Paraneoplastic neurologic syndromes associated with raised anti-Hu antibody levels

Paraneoplastic neurologic syndromes (PNS) are disorders associated with cancer but without a direct effect of the tumour mass or its metastases on the nervous system

• PNS are rare and affect less than 1% of patients with cancer
  • paraneoplastic encephalomyelitis (PEM) and paraneoplastic sensory neuronopathy (PSN) are clinically well-defined, frequently overlapping, and almost always associated with anti-Hu antibodies and small-cell lung cancer (1)
  • PEM/PSN syndrome is characterized by a high titer of anti-Hu IgG antibodies in the serum and cerebrospinal fluid (CSF), the presence of inflammatory infiltrates of T cells and B cells in the nervous system, and the existence of a tumor, generally small-cell lung cancer
    • thus anti-Hu antibody is considered to be a marker for PEM and PSN, especially in association with small-cell lung carcinoma
      • nearly 80% of neoplasms associated with PEM/PSN are small-cell lung cancer
        • theorised that the immune response becomes misdirected to neurons that also express Hu antigens
      • this immune response may inhibit cancer growth as patients with anti-Hu antibodies tend to have smaller, more restricted tumors, that occasionally can regress spontaneously (3)
      • an aggressive search for malignancy is required to identify the occult cancer in most cases (4).

Reference:

1. Fujimoto S et al. A clinicopathological study of a patient with anti-Hu-associated paraneoplastic sensory neuronopathy with multiple cranial nerve palsies. Clin Neurol Neurosurg. 2002 May;104(2):98-102.
2. Dalmau et al. Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer—a quantitative Western blot analysis, Ann Neurol 1990;27: 544–552
3. Gill S et al. Paraneoplastic sensory neuronopathy and spontaneous regression of small cell lung cancer, Can J Neurol Sci 2003;30:269–271.
4. Lucchinetti CF et al. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology 1998; 50: 652–657.