Secondary and Primary Dystonia

Pathophysiological Differences

Maja Kojovic; Isabel Pareés; Panagiotis Kassavetis; Francisco J. Palomar; Pablo Mir; James T. Teo; Carla Cordivari; John C. Rothwell; Kailash P. Bhatia; Mark J. Edwards


Brain. 2013;136(7):2038-2049. 

In This Article


We have demonstrated that primary and secondary dystonia do not share the same pattern of electrophysiological abnormalities. In secondary dystonia caused by structural brain lesions, the response to PAS is normal and therefore enhanced sensorimotor cortical plasticity is not required for clinical expression of dystonia. Our data also suggest that enhanced cortical plasticity does not reflect a functional change arising secondary to dystonic activity, but rather represents a specific pathophysiological trait of primary dystonia. Cerebellar function as measured by eye blink classical conditioning is not affected in secondary dystonia, indicating that functional involvement of the cerebellum is not a universal feature of dystonia. The present study however does not resolve the ongoing debate as to whether changes in cerebellar activity in primary dystonia are (i) compensatory; (ii) an epiphenomenon occurring secondary to abnormal activity elsewhere within the sensorimotor network; or (iii) are a primary part of the pathophysiology of dystonia (Teo et al., 2009; Sadnicka et al., 2012). The compensation hypothesis is based on the idea that cerebellar hyperactivity in functional brain imaging of patients with primary dystonia can compensate for abnormalities in motor cortical plasticity. It is supported to some extent by the fact that in healthy subjects alterations of cerebellar activity using transcranial direct current stimulation reduce responsiveness to a subsequent PAS protocol (Hamada et al., 2012). In primary dystonia this compensatory activity may have deleterious effects on sensitive tests of cerebellar function, such as eye-blink conditioning, even though clinical signs of cerebellar dysfunction are absent. This would fit with the present finding that since there are no abnormalities in motor cortical plasticity in secondary dystonia, there is no need for compensatory cerebellar activity, and thus eye-blink conditioning is normal. Nevertheless, the data also could fit into the alternative hypothesis that cerebellar abnormalities are an intrinsic feature of primary dystonia, since they are absent in secondary cases.

Our findings may give some insight into why the stimulation-based therapeutic interventions that are thought to interfere with motor cortex plasticity, such as repetitive TMS and deep brain stimulation, might not be as useful in patients with secondary as in primary dystonia (Andrews et al., 2010; Vidailhet et al., 2012). Further exploration of differences in pathophysiological mechanisms in different types of dystonias may have implications in selecting the most appropriate treatment among different alternatives and also for developing new therapeutic strategies.