Prediction of outcome after hypoxic-ischemic encephalopathy: a prospective clinical and electrophysiologic study

OBJECTIVES: To evaluate and compare the predictive value of history, clinical examination, and biologic and electrophysiologic data regarding the prognosis of children with acute hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Prospective cohort of 57 consecutive children who were mechanically ventilated for HIE throughout a 3-year period in a tertiary pediatric intensive care unit at a university hospital in France. RESULTS: At 24 hours after admission, 12 patients had died, 3 were awake and 42 showed impaired consciousness or were in a coma, of whom 38% had a favorable outcome. In this group, an initial cardiopulmonary resuscitation duration longer than 10 minutes and a Glasgow Coma Scale <5 at 24 hours after admission were associated with an unfavorable outcome (positive predictive value [PPV] 91%, 100%; sensitivity 50%, 54%). A discontinuous electroencephalogram (EEG), the presence of spikes or epileptiform discharges were associated with an unfavorable outcome (PPV 100% for the 2 criteria; sensitivity 27%, 54%). The bilateral absence of the N20 wave on short-latency sensory evoked potentials (SEPs) had a PPV for unfavorable outcome of 100% (sensitivity 63%). CONCLUSIONS: The clinical assessment combined with EEG and SEPs allow an early prediction of the prognosis of children with HIE.     

Computed tomography in bacterial meningitis of childhood

The hospital records of 85 children with bacterial meningitis were reviewed and a subset of 25 children who underwent computed tomography of the head were identified. The major stated indications for computed tomography were fever (8 patients), seizures (4 patients), signs of increased intracranial pressure (4 patients), focal neurologic dysfunction (3 patients) and recurrent meningitis (2 patients). Abnormal findings were demonstrated by computed tomography in 20 of 25 patients but in 8 patients consisted solely of nonspecific dilatation of spaces containing cerebrospinal fluid or of basilar enhancement. The yield of information that was useful either diagnostically or therapeutically was low; positive findings of obvious clinical relevance were present in only 2 cases. Computed tomography provides an accurate means of diagnosing intracranial complications of bacterial meningitis. It must be used conservatively, however, to limit expense and radiation exposure and enhance the yield of potentially relevant information. Computed tomography is indicated for children with persistent neurologic dysfunction, persistently positive cerebrospinal fluid cultures or recurrent meningitis, whereas it is of little value for children with prolonged fever alone.     

Mastoiditis in children: a prospective, observational study comparing clinical presentation, microbiology, computed tomography, surgical findings and histology

The aim of this study was to obtain comprehensive data on clinical presentation, microbiology, computed tomography, surgical findings and histology in acute, sub-acute and chronic mastoiditis. We performed a prospective, observational study in children under 16 years of age presenting to our institution during the 2-year period beginning in April 2000. The children were examined and their condition treated in accordance with a standardized protocol elaborated by the paediatric, otolaryngology (ORL) and radiology departments. Thirty-eight patients were hospitalized (22 with acute mastoiditis, seven with sub-acute mastoiditis, nine with chronic mastoiditis). There were 30 complications present in 21 patients (55%). Streptococcus pyogenes was the most common pathogen (7/24 cases), followed by Streptococcus pneumoniae (4/24 cases). Mastoid surgery was performed in 29 patients. Histology of mastoid tissue revealed predominantly acute inflammation in two cases, mixed acute/chronic inflammation in 19 cases and predominantly chronic inflammation in seven cases. Radiologic data were evaluated retrospectively. Spiral, volume-based high-resolution (HR) computed tomography (CT) of the temporal bone had a sensitivity of 100%, specificity of 38%, positive predictive value (PPV) of 50% and negative predictive value (NPV) of 100% in detecting coalescence of mastoid trabeculae. Cranial CT with contrast had a sensitivity of 80%, specificity of 94%, PPV of 80% and NPV of 94% in identifying intra-cranial extension. Conclusion: histological evidence suggests that sub-acute/chronic infection underlies not only sub-acute and chronic mastoiditis, but most cases of acute mastoiditis as well. HR-CT of the temporal bone is effective in ruling out coalescence. Cranial CT is valuable in identifying intra-cranial extension. Cranial and HR-CT are recommended in the examination of children with mastoiditis.     

Retrospective analysis of the prognostic value of electroencephalography patterns obtained in pediatric in-hospital cardiac arrest survivors during three years.

OBJECTIVE: To test the hypothesis that electroencephalography has prognostic value in children after in-hospital cardiac arrest. DESIGN: Single-center, retrospective chart review. SETTING: Urban tertiary care children's hospital, January 2001 to July 2004. PATIENTS: Thirty-four consecutive children were identified from a registry of all patients resuscitated for cardiac arrest. Inclusion criteria were age >44 wks postmenstrual age to 18 yrs, survival after in-hospital cardiac arrest >24 hrs, and undergoing electroencephalography within 7 days after the cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Prearrest, event, cardiopulmonary resuscitation, and postresuscitation variables were collected. Neurologic outcome was assessed by Pediatric Cerebral Performance Category (PCPC). Prearrest PCPC was estimated from chart review. Change in PCPC >1 or death between prearrest and time of hospital discharge was defined as poor neurologic outcome. Experts blinded to PCPC outcomes scored electroencephalographs from 1 (normal) to 5 (isoelectric). Sensitivity/specificity analysis and receiver operating characteristic curve were developed with each electroencephalography grade cutoff. Of 184 consecutive patients who had cardiac arrests in our registry, 107 survived >24 hrs, and 83 met study criteria. Thirty-four patients had electroencephalography within the first 7 days after the cardiac arrest. Among those, 16 (47%) patients had good neurologic outcome defined as no change in PCPC, and 18 (53%) died or had poor neurologic outcome. Univariate analysis showed that a higher electroencephalography score performed within 7 days was associated with poor neurologic outcome (p < .05). Positive predictive value of electroencephalography grade 4-5 for poor neurologic outcome was 90%, and negative predictive value of electroencephalography grade 1-2 for poor neurologic outcome was 91%. CONCLUSIONS: In a single-center consecutive case series, electroencephalography background patterns during the initial 7 days after in-hospital cardiac arrest were associated with neurologic outcome in children.     

Differential effects of intrauterine and postnatal brain growth failure in infants of very low birth weight

We investigated the contribution of brain growth failure to outcome in infants of very low birth weight (VLBW; less than 1.5 kg) who were appropriate for gestational age (AGA; n = 379) or small for gestational age (SGA; n = 102). Growth was assessed at birth, term, and 8 and 20 months' corrected age and results of a Bayley Mental Developmental Index (MDI) and neurologic examination were evaluated at 20 months of age. Both groups had similar 20-month MDI scores (93 vs 90) and similar rates of neurologic impairment (14% vs 10%). More SGA infants (25%) than AGA infants (14%) had a subnormal head circumference at 8 months' corrected age, indicating failure to catch up in head growth. Subnormal head size at 8 months predicted the 20-month MDI score for both groups. However, multivariate analysis indicated that, whereas subnormal 8-month head size was directly associated with the MDI score in AGA children, in SGA children 8-month head size was not significantly related to the MDI score when neonatal illness, neurologic impairment, socioeconomic status, and race were controlled for. We conclude that in AGA VLBW infants, subnormal head size at 8 months results from major neonatal illness and has adverse later effects. In SGA infants, subnormal head size at 8 months has many causes, including growth retardation in utero, which may not have an adverse effect on outcome; if subnormal head size is superimposed with neonatal illness, a poorer outcome is likely.     

Outcome of hematopoietic stem cell transplantation in severe combined immune deficiency with central nervous system viral infection

BACKGROUND: Patients with severe combined immunodeficiency and preexisting viral pneumonitis formally had a poor outcome from hematopoietic stem cell transplantation. With inhaled steroid and antitumor necrosis factor alpha antibody treatment, results improved. The poor outcome of patients with viral central nervous system infection prompted this retrospective single center review. RESULTS: Eight of 71 patients with severe combined immunodeficiency transplanted since 1987 were identified with viral central nervous system infection (adenovirus [1], cytomegalovirus [2], Epstein-Barr virus [2], parvovirus [1], varicella zoster virus [1], human herpesvirus 6 [1]). Nonspecific neurologic symptoms included drowsiness, irritability, head lag, fisting and floppiness. Later symptoms included unresponsiveness, apnea, posturing, hypotonia, hyperreflexia and seizures. All had neuroradiologic investigations. Only one had an initially normal computed tomography scan. Magnetic resonance image abnormalities included cerebral atrophy, basal ganglia changes, diffuse leukoencephalopathy, and multifocal mass lesions. Five patients had virus identified from cerebrospinal fluid by polymerase chain reaction and brain tissue examination from 3 patients identified human herpesvirus 6, adenovirus type 41 and varicella zoster virus. Three children remain alive, 2 received replete marrow and one remains untransplanted. Others who received T cell depleted marrow died of neurologic sequelae. CONCLUSION: Outcome of viral central nervous system infection after hematopoietic stem cell transplantation for severe combined immunodeficiency is poor, particularly associated with T cell depleted marrow.     

Intracranial tuberculosis in children: CT appearance and clinical outcome

We retrospectively evaluated the CT studies of 9 children who presented with intracranial tuberculosis during 1981–1987, and compared their radiographic appearance with the clinical outcome. The most common radiographic findings were: 1) ventriculomegaly (7/9), 2) tuberculoma formation (6/9), and 3) infarction (4/9). Of 7 patients with ventriculomegaly, 3 required a ventricular shunt and 2 had spontaneous resolution of ventricular dilatation. Four children with ventriculomegaly were moderately or severely retarded, one had cognitive dysfunction, and one was neurologically normal. Four of six children with tuberculoma also had infarction and/or ventriculomegaly; of these four children, three were moderately or severely retarded. Two patients with tuberculoma as the only intracranial abnormality had complete resolution of the granuloma with normal neurologic outcome following antituberculous therapy. The four children with large vessel infarction also had ventriculomegaly; three had poor clinical outcome. The presence of tuberculoma alone is not necessarily predictive of poor neurologic outcome; age less than 20 months, infarct, and/or ventriculomegaly are usually associated with sequelae.     

Clinical indicators of intracranial lesion on computed tomographic scan in children with parietal skull fracture

We conducted a review of 98 cases of pediatric traumatic parietal skull fracture in which computed tomographic (CT) scans of the head were obtained during a seven-year period. There were 69 instances of an associated intracranial lesion identified in 47 children, including parenchymal injury (23), epidural hematoma (17), subdural hematoma (11), cerebral edema (ten), and subarachnoid hemorrhage (eight). Compared with 51 other children with parietal skull fracture and normal CT scans, the clinical characteristics significantly associated with the presence of an intracranial lesion were symptoms of neurologic dysfunction (loss or altered level of consciousness and/or seizure activity), neurologic compromise on examination (altered level of consciousness and/or focal deficit), or complicated skull fracture (bilateral, diastatic, and/or depressed). Of the 47 children with an intracranial lesion on CT scan, 44 had at least one of these significant clinical characteristics (sensitivity, 93%; specificity, 50%; positive-predictive value, 62%; and negative-predictive value, 96%). Children who sustain traumatic parietal skull fracture commonly experience associated intracranial injury. Those with evidence of neurologic deficit or complicated skull fracture are at particularly high risk, and should receive cranial CT scan evaluation.     

Pediatric minor closed head injury

Many studies have found conflicting evidence over the use of clinical indicators to predict intracranial injury in pediatric mild head injury. Although altered mental status, loss of consciousness, and abnormal neurologic examination have all been found to be more prevalent among head-injured children, studies have observed inconsistent results over their specificity and predictive value. Children older than 2 years have been evaluated, managed, and studied differently than those less than 2 years old. Evidence strongly supports a lower threshold to perform a CT scan in younger children because they have a higher risk of significant brain injury after blunt head trauma.     

The use of repeated head computed tomography in pediatric blunt head trauma: factors predicting new and worsening brain injury.

OBJECTIVE: Opinion is divided on the value of repeat head computed tomography for guiding clinical management of pediatric patients with blunt head trauma. This study describes the prevalence of worsening brain injury on repeat computed tomography, predictors of worsening computed tomography findings, and the frequency of neurosurgical intervention after the repeat computed tomography. DESIGN: Retrospective cohort study. SETTING: All patients were admitted to a level I pediatric trauma center between 1994 and 2003. PATIENTS: Children <15 yrs old with two or more head computed tomographies following hospital admission for blunt head trauma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed the imaging reports to determine injury progression. Potential predictors of worsening computed tomography findings and neurosurgical intervention were recorded by chart review. Logistic regression and recursive partitioning were used to identify predictors. Twenty percent (50 of 257) of patients with mild head injury had worsening computed tomography findings, and three patients (1%) had subsequent neurosurgical intervention. Patients with moderate and severe head injuries were more likely to have worsening computed tomography findings (107 of 248; 43%) and to have neurosurgical intervention (15 of 248; 6%). In most surgical patients, repeat computed tomography was preceded by rapid decline in neurologic status or elevated intracranial pressure. Stratification based on four clinical factors (initial head injury severity, any intraparenchymal finding on initial computed tomography, normal findings on initial computed tomography, coagulopathy) identified 100% of the surgical patients and 89% of patients with worsening brain injuries on the repeat computed tomography. CONCLUSIONS: Repeat head computed tomography imaging is frequently used. About 30% of repeated computed tomographies showed new or worsening brain injury. However, worsening brain injury on repeat computed tomography rarely resulted in neurosurgical intervention. Patients with moderate or severe head injury and intraparenchymal injuries were more likely to show worsening brain injury and undergo neurosurgical intervention.     

Cerebral infarction in the term newborn: clinical presentation and long-term outcome

OBJECTIVE: We evaluated the long-term neurodevelopmental outcome of cranial computed tomography (CT)-documented cerebral infarction in term neonates to ascertain factors that would help to predict the risk of subsequent neurodevelopmental sequelae in early childhood. STUDY DESIGN: From 1983 to 1997, all surviving neonates from two level III neonatal intensive care units were prospectively identified and subsequently assessed in childhood. Clinical presentation was characterized by retrospective chart review and blinded re-reading of computed tomography (CT) scans. Perinatal events were compared with neurodevelopmental outcome. RESULTS: Forty-six children were followed up for a mean of 42.1 months (range, 18-164 months). Neurodevelopmental outcome was normal in 15 and abnormal in 31. A single disability was present in 8, and multiple disabilities were present in 23. Cerebral palsy was present in 22 and cognitive impairment in 19. Abnormal findings on neurologic examination at discharge and seizures in the neonatal period were associated with the presence of one or more childhood disabilities. The site or laterality of the vascular distribution of the lesion on neonatal CT did not correlate with long-term outcome. CONCLUSION: After cerebral infarction in the neonatal period, one third of term infants have normal long-term development. Neonatal seizure history and the findings on neurologic examination at discharge help in counseling parents about the possible long-term outcome of neonatal stroke.     

小儿病毒性脑炎近期预后的预警因素分析

目的　回顾性分析小儿病毒性脑炎的临床资料 ,探讨影响近期预后的预警因素。方法　对 1997～ 2 0 0 3年上海第二医科大学附属新华医院收治的 10 1例病毒性脑炎患儿的临床表现及实验室检查进行回顾性分析 ,对近期预后进行评估 ,采用SPSS 10 0统计软件分析 ,寻找可能的预警因素。结果　近期预后差的患儿意识障碍持续时间、发热时间、惊厥发作时间均明显长于预后好的患儿 ( P <0 0 1)。预后差的患儿入院时多伴有惊厥 ( P <0 0 1) ,肢体运动障碍 (P <0 0 1) ,颅神经麻痹 (P <0 0 1)及其他脏器功能损害 (P <0 0 1)。其中 ,间歇性惊厥发作时间 (OR值 9 35 7,P =0 0 0 2 )是影响近期预后的重要临床预警因素。近期预后差的患儿脑脊液白细胞数低于预后好的 (P <0 0 1) ,脑电图高度异常的比例高 (P <0 0 1) ,脑电图恢复正常较慢 (P <0 0 1) ,多伴有影像学异常 (P <0 0 1)及低钠血症 (P <0 0 1)。其中 ,脑电图恢复慢是近期预后差的实验室预警因素。结论　小儿病毒性脑炎近期预后差的预警因素是惊厥发作时间长、脑电图恢复慢     

Derivation of the children's head injury algorithm for the prediction of important clinical events decision rule for head injury in children.

BACKGROUND: A quarter of all patients presenting to emergency departments are children. Although there are several large, well-conducted studies on adults enabling accurate selection of patients with head injury at high risk for computed tomography scanning, no such study has derived a rule for children. AIM: To conduct a prospective multicentre diagnostic cohort study to provide a rule for selection of high-risk children with head injury for computed tomography scanning. DESIGN: All children presenting to the emergency departments of 10 hospitals in the northwest of England with any severity of head injury were recruited. A tailor-made proforma was used to collect data on around 40 clinical variables for each child. These variables were defined from a literature review, and a pilot study was conducted before the children's head injury algorithm for the prediction of important clinical events (CHALICE) study. All children who had a clinically significant head injury (death, need for neurosurgical intervention or abnormality on a computed tomography scan) were identified. Recursive partitioning was used to create a highly sensitive rule for the prediction of significant intracranial pathology. RESULTS: 22,772 children were recruited over 2 1/2 years. 65% of these were boys and 56% were <5 years old. 281 children showed an abnormality on the computed tomography scan, 137 had a neurosurgical operation and 15 died. The CHALICE rule was derived with a sensitivity of 98% (95% confidence interval (CI) 96% to 100%) and a specificity of 87% (95% CI 86% to 87%) for the prediction of clinically significant head injury, and requires a computed tomography scan rate of 14%. CONCLUSION: A highly sensitive clinical decision rule is derived for the identification of children who should undergo computed tomography scanning after head injury. This rule has the potential to improve and standardise the care of children presenting with head injuries. Validation of this rule in new cohorts of patients should now be undertaken.     

Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection

OBJECTIVE: To determine the ability of neonatal clinical, audiologic, and computed tomography (CT) findings to predict long-term neurodevelopmental outcome in children with symptomatic congenital cytomegalovirus (CMV) infection. METHODS: Longitudinal cohort study of children (n = 41) with symptomatic congenital CMV infection evaluated at birth and followed up with serial age-appropriate neurodevelopmental testing. The performance of birth characteristics as predictors of long-term outcome were determined, and clinical and CT scoring systems were developed and correlated with intellectual outcome. RESULTS: Microcephaly was the most specific predictor of mental retardation (100%; 95% CI 84.5-100) and major motor disability (92.3%; 95% CI 74.8-99). An abnormality detected by CT was the most sensitive predictor for mental retardation (100%; 95% CI 82.3-100) and motor disability (100%; 95% CI 78.2-100). A highly significant (P <.001) positive correlation was found between head size at birth and the intelligence/developmental quotient (IQ/DQ). Approximately 29% of children had an IQ/DQ >90. There was no association between sensorineural hearing loss at birth and cognitive outcome. However, children with sensorineural hearing loss on follow-up (congenital and late-onset) had a lower IQ/DQ (P =.006) than those with normal hearing. CONCLUSIONS: The presence of microcephaly at birth was the most specific predictor of poor cognitive outcome in children with symptomatic congenital CMV infection, whereas children with normal findings on head CT and head circumference proportional to weight exhibited a good cognitive outcome.     

Cerebral vascular accident during the recovery phase of hemolytic uremic syndrome

The hemolytic uremic syndrome (HUS) of children is characterized by microangiopathic hemolytic anemia and acute renal failure. Although a wide spectrum of neurologic symptoms are commonly observed in patients with HUS, the pathogenesis of the central nervous system (CNS) impairment of HUS is often unclear. Microthrombi of cerebral vessels similar to those demonstrated in the kidneys have been reported. The neurologic manifestations generally occur during the early and active phase of the disease. We report a 4 year old boy with HUS who suddenly developed a dense hemiplegia subsequent to hematological and a marked nephrological recovery. The child's cranial axial tomography scan demonstrated a large area of infarction in the region of the right basal ganglia. Follow up examination eight weeks after insult revealed a distinct neurologic recovery with mild loss of fine motor function of the left hand and weakness of the left leg.     

Population cohort associating chorioamnionitis, cord inflammatory cytokines and neurologic outcome in very preterm, extremely low birth weight infants

Intrauterine inflammation may relate to neurologic disability among preterm children. We investigated the relationship between chorioamnionitis, cord serum cytokines, and neurologic outcome. Sixty-one consecutively born very preterm extremely low birth weight (ELBW) infants were prospectively enrolled. Histologic inflammation in placenta and umbilical cord and vascular pathology were evaluated. Cord sera were analyzed for five proinflammatory cytokines. Serial brain ultrasound and magnetic resonance imaging were performed for evaluation of intraventricular hemorrhage (IVH grade I-III) and white matter damage (WMD: cystic periventricular leukomalacia or IVH grade IV). Neurologic and neurocognitive outcomes were assessed at the corrected age of 2 y. The incidences of HCA, WMD, and abnormal neurologic outcome were 48%, 13% and 19%, respectively. HCA or high IL-6 in cord serum predicted spontaneous preterm labor with high accuracy. HCA increased the risk of IVH grade II-III. In HCA, without either clinical chorioamnionitis or histologic placental perfusion defect, the children had a low risk of WMD (0%) and a low risk of abnormal neurologic outcome (6%). In HCA, the concentration of IL-6 in cord serum was lower in children with abnormal neurologic outcome than in children with normal neurologic outcome. In HCA and placental perfusion defect (compound defect) the risk of abnormal neurologic outcome was high. Compound placental defect and WMD additively predicted abnormal neurologic outcome. We propose that HCA together with other insults (placental perfusion defect or maternal systemic infection) increases the risk of poor neurologic outcome in very preterm ELBW infants.     

Cerebral perfusion pressure and auditory brain-stem responses in childhood CNS diseases

Intracranial hypertension, complicating CNS diseases of childhood, reduces effective cerebral perfusion pressure (CPP) with resultant cerebral ischemia. The auditory brain-stem evoked response (ABR) is an important diagnostic tool that enables evaluation of brain-stem function and prognostication during the acute stage of the illness. We studied CPP and ABRs in 25 infants and children with CNS infection and cerebral ischemia. In all survivors, CPP could be maintained above 30 mm Hg, and the ABR remained normal or with partial pathology. In nonsurvivors, CPP could not be maintained above this level, and the ABR waves were completely absent. Long-term outcome was not correlated with the minimal CPP recorded during the disease or with examination of the ABR.     

Clinical predictors of outcome in encephalitis.

Twenty five patients with encephalitis were studied prospectively, and their clinical and virological features compared with outcome. Among 22 patients with laboratory confirmation of virus infection, evidence of direct effect on the central nervous system by the virus occurred significantly more often both in those with a monophasic illness compared with those with a biphasic illness, and in those with focal neurological signs localising in the cerebral hemispheres compared with those without such signs. Young age at presentation, low score on the Glasgow coma scale, disruption of oculocephalic responses, and laboratory evidence of virus infection within the central nervous system were significantly associated with poor outcome. Computed tomography results, concentrations of creatine phosphokinase BB isoenzyme in cerebrospinal fluid, and procoagulant activity in cerebrospinal fluid were not predictive of outcome.