Hendriekje Eggink

Dystonia in children and adolescents: a systematic review and a new diagnostic algorithm

Early aetiological diagnosis is of paramount importance for childhood dystonia because some of the possible underlying conditions are treatable. Numerous genetic and non-genetic causes have been reported, and diagnostic workup is often challenging, time consuming and costly. Recently, a paradigm shift has occurred in molecular genetic diagnostics, with next-generation sequencing techniques now allowing us to analyse hundreds of genes simultaneously. To ensure that patients benefit from these new techniques, adaptation of current diagnostic strategies is needed. On the basis of a systematic literature review of dystonia with onset in childhood or adolescence, we propose a novel diagnostic strategy with the aim of helping clinicians determine which patients may benefit by applying these new genetic techniques and which patients first require other investigations. We also provide an up-to-date list of candidate genes for a dystonia gene panel, based on a detailed literature search up to 20 October 2014. While new genetic techniques are certainly not a panacea, possible advantages of our proposed strategy include earlier diagnosis and avoidance of unnecessary investigations. It will therefore shorten the time of uncertainty for patients and their families awaiting a definite diagnosis.

Large observer variation of clinical assessment of dyspnoeic wheezing children.

Background In children with acute dyspnoea, the assessment of severity of dyspnoea and response to treatment is often performed by different professionals, implying that knowledge of the interobserver variation of this clinical assessment is important. Objective To determine intraobserver and interobserver variation in clinical assessment of children with dyspnoea. Methods From September 2009 to September 2010, we recorded a convenience sample of 27 acutely wheezing children (aged 3 months–7 years) in the emergency department of a general teaching hospital in the Netherlands, on video before and after treatment with inhaled bronchodilators. These video recordings were independently assessed by nine observers scoring wheeze, prolonged expiratory phase, retractions, nasal flaring and a general assessment of dyspnoea on a Likert scale (0–10). Assessment was repeated after 2 weeks to evaluate intraobserver variation. Results We analysed 972 observations. Intraobserver reliability was the highest for supraclavicular retractions (κ 0.84) and moderate-to-substantial for other items (κ 0.49–0.65). Interobserver reliability was considerably worse, with κ<0.46 for all items. The smallest detectable change of the dyspnoea score (>3 points) was larger than the minimal important change (<1 point), meaning that in 69% of observations a clinically important change after treatment cannot be distinguished from measurement error. Conclusions Intraobserver variation is modest, and interobserver variation is large for most clinical findings in children with dyspnoea. The measurement error induced by this variation is too large to distinguish potentially clinically relevant changes in dyspnoea after treatment in two-thirds of observations. The poor interobserver reliability of clinical dyspnoea assessment in children limits its usefulness in clinical practice and research, and highlights the need to use more objective measurements in these patients.

Clinical Scores for Dyspnoea Severity in Children: A Prospective Validation Study.

Background In acute dyspnoeic children, assessment of dyspnoea severity and treatment response is frequently based on clinical dyspnoea scores. Our study aim was to validate five commonly used paediatric dyspnoea scores. Methods Fifty children aged 0–8 years with acute dyspnoea were clinically assessed before and after bronchodilator treatment, a subset of 27 children were videotaped and assessed twice by nine observers. The observers scored clinical signs necessary to calculate the Asthma Score (AS), Asthma Severity Score (ASS), Clinical Asthma Evaluation Score 2 (CAES-2), Pediatric Respiratory Assessment Measure (PRAM) and respiratory rate, accessory muscle use, decreased breath sounds (RAD). Results A total of 1120 observations were used to assess fourteen measurement properties within domains of validity, reliability and utility. All five dyspnoea scores showed overall poor results, scoring insufficiently on more than half of the quality criteria for measurement properties. The AS and PRAM were the most valid with good values on six and moderate values on three properties. Poor results were mainly due to insufficient measurement properties in the validity and reliability domains whereas utility properties were moderate to good in all scores. Conclusion This study shows that commonly used dyspnoea scores show insufficient validity and reliability to allow for clinical use without caution.

Dystonia‐deafness syndrome caused by a β‐actin gene mutation and response to deep brain stimulation

Dystonia‐deafness syndrome is a distinct clinical presentation within the dystonia‐spectrum. Although several genetic and acquired causes have been reported, etiology remains unknown in the majority of patients.

The Burke-Fahn-Marsden Dystonia Rating Scale is Age-Dependent in Healthy Children

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Teaching Video NeuroImages: The “round the houses” sign as a clinical clue for Niemann-Pick disease type C

A 58-year-old man presented with progressive involuntary jerky movements. In addition to a cortical myoclonus, supported by polymyographic evaluation, we saw a “looping” trajectory of the vertical saccades, also referred to as the “round the houses” sign (video on the Neurology® Web site at Neurology.org).

Cognition in Childhood Dystonia : A systematic review

Cognitive impairments have been established as part of the non‐motor phenomenology of adult dystonia. In childhood dystonia, the extent of cognitive impairments is less clear. This systematic review aims to present an overview of the existing literature to elucidate the cognitive profile of primary and secondary childhood dystonia.

Neurometabolic disorders are treatable causes of dystonia

A broad range of rare inherited metabolic disorders can present with dystonia. For clinicians, it is important to recognize dystonic features, but it can be complicated by the mixed and complex clinical picture seen in many neurometabolic patients. Careful phenotyping is the first step towards the diagnosis of the underlying condition and subsequent targeted treatment, further supported by imaging, biochemical diagnostics and the availability of modern diagnostic techniques such as next generation sequencing. As several neurometabolic disorders are treatable causes of dystonia, these should have priority in the diagnostic process. In the symptomatic treatment of dystonia, several therapeutic options are available. Awareness for the occurrence and optimal treatment of dystonia and other movement disorders in neurometabolic conditions is important because these symptoms can have a substantial impact on the quality of life and daily functioning; this effect is not only exerted by the dystonia itself, but also by the frequently associated non-motor features. In this paper, the highlights and key concepts of neurometabolic forms of dystonia are discussed, with a focus on phenomenology, the diagnostic approach, the most important neurometabolic aetiologies, co-occurring non-motor features and therapeutic options.

PP12.3 – 2284: Crossing barriers: The importance of a multidisciplinary approach to young-onset movement disorders

Objective Management of young-onset movement disorders is often challenging. The ideal approach requires a broad spectrum of skills and knowledge of the clinician, including (1) correct classification; (2) differentiation of normal and abnormal development; (3) knowledge of the possible acquired and genetic aetiologies, including metabolic diseases; and (4) knowledge of current genetic diagnostic strategies. Therefore, we initiated a specialised multidisciplinary outpatient clinic for young-onset movement disorders, with a team consisting of an adult neurologist specialised in movement disorders, paediatric neurologist, clinical geneticist and paediatrician specialised in metabolic diseases and genetics. The aim of this observational study was to report our experience. Methods The medical records of the first 100 patients who visited the multidisciplinary outpatient clinic were reviewed. We compared the movement disorder classification, (supposed) etiological diagnosis and treatment strategies before and after the visit. In addition, we evaluated the effects of initiated therapies as reported by the patients or their caregivers. Results Patients (n=100) had an age of 12.5 years ± 6.3 and 56 of them were boys. The mean onset age of the symptoms was 3.4 years ± 5.3. Referring specialists were predominantly (paediatric) neurologists (74%) with as main referring questions classification (50%), etiological diagnosis (38%) and treatment options for the movement disorder (42%). In 58 patients movement disorder classification was revised, especially from ataxia and tremor to myoclonus. Differences in etiological diagnosis were particular made in the genetic domain where the confirmed genetic diagnosis in patients almost doubled from 17 to 32. The team changed the treatment strategy in the majority of the patients (60%). In 70% (n=40) patients and/or their caregivers reported a subjective positive effect three to six months after initiation. Conclusion The results of this observational study indicate that multidisciplinary specialist care significantly contributes to the diagnosis and treatment of young-onset movement disorders.

Reversal of Status Dystonicus after Relocation of Pallidal Electrodes in DYT6 Generalized Dystonia

Background DYT6 dystonia can have an unpredictable clinical course and the result of deep brain stimulation (DBS) of the internal part of the globus pallidus (GPi) is known to be less robust than in other forms of autosomal dominant dystonia. Patients who had previous stereotactic surgery with insufficient clinical benefit form a particular challenge with very limited other treatment options available. Case Report A pediatric DYT6 patient unexpectedly deteriorated to status dystonicus 1 year after GPi DBS implantation with good initial clinical response. After repositioning the DBS electrodes the status dystonicus resolved. Discussion This case study demonstrates that medication‐resistant status dystonicus in DYT6 dystonia can be reversed by relocation of pallidal electrodes. This case highlights that repositioning of DBS electrodes may be considered in patients with status dystonicus, especially when the electrode position is not optimal, even after an initial clinical response to DBS.