Dr Hendriksen described the current difficulty with knowing which mental health assessment tools to use in the DMD population. Currently, there is no consensus on which tools are most appropriate for assessing non-motor problems in DMD. A review of tools used for assessing behavioural and psychosocial functioning across all ages in DMD and Becker muscular dystrophy (BMD) found that 61 instruments were used across 54 studies (Hellebrekers et al. 2019). However, the most commonly used instruments are not designed with DMD in mind and do not take into consideration the motor and physical aspects found in boys with DMD. This can result in false negative assessment results for attention deficit hyperactivity disorder (ADHD) for example, with comorbidities therefore being overlooked and under-reported.

The interest in the impact of dystrophinopathies on the brain is a burgeoning area. The original work of the French neurologist, Duchenne de Boulogne, who first described DMD, already made reference to neurocognitive comorbidities, such as low intelligence, epilepsy and obsessive behaviour. Despite this early recognition, treatments for DMD and clinical trials have been directed at skeletal muscle, the heart and other organs, and have tended to neglect brain-related comorbidities. However, there is now growing interest and research into brain involvement in the dystrophinopathies (Hendriksen et al. 2020). An EU multicentre study is currently underway looking specifically at brain-related comorbidities in DMD (BIND study; www.bindproject.eu). Part of this work will be to develop questionnaires likely to be helpful in future for screening for many non-motor comorbidities.

There is a range of neurocognitive, neurobehavioural and neuropsychiatric difficulties associated with DMD. Alongside these difficulties, there are also cognitive strengths, such as visual processing and receptive vocabulary. Dr Hendriksen presented a heuristic model – the ‘Big 10’ – to capture this complex overlap of different brain-related diagnoses. He and his team identified 10 areas of difficulty considered important in understanding learning and behaviour functioning in DMD (Hendriksen et al. 2020). The model categorises problems in four domains: cognition (automatisation, working memory, and attention), learning (dyslexia and dyscalculia), emotion (anxiety and depression) and behaviour [autism, ADHD and obsessive compulsive disorder (OCD)] (Figure 1). Whilst the domains are described separately, in clinical practice there is a complex overlap amongst the 10 areas and it is rare to see an individual presenting with just one difficulty. The model can help clinicians to consider hidden areas of seemingly minor problems, which may co-exist with the more obvious major problems. As such, it was proposed that the Big 10 model may help as a tool to better define and characterise the nature of problems to be considered. Dr Hendriksen is working with Duchenne Parent Project to operationalise this further.

Fig. 1

Figure 1.  

The Big 10 model of non-motor problems in DMD (kindly provided by Dr Jos Hendriksen).

Dr Hendriksen described psychosocial adjustment as being about coping and stress, which is related to perception. He gave an example of the differing perspectives boys with DMD may have on obtaining their first powered wheelchair: some may perceive it as a loss of function, whereas others may perceive it liberating, enabling them to participate in more activities. People with DMD face a range of physical losses across their lifespan, such as the loss of walking, arm function and breathing. Fatigue, poor endurance and bodily pain are common daily experiences. They are also faced with psychological stresses, such as learning to ask for help and having to wait for help. These are important psychological skills to develop when they are young to support their psychological adjustment.

An easy-to-administer instrument that has been validated in DMD populations to screen for psychosocial adjustment from childhood into adulthood is the Personal Adjustment and Role Skills Scale (PARS), which is recommended in the SoC for parents of children aged 5-17 years (Birnkrant et al. 2018). The validity and reliability of the tool for use in boys with DMD was reported 14 years ago (PARS-III) (Hendriksen et al. 2008). Since then, as part of the BIND study, the instrument has been developed for use with adults (PARS-A) (Weerkamp et al. 2022a).

Dr Hendriksen presented unpublished data on using the PARS-III to look at psychosocial adjustment over age. As boys with DMD grow older, he found that their adjustment improved. Psychological adjustment levels were the lowest at ages 6 to 10 years possibly because this is the phase during which they must accept and adjust to the diagnosis and its consequences.

Dr Hendriksen highlighted another important psychosocial issue to consider: learned helplessness, which may lead to ineffectiveness, apathy and not doing anything. Boys with DMD are at risk of learned helplessness because they may put a lot of effort into doing something without achieving a tangible result. He gave the example of having intensive therapy with leg braces which did not lead to improvement. As the boys do not experience tangible results from their performed actions, it is important to create an ‘action–effect–affect chain’, whereby you do something, which has an effect, which then results in an affect or emotion. This approach can be useful to help build self-esteem and prevent learned helplessness.

Dr Hendriksen discussed what is known about neurocognitive functioning in DMD, in the areas of intelligence, working memory and automatisation.

A review of 32 studies between 1960 and 1999, comprising 1224 boys with DMD, found that intelligence levels fell within the low average range (FSIQ of 80) (Cotton et al. 2001). However, in this review, eight different instruments for measuring IQ were clustered together and analysed. Dr Hendriksen and colleagues re-analysed all the data published on intelligence testing in adults and boys, but looked only at those studies using the Wechsler intelligence scales, which are the most used intelligence tests from childhood to adulthood. Data analysed from 43 studies, with 1427 boys and men, from 1960 to 2022, confirmed that the average IQ is below average (FSIQ of 84) (Weerkamp et al. 2022b).

Assessing general intelligence in isolation may underestimate a patient’s potential. Rather, there are cognitive strengths and weaknesses. In clinical practice, Dr Hendriksen noted many patients have strong visuomotor performance despite their motor handicap. Visuomotor functioning and spatial thinking are often areas of cognitive strength in DMD, as well as receptive vocabulary.

Working memory is a core neuropsychological function. The bottleneck theory of working memory states that all information must be transferred via working memory from short- to long-term memory. It is involved in storing information efficiently and being able to retrieve it. In boys with DMD, working memory is thought to be a core cognitive weakness. This may present as difficulty in retelling a story and difficulty remembering multiple instructions. Teachers often report that the boys are not motivated, while in fact they are not able to quickly switch their attention to move on to the next task if they have working memory problems.

Dr Hendriksen’s research has shown there may be a decline in working memory performance over time (Hellebrekers et al. 2020). However, he noted that this is an area that needs more attention, especially in relation to the genotype and mutations which are linked to working memory. The BIND study may shed light on this question.

An important question is whether training can help improve working memory problems. Dr Hendriksen summarised work from his group which showed that computer training can result in an improvement in working memory and in speed of information processing (Hellebrekers et al. 2022). The intervention involved 30 minutes of training across five days a week, over six weeks. This is an area that needs more attention and more research.

Automatisation is the quick and automatic decoding of signs into sounds and is required for reading and arithmetic. Boys with DMD can have problems with automatisation, which can present as dyslexia and reading problems. Higher rates of dyslexia are found in boys with DMD (27%) compared to the general population (3%) (Hendriksen and Vles 2006). It is important to provide early interventions for dyslexia and arithmetic capabilities so that boys can continue to develop their vocabulary, learn to ask questions, and develop literacy and numeracy skills that are important for adult independence. Tests that can help identify problems with automatisation include those measuring the speed of reading (e.g. word lists) and the speed of naming numbers (e.g. dot counting).

Where the presence of one condition interferes with the recognition of others, it is known as diagnostic overshadowing. DMD can easily overshadow the Big 10 problems. In a recent meta-analysis on five neuropsychiatric disorders (of which five are included in the Big 10: ADHD, autism, OCD, depression, anxiety), there was great variance in prevalence rates of each condition, which could indicate that some of these conditions are being overlooked (Pascual-Morena et al. 2022).

Dr Phillipe Collin, Child and Adolescent Psychiatrist, presented the evidence from a recent scoping review of psychopharmacological treatment in neuromuscular disorders, which reported on five published papers in DMD (Brusa et al. 2022). Two were case reports, two case series and one was an observational study. Most patients were under 18 years, but one study included patients up to age 23.

Included in the review was the first case report of the use of the selective serotonin reuptake inhibitor (SSRI) fluoxetine to treat OCD in a boy with DMD (Hendriksen et al. 2016). They reported a clinically significant and positive effect of fluoxetine in a boy with DMD and co-existent OCD and autism.

A case series of 15 DMD patients, aged 5-23 years, with OCD (Lee et al. 2018) found a clinically significant improvement in 10 of 15 patients using drugs from the SSRI class, including fluoxetine, paroxetine and citalopram. One patient of 15 reported rash, gastrointestinal upset and apathy. Urinary urgency was noted with all SSRIs but paroxetine.

Observational data from 10 boys with DMD and ADHD aged 6-10 years using the stimulant methylphenidate up to a dose of 0.2-0.6 mg/kg/day have been described (Lionarons et al. 2019). In the long term, seven of 10 patients showed clinically significant improvements in inattentive symptoms. There were no reported side effects.

A large retrospective case series reported on 700 DMD patients found high rates of neuropsychiatric symptomatology, primarily emotional/behavioural dysregulation and inattention in more than a third of patients and obsessive-compulsive symptoms in 25% (Darmahkasih et al. 2020). Almost a third required pharmacological intervention and, in this study, the main drug type used was SSRIs, mostly fluoxetine.

Prescribing data from the Center of Neurological Learning Disabilities, Kempenhaeghe was then described. Dr Collin noted that referrals to the centre tend to involve more complex cases due to its national specialism in DMD.

Between 2015 and 2022, the centre treated 35 male DMD patients, all under 18 years. Seven boys were diagnosed with autism (two also with OCD and two with behavioural problems). Fifteen were diagnosed with ADHD, seven with a comorbid behavioural problem, OCD was diagnosed in five patients, and an anxiety disorder in three patients. There were four boys diagnosed with mood disorder, one of them with comorbid OCD and one a comorbid anxiety disorder. One medication was prescribed in 28 cases. Seven patients were given more than one medication, usually to treat comorbidity. The most commonly prescribed medication was the stimulant methylphenidate (primarily used to treat ADHD), given to 22 patients. In two patients, an alternative stimulant, dexamphetamine or its long-acting pro-drug lisdexamphetamine, was used. The non-stimulant drugs clonidine, guanfacine and atomoxetine, also used to treat ADHD, were used on three occasions. Only methylphenidate showed a significant positive effect, which was observed in 10 of 22 patients where it was prescribed. Drugs from the SSRI antidepressant/anxiolytic class were prescribed on eight occasions, with fluoxetine most commonly used (in six patients). In five of the six patients prescribed fluoxetine and in the one patient prescribed escitalopram, a significant positive clinical improvement was noted. The most commonly prescribed antipsychotic medication was risperidone, primarily used for behavioural disturbance, in six patients. One of those patients showed a significant clinical improvement. Benzodiazepines (alprazolam and oxazepam) were prescribed on three occasions, with significant positive effect in the two patients prescribed alprazolam for anxiety.

Regarding safety aspects of prescribing in DMD, Dr Collin reported that all medication was discussed with the cardiologist treating the patient before it was prescribed. In all cases, the cardiologist was happy for treatment to be started. There were no incidences of cardiac side effects in the 35 cases treated. The side-effect profile of the commonly used medications, for example, SSRIs such as fluoxetine and the stimulant methylphenidate, appears to be similar to general psychiatric patients under 18 years. Notably, risperidone was often associated with weight gain and methylphenidate with aggression in some patients.

Data of psychopharmacological treatment in a larger sample of DMD patients from Kempenhaeghe and Leuven University Medical Centres have been combined and were recently published (Weerkamp et al. 2023).

Dr Rory Conn, Consultant in Paediatric Liaison Psychiatry, and Dr Dorothea Bindman, Consultant in Adult Neuropsychiatry, presented evidence on the use of medications commonly prescribed in psychiatric disorders.

It is currently unknown how many young people with DMD in the UK have had a neuropsychology assessment. To understand this more, a service mapping initiative has been started. Findings so far show there are some psychologists in neuropsychology services in the UK who are able to see young people with neuromuscular conditions. However, a large number of families in other regions of the UK are unable to access comprehensive neuropsychology assessment due a lack of funding in these services. A further aspect that is being explored is whether educational psychologists are offering assessments for informing EHCPs and, if so, to ensure that the four different areas to which Dr Hoskin referred are included, especially cognition.

Dr Geagan proposed screening questionnaires that could be of use in paediatric neuropsychology teams. It is important to have parent/caregiver reports and teacher reports, as well as self-reports from the young person with DMD. The process of asking the young person to complete self-reports on how they are feeling should start when they are quite young, within the clinical setting.

The proposed screening measures referred to in the SoC, and also being used in the BIND study, are the PARS-III, as discussed by Dr Hendriksen, and the Strengths and Difficulties Questionnaire (SDQ) (Goodman 2001), which looks at emotional symptoms, behavioural difficulties including hyperactivity, peer relationship problems and prosocial behaviour. Dr Geagan shared a provisional pathway for psychological intervention after administering the SDQ, which is modelled on other stepped care models being implemented in paediatric epilepsy services (George et al. 2021).

The current recommendations in the SoC are that “neuropsychology evaluations should be considered within the first year of diagnosis to establish a baseline” and that “re-evaluations should be done every 2-3 years to monitor developmental progress and response to interventions” (Birnkrant et al. 2018). Clinical judgement should be used to decide when to re-evaluate as, for some young people, this might not be necessary until they are transitioning to secondary school or unless specific cognitive concerns are raised by families or teachers.

A potential barrier to accessing a neuropsychology assessment is lack of provision. In some services, neuropsychology services are only accessible for specific departments, such as neurology. The assessment requires specialist skills by a paediatric (neuro)psychologist. A full neuropsychology assessment is more than cognitive testing and has potential to inform other interventions, such as psychotherapy to reduce distress or liaison with schools to help around behavioural issues. The assessment can also identify prognostic and diagnostic indicators: to help understand what may be contributing to a particular presentation; to identify what the young person may be having difficulty with (e.g. working memory problems); and to highlight what is going well for the young person. Information from the assessment can be useful when consulting with primary and secondary care services, including schools. It is important to have functional and meaningful goals in mind, to consider before an assessment how it might be helpful, and also to think practically about what intervention can be offered afterwards. Data collated across neuropsychology assessments will also be helpful in informing practice-based research, such as the neurodevelopmental trajectory and parental/caregiver needs compared to other health conditions.

The suggested areas to include in a neuropsychology assessment are: general abilities (i.e. IQ), mental health and well-being, along with optional tests to assess specific memory skills, attention skills, executive functioning skills and language skills (see Table 1).

Table 1

There are many tiers within language skills. Some young men with DMD may have good vocabulary, but may struggle to express or understand more complex verbal ideas or concepts. It is helpful to obtain a profile to understand how the young person communicates and what they find difficult, which can inform not only home and school life, but also how clinicians ask them questions. Ideally, speech and language therapy would be involved as early as possible if concerns are present for younger children.

Other considerations when undertaking a neuropsychology assessment are the young person’s level of fatigue, impact of any pain and medication. Selection of tests should take into account reduced motor skills with increasing age.

Following a neuropsychology assessment, the psychologist needs to support the family to understand what that cognitive profile means and how it might help understand the young person’s behaviour better. The psychologist might discuss the cognitive profile and impact of mental health difficulties with clinicians to help them also understand the person’s behaviour. Psychologists may suggest other recommendations to support the young person, such as having a break or exercise, or recommending simplified resources in clinic or school. If cognitive difficulties are highlighted, this should be shared with the school and be part of the EHCP and include within it the young person’s strengths. The results will help guide further intervention, for example, if a talking therapy is indicated, adaptations may be needed to account for highlighted difficulties. This is especially important for informing other services, such as CAMHS, so that, if there are difficulties engaging the young person, the service can better understand and take into account the underlying factors. Tracking change over time to help inform the appropriate support into adulthood is important, particularly around the transition to adult services. Having a neuropsychology assessment in the early years can help identify whether a child has a specific learning difficulty (such as dyslexia), an intellectual disability (i.e. significantly impaired intellectual and adaptive functioning) or a neurodevelopmental condition (such as autism) early on, so that appropriate support can be provided in school and referrals to appropriate community teams can be made.

Future aims of the paediatric psychosocial care project include establishing more indirect pathways to psychologically informed care. This could involve upskilling the local team in more psychosocial aspects of care as well as other local teams to be able to support families. The plan is also to demonstrate the effectiveness of psychosocial interventions and to develop guidelines based on practice-based evidence. A further key outcome is to disseminate findings to increase awareness nationally of cognitive strengths and weaknesses in boys with DMD.