Optimal Treatment Decision for Brain Metastases of Unknown Primary Origin: The Role and Timing of Radiosurgery

BACKGROUND: Up to 15% of all patients with brain metastases have no clearly detected primary site despite intensive evaluation, and this incidence has decreased with the use of improved imaging technology. Radiosurgery has been evaluated as one of the treatment modality for patients with limited brain metastases. In this study, we evaluated the effectiveness of radiosurgery for brain metastases from unknown primary tumors. METHODS: We retrospectively evaluated 540 patients who underwent gamma knife radiosurgery (GKRS) for brain metastases radiologically diagnosed between August 1992 and September 2007 in our institution. First, the brain metastases were grouped into metachronous, synchronous, and precocious presentations according to the timing of diagnosis of the brain metastases. Then, synchronous and precocious brain metastases were further grouped into 1) unknown primary; 2) delayed known primary; and 3) synchronous metastases according to the timing of diagnosis of the primary origin. We analyzed the survival time and time to new brain metastasis in each group. RESULTS: Of the 540 patients, 29 (5.4%) presented precocious or synchronous metastases (34 GKRS procedures for 174 lesions). The primary tumor was not found even after intensive and repeated systemic evaluation in 10 patients (unknown primary, 34.5%); found after 8 months in 3 patients (delayed known primary, 1.2%); and diagnosed at the same time as the brain metastases in 16 patients (synchronous metastasis, 55.2%). No statistically significant differences in survival time and time to new brain metastasis were found among the three groups. CONCLUSION: Identification of a primary tumor before GKRS did not affect the patient outcomes. If other possible differential diagnoses were completely excluded, early GKRS can be an effective treatment option for brain metastases from unknown primary tumor.

Long-Term Results of Gamma Knife Radiosurgery for Intracranial Meningioma

BACKGROUND: The predominant treatment modality for meningioma is surgical resection. However, gamma knife radiosurgery is also an important treatment modality for meningioma that is small or cannot be completely removed because of its location. In this study, we evaluated the effectiveness and long-term results of radiosurgical treatment for meningioma in our institution. METHODS: We studied 628 patients (130 men and 498 women) who underwent gamma knife radiosurgery for intracranial meningioma, which is radiologically diagnosed, from Jan 2008 to Nov 2012. We included patients with single lesion meningioma, and followed up after 6 months with imaging, and then at 24 months with a clinical examination. Patients with high-grade meningioma or multiple meningiomas were excluded. We analyzed each of the factors associated with progression free survival. The median patient's age was 56.8 years. Maximal dosage was 27.8 Gy and marginal dosage was 13.9 Gy. RESULTS: The overall tumor control rate was 95%. Twenty-eight patients (4.4%) showed evidence of tumor recurrence. Ninety-eight patients (15%) developed peritumoral edema (PTE) after gamma-knife surgery; two of them (2%) underwent surgical resections due to PTE. Nine patients had craniotomy and tumor removal after gamma knife surgery. CONCLUSION: Gamma knife surgery for intracranial meningioma has proven to be a safe and effective treatment tool with successful long-term outcomes. Gamma knife radiosurgery can be especially effective in cases of remnant meningioma after surgical resection or where PTE is not present.

Temporal Hollowing Augmentation with Titanium Mesh after Autologous Cranioplasty in Temporal Muscle Resected Case: A Case Report / 대한신경손상학회지

Temporal fossa hollowing can represent a serious cosmetic concern to patients after post-traumatic surgery, oncological resection, or surgical dissection for obtaining access to the temporal area. Various methods have been described to augment temporal fossa hollowing, such as use of autogenous bone and cartilage implants, high-density polyethylene implants, and dermal fat grafts. We report a case of 22-year-old man with temporal fossa hollowing after post-traumatic surgery, including temporal muscle resection, whose defect was augmented by using titanium mesh even though long after cranioplasty.

Temporal Hollowing Augmentation with Titanium Mesh after Autologous Cranioplasty in Temporal Muscle Resected Case: A Case Report / 대한신경손상학회지

Temporal fossa hollowing can represent a serious cosmetic concern to patients after post-traumatic surgery, oncological resection, or surgical dissection for obtaining access to the temporal area. Various methods have been described to augment temporal fossa hollowing, such as use of autogenous bone and cartilage implants, high-density polyethylene implants, and dermal fat grafts. We report a case of 22-year-old man with temporal fossa hollowing after post-traumatic surgery, including temporal muscle resection, whose defect was augmented by using titanium mesh even though long after cranioplasty.

Gamma Knife Radiosurgery for Remnant or Recurred Craniopharyngiomas

OBJECTIVE: The authors assess the long term effectiveness of gamma knife radiosurgery(GKS) for remnant or recurred craniopharyngiomas on tumor control and possibly set proper radiation dose for tumor control with utmost preservation of the adjacent structures. METHODS: Sixteen GKS were done in 14 patients with recurred or remnant craniopharyngiomas after surgery. Mean follow up duration was 44.2 months (range 11.3~123.6 months). Follow up MR imagings were analyzed. RESULTS: Mean tumor volume was 3.6 cm3 (range 0.6~18 cm3) and mean margin dose was 12.2Gy (range 8~22.4Gy). Tumor control was achieved in 87.5% (14 of 16 tumors) which were either solid or cystic in nature. Dose to optic apparatus was mean 7.9Gy and no radiation related complications were observed. CONCLUSION: GKS seems to be effective treatment modality for craniopharyngiomas regardless of nature of tumor whether it is cystic or solid. Dose of 8 to 8.5Gy may be sufficient to achieve long term tumor control for remnant or recurred craniopharyngiomas.

The Role of Gamma Knife Radiosurgery for Diffuse Astrocytomas

OBJECTIVE: The management of diffuse astrocytomas is one of the most controversial areas in clinical neurooncology. There are numerous reviews and editorials outlining the difficulties in the management of these lesions. In this study, we assess the role of Gamma Knife radiosurgery(GKS) for diffuse astrocytomas. METHODS: Twenty-three patients with a diffuse astrocytoma were treated with GKS as a primary or adjuvant method from February 1995 to October 2003. The mean marginal dose was 13.6 (8.5~17.5)Gy and the mean maximal dose was 27.3 (17.0~35.0)Gy. Local control and the pattern of radiologic response were evaluated. The probable factors affecting local control, such as tumor volume, margin dose, previous history of craniotomy or stereotactic biopsy, and the presence or absence of previous radiotherapy were statistically analyzed. The average duration of follow-up was 39.7 (11.3~101.5) months after GKS. RESULTS: Of the 23 lesions treated, 16 lesions (69.6%) were controlled during the follow-up period. The mean progressionfree interval was 57.4 months and the 5-year progression-free rate was 68%. Only tumor volume was found to be a statistically significant factor for local control. Smaller tumors were better controlled by GKS; it was significantly effective in tumors with less than a 10 cm3 volume. CONCLUSION: GKS could be a valuable therapeutic modality both as a primary treatment and as a postoperative adjuvant therapy in some selected cases.

Bilateral anterior cingulotomy for refractory obsessive-compulsive disorder: Long-term follow-up results / 中国神经精神疾病杂志

Background Cingulotomy is alternative lesion treatment to anterior capsulotomy for severe obsessive-compulsive disorder (OCD) which is proved to be beneficial to alleviate the recurrent obsessive thoughts and uncontrollable, compulsive reactions. To investigate the long term efficacy and adverse cognitive effects of stereotactic bilateral anterior cingulotomy as a treatment for refractory obsessive compulsive disorder (OCD) patients,seventeen patients suffering from refractory OCD underwent stereotactic bilateral anterior cingulotomies and were followed for 24 months.Methods The Yale-Brown Obsessive-Compulsive Scale (YBOCS), the Clinical Global Impression (CGI), and other neuropsychological tests were used to assess the efficacy and cognitive changes of cingulotomy.Tests were taken before surgery and 12 and 24 months after surgery.Results The mean improvement rate of the YBOCS score achieved from the baseline was 48%. Eight patients out of 17 met responder criteria. During the 24-month follow-up, there were no significant adverse effects observed after surgery.Conclusions Bilateral anterior cingulotomy for the treatment of refractory OCD was effective, and no other significant adverse cognitive effects on long-term follow-up were found.

Effects of Hydroxychloroquine Co-administered with Chemotherapeutic Agents on Malignant Glioma Cell Lines: in vitro Study

OBJECTIVE: Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. METHODS: Two malignant glioma cell lines (U87MG, T98G) were treated with chemotherapeutic agents alone or with anti-malaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-(4, 5-dimethyl-2-thiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay following optimization of experimental conditions for each cell lines and cell viability was calculated. RESULTS: In all of four chemotherapeutic agents(doxorubicin, vincrisitne, nimustine, and cisplatin), the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance(ANOVA) yielded a statistically significant two-sided p-value of 0.0033(doxorubicin), 0.0005(vincrisitne), 0.0007(nimustine), and 0.0003(cisplatin) on U87MG cell lines and 0.0006(doxorubicin), 0.0421(vincrisitne), 0.0317(nimustine), and 0.0001(cisplatin) on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. CONCLUSION: Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.

Therapeutic Effects of Holmium-166 Chitosan Complex in Rat Brain Tumor Model

This study examined the effectiveness of Holmium-166 (Ho-166) chitosan complex therapy for a malignant glioma. Cultured C6 glioma cells (100, 000 in 5microliter) were injected into the caudate/putamen of 200 - 250 gram Wistar rats. Five days later, a Ho-166 chitosan complex was injected into the same site of the glioma injection. Four injection doses were administered: the control group received PBS 10microliter, group 1 received an injection of 100micro Ci (10microliter), group 2 received an injection of 50microCi (5microliter), and group 3 received an injection of 10micro Ci (1microliter). The average tumor volume for each group was 1.385 mm3 for the control group, 0.036 mm3 for group 1, 0.104 mm3 for group 2, and 0.111 mm3 for group 3. Compared with the control group, the size of the tumors in groups 1, 2 and 3 was reduced by an average of 97.4%, 92.5% and 91.9%, respectively. The Kaplan-Meier survival curve of group 2 was the longest, followed by groups 3, group 1 and the control. The mean survival was 22.8, 59, 60, and 44.6 days for the control group and groups 3, 2 and 1, respectively. H-E staining revealed that group 2 yielded the best results in the destruction of the malignant glioma. TUNEL staining and immunohistochemical studies indicated apoptotic features. The Ho-166 chitosan complex proved to be effective in destroying the malignant glioma.

Treatment Strategy of Multiple Hemangioblastomas

OBJECTIVE: Hemangioblastomas are highly vascular and benign neoplasm of the central nervous system(CNS). They can often be found as multiple lesions, as is commonly observed in von Hippel-Lindau(VHL) disease. The aim of this study is to determine the proper management for multiple hemangioblastomas. METHODS: Since 1990, 78cases of hemangioblastoma have been encountered. Among these, 9cases were multiple hemangioblastomas that were treated with surgical resection with or without radiosurgery. The medical, radiological, surgical and histological records were reviewed retrospectively and analyzed statistically. RESULTS: Nine patients presented with multiple hemangioblastomas and were diagnosed as VHL disease. The mean follow-up duration was 75.7months (6.6~159.2months) after the first surgical treatment. Three patients were treated with surgical resection alone and six patients were treated by both surgical resection and radiosurgery. Twenty-one surgical procedures (13 surgical resections and 8 radiosurgery) were performed. One patient required ventriculoperitoneal shunt and a posterior fossa decompressive craniectomy because of post-radiation brain swelling. Another patient refused additional treatment for the newly developed lesions after the successful treatment of initial lesions. The other patient who presented with numerous lesions in the whole brain and spine underwent cranio-spinal irradiation. Remaining patients showed good results. CONCLUSION: The surgical outcomes for the patients with a single lesion of the CNS hemangioblastoma are favorable. However, the treatment of multiple hemangioblastoma is more difficult, and should be treated by surgical resection and radiosurgery with careful consideration.

Pineal Cavernous Malformations: Report of Two Cases

Pineal hemorrhage only occurs in rare cases, and this known to have several different causes such as germ cell tumors, pineal cysts and vascular malformations, including the cavernous malformations. Pineal cavernous malformations are extremely rare: to date only fifteen cases have been reported worldwide. Although the diagnosis of pineal cavernous malformation is not easy because of the extreme rareness of this condition, the presence of this lesion can be suspected based on its typical radiological findings. Case 1. A 42-year- old man presented with a limitation in his upward gazing. Radiologic examinations showed acute hemorrhage in the pineal region. He underwent ventriculo-peritoneal (VP) shunting but the patient's condition deteriorated after the shunting surgery. We operated and totally removed the tumor and the hemorrhages via an occipital-transtentorial approach. Case 2. A 37-year-old man presented with diplopia. Radiologic examinations showed acute hemorrhage in the third ventricle. He underwent VP shunting, and after this procedure the diplopia was aggravated. We operated and totally removed the tumor and the hemorrhages via an occipital-transtentorial approach. If there is no doubt about the pineal cavernous malformation on MR imaging, we strongly recommend early surgical intervention without performing a risky biopsy. In this study, we describe our experiences for the diagnosis of cavernous malformations in the pineal region with special emphasis on the radiological aspects and the clinical course of this disease.

Effects of Methylprednisolone on the Neural Conduction of the Motor Evoked Potentials in Spinal Cord Injured Rats

Methylprednisolone (MP), a glucocorticoid steroid, has an anti-inflammatory action and seems to inhibit the formation of oxygen free radicals produced during lipid peroxidation in a spinal cord injury (SCI). However, the effects of MP on the functional recovery after a SCI is controversial. The present study was conducted to determine the effects of MP on the recovery of neural conduction following a SCI. A SCI was produced using the NYU spinal cord impactor. A behavioral test was conducted to measure neurological disorders, and motor evoked potentials (MEPs) were recorded. According to the behavioral test, using BBB locomotor scaling, MP-treated animals showed improved functional recoveries when compared to salinetreated animals. MEP latencies in the MP-treated group were shortened when compared to those in the control group. Peak amplitudes of MEPs were larger in the MP-treated group than those in the control group. The thresholds of MEPs tended to be lower in the MP-treated group than those in the control group. These results suggest that MP may improve functional recovery after a SCI.

Surgical Treatment of Cavernous Malformation of Pineal Region

The main causes of pineal apoplexy are hemorrhage associated with pineal region tumors, vascular malformations, and pineal cysts. Cavernous malformations rarely occur in the pineal region, with only fifteen cases reported previously. Hemorrhage associated with cavernous malformation causes apoplectic event in the pineal region. We report two surgically treated cases of pineal hemorrhage associated with cavernous malformation and discuss the consideration in management of the pineal apoplexy.

Surgical Treatment of Cavernous Malformation of Pineal Region

The main causes of pineal apoplexy are hemorrhage associated with pineal region tumors, vascular malformations, and pineal cysts. Cavernous malformations rarely occur in the pineal region, with only fifteen cases reported previously. Hemorrhage associated with cavernous malformation causes apoplectic event in the pineal region. We report two surgically treated cases of pineal hemorrhage associated with cavernous malformation and discuss the consideration in management of the pineal apoplexy.

Comparison of Thalamotomy with Deep Brain Stimulation in Essential Tremor

OBJECTIVE: Thalamic lesioning and deep brain stimulation(DBS) have proved to be beneficial to the treatment of essential tremor(ET). The authors compared the effects and complications of two modalities. METHODS: A total of 34 patients with ET were treated with ventral intermediate(Vim) nucleus thalamotomy or Vim DBS from May 1999 to May 2003. The procedure of lesioning or stimulation were performed as usual manner with or without microelectrode recording. Postoperatively, utilizing the various combinations of frequency, voltage and pulse width optimized the stimulation. The degree of improvements of tremor and the occurrence of the complications were evaluated postoperatively and at follow-up. RESULTS: There were 38 procedures, including 27 with Vim thalamotomy and 11 with DBS, in 34 patients. Of the thalamotomy group, left Vim lesioning is 25 and right one is 2. Follow-up duration ranged from 12 to 57 months. In the thalamotomy group, the rate of overall good outcome was 88.9% but 12 patients (44.4%) showed permanent adverse effects. In the cases of stimulation, the rate of overall good outcome was 90.9% and two patients had acceptable dysarthria. CONCLUSION: Both Vim thalamotomy and Vim DBS were effective for the treatment of ET, although perioperative adverse effects tended to be higher in patients who had thalamotomy. In cases of DBS, adjustments of stimulation parameters enabled an acceptable position to be achieved with tremor control and unwanted effects.

The Course of Brainstem Cavernous Malformations according to Management Strategies / 대한뇌혈관외과학회지

The outcome and the rate of rebleeding of brainstem cavernous malformationss were analyzed following conservative treatment, microsurgical excision and Gamma Knife radiosurgery (GKS). We especially concentrated on the role of radiosurgery. We treated 39 patients with brainstem cavernous malformations using conservative treatment, microsurgical removal or GKS from April 1993 to November 2003. Follow up duration was 7 to 132 months (mean 45.8, median 30.6). The lesion location included pons, midbrain, medulla oblongata and cerebellarpeduncle. Conservative management was performed in 14 patients, GKS in 18 patients and microsurgical removal in 7 patients. The annual rate of rebleeding was 22.2% in conservative group and 22.7% in GKS group. Good and moderate outcome were obtained in 70% of conservative group, 75% of GKS group and 85.6% of surgical group. Overall mortality rate was 5.1%. Microsurgical excision tended to be resulted in good outcome. GKS and conservative managements were accompanied by a risk of recurrent bleeding, even death. There was no statistical difference in outcome and the rate of rebleeding between conservatively managed group and GKS treated group.

Alterations of Spontaneous Behaviors and the Neuronal Activities of the Deep Cerebral Nuclei by Subthalamic Lesion with Kainic Acid in Rat Parkinsonian Models with 6-hydroxydopamine

OBJECTIVE: The purpose of this study is to investigate the effect of ipsilateral subthalamic nucleus(STN) lesioning on the spontaneous behavioral changes and the alteration of neuronal activities of deep cerebral nuclei in the rat parkinsonian model with 6-hydroxydopamine(6-OHDA). METHODS: To identify the spontaneous behavioral changes, apomorphine-induced rotational test and forepaw adjusting step were performed. We subsequently investigated the alteration of neuronal activities in the substantia nigra pars reticulata(SNpr) and globus pallidus(GP), in order to compare them with the behavioral changes in rat parkinsonian models. RESULTS: The STN lesioning in the rat parkinsonian model clearly improved behavioral changes. Compared to the normal control rats, rat PD models exhibited a significant increase in mean firing rates and the percentage of bursting neurons in the STN and SNpr. In the STN-lesioned rat PD models, mean firing rates and the percentage of bursting neurons in the SNpr were reduced and those in the GP increased. CONCLUSION: STN lesioning induced behavior improvement in rat parkinsonian models seems to be consistent with the surgical outcomes of the STN stimulation therapy in advanced Parkinsonn's disease(PD). The alteration of the neuronal activities in the SNpr and GP suggests that these sites are responsible for the improvement of parkinsonian motor symptoms observed following STN lesioning in rat parkinsonian models. The significance of bursting activity in the SNpr and GP remains obscure. Further study is necessary to elucidate the pathophysiological mechanism of PD.

Thoracoscopic Limited T3 Sympathicotomy for Primary Hyperhidrosis: Prevention for Compensatory Hyperhidrosis

OBJECTIVE: This study evaluates the role of thoracoscopic T3 sympathicotomy for the treatment of primary hyperhidrosis and the prevention of compensatory hyperhidrosis. METHODS: Thoracoscopic T3 sympathicotomy was performed on 27 patients with either isolated palmar hyperhidrosis (n=24) or in combination with axillary hyperhidrosis (n=3), from February 1999 to February 2002. In the case of combined palmar and axillary hyperhidrosis, additional coagulation of T4 sympathetic ganglion was performed. The mean follow-up period was 26.7 months. Operative results were determined on the basis of complications, compensatory hyperhidrosis, and patient satisfaction. RESULTS: The immediate postoperative results showed that all 24 patients with palmar hyperhidrosis reported complete alleviation of their symptoms. One patient with palmar and axillary hyperhidrosis for whom the axillary hyperhidrosis was not completely resolved underwent a second T4 sympathicotomy one month after first operation. There were two patients who suffered mild compensatory hyperhidrosis(7.4%). All 27 patients reported a high long-term satisfactory rate (average score; 7.93/10). One patient required a chest tube for treating pneumothorax. Other complications such as Horners syndrome, intercostal neuralgia, gustatory hyperhidrosis, and pulmonary edema were not observed. CONCLUSION: Thoracoscopic limited T3 sympathicotomy is an effective method to treat primary hyperhidrosis with a low rate of compensatory hyperhidrosis and a high rate of long-term satisfaction.

Treatment of Callosal Arteriovenous Malformations

OBJECTIVE: To establish management strategy and to improve outcome of callosal arteriovenous malformations(AVMs), forty-six consecutive cases hospitalized from 1984 to 2001 are analyzed. METHODS: Clinical and radiologic files were reviewed. Average follow-up period was 20.3 months in microsurgery group, and 28.2 months in radiosurgery group. RESULTS: The resection rate of microsurgery was considered total in 12 patients(85.7% ), subtotal 2(14.3%). The final clinical outcome of microsurgery was good in 13 patients(92.8%), fair in 1(7.2%). One patient with splenial lesion had postoperative disconnection syndrome. Initial insults and hemodynamic complications were the major cause of an unfavorable outcome. In radiosurgery the complete regression of nidus was considered in 16 patients(51.6%), partial shrinkage in 13(41.9%), and no response in 2(6.5%). The clinical outcome of radiosurgery was good in 26 patients(83.9%), fair in 3(9.75%), and poor in 2(6.5%). Rebleeding during the latency period(3 patients), radiation necrosis(1 patients) and initial insults(1 patients) were the major cause of postradiosurgery morbidity. Rebleeding during the latency period occurred in 3 patients(9.7%). Two lesions were in the splenium, and one lesion in the body of corpus callosum. All lesions were larger than 3cm in diameter. Two of them occurred during the second year, and the rest one during the third year of latency period. CONCLUSION: Microsurgery, which eliminates the risk of bleeding immediately, is referred for callosal AVMs. Radiosurgery is another effective treatment modality for splenial lesions with large bridging veins that interfere with microsurgical approach, and combined endovascular treatment would be strongly recommended for the splenial lesions larger than 3cm in diameter that has higher risk of hemorrhage during the latency period.

Radiological and Hormonal Responses of Functioning Pituitary Adenomas after Gamma Knife Radiosurgery

In this study, we examined patients with functioning pituitary adenoma that underwent Gamma Knife radiosurgery (GKS). In particular, we assessed the effects of GKS on the growth and endocrinological response of the functioning pituitary adenoma. Forty-two cases of functioning pituitary adenoma treated with GKS were analyzed. The mean follow-up duration was 42.5 months (range 6 - 98), and the mean tumor volume was 1.4 cm3 (range 0.1 - 3.8). Multiple isocenters, ranging from 1 to 6 in number (mean 2.7), were used. The tumor margin was covered by an isodose ranging from 50 to 90%. The margin dose was 18 to 40 Gy (mean 28.5) and the maximum dose varied from 35 to 80 Gy (mean 54.1). Tumor growth was controlled in 96.9% of the cases and tumor shrinkage occurred in 40.6% of the cases. Hormonal response was observed in 35 of the 42 (83.3%) patients after GKS, with a mean duration of 6.8 months. Sixteen of the 42 (38.1%) patients showed hormonal normalization, with a mean duration of 21 months. In our multivariate analysis, high integral dosage (p=0.005) and maximum dosage (p=0.001) correlated significantly with hormonal normalization. For patients with functioning pituitary adenoma, GKS can be effective in controlling tumor growth and inducing hormonal normalization, especially if patients are reluctant to undergo surgical resection, or are not able to undergo microsurgery under general anesthesia. It appears that early hormonal normalization can be induced by high maximum dosage (at least 50 Gy) and broad coverage of the target volume within the isodose curve, while keeping the maximum dose to the visual pathways below 9 Gy.