Question 14.1
A 28-year-old female with ulcerative colitis on azathioprine and prednisolone was commenced on intravenous infliximab for the worsening of symptoms. Two weeks after the second cycle, she presented with headache, confusion and blurred vision followed by a generalised tonic-clonic seizure.
Cerebrospinal fluid analysis is unremarkable.
Slices from T2 weighted MRI scan of the brain are depicted below (Figure 1):
a) What is the most likely diagnosis?
b) List four risk factors for this condition.
College Answer
a)
- Posterior Reversible Leukoencephalopathy Syndrome
b)
- Hypertension
- Eclampsia / Pre-eclampsia
- Immunosuppressive therapy
- Auto-immune diseases
- Porphyria
- Acute or chronic renal diseases
- TTP / HUS
- Infection / sepsis / septic shock
Discussion
a)
This is PRES, the posterior reversible leukoencephalopathy syndrome. The images above were ripped off from the 2012 article by Swarnalatha et al. It has been associated with infliximab therapy, and is known in this context from a growing number of case reports (eg. Zamvar et al, 2009). It is also associated with sirolimus, thalidomide, gemcitabine, paclitaxel, carboplatin, sorafenib and the list goes on. According to Radiopedia, it can be recognised by the following MRI image features:
- Posterior distribution (but this is not essential)
- T1: hypointense in affected regions
- T1 C+ (Gd): patchy variable enhancement. It can be seen in ~35% of patients, whether leptomeningeal or cortical pattern.
- T2: hyperintense in affected regions
- DWI: usually normal
- ADC: signal increased in affected regions due to increased diffusion
- GRE: may show hypointense signal in cases of haemorrhage
- SWI: may show microhemorrhages in up to 50%
b)
Risk factors for PRES could include:
- Autoimmune disease
- Immunosuppressive therapy
- Eclampsia and pre-eclampsia
- Hypertension
PRES is almost exclusive to significant systemic conditions. . Classical associations include the following list (borrowed from Bartynski's Table 1):
- Solid organ transplant
- Bone marrow transplant
- Graft vs. host disease following allogenic BMT
- Immunosuppressant therapy
- Pregnancy (particularly, pre-eclampsia)
- Cancer chemotherapy
- Autoimmune disease, particularly scleroderma, SLE and Wegener's granulomatosis
- Sepsis and septic shock
The UpToDate article gives an even larger list of "associated conditions", which adds the following:
- TTP / HUS
- Cryoglobulinaemia
- Chronic kidney diseases
- Porphyria
- Blood transfusion
- Contrast media exposure
References
G Swarnalatha, R Ram, B. H. S. Pai, KV Dakshinamurty "Posterior reversible encephalopathy syndrome in minimal change disease" Indian Journal of Nephrology, Vol. 22, No. 2, March-April, 2012, pp. 153-154
Zamvar, Veena, et al. "Posterior reversible encephalopathy syndrome following infliximab infusion." Journal of pediatric gastroenterology and nutrition 48.1 (2009): 102-105.
Fugate, Jennifer E., et al. "Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings." Mayo Clinic Proceedings. Vol. 85. No. 5. Elsevier, 2010.
Staykov, Dimitre, and Stefan Schwab. "Posterior reversible encephalopathy syndrome." Journal of Intensive Care Medicine 27.1 (2012): 11-24.
Bartynski, W. S. "Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features." American Journal of Neuroradiology 29.6 (2008): 1036-1042.
Bartynski, W. S. "Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema." American Journal of Neuroradiology 29.6 (2008): 1043-1049.
Grioni, Daniele, et al. "The diagnosis of posterior reversible encephalopathy syndrome." The Lancet Neurology 14.11 (2015): 1073-1074.
Fugate, Jennifer E., and Alejandro A. Rabinstein. "Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions." The Lancet Neurology 14.9 (2015): 914-925.
MacKenzie, ERIC T., et al. "Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier." Circulation research 39.1 (1976): 33-41.