Perioperative risk factors for long-term intelligence in children with postoperative cerebellar mutism syndrome after medulloblastoma surgery.

OBJECTIVE: Approximately 7%-50% of children with medulloblastoma (MB) develop postoperative cerebellar mutism syndrome (pCMS). pCMS has a short-term negative impact on intelligence, but effects on long-term outcomes are contradictory. The aim of this study was to assess long-term effects of pCMS in MB patients on aspects of intelligence quotient (IQ) and its perioperative risk factors. METHODS: In this single-center retrospective cohort study, 31 children were included (14 pCMS). Perioperative risk factors included brainstem invasion, vermis incision, hydrocephalus, tumor size, severity of pCMS, neurological symptoms, mean body temperature (BT) on days 1-4 post surgery, and age at resection. Age-appropriate Wechsler Intelligence tests were assessed at least 2 years after tumor resection. RESULTS: Mean interval between tumor resection and neuropsychological evaluation was 3.9 years in pCMS and 4 years and 11 months in the no-pCMS group. No significant differences in IQ scores were found between groups. The pCMS group had a clinically relevant difference of 10 points when compared to age norms on verbal IQ (VIQ). Bilateral pyramidal and swallowing problems were risk factors for lower performance. In the overall group, tumor size, younger age at surgery, and raised mean BT were negatively correlated with aspects of IQ. CONCLUSIONS: We found a clinically significant reduction of VIQ in the pCMS patient group. pCMS patients with a larger tumor size, younger age at surgery, a higher mean BT in the first days after surgery, bilateral pyramidal symptoms, and swallowing problems 10 days post surgery are more at risk for VIQ deficits at long-term.

Timing and Cause of Death in Children Following Return of Circulation After Out-of-Hospital Cardiac Arrest: A Single-Center Retrospective Cohort Study.

OBJECTIVES: To determine timing and cause of death in children admitted to the PICU following return of circulation after out-of-hospital cardiac arrest. DESIGN: Retrospective observational study. SETTING: Single-center observational cohort study at the PICU of a tertiary-care hospital (Erasmus MC-Sophia, Rotterdam, The Netherlands) between 2012 and 2017. PATIENTS: Children younger than 18 years old with out-of-hospital cardiac arrest and return of circulation admitted to the PICU. MEASUREMENTS AND RESULTS: Data included general, cardiopulmonary resuscitation and postreturn of circulation characteristics. The primary outcome was defined as survival to hospital discharge. Modes of death were classified as brain death, withdrawal of life-sustaining therapies due to poor neurologic prognosis, withdrawal of life-sustaining therapies due to refractory circulatory and/or respiratory failure, and recurrent cardiac arrest without return of circulation. One hundred thirteen children with out-of-hospital cardiac arrest were admitted to the PICU following return of circulation (median age 53 months, 64% male, most common cause of out-of-hospital cardiac arrest drowning [21%]). In these 113 children, there was 44% survival to hospital discharge and 56% nonsurvival to hospital discharge (brain death 29%, withdrawal of life-sustaining therapies due to poor neurologic prognosis 67%, withdrawal of life-sustaining therapies due to refractory circulatory and/or respiratory failure 2%, and recurrent cardiac arrest 2%). Compared with nonsurvivors, more survivors had witnessed arrest (p = 0.007), initial shockable rhythm (p < 0.001), shorter cardiopulmonary resuscitation duration (p < 0.001), and more favorable clinical neurologic examination within 24 hours after admission. Basic cardiopulmonary resuscitation event and postreturn of circulation (except for the number of extracorporeal membrane oxygenation) characteristics did not significantly differ between the withdrawal of life-sustaining therapies due to poor neurologic prognosis and brain death patients. Timing of decision-making to withdrawal of life-sustaining therapies due to poor neurologic prognosis ranged from 0 to 18 days (median: 0 d; interquartile range, 0-3) after cardiopulmonary resuscitation. The decision to withdrawal of life-sustaining therapies was based on neurologic examination (100%), electroencephalography (44%), and/or brain imaging (35%). CONCLUSIONS: More than half of children who achieve return of circulation after out-of-hospital cardiac arrest died after PICU admission. Of these deaths, two thirds (67%) underwent withdrawal of life-sustaining therapies based on an expected poor neurologic prognosis and did so early after return of circulation. There is a need for international guidelines for accurate neuroprognostication in children after cardiac arrest.

Effectiveness of the Brains Ahead! Intervention: 6 Months Results of a Randomized Controlled Trial in School-Aged Children With Mild Traumatic Brain Injury.

OBJECTIVE: To examine the effectiveness of Brains Ahead!, a psychoeducational intervention aimed to prevent long-term problems with activities and participation in children after mild traumatic brain injury (mTBI). PARTICIPANTS: In total, 124 children, aged 6 to 18 years, diagnosed with mTBI and their caregivers. METHOD: After randomization, participants in the intervention group received a face-to-face psychoeducational session with written take-home information and follow-up telephone call(s). Participants in the control group received usual care, consisting of a concise information brochure. PRIMARY OUTCOME MEASURES: Activities and participation (Child and Adolescent Scale of Participation [CASP]). SECONDARY OUTCOMES: fatigue, postconcussive symptoms (PCSs), posttraumatic stress symptoms (PTSSs), and quality of life (QOL). RESULTS: Generalized Estimated Equation analyses showed that both groups improved over the first 6 months post-mTBI, but the intervention group did not differ significantly on the CASP. Mann-Whitney U tests showed that the intervention group reported significantly less fatigue, PCSs, and PTSSs and better QOL compared with the control group at 6 months post-MTBI. CONCLUSIONS: The Brains Ahead! intervention resulted in significant improvements compared with usual care in reducing fatigue, PCSs, and PTSSs and improving QOL. Lack of an effect on activities and participation may be due to the ceiling effect of the CASP.

Activities and Participation in the First 6 Months After Mild Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: To investigate the natural course of activities and participation of children up to 6 months after a mild traumatic brain injury (mTBI). METHODS: A prospective longitudinal cohort study with complete data sets of 231 children diagnosed with mTBI and their caregivers. MAIN MEASURES: Activities and participation assessed with the Child and Adolescent Scale of Participation (CASP) and the Children's Assessment of Participation and Enjoyment (CAPE) measured at 2 weeks, 3 months, and 6 months post-mTBI. Because of a ceiling effect, the primary outcome measure (CASP) was divided into deviant (not maximum score) or full functioning. RESULTS: Friedman's, Cochran's Q, and McNemar's tests (CASP) and repeated-measures analyses of variance (CAPE) showed significant increases in activities and participation between 2 weeks and 3 and 6 months after mTBI. Based on the parents' perspective, 67% of the children returned to full functioning at 6 months postinjury, with only 38% of the children describing themselves as functioning at their premorbid level. DISCUSSION: Findings indicate that most children return to maximum level of activities and participation over time after mTBI. In a substantial number of children, however, the level of activities and participation at 6 months postinjury is evaluated as lower than that of peers. The importance of investigating predictors for child and caregiver perspectives is emphasized.

Process evaluation of 'Brains Ahead!': an intervention for children and adolescents with mild traumatic brain injury within a randomized controlled trial.

OBJECTIVE: To investigate whether the 'Brains Ahead! Intervention for children and adolescents with mild traumatic brain injury' was implemented as intended. In addition, involvement in and satisfaction with the intervention among patients, caregivers and professionals delivering the intervention were studied. DESIGN: Mixed methods, prospective study. PARTICIPANTS: Children with mild traumatic brain injury and their caregivers, allocated to the intervention group of the randomized controlled trial in the 'Brains Ahead!' study, and the two professionals providing the intervention. INTERVENTION: The intervention consists of a standardized and individualized psychoeducational session with written take-home information, and follow-up telephone call(s). MAIN MEASURES: Registration forms, evaluation questionnaires for patients and caregivers and semi-structured interviews for professionals. DATA ANALYSIS: Qualitative data were categorized based on content. Quantitative data were reported as descriptive statistics. RESULTS: Fifty-five patients and caregivers out of 60 study-participants attended both sessions. All elements of the intervention were delivered to 53 study-participants. Evaluation questionnaires were completed by 21 of the 31 patients aged 12 years and older, and by 41 caregivers. Overall, the sessions were considered useful by 19 patients, 40 caregivers and both professionals. Reassurance, creating a better understanding and recognition of symptoms were rated as important aspects. On a scale from 1 to 10, the intervention was rated by children, caregivers and professionals with 7.6 (SD 1.2), 8.1 (SD .9) and 8.0 (SD .0), respectively. CONCLUSION: The 'Brains Ahead!' intervention was largely implemented as intended and the process evaluation revealed that it is considered feasible according to patients, caregivers and professionals.

Post-operative cerebellar mutism syndrome: rehabilitation issues.

INTRODUCTION: Tumors of the cerebellum are the most common brain tumors in children. Modern treatment and aggressive surgery have improved the overall survival. Consequently, growing numbers of survivors are at high risk for developing adverse and long-term neurological deficits including deficits of cognition, behavior, speech, and language. Post-operative cerebellar mutism syndrome (pCMS) is a well-known and frequently occurring complication of cerebellar tumor surgery in children. In the acute stage, children with pCMS may show deterioration of cerebellar motor function as well as pyramidal and cranial neuropathies. Most debilitating is the mutism or the severe reduction of speech and a range of neurobehavioral symptoms that may occur. In the long term, children that recover from pCMS continue to have more motor, behavioral, and cognitive problems than children who did not develop pCMS after cerebellar tumor surgery. The severity of these long-term sequelae seems to be related to the length of the mute phase. AIM OF THIS NARRATIVE REVIEW: The impact of pCMS on patients and families cannot be overstated. This contribution aims to discuss the present knowledge on the natural course, recovery, and rehabilitation of children with pCMS. We suggest future priorities in developing rehabilitation programs in order to improve the long-term quality of life and participation of children after cerebellar tumor surgery and after pCMS in particular.

Ketogenic diet treatment in recurrent diffuse intrinsic pontine glioma in children: A safety and feasibility study.

BACKGROUND: The mean overall survival rate of children with diffuse intrinsic pontine glioma (DIPG) is 9-11 months, with current standard treatment with fractionated radiotherapy and adjuvant chemotherapy. So far, novel therapeutic strategies have not yet resulted in significantly better survival. The main source of energy for glioblastoma cells is glucose. Therefore, metabolic alterations induced by the use of the extremely carbohydrate-restricted ketogenic diet (KD) as adjuvant therapy are subject of interest in cancer research. PROCEDURE: This study explores the safety and feasibility of the KD in children with recurrent DIPG and no remaining treatment options. Safety was defined as the number of adverse effects. Feasibility was defined as the number of patients who were able to use the KD for three months. Coping of patients and parents was measured with questionnaires. RESULTS: Three of 14 children referred to our hospital between 2010 and 2015 were included. Two patients completed the study, and one died before the end of the study. Hospitalizations were needed for placing a nasogastric tube (n = 1) and epileptic seizures (n = 1). Adverse effects related to the diet were mild and transient. Parents were highly motivated during the study. CONCLUSION: Use of KD is safe and feasible, but the effect on survival has to be proven in a larger cohort of children who start the KD earlier after diagnosis, preferably as adjuvant therapy to fractionated radiotherapy.

Fatigue and physical functioning in children with multiple sclerosis and acute disseminated encephalomyelitis.

BACKGROUND AND OBJECTIVE: Fatigue and physical impairments are a major concern in children with multiple sclerosis (MS) and after acute disseminated encephalomyelitis (post-ADEM). We here aimed to evaluate the interaction between fatigue, exercise capacity, motor performance, neurological status, and quality of life (HRQoL). METHODS: In this cross-sectional study, data of 38 children (MS n = 22, post-ADEM n = 16), aged 4-17 years attending our national pediatric MS center, were studied. Fatigue was measured with the Pediatric Quality of Life Multidimensional Fatigue Scale, exercise capacity with the Bruce Protocol, motor performance with the Movement Assessment Battery for Children second edition, HRQoL with the Pediatric Quality of Life Questionnaire, and extent of disability with the Expanded Disability Status Scale (EDSS). RESULTS: Children with MS and post-ADEM experienced more fatigue ( p < 0.001), reduced exercise capacity ( p < 0.001), and impaired motor performance ( p < 0.001), despite low scores on the EDSS. Fatigue, but not the other parameters, was significantly correlated with HRQoL. Fatigue was not correlated with exercise capacity. CONCLUSION: We confirm the major impact of fatigue on quality of life in children with MS and post-ADEM. Fatigue was not explained by reduced exercise capacity or impaired motor performance. An important finding for clinical practice is that the low EDSS score did not reflect the poor physical functioning.

T-cell activation marker sCD27 is associated with clinically definite multiple sclerosis in childhood-acquired demyelinating syndromes.

BACKGROUND: Cerebrospinal fluid (CSF) levels of T-cell activation marker soluble CD27 (sCD27) are associated with subsequent disease activity after a first attack of suspected MS in adults. The predictive value for disease course in children with acquired demyelinating syndromes (ADS) is unknown. OBJECTIVES: To assess the predictive value of sCD27 levels for clinically definite multiple sclerosis (CDMS) diagnosis in childhood ADS. METHODS: Children <18 years with a first demyelinating event were prospectively included and followed. Soluble CD27 was determined in CSF using an enzyme-linked immunosorbent assay (ELISA). Cox regression analyses were used to calculate hazard ratios (HRs) for CDMS. RESULTS: A total of 94 ADS children were included (ADS with encephalopathy (ADS+) n = 33 and ADS without encephalopathy (ADS-) n = 61). Of the 61 ADS- children, 21 (48%) were diagnosed with CDMS during follow-up. At baseline, sCD27 levels were higher in patients with a future CDMS diagnosis ( n = 29) than in monophasic ADS+ ( n = 30), monophasic ADS- ( n = 28) and relapsing non-MS patients ( n = 7; p < 0.001). In ADS- patients, sCD27 was associated with CDMS (HR = 1.8 per 100 U/mL increase in sCD27 levels, p = 0.031), after adjustments for age, oligoclonal bands and the presence of dissemination in space on baseline magnetic resonance imaging (MRI). CONCLUSION: CSF sCD27 levels at first attack of demyelination were associated with CDMS diagnosis in children. This makes sCD27 a potential clinically relevant quantitative marker when performing routine CSF diagnostics.

The Brains Ahead! intervention for children and adolescents with mild traumatic brain injury and their caregivers: rationale and description of the treatment protocol.

PURPOSE:: Approximately 20% of the children and adolescents after mild traumatic brain injury will not fully recover. They suffer long-term postconcussive symptoms and may experience limitations in activities and participation. Research suggests that early psychoeducational interventions may prevent long-term postconcussive symptoms. The Brains Ahead! intervention was developed to prevent long-term symptoms and, furthermore, to establish a more successful return to activities and participation after mild traumatic brain injury in children and adolescents. The intervention is currently being evaluated in a multicenter randomized controlled trial. RATIONALE:: Providing individualized information and personal advice in addition to standardized information about the injury and possible consequences early after the injury may enable patients and caregivers to recognize and anticipate on relevant symptoms at an early stage and to prevent problems in activities and participation. THEORY INTO PRACTICE:: The Brains Ahead! intervention is a psychoeducational intervention for children and adolescents who sustained a mild traumatic brain injury and for their caregivers. The patients will receive a partially standardized and partially individualized psychoeducational session and a telephone follow-up within the first two to eight weeks after the injury.

Evaluation of management and guideline adherence in children with mild traumatic brain injury.

AIM: To evaluate the management and guideline adherence in children with mild traumatic brain injury (MTBI) in emergency departments (ED) in the Netherlands. METHODS: A multicentre cohort study was conducted, including children younger than 18 years with MTBI who presented within 24 hours after trauma in the ED of hospitals in the southwest region of the Netherlands, in 2014. Primary outcome measures for management were percentages of performed computed tomography (CT) scans and hospital admissions. Guideline adherence was defined as percentages of correctly following the guideline. Secondary outcome measures were differences in management and guideline adherence between hospitals. RESULTS: About 563 patients were analysed. Hospital admission was the most frequently performed management type (49.2% hospital admission vs. 30.9% CT). In only 49.7% of patients, the guideline was followed correctly. A substantial overuse of hospital admission (35%) and underuse of CT (40.1%) were found. Percentages of hospital admission and CT varied between 39.4-55.6% and 23.3-44.1%, respectively, across hospitals. Percentages of correctly following the guideline varied between 39.2-64.9% across hospitals. CONCLUSION: These findings suggest that physicians in the participating hospitals prefer hospital admission of children with MTBI instead of CT despite the current recommendations of the national MTBI guideline in the Netherlands.

Cerebellar mutism syndrome: cause and rehabilitation.

PURPOSE OF REVIEW: Mutism of cerebellar origin may occur in the context of various causes but is most frequent in children after resection of a large midline cerebellar tumour. In this review, the endeavour to reach a consensus on name and definition of postoperative mutism of cerebellar origin and associated symptoms is highlighted. In addition, progress in understanding of cause and risk factors for the syndrome is discussed as well as the rehabilitation issues. RECENT FINDINGS: Consensus on the term cerebellar mutism syndrome (CMS) has been reached. The exact pathogenesis of CMS remains unclear. Recently, attention was drawn to the hypothesis that thermal injury might be an important mechanism in the pathogenesis of CMS. Diffusion tensor imaging tractography was found to visualize the damage to relevant pathways that are associated with persistent impairments after recovery of CMS. There is still no established treatment for CMS to date. SUMMARY: By reaching a consensus on terminology and description of CMS, a firm basis has been created for future research. The pathogenesis of CMS seems multifactorial and important risk factors have been found. However, CMS cannot be effectively prevented yet and no established or specific treatment is available, apart from very general rehabilitation and cognitive interventions.

The structural connectome of children with traumatic brain injury.

This study aimed to investigate the impact of mild to severe pediatric TBI on the structural connectome. Children aged 8-14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mildRF+ , n = 20) or moderate/severe TBI (n = 16) at 2.8 years post-injury. Probabilistic tractography on diffusion tensor imaging data was used in combination with graph theory to study structural connectivity. Functional outcome was measured using neurocognitive tests and parent and teacher questionnaires for behavioral functioning. The results revealed no evidence for an impact of mildRF+ TBI on the structural connectome. In contrast, the moderate/severe TBI group showed longer characteristic path length (P = 0.022, d = 0.82) than the TC group. Furthermore, longer characteristic path length was related to poorer intelligence and poorer working memory in children with TBI. In conclusion, children have abnormal organization of the structural connectome after moderate/severe TBI, which may be implicated in neurocognitive dysfunction associated with pediatric TBI. These findings should be interpreted in the context of our exploratory analyses, which indicate that the definition and weighting of connectivity (e.g., streamline density, fractional anisotropy) influence the properties of the reconstructed connectome and its sensitivity to the impact and outcome of pediatric TBI. Hum Brain Mapp 38:3603-3614, 2017. © 2017 Wiley Periodicals, Inc.

Development of emotional and behavioral problems in neurofibromatosis type 1 during young childhood.

This retrospective longitudinal study in young children with neurofibromatosis type 1 (NF1) aimed to identify if, and how early problems in behavior, intelligence, and language development are associated with later behavioral problems. At the first assessment at preschool age, we evaluated language skills, intelligence, and emotional and behavioral problems as reported by parents. The second assessment at school-age we evaluated intelligence, and emotional and behavioral problems as reported by parents and teachers. Association of baseline assessments with secondary assessment was evaluated using multivariable linear regression analysis. Of the 61 patients (25 males, 36 females; mean age 4;5 years [SD 1;1 years]) with NF1 who had a first assessment, 38 children (21 males, 17 females; mean age 7;11 years [SD 2;1 years]) had a second assessment after a mean period of 3;5 years. Longitudinal data on behavioral problems were collected for 23 of these children. Intelligence and language development were not associated with internalizing problems. Parent-rated internalizing behavioral problems significantly increased with age in this subgroup. Baseline internalizing problems predicted later internalizing problems (adjusted R2 = 0.33, p = 0.003). The presence of these problems at pre-school age may be predictive of internalizing problems at a later age.

Motor nerve excitability after childhood Guillain-Barré syndrome.

Residual motor nerve dysfunction after pediatric Guillain-Barré syndrome (GBS) was determined in an observational cross-sectional cohort study in patients who previously developed GBS during childhood (<18 years). Ulnar motor nerve dysfunction was defined by compound motor action potential (CMAP) scan in patients after a follow up of at least 1 year compared with age-matched healthy controls, in relation to clinical course and outcome. A total of 37 persons previously diagnosed with GBS in childhood were included with a mean age at current examination of 20.6 years (4-39 years). The median time between diagnosis and follow-up was 11 years (range: 1-22 years). CMAP scanning indicated ulnar motor nerve dysfunction in 25 (68%) participants. The most frequent abnormality was a reduction in nerve excitability observed both in those with residual limb weakness and in the majority of those with complete recovery. CMAP scan characteristics were not related to prognostic factors or outcome. In conclusion, GBS in childhood results in residual motor nerve excitability disturbances, even in those completely recovered, probably reflecting altered physiology of regenerated peripheral nerves.

Neurogenic lower urinary tract dysfunction in the early disease phase of paediatric multiple sclerosis.

Neurogenic lower urinary tract dysfunction (LUTD) in multiple sclerosis (MS) is highly prevalent in adults, but has not previously been described in paediatric MS. A total of 24 consecutive children with newly diagnosed MS were prospectively assessed for bladder and bowel problems early after diagnosis. Five of 24 children (21%) showed LUTD during assessment. One of these patients did not report voiding complaints. This high prevalence of LUTD indicates that all recently diagnosed patients with paediatric MS should be evaluated early in their disease and treated for urinary problems in order to prevent potential damage to the upper urinary tract.

Health-related quality of life and emotional problems in children surviving brain tumor treatment: A descriptive study of 2 cohorts.

The survival of childhood brain tumors has improved in the past 30 years, but acquired brain injury due to damage caused by tumor invasion and side effects of different treatment modalities frequently occurs. This study focused on residual impairments, health-related quality of life (HRQoL), and emotional and behavioral problems in 2 cohorts of survivors diagnosed and treated for various types of brain tumors. Survivors in the 2004 cohort visited the Erasmus Medical Centre for standardized follow-up between 2003 and 2004, and in the 2014 cohort, between 2012 and 2014. Data of neurologically impairments of all children were extracted from medical records. Parents and survivors filled out questionnaires on quality of life and emotional and behavioral problems. In both cohorts, approximately 55% of the survivors displayed neurologic impairments. In comparison with the healthy reference group, a reduced parent-reported quality of life was found on the Motor, Cognition, and Autonomy (Cohort 2004) scales. Comparison between the cohorts showed that parents in the 2004 cohort reported a higher HRQoL on the Motor and Cognitive functioning scales. In the 2014 cohort, children reported less negative emotions than healthy children. No increase in emotional or behavioral problems were reported by children in both cohorts, whereas parents reported problems in social functioning and isolation related to a delay in emotional development. Children surviving brain tumor treatment have a reduced quality of life. The authors therefore recommend regular screening of HRQoL and emotional and behavioral problems and referral to specific aftercare.

Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort.

BACKGROUND: Acquired demyelinating syndromes (ADS) in children are a group of distinct first immune-mediated demyelinating events of the central nervous system (CNS). Predictive biomarkers for future diagnosis are lacking. A putative target antigen is myelin oligodendrocyte glycoprotein (MOG). We analyzed the presence of MOG antibodies in a cohort of ADS patients in The Netherlands. METHODS: Using a cell-based assay, we analyzed 117 children with ADS from a nationwide cohort, whom were divided into five groups: optic neuritis (ON; n = 20), transverse myelitis (TM; n = 7), other monofocal ADS (n = 22), polyfocal ADS without encephalopathy (n = 44) and polyfocal ADS with encephalopathy (n = 24). Additionally, we tested children with other neurological diseases (OND; n = 13), healthy children (n = 31) and adult polyfocal ADS plus encephalopathy (ADEM) patients (n = 29). RESULTS: We found that 21 of the 117 children with ADS tested anti-MOG seropositive (18%). The group of patients with ADEM had the highest prevalence of anti-MOG seropositivity (42% versus 18% in the non-encephalopathic polyfocal ADS patients). Although 47 ADS children had a final diagnosis of multiple sclerosis (MS), in only one of them were MOG antibodies detected (2%), with only borderline positivity. Only 1 out of the 29 adult ADEM patients tested anti-MOG seropositive. CONCLUSIONS: MOG antibodies are strongly skewed towards ADS children that present with an ADEM-like disease onset. The presence of such antibodies pleads against a future diagnosis of MS.

Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders.

BACKGROUND: Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. OBJECTIVE: To evaluate the 2012 revised IPMSSG consensus definitions in a cohort of children with ADS prospectively followed from January 2007. METHODS: Children with ADS who had an MRI scan obtained within 90 days after first disease onset were included. The sensitivity and specificity of the 2007 and 2012 IPMSSG consensus definitions were assessed. The time to MS diagnosis applying the 2007 and 2012 definitions was compared using survival analysis and log-rank test. RESULTS: 82 children with ADS were included. 35 children were diagnosed with paediatric MS, of whom 30 experienced a second clinical event. The final diagnosis corresponded applying either the 2007 or 2012 IPMSSG definitions. The revised 2012 definitions had sufficient sensitivity (80%) and high specificity (100%). MS diagnosis was made 3.4 months earlier (χ(2)=8.24, p=0.004) applying the new definitions. In 14 children, MS diagnosis was made at first MRI. CONCLUSIONS: MS diagnosis can be made reliable and early using the 2012 IPMSSG consensus definitions. This is beneficial for adequate counselling of children and their families and for early treatment possibilities.