Intraoperative Angiography

Enhancing Surgical Precision with Intraoperative Angiography: Real-time Visualization in Vascular and Neurosurgical Procedures

Multiple Choice Test: Intraoperative Angiography

  1. [ ] What is the primary purpose of intraoperative angiography?
    1. [ ] To monitor the patient’s vital signs during surgery.
    2. [x] To provide real-time visualization of blood vessels during surgery.
    3. [ ] To administer anesthesia to the patient.
    4. [ ] To remove blood clots from the bloodstream.
  1. [ ] Which imaging equipment is commonly used for intraoperative angiography?
    1. [ ] Magnetic resonance imaging (MRI)
    2. [ ] Ultrasound machine
    3. [x] C-arm fluoroscopy machine
    4. [ ] Electrocardiogram (ECG) machine
  1. [ ] How does intraoperative angiography contribute to surgical outcomes?
    1. [ ] It speeds up the surgery.
    2. [ ] It reduces the need for postoperative physical therapy.
    3. [x] It allows for immediate assessment and intervention, reducing complications.
    4. [ ] It eliminates the need for contrast dye injection.
  1. [ ] Which access site options are mentioned for intraoperative angiography?
    1. [ ] Transverse thoracic access
    2. [x] Transfemoral, transradial, and transulnar access
    3. [ ] Transcatheter aortic access
    4. [ ] Transcranial access
  1. [ ] What is the significance of using transradial and transulnar access sites for neuro-interventional procedures?
    1. [ ] They are more cost-effective.
    2. [ ] They provide better image quality.
    3. [x] They are safer and preferred by patients.
    4. [ ] They are only suitable for cardiac procedures.
  1. [ ] In which patient positions can intraoperative angiography be safely performed?
    1. [ ] Supine position only
    2. [x] Prone, three-quarters prone, and park-bench positions
    3. [ ] Sitting position
    4. [ ] Lateral decubitus position
  1. [ ] What are the indications for using intraoperative angiography?
    1. [ ] Diagnosis of diabetes
    2. [x] Aneurysm surgery and arteriovenous malformation surgery
    3. [ ] Orthopedic surgery
    4. [ ] Cosmetic surgery
  1. [ ] Which contrast agent can be used for intraoperative angiography to visualize surface vessels?
    1. [ ] Iodinated contrast
    2. [ ] Gadolinium
    3. [ ] Barium sulfate
    4. [x] Indocyanine green
  1. [ ] What is the main advantage of intraoperative digital subtraction angiography (ioDSA) in neurovascular procedures?
    1. [ ] It has a lower cost.
    2. [ ] It has a higher availability.
    3. [x] It is highly efficient and has a low risk of complications.
    4. [ ] It is suitable for all patients.
  1. [ ] Why might ioDSA be best suited for selected patients with complex neurovascular pathologies?
    1. [ ] Due to its lower cost and higher availability.
    2. [ ] Because it eliminates the need for other imaging modalities.
    3. [ ] Because it is faster than other angiography techniques.
    4. [x] Because it can potentially detect perfusion rests and remnants, leading to changes in the surgical strategy.

Intraoperative angiography is a valuable medical imaging technique used in vascular and neurosurgical procedures to provide real-time visualization of blood vessels. It involves the injection of contrast dye into the bloodstream and the use of specialized imaging equipment, such as C-arm fluoroscopy machines. Intraoperative angiography allows for immediate assessment of blood vessels, detection of abnormalities, and on-the-spot interventions to ensure optimal blood flow. It offers real-time feedback to surgical teams, reducing postoperative complications and improving surgical outcomes. The choice of access site, whether transfemoral, transradial, or transulnar, is influenced by safety and patient satisfaction considerations. Studies have shown that these alternative access sites are safe and effective for neuro-interventional procedures. Furthermore, the use of intraoperative angiography in various patient positions, such as prone or park-bench, has been found to be feasible and safe, with a notable rate of surgical adjustment/revision. Indications for intraoperative angiography include aneurysm surgery and arteriovenous malformation surgery, with options for contrast agents including traditional iodinated contrast and indocyanine green. The value of intraoperative angiography is particularly evident when used in combination with other imaging modalities, such as indocyanine green videoangiography. A risk-benefit analysis has shown that intraoperative digital subtraction angiography (ioDSA) is efficient, with low complication rates. IoDSA can potentially detect perfusion rests and remnants, leading to changes in the surgical strategy. However, due to its higher costs and lower availability compared to indocyanine green angiography, ioDSA may be best suited for selected patients with complex neurovascular pathologies.*

Overall, intraoperative angiography is a powerful tool that enhances surgical procedures, improves patient outcomes, and contributes to the safety and efficacy of neurovascular surgeries.


Keywords: Intraoperative angiography, medical imaging, real-time visualization, vascular surgery, neurosurgery, contrast dye, imaging equipment, real-time assessment, complications, outcomes, access, transfemoral approach, transradial access, transulnar access, safety, efficacy, prone position, indocyanine green, arteriovenous malformation, aneurysm, arteriovenous fistula, surgical microscope, robotic c-arm, risk-benefit analysis.

Intraoperative angiography is a medical imaging technique that is performed during surgery to visualize blood vessels in real time. It is particularly useful in various surgical procedures, especially those involving vascular surgery and neurosurgery. The goal of intraoperative angiography is to assess the patency, location, and integrity of blood vessels and make necessary adjustments or corrections during the surgical procedure.

Here’s how intraoperative angiography works:

Preparation: Before the surgery, the patient may be prepared by injecting a contrast dye into the bloodstream. This dye helps to make the blood vessels more visible on X-ray or fluoroscopy images.

Imaging Equipment: During the surgery, the surgeon uses specialized imaging equipment such as a C-arm fluoroscopy machine or a mobile angiography unit. The C-arm is a movable X-ray machine that can be positioned over the surgical area to capture real-time images.

Real-Time Imaging: The surgeon or a radiologic technologist can take X-ray images or perform fluoroscopy (continuous X-ray imaging) to visualize the blood vessels. The contrast dye in the bloodstream makes the vessels stand out on the images.

Assessment: Intraoperative angiography allows the surgeon to assess the blood flow, detect any obstructions or abnormalities, and ensure that the surgical procedure is proceeding as planned. For example, in vascular surgery, it can help identify stenoses (narrowing of blood vessels) or blockages.

Intervention: If a problem is identified, such as a blockage or aneurysm, the surgeon can take immediate corrective action, such as placing stents, removing clots, or reshaping blood vessels.

Confirmation: After the necessary adjustments or repairs have been made, another round of angiography is performed to confirm that the blood vessels are functioning properly. This step is crucial for assessing the success of the surgical procedure.

Intraoperative angiography has several advantages:

Real-time assessment: It provides immediate feedback to the surgical team, allowing them to adjust their actions as needed. Minimized complications: Identifying and addressing issues during surgery can reduce the risk of postoperative complications. Improved outcomes: Ensuring optimal blood flow can lead to better surgical outcomes, especially in procedures involving critical organs or vascular structures. However, it’s important to note that the use of X-ray radiation and contrast dye carries some inherent risks, so the benefits of intraoperative angiography must be carefully weighed against potential risks, and the procedure should be performed by skilled professionals with appropriate safety measures in place.

Historically, the transfemoral approach (TFA) has been the most common access site for cerebral intraoperative angiography (IOA). However, in line with trends in cardiac interventional vascular access preferences, the transradial access (TRA) and transulnar access (TUA) have been gaining popularity owing to favorable safety and patient satisfaction outcomes.

Tudor et al. compared the efficacy and safety of TRA/TUA and TFA for cerebral and spinal IOA at an institutional level over a 6-year period.

Methods: Between July 2016 and December 2022, 317 angiograms were included in our analysis, comprising 60 TRA, 10 TUA, 243 TFA, and 4 transpopliteal approach cases. Fluoroscopy time, contrast dose, reference air kerma, and dose-area products per target vessel catheterized were primary endpoints. Multivariate regression analyses were conducted to evaluate predictors of elevated contrast dose and radiation exposure and to assess time trends in access site selection.

Results: Contrast dose and radiation exposure metrics per vessel catheterized were not significantly different between access site groups when controlling for patient position, operative region, 3D rotational angiography use, and different operators. Access site was not a significant independent predictor of elevated radiation exposure or contrast dose. There was a significant relationship between case number and operative indication over the study period (P<0.001), with a decrease in the proportion of cases for aneurysm treatment offset by increases in total cases for the management of arteriovenous malformation, AVF, and moyamoya disease.

TRA and TUA are safe and effective access site options for neuro-interventional procedures that are increasingly used for IOA 1).

Vivanco-Suarez et al reviewed (between January 1960 and July 2022) all studies in which IOAs were performed during neurosurgical procedures with patients in either prone, three-quarters prone, or park-bench positions. Additionally, a cohort of patients from self-institutional experience was included. Efficacy outcomes were the rate of successful angiography and the rate of surgical adjustment/revision after IOA. Safety outcomes were the rate of angiography-related complications and mortality. Data were analyzed using a random-effects meta-analysis of proportions, and statistical heterogeneity was assessed.

A total of 26 studies with 142 patients plus 32 subjects from their own institutions were included in the analysis. The rate of successful intraoperative angiography was 98% (95% CI 94% to 99%; I2=0%). The rate of surgical adjustment/revision was 18% (95% CI 12% to 28%; I2=0%). The rate of complications related to the angiography was 1% (95% CI 0% to 5%; I2=0%). There were no deaths associated with IOA.

They found that IOA performed with patients in prone, three-quarters prone, and park-bench positions is feasible and safe with a non-negligible rate of intraoperative post-angiographical surgical adjustment/revision. The findings suggest that the performance of IOA to complement vascular neurosurgical procedures might have a valuable role in favoring patient outcomes 2).

Typically used in aneurysm surgery to confirm exclusion of the aneurysm from the circulation and to verify patency of critical adjacent vessels, and during AVM surgery to confirm total elimination of the nidus.

1. using traditional iodinated contrast and fluoroscopy. Requires use of Radiolucent Head Frame. Typically the introducer sheath is placed in the femoral artery at the time of initial pre-op angio, and is left in place for intraoperative use.

2. indocyanine green (ICG3) 4) : can be visualized under normal light, or sometimes to better advantage when illuminated with near-infrared light. Use is restricted to surface vessels. May be less reliable with giant or wide necked aneurysms or with thick walled atherosclerotic.


Among the different arterial accesses, the femoral access is the main approach for intraoperative angiography (IOA) performed in a prone position. Without a standardized protocol, however, the application of prone IOAs in intracranial arteriovenous malformation (AVM) or arteriovenous fistula (AVF) surgery remains limited by its procedural complexity 5).


Surgical microscope-integrated intraoperative angiography with intravenous injection of indocyanine green (ICG) has been widely used during bypass or aneurysm surgery. Instead of intravenous injection of ICG.

Intraoperative digital subtraction angiography (ioDSA) allows early treatment evaluation after neurovascular procedures. However, the value and efficiency of this procedure has been discussed controversially. Durner et al. from Günzburg, evaluated the additional value of hybrid operating room equipped with an Artis Zeego robotic c-arm regarding costefficiency and workflow. Furthermore, they performed a risk-benefit analysis and compared it with indocyanine green videoangiography.

For 3 consecutive years, they examined all neurovascular patients, treated in the hybrid operating theater in a risk-benefit analysis. After using microdoppler and ICG angiography for best operative result, every patient received an additional ioDSA to look for remnants or unfavorable clip placement which might lead to a change of operating strategy or results. Furthermore, a workflow-analysis reviewing operating steps, staff positioning, costs, technical errors or complications were conducted on randomly selected cases.

54 patients were enrolled in the risk-benefit analysis, 22 in the workflow analysis. The average duration of a cerebrovascular operation was 4 h 58 min 2 min 35 s accounted for ICG angiography, 46 min 4 s for ioDSA. Adverse events occurred during one ioDSA. In risk-benefit analysis, ioDSA was able to detect a perfusion rest in 2 out of 43 cases (4,7%) of aneurysm surgery, which could not have been visualized by ICG angiography before. In arterio-venous-malformation (AVM) surgery, one of 11 examined patients (7,7%) showed a remnant in ioDSA and resulted in additional resection. The average cost of an ioDSA in Ulm University can be estimated with 1928,00€.

According to the results ioDSA associated complications are low. Relevant findings in ioDSA can potentially avoid additional intervention, however, due to the high costs and lower availability, the main advantage might lie in the treatment of selected patients with complexes neurovascular pathologies since ICG angiography is equally safe but associated with lower costs and better availability 6).


1)

Tudor T, Sussman J, Sioutas GS, Salem MM, Muhammad N, Romeo D, Corral Tarbay A, Kim Y, Ng J, Rhodes IJ, Gajjar A, Hurst RW, Pukenas B, Bagley L, Choudhri OA, Zager EL, Srinivasan VM, Jankowitz BT, Burkhardt JK. Intraoperative angiography in neurosurgery: temporal trend, access site, and operative indication considerations from a 6-year institutional experience. J Neurointerv Surg. 2023 Oct 18:jnis-2023-020709. doi: 10.1136/jnis-2023-020709. Epub ahead of print. PMID: 37852753.
2)

Vivanco-Suarez J, Sioutas GS, Matache IM, Muhammad N, Salem MM, Kandregula S, Jankowitz BT, Burkhardt JK, Srinivasan VM. Intraoperative angiography during neurosurgical procedures on patients in prone, three-quarters prone, and park-bench positions: tertiary single-center experience with systematic review and meta-analysis. J Neurointerv Surg. 2023 Aug;15(8):793-800. doi: 10.1136/jnis-2022-020035. Epub 2023 Apr 17. PMID: 37068942.
3)

Raabe A, Nakaji P, Beck J, Kim LJ, Hsu FP, Kamerman JD, Seifert V, Spetzler RF. Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery. J Neurosurg. 2005; 103:982–989
4)

Dashti R, Laakso A, Niemela M, Porras M, Hernesniemi J. Microscope-integrated near-infrared indocyanine green videoangiography during surgery of intracranial aneurysms: the Helsinki experience. Surg Neurol. 2009; 71:543–50; discussion 550
5)

Wang C, Hsu SK, Chang CJ, Chen MH, Huang CT, Huang JS, Su IC. Transfemoral Approach for Intraoperative Angiography in the Prone or Three-quarter Prone Position : A Revisited Protocol for Intracranial Arteriovenous Malformation and Fistula Surgery. Clin Neuroradiol. 2019 Apr 29. doi: 10.1007/s00062-019-00783-3. [Epub ahead of print] PubMed PMID: 31037364.
6)

Durner G, Wahler H, Braun M, Kapapa T, Wirtz CR, König R, Pala A. The value of intraoperative angiography in the time of indocyanine green videoangiography in the treatment of cerebrovascular lesions: Efficacy, workflow, risk-benefit and cost analysis A prospective study. Clin Neurol Neurosurg. 2021 Apr 2;205:106628. doi: 10.1016/j.clineuro.2021.106628. Epub ahead of print. PMID: 33895619.

Olfactory groove schwannoma

Olfactory Groove Schwannoma: A Rare Intracranial Tumor – Case Studies and Review

Olfactory Groove Schwannoma Test

  1. What is the primary location of Olfactory Groove Schwannomas?
    1. [ ] a) Temporal lobe
    2. [x] b) Frontal lobe
    3. [ ] c) Occipital lobe
    4. [ ] d) Parietal lobe
  1. Which of the following is NOT a common symptom of Olfactory Groove Schwannoma?
    1. [ ] a) Anosmia
    2. [ ] b) Visual disturbances
    3. [x] c) Auditory hallucinations
    4. [ ] d) Headaches
  1. What is the primary treatment option for Olfactory Groove Schwannomas?
    1. [ ] a) Radiation therapy
    2. [ ] b) Chemotherapy
    3. [x] c) Surgical resection
    4. [ ] d) Medication
  1. Which of the following statements is true regarding Olfactory Groove Schwannomas?
    1. [x] a) They often originate from Schwann cells in the olfactory groove.
    2. [ ] b) They primarily affect the optic nerve.
    3. [ ] c) They are associated with frequent auditory deficits.
    4. [ ] d) They cannot be treated surgically.
  1. Olfactory Groove Schwannomas can sometimes be confused with which other tumors?
    1. [ ] a) Glioblastomas
    2. [x] b) Olfactory groove meningiomas
    3. [ ] c) Medulloblastomas
    4. [ ] d) Astrocytomas
  1. What is the typical outcome after complete surgical resection of an Olfactory Groove Schwannoma?
    1. [ ] a) Poor prognosis
    2. [ ] b) Neurological deficits
    3. [x] c) Favorable prognosis
    4. [ ] d) Olfactory dysfunction
  1. What is the primary goal of surgical resection in treating Olfactory Groove Schwannomas?
    1. [ ] a) Complete removal of the tumor with no concern for neurological function
    2. [x] b) Partial removal of the tumor while preserving neurological function
    3. [ ] c) Eliminating olfactory function
    4. [ ] d) None of the above
  1. According to the provided information, what is the controversial aspect of Olfactory Groove Schwannoma origin?
    1. [ ] a) They always originate from the olfactory nerve.
    2. [x] b) Their origin remains unknown.
    3. [ ] c) They originate from the optic nerve.
    4. [ ] d) They develop due to hormonal imbalances.
  1. In which cranial fossa are Olfactory Groove Schwannomas predominantly located?
    1. [ ] a) Middle cranial fossa
    2. [ ] b) Posterior cranial fossa
    3. [x] c) Anterior cranial fossa
    4. [ ] d) Inferior cranial fossa
  1. Which specific cells are responsible for the formation of Schwannomas?
    1. [ ] a) Oligodendrocytes
    2. [x] b) Schwann cells
    3. [ ] c) Neurons
    4. [ ] d) Astrocytes

Olfactory groove schwannoma is an uncommon intracranial tumor originating in the olfactory groove and is primarily associated with benign schwann cells. This review aims to provide insights into the clinical characteristics, diagnosis, treatment, and prognosis of this rare entity. Olfactory groove schwannomas are predominantly located in the anterior cranial fossa, often resulting in symptoms such as headaches, anosmia, visual disturbances, personality changes, and cognitive deficits. Diagnosis typically involves neuroimaging studies like MRI and CT scans. Surgical resection is the primary treatment option, with the goal of preserving neurological function, and sometimes complemented with radiation therapy for inoperable cases. While olfactory groove schwannomas are generally benign, each case presents unique challenges, and a multidisciplinary approach is essential for comprehensive patient care. Additionally, there is an ongoing debate about their origin, with both developmental and non-developmental hypotheses being proposed. Differential diagnosis should consider other tumors, such as olfactory groove meningiomas and esthesioneuroblastomas. This review also discusses case reports to shed light on the complex nature of olfactory groove schwannomas. Understanding the diverse aspects of this rare tumor is crucial for accurate diagnosis, management, and patient outcomes.


Keywords: Olfactory groove schwannomaanterior cranial fossadiagnosissurgical resectionprognosisdifferential diagnosiscase reports.

Olfactory groove schwannoma is a rare type of tumor that arises in the olfactory groove of the skull. Schwannomas are typically benign tumors that originate from Schwann cells, which are responsible for the formation of the myelin sheath covering nerves. When a schwannoma develops in the olfactory groove, it usually arises from the olfactory nerve or its branches.

Here are some key points about olfactory groove schwannomas:

Location: Olfactory groove schwannomas are found in the anterior cranial fossa, where the olfactory bulb and tract are located. They can grow and compress nearby structures, including the frontal lobes of the brain.

Symptoms: The symptoms of an olfactory groove schwannoma can vary depending on its size and location. Common symptoms may include headaches, changes in smell (anosmia), visual disturbances, personality changes, and cognitive deficits.

Diagnosis: Diagnosis often involves neuroimaging studies, such as magnetic resonance imaging (MRI) or computed tomography (CT) scans. These tests can help visualize the tumor and its impact on adjacent structures.

Treatment: The primary treatment for olfactory groove schwannomas is surgical resection. The goal of surgery is to remove the tumor while preserving neurological function. In some cases, a combination of microsurgery and endoscopy may be used to access and remove the tumor. Radiation therapy may be considered for residual or inoperable tumors.

Prognosis: Olfactory groove schwannomas are typically slow-growing and benign, which generally results in a favorable prognosis after surgical removal. The long-term outcome depends on factors such as the extent of tumor resection and the patient’s overall health.

Differential Diagnosis: Olfactory groove schwannomas may be mistaken for other tumors, such as olfactory groove meningiomas, which are more common in this region. A precise diagnosis is essential for determining the most appropriate treatment plan.

Multidisciplinary Approach: Managing olfactory groove schwannomas often requires a multidisciplinary approach involving neurosurgeons, otolaryngologists, and neurologists to provide comprehensive care.

It’s important to note that while olfactory groove schwannomas are generally benign, each case is unique, and treatment decisions should be made in consultation with a medical team specializing in neurosurgery and neuro-oncology.

According to past reports, subfrontal schwannomas are occasionally described as olfactory schwannomas or olfactory groove schwannomas.

Schwannoma arising from the olfactory system, often called olfactory groove schwannoma (OGS), is rare, as the olfactory bulb and tract, belonging to the central nervous system, should lack Schwann cells. Another rare entity called olfactory ensheathing cell tumor (OECT) has been reported, which mimics clinical and radiological characteristics of OGS.

They are very rare tumors, leaving the issue of their origin controversial.

In 94 patients with anterior skull base (ASB) and sinonasal schwannomas, 44 (46.8%) were exclusively sinonasal, 30 cases (31.9%) were exclusively intracranial, 12 (12.8%) were primarily intracranial with extension into the paranasal sinuses, and 8 (8.5%) were primarily sinonasal with intracranial extension 1).

Li et al. gathered previous literatures and reported that results in 35 cases of olfactory schwannomas (between 1974 and 2010) has shown that 14 out of 30 cases (47%) (with the exclusion of five cases due to unknown olfactory function) had preserved olfactory function, but that the remaining 16 (53%) experienced either anosmia or hyposmia. Regarding the attachment sites of the schwannomas, they summarized that 12 cases were on the cribriform plate, 10 cases were on the olfactory groove, and 5 cases were on the skull base and skull base dura. When the tumor was attached to the cribriform plate, the rate of olfaction preservation was relatively high [9 of 11 cases (82%), excluding one case due to unknown olfactory function], compared to olfactory groove attachment [2 of 7 cases (29%), excluding three cases due to unknown olfactory function].


Figueiredo et al. systematically reviewed the literature concerning the anterior cranial fossa schwannomas to understand their pathogenesis, determine their origin, and standardize the terminology. They performed a MEDLINE, EMBASE, and Science Citation Index Expanded search of the literature; age, gender, clinical presentation, presence or absence of hyposmia, radiological features, and apparent origin were analyzed and tabulated. Cases in a context of neurofibromatosis and nasal schwannomas with intracranial extension were not included. Age varied between 14 and 63 years (mean = 30.9). There were 22 male and 11 female patients. The clinical presentation included seizures (n = 15), headache (n = 16), visual deficits (n = 7), cognitive disturbances (n = 3), and rhinorrhea (n = 1). Hyposmia was present in 14 cases, absent in 13 cases (39.3%), and unreported in five. Homogeneous and heterogeneous contrast enhancement was observed in 14 and 15 cases, respectively. The region of the olfactory groove was the probable site in 96.5%. Olfactory tract could be identified in 39.3%. The most probable origin is the meningeal branches of trigeminal nerve or anterior ethmoidal nerves. Thus, olfactory groove schwannoma would better describe its origin and pathogenesis and should be the term preferentially used to name it 2).

Because the olfactory and optic nerves lack a Schwann cell layer, these are not prone to develop into a schwannoma.

Some hypotheses about the genesis of olfactory groove schwannoma are centered on its developmental and non-developmental origins.

The developmental hypotheses suggest whether mesenchymal pial cells to transform into ectodermal Schwann cells or neural crest cells to migrate within the substance of the central nervous system .

The non-developmental hypotheses postulate that intracranial schwannomas arise from the Schwann cells normally presenting in the adjacent structures, such as the perivascular nerve plexus, the meningeal branches of the trigeminal and anterior ethmoidal nerves innervating the anterior cranial fossa and olfactory groove 3) 4).

Yasuda et al. 5) proposed the concept of an olfactory ensheathing cell (OEC) tumor in 2006. Olfactory ensheathing cells are glial cells that ensheath the axons of the first cranial nerve. Microscopically, both olfactory ensheathing cells and Schwann cells have similar morphological and immunohistochemical features. However, immunohistochemically olfactory ensheathing cells are negative for Leu7 and Schwann cells positive 6).

Often, these tumors can be confused for other entities, especially olfactory groove meningiomas and esthesioneuroblastoma7).

Because most olfactory region schwannomas have a benign nature, a complete resection of the tumor is the treatment of choice, and adjunctive therapy is not usually required 8) 9).

With the recent advances in endoscopic skull base surgery, various anterior skull base tumors (ASB) can be resected successfully using an expanded endoscopic endonasal transcribriform approach through a “keyhole craniectomy” in the ventral skull base. This approach represents the most direct route to the anterior cranial base without any brain retraction. Tumor involving the paranasal sinuses, medial orbits, and cribriform plate can be readily resected. In a video atlas report, Liu and Eloy demonstrate their step-by-step techniques for resection of an ASB olfactory schwannoma using a purely endoscopic endonasal transcribriform approach. They describe and illustrate the operative nuances and surgical pearls to safely and efficiently perform the approach, tumor resection, and multilayered reconstruction of the cranial base defect. The video can be found here: http://youtu.be/NLtOGfKWC6U 10).

Endoscopic Endonasal Anterior Cranial Fossa Approach 11)

The prognosis after complete resection is known to be favorable 12).

When the tumor is attached to the cribriform plate, the preservation rate of olfactory function is higher compared to nearby structures 13).

A 65-year-old male patient who presented with olfactory groove meningioma and non-functioning pituitary adenoma as a collision tumor. The patient was admitted with a headache and right-sided vision loss. The patient’s first neurologic examination was consistent with temporal anopsia in the right eye. Subsequent contrast-enhanced cranial MRI revealed a 65x55x40 mm heterogeneously contrast-enhanced lesion in the anterior skull base extending from the sellar region to the corpus callosum. Because of the tumor size, a two-staged operation was planned. First, the tumor was partially excised via a right frontal craniotomy with a transcranial approach, and the tumor in the sellar region was left as a residue. The pathology reports after the first surgery showed pituitary adenoma and meningeal epithelial type meningioma (WHO Grade I). The residual tumor tissue was resected seven months later via an endoscopic endonasal approach, except for the part that invaded the right anterior cerebral artery. The optic nerve was decompressed. The patient was then referred to the radiation oncology clinic for radiosurgery. Collision tumors should be considered in the differential diagnosis in preoperative evaluation and surgical planning when heterogeneously contrast-enhanced areas significantly localized adjacent to each other are seen on cranial MRI. On the other hand, when the surgeon encounters sudden changes in the appearance or consistency of the tumor during the surgery, they should suspect these tumor complexes. The diagnosis of collision tumors is quite challenging but is of great importance regarding the patient’s need for postoperative radiation therapy or the recurrence characteristics of tumors. However, more studies are needed on these complexes’ etiology, surgical planning, and postoperative management 14).


A 59-year-old woman who presented with a paroxysmal headache for 1 year. The tumor appeared as hypointensity on T1-weighted images, hyperintensity on T2-weighted, and exhibited strong, heterogeneous enhancement. The tumor was removed through a lateral supraorbital approach. The final pathologic diagnosis was schwannoma. The postoperative period was uneventful after 4 months, and the headache disappeared 15).


2016

Bohoun et al report two rare cases of schwannoma-like tumor in the anterior cranial fossa that showed negative staining for Leu7, but positive staining for Schwann/2E, and discuss their origin. Two cases of mass lesions in the anterior cranial fossa in a 26-year-old man and a 24-year-old woman were successfully removed. Morphological examination of these tumors was compatible with a diagnosis of schwannoma. Immunohistochemically, both cases were negative for Leu7, yielding a diagnosis of olfactory ensheathing cell tumor (OECT), but were positive for the schwannoma-specific marker, Schwann/2E. Immunohistochemical staining results in this two cases question the current assumption that OGS and OECT can be distinguished only by Leu7 staining pattern. In conclusion, the origins of OGS and OECT remain to be determined, and further studies in larger numbers of cases are needed to characterize these rare tumors in the anterior cranial fossa 16)

2015

A case of a 49-year-old woman with an olfactory groove schwannoma attached to the cribriform plate without olfactory dysfunction. She had no specific neurological symptoms other than a headache, and resection of the tumor showed it to be a schwannoma. About 19 months after the operation, a follow-up MRI showed no evidence of tumor recurrence. Surgical resection through subfrontal approach could be one of the curative modality in managing an olfactory groove schwannoma. An olfactory groove schwannoma should be considered in the differential diagnosis of anterior skull base tumors 17).

2014

Okamoto et al. report two cases of subfrontal schwannomas treated with surgical resection. In one case, the tumor was located between the endosteal and meningeal layers of the dura mater. This rare case suggests that subfrontal schwannomas may originate from the fila olfactoria 18).


A 24 year old lady presented with hemifacial paraesthesias. Radiology revealed a large olfactory region enhancing lesion. She was operated through a transbasal approach with olfactory preservation. 19).


One patient had intradural intracranial extension and required an extended endoscopic endonasal transcribriform approach with anterior skull base resection 20).

2013

A 66-year-old woman presented with a 1-year history of progressive headaches. Clinical examination revealed hypoesthesia of the nasal tip. CT-scan and MRI studies revealed a large subfrontal tumor thought preoperatively to be a meningioma. Intraoperatively, a large extra-axial tumor arising from the floor of the right frontal fossa was encountered. Histopathology identified the tumor as a schwannoma. This current case gives strong clinical presumption of an origin from the anterior ethmoidal nerve. We reviewed the literature in order to establish the epidemiology of these tumors, from which there appear to be divergent profiles depending on tumor origin and histology. Despite close similarities with olfactory groove meningiomas, patient history and radiological findings provide substantial evidence for differential diagnosis 21).

2012

Liu and Eloy demonstrate their step-by-step techniques for resection of an ASB olfactory schwannoma using a purely endoscopic endonasal transcribriform approach.


A case of schwannoma arising from the olfactory groove in a 16-year-old girl who presented with generalized seizures without olfactory dysfunction or other neurologic deficits. Computerized tomography (CT) scan showed a large mass with abundant calcification located in the olfactory groove, which was confirmed as a schwannoma by histology and totally resected via basal subfrontal approach.

The tumor was attached to the cribriform plate, and achieved gross total resection without compromising her olfactory function 22).

In conclusion, understanding the diverse aspects of olfactory groove schwannomas is crucial for accurate diagnosis, effective management, and improved patient outcomes. This rare tumor entity serves as a reminder of the complexity of intracranial pathologies and the need for ongoing research to better comprehend its origin and pathogenesis.


1)

Sunaryo PL, Svider PF, Husain Q, Choudhry OJ, Eloy JA, Liu JK. Schwannomas of the sinonasal tract and anterior skull base: a systematic review of 94 cases. Am J Rhinol Allergy. 2014 Jan-Feb;28(1):39-49. doi: 10.2500/ajra.2014.28.3978. Review. PubMed PMID: 24717879.
2)

Figueiredo EG, Soga Y, Amorim RL, Oliveira AM, Teixeira MJ. The puzzling olfactory groove schwannoma: a systematic review. Skull Base. 2011 Jan;21(1):31-6. doi: 10.1055/s-0030-1262945. PubMed PMID: 22451797; PubMed Central PMCID: PMC3312416.
3)

Shenoy SN, Raja A. Cystic olfactory groove schwannoma. Neurol India. 2004;52:261–262.
4)

Li YP, Jiang S, Zhou PZ, Ni YB. Solitary olfactory schwannoma without olfactory dysfunction: a new case report and literature review. Neurol Sci. 2012;33:137–142.
5)

Yasuda M, Higuchi O, Takano S, Matsumura A. Olfactory ensheathing cell tumor: a case report. J Neurooncol. 2006;76:111–113.
6)

Yamaguchi T, Fujii H, Dziurzynski K, Delashaw JB, Watanabe E. Olfactory ensheathing cell tumor: case report. Skull Base. 2010 Sep;20(5):357-61. doi: 10.1055/s-0030-1249572. PubMed PMID: 21359000; PubMed Central PMCID: PMC3023328.
7)

Khandwala K, Alam MM, Ashfaq Z, Hilal K. Olfactory schwannoma masquerading as esthesioneuroblastoma. BMJ Case Rep. 2023 Oct 18;16(10):e257847. doi: 10.1136/bcr-2023-257847. PMID: 37852667.
8)

Carron JD, Singh RV, Karakla DW, Silverberg M. Solitary schwannoma of the olfactory groove: case report and review of the literature. Skull Base. 2002;12:163–166.
9) , 12)

Choi YS, Sung KS, Song YJ, Kim HD. Olfactory schwannoma-case report- J Korean Neurosurg Soc. 2009;45:103–106.
10)

Liu JK, Eloy JA. Expanded endoscopic endonasal transcribriform approach for resection of anterior skull base olfactory schwannoma. J Neurosurg. 2012 Jan;32 Suppl:E3. PubMed PMID: 22251251.
11)

Candelo E, Otamendi-Lopez A, Chaichana KL, Donaldson AM. Endoscopic Endonasal Anterior Cranial Fossa Approach for Rare Giant Olfactory Schwannoma Resection. Oper Neurosurg (Hagerstown). 2023 Sep 25. doi: 10.1227/ons.0000000000000921. Epub ahead of print. PMID: 37747334.
13) , 17)

Kim DY, Yoon PH, Kie JH, Yang KH. The olfactory groove schwannoma attached to the cribriform plate: a case report. Brain Tumor Res Treat. 2015 Apr;3(1):56-9. doi: 10.14791/btrt.2015.3.1.56. Epub 2015 Apr 29. PubMed PMID: 25977910; PubMed Central PMCID: PMC4426280.
14)

Aydin MV, Yangi K, Toptas E, Aydin S. Skull Base Collision Tumors: Giant Non-functioning Pituitary Adenoma and Olfactory Groove Meningioma. Cureus. 2023 Sep 5;15(9):e44710. doi: 10.7759/cureus.44710. PMID: 37809125; PMCID: PMC10552590.
15)

Guo W, Liu Z, Wang Z, Tian H, Zi X. Olfactory Groove Schwannoma or Olfactory Ensheathing cell Tumor? J Craniofac Surg. 2023 Aug 29. doi: 10.1097/SCS.0000000000009705. Epub ahead of print. PMID: 37643126.
16)

Bohoun CA, Terakawa Y, Goto T, Tanaka S, Kuwae Y, Ohsawa M, Morisako H, Nakajo K, Sato H, Ohata K, Yokoo H. Schwannoma-like tumor in the anterior cranial fossa immunonegative for Leu7 but immunopositive for Schwann/2E. Neuropathology. 2016 Dec 7. doi: 10.1111/neup.12357. [Epub ahead of print] PubMed PMID: 27925298.
18)

Okamoto H, Mineta T, Wakamiya T, Tsukamoto H, Katsuta T, Nakagaki H, Matsushima T. Two cases of subfrontal schwannoma, including a rare case located between the endosteal and meningeal layers of the dura. Neurol Med Chir (Tokyo). 2014;54(8):681-5. Epub 2013 Dec 5. PubMed PMID: 24305023.
19)

Salunke P, Patra DP, Futane S, Nada R. Olfactory region schwannoma: Excision with preservation of olfaction. J Neurosci Rural Pract. 2014 Jul;5(3):281-3. doi: 10.4103/0976-3147.133600. PubMed PMID: 25002774; PubMed Central PMCID: PMC4078619.
20)

Blake DM, Husain Q, Kanumuri VV, Svider PF, Eloy JA, Liu JK. Endoscopic endonasal resection of sinonasal and anterior skull base schwannomas. J Clin Neurosci. 2014 Aug;21(8):1419-23. doi: 10.1016/j.jocn.2014.03.007. Epub 2014 May 5. PubMed PMID: 24810934.
21)

Sauvaget F, François P, Ben Ismail M, Thomas C, Velut S. Anterior fossa schwannoma mimicking an olfactory groove meningioma: case report and literature review. Neurochirurgie. 2013 Apr;59(2):75-80. doi: 10.1016/j.neuchi.2013.02.003. Epub 2013 Apr 13. Review. PubMed PMID: 23587626.
22)

Li YP, Jiang S, Zhou PZ, Ni YB. Solitary olfactory schwannoma without olfactory dysfunction: a new case report and literature review. Neurol Sci. 2012 Feb;33(1):137-42. doi: 10.1007/s10072-011-0573-9. Epub 2011 Apr 12. Review. Erratum in: Neurol Sci. 2012 Feb;33(1):217. PubMed PMID: 21484358; PubMed Central PMCID: PMC3275737.

Carotid cavernous fistula coil embolization

Carotid cavernous fistula coil embolization

Carotid cavernous fistula (CCF) coil embolization is a crucial medical procedure designed to address the abnormal connection between the carotid artery and the cavernous sinus, often resulting in abnormal blood flow and elevated pressure within the cavernous sinus. This connection can lead to various neurological symptoms and potential complications.

This review discusses the key steps involved in CCF coil embolization, including diagnostic angiography, guidewire placement, catheter insertion, coil placement, and post-procedure monitoring. The primary objective of this procedure is to effectively close the abnormal connection, restoring normal blood flow and alleviating CCF-related symptoms.

Furthermore, the review highlights complications associated with different venous approaches, such as cranial nerve injury, vascular dissections, and perforations. It emphasizes the significance of careful patient selection and technique to minimize these complications.

The use of detachable balloons in the treatment of direct CCFs is also explored, providing insights into their role in achieving successful embolization. Clinical outcomes and angiographic cure rates are discussed based on case series and reports, offering valuable information for healthcare practitioners and researchers.

In conclusion, carotid cavernous fistula coil embolization is an essential intervention performed by specialized medical professionals. This review provides a comprehensive overview of the procedure, its complications, and outcomes, facilitating a better understanding of the treatment and its effectiveness in managing CCF.

Carotid cavernous fistula (CCF) coil embolization is a medical procedure used to treat a carotid cavernous fistula, which is an abnormal connection between the carotid artery and the cavernous sinus in the brain. This connection can lead to abnormal blood flow and pressure in the cavernous sinus, which can cause a range of neurological symptoms and potential complications.

The goal of coil embolization is to close off the abnormal connection between the carotid artery and the cavernous sinus, thus restoring normal blood flow and relieving the symptoms associated with the CCF. Here’s how the procedure typically works:

Diagnostic Angiography: The first step is usually a diagnostic angiography, during which a contrast dye is injected into the blood vessels, and X-ray imaging is used to visualize the blood vessels in the head and neck. This helps the medical team locate the exact site of the CCF and assess its size and characteristics.

Guidewire Placement: A thin, flexible guidewire is threaded through a catheter and advanced through the blood vessels to reach the site of the CCF.

Catheter Insertion: A catheter, which is a long, thin tube, is then inserted into the blood vessel and guided to the location of the CCF.

Coil Placement: Platinum coils or other embolic devices are delivered through the catheter to the site of the CCF. These coils are designed to create a barrier that blocks the abnormal blood flow and encourages the formation of a blood clot to seal off the fistula.

Check and Repeat: The medical team will use imaging, typically fluoroscopy, to ensure that the coils are properly placed and that the CCF is effectively blocked. In some cases, additional coils may be needed to achieve complete closure.

Removal of Catheter: Once the CCF is successfully embolized, the catheter and guidewire are removed from the blood vessels.

Post-procedure Monitoring: After the procedure, patients are typically observed in a recovery area and monitored for a period to check for any immediate complications. They may also receive anticoagulant medications to prevent clot formation at the coil site.

Recovery time and the specific details of the procedure can vary depending on the individual case and the severity of the CCF. Patients may need to stay in the hospital for a period of observation, and they will be closely monitored for potential complications. Long-term follow-up is essential to assess the effectiveness of the coil embolization and to ensure that the CCF does not reoccur.

It’s important to note that this procedure is performed by interventional radiologists or neurosurgeons with expertise in vascular malformations, and the choice of treatment method depends on the specific characteristics of the CCF and the patient’s overall health.

Complications associated with different venous approaches are injury of the cranial nerves due to the dense packing of the CS with coils as well as vascular dissections and perforations 1).


One case (3.2%) experienced procedure-related complication presented with transient oculomotor nerve palsy 2)


The use of Onyx is not exempt from complications such as transient compressive neuropathies or cranial nerve ischemia/infarction caused by post-embolization CS thrombosis and penetration within arterial collaterals, respectively 3)


Acquired proptosis and progressive abducens nerve palsy due to overpacked coiling material: rare sequelae of carotid cavernous fistula embolization 4).

Plasencia and Santillan report ther experience using the endovascular technique in 24 patients harboring 25 CCFs treated between October 1994 and April 2010, with an emphasis on the role of detachable balloons for the treatment of direct CCFs.

Of the 16 patients who presented with direct CCFs (Barrow Type A CCFs) (age range, 7-62 years; mean age, 34.3 years), 14 were caused by traumatic injury and 2 by a ruptured internal carotid artery (ICA) aneurysm. Eight patients (age range, 32-71 years; mean age, 46.5 years) presented with nine indirect CCFs (Barrow Types B, C, and D). The clinical follow-up after endovascular treatment ranged from 2 to 108 months (mean, 35.2 months). In two cases (8%), the endovascular approach failed. Symptomatic complications related to the procedure occurred in three patients (12.5%): transient cranial nerve palsy in two patients and a permanent neurological deficit in one patient. Detachable balloons were used in 13 out of 16 (81.3%) direct CCFs and were associated with a cure rate of 92.3%. Overall, the angiographic cure rate was obtained in 22 out of 25 (88%) fistulas. Patients presenting with III nerve palsy improved gradually between 1 day and 6 months after treatment. Good clinical outcomes [modified Rankin scale (mRS) ≤ 2] were observed in 22 out of 24 (91.6%) patients at last follow-up 5)

Teoh et al. reported a acquired proptosis and progressive abducens nerve palsy due to overpacked coiling material: rare sequelae of carotid cavernous fistula embolization 6).


An 84-year-old woman presented to her local emergency room for diplopia and loss of visual acuity. Computed tomography (CT) of the head and CT angiography (CTA) showed no infarction, but the CTA revealed enlarged superior ophthalmic veins, suggesting a CCF (Figure 1). The emergency department referred her to Interventional Neuroradiology for treatment options. Physicians in the oculoplastics service also saw her before the procedure. Cerebral angiography was performed via the right femoral approach, demonstrating an indirect CCF supplied by small branches of both the right and left ICAs as well as ECA branches with primary venous drainage into the right superior ophthalmic vein. Immediately after the diagnosis of CCF was confirmed on diagnostic transfemoral arterial angiogram, a transfemoral venous approach was used in an attempt to treat the CCF via the jugular veins and the inferior petrosal sinus (IPS). This approach was unsuccessful because the IPS was completely occluded bilaterally. The patient returned for definitive treatment with the assistance of the ophthalmology department. In the angiography suite, the oculoplastic surgeon performed a cut down to expose the right superior ophthalmic vein.3 The neurointerventionalist then punctured the exposed vein with a micropuncture needle to advance an 0.018-inch guidewire into the cavernous sinus. A 4-French sheath was placed over the wire into the vein with its tip terminating at the midportion of the dilated superior ophthalmic vein. A Penumbra PX SLIM (Alameda, CA) microcatheter was then advanced over a microwire, and coils were used to occlude the cavernous sinus starting in the posterior cavernous sinus and extending forward into the superior and inferior ophthalmic veins. The neurointerventionalist deployed 150 cm of Penumbra 0.020-inch caliber detachable coils to occlude the CCF. During follow-up clinic visits, the patient’s vision showed continued improvement. Her visual acuity improved on postoperative day 1, and she showed further improvement on later clinic visits. Her diplopia slowly improved, and her proptosis also decreased. She had a cranial nerve VI palsy that improved by 50% at 3 months. Her chemosis resolved with treatment as well. 7).

What is the primary objective of carotid cavernous fistula (CCF) coil embolization?

a. To diagnose CCF-related symptoms b. To create an abnormal connection between the carotid artery and the cavernous sinus c. To close the abnormal connection between the carotid artery and the cavernous sinus d. To monitor blood flow within the cavernous sinus

Which of the following is NOT one of the key steps involved in CCF coil embolization?

a. Diagnostic angiography b. Guidewire placement c. Catheter insertion d. Direct intracranial surgery

What is the role of platinum coils or embolic devices in CCF coil embolization?

a. To diagnose the size of the CCF b. To block the abnormal blood flow and encourage blood clot formation c. To provide anticoagulant medications to patients d. To monitor the patient’s recovery

Why is post-procedure monitoring important in CCF coil embolization?

a. To assess the effectiveness of the coils b. To determine the size of the catheter c. To ensure the patient is comfortable during recovery d. To create a direct connection between the carotid artery and the cavernous sinus

What type of medical professionals typically perform CCF coil embolization?

a. General practitioners b. Cardiologists c. Interventional radiologists or neurosurgeons d. Ophthalmologists

Which of the following complications can be associated with CCF coil embolization?

a. Improved vision b. Cranial nerve injury c. Reduced blood pressure d. Normal blood flow in the cavernous sinus

What is the significance of detachable balloons in CCF coil embolization?

a. They are used to inflate the patient’s blood vessels. b. They help diagnose complications. c. They assist in achieving successful embolization. d. They are used to monitor cranial nerve function.

What is the purpose of a comprehensive review of CCF coil embolization?

a. To create a detailed treatment plan for patients b. To assess the cost of the procedure c. To provide a thorough examination of existing literature on the topic d. To promote awareness of CCF coil embolization among the public

Answers:

c. To close the abnormal connection between the carotid artery and the cavernous sinus d. Direct intracranial surgery b. To block the abnormal blood flow and encourage blood clot formation a. To assess the effectiveness of the coils c. Interventional radiologists or neurosurgeons b. Cranial nerve injury c. They assist in achieving successful embolization. c. To provide a thorough examination of existing literature on the topic


1)

Oishi H, Arai H, Sato K, Iizuka Y. Complications associated with transvenous embolisation of cavernous dural arteriovenous fistula. Acta Neurochir (Wien). 1999;141(12):1265-71. doi: 10.1007/s007010050429. PMID: 10672296.
2)

Ma Y, Li Z, Zhang T, Chen H, Chen X, Zhao W. Efficiency of endovascular management with a combination of Onyx and coils for direct and indirect carotid cavernous fistula treatment: Experience of a single center. Clin Neurol Neurosurg. 2023 May;228:107700. doi: 10.1016/j.clineuro.2023.107700. Epub 2023 Mar 27. PMID: 36996671.
3)

Elhammady MS, Wolfe SQ, Farhat H, Moftakhar R, Aziz-Sultan MA. Onyx embolization of carotid-cavernous fistulas. J Neurosurg. 2010 Mar;112(3):589-94. doi: 10.3171/2009.6.JNS09132. PMID: 19591548.
4) , 6)

Teoh RJJ, Ain Masnon N, Bahari NA, Ch’ng LS. Acquired proptosis and progressive abducens nerve palsy due to overpacked coiling material: rare sequelae of endovascular treatment for carotid cavernous fistula. BMJ Case Rep. 2023 Oct 10;16(10):e255406. doi: 10.1136/bcr-2023-255406. PMID: 37816571.
5)

Plasencia AR, Santillan A. Endovascular embolization of carotid-cavernous fistulas: A pioneering experience in Peru. Surg Neurol Int. 2012;3:5. doi: 10.4103/2152-7806.92167. Epub 2012 Jan 21. PMID: 22363900; PMCID: PMC3279962.
7)

Pansara A, Milburn JM, Perry M, Eubanks B. Clinical images – a quarterly column: transorbital coil embolization of a carotid cavernous fistula. Ochsner J. 2013 Fall;13(3):295-7. PMID: 24052755; PMCID: PMC3776501.

Omental flap transplantation for Moyamoya disease

  1. What is Moyamoya disease characterized by? a) Progressive stenosis and occlusion of coronary arteries b) Progressive stenosis and occlusion of internal carotid arteries c) Progressive stenosis and occlusion of pulmonary arteries d) Progressive stenosis and occlusion of femoral arteries
  2. Why is cerebral revascularization important in Moyamoya disease? a) To treat high blood pressure b) To improve blood flow and prevent stroke c) To reduce cholesterol levels d) To manage migraines
  3. What is the traditional approach for harvesting the omental flap for revascularization in Moyamoya disease? a) Laparoscopy b) Angiography c) Laparotomy d) Endoscopy
  4. In the systematic review, how many studies met the inclusion criteria? a) Two b) Three c) Four d) Five
  5. What were the key outcomes of interest in the systematic review? a) Intraoperative and postoperative complications b) Length of hospital stay and surgical technique c) Blood pressure management and postoperative complications d) Postoperative complications and long-term outcomes
  6. What percentage of patients in the systematic review experienced intraoperative complications? a) 3% b) 7.3% c) 10% d) 15%
  7. What is the average length of hospital stay reported in the systematic review? a) 2.0 days b) 4.5 days c) 6.2 days d) 8.0 days
  8. What is the main conclusion drawn from the systematic review regarding laparoscopic omental flap revascularization in Moyamoya disease? a) Laparoscopy is not a suitable approach. b) Laparoscopy has a high rate of intraoperative complications. c) Laparoscopic omental flap mobilization is safe and effective. d) Laparoscopy is only suitable for adult patients.
  9. In one of the referenced studies, what additional imaging technique was used to assess the viability of the omental flap? a) CT scan b) X-ray c) MRI d) Intraoperative fluorescence imaging using indocyanine green
  10. According to the study by Ohtaki et al., what is the range of the clinical observation period for pediatric moyamoya patients who underwent omental transplantation? a) 1.9 to 6.7 years b) 6.7 to 9.2 years c) 1.9 to 10 years d) 0.9 to 5.2 years

Answers:

  1. b) Progressive stenosis and occlusion of internal carotid arteries
  2. b) To improve blood flow and prevent stroke
  3. c) Laparotomy
  4. d) Five
  5. d) Postoperative complications and long-term outcomes
  6. b) 7.3%
  7. c) 6.2 days
  8. c) Laparoscopic omental flap mobilization is safe and effective.
  9. d) Intraoperative fluorescence imaging using indocyanine green
  10. b) 6.7 to 9.2 years

    In patients with Moyamoya diseasecerebral revascularization using a pedicled omental flap has proven to be a viable option following direct revascularization procedures. Historically, harvesting omentum involved laparotomy with the associated risk of complications; herein we describe outcomes from a 10-year experience of laparoscopic harvesting of pedicled omental flap for cerebral revascularization in Moyamoya patients.

    Methods: A retrospective chart review was performed of all patients with Moyamoya disease who underwent laparoscopic omental cerebral transposition between 2011 and 2021. Intraoperative and postoperative complications, length of stay (LOS), and outcomes at follow-up were analyzed.

    Results: Twenty-one patients underwent the procedure during the study period. Three intraoperative complications occurred (one segmental transverse colectomy for mesenteric injury, one converted to omental free flap, and one requiring micro anastomosis). The average overall LOS was 6 ± 6 days, with 3 ± 3.5 days in the ICU (mean±SD). Following discharge, complications included epigastric incisional hernia at the graft fascial exit site, recurrent neck pain at the subcutaneous tunneling site, and partial scalp necrosis. One patient required subsequent direct bypass seven months after the initial procedure owing to the progression of the disease. All other patients had partial or complete resolution of symptoms.

    Conclusion: Our retrospective observational study indicates that laparoscopic pedicled omental flap mobilization and transposition is a safe and effective method of indirect cerebral revascularization in patients with Moyamoya disease 1)


    report our techniques and outcomes in 2 adults with Moyamoya to undergo such a procedure. An omental flap based on the right gastroepiploic artery was created and intraoperative fluorescence imaging using indocyanine green was used to assess the viability of the flap and to guide lengthening of the pedicle. The flap was tunneled subcutaneously using skip incisions. There were no intraoperative complications and no postoperative complications related to the omental flap. Follow-up evaluation demonstrates viable omental flaps and improved cerebral vascularization. This technique is feasible in adults who require salvage cerebral revascularization for Moyamoya disease 2).


    A retrospective chart review of all patients undergoing laparoscopic omental cerebral transposition for moyamoya disease between 2011 and 2014 was performed. Clinical indication, surgical technique, operative times, complications, and outcomes at follow-up were reviewed.

    Results: A total of 7 children underwent the procedure. The general surgery team performed laparoscopic omental mobilization, extraperitonealization, and subcutaneous tunneling, while the neurosurgical team performed craniotomy and cerebral application of the graft. The patients were followed postoperatively with clinic visits and angiography. There was one intraoperative complication (colon injury) and one postoperative complication (intermittent omental hernia at fascial defect for pedicle). All patients had partial to complete symptomatic resolution and demonstrated adequate intracranial revascularization on angiography.

    Conclusion: Laparoscopic omental pedicle flap mobilization and subcutaneous transposition is feasible in children who require salvage cerebral revascularization for moyamoya disease. The procedure should be considered for other conditions requiring extraperitoneal revascularization 3).


    refined a laparoscopic method of harvesting an omental flap that preserves its gastroepiploic arterial supply.

    Methods: The pedicled omentum can be lengthened as needed by dividing it between the vascular arcades. It is transposed to the brain via skip incisions. The flap can be trimmed or stretched to cover ischemic areas of the brain. The cranial exposure is performed in parallel with pediatric surgeons. We performed this technique in 3 pediatric patients with moyamoya disease (aged 5-12 years) with previous superficial temporal artery to middle cerebral artery bypasses and progressive ischemic symptoms. In 1 patient, we transposed omentum to both hemispheres.

    Results: Blood loss ranged from 75 to 250 mL. After surgery, patients immediately tolerated a diet and were discharged in 3 to 5 days. The ischemic symptoms of all 3 children resolved within 3 months postoperatively. Magnetic resonance imaging at 1 year showed improved perfusion and no new infarcts. Angiography showed excellent revascularization of targeted areas and patency of the donor gastroepiploic artery.

    Conclusion: Laparoscopic omental harvest for cranial-omental transposition can be performed efficiently and safely. Patients with moyamoya disease appear to tolerate this technique much better than laparotomy. With this method, we can achieve excellent angiographic revascularization and resolution of ischemic symptoms 4).


    Ohtaki et al. describe the long-term follow-up results for intellectual outcome and performance status and make an evaluation of regional cerebral hemodynamics after extensive omental transplantation spread over both frontal lobes performed as the initial management. In the past 10 years, 10 moyamoya patients less than 12 years of age consecutively underwent omental transplantation. The omental flap was spread over not only the symptomatic hemisphere but also the contralateral frontal lobe after a large craniotomy. Superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis was accomplished simultaneously. On the contralateral hemisphere, STA-MCA anastomosis combined with encephalomyosynangiosis was subsequently performed. The clinical observation period averaged 6.7 years (ranging from 1.9 to 9.2 years). Apart from 2 patients in whom severe mental retardation had been disclosed pre-operatively, full-scale intelligence quotient scores have been maintained at over 90, that is, within the normal intellectual range. With respect to quality of life (QOL), these 8 patients have been leading normal daily lives since the operation. The focal decrease in CBF observed in the frontal lobe pre-operatively in 7 cases had disappeared after surgical treatment. In these patients, serial post-operative MR angiography revealed developed omental vessels and STAs. Deterioration of intellectual functions and QOL as well as cerebral ischaemic events in paediatric moyamoya patients can be prevented by extensive omental transplantation spread over both frontal lobes combined with STA-MCA anastomosis 5)


    Ten patients with ischemic cerebrovascular disease including three with adult moyamoya disease underwent this procedure (omental flap on eight sides and muscle flap on five sides). The muscle used for the flap was the serratus anterior muscle on two sides and the shaved latissimus dorsi muscle on three sides. Angiography and cerebral blood flow studies were performed in all patients preoperatively and postoperatively. All patients demonstrated severely impaired cerebrovascular reserve capacity due to occlusive disease.

    There was one patient each with perioperative death and intracranial infection following omental flap loss, and two patients had perioperative strokes. The average follow-up period was 23.2 months. Of the nine surviving patients, all eight except for the one with flap loss had good outcome with complete resolution of neurologic episodes 6).


    1)

    Salimi-Jazi F, Wood LSY, Jones RE, Chandler J, Rafeeqi T, Dutta S, Steinberg G, Bruzoni M. Ten-year experience with laparoscopic pedicled omental flap for cerebral revascularization in patients with Moyamoya disease. J Pediatr Surg. 2022 Nov;57(11):710-715. doi: 10.1016/j.jpedsurg.2022.01.023. Epub 2022 Jan 31. Erratum in: J Pediatr Surg. 2023 Jul 25;: PMID: 35197196.
    2)

    Schumm M, Simon K, Sacho R, Gould JC. Successful Laparoscopic Harvesting of Omental Pedicle Flap for Salvage Cerebral Revascularization in 2 Adults With Moyamoya Disease: Technique and Lessons Learned. Surg Laparosc Endosc Percutan Tech. 2017 Oct;27(5):e111-e115. doi: 10.1097/SLE.0000000000000448. PMID: 28708772.
    3)

    Bruzoni M, Steinberg GK, Dutta S. Laparoscopic harvesting of omental pedicle flap for cerebral revascularization in children with moyamoya disease. J Pediatr Surg. 2016 Apr;51(4):592-7. doi: 10.1016/j.jpedsurg.2015.10.048. Epub 2015 Oct 19. PMID: 26611331.
    4)

    Navarro R, Chao K, Gooderham PA, Bruzoni M, Dutta S, Steinberg GK. Less invasive pedicled omental-cranial transposition in pediatric patients with moyamoya disease and failed prior revascularization. Neurosurgery. 2014 Mar;10 Suppl 1:1-14. doi: 10.1227/NEU.0000000000000119. PMID: 23921707.
    5)

    Ohtaki M, Uede T, Morimoto S, Nonaka T, Tanabe S, Hashi K. Intellectual functions and regional cerebral haemodynamics after extensive omental transplantation spread over both frontal lobes in childhood moyamoya disease. Acta Neurochir (Wien). 1998;140(10):1043-53; discussion 1052-3. doi: 10.1007/s007010050213. PMID: 9856248.
    6)

    Yoshioka N, Tominaga S, Suzuki Y, Yamazato K, Hirano S, Nonaka K, Inui T, Matuoka N. Cerebral revascularization using omentum and muscle free flap for ischemic cerebrovascular disease. Surg Neurol. 1998 Jan;49(1):58-65; discussion 65-6. doi: 10.1016/s0090-3019(97)00122-5. PMID: 9428896.

Glioblastoma prognostic markers

Glioblastoma prognostic markers


Glioblastoma (GBM) is an aggressive form of brain cancer, and predicting patient outcomes is a complex task. Prognostic markers are factors or characteristics that can help healthcare professionals estimate a patient’s likely disease course and survival. In the context of glioblastoma, several prognostic markers have been studied. Here are some of them:

Age: Increasing age is a well-established negative prognostic marker in glioblastoma. Older patients often have poorer outcomes.

Karnofsky Performance Score (KPS): This is a measure of a patient’s functional impairment and general well-being. A lower KPS score is associated with poorer prognosis.

Extent of Surgical Resection: The degree to which the tumor can be surgically removed is a significant prognostic factor. More extensive resection is associated with better outcomes.

O6-methylguanine-DNA Methyltransferase (MGMT) Methylation: Methylation of the MGMT gene promoter is associated with better responses to chemotherapy and improved survival.

Corticosteroid Use: The use of corticosteroids is associated with poor prognosis in glioblastoma patients.

Density of White Matter Tracts: Recent research has suggested that the density of white matter tracts in the brain near the tumor may be a prognostic marker. Lower tract density may indicate longer survival.

STAT5b: STAT5b activation is associated with poorer survival in glioblastoma patients.

SPTSSA Expression: SPTSSA expression may serve as a prognostic biomarker for glioma patients.

Lymphopenia: Baseline lymphopenia (a low lymphocyte count) is associated with worse overall survival in elderly glioblastoma patients.

c-Met and VEGFR2: Overexpression of c-Met and VEGFR2 may predict poorer responses to anti-angiogenic therapies in glioblastoma.

SII (Systemic Immune-Inflammation Index) and AGR (Albumin-to-Globulin Ratio): High SII and low AGR values are promising prognostic markers for identifying high-grade glioma (HGG) patients with poor prognoses.

ALK (Anaplastic Lymphoma Kinase): The role of ALK as a prognostic marker in glioblastoma is not well-established and remains controversial.

ATP-Binding Cassette Transporters: The activity of ATP-binding cassette transporters may impact prognosis by reducing drug penetration into tumor cells, but their use as isolated prognostic markers is not supported.

Tumor Geometry: Tumor shape and geometric heterogeneity can be used as prognostic markers. Patients with tumors exhibiting certain geometric characteristics may have better prognoses.

Neurologic Status: A proposed neurologic index may help predict poor outcomes in glioblastoma patients receiving tumor resection.

It’s important to note that glioblastoma is a complex and heterogeneous disease, and multiple factors can influence patient outcomes. Prognostic markers are used in combination to provide a more accurate prediction of prognosis. Additionally, ongoing research continues to uncover new markers and refine our understanding of glioblastoma prognosis.


Prognostic markers in glioblastoma are complex. In addition to previously recognized prognostic variables such as age and Karnofsky performance score, tumor size, total resection and proliferative index were identified as predictors of survival in a series of patients with glioblastoma multiforme 1).

Many reports on glioblastoma multiforme discuss the prognostic impact of anatomical features such as cysts, necrotic changes, extent of edema or subependymal spread of tumor cells.

The most consistent and well-described clinical prognostic factors associated with poor survival include: increasing age, poor performance status (PS), low degree of surgical resection of the tumor, and the use of corticosteroid2) 3) 4) 5)


Salvalaggio et al. examined two Groups of Patients: The first group, called the “discovery cohort,” included 112 patients from Italy who had surgery between February 2015 and November 2020. The second group, known as the “replicative cohort,” included 70 patients from Germany who had surgery between September 2012 and November 2015.

What They Measured: The researchers were interested in something called “white matter tracts” in the patients’ brains. They measured how dense or crowded these tracts were in the area where the GBM was located.

Main Findings:

In the first group (discovery cohort), they found that the density of these white matter tracts was related to how long patients lived after surgery. When the tracts were less dense, patients tended to live longer.

This relationship between white matter tract density and survival was stronger and more consistent compared to other factors that are commonly used to predict how GBM patients will do, like age, performance status, a specific type of DNA change (O6-methylguanine-DNA methyltransferase methylation), and how much of the tumor was removed during surgery. They confirmed these findings in the second group (replicative cohort), which makes the results more reliable. Using the density of white matter tracts, they were able to predict whether a patient would have a higher or lower chance of surviving for at least 18 or 24 months after surgery with a high level of accuracy. Conclusion: This study suggests that the density of white matter tracts in the area around the GBM may be a useful predictor of how long patients with GBM will live after surgery. It could be valuable in clinical trials and medical practice to help doctors make decisions about treatment and prognosis.

In simple terms, the study found that the structure of certain brain pathways is related to how long patients with brain cancer live after surgery. This could be a helpful tool for doctors when treating these patients. 6).

STAT5b is frequently activated in Glioblastoma and correlates inversely with patient survival. It does not contribute to the growth and resistance of these tumors and is thus rather a potential prognostic marker than a therapeutic target in these tumors 7).

SPTSSA expression might be used as a prognostic biomarker for glioma and a potential target for novel glioma therapy 8)

Baseline lymphopenia is associated with worse OS, which may be considered a prognostic biomarker for elderly glioblastoma outcome patients 9)

c-Met and VEGFR2 overexpression have a role in the development of glioblastoma early resistance and might predict poorer responses to anti-angiogenic therapies. 10)


Liang et al., demonstrated that high SII and low AGR values may serve as promising prognostic markers to identify HGG patients with poor prognosis 11).

Data on the prognostic role of ALK in Glioblastoma are very limited and remain controversial 12) 13) 14).

The activity of ATP-binding cassette transporters severely reduces the amount of therapeutics that penetrates the tumor cells. Roy et al. hypothesized that ABC transporter expression could correlate with survival surrogates. They assessed the expression of four commonly expressed ABC transporters in GBM samples and investigated if mRNA levels could serve as a prognostic biomarker.

The expression of the four ABC transporters evaluated would not be suitable prognostic biomarkers. They believe that when estimating prognosis, the plethora of mechanisms implicated in chemoresistance should be analyzed as a multi-facetted entity rather than isolated units 15).

Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These imaging biomarkers have a strong individual and combined prognostic value for Glioblastoma patients 16) 17).


Multi-channel MR image derived texture features, tumor shape, and volumetric features, and patient age were obtained for 163 Glioblastoma patients. In order to assess the impact of tumor shape features on OS prediction, two feature sets, with and without tumor shape features, were created. For the feature set with tumor shape features, the mean prediction error (MPE) was 14.6 days and its 95% confidence interval (CI) was 195.8 days. For the feature set excluding shape features, the MPE was 17.1 days and its 95% CI was observed to be 212.7 days. The coefficient of determination (R2) value obtained for the feature set with shape features was 0.92, while it was 0.90 for the feature set excluding shape features. Although marginal, the inclusion of shape features improves OS prediction in Glioblastoma patients. The proposed OS prediction method using regression provides good accuracy and overcomes the limitations of Glioblastoma OS classification, like choosing data-derived or pre-decided thresholds to define the OS groups. Graphical abstract Two feature sets: with and without tumor shape features were extracted from T1-weighted contrast-enhanced, T2-weighted and FLAIR MRI. These feature sets were analyzed using the Mean Prediction Error (MPE) and its 95% Confidence Interval (CI) obtained from the Bland-Altman plot, along with the coefficient of determination (R2) value to assess the impact of tumor shape features on overall survival prediction of glioblastoma multiforme patients 18).

Neurologic status is one of the major prognostic factors; however, no consensus exists on a clinical index for predicting patient outcomes.

One proposed neurologic index enables significant identification of glioblastoma patients receiving tumor resection with poor outcomes, independent of other common prognostic factors. Using the index provides a preoperative predictor of prognosis in glioblastoma patients receiving tumor resection 19).

What are prognostic markers used for in medicine? a) To diagnose diseases b) To predict the likely outcome of a disease in a patient c) To treat diseases d) To prevent diseases

In glioblastoma, which of the following factors were identified as predictors of survival in addition to age and performance score? a) Blood pressure and cholesterol levels b) Tumor size and total resection c) DNA mutations and tumor grade d) Blood type and genetic markers

What did Salvalaggio et al. measure in the brains of glioblastoma patients to assess prognosis? a) Blood flow b) White matter tract density c) Tumor size d) Brain volume

What was the main finding of the study conducted by Salvalaggio et al. regarding white matter tracts? a) White matter tract density was unrelated to patient survival. b) Patients with denser white matter tracts tended to live longer. c) White matter tracts were unrelated to tumor location. d) White matter tracts were unrelated to age.

Which of the following is NOT mentioned as a clinical prognostic factor associated with poor survival in glioblastoma? a) Increasing age b) Poor performance status (PS) c) Extent of surgical resection d) Use of corticosteroids

What is the potential role of STAT5b in glioblastoma? a) It contributes to tumor growth and resistance. b) It is a therapeutic target for glioblastoma. c) It is a prognostic marker. d) It has no role in glioblastoma.

What is SPTSSA expression potentially used for in glioma? a) Diagnosis b) Prognostic marker c) Treatment d) Disease prevention

What is lymphopenia considered as in elderly glioblastoma outcome patients? a) A marker of good prognosis b) A marker of disease progression c) A prognostic biomarker for poor outcome d) A diagnostic marker

What do c-Met and VEGFR2 overexpression predict in glioblastoma? a) Positive response to anti-angiogenic therapies b) Increased tumor size c) Resistance to chemotherapy d) No impact on patient outcomes

Which statement about ALK as a prognostic marker in glioblastoma is true? a) It is a well-established prognostic marker. b) Data on its prognostic role are limited and controversial. c) It is a therapeutic target for glioblastoma. d) It is not associated with patient survival.


What are prognostic markers used for in medicine? Answer: b) To predict the likely outcome of a disease in a patient

In glioblastoma, which of the following factors were identified as predictors of survival in addition to age and performance score? Answer: b) Tumor size and total resection

What did Salvalaggio et al. measure in the brains of glioblastoma patients to assess prognosis? Answer: b) White matter tract density

What was the main finding of the study conducted by Salvalaggio et al. regarding white matter tracts? Answer: b) Patients with denser white matter tracts tended to live longer.

Which of the following is NOT mentioned as a clinical prognostic factor associated with poor survival in glioblastoma? Answer: d) Use of corticosteroids

What is the potential role of STAT5b in glioblastoma? Answer: c) It is a prognostic marker.

What is SPTSSA expression potentially used for in glioma? Answer: b) Prognostic marker

What is lymphopenia considered as in elderly glioblastoma outcome patients? Answer: c) A prognostic biomarker for poor outcome

What do c-Met and VEGFR2 overexpression predict in glioblastoma? Answer: a) Positive response to anti-angiogenic therapies

Which statement about ALK as a prognostic marker in glioblastoma is true? Answer: b) Data on its prognostic role are limited and controversial.



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Gittleman H, Lim D, Kattan MW, Chakravarti A, Gilbert MR, Lassman AB, et al. An independently validated nomogram for individualized estimation of survival among patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825. Neuro Oncol (2017) 19(5):669–77. doi: 10.1093/neuonc/now208
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Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG, et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol (2008) 9(1):29–38. doi: 10.1016/S1470-2045(07)70384-4
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Li H, He Y, Huang L, Luo H, Zhu X. The Nomogram Model Predicting Overall Survival and Guiding Clinical Decision in Patients With Glioblastoma Based on the SEER Database. Front Oncol (2020) 10:1051:1051. doi: 10.3389/fonc.2020.01051
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Dubois N, Berendsen S, Tan K, Schoysmans L, Spliet W, Seute T, Bours V, Robe PA. STAT5b is a marker of poor prognosis, rather than a therapeutic target in glioblastomas. Int J Oncol. 2022 Oct;61(4):124. doi: 10.3892/ijo.2022.5414. Epub 2022 Sep 7. PMID: 36069226.
8)

Wang Z, Ge X, Shi J, Lu B, Zhang X, Huang J. SPTSSA Is a Prognostic Marker for Glioblastoma Associated with Tumor-Infiltrating Immune Cells and Oxidative Stress. Oxid Med Cell Longev. 2022 Aug 24;2022:6711085. doi: 10.1155/2022/6711085. PMID: 36062185; PMCID: PMC9434331.
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Song AJ, Ding K, Alnahhas I, Laperriere NJ, Perry J, Mason WP, Winch C, O’Callaghan CJ, Menten JJ, Brandes AA, Phillips C, Fay MF, Nishikawa R, Osoba D, Cairncross JG, Roa W, Wick W, Shi W. Impact of lymphopenia on survival for elderly patients with glioblastoma: A secondary analysis of the CCTG CE.6 (EORTC 26062-22061, TROG03.01) randomized clinical trial. Neurooncol Adv. 2021 Oct 15;3(1):vdab153. doi: 10.1093/noajnl/vdab153. Erratum in: Neurooncol Adv. 2022 Jan 27;4(1):vdac011. PMID: 34765975; PMCID: PMC8577525.
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Carvalho B, Lopes JM, Silva R, Peixoto J, Leitão D, Soares P, Fernandes AC, Linhares P, Vaz R, Lima J. The role of c-Met and VEGFR2 in glioblastoma resistance to bevacizumab. Sci Rep. 2021 Mar 16;11(1):6067. doi: 10.1038/s41598-021-85385-1. PMID: 33727583.
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Liang R, Li J, Tang X, Liu Y. The prognostic role of preoperative systemic immune-inflammation index and albumin/globulin ratio in patients with newly diagnosed high-grade glioma. Clin Neurol Neurosurg. 2019 Jun 24;184:105397. doi: 10.1016/j.clineuro.2019.105397. [Epub ahead of print] PubMed PMID: 31306893.
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Elsers D, Temerik DF, Attia AM, Hadia A, Hussien MT. Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations. J Pathol Transl Med. 2021;55:212–224.
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Karagkounis G, Stranjalis G, Argyrakos T, et al. Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome. J Clin Pathol. 2017;70:593–9.
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Franceschi E, De Biase D, Di Nunno V, et al. The clinical and prognostic role of ALK in glioblastoma. Pathol Res Pract. 2021;221:153447.
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Roy LO, Lemelin M, Blanchette M, Poirier MB, Aldakhil S, Fortin D. Expression of ABCB1, ABCC1 and 3 and ABCG2 in glioblastoma and their relevance in relation to clinical survival surrogates. J Neurooncol. 2022 Nov 7. doi: 10.1007/s11060-022-04179-1. Epub ahead of print. PMID: 36342588.
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Pérez-Beteta J, Martínez-González A, Molina D, Amo-Salas M, Luque B, Arregui E, Calvo M, Borrás JM, López C, Claramonte M, Barcia JA, Iglesias L, Avecillas J, Albillo D, Navarro M, Villanueva JM, Paniagua JC, Martino J, Velásquez C, Asenjo B, Benavides M, Herruzo I, Delgado MD, Del Valle A, Falkov A, Schucht P, Arana E, Pérez-Romasanta L, Pérez-García VM. Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study. Eur Radiol. 2017 Mar;27(3):1096-1104. doi: 10.1007/s00330-016-4453-9. PubMed PMID: 27329522.
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DNA methylation in intracranial aneurysm pathogenesis

DNA methylation in intracranial aneurysm pathogenesis

Epigenetic modifications, including DNA methylation, are thought to play a role in the intracranial aneurysm pathogenesis. Here’s how:

Gene Expression Regulation: DNA methylation can regulate the expression of genes involved in various aspects of vascular biology, including inflammation, vascular smooth muscle cell function, and extracellular matrix remodeling. Aberrant DNA methylation patterns in these genes may contribute to the weakening of blood vessel walls and the development of aneurysms.

Inflammation and Immune Response: Chronic inflammation and immune system activation are associated with IA development. DNA methylation can influence the expression of genes involved in the regulation of immune responses. Altered DNA methylation patterns in immune-related genes may contribute to the chronic inflammation observed in IA pathogenesis.

Vascular Smooth Muscle Cell Dysfunction: Proper functioning of vascular smooth muscle cells (VSMCs) is essential for maintaining blood vessel integrity. Dysregulated DNA methylation in genes related to VSMC contractility and function may lead to VSMC dysfunction and contribute to aneurysm formation.

Extracellular Matrix Remodeling: The extracellular matrix (ECM) provides structural support to blood vessel walls. DNA methylation can affect the expression of genes involved in ECM remodeling and integrity. Changes in DNA methylation patterns may disrupt the balance between ECM synthesis and degradation, making blood vessels more susceptible to aneurysm formation.

Risk Factors and Environmental Influences: Environmental factors, such as smoking, hypertension, and inflammation, are known risk factors for IAs. These factors can influence DNA methylation patterns in genes related to vascular health, further contributing to IA development in susceptible individuals.

Research in this area is ongoing, and studies are actively exploring the epigenetic mechanisms, including DNA methylation, that underlie IA pathogenesis. Identifying specific DNA methylation changes associated with IAs may lead to the development of novel diagnostic markers or therapeutic targets for this condition. However, it’s important to note that IA development is likely influenced by a complex interplay of genetic, epigenetic, and environmental factors, and more research is needed to fully understand the precise mechanisms involved.


Maimaiti et al. employed a comprehensive bioinformatics investigation of DNA methylation in IA, utilizing a transcriptomics-based methodology that encompassed 100 machine learning algorithms, genome-wide association study (GWAS), Mendelian randomization (MR), and summary-data-based Mendelian randomization (SMR). The sophisticated analytical strategy allowed for a systematic assessment of differentially methylated genes and their implications on the onset, progression, and rupture of IA.

They identified DNA methylation-related genes (MRGs) and associated molecular pathways, and the MR and SMR analyses provided evidence for potential causal links between the observed DNA methylation events and IA predisposition.

These insights not only augment our understanding of the molecular underpinnings of IA but also underscore potential novel biomarkers and therapeutic avenues. Although the study faces inherent limitations and hurdles, it represents a groundbreaking initiative in deciphering the intricate relationship between genetic, epigenetic, and environmental factors implicated in IA pathogenesis 1).

The IL6/JAK/STAT signaling pathway (ISP) is significant positively correlated with intracranial aneurysm onset. The biological function of the ISP is positively correlated with that of the estrogen response pathway (ERP), and is significantly associated with immune cells activities. CSF2RB, FAS, IL6, PTPN1, STAT2, TGFB1 of the ISP gene set and ALDH3A2, COX6C, IGSF1, KRT18, MICB, NPY1R of the ERP gene set were proved to be the characteristic genes. The STAT2 gene can be the potential biomarker of IA onset. The immune score of IA samples was significantly higher than the controls. The STAT2 gene expression is associated with infiltration of immune cells. The WGCNA results were consistent with our finds. Acetaminophen can be a potential therapeutic drug for IA targeting STAT2

They identified that the ISP was one of the most significant positively correlated pathways in IA onset, and it was activated in this process concordant with the ERP and immune responses. Except for beneficial effects, complex and multiple roles of estrogen may be involved in IA formation. STAT2 could be a potential biomarker and a promising therapeutic target of IA pathogenesis 2).

Saccular intracranial aneurysm rupture leads to subarachnoid hemorrhage and is preceded by chronic inflammation and atherosclerotic changes of the Saccular intracranial aneurysm wall. Increased lymphangiogenesis has been detected in atherosclerotic extracranial arteries and in abdominal aortic aneurysms, but the presence of lymphatic vessels in saccular intracranial aneurysm (sIAs) has remained unexplored. Huuska et al. studied the presence of lymphatic vessels in 36 intraoperatively resected sIAs (16 unruptured and 20 ruptured), using immunohistochemical and immunofluorescence stainings for Lymphatic endothelial cells (LEC)markers. Of these LEC-markers, both extracellular and intracellular LYVE1podoplaninVEGFR-3, and Prox1-positive stainings were detected in 83%, 94%, 100%, and 72% of the 36 sIA walls, respectively. Lymphatic vessels were identified as ring-shaped structures positive for one or more of the LEC markers. Of the sIAs, 78% contained lymphatic vessels positive for at least one LEC marker. The presence of LECs and lymphatic vessels were associated with the number of CD68+ and CD163+ cells in the sIA walls, and with the expression of inflammation indicators such as serum amyloid A, myeloperoxidase, and cyclo-oxygenase 2, with the presence of a thrombus, and with the sIA wall rupture. Large areas of VEGFR-3 and α-smooth muscle actin (αSMA) double-positive cells were detected in medial parts of the sIA walls. Also, a few podoplanin and αSMA double-positive cells were discovered. In addition, LYVE-1 and CD68 double-positive cells were detected in the sIA walls and in the thrombus revealing that certain CD68+ macrophages are capable of expressing LEC markers. This study demonstrates for the first time the presence of lymphatic vessels in human sIA walls. Further studies are needed to understand the role of lymphatic vessels in the saccular intracranial aneurysm pathogenesis 3).

Dysfunction of vascular smooth muscle cells (VSMCs) plays a critical role in the intracranial aneurysm pathogenesis (IA). Circular RNAs (circRNAs) have been implicated by reducing microRNA (miRNA) activity. Qin et al. investigated the precise roles of circRNA ADP ribosylation factor interacting protein 2 (circ-ARFIP2, circ_0021001) in VSMC dysfunction. The levels of circ-ARFIP2, miR-338-3p and kinase insert domain receptor (KDR) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease (RNase) R and subcellular fractionation assays were used to assess the stability and localization of circ-ARFIP2, respectively. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell invasion was measured by transwell assay. Cell proliferation was gauged by 5-Ethynyl-2′-Deoxyuridine (EdU) assay. Cell migration was evaluated by transwell and wound-healing assays. Targeted correlations among circ-ARFIP2, miR-338-3p and KDR were validated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Circ-ARFIP2 and KDR were underexpressed and miR-338-3p was overexpressed in the arterial wall tissues of IA patients. Overexpression of circ-ARFIP2 in human umbilical artery smooth muscle cells (HUASMCs) showed a significant promotion in cell proliferation, migration and invasion. Mechanistically, circ-ARFIP2 targeted miR-338-3p, and circ-ARFIP2 regulated cell behaviors by miR-338-3p. KDR was a direct and functional target of miR-338-3p. Moreover, KDR was a downstream effector of circ-ARFIP2 function. Circ-ARFIP2 regulated KDR expression by targeting miR-338-3p.The findings demonstrated that the increased level of circ-ARFIP2 enhanced HUASMC proliferation, migration and invasion at least in part by the miR-338-3p/KDR axis 4).

Pathogenic inflammation contributes to aneurysm formation by mediating the destruction of the endothelium and the extracellular matrix and promoting the pathogenic proliferation of smooth muscle cells. In mouse models, tolerance-inducing T regulatory (Treg) cells could significantly reduce the incidence and severity of aneurysms. Hence, it should be investigated why in human intracranial aneurysm (IA) patients, Treg cells failed to provide protection against aneurysm formation. In this study, the frequency and function of Treg cells in IA patients were examined. The frequency of Foxp3+ Treg cells was significantly lower in IA patients than in healthy controls. This downregulation was only specific to the Treg subset of CD4+ T cells, as the frequency of total CD4+ T cell was increased in IA patients. Subsequently, we found that the expressions of Treg-associated molecules, including Foxp3, CTLA-4, TGF-β, and IL-10, were significantly lower in Foxp3+ Treg cells from IA patients than in Foxp3+ Treg cells from healthy controls. In both healthy controls and IA patients, Foxp3+ Treg cells were distinguished into a more potent Tim-3+ subset and a less potent Tim-3- subset. The Tim-3+ subset of Foxp3+ Treg cells was significantly reduced in IA patients. Signaling via IL-2, IL-7, IL-15 and IL-21 was shown to promote Tim-3 upregulation in CD4+ and CD8+ T cells. Interestingly, we found that Tim-3 could be upregulated in Treg cells via the same mechanism, but compared to the Treg cells from healthy controls, the Treg cells from IA patients presented defects in Tim-3 upregulation upon cytokine stimulation. Together, our results demonstrated that Foxp3+ Treg cells in IA patients presented reduced function, which was associated with a defect in Tim-3 upregulation 5).

here’s a multiple-choice test based on the information provided about epigenetic modifications and their role in intracranial aneurysm (IA) pathogenesis:

What is the primary role of DNA methylation in gene expression regulation?

a) Activating gene expression b) Repressing gene expression c) Altering DNA sequences d) Enhancing protein translation

In the context of IA pathogenesis, what role does DNA methylation play in vascular biology?

a) Promoting blood vessel dilation b) Reducing inflammation c) Regulating immune responses d) Weakening blood vessel walls

Which of the following is NOT a component of the extracellular matrix (ECM)?

a) Collagen b) Elastin c) Fibronectin d) Lymphocytes

How do matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) contribute to ECM remodeling?

a) MMPs inhibit ECM degradation, while TIMPs promote it. b) Both MMPs and TIMPs promote ECM degradation. c) MMPs promote ECM degradation, while TIMPs inhibit it. d) MMPs and TIMPs have no role in ECM remodeling.

What type of cells are responsible for synthesizing and secreting ECM components?

a) Neurons b) Vascular smooth muscle cells c) Red blood cells d) Epithelial cells

How does DNA methylation relate to the risk factors and environmental influences associated with IA development?

a) It decreases the risk of IA. b) It has no impact on IA risk factors. c) It can be influenced by environmental factors and may contribute to IA development. d) It is solely determined by genetic factors.

What is the primary role of circular RNAs (circRNAs) in the context of vascular smooth muscle cell (VSMC) dysfunction in IA?

a) Promoting VSMC proliferation b) Suppressing VSMC migration c) Inhibiting DNA methylation d) Regulating immune responses

What is the significance of the IL6/JAK/STAT signaling pathway in IA onset?

a) It has no relevance to IA. b) It negatively regulates immune responses. c) It is positively correlated with IA onset and influences immune cell activities. d) It directly causes IA formation.

What is the main function of T regulatory (Treg) cells in the context of IA?

a) Promoting inflammation b) Reducing the severity of IA c) Causing aneurysm formation d) Increasing the frequency of IA

How do Tim-3+ subsets of Foxp3+ Treg cells differ between IA patients and healthy controls?

a) They are more potent in IA patients. b) They are less potent in IA patients. c) They are equally potent in both groups. d) They have no impact on IA.

Answers:

b) Repressing gene expression d) Weakening blood vessel walls d) Lymphocytes c) MMPs promote ECM degradation, while TIMPs inhibit it. b) Vascular smooth muscle cells c) It can be influenced by environmental factors and may contribute to IA development. a) Promoting VSMC proliferation c) It is positively correlated with IA onset and influences immune cell activities. b) Reducing the severity of IA b) They are less potent in IA patients


1)

Maimaiti A, Turhon M, Abulaiti A, Dilixiati Y, Zhang F, Axieer A, Kadeer K, Zhang Y, Maimaitili A, Yang X. DNA methylation regulator-mediated modification patterns and risk of intracranial aneurysm: a multi-omics and epigenome-wide association study integrating machine learning, Mendelian randomization, eQTL and mQTL data. J Transl Med. 2023 Sep 23;21(1):660. doi: 10.1186/s12967-023-04512-w. PMID: 37742034.
2)

Wu A, Zhao C, Mou S, Li S, Cui X, Zhang R. Integrated analysis identifies the IL6/JAK/STAT signaling pathway and the estrogen response pathway associated with the pathogenesis of intracranial aneurysms. Front Immunol. 2022 Nov 14;13:1046765. doi: 10.3389/fimmu.2022.1046765. PMID: 36451838; PMCID: PMC9702531.
3)

Huuska N, Netti E, Lehti S, Kovanen PT, Niemelä M, Tulamo R. Lymphatic vessels are present in human saccular intracranial aneurysms. Acta Neuropathol Commun. 2022 Sep 5;10(1):130. doi: 10.1186/s40478-022-01430-8. PMID: 36064651.
4)

Qin K, Tian G, Zhou D, Chen G. Circular RNA circ-ARFIP2 regulates proliferation, migration and invasion in human vascular smooth muscle cells via miR-338-3p-dependent modulation of KDR. Metab Brain Dis. 2021 Apr 10. doi: 10.1007/s11011-021-00726-3. Epub ahead of print. PMID: 33837886.
5)

Zhang HF, Liang GB, Zhao MG, Zhao GF, Luo YH. Patients with intracranial aneurysms presented defects in regulatory T cells, which were associated with impairment in Tim-3 upregulation. Int Immunopharmacol. 2018 Sep 19;64:350-355. doi: 10.1016/j.intimp.2018.09.020. [Epub ahead of print] PubMed PMID: 30243071.

Thiopental

Thiopental

Thiopental (Pentothal®)


Thiopental administration has been described as an effective method to prevent postoperative neurological deficits in several animal studies 1) 2) 3) 4) 5)

Here are some key points about the use of thiopental in neurosurgery:

Induction of Anesthesia: Thiopental is often used as an induction agent to rapidly induce anesthesia in patients undergoing neurosurgical procedures. Its rapid onset of action makes it suitable for this purpose.

Sedation and Amnesia: Thiopental induces a state of sedation, amnesia, and unconsciousness, which is important for ensuring that patients do not experience pain or awareness during surgery.

Short Duration: One of the advantages of thiopental is its short duration of action. This allows for precise control of anesthesia depth and a quick recovery once the drug is discontinued.

Neuroprotective Properties: Thiopental has been investigated for its potential neuroprotective properties in the context of neurosurgery. It may help reduce the metabolic demands of the brain during surgery, which could be beneficial in cases where brain tissue needs to be protected.

Control of Intracranial Pressure (ICP): Thiopental can temporarily lower intracranial pressure (ICP), which can be important in neurosurgical procedures involving brain tumors or traumatic brain injury. By reducing ICP, it may provide a safer surgical environment.

Barbiturate Coma: In some cases of severe traumatic brain injury or refractory intracranial hypertension, thiopental has been used to induce a controlled barbiturate coma. This coma state is maintained for a specific duration to protect the brain from further damage and reduce ICP.

Administration: Thiopental is administered intravenously, typically as a rapid bolus injection. The dosage and administration rate are carefully controlled by an anesthesiologist to achieve the desired level of anesthesia.

Side Effects: Like all anesthetic drugs, thiopental can have side effects, including respiratory depression, hypotension (low blood pressure), and a risk of allergic reactions. These side effects are closely monitored during surgery.

Availability: The availability of thiopental may vary by region, and its use may be subject to regulatory restrictions. In some places, it has become less commonly used due to concerns about the misuse and availability of lethal injection

May be useful when a rapidly acting barbiturate is needed (e.g. intra-op) or when large doses of pentobarbital are not available. One of many protocols is as follows (note: thiopental has not been as well studied for this indication, but is theoretically similar to pentobarbital):

1. Loading dose: thiopental 5 mg/kg (range: 3–5) IV over 10 minutes → transient burst suppression (< 10 minutes) and blood thiopental levels of 10–30 mcg/ml. Higher doses (≈ 35 mg/kg) have been used in the absence of hypothermia to produce longer-duration burst suppression for cardiopulmonary bypass

2. Follow with continuous infusion of 5 mg/kg/hr (range: 3–5) for 24 hours

3. may need to rebolus with 2.5 mg/kg as needed for ICP control

4. After 24 hours, fat stores become saturated, reduce infusion to 2.5 mg/kg/hr

5. titrate to control ICP or use EEG to monitor for electrocerebral silence

6. “therapeutic” serum level: 6–8.5 mg/dl


Chemically, propofol is not related to barbiturates and has largely replaced sodium thiopental (Pentothal) for induction of anesthesia because recovery from propofol is more rapid and “clear” when compared with thiopental. Propofol is not considered an analgesic, so opioids such as fentanyl may be combined with propofol to alleviate pain.


Thiopental and decompressive craniectomy are important integrated last-tier treatment options in aneurysmal subarachnoid hemorrhage, but careful patient selection is needed due to the risk of saving many patients a state of suffering 6).


A study showed that thiopental was associated with a lower risk of neurological complications after clipping of Unruptured Intracranial Aneurysm 7).

What is the primary purpose of using Thiopental in neurosurgery? a) Pain relief b) Rapid induction of anesthesia c) Prolonged sedation d) Reducing blood pressure

Why is Thiopental chosen for induction in neurosurgery? a) It provides prolonged anesthesia. b) It has a rapid onset of action. c) It reduces intracranial pressure. d) It is an effective analgesic.

Which of the following is NOT a characteristic of Thiopental? a) Short duration of action b) Neuroprotective properties c) Rapid bolus injection d) Long-lasting sedation

In what situations might Thiopental be used to induce a controlled barbiturate coma? a) Routine neurosurgical procedures b) Cases of severe traumatic brain injury c) During outpatient surgeries d) For postoperative pain management

How is Thiopental typically administered? a) Orally b) Intramuscularly c) Intravenously d) Subcutaneously

What is the recommended therapeutic serum level of Thiopental? a) 1-2 mg/dl b) 6-8.5 mg/dl c) 20-30 mcg/ml d) 50-60 mg/dl

Why has Propofol largely replaced Thiopental for induction of anesthesia? a) Propofol is cheaper. b) Propofol has a shorter duration of action. c) Propofol is more effective at reducing intracranial pressure. d) Propofol has a faster recovery time.

What is a potential risk associated with using Thiopental in neurosurgery? a) Rapid recovery b) Allergic reactions c) Hypertension d) Analgesia

When might Thiopental and decompressive craniectomy be considered as treatment options in aneurysmal subarachnoid hemorrhage? a) As a first-line treatment b) As a second-line treatment c) As a last-tier treatment d) Only in cases of minor bleeding

What did a study suggest about the use of Thiopental in clipping of Unruptured Intracranial Aneurysm? a) It had no impact on neurological complications. b) It increased the risk of complications. c) It was associated with a lower risk of neurological complications. d) It prolonged surgical procedures.

Answers:

b) Rapid induction of anesthesia b) It has a rapid onset of action. d) Long-lasting sedation b) Cases of severe traumatic brain injury c) Intravenously b) 6-8.5 mg/dl d) Propofol has a faster recovery time. b) Allergic reactions c) As a last-tier treatment c) It was associated with a lower risk of neurological complications.


1)

Michenfelder J.D. The Interdependency of Cerebral Functional and Metabolic Effects Following Massive Doses of Thiopental in the Dog. Anesthesiology. 1974;41:231–236. doi: 10.1097/00000542-197409000-00004.
2)

Drummond J.C., Cole D.J., Patel P.M., Reynolds L.W. Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: A comparison of the extent of cerebral injury. Neurosurgery. 1995;37:742–748. doi: 10.1227/00006123-199510000-00019.
3)

Kofke W.A., Nemoto E.M., Hossmann K.A., Taylor F., Kessler P.D., Stezoski S.W. Brain blood flow and metabolism after global ischemia and post-insult thiopental therapy in monkeys. Stroke. 1979;10:554–560. doi: 10.1161/01.STR.10.5.554.
4)

Musch T.I., Pelligrino D.A., Dempsey J.A. Effects of prolonged N2O and barbiturate anaesthesia on brain metabolism and pH in the dog. Respir. Physiol. 1980;39:121–131. doi: 10.1016/0034-5687(80)90040-7.
5)

Zarchin N., Guggenheimer-Furman E., Meilin S., Ornstein E., Mayevsky A. Thiopental induced cerebral protection during ischemia in gerbils. Brain Res. 1998;780:230–236. doi: 10.1016/S0006-8993(97)01188-8.
6)

Björk S, Hånell A, Ronne-Engström E, Stenwall A, Velle F, Lewén A, Enblad P, Svedung Wettervik T. Thiopental and decompressive craniectomy as last-tier ICP-treatments in aneurysmal subarachnoid hemorrhage: is functional recovery within reach? Neurosurg Rev. 2023 Sep 7;46(1):231. doi: 10.1007/s10143-023-02138-6. PMID: 37676578.
7)

Kim BG, Jeon YT, Han J, Bae YK, Lee SU, Ryu JH, Koo CH. The Neuroprotective Effect of Thiopental on the Postoperative Neurological Complications in Patients Undergoing Surgical Clipping of Unruptured Intracranial Aneurysm: A Retrospective Analysis. J Clin Med. 2021 Mar 12;10(6):1197. doi: 10.3390/jcm10061197. PMID: 33809302; PMCID: PMC7999640.

Antibiotics for spondylodiscitis treatment

Antibiotics for spondylodiscitis treatment

The choice of antibiotics for the treatment of spondylodiscitis depends on several factors, including the suspected or identified causative microorganism, the severity of the infection, and individual patient factors such as allergies and underlying medical conditions. Empirical antibiotic therapy may be initiated before the exact microorganism is identified based on clinical presentation and risk factors. However, once the causative organism is identified through cultures, antibiotic therapy can be adjusted accordingly. Commonly implicated bacteria in pyogenic spondylodiscitis include Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus or MRSA), Streptococcus species, and Escherichia coli.

Here are some antibiotic options commonly used for the treatment of spondylodiscitis:

Empirical Antibiotics: These antibiotics may be started before the specific microorganism is identified. Common choices include:

Intravenous (IV) antibiotics such as ceftriaxone or cefotaxime plus MRSA coverage with vancomycin or daptomycin. Broad-spectrum antibiotics like piperacillin-tazobactam or meropenem in critically ill patients with risk factors for multidrug-resistant organisms. Specific Antibiotics: Once the causative organism is identified, the antibiotics can be tailored to target that particular microorganism. Antibiotics often used for specific bacteria include:

For Staphylococcus aureus, including MRSA: Vancomycin, daptomycin, or linezolid. For Streptococcus species: Penicillin or ceftriaxone. For Escherichia coli and other Gram-negative bacteria: Ceftriaxone, cefotaxime, or fluoroquinolones.

The duration of antibiotic therapy typically ranges from 6 to 12 weeks or longer, depending on the severity of the infection, the response to treatment, and the presence of complications. Prolonged treatment is often necessary to ensure complete eradication of the infection and to prevent relapse.


The appropriate duration of parenteral antibiotic treatment in patients with pyogenic spondylodiscitis after surgical intervention could be guided by the risk factors. The duration of postoperative intravenous antibiotic therapy could be reduced to 3 weeks for patients without positive blood culture or abscess formation 2)

Intravenous to Oral Transition: In some cases, patients may be transitioned from intravenous to oral antibiotics once they show clinical improvement and are stable. This transition is based on the patient’s clinical response and the recommendations of the healthcare team.

Monitoring: Close monitoring of the patient’s clinical progress, laboratory markers of infection (such as C-reactive protein and erythrocyte sedimentation rate), and imaging studies is essential to assess treatment efficacy and identify any complications.

It’s important for patients to complete the full course of antibiotics as prescribed to prevent relapse and the development of antibiotic resistance.


A nationwide survey of empiric antibiotic treatment for pyogenic spondylodiscitis revealed a large heterogeneity in the standard of care. A combination of a broad-spectrum-β-lactam antibiotic with an additional glycopeptide antibiotic may be justified 3)



Empirical broad-spectrum antibiotic therapy is linked to increased rates of complications such as Clostridium difficile-associated diarrhea and higher healthcare costs 4), and should be reserved for patients presenting with severe sepsis once blood cultures have been taken.

Question 1: Which of the following is NOT an indication for surgical treatment in spondylodiscitis?

A) Neurologic deficits B) Sepsis C) Intraspinal empyema D) Positive blood culture

Question 2: Why might empirical antibiotic therapy be initiated before the exact microorganism is identified in spondylodiscitis?

A) To prevent antibiotic resistance B) To reduce the duration of antibiotic treatment C) To avoid potential side effects of antibiotics D) To provide immediate treatment while awaiting culture results

Question 3: Which of the following is a commonly implicated bacterium in pyogenic spondylodiscitis?

A) Candida albicans B) Escherichia coli C) Mycobacterium tuberculosis D) Streptococcus pneumoniae

Question 4: What is the typical duration of antibiotic therapy for spondylodiscitis?

A) 1-2 weeks B) 2-4 weeks C) 4-6 weeks D) 6-12 weeks or longer

Question 5: Under what circumstances can intravenous antibiotic therapy be reduced to 3 weeks after surgical intervention in spondylodiscitis?

A) Positive blood culture B) Abscess formation C) Clinical improvement D) All of the above

Question 6: When might a patient with spondylodiscitis be transitioned from intravenous to oral antibiotics?

A) Immediately upon diagnosis B) After surgical intervention C) Once blood cultures are taken D) When they show clinical improvement and are stable

Question 7: Why is close monitoring of patients with spondylodiscitis essential during treatment?

A) To assess treatment efficacy B) To prevent antibiotic resistance C) To reduce healthcare costs D) To guide surgical interventions

Question 8: What should patients do to prevent relapse and the development of antibiotic resistance during spondylodiscitis treatment?

A) Start antibiotic treatment as soon as possible B) Take antibiotics until they feel better C) Complete the full course of antibiotics as prescribed D) Reduce the antibiotic dose gradually

Question 9: In what situation might a combination of a broad-spectrum-β-lactam antibiotic with an additional glycopeptide antibiotic be justified in spondylodiscitis treatment?

A) In all cases B) When blood cultures are negative C) In patients with severe sepsis once blood cultures have been taken D) In patients with mild infection

Question 10: What is the potential drawback of starting empirical broad-spectrum antibiotic therapy in spondylodiscitis?

A) Reduced treatment efficacy B) Increased rates of Clostridium difficile-associated diarrhea C) Lower healthcare costs D) Shorter hospital stays

Answers:

D) Positive blood culture D) To provide immediate treatment while awaiting culture results B) Escherichia coli D) 6-12 weeks or longer D) All of the above D) When they show clinical improvement and are stable A) To assess treatment efficacy C) Complete the full course of antibiotics as prescribed C) In patients with severe sepsis once blood cultures have been taken B) Increased rates of Clostridium difficile-associated diarrhea


1)

Herren C, Jung N, Pishnamaz M, Breuninger M, Siewe J, Sobottke R. Spondylodiscitis: Diagnosis and Treatment Options. Dtsch Arztebl Int. 2017 Dec 25;114(51-52):875-882. doi: 10.3238/arztebl.2017.0875. PMID: 29321098; PMCID: PMC5769318.
2)

Li YD, Wong CB, Tsai TT, Lai PL, Niu CC, Chen LH, Fu TS. Appropriate duration of post-surgical intravenous antibiotic therapy for pyogenic spondylodiscitis. BMC Infect Dis. 2018 Sep 17;18(1):468. doi: 10.1186/s12879-018-3377-1. PMID: 30223785; PMCID: PMC6142394.
3)

Lang S, Walter N, Neumann C, Bärtl S, Simon M, Ehrenschwender M, Hitzenbichler F, Alt V, Rupp M. Aktuelle Praxis der empirischen Antibiotikatherapie bei Spondylodiszitis [Current practice of empiric antibiotic treatment for spondylodiscitis]. Orthopadie (Heidelb). 2022 Jul;51(7):540-546. German. doi: 10.1007/s00132-022-04240-x. Epub 2022 Apr 7. PMID: 35391543; PMCID: PMC9249703.
4)

Lillie P, Thaker H, Moss P, et al. Healthcare-associated discitis in the era of antimicrobial resistance. J Clin Rheumatol 2008;14:234-7.

Magnetic resonance image-guided laser interstitial thermal therapy for glioblastoma

Magnetic resonance image-guided laser interstitial thermal therapy for glioblastoma


see Glioblastoma treatment.

see Magnetic resonance image-guided laser interstitial thermal therapy for intracranial tumor.


Magnetic Resonance Image-Guided Laser Interstitial Thermal Therapy (MRg-LITT) is an innovative and minimally invasive medical procedure used in the treatment of certain brain tumors, including glioblastoma.

Here’s an overview of how MRg-LITT works for glioblastoma:

Patient Selection: MRg-LITT is typically considered for patients who have glioblastoma that is difficult to access with traditional surgical methods or for patients who are not candidates for open surgery due to various reasons, such as the tumor’s location within critical brain regions.

Imaging and Planning: Before the procedure, high-resolution magnetic resonance imaging (MRI) scans are used to precisely locate and map the tumor. These images are used to plan the laser treatment.

Laser Ablation: During the MRg-LITT procedure, the patient is typically awake under local anesthesia. A small incision is made in the skull, and a thin, flexible laser probe is inserted into the brain. The laser probe has an optical fiber that delivers laser energy directly to the tumor.

Real-Time MRI Guidance: The critical aspect of MRg-LITT is real-time MRI guidance. As the laser is activated, MRI scans are continuously performed to monitor the temperature changes and precisely control the heat distribution within the tumor and surrounding healthy tissue. This real-time feedback ensures that the tumor is effectively heated and destroyed while minimizing damage to healthy brain tissue.

Treatment Monitoring: The MRI images provide immediate feedback to the medical team, allowing them to adjust the laser’s power and position as needed to optimize tumor ablation.

Thermal Ablation: The laser heats and destroys the tumor cells through thermal ablation, effectively killing the cancerous tissue. The procedure is carefully monitored to ensure the entire tumor is treated.

Post-Procedure Care: After the laser ablation, the probe is removed, and the incision is closed. Patients typically stay in the hospital for a short period for observation and recovery.

MRg-LITT offers several advantages for the treatment of glioblastoma:

Minimally Invasive: It involves a smaller incision compared to traditional open surgery, leading to reduced trauma and a shorter recovery time. Precise Targeting: Real-time MRI guidance allows for highly precise targeting and monitoring of the tumor, minimizing damage to healthy brain tissue. Outpatient Potential: In some cases, MRg-LITT can be performed on an outpatient basis or with shorter hospital stays. Reduced Risk: It may be suitable for patients with tumors in challenging or critical brain areas. However, it’s important to note that MRg-LITT is not suitable for all cases of glioblastoma. Patient eligibility and the choice of treatment method depend on various factors, including tumor size, location, and the patient’s overall health. Treatment decisions are typically made in consultation with a multidisciplinary team of medical professionals, including neurosurgeons, oncologists, and radiologists. Additionally, the long-term effectiveness of MRg-LITT for glioblastoma is an area of ongoing research and clinical trials.

50 GBM patients treated with LITT, with regard to safety, efficacy, and outcomes.

Kamath et al. performed a retrospective descriptive study of patients with histologically proven GBM who underwent LITT. Data collected included demographics, tumor location and volume, tumor genetic markers, treatment volume, perioperative complications, and long-term follow-up data.

They performed 58 LITT treatments for GBM in 54 patients over 5.5 yr. Forty-one were recurrent tumors while 17 were frontline treatments. Forty GBMs were lobar in location, while 18 were in deep structures (thalamus, insula, corpus callosum). Average tumor volume was 12.5 ± 13.4 cm3. The average percentage of tumors treated with the yellow thermal damage threshold (TDT) line (dose equivalent of 43°C for 2 min) was 93.3% ± 10.6%, and with the blue TDT line (dose equivalent of 43°C for 10 min) was 88.0% ± 14.2%. There were 7 perioperative complications (12%) and 2 mortalities (3.4%). Median overall survival after LITT for the total cohort was 11.5 mo, and median progression-free survival was 6.6 mo.

LITT appears to be a safe and effective treatment for GBM in properly selected patients 1).


A study included patients with de novo or recurrent glioblastoma of the corpus callosum (n = 15). The mean patient age was 54.7 yr. The mean pretreatment Karnofsky Performance Scale score was 80.7 and there was no significant difference between subgroups. The mean tumor volume was 18.7 cm3. Hemiparesis occurred in 26.6% of patients. Complications were more frequent in patients with tumors >15 cm3 (RR 6.1, P = .009) and were associated with a 32% decrease in survival postLITT. Median progression-free survival, survival postLITT, and overall survival were 3.4, 7.2, and 18.2 mo, respectively.

LITT is a safe and effective treatment for glioblastoma of the corpus callosum and provides survival benefits comparable to subtotal surgical resection with adjuvant chemoradiation. LITT-associated complications are related to tumor volume and can be nearly eliminated by limiting the procedure to tumors of 15 cm3 or less 2).


A 51-year-old male presented after a fall with progressive dizziness, ataxia, and worsening headaches with a small, frontal ring-enhancing lesion. After clinical and radiographic progression, the patient underwent a stereotactic biopsy, confirming an IDH-WT World Health Organization Grade IV Glioblastoma, followed by LITT. The patient was subsequently started on adjuvant temozolomide, and 60 Gy fractionated – radiotherapy to the post-LITT tumor volume. After 3 months, surgical debulking was conducted due to perilesional vasogenic edema and cognitive decline, with H&E staining demonstrating perivascular lymphocytic infiltration. Postoperative serial imaging over 3 years showed no evidence of tumor recurrence. The patient is currently alive 9 years after diagnosis. Multiplex immunofluorescence imaging of pre-LITT and post-LITT biopsies showed increased CD8 and activated macrophage infiltration and programmed death ligand 1 expression. This is the first depiction of the in-situ immune response to LITT and the first human clinical presentation of increased CD8 infiltration and programmed death ligand 1 expression in post-LITT tissue. The findings point to LITT as a treatment approach with the potential for long-term delay of recurrence and improving response to immunotherapy 3)

Magnetic Resonance Image-Guided Laser Interstitial Thermal Therapy (MRg-LITT)

What is MRg-LITT primarily used for? a. Treating lung cancer b. Treating glioblastoma c. Treating breast cancer d. Treating skin disorders

Why is MRg-LITT considered for glioblastoma patients? a. It is less expensive than traditional surgery. b. It involves a larger incision than traditional surgery. c. It is suitable for all cases of glioblastoma. d. It is considered when traditional surgery is challenging or not an option.

What is the first step in the MRg-LITT procedure? a. Administering chemotherapy b. Conducting a stereotactic biopsy c. Performing a CT scan d. Using high-resolution MRI scans for tumor mapping

During the MRg-LITT procedure, what delivers laser energy directly to the tumor? a. A scalpel b. A robotic arm c. An optical fiber in a laser probe d. A radiation beam

What is the critical aspect of MRg-LITT that ensures precise treatment and minimal damage to healthy tissue? a. Real-time MRI guidance b. Post-operative care c. Chemotherapy administration d. Surgical incision size

How is the laser energy used during MRg-LITT to treat the tumor? a. It cools down the tumor. b. It freezes the tumor. c. It heats and destroys the tumor cells through thermal ablation. d. It directly removes the tumor.

What is one of the advantages of MRg-LITT for glioblastoma treatment? a. Longer hospital stays b. Increased trauma compared to traditional surgery c. Outpatient potential d. Risk reduction for all patients

What factors determine patient eligibility and the choice of treatment method for MRg-LITT? a. The patient’s hair color b. The patient’s blood type c. Tumor size, location, and overall health d. The patient’s age and gender

What is the primary focus of the case series study mentioned? a. The history of MRg-LITT b. The benefits of chemotherapy c. The safety and outcomes of MRg-LITT in GBM patients d. The development of new surgical instruments

According to the study by Kamath et al., what percentage of patients experienced perioperative complications related to MRg-LITT? a. 0% b. 3.4% c. 12% d. 26.6%

Answers:

b. Treating glioblastoma d. It is considered when traditional surgery is challenging or not an option. d. Using high-resolution MRI scans for tumor mapping c. An optical fiber in a laser probe a. Real-time MRI guidance c. It heats and destroys the tumor cells through thermal ablation. c. Outpatient potential c. Tumor size, location, and overall health c. The safety and outcomes of MRg-LITT in GBM patients c. 12%


1)

Kamath AA, Friedman DD, Akbari SHA, Kim AH, Tao Y, Luo J, Leuthardt EC. Glioblastoma Treated With Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy: Safety, Efficacy, and Outcomes. Neurosurgery. 2019 Apr 1;84(4):836-843. doi: 10.1093/neuros/nyy375. PMID: 30137606; PMCID: PMC6425465.
2)

Beaumont TL, Mohammadi AM, Kim AH, Barnett GH, Leuthardt EC. Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy for Glioblastoma of the Corpus Callosum. Neurosurgery. 2018 Sep 1;83(3):556-565. doi: 10.1093/neuros/nyx518. PMID: 29438526; PMCID: PMC6939409.
3)

Chandar JS, Bhatia S, Ingle S, Mendez Valdez MJ, Maric D, Seetharam D, Desgraves JF, Govindarajan V, Daggubati L, Merenzon M, Morell A, Luther E, Saad AG, Komotar RJ, Ivan ME, Shah AH. Laser Interstitial Thermal Therapy Induces Robust Local Immune Response for Newly Diagnosed Glioblastoma with Long-term Survival and Disease Control. J Immunother. 2023 Sep 19. doi: 10.1097/CJI.0000000000000485. Epub ahead of print. PMID: 37727953.

Propofol

Propofol

Propofol is a potent intravenous (IV) anesthetic agent used for the induction and maintenance of general anesthesia during surgical procedures and medical interventions. It is one of the most widely used and recognized anesthesia drugs in clinical practice. Here are some key points about propofol:

Induction of Anesthesia: Propofol is often used to rapidly induce anesthesia in patients before surgery or medical procedures. It causes rapid loss of consciousness and a state of general anesthesia.

Maintenance of Anesthesia: In addition to induction, propofol can also be used to maintain anesthesia during surgery. Anesthesia providers can adjust the infusion rate to maintain the desired level of anesthesia.

Rapid Onset and Offset: One of the advantages of propofol is its rapid onset of action, typically within seconds after IV administration. It also has a relatively short duration of action, which allows for a quicker recovery when compared to some other anesthetic agents.

Sedation and Amnesia: Propofol induces a state of sedation, amnesia, and unconsciousness. Patients under the influence of propofol do not feel pain or remember the surgical procedure.

Controlled Infusion: Propofol is administered as a controlled infusion through an IV line. The infusion rate is adjusted to maintain the desired level of anesthesia throughout the procedure.

Side Effects: Common side effects of propofol include respiratory depression, hypotension (low blood pressure), and pain at the injection site. These effects are closely monitored during surgery.

Antiemetic Properties: Propofol has antiemetic (anti-nausea and anti-vomiting) properties, making it useful in preventing postoperative nausea and vomiting.

Propofol-Related Infusion Syndrome (PRIS): In rare cases, prolonged and high-dose use of propofol can lead to a condition called PRIS, which may result in metabolic acidosis, heart and kidney dysfunction, and other serious complications. This is why propofol use is carefully monitored, and its dosage is controlled.

Not an Analgesic: It’s important to note that propofol is not an analgesic (pain reliever). It is typically used in conjunction with analgesic medications such as opioids to manage pain during and after surgery.

Intravenous Administration Only: Propofol is administered exclusively through IV injection. It is not available in oral or other forms.

Rapid Recovery: Due to its short duration of action, patients typically wake up quickly and experience a clear-headed recovery after discontinuation of propofol.

Color and Lipid Emulsion: Propofol is known for its milky white appearance, and it is formulated as a lipid emulsion. This unique formulation contributes to its rapid onset and offset of action.

Special Considerations: Dosage and administration of propofol are tailored to the patient’s age, weight, medical condition, and the type of surgery being performed.

see Agents generally used for induction.



Reduces cerebral metabolismCBF and ICP. Has been described for cerebral protection and for sedation. Short half-life permits rapid awakening which may be useful for awake craniotomy. Not analgesic.

The exact mechanism of action unknown. Short half-life with no active metabolites. May be used for induction and as a continuous infusion during total intravenous anesthesia (TIVA). It causes a dose-dependent decrease in mean arterial blood pressure (MAP) and ICP.

It is more rapidly cleared than and has largely replaced thiopental.


Dexmedetomidine (Precedex®). Alpha 2 adrenergic receptor agonist, used for control of hypertension postoperatively, as well as for its sedating qualities during awake craniotomy either alone or in conjunction with propofol.


Propofol has a mild effect on evoked potential (EP): total anesthesia with propofol causes less EP depression than inhalational agents at the same depth of anesthesia 1).


Propofol (INN, marketed as Diprivan by Fresenius Kabi) is a short-acting, intravenously administered hypnotic/amnestic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine. It is approved for use in more than 50 countries, and generic versions are available.

Chemically, propofol is not related to barbiturates and has largely replaced sodium thiopental (Pentothal) for induction of anesthesia because recovery from propofol is more rapid and “clear” when compared with thiopental. Propofol is not considered an analgesic, so opioids such as fentanyl may be combined with propofol to alleviate pain.

Propofol has been referred to as milk of amnesia (a play on words of milk of magnesia), because of the milk-like appearance of its intravenous preparation.

It is on the World Health Organization’s List of Essential Medicines, the most important medications needed in a health system.


Level II: propofol may control ICP after several hours of dosing, but it does not improve mortality or 6-month outcomes. ✖ Caution: high-dose propofol (total dose > 100 mg/kg for > 48 hrs) can cause significant morbidity (see propofol infusion syndrome).

℞: 0.5 mg/kg test dose, then 20–75 mcg/kg/min infusion. Increase by 5–10 mcg/kg/min q 5–10 minutes PRN ICP control (do not exceed 83 mcg/kg/min = 5 mg/kg/hr).

Side effects include propofol infusion syndrome. Use with caution at doses > 5 mg/kg/hr or at any dose for > 48 hrs.


Propofol, an established hypnotic anesthetic agent, has been shown to ameliorate neuronal injury when given after injury in a number of experimental brain studies. We tested the hypothesis that propofol pretreatment confers neuroprotection against SBI and will reduce cerebral edema formation and neurobehavioral deficits in our rat population. Sprague-Dawley rats were treated with low- and high-dose propofol 30 min before SBI. At 24 h post-injury, brain water content and neurobehavioral assessment was conducted based on previously established models. In vehicle-treated rats, SBI resulted in significant cerebral edema and higher neurological deficit scores compared with sham-operated rats. Low- or high-dose propofol therapy neither reduced cerebral edema nor improved neurologic function. The results suggest that propofol pretreatment fails to provide neuroprotection in SBI rats. However, it is possible that an SBI model with less magnitude of injury or that propofol re-dosing, given the short-acting pharmacokinetic property of propofol, may be needed to provide definitive conclusions 2).


Propofol concentration needed for induction of unconsciousness in 50% of patients is reduced in Parkinson’s Disease patients 3).

Malekmohammadi et al. from the Department of Neurosurgery, University of California, Los Angeles, collected local field potentials (LFPs) in 12 awake and anesthetized PD patients undergoing DBS implantation. Spectral power of β (13-35 Hz) and high-frequency oscillations (HFOs: 200-300 Hz) was compared across the pallidum.

Propofol suppressed GPi power by > 20 Hz while increasing power at lower frequencies. A similar power shift was observed in GPe; however, power in the high β range (20-35 Hz) increased with propofol. Before anesthesia both β and HFO activity were significantly greater at the GPi (χ2 = 20.63 and χ2 = 48.81, p < 0.0001). However, during anesthesia, we found no significant difference across the pallidum (χ2 = 0.47, p = 0.79, and χ2 = 4.11, p = 0.12).

GPi and GPe are distinguishable using LFP spectral profiles in the awake condition. Propofol obliterates this spectral differentiation. Therefore, LFP spectra cannot be relied upon in the propofol-anesthetized state for functional mapping during DBS implantation 4).


We analyzed 231 neurosurgery patients. In all patients, propofol was used for standard anesthesia induction. Patient demographics, medical histories, fasting duration, percentage weight loss, baseline blood pressure, and PPV during normal tidal volume breathing and that during forced inspiratory breathing (PPVfi) were recorded. Hemodynamic changes within 10 minutes of intubation were observed. Patients developing hypotension and severe hypotension were determined; lowest mean arterial pressure (MAP) and systolic arterial pressure (SAP) values were recorded, and their differences relative to baseline values were calculated. RESULTS: The incidence of hypotension was 18.6%. Both percentage weight loss and PPVfi were correlated with the changes in MAP and SAP. A PPVfi>14 identified all observed hypotensive episodes with 86% sensitivity and 86.2% specificity, whereas percentage weight loss >1.75% identified all observed hypotensive episodes with 81.4% sensitivity and 70.7% specificity. Furthermore, PPVfi>16.5 identified severe hypotension with 85% sensitivity and 90.5% specificity, whereas percentage weight loss >1.95% identified severe hypotension with 85% sensitivity and 73% specificity. CONCLUSIONS: Percentage weight loss and PPVfi are good predictors of hypotension after anesthesia induction and, thus, may allow anesthesiologists to adopt preventative measures and ensure safer anesthesia induction 5).

Acute psychosis following propofol in a patient with Parkinson’s disease: effects of a GABAdopamine imbalance 6).

What is the primary use of Propofol in clinical practice? a) Pain relief b) Induction and maintenance of general anesthesia c) Treatment of hypertension d) Treatment of epilepsy

What is the advantage of using Propofol for induction of anesthesia? a) It provides prolonged anesthesia. b) It has a slow onset of action. c) It causes rapid loss of consciousness. d) It is available in oral form.

How does Propofol compare to some other anesthetic agents in terms of its duration of action? a) It has a longer duration of action. b) It has a shorter duration of action. c) It has no duration of action. d) Its duration of action depends on the patient’s age.

What state does Propofol induce in patients during surgery? a) Euphoria b) Sedation and amnesia c) Hyperactivity d) Increased pain perception

How is Propofol administered during surgery? a) Orally b) Intramuscularly c) Subcutaneously d) As a controlled IV infusion

What is one of the common side effects of Propofol during surgery? a) Increased heart rate b) Hypertension (high blood pressure) c) Respiratory depression d) Elevated body temperature

What property of Propofol makes it useful in preventing postoperative nausea and vomiting? a) Analgesic effect b) Antidepressant effect c) Antiemetic properties d) Anticoagulant effect

What rare condition can occur with prolonged and high-dose use of Propofol? a) Hypothermia b) Propofol overdose c) Propofol-related infusion syndrome (PRIS) d) Propofol addiction

Which of the following statements about Propofol is true? a) It is commonly used as a standalone analgesic. b) It is available in various forms, including oral tablets. c) It is administered exclusively through IV injection. d) It is primarily used as an anticoagulant.

Why is Propofol known as the “milk of amnesia”? a) It has a white color. b) It is derived from milk. c) It tastes like milk. d) It causes amnesia-like effects.

Answers:

b) Induction and maintenance of general anesthesia c) It causes rapid loss of consciousness. b) It has a shorter duration of action. b) Sedation and amnesia d) As a controlled IV infusion c) Respiratory depression c) Antiemetic properties c) Propofol-related infusion syndrome (PRIS) c) It is administered exclusively through IV injection. a) It has a white color.


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Vinckier F, Gaillard R, Taylor G, Murray GK, Plaze M, Bourdillon P, Perin-Dureau F. Acute psychosis following propofol in a patient with Parkinson’s disease: effects of a GABA-dopamine imbalance. Psychiatry Clin Neurosci. 2022 Mar 29. doi: 10.1111/pcn.13360. Epub ahead of print. PMID: 35352434.