Masafumi Hirato

Gamma knife for glioma: Selection factors and survival

PURPOSE To determine factors associated with survival differences in patients treated with radiosurgery for glioma. METHODS AND MATERIALS We analyzed 189 patients treated with Gamma Knife radiosurgery for primary or recurrent glioma World Health Organization (WHO) Grades 1-4. RESULTS CONCLUSION The median minimum tumor dose was 16 Gy (8-30 Gy) and the median tumor volume was 5.9 cc (1.3-52 cc). Brachytherapy selection criteria were satisfied in 65% of patients. Median follow-up of all surviving patients was 65 weeks after radiosurgery. For primary glioblastoma patients, median survival from the date of pathologic diagnosis was 86 weeks if brachytherapy criteria were satisfied and 40 weeks if they were not (p = 0.01), indicating that selection factors strongly influence survival. Multivariate analysis showed that increased survival was associated with five variables: lower pathologic grade, younger age, increased Karnofsky performance status (KPS), smaller tumor volume, and unifocal tumor. Survival was not found to be significantly related to radiosurgical technical parameters (dose, number of isocenters, prescription isodose percent, inhomogeneity) or extent of preradiosurgery surgery. We developed a hazard ratio model that is independent of the technical details of radiosurgery and applied it to reported radiosurgery and brachytherapy series, demonstrating a significant correlation between survival and hazard ratio. CONCLUSIONS Survival after radiosurgery for glioma is strongly related to five selection variables. Much of the variation in survival reported in previous series can be attributed to differences in distributions of these variables. These variables should be considered in selecting patients for radiosurgery and in the design of future studies.

An unusual variant of ependymoma with extensive tumor cell vacuolization

Abstract We report a case of ependymoma with unusual vacuolar features arising in the left occipital lobe of a 2-year-old child. The tumor was composed of cells with single or multiple cytoplasmic vacuoles and clear cells. Some cells showed a signet ring-like configuration. Clear cells were compactly arranged and showed an oligodendroglioma-like appearance. In addition, there were cellular ependymoma-like areas including perivascular pseudorosettes. On immunohistochemistry, glial fibrillary acidic protein and vimentin were mainly detected in cytoplasmic processes, and epithelial membrane antigen (EMA) staining showed granular and small vesicular reactivity. Ultrastructural investigation demonstrated intercellular microrosettes with or without cilia and long zonula adherens-type junctions that are typical of ependymoma. Furthermore, many intracytoplasmic lumina (ICL) were observed. Some ICL had microvilli and some did not. The latter varied in size, and may have fused with each other to develop giant ICL which could correspond to the signet ring-like configuration. Small ICL without microvilli had an appearance similar to that of distended endoplasmic reticula. Serial semithin and ultrathin sections revealed that EMA-positive structures were consistent with ICL containing microvilli and intercellular microrosettes. To determine the presence of unusual vacuolated ependymoma, electron microscopical examination was required. However, light microscopy was useful for detecting EMA-positive microvesicular and granular structures.

Microrecording for the Study of Thalamic Organization, for Tumor Biopsy and Removal

Use of microrecording technique in stereotactic selective thalamotomy, and in stereotactic biopsy for deep-seated lesions and in tumor removal was briefly described. For selective thalamotomy, the microrecording gives ample information to delineate thalamic subnuclei. Thus, the ventrointermedius (Vim) nucleus is identified by high-amplitude background activity and large-spike discharge, some of which responds solely to contralateral natural stimuli of kinesthetic modality. A small coagulation including this thalamic Vim point resulted in permanent arrest of the various kinds of tremor. As the normal brain tissue, whether the gray or white matter, is electrically active, the microrecording is useful to delineate the brain tumor from its surroundings. Stereotactic diagnostic biopsy and removal of the brain tumor were facilitated by this adjuvant method.

Gamma Thalamotomy for Parkinsonian and Other Kinds of Tremor

On the basis of our experiences with selective ventralis intermedius thalamotomy with microrecording, certain cases of tremor with Parkinsons disease (PD, six cases), intentional tremor (one case) and essential tremor (one case) were treated by Gamma Knife. In all cases, 140-150 Gy were irradiated using 4-mm collimators. Three different strategies were used. (1) Gamma thalamotomy as the primary surgical treatment. (2) As a secondary treatment, irradiation of the symmetric point of the contralateral selective thalamotomy. (3) Extension of the previous thalamotomy. For the first three cases (all PD), a special plug pattern (100 plugs) was used, but was not employed for the later cases. No acute untoward effects were noted, and overall there appeared to be a reduction in tremor. The time course of tremor reduction varied from case to case, from about 5-6 months to 1 year.

Pathophysiology of central (thalamic) pain: combined change of sensory thalamus with cerebral cortex around central sulcus.

In 13 patients with central (thalamic) pain after stroke, CT, MRI, PET scan and intraoperative thalamic microrecordings were performed. Electrophysiological studies showed that irregular burst discharges were often encountered in the posterolateral thalamus. The more often the irregular burst discharges were encountered, the greater the decrease of sensory response in the posterolateral thalamus. Metabolic studies showed that regional cerebral glucose metabolism decreased in both the posterolateral thalamus and in the cortical postcentral area on the lesioned side in all cases. In the thalamic lesion cases in which many irregular burst discharges were found in the posterolateral thalamus, regional cerebral glucose metabolism and the relative value of glucose to oxygen metabolism increased in the cortical precentral area on the lesioned side. It was suggested that decreased activity with abnormal burst discharge in the posterolateral (sensory) thalamus associated with changes in cortical activity adjacent to the central sulcus might be related to the genesis of central (thalamic) pain. It is emphasized that cortical activity decreased in the postcentral area, but often increased in the precentral area.

A special role of the parvocellular red nucleus in lesion-induced spontaneous tremor in monkeys.

The neural mechanisms underlying spontaneous tremor were investigated in monkeys. Tremor-producing ventromedial tegmental (VMT) lesions involve at least three major neural elements. (1) Parvocellular division of the red nucleus (RNpc); (2) cerebellothalamic fibers passing through the red nucleus, and, (3) nigrostriatal fibers. These three elements were destroyed stereotaxically in areas remote from the VMT area separately and/or in various combinations, and correlation between the site of lesions and tremor was made. Lesion-induced tremor appeared only when the three elements were destroyed. A possible, particular role of the RNpc in the production of the spontaneous tremor is discussed.

Gamma Knife Radiosurgery for Acoustic Schwannoma: Effects of Low Radiation Dose and Functional Prognosis

The effects of relatively low dose Gamma Knife irradiation on acoustic schwannoma were evaluated in 29 patients followed over 2 years after treatment. The mean dose delivered to the tumor periphery was 12.1 Gy. Lowering of the magnetic resonance signal intensity in the tumor center appeared in 69% and signs of tumor shrinkage appeared in 59% of cases. The cyst in the tumor enlarged in 3 cases, and 2 cases developed hydrocephalus. The percentage of pure-tone hearing preservation was 82% at 3 months, 73% at 6 months, 68% at 12 months. 64% at 18 months and 59% at 24 months in 22 out of 29 cases. Relatively low dose Gamma Knife radiosurgery was effective in suppressing tumor growth, with preservation of hearing.

Tremor-Mediating Thalamic Zone Studied in Humans and in Monkeys

The thalamic zone mediating the rhythmic burst activity related to the contralateral tremor was studied by microelectrodes in clinical cases with tremor and in monkeys with experimental tremor. The rhythmic burst time-locked with the tremor was found in a restricted area of the ventrointermedius nucleus (Vim) in humans and also in VPLo nucleus in monkeys. In both cases, only the lateral and ventrocaudal part of each nucleus, which was defined as the kinesthetic zone, was involved. A possible tremor-mediating neural circuit is postulated.

The Possible Role of the Cerebral Cortex Adjacent to the Central Sulcus for the Genesis of Central (Thalamic) Pain—a Metabolic Study

In nine patients with central (thalamic) pain after stroke, X-CT, MRI, PET scan and intraoperative thalamic microrecordings were performed. The PET studies made use of Sokoloffs method with 18FDG and a steady-state method with C15O2-15O2. CT scan and MRI revealed definite thalamic damage (Th) in 3 cases, putaminal damage (Put) in 3 cases, combined damage (Th + Put) in one case, and cortical (parietal) damage in 2 cases. In patients with a subcortical lesion, the greater the severity of superficial pain, the higher was the relative value of regional cerebral glucose metabolism (rCMRGlu) as compared to oxygen metabolism (rCMRO2) in the cerebral cortex around the central sulcus on the damaged side. Also, in a case with combined (Th + Put) lesion, regional oxygen extraction ratio (rOEF) was increased in this area. Moreover, in another case, central pain disappeared after a small subcortical haemorrhage in the same structure. In all patients including those with a cortical lesion, rCMRGlu was decreased in the postero-lateral (sensory) thalamus on the invalued side. The possible role of the cerebral cortex around the central sulcus for the genesis of central pain is discussed.

Gamma Knife Thalamotomy for the Treatment of Functional Disorders

Gamma Knife thalamotomy was performed with a 4-mm collimator in 2 cases with thalamic pain following a stroke and in 1 case of Parkinsons disease with tremor. In both cases with pain the maximum dose of 130 Gy was focused at the mediocaudal region of the previous thalamic lesion. In the case with tremor in Parkinsons disease, the maximum dose was 150 Gy. Longer follow-up is now proceeding, but the short-term results are encouraging. Based on data obtained from selective thalamotomy with depth microrecording, Gamma Knife thalamotomy could be a safe and effective technique for the treatment of these functional disorders.