Anti-Hu antibody syndrome is a paraneoplastic neurological disorder strongly linked with small cell lung cancer (SCLC). It occurs when the immune system produces anti-Hu antibodies that cross-react with neuron-specific RNA-binding proteins → leading to widespread neuronal injury. ⚠️ It belongs to the spectrum of paraneoplastic syndromes, where immune responses to cancer damage the nervous system rather than the tumour itself.

🎯 Associated Cancer

💨 Primary Association: Small cell lung cancer (SCLC).
Less common: neuroblastoma (in children), prostate or breast cancers.

🧩 Clinical Presentation

Symptoms depend on the nervous system regions affected:

🌉 Paraneoplastic Brain Stem Encephalitis: Dysphagia, dysarthria, facial weakness, diplopia, abnormal eye movements.
🎯 Cerebellar Degeneration: Progressive gait ataxia, dysmetria, tremor, loss of coordination.
🦶 Sensory Neuronopathy / Sensory Ataxia: Loss of proprioception, imbalance, pseudoathetosis.
🛌 Often subacute and relentlessly progressive; symptoms may precede cancer diagnosis by months.

🔎 Investigations

Diagnosis relies on both antibody testing and exclusion of other causes:

🧪 Anti-Hu Antibody: Serum or CSF positivity = diagnostic hallmark.
🧠 MRI Brain/Spine: Often normal; may show non-specific signal changes.
💉 CSF Analysis: Mild lymphocytic pleocytosis, raised protein, oligoclonal bands.
📈 Paraneoplastic screen + CT chest/abdomen or PET scan to detect underlying tumour.

💊 Management

Therapy is often difficult and response is limited:

🛡️ Immunosuppression: High-dose corticosteroids, IVIg, or plasma exchange (variable benefit).
💉 Other agents: Rituximab, cyclophosphamide, tacrolimus sometimes trialled.
🎗️ Oncological Treatment: Treating SCLC (chemotherapy, radiotherapy) may stabilise or modestly improve neurological symptoms.
🧑‍⚕️ Supportive care: Physio, OT, speech and swallow therapy, palliative input.

📉 Prognosis

Overall prognosis is poor. ⏳ Neurological deficits are usually permanent and progressive. 🔑 Early cancer treatment may prolong survival but reversal of neurological symptoms is rare.

💡 Exam Pearls

Anti-Hu = SCLC + sensory neuronopathy ± encephalitis.
Differentiate from other paraneoplastic syndromes: – Anti-Yo: cerebellar degeneration in breast/ovarian Ca. – Anti-Ri: opsoclonus-myoclonus in breast/SCLC.
Always investigate for occult malignancy when Anti-Hu antibodies are detected.

📚 References

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Anti-Hu antibodies