Changes in the brain activation balance in motor-related areas after constraint-induced movement therapy; a longitudinal fMRI study.

PRIMARY OBJECTIVE: This study investigated the longitudinal changes in brain activation balance in motor-related areas after Constraint-Induced Movement Therapy (CIMT). METHODS AND PROCEDURES: The subjects included seven ischemic stroke patients with mild right hemiparesis. Eight normal subjects were also included. The patients underwent functional MRI and motor function tests (Fugl-Meyer Assessment; FMA, modified Wolf Motor Function Test; mWMFT) both before and immediately after CIMT and also after a 3-month follow-up. RESULTS: The motor function test scores improved immediately after CIMT; moreover, these scores were either maintained or improved even at the 3-month follow-up. In a comparison of the chronological data of the contralaterality index of the affected hand movement, the cerebellar activity changed significantly to ipsilateral activation immediately after CIMT and thereafter the cerebellar activity further changed to ipsilateral activation at the 3-month follow-up. A correlation was observed among the contralateral activation, FMA and mWMFT scores in SM1 and the ipsilateral activation and in the mWMFT scores in the cerebellum at the 3-month follow-up examinations. CONCLUSION: The participation of the contralateral SM1 and the ipsilateral cerebellum is thus considered to play an important role in the satisfactory recovery of the motor function after CIMT intervention.

Effect of modified constraint-induced movement therapy on lower extremity hemiplegia due to a higher-motor area lesion.

BACKGROUND: Modified CIT (mCIT) was performed in a stroke patient with a lesion in the left medial frontal region including the supplementary motor area (SMA), which is part of the higher-motor area, and whose primary symptom was motor ignition difficulty observed at the start of voluntary movement of the right leg. CASE STUDY: mCIT was performed from awakening to bedtime (not including bath time) with his non-affected limb fixed with a knee splint while he was in the hospital ward. Two days (the total time he wore the appliance was 19.5 hours) after the intervention was introduced, voluntary movement of the right leg occurred, and functional improvement was observed. CONCLUSIONS: These findings are speculated to be related to the facts that the unilateral SMA strongly contributes to movement of the ipsilateral limb and that the plasticity of the SMA, which is a higher-motor area, is greater than that of primary areas. It is probable that different regions of the brain have different plasticity, resulting in differences in the process of functional recovery and the level of recovery.

Inhibition of metastatic brain tumor growth by intramuscular administration of the endostatin gene.

The cancer patients suffering from brain metastases are basically incurable. The conventional tumoricidal strategies frequently cause severe side effects instead of life prolongation of such patients. On the other hand, antiangiogenic therapy seems to be a promising strategy to avoid such unfavorable effects. In the present study, we experimentally investigated tumor dormancy effect of the excessively produced endostatin, a potent angiostatic factor, by intramuscular administration of the endostatin gene against primary cancer and metastatic brain tumor. For this purpose, we established a model system in which FM3A P-15 cells, a high metastatic mouse breast cancer cell line, were inoculated simultaneously into the brain as an artificially metastatic brain tumor (herein referred as "metastatic brain tumor") and the mammary pad as a primary cancer (referred as "primary breast cancer"), and utilized a non-viral system to deliver an expression plasmid encoding a secretable form of mouse endostatin into muscle tissues. The plasmid vector formulated with the synthetic polymer, polyvinylpyrrolidone, was administrated at 3 and 10 days after the inoculation of FM3A P-15 cells. A significant increase in the serum level of endostatin was achieved at 7 days after second administration of the plasmid vector (p=0.0066). Consequently, the growth of metastatic brain tumor was significantly retarded (p=0.0455), while no significant change in the weight of primary breast cancer was observed (p=0.1531). Intratumoral microvessel density in metastatic brain tumor but not in primary cancer as revealed by Factor VIII immunohistochemistry was significantly decreased in the endostatin gene-administrated group (p=0.0027). In conclusion, the present study demonstrates the potential efficacy of intramuscular delivery of antiangiogenic gene for treatment of metastatic brain tumor.

Extraosseous accumulation of bone scanning agents in malignant brain tumors: comparison to semi-quantitative evaluation with 99mTc SPECT/201Tl SPECT and histological findings.

Although 201Tl chloride (Tl) SPECT has been used in the differential diagnosis between recurrence of malignant brain tumor and necrosis after treatment, it is not generally recognized as a definite modality to distinguish them. We conducted a preliminary study using Tl SPECT and 99mTc-MDP or 99mTc-HMDP (Tc) SPECT because it has been said that extraosseous accumulation was caused by calcium deposits in necrotic tissues. In our study, for the purposes of clarifying the mechanism of extraosseous uptake and the correlation between extraosseous accumulation of bone-scanning agent and tumor viability in malignant brain tumors, we compared whether Tc uptake was correlated with the histopathological findings and further performed semi-quantitative evaluation between Tc SPECT and Tl SPECT. The correlation coefficients between the ratio of tumor to normal skull count obtained from Tc SPECT (Tc-T/N) and those of tumor to normal brain count (T/N) and to normal scalp count (T/S) both obtained from Tl SPECT were calculated. Using contrast enhanced CT (CE-CT) or contrast enhanced MRI (CE-MRI), 8 of 10 cases showed intensely ring-enhanced tumor with necrotic lesion. Histopathologically, 7 of 8 cases whose tumor had been resected before treatment had necrosis with increased vascularity or bleeding. Of the remaining 2 cases one case, malignant lymphoma had only hypervascularity by biopsy, while the other one was excluded for resection after treatment. Three of these 8 cases whose CE-CT or CE-MRI showed necrotic lesions exhibited Tc and Tl accumulations in the area corresponding to necrosis. In contrast, 2 showed no Tc nor Tl uptake. Tc-T/N had no significant correlation with any of early-, delayed-T/N or T/S. In conclusion, there was no significant correlation between Tc and Tl uptakes by malignant brain tumors in semi-quantitative evaluation.

Extraosseous accumulation of 99mTc phosphonate complexes in primary brain tumor evaluated with SPECT.

Although extraosseous accumulations of 99mTc phosphate complexes are phenomena which can often be seen, no case showing extraosseous accumulation to brain tumor on SPECT has been reported. We report here two cases of primary brain tumor showing extraosseous accumulation of 99mTc phosphate in bone SPECT. 201Tl SPECT also showed increased 201Tl uptake by the tumor. Comparing bone SPECT with 201Tl SPECT, the regions of abnormality of both SPECTs were very similar in the case of glioblastoma, but in the case of malignant lymphoma the region showing intense uptake of 99mTc-MDP was smaller than that on 201Tl SPECT. It was revealed that bone SPECT is more useful in the assessment of extraosseous accumulation to a primary brain tumor than conventional bone scintigraphy.

Mirror observation of finger action enhances activity in anterior intraparietal sulcus: a functional magnetic resonance imaging study.

Mirror therapy can be used to promote recovery from paralysis in patients with post-stroke hemiplegia, There are a lot of reports that mirror-image observation of the unilateral moving hand enhanced the excitability of the primary motor area (M1) ipsilateral to the moving hand in healthy subjects. but the neural mechanisms underlying its therapeutic effects are currently unclear. To investigate this issue, we used functional magnetic resonance imaging to measure activity in brain regions related to visual information processing during mirror image movement observation. Thirteen healthy subjects performed a finger-thumb opposition task with the left and right hands separately, with or without access to mirror observation. In the mirror condition, one hand was reflected in a mirror placed above the abdomen in the MRI scanner. In the masked mirror condition, subjects performed the same task but with the mirror obscured. In both conditions, the other hand was held at rest behind the mirror. A between-task comparison (mirror versus masked mirror) revealed significant activation in the ipsilateral hemisphere in the anterior intraparietal sulcus (aIP) while performing all tasks, regardless of which hand was used. The right aIP was significantly activated while moving the right hand. In contrast, in the left aIP, a small number of voxels showed a tendency toward activation during both left and right hand movement. The enhancement of ipsilateral aIP activity by the mirror image observation of finger action suggests that bimodal aIP neurons can be activated by visual information. We propose that activation in the M1 ipsilateral to the moving hand can be induced by information passing through the ventral premotor area from the aIP.