Paraneoplastic nervous system syndromes

Paraneoplastic Nervous System Syndromes of the Neuromuscular Junction 

Myasthenia gravis, LEMS, and neuromyotonia affect the neuromuscular junction. These disorders are not necessarily associated with malignancy but are sometimes associated with tumors and are regarded as PNS in these patients. 

Neuromyotonia, or Isaacs syndrome, can occur as a paraneoplastic manifestation [138]. In a study of 60 patients with neuromyotonia, 8 individuals developed lung cancer or malignant lymphoma [139]. Importantly, and in contrast to most other PNS, the tumors presented after the symptoms of nerve hyperexitability, in some cases up to 4 years later. This long latency has also been reported in LEMS with SCLC [140]. 

VGKC antibodies can be present in paraneoplastic neuromyotonia. However, VGKC antibodies are probably much more common in nonpara-neoplastic disease (nonparaneoplastic LE, neuromyotonia, and Morvan s syndrome) [51, 139, 141]. 

The diagnostic considerations in PNS are complex and hardly straightforward. Problematic issues include antibody positivity vs negativity, patients with no detectable tumor and the ongoing characterization of new syndromes as well as new antibody specificities. Guidelines of the diagnostic criteria of PNS have been established by an international network of 

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

Fumeaux HF, Reich L, Posner JB. Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 1990 40(7) 1085-1091. 

Current opinions on cause and mechanism include the possibility that MS is often due to a form of molecular mimicry, in which an immune response to an infective or other exogenous agent leads to the formation of antibodies and/or cells that cross-react destructively with components of normal myelin. Molecular mimicry is well established in certain other disorders of the nervous system (Candler et al., 2006) including paraneoplastic syndromes (Posner, 2003). 

Vecht CJ, Moll JWB, Henzen-Logmans SC (1991) Paraneoplastic syndromes of the central nervous system. The Cancer Journal. 4, 357-363. 

The paraneoplastic syndromes of the nervous system arise in association with a cancer (Darnell Posner, 2003). However, the neurological symptoms are characteristic of certain types of cancer and often precede the identification of the underlying malignancy. Therefore, proper identification of the neurological disorder will be of help in finding the cancer that causes the neurological disability. Most of these disorders are immune-mediated and characterized by the presence of autoantibodies. Sensory neuropathy and limbic... 

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