Clinical and Brain Morphometry Predictors of Deep Brain Stimulation Outcome in Parkinson's Disease.

Subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in advanced Parkinson's disease (PD) and to enable a reduction of anti-parkinsonian medication. While the levodopa challenge test and disease duration are considered good predictors of STN-DBS outcome, other clinical and neuroanatomical predictors are less established. This study aimed to evaluate, in addition to clinical predictors, the effect of patients' individual brain topography on DBS outcome. The medical records of 35 PD patients were used to analyze DBS outcomes measured with the following scales: Part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) off medication at baseline, and at 6-months during medication off and stimulation on, use of anti-parkinsonian medication (LED), Abnormal Involuntary Movement Scale (AIMS) and Non-Motor Symptoms Questionnaire (NMS-Quest). Furthermore, preoperative brain MRI images were utilized to analyze the brain morphology in relation to STN-DBS outcome. With STN-DBS, a 44% reduction in the UPDRS-III score and a 43% decrease in the LED were observed (p<0.001). Dyskinesia and non-motor symptoms decreased significantly [median reductions of 78,6% (IQR 45,5%) and 18,4% (IQR 32,2%) respectively, p=0.001 - 0.047]. Along with the levodopa challenge test, patients' age correlated with the observed DBS outcome measured as UPDRS-III improvement (ρ= -0.466 - -0.521, p<0.005). Patients with greater LED decline had lower grey matter volumes in left superior medial frontal gyrus, in supplementary motor area and cingulum bilaterally. Additionally, patients with greater UPDRS-III score improvement had lower grey matter volume in similar grey matter areas. These findings remained significant when adjusted for sex, age, baseline LED and UPDRS scores respectively and for total intracranial volume (p=0.0041- 0.001). However, only the LED decrease finding remained significant when the analyses were further controlled for stimulation amplitude. It appears that along with the clinical predictors of STN-DBS outcome, individual patient topographic differences may influence DBS outcome. Clinical Trial Registration Number: NCT06095245, registration date October 23, 2023, retrospectively registered.

Pretreatment with a dual antiplatelet and anticoagulant (APAC) reduces ischemia-reperfusion injury in a mouse model of temporary middle cerebral artery occlusion-implications for neurovascular procedures.

BACKGROUND: Several neurovascular procedures require temporary occlusion of cerebral arteries, leading to ischemia of unpredictable length, occasionally causing brain infarction. Experimental models of cerebral ischemia-reperfusion injury have established that platelet adhesion and coagulation play detrimental roles in reperfusion injury following transient cerebral ischemia. Therefore, in a model of cerebral ischemia-reperfusion injury (IRI), we investigated the therapeutic potential of a dual antiplatelet and anticoagulant (APAC) heparin proteoglycan mimetic which is able to bind to vascular injury sites. METHODS: Brain ischemia was induced in mice by transient occlusion of the right middle cerebral artery for 60 min. APAC, unfractionated heparin (UFH) (both at heparin equivalent doses of 0.5 mg/kg), or vehicle was intravenously administered 10 min before or 60 min after the start of ischemia. At 24 h later, mice were scored for their neurological and motor behavior, and brain damage was quantified. RESULTS: Both APAC and UFH administered before the onset of ischemia reduced brain injury. APAC and UFH pretreated mice had better neurological and motor functions (p < 0.05 and p < 0.01, respectively) and had significantly reduced cerebral infarct sizes (p < 0.01 and p < 0.001, respectively) at 24 h after transient occlusion compared with vehicle-treated mice. Importantly, no macroscopic bleeding complications were observed in either APAC- or UFH-treated animals. However, when APAC or UFH was administered 60 min after the start of ischemia, the therapeutic effect was lost, but without hemorrhaging either. CONCLUSIONS: Pretreatment with APAC or UFH was safe and effective in reducing brain injury in a model of cerebral ischemia induced by transient middle cerebral artery occlusion. Further studies on the use of APAC to limit ischemic injury during temporary occlusion in neurovascular procedures are indicated.

Flow diversion of ruptured intracranial aneurysms: a single-center study with a standardized antithrombotic treatment protocol.

BACKGROUND: The use of antithrombotic medication following acute flow diversion for a ruptured intracranial aneurysm (IA) is challenging with no current guidelines. We investigated the incidence of treatment-related complications and patient outcomes after flow diversion for a ruptured IA before and after the implementation of a standardized antithrombotic medication protocol. METHODS: We conducted a single-center retrospective study including consecutive patients treated for acutely ruptured IAs with flow diversion during 2015-2023. We divided the patients into two groups: those treated before the implementation of the protocol (pre-protocol) and those treated after the implementation of the protocol (post-protocol). The primary outcomes were hemorrhagic and ischemic complications. A secondary outcome was clinical outcome using the modified Ranking Scale (mRS). RESULTS: Totally 39 patients with 40 ruptured IAs were treated with flow diversion (69% pre-protocol, 31% post-protocol). The patient mean age was 55 years, 62% were female, 63% of aneurysms were in the posterior circulation, 92% of aneurysms were non-saccular, and 44% were in poor grade on admission. Treatment differences included the use of glycoprotein IIb/IIIa inhibitors (pre-group 48% vs. post-group 100%), and the use of early dual antiplatelets (pre-group 44% vs. 92% post-group). The incidence of ischemic complications was 37% and 42% and the incidence of hemorrhagic complications was 30% and 33% in the pre- and post-groups, respectively, with no between-group differences. There were three (11%) aneurysm re-ruptures in the pre-group and none in the post-group. There were no differences in mortality or mRS 0-2 between the groups at 6 months. CONCLUSION: We found no major differences in the incidence of ischemic or hemorrhagic complications after the implementation of a standardized antithrombotic protocol for acute flow diversion for ruptured IAs. There is an urgent need for more evidence-based guidelines to optimize antithrombotic treatment after flow diversion in the setting of subarachnoid hemorrhage.

Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial.

BACKGROUND: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). OBJECTIVE: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. METHODS: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18 F]FE-PE2I. RESULTS: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. CONCLUSIONS: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Preclinical evaluation of ADVM-062, a novel intravitreal gene therapy vector for the treatment of blue cone monochromacy.

Blue cone monochromacy (BCM) is a rare X-linked retinal disease characterized by the absence of L- and M-opsin in cone photoreceptors, considered a potential gene therapy candidate. However, most experimental ocular gene therapies utilize subretinal vector injection which would pose a risk to the fragile central retinal structure of BCM patients. Here we describe the use of ADVM-062, a vector optimized for cone-specific expression of human L-opsin and administered using a single intravitreal (IVT) injection. Pharmacological activity of ADVM-062 was established in gerbils, whose cone-rich retina naturally lacks L-opsin. A single IVT administration dose of ADVM-062 effectively transduced gerbil cone photoreceptors and produced a de novo response to long-wavelength stimuli. To identify potential first-in-human doses we evaluated ADVM-062 in non-human primates. Cone-specific expression of ADVM-062 in primates was confirmed using ADVM-062.myc, a vector engineered with the same regulatory elements as ADVM-062. Enumeration of human OPN1LW.myc-positive cones demonstrated that doses ≥3 × 1010 vg/eye resulted in transduction of 18%-85% of foveal cones. A Good Laboratory Practice (GLP) toxicology study established that IVT administration of ADVM-062 was well tolerated at doses that could potentially achieve clinically meaningful effect, thus supporting the potential of ADVM-062 as a one-time IVT gene therapy for BCM.

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson's Disease.

Directional deep brain stimulation (dDBS) is preferred by patients with advanced Parkinson's disease (PD) and by programming neurologists. However, real-life data of dDBS use is still scarce. We reviewed the clinical data of 53 PD patients with dDBS to 18 months of follow-up. Directional stimulation was favored in 70.5% of dDBS leads, and single segment activation (SSA) was used in 60% of dDBS leads. Current with SSA was significantly lower than with other stimulation types. During the 6-month follow-up, a 44% improvement in the Unified Parkinson's Disease Rating Scale (UPDRS-III) points and a 43% decline in the levodopa equivalent daily dosage (LEDD) was observed. After 18 months of follow-up, a 35% LEDD decrease was still noted. The Hoehn and Yahr (H&Y) stages and scores on item no 30 "postural stability" in UPDRS-III remained lower throughout the follow-up compared to baseline. Additionally, dDBS relieved non-motor symptoms during the 6 months of follow-up. Patients with bilateral SSA had similar clinical outcomes to those with other stimulation types. Directional stimulation appears to effectively reduce both motor and non-motor symptoms in advanced PD with minimal adverse effects in real-life clinical care.

Comprehensive Preclinical Assessment of ADVM-022, an Intravitreal Anti-VEGF Gene Therapy for the Treatment of Neovascular AMD and Diabetic Macular Edema.

Inhibition of vascular endothelial growth factor is the mode of action for several approved therapies, including aflibercept, for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Lack of compliance due to the frequent intravitreal dosing requirements may result in inadequately treated disease, leading to irreversible vision impairment. To date, the majority of gene therapy clinical trials providing sustained anti-VEGF levels in the retina have been limited to subretinal injections requiring a vitrectomy. A single intravitreal injection of a gene therapy product could drastically reduce the treatment burden and improve visual outcomes. ADVM-022, an adeno-associated virus vector encoding aflibercept, has been optimized for intravitreal delivery and strong protein expression. Long-term expression and efficacy of ADVM-022-derived aflibercept were evaluated in a laser-induced choroidal neovascularization (CNV) model in non-human primates. Ocular safety was evaluated following long-term suppression of VEGF by clinical scoring (inflammatory parameters) as well as optical coherence tomography (OCT) and electroretinography (ERG). Intravitreal administration of ADVM-022 was well tolerated and resulted in sustained aflibercept levels in ocular tissues. In addition, ADVM-022 administration 13 months before laser-induced CNV prevented the occurrence of clinically relevant CNV lesions, to the same degree as a bolus of aflibercept delivered at the time of laser. These results demonstrate that a single intravitreal administration of ADVM-022 may provide a safe and effective long-term treatment option for nAMD and DME, and may ultimately improve patients' visual outcomes. Clinical trials are currently underway, evaluating safety and efficacy following a single intravitreal injection of ADVM-022.

Long-Term Safety Evaluation of Continuous Intraocular Delivery of Aflibercept by the Intravitreal Gene Therapy Candidate ADVM-022 in Nonhuman Primates.

Purpose: To evaluate the long-term safety of vascular endothelial growth factor (VEGF) suppression with sustained aflibercept expression after a single intravitreal injection (IVI) of ADVM-022, an anti-VEGF gene therapy, in non-human primates (NHPs). Methods: Non-human primates received bilateral IVI of ADVM-022, a gene therapy vector encoding aflibercept, a standard of care for the treatment of VEGF-based retinal disease. Aflibercept levels from ocular fluids and tissues were measured. Ocular inflammation was assessed by slit lamp biomicroscopy and fundoscopy. The integrity of the retinal structure was analyzed by optical coherence tomography and blue light fundus autofluorescence and electroretinography was performed to determine retinal function. Histologic evaluation of the retina was performed at the longest time point measured (2.5 years after injection). Results: Sustained expression of aflibercept was noted out to the last time point evaluated. Mild to moderate inflammatory responses were observed, which trended toward spontaneous resolution without anti-inflammatory treatment. No abnormalities in retinal structure or function were observed, as measured by optical coherence tomography and electroretinography, respectively. RPE integrity was maintained throughout the study; no histologic abnormalities were observed 2.5 years after ADVM-022 IVI. Conclusions: In non-human primates, long-term, sustained aflibercept expression and the resulting continuous VEGF suppression by a single IVI of ADVM-022, appears to be safe, with no measurable adverse effects on normal retinal structure and function evaluated out to 2.5 years. Translational Relevance: Together with the results from previous ADVM-022 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for various VEGF-mediated ophthalmic disorders.

Management of Obstructive Hydrocephalus Associated with Pineal Region Cysts and Tumors and Its Implication in Long-Term Outcome.

BACKGROUND: Different treatment options have been proposed for obstructive hydrocephalus associated with pineal lesions. We discuss the obstructive hydrocephalus management associated with pineal region tumors and cysts in Helsinki Neurosurgery. METHODS: In this article, hydrocephalus treatment by tumor-cyst removal (n = 40), shunt surgery (n = 25), and endoscopic ventriculostomies (n = 3) is evaluated in 68 patients with obstructive hydrocephalus among 136 patients with pineal region tumor and cyst. Multivariate statistical analysis was followed by univariate and multivariate regression models of last functional status, last tumor-free imaging, and disease-specific mortality of the study population. RESULTS: Preoperative hydrocephalus was linked to higher World Health Organization tumor grades, poor functional status, higher mortality, and incomplete resection of pineal region cysts and tumors. Preoperative hydrocephalus remained a predictor of poor last functional status after multivariate regression. Pineal lesion removal with the posterior third ventricle opening as primary hydrocephalus treatment resulted in better last functional status, fewer postoperative shunts, fewer hydrocephalus-related procedures, and fewer postoperative infections than in the shunt-treatment group. Multivariate regression analysis linked higher World Health Organization tumor grade, poor immediate functional status, postoperative complications, and incomplete surgical resection as independent predictors of disease mortality in patients with hydrocephalus. Same variables (except immediate modified Rankin Scale score) and higher number of shunt surgeries became independent predictors of poor last functional status at multivariate analysis. Incomplete resection was the only independent predictor of tumor-free magnetic resonance imaging at the last evaluation. CONCLUSIONS: Direct removal of pineal lesions with the opening of the posterior third ventricle could represent effective and reliable management of the associated obstructive hydrocephalus. Further research is required to generalize our inferences.

Functional status of surgically treated pineal cyst patients.

BACKGROUND: Microsurgical removal represents a well-accepted treatment option for symptomatic benign pineal cysts (PCs). However, very few studies have quantitatively evaluated the functional status of surgically treated PC patients. METHODS: A detailed analysis of preoperative, immediate postoperative, and long-term clinical and radiological characteristics was performed. The functional status of the patients was categorized using the modified Rankin scale (mRS) and the Chicago Chiari Outcome Scale (CCOS). In addition, a comparative analysis between pediatric and adult patients with PCs was carried out. RESULTS: Overall, pediatric patients experienced better long-term mRS scores than adults. The differences between the pre-, the immediate post-, and the last postoperative mRS of the patients were statistically significant for the total population (P < 0.001). All patients obtained a CCOS of 11 or more, which reflects a good/optimal result after microneurosurgery. The type of the surgical approach was independently associated with the postoperative complications (P < 0.01), more frequently reported with the midline supracerebellar infratentorial (SCIT) approach than with its paramedian modification. CONCLUSION: The functional status of properly selected symptomatic patients with PCs may improve significantly after their surgical management through a paramedian SCIT approach in sitting position.

Analysis of Aflibercept Expression in NHPs following Intravitreal Administration of ADVM-022, a Potential Gene Therapy for nAMD.

Several standard-of-care therapies for the treatment of retinal disease, including aflibercept, inhibit vascular endothelial growth factor (VEGFA). The main shortcoming of these therapies is potential undertreatment due to a lack of compliance resulting from the need for repeated injections. Gene therapy may provide sustained levels of anti-VEGFA proteins in the retina following a single injection. In this nonhuman primate study, we explored whether ADVM-022, a recombinant adeno-associated virus (AAV) vector designed to express aflibercept, could induce anti-VEGFA protein levels comparable with those observed following a single-bolus intravitreal (IVT) injection of the standard-of-care aflibercept recombinant protein. The results demonstrated that intraocular levels of aflibercept measured at 56 days after a single IVT injection of ADVM-022 were equivalent to those in the aflibercept recombinant protein-injected animals measured 21-32 days post-administration. ADVM-022-injected animals exhibited signs of an initial self-limiting inflammatory response, but overall all doses were well tolerated. ADVM-022 administration did not result in systemic exposure to aflibercept at any dose evaluated. These results demonstrated that a single IVT injection of ADVM-022 resulted in safe and efficacious aflibercept levels in the therapeutic range, suggesting the potential of a gene therapy approach for long-term treatment of retinal disease with anti-VEGF therapy.

Systematic review of pineal cysts surgery in pediatric patients.

INTRODUCTION: We present a consecutive case series and a systematic review of surgically treated pediatric PCs. We hypothesized that the symptomatic PC is a progressive disease with hydrocephalus at its last stage. We also propose that PC microsurgery is associated with better postoperative outcomes compared to other treatments. METHODS: The systematic review was conducted in PubMed and Scopus. No clinical study on pediatric PC patients was available. We performed a comprehensive evaluation of the available individual patient data of 43 (22 case reports and 21 observational series) articles. RESULTS: The review included 109 patients (72% females). Ten-year-old or younger patients harbored smaller PC sizes compared to older patients (p < 0.01). The pediatric PCs operated on appeared to represent a progressive disease, which started with unspecific symptoms with a mean cyst diameter of 14.5 mm, and progressed to visual impairment with a mean cyst diameter of 17.8 mm, and hydrocephalus with a mean cyst diameter of 23.5 mm in the final stages of disease (p < 0.001). Additionally, 96% of patients saw an improvement in their symptoms or became asymptomatic after surgery. PC microsurgery linked with superior gross total resection compared to endoscopic and stereotactic procedures (p < 0.001). CONCLUSIONS: Surgically treated pediatric PCs appear to behave as a progressive disease, which starts with cyst diameters of approximately 15 mm and develops with acute or progressive hydrocephalus at the final stage. PC microneurosurgery appears to be associated with a more complete surgical resection compared to other procedures.

Long-term survival outcomes of pineal region gliomas.

PURPOSE: Surgical series of pineal region gliomas are rarely available. Whereas it is a general assumption that the extent of surgical resection correlates with survival outcomes of intracranial gliomas; the impact of the microsurgical resection on the long-term outcomes of pineal gliomas has been questioned. We present a surgical series of pineal region gliomas with focus on the survival outcome analysis. METHODS: 17 histologically confirmed pineal region glioma patients classified as diffuse and non-diffuse gliomas were retrospectively analyzed. A detailed description of the series was followed by regression models to identify predictors of clinical outcomes. Uni- a multivariate survival analysis was performed to determine independent predictors of mortality. RESULTS: Although the number of treated patients was small, only WHO grade histopathology remained significant (p = 0.02) after multivariate survival analysis with extent of resection, age, tumor volume, and preoperative functional status. The extent of the surgical resection did not correlate with the disease survival rates of non-diffuse (p = 1), diffuse (p = 0.2), nor all gliomas (p = 0.6). 15 of 17 patients underwent gross total (nine patients) or subtotal resection. The preoperative functional status of the patients showed overall improvement on the immediate (p < 0.001) and long-term (p = 0.03) follow-up after 106 (3 - 324) months. CONCLUSION: The extent of the surgical resection does not seem to significantly impact on the survival outcomes of pineal region gliomas. Thus, genotype and molecular features may essentially affect the outcome. Further research on the field is required.

Midline and Paramedian Supracerebellar Infratentorial Approach to The Pineal Region: A Comparative Clinical Study in 112 Patients.

OBJECTIVE: The midline supracerebellar infratentorial (SCIT) approach and its paramedian development are commonly used for dealing with pineal lesions. Comparative clinical studies are lacking, however. We aim to establish the better performance of the paramedian SCIT approach in terms of clinical safety in surgically treated pineal cysts and pineal region tumors. Procedural functionality and effectiveness have been also analyzed. METHODS: A comparative analysis of clinical, radiologic, pathologic, and surgical features, and outcome was performed between 55 midline and 57 paramedian SCIT approaches that were exclusively performed in 112 patients (57 pineal cysts and 55 tumors of the pineal region) operated in sitting position by a single surgeon. Information was retrieved from hospital records and microsurgical videos. RESULTS: The paramedian SCIT approach linked with fewer postoperative complications (odds ratio [OR]: 0.40) and fewer approach-related complications (OR: 0.28) than the midline SCIT approach. The SCIT paramedian approach was achieved in a shorter time, by a smaller bone flap, and with fewer complex procedural steps than the midline approach. The SCIT paramedian approach did not require the opening of the falx cerebelli, midline cerebellar retraction, section of the midline cerebellar draining veins, nor wide opening of the dura. Gross total resection, size of the lesion, microsurgical time for removal, histopathological diagnosis and postoperative outcome were statistically similar in both groups. CONCLUSIONS: The SCIT approach represents a safer and more functional approach for the removal of cysts and tumors of the pineal region than the classic midline approach, while maintaining the same effectiveness.

The microsurgical management of benign pineal cysts: Helsinki experience in 60 cases.

BACKGROUND: Microsurgical resection represents a well-accepted management option for symptomatic benign pineal cysts. Symptoms such as a headache, hydrocephalus, and visual deficiency are typically associated with pineal cysts. However, more recent studies reported over the past years have characterized additional symptoms as a part of the clinical manifestation of this disease and represent additional indications for intervention. METHODS: We present a retrospective review of patients with histologically confirmed benign pineal cysts that were operated on in our department between 1997 and 2015. A demographic analysis, evaluation of preoperative status, surgical treatment, as well as immediate and long-term clinical and radiological outcomes were conducted. RESULTS: A total of 60 patients with benign pineal cysts underwent surgery between 1997 and 2015. Gross total resection was achieved in 58 cases. All patients except one improved in their clinical status or had made a full recovery at the time of the last follow-up. The key steps for surgical resection of pineal cysts are reported, based on an analysis of representative surgical videos. CONCLUSIONS: We describe in this paper one of the largest series of microsurgically treated pineal cysts. In our opinion, judicious microsurgery remains the most suitable technique to effectively deal with this disease.

Extent of Resection and Long-Term Survival of Pineal Region Tumors in Helsinki Neurosurgery.

BACKGROUND: Pineal region tumors represent challenging surgical lesions with wide ranges of survival reported in different surgical series. In this article, we emphasize the role of complete microsurgical resection (CMR) to obtain a favorable long-term outcome of pineal region tumors. METHODS: We report a retrospective study of pineal region tumors operated on in Helsinki Neurosurgery between 1997 and 2015. Information was obtained from the hospital records, and an evaluation of the Finnish population register was conducted in July 2018 to determine the current status of the patients. RESULTS: A total of 76 pineal region tumors were operated on. The survival was 62% at a mean follow-up of 125 ± 105 months (range, 0-588 months), and the disease-related mortality was limited to 14 patients (18.4%). Up to July 2018, 29 patients had died. Two patients died 1 and 3 months after surgery of delayed thalamic infarctions, 12 patients of disease progression, and 15 had non-disease-related deaths. Only 1 patient was lost in the long-term follow-up. Ten of 14 disease-related deaths occurred during the first 5 years of follow-up: 5 diffuse gliomas, 3 germ cell tumors, 1 grade II-III pineal parenchymal tumor of intermediate differentiation, and 1 meningioma. CMR was linked to better tumor-free survival and long-term survival, with the exception of diffuse gliomas. CONCLUSIONS: CMR, in the setting of a multidisciplinary management of pineal region tumors, correlates with favorable survival and with minimal mortality. Surgically treated grade II-IV gliomas constitute a particular group with high mortality within the first 5 years independently of the microsurgical resection.

Pineal Parenchymal Tumors of Intermediate Differentiation: A long-Term Follow-Up Study in Helsinki Neurosurgery.

BACKGROUND: Pineal parenchymal tumors of intermediate differentiation (PPTIDs) are rare lesions with particular features compared with other pineal parenchymal tumors. METHODS: We present a retrospective review of patients with histologically confirmed PPTIDs who were operated on in our department between 1997 and 2015. A demographic analysis and an evaluation of preoperative status, surgical treatment, as well as immediate and long-term clinical and radiologic outcomes were conducted. RESULTS: Fifteen patients with PPTIDs were operated on between 1997 and 2015. Gross total removal was achieved in 11 cases; 2 patients underwent near-total resection, 1 partial resection, and 1 received brachytherapy after an endoscopic biopsy. Nine patients required external radiation therapy (4 due to a pleomorphic histology of their lesion including pineoblastoma features in 3 of them; 3 after a subtotal resection; and 2 for tumor recurrence). No patient received chemotherapy. The survival rate of our patients was 57.1% at a mean follow-up of 137.2 ± 77.6 months (39-248 months). CONCLUSIONS: A proper multidisciplinary management of PPTIDs based on a gross total removal of the lesion, and an adjuvant radiotherapy in selected cases, may improve the overall survival of these aggressive tumors.

Venous air embolisms and sitting position in Helsinki pineal region surgery.

BACKGROUND: Nowadays, the sitting position has lost favor among neurosurgeons partly due to assumptions of increased complications, such as venous air embolisms (VAEs) and hemodynamic disturbances. The aim of our study is to describe the importance of some anesthetic considerations and the utility of antigravity trousers as well, together with a skillful neurosurgery and an imperative proper teamwork, in order to prevent the risk of severe VAE during pineal region surgery. We routinely use them for the variant of the sitting position we developed, the "praying position." METHODS: A retrospective review of 51 pineal lesions operated on in the "praying position" using antigravity trousers was carried out. In the "praying position" the legs of the patient are kept parallel to the floor. Hence, antigravity trousers are used to generate an adequate cardiac preload. RESULTS: VAE associated to persistent hemodinamic changes was nonexistent in our series. The rate of VAE was 35.3%. VAEs were diagnosed mainly by monitoring of the end-tidal CO2 (83.33%). A venous system lesion was the cause in most of the cases. When VAE was suspected, an inmediate reaction based on a good teamwork was imperative. No cervical spine cord injury nor peripheral nerve damage were reported. The average microsurgical time was 48 ± 33 min. CONCLUSIONS: The risks of severe VAE during pineal region surgery in the "praying-sitting position" may be effectively prevented by some essential anesthetic considerations and the use of antigravity trousers together with a skillful neurosurgery, and an imperative proper teamwork.

Microsurgical Management of Vascular Malformations of the Pineal Region.

BACKGROUND: Vascular pineal malformations are rare and technically demanding lesions. Because the locations of these lesions, endovascular techniques and radiosurgery have been increasingly used in the recent decades to accomplish safe occlusion. Nevertheless, microsurgical treatment may be required sometimes. METHODS: We present a retrospective review of the vascular pineal malformations operated by the senior author. Moreover, we report illustrative cases for the various types of vascular lesions with a careful analysis of the different microsurgical stages. RESULTS: Eighteen patients with pineal vascular lesions were operated on between 1980 and 2015: 6 patients had vein of Galen malformations, 5 plexiform arteriovenous malformations, 6 cavernous malformations, and 1 patient had a ruptured medial posterior choroidal artery aneurysm. A complete resection and occlusion was possible in all vascular malformations. CONCLUSIONS: The pineal region is an infrequent but challenging location for vascular lesions. A careful and stepwise operative strategy for the different types of vascular lesion is paramount to accomplish an effective and safe microsurgical treatment when other alternatives fail or are not available.

Papillary Tumor of the Pineal Region in Children: Presentation of a Case and Comprehensive Literature Review.

BACKGROUND: Papillary tumor of the pineal region (PTPR) is a rare grade II-III pineal lesion with peculiar histological and immunohistochemical features. These tumors mostly occur in adults, only rarely in children, with 19 cases reported up to now. CASE DESCRIPTION: We present a 3-year-old boy who underwent reoperation for a recurrent PTPR (grade II). Gross total resection of the lesion through an occipital interhemispheric approach with the patient in a sitting position was followed by adjuvant radiotherapy and chemotherapy. Histological examination revealed tumor progression (grade III) and an MIB-1 proliferation index >25%. The patient continues to do well with no evidence of recurrence more than 3 years following surgery. A comprehensive literature review regarding the PTPR, including the current management in children, is reported. CONCLUSIONS: PTPRs are extremely rare in children, and immunohistochemistry is needed to differentiate them from other pineal tumors. These tumors show a high rate of recurrence, and a multidisciplinary management approach (microsurgical resection followed by radiotherapy and/or chemotherapy) can help achieve a favorable outcome.