Neurological Surgery 脳神経外科36巻7号

2008年07月発行

総説

バクロフェン髄注療法

著者： 平孝臣¹ 堀智勝¹

所属機関： ¹東京女子医科大学脳神経外科

ページ範囲：P.573 - P.590

Ⅰ．はじめに

　バクロフェン髄注療法（intrathecal baclofen therapy：ITB）は，その他の治療で十分にコントロールできない重症の痙縮の治療として，本邦では2006年に導入され，2年が経過しようとしている．一方諸外国では，これまでに5万人程度がこの治療を受け，すでにリハビリテーション医学や脳神経外科，神経内科領域でも一般的医療として定着している．本稿ではITBについて，その歴史的背景を含めながら，適応，手術手技，効果や合併症などについて説明するとともに，今後の展望についても触れたい．

参考文献

1）Albanese A, Barnes MP, Bhatia KP, Fernandez-Alvarez E, Filippini G, Gasser T, Krauss JK, Newton A, Rektor I, Savoiardo M, Valls-Sole J：A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes：report of an EFNS/MDS-ES Task Force. Eur J Neurol 13：433-444, 2006

2）Albright AL：Neurosurgical treatment of spasticity and other pediatric movement disorders. J Child Neurol 18 Suppl 1：S67-78, 2003

3）Albright AL：Intraventricular baclofen infusion for dystonia. Report of two cases. J Neurosurg 105：71-74, 2006

4）Albright AL, Barry MJ, Fasick MP, Janosky J：Effects of continuous intrathecal baclofen infusion and selective posterior rhizotomy on upper extremity spasticity. Pediatr Neurosurg 23：82-85, 1995

5）Albright AL, Barry MJ, Fasick P, Barron W, Shultz B：Continuous intrathecal baclofen infusion for symptomatic generalized dystonia. Neurosurgery 38：934-938；discussion 938-939, 1996

6）Albright AL, Barry MJ, Painter MJ, Shultz B：Infusion of intrathecal baclofen for generalized dystonia in cerebral palsy. J Neurosurg 88：73-76, 1998

7）Albright AL, Barry MJ, Shafton DH, Ferson SS：Intrathecal baclofen for generalized dystonia. Dev Med Child Neurol 43：652-657, 2001

8）Albright AL, Gilmartin R, Swift D, Krach LE, Ivanhoe CB, McLaughlin JF：Long-term intrathecal baclofen therapy for severe spasticity of cerebral origin. J Neurosurg 98：291-295, 2003

9）Albright AL, Turner M, Pattisapu JV：Best-practice surgical techniques for intrathecal baclofen therapy. J Neurosurg 104：233-239, 2006

10）Armstrong RW：The first meta-analysis of randomized controlled surgical trials in cerebral palsy (2002). Dev Med Child Neurol 50：244, 2008

11）Bardutzky J, Tronnier V, Schwab S, Meinck HM：Intrathecal baclofen for stiff-person syndrome：life-threatening intermittent catheter leakage. Neurology 60：1976-1978, 2003

12）Becker R, Alberti O, Bauer BL：Continuous intrathecal baclofen infusion in severe spasticity after traumatic or hypoxic brain injury. J Neurol 244：160-166, 1997

13）Becker R, Sure U, Petermeyer M, Bertalanffy H：Continuous intrathecal baclofen infusion alleviates autonomic dysfunction in patients with severe supraspinal spasticity. J Neurol Neurosurg Psychiatry 66：114, 1999

14）Becker WJ, Ablett DP, Harris CJ, Dold ON：Long term treatment of intractable reflex sympathetic dystrophy with intrathecal morphine. Can J Neurol Sci 22：153-159, 1995

15）Bhatia KP, Bhatt MH, Marsden CD：The causalgia-dystonia syndrome. Brain 116 Pt 4：843-851, 1993

16）Bischoff W：Die longitudinale Myelotomie. Zentralbl Neurochir 11：79-88, 1951

17）Bohannon R, Smith M：Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 67：206-207, 1987

18）Boots RJ, Lipman J, O’Callaghan J, Scott P, Fraser J：The treatment of tetanus with intrathecal baclofen. Anaesth Intensive Care 28：438-442, 2000

19）Buffenoir K, Roujeau T, Lapierre F, Menei P, Menegalli-Boggelli D, Mertens P, Decq P：Spastic equinus foot：multicenter study of the long-term results of tibial neurotomy. Neurosurgery 55：1130-1137, 2004

20）Coffey JR, Cahill D, Steers W, Park TS, Ordia J, Meythaler J, Herman R, Shetter AG, Levy R, Gill B, et al.：Intrathecal baclofen for intractable spasticity of spinal origin：results of a long-term multicenter study. J Neurosurg 78：226-232, 1993

21）Coffey RJ, Burchiel K：Inflammatory mass lesions associated with intrathecal drug infusion catheters：report and observations on 41 patients. Neurosurgery 50：78-86；discussion 86-77, 2002

22）Cooper IS：Neurosurgical treatment of dystonia. Neurology 20：133-148, 1970

23）Cooper IS, Amin I, Upton A, Riklan M, Watkins S, McLellan L：Safety and efficacy of chronic stimulation. Neurosurgery 1：203-205, 1977

24）Cooper IS, Hoen TI, Poloukhine N：Chemopallidectomy for dystonia musculorum deformans. J Am Geriatr Soc 4：1208-1213, 1956

25）Cooper IS, Riklan M, Amin I, Waltz JM, Cullinan T：Chronic cerebellar stimulation in cerebral palsy. Neurology 26：744-753, 1976

26）Cooper IS, Riklan M, Badell A, Laszewski Z：Dystonia musculorum deformans：neurosurgical treatment, rehabilitation and follow-up. Arch Phys Med Rehabil 43：607-614, 1962

27）Cruikshank M, Eunson P：Intravenous diazepam infusion in the management of planned intrathecal baclofen withdrawal. Dev Med Child Neurol 49：626-628, 2007

28）Cui JG, Meyerson BA, Sollevi A, Linderoth B：Effect of spinal cord stimulation on tactile hypersensitivity in mononeuropathic rats is potentiated by simultaneous GABA(B) and adenosine receptor activation. Neurosci Lett 247：183-186, 1998

29）Darbari FP, Melvin JJ, Piatt JH, Jr., Adirim TA, Kothare SV：Intrathecal baclofen overdose followed by withdrawal：clinical and EEG features. Pediatr Neurol 33：373-377, 2005

30）Dario A, Tomei G：Management of spasticity in multiple sclerosis by intrathecal baclofen. Acta Neurochir Suppl 97：189-192, 2007

31）Deer TR, Raso LJ, Garten TG：Inflammatory mass of an intrathecal catheter in patients receiving baclofen as a sole agent：a report of two cases and a review of the identification and treatment of the complication. Pain Med 8：259-262, 2007

32）Duhon BS, MacDonald JD：Infusion of intrathecal baclofen for acute withdrawal. Technical note. J Neurosurg 107：878-880, 2007

33）Engrand N, Guerot E, Rouamba A, Vilain G：The efficacy of intrathecal baclofen in severe tetanus. Anesthesiology 90：1773-1776, 1999

34）Ford B, Greene P, Louis ED, Petzinger G, Bressman SB, Goodman R, Brin MF, Sadiq S, Fahn S：Use of intrathecal baclofen in the treatment of patients with dystonia. Arch Neurol 53：1241-1246, 1996

35）Francisco GE, Hu MM, Boake C, Ivanhoe CB：Efficacy of early use of intrathecal baclofen therapy for treating spastic hypertonia due to acquired brain injury. Brain Inj 19：359-364, 2005

36）Francisco GE, Latorre JM, Ivanhoe CB：Intrathecal baclofen therapy for spastic hypertonia in chronic traumatic brain injury. Brain Inj 21：335-338, 2007

37）Francisco GE, Yablon SA, Schiess MC, Wiggs L, Cavalier S, Grissom S：Consensus panel guidelines for the use of intrathecal baclofen therapy in poststroke spastic hypertonia. Top Stroke Rehabil 13：74-85, 2006

38）Francois B, Vacher P, Roustan J, Salle JY, Vidal J, Moreau JJ, Vignon P：Intrathecal baclofen after traumatic brain injury：early treatment using a new technique to prevent spasticity. J Trauma 50：158-161, 2001

39）福内明子，岩出宗代，尾崎恭子，曽根依子，鈴木英弘，平　孝臣：脊柱管狭窄症患者の末梢循環障害に対するバクロフェン髄腔内投与の効果．ペインクリニック 21：81-85, 2000

40）Gooch JL, Oberg WA, Grams B, Ward LA, Walker ML：Care provider assessment of intrathecal baclofen in children. Dev Med Child Neurol 46：548-552, 2004

41）後藤真一，平　孝臣：2．痙性麻痺の新しい治療．pp276-280（柳澤信夫，篠原幸人，岩田　誠，清水輝夫，寺本　明 編：Annual Review神経2008. ⅩⅢ. 脊髄疾患，中外科学社，東京，2008）

42）後藤真一，平　孝臣，落合　卓，田中雅彦，加藤宏一，佐々木寿之，石井　暁，堀　智勝：髄腔内バクロフェンポンプ（ITB）治療における痙縮と至適投与量に関する検討．機能的脳神経外科46：144-148, 2007

43）Hansen CR, Gooch JL, Such-Neibar T：Prolonged, severe intrathecal baclofen withdrawal syndrome：a case report. Arch Phys Med Rehabil 88：1468-1471, 2007

44）Herman RM, D’Luzansky SC, Ippolito R：Intrathecal baclofen suppresses central pain in patients with spinal lesions. A pilot study. Clin J Pain 8：338-345, 1992

45）Horn TS, Yablon SA, Stokic DS：Effect of intrathecal baclofen bolus injection on temporospatial gait characteristics in patients with acquired brain injury. Arch Phys Med Rehabil 86：1127-1133, 2005

46）Jaffe MS, Nienstedt LJ：Intrathecal baclofen for generalized dystonia：a case report. Arch Phys Med Rehabil 82：853-855, 2001

47）Jang SH, Park SM, Kim SH, Ahn SH, Cho YW, Ahn MO：The effect of selective tibial neurotomy and rehabilitation in a quadriplegic patient with ankle spasticity following traumatic brain injury. Yonsei Med J 45：743-747, 2004

48）Kan P, Gooch J, Amini A, Ploeger D, Grams B, Oberg W, Simonsen S, Walker M, Kestle J：Surgical treatment of spasticity in children：comparison of selective dorsal rhizotomy and intrathecal baclofen pump implantation. Childs Nerv Syst 24：239-243, 2008

49）Kao LW, Amin Y, Kirk MA, Turner MS：Intrathecal baclofen withdrawal mimicking sepsis. J Emerg Med 24：423-427, 2003

50）Kawecki Z, Kwiatkowski S, Grzegorzewski P, Szlachta Jezioro I：[Sudden improvement of all neurological functions after general anesthesia and two-day intrathecal infusion of baclofen in a child with primary brain-stem injury]. Przegl Lek 64 Suppl 2：13-14, 2007

51）Korenkov AI, Niendorf WR, Darwish N, Glaeser E, Gaab MR：Continuous intrathecal infusion of baclofen in patients with spasticity caused by spinal cord injuries. Neurosurg Rev 25：228-230, 2002

52）Kroin JS, Ali A, York M, Penn RD：The distribution of medication along the spinal canal after chronic intrathecal administration. Neurosurgery 33：226-230；discussion 230, 1993

53）Kroin JS, Bianchi GD, Penn RD：Intrathecal baclofen down-regulates GABAB receptors in the rat substantia gelatinosa. J Neurosurg 79：544-549, 1993

54）Kroin JS, Penn RD, Beissinger RL, Arzbaecher RC：Reduced spinal reflexes following intrathecal baclofen in the rabbit. Exp Brain Res 54：191-194, 1984

55）Langerak NG, Lamberts RP, Fieggen AG, Peter JC, van der Merwe L, Peacock WJ, Vaughan CL：A prospective gait analysis study in patients with diplegic cerebral palsy 20 years after selective dorsal rhizotomy. J Neurosurg Pediatrics 1：180-186, 2008

56）Leung NY, Whyte IM, Isbister GK：Baclofen overdose：defining the spectrum of toxicity. Emerg Med Australas 18：77-82, 2006

57）Lind G, Meyerson BA, Winter J, Linderoth B：Intrathecal baclofen as adjuvant therapy to enhance the effect of spinal cord stimulation in neuropathic pain：a pilot study. Eur J Pain 8：377-383, 2004

58）Lind G, Schechtmann G, Winter J, Linderoth B：Drug-enhanced spinal stimulation for pain：a new strategy. Acta Neurochir Suppl 97：57-63, 2007

59）Lind G, Schechtmann G, Winter J, Meyerson BA, Linderoth B：Baclofen-enhanced spinal cord stimulation and intrathecal baclofen alone for neuropathic pain：long-term outcome of a pilot study. Eur J Pain 12：132-136, 2008

60）Loubser PG, Narayan RK, Sandin KJ, Donovan WH, Russell KD：Continuous infusion of intrathecal baclofen：long-term effects on spasticity in spinal cord injury. Paraplegia 29：48-64, 1991

61）Maarrawi J, Mertens P, Luaute J, Vial C, Chardonnet N, Cosson M, Sindou M：Long-term functional results of selective peripheral neurotomy for the treatment of spastic upper limb：prospective study in 31 patients. J Neurosurg 104：215-225, 2006

62）Meythaler JM, Steers WD, Tuel SM, Cross LL, Sesco DC, Haworth CS：Intrathecal baclofen in hereditary spastic paraparesis. Arch Phys Med Rehabil 73：794-797, 1992

63）Middleton JW, Siddall PJ, Walker S, Molloy AR, Rutkowski SB：Intrathecal clonidine and baclofen in the management of spasticity and neuropathic pain following spinal cord injury：a case study. Arch Phys Med Rehabil 77：824-826, 1996

64）Mohammed I, Hussain A：Intrathecal baclofen withdrawal syndrome- a life-threatening complication of baclofen pump：a case report. BMC Clin Pharmacol 4：6, 2004

65）Muller H, Borner U, Zierski J, Hempelmann G：Intrathecal baclofen for treatment of tetanus-induced spasticity. Anesthesiology 66：76-79, 1987

66）Munro D：Anterior rhizotomy for spastic paraplegia. N Engl J Med 233：453-461, 1922

67）Nance P, Schryvers O, Schmidt B, Dubo H, Loveridge B, Fewer D：Intrathecal baclofen therapy for adults with spinal spasticity：therapeutic efficacy and effect on hospital admissions. Can J Neurol Sci 22：22-29, 1995

68）Narayan RK, Loubser PG, Jankovic J, Donovan WH, Bontke CF：Intrathecal baclofen for intractable axial dystonia. Neurology 41：1141-1142, 1991

69）Ostermann ME, Young B, Sibbald WJ, Nicolle MW：Coma mimicking brain death following baclofen overdose. Intensive Care Med 26：1144-1146, 2000

70）Paret G, Tirosh R, Ben Zeev B, Vardi A, Brandt N, Barzilay Z：Intrathecal baclofen for severe torsion dystonia in a child. Acta Paediatr 85：635-637, 1996

71）Park TS, Johnston JM：Surgical techniques of selective dorsal rhizotomy for spastic cerebral palsy. Technical note. Neurosurg Focus 21：e7, 2006

72）Penn RD：Chronic cerebellar stimulation for cerebral palsy：a review. Neurosurgery 10：116-121, 1982

73）Penn RD, Gottlieb GL, Agarwal GC：Cerebellar stimulation in man. Quantitative changes in spasticity. J Neurosurg 48：779-786, 1978

74）Penn RD, Kroin JS：Intrathecal baclofen alleviates spinal cord spasticity. Lancet 1：1078, 1984

75）Penn RD, Kroin JS：Continuous intrathecal baclofen for severe spasticity. Lancet 2：125-127, 1985

76）Penn RD, Kroin JS：Long-term intrathecal baclofen infusion for treatment of spasticity. J Neurosurg 66：181-185, 1987

77）Penn RD, Mangieri EA：Stiff-man syndrome treated with intrathecal baclofen. Neurology 43：2412, 1993

78）Penn RD, Savoy SM, Corcos D, Latash M, Gottlieb G, Parke B, Kroin JS：Intrathecal baclofen for severe spinal spasticity. N Engl J Med 320：1517-1521, 1989

79）Rabinstein AA, Benarroch EE：Treatment of paroxysmal sympathetic hyperactivity. Curr Treat Options Neurol 10：151-157, 2008

80）Richard I, Menei P：Intrathecal baclofen in the treatment of spasticity, dystonia and vegetative disorders. Acta Neurochir Suppl 97：213-218, 2007

81）Ridley B：Intrathecal baclofen therapy：challenges in patients with multiple sclerosis. Rehabil Nurs 31：158-164, 2006

82）Romito LM, Franzini A, Perani D, Carella F, Marras C, Capus L, Garibotto V, Broggi G, Albanese A：Fixed dystonia unresponsive to pallidal stimulation improved by motor cortex stimulation. Neurology 68：875-876, 2007

83）Rosenow J, Das K, Rovit RL, Couldwell WT：Irving S. Cooper and his role in intracranial stimulation for movement disorders and epilepsy. Stereotact Funct Neurosurg 78：95-112, 2002

84）Sadiq SA, Poopatana CA：Intrathecal baclofen and morphine in multiple sclerosis patients with severe pain and spasticity. J Neurol 254：1464-1465, 2007

85）Santos ML, Mota-Miranda A, Alves-Pereira A, Gomes A, Correia J, Marcal N：Intrathecal baclofen for the treatment of tetanus. Clin Infect Dis 38：321-328, 2004

86）Sara M, Sacco S, Cipolla F, Onorati P, Scoppetta C, Albertini G, Carolei A：An unexpected recovery from permanent vegetative state. Brain Inj 21：101-103, 2007

87）Schrag A, Trimble M, Quinn N, Bhatia K：The syndrome of fixed dystonia：an evaluation of 103 patients. Brain 127：2360-2372, 2004

88）Shirley KW, Kothare S, Piatt JH Jr, Adirim TA：Intrathecal baclofen overdose and withdrawal. Pediatr Emerg Care 22：258-261, 2006

89）Siegfried J：Neurosurgical treatment of spasticity. pp123-128 (Rasmussen T, Marino R eds：Functional Neurosurgery. Raven Press, New York, 1979)

90）Silbert PL, Matsumoto JY, McManis PG, Stolp-Smith KA, Elliott BA, McEvoy KM：Intrathecal baclofen therapy in stiff-man syndrome：a double-blind, placebo-controlled trial. Neurology 45：1893-1897, 1995

91）Sindou MP, Simon F, Mertens P, Decq P：Selective peripheral neurotomy (SPN) for spasticity in childhood. Childs Nerv Syst 23：957-970, 2007

92）Slonimski M, Abram SE, Zuniga RE：Intrathecal baclofen in pain management. Reg Anesth Pain Med 29：269-276, 2004

93）Steinbok P：Selection of treatment modalities in children with spastic cerebral palsy. Neurosurg Focus 21：e4, 2006

94）Steinbok P：Selective dorsal rhizotomy for spastic cerebral palsy：a review. Childs Nerv Syst 23：981-990, 2007

95）Steinbok P, Daneshvar H, Evans D, Kestle JR：Cost analysis of continuous intrathecal baclofen versus selective functional posterior rhizotomy in the treatment of spastic quadriplegia associated with cerebral palsy. Pediatr Neurosurg 22：255-264；discussion 265, 1995

96）Taira T, Kawamura H, Tanikawa T, Kawabatake H, Iseki H, Ueda A, Imamura T, Nagai M, Takakura K：Dramatic recovery of consciousness after spinal intrathecal administration of baclofen in patients with severe head injury. Proc Soc Treatment of Coma 5：127-134, 1996

97）Taira T, Hori T：Intrathecal baclofen in the treatment of post-stroke central pain, dystonia, and persistent vegetative state. Acta Neurochir Suppl 97：227-229, 2007

98）Taira T, Kawamura H, Tanikawa T, Iseki H, Kawabatake H, Takakura K：A new approach to control central deafferentation pain：spinal intrathecal baclofen. Stereotact Funct Neurosurg 65：101-105, 1995

99）Taira T, Kawamura H, Tanikawa T, Kawabatake H, Iseki H, Ueda A, Takakura K：A new approach to the control of central deafferentation pain--spinal intrathecal baclofen. Acta Neurochir Suppl 64：136-138, 1995

100）Taira T, Ochiai T, Goto S, Hori T：Fifteen year experience of intrathecal baclofen treatment in Japan. Acta Neurochir 99 Suppl：61-63, 2006

101）Taira T, Tanikawa T, Kawamura H, Iseki H, Takakura K：Spinal intrathecal baclofen suppresses central pain after a stroke. J Neurol Neurosurg Psychiatry 57：381-382, 1994

102）平　孝臣：神経源性疼痛とバクロフェンの髄腔内投与．ペインクリニック17：865-872, 1996

103）平　孝臣：痙縮治療の新展開―バクロフェン髄注療法バクロフェン髄注療法の歴史．脳21 10：351-355, 2007

104）平　孝臣，河村弘庸，谷川達也，伊関　洋，川畠弘子，上田麻子，高倉公明：脊髄損傷後の中枢性疼痛に対する腰部髄腔内バクロフェン投与の効果．機能的脳神経外科33：45-49, 1995

105）平　孝臣，堀　智勝：脳性麻痺の痙縮の外科治療．No Shinkei Geka 29：1137-1150, 2001

106）Tilton AH：Management of spasticity in children with cerebral palsy. Semin Pediatr Neurol 11：58-65, 2004

107）Turner MS：Early use of intrathecal baclofen in brain injury in pediatric patients. Acta Neurochir Suppl 87：81-83, 2003

108）Van Hilten BJ, van de Beek WJ, Hoff JI, Voormolen JH, Delhaas EM：Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy. N Engl J Med 343：625-630, 2000

109）Vloeberghs M, Keetley R, Morton R：Intrathecal baclofen in the management of spasticity due to cerebral palsy. Pediatr Rehabil 8：172-179, 2005

110）Von Koch CS, Park TS, Steinbok P, Smyth M, Peacock WJ：Selective posterior rhizotomy and intrathecal baclofen for the treatment of spasticity. Pediatr Neurosurg 35：57-65, 2001

111）Woon K, Tsegaye M, Vloeberghs MH：The role of intrathecal baclofen in the management of primary and secondary dystonia in children. Br J Neurosurg 21：355-358, 2007

112）Young R：Spasticity：a review. Neurology 44 Suppl 9：S12-S20, 1994

113）Young RR, Delwaide PJ：Drug therapy：spasticity (first of two parts). N Engl J Med 304：28-33, 1981

114）Young RR, Delwaide PJ：Drug therapy：spasticity (second of two parts). N Engl J Med 304：96-99, 1981

115）Zuckerbraun NS, Ferson SS, Albright AL, Vogeley E：Intrathecal baclofen withdrawal：emergent recognition and management. Pediatr Emerg Care 20：759-764, 2004

116）Zuniga RE, Perera S, Abram SE：Intrathecal baclofen：a useful agent in the treatment of well-established complex regional pain syndrome. Reg Anesth Pain Med 27：90-93, 2002

117）Zuniga RE, Schlicht CR, Abram SE：Intrathecal baclofen is analgesic in patients with chronic pain. Anesthesiology 92：876-880, 2000