The changing face of reported status dystonicus - A systematic review.

BACKGROUND: Status Dystonicus (SD) represents the most severe end of the spectrum of dystonia. We aimed to explore whether reported features of cases of SD have changed over time. METHODS: A systematic review of cases of SD reported from 2017 to 2023 and comparison of features to data extracted from 2 previous literature reviews (epochs 2012-2017 and pre-2012). RESULTS: From 53 papers, a total 206 SD episodes in 168 patients were identified from 2017 to 2023. Combining data from all 3 epochs, a total of 339 SD episodes were reported from 277 patients. SD episodes occurred mostly in children, with a trigger identified in 63.4% of episodes, most commonly infection/inflammation. Most reported underlying aetiologies were genetic (e.g. 49.5% between 2017 and 2023), including new associated aetiologies in each epoch. Deep Brain Stimulation (DBS)-related SD increased over time. Neurosurgical interventions were more frequently reported in later epochs. Across the epochs, return to or improvement post SD episode, compared to baseline was reported above 70%. Reported mortality was 4.9% most recently, compared to 11.4% and 7.9%, previously. CONCLUSIONS: SD episodes reported have more than doubled in the last 5 years. Reports of medication change-induced SD have become less frequent, whilst episodes of DBS-related SD have become more frequent. More dystonia aetiologies, including novel aetiologies have been reported in recent cohorts, reflecting advances in genetic diagnosis. Neurosurgical interventions are increasingly reported in the management of SD episodes, including novel use of intraventricular baclofen. Overall outcomes from SD remain largely unchanged over time. No prospective epidemiological studies of SD were identified.

Spastic dystonia: Still a valid term.

Hypertonia in childhood may arise because of a variable combination of neuronal and non-neuronal factors. Involuntary muscle contraction may be due to spasticity or dystonia, which represent disorders of the spinal reflex arch and of central motor output respectively. Whilst consensus definitions for dystonia have been established, definitions of spasticity vary, highlighting the lack of a single unifying nomenclature in the field of clinical movement science. The term spastic dystonia refers to involuntary tonic muscle contraction in the context of an upper motor neuron (UMN) lesion. This review considers the utility of the term spastic dystonia, exploring our understanding of the pathophysiology of dystonia and the UMN syndrome. An argument is advanced that spastic dystonia is a valid construct that warrants further exploration. WHAT THIS PAPER ADDS: There is no single universally accepted definitions for terms commonly used to describe motor disorders. Spasticity and dystonia are phenomenologically and pathophysiologically distinct entities. Spastic dystonia represents a subset of dystonia, but with pathophysiological mechanisms more in common with spasticity.

Neurosurgical management of elevated tone in childhood: interventions, indications and uncertainties.

Elevated tone (hypertonia) is a common problem in children with physical disabilities. Medications intended to reduce tone often have limited efficacy, with use further limited by a significant side effect profile. Consequently, there has been growing interest in the application of Neurosurgical Interventions for the Management of Posture and Tone (NIMPTs). Three main procedures are now commonly used: selective dorsal rhizotomy (SDR), intrathecal baclofen (ITB) and deep brain stimulation (DBS). This review compares these interventions, along with discussion on the potential role of lesioning surgery. These interventions variably target spasticity and dystonia, acting at different points in the distributed motor network. SDR, an intervention for reducing spasticity, is most widely used in carefully selected ambulant children with cerebral palsy. ITB is more commonly used for children with more severe disability, typically non-ambulant, and can improve both dystonia and spasticity. DBS is an intervention which may improve dystonia. In children with certain forms of genetic dystonia DBS may dramatically improve dystonia. For other causes of dystonia, and in particular dystonia due to acquired brain injury, improvements following surgery are more modest and variable. These three interventions vary in terms of their side-effect profile and reversibility. There are currently populations of children for who it is unclear which intervention should be considered (SDR vs ITB, or ITB vs DBS). Concerns have been raised as to the equity of access to NIMPTs for children across the UK, and whether the number of surgeries performed each year meets the clinical need.

Metabolic patterns in brain 18F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia.

There is a lack of imaging markers revealing the functional characteristics of different brain regions in paediatric dystonia. In this observational study, we assessed the utility of [18F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in understanding dystonia pathophysiology by revealing specific resting awake brain glucose metabolism patterns in different childhood dystonia subgroups. PET scans from 267 children with dystonia being evaluated for possible deep brain stimulation surgery between September 2007 and February 2018 at Evelina London Children's Hospital (ELCH), UK, were examined. Scans without gross anatomical abnormality (e.g. large cysts, significant ventriculomegaly; n = 240) were analysed with Statistical Parametric Mapping (SPM12). Glucose metabolism patterns were examined in the 144/240 (60%) cases with the 10 commonest childhood-onset dystonias, focusing on nine anatomical regions. A group of 39 adult controls was used for comparisons. The genetic dystonias were associated with the following genes: TOR1A, THAP1, SGCE, KMT2B, HPRT1 (Lesch Nyhan disease), PANK2 and GCDH (Glutaric Aciduria type 1). The acquired cerebral palsy (CP) cases were divided into those related to prematurity (CP-Preterm), neonatal jaundice/kernicterus (CP-Kernicterus) and hypoxic-ischaemic encephalopathy (CP-Term). Each dystonia subgroup had distinct patterns of altered FDG-PET uptake. Focal glucose hypometabolism of the pallidi, putamina or both, was the commonest finding, except in PANK2, where basal ganglia metabolism appeared normal. HPRT1 uniquely showed glucose hypometabolism across all nine cerebral regions. Temporal lobe glucose hypometabolism was found in KMT2B, HPRT1 and CP-Kernicterus. Frontal lobe hypometabolism was found in SGCE, HPRT1 and PANK2. Thalamic and brainstem hypometabolism were seen only in HPRT1, CP-Preterm and CP-term dystonia cases. The combination of frontal and parietal lobe hypermetabolism was uniquely found in CP-term cases. PANK2 cases showed a distinct combination of parietal hypermetabolism with cerebellar hypometabolism but intact putaminal-pallidal glucose metabolism. HPRT1, PANK2, CP-kernicterus and CP-preterm cases had cerebellar and insula glucose hypometabolism as well as parietal glucose hypermetabolism. The study findings offer insights into the pathophysiology of dystonia and support the network theory for dystonia pathogenesis. 'Signature' patterns for each dystonia subgroup could be a useful biomarker to guide differential diagnosis and inform personalized management strategies.

Probabilistic mapping of deep brain stimulation in childhood dystonia.

OBJECTIVES: In adults with dystonia Probabilistic Stimulation Mapping (PSM) has identified putative "sweet spots" for stimulation. We aimed to apply PSM to a cohort of Children and Young People (CYP) following DBS surgery. METHODS: Pre-operative MRI and post-operative CT images were co-registered for 52 CYP undergoing bilateral pallidal DBS (n = 31 genetic/idiopathic dystonia, and n = 21 Cerebral Palsy (CP)). DBS electrodes (n = 104) were automatically detected, and Volumes of Tissue Activation (VTA) derived from individual patient stimulation settings. VTAs were normalised to the MNI105 space, weighted by percentage improvement in Burke-Fahn-Marsden Dystonia Rating scale (BFMDRS) at one-year post surgery and mean improvement was calculated for each voxel. RESULTS: For the genetic/idiopathic dystonia group, BFMDRS improvement was associated with stimulation across a broad volume of the GPi. A spatial clustering of the upper 25th percentile of voxels corresponded with a more delineated volume within the posterior ventrolateral GPi. The MNI coordinates of the centroid of this volume (X = -23.0, Y = -10.5 and Z = -3.5) were posterior and superior to the typical target for electrode placement. Volume of VTA overlap with a previously published "sweet spots" correlated with improvement following surgery. In contrast, there was minimal BFMDRS improvement for the CP group, no spatial clustering of efficacious clusters and a correlation between established "sweet spots" could not be established. CONCLUSIONS: PSM in CYP with genetic/idiopathic dystonia suggests the presence of a "sweet spot" for electrode placement within the GPi, consistent with previous studies. Further work is required to identify and validate putative "sweet spots" across different cohorts of patients.

Neurodisability care in the time of COVID-19.

BACKGROUND: The COVID-19 pandemic resulted in an unprecedented societal and healthcare global crisis. Associated changes in regular healthcare provision and lifestyle through societal lockdown are likely to have affected clinical management and well-being of children/young people with neurodisability, who often require complex packages of multidisciplinary care. METHODS: We surveyed 108 families of children/young people with severe physical neurodisability and multiple comorbidities to understand how the pandemic had affected acute clinical status, routine healthcare provision, schooling and family mental and social well-being. RESULTS: A significant proportion of families reported missing hospital appointments and routine therapy, with subsequent worsening of symptoms and function. Families additionally described worsening stress and anxiety during the pandemic, regardless of their baseline level of socio-economic deprivation. CONCLUSION: This highlights the profound effect of the COVID-19 pandemic on health and function in young people with severe neurodisabilities and emphasizes the clear need to better understand how to support this vulnerable population moving forwards.

Care in COVID: A qualitative analysis of the impact of COVID-19 on the health and care of children and young people with severe physical neurodisability and their families.

AIM: To evaluate clinicians' perspectives on the impact of 'lockdown' during the COVID-19 pandemic for children and young people with severe physical neurodisability and their families. METHOD: Framework analysis of comments from families during a recent service review was used to code the themes discussed according to the World Health Organization International Classification of Functioning, Disability and Health (ICF) and interpreted into emergent themes to summarize the impact of lockdown (Stage 1). They were presented to a clinician focus group for discussion (consultants and physiotherapists working in a specialist motor disorders service, [Stage 2]). RESULTS: Three overarching themes 'Uncertainty and Anxiety', 'Exacerbation of Existing Inequalities' and 'Care Provision: Reaction, Adaptation, and Innovation' summed up the impact of the COVID-19 pandemic on health and well-being in children and young people with neurodisability and their families. All themes were influenced by time. INTERPRETATION: This study reflects clinician's perceptions of family experiences of the pandemic and lockdown. Significant impact is apparent in the entire U.K. population, but the complexity of care needs for children with physical neurodisability exacerbates this. Lobbying for government policy is vital to ensure that all children, and in particular those with significant health and social care needs, are protected and continue to access services. During the restoration and recovery phase of the pandemic, there is a need for service reconfiguration that utilizes what we have learned and is adaptive to individual family circumstances.

Intrathecal baclofen pumps in the management of hypertonia in childhood: a UK and Ireland wide survey.

BACKGROUND: Intrathecal baclofen (ITB) is a useful treatment for hypertonia where non-invasive treatments have been ineffective or poorly tolerated. There is an absence of national guidance on selection criteria and a lack of literature regarding patient characteristics and treatment details for children and young people (CYP) receiving ITB therapy in the UK and Ireland. We aimed to gather patient and treatment characteristics for CYP receiving ITB in the UK and Ireland. METHODS: An electronic survey was sent to all paediatric ITB centres in the UK and Ireland. Anonymised data were returned between December 2019 and April 2020. CYP >16 years and those awaiting ITB pump removal were excluded from the dataset. RESULTS: 176 CYP were identified as receiving ITB therapy across the UK and Ireland. The majority of CYP with ITB pumps were non-ambulant (93%) with a diagnosis of cerebral palsy (79%). Median age of ITB insertion was 9 years; median current age was 14 years. 79% of CYP had significant spasticity, 55% had significant dystonia. The most commonly used ITB dosing modes were continuous (73%) and flexible (23%). CONCLUSIONS: ITB pumps were most frequently used for non-ambulant CYP with cerebral palsy and existence of spasticity and/or dystonia in the UK and Ireland. Most CYP were receiving a continuous dose of ITB. There is significant variation in the number of paediatric ITB pumps across UK and Ireland. There is a need for development of nationally accepted paediatric referral criteria and clinical standards for ITB use.

Rett Syndrome as a movement and motor disorder - A narrative review.

Rett syndrome (RTT) is neurodevelopmental disorder affecting approximately 1:10000-15000 live female births, commonly associated with MECP2 gene mutations. Hand stereotypies and gait disturbance, as well as spasticity and dystonia, were noted in RTT since first descriptions. This review aimed to explore the prevalence of reported movement disorders in RTT. DATA SOURCES AND EXTRACTION: Pubmed and Embase databases for papers describing features of movement disorders in RTT. Papers were selected if included description of case report, cohort or case-series of patients with RTT including descriptions of clinical features of their movement disorder. Papers were divided into 3 epochs - i) Pre-1999,ii) 2000-2009, and iii) 2010 onwards. RESULTS: 32 studies (13 in the first, 10 in the second and 9 in the third epochs) reported on movement disorders in RTT. Hand stereotypies were almost universal, diminishing but not disappearing over time. Gait disturbance and ataxia/tremor were also very common (>50% cases). Hypertonia was also often reported, increasing with age. In earlier descriptions spasticity was commonly described, with greater reference to dystonia/rigidity in more recent reports. Myoclonus and choreoathetosis were uncommonly reported. CONCLUSIONS: Movement disorders beyond hand stereotypies are common in RTT, most notably tremor. Hypertonia is frequently seen in RTT, increasing in prevalence with age, with apparent changes in nomenclature over time, (i.e early epoch spasticity, late epoch dystonia). Dystonia was specifically reported in 229/417 cases. Further work is required to explore the relative contribution of dystonia and rigidity to hypertonia in RTT, as well as the impact of these impairments when present.

Deep brain stimulation reduces pain in children with dystonia, including in dyskinetic cerebral palsy.

AIM: To establish the prevalence of dystonic pain in children and their response to deep brain stimulation (DBS). METHOD: Dystonic pain was assessed in a cohort of 140 children, 71 males and 69 females, median age 11 years 11 months (range 3y-19y 1mo), undergoing DBS in our centre over a period of 10 years. The cohort was divided into aetiological dystonia groups: 1a, inherited; 1b, heredodegenerative; 2, acquired; and 3, idiopathic. Motor responses were measured with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: Dystonic pain was identified in 63 (45%) patients, 38% of whom had a diagnosis of cerebral palsy (CP). Dystonic pain improved in 90% of children and in all aetiological subgroups 1 year after DBS, while the BFMDRS motor score improved in 70%. Statistically significant improvement (p<0.01) was noted for the whole cohort on the Numerical Pain Rating Scale (n=27), Paediatric Pain Profile (n=17), and Caregivers Priorities and Child Health Index of Life with Disabilities questionnaire (n=48). There was reduction of pain severity, frequency, and analgesia requirement. Findings were similar for the whole cohort and aetiological subgroups other than the inherited heredodegenerative group where the improvement did not reach statistical significance. INTERPRETATION: Dystonic pain is frequent in children with dystonia, including those with CP, who undergo DBS; this can be an important, realizable goal of surgery irrespective of aetiology. We encourage the use of multimodal approach in pain research to reduce the risk of bias.

Fifteen-minute consultation: A clinical approach to the management of the child with hypertonia.

Elevated tone (hypertonia) is a common problem seen in the paediatric clinic. For most children and young people, hypertonia is just one aspect of a broader disorder of movement and posture. This paper describes a clinical approach to the management of hypertonia in children, considering the contribution of high tone to the functional problems experienced by the child, the potential adverse effects of reducing tone, side effects of the intervention and the importance of setting objectives/goals for intervention which can be measured at follow-up. We describe this as the 'MOTOR' approach and provide some examples of how it can be used in practice.