Efficacy of intravenous immunoglobulin for treatment of Lambert-Eaton myasthenic syndrome without anti-presynaptic P/Q-type voltage-gated calcium channel antibodies: a case report.

We evaluated the efficacy of intravenous immunoglobulin (IVIg) in a patient with Lambert-Eaton myasthenic syndrome (LEMS). Comprehensive clinical and electrophysiological testing was performed on a 34-year-old woman with progressive limb weakness, before and after IVIg treatment. Neurological examination revealed muscle weakness, predominantly in the proximal parts of the limbs. Muscle weakness improved following a short period of maximum voluntary muscle contraction. A repetitive low-rate (3-Hz) nerve stimulation test of the abductor hallucis was normal, but high-rate (20-Hz) stimulation induced an incremental response. Anti-presynaptic P/Q-type voltage-gated calcium channel (P/Q-VGCC) antibodies were absent in the patient's serum. Whole body computed tomography revealed no tumors. We diagnosed seronegative LEMS without tumor and treated the patient with IVIg. Both clinical and electrophysiological indices improved gradually after treatment. This case study indicates that treatment with IVIg is equally effective for LEMS that is seronegative or seropositive for P/Q-VGCC antibodies.

Intrathecal injection of P/Q type voltage-gated calcium channel antibodies from paraneoplastic cerebellar degeneration cause ataxia in mice.

The role of antibodies against the P/Q type voltage-gated calcium channels (VGCC-ab) in the pathogenesis of paraneoplastic cerebellar degeneration (PCD) and lung cancer is unclear. We evaluated in mice the effect of intrathecal injection of IgG purified from serum of a patient with both PCD and Lambert-Eaton myasthenic syndrome (LEMS), and from another patient with isolated LEMS. Mice injected with PCD/LEMS IgG developed marked, reversible ataxia compared with those injected with LEMS or control IgG. These findings suggest that P/Q-type VGCC-ab may play a role in the pathogenesis of ataxia in patients with PCD and SCLC.

Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome.

We investigated coexisting autoantibodies in sera of 553 patients with a neurological presentation and one or more paraneoplastic neuronal nuclear or cytoplasmic autoantibodies: antineuronal nuclear autoantibody type 1 (ANNA-1), ANNA-2, ANNA-3; Purkinje cell cytoplasmic autoantibody type 1 (PCA-1), PCA-2; and CRMP-5-immunoglobulin G or amphiphysin-immunoglobulin G. Except for PCA-1, which occurred alone, 31% of sera had more than one of these autoantibodies. In addition, 25% of sera had neuronal calcium channel (P/Q-type or N-type), potassium channel, ganglionic acetylcholine receptor, muscle acetylcholine receptor, or striational antibodies. The autoantibody profiles observed in patients with paraneoplastic disorders imply the targeting of multiple onconeural antigens and predict the patient's neoplasm, but not a specific neurological syndrome.