A growth chart of brain function from infancy to adolescence based on EEG.

BACKGROUND: In children, objective, quantitative tools that determine functional neurodevelopment are scarce and rarely scalable for clinical use. Direct recordings of cortical activity using routinely acquired electroencephalography (EEG) offer reliable measures of brain function. METHODS: We developed and validated a measure of functional brain age (FBA) using a residual neural network-based interpretation of the paediatric EEG. In this cross-sectional study, we included 1056 children with typical development ranging in age from 1 month to 18 years. We analysed a 10- to 15-min segment of 18-channel EEG recorded during light sleep (N1 and N2 states). FINDINGS: The FBA had a weighted mean absolute error (wMAE) of 0.85 years (95% CI: 0.69-1.02; n = 1056). A two-channel version of the FBA had a wMAE of 1.51 years (95% CI: 1.30-1.73; n = 1056) and was validated on an independent set of EEG recordings (wMAE = 2.27 years, 95% CI: 1.90-2.65; n = 723). Group-level maturational delays were also detected in a small cohort of children with Trisomy 21 (Cohen's d = 0.36, p = 0.028). INTERPRETATION: A FBA, based on EEG, is an accurate, practical and scalable automated tool to track brain function maturation throughout childhood with accuracy comparable to widely used physical growth charts. FUNDING: This research was supported by the National Health and Medical Research Council, Australia, Helsinki University Diagnostic Center Research Funds, Finnish Academy, Finnish Paediatric Foundation, and Sigrid Juselius Foundation.

Without ENMG, detecting pediatric vincristine neuropathy is a challenge.

Objective: Vincristine, a widely used anticancer chemotherapy drug, may cause polyneuropathy (PNP), potentially resulting in permanent functional impairment. We characterized the occurrence and development of vincristine-induced neuropathy (VIPN) in early treatment of childhood leukemia. Methods: This prospective study of 35 pediatric acute lymphoblastic leukemia (ALL) patients comprised systematic clinical and electrophysiological studies at both the time of diagnosis and at least one time point during the first months of treatment. Results: After vincristine treatment, all patients had axonal sensorimotor PNP on electroneuromyography (ENMG) In 34/35 patients, the motor and in 24/35 the sensory responses were decreased. Interestingly, in 3 patients PNP was most prominent in the upper limb. However, some children had no PNP symptoms despite moderate ENMG findings, and not all clinical symptoms were correlated with abnormal ENMG. Conclusions: Pediatric VIPN is a sensorimotor, predominantly motor axonal neuropathy. VIPN can be detected even in its early phase by ENMG, but it is difficult to detect by symptoms and clinical examination only. Significance: Pediatric ALL patients treated with vincristine are at risk of developing VIPN. Since the clinical signs of PNP in acutely ill children are difficult to identify, VIPN can easily be overlooked if ENMG is not performed.

Optimization of time series features to estimate brain age in children from electroencephalography.

Functional brain age measures in children, derived from the electroencephalogram (EEG), offer direct and objective measures in assessing neurodevelopmental status. Here we explored the effectiveness of 32 preselected 'handcrafted' EEG features in predicting brain age in children. These features were benchmarked against a large library of highly comparative multivariate time series features (>7000 features). Results showed that age predictors based on handcrafted EEG features consistently outperformed a generic set of time series features. These findings suggest that optimization of brain age estimation in children benefits from careful preselection of EEG features that are related to age and neurodevelopmental trajectory. This approach shows potential for clinical translation in the future.Clinical Relevance-Handcrafted EEG features provide an accurate functional neurodevelopmental biomarker that tracks brain function maturity in children.

Is epileptiform activity related to developmental language disorder? Findings from the HelSLI study.

Objective: To study if interictal epileptiform discharges (IEDs) are associated with language performance or pre-/perinatal factors in children with developmental language disorder (DLD). Methods: We recorded routine EEG in wake and sleep in 205 children aged 2.9-7.1 years with DLD, without neurologic diseases or intellectual disability. We examined the language performance of the children and collected data on pre-/perinatal factors. Results: Interictal epileptiform discharges were not associated with lower language performance. Children with so-called "rolandic", i.e. centrotemporoparietal, IEDs had better language skills, but age explained this association. Most pre-/perinatal factors evaluated did not increase the risk of rolandic IEDs, except for maternal smoking (OR 4.4, 95% CI 1.4-14). We did not find electrical status epilepticus during slow-wave sleep (ESES)/spike-and-wave activation in sleep (SWAS) in any children. Conclusions: Interictal epileptiform discharges are not associated with lower language performance, and ESES/SWAS is not common in children with DLD. Significance: Routine EEGs do not bring additional information about language performance in children with DLD who do not have any neurologic diseases, seizures, intellectual disability, or regression of language development.

Routine and sleep EEG: Minimum recording standards of the International Federation of Clinical Neurophysiology and the International League Against Epilepsy.

This article provides recommendations on the minimum standards for recording routine ("standard") and sleep electroencephalography (EEG). The joint working group of the International Federation of Clinical Neurophysiology (IFCN) and the International League Against Epilepsy (ILAE) developed the standards according to the methodology suggested for epilepsy-related clinical practice guidelines by the Epilepsy Guidelines Working Group. We reviewed the published evidence using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The quality of evidence for sleep induction methods was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. A tool for Quality Assessment of Diagnostic Studies (QUADAS-2) was used to assess the risk of bias in technical and methodological studies. Where high-quality published evidence was lacking, we used modified Delphi technique to reach expert consensus. The GRADE system was used to formulate the recommendations. The quality of evidence was low or moderate. We formulated 16 consensus-based recommendations for minimum standards for recording routine and sleep EEG. The recommendations comprise the following aspects: indications, technical standards, recording duration, sleep induction, and provocative methods.

Routine and sleep EEG: Minimum recording standards of the International Federation of Clinical Neurophysiology and the International League Against Epilepsy.

This article provides recommendations on the minimum standards for recording routine ("standard") and sleep electroencephalography (EEG). The joint working group of the International Federation of Clinical Neurophysiology (IFCN) and the International League Against Epilepsy (ILAE) developed the standards according to the methodology suggested for epilepsy-related clinical practice guidelines by the Epilepsy Guidelines Working Group. We reviewed the published evidence using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The quality of evidence for sleep induction methods was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. A tool for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the risk of bias in technical and methodological studies. Where high-quality published evidence was lacking, we used modified Delphi technique to reach expert consensus. The GRADE system was used to formulate the recommendations. The quality of evidence was low or moderate. We formulated 16 consensus-based recommendations for minimum standards for recording routine and sleep EEG. The recommendations comprise the following aspects: indications, technical standards, recording duration, sleep induction, and provocative methods.

Poor aEEG background recovery after perinatal hypoxic ischemic encephalopathy predicts postneonatal epilepsy by age 4 years.

OBJECTIVE: This study evaluated the accuracy of neonatal amplitude-integrated electroencephalography (aEEG) brain monitoring for predicting development of postneonatal epilepsy after perinatal hypoxic ischemic encephalopathy (HIE). METHODS: We studied a population-based cohort of 85 consecutive neonates with moderate-to-severe HIE that had aEEG started <12 hours postnatally. We marked electrographic seizures and graded each hour of the aEEG background as inactive, burst-suppression, or continuous without or with sleep cycling. These aEEG parameters were compared to outcome at 4-years age (deceased, epilepsy, cerebral palsy without epilepsy, favorable), which was available for 80 children. RESULTS: At group level, total seizure burden (p = 0.003), maximum hourly seizure burden (p = 0.007), and aEEG background recovery (p < 0.001) were all significantly associated with outcome. At individual level six children developed epilepsy, and the most accurate predictors for later epilepsy were inactive aEEG at 24 hours (accuracy 97%, positive predictive value 100%, two false negatives) and inactive aEEG at the onset of seizures (accuracy 97%, sensitivity of 100%, one false positive). CONCLUSIONS: At individual level aEEG background recovery was a better predictor for later epilepsy than neonatal seizures, although both were associated with epilepsy at group level. SIGNIFICANCE: Poor aEEG background recovery predicts development of epilepsy after perinatal HIE at individual level.

Somatosensory evoked potentials are abnormal with plagiocephaly.

BACKGROUND: Deformational plagiocephaly is usually managed conservatively, as it tends to improve over time and with the use of conservative measures. However, before the year 2017 we operated on patients with severe plagiocephaly and neurological symptoms at the Helsinki Cleft Palate and Craniofacial Center. METHODS: Of the 20 infants with severe deformational plagiocephaly and neurological symptoms referred to us between 2014 and 2016, 10 underwent cranioplasty open reshaping of the posterior cranial vault. The parents of the last 10 patients were given information on the natural history of the condition and the patients were followed up with an outpatient protocol. The aim of this study was to gain information on the brain electrophysiology and recovery of patients after total cranial vault reconstruction by measuring the electroencephalogram (EEG) somatosensory evoked potentials (SEP; median nerve). RESULTS: Of the 10 participants in the operation arm, six had abnormal SEP at least on the affected cerebral hemisphere and all SEPs were recorded as normal when controlled postoperatively. In the follow-up arm, eight out of 10 participants had abnormal SEP at the age of approximately 24 months, and all had normalized SEPs at control visits. CONCLUSION: Our data suggest that cranioplasty open reshaping of the posterior cranial vault did not affect abnormal SEP-EEG recordings. We have abandoned the operations in deformational plagiocephaly patients due to findings suggesting that expanding cranioplasty is not beneficial for brain function in this patient group.

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome.

PURPOSE: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. METHODS: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. RESULTS: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. CONCLUSION: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.

Detrended fluctuation analysis in the presurgical evaluation of parietal lobe epilepsy patients.

OBJECTIVE: To examine the usability of long-range temporal correlations (LRTCs) in non-invasive localization of the epileptogenic zone (EZ) in refractory parietal lobe epilepsy (RPLE) patients. METHODS: We analyzed 10 RPLE patients who had presurgical MEG and underwent epilepsy surgery. We quantified LRTCs with detrended fluctuation analysis (DFA) at four frequency bands for 200 cortical regions estimated using individual source models. We correlated individually the DFA maps to the distance from the resection area and from cortical locations of interictal epileptiform discharges (IEDs). Additionally, three clinical experts inspected the DFA maps to visually assess the most likely EZ locations. RESULTS: The DFA maps correlated with the distance to resection area in patients with type II focal cortical dysplasia (FCD) (p<0.05), but not in other etiologies. Similarly, the DFA maps correlated with the IED locations only in the FCD II patients. Visual analysis of the DFA maps showed high interobserver agreement and accuracy in FCD patients in assigning the affected hemisphere and lobe. CONCLUSIONS: Aberrant LRTCs correlate with the resection areas and IED locations. SIGNIFICANCE: This methodological pilot study demonstrates the feasibility of approximating cortical LRTCs from MEG that may aid in the EZ localization and provide new non-invasive insight into the presurgical evaluation of epilepsy.

Secondary somatosensory cortex evoked responses and 6-year neurodevelopmental outcome in extremely preterm children.

OBJECTIVE: We assessed in extremely preterm born (EPB) children whether secondary somatosensory cortex (SII) responses recorded with magnetoencephalography (MEG) at term-equivalent age (TEA) correlate with neurodevelopmental outcome at age 6 years. Secondly, we assessed whether SII responses differ between 6-year-old EPB and term-born (TB) children. METHODS: 39 EPB children underwent MEG with tactile stimulation at TEA. At age 6 years, 32 EPB and 26 TB children underwent MEG including a sensorimotor task requiring attention and motor inhibition. SII responses to tactile stimulation were modeled with equivalent current dipoles. Neurological outcome, motor competence, and general cognitive ability were prospectively evaluated at age 6 years. RESULTS: Unilaterally absent SII response at TEA was associated with abnormal motor competence in 6-year-old EPB children (p = 0.03). At age 6 years, SII responses were bilaterally detectable in most EPB (88%) and TB (92%) children (group comparison, p = 0.69). Motor inhibition was associated with decreased SII peak latencies in TB children, but EPB children lacked this effect (p = 0.02). CONCLUSIONS: Unilateral absence of an SII response at TEA predicted poorer motor outcome in EPB children. SIGNIFICANCE: Neurophysiological methods may provide new means for outcome prognostication in EPB children.

Early oxygen levels contribute to brain injury in extremely preterm infants.

BACKGROUND: Extremely low gestational age newborns (ELGANs) are at risk of neurodevelopmental impairments that may originate in early NICU care. We hypothesized that early oxygen saturations (SpO2), arterial pO2 levels, and supplemental oxygen (FiO2) would associate with later neuroanatomic changes. METHODS: SpO2, arterial blood gases, and FiO2 from 73 ELGANs (GA 26.4 ± 1.2; BW 867 ± 179 g) during the first 3 postnatal days were correlated with later white matter injury (WM, MRI, n = 69), secondary cortical somatosensory processing in magnetoencephalography (MEG-SII, n = 39), Hempel neurological examination (n = 66), and developmental quotients of Griffiths Mental Developmental Scales (GMDS, n = 58). RESULTS: The ELGANs with later WM abnormalities exhibited lower SpO2 and pO2 levels, and higher FiO2 need during the first 3 days than those with normal WM. They also had higher pCO2 values. The infants with abnormal MEG-SII showed opposite findings, i.e., displayed higher SpO2 and pO2 levels and lower FiO2 need, than those with better outcomes. Severe WM changes and abnormal MEG-SII were correlated with adverse neurodevelopment. CONCLUSIONS: Low oxygen levels and high FiO2 need during the NICU care associate with WM abnormalities, whereas higher oxygen levels correlate with abnormal MEG-SII. The results may indicate certain brain structures being more vulnerable to hypoxia and others to hyperoxia, thus emphasizing the role of strict saturation targets. IMPACT: This study indicates that both abnormally low and high oxygen levels during early NICU care are harmful for later neurodevelopmental outcomes in preterm neonates. Specific brain structures seem to be vulnerable to low and others to high oxygen levels. The findings may have clinical implications as oxygen is one of the most common therapies given in NICUs. The results emphasize the role of strict saturation targets during the early postnatal period in preterm infants.

Towards multimodal brain monitoring in asphyxiated newborns with amplitude-integrated EEG and simultaneous somatosensory evoked potentials.

BACKGROUND: Somatosensory evoked potentials (SEPs) offer an additional bedside tool for outcome prediction after perinatal asphyxia. AIMS: To assess the reliability of SEPs recorded with bifrontoparietal amplitude-integrated electroencephalography (aEEG) brain monitoring setup for outcome prediction in asphyxiated newborns undergoing therapeutic hypothermia. STUDY DESIGN: Retrospective observational single-center study. SUBJECTS: 27 consecutive asphyxiated full- or near-term newborns (25 under hypothermia) that underwent median nerve aEEG-SEPs as part of their clinical evaluation at the neonatal intensive care unit of Helsinki University Hospital. OUTCOME MEASURES: aEEG-SEP classification (present, absent or unreliable) was compared to classification of SEPs recorded with a full EEG montage (EEG-SEP), and outcome determined from medical records at approximately 12-months-age. Unfavorable outcome included death, cerebral palsy, or severe epilepsy. RESULTS: The aEEG-SEP and EEG-SEP classifications were concordant in 21 of the 22 newborns with both recordings available. All five newborns with bilaterally absent aEEG-SEPs had absent EEG-SEPs and the four with outcome information available had an unfavorable outcome (one was lost to follow-up). Of the newborns with aEEG-SEPs present, all with follow-up exams available had bilaterally present EEG-SEPs and a favorable outcome (one was lost to follow-up). One newborn with unilaterally absent aEEG-SEP at 25 h of age had bilaterally present EEG-SEPs on the next day, and a favorable outcome. CONCLUSIONS: aEEG-SEPs recorded during therapeutic hypothermia on the first postnatal days are reliable for assessing brain injury severity. Adding SEP into routine aEEG brain monitoring offers an additional tool for very early outcome prediction after birth asphyxia.

Neonatal neuroimaging and neurophysiology predict infantile onset epilepsy after perinatal hypoxic ischemic encephalopathy.

PURPOSE: To evaluate the accuracy of hypoxic ischemic encephalopathy (HIE) grade, and neonatal neurophysiological and neuroimaging measures for predicting development of infantile spasms syndrome (IS) or other postneonatal, infantile onset epilepsy after perinatal HIE. METHODS: We examined a population-based cohort of 92 consequent infants with moderate-to-severe HIE. The HIE grade and neonatal neuroimaging (MRI) and neurophysiology (EEG and somatosensory evoked potentials, SEPs) findings were compared to the development of IS or other epilepsy within the first year of life. RESULTS: Out of 74 surviving infants with follow-up information, five developed IS and one developed a focal onset epilepsy. They all had recovered from severe HIE. All survivors with inactive neonatal EEG (recorded within the first few postnatal days, n = 4) or the most severe type of brain injury in MRI (n = 3) developed epilepsy (positive predictive value, PPV 100 %). Bilaterally absent SEPs had 100 % sensitivity and 75 % PPV for epilepsy. A combination of absent SEPs and a poor MRI finding (combined deep and cortical gray matter injury) resulted in higher PPV (86 %) without lowering sensitivity (100 %). Follow-up EEGs showed recurrent epileptiform activity already between 1- and 2-months age in those that developed epilepsy, distinguishing them from those surviving without epilepsy. CONCLUSIONS: Poor neonatal neuroimaging and neurophysiological findings provide accurate prediction for development of infantile onset epilepsy after HIE. Of the neonates with severe HIE, the ones with severe neonatal MRI and neurophysiological abnormalities need frequent follow-up, including repeated EEGs, for early detection of IS.

Interictal magnetoencephalography in parietal lobe epilepsy - Comparison of equivalent current dipole and beamformer (SAMepi) analysis.

OBJECTIVE: To evaluate a novel analysis method (SAMepi) in the localization of interictal epileptiform magnetoencephalographic (MEG) activity in parietal lobe epilepsy (PLE) patients in comparison with equivalent current dipole (ECD) analysis. METHODS: We analyzed the preoperative interictal MEG of 17 operated PLE patients utilizing visual analysis and: (1) ECD with a spherical conductor model; (2) ECD with a boundary element method (BEM) conductor model; and (3) SAMepi - a kurtosis beamformer method. Localization results were compared between the three methods, to the location of the resection and to the clinical outcome. RESULTS: Fourteen patients had an epileptiform finding in the visual analysis; SAMepi detected spikes in 11 of them. A unifocal finding in both the ECD and in the SAMepi analysis was associated with a better chance of seizure-freedom (p = 0.02). There was no significant difference in the distances from the unifocal MEG localizations to the nearest border of the resection between the different analysis methods. CONCLUSIONS: Localizations of unifocal interictal spikes detected by SAMepi did not significantly differ from the conventional ECD localizations. SIGNIFICANCE: SAMepi - a novel semiautomatic analysis method - is useful in localizing interictal epileptiform MEG activity in the presurgical evaluation of parietal lobe epilepsy patients.

Anatomoelectroclinical features of SEEG-confirmed pure insular-onset epilepsy.

PURPOSE: In this study, we aimed to improve our knowledge of insular epilepsy by studying anatomoelectroclinical correlations in pure insular-onset epilepsy and characterizing differences between anterior and posterior insular-onset seizures. METHODS: Patients in whom seizure-onset zone was confined to the insula and peri-insular sulcus were selected from 301 consecutive presurgical stereo-electroencephalography (EEG) recordings performed between years 2010 and 2017 in two epilepsy centers. Ictal-onset zone in stereo-EEG was delineated visually and quantitatively using epileptogenic index method. Seizure characteristics were reanalyzed, and anatomoelectroclinical correlations were assessed. Characteristics of posterior and anterior insular-onset seizures were compared. RESULTS: Eleven insular cases were identified, five of them with an anterior insular seizure onset and six with a posterior one. Nonpainful somatosensory symptoms and autonomic symptoms were the most common symptoms (73% of patients) followed by speech-related symptoms (55%) and ipsilateral eye blinking (45%). Six patients had seizures restricted to somatosensory or viscerosensory symptoms. In all patients, seizures progressed to motor symptoms. Somatosensory symptoms did not differentiate anterior from posterior insular seizures. However, hyperkinetic signs, speech modifications, and viscerosensory symptoms were related to an anterior insular seizure-onset zone. Pain, asymmetric tonic, focal clonic, and tonic symptoms were more frequent in patients with a posterior insular seizure onset. CONCLUSIONS: Seizure semiology is heterogeneous in pure insular-onset epilepsy. Differences between the anterior and posterior insular seizures reflect the functional organization of the insula. Particularly, the different types of motor symptoms may help to distinguish anterior from posterior insular seizure onset.

Mid-Term Outcome after Selective Neurotization of the Infraspinatus Muscle in Patients with Brachial Plexus Birth Injury.

Active shoulder external rotation in adduction can be restored by selective neurotization of the infraspinatus muscle with the spinal accessory nerve in select patients with brachial plexus birth injury. Does the improved shoulder external rotation stand the test of time? METHODS: Fourteen consecutive brachial plexus birth injury patients with active shoulder external rotation in adduction of ≤ 0 degrees and active shoulder elevation ≥ 90 degrees underwent selective neurotization of the infraspinatus muscle at mean 2 years of age between 2012 and 2016. All 14 patients had congruent shoulders joints with passive external rotation in adduction of 30 degrees. Pre-and postoperative electromyography was done to seven patients. Shoulder function and the subjective outcome was assessed after a mean follow-up of 3.8 years. RESULTS: Shoulder external rotation in adduction improved by a mean 57 degrees in the 12 children who did not develop shoulder internal rotation contracture. Shoulder external rotation in abduction and shoulder abduction increased in all 14 patients. Reinnervation of the supraspinatus muscle was evident in all seven children who underwent postoperative EMG. Thirteen patients' parents were satisfied with the outcome. CONCLUSIONS: Functionally significant shoulder external rotation can be restored and maintained by reinnervation of the infraspinatus muscle in brachial plexus birth injury patients with congruent shoulder joints, if internal rotation contracture does not develop.

Bedside neurophysiological tests can identify neonates with stroke leading to cerebral palsy.

OBJECTIVE: The unspecific symptoms of neonatal stroke still challenge its bedside diagnosis. We studied the accuracy of routine electroencephalography (EEG) and simultaneously recorded somatosensory evoked potentials (EEG-SEP) for diagnosis and outcome prediction of neonatal stroke. METHODS: We evaluated EEG and EEG-SEPs from a hospital cohort of 174 near-term neonates with suspected seizures or encephalopathy, 32 of whom were diagnosed with acute ischemic or hemorrhagic stroke in MRI. EEG was scored for background activity and seizures. SEPs were classified as present or absent. Developmental outcome of stroke survivors was evaluated from medical records at 8- to 18-months age. RESULTS: The combination of continuous EEG and uni- or bilaterally absent SEP (n = 10) was exclusively seen in neonates with a middle cerebral artery (MCA) stroke (specificity 100%). Moreover, 80% of the neonates with this finding developed with cerebral palsy. Bilaterally present SEPs did not exclude stroke, but predicted favorable neuromotor outcome in stroke survivors (positive predictive value 95%). CONCLUSIONS: Absent SEP combined with continuous EEG background in near-term neonates indicates an MCA stroke and a high risk for cerebral palsy. SIGNIFICANCE: EEG-SEP offers a bedside method for diagnostic screening and a reliable prediction of neuromotor outcome in neonates suspected of having a stroke.