Treatment options in paraneoplastic disorders of the peripheral nervous system.

OPINION STATEMENT: Paraneoplastic disorders of the peripheral nervous system (PNS) are the most frequent manifestation of paraneoplasia. As with the central nervous system, two categories of immune mechanisms are distinguished. On one side, antibodies toward intracellular antigens (HuD and CV2-CRMP5) occur with subacute sensory neuronopathy or sensorimotor neuropathy probably depending on a T cell mediated disorder (group 1). On the other side, the Lambert-Eaton myasthenic syndrome (LEMS) and peripheral nerve hyperexcitability (PNH) occur with antibodies to cell membrane antigens, respectively, the voltage gated calcium channel and CASPR2 proteins, which are responsible for the disease (group 2). Treatment recommendation mostly depends on class IV studies. Three lines of therapeutics can be proposed, namely tumor, immunomodulatory and symptomatic treatments. Cancer treatment is crucial since an early tumor cure is the best way to stabilize patients in group 1 and improve those in group 2. This implies the use of an efficient strategy for cancer diagnosis. With group 2 symptomatic treatment including 3,4 diaminopyridine for LEMS and carbamazepine for PNH may suffice to obtain good quality remission. Immunomodulatory treatments like IVIg and plasma exchange, which have a well-established efficacy in antibody dependent diseases, may be used as second line treatments. Rituximab, for which there is only little evidence in this context, may be kept in a third line for severe refractory patients. With group 1 patients, who frequently develop an evolving and disabling disorder, bolus of methylprednisolone and or IVIg may be recommended while searching for and treating the tumor. If the tumor is not found and the patient deteriorates, monthly pulses of cyclophosphamide may stabilize the patients. Antidepressants and antiepileptic drugs efficacious in the treatment of neuropathic pain are to be used as symptomatic treatment when necessary. The choice is then based on the cost effectiveness and tolerance of these drugs.