The declarations of interest of all participants in the various meetings have been given to the HAS, analysed according to the evaluation grid in the "Guide for declarations of interest and managing conflicts of interest", and taken into account to avoid any conflicts of interest. The conflicts of interest management committee has affirmed that the declarations of the work group members are
compatible with their participation in this group.
The guide and the declarations of interest of the experts who participated in one or several work group meetings can be consulted on the HAS website: www.has-sante.fr.
3. Documentary research
The HAS documentation department conducted the documentary research using predominantly the Medline database for the period from 1990 to 2012. The research equations are detailed in the scientific rationale, which can be consulted on the HAS website: www.has-sante.fr.
4. Participants
4.1. HAS Project Leaders Dr Muriel DHENAIN, HAS, project leader.
Dr Philippe BLANCHARD, HAS, project leader.
Mrs Emmanuelle BLONDET, HAS, documentalist.
4.2. Steering committee
Pr Jean-François MATHÉ, PMR physician, Nantes - steering committee chair.
Dr Jean-Jacques DUMOND, psychiatrist, Limoges.
Maître Emeric GUILLERMOU, solicitor, family representative, chair of the UNAFTC.
Pr Jean-Michel MAZAUX, PMR physician, Bordeaux.
Mr Michel ONILLON, establishment manager.
Pr Pascale PRADAT-DIEHL, PMR physician, Paris.
4.3. Work group
Pr Jacques LUAUTÉ, PMR physician, Lyon - work group chair.
Dr Angélique STÉFAN, PMR physician, Nantes, project leader.
Dr David PLANTIER, PMR physician, Giens, project leader.
Dr Laurent WIART, PMR physician, Bordeaux, project leader.
Dr Julia HAMONET, PMR physician, Limoges, project leader.
Mrs Annabelle ARNOULD, psychologist, Garches.
Mrs Suzanne AUBERT, family representative, UNAFTC.
Dr Jean-Marie BEIS, PMR physician, Nancy.
Mr Laurent BLAIS, Director, Maison Douglas, Mercœur.
Mrs Marie-Christine CAZALS, UNAFTC.
Dr Jean-Marc DESTAILLATS, psychiatrist, Bordeaux.
Dr Eric DURAND, PMR physician, Saint Maurice Hospital, Paris.
Dr Patrick FAYOL, psychiatrist, Limoges.
Dr Christine FIEYRE, MDPH physician, Paris.
Mr Luc JAGOT, psychologist, Nantes.
Dr Christophe LERMUZEAUX, psychiatrist, Institut Marcel Riviere, La Verrière.
Mr Jean-Michel LUCAS, PE teacher, Maison Douglas, Mercoeur.
Dr Dominique MALAUZAT, psychiatrist, pharmacologist, Limoges.
Mrs Nelly MONTROBERT, social worker, Aveize.
Maître Jacques Antoine PREZIOSI, solicitor, Marseille Mrs Antoinette PROUTEAU, psychologist, Bordeaux.
Pr Isabelle RICHARD, PMR physician, Angers.
Dr Laurence TELL, PMR physician, Lyon.
4.4. Reading group
Pr Philippe ALLAIN, Psychologist, Angers Dr Laurent ATLANI, PMR physician, Marseille Pr Philippe AZOUVI, PMR physician, Garches Dr Eleonore BAYEN, PMR physician, Paris Mr Christian BELIO, ergotherapist, Bordeaux Maître Richard BOMETON, magistrate, Limoges Mrs Céline BONNYAUD, physiotherapist, Garches Maître Marc CECCALDI, solicitor, Marseille
Mrs Renée CHAIGNON, social worker, Nantes Dr Emmanuel CHEVRILLON, PMR physician, Paris
Mr Dominique CHOPINAUD, healthcare executive, Limoges Mrs Christine CROISIAUX, psychologist, EBIS chair, Brussels Dr Xavier DEBELLEIX, PMR physician, Bordeaux
Mrs Brigitte DHERBEY, patient's family, UNAFTC
Mr Philippe HINGRAY, MAAF insurance, Niort Dr Corinne JOCKIC, PMR physician, Caen
Mrs Françoise JOYEUX, psychologist, Aunay sur Odon Dr Françoise LALOUA, PMR physician, Grenoble Pr Didier LE GALL, psychology, Angers
Mrs Jacqueline MADINIER, patient's family, UNAFTC Mrs Anne-Cécile MARQUET, IDE executive, Nancy Pr Michèle MONTREUIL, psychologist, Paris
Dr Hélène OPPENHEIM-GLUCKMAN, psychiatrist and psychoanalyst, Paris and Institut Marcel Rivière (La Verrière) Mrs Annie PERUSSEL, establishment manager, Nantes
Dr Bruno POLLEZ, PMR physician, Lille
Mr Stéphane RAFFARD, psychologist, Montpellier Dr André-Jean REMY, hepatologist – prison, Perpignan Dr Marc ROUSSEAU, PMR physician, Lille
Mrs Véronique ROUSSENAC, Psychologist, Kerpape Dr Virginie SAOUT, PMR physician, Angers
Pr Jean-Luc TRUELLE, neurologist, Garches Pr Yves ZERBIB, GP, Lyon
We would also like to thank Mrs Jacqueline MADINIER for proofreading the final version of the document.
5. Grading of recommendations
Each article selected was analysed according to the principles of critical literature reading using reading grids, thus providing a level of scientific proof for each one. According to the level of proof of the studies on which the recommendations are based, the grade varies from A to C in accordance with the HAS scale ("Literature analysis guide and grading of recommendations" January 2000, downloadable from the HAS website: www.has-sante.fr).
When no studies are available, recommendations are based on the agreement of the work group experts, after consulting the reading group. The absence of grading does not mean that the
recommendations are not pertinent and useful, but must encourage the implementation of additional studies.
Level of scientific proof in the literature
(therapeutic studies) Grade of Recommendation Level 1
High-power randomized comparative studies Meta-analysis of randomized comparative studies Decision analysis based on well-conducted studies
Established scientific proof A
Level 2
Low-power randomized comparative studies Well-conducted non-randomized comparative studies
Cohort studies
B
Scientific presumption Level 3
Case-control studies Level 4
Comparative studies with significant bias Retrospective studies
Case series
C
Low level of proof
Recommendations
1. Question 1: What are the different types of disruptive symptoms that can be treated 1.1. General information:
In the absence of consensus in the literature, we propose to divide behavioural disorders into 4 symptom sub-groups: (i) excessive behavioural disturbances; (ii) default behavioural disturbances;
(iii) behavioural disorders secondary to depression, anxiety and psychosis; (iv) attempted suicide and suicide.
Cognitive disorders and anosognosia are very common impairments that have a major impact on the long-term handicap of TBI sufferers. They are not specifically addressed, but are regularly mentioned due to the overlap with cognitive disorders, anosognosia, and behavioural disorders. Likewise, behavioural disorders secondary to sleep disorders and pain are voluntarily not addressed.
One objective is to provide a common nomenclature for professionals, patients and families based on well-accepted definitions. Another is to specify, according to the data in the literature, the incidence and factors for predicting these disruptions.
R1: All those involved must share the same definitions and nomenclature with regard to behavioural disorders (EC).
R2: Behavioural disorders can be classified as excessive behavioural disturbances, default behavioural disturbances, behavioural disorders secondary to depression, anxiety and psychosis, or attempted suicide and suicide (EC).
Observation: Behavioural disorders are twice as common following a traumatic brain injury compared with an orthopaedic trauma without TBI.
Observation: Behavioural disorders after TBI persist over time.
1.2. Excessive behavioural disturbances
This chapter groups several types of symptoms such as agitation, conflict, inappropriate wandering behaviour, disinhibition, irritability, impulsiveness, screaming, risk taking, bulimia, addiction, hypersexuality, exhibitionism, Klüver-Bucy* syndrome, hostility, aggressiveness, and verbal and physical violence. Each term satisfies more or less well-defined criteria.
Several of these symptoms are also observed in Alzheimer's and have the same characteristics (cf.
good practice guidelines: Alzheimer's and related diseases: treatment of disruptive behavioural disorders - HAS 2009). The generic term “agitated behaviour” can therefore include conflict,
aggressiveness, circadian rhythm disorders, wandering or inappropriate motor behaviour, screaming, and motor disinhibition.
Conflict corresponds to the patient's refusal to be treated, eat, wash, respect social rules, cooperate...
Anger can be defined as an emotional state consisting of feelings of varying intensity, from moderate irritation or annoyance to intense fury and rage. It emerges in response to provocative, abusive or frustrating situations. More generally, anger includes emotional, cognitive, behavioural, and
physiological reactions to certain situations. Three modes of expressing anger have been described:
anger-in, anger-out, and anger-control. Anger-in corresponds to anger expressed inwardly, anger-out corresponds to anger expressed outwardly aimed at people or surrounding objects, and anger control is an individual's capacity to control their anger.
In the Anglo-Saxon literature, anger is often grouped with hostility and aggression within the context
of the Anger-Hostility-Aggression (AHA) syndrome.
Inappropriate wandering behaviour is sometimes likened to agitation. It can involve verification, incessant pursuit, repetitive or excessive activity, wandering aimlessly or with an inappropriate goal, nocturnal wandering, roaming, with the need to be taken home...
Disinhibition corresponds to impulsive and inappropriate behaviour in relation to social or domestic standards at the time this behaviour is observed. Symptoms include absent-mindedness, emotional instability, inappropriate or overt behaviour: roaming, incongruous sexual attitude, indecent or invasive behaviour, self-aggression or aggression towards others. Abnormal sexual behaviour and hypersexuality can have a major impact on the family and society (cf. chapter on behaviour and forensic consequences). Disinhibition is characterised by poor control of impulsions (DSM*-IV-TR), and is a symptom of the frontal lobe syndrome. This behavioural disorder is more specifically linked to orbitofrontal cortex damage, which could modulate limbic system activity according to the
environmental context.
Some disruptions correspond to the alteration of normal functions. Therefore, impulsiveness could result in the alteration of one or several psychological factors such as imperiousness, premeditation, perseverance, and "sensation seeking". These disruptions can generally be addressed within the framework of dysexecutive syndrome behavioural disorders*.
The analysis of the literature highlights five sub-chapters: (i) agitation; (ii) aggressiveness; (iii) irritability; (iv) abuse and excessive consumption: high-risk, excessive, addictive behaviour; (v) behaviour resulting in forensic consequences, misdemeanour, crime.
R3: Agitation, conflict, inappropriate wandering behaviour, disinhibition, irritability, impulsiveness, screaming, risk taking, bulimia, addiction, hypersexuality, exhibitionism, Klüver-Bucy* syndrome, hostility, aggressiveness, verbal and physical violence... are excessive behavioural disorders (EC).
1.2.1. Agitation
1.2.1.1. Definition
Most authors consider that agitation occurs during a period of alteration of the state of awareness, which, in the case of a traumatic head injury, concerns in particular coming out of a coma. For some, it is an essential progressive stage following a traumatic brain injury. Indeed, observations have shown that cognitive improvement precedes a decrease in agitation, while interventions that decrease waking increase agitation.
Agitation is defined as excessive behaviour occurring during the alteration of the state of consciousness. This definition highlights the importance of "excessiveness" which is characterised by the degree above which the behaviour interferes with functional activities. No specific type of behaviour defines agitation, even if some behaviour such as psychomotor agitation may predominate.
* The DSM V is now available
According to some authors, post-traumatic agitation corresponds to a delirious state during a period of post-traumatic amnesia (PTA) characterised by excessive behaviour combining aggressiveness, akathisia, disinhibition, and/or emotional lability.
R4: Agitation following severe or moderate TBI occurs while awake (EC), and particularly during the period of PTA. Agitation includes one or more of the following signs:
impulsiveness, disrupted thought, disrupted perception, increased psychomotor activity, physical or verbal aggression, explosive anger, increased difficulty sustaining or adapting attention (EC).
R5: Factors contributing to post-traumatic agitation must be identified: pain, effect of psycho-stimulants (alcohol, drugs), benzodiazepine withdrawal, epilepsy, endocrine disorders, sleep disorders... (EC).
1.2.1.2. Incidence/prevalence
The average incidence of agitation in the population of traumatic brain injury sufferers is estimated at 46.3% (ranging from 35% to 70%). Post-traumatic agitation is generally brief (1 to 14 days), but can sometimes continue for longer or emerge later.
Observation: The average incidence of agitation in the population of traumatic brain injury sufferers is estimated at 46.3% (ranging from 35% to 70% depending on the studies).
1.2.1.3. Contributing or triggering factors
Observation: Environmental causes, sleep disorders, and pain have been as identified as factors that contribute to agitation.
Observation: Agitation is inversely proportional to participation in the rehabilitation programme.
1.2.2. Aggressiveness 1.2.2.1. Definition
The DSM-IV classification proposes the diagnosis of a personality change linked to a medical cause, with different sub-types according to the type of hostile behaviour (Theme III). The aggressive type is characterised by predominant aggressive behaviour directed at inanimate objects, self or others. The disinhibited type is characterised by disinhibition and sexual indiscretions; the patient can become aggressive if they are redirected or frustrated.
Aggressiveness also includes severe irritability, hostile, violent behaviour, assaults, and loss of self-control ("dysself-control"). A distinction is often made between goal-directed aggressiveness and hostile or explosive aggressiveness. The latter is observed more often after a traumatic brain injury.
Emotional lability can lead to verbal outbursts in reaction to minimal provocation, but with no substantial threat or violent behaviour.
In the Anglo-Saxon literature, several terms are used interchangeably: aggression, assaults, violence.
Other authors define aggressiveness as complex behaviour which includes one of the following components: (i) behaviour resulting in injury to an individual or damage to property; (ii) attitude, mood, gestures that people find threatening or intimidating; (iii) persistent behaviour which disrupts the rehabilitation activities and social reintegration.
R6: Aggressiveness includes verbal and physical aggressiveness against self, objects, and others, as well as severe irritability, violent, hostile behaviour, assaults, and loss of self-control (EC).
1.2.2.2. Incidence/prevalence
Observation: The incidence of aggressiveness in the population of traumatic brain injury sufferers reported in the different studies varies from 25 to 39%.
1.2.2.3. Contributing or triggering factors
The initial severity of the traumatic brain injury is correlated with a higher probability of hyperactivity, disinhibition and unhelpful thoughts (level 4). Prefrontal lesions, and in particular orbitofrontal lesions, are more common in aggressive patients. Increased anger and confusion are correlated with
executive control disorders (level 3).
Older age, a noisy environment, occurrence of epileptic fits in the previous 24 hours, and speech disorders (level 4) are also correlated with aggressive behaviour. Men are also more at risk.
Finally, serious depression and anxiety are the most common co-morbidities in aggressive TBI patients. The results of these studies are however influenced by the difficulty in interpreting whether the patient’s aggressive behaviour is recent or not, as the patient’s behaviour before the traumatic brain injury is rarely specified and difficult to assess.
Observation: Anger and confusion are more common in traumatic brain injury sufferers in the case of executive control disorders following prefrontal, and in particular orbitofrontal
damage.
Observation: Aggressive behaviour is more common in older men, in the case of speech disorders, in a noisy environment, or within 24 hours following an epileptic fit.
1.2.3. Irritability
1.2.3.1. Definition
Irritability can be defined as an excessive reaction with unjustified outbursts of anger. This term is used in numerous categories of the DSM with no specific definition. Irritable mood is defined in the DSM-IV as "easily vexed and angered", and is for example a characteristic of major depressive episodes. Symptoms include persistent anger, a tendency to react to events with outbursts of anger, accusing others, or feelings of extreme frustration for trivial reasons. Irritability is the main component of hostility.
R7: Irritability can be defined as a disproportionate reaction with unjustified outbursts of anger (EC).
1.2.3.2. Incidence/prevalence
Observation: The incidence of irritability in patients with severe TBI varies between 29 and 71% depending on the studies.
1.2.3.3. Risk factors
Observation: Risk factors for irritable behaviour in TBI patients include loss of employment, social isolation, and depression, and males aged between 15 and 34 years are more at risk.
1.2.4. Abuse and excessive consumption: risky, excessive, addictive behaviour A variety of categories are currently accepted (cf. public hearing: abuse, addiction and multi-substance use: treatment strategies - HAS 2007): "Simple use: any conduct that is not an issue as long as consumption remains low. This notion varies from product to product and is often unclear, as the thresholds have only been defined for alcohol. In some cases, the risk is higher according to the products or the situation (pregnancy, driving, specific psychological factors...). Risky use:
consumption that is likely to induce additional medical, psychological or social damage in the short, medium or long term. Harmful use is characterised by the presence of medical, psychological or social damage induced by the consumption, whatever the frequency and level, and the absence of addiction. Addictive use is characterised by loss of control of consumption. Addiction is not defined in relation to levels or frequency of consumption, or in relation to the complications often associated.
Multi-substance use is defined simply by the consumption of at least 2 psycho-active substances."
In order to examine the links between TBI and addiction, it is important to identify the incidence of abuse or "misuse" of alcohol and drugs prior to the trauma, at the time of the trauma, and following the trauma, and to compare the data with those of the general population.
Alcohol and drugs before the trauma: History of alcohol abuse reported in 18 to 79% of TBI, and history of consumption of illicit drugs in 10 to 44% of TBI.
Alcohol at the time of the TBI: 31 to 51%
In the United States, alcohol is a major factor in TBI.
Studies show that alcohol and marijuana consumption are not predictive of TBI, and TBI is not predictive of post-traumatic substance use (level 2).
Alcohol consumption is associated with more severe lesions in Road Traffic Collisions (RTC) and a greater number of serious accidents.
Alcohol and drugs after TBI: between 1 and 5 years after the TBI, the prevalence of high alcohol consumption or addiction varies from 7 to 26% depending on the studies. Overall, the prevalence of alcohol abuse is lower following a TBI in comparison with before the TBI.
The consumption of illicit drugs after TBI varies from 2 to 20% depending on the studies.
Other substances: The literature review does not provide any information regarding the use and/or abuse of cocaine, stimulants and opioids in the TBI population. Eating disorders are often described after a traumatic brain injury, but the little information found in the literature was generally limited to case studies. These symptoms, and notably hyperphagia, can be integrated in other behavioural disturbances such as the Kluver-Bucy syndrome or endocrine disorders, which are also common after TBI.
Observation: Drug and alcohol consumption before a TBI is not significantly different from that of the general population.
Observation: Following a traumatic brain injury, alcohol abuse affects the severity of the brain damage, the depth of mental derangement, as well as the use of narcotic and psychotropic drugs.
Observation: Drug or alcohol consumption prior to a TBI increases the risk of subsequent behavioural disorders (EC).
Observation: The prevalence of alcohol or illicit substance abuse is minimal in the year following a TBI. However, even if the data from the literature are equivocal, the risk of harmful or addictive use seems to be greater after a TBI and in particular after returning home.
Observation: Additional studies (longitudinal studies) are necessary before any recommendations can be established.
Observation: The risk of addiction, depression or suicide is higher in TBI patients with a history of misuse and the probability of returning to work is lower.
Observation: In TBI patients, low level of education, and low social class, prior consumption, and depression are factors associated with harmful substance use or addiction. In addition, male TBI patients are more at risk.
1.2.5. Behaviour resulting in forensic consequences, misdemeanour, crime
The question regarding a link between TBI and behaviour resulting in forensic consequences is often raised. Several epidemiological studies have investigated the prevalence of prior TBI in prison populations.
Behavioural disorders secondary to a traumatic brain injury can be associated with criminal
behaviour, which in some cases leads to imprisonment. Therefore, a TBI in childhood or adolescence increases the risk of psychiatric disorders (OR=2.1), and in men, a TBI is significantly associated with subsequent psychiatric disorders linked to criminality (OR=4.1) (level 2).
The risk of violent crime is greater in TBI populations (level 2). The risk of committing violent acts depends on the age at the time of the TBI and co-morbidities (harmful use of drug or alcohol). The risk of committing a violent crime is higher in 5.8% of subjects with a TBI and is lower if the TBI occurred before the age of 16.
According to two meta-analyses, the prevalence of a prior TBI was significantly higher in prison populations compared with the general population (level 2). In the first meta-analysis, the prevalence
According to two meta-analyses, the prevalence of a prior TBI was significantly higher in prison populations compared with the general population (level 2). In the first meta-analysis, the prevalence