Results of treatment with intravenous amantadine sulfate (PK-Merz) patients with chronic disorders of consciousness

Close metadata

Recommended articles:

Neuromodulatory pharmacotherapy individualization in prolonged and chronic consciousness disorders after severe traumatic brain injury. Burdenko's Journal of Neurosurgery. 2024;(3):74-80

Diagnostic criteria for prolonged and chronic disturbances of consciousness after aneurysmal subarachnoid hemorrhages. Burdenko's Journal of Neurosurgery. 2024;(4):117-121

The FOUR scale in intensive care and rehabilitation of patients with acute cerebral injury. The first results of a two-stage study. Russian Journal of Anesthesiology and Reanimatology. 2025;(1):21-29

The article presents literature review of the recent publications devoted to the drugs with dopaminergic, antiglutamatergic and GABA-ergic effects in the treatment of patients with vegetative state/areactive wakefulness syndrome (VS/AWS). The authors analyzed their own results of the effects of intravenous form of amantadine sulfate (PK Merz) in 142 VS/AWS patients caused by different etiological factors. Depending on the dominant neurological symptoms, patients were divided into three main groups: areactive type of course (group 1 — 61 patients), predominance of primitive limbic reactions (group 2 — 35 patients) and predominance of extrapyramidal symptoms (group 3 — 46 patients). Therapy results were evaluated one month later by CRS-R scale, which showed that the most distinct positive dynamics was observed in group 3.

Keywords:

chronic disorders of consciousness

vegetative state

areactive wakefulness syndrome

minimally consciousness state

dopaminergic drugs

antiglutamatergic drugs

amantadine sulfate

Authors:

Kondratieva E.A.

Polenov Neurosurgical Institute branch of Almazov National Medical Research Centre

Kondratev S.A.

Polenov Neurosurgical Institute branch of Almazov National Medical Research Centre

Denisova A.A.

Admiral Makarov State University of Maritime and Inland Shipping

Ivanova N.E.

Polenov Russian Scientific Research Neurosurgical Institute — branch of Almazov National Medical Research Center

Kondratiev A.N.

Polenov Neurosurgical Institute

SPIN RSCI: 8235-9765
ORCID: 0000-0002-7648-2208

Received:

23.10.2020

Accepted:

09.11.2020

List of references:

Piradov MA, Suponeva NA, Voznjuk IA, et al. Chronic disorders of consciousness: terminology and diagnostic criteria The results of the first meeting of the Russian Working Group for Chronic Disorders of Consciousness. Annaly Klinicheskoj i Jeksperimental’noj Nevrologii. 2020;14(1):5-16. (In Russ.). https://doi.org/10.25692/ACEN.2020.1.1
Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018;91:450-460. https://doi.org/10.1212/wnl.0000000000005926
Working Party of the Royal College of Physicians. The vegetative state: guidance on diagnosis and management. A report of a working party of the Royal College of Physicians. Clin Med (Lond). 2019;3(3):249-254. https://doi.org/10.7861/clinmedicine.3-3-249
Kondziella D, Bender A, Diserens K, et al. European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness. Eur J Neurol. 2020;27(5):741-756. https://doi.org/10.1111/ene.14151
Laureys S, Celesia GG, Cohadon F, et al. Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome. BMC Medical. 2010;8:68. https://doi.org/10.1186/1741-7015-8-68
Van Erp WS, Lavrijsen JC, Vos M, et al.The vegetative state: prevalence, misdiagnosis, and treatment limitations. J Am Med Dir Assoc. 2015;16(1):85.e9–85.e14. https://doi.org/10.1016/j.jamda.2014.10.014
Piradov MA, Suponeva NA, Sergeev DV, et al. Structural and functional basis of chronic disorders of consciousness. The Annals Clinical and Experimental Neurology. 2018;12(5):6-15. (In Russ.). https://doi.org/10.25692/ACEN.2018.5.1
Kondrat’eva EA, Avdjunina IA, Kondrat’ev AN, et al. Vegetative State: Difficulty in Identifying Consciousness and Predicting Outcome. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk. 2016;71(4):273-280. (In Russ.). https://doi.org/10.15690/vramn728
Schiff N, Giacino J, Laureys S. Therapeutic interventions in patients with prolonged disorders of consciousness. Lancet Neurol. 2019;18(6):600-614. https://doi.org/10.1016/S1474-4422(19)30031-6
Aleksandrova EV, Zaytsev OS, Potapov AA. Clinical syndromes of neurotransmitter system dysfunction in severe brain injury. S.S. Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2015;115(7):40-46. (In Russ.). https://doi.org/10.17116/jnevro20151157140-46
Kondrat’eva EA, Borovikova VN, Kondrat’ev SA, et al. The role of rivastigmine (exelon) in the treatment of consequences of cranial-brain trauma. S.S. Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2009;109(1):55-58. (In Russ.).
Thibaut A, Schiff N, Giacino J,et al. Therapeutic interventions in patients with prolonged disorders of consciousness. Lancet Neurol. 2019;18(6):600-614. https://doi.org/10.1016/S1474-4422(19)30031-6
Ciurleo R, Bramanti R, Calabro S. Pharmacotherapy for disorders of consciousness: are ‘awakening’ drugs really a possibility? Drugs. 2013;73(17):1849-1862. https://doi.org/10.1007/s40265-013-0138-8
Calabro RS, Arico I, De Salvo S, et al. Transient awakening from vegetative state: is high — dose zolpidem more effective? Psychiatry Clin Neurosci. 2015;69(2):122-123. https://doi.org/10.1111/pcn.12215
Clauss RPW, Nel W. Drug induced arousal from the permanent vegetative state. NeuroRehabilitation. 2006;21(2):23-28.
Dolce G, Lucca LF, Quintieri M, et al. Dysautonomia and clinical outcome in vegetative state. Journal Neurotrauma. 2008;25:1079-1082. https://doi.org/10.1089/neu.2008.0536
Alexandrova EV, Tonoyan AS, Sychev AA, Kryukova KK. The activity of sympathoadrenal system in the acute phase of severe traumatic brain injury: the importance of neuroanatomical factors. Vestnik Rossijskogo Fonda Fundamental’nyh Issledovanij. 2016;90(2):41-49. (In Russ.).
Grechko AV, Kiryachkov YuYu, Petrova MV. Modern aspects of the relationship between the functional state of the autonomic nervous system and clinical and laboratory indices of the body’s homeostasis in brain injuries. Vestnik Intensivnoj Terapii. 2018;(2):79-86. (In Russ.).
Lucca LF, Lofaro D, Pignolo L, et al. Paroxysmal Sympathetic Hyperactivity Rate in Vegetative or Minimally Conscious State after Acquired Brain Injury Evaluated by Paroxysmal Sympathetic Hyperactivity Assessment Measure. J Neurotrauma. 2019;36(16):2430-2434. https://doi.org/10.1089/neu.2018.5963
Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: disorders of consciousness: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018;91(10):450-460. https://doi.org/10.1212/WNL.0000000000005926
Giacino JT, Whyte J, Bagiella E, et al. Placebo controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012;366(9):819-826. https://doi.org/10.1056/NEJMoa1102609
Gosseries O, Charland-Verville V, Thonnard M, et al. Amantadine, apomorphine and zolpidem in the treatment of disorders of consciousness. Curr Pharm Des. 2014;20(26)):4167-4184.
Kong M, Ba M, Ren C, et al. An updated meta-analysis of amantadine for treating dyskinesia in Parkinson’s disease. Oncotarget. 2017;8(34):57316-57326. https://doi.org/10.18632/oncotarget.17622
Gao Y, Zhang Y, Li Z, et al.Persistent vegetative state after severe cerebral hemorrhage treated with amantadine: A retrospective controlled study. Medicine (Baltimore). 2020;99(33):e21822. https://doi.org/10.1097/MD.0000000000021822
Zafonte R, Watanabe T, Mann N. Amantadine: a potential treatment for the minimally conscious state. Brain Injury. 1998;12(7):617-621. https://doi.org/10.1080/02699059812238
Reynolds JC, Rittenberger JC, Callaway CW. Methylphenidate and amantadine to stimulate reawakening in comatose patients resuscitated from cardiac arrest. Resuscitation. 2013;84(6):818-824. https://doi.org/10.1016/j.resuscitation.2012.11.014
Lehnerer SM, Scheibe F, Buchert R, et al. Awakening with amantadine from a persistent vegetative state after subarachnoid haemorrhage. BMJ Case Reports. 2017;2017:bcr-2017-220305.
Horiguchi J, Inami Y, Shoda T. Effects of long — term amantadine treatment on clinical symptoms and EEG of a patient in a vegetative state. Clinical Neuropharmacol. 1990;13(1):84-88. https://doi.org/10.1097/00002826-199002000-00009
Estraneo A, Pascarella A, Moretta P, et al. Clinical and electroencephalographic on — off e ect of amantadine in chronic non — traumatic minimally conscious state. J Neurol. 2015;262(6):1584-1586. https://doi.org/10.1007/s00415-015-7771-y
Schnakers C, Hustinx R, Vandewalle G, et al. Measuring the effect of amantadine in chronic anoxic minimally conscious state. J Neurol Neurosurg Psychiatry. 2008;79(2):225-227. https://doi.org/10.1136/jnnp.2007.124099
Stelmaschuk S, Will MC, Meyers T. Amantadine to treat cognitive dysfunction in moderate to severe traumatic brain injury. J Trauma Nurs. 2015;22(4):194-203. https://doi.org/10.1097/JTN.0000000000000138
Belkin AA, Shchegolev AV, Kondratyev AN, Bubnova ID. Use of amantadine sulfate (pk.-merz) during coma emergence: results of a multicenter study. Anesteziologija i Reanimatologija. 2008;(2):70-72. (In Russ.).
Cheliapina MV, Sharova EV, Zaĭtsev OS. Clinical and electroencephalographic effects of amantadine sulfate (pk-merz) on consciousness disorders due to the severe traumatic brain injury. S.S. Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 2011;111(5):24-28. (In Russ.).
Zaitsev OS, Tsarenko SV, Chelyapina MV, et al. Issues of the accounting of a weak neurotransmitter component in the pharmacotherapy of postcomatose states. Nevrologija, Nejropsihiatrija, Psihosomatika. 2016;8(4):87-90. (In Russ.).
Zaitsev OS, Potapov AA, Likhterman LB, et al. Psychopathological consequences of severe diffuse and focal brain trauma. Russian Neurosurgical Journal named after Professor A.L. Polenova. 2018;(10Specvyp):90. (In Russ.).
Chelyapina MV, Sharova EV, Zaitsev OS. Clinical-encephalographic syndrome of dopamine deficiency in patients with depressed consciousness after severe brain injury. S.S. Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova2015;115(4):9-15. (In Russ.). https://doi.org/10.17116/jnevro2015115419-15
Mochalova EG, Legostaeva LA, Zimin AA, et al. The Russian version of Coma Recovery Scale-revised — a standardized method for assessment of patients with disorders of consciousness. S.S. Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2018(2):25-31. (In Russ.). https://doi.org/10.17116/jnevro20181183225-31
Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale — Revised: measurement char — acteristics and diagnostic utility. Arch Phys Med Rehabil. 2004;85(12):2020-2029. https://doi.org/10.1016/j.apmr.2004.02.033
Xia X, Yang Y, Guo Y, et al. Current Status of Neuromodulatory Therapies for Disorders of Consciousness. Neurosci Bull. 2018;34(4):615-625. https://doi.org/10.1007/s12264-018-0244-4
Schiff ND. Recovery of consciousness after brain injury: a mesocircuit hypothesis. Trends Neurosci. 2010;33(1):1-9. https://doi.org/10.1016/j.tins.2009.11.002

Close metadata