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Both detrimental and beneficial effects of post-traumatic neuroinflammation have become a major research focus as they offer the potential for immediate as well as delayed targeted reparative therapies. Understanding the complex interactions of central and peripheral immunocompetent cells as well as their mediators on brain injury and recovery is complicated by the temporal, regional, and developmental differences in their response to injuries. Microglia, the brain-resident macrophages, have become central in these investigations as they serve a major surveillance function, have the ability to react swiftly to injury, recruit various cellular and chemical mediators, and monitor the reparative/degenerative processes. In this review we describe selected aspects of this burgeoning literature, describing the critical role of cytokines and chemokines, microglia, advances in neuroimaging, genetics and fractal morphology analysis, our research efforts in this area, and selected aspects of pediatric post-traumatic neuroinflammation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Practice guidelines have been developed in child neurology during the last fifteen years to address important clinical questions and provide evidence-based recommendations for patient care., Methods: This review describes the guideline development process and how it has evolved to meet the needs of child neurologists., Results: Several current child neurology guidelines are reviewed and the advantages and disadvantages of guidelines, as well as the legal consequences of using them to determine a standard of care are discussed. The future of guidelines and of their influence on integrated support systems also is considered., Conclusions: Child neurology practice guidelines are a helpful resource for clinicians, families and institutions as they provide evidence-based recommendations concerning the diagnosis and management of common neurological conditions affecting children. Incorporating consensus processes has allowed expansion of clinically relevant recommendations that has increased the utility of guidelines., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Evaluation of acute ataxia in a child poses a dilemma for the clinician in determining the extent and timing of initial screening tests. This article reviews the evidence concerning the diagnostic yield of commonly ordered tests in evaluating the child with acute ataxia. The literature revealed the following frequencies of laboratory screening abnormalities in children with acute ataxia: CT (∼2.5%), MRI (∼5%), lumbar puncture (43%), EEG (42%), and toxicology (49%). In most studies, abnormalities detected by these screening tests were nondiagnostic. There are insufficient data to assess yields of testing for autoimmune disorders or inborn errors of metabolism. A toxicology screen should be considered in all children presenting with acute ataxia. Neuroimaging should be considered in all children with new onset ataxia. Cerebrospinal fluid analysis has limited diagnostic specificity unless clinically indicated. Studies to examine neurophysiology testing did have sufficient evidence to support their use. There is insufficient evidence to establish a role for autoantibody testing or for routine screening for inborn error of metabolism in children presenting with acute ataxia. Finally, in a child presenting with ataxia and opsoclonus myoclonus, urine catecholamine testing for occult neuroblastoma is recommended. Nuclear scan may be considered, however, there is insufficient evidence for additional body imaging., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Magnetic resonance imaging is increasingly used to assess neonatal hypoxic-ischemic injury, and several scoring systems were developed to predict neurologic outcomes in these patients. We examined the magnetic resonance imaging studies of 33 neonates/infants who manifested acute perinatal hypoxic-ischemic injuries. Using a seven-point susceptibility-weighted imaging categorical grading scale, each patient received a "prominence of vein" score, which was dichotomized into a "normal" or "abnormal" group. Six-month outcomes were assessed using the Pediatric Cerebral Performance Category Scale. We then determined whether "prominence of vein" scores correlated with neurologic outcomes in patients with hypoxic-ischemic injuries, and compared these results with the Barkovich magnetic resonance imaging scoring system. Patients with "normal" "prominence of vein" scores demonstrated better outcomes (mean Pediatric Cerebral Performance Category Scale value = 2) than patients with "abnormal" "prominence of vein" scores (mean Pediatric Cerebral Performance Category Scale value = 4). The dichotomized "prominence of vein" groups demonstrated correlations with the Barkovich magnetic resonance imaging scores of the proton density-weighted basal ganglia, watershed, and combined basal ganglia/watershed regions. The susceptibility-weighted imaging categorical grading scale may aid in predicting neurologic outcomes after hypoxic-ischemic injuries., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We investigated whether morphine plays a neuroprotective role in a neonatal rat pup model of bilateral carotid artery occlusion with hypoxia. At postnatal day 10, rats received either morphine (n = 7), naloxone (n = 7), or saline placebo (n = 15) after hypoxic-ischemic injury. Survival (days), weight gain and animal testing (negative geotaxis, surface righting, and rotarod) were compared between treatment groups. Lesion volume was delineated with magnetic resonance imaging at days 7 and 28-57 after injury. Survival in rats treated with morphine, naloxone, or saline was, respectively, 14, 29, and 73%. Median number of days of survival after bilateral carotid artery occlusion with hypoxia treated with morphine was 4 (95% confidence interval 4 to 22), with naloxone was 3 (95% confidence interval -1.4 to 21), and with placebo was 28 (95% confidence interval 18 to 28). There were no statistically significant differences in magnetic resonance imaging-derived ischemic lesion volumes, weight gain, or behavioral testing measures between the groups. Morphine was ineffective as a neuroprotectant in rat pups with severe hypoxic-ischemic injury and may have contributed to their decreased survival., (Published by Elsevier Inc.)

Apparent diffusion coefficient maps from diffusion-weighted imaging predict gross neurologic outcome in adults with traumatic brain injury. Few studies in children have been reported, and none have used apparent diffusion coefficient maps to predict long-term (>1 year) neurocognitive outcomes. In this study, pooled regional and total brain diffusion coefficients were used to predict long-term outcomes in 17 pediatric brain injury patients. Apparent diffusion coefficient values were grouped into peripheral and deep gray and white matter, posterior fossa, and total brain. Regions of interest excluded areas that appeared abnormal on T(2)-weighted images. Apparent diffusion coefficient values from peripheral regions were inversely correlated with cognitive functioning. No significant correlations were apparent between the cognitive scores and apparent diffusion coefficient values for deep tissue or the posterior fossa. Regression analyses suggested that combined peripheral gray and white matter apparent diffusion coefficients explained 42% of the variance in the combined neurocognitive index. Peripheral gray diffusion coefficients alone explained an additional 20% of variance after accounting for clinical variables. These results suggest that obtaining apparent diffusion coefficient values, specifically from peripheral brain regions, may predict long-term outcome after pediatric brain injury. Discrepancies in the literature on this topic, as well as possible explanations, including sampling and clinical considerations, are discussed.

Diffusion-weighted imaging and its quantitative apparent diffusion coefficient can assess severity in newborn hypoxic-ischemic injuries. A meta-analysis established normative values in term newborns, in comparison to those values in hypoxic-ischemic newborns with good versus poor outcomes. Measurements from 14 reports were stratified into three levels of increasing specificity: tissue type (gray matter, white matter, or cerebellum), tissue distribution (e.g., cortex or white-matter tracts), and anatomic structures (e.g., frontal white matter or posterior limb of the internal capsule). Normative apparent diffusion coefficients constituted white matter > gray matter = cerebellum, with lowest values in the posterior limb of the internal capsule and thalamus, and the highest in frontal and occipital white matter. Differences between normative and hypoxic-ischemic injury good-outcome groups were not evident. Values in the poor outcome group were significantly lower than normative data in white matter, gray matter, cortical gray matter, white matter tracts, posterior limb of the internal capsule, and cortical, frontal, and occipital white matter. Comparisons between injury groups found that coefficients were only significantly lower in the occipital cortex among poor outcomes. Coefficient values were lower in deep brain compared with cortical structures, reflecting tissue maturation and myelination. Differences between normative and hypoxic-ischemic injury poor-outcome groups suggest pathologies associated with neurologic sequelae. This meta-analysis provides the basis for normative apparent diffusion coefficient values in the newborn brain.

Neonatal global or focal hypoxic-ischemic brain injury remains a frequent and devastating condition, with serious long-term sequelae. An important issue in any neonatal clinical trial of neuroprotective agents relates to developing accurate measures of injury severity and also suitable measures of the response to treatment. Advanced magnetic resonance imaging techniques can acquire serial and noninvasive data about brain structure, metabolic activity, and the response to injury or treatment. These imaging methods need validation in appropriate animal models for translational research studies in human newborns. This review describes several approaches that use imaging as well as proton magnetic resonance spectroscopy to assess the severity of ischemic injury (e.g., for possible candidate selection) and for monitoring the progression and evolution of injury over time and as an indicator of recovery or response to treatment. Preliminary data are presented on how imaging can be used after neural stem cell implantation to characterize the migration rate, the magnitude of stem cell proliferation, and their final location. Imaging has the potential to allow monitoring of many dimensions of neuroprotective treatments and can be expected to contribute to efficacy and safety when clinical trials using neural stem cells or other neuroprotective agents become available.

Animal models are often presumably the first step in determining mechanisms underlying disease, and the approach and effectiveness of therapeutic interventions. Perinatal brain damage, however, evolves over months of gestation, during the rapid maturation of the fetal and newborn brain. Despite marked advances in our understanding of these processes and technologic advances providing an improved window on the timing and duration of injury, neonatal brain injury remains a "moving target" regarding our ability to "mimic" its processes in an animal model. Moreover, interfering with normal processes of development as part of a therapeutic intervention may do "more harm than good." Hence, controversy continues over which animal model can reflect human disease states. Numerous models have provided information regarding the pathophysiology of brain damage in term and preterm infants. Our challenges consist of identifying infants at greatest risk for permanent injury, identifying the timing of injury, and adapting therapies that provide more benefit than harm. A combination of appropriately suitable animal models to conduct these studies will bring us closer to understanding human perinatal damage and the means to treat it.

Traumatic brain injury is a common cause of death and disability in children; early neuroimaging has assumed an increasingly important role in evaluating the extent and severity of injury. Several imaging methods were assessed in a study of 40 children with traumatic brain injury: computed tomography (CT), T(2)-weighted magnetic resonance imaging (MRI), fluid-attenuated inversion recovery (FLAIR) MRI, and susceptibility-weighted imaging (SWI) MRI to determine which were most valuable in predicting 6-12 month outcomes as classified by the Pediatric Cerebral Performance Category Scale score. Patients were subdivided into three groups: (1) normal, (2) mild disability, and (3) moderate/severe disability/persistent vegetative state. T(2), FLAIR, and SWI showed no significant difference in lesion volume between normal and mild outcome groups, but did indicate significant differences between normal and poor and between mild and poor outcome groups. Computed tomography revealed no significant differences in lesion volume between any groups. The findings suggest that T(2), FLAIR, and SWI MRI sequences provide a more accurate assessment of injury severity and detection of outcome-influencing lesions than does CT in pediatric traumatic brain injury patients. Although CT was inconsistent at lesion detection/outcome prediction, it remains an essential part of the acute traumatic brain injury work-up to assess the need for neurosurgic intervention.

At Loma Linda University Children's Hospital, the medical information of 405 pediatric patients who received orthotopic cardiac transplantation were reviewed. Of those who died (n=136), 86% (n=117) underwent postmortem examinations, and the brain was examined in 61% (n=82, male=39). The number and type of intracranial lesions present were compiled, and these were matched to underlying functional cardiac disease categories. Intracranial abnormalities were present in 87%. Infarct was the most common primary central nervous system pathology in hypoplastic left heart syndrome (41%) but was also observed frequently in children with obstructive lesions (37%), cyanotic disease (31%), or cardiac shunting (29%). Secondary findings included extraparenchymal hemorrhage in obstructive lesions (31%); hypoxic changes occurred in 15% of patients with cyanotic disease and in 14% of those with cardiac shunting. Thirty-three percent of children with restrictive lesions had no neuropathology reported. Postmortem examination brain weights were matched against age and sex norms, with 29% of females and 36% of males below two standard deviations. These findings revealed that intracranial pathology was present in the majority of transplanted children who underwent postmortem examination, and that infarctive changes constituted the most common neuropathologic abnormality. Additionally, a number of children had significantly reduced brain weight.

Preclinical animal models can help guide the development of clinical pediatric and newborn stroke trials. Data obtained using currently available models of hypoxia-ischemia and focal stroke have demonstrated the need for age-appropriate models. There are age-related differences in susceptibility of the immature brain to oxidative stress and inflammation, as well as in the rate and degree of apoptotic neuronal death. These issues need to be carefully addressed in designing future clinical trials.

Traumatic brain injury is among the most frequent pediatric neurologic disorders in the United States, affecting multiple aspects of neuropsychologic functioning. This study assessed the efficacy of susceptibility weighted imaging as a predictor of long-term neuropsychologic functioning after pediatric brain injury compared with magnetic resonance spectroscopic imaging. Susceptibility weighted imaging is a relatively new method that is considered superior to traditional magnetic resonance imaging sequences for detecting hemorrhagic diffuse axonal injury. In this study, imaging and spectroscopy were acquired 6 +/- 4 days after injury. Measures of neuropsychologic functioning were administered to 18 children and adolescents 1-4 years post injury. Negative correlations between lesion number and volume with neuropsychologic functioning were demonstrated. Lesion volume explained over 32% of the variance in cognitive performance, explaining at least an additional 20% beyond injury severity and age at injury alone and 19% beyond magnetic resonance spectroscopic metabolite variables. Exploratory analyses resulted in notable trends, with lesions in deeper brain regions more strongly associated with poorer neuropsychologic performance. Improved detection of the extent of diffuse axonal injury following a brain injury will allow for a better understanding of its association with long-term outcome, which in turn can improve prognostic efficacy for effective treatment planning.

We used proton magnetic resonance spectroscopy to study 11 children (age < 8 years) with congenital heart disease undergoing cardiopulmonary bypass to determine whether low (10 +/- 4; n = 6) vs high (20 +/- 4; n = 5) perfusate hematocrits during bypass resulted in changes in brain metabolites which correlate with neurologic injury. Long and short echo time single voxel magnetic resonance spectroscopy in occipital gray matter and neurologic assessment were performed preoperatively and 2 and 5 days postoperatively. We also determined whether prolonged periods at low flow rates during bypass affected spectroscopy variables. We found no significant differences in metabolite ratios between the low vs high hematocrit groups or the lower vs higher flow rate groups (repeated measures analysis of variance of observation ranks converted to normal scores). However, our study was limited by statistical power due to the small sample size, therefore no conclusions could be made. Additional studies involving a greater number of patients are necessary. In all 11 children, magnetic resonance spectroscopy detected a significant decrease in brain N-acetyl-aspartate, and increases in myoinositol and glutamate/glutamine after surgery (Quade test) demonstrating that magnetic resonance spectroscopy is sensitive in detecting subtle postoperative changes in brain metabolites.

Seizures are common in infants undergoing cardiac transplant and are usually attributed to a non-specific "post-pump" phenomenon. In this study, we determined which variables were associated with the occurrence of post-transplant seizures in infants with hypoplastic left heart syndrome and the need for continued treatment with antiepileptic medication. Of 127 infants studied over an 11-year period, 27 (21%), ages 9 to 90 days, had post-transplant seizures. These patients were compared to 27 age-matched transplanted infants without seizures. We compared multiple variables before, during, and after transplant including growth parameters, time of diagnosis, cyclosporine levels, maternal variables, circulatory and bypass parameters, laboratory data, neuroimaging and electroencephalographic studies, neurologic examination findings, and peri-operative complications. Post-transplant seizures were associated with total cardiopulmonary bypass time and the presence of post-transplant complications. Deep hypothermic circulatory arrest time was inversely correlated with seizure severity. Pre-transplant electroencephalographic abnormalities and total bypass time were associated with seizures requiring continued use of antiepileptic therapy. Post-transplant electroencephalograms were not associated with the need for continued treatment. Identification of variables associated with the development of post-transplant seizures is essential for early intervention to reduce long-term morbidity and mortality. Future studies to reduce risk of post-transplant seizures are warranted.

The ability to predict long-term neurologic and neuropsychologic outcomes in 22 children, ages 1 week to 14 years at the time of traumatic brain injury, was investigated using proton magnetic resonance spectroscopy acquired post injury and compared with standardized neurologic, intellectual, and neuropsychologic testing done 1-7 years later. Clinical indicators of acute injury severity including age at injury, electroencephalography, spectroscopy metabolite ratio variables (N-acetyl aspartate/choline, choline/creatine) and lactate presence accurately classified children as functioning above or below the average range for most intellectual and neuropsychologic outcome measures. Combined clinical and spectroscopy variables accounted for approximately 50% of the variance in cognitive and neuropsychologic outcome confirming the validity of their predictive use. Of the injury severity indictors, presence of lactate is a particularly important prognostic marker of poor long-term intellectual and neuropsychologic functioning. Our findings indicate the potential for providing accurate estimates of long-term intellectual and neuropsychologic function after traumatic brain injury in infants and children using proton magnetic resonance spectroscopy in combination with clinical variables.

We determined estimates of survival in children, 3-15 years of age, in the vegetative state (VS) (n = 564), immobile minimally conscious state (MCS) (n = 705), and mobile MCS (n = 3,806). Data were extracted from the annual Client Development Evaluation Reports of the California Department of Developmental Services between 1988 and 1997 using the operational definitions for these three states on the basis of 15 descriptive behavioral categories. Patients were also categorized according to the following four etiologies: acquired (traumatic and nontraumatic) brain injury; perinatal/genetic; degenerative; and unknown/undetermined. The percentage of patients surviving 8 years was 63%, 65%, and 81%, for the VS, immobile MCS, and mobile MCS, respectively. Children in the VS and MCSs with acquired brain injury had lower mortality rates and those with degenerative diseases the highest mortality rates. We observed little difference in survival between patients in the VS and immobile MCS, suggesting that the presence of consciousness is not a critical variable in determining life expectancy. Furthermore, survival was much greater for patients in the mobile MCS than for those in the immobile MCS, suggesting that mobility is more important in predicting survival than the level of consciousness.

We studied 26 infants (1-18 months old) and 27 children (18 months or older) with acute nonaccidental (n = 21) or other forms (n = 32) of traumatic brain injury using clinical rating scales, a 15-point MRI scoring system, and occipital gray matter short-echo proton MRS. We compared the differences between the acutely determined variables (metabolite ratios and the presence of lactate) and 6- to 12-month outcomes. The metabolite ratios were abnormal (lower NAA/Cre or NAA/Cho; higher Cho/Cre) in patients with a poor outcome. Lactate was evident in 91% of infants and 80% of children with poor outcomes; none of the patients with a good outcome had lactate. At best, the clinical variables alone predicted the outcome in 77% of infants and 86% of children, and lactate alone predicted the outcome in 96% of infants and 96% of children. No further improvement in outcome prediction was observed when the lactate variable was combined with MRI ratios or clinical variables. The findings of spectral sampling in areas of brain not directly injured reflected the effects of global metabolic changes. Proton MRS provides objective data early after traumatic brain injury that can improve the ability to predict long-term neurologic outcome.

The authors studied life expectancy and risk factors for mortality of persons in the vegetative state (VS). The study participants were 1,021 California patients in the VS during 1981-1996. Because of the large sample size, the authors were able to use multivariate methods to assess the effect of several risk factors on mortality. The authors found a strong secular trend in infant mortality, with rates in the mid-1990s being only one third of those in the early 1980s (P < 0.01). A smaller secular trend was observed for children aged 2-10 years and none for older patients. The mortality risk for older patients fell by approximately 8% for each year since the onset of the VS. The need for gastrostomy feeding was associated with a substantially higher risk, especially for infants and older patients (P < 0.01). Ventilator dependence also appeared to be a risk factor. On the basis of recent mortality rates, life expectancy in the VS is frequently higher than has generally been thought. For example, it is 10.5 additional years (+/- 2 years) for a 15-year-old patient who has been in the VS for 1 year, and 12.2 years for a 15-year-old patient who has been in the VS for 4 years.

The authors studied 37 term neonates (38-42 gestational weeks) at 1-11 days after central nervous system insult to determine whether proton magnetic resonance spectroscopy (1H-MRS) of the occipital gray/parietal white matter was useful in predicting outcomes. Etiologies included asphyxia, 18; sepsis/meningitis, 8; metabolic disorders, 5; stroke, 4; and trauma, 2. 1H-MRS data (1.5T; 8 cm3 vol, stimulated echo acquisition mode sequence, TE = 20 ms, TR = 3000 ms) were expressed as metabolite peak area ratios (NAA/Cr, NAA/Cho, Cho/Cr) and the presence or absence of lactate. Outcomes were assessed at 6 to 12 months post-insult using the Pediatric Cerebral Performance Scale and were dichotomized as follows: good/moderate outcome (good, mild or moderate disability) or poor outcome (severe disability, persistent vegetative state, death). Neonates with poor outcomes had significantly lower NAA/Cho and significantly higher Cho/Cr ratios in the occipital region, as compared with patients with good/moderate outcomes. No neonates with good/moderate outcomes had metabolite ratios that exceeded 2 standard deviations from the mean. In addition, the absence of lactate on 1H-MRS correlated with a good/moderate outcome. The study also showed that 1H-MRS metabolite ratio data, added to either the Sarnat or EEG scores, enhanced the correlation between these prognostic factors and outcomes. 1H-MRS provides additional objective data early after a wide variety of perinatal neurologic insults to enhance outcome prediction.

A 17-year-old Russian male with a 9-year diagnosed history of dystonia musculorum deformans manifested as severe tortipelvis, lordosis, and axial and appendicular spastic dystonia, refractory to medical therapy, is reported. This patient underwent a simultaneous bilateral pallidoansotomy with dramatic results. Postoperative evaluation revealed sustained alleviation of all dystonic symptoms and abnormal movements. Rapid recovery of useful strength in all limbs as well as dramatic improvement in coordination occurred. Bilateral posteroventral pallidotomy and pallidoansotomy in the past have proven effective in alleviation of all parkinsonian symptoms, including dyskinesia and dystonia, without the concurrent risk of intransigent side effects associated with bilateral thalamotomy or other stereotactic surgical procedures. Pallidoansotomy may prove to be the treatment of choice for idiopathic torsion dystonia and merits further investigation.

Single voxel proton magnetic resonance spectroscopy (1H-MRS) was used in 30 infants and children with acute central nervous system injuries to determine the value of changes in specific metabolite ratios in predicting outcome. The mean age of all patients was 38 +/- 52 months and the mean time of study after insult was 7 +/- 5 days. 1H-MRS was determined in the occipital gray and parietal white matter (8 cm3 volume, STEAM sequence with TE = 20 ms, TR = 3,000 ms). Data were expressed as ratios of different metabolite peak areas including N-acetylaspartate (NA), choline-containing compounds (Ch), creatine and phosphocreatine (Cr), and lactate (Lac). Statistically significant differences were observed when patients with good/moderate (G/M) outcomes (n = 17; mean age: 46 months) were compared to patients with bad outcomes (n = 10; mean age: 26 months). NA/Cr and NA/Ch were significantly lower in the bad outcome group (NA/Cr = 1.15 +/- 0.38; NA/Ch = 1.18 +/- 0.52) compared to the G/M group (NA/Cr = 1.41 +/- 0.28, P < .05; NA/Ch = 1.98 +/- 0.81, P < .01). Lactate was present in 80% of bad outcome patients and in none of the G/M group (P < .0001). Using a linear discriminant analysis and combining 4 clinical variables (Glasgow Coma Scale score, initial pH and glucose, number of days unconscious at time of 1H-MRS) allows classification of 94% of patients into their correct outcome group. Use of spectroscopy variables (NA/Cr, NA/Ch, Ch/Cr, presence of lactate) alone correctly classified 81% of patients. The combination of clinical and 1H-MRS variables correctly classified 100% of patients. Our findings suggest that 1H-MRS adds information which, in combination with clinical examination, may be useful in outcome assessment in children with serious acute central nervous system injury.

Neonatal stroke remains a complex pathophysiologic process that is poorly understood and difficult to investigate. The primary animal model used to study this phenomenon is that of unilateral carotid artery ligation with 2-3 hours exposure to severe hypoxia. A new model of neonatal stroke was developed based on transient middle cerebral artery occlusion without craniectomy. In this model a #6-0 (0.07 mm) nylon filament is passed via the carotid artery to occlude reversibly the middle cerebral artery for 4 hours under conditions of normoxia in 14- to 18-day-old spontaneously hypertensive rat pups. After removal of the filament and reperfusion for 24 hours, the infarct volume was determined using the mitochondrial stain, 2,3,5-triphenyltetrazolium chloride. Using this technique, a neocortical and caudoputamenal infarct affecting 49% of hemispheric volume that measured 180 +/- 29 mm3 (hemisphere volume = 359 +/- 16 mm3, mean +/- SEM) was created in 90% of animals (n = 8) undergoing this procedure. This model has the advantage of being relatively noninvasive, of not requiring global exposure of brain to hypoxia, and of using temporary rather than permanent occlusion. This technique should improve the ability to study the acute and long-term pathophysiology of neonatal stroke, particularly the phenomenon of reperfusion injury, as well as its sequelae in the developing nervous system.

The persistent vegetative state (PVS) is a state of wakeful unconsciousness occurring in adults and children. Despite preservation of vegetative functions, PVS patients have a shortened life-span, although accurate information concerning this issue remains limited. The survival of children in PVS was examined to determine whether age, etiology of the vegetative state, or type of residence in which the patient lived affected the estimated survival. The data of 155,851 developmentally disabled California state residents were reviewed using the Client Development Evaluation Report (CDER). Criteria from the CDER were selected to define the vegetative state and included: lack of interaction with peers; absence of auditory, visual, and expressive or receptive language function; no hand or arm use; inability to eat, sit, roll over, or lift head; and no bowel or bladder control. There were 847 patients who met these criteria on the initial and follow-up CDERs. A product limit survival model was used to develop survival curves and to calculate the median survival time for patients grouped by age, etiology, and type of residence. Median survival (yrs) for patients who remained in PVS for the following age groups was: < 1 yr: 2.6, 1 < 2 yrs: 4.2, 2-6 yrs: 5.2, 7-18 yrs: 7.0, > or = 19 yrs: 9.9. Median survival based on etiology varied from 3.0 to 8.6 years; no consistent relationship existed between etiology and duration of survival. Survival (yrs) for patients younger than age 18 years based on type of residence included: own home: 4.5, institutions: 5.2, skilled nursing facility/private hospital: 3.2, and other community care facilities: 3.7.(ABSTRACT TRUNCATED AT 250 WORDS)

End of life care for patients with Duchenne muscular dystrophy (DMD) has become increasingly complex because of new technologies, changes in medical personnel over periods of time, emergence of home health care systems, and increasing patient and family autonomy in decision-making. In this review, we discuss the medical problems, particularly respiratory and cardiac failure, faced by DMD patients. Current concepts concerning the evaluation and options for treatment of these problems are presented as well as the ethical issues involved in the care of the DMD patient. These issues include the medical indications for treatment, patient preferences, quality-of-life issues, and contextual features related to legal, institutional, religious, geographic, cultural, social, and financial factors. We also present our experience at Loma Linda University Medical Center over the past 10 years in the development of a home mechanical ventilation program for DMD patients and an algorithm for the evaluation of these patients. Many patients with DMD do well on long-term ventilation, but some find that their quality of life is less than desirable and choose to discontinue this method of life-prolongation. Many of these new options are very expensive, making the decision to use them a difficult one. Ultimately, these are societal issues that require clear reflection on matters of resource allocation that should be performed by health care professionals, citizens, and health planners.

Eight children with Guillain-Barré syndrome were treated with plasmapheresis. Retrospective comparisons were made with 11 historic control patients. Eight children required mechanical ventilation, 4 of whom were in the plasmapheresis group. One week after the last plasmapheresis treatment, patients receiving plasmapheresis within 7 days of symptom onset had improved by one Guillain-Barré syndrome score. Discharge Guillain-Barré syndrome scores were significantly lower for those receiving plasmapheresis (P < .05). Patients in the plasmapheresis group had a decrease in the number of days of mechanical ventilation, time until motor recovery, and overall cost. Our results are consistent with published literature and indicate that plasmapheresis for childhood Guillain-Barré syndrome is a safe and effective treatment to shorten the time to recovery.

Four children with self-inflicted strangulation injuries had cerebral blood flow determined by stable xenon computed tomography (XeCTCBF) within 24 hours of admission. All had suffered a severe hypoxic-ischemic cerebral injury; 3 initially had fixed pupils, all were apneic with varying bradyarrhythmias, and the initial mean arterial pH was 7.26 (+/- 0.18). The initial blood glucose values were greater than 300 mg/dl (334 and 351 mg/dl) in the 2 patients who died compared to the 2 who survived (104 and 295 mg/dl). The cardiac index was depressed during the first several days of hospitalization in the 2 patients who died (less than 2.0 L/min/m2) compared to the 2 who survived. Total CBF was normal (63 +/- 8 ml/min/100 gm) and local variations in CBF were present. PCO2 reactivity was determined by hyperventilating the 4 patients for 20 min from an end tidal PCO2 of 39 +/- 3 torr to 29 +/- 1 torr and then repeating the XeCTCBF study. Marked regional variability in the CBF/PCO2 response was observed, ranging from 0.5-5.5 ml/min/100 gm/torr PCO2. In the 2 patients who died, the CBF/PCO2 was decreased (1.2 ml/min/100 gm/torr PCO2) compared to the 2 patients who survived (2.1 ml/min/100 gm/torr PCO2). Although CBF was normal in these 4 children, the hyperventilation response was depressed, variable, and even paradoxical which may be important in the evolution of further brain injury and is a critical factor in deciding whether hyperventilation may be of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function, including loss of all cranial nerve responses and sustained apnea (PCO2 greater than 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12), suck, root, and gag responses (7), increased tone (8), deep tendon reflexes (9), absent pupillary responses (9), absent oculocephalic and corneal responses (6), absent auditory/Moro responses (7), and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently, the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that, although rare, clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation.

Infantile myositis is an inflammatory myopathy occurring in children under one year of age. This condition is extremely rare in the neonatal period and may be confused with other causes of generalized weakness. Creatine kinase activity is usually markedly elevated and electromyography demonstrates low amplitude, polyphasic motor unit activity. Muscle biopsy, necessary for diagnosis, documents characteristic findings of perifascicular atrophy and the presence of perivascular inflammatory cells. The diagnosis should be followed by corticosteroid treatment. The patient presented is the youngest biopsy-proved case of infantile myositis. In this report, his symptoms and clinical course are compared with those of previously described patients. The role of infectious agents and the immune state in the etiology of infantile myositis is considered.

We report 3 children with reflex sympathetic dystrophy syndrome, review the literature, and discuss current concepts of diagnosis and management. In this disorder, pain, tenderness, swelling, vasomotor instability, and dystrophic skin changes frequently develop after minor injury. The clinical diagnosis is supported by osteopenia detected on radiographs and either increased or decreased radionuclide uptake on bone scan of the affected extremity. Treatment with a graduated program of physical therapy and transcutaneous electrical nerve stimulation is beneficial in almost all patients. In contrast to adults, the prognosis of childhood reflex sympathetic dystrophy syndrome is favorable; most children recover completely after one episode.

The determination of brain death during childhood has become increasingly important and in some ways controversial. This initial article reviews historical data and guidelines and provides a perspective for the recommendations which will be discussed in the second article (Part II).

The determination of brain death in children has increasingly relied on a variety of neurodiagnostic studies to confirm the clinical diagnosis. This second article on brain death reviews the relevant pediatric electroencephalographic, evoked response, and cerebral blood flow studies, provides our recommendations and protocol for the determination of brain death in children, and considers some of the problems associated with physiologic stabilization of the brain dead child who is considered for organ donation.

Myoadenylate deaminase (MADA) is an enzyme which participates in the purine nucleotide cycle necessary for energy production in human skeletal muscle. Approximately 35 patients with deficiency of this enzyme have been reported; one-half experienced their initial difficulties in childhood. Children with "primary" MADA deficiency typically have symptoms including muscle cramps, stiffness, and post-exercise myalgia and weakness. In "secondary" MADA deficiency, the clinical findings have been variable with delayed motor development, hypotonia, cardiomyopathy, delayed speech development, and generalized weakness. In most cases creatine kinase determinations, nerve conduction velocity studies, and routine muscle histopathology have been normal. Diagnosis has been established by demonstrating an absence of MADA activity by either direct muscle enzyme assay or histochemical staining. In this report we describe a 12-year-old boy with primary MADA deficiency and contrast his symptoms with those of previously described pediatric patients.