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• MIBG is useful, but not absolute, in clinical practice
  Hiroshi Nagayama
  Published on: 31 March 2005
• MIBG in clinical routine
  Stefan Braune
  Published on: 2 March 2005

• Published on: 31 March 2005

  MIBG is useful, but not absolute, in clinical practice

  • Hiroshi Nagayama
  • Other Contributors:
    • Makoto Hamamoto, Masayuki Ueda, Jun-ichi Nagashima and Yasuo Katayama

  Dear Editor,

  We are grateful to Dr. Braune for his comments regarding our recent paper [1], and appreciate the opportunity for further discussion. The most important thing in our paper was that MIBG scintigraphy was carried out in the largest number of parkinsonian patient-series to verify the usefulness of the examination in clinical routine. Since all of them were outpatients, only clinical diagnosis was av...

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  Dear Editor,

  We are grateful to Dr. Braune for his comments regarding our recent paper [1], and appreciate the opportunity for further discussion. The most important thing in our paper was that MIBG scintigraphy was carried out in the largest number of parkinsonian patient-series to verify the usefulness of the examination in clinical routine. Since all of them were outpatients, only clinical diagnosis was available for our patients.

  The normal lower limit of H/M ratio is important, since it may directly influence sensitivity and specificity for diagnosing Parkinson's disease [PD]. The cut-off level of 1.84, obtained from 10 normal volunteers in our study, was slightly high compared with that of 1.75 provided by the recent meta-analysis of six MIBG studies, based on 69 normal subjects [2]. Therefore we re-calculated the sensitivity and specificity for diagnosing PD using the cut off of 1.75 in our patient-series to confirm our first conclusion. Although the sensitivity (85.3%) remained high, the specificity (40.6%) was still considerably low despite re-calculation, suggesting that the low specificity described in the recent publication [1] did not result from high cut off value.

  Several disorders with Lewy bodies are reportedly related to low cardiac MIBG uptake [3-5]. Our patients with Alzheimer's disease (AD) showed surprisingly low MIBG uptake, conflicting with the previous observations [3-5]. Recent pathological study revealed that alpha-Synuclein lesions, including Lewy bodies, co-existed with AD pathology, and that these lesions were found in more than 30-40% of AD patients [6,7]. Furthermore incidental Lewy bodies are reportedly associated with age [8]. The AD patients in our study were characterized by one or more motor symptoms, and were relatively older (77.0 +/- 6.5 years) than those in the previous reports [3-5].

  Therefore, Lewy body pathology might exist more frequently in our AD patients compared with those in the previous observations [3-5], resulting in low H/M ratios. The H/M ratios in our patients suffering from dementia with Lewy bodies (DLB) were extremely low, consistent with the previous reports [3-5]. The diagnostic criterion for DLB in our study was based on the probable criterion of the Consortium on DLB [9]. The specificity of the criteria is reportedly high while its sensitivity is low [10]. Clinically, our DLB patients were, therefore, quite uniform, resulting in low MIBG uptake. Reduced MIBG uptake found in our patients with cerebrovascular disease is also interesting, although precise causative factors for the low uptake remains unclear. Since such patients might have several risks for vascular events, the low uptake might result from cryptic heart ischemia, which was not detectable using ECG, as well as incidental Lewy body pathology related to aging. Nothing but only post-mortem analysis can resolve these speculations.

  We believe our data probably match with the recent pathological knowledge regarding Lewy bodies. Our conclusion is that MIBG is useful, but not absolute, in clinical practice.

  References

  1. Nagayama H, Hamamoto M, Ueda M, et al. Reliability of MIBG myocardial scintigraphy in the diagnosis of Parkinson's disease. J Neurol Neurosurg Psychiatry 2005;76:249-51.

  2. Braune S. The role of cardiac metaiodobenzylguanidine in the differential diagnosis of parkinsonian syndromes. Clin Autonom Res 2001;11:351-355.

  3. Watanabe H, Ieda T, Katayama T et al. Cardiac (123)I- meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer's disease. J Neurol Neurosurg Psychiatry 2001;70:781- 783.

  4. Yoshita M, Taki J, Yamada M. A clinical role for [(123)I]MIBG myocardial scintigraphy in the distinction between dementia of the Alzheimer's-type and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2001;71:583-588.

  5. Oide T, Tokuda T, Momose M, et al. Usefulness of [123I]metaiodobenzylguanidine ([123I]MIBG) myocardial scintigraphy in differentiating between Alzheimer's disease and dementia with Lewy bodies. Intern Med 2003;42:686-690.

  6. Mikolaenko I, Pletnikova O, Kawas CH, et al. Alpha- synclein lesions in norlka aging, Parkinson disease, and Alzheimer disease: Evidence from the Baltimore longitudinal study of aging (BLSA). J Neuropahol Exp Neurol 2005;64:156- 62.

  7. Arai Y, Yamazaki M, Mori O, et al. Alfa-synuclein- positive structure in cases with sporadic AlzheimerÕs disease: morphology and its relationship to tau aggregation. Brain Res 2001;888:287-96.

  8. Saito Y, Ruberu NN, Sawabe M, et al. Lewy body-related alpha-synucleinopathy in aging. J Neuropathol Exp Neurol 2004;63:742-9.

  9. McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996;47:1113-24.

  10. Luis CA, Barker WW, Gajaraj K, et al. Sensitivity and specificity of three clinical criteria for dementia with Lewy bodies in an autopsy-verified sample. Int J Geriatr Psychiatry 1999;14:526-33.

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  Conflict of Interest:
  None declared.

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• Published on: 2 March 2005

  MIBG in clinical routine

  • Stefan Braune, Neurologist

  Dear Editor,

  Nagayama and colleagues report on the greatest number of patients with Parkinsonian syndromes undergoing MIBG scintigraphy sofar. They calculated a sensitivity of 87.7% and a specificity of 37.4% to correctly detect 122 patients with idiopathic Parkinson´s disease (PD) in relation to patients with MSA (n=14), dementia of Lewy body type (DLB) (5), PSP (7), senile dementia of Alzheimer type (SDAT) (...

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  Dear Editor,

  Nagayama and colleagues report on the greatest number of patients with Parkinsonian syndromes undergoing MIBG scintigraphy sofar. They calculated a sensitivity of 87.7% and a specificity of 37.4% to correctly detect 122 patients with idiopathic Parkinson´s disease (PD) in relation to patients with MSA (n=14), dementia of Lewy body type (DLB) (5), PSP (7), senile dementia of Alzheimer type (SDAT) (15), cerebrovascular disease (129) and other or unknown disorders (99).

  The rather disappointing specificity calculated is underscoring the true potential to correctly identify idiopathic Parkinson´s disease in clinical routine using MIBG scintigraphy. The heart/mediastinum ratio´s lower limit of normal of 1.84 is based on results from 10 normal subjects and surprisingly high. A meta-analysis of six MIBG studies in neurodegenerative disorders provided a lower limit of normal of 1,75 based on 69 normal subjects [1], others recently reported 1,69 in 19 normal subjects [2]. This would allow to correctly identify almost all patients with MSA in this study, as previously reported [3,4]. It is well established that disorders with development of Lewy bodies, like DLB, are associated with highly reduced cardiac MIBG uptake [5,6,7]. Interestingly none of these 3 studies comparing DLB and SDAT patients [5,6,7] could identify a single patient out of 34 patients with SDAT showing a reduced H/M ratio, while grossly reduced H/M ratios were measured in almost all patients in Nagayama´s study. Therefore inclusion of these two patient groups in the calculation of the specificity is contradictory to the current state of knowledge or raises doubts regarding the correctness of the diagnosis of SDAT. Summing up patients with DLB, SDAT, other disorders and unknown causes, the majority of 119 patients of the 269 patients with disorders other than PD provide well known pathological, surprisingly pathological or open pathological H/M ratios. This clearly limits the significance of the specificity calculated. The reduced cardiac uptake in CVD seems to be a clinically important factor for falsly reduced H/M ratios and needs further clarification in thoroughly performed studies.

  Yours sincerely

  Stefan Braune

  Corresponding author:
  PD Dr. Stefan Braune
  Neurozentrum Prien
  Bernauer Str. 12
  83209 Prien, Germany
  Tel. +49-8051-1811
  Fax +49-8051-64500
  braune@neurozentrum-prien.de

  References

  1. Braune S. The role of cardiac metaiodobenzylguanidine in the differential diagnosis of parkinsonian syndromes. Clin Autonom Res 2001; 11:351-355

  2. Spiegel J, Mollers MO, Jost WH et al. FP-CIT and MIBG scintigraphy in early Parkinson's disease Mov Disord. 2005 in press

  3. Braune S, Reinhardt M, Schnitzer R et al. Cardiac uptake of [123I] MIBG separates Parkinson´s disease from multiple system atrophy. Neurology 1999; 53:1020-1025

  4. Satoh A, Serita T, Seto M et al. Loss of 123I-MIBG uptake by the heart in Parkinson's disease: assessment of cardiac sympathetic denervation and diagnostic value. J Nucl Med. 1999; 40(3):371-375

  5. Watanabe H, Ieda T, Katayama T et al. Cardiac (123)I-meta- iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2001;70(6):781- 783

  6. Yoshita M, Taki J, Yamada M. A clinical role for [(123)I]MIBG myocardial scintigraphy in the distinction between dementia of the Alzheimer's-type and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2001;71(5):583-588.

  7. Oide T, Tokuda T, Momose M, et al. Usefulness of [123I]metaiodobenzylguanidine ([123I]MIBG) myocardial scintigraphy in differentiating between Alzheimer's disease and dementia with Lewy bodies. Intern Med 2003;42(8):686-690

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  Conflict of Interest:
  None declared.

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