It is known that the motor functions of patients with FCMD peak from 2 to 8 years of age and start regressing at around 4–8 years of age. Once regression starts, it is understood that the motor functions never recover . In the present study, we administered a steroid orally to nine patients with FCMD whose motor functions had started regressing and observed improvements in all of them. This result suggests that steroid therapy may help these patients improve or maintain their motor functions after they have already started regressing. While previous case studies focused on patients with mild FCMD, including cases that gained the ability to walk [13, 14], we administered steroid therapy not only to mild cases, but also to typical and severe types. Consequently, we observed improved motor functions in patients of all clinical types. In the mild and typical types, the patients gained the ability to perform actions that were previously impossible (Table 2). In the severe cases, the patients were able to stabilize the previously unsteady neck and trunk and sit unaided, showing an improvement in the peak motor ability (Table 2).
The initial steroid dose was 0.5 mg/kg on an alternate-day basis, and, for the non-responders, the dose was increased up to 1.0 mg/kg on an alternate-day basis. Regarding the correlation between the steroid dose and its effects, no statistical analysis could be performed because of the small sample size. Nevertheless, even when the alternate-day administration regimen at 0.5 mg/kg was ineffective, increasing the steroid dose tended to improve the motor functions, thereby suggesting that therapeutic effects are felt at high doses rather than at low doses. Moreover, according to reports by Toyono et al., alternate-day administration at 0.5 mg/kg (0.25 mg/kg/day) had a definite effect. As opposed to the minimum dose (prednisone at 0.3 mg/kg/day) demonstrated to be effective against DMD, even lower doses may contribute to improving the motor functions of the patients with FCMD [9, 10, 13].
In addition to improving motor functions, the previously reported effects of steroid therapy include improvement in swallowing functions, intensification of voice volume, and improvement in the peak expiratory flow rate [13–15]. In the present study, two cases achieved a decrease in salivation, and one case witnessed an intensified voice volume (Table 2). Although decreased salivation suggests improvement in swallowing functions, an intensified voice volume may be related to improvement in vital capacity. Similar to steroid therapy for DMD, steroid therapy for FCMD may also contribute to the improvement of swallowing and pulmonary functions. Moreover, six cases exhibited improved motivation, and two cases attained increased vocabulary, indicating that the central nervous system was also affected, in addition to motor functions (Table 2). Patients with FCMD exhibit dysphagia prior to a decrease in the respiratory functions. Therefore, to prevent aspiration and asphyxiation, they sometimes require gastric fistula formation or tracheoesophageal separation . Improvement in the swallowing functions by steroid therapy will lead to a better quality of life among patients with FCMD.
Regarding the start/finish times of steroid therapy, our study focused on the patients whose motor functions started regressing. Toyono et al. administered steroid therapy to patients who were capable of walking and whose motor functions reached a developmental plateau, and reported that their walking and moving speed increased . In our study, we administered steroid therapy to patients with severe-type FCMD whose motor functions had started regressing; consequently, the patients became able to sit unaided and attained improved peak motor performance. This finding suggests that starting steroid therapy before the motor functions reach a developmental plateau and start regressing may improve the peak motor performance. However, in FCMD, the timing of the establishment of a developmental plateau of motor functions differs greatly from patient to patient. In severe-type FCMD, patients reach a plateau at around 2 years of age. Hence, steroid therapy should be initiated from an earlier age. In such cases, several issues should be considered, such as preventing adverse reactions, including growth suppression, and inoculating live vaccines.
Regarding the end time of steroid therapy, the consequences of its long-term administration, in addition to the functional improvement, should be considered, as in steroid therapy for DMD. Once the therapy is found to no longer improve motor functions, it is essential to factor in the risk–benefit balance and decide whether to continue the therapy in consultation with the patients and their guardians. The repercussions of long-term steroid administration also need to be assessed in the future.
The limitations of this study was small sample size, and included the different steroid doses administered to the patients and the rather long time that was needed to confirm the drug compliance. All patients refused to take prednisolone orally because of its bitter taste. Because patients with FCMD have moderate-to-severe mental retardation, their parents often encounter this type of problem during the administration of the medication. The adverse reactions to steroid therapy occurred during the short period of this study were not sufficiently severe to justify the discontinuation of the therapy; however, one patient could not receive an increased dose because of the anxiety of the parents regarding the irritability of the patient. Hence, we believe that steroid therapy can be administered safely. In future studies, we need to assess the effects of the long-term administration of these drugs, especially when therapy is initiated at an early age.
As mentioned above, for steroid therapy in FCMD, there are still points of consideration, including the dosage and start/finish times. Nonetheless, the results of this study suggest that steroid therapy is effective in improving/maintaining the motor functions of patients with FCMD for a short period. The fact that steroid therapy improves and maintains the motor functions of patients signifies that it could also improve their quality of life.