Cerebrospinal fluid from multiple sclerosis patients inactivates neuronal Na+ current

Multiple sclerosis is a common inflammatory disease of the CNS. A great number of immunologically active molecules have been identified in the CSF of these patients (CSF-MS), but the role of these substances in neuronal dysfunction, especially in the origin of transient symptoms, is unclear. Therefore, we investigated the effect of CSF from 13 multiple sclerosis patients on membrane currents of cultured cortical neurons from embryonic rat and compared it with the effect of CSF from 12 patients with non-inflammatory neurological diseases. We found an increase in Na+ current (INa) inactivation by a shift of the hoo curve to more hyperpolarizing potentials by 9.3 mV. This effect was reversible by washing and could be abolished by CSF-MS heat inactivation. The degree of the shift ranged from 4.3 mV to 17.6 mV and correlated with the IgG index, but not with the degree of pleocytosis, protein or albumin content. The maximal amplitude of INa was unchanged. We concluded that diffusible factors are released into the CSF which reduce neuronal excitability and thereby disturb the function of the neuronal network. These factors may well contribute to transient neurological symptoms seen in patients with "active' multiple sclerosis.