Neurology -- Correspondence for Meissner et al., 63 (3) 450-456

Correspondence published:

Reply to Iwasaki et al: Bettina Meissner, Inga Zerr, Dept. of Neurology, Georg-August University Göttingen, Robert -Koch Str. 40, 37075 Göttingen, Germany (2 December 2004)

Sporadic Creutzfeldt-Jakob disease: Magnetic resonance imaging and clinical findings: Yasuo Iwasaki, Osamu Igarashi, Yasumitsu Ichikawa and Ken Ikeda (2 December 2004)

Reply to Iwasaki et al 2 December 2004

Bettina Meissner,
Dept. of Neurology Georg-August University Göttingen, Germany
Robert-Koch Str. 40,
Inga Zerr, Dept. of Neurology, Georg-August University Göttingen, Robert -Koch Str. 40, 37075 Göttingen, Germany
Send Correspondence to journal:
Re: Reply to Iwasaki et al

betti.meissner{at}t-online.de Bettina Meissner, et al.

We read with great interest Iwasaki et al's correspondence regarding two CJD patients displaying low signal of the basal ganglia on T2-weighted MRI. In our series, no such abnormalities have been reported so far. The aim of our study, however, was the detection of high signal changes of the basal ganglia. It is possible that some cases of low signal changes might have been overseen. A study including all MRI abnormalities is currently underway.
As Dr. Iwasaki mentioned, iron deposition may lead to low signal especially with increasing age. [1] Unfortunately, we have no information on the age of the patients nor if any iron deposits could be found in the neuropathological examination given. In prion diseases signal increase on DWI has been supposed to be due to spongiform changes leading to reduced water diffusion as the vacuoles measure only 5 to 20 ƒÝm. [2] Signal increase on T2- and FLAIR-weighted images have been described to be dependent on gliotic changes - an observation best underlined by the pulvinar sign of the new variant of CJD (nvCJD), showing high signal of the pulvinar based on intense astrocytosis in this area.
Interestingly, in a hamster model, high signal on T2-weighted MRI correlated with marked gliosis and only little vacuolation, whereas, low signal was found in brain areas showing moderate to severe vacuolation and only little gliotic changes. Both kinds of lesions in an outweighed measure tended to show a normal signal on T2. [3] The authors, furthermore, reported high signal at initial stage (matching predominant gliotic changes) followed by a signal hypointensity during the course (matching increasing vacuolation). These findings might explain the observation of low signal in the two reported CJD patients.
In contrast to this hypothesis, there have been cases reported showing increasing signal on T2 during the disease course, whereas DWI signal (depending on vacuolation) was high already in the beginning. [4,5] It is important to consider that the MRI signal caused by the underlying neuropathological lesion pattern actually depends on a certain disease phenotype determined by the methionin-valin polymorphism of the prion protein gene and the type of prion protein (PrPSc type 1 or 2, Sc = Scrapie) and, possibly, also on the disease stage.
Further studies correlating MRI findings, neuropathological lesion patterns and phenotype will have to be performed.
References
1. Finkenstaedt M, Szudra A, Zerr I, Poser S, Hise JH, Stoebner JM, Weber T. MR imaging of Creutzfeldt-Jakob disease. Radiology 1996;199:793- 798.
2. Mittal S, Farmer P, Kalina P, Kingsley PB, Halperin J. Correlation of diffusion-weighted Magnetic Resonance Imaging with neuropathology in Creutzfeldt-Jakob disease. Arch Neurol 2002;59:128-134.
3. Chung Y, Williams A, Ritchie D, Williams SCR, Changani K, Hope J, Bell JD. Conflicting MRI signals from gliosis and neuronal vacuolation in prion diseases. NeuroReport 1999;10:3471-3477.
4. Demaerel P, Heiner L, Robberecht W, Sciot R, Wilms G. Diffusion- weighted MRI in sporadic Creutzfeldt-Jakob disease. Neurology 1999 ;52:205 -208.
5. Bergui M, Bradac GB, Rossi G, Orsi L. Extensive cortical damage in a case of Creutzfeldt-Jacob disease : clinicoradiological correlations. Neuroradiology 2003;45:304-307.

Sporadic Creutzfeldt-Jakob disease: Magnetic resonance imaging and clinical findings 2 December 2004

Yasuo Iwasaki,
Toho University Omori Hospital
6-11-1 Omorinishi Ota-ku Tokyo 143-8541 JAPAN,
Osamu Igarashi, Yasumitsu Ichikawa and Ken Ikeda
Send Correspondence to journal:
Re: Sporadic Creutzfeldt-Jakob disease: Magnetic resonance imaging and clinical findings

yaso{at}med.toho-u.ac.jp Yasuo Iwasaki, et al.

We read with interest the article by Meissner et al. [1] They reported 97 out of 157 patients with CJD had hyperintense signal in the basal ganglia on T2-weighted images. They also addressed the possible link with spongiform or gliotic changes in the brain tissues.
We had two cases with autopsy-proven CJD whose MRI exhibited low signal intensity in the putamen. Autopsies revealed typical findings in CJD including spongiform, neuronal loss, and gliosis. Clinical findings were characterized by dementia and myoclonus. Pyramidal signs were not seen in either case. Both of our cases also showed typical periodic sharp wave complexes on EEG. Both patients died nearly a year after onset. Molecular studies were not performed.
We would like to know if there was low signal intensity in basal ganglia in the T2-weighted images in their series. Basal ganglia hyperintensity in CJD has been reported. [2,3] They hypothesized that spongiform or gliotic changes could contribute to display hyperintense signal in the basal ganglia in T2 -weighted image. Our cases had gliosis and spongiform changes similar to the cases studied by Meissner et al but our MRIs showed low signal changes.
Taken together, high or low signal intensity could occur despite the same pathological conditions. Iron-deposition, hemosiderin, lipid deposits may produce hypointense signal but accumulation of these substances are not considerable in the brains of CJD patients. Further pathological and biochemical analyses are needed to clarify the MRI signal in CJD.
References
1. Meissner B, Köhler K, Körtner K. et al. Sporadic Creutzfeldt-Jakob disease: magnetic resonane imaging and clinical findings. Neurology 2004;63:450- 456.
2. Finkenstaedt M, Szudra A, Zerr I, et al. MR imaging of Creutzfeldt- Jakob disease. Radiology 1996;199:793-798.
3. Schröter A, Zerr I, Henkel K, Tschampa HJ, Finkenstaedt M, Poser S. Magnetic resonance imaging (MRI) in the clinical diagnosis of Creutzfeldt- Jakob disease. Arch Neurol 2000;57:1751-1757.