Tardive dystonia and dyskinesia
Keywords:
tardive dystonia, tardive dyskinesia, clinics, treatmentAbstract
Tardive dyskinesias are so named because they occur late (months or years) after treatment with neuroleptics. They can occur during the course of treatment, but also when the dosage is reduced or the treatment is stopped. They persist for at least one month after stopping the medication that caused the syndrome. Pathogenesis is associated with dopaminergic overactivity, activation of dopamine D2 receptors, and loss of GABA-ergic activity in the subthalamic nucleus. Clinically, dyskinesias manifest as restless movements of the tongue or tic-like movements of the face and clenching of the teeth. Mouth movements are stereotyped and rhythmic, grunting or moaning may be added due to involvement of the upper respiratory tract. Typical orobuccolingual dyskinesia resembles continuous chewing, with the tongue periodically darting out of the mouth. Late dystonia most often manifests as craniocervical dystonia affecting the lower part of the face (mouth, cheeks, tongue, and neck), blepharospasm, and cervical dystonia in various combinations. Dysphagia with swallowing disorder often occurs. Late movements are characterized by a diverse mixture of orofacial or other localized dystonia, athetosis, chorea, myoclonus, tics, facial grimacing, and stereotypies.
Treatment initially involves slow and gradual tapering of neuroleptic therapy, if possible. Clonazepam, valproates, vigabatrin, and baclofen can be used, but they are less effective. Tetrabenazine is administered in increasing doses of 25 mg daily until an effect is obtained. Valbenazine and deutetrabenazine are selective vesicular monoamine transporter type 2 (VMAT2) inhibitors that are effective and have fewer side effects. In isolated cases there has been a positive result from the administration of propranolol, clonidine, levetiracetam, amantadine, nifedipine, verapamil, opiates and lithium. Anticholinergic drugs affect dystonia but worsen tardive choreic dyskinesias and do not affect akathisia. Botulinum toxin primarily affects dystonias. Different movements are affected by different medications. The prognosis is different, ranging from spontaneous disappearance of dyskinesias up to 2 years after stopping treatment in 30% of patients to irreversible forms. Dystonic movements are often permanent.
In conclusion, the use of atypical neuroleptics, the careful assessment of the need for treatment with them and the approval of the modern group of selective inhibitors of the vesicular monoamine transporter type 2 (VMAT2) for the treatment of the late syndrome give hope for a better prognosis of the late syndrome.
References
Aquino, C.C.H., Lang, A.E. Tardive dyskinesia syndromes: current concepts. Parkinsonism and Related Disorders, 2014, 20, suppl 1, S113-S117.
Caroff, S.N. Recent advances in the pharmacology of tardive dyskinesia. Clinical Psychopharmacology and Neuroscience, 2020, 18, 4, 493-506.
Caroff, S.N., Aggarwal, S., Yonan, C. Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review. J. Comp. Eff. Res., 2018, 7, 2, 135-148.
Clow, A. The consequences of chronic exposure to neuroleptics in the rat. In: Disorders of movement: Clinical, pharmacological and physiological aspects. Quinn, N.P., Jenner, P.G. eds., Academic Press, London, Harcourt Brace Jovanovich Publishers, 1989, 395-407.
Dhaenens, C.M., Krystkowiak, P., Douay, X., Charpentier, P., Bele, S., Destee, A., Sablonniere, B. Clinical and genetic evaluation in a French population presenting with primary focal dystonia. Movement Disorders, 2005, 20, 7, 822-825.
Fahn, S. Clinical features and diagnosis of Huntington’s disease, tardive dyskinesia and dystonias. In: Neurotransmitters and neuropeptides. Teychenne, P.F. ed., Taipei, Excerptra Medica, Asia Pacific Congress Series No 32, 1983, 34-40.
Fahn, S., Burke, R.E. Tardive dyskinesia and other neurolepticinduced syndromes. In: Merritt’s neurology-11th ed. Rowland, L.P. ed., Philadelphia, Lippincott Williams & Wilkins, 2005, 849-852.
Faurbye, A., Rasch, P.J., Peterson, P.B., Brandborg, G., Pakkenberg, H. Neurological symptoms in pharmacotherapy of psychoses. Acta Psychiatrica Scandinavica, 1964, 40, 1, 10-27.
Frei, K., Truong, D.D., Fahn, S., Jankovic, J., Hauser, R.A. The nosology of tardive syndromes. Journal of the Neurological Sciences, 2018, 389, 10-16.
Goetz, C.G., Horn, S. Tardive dyskinesia. In: Movement Disorders, Neurologic Principles and Practice. Watts, R.L., Koller, W.C. eds., New York, McGraw-Hill, 2004, 629-637.
Jenner, P., Marsden, C.D. The organization of neuronal systems in basal ganglia and their involvement in extrapyramidal disease. In: Neurotransmitters and neuropeptides. Teychenne, P.F. ed., Taipei, Excerptra Medica, Asia Pacific Congress Series No 32, 1983, 1-11.
Kim, A.P., Baker, D.E., Levien, T.L. VMAT2 Inhibitors: New drugs for the treatment of tardive dyskinesia. Consult. Pharm., 2018, 33, 4, 201-209.
Kuo, S.H., Jankovic, J. Tardive gait. Clinical Neurology and Neurosurgery, 2008, 110, 198-201.
Lehosit, J.B., Cloud, L.J. Gastrointestinal complications of movement disorders. In: Movement disorders in neurologic and systemic disease. Poewe, W., Jankovic, J. eds., New York, Cambridge University Press, 2014, 383-397.
Le Witt, P.A. Dystonia caused by drugs. In: Handbook of dystonia. Tsui, J.K.C., Calne, D.B. eds., New York, Marcel Dekker, Inc., 1995, 227-240.
MacNeil, R.R., Muller, D.J. Genetics of common antipsychoticinduced adverse effects. Molecular Neuropsychiatry, 2016, 2, 61-78.
Mehanna, R., Jankovic, J. Respiratory complications of movement disorders. In: Movement disorders in neurologic and systemic disease. Poewe, W., Jankovic, J. eds., New York, Cambridge University Press, 2014, 398-418.
Mehta, S.H., Sethi, K.D. Drug induced movement disorders In: Movement disorders in neurologic and systemic disease. Poewe, W., Jankovic, J. eds., New York, Cambridge University Press, 2014, 203-219.
Ramdhani, R., Frucht, S.J. Movement disorders emergencies. In: Movement disorders in neurologic and systemic disease. Poewe, W., Jankovic, J. eds., New York, Cambridge University Press, 2014, 419-441.
Revuelta, G.J., Cloud, L., Aia, P.G., Factor, S.A. Tardive dyskinesias. In: Hyperkinetic movement disorders. Differential diagnosis and treatment, Albanese, A., Jankovic, J. eds., Oxford, Wiley-Blackwell, 2012, 331-352.
Roberts, K., Lynch, T. Movement disorders following non-metal intoxications. In: Movement disorders in neurologic and systemic disease. Poewe, W., Jankovic, J. eds., New York, Cambridge University Press, 2014, 234-246.
Ropper, A.H., Samuels, M.A. Tremor, myoclonus, focal dystonias and tics. In: Adams and Victors Principles of Neurology-9th ed. New York, McGraw-Hill, Inc., 2009, 89-110.
Schonecker, M. Ein eigentumliches Syndrom im ovalen Bereich bei Megaphen Applikation. Nervenarzt, 1957, 28, 35-42.
Scorr, L.M., Factor, S.A. VMAT2 inhibitors for the treatment of tardive dyskinesia. J. Neurol. Sci, 2018, 389, 43-47.
Tarsy, D. Neuroleptic-induced movement disorders. In: Disorders of movement: Clinical, pharmacological and physiological aspects. Quinn, N.P., Jenner, P.G. eds., London, Academic Press, Harcourt Brace Jovanovich Publishers, 1989, 361-393.
Tarsy, D., Baldessarini, R.J. Epidemiology of tardive dyskinesia: Is risk declining with modern antipsychotics? Movement Disorders, 2006, 21, 5, 589-598.
