Images below require Macromedia's Flash Player to view

Neuroradiology Case of the Week

Case 100

Xiang Liu, MD, PhD and PL Westesson, MD, PhD, DDS

Clinical Presentation: A 54-year-old man, status-post liver transplant one month ago (end stage liver disease secondary to hepatitis C), presented with left facial droop, slurred speech, and had several falls. He was on Tacrolimus for immunosuppression.

Radiological Findings: Axial CT images showed swelling in the central pons with low density, which caused the fourth ventricle compression (Fig. 1). There were also several patchy lesions with low density in the periventricular and frontal subcortical areas (Fig. 2).
     T1-weighted images demonstrate very slight increased signal intensity within the basal ganglia with no abnormal signal intensity in T2-weighted and FLAIR images.
     On T2-weighted and FLAIR images, there was diffuse high-signal within the pons, mesencephalon, the splenium of corpus callosum, and bilateral middle cerebellar peduncles. There was also multiple foci of increased signal intensity in the white matter diffusely and in the periventricular region, corona radiata, centrum semiovale and bilateral frontal, temporal, occipital and parietal subcortical area. These lesions were iso- or slightly hypointensity on T1-weighted images.
     Diffusion-weighted images demonstrated increased signal in the splenium of the corpus callosum and in the middle cerebellar peduncles, but with decreased signal in ADC map (Figs. 3-5).
     The lesions in the pons and frontal, temporal, occipital and parietal subcortical area were without evident abnormal signal on the diffusion weighted images, and with slightly high-signal on the ADC images (Figs. 6-8).
     After the administration of gadolinium there is no evidence of abnormal enhancement.

Diagnosis: Status post-liver transplant and toxic encephalopathy. Central pontine and extrapontine myelinolysis.

Clinical Discussion:  The basal ganglia high-signal on T1-weighted images may be seen as chronic lesions due to deposit of toxic metabolites and/or paramagnetic manganese [1-3]. Nagele et al. [2] indicated that the metabolite change of these lesions were with the decrease of myo-inositol/creatine and choline/creatine ratios and elevated ratio of glutamine and glutamate/creatine. The high-signal is potentially reversible and spectroscopy ratios also could change to normal after successful liver transplant.
     Central pontine myelinolysis (CPM), first described in 1959 by Adams et al. [4] in patients with a history of alcoholism and malnutrition, is characterized by symmetrical loss of myelin in the basis pontis, with relative preservation of axons and neuronal cell bodies.
     The extrapontine alterations were termed as extrapontine myelinolysis (EPM). With the application of magnetic resonance imaging (MRI) early recognition of CPM and EPM became feasible.
     Central Pontine Myelinolysis (CPM) is a neurologic complication after orthotopic liver transplantation (OLT) that was first described by Starzl et al. [5]. Some authors thought the cause of CPM is related with rapid corrections of hyponatremia or osmotic shifts after OLT [6,7], but more believe it is caused by tacrolimus-induced neurotoxicity related to the occurrences of CEPM after OLT [8-10].
     On regular MR imaging, CEPM lesions are hyperintense on T2-weighted images and hypointense on T1-weighted images. With widespread application of FLAIR, these lesions are more conspicuous with high-signal on FLAIR images. On DWI images, these lesions could be divided into two groups. The lesions in the first group are without evident high-signal on DWI, but with high-signal on ADC images, which means extravasation of fluid into the brain (vasogenic edema) [8-10]. The lesions in the second group have high-signal on DWI, and low-signal on ADC images, which means cytotoxic edema [10-12].
     According to the pharmacological study of tacrolimus [13], its neurotoxicity pathogenesis was speculated as follows: Firstly, tacrolimus itself may exert a direct neurotoxic effect, disrupt the blood barrier, or interfere with cerebrovascular autoregulation, which causes extracelluar edema. Many reports reveal this edema as strikingly reversible. It should be noted that the subcortical lesions are located in the brain anastomotic border zone, which is not consistent with regular ischemic infarctions [8].
     Secondly, the disrupt of BBB causes the cross of tacrolimus, then the high lipid content of myelin in the brain makes it an attractive binding site because FK506 has lipophilic properties. The axonal swelling, astrocytic swelling and compression of myelin contribute to the restricted diffusion which shows as high-signal on DWI images and low-signal on ADC images [11,12].

References:

1. Krieger D, Krieger S, Jansen O, Gass P, Theilmann L, Lichtnecker H. Manganese and chronic hepatic encephalopathy. Lancet 1999;346: 270-274.
2. Naegaele T, Grodd W, Viebahn R, et al. MR imaging and 1H spectroscopy of brain metabolites in hepatic encephalopathy: time-course of renormalization after liver transplantation. Radiology 2000; 216:683-691.
3. Genovese E, Maghnie M, Maggiore G, et al. MR imaging of CNS involvement in children affected by chronic liver disease. AJNR. 2000;21: 845-851.
4. Adams RD, Victor M, Mancall EL. Central pontine myelinolysis. Arch Neurol Psychiatry 1959;81:154–72.
5. Starzl TE, Schneck SA, Mazzoni G, et al. Acute neurological complications after liver transplantation with particular reference to intraoperative cerebral air embolus. Ann Surg 1978;187:236-240.
6. Abbasoglu O, Goldstein RM, Vodapally MS, Jennings LW, Levy MF, Husberg BS, Klintmalm GB. Liver transplantation in hyponatremic patients with emphasis on central pontine myelinolysis. Clin Transplant 1998;12:263-269.
7. Brown WD. Osmotic demyelination disorders: Central pontine and extrapontine myelinolysis. Curr Opin Neurol 2000;13:691-697.
8. Furukawa M, Terae S, Chu BC, et al. MRI in seven cases of tacrolimus (FK-506) encephalopathy: utility of FLAIR and diffusion-weighted imaging. Neuroradiology 2001;43(8):615-21.
9. Ahn KJ, Lee JW, Hahn ST, et al. Diffusion-weighted MRI and ADC mapping in FK506 neurotoxicity. Br J Radiol. 2003;76(912):916-9.
10. Shimono T, Miki Y, Toyoda H, et al. MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients. Eur Radiol. 2003 May;13(5):986-93.
11. Cramer SC, Stegbauer KC, Schneider A, et al. Decreased diffusion in central pontine myelinolysis. AJNR 2001; 22(8):1476-9.
12. Chu K, Kang DW, Ko SB, Kim M. Diffusion-weighted MR findings of central pontine and extrapontine myelinolysis. Acta Neurol Scand. 2001;104(6):385-8.
13. Misawa A, Takeuchi Y, Hibi S, et al. Fk506-induced intractable leukoencephalopathy following allogeneic bone marrow transplantation. Bone Marrow Transplantation 2000;25:331-334.