Neurological and perceptual-motor outcome at 5 - 6 years of age in children with neonatal encephalopathy: relationship with neonatal brain MRI

OBJECTIVE: The aims of this study were 1) to determine the incidence of minor neurological dysfunction and perceptual-motor difficulties in children aged 5-1/2 -- 6-1/2, who had been born full-term but presented with neonatal encephalopathy (NE) and low Apgar scores and 2) to examine the relationships between the presence/absence of these difficulties with neonatal brain MRI. PARTICIPANTS AND METHODS. Sixty-eight full-term infants with one minute Apgar scores less than or equal to 5 and neurological abnormalities during the first 48 hours after birth were included in the study. All children had a neonatal MRI brain scan. Surviving infants were assessed between the age of 5 and 6 years using the Touwen Examination, the Movement ABC and the WPPSI-R. RESULTS: Fifteen of the 68 infants (22 %) died in the neonatal period. Of the 53 surviving infants, 19 (36 %) had cerebral palsy. The remaining 34 were considered normal at 2 years of age but, when assessed at school age, 8 (15 %) had minor neurological dysfunction and/or perceptual-motor difficulties, 1 (2 %) had only cognitive impairment and 25 (47 %) were normal. The outcome largely reflected the pattern of lesions on brain imaging. While 83 % of those with a normal outcome had normal scans or minimal white matter lesions, 80 % of those with minor neurological dysfunction and/or perceptual-motor difficulties had mild or moderate basal ganglia or more marked white matter lesions. CONCLUSION. Continued surveillance is recommended for children with apparently normal outcome at two years of age after NE, particularly when abnormalities are detected on brain MRI.     

Primary Intraventricular Hemorrhage: Yield of Diagnostic Angiography and Clinical Outcome

Introduction  Primary intraventricular hemorrhage (IVH), bleeding in the ventricular system without a discernable parenchymal component, is a rare neurological disorder. To better define the features of primary IVH and the yield of diagnostic angiography in this condition, we retrospectively analyzed all cases of primary IVH evaluated at a tertiary referral hospital over a 6-year period and performed a systematic review of the literature. Methods  For the retrospective case series, all patients with primary IVH admitted to the neurovascular service at a single tertiary referral center over a 6-year period were identified by screening a departmental database. For the systematic review of the literature, all case series of patients with primary IVH diagnosed by computed tomography were identified in the Medline database. Results  From the systematic review, the majority of patients with spontaneous primary IVH presented with headache (69%), nausea/vomiting (53%), and altered mental status (66%). Most primary IVH patients had associated hydrocephalus (62%), and about one-third required ventricular drainage (34%). Diagnostic cerebral angiography was positive for a bleeding source in 56%. The two most common causes identified by angiography were arteriovenous malformations (58% of positive angiograms) and aneurysms (36% of positive angiograms). Approximately one-third of patients with primary IVH do not survive hospital discharge (39%). Patient age and amount of IVH independently predicted in-hospital mortality. Conclusions  Primary IVH is a rare form of intracerebral hemorrhage, with varying short-term outcomes that depend on patient age and the extent of intraventricular hemorrhage. The yield of diagnostic cerebral angiography in the setting of primary IVH is very high. The two most common causes of primary IVH identified on angiography are arteriovenous malformations and aneurysms. Routine catheter angiography in the setting of primary IVH is warranted. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Prediction of cognitive abilities at the age of 5 years using developmental follow-up assessments at the age of 2 and 3 years in very preterm children

Aim This study investigated prediction of separate cognitive abilities at the age of 5 years by cognitive development at the ages of both 2 and 3 years, and the agreement between these measurements, in very preterm children. Methods Preterm children (n=102; 44 males; 58 females) with a gestational age less than 30 weeks and/or birthweight less than 1000g were assessed at the ages of 2 and 3 years using the second edition of the Bayley Scales of Infant Development, the Child Behaviour Checklist, and a neurological examination, and at the age of 5 years using the third edition of the Wechsler Preschool and Primary Scale of Intelligence. Results Cognitive development at ages 2 and 3 years explained 44% and 57% respectively of full‐scale intelligence at the age of 5 years. Adding psychomotor, neurological, and behavioural outcomes to the regression model could not or only marginally improve the prediction; adding perinatal and sociodemographic characteristics to the regression model increased the explained variance to 57% and 64% respectively. These percentages were comparable for verbal intelligence. Processing speed quotient and especially performance intelligence were predicted less accurately. Interpretation Not all aspects of intelligence are predicted sufficiently by the Mental Development Index at ages 2 and 3 years. Follow‐up of very preterm children until at least the age of 5 years is needed to distinguish between different aspects of cognitive development.     

Autism spectrum disorder diagnoses in Stockholm preschoolers

The aims of this study were to estimate prevalence rates of children with autism spectrum disorder (ASD) diagnoses in a cohort of 6-year-old children with birth year 2002, referred to the Autism Centre for Young Children, serving the whole of Stockholm county and on the basis of the available data discuss clinical aspects of assessment, habilitation and follow-up.Records of 142 of a total of 147 (123 boys and 24 girls) identified children with ASD diagnoses were scrutinised with respect to type of diagnosis, cognitive level, other developmental disorders and medical/neurological disorders. The overall prevalence of such disorders was 6.2/1000 (95% confidence interval 5.2–7.2/1000). The rates of learning disability/mental retardation, developmental delay without a specified cognitive level and normal intelligence constituted about one third, respectively. AS and atypical autism tended to be diagnosed more often at age 5–6 years while AD with learning disability/mental retardation was more often diagnosed at age 3–4 years. The awareness of ASDs has resulted in increasing numbers of children being diagnosed at young ages. We conclude that it is important to take into account these children's broader developmental profiles, need for repeated assessment of cognitive functions and follow-up over time and also the requirement for medical/neurological consideration and work-up.     

Cognitive deterioration and electrical status epilepticus during slow sleep

The results of long-term follow-up of 10 children with global or specific cognitive deterioration and, on the electroencephalogram, electrical status epilepticus during sleep (ESES) are described. They were referred because of cognitive deterioration and underwent repeated neurological and neuropsychological examinations and all-night electroencephalography. A previous cognitive level was known or could be estimated in all. Seven children had a continuous spikes and waves during sleep (CSWS) syndrome, with global cognitive deterioration in four and more specific cognitive decline in three, and another three children had Landau-Kleffner syndrome (LKS). Of the last three, two children never had seizures, while the other had localization-related epilepsy. No children experienced aggravation of clinical seizures. However, therapy was disappointing. Cognitive dysfunction did not respond to valproate and/or benzodiazepines in 9 of the 10 children. A frontal epileptic focus was found in 5 of 7 children with CSWS, and a left temporal focus in 2 of 3 children with LKS. The ESES persisted in CSWS for 5-9 years and in LKS for 1-5 years, and disappeared at puberty. Good cognitive recovery after disappearance of ESES occurred in only one child, and partial recovery in four. An unfavorable prognosis of cognitive deterioration seems to be related to long-duration ESES and/or early onset epileptic activity. The authors are of the opinion that cognitive deterioration in children, with or without manifest epileptic seizures, should mandate electroencephalographic investigation during sleep.     

Neurodevelopmental outcome of hydrocephalus following intra-/periventricular hemorrhage in preterm infants: short- and long-term results

Over a 5-year period (1984–1988) intra- and periventricular hemorrhage (IVH/PVH) was observed in 299 preterm infants. Sixty-eight infants developed posthemorrhagic hydrocephalus (PH); of these, 23 infants died and 40 infants could be followed up for assessment of neurological development (5 patients were lost to follow-up). At 1 year of corrected age 15% (25% at 5 year follow-up) of the infants were determined to have developed normally, 35% (25% at 5-year follow-up) showed mild neurological symptoms and/or slight developmental delay, 32.5% (28% at 5-year follow-up) had handicaps and/or moderate mental retardation, and 17.5% (22% at 5-year follow-up) had severe handicaps and/or severe mental retardation. There was a significantly worse outcome in infants with grade 4 IVH/PVH (P<0.05) and a significantly worse outcome in the group requiring ventriculoperitoneal (VP) shunt (P<0.05). The results at 1 year of corrected age proved to be a quite realistic predictor of neurological functioning at 5 years of age (80% predicted correctly in the nonshunted-group — one patient lost to follow-up; 95% predicted correctly in the shunted group — four patients lost to follow-up). Cystic periventricular leukomalacia had been diagnosed in 7 (10%) patients and was associated with poor neurodevelopmental outcome. Gestational age, birth weight, time of shunt placement, and peripartum asphyxia had no significant influence on neurodevelopmental outcome. Infants with shunt infections and a high number of shunt revisions were found to have a significantly worse neurodevelopmental outcome (P<0.01).     

Spontaneous intraventricular haemorrhage

Summary Twenty-one patients with spontaneous intraventricular haemorrhage (IVH) were reviewed with particular reference to the clinical outcome. Based on clinical and computed tomography (CT) findings, as well as possible mechanisms governing the formation of IVH, we were able to identify two separate groups: (1) patients with haemorrhage into ventricles without clinical or CT evidence of a lesion in adjacent brain parenchyma and (ii) patients with IVH occurring as a result of erosion of the ventricular wall by either a juxtaventricular small haematoma shown by CT and/or IVH with focal neurological deficit. Out of 12 patients in the first group, 8 survived and resumed their previous activities; in the second group (i.e. patients with clinical and/or CT evidence of adjacent intraparenchymal bleeding only three patients survived, two with considerable handicap. The overall prognosis, however, was significantly better in patients with IVH of unknown cause. Altered sensorium as an initial presentation was associated with a grave prognosis, irrespective of the cause of IVH. The outcome was not affected by the age of patient or the amount of blood within the ventricles. Our data suggest a favourable outcome in a relatively large percentage of patients with spontaneous IVH, if there is no clinical or CT evidence of concomitant parenchymal bleeding. Hence we question the notion that there is a grave prognosis in all kinds of IVH.     

Children exposed to valproate in utero--population based evaluation of risks and confounding factors for long-term neurocognitive development

PURPOSE: To evaluate neurological and cognitive functioning of school-aged (> or =6 years) children exposed to valproate monotherapy in utero in a population based, evaluator-blinded, controlled study. METHODS: Studied children (N=39, aged 6.6-13.4 years) and their mothers were identified through a population based pregnancy registry. Mothers with carbamazepine monotherapy and mothers with epilepsy but without antiepileptic drug (AED) treatment during pregnancy and their age and gender matched children served as controls. Hospital records were reviewed and neurological examination (Touwens test), intelligent quotients (IQ) of mothers (WAIS), and children (WISC-III) and neuropsychological assessment of children (NEPSY) were performed evaluator-blinded. RESULTS: The prevalence of low intelligence (FIQ<80) was 19% (4/21) and the prevalence of exceptionally low intelligence (FIQ<70) 10% (2/21) in valproate (VPA) monotherapy exposed children. Children exposed to carbamazepine (CBZ) and children of women with epilepsy but without AED exposure during pregnancy had all at least low average intelligence. The mothers using valproate scored significantly lower (p<0.05) in FIQ, VIQ and PIQ tests and had also significantly lower (p=0.035) educational level. Altogether 21% (8/39) of the children had minor neurological dysfunctions. CONCLUSIONS: In a population based setting inheritance and cumulating environmental factors may partly explain the increased prevalence of neurocognitive symptoms in children exposed to valproate in utero although concern about the possible long-term effects of intrauterine valproate exposure does exist.     

Outcome after prolonged convulsive seizures in 186 children: low morbidity, no mortality

Prolonged convulsive seizures are a common neurological emergency and a potential cause of neuronal damage and functional sequelae. We explored the role of seizure duration and various background factors for neurological sequelae in children with prolonged convulsive seizures. The population-base of this study was all children (age < 16 years) who had been admitted to the Tampere University Hospital, Finland between 1993 and 1999 with convulsive seizures lasting more than 5 minutes. Patients were followed up individually (mean length of follow-up 2 years 1 month, range 0 to 7 years 8 months). All available data on the prolonged seizure episodes and clinical follow-up were analyzed retrospectively by a detailed review of all medical charts and records. In 186 children (94 males, 92 females; mean age 4 years 5 months, SD 3 years 10 months, range 1 month to 15 years 4 months) there were 279 separate convulsive seizure episodes lasting over 5 minutes, yielding an annual incidence of 47.5 out of every 100000 episodes. Seizure aetiology was idiopathic in 26.2% of episodes, febrile in 41.9%, remote symptomatic in 28%, and acute symptomatic in 3.9% of episodes. Mean duration of all seizure episodes was 42.5 minutes (SD 46.1 minutes) and was significantly correlated with the aetiology: shortest in the febrile group (mean 35.4 minutes) and longest in the acute symptomatic group (mean 88.6 minutes; p < 0.001). There was no mortality related directly to these acute seizure episodes. The most common sequela was an onset of epilepsy in 40 children (22%). Permanent neurological sequelae were noted in only four patients (2.2%; mean seizure duration 16 minutes) and non-permanent sequelae in six patients (3.2%; mean seizure duration 38 minutes). Neurological sequelae of prolonged convulsive seizures in children are rare and are related to aetiological factors rather than the duration of a single seizure. The role of acute seizures in the evolution of epilepsy in children remains obscure.     

Uncommon causes of intraventricular hemorrhage

The advent of CT has lead to discovery of a wide variety of unusual causes of intraventricular hemorrhage (IVH) and hence to the shifts in the proportional incidence of its different etiologies. From 96 patients with IVH, 7 uncommon cases of intracerebral hemorrhage (ICH) associated with IVH, including 2 due to anticoagulation treatment, 1 because of thrombolytic therapy, 1 due to thrombocytopenia, 2 as operative complications and 1 due to metastatic brain tumor are presented. In patients with blood disorders-related IVH the clinical presentation was similar to 'stroke in evolution', and the severity of IVH correlated with neurological deficit on admission and outcome of 3/4. All of the patients were treated with external ventricular drainage (EVD), 1 underwent partial evacuation of ICH in addition. 4 (57%) patients, including 3 with coagulation defect deceased. The peculiar aspects of uncommon causes of IVH are discussed on the basis of a review of the literature. The authors suggest that a standardized differentiated protocol should be adopted for the management of every uncommon type of IVH. An active attitude towards the evacuation of blood disorders-related ICHs and IVHs seems to be justified.     

Relation between visual perceptual impairment and neonatal ultrasound diagnosis of haemorrhagic-ischaemic brain lesions in 5-year-old children

Visual-perceptual abilities were assessed in 5-year-old children with the following neonatal neurological conditions: born preterm with normal ultrasound scan (NL, n=17); born preterm with ultrasound diagnosis of intraventricular haemorrhage (IVH, n=17); born preterm with ultrasound diagnosis of periventricular leukomalacia (PVL, n=12); born term with hypoxic-ischaemic encephalopathy (HIE, n=11). Visual-perceptual ability was evaluated with the L94: eight visual-perceptual tasks designed to evaluate different aspects of visual perception at the preschool level in children with multiple disabilities. Impairment was established in comparison to the performance age obtained on non-verbal intelligence subtests, instead of chronological age. Frequency of L94 impairment was highest in children with PVL, while children with IVH did not differ from the NL control group. Impairment rates were increased also in children with transient periventricular echodensities, and in children with HIE. Impairments were only moderately related to the delay of visual acuity maturation in infancy.     

Characterization and comparison of autistic subgroups: 10 years' experience with autistic children

To summarize our 10-year experience with autistic children at the Tel Aviv Child Development Center, the files of all 55 children with autism treated at our center over a 10-year period were retrospectively reviewed. Particular attention was addressed to the value of the medical work-up in detecting the etiology of autism and to factors differentiating infantile autism (IA) from autistic-like behavior (ALB). Twenty-four subjects (44%) had IA and 31 (56%) had ALB. These subgroups were compared for demographic, perinatal, familial, neurological, and psychological findings, and outcome at discharge. Associated medical conditions and the yield of metabolic work-up and neuroimaging and electroencephalography studies are discussed. The two subgroups differed only in severity of autistic symptoms and cognitive function (P<0.05), but not in demographic or neurobiological findings. It was concluded that IA and ALB are similar conditions, and autism has a wide continuum of clinical expressions.     

Neurological involvement in hemolytic-uremic syndrome

Of 44 children with hemolytic-uremic syndrome seen at Milwaukee Children's Hospital, 15 (34%) had neurological involvement. This group contained 8 boys and 7 girls, with a mean age of 3 1/4 years. Twelve patients had seizure within 48 hours of admission. Seizures were associated with hypertension, fever, hyponatremia, or hypocalcemia. Other neurological symptoms included altered consciousness, behavioral changes, diplopia, and dizziness. Hemiparesis (4 patients), eye involvement (7 patients), decerebrate posturing (2 patients), and ataxia (1 patient) were present on physical examination. Cerebrospinal fluid examination showed increased protein in 4 of 11 patients. Electroencephalograms were abnormal in all 9 patients tested. Computed tomographic and radionuclide scans showed evidence of vascular abnormalities in 4 of the 14 patients studied. Complete neurological recovery occurred in only 6 of the 15 children, while the remaining 6 demonstrated residual hemiparesis, seizures, and cortical visual defect. In those children with neurological involvement, there was a higher incidence of residual hypertension (49% versus 11%), chronic renal damage (40% versus 3.5%), and death (28% versus 0%), suggesting that central nervous system involvement indicates severe hemolytic-uremic syndrome.     

Speech,language, and cognitive development in children with isolated sagittal synostosis

This study investigated the occurrence, nature, and severity of speech, language, and cognitive impairment in 76 children (61 males, 15 females) with isolated sagittal synostosis (ISS) aged 9 months to 15 years 7 months. There was no increased prevalence of global cognitive impairment in the group but there was a high prevalence rate of speech and/or language impairment with 28 (37%) displaying impairment of whom 20 (71%) had moderate or severe impairments that fulfilled the criteria for specific impairments. Prevalence rates were only increased for children over two years of age. Expressive language impairment occurred most frequently. Raised intracranial pressure, peri-neonatal risk factors, otitis media, or being operated were not associated with impairment. Surgery at a later age and a family history of speech and language impairment were both associated with impairments but numbers were small. The findings suggest that children with ISS are at an increased risk of developing speech and language impairment.     

Cerebral lesions in early prematurity: EEG prognostic value in the neonatal period

The new radiological technics show the incidence of intraventricular hemorrhage (IVH), intraparenchymal hemorrhage (IPH), or of porencephaly (PL), in the neonatal period. Discrepancies between the initial extent of lesions and the outcome have been observed. We tried to appreciate the EEG value in infants having had such lesions during the first month of life. We studied serial EEGs and neuroradiological exams in 34 babies: with IVH (group I, 17 cases), with IPH and/or PL (group II, 17 cases). Their gestational age (GA) was between 27 and 34 weeks; they all had a neurological follow-up between one and five years. Infants with favourable outcome (76% in gr. I, 47% in gr. II) had normal or slightly abnormal EEGs, whatever the extent of lesions. Nine babies had very abnormal EEGs (numerous positive rolandic spikes (PRSs) and/or EEG background without physiological rhythms); one developed moderate sequelae, the other 8 major sequelae (2 with infantile spasms). In gr. II, babies with major sequelae had a higher GA than babies with good outcome. The PRSs were more often observed with periventricular lesions than with IVH only and in babies with higher GA; they lasted up to 12 weeks on serial EEGs in one case with porencephaly (major sequelae with infantile spasms); they appeared before scan abnormality in another case which developed later porencephaly (major sequelae). Thus, EEGs give valuable information on brain function and help to forecast outcome in premature babies.     

Eating problems at age 6 years in a whole population sample of extremely preterm children

Aim The aim of this study was to investigate the prevalence of eating problems and their association with neurological and behavioural disabilities and growth among children born extremely preterm (EPC) at age 6 years. Method A standard questionnaire about eating was completed by parents of 223 children (125 males [56.1%], 98 females [43.9%]) aged 6 years who were born at 25 weeks’ gestation or earlier (mean 24.5wks, SD 0.7wks; mean birthweight 749.1g, SD 116.8g), and parents of 148 classmates born at term (66 males [44.6%], 82 females [55.4%]). All children underwent neurological, cognitive, and anthropometric assessment, and parents and teachers completed a behaviour scale. Results Eating problems were more common among the EPC than the comparison group (odds ratio [OR] 3.6, 95% confidence interval [CI] 2.1–6.3), including oral motor (OR 5.2, 95% CI 2.8–9.9), hypersensitivity (OR 3.0, 95% CI 1.6–5.6), and behavioural (OR 3.8, 95% CI 1.9–7.6) problems. Group differences were reduced after adjustment for cognitive impairment, neuromotor disability, and other behaviour problems. EPC with eating problems were shorter, lighter, and had lower mid‐arm circumference and lower body mass index (BMI) even after adjusting for disabilities, gestational age, birthweight, and feeding problems at 30 months. Interpretation Eating problems are still frequent in EPC at school age. They are only partly related to other disabilities but make an additional contribution to continued growth failure and may require early recognition and intervention.     

NON-RIGHT HANDEDNESS AMONG ELBW AND TERM CHILDREN AT EIGHT YEARS IN RELATION TO COGNITIVE FUNCTION AND SCHOOL PERFORMANCE

The relationship between handedness, neurological and cognitive deficits, and school difficulties was investigated in 114 extremely low-birthweight (ELBW) children and 145 term controls at eight years. The prevalence of non-right handedness (left and mixed) was 31 per cent for ELBW children and 19 per cent for controls. ELBW children with neurological impairments were significantly more likely to be non-right handed. No significant differences were noted between right-handed and non-right handed ELBW children and controls on tests of cognitive function, school performance and prevalence of learning difficulties. These findings suggest an association between neurological impairment and non-right handedness, but do not support the hypothesis of early brain insult resulting in subtle cognitive deficits and suboptimal school performance among non-right handed ELBW children.     

Effect of hyperoxic resuscitation on propensity of germinal matrix haemorrhage and cerebral injury

C. O. Chua, G. Vinukonda, F. Hu, N. Labinskyy, M. T. Zia, J. Pinto, A. Csiszar, Z. Ungvari and P. Ballabh (2010) Neuropathology and Applied Neurobiology 36, 448–458
Effect of hyperoxic resuscitation on propensity of germinal matrix haemorrhage and cerebral injury Aims: Intraventricular haemorrhage (IVH) and cerebral injury are major neurological disorders of premature infants. The effect of hyperoxic resuscitation on the occurrence of IVH and cerebral injury is elusive. Therefore, we asked whether hyperoxia during neonatal resuscitation increased the incidence and severity of IVH and cerebral injury in premature newborns. Methods: Premature rabbit pups, delivered by C‐section, were sequentially assigned to receive 100%, 40% or 21% oxygen for 15 or 60 min at birth. The pups were treated with intraperitoneal glycerol at 24‐h postnatal age to determine the incidence and severity of glycerol‐induced IVH. Vascular endothelial growth factor and angiopoietin‐2 genes and protein expression, endothelial proliferation as well as free radical levels and antioxidants were assessed in the germinal matrix, white matter and cortex of pups exposed to 100% oxygen and to 21% oxygen. Results: Exposure with 100% oxygen for 1 h did not adversely exacerbate the incidence of glycerol‐induced IVH in premature rabbit pups. Compared with room air, 100% oxygen enhanced mRNA expression of both vascular endothelial growth factor and angiopoietin‐2 as well as reactive oxygen species levels in the germinal matrix. Hyperoxia did not affect endothelial proliferation, apoptosis or neuronal degeneration in the forebrain. Conclusion: Our data suggest that 100% oxygen exposure for 1 h does not increase the risk of IVH or cerebral injury in premature rabbit pups. Although extrapolating rabbit neural developmental data into humans has obvious limitations, we speculate that hyperoxia of short duration at birth in premature infants may not result in major neurological adverse effects.     

Factors associated with microcephaly at school age in a very-low-birthweight population

The neonatal predictors of microcephaly, defined as a head circumference <5th centile in children born preterm, has not been systematically assessed. Children were drawn from the Developmental Epidemiology Network (DEN) cohort of very low-birthweight children (VLBW: 500-1500g) born from 1991 to 1993 at three sites in the USA. Neurological assessments were carried out among 198 singleton children (mean age 6 years 8 months, SD 0.5 years). Ninety-six children (48.5%) were male. Microcephaly was observed in 30 children (15%) and, using multivariate analysis, it was found to be associated with gestational age <26 weeks and bronchopulmonary dysplasia (BPD). Sonography-defined white-matter damage (WMD, i.e. echolucency or echodensities) was not associated with increased odds of microcephaly, while occurrence of intraventricular hemorrhage (IVH) was in univariate but not multivariate analysis. In analyses that excluded children with IVH/WMD, odds of microcephaly increased in dose-related fashion according to number of days on ventilator: >5 days, OR=4.5; 95%CI=1.4 to 15; >10 days, OR=5.7; 95%CI=1.7 to 19; >15 days OR=8.3; 95% CI=2.3 to 29.2. Among children without BPD, microcephaly was not associated with differences in IQ, while IQ scores among children with BPD or any ventilation were disproportionately lower among those with microcephaly. In multivariate analyses predicting IQ at age 7 years, microcephaly was found to modify the association between neonatal lung disease and IQ.     

Massive intraventricular haemorrhage from aneurysmal rupture: patient proportions and eligibility for intraventricular fibrinolysis

Massive intraventricular haemorrhage (IVH) complicating aneurysmal subarachnoid haemorrhage (SAH) is associated with a poor prognosis. Small observational studies suggest favourable results from fibrinolysis of the intraventricular blood. We performed an observational study on IVH in a large series of patients with SAH to assess the proportion of patients that may benefit from fibrinolytic treatment. From our prospective database we retrieved patients with aneurysmal SAH admitted between January 2000 and January 2005. We calculated the proportion of patients with massive IVH and the proportion of patients that are eligible for fibrinolysis on basis of clinical and CT-scan characteristics and assessed neurological outcome in a treatment strategy without fibrinolysis. Poor neurological condition was defined as World Federation of Neurological Surgeons scale 4 and 5, poor outcome as death or dependence 3 months after SAH. Of the 573 patients admitted with aneurysmal SAH, 59 (10%; 95% confidence interval CI 8–13%) had massive IVH, of which 55 were in poor clinical condition. For these 55 patients, the case-fatality rate was 78% (95% CI 66–88%) and the proportion with poor outcome 91% (95% CI 81–97%). Of the 55 patients, 31 (56%, and 5% of all patients SAH within the study period) fulfilled our eligibility criteria and were considered suitable for intraventricular fibrinolysis. At 3 months, 30 of these 31 eligible patients (97%; 95% CI 85–100%) had a poor outcome. Massive IVH occurs in 10% of patients with aneurysmal SAH. Half of these patients may benefit from intraventricular fibrinolysis. Without fibrinolysis outcome is almost invariably poor in these patients.