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ABSTRACT: Seizures occur more often during the neonatal period than at any other period of life. Precise incidence is difficult to delineate and depends on study population and criteria used for diagnosis of seizures. Controversy exists as to whether neonatal seizures themselves cause damage to the developing brain, or if the damage is primarily due to the underlying cause of the seizures. As a result of this controversy there is an ongoing discussion as to whether all seizures (both clinical and subclinical) should be treated. When (sub)clinical seizures are treated, there is no consensus about the most appropriate treatment for neonatal seizures and how to assess the efficacy of treatment. Current therapeutic options to treat neonatal seizures (i.e. primarily first generation antiepileptics) are relatively ineffective. There is an urgent need for prospective, randomized, controlled trials for efficacy and safety of these second-generation antiepileptic drugs in neonates. The aim of this review is to survey current knowledge regarding treatment of neonatal seizures in both term and preterm infants.
Seminars in Fetal and Neonatal Medicine 02/2013; · 3.91 Impact Factor
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ABSTRACT: Background:Sedative and analgesic medications are used in critically ill newborns, but little is known about their effects on electrocortical activity in preterm infants. We hypothesized that morphine might induce prolonged neurodepression, independent of blood pressure, compared with rapid sequence induction/intubation (RSI).Methods:Of 34 infants enrolled into a randomized controlled trial (RCT) comparing RSI (including thiopental 2-3 mg/kg and remifentantil 1 microg/kg) with morphine (0.3 mg/kg) as premedication for intubation, 28 infants (n=14+14; median gestational age 26.1 weeks and postnatal age 138 h) had continuous two-channel amplitude-integrated electroencephalogram (aEEG/EEG) and blood pressure monitoring during 24 h after the intubation. Thirteen infants not receiving any additional medication constituted the primary study group. Visual and quantitative analyses of aEEG/EEG and blood pressure were performed in 3-h epochs.Results:RSI was associated with aEEG/EEG depression lasting less than 3 h. Morphine premedication resulted in aEEG/EEG depression with more discontinuous background and less developed cyclicity for 24 h, and during the first 9 h interburst intervals were significantly increased compared to RSI. The difference was not related to blood pressure.Conclusion:Premedication with morphine is associated with prolonged aEEG/EEG depression independent of blood pressure changes, and may not be optimal for short procedures.Pediatric Research (2012); doi:10.1038/pr.2012.153.
Pediatric Research 11/2012; · 2.70 Impact Factor
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ABSTRACT: To characterize early amplitude-integrated electroencephalogram (aEEG) and single-channel EEG (aEEG/EEG) in very preterm (VPT) infants for prediction of long-term outcome.
Forty-nine infants with median (range) gestational age of 25 (22-30) weeks.
Amplitude-integrated electroencephalogram/EEG recorded during the first 72 h and analysed over 0-12, 12-24, 24-48 and 48-72 h, for background pattern, sleep-wake cycling, seizures, interburst intervals (IBI) and interburst percentage (IB%). In total, 2614 h of single-channel EEG examined for seizures. Survivors were assessed at 2 years corrected age with a neurological examination and Bayley Scales of Infant Development-II. Poor outcome was defined as death or survival with neurodevelopmental impairment. Good outcome was defined as survival without impairment.
Thirty infants had good outcome. Poor outcome (n = 19) was associated with depressed aEEG/EEG already during the first 12 h (p = 0.023), and with prolonged IBI and higher IB% at 24 h. Seizures were present in 43% of the infants and associated with intraventricular haemorrhages but not with outcome. Best predictors of poor outcome were burst-suppression pattern [76% correctly predicted; positive predictive value (PPV) 63%, negative predictive value (NPV) 91%], IBI > 6 sec (74% correctly predicted; PPV 67%, NPV 79%) and IB% > 55% at 24 h age (79% correctly predicted; PPV 72%, NPV 80%). In 35 infants with normal cerebral ultrasound during the first 3 days, outcome was correctly predicted in 82% by IB% (PPV 82%, NPV 83%).
Long-term outcome can be predicted by aEEG/EEG with 75-80% accuracy already at 24 postnatal hours in VPT infants, also in infants with no early indication of brain injury.
Acta Paediatrica 03/2012; 101(7):719-26. · 2.07 Impact Factor
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ABSTRACT: To compare rapid sequence intubation (RSI) premedication with morphine for intubation of preterm infants.
Preterm infants needing semi-urgent intubation were enrolled to either RSI (glycopyrrolate, thiopental, suxamethonium, and remifentanil, n = 17) or atropine and morphine (n = 17) in a randomized trial. The main outcome was "good intubation conditions" (score ≤10 assessed with intubation scoring), and secondary outcomes were procedural duration, physiological and biochemical variables, amplitude-integrated electroencephalogram, and pain scores.
Infants receiving RSI had superior intubation conditions (16/17 versus 1/17, P < .001), the median (IQR) intubation score was 5 (5-6) compared with 12 (10.0-13.5, P < .001), and a shorter procedure duration of 45 seconds (35-154) compared with 97 seconds (49-365, P = .031). The morphine group had prolonged heart rate decrease (area under the curve, P < .009) and mean arterial blood pressure increase (area under the curve, P < .005 and %change: mean ± SD 21% ± 23% versus -2% ± 22%, P < .007) during the intubation, and a subsequent lower mean arterial blood pressure 3 hours after the intubation compared with baseline (P = .033), concomitant with neurophysiologic depression (P < .001) for 6 hours after. Plasma cortisol and stress/pain scores were similar.
RSI with the drugs used can be implemented as medication for semi-urgent intubation in preterm infants. Because of circulatory changes and neurophysiological depression found during and after the intubation in infants given morphine, premedication with morphine should be avoided.
The Journal of pediatrics 07/2011; 159(6):893-9.e1. · 4.02 Impact Factor
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ABSTRACT: To investigate if Paco(2) and plasma glucose levels affect electrocortical activity.
Ours was an observational study of 32 infants with a gestational age of 22 to 27 weeks. We performed simultaneous single-channel electroencephalogram (EEG) and repeated blood gas/plasma glucose analyses during the first 3 days (n = 247 blood samples with corresponding EEG). Interburst intervals (IBIs) and EEG power were averaged at the time of each blood sample.
There was a linear relationship between Paco(2) and IBI; increasing Paco(2) was associated with longer IBIs. One day after birth, a 1-kPa increase in Paco(2) was associated with a 16% increase in IBI in infants who survived the first week without severe brain injury. EEG power was highest at a Paco(2) value of 5.1 kPa and was attenuated both at higher and lower Paco(2) values. Corrected for carbon dioxide effects, plasma glucose was also associated with IBI. Lowest IBI appeared at a plasma glucose level of 4.0 mmol/L, and there was a U-shaped relationship between plasma glucose level and EEG with increasing discontinuity at glucose concentrations above and below 4.0 mmol/L.
Both carbon dioxide and plasma glucose level influenced EEG activity in extremely preterm infants, and values considered to be within normal physiologic ranges were associated with the best EEG background. Increasing EEG discontinuity occurred at carbon dioxide levels frequently applied in lung-protection strategies; in addition, moderate hyperglycemia was associated with measurable EEG changes. The long-term effects of changes in carbon dioxide and glucose on brain function are not known.
PEDIATRICS 03/2011; 127(4):e1028-34. · 4.47 Impact Factor
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ABSTRACT: IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain.
The aim of this study was to evaluate the association between postnatal serum concentrations of IGF-I and IGFBP-3 and brain volumes at term in very preterm infants.
Fifty-one infants with a mean (sd) gestational age (GA) of 26.4 (1.9) wk and birth weight (BW) of 888 (288) g were studied, with weekly blood sampling of IGF-I and IGFBP-3 from birth until 35 gestational weeks (GW) and daily calculation of protein and caloric intake. Magnetic resonance images obtained at 40 GW were segmented into total brain, cerebellar, cerebrospinal fluid, gray matter, and unmyelinated white matter volumes.
We evaluated brain growth by measuring brain volumes using magnetic resonance imaging.
Mean IGF-I concentrations from birth to 35 GW correlated with total brain volume, unmyelinated white matter volume, gray matter volume, and cerebellar volume [r = 0.55 (P < 0.001); r = 0.55 (P < 0.001); r = 0.44 (P = 0.002); and r = 0.58 (P < 0.001), respectively]. Similar correlations were observed for IGFBP-3 concentrations. Correlations remained after adjustment for GA, mean protein and caloric intakes, gender, severe brain damage, and steroid treatment. Protein and caloric intakes were not related to brain volumes. Infants with BW small for GA had lower mean concentrations of IGF-I (P = 0.006) and smaller brain volumes (P = 0.001-0.013) than infants with BW appropriate for GA.
Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.
The Journal of clinical endocrinology and metabolism 02/2011; 96(4):1129-35. · 6.50 Impact Factor
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Lena Hellström-Westas
The Journal of pediatrics 11/2010; 157(5):700-1. · 4.02 Impact Factor
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ABSTRACT: We propose here a simple algorithm for automated detection of spontaneous activity transients (SATs) in early preterm electroencephalography (EEG). The parameters of the algorithm were optimized by supervised learning using a gold standard created from visual classification data obtained from three human raters. The generalization performance of the algorithm was estimated by leave-one-out cross-validation. The mean sensitivity of the optimized algorithm was 97% (range 91-100%) and specificity 95% (76-100%). The optimized algorithm makes it possible to systematically study brain state fluctuations of preterm infants.
Physiological Measurement 10/2010; 31(11):N85-93. · 1.68 Impact Factor
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ABSTRACT: To describe the characteristics of activity bursts in the early preterm EEG, to assess inter-rater agreement of burst detection by visual inspection, and to determine the performance of an automated burst detector that uses non-linear energy operator (NLEO).
EEG recordings from extremely preterm (n=12) and very preterm (n=6) infants were analysed. Three neurophysiologists independently marked bursts in the EEG, the characteristics of bursts were analyzed and inter-rater agreement determined. Unanimous detections were used as the gold standard in estimating the performance of an automated burst detector. In addition, some details of this automated detector were revised in an attempt to improve performance.
Overall, inter-rater agreement was 86% for extremely preterm infants and 81% for very preterm infants. In visual markings, bursts had variable lengths (approximately 1-10s) and increased amplitudes (and power) throughout the frequency spectrum. Accuracy of the original detection algorithm was 87% and 79% and accuracy of the revised algorithm 93% and 87% for extremely preterm and very preterm babies, respectively.
Visual detection of bursts from the early preterm EEG is comparable albeit not identical between raters. The original automated detector underestimates the amount of burst occurrence, but can be readily improved to yield results comparable to visual detection. Further clinical studies are warranted to assess the optimal descriptors of burst detection for monitoring and prognostication.
Validation of a burst detector offers an evidence-based platform for further development of brain monitors in very preterm babies.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 07/2010; 121(7):1015-22. · 3.12 Impact Factor
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ABSTRACT: Amplitude-integrated electroencephalogram (aEEG) at <6 hours is the best single outcome predictor in term infants with perinatal asphyxia at normothermia. Hypothermia has been used to treat those infants and proved to improve their outcome. The objectives of this study were to compare the predictive value of aEEG at <6 hours on outcomes in normothermia- and hypothermia-treated infants and to investigate the best outcome predictor (time to normal trace or sleep-wake cycling [SWC]) in normothermia- and hypothermia-treated infants.
Seventy-four infants were recruited by using the CoolCap entry criteria, and their outcomes were assessed by using the Bayley Scales of Infant Development II at 18 months. The aEEG was recorded for 72 hours. Patterns and voltages of aEEG backgrounds were assessed.
The positive predictive value of an abnormal aEEG pattern at the age of 3 to 6 hours was 84% for normothermia and 59% for hypothermia. Moderate abnormal voltage background at 3 to 6 hours of age did not predict outcome. The recovery time to normal background pattern was the best predictor of poor outcome (96.2% in hypothermia, 90.9% in normothermia). Never developing SWC always predicted poor outcome. Time to SWC was a better outcome predictor for infants who were treated with hypothermia (88.5%) than with normothermia (63.6%).
Early aEEG patterns can be used to predict outcome for infants treated with normothermia but not hypothermia. Infants with good outcome had normalized background pattern by 24 hours when treated with normothermia and by 48 hours when treated with hypothermia.
PEDIATRICS 07/2010; 126(1):e131-9. · 4.47 Impact Factor
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ABSTRACT: To compare cognitive ability, school achievement and self-perceived health aspects in adolescents born extremely preterm and term born controls.
Fifty-two, out of 61, extremely preterm born adolescents (mean age 18.4 years) and 54 matched controls (mean age 18.3 years) born at full term were investigated; intelligence quotient was measured with the Wechsler Adult Intelligence Scale; cognitive flexibility, i.e. a measure of visuomotor speed and attention, with the Trail Making Test; school achievement and choice of upper secondary programmes were reported. Health aspects were investigated in a semi structured interview.
The adolescents born prematurely had significantly lower IQ than the controls, mean 93 (SD 15.4) vs 106 (12.5), p < 0.001; showed slower visuomotor speed; had lower grades from compulsory school (192.7 vs 234.8, p < 0.001); and chose to a greater extent practical upper secondary school programmes. There were no differences between the groups in health care consumption, prevalence of chronic disease, allergy or infectious diseases.
Poorer cognitive performance, in extremely preterm born individuals, seems to persist into late adolescence. Fewer prematurely born than control chose theoretical upper secondary school programmes. However, no difference was noted regarding self-perceived health aspects.
Acta Paediatrica 05/2010; 99(9):1401-6. · 2.07 Impact Factor
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Epilepsia 06/2009; 50(5):1292-3. · 3.96 Impact Factor
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ABSTRACT: Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
To determine the 1-year survival in all infants born before 27 gestational weeks in Sweden during 2004-2007.
Population-based prospective observational study of extremely preterm infants (707 live-born and 304 stillbirths) born to 887 mothers in 904 deliveries (102 multiple births) in all obstetric and neonatal units in Sweden from April 1, 2004, to March 31, 2007.
Infant survival to 365 days and survival without major neonatal morbidity (intraventricular hemorrhage grade >2, retinopathy of prematurity stage >2, periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia). Associations between perinatal interventions and survival.
The incidence of extreme prematurity was 3.3 per 1000 infants. Overall perinatal mortality was 45% (from 93% at 22 weeks to 24% at 26 weeks), with 30% stillbirths, including 6.5% intrapartum deaths. Of live-born infants, 91% were admitted to neonatal intensive care and 70% survived to 1 year of age (95% confidence interval [CI], 67%-73%). The Kaplan-Meier survival estimates for 22, 23, 24, 25, and 26 weeks were 9.8% (95% CI, 4%-23%), 53% (95% CI, 44%-63%), 67% (95% CI, 59%-75%), 82% (95% CI, 76%-87%), and 85% (95% CI, 81%-90%), respectively. Lower risk of infant death was associated with tocolytic treatment (adjusted for gestational age odds ratio [OR], 0.43; 95% CI, 0.36-0.52), antenatal corticosteroids (OR, 0.44; 95% CI, 0.24-0.81), surfactant treatment within 2 hours after birth (OR, 0.47; 95% CI, 0.32-0.71), and birth at a level III hospital (OR, 0.49; 95% CI, 0.32-0.75). Among 1-year survivors, 45% had no major neonatal morbidity.
During 2004 to 2007, 1-year survival of infants born alive at 22 to 26 weeks of gestation in Sweden was 70% and ranged from 9.8% at 22 weeks to 85% at 26 weeks.
JAMA The Journal of the American Medical Association 06/2009; 301(21):2225-33. · 30.03 Impact Factor
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ABSTRACT: To investigate trends in mortality and morbidity in very preterm infants.
Population-based perinatal register; liveborn infants 22 + 0 to 31 + 6 gestational weeks were investigated (time period 1995-2004). Time trends for mortality and common morbidities were explored using logistic regression analyses.
Data from 1614 liveborn infants were included. There was an increase in live born infants below 25 gestational weeks, annual odds ratio (OR) 1.15 (95% CI: 1.08-1.23) and a decrease in mortality annual OR 0.82 (95% CI: 0.69-0.98). The rates of bronchopulmonary dysplasia (BPD) and sepsis increased during the study period, annual ORs of 1.10 (95% CI: 1.04-1.17) and 1.09 (95% CI: 1.03-1.16). The duration of mechanical ventilation increased for surviving infants <25 gestational weeks (p = 0.003), while the duration of continuous positive airway pressure (CPAP) increased for infants <28 gestational weeks (p = <0.001). There were no changes in the rates of intraventricular haemorrhages (IVH, 3-4), retinopathy of prematurity (ROP, 3-5), seizures or necrotizing enterocolitis (NEC).
During the 10-year period changes in mortality and morbidity were most pronounced for infants with GA <28 gestational weeks. The increasing rate of sepsis was present in infants <28 gestational weeks, whereas the increase in BPD was demonstrated in the whole study population <32 gestational weeks.
Acta Paediatrica 01/2009; 98(4):648-53. · 2.07 Impact Factor
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PEDIATRICS 11/2008; 122(4):863-5. · 4.47 Impact Factor
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ABSTRACT: To investigate if the early electroencephalogram (EEG) and amplitude-integrated EEG (aEEG) in very preterm infants is affected by perinatal inflammation and brain injury, and correlates with long-term outcome.
Sixteen infants born at 24-28 gestational weeks (median 25.5) had continuous EEG/aEEG during the first 72 h of life. Minimum and maximum EEG interburst intervals (IBI), and aEEG amplitudes were semi-automatically quantified and averaged over the recording period. Neonatal brain injury was diagnosed with repeated cranial ultrasound investigations. Nine cytokines from four time-points were analyzed during the first 72 h (umbilical cord blood, 6, 24 and 72 h), and outcome was assessed at 2 years of corrected age.
Infants with neonatal brain injury (n=9) had prolonged IBI, 11.8 (9.6-23.2) sec versus 8.2 (7.1-11.6) sec in infants (n=7) without brain damage (p=0.005). Handicap at 2 years (n=8, including two infants without neonatally diagnosed brain injury) was associated with prolonged neonatal IBI and lower aEEG amplitudes. Also aEEG amplitudes were decreased in infants with neonatal brain injury. There was a significant positive correlation between the averaged IBI and cord blood TNF-alpha (rs=0.595, p=0.025).
Early EEG depression is associated with increased cord blood TNF-alpha, neonatal brain damage and handicap at 2 years.
Acta Paediatrica 08/2008; 97(7):915-9. · 2.07 Impact Factor
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ABSTRACT: The current study aimed to characterize changes in EEG-related measures after noxious stimuli in neonates and to assess their potential utility as measures of pain and/or discomfort during neonatal intensive care. Seventy-two healthy term infants were investigated: Twenty-eight had a non-skin-breaking pin-prick on the heel, randomized to receive either oral glucose (n = 16) or water (n = 12) before the stimulus. Twenty-one infants were studied during a venous blood sample from the dorsum of the hand, 23 infants during a capillary heel stick. Behavioral pain responses were assessed with the Premature Infant Pain Profile Scale. The stimulus evoked a significant increase in higher frequency components (10-30 Hz) which also correlated to behavioral measures. The frontotemporal localization of the increased activity with frequency bands similar to electromuscular artifacts and the relation to behavioral measures confirmed that this activity corresponds to an increase in muscle tone. There was no change in frontal EEG asymmetry in any of the groups. The present results indicate that responses in cortical activity recorded by EEG are not useful for clinical assessment of infants' responses to noxious stimuli.
Pediatric Research 07/2008; 64(4):429-34. · 2.70 Impact Factor
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ABSTRACT: Outcome is uncertain in infants born at 23-24 gestational weeks. The aim of the present study was to identify possible early predictors of outcome in these infants.
Data from the Swedish medical birth register (MBR) for live-born infants with gestational ages (GAs) 23 and 24 weeks, born during the time-period 2000-2002, were analysed in relation to short-term outcomes, that is survival and survival without severe brain damage (intraventricular haemorrhage [IVH] grades 3 and 4 and/or periventricular leukomalacia [PVL]).
In 57 infants born at 23 gestational weeks, survival was associated with birthweight (BW) (p = 0.018) and 5-min Apgar score (p = 0.020) on univariate analyses. In 99 infants born at 24 weeks of gestation, survival without severe brain damage correlated with BW (p = 0.039), birth type (singleton/multiple) (p = 0.017) and Apgar score at 1, 5 and 10 min (p = 0.028, 0.014 and 0.030, respectively). The best model for predicting survival without severe brain damage in infants born at 24 gestational weeks was based on 5-min Apgar score and birth type. The small number of live-born infants at 23 weeks of gestation did not allow for multiple logistic regression analyses.
The 5-min Apgar score is associated with short-term outcome in live-born infants at 23-24 gestational weeks. The association is stronger for infants born at 24 weeks of gestation.
Acta Paediatrica 06/2008; 97(5):551-6. · 2.07 Impact Factor
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ABSTRACT: Screening examination for retinopathy of prematurity is distressing and painful. The aim of the present study was to investigate whether a Newborn Individualized Developmental Care and Assessment Program intervention during a retinopathy of prematurity examination results in less adverse behavioral, pain, and stress responses as compared with standard care.
The first 2 eye examinations in 36 preterm infants were evaluated. The infants were randomly assigned at the first eye examination to receive either Newborn Individualized Developmental Care and Assessment Program care or standard care. At the second examination, crossover of subject assignment was performed. The assessments included behavioral responses; recordings of heart rate, respiration, and oxygenation; pain scores (premature infant pain profile); and salivary cortisol at defined time points up to 4 hours after the eye examination. The nursing support given during the eye examinations (intervention score) were scored using predefined criteria.
Altogether, 68 examinations were evaluated. Newborn Individualized Developmental Care and Assessment Program care was associated with better behavioral scores during the examination but there was no difference in heart rate, respiratory rate, oxygenation, or premature infant pain profile score between the 2 care strategies before or after the eye examination. Salivary cortisol increased from baseline to 30 minutes after the eye examination independent of care strategy and decreased significantly between 30 and 60 minutes when infants were subjected to Newborn Individualized Developmental Care and Assessment Program care but not after standard care. During the study period the intervention score for standard care increased and approached the score for Newborn Individualized Developmental Care and Assessment Program care at the later eye examinations.
A Newborn Individualized Developmental Care and Assessment Program-based intervention during eye examination does not decrease pain responses but results in faster recovery, as measured by lower salivary cortisol 60 minutes after the examination. The differences were seen despite the influence from the Newborn Individualized Developmental Care and Assessment Program intervention on the standard care treatment that occurred during the study period.
PEDIATRICS 06/2008; 121(5):e1267-78. · 4.47 Impact Factor
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Lena Hellström-Westas
Nature Clinical Practice Neurology 03/2008; 4(2):74-5. · 7.64 Impact Factor
