Acupuncture for acute moderate thalamic hemorrhage: randomized controlled trial study protocol
In this randomized controlled trial, we will observe the effect of acupuncture therapy on patients with acute TH. The findings of this project are expected to provide evidence for the efficacy of acupuncture in improving the prognosis of patients with moderate TH. To minimize bias, stratified block randomization will be used according to sex and age, and the outcomes reviewer will be blinded. Subjects will be treated alone in a treatment room in order to avoid any communication with other subjects.
Generally speaking, no ideal placebo-controlled acupuncture trials have been performed previously [34]. Because recent acupuncture trials have examined so-called sham acupuncture techniques, including: needling of acupuncture points through non-penetrating needles, needling of non-acupuncture points, and needling of acupuncture points that are not indicated for that specific condition, these prior trials have not accurately reflected TCM theory and therefore have not properly assessed it [34]. Further complicating things is that sham acupuncture has been shown to have some efficacy [35]. In China, many patients and their families have had acupuncture at some time in their lives or are at least familiar with the acupuncture process. Therefore, it would be difficult to design a trial assessing the utility of sham acupuncture versus real acupuncture while keeping the patient blinded.
The decision was made to examine patients with left sided TH separately from patients with right sided TH. In the majority of patients, Broca’s cortical area and Wernicke’s cortical area are located in the left hemisphere. Therefore, patients with left hemisphere stroke (ischemic or hemorrhagic) are at risk for language deficits. Similarly, patients with right sided insults are at risk for symptoms of visual neglect. Both language deficits and visual neglect can have a profound impact on the way a patient responds to treatment and rehabilitation of other neurologic deficits. Therefore, to account for the potentially confounding effects of language deficits and visual neglect respectively, patients were subdivided into right and left TH subgroups.
Along the same lines, not all patients have their language centers located in their left hemisphere. While the majority of left handed patients have their language centers in the left hemisphere, some do have them in the right hemisphere. Therefore, in this study, we have only included right handed patients.
Another potentially confounding factor is the involvement of adjacent brain tissue as a secondary result of the initial thalamic insult. Adjacent brain tissue can necrose either directly via extension of the thalamic bleed or indirectly via mass effect from the thalamic bleed and/or edema related to the thalamic bleed. Areas at specifically high risk include the genu of the internal capsule which lies lateral to the thalamus, the posterior limb of the internal capsule which lies posterolateral to the thalamus, the anterior limb of the internal capsule which lies anterolateral to the thalamus, and the peri-thalamic/peri-ventricular white matter which lies superior to the thalamus. Involvement of the genu of the internal capsule, the posterior limb of the internal capsule, and adjacent white matter could result in paralysis. Involvement of the posterior limb of the internal capsule could also result in sensory loss or impaired comprehension [36]. Finally, involvement of the anterior limb of the internal capsule could result in cognitive issues. Involvement of any of these areas could potentially impact how a patient recovers and/or sway the post-stroke assessment scores in one direction or another depending on how many of the affected patients ended up in the control group or the intervention group. To combat this, we utilized two mechanisms. First, we excluded patients from the study whose TH on admission CT demonstrated extension of the insult beyond the thalamus. However, admission CT often does not disclose the true area affected by the insult. CT performed 90 days later is much more sensitive in demonstrating the insult’s true encompassment. We therefore further subdivided the groups by size. While all subjects in the study have moderate thalamic hemorrhage, groups were further subdivided into subjects with 10–15 cc of TH and 15–30 cc of TH. Patients with 10–15 cc of TH are much less likely to experience insults to brain tissue external to the thalamus than patients with 15–30 cc of TH as a result of the smaller size of the initial bleed. We also plan to retrospectively analyze the results of CT scans performed 90 days following the insult to determine what percent of patients in each group experienced extension of their primary insult to tissue beyond the thalamus and how this may have affected the results in that group. After dividing patients by side of hemorrhage and size of hemorrhage four intervention groups were established, and along with the corresponding four control groups, this totaled eight distinct subject groups.
Previous research has demonstrated that patients with hand paresis only following stroke may not only be the most likely to benefit from acupuncture therapy but also the most likely to experience complete resolution of their neurologic symptoms [37]. As a result, it is important, if able, to determine the results of our intervention in patients with hand paresis only. As only patients with moderate thalamic hemorrhage will be enrolled in this trial, it is unlikely that our study will include many, if any, subjects with hand paresis only. However, if there are subjects with hand paresis, the results of our intervention will be analyzed retrospectively following conclusion of the trial.
The primary outcome measure is NIHSS result. While the NIHSS is a fine test, its comprehensiveness is somewhat lacking. In fact, previous studies examining interventions in stroke patients may have failed due to their sole reliance on the NIHSS as an outcome measure [38]. Therefore, additional tests measuring paralysis, language, visual neglect, and stroke outcome were also included in this study.
Under strict quality control, this trial will attempt to answer the question of whether or not acupuncture can improve neurologic outcome following moderate TH.