Severe multiple sclerosis relapse under fingolimod therapy: Incident or coincidence?

Castrop, Florian; Kowarik, Markus C.; Albrecht, H.; Krause, M.; Haslinger, Bernhard; Zimmer, C.; Berthele, Achim; Hemmer, Bernhard

doi:10.1212/wnl.0b013e31824c46ad

Cited by 40 publications

(37 citation statements)

References 3 publications

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“…Development of these lesions indicates unusual activation of the immune system associated with FTY use. Table 1 summarizes some case reports where MS lesions were exacerbated after administration of FTY 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35. The heterogeneity of these cases regarding disease duration, prior therapy, time to relapse on FTY, neurological symptoms and so on might be related to interindividual differences among patients with a susceptible immune constitution and sensitivity to FTY.…”

Section: Fingolimod Induced White Matter (Tumefactive) Lesionsmentioning

confidence: 99%

Neurological safety of fingolimod: An updated review

Yoshii

Moriya

Ohnuki

et al. 2017

Clinical & Exp Neuroim

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Fingolimod (FTY) is the first oral medication approved for treatment of relapsing–remitting multiple sclerosis (RRMS). Its effectiveness and safety were confirmed in several phase III clinical trials, but proper evaluation of safety in the real patient population requires long‐term post‐marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000 MS patients, and there have been side‐effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders. In the present review, we focus especially on central nervous system adverse events. The topics covered are: (i) clinical utility of FTY; (ii) safety profile; (iii) post‐marketing adverse events in Japan; (iv) white matter (tumefactive) lesions; (v) rebound after FTY withdrawal; (vi) relationship between FTY and progressive multifocal leukoencephalopathy; (vii) FTY and progressive multifocal leukoencephalopathy‐related immune reconstitution inflammatory syndrome; and (viii) neuromyelitis optica and leukoencephalopathy.

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Section: Fingolimod Induced White Matter (Tumefactive) Lesionsmentioning

confidence: 99%

Neurological safety of fingolimod: An updated review

Yoshii

Moriya

Ohnuki

et al. 2017

Clinical & Exp Neuroim

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“…2 In our case, it was used during active disease. It was temporally associated with a worsening of the clinical condition culminating in tumefactive MS several years after initial disease onset.…”

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confidence: 91%

“…This observation confirms other case reports documenting the occurrence of atypical (tumefactive) demyelination 1 and multifocal inflammatory disease progression in patients with MS treated with fingolimod. [2][3][4] Disease progression might be initiated by a switch from natalizumab to fingolimod in some cases, 3,4 but also occurs in other situations, typically in the early stage of fingolimod treatment.…”

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confidence: 99%

Tumefactive multiple sclerosis lesions under fingolimod treatment

Kinney

Wattjes²,

McDonnell

et al. 2013

Neurology

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“…2 An association between fingolimod and tumefactive demyelination is further supported by reports of similar cases of patients with MS on fingolimod with tumefactive lesions, 3,4 in one case requiring craniectomy. 4 Possibly related are reports concerning a young woman with a severe MS relapse 5 and a man with neuromyelitis optica spectrum disorder with ex- , NAA slightly improves but remains low, due to neuro-axonal loss or damage, whereas creatine (Cr), myo-inositol (Ins), and Cho strongly increase due to glial proliferation. Lac has diminished, but Lip remains very prominent.…”

mentioning

confidence: 99%

Tumefactive multiple sclerosis lesions under fingolimod treatment

et al. 2012

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Fingolimod is an oral sphingosine 1-phosphate receptor modulator that prevents recirculation of lymphocyte subsets from lymph nodes. It decreases the number of relapses, slows the progression of disability, and improves MRI endpoints in patients with relapsing-remitting multiple sclerosis (RRMS).1 Infrequent but specific side effects are bradycardia, leukopenia, and macular edema.Case report. In November 2010, a 23-year-old woman with RRMS since September 2007 started fingolimod 0.5 mg per day in the setting of the openlabel FTY720D2316 trial. Interferon-␤ treatment was initiated in 2008, but discontinued mid-2010 because of side effects. Her disease course was relatively mild with low frequency and complete recovery of relapses. In March 2011, she presented with a left-sided hemiparesis, headache, and nausea that had gradually developed over 2 weeks. Because she had no clinical signs of infection, an exacerbation of multiple sclerosis (MS) was considered initially and she was admitted for IV methylprednisolone treatment. During the administration of the first dosage, the hemiparesis progressed and she had 2 partial epileptic seizures with jerks of the left leg, 1 of which generalized. We discontinued methylprednisolone and fingolimod and started valproic acid and acyclovir. New demyelinating lesions, infection (herpes or varicella encephalitis, toxoplasmosis, or brain abscess), and neoplasm (lymphoma, glioma) were considered to be possible causes of her symptoms.Cranial MRI showed 2 large white matter lesions in the right hemisphere with surrounding vasogenic edema, mass effect, and open ring enhancement after gadolinium administration (figure, A). This suggested multifocal tumefactive demyelination, which was supported by magnetic resonance spectroscopy ( figure, B-D). A pyogenic abscess was unlikely because of absence of diffusion restriction.Serologic studies were negative for syphilis, Borrelia, HIV, and toxoplasmosis; and cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV) were all immunoglobulin G positive and immunoglobulin M negative. In the CSF we found 7 leukocytes/L (0-4), glucose 3.5 mmol/L (serum glucose 6.4 mmol/L), protein 1,065 mg/L (0 -500). No pathologic cells were found in the CSF. CSF cultures for bacteria, mycobacteria, yeast, and fungus were negative. CSF PCR for mycobacteria, CMV, EBV, HSV-1, HSV-2, VZV, and JCV was negative.We discontinued treatment with acyclovir after viral PCRs returned negative. The patient recovered within 1 week and was discharged with a slight residual left-sided hemiparesis.In the weeks after discharge she recovered completely. We performed serial follow-up MRI, showing gradual regression and remyelination of the lesions. Discrete areas of focal demyelination remained. One month after discharge, small new gadolinium-enhancing lesions were seen, indicating new inflammatory MS activity ( figure, A). This led us to start glatiramer acetate.Discussion. Tumefactive demyelination refers to demyelinating brain le...

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Severe multiple sclerosis relapse under fingolimod therapy: Incident or coincidence?

Cited by 40 publications

References 3 publications

Neurological safety of fingolimod: An updated review

Neurological safety of fingolimod: An updated review

Tumefactive multiple sclerosis lesions under fingolimod treatment

Tumefactive multiple sclerosis lesions under fingolimod treatment

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