Therapeutic Effect of Human Adipocyte-derived Stem Cell-derived Exosomes on a Transgenic Mouse Model of Parkinson's Disease.

BACKGROUND/AIM: Stem cell therapy and regenerative medicine are promising for treating Parkinson's disease (PD) not only for the potential for cell replacement but also for the paracrine effect of stem cell secretion, especially proteins and nucleotide-enriched exosomes. This study investigated the neuroprotective effect of exosomes secreted from human adipocyte-derived stem cells (hADSCs) on PD. MATERIALS AND METHODS: hADSCs were isolated from the visceral fat tissue of individuals without PD who underwent bariatric surgery and were validated using surface markers and differentiation ability. Exosomes were isolated from the culture medium of hADSCs through serial ultracentrifugation and validated. Condensed exosomes were administered intravenously to 12-week-old MitoPark mice, transgenic parkinsonism mouse model with conditional knockout of mitochondrial transcription factor A in dopaminergic neurons, monthly for 3 months. Motor function, gait, and memory were assessed monthly, and immunohistochemical analysis of neuronal and inflammatory markers was performed at the end of the experiments. RESULTS: The hADSC-derived exosome-treated mice exhibited better motor function in beam walking and gait analyses than did the untreated mice. In the novel object recognition tests, the exosome-treated mice retained better memory function. Immunohistochemical analysis revealed that although exosome treatment did not prevent the loss of dopaminergic neurons in the substantia nigra of mice, it down-regulated microglial activation and neuroinflammation in the midbrain. CONCLUSION: hADSC-derived exosomes were neuroprotective in this in vivo mouse model of PD, likely because of their anti-inflammatory effect. Use of hADSC-derived exosomes may offer several beneficial effects in stem cell therapy. Since they can also be produced at an industrial level, they are a promising treatment option for PD and other neurodegenerative diseases.

Skull Base Meningiomas in Patients with Neurofibromatosis Type 2: An International Multicenter Study Evaluating Stereotactic Radiosurgery.

Objective Meningiomas are the second most common tumors in neurofibromatosis type 2 (NF-2). Microsurgery is challenging in NF-2 patients presenting with skull base meningiomas due to the intrinsic risks and need for multiple interventions over time. We analyzed treatment outcomes and complications after primary Gamma Knife radiosurgery (GKRS) to delineate its role in the management of these tumors. Methods An international multicenter retrospective study approved by the International Radiosurgery Research Foundation was performed. NF-2 patients with at least one growing and/or symptomatic skull base meningioma and 6-month follow-up after primary GKRS were included. Clinical and radiosurgical parameters were recorded for analysis. Results In total, 22 NF-2 patients with 54 skull base meningiomas receiving GKRS as primary treatment met inclusion criteria. Median age at GKRS was 38 years (10-79 years). Most lesions were located in the posterior fossa (55.6%). Actuarial progression free survival (PFS) rates were 98.1% at 2 years and 90.0% at 5 and 10 years. The median follow-up time after initial GKRS was 5.0 years (0.6-25.5 years). Tumor volume at GKRS was a predictor of tumor control. Lesions >5.5 cc presented higher chances to progress after radiosurgery ( p = 0.043). Three patients (13.64%) developed adverse radiation effects. No malignant transformation or death due to meningioma or radiosurgery was reported. Conclusions GKRS is effective and safe in the management of skull base meningiomas in NF-2 patients. Tumor volume deserve greater relevance during clinical decision-making regarding the most appropriate time to treat. GKRS offers a minimally invasive approach of particular interest in this specific group of patients.

Neurofibromatosis type 2-associated meningiomas: an international multicenter study of outcomes after Gamma Knife stereotactic radiosurgery.

OBJECTIVE: The management of neurofibromatosis type 2 (NF2)-associated meningiomas is challenging. The role of Gamma Knife radiosurgery (GKRS) in the treatment of these tumors remains to be fully defined. In this study, the authors aimed to examine the role of GKRS in the treatment of NF2-associated meningiomas and to evaluate the outcomes and complications after treatment. METHODS: Seven international medical centers contributed data for this retrospective cohort. Tumor progression was defined as a ≥ 20% increase from the baseline value. The clinical features, treatment details, outcomes, and complications were studied. The median follow-up was 8.5 years (range 0.6-25.5 years) from the time of initial GKRS. Shared frailty Cox regression was used for analysis. RESULTS: A total of 204 meningiomas in 39 patients treated with GKRS were analyzed. Cox regression analysis showed that increasing the maximum dose (p = 0.02; HR 12.2, 95% CI 1.287-116.7) and a lower number of meningiomas at presentation (p = 0.03; HR 0.9, 95% CI 0.821-0.990) were predictive of better tumor control in both univariable and multivariable settings. Age at onset, sex, margin dose, location, and presence of neurological deficit were not predictive of tumor progression. The cumulative 10-year progression-free survival was 94.8%. Radiation-induced adverse effects were noted in 4 patients (10%); these were transient and managed medically. No post-GKRS malignant transformation was noted in 287 person-years of follow-up. CONCLUSIONS: GKRS achieved effective tumor control with a low and generally acceptable rate of complications in NF2-associated meningiomas. There did not appear to be an appreciable risk of post-GKRS-induced malignancy in patients with NF2-treated meningiomas.

Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca2+ Channel Suppression: A Possible Neuroprotective Mechanism.

The glutamatergic neurotransmitter system has received substantial attention in research on the pathophysiology and treatment of neurological disorders. The study investigated the effect of the polyphenolic compound chlorogenic acid (CGA) on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). CGA inhibited 4-aminopyridine (4-AP)-induced glutamate release from synaptosomes. This inhibition was prevented in the absence of extracellular Ca2+ and was associated with the inhibition of 4-AP-induced elevation of Ca2+ but was not attributed to changes in synaptosomal membrane potential. In line with evidence observed through molecular docking, CGA did not inhibit glutamate release in the presence of P/Q-type Ca2+ channel inhibitors; therefore, CGA-induced inhibition of glutamate release may be mediated by P/Q-type Ca2+ channels. CGA-induced inhibition of glutamate release was also diminished by the calmodulin and Ca2+/calmodilin-dependent kinase II (CaMKII) inhibitors, and CGA reduced the phosphorylation of CaMKII and its substrate, synapsin I. Furthermore, pretreatment with intraperitoneal CGA injection attenuated the glutamate increment and neuronal damage in the rat cortex that were induced by kainic acid administration. These results indicate that CGA inhibits glutamate release from cortical synaptosomes by suppressing P/Q-type Ca2+ channels and CaMKII/synapsin I pathways, thereby preventing excitotoxic damage to cortical neurons.

Iatrogenic pseudoaneurysm of the superficial temporal artery following craniectomy from a scalp hook retractor penetrating injury: Case report and literature review.

BACKGROUND: Iatrogenic pseudoaneurysms in scalp vessels are an uncommon complication after cranial surgery. This paper reports a case of scalp pseudoaneurysm in the superficial temporal artery (STA) after forceful hook retraction in craniectomy and reviews the relevant literature. CASE DESCRIPTION: A 36-year-old man with history of hypertension and depression presented to the emergency department with head injury after using sedation medication. Brain computed tomography (CT) revealed a 2-cm-thick right parietal extradural hematoma (EDH) with parietal skull fracture, a bilateral lower frontotemporal contusional intracerebral hematoma, diffuse subarachnoid hemorrhage, and a right frontotemporoparietal subdural hematoma. To prevent EDH progression, frontotemporal emergency craniectomy to remove the EDH was performed. The next day, a firm, painful mass measuring 3 × 3.5 cm2 was discovered over the right frontal scalp. The mass was close to the site where the scalp hook retractor had been placed during surgery. Sonography revealed pulsatile blood flow with an arterial feeder inside the mass. CT angiography revealed a 1 × 1.2 × 0.7 cm3 pseudoaneurysm in the right frontal scalp from the frontal branch of the STA. We scheduled a resection of the pseudoaneurysm and combined cranioplasty on the 29th postoperative day. The pseudoaneurysm was resected en bloc. The patient was discharged with clear consciousness and intact muscle power. CONCLUSION: The complications of STA pseudoaneurysms caused by scalp hook retractors are rare and not yet well reported. Surgeons must avoid injuring the STA when using a scalp hook retractor.

Convexity Meningiomas in Patients with Neurofibromatosis Type 2: Long-Term Outcomes After Gamma Knife Radiosurgery.

BACKGROUND: Convexity meningiomas are common tumors requiring treatment in patients with neurofibromatosis type 2 (NF2). Although different therapeutic options are described for sporadic convexity meningioma, much less is known about these lesions in patients with NF2 despite their distinct biology and need for multiple treatments. We analyzed the value of Gamma Knife radiosurgery (GKRS) as definitive treatment for convexity meningiomas in patients with NF2. METHODS: This international multicenter retrospective study was approved by the International Radiosurgery Research Foundation. Patients with NF2 with at least 1 convexity meningioma and 6-month follow-up after primary GKRS were included. RESULTS: Inclusion criteria were met by 18 patients with NF2. A total of 120 convexity meningiomas (median treatment volume, 0.66 cm3 [range, 0.10-21.20 cm3]) were analyzed. Median follow-up after initial GKRS was 15.6 years (range, 0.6-25.5 years). Median age at GKRS was 32.5 years (range, 16-53 years). Median number of meningiomas per patient was 13 (range, 1-27), and median number of convexity lesions receiving GKRS per patient was 3.5 (range, 1-27). One case of tumor progression was reported 24 years after GKRS, leading to actuarial progression-free survival rates of 100% at 2, 5, and 10 years. No malignant transformation or death due to meningioma or radiosurgery was recorded. CONCLUSIONS: GKRS is safe and effective as definitive treatment of small to medium-sized convexity meningiomas in patients with NF2. Despite concerns about the particular mutational burden of these tumors, no malignant transformation manifested after treatment. GKRS represents a minimally invasive option that offers long-term tumor control to this specific group of patients.

Earlier radiosurgery leads to better pain relief and less medication usage for trigeminal neuralgia patients: an international multicenter study.

OBJECTIVE: Trigeminal neuralgia (TN) is a chronic pain condition that is difficult to control with conservative management. Furthermore, disabling medication-related side effects are common. This study examined how stereotactic radiosurgery (SRS) affects pain outcomes and medication dependence based on the latency period between diagnosis and radiosurgery. METHODS: The authors conducted a retrospective analysis of patients with type I TN at 12 Gamma Knife treatment centers. SRS was the primary surgical intervention in all patients. Patient demographics, disease characteristics, treatment plans, medication histories, and outcomes were reviewed. RESULTS: Overall, 404 patients were included. The mean patient age at SRS was 70 years, and 60% of the population was female. The most common indication for SRS was pain refractory to medications (81%). The median maximum radiation dose was 80 Gy (range 50-95 Gy), and the mean follow-up duration was 32 months. The mean number of medications between baseline (pre-SRS) and the last follow-up decreased from 1.98 to 0.90 (p < 0.0001), respectively, and this significant reduction was observed across all medication categories. Patients who received SRS within 4 years of their initial diagnosis achieved significantly faster pain relief than those who underwent treatment after 4 years (median 21 vs 30 days, p = 0.041). The 90-day pain relief rate for those who received SRS ≤ 4 years after their diagnosis was 83.8% compared with 73.7% in patients who received SRS > 4 years after their diagnosis. The maximum radiation dose was the strongest predictor of a durable pain response (OR 1.091, p = 0.003). Early intervention (OR 1.785, p = 0.007) and higher maximum radiation dose (OR 1.150, p < 0.0001) were also significant predictors of being pain free (a Barrow Neurological Institute pain intensity score of I-IIIA) at the last follow-up visit. New sensory symptoms of any kind were seen in 98 patients (24.3%) after SRS. Higher maximum radiation dose trended toward predicting new sensory deficits but was nonsignificant (p = 0.075). CONCLUSIONS: TN patients managed with SRS within 4 years of diagnosis experienced a shorter interval to pain relief with low risk. SRS also yielded significant decreases in adjunct medication utilization. Radiosurgery should be considered earlier in the course of treatment for TN.

Stereotactic radiosurgery for central neurocytomas: an international multicenter retrospective cohort study.

OBJECTIVE: Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors. METHODS: The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated. RESULTS: The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022). CONCLUSIONS: Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.

Stereotactic Radiosurgery for Cavernous Sinus Versus Noncavernous Sinus Dural Arteriovenous Fistulas: Outcomes and Outcome Predictors.

BACKGROUND: Dural arteriovenous fistulas (DAVFs) can be categorized based on location. OBJECTIVE: To compare stereotactic radiosurgery (SRS) outcomes between cavernous sinus (CS) and non-CS DAVFs and to identify respective outcome predictors. METHODS: This is a retrospective study of DAVFs treated with SRS between 1988 and 2016 at 10 institutions. Patients' variables, DAVF characters, and SRS parameters were included for analyses. Favorable clinical outcome was defined as angiography-confirmed obliteration without radiological radiation-induced changes (RIC) or post-SRS hemorrhage. Other outcomes were DAVFs obliteration and adverse events (including RIC, symptomatic RIC, and post-SRS hemorrhage). RESULTS: The overall study cohort comprised 131 patients, including 20 patients with CS DAVFs (15%) and 111 patients with non-CS DAVFs (85%). Rates of favorable clinical outcome were comparable between the 2 groups (45% vs 37%, P = .824). Obliteration rate after SRS was higher in the CS DAVFs group, even adjusted for baseline difference (OR = 4.189, P = .044). Predictors of favorable clinical outcome included higher maximum dose (P = .014) for CS DAVFs. Symptomatic improvement was associated with obliteration in non-CS DAVFs (P = .005), but symptoms improved regardless of whether obliteration was confirmed in CS DAVFs. Non-CS DAVFs patients with adverse events after SRS were more likely to be male (P = .020), multiple arterial feeding fistulas (P = .018), and lower maximum dose (P = .041). CONCLUSION: After SRS, CS DAVFs are more likely to obliterate than non-CS ones. Because these 2 groups have different total predictors for clinical and radiologic outcomes after SRS, they should be considered as different entities.

A Proposed Grading Scale for Predicting Outcomes After Stereotactic Radiosurgery for Dural Arteriovenous Fistulas.

BACKGROUND: There are presently no grading scales that specifically address the outcomes of cranial dural arteriovenous fistula (dAVF) after stereotactic radiosurgery (SRS). OBJECTIVE: To design a practical grading system that would predict outcomes after SRS for cranial dAVFs. METHODS: From the International Radiosurgery Research Foundation (University of Pittsburgh [41 patients], University of Pennsylvania [6 patients], University of Sherbrooke [2 patients], University of Manitoba [1 patient], West Virginia University [2 patients], University of Puerto Rico [1 patient], Beaumont Health System 1 [patient], Na Homolce Hospital [13 patients], the University of Virginia [48 patients], and Yale University [6 patients]) centers, 120 patients with dAVF treated with SRS were included in the study. The factors predicting favorable outcome (obliteration without post-SRS hemorrhage) after SRS were assessed using logistic regression analysis. These factors were pooled with the factors that were found to be predictive of obliteration from 7 studies with 736 patients after a systematic review of literature. These were entered into stepwise multiple regression and the best-fit model was identified. RESULTS: Based on the predictive model, 3 factors emerged to develop an SRS scoring system: cortical venous reflux (CVR), prior intracerebral hemorrhage (ICH), and noncavernous sinus location. Class I (score of 0-1 points) predicted the best favorable outcome of 80%. Class II patients (2 points score) had an intermediate favorable outcome of 57%, and class III (score 3 points) had the least favorable outcome at 37%. The ROC analysis showed better predictability to prevailing grading systems (AUC = 0.69; P = .04). Kaplan-Meier analysis showed statistically significant difference between the 3 subclasses of the proposed grading system for post-SRS dAVF obliteration (P = .001). CONCLUSION: The proposed dAVF grading system incorporates angiographic, anatomic, and clinical parameters and improves the prediction of the outcomes following SRS for dAVF as compared to the existing scoring systems.

Changes in the muscles of mastication before and after primary stereotactic radiosurgery in patients with idiopathic trigeminal neuralgia.

OBJECTIVE: The motor root of the trigeminal nerve runs close to the sensory root and receives considerable radiation during Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The object of this study was to evaluate via MRI the changes in the muscles of mastication before and after upfront GKRS in patients with idiopathic TN. METHODS: In this single-institution retrospective cohort study, all patients with idiopathic unilateral TN treated with primary GKRS at the University of Virginia in the period from 2007 to 2017 were included provided that they had pre- and post-GKRS MRI data. The thicknesses of the temporalis, pterygoid, and masseter muscles were measured on both pre- and post-GKRS MRI in a blinded fashion. Changes in the muscles like fatty infiltration, MRI signal, or atrophy were noted. RESULTS: Among the 68 patients eligible for inclusion in the study, 136 temporalis muscles, 136 medial pterygoid muscles, 136 lateral pterygoid muscles, and 136 masseter muscles were assessed. A subset of patients was found to have muscle atrophy even prior to GKRS. Pre-GKRS atrophy of the masseter, medial pterygoid, lateral pterygoid, and temporalis muscles was seen in 18 (26%), 16 (24%), 9 (13%), and 16 (24%) patients, respectively. Logistic regression analysis showed that distribution of pain in the V3 territory (p = 0.01, OR 5.43, 95% CI 1.46-20.12) and significant pain on chewing (p = 0.02, OR 5.32, 95% CI 1.25-22.48) were predictive of pre-GKRS atrophy. Reversal of atrophy of these muscles occurred after GKRS in a majority of the patients. The incidence of new-onset permanent post-GKRS muscle atrophy was 1.5%. The median follow-up was 39 months (range 6-108 months). CONCLUSIONS: A subset of patients with TN with significant pain on chewing have pre-GKRS disuse atrophy of the muscles of mastication. A reversal of the atrophy occurs in a majority of the patients following GKRS. New-onset motor neuropathy post-GKRS was rare.

The impact of preradiosurgery embolization on intracranial arteriovenous malformations: a matched cohort analysis based on de novo lesion volume.

OBJECTIVE: The benefits and risks of pre-stereotactic radiosurgery (SRS) embolization have been reported in different studies. The goal of this study was to compare the long-term outcome of arteriovenous malformations (AVMs) treated with and without pre-SRS embolization. METHODS: A database including 1159 patients with AVMs who underwent SRS was reviewed. The embolized group was selected by including AVMs with pre-SRS embolization, maximal diameter > 30 mm, and estimated volume > 8 ml. The nonembolized group was defined as AVMs treated by SRS alone with matched de novo nidus volume. Outcomes including incidences of favorable clinical outcome (obliteration without hemorrhage, cyst formation, worsening, or new seizures), obliteration, adverse effects, and angioarchitectural complexity were evaluated. RESULTS: The study cohort comprised 17 patients in the embolized group (median AVM volume 17.0 ml) and 35 patients in the nonembolized group (median AVM volume 13.1 ml). The rates of obliteration (embolized cohort: 33%, 44%, and 56%; nonembolized cohort: 32%, 47%, and 47% at 4, 6, and 10 years, respectively) and favorable outcome were comparable between the 2 groups. However, the embolized group had a significantly higher incidence of repeat SRS (41% vs 23%, p = 0.012) and total procedures (median number of procedures 4 vs 1, p < 0.001), even with a significantly higher margin dose delivered at the first SRS (23 Gy vs 17 Gy, p < 0.001). The median angioarchitectural complexity score was reduced from 7 to 5 after embolization. Collateral flow and neovascularization were more frequently observed in the embolized nonobliterated AVMs. CONCLUSIONS: Both embolization plus SRS and SRS alone were effective therapies for moderately large (8-39 ml) AVMs. Even with a significantly higher prescription dose at the time of initial SRS, the embolized group still required more procedures to reach final obliteration. The presence of collateral flow and neovascularization could be risk factors for a failure to obliterate following treatment.

The benefit and risk of stereotactic radiosurgery for prolactinomas: an international multicenter cohort study.

OBJECTIVE: The most common functioning pituitary adenoma is prolactinoma. Patients with medically refractory or residual/recurrent tumors that are not amenable to resection can be treated with stereotactic radiosurgery (SRS). The aim of this multicenter study was to evaluate the role of SRS for treating prolactinomas. METHODS: This retrospective study included prolactinomas treated with SRS between 1997 and 2016 at ten institutions. Patients' clinical and treatment parameters were investigated. Patients were considered to be in endocrine remission when they had a normal level of prolactin (PRL) without requiring dopamine agonist medications. Endocrine control was defined as endocrine remission or a controlled PRL level ≤ 30 ng/ml with dopamine agonist therapy. Other outcomes were evaluated including new-onset hormone deficiency, tumor recurrence, and new neurological complications. RESULTS: The study cohort comprised 289 patients. The endocrine remission rates were 28%, 41%, and 54% at 3, 5, and 8 years after SRS, respectively. Following SRS, 25% of patients (72/289) had new hormone deficiency. Sixty-three percent of the patients (127/201) with available data attained endocrine control. Three percent of patients (9/269) had a new visual complication after SRS. Five percent of the patients (13/285) were recorded as having tumor progression. A pretreatment PRL level ≤ 270 ng/ml was a predictor of endocrine remission (p = 0.005, adjusted HR 0.487). An increasing margin dose resulted in better endocrine control after SRS (p = 0.033, adjusted OR 1.087). CONCLUSIONS: In patients with medically refractory prolactinomas or a residual/recurrent prolactinoma, SRS affords remarkable therapeutic effects in endocrine remission, endocrine control, and tumor control. New-onset hypopituitarism is the most common adverse event.

Impact of Integral Dose on the Maintenance of Pain Relief in Patients with Idiopathic Trigeminal Neuralgia Treated with Upfront Gamma Knife Radiosurgery.

BACKGROUND: Integral dose (ID) defined as the product of mean dose and target volume, is a measure of the absorbed radiation energy. OBJECTIVE: To evaluate the effect of ID on the duration of pain relief after primary Gamma knife stereotactic radiosurgery (GKSRS) in trigeminal neuralgia. PATIENTS AND METHODS: A total of 78 patients who achieved initial pain response of I-III on the Barrow Neurological Institute Pain Scale (BNI-PS) following primary GKSRS for idiopathic trigeminal neuralgia were included in this study. A Cox regression model was used to compute the prognostic factor with respect to the ID within the 50% isodose line. Facial pain relief maintenance interval was defined as time interval between the day of improved BNI-PS grade and pain level back to the BNI-PS IV or V. The median duration of follow-up was 42 months (range 6-108 months). RESULTS: After the initial GKSRS, patients achieved pain relief at a median of 0.5 months (range, 7 days to 6 months); 28 patients developed recurrence of pain. There was a positive correlation between the pain relief maintenance and increasing ID within 50% isodose line (hazard ratio 1.85, P = 0.04) on multivariable Cox-regression analysis. Using logistic regression analysis, we found that ID was not predictive of developing post-stereotactic radiosurgery hypoesthesia (P = 0.64, hazard ratio 1.057). CONCLUSIONS: Stereotactic radiosurgery can be individualized based on trigeminal nerve morphology to achieve durable pain relief in patients with trigeminal neuralgia. ID calculation aids in planning an optimal radiation dose based on the nerve morphology to provide durable pain relief of idiopathic trigeminal neuralgia.

Gamma knife radiosurgery for the treatment of cavernous sinus meningiomas: post-treatment long-term clinical outcomes, complications, and volume changes.

PURPOSE: To evaluate the outcomes of patients who underwent Gamma Knife radiosurgery (GKRS) for the treatment of cavernous sinus (CS) meningiomas. METHODS: We retrospectively reviewed the clinical and radiological outcomes of 95 patients with CS meningiomas at Taipei Veterans General Hospital between 1993 and 2011. The study cohort comprised 27 men and 68 women with a median age of 50 years (range 29-79 years). The median pre-GKRS tumor volume was 6.6 ml (range 0.9-35.7 ml). The median margin dose was 12 Gy (range 11-21 Gy). The clinical factors related to favorable outcomes were assessed. RESULTS: The median follow-up period was 59 (range 12-209) months. At the final follow-up, the tumor volume regressed in 70 patients (74%) and progressed in eight (8%). Kaplan-Meier analysis revealed that the progression-free survival rates at 5 and 10 years were 92.7% and 81.2%, respectively. Three patients (3.2%) experienced exacerbated cranial nerve dysfunction following radiosurgery. Confined tumors were found to be an independent prognostic factor for tumor control and shorter times to regression in the multivariable analyses. No risk factor for tumor progression was identified in either the univariate or multivariate analyses. CONCLUSIONS: GKRS provides good long-term tumor control and is associated with low cranial nerve-related morbidity development rates in patients with small- to medium-sized CS meningiomas. Confined tumor could be an independent prognostic factor for tumor control and shorter times to regression in multivariate analysis. Life-long follow-up is mandatory in such settings, even for outpatients with shrunken or stabilized tumors.

Primary versus postoperative stereotactic radiosurgery for acromegaly: a multicenter matched cohort study.

OBJECTIVE: The role of primary stereotactic radiosurgery (SRS) in patients with medically refractory acromegaly who are not operative candidates or who refuse resection is poorly understood. The aim of this multicenter, matched cohort study was to compare the outcomes of primary versus postoperative SRS for acromegaly. METHODS: The authors reviewed an International Radiosurgery Research Foundation database of 398 patients with acromegaly who underwent SRS and categorized them into primary or postoperative cohorts. Patients in the primary SRS cohort were matched, in a 1:2 ratio, to those in the postoperative SRS cohort, and the outcomes of the 2 matched cohorts were compared. RESULTS: The study cohort comprised 78 patients (median follow-up 66.4 months), including 26 and 52 in the matched primary and postoperative SRS cohorts, respectively. In the primary SRS cohort, the actuarial endocrine remission rates at 2 and 5 years were 20% and 42%, respectively. The Cox proportional hazards model showed that a lower pre-SRS insulin-like growth factor-1 level was predictive of initial endocrine remission (p = 0.03), whereas a lower SRS margin dose was predictive of biochemical recurrence after initial remission (p = 0.01). There were no differences in the rates of radiological tumor control (p = 0.34), initial endocrine remission (p = 0.23), biochemical recurrence after initial remission (p = 0.33), recurrence-free survival (p = 0.32), or hypopituitarism (p = 0.67) between the 2 matched cohorts. CONCLUSIONS: Primary SRS has a reasonable benefit-to-risk profile for patients with acromegaly in whom resection is not possible, and it has similar outcomes to endocrinologically comparable patients who undergo postoperative SRS. SRS with medical therapy in the latent period can be used as an alternative to surgery in selected patients who cannot or do not wish to undergo resection.

A Propensity Score-Matched Cohort Analysis of Outcomes After Stereotactic Radiosurgery in Older versus Younger Patients with Dural Arteriovenous Fistula: An International Multicenter Study.

OBJECTIVE: This study aims to evaluate the outcomes of Gamma Knife stereotactic radiosurgery (SRS) for dural arteriovenous fistulas (dAVFs) in older patients (≥65 years) compared with younger patients (age <65 years). METHODS: Two groups with a total of 96 patients were selected from a database of 133 patients with dAVF from 9 international medical centers with a minimum 6 months follow-up. A 1:2 propensity matching was performed by nearest-neighbor matching criteria based on sex, Borden grade, maximum radiation dose given, and location. The older cohort consisted of 32 patients and the younger cohort consisted of 64 patients. The mean overall follow-up in the combined cohort was 42.4 months (range, 6-210 months). RESULTS: In the older cohort, a transverse sinus location was found to significantly predict dAVF obliteration (P = 0.01). The post-SRS actuarial 3-year and 5-year obliteration rates were 47.7% and 78%, respectively. There were no cases of post-SRS hemorrhage. In the younger cohort, the cavernous sinus location was found to significantly predict obliteration (P = 0.005). The 3-year and 5-year actuarial obliteration rates were 56% and 70%, respectively. Five patients (7.8%) hemorrhaged after SRS. Margin dose ≥25 Gy was predictive of unfavorable outcome. The obliteration rate (P = 0.3), post-SRS hemorrhage rate (P = 0.16), and persistent symptoms after SRS (P = 0.83) were not statistically different between the 2 groups. CONCLUSIONS: SRS achieves obliteration in most older patients with dAVF, with an acceptable rate of complication. There was no increased risk of postradiosurgery complications in the older cohort compared with the younger patients.

Endoscopic hematoma evacuation in patients with spontaneous supratentorial intracerebral hemorrhage.

BACKGROUND: Surgical evacuation of spontaneous supratentorial intracerebral hemorrhage (ICH) is controversial because the traditional surgical approach sometimes causes further brain injury. The introduction of the neuroendoscope has brought with it the new idea of minimal invasiveness, which may improve the surgical results of ICH. METHODS: Twenty-one patients with spontaneous supratentorial ICH underwent endoscopic hematoma evacuation between December 2010 and January 2012. Safe entry points could be Kocher's, Keen's, or Frazier's point, depending on the locations of the hemorrhages. The surgical steps were as follows: (1) cortical incision and dilation of the channel; (2) introduction of the transparent sheath; (3) gushing out of the hematoma under high intracranial pressure; (4) changing the angle of the transparent sheath, endoscope, and suction tip to remove residual hematoma; and (5) paving a layer of hemostatic agents after hematoma removal. RESULTS: The median operative time was 120 minutes (range: 90-190 minutes), and the median blood loss was 160 mL (range: 50-300 mL). The median duration of intensive care unit stay was 6 days (range: 2-18 days). The median hematoma evacuation ratio was 90% (range: 60-99%). Two patients had rebleeding events, and the mortality rate was 9.5% (n = 2/21). The median Glasgow Coma Scale score improved from 8 to 11 within 1 week after surgery, and the median Glasgow Outcome Scale score was 3 after 6 months and 12 months follow-up. CONCLUSION: With the introduction of the minimally invasive techniques and the evolution of the neuroendoscope and hemostatic agents, the median operative time and blood loss have been significantly decreased. Although the hematoma evacuation rates were similar between the endoscope (90%) and craniotomy (85%) groups, the median intensive care unit stay was decreased from 11 days to 6 days due to reduced surgical invasiveness. This represents an important advancement in treating spontaneous supratentorial ICH, and provides a measured preview of the promising results that can be expected in the future.

Gamma Knife surgery for craniopharyngioma: report on a 20-year experience.

OBJECT: Although craniopharyngiomas are benign intracranial tumors, their high recurrence rates and intimate associations with surrounding neurovascular structures make gross tumor resection challenging. Stereotactic radiosurgery has been introduced as a valuable adjuvant therapy for recurrent or residual craniopharyngiomas. However, studies with large patient populations documenting long-term survival and progression-free survival rates are rare in the literature. The current study aims to report the long-term radiosurgical results and to define the prognostic factors in a large cohort of patients with a craniopharyngioma. METHODS: A total of 137 consecutive patients who underwent 162 sessions of Gamma Knife surgery (GKS) treatments at the Taipei Veterans General Hospital between 1993 and 2012 were analyzed. The patients' median age was 30.1 years (range 1.5-84.9 years), and the median tumor volume was 5.5 ml (range 0.2-28.4 ml). There were 23 solid (16.8%), 23 cystic (16.8%), and 91 mixed solid and cystic (66.4%) craniopharyngiomas. GKS was indicated for residual or recurrent craniopharyngiomas. The median radiation dose was 12 Gy (range 9.5-16.0 Gy) at a median isodose line of 55% (range 50%-78%). RESULTS: At a median imaging follow-up of 45.7 months after GKS, the rates of tumor control were 72.7%, 73.9%, and 66.3% for the solid, cystic, and mixed tumors, respectively. The actuarial progression-free survival rates plotted by the Kaplan-Meier method were 70.0% and 43.8% at 5 and 10 years after radiosurgery, respectively. After repeated GKS, the actuarial progression-free survival rates were increased to 77.3% and 61.2% at 5 and 10 years, respectively. The overall survival rates were 91.5% and 83.9% at the 5- and 10-year follow-ups, respectively. Successful GKS treatment can be predicted by tumor volume (p = 0.011). Among the 137 patients who had clinical follow-up, new-onset or worsened pituitary deficiencies were detected in 11 patients (8.0%). Two patients without tumor growth had a worsened visual field, and 1 patient had a new onset of third cranial nerve palsy. CONCLUSIONS: The current study suggests that GKS is a relatively safe modality for the treatment of recurrent or residual craniopharyngiomas, and it is associated with improved tumor control and reduced in-field recurrence rates. Acceptable rates of complications occurred.

Radiosurgery target location and individual anatomical variation in trigeminal nerves.

OBJECT: The authors evaluated individual anatomical variations in the trigeminal nerves of patients with medically intractable trigeminal neuralgia and clarified the relationships among the variations, radiosurgical target locations, and the clinical outcomes after high-dose Gamma Knife surgery (GKS). METHODS: From 2006 through 2011, the authors conducted a retrospective review of 106 cases of primary or secondary trigeminal neuralgia consecutively treated with GKS targeting the dorsal root entry zone (DREZ) for which a maximal dose of 90 Gy and a 20% isodose line to the brainstem were used. A questionnaire was used to evaluate patients' pre- and post-GKS clinical conditions. To evaluate individual anatomical variations among trigeminal nerves, the authors used 3 parameters: the length of the trigeminal nerve in the cistern (nerve length), the length of the target between the radiation shot and the brainstem (targeting length), and the ratio between nerve length and targeting length (targeting ratio). RESULTS: The median length of the trigeminal nerves in the 106 patients was 9.6 mm (range 6.04-20.74 mm), the median targeting length was 3.8 mm (range 1.81-10.84 mm), and the median targeting ratio was 38% (range 13%- 80%). No statistically significant differences in pain relief and pain recurrence were detected among patients with these various nerve characteristics. However, radiation-induced facial hypesthesia correlated with nerve length and targeting ratio (p < 0.05) but not with absolute distance from the brainstem (targeting length). CONCLUSIONS: In trigeminal neuralgia patients who received DREZ-targeted GKS, the rate of pain relief did not differ according to anatomical nerve variations. However, the frequency of facial hypesthesia was higher among patients in whom the nerve was longer (> 11 mm) or the targeting ratio was lower (< 36%). Adjusting the target according to the targeting ratio, especially for patients with longer nerves, can reduce facial hypesthesia and enable maintenance of effective pain control.