Journal of Neurology

, Volume 260, Issue 9, pp 2380–2386 | Cite as

Cardiac sympathetic function in the patients with amyotrophic lateral sclerosis: analysis using cardiac [123I] MIBG scintigraphy

  • Yuji Tanaka
  • Megumi Yamada
  • Akihiro Koumura
  • Takeo Sakurai
  • Yuichi Hayashi
  • Akio Kimura
  • Isao Hozumi
  • Takashi Inuzuka
Original Communication


Amyotrophic lateral sclerosis (ALS), which is the most serious form of degenerative motor neuron disease in adults, is characterized by upper and lower motor neuron degeneration, skeletal muscle atrophy, paralysis, and death. Some patients with respiratory-dependent ALS die of sudden cardiac arrest or anoxic encephalopathy following circulatory collapse, which may be associated with sympathetic hyperactivity. Cardiac [123I] MIBG scintigraphy is a diagnostic method of cardiac sympathetic function. However, few reports have addressed cardiac sympathetic function in ALS patients using this technique. We investigated cardiac sympathetic function in 63 ALS patients and 10 healthy volunteers using cardiac [123I] metaiodobenzylguanidine (MIBG) scintigraphy [heart/mediastinum ratio (H/M ratio) in the early phase and washout ratio (WR)] at the time of diagnosis. The WR of cardiac [123I] MIBG scintigraphy, which indicates cardiac sympathetic activity, was significantly increased in ALS patients compared with controls. ALS patients with an increased WR exhibited a significantly higher progression rate compared with those with normal WR. Moreover, the survival of ALS patients with increased WR was significantly decreased compared with those with normal WR. These results suggested that some patients with ALS have sympathetic hyperactivity at the time of diagnosis. ALS patients may suffer from chronic cardiac sympathetic hyperactivity, which is associated with sudden cardiac death and stress induced cardiomyopathy. Increased WR in cardiac [123I] MIBG scintigraphy may be a predictive factor in ALS patients.


Amyotrophic lateral sclerosis Cardiac sympathetic function Cardiac sympathetic hyperactivity [123I]-Metaiodobenzylguanidine (MIBG) scintigraphy 


Conflicts of interest

The authors state that they have no conflicts of interest.


  1. 1.
    Shimizu T, Hayashi H, Kato S, Hayashi M, Tanabe H, Oda M (1994) Circulatory collapse and sudden death in respirator-dependent amyotrophic lateral sclerosis. J Neurol Sci 124:45–55PubMedCrossRefGoogle Scholar
  2. 2.
    Hayashi H, Kato S (1989) Total manifestations of amyotrophic lateral sclerosis. J Neurol Sci 93:19–35PubMedCrossRefGoogle Scholar
  3. 3.
    Hayashi H, Kato S, Kawada A (1991) Amyotrophic lateral sclerosis patients living beyond respiratory failure. J Neurol Sci 105:73–78PubMedCrossRefGoogle Scholar
  4. 4.
    Hayashi H (1994) Long-term in-hospital ventilatory care for patients with ALS. In: Mitsumoto H, Norris FH (eds) Amyotrophic lateral sclerosis: a comprehensive guide to management. Demos publications, New York, pp 127–138Google Scholar
  5. 5.
    Ohno T, Shimizu T, Kato S, Hayashi H, Hirai S (2001) Effect of tamsulosin hydrochloride on sympathetic hyperactivity in amyotrophic lateral sclerosis. Auton Neurosci 88:94–98PubMedCrossRefGoogle Scholar
  6. 6.
    Baltadzhieva R, Gurevich T, Korczyn AD (2005) Autonomic impairment in amyotrophic lateral sclerosis. Curr Opin Neurol 18:487–493PubMedCrossRefGoogle Scholar
  7. 7.
    Asai H, Hirano M, Udaka F, Shimada K, Oda M, Kubori T, Nishinaka K, Tsujimura T, Izumi Y, Konishi N, Matsumoto S, Kameyama M, Ueno S (2007) Sympathetic disturbance increase risk of sudden cardiac arrest in sporadic ALS. J Neurol Sci 254:78–83PubMedCrossRefGoogle Scholar
  8. 8.
    Wieland DM, Brown LE, Rogers WL, Worthington KC, Wu JL, Clinthorne NH, Otto CA, Swanson DP, Beierwaltes WH (1981) Myocardial imaging with a radioiodinated norepinephrine storage analog. J Nucl Med 22:22–31PubMedGoogle Scholar
  9. 9.
    Sisson JC, Shapiro B, Meyers L, Mallete S, Mangner TJ, Wieland DM, Glowniak JV, Sherman P, Beierwaltes WH (1987) Metaiodobenzyl-guanidine to map scintigraphically the adrenergic nervous system in man. J Nucl Med 28:1625–1636PubMedGoogle Scholar
  10. 10.
    Sisson JC, Bolgos G, Johnson J (1991) Measuring acute changes in adrenergic nerve activity of the heart in the living animal. Am Heart J 121:1119–1123PubMedCrossRefGoogle Scholar
  11. 11.
    Yoshita M (1998) Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 155:60–67PubMedCrossRefGoogle Scholar
  12. 12.
    Braune S, Reinhardt M, Schnitzer R, Riedel A, Lücking CH (1999) Cardiac uptake of [123I] MIBG separates Parkinson’s disease from multiple system atrophy. Neurology 53:1020–1025PubMedCrossRefGoogle Scholar
  13. 13.
    Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on motor neuron diseases/amyotrophic lateral sclerosis of the world federation of neurology research group on neuromuscular diseases and the El Escorial “clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 124(Suppl):96–107PubMedCrossRefGoogle Scholar
  14. 14.
    Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS study group (Phase III). J Neurol Sci 169:13–21PubMedCrossRefGoogle Scholar
  15. 15.
    Kimura F, Fujimura C, Ishida S, Nakajima H, Furutama D, Uehara H, Shinoda K, Sugino M, Hanafusa T (2006) Progression rate of ALDFRS-R at time of diagnosis predicts survival time in ALS. Neurology 66:265–267PubMedCrossRefGoogle Scholar
  16. 16.
    Ziegler MG, Lake CR, Wood JH (1980) Relationship between cerebrospinal fluid norepinephrine and blood pressure in neurogenic patients. Clin Exp Hypretens 2:995–1008CrossRefGoogle Scholar
  17. 17.
    Sachs C, Conradi S, Kajiser L (1985) Autonomic function in amyotrophic lateral sclerosis: a study of cardiovascular responses. Acta Neurol Scand 71:373–378PubMedCrossRefGoogle Scholar
  18. 18.
    Litchy WJ, Low PA, Daube JR, Windebank AJ (1987) Autonomic abnormalities in amyotrophic lateral sclerosis. Neurology 37(Suppl I):162Google Scholar
  19. 19.
    Chida K, Sakamaki S, Takasu T (1989) Alteration in autonomic function and cardiovascular regulation in amyotrophic lateral sclerosis. J Neurol 236:127–130PubMedCrossRefGoogle Scholar
  20. 20.
    Nogùes MA, Stalberg EV (1989) Autonomic analysis of heart rate variation: II. Findings in patients attending an EMG laboratory. Muscle Nerve 12:1001–1008PubMedCrossRefGoogle Scholar
  21. 21.
    Tamura N, Shimazu K, Yamamoto T, Watanabe S, Onoda A, Itokawa K, Hamaguchi K (1991) A supplementary study of sympathetic nervous hypertension in motor neuron disease. Auton Nerv Syst 28:357–363 (in Japanese, abstract in English)Google Scholar
  22. 22.
    Shindo K, Tsunoda S, Shiozawa Z (1995) Increased sympathetic outflow to muscles in patients with amyotrophic lateral sclerosis: a comparison with other neuromuscular patients. J Neurol Sci 134:57–60PubMedCrossRefGoogle Scholar
  23. 23.
    Low PA, McLeod JG (1993) The autonomic neuropathies. In: Low PA (ed) Clinical autonomic disorders: evaluation and management. Little Brown, Boston, pp 395–421Google Scholar
  24. 24.
    Brownell B, Oppenheimer DR, Hughes JT (1970) The central nervous system in motor neurone disease. J Neurol Neurosurg Psychiatry 33:338–357PubMedCrossRefGoogle Scholar
  25. 25.
    Kennedy PG, Duchen LW (1985) A quantitative study of intermediolateral column cells in motor neuron disease and the Shy-Drager syndrome. J Neurol Neurosurg Psychiatry 48:1103–1106PubMedCrossRefGoogle Scholar
  26. 26.
    Konno H, Yamamoto T, Iwasaki Y, Iizuka H (1986) Shy-Drager syndrome and amyotrophic lateral sclerosis. Cytoarchitectonic and morphometric studies of sacral autonomic neurons. J Neurol Sci 73:193–204PubMedCrossRefGoogle Scholar
  27. 27.
    Takahashi H, Oyanagi K, Ikuta F (1993) The intermediolateral nucleus in sporadic amyotrophic lateral sclerosis. Acta Neuropathol (Berl) 86:190–192CrossRefGoogle Scholar
  28. 28.
    Benarroch EE (1993) The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc 68:988–1001PubMedCrossRefGoogle Scholar
  29. 29.
    Cechetto DF, Wilson JX, Smith KE, Wolski D, Silver MD, Hachinski VC (1989) Autonomic and myocardial changes in middle cerebral artery occlusion: stroke models in the rat. Brain Res 502:296–305PubMedCrossRefGoogle Scholar
  30. 30.
    Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Musha H, Sasaka K (2004) 123I-MIBG myocardial scintigraphy in patients with “takotsubo” cardiomyopathy. J Nucl Med 45:1121–1127PubMedGoogle Scholar
  31. 31.
    Nagamachi S, Jinnouchi S, Kurose T, Ohnishi T, Flores LG 2nd, Nakahara H, Futami S, Tamura S, Matsukura S (1998) 123I-MIBG myocardial scintigraphy in diabetic patients: relationship with 201Tl uptake and cardiac autonomic function. Ann Nucl Med 12:323–331PubMedCrossRefGoogle Scholar
  32. 32.
    Morimoto S, Terada K, Keira N, Satoda M, Inoue K, Tatsukawa H, Katoh S, Ida K, Sugihara H, Takeda K, Nakagawa M (1996) Investigation of the relationship between regression of hypertensive cardiac hypertrophy and improvement of cardiac sympathetic nervous dysfunction using iodine-123 metaiodobenzylguanidine myocardial imaging. Eur J Nucl Med 23:756–761PubMedCrossRefGoogle Scholar
  33. 33.
    Yoshita M, Hayashi M, Hirai S (1998) Decreased myocardial accumulation of 123I-meta-iodobenzyl guanidine in Parkinson’s disease. Nucl Med Commun 19:137–142PubMedCrossRefGoogle Scholar
  34. 34.
    Iwasa K, Nakajima K, Yoshikawa H, Tada A, Taki J, Takamori M (1998) Decreased myocardial 123I-MIBG uptake in Parkinson’s disease. Acta Neurol Scand 97:303–306PubMedCrossRefGoogle Scholar
  35. 35.
    Braune S, Reinhardt M, Bathmann J, Krause T, Lehmann M, Lucking CH (1998) Impaired cardiac uptake of meta- [123 I] iodobenzylguanidine in Parkinson’s disease with autonomic failure. Acta Neurol Scand 97:307–314PubMedCrossRefGoogle Scholar
  36. 36.
    Satoh A, Serita T, Seto M, Tomita I, Satoh H, Iwanaga K, Takahashi H, Tsujihata M (1999) Loss of 123I-MIBG uptake by the heart in Parkinson’s disease: assessment of cardiac sympathetic denervation and diagnostic value. J Nucl Med 40:371–375PubMedGoogle Scholar
  37. 37.
    Orimo S, Ozawa E, Nakade S, Sugimato T, Mizusawa H (1999) (123)I- metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 67:189–194PubMedCrossRefGoogle Scholar
  38. 38.
    Takatsu H, Nishida H, Matsuo H, Watanabe S, Nagashima K, Wada H, Noda T, Nishigaki K, Fujiwara H (2000) Cardiac sympathetic denervation from the early stage of Parkinson’s disease: clinical and experimental studies with radiolabeled MIBG. J Nucl Med 41:71–77PubMedGoogle Scholar
  39. 39.
    Taki J, Nakajima K, Hwang EH, Matsunari I, Komai K, Yoshita M, Sakajiri K, Tonami N (2000) Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific. Eur J Nucl Med 27:566–573PubMedCrossRefGoogle Scholar
  40. 40.
    Hamada K, Hirayama M, Watanabe H, Kobayashi R, Ito H, Ieda T, Koike Y, Sobue G (2003) Onset age and severity of motor impairment are associated with reduction of myocardial 123I-MIBG uptake in Parkinson’s disease. J Neurol Neurosurg Psychiatry 74:423–426PubMedCrossRefGoogle Scholar
  41. 41.
    Orimo S, Ozawa E, Oka T, Nakade S, Tsuchiya K, Yoshimoto M, Wakabayashi K, Takahashi H (2001) Different histopathology accounting for a decrease in myocardial MIBG uptake in PD and MSA. Neurology 57:1140–1141PubMedCrossRefGoogle Scholar
  42. 42.
    Orimo S, Oka T, Miura H, Tsuchiya K, Mori F, Wakabayashi K, Nagao T, Yokochi M (2002) Sympathetic cardiac denervation in Parkinson’s disease and pure autonomic failure but not in multiple system atrophy. J Neurol Neurosurg Psychiatry 73:776–777PubMedCrossRefGoogle Scholar
  43. 43.
    Amino T, Orimo S, Itoh Y, Takahashi A, Uchihara T, Mizusawa H (2005) Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathol 15:29–34PubMedCrossRefGoogle Scholar
  44. 44.
    Orimo S, Amino T, Itoh Y, Takahashi A, Kojo T, Uchihara T, Tsuchiya K, Mori F, Wakabayashi K, Takahashi H (2005) Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol 109:583–588PubMedCrossRefGoogle Scholar
  45. 45.
    Druschky A, Spitzer A, Platsch G, Claus D, Feistel H, Druschky K, Hilz MJ, Neundorfer B (1999) Cardiac sympathetic denervation in early stages of amyotrophic lateral sclerosis demonstrated by 123I-MIBG-SPECT. Acta Neurol Scand 99:308–314PubMedCrossRefGoogle Scholar
  46. 46.
    Tanaka Y, Yoshikura N, Harada N, Yamada M, Koumura A, Sakurai T, Hayashi Y, Kimura A, Hozumi I, Inuzuka T (2012) Late-onset patients with sporadic amyotrophic lateral sclerosis in Japan have a higher progression rate of ALSFRS-R at the time of diagnosis. Intern Med 51:579–584PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Yuji Tanaka
    • 1
  • Megumi Yamada
    • 1
  • Akihiro Koumura
    • 1
  • Takeo Sakurai
    • 1
  • Yuichi Hayashi
    • 1
  • Akio Kimura
    • 1
  • Isao Hozumi
    • 1
  • Takashi Inuzuka
    • 1
  1. 1.Department of Neurology and Geriatrics, Graduate School of MedicineGifu UniversityGifuJapan

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