# Portable RGB-D Camera-Based System for Assessing Gait Impairment Progression in ATTRv Amyloidosis
## 1 Introduction  
Hereditary Amyloidosis associated with variant Transthyretin (ATTRv Amyloidosis) is a rare, highly disabling, and inherently progressive neurologic disease. It is caused by an autosomal dominant genetic mutation in which Valine, located in position 30 of the TTR protein, is replaced by Methionine (V30M) [1]. The peripheral nervous system is especially affected by this disease, specifically the large myelinated as well as small non-myelinated fibers. This disorder is a nerve length-dependent symmetric polyneuropathy associated with autonomic dysfunction, which may lead to death within a decade from onset if left untreated [1; 2; 3]. In Portugal and Japan, the disease is usually reported as beginning in the third, fourth, or fifth decade of life; onset occurs typically later in patients from other geographical areas [4]. Its prevalence in northern Portugal (Povoa de Varzim and Vila do Conde) was estimated to be 176.01/100,000 adult inhabitants in 2016 [5], representing the largest worldwide cluster of individuals with this condition. In Portugal, cumulative disease risk in individuals with the V30M mutation is estimated to be 80% by the age of 50 and 91% by the age of 70, whereas the risk in French heterozygotes is 14% by the age of 50 and 50% bythe age of 70 [6]. In Sweden, the penetrance is lower at 11% by the age of 50 and 36% by the age of 70, only reaching 52% prevalence by the age of 80 [7]. ATTRv Amyloidosis typically begins with the loss of temperature and pain sensations and hyperesthesia of the feet, in a slow progression of sensorimotor and autonomic neuropathy [3,4]. Afterward, sensory disturbances spread from the foot soles to the insteps, ankles, lower legs, knees, and thighs in a length-dependent manner. With further progression, motor deficits develop in the feet and progress in a proximal direction as well as in a length-dependent manner. By the time sensory neuropathy progresses to the level of the knees, the hands usually also become affected. In the late stage of the disease, sensory loss, muscle atrophy, and weakness of the extremities show a glove and stocking distribution (the name usually given to the symptom distribution in the areas covered by gloves or stockings). Foot drop and disability of the hands and fingers are also common symptoms of motor neuropathy. The disease can be classified into the following three stages: (I)--sensory polneuropathy, (II)--progressive walking disability, and (III)--wheelchair-bound or bedridden [8]. Regarding treatment options, orthotopic liver transplantation was the first implemented approach (1990s) that succeeded in slowing disease progression [9,10]. In 2007, oral disease-modifying treatment became available for daily intake and has demonstrated long-term efficacy, although the deterioration of both clinical and neurophysiological domains was reported after 2 years of drug intake for some patients [11,12]. Other treatment options are under development [4,13,14]; however, challenges in clinical assessment remain due to the disease's rareness and a consequent lack of thorough knowledge, clinical heterogeneity, incomplete natural history, and uncertain treatment effectiveness [15]. Because treatment options in ATTRv amyloidosis are most beneficial at an early stage of the disease [4,10,16,17], the development and improvement of tools for objective measurements is of great importance [18]. ATTRv amyloidosis epidemiologic knowledge has expanded over the past years [19]. As in other neurologic diseases, motor polneuropathy in ATTRv amyloidosis is monitored using serial nerve conduction studies that measure how fast an electrical impulse moves through the nerves, to identify nerve damages. Yet, movement is still analyzed using mostly subjective methods--gait evaluation is solely based on observation and clinical interrogatory--despite these being perceived as insufficient by the clinical community and lacking precision for identifying early-stage or subtle changes [20,21].