Evidence of FNRIP efficacy has been reported by various studies (Côté et al., 2018). Such findings indicate that multidisciplinary protocols can enable neural reorganization associated with synaptogenesis, and support the introduction of locomotor training as a primary rehabilitation modality (Lavrov et al., 2006; Martins, 2015; Mehrholz et al., 2012, 2017). During the present study, 67 dogs regained functionality and 57 achieved an OFS of 13, with only conscious/sub-conscious proprioceptive deficits. Ten dogs achieved functional “spinal reflex” locomotion (OFS 0 – FSRL), contributing to an overall result of 79.8% (67/84) functionality.
The study population was characterized by a mean age of 4.15 years and a mean weight of 9.13 kg, similar to the characteristics reported by Aikawa et al. (2012), Gallucci et al. (2017), and Zidan et al. (2018). The most frequently noted breed was the French Bulldog, which was not consistent with the report of Ruddle et al. (2006) or Zidan et al. (2018), who reported the highest frequency in Dachshunds. The lesion site in the present study was similar to that of most other studies for anatomical reasons (Jeffery et al., 2016; Gallucci et al., 2017; Zidan et al., 2018).
Neurological progression was not observed between days 1 and 3, and dogs maintained either an OFS of 0 or 1. This indicated a pre-selected population of 51 dogs with an OFS of 1, with absent/decreased flexor peripheral reflexes (inclusion criteria) and dogs with an OFS of 0. All dogs were referred by veterinary neurologists, because of exuberant epidural haemorrhage with venous sinus involvement that could have compromised their functional recovery (Amsellem et al., 2003).
Twenty-nine dogs with an OFS of 0 showed no recovery of DPP until the fourth week. Two recovered on day 30 after FNRIP implementation (Fig. 4C) and the remaining four recovered following the administration of 4-aminopyridine (Fig. 4D). Therefore, 21% (6/29) recovered owing to the synaptic and anatomical neuroplasticity achieved by the possible combination of locomotor training, electrostimulation, and in some cases, 4-aminopyridine, which unlocked a possible lack of connection between the brain stem and spinal locomotor network silenced by inhibitory effects (Mehrholz et al., 2012, 2017).
In the present study, an overall functionality of 55% (16/29) was observed in dogs with an OFS of 0, 21% (6/29) of the dogs recovered DPP at a later time point (after day 30), and 35% (10/29) achieved FSRL, within a maximum of 3 months. Recovery of DPP after 30 days is reflective of the pre-selected population, and is suggestive of “complete” spinal cord injury, or unsuccessful neurological cases.
According to Jeffery et al. (2016), DPP recovery is subjective. Thus, it is essential to restrict the evaluation at each time point and, in order to decrease subjectivity, to ensure that it is assessed by the same assessor, at the same time of the day and in the same environment, as performed in the present study. Also, it is important to mention that the authors believe that in the cases of FSRL (10/29), and given the coordination in the locomotor pattern achieved, there was a possible evidence of residual descending pathways, in agreement with Lewis et al. (2018).
The results of the present study are time-limited. The FSRL was achieved within 2–3 months and all dogs were closely monitored at each time point (days 7, 15, 30, 45, 69, 75, and 90). In addition, the follow-ups over 6 months showed a sustained FSRL in 30% of the dogs observed over 2 years without locomotory differences. There are no other studies with such prolonged follow-ups, which proves that this type of locomotion is sustainable over time and can be achieved in 2–3 months with intensive neurorehabilitation protocols.
For Jeffery et al. (2016), this type of locomotion could be developed usually within many months, and for Aikawa et al. (2012) was achieved within approximately 9 months. For Olby et al. (2003), 38.8% could achieve this locomotion within a mean of 37.6 weeks.
Regarding dogs with an OFS of 1, reported success rates after surgical approach can range from 85–98% (Olby et al., 2003, 2004; Loughin et al., 2005; Ruddle et al., 2006; Aikawa et al., 2012; Draper et al., 2012; Ingram et al., 2013; Langerhuus & Miles, 2017). However, comparison between studies can be difficult given the definition of success. Most studies reported success as achieving ambulatory state, without considering proprioceptive ataxia (Hodgson et al., 2017). Contrary to other reports, in the present study 80% of dogs had medical discharge within 30 days of FNRIP implementation, but with an OFS of 13 and minimum neurological deficits
In the present study there was a total functionality of 79.8% (67/84). Complete recovery could be attributed to the application of bipedal/quadrupedal locomotor training. This form of training is a rehabilitative procedure that promotes repetitive and progressive practice of the flexion/extension locomotor pattern (Harkema et al., 2012; Escalona et al., 2017). It can activate afferent inputs Ia and Ib due to muscle spindle stretching. This may have a direct connection with the hip mechanoreceptor joint (Bouyer & Rossignol, 2003; Dietz & Muller, 2004; Pearson, 2008; Rossignol & Frigon, 2011) and can activate the spinal locomotor network and CPG, facilitating recovery of the flexion/extension locomotor pattern (Thompson et al., 2013; Thompson & Wolpaw, 2014a; Solopova et al., 2015). In addition, sensory cutaneous receptor stimulation can be achieved by contact pressure on the treadmill (land and underwater) (van de Crommert et al. 1998; Guertin 2014), allowing the regulation of swing and stance locomotion phases (Dietz, 2011).
One of the possible explanations lies in the association between locomotor training and FES that may have facilitated a possible conversion of type II fibers to type I (Côté et al., 2017). This is essential for postural support while standing (Postans et al., 2004). Depending on the cathode-anode orientation, it can also lead to the potential regeneration and activation of new connections (Thompson & Wolpaw, 2015).
In addition, the authors believe that TESCS could promote the stimulation of residual motor descending pathways, and therefore, the spinal locomotor network (Minassian et al., 2016; Hofstoetter et al., 2014, 2015).
The results obtained in the present study were neither age nor weight-dependent, which was inconsistent with most previous studies (Olby et al., 2003; Ruddle et al., 2006; Gallucci et al., 2017). Also, there was no possible comparation between this study and Zidan et al. (2018), given the differences among population groups, with 51 paraplegics with absent/decreased flexor reflex and 33 dogs with an OFS of 0, in contrast to 9 non-ambulatory paraparetic dogs and 6 paraplegic dogs from the other study.
Considering the functional outcome, this study found close results compared to those presented by Langerhuus & Miles (2017) ´ systematic review and meta-analysis, but they were completed within a time frame of 2–3 months.
No cases of self-mutilation were observed, as there was an absence of paraesthesia through the FNRIP that allowed neuromodulation (Smania et al., 2010). In contrast to the reports of other authors (Olby et al., 2003; Aikawa et al., 2012), no urinary tract infections were observed. This could be attributed to the full-time hospitalization regime with higher levels of supportive care, electrical stimulation protocols (Ladouceur & Barbeau, 2000; Sims et al., 2015), and greater anatomical neuroplasticity with neural reorganization (Wolpaw & Tenissen, 2001). Thus 79.3%, all OFS 0-FSRL and OFS 0-NSRL patients had medical release with autonomous miction.
There were several clinical study limitations. One was the experimental design without inter-observer and intra-observer examination. Nevertheless, images were reviewed by independent two observers (neurologist and CCRP). Additionally, no scale was applied to dogs without DPP. Although a specific scale exists, it could not have been included in the present study because it was not used consistently for all cases (Martins et al., 2018). Furthermore, it is important to note the need for future studies that would more accurately specify various scores that are applicable to dogs without DPP (OFS of 0), which could be related to their possible functionality.