title: Secondary and primary dystonia: pathophysiological differences.
abstract: Primary dystonia is thought to be a disorder of the basal ganglia because the symptoms resemble those of patients who have anatomical lesions in the same regions of the brain (secondary dystonia). However, these two groups of patients respond differently to therapy suggesting differences in pathophysiological mechanisms. Pathophysiological deficits in primary dystonia are well characterized and include reduced inhibition at many levels of the motor system and increased plasticity, while emerging evidence suggests additional cerebellar deficits. We compared electrophysiological features of primary and secondary dystonia, using transcranial magnetic stimulation of motor cortex and eye blink classical conditioning paradigm, to test whether dystonia symptoms share the same underlying mechanism. Eleven patients with hemidystonia caused by basal ganglia or thalamic lesions were tested over both hemispheres, corresponding to affected and non-affected side and compared with 10 patients with primary segmental dystonia with arm involvement and 10 healthy participants of similar age. We measured resting motor threshold, active motor threshold, input/output curve, short interval intracortical inhibition and cortical silent period. Plasticity was probed using an excitatory paired associative stimulation protocol. In secondary dystonia cerebellar-dependent conditioning was measured using delayed eye blink classical conditioning paradigm and results were compared with the data of patients with primary dystonia obtained previously. We found no difference in motor thresholds, input/output curves or cortical silent period between patients with secondary and primary dystonia or healthy controls. In secondary dystonia short interval intracortical inhibition was reduced on the affected side, whereas it was normal on the non-affected side. Patients with secondary dystonia had a normal response to the plasticity protocol on both the affected and non-affected side and normal eye blink classical conditioning that was not different from healthy participants. In contrast, patients with primary dystonia showed increased cortical plasticity and reduced eye blink classical conditioning. Normal motor cortex plasticity in secondary dystonia demonstrates that abnormally enhanced cortical plasticity is not required for clinical expression of dystonia, and normal eye blink conditioning suggests an absence of functional cerebellar involvement in this form of dystonia. Reduced short interval intracortical inhibition on the side of the lesion may result from abnormal basal ganglia output or may be a consequence of maintaining an abnormal dystonic posture. Dystonia appears to be a motor symptom that can reflect different pathophysiological states triggered by a variety of insults.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, WC1N 3BG, London, UK. maja.kojovic.09@ucl.ac.uk
authors.forename: Maja
authors.initials: M
authors.lastname: Kojovic
authors.forename: Isabel
authors.initials: I
authors.lastname: Pareés
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kassavetis
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Palomar
authors.forename: Pablo
authors.initials: P
authors.lastname: Mir
authors.forename: James T
authors.initials: JT
authors.lastname: Teo
authors.forename: Carla
authors.initials: C
authors.lastname: Cordivari
authors.forename: John C
authors.initials: JC
authors.lastname: Rothwell
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Edwards
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001767:Blinking / Q000502:physiology*; D001930:Brain Injuries / Q000150:complications; D016022:Case-Control Studies; D003214:Conditioning, Classical; D004421:Dystonia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D020821:Dystonic Disorders / Q000473:pathology / Q000503:physiopathology*; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D011712:Pyramidal Tracts / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
keywords: brain plasticity; cerebellum; dystonia; sensorimotor cortex; transcranial magnetic stimulation