Intrathecal Baclofen As an Effective Antidystonic Treatment Option in Patients with ARX-mutation: A Case Report

Introduction: Mutations in the X-chromosomal ARX (Aristaless-related homeobox)—gene cause epilepsy, genital malformations, mental retardation, structural brain malformations, and also dystonia. Dystonia in patients with ARX mutations is often severe, may be difficult to distinguish from epileptic seizures and significantly impairs the patients’ daily activities and quality of life. We report our experience with intrathecal Baclofen as an antidystonic therapeutic approach in a patient with ARX mutation.

Patient: Dystonia in the 6-year-old patient with a de novo mutation in the ARX gene (c.315_335dup;p.Ala109_Ala115dup) developed at the age of 3 months and severely affected the patient’s daily activities. Furthermore, one episode of dystonic storm with rhabdomyolysis was reported. Oral antidystonic drugs showed no satisfactory effects (baclofen orally, l-Dopa) or even caused deterioration (tetrabenazine). Because of the severity of the symptoms, the patient was chosen as a candidate for intrathecal baclofen therapy (ITB), as ITB had previously been proven effective in another patient with ARX-associated dystonia (Dr. G. Wohlrab, MD, personal oral communication).

Methods: Individual goals of everyday life were defined via Goal Attainment Scale (GAS). An extensive analysis of the dystonic movement disorder before and after surgery was performed via Barry Albright Dystonia Score (BAS) and video documentation. To evaluate the health-related quality of life, the CPCHILD questionnaire (Available at: http://www.sickkids.ca/Research/CPCHILD-Questionaire/CPCHILD-Project/index.html) was used before and after the start of ITB.

Results: The patient responded very well even to a relatively low dose of 150 µg baclofen i.t./d (Medtronic Synchromed II, 20 mL, Simple Continuous Mode); the dystonic movement disorder improved considerably. While the BAS was still unchanged 3 weeks after surgery (28/28 points), CPCHILD showed significant improvement of the health-related quality of life (total score preoperative 18/100, postoperative 49/100). In the GAS, expectations were met (1/4), respectively exceeded (3/4) in all four items.

Discussion: Intrathecal Baclofen was an effective antidystonic treatment option in our patient with ARX-mutation which led to significant—and objectively measurable—improvement of the patient’s quality of life. In summary, ITB has now been successfully applied in two patients with ARX-associated dystonia.