Familial Clusters of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

Abstract

ObjectiveHTLV-1 proviral loads (PVLs) and some genetic factors are reported to be associated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, there are very few reports on HAM/TSP having family history. We aimed to define the clinical features and laboratory indications associated with HAM/TSP having family history.MethodsRecords of 784 HAM/TSP patients who were hospitalized in Kagoshima University Hospital and related hospitals from 1987 to 2012 were reviewed. Using an unmatched case-control design, 40 patients of HAM/TSP having family history (f-HAM/TSP) were compared with 124 patients suffering from sporadic HAM/TSP, who were admitted in series over the last 10 years for associated clinical features.ResultsOf the 784 patients, 40 (5.1%) were f-HAM/TSP cases. Compared with sporadic cases, the age of onset was earlier (41.3 vs. 51.6 years, p<0.001), motor disability grades were lower (4.0 vs. 4.9, p = 0.043) despite longer duration of illness (14.3 vs. 10.2 years, p = 0.026), time elapsed between onset and wheelchair use in daily life was longer (18.3 vs. 10.0 years, p = 0.025), cases with rapid disease progression were fewer (10.0% vs. 28.2%, p = 0.019), and protein levels in cerebrospinal fluid (CSF) were significantly lower in f-HAM/TSP cases (29.9 vs. 42.5 mg, p<0.001). There was no difference in HTLV-1 PVLs, anti-HTLV-1 antibody titers in serum and CSF, or cell number and neopterin levels in CSF. Furthermore, HTLV-1 PVLs were lower in cases with rapid disease progression than in those with slow progression in both f-HAM/TSP and sporadic cases.ConclusionsWe demonstrated that HAM/TSP aggregates in the family, with a younger age of onset and a slow rate of progression in f-HAM/TSP cases compared with sporadic cases. These data also suggested that factors other than HTLV-1 PVLs contribute to the disease course of HAM/TSP.

Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4

“…Similarly to ATLL, the main risk factor for developing HAM is a high proviral load of HTLV-1, but there are others factors, like some gene polymorphisms, such as polymorphisms of IL28B [102] that imply a genetic predisposition to this condition. This family aggregation and its particular characteristics have been described recently by Nozuma et al [103]. Remarkably in a recent cohort study up to 30% of asymptomatic carriers presented mild neurological symptoms not fulfilling HAM/TSP criteria (sensory, motor, autonomic or urinary symptoms) [104].…”

Family Aggregation of Human T-Lymphotropic Virus 1-Associated Diseases: A Systematic Review

“…The HAM/TSP cases with a family history of HAM/TSP had a slower rate of HAM/TSP progression and an earlier age of onset (mean 41.3 years) than sporadic cases (mean 51.6 years). There was no difference in HTLV-1 proviral load between the two groups (Nozuma et al, 2014). Four other records mention an early age of onset of HAM/TSP in some relatives of HAM/TSP patients (Miyai et al, 1987; McKhann et al, 1989; Kayembe et al, 1990; Cartier et al, 1998), but only Nozuma et al evaluated this in a systematic way (Nozuma et al, 2014).…”

“…Thirteen of them were designed to identify or explain family aggregation, including 10 cross-sectional studies (Kondo et al, 1985; Matsuo et al, 1989; Kayembe et al, 1990; Tajima, 1990; Bhigjee et al, 1995; Iwanaga et al, 1995; Pombo-de-Oliveira et al, 2001; Cabada et al, 2007; Alvarez et al, 2014; Nozuma et al, 2014), two reviews (Manns and Qasba, 1999; Shoeibi et al, 2013), and one cohort study (Iwanaga et al, 2010). The remaining 61 records were either case reports or reports of family clusters that were identified within other epidemiological studies.…”

Neurological manifestations in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis in the Amazon

“…This disease has no cure yet, only palliative treatment to minimize the clinical symptoms. 1,13 The individuals with HTLV-1 treated at the Epidemiological Clinic of Endemic Diseases of the Tropical Medicine Sector of the Federal 14 who employed these criteria to screen patients, and in studies conducted by Starling et al 15 and Costa et al 16 . In the present investigation, as in the aforementioned studies, the patients were screened using the criteria proposed by De Castro-Costa.…”