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Table of Contents
Vol. 88, No. 4, 2010
Issue release date: July 2010
Free Access
Stereotact Funct Neurosurg 2010;88:199–207
(DOI:10.1159/000314354)

Vegetative State and Minimally Conscious State: A Review of the Therapeutic Interventions

Georgiopoulos M.a · Katsakiori P.a · Kefalopoulou Z.a · Ellul J.b · Chroni E.b · Constantoyannis C.a
aFunctional Neurosurgery Unit, Department of Neurosurgery, and bDepartment of Neurology, Medical School of Patras, Patras, Greece
email Corresponding Author

Abstract

Background/Aims: The purpose of the present article is a systematic review of the proposed medical or surgical treatments in patients in chronic vegetative state (VS) or minimally conscious state (MCS), as well as of their mechanisms of action and limitations. Methods: For this review, we have agreed to include patients in VS or MCS having persisted for over 6 months in posttraumatic cases, and over 3 months in nontraumatic cases, before the time of intervention. Searches were independently conducted by 2 investigators between May 2009 and September 2009 in the following databases: Medline, Web of Science and the Cochrane Library. The electronic search was complemented by cross-checking the references of all relevant articles. Overall, 16 papers were eligible for this systematic review. Results: According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. Conclusion: The treatments proposed for disorders of consciousness have not yet gained the level of ‘evidence-based treatments’; moreover, the studies to date have led to inconclusiveness. The published therapeutic responses must be substantiated by further clinical studies of sound methodology.


 goto top of outline Key Words

  • Vegetative state
  • Minimally conscious state
  • Consciousness
  • Treatment outcome

 goto top of outline Abstract

Background/Aims: The purpose of the present article is a systematic review of the proposed medical or surgical treatments in patients in chronic vegetative state (VS) or minimally conscious state (MCS), as well as of their mechanisms of action and limitations. Methods: For this review, we have agreed to include patients in VS or MCS having persisted for over 6 months in posttraumatic cases, and over 3 months in nontraumatic cases, before the time of intervention. Searches were independently conducted by 2 investigators between May 2009 and September 2009 in the following databases: Medline, Web of Science and the Cochrane Library. The electronic search was complemented by cross-checking the references of all relevant articles. Overall, 16 papers were eligible for this systematic review. Results: According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. Conclusion: The treatments proposed for disorders of consciousness have not yet gained the level of ‘evidence-based treatments’; moreover, the studies to date have led to inconclusiveness. The published therapeutic responses must be substantiated by further clinical studies of sound methodology.

Copyright © 2010 S. Karger AG, Basel


 goto top of outline References
  1. Multi-Society Task Force on PVS: Medical aspects of the persistent vegetative state. Part 1. N Engl J Med 1994;330:1499–1508.
  2. Multi-Society Task Force on PVS: Medical aspects of the persistent vegetative state. Part 2. N Engl J Med 1994;330:1572–1579.
  3. Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, Zasler ND: The minimally conscious state: definition and diagnostic criteria. Neurology 2002;58:349–353.
  4. The vegetative state: guidance on diagnosis and management. Clin Med 2003;3:249–254.
  5. Plum F, Posner JB: The Diagnosis of Stupor and Coma, ed 3. Philadelphia, Davis, 1980.
  6. Giacino JT, Trott CT: Rehabilitative management of patients with disorders of consciousness: grand rounds. J Head Trauma Rehabil 2004;19:254–265.
  7. Zeman A: What is consciousness and what does it mean for the persistent vegetative state? Adv Clin Neurosci Rehabil 2003;3:12–14.
  8. Kanno T, Morita I, Yamaguchi S, Yokoyama T, Kamei Y, Anil SM, Karagiozov KL: Dorsal column stimulation in persistent vegetative state. Neuromodulation 2009;12:33–38.
  9. Adams JH, Graham DI, Jennett B: The neuropathology of the vegetative state after an acute brain insult. Brain 2000;123:1327–1338.
  10. Kampfl A, Franz G, Aichner F, Pfausler B, Haring HP, Felber S, Luz G, Schocke M, Schmutzhard E: The persistent vegetative state after closed head injury: clinical and magnetic resonance imaging findings in 42 patients. J Neurosurg 1998;88:809–816.
  11. Matsuda W, Komatsu Y, Yanaka K, Matsumura A: Levodopa treatment for patients in persistent vegetative or minimally conscious states. Neuropsychol Rehabil 2005;15:414–427.
  12. Matsuda W, Matsumura A, Komatsu Y, Yanaka K, Nose T: Awakenings from persistent vegetative state: report of three cases with parkinsonism and brain stem lesions on MRI. J Neurol Neurosurg Psychiatry 2003;74:1571–1573.
  13. Haig AJ, Ruess JM: Recovery from vegetative state of six months’ duration associated with Sinemet (levodopa/carbidopa). Arch Phys Med Rehabil 1990;71:1081–1083.
  14. Koeda T, Takeshita K: A case report of remarkable improvement of motor disturbances with L-DOPA in a patient with post-diffuse axonal injury. Brain Dev 1998;20:124–126.
  15. Horiguchi J, Inami Y, Shoda T: Effects of long-term amantadine treatment on clinical symptoms and EEG of a patient in a vegetative state. Clin Neuropharmacol 1990;13:84–88.
  16. Schnakers C, Hustinx R, Vandewalle G, Majerus S, Moonen G, Boly M, Vanhaudenhuyse A, Laureys S: Measuring the effect of amantadine in chronic anoxic minimally conscious state. J Neurol Neurosurg Psychiatry 2008;79:225–227.
  17. Clauss R, Nel W: Drug-induced arousal from the permanent vegetative state. NeuroRehabilitation 2006;21:23–28.
  18. Shames JL, Ring H: Transient reversal of anoxic brain injury-related minimally conscious state after zolpidem administration: a case report. Arch Phys Med Rehabil 2008;89:386–388.
  19. Brefel-Courbon C, Payoux P, Ory F, Sommet A, Slaoui T, Raboyeau G, Lemesle B, Puel M, Montastruc JL, Demonet JF, Cardebat D: Clinical and imaging evidence of zolpidem effect in hypoxic encephalopathy. Ann Neurol 2007;62:102–105.
  20. Cohen SI, Duong TT: Increased arousal in a patient with anoxic brain injury after administration of zolpidem. Am J Phys Med Rehabil 2008;87:229–231.
  21. Whyte J, Myers R: Incidence of clinically significant responses to zolpidem among patients with disorders of consciousness: a preliminary placebo controlled trial. Am J Phys Med Rehabil 2009;88:410–418.
  22. Singh R, McDonald C, Dawson K, Lewis S, Pringle AM, Smith S, Pentland B: Zolpidem in a minimally conscious state. Brain Inj 2008;22:103–106.
  23. Cooper EB, Scherder EJ, Cooper JB: Electrical treatment of reduced consciousness: experience with coma and Alzheimer’s disease. Neuropsychol Rehabil 2005;15:389–405.
  24. Schiff ND, Giacino JT, Kalmar K, Victor JD, Baker K, Gerber M, Fritz B, Eisenberg B, Biondi T, O’Connor J, Kobylarz EJ, Farris S, Machado A, McCagg C, Plum F, Fins JJ, Rezai AR: Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature 2007;448:600–603.
  25. Canavero S, Massa-Micon B, Cauda F, Montanaro E: Bifocal extradural cortical stimulation-induced recovery of consciousness in the permanent post-traumatic vegetative state. J Neurol 2009;256:834–836.
  26. Sara M, Pistoia F, Mura E, Onorati P, Govoni S: Intrathecal baclofen in patients with persistent vegetative state: 2 hypotheses. Arch Phys Med Rehabil 2009;90:1245–1249.
  27. Matsuda W, Sugimoto K, Sato N, Watanabe T, Yanaka K, Matsumura A, Nose T: A case of primary brainstem injury recovered from persistent vegetative state after L-DOPA administration (in Japanese). No To Shinkei 1999;51:1071–1074.
  28. Giacino JT, Kalmar K, Whyte J: The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil 2004;85:2020–2029.
  29. Hagan C, Malkmus D, Durham P: Levels of cognitive function; in Professional Staff Association (eds): Rehabilitation of the Head-Injured Adult. Comprehensive Physical Management. Downey, Rancho Los Amigos Hospital, 1979.
  30. Canavero S: Textbook of therapeutic cortical stimulation. Hauppauge, Nova Science, 2009.
  31. Canavero S, Bonicalzi V, Intonti S, Crasto S, Castellano G: Effects of bilateral extradural cortical stimulation for plegic stroke rehabilitation: case report. Neuromodulation 2006;9:28–33.

    External Resources

  32. Higashi K, Sakata Y, Hatano M, Abiko S, Ihara K, Katayama S, Wakuta Y, Okamura T, Ueda H, Zenke M, Aoki H: Epidemiological studies on patients with a persistent vegetative state. J Neurol Neurosurg Psychiatry 1977;40:876–885.
  33. Schiff ND: DBS disorders of consciousness; in Lozano AM, Gildenberg PL, Tasker RR (eds): Textbook of Stereotactic and Functional Neurosurgery, ed 2. Berlin, Springer, 2009, pp 2981–2990.
  34. McLardy T, Ervin F, Mark V, Scoville W, Sweet W: Attempted inset-electrodes-arousal from traumatic coma: neuropathological findings. Trans Am Neurol Assoc 1968;93:25–30.
  35. Hassler R, Ore GD, Dieckmann G, Bricolo A, Dolce G: Behavioural and EEG arousal induced by stimulation of unspecific projection systems in a patient with post-traumatic apallic syndrome. Electroencephalogr Clin Neurophysiol 1969;27:306–310.
  36. Hassler R, Ore GD, Bricolo A, Dieckmann G, Dolce G: EEG and clinical arousal induced by bilateral long-term stimulation of pallidal systems in traumatic vigil coma. Electroencephalogr Clin Neurophysiol 1969;27:689–690.
  37. Sturm V, Kühner A, Schmitt HP, Assmus H, Stock G: Chronic electrical stimulation of the thalamic-unspecific activating system in a patient with coma due to midbrain and upper brain stem infarction. Acta Neurochir (Wien) 1979;47:235–244.
  38. Tsubokawa T, Yamamoto T, Katayama Y, Hirayama T, Maejima S, Moriya T: Deep-brain stimulation in a persistent vegetative state: follow-up results and criteria for selection of candidates. Brain Inj 1990;4:315–327.
  39. Cohadon F, Richer E: Deep cerebral stimulation in patients with post-traumatic vegetative state: 25 cases (in French). Neurochirurgie 1993;39:281–292.
  40. Zafonte RD, Watanabe T, Mann NR: Amantadine: a potential treatment for the minimally conscious state. Brain Inj 1998;12:617–621.
  41. Clauss RP, Nel WH: Effect of zolpidem on brain injury and diaschisis as detected by 99mTc HMPAO brain SPECT in humans. Arzneimittelforschung 2004;54:641–646.
  42. Clauss RP, Güldenpfennig WM, Nel HW, Sathekge MM, Venkannagari RR: Extraordinary arousal from semi-comatose state on zolpidem: a case report. S Afr Med J 2000;90:68–72.
  43. Clauss RP, Dormehl IC, Kilian E, Louw WK, Nel WH, Oliver DW: Cerebral blood perfusion after treatment with zolpidem and flumazenil in the baboon. Arzneimittelforschung 2002;52:740–744.
  44. Cohen L, Chaaban B, Habert MO: Transient improvement of aphasia with zolpidem. N Engl J Med 2004;350:949–950.
  45. Schiff ND: Central thalamic deep-brain stimulation in the severely injured brain: rationale and proposed mechanisms of action. Ann NY Acad Sci 2009;1157:101–116.
  46. Schiff ND, Fins JJ: Deep brain stimulation and cognition: moving from animal to patient. Curr Opin Neurol 2007;20:638–642.
  47. Boly M, Faymonville ME, Peigneux P, Lambermont B, Damas P, del Fiore G, Degueldre C, Franck G, Luxen A, Lamy M, Moonen G, Maquet P, Laureys S: Auditory processing in severely brain-injured patients: differences between the minimally conscious state and the persistent vegetative state. Arch Neurol 2004;61:233–238.
  48. Coleman MR, Rodd JM, Davis MH, Johnsrude IS, Menon DK, Pickard JD, Owen AM: Do vegetative patients retain aspects of language comprehension? Evidence from fMRI. Brain 2007;130:2494–2507.
  49. Di HB, Yu SM, Weng XC, Laureys S, Yu D, Li JQ, Qin PM, Zhu YH, Zhang SZ, Chen YZ: Cerebral response to patient’s own name in the vegetative and minimally conscious states. Neurology 2007;68:895–899.
  50. Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD: Detecting awareness in the vegetative state. Science 2006;313:1402.
  51. Schiff ND, Rodriguez-Moreno D, Kamal A, Kim KH, Giacino JT, Plum F, Hirsch J: fMRI reveals large-scale network activation in minimally conscious patients. Neurology 2005;64:514–523.
  52. Schiff ND, Plum F: The role of arousal and ‘gating’ systems in the neurology of impaired consciousness. J Clin Neurophysiol 2000;17:438–452.
  53. Shirvalkar P, Seth M, Schiff ND, Herrera DG: Cognitive enhancement with central thalamic electrical stimulation. Proc Natl Acad Sci USA 2006;103:17007–17012.
  54. Krout KE, Belzer RE, Loewy AD: Brainstem projections to midline and intralaminar thalamic nuclei of the rat. J Comp Neurol 2002;448:53–101.
  55. Baars BJ, Ramsoy TZ, Laureys S: Brain, conscious experience and the observing self. Trends Neurosci 2003;26:671–675.
  56. Laureys S: The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci 2005;9:556–559.
  57. Richard I, Menei P: Intrathecal baclofen in the treatment of spasticity, dystonia and vegetative disorders. Acta Neurochir Suppl 2007;97:213–218.
  58. Sara M, Sacco S, Cipolla F, Onorati P, Scoppetta C, Albertini G, Carolei A: An unexpected recovery from permanent vegetative state. Brain Inj 2007;21:101–103.
  59. Taira T, Hori T: Intrathecal baclofen in the treatment of post-stroke central pain, dystonia, and persistent vegetative state. Acta Neurochir Suppl 2007;97:227–229.
  60. Lombardi F, Taricco M, de Tanti A, Telaro E, Liberati A: Sensory stimulation of brain-injured individuals in coma or vegetative state: results of a Cochrane systematic review. Clin Rehabil 2002;16:464–472.

 goto top of outline Author Contacts

Constantine Constantoyannis, Assistant Professor
Functional Neurosurgery Unit, Department of Neurosurgery
Medical School of Patras
GR–26500 Patras (Greece)
Tel. +30 26 1099 9495, Fax +30 26 1099 2997, E-Mail cconst@med.upatras.gr


 goto top of outline Article Information

Received: December 1, 2009
Accepted after revision: March 14, 2010
Published online: May 12, 2010
Number of Print Pages : 9
Number of Figures : 0, Number of Tables : 2, Number of References : 60


 goto top of outline Publication Details

Stereotactic and Functional Neurosurgery

Vol. 88, No. 4, Year 2010 (Cover Date: July 2010)

Journal Editor: Roberts D.W. (Lebanon, N.H.)
ISSN: 1011-6125 (Print), eISSN: 1423-0372 (Online)

For additional information: http://www.karger.com/SFN


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background/Aims: The purpose of the present article is a systematic review of the proposed medical or surgical treatments in patients in chronic vegetative state (VS) or minimally conscious state (MCS), as well as of their mechanisms of action and limitations. Methods: For this review, we have agreed to include patients in VS or MCS having persisted for over 6 months in posttraumatic cases, and over 3 months in nontraumatic cases, before the time of intervention. Searches were independently conducted by 2 investigators between May 2009 and September 2009 in the following databases: Medline, Web of Science and the Cochrane Library. The electronic search was complemented by cross-checking the references of all relevant articles. Overall, 16 papers were eligible for this systematic review. Results: According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. Conclusion: The treatments proposed for disorders of consciousness have not yet gained the level of ‘evidence-based treatments’; moreover, the studies to date have led to inconclusiveness. The published therapeutic responses must be substantiated by further clinical studies of sound methodology.



 goto top of outline Author Contacts

Constantine Constantoyannis, Assistant Professor
Functional Neurosurgery Unit, Department of Neurosurgery
Medical School of Patras
GR–26500 Patras (Greece)
Tel. +30 26 1099 9495, Fax +30 26 1099 2997, E-Mail cconst@med.upatras.gr


 goto top of outline Article Information

Received: December 1, 2009
Accepted after revision: March 14, 2010
Published online: May 12, 2010
Number of Print Pages : 9
Number of Figures : 0, Number of Tables : 2, Number of References : 60


 goto top of outline Publication Details

Stereotactic and Functional Neurosurgery

Vol. 88, No. 4, Year 2010 (Cover Date: July 2010)

Journal Editor: Roberts D.W. (Lebanon, N.H.)
ISSN: 1011-6125 (Print), eISSN: 1423-0372 (Online)

For additional information: http://www.karger.com/SFN


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Multi-Society Task Force on PVS: Medical aspects of the persistent vegetative state. Part 1. N Engl J Med 1994;330:1499–1508.
  2. Multi-Society Task Force on PVS: Medical aspects of the persistent vegetative state. Part 2. N Engl J Med 1994;330:1572–1579.
  3. Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, Zasler ND: The minimally conscious state: definition and diagnostic criteria. Neurology 2002;58:349–353.
  4. The vegetative state: guidance on diagnosis and management. Clin Med 2003;3:249–254.
  5. Plum F, Posner JB: The Diagnosis of Stupor and Coma, ed 3. Philadelphia, Davis, 1980.
  6. Giacino JT, Trott CT: Rehabilitative management of patients with disorders of consciousness: grand rounds. J Head Trauma Rehabil 2004;19:254–265.
  7. Zeman A: What is consciousness and what does it mean for the persistent vegetative state? Adv Clin Neurosci Rehabil 2003;3:12–14.
  8. Kanno T, Morita I, Yamaguchi S, Yokoyama T, Kamei Y, Anil SM, Karagiozov KL: Dorsal column stimulation in persistent vegetative state. Neuromodulation 2009;12:33–38.
  9. Adams JH, Graham DI, Jennett B: The neuropathology of the vegetative state after an acute brain insult. Brain 2000;123:1327–1338.
  10. Kampfl A, Franz G, Aichner F, Pfausler B, Haring HP, Felber S, Luz G, Schocke M, Schmutzhard E: The persistent vegetative state after closed head injury: clinical and magnetic resonance imaging findings in 42 patients. J Neurosurg 1998;88:809–816.
  11. Matsuda W, Komatsu Y, Yanaka K, Matsumura A: Levodopa treatment for patients in persistent vegetative or minimally conscious states. Neuropsychol Rehabil 2005;15:414–427.
  12. Matsuda W, Matsumura A, Komatsu Y, Yanaka K, Nose T: Awakenings from persistent vegetative state: report of three cases with parkinsonism and brain stem lesions on MRI. J Neurol Neurosurg Psychiatry 2003;74:1571–1573.
  13. Haig AJ, Ruess JM: Recovery from vegetative state of six months’ duration associated with Sinemet (levodopa/carbidopa). Arch Phys Med Rehabil 1990;71:1081–1083.
  14. Koeda T, Takeshita K: A case report of remarkable improvement of motor disturbances with L-DOPA in a patient with post-diffuse axonal injury. Brain Dev 1998;20:124–126.
  15. Horiguchi J, Inami Y, Shoda T: Effects of long-term amantadine treatment on clinical symptoms and EEG of a patient in a vegetative state. Clin Neuropharmacol 1990;13:84–88.
  16. Schnakers C, Hustinx R, Vandewalle G, Majerus S, Moonen G, Boly M, Vanhaudenhuyse A, Laureys S: Measuring the effect of amantadine in chronic anoxic minimally conscious state. J Neurol Neurosurg Psychiatry 2008;79:225–227.
  17. Clauss R, Nel W: Drug-induced arousal from the permanent vegetative state. NeuroRehabilitation 2006;21:23–28.
  18. Shames JL, Ring H: Transient reversal of anoxic brain injury-related minimally conscious state after zolpidem administration: a case report. Arch Phys Med Rehabil 2008;89:386–388.
  19. Brefel-Courbon C, Payoux P, Ory F, Sommet A, Slaoui T, Raboyeau G, Lemesle B, Puel M, Montastruc JL, Demonet JF, Cardebat D: Clinical and imaging evidence of zolpidem effect in hypoxic encephalopathy. Ann Neurol 2007;62:102–105.
  20. Cohen SI, Duong TT: Increased arousal in a patient with anoxic brain injury after administration of zolpidem. Am J Phys Med Rehabil 2008;87:229–231.
  21. Whyte J, Myers R: Incidence of clinically significant responses to zolpidem among patients with disorders of consciousness: a preliminary placebo controlled trial. Am J Phys Med Rehabil 2009;88:410–418.
  22. Singh R, McDonald C, Dawson K, Lewis S, Pringle AM, Smith S, Pentland B: Zolpidem in a minimally conscious state. Brain Inj 2008;22:103–106.
  23. Cooper EB, Scherder EJ, Cooper JB: Electrical treatment of reduced consciousness: experience with coma and Alzheimer’s disease. Neuropsychol Rehabil 2005;15:389–405.
  24. Schiff ND, Giacino JT, Kalmar K, Victor JD, Baker K, Gerber M, Fritz B, Eisenberg B, Biondi T, O’Connor J, Kobylarz EJ, Farris S, Machado A, McCagg C, Plum F, Fins JJ, Rezai AR: Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature 2007;448:600–603.
  25. Canavero S, Massa-Micon B, Cauda F, Montanaro E: Bifocal extradural cortical stimulation-induced recovery of consciousness in the permanent post-traumatic vegetative state. J Neurol 2009;256:834–836.
  26. Sara M, Pistoia F, Mura E, Onorati P, Govoni S: Intrathecal baclofen in patients with persistent vegetative state: 2 hypotheses. Arch Phys Med Rehabil 2009;90:1245–1249.
  27. Matsuda W, Sugimoto K, Sato N, Watanabe T, Yanaka K, Matsumura A, Nose T: A case of primary brainstem injury recovered from persistent vegetative state after L-DOPA administration (in Japanese). No To Shinkei 1999;51:1071–1074.
  28. Giacino JT, Kalmar K, Whyte J: The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil 2004;85:2020–2029.
  29. Hagan C, Malkmus D, Durham P: Levels of cognitive function; in Professional Staff Association (eds): Rehabilitation of the Head-Injured Adult. Comprehensive Physical Management. Downey, Rancho Los Amigos Hospital, 1979.
  30. Canavero S: Textbook of therapeutic cortical stimulation. Hauppauge, Nova Science, 2009.
  31. Canavero S, Bonicalzi V, Intonti S, Crasto S, Castellano G: Effects of bilateral extradural cortical stimulation for plegic stroke rehabilitation: case report. Neuromodulation 2006;9:28–33.

    External Resources

  32. Higashi K, Sakata Y, Hatano M, Abiko S, Ihara K, Katayama S, Wakuta Y, Okamura T, Ueda H, Zenke M, Aoki H: Epidemiological studies on patients with a persistent vegetative state. J Neurol Neurosurg Psychiatry 1977;40:876–885.
  33. Schiff ND: DBS disorders of consciousness; in Lozano AM, Gildenberg PL, Tasker RR (eds): Textbook of Stereotactic and Functional Neurosurgery, ed 2. Berlin, Springer, 2009, pp 2981–2990.
  34. McLardy T, Ervin F, Mark V, Scoville W, Sweet W: Attempted inset-electrodes-arousal from traumatic coma: neuropathological findings. Trans Am Neurol Assoc 1968;93:25–30.
  35. Hassler R, Ore GD, Dieckmann G, Bricolo A, Dolce G: Behavioural and EEG arousal induced by stimulation of unspecific projection systems in a patient with post-traumatic apallic syndrome. Electroencephalogr Clin Neurophysiol 1969;27:306–310.
  36. Hassler R, Ore GD, Bricolo A, Dieckmann G, Dolce G: EEG and clinical arousal induced by bilateral long-term stimulation of pallidal systems in traumatic vigil coma. Electroencephalogr Clin Neurophysiol 1969;27:689–690.
  37. Sturm V, Kühner A, Schmitt HP, Assmus H, Stock G: Chronic electrical stimulation of the thalamic-unspecific activating system in a patient with coma due to midbrain and upper brain stem infarction. Acta Neurochir (Wien) 1979;47:235–244.
  38. Tsubokawa T, Yamamoto T, Katayama Y, Hirayama T, Maejima S, Moriya T: Deep-brain stimulation in a persistent vegetative state: follow-up results and criteria for selection of candidates. Brain Inj 1990;4:315–327.
  39. Cohadon F, Richer E: Deep cerebral stimulation in patients with post-traumatic vegetative state: 25 cases (in French). Neurochirurgie 1993;39:281–292.
  40. Zafonte RD, Watanabe T, Mann NR: Amantadine: a potential treatment for the minimally conscious state. Brain Inj 1998;12:617–621.
  41. Clauss RP, Nel WH: Effect of zolpidem on brain injury and diaschisis as detected by 99mTc HMPAO brain SPECT in humans. Arzneimittelforschung 2004;54:641–646.
  42. Clauss RP, Güldenpfennig WM, Nel HW, Sathekge MM, Venkannagari RR: Extraordinary arousal from semi-comatose state on zolpidem: a case report. S Afr Med J 2000;90:68–72.
  43. Clauss RP, Dormehl IC, Kilian E, Louw WK, Nel WH, Oliver DW: Cerebral blood perfusion after treatment with zolpidem and flumazenil in the baboon. Arzneimittelforschung 2002;52:740–744.
  44. Cohen L, Chaaban B, Habert MO: Transient improvement of aphasia with zolpidem. N Engl J Med 2004;350:949–950.
  45. Schiff ND: Central thalamic deep-brain stimulation in the severely injured brain: rationale and proposed mechanisms of action. Ann NY Acad Sci 2009;1157:101–116.
  46. Schiff ND, Fins JJ: Deep brain stimulation and cognition: moving from animal to patient. Curr Opin Neurol 2007;20:638–642.
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