Effect of Botulinum Toxin on Non-Motor Symptoms in Cervical Dystonia

Abstract

Patients with cervical dystonia (CD) may display non-motor symptoms, including psychiatric disturbances, pain, and sleep disorders. Intramuscular injection of botulinum toxin type A (BoNT-A) is the most efficacious treatment for motor symptoms in CD, but little is known about its effects on non-motor manifestations. The aim of the present study was to longitudinally assess BoNT-A’s effects on CD non-motor symptoms and to investigate the relationship between BoNT-A-induced motor and non-motor changes. Forty-five patients with CD participated in the study. Patients underwent a clinical assessment that included the administration of standardized clinical scales assessing dystonic symptoms, psychiatric disturbances, pain, sleep disturbances, and disability. Clinical assessment was performed before and one and three months after BoNT-A injection. BoNT-A induced a significant improvement in dystonic symptoms, as well as in psychiatric disturbances, pain, and disability. Conversely, sleep disorders were unaffected by BoNT-A treatment. Motor and non-motor BoNT-A-induced changes showed a similar time course, but motor improvement did not correlate with non-motor changes after BoNT-A. Non-motor symptom changes after BoNT-A treatment are a complex phenomenon and are at least partially independent from motor symptom improvement.

Potential Interactions Between Cerebellar Dysfunction and Sleep Disturbances in Dystonia

“…As cervical dystonia is associated with abnormally increased cerebellar connectivity with the sensorimotor cortex (5), the improvement of motor symptoms following the decrease in cerebellar connectivity after BoNT injections may be expected. Such an improvement is not seen in sleep disruption (52), which remains after repeated treatment. These data argue that although cerebellar overactivity could contribute to circadian dysfunction in dystonia, the pathways affected by BoNT are functionally and anatomically distinct from those involved in sleep, which is perhaps not unexpected, given that the BoNT injections are given at the focal peripheral sites where dystonia is manifest rather than as a systemic administration typical of oral or other parenteral forms of drug administration.…”

“…is challenging. Moreover, stress and anxiety, which are known to have unique relationships with sleep and the circadian system (150), are notable non-motor symptoms in dystonia that are typically unaddressed by common and often effective treatments like BoNT therapy (46,52). Another question to resolve emerged with the existence of mixed evidence regarding the prevalence of sleep disorders in dystonia; a study of 24 patients with both primary and secondary dystonia showed similar sleep organization and architecture relative to controls (151).…”

“…Nevertheless, it is becoming increasingly apparent that sleep disturbances are not only common among those affected by motor disorders (13,46,51,52,59,60,61,62,135,136,152), but that these disturbances are more than secondary symptoms. If we are to deeply and better understand network disorders like dystonia, we must approach future investigations into the mechanisms and potential therapies of the condition with a mindset that places the non-motor complications, such as sleep, in the same hierarchy as the visible motor complications that remain at the forefront of investigation.…”

“…While some patients do experience improvements in depression following BoNT treatment targeting motor symptoms (49), others see little improvement, failing to see any causative relationship between motor symptom severity and non-motor symptoms (50). Impaired sleep, in particular, appears to be unaffected by BoNT therapy (51,52). These results are in line with research delineating the role of the cerebellum in regulating non-motor behaviors (53)(54)(55)(56), suggesting that the non-motor symptoms are a result of aberrant cerebellar activity in dystonia, rather than a result of the ultimate motor deficits generated by a canonical network.…”

Effects of Botulinum Toxin Therapy on Health-Related Quality of Life Evaluated by the Oromandibular Dystonia Rating Scale

“…Unfortunately, the number of participants was relatively low, and differences in OMD subtypes were not considered; thus, the reliability remains uncertain. Apart from motor phenomena, there are other non-motor symptoms such as depression, anxiety, sleep problems, and pain in many patients with dystonia [ 28 , 29 , 30 , 31 , 32 ]. Non-motor symptoms are increasingly recognized as important determinants of HRQoL in cervical dystonia [ 29 , 30 , 31 , 32 ].…”