Studies on pathophysiology and effects of botulinumtoxin in focal dystonia

Sammanfattning: The pathophysiology of focal dystonia, such as cervical dystonia (CD) and writer's cramp (WR) isfar from determined and the development of effective treatment is thus impeded. The dystonia in WRis often action-specific , and most dystonic patients experience an action-induced worsening of thesymptoms. Patients with CD and WR were studied at rest and during activity by differentneurophysiological methods Intramuscular botulinumtoxin (BTX) injection are increasing1y utilizedin the treament of the focal dystonias. The effects of BTX in CD paients were studied withelectromyography (EMG) and with measurements of clinical efficacy. Bursts of involuntary activity were recorded with EMG in CD patients' sternocleidomastoidmuscles (SCMs), both at rest and during a slight muscle contraction Transcranial magneticstimulation (TMS) induced motor evoked potentials (MEPs) with abnormally short latencies in theSCMs of CD patients. The onset of TMS induced suppression of EMG activity occurred abnormallylate in the CD patients' SCMs. The CD patients' clinical signs were compatible with a unilateralcentral dysfunction, whereas the abnormal results of TMS were seen bilterally both at rest andduring SCM contraction. Studies of precision grip function in patients with WR showed impairedabilities to coordinate grip and lift force trajectories, and to correct erroneously programmed gripforce according to sensory feedback. The WR patients further ha abnormally large grip forceincreases in response to a sudden load increase. The findings in the EMG, TMS and precision gripstudies suggest an impaired motor control in dystonia due to increased motoneuronal excitability anddeficiencies of inhibitory regulation. Dystonic signs increased, and positron emissioon tomographyshowed increased regional cerebral blood flow (rCBF) in the left primary sensory-motor and premotorcortical areas, the left thalamus and the right cerebellum, as WR paients wrote for longer periodsThese rCBF increases suggest an increased activation of a cerebro.cerebellar motor circuit indystonia. The WR patients concurrently prosgressively decreased the rCBF in the left supramarginaland angular gyri. Control subjects had no progressive changes of rCBF during prolonged writing, buttheir rCBF changes during writing(compared to during drawing) resembled the WR patients' patternof progressive rCBF changes during prolonged writing. The normal cerebral processes during writinseem thus to be exaggerated in WR, wich may contribute to the task-specific dysfunction. Data from CD status scales according to Tsui and to Fahn correlated well with pathient'ratingof the BTX treament effect. BTX injections improved but failed to nomalize CD patients' qualityof life. EMG of single motor units in SCMs repeatedly injected with BTX indicated persitentreduction of the number of size of functional muscle fibres, but otherwise restored functionalneuromuscular organization when CD symptoms had relapsed. Keyword: Dystonia, cervical dystonia, writer's cramp, pathophysiology, botulinumtoxin electromyography, transcranial magnetic stimulation, precision grip, motor control, positron emission tomography, regional cerebral blood flow, quality of life.