The present study is the first longitudinal study of a complex and recessive form of spastic paraplegia prevalent in the semi-arid Northeast region of Brazil. Longitudinal studies are indicated to describe the progression rates in HSP and determine whether the nonlinear increase in disease severity in later disease stages reflects true disease evolution in HSP or represents an artefact of the cross-sectional study design [12]. To our knowledge, only two studies evaluated cross-sectional and longitudinal disease progression in HSP and most of the participants had the dominant forms[12], [13].
Our analysis allows asserting that Spoan individuals exhibited slight dependence until age 35. The greatest losses occurred from ages 35 to 41, and starting at 50, practically all patients become completely dependent. In fact, age is the main predictor factor of impaired motor function among Spoan syndrome patients. Among the 47 reassessed individuals, 14 had already lost their hand grip strength on the first assessment in 2007. Of the remaining individuals, 25 completely lost their hand grip strength over the following 10 years, and eight exhibited partial loss. All the participants needed to use a wheelchair, and only two were able to walk with some aid.
The loss of hand grip strength over the 10-year period was associated with higher levels of dependence. For the eight participants with preserved hand grip strength, the values obtained with the Jamar® dynamometer were less than half of the expected values. Unexpectedly, 21 of the participants with no hand grip strength were able to feed themselves somehow without any adaptation of the utensils.
The decline in the scores on the functional classification scale reflects the progressive nature of the disease with a marked axonal and sensory-motor neuropathy. Amorim et al. (2014) [14] conducted a study on nerve, motor and sensory conduction that involved 27 cases of people with Spoan syndrome aged between 4 and 58 years, of which 20 were women. All cases had severe neuropathic signs and demonstrated a deficit of force and distal atrophy, and 58% of them had deformities in the feet and spine. The deep reflexes of the upper limbs were exalted in 92% of the cases, and the patellar reflex in 63%; being the Aquileu reflex absent in all patients. No correlation was observed between age and conduction velocity, latency and amplitude of median and ulnar nerves. There was a reduction in conduction velocities in the median and ulnar nerves by 50 and 41%, respectively. The motor latencies of the axillary and femoral nerves were normal in all cases. Changes in driving speed are probably due to the loss of rapidly conducting nerve fibers 20 [14] .
Schüle and collaborators (2016) [12] evaluated 608 cases of HSPs and pointed out that the age of onset and disease duration showed the strongest effect on disease severity, whereby late age of onset and longer disease duration were associated with higher SPRS scores. In our cohort, the first symptoms, such as optic atrophy and spastic paraparesis, appear before age five and most frequently during the first year of life. In fact, it was not found a significant variation in the age at onset in Spoan syndrome. For this reason, no correlation was found between age at onset of symptoms and motor impairment or between motor impairment and sex, as described in follow-up studies of other rare genetic diseases [12],[13, 15, 16] .
Data from larger cohorts using measures validated for HSP are essentially missing in the literature [15]. In the present study, no significant difference was found on Schüle’s SPRS, Fink’s FHSPRS or the Ambulation Index revised by Chiaravalloti and DeLuca between 2007 and 2017. The participants’ ambulation was already highly impaired at the first assessment in 2007, as 70.21% of the sample spent more than 50% of their time in a wheelchair, and only three were able to walk. In 2017, 45 individuals (97.87%) had completely lost their ambulation ability and spent their entire days in a wheelchair. A high proportion of affected individuals had minimum or maximum scores on the scales, which might reduce variability of data and explain the outcomes.
Although the patients’ life expectancy was not investigated using suitable methods, it does not seem to decrease, since six participants were 60 years old or older, and one was 81 years old. Regarding causes of death, no repeated respiratory problems (pneumonia) were detected, as in other studies on rare genetic diseases [16],[17]. Therefore, Spoan syndrome is different from conditions such as Duchenne muscular dystrophy, in which the life expectancy is limited to two or three decades as a function of cardiac and respiratory involvement [18], and amyotrophic lateral sclerosis, with a life expectancy of two to five years after diagnosis [19], [20]. Some patients exhibited dysphagia, none required a feeding tube. The causes of death bore no relationship to the disease, and included cancer, infarction, stroke and congenital heart disease.
One of the limitations of the present study concerns the number and variety of the instruments applied at the time Spoan syndrome was first described, which restricted the number of predictive variables. For instance, psychological aspects of patients and their quality of life were not investigated on the earlier assessment. Moreover, it was not possible to establish whether rehabilitation and assistive technology might influence the speed of motor function impairment and the development of deformities, because seven individuals were only attending physiotherapy once a week. Residents of the state of Rio Grande do Norte still lack access to specialised rehabilitation services.