Neuro-imaging characteristics of sensory impairment in cerebral palsy; a systematic review.

Background: Objective: To identify and examine neural reorganization of the sensory network in terms of lesion type, somatotopic organization of the primary somatosensory area, and functional connectivity in relation to sensory function in children and young adults with cerebral palsy (CP). Methods: Design: systematic review, Prospero registration ID 342570. Data sources: PubMed; Cochrane; Web of Science; Embase; CINAHL and PEDro from inception to March 13, 2021. Eligibility criteria: All types of original studies, concerning sensory connectivity in relation to sensory outcome in patients with spastic CP, <30 years of age. No publication status or date restrictions were applied. Data extraction and synthesis: Two authors independently determined the eligibility of studies. Quality assessment was performed by a third author. Neuro-imaging/neurophysiological techniques, sensory outcomes and patient characteristics were extracted. Results: Children and young adults with periventricular leucomalacia (PVL) lesions have significantly better hand function and sensation scores than patients with cortical-subcortical/middle cerebral artery (MCA) lesions. Ipsilesional reorganization of the S1 (primary somatosensory cortex) area appears to be the primary compensation mechanism after a unilateral early brain lesion, regardless of the timing of the lesion. Interhemispheric reorganization of the sensory system after early brain lesions is rare and, when it occurs, poorly effective. Diffusion tractography shows a positive correlation between the ascending sensory tract (AST) diffusivity metrics of the more affected hemisphere and sensory test outcomes. Discussion and conclusions: Because of the large variability in study design, patient characteristics, neuroimaging/neurophysiological techniques and parameters as well as sensory assessment methods used, it is difficult to draw definite inferences on the relationship between the reorganization of the sensory network following early brain damage and sensory function in children and young adults with CP. In general, sensory function seems to be worse in cortical as opposed to white matter tract (PVL) lesions. International consensus on a clinically relevant sensory test battery is needed to enhance understanding of the intriguing compensatory mechanisms of sensory network following early brain damage and potential consequences for rehabilitation strategies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/.

Lower limb muscle fatigue after uphill walking in children with unilateral spastic cerebral palsy.

Fatigue during walking is a common complaint in cerebral palsy (CP). The primary purpose of this study is to investigate muscle fatigue from surface electromyography (sEMG) measurements after a treadmill-based fatigue protocol with increasing incline and speed in children with CP with drop foot. The secondary purpose is to investigate whether changes in sagittal kinematics of hip, knee and ankle occur after fatigue. Eighteen subjects with unilateral spastic CP performed the protocol while wearing their ankle-foot orthosis and scored their fatigue on the OMNI scale of perceived exertion. The median frequency (MF) and root mean square (RMS) were used as sEMG measures for fatigue and linear mixed effects model were applied. The MF was significantly decreased in fatigued condition, especially in the affected leg and in the tibialis anterior and peroneus longus muscle. The RMS did not change significantly in fatigued condition, while the OMNI fatigue score indicated patients felt really fatigued. No changes in sagittal kinematics of hip, knee and ankle were found using statistical non-parametric mapping. In conclusion, the current fatigue protocol seems promising in inducing fatigue in a population with CP with drop foot and it could be used to expand knowledge on muscle fatigue during walking in CP.

Additional value of advanced neurosonography and magnetic resonance imaging in fetuses at risk for brain damage.

OBJECTIVE: To assess the additional value of fetal multiplanar (axial, coronal and sagittal) neurosonography and magnetic resonance imaging (MRI) to that of the standard axial ultrasound planes in diagnosing brain damage in fetuses at high risk. METHODS: This was a prospective, multicenter, observational study. Women were eligible for participation if their fetus was at risk for acquired brain anomalies. Risk factors were congenital infection, alloimmune thrombocytopenia, fetal growth restriction, trauma during pregnancy, fetal hydrops, monochorionic twins and prior ultrasound finding suggestive of an acquired brain anomaly. Examinations of the fetal brain before birth comprised axial ultrasound and advanced neurosonography biweekly and MRI once. After birth, neonatal cranial ultrasound was performed at < 24 h and at term-equivalent age. Neonatal brain MRI was performed once at term-equivalent age. An expert panel blinded to medical information, including imaging findings by the other methods, evaluated the presence of periventricular echogenicity (PVE) changes, peri- and intraventricular hemorrhage (IVH) and changes in basal ganglia and/or thalami echogenicity (BGTE) on ultrasound, and the equivalent signal intensity (SI) changes on MRI. Conclusions on imaging findings were generated by consensus. The children were followed up with examinations for psychomotor development at 1 year of age, using the Touwen examination and Alberta Infant Motor Scale, and at 2 years of age using Bayley Scale of Infant Development-III (BSID-III) and behavioral, sensory profile and linguistic questionnaires; scores > 1 SD below the mean were considered suspicious for neurodevelopmental sequelae. RESULTS: Fifty-six fetuses were examined, and in 39/56 fetuses, all fetal-imaging modalities were available. PVE/SI changes were observed in 6/39, 21/39 and 2/39 fetuses on axial ultrasound planes, multiplanar neurosonography and MRI, respectively. IVH was found in 3/39, 11/39 and 1/39 fetuses, and BGTE/SI changes in 0/39, 12/39 and 0/39 fetuses, respectively. Outcome was suspicious for neurodevelopmental sequelae in 13/46 infants at 1 year, and at 2 years, 41/41 children had scores within 1 SD of the mean on BSID-III and 20 had scores > 1 SD below the mean on the behavioral (5/38), sensory profile (17/37) and/or linguistic (6/39) questionnaires. CONCLUSIONS: In this cohort of fetuses at risk for brain damage, the severity of acquired brain anomalies was limited. Nevertheless, multiplanar neurosonography detected more fetal PVE changes, IVH and/or BGTE changes compared to the standard axial ultrasound planes and MRI. Fetal MRI did not demonstrate any anomalies that were not seen on neurosonography. Neurodevelopmental outcome at 2 years of age showed no or mild impairment in most cases. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Mobility Characteristics of Children with Spastic Paraplegia Due to a Mutation in the KIF1A Gene.

Several de novo variants in the KIF1A gene have been reported to cause a complicated form of hereditary spastic paraplegia. Additional symptoms include cognitive impairment and varying degrees of peripheral neuropathy, epilepsy, decreased visual acuity, and ataxia. We describe four patients (ages 10-18 years), focusing on their mobility and gait characteristics. Two patients were not able to walk without assistance and showed a severe abnormal gait pattern, crouch gait. At examination, severe contractures were found.In addition to describing the different phenotypes with specific attention to gait in our cases, we reviewed known KIF1A mutations and summarized their associated phenotypes.We conclude that mobility and cognition are severely affected in children with spastic paraplegia due to de novo KIF1A mutations. Deterioration in mobility is most likely due to progressive spasticity, muscle weakness, and the secondary development of severe contractures, possibly combined with an additional progressive polyneuropathy. Close follow-up and treatment of these patients are warranted.

Neurodevelopmental outcome at 2 years of age in preterm infants with late-onset sepsis.

Late-onset sepsis is associated with impaired neurodevelopmental outcome in preterm infants. This prospective cohort study aims to establish the effect of sepsis after 72 h of life on cognitive, psychomotor, and language development of preterm infants (below 32 weeks gestational age and/or below 1500 g). At 2 years corrected age, neurodevelopmental outcome was tested using Bayley's Scales of Infant Development-II, Lexilijst (lexical development questionnaire), and behavior checklists. Of 117 patients included, 85 experienced blood culture-proven infection. Coagulase-negative staphylococci were responsible for 55% of the episodes. No significant differences were found in cognitive, motor, and behavioral scores or lexiquotient comparing patients with versus no proven infection. When comparing three groups (coagulase-negative staphylococci, other, and negative blood culture), a significant difference was found in composite cognitive scores (p = 0.016), in favor of the coagulase-negative staphylococci group versus other causal agent group (p = 0.007). No significant differences were found in other subscales.Conclusion: In this cohort, no differences were found in neurodevelopmental outcome at 2 years corrected age between proven and no proven infection groups; confirmation in larger cohorts with a control group is needed. Patients encountering coagulase-negative staphylococci sepsis showed a significant better cognitive outcome compared to other causal agents. What is Known: • Late-onset sepsis is associated with impaired neurodevelopmental outcome in preterm infants. What is New: • Preterm infants encountering late-onset sepsis by coagulase-negative staphylococci show a better cognitive outcome in comparison to other causal infectious agents in this cohort. • No differences were found in neurodevelopment at 2 years of age in preterm infants with suspected lateonset sepsis, between proven and no proven infection groups. Confirmation is needed in larger cohorts with a substantial control group.

Placental Histology After Minor Trauma in Pregnancy: A Pilot Study.

OBJECTIVE: Trauma in pregnancy may cause placental abruption. Consequences of moderate placental injury on neurodevelopment are unknown. The aim was to evaluate placental histology after maternal trauma. METHODS: A prospective study was conducted at 2 tertiary medical centers in the Netherlands. Placentas from women exposed to maternal trauma ≥ 20 weeks' gestational age were histologically examined. Neurological follow-up of the infants was performed at 1 year of age by means of Alberta Infant Motor Scale. Histological findings were compared to placentas from pregnancies without trauma. PRINCIPAL RESULTS: Thirteen placentas were investigated in the trauma group. The control group consisted of 15 placentas. Placental pathology was seen more often in the trauma cases (11 of the 13) than in the controls (6 of the 15), P = .024. Neurological follow-up was normal. CONCLUSIONS: In this small population, majority of the placentas showed pathology after minor trauma in pregnancy without consequences for neurodevelopment at 1 year.

Neurobehavioural outcome in 6-18 year old children after trauma in pregnancy: Case-control study.

BACKGROUND: Maternal trauma complicates pregnancy in approximately 7%. Long-term development of children exposed to maternal trauma is unknown. AIM: To determine neurobehavioural outcome of children (6-18 years) born after maternal trauma in pregnancy compared to a matched control group. STUDY DESIGN: Case-control study performed at a tertiary medical centre. SUBJECTS: All consecutive children born after maternal hospitalization for trauma during pregnancy between 1995 and 2005. Controls were children born at the same hospital and period after an uneventful pregnancy. OUTCOME MEASURES: Trauma type and severity (Injury Severity Score, ≥9: severe); information from medical files at admission (cases). All mothers filled out two questionnaires about the infant; 1. concerning health, motor development and educational level, 2. concerning behavioural development through the validated Dutch version of the Child Behavior Checklist (CBCL). RESULTS: Questionnaires were returned by 34 cases and 28 controls. The traumas concerned mainly motor vehicle accidents and falls, and 3/34 had severe injuries. No differences in health, motor development, educational level and CBCL was found between the cases and controls, except for more hospitalization in the cases (p = 0.009). CONCLUSION: Long-term follow-up of a limited population of children 6-18 years after exposure of mainly non-severe trauma before birth is similar to a control population except for unexplained more hospitalization in the cases.

Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study.

INTRODUCTION: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. METHODS: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. RESULTS: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28-84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). CONCLUSION: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted.

European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch.

BACKGROUND AND PURPOSE: To support clinical decision-making in central neurological disorders, a physical examination is used to assess responses to passive muscle stretch. However, what exactly is being assessed is expressed and interpreted in different ways. A clear diagnostic framework is lacking. Therefore, the aim was to arrive at unambiguous terminology about the concepts and measurement around pathophysiological neuromuscular response to passive muscle stretch. METHODS: During two consensus meetings, 37 experts from 12 European countries filled online questionnaires based on a Delphi approach, followed by plenary discussion after rounds. Consensus was reached for agreement ≥75%. RESULTS: The term hyper-resistance should be used to describe the phenomenon of impaired neuromuscular response during passive stretch, instead of for example 'spasticity' or 'hypertonia'. From there, it is essential to distinguish non-neural (tissue-related) from neural (central nervous system related) contributions to hyper-resistance. Tissue contributions are elasticity, viscosity and muscle shortening. Neural contributions are velocity dependent stretch hyperreflexia and non-velocity dependent involuntary background activation. The term 'spasticity' should only be used next to stretch hyperreflexia, and 'stiffness' next to passive tissue contributions. When joint angle, moment and electromyography are recorded, components of hyper-resistance within the framework can be quantitatively assessed. CONCLUSIONS: A conceptual framework of pathophysiological responses to passive muscle stretch is defined. This framework can be used in clinical assessment of hyper-resistance and will improve communication between clinicians. Components within the framework are defined by objective parameters from instrumented assessment. These parameters need experimental validation in order to develop treatment algorithms based on the aetiology of the clinical phenomena.

Cerebral ultrasound abnormalities in preterm infants caused by late-onset sepsis.

INTRODUCTION: This study describes cerebral ultrasound abnormalities caused by late-onset sepsis (LOS) in very preterm infants with a gestational age of < 32 weeks and/or birthweight < 1500 grams. METHODS: The prospective study ("INFANT study") included 117 preterm infants with suspected LOS. Proven LOS was defined as a positive blood culture after 72 hours of life. In case of coagulase-negative staphylococci an elevated C-reactive protein was additionally required to establish proven LOS. Patients were identified as proven LOS and patients with only clinical symptoms of LOS. Cerebral ultrasound images were obtained in the first week after birth, during/after LOS and before discharge. Cerebral findings were divided in no/minor and major abnormalities. RESULTS: Eighty-six preterm infants had proven LOS and 31 preterm infants had only clinical signs of LOS. Four infants were excluded because pre-existing major brain abnormalities. No significant differences (p = 0.624) for incidence of major brain abnormalities on cerebral ultrasound were found. CONCLUSION: No differences were revealed in prevalence of major brain abnormalities between the groups with proven LOS and with clinical signs of LOS. Both infants with a gram negative sepsis developed major brain abnormalities, whereas only two of 66 preterm infants coagulase-negative staphylococci sepsis developed major brain abnormalities.

Effect of selective dorsal rhizotomy on daily care and comfort in non-walking children and adolescents with severe spasticity.

BACKGROUND: In non-walking children with severe spasticity, daily care can be difficult and many patients suffer from pain. Selective dorsal rhizotomy (SDR) reduces spasticity in the legs, and therefore has the potential to improve daily care and comfort. AIM: To examine effects of SDR on daily care and comfort in non-walking children with severe spasticity due to different underlying neurological conditions. METHODS: Medical history, changes in daily care and comfort and satisfaction with outcome were assessed retrospectively in non-walking children who underwent SDR in our center, with a mean follow-up of 1y 7m (range 11m-4y 3m). All eligible patients (n = 24, years 2009-2014) were included. RESULTS: Mean age at SDR was 12y 4m (SD 4y 3m, range 2y 8m-19y 3m). Associated orthopaedic problems were frequent. Seven patients underwent scoliosis correction in the same session. Most improvements were reported in dressing (n = 16), washing (n = 12) and comfort (n = 10). Median score for satisfaction was 7 on a scale of 10 (range 1-9). SDR resulted in reduction of spasticity in leg muscles. In nine patients dystonia was recorded post-operatively, mainly in children with congenital malformations and syndromes. INTERPRETATION: SDR is a single event intervention that can improve daily care and comfort in non-walking children with severe spasticity, and can safely be combined with scoliosis correction. Despite the improvements, satisfaction is variable. Careful attention is necessary for risk factors for dystonia, which may be unmasked after SDR.

Comparison of psychomotor outcome in patients with perinatal asphyxia with versus without therapeutic hypothermia at 4 years using the Ages and Stages Questionnaire screening tool.

INTRODUCTION: Therapeutic hypothermia improves outcome after perinatal asphyxia. The Ages and Stages Questionnaire is a screening tool to detect neurodevelopmental delay. In this study we examined the outcome of patients with perinatal asphyxia (defined as Apgar score <5 at 10 min, or continued need for resuscitation, or pH < 7.00 in umbilical cord or within one hour after birth) with and without therapeutic hypothermia treatment at the age of four years. METHODS: Cohort study of patients with perinatal asphyxia admitted to the Neonatal Intensive Care Units of the VU University Medical Center, Amsterdam and the Wilhelmina Children's Hospital, Utrecht in the year 2008. Parents were asked to fill out the 48 months Ages and Stages Questionnaire (ASQ). In Wilhelmina Children's Hospital treatment with therapeutic hypothermia was implemented in 2008, in the VU University Medical Center in 2009, providing a historical cohort. RESULTS/DISCUSSION: Twenty-three questionnaires were evaluated. Response rate of questionnaires for the VU Medical Center was 63% (n = 10) and Wilhelmina's Childrens Hospital 93% (n = 13). No significant differences were found in the mean scores between both groups. However, the untreated group scored more frequently under the -2 SD threshold. In the fine motor skills domain the difference was statistically significant (p = 0.031). In the treated group no patients developed cerebral palsy and in the untreated group two patients developed cerebral palsy. CONCLUSION: In this study patients treated with hypothermia tend to have a better neurodevelopmental outcome. No significant differences were found between the two groups, apart from the fine motor skills.

Feedback learning and behavior problems after pediatric traumatic brain injury.

BACKGROUND: Feedback learning is essential for behavioral development. We investigated feedback learning in relation to behavior problems after pediatric traumatic brain injury (TBI). METHOD: Children aged 6-13 years diagnosed with TBI (n = 112; 1.7 years post-injury) were compared with children with traumatic control (TC) injury (n = 52). TBI severity was defined as mild TBI without risk factors for complicated TBI (mildRF- TBI, n = 24), mild TBI with ⩾1 risk factor for complicated TBI (mildRF+ TBI, n = 51) and moderate/severe TBI (n = 37). The Probabilistic Learning Test was used to measure feedback learning, assessing the effects of inconsistent feedback on learning and generalization of learning from the learning context to novel contexts. The relation between feedback learning and behavioral functioning rated by parents and teachers was explored. RESULTS: No evidence was found for an effect of TBI on learning from inconsistent feedback, while the moderate/severe TBI group showed impaired generalization of learning from the learning context to novel contexts (p = 0.03, d = -0.51). Furthermore, the mildRF+ TBI and moderate/severe TBI groups had higher parent and teacher ratings of internalizing problems (p's ⩽ 0.04, d's ⩾ 0.47) than the TC group, while the moderate/severe TBI group also had higher parent ratings of externalizing problems (p = 0.006, d = 0.58). Importantly, poorer generalization of learning predicted higher parent ratings of externalizing problems in children with TBI (p = 0.03, ß = -0.21) and had diagnostic utility for the identification of children with TBI and clinically significant externalizing behavior problems (area under the curve = 0.77, p = 0.001). CONCLUSIONS: Moderate/severe pediatric TBI has a negative impact on generalization of learning, which may contribute to post-injury externalizing problems.

Pediatric neurocysticercosis: three cases presented in the Netherlands with divergent clinical presentations.

BACKGROUND: Neurocysticercosis is a helminthic disease that affects the central nervous system by the larvae of the Taenia solium, the pork tapeworm. Because of the growing number of immigrants from endemic areas, its incidence is increasing in Western Europe. CASES: We describe three children, aged between 2 and 13 years, two of whom have a definite and one a probable diagnosis of neurocysticercosis based on the "Del Brutto criteria." They presented with different symptoms and signs: symptomatic epilepsy, asymmetric cerebral palsy, and headache. Serological evaluation was negative in two of the three cases. All cases showed comparable abnormalities on magnetic resonance imaging of the brain: solitary or multiple, cystic lesions, with surrounding edema. In one of them, the "scolex" (part of the larvae) could be visualized. One case was treated with albendazole, the other two cases did not receive medication. CONCLUSION: A prompt diagnosis of neurocysticercosis by recognition of its typical brain lesions is important to prevent unnecessary diagnostic tests and treatment.

Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders.

Epilepsy and mental retardation limited to females (EFMR), caused by PCDH19 mutations, has a variable clinical expression that needs further exploration. Onset of epilepsy may be provoked by fever and can resemble Dravet syndrome. Furthermore, transmitting males have no seizures, but are reported to have rigid personalities suggesting possible autism spectrum disorders (ASD). Therefore, this study aimed to determine the phenotypic spectrum associated with PCDH19 mutations in Dravet-like and EFMR female patients and in males with ASD. We screened 120 females suffering from Dravet-like epilepsy, 136 females with EFMR features and 20 males with ASD. Phenotypes and genotypes of the PCDH19 mutation carriers were compared with those of 125 females with EFMR reported in the literature. We report 15 additional patients with a PCDH19 mutation. Review of clinical data of all reported patients showed that the clinical picture of EFMR is heterogeneous, but epilepsy onset in infancy, fever sensitivity and occurrence of seizures in clusters are key features. Seizures remit in the majority of patients during teenage years. Intellectual disability and behavioural disturbances are common. Fifty percent of all mutations are missense mutations, located in the extracellular domains only. Truncating mutations have been identified in all protein domains. One ASD proband carried one missense mutation predicted to have a deleterious effect, suggesting that ASD in males can be associated with PCDH19 mutations.

Incidence of acquired demyelinating syndromes of the CNS in Dutch children: a nationwide study.

Acquired demyelinating syndromes (ADS) can be a first presentation of multiple sclerosis (MS) in children. The incidence of these disorders in Europe is currently unknown. Children (<18 years old) living in the Netherlands who presented with ADS were included from January 1, 2007 to December 31, 2010 by the Dutch pediatric MS study group and the Dutch surveillance of rare pediatric disorders. Demographic and clinical data were collected. Eighty-six patients were identified over 4 years, resulting in an incidence of 0.66/1,00,000 per year. Most patients presented with polyfocal ADS without encephalopathy (30%), followed by polyfocal ADS with encephalopathy (24%), optic neuritis (ON, 22%), monofocal ADS (16%), transverse myelitis (3%), and neuromyelitis optica (3%). Patients with polyfocal ADS with encephalopathy were younger (median 3.9 years) than patients with ON (median 14.6 years, p < 0.001) or monofocal ADS (median 16.0 years, p < 0.001). Patients with polyfocal ADS without encephalopathy (median 9.2 years) were also younger than monofocal ADS patients (median 16.0 years, p < 0.001). There was a slight female preponderance in all groups except the ON group, and a relatively large number of ADS patients (29%) reported a non-European ancestry. Familial autoimmune diseases were reported in 23%, more often in patients with relapsing disease than monophasic disease (46 vs. 15%, p = 0.002) and occurring most often in the maternal family (84%, p < 0.001). During the study period, 23% of patients were subsequently diagnosed with MS. The annual incidence of ADS in the Netherlands is 0.66/1,00,000 children/year. A polyfocal disease onset of ADS was most common.

Gaze behaviour during interception in children with spastic unilateral cerebral palsy.

Anticipatory gaze behaviour during interceptive movements was investigated in children with Spastic Unilateral Cerebral Palsy (SUCP), and related to the side of the intracerebral lesion. Five children with lesions of the right hemisphere (RHL) and five children with lesions of the left hemisphere (LHL) had to walk towards and intercept a ball that moved perpendicular to the walking path. Interception accuracy and gaze patterns were measured in a no-occlusion and occlusion condition, in which the ball was occluded from view for half of its trajectory. There was a clear support for a relationship between gaze behaviour and success in interception performance, with some evidence for the presence of anticipatory gaze behaviour. There were also differences in gaze behaviour between children with RHL and children with LHL that might be related to planning, but these did not affect interception accuracy. It is concluded that gaze behaviour during interceptive movements is anticipatory, and at least partly dependent on the lesional side.

Familial hemophagocytic lymphohistiocytosis in a pediatric patient diagnosed by brain magnetic resonance imaging.

Familial hemophagocytic lymphohistiocytosis (fHLH) is an autosomal recessive disorder characterized by proliferation and infiltration of several organs by activated lymphocytes and macrophages. Without allogeneic stem cell transplantation, fHLH is fatal. We describe a previously healthy 11-month-old boy with a rapidly progressive encephalopathy. An older brother died at 8 months following a subacute encephalopathy diagnosed as meningoencephalitis. The family history led to the suspicion of a metabolic disease, but metabolic studies were unrevealing. MRI showed multiple inhomogeneous signal abnormalities in the cortex and white matter, most prominent in the cerebral hemispheres and around the dentate nucleus. Gadolinium-enhanced T1-weighted images showed a multitude of enhancing foci, suggestive of perivascular enhancement. Based on MRI pattern with multiple lesions, perivascular enhancement and family history, fHLH was suspected. DNA analysis showed that the patient was compound-heterozygous for the c.445 G>A (p.Gly149Ser) mutation in exon 1 and the c.757 G>A (p.Glu253Lys) mutation in exon 2 of the perforin 1 gene. The patient was treated according to the international HLH-2004 protocol (dexamethasone, etoposide, cyclosporine, intrathecal methotrexate and prednisolone) followed by allogeneic cord blood transplantation. He showed a significant neurological and radiological improvement. The reported case demonstrates that MRI pattern recognition can lead to early diagnosis of fHLH, with subsequent adequate treatment.