PYRUVATE DEHYDROGENASE DEFICIENCY, DYSTONIA AND DEEP BRAIN STIMULATION

Purpose: Pyruvate dehydrogenase deficiency (PDH) is an X-linked inherited neurodegenerative mitochondrial disorder with diverse neurological manifestations, including secondary dystonia. We present the unique case of a 10 year old female with PDH-related dystonia and bilateral globus pallidus internus (GPi) necrosis who successfully underwent subthalamic nucleus (STN) deep brain stimulation (DBS). Methods: This is the case of a 10 year old right-handed female who was referred to neurology at Cook Children's Hospital for progressive weakness, an abnormal brain scan, and concern for PDH. In January, 2011, at the age of 8, she presented to her pediatrician with an upper respiratory illness and weakness. She developed trouble walking and was sent to the local hospital for a neurologic evaluation. Her presenting symptoms at the time were ataxia, slurred speech and increased episodes of falling. Her MRI revealed T2 signal hyperintensity in the globus pallidus and the cerebral peduncles and dorsal mid brain in the periaqueductal region. She failed to improve over several months before genetic testing confirmed PDH. A repeat MRI showed cystic regions in the same location as the previous hyperintense signals. After failing medication, botox, and intrathecal baclofen, she underwent DBS placement on April 4, 2012 with DBS electrodes implanted into the sub-thalamic nucleus (STN) bilaterally. Results: She has regained the ability to walk with the assistance of a walker and bilateral ankle-foot orthotics (AFOs). Conclusions: This is an unusual presentation of generalized dystonia secondary to pyruvate dehydrogenase deficiency. Our patient's treatment was further complicated by the complete obliteration of the GPi, thought to be due to metabolic insult from her PDH. The overall response to STN-DBS was significant, clearly perceived by the patient and family, and has proved to be longstanding by the follow-up duration of 2 years. While GPi is the established primary target for dystonia, this case suggests that STN may become an appealing target, especially in cases with either functional or surgical pallidotomies. The significant improvement of the patient's symptoms also contributes to growing evidence that DBS may be a useful treatment in cases of secondary dystonia, including those caused by mitochondrial disorders like PDH.