associated myelopathy in Argentina
FURTHER STUDIES ON HTLV-I ASSOCIATED MYELOPATHY IN ARGENTINA
LEONARDO A. GONZALEZ,
ANDRES M. VILLA, GUILLERMO KOHLER, ORLANDO GARCEA, MARCELO
KREMENCHUTZKY, FERNANDO CACERES, OLGA P. SANZ, ROBERTO E. P. SICA
Hospital Ramos Mejía, Buenos Aires
Key words: HTLV-I associated myelopathy, tropical spastic
report 10 HTLV-I virus seropositive subjects, eight of them with
HTLV-I associated myelopathy (HAM), two of them also infected
with HIV as well as two asymptomatic HTLV-I+ relatives of two
unrelated patients. HTLV-I is endemic in several tropical areas, where
it causes different neurological diseases. Only few patients have been
reported in our country since 1994. We studied 8 patients, who
fulfilled the clinical criteria for chronic spastic paraplegia, and 2
other non-symptomatic HTLV-I seropositive relatives, with
electromyography (EMG), motor and sensory conduction velocities (NCV),
somatosensory, visual and brainstem auditory evoked potentials (SSEP,
VEP and BAEP), Magnetic Resonance Images (MRI) and cerobrospinal fluid
(CSF) analysis. The latter was carried out only in seven symptomatic
patients. In every case positive ELISA tests for HTLV-I/II were
confirmed by Western Blot. The two asymptomatic persons were
clinically and electromyographically assessed, one of them was also
submitted to SSEPs studies. Three patients were males. Patient’s
ages ranged from 5 to 65 years old. All symptomatic patients showed
muscular weakness, spasticity with pyramidal signs and sphincter
disturbances. Five of them had paresthesias and 2 had burning pain on
their feet. The EMGs and the NCVs were normal in 7 patients and in the
2 asymptomatic ones. SSEPs, obtained by stimulating the posterior
tibial nerves, were impaired in 7 patients and in the asymptomatic
person who received the procedure. The 7 symptomatic patients who
underwent lumbar puncture had positive tests for HTLV-I in CSF, 3 out
of these 7 patients had also high protein levels and 4 had increased
number of lymphocytes. In 2 patients intrathecal IgG production could
also be demonstrated. MRI were normal in 7 patients and in the 2
asymptomatics, the exception being a female who had bilateral
hyperintense lesions in cerebral white matter in T2. In conclusion,
tropical spastic paraparesis is apparently a rare disorder in
Argentina. However, some cases have been reported recently. Most
probably, its prevalence is currently underestimated. Its diagnosis
should be considered in every patient with progressive spastic
estudios sobre mielopatía asociada a HTLV-I en la Argentina.
Presentamos 10 pacientes con serología positiva para HTLV-I, 8 de
ellos con mielopatía asociada a HTLV-I (HAM), incluyendo 2 HIV
positivos. El HTLV-I es endémico en varias áreas tropicales, donde
es responsable de diferentes patologías. En nuestro país fueron
comunicados unos pocos pacientes desde 1994 (Garcea et al 1994;
Gutfraind et al 1995; Micheli et al 1996). Estudiamos 8 pacientes con
paraplejía crónica progresiva, y dos familiares directos
seropositivos asintomáticos, con electromiografía (EMG), velocidades
de conducción motora y sensitiva (VC), potenciales evocados
somatosensitivos, visuales y auditivos (PESS, PEV y PEAT), Imágenes
de Resonancia Magnética (IRM) y estudio del líquido cefalorraquídeo
(LCR). La punción lumbar (PL) fue hecha sólo en 7 de los 8 pacientes
sintomáticos. Todos los resultados de ELISA positivos para el HTLV-I
fueron confirmados con Western Blot. Tres pacientes eran hombres. Los
pacientes tenían entre 5 y 65 años de edad. Todos los pacientes
sintomáticos presentaban debilidad muscular, espasticidad,
piramidalismo y trastornos esfinterianos. Cinco tenían parestesias y
2 dolor urente en los pies. Los EMGs y VCs fueron normales en 9,
mientras que los PESS estimulando los nervios tibiales posteriores
fueron anormales en 8 pacientes. Los 7 pacientes sintomáticos a los
que se les realizó PL tuvieron serología positiva para HTLV-I en
LCR, en 3 de ellos se demostró hiperproteinorraquia y en 4
pleocitosis linfocítica. Además, en 2 se pudo demostrar la
producción intrathecal de IgG. Las IRM fueron normales en 9
pacientes, siendo la excepción una paciente con imágenes
hiperintensas en sustancia blanca en secuencias de T 2. En
conclusión, la paraparesia espástica tropical es aparentemente una
enfermedad rara en nuestro país. Aunque últimamente se han estado
comunicando algunos casos, probablemente su prevalencia es
subestimada. Destacamos la importancia de la inclusión de este
diagnóstico en todo paciente con paraplejía espástica progresiva.
Postal address: Dr. Roberto E. P. Sica, División
Neurología, Hospital Ramos Mejía, Urquiza 609, 1221 Buenos Aires,
Argentina. Fax: 54-1-962-2022
Received: 31-III-1998 Accepted: 3-VI-1998
Chronic progressive myelopathy is defined as a para-plegia with
gradual onset and variable levels of sensory loss and sphincter
disturbances, without evidences of lower motor neuron involvement,
spinal cord com-pression, or supramedullary disseminated lesions1-5.
This disease has usually been reported in high HTLV-I endemic areas;
mainly the Caribbean, Southern Japan, Central and South America6-11.
In Argentina, as far as we know, surveys done in blood donors in
Buenos Aires yielded a low prevalence, similar to that of non ende-
mic countries12, 13. We report our experience in 8 cases of slowly
progressing spastic paraplegia, with positive HTLV-I antibodies in
sera and cerebrospinal fluid (CSF) and in two non-symptomatic
relatives, also infected with the mentioned retrovirus. Because in
Argentina, HAM/TSP is not a frequently reported illness14, 15, the aim
of this work is to present epidemiologic data and the clinical
features, the neurophysiology, the imaging and the CSF findings in
this group of patients.
Material and Methods
Altogether we studied 8 patients, 6 females and 2 males, aged
between 24 and 65 years, who fulfilled the clinical criteria for
chronic spastic paraplegia (#1 to #8). Once the diagnosis was made, we
summoned the patient’s relatives and made a serological screening
looking for HTLV-I subclinical infection. We could only assess 4
relatives and found two of them (#9 and #10) who disclosed positive
serological tests. Those two persons were investigated through
clinical and laboratory studies and included within this
communication. The rational for doing this is to show that some
findings can be achieved in people who may have the infection but
remain clinically asymptomatic.
Electromyography (EMG) and nerve conduction studies (NCV) were
performed in every patient and in the asymptomatic persons,
somatosensory evoked potentials (SSEP) were carried out in 9 subjects
including one of the asymptomatic persons, brainstem auditory evoked
potentials (BAEP) were investigated in 7 patients and visual evoked
potentials (VEP) in the 8 patients. Brain and cervical spinal cord
magnetic resonance images (MRI) were obtained in all symptomatic
subjects. Blood profiles were analyzed in every subject. Lumbar
puncture was performed in 7 symptomatic patients, and CSF glucose,
proteins, and cell content were determined. Immunoglobulin G and
oligoclonal bands were searched for in 3 patients. The presence of IgG
antibodies against HTLV-I was always confirmed by Western Blot. CSF
and serum VDRL were studied in every patient who received lumbar
Epidemiologic data: Three patients were from northern provinces,
located within the subtropical regions of the Country, 5 patients were
in downtown Buenos Aires and currently living in the city. Two
patients were also infected with HIV, (intravenous drug abusers).
Another patient had had blood transfusion several years before the
beginning of the symptoms. Two out of the four relatives investigated
had positive serological tests, and were the wife and one son of two
different symptomatic patients; these two persons were born in Buenos
Aires and lived there at the time of their assessment.
Clinical Features. (Table 1). Patients were aged between 24 and 65
years. Symptomatic patients had muscular weakness in both lower limbs,
without atrophy, but with moderate to severe spasticity and sphincter
disturbances. Sensory symptoms, described as paresthesias or
hypoesthesias, were frequently found, 2 patients also had burning pain
on their feet. Onset of their complaints at the time of their clinical
aseessment ranged from 5 months to 30 years; the shortest interval was
observed in one female patient who also was HIV infected. Monoparesis
was the first symptom in 4 patients and bladder dysfunction in one.
Ashworth score16 was 4/5 in 5 patients, 3/5 in 1 and 2/5 in the
remaining 2. The asymptomatics were 40 and 5 years old. (Table 1).
CSF Findings. All patients studied had normal glucose, negative VDRL
reaction, and positive tests for antibodies against HTLV-I.
Lymphocytic pleocytosis was found in 4 patients and intrathecal IgG
was elevated in 2 out of 3 patients tested. We did not perform lumbar
tap in the asymptomatics.
Neurophysiology. All patients and the asymptomatic subjects had normal
EMGs and motor and sensory NCVs, except patient #7 who lacked muscle
response when stimulating the right peroneal nerve. VEPs were
bilaterally prolonged only in 1 patient (#2), while BAEPs showed a
prolonged I-III conduction time in 1 patient (#2) and could not be
obtained in another (#4). Finally, SSEPs were impaired in 7 patients
out of the 8 tested. The asymptomatic subject who received this
procedure also showed impairment of this evoked potential. We studied
only one limb because there were no clinical differences between right
and left lower limbs. (Table 2).
Images. Only 1 out of the 8 patients had brain MRI abnormal findings
consisting of non-specific high-signal white matter lesions in T2
sequences. The other patients had normal brain and cervical spinal
As previously described in the literature5 our patients had the
typical clinical picture of gradual onset spastic paraplegia with
pyramidal signs, developing, in the course of the illness, sphincter
disturbances. Intrathecal IgG synthesis and elevated IgG index have
been described in most patients reported in the literature17, 18; we
could document these features only in 2 subjects of our se-ries.
Peripheral nervous system involvement has been described in the
literature in about 25% of the pa- tients5, 19, in our series we only
found one patient with focal abnormal NCVs studies in one of her lower
limbs. In the literature, abnormal VEP latencies were seen in 30% of
the patients, and BAEPs prolonged latencies were also found in 25% of
them5, 20. We found only one patient with abnormal VEPs latencies and
2 who showed abnormal BAEPs.
Although lower limbs SSEPs had delayed latencies in 7 of the 8
patients who were tested and in the asymp-tomatic subject who was
submitted to the procedure, the figures obtained bore no relationship
with the severity of their clinical involvement. Pathologic findings
in brain images have been described in almost 60% of the patients by
other authors5, 19; we found non-specific high-signal white matter
lesions in T2 sequences in only one patient. All the spinal MRI were
normal, including the one belonging to the patient who showed brain
It can be concluded that HAM/TSP is a rare disorder in our country
although some cases have been reported in recent years14, 15.
Probably, its prevalence is currently underestimated. Its diagnosis
should be considered in every patient with progressive spastic
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TABLE 1.– Clinical features
Patient Onset Time from Paraparesis ASS. Sph. D. Sen. D. Pain
#1 RL 5 years Moderate 4/5 Yes No No
#2 RL 2 years Severe 4/5 Yes Paresthesia No
#3 Paraparesis 4 years Moderate 4/5 Yes Paresthesia Yes
#4 Pain+RL 9 months Moderate 4/5 Yes Paresthesia Yes
#5 Urinary retention 10 years Mild 3/5 Yes No No
#6 Paraparesis 11 years Moderate 4/5 Yes Paresthesia No
#7 Paraparesis 30 years Moderate 2/5 Yes No Yes
#8 LL 5 months Mild 2/5 Yes No No
#9 No - No 1/5 No No No
#10 No - No 1/5 No No No
RL: right leg; LL: left leg; ASS: Aschworth spasticity score;
Sph. D.: Sphincter disturbances; Sen. D.: Sensory disturbances
Note: All the symptomatic patients had pyramidal signs but none had
TABLE 2.– Lower limbs SSEPs latency and amplitude values
N (ms) P (ms) Ampl (µV)
#1 49 53 1,5
#2 No response No response No response
#3 No response No response No response
#4 59 64,4 3,75
#5 38 40 3
#6 No response No response No response
#7 No response No response No response
#8 46 52 2,50
#9 48 53 2
#10 ND ND ND
Normal ranges: N: 32-34 ms; P: 40-42 ms; Ampl: > 1,25 µV
ND: not done