PANDAS

PANDAS – Paediatric Autoimmune Neuropsychiatric Disorder associated with group Streptococcus, is a condition seen in the paediatric population consisting of tics or obsessive compulsive disorder exacerbated or brought on by a common bacterial infection called Group A streptococcus (GAS). This infection may initially present with a sore throat or chest infection with the subsequent onset of neuropsychiatric symptoms (tics and obsessive compulsive behaviours).

This group of disorders has been given ICD-11 code 8E4A.0  by the World Health Organisation but despite this there is resistance to accepting it as a diagnosis by some medical practitioners in the UK. An audit done in 2018 by The Children’s e-Hospital showed that 90% of GP’s were unfamiliar with this condition.

This group of disorders is thought to occur after the body produces an antibody to fight a common everyday infection.  This antibody then goes on to stimulate a part of the brain called the basal ganglia which is involved with movement control (or regulation of obsessive compulsive behaviours) and this results in the abnormal movement, feeling or compulsion that the patient experiences.

PANS (Paediatric acute-onset neuropsychiatric syndrome)  describes a clinical syndrome that may be caused by noninfectious or infectious triggers.  Proposed diagnostic criteria for PANS include: the sudden onset of OCD or severely restricted food intake,  severe neuropsychiatric symptoms (eg, anxiety, depression, emotional lability, etc) or symptoms not better explained by a known neurologic or medical disorder. The key words in this are “sudden onset”. Symptoms appear dramatically and there is a rapid shift in the child’s behaviour.

Background

Rheumatic fever has been a less commonly recognised condition over the past 30-40 years. Part of the diagnostic criteria for rheumatic fever included a condition called “Sydenham’s chorea” or ‘St. Vitus dance” . This was an abnormality of movement which was associated with streptococcal infection. Individuals diagnosed with rheumatic fever were given long term prophylactic penicillin to treat the condition and prevent disease relapse.

Dr Susan Swedo during her research into Sydenham’s chorea realised that there were a sub-group of patients with tics & obsessive-compulsive behaviour that had a sudden onset of symptoms. This was very different to the movements seen with rheumatic fever. Crucially the symptoms had a very rapid pace of onset.

Signs & symptoms

PANDAS symptoms typically start abruptly, almost as if a switch has been thrown. Symptoms include tics, sleep disturbance, obsessive compulsive behaviour, deterioration in handwriting, eating disorders (including anorexia but the problems appear to be more centred on difficulty in coordinating swallowing), behavioural regression and urinary incontinence. By definition these occur following a streptococcal infection which then results in the stimulation of antibodies which stimulates the part of the brain involved in movement and behaviour regulation (the basal ganglia). Examination of the child reveals a child who is “trapped” or “psychologically burdened”. They may have reduced muscle power and may show abnormal movements.

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is defined by the rapid onset of obsessive–compulsive disorder (OCD) or eating restrictions and comorbid symptoms from at least two of seven categories:

  1. Anxiety (particularly separation anxiety)
  2. Emotional lability or depression
  3. Irritability
  4. Aggression, and/or severely oppositional behaviors
  5. Deterioration in school performance related to ADHD-like behaviors, memory deficits, and cognitive changes
  6. Sensory or motor abnormalities
  7. Somatic signs and symptoms, including sleep disturbances, enuresis, or urinary frequency (Swedo et al. 2012; Chang et al. 2015). Acute onset cases that are triggered by Group A streptococcal infections may meet diagnostic criteria for both PANS and PANDAS.

The Children’s e-Hospital PANDAS Clinical Model

The Children’s e-Hospital PANDAS Model has been determined by analysis of over 200 patients with PANDAS who were treated by The Children’s e-Hospital. This data and model were presented at the SANE PANS/PANDAS conference in Malmo, Sweden in October 2019.

Sub-groups

The analsis of the data by the Children’s e-Hospital has revealed ten sub-groups each with their own features and/co-morbidities. These sub-groups are based on phenotypic (including laboratory data differences) between the different groups.


This sub-grouping will be used as a framework for further data gathering to enhance our undestanding of PANDAS.

Diagnosis

Criteria for diagnosis of PANDAS include:

  1. Prescence of OCD and/or Tics
  2. Pre-pubertal onset
  3. Acute onset of symptoms with an episodic pattern
  4. Association with a neurological abnormality
  5. Temporal relationship with Group A strep infection (Determined by a raised ASO titre, Anti-DnaseB or isolation of group A streptococcus from a throat or skin swab).

Examination of the child should include looking at the throat, ears, skin (eg for impetigo or guttate psoriasis), examining the peri-anal area and genitals for infection, checking for a heart murmur and assessing weight and height.

Investigations

Having the right investigations to approach the management and treatment of a child with PANDAS is essential. Our experience has shown that there is variabilty  between laboratories and that using the right laboratory is important. The investigations that we recommend are available to health care professionals through our Virtual Medical School (postgraduate section). It is important to look at the child as a whole and aim to optimise the health of the child. This will include looking at conditions such as allergy.

Disease monitoring

You can download the symptom diary by clicking on the following link; PANDAS symptom monitoring chart. This scoring sheet also allows  parents to add detail such as whether or not a child is receiving antibiotics or anti-inflammatories. This information is invaluable in assessing the patients that we see using the Children’s e-Hospital on-line service but can also be used to help parents with any health professionals they see.

Treatment of PANDAS

Treatment can be divided into several stages which are described below.

  1. Induction of disease remission

    • Anti-inflammatory treatment
      • Non-steroidal anti-inflammatory drugs (eg ibuprofen). This must be used with caution in patients with asthma and also only used with medical supervision during the coronavirus pandemic.
      • Steroid pulse therapy (e.g. prednisolone). It is important to determine if the patient has had chicken pox previously before embarking on a prolonged course of steroids. This treatment is usually started by a tertiary level paediatric neurologist.
    • Antibiotic treatment
      • Azithromycin (Zithromax)
      • Penicillin V
      • Cephalexin
      • Amoxicillin
      • Co-amoxiclav (Augmentin)
    • Intravenous immunoglobulin
      • Intravenous immunoglobulin (IVIG) can be used to induce disease remission. Drs. Perlmutter and Swedo used IVIG in the 1999 study published in the Lancet where nearly all of the children benefitted from its use. The sampling was small (30 of children). In PANDAS an autoimmune irregularity is causing encephalitic-like inflammation and the use of IVIG interrupts this process. The PANDAS IVIG study (run by the PANDAS physician network) administered 1gram/kg of the child’s body weight per day on 2 consecutive days. Preliminary results were positive but not conclusive. Prophylactic antibiotics should be continued thoughout treatment if IVIG is given. Currently IVIG is in short supply in the UK  and therefore this treatment is becoming more difficult to offer in the UK.
    • Plasmapharesis
      • In this process the harmful auto-antibodies are removed from the blood system itself. This procedure is not regulalrly offered in the UK.
  2. Cognitive behaviour therapy

    • The onset of PANDAS or PANS symptoms can be extremely distressing for the child and family members. It is therefore essential that psychological support with cognitive behaviour therapy (CBT) is initiated at an early stage. On-line CBT in children has been shown to be more effective than face to face therapy and also allows flexibility in seeking consultations. Using CBT gives parents the tools to manage their child during a crisis.
  3. Comprehensive Behaviour Therapy for Tics (CBiT)

    The main thrust of treatment for Tics (particularly in patients with PANDAS or PANS) is the use of antibiotics, anti-inflammatory and psychotropic drugs. However, Thenemann et al (2107) noted that “while underlying infectious and inflammatory processes in PANS and PANDAS patients are treated, psychiatric and behavioural symptoms need simultaneous treatment to decrease suffering and improve adherence to therapeutic intervention. Psychological, behavioural, and psychopharmacological interventions tailored to each child’s presentation can provide symptom improvement and improve functioning during both acute and chronic stages of illness” Thienemann and colleagues (JCAP 2017)

    CBiT is a therapy that is used to teach people with Tic’s ways to manage them. It is not a cure for tics, but it has been proven to help reduce the number, severity and impact of tics.

    CBIT (pronounced see-bit) is made up of six strategic therapeutic components.

    It is usually offered in a block of 10 weekly sessions.  (although fewer/ more might be necessary) but this can depend on the person with tics and the therapist.

    The success of CBIT comes from the comprehensive combination of therapies used within treatment, these consist of Psychoeducation, Self-awareness training, Relaxation training, Establishing a tic hierarchy, selecting a target tic and reverse engineering it, Formulating a competing response to the target tic using habit reversal techniques, and Social support.

    CBIT is recommended as a first line intervention for tics by the American Association of Neurology.

    The main component of CBiT is Habit Reversal Therapy (HRT). HRT is the most researched validated behavioural therapy for Tics to date, the research stems back to the 1970’s. HRT treats tics individually unlike other behavioural therapies used to treat Tics. You will work on becoming more aware of how a certain tic is expressed, then you learn to do a competing response. You do this by contracting a group of muscles that make it impossible to do the tic at the same time, as soon as you feel the urge coming on, you need to do the competing response and keep doing it even after the urge passes. Eventually you learn to take control of the tic.

    There can be an uncomfortable sensation to begin with but with lots of practice it gets easier.

    To learn how to do this, strategies are used to increase the need for you to tic, making the urge as strong as possible and then you will work at implementing a competing response to make it hard for your tic to break through.

    HRT is hard work and takes time and lots of practice however HRT has been proven to reduce tics by up to 40%

    There are 5 rules when considering competing responses. The competing response must be able to be done anywhere, be done with no props, can be actioned for more than 1 minute, it must be incompatible with the tic and should be more socially acceptable.

    A second method is called Exposure Response Prevention (ERP).  The main aim of ERP is for you to learn to tolerate the urge that comes before a tic, by learning to tolerate the urge you are learning to suppress the tic.​ This can also be hard work, and an uncomfortable sensation to begin with but with lots of practice it gets easier. By exposing your tics, you practice resisting the urge for longer and longer periods of time, until you can stop it in most situations for a period of time. Evidence suggests that ERP is as effective as Habit Reversal Therapy. ERP is best suited to individuals who have a range of troublesome tics or are young. Tic reduction is the result.
    You can book either a single CBiT session or a package of 10 sessions with our CBiT therapist Sarah Sharp by using our online booking site.

  4. Maintainance therapy

Once disease remission has been achieved the antibody level will gradually fall and symptoms will slowly improve unless the immune system is restimulated eg with another infection.

Long term antibiotic use is not without consequence. It is important to limit the amount of antibiotic that your child receives to a minimum, thus avoiding problems such as clostridium difficile infection.This must be coordinated with the help of your GP, neurologist or paediatrician. The practice in the United Kingdom is much more conservative compared with the US and there is much more emphasis on antibiotic stewardship. Despite this conservative approach our results from the Children’s e-Hospital most recent audit show that nearly three quarters of our patients show a good response to treatment.

Authored by: Dr Tim Ubhi

Published: 7th March 2019

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