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Lost among the trees? The autonomic nervous system and paediatrics
  1. Corinne A Rees
  1. School of Social and Community Medicine, University of Bristol, Bristol, UK
  1. Correspondence to Dr Corinne A Rees, Westgate House, Southmead Hospital, Westbury on Trym, Bristol BS10 5NB, UK; drcarees{at}


The autonomic nervous system (ANS) has been strikingly neglected in Western medicine. Despite its profound importance for regulation, adjustment and coordination of body systems, it lacks priority in training and practice and receives scant attention in numerous major textbooks. The ANS is integral to manifestations of illness, underlying familiar physical and psychological symptoms. When ANS activity is itself dysfunctional, usual indicators of acute illness may prove deceptive. Recognising the relevance of the ANS can involve seeing the familiar through fresh eyes, challenging assumptions in clinical assessment and in approaches to practice. Its importance extends from physical and psychological well-being to parenting and safeguarding, public services and the functioning of society. Exploration of its role in conditions ranging from neurological, gastrointestinal and connective tissue disorders, diabetes and chronic fatigue syndrome, to autism, behavioural and mental health difficulties may open therapeutic avenues. The ANS offers a mechanism for so-called functional illnesses and illustrates the importance of recognising that ‘stress’ takes many forms, physical, psychological and environmental, desirable and otherwise. Evidence of intrauterine and post-natal programming of ANS reactivity suggests that neonatal care and safeguarding practice may offer preventive opportunity, as may greater understanding of epigenetic change of ANS activity through, for example, accidental or psychological trauma or infection. The aim of this article is to accelerate recognition of the importance of the ANS throughout paediatrics, and of the potential physical and psychological cost of neglecting it.

  • General Paediatrics
  • Comm Child Health
  • Child Psychology
  • History Of Medicine
  • Paediatric Practice

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The ability to adapt in a timely manner, appropriate to circumstances, is essential to reliable daily function: the autonomic nervous system (ANS) is pivotal to doing so. Its roles are many and complex. It is relevant to physical and mental health and illness, development and behaviour, parenting and safeguarding. It offers a mechanism for psychosocial dimensions of paediatrics. It is the face of illness.

Childhood presents preventive possibilities through influencing the programming of adaptive responses, with potentially lifelong, even intergenerational implications, affecting numerous causes of premature death and debility.1 Childhood neural plasticity allows amelioration of dysfunctional initial programming and of consequences of maladaptive reprogramming caused by, for example, infection, psychological trauma or injury.

The extent of underrepresentation of the ANS in general paediatric clinical services and research is an anomaly of substantial public health importance. The mismatch with other areas of medicine presents particular challenges to progress. Filling the gap requires recognition, first, of the importance of doing so.

What does it do?

While the evolutionary and developmental origins of the ANS may be somewhere akin to the traditional image of an all-or-nothing mediator of ‘fight or flight’ and ‘rest and digest’, it in fact underpins highly sophisticated adaptive responses (box 1).

Box 1 Roles of the autonomic nervous system

Adjustment to the physical environment

  • Temperature: brown fat metabolism, vasodilation/vasoconstriction, piloerection, sweating

  • Light: circadian rhythm, melatonin/melanin secretion

  • Altitude: respiratory rate, heart rate, haemopoiesis

  • Gravity: postural adaptation—vasoconstriction, blood pressure adjustment

Adjustment to threat

  • Regulation of anxiety, fear, anger

  • Adjustment of concentration, sensory input (eg, pupil size), sensory sensitivity, pain perception

Management of threat

  • Fight, flight, freezing

  • Influencing of immunity and allergy involving cytokines, mast cells, lymphoid tissue

Use of resources

  • Facilitation of optimal use of resources by circadian rhythm, sleep and alertness

  • Control of movement to reach resources, appetite, thirst

  • Control of gastrointestinal motility, secretion, digestion

  • Control of metabolism; storage and release of energy, adipocyte proliferation, insulin, glucagon and leptin secretion, lipolysis, gluconeogenesis


  • Facilitation of individual and cooperative development of skills at times of low threat; focussing attention for study, planning, organisation

  • Mediation of motivation and reward


  • Coordination of multiorgan feedback with external stimulus to adapt function to circumstances

  • Mediation of multifaceted regulation via individual organs (eg, renal haemodynamics, rate of solute reabsorption)


  • Mediation of sexual attraction and function


  • Influencing of osteoblast/osteoclast activity, hepatic fibrogenesis, haemopoiesis

  • Influencing of inflammation and wound healing


  • Control of bladder and bowel function to suit circumstances


  • Balancing of vigilance to threat against focus on relationships; balances individual and group priorities

  • Allowing focus of attention for ‘reading’ relationships, emotional awareness and empathy, including parental attachment

  • Mediation of cooperation and competition, and communication of threat and emotion

  • Mediation of perception of time

The ANS is integral to adjustment to all to which adjustment is required, whether internal or external, environmental, physical or psychological, individual or interpersonal, or any combination of these. ‘Stressors’ may be welcome or otherwise, including light, sound, touch, heat and pain, gravity, danger and excitement, distress and pleasure, infection and injury among many. The ANS adjusts sensitivity to all modalities of sensory input and environmental conditions. It coordinates physiological, psychological and behavioural adaptation to these, and their detail, in an integrated hierarchy of centrally generated multisystem patterns, integrating the demands of extraneous stressors with intrinsic homeostasis.2 Despite having multiorgan manifestations, traditional teaching is that the ANS has little role in motor control: common experience suggests otherwise, however, as does an evolutionary role in fight and flight.

By colouring verbal and non-verbal communication, ANS function influences the quality of relationships and thus the functioning of society. It is involved in emotional regulation, and in communication of, for example, fear, anxiety and excitement.3 ,4 Parents’ regulatory capacity prominently affects that of their children and influences the quality of the attachment on which they depend, this relationship forming a template for others.5

The ANS anticipates the extent of need to adapt. It generates alertness and sensory sensitivity when danger warrants it, allowing concentration, intellectual learning and its application, reproduction or somnolence when it does not, optimising available resources through circadian rhythm, and cooperation through time perception.6 It adjusts fitness and modulates pain sensitivity according to circumstances.7 It modifies the extent to which vigilance to the environment overrides, or not, the value and possibility of sensitive attunement to others.

Sympathetic and parasympathetic functions are not merely antagonistic. Some organs are innervated by one, some by both; unexplained paradoxes remain apparent. Differential function of receptors and neurotransmitters, and cotransmitters within individual neurones, allow subtle attunement of function to need. The presumed principal sympathetic and parasympathetic neurotransmitters, noradrenaline and acetylcholine are only part of the story. For example, their precursors, including dopamine and gamma-aminobutyric acid (GABA), serve independently and synergistically; serotonin, glutamate and nitrous oxide modulate gastrointestinal function; glutamate is prominent in central ANS control.8 There are aspects hovering on the edge of practically applicable understanding—including the relevance of magnesium to the ANS9 and of the ANS to immunity,10 mast cell function,11 vasopressin and oxytocin12 and glucose metabolism.13

It follows that ANS dysfunction has potentially profound implications, touching all specialties.

Set for action? Development, programming and reprogramming

The linked ANS and hypothalamus-pituitary-adrenal (HPA) axis are thought to be programmed in utero and the early post-natal months to equip children for the environment in which they are born.14 ,15 However, at this level the system lacks specificity. Pathways whose evolutionary role ensured vigilance to, say, predators, are those which anticipate domestic aggression, or are perhaps programmed through antenatal stress or unpredictable pain during neonatal intensive care—a matter of degree.

Programming does not merely reflect ambient stress per se, but also how effectively it is controlled. With little capacity for independent regulation, babies depend on carers to do so. Programming is therefore influenced by the quality of attachment, reflecting parents’ physical and emotional ‘availability’, on a spectrum affected by, for example, post-natal depression, substance abuse or domestic violence. Parental stress regulation is necessary to achieve it for children.5 Secure early attachment equips the relationship-dependent prefrontal cortex to regulate automatic responses16: dysregulation is a common sustaining consequence of dysfunctional foundations.17

Regardless of foundations, trauma-induced or infection-induced epigenetic change offers a route to ‘baseline shifts’, as exemplified by post-traumatic stress disorder syndrome (PTSD).18 Adaptive ANS function may fail to ‘switch off’ when circumstances change, becoming counterproductive. For example, visceral function adaptive to infection or injury becomes unhelpful if it becomes fixed, generating chronic pain, inflammation and illness. Similarly, high reactivity beneficial to children living with aggression becomes problematic in safe circumstances—in school or in adoptive homes, for example. Like war veterans, children may go through life ‘set for action’ when little is needed, ‘fight or flight’ eroding self-esteem by engendering cause for discipline, peer relationship problems and sometimes parental rejection—pouring stress into a system set to respond dysfunctionally to it.19 ,20


Exploring the relevance of the ANS in general paediatric practice involves noticing the detail of what is described and observed, how symptoms and signs cluster and what alleviates and exacerbates them. Recognition is helped by noting parallels with conditions seen in other specialties in paediatrics and adult medicine and with features of identified autonomic disorders (table 1, box 2). Comparisons show common themes, familiar also in everyday experience of ‘stress’, positive and negative, physical (eg, infection, exertion), environmental (eg, heat, altitude, hazard), psychological (eg, excitement, distress) or interpersonal (eg, anger or approval), and conveyed in idiom. Adult patients’ descriptions can shed light on children's experiences (table 2).

Table 1

Comparison of symptoms in conditions to which the ANS is prominently contributory

Table 2

Comparison of common experience and idiom with adult and paediatric patients’ descriptions

The task involves shedding preconceptions and building a jigsaw of pieces of varying clarity, adjusting this as experience accumulates. It means taking fresh perspectives on the familiar. For example, the sensory hypersensitivity, altered pain perception, emotional dysregulation and anxiety symptoms of autism make sense as manifestations of sympathetic activity inadequately modified by parasympathetic function22 via the relationship-driven prefrontal cortex—a pattern also common in once-abused children.23 Symptomatic parallels occur in migraine, cyclical vomiting, chronic fatigue syndrome (CFS/ME), PTSD and Ehlers-Danlos syndrome (EDS). In all, undampened sympathetic activity may generate physical and psychological manifestations of stress with ‘normal’ stressors—‘normal’ symptoms but incongruous with circumstances.

Experience in the few centres of excellence, particularly of rare familial autonomic disorders, needs to be optimally used.24 ,25 Checklists initially developed in relation to these should have increasing broad application, as should therapeutic insight.26 Indicators common in general paediatric contexts should prompt closer scrutiny (table 3).

Table 3

Some possible pointers to ANS dysfunction in general paediatrics: history

Box 2 Looking for patterns: case outlines in general paediatrics

Cerebral palsy

Spastic quadriplegia following perinatal hypoxia. By age 9: temperature dysregulation, alternating tachycardia and bradycardia, vomiting, retching, abdominal pain, fluid retention/pleural effusions. ‘Sympathetic storms’ precipitated by pain, infection, psychological stress (tachycardia— eg, 180/min, hypertension, skin flushing/blotching, irritability, anxiety, tremor, tachypnoea, hypoxia, sudden onset oedema, increase in secretions). ‘Hibernation’ states (bradycardia, apnoea, reduced temperature, prolonged unrousable sleep).

Traumatic brain injury

Multiple injuries in road traffic accident: intensive care. Rehabilitation complicated by tachycardia and hypertension which, with recovery, became intermittent, exacerbated by intercurrent infections, then ceased.

Neonatal intensive care

Neonatal intensive care for infection. Close family relationships. Parental anxiety due to neonatal separation. Infancy—irritability, sleep disturbance, vomiting. Childhood—‘functional vomiting’. From adolescence—mild obsessive compulsive disorder, anxiety, migraine, IBS.

Intrauterine drug exposure

Intrauterine stress and drug exposure. Eighteen months of dysfunctional parenting before foster care: insecure attachment. Despite secure adoption: hyperactivity, inattention, sleep disturbance. Emotional dysregulation/temper with pounding heart and pallor provoked by excitement, frustration, discipline. Repeatedly excluded from lessons.

Intrauterine stress and mild hypermobility

Intrauterine violence. Foster care on neonatal discharge, then adoption. Sudden switches into rage through excitement or provocation, with tachycardia, hyperventilation, increased temperature, hypersensitivity to touch (soft touch experienced as painful), ‘remoteness’. Vivid dreams; profuse nocturnal sweating. Hands icy cold or very hot; skin marking readily (red marks, wheals and bruises). Hypermobile thumbs.

Intergenerational autonomic nervous system programming

Mother: Childhood abuse; IBS, fibromyalgia, temper dysregulation, poor concentration, parenting difficulty.

Child: Intrauterine stress. Domestic violence in infancy. Insecure attachment, temper dysregulation, ‘ADHD’.

Intrauterine exposure to alcohol, crack cocaine and stress

Exposure to crack cocaine, alcohol and stress in utero. Foster care from 5 days. Disliked wrapping in infancy. Age 19 months: short concentration span, hyperactive, little eye contact. Sensory hypersensitivity: pulls off clothes, resists stroking and cuddles; agitation, tachycardia and high pitched scream in supermarkets etc. Emotional dysregulation: becomes out of control (hyperactive, screeching) if excited in play.

Foetal alcohol syndrome

Heavy maternal drinking in pregnancy: happily adopted. Difficulty in handling stressors (eg, birthdays, Christmas, criticism, noisy environments, crowds): pupils dilate, feels fear, heart races, temper, facial colour drains, hands and feet icy, seems ‘detached’ from her surroundings (not noticing cold, falling, lacking usual care etc), fatigue, urgency, wetting, anorexia, reflux. Insomnia. Chronic constipation. Helped by massage, stroking, yoga.

Early emotional abuse; atypical autistic features

Severe emotional abuse in infancy. Following adoption—hyperactive, poor concentration, emotional dysregulation, anxiety, high need for control, lack of speech unless alone or in relaxed play, sensory hypersensitivity. Use of trampoline helpful before tasks requiring concentration.

Ehlers-Danlos syndrome (hypermobility type)

1. Well until age 13. Close family relationships, active, socially integrated. Age 13: infectious mononucleosis, then continuing malaise. Age 15: Increasing difficulty in walking, postural tremor, transient inability to control her hands. Seizure–like painful muscle spasm, preceded by ‘internal tremor’ after going up stairs. Intermittent difficulty swallowing, vomiting, abdominal distension. Markedly unstable blood pressure; orthostatic tachycardia. Good recovery with midodrine, clonidine and hydrotherapy. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

2. Well until age 8. Close family relationships, active, socially integrated. Age 8: mycoplasma infection, then continuing malaise, low grade pyrexia, headache, pallor; premature satiety, succussion splash, post-prandial distension, abdominal pain, constipation. After puberty: progressive orthostatic intolerance; positive Romberg sign; loss of voluntary movement, speech and swallowing; sensory hypersensitivity; generalised pain; icy peripheries, blotchy skin, dermatographia; sleep disturbance. Tachycardias (200+), syncope; seizure-like painful muscle spasm, myoclonus, tremor, intermittent hyperreflexia, profuse sweating. Age 21: Diagnosis EDS (hypermobility type), orthostatic tachycardia, pan-gastrointestinal dysmotility with marked paucity of ganglia, gastroparesis, megacolon, atonic bladder, chronic bladder wall infection.

Severe CFS/ME

Well until age 14. Close family relationships. Happy, active, socially integrated. Talented ballet dancer. The family joked about her ‘bendiness’. Age 14: BCG vaccination, then numerous infections including infectious mononucleosis. Syncope and palpitations. Rapidly progressing illness: multiple syncope with seizure-like muscle spasm. Became bedbound with loss of speech, voluntary movement and swallowing. Vomiting; tube-fed. Hypersensitivity to light and sound. Drenching sweats, hot flushes. Generalised pain. Diagnosed as ‘severe CFS/ME’.

Post-traumatic stress disorder syndrome—adult

Following military and civilian trauma: tachycardia, sweating, tingling, muscle spasm, nausea, ‘disconnection’ precipitated by environments of high sensory stimulus (eg, supermarkets) or psychological stress. Insomnia, irritability, fatigue, mood swings. Helped by breathing exercises and physical exertion.

The ANS underlies gastrointestinal disorders without local structural abnormality (eg, irritable bowel syndrome, gastroparesis, constipation, reflux, colic, cyclical vomiting, recurrent abdominal pain): it is, equally, contributory where abnormality is visible (eg, ulcerative colitis, Crohn's, Hirshprung's, megacolon, pyloric stenosis).27–33

The relationship of asthma to physical and psychological stressors suggests autonomic prominence. The ANS is integral to obesity through its interrelationship with leptins,34 to complications of diabetes35 and to migraine.36 It contributes to symptoms of cerebral palsy,37 Rett syndrome,38 Guillain-Barre syndrome39 and multiple sclerosis (MS) and to consequences of intrauterine drug and alcohol exposure40 and substance abuse.

The ANS influences immunity and autoimmunity and is integral to connective tissue disorders including rheumatoid arthritis, Sjogren's and systemic lupus erythematosus (SLE).41 EDS (notably ‘hypermobility type’—‘type 3’) is an under-recognised source of generalised ANS dysfunction, sometimes producing complex multisystem disability and one of many causes of postural tachycardia (PoTS) (figures 14).42 ,43 ANS immaturity contributes to apnoea of prematurity44 and to sudden infant death syndrome. Its dysfunction underlies sleep-related apnoea; its role in circadian rhythm and arousal underlies sleep disorder. ANS influence is prominent in poorly understood areas—CFS/ME, for example.45 It underlies many conditions currently described as ‘functional’.29

Figure 1

Ehlers-Danlos syndrome hypermobility type: Hypermobility.

Figure 2

Ehlers-Danlos syndrome hypermobility type: Acrocyanosis.

Figure 3

Ehlers-Danlos syndrome hypermobility type: Unattributed bruising.

Figure 4

Ehlers-Danlos hypermobility type: Raynaud's phenomenon.

The ANS is equally pertinent to problems of behaviour, concentration, emotional regulation and temper, and to symptoms of, or mimicking, mental health problems such as anxiety disorder, panic attacks, dissociation, PTSD, bipolar disorder, personality disorder and eating disorders.46–53 Anxiety, dissociative symptoms and panic would be unsurprising manifestations of autonomic dysfunction, fluctuating alongside others, without need, necessarily, to consider them ‘comorbidities’ or assume complex psychopathology, any more than is so of infection-related ‘delirium’.

ANS dysfunction complicates assessment of intercurrent illness. It mimics infection by generating pyrexia, pallor, malaise and lymphadenopathy, adding ambiguity by modulating and sometimes perpetuating pain, generalised or localised, as in chronic regional pain syndrome (CRPS). It accentuates medication side effects. The ubiquitous role of the ANS in illness illustrates reason to capitalise on, not reject, placebo effects.

One might predict greater risk for children programmed for hazard by, for example, antenatal stress, neonatal intensive care, post-natal depression, or abuse, on a spectrum of severity. Others’ histories might identify infection or trauma as flicking a (probably epigenetic) switch.

Preventing harm

ANS function matters at many levels in safeguarding children, including from iatrogenic harm.

Unhelpful programming of regulatory systems is among the most troublesome sustaining consequences of early abuse and neglect, often refractory even to successful adoption, affecting integration at home and school,14 ,15 so is an important consideration in safeguarding children. Protection requires consideration of the dependence of children's regulatory capacity on that of their parents and on adequate mutual attachment.16 Parents’ dysregulation, often reflecting their own early parenting, often managed through substance abuse and often manifest in temper problems, readily produces vicious circles of escalating parenting difficulty, dysregulated children's behaviour fuelling stress.20

The relevance of the ANS to ease of bruising, skin marking, healing rates and bone density, and to gastrointestinal control, immunity, growth and behaviour, make this an important consideration in assessment.10 ,54–56

ANS dysfunction carries risk of iatrogenic harm: physical and psychological.57 Harm may result from a lack of suitable—or suitably informed—services. If evidence determines, rather than guides services, those with unexplored conditions may lack provision. Disadvantage may result from over-specialisation, whereby each sees distorting fragments of the overall picture, allowing misassumption to flourish. Because the ANS straddles specialties, patients may fit nowhere. Since young people depend on others’ feedback in building their identity and self-perception, misattribution matters. Unrecognised knowledge gaps carry psychological risk. If, for example, ‘medically unexplained’ is irrationally equated with ‘medically inexplicable’, blame may be sensed.

Since the ANS integrates mind and body, ANS dysfunction may exaggerate the association. A little stress, of any modality, may go far. ‘Psychological’ symptoms may or may not accurately represent psychological concerns. Stress experienced as trivial and non-aversive may nevertheless generate symptoms—‘as though the body feels anxious’—potentially confusing for the child, family and professionals.

ANS disorder is ‘functional’: it produces malfunction of end-organs which have the potential to function normally. ‘Functional’ is, however, a loosely applied, variably understood term, often seen by default as synonymous with ‘psychological’, this merging hazardously with ‘volitional’ or ‘behavioural’ if undefined and afforded no mechanism. Without a mechanism other routes to the same end-point are overlooked. ‘Stress’ is readily equated with ‘negative psychological stress’ and psychopathology potentially erroneously implicated. ‘Functional’ may imply physical insignificance, inviting disbelief and judgement: a retrievably non-functioning computer is not necessarily a trivial problem. ‘Symptoms without known physical cause’ suggests that there is none, 'Symptoms real to the patient’ that they would not be to others. Language matters.

Therapeutic considerations

There is much to learn. Children's care meanwhile means working sometimes from first principles, learning from patients and from disciplines in adult medicine and paediatrics which see analogous problems, and extrapolating experience from the few international specialist centres of rare genetic ANS disorders and neurovascular medicine. There may be lessons from ‘complementary’ therapies, music, sports medicine, deep-sea diver and astronaut rehabilitation, meditation and yoga practitioners.58–60

Paediatrics may offer opportunity to optimise the baseline of stress responses, by reducing ambient stress and by facilitating parental attunement through which its effects are regulated—for example in neonatology and in supporting vulnerable parents. Neural plasticity provides justification for encouraging mollification of stress responses upregulated by, for example, early exposure to violence. The starting point is parental stress regulation: infants depend on this for theirs, and all children are influenced by it. Similarly important is protection of the attachment which mediates the link. The aim is to teach stress regulation through play, discussion and role model, implementing it through environmental calm, minimising anxiety, maximising calming through others and encouraging self-regulation (box 3).61

Box 3 Regulating children's stress

Parental stress regulation

Recharging time; adequate support networks

Support of attachment

Encouragement of attunement

1:1 time

Calming through the environment

Limited sensory stimulus (eg, television, computers, supermarkets, fluorescent lights, crowds)

Calming lighting, music etc

Reduction of anxiety

Routine, explanation, consistent expectations and consequences; reassurance after discipline

Maximise success (eg, 1-to-1 time)

Calming through relationships

Talking re feelings

Shared calm closeness; massage; stroking

Stress release

Exercise: for example, punch bag, trampoline, running

Singing, percussion, dance


‘Calm corner’ with positive associations

Music, relaxation, meditation, yoga

‘Portable’ calming strategies (eg, stress balls; breathing/blowing games)

Established maladaptive ANS function is, in significant part, a problem in relation to prevalent demands—eased by adjusting them. For example, noisy schools or supermarkets may precipitate dysregulation for once-abused children, equipped for danger. Adults can choose environments which suit their regulatory capacity—children cannot. The aim is, however, adjustment to normality, not avoidance. Rewriting the ‘pacing’ principle from ‘a finite pot of energy’ to ‘a finite pot of tolerable stress of all modalities’ allows applicability to diverse routes to ANS dysfunction. A baseline of manageable stress, achieved by modifying the environment, may gradually be stretched towards tolerance of a less constrained one, capitalising on neural plasticity. For example, adoptive parents of previously abused children are encouraged to ‘attune but not too much’, easing towards normal opportunity.61 Problematic stressors may be rendered manageable by, for example, an otherwise calm environment, music, meditation, humour, diversion, choice and control. Minimising ‘unhelpful’ stressors reserves capacity for valuable ones, the distinction depending on individual priorities. Relaxation or exercise before demanding activities may increase capacity for them. Consequences of undampened sympathetic activity are modified by elevating vagal tone: relatively inexpensive approaches such as massage, yoga and music may be beneficial in, for example, diabetes, cerebral palsy, disordered attachment, prematurity, pain control, recovery from brain injury and the management of connective tissue and autoimmune disorder and autism.58–61

The impact on quality of life of diffuse ANS disorder may be profound, not least because of its unpredictability. There may be associated or secondary anxiety or depression, and predisposition to PTSD. While ANS dysfunction may distort the apparent significance of psychological stressors, managing them nevertheless matters. Low-key, pragmatic psychological support may be unavailable in overstretched CAMHS services; insightful specialist nurses can play an invaluable part. Factors underlying dysfunctional programming or subsequent epigenetic change may, or may not, be long-since resolved, and may, for some, bring associated difficulties. For example, those whose ANS responses were programmed dysfunctionally through abuse or neglect may also struggle with, for example, identity, self-esteem and relinquishing attention, influencing their responses to illness, sometimes warranting specific support.

Management of PoTS depends on its cause, severity and consequences. When attributable to deconditioning alone, reconditioning alone can correct it. For others, simple measures to protect circulatory volume, such as elastic stockings and high fluid and salt intake may adequately protect cerebral circulation, control secondary sympathetic overdrive and prevent deconditioning. Evaluated pharmacological options include midodrine, fludrocortisone, clonidine and octreotide among others.43 For some, complex multisystem disorder demands coordinated, multiprofessional care, facilities for which are however few.42 ,43 Because multiple factors interrelate, promptly addressing remediable stressors such as infections, pain, dehydration or psychological stress may prevent vicious circles whereby consequences of unregulated stress, recumbency and deconditioning perpetuate it. Adjusting remediable elements may allow to others correct.

Iatrogenic stress requires consideration. Potentially effective treatment presented without trust may flounder through generating stress. ‘Driven’ physiotherapy, or treatment offered in a busy, noisy environment, may fail when approaches encouraging regulation succeed. Time to listen, explain, tailor care individually and build trust may be wise economy. Pharmacological options remain, generally, off-licence for ANS dysfunction, despite evidence of efficacy. They usually facilitate rehabilitation rather than providing the sole solution.


The extent to which consideration of the ANS has lagged behind other aspects of medicine creates a troublesome anachronism, mismatched with and excluded by professional practice which has developed largely without reference to it. Remedying this presents considerable challenges for a profession struggling to meet existing demands, when specialisation diffuses responsibility. It is a task, effectively, of rewinding and rebuilding. The starting point is to notice the detail of what patients describe, clusters of symptoms, common themes and physical signs, scrutinising anomalies. It means adjusting the focus between individual characteristics, research and professional preconceptions, while recognising how historical neglect colours professional attitudes and patients’ experiences. Once patterns are recognised, the role of the ANS becomes noticeable through the many guises generated by its wider connections, allowing applicability of common principles to be explored. Evidence alone cannot complete the picture. As with any jigsaw, ambiguous pieces are also needed, to be rearranged as their significance emerges.

Recognition of the relevance throughout paediatrics of the ANS means shedding labels, accompanying assumptions and perhaps prejudice, describing from first principles rather than naming, and disregarding preconceptions about the origins of symptoms. It means being ready to see the familiar through different lenses, mindful that ‘fact’ often conceals uncertainty and that similar symptoms may be conceptualised in differing ways. The role of the ANS in hitherto poorly explained illness warrants particular scrutiny. Its historical neglect means that most diagnoses evolved without acknowledging its relevance. ANS dysfunction may generate numerous potentially misleading diagnoses if the origins of symptoms are overlooked or each is seen in isolation.

The ANS story provokes thought about implications of current approaches to medical practice and about the cost to patients of unrecognised knowledge gaps.62 It illustrates ironically irrational by-products of ‘scientific’ medicine. Diagnoses become seemingly circumscribed entities with variable justification—an illusion when clinical signs are poorly recognised, without biological markers, and when knowledge is, necessarily, incomplete. Unrecognised heterogeneity makes uncritical evidence-based practice hazardous. Assumption flourishes when diagnosis-related evidence determines, rather than guides patients’ care. Diagnosis-based care-pathways mean that patients need to fit services, not the converse; evidence-based rationing means no service if evidence has yet to accrue. Professional approaches warrant the objective scrutiny afforded to clinical practice.

Risk through label-based assumption is compounded by specialisation, whereby the expectation of understanding others’ fields has receded. Professional mind-body separation may cause particular difficulty. ‘Psychological’, undefined, can become a mere gap-filling default. If a mind-body association is misconstrued as unusual it invites stigma. Children may pay heavily for failure to distinguish ‘stress-related’ (multimodal, positive and negative, physical and psychological) from ‘psychological’, and, worse, ‘psychological’ from ‘behavioural’ or ‘volitional’. Table 1 illustrates why ANS-related conditions are commonly misattributed to ‘anxiety’. Anxiety-like manifestations, like physical symptoms, are a problem if they are a problem and may or may not require advice in their own right. Misassumption may come from disregard of mechanism, whereby diverse routes to final common paths of ANS-related symptoms are overlooked—hazardous if, for example, parental neglect is one such route, and infection, injury and genetics are others (table 4).

Table 4

Scope for confusion: comparison of symptoms and diagnostic labels associated with a primarily genetic and a primarily psychosocial basis for ANS dysfunction

Relevance of ANS dysfunction to CFS/ME would do much to explain the mutual mistrust which hinders progress: its role warrants comprehensive assessment. For the poorly studied subgroup who are profoundly ill, the possibility of specific treatment makes elucidation of the role of the ANS an urgent priority. Many are untreated, feeling professional abandonment and sensing blame.63 Symptomatic parallels between severe EDS/PoTS, ‘severe CFS/ME’ and ‘pervasive refusal syndrome’64 demonstrate the risk of assuming there to be ‘refusal’ and the importance of ANS evaluation (table 5). National Institute of Health and Care Excellence (NICE) guidelines for CFS/ME65 do not encourage identification of EDS/PoTS, for which considerable evidential treatment is available, although those affected may meet its diagnostic criteria.

Table 5

Illustration of the importance of ANS evaluation in ‘severe CFS/ME’ and ‘pervasive refusal syndrome’

The interrelationship of children's and parents’ regulatory capacity, the relevance to both of environmental stressors, and the sustaining importance of regulatory foundations acquired through early attachment, indicate one mechanism for psychosocial dimensions of paediatrics, risk factors for future physical and mental health, and scope for prevention. A relationship between dysfunctional parenting and ANS dysfunction suggests routes to refining child protection practice and to reducing costly delay when, without demonstrable injury, professionals struggle to present a persuasive case for intervention.

Psychological safety warrants the vigilance currently afforded to physical safety—responsibility to ‘get it right’ being equally great. Removing mystique from psychology would help to ensure that psychological consideration is fully integral to paediatrics. Working from first principles can, for example, allow consideration of the quality of parental attachment and its implications to be routine.5 Developing identity, moulded by others’ feedback, makes psychologically appropriate care particularly important during childhood and adolescence: without the cognition or maturity to challenge it, professional misperception may be internalised, to the detriment of self-esteem. ‘Psychological’ like ‘physical’ should be rejected as a generic term, each needing definition, supportive indicators and plausibility. ‘Medically unexplained’ should become ‘medically unexplained so far’, and ‘functional’ afforded a mechanism. Protection of those within poorly understood medical territory warrants particular attention in service organisation and training, acknowledging that knowledge gaps exist, and are hazardous.

Adequate provision for the ANS sometimes merely means broadening the field of vision of established specialties, actively protecting generalism within them. However, for major multisystem disorder, established specialties may fall short. Commissioning presupposes recognition of what needs to be commissioned and why—a problem for conditions lost between specialties and diagnoses. Economy makes evidence necessary for funding—a problem for ‘new’ areas and for multifaceted conditions which awkwardly fit an evidential mould. Demonstration of need is difficult without an established service. The importance of the ANS should make cost-benefit considerations persuasive—an argument vulnerable, however, to devolved budgets: a baseline of no service ironically skews the equation.

How would a paediatric autonomic service look? There would be much in common in structure and content with pain teams—multidisciplinary and specialised while extending to the general, inside or outside hospital. Specialist nurses, equipped for outreach work, constitute a sound investment.

One may reflect that characteristics of care suited to the ubiquitous importance of the ANS in medicine are those eroded by an efficiency-driven, evidence-determined culture—aspects which our less ‘scientific’ predecessors no doubt saw as priorities—such as puzzlement, resolved by detailed listening, observation and examination, the ‘how’ as much as the ‘what’, and the therapeutic importance of trusted doctor–patient relationships developed through continuity. Have some babies perhaps slipped out with the bathwater?


Remedy of historical neglect of the ANS offers fresh perspectives on familiar paediatric problems, with implications for prevention, management and research. For those with severe generalised ANS dysfunction it is an urgent responsibility.

The potential for physical and psychological harm through professional inattention to the ANS demonstrates limitations of current approaches to organisation and practice which need to be acknowledged to maximise their benefit safely. It indicates the importance of maintaining a focus on individual detail in applying evidence, of remembering the distorting effect of specialisation, and of active protection of those whose conditions fall within knowledge gaps or straddle specialties. It means learning from history.



  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Commissioned; externally peer reviewed.