Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy.

BACKGROUND: Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC.

METHODS: 2 NC children received IVIG 1 g/kg/day in 2 days/month, 5 times, at 3 and 6 months disease duration, respectively. CSF and serum were analysed for hypocretin neuron autoantibodies. An association between disease duration and IVIG effect was calculated in all published NC cases.

RESULTS: Autoantibodies were not detectable. Cataplexy improved in both children but only temporarily in one patient. Subjective sleepiness temporarily improved, sleep paralysis emerged and hypnagogic hallucinations and REM sleep behaviour disorder worsened in one child. Sleep parameters and CSF hypocretin-1 remained abnormal. On a group level, IVIG treatment ≤ 9 months from disease duration predicted reduction of cataplexy (p=0.004) and sleepiness (p=0.066). Sleep parameters and CSF hypocretin-1 levels were unchanged except if treated extremely early.

CONCLUSION: IVIG treatment initiated before 9 months disease duration has some clinical efficiency. The unaffected CSF hypocretin-1 levels and lack of autoantibodies suggest that any autoimmune process occurs very early in NC. The final IVIG effect needs to be investigated in a placebo-controlled study.