For one 23-year-old woman, the sudden, uncontrollable flinging of her right arm and leg was just the beginning of a medical mystery that would reveal a fascinating connection between the immune system and the brain's motor control centers.
Imagine waking up one day to find your limbs moving on their own, dancing to a tune you didn't choose. This isn't a metaphor but a reality for individuals experiencing hemichorea - a neurological condition characterized by involuntary, jerky movements on one side of the body. When these movements alternate from one side to the other, doctors term it "alternating hemichorea," a rare phenomenon that led researchers to uncover remarkable insights about how the immune system can influence brain function.
To understand this case, we must first explore antiphospholipid syndrome (APS), an autoimmune disorder that sometimes turns the body's defenses against itself.
In APS, the immune system produces antibodies that target phospholipids - fat molecules that are crucial components of cell membranes throughout the body, including blood cells and the lining of blood vessels 6 .
These rogue antibodies create what doctors call a "hypercoagulable state" - meaning the blood has an increased tendency to form clots 6 .
Neurological Symptoms
Stroke, seizures, and movement disorders
Vascular Complications
Blood clots in arteries or veins
Obstetric Issues
Recurrent miscarriages in pregnant women
When APS occurs without an accompanying autoimmune disease like lupus, it's classified as primary antiphospholipid syndrome 6 . While APS affects many body systems, its impact on the brain reveals particularly fascinating connections between immunity and neurological function.
Chorea gets its name from the Greek word for "dance," describing the irregular, flowing, random-appearing movements that characterize this condition 6 .
The brain circuitry responsible for these movements primarily involves the basal ganglia, a group of interconnected structures deep within the brain that help control and refine our movements. Disruption to this delicate system - whether from stroke, metabolic imbalance, or autoimmune activity - can result in the uncoordinated, involuntary movements seen in chorea.
Age: 23-year-old woman
Symptoms: Episodes of uncontrollable movements on alternating sides of her body
Year: 1994 1
What made this case particularly significant was how doctors investigated it using positron emission tomography (PET) scanning to measure brain metabolism during different phases of her condition:
When her left side was unaffected
6 months later, when she had no symptoms
2 months after the asymptomatic scan
The research team employed 18F-fluorodeoxyglucose (FDG) and PET imaging, a technique that measures glucose metabolism in different brain regions 1 . The method works on a simple principle: more active brain areas consume more energy (glucose).
Structures within the basal ganglia - the caudate nucleus and lentiform nucleus (which includes the putamen and globus pallidus) - known to be involved in movement control.
The PET scans revealed a striking pattern: during episodes of hemichorea, the contralateral (opposite-side) striatal structures became significantly hypermetabolic 1 .
| Scan Timing | Striatal Metabolic Findings | Clinical Correlation |
|---|---|---|
| Right hemichorea | Left lentiform metabolism increased by 19% (>3 SD) | Hypermetabolism contralateral to symptoms |
| Asymptomatic period | Right caudate metabolism increased by 20% (>3 SD); other striatal regions normal | Unexpected hypermetabolism despite no symptoms |
| Left hemichorea | Right caudate and lentiform metabolism increased by 33% (>3 SD); left caudate also elevated | Bilateral but asymmetrical changes, predominantly contralateral |
These findings demonstrated that hemichorea in APS correlates with increased metabolic activity in the basal ganglia opposite to the symptomatic side of the body. Perhaps even more intriguing was the discovery that striatal hypermetabolism could persist during asymptomatic periods, suggesting ongoing subclinical changes in brain function 1 .
Understanding APS-related chorea requires specialized tools and techniques. The table below highlights key resources mentioned in the literature:
| Research Tool | Function in APS-Chorea Research | Example from Case Study |
|---|---|---|
| FDG-PET Imaging | Measures regional glucose metabolism in the brain; identifies hypermetabolic areas | Revealed striatal hypermetabolism contralateral to symptoms 1 |
| Antibody Testing | Detects and measures specific antiphospholipid antibodies | Identified elevated anticardiolipin and anti-β2-GPI antibodies 5 6 |
| Structural MRI | Rules out visible brain lesions or infarction | Typically normal in APS-chorea despite symptoms 5 |
| Standardized Clinical Assessment | Objectively documents and tracks movement symptoms | Used to correlate clinical state with scan findings 1 |
These tools collectively enable researchers to connect immune system abnormalities with functional changes in the brain, creating a more complete picture of this complex condition.
The discovery of striatal hypermetabolism in APS-related chorea raises an important question: what drives this increased energy consumption?
Antiphospholipid antibodies might directly interact with brain tissue, particularly structures in the basal ganglia, causing excessive neuronal firing and increased energy demands 6 .
The antibodies may disrupt the delicate balance between excitatory and inhibitory pathways in motor circuits. This could "release the brakes" on certain brain regions, leading to overactivity .
While large strokes are uncommon in APS-chorea, there might be subtle vascular changes that impair blood flow to specific brain regions, triggering compensatory metabolic changes 6 .
Increased metabolic activity in the striatum
The prognosis for APS-related chorea is generally favorable compared to degenerative movement disorders. Many patients experience significant improvement with appropriate treatment, and the course is often monophasic rather than progressively worsening 6 .
The alternating hemichorea case from 1994 wasn't just an isolated curiosity. Subsequent research has confirmed that striatal hypermetabolism is a consistent feature in APS-related chorea 5 .
A 2022 literature review that examined 142 cases of antiphospholipid-related chorea found that all cases undergoing FDG-PET imaging showed striatal hypermetabolism - either bilateral in generalized chorea or contralateral in hemichorea 5 .
This growing body of evidence confirms that functional brain imaging can provide valuable diagnostic clues when standard structural MRI appears normal. The distinct metabolic pattern helps differentiate autoimmune chorea from other forms, guiding appropriate treatment decisions.
The story of alternating hemichorea in primary antiphospholipid syndrome illustrates a profound concept in modern medicine: the intricate connections between immune function and brain activity. What might appear as a simple movement disorder reveals itself to be a window into the complex dialogue between our body's defense systems and our neural circuits.
This case reminds us that sometimes the most valuable scientific insights come from carefully studying exceptional patients - those whose symptoms defy conventional explanation but ultimately illuminate pathways to understanding broader principles of human health and disease.
As research continues, each unusual case adds another piece to the puzzle of how immunity shapes brain function, bringing us closer to better treatments for those living with these challenging conditions.