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|ADVERSE DRUG REACTION REPORT
|Year : 2014 | Volume
| Issue : 4 | Page : 394-396
Cerebellar superficial siderosis of chronic subarachnoid hemorrhage in a patient with Tacrolimus-associated posterior reversible encephalopathy
S Payabvash, AM McKinney, D Nascene, Z Cayci
Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA
|Date of Web Publication||5-Nov-2014|
Dr. S Payabvash
Department of Radiology, University of Minnesota, Minneapolis, Minnesota
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Payabvash S, McKinney A M, Nascene D, Cayci Z. Cerebellar superficial siderosis of chronic subarachnoid hemorrhage in a patient with Tacrolimus-associated posterior reversible encephalopathy. J Postgrad Med 2014;60:394-6
|How to cite this URL:|
Payabvash S, McKinney A M, Nascene D, Cayci Z. Cerebellar superficial siderosis of chronic subarachnoid hemorrhage in a patient with Tacrolimus-associated posterior reversible encephalopathy. J Postgrad Med [serial online] 2014 [cited 2022 Jan 19];60:394-6. Available from: https://www.jpgmonline.com/text.asp?2014/60/4/394/143968
In this paper, we present a patient of posterior reversible encephalopathy syndrome (PRES), following liver transplantation, that showed evidence of chronic subarachnoid hemorrhage (SAH) on 2-month follow-up susceptibility-weighted-images (SWI) scan with cerebellar superficial siderosis. The patient did not have evidence of intracranial hemorrhage (ICH) in her initial scans.
The patient was a 44-year-old Caucasian female who was admitted with a history of end-stage liver disease secondary to alcohol abuse, hepatitis C infection, and hemochromatosis. She presented with decompensation of liver function,and underwent deceased donor orthotopic liver transplantation. Her pre-transplantation head CT were unremarkable. Three weeks post transplantation, she became unresponsive with partial status epilepticus, marked aphasia, and partial cortical blindness. Noncontrast cerebral CT at 3 weeks showed scattered white matter hypodensities, predominately in the parietal and occipital lobes, which were suggestive of PRES [Figure 1]. The MRI showed bilateral cortical and subcortical FLAIR hyperintensities, predominantly in the parieto-occipital regions [Figure 2]. Her PRES was attributed to post transplant Tacrolimus treatment, which she has been taking for 5 days orally (2.5 mg twice daily for 3 days and then 4.5 mg twice daily for 2 days). Her serum Tacrolimus level ranged between 3.0 and 16.6 μg/L (normal 5 - 15 μg/L). Her serum Tacrolimus level post transplant ranged between 3.0 and 16.6 μg/L. Tacrolimus was discontinued and replaced by Rapamycin (3 mg daily) and then Cyclosporine (100 mg twice daily), both orally. Of note, her INR remained below 1.17 international units and her PTT remained below 33 seconds throughout the hospitalization. Her highest recorded blood pressure during hospitalization was 153/104 mm Hg. She was started on Levetiracetam (500 mg twice daily) for her symptoms, with marked improvement within a week. Her follow-up MRI, 6 days after the initial scan, demonstrated a decrease in size of T2 FLAIR hyperintense lesions, especially in the left hemisphere [Figure 3]. However, SWI and/or T2* images were not included in these two initial MRI studies. Approximately 9 weeks after the initial presentation of PRES symptoms, the patient reported near-complete resolution of neurological symptoms with minimal tremor and some speech difficulty. Her MRI at this time point showed cerebellar superficial siderosis, suggestive of hemosiderin deposition, as well as intraventricular susceptibility abnormalities with blooming artifact [Figure 4]. Notably, the absence of concomitant hyperintensity on FLAIR images was suggestive of chronic SAH.
|Figure 1: Axial noncontrast head CT (26 days post liver transplantation),when the patient had altered mental status and seizure-like movements, shows multiple areas of subcortical hypodensities mainly in the occipital and parieto-occipital junction. No evidence of intracranial hemorrhage|
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|Figure 2: On axial T2 FLAIR images (upper row), obtained the day after presentation of neurologic symptoms (27 days after transplantation); there is cortical and subcortical T2 FLAIR hyperintensities in bilateral parieto-occipital regions, as well as in bilateral basal ganglia and subinsular regions. On axial DWI/ADC (lower row), there is mild diffusion restriction in areas of the T2 FLAIR hyperintensity, especially in the left parieto-occipital region. There was no evidence of intracranial hemorrhage|
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|Figure 3: Axial T2 and FLAIR images (upper row), obtained 7 days after the onset of neurological symptoms, demonstrate subcortical T2/FLAIR hyperintensities predominantly in the parietal and occipital lobes, as well as bilateral basal ganglia.There has been interval decrease in T2 FLAIR hyperintensity since earlier scan [Figure 2], especially in the left hemisphere.Axial DWI/ADC (lower row) Images showed interval resolution of the restricted diffusion since earlier MRI study [Figure 2]|
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|Figure 4: Axial susceptibility-weighted-images (SWI, upper row), obtained 9 weeks after neurological symptom onset, demonstrate susceptibility changes in the subarachnoid space shown along the cerebellar folia (arrows); and blooming artifact in bilateral ventricles tracking into the temporal horns (arrow heads). The axial non-contrast T2 FLAIR images (lower row) show resolution of the hyperintense lesions since prior scan|
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PRES is a clinical and radiological condition characterized by headache, altered mental status, visual deficit, and seizures. Brain MRI/CT show potentially reversible predominantly vasogenic edema of the white matter with a predilection to the posterior circulation territory. A number of atypical imaging features of PRES have been described, including hemorrhage, cytotoxic edema (on DWI), and contrast enhancement. ,, The present case also showed typical T2 hyperintense lesions in the occipital and parietal subcortical white matter with cortical extension; with some lesions showing mild diffusion restriction, which were resolved within a week [Figure 3].
PRES-related ICH presents in three forms: Parenchymal microhemorrhage, intraparenchymal hematoma formation, and SAH.  While prior studies have demonstrated ICH in 15-32% of patients with PRES [Table 1], McKinney et al. have shown that the rate of cerebral parenchymal microhemorrhage can be as high as 58%, with an overall rate of 65% for any type of hemorrhage, if the cerebral parenchyma is evaluated with SWI. ,,,,, SAH in patients with PRES is usually restricted to the cerebral convexities and cortical, sparing the basal cisterns, which is uncommon in patients with aneurysmal rupture. 
|Table 1: Rate of intracranial hemorrhage and non-aneurysmal subarachnoid hemorrhage in patients with PRES|
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Superficial siderosis is caused by repeated hemorrhage into the subarachnoid space, with resultant hemosiderin deposition along the leptomeninge and subpial tissues, especially along the cerebellar sulci. It is commonly seen with CNS cancer, head trauma, vascular malformation, and amyloid angiopathy. Clinically, superficial siderosis is associated with sensorineural deafness, ataxia, pyramidal signs, and dementia; however, our patient reported no symptom on follow up. The time course between the hemorrhagic event and development of the superficial siderosis is still elusive.
The rate of Tacrolimus-associated PRES following allogeneic hematopoietic stem cell transplantation was reported at 1.6%.  The precise mechanism of Tacrolimus-associated PRES remains elusive. Experimental studies have shown direct cytotoxic effects of Tacrolimus on the brain capillary endothelial cells.  Neuropathologic evaluation of a case of Tacrolimus-associated PRES in a liver transplantation patient has demonstrated white matter vasogenic edema in the absence of infarcts or demyelination.  It has also been hypothesized that increased urinary magnesium wasting and hypomagnesemia, following Tacrolimus therapy, predispose patients to hypertension, renal impairment, cerebral vasoconstriction, and encephalopathy. 
To our knowledge, this is a unique report of chronic SAH and cerebellar superficial siderosis found in a patient with PRES based on SWI findings. More widespread application of SWI sequences is expected to show a higher rate of microhemorrhage among PRES patients. Of note, PRES patients with transplantation (specially bone marrow transplant) and those who are therapeutically anticoagulated are more likely to have hemorrhage,  and may benefit the most from evaluation with SWI.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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