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Background Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established. Aim To assess expert opinion on best care practices for patients with CTX using a modified Delphi method. Methods A multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of ≥ 70% Delphi panellists selecting 1–2 (disagreement) or 5–6 (agreement) for 6-point Likert scale questions, or ≥ 70% Delphi panellists choosing the same option for ranking and proportion questions. Results Of the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients’ care. Conclusions The results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX.

Objective: It may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM.Methods: This prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5-16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) >= 4) were assessed during a median follow-up of 37 months (IQR 18-75).Results: In total, 14 patients (29%) experienced >= 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02).Conclusion: Pediatric ATM patients presenting with clinical, radiological and laboratory features associated with multiple sclerosis (MS) are at risk for relapsing disease. In absence of these known MS risk factors at onset of disease these patients are at low risk for relapses. Only a minority of pediatric ATM patients in this cohort have a poor outcome. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V.

BACKGROUND: X-linked adrenoleukodystrophy (ALD) is the most common genetic peroxisomal disorder with an estimated prevalence of 1:15,000. Approximately two-thirds of males with ALD manifest the inflammatory demyelinating cerebral phenotype (cALD) at some disease stage, in which focal, inflammatory lesions progress over months to years. Hematopoietic stem-cell transplantation can permanently halt cALD progression, but it is only effective if initiated early. Although most cALD lesions progress relentlessly, a subset may spontaneously arrest; subsequent reactivation of these arrested lesions has not been previously detailed.OBJECTIVE: We describe a novel arresting-relapsing variant of cALD.METHODS: Salient clinical and radiographic studies were reviewed and summarized for cALD patients with episodic deteriorations.RESULTS: We report a series of five unrelated men with spontaneously arrested cALD lesions that subsequently manifested signs of clinical and radiologic lesion progression during longitudinal follow-up. In three of five patients, functional status was too poor to attempt transplant by the time the recurrence was identified. One patient experienced reactivation followed by another period of spontaneous arrest.CONCLUSIONS: These cases emphasize the need for continued clinical and radiologic vigilance for adult men with ALD to screen for evidence of new or reactivated cALD lesions to facilitate prompt treatment evaluation.

Young children rely on their parents with respect to oral health routines. However, parental knowledge on this topic is often insufficient. Well-child care may be an excellent route to reach parents because almost all of them attend. To evaluate the effectiveness of an 8.5 min web-based film about oral health, provided by well-child care, a non-blinded quasi-experimental study was performed. Parents attending well-child care clinics in the Netherlands were assigned to an intervention (n = 88) or control group (n = 41). The control group received care as usual. We measured parental knowledge of oral health with a questionnaire (range of scores 1–12) before and directly after the intervention, and 6 months later, and assessed differences between the intervention and the control group. Parental oral health knowledge improved after watching the film: the intervention group’s mean score of 11.1 (SD 1.3) was greater than the mean score of 7.1 (SD 2.0) of the control group (Cohen's d = 2.64). Scores remained higher in the intervention group 6 months after watching the film (mean 9.1, SD 1.3) than before (Cohen's d = 1.25). A web-based educational film delivered in a well-child care setting can be an effective way to address oral health and to improve parental knowledge. © 2020 The Authors. Eur J Oral Sci published by John Wiley & Sons Ltd

Item does not contain fulltext BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism. Neurological symptoms are considered to be a clinical hallmark of untreated adult patients. We describe a 'milder CTX phenotype', without neurological involvement. METHODS: We performed a retrospective patient file study in 79 genetically confirmed Dutch patients with CTX (55 patients aged ≥ 21 years) to study the clinical heterogeneity of CTX. We studied the frequency of adult patients with CTX without neurological involvement at diagnosis, in our Dutch cohort, and included a family from South Africa and patients from Italy, USA, Chile and Asia from the literature. RESULTS: In total, we describe 19 adult patients with CTX from 16 independent families, without neurological symptoms at diagnosis. A relatively small percentage (21%, n = 4) had a history of cataract. The majority, 84% (n = 16), presented with tendon xanthomas as the sole or predominant feature. The majority of patients showed increased plasma cholesterol levels. No correlation was found between this 'milder phenotype', the cholestanol levels and the CYP27A1 genotype. In addition, we describe three novel mutations in the CYP27A1 gene. CONCLUSIONS: This study shows the clinical heterogeneity of CTX, highlighting the existence of a 'milder phenotype', that is without neurological involvement at diagnosis. Adult patients with CTX may present with tendon xanthomas as the sole or predominant feature, mimicking familial hypercholesterolemia. It is important to realize that the absence of neurological symptoms does not rule out the development of future neurological symptoms. As CTX is a treatable disorder, early diagnosis and initiation of treatment when additional clinical signs occur is therefore essential.

This fourth in a series of 5 articles in the context of the 2017 Kies-voor-Tanden study presents the results for 17-year-olds. 34% of the 17-year-olds had flawless permanent teeth. In 2017, there were still differences in oral health among the socio-economic groups, to the advantage of the high socio-economic group. The oral health of 17-year-olds had stagnated during the previous 6 years and even appeared to be deteriorating according to some indicators. In addition, knowledge about the dental insurance system after the 18th birthday was poor. Conclusion: The oral health of 17-year-olds had not improved in the previous years. This trend must be followed by monitoring research. In addition, interventions to improve the oral health, knowledge and behaviour of adolescents should be set up and evaluated.In dit vierde artikel in een reeks van 5 naar aanleiding van het Kies-voor-Tandenonderzoek 2017, worden de resultaten van de 17-jarigen samengevat. Van de 17-jarigen had 34% een gaaf blijvend gebit. Er waren in 2017 nog mondgezondheidsverschillen tussen de sociaal-economische groepen waarbij de hoge sociaal-economische groep in het voordeel was. De mondgezondheid van de 17-jarigen was de afgelopen 6 jaar gestagneerd en lijkt op sommige indicatoren zelfs te verslechteren. Daarnaast is het slecht gesteld met de kennis over het tandheelkundige verzekeringsstelsel na de achttiende verjaardag. De conclusie is dat mondgezondheid van de 17-jarigen de afgelopen jaren niet is verbeterd. Deze trend dient te worden gevolgd door monitoringsonderzoek. Daarnaast dienen interventies ter verbetering van mondgezondheid, kennis en gedrag van adolescenten te worden opgezet en geëvalueerd.

This fifth and final in a series of 5 articles in the context of the 2017 Kies-voor-Tanden study presents the results for 23-year-olds. 21% of the 23-year-olds had flawless permanent teeth. In 2017, there were still differences in oral health among the socio-economic (SES) groups, to the advantage of the high SES group. The oral health of the low SES group had shown some improvement in the previous 6 years, while this was not the case within the high SES group. The preventive dental behaviour of 23-year-olds was not optimal and the knowledge about the dental insurance system was poor. Conclusion: the oral health of 23-year-olds had partly improved, partly stagnated. Since not everyone will be able to access information through oral care professionals, other ways of providing information to them must be considered. In the context of public health, to be able to follow trends in oral health and dental preventive behaviour of (young) adults, research monitoring oral health is of great importance.In dit vijfde en laatste artikel in een reeks naar aanleiding van het Kies-voor-Tandenonderzoek 2017, worden de resultaten van de 23-jarigen gepresenteerd. Van de 23-jarigen had 21% een gaaf blijvend gebit. Er waren in 2017 nog mondgezondheidsverschillen tussen de sociaal-economische (SES) groepen waarbij de hoge SES-groep in het voordeel was. De mondgezondheid van de lage SES-groep laat de afgelopen 6 jaar enige verbetering zien terwijl dit bij de hoge SES-groep niet het geval is. Het preventieve tandheelkundig gedrag van 23-jarigen laat te wensen over en de kennis over het tandheelkundige verzekeringsstelsel is matig. De conclusie is dat de mondgezondheid van 23-jarigen deels is verbeterd, deels gestagneerd. Aangezien niet iedereen via een mondzorgverlener aan informatie over mondgezondheid en adequate mondverzorging zal (kunnen) komen, moet nagedacht worden over andere wegen om deze informatie aan hen te verschaffen. Om in het kader van de volksgezondheid ook trends in mondgezondheid en tandheelkundig preventief gedrag van (jong)volwassenen te kunnen volgen is monitoringsonderzoek van groot belang.

ObjectiveTo evaluate the safety and effectiveness of chenodeoxycholic acid (CDCA) treatment in patients with cerebrotendinous xanthomatosis (CTX).MethodsTwo retrospective cohort studies were conducted in CTX patients who underwent CDCA treatment: one in the Netherlands (NL; CDCA-STUK-15-001) and one in Italy (IT; CDCA-STRCH-CR-14-001). Eligible patients were aged 2–75 years, had been diagnosed with CTX, and were treated with CDCA orally for ≥1 year. The impact of CDCA treatment on biochemical markers (including serum cholestanol levels) and disease signs and symptoms were assessed, in addition to the safety and tolerability of CDCA treatment.ResultsA total of 35 patients were screened in the NL study and were diagnosed with CTX at 25.6 (± 13.7 SD) years on average. These patients were treated with CDCA and followed up for a median of 9.00 (range: 0.4–26.3) years. In addition, 28 patients were enrolled in the IT study and were diagnosed at 35.0 (± 11.4 SD) years on average (median duration of CDCA treatment: 5.75 [range: 0.0–25.0] years). Signs and symptoms of disease resolved, improved, or remained stable in many patients, with concomitant improvements in biochemical marker levels (serum cholestanol,p< 0.001; 7α-hydroxy-4-cholesten-3-one,p< 0.001 [IT study]).ConclusionsThe outcomes of these retrospective cohort studies indicate that CDCA is effective in the long-term treatment of CTX, with an acceptable safety profile.

Of all newborns, 1%-2% are born very preterm (VP

Evidence suggests that increased survival over the last decades of very preterm (VPT; gestational age < 32 weeks)– and very low birth weight (VLBW; birth weight < 1500 g)–born infants is not matched by improved outcomes. The objective of our study was to evaluate the reproductive rate, fertility, and pregnancy complications in 35-year-old VPT/VLBW subjects. All Dutch VPT/VLBW infants born alive in 1983 and surviving until age 35 (n = 955) were eligible for a POPS-35 study. A total of 370 (39%) subjects completed a survey on reproductive rate, fertility problems, pregnancy complications, and perinatal outcomes of their offspring. We tested differences in these parameters between the VPT/VLBW subjects and their peers from Dutch national registries. POPS-35 participants had less children than their peers in the CBS registry. They reported more problems in conception and pregnancy complications, including a three times increased risk of hypertension during pregnancy.Conclusion: Reproduction is more problematic in 35-year olds born VPT/VLBW than in the general population, possibly mediated by an increased risk for hypertension, but their offspring have no elevated risk for preterm birth. What is known:At age 28, the Dutch national POPS cohort, born very preterm or with a very low birth in 1983, had lower reproductive rates than the general Dutch population (female 23% versus 32% and male 7% versus 22%).What is new:At age 35, the Dutch POPS cohort still had fewer children than the general Dutch population (female 56% versus 74% and male 40% versus 56%). Females in the POPS cohort had a higher risk of fertility problems and pregnancy complications than their peers in the Dutch national registries, but their offspring had no elevated risk for preterm birth.

HPB : official journal of The International Hepato-Pancreato-Biliary Association 23(9), 1299-1310 (2021). doi:10.1016/j.hpb.2021.04.021, Published by Elsevier, [London]

Background In patients with cerebrotendinous xanthomatosis (CTX), chronic diarrhea is one of the earliest and main symptoms of the disease. In the current study, we evaluated the characteristics of the diarrhea and its response to chenodeoxycholic acid (CDCA) therapy in a cohort of Dutch CTX patients. Methods We performed a retrospective review of medical records for 33 genetically confirmed CTX patients, and abstracted the characteristics of the diarrhea and the response to CDCA therapy (15 mg/kg/day up to 750 mg/day). The Bristol Stool Scale (BSS) was used for qualitative characterization of the stool. Results Twenty‐five patients had diarrhea documented at baseline (76%). Of these patients, 10 had diarrhea rated as 6 (fluffy pieces with ragged edges, a mushy stool), and 6 had diarrhea rated as 7 (watery, no solid pieces, entirely liquid) using the BSS. In 10 patients for whom data were recorded, the median stool frequency at baseline was 3 per day (range 2‐6 per day). The response rate with CDCA for diarrhea resolution was 100% based on at least one post‐baseline visit without diarrhea and 95% as assessed at the first post‐baseline visit. In 68% of cases resolution was complete and sustained as no episodes of diarrhea were documented for follow‐up periods as long as 25 years. Conclusions Chronic diarrhea persisting for years without spontaneous remission is a common feature of CTX at diagnosis. Chenodeoxycholic acid is an effective treatment for symptomatic relief of diarrhea in patients with CTX.

In this retrospective study, we conducted a clinico-genetic analysis of patients with autosomal recessive limb-girdle muscular dystrophy (LGMD) and Miyoshi muscular dystrophy (MMD). Patients were identified at the tertiary referral centre for DNA diagnosis in the Netherlands and included if they carried two mutations in CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TRIM32, FKRP or ANO5 gene. DNA was screened by direct sequencing and multiplex ligand-dependent probe amplification (MLPA) analysis. A total of 244 patients was identified; 68 LGMDR1/LGMD2A patients with CAPN3 mutations (28%), 67 sarcoglycanopathy patients (LGMDR3-5/LGMD2C-E) (27%), 64 LGMDR12/LGMD2L and MMD3 patients with ANO5 mutations (26%), 25 LGMDR2/LGMD2B and MMD1 with DYSF mutations (10%), 21 LGMDR9/LGMD2I with FKRP mutations (9%) and one LGMDR8/LGMD2H patient with TRIM32 mutations (

Item does not contain fulltext Cerebrotendinous xanthomatosis (CTX) is an inborn error of cholesterol and bile acid metabolism, leading to neuropsychiatric and systemic manifestations. Movement disorders have rarely been reported in CTX, while a detailed appreciation of the full phenotypic spectrum is required in order to prevent underdiagnosis of this disease. This review focuses on the frequency of more unusual, non-ataxia and non-spasticity movement disorders reported in CTX. In total, 39 articles were reviewed, describing 55 CTX patients with a movement disorder. Additionally, we report on seven patients with parkinsonism out of our Dutch cohort of 79 (77 genetically proven) CTX patients. Mean age at onset of the movement disorder was 40+/-12 years (median 40, range 13-62 years). Movement disorders can be considered a late disease manifestation. Parkinsonism was the most frequently reported movement disorder, followed by dystonia, myoclonus and postural tremor. Movement disorders were found to be mixed in 23% of patients and were usually part of a complex clinical picture, rather than a prominent symptom. Still, in 18% of the cases, a movement disorder was the presenting symptom. Unusual movement disorders represent a rare clinical feature in CTX, but CTX should be considered in the differential diagnosis of these movement disorders, particularly in case of early onset, and when associated with other neurological features (especially cognitive impairment, pyramidal and cerebellar signs) and/or with systemic features (such as diarrhoea, cataract and tendon xanthomas). CTX is a treatable disorder, stressing the importance of considering CTX as a potential cause of movement disorders.

Pain is a common but often ignored symptom in patients with myotonic dystrophy type 2 (DM2). In this explorative study, we assessed qualitative and quantitative aspects of pain in DM2 using 4 questionnaires and quantitative sensory testing. A disease control group (fibromyalgia [FMS]) as well as healthy controls were used to compare the results, because pain in DM2 shows many clinical similarities to pain in FMS. Thirty-four patients with genetically confirmed DM2 (71% female, mean age 54 years), 28 patients with FMS, and 33 healthy controls were included, age- as well as sex-matched. Pain prevalence was 65% in DM2, 100% in FMS (P

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism (IEM) due to mutations in the CYP27A1 gene. The clinical picture ranges from being nearly asymptomatic in early childhood, up to severe disability at adult age. Infantile-onset diarrhea and juvenile-onset cataract are the earliest symptoms in childhood. In the current study, we evaluated the presence of autism spectrum disorder (ASD) in a large cohort of CTX patients. METHODS: We performed a retrospective patient file study in 77 genetically confirmed Dutch CTX patients to determine the frequency of ASD. In addition, we compared plasma cholestanol levels in CTX patients with and without a diagnosis of ASD and tried to establish a relation between CYP27A1 genotype and ASD. RESULTS: In our CTX cohort, 10 patients (13%; nine pediatric and one adult) with ASD were identified. At the time of diagnosis of ASD, most patients only exhibited symptoms of diarrhea and/or intellectual disability without signs of cataract or neurological symptoms. No correlation was found between the presence of ASD and the level of cholestanol or CYP27A1 genotype. The behavioral problems stabilized or improved after treatment initiation with chenodeoxycholic acid (CDCA) in all pediatric patients. CONCLUSIONS: We conclude that ASD is an early and probably underestimated frequent feature in CTX. Metabolic screening for CTX should be performed in patients with ASD when accompanied by diarrhea, intellectual disability, juvenile cataract, and/or neurological involvement. Early recognition allows for earlier initiation of specific treatment and will improve clinical outcome. Our results add CTX to the list of treatable IEMs associated with ASD.

Our reaction on the letter of Yosiko Myoken et al.(2020): Yosiko Myoken et al. commented on our article about the effect of using a mobile application ("WhiteTeeth") on improving oral hygiene 2 . Although they commended our article, they raised some questions that we would like to respond to. First, Myoken et al. believed that we should have evaluated the effectiveness of our intervention over a longer study period of at least six months to obtain accurate results.

The differential diagnosis of upper extremity mononeuritis multiplex includes neuralgic amyotrophy, vasculitic neuropathy, and Lewis-Sumner syndrome. We describe 3 patients initially suspected of neuralgic amyotrophy, who had an extremely painful, protracted, progressive disease course, not fitting one of these established diagnoses. Nerve ultrasonography showed focal caliber changes of the roots, plexus, and limb nerves. Electromyography showed predominant multifocal axonopathy. Ongoing autoimmune neuropathy was suspected. Steroid treatment provided temporary relief, and intravenous immunoglobulin A sustained pain decrease and functional improvement. These patients appear to have extremely painful axonal inflammatory neuropathy, with a good response to immune-modulating treatment.

Objectives This study aimed to evaluate parents’ Willingness to Invest (WTI) in their children's oral health in terms of money, visits to a dental practice, and brushing minutes. Objectives were to assess the association between parents’ WTI and a) children's dental caries experience, b) children's oral hygiene behavior (OHB), and c) maternal education level and ethnic background. Methods A sample of 630 five to six-year-old-children was recruited from pediatric dental centers in the Netherlands. Children's dmft scores were extracted from personal dental records. Parental questionnaires were used to collect data on parents’ WTI, children's OHB, maternal education level and ethnicity. Results On average, parents were willing to spend a maximum of €37 per month, 3.0 dental visits per year, and 4.5 brushing minutes per day to maintain good oral health for their child. The mean dmft was significantly higher in children whose parents were willing to pay more money and visit the dentist more often (P = 0.028 and P = 0.002, respectively), while the mean dmft was significantly lower in children of parents who were willing to invest more brushing minutes (P

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We report 3 patients with (sub)acute onset of dyspnea and orthopnea caused by bilateral phrenic neuropathy as a neuralgic amyotrophy (NA) subtype. Excruciating pain, weakness, and atrophy were absent at presentation. All 3 patients were middle-aged men and had serologic evidence of acute hepatitis E virus (HEV) infection (IgM and PCR positive). These patients had no history of liver disease or alcohol abuse. Please see table for patient details.

Contains fulltext : 218874.pdf (Publisher’s version ) (Closed access) 01 januari 2020

ObjectiveTo evaluate the effect of chenodeoxycholic acid treatment on disease progression in cerebrotendinous xanthomatosis (CTX).MethodsIn this retrospective cohort study, we report the clinical long-term follow-up characteristics of 56 Dutch patients with CTX. Age at diagnosis was correlated with clinical characteristics and with the course of modified Rankin Scale (mRS) and Expanded Disability Status Scale (EDSS) scores at follow-up.ResultsMedian follow-up time was 8 years (6 months–31.5 years). Patients diagnosed and treated before the age of 24 years had a significantly better outcome at follow-up. When considering only patients with a good treatment adherence (n = 43), neurologic symptoms, if present, disappeared in all patients who were diagnosed before the age of 24 and treated since. Furthermore, treatment prevented the development of new neurologic symptoms during follow-up. In contrast, 61% of the patients diagnosed and treated after the age of 24 showed deterioration of the neurologic symptoms, with parkinsonism as a treatment-resistant feature. There was an improvement or stabilization in favor of patients diagnosed and treated before the age of 24 compared to those treated after the age of 24: 100% vs 58% for mRS scores and 100% vs 50% for EDSS scores, respectively.ConclusionsTreatment start at an early age can reverse and even prevent the development of neurologic symptoms in CTX. This study emphasizes the importance of early diagnosis in CTX and provides a rationale to include CTX in newborn screening programs.

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.

Background Quantitative muscle ultrasound (QMUS) imaging has proven to be a useful, non-invasive technique to visualise normal and pathological skeletal muscle tissue.1 Electromyography (EMG) findings are not always disease specific in patients suspected of idopathic inflammatory myopathies (IIM). Objectives To assess diagnostic value of QMUS in patients suspected for an IIM and to compare results with EMG. Methods In 57 patients, suspected for IIM, panel diagnosis blinded for QMUS was used as reference standard. QMUS results were used to classify patients according an ultrasound neuromuscular disorder (NMD) algorithm (normal/borderline/abnormal). The predictive value of QMUS and EMG was assessed in a two by two table and a multivariate logistic regression model. Results Twenty-two patients (39%) were diagnosed with IIM; 8 polymyositis, 4 dermatomyositis, 4 necrotizing myopathy, 3 inclusion body myositis and 3 non-specific myositis. Sixteen patients were classified with other NMD. We found an increased echointensity of the sternocleidomastoid, biceps, forearm flexor and tibialis anterior in the IIM group. Sensitivity, specificity, positive and negative predictive values (PPV/NPV) were 82%, 51%, 51%, 82% for ultrasound NMD algorithm and 63%, 64%, 50%, 75% for EMG. Multivariate analyses showed area under the curve (AUC) (0.81) (0.69–0.92) for ultrasound NMD algorithm, EMG (0.79) (0.67–0.92) and ultrasound NMD algorithm plus EMG (0.82) (0.70–0.93). Conclusions QMUS with NMD algorithm provides a fair diagnostic value for patients suspected for an IIM and is similar to EMG results. A sizeable NPV indicates a low rate of false negative QMUS results. In addition to the relevant PPV for the presence for NMD, QMUS could serve as a potential screening tool for clinicians to detect possible myopathies and to rule out the presence of IIM. References [1] Zaidman CM, van Alfen N. Ultrasound in the Assessment of Myopathic Disorders. J Clin Neurophysiol. 2016;33(2):103–1 Disclosure of Interest None declared

Item does not contain fulltext OBJECTIVE: The aim was to examine the prevalence of abnormal creatine kinase (CK) and thyroid stimulating hormone (TSH) values and previously unknown myopathy or thyroid disease in patients with suspected FM syndrome (FMS). METHODS: All adult patients with suspected FMS referred to the study hospital between November 2011 and April 2014 could participate. Patients with a history of myopathy or a previous diagnosis of thyroid disorder were excluded. Outcome measures were the percentages of abnormal CK and TSH values and the final diagnosis in those patients. RESULTS: Three hundred and seventy-three patients were included in this study (94% female, mean age 42 years). Of these patients, 7.5% (95% CI: 5.2, 10.6%) had an abnormal CK according to the local reference values. Applying the European Federation of the Neurological Societies guideline, this changed to 0.5% (95% CI: 0.2, 1.9%). In none of these patients was hyperCKaemia-related myopathy diagnosed, and the final diagnosis was FMS in 89% of the patients. Of the total number of patients, 3.5% (95% CI: 2.1, 5.9%) had an elevated TSH and 1.4% (95 CI: 0.6, 3.1%) a lowered TSH, with one patient having a somewhat lowered free thyroid hormone level. The final diagnosis was FMS in all these patients. CONCLUSION: Abnormal CK and TSH values are rare in patients with suspected FMS and do not result in an alternative diagnosis. Therefore, it seems that routine testing of CK and TSH levels in patients with suspected FMS referred to secondary care does not contribute to the diagnostic process.

We present a two-week old girl who was diagnosed with cerebrotendinous xanthomatosis (CTX), an inborn error of bile acid synthesis, after a diagnostic workup for convulsions which were shown to be caused by a parechovirus encephalitis. The diagnosis of CTX was confirmed with CYP27A1 mutation analysis. She was started on chenodeoxycholic acid (CDCA) supplementation, which inhibits cholestanol production through a feedback mechanism, at the advised dosage of 15 mg/kg/day. Within 6 weeks, she developed jaundice with hepatomegaly. CDCA supplementation was stopped after which liver size and function rapidly normalised. CDCA supplementation was then restarted and maintained at 5 mg/kg/day. Cholestanol, liver enzymes and total bilirubin were frequently monitored in the patient, who is now 2.8 years of age, and have remained within normal range. Her psychomotor development has been normal. Conclusion: adequate metabolic control was achieved in an infant with CTX with CDCA supplementation at a dosage of 5 mg/kg/day and was well tolerated. CDCA supplementation at 15 mg/kg/day seems hepatotoxic in infants and should not be used. This is relevant in view of the possible inclusion of CTX in newborn screening programs in the near future. What is Known: • Cerebrotendinous xanthomatosis (CTX), an inborn error of bile acid synthesis, is a progressive neurological disorder. • Symptoms of CTX can be halted, and likely prevented, with chenodeoxycholic acid (CDCA) supplementation, making CTX a good candidate for newborn screening. What is New: • CDCA supplementation at the advised dosage of 15 mg/kg/day in children seems hepatoxic in infants with CTX.• Adequate metabolic control in an infant with CTX was achieved with CDCA supplementation at 5 mg/kg/day and well tolerated.

Peripheral neuropathy in patients with merosin-negative congenital muscular dystrophy (MN-CMD) has been sporadically investigated and has been considered to be motor and demyelinating in nature on the basis of nerve conduction studies. We performed neurophysiologic studies in 12 children with MN-CMD to establish the spectrum and evolution of peripheral nervous system involvement. In our patients, nerve conduction studies for both motor and sensory nerves were near normal in the children younger than six months and abnormal in the older children. The older children had the relatively slowest nerve conduction velocities suggesting a progressive, age-related dysmyelinating neuropathy. We hypothesize that the findings are due to a myelination arrest as a result of insufficient synthesis and maintenance of the peripheral myelin sheath. (J Pediatr Neurol 2004; 2(4): 213–218).

Item does not contain fulltext BACKGROUND: This report highlights the differential diagnosis of predominant cerebellar white matter abnormalities with dentate nuclei involvement. PATIENT DESCRIPTION: We describe two individuals with Langerhans cell histiocytosis in whom the diagnosis of cerebrotendinous xanthomatosis was initially considered. The clinical picture consisted of a progressive cerebellar syndrome with typical magnetic resonance imaging abnormalities. In both individuals, the cerebellar syndrome preceded the diagnosis of Langerhans cell histiocytosis. CONCLUSIONS: The magnetic resonance imaging abnormalities and neurological features in patients with Langerhans cell histiocytosis can be strikingly similar to those with cerebrotendinous xanthomatosis. In cerebrotendinous xanthomatosis, the cerebellar symptoms and cerebellar white matter abnormalities are usually seen in adult patients. In a pediatric patient with a cerebellar syndrome, showing these cerebellar white matter abnormalities a diagnosis of Langerhans cell histiocytosis is more likely.

Background Adolescents with fixed orthodontic appliances are at high risk of developing dental caries. To date, new smartphone technologies have seldom been used to support them in the preventive behavior that can help prevent dental caries. After an intervention-mapping process, we developed a smartphone application (the WhiteTeeth app) for preventing dental caries through improved oral-health behavior and oral hygiene. The app, which is intended to be used at home, will help adolescents with fixed orthodontic appliances perform their oral self-care behavior. The app is based on the Health Action Process Approach (HAPA) theory, and incorporates several behavior-change techniques that target the psychosocial factors of oral-health behavior. This article describes the protocol of a randomized controlled trial (RCT) to evaluate the effects of the WhiteTeeth app on oral-health behavior and oral-hygiene outcomes (presence of dental plaque and gingival bleeding) compared with those of care as usual, in patients aged 12–16 with fixed orthodontic appliances. Methods/design The RCT has two conditions: an experimental group that will receive the WhiteTeeth app in addition to care as usual, and a control group that will only receive care as usual. Care as usual will include routine oral-health education and instruction at orthodontic check-ups. In the western part of the Netherlands 146 participants will be recruited from four orthodontic clinics. Data will be collected during three orthodontic check-ups: baseline (T0), 6 weeks of follow-up (T1) and 12 weeks of follow-up (T2). The primary study outcomes are the presence of dental plaque (measured with a modified Silness and Loë Plaque Index); and gingival bleeding (measured with the Bleeding on Marginal Probing Index). Secondary outcomes include changes in self-reported oral-health behaviors and its psychosocial factors identified by the HAPA theory, such as outcome expectancies, intention, action self-efficacy, coping planning and action control. Discussion Since the intervention was designed to target psychosocial factors in the motivational and volitional components of the behavior-change process, we hypothesize that the app will cause greater improvements in oral-health behavior and oral hygiene more than traditional oral-health-promotion programs (i.e., care as usual). Trial registration. The trial has been registered with the Dutch Trial Register (NTR6206: 20 February 2017). Electronic supplementary material The online version of this article (10.1186/s12903-018-0475-9) contains supplementary material, which is available to authorized users.

Item does not contain fulltext We describe four unrelated patients with the same de novo heterozygous missense mutation c.751C>T in the DYNC1H1 gene. We found a high phenotype-genotype correlation with all four patients having early childhood-onset predominant lower limb muscle weakness and wasting which was slowly progressing and later-onset mild upper extremities proximal weakness. All four patients presented minor cognitive dysfunction with learning difficulty and developmental behavioural comorbidities with mild abnormalities in the brain MRI. The leg muscle MRI findings are highly consistent in DYN1CH1-related spinal muscular atrophy with lower limb predominance (SMALED) with relative sparing of biceps femoris and semitendinosus, and hypertrophy of adductor longus in the thighs; and sparing the anterior and medial muscles in the calves. This report provides important clinical evidence indicating the de novo heterozygous missense mutation c.751C>T in the DYNC1H1 gene is pathogenic causing SMALED. Muscle MRI is more specific than muscle biopsy in the diagnosis of SMALED.

A boy presented at the age of 3.5 months with a developmental delay. He developed infantile spasms with hypsarrhytmia on EEG 1 month later. Additional symptoms were delayed visual development, asymmetrical hearing loss, hypotonia, and choreoathetoid movements. He also had some dysmorphic features and was vulnerable for infections. He was treated successively with vigabatrin, prednisolone, valproic acid, nitrazepam, and lamotrigine without a lasting clinical effect, but showed a treatment response to levetiracetam. Cerebral MRI showed hypoplasia of the corpus callosum and a mild delay in myelination. Further investigations including metabolic screening and glycosylation studies by transferrin isoelectric focusing were all considered to be normal. Whole-exome sequencing identified a de novo mutation in the ALG13 gene (c.320A>G, p.(Asn107Ser)). Mutations in this gene, which is located on the X-chromosome, are associated with congenital disorders of glycosylation type I (CDG-I). Mass spectrometric analysis of transferrin showed minor glycosylation abnormalities. The c.320A>G mutation in ALG13 has until now only been described in girls and was thought to be lethal for boys. All girls with this specific mutation presented with a similar phenotype of developmental delay and severe early onset epilepsy. In two girls glycosylation studies were performed which showed a normal glycosylation pattern. This is the first boy presenting with an epileptic encephalopathy caused by the c.320A>G mutation in the ALG13 gene. Since glycosylation studies are near-normal in patients with this mutation, the diagnosis of ALG13-CDG can be missed if genetic studies are not performed.

[This corrects the article DOI: 10.1002/acn3.725.].

This cross-sectional study empirically tested a theoretical model of pathways and inter-relationships among community, family, and individual determinants of childhood dental caries in a sample of 630, 6-year-old children from the Netherlands. Children's decayed, missing, and filled teeth (dmft) scores were extracted from dental records. A validated parental questionnaire was used to collect data on sociodemographic characteristics, psychosocial factors, and oral hygiene behaviours. Data on neighbourhood quality were obtained from the Dutch Central Bureau of Statistics. Structural equation modelling indicated that the model was valid after applying a few modifications. In the revised model, lower maternal education level was related to poorer family organization, lower levels of social support, lower dental self-efficacy, and an external dental health locus of control. These, in turn, were associated with poorer oral hygiene behaviours, which were linked to higher levels of childhood dental caries. In addition, lower maternal education level and poorer neighbourhood quality were directly associated with higher caries levels in children. This model advances our understanding of determinants of childhood dental caries and the pathways in which they operate. Conception of these pathways is essential for guiding the development of caries-preventive programmes for children. Clues for further development of the model are suggested. © 2014 Eur J Oral Sci.

The Dutch National Health Care Institute, formerly CVZ/Ziekenfondsraad, asked TNO to investigate oral health in adults in the Netherlands 4 times in the period from 1995 to 2013 in order to monitor trends in oral health and, if necessary, to be able to adjust their policies accordingly. With the results of these 4 studies, the trends in caries experience of 25- up to and including 54-year-olds during the period 1995 to 2013 were established. In 1995, 2002, 2007 and 2013, the oral health of 25- up to and including 54-year-olds living in 's-Hertogenbosch was determined by means of a questionnaire and a clinical oral examination. In the period 1995-2013 a reduction in caries experience was found in both well- and less well-educated individuals. The outcomes for well-educated individuals were more favourable than those of their less well-educated peers. In 2012, then, oral health still has a socio-economic gradient. The debate on how to reach the high-risk group remains a matter of concern both for the dental profession and for politicians. In order to be able to keep a finger on the pulse monitoring of caries experience is of great importance.Zorginstituut Nederland, voorheen CVZ/ Ziekenfondsraad, heeft de mondgezondheid van volwassenen in Nederland in de periode 1995-2013 viermaal door TNO laten onderzoeken om trends in de mondgezondheid te monitoren en, indien nodig, beleidsmatige aanpassingen te kunnen doen. Met de gegevens uit deze 4 onderzoeken zijn de trends in cariëservaring bij 25- tot en met 54-jarigen gedurende 1995-2013 vastgesteld. In 1995, 2002, 2007 en 2013 werd de mondgezondheid van 25- tot en met 54-jarigen in ‘s Hertogenbosch in kaart gebracht door middel van een vragenlijst en een klinisch mondonderzoek. Over de periode 1995-2013 werd een afname in cariëservaring gevonden bij zowel hoog- als laagopgeleiden, waarbij hoogopgeleiden gunstiger uitkomsten hadden dan hun laagopgeleide leeftijdsgenoten. Anno 2012 kent mondgezondheid derhalve nog steeds een sociaaleconomische gradiënt. Het debat over hoe de groep met een hoog cariësrisico te bereiken blijft een punt van aandacht voor zowel de mondzorgprofessie als voor de politiek. Monitoring van de cariëservaring is van groot belang om een vinger aan de pols te kunnen houden.

A 54-year-old man with a medical history notable for diabetes mellitus and coronary artery bypass surgery presented to the emergency department with acute-onset vertigo, diplopia, hemiparesis, and hemihypesthesia of his left arm and leg. On cranial nerve examination, he displayed a conjugate right horizontal gaze palsy, diminished right eye adduction, horizontal left-beating nystagmus on leftward gaze, paralytic pontine exotropia of the left eye, gaze-evoked vertical nystagmus, and peripheral right facial palsy (figure 1; video at [Neurology.org][1]). These features were consistent with an ischemic pontine lesion affecting the right (1) paramedian pontine reticular formation and medial longitudinal fasciculus (one-and-a-half syndrome), (2) facial nerve fascicle (seventh cranial nerve palsy), (3) corticospinal tract, and (4) medial lemniscus pathway (the latter 2 comprising the final “half syndrome”) (figure 2), thereby constituting the so-called nine syndrome.1 [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000004271

Purpose: Although survival after very preterm birth (VP)/very low birth weight (VLBW) has improved, a significant number of VP/VLBW individuals develop physical and cognitive problems during their life course that may affect their health-related quality of life (HRQoL). We compared HRQoL in VP/VLBW cohorts from two countries: The Netherlands (n = 314) versus Germany (n = 260) and examined whether different neonatal treatment and rates of disability affect HRQoL in adulthood.\ud \ud Method: To analyse whether cohorts differed in adult HRQoL, linear regression analyses were performed for three HRQoL outcomes assessed with the Health Utilities Index 3 (HUI3), the London Handicap Scale (LHS), and the WHO Quality of Life instrument (WHOQOL-BREF). Stepwise hierarchical linear regression was used to test whether neonatal physical health and treatment, social environment, and intelligence (IQ) were related to VP/VLBW adults’ HRQoL and cohort differences.\ud \ud Results: Dutch VP/VLBW adults reported a significantly higher HRQoL on all three general HRQoL measures than German VP/VLBW adults (HUI3: .86 vs .83, p = .036; LHS: .93 vs. .90, p = .018; WHOQOL-BREF: 82.8 vs. 78.3, p < .001). Main predictor of cohort differences in all three HRQoL measures was adult IQ (p < .001).\ud \ud Conclusions: Lower HRQoL in German versus Dutch adults was related to more cognitive impairment in German adults. Due to different policies, German VP/VLBW infants received more intensive treatment that may have affected their cognitive development. Our findings stress the importance of examining effects of different neonatal treatment policies for VP/VLBW adults’ life.

Hypertrophic differentiation occurs during in vitro chondrogenesis of mesenchymal stem cells (MSCs), decreasing the quality of the cartilage construct. Previously we identified WNT pathway antagonists Dickkopf 1 homolog (DKK1) and frizzled-related protein (FRZB) as key factors in blocking hypertrophic differentiation of human MSCs (hMSCs). In this study, we investigated the role of endogenously expressed DKK1 and FRZB in chondrogenesis of hMSC and chondrocyte redifferentiation and in preventing cell hypertrophy using three relevant human cell based systems, isolated hMSCs, isolated primary human chondrocytes (hChs), and cocultures of hMSCs with hChs for which we specifically designed neutralizing nano-antibodies. We selected and tested variable domain of single chain heavy chain only antibodies (VHH) for their ability to neutralize the function of DKK1 or FRZB. In the presence of DKK1 and FRZB neutralizing VHH, glycosaminoglycan and collagen type II staining were significantly reduced in monocultured hMSCs and monocultured chondrocytes. Furthermore, in cocultures, cells in pellets showed hypertrophic differentiation. In conclusion, endogenous expression of the WNT antagonists DKK1 and FRZB is necessary for multiple steps during chondrogenesis: first DKK1 and FRZB are indispensable for the initial steps of chondrogenic differentiation of hMSCs, second they are necessary for chondrocyte redifferentiation, and finally in preventing hypertrophic differentiation of articular chondrocytes.

Some patients with myasthenia gravis (MG) have autoantibodies to muscle specific kinase (MuSK) instead of the acetylcholine receptor (AChR). Anti-AChR antibodies may be transferred across the placenta causing a self-limiting neonatal myasthenic syndrome. We describe an infant with a similar disorder whose mother had MuSK MG. ### Case report. In September 1994, the mother noticed unilateral ptosis and a feeling of generalized fatigue at age 13. Over the next months, she developed severe oculobulbar weakness, dyspnea, and weakness of the neck. Symptoms were fluctuating and unresponsive to acetylcholinesterase inhibitors. No antibodies to the AChR were found. In 1995, a normal thymus was removed. High doses of prednisone had little effect. In 1997, plasmapheresis induced a partial remission and this became her regular therapy for several years. In 2004 anti-MuSK antibodies were found. She had two first trimester miscarriages while using pyridostigmine and prednisone in September and December 2004. In May 2005, she became pregnant using only prednisone 20 mg on alternating days. This pregnancy was uneventful without large fluctuations of her myasthenic symptoms. In February 2006, at 38 + 1 week of gestation, she unaidedly delivered a boy in head position. Apgar score was 10 after 1 and 5 minutes. Birthweight was 3,190 g (P25). Physical examination was unremarkable. After 8 hours, however, drinking became difficult. After 16 hours, he showed mild generalized hypotonia with diminished facial expression …

Item does not contain fulltext Myasthenia gravis is a paralytic disorder with autoantibodies against acetylcholine receptors at the neuromuscular junction. A proportion of patients instead has antibodies against muscle-specific kinase, a protein essential for acetylcholine receptor clustering. These are generally of the immunoglobulin-G4 subclass and correlate with disease severity, suggesting specific myasthenogenic activity. However, immunoglobulin-G4 subclass antibodies are generally considered to be 'benign' and direct proof for their pathogenicity in muscle-specific kinase myasthenia gravis (or other immunoglobulin-G4-associated disorders) is lacking. Furthermore, the exact electrophysiological synaptic defects caused at neuromuscular junctions by human anti-muscle-specific kinase autoantibodies are hitherto unknown. We show that purified immunoglobulin-G4, but not immunoglobulin-G1-3, from patients with muscle-specific kinase myasthenia gravis binds to mouse neuromuscular junctions in vitro, and that injection into immunodeficient mice causes paralysis. Injected immunoglobulin-G4 caused reduced density and fragmented area of neuromuscular junction acetylcholine receptors. Detailed electrophysiological synaptic analyses revealed severe reduction of postsynaptic acetylcholine sensitivity, and exaggerated depression of presynaptic acetylcholine release during high-rate activity, together causing the (fatigable) muscle weakness. Intriguingly, compensatory transmitter release upregulation, which is the normal homeostatic response in acetylcholine receptor myasthenia gravis, was absent. This conveys extra vulnerability to neurotransmission at muscle-specific kinase myasthenia gravis neuromuscular junctions. Thus, we demonstrate that patient anti-muscle-specific kinase immunoglobulin-G4 is myasthenogenic, independent of additional immune system components, and have elucidated the underlying electrophysiological neuromuscular junction abnormalities. 01 april 2012

Item does not contain fulltext 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 (

We here report a 13-year-old Marfan patient who suffered from severe, medication-resistant, intermittent headache, which was provoked when getting into an upright position and immediately relieved by lying down or after intravenous rehydration. The postural benefit and the sudden relief after intravenous hydration suggested (intermittent) intracranial hypotension, although a normal opening pressure on lumbar punction was observed and no cerebrospinal fluid (CSF) leakage was identified. Imaging studies revealed severe dural ectasia at lumbosacral level, and two intradural cysts and two extradural presacral cysts were detected. Most likely, altered hydrodynamics in intra- and extracranial spinal meningeal cysts caused intermittent CSF hypotension above these cysts, resulting in intermittent intracranial hypotension. Surgical marsupialisation of the intradural cysts proved to be effective. This resulted in a significant reduction of the headache during the clinical follow-up of eight years.

Bij drie kinderen werd de diagnose neuroborreliose gesteld, zij presenteerden zich allen met atypische hoofdpijn en systemische klachten. Na het stellen van de diagnose neuroborreliose op basis van het klinische beeld en serologie werden ze behandeld met ceftriaxon gedurende 14 dagen. Met deze behandeling herstelden de patienten volledig. Neuroborreliose is, na het bekende erythema migrans, de meest voorkomende presentatievorm van lyme-borreliose. Bij kinderen zijn atypische hoofdpijn en perifere facialisparese vaak de eerste en tevens belangrijkste symptomen. Deze kunnen gepaard gaan met aseptische meningitis, koorts en aspecifieke klachten zoals vermoeidheid en stijfheid. Bij verdenking op neuroborreliose dient Borrelia-serologie (IgG en IgM) te worden bepaald. De aanwezigheid van intrathecale antistoffen en de liquor/serumratio kunnen helpen bij het stellen van de diagnose neuroborreliose.

Cerebrotendinous xanthomatosis (CTX) is an inborn error of bile acid synthesis in which hepatic conversion of cholesterol to cholic and chenodeoxycholic acids is impaired. Patients have abnormal bile alcohols in urine, normal to increased plasma cholesterol concentrations and increased concentrations of plasma cholestanol. Little is known about cholesterol precursors in CTX, however. We studied cholesterol and phytosterol profiles in two siblings with CTX during follow-up. While cholesterol concentrations were low in both patients, plasma cholestanol was 6-fold higher compared to control values. In addition, both siblings had a more than 100-fold increase in 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC). Lathosterol, lanosterol and sitosterol were increased in both patients while concentrations of desmosterol and campesterol were normal. In addition, plasma lathosterol/cholesterol ratios were significantly elevated. After treatment with chenodeoxycholate, both patients showed a marked decrease in cholestanol, 7DHC, 8DHC, lathosterol, lanosterol and sitosterol. In addition, the lathosterol/cholesterol ratio normalized, indicating that overall cholesterol synthesis was sufficiently suppressed. This study shows that elevated cholesterol precursors, other than cholestanol, can be a hallmark for CTX.

Item does not contain fulltext OBJECTIVE: To identify clinical, radiologic, or CSF factors that predict conversion to multiple sclerosis (MS) after a first attack of inflammatory demyelination in children. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

OBJECTIVE. The goal was to compare health-related quality of life of 12- to 16-year-old adolescents born at an extremely low birth weight in regional cohorts from Ontario (Canada), Bavaria (Germany), and the Netherlands. METHODS. Patients were extremely low birth weight survivors from Canada, Germany, and the Netherlands. Health-related quality of life was assessed with Health Utilities Index 3. Missing data were substituted by proxy reports. Differences in mean Health Utilities Index 3 scores were tested by using analysis of variance. Differences in the numbers of children with affected attributes were tested by using logistic regression analyses. RESULTS. Survival rates were similar; response rates varied between 71% and 90%. Significant differences in health-related quality of life were found between the cohorts, with Dutch children scoring highest on Health Utilities Index 3 and German children scoring lowest, independent of birth weight, gestational age, and cerebral palsy. Differences in mean utility scores were mainly attributable to differences in the cognition health attribute. Most of the results were corroborated by logistic regression analyses. CONCLUSIONS. There were significant differences between the 3 cohorts in health-related quality of life, not related to differences in birth weight, gestational age, or cerebral palsy. Survival and response rates alone cannot explain these differences.

Item does not contain fulltext Myotonic dystrophy type 2 (DM2) is a rare, autosomal dominant, multisystem disorder with proximal weakness, myotonia, pain and cataract as important symptoms. Given the assumed underreporting of DM2 in the Netherlands combined with the predominant role of pain in DM2 as well as in fibromyalgia syndrome (FMS), we hypothesized there will be an excess prevalence of DM2 in patients with (suspected) FMS. Our objective was to determine the prevalence of DM2 in patients with suspected FMS. A prevalence of 2% was considered a relevant excess frequency. Between November 2011 and April 2014, 398 patients with suspected FMS who had been assessed by a rheumatologist participated in this cross-sectional study. 95% of the study population was female, with a mean age of 42 years. The final ICD-9 diagnoses were collected, in 96% the diagnosis was FMS. 92% met the 2010 American College of Rheumatology (ACR) diagnostic criteria for FMS. A questionnaire including neuromuscular symptoms was completed. Creatine kinase was determined, and genetic testing for DM2 was conducted in all patients. DM2 was established in only one patient (0.25%, 95% CI 0.04-1.4%), thus disapproving our hypothesis of a relevant prevalence of 2%. Our results suggest that patients with suspected FMS should not routinely be tested for DM2.

BackgroundObesity and dental caries are widely-recognised problems that affect general health. The prevention of both dental caries and obesity have proven very difficult: children and their parents may need professional support to achieve behaviour change. To find out whether both dental caries and overweight in childhood can be targeted using a common risk factor approach, it is necessary to establish whether the two diseases are indeed linked. The aim of the present study was therefore to use anthropometric data obtained professionally to investigate the association between Body Mass Index and dental caries experience in children aged 5-8 years receiving treatment in a referral centre for paediatric dental care in the Netherlands.MethodsChildren’s dmft and dmfs scores were calculated using dental records and sociodemographic data were also extracted from these records. Dentists were trained to measure standing height and weight in a standardised way. Body Mass Index was calculated by dividing kilograms by height squared (kg/m2). Extended International (International Obesity Task Force) body mass index cut-offs were used to define ‘no overweight’ and ‘overweight’ (with the latter category including obesity).ResultsNo statistically significant differences were found between the mean dmft or dmfs scores of the two groups (overweight and non-overweight), even after correction for the effect of the potential confounders sex, socio-economic status and ethnicity. The percentage of caries-active children in the non-overweight group was almost the same as in the overweight group. No statistically significant differences were found.ConclusionsWe hypothesised to find a positive association between body mass index and dental caries experience in children aged 5-8 years attending our practice. However, this study did not find a relationship of this kind. A common risk factor approach for the prevention of caries and overweight is therefore not supported by our study.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help in maintaining FSHD muscle function. Our primary objective was to test whether oral administration of vitamin C, vitamin E, zinc gluconate, and selenomethionine could improve the physical performance of patients with FSHD. Adult patients with FSHD (n=53) were enrolled at Montpellier University Hospital (France) in a randomized, double-blind, placebo-controlled pilot clinical trial. Patients were randomly assigned to receive 500 mg vitamin C, 400mg vitamin E, 25mg zinc gluconate and 200 μg selenomethionine (n=26), or matching placebo (n=27) once a day for 17 weeks. Primary outcomes were changes in the two-minute walking test (2-MWT), maximal voluntary contraction, and endurance limit time of the dominant and nondominant quadriceps (MVCQD, MVCQND, TlimQD, and TlimQND, respectively) after 17 weeks of treatment. Secondary outcomes were changes in the antioxidant status and oxidative stress markers. Although 2-MWT, MVCQ, and TlimQ were all significantly improved in the supplemented group at the end of the treatment compared to baseline, only MVCQ and TlimQ variations were significantly different between groups (MVCQD: P=0.011; MVCQND: P=0.004; TlimQD: P=0.028; TlimQND: P=0.011). Similarly, the vitamin C (P