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  • Author or Editor: Tomohiko Mizutani x
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Yoichi Katayama, Masahiko Kasai, Hideki Oshima, Chikashi Fukaya, Takamitsu Yamamoto, Katsuhiko Ogawa and Tomohiko Mizutani

Object. A blinded evaluation of the effects of subthalamic nucleus (STN) stimulation was performed in levodopaintolerant patients with Parkinson disease (PD). These patients (Group I, seven patients) were moderately or severely disabled (Hoehn and Yahr Stages III–V during the off period), but were receiving only a small dose of medication (levodopa-equivalent dose [LED] 0–400 mg/day) because they suffered unbearable side effects. The results were analyzed in comparison with those obtained in patients with advanced PD (Group II, seven patients) who were severely disabled (Hoehn and Yahr Stages IV and V during the off period), but were treated with a large dose of medication (500–990 mg/day).

Methods. The patients were evaluated twice at 6 to 8 months after surgery. To determine the actual benefits afforded by STN stimulation to their overall daily activities, the patients were maintained on their medication regimen with optimal doses and schedules. Stimulation was turned off overnight for at least 12 hours. It was turned on in the morning (or remained turned off), and each patient's best and worst scores on the Unified Parkinson's Disease Rating Scale during waking daytime activity were recorded as on- and off-period scores, respectively. The order of assessment with respect to whether stimulation was occurring was determined randomly.

The STN stimulation markedly improved daily activity and total motor scores in Group I patients. The percentage time of immobility (Hoehn and Yahr Stages IV and V) became 0% in patients who were intermittently immobile while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, akinesia, and gait subscores. The STN stimulation produced less marked but still noticeable improvements in the daily activity and total motor scores in Group II patients. The percentage time of immobility as well as the LED was reduced in patients who displayed intermittent immobility with pronounced motor fluctuations while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, and dyskinesia subscores in these patients. In contrast, STN stimulation did not improve the overall daily activities at all in patients who had become unresponsive to a tolerable dose of levodopa and were continuously immobile, even though these patients' tremor and rigidity subscores were still improved by stimulation.

Conclusions. Consistent with earlier findings, the great benefit of STN stimulation in levodopa-intolerant patients is that STN stimulation can reduce the level of required levodopa medication. This suggests that STN stimulation could be a therapeutic option for patients with less-advanced PD by allowing levodopa medication to be maintained at as low a dose as possible, and to prevent adverse reactions to the continued use of large-dose levodopa.

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Tomohiko Mizutani, Herbert I. Goldberg, Justin Parr, Clive Harper and Carson J. Thompson

✓ A 19-year-old white man developed aphasia and right hemiplegia after several falls while waterskiing. Cerebral angiography displayed a ripple appearance and a “string of beads” sign along the left middle cerebral artery, with occlusion or stenosis of most of its branches. The patient died after 6 days, of transtentorial herniation due to massive left cerebral infarction. At necropsy, the infarct was found to be due to a subintimal dissecting aneurysm of the left middle cerebral artery. Multifocal areas of intimal fibroelastic thickening (IFT) were found not only at the site of dissection, but also in the other cerebral arteries, most prominent at the bifurcations of the vessels.

A systematic study of cerebral arteries performed in six control cases revealed that IFT was present in a similar distribution to that seen in the patient described. However, the degree of IFT in this patient was greater than in the controls. Some individuals with excessive IFT may be more susceptible to cerebral dissecting aneurysm under a variety of stresses, especially trauma.

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Tomokazu Aoki, Tomohiko Mizutani, Kuniharu Nojima, Takehisa Takagi, Ryosuke Okumura, Yoshiaki Yuba, Tetsuya Ueba, Jun A. Takahashi, Shin-Ichi Miyatake, Kazuhiko Nozaki, Waro Taki and Masao Matsutani

Object

The prognosis of recurrent glioblastoma multiforme (GBM) remains unsatisfactory. The authors conducted a Phase II study of ifosfamide, carboplatin, and etoposide (ICE) for a first recurrence of GBM to determine whether it prolonged a patient's good-quality life.

Methods

This trial was an open-label, single-center Phase II study. Forty-two patients with a first GBM relapse after surgery followed by standard radiotherapy (60 Gy) and first-line temozolomide- or nimustine-based chemotherapy were eligible to participate. The primary end point was progression-free survival at 6 months after the ICE treatment (PFS-6), and secondary end points were response rate, toxicity, and overall survival. Chemotherapy consisted of ifosfamide (1000 mg/m2 on Days 1, 2, and 3), carboplatin (110 mg/m2 on Day 1), etoposide (100 mg/m2 on Days 1, 2, and 3), every 6 weeks.

Results

Progression-free survival at 6 months after ICE treatment was 35% (95% CI 22–50%). The median duration of PFS was 17 weeks (95% CI 10–24 weeks). The response rate was 25% (95% CI 9–34%). Adverse events were generally mild and consisted mainly of alopecia.

Conclusions

This regimen was well tolerated and has some activity and could be one of the options for patients with recurrent GBM.