European Journal of Neurology 2011, 18: e110e111

doi:10.1111/j.1468-1331.2011.03430.x

LETTER TO THE EDITOR

Could antiretroviral drugs be effective
in multiple sclerosis? A case report
H. Maruszaka, B. J. Brewb, G. Giovannonic and J. Golda
a

Albion Street Centre, Surry Hills, Sydney;

Department of Neurology and St Vincents
Centre for Applied Medical Research,
National Centre in HIV Epidemiology and
Clinical Research, St Vincents Hospital,
Darlinghurst, Sydney, Australia; and
c
Blizard Institute of Cell and Molecular
Science, Queen Mary University of
London, Barts and The London School of
Medicine and Dentistry, London, UK.
b

Correspondence: Dr Hubert Maruszak,

Albion Street Centre HIV Clinic, 150-154
Albion Street, Sydney, NSW 2010,
Australia (tel.: +61 (2) 93329690; fax:
+61 (2) 93324219; e-mail: hubert.
maruszak@sesiahs.health.nsw.gov.au).
Keywords: antiretroviral therapy, human
immunodeciency virus, multiple sclerosis, treatment
Received 17 February 2011
Accepted 8 April 2011
Sir,
In 1985, a 26-year-old Caucasian man
presented with an acute onset of neuro-

logical illness over 1 week, manifesting as

bilateral blindness, paresthesiae and
weakness on his left side, deafness and
paresis of the left side of his tongue.
Bilateral optic neuritis and left-sided
hemiparesis, conductive deafness, hip
exor weakness, bilateral extensor plantar
responses and a positive Rombergs sign
were found on neurological examination.
Visual evoked responses at admission
showed abnormally delayed responses
through both eyes.
Cerebrospinal uid (CSF) analysis
revealed minimal lymphocytes, intrathecal
synthesis of oligoclonal IgG bands, normal glucose and protein and no growth on
culture. The brain CT scan was within
normal limits. There was no family history
of multiple sclerosis (MS). In December
1985, the patient was reviewed by several
neurologists with the consensus diagnosis
of relapsingremitting MS. It was
suggested that the MS may have been
triggered by the acute HIV infection
experienced by the patient several months
before. Over the following 2 years he had
three relapses, consisting of transitory
bilateral blindness with central scotomata,
urinary and faecal incontinence and
hemiparesis, all of which responded to
intravenous corticosteroids. A repeat CSF
analysis in May 1986 showed presence of
lymphocytes (10/mm3), intrathecal synthesis of oligoclonal IgG bands, raised

IgG 8.4 mg%, Alb 21 mg% and negative

serology for herpes simplex virus, mumps,
measles, CMV and syphilis. A repeat
electroencephalograph (EEG) and brain
CT were normal. The patient started on
interferon beta, but the treatment was
promptly ceased because of side eects.
Over the next 10 years, he had worsening
urinary incontinence and faecal
incontinence, to the extent that he used
pads at night. Urodynamic studies
conrmed a spastic bladder which
was treated with oxybutynin. Motor
function was preserved, and there was
only slowing of working memory without
progression.
Several months after his rst acute
neurological illness in 1985, this patient
was also found to be HIV positive. He had
a history of a severe u-like illness consistent with an HIV seroconversion illness.
Over the past 25 years, he has not had any
AIDS dening conditions or signicant
complications from HIV infection. During
the rst 10 years of his HIV infection, his
immune function was reasonably stable
with average CD4 T cell count above
400 cells/ml and median HIV RNA viral
load of 19 000 copies/ml. In 1996, he
started highly active antiretroviral therapy
(HAART) and over the following 14 years
was on various drug combinations presented in Table 1. Whilst on HAART he
maintained an undetectable (<50 copies/

Table 1 Time-line of antiretroviral regimens, drug and regimen-combined CNS penetration-effectiveness score (CPE), HIV RNA viral load, CD4
cells count and relapsingremitting symptoms

ND, no data available.

a
CPE Score central nervous system penetration-effectiveness score; 1.0, highest penetration; 0.5, intermediate penetration; 0.0, lowest penetration.

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2011 The Author(s)

European Journal of Neurology 2011 EFNS

Letter to the Editor

ml) serum and CSF HIV RNA viral load
and CD4 count of between 480890 cells/
ml.
Within months of commencing HAART, all MS symptoms gradually improved. Within 2 years, his urinary
incontinence was controlled to the extent
that he stopped using pads and faecal
incontinence resolved. He has had no MS
relapses.
A gadolinium-enhanced magnetic
resonance image of the brain carried out
6 years after the commencement of
HAART showed small focal high T2
signal areas in parietal and frontal
periventricular white matter, indicative
of MS. At the same examination, his
repeated visual evoked responses were
now reported as being within the normal
range.
To our knowledge, this is the rst case
of a patient diagnosed with MS treated
with HAART with sustained resolution of
MS decits.
The diagnosis of MS was supported by
the fact this patient had three documented
clinical relapses and had intrathecal
synthesis of oligoclonal IgG bands in the
CSF, although the latter may occur in
HIV disease. Furthermore, recurrent

bilateral optic neuritis with hemiparesis,

spastic bladder and faecal incontinence
responding to corticosteroids are not
consistent with HIV infection in patients
with relatively preserved immune function. Whilst acknowledging the limitations
of our retrospective case review, we speculate that HAART may have alleviated
the progressive course of MS and resulted
in clinical remission, especially as the
HAART regimen used had good penetration into the central nervous system.
An MS-like illness has been previously
described in association with HIV-1
infection. Berger and colleagues described
seven men with HIV-1 infection with a
clinical syndrome indistinguishable from
MS [1]. Interestingly, as the immunodeciency caused by HIV-1 infection progressed in their patients the MS remained
active with ongoing relapses. Whether this
syndrome represents a dierent disease
entity, as has been described previously by
Corral et al., is a moot point [2]. Our
patient and the seven patients described by
Berger et al. raise some interesting
hypotheses about the pathogenesis of
MS with important implications for the
treatment. This has relevance to the
unresolved issue of the relationship be-

2011 The Author(s)

European Journal of Neurology 2011 EFNS European Journal of Neurology 18, e110e111

e111

tween human endogenous retrovirus

infection (HERV) and MS where HAART
can inuence HERV expression and possibly ameliorate MS [3]. It should be noted
that MS aetiology is still unknown and
may be heterogeneous; thus, the relevance
of our observations may be restricted to
HIV-positive patients. Further clinical
investigations in MS population are warranted.
References
1. Berger JR, Sheremata WA, Resnick L,
Atherton S, Fletcher MA, Norenberg M.
Multiple sclerosis-like illness occurring with
human immunodeciency virus infection.
Neurology 1989; 39: 323329.
2. Corral I, Quereda C, Garc a-Villanueva M,
et al. Focal monophasic demyelinating leukoencephalopathy in advanced HIV infection.
Eur Neurol 2004; 52: 3641.
3. Contreras-Galindo R, Almodovar-Camacho
S, Gonzalez-Ram rez S, Lorenzo E,
Yamamura Y. Comparative longitudinal
study of HERV-K and HIV-11 RNA titers in
HIV-1 infected patients receiving successful
versus unsuccessful highly active antiretroviral therapy. AIDS Res Hum Retroviruses
2007; 23: 10831086.