Magnetic resonance-guided focused ultrasound unilateral thalamotomy for medically refractory essential tremor: 3-year follow-up data.

Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermediate (Vim) nucleus is an "incisionless" treatment for medically refractory essential tremor (ET). We present data on 49 consecutive cases of MRgFUS Vim thalamotomy followed-up for 3 years and review the literature on studies with longer follow-up data. Methods: A retrospective chart review of patients who underwent MRgFUS thalamotomy (January 2018-December 2020) at our institution was performed. Clinical Rating Scale for Tremor (CRST) and Quality of Life in Essential Tremor (QUEST) scores were obtained pre-operatively and at each follow-up with an assessment of side effects. Patients had post-operative magnetic resonance imaging within 24 h and at 1 month to figure out lesion location, size, and extent. The results of studies with follow-up ≥3 years were summarized through a literature review. Results: The CRST total (baseline: 58.6 ± 17.1, 3-year: 40.8 ± 18.0) and subscale scores (A + B, baseline: 23.5 ± 6.3, 3-year: 12.8 ± 7.9; C, baseline: 12.7 ± 4.3, 3-year: 5.8 ± 3.9) and the QUEST score (baseline: 38.0 ± 14.8, 3-year: 18.7 ± 13.3) showed significant improvement that was stable during the 3-year follow-up. Three patients reported tremor recurrence and two were satisfactorily retreated. Side effects were reported by 44% of patients (severe: 4%, mild and transient: 40%). The improvement in tremor and quality of life in our cohort was consistent with the literature. Conclusion: We confirmed the effectiveness and safety of MRgFUS Vim thalamotomy in medically refractory ET up to 3 years.

Microsurgical removal of supratentorial and cerebellar cavernous malformations: what has changed? A single institution experience.

BACKGROUND: Features associated with a safe surgical resection of cerebral cavernous malformations (CMs) are still not clear and what is needed to achieve this target has not been defined yet. METHODS: Clinical presentation, radiological features and anatomical locations were assessed for patients operated on from January 2008 to January 2018 for supratentorial and cerebellar cavernomas. Supratentorial CMs were divided into 3 subgroups (non-critical vs. superficial critical vs. deep critical). The clinical outcome was assessed through modified Rankin Scale (mRS) and was divided into favorable (mRS 0-1) and unfavorable (mRS ≥ 2). Post-operative epilepsy was classified according to the Maraire Scale. RESULTS: A total of 144 were considered eligible for the current study. At 6 months follow-up the clinical outcome was excellent for patients with cerebellar or lobar CMs in non-critical areas (mRS ≤ 1: 91.1 %) and for patients with superficial CMs in critical areas (mRS ≤ 1: 92.3 %). Patients with deep-seated suprantentorial CMs showed a favorable outcome in 76.9 %. As for epilepsy 58.5 % of patients presenting with a history of epilepsy were free from seizures and without therapy (Maraire grade I) at last follow-up (mean 3.9 years) and an additional 41.5 % had complete control of seizures with therapy (Maraire grade II). CONCLUSIONS: Surgery is safe in the management of CMs in non-critical but also in critical supratentorial locations, with a caveat for deep structures such as the insula, the basal ganglia and the thalamus/hypothalamus.

miRNAs in Serum Exosomes for Differential Diagnosis of Brain Metastases.

Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investigating their role in monitoring the response to therapy as well as the natural evolution of primary or secondary brain tumors. This study aimed to evaluate the modulation of the expression of three miRNAs, miR-21, miR-222 and miR-124-3p, in the serum exosomes of patients with high-grade gliomas (HGGs) and brain metastases (BMs) to verify their usefulness in the differential diagnosis of brain masses; then, it focused on their variations following the surgical and/or radiosurgical treatment of the BMs. A total of 105 patients with BMs from primary lung or breast cancer, or melanoma underwent neurosurgery or radiosurgery treatment, and 91 patients with HGGs were enrolled, along with 30 healthy controls. A significant increase in miR-21 expression in serum exosomes was observed in both HGGs and BMs compared with healthy controls; on the other hand, miR-124-3p was significantly decreased in BMs, and it was increased in HGGs. After the surgical or radiosurgical treatment of patients with BMs, a significant reduction in miR-21 was noted with both types of treatments. This study identified a signature of exosomal miRNAs that could be useful as a noninvasive complementary analysis both in the differential diagnosis of BMs from glial tumors and in providing information on tumor evolution over time.

The Immunohistochemical Loss of H3K27me3 in Intracranial Meningiomas Predicts Shorter Progression-Free Survival after Stereotactic Radiosurgery.

The immunohistochemical loss of histone H3 trimethylated in lysine 27 (H3K27me3) was recently shown to predict recurrence of meningiomas after surgery. However, its association with tumor progression after stereotactic radiosurgery (SRS) is unexplored. To investigate whether H3K27 methylation status may predict progression-free survival (PFS) after SRS, we assessed H3K27me3 immunoexpression in thirty-nine treatment naïve, intracranial, meningiomas, treated with surgery and subsequent SRS for residual (twenty-three cases) or recurrent (sixteen cases) disease. H3K27me3 immunostaining was lost in seven meningiomas, retained in twenty-seven and inconclusive in five. Six of the seven meningiomas (86%) with H3K27me3 loss had tumor progression after SRS, compared to nine of twenty-seven (33%) with H3K27me3 retention (p = 0.0143). In addition, patients harboring a meningioma with H3K27me3 loss had significantly shorter PFS after SRS (range: 10-81 months; median: 34 months), compared to patients featuring a meningioma with retained H3K27me3 (range: 9-143 months; median: 62 months) (p = 0.0036). Nonetheless, tumor sagittal location was the only significant prognostic variable at multivariate analysis for PFS after SRS (p = 0.0142). These findings suggest a previously unreported role of H3K27me3 as a predictor of meningioma progression after SRS for recurrent or residual disease. Modulation of H3K27 methylation status may represent a novel therapeutic strategy to induce radiosensitization of meningiomas.

Molecular Profiling of 22 Primary Atypical Meningiomas Shows the Prognostic Significance of 18q Heterozygous Loss and CDKN2A/B Homozygous Deletion on Recurrence-Free Survival.

The use of adjuvant therapy is controversial in atypical meningiomas with gross total resection. Predictors of recurrence risk could be useful in selecting patients for additional treatments. The aim of this study was to investigate whether molecular features are associated with recurrence risk of atypical meningiomas. According to WHO classification, the diagnosis of atypical meningioma was based on the presence of one major criteria (mitotic activity, brain invasion) or three or more minor criteria. The molecular profile of 22 cases (eight mitotically active, eight brain-invasive, and six with minor criteria) was assessed exploring the mutational status and copy number variation of 409 genes using next generation sequencing. Of the 22 patients with a median follow up of 53.5 months, 13 had recurrence of disease within 68 months. NF2 mutation was the only recurrent alteration (11/22) and was unrelated to clinical-pathological features. Recurring meningiomas featured a significantly higher proportion of copy number losses than non-recurring ones (p = 0.027). Chromosome 18q heterozygous loss or CDKN2A/B homozygous deletion was significantly associated with shorter recurrence-free survival (p = 0.008; hazard ratio: 5.3). Atypical meningiomas could be tested routinely for these genetic alterations to identify cases for adjuvant treatment.

A Risk Score Based on 5 Clinico-Pathological Variables Predicts Recurrence of Atypical Meningiomas.

The use of adjuvant radiotherapy is controversial in patients with atypical meningiomas treated with gross total resection (GTR). This study aimed to determine whether clinico-pathological features could be helpful to predict the recurrence risk in this group of patients and to identify high-risk ones who could benefit from adjuvant treatment. We collected 200 patients with primary atypical meningiomas treated with GTR but with no adjuvant radiotherapy from 5 different centers. A risk score, formulated by assigning 1 point for the presence and 0 points for the absence of 5 high-risk parameters (male sex, parasagittal site, Simpson grade 3, mitotic index ≥ 6/10 HPF, and sheeting), was the most significant predictor of recurrence. A score ≥2 was associated with 4.7 risk of shorter disease-free survival (p < 0.0001). Our findings indicate that the presence of at least 2 clinico-pathological high-risk factors predicts recurrence of totally resected primary atypical meningiomas and could be helpful for identifying patients who could benefit from adjuvant radiotherapy.

Italian consensus and recommendations on diagnosis and treatment of low-grade gliomas. An intersociety (SINch/AINO/SIN) document.

In 2018, the SINch (Italian Society of Neurosurgery) Neuro-Oncology Section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology Section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. For operational purposes, the Task Force was divided into five Working Groups: diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.

Long-term follow-up after surgical removal of meningioma of the inner third of the sphenoidal wing: outcome determinants and different strategies.

Meningioma arising in the inner third of the sphenoidal wing has been well recognized since the origin of neurosurgery, yet it still poses a formidable challenge for the surgeon. Treatment strategies can be optimized through a tailored approach to surgical timing and use of a non-surgical armamentarium. The aim of this study was to evaluate the long-term effect of different strategies on progression-free survival and overall survival. We examined the clinical records of brain tumor patients to assess determinants for surgery (extent of tumor removal, postoperative complications) and for progression-free survival and overall survival in relation to timing of surgery eventually followed by stereotactic radiosurgery (SRS). The records of 60 patients were retrospectively reviewed, from preoperative assessment to a median follow-up of 104 months. All were symptomatic with prevalently visual symptoms (42.2%), large tumors (median diameter 3.44 cm), extension into the cavernous sinus (38.3%), and severe vascular involvement of one or more encased or narrowed vessels (50%). Subtotal removal was achieved in 40% of cases, mainly determined by cavernous sinus and vascular involvement; neurological complications occurred in 18.3% (persistent in 6.7% due to oculomotor and vascular injury). The overall rate of symptom improvement was 32.3% at 3 months and 49.5% at 12 months. Radiological monitoring prevented clinical progression; tumor progression occurred in 11.7% of cases. There were significant differences in progression-free survival between patients with (median 46 months) and those without (median 104 months) recurrence (p = 0.002): 12.5% after total removal, 6.2% after subtotal removal and adjuvant SRS, and 28.5% after subtotal removal and observation. The related Kaplan-Meier survival curve showed no significant difference between the three strategies. Further, disease progression after recurrence was noted in 28.6% of cases, but overall survival was not influenced by either tumor recurrence or type of treatment. Treatment failure was recorded in four cases (6.7%): one perioperative death and three later on. Surgery is the mainstay for the treatment of symptomatic meningioma and to restore neurological function; however, resectability is limited by vascular and cavernous sinus involvement. Careful postoperative monitoring prevented clinical progression and adjuvant or adjunctive SRS proved effective in tumor control. A low surgical complication rate and excellent long-term outcomes were achieved with this strategy.

Magnetic resonance diffusion-tensor imaging metrics in High Grade Gliomas: Correlation with IDH1 gene status in WHO 2016 era.

PURPOSE: To evaluate any possible correlation between the presence of Isocitrate DeHydrogenase 1 mutation (IDH1m) and specific DTI (Diffusion Tensor Imaging) metrics, such as Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD). METHODS: We retrospectively analyzed 47 patients who underwent an advanced-MR study with DTI followed by surgical intervention with a subsequent histologic diagnosis of High-Grade Glioma (HGG) and immunohistochemical evaluation of IDH1 (Isocitrate DeHydrogenase) mutation status. For each DTI metrics we measured the ratio between tumor and normal tissue and we evaluated the correlation with IDH1 mutation. RESULTS: We observed a positive correlation with IDH1 status and RD and MD data. No correlation was demonstrated between IDH1 status and FA and AD. DISCUSSION: Our results support the hypothesis that the number of residual axonal fibers, extracellular matrix composition and the presence of colliquated tissue, may together contribute to a global RD increase in HGG, with a relatively higher increase in IDH1m tumors. CONCLUSIONS: Our data are in favor of a need for multimodal advance evaluation of HGG. DTI metrics help to analyze IDH1 mutation status, in order to better characterize the lesions and to tailor treatment and follow up.

Surgical Management of Adverse Radiation Effects After Gamma Knife Radiosurgery for Cerebral Arteriovenous Malformations: A Population-Based Cohort Study.

OBJECTIVE: The goal of this study is to report our experience in the surgical treatment of cerebral arteriovenous malformations (cAVMs) related permanent symptomatic adverse radiation effects (PSAREs), to clarify an appropriate surgical management and to identify the risk factors related to their development. METHODS: We evaluated 549 patients treated with Gamma Knife radiosurgery (GKRS) for cAVMs with a follow-up of at least 8 years. Univariate and multivariate analyses were used to test different risk factors related to the development of PSARE. We retrospectively reviewed the records of these patients to analyze the clinical outcome. RESULTS: Fourteen patients (2.5%) developed PSARE and were submitted to surgery. Higher average treated volume represents a significant risk factors for the development of PSARE (P < 0.05); on the other hand, older age and higher average dose reduce the risk of PSARE (P < 0.05). A favorable clinical outcome was achieved in 13 patients (93%) after surgery; in 1 patient, the unfavorable outcome was due to hemorrhage that occurred months after GKRS. Serial MRI scans following either surgical removal of the nodule or Ommaya reservoir positioning showed progressive reduction of brain edema in all cases. CONCLUSIONS: The management of PSARE is controversial, especially for cAVMs treated with SRS. Surgical removal is rarely needed, but-if unavoidable-it can be a valuable option in experienced hands. A careful preoperative planning is always necessary to detect pathologic blood flow through the PSARE.

Recurrent Atypical Meningiomas: Combining Surgery and Radiosurgery in One Effective Multimodal Treatment.

OBJECTIVE: Owing to their rarity and proteiform pathologic features, the clinical behavior of atypical meningiomas is not yet well characterized. Though the extent of resection is believed to be a key determinant of prognosis, limited data exist regarding optimal management of patients with recurrent disease. METHODS: In this 20-year retrospective case series, we reviewed the medical records of 46 patients with recurrent atypical meningiomas (185 lesions, 89 of which were local, 78 marginal, and 18 distant recurrences); treatment was radiosurgery (n = 60), surgery (n = 56), or both (n = 8). The median follow-up period was 53 months. Outcome measures were length of overall survival and disease-free intervals and prognostic factors for survival. RESULTS: Overall, the median progression-free survival was 26 months at the first recurrence and 100 months thereafter (the sum of the later intervals). Multivariate analysis showed that no treatment-related factors influenced prognosis, whereas recurrence at the skull base was a significant tumor-related factor limiting further treatment. Irrespective of treatment type, the recurrence-free interval was increasingly shorter during the clinical course, with a higher occurrence of marginal and distant lesions migrating to the midline and to the skull base. In sporadic cases, disease-free intervals were longer after wide craniotomy, tumor and dural resection with tumor-free margin. CONCLUSIONS: The disease-free interval was substantially similar after surgery and radiosurgery for treating recurrent disease in patients with atypical meningiomas. Surgery is the mainstay for prolonging survival, while radiosurgery can be an adjuvant strategy to gain time for clinical observation and planning aggressive surgical treatment.

Leksell Gamma Knife for pediatric and adolescent cerebral arteriovenous malformations: results of 100 cases followed up for at least 36 months.

OBJECT: The goal of this study was to evaluate advantages, risks, and failures of Gamma Knife radiosurgery (GKRS) in a large series of pediatric and adolescent patients with cerebral arteriovenous malformations (cAVMs) who were followed up for at least 36 months. METHODS: Since February 1993, 100 pediatric and adolescent patients (≤ 18 years of age) with cAVMs have undergone GKRS at the authors' institution and were followed up for at least 36 months. Forty-six patients were boys and 54 were girls; the mean age was 12.8 years (range 3-18 years). Hemorrhage, either alone or combined with seizure, was the clinical onset in 70% of cases. The mean pre-GK cAVM volume was 2.8 ml; 92% of cAVMs were Spetzler-Martin (S-M) Grades I-III. Most lesions (94%) were in eloquent or deep-seated brain regions, according to S-M classification. The parameters for mean and range in treatment planning were prescription isodose 53.8% (40%-90%); prescription dose (PD) 20.2 Gy (9.0-26.4 Gy); maximal dose (MD) 37.8 Gy (18-50 Gy); and number of shots 4.7 (1-17). On the day of GKRS, stereotactic CT or stereotactic MRI and digital subtraction angiography were used. RESULTS: Obliteration rate (OR) was angiographically documented in 75 of 84 cases (89.3%) after single-session GKRS, with actuarial ORs at 3 and 5 years of 68.0% and 88.1%, respectively. A repeat treatment was performed in 7 patients (6 with obliteration), and 16 patients with cAVMs underwent staged treatment (9 of them were angiographically cured). Thus, the overall OR was 90%, with actuarial ORs at 3, 5, and 8 years of 59.0%, 76.0%, and 85.0%, respectively. Permanent symptomatic GK-related complications were observed in 11% of cases, with surgical removal of enlarged mass seen on post-RS imaging needed in 5 cases. Hemorrhage during the latency period occurred in 9% of patients, but surgical evacuation of the hematoma was required in only 1 patient. One patient died due to rebleeding of a brainstem cAVM. Radiosurgery outcomes varied according to cAVM sizes and doses: volumes ≤ 10 ml and PDs > 16 Gy were significantly associated with higher ORs and lower rates of permanent complication and bleeding during the latency period. CONCLUSIONS: The data from this study reinforce the conclusion that GKRS is a safe and effective treatment for pediatric and adolescent cAVMs, yielding a high OR with minimal permanent severe morbidity and no mortality. The very low frequency of severe hemorrhages during the latency period further encourages a widespread application of RS in such patients. Univariate analysis found that modified RS-based cAVM score, nidus volume, PD, integral dose, S-M grade, and preplanned treatment (the last 2 parameters were also confirmed on multivariate analysis) significantly influenced OR. Lower S-M grades and single-session planned treatments correlated with shorter treatment obliteration interval on univariate analysis. This statistical analysis suggests that a staged radiosurgical treatment should be planned when nidus volume > 10 ml and/or when the recommended PD is ≤ 16 Gy.

The Role of 3T Magnetic Resonance Imaging for Targeting the Human Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease.

BACKGROUND: Chronic stimulation of the human subthalamic nucleus (STN) is gradually becoming accepted as a long-term therapeutic option for patients with advanced Parkinson disease (PD). 3Tesla (T) magnetic resonance imaging (MRI) improves contrast resolution in basal ganglia nuclei containing high levels of iron, because of magnetic susceptibility effects that increase significantly as the magnetic field gets higher. This phenomenon can be used for better visualization of the STN and may reduce the time necessary for detailed microrecording (MER) mapping, increasing surgery efficacy and lowering morbidity. OBJECTIVE: The objective of this retrospective study is to analyze a population of 20 deep brain stimulation (DBS) electrode implanted patients with PD divided into two groups in which different targeting methods were used. METHODS: Mean age was 56 years (range 37 to 69 years). Mean disease duration was 11.6 years. Mean follow-up was 12 months (range 6 to 36 months). Patients were divided into two groups: Group A contained 6 patients who underwent STN targeting using 1T stereotactic (T1w + T2w) MRI plus STN indirect atlas derived targeting. Group B consisted of 14 patients who underwent STN targeting using 3T nonstereotactic (T2w) MRI fused with 1T T1w stereotactic MRI and STN direct targeting. For statistical analysis, we compared (five different parameters in both (matched) groups: Unified Parkinson's disease rating scale (UPDRS) score reduction (medication off before surgery against stimulation on/medication off after surgery), postoperative drug reduction, duration of surgery, the "central preoperative track" chosen as final implantation track during surgery, and correspondence between the targeted STN and the intraoperative neurophysiologic data. RESULTS: Mean UPDRS III score reduction (medication off/stimulation on versus preoperative medication off) was 69% in Group A and 74% in Group B (p = 0.015, log-rank test) respectively. Postoperatively, antiparkinsonian treatment was reduced by 66% in Group A and 75% in Group B (p = 0.006, log-rank test). The preoperative "central" track (which corresponds to ideal STN targeting) proved to be the most clinically effective in 2/12 leads for Group A versus 21/28 for Group B (p < 0.001).Neurophysiologic data confirmed these results; the hypothetical target was confirmed by MER data in 76% of tracks in Group A, and in 75% of tracks in Group B (p < 0.001, univariate and multivariate analysis). CONCLUSION: 3T MRI appears to be a useful tool in STN-DBS preoperative targeting. Neurophysiologic testing remains fundamental to determine lead deepness (and prevent clinical side effects.

Radiosurgical options in neuro-oncology: a review on current tenets and future opportunities. Part II: adjuvant radiobiological tools.

Stereotactic radiosurgery (SRS) is currently a well-established, minimally invasive treatment for many primary and secondary tumors, especially deep-sited lesions for which traditional neurosurgical procedures were poorly satisfactory or not effective at all. The initial evolution of SRS was cautious, relying on more than 30 years of experimental and clinical work that preceded its introduction into the worldwide medical community. This path enabled a brilliant present, and the continuous pace of technological advancement holds promise for a brighter future. Part II of this review article will cover the impact of multimodal adjuvant technologies on SRS, and their input to the crucial role played by neurosurgeons, radiation oncologists and medical physicists in the management and care of fragile neuro-oncological patients.

The use of electrical source imaging in targeting lesional mesial temporal epilepsy for radiosurgical treatment.

Gamma knife radiosurgery (GK-RS) is a technique applied in selected cases of mesial-temporal epilepsy, although still limited to centres with adequate instrumentation and expertise. Here, we report a case of radio surgery targeted with the aid of electrical source imaging that localizes the cortical area generating the scalp epileptic discharges. The patient, a 39-year-old male, presented with a right mesio-temporal lesion; electrical source imaging localization partially overlapped with the lesional area but showed an important activation of the omolateral frontal area, concordant with the epileptic network. The patient underwent GK-RS, with good neurosurgical and clinical results. A radiosurgical ellipsoidal treatment volume area of 2 × 2 × 2 cm³, located over the right temporo-mesial region within a centre showing abnormal signal intensity, was considered. Seven months after treatment, the patient developed brain oedema that gradually resolved after one year. After three years of follow-up, the patient was seizure-free (Engel class I). Our very preliminary experience suggests that electrical source imaging appears to be a useful supporting tool for the definition of the radiosurgical treatment volume in selected patients with temporo-mesial lesional epilepsy.

Radiosurgical options in neuro-oncology: a review on current tenets and future opportunities. Part I: therapeutic strategies.

Stereotactic radiosurgery can nowadays be considered not only as a potential adjuvant to surgical treatment of several neuro-oncological pathologies, including primary tumors and metastatic lesions, but in some cases also as a valuable alternative tailored option. In Part I of the review, we propose a dissertation focused on the different irradiation stereotactic radiosurgery techniques to date available for clinical indications more relevant to oncologists and oncologic surgeons, such as high-grade and low-grade gliomas, metastases and meningiomas. It is noteworthy that the most recent body of literature correlated with this topic shows that the therapeutic results presently achievable are revolutionizing the way patients are diagnosed and managed worldwide. As we sought to shed light on the current potentialities of stereotactic radiosurgery, we must consider that to exploit all the benefits provided by this shift in clinical practice, a profound awareness by all practitioners involved in the care of neoplastic patients is certainly warranted.

Gamma Knife surgery in vestibular schwannomas: impact on the anterior and posterior labyrinth.

OBJECT: During the past decades, in small-to-medium size vestibular schwannomas, Gamma Knife surgery (GKS) has become a reliable therapeutic option because of either excellent local tumor control or minimal morbidity, with cranial neuropathy becoming increasingly rare. Although still insufficiently analyzed in larger cohorts of patients with long-term follow-ups, adequate chances of hearing preservation and vestibular sparing seem clinically guaranteed. However, deeper investigations are needed in this regard, expanding the number of cases and the follow-up period. METHODS: A small group of patients with vestibular schwannomas (74 patients, including 41 men and 33 women) treated between 2003 and 2009 using GKS at the authors' institution were analyzed--both before and after GKS--with computerized static stabilometry and electronystagmography for balance disorders, vertigo, and ataxia on 1 side and pure tone average, vocal speech discrimination score, auditory brainstem response, and so forth for hearing impairment and tinnitus on the other side. Eligibility criteria for this prospective study included previously untreated unilateral lesions and a Gardner-Robertson hearing class of I-III. Dosimetry plans had been programmed at the lower effective dosages for these tumors (median surface dose 12.4 Gy, range 10-13 Gy), carefully avoiding even minimal toxic dosages on the most vulnerable targets: the cochlea (never > 6 Gy) and the vestibular canals (< 7.5 Gy). RESULTS: To date, tumor growth control rates remain satisfactory; at a mean follow-up of 50 months, the rate was 96%. The overall level of hearing preservation was 72%, with 81% having Gardner-Robertson Class I hearing. Tinnitus decreased, from 52% to 28% of patients (p < 0.01). Significant improvements were also observed in vestibular symptoms, with computerized static stabilometry abnormalities decreasing from 62% to 32% (p < 0.001) and electronystagmography abnormalities reducing from 48% to 14% (p < 0.001). CONCLUSIONS: Using appropriate radiodosimetry planning, GKS seems to guarantee not only adequate tumor growth control rates, but also better levels of hearing preservation, with a documented, long-lasting improvement in vestibular functions.

Gamma knife radiosurgery for trigeminal neuralgia: results and potentially predictive parameters--part I: Idiopathic trigeminal neuralgia.

OBJECTIVE: Gamma knife radiosurgery (GKR) is an increasingly used, minimally invasive treatment option for patients with trigeminal neuralgia (TN) refractory to medical therapy. This retrospective study evaluates the long-term results and side effects of GKR in the treatment of TN focusing on potentially predictive factors. METHODS: One hundred sixty patients with TN were included in this study (minimum follow-up, >6 mo; mean, 37.4 mo; range, 6-144 mo). In 92 patients, GKR represented the first nonmedical option ("primary GKR"). In 68 patients, invasive treatments had been previously attempted. All patients were treated using a single 4-mm collimator shot targeting the pontine trigeminal root entry zone with a maximal dose of 75 to 95 Gy. Brainstem dose exposure never exceeded 15 Gy. Treatment outcome results were classified as Grade I (pain-free with no pharmacological treatment), Grade II (pain-free with pharmacological treatment), and Grade III (no result). Data were analyzed using the log-rank test for univariate analysis and the ordered logit model for multivariate analysis. RESULTS: In the overall series, 98 (61%) out of 160 patients reached a Grade I outcome, 45 (29%) reached a Grade II outcome, and 17 (10%) patients had no results from GKR. These results were encouraging for patients with typical facial pain features and for patients treated by a "primary" gamma knife. Considering the global outcome, the most effective and safest dose was found to be in the 80 to 90 Gy range. CONCLUSION: According to our experience, GKR represents a reliable second-line therapeutic approach for TN after pharmacological failure. Favorable prognostic factors include "primary GKR" and maximal GKR dose ranging between 80 and 90 Gy.