Limitations
SECONDARY
Our study had some limitations. First, the researchers were not blinded to the treatment allocation due to practical reasons concerning the sham condition, what could have introduced bias during the treatment period. In addition, although we performed double-blinded assessment of the primary outcome at 3 months, most secondary outcomes were assessed in a single-blind fashion. However, the considerably shorter length of stay in the rehabilitation center strongly suggests that the benefits observed on the other secondary outcomes are real.Second, the sham condition did not consist of electrical stimulation to mask sensory sensations on the scalp evoked by peripheral nerve stimulation during TMS, and successful blinding of patients was not verified by asking patients which treatment group they believed they were assigned to. However, all patients were naive to cTBS treatment, which potentially reduces the bias introduced by limitations in the sham condition.Third, we only measured the duration of upper limb therapy that patients received during the 2-week treatment period and the week thereafter. However, it is unlikely that patients in both groups received different durations of upper limb therapy after this period, as all patients were part of the same treatment schedule. While upper limb therapy content was balanced between groups at onset of treatment, this may have changed based on the additional improvement in upper limb function due to active cTBS, in accordance with the CARAS protocol. However, because both patients and therapists were blinded to treatment allocation, we consider it unlikely that patients in the active cTBS group received different upper limb therapy content unless the change in therapy was the direct result of improved motor function caused by active cTBS.Fourth, we only scored the upper limb component of the FMA. Assessment of the lower limb component could have provided insights into the specificity of the treatment.Fifth, the investigated sample consisted predominantly of males, which could limit generalizability of the results to females.Finally, our treatment paradigm was based on the theoretical interhemispheric imbalance model. However, we did not explicitly evaluate the interhemispheric balance before or after the intervention.