Takashi Tsuboi, Janine Lemos Melo Lobo Jofili Lopes, Kathryn Moore, Bhavana Patel, Joseph Legacy, Adrianna M. Ratajska, Dawn Bowers, Robert S. Eisinger, Leonardo Almeida, Kelly D. Foote, Michael S. Okun and Adolfo Ramirez-Zamora
Few studies have reported long-term outcomes of globus pallidus internus (GPi) deep brain stimulation (DBS) in Parkinson’s disease (PD). The authors aimed to investigate long-term outcomes of bilateral GPi DBS for 5 years and beyond for PD patients.
The authors retrospectively analyzed the clinical outcomes in 65 PD patients treated with bilateral GPi DBS at a single center. The outcome measures of motor symptoms and health-related quality of life (HRQoL) included the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Parkinson’s Disease Questionnaire (PDQ-39). Scores at baseline were compared with those at 1, 3, 5, and 6–8 years after implantation using Wilcoxon signed-rank tests with α correction.
GPi DBS significantly improved the off-medication UPDRS III total scores, UPDRS IV, and dyskinesia score at 1 year when compared with baseline (all p < 0.001). The off- and on-medication tremor scores, UPDRS IV, and dyskinesia scores showed moderate and sustained improvement (the ranges of the mean percentage improvement at each time point were 61%–75%, 30%–80%, 29%–40%, and 40%–65%, respectively) despite lacking statistical significance at long-term follow-up with diminishing sample sizes. The off-medication UPDRS III total scores did not show significant improvement at 5 years or later, primarily because of worsening in rigidity, akinesia, speech, gait, and postural stability scores. The on-medication UPDRS III total scores also worsened over time, with a significant worsening at 6–8 years when compared with baseline (p = 0.008). The HRQoL analyses based on the PDQ-39 revealed significant improvement in the activities of daily living and discomfort domains at 1 year (p = 0.003 and 0.006, respectively); however, all the domains showed gradual worsening at the later time points without reaching statistical significance. At 3 years, the communication domain showed significant worsening compared with baseline scores (p = 0.002).
GPi DBS in PD patients in this single-center cohort was associated with sustained long-term benefits in the off- and on-medication tremor score and motor complications. HRQoL and the cardinal motor symptoms other than tremor may worsen gradually in the long term. When counseling patients, it is important to recognize that benefits in tremor and dyskinesia are expected to be most persistent following bilateral GPi DBS implantation.
Takashi Morishita, Yoshio Tsuboi, Masa-aki Higuchi and Tooru Inoue
Nakao Ota, Rokuya Tanikawa, Hirotake Eda, Takashi Matsumoto, Takanori Miyazaki, Hidetoshi Matsukawa, Takeshi Yanagisawa, Go Suzuki, Shiro Miyata, Jumpei Oda, Kosumo Noda, Toshiyuki Tsuboi, Rihei Takeda, Hiroyasu Kamiyama and Sadahisa Tokuda
Bilateral vertebral artery dissecting aneurysms (VADAs) have a poor prognosis because progressive enlargement of the aneurysms compresses the brainstem or causes subarachnoid hemorrhage. The trapping of 1 vertebral artery (VA) places increased hemodynamic stress on the contralateral VA and may lead to enlargement and rupture. Therefore, management strategies are controversial. This study describes a radical treatment for bilateral VADAs using bypass surgery.
Seven patients with bilateral VADAs were included. Three patients were treated by trapping of 1 VA via coiling or clipping at another hospital; the previously treated VA in 1 patient and the contralateral untreated VA in 2 patients subsequently enlarged. The other 4 patients presented without previous intervention and progressive enlargement of the aneurysms.
The post–coil embolization patients underwent V3–posterior cerebral artery (PCA) bypass and trapping. The other 4 patients underwent VA reconstruction via V3–V4 or V4–V4 bypass, with contralateral trapping on a separate day in 3 patients and observation in 1 patient. Perioperative complications included 1 case of cerebrospinal fluid leakage for which the patient required an additional operation, 1 case of dysphagia and facial palsy due to sigmoid sinus thrombosis, and 1 case of dysphagia. The long-term outcomes of these patients were favorable.
Patients with bilateral VADAs require treatment on both sides. If VA trapping is performed first, the treatment options for the other side are limited to V3-PCA bypass and trapping. This procedure is effective; however, it is also invasive and technically difficult. In cases of bilateral VADAs in which it is feasible to reconstruct 1 side, the best approach is to begin by reconstructing the VA that appears technically easiest, followed by trapping of the contralateral VADA. This strategy allows enough time to suture vessels because contralateral reverse flow is maintained.
Eiichi Ishikawa, Yoshihiro Muragaki, Tetsuya Yamamoto, Takashi Maruyama, Koji Tsuboi, Soko Ikuta, Koichi Hashimoto, Youji Uemae, Takeshi Ishihara, Masahide Matsuda, Masao Matsutani, Katsuyuki Karasawa, Yoichi Nakazato, Tatsuya Abe, Tadao Ohno and Akira Matsumura
Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM.
Twenty-four patients (age 16–75 years, Karnofsky Performance Scale score ≥ 60% before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ. After a 4-week interval, the patients received 3 AFTV injections and the first course of TMZ maintenance chemotherapy for 5 days, followed by multiple courses of TMZ for 5 days in each 28-day cycle.
This treatment regimen was well tolerated by all patients. The percentage of patients with progression-free survival (PFS) ≥ 24 months was 33%. The median PFS, median overall survival (OS), and the actuarial 2- and 3-year survival rates of the 24 patients were 8.2 months, 22.2 months, 47%, and 38%, respectively. The median PFS in patients with a delayed-type hypersensitivity (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger surpassed the median length of follow-up for progression-free patients (29.5 months), which was significantly greater than the median PFS in patients with a smaller DTH-2 response.
The treatment regimen was well tolerated and resulted in favorable PFS and OS for newly diagnosed GBM patients. Clinical trial registration no.: UMIN000001426 (UMIN clinical trials registry, Japan).
Yoshihiro Muragaki, Takashi Maruyama, Hiroshi Iseki, Masahiko Tanaka, Chie Shinohara, Kintomo Takakura, Koji Tsuboi, Tetsuya Yamamoto, Akira Matsumura, Masao Matsutani, Katsuyuki Karasawa, Katsunori Shimada, Naohito Yamaguchi, Yoichi Nakazato, Keiki Sato, Youji Uemae, Tadao Ohno, Yoshikazu Okada and Tomokatsu Hori
The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme.
Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done—one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment.
The median duration of overall survival was 19.8 months (95% CI 13.8–31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3–13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection.
The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.