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Abstract

Pediatric disorders of consciousness (PedDOC) encompass conditions that may occur following very severe traumatic or other forms of acquired brain injury sustained during childhood. As in adults, PedDOC is described as a disturbance of awareness and/or responsiveness. PedDOC is a complex condition that requires specialized care, infrastructures, and technologies. PedDOC poses many challenges to healthcare providers and caregivers during recovery and throughout development. In this commentary, we intend to highlight some considerations, controversies, and caveats on the diagnosis, prognosis and treatment of PedDOC.

Keywords

Pediatrics disorders of consciousness minimally conscious state vegetative state coma brain injury

1 Introduction

Disorders of consciousness (DoC), include several behaviorally defined states, including coma, vegetative state (VS), and minimally conscious state (MCS), with further subdivision in minus (MCS-) and plus (MCS+). These states have been originally defined in both adults and children, although most of the literature has focused on adults (Edlow et al., 2021), and only recently has PedDOC received significant attention in the literature (Molteni et al., 2023). In fact, DoC states have been described in children older than 5 years of age. In very young children reports of the behavioral features of DoC are limited (Alvarez et al., 2019), and for children under the age of 1 year or those with motor impairment there is a general lack of evidence that these definitions can be successfully applied.

More generally, research in the diagnosis, prognosis, and treatment of PedDOC provides overall low evidence, being largely made up of case studies and series. Despite the potential life-long impact of PedDOC on patients and their families, there is a lack of high-quality research in the field. Most research involves single center work examining small, heterogeneous clinical samples and including children from a wide age range who sustained very severe brain injuries from varying etiologies. Few studies examined long-term outcomes after PedDOC. Overall, the lack of high-quality studies limits the availability of conclusive evidence to inform diagnosis, prognosis, and clinical management. Ethical constraints, the heterogeneity of PedDOC etiologies, rarity of PedDOC, uneven or skewed age distributions, and different comorbidities all challenge the hypotheses verification through high-powered samples. Multicenter studies and data or model sharing are needed to overcome these limitations in the future (Irzan et al., 2022).

1.1 Foundational and observational gaps

The development of consciousness in typical children is not yet well understood, especially in very young ages. Despite advances in neuroscience, the precise mechanisms underlying the structuring of consciousness in early infancy remain unclear (Lagercrantz & Changeux, 2009). One reason for this is the difficulty in objectively measuring and quantifying consciousness in young infants, who are unable to communicate their subjective experiences. It has been suggested that consciousness may be a continuum that emerges gradually over the course of development, while others propose that it is assembled through discrete entities that arise at specific points in time (Padilla & Lagercrantz, 2020). To date, no definitive consensus has been reached regarding the development of consciousness in very young typical children. Further research is needed to shed light on this process and its implications for PedDOC.

Operationally, the determination of when in development it is appropriate to apply the definition of PedDOC remains a matter of debate, with no consensus on the specific etiologies that can result in PedDOC and on the earliest age when the diagnosis can be applied. Behavioral features of PedDOC can be observed in children with a range of etiologies, including neurological conditions present at birth or soon after. While PedDOC is typically used to describe disordered consciousness after very severe brain injury in individuals who previously demonstrated consciousness, some consider the term PedDOC to also encompass disordered consciousness arising from etiologies present at birth or soon after (i.e., prior to the development of consciousness), including congenital, neurodevelopmental, or neurodegenerative conditions in childhood (Ashwal & Cranford, 2002). In fact, when applying behavioral features of PedDOC more broadly, prevalence of DoC in childhood is more common following other conditions than severe traumatic and other acquired brain injuries (Strauss et al., 2000).

Moreover, the natural history of PedDOC is not well understood and likely varies depending on the child’s age and the nature of the brain injury or neurological condition. In adults, DoC of 28 days or longer is considered prolonged and there are studies that inform natural history of recovery in adults with prolonged DoC due to traumatic or anoxic brain injury (Giacino et al., 2018). In contrast, few studies have specifically described children in prolonged DoC of 28 days or longer and many pediatric studies do not report length of DoC or examine outcomes separately across varying etiologies or age ranges (Molteni et al., 2023). Given the heterogeneity in etiologies and age at onset, and the rarity of PedDOC in general, it is particularly challenging to study the natural history of PedDOC and to understand the impact of both age and etiology on outcome.

While natural history in PedDOC is not well understood, there is evidence to suggest differences in outcomes in those with traumatic versus anoxic brain injury. Similar to adults, children with anoxic etiology who remain in VS for more than 90 days are likely to remain in chronic DoC (Molteni et al., 2023). Additionally, current evidence on late recovery outcomes (Emergence from MCS occurring > 1year) in children with DoC remains limited to around 10 cases, all aged 13 years or older, in most cases having traumatic etiology, and none with significant anoxic brain injury (Molteni et al., 2023). It is unclear, however, whether lack of reports in children younger than 13 years is due to a gap in the scientific literature, originates from the lack of suitable assessment tools for younger children, results from suboptimal care of very young cases, or reflects the differences in the etiology of DoC in infancy compared to adolescence. Alternatively, it might be a clinically meaningful finding, indicating that very young children with DoC have lower likelihood of recovery, compared to adolescents. For instance, pediatric cardiac arrest survivors, which may have significant anoxic brain injury, are more likely to be younger than 5 years of age at the time of arrest (Slomine et al., 2016). Further observational research is needed to better understand the long-term outcomes and recovery potential in very young children with DoC.

The lack of characterization of the natural history of prolonged DoC in children with various etiologies has critical implications for the design of clinical trials, and particularly for those investigating early treatments in the acute phase of PedDOC. Following traumatic and anoxic brain injury, early treatments aimed at preventing secondary damage have the potential to significantly impact the long-term outcomes and prognosis of children with very severe injury. For example, targeted temperature management is the standard of care in children who are comatose upon resuscitation after pediatric cardiac arrest (Wyckoff et al., 2022). There is also evidence to suggest that hypothermia is more beneficial than normothermia in this group of children (Harhay et al., 2023). In contrast, hypothermia does not improve neurological outcome and may increase mortality after pediatric traumatic brain injury (Hutchison et al., 2008). Caution is advised when developing interventional studies for children with DoC arising from varying etiologies, as efficacy of treatments is likely to be influenced by many factors, including the age of child, etiology of injury or condition, and timing of intervention administration. Efficacy might also be subject to different interpretations, depending on duration of PedDOC diagnosis. Therefore, agreement is essential to determine when to use the term PedDOC and prolonged PedDOC in clinical trials, as this will affect patient selection, treatment protocols, and outcome assessments.

In PedDOC, several characteristics and associated clinical features are poorly studied and have been rarely reported. For this reason, our knowledge is fragmentary. Examples of important characteristics that have not been well described in the literature include age at onset, age at evaluation, time from onset to evaluation, state of DoC at evaluation, and standardized outcomes assessment. Examples of associated clinical features that are not consistently reported include need of ventilation and tracheotomy, bowel and bladder management, insurgence of frequent infections, paroxysmal sympathetic hyperactivity, need and incidence of cranioplasty [e.g., (Leonardi et al., 2013)]. However, there is increasing evidence that management of medical complications related to some of these features, such as successful resolution of infections and of the cranioplasty sequelae, is associated to recovery from PedDOC, including cases of late improvement (Molteni et al., 2023). For this reason, it is important to systematically record and analyze all the core elements of DoC, including negative findings.

1.2 Uses and challenges in behavioral assessment

Behavioral assessment is a critical aspect of the management of PedDOC, as it informs about the patient’s level of consciousness, responsiveness, and cognitive abilities. Additionally, state of PedDoC early after injury (e.g., at admission to rehabilitation) is associated with later outcome (e.g., Rodgin et al., 2021). However, the use of scales and tools for behavioral assessment in children with DoC presents several challenges.

Typically, adults and children with DoCs manifest fluctuations of their arousal level (Molteni et al., 2023). Ideally, patients should be assessed when their arousal state is optimal. For this reason, arousal maximization is essential pre-requisite to the neurobehavioral assessment. Strategies for arousal maximization include environmental manipulation, sensory stimulation, and the use of medications when appropriate. Salience of stimuli is fundamental in children (Machado et al., 2007; Nicholas et al., 2014). This is obtained though personalization of the assessment material. Stimuli personalization involves the use of individualized and tailored stimuli to promote engagement and interaction with the environment. In children, the use of familiar cues becomes essential. These include the preferred lullabies, music, toys, and cartoons/characters (Magee, 2018). Affective prompting, such as the parents’ voice, touch, laugh, etc. is also essential element for promoting arousal (Nicholas et al., 2014). However, several challenges remain. Children with DoC often present with impaired sensory perception and/or processing, which can make it difficult to determine the appropriate level of stimulation (Dovgialo et al., 2019; Duszyk et al., 2019). Additionally, these children may also have difficulty communicating their preferences, making it challenging to tailor stimuli to their individual needs. Therefore, specialized methodology including caregiver interviews and systematic trials of stimuli can be considered to identify highly idiosyncratic stimuli that can be incorporated to optimize arousal in children with DoC (Amari et al., 2017). Additionally, the management of PedDOC requires a multidisciplinary team of healthcare professionals with specialized training and expertise (Lahey et al., 2017).

One other challenge is the lack of validation of some scales and tools in children, especially in very young children. Many behavioral assessment scales and tools have been developed and validated in adult populations or adolescents and may not be appropriate for use in younger children, especially those aged younger than 4 years. The Coma Recovery Scale Revised (CRS-R) has been applied to children aged 5 years and older (Frigerio et al., 2022). Other scales used in children are the Coma/ Near Coma Scale, Level of Cognitive Functioning Assessment Scale (Molteni et al., 2020), Western Neurosensory Stimulation Profile and Post-Acute Level of Consciousness scale (Eilander et al., 2009).

Furthermore, the restricted range of developmental skills in very young children limit the utility of these standardized instruments, which were designed to measure skills that have not yet emerged (e.g., command following, intelligible verbalizations), for assessing DoC. A pediatric version of the CRS-R, the Coma Recovery Scale for Pediatrics (CRS-P) has been developed and shown to detect signs consistent with emergence from a minimally conscious state in typically developing children as young as 12 months of age (Slomine et al., 2019). Preliminary data from a sample of children admitted to an inpatient rehabilitation setting with DoC suggests this measure can be used to detect states of PedDOC in children under 5 years of age [(Suskauer, 2023), unpublished]. While promising, further validation of tools, especially for the youngest children, is needed.

The lack of standardized assessment tools and scales that are validated for use in very young children with DoC (those < 5 years of age) has important implications for clinical practice. Clinicians may be forced to rely on subjective measures, or on evaluations lacking sufficient sensitivity or specificity for appropriately assessing the patient’s level of consciousness and/or responsiveness. This may ultimately lead to imprecise diagnoses and delayed treatment plans, thus also affecting patient outcomes. In research, this lack of validated tools might hinder research efforts and limit the identification of the effects of various interventions in very young children. Assessment of PedDOC is even more challenging for children who had neurodevelopmental delays and/or known longstanding neurodevelopmental disabilities.

Also, while signs of awareness of self and/or the environment observed during behavioral assessment can help confirm the presence of consciousness, in individuals with DoC, potential confounders may impact the sensitivity of behavioral evaluation (e.g., severe motor impairment). Therefore, it cannot be concluded that consciousness is not present if signs of awareness are absent during behavioral examination. In adults, there is support for the use of neuroimaging and neurophysiological measures to detect covert consciousness (CC), defined as the presence of residual brain activity and subjective experience in the absence of behavioural responses (Kondziella et al., 2020). Emerging research suggests that neuroimaging and neurophysiological measures can also be used in children with DoC to detect signs of CC (Boerwinkle et al., 2023; Kim, O’Sullivan, et al., 2022).

1.3 Uses and challenges in neurophysiology

The use of electroencephalography (EEG) in children is common for diagnosing complications of PedDOC, such as epilepsy (Patrick et al., 2006; Snyman et al., 2010). In intensive care units (ICUs), EEG is frequently used to detect seizures in children with DoC who might otherwise not demonstrate behavioral signs of epileptic activity. Its use for the investigation of the level of consciousness is promising (Kim, O’Sullivan, et al., 2022; Machado et al., 2014) but still limited. The immature development of children’s brains at the time of injury, with age-dependent changes in the patterns of EEG activity, makes it challenging for the scientific community to develop normative data and diagnostic criteria that are both specific to age, and to levels of consciousness.

The integration of Event Related Potentials (ERPs) into the assessment of PedDOC is also beneficial for decreasing diagnostic uncertainty. Short-latency somatosensory evoked potentials (SSEPs) examination is valuable in comatose children, when there is need to prognosticate between favorable and unfavorable outcome (Carrai et al., 2010). Indeed, normal SSEPs generally correlate with favorable outcomes, and abnormalities or the absence of SSEPs upholds unfavorable prognoses (Wohlrab et al., 2001). Nevertheless, exceptions to these associations have been reported, and dichotomous (i.e., favorable vs. unfavorable) prognostication is insufficient to many therapeutic decisions in PedDOC. Furthermore, the occasionally discordant findings between short- and long-term assessments point to the intricate interplay of brain plasticity and compensatory mechanisms in children, suggesting that prognosis should not rely on early SSEP measurements. Visual evoked potentials (VEPs) exhibit diminished prognostic power compared to SSEPs in PedDOC. However, higher P300 amplitudes are observed in children who emerged from minimally conscious states (MCS), compared with those who did not emerge. In sum, while ERPs hold value in the assessment of pediatric DoC, their integration requires careful consideration of the broader neurophysiological context and a cautious approach in clinical decision-making (Ismail et al., 2022).

Recently, event related potentials (ERPs) features associated to sensory processing and attention orientation have been detected in three unresponsive children, conjointly with components attributed to attempted command following, and independently of residual motor function (Kim, Watson, et al., 2022). Such features have thus been proposed as potential markers of dissociation between motor and cognitive abilities. Albeit intriguing, replication studies are needed before introducing these markers in the clinical practice, also in view of their age- and lesion- dependent nature.

Polysomnography (PSG) includes EEG, electromyography, and other physiological signals to assess the circadian rhythm and the quality and stages of sleep. PSG employment in post-acute settings has been reported by independent groups (Avantaggiato et al., 2015; Mouthon et al., 2016), and a rating scale is available for PedDOC (Avantaggiato et al., 2015). Conversely, use of PSG is not (yet) reported in ICUs, where it could be most useful to continuously monitor the restructuring of sleep/wake patterns. The primary barriers to the use of PSG in ICUs are the interference with medical maneuvers, the need for high-expertise due to intrinsic complexity of data interpretation, and the high time and resource requirements of evaluation, caused by the vastity of the generated data. Recent advancements in artificial intelligence have made it possible to automate the analysis of complex medical data, including PSG (Perslev et al., 2021). With the application of deep learning algorithms, PSG data can be analyzed automatically and in real-time, which could reduce the need for expert interpretation and increase appeal of PSG use for anticipating behavioral changes in consciousness in critically ill children.

Last, reports on combined use of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) with EEG in adults with DoC are accumulating. These studies will help clarify the potential of the techniques in PedDOC and will drive the technical adjustments preliminary to the transfer to the pediatric field.

1.4 Uses and challenges in neuroimaging

Imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) are used for identifying the underlying etiology and extent of brain injury which provides essential information about diagnosis and prognosis of PedDOC (Vitello et al., 2022). While CT and MRI are largely used in the acute phase, to monitor the ongoing brain damage over the first hours and days after the primary injury, MRI is increasingly used in the post-acute and chronic phases of PedDOC to inform treatment, thanks to the non-ionizing nature of the technique. When studying brain damage over months and years, however, all pediatric studies share one main challenge.

The growth of white and grey matter in the brain keep to nonlinear curves, with rapid changes in the first few years of life, followed by slower trajectories in later childhood and adolescence (Aubert-Broche et al., 2013; Liang et al., 2023). The nonlinearity of growth patterns can make it challenging to accurately interpret imaging findings in children with DoC, and especially the ongoing progressive atrophic phenomena, which should be evaluated as negative volume drifts from the expected growth curves, and not as purely (negative) differential computations in between subsequent MRI scans.

In group-analysis for research, one additional challenge is the need for age-based brain atlases. CT and MRI images must be studied and interpreted in the context of age-specific norms, as the anatomy and development of the brain change rapidly during childhood. The use of adult-based atlases can lead to misinterpretation of imaging findings in children with DoC, as normal developmental changes can be mistaken for pathological changes. Therefore, age-based atlases should always be used to accurately interpret imaging findings in children with DoC (Ou et al., 2017; Zöllei et al., 2020).

Functional MRI (fMRI) has been regarded as one of the most promising techniques for the investigation of brain functions. It has been proposed as first-line approach to identify residual cognitive activity in behaviorally unresponsive patients with DoC, and a tool to attempt communication restoration. However, the use of fMRI in PedDOC has been sporadic (Nicholas et al., 2014), and limited to anecdotical findings (Boerwinkle et al., 2019) from single cases. Patients with DoC may require sedation to reduce motion artifacts in MRI environment, which can affect the reliability of the fMRI results. In children, interpreting fMRI data in the context of consciousness disorders can be even more complex, as the reliability of intra-subject resting state networks is not well-established in infants, and there is lack of normative on how blood-oxygen-level dependent (BOLD) activity, a measure obtained through fMRI measurement, relates to the level of consciousness. These factors, together, might have discouraged research in fMRI for PedDOC.

Also, resting-state fMRI (rs-fMRI) is a valuable tool for identifying CC. While rs-fMRI may not be suitable for detecting CC in preverbal children who might still be unable to semantically access the instructions or requests, this technique can uncover signs of hidden awareness and responsiveness in older children presenting with specific language and/or motor impairments (Ismail et al., 2022). However, there should be awareness that developmental differences are associated with varying levels of axonal myelination, differentially affecting the acquired BOLD signal (Munson et al., 2006).

Positron emission tomography (PET) also allows for the assessment of brain metabolism in PedDOC (Larsen et al., 1993; Snyman et al., 2010). Despite its potential clinical utility, the use of PET is limited in children, due to its reliance on radioactive tracers, which present safety concerns. Additionally, there is a general lack of normative data for children, which challenges the interpretation of PET results. Furthermore, identifying the best region of interest (ROI) for referencing quantitative analysis is challenging in PedDOC, as generalized depression of metabolic activity is commonly observed over all the brain, including the cerebellum. Potentially, PET usability will increase through the development of safer and more efficient radiotracers, together with the availability of richer normative data, and along with the agreement on standardized protocols for reference ROI selection and data analysis.

Due to the clinical complexity of PedDOC, the ideal neuroimaging technique would certainly be ecologic and applicable at the bedside. Along this line, attempts have been made to study the functional brain activity using near-infrared spectroscopy (NIRS), a non-invasive technique probing changes in oxygenated and deoxygenated hemoglobin in the blood vessels. However, its use is limited by its inability to access the deep brain structures (e.g., thalami and basal ganglia) in individuals other than newborns, and by its high rate of false positives (Molteni et al., 2013).

Lastly, multimodal neuroimaging has been identified as the opportunity to advance knowledge on the complex neurophysiopathology of DoC. While the vulnerability of children with DoC is an obstacle to multiple neuroimaging assessments and complex imaging procedures, the integration of CT/MRI, CT/PET, EEG/MRI and MRI/PET technologies brings feasibility to the multimodal approach, and unprecedented completeness to the data available to PedDOC research, thanks to the synchronicity of recordings from diverse physiological phenomena. These multimodal techniques have the potential to be important tools for clinical care in the future.

1.5 Uses and challenges in pharmacology

Pharmaceuticals are increasingly used for treating DoC in children (Irzan et al., 2022; Molteni et al., 2023). In the acute stage after the development of DoC, it is difficult to determine if recovery of consciousness is due to the impact of medication or natural recovery. In addition, polypharmacy, the concurrent administration of a medication for PedDOC with other treatments to address symptoms such as spasticity, pain, and agitation, or complications such as epilepsy and infections, is very often necessary. Thus, assessing efficacy of specific medications to promote recovery in PedDOC, especially early after injury, is challenging. Dopaminergic agents, such as Amantadine, have the most evidence supporting their use as neurostimulants in children (McLaughlin et al., 2021; McMahon et al., 2009). Zolpidem, which has GABAergic effects, has been found efficacious in one out of 15 adults with DoC (Bomalaski et al., 2017); in children, reported cases are still insufficient to determine effectiveness (Snyman et al., 2010).

Moreover, there are gaps in our understanding of the optimal dose and duration of treatment for potentially efficacious agents. For instance, in a recent paper exploring the prescribing patterns of Amantadine across inpatient brain injury rehabilitation units, there was high dosage variability, which was not completely explained by factors such as child weight, age, and the state of DoC when the treatment is provided (McLaughlin et al., 2021). Dosage adjustments may be required to achieve therapeutic effects while avoiding adverse symptoms, such as sedation or respiratory depression. Additionally, children with DoC may have comorbidities, such as epilepsy or renal impairment, which can further complicate drug dosing. Thus, more research into dosing of pharmaceuticals for PedDOC is warranted. Another challenge is the duration of overall pharmacological treatment. Children with DoC often require long-term pharmacological management, which can be associated with the development of medication adverse effects, intolerance, or dependence.

The stage of DoC when the treatment is provided is also a critical factor in the use of medications in children. Early intervention with appropriate pharmacological management may prevent the development of secondary complications and improve long-term outcomes. However, the optimal timing of medication treatment for PedDOC in children remains unclear, and further research is needed to inform clinical decision-making. There is also evidence from a case report to suggest that even if stimulant medication is not helpful early after injury, it may be helpful months or years later (Pennington et al., 2011).

Lastly, although high-level evidence is generally lacking on PedDOC pharmacology, it is undeniable that the availability of early reports on the administration of Amantadine for PedDOC has encouraged the clinical community to further explore the efficacy of other dopaminergic medications such as methylphenidate or levodopa in children with DoC (Pennington et al., 2011; Yeh et al., n.d., 2019a).

1.6 Uses and challenges in interdisciplinary rehabilitation

Inpatient rehabilitation provided by a skilled interdisciplinary team is recommended for adults in prolonged DoC. In fact, in 2020, minimum competencies for rehabilitation programs for individuals with DoC were developed based on a modified Delphi voting process (Giacino et al., 2020). Unfortunately, treatment recommendations for PedDOC are limited and minimum competencies specific for PedDOC rehabilitation are non-existent. Therefore, healthcare providers working with children in DoC often extrapolate from the adult literature. An interdisciplinary model of inpatient rehabilitation has been described for children with DoC (Yeh et al., 2019b). Interdisciplinary goals of care, based on adult literature and highlighted in this model, include assessment of arousal, responsiveness and function, optimization of night-time sleep, optimization of daytime arousal, optimization of function, and caregiver training. More research is needed to better understand the effective components of interdisciplinary rehabilitation for PedDOC and how rehabilitation may need to be adapted based on the age of the patients. Additionally, more research is required to better characterize the rehabilitation needs of children with DoC over time and identify those children who may benefit from a boost of more intensive rehabilitation later in development.

1.7 Uses and challenges in assistive technology

In the vast majority of children with DoC, the condition entails communication and motor deficits. Hence, assistive technology (AT) is often an important element in the management of PedDOC, as it can enhance patients’ expression, interaction with the environment, and improvement of the quality of life (Stasolla et al., 2022). Young children with neurological impairments who would benefit from use of AT have unique physical or cognitive characteristics that make it difficult to use standard AT devices. As a result, AT devices may need to be adapted or miniaturized to meet the specific needs of each child. Tasks gamification requires adaptation to the child’s accessible sensory pathways, age, and cognitive abilities. Robotic devices such as treadmills and exoskeletons need to be adapted in size depending on the child’s anthropometry, and in the delivery of generally lower, yet more precise forces and torques (Irzan et al., 2022). All these accommodations need to be considered when utilizing AT for children emerging from DoC. This requires the availability of staff with specialized training and expertise with children with neurological injuries/illness, who have also understanding of the emergence from DoC.

Employment of brain-computer interfaces (BCIs) has not yet been reported in PedDOC. However, several studies exist which explore their feasibility in children and adolescents (Kim, O’Sullivan, et al., 2022; Kinney-Lang et al., 2020; Zhang et al., 2019). The first challenge in pediatrics is the definition of the minimal consciousness ability that is both developmentally appropriate and preserved after injury to enable successful BCI interaction. Secondly, responses and behaviors must be sufficiently reliable to support their own classification by the interface. Thirdly, pediatric BCI paradigms should be customized, age-appropriate, and engaging to cater to children’s shorter attention spans and sensitivity to fatigue. Lastly, the use of BCI in children requires careful consideration of its potential impact on cognitive functions and developmental processes, especially in cases where invasive implantation will be considered (Nicholas D. Schiff et al., 2014).

2 Ethical issues unique to pediatric DoC

There are numerous profound ethical issues unique to PedDOC. A complete review of these issues is beyond the scope of this commentary. We will just highlight a few of the major ethical issues in PedDOC. In adults with DoC, uncertainty surrounding diagnosis and prognosis complicates decision making around establishing of care. Uncertainty in diagnosing DoC and predicting outcomes is even greater for children (Giacino et al., 2018; Molteni et al., 2023), especially infants (Brecht & Wilkinson, 2015). Therefore, it is challenging to provide families with accurate information early after injury or illness to make informed choices about goals of care. To minimize harm to the child and family, healthcare providers utilize available, evidence-based diagnostic and prognostic tools to provide families with most accurate and timely information regarding diagnosis and prognosis, while also acknowledging uncertainty (Kirschen & Walter, 2015). Additionally, when a poor prognosis is likely, some families prioritize lifesaving care regardless of outcome whereas others believe that limits of care or withdrawal of care should be considered. To respect parent autonomy, family values are used as the foundation for guiding care (Kirschen & Walter, 2015). Also, there are no accepted guidelines pertaining to treatment of PedDOC; hence justifying treatment based on strong evidence can be challenging. As a result, treatments for children with DoC may not be available or may not be reimbursed for all patients who would benefit from these treatments. To maximize benefits, minimize harm, and acccess equity in access in children with DoC, healthcare providers continue to advocate for evidence-based treatments and researchers continue to study the efficacy of potential treatments.

3 Conclusions and future directions

In conclusion, PedDOC is a complex condition with a unique set of considerations, controversies, and caveats that requires dedicated research effort. Our knowledge on the diagnosis, prognosis, and treatment of PedDOC is based on low-evidence studies, with the majority describing single cases or small series, and few illustrating small-sized clinical trials. Research reports need standardization, and systematic description of core elements of PedDOC. There is also need of statistically powered trials, and especially for the identification of the best treatment strategies and dosages (or intensities). Further research is also needed to assess the applicability of all the definitions of the states of consciousness, and to better validate standardized neurobehavioral assessment measures for children with DoC, especially those in the earliest ages when motor and cognitive skills are rapidly developing (<5 years of age). Imaging techniques such as MRI and CT are essential for the diagnosis and management of PedDOC. However, when applying neuroimaging to children, methods have to be chosen that are robust to variations in contrasts and to nonlinearity of growth curves, and age-appropriate brain atlases have to be carefully selected or assembled for group-analyses. Greater consensus and guidelines are also needed for treatment of PedDOC, including pharmacological intervention, interdisciplinary rehabilitation, and assistive technology. Despite these obstacles, efforts are being made to increase the amount and quality of research in the field. Collaborative research networks are being established to facilitate multicenter clinical studies and data pooling. Additionally, advances in technology and imaging techniques may provide new avenues for understanding and treating DoC in children. Efforts to address these criticalities will contribute to personalize the approach to the disorder and will pursue the ultimate goal of improving the care and outcomes of children with DoC.

Conflict of interest

None to report.

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Nicholas Schiff,

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Pediatric disorders of consciousness: Considerations,controversies,and caveats

Abstract

Keywords

1 Introduction

1.1 Foundational and observational gaps

1.2 Uses and challenges in behavioral assessment

1.3 Uses and challenges in neurophysiology

1.4 Uses and challenges in neuroimaging

1.5 Uses and challenges in pharmacology

1.6 Uses and challenges in interdisciplinary rehabilitation

1.7 Uses and challenges in assistive technology

2 Ethical issues unique to pediatric DoC

3 Conclusions and future directions

Conflict of interest

References