Dual-Target Radiosurgery for Concomitant Continuous Pain Presentation of Trigeminal Neuralgia: Radiomodulation Effect and Dose.

OBJECTIVES: Patients with trigeminal neuralgia (TN) experience concomitant continuous pain (CCP) that can be difficult to treat. A dual-target approach delivering a high dose of radiation to the nerve and the contralateral thalamus can develop a fast radiomodulation effect on lowering pain. We sought to determine if this effect was dose dependent. METHODS: We retrospectively reviewed 21 patients treated with radiosurgery in CCP and severe TN pain, with a visual analog scale (VAS) score of nine out of 10 at the time of treatment. Ten patients were treated with a high dose (>120 Gy) in the thalamus 90 Gy to the nerve, and the rest with a low dose (<120 Gy) to the thalamus and >90 Gy to the nerve. RESULTS: Of those who received the high dose to the thalamus, six patients (60%) received 140 Gy, and four (40%) received 120 Gy, with a median dose to the trigeminal nerve of 90 and 85 Gy, respectively. The high thalamus dose showed a radiomodulation effect from day 1. The low thalamus dose did not produce radiomodulation on any of the first four days. The percentage of VAS score reduction one month after treatment was higher in the high-thalamus dose group than in the low-thalamus dose group. At three months, VAS score was 2 in the high-dose group and 4 in the low-dose group. CONCLUSIONS: The radiomodulation effect in pain and dual-target radiosurgery is dose dependent in CCP in TN; a high dose can provide a more consistent clinical result than a lower dose.

Upfront Radiosurgery for Treatment of Symptomatic Obstructive Hydrocephalus due to Brain Tumors.

Introduction Hydrocephalus is a build-up of cerebrospinal fluid (CSF) in the brain and is characterized by abnormal dilatation of the cerebral ventricles. Patients can be either asymptomatic, have symptoms related to primary tumors, or have hydrocephalus-related symptoms. Generally, symptomatic patients are candidates for ventriculoperitoneal (VP) shunt placement to reduce acute symptoms. Little evidence exists regarding the resolution of symptomatic hydrocephalus secondary to brain tumors using stereotactic radiosurgery (SRS) alone as a primary treatment option. Methods The present study is a retrospective series of eight patients (six men and two women) diagnosed with obstructive hydrocephalus due to brain tumors treated with radiosurgery between April 2013 and February 2021. The primary endpoint of the present study is to report our institutional experience regarding the control of symptomatic obstructive hydrocephalus due to brain tumors treated with upfront radiosurgery. Results The mean age was 52 years (range, 5-79). The most common presenting symptoms included headache (100%), vision-related symptoms (75%), and ataxia (37.5%). All patients showed symptom improvement after radiosurgery, five (62.5%) patients showed resolution in less than three days and the rest of the patients resolved hydrocephalus in a longer timeframe (more than three days). All patients lowered their Evans index compared to the index documented before radiosurgery, in a range from 0.02 to 0.17. Conclusion Radiosurgery is a non-invasive alternative treatment for primary and secondary brain tumors that debut with obstructive hydrocephalus, tumors expected to have a high alpha/beta ratio might be suitable to attempt radiosurgery to avoid permanently implanted devices such as VP shunts or other invasive procedures such as a third ventriculostomy. The present study demonstrated that in selected cases SRS can lead to hydrocephalus symptom resolution along with a decrease in ventricular size in a relatively short time frame. Little evidence exists regarding the effect of SRS on symptomatic hydrocephalus resolution and further histology-specific studies are required. We acknowledge that this approach requires immediate access to radiosurgery and close clinical follow-up to ensure success.

Radiomodulation in Mixed, Complex Cancer Pain by Triple Target Irradiation in the Brain: A Preliminary Experience.

Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication.

Visual Symptoms Outcomes in Cavernous Sinus Radiosurgery and a Systematic Review.

Introduction The complex anatomy of the cavernous sinus confers a true challenge when it comes to safe tumor resection. Due to its non-invasive nature, stereotactic radiosurgery (SRS) is expected to have lower mortality and morbidity rates than microsurgery. The purpose of this study was to evaluate clinical results regarding visual symptoms after SRS for benign tumors invading the cavernous sinus. We also conducted a systematic literature review to provide a robust analysis regarding visual outcomes. Methods The study included 58 patients (43 women and 15 men; mean age: 52 years) with benign tumors invading the cavernous sinus (27 pituitary adenomas and 31 meningiomas) who underwent SRS with different platforms between August 2011 and December 2021. Of these, 26 patients underwent surgery before SRS, and the remaining 32 had SRS as first-line therapy. We identified symptoms involving cranial nerves (CN) II, III, IV, and VI in 38 patients at the time of SRS. We conducted a systematic review to identify all original studies assessing visual outcomes. We searched PubMed, the Latin American and Caribbean Health Sciences Literature index, and Google Scholar using the Medical Subject Heading search terms "radiosurgery" and "cavernous sinus" for valid studies published until January 31, 2022. Results Regarding pituitary adenomas, median tumor volume was 2.05 cc, 3.12 cc, and 2.39 cc for Gamma Knife (GK), CyberKnife (CK), and tomotherapy (Tomo), respectively. Median doses were 14 Gy for GK, 17 Gy for CK, and 15 Gy for Tomo. For meningiomas, median tumor volume was 10.2 cc, 2.62 cc, and 16.3 cc for GK, CK, and Tomo, respectively. The median dose was 14 Gy for GK, 14 Gy for CK, and 14.5 Gy for Tomo. The overall tumor control rate was 100% with a median follow-up of 33 months (range: 6-128 months). A reduction of >30% in total tumor size per the Response Evaluation Criteria in Solid Tumors (RECIST) classification was documented in seven patients (RECIST II; 12.1%), 51 patients (87.9%) had stable disease (RECIST III), and no increase in tumor volume was documented in any patient. Visual symptoms improved in 51.7% of patients. In the systematic review, the mean visual improvement was 36% (range: 25.8-42.5%). Conclusion SRS is an effective treatment for benign tumors invading the cavernous sinus. In this series, patients who underwent SRS as a primary treatment showed improvement in pre-existing cranial neuropathy and visual symptoms. Given the natural history of these tumors, which tend to grow and cause visual alternations, treating asymptomatic patients is a feasible approach worth considering for the appropriate patients.

Radioneuromodulation by Dual-Target Irradiation in Pain Crisis From Trigeminal Neuralgia.

Background Radioneuromodulation (RNM) can explain the immediate pain relief experienced by a subgroup of patients after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). In this study, our main objective was to demonstrate that a minimum of a 50% reduction in TN pain can be achieved consistently in under 72 hours by targeting the affected nerve, the contralateral centromedian nucleus, and parafascicular complex in patients experimenting a prolonged refractory pain crisis. Methodology We treated eight patients experiencing severe TN pain crisis in whom percutaneous procedures had failed or were unwanted with SRS with an intention to procure pain relief in under 72 hours. The affected trigeminal nerve was targeted using a 4-mm collimator with an 80 to 90-Gy dose; an additional target was defined in the mesial portions of the thalamus and irradiated using the 4-mm collimator with a 120 to 140-Gy dose. Results The median duration of TN was 60 months, the median duration of pain crisis was 10.7 weeks despite the best medical treatment, and the mean presenting visual analogue score (VAS) was 10 at the time of treatment. The median follow-up was 135 days (range, 65-210). Twenty-four hours after treatment, two (25%) patients had no pain (VAS 0), three (37.5%) had mild pain (VAS 1 to 3), and three (37.5%) had moderate pain (VAS 4 to 7). Forty-eight hours after treatment, all patients reported pain relief, seven (87.5%) reported >50%, and one (12.5%) patients reported 30% relief. The three-month median VAS score was 3 (range, 0 to 5). At the last follow-up, there were no adverse events to report. Conclusions Dual irradiation to the affected trigeminal nerve and contralateral mesial structures of the thalamus may provide fast pain relief for patients experiencing a prolonged pain crisis from TN, which veers away from the concept that the SRS pain relief effect is generally delayed and holds no place in the management of such patients. Although this is a small series with a limited follow-up duration, no adverse effects were noted. RNM can be defined as the capacity to alter neuronal activity through targeted delivery of a stimulus of radiation at a duration too brief to be explained by the development of a focal lesion. The immediate pain relief and its habitual oscillatory nature of lesser pain recurrence in most patients until enough time elapses for pain stabilization clinically demonstrates that the pain circuitry is altered and remains functional, thus accomplishing a neuromodulation effect even at the face of an apparent doses suspected to be ablative. Further research is needed to understand if this clinical effect is achieved with a suspected sub-ablative dose.

Stereotactic Radiosurgery for Recurrent Glioblastoma Multiforme: A Retrospective Multi-Institutional Experience.

Introduction Glioblastoma multiforme (GBM) is the most common and lethal primary malignancy of the central nervous system. Despite standard therapy protocols, such as aggressive surgical resection, radiotherapy, and chemotherapy, GBM's aggressive nature produces low survival rates. Tumor recurrence and progression are nearly universal. Stereotactic radiosurgery (SRS) has been studied as an alternative treatment for recurrent GBM as a minimally invasive option that might prolong survival. The objective of this retrospective study was to evaluate the efficacy of SRS as a treatment modality considering overall survival (OS) in patients with GBM who had tumor recurrence and were treated with SRS in three different institutions. Materials and methods We retrospectively reviewed patients who received SRS for recurrent GBM between 1992 and 2020. A total of 46 patients were included in this study. We recorded age at diagnosis, the extent of surgical resection, radiation treatment, chemotherapy regimen, Karnofsky Performance Status at the time of SRS and at last follow-up, use of adjuvant chemotherapy after SRS, and response evaluation criteria in solid tumors. Primary endpoints were OS after initial diagnosis and OS from the date of the SRS procedure. Results Patients received SRS at a median of 10 months (range, 1 to 94 months) after their initial diagnoses. Median follow-up was seven months from the time of SRS and 22.8 months since diagnosis. The estimated median OS for all patients was nine months (range, 1 to 42 months) after SRS and 23.8 months (range, 4 to 102 months) after diagnosis. Median OS after SRS was seven months for patients treated from 1992 to 2011 and nine months for those treated from 2012 to 2020 (p = 0.008; X2 = 7.008). Median OS for younger patients (i.e., those aged <50 years) was 37.1 months compared to 18.6 months for older patients (i.e., those aged >50 years; p = 0.04; X2 = 3.870). Patients who received SRS after 10 months since diagnosis had a median OS of 36.2 months versus those who received SRS sooner than 10 months, who had an OS of 15 months (p = 0.004; X2 = 8.145). Radiosurgery doses larger than 15 Gy correlated with a median survival of nine months versus seven months in those treated with doses <15 Gy (p = 0.01; X2 = 6.756). Lastly, patients who received adjuvant bevacizumab (BEV) and or chemotherapy after SRS had a median survival of 12 months versus seven months for patients who did not receive any additional therapy after SRS (p = 0.04; X2 = 4.196). Conclusion SRS focal recurrent GBM in selected patients may improve OS, especially when combined with adjuvant therapy such as BEV and chemotherapy. Other prognostic variables proved relevant such as patients' age, the dose delivered, and surgery-to-SRS time that translates to the time of recurrence. Our results were consistent with the published literature and added to the accumulating evidence regarding SRS in recurrent GBM; however, extensive, multi-center studies are required to make definitive recommendations on this treatment approach.

Gamma Ray Radiosurgery for Trigeminal Neuralgia: Targeting Proximal or Distal to the Dorsal Root Entry Zone.

Introduction Stereotactic radiosurgery for trigeminal neuralgia (TN) has gained interest among patients who are not suitable for surgical procedures. Although two target zones are more recognized - dorsal root entry zone (DREZ) and retrogasserian zone (RGZ) - the optimal targeting technique remains controversial in terms of clinical outcomes and rates of complications. Therefore, various modifications to the radiosurgical technique for TN have been made. Objective This study aimed to determine the differences in shoot location (i.e., RGZ vs. DREZ) regarding effectiveness and adverse effects in patients with medically refractory TN. Additionally, we evaluated the effect of the integral dose (ID) on treatment outcomes and complications. Methods We present a retrospective cohort study of 49 patients with primary, drug-resistant TN treated with gamma knife radiosurgery targeting the distal and proximal parts of the nerve regarding the DREZ with a prescription dose of 90 Gy (80 to 96 Gy). A subset of these patients (n=38) where the ID could be measured to the nerve was correlated to treatment outcomes and complications. Results The median follow-up time was 36 months for RGZ and 51 months for DREZ targets. Neurovascular conflict was identified in 87.5% of the RGZ group and 88.2% of the DREZ group. Using the Barrow Neurological Institute (BNI) pain score, 26 (81.3%) RGZ and 12 (70.6%) DREZ patients were successfully treated (BNI I-IIIb; p=0.02). Seven (21.9%) RGZ and eight (47.1%) DREZ patients reported complete pain relief without medication (BNI I). Time response was 22.3 days for RGZ and 34.1 days for DREZ (p=0.277). There were 10 (31.3%) patients in the RGZ group with associated complications versus six (35.3%) patients in the DREZ group (χ2=0.0826, degree of freedom=1, p=0.773). Treatment outcomes using higher ID were better in the RGZ than DREZ (81.8% vs. 57.1, respectively), and a significant association was found between a higher ID delivered to the nerve and the development of complications (p=0.02). Conclusion Based on the obtained results, the RGZ was a more effective targeting area with better treatment outcomes without significant differences in complication rates than DREZ. A higher ID at the RGZ than DREZ had a greater therapeutical effect. Further investigation regarding the optimal target area along the ID delivered and clinical outcomes are required.

Multiplatform Radiosurgery for Intracranial Meningiomas and Dose to the Dural Tail.

Introduction Meningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail. Methods From February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Development Co., Shenzhen, China]), TomoTherapy® (Tomo [Accuray Inc., Sunnyvale, CA]), and CyberKnife® (CK [Accuray Inc.]). All plans were retrospectively reviewed to establish the maximum distance (MaxDis) from the prescription dose to the end of the dural tail and the minimum dose at the dural tail (MinDoseT) at this point. We also established the midpoint distance (MPDis) from the prescription dose to MaxDis and the dose at this point (MPDose). Plans were further distinguished when the physician intended to cover the dural tail versus when not. Patients and tumor response were assessed by imaging and clinical and phone call evaluations. Results Of the 143 patients, 81 were treated using Gamma, 34 using Tomo, and 28 using CK. Eighty patients were eligible for follow-up, of whom 58 (72.5%) had an unmistakable dural tail sign. Median follow-up was 1,118 days (range 189-3,496), mean age was 54.5 (range 19-90), and 61 were women, and 19 were men. Overall tumor volume was 6.5 cc (range 0.2-59); mean tumor volumes by different platforms were 2.4, 9.45, and 8 cc; dose prescribed and mean tumor coverage were 14 Gy and 92%, 14.5 Gy and 95%, and 14 Gy and 95.75% with Gamma, Tomo, and CK, respectively. The dural tail was drawn and planned with an attempt to treat in 18 patients (31%); the mean MaxDis, MinDoseT, MPDis, and MPDose were 9.0 mm, 2 Gy, 4.5 mm, and 10.6 Gy, respectively. At last follow-up, tumor control was achieved in 96% of patients for the whole series, and there were no statistical variations regarding tumor volume, dose, conformality, or control when stereotactic radiosurgery was used to cover the dural tail versus when it was not (p=0.105). One patient experienced a Grade 4 Radiation Therapy Oncology Group toxicity as an adverse radiation effect that required surgery, and 11 (7.6%) experienced a Grade 1 toxicity. Conclusions This is our preliminary report regarding the efficacy of radiosurgery for meningiomas using diverse platforms at three years of follow-up; the results regarding tumor control are in accordance with the published literature as of this writing. A conscious pursuit of the dural tail with the prescription dose has not proven to provide better tumor control than not doing so - even small areas of the tumor uncovered by the prescription dose did not alter tumor control at current follow-up. The doses delivered to these uncovered areas are quite significant; further follow-up is necessary to validate these findings.

Electroconvulsoterapia en el primer episodio de esquizofrenia: impacto en la evolución / Electroconvulsoterapia in the first episode of schizophrenia: impact on evolution

La esquizofrenia es una patología que evolucionade forma crónica, proclive al deterioro, siendo este último variable de acuerdo con comorbilidades presentes y adherencia al tratamiento integral. Genera alteraciones cognitivas e influye negativamente en el desempeño de quienes la padecen, causando detrimento global de los pragmatismos. La electroconvulsoterapia es una opción terapéutica ampliamente utilizada en nuestro país para tratar sintomatología del humor y episodios psicóticos agudos, entre otros. En la actualidad se sabe que la detección e intervención precoz de un episodio psicótico agudo —el cual puede corresponder al primer episodio psicótico de esquizofrenia —mejora el pronóstico a largo plazo. El objetivo es demostrar si existe un vínculo entre la indicación de electroconvulsoterapia durante el primer episodio psicótico de esquizofrenia y la duración del intervalo libre de internación. Este es un estudio de tipo analítico, observacional, retrospectivo (cohorte histórica) que busca aumentar las evidencias en este amplio campo de investigación. Observamos que el tiempo libre de internación luego de la primera hospitalización no tuvo relación con el hecho de si recibieron electroconvulsoterapia o no; sin embargo, al realizar el análisis de potencia estadístico surge que los resultados no son concluyentes. Se destaca el importante porcentaje de patología dual en este grupo de usuarios: un 39%.

Schizophrenia is a chronic disease, prone todeterioration, the latter being variable accordingto comorbidities and treatment adherence. It generates cognitive impairment and adverselyaffects overall performance, causing deterioration of pragmatisms. Electroconvulsive therapy is awidely used therapeutic option in our countryfor acute affective and psychotic episodes. It iswell known that early detection and interventionof an acute psychotic episode —which maycorrespond to the first psychotic episode of schizophrenia— improves long-term prognosis.This study intended to show whether there is alink between early indication of electroconvulsive therapy during the first episode and timeto relapse and hospital readmission. This is ananalytical, observational, retrospective (historical cohort) study, which aims to increase theevidence in this broad research field. As a resultthere was no link between time to relapse and electro convulsive therapy in the first episode; nevertheless after a post hoc analysis resultsare not conclusive. Dual diagnosis stands outin this group and corresponds to 39%.