Maartje Boon

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (13)51.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. To evaluate the 2012 revised IPMSSG consensus definitions in a cohort of children with ADS prospectively followed from January 2007. 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. 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. 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.
    Journal of neurology, neurosurgery, and psychiatry 12/2013; · 4.87 Impact Factor
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    ABSTRACT: To describe the phenotypes and penetrance of paroxysmal kinesigenic dyskinesia (PKD), a movement disorder characterized by attacks of involuntary movements occurring after sudden movements, infantile convulsion and choreoathetosis (ICCA) syndrome, and benign familial infantile convulsions (BFIC), caused by PRRT2 mutations. We performed clinical and genetic studies in 3 large families with ICCA, 2 smaller families with PKD, and 4 individuals with sporadic PKD. Migraine was also present in several individuals. We detected 3 different PRRT2 heterozygous mutations: the recurrent p.Arg217Profs*8 mutation, previously reported, was identified in 2 families with ICCA, 2 families with PKD, and one individual with sporadic PKD; one novel missense mutation (p.Ser275Phe) was detected in the remaining family with ICCA; and one novel truncating mutation (p.Arg217*) was found in one individual with sporadic PKD. In the 2 remaining individuals with sporadic PKD, PRRT2 mutations were not detected. Importantly, PRRT2 mutations did not cosegregate with febrile convulsions or with migraine. The estimated penetrance of PRRT2 mutations was 61%, if only the PKD phenotype was considered; however, if infantile convulsions were also taken into account, the penetrance was nearly complete. Considering our findings and those reported in literature, 23 PRRT2 mutations explain ∼56% of the families analyzed. PRRT2 mutations are the major cause of PKD or ICCA, but they do not seem to be involved in the etiology of febrile convulsions and migraine. The identification of PRRT2 as a major gene for the PKD-ICCA-BFIC spectrum allows better disease classification, molecular confirmation of the clinical diagnosis, and genetic testing and counseling.
    Neurology 08/2012; 79(8):777-84. · 8.25 Impact Factor
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    ABSTRACT: 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.
    Journal of Neurology 02/2012; 259(9):1929-35. · 3.58 Impact Factor
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    ABSTRACT: Acute disseminated encephalomyelitis (ADEM) affects children more frequently than adults. Current studies investigating ADEM in different age groups are difficult to compare. To investigate whether the clinical presentation, outcome and disease course of ADEM differ between adults and children. Disease characteristics of 25 adults and 92 children suffering from ADEM between 1988 and 2008 were compared. The most common presenting symptoms of ADEM in both groups were pyramidal signs and encephalopathy. Ataxia occurred more frequently in children (p  = 0.002). In general, MRI showed ill-defined and large white matter lesions in both groups, whereas periventricular lesions were more prevalent in adults (p = 0.001). In adults, duration of hospitalization was longer (p = 0.002) and intensive care unit (ICU) admission was more frequently required (p = 0.043). Three adults (12%) and one child (1%) died (p = 0.030). Fewer adults had complete motor recovery after their first clinical event (p < 0.001). In 73 patients follow-up time was ≥ 2 years and most of these patients remained monophasic. Although relapses after ADEM can occur, only one adult (5%) and five children (6%) converted to MS. The clinical presentations in children and adults share similarities, but the disease course and outcome of ADEM is more severe in adults with respect to hospitalization, ICU admission, recovery and mortality.
    Multiple Sclerosis 12/2010; 17(4):441-8. · 4.47 Impact Factor
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    ABSTRACT: About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce in paediatric multiple sclerosis. Nevertheless, expertise in this field has grown thanks to recent open-label trials and experience generated in specialized centres. In spring 2009, a first meeting was held in Rotterdam with clinicians from 11 European countries (one from Canada) that are all active in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.
    Multiple Sclerosis 10/2010; 16(10):1258-67. · 4.47 Impact Factor
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    ABSTRACT: Brain MRI is a useful tool for diagnosing inflammatory demyelinating disorders in children. However, it remains unclear which are the most reliable criteria for distinguishing multiple sclerosis (MS) from monophasic disorders such as acute disseminated encephalomyelitis (ADEM). We therefore compared the 4 current sets of MRI criteria in our Dutch pediatric cohort and determined which are the most useful in clinical practice for distinguishing ADEM from MS. We included 49 children who had had a demyelinating event and an MRI scan within 2 months of their first clinical attack. Twenty-one patients had ADEM and remained relapse-free after at least 2 years of follow-up. Twenty-eight patients had a definitive diagnosis of MS. We assessed the sensitivity and specificity of the following MRI criteria: Barkhof criteria, KIDMUS criteria, Callen MS-ADEM criteria, and Callen diagnostic MS criteria. The Callen MS-ADEM criteria had the best combination of sensitivity (75%) and specificity (95%). The KIDMUS criteria had higher specificity (100%), but much lower sensitivity (11%). The Barkhof criteria had a sensitivity of 61% and a specificity of 91%. The Callen diagnostic MS criteria were the most sensitive (82%), but were only 52% specific for distinguishing a first attack of MS from ADEM. The results in our cohort demonstrate that the new Callen criteria for multiple sclerosis-acute disseminated encephalomyelitis (MS-ADEM) are the most useful for differentiating a first attack of MS from monophasic ADEM. Although the Callen diagnostic MS criteria are more sensitive, they lack the specificity necessary to differentiate MS from ADEM.
    Neurology 03/2010; 74(18):1412-5. · 8.25 Impact Factor
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    ABSTRACT: We sought to identify clinical and radiologic features predicting early relapse after a diagnosis of multiple sclerosis in children. In this nationwide retrospective multicenter study in The Netherlands, we included 28 children with multiple sclerosis with onset before age 16 years. Magnetic resonance images and clinical features at the onset of disease were evaluated. The mean follow-up time was 55 months. Twenty children (71%) had a relapse during follow-up. We found that the presence of at least three of four Barkhof magnetic resonance imaging criteria at the onset of multiple sclerosis signs is predictive of early relapse after a diagnosis of multiple sclerosis in children (P<0.05).
    Pediatric Neurology 01/2010; 42(1):53-5. · 1.42 Impact Factor
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    ABSTRACT: Fatigue is an important symptom in adult multiple sclerosis (MS) and it is likely to occur in children with MS. It is currently unknown whether children who experienced a monophasic inflammatory demyelinating event of the central nervous system in the past also suffer from fatigue. We studied the presence and severity of fatigue in 32 children (18 boys, 14 girls) between 11-17 years old (mean: 14 years, 10 months) with a monophasic inflammatory demyelinating disease (n=22) or definite MS (n=10). This was measured with the Checklist Individual Strength. A score of >or=40 on the severity of fatigue subscale indicated the presence of severe fatigue. We also examined the relation between fatigue and depression (assessed by the Child Depression Inventory). Additionally we measured the health-related quality of life (HRQoL), using the TNO-AZL Child Quality of Life child form. We compared the scores of the MS and monophasic patients with the scores of healthy Dutch children. The highest scores on the fatigue scales subjective fatigue and physical activity were found in the children with MS. Only 1 of the monophasic patients suffered from severe fatigue in contrast to 4 of the MS patients. In the MS group fatigue and depression were correlated. MS patients experienced a lower HRQoL on the scales locomotor functioning, cognitive functioning and interaction with peers. The occurrence of fatigue is very rare after a monophasic inflammatory demyelinating event in the past. As expected, fatigue occurs more frequent in paediatric MS patients.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 10/2009; 14(4):320-5. · 2.01 Impact Factor
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    ABSTRACT: Acute gedissemineerde encefalomyelitis (ADEM) en multiple sclerose (MS) bij kinderen zijn relatief zeldzame aandoeningen, waarvan de exacte incidentie onbekend is. De klinische presentatie van een eerste aanval van demyelinisatie in het kader van ADEM bij kinderen kan zeer variabel zijn, evenals het beloop. Onduidelijk is nog welke klinische en biologische parameters voorspellend zijn voor een meer chronisch beloop en progressie tot multiple sclerose. De diagnostische problemen rondom de diagnosen ADEM, MS en verwante aandoeningen worden besproken. Er wordt ingegaan op de differentiaaldiagnose, het aanvullend onderzoek, de behandeling en de prognose. Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) in children are relatively rare and the exact incidence is still unknown. There is great variability in clinical presentation and disease course. It is yet unclear which clinical and biological parameters can predict a chronic disease course and progression to multiple sclerosis. The diagnostic difficulties in distinguishing ADEM, MS and related disorders will be discussed. A review of the differential diagnosis, diagnostic tests, treatment and prognosis is given.
    Tijdschrift voor kindergeneeskunde 01/2009; 77(2):66-72.
  • European Journal of Paediatric Neurology - EUR J PAEDIATR NEUROL. 01/2009; 13.
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    ABSTRACT: To identify clinical, radiologic, or CSF factors that predict conversion to multiple sclerosis (MS) after a first attack of inflammatory demyelination in children. In this nationwide retrospective multicenter study in the Netherlands, 117 children below age 16 were included. Fifty-four children presented with a monofocal clinically isolated syndrome (CIS) and 63 children with a polyfocal CIS (PCIS). A second MS-defining attack occurred in 43% of the CIS cases, compared to 21% of the patients with PCIS onset (p < 0.006). Basal ganglia and thalamic lesions and lesions larger than 2 cm on MRI (considered typical of ADEM) were observed during PCIS, irrespective of the presence of encephalopathy. No significant difference in developing MS was found in children with PCIS with or without encephalopathy. Elevated IgG index and presence of oligoclonal CSF bands were more often observed in children who developed MS. Both Barkhof and KIDMUS MRI criteria shared a high specificity and had a high positive predictive value for conversion to MS. In children under the age of 10, the Barkhof criteria had a higher sensitivity than the KIDMUS criteria, but still lower than in older children. Barkhof and KIDMUS MRI criteria share a high specificity and positive prognostic value for conversion to multiple sclerosis (MS). Sensitivity of these criteria is poor, especially in children below 10 years of age. Basal ganglia lesions can occur in patients who later develop MS. A substantial number of patients presenting with polyfocal onset and no encephalopathy remained monophasic.
    Neurology 07/2008; 71(13):967-73. · 8.25 Impact Factor
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    ABSTRACT: Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterised by congenital muscular dystrophy, structural brain defects, and eye malformations. Typical brain abnormalities are hydrocephalus, lissencephaly, agenesis of the corpus callosum, fusion of the hemispheres, cerebellar hypoplasia, and neuronal overmigration, which causes a cobblestone cortex. Ocular abnormalities include cataract, microphthalmia, buphthalmos, and Peters anomaly. WWS patients show defective O-glycosylation of alpha-dystroglycan (alpha-DG), which plays a key role in bridging the cytoskeleton of muscle and CNS cells with extracellular matrix proteins, important for muscle integrity and neuronal migration. In 20% of the WWS patients, hypoglycosylation results from mutations in either the protein O-mannosyltransferase 1 (POMT1), fukutin, or fukutin related protein (FKRP) genes. The other genes for this highly heterogeneous disorder remain to be identified. To look for mutations in POMT2 as a cause of WWS, as both POMT1 and POMT2 are required to achieve protein O-mannosyltransferase activity. A candidate gene approach combined with homozygosity mapping. Homozygosity was found for the POMT2 locus at 14q24.3 in four of 11 consanguineous WWS families. Homozygous POMT2 mutations were present in two of these families as well as in one patient from another cohort of six WWS families. Immunohistochemistry in muscle showed severely reduced levels of glycosylated alpha-DG, which is consistent with the postulated role for POMT2 in the O-mannosylation pathway. A fourth causative gene for WWS was uncovered. These genes account for approximately one third of the WWS cases. Several more genes are anticipated, which are likely to play a role in glycosylation of alpha-DG.
    Journal of Medical Genetics 01/2006; 42(12):907-12. · 5.70 Impact Factor
  • European Journal of Paediatric Neurology. 11:24.

Publication Stats

272 Citations
51.26 Total Impact Points

Institutions

  • 2008–2013
    • Erasmus MC
      • Department of Neurology
      Rotterdam, South Holland, Netherlands
  • 2009–2010
    • Universitair Medisch Centrum Groningen
      • Department of Neurology
      Groningen, Groningen, Netherlands