Clinical Presentation of Spasticity and Passive Range of Motion Deviations in Dyskinetic Cerebral Palsy in Relation to Dystonia, Choreoathetosis, and Functional Classification Systems.

Objectives: To map the presence, severity, and distribution of spasticity and passive range of motion (pROM) deviations in dyskinetic cerebral palsy (DCP), and to explore their relation with dystonia, choreoathetosis, and functional abilities.Methods: This cross-sectional study included 53 participants with DCP. Spasticity was assessed with the Modified Ashworth Scale, limited- and increased pROM (hypermobility) with a goniometer, dystonia and choreoathetosis with the Dyskinesia Impairment Scale, gross motor and manual abilities with corresponding functional classification systems.Results: Spasticity and limited pROM were correlated with dystonia of the upper limbs (0.41< rs<0.47, <0.001 < p < .002) and lower limbs (0.31< rs<0.41, 0.002 < p < .025), and both functional systems of gross motor (0.32< rs<0.51, <0.001 < p < .018) and fine manual abilities (0.34< rs<0.44, 0.001 < p < .014). Hypermobility is correlated only with choreoathetosis of the lower limbs (0.44, p = .001).Conclusions: Coexisting spasticity and pROM deviations in DCP are functionally limiting and should be addressed accordingly. Hypermobility may lead to an increased luxation risk.

Treatment of Paroxysmal Dyskinesia.

Paroxysmal dyskinesia (PxD) is a heterogeneous group of syndromes characterized by recurrent attacks of abnormal movements, triggered by detectable factors, without loss of consciousness. According to the precipitating factors, they are classified as paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dystonia (PED). PxD treatment is based on the combination of nonpharmacologic and pharmacologic approaches. Pharmacologic and nonpharmacologic treatments effective for PNKD and PED also are available. In PxD refractory to conventional treatment, surgery might be an alternative therapeutic option. The course of PRRT2-PKD and MR-1-PNKD is benign, and treatment might not be needed with advancing age.

Functional gait disorders, clinical phenomenology, and classification.

BACKGROUND: Functional gait disorders (FGDs) are relatively common in patients presenting for evaluation of a functional movement disorder (FMD). The diagnosis and classification of FGDs is complex because patients may have a primary FGD or a FMD interfering with gait. METHODS: We performed a detailed evaluation of clinical information and video recordings of gait in patients diagnosed with FMDs. RESULTS: We studied a total of 153 patients with FMDs, 68% females, with a mean age at onset of 36.4 years. A primary FGD was observed in 39.2% of patients; among these patients, 13 (8.5%) had an isolated FGD (a gait disorder without other FMDs). FMDs presented in 34% of patients with otherwise normal gait. Tremor was the most common FMD appearing during gait, but dystonia was the most common FMD interfering with gait. Patients with FGD had a higher frequency of slow-hesitant gait, astasia-abasia, bouncing, wide-based gait and scissoring compared with patients with FMDs occurring during gait. Bouncing gait with knee buckling was more frequently observed in patients with isolated FGD (P = 0.017). Patients with FGDs had a trend for higher frequency of wheelchair dependency (P = 0.073) than those with FMDs interfering with gait. CONCLUSIONS: Abnormal gait may be observed as a primary FGD or in patients with other FMDs appearing during gait; both conditions are common and may cause disability.

[Dystonia].

This review presents the newest classification of dystonia, new evidence regarding aetiology, the diagnosis of dystonia, and the most common forms of treatment. Dystonia is a rare and heterogeneous movement disorder defined as a syn-drome of sustained muscle contractions with twisting and abnormal postures, and tremor. Dystonia is a collective term for different syndromes, primary idiopathic forms as well as genetic and secondary forms.

Clinical approach to tremor in children.

Pediatric Movement Disorders encompass a very large and complex group of diseases, among which Tremor is one of the least studied. Evaluation of tremors in kids carries significant challenges, in particular the fact that many tremor etiologies have other associated movement disorders that make tremor identification more difficult. Also, it is sometimes difficult to differentiate tremors from other shaking disorders. Yet, the correct identification of tremor leads to appropriate treatments and sometimes practical cures. Thus, in this paper we have strived to provide a succinct, clinically useful and practical review of pediatric tremors. The most useful classification of tremors in based on their predominance during rest or activity. By far, the most common tremor in children is during action. We provide a clinical algorithm on how to assess pediatric tremors at the bedside, as well as multiple useful tables. We also review common tremor etiologies.

Dystonia.

Dystonia is a neurological condition characterized by abnormal involuntary movements or postures owing to sustained or intermittent muscle contractions. Dystonia can be the manifesting neurological sign of many disorders, either in isolation (isolated dystonia) or with additional signs (combined dystonia). The main focus of this Primer is forms of isolated dystonia of idiopathic or genetic aetiology. These disorders differ in manifestations and severity but can affect all age groups and lead to substantial disability and impaired quality of life. The discovery of genes underlying the mendelian forms of isolated or combined dystonia has led to a better understanding of its pathophysiology. In some of the most common genetic dystonias, such as those caused by TOR1A, THAP1, GCH1 and KMT2B mutations, and idiopathic dystonia, these mechanisms include abnormalities in transcriptional regulation, striatal dopaminergic signalling and synaptic plasticity and a loss of inhibition at neuronal circuits. The diagnosis of dystonia is largely based on clinical signs, and the diagnosis and aetiological definition of this disorder remain a challenge. Effective symptomatic treatments with pharmacological therapy (anticholinergics), intramuscular botulinum toxin injection and deep brain stimulation are available; however, future research will hopefully lead to reliable biomarkers, better treatments and cure of this disorder.

Characteristics of two distinct clinical phenotypes of functional (psychogenic) dystonia: follow-up study.

BACKGROUND: The fixed dystonia phenotype was originally established as a prototype of functional dystonia. Nevertheless, in recent reports different functional dystonia phenotypes have been recognized with dystonic movement comprising phasic instead of tonic contraction. OBJECTIVES: To examine clinical characteristic in all patients with dystonia who fulfilled the criteria for functional movement disorders irrespective of phenotype in an attempt to determine parameters of clinical presentations that might impact the disease progression pattern and outcome. METHODS: Patients presented with dystonia features incompatible with organic disease without other features required for the diagnosis of functional movement disorders were analyzed and prospectively followed-up. The two-step cluster analysis was performed to obtain the subgroups of dystonia phenotypes. RESULTS: The two-step cluster analysis extracted two subgroup of patients. Patients of the first cluster (68.8%) presented with "mobile" dystonia (84.9%), of cranial/neck/trunk localization (90.9%), fluctuated clinical course (69.7%), with frequent additional movement or other functional neurological disorders (63.6%) during follow-up. In the second cluster (31.2%) all of the patients presented with "fixed" dystonia of extremities, and the clinical course was characterized by either the disease progression (60%), or continuous without improvement (26.7%), and rare occurrence of additional functional neurological disorders (13.3%). CONCLUSION: In terms of clinical and demographic features as well as pattern of disease progression there are two clinical phenotypes in patients with functional dystonia. Distinctive features of incongruence and inconstancy are characteristic for "mobile" functional dystonia subgroup of patients.

Identification and measurement of dystonia in cerebral palsy.

AIM: To establish the prevalence and severity of dystonia in a population of children with cerebral palsy (CP) with hypertonia assessment and measurement tools. METHOD: A cross-sectional study of 151 children (84 males, 67 females) with CP who were assessed with the Hypertonia Assessment Tool (HAT) and Barry-Albright Dystonia scale (BAD) for identification and measurement of severity of dystonia. HAT dystonia items were assessed for construct and convergent validity. RESULTS: Distribution by predominant motor type (PMT) was: 85% spastic, 14% dyskinetic, and 1% ataxic. Spastic and dyskinetic groups showed widespread evidence of dystonia according to HAT profiles and BAD scores. The dyskinetic PMT group had a higher mean BAD score than the spastic group (difference of 13 units, 95% CI 9.1-16.4). Dystonia severity (BAD score) increased linearly across gross motor (p<0.001), manual ability (p<0.001) and communication functional levels (p<0.001). Divergence was noted in how HAT item six identified dystonia compared to items one and two. INTERPRETATION: The HAT provided an estimate of the prevalence of both spasticity and dystonia in a large CP population, beyond predominant motor type. Dystonia is a common finding in the spastic PMT group, and its severity increases as motor function worsens. WHAT THIS PAPER ADDS: Dystonia is readily identified in cerebral palsy (CP) using the Hypertonia Assessment Tool, regardless of the predominant motor type. Spasticity and dystonia frequently coexist in the CP population. Severity of dystonia is inversely related to motor function.

Clinical Management of Dystonia in Childhood.

Dystonia is one of the most frequent movement disorders in childhood. It can impede normal motor development and cause significant motor disability. The diagnostic evaluation of childhood dystonia is challenging due to the phenotypic variability and heterogeneous etiologies. Evidence to guide the diagnostic evaluation and treatment is limited. Assessment is primarily directed by clinical history and distinctive examination findings. Neuroimaging is typically necessary to evaluate for acquired or complex inherited dystonias. A trial of levodopa can be both diagnostic and therapeutic in children with dopa-responsive dystonia. However, for the majority of children with early-onset dystonia, treatment is symptomatic with varying efficacy. There is a paucity of therapeutic trials for childhood dystonia and most treatment recommendations are consensus or expert opinion driven. This review summarizes the available evidence and guidelines on the diagnostic evaluation and pharmacological treatment of childhood-onset dystonia and provides practical frameworks to approach both issues based on best evidence.

The International Classification of Functioning (ICF) to evaluate deep brain stimulation neuromodulation in childhood dystonia-hyperkinesia informs future clinical & research priorities in a multidisciplinary model of care.

The multidisciplinary team (MDT) approach illustrates how motor classification systems, assessments and outcome measures currently available have been applied to a national cohort of children and young people with dystonia and other hyperkinetic movement disorders (HMD) particularly with a focus on dyskinetic cerebral palsy (CP). The paper is divided in 3 sections. Firstly, we describe the service model adopted by the Complex Motor Disorders Service (CMDS) at Evelina London Children's Hospital and King's College Hospital (ELCH-KCH) for deep brain stimulation. We describe lessons learnt from available dystonia studies and discuss/propose ways to measure DBS and other dystonia-related intervention outcomes. We aim to report on current available functional outcome measures as well as some impairment-based assessments that can encourage and generate discussion among movement disorders specialists of different backgrounds regarding choice of the most important areas to be measured after DBS and other interventions for dystonia management. Finally, some recommendations for multi-centre collaboration in regards to functional clinical outcomes and research methodologies for dystonia-related interventions are proposed.

Classification of dystonia in childhood.

OBJECTIVE: The most recent international consensus update on dystonia classification proposed a system based on 2 axes, clinical characteristics and aetiology. We aimed to apply this system to Children and Young People (CAYP) selected for movement disorder surgery, and determine if meaningful groupings of cases could be extracted. METHODS: The 2013 Consensus Committee classification system for dystonia was retrospectively applied to 145 CAYP with dystonic movement disorders. Two-step cluster analysis was applied to the resulting categorisations to identify groupings of CAYP with similar characteristics. RESULTS: Classification resulted in a total of 43 unique groupings of categorisation. Cluster analysis detected 4 main clusters of CAYP, comparable to previously used patient groupings. CONCLUSIONS: The 2013 consensus update on dystonia classification can be applied to CAYP with dystonia. The large number of categories provides a wealth of information for the clinician, and also facilitates data driven grouping into clinically meaningful subgroups.

Frequency-Specific Local Synchronization Changes in Paroxysmal Kinesigenic Dyskinesia.

The neurobiological basis of paroxysmal kinesigenic dyskinesia (PKD) is poorly defined due to the lack of reliable neuroimaging differences that can distinguish PKD with dystonia (PKD-D) from PKD with chorea (PKD-C). Consequently, diagnosis of PKD remains largely based on the clinical phenotype. Understanding the pathophysiology of PKD may facilitate discrimination between PKD-D and PKD-C, potentially contributing to more accurate diagnosis. We conducted resting-state functional magnetic resonance imaging on patients with PKD-D (n = 22), PKD-C (n = 10), and healthy controls (n = 32). Local synchronization was measured in all 3 groups via regional homogeneity (ReHo) and evaluated using receiver operator characteristic analysis to distinguish between PKD-C and PKD-D. Cortical-basal ganglia circuitry differed significantly between the 2 groups at a specific frequency. Furthermore, the PKD-D and PKD-C patients were observed to show different spontaneous brain activity in the right precuneus, right putamen, and right angular gyrus at the slow-5 frequency band (0.01-0.027 Hz). The frequency-specific abnormal local synchronization between the 2 types of PKD offers new insights into the pathophysiology of this disorder to some extent.

Burke-Fahn-Marsden dystonia severity, Gross Motor, Manual Ability, and Communication Function Classification scales in childhood hyperkinetic movement disorders including cerebral palsy: a 'Rosetta Stone' study.

AIM: Hyperkinetic movement disorders (HMDs) can be assessed using impairment-based scales or functional classifications. The Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) evaluates dystonia impairment, but may not reflect functional ability. The Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) are widely used in the literature on cerebral palsy to classify functional ability, but not in childhood movement disorders. We explore the concordance of these three functional scales in a large sample of paediatric HMDs and the impact of dystonia severity on these scales. METHOD: Children with HMDs (n=161; median age 10y 3mo, range 2y 6mo-21y) were assessed using the BFM-M, GMFCS, MACS, and CFCS from 2007 to 2013. This cross-sectional study contrasts the information provided by these scales. RESULTS: All four scales were strongly associated (all Spearman's rank correlation coefficient rs >0.72, p<0.001), with worse dystonia severity implying worse function. Secondary dystonias had worse dystonia and less function than primary dystonias (p<0.001). A longer proportion of life lived with dystonia is associated with more severe dystonia (rs =0.42, p<0.001). INTERPRETATION: The BFM-M is strongly linked with the GMFCS, MACS, and CFCS, irrespective of aetiology. Each scale offers interrelated but complementary information and is applicable to all aetiologies. Movement disorders including cerebral palsy can be effectively evaluated using these scales.

Non-motor symptoms in genetically defined dystonia: Homogenous groups require systematic assessment.

INTRODUCTION: Dystonia is a movement disorder involving sustained or intermittent muscle contractions resulting in abnormal movements and postures. Identification of disease causing genes has allowed examination of genetically homogenous groups. Unlike the motor symptoms, non-motor characteristics are less clearly defined, despite their impact on a patient's quality of life. This review aims to examine the evidence for non-motor symptoms, addressing cohort size and methods of assessment in each study. METHODS: A systematic and standardised search strategy was used to identify the published literature relating to psychiatric symptoms, cognition, sleep disorders, sensory abnormalities and pain in each of the genetically determined dystonias. Studies were divided according to cohort size, method of assessment and whether comparison was made to an appropriate control group. RESULTS: Ninety-five articles were identified including reported clinical histories (n = 42), case reports and smaller case series (n = 12), larger case series (n = 23) and case-control cohorts (n = 18). Psychiatric symptoms were the most frequently investigated with anxiety, depression and Obsessive-Compulsive disorder being most common. Cognitive impairment involved either global deficits or isolated difficulties in specific domains. Disturbances to sleep were most common in the dopa-responsive dystonias. Sensory testing in DYT1 cases identified an intermediate subclinical phenotype. CONCLUSION: Non-motor symptoms form an integral component of the dystonia phenotype. However, future studies should involve a complete assessment of all symptom subtypes in order to understand the frequency and gene-specificity of these symptoms. This will enable early symptom identification, appropriate clinical management, and provide additional outcome measures in future clinical trials.

Recent developments in dystonia.

PURPOSE OF REVIEW: The dystonias are a family of related disorders with many different clinical manifestations and causes. This review summarizes recent developments regarding these disorders, focusing mainly on advances with direct clinical relevance from the past 2 years. RECENT FINDINGS: The dystonias are generally defined by their clinical characteristics, rather than by their underlying genetic or neuropathological defects. The many varied clinical manifestations and causes contribute to the fact that they are one of the most poorly recognized of all movement disorders. A series of recent publications has addressed these issues, offering a revised definition and more logical means for classifying the many subtypes. Our understanding of the genetic and neurobiological mechanisms responsible for different types of dystonias also has grown rapidly, creating new opportunities and challenges for diagnosis, and identifying increasing numbers of rare subtypes for which specific treatments are available. SUMMARY: Recent advances in describing the clinical phenotypes and determining associated causes have pointed to the need for new strategies for diagnosis, classification, and treatment of the dystonias.

The genetics of the dystonias--a review based on the new classification of the dystonias.

The definition and classification of the dystonias was recently revisited. In the new 2013 classification, the dystonias are subdivided in terms of their etiology according to whether they are the result of pathological changes or structural damage, have acquired causes or are inherited. As hereditary dystonias are clinically and genetically heterogeneous, we sought to classify them according to the new recently defined criteria. We observed that although the new classification is still the subject of much debate and controversy, it is easy to use in a logical and objective manner with the inherited dystonias. With the discovery of new genes, however, it remains to be seen whether the new classification will continue to be effective.

The genetics of the dystonias – a review based on the new classification of the dystonias / A genética das distonias – uma revisão baseada na nova classificação das distonias

The definition and classification of the dystonias was recently revisited. In the new 2013 classification, the dystonias are subdivided in terms of their etiology according to whether they are the result of pathological changes or structural damage, have acquired causes or are inherited. As hereditary dystonias are clinically and genetically heterogeneous, we sought to classify them according to the new recently defined criteria. We observed that although the new classification is still the subject of much debate and controversy, it is easy to use in a logical and objective manner with the inherited dystonias. With the discovery of new genes, however, it remains to be seen whether the new classification will continue to be effective.

O conceito e a classificação das distonias foram recentemente revisados. Na nova classificação de 2013, quanto à etiologia, as distonias podem ser subdividas em relação às alterações patológicas, aos danos estruturais, às causas adquiridas e à hereditariedade. Como as distonias hereditárias são clínica e geneticamente heterogêneas, buscamos classifica-las segundo os novos critérios estabelecidos recentemente. Observamos que apesar da nova classificação das distonias ainda ser objeto de discussões e controvérsias, ela pode usada com facilidade, de uma maneira lógica e objetiva, no contexto das distonias hereditárias. Com a descoberta de novos genes poderemos observar se essa classificação continuará sendo efetiva.