Hans Forssberg

Karolinska Institutet, Сольна, Stockholm, Sweden

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Publications (180)635.98 Total impact

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    ABSTRACT: Poor growth and malnutrition are frequently reported in children with cerebral palsy in developed countries,but there is limited information from developing countries. We investigatedthe nutritional status of Ugandan children with cerebral palsy and described factors associated with poor nutrition. We examined135 children from two to 12yearswith cerebral palsy,who attended Uganda's national referral hospital. A child was considered underweight, wasted, stunted or thin if the standard deviation scores for their weight for age, weight for height, height for age and body mass index for age were ≤-2.0 using World Health Organization growth standards. Multivariable logistic regression identified factors associated with nutritional indicators. Over half (52%) of the children were malnourished, with underweight (42%) being the most common category, followed by stunting (38%), thinness (21%), and wasting (18%). Factors that were independently associated with being malnourished were: presence of cognitive impairment, with an adjusted odds ratio (aOR) of 4.5, being five years or older (aOR = 3.4) and feeding difficulties in the perinatal period (aOR = 3.2). Malnutrition was common in Ugandan children with cerebral palsy and more likely if they were fiveyears or more or had experienced neonatal complications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Acta Paediatrica 06/2015; DOI:10.1111/apa.13089 · 1.67 Impact Factor
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    ABSTRACT: To study whether a temporary block of the tactile afferents from the fingers causes altered activity in the neural network for dexterous manipulation. Whole-brain functional Magnetic Resonance Imaging (fMRI) was conducted in 18 healthy subjects, while they compressed an unstable spring between the thumb and index finger of the right hand. Two sensory conditions - with and without tactile input from the fingers - were employed. In the latter condition the digital nerves were blocked by local anesthesia. Compression of the unstable spring was associated with activity in an earlier described network for object manipulation. We found that this entire network remained active after a nerve block, and the activity was increased in the dorsal premotor cortex. The neural network for dexterous manipulation is robust with only minor alterations after acute loss of tactile information from the fingers. There was no loss of activity, but, unexpectedly, an increased activity in some parts of the network. This study gives new insights to possible neural compensatory mechanisms that make fine motor control possible after acute disruption of tactile information in natural situations like cold weather or wearing surgical gloves. Copyright © 2015. Published by Elsevier B.V.
    Brain research 05/2015; 1620. DOI:10.1016/j.brainres.2015.05.016 · 2.84 Impact Factor
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    ABSTRACT: Cerebral palsy (CP) is a common chronic childhood disorder worldwide. There is limited information about the CP panorama in sub-Saharan Africa. Our aim was to describe the clinical subtypes, gross and fine motor functions and presence of co-morbidities in a group of children with CP attending a tertiary hospital in Uganda. Children with CP in the age range of 2-12 years visiting the paediatric CP clinic at Mulago Hospital, Kampala, were enrolled. Screening and inclusion were based on a three-stage procedure: i) Two screening questions from the Ten Question Screen; ii) Clinical assessments adapted from the Surveillance for Cerebral Palsy in Europe (SCPE); iii) Clinical examinations and diagnoses of subtype, severity level and co-morbidities. Caregivers were interviewed using questionnaires to provide information on child's medical history and co-morbidities. Co-morbidity scores were calculated for each child. One hundred and thirty five children with CP were enrolled (72 males, 63 females, median age 3 years 5 months, IQR-2 years 4 months-5 years 6 months). Bilateral spastic type was commonest (45%); moderate impairment in gross motor function was present in 43%, with comparable numbers (37%) in the mild and severely impaired fine motor function groups. The severe gross and fine motor function levels were seen in the bilateral spastic and dyskinetic CP subtypes. Signs of learning disability (75%) and epilepsy (45%) were the commonest co-morbidities. Higher co-morbidity scores were obtained in children with dyskinetic CP and severe levels of gross and fine motor function. There was a significant difference in distribution of the co-morbidity scores between the CP subtypes, gross motor and fine motor function levels (p <0.001). Signs of speech and language impairments were associated with bilateral spastic CP and severe gross and fine motor dysfunction (p < 0.05). Bilateral spastic CP was the main clinical subtype, with signs of learning disability and epilepsy as major causes of co-morbidity. The severity of gross and fine motor function levels was related to severity of clinical CP subtypes. Our findings imply a higher occurrence of birth asphyxia or post natally acquired infections. Improvement in emergency obstetric and postnatal care may reduce this burden.
    BMC Research Notes 04/2015; 8(1):166. DOI:10.1186/s13104-015-1125-9
  • Carlton Chu · Hugo Lagercrantz · Hans Forssberg · Zoltan Nagy
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    ABSTRACT: Background and aims Preterm birth is identified as a risk factor for brain development. We investigate the utility of support vector machine classification as a biological marker for outcome after preterm birth. Methods We trained a linear support vector machine using the grey matter segment (Figure 2) of a 3D MR image (resolution 0.98 × 0.98 × 1.5 mm3) collected from 143 individuals (69 controls) at adolescence. Subsequently, each individual was automatically classified preterm/control. Using birth weight, gestational age or IQ as independent variables and the prediction score (i.e. distance to the decision boundary) as dependent variable we quantified correlations. Results Correct classifications occurred 93% of the time. The correlation with the prediction score was stronger for birth weight (R = –0.51, p < 0.000001) than gestational age (R = –0.24, p < 0.04) but wasn’t significant within the control group only. IQ was significantly correlated with the prediction score (R = –0.30, p < 0.001). Fig1 depicts the prediction scores for both groups (Top). For the subset for which it was available the IQ scores were used to colour code the scatter plot (bottom). Conclusions The 93% correct classification is comparable to studies involving individuals with e.g. Alzheimers. The current study is a proof-of-principle, testing the necessary condition whether SVM classification could identify individuals who were born preterm based on a single MR image. The long-term goal of this method is predicting outcome by classifying preterm individuals as having a more “control-like” or “preterm-like” brain. Such information could be used to predict neurological/psychological scores and outcome.
    PLoS ONE 04/2015; 10(4):e0123108. DOI:10.1371/journal.pone.0123108 · 3.23 Impact Factor
  • Rochellys Diaz Heijtz · Hans Forssberg
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    ABSTRACT: Cerebral palsy (CP) is a heterogeneous group of neurodevelopmental disorders associated with lifelong motor impairment and disability. Current intervention programmes aim to capitalize on the neuroplasticity of the undamaged part of the brain to improve motor functions, by engaging individuals in active motor learning and training. In this review, we highlight recent animal studies (1) exploring cellular and molecular mechanisms contributing to neuroplasticity during motor training, (2) assessing the functional role of the mesocortical dopaminergic system in motor skill learning, and (3) exploring the impact of naturally occurring genetic variation in dopamine-related gene expression on the acquisition and performance of fine motor skills. Finally, the potential influence of the dopamine system on the outcome of motor learning interventions in cerebral palsy is discussed. © 2015 The Authors. Developmental Medicine & Child Neurology © 2015 Mac Keith Press.
    Developmental Medicine & Child Neurology 04/2015; 57 Suppl 2(s2):10-4. DOI:10.1111/dmcn.12692 · 3.51 Impact Factor
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    ABSTRACT: AimThe aim of this study was to investigate long-term cognitive outcome in a cohort of 18-year-olds born preterm and previously assessed at the age of 5.5.Methods We tested 134 adolescents born preterm with a very low birthweight of <1500 g and 94 term-born controls with a comprehensive cognitive battery at 18 years of age. The cohort was subdivided into 73 extremely preterm, 42 very preterm and 19 moderately preterm infants with gestational ages of 23-27, 28-31 and 32-36 weeks, respectively. The moderately preterm group was dominated by adolescents born small for gestational age.ResultsVery preterm adolescents performed on a par with term-born controls. In contrast, extremely preterm adolescents displayed inferior results on all cognitive tests, more so if they had suffered neonatal complications. Moderately preterm adolescents scored lower than very preterm and full-term born adolescents, particularly on complex cognitive tasks.Conclusion Adolescents born at 28 weeks of gestation or later, with appropriate birthweight and no perinatal complications, functioned like term-born peers at 18 years of age. Extremely preterm birth per se posed a risk for long-term cognitive deficits, particularly executive deficits. Adolescents born moderately preterm but small for gestational age were at risk of general cognitive deficits.
    Acta paediatrica (Oslo, Norway: 1992). Supplement 11/2014; 104(3). DOI:10.1111/apa.12864
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    ABSTRACT: Cognitive outcome after preterm birth is heterogeneous, and group level analyses may disguise individual variability in development. Using a person-oriented approach, this study investigated individual cognitive patterns and developmental trajectories from preschool age to late adolescence. As part of a prospective longitudinal study, 118 adolescents born preterm, with a birth weight < 1,500 g, participated in neuropsychological assessments at age 5½ years and at 18 years. At each age, four cognitive indices, two tapping general ability and two tapping executive functions, were formed to reflect each individual's cognitive profile. Cluster analyses were performed at each age separately, and individual movements between clusters across time were investigated. At both 5½ and 18 years, six distinct, and similar, cognitive patterns were identified. Executive functions were a weakness for some but not all subgroups, and verbal ability was a strength primarily among those whose overall performance fell within the normal range. Overall, cognitive ability at 5½ years was highly predictive of ability at age 18. Those who performed at low levels at 5½ years did not catch up but rather deteriorated in relative performance. Over half of the individuals who performed above the norm at 5½ years improved their relative performance by age 18. Among those performing around the norm at 5½ years, half improved their relative performance over time, whereas the other half faced increased problems, indicating a need for further developmental monitoring. Perinatal factors were not conclusively related to outcome, stressing the need for cognitive follow-up assessment of the preterm-born child before school entry.
    Child Neuropsychology 09/2014; 21(5):1-20. DOI:10.1080/09297049.2014.958071 · 2.42 Impact Factor
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    ABSTRACT: Background and purpose: Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. Materials and methods: This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. Results: The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. Conclusions: Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury.
    American Journal of Neuroradiology 08/2014; 36(1). DOI:10.3174/ajnr.A4072 · 3.59 Impact Factor
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    ABSTRACT: Objective: The NeuroFlexor objectively quantifies the neural, elastic and viscous components of passive movement resistance in wrist and finger flexor muscles. In this study we investigated the sensitivity of the NeuroFlexor to changes in spasticity induced by treatment with botulinum toxin type A (BoNT-A). Design: Prospective observational design. Subjects: A convenience sample of 22 adults with post-stroke upper limb spasticity scheduled for botulinum toxin treatment. Methods: BoNT-A was given according to individual treatment plans. NeuroFlexor assessments were made before treatment and 4 and 12 weeks after. Results: At group level, spasticity decreased significantly at 4 weeks (expected time of maximum effect) (p = 0.04). At 12 weeks, spasticity had rebounded and no longer differed significantly from baseline (p = 0.64), i.e. in line with the pharmacodynamics of BoNT-A. At the individual level, 7 participants showed a reduction in spasticity greater than the measurement error. The reduction was dose-dependent (r(20) = 0.66, p < 0.001), and largest in participants with the highest dose. Conclusion: At the group level, the sensitivity of NeuroFlexor is good enough to detect reduction in spasticity after treatment with BoNT-A. Further work is needed to establish the sensitivity of NeuroFlexor on an individual level.
    Journal of Rehabilitation Medicine 05/2014; 46(7). DOI:10.2340/16501977-1824 · 1.68 Impact Factor
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    Journal of Foot and Ankle Research 04/2014; 7(Suppl 1):A87. DOI:10.1186/1757-1146-7-S1-A87 · 1.46 Impact Factor
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    Developmental Medicine & Child Neurology 04/2014; 56(4):398-400. DOI:10.1111/dmcn.12412 · 3.51 Impact Factor
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    ABSTRACT: First, we explore the performance of nonword repetition (NWR) in children with specific language impairment (SLI) and typically developing children (TD) in order to investigate the accuracy of NWR as a clinical marker for SLI in Swedish-speaking school-age children. Second, we examine the relationship between NWR, family aggregation, and parental level of education in children with SLI. A sample of 61 children with SLI, and 86 children with TD, aged 8-12 years, were administered an NWR test. Family aggregation, measured as the prevalence of language and/or literacy problems (LLP) in parents of the children with SLI, was based on family history interviews. The sensitivity and specificity of nonword repetition was analyzed in a binary logistic regression, cut-off values were established with ROC curves, and positive and negative likelihood ratios reported. Results from the present study show that NWR distinguishes well between Swedish-speaking school-children with and without SLI. We found 90.2% sensitivity and 97.7% specificity at a cut-off level of -2 standard deviations for binary scoring of nonwords. Differences between the SLI and TD groups showed large effect sizes for the two scoring measures binary (d = 2.11) and percent correct consonants (PCC) (d = 1.79). The children with SLI were split into two subgroups: those with no parents affected with LLP (n = 12), and those with one or both parents affected (n = 49). The subgroup consisting of affected parents had a significantly lower score on NWR binary (p = .037), and there was a great difference between the subgroups (d = 0.7). When compared to the TD group, the difference from the subgroup with affected parents was almost one standard deviation larger (d = 2.47) than the difference from the TD to the subgroup consisting of non-affected parents (d = 1.57). Our study calls for further exploration of the complex interaction between family aggregation, language input, and phenotypes of SLI.
    PLoS ONE 02/2014; 9(2):e89544. DOI:10.1371/journal.pone.0089544 · 3.23 Impact Factor
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    ABSTRACT: The aim of the study was to explore individual variations in outcome of hand function after constraint-induced movement therapy (CIMT) in relation to the organization of corticomotor projection and brain lesion characteristics in participants with unilateral cerebral palsy (CP). Sixteen participants (eight males, eight females; mean age 13y, [SD 2y] range 10-16y) with unilateral CP (nine right-sided; Manual Ability Classification System [MACS] level I, n=1; level II, n=15) who participated in a 2-week CIMT day camp (63h) were included in the study. Various aspects of hand function were measured by the Jebsen-Taylor Hand Function Test (JTHFT), the Assisting Hand Assessment (AHA), and the Melbourne Assessment, both before and after the day camp. Transcranial magnetic stimulation was used to explore the corticomotor organization, and brain lesion characteristics were described by visual assessment of conventional structural magnetic resonance images. At a group level, the training was associated with significant improvements in JTHFT (p=0.003) and AHA (p=0.046), but not in Melbourne Assessment scores. Improvements were found in all types of corticomotor projection patterns, i.e. contralateral, mixed, and ipsilateral. There was no relationship between functional improvement and brain lesion characteristics. Individuals with CP experience improved motor outcomes after CIMT, independent of corticomotor projection pattern and lesion characteristics.
    Developmental Medicine & Child Neurology 12/2013; 56(3). DOI:10.1111/dmcn.12353 · 3.51 Impact Factor
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    ABSTRACT: While it is clear that the development of dexterous manipulation in children exhibits dramatic improvements over an extended period, it is difficult to separate musculoskeletal from neural contributors to these important functional gains. This is in part due to the inability of current methods to disambiguate improvements in hand strength from gains in finger dexterity (i.e., the dynamic control of fingertip force vectors at low magnitudes). We adapted our novel instrumentation to evaluate finger dexterity in 130 typically developing children between the ages of 4 and 16. We find that finger dexterity continues to develop well into late adolescence; and musculoskeletal growth and strength are poorly correlated with the improvements in dexterity. Importantly, because these behavioral results seem to mirror the known timelines of neuroanatomical development up to adolescence, we speculate they reflect the functional benefits of such continual neural maturation. This novel perspective now enables the systematic study of the functional roles of specific neuroanatomical structures, their connectivity, maturity and plasticity. Moreover, the temporal dynamics of the fingertip force vectors shows improvements in stability that provide a novel way to look at the maturation of finger control. From a clinical perspective, our results provide a practical means to chart functional development of dexterous manipulation in typically developing children, and could be adapted for clinical use, and for use in children with developmental disorders.
    Journal of Neurophysiology 07/2013; 110(7). DOI:10.1152/jn.00320.2013 · 2.89 Impact Factor
  • Yu Qian · Meng Chen · Hans Forssberg · Rochellys Diaz Heijtz
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    ABSTRACT: Several neurodevelopmental disorders with a strong genetic basis, including attention-deficit/hyperactivity disorder, autism spectrum disorders and developmental coordination disorder, involve deficits in fine motor skills. This phenotype may depend on heritable variation in components of the dopamine system, which is known to play a critical role in motor skill learning. In the present study, we took advantage of two inbred strains of mice (BALB/c and C57BL/6) that differ markedly in the number of midbrain dopamine neurons, in order to investigate the influence of such naturally occurring genetic variation on the acquisition and performance of fine motor skills. Gene expression analysis of midbrain, frontal cortex, and striatum revealed significant differences in the expression of pre- and postsynaptic dopaminergic markers (e.g., tyrosine hydroxylase, dopamine transporter, dopamine D4 receptor, dopamine D5 receptor, and DARPP-32) between these two strains. BALB/c mice had lower learning rate and performance scores in a complex skilled reaching task when compared to C57BL/6 mice. A negative correlation was found between the motor learning rate and level of DARPP-32 mRNA expression in the frontal cortex contralateral to the trained forelimb. The rate of motor learning was also negatively correlated with the levels of DARPP-32 and dopamine D1 receptor mRNAs in the striatum. Our results suggest that genetically driven variation in fronto-striatal dopaminergic neurotransmission is a major contributor to individual differences in motor skill learning. Moreover, these findings implicate the D1R/cAMP/DARPP-32 signaling pathway in those neurodevelopmental disorders that are associated with fine motor skills deficits.
    Genes Brain and Behavior 07/2013; 12(6). DOI:10.1111/gbb.12062 · 3.66 Impact Factor
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    ABSTRACT: Objective: To describe the reliability of an instrument (Neuro- Flexor) designed to be used in the clinic for quantification of the relative contribution of spasticity, elasticity and viscosity to resistance during passive wrist movements. Design: A test-retest and inter-rater reliability study. Subjects: A convenience sample of 34 adults with chronic stroke with spasticity in the hand, and a reference group of 10 healthy persons. Methods: Two raters assessed the participants with the NeuroFlexor. Elastic, viscous and neural components of passive movement resistance were quantified at the wrist. Test-retest and inter-rater intraclass correlation coefficient (ICC2.1) were calculated for each component for both raters and two sessions. Degree of measurement error was evaluated using the coefficient of variation and the repeatability coefficient. Results: Reliability was high for the neural component (test-retest: 0.90-0.96; inter-rater: 0.90-0.94), fair to good for the elastic component (test-retest: 0.79-0.88; inter-rater: 0.76-0.76), and fair to high for the viscous component (test-retest: 0.88-0.90; inter-rater: 0.75-0.80). Based on test-retest data, the coefficients of variation for the neural, elastic and viscous components were 25%, 26% and 16%, respectively, and the repeatability coefficients were 1.798, 1.897 and 1.404, respectively. Conclusion: The NeuroFlexor instrument is a reliable measure of spasticity and of muscle elasticity and viscosity in individuals with wrist and finger muscle resistance to passive stretch after stroke.
    Journal of rehabilitation medicine: official journal of the UEMS European Board of Physical and Rehabilitation Medicine 05/2013; 45(7). DOI:10.2340/16501977-1160 · 1.68 Impact Factor
  • 2013 International Meeting for Autism Research; 05/2013
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    ABSTRACT: Objective: To investigate whether repeat courses of antenatal corticosteroids have long-term effects on cognitive and psychological functioning. Study design: In a prospective cohort study, 58 adolescents and young adults (36 males) who had been exposed to 2-9 weekly courses of betamethasone in utero were assessed with neuropsychological tests and behavior self-reports. Unexposed subjects (n = 44, 25 males) matched for age, sex, and gestational age at birth served as a comparison group. In addition, individuals exposed in utero to a single course (n = 25, 14 males) were included for dose-response analysis. Group differences were investigated using multilevel linear modeling. Results: Mean scores obtained in 2 measures of attention and speed were significantly lower in subjects exposed to 2 or more antenatal corticosteroids courses (Symbol Search, P = .009; Digit Span Forward, P = .02), but these were not dose-dependent. Exposure to repeat courses of antenatal corticosteroids was not associated with general deficits in higher cognitive functions, self-reported attention, adaptability, or overall psychological function. Conclusions: Although this study indicates that repeat exposure to antenatal corticosteroids may have an impact on aspects of executive functioning, it does not provide support for the prevailing concern that such fetal exposure will have a major adverse impact on cognitive functions and psychological health later in life.
    The Journal of pediatrics 02/2013; 163(2). DOI:10.1016/j.jpeds.2013.01.030 · 3.79 Impact Factor
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    Journal of Pediatrics 01/2013; · 3.79 Impact Factor
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    ABSTRACT: Background Preterm birth is associated with later hypertension and diabetes. One explanation for this association could be that exposure to antenatal corticosteroids (ACS), especially if repeated, induce adverse long-term effects. There are no data on whether repeat courses of ACS are associated with health problems later in life. The aim of this study was to assess whether repeat courses of ACS correlate to metabolic syndrome later in life. Methods In a population-based cohort we measured BMI, blood pressure, arterial stiffness, blood lipids and glucose tolerance in 58 subjects (36 boys, age 14 to 26 years) exposed to 2–9 weekly courses of antenatal betamethasone. Subjects exposed to a single course (n=25, 14 boys) and unexposed subjects (n=44, 25 boys) were included as comparison groups. Results As compared to unexposed controls, subjects exposed to repeat courses of ACS did not differ in BMI (mean difference 0.6kg/m2, p=0.5), mean systolic or diastolic blood pressure (mean diff 1mmHg, p=0.78–0.83), arterial stiffness assessed by pulse wave analysis (mean diff 0.1%, p=0.50), triglyceride (mean diff 0.1mmol/L), total cholesterol (mean diff 0mmol/L), LDL/HDL ratio (mean diff 0.1), Lipoprotein(a) (mean diff. 61mg/L), ApolipoproteinB/ApolipoproteinA1 ratio (mean diff 0.01), (p=0.33–0.91) or glucose tolerance assessed by HOMA-index (mean diff 0, p=0.84). Subjects exposed to a single course of ACS did not differ from the other groups in any of the variables above. Conclusions Repeat courses of ACS do not correlate to metabolic syndrome in young adulthood. This observation has clinical implications for the ongoing discussion about safety of antenatal steroids.
    Archives of Disease in Childhood 10/2012; 97(Suppl 2):A133-A133. DOI:10.1136/archdischild-2012-302724.0453 · 2.90 Impact Factor

Publication Stats

9k Citations
635.98 Total Impact Points


  • 1990–2015
    • Karolinska Institutet
      • Department of Women's and Children's Health
      Сольна, Stockholm, Sweden
  • 2013
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2003–2005
    • University of Groningen
      Groningen, Groningen, Netherlands
  • 2004
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 2001
    • Stockholm University
      Tukholma, Stockholm, Sweden
  • 1991–2001
    • Karolinska University Hospital
      • • Department of Pediatric Anesthesiology and Intensive Care
      • • Department of Neurology
      Tukholma, Stockholm, Sweden
    • University of Montana
      • Physical Therapy Department
      MSO, Montana, United States
  • 1996
    • University of Gothenburg
      Goeteborg, Västra Götaland, Sweden
  • 1982
    • Good Samaritan Hospital Medical Center
      Бей Шор, New York, United States