Download Correspondence - VIROLOGIA-Pisa

15 JANUARY
Correspondence
5-HT2a Inhibitors for
Progressive Multifocal
Leukoencephalopathy: Old
Drugs for an Old Disease
To the Editor—In the 1 September 2007
issue of the Journal, Verma et al. show that
mirtazapine arrested progressive multifocal leukoencephalopathy (PML) in a patient with polycythemia vera [1]. Although this is the first reported case of
PML in a patient with polycythemia vera,
it is not a first regarding the effectiveness
of 5-HT2a antagonists against PML. Actually, after the seminal article by Elphick et
al. was published in 2004 [2], we speculated on the possible use of clinically approved antipsychotic drugs for PML [3].
In 2006, our group showed the effectiveness of risperidone (8 mg/day for 10 days)
in a 33-year-old haploidentical stem-cell
transplant recipient with PML refractory
to intravenous cidofovir and donor lymphocyte infusions [4]. We also recently
suggested schedules for PML treatment
with risperidone, ziprasidone, and olanzapine [5].
Mirtazapine is also not a first for PML
treatment. In 2006, Vulliemoz et al. [6]
first showed the effectiveness of a 5-day
course of intravenous cytarabine (2 mg/
kg/day for 5 days) and an ongoing treatment of mirtazapine at 30 mg/day in
a 44-year-old HIV-negative male with
dermatomyositis and PML. In 2007,
Owczarczyk et al. [7] also showed successful treatment of PML in a 58-year-old
white woman after 6 infusions of cidofovir and mirtazapine at 15 mg/day starting
after the second infusion of cidofovir.
Our group also proposed the monitoring
of drops in JC viruria by psychoactive
drugs as a surrogate marker for comparing the effectiveness of different 5-HT2a
inhibitors against PML [8].
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JID 2008:197 (15 January)
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We read with interest that the patient
reported by Verma [1] et al. had positive
JC viremia at diagnosis of PML. In both
our HIV-negative PML patients and in
the PML patients who received natalizumab [9], JC viremia was usually positive before the onset of symptoms [4]
while being normally absent in healthy
control subjects and transplant recipients.
It is also a far less invasive and expensive
test than stereotactic biopsy.
These findings also imply that JC virus
replication can be 5-HT2a dependent even
outside the central nervous system, soliciting investigations for 5-HT2a–positive
competent cell types (e.g., white blood
cells) that could easily be cultivated, in
contrast to adult glial cells.
5.
6.
7.
8.
9.
1,a
4,a
Daniele Focosi, Richard Eric Kast,
Fabrizio Maggi,2 Giuseppe Lauria,3
Luca Ceccherini-Nelli,2 and Mario Petrini1
1
Department of Oncology, Transplants, and
Advances in Medicine, Division of Hematology, and
2
Virology Section and Retrovirus Center, Department
of Experimental Pathology, University of Pisa, Pisa,
and 3Neuromuscular Diseases Unit, National
Neurological Institute “Carlo Besta,” Milan, Italy;
4
Department of Psychiatry, University of Vermont,
Burlington
ment with risperidone. Antiviral Res 2006; 74:
156 – 8.
Kast RE, Focosi D, Petrini M, Altschuler EL.
Treatment schedules for 5-HT2A blocking in
progressive multifocal leukoencephalopathy
using risperidone or ziprasidone. Bone Marrow Transplant 2007; 39:811–2.
Vulliemoz S, Lurati-Ruiz F, Borruat F, et al.
Favourable outcome of progressive multifocal
leucoencephalopathy in two patients with dermatomyositis. J Neurol Neurosurg Psychiatry
2006; 77:1079 – 82.
Owczarczyk K, Hilker R, Brunn A, Hallek M,
Rubbert A. Progressive multifocal leucoencephalopathy in a patient with sarcoidosis—successful treatment with cidofovir and mirtazapine. Rheumatology (Oxford) 2007; 46:888 –90.
Focosi D, Kast RE, Maggi F, Ceccherini-Nelli
L, Petrini M. Risperidone-induced reduction
in JC viruria as a surrogate marker for efficacy
against progressive multifocal leukoencephalopathy and hemorrhagic cystitis. J Clin Virol
2007; 39:63– 4.
Van Assche G, Van Ranst M, Sciot R, et al.
Progressive multifocal leukoencephalopathy
after natalizumab therapy for Crohn’s disease.
N Engl J Med 2005; 353:362– 8.
Potential conflicts of interest: none reported.
a
D.F. and R.E.K. contributed equally to this letter.
Reprints or correspondence: Dr. Daniele Focosi, Dept. of
Oncology, Transplants, and Advances in Medicine, Div. of
Hematology, University of Pisa, via Roma 56, 56100 Pisa,
Italy ([email protected]).
The Journal of Infectious Diseases 2008; 197:328
© 2008 by the Infectious Diseases Society of America. All
rights reserved. 0022-1899/2008/19702-0023$15.00
DOI: 10.1086/524877
References
1. Verma S, Cikurel K, Koralnik IJ, et al. Mirtazapine in progressive multifocal leukoencephalopathy associated with polycythemia vera.
J Infect Dis 2007; 196:709 –11.
2. Elphick GF, Querbes W, Jordan JA, et al. The
human polyomavirus, JCV, uses serotonin receptors to infect cells. Science 2004; 306:1380 –3.
3. Altschuler E, Kast R. The atypical antipsychotic agents ziprasidone [correction of zisprasidone], risperdone and olanzapine as
treatment for and prophylaxis against progressive multifocal leukoencephalopathy. Med
Hypotheses 2005; 65:585– 6.
4. Focosi D, Fazzi R, Montanaro D, Emdin M,
Petrini M. Progressive multifocal leukoencephalopathy in a haploidentical stem cell
transplant recipient: a clinical, neuroradiological and virological response after treat-
CORRESPONDENCE
Reply to Focosi et al.
To the Editor—We read with interest Focosi et al.’s letter [1] in response to our
brief report on the role played by mirtazapine in the treatment of progressive multifocal leukoencephalopathy (PML). Although we appreciate the comments, it
should be clarified that our article did not
claim to be the first report of the potential
role of 5-HT2a blockers in the treatment of
PML. Our aim was rather to document
and highlight the clinical, virological, and
radiological improvement in our patient
with PML in polycythemia vera. Furthermore, most of the references cited by Focosi et al. were published after our report
was submitted [2–5] or were written by
one of our coauthors [6].
Focosi et al. note that the diagnosis of
PML could have been established on the
basis of the detection of JC virus (JCV)
DNA in the blood by polymerase chain
reaction (PCR) instead of by performing a
brain biopsy. The established diagnosis of
PML in our patient was based on the brain
biopsy performed at another institution
before her arrival at our medical center
and before PML was considered as a possible diagnosis. Furthermore, JC viremia
is present in 16%–38% of immunosuppressed individuals who do not have
PML, and JCV PCR is positive in the
blood of only 70%– 80% patients with
PML [7–10].
Susama Verma,1 Katia Cikurel,1
Igor J. Koralnik,6 Susan Morgello,2
Charlotte Cunningham-Rundles,3
Zelig R. Weinstein,4 Christine Bergmann,5 and
David M. Simpson1
Departments of 1Neurology, 2Pathology,
3
Immunobiology, 4Neuroradiology, and 5Psychiatry,
The Mount Sinai Medical Center, New York, New
York; 6HIV/Neurology Center, Beth Israel Deaconess
Medical Center, Harvard Medical School, Boston,
Massachusetts
References
5. Focosi D, Kast RE, Maggi F, Ceccherini-Nelli
L, Petrini M. Risperidone-induced reduction
in JC viruria as a surrogate marker for efficacy
against progressive multifocal leukoencephalopathy and hemorrhagic cystitis. J Clin Virol
2007; 39:63– 4.
6. Vulliemoz S, Lurati-Ruiz F, Borruat F, et al.
Favourable outcome of progressive multifocal leucoencephalopathy in two patients with
dermatomyositis. J Neurol Neurosurg Psychiatry 2006; 77:1079 – 82.
7. Tornatore C, Berger JR, Houff SA, et al. Dectection of JC virus DNA in peripheral lymphocytes from patients with and without
progressive multifocal leukoencephalopathy.
Ann Neurol 1992; 31:454 – 62.
8. Dubois V, Lafon ME, Ragnaud JM, et al. Detection of JC virus DNA in peripheral blood
leukocytes of HIV-infected patients. AIDS
1996; 10:353– 8.
9. Ferrante P, Caldarelli-Stefano R, OmodeoZorini E, et al. Comprehensive investigation of the presence of JC virus in AIDS
patients with and without progressive
multifocal leukoencephalopathy. J Med Virol 1997; 52:235– 42.
10. Koralnik IJ, Boden D, Mai VX, Lord CI,
Letvin NL. JC virus DNA load in patients
with and without progressive multifocal leukoencephalopathy. Neurology 1999; 52:253–
60.
Potential conflicts of interest: none reported.
Financial support: Public Health Service (grants R01 NS/AI
041198 and NS 047029 to I.J.K. and NS002253 to D.M.S.);
Ellen R. Cavallo Research Fund; National Institutes of Health
(grant R24MH59724 to S.M. and D.M.S.).
Reprints or correspondence: Katia Cikurel, 200 E. 69th St.,
New York, NY 10021 ([email protected]).
The Journal of Infectious Diseases 2008; 197:328 –9
© 2008 by the Infectious Diseases Society of America. All
rights reserved. 0022-1899/2008/19702-0024$15.00
DOI: 10.1086/524876
1. Focosi D, Kast RE, Maggi F, Lauria G,
Ceccherini-Nell L, Petrini M. 5-HT2a inhibitors for progressive multifocal leukoencephalopathy: old drugs for an old disease. J Infect
Dis 2008; 197:328 (in this issue).
2. Focosi D, Fazzi R, Montanaro D, Emdin M,
Petrini M. Progressive multifocal leukoencephalopathy in a haploidentical stem cell
transplant recipient: a clinical, neuroradiological and virological response after treatment with risperidone. Antiviral Res 2007;
74:156 – 8.
3. Kast RE, Focosi D, Petrini M, Altschuler EL.
Treatment schedules for 5-HT2A blocking in
progressive multifocal leukoencephalopathy
using risperidone or ziprasidone. Bone Marrow Transplant 2007; 39:811–2.
4. Owczarczyk K, Hilker R, Brunn A, Hallek
MR, Rubbert A. Progressive multifocal leukoencephalopathy in a patient with sarcoidosis—successful treatment with cidofovir
and mirtazapine. Rheumatology (Oxford)
2007; 46:888 –90.
CORRESPONDENCE
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JID 2008:197 (15 January)
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