Authors :
Presenting Author: Takeshi Suzuki, MD, PhD – Okazaki City Hospital
Jun Natsume, MD, PhD – Department of Pediatrics – Nagoya University Graduate School of Medicine; Yuji Ito, MD, PhD – Department of Pediatrics – Nagoya University Graduate School of Medicine; Tadashi Ito, PT, PhD – Three-dimensional motion analysis room – Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities; Koji Noritake, MD, PhD – Department of Orthopedic Surgery – Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities; Fumie Kinoshita, PhD – Department of Advanced Medicine – Nagoya University Hospital; Tatsuya Fukasawa, MD – Department of Pediatrics – Anjo Kosei Hospital; Takeshi Tsuji, MD, PhD – Department of Pediatrics – Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities; Kazuya Itomi, MD, PhD – Department of Neurology – Aichi Children's Health and Medical Center; Hirokazu Kurahashi, MD, PhD – Department of Pediatrics – Aichi Medical University; Kazuo Kubota, MD, PhD – Department of Pediatrics – Gifu University Graduate School of Medicine; Tohru Okanishi, MD, PhD – Division of Child Neurology, Institute of Neurological Sciences – Tottori University School of Medicine; Shinji Saitoh, MD, PhD – Department of Pediatrics and Neonatology – Nagoya City University Graduate School of Medical Sciences; Hideshi Sugiura, MD, PhD – Department of Physical Therapy – Nagoya University Graduate School of Medicine; Hirohisa Watanabe, MD, PhD – Department of Neurology – Fujita Health University School of Medicine; Yoshiyuki Takahashi, MD, PhD – Department of Pediatrics – Nagoya University Graduate School of Medicine; Hiroyuki Kidokoro, MD, PhD – Department of Pediatrics – Nagoya University Graduate School of Medicine
Rationale:
Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy characterized by the onset of febrile or afebrile, often prolonged seizures in the first year of life, followed by multiple type seizures and slowing of developmental and cognitive skills. Gait disturbance is one of the important problems in adolescent and adult patients. No quantitative studies have been conducted to evaluate the effectiveness of medication on the gait disturbance. The aim of this study was to evaluate the effectiveness of levodopa on pathological gait in DS by three-dimensional gait analysis (3DGA).Methods:
We studied 3DGA in 14 patients with DS ranged from six to 23 years (median age, 19 years) and 14 healthy controls. We compared parameters of 3DGA between patients and controls. Nine of 14 patients with DS participated in the crossover study of levodopa and were randomly assigned to levodopa precedence group or no-levodopa precedence group. Levodopa-carbidopa hydrate was prescribed with 5mg/kg/day or 300mg/day (body weight ≥60kg). Duration of medication was four to six and wash out period was set to four weeks. 3DGA was performed three times, before the study, with levodopa and without levodopa. Mixed effect model was applied to evaluate the effectiveness of levodopa. The primary outcome was change of Gait Deviation Index (GDI) by levodopa. Spatiotemporal gait parameters, 6-minute walking distance (6MD), and balance test using stabilometry were also evaluated. It was determined if there were correlations between age or gait performance before starting levodopa and the effectiveness of levodopa.
Results:
Patients with DS showed lower value of GDI and other gait parameters than healthy controls. Levodopa improved GDI (estimated difference=4.2 points, p=0.029), 6MD (estimated difference=52m, p=0.002), and balance test (estimated difference=-4.1mm, p=0.011) of patients with DS. No severe adverse events were observed except for one patient who exhibited fever and ceased taking levodopa. Effectiveness of levodopa was higher in the patients with younger age and higher gait performance before the treatment of levodopa.Conclusions:
Our crossover randomized trial showed an evidence that levodopa had a potential to improve the gait disturbance in patients with DS.Funding:
This study was conducted with the support from The Japan Foundation for Pediatric Research (Grant No 20-003). The project title was “Randomized clinical trial of L-DOPA for gait pathology in Dravet syndrome (Principal investigator: Takeshi Suzuki)." The funders had no role in the study design, data collection, analysis and interpretation of the data or preparation of the manuscript.