Impact of the number of metastatic brain lesions on survival after Gamma Knife radiosurgery.

Effectiveness of Gamma Knife radiosurgery (GKRS: Elekta AB, Stockholm, Sweden) for patients with metastatic brain disease and the prognostic factors influencing their survival were analyzed in a 5 year retrospective data analysis (July 2001 to June 2006). Kaplan-Meier survival curves were constructed using univariate and multivariate analyses with the respective salient prognostic factors. This study analyzed data on 330 patients with brain metastases who underwent GKRS. Lung carcinoma (55%) was the most common primary cancer followed by breast (17.8%), melanoma (9.4%), colorectal (4.8%) and renal (3.9%). The median survival for all patients was 8 months. Survival ranged from 13 months for breast metastases, 10 months for renal, and 8 months for lung to 5 months for colorectal and melanoma. Mean age of patients was 58.5 years (range 18-81). Melanoma patients were younger with a mean age of 49 and also had the highest number of lesions (3.8) when compared to patients with renal (2.5), lung (2.8), colorectal (3) and breast (3.6). When stratified according to the number of lesions patient survival was 8 months (one to three lesions), 7.5 months (four or five lesions) and 7 months (six lesions or more). Mean Karnofsky Performance Status score (KPS) was 77 and survival dropped significantly from 8 months to 4.5 months if KPS was less than 70. Survival improved with a KPS of 70 or more, regardless of the number of lesions treated. Selection of patients based on the number of lesions may not be justified. A prospective trial is required to further define the prognostic factors affecting survival.

Stereotactic radiosurgery in two cases of presumed fourth cranial nerve schwannoma.

A 47-year-old woman and a 45-year-old man with gradually progressive fourth cranial nerve palsy underwent stereotactic radiosurgery for presumed fourth cranial nerve schwannomas with the gamma knife at a marginal tumor dose of 14 and 13 Gy, respectively. In one patient, the ocular misalignment disappeared; in the other patient, it stabilized. MRI showed shrinkage of the tumors. These patients represent the second and third reported cases of presumed fourth cranial nerve schwannoma treated with radiosurgery and the first cases with substantial follow-up information.

Pharmacological modulation of cortical plasticity following kainic acid lesion in rat barrel cortex.

OBJECT: The brain shows remarkable capacity for plasticity in response to injury. To maximize the benefits of current neurological treatment and to minimize the impact of injury, the authors examined the ability of commonly administered drugs, dextroamphetamine (D-amphetamine) and phenytoin, to positively or negatively affect the functional recovery of the cerebral cortex following excitotoxic injury. METHODS: Previous work from the same laboratory has demonstrated reorganization of whisker functional responses (WFRs) in the rat barrel cortex after excitotoxic lesions were created with kainic acid (KA). In the present study, WFRs were mapped using intrinsic optical signal imaging before and 9 days after creation of the KA lesions. During the post-lesion survival period, animals were either treated with intraperitoneal D-amphetamine, phenytoin, or saline or received no treatment. Following the survival period, WFRs were again measured and compared with prelesion data. RESULTS: The findings suggest that KA lesions cause increases in WFR areas when compared with controls. Treatment with D-amphetamine further increased the WFR area (p < 0.05) while phenytoin-treated rats showed decreases in WFR areas. There was also a statistically significant difference (p < 0.05) between the D-amphetamine and phenytoin groups. CONCLUSIONS: These results show that 2 commonly used drugs, D-amphetamine and phenytoin, have opposite effects in the functional recovery/plasticity of injured cerebral cortex. The authors' findings emphasize the complex nature of the cortical response to injury and have implications for understanding the biology of the effects of different medications on eventual functional brain recovery.

Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma.

OBJECT: The purpose of this study was to examine the results of using Gamma Knife surgery (GKS) for brain metastases from classically radioresistant malignancies. METHODS: The authors retrospectively reviewed the records of 76 patients with melanoma (50 patients), renal cell carcinoma (RCC; 23 patients), or sarcoma (3 patients) who underwent GKS between August 1998 and July 2007. Overall patient survival, intracranial progression, and local progression of individual lesions were analyzed. RESULTS: The median age of the patients was 57 years (range 18-85 years) and median Karnofsky Performance Scale (KPS) score was 80 (range 20-100). Sixty-two patients (81.6%) had uncontrolled extracranial disease. A total of 303 intracranial lesions (average 3.97 per patient, range 1-27 lesions) were treated using GKS. More than 3 lesions were treated in 30 patients (39.5%). Median GKS tumor margin dose was 18 Gy (range 8-30 Gy). Thirty-seven patients (48.7%) underwent whole brain radiation therapy. The actuarial 12-month rate for freedom from local progression for individual lesions was 77.7% and was significantly higher for RCC compared with melanoma (93.6 vs 63.0%; p = 0.001). The percentage of coverage of the prescribed dose to target volume was the only treatment-related variable associated with local control: 12-month actuarial rate of freedom from local progression was 71.4% for lesions receiving >or= 90% coverage versus 0.0% for lesions receiving < 90% (p = 0.00048). Median overall survival was 5.1 months after GKS and 8.4 months after the discovery of brain metastases. Univariate analysis revealed that KPS score (p = 0.000004), recursive partitioning analysis class (p = 0.00043), and single metastases (p = 0.028), but not more than 3 metastases, to be prognostic factors of overall survival. The KPS score remained significant after multivariate analysis. Overall survival for patients with a KPS score >or= 70 was 7.1 months compared with 1.3 months for a KPS score 3 metastases. Higher rates of local tumor control were achieved for RCC in comparison with melanoma, and this may have an effect on survival in some patients. Although outcomes generally remained poor in this study population, these results suggest that GKS can be considered as a treatment option for many patients with radioresistant brain metastases, even if these patients have multiple lesions.

Functional barrel cortex in 'hairless', nude mice.

Although nude mice are not truly hairless, they demonstrate abnormal hair structure and growth patterns, which are related to their genetic state. Whereas wild-type mice are born with visible vibrissae, nude mice are distinguishable at birth by the lack of visible vibrissae, which do not appear until approximately postnatal day 6. Additionally, adult nude mice have abnormal whisker cycling patterns in which structurally normal whisker follicles produce fragile whiskers which break or fallout leaving follicles whiskerless for several days before a fine replacement whisker appears and develops. The current study shows that despite these abnormal periods of whisker deprivation, the barrel cortex of nude mice develops a normal structural appearance viewed with cytochrome oxidase staining. Additionally, intrinsic optical imaging studies of barrel cortex responses to single whisker stimulation do not appear altered from normal despite periodic loss of adjacent whiskers.

Ventral thoracic spinal cord herniation: frequently misdiagnosed entity.

STUDY DESIGN: Case report with review of the literature. OBJECTIVE: Symptomatic spinal cord herniation through ventral aspect of dura is frequently misdiagnosed because this condition is rare. The most frequent misdiagnosis was that of dorsal arachnoid cyst. The purpose of this article is to provide insight on clinical presentation, diagnosis, and surgical treatment of this entity. Results of our cases were compared with that of the reported literature. SUMMARY OF BACKGROUND DATA: Eighty-six cases reported in the literature were reviewed and data are presented in this article. METHODS: We had 3 patients diagnosed with spinal cord herniation through the ventral aspect of the dural sac. All 3 cases were misdiagnosed initially and later successfully operated. The dura was repaired primarily with suture in 1 case and with surgical graft in the other 2 cases. RESULTS: Reduction of spinal cord herniation reverses some of the signs and symptoms that have been present for years. Two of our patients had remarkable recovery in motor strength and bladder function. The third patient improved but remained with residual myelopathy. CONCLUSION: Ventral herniation of the thoracic spinal cord is a partially treatable cause of myelopathy, when recognized promptly and treated surgically. Recognizing this infrequent cause of myelopathy prevents misdiagnosis. Delay in diagnosis may impair recovery at a later date.

Gamma knife surgery for trigeminal neuralgia: improved initial response with two isocenters and increasing dose.

OBJECT: The authors sought to evaluate the initial response of trigeminal neuralgia (TN) to gamma knife surgery (GKS) based on the number of shots delivered and radiation dose. METHODS: Between September 1998 and September 2003, some 63 patients with TN refractory to medical or surgical management underwent GKS at Upstate Medical University. Ten patients had multiple sclerosis and 25 patients had undergone prior invasive treatment. Gamma knife surgery was delivered to the trigeminal nerve root entry zone in one shot in 27 patients or two shots in 36 patients. The radiation dose was escalated to less than or equal to 80 Gy in 20 patients, 85 Gy in 21 patients, and greater than or equal to 90 Gy in 22 patients. Pain before and after GKS was assessed using the Barrow Neurological Institute Pain Scale and the improvement score was analyzed as a function of dose grouping and number of shots. Sixty patients were available for evaluation, with an initial overall and complete response rate of 90% and 27%, respectively. There was a greater improvement score for patients who were treated with two shots compared with one shot, mean 2.83 compared with 1.72 (p < 0.001). There was an increased improvement in score at each dose escalation level: less than or equal to 80 Gy (p = 0.017), 85 Gy (p < 0.001), and greater than or equal to 90 Gy (p < 0.001). Linear regression analysis also indicated that there was a greater response with an increased dose (p = 0.021). Patients treated with two shots were more likely to receive a higher dose (p < 0.001). There were no severe complications. Five patients developed mild facial numbness. CONCLUSIONS: Gamma knife surgery is an effective therapy for TN. Initial response rates appear to correlate with the number of shots and dose.

Effects of hyperoxia on human sensorimotor cortex activity produced by electrical stimulation of the median nerve: a functional magnetic resonance imaging study.

This study investigated the effect of hyperoxia on sensorimotorcortical activity resulting from electrical stimulation of the median nerve, using functional magnetic resonance imaging (fMRI). Nine volunteers underwent stimulation at 5 and 100 Hz while breathing 21% FIO(2) (fraction of inspired oxygen) or 100% FIO(2). fMRI data were correlated with a stimulus predictor curve, transformed into Talairach space and averaged by group. Normoxic (21% FIO(2)) and hyperoxic (100% FIO(2)) sensorimotor activation volumes were compared using Student's t-test. There were no significant differences between the primary somatosensory/primary motor/Brodmann area 40 (SI/MI/Ba40) and secondary somatosensory cortex (SII) activation volumes for normoxia and hyperoxia. (P>0.05). There was no difference between SI/MI/Ba40 and SII activations at 5 and 100 Hz. In contrast to results previously reported for primary visual cortex (V1), hyperoxia did not enhance sensorimotor cortical activation in area SI/MI/Ba40 or SII. These results indicate that there is regional heterogeneity of the fMRI response to hyperoxia in the cerebral cortex.

Successful treatment of spindle cell sarcoma of the sella turcica. Case report.

A primary spindle cell sarcoma of the sella turcica in a patient without a history of radiation treatment is a very rare occurrence. Only one other case has been reported to date, with local recurrence 7 months after the patient underwent subtotal resection and stereotactic radiosurgery of the tumor. The authors present a case of spindle cell sarcoma of the sella turcica successfully treated by surgery, external-beam radiotherapy, and gamma knife radiosurgery. After 24 months of follow up, the patient continues to show no evidence of disease.

A dorsolateral spinothalamic tract in macaque monkey.

Prior work has indicated the existence of a major spinal cord pathway made up of lamina I cell axons ascending in the dorsolateral funiculus in both rat and cat. In cat, a portion of this lamina I dorsolateral funiculus pathway terminates in the thalamus. The purpose of this report is to demonstrate that a similar dorsolateral spinothalamic tract exists in macaque monkey. Retrograde transport of horseradish peroxidase, injected into the somatosensory thalamus of monkeys, was used to identify the cells of origin of the spinothalamic tract in the cervical and lumbar enlargements. In order to determine the funicular courses of the axons contributing to the spinothalamic pathway, thalamic injections of horseradish peroxidase were combined with ipsilateral ventral or dorsolateral thoracic spinal cord lesions. The results indicate that in macaque monkey many lamina I cell axons ascend to the thalamus in the dorsolateral funiculus, contralateral to their parent cells. Some lamina I cell axons as well as the majority of axons of spinothalamic cells located in deeper laminae ascend in the contralateral ventral quadrant to terminate in the thalamus. The existence in macaque of a dorsolateral spinothalamic pathway comprised of lamina I cell axons strongly implies the presence of a similar pathway in humans and has important implications regarding the mechanisms underlying both clinical and experimental nociception.