Paraneoplastic neurologic syndrome (PNS)

Paraneoplastic neurologic syndrome (PNS) represents the remote effects of cancer on the nervous system. Such syndromes can affect any part of the nervous system the neuromuscular junction, and muscle. In most patients, the neurological disorder develops before the first sign of a tumor and the patient is referred to the neurologist who has the charge of identifying a neurological disorder as paraneoplastic.

Paraneoplastic neurologic syndrome usually lead to detection of the cancer. They can be isolated or occur in association. Survival is usually influenced by the cancer, but PNS can cause severe disability and may be fatal. The most common PNS are Lambert-Eaton myasthenic syndrome (LEMS), subacute cerebellar ataxia, limbic encephalitis (LE), opsoclonus-myoclonus (OM), retinopathies (cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), Stiff-Person syndrome (SPS), chronic gastrointestinal pseudoobstruction (CGP), sensory neuronopathy (SSN), encephalomyelitis (EM) and dermatomyositis.

PNS are caused by autoimmune processes triggered by the cancer and directed against antigens common to both the cancer and the nervous system, designated as onconeural antigens. Due to their high specificity (> 90%), the best way to diagnose a neurological disorder as paraneoplastic is to identify one of the well-characterized anti-onconeural protein antibodies(Hu, Yo, Ri, CV2/CRMP5, Ma2, amphiphysin, and Tr) in the patient's serum. In addition, as these antibodies are associated with a restricted range of cancers, they can guide the search for the underlying tumor at a stage when it is frequently not clinically overt. This is a critical point as, to date, the best way to stabilize PNS is to treat the cancer as soon as possible.

The therapeutic options include immunomodulatory drugs (Corticosteroids, high-dose immunoglobulins, plasma exchange and immunosuppression) and therapeutic options like Chemotherapy, surgery and radiation therapy.

Relevant Literature

1. Posner JB. Paraneoplastic syndromes. In: Posner JB, ed. Neurologic Complications of Cancer. Philadelphia, PA: FA Davis Co; 1995:353-385

2. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349(16):1543-1554

3. Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004;75 (8):1135-1140

4. Vitaliani R, Mason W, Ances B, Zwerdling T, Jiang Z, Dalmau J. Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol. 2005;58(4):594-604

Relevant links

Goodpasture epitope