Managing Key Symptoms

CLN2-specific care aims to maintain function for as long as possible and improve quality of life

Seizure management1,2

The goal of CLN2 seizure management is to maintain function by decreasing the frequency and severity of seizures, while balancing side effects. Even though efforts are made to minimize the impact of seizures on the well-being of the child, a complete elimination of seizures is unlikely and some seizure activity may occur. Management strategies for seizures should be assessed on a case-by-case basis and will vary depending on the stage of disease progression.

To help achieve this goal, CLN2 disease experts recommend the following for consideration:

  • Using as few anti-epileptic drugs (AEDs) as necessary—most often, 2-3 AEDs are used in combination for seizure management
  • Educating families on fall safety to help them be prepared for the next seizure and how to minimize injuries
  • Setting expectations with families for the possibility of some seizure activity to help them become as comfortable as possible with any seizures their child may experience
  • Distinguishing epileptic seizures from pain and other nonepileptic movements like myoclonus, dystonia, dyskinesia, chorea, and tremor is helpful to determine appropriate management
  • Considering a ketogenic diet, which may be helpful in the control of refractory seizures

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  • Some commonly used AEDs are used in CLN2 disease
    • However, some of these AEDs may be problematic for children with CLN2 disease and should be used with caution, as they may exacerbate myoclonic seizures, nonepileptic myoclonus, or existing symptoms of the disease
  • In CLN2 disease, seizures become treatment-­refractory and experts move to combination therapy in response
  • When managing seizures related to CLN2 disease, it should be noted that:
    • It is important to regularly reassess medications, particularly when there is a new symptom or an acute change. Apparent signs of disease progression can at times be adverse effects of medications

Caution should be taken when using certain AEDs in CLN2 disease. Some medications may exacerbate existing symptoms or have different secondary reactions in children with CLN2 disease.

Movement disorder strategies

In CLN2 disease, movement disorder is characterized by severe myoclonus (both epileptic and non-epileptic), and accompanied by dystonia and spasticity. These are the 3 most prominent movement disorder symptoms and are generally difficult to control. Symptoms like chorea, tremor, and ticks have also been observed.3,4

These movement disorder symptoms are difficult to control, and the overall goals should be to diminish their frequency and severity; maintain range of motion, posture, and function; prevent pain; and maintain quality of life.1

Myoclonus

  • AEDs can be used to manage epileptic and non-epileptic myoclonus by reducing activity to an acceptable level
  • Non-pharmacologic support, like physical therapy can help children with motor rest and enable better sleep, while also influencing bodily functions such as metabolism, temperature regulation, communication, and anxiety
    • Pressure toward a proximal joint helps, and the child can be placed on their affected side to find relief
    • Body weight can have a regulating effect, as can application of a weight blanket

Dystonia

  • Posturing techniques can support the best possible function of the child, including independent sitting and eating
  • Adaptive equipment with good stabilization can be used to allow for torso motor rest
  • Lateral pillows provide relief and a therapy chair with vest can provide neck support
  • For individual joints, tight bandages can enable regulation of muscle tone and improvement of body perception
  • When dystonic crisis occurs, consider all etiologies, including pain, constipation, and side effects of seizure medications

Spasticity

  • Facilitation of movement and stretching helps maintain the mobility of major joints
    • Manual techniques include slow and long-held stretching and pressure to bases such as palm or foot
    • Weight shifts to the restricted joint pressure points, which reinforce the spasticity, should be avoided
  • Tolerance of equipment should be assessed to enhance orthotic fit and prevent secondary skin complications

Pain management strategies1

Experts highlight the importance of differentiating pain from other symptoms, like boredom, anxiety, fear, or depression, to be able to appropriately manage it.

  • The most common causes of pain involve contractions/dystonia, spasticity/positioning problems, dystonic crisis, constipation, and side effects of AEDs
  • Others include reflux, urine retention, skin breakdown/sores, myoclonus, and peripheral neuropathy

Because children in later stages of the disease are nonverbal, parents are often best able to read their children’s cues to help with pain assessment.

  • While experts agree many different clinical tools exist to measure pain, none are specific to CLN2 disease and providers should always value the opinion of families when assessing pain

Experts also recommend use of other pharmacologic and non-pharmacologic therapies including heat, use of positioning aids, and physiotherapy.

Nutritional and gastrointestinal management strategies1

Feeding, Dysphagia, and Respiratory/Gastrointestinal (GI) Complications

Providing a balanced diet while managing swallowing difficulties, preventing aspiration and constipation, and controlling reflux are essential in CLN2 nutritional management1

Assessing weight management and nutritional status at least every 6 months, or more frequently to monitor appropriate growth

  • Vitamin and mineral supplementation may be required for the child's health

Frequent evaluation of feeding and swallowing when the child is still taking food orally

  • Parents should be advised of food consistency, positioning, and monitoring for excess saliva and progressive dysphagia while feeding to prevent aspiration
  • Pharmacologic and non-pharmacologic therapies can help manage secretions. Recommended therapies include suctioning, oral care, corn whiskers tea, and speech, feeding, or physical therapies
  • Pneumonia due aspiration, cardiorespiratory failure, and sepsis are the most common causes of death in the children with CLN2 disease and aggressive management and prevention of aspiration is recommended
  • Speech and feeding therapy, along with physical therapy to improve posture, may be of benefit and are also recommended by experts

Considering alternative methods of nutrition (feeding tube) and the timing of the recommendation depends on the views of the family and the needs of the child

  • Feeding tubes are most often considered when weight loss occurs, risk of infection is high, or administration of oral medications becomes difficult
  • Timing for introducing a feeding tube (nasogastric or gastrostomy) is an important consideration
    • Begin this discussion with care, taking into consideration that caregivers may be sensitive to this step, as it can signal more advanced disease
    • Families may consult with their child's clinician and dietitian to help make important feeding tube decisions, like continuing to provide home-cooked food and whether it is still safe to feed by mouth
    • Earlier placement can prevent fatigue of the child due to length of meals

Providing guidance for managing GI symptoms, such as constipation and gastroesophageal reflux

  • Constipation is a common GI symptom that can lead to dystonic crises and can be addressed through various management strategies including monitoring dietary and fluid intake, laxatives, and suppositories
  • Gastroesophageal reflux can be addressed by strategies including thickening of fluids or antacids

References: 1. Williams RE, Adams HR, Blohm M, et al. Management Strategies for CLN2 Disease. Pediatr Neurol. 2017 Apr;69:102-112. doi: 10.1016/j.pediatrneurol.2017.01.034. 2. Johannsen J, Nickel M, Schulz A, Denecke J. Considering valproate as a risk factor for rapid exacerbation of complex movement disorder in progressed stages of late-infantile CLN2 disease. [Epub ahead of print April 4, 2016]. Neuropediatrics. 2016 Jun;47:194-196. doi: 10.1055/s-0036-1579784. 3. Chang M, Cooper JD, Davidson BL, et al. CLN2. In: Mole S, Williams R, and Goebel HH, eds. The neuronal ceroid lipofuscinoses (Batten Disease). 2nd ed. Oxford, United Kingdom: Oxford University Press; 2011:80-­109. 4. Mole SE, Williams RE. Neuronal ceroid-‐lipofuscinoses. 2001 Oct 10 [Updated 2013 Aug 1]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews®.