24A. Paraneoplastic nervous system diseases

Page created on June 3, 2021. Last updated on June 3, 2022 at 08:32

Definition and epidemiology

Paraneoplastic nervous system diseases occur in 1 – 3% of patients with cancer. They often develop before the cancer diagnosis. They usually occur because the tumour expresses antigens which are structurally similar to antigens on neurons (molecular mimicry). Antineuronal antibodies are often present in the serum and CSF.

It’s important to recognise these diseases because they can give earlier diagnosis of the tumour and because their prognosis is better the earlier the treatment is initiated. These conditions are usually treated by steroids and plasma exchange.

The most common underlying cancers are:

  • Neuroendocrine tumours
    • Small cell lung cancer
    • Ovarian cancer
    • Prostate cancer
  • Breast cancer
  • Lymphoma

We can classify them according to whether they’re associated with antibodies against neuronal surface antigens or nuclear antigens:

  • Neuronal nuclear antibody-associated types
    • Antibodies against nuclear antigens
    • Respond poorly to therapy
    • Specific types
      • Paraneoplastic cerebellar degeneration
      • Paraneoplastic sensory neuronopathy
      • Limbic encephalitis caused by anti-Ma2
  • Neuronal surface antibody-associated types
    • Antibodies against surface antigens
    • Respond better to therapy, especially plasma exchange
    • Not all are paraneoplastic, can be autoimmune as well
    • Specific types
      • Anti-NMDA receptor encephalitis
      • Limbic encephalitis caused by other antibodies

Many of the paraneoplastic encephalitides are limbic encephalitides, i.e., affecting the limbic system in the medial temporal lobe. Limbic encephalitis usually causes neuropsychiatric symptoms and seizures.

Anti-NMDA receptor encephalitis

This is a type of limbic and striatal encephalitis which is caused by antibodies against the NMDA receptor. There is almost always an underlying ovarian teratoma or another malignancy. It mostly affects young women and is rare, affecting only 1,5 per million per year.

Anti-NMDA receptor encephalitis causes both psychiatric and neurological symptoms. Psychiatric symptoms include psychosis, agitation, etc. Neurological symptoms include dyskinesia, memory problems, and seizures.

Anti-NMDA receptor antibodies are present in both serum and CSF. All patients should be screened for underlying malignancy.

It has a good response to immunotherapy (glucocorticoids/IVIG/plasma exchange) and removal of the tumor.

Anti-Ma2 encephalitis

Anti-Ma2 encephalitis is another cause of limbic encephalitis. There is often an underlying testicular cancer. It presents with memory deficits, seizures, and irritability. It has a poor response to therapy.

Paraneoplastic sensory neuronopathy

This is a severe neuronopathy (degeneration of dorsal root ganglia neurons) with only sensory symptoms, characterised by asymmetric paraesthesia and severe pain of the upper limbs. It has a poor response to therapy.

Paraneoplastic cerebellar degeneration

This is a subacute cause of cerebellar degeneration, which presents with cerebellar symptoms. It has a poor response to therapy.


Dermatomyositis can be paraneoplastic as well. Described in topic 1A.

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