Rehabilitation after paediatric acquired brain injury: Longitudinal change in content and effect on recovery.

AIM: To describe cross-sectional and longitudinal variation in neurorehabilitation content provided to young people after severe paediatric acquired brain injury (pABI) and to relate this to observed functional recovery. METHOD: This was an observational study in a cohort of admissions to a residential neurorehabilitation centre. Recovery was described using the Pediatric Evaluation of Disability - Computer Adaptive Testing instrument. Rehabilitation content was measured using the recently described Paediatric Rehabilitation Ingredients Measure (PRISM) and examined using multidimensional scaling. RESULTS: The PRISM reveals wide variation in rehabilitation content between and during admissions primarily reflecting proportions of child active practice, child emotional support, and other management of body structure and function. Rehabilitation content is predicted by pre-admission recovery, suggesting therapist decisions in designing rehabilitation programmes are shaped by their initial expectations of recovery. However, significant correlations persist between plausibly-related aspects of delivered therapy and observed post-admission recovery after adjusting for such effects. INTERPRETATION: The PRISM approach to the analysis of rehabilitation content shows promise in that it demonstrates significant correlations between plausibly-related aspects of delivered therapy and observed recovery that have been hard to identify with other approaches. However, rigorous, causal analysis will be required to truly understand the contributions of rehabilitation to recovery after pABI. WHAT THIS PAPER ADDS: Rehabilitation content varies widely between, and during, admissions for neurorehabilitation after paediatric acquire brain injury. Strong correlations are seen between plausibly-related aspects of rehabilitation content and observed recovery, though careful interpretation is necessary.

Rasch Properties of the Cognitive and Linguistic Scale and Optimization for Outcome Trajectory Modeling in Pediatric Acquired Brain Injury.

OBJECTIVES: To (1) determine if items on the Cognitive and Linguistic Scale (CALS) follow a Rasch distribution and (2) explore the relationship between Rasch-derived Cognitive Ability Estimates and outcome trajectory parameters using a nonlinear mixed-effects modeling approach. DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation hospital. PARTICIPANTS: A total of 252 children (N=252) aged of 2-21 years (median, 11.8 [IQR, 6.4-15.9] years) consecutively admitted to an inpatient rehabilitation brain injury unit (2008-2014) for a first inpatient admission after acquired brain injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rasch-derived Cognitive Ability Estimates from the CALS and associated outcome trajectory parameters. RESULTS: The CALS demonstrates adequate interval-scale properties with removal of scores from the arousal and responsivity items. Rasch-derived Cognitive Ability Estimates were associated with age (ß=0.025, P<.001) such that older age was associated with a faster rate of recovery and more complete ultimate recovery. Slower recovery initiation was associated with a less complete overall cognitive recovery (Spearman ρ=-0.31; P<.001). CONCLUSIONS: The Cognitive Ability Estimates derived from the CALS and associated outcome parameters (eg, rate of recovery) may serve as an ideal outcome measure for clinical trials evaluating interventions for acquired brain injury in a pediatric rehabilitation setting.

Paediatric traumatic brain injury.

PURPOSE OF REVIEW: To provide a summary of recent developments in the field of paediatric traumatic brain injury (TBI). RECENT FINDINGS: The epidemiology of paediatric TBI with falling rates of severe TBI, and increasing presentations of apparently minor TBI. There is growing interest in the pathophysiology and outcomes of concussion in children, and detection of 'significant' injury, arising from concern about risks of long-term chronic traumatic encephalopathy. The role of decompressive craniectomy in children is still clarifying. SUMMARY: Paediatric TBI remains a major public health issue.

Structural connectivity in a paediatric case of anarchic hand syndrome.

BACKGROUND: "Anarchic hand" is a rare condition characterised by non-volitional, goal-directed movements of one arm. We report a case with analysis of structural and functional connectivity. CASE PRESENTATION: A 15 year old girl developed intermittent symptoms of intermanual conflict or anarchic hand as a result of traumatic brain injury during which she sustained a callosal bleed. Resting-state fMRI and DTI tractography were performed at a stage when symptoms had largely resolved. CONCLUSION: Structural connectivity between homologous superior frontal areas and functional connectivity between homologous posterior cingulate areas were significantly reduced, which may have contributed to causation. Tractography demonstrated new indirect connections between supplementary motor areas via the cerebellum, which we propose contributed to symptom resolution.

Routine intracranial pressure monitoring in acute coma.

BACKGROUND: We know that the brain damage resulting from traumatic and other insults is not due solely to the direct consequences of the primary injury. A significant and potentially preventable contribution to the overall morbidity arises from secondary hypoxic-ischaemic damage. Brain swelling accompanied by raised intracranial pressure (ICP) prevents adequate cerebral perfusion with well-oxygenated blood.Detection of raised ICP could be useful in alerting clinicians to the need to improve cerebral perfusion, with consequent reductions in brain injury. OBJECTIVES: To determine whether routine ICP monitoring in severe coma of any cause reduces the risk of all-cause mortality or severe disability at final follow-up. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL Plus, ISI Web of Science (SCI-EXPANDED & CPCI-S), clinical trials registries and reference lists. We ran the most recent search on 22 May 2015. SELECTION CRITERIA: All randomised controlled studies of real-time ICP monitoring by invasive or semi-invasive means in acute coma (traumatic or non-traumatic aetiology) versus clinical care without ICP monitoring (that is, guided only by clinical or radiological inference of the presence of raised ICP). DATA COLLECTION AND ANALYSIS: Two authors (ET and RF) worked independently to identify the one study that met inclusion criteria. JR and RF independently extracted data and assessed risk of bias. We contacted study authors for additional information, including details of methods and outcome data. MAIN RESULTS: One randomized controlled trial (RCT) meeting the selection criteria has been identified to date.The included study had 324 participants. We judged risk of bias to be low for all categories except blinding of participants and personnel, which is not feasible for this intervention. There were few missing data, and we analysed all on an intention-to-treat basis.Participants could be 13 years of age or older (mean age of sample 29; range 22 to 44), and all had severe traumatic brain injury, mostly due to traffic incidents. All were receiving care within intensive care units (ICUs) at one of six hospitals in either Bolivia or Ecuador. Investigators followed up 92% of participants for six months or until death. The trial excluded patients with a Glasgow Coma Score (GCS) less than three and fixed dilated pupils on admission on the basis that they had sustained brain injury of an unsalvageable severity.The study compared people managed using either an intracranial monitor or non-invasive monitoring (imaging and clinical examination) to identify potentially harmful raised intracranial pressure. Both study groups used imaging and clinical examination measures.Mortality at six months was 56/144 (39%) in the ICP-monitored group and 67/153 (44%) in the non-invasive group.Unfavourable outcome (defined as death or moderate to severe disability at six months) as assessed by the extended Glasgow Outcome Scale (GOS-E) was 80/144 (56%) in the ICP-monitored group and 93/153 (61%) in the non-invasive group.Six percent of participants in the ICP monitoring group had complications related to the monitoring, none of which met criteria for being a serious adverse event. There were no complications relating to the non-invasive group.Other complications and adverse events were comparable between treatment groups, 70/157 (45%) in the ICP-monitored group and 76/167 (46%) in the non-invasive group.Late mortality in both the monitored and non-invasive groups was high, with 35% of deaths occurring > 14 days after injury. The authors comment that this high late mortality may reflect inadequacies in post-ICU services for disabled survivors requiring specialist rehabilitation care. AUTHORS' CONCLUSIONS: The data from the single RCT studying the role of routine ICP monitoring in acute traumatic coma fails to provide evidence to support the intervention.Research in this area is complicated by the fact that RCTs necessarily assess the combined impact of measurement of ICP with the clinical management decisions made in light of this data. Future studies will need to assess the added value of ICP data alongside other information from the multimodal monitoring typically performed in intensive care unit settings. Additionally, even within traumatically acquired brain injury (TBI), there is great heterogeneity in mechanisms, distribution, location and magnitude of injury, and studies within more homogeneous subgroups are likely to be more informative.

It's easier to relearn gross motor skills than learn them for the first time after injury: Empirical evidence informing the age at injury debate.

The effect of age at injury on outcomes after brain injury has long been debated. Many have argued that the greater plasticity of the immature brain aids in its recovery from trauma, but others (notably Donald Hebb) have argued that early injury can impair the future ability of the brain to acquire new capabilities. This is difficult to assess empirically due to the presence of many age-dependent confounders. We performed Item Response Theory (IRT) analyses of two datasets of Gross Motor Function Measure (GMFM) observations, one in children with cerebral palsy (CP) and one in children with acquired brain injury (ABI) sustained at later ages. We used IRT to derive independent estimates of test item difficulty in the two populations. Additionally, where comparison between GMFM items and items in the Denver II Developmental Screening Test battery was possible we used the latter to obtain the ages at which these abilities are acquired in typically developing children. Item difficulty estimates for the two populations are highly correlated (adjusted r2=0.89, p<0.0005), but demonstrate significant bias with harder items (typically acquired at later ages) being more readily achieved by children with ABI compared to CP. These results support the Hebbian perspective that (when considering gross motor function) it is easier to maintain or recover previously established functions than to learn them for the first time in an injured brain. This argues for a more cautious outcome prognosis in injury at very young ages.

Early mobilisation and rehabilitation in the PICU: a UK survey.

OBJECTIVE: To understand the context and professional perspectives of delivering early rehabilitation and mobilisation (ERM) within UK paediatric intensive care units (PICUs). DESIGN: A web-based survey administered from May 2019 to August 2019. SETTING: UK PICUs. PARTICIPANTS: A total of 124 staff from 26 PICUs participated, including 22 (18%) doctors, 34 (27%) nurses, 28 (23%) physiotherapists, 19 (15%) occupational therapists and 21 (17%) were other professionals. RESULTS: Key components of participants' definitions of ERM included tailored, multidisciplinary rehabilitation packages focused on promoting recovery. Multidisciplinary involvement in initiating ERM was commonly reported. Over half of respondents favoured delivering ERM after achieving physiological stability (n=69, 56%). All age groups were considered for ERM by relevant health professionals. However, responses differed concerning the timing of initiation. Interventions considered for ERM were more likely to be delivered to patients when PICU length of stay exceeded 28 days and among patients with acquired brain injury or severe developmental delay. The most commonly identified barriers were physiological instability (81%), limited staffing (79%), sedation requirement (73%), insufficient resources and equipment (69%), lack of recognition of patient readiness (67%), patient suitability (63%), inadequate training (61%) and inadequate funding (60%). Respondents ranked reduction in PICU length of stay (74%) and improvement in psychological outcomes (73%) as the most important benefits of ERM. CONCLUSION: ERM is gaining familiarity and endorsement in UK PICUs, but significant barriers to implementation due to limited resources and variation in content and delivery of ERM persist. A standardised protocol that sets out defined ERM interventions, along with implementation support to tackle modifiable barriers, is required to ensure the delivery of high-quality ERM.

Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder.

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members. In these 57 patients we identified 49 different mutations, including six multiple exon deletions, six known mutations and 37 novel mutations (13 missense, five nonsense, 13 frame shift, four splice site and two translation initiation mutations). Clinical data were retrospectively collected from referring physicians by means of a questionnaire. Three different phenotypes were recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2 years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental retardation and movement disorder, without epilepsy (15%); and (iii) one adult case of glucose transporter-1 deficiency syndrome with minimal symptoms. Recognizing glucose transporter-1 deficiency syndrome is important, since a ketogenic diet was effective in most of the patients with epilepsy (86%) and also reduced movement disorders in 48% of the patients with a classical phenotype and 71% of the patients with a non-classical phenotype. The average delay in diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years (range 1 month-16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range 0.9-2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was below 0.50 in all but one patient (range 0.19-0.52). Cerebrospinal fluid lactate was low to normal in all patients. Our relatively large series of 57 patients with glucose transporter-1 deficiency syndrome allowed us to identify correlations between genotype, phenotype and biochemical data. Type of mutation was related to the severity of mental retardation and the presence of complex movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type of mutation and phenotype. In conclusion, a substantial number of the patients with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study demonstrates that a lumbar puncture provides the diagnostic clue to glucose transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic delay to allow early start of the ketogenic diet.

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.

Routine intracranial pressure monitoring in acute coma.

BACKGROUND: Studies in traumatic encephalopathy first led to the insight that the damage seen was not just due to direct consequences of the primary injury. A significant, and potentially preventable, contribution to the overall morbidity arose from secondary hypoxic-ischaemic damage. Brain swelling accompanied by raised intracranial pressure (ICP) resulted in inadequate cerebral perfusion with well-oxygenated blood. Detection of raised ICP could be useful in alerting clinicians to the need to improve cerebral perfusion, with consequent reductions in brain injury. OBJECTIVES: To determine whether routine ICP monitoring in all acute cases of severe coma reduces the risk of all-cause mortality or severe disability at final follow-up. SEARCH STRATEGY: We searched the Cochrane Injuries Group's Specialised Register (searched 7 April 2009), CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE 1950 to March week 4 2009, EMBASE 1980 to week 14 March 2009, CINAHL 1982 to March 2009, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to March 2009, Conference Proceedings Citation Index- Science (CPCI-S) 1990 to March 2009, PubMed (searched 7 April 2009, limit; added in last 6 months). The searches were last updated in April 2009. SELECTION CRITERIA: All randomised controlled studies of real-time ICP monitoring by invasive or semi-invasive means in acute coma (traumatic or non-traumatic aetiology) versus no ICP monitoring (that is, clinical assessment of ICP). DATA COLLECTION AND ANALYSIS: Primary outcome measures were all-cause mortality and severe disability at the end of the follow-up period. MAIN RESULTS: No studies meeting the selection criteria have been identified to date. AUTHORS' CONCLUSIONS: There are no data from randomised controlled trials that can clarify the role of ICP monitoring in acute coma.

Long-term outcomes of functional neurological disorder in children.

OBJECTIVES: To establish the incidence and long-term outcomes (up to 21 years) of children presenting to a University hospital paediatric neurology service with symptoms due to functional neurological disorder (FND) with particular reference to occurrence of FND or similar symptoms in adulthood. METHODS: Retrospective chart review to determine characteristics of the original paediatric FND presentation plus record-linkage with providers of Child and Adolescent Mental Health Services. Chart review of adult medical records for documentation of functional symptoms in adulthood. RESULTS: 124 individuals (56% female) met entry criteria. The most common presentations were seizures (18%), sensory loss (18%) and motor symptoms (16%). Frequency gradually increased with age of onset with an incidence in paediatric neurological services of 6 per 100 000 children under 16. In up to 21 years' follow-up (median 8.3 years), 114/124 attained their 16th birthdays by the study census date and were thus eligible for inclusion in an analysis of symptom persistence/recurrence in adulthood. 26/114 (23%) showed evidence of FND in adulthood of sufficient significance to be recorded in medical records. CONCLUSION: Paediatric FND is commoner than previous estimates. Even in this selected population of children reaching specialist paediatric neurology services, a high long-term remission rate is observed.

Prediction of raised intracranial pressure complicating severe traumatic brain injury in children: implications for trial design.

OBJECTIVES: To describe current patterns of management of raised intracranial pressure (ICP) in traumatic brain injury relevant to clinician buy-in to possible randomized controlled trials of treatments of raised ICP. To examine the feasibility of early identification of children at sufficient risk of developing raised ICP to permit a uniform approach between centers to the initiation of ICP monitoring. This would permit quantification of ICP elevation and enrollment as appropriate to randomized controlled trials of raised ICP interventions. DESIGN: Logistic regression modeling of death before pediatric intensive care unit discharge and decision tree and logistic regression of development of raised ICP through analysis of a prospectively collected, standardized, national data set. SETTING: Pediatric intensive care units in the United Kingdom and Eire. PATIENTS: Patients were 501 children <16 yrs of age primarily admitted to intensive care unit for management of traumatic brain injury in the United Kingdom and Eire between February 2001 and August 2003. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The data analyzed included demographic, acute physiologic, and cranial imaging variables. Death was associated with both raised ICP and the nonmeasurement of ICP. In a subset of 199 patients, an empirically derived decision rule predicted the development of raised ICP at any point during ICU admission with sensitivity of 73% and specificity of 74% (positive predictive value 82% and negative predictive value 63%). Logistic regression modeling performed comparably. The decision rule also predicted raised ICP in 20% of children not undergoing ICP monitoring. CONCLUSIONS: Simple models based on early clinical data may predict the development of raised ICP sufficiently well to encourage a consistent approach between centers to initiation of ICP monitoring. We estimate studies designed to detect reductions in ICU mortality will require >320 children per arm, although this figure may be higher if more conservative assumptions are made.

Requirements for and current provision of rehabilitation services for children after severe acquired brain injury in the UK: a population-based study.

OBJECTIVES: Survival with brain injury is an outcome of severe illness that may be becoming more common. Provision for children in this situation has received little attention. We sought to estimate rates of severe paediatric acquired brain injury (ABI) requiring rehabilitation and to describe current provision of services for these children in the UK. METHODS: This study conducted an analysis of Hospital Episode Statistics data between April 2003 and March 2012, supplemented by a UK provider survey completed in 2015. A probable severe ABI requiring rehabilitation (PSABIR) event was inferred from the co-occurrence of a medical condition likely to cause ABI (such as meningitis) and a prolonged inpatient stay (>=28 days). RESULTS: During the period studied, 4508 children aged 1-18 years in England had PSABIRs. Trauma was the most common cause (30%) followed by brain tumours (19%) and anoxia (18.3%). An excess in older males was attributable to trauma. We estimate the incidence of PSABIR to be at least 2.93 (95%CI 2.62 to 3.26) per 100 000 young people (1-18 years) pa. The provider survey confirmed marked geographic variability in the organisation of services in the UK. CONCLUSIONS: There are at least 350 PSABIR events in children in the UK annually, a health problem of similar magnitude to that of cerebral palsy. Service provision for this population varies widely around the UK, in contrast with the nationally coordinated approach to paediatric intensive care and major trauma provision.

Back to the future: rehabilitation of children after brain injury.

A mistaken optimism persists that outcomes for childhood acquired brain injury (ABI) are in general superior to those for similar injuries in adults, a misconception based on naive concepts of greater 'plasticity' in the immature brain. The challenges of rehabilitation after ABI, of bringing children 'back' to face the 'future' of completing childhood development with an injured brain, are reviewed in the context of the science of brain recovery from injury. Unrealistic expectations of recovery may cause subsequent events to be perceived as academic or employment 'failure'. The challenges of supporting children and families after ABI are reviewed.

Modelling early recovery patterns after paediatric traumatic brain injury.

OBJECTIVE: To describe the range of early recovery patterns seen in children admitted for inpatient rehabilitation after traumatic brain injury and to build simple predictive models of expected recovery. PATIENTS: 103 consecutive paediatric admissions to a neurological rehabilitation facility after closed head injury. METHODS: Children's recoveries were defined by repeated scores on the WeeFIM (a validated paediatric measure of functional independence) assembled into recovery trajectories. Non-linear mixed effects modelling was used to define 'typical' recoveries and to identify useful simple predictor variables. RESULTS: WeeFIM recovery curves showed a characteristic sigmoidal form with an initial slow phase followed by a mid-phase of fastest improvement and a late plateau. Final WeeFIM scores ranged from 18 to 125 (median 105, IQR 87-117). The time taken to reach 50% final WeeFIM score ranged from 5 to 145 days (median 27, IQR 17-46). Both final WeeFIM and time to reach 50% final WeeFIM correlated with time to follow commands (TFC), defined as the post-injury day on which a child was first observed to follow two simple commands in a 24 h period. CONCLUSIONS: Simple models predicting outcome trajectory can be built incorporating early rate-of recovery indices (such as TFC) as proxies of injury severity. Such models allow informed discussion with families of likely rates of progress and the CI on these estimates. Models of this nature also potentially allow identification of children making better- or worse-than expected recoveries.

A novel GLRA1 mutation in a recessive hyperekplexia pedigree.

We report the identification of a novel Y228C mutation within the M1 trans-membrane domain of the GLRA1 subunit of the glycine receptor responsible for a severe recessive hyperekplexia phenotype in a Kurdish pedigree.