Intravenous Immunoglobulin Therapy Administered Early after Narcolepsy Type 1 Onset in Three Patients Evaluated by Clinical and Polysomnographic Follow-Up

Abstract

Narcolepsy type 1 is a rare disabling sleep disorder mainly characterized by excessive daytime sleepiness and cataplexy, an emotion-triggered sudden loss of muscle tone. Patients have a selective degeneration of hypocretin-producing neurons in the dorsolateral posterior hypothalamus with growing evidence supporting the hypothesis of an autoimmune mechanism. Few case studies that reported intravenous immunoglobulin therapy (IVIg) suggest the efficacy of IVIg when administered early after disease onset, but the results are controversial. In these retrospective case observations, IVIg cycles were initiated within one to four months after cataplexy onset in a twenty-seven-year-old man, a ten-year-old girl, and a seven-year-old boy, all three with early onset typical narcolepsy type 1. Efficacy of treatment (three IVIg cycles of 1 g/kg administered at four-week intervals) was evaluated based on clinical, polysomnographic, and multiple sleep latency test (mean latency and SOREM) follow-up. Two patients reported decreased cataplexy frequency and ameliorated daytime sleepiness, but no significant amelioration of polysomnographic parameters was observed. Given the possibility of spontaneous improvement of cataplexy frequency with self-behavioral adjustments, these observations would need to be confirmed by larger controlled studies. Based on the present study and current literature, proof of concept is still missing thus prohibiting the consideration of IVIg as an efficient treatment option.

Narcolepsy treatment: pharmacological and behavioral strategies in adults and children

“…Only a few investigators [39,[90][91][92] have tried IVIG in early-onset narcoleptic patients to understand its therapeutic efficacy, but the results are controversial due to the small sample size, openlabel design, and self-report observations. The results suggest a potential improvement in frequency and severity of cataplexy and ameliorated daytime sleepiness, data further confirmed by new evidence [93]. Given the possibility of spontaneous improvement of cataplexy [94], more controlled studies are indicated.…”

A practical guide to the pharmacological and behavioral therapy of Narcolepsy

“…To date, the results have been controversial due to the small sample size, open label design, and self-reported observations. However, an improvement in cataplexy frequency and severity, as well as in EDS, was reported, but further data are required to exclude the possibility of a spontaneous improvement in NT1 symptoms during the disease course [ 88 ]. Overall, despite some promising results, further studies should address the role of immunotherapy in NT1 [ 89 ].…”

Reviewing the Clinical Implications of Treating Narcolepsy as an Autoimmune Disorder

“…In adult cases, headache, sometimes associated with stiff neck 101 or rise in CSF leukocytes, 89 was the most common complaint, whereas one patient presented a not better-defined allergic reaction. 83 In children, side effects included infectious episodes (a flu-like syndrome and viral gastroenteritis), 78 skin reactions with urticaria and petechiae, 80 hypotension and nausea, 90 headache, fever, and flushing 70 requiring therapy withdrawal. Although until now no serious adverse events occurred in NT1 patients treated with monoclonal antibodies, these drugs have potentially lethal side effects, ie, severe infusion-related reactions, secondary autoimmunity 94 and lifethreatening infections secondary to immunosuppression, in particular progressive multifocal leukoencephalopathy (PML).…”

“… 77 In three other cases treated within 1–4 months from symptoms’ onset mixed effects were observed, with some improvement of EDS, and in two cases also of cataplexy, although no significant changes of polysomnographic parameters were documented. 78 A 16-year-old girl with NT1 and severe bizarre hallucinations, with an inflammatory CSF (positive oligoclonal bands and pleocytosis) and undetectable hcrt-1 levels at the baseline examination, was treated with IVIG and showed only a transient improvement of the hallucinations. Interestingly, the CSF pleocytosis gradually disappeared after treatment, but CFS hcrt-1 levels remained unchanged.…”

“…In adult cases, headache, sometimes associated with stiff neck 101 or rise in CSF leukocytes, 89 was the most common complaint, whereas one patient presented a not better-defined allergic reaction. 83 In children, side effects included infectious episodes (a flu-like syndrome and viral gastroenteritis), 78 skin reactions with urticaria and petechiae, 80 hypotension and nausea, 90 headache, fever, and flushing 70 requiring therapy withdrawal.…”