Focused Ultrasound Thalamotomy for Refractory Essential Tremor: A Japanese Multicenter Single-Arm Study.

BACKGROUND: Several feasibility studies and a randomized, controlled, multicenter trial have demonstrated the safety and efficacy of unilateral transcranial magnetic resonance-guided focused ultrasound (FUS) lesioning of the ventral intermediate thalamic nucleus in treating essential tremor. OBJECTIVE: To evaluate the safety and efficacy of FUS thalamotomy in a Japanese patient cohort through a prospective, multicenter, single-arm confirmatory trial. METHODS: A total of 35 patients with disabling refractory essential tremor underwent unilateral FUS thalamotomy and were followed up for 12 post-treatment months. Safety was measured as the incidence and severity of treatment-related adverse events. Efficacy was measured as the tremor severity and quality of life improvements using the Clinical Rating Scale for Tremor and Questionnaire for Essential Tremor. RESULTS: The mean skull density ratio (SDR) was 0.47. There was a significant decrease in the mean postural tremor score of the treated hand from baseline to 12 mo by 56.4% (95% CI: 46.7%-66.1%; P < .001), which was maintained at last follow-up. Quality of life improved by 46.3% (mean overall Questionnaire for Essential Tremor score of 17.4 [95% CI: 12.1-22.7]) and there were no severe adverse events. The most frequent adverse event was gait disturbance and all events resolved. CONCLUSION: Unilateral FUS thalamotomy allowed significant and sustained tremor relief and improved the quality of life with an outstanding safety profile. The observed safety and efficacy of FUS thalamotomy were comparable to those reported in a previous multicenter study with a low SDR, and inclusion of the low SDR group did not affect effectiveness.

Effects of Anserine/Carnosine Supplementation on Mild Cognitive Impairment with APOE4.

BACKGROUND: Oral supplementation of anserine/carnosine helps preserve cognitive functions in healthy older adults. Mild cognitive impairment (MCI) is a transition between cognitive-normal and dementia. Therefore, it needs to investigate whether anserine/carnosine supplementation (ACS) has effects on subjects with MCI. METHODS: A randomized, double-blind, placebo-controlled 12-week trial was performed. Fifty-four subjects with MCI were randomized to an active group ingesting 750 mg of anserine and 250 mg of carnosine per day or a placebo (1:1). Evaluation of cognitive change was conducted utilizing a psychometric test battery. RESULTS: The score improvement in the global Clinical Dementia Rating (gloCDR) was superior in the active group than placebo (p = 0.023). No beneficial effect in the active group was detected in the other psychometric tests including the Mini-Mental State Examination (MMSE), the Wechsler Memory Scale, and the Alzheimer's Disease Assessment Scale (ADAS). When APOE4 positive (APOE4 (+)) or negative (APOE4 (-)) subjects were separately analyzed, beneficial change in the APOE4 (+) subjects was observed in MMSE (p = 0.025) as well as in gloCDR (p = 0.026). CONCLUSIONS: The present study might suggest that protective effects against cognitive decline in APOE4 (+) MCI subjects exist.

A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up.

OBJECTIVE: Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. METHODS: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. RESULTS: Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years. INTERPRETATION: Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice.

Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies.

Effects of essence of chicken on cognitive brain function: a near-infrared spectroscopy study.

The aim of this study was to investigate the effects of the essence of chicken on brain function by near-infrared spectroscopy. Twelve healthy elderly subjects took the essence of chicken or a placebo for 7 d in a double-blind cross-over design study. Changes in oxy-hemoglobin concentrations in the bilateral prefrontal areas of the brain were measured while the subjects performed the simple reaction task, the Groton Maze Learning Test, and the working memory task. In the latter case, there were significant interactions in the changes in oxy-hemoglobin concentrations between treatment and period of intake according to two-way repeated ANOVA. The changes in oxy-hemoglobin concentrations significantly increased in several regions of the prefrontal areas of the brain in those taking essence of chicken for 7 d. These results suggest that essence of chicken is useful as a nutritional supplement to enhance or maintain brain function in the elderly.

Bilberry extract protect restraint stress-induced liver damage through attenuating mitochondrial dysfunction.

The aim of the present study is to investigate the protective effect of bilberry extract on liver damage in restraint stressed mice. A remarkable increase in alanine aminotransferase (ALT) and reactive oxygen species (ROS) levels was observed in stressed mice. Treatment with bilberry extract restored ALT and ROS to normal levels, and enhanced mitochondrial complex II activity that was lowered in restraint stressed mice. The mitochondrial electron transfer chain (ETC)-related gene expression was measured by RT-PCR, and a significant up-regulation of complex II mRNA was observed for SDHA, B, C and D mRNA in bilberry extract-treated group compared with that in stressed group. Bilberry extract administration also profoundly elevated the Na(+)-K(+)-ATPase activity and mitochondria membrane potential (∆Ψ(m)), which was reduced in the stressed group. Bilberry extract exhibited protective effect by scavenging free radicals and attenuating mitochondrial dysfunction in the liver of restraint stressed mice. It may be used as a promising therapeutic agent in preventing and delaying the life-related disease.

Assamicin I and II, novel triterpenoid saponins with insulin-like activity from Aesculus assamica Griff.

Two novel triterpenoid saponins with insulin-like activity, termed assamicin I and II, were isolated from the roots of Aesculus assamica Griff. and their structures were characterized as 1 and 2, respectively. They inhibited release of free fatty acids from epinephrine-treated rat adipocytes and enhanced glucose uptake into 3T3-L1 adipocytes.