Neurology -- Correspondence for Bianco et al., 62 (6) 981-983

Correspondence published:

Reply to Turner: Federico Bianco, Francesco Fattapposta, Nicoletta Locuratolo, Alberto Pierallini, Franco Ruberto, Massimo Rossi and Luigi Bozzao. (26 July 2004)

Reversible diffusion MRI abnormalities and transient mutism after liver transplantation: Martin R Turner (26 July 2004)

Reply to Turner 26 July 2004

Federico Bianco,
University of Rome
Viale Università n.30, 00185 Rome, Italy,
Francesco Fattapposta, Nicoletta Locuratolo, Alberto Pierallini, Franco Ruberto, Massimo Rossi and Luigi Bozzao.
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Re: Reply to Turner

federico.bianco{at}uniroma1.it Federico Bianco, et al.

We thank Dr. Turner for his interest in our article. [1] He noticed, as did we, that the MRI abnormalities we described resemble those seen in ALS and suggests that these changes may occur as a result of a cerebral microenvironment under profound metabolic/oxidative stress.
The MRI abnormalities we described include those in the corticospinal tracts (CST) and in the frontal cortex and we made an effort to distinguish between them. The CST changes are similar to those in patients with liver failure which resolve with hepatic transplantation. [2] We believe that the cortical changes may be linked to cyclosporine toxicity. Since the mechanism of cyclosporine neurotoxicity is still unclear, the hypothesis that an oxidative stress (including mitochondrial dysfunction) might be involved in the setting of cyclosporine-induced MRI abnormalities is possible.
Dr. Turner also suggests that the CST and frontal lobe neuronal pathways are among the most vulnerable to metabolic/oxidative stresses whatever the underlying cause. Although the MRI abnormalities we observed are restricted to the frontal motor cortex, our patient may be considered a variant of Posterior Reversible Encephalopathy Syndrome (PRES), a symptom complex characterized in imaging studies by areas of signal abnormality in the posterior regions of the cerebral hemispheres. [6,7] As others have observed [8,9], the current term is in itself misleading because it does not account for the growing experience that is extending the concept of PRES. An adverse (not reversible) outcome has been reported in 27% of cases and an involvement of the frontal lobes has been detected in up to 82%. [10]
Since brain edema may determine these pathological changes, as demonstrated by Diffusion- MRI [1,7,10], it can be assumed that under some critical situations, such as immunosuppressant therapy in transplant patients and other conditions, an acute onset of focal edema may occur in the brain (often in the frontal lobes). A more generalized phenomenon, (i.e. focal or multi-focal) acute cerebral edema, may clarify the heterogeneous group of disorders in which similar MRI abnormalities can be observed. [10] Whether a similar mechanism is also involved in ALS needs to be further investigated and Diffusion-MRI will be useful.
References
6. Hinchey J, Chaves C, Appignani B et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494-500.
7. Casey SO, Sampaio RC, Michel E, Truwit CL. Posterior reversible encephalopathy syndrome: utility of FLAIR imaging in the detection of cortical and subcortical lesions. AJNR Am J Neuroradiol 2000;21:1199- 1206.
8. Schwartz R. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:1743 Letter.
9. Lewis MB, Howdle, PD. Neurologic complications of liver transplantation in adults. Neurology 2003;61:1174-78.
10. Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: prognostic utility of quantitative Diffusion- Weighted MR images. AJNR Am J Neuroradiol 2002;23:1038-1048.

Reversible diffusion MRI abnormalities and transient mutism after liver transplantation 26 July 2004

Martin R Turner,
Institute of Psychiatry
PO Box 41 (ANC), 16 De Crespigny Park, LONDON, SE5 8AF, UK
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Re: Reversible diffusion MRI abnormalities and transient mutism after liver transplantation

m.turner{at}iop.kcl.ac.uk Martin R Turner

Bianco et al report MRI abnormalities after hepatic transplantation. [1] Rovira et al described similar corticospinal tract (CST) hyperintesities in cirrhosis that resolved with hepatic transplantation [2], and both studies may clarify selective cortical vulnerability in disease.
In both cases, the changes were strikingly similar to CST abnormalities noted in cases of amyotrophic lateral sclerosis (ALS). [3] Clinically, CST involvement in ALS varies and such MRI findings are considered poor sensitivity and specificity indicators. However, Bianco et al's finding of frontal lobe abnormalities in the setting of hepatic disease is a further area of overlap with the cortical lesion in ALS, where a clear spectrum of frontal lobe involvement is now acknowledged, even within the majority of cases (who do not develop frank dementia) [4].
The cerebral MRI changes in the setting of hepatic failure are ascribed to edema. This might occur as a result of a cerebral microenvironment under profound metabolic/oxidative stress. There is growing evidence, fueled by the finding of mutations of the superoxide dismutase (SOD1) gene in a small number of ALS cases, to suggest that oxidative stress or metabolic derangements (including mitochondrial dysfunction) might be involved in the pathogenesis of ALS. [5]
The current observation that the same cerebral regions are involved in both severe (peri-transplantation) hepatic disease and ALS, might confirm this pathogenic concept. The corollary is that the CST and frontal lobe neuronal pathways are among the most vulnerable to metabolic/oxidative stresses whatever the underlying cause, and this may account for the apparent selective cortical neuronal vulnerability in cases of ALS.
References
1. Bianco F, Fattapposta F, Locuratolo N, et al. Reversible diffusion MRI abnormalities and transient mutism after liver transplantation. Neurology 2004;62:981-983.
2. Rovira A, Cordoba J, Sanpedro F, Grive E, Rovira-Gols A, Alonso J. Normalization of T2 signal abnormalities in hemispheric white matter with liver transplant. Neurology 2002;59:335-341.
3. Lee YC, Markus R, Hughes A. MRI in ALS: corticospinal tract hyperintensity. Neurology 2003;61:1600.
4. Lomen-Hoerth C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002;59:1077- 1079.
5. Agar J, Durham H. Relevance of oxidative injury in the pathogenesis of motor neuron diseases. Amyotroph Lateral Scler Other Motor Neuron Disord 2003;4:232-242.