Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

OBJECTIVE: Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS: There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS: SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review.

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications.

Upfront stereotactic radiosurgery versus adjuvant radiosurgery for parasagittal and parafalcine meningiomas: a systematic review and meta-analysis.

Parafalcine and parasagittal (PFPS) are common locations for meningiomas. Surgical resection for these tumors, the first-line treatment, poses challenges due to their proximity to critical structures. This systematic review investigates the use of stereotactic radiosurgery (SRS) as a treatment for PFPS meningiomas, aiming to elucidate its safety and efficacy. The review adhered to PRISMA guidelines. Searches were conducted on MEDLINE, Embase, and Cochrane. Inclusion criteria involved studies on SRS for PFPS meningiomas, reporting procedure outcomes and complications. Tumors were presumed or confirmed to be WHO grade 1. Data was systematically extracted. Meta-analysis was performed where applicable. The review included data from eight studies, 821 patients with 878 lesions. Tumor control was achieved in greater than 80% of cases. Adverse radiation effects were reported in 7.3% of them. Recurrence and further surgical approach were observed in 17.1% and 9.2% of cases, respectively. Symptom improvement was noted in 33.2% of patients. Edema occurred in approximately 25.1% of patients. A subgroup of 283 patients had upfront SRS, achieving tumor control in approximately 97% of such cases. SRS is a safe and effective treatment for PFPS meningiomas, both as an adjuvant therapy and as an upfront treatment for often smaller tumors. Post-SRS edema can typically be managed medically and usually does not require further surgical intervention. Further studies should provide more specific data on PFPS meningiomas. The use of single and hypofractionated SRS for larger volume PFPS meningiomas should be more explored to better define the risks and benefits.

Retrograde thoracic spinal cord stimulation paddle placement for complex persistent spinal pain syndrome type 2.

BACKGROUND: Spinal cord stimulation (SCS) is a cost-effective option for treating refractory persistent spinal pain syndrome type-2 (PSPS-2). For patients with extensive spine instrumentation including the thoraco-lumbar junction, percutaneous placement of SCS leads is usually not an option being paddle leads typically implanted anterograde. Paddle lead placement will be particularly challenging in more complex cases when the instrumentation covers the targeted level. To overcome this barrier, we studied using a retrograde approach to reach the sweet spot, facilitate the placement, and reduce associated risks. OBJECTIVES: To study the use of retrograde SCS paddle as a placement method to optimize the spinal cord target and reduce the risks of conventional placement in complex cases. STUDY DESIGN: Case series and technical note. METHODS: We present three cases of thoracic retrograde SCS paddle lead placement cases, detailing patient selection, operative technique, and outcome. All the cases had extensive instrumentation to the thoraco-lumbar spine, and one had additional spinal canal stenosis. The surgical procedure entailed a retrograde midthoracic inter-laminar approach, flavectomy, and caudal placement of the paddle lead with intraoperative neurophysiologic monitoring (IONM) guidance for functional midline determination. RESULTS: All the cases had a successful lead placement over the sweet spot without complications. The same approach was used to decompress a focal spinal stenosis in one case. One case had significantly improved pain and hence underwent a pulse generator implant. The other cases had non-satisfactory pain control and were explanted. LIMITATIONS: These case description could guide technical procedural steps, however, a larger number of such cases would be needed to describe further technical nuances. CONCLUSIONS: We demonstrated that placing SCS paddle leads via retrograde midthoracic approach with IONM guidance is safe. This procedure should be an option for SCS paddle implants in patients with posterior spinal fusion encompassing the intended targeted spinal stimulation level.

Fitness-to-drive after adult civilian traumatic brain injury: protocol for a systematic review and meta-analysis.

Traumatic brain injury (TBI) poses significant challenges for assessing fitness-to-drive (FTD) and determining the appropriate timing for return-to-driving (RTD) in civilian adults. This systematic review and meta-analysis protocol is designed to offer a comprehensive assessment of RTD timelines post-TBI, examining the effects of injury severity as well as demographic and clinical factors that influence driving capabilities. In response to gaps identified in previous literature-namely, the absence of recent systematic search strategies and thorough quality assessments-this study employs rigorous methodologies for literature search, data extraction, and evaluation of study quality. Our approach aims to provide reliable estimates and detailed analyses of subgroups within the TBI population. The findings aim to support clinical decision-making, inform RTD readiness, and potentially impact policy and driving assessment protocols. Ultimately, this review seeks to contribute to public safety measures, reduce traffic-related harm, and improve life outcomes for individuals recovering from TBI, thereby filling a vital research niche in neurotrauma rehabilitation.

Stereotactic radiosurgery for non-functioning pituitary tumor: a multicenter study of new pituitary hormone deficiency.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS: Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS: 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR):18.9]) were treated using a median margin dose of 14Gy (IQR:4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio HR:0.33 [95%CI:0.18-0.60], p<0.001).The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI:11-19.4) at 5 and 10 years, respectively.A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR:3.47, 95% CI:1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph and growth hormone deficiency was 8% (95% CI:3.9-11.9), 8.3% (95% CI:3.9-12.5), 3.5% (95% CI:1.7-5.2), and 4.7% (95% CI:1.9-7.4), respectively at 10 years. CONCLUSION: SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

Robotic-Assisted Stereoelectroencephalography: A Systematic Review and Meta-Analysis of Safety, Outcomes, and Precision in Refractory Epilepsy Patients.

Robotic assistance in stereoelectroencephalography (SEEG) holds promising potential for enhancing accuracy, efficiency, and safety during electrode placement and surgical procedures. This systematic review and meta-analysis, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration, delves into the latest advancements and implications of robotic systems in SEEG, while meticulously evaluating outcomes and safety measures. Among 855 patients suffering from medication-refractory epilepsy who underwent SEEG in 29 studies, averaging 24.6 years in age, the most prevalent robots employed were robotic surgical assistant (ROSA) (450 patients), Neuromate (207), Sinovation (140), and ISys1 (58). A total of 8,184 electrodes were successfully implanted, with an average operative time of 157.2 minutes per procedure and 15.1 minutes per electrode, resulting in an overall mean operative time of 157.7 minutes across all studies. Notably, the mean target point error (TPE) stood at 2.13 mm, the mean entry point error (EPE) at 1.48 mm, and postoperative complications occurred in 7.69% of robotically assisted (RA) SEEG cases (60), with 85% of these complications being asymptomatic. This comprehensive analysis underscores the safety and efficacy of RA-SEEG in patients with medication-refractory epilepsy, characterized by low complication rates, reduced operative time, and precise electrode placement, supporting its widespread adoption in clinical practice, with no discernible differences noted among the various robotic systems.

Exploring the Neuroprotective Effects of Spirulina platensis: Insights Into Hemorrhagic Volume and Histological Outcomes.

Background Hemorrhagic events can result in significant neurological damage, and identifying effective strategies for neuroprotection is crucial. Several studies have directed their attention to the alterations in perilesional parenchymal tissue. These investigations have sought to modify ischemic and metabolic changes by utilizing potential neuroprotective agents and to develop strategies that effectively mitigate secondary perilesional neuronal damage. By gaining a deeper understanding of its mechanisms and efficacy, Spirulina platensis can emerge as a promising therapeutic intervention for various neurological disorders. Methodology This controlled and blinded experimental study was conducted on adult male Wistar rats. The rats were divided into the treatment group, which received Spirulina platensis extract for 30 days before the hemorrhagic event, and the control group, where all animals underwent the same experimental hemorrhage model using collagenase. Each group was divided into the following three subgroups based on the sacrifice time: six hours, 24 hours, and 30 days. The brain section with the largest hemorrhage volume was selected for histological analysis. The number of viable neurons was analyzed in the perilesional zone and the cortical fields along the puncture trajectory. Neurofunctional evaluations were conducted on animals sacrificed 15 and 30 days after the procedure. Results Initial analysis showed no significant difference in viable neurons between groups (p = 0.63). Still, after 24 hours, the treatment group had a significantly higher number of viable neurons per peripheral fields (18.5) compared to the control group (13.4; p < 0.05). Neurofunctional tests at 15 days indicated a trend toward significance in absolute discrimination (p = 0.054), with the control group showing higher mean values (5.5, SD = 3.1) than the treatment group (-1, SD = 5.1). The discrimination index exhibited a significant difference (p < 0.01), with higher mean values in the control group (0.59, SD = 0.34) compared to the treatment group (-0.05, SD = 0.21). No significant differences were found in other neurofunctional parameters at this time point. At 30 days, no significant differences were observed in absolute discrimination, discrimination index, contralateral paw elevation, rearing time, and wire hanging time test (p > 0.1); however, the treatment group presented a better motor performance in the open field test (14.2, SD = 9.02) compared to the control group (5.25, SD = 2.06), approaching significance (p = 0.06). Conclusions The group treated with Spirulina platensis demonstrated significantly more viable neurons in the perilesional fields 24 hours after the induced hemorrhage. The treatment group also had a relatively better motor performance in the open field test 30 days after the hemorrhage (p = 0.06). These findings suggest a potential neuroprotection effect and warrant further investigations to explore the effects of Spirulina platensis and its active component phycocyanin in acute neurological conditions.

Unusual Intraventricular Bullet Migration During Operation: A Case Report on Treatment Strategies.

Gunshot head injuries are increasingly prevalent in the urban setting and carry complex technical and clinical decision-making challenges to practicing neurosurgeons. Here, we present a unique case of a patient who suffered a gunshot injury and presented to the emergency department with an intraventricular bullet lodgment without significant neurological deficits. The patient was rushed to the operating room to remove the bullet after neuroimaging demonstrated its migration inside the ventricular system. The patient showed a favorable outcome postoperatively. This case report highlights the importance of prompt diagnosis and tailored management strategies in cases of intraventricular bullet lodgment.

As artérias lenticuloestriadas podem interferir na extensão da ressecção tumoral e sobrevida nos gliomas da ínsula? / Can lenticulostriated arteries interfere with the extent of tumor resection and survival in insula gliomas?

Introdução: Os gliomas são tumores encefálicos e da medula espinhal que se originam nas células gliais e cuja progressão invade o tecido cerebral adjacentee e dentre eles um dos mais desafiadores são localizados no lobo cerebral da ínsula. Estas artérias irrigam estruturas nobres e sua lesão pode produzir danos sensitivos, motores e de linguagem. Objetivo: Descrever o impacto da extensão da ressecção, sobrevida global e dos resultados funcionais após a cirurgia dos gliomas insulares, quando estes tumores estejam ou não envolvidos pelas artérias lenticuloestriadas. Métodos: Revisão integrativa nas plataformas virtuais em português e inglês, buscando AND ou OR dados através dos seguintes descritores "Gliomas da ínsula, Mapeamento cerebral, Artérias lenticuloestriadas". A busca inicial foi baseada no título e/ou resumo. Decididos os trabalhos incluíveis foi realizada a leitura na íntegra dos textos. Ao total foram estudados 55 artigos. Resultados: O lobo da ínsula fica "escondido" pela sobreposição dos lobos frontal, parietal e temporal. Para alcançá-lo pode-se realizar as abordagens transsilviana ou transcortical. Ocorre que ao chegar na ínsula visualiza-se significativa ramificação constituída pelas artérias lenticuloestriadas, cuja manipulação pode determinar déficit neurológico e, ao se aprofundar no córtex insular, depara-se com outras estruturas tão importantes quanto a própria ínsula. O conhecimento anatômico das artérias lenticuloestriadas e suas relações é de fundamental importância para a ressecção de glioma insular, pois o comprometimento delas e da artéria cerebral média podem determinar a isquemia dos núcleos da base e da cápsula interna. Conclusão: O tratamento dos gliomas insulares permanece como grande desafio. Devido à sua localização e possibilidade de desenvolvimento de déficits neurológicos na manipulação cirúrgica é necessário não somente conhecer sua localização topográfica, mas também a íntima relação vascular com as artérias lenticuloestriadas. O envolvimento delas pelo tumor possui implicações na sobrevida e na preservação da função neurológica. O conhecimento detalhado da anatomia da região é fundamental para diminuir complicações que afetem grandemente a qualidade de vida dos pacientes.

Introduction: Gliomas are brain and spinal cord tumors that originate in glial cells and whose progression invades the adjacent brain tissue and among them one of the most challenging are located in the cerebral lobe of the insula. These arteries supply noble structures and their damage can cause sensory, motor and language damage. Objective: To describe the impact of the extent of resection, overall survival and functional results after surgery for insular gliomas, when these tumors are or are not involved by lenticulostriate arteries. Methods: Integrative review on virtual platforms in Portuguese and English, searching for AND or OR data using the following descriptors "Insula gliomas, Brain mapping, Lenticulostriate arteries". The initial search was based on the title and/or abstract. Once the included works were decided, the texts were read in full. In total, 55 articles were studied. Results: The insula lobe is "hidden" by the overlap of the frontal, parietal and temporal lobes. To achieve this, transsylvian or transcortical approaches can be performed. It turns out that when arriving at the insula, a significant branch made up of lenticulostriate arteries is seen, the manipulation of which can cause neurological deficits and, when going deeper into the insular cortex, one comes across other structures as important as the insula itself. Anatomical knowledge of the lenticulostriate arteries and their relationships is of fundamental importance for the resection of insular glioma, as their involvement and that of the middle cerebral artery can determine ischemia of the basal ganglia and internal capsule. Conclusion: The treatment of insular gliomas remains a major challenge. Due to its location and the possibility of developing neurological deficits during surgical manipulation, it is necessary not only to know its topographic location, but also the intimate vascular relationship with the lenticulostriate arteries. Their involvement by the tumor has implications for survival and preservation of neurological function. Detailed knowledge of the region's anatomy is essential to reduce complications that greatly affect patients' quality of life.

É possível prever a mortalidade molecular em meduloblastomas pela análise dos receptores de membrana CD114? / Is it possible to predict molecular mortality in meduloblastomas by analysis of CD114 membrane receptors?

Introdução: Os meduloblastomas são os tumores sólidos mais comuns da infância e classificados em 4 subgrupos moleculares: WNT, SHH, grupo 3 e grupo 4. Muitos estudos buscam desenvolvimento de novos quimioterápicos para os meduloblastomas através da identificação de genes cuja expressão sejam novos alvos moleculares para drogas, como receptores de membrana associados a replicação celular. Objetivo: Avaliar a associação da expressão de CD114 com a mortalidade de pacientes portadores de meduloblastoma. Métodos: Revisão feita colhendo informações publicadas em plataformas virtuais em português e inglês. Inicialmente foi realizada busca por descritores relacionados ao tema - neurocirurgia, oncologia cirúrgica, terapia de alvo molecular e meduloblastoma - e seus equivalentes em inglês - neurosurgery, surgical oncology, molecular targeted therapy e medulloblastoma - com busca AND ou OR, considerando o título e/ou resumo. Após, foram incluídos somente os que tinham maior relação ao tema, e realizada a leitura da íntegra dos textos. Finalmente foram referidos 2 artigos. Resultados: Há diferença na expressão do receptor de membrana CD114 entre o Grupo 3 e os demais grupos moleculares, além de diferença entre o subtipo molecular SHH γ e os subtipos moleculares Grupo 3 α e Grupo 3 ß. Não houve diferença estatisticamente significativa entre os demais grupos e subtipos. Em relação à mortalidade, esta revisão não demonstrou significância estatística na relação entre expressões baixas e elevadas desse gene e a mortalidade. Conclusão: Não há relação direta entre a expressão do receptor de membrana CD114 e a mortalidade em pacientes portadores de meduloblastoma. Entretanto, são necessários estudos adicionais sobre as vias de sinalização intracelulares associadas a esse receptor e ao seu gene, o CSF3R.

Introduction: Medulloblastomas are the most common solid tumors of childhood and classified into 4 molecular subgroups: WNT, SHH, Group 3 and Group 4. Many studies seek to develop new chemotherapy drugs for medulloblastomas by identifying genes whose expression is new molecular targets for drugs, such as membrane receptors associated with cell replication. Objective: To evaluate the association of CD114 expression with mortality in patients with medulloblastoma. Methods: Review carried out collecting information published on virtual platforms in Portuguese and English. Initially, a search was carried out for descriptors related to the topic - neurosurgery, surgical oncology, molecular targeted therapy and medulloblastoma, with AND or OR search, considering the title and/or summary. Afterwards, only those that were most related to the topic were included, and the texts read in full. Finally, 23 articles were referred. Results: There is a difference in the expression of the CD114 membrane receptor between Group 3 and the other molecular groups, in addition to a difference between the SHH γ molecular subtype and the Group 3 α and Group 3 ß molecular subtypes. There was no statistically significant difference between the other groups and subtypes. Regarding mortality, this review did not demonstrate statistical significance in the relationship between low and high expressions of this gene and mortality. Conclusion: There is no direct relationship between the expression of the CD114 membrane receptor and mortality in patients with medulloblastoma. However, additional studies are needed on the intracellular signaling pathways associated with this receptor and its gene, CSF3R.

Memantine associated with ventricular-subcutaneous shunt promotes behavioral improvement, reduces reactive astrogliosis and cell death in juvenile hydrocephalic rats.

Hydrocephalus is defined as the accumulation of cerebrospinal fluid in the brain ventricles. The usual treatment of hydrocephalus is surgical (shunt), but not all patients can undergo treatment immediately after diagnosis. Thus, neuroprotective measures were tested to minimize the tissue damage involved. Memantine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, which has shown a neuroprotective action in neurodegenerative diseases. This study aimed to evaluate the neuroprotective response of memantine in animals treated with or without a ventricular-subcutaneous shunt. Seven-day-old male Wistar rats induced by intracisternal injection of kaolin were used, divided into five groups: intact control (n = 10), hydrocephalic (n = 10), hydrocephalic treated with memantine (20 mg/kg/day) (n = 10), hydrocephalic treated with shunt (n = 10), hydrocephalic treated with shunt and memantine (20 mg/kg/day) (n = 10). Memantine administration was started on the day after hydrocephalus induction and continued until the last day of the experimental period, totaling 21 consecutive days of drug application. The CSF shunt surgery was performed seven days after hydrocephalus induction. Behavioral tests (open field, and modified Morris water maze), histological, and immunohistochemical evaluations were performed. Treatment with memantine resulted in significant improvement (p < 0.05) in sensorimotor development, preservation of spatial memory, reduction of astrocytic reaction in the corpus callosum, cortex, and germinal matrix. When associated with the shunt, it has also been shown to reduce the cell death cascade. It is concluded that memantine is a promising adjuvant drug with beneficial potential for the treatment of lesions secondary to hydrocephalus.

Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial.

BACKGROUND: Adductor spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. The current standard of care is repeated botulinum toxin injections to weaken the adductor muscles. We sought to ameliorate the underlying neurological cause of SD with a novel therapy-deep brain stimulation (DBS). OBJECTIVE: To assess the safety of DBS in SD through phase I trial, and to quantify the magnitude of any benefit. METHODS: Six patients had left ventral intermediate nucleus (Vim) thalamic DBS and were randomized to 3 mo blinded-DBS "on" or "off" followed by a crossover. Primary outcomes were quality of life and quality of voice during the blinded phase. Patients continued with open-DBS "on." Secondary outcomes were comparisons of pre- and 1-yr cognitive, mood, and quality of life. This trial was registered with ClinicalTrials.gov (NCT02558634). RESULTS: There were no complications. Every patient reported an improvement in quality of life (P = .07) and had an improvement in quality of their voice (P = .06) when their blinded DBS was "on" versus "off." The trend did not reach statistical significance with the small sample size. Secondary outcomes showed no difference in cognition, an improvement in mood, and quality of life at 1 yr. CONCLUSION: This phase I randomized controlled trial confirmed that DBS can be performed safely in patients with SD. Blinded DBS produced a strong trend toward improved quality of life and objective quality of voice despite the small sample size. The cerebellar circuit, not the pallidal circuit, appears to be crucial for motor control of the vocal folds.

Intraperitoneal cannabidiol attenuates neonatal germinal matrix hemorrhage-induced neuroinflamation and perilesional apoptosis.

Background. As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the direct neuronal injury are still scarce. The present study aims to analyze the neuroprotective properties of cannabidiol in germinal matrix hemorrhage. Methods. 112 Wistar rat pups (P7) were submitted to an experimental collagenase induced model of GMH. Inflammatory response and neuronal death were analyzed both at the perilesional area as at the distant ipsilateral CA1 hippocampal area. Immunohistochemistry for GFAP and caspase 3 was used. The ipsilateral free water content was assessed for stimation of cerebral edema, and neurodevelopment and neurofunctional tests were conducted. Results. Reduction of reactive astrocytosis was observed both in the perilesional area 24 hours and 14 days after the hemorrhage lesion (p < 0.001) and in the Stratum oriens of the ipsilateral hippocampal CA1 14 days after the hemorrhage lesion (p < 0.05) in the treated groups. Similarly, there was a reduction in the number of Caspase 3-positive astrocytes in the perilesional area in the treated groups 24 hours after the hemorrhage lesion (p < 0.001). Finally, we found a significant increase in the weight of the rats treated with cannabidiol. Conclusion. The treatment of GMH with cannabidiol significantly reduced the number of apoptotic cells and reactive astrocytes in the perilesional area and the ipsilateral hippocampus. In addition, this response was sustained 14 days after the hemorrhage. These results corroborate our hypothesis that cannabidiol is a potential neuroprotective agent in the treatment of germinal matrix hemorrhage.

Epidemiological Profile of Intracerebral Hemorrhage during a 10-Year Period in a Southern Brazilian Region

Objective Spontaneous intracerebral hemorrhage is responsible for 20% of all cases of cerebrovascular accidents, which might lead to functional disabilities and death. There are few epidemiological data on spontaneous intracerebral hemorrhage in Brazil, and more specifically in the southern region of the country. Methods We reviewed data of 221 patients with intracerebral hemorrhage who attended our department between January of 2004 and December of 2013 and were registered as I61 and I62 according to the 10th edition of the International Classification of Diseases and Related Health Problems (ICD-10). Results From the 221 cases, 53.8% were male, and the median age was 63 years old. Arterial hypertension was reported in 62.4% of the patients. Surgical treatment was performed in 28.9% of all cases and pneumonia affected 19.9%. In 73.4% of the cases, the patients died or were severely disabled at discharge. We found an association of heart disease, coagulopathies, chronic kidney disease, anticoagulant drugs use, surgical treatment, and pneumonia with a poorer outcome. Conclusion The present study describes the epidemiological profile of intracerebral hemorrhage in a southern Brazilian population during a 10-year period.

Introdução A hemorragia cerebral espontânea é responsável por 20% de todos os acidentes vasculares cerebrais e acarreta grande número de óbitos e incapacidade funcional. Poucos são os dados epidemiológicos da hemorragia cerebral espontânea no Brasil, e especificamente no Sul do Brasil. Metodologia Foram revisados 221 casos de hemorragia cerebral espontânea atendidos entre janeiro de 2004 e dezembro de 2013, selecionados aleatoriamente dentre os casos registrados como I61 e I62 de acordo com a 10a revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID-10) nesse período. Resultados Dos 221 casos, 53,8% eram do sexo masculino. A idade média foi de 63 anos e a distância média do local de residência até o centro de tratamento foi de 78,7 Km. Hipertensão arterial sistêmica foi relatada em 62,4% dos casos, diabetes mellitus em 20,4% e tabagismo em 15,4%. Tratamento cirúrgico foi realizado em 28,9% dos casos; pneumonia ocorreu em 19,9%, e 73,4% evoluíram com óbito ou incapacidade grave. Encontramos uma associação entre cardiopatia, coagulopatias, insuficiência renal crônica, uso de anticoagulantes, tratamento cirúrgico, pneumonia e sepse com um pior desfecho. Conclusão O presente estudo descreve o perfil epidemiológico da hemorragia cerebral espontânea de uma população do Sul do Brasil e os fatores prognósticos encontrados no período de 10 anos.

Spinal Neurocysticercosis: A Rare Variant of a Common Parasitic Infection

Neurocysticercosis is the most common parasitic infection affecting the central nervous system, usually involving the brain parenchyma, intracranial subarachnoid space, or ventricular system. In rare cases, there is involvement of the spine (vertebral, epidural, subdural, arachnoid, or intramedullary). Even in endemic regions, this variant is rare, with an incidence below 5% of all patients. The diagnosis is made based on the symptoms, which can be very unspecific, imaging and CSF analysis, with biopsy as a possibility. Treatment is usually curative, but important deficits can develop, due to compression of the spinal cord or nerve roots, arachnoiditis, or meningitis. We present the case of a patient who developed this entity, with poor clinical scenario, and review the literature on the topic.

Neurocisticercose é a infecção parasitária mais comum afetando o sistema nervoso central, geralmente envolvendo o parênquima cerebral, espaço subaracnóide intracraniano ou sistema ventricular. Em raros casos, há envolvimento da coluna vertebral, espaços epidural e subdural, aracnoide, ou intramedular. Mesmo em áreas endêmicas, esta variante é rara, com incidência abaixo de 5% entre todos os pacientes. O diagnóstico é feito com base nos sintomas, que podem ser bastante inespecíficos, neuroimagem e análise do líquor, sendo a biópsia uma possibilidade. O tratamento geralmente é curativo, porém importantes déficits podem se desenvolver, devido à compressão da medula espinhal ou raízes nervosas, aracnoidite ou meningite. Relatamos o caso de um paciente que desenvolveu esta entidade, com sintomatologia escassa, e revisamos a literatura sobre este tópico.

Medullary Paracoccidioidomycosis Treated Successfully with Oral Itraconazole

Paracoccidioidomycosis is the most prevalent endemic mycosis in Latin America, with a great incidence in Brazil. Although a common disease, its medullary form is rare. We present a case report of medullary paracoccidioidomycosis presenting with subacute, progressive, spinal cord symptoms, and with multiple expansive lesions into the cervical and thoracic spinal cord. The patient was treated with itraconazole and showed good clinical and radiologic recovery upon six months of follow-up.

Paracoccidioidomicose é a micose endêmica de maior prevalência na America Latina, com grande incidência no Brasil. Apesar de comum, sua forma medular é rara. Apresentamos um relato de caso de paracoccidioidomicose medular apresentando sintomas subagudos e progressivos na medula, com múltiplas lesões expansivas na medula, cervical e torácica. O paciente foi tratado com itraconazole e apresentou melhora clínica e recuperação radiológica após seis meses.

The Corneomandibular Reflex and the race of the reflexes: Clinical and Historical Aspects

The corneomandibular reflex was first described in 1902 by German doctor Von Sölder, who reported the presence of the reflex in patients and in the general population. For him, the corneomandibular reflex represented an exaggeration of the normal response. This was one of the more than 250 reflexes described in the beginning of the 20th century, during the so called "race of the reflexes".

O reflexo córneo-mandibular foi descrito pela primeira vez em 1902 pelo alemão Von Sölder, que relatou a presença de reflexos em pacientes e indivíduos normais. Segundo ele, o reflexo córneo-mandibular representa um exagero da resposta convencional. Este é um dos mais de 250 reflexos descritos no início do século XX, durante a chamada "corrida dos reflexos".

Chiari IV Malformation, the Lückenschädel and Sagittal Craniosynostosis Association: Case Report and Literature Review / Associação entre malformação de Chiari IV, Lückenschädel e craniossinostose sagital: relato de caso e revisão de literatura

The association between Lückenschädel and craniosynostosis is unusual and unknown. Genetic origin is a possibility, representing one of many possible phenotypes for mutation. To the best of our knowledge, the association of such anomalies in a type IV Chiari malformation has never been reported before. The authors present the case of a patient with obstructive hydrocephalus, diagnosed with Chiari IV malformation associated with Lückenschädel and sagittal craniosynostosis. The Lückenschädel is the bone abnormality least commonly associated with Chiari malformation. It consists of a defect in the bones ofmembranous origin that formthe cranial vault. This anomaly arises from periosteal dysplasia, and is characterized by rounded and irregular gaps in the skull, bound by bony ridges. Craniosynostosis is due to premature fusion of the cranial sutures and is sometimes associated with the Chiari complex of malformations. The diagnostic of Lückenschädel and craniosynostosis is done by imaging, through which the skull assumes the aspect of a hive, characteristic of Lückenschädel and it is possible to see the premature fusion of the sutures. The Lückenschädel usually does not require treatment because of spontaneous resolution; whereas, craniosynostosis warrants surgery for aesthetic and functional reasons. The Chiari malformation IV only requires treatment when it results in syringomyelia or hydrocephalus.

O Lückenschädel e a craniossinostose são uma associação incomum e pouco conhecida, com possível origem genética, o que representa um dos muitos fenótipos possíveis para uma mutação. Até onde sabemos, a associação destas anomalias em um caso de malformação de Chiari tipo IV não foi relatada antes. Os autores apresentam o caso de um paciente com hidrocefalia obstrutiva, que foi diagnosticado com malformação de Chiari tipo IV associada com Lückenschädel e craniossinostose sagital. O Lückenschädel é a anormalidade óssea menos comum associada com a malformação de Chiari. É constituída por umdefeito nos ossos de origem membranosa que formam a abóbada craniana. Esta anomalia surge de displasia do periósteo e é caracterizada por falhas arredondadas e irregulares no crânio, delimitadas por cristas ósseas. A craniossinostose se deve à fusão prematura das suturas cranianas e é por vezes associada com o complexo de malformações de Chiari. Os diagnósticos de Lückenschädel e craniossinostose são feitos por imagem, onde o crânio assume um aspecto de colmeia, característico de Lückenschädel, e é possível ver a fusão prematura das suturas. O Lückenschädel geralmente não requer tratamento por causa de resolução espontânea e craniosynostosis necessita de cirurgia para fins estéticos e funcionais. A malformação de Chiari IV só requer tratamento quando resulta em siringomielia ou hidrocefalia.

Multiple Extracranial Metastases from a Rhabdoid Meningioma: A Case Report / Metástases Extracraniais Multiplas de um Meningioma Rabdóide: Relato de Caso

Meningiomas are among the most common intracranial primary tumors, and generally have a benign behavior. The incidence of extracranial metastasis of this pathology is low. There are different variants of them, with a wide variety of aggressiveness and potential tometastatic spread. Among themalignant meningiomas (1­3% of total), the rhabdoid variant is known for its aggressive biological and clinical behavior. It is also known that some histological subtypes are inherently prone to recur or spread, as the latter. In the latest World Health Organization classification, extracranial metastases are not currently considered a pathological criterion for malignancy, and, when present, they are most commonly found in the lung, liver, lymph nodes, and bone. Treatment is usually surgical resection of the metastases, but there is still no consensus about it. Owing to its poor prognosis, the rhabdoid subtype is commonly treated aggressively. Patients are submitted to local radiotherapy to prevent recurrence. Extracranial metastases of meningiomas are rare, but should always be remembered, especially in cases of local recurrence and malignant histology, as the rhabdoid variant. We report one case of extracranial metastases in a patient diagnosed with rhabdoid subtype of meningioma, and discuss the literature on this pathology.

Meningiomas estão entre os tumores intracranianos primários mais comuns, e geralmente possuem comportamento benigno. A incidência de metástases extracranianas desta patologia é baixa. Existem diversas variantes, com uma ampla variedade de agressividade e potencial para disseminação metastática. Entre os meningiomas malignos (1­3% do total), a variante rabdoide é conhecida por seu comportamento agressivo clínico e biológico. Também é sabido que alguns subtipos histológicos são propensos à recidiva e disseminação, como o supracitado. Na última classificação da Organização Mundial de Saúde, metástases extracranianas não são consideradas como critério patológico para malignidade, e, quando presentes, são geralmente encontradas nos pulmões, fígado, linfonodos e ossos. O tratamento é geralmente a ressecção cirúrgica das metástases, embora não há consenso. Devido ao seu prognóstico pobre, o subtipo rabdoide é comumente tratado de forma agressiva. Os pacientes são submetidos à radioterapia local para prevenção de recidivas. As metástases extracranianas de meningiomas são raras, mas sempre devem ser consideradas, especialmente em casos com recidiva local e histologia maligna, como a variante rabdoide. Relatamos um caso de metástases extracranianas em um paciente com o subtipo rabdoide de meningioma, e discutimos a literatura a seu respeito.