TABLE 2.

Published Cases of Progressive Multifocal Leukoencephalopathy in Patients Treated with Fumarates

Study	Disease	Treatment and Duration	Oncological History	Prior Immune Treatment	Lymphopenia	CD4/8 Counts	JCV PCR	Neurological Status Iris	MRI Manifestation
Ermis 201326	Psoriasis	Fumaderm, 3 yr	None	Methotrexate 3 yr before	Grade 3	CD3+, CD4+ T- cell deficiency, CD4/CD8 ratio > 2	90 copies/ml CSF	Progressive sensory aphasia; IRIS	Subcortical/ juxtacortical white matter
Van Oosten 201327	Psoriasis	Psorinovo, 5 yr	None	None	Grade 3	CD3+, CD4+, CD8+ T-cell defi- ciency, CD4/CD8 ratio = 2	Positive	Progressive right- sided hemiparesis, IRIS	Small, deep white matter lesions and 1 large progressive lesion
Stoppe 201451	Psoriasis	Fumaderm, 3 yr	Superficial malignant melanoma 3 yr before	Efalizumab 3 yr before	Grade 1–2	CD4+ T-cell defi- ciency (131/µl), CD4/CD8 ratio < 2	>2,000 copies/ ml CSF	Left-sided hemiataxia, dysarthria, unstable walking, no IRIS	Lesions in the left cerebellar peduncle, hemisphere and pons (Gd+)
Nieuwkamp 201553	Psoriasis	Psorinovo, 2 yr	None	None	Grade 1	Not given	Initially negative, positive during IRIS	Apraxia, progressive hemiparesis, somnolence, IRIS, fatal outcome	Multiple subcortical white matter lesions (Gd+), herniation
Rosenkranz 201528	Multiple sclerosis	Tecfidera, 4.5 yr	None	Glatiramer acetate	Grade 3	Not given	Positive	Severe gait and speech disorder, ataxia, fatal outcome	Confluent and progressive lesions in cerebellar peduncles, pons, and left cerebellar hemisphere
Hoepner 201552	Psoriasis	Fumaderm, 4 yr	None	Toxic bone marrow damage, increased excretion of kappa light chains	Grade 2	Not given	16 & 42 copies/ ml CSF	Right hemiparesis and aphasia, IRIS	Subcortical left hemispheric lesion
Current study	Psoriasis	Fumaderm, 2.5 yr	Adenocarcinoma in rectum (pT2 pN1 cM0 L0 V0) 8 yr earlier	Adjuvant radiochemotherapy with 5-fluorouracil 8 yr earlier	Grade 2	CD3+, CD4+, CD8+ T-cell defi- ciency, CD4/CD8 ratio < 2	Negative	Diplopia, nystagmus, dysphagia, dysarthria, tetraparesis (PG 3– 4), spasticity, ataxia, IRIS	Lesions in mesencephalon, pons, cerebellar pedunculi, and medulla oblongata (Gd+), right thalamus and subcortical lesions

Grade 3 lymphopenia, ALC < 500; grade 2, ALC = 500–799; grade 1, ALC = 800–1,000.¹ Fumaderm = 120mg dimethyl fumarate + 95mg of monoethyl fumarate); Psorinovo = dimethyl fumarate; Tecfidera = delayed-release dimethyl fumarate.

ALC = absolute lymphocyte count; CSF = cerebrospinal fluid; Gd⁺ = gadolinium-enhancing lesions; IRIS = immune reconstitution inflammatory syndrome; JCV = JC virus; MRI = magnetic resonance imaging; PCR = polymerase chain reaction; PG = paresis grade.