Lumbar puncture is a useful diagnostic and treatment tool. Although serious events are seldom, they can be detrimental. A precaution not to underestimate such events in practicing lumbar, especially in patients with suboptimum coagulation state. Image-guided procedure can be useful and should be considered in appropriately selected patients 1).
In a Danish cohort study, risk of spinal hematoma following lumbar puncture was 0.20% among patients without coagulopathy and 0.23% among those with coagulopathy. Although these findings may inform decision-making about lumbar puncture by describing rates in this sample, the observed rates may reflect bias due to physicians selecting relatively low-risk patients for lumbar puncture 2).
It is estimated that approximately 4% of symptomatic spinal hematomas are related to traumatic LP. They are commonly located inclusively with the epidural space in 75% of the cases, whereas subarachnoid hemorrhage and spinal subdural hematoma can be found in 15.7% and 4.1%, respectively. Multi-compartmental spinal hematomas are rare and thought to present in 0.33% 3).
In clinical practice, few carry out postprocedural investigation for spinal hematoma unless the patient reports sensory or motor changes after the procedure. In a meta-analysis, approximately 85% of symptomatic spinal hematomas required surgical intervention 4)
Surgery is indicated for symptomatic patients with reported complete neurological recovery in almost 40%. The timing of surgery is vital and associated with improved neurological outcome when done in less than 36 hours 5).
Nevertheless, symptomatic spinal hematoma is a critical condition and we emphasize that surgical intervention should be considered at a low threshold for urgent decompression to optimize overall clinical outcome. Coagulopathy is an important risk factor that should not be underestimated in planning for LP. The presence of pre-existing coagulopathy was found to be a significant poor prognostic factor regardless of surgical intervention. Therefore, an early investigation with spinal MRI should be obtained to rule out an evolving spinal hematoma. Mortality was reported high in patients with compressive cervical spinal epidural hematomas and cardiovascular disease 6).
A case for a patient with Burkitt lymphoma who presented with mild neuroaxial symptoms. An urgent cerebrospinal fluid sample was required which was taken after correcting his platelets count to 53.4 × 109/L. He developed a massive multi-compartmental thoracolumbar hematoma with acute cauda equine syndrome requiring surgical intervention. Despite aggressive management, he remained permanently paraplegic with functional status that negatively affected his overall outcome 7).
Bodilsen J, Mariager T, Vestergaard HH, Christiansen MH, Kunwald M, Lüttichau HR, Kristensen BT, Bjarkam CR, Nielsen H. Association of Lumbar Puncture With Spinal Hematoma in Patients With and Without Coagulopathy. JAMA. 2020 Oct 13;324(14):1419-1428. doi: 10.1001/jama.2020.14895. PMID: 33048155.
Groen RJ, van Alphen HA. Operative treatment of spontaneous spinal epidural hematomas: a study of the factors determining postoperative outcome. Neurosurgery. 1996 Sep;39(3):494-508; discussion 508-9. doi: 10.1097/00006123-199609000-00012. PMID: 8875479.
Mendes et al. presented the case of a 49-year-old woman diagnosed with idiopathic trigeminal neuralgia refractory to pharmacological treatment. After failure of puncture by conventional fluoroscopy for percutaneous gasserian ganglion balloon compression due to a narrow foramen ovale, the patient was submitted to puncture guided by computed tomography.
Alternative imaging methods, such as computed tomography, should be considered when Percutaneous Foramen Ovale Puncture by conventional single-plane fluoroscopy fails, to minimize the risk of potential complications triggered by frustrated puncture attempts 1).
Cannulation procedures, including those utilizing neuronavigational technology, are occasionally complicated by anatomical variation of the FO, sometimes resulting in miscannulation and subsequent adverse events. The FO, while commonly thought of as oval-shaped, has also been described as “almond,” “banana,” “D shape,” “pear,” and “triangular.” 2).
Guo et al., described a technique that includes a stereotactic approach in the preoperative plan in cases where the foramen ovale is difficult to access for radiofrequency thermocoagulation of the Gasserian ganglion.
The study included 395 patients for whom three-dimensional computed tomographic reconstruction of the skull base, maxilla, and mandible was conducted before surgery. Accessibility of the foramen ovale was defined using numerical data from the three-dimensional computed tomographic reconstruction images. In those patients for whom accessibility of the foramen ovale was considered difficult, the authors used a stereotactic frame to design an individual operative plan. Adjustments of a single point of data,-that is, a change in X axis, Y axis, or an arc angle-were guided by radiographic fluoroscopy images. After verifying successful cannulation and electroneurophysiology, thermocoagulation targets-especially multiple targets recorded as data on the Z axis of the stereotactic approach-were identified and treated.
There were 24 patients who met the predetermined criteria for having a difficult-to-access foramen ovales-that is, they had at least two contributing factors and/or involvement of division V1 . Twenty-one of the 24 patients required a single satisfactory puncture; three patients required two to three punctures to successfully access the foramen ovale. There were no permanent complications from the procedure.
The authors conclude that this stereotactic approach combined with three-dimensional computed tomographic reconstruction model can improve the accuracy, safety, and efficiency of percutaneous radiofrequency thermocoagulation in patients with trigeminal neuralgia for whom the foramen ovale is difficult to access 4).
Ding et al., assessed the feasibility of accessing the Gasserian ganglion through the FO from a mandibular angle under computed tomography (CT) and neuronavigation guidance.A total of 108 patients with TN were randomly divided into 2 groups (Group G and Group H) using a random number table. In Group H, anterior Hartel approach was used to puncture the FO; whereas in Group G, a percutaneous puncture through a mandibular angle was used to reach the FO. In both groups, procedures were guided by CT imaging and neuronavigation. The success rates, therapeutic effects, complications, and recurrence rates of the 2 groups were compared.The puncture success rates in Group H and Group G were 52/54 (96.30%) and 49/54 (90.74%), respectively (P = 0.24). The 2 procedural failures in Group H were rescued by using submandibular trajectory, and the 5 failures in Group G were successfully reapproached by Hartel method. Therapeutic effects as measured by Barrow Neurological Institute Pain Scale (P = 0.03) and quality of life (QOL) scores (P = 0.04) were significantly better in Group G than those in Group H at 36 months posttreatment. Hematoma developed in 1/54 (1.85%) cases in Group H, and no cases of hematoma were observed in Group G (P = 0.33). In Group H, RFT resulted in injury to the unintended trigeminal nerve branches and motor fibers in 27/52 (51.92%) cases; in Group G, it resulted in the same type of injury in 7/49 cases (14.29%) (P < 0.01). In Group H, the 24- and 36-month recurrence rates were 12/51 (23.53%) and 20/51 (39.22%), respectively; in Group G, these recurrence rates were 7/49 (12.24%) and 9/49 (16.33%, P = 0.03), respectively.CT- and neuronavigation-guided puncture from a mandibular angle through the FO into the Gasserian ganglion can be safely and effectively used to deliver RFT for the treatment of pTN. This method may represent a viable option to treat TN in addition to Hartel approach 5).
The goals of a study of Peris-Celda et al., were to demonstrate the anatomical basis of complications related to FO puncture, and provide anatomical landmarks for improvement of safety, selective lesioning of the trigeminal nerve (TN), and optimal placement of electrodes.
Both sides of 50 dry skulls were studied to obtain the distances from the FO to relevant cranial base references. A total of 36 sides from 18 formalin-fixed specimens were dissected for Meckel cave and TN measurements. The best radiographic projection for FO visualization was assessed in 40 skulls, and the optimal trajectory angles, insertion depths, and topographies of the lesions were evaluated in 17 specimens. In addition, the differences in postoperative pain relief after the radiofrequency procedure among different branches of the TN were statistically assessed in 49 patients to determine if there was any TN branch less efficiently targeted.
Most severe complications during FO puncture are related to incorrect needle placement intracranially or extracranially. The needle should be inserted 25 mm lateral to the oral commissure, forming an approximately 45° angle with the hard palate in the lateral radiographic view, directed 20° medially in the anteroposterior view. Once the needle reaches the FO, it can be advanced by 20 mm, on average, up to the petrous ridge. If the needle/radiofrequency electrode tip remains more than 18 mm away from the midline, injury to the cavernous carotid artery is minimized. Anatomically there is less potential for complications when the needle/radiofrequency electrode is advanced no more than 2 mm away from the clival line in the lateral view, when the needle pierces the medial part of the FO toward the medial part of the trigeminal impression in the petrous ridge, and no more than 4 mm in the lateral part. The 40°/45° inferior transfacial-20° oblique radiographic projection visualized 96.2% of the FOs in dry skulls, and the remainder were not visualized in any other projection of the radiograph. Patients with V1 involvement experienced postoperative pain more frequently than did patients with V2 or V3 involvement. Anatomical targeting of V1 in specimens was more efficiently achieved by inserting the needle in the medial third of the FO; for V2 targeting, in the middle of the FO; and for V3 targeting, in the lateral third of the FO.
Knowledge of the extracranial and intracranial anatomical relationships of the FO is essential to understanding and avoiding complications during FO puncture. These data suggest that better radiographic visualization of the FO can improve lesioning accuracy depending on the part of the FO to be punctured. The angles and safety distances obtained may help the neurosurgeon minimize complications during FO puncture and TN lesioning 6).
Koizuka et al., presented a new method for percutaneous radio-frequency thermocoagulation of the Gasserian ganglion, in which computed tomography (CT) fluoroscopy is used to guide needle placement.
In the present study, 15 patients with trigeminal neuralgia underwent percutaneous radio-frequency thermocoagulation of the Gasserian ganglion guided by high-speed real-time CT fluoroscopy.
RESULTS: Trigeminal neuralgia was improved in all patients after treatment without any severe complications. Moderate dysesthesia occurred in only one case.
CT fluoroscopy-guided percutaneous radio-frequency thermocoagulation of the Gasserian ganglion was safe, quick, and effective for patients with intractable idiopathic trigeminal neuralgia 7).
Mendes PD, Martins da Cunha PH, Monteiro KKO, Quites LV, Fonseca Filho GA. Percutaneous Foramen Ovale Puncture: Usefulness of Intraoperative CT Control, in the Eventuality of a Narrow Foramen [published online ahead of print, 2020 Sep 16]. Stereotact Funct Neurosurg. 2020;1-4. doi:10.1159/000509821
Zdilla MJ, Fijalkowski KM. The Shape of the Foramen Ovale: A Visualization Aid for Cannulation Procedures. J Craniofac Surg. 2016 Dec 23. doi: 10.1097/SCS.0000000000003325. [Epub ahead of print] PubMed PMID: 28027173.
Guo Z, Wu B, Du C, Cheng M, Tian Y. Stereotactic Approach Combined with 3D CT Reconstruction for Difficult-to-Access Foramen Ovale on Radiofrequency Thermocoagulation of the Gasserian Ganglion for Trigeminal Neuralgia. Pain Med. 2016 Sep;17(9):1704-16. doi: 10.1093/pm/pnv108. Epub 2016 Feb 13. PubMed PMID: 26874883.
Ding W, Chen S, Wang R, Cai J, Cheng Y, Yu L, Li Q, Deng F, Zhu S, Yu W. Percutaneous radiofrequency thermocoagulation for trigeminal neuralgia using neuronavigation-guided puncture from a mandibular angle. Medicine (Baltimore). 2016 Oct;95(40):e4940. PubMed PMID: 27749549; PubMed Central PMCID: PMC5059051.
Reported in the journal Nature Communications, the Vall d’Hebron Institute of Oncology´s (VHIO) Gene Expression and Cancer Group, led by Joan Seoane, has pioneered research evidencing the use of cerebrospinal fluid (CSF) as liquid biopsy for the potential prognosis, treatment, identification and tracking of brain tumor genomic alterations not only in real time but over time. Concentrations of circulating central nervous system tumor DNA are very low in plasma, but very high in CSF.
A liquid biopsy in CSF, obtained by lumbar puncture, is much less invasive and less risky for the patient than traditional procedures used to extract brain tissue samples. This study was partly financed by a grant from the Spanish Association against Cancer (AECC) awarded to Joan Seoane – support which has not only fuelled the research efforts that have now led to the proof of concept of this approach as well as promising new direction in the study of brain cancer and metastases. Findings also show that this circulating tumor DNA can both facilitate and complement the diagnosis of leptomeningeal carcinomatosis (LC).
The identification of each and every tumor type along with each respective, individual molecular makeup is critical in tackling cancer with greater precision. To date, extraction of brain tumor tissue for analysis has consisted of a punch biopsy or surgery. Such approaches suppose risk per se and do not necessarily facilitate access to a representative part of the tumor. A new technique, liquid biopsy, has been recently and successfully developed at research level, which detects a tumor’s specific mutations by means of a plasma sample containing circulating tumor DNA.
As reflected in recent literature, the liquid biopsy ´policing´ of cancer is not only promising a more precise treatment selection for each individual patient, but could also help us to be steps ahead of cancer´s next move. Compared to traditional tissue biopsy, it is a much less invasive technique, and represents a significant forward step towards better detecting cancer mutations, tracking the evolution of disease, as well as predicting response to therapy. “With these important considerations in mind we looked for a way to apply this type of liquid biopsy to brain cancer, especially in view of the obstacles associated with accessing this tumor type”, explains Joan Seoane, Director of Translational Research at VHIO, ICREA Professor, and Professor at the Universitat Autònoma de Barcelona (UAB), who led the study.
Liquid biopsy in plasma has already proven useful in metastatic colon, breast and lung cancer, but not as successful for brain tumors, for several reasons. “Our main limitation was that circulating tumor DNA levels for brain tumors are very low in plasma. But the brain has its own closed circuit of fluid, cerebrospinal fluid, which bathes the brain and spinal cord, and is therefore in direct contact with tumor cells,” continues Seoane, “and we found circulating tumor DNA in CSF at such high levels that we were able to detect and characterize tumors with a high degree of sensitivity”.
Glioblastoma is the most common and aggressive malignant brain tumor. One of the characteristics of glioblastoma is that the tumor always reappears after time. Added to the mix of difficulties associated with this tumor type, there are currently few therapeutic options available and accessing the tumor is problematic. Upon diagnosis, the tumor is surgically resected as a first step in treatment, after which time the patient receives both radiotherapy and chemotherapy. However, the tumor nearly always recurs and, when it does, it presents different genetic alterations from the primary tumor. This scenario severely hampers therapeutic possibilities since the new tumor will differ from the previous one, thus requiring different therapy. Performing traditional tissue biopsy on a relapsed tumor is seldom indicated. “Mirroring certain successes to-date of applying liquid biopsy across other tumor types, the use of tumor DNA circulating in CSF as a liquid biopsy for brain tumors could be much less invasive than standard tissue biopsy to characterize the genetic alterations of the new tumor. This new approach to liquid biopsy in CSF could help, in some cases, to consider novel, more specific and targeted experimental therapies, which could in turn also improve clinical response”, explains Josep Tabernero, Director of VHIO, Head of the Medical Oncology Department of Vall d’Hebron University Hospital, co-author of the study and a leading reference in the novel field of liquid biopsy.
The study also focused on leptomeningeal carcinomatosis—the tumor infiltration of the fine film that covers the brain and spinal cord and which occurs as a metastasis of other tumors. Its diagnosis is complicated on imaging tests and the possibility of “catching” a tumor cell for study by lumbar puncture is remote. “Compared to plasma, cerebrospinal fluid better captures the mutations in patients with brain tumors. The possibility of studying DNA fragments in this fluid by liquid biopsy, as we have done, greatly expands diagnostic possibilities, improves stratification based on genetic profiling, facilitates better and less invasive monitoring of patients. Our findings should also ultimately translate in clinical benefit for certain patients with brain tumors”, says Leticia De Mattos-Arruda, first author of the paper and member of Joan´s Group. Primary brain tumors and metastases, genetically different tumors
Metastasis is the most common cause of death from cancer and brain tumors formed through this process are ten times more common than primary tumors. Patients with brain metastasis tend to present a poor prognosis and do not usually respond to treatment. 200,000 cases are diagnosed every year in the United States alone and mean survival is 3 to 27 months after metastasis. Recent studies have shown that, due to the tumor environment, brain metastases evolve independently, developing shared genetic alterations that, in half of the cases, evade detection in the primary tumor. This explains why the treatment used for the primary tumor does not usually work against metastases. “This new advance represents a potential game changer in brain cancer, whether they are primary tumors, relapses or metastases. As recently observed in a study in which we participated*, 53% of metastatic brain tumors present different genetic alterations from those found in the first biopsies of primary tumors,” affirms Joan. Towards precision oncology against brain tumors
Joan Seoane and his team have taken an important next step towards rendering anti-cancer therapy more precise in brain cancer: “the identification of these alterations by CSF-circulating tumor DNA will enable us to identify the characteristics of metastasis and facilitate the development of personalized treatments.” Furthermore, liquid biopsy for brain tumors opens a new, pioneering line of research into biomarkers that enable us to monitor the progress of the disease and ultimately help us to be steps ahead of cancer´s next move. “This study of circulating tumor DNA has enabled us to monitor tumors by liquid biopsy of CSF. This approach is therefore a potential tool for stratifying patients, assessing their prognoses, and closely monitoring the course of disease and their response to therapy in a minimally invasive manner,” adds Josep Tabernero. Tumor monitoring will enable us to evaluate the effect of treatment and to assess drug effectiveness as the cancer progresses.
Considering the potential of liquid biopsies that we are now witnessing at research level, there is every indication that this technique developed at VHIO, will be fundamental in the future diagnosis and treatment of brain tumors.