Abstract
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.
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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 124:45–55
Hayashi H, Kato S (1989) Total manifestations of amyotrophic lateral sclerosis. J Neurol Sci 93:19–35
Hayashi H, Kato S, Kawada A (1991) Amyotrophic lateral sclerosis patients living beyond respiratory failure. J Neurol Sci 105:73–78
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 127–138
Ohno T, Shimizu T, Kato S, Hayashi H, Hirai S (2001) Effect of tamsulosin hydrochloride on sympathetic hyperactivity in amyotrophic lateral sclerosis. Auton Neurosci 88:94–98
Baltadzhieva R, Gurevich T, Korczyn AD (2005) Autonomic impairment in amyotrophic lateral sclerosis. Curr Opin Neurol 18:487–493
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 254:78–83
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 22:22–31
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 28:1625–1636
Sisson JC, Bolgos G, Johnson J (1991) Measuring acute changes in adrenergic nerve activity of the heart in the living animal. Am Heart J 121:1119–1123
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 155:60–67
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 53:1020–1025
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):96–107
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 169:13–21
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 66:265–267
Ziegler MG, Lake CR, Wood JH (1980) Relationship between cerebrospinal fluid norepinephrine and blood pressure in neurogenic patients. Clin Exp Hypretens 2:995–1008
Sachs C, Conradi S, Kajiser L (1985) Autonomic function in amyotrophic lateral sclerosis: a study of cardiovascular responses. Acta Neurol Scand 71:373–378
Litchy WJ, Low PA, Daube JR, Windebank AJ (1987) Autonomic abnormalities in amyotrophic lateral sclerosis. Neurology 37(Suppl I):162
Chida K, Sakamaki S, Takasu T (1989) Alteration in autonomic function and cardiovascular regulation in amyotrophic lateral sclerosis. J Neurol 236:127–130
Nogùes MA, Stalberg EV (1989) Autonomic analysis of heart rate variation: II. Findings in patients attending an EMG laboratory. Muscle Nerve 12:1001–1008
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)
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 134:57–60
Low PA, McLeod JG (1993) The autonomic neuropathies. In: Low PA (ed) Clinical autonomic disorders: evaluation and management. Little Brown, Boston, pp 395–421
Brownell B, Oppenheimer DR, Hughes JT (1970) The central nervous system in motor neurone disease. J Neurol Neurosurg Psychiatry 33:338–357
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 48:1103–1106
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 73:193–204
Takahashi H, Oyanagi K, Ikuta F (1993) The intermediolateral nucleus in sporadic amyotrophic lateral sclerosis. Acta Neuropathol (Berl) 86:190–192
Benarroch EE (1993) The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc 68:988–1001
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 502:296–305
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 45:1121–1127
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 12:323–331
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 23:756–761
Yoshita M, Hayashi M, Hirai S (1998) Decreased myocardial accumulation of 123I-meta-iodobenzyl guanidine in Parkinson’s disease. Nucl Med Commun 19:137–142
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 97:303–306
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 97:307–314
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 40:371–375
Orimo S, Ozawa E, Nakade S, Sugimato T, Mizusawa H (1999) (123)I- metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 67:189–194
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 41:71–77
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 27:566–573
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 74:423–426
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 57:1140–1141
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 73:776–777
Amino T, Orimo S, Itoh Y, Takahashi A, Uchihara T, Mizusawa H (2005) Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathol 15:29–34
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 109:583–588
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 99:308–314
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 51:579–584
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Tanaka, Y., Yamada, M., Koumura, A. et al. Cardiac sympathetic function in the patients with amyotrophic lateral sclerosis: analysis using cardiac [123I] MIBG scintigraphy. J Neurol 260, 2380–2386 (2013). https://doi.org/10.1007/s00415-013-7005-0
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DOI: https://doi.org/10.1007/s00415-013-7005-0