When Multiple System Atrophy Masquerades as CASPR2 Autoimmune Encephalopathy: A Diagnostic Pitfall

Jun Zhang¹ming yue wang²le chen²jun li^2*

• ¹Xuanwu Hospital, Capital Medical University, Beijing, China
• ²Beijing Tsinghua Changgung Hospital, Beijing, China

Introduction: Multiple system atrophy (MSA) is a sporadic, adult-onset neurodegenerative disorder characterized by rapid progression. Early diagnosis remains particularly challenging, especially when CASPR2 antibodies are detected during the early stages of disease progression. Case presentation: A 56-year-old female presented with chronic progressive cerebellar ataxia. Serum analysis revealed the presence of CASPR2 antibodies. Brain MRI demonstrated atrophy of the brainstem and cerebellum. The external anal-sphincter electromyography (EAS-EMG) indicated autonomic nerve dysfunction in the absence of overt clinical symptoms. Despite treatment with high-dose corticosteroids and immunosuppressants, no clinical improvement was observed. During follow-up, symptoms of autonomic nerve dysfunction emerged, leading to a clinical established diagnosis of cerebellar subtype of multiple system atrophy (MSA-C). Conclusion: In the early stages of MSA, autonomic nerve dysfunction may not manifest clinically. Therefore, close follow-up is essential for accurate diagnosis. EAS-EMG exhibits high sensitivity in detecting subclinical autonomic dysfunction. Although the co-occurrence of MSA-C and high-titer (1:100) CASPR2-IgG is uncommon, this case highlights the critical importance of relying on the overall clinical presentation, rather than on isolated laboratory findings, to establish the primary diagnosis.Additionally, CASPR2 antibodies can occur in other neurological conditions; thus, caution is warranted when diagnosed CASPR2-associated disease with low-titer CASPR2 antibody.