Which paraneoplastic syndrome is most characteristically associated with anti-Hu antibodies directed against neuronal nuclear antigen ANNA-1, typically in the setting of small cell lung carcinoma?

• A Cerebellar degeneration with Purkinje cell loss
• B Limbic encephalitis with hippocampal neuron loss
• C Lambert-Eaton myasthenic syndrome with P/Q calcium channel antibodies
• D Sensory neuropathy with dorsal root ganglion degeneration ✓

Explanation

Anti-Hu (ANNA-1) antibodies target HuD, an RNA-binding protein expressed in neuronal nuclei including dorsal root ganglia neurons. The classical presentation is subacute sensory neuropathy with dorsal root ganglion degeneration, though limbic encephalitis and cerebellar degeneration can also occur. Lambert-Eaton syndrome involves antibodies against voltage-gated P/Q-type calcium channels (VGCC), not ANNA-1. Anti-Yo antibodies (anti-Purkinje cell cytoplasmic antibody) cause cerebellar degeneration.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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