Neurology -- Correspondence for Walter et al., 60 (1) 74-77

Correspondence published:

Reply to Letter to the Editor: Uwe Walter (25 April 2003)

Brain parenchyma sonography discriminates Parkinson’s disease and atypical parkinsonian: V L Marshall, D G Grosset (25 April 2003)

Reply to Letter to the Editor 25 April 2003

Uwe Walter
Rostock University Germany
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Re: Reply to Letter to the Editor

uwe.walter{at}med.uni-rostock.de Uwe Walter

We appreciate the comments by Marshall and Grosset and respond as follows:
1) Their point holds true for any method used for discrimination between PD and atypical parkinsonian syndromes. Before a new diagnostic tool such as brain parenchyma sonography (BPS) is applied to clinically uncertain cases, its sensitivity and specificity need to be demonstrated in cases fulfilling strictest available clinical criteria. So far, we are unaware of any other diagnostic method, applied pre-mortem, being validated in clinically uncertain cases. Compared with other methods, BPS has the advantage of non -invasiveness and short investigation times. Together with high positive predictive values in syndrome discrimination, [1] we believe, that this advantage suggests BPS as a standard investigation. In clinical practice, still a synopsis of several clinical, imaging, and neurophysiological investigations will be necessary to improve diagnostic accuracy in uncertain cases.
2) All PD patients investigated fulfilled UK Parkinson's Disease Society Brain Bank criteria for definite PD.
3) Becker et al. investigated 30 PD patients with an ultrasound system of former generation and found normal substantia nigra (SN) echogenicity in 18 (60%) and SN hyperechogenicity in 12 (40% cases). [2] The same group found SN hyperechogenicity in 94 of 103 (91%) PD patients, using a sophisticated ultrasound system, which reflects the improvement of ultrasound technology. [3] In this study, extent of SN echogenicity was not related to PD duration, severity, or phenomenology. We detected SN hyperechogenicity in 96% and 100% of PD patients and also failed to find any correlation with disease duration or severity. [1, 4] The finding of SN hyperechogenicity in 9% of young healthy subjects corresponds to decreased caudate and putamen 18F-Dopa uptake on PET scanning. [5] In a study of 93 elderly healthy subjects without prediagnosed extrapyramidal disorder, those with SN hyperechogenicity had more frequent and severe motor deficits resembling PD than those with a normal echogenicity of the SN. [6] In a recent study, we investigated symptomatic and asymptomatic parkin mutation carriers (PMC) with BPS and detected SN hyperechogenicity in all symptomatic PMC and asymptomatic PMC with abnormal PET of the nigrostriatal system. Half of asymptomatic PMC showed normal PET and SN echogenicity. However, in the other half of asymptomatic PMC with normal PET, SN hyperechogenicity could be detected. [7] Data of this recent study suggest SN hyperechogenicity as an early finding indicating preclinical PD.
References:
1) Walter U, Niehaus L, Probst T, Benecke R, Meyer BU, Dressler D. Brain parenchyma sonography discriminates Parkinson's disease and atypical parkinsonian syndromes. Neurology 2003;60:74-77.
2) Becker G, Seufert J, Bogdahn U, Reichmann H, Reiners K. Degeneration of substantia nigra in chronic Parkinson's disease visualized by transcranial color-coded real-time sonography. Neurology 1995;45:182- 184.
3) Berg D, Siefker C, Becker G. Echogenicity of the substantia nigra in Parkinson's disease and its relation to clinical findings. J Neurol 2001;248:684-689.
4) Walter U, Wittstock M, Benecke R, Dressler D. Substantia nigra echogenicity is normal in non-extrapyramidal cerebral disorders but increased in Parkinson's disease. J Neural Transm 2002;109:191-196.
5) Berg D, Becker G, Zeiler B, et al. Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology 1999:53:1026-1031.
6) Berg D, Siefker C, Ruprecht-Dorfler P, Becker G. Relationship of substantia nigra echogenicity and motor function in elderly subjects. Neurology 2001;56:13-17.
7) Walter U, Klein C, Hilker R, Benecke R, Pramstaller P, Dressler D. Brain parenchyma sonography detects preclinical Parkinson' disease. Annals of Neurology in press.

Brain parenchyma sonography discriminates Parkinson’s disease and atypical parkinsonian 25 April 2003

V L Marshall
United Kingdom,
D G Grosset
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Re: Brain parenchyma sonography discriminates Parkinson’s disease and atypical parkinsonian

v.marshall{at}clinmed.gla.ac.uk V L Marshall, et al.

We read with interest the article by Walter et al. regarding sonographic findings in brain parenchyma in PD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). [1] However, we regard the conclusion that this might become a standard investigation to aid discrimination of PD from atypical parkinsonian syndromes (MSA, PSP) as premature.
We would like to comment as follows: 1) This study examined patients with established disease with a mean disease duration of 5.7 years for PD, 3.7 years for MSA and 4.8 years for PSP and clinically probable syndromes. Confirmation of syndrome type at this stage is not as helpful as detection would be at an earlier disease stage when diagnosis is clinically uncertain. Before this test can be deemed useful clinically it must show adequate sensitivity and specificity in patients with clinically uncertain parkinsonian syndromes where the differential diagnosis is between PD and MSA or PSP. In the absence of gold-standard post-mortem data long-term follow-up must take place to ensure congruence between emerging signs and sonographic data.
2) We are informed that the MSA and PSP group comprises of patients with clinically probable syndromes, including the information that eight of nine patients in the PSP group met NINDS criteria. It would be helpful to have similar information on PD cases; in particular the proportion fulfilling Step 1 and Step 3 3 Brain Bank Criteria.
3) Becker et al. reported that patients with PD and normal echogenicity in the substantia nigra had shorter disease duration than those with hyperechogenicity. [2] This raises questions about specificity and sensitivity of sonography in earlier disease when clinical uncertainty is higher and therefore when the test is potentially of greater use.
We fully accept that initial application of a new diagnostic test has to be performed in patients fulfilling available clinical criteria, and commend the authors on their undertakings so far.
References:
1. Walter U, Niehaus L, Probst T, Benecke R, Meyer BU, Dressler D. Brain parenchymal sonography discriminates Parkinson's disease and atypical parkinsonian syndromes. Neurology 2003;60:74-77.
2. Becker G, Seufert J, Bogdahn U, Reichmann H, Reiners K. Degeneration of substantia nigra in chronic Parkinson's disease visualised by transcranial color-coded real-time sonography. Neurology 1995;45:182- 184.