Download Clinical Characteristics of Iranian Patients With HTLV

Clinical Characteristics of Iranian Patients
With HTLV-I Associated Myelopathy (HAM)
*Dr Arami MA, MD
** Dr Kholghi Y, MD
*Consultant neurologist of Milad hospital _Tehran **Consultant neurologist of Rasool-Akram hospital_Guilan_Rasht
Abstract: Background: Human T lymphotropic virus type 1 myelopathy (HAM) that
previously named tropical spastic paraparesis (TSP) is one of the major causes of infectious
myelopathy in some area of the world. The epidemiology of the HAM in Iran is not clear in
all geographic regions. This study explains some of clinical characteristics of a group of
Iranian patients with HAM that referred from many provinces (against previous studies in
Iran). Methods and materials: All suspected cases of HAM that referred to our hospitals
from 2000 through 2006 and tested for HTLV-1 serology were reviewed. All selected
patients with positive laboratory results were evaluated by expert neurologists. Brain and
spinal cord MRI, EMG/NCV, somatosensory evoked potentials (SSEP) and CSF examinations
were done for all patients. Past medical history and also demographic and clinical
characteristics of patients were analyzed and compared with characteristics of patients of
other countries. Results: Among 25 evaluated patients, females have been affected
significantly more than males (64% against 36%) and the mean age at HAM onset was
(33.3±14.6 y). The most common symptoms and signs were; spasticity and hyperreflexia (in
all patients), lower limb paresthesia (68%), urinary complaints (92%), and lumbar pain
(12%). Constipation was not frequent and the most common form of bladder involvement
was neurogenic spastic bladder presented with frequency. Sensory level, pathologic
cerebellar signs and tremor were detected in a few cases. Nearly all patients had breast
feeding in their neonatal period but blood transfusion had been done in 5 cases (20%).
Positive familial history of paraparesis was found only in 1 patient. Conclusions: Recently,
HAM is frequently diagnosed in our country in a wide area. Special clinical and
epidemiological characteristics could be studied and some preventive measures must be
considered and the prime cause of female preponderance in middle or childbearing age
could be obviated.
Key words: Clinical Characteristics- Human T-Lymphotropic Virus Type-1 Associated
Myelopathy (HAM)-Iranian patients.
Introduction: In 1888, Strachan’s paper published on Jamaican peripheral neuritis. In 1956,
Cruikshank described patients with spasticity (tropical spastic paraparesis, TSP) which he
termed Jamaican neuropathy. In 1985, Gessain and colleagues, investigating the
seroprevalence of HTLV-I among hematology patients and found that 59% of patients with
tropical spastic paraparesis had anti-HTLV-I antibodies. In Japan, where adult T cell leukemia
was first described in 1977 and associated with HTLV-I in 1981.Osame et al described the
association of HTLV-I with a spastic paraparesis which they called HTLV-I associated
myelopathy (HAM). While seronegative TSP has been described, by definition all patients
with HAM are infected with HTLV-I.HTLV-I and the related virus, HTLV-II, are transmitted by
sexual intercourse, especially from males to females. Parenterally through cellular blood
products and the reuse of injecting equipment. From mother to child, predominantly
through breast feeding. Although Europe is not an endemic area for HTLV-I infection, it is
found among immigrants from high prevalence areas, their partners, and sporadically in the
native population. HTLV-II is common among intravenous drug users in a number of
European cities.
There are three main hypotheses for Pathogenesis:
1. Direct toxicity
2. Autoimmunity
3. Bystander damage
Direct toxicity hypothesis: HTLV-I infects glial cells in vivo, which then present HTLV-I
antigens on their cell surface. Circulating CD8+ cytotoxic T cells specific for a HTLV-I antigen
cross the blood–brain barrier, encounter the infected cell, and release cytokines which
cause cell death.
Autoimmune hypothesis: Glial cells “self” antigen is similar to a viral antigen. CD4+ helper
cells encounter this viral antigen in the periphery and upon crossing the blood–brain barrier,
mistake the glial cell for an infected cell triggering autoimmune activity with death of the
glial cell. Alternatively, CD4+ “helper” cells which by chance recognize “self” antigen are
stimulated to proliferate by infection with HTLV-I. The chance of infection of such a cell
would be related to the infectious burden of virus.
Bystander damage hypothesis: In this hypothesis, HTLV-I infected CD4+ and anti-HTLV-I
specific CD8+ lymphocytes migrate across the blood–brain barrier, meet in the CNS and the
innocent glial cells are damaged by cytokines released against the infected lymphocyte.
Role of viral load for Pathogenesis: In cross sectional studies HTLV-I proviral load has been
found to be at least 10-fold higher in patients with HAM/TSP than in carriers. In patients
with TSP/HAM this viral burden was relatively constant over several months. In a
prospective study HTLV-I proviral load, whether high or low, remained relatively constant
over 2–3 years in most patients and carriers.
Epidemiology: With an estimated 20 million people infected worldwide, HAM/TSP is
Endemic in parts of Japan, South America, Africa, and the Caribbean, Iranian Jews.
Asymptomatic in majority of individuals with approximately 1-5% of HTLV-I carriers
developing disease 20-30yrs post infection. With a long clinical latency and low percentage
of individuals who develop disease suggest that T-cell transformation occurs after a series of
cellular alterations and mutations.
At Risk Groups:
•
Intravenous drug abusers.
•
Immigrants from high-risk areas.
•
Often associated with co-infection with HIV.
•
Endemic in certain parts of the southeastern US (Native Amerindian population).
Presentation of 25 Iranian cases of HTLV1 Associated Myelopathy
(HAM) Loghman Hospital Tehran in 2000-2006
Descriptive Statistics
N
age
age at onset
YEARS TO Dx
Severity
Min
25
25
25
25
Max
20
23
1
1
65
60
20
4
Mean
46.24
38.32
7.30
3.20
Sex Distribution and rout of initial presenting features:
Female = 64% Male = 36%
LIMBS INVOLVMENT
sex of patient
male
QUADRIPARESIS
LOWER LIMBS
female
Clinical Characteristics of Patients in Iran:
Clinical Characteristics of Patients in Peru :
Imaging finding:
CORD MRI FINDINGS
BRAIN MRI FINDINGS
HIGH SIGNAL LESIONS
CORD ATROPHY
NORMAL MRI OF SPINAL
NORMAL MRI OF BRAIN
Electrophysiological finding:
Geographical Distribution of Disease (Province of Birthplace and Province of living):
What is the most common Transmission pattern in Iran?
•
Infected blood products?
•
Sexual Transmission?
•
Breast feeding from infected mother?
•
IV abusing?
•
What about HIV and Hepatitis B Transmission in Iran?
Route of Transmission:
•
All of our patients were breast-fed for >12 months.
•
Breast-feeding is probably the main route of HTLV-1 transmission?
•
Blood transfusion was the second route.
Prevalence of infection in blood donors:
•
Saudi Arabia: 3/47426 (0.006%).
•
South America: 68/123,233 (0.05%).
•
Argentina: 40/19,426 (0.21%).
•
France: The overall prevalence is 0.039 per thousand.
•
Taiwan: 2311/3,701,087 (0.058%).
•
Caribbean Basin, Central Africa, and South Japan: greater than 1%.
•
Iran?
Is screening for anti HTLV-I/II antibodies In Iran necessary and cost effective to prevent
transmission through blood transfusions? Blood donors are routinely screened for HTLV-I/II
in North America, several countries in Europe, Japan, Peru, and Taiwan. There are
communications from other areas of endemicity that report a 16% decrease in HAM cases
only 2 years after the implementation of blood donor screening.
Summary of treatment options: Patients with more advanced disease, and possibly fixed
deficits may not benefit from either anti-inflammatory or antiretroviral treatment. Although
azidothymidine appears to have efficacy invitro against HTLV-I, it has not been clinically
successful in the treatment of HAM. This may reflect the fact that neuronal injury in HAM
may result from immunological attack by virus-specific cytotoxic T cells, rather than as a
result of direct viral infection. Consistent with this model of pathogenesis is the suggestion
that treatment with immunomodulatory agents including corticosteroids and interferon-a
may be beneficial in HAM.
Conclusion:
•
HAM is not rare in Iran.
•
Ham is not restricted to certain provinces like khorasan.
•
HAM is common between young females.
•
We don’t know the prevalence of infection.
•
We don’t know the effectiveness of blood screening.
Recommendations: Screening, at least in high risk groups, could be considered in health
programs. Urinary complaints were very prominent in our patients, so urologists and
gynecologists must be alerted about HAM. According recent studies, all treatments are
effective in first months/years of disease, so we must diagnose it as soon as possible.