PANDAS

Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a controversial proposed condition, in which it is hypothesised that Group A beta-haemolytic streptococcal infection (GABHS) leads to the sudden subsequent onset of a neuropsychiatric disorder (usually obsessive-compulsive disorder (OCD) or tics) in children.¹ The acronym PANDAS was first cited in 1998 to describe this group of patients.²

Doubt remains about the aetiology of the condition and whether it can be considered an independent disease entity.³

More recently, the term PANS (paediatric acute-onset neuropsychiatric syndrome) has been suggested, as a broader definition that does not rely on the presence of a recent Streptococcal infection as the trigger.⁴

Research has failed to establish a causal link between infection and PANDAS/PANS, and nor has a putative inflammatory or autoimmune pathogenesis been confirmed. As yet, no consistent biomarkers have been identified that accurately diagnose PANDAS/PANS or are reliably associated with brain inflammation. There is also debate as to whether or not PANDAS/PANS is clearly distinct from chronic OCD or tic disorders.⁵

Epidemiology

The incidence and prevalence of PANS and PANDAS is very difficult to determine. It has not been systematically studied, and there is controversy over whether the diagnostic criteria describe a distinct clinical entity. It seems to be rare; one retrospective US-based review estimated an incidence of 1 case per 11,765 person-years in children aged between 3 and 12 years.⁶

Presentation

There is a wide range of variation in symptoms, and symptoms may overlap with almost any other psychiatric condition, making diagnosis challenging.⁷

The most striking feature is an abrupt onset of psychiatric/behavioural problems such as emotional lability, anxiety, night-time fears, hyperactivity and oppositional behaviour with some cognitive deficits. There may be dyskinesias - for example, mild facial or vocal tics.

The condition follows a relapsing and remitting course.

Diagnostic criteria have varied over time with changing definitions of the condition. The original PANDAS diagnostic criteria were:⁷

• Presence of OCD and/or tic disorder according to DSM-IV criteria.

• Prepubertal symptom onset.

• Episodic course, abrupt onset of symptoms or of symptom exacerbation.

• Temporal association with GABHS infection (positive throat culture and/or elevated anti-GABHS antibody titres).

• Association with neurological abnormalities on examination.

The broader PANS criteria are:⁷

• Abrupt, dramatic onset of OCD or severely restricted food intake.

• Additional neuropsychiatric symptoms, at least two or more of the following:

  • Anxiety.

  • Emotional lability and/or depression.

  • Irritability, aggression, and/or severely oppositional behaviour.

  • Behavioural regression.

  • Deterioration in school performance.

  • Sensory or motor abnormalities.

  • Somatic symptoms, including sleep disturbances, enuresis, or urinary frequency.

• Symptoms not better explained by another neurological or medical disorder, such as Sydenham's chorea, systemic lupus erythematosus, Tourette disorder or others.

If overtly choreiform movements develop, the child should be considered to have developed Sydenham's chorea and these children require antibiotic prophylaxis against subsequent GABHS infection.²

Investigations

The diagnostic workup of children with suspected PANDAS or PANS is complex, and should ideally involve multidisciplinary assessment from community paediatrics, Child & Adolescent Mental Health Services, and paediatric neurology, as well as any other relevant specialties.⁵

A 2021 Nordic-UK working group proposed the following diagnostic workup:⁸

• A comprehensive family history, medical, developmental, and psychiatric history, covering prior and present symptoms, and including symptoms related to psychiatric, neurologic, neurodevelopmental, infectious, autoimmune, and rheumatic diseases.

• A detailed somatic and neurological examination by a paediatric neurologist, including motor and cognitive abilities and evaluation for dyskinesia.

• A series of standardized assessment scales and questionnaires, for example, trauma screening, assessment of general functioning, assessment of quality of life, and symptom-specific instruments such as ADHD rating scales and screening for anxiety disorders.

• A throat swab for bacterial culture, and complete blood count with differential, anti-streptolysin-O and anti-deoxyribonuclease B antibodies.

• Bloods for ESR, antiphospholipid antibodies, antinuclear antibodies, immunoglobulin subclasses, coeliac serology, neuronal antibodies, myelin oligodendrocyte glycoprotein antibodies, anti-thyroperoxidase antibodies, thyroid stimulating hormone (TSH) receptor antibodies, TSH, T3 and free T3, complement C3 and C4, angiotensin-converting enzyme (ACE), vitamin D, vitamin B12, ferritin, copper, caeruloplasmin, and cytokines.

• Symptom-guided investigations such as:

  • Mycoplasma PCR from throat swab.

  • Nasopharyngeal aspirate PCR for common viral infections.

  • Urinalysis and culture.

  • Drug screening.

  • Urine metabolite screening for suspected metabolic conditions.

If there is profound deterioration of adaptive functioning and/or abnormal neurological signs such as focal neurological symptoms, chorea, encephalopathy or epilepsy, additional workup may include:

• Lumbar puncture and CSF sampling for cell count, protein, glucose, lactate, Epstein-Barr-virus/cytomegalovirus/varicella zoster virus/herpes simplex virus/Mycoplasma/enterovirus/influenza virus IgG and IgM and PCR, Borrelia IgG and IgM (paired with serum), lumbar opening pressure, neuronal antibodies, IgG index and electrophoresis for oligoclonal bands (paired with serum), cytokines.

• Brain MRI with contrast: structural, diffusion, and FLAIR sequences.

• Standard or sleep EEG.

Management

Management is also controversial. There is little strong evidence to guide management.⁵

The 2021 Nordic-UK working group proposed the following:⁸

• Standard psychological and psychiatric treatment as guided by psychiatric symptoms.

• Treatment of any verified or strongly-suspected ongoing bacterial infection.

• Prophylactic antibiotics or tonsillectomy are not recommended.

• Treatments that are effectively experimental, and should therefore only be used in a research setting or within a highly specialised and dedicated national centre include:

  • Non-steroidal anti-inflammatory drugs.

  • Corticosteroids.

  • Intravenous immunoglobulins.