Autoimmune Movement Disorders

Autoimmune Movement Disorders

Ross Finesmith MD

Sydenham’s Chorea is the most understood autoimmune basal ganglia autoimmune condition associated with a post-infectious state.^1,2 This condition manifests with choreaform movements and neuropsychiatric symptoms. There is immunological laboratory confirmation and clinical therapeutic research studies that support the autoimmune reaction in Sydenham’s Chorea is caused by group A-Streptococcus (GAS) infections.^{3 4 5 6} There is a spectrum of immune mediated basal ganglia disease processes that manifest as neuropsychiatric conditions.⁵ Evidence support that Sydenham’s Chorea and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) are caused by a mechanism of autoantibody mimicry.^1,7

In an effort to clear the body from infection, an individual’s immune system produces antibodies that specifically lock onto GAS surface antigens to neutralize the invader; however in some persons the surface antigens of specific brain cells has a similar cell antigen as the GAS bacterium. These neuronal surface antigens are stimulated by the GAS directed antibody and results in neuronal cell dysfunction which generates abnormal movements. These GAS directed antibodies are reported to cause the clinical symptoms seen in Sydenham’s Chorea and PANDAS.

The abnormal autoimmune response in Sydenham’s Chorea and PANDAS target and damage specific cortical, striatal, thalamic and basal ganglia cells by locking into their surface antigens. The autoimmune attack on these brain cells results in abnormal function, and subsequently, neuropsychiatric symptoms. Identifying and testing for the presence of these antibodies allows for an effective diagnostic panel of tests and may provide insight to more specific therapeutic interventions.

Dopamine (DA) is a prominent neurotransmitter and plays a key role in motor movements orchestrated through both cortical and sub-cortical brain regions. Parkinson’s disease is the most common neurological disorder to be caused by abnormal DA activity. Sydenham’s Chorea, Tourette’s syndrome, tics, autoimmune encephalitis and other neuropsychiatric disease states have been discovered to relate to abnormal DA activity as well.^8,9

There are 5 subtypes of dopamine receptors (D₁-D₅) and each has unique composite, structure and function.¹⁰ The basal ganglia and cortex have a high concentration of receptor types D1 and D2. An animal model of tic behaviors was shown to have significantly increased dopamine D1 receptor activity in the cortical and limbic neurocircuitry.¹¹ In addition, abnormal D2 receptor activity in the basal ganglia has been reported in movement disorders.¹² This correlates with the effectiveness of pharmalogical D1and D2 receptor blocking agents, such as the neuroleptics that effectively suppress chorea and tics.¹³ D2 receptor antibodies have been found in the serum of patients with autoimmune induced movement and psychiatric disorders and there were no D2 antibodies detected in healthy controls.¹⁴ Recent studies have demonstrated that autoantibodies in Sydenham’s’ Chorea and PANDAS specifically cross-react with brain D1 and D2 receptors.¹⁵

It is our current understanding in Sydenham’s Chorea that antineuronal antibodies are generated and cross the blood-brain barrier to induce neuronal dopamine release by activating calcium protein kinase II (CaMKII). This release of excessive DA in the basal ganglia is believed to create the abnormal movements.¹⁶ In addition, studies have reported isolating autoantibodies that bind to neuronal cell gangliosides and intracellular tubulin that play a role in generating abnormal movement patterns as well.¹⁷

It is important to include GAS related autoimmune movement disorders in the differential for motor tics and new onset chorea. A careful history may reveal previous signs and symptoms of GAS infections, such as sore throat and cold-like symptoms. A panel to identify antibody’s associated with PANDA’s and Sydenham’s Chorea includes: anti-dopamine D1, anti-dopamine D2, anti-lysoganglioside, anti-tubulin and cam kinase II neuronal cell stimulation assay. These measurements will support a auto-immune diagnosis and antibiotics will reduce the bacteria load.  With this treatment, antibody levels will gradually be reduced followed by a reduction in the clinical movement disorder.

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17.       Kirvan CA, Cox CJ, Swedo SE, Cunningham MW. Tubulin is a neuronal target of autoantibodies in Sydenham's chorea. J Immunol. Jun 1 2007;178(11):7412-7421.