CEREBROSPINAL-FLUID FROM MULTIPLE-SCLEROSIS PATIENTS INACTIVATES NEURONAL NA+ CURRENT

Multiple sclerosis is a common inflammatory disease of the CNS. A grea t number of immunologically active molecules have been identified in t he 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 multi ple sclerosis patients on membrane currents of cultured cortical neuro ns from embryonic rat and compared it with the effect of CSF from 12 p atients with non-inflammatory neurological diseases. We found an incre ase in Na+ current (I-Na) inactivation by a shift of the h(oo) curve t o more hyperpolarizing potentials by 9.3 mV. This effect was reversibl e by washing and could be abolished by CSF-MS heat inactivation. The d egree of the shift ranged from 4.3 mV to 17.6 mV and correlated with t he IgG index, but not with the degree of pleocytosis, protein or album in content. The maximal amplitude of I-Na was unchanged. We concluded that diffusible factors ave released into the CSF which reduce neurona l excitability and thereby disturb the function of the neuronal networ k. These factors may well contribute to transient neurological symptom s seen in patients with 'active' multiple sclerosis.