N -acetylcysteine and Unverricht–Lundborg disease Variable response and possible side effects

Abstract

Serum glutathione levels were assessed in a patient with genetically proven Unverricht-Lundborg disease (ULD) before and during treatment with the antioxidant N-acetylcysteine (NAC). Glutathione levels were low before treatment, and increased during treatment. This increase was mirrored by an improvement in seizures, but not in myoclonus or ataxia. Three other patients with clinically determined ULD showed a variable response and some notable side effects during treatment with NAC.

Tolerability and Safety of Combined Glatiramer Acetate and N-Acetylcysteine in Relapsing-Remitting Multiple Sclerosis

“…One patient with ULD developed reversible neutropenia after treatment with NAC 6 g/d for 11 months. 12 In the present investigation, no adverse hematological effects were observed.…”

“…12 However, this AE has not been reported in other trials involving long-term NAC exposure: 4 patients with ULD treated with 4 to 6 g/d for up to 30 months, 21 ; patient with ULD treated with 6 g/d for 10 months 32 ; 4 patients with ULD and 1 patient with Lafora body disease treated with 6 g/d of NAC for 3 to 60 months. 33 Monitoring of hearing function revealed no deficits in the current study.…”

“…Vital signs, hearing function, 12 and AEs were assessed at baseline, before the first dose of NAC, and at every subsequent visit. Laboratory tests (serum chemistry, hematology, urinalysis) were performed at weeks 0, 4, 16, and 36.…”

“…A study of 4 patients with UnverrichtLundborg disease (ULD) treated with oral NAC 3 to 6 g/d for up to 12 months provides additional long-term safety information. 12 Nausea and epigastric pain occurred in one patient. Another patient developed sensorineural deafness 5 weeks after starting NAC at a dose of 3 g/d.…”

Treatment options for epileptic myoclonus and epilepsy syndromes associated with myoclonus

“…At present, brivaracetam, a drug chemically related to LEV, has been granted an orphan drug status for the treatment of myoclonus, and results of a recent Phase III trial of this drug in patients with ULD should be available soon. N-acetylcysteine has been shown to induce dramatic improvement in tremor, gait and myoclonus [13], but a recent study pointed to variable responses and sensorineural deafness as a side-effect of this medication [14]. In a study with five ULD patients, lamotrigine was not effective in two cases of advanced disease, and it increased the myoclonus in three patients (dose-dependent increases in 2 of them) [15].…”