Paroxysmal exercise-induced dystonia due to GLUT1 mutation can be responsive to levodopa: a case report

Abstract

Dear Sirs,Paroxysmal exercise-induced dyskinesia (PED) is a disor-der characterized by brief episodes of dystonia or choreausually lasting a few minutes [1]. Invariably, the movementdisorder affects the part of the body which is exercised.Less than 30 % of PED cases are due to a mutation in theSLC2A1 gene encoding for the glucose transporter type 1(GLUT1) [2–4]. This disorder is difficult to treat, and anumber of drugs have been proven unhelpful [5]. Recently,ketogenic diet has been suggested to be useful [6]. How-ever, such diet is difficult to follow and long-term com-pliance is poor [6]; also, it has been reported to worsen theattacks in some patients [7]. Hence, there is a need for othersymptomatic treatments. Here we report a case of PEDassociated with a GLUT1 mutation where the patientresponded dramatically to levodopa.This 47-year-old gentleman, with no family history forany neurological disorder, developed his first symptomsduring childhood, with dystonic attacks affecting mainlyhis legs after physical exercise. The attacks lasted20–165 min and occurred daily on average. He had nofurther symptoms in between attacks. The neurologicalexamination was normal interictally. A number of inves-tigations, including routine blood tests, brain CT scan andMRI, and dopamine transporter SPECT were normal.Cerebrospinal fluid to blood glucose ratio was consistentwith GLUT1 deficiency (ratio = 0.45; normal values[0.60 [2, 3]). He was therefore tested and found positivefor a previously reported mutation (p.R333Q) in theSLC2A1 gene.Our patient refused treatment with ketogenic diet (whichshould be considered the first-line option [5]) and preferredto try pharmacological approaches. Trials with oxazepam,diazepam, carbamazepine, clonazepam, sodium valproate,and acetazolamide were completely unhelpful. Finally, weempirically treated him with levodopa to reach a dose of800 mg daily. Since being on this dose of levodopa, hemarkedly improved, with a reduction of both frequency andintensity of the attacks. At some stage, he spontaneouslyreduced the levodopa to 200 mg daily, making his condi-tion much worse with frequent and severe episodes.Therefore, he went back to 800 mg daily; since then, he hashad only one minor episode over 6 months.Pathophysiological underpinnings of PED are not yetestablished. However, there are some suggestions thatdopamine can be involved in the pathogenesis of PED.Firstly, from a phenomenological perspective, dyskinesiasassociated with GLUT1 affect the legs and somehowresemble diphasic dyskinesias of Parkinson’s disease(which are usually seen during low dopaminergic states)and respond to high dose of levodopa, unlike what happenswith peak dose dyskinesias. Secondly, CSF analysis ofpterins and monoamine metabolites before and after anattack in a patient with PED has given evidence that theremight be an altered dopaminergic transmission whichcontributes to the clinical appearance of the abnormal