Is chorea caused by damage to the basal ganglia?

Chorea is Caused by Damage to the Basal Ganglia

Yes, chorea is primarily caused by damage to or dysfunction of the basal ganglia structures, particularly the striatum (caudate and putamen). 1

Pathophysiology of Chorea

• Chorea is characterized by involuntary, flowing, non-stereotyped movements that often possess a writhing quality, resulting from dysfunctional neuronal networks interconnecting the basal ganglia and frontal cortical motor areas 1
• The most common focal MRI abnormality in choreiform disorders involves the basal ganglia (60%), predominantly affecting the anterior caudate and putamen 1
• While chorea can result from systemic illness and damage to diverse brain structures, injury to the basal ganglia appears to be a uniting feature across diverse neuropathologies 2
• The abnormal basal ganglia-thalamo-cortical circuit is considered the pathophysiological basis for many movement disorders including chorea 1

Evidence from Specific Disorders

Huntington's Disease

• Huntington's disease (HD) is the prototypical choreiform disorder and most common cause of chorea in adults 1
• In HD, abnormal aggregates of the huntingtin protein accumulate in the brain, leading to the loss of GABAergic medium spiny neurons, particularly in the striatum 1
• Progressive and disproportionate volume loss of the neostriatum is a hallmark finding on imaging studies in HD 1

Wilson's Disease

• In Wilson's disease, structural abnormalities in the basal ganglia are frequently detected on neuroimaging 1
• MRI typically shows hyperintensity on T2-weighted images in the region of the basal ganglia 3
• Simultaneous involvement of basal ganglia, thalamus, and brainstem (found in 55.3% of cases) is highly specific for Wilson's disease 3

Secondary Causes of Chorea

• Multiple sclerosis (MS) can cause secondary paroxysmal kinesigenic dyskinesia (PKD) when lesions involve the thalamus, lenticular nucleus, globus pallidus, and internal capsule 1
• Calcification of the basal ganglia, including idiopathic basal ganglial calcification and calcification secondary to hypoparathyroidism or pseudo-parathyroidism, may cause secondary chorea 1
• Cerebrovascular disease affecting the basal ganglia, particularly lacunar stroke, can result in hemichorea 4

Neuroimaging Findings

• MRI is the optimal imaging modality for evaluating chorea, with the most sensitive sequences being diffusion-weighted and T2-fluid-attenuated inversion recovery (FLAIR) 1
• Functional MRI studies have revealed abnormal connectivity between the thalamus and motor cortex in patients with movement disorders 1
• In patients with PRRT2 mutations (causing paroxysmal kinesigenic dyskinesia), thalamo-prefrontal hypoconnectivity has been observed, indicating inefficient thalamo-prefrontal integration and dysfunction of motor inhibition 1

Diagnostic Considerations

• The diagnosis of chorea can be challenging, with many patients remaining undiagnosed 5
• Diagnostic workup should focus on identifying the underlying cause, as many disorders presenting with chorea are potentially treatable 6
• Genetic testing is the diagnostic test of choice for suspected Huntington's disease and should be performed in concert with initial imaging 1
• In cases of suspected Wilson's disease, MRI should be considered prior to treatment in all patients with neurologic manifestations 3

Clinical Implications

• While chorea itself is a symptom rather than a disease, recognizing the correct etiology is critical, as numerous disorders in this category are potentially curable or treatable with early intervention 2
• Treatment approaches are predominantly symptomatic for many choreiform disorders, with a focus on multidisciplinary care 7
• In cases where chorea occurs during treatment of neuropsychiatric conditions, it can be difficult to distinguish between medication side effects (tardive dyskinesia) and the development of a neurodegenerative disease 7

In summary, the evidence strongly supports that chorea results from damage to or dysfunction of the basal ganglia, with different etiologies affecting these structures through various pathophysiological mechanisms.