Table 1.

Patient characteristics of patients with CNI‐induced neurotoxicity

Case	Case 1	Case 2	Giusanni	Niemi	Vernon	Mc Guire	Nagarajan
Year publication, gender	2019, f	2019, f	2016, m	2015, m	2014, f	2008, m	2005, m
Age onset, age at diagnosis	5 mo, 5 mo	12 days, un	un, <1 y	both un	3 mo, 9 mo	<3 mo, 3 mo	1 week, 1 week
Genotype	Mut0 c.1311_1312insA, p.Val438Serfs*3 non‐vitamin B12 responsive	Mut0 c.2078delG, p.G693Dfs*12 non‐vitamin B12 responsive	un	un	Mut0 c.2053dupCTC p.685insL non‐vitamin B12 responsive	Mut0	Mut0
Neurologic complications pre‐Tx	None	None	un	un	Mild choreoathesosis due to bilateral globus pallidus infarction	Aphasic and difficulty ambulating due to weakness and tremors	Deterioration with dystonia, muscular weakness and wheelchair bound
Other complications pre‐Tx	Impaired vision due to optic nerve infarction, age 12 y ESRDa, age 18y, she required hemodialysis	Near blind from sudden onset optical atrophy, age 17 y Chronic renal insufficiency age 10y, stage IV age 18y	un	un	Acute bilateral opticus neuropathy, Chronic kidney diseaseb	Renal insufficiency, frequent metabolic decompensations	Pancreatitis
Development pre‐Tx	Normal: WAIS‐IV performed at age 27y: normal with mild expressive language problems	Normal	un	un	Normal	un	Cognitive development delay, decreased motor skills
Age Tx	28 y	19 y	6 y	un	28 y	5 y	21 y
Duration follow‐up	14mo	8 mo	un	un	un	10 mo	1 y 6 mo
Tx	Combined LKT	Combined LKT (lost renal Tx)	Combined LKT	Liver	Combined LKT	Combined LKT	Combined LKT
Medication after Tx	Tacrolimus, MMF, prednisone	Tacrolimus, MMF, prednisone	Cyclosporine, prednisone	Tacrolimus, prednisone, azathioprine	MMF, prednisone, basiliximab, POD 6 tacrolimus	Tacrolimus and steroids	Tacrolimus, sirolimus, prednisone
Start neurological symptoms post‐Tx	3 mo	22 days	10 days	12 days	28 days and 48 days	Weeks	un
Neurological symptoms	Bradyphrenia, severe ataxia, behavioural changes	Seizures	Seizures	Seizures	Seizures	Altered mental status, aphasia, hallucinations, seizures, tremor	Altered mental status, tremors
Tacrolimus level during neurological symptoms (ng/mL)	10.7	3.1‐5.5c	un	High	6.7	<5	5‐7
Mma levels during neurological symptoms (μmol/l)	272 in plasma, 728 in the cerebrospinal fluid	268 in plasma	un	<343 in plasma	un	<500 in plasma	<500 in plasma
Final consensus diagnosis	CNI‐induced PRES	Definite CNI‐induced neurotoxicity	CNI‐induced PRES	Definite CNI‐induced neurotoxicity	CNI‐induced PRES	Definite CNI‐induced neurotoxicity	Definite CNI‐induced neurotoxicity

Abbreviations: CNI, calcineurin inhibitor; combined LKT, combined liver and kidney transplantation; ESRD, end‐stage renal disease; f, female; m, male; mo, months; Tx, transplantation; un, unavailable; y, year.

^aDespite fluid up to 7 L/d via PEG.

^bSecondary hyperparathyroidism, hypothyroidism.

^cDeliberately lower in setting of combination therapy with MMF due to renal failure.