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Thyrotoxic periodic paralysis (TPP) is an acute complication of hyperthyroidism. Thyrotoxic periodic paralysis is treatable, and the management consists of potassium correction, beta-blockers, and antithyroid drug (ATD) therapy. While TPP is well described in the literature, we describe a case of TPP with urticarial dermographia (UD) that resolved with a short course of antihistamines while continuing ATD therapy. To the best of our knowledge, this is the first reported case of UD after methimazole (MMI) therapy in a TPP patient. A 25-year-old Cambodian active duty male with no significant past medical history presented to the emergency department with acute loss of lower extremity muscle tone with hypokalemia in the setting of previously undiagnosed Graves' disease (GD). He was started on MMI but within 2 weeks developed a rash consistent with UD. This was successfully treated with a second-generation antihistamine while continuing his MMI. Thyrotoxic periodic paralysis is primarily treated by controlling the underlying thyroid disease causing paralysis. Methimazole is commonly chosen as a treatment due to its rapid efficacy and long duration of action. However, adverse effects like UD can occur. Current recommendations are that minor cutaneous reactions can be treated with antihistamines for the management of Graves' disease. However, this case and others show that even moderate reactions can be managed in this manner. In a patient with TPP with UD after treatment with MMI, it is reasonable to attempt a trial of antihistamine before changing to another ATD. [ABSTRACT FROM AUTHOR]

Ectopic prolactin-secreting microadenomas are rare and management is often surgical in contrast to intrasellar pituitary prolactin-secreting microadenomas. We present a case of ectopic dopamine-resistant microprolactinoma treated with cabergoline which led to symptom resolution, hormonal remission, and cystic degeneration of the tumor. A 30-year-old active duty male presented with a chief complaint of inability to maintain an erection for 6 months. Initial workup revealed suppressed serum testosterone of 128.60 ng/ml with an elevated prolactin level at 275.10 ng/ml. Pituitary magnetic resonance imaging showed a small mass measuring 9 mm in the left cavernous sinus. Medical management was initiated with cabergoline, which was titrated over the course of a year from 0.5 mg a week to 3.5 mg a week at its peak before being weaned off completely at 54 months. After treatment, the patient's symptoms resolved, his prolactin decreased to 29.5 ng/ml, near-normal, and his tumor had decreased size with cystic degeneration. Management for any prolactinoma has three primary goals: remittance of symptoms, decrease in prolactin levels, and decrease in tumor size. These are achieved through primarily medical management or surgery. Even though ectopic microprolactinomas are still frequently addressed surgically, this case shows that medical therapy can successfully treat ectopic prolactin-secreting pituitary microadenomas even in cases of dopamine resistance. [ABSTRACT FROM AUTHOR]

One important cause of retinal haemorrhages (RHs) in children is abusive head trauma (AHT). Our programme of research was conducted on children admitted to hospital over a seven‐year period who had RHs as part of their clinical presentation. This paper summarises important findings from previous publications. As a prerequisite, two basic studies were necessary: (i) a method of reporting the precise location of the RH in the retina; and (ii) defining a simple clinical classification of RHs based on the appearance of the retinal layer involved. Because raised intracranial pressure (RICP) is a frequent secondary brain insult following serious adult head injury, causing hypoxic‐ischaemic injury with a resultant poor outcome, it was considered whether such RICP might also cause RHs in children. Detailed, state‐of‐the‐art monitoring methods were used to investigate this relationship along with retinal imaging. Methodical documentation of the type, area and lifespan of RHs meant that it was possible to address the question of predicting AHT from RH numbers and characteristics, and to describe not only the duration of different layer haemorrhages, but also a previously unreported observation that some RHs transiently enlarge over two to three days before resolving normally. 'One important cause of retinal haemorrhages (RHs) in children is abusive head trauma' Key Practitioner Messages: A new retinal zone classification for research and legal purposes has been developed, as well as a simplified five‐point working classification of RHs, based on existing fundoscopic descriptions.In this cohort study, a young age and a high 'dot‐blot' count (>25 intraretinal haemorrhages) are strong predictors of AHT.There is a complex association between the burden of intracranial pressure insult and RHs.Time to resolution of different RHs has been calculated using two‐dimensional RH area pixel counts from sequential retinal imaging. Two patterns of resolution are reported. [ABSTRACT FROM AUTHOR]

Objective. There is limited information regarding the long-term outcome of inflicted traumatic brain injury (TBI), including shaken infant syndrome. The purpose of this study was to describe the long-term neurologic, behavioral, and cognitive sequelae seen in this population. Methods. A cross-sectional and prospective longitudinal study was conducted of 25 children with inflicted TBI in Scotland between 1980 and 1999. After consent was obtained, neurologic and cognitive examinations were performed on all participants and sequentially in the prospective cohort. Two global outcome measures were used: Glasgow Outcome Score (GOS) and Seshia's outcome score. Cognitive outcome was assessed using the Bayley Scales of Infant Development, British Ability Scales, and the Vineland Adaptive Behavior Scales. Results. The mean length of follow-up was 59 months. A total of 68% of survivors were abnormal on follow-up, 36% had severe difficulties and were totally dependant, 16% had moderate difficulties, and 16% had mild difficulties on follow-up. A wide range of neurologic sequelae were seen, including motor deficits (60%), visual deficits (48%), epilepsy (20%), speech and language abnormalities (64%), and behavioral problems (52%). There was a wide range of cognitive abilities: the mean psychomotor index, 69.9 (SD: [+ or -] 25.73); and mean mental development index, 74.53 (SD: [+ or -] 28.55). Adaptive functioning showed a wide range of difficulties across all domains: communication domain (mean: 76.1; SD: [+ or -] 25.4), Daily living skills domain (mean: 76.9; SD: [+ or -] 24.3), and socialization domain (mean: 79.1; SD: [+ or -] 23.1). Outcome was found to correlate with the Pediatric Trauma Score and the Glasgow Coma Score but did not correlate with age at injury or mechanism of injury. Conclusions. Inflicted TBI has a very poor prognosis and correlates with severity of injury. Extended follow-up is necessary so as not to underestimate problems such as specific learning difficulties and attentional and memory problems that may become apparent only once the child is in school. Behavioral problems are present in 52% and begin to manifest clinically between the second and third years of life, although the consequences of frontal lobe injury may be underestimated unless follow-up is extended into adolescence and early adulthood. Pediatrics 2005;116:e174-e185. URL: www.pediatrics.org/ cgi/doi/10.1542/peds.2004-2739; behavior disorders/problems, head trauma, infants, neurobehavioral outcomes, shaken baby syndrome.

Background: Preterm infants receiving supplemental oxygen therapy experience frequent fluctuations in their blood oxygen levels, the magnitude of which has been associated with the incidence and severity of retinopathy of prematurity in such infants. Objective: Our objective was to investigate in a relevant animal model whether the immature brain with its poorly vascularised white matter might also be susceptible to injury when exposed to such fluctuations in blood oxygen. Methods: Newborn rats were reared in an atmosphere in which a computer reproduced the oxygen fluctuations derived from the transcutaneous oxygen levels of a 24-week preterm infant who had developed severe retinopathy. Following 14 days of exposure, we measured the expression of active caspase-3, myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in the brains comparing with rat pups raised in room air. Results: Compared to room air controls, at day 14, the expression of active caspase-3 was increased by up to 162% (significant increase in 7 of 9 regions), MBP decreased by up to 70% (significant in the hypothalamus only) and GFAP increased by up to 103% (significant in 6 of 7 regions. On day 21, following 7 days of reparative recovery, GFAP levels in most areas of oxygen-exposed brains had returned to near control levels. There were no longer significant differences in caspase-3 levels apart from the cerebral cortex, cerebellum and striatum. In contrast, MBP expression was now much higher in most regions of the treated brains compared to controls. Conclusion: We conclude that fluctuations in blood oxygen, observed in preterm survivors, may constitute a source of injury to the white matter and corpus striatum of the developing brain and contribute to the neurological sequelae in extremely premature infants. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency may present with variable neurological manifestations. Radiological features include white matter changes (leukoencephalopathy). Clinical, biochemical, and radiological response to treatment may again be variable. Here we present a 12-year follow-up of two siblings on the same treatment regimen, with contrasting long-term findings. The first patient, a female presenting at 15 years, showed a good clinical response, substantial intellectual gain, and complete reversal of leukoencephalopathy. Her brother presented at 13 years 9 months and showed limited clinical and cognitive improvement with persistence of the leukoencephalopathy. Both siblings showed a partial biochemical response to treatment. [ABSTRACT FROM AUTHOR]

The literature regarding the outcome of non-accidental head injury (NAHI) is scarce and lacks specific detail even though it is generally considered to be poor. The purpose of this study is to review the literature to date and report the neurological outcome of these children in detail. Twenty-five children were enrolled and 68% of children were neurologically abnormal at an average follow-up of 59 months. A wide range of abnormalities and outcomes was seen. Speech and language difficulties were present in 64% including autistic spectrum disorder. Cranial nerve abnormalities were present in 20%. Visual deficits and epilepsy compounded learning difficulties in 25% of survivors. Consent for follow-up was more likely to be obtained where the perpetrator was known. The spectrum and degree of severity of neurological abnormalities in survivors of NAHI is extremely variable, with the majority of these children being moderate or severely abnormal. These children require the support of a multi-disciplinary team in the community. Further study regarding the process of follow-up, where complex medicolegal issues exist, are needed in order to facilitate maximum neurological development. [ABSTRACT FROM AUTHOR]

Transcranial Doppler ultrasound monitoring of cerebral blood flow velocity (CBFV) was performed on 17 children (age range 8 days to 6 years) with pyogenic meningitis. Serial measurements of the peak systolic, end diastolic, mean flow velocity, and resistance index (equal to peak systolic velocity minus end diastolic velocity divided by peak systolic velocity) were obtained over the period of their hospital admission. In all 16 survivors there was a significant decrease in the final resistance index compared with the initial resistance index due to a significant increase in the end diastolic velocity. There was a significant increase in the final mean flow velocity. In four patients the decrease in intracranial pressure and increase in cerebral perfusion pressure after mannitol infusions was accompanied by a corresponding decrease in resistance index and increase in mean flow velocity. A pressure passive CBFV response with a significant linear correlation for resistance index/mean arterial pressure may suggest a loss of cerebrovascular autoregulation. These results suggest that in the early phase increased cerebrovascular resistance may contribute to a relative impairment of cerebral perfusion. Non-invasive monitoring by transcranial Doppler ultrasound may be helpful for early detection of deterioration in cerebral haemodynamic trends. [ABSTRACT FROM AUTHOR]

Purpose: To examine the diagnostic ability of saccadic vector optokinetic perimetry (SVOP), a new eye tracking perimeter, by assessing its capacity to differentiate healthy and glaucomatous participants, and to compare performance to standard automated perimetry (SAP). Methods: A prospective case‐control study including patients with glaucoma and healthy volunteers recruited from the glaucoma clinic at a university hospital and from the Scottish Health Research Register (SHARE). Participants underwent a comprehensive ophthalmic examination and performed SAP and SVOP in both eyes with the order of testing randomised. Results: 61 eyes of 31 participants with glaucoma and 47 eyes of 24 healthy participants were included in the study. Average SAP mean deviation (MD) in glaucomatous eyes was ‐8.72 ± 7.37 dB, with average SAP and SVOP sensitivities of 23.28 ± 0.89 dB and 22.1 ± 4.25 dB respectively. There was strong correlation between average SAP and SVOP sensitivities (r = 0.951 , P<0.001). On average, SAP sensitivity was 1.16 ± 1.43 dB higher than SVOP sensitivity, with 95% limits of agreement of ‐1.64 to 3.96 dB. SVOP average sensitivity had excellent ability to differentiate healthy and glaucomatous eyes with an AUC of 0.90 (95% CI 0.84 to 0.96), which was not significantly different to the performance of SAP average sensitivity (AUC = 0.92, 95% CI.0.86 to 0.97, P = 0.60) (Figure 6). SVOP had 85.2% sensitivity for 80% specificity, compared to 86.9% sensitivity for 80% specificity for SAP. Conclusions: The results of this study suggest that eye tracking perimetry using SVOP could offer a feasible alternative to SAP for detection of glaucoma. Overall, there was good agreement between differential light sensitivity values measured using SVOP and those measured using SAP, and average SVOP and SAP sensitivities had similarly good ability to differentiate glaucomatous and healthy eyes. [ABSTRACT FROM AUTHOR]

Background: This study utilized an existing national database of cases of non-accidental head injury (NAHI; also called inflicted traumatic brain injury [inflicted TBI] and shaken baby syndrome [SBS]) in Scotland to report the incidence, confidence intervals, and demography of such cases in Southeast Scotland. Methods: This prospective population-based study was conducted from January 1998 to September 2006. Data from the Lothian region of Scotland, where there is known full ascertainment of infant head injuries, including NAHI, have been used to calculate the incidence rate for this region of Scotland, with government statistics providing the normal annual infant population as the denominator. A new Scottish Index of Multiple Deprivation (SIMD), which assesses a very focused area (data zone population size=750) and provides novel information about social demography for education, housing, employment, health, crime, income, and geographic accessibility to services, was applied to the identified cases of NAHI during this study period. Results: The mean incidence of NAHI in southeast Scotland for 8.75 years was 33.8/100,000 infants per year. The cases of NAHI were mostly located in the lowest 1 (or 2) quintiles for all SIMD domains (education, housing, employment, health, crime, income), although they had good accessibility to medical and other community services. Conclusions: The incidence rates from this prospective study for NAHI are considerably higher than other published UK surveys and are not considered to reflect a cluster effect. The perpetrators in this study fit a strongly skewed profile aggregating to the lowest socioeconomic groups in the community. [Copyright &y& Elsevier]

A letter to the editor is presented in response to a letter on the occurrence of neurological deficits in children due to shaken baby syndrome.

Purpose: To examine the feasibility of saccadic vector optokinetic perimetry (SVOP), an automated eye tracking perimeter, as a tool for visual field (VF) assessment in infants., Methods: Thirteen healthy infants aged between 3.5 and 12.0 months were tested binocularly using an adapted SVOP protocol. SVOP uses eye tracking technology to measure gaze responses to stimuli presented on a computer screen. Modifications of SVOP for testing infants included adjusting the fixation target to display a short animation, increasing the stimulus size to equivalent to Goldmann V, and introducing a tiered test pattern strategy. Binocular, single-quadrant confrontation VF testing and Keeler preferential looking cards visual acuity testing was also performed., Results: Using multiple test attempts when required, all but the youngest infant (12 of 13 [92.3%]) successfully completed a 4-point screening test. Seven infants (53.8%) successfully completed the 12-point test, four (30.8%) successfully completed the 20-point test, and three (23.1%) successfully completed the 40-point test. The effect of multiple test attempts and the complexity of the test pattern (number of test points) on performance was investigated, including test completion rate, percentage of correctly seen stimuli, and average time per tested stimulus., Conclusions: The modified SVOP test strategy allowed successful assessment of binocular VFs in healthy infants. Future data collection from larger cohorts of infants is needed to derive normative limits of detection and assess accuracy in detecting and monitoring infant VF abnormalities., Translational Relevance: Eye tracking perimetry may provide a useful method of automated VF assessment in infants.

Objective: To determine the time to resolution of different-layered retinal haemorrhages (RHs), and to describe the main patterns of their resolution in a group of children with encephalopathies., Methods and Analysis: From a prospective study of 114 children with traumatic and non-traumatic encephalopathies, 429 selected individual RHs (iRHs) from 18 children were serially imaged from admission using a RetCam. Photoshop and Scion Imaging software allowed calculation of RH area in pixels., Results: Two patterns of the resolution were recognised on the basis of area measurements: a progressive decrease (pattern A, 60% of iRHs), and a form of asymmetrical decay in which iRHs first increased in size before then progressively decreasing (pattern B, 35% of iRHs). Within the pattern A group, the Kaplan-Meier median survival time (MST) (95% CI) was 10 (9.3 to 10.7) days for intra-RHs (IRHs) and 38 (10.8 to 65.2) days for pre-RHs (PRHs), log rank (Mantel-Cox) p=0.001. The mean percentage reduction in area per day was 12.5% for all iRHs, 14.5% for IRHs and 6.3% for PRHs., Conclusion: Serial area measurements of iRHs revealed that 35% haemorrhages became temporarily larger before decreasing to resolution. Serially imaged selected RHs showed a longer MST for PRHs than for IRHs., Competing Interests: Competing interests: None declared.

Purpose: We evaluated threshold saccadic vector optokinetic perimetry (SVOP) and compared results to standard automated perimetry (SAP)., Methods: A cross-sectional study was done including 162 subjects (103 with glaucoma and 59 healthy subjects) recruited at a university hospital. All subjects underwent SAP and threshold SVOP. SVOP uses an eye tracker to monitor eye movement responses to stimuli and determines if stimuli have been perceived based on the vector of the gaze response. The test pattern used was equivalent to SAP 24-2 and stimuli were presented at Goldmann III. Average and pointwise sensitivity values obtained from both tests were compared using Pearson's correlation coefficient. Two versions of SVOP were evaluated., Results: A total of 124 tests were performed with SAP and SVOP version 2. There was excellent agreement between mean threshold values obtained using SVOP and SAP ( r = 0.95, P < 0.001). Excluding the blind spot, correlation between SVOP and SAP individual test point sensitivity ranged from 0.61 to 0.90, with 48 of 54 (89%) test points > 0.70. Overall SVOP showed good repeatability with a Pearson correlation of 0.88. The repeatability on a point-by-point basis ranged from 0.66 to 0.98, with 45 of 54 points (83%) > 0.80. Repeatability of SAP was 0.87, ranging from 0.69 to 0.96, with 47 of 54 (87%) points > 0.80., Conclusion: Eye-tracking perimetry is repeatable and compares well with the current gold standard of SAP. The technique has advantages over conventional perimetry and could be useful for evaluating glaucomatous visual field loss, particularly in patients who may struggle with conventional perimetry., Translational Relevance: Suprathreshold SVOP already is in the field. To our knowledge, this is the first report of threshold SVOP and provides a benchmark for future iterations.

Purpose: We compared patterns of visual field loss detected by standard automated perimetry (SAP) to saccadic vector optokinetic perimetry (SVOP) and examined patient perceptions of each test., Methods: A cross-sectional study was done of 58 healthy subjects and 103 with glaucoma who were tested using SAP and two versions of SVOP (v1 and v2). Visual fields from both devices were categorized by masked graders as: 0, normal; 1, paracentral defect; 2, nasal step; 3, arcuate defect; 4, altitudinal; 5, biarcuate; and 6, end-stage field loss. SVOP and SAP classifications were cross-tabulated. Subjects completed a questionnaire on their opinions of each test., Results: We analyzed 142 (v1) and 111 (v2) SVOP and SAP test pairs. SVOP v2 had a sensitivity of 97.7% and specificity of 77.9% for identifying normal versus abnormal visual fields. SAP and SVOP v2 classifications showed complete agreement in 54% of glaucoma patients, with a further 23% disagreeing by one category. On repeat testing, 86% of SVOP v2 classifications agreed with the previous test, compared to 91% of SAP classifications; 71% of subjects preferred SVOP compared to 20% who preferred SAP., Conclusions: Eye-tracking perimetry can be used to obtain threshold visual field sensitivity values in patients with glaucoma and produce maps of visual field defects, with patterns exhibiting close agreement to SAP. Patients preferred eye-tracking perimetry compared to SAP., Translational Relevance: This first report of threshold eye tracking perimetry shows good agreement with conventional automated perimetry and provides a benchmark for future iterations.

Purpose: To evaluate feasibility, accuracy, and repeatability of suprathreshold Saccadic Vector Optokinetic Perimetry (SVOP) by comparison with Humphrey Field Analyzer (HFA) perimetry., Methods: The subjects included children with suspected field defects ( n = 10, age 5-15 years), adults with field defects ( n = 33, age 39-78 years), healthy children ( n = 12, age 6-14 years), and healthy adults ( n = 30, age 16-61 years). The test protocol comprised repeat suprathreshold SVOP and HFA testing with the C-40 test pattern. Feasibility was assessed by protocol completeness. Sensitivity, specificity, and accuracy of SVOP was established by comparison with reliable HFA tests in two ways: (1) visual field pattern results (normal/abnormal), and (2) individual test point outcomes (seen/unseen). Repeatability of each test type was assessed using Cohen's kappa coefficient., Results: Of subjects, 82% completed a full protocol. Poor reliability of HFA testing in child patients limited the robustness of comparisons in this group. Sensitivity, specificity, and accuracy across all groups when analyzing the visual field pattern results was 90.9%, 88.5%, and 89.0%, respectively, and was 69.1%, 96.9%, and 95.0%, respectively, when analyzing the individual test points. Cohen's kappa coefficient for repeatability of SVOP and HFA was excellent (0.87 and 0.88, respectively) when assessing visual field pattern results, and substantial (0.62 and 0.74, respectively) when assessing test point outcomes., Conclusions: SVOP was accurate in this group of adults. Further studies are required to assess SVOP in child patient groups., Translational Relevance: SVOP technology is still in its infancy but is used in a number of centers. It will undergo iterative improvements and this study provides a benchmark for future iterations.

Background: Retinal hemorrhages (RHs) occur in inflicted traumatic brain injury (ITBI), accidental traumatic brain injury (ATBI), and some medical conditions, although the reported number, distribution, type, and frequency vary greatly between these different etiologies. We hypothesize that these RH characteristics reliably help to distinguish ITBI from ATBI and nontraumatic etiologies., Methods: A 6-year prospective observational study using wide-field retinal imaging (RetCam) was conducted within 24 hours of admission to PICU, on serially recruited children with traumatic and nontraumatic encephalopathies. "Definite" and "probable" ITBI cases were confirmed by multiagency child protection case conferences. Image analysis used digital color and grayscale images for retinal "zoning" and "layering" of hemorrhages., Results: Significant differences were found between the mean numbers of hemorrhages in ATBI/ITBI, and ITBI/nontraumatic etiologies for the 3 retinal zones (range, P = .003-.009) and for the dot-blot hemorrhages (range P = .001-.002). The mean numbers of RHs per ITBI patient in the peripapillary, macula, and peripheral zones were 14, 28, and 31 respectively. RHs in ATBI were near the optic disc and more superficial than in ITBI, where hemorrhages involved deeper layers (range, P = .003-.039) and were more peripheral (P = .03). The positive predictive value for ITBI in children <3 years with >25 dot-blot (intraretinal) hemorrhages was 93%., Conclusions: This prospective study, which included all potential causes of RHs, with objective retinal methodology, has confirmed that a young age and a high dot-blot count are strong predictors of ITBI. This high predictive value may support medicolegal deliberations.

This study aims to determine if pairing the Glasgow Coma Scale (GCS) with serum biomarker levels may achieve higher outcome predictive values than using either the GCS or biomarker levels alone in childhood brain trauma. Twenty-eight critically ill children with isolated accidental brain trauma were studied in a prospective observational study. The GCS was recorded at various time points post injury. Enzyme-linked immunosorbent assay (ELISA) was used to quantify eight different serum biomarker levels (S100b, NSE, IL-6, IL-8, IL-10, L-selectin, SICAM, and endothelin) on day 1 post injury. The Glasgow Outcome Score (GOS) was used to assess global outcome at 6 months post injury. Outcome predictive values of the GCS, individual biomarker levels, and paired combinations of the GCS and biomarkers were compared using receiver operator characteristic (ROC) curve analysis and its multivariate extension, multivariate ROC curve (MultiROC). When using either the GCS or individual biomarker levels alone to predict unfavorable outcome, only the PICU discharge summated GCS achieved an area under the ROC curve (AUC) of more than 0.95. This high degree of outcome predictability was also achieved by pairing the GCS with a single biomarker level. The most pronounced improvement in outcome prediction was observed by pairing the post-resuscitation summated GCS with the day-1 serum IL-8 level, which increased the AUC from 0.78 to 0.98 and the sensitivity and specificity from 75% to 100% and 96% respectively. Paired combinations of the GCS and serum biomarker levels greatly enhanced the accuracy of post-traumatic unfavorable outcome prediction than may be achieved using either the GCS or individual biomarker levels alone.

Many potential brain trauma biomarkers have been reported, but no previous study has described outcome prediction using combinations of biomarker levels. We aimed to investigate the outcome predictive values of multiple biomarkers from different mediator families and to determine whether combinations of two serum biomarkers may achieve higher outcome predictive values than individual biomarker levels. A prospective observational study was conducted involving 28 children requiring intensive care management following brain trauma. Day 1 post-injury serum concentrations of eight different biomarkers--S100b protein (S100b), neuron-specific enolase (NSE), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble intracellular adhesion molecule (SICAM), L-selectin, and endothelin--were quantified using enzyme-linked immunosorbent assay (ELISA). Global outcome was assessed at 6 months post-injury using the Glasgow Outcome Score (GOS). Receiver operator characteristic curve (ROC) analysis and its multivariate extension, Multivariate ROC (MultiROC), were used to assess the outcome predictive values of the individual and the paired biomarkers. None of the eight biomarkers assessed individually achieved an area under the ROC curve (AUC) of more than 0.95 for predicting unfavorable outcome, but five of the 20 biomarker pairs assessed had this high degree of outcome predictability. Two combinations using S100b as the "screening marker" and either L-selectin or IL-6 as the "varying marker" achieved an AUC of 0.98, and their specificity and sensitivity for unfavorable outcome prediction were 96% and 100%, respectively. Prognostic pairs combining serum levels of two biomarkers (inflammatory mediators and brain-specific proteins) offer better outcome predictive values for unfavorable outcome after childhood brain trauma than may be achieved using individual marker levels.

Objective: To determine how benzodiazepine (BZD) sensitivity testing might be utilized to choose potentially useful antiepileptic drugs., Methods: A retrospective audit of BZD sensitivity testing was carried out on 76 difficult pediatric epileptic cases that attended the Pediatric Neurology services at The Royal Hospital for Sick Children Edinburgh, Scotland from February 2005 to February 2006. The causes and types of epilepsy varied widely, as well as the encephalographic (EEG) findings. The EEG changes post-test are categorized according to the response to BZDs into "complete," "intermediate," "paradoxical" and "absent response." Similarly, the clinical outcomes after changing their antiepileptic medications have different ranges of clinical improvement from "definitive," "partial" and "no improvement.", Results: The largest percentages of definitive improvement are seen in those with complete response. The percentage with clinical improvement tends to decrease a) with increasing numbers and amplitudes of spikes that are resistant to the action of BZD, and b) when there is a paucity of, and different distribution of fast rhythms, indicating non-viability of cortical tissues. High spike density regions in the EEG pre-test that correlate with a specific pathology, and are found post-test to be devoid of fast rhythms, may indicate focally damaged gamma-aminobutyric acid receptor areas., Conclusion: The BZD sensitivity testing may influence the choice of anticonvulsants in the management of epilepsy.

Objective: To report the use of high frequency oscillatory ventilation (HFOV) in two children with severe traumatic brain injury and concurrent lung pathology where conventional mechanical ventilation was ineffective., Design: : Case report., Setting: Regional intensive care unit in a pediatric teaching hospital., Patients: Two severely head-injured children (both with postresuscitation Glasgow Coma Scores of 3), one of whom was age 11 yrs and developed an invasive fungal (rhizomucor) pneumonia, while the other age 5 yrs had bilateral lung contusions. Both were treated according to local head injury guidelines, which included conventional ventilation. Despite increasing conventional ventilatory support, CO2 removal became problematic in both cases, making the intracranial pressure control and consequent maintenance of adequate cerebral perfusion pressure difficult. In both patients, a dramatic reduction in intracranial pressure and improvement in cerebral perfusion pressure was observed soon after the use of HFOV. Additionally, inotropic support was weaned by 50% in both children after commencing HFOV. A significant increase in the mean arterial blood pressure occurred in one child with HFOV., Intervention: Use of HFOV as an alternative to conventional mechanical ventilation., Conclusion: HFOV may have utility in the management of selected cases of severe brain trauma with concurrent lung pathology where conventional ventilation is ineffective.

Summary: Independent component analysis (ICA) has recently been applied to epileptic seizure in the EEG. In this paper, the authors show how the fundamental axioms required for ICA to be valid are broken. Four common cases of childhood seizure are presented and assessed for stationarity and an eigenvalue analysis is applied. In all cases, for the stationary sections of data the eigenvalue analysis yields results that imply the signals are coming from a source-rich environment, thus yielding ICA inappropriate when applied to the four common types of childhood seizure. The results suggest that it is not appropriate to apply ICA or source localization from independent components in these four common cases of epilepsy, because the spurious independent components determined by ICA could lead to a spurious localization of the epilepsy. If surgery were to follow, it could result in the incorrect treatment of a healthy localized region of the brain.