Introduction

Batten disease or neuronal ceroid lipofuscinosis (NCLs), is a group of neurodegenerative disorders.¹ These disorders affect adults and children and are sorted together by similar clinical features such as a decline of motor, visual and mental functions, epileptic seizures and unfortunately, premature death.^2,3 Traditionally, the disorders were classified into age of symptom onset: infantile (first year of life), late infantile (typically between ages 2 and 4), juvenile (typically between ages 5 and 8) and adult.² However, during the 1980s and 1990s, there were case studies that suggested other ages of onset existed.² This includes a late infantile variant and an early juvenile.^2,4,5

Definition and classification 

A general definition of this disease is “a progressive, degenerative disease of the brain”.² Identifying symptoms as soon as possible, will improve the quality of life for both the affected person and their family.

The classification system for Batten disease is dependent on the age of the symptom onset.  These are present as a result of genetic defects in a specific gene(s). Environmental factors and additional disabilities can worsen the disease.² An early diagnosis can facilitate a proper management of Batten’s disease, through adequate intervention,  counselling and support for children and their families.⁶

Epidemiology and prevalence

Batten disease can affect all ethnicities and ages around the globe, with estimated rates of incidents that range from 2 to 13 of 100,000 live births.⁷

According to Cialone et al., (2012), Batten disease is usually spotted in people assigned male at birth (AMAB) first. On average, people assigned female at birth (AFAB) were often diagnosed a year later in comparison to people AMAB.⁸

Genetic basis and inheritance patterns 

Batten disease has at least 14 different NCL genes that are involved.⁹ The majority of these genes are stored in the lysosomal pathways.¹⁰ The genes are mutated and cannot carry out their intended purpose, which leads to the loss of neurons in the brain.³

In most cases, the disease is inherited (passed down to the offspring) recessively. There are exceptions to this, which studies such as Nosková et al., (2011) have found to be dominantly inherited.¹¹

For more information regarding Batten disease, please refer to this article: What is Better Disease?

Cognitive changes in batten disease

Early cognitive symptoms 

A typical patient suffering from Batten’s disease may be a child with loss of vision, dementia and/or epilepsy.¹² The most common symptom that is recognised the earliest, usually is the loss of vision, with a rapid progression to blindness.

In 1902, Frederick Batten presented a pair of siblings, with similar clinical features. The girl aged around 6 years “…became spiteful at school, had attacks of violent temper…her sight was failing”. The older sister, aged 10, had also experienced vision loss and seizures and was living in an asylum because her “mental condition…deteriorated.” This showed the most common symptoms of the disease: vision loss, behavioural symptoms and cognitive decline, in one of the earliest cases recorded.¹³

Symptoms

Studies have shown impairments in verbal intelligence, attention, memory, language, motor speed, and dexterity.¹ Speech and comprehension abilities seemed to be less developed compared to unaffected children, yet, not as impaired as other areas mentioned above.¹⁴ The severity of Batten disease was variable amongst the patients, therefore, the rate of decline was also variable.¹⁴

Learning difficulties 

Learning difficulties were identified because of the patients' memory issues and motor speed difficulties. A study showed that after children reach 10 years old, learning Braille becomes very difficult. When learning this ability early as a child, the patients continued to be able to use it later in life.¹³ This demonstrates the effect of learning and retaining information, linking it to memory impairments and cognitive decline.

Progressive cognitive decline 

Batten’s disease has shown a significant trend of cognitive decline in all patients. As shown by research, the loss of memory and attention progressed from children into their teen years.¹⁴ There is also a loss of communication abilities and mobility such as the capacity to feed by themselves. This illustrates the shift between an already significant impairment to something even more severe. A repeated assessment using intelligence tests showed the change in cognitive functions over time.

Assessment and diagnosis

While assessments, such as the Wechsler Intelligence Scale for Children - Fourth Edition and other intelligence tests help with evaluating the skills the children have, when their disease progressively gets worse, the tests are limited.¹³ This is through the mass decline of cognitive functions, such as loss of speech, that prevents the children from providing a verbal response to a language task.¹²

Neuropsychological testing 

The Unified Batten Disease Rating Scale is used to assess physical, behavioural, and functional capability in juvenile NCL. This instrument of measure was developed to evaluate cognition at the point when a child can no longer perform a task. This is important because the common symptoms of Batten disease – loss of vision and difficulty in speech – can make it hard for the usual intelligence tests to be used. This scale improves on the assessments that are carried out.¹⁵

Behavioural changes in batten disease

Early behavioural symptoms 

A study analysing 42 children with Batten disease found high rates of physical restlessness (35%), aggression (40%), fears (45%), and sleep problems (30%). 10% of these children also experienced psychotic symptoms (hallucinations and/or delusions), depression, and irritable mood.^13,16

A behavioural study by Dolisca et al. (2013), used the Child Behaviour Checklist on 30 children. This instrument measured anxious/depressed mood, withdrawn/depressed mood, somatic complaints, social problems, thought problems, attention problems, rule-breaking behaviour, and aggressive behaviour, in the children with Batten disease. Significant difficulties were found in attention problems and aggression.¹⁵

Johnson et al. (2019) showed in the table below, what the common behaviours are in each of the affected NCL genes:

There are still a few genes that are undetermined in regard to behaviour, but otherwise, this illustrates the relations between certain genes.¹⁷

Progression of behavioural issues 

Using the Child Behaviour checklist, a graph was made, which plotted the data of children suffering from Batten’s disease, and their relation with aggressive behaviour.¹³ This graph shows a curve in the line, where the aggressive behaviour rises as the age of the child increases, and therefore, the disease progresses. Then the aggressive behaviour declines at a certain age, and the disease worsens. This suggests a cognitive decline, reducing certain behaviours - such as aggression.¹³

Impact on daily living and social interactions 

These behavioural symptoms negatively affect the child and their family or caregivers, even people from other settings, such as school/work. Symptoms are overwhelming to those around and families suffer in many ways. Considering the recessive nature of the disease, other family members might also be affected by the disorder. Unfortunately, children suffering from Batten disease will deteriorate over time and often die prematurely.¹⁸

Management and therapeutic approaches

Symptomatic treatment 

Treatment usually targets the cognitive symptoms, it improves memory and treats behavioural symptoms, such as depression, anxiety and aggression.⁶ However, the treatment acts more as a symptom relief rather than a cure of the underlying issue – the Battens disease itself.

Supportive care

Wright mentions the importance of multidisciplinary teams when it comes to supporting patients suffering from Batten's disease. The first point of contact was mostly through an ophthalmologist, then an orthoptist and a general practitioner. This illustrates the value of having a starting point when there are abnormalities in a child's vision. There were even mentions of a few cases regarding parents and a teacher who were able to identify something distinctly wrong with a child. This level of care makes up a team with an ophthalmologist, a paediatrician and a primary caregiver.⁶ 

Experimental treatments and research 

Gene therapy 

Gene therapy is a treatment for Batten disease that is being explored, where a corrected copy of the genes that have been mutated in the patient, would be inserted.¹⁷

Clinical trials and emerging therapies

Data from Dolisca et al. (2013) has shown that if the child with Battens disease had greater behavioural symptoms, there was an association with lower family/parent functioning, in comparison to the standard family dynamics. This implies that environmental factors can influence the severity of behavioural symptoms. Additional research suggests how siblings of children who did not have Batten’s disease were associated with higher levels of anxiety and social withdrawal. This shows the support needed on a holistic level for the family.¹⁵

Summary 

Batten disease is a genetic neurodegenerative disorder affecting children and adults. Cognitive changes in Batten disease include impairments in verbal intelligence, attention, memory, language, motor speed, and dexterity, and a weaker ability in speech and comprehension. There is a significant cognitive decline that can occur rapidly based on the affected gene and the environmental factors. 

Behavioural changes in Batten disease include physical restlessness, aggression, fears, sleep problems, psychotic symptoms (hallucinations and/or delusions), depression, and irritable mood. Symptoms, such as aggression, can change over time. The aggression increases as the disease progresses, and then ameliorates when the patient suffers a cognitive decline. 

Managing these changes can be difficult. Building up a trusted team can help with these changes, especially when it comes to maintaining a supportive environment for the patient and their family.