 106, SenTiva™ Model 1000 (VNS Therapy®, LivaNova)) include a new function of cardiac-based seizure detection (CBSD) automatic stimulation, known as 'AutoStim'. This algorithm uses tachycardia as a proxy to a seizure, and the battery delivers a closed-loop electrical current in addition to its programmed stimulation. This function leads to further seizure reduction in adults, but this advantage has not been reported in the paediatric population. This study aims to investigate whether battery change with AutoStim leads to further seizure reduction in children. METHODS: This observational study included the first 10 cases of VNS battery change from non-AutoStim to AutoStim function. During the battery change operation, the new VNS was switched on, with the same normal and magnet mode settings as the previous VNS. The AutoStim mode was activated at the same time. Data on seizure burden were collected at 3 time points: (1) before the first VNS insertion, (2) before battery replacement (post-1st VNS) and (3) 12 months post-battery change (post-AutoStim). The net effect of AutoStim, the only changed parameter, was evaluated by comparing the seizure burden prior to and 12 months following battery change in each child. RESULTS: The seizure reduction improved significantly from 60 to 83% following battery change with AutoStim. Categorising the outcome according the McHugh classification, children achieving class I and II outcome (≥ 50% seizure reduction) improved from 70 to 90%. CONCLUSION: This is the first study to demonstrate the additional efficacy of AutoStim in children treated with VNS.

Chyloperitoneum following open myelomeningocele repair: dealing with an extremely rare finding.

PURPOSE: Chyloperitoneum is an extremely rare finding following myelomeningocele (MMC) repair in neonates. We aimed to describe the characteristics of such a case and explore its clinical significance. CASE REPORT: A male baby born at term with open MMC and hydrocephalus underwent MMC repair surgery with rotational flaps on the first postnatal day. The procedure was uneventful. Three days later, he underwent a right ventriculoperitoneal shunt (VPS) insertion. On opening the peritoneum, a remarkable amount of yellowish opaque fluid was observed. Chyloperitoneum was suspected, but the VPS procedure was completed as planned. Biochemical analysis was consistent with that of chyle. DISCUSSION: Neonatal chylous ascites is a rare condition; hence, available data on pathophysiology and therapy in the literature are scarce. It is postulated that the MMC repair in neonates causes abdominal tautness, which leads to rupture of small lymphatics and raised intraportal pressure. The combination of these two processes results in extravasation of chyle from the gastrointestinal tract. Presence of chyloperitoneum is not a contraindication for VPS insertion. CONCLUSION: Chyloperitoneum is an extremely rare sequela of MMC repair in neonates. Pediatric neurosurgeons should be aware of it, especially when a VPS procedure is to follow a repair, in order to know how to deal with it and avoid unnecessary abandonment of the shunt.

Connectomic Profiling Identifies Responders to Vagus Nerve Stimulation.

OBJECTIVE: Vagus nerve stimulation (VNS) is a common treatment for medically intractable epilepsy, but response rates are highly variable, with no preoperative means of identifying good candidates. This study aimed to predict VNS response using structural and functional connectomic profiling. METHODS: Fifty-six children, comprising discovery (n = 38) and validation (n = 18) cohorts, were recruited from 3 separate institutions. Diffusion tensor imaging was used to identify group differences in white matter microstructure, which in turn informed beamforming of resting-state magnetoencephalography recordings. The results were used to generate a support vector machine learning classifier, which was independently validated. This algorithm was compared to a second classifier generated using 31 clinical covariates. RESULTS: Treatment responders demonstrated greater fractional anisotropy in left thalamocortical, limbic, and association fibers, as well as greater connectivity in a functional network encompassing left thalamic, insular, and temporal nodes (p < 0.05). The resulting classifier demonstrated 89.5% accuracy and area under the receiver operating characteristic (ROC) curve of 0.93 on 10-fold cross-validation. In the external validation cohort, this model demonstrated an accuracy of 83.3%, with a sensitivity of 85.7% and specificity of 75.0%. This was significantly superior to predictions using clinical covariates alone, which exhibited an area under the ROC curve of 0.57 (p < 0.008). INTERPRETATION: This study provides the first multi-institutional, multimodal connectomic prediction algorithm for VNS, and provides new insights into its mechanism of action. Reliable identification of VNS responders is critical to mitigate surgical risks for children who may not benefit, and to ensure cost-effective allocation of health care resources. ANN NEUROL 2019;86:743-753.

Paediatric spondylodiscitis: a 10-year single institution experience in management and clinical outcomes.

PURPOSE: Discitis in the paediatric population poses diagnostic challenges due to non-specific presenting symptoms and difficulty with expressing pain in non-communicating children. Discitis remains a relatively rare condition in the paediatric population and previous reports are limited to small cohorts. In this article, we report our experience in management of discitis over a 10-year period and review the literature on this topic. METHODS: We retrospectively reviewed cases of paediatric discitis/spondylodiscitis over a 10-year period between 2008 and 2018 managed in our regional paediatric neurosurgery unit. Relevant demographic information, microbiological data, blood investigation profile, antibiotic treatment duration and clinical outcomes were interrogated from clinical notes and electronic databases and further analysed. RESULTS: Overall, 21 cases of paediatric discitis were identified from year 2008 to 2018 with a female to male ratio of 1.3:1. The mean age at presentation was 4.3 years (range 1 to 15 years). Overall, there were 19 cases of lumbosacral/lumbar, 1 thoracic and 1 cervical discitis. The mean duration of follow-up was 20 months (range 6 to 69 months). The most common presenting features were back pain and refusal to walk/sit or weight bear. Erythrocyte sedimentation rate (ESR) was found to be more sensitive than C-reactive protein (CRP) (sensitivity 78% versus 38%) in our cohort. Computer tomography (CT)-guided biopsy was performed in five cases and only one of these was positive (20%). All patients were treated with intravenous antibiotics with resolution of discitis. CONCLUSIONS: Presentation of discitis in children can be non-specific and requires high index of suspicion. CT-guided biopsy in our cohort revealed a low rate of positive cultures. Despite negative blood cultures and CT-guided biopsy results, empirical intravenous antibiotics were effective in treating discitis successfully. In our cohort, low yield of CT-guided biopsy does not support its use on each case and this may be reserved for cases resistant to antimicrobial therapy or concerns regarding other pathology mimicking infection. Better understanding and awareness of this condition and its pathophysiology can lead to timely imaging, diagnosis and treatment.

Paediatric developmental venous anomalies (DVAs): how often do they bleed and where?

INTRODUCTION: Developmental venous anomalies (DVAs) are anomalies of venous drainage and considered a low-flow malformation. Studies evaluating natural history and risk factors for intracranial haemorrhage in the paediatric population are rare. We evaluate clinical and radiological features, risk factors and outcomes of paediatric DVAs. METHODS: A retrospective study was conducted over a 10-year period between 2004 and 2014. Medical records, imaging and prospective databases were reviewed. Three-hundred-and-three radiological studies in total were evaluated. RESULTS: Fifty-two children (20 boys and 32 girls [median age: 6 years] were identified with DVAs. Their age distribution was as follows: 1.9% neonates (< 1 month), 11.5% infants (1 month to 1 year), 30.8% 1-5 years, 30.8% 5-12 years and 25% 12-16 years. The majority (92.3%) presented with asymptomatic DVAs identified incidentally. Overall, anatomical distribution revealed predilection for frontal region (42.3%) with other common sites being posterior fossa (17.3%) and basal ganglia (13.5%). Temporal (11.5%), parietal (9.6%) and occipital (5.8%) were the remainder. Associated cavernous malformations (CMs) were present in 3/52 (5.8%), and no DVAs were associated with aneurysms or arteriovenous malformations (AVMs). Three patients had more than one DVA. There were three deaths unrelated to DVAs over median follow-up of 3.8 years. Four patients (7.7%) suffered DVA-related intracranial haemorrhage presenting with neurological deficits. The ages of the children with DVA-related haemorrhages were 21 days, 2 years and 6 months, 7 years and 1 month and 11 years and 7 months. Left-sided DVA haemorrhages predominated (3/4, 75%). The relative risk of a cerebellar DVA haemorrhage compared to its supratentorial counterpart was 5.35 (OR 6.8, 95% CI 0.8-58). DISCUSSION: DVA-related haemorrhage is sevenfold greater in our paediatric cohort compared to adults and is significantly associated with cerebellar location and cavernous malformations. There were no haemorrhages over a median period of 3.8 years of prospective follow-up.

The 'transverse guard' wound dressing technique to reduce faecal contamination after spinal surgery in neonates and infants.

Wound care following lower spinal surgery in infants, especially open lumbosacral myelomeningocele (MMC) repair is challenging for a number of reasons: the babies' small size, uneven contour of the natal cleft, proximity of the wound to the perianal area, continuous soiling by loose/poorly-formed stool, and fragile skin. Faecal contamination of the wound can lead to infection, ascending meningitis and further morbidity. A single adhesive dressing does not reliably obliterate the space in the natal cleft and, therefore, does not prevent faecal material tracking rostrally underneath the dressing. This increases the risk of contamination and necessitates frequent wound dressing changes. The authors describe the use of the 'transverse guard', a simple technique routinely used in their unit that help overcome these problems. They also report on the wound infection rates of neonates undergoing open MMC repair who had the new dressings versus those who had conventional dressings.

Beyond the panel: preconception screening in consanguineous couples using the TruSight One "clinical exome".

PURPOSE: To provide proof of concept by broadening preconception screening beyond targeted testing to inform reproductive risk in consanguineous couples. METHODS: Consanguineous couples were screened for autosomal recessive and X-linked disorders using the TruSight One panel of 4,813 genes associated with human disease. RESULTS: We recruited 22 couples, of whom 15 elected to have sequencing. We found four couples to be at risk of autosomal recessive disorders, including one with a child affected by Poretti-Boltshauser syndrome (a diagnosis not made prior to the study) and another previously known to carry a ß-globin variant. Two couples were found to carry variants unrelated to known family history. These variants were in the genes C5orf42 (associated with Joubert syndrome and orofaciodigital syndrome) and GYS2 (associated with glycogen synthase deficiency). One known variant was not detected-a single exon deletion in FAM20C. We would not expect to identify this variant with the methodology employed. Of the four variants identified, only the ß-globin variant would have been found using available commercial preconception screening panels. CONCLUSION: Preconception screening of consanguineous couples for recessive and X-linked disorders using genomic sequencing is practicable, and is likely to detect many more at-risk couples than any targeted panel could achieve. A couples-based approach greatly reduces the associated analysis and counselling burden.

Predicting first-episode psychosis patients who will never relapse over 10 years.

BACKGROUND: Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode. METHOD: Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning. RESULTS: Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders. CONCLUSIONS: Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP.

Consent in paediatric neurosurgery: adequacy of documentation and parental perspectives.

INTRODUCTION: Consenting paediatric patients for surgical procedures remains inherently unique in that it is underpinned by principles such as parental responsibility, assessment of the child's capacity to consent, and adherence to national/legal guidelines. Quality record keeping is an important objective evidence to demonstrate the highest standards of medical care provided to our patients. The consent form is a crucial medical record encapsulating the attainment of informed consent from a parent/guardian for performing a procedure on their child. We aimed to prospectively evaluate the consenting process in our department to assess adequacy of documentation and parental perspectives. METHODS: A prospective study using qualitative descriptive design was conducted with parents of 50 children requiring neurosurgical procedures over a 3-month period. RESULTS: All patients understood the primary diagnosis and type of surgery. Procedure-specific risks were understood by 98% and 84% could remember the mentioning of general risks of surgery. Only a minority of parents (24%) could recollect that alternative options of management including no treatment were discussed. In cases where relevant, laterality was only documented in 56% of consent forms. All patients felt that an informed decision regarding consent to surgery was made. However, 12% suggested areas where further improvement could be made in the timing of consent and the way information could be better provided. DISCUSSION: Consent is more than a signature on a form. It provides objective evidence of a shared decision-making process between the surgeon, patient, and their parent/guardian. Our initial study highlights multiple areas for improvement.

Craniofacial Approaches to Pediatric Orbital Tumors.

Primary pediatric orbital tumors requiring surgery are uncommon and often require multidisciplinary management. Commonly used surgical approaches to the orbit include transconjunctival, transcutaneous (eyelid), transcranial, or extracranial osteotomies. This paper reviews a 10-year experience of cases that required a transcranial or extracranial surgical approach at the Birmingham Children's Hospital. A total of 9 patients were identified between the years 2008 to 2017. Pathologies included rhabdomyosarcoma, juvenile ossifying fibroma, optic nerve glioma, and retinoblastoma. Surgical approaches to the orbit included supraorbital bar osteotomy (transcranial) or lateral orbitotomy (extracranial). Surgical team members included neurosurgery, craniofacial surgery, and ophthalmology. This study aims to review the role of surgery in management as well as the specific indications for performing transcranial or extracranial osteotomies. It also highlights the excellent access achieved with the use of these osteotomies in certain cases, especially when compared with transconjunctival or transcutaneous approaches.

A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations.

PURPOSE: The craniosynostoses are characterized by premature fusion of one or more cranial sutures. The relative contribution of previously reported genes to craniosynostosis in large cohorts is unclear. Here we report on the use of a massively parallel sequencing panel in individuals with craniosynostosis without a prior molecular diagnosis. METHODS: A 20-gene panel was designed based on the genes' association with craniosynostosis, and clinically validated through retrospective testing of an Australian and New Zealand cohort of 233 individuals with craniosynostosis in whom previous testing had not identified a causative variant within FGFR1-3 hot-spot regions or the TWIST1 gene. An additional 76 individuals were tested prospectively. RESULTS: Pathogenic or likely pathogenic variants in non-FGFR genes were identified in 43 individuals, with diagnostic yields of 14% and 15% in retrospective and prospective cohorts, respectively. Variants were identified most frequently in TCF12 (N = 22) and EFNB1 (N = 8), typically in individuals with nonsyndromic coronal craniosynostosis or TWIST1-negative clinically suspected Saethre-Chotzen syndrome. Clinically significant variants were also identified in ALX4, EFNA4, ERF, and FGF10. CONCLUSION: These findings support the clinical utility of a massively parallel sequencing panel for craniosynostosis. TCF12 and EFNB1 should be included in genetic testing for nonsyndromic coronal craniosynostosis or clinically suspected Saethre-Chotzen syndrome.

Consent: an event or a memory in lumbar spinal surgery? A multi-centre, multi-specialty prospective study of documentation and patient recall of consent content.

STUDY DESIGN: Prospective, multi-centre, multi-specialty medical notes review and patient interview. PURPOSE: The consenting process is an important communication tool which also carries medico-legal implications. While written consent is a pre-requisite before spinal surgery in the UK, the standard and effectiveness of the process have not been assessed previously. This study assesses standard of written consent for elective lumbar decompressive surgery for degenerative disc disease across different regions and specialties in the UK; level of patient recall of the consent content; and identifies factors which affect patient recall. METHODS: Consent forms of 153 in-patients from 4 centres a, b, c, d were reviewed. Written documentation of intended benefits, alternative treatments and operative risks was assessed. Of them, 108 patients were interviewed within 24 h before or after surgeries to assess recall. RESULTS: The written documentation rates of the operative risks showed significant inter-centre variations in haemorrhage and sphincter disturbance (P = 0.000), but not for others. Analysis of pooled data showed variations in written documentation of risks (P < 0.0005), highest in infection (96.1%) and lowest in recurrence (52.3%). For patient recall of these risks, there was no inter-centre variation. Patients' recall of paralysis as a risk was highest (50.9%) and that of recurrence was lowest (6.5%). Patients <65 years old recalled risks better than those ≥65, significantly so for infection (29.9 vs 9.7%, P = 0.027). Patients consented >14 days compared to <2 days before their surgeries had higher recall for paralysis (65.2 vs 43.7%) and recurrence (17.4 vs 2.8%). Patient recall was independent of consenter grade. CONCLUSION: Overall, the standard of written consent for elective lumbar spinal decompressive surgery was sub-optimal, which was partly reflected in the poor patient recall. While consenter seniority did not affect patient recall, younger age and longer consent-to-surgery time improved it.