Current Management in Patient with Dystonia.pptx

Management in Dystonia

1. Management in Dystonia

2. Overview Dystonia is a movement disorder characterized by sustained or intermittent abnormal movements, postures, or both. Dystonic movements and postures are typically patterned and repetitive and may be tremulous or jerky. They are often initiated or worsened by voluntary action, and frequently associated with overflow movements . Albanese, A., Bhatia, K.P., Fung, V.S.C., Hallett, M., Jankovic, J., Klein, C., Krauss, J.K., Lang, A.E., Mink, J.W., Pandey, S., Teller, J.K., Tijssen , M.A.J., Vidailhet , M. and Jinnah, H.A. (2025), Definition and Classification of Dystonia. Mov Disord , 40: 1248-1259.  https://doi.org/10.1002/mds.30220

3. Overview Region Upper Face, Lower Face, Neck, Larynx, Upper Limbs, Trunk, And Lower Limbs Albanese, A., Bhatia, K.P., Fung, V.S.C., Hallett, M., Jankovic, J., Klein, C., Krauss, J.K., Lang, A.E., Mink, J.W., Pandey, S., Teller, J.K., Tijssen , M.A.J., Vidailhet , M. and Jinnah, H.A. (2025), Definition and Classification of Dystonia. Mov Disord , 40: 1248-1259.  https://doi.org/10.1002/mds.30220 Classification Focal (only one body region is affected) Segmental ( two or three contiguous body regions are affected) Multifocal ( two or three non-contiguous body regions are affected) Hemidystonia ( unilateral involvement of the upper and the lower limbs) Generalized ( pattern of distribution that goes beyond segmental or multifocal and does not qualify for hemidystonia )

4. Management Martinez-Nunez AE, Mahajan A. Dystonia treatment: current approach and future directions. Practical Neurology (US). 2024;23(7):41-46

5. Management Martinez-Nunez AE, Mahajan A. Dystonia treatment: current approach and future directions. Practical Neurology (US). 2024;23(7):41-46

6. Levodopa Trial Any individual in the pediatric age group and any adult with focal dystonia should receive an initial treatment trial with levodopa for at least 3 month.  Levodopa should be started at a small dose of 50 mg 3 times per day and gradually increase up to a dose of 600 to 1000 mg in adults and 20 mg/kg in children. Adverse effects include primarily dyskinesia, nausea, and psychiatric disturbances Sy MAC, Fernandez HH. Dystonia and leveraging oral pharmacotherapy. J Neural Transm. 2021;128(4):521-529. doi:10.1007/s00702-021-02339-7 

7. Anticholinergics  Anticholinergics are highly effective oral drugs for the treatment of dystonia and often are the first choice in individuals with idiopathic dystonia. The most studied drug in this class is Trihexyphenidyl , which can be started with 1 mg at bedtime and then increased slowly to 6 to 8 mg/d divided in 3 or 4 doses.  Adverse effects include cognitive impairment, hallucinations, blurry vision, and urinary retention. Jankovic J. Treatment of dystonia. The Lancet Neurology. 2006;5(10):864-872. doi:10.1016/S1474-4422(06)70574-9 

8. Baclofen Baclofen, a GABA-B receptor agonist, is less effective than anticholinergic drugs in general, but is helpful in individuals who have generalized dystonia or a focal dystonia other than cervical dystonia. Baclofen is also effective for spasticity , making it an option for individuals with spasticity and dystonia or those who have truncal or lower extremity dystonia that does not respond well to other therapies. Side effects such as hallucinations, confusion or mental depression, other mood or mental changes, and severe drowsiness may occur especially in elderly patients. Greene P, Shale H, Fahn S. Analysis of open-label trials in torsion dystonia using high dosages of anticholinergics and other drugs. Mov Disord . 1988;3(1):46-60. doi:10.1002/mds.870030107 

9. Benzodiazepines Benzodiazepines are also commonly used to treat dystonia, clonazepam in particular, because of its long half-life. The risk of substance abuse should be considered, especially in younger males with psychiatric disease. The most common side effect of drowsiness should be considered. Termsarasab P, Thammongkolchai T, Frucht SJ. Medical treatment of dystonia. J Clin Mov Disord . 2016;3:19. doi:10.1186/s40734-016-0047-6 

10. Botulinum Toxin  BTX acts at the neuromuscular junction by cleaving a vesicle-fusion protein, preventing the release of acetylcholine that would lead to muscle contraction  BTX is considered the most effective and well-tolerated treatment for dystonia overall, particularly for individuals with focal or segmental dystonias   BTX side effects may include reactions to the injections ( eg , discomfort, infection, bleeding), excessive dose ( eg , muscle weakness), or local spread of the toxin ( eg , dysphagia when injecting the neck, dry eye when injecting close to the medial canthus). Termsarasab P, Thammongkolchai T, Frucht SJ. Medical treatment of dystonia. J Clin Mov Disord . 2016;3:19. doi:10.1186/s40734-016-0047-6 

11. Deep Brain Stimulation  DBS is useful to treat individuals with different forms of dystonia who have inadequate benefit or intolerable side effects from less invasive treatment. The globus pallidus pars interna ( GPi ) and the subthalamic nucleus are both common targets for treating dystonia with DBS  Mild-to-moderate dysarthria and re-occurrence of dystonic symptoms were the most common adverse effects (approximately 5%) and usually could be corrected by adaptation of the stimulation parameters. Patients with combined dystonias are less likely to benefit from DBS , because the associated neurological symptoms (e.g., hypotonia or ataxia), with the exception of myoclonus, do not respond to pallidal neurostimulation Ostrem JL, Starr PA. Treatment of Dystonia with Deep Brain Stimulation. Neurotherapeutics. 2008;5(2):320-330. doi:10.1016/j.nurt.2008.01.002 

12. Deep Brain Stimulation  Recommendations Patients with primary dystonia experience the most benefit from DBS, whether it is generalized, segmental and focal. GPi DBS should be considered for patients with primary dystonia who do not respond adequately to medical therap y. Clinical practice generally suggests that patients with dystonia should undergo trials of maximally tolerated doses of appropriate medications before undergoing surgery . Medications including one or more of the following classes of drugs: dopaminergic, anticholinergic, and benzodiazepine Previous surgical treatments (i.e., thalamotomy, pallidotomy, peripheral denervation) should not prevent consideration of DBS Screening for psychiatric co-morbidities , including depression and suicide attempts, is recommended. If the premorbid psychiatric symptoms are deemed severe this may be a contraindication to surgery For older patients, comorbidities such as hypertension and cognitive impairment should be taken into account in the risk/benefit analysis. Bronte-Stewart H, Taira T, Valldeoriola F, Merello M, Marks WJ Jr, Albanese A, Bressman S, Moro E. Inclusion and exclusion criteria for DBS in dystonia. Mov Disord . 2011 Jun;26 Suppl 1( Suppl 1):S5-16. doi : 10.1002/mds.23482. PMID: 21692112; PMCID: PMC8478120.

13. Lesion Surgery  Pallidotomies have fallen in popularity since DBS became available, in part because the side effects of lesions are permanent , whereas DBS stimulation-related effects are reversible.  Side effects includes speech problems, facial weakness, and limb paresis. May be preferred by patients who do not want the hassle of permanent indwelling DBS hardware. Pallidotomies remain an important strategy in the treatment of status dystonicus , a life-threatening exacerbation of dystonia. Centen LM, Oterdoom DLM, Tijssen MAJ, Lesman- Leegte I, van Egmond ME, van Dijk JMC. Bilateral Pallidotomy for Dystonia: A Systematic Review. Movement Disorders. 2021;36(3):547-557. doi:10.1002/mds.28384

14. Deep Brain Stimulation vs Lesioning in Movement Disorder Patients When to Consider Surgical Therapies Oral medications are the mainstay of management in movement disorder. Surgical and other advanced treatment options should be considered for patients whose symptoms cannot be adequately managed by oral medications alone. Sharma VD, Patel M, Miocinovic S. Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics. 2020 Oct;17(4):1525-1538. doi : 10.1007/s13311-020-00939-x. Epub 2020 Oct 28. PMID: 33118132; PMCID: PMC7851282.

15. Evolution of Surgical Therapies Sharma VD, Patel M, Miocinovic S. Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics. 2020 Oct;17(4):1525-1538. doi : 10.1007/s13311-020-00939-x. Epub 2020 Oct 28. PMID: 33118132; PMCID: PMC7851282.

16. Deep Brain Stimulation Patient Selection Patients with a diagnosis of idiopathic movement disorder with no significant improvement to oral medications are ideal candidates for DBS therapy Patients with postural instability, uncontrolled neuropsychiatric issues, and multiple comorbidities may be poor candidates Dementia, atypical parkinsonism, and severe psychiatrics comorbidities are contraindications for DBS surgery Sharma VD, Patel M, Miocinovic S. Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics. 2020 Oct;17(4):1525-1538. doi : 10.1007/s13311-020-00939-x. Epub 2020 Oct 28. PMID: 33118132; PMCID: PMC7851282.

17. Deep Brain Stimulation Target Selection Two targets most frequently used for DBS are the globus pallidus interna ( GPi ) and the subthalamic nucleus (STN) The ventral intermediate nucleus of the thalamus ( ViM ) is an established target for tremor control, but it is considered less frequently as it has a limited effect on other motor symptoms and does not improve motor complications Posterior subthalamic area (PSA)/ cZi (caudal zona incerta) has been reported to be an effective target for parkinsonian tremor Sharma VD, Patel M, Miocinovic S. Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics. 2020 Oct;17(4):1525-1538. doi : 10.1007/s13311-020-00939-x. Epub 2020 Oct 28. PMID: 33118132; PMCID: PMC7851282.

18. Deep Brain Stimulation Complications intracranial hemorrhage (1-5%), stroke (0-2%), infection (2-5%), seizure (0.3-5%), perilead edema (3-4%), postoperative confusion (5-26.5%), and rarely death Sharma VD, Patel M, Miocinovic S. Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics. 2020 Oct;17(4):1525-1538. doi : 10.1007/s13311-020-00939-x. Epub 2020 Oct 28. PMID: 33118132; PMCID: PMC7851282.

19. Lesioning Surgery Patient Selection LS can be considered in patients who choose not to or cannot safely undergo DBS surgery and/or have difficulties with regular follow-up programming visits Compared to DBS, successful LS is relatively cheaper and has fewer complications; however LS is not reversible and postprocedure optimization is not possible without revision surgery Criteria for LS candidacy are similar to those of DBS Sharma VD, Patel M, Miocinovic S. Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics. 2020 Oct;17(4):1525-1538. doi : 10.1007/s13311-020-00939-x. Epub 2020 Oct 28. PMID: 33118132; PMCID: PMC7851282.

20. Lesioning Surgery Target Selection Thalamotomy is considered for tremor-predominant disorder Pallidotomy might be a better choice to improve bradykinesia and rigidity Sharma VD, Patel M, Miocinovic S. Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics. 2020 Oct;17(4):1525-1538. doi : 10.1007/s13311-020-00939-x. Epub 2020 Oct 28. PMID: 33118132; PMCID: PMC7851282.

21. Comparison Sharma VD, Patel M, Miocinovic S. Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics. 2020 Oct;17(4):1525-1538. doi : 10.1007/s13311-020-00939-x. Epub 2020 Oct 28. PMID: 33118132; PMCID: PMC7851282.

22. TERIMA KASIH