Histopathological correlation of brain tumor recurrence vs. radiation effect post-radiosurgery as detected by MRI contrast clearance analysis: a validation study.

PURPOSE: The differentiation between adverse radiation effects (ARE) and tumor recurrence or progression (TRP) is a major decision-making point in the follow-up of patients with brain tumors. The advent of immunotherapy, targeted therapy and radiosurgery has made this distinction difficult to achieve in several clinical situations. Contrast clearance analysis (CCA) is a useful technique that can inform clinical decisions but has so far only been histologically validated in the context of high-grade gliomas. METHODS: This is a series of 7 patients, treated between 2018 and 2023, for various brain pathologies including brain metastasis, atypical meningioma, and high-grade glioma. MRI with contrast clearance analysis was used to inform clinical decisions and patients underwent surgical resection as indicated. The histopathology findings were compared with the CCA findings in all cases. RESULTS: All seven patients had been treated with gamma knife radiosurgery and were followed up with periodic MR imaging. All patients underwent CCA when the necessity to distinguish tumor recurrence from radiation necrosis arose, and subsequently underwent surgery as indicated. Concordance of CCA findings with histological findings was found in all cases (100%). CONCLUSIONS: Based on prior studies on GBM and the surgical findings in our series, delayed contrast extravasation MRI findings correlate well with histopathology across a wide spectrum of brain tumor pathologies. CCA can provide a quick diagnosis and have a direct impact on patients' treatment and outcomes.

Patient variables and referral paradigms associated with osteoporosis screening and treatment in neurosurgical patients undergoing kyphoplasty.

OBJECT Vertebral fractures are the most common osteoporotic fracture. Bone density testing and medical treatment with bisphosphonates or parathormone are recommended for all patients with an osteoporotic fracture diagnosis. Inadequate testing and treatment of patients presenting with low-impact fractures have been reported in various specialties. Similar data are not available from academic neurosurgery groups. The authors assessed compliance with treatment and testing of osteoporosis in patients with vertebral compression fractures evaluated by the authors' academic neurosurgery service, and patient variable and health-systems factors associated with improved compliance. METHODS Data for patients who underwent percutaneous kyphoplasty for compression fractures was retrospectively collected. Diagnostic and medical interventions were tabulated. Pre-, intra-, and posthospital factors that had been theorized to affect the compliance of patients with osteoporosis-related therapies were tabulated and statistically analyzed. RESULTS Less than 50% of patients with kyphoplasty received such therapies. Age was not found to correlate with other variables. Referral from a specialist rather than a primary care physician was associated with a higher rate of bone density screening, as well as vitamin D and calcium therapy, but not bisphosphonate/parathormone therapy. Patients who underwent preoperative evaluation by their primary care physician were significantly more likely to receive bisphosphonates compared with those only evaluated by a hospitalist. Patients with unprovoked fractures were more likely to undergo multiple surgeries compared with those with minor trauma. CONCLUSIONS These results suggest poor compliance with current standard of care for medical therapies in patients with osteoporotic compression fractures undergoing kyphoplasty under the care of an academic neurosurgery service.

Peroneal intraneural ganglion cysts at the fibular neck: the layered "U" surgical approach to the articular branch and superior tibiofibular joint.

BACKGROUND: Intraneural ganglia most commonly occur within the peroneal nerve near the fibular neck. Disconnection of the articular branch is required in their treatment. Surgical intervention can be challenging because of unfamiliarity with the region or scarring from previous surgery. METHOD: We present the layered "U" technique for peroneal intraneural ganglia with clinical examples. Dissection is carried down in parallel to the U-shaped course of the articular branch to provide optimal visualization and avoid injury to major branches of the nerve. CONCLUSION: This pathoanatomic approach provides direct and safe exposure of the articular branch of the common peroneal nerve.

Recurrent intraneural ganglion cysts: Pathoanatomic patterns and treatment implications.

The etiology of intraneural ganglion cysts has been poorly understood. This has resulted in the development of multiple surgical treatment strategies and a high recurrence rate. We sought to analyze these recurrences in order to provide a pathoanatomic explanation and staging classification for intraneural cyst recurrence. An expanded literature search was performed to identify frequencies and patterns in cases of intraneural ganglion cyst recurrences following primary surgery. Two univariate analyses were completed to identify associations between the type of revision surgery and repeat cyst recurrences. The expanded literature search found an 11% recurrence rate following primary surgery, including 64 recurrences following isolated cyst decompression (Group 1); six after articular branch resection (Group 2); and none following surgical procedures that addressed the joint (Group 3). Eight cases did not specify the type of primary surgery. In group 1, forty-eight of the recurrences (75%) were in the parent nerve, three involved only the articular branch, and one travelled along the articular branch in a different distal direction without involving the main parent nerve. In group 2, only one case (17%) recurred/persisted within the parent nerve, one recurred within a persistent articular branch, and one formed within a persistent articular branch and travelled in a different distal direction. Intraneural recurrences most commonly occur following surgical procedures that only target the main parent nerve. We provide proven or theoretical explanations for all identified cases of intraneural recurrences for an occult or persistent articular branch pathway.

Spinal accessory neuropathy following dual tunneling of lead extensions for motor cortex stimulation.

BACKGROUND: Spinal accessory nerve (SAN) injury is a known complication of surgery involving the posterior cervical triangle. Because the nerve lies in a plane that is traversed by extension leads for neuromodulation, the SAN is at risk during tunneling for these procedures. METHODS: We report a 50-year-old man who developed spinal accessory neuropathy after tunneling of two sets of extension leads through his neck to connect to the pulse generator at the chest wall. Immediately postoperatively, he developed severe right shoulder pain and trapezius weakness manifested as decreased shoulder abduction and scapular winging. RESULTS: Electromyography 2 months later confirmed a SAN injury. Ultrasonography demonstrated the SAN to be angulated between the two sets of extension leads in the posterior cervical triangle. Operative exploration confirmed this finding. Neurolysis was performed and the deep extension lead was relocated superficial to the nerve. Postoperatively, the patient had immediate resolution of his shoulder pain and an improved range of motion. CONCLUSION: As the indications for neuromodulation continue to grow, tunneling may be performed more frequently. It is our belief that the second pass through the neck of a dual extension lead system may inadvertently be directed deeply and poses an increased risk to the SAN.

Functional prediction of response to therapy prior to therapeutic intervention is associated with improved survival in patients with high-grade glioma.

Patients with high-grade glioma (HGG) have an extremely poor prognosis compounded by a lack of advancement in clinical care over the past few decades. Regardless of classification, most newly diagnosed patients receive the same treatment, radiation and temozolomide (RT/TMZ). We developed a functional precision oncology test that prospectively identifies individual patient's response to this treatment regimen. Tumor tissues isolated from patients with newly diagnosed HGG enrolled in 3D PREDICT REGISTRY were evaluated for response to chemotherapeutic agents using the 3D Predict™ Glioma test. Patients receiving RT/TMZ were followed for 2 years. Clinical outcomes including imaging, assessments, and biomarker measurements were compared to patient matched test-predicted therapy response. Median survival between test-predicted temozolomide responders and test-predicted temozolomide non-responders revealed a statistically significant increase in progression-free survival when using the test to predict response across multiple subgroups including HGG (5.8 months), glioblastoma (4.7 months), and MGMT unmethylated glioblastoma (4.7 months). Overall survival was also positively separated across the subgroups at 7.6, 5.1, and 6.3 months respectively. The strong correlation of 3D Predict Glioma test results with clinical outcomes demonstrates that this functional test is prognostic in patients treated with RT/TMZ and supports aligning clinical treatment to test-predicted response across varying HGG subgroups.

Expected motor function change following decompressive surgery for spinal metastatic disease.

Background: Motor function in patients with spinal metastatic disease (SMD) directly impacts a patient's ability to receive systemic therapy and overall survival. Spine surgeons may be in the challenging position to advise a patient on expected motor function outcomes and determine a patient's suitability as a surgical candidate. We present this study to provide this critical information on anticipated motor function change to spine surgeons. Methods: Consecutive patients undergoing spinal surgery for SMD at a National Cancer Institute-designated cancer institute were prospectively enrolled. Patient motor function status before and after surgery was assessed using the standard 0 to 5 five-point muscle strength grading scale. The difference in presurgical and postsurgical motor function (proximal and distal) was used to assess motor function changes following surgery. Results: A total of 171 patients were included. The mean age was 62.7±10.46 years and 40.9% (70) were female. Common primary malignancy types were lung (49), kidney (28), breast (25), and prostate (23). The average proximal and distal motor function difference was 0.38 (standard deviation=1.02, p<.0001) and 0.32 (standard deviation=0.91, p<.0001) respectively showing an improvement following surgery. Patients with proximal presurgical motor function of 2, 3, and 4 had an improved motor function in 73%, 77%, and 73% of the patients. Patients with distal presurgical motor function of 2, 3, and 4 had an improved motor function in 80%, 89%, and 70% of the patients. Conclusions: Most patients undergoing surgery for SMD have a modest improvement in motor function following surgery. The degree of improvement in most instances is less than 1 point on a 0 to 5 motor function scale. This is critical knowledge for a spinal surgeon when evaluating SMD patients with significant preoperative motor function deficits. These results aid spinal surgeons in setting expectations and evaluating the need for rapid spinal decompression.

[68Ga]Ga-DOTA-TATE uptake in subacute stroke following craniotomy for meningioma: a diagnostic tool for stroke?

Gallium 68 (68Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid labelled octreotate ([68Ga]Ga-DOTA-TATE) positron emission tomography (PET) is an established imaging technique for identifying tumours of neuroendocrine origin and meningiomas; the radiotracer binds to somatostatin receptor type 2 (SSTR2), which is richly expressed by these malignancies. Here, we present a rare case hinting at novel ischaemic stroke detection by [68Ga]Ga-DOTA-TATE PET scan. The scan was performed 14 days post resection of an atypical meningioma with the intention to assess the extent of residual tumour for radiosurgical treatment of the operative cavity. Surprisingly, the [68Ga]Ga-DOTA-TATE PET-avid region corresponded to an area of perioperative subacute ischaemic stroke detected by MRI. This case corroborates the two previously reported cases of incidental detection of ischaemic stroke during routine [68Ga]Ga-DOTA-TATE PET imaging, collectively suggesting the need for caution when interpreting the imaging findings. A possible underlying mechanism for [68Ga]Ga-DOTA-TATE uptake in stroke is increased SSTR2 expression by macrophages recruited into infarcted tissue.

Indolent nonendemic central nervous system histoplasmosis presenting as an isolated intramedullary enhancing spinal cord lesion.

BACKGROUND: Histoplasma capsulatum infection is largely seen in endemic regions; it results in symptomatic disease in <5% of those infected and is most often a self-limiting respiratory disease. Disseminated histoplasmosis is considered rare in the immunocompetent host. Central nervous system (CNS) dissemination can result in meningitis, encephalitis, and focal lesions in the brain and spinal cord, stroke, and hydrocephalus. An intramedullary spinal cord lesion as the only manifestation of CNS histoplasmosis has been rarely described. CASE DESCRIPTION: We present an atypical case of a 44-year-old man from a nonendemic region, on adalimumab therapy for ulcerative colitis who developed an isolated intramedullary spinal cord lesion in the setting of disseminated histoplasmosis. His course was initially indolent with vague systemic symptoms that led to consideration of several other diagnoses including sarcoidosis and lymphoma. Biopsies of several positron emission tomography positive lymph nodes revealed granulomatous inflammation, but no firm diagnosis was achieved. He was ultimately diagnosed with histoplasmosis after an acute respiratory infection in the setting of anti-tumor necrosis factor therapy. With appropriate antifungal therapy, the spinal cord lesion regressed. The previous systemic biopsies were re-reviewed, and rare fungal elements consistent with H. capsulatum were identified. A presumptive diagnosis of CNS histoplasmosis was made in the absence of direct laboratory confirmation in the setting of rapid and complete resolution on antifungal therapy. CONCLUSION: Disseminated histoplasmosis should be considered in granulomatous disease, even if the patient resides in a nonendemic region. Furthermore, clinicians should be mindful that CNS histoplasmosis may present in an atypical fashion.

Prospective prediction of clinical drug response in high-grade gliomas using an ex vivo 3D cell culture assay.

BACKGROUND: Clinical outcomes in high-grade glioma (HGG) have remained relatively unchanged over the last 3 decades with only modest increases in overall survival. Despite the validation of biomarkers to classify treatment response, most newly diagnosed (ND) patients receive the same treatment regimen. This study aimed to determine whether a prospective functional assay that provides a direct, live tumor cell-based drug response prediction specific for each patient could accurately predict clinical drug response prior to treatment. METHODS: A modified 3D cell culture assay was validated to establish baseline parameters including drug concentrations, timing, and reproducibility. Live tumor tissue from HGG patients were tested in the assay to establish response parameters. Clinical correlation was determined between prospective ex vivo response and clinical response in ND HGG patients enrolled in 3D-PREDICT (ClinicalTrials.gov Identifier: NCT03561207). Clinical case studies were examined for relapsed HGG patients enrolled on 3D-PREDICT, prospectively assayed for ex vivo drug response, and monitored for follow-up. RESULTS: Absent biomarker stratification, the test accurately predicted clinical response/nonresponse to temozolomide in 17/20 (85%, P = .007) ND patients within 7 days of their surgery, prior to treatment initiation. Test-predicted responders had a median overall survival post-surgery of 11.6 months compared to 5.9 months for test-predicted nonresponders (P = .0376). Case studies provided examples of the clinical utility of the assay predictions and their impact upon treatment decisions resulting in positive clinical outcomes. CONCLUSION: This study both validates the developed assay analytically and clinically and provides case studies of its implementation in clinical practice.

Case Report of a Primary Pituitary Abscess and Systematic Literature Review of Pituitary Abscess with a Focus on Patient Outcomes.

BACKGROUND: Pituitary abscess is a rare but potentially life-threatening condition with an incidence of 0.2%-1.1% of operative pituitary lesions. Diagnosis can be challenging, because this disorder shares many similarities with other pituitary lesions in terms of signs and symptoms and radiographic findings. Most pituitary abscesses are categorized as secondary, arising from preexisting pituitary lesions or in conjunction with transsphenoidal surgery, sepsis, meningitis, or sinusitis. There have been only a few reports of primary pituitary abscess, which occurs without any of the aforementioned risk factors. CASE DESCRIPTION: We present a case of primary pituitary abscess in a 38-year-old woman with headaches, blurry vision, polyuria, and polydipsia who was found to have hypopituitarism. Brain magnetic resonance imaging showed a sellar/suprasellar mass, which was endoscopically resected via a transsphenoidal approach. Egress of yellow-greenish creamy fluid was noted on dural incision. The patient was treated with a 6-week course of antibiotic therapy postoperatively and had resolution of symptoms. CONCLUSIONS: A PubMed search was performed; all cases of pituitary abscess reported in the literature were screened, and 200 cases including our case were analyzed with a focus on outcomes. The most common presentations were headache, visual disturbance, and endocrine abnormalities. Approximately 66.1% of patients achieved partial or complete recovery of pituitary function; 75.7% with vision deficits recovered visual function. Treatment via a craniotomy had a recurrence rate of 17.2% compared with 9.7% via a transsphenoidal approach. To our knowledge, this is the first systematic review on the topic and the largest series reported.

Association between trauma and acute hemorrhage of cavernous malformations in children: report of 3 cases.

OBJECTIVE Cavernous hemangiomas are benign congenital vascular abnormalities. Intracerebral cavernous hemangiomas have an appreciable risk of spontaneous hemorrhage. Little is known as to whether head trauma increases the risk of bleeding for these lesions. In this study, the authors present a case series of 3 patients with posttraumatic nonspontaneous hemorrhage of intracerebral cavernous malformations (CMs). For the first time, to the authors' knowledge, they propose that trauma might constitute a risk factor for acute hemorrhage in intracerebral cavernomas. METHODS The authors reviewed the charts of all patients with a new diagnosis of intracerebral cavernoma at their pediatric hospital between 2010 and 2014. Patients with a history of head trauma prior to presentation were subsequently studied to identify features common to these posttraumatic, hemorrhage-prone lesions. RESULTS A history of head trauma was identified in 3 of 19 cases. These 3 patients presented with seizures and/or headaches and were found to have acute hemorrhage within a cavernous hemangioma. None of these patients had any history of abnormal neurological symptoms. All 3 abnormal vascular lesions had associated developmental venous anomalies (DVAs). The 3 patients underwent resection of their respective vascular abnormalities, and the diagnosis of cavernous hemangioma was confirmed with postsurgical tissue pathology. All 3 patients had complete resolution of symptoms following complete excision of their lesions. CONCLUSIONS Trauma may represent a risk factor for acute hemorrhage in patients with CMs. The presence of associated DVAs may represent a risk factor for posttraumatic hemorrhage of cavernomas. Excision should be considered in such cases, if feasible.

Reversible changes in diffusion- and perfusion-based imaging in cerebral venous sinus thrombosis.

Diffusion- and perfusion-based imaging studies are regularly used in patients with ischemic stroke. Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke and is primarily treated by systemic anticoagulation. Endovascular intervention can be considered in cases of failed medical therapy, yet the prognostic value of diffusion- and perfusion-based imaging for CVST has not been clearly established. We present a patient with CVST whose abnormal findings on MRI and CT perfusion images were largely reversed after endovascular treatment.

Idiopathic Transverse Myelitis Mimicking an Intramedullary Spinal Cord Tumor.

The differential diagnoses for spinal cord lesions include spinal tumors and inflammatory processes. The distinction between these pathologies can be difficult if solely based on imaging. We report for the first time to our knowledge a case of idiopathic transverse myelitis (ITM) mimicking a discrete cervical spinal lesion in a 66-year-old man who presented with gait instability and neck pain. The patient's symptoms failed to resolve after an initial course of steroid therapy. Surgical biopsy confirmed the diagnosis of ITM. Subsequent treatment with dexamethasone resulted in complete resolution of the symptoms as well as the intramedullary enhancement. ITM is most common in the cervical and thoracic spine, spanning 3-4 spinal segments. It usually occupies more than 50% of the cross-sectional area of the spinal cord and tends to be central, uniform, and symmetric. It exhibits patchy and peripheral contrast enhancement. These criteria are useful guidelines that help distinguish ITM from neoplastic spinal lesions. A decision to perform biopsy must take into consideration the patient's clinical symptoms, the rate of progression of neurological deficits, and the imaging characteristics of the lesion. Surgical biopsy for questionable lesions should be reserved for patients with progressive neurological deficits refractory to empirical medical therapy.

Reversible changes in diffusion- and perfusion-based imaging in cerebral venous sinus thrombosis.

Diffusion- and perfusion-based imaging studies are regularly used in patients with ischemic stroke. Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke and is primarily treated by systemic anticoagulation. Endovascular intervention can be considered in cases of failed medical therapy, yet the prognostic value of diffusion- and perfusion-based imaging for CVST has not been clearly established. We present a patient with CVST whose abnormal findings on MRI and CT perfusion images were largely reversed after endovascular treatment.

The Impact of Preoperative Angiographic Identification of the Artery of Adamkiewicz on Surgical Decision Making in Patients Undergoing Thoracolumbar Corpectomy.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate the impact of spinal angiography on selection of surgical side in patients undergoing thoracolumbar corpectomy. SUMMARY OF BACKGROUND DATA: The artery of Adamkiewicz provides the major blood supply to the thoracolumbar spinal cord. Its location makes it vulnerable to injury during surgical procedures. Preoperative diagnostic spinal angiography is often used to determine the level and lateralization of the artery. METHODS: Data were gathered regarding level and laterality of the Adamkiewicz artery in 34 patients who underwent lateral extracavitary approaches to the thoracolumbar spine, preceded by diagnostic spinal angiography for localization of that artery. Two experienced spine surgeons were retrospectively polled regarding ideal side of approach for each case. This was compared with the actual side that was selected after angiographic localization. RESULTS: The artery was successfully identified in 71% of patients. The artery was most commonly located on the left side (83%) between T9 and L1 (83%). Diagnostic angiography seemed to have influenced surgical decision making in 54% of cases. In 21% of patients, there was no need to alter the side of approach. In the remaining 25%, the surgical plan was not altered on the basis of angiographic data, presumably due to anatomic limitations. No angiography- or surgery-related complications occurred in any of the patients. CONCLUSION: Preoperative spinal angiography seems to impact surgical decision making with regard to alteration of the side of approach in patients undergoing thoracolumbar corpectomy via lateral extracavitary approaches. LEVEL OF EVIDENCE: 4.

Neurolysis, neurectomy, and nerve repair/reconstruction for chronic pain.

Neuropathic pain may be a result of focal injury to a peripheral nerve. The treatment algorithm begins with nonoperative, then operative, options. In our practice, first-line surgical treatment should directly treat the injured nerve. Nerve decompression or neurolysis is useful in patients with entrapment syndromes and in cases where the course and/or the function of the nerve is altered by local scar or pathoanatomy. Neurectomy is an option in primary cases where numbness is an acceptable alternative to dysesthetic pain, or as an alternative following failed neurolysis. Nerve repair or reconstruction may improve pain by guiding axons past the neuroma.

Assessment of long-term kyphosis following transthoracic corpectomy with single adjacent level posterior instrumentation.

Anterior thoracic spinal instrumentation has traditionally been supported by a posterior thoracic construct spanning from at least two levels above to two levels below; however, instrumentation at a single-level above and below may be adequate to support such a construct. We report two cases of transthoracic corpectomy with short-segment posterior fixation with success in long-term stabilization. Two patients with thoracic vertebral malignancy resulting in spinal deformity and spinal cord compression underwent transthoracic corpectomy with placement of an expandable cage proceeded by posterior fixation one level above and one level below. Using the Cobb angle, the degree of kyphosis was measured at 3, 6, and 12 months postoperatively. Long-term spinal stabilization was achieved in both patients. There was no significant increase in kyphosis and no evidence of hardware failure in either patient during the follow-up period. Transthoracic corpectomy with supplementary posterior fixation one level above and below may be adequate to stabilize the spine.

Method for securing titanium cerebellar retractors.

BACKGROUND: Traditional stainless steel retractors can interfere with electromagnetic neuronavigation and intraoperative magnetic resonance imaging (ioMRI). In such cases, titanium instruments are frequently used; however, they often shift during the procedure. The authors describe a simple technique, illustrated with intraoperative photographs, for securing titanium cerebellar retractors into place to keep both the retractors and tissues in their desired locations throughout a craniotomy. METHODS: Titanium retractors were used by our institute's neurosurgical service during operations utilizing electromagnetic neuronavigation or ioMRI. Once the retractor was in the desired position, a 2-0 silk suture was placed around a retractor tong and tied outside the skin. Two sutures were placed on either side of the titanium retractor in the same fashion. RESULTS: Retractors were subsequently noted to remain in their desired position throughout the operative procedure. CONCLUSIONS: The authors describe a technique for securing titanium cerebellar retractors into their desired position during a craniotomy to minimize their movement during the procedure. This simple technique can help to eliminate a potential frequent source of surgeon frustration, and has proven to be quick to perform, safe, and practicable.