Corticosteroids in posterior reversible encephalopathy syndrome: Friend or foe? A systematic review

Table 3 Cases of posterior reversible encephalopathy syndrome that included corticosteroids in the treatment plan

Case No.	Ref.	Age (year)	Sex	Clinical sequela	BP (mmHg)	MRI findings	Vessel imaging	CSF studies	Cause	LOS (days)	Management	Outcomes
1	Aridon et al[58], 2011	53	M	Elevated blood pressure, gait disturbance, dizziness, urinary incontinence, and lethargy	260/180	MRI showed signals in both sides of the white matter of the cerebral and cerebellar hemispheres with involvement of the cerebellar peduncles and midbrain. A triventricular hypotheses hydrocephalus, a result of brainstem oedema, was observed	N/A	A lumbar puncture was performed. It revealed a normal cell count (0.8/mm3) along with limpid and uncolored CSF. Also slightly higher total protein concentration (77mmg/mL, normal is less than 40 mg/mL)	TTP	N/A	High-dose methylprednisolone and plasma exchange therapy	Follow up: 6 months later the neurological examination was normal and 24 months later he did not relapse and is still healthy. Outcome: Brain magnetic resonance imaging revealed almost complete resolution of brainstem oedema and changes in abnormal T2 signals
2	Christofidis et al[59], 2019	20	F	Generalized arthralgia, high grade fever (up to 39 degrees C), and severe headaches	140/70	DWI was normal with no sign of restricted diffusion. The MRI revealed leptomeningeal enhancement and bilateral subcortical lesions in the parietal-occipital regions on T2/FLAIR images, indicating vasogenic edema was present there	MRA demonstrating constriction and vasospasm of the cerebral arteries	Both PCR tests of CSF and blood were found to be positive for Neisseria meningitis (serogroup B). Both culture and Gram stain were negative for CSF. The white blood cell count was 15 K/uL, indicative of neutrophilic pleocytosis. The glucose level was low at 1 mg/dL and elevated protein concentrations at 352.01 mg/dL	Infection, sepsis	23	The patient was given mannitol, dexamethasone, the antiepileptic drug levetiracetam, and Ceftriaxone. Endotracheal intubation was also performed	Follow up: Follow-up MRI of both T2 and FLAIR images showed on the 23rd day complete resolution of the hyperintense and diffuse lesions in the parietal-occipital brain regions. The MRA follow-up was normal. Outcome: Mental status was completely restored 3-4 days after initiation of treatment, rapid recovery
3	Hao et al[60], 2021	28	F	Anasarca and tachycardia	107/79	MRI showed an abnormal high signal intensity in T2-weighted imaging, FLAIR, and ADC maps. In addition, low signal intensities on T1-weighted imaging and DWI were revealed. These were found in the parietal, bilateral frontal, occipital, temporal, basal ganglia, and cerebellar hemispheres	N/A	Increased protein levels	Autoimmune inflammation or ischemic changes that resulted from SLE (such as vasculitis, embolism, thrombus, and vasospasm) lead to endothelial dysfunction and, subsequently, to PRES. The author acknowledges that PRES could have been caused by corticosteroids, but ultimately was used to help treat PRES	Approximately 12	The patient was administered corticosteroids with methylprednisolone at 160 mg/day for inflation. She was sedated and also administered antiepileptic, acid suppression medications, and antipyretic. Once symptoms returned, methylprednisolone was administered 1000 mg/day for 3 days, 20 mg of dexamethasone, 10 mg of intrathecal injection and 60 mg of prednisone tablets in the morning. Immunosuppressant agents were administered hydroxychloroquine sulfate at 0.2 g twice a day, r-globulin at 20 g once a day for 5 days, and cyclophosphamide at 0.4 g per week as needed	Follow up: Condition stable. Outcome: Lesions were mostly resolved
4	Hosseini[61], 2022	40	F	Severe and refractory headache with multiple convulsive events	160/90	T2WI: Vasogenic edema in occipito-parieto-frontal lobes white matter compatible with PRES. Hyperintensities in occipito-parieto-frontal white matter with predominance in occipital lobes, without any restriction in diffusion weighted sequences (DWI), compatible with brain edema. Cervical cord MRI was normal too	MRV was normal	Although the IgG index in CSF was 0.7, CSF analysis was normal and the oligoclonal bands were negative	N/A	N/A	Adjuvant levetiracetam.IVMP, 1000 mg/day	Follow up: N/A. Outcome: After three days of IVMP, her headache completely subsided and a control brain MRI showed resolution of most hyperintense regions
5	Islam et al[62], 2021	29	F	Seizures, drowsiness, fever, occasional headache, muscle weakness	N/A	T2WI: Symmetrical hyperintensities over posterior brain regions in T2 and fluid attenuated inversion recovery images with no restricted diffusion in diffusion weighted image suggestive of PRES	N/A	Normal cell count 5/mm3 (n = 0–10), elevated protein 69 g/dL (n = 20–40). She also had a normal sugar and antideaminase level	N/A	N/A	Methylprednisolone and monthly cyclophosphamide (patient responded well to these). Levetiracetam, O2, normal saline. Low dose of oral prednisolone Hydroxychloroquine	Follow up: N/A. Outcome: Improvement in all aspects
6	Jadib et al[63], 2021	11	F	Tonic-clonic seizures, nausea, abdominal pain, headaches, and a more recent onset of blurred vision, HTN	161/109	Low signal on T1-weighted images and high signal on T2-weighted images, high apparent diffusion coefficient with no hemorrhage	N/A	N/A	Left renal artery stenosis due to TA	N/A	Intrarectal diazepam Nicardipine Amlodipine and propranolol azathioprine and corticosteroid given	Follow up: 11 months later MRI revealed total resolution. Outcome: Showed neurological improvement
7	Mai et al[64], 2018	55	F	Confused, speech slurred, convulsions, upgoing plantar reflex, vertical gaze palsy	140/90	T2WI: Involving periventricular and deep cerebral white matter. Repeat MRI showed resolution	CSF: Opening pressure of 12 cm H2O, cell count of 7 cells/ µL, a red cell count of 4 cells/µL, protein level of 4.4 g/ dL, a glucose level of 4.76 mmol/L (10.4 mmol/L in blood), and a lactate level of 3.25 mmol/L. Dengue virus IgM was detected in CSF	N/A	Dengue infection	59 days	Intravenous methylprednisolone, oral prednisolone, and Phenobarbital given	Follow up: N/A. Outcome: Patient was discharged for rehab and a repeat MRI showed almost complete resolution
8	Min et al[65], 2006	22	F	Headaches, blurred vision, vertigo, nausea, vomiting, and altered mental function, binocular blindness, seizure, and lethargic	200/110	T2WI: Cerebellum, brainstem, basal ganglia, and central white matter. These abnormalities resolved	MRA was normal	20 RBC/L, 1 WBC/L, protein 106 mg/dL (normal range 10 to 40 mg/dL), and glucose 46 mg/dL (normal range 40 to 70 mg/dL)	Hypertension is possible in this context	14 days at least	Cyclophosphamide, methylprednisolone, dialysis, diazepam, fosphenytoin, Phenytoin, mycophenolate mofetil, and dialysis were performed. Methylprednisolone 1 g IV for 2 days. Plasmapheresis	Follow up: N/A. Outcome. Stopped hemodialysis after renal function improved
9	Ortega-Carnicer et al[66], 2005	24	M	Generalized seizures, deep coma, flaccid tetraplegia, and fixed dilated pupils	225/120	N/A	N/A	N/A	PRES was induced by immunoglobulin administration due to the temporal relationship between immunoglobulin administration and the onset of neurological symptoms of PRES	Approximately 25	Treatment with IVMP (1000 mg/24 hours) resulted in neurological improvement	Follow up: N/A. Outcome: In good neurological condition
10	Sato et al[67], 2011	42	F	Throbbing headache, drowsiness	N/A	MRI T2-weighted imaging revealed hyperintense lesions in the occipital and temporal-parietal lobes. Diffusion weighted images revealed bilateral and symmetric hyperintense lesions in the occipital lobe	The right posterior cerebral artery experienced vasoconstriction according to MRA	N/A	Treatment with methylprednisolone helped reverse cerebral edema	68	Treatment included methylprednisolone and glycerin	Follow up: MRA returned to normal 6 months after discharge. Complete recovery of the lesions on day 64. Outcome: N/A
11	Symeonidis et al[68], 2021	75	M	Mental status decline, lethargic, disoriented, episodes of hypertensive crisis	180/100	MRI FLAIR and T2-weighted images revealed signal hyperintensity in the bilateral areas of thalamus, fibers of reticular formation, hypothalamus, mild edema of left parahippocampal gyrus, and anterior section of cerebral vermis	N/A	The lumbar puncture revealed negative cytology for metastatic cells. Gram-positive and negative bacteria, herpes zoster, EBV, HSV, BK, CMV, JC, influenza, adenovirus, fungal causes, tuberculosis, listeria, borrelia, and other cultures were negative	Oxaliplatin was the main cytotoxic agent that led to PRES	N/A	Treatment was with dexamethasone and antiepileptics	Follow up: Neurological resolution of PRES after 3-4 weeks. Outcome: Clinical improvement
12	Tetsuka and Nonaka[69], 2017	38	F	Drowsy but conscious, delirium and fluctuating mental stability.	150/90	T2WI/ADC: Revealed hypersignal intense lesions in the cortical and subcortical white matter in the basal ganglia, callosal splenium, and occipital lobes	N/A	N/A	Corticosteroids helped reduce vasogenic edema	21	Intravenous corticosteroids and nifedipine	Follow up: MRI two weeks after her initial MRI revealed complete resolution. Outcome: Laboratory results and MRI became normal
13	Xia and Lv[70], 2022	58	M	Drowsiness, left hemiparesis, lethargy, impaired attention and memory	169/94	T2WI: Subcortical hyperintensities in the left and right hemispheres, mainly in the temporal and occipital lobe. ADC revealed increased diffusivity of legions that represent vasogenic edema. SWI: Cortical and subcortical CMBs in the bilateral temporal lobes	N/A	CSF: 13 cells/mm3 (mononuclear cells-10 cells/mm3, polynuclear cells-3 cells/mm3). Elevated total protein concentration revealed 207 mg/dL and an opening pressure of 400 mmH2O. No oligoclonal IgB bands were detected in the analysis. However, both immunoglobulin IgG and albumin increased significantly at 464 mg/L and 1.57 g/L, respectively. The IgG index was slightly higher at .89 in comparison to normal, which is less than or equal to 0.70	PRES was caused by shock wave lithotripsy and HTN	24	High-dose oral methylprednisolone (500 mg/day) for 5 days, dehydration therapy, prednisolone 60mg/day with a decrease dose of 5 mg every 10 days	Follow up: MRI 3 months after discharge revealed most resolution of white matter hyperintensities without CMB in SWI
14	Xu et al[71], 2021	14	F	Tonic clonic seizures, auditory hallucinations, disorder of thought	150/100	T2-weighted and FLAIR revealed hyperintense lesions in the parietal, occipital, temporal, and frontal lobe, subcortex, and cerebral cortex. Diffusion-weighted magnetic resonance imaging and apparent diffusion coefficient revealed isointense and hyperintense lesions	MRA was normal	N/A	Methylprednisolone was used to treat MPA, which in return cured the PRES	N/A	200 mg of methylprednisolone and 7 courses of plasma exchang	Follow up: No PRES relapse. Outcome: 17 days later, reduced gyrus swelling was observed

BP: Blood pressure; MRI: Magnetic resonance imaging; CSF: Cerebrospinal fluid; LOS: Length of stay; DWI: Diffusion-weighted imaging; MRA: Magnetic resonance angiography; SLE: Systemic lupus erythematosus; MRV: magnetic resonance venography; IVMP: Intravenous methylprednisolone pulse; TTP: thrombotic thrombocytopenic purpura; PRES: Posterior reversible encephalopathy syndrome; T2WI: T2-weighted imaging; DWI: Diffusion-weighted imaging; HTN: Hypertension ; TA: Transient amnesia; RBC: Red blood cell; WBC: White blood cell; EBV: Epstein Barr virus; HSV: Herpes simplex virus; CMV: Cytomegalovirus; JC: JC virus; ADC: Apparent diffusion coefficient; CMB: Cerebral microbleed; SWI: susceptibility weighted imaging; N/A: Not applicable.