Rationale and design to assess the efficacy and safety of HT047 in patients with acute ischemic stroke: A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase II trial.

BACKGROUND: Though several neuroprotective agents have been evaluated as potential treatments for acute ischemic stroke, none have demonstrated a definitive treatment efficacy, which remains elusive. HT047 is an herbal extract of Scutellaria baicalensis and Pueraria lobata, both of which have been widely used to treat ischemic stroke in traditional Korean medicine. The aims of this trial are to investigate whether HT047 can improve neurologic status, particularly motor function, in acute ischemic stroke patients, and to determine the safety of HT047. METHODS: A multicenter, double-blind, randomized, placebo-controlled, 3-arm parallel group, phase II trial will be conducted in patients who have had an acute ischemic stroke within the past 14 days. The participating patients must have a Fugl-Meyer assessment (FMA) motor score ≤55, with arm or leg weakness, and Korean version of the National Institutes of Health Stroke scale (K-NIHSS) score of ≥4 and ≤15. Seventy-eight participants will be randomized in a 1:1:1 ratio and given high-dose HT047 (750 mg 3 times a day), low-dose HT047 (500 mg 3 times a day), or a placebo for 12 weeks. The primary endpoint is the change in FMA motor score between baseline and week 12. Secondary endpoints are as follows: the change in FMA motor score at weeks 4 and 8 from baseline; the change in FMA motor score at weeks 4, 8, and 12 from baseline according to the timing of treatment initiation (either within 1 week, or 1-2 weeks), or according to the presence of prognostic risk factors (hypertension, diabetes, dyslipidemia, etc); the change in K-NIHSS and Korean versions of the modified Rankin scale (K-mRS) and the modified Barthel index at weeks 4 and 12 from baseline; and the proportion of subjects at week 12 with a K-NIHSS score of 0 to 2, or with K-mRS scores of 0, ≤1, and ≤2. DISCUSSION: This study is a 1st-in-human trial of HT047 to explore the efficacy and safety in acute ischemic stroke patients. The results will provide the appropriate dosage and evidence of therapeutic benefit of HT047 for stroke recovery. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02828540) Registered July 11, 2016.

Parsing brain activity associated with acupuncture treatment in Parkinson's diseases.

Acupuncture, a common treatment modality within complementary and alternative medicine, has been widely used for Parkinson's disease (PD). Using functional magnetic resonance imaging (fMRI), we explored the neural mechanisms underlying the effect of specific and genuine acupuncture treatment on the motor function in patients with PD. Three fMRI scans were performed in random order in a block design, one for verum acupuncture (VA) treatment, another one for a covert placebo (CP), and the third one for an overt placebo (OP) at the motor function implicated acupoint GB34 on the left foot of 10 patients with PD. We calculated the contrast that subtracts the blood-oxygen-level dependent (BOLD) response for the acupuncture effect (VA vs. CP) and the placebo effect (CP vs. OP). We found a significant improvement in the motor function of the affected hand after acupuncture treatment. The putamen and the primary motor cortex were activated when patients with PD received the acupuncture treatment (VA vs. CP) and these activations correlated with individual enhanced motor function. Expectation towards acupuncture modality (CP vs. OP) elicited activation over the anterior cingulate gyrus, the superior frontal gyrus, and the superior temporal gyrus. These findings suggest that acupuncture treatment might facilitate improvement in the motor functioning of patients with PD via the basal ganglia-thalamocortical circuit.

Amnesic syndrome in a mammillothalamic tract infarction.

It is controversial whether isolated lesions of mammillothalamic tract (MTT) produce significant amnesia. Since the MTT is small and adjacent to several important structures for memory, amnesia associated with isolated MTT infarction has been rarely reported. We report a patient who developed amnesia following an infarction of the left MTT that spared adjacent memory-related structures including the anterior thalamic nucleus. The patient s memory deficit was characterized by a severe anterograde encoding deficit and retrograde amnesia with a temporal gradient. In contrast, he did not show either frontal executive dysfunction or personality change that is frequently recognized in the anterior or medial thalamic lesion. We postulate that an amnesic syndrome can develop following discrete lesions of the MTT.