TABLE 1
| PANDAS | PANS | Idiopathic CANS |
|---|---|---|
| 1. Presence of OCD and/or a tic disorder | 1. Abrupt, dramatic onset of obsessive-compulsive disorder or severely restricted food intake | Acute onset before age 18 of behavioral and motor signs encompassing |
| The patient must meet lifetime diagnostic criteria (DSM-III-R or DSM-IV) for OCD or a tic disorder. | 1) Primary criterion | |
| Obsessive-compulsive disorder | ||
| 2. Pediatric onset | 2. Concurrent presence of additional neuropsychiatric symptoms, with similarly severe and acute onset, from at least two of the following seven categories | 2) Secondary criteria |
| 1) Anxiety | 1) Anxiety | |
| 2) Emotional lability and/or depression | 2) Psychosis | |
| 3) Irritability, aggression and/or severely oppositional behaviors | 3) Developmental regression | |
| 4) Behavioral (developmental) regression | 4) Sensitivity to sensory stimuli | |
| Symptoms of the disorder first become evident between 3 years of age and the beginning of puberty. | 5) Deterioration in school performance | 5) Emotional lability |
| 6) Sensory or motor abnormalities | 6) Tics | |
| 7) Somatic signs and symptoms, including sleep disturbances, enuresis or urinary frequency. | 7) Dysgraphia | |
| 8) Clumsiness | ||
| 9) Hyperactivity | ||
| 3. Episodic course of symptom severity | 3. Symptoms are not better explained by a known neurologic or medical disorder | 3. Mono- or polyphasic course |
| Clinical course is characterized by the abrupt onset of symptoms or by dramatic symptom exacerbations. Often, the onset of a specific symptom exacerbation can be assigned to a particular day or week, at which time the symptoms seemed to “explode” in severity. Symptoms usually decrease significantly between episodes and occasionally resolve completely between exacerbations.1 | Such as Sydenham’s chorea, systemic lupus erythematosus, Tourette disorder, or others. | |
| 4. Association with Streptococcal infection | ||
| Symptom exacerbations must be temporally related to Streptococcal infection, i.e., associated with positive throat culture and/or rising anti-streptococcal antibody titers.2 | ||
| 5. Association with neurological abnormalities | ||
| During symptom exacerbations, patients will have abnormal results on neurological examination. Motoric hyperactivity and adventitious movements (including choreiform movements) are particularly common.3 |
Abbreviations: OCD, Obsessive-Compulsive Disorder; PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections; PANS, Pediatric Acute-Onset Neuropsychiatric Syndrome; CANS, Childhood Acute Neuropsychiatric Syndromes.
2 According to Swedo et al12 the association between group-A beta-hemolytic streptococcal infection and neuropsychiatric symptoms should be preferably observed on at least two occasions (i.e., two exacerbations). The time lag between infection and exacerbations may vary within and across individuals, often between several days and a few weeks.
FIGURE 1
Post-streptococcal Neuropsychiatric Disorders (including PANDAS) Might Be Associated with Antineuronal Antibodies.
The molecular mimicry hypothesis is one of the mechanisms through which autoantibodies targeting brain structures might be abnormally produced in these conditions. Not all the autoantigens targeted by these antibodies in Sydenham’s chorea or PANDAS seem, however, to be involved in antigenic mimicry between group A streptococcus and brain cells. Other mechanisms, such as bystander activation or epitope spreading, may also be relevant to the synthesis of pathogenic autoantibodies. Part of the figure adapted from Chervonsky AV. Influence of microbial environment on autoimmunity. Nat Immunol 2010;11:28–35.
FIGURE 2
Hypothesized Immune Regulatory Abnormalities.
Summary diagram of the hypothesized immune regulatory abnormalities in patients with Tourette syndrome (see text for details).
TABLE 2
Summary of Evidence of Immunological Changes in Tourette Syndrome from Case–Control Cross-sectional or Case-only Prospective Studies with ≥10 Subjects per Group
| References | |
|---|---|
| Gene expression profiling of peripheral blood mononuclear cells | |
| Age-related overexpression of genes related to natural killer cell pathways and regulation of anti-viral responses | 76, 77 |
| Cytokine expression | |
| Increased concentration of interleukin-12 and tumor necrosis factor- α in serum during symptom exacerbations | 82 |
| Increased concentration of interleukins 4, 5, 6, and 10 in serum during symptom exacerbations (only statistical trend) | 82 |
| Decreased concentration of monocyte-derived cytokines (interleukin 2 receptor antagonist, soluble CD14) | 78 |
| Immune cell subpopulations in peripheral blood | |
| Increased number of CD4+CD95+ and CD8+CD95+ T-cells | 84 |
| Increased number of CD69+ B-cells | 84 |
| Decreased number of T regulatory cells | 85 |
| Immunoglobulin synthesis | |
| Decreased concentration of serum IgG3 and IgA (the latter in patients fulfilling criteria for PANDAS) | 86, 87 |
| Oligoclonal bands of intrathecal synthesis in the cerebrospinal fluid of 40% of patients with Tourette syndrome | 90 |
| Past medical and family history | |
| Higher rate of maternal history of autoimmune diseases | 88 |
| Higher rate of past history of common allergic illnesses | 89 |