Positive symptoms in multiple sclerosis: their treatment with sodium channel blockers, lidocaine and mexiletine.
Patients with multiple sclerosis (MS) often show positive symptoms of painful tonic seizure and dysesthesia as well as negative symptoms of paralysis and hypesthesia. Positive manifestation is paroxysmal and/or persistent. These are considered to be mediated by ectopic impulses generated at the site of demyelination, whereas negative symptoms are caused by conduction block. Conduction block at a demyelinated segment should reduce positive symptoms, but worsen negative ones. As reported previously, lidocaine, an Na channel blocker unmasks silent negative symptoms presumably by further reducing the action current in demyelinated portions and blocking conduction. Furthermore, because it blocks Na channels in a voltage- and frequency dependent manner, fibers that mediate positive symptoms are preferentially blocked. We administered lidocaine to 30 MS patients with positive symptoms. Lidocaine (mean plasma level, 2.4 pg/ml) almost completely abolished the paroxysmal manifestation of painful tonic seizures, neuralgic attacks, paroxysmal itching, and Lhermitte's sign. It also markedly alleviated persistent symptoms, but less so than paroxysmal symptoms. Similar effects were obtained with orally-administered mexiletine (300-400 mg/day), a derivative of lidocaine, but to a lesser extent. Na channel blockers have a dual effect on symptoms in MS, depending on whether symptoms are positive or negative. The mechanism that produces positive symptoms and the effects of the drugs on these symptoms are discussed.
Sakurai
M
M
Department of Neurology, Graduate School of Medicine, University of Tokyo, Japan. sakuraim-neu@h.u-tokyo.ac.jp
Kanazawa
I
I
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000627:therapeutic use*; D008297:Male; D008801:Mexiletine / Q000627:therapeutic use*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D026941:Sodium Channel Blockers
D026941:Sodium Channel Blockers; D008801:Mexiletine; D008012:Lidocaine