Search

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.

To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate glaucomatous and healthy eyes. A prospective case-control study was performed using a convenience sample recruited from a single university glaucoma clinic and a group of healthy controls. SVOP and standard automated perimetry (SAP) was performed with testing order randomised. The reference standard was a diagnosis of glaucoma based a comprehensive ophthalmic examination and abnormality on standard automated perimetry (SAP). The index test was SVOP. 31 patients with glaucoma and 24 healthy subjects were included. Mean SAP mean deviation (MD) in those with glaucoma was - 8.7 ± 7.4 dB, with mean SAP and SVOP sensitivities of 23.3 ± 0.9 dB and 22.1 ± 4.3 dB respectively. Participants with glaucoma were significantly older. On average, SAP sensitivity was 1.2 ± 1.4 dB higher than SVOP (95% limits of agreement = - 1.6 to 4.0 dB). SVOP sensitivity had good ability to differentiate healthy and glaucomatous eyes with a 95% CI for area under the curve (AUC) of 0.84 to 0.96, similar to the performance of SAP sensitivity (95% CI 0.86 to 0.97, P = 0.60). For 80% specificity, SVOP had a 95% CI sensitivity of 75.7% to 94.8% compared to 77.8% to 96.0% for SAP. SVOP took considerably longer to perform (514 ± 54 s compared to 267 ± 76 s for SAP). Eye tracking perimetry may be useful for detection of glaucoma but further studies are needed to evaluate SVOP within its intended sphere of use, using an appropriate design and independent reference standard.

Precis: Normal age-corrected threshold sensitivity values were determined for a new eye tracking perimeter and compared with standard automated perimetry (SAP)., Purpose: The purpose of this study was to determine threshold visual field sensitivities in normal subjects performing saccadic vector optokinetic perimetry (SVOP), a new eye tracking perimeter., Patients and Methods: A total of 113 healthy participants performed SVOP and SAP in both eyes with the order of testing randomized. The relationship between SAP and SVOP sensitivity was examined using Bland-Altman plots and 95% limits of agreement. The relationship between sensitivity and age was examined by pointwise linear regression and age-corrected normal threshold sensitivities were calculated., Results: After excluding unreliable tests, 97 participants with a mean age of 65.9±10.1 years were included. Average SAP mean deviation was -0.87±1.56 dB, SAP sensitivity was 29.20±1.68 dB and SVOP sensitivity was 32.18±1.96 dB. SVOP had a longer test duration (431±110 compared with 307±42 seconds for SAP, P<0.001). On average, the mean sensitivity obtained using SVOP was 2.98 dB higher than average SAP sensitivity, with 95% limits of agreement of -0.11 to 6.15 dB. For each decade older, SAP sensitivity decreased by 0.93 dB (95% confidence interval: 1.21 to 0.64) and SVOP sensitivity decreased by 1.15 dB (95% confidence interval: 1.47 to 0.84)., Conclusions: The results provide age-corrected normative values for threshold sensitivities from SVOP. Overall, SVOP provided a similar shaped hill of vision as SAP however threshold sensitivities were higher, meaning results are not interchangeable.

Background: To examine the speed and accuracy of saccadic eye movements during a novel eye tracking threshold visual field assessment and determine whether eye movement parameters may improve ability to detect glaucoma., Methods: A prospective study including both eyes of 31 patients with glaucoma and 23 controls. Standard automated perimetry (SAP) and eye tracking perimetry (saccadic vector optokinetic perimetry, SVOP) was performed. SVOP provided data on threshold sensitivity, saccade latency, and two measures of accuracy of saccades (direction bias and amplitude bias). The relationship between eye movement parameters and severity of glaucoma was examined and Receiver Operating Characteristic curves were used to assess ability to detect glaucoma., Results: Patients with glaucoma had significantly slower saccades (602.9 ± 50.0 ms versus 578.3 ± 44.6 ms for controls, P = 0.009) and reduced saccade accuracy (direction bias = 7.4 ± 1.8 versus 6.5 ± 1.5 degrees, P = 0.006). There was a significant slowing of saccades and saccades became less accurate with worsening SAP sensitivity. Slower saccades were associated with increased odds of glaucoma; however, the AUC for saccade latency was only 0.635 compared to 0.914 for SVOP sensitivity., Conclusion: Patients with glaucoma had significant differences in eye movements compared to healthy subjects, with a relationship between slower and less accurate eye movements and worse glaucoma severity. However, in a multivariable model, eye movement parameters were not of additional benefit in differentiating eyes with glaucoma from healthy controls.

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: To determine the ability of Saccadic Vector Optokinetic Perimetry (SVOP) to detect and characterise visual field defects in children with brain tumours using eye-tracking technology, as current techniques for assessment of visual fields in young children can be subjective and lack useful detail., Methods: Case-series study of children receiving treatment and follow-up for brain tumours at the Royal Hospital for Sick Children in Edinburgh from April 2008 to August 2013. Patients underwent SVOP testing and the results were compared with clinically expected visual field patterns determined by a consensus panel after review of clinical findings, neuroimaging, and where possible other forms of visual field assessment., Results: Sixteen patients participated in this study (mean age of 7.2 years; range 2.9-15 years; 7 male, 9 female). Twelve children (75%) successfully performed SVOP testing. SVOP had a sensitivity of 100% and a specificity of 50% (positive predictive value of 80% and negative predictive value of 100%). In the true positive and true negative SVOP results, the characteristics of the SVOP plots showed agreement with the expected visual field. Six patients were able to perform both SVOP and Goldmann perimetry, these demonstrated similar visual fields in every case., Conclusion: SVOP is a highly sensitive test that may prove to be extremely useful for assessing the visual field in young children with brain tumours, as it is able to characterise the central 30° of visual field in greater detail than previously possible with older techniques.

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.

Aim: To explore the relationship between raised intracranial pressure (RICP) and retinal haemorrhages in traumatic and non-traumatic childhood encephalopathies., Method: A prospective study of 112 children (35 females and 77 males, age range 0.01mo-17y 8.3mo; mean 5y 8.6mo, median 4y 5.6mo) included 57 accidental traumatic brain injuries (ATBIs), 21 inflicted traumatic brain injuries (ITBIs), and 34 non-traumatic encephalopathy cases. Measurements included intracranial pressure (ICP), cerebral perfusion pressure, pressure-time index of ICP, and number, zone, and layer of retinal haemorrhages on retinal imaging., Results: Group I had measured elevated ICP (n=42), Group II had clinical and/or radiological signs of RICP (n=21), and Group III had normal ICP (n=49). In the combined Groups I and II, 38% had retinal haemorrhages. Multiple logistic regression confirmed that the presence of retinal haemorrhages was significantly related to the presence of RICP independent of age and aetiology; however, the occurrence and overall numbers were not significantly related to the specific ICP level. The numbers of intraretinal (nerve-fibre layer and dot blot) retinal haemorrhages were significantly greater in those with RICP. The ITBI population was significantly different from the other combined aetiological categories., Interpretation: The study results indicate a complex RICP/retinal haemorrhage relationship. There was no evidence of existing retinal haemorrhages being exacerbated or new retinal haemorrhages developing during periods of confirmed RICP., (© 2017 Mac Keith Press.)

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.

Background: There is currently no universally accepted classification of childhood retinal haemorrhages., Aim: To measure the inter- and intra-observer agreement of clinical classifications of retinal haemorrhages in children., Methods: Four examiners (two consultant ophthalmologists and two other clinicians) were shown 142 retinal haemorrhages on 31 RetCam photographs. The retinal haemorrhages were from children with accidental or abusive head injury, or other encephalopathies, and included retinal haemorrhages of different ages. Specified haemorrhages were initially classified by each examiner according to their clinical understanding. Altogether, 26 haemorrhages were re-presented to test intra-observer consistency. Examiners then agreed a common description for each haemorrhage type and five categories were described (vitreous, pre-retinal, nerve fibre layer, intra-retinal/sub-retinal or indeterminate) and the study repeated., Results: There was 'fair agreement' initially (Fleiss' unweighted κ=0.219) and, with the agreed classification, slight improvement (0.356). Intra-observer agreement marginally improved on re-test. The two consultant ophthalmologists showed 'fair' agreement on both occasions (paired κ statistic). The other rater pair improved from 'fair' to 'substantial' agreement with the new classification., Conclusions: The classification of retinal haemorrhage in children by appearance alone shows only fair agreement between examiners. Clinicians who are not consultant ophthalmologists appear to benefit from the new succinct classification.

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.

Objectives: Post-traumatic hypopituitarism is well described amongst adult traumatic brain injury (TBI) survivors. We aimed to determine the prevalence and clinical significance of pituitary dysfunction after head injury in childhood., Design: Retrospective exploratory study., Patients: 33 survivors of accidental head injury (27 boys). Mean (range) age at study was 13·4 years (5·4-21·7 years) and median (range) interval since injury 4·3 years (1·4-7·8 years). Functional outcome at study: 15 good recovery, 16 moderate disability, two severe disability., Measurements: Early morning urine osmolality and basal hormone evaluation were followed by the gonadotrophin releasing hormone (GnRH) and insulin tolerance (n = 25) or glucagon tests (if previous seizures, n = 8). Subjects were not primed. Head injury details were extracted from patient records., Results: No subject had short stature (mean height SD score +0·50, range -1·57 to +3·00). Suboptimal GH responses (<5 μg/l) occurred in six peri-pubertal boys (one with slow growth on follow-up) and one postpubertal adolescent (peak GH 3·2 μg/l). Median peak cortisol responses to insulin tolerance or glucagon tests were 538 and 562 nm. Nine of twenty-five and two of eight subjects had suboptimal responses, respectively, two with high basal cortisol levels. None required routine glucocorticoid replacement. In three, steroid cover was recommended for moderate/severe illness or injury. One boy was prolactin deficient. Other basal endocrine results and GnRH-stimulated LH and FSH were appropriate for age, sex and pubertal stage. Abnormal endocrine findings were unrelated to the severity or other characteristics of TBI or functional outcome., Conclusions: No clinically significant endocrinopathy was identified amongst survivors of accidental childhood TBI, although minor pituitary hormone abnormalities were observed., (© 2010 Blackwell Publishing Ltd.)

Background/aims: To develop and assess a zonal classification of the retina to facilitate description of the location of retinal haemorrhages in children., Methods: A novel zonal classification of the retina was devised based on the anatomical landmarks of the optic disc and vascular arcades, by reviewing a large number of wide field digital retinal images drawn from our database of children with accidental and non-accidental head injury and other encepthalopathies. Four expert examiners then independently 'located' 142 retinal haemorrhages by zone, from 31 high quality photographs., Results: Cohen's unweighted kappa scores for all possible pairs of the four raters (ie, six pairs) ranged from 0.86 to 0.92, that is 'almost perfect' agreement. Fleiss' kappa for agreement between multiple raters (four) and for multiple categories (three) was 0.8841, that is 'almost perfect' agreement. Cohen's unweighted kappa statistic for intrarater reliability gave an overall concordance that ranged from 'substantial' to 'perfect' agreement., Conclusion: This new retinal zone classification and the use of photographs and templates is a very reliable tool for reporting the location of retinal haemorrhages from multiple aetiologies in children, and may be useful for research and medico-legal reports.

Purpose: To determine the feasibility of a new technique for suprathreshold automated static perimetry in children., Design: Evaluation of diagnostic test or technology., Participants: The study included 29 subjects comprising 4 groups: 12 adults with normal fields, 4 children aged less than 10 years with normal fields, 8 adults with visual field defect, and 5 children aged less than 10 years with suspected visual field defects., Methods: The system comprises a personal computer, display, and eye tracker to monitor gaze position when stimuli are presented in the visual field. The natural saccadic eye movement to fixate on the stimuli, if seen, can be detected and measured to produce a visual field plot. Subjects performed 3 eye-tracking tests, unless unable to do so for any reason: a 40-point binocular test and two 41-point tests for each eye. The tests were based on the Humphrey Field Analyzer (HFA) Central-40 point screening test with a stimulus size of Goldmann III and intensity of 14 decibels (dB). Adults also performed the equivalent Humphrey screening test in each eye for comparison., Main Outcome Measures: Comparison of visual field plot results between the eye-tracking tests and HFA tests in adults. Correlation between the eye-tracking tests and the clinical assessment in the children with suspected visual field defects., Results: In the eyes of all normal adult and child subjects performing the eye-tracking test, the percentage of points in agreement with a healthy visual field was 99.2% and 99.1%, respectively. The percentage of points agreeing with the HFA's screening test in the adult eyes with visual field defects was 89.8%. Visual field defects were also correctly identified by the eye-tracking system in the eyes of children with suspected visual field defects., Conclusions: The results demonstrate that suprathreshold automated static perimetry using eye tracking is a promising method of perimetry for use with children.

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.

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.

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.

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: +/-25.73); and mean mental development index, 74.53 (SD: +/-28.55). Adaptive functioning showed a wide range of difficulties across all domains: communication domain (mean: 76.1; SD: +/-25.4), Daily living skills domain (mean: 76.9; SD: +/-24.3), and socialization domain (mean: 79.1; SD: +/-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.

Interstitial deletions of the middle portion of the long arm of chromosome 5 are relatively rare. So far, only 36 cases have been reported. Because of the repetitive banding pattern of this region, the extent and localization of the deleted segment has not been well characterized in the majority of reported cases. This has complicated attempts to establish a definite karyotype-phenotype correlation. We report a further case with a de novo interstitial deletion of the region 5q?15 to 5q?22 identified by standard karyotype analysis. The proband presented with failure to thrive, developmental delay, distinct craniofacial dysmorphic features, and associated structural anomalies (amongst them cleft palate, iris colobomata, and horseshoe kidney, which have previously been reported in 5q deletion cases). In addition, this child had an Arnold-Chiari type I malformation that required surgical decompression. FISH studies using BAC clones spanning the 5q15 to 5q22 region revealed that these were all present in both homologues. Use of more distal clones allowed delineation of the deleted region to 5q22.3q23.3 and to narrow down the breakpoints to approximately 200 kb. The 14 Mb deleted region contains about 60 genes but, with the possible exception of FBN2 and DMXL1, there are no obvious candidate genes for the specific components of the phenotype. This case illustrates the discrepancy between cytogenetic and molecular techniques in trying to delineate 5q interstitial deletions. Molecular studies need to be performed on these patients, to establish genotype-phenotype correlation and to understand the role and influence of genes in this region., ((c) 2005 Wiley-Liss, Inc.)

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.

Purpose: 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., Methods: A cross-sectional and prospective study of children admitted to hospital with NAHI in Scotland., Results: 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., Conclusions: 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.