Anouk Kuiper

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.

Myoclonus in childhood-onset neurogenetic disorders: The importance of early identification and treatment

BACKGROUND In clinical practice, myoclonus in childhood-onset neurogenetic disorders frequently remains unrecognized, because it is often overshadowed by other neurological features. Since treatment can lead to significant functional improvement, accurate phenotyping is essential. To demonstrate the importance of early identification and treatment, we report on four patients with various childhood-onset neurogenetic disorders suffering from myoclonus. METHODS We evaluated four patients with established childhood-onset neurogenetic disorders and involuntary jerky movements, who visited our young-onset movement disorder outpatient clinic. RESULTS We present the clinical data of four patients (aged 8-21 years) with childhood-onset neurogenetic disorders, including ataxia-telangiectasia, Coffin-Lowry syndrome and epileptic encephalopathy due to SCN1A mutations. All four suffered from jerky movements that hampered normal daily activities and that had gone unrecognized for several years. The presence of multifocal myoclonus was confirmed by polymyography. In all patients, treatment resulted in marked improvement of both myoclonus and overall functioning. CONCLUSION These cases highlight the relevance of actively searching for myoclonus in childhood-onset neurogenetic disorders, even when a molecular diagnosis has already been established. To further improve the awareness and recognition of myoclonus in children, we provide a list of childhood-onset neurogenetic disorders with myoclonus as important associated feature.

Serotonergic perturbations in dystonia disorders a systematic review

Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent muscle contractions. Emerging data describe high prevalences of non-motor symptoms, including psychiatric co-morbidity, as part of the phenotype of dystonia. Basal ganglia serotonin and serotonin-dopamine interactions gain attention, as imbalances are known to be involved in extrapyramidal movement and psychiatric disorders. We systematically reviewed the literature for human and animal studies relating to serotonin and its role in dystonia. An association between dystonia and the serotonergic system was reported with decreased levels of 5-hydroxyindolacetic acid, the main metabolite of serotonin. A relation between dystonia and drugs affecting the serotonergic system was described in 89 cases in 49 papers. Psychiatric co-morbidity was frequently described, but likely underestimated as it was not systematically examined. Currently, there are no good (pharmaco)therapeutic options for most forms of dystonia or associated non-motor symptoms. Further research using selective serotonergic drugs in appropriate models of dystonia is required to establish the role of the serotonergic system in dystonia and to guide us to new therapeutic strategies.

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.

Cortical Myoclonus in a Young Boy with GOSR2 Mutation Mimics Chorea

Myoclonus can resemble other abrupt movements, such as chorea. The clinical distinction can be challenging, particularly at a young age. Myoclonus is defined as sudden, brief, shocklike involuntary movements caused by muscular contractions or inhibitions. Chorea is a nonpatterned, involuntary movement disorder with continuous movements, variable in speed, unpredictable in timing and direction, and flowing or jerky in appearance. Especially, the jerky components of chorea may be difficult to distinguish from myoclonus. Here, we present the case of a young boy with hyperkinetic movements closely resembling chorea. EEG/electromyography (EMG) recordings showed cortical reflex myoclonus. This case demonstrates that myoclonus in young patients with GOSR2 mutations can mimic chorea.

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.

The frequency and self-perceived impact on daily life of motor and non-motor symptoms in cervical dystonia

Evidence suggests that non‐motor symptoms (NMS) are the most important predictors of decreased health‐related quality of life (HR‐QoL) in patients with cervical dystonia (CD). In this study, we evaluate an NMS screening list and examine the influence of motor symptoms and NMS on HR‐QoL.

Clinical Pearls - how my patients taught me: The fainting lark symptom

BackgroundCompulsive movements, complex tics and stereotypies are frequent, especially among patients with autism or psychomotor retardation. These movements can be difficult to characterize and can mimic other conditions like epileptic seizures or paroxysmal dystonia, particularly when abnormal breathing and cerebral hypoxia are induced.Case presentationWe describe an 18-year-old patient with Asperger syndrome who presented with attacks of tonic posturing of the trunk and neck. The attacks consisted of self-induced stereotypic stretching of the neck combined with a compulsive Valsalva-like maneuver. This induced cerebral hypoperfusion and subsequently dysautonomia and some involuntary movements of the arms.ConclusionThis patient suffered from a complex tic with compulsive respiratory stereotypies. His symptoms contain aspects of a phenomenon described in early literature as ‘the fainting lark’.

Case StudyPatience is the key: Contraceptive induced chorea in a girl with Down Syndrome

BACKGROUND Isolated (sub)acute chorea in young patients is a relatively rare movement disorder with a broad differential diagnosis, including drug-induced, post-infectious, auto-immunological and vascular aetiologies. CASE PRESENTATION We describe an adolescent girl with Downs syndrome presenting with chorea due to oral contraceptive usage. After discontinuation of the oral contraceptive it took several months before the symptoms disappeared. Although generally well recognised, it is important to realise this delayed effect. Rejecting the diagnosis too soon may lead to unnecessary treatment for other possible underlying aetiologies, especially in patients with Down Syndrome, known to be vulnerable for autoimmune disorders. CONCLUSION We plead for discontinuation for at least three months before exclusion of oral contraceptives as cause of chorea.

Patience is the key: Contraceptive induced chorea in a girl with Down Syndrome

BACKGROUND Isolated (sub)acute chorea in young patients is a relatively rare movement disorder with a broad differential diagnosis, including drug-induced, post-infectious, auto-immunological and vascular aetiologies. CASE PRESENTATION We describe an adolescent girl with Downs syndrome presenting with chorea due to oral contraceptive usage. After discontinuation of the oral contraceptive it took several months before the symptoms disappeared. Although generally well recognised, it is important to realise this delayed effect. Rejecting the diagnosis too soon may lead to unnecessary treatment for other possible underlying aetiologies, especially in patients with Down Syndrome, known to be vulnerable for autoimmune disorders. CONCLUSION We plead for discontinuation for at least three months before exclusion of oral contraceptives as cause of chorea.