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This review updates the radiologist on current epilepsy surgery practice in children, with a specific focus on the role of imaging in pre-surgical work-up, current and novel surgical techniques, expected post-surgical imaging appearances and important post-operative complications. A comprehensive review of the current and emerging international practices in paediatric epilepsy surgical planning and post-operative imaging is provided with details on case-based radiological findings. A detailed discussion of the pathophysiology and imaging features of different epileptogenic lesions will not be discussed as this is not the objective of this paper. Epilepsy surgery can be an effective method to control seizures in certain children with drug-resistant focal epilepsy. Early surgery in selected appropriate cases can lead to improved cognitive and developmental outcome. Advances in neurosurgical techniques, imaging and neuroanaesthesia have driven a parallel expansion in the array of epilepsy conditions which are potentially treatable with surgery. The range of surgical options is now wide, including minimally invasive ablative procedures for small lesions such as hypothalamic hamartomata, resections for focal lesions like hippocampal sclerosis and complex disconnective surgeries for multilobar conditions like Sturge Weber Syndrome and diffuse cortical malformations. An awareness of the surgical thinking when planning epilepsy surgery in children, and the practical knowledge of the operative steps involved will promote more accurate radiology reporting of the post-operative scan.

Purpose Failure to recognise involvement of the insula / opercula (I/O) region is associated with poor outcome in epilepsy surgery. Recognition is challenging due to high connectivity with adjacent structures resulting in variable and misleading semiology, often subjective and therefore likely to be underreported by children. In this study we explored prevalence and characteristics of I/O involvement in paediatric patients undergoing sEEG exploration. Method We retrospectively included all consecutive patients undergoing sEEG at our centre between 11/2014 and 01/2018 with at least three contacts within I/O and excluded those with undetermined seizure onset zone (SOZ) by sEEG. We divided patients into three groups: 1) SOZ in I/O, 2) spread to I/O and 3) no I/O involvement. We compared pre-invasive characteristics, sEEG results, surgery and outcome for each group. Results 29 of all 53 consecutive patients had an identified SOZ by sEEG and at least three contacts within the I/O and were included. 41% had I/O SOZ, 38% had I/O spread and 21% had no I/O involvement. Insula associated symptoms described in adult literature were not statistically different between the three groups. Complications due to sEEG were low (2 of 53 patients). Following I/O surgery, 63% were seizure free while an additional 26% of patients achieved seizure reduction. Postoperative deficits were seen in 75% of the patients but completely resolved in all but one patient. Conclusions Our data suggest an important role of the I/O region with frequent onset or propagation to the I/O region (at least 64% of all 53 sEEG cases). Semiology appears less specific than in adults. Insula depth electrode insertion is safe with subsequent good surgical outcomes albeit common transient deficits.

All children, young people, and indeed adults with a recent onset suspected seizure should be seen promptly by a physician with expertise in epilepsy, to avoid misdiagnosis as well as to ensure precise and early diagnosis, and to recognize serious non-neurological diagnoses, especially cardiological ones. Paediatric epilepsy offers particular challenges in terms of diagnosis, evaluation, and management. Surgical treatment is a safe and effective management strategy in selected patients. In order to optimize seizure and cognitive outcome, surgery should be offered at an early stage in suitable, drug-resistant cases. This chapter summarizes the key steps in diagnosis, presurgical evaluation, and operative techniques required to treat this patient group and highlights the special considerations required in the paediatric population.

The presence of interictal epileptiform discharges on electroencephalography (EEG) may indicate increased epileptic seizure risk and on invasive EEG are the signature of the irritative zone. In highly epileptogenic lesions – such as cortical tubers in tuberous sclerosis – these discharges can be recorded with intracranial stereotactic EEG as part of the evaluation for epilepsy surgery. Yet the network mechanisms that underwrite the generation and spread of these discharges remain poorly understood, limiting their current diagnostic use.Here, we investigate the dynamics of interictal epileptiform discharges using a combination of quantitative analysis of invasive EEG recordings and mesoscale neural mass modelling of cortical dynamics. We first characterise spatially organised local dynamics of discharges recorded from 36 separate tubers in 8 patients with tuberous sclerosis. We characterise these dynamics with a set of competing explanatory network models using dynamic causal modelling. Bayesian model comparison of plausible network architectures suggests that the recurrent coupling between neuronal populations within – and adjacent to – the tuber core explains the travelling wave dynamics observed in these patient recordings.Our results – based on interictal activity – unify competing theories about the pathological organisation of epileptic foci and surrounding cortex in patients with tuberous sclerosis. Coupled oscillator dynamics have previously been used to describe ictal activity, where fast travelling ictal discharges are commonly observed within the recruited seizure network. The interictal data analysed here add the insight that this functional architecture is already established in the interictal state. This links observations of interictal EEG abnormalities directly to pathological network coupling in epilepsy, with possible implications for epilepsy surgery approaches in tuberous sclerosis.Significance StatementInterictal epileptiform discharges (IEDs) are clinically important markers of an epileptic brain. Here we link local IED spread to network coupling through a combination of clinical recordings in paediatric patients with tuberous sclerosis complex, quantitative EEG analysis of interictal discharges spread, and Bayesian inference on coupled neural mass model parameters. We show that the kinds of interictal discharges seen in our patients require recurrent local network coupling extending beyond the putative seizure focus and that in fact only those recurrent coupled networks can support seizure-like and interictal dynamics when run in simulation. Our findings provide a novel integrated perspective on emergent epileptic dynamics in human patients.

Background: The incidence of non-traumatic intracranial haemorrhage among neonates is less than among adults. However, the outcomes are generally poor, with high rates of morbidity and mortality. Non-traumatic intracranial haemorrhage can cause a sudden increase in intracranial pressure, requiring emergency craniotomy for evacuation. Methods: We report 4 cases following craniotomy for non-traumatic acute intracranial haematoma in very young children. The surgical technique and postoperative course are discussed, with emphasis on dural repair to avoid resistant pseudomeningocele. Results: Despite successful management of the acutely raised intracranial pressure, all patients afterwards developed tense pseudomeningoceles and required formal dural repair. This led to a change in institutional practice and modifications to the surgical technique. Conclusion: The authors highlight the postoperative occurrence of resistant pseudomeningoceles in young children after clot evacuations and leaving the dura open. They describe the surgical procedures to avoid these pseudomeningoceles.

INTRODUCTION: Stereotactic brain biopsy represents one of the earliest applications of surgical robotics. The aim of the present systematic review and bibliometric analysis was to evaluate the literature supporting robot-assisted brain biopsy and the extent to which the scientific community has accepted the technique. METHODS: The Cochrane and PubMed databases were searched over a 30-year period between 1st of January 1988 and 31st of December 2017. Titles and abstracts were screened to identify publications that met the following criteria: (1) featured patients with brain pathology, (2) undergoing stereotactic brain biopsy, (3) reporting robot-assisted surgery, and (4) outcome data were provided. The reference lists of selected studies were also sought, and expert opinion sought to identify further eligible publications. Selected manuscripts were then reviewed, and data extracted on effectiveness and safety. The status of scientific community acceptance was determined using a progressive scholarly acceptance analysis. RESULTS: All identified studies were non-randomised, including 1 retrospective cohort study and 14 case series or reports. The diagnostic biopsy rate varied from 75 to 100%, and the average target accuracy varied from 0.9 to 4.5 mm. Use of the robot was aborted in two operations owing to geometric inaccessibility and an error in image registration but no associated adverse events were reported. A compounding progressive scholarly acceptance analysis suggested a trend towards acceptance of the technique by the scientific community. CONCLUSIONS: In conclusion, robot-assisted stereotactic brain biopsy is an increasingly mainstream tool in the neurosurgical armamentarium. Further evaluation should proceed along the IDEAL framework with research databases and comparative trials.

ObjectiveResective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart.MethodsSixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor.ResultsOver time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02–1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%–5.3%, p = 0.7).ConclusionImprovements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.

OBJECT A dermal sinus tract is a common form of occult spinal dysraphism. The presumed etiology relates to a focal failure of disjunction resulting in a persistent adhesion between the neural and cutaneous ectoderm. Clinical and radiological features can appear innocuous, leading to delayed diagnosis and failure to appreciate the implications or extent of the abnormality. If it is left untreated, complications can include meningitis, spinal abscess, and inclusion cyst formation. The authors present their experience in 74 pediatric cases of spinal dermal tract in an attempt to identify which clinical and radiological factors are associated with an infective presentation and to assess the reliability of MRI in evaluating this entity. METHODS Consecutive cases of spinal dermal tract treated with resection between 1998 and 2010 were identified from the departmental surgical database. Demographics, clinical history, and radiological and operative findings were collected from the patient records. The presence or absence of active infection (abscess, meningitis) at the time of neurosurgical presentation and any history of local sinus discharge or infection was assessed. Magnetic resonance images were reviewed to evaluate the extent of the sinus tract and determine the presence of an inclusion cyst. Radiological and operative findings were compared. RESULTS The surgical course was uncomplicated in 90% of 74 cases eligible for analysis. Magnetic resonance imaging underreported the presence of both an intradural tract (MRI 46%, operative finding 86%) and an intraspinal inclusion cyst (MRI 15%, operative finding 24%). A history of sinus discharge (OR 12.8, p = 0.0003) and the intraoperative identification of intraspinal inclusion cysts (OR 5.6, p = 0.023) were associated with an infective presentation. There was no significant association between the presence of an intradural tract discovered at surgery and an infective presentation. CONCLUSIONS Surgery for the treatment of spinal dermal tract carries a low morbidity. While it seems intuitive that tracts without intradural extension carry a low risk of spinal cord tethering, it is not possible to reliably detect these cases using MRI. Similarly, intraspinal dermoid cannot be reliably excluded using MRI and carries an increased risk of infection. These points justify excision together with intradural exploration of all spinal dermal sinus tracts.

Objective Glioneuronal tumors (GNTs) are well-recognized causes of chronic drug-resistant focal epilepsy in children. Our practice involves an initial period of radiological surveillance and antiepileptic medications, with surgery being reserved for those with radiological progression or refractory seizures. We planned to analyze the group of patients with low-grade GNTs, aiming to identify factors affecting seizure and cognitive outcomes. Methods We retrospectively reviewed the medical records of 150 children presenting to Great Ormond Street Hospital with seizures secondary to GNTs. Analysis of clinical, neuroimaging, neuropsychological, and surgical factors was performed to determine predictors of outcome. Seizure outcome at final follow-up was classified as either seizure-free (group A) or not seizure-free (group B) for patients with at least 12-months follow-up postsurgery. Full-scale intelligence quotient (FSIQ) was used as a measure of cognitive outcome. Results Eighty-six males and 64 females were identified. Median presurgical FSIQ was 81. One hundred twenty-one patients (80.5%) underwent surgery. Median follow-up after surgery was 2 years, with 92 patients (76%) having at least 12 months of follow-up after surgery. Seventy-four patients (80%) were seizure-free, and 18 (20%) continued to have seizures. Radiologically demonstrated complete tumor resection was associated with higher rates of seizure freedom (P = .026). Higher presurgical FSIQ was related to shorter epilepsy duration until surgery (P = .012) and to older age at seizure onset (P = .043). Significance A high proportion of children who present with epilepsy and GNTs go on to have surgical tumor resection with excellent postoperative seizure control. Complete resection is associated with a higher chance of seizure freedom. Higher presurgical cognitive functioning is associated with shorter duration of epilepsy prior to surgery and with older age at seizure onset. Given the high rate of eventual surgery, early surgical intervention should be considered in children with continuing seizures associated with GNTs.

Background Hypothalamic hamartomas are rare brain malformations characterised by a syndrome of seizures, central precocious puberty, behavioural, emotional and cognitive difficulties. Behavioural and emotional symptoms often present the greatest burden of morbidity for patients and families. Due to the rarity of the disease, the heterogeneity of the presentation, and the multifactorial aetiology, prognosis is varied and management strategies are yet to be standardised. Methods The notes of 46 paediatric cases with hypothalamic hamartomas were examined retrospectively. Demographics, behavioural and emotional symptoms, cognitive functioning, epileptic profiles, and pubertal status were recorded. ICD-10 codes for psychiatric disorder were assigned to applicable cases. Results 61% of cases were male. The mean age at diagnosis was 4.2 years (0–14 years). 71.7% of the cases met criteria for ≥1 ICD-10 Axis 1 diagnosis (psychiatric disorder). ADHD, Generalised Anxiety Disorder and ASD were most frequent. 46% experienced characteristic rage attacks. 50% had some degree of intellectual disability, most commonly mild. 63% of cases experienced seizures. 40% had precocious puberty. Conclusion This dataset represents one of the largest in the paediatric hypothalamic hamartoma literature. A significant proportion demonstrate psychiatric disorders and intellectual disability. Aetiology relates to a range of interacting biological and psychosocial factors. The major biological components are direct brain-behaviour effects from disrupted hypothalamic functioning and frequent seizures, alongside influence from antiepileptic medications. Psychosocial factors are those common to all chronic neurological conditions including low self-esteem, disrupted schooling and impact from family/social functioning. Currently, there are limited non-surgical evidence-based treatments for these complex cases. Defining the clinical presentation for a disease is a prerequisite to developing effective treatments. This data contributes to international efforts with this aim in mind.

Surgery for epilepsy dates back to 1886 and has undergone significant developments. Today it is considered a key treatment modality in patients who are resistant to pharmacological intervention. It improves seizure control, cognition and quality of life. New technologies, advances in surgical technique and progress in scientific research underlie the expansion of surgery in epilepsy treatment. Effectiveness of surgical treatment depends on several factors including the type of epilepsy, the underlying pathology and the localisation of the epileptogenic zone. Timely referral to an experienced epilepsy surgery centre is important to allow the greatest chance of seizure control and to minimise associated morbidity and mortality. Following referral, patients undergo thorough presurgical investigation to evaluate their suitability for surgery. The commonest form of epilepsy treated by surgery is mesial temporal lobe sclerosis and there is Class I evidence for the medium-term efficacy of temporal lobe resection from two randomised control trials. Various other forms of epilepsy are now considered for resective and neuromodulatory surgical intervention due to favourable results. In this article, the authors review the current status of surgical treatment for epilepsy including the presurgical evaluation of patients, surgical techniques and the future directions in epilepsy surgery.

Aim To describe 20 years of experience with corpus callosotomy at Great Ormond Street Hospital for Children, London and the Children's Hospital at Westmead, Sydney. Method Records of patients who underwent corpus callosotomy between January 1995 and December 2015 were reviewed. Complications of surgery and changes in seizure type and frequency, injuries, and use of antiepileptic drugs were recorded. Drop attacks were analysed using Kaplan–Meier event-free survival curves. Multivariable regression analysis was used to assess the effect of clinical characteristics on outcome at last follow-up. Results Inclusion criteria were met for 55 patients younger than 18 years of age. Median follow-up length was 36 months. At the last follow-up, 26 out of 55 patients (47%) had rare or no drop attacks. In those without a good outcome at final follow-up, 26 out of 29 (90%) had drop attacks return within 12 months of surgery. There were no preoperative predictors of developing drop attacks postoperatively. The median number of antiepileptic drugs significantly reduced from three to two. Transient neurological complications were experienced by 11 out of 55 patients (20%) and 6 out of 55 patients had surgical complications (11%). Interpretation Corpus callosotomy is a well-tolerated procedure that is effective at reducing the severity of drop attacks in paediatric patients. Drop attacks that do return are likely to do so within 12 months and the number of antiepileptic drugs can be significantly reduced. What this paper adds Corpus callosotomy is an effective palliative treatment and well tolerated in children. Good outcomes for the first 12 months after surgery were likely to continue. The number of antiepileptic drugs can be significantly reduced after corpus callosotomy. Patients with fewer than three types of seizure had better outcomes. There were fewer injuries from drop attacks after surgery.

Glioneuronal tumours are an important cause of treatment-resistant epilepsy. Subtypes of tumour are often poorly discriminated by histological features and may be difficult to diagnose due to a lack of robust diagnostic tools. This is illustrated by marked variability in the reported frequencies across different epilepsy surgical series. To address this, we used DNA methylation arrays and RNA sequencing to assay the methylation and expression profiles within a large cohort of glioneuronal tumours. By adopting a class discovery approach, we were able to identify two distinct groups of glioneuronal tumour, which only partially corresponded to the existing histological classification. Furthermore, by additional molecular analyses, we were able to identify pathogenic mutations in BRAF and FGFR1, specific to each group, in a high proportion of cases. Finally, by interrogating our expression data, we were able to show that each molecular group possessed expression phenotypes suggesting different cellular differentiation: astrocytic in one group and oligodendroglial in the second. Informed by this, we were able to identify CCND1, CSPG4, and PDGFRA as immunohistochemical targets which could distinguish between molecular groups. Our data suggest that the current histological classification of glioneuronal tumours does not adequately represent their underlying biology. Instead, we show that there are two molecular groups within glioneuronal tumours. The first of these displays astrocytic differentiation and is driven by BRAF mutations, while the second displays oligodendroglial differentiation and is driven by FGFR1 mutations. Electronic supplementary material The online version of this article (doi:10.1007/s00401-017-1773-z) contains supplementary material, which is available to authorized users.

Background In the evaluation of Stereo-Electroencephalography (SEEG) signals, the physicist’s workflow involves several operations, including determining the position of individual electrode contacts in terms of both relationship to grey or white matter and location in specific brain regions. These operations are (i) generally carried out manually by experts with limited computer support, (ii) hugely time consuming, and (iii) often inaccurate, incomplete, and prone to errors. Results In this paper we present SEEG Assistant, a set of tools integrated in a single 3DSlicer extension, which aims to assist neurosurgeons in the analysis of post-implant structural data and hence aid the neurophysiologist in the interpretation of SEEG data. SEEG Assistant consists of (i) a module to localize the electrode contact positions using imaging data from a thresholded post-implant CT, (ii) a module to determine the most probable cerebral location of the recorded activity, and (iii) a module to compute the Grey Matter Proximity Index, i.e. the distance of each contact from the cerebral cortex, in order to discriminate between white and grey matter location of contacts. Finally, exploiting 3DSlicer capabilities, SEEG Assistant offers a Graphical User Interface that simplifies the interaction between the user and the tools. SEEG Assistant has been tested on 40 patients segmenting 555 electrodes, and it has been used to identify the neuroanatomical loci and to compute the distance to the nearest cerebral cortex for 9626 contacts. We also performed manual segmentation and compared the results between the proposed tool and gold-standard clinical practice. As a result, the use of SEEG Assistant decreases the post implant processing time by more than 2 orders of magnitude, improves the quality of results and decreases, if not eliminates, errors in post implant processing. Conclusions The SEEG Assistant Framework for the first time supports physicists by providing a set of open-source tools for post-implant processing of SEEG data. Furthermore, SEEG Assistant has been integrated into 3D Slicer, a software platform for the analysis and visualization of medical images, overcoming limitations of command-line tools.

The relationship between cerebral blood volume (CBV) and flow (CBF) has been widely studied. One of the most significant early studies was by Grubb et al (1974 Stroke 5 630-9), who conducted hypercapnia studies in primates with positron emission tomography (PET) and empirically found CBV = 0.8 CBF(0.38). The exponent used here has since been known as the Grubb's exponent. In this paper, we define a similar exponent known as the modified Grubb's exponent, G', which is based on CBV and cerebral blood flow velocity (CBFV) estimated by near infrared spectroscopy (NIRS) and transcranial Doppler respectively, i.e. G' = log(CBV/CBV(0))/log(CBFV/CBFV(0)), where CBV(0) and CBFV(0) are baseline values. The aim of this study was to estimate the nominal value of the modified Grubb's exponent in healthy human brains. We conducted hypercapnia and hypocapnia studies on 14 healthy adult subjects. The correlation coefficient between log(CBV/CBV(0)) and log(CBFV/CBFV(0)) is 0.71 (p < 0.0001). We found a modified Grubb's exponent of 0.13 (the 95% confidence bounds are 0.10 and 0.17) which is expectedly lower than the conventional Grubb's exponents estimated by other techniques. The modified Grubb's exponent is a simple measure to quantify the hemodynamics between local CBV and global CBFV in the brain and as such may provide insight on brain physiology. Both NIRS and transcranial Doppler techniques are non-invasive and portable, facilitating future studies in other population groups such as brain-injured patients.

SummaryObjective Corpus callosotomy is a palliative neurosurgical treatment for patients with either generalized or multifocal refractory epilepsy and injurious drop attacks. This report aims to systematically review the pediatric literature. Methods Medline, Embase, Web of Knowledge, and Scopus were searched systematically for published articles on treatment outcomes of corpus callosotomy for refractory epilepsy. Studies were included if the patient population was younger than 18 at the time of surgery and median follow-up was >1 year. Studies were excluded if resective surgery was also performed. Results A total of 12 articles met inclusion criteria. All articles were retrospective case series, with the exception of one being a prospectively designed retrospective case series. There was very little agreement among authors on the definition of a good seizure outcome. Articles that used the Engel classification found that 88.2% of total corpus callosotomy patients had a worthwhile reduction in seizures compared with 58.6% of patients who underwent anterior corpus callosotomy (p

Traumatic brain injury causes diffuse axonal injury and loss of cortical neurons. These features are well recognized histologically, but their in vivo monitoring remains challenging. In vivo cortical microdialysis samples the extracellular fluid adjacent to neurons and axons. Here, we describe a novel neuronal proteolytic pathway and demonstrate the exclusive neuro-axonal expression of Pavlov's enterokinase. Enterokinase is membrane bound and cleaves the neurofilament heavy chain at positions 476 and 986. Using a 100 kDa microdialysis cut-off membrane the two proteolytic breakdown products, extracellular fluid neurofilament heavy chains NfH(476-986) and NfH(476-1026), can be quantified with a relative recovery of 20%. In a prospective clinical in vivo study, we included 10 patients with traumatic brain injury with a median Glasgow Coma Score of 9, providing 640 cortical extracellular fluid samples for longitudinal data analysis. Following high-velocity impact traumatic brain injury, microdialysate extracellular fluid neurofilament heavy chain levels were significantly higher (6.18 +/- 2.94 ng/ml) and detectable for longer (> 4 days) compared with traumatic brain injury secondary to falls (0.84 +/- 1.77 ng/ml, < 2 days). During the initial 16 h following traumatic brain injury, strong correlations were found between extracellular fluid neurofilament heavy chain levels and physiological parameters (systemic blood pressure, anaerobic cerebral metabolism, excessive brain tissue oxygenation, elevated brain temperature). Finally, extracellular fluid neurofilament heavy chain levels were of prognostic value, predicting mortality with an odds ratio of 7.68 (confidence interval 2.15-27.46, P = 0.001). In conclusion, this study describes the discovery of Pavlov's enterokinase in the human brain, a novel neuronal proteolytic pathway that gives rise to specific protein biomarkers (NfH(476-986) and Nf(H476-1026)) applicable to in vivo monitoring of diffuse axonal injury and neuronal loss in traumatic brain injury.

Introduction Cerebral microdialysis is an established research tool that is used by an increasing number of neurocritical care units as a component of bedside multimodality monitoring. Body fluid biomarkers are an emerging tool for the assessment of brain injury. The correct interpretation of body fluid biomarker levels depends on the degree of recovery, i.e. relative recovery and the accuracy of the analytical technique. Methods In vitro recovery experiments were performed on 100 mL volumes of cerebrospinal fluid and solutions of S100B, glucose, lactate and pyruvate comparing relative recoveries using commercially available 20 kDa (CMA70) and 100 kDa (CMA71) microdialysis catheters. We also compared the CMA 600 microdialysis analyzer with a YSI 2003 STAT Plus™ analyzer for glucose and lactate to determine its reliability. Results Significantly, we demonstrate the improved recovery of the protein S100B using a larger molecular weight (MW) cut-off catheter (20 kDa range: 0.1–9%; 100 kDa range: 1.7–18.3%) while maintaining comparable performance for the conventional markers glucose, lactate and pyruvate. Additionally we found that the CMA 600 analyzer may be prone to overestimation of lactate readings at higher concentration with implications for clinical decision-making. Conclusion Our data demonstrates that the 100 kDa MW cut-off catheter allows for the improved recovery of macromolecules in cerebral microdialysis research while maintaining the value of existing MD data for routine clinical use.

Traumatic brain injury (TBI) remains a major cause of morbidity and mortality, particularly in young people. Despite encouraging animal studies, human trials assessing the use of pharmacological agents after TBI have all failed to show efficacy. Current management strategies are therefore directed towards providing an optimal physiological environment in order to minimize secondary insults and maximize the body's own regenerative processes. Modern neurocritical care management utilizes a host of monitoring techniques to identify or predict the occurrence of secondary insults and guide subsequent therapeutic interventions in an attempt to minimize the resulting secondary injury. Recent data suggest that the use of protocolized management strategies, informed by multimodality monitoring, can improve patient outcome after TBI. Developments in multimodality monitoring have allowed a movement away from rigid physiological target setting towards an individually tailored, patient-specific, approach. The wealth of monitoring information available provides a challenge in terms of data integration and accessibility and modern software applications may aid this process.

OBJECT The objective of this study was to evaluate the clinical utility of multitrajectory computer-assisted planning software (CAP) to plan stereoelectroencephalography (SEEG) electrode arrangements. METHODS A cohort of 18 patients underwent SEEG for evaluation of epilepsy at a single center between August 2013 and August 2014. Planning of electrodes was performed manually and stored using EpiNav software. CAP was developed as a planning tool in EpiNav. The user preselects a set of cerebral targets and optimized trajectory constraints, and then runs an automated search of potential scalp entry points and associated trajectories. Each trajectory is associated with metrics for a safety profile, derived from the minimal distance to vascular structures, and an efficacy profile, derived from the proportion of depth electrodes that are within or adjacent to gray matter. CAP was applied to the cerebral targets used in the cohort of 18 previous manually planned implantations to generate new multitrajectory implantation plans. A comparison was then undertaken for trajectory safety and efficacy. RESULTS CAP was applied to 166 electrode targets in 18 patients. There were significant improvements in both the safety profile and efficacy profile of trajectories generated by CAP compared with manual planning (p < 0.05). Three independent neurosurgeons assessed the feasibility of the trajectories generated by CAP, with 131 (78.9%) of 166 trajectories deemed suitable for implementation in clinical practice. CAP was performed in real time, with a median duration of 8 minutes for each patient, although this does not include the time taken for data preparation. CONCLUSIONS CAP is a promising tool to plan SEEG implantations. CAP provides feasible depth electrode arrangements, with quantitatively greater safety and efficacy profiles, and with a substantial reduction in duration of planning within the 3D multimodality framework.

Lumbosacral lipoma is a form of occult spinal dysraphism. It occurs in 1:4000 live births and can lead to neurological, urological and orthopaedic disturbance. Until recently, the perceived surgical wisdom has been that all lumbosacral lipomas should be treated with surgical debulking and spinal cord detethering in an attempt to prevent neurological deterioration. This philosophy is based on the assumptions that inevitable deterioration will occur without surgery, and that surgery is safe and effective. Over the last decade evidence has emerged to suggest that, in the absence of neurological or urological deterioration, conservative management may have a similar or even superior outcome when compared to traditional surgical techniques. Conversely data from a recent single institution experience suggest that radical lipoma removal may lead to better outcome. This chapter presents a management algorithm for newly diagnosed patients with spinal lipomas which aims to recognize the benign course of the disease in many asymptomatic patients and to provide effective long term treatment results for those who deteriorate.

We have previously used a continuous four-wavelength near-infrared spectrometer to measure changes in the cerebral concentrations of oxy-haemoglobin (Delta[HbO(2)] and deoxy-haemoglobin (Delta[HHb]) during head-up tilt in patients with primary autonomic failure. The measured changes in light attenuation also allow calculation of changes in the concentration of oxidized cytochrome-c-oxidase (Delta[(ox)CCO]), and this paper analyses the Delta[(ox)CCO] during the severe episodes of orthostatic hypotension produced by this experimental protocol. We studied 12 patients during a passive change in position from supine to a 60 degrees head-up tilt. The challenge caused a reduction in mean blood pressure of 59.93 (+/-26.12) mmHg (Mean (+/-SD), p < 0.0001), which was associated with a reduction in the total concentration of haemoglobin (Delta[HbT] = Delta[HbO(2)] + Delta[HHb]) of 5.02 (+/-3.81) microM (p < 0.0001) and a reduction in the haemoglobin difference concentration (Delta[Hb(diff)] = Delta[HbO(2)] - Delta[HHb]) of 14.4 (+/-6.73) microM (p < 0.0001). We observed a wide range of responses in Delta[(ox)CCO]. Six patients demonstrated a drop in Delta[(ox)CCO] (0.17 +/- 0.15 microM); four patients demonstrated no change (0.01 +/- 0.12 microM) and two patients showed an increase in Delta[(ox)CCO] (0.21 +/- 0.01 microM). Investigation of the association between the changes in concentrations of haemoglobin species and the Delta[(ox)CCO] for each patient show a range of relationships. This suggests that a simple mechanism for crosstalk, which might produce artefactual changes in [(ox)CCO], is not present between the haemoglobin and the (ox)CCO NIRS signals. Further investigation is required to determine the clinical significance of the changes in [(ox)CCO].

Cerebral microdialysis is a well-established laboratory tool that is increasingly used as a bedside monitor to provide on-line analysis of brain tissue biochemistry during neurointensive care. This review describes the principles of cerebral microdialysis and the rationale for its use in the clinical setting, including discussion of the most commonly used microdialysis biomarkers of acute brain injury. Potential clinical applications are reviewed and future research applications identified. Microdialysis has the potential to become an established part of mainstream multi-modality monitoring during the management of acute brain injury but at present should be considered a research tool for use in specialist centres.

This article investigates the relationship between brain extracellular fluid free phenytoin concentration and plasma free phenytoin concentration in adults with acute brain injury. Daily cerebral microdialysate free phenytoin concentration was measured in eight adults with acute brain injury and compared with simultaneous measurement of plasma free phenytoin concentration. The group data revealed no significant correlation between microdialysate and plasma free phenytoin concentration (r = 0.34, p = 0.41). However, in two patients, with a sufficient number of samples for intra-individual analysis, there was a significant correlation between microdialysate and plasma free phenytoin concentration ( r = 0.92, p

Recent advances in digital imaging have made Faxitron microradiography an attractive alternative to intra-operative conventional specimen radiography (CSR) for the excision of wirelocalized breast lesions. Faxitron specimen analysis time, usefulness of digital image manipulation and re-excision rates were evaluated in comparison to CSR in 299 consecutive wire-localized excisions for mammographically suspicious non-palpable breast lesions (172 procedures with Faxitron, 127 with CSR) in a non-randomized study. The corresponding mean operation times were 34.7 vs. 42.7 min and the respective re-excision rates were 19.8% vs. 31.5% (no significant difference on chi analysis P < 0.1). Faxitron digital image manipulation led to cavity biopsies in 50% (60/121) of the cancer excisions. In 19 of these (16%), histological excision margins were converted from incomplete to complete. The shorter Faxitron mean operating time enables an additional wire-localized operation per theatre list. Digital imaging guides the surgeon for additional cavity biopsies, resulting in re-excision rates as good as CSR.

We describe the first case in the literature of complication-free epilepsy surgery in a paediatric patient with collagen type IV alpha 1 (COL4A1) mutation. This is a case report. COL4A1 mutations disrupt the integrity of vascular basement membranes, so predisposing to a broad spectrum of disorders including periventricular leucomalacia, haemorrhagic stroke, aneurysm formation, epilepsy and developmental delay. Intracranial haemorrhage is reported and may be recurrent or associated with trauma and anticoagulant therapy. Children have an increased risk of stroke with general anaesthesia. A 6-year-old girl, COL4A1 mutation positive, had drug-resistant epilepsy, cerebral palsy and developmental delay. Following presurgical evaluation, she was a candidate for corpus callosotomy. Previous general anaesthesia had been uncomplicated. Preoperative full blood count and coagulation studies were normal. Perioperatively, normotension was maintained, and anticoagulation was avoided. A complete corpus callosotomy was performed with no intracranial haemorrhage or other perioperative complications. Although there is an increased risk of intracranial haemorrhages in COL4A1 patients, this is not clearly quantifiable. There are minimal data in the literature on the subject. COL4A1 mutations should not be a contraindication for presurgical evaluation. Each patient should be individually evaluated and assessed, risks and benefits were carefully weighed, and informed decisions were reached after thorough discussions with patients and families.

Nitric oxide (NO) is a compound with both protective and damaging effects on neurons. Quantification of NO metabolites in humans is limited by sample contamination with blood. In vivo cerebral microdialysis may offer an alternative approach as sampling of extracellular fluid (ECF) adjacent to neurons becomes possible. We investigate the prognostic value of brain ECF NO metabolites in patients with traumatic brain injury (TBI). A prospective case cohort of 195 ECF samples collected from 11 cases over 4 days following TBI was collected. Nitrate and nitrite concentrations ([NO x ]) were quantified using a vanadium-based colorimetric assay. Early ECF [NO x ] (

In a case study, the authors report an increase in phosphorylated neurofilament heavy chain, a marker of neuroaxonal damage, in the plasma of a blast-exposed patient immediately after injury. They suggest that this phosphoprotein may be a useful body fluid indicator of acute blast traumatic brain injury.

The use of a mathematical model of cerebral physiology and metabolism may aid the interpretation of experimentally measured data. In this study, model outputs of tissue oxygen saturation (TOS) and velocity of blood in the middle cerebral artery (Vmca) were compared with experimentally measured signals (TOS using near infrared spectroscopy and Vmca using transcranial Doppler) acquired during hypercapnia in healthy volunteers. Initially, some systematic discrepancies between predicted and measured values of these variables were identified. The model was optimised to best fit the measured data by adjusting model parameters. To improve the fit, three additional model mechanisms were considered. These were: an extracerebral contribution to TOS, a change in venous volume with CO2 levels, and a change in oxygen consumption with CO2 levels. Each mechanism, when used alone, improved the fit of the model to the data, although significant parameter changes were necessary. It is likely that a combination of these mechanisms will improve the success of modelling of TOS and Vmca changes during hypercapnia.

The use of a mathematical model of cerebral physiology and metabolism may aid the interpretation of experimentally measured data. In this study, model outputs of tissue oxygen saturation (TOS) and velocity of blood in the middle cerebral artery (Vmca) were compared with experimentally measured signals (TOS using near-infrared spectroscopy and Vmca using transcranial Doppler) acquired during hypercapnia in healthy volunteers. Initially, some systematic discrepancies between predicted and measured values of these variables were identified. The model was optimised to best fit the measured data by adjusting model parameters. To improve the fit, three additional model mechanisms were considered. These were: an extracerebral contribution to TOS, a change in venous volume with CO2 levels and a change in oxygen consumption with CO2 levels. Each mechanism, when used alone, improved the fit of the model to the data, although significant parameter changes were necessary. It is likely that a combination of these mechanisms will improve the success of modelling of TOS and Vmca changes during hypercapnia.

Using broadband near-infrared spectroscopy (NIRS) and cerebral microdialysis (MD),we investigated cerebral cellularmetabolismand mitochondrial redox states, following hypercapnoea in 6 patients with traumatic brain injury (TBI). In all patients hypercapnoea increased intracranial pressure and cerebral blood flow velocity measuredwith transcranialDoppler.Despite the likely increase in cerebral oxygen delivery, we did not see an increase in the oxidation status of cytochrome-c-oxidase [oxCCO] in every patient. Analysis of the NIRS data demonstrated two patterns of the changes; Group A (n = 4) showed an increase in [oxCCO] of 0.34(± 0.34)µM and Group B (n = 2) a decrease of 0.40(± 0.41)µM. Although no obvious association was seen between the Δ[oxCCO] and the MD, measured changes in lactate and pyruvate concentrations. Furtherwork usingmodel informed data interpretationmay be helpful in understanding the multimodal signals acquired in this heterogeneous patient group.

Recurrent laryngeal nerve (RLN) palsy is a recognised complication of anterior cervical discectomy (ACD) surgery. We report our experience of intra-operative neuromonitoring using RLN stimulation in 19 patients undergoing ACD surgery. This simple and safe technique has the potential to reduce the incidence of RLN palsy in this patient group.

This study investigates the relationship between changes in brain tissue haemodynamics, oxygenation and oxidised cytochrome-c-oxidase ([oxCCO]) in the adult brain during hyperoxia and hypercapnea. 10 healthy volunteers were studied. We measured the mean blood flow velocity of the right middle cerebral artery (Vmca) with transcranial Doppler (TCD) and changes in concentrations of total haemoglobin ([HbT]=[HbO2]+[HHb]), haemoglobin difference ([Hbdiff]=[HbO2]-[HHb]) and [oxCCO] with broadband near-infrared spectroscopy (NIRS). We also measured the absolute tissue oxygenation index (TOI) using NIR spatially resolved spectroscopy. During hyperoxia there was an increase in TOI (2.33 +/- 0.29%), [Hbdiff] (4.57 +/- 1.27 microM) and in the oxidation of [oxCCO] (0.09 +/- 0.12 microM); but a reduction in Vmca (5.85 +/- 4.85%) and HbT (1.29 +/- 0.91 microM). During hyperoxia there was a positive correlation between [oxCCO] and TOI and [Hbdiff] (r=0.83 and r=0.95) and a negative association between [oxCCO] and Vmca and [HbT] (r=-0.74 and r=-0.87). During hypercapnea there was an increase in TOI (2.76 +/- 2.16%), [Hbdiff] (7.36 +/- 2.64), [HbT] (2.61 +/- 2.7 microM), Vmca (14.92 +/- 17.5%) and in the oxidation of [oxCCO] (0.25 +/- 0.17 microM). Correlation analysis shows that there was association between [oxCCO] and TOI, [Hbdiff] and [HbT] (r=0.83, r=0.93 and r=0.82) but not with Vmca (r=0.33). We conclude that an increase in [oxCCO] was seen during both challenges and it was highly associated with brain tissue oxygenation.

Object Traumatic brain injury (TBI) is associated with depressed aerobic metabolism and mitochondrial dysfunction. Normobaric hyperoxia (NBH) has been suggested as a treatment for TBI, but studies in humans have produced equivocal results. In this study the authors used brain tissue O2 tension measurement, cerebral microdialysis, and near-infrared spectroscopy to study the effects of NBH after TBI. They investigated the effects on cellular and mitochondrial redox states measured by the brain tissue lactate/pyruvate ratio (LPR) and the change in oxidized cytochrome c oxidase (CCO) concentration, respectively. Methods The authors studied 8 adults with TBI within the first 48 hours postinjury. Inspired oxygen percentage at normobaric pressure was increased from baseline to 60% for 60 minutes and then to 100% for 60 minutes before being returned to baseline for 30 minutes. Results The results are presented as the median with the interquartile range in parentheses. During the 100% inspired oxygen percentage phase, brain tissue O2 tension increased by 7.2 kPa (range 4.5–9.6 kPa) (p < 0.0001), microdialysate lactate concentration decreased by 0.26 mmol/L (range 0.0–0.45 mmol/L) (p = 0.01), microdialysate LPR decreased by 1.6 (range 1.0–2.3) (p = 0.02), and change in oxidized CCO concentration increased by 0.21 μmol/L (0.13–0.38 μmol/L) (p = 0.0003). There were no significant changes in intracranial pressure or arterial or microdialysate glucose concentration. The change in oxidized CCO concentration correlated with changes in brain tissue O2 tension (rs= 0.57, p = 0.005) and in LPR (rs= −0.53, p = 0.006). Conclusions The authors have demonstrated oxidation in cerebral cellular and mitochondrial redox states during NBH in adults with TBI. These findings are consistent with increased aerobic metabolism and suggest that NBH has the potential to improve outcome after TBI. Further studies are warranted.

Recent advances in near-infrared spectroscopy (NIRS) allow measurements of absolute tissue oxygen saturation (TOI) using spatially resolved spectroscopy (SRS), while enabling better depth sensitivity. However concerns remain regarding the relative contribution of the extracranial circulation to the cerebral NIRS TOI signal. In this study we investigated this during a period of selective rise in cerebral blood flow (CBF) produced by the administration of acetazolamide (ACZ) in 10 healthy volunteers. A two channel spectrometer (NIRO 300, Hamamatsu Photonics KK) was used to measure absolute cerebral TOI over the frontal cortex using the SRS technique using an optode spacing of 5 cm and 1.5 cm for channel 1 and 2 respectively. After ACZ administration we were able to observe a significant increase in the velocity of middle cerebral artery (V(mca), measured with the transcranial Doppler (TCD)) which was accompanied by an increase in TOI as monitored by the NIRO 300 with an optode spacing of 5 cm but not with an optode spacing of 1.5 cm. Furthermore a direct relationship was seen between the V(mca) and the TOI measured at 5 cm optode spacing. This work suggests that using this commercial NIRS instrument with an optode spacing of 5 cm one is able to detect the intracranial changes.

Oxy- (HbO2) and deoxy- (HHb) haemoglobin signalsmeasured by near infrared (NIR) spectroscopy over the human frontal lobes frequently contain respiratory and low frequency oscillations (LFOs). It has been suggested previously that venous oxygen saturation (SvO2) can be calculated from these respiratory oscillations. In this paper, we investigated the use of a Fourier transform based algorithm to calculate an oxygen saturation measure known as SoscO2 which may be a close estimate of the underlying SvO2. SoscO2 was calculated using three different frequency ranges, (1) respiratory oscillations only, (2) LFOs only, and (3) both respiratory oscillations and LFOs. At each frequency range SoscO2 was calculated using either (1) the modified Beer-Lambert law (MBL) or (2) spatially resolved spectroscopy (SRS). In total six different measurements of SoscO2 were investigated here. Experiments were performed in six adult ventilated patients with traumatic brain injury. The patients’ inspired oxygen fraction (FiO2) was raised in two hyperoxic phases. The calculated SoscO2 values were compared with other cerebral oxygenation measures including an intraparenchymal catheter based brain tissue oxygen tension (PbrO2) and the NIR based tissue oxygenation index (TOI). It was found that the SoscO2 calculated using the combined respiratory and LFO frequency range and the SRS method resulted in the highest detection rates of hyperoxic changes.This measure of SoscO2 may provide a viable, continuous, non invasive, bedside measure of cerebral venous oxygen saturation.

It has been suggested that changes in oxidised cytochrome c oxidase concentration ([oxCCO]) measured using cerebral near infrared spectroscopy (NIRS) may be algorithm artefacts. We examine the change in near infrared (NIR) attenuation by the healthy adult brain (n=10) during hypoxaemia. Broadband spectroscopic data were collected during normoxia, and hypoxaemia. The UCLn algorithm was used to fit (a) oxy- (HbO2) and deoxy-haemoglobin (HHb) spectra (2 component fit), and (b) HbO2, HHb and oxidised-reduced cytochrome c oxidase difference spectra (3 component fit) to themean change inNIR attenuation between baseline and hypoxaemia. The sum of squares of the residuals was 100×10−7 OD2 for the 2 component fit and 8×10−7 OD2 for the 3 component fit, and the two sets of residuals differed from each other (p=0.0003). We compare experimental and simulated data and suggest that the 2 component residuals indicate a change in [oxCCO]. Changes in near infrared attenuation by the healthy adult brain during hypoxaemia cannot be accounted for solely by changes in oxyand deoxy-haemoglobin concentrations. Including [oxCCO] in the algorithm improves its fit quality. These data suggest that changes in cerebral cytochrome c oxidase redox occur during hypoxaemia and that they can be detected using NIRS.

Recent advances in near-infrared spectroscopy (NIRS) allow measurements of absolute tissue oxygen saturation (TOI) using spatially resolved spectroscopy (SRS), while enabling better depth sensitivity. However concerns remain regarding the relative contribution of the extracranial circulation to the cerebral NIRS TOI signal. In this study we investigated this during a period of selective rise in cerebral blood flow (CBF) produced by the administration of acetazolamide (ACZ) in 10 healthy volunteers. A two channel spectrometer (NIRO 300, Hamamatsu Photonics KK) was used to measure absolute cerebral TOI over the frontal cortex using the SRS technique using an optode spacing of 5 cm and 1.5 cm for channel 1 and 2 respectively. After ACZ administration we were able to observe a significant increase in the velocity of middle cerebral artery (Vmca, measured with the transcranial Doppler (TCD)) which was accompanied by an increase in TOI as monitored by the NIRO 300 with an optode spacing of 5 cm but not with an optode spacing of 1.5 cm. Furthermore a direct relationship was seen between the Vmca and the TOI measured at 5 cm optode spacing. This work suggests that using this commercial NIRS instrument with an optode spacing of 5 cm one is able to detect the intracranial changes.

We have previously reported changes in the concentrations of oxy- (δ[HbO2]) deoxy- (δ[HHb]) and total haemoglobin (δ[HbT]=δ[HbO2]+δ[HHb]) measured using near infrared spectroscopy (NIRS) over the frontal cortex (FC) during an anagram solving task. These changes were associated with a significant increase in both mean blood pressure (MBP) and heart rate (HR). The aim of this study was to investigate whether the changes in MBP previously recorded during an anagram solving task produces associated changes in scalp blood flow (flux) measured by laser Doppler and whether any changes are seen in NIRS haemodynamic measurements over a control region of the brain (motor cortex: MC). During the 4-Letter anagram task significant changes were observed in theδ[HbO2],δ[HHb] andδ[HbT] in both the frontal and motor cortex (n=11, FC p

The near-IR cytochrome c oxidase (CCO) signal has potential as a clinical marker of changes in mitochondrial oxygen utilization. We examine the CCO signal response to reduced oxygen delivery in the healthy human brain. We induced a reduction in arterial oxygen saturation from baseline levels to 80% in eight healthy adult humans, while minimizing changes in end tidal carbon dioxide tension. We measured changes in the cerebral concentrations of oxidized CCO (Delta[oxCCO]), oxyhemoglobin (Delta[HbO(2)]), and deoxyhemoglobin (Delta[HHb]) using broadband near-IR spectroscopy (NIRS), and estimated changes in cerebral oxygen delivery (ecDO(2)) using pulse oximetry and transcranial Doppler ultrasonography. Results are presented as median (interquartile range). At the nadir of hypoxemia ecDO(2) decreased by 9.2 (5.4 to 12.1)% (p0.0001), Delta[oxCCO] decreased by 0.24 (0.06 to 0.28) micromoles/l (p0.01), total hemoglobin concentration increased by 2.83 (2.27 to 4.46) micromoles/l (p0.0001), and change in hemoglobin difference concentration (Delta[Hbdiff]=Delta[HbO(2)]-Delta[HHb]) decreased by 12.72 (11.32 to 16.34) micromoles/l (p0.0001). Change in ecDO(2) correlated with Delta[oxCCO] (r=0.78, p0.001), but not with either change in total hemoglobin concentration or Delta[Hbdiff]. This is the first description of cerebral Delta[oxCCO] during hypoxemia in healthy adults. Studies are ongoing to investigate the clinical relevance of this signal in patients with traumatic brain injury.

To investigate the accuracy of measuring cerebral blood flow (CBF) using a bolus injection of indocyanine green (ICG) detected by near infrared spectroscopy in adult human heads, simulations were performed using a two layered model, representing the extracerebral and intracerebral layers. Modelled optical data were converted into tissue ICG concentration using either the one detector modified Beer Lambert law (MBLL) method, or the two detector partial pathlength (PPL) method. CBFs were estimated using deconvolution and blood flow index techniques respectively. Using the MBLL method, CBFs were significantly underestimated but the PPL method improved their accuracy and robustness, especially when used as relative measures. Dispersion of the arterial input function also affected the CBF estimates.

Disorders of sodium and water balance are common in critically ill adult neurologic patients. Normal aspects of sodium and water regulation are reviewed. The etiology of possible causes of sodium disturbance is discussed in both the general inpatient and the neurologic populations. Areas of importance are highlighted with regard to the differential diagnosis of sodium disturbance in neurologic patients, and management strategies are discussed. Specific discussions of the etiology, diagnosis, and management of cerebral salt wasting syndrome, the syndrome of inappropriate antidiuretic hormone secretion, and central diabetes insipidus are presented, as well as the problems of overtreatment. The importance of diagnosis at an early stage of these diseases is stressed, with a recommendation for conservative management of milder cases. Copyright © 2005 by Lippincott Williams & Wilkins.

Using the Fick principle and a finite element model of light distribution, ICG boluses were simulated in a head model, showing measurable changes in cerebral blood flow using NIR surface measurements despite the superficial contamination.

Management of a child with club foot deformity that recurs after an apparently successful posteromedial soft tissue release remains a challenge. Revision surgery is often attempted, but this carries a high risk of significant scarring or neurovascular complications. We have treated 3 children (3 feet) with relapsed club foot and fixed deformities, using Botulinum toxin A (BTX-A) injection into muscle groups clinically thought to be responsible for recurrent deformity, followed by moulded plaster casts. Two cases have maintained a good foot position with an minimum follow-up of 18 months, and one other is also doing well having had a tibialis anterior tendon transfer as well as the BTX-A therapy. In our limited experience, targeted BTX-A injection with plaster casting has been safe, and may obviate the need for major revision surgery in a proportion of cases with recurrent club foot deformity following previous posteromedial soft tissue release.