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Case report of a patient with progressive multifocal leukoencephalopathy under treatment with dimethyl fumarate.

Dammeier N, Schubert V, Hauser TK, Bornemann A, Bischof F - BMC Neurol (2015)

Bottom Line: She did not have antibodies against human immunodeficiency virus 1 and 2 and cerebrospinal fluid-polymerase chain reaction for viral infections including a sensitive JC-virus polymerase chain reaction were negative.Dimethyl fumarate was stopped and Mirtazapin and Mefloquin were initiated.Neurological examination and imaging remained stable.

View Article: PubMed Central - PubMed

Affiliation: University Tübingen, Center of Neurology and Hertie Institute for Clinical Brain Research, Hoppe-Seyler Strasse 3, 72076, Tübingen, Germany. nele.dammeier@uni-tuebingen.de.

ABSTRACT

Background: Progressive multifocal leukoencephalopathy is a severe demyelinating disease caused by the polyoma JC virus in patients with reduced immunocompetence. A few cases of progressive multifocal leukoencephalopathy have been reported in patients treated with fumaric acid esters.

Case presentation: A 53-year-old Caucasian woman reported to our clinic with a first focal epileptic seizure and mild cognitive impairment. Since 1.5 years, she was treated with fumaderm for her psoriasis. During that time, her lymphocyte counts ranged between 450 and 700/μl. Cerebral magnet resonance imaging showed multifocal subcortical T2 hyperintense lesions with partial gadolinium enhancement. She did not have antibodies against human immunodeficiency virus 1 and 2 and cerebrospinal fluid-polymerase chain reaction for viral infections including a sensitive JC-virus polymerase chain reaction were negative. The diagnosis of progressive multifocal leukoencephalopathy was established by histological analysis and detection of JC-virus desoxyribonucleic acid in brain biopsy specimens. Dimethyl fumarate was stopped and Mirtazapin and Mefloquin were initiated. Neurological examination and imaging remained stable.

Conclusions: Progressive multifocal leukoencephalopathy can occur in patients with lymphocyte counts between 450 and 700/μl, produce only faint symptoms and is not excluded by negative JC-virus-polymerase chain reaction in cerebrospinal fluid. The incidence of progressive multifocal leukoencephalopathy may thus be underestimated and a more careful surveillance of patients would be necessary.

No MeSH data available.


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Histological analysis of a brain biopsy from the right frontal lesion. (a) Enlarged nuclei containing viral inclusions (arrows). Hematoxylin and eosin. (b) Enlarged nuclei appear immunopositive when labeled with an antibody to JC-virus/SV40.
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Fig2: Histological analysis of a brain biopsy from the right frontal lesion. (a) Enlarged nuclei containing viral inclusions (arrows). Hematoxylin and eosin. (b) Enlarged nuclei appear immunopositive when labeled with an antibody to JC-virus/SV40.

Mentions: Cerebrospinal fluid (CSF) protein was slightly elevated (54 mg/l), cell count and IgG-Index were normal and she had identical oligoclonal bands in serum and CSF. She did not have antibodies against (Human immunodeficiency virus) HIV 1 and 2 and polymerase chain reaction (PCR) for JC-virus desoxyribonucleic acid (DNA) (University Tübingen (sensitivity of JC-virus DNA: > 1000 copies) and University Düsseldorf (sensitivity of JC-virus DNA: > 4 copies/assay [9]), Germany) of CSF was negative. Histological analysis of a biopsy of the right frontal lesion showed infiltration of lymphocytes, perivascular CD45-positive cells, CD68-positive microglia, reactive astrocytosis and focal demyelination (Fig. 2). Some cells had intranuclear inclusions and stained positive with an antibody against JC virus. PCR of brain tissue for JCV DNA was positive and confirmed the diagnosis of PML.Fig. 2


Case report of a patient with progressive multifocal leukoencephalopathy under treatment with dimethyl fumarate.

Dammeier N, Schubert V, Hauser TK, Bornemann A, Bischof F - BMC Neurol (2015)

Histological analysis of a brain biopsy from the right frontal lesion. (a) Enlarged nuclei containing viral inclusions (arrows). Hematoxylin and eosin. (b) Enlarged nuclei appear immunopositive when labeled with an antibody to JC-virus/SV40.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4495627&req=5

Fig2: Histological analysis of a brain biopsy from the right frontal lesion. (a) Enlarged nuclei containing viral inclusions (arrows). Hematoxylin and eosin. (b) Enlarged nuclei appear immunopositive when labeled with an antibody to JC-virus/SV40.
Mentions: Cerebrospinal fluid (CSF) protein was slightly elevated (54 mg/l), cell count and IgG-Index were normal and she had identical oligoclonal bands in serum and CSF. She did not have antibodies against (Human immunodeficiency virus) HIV 1 and 2 and polymerase chain reaction (PCR) for JC-virus desoxyribonucleic acid (DNA) (University Tübingen (sensitivity of JC-virus DNA: > 1000 copies) and University Düsseldorf (sensitivity of JC-virus DNA: > 4 copies/assay [9]), Germany) of CSF was negative. Histological analysis of a biopsy of the right frontal lesion showed infiltration of lymphocytes, perivascular CD45-positive cells, CD68-positive microglia, reactive astrocytosis and focal demyelination (Fig. 2). Some cells had intranuclear inclusions and stained positive with an antibody against JC virus. PCR of brain tissue for JCV DNA was positive and confirmed the diagnosis of PML.Fig. 2

Bottom Line: She did not have antibodies against human immunodeficiency virus 1 and 2 and cerebrospinal fluid-polymerase chain reaction for viral infections including a sensitive JC-virus polymerase chain reaction were negative.Dimethyl fumarate was stopped and Mirtazapin and Mefloquin were initiated.Neurological examination and imaging remained stable.

View Article: PubMed Central - PubMed

Affiliation: University Tübingen, Center of Neurology and Hertie Institute for Clinical Brain Research, Hoppe-Seyler Strasse 3, 72076, Tübingen, Germany. nele.dammeier@uni-tuebingen.de.

ABSTRACT

Background: Progressive multifocal leukoencephalopathy is a severe demyelinating disease caused by the polyoma JC virus in patients with reduced immunocompetence. A few cases of progressive multifocal leukoencephalopathy have been reported in patients treated with fumaric acid esters.

Case presentation: A 53-year-old Caucasian woman reported to our clinic with a first focal epileptic seizure and mild cognitive impairment. Since 1.5 years, she was treated with fumaderm for her psoriasis. During that time, her lymphocyte counts ranged between 450 and 700/μl. Cerebral magnet resonance imaging showed multifocal subcortical T2 hyperintense lesions with partial gadolinium enhancement. She did not have antibodies against human immunodeficiency virus 1 and 2 and cerebrospinal fluid-polymerase chain reaction for viral infections including a sensitive JC-virus polymerase chain reaction were negative. The diagnosis of progressive multifocal leukoencephalopathy was established by histological analysis and detection of JC-virus desoxyribonucleic acid in brain biopsy specimens. Dimethyl fumarate was stopped and Mirtazapin and Mefloquin were initiated. Neurological examination and imaging remained stable.

Conclusions: Progressive multifocal leukoencephalopathy can occur in patients with lymphocyte counts between 450 and 700/μl, produce only faint symptoms and is not excluded by negative JC-virus-polymerase chain reaction in cerebrospinal fluid. The incidence of progressive multifocal leukoencephalopathy may thus be underestimated and a more careful surveillance of patients would be necessary.

No MeSH data available.


Related in: MedlinePlus