Michael Lim

Johns Hopkins Medicine | JHUSOM · Department of Neurosurgery

Objectives: In most cases of trigeminal neuralgia (TN), the trigeminal nerve is compressed by the arterial vasculature. We sought to address the current gap in understanding of pain outcomes in patients with sole arterial versus sole venous compression. Methods: We retrospectively reviewed all patients undergoing microvascular decompression at o...

STING-Type I interferon (IFN) signaling in myeloid cells plays a critical role in effective antitumor immune responses, but STING agonist as monotherapy has shown limited efficacy in clinical trials. The mechanisms that downregulate STING signaling are not fully understood. Here, we report that Protein phosphatase 2A (PP2A) with its specific B regu...

OBJECTIVE Pain outcomes by race in trigeminal neuralgia (TN) are not well investigated. The authors aimed to compare microvascular decompression (MVD) outcomes in TN patients on the basis of self-identified race. METHODS The authors retrospectively reviewed all patients with TN who underwent MVD at their institution from 2007 to 2020. Each patient...

Primary CNS neoplasms are responsible for considerable mortality and morbidity, and many therapies directed at primary brain tumors have proven unsuccessful despite their success in preclinical studies. Recently, the tumor immune microenvironment has emerged as a critical aspect of primary CNS neoplasms that may affect their malignancy, prognosis,...

Historically, the central nervous system (CNS) was considered an immune-privileged organ. However, recent studies have shown that the immune system plays a significant role in the CNS. Thus, there is renewed interest in applying cancer immunotherapy to CNS malignancies with the hope of generating a robust anti-tumor immune response and creating lon...

Background: Whether the total number of compressive vessels in trigeminal neuralgia (TN) affects outcomes after microvascular decompression (MVD) is unknown. Objective: To investigate whether the number of compressive vessels is associated with outcomes after MVD. Methods: We retrospectively reviewed all patients with TN who underwent MVDs at...

Background: Microvascular decompressions (MVDs) are effective open-surgical procedures for trigeminal neuralgia (TN). Intraoperative management of compressive veins may include either venous transposition or coagulation. Although both are generally considered safe, which technique results in optimal postoperative outcomes remains unclear. Objecti...

Background: Microvascular decompression (MVD) using a retrosigmoid approach is a highly effective, open-surgical procedure for neurovascular conflict in the posterior fossa, although there is a risk of postoperative cerebrospinal fluid (CSF) leak. Objective: To identify factors associated with postoperative CSF leakage after MVD. Methods: We r...

BACKGROUND GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment) is a biomarker based, multi-arm, international, seamless Phase 2/3 response adaptive randomization platform trial designed to rapidly identify experimental therapies that improve overall survival and confirm efficacious experimental therapies and associated biomar...

BACKGROUND: Craniectomies requiring skull reconstruction are indicated following oncological resection of masses involving the underlying brain and/or skull. Immediate cranioplasties have previously been performed using suboptimal hand-bending or molding techniques using ‘‘off – the – shelf’’ products. Today with computer – aided design, customized...

To ensure excellent postoperative clinical outcomes while preserving critical neurologic function, neurosurgeons who manage patients with intra-axial brain tumors can use intraoperative technologies and tools to achieve maximal safe resection. Neurosurgical oncology revolves around safe and optimal extent of resection, which further dictates subseq...

Purpose/Objective(s) Radiation immunodynamics, or the understanding of immune markers over a fractionated course of radiotherapy (RT), is a critical intermediate step in developing personalized RT approaches, including Immune-guided Radiotherapy (IM-GRT). Peripheral-origin myeloid cells are a major component of the glioblastoma (GBM) tumor microenv...

Purpose/Objective(s) To evaluate local control, overall survival, and toxicity profiles in patients with brain metastases aggressively treated with initial radiation followed by resection and aggressive re-irradiation upon pathological confirmation of failure of prior radiosurgery treatment. Materials/Methods A retrospective chart review identifie...

The purpose of this study was to evaluate the value of amide proton transfer‐weighted (APTw) MRI radiomic features for the differentiation of tumor recurrence from treatment effect in malignant gliomas. Eighty‐six patients who had suspected tumor recurrence after completion of chemoradiation or radiotherapy, and who had APTw‐MRI data acquired at 3T...

Objectives Effective therapies for acute pain management in trigeminal neuralgia (TN) are limited. Here, we investigate the role of steroids in TN patients experiencing acute pain flares. Methods We retrospectively reviewed patients presenting to the emergency room of a tertiary care institution between 2014-2020 for acute trigeminal neuralgia pai...

Introduction Preoperative MRI is a standard component of the preoperative clinical workup for patients prior to microvascular decompression (MVD). However, its ability to accurately exclude neurovascular compression of the trigeminal nerve is not well understood. Methods We retrospectively reviewed 1020 patients with available preoperative MRI dat...

Trigeminal neuralgia, historically dubbed the "suicide disease," is an exceedingly painful neurologic condition characterized by sudden episodes of intense facial pain. Unfortunately, the only U.S. Food and Drug Administration (FDA)-approved medication for trigeminal neuralgia carries substantial side effects, with many patients requiring surgery....

Background: Postoperative 30-day readmissions have been shown to negatively affect survival and other important outcomes in patients with glioblastoma (GBM). Objective: To further investigate patient readmission risk factors of primary and recurrent patients with GBM. Methods: The authors retrospectively reviewed records of 418 adult patients...

Objectives Microvascular decompression (MVD) has grown as a first-line surgical intervention for severe facial pain from trigeminal neuralgia and/or hemifacial spasm. We sought to examine the safety and cost-benefits of discharging MVD patients within one day of admission. Methods We retrospectively reviewed patients undergoing MVD at our institut...

The purpose of this study was to develop and verify a convolutional neural network (CNN)-based deep-learning algorithm to identify tumor progression versus response by adding amide proton transfer-weighted (APTw) MRI data to structural MR images as the proposed model input. 145 scans with 2175 MR instances from 98 patients with malignant glioma (ac...

Lesions within the brain cavity pose critical challenges for diagnostics, particularly distinction between cancerous and non-cancerous lesions. We here introduce an analytic technique called Real-CSF to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) f...

Glioblastoma is the most common primary malignant brain tumor and one of the most aggressive tumors across all cancer types with remarkable resistance to any treatment. While immunotherapy has shown a robust clinical benefit in systemic cancers, its benefit is still under investigation in brain cancers. The broader use of immunotherapy in clinical...

TPS2078 Background: GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment) is a biomarker based, multi-arm, international, seamless Phase 2/3 Response Adaptive Randomization platform trial designed to rapidly identify experimental therapies that improve overall survival and confirm efficacious experimental therapies and associat...

Background Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase 3 randomized CheckMate 548 study was to evaluate RT+TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed gl...

OBJECTIVE Internal neurolysis (IN) and intraoperative glycerin rhizotomy (ioGR) are emerging surgical options for patients with trigeminal neuralgia without neurovascular contact. The objective of this study was to compare the neurological outcomes of patients who underwent IN with those of patients who underwent ioGR. METHODS The authors retrospe...

Gliomas are the most common primary brain cancer. While it has been known that calcium-related genes correlate with gliomagenesis, the relationship between calcium-related genes and glioma prognosis remains unclear. We assessed TCGA datasets of mRNA expressions with differentially expressed genes (DEGs) and enrichment analysis to specifically scree...

Gliomas are intrinsic brain tumors that originate from glial cells. Glioblastoma (GBM) is the most aggressive glioma type and resistant to immunotherapy, mainly due to its unique immune environment. Dimensional data analysis reveals that the intra-tumoral heterogeneity of immune cell populations in the glioma microenvironment is largely made up of...

The antitumor activity of TIM-3 blocking antibodies has been investigated in preclinical models of cancer with promising results so far. Here we report in detail the first clinical experience with a human TIM-3 blocking antibody against high grade astrocytomas.

BACKGROUND Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in glioblastoma, but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase 3 CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO)+RT compared wit...

Background: Programmed death-ligand 1 (PD-L1) is upregulated in glioblastoma and supports immunosuppression. We evaluated PD-L1 blockade with durvalumab among glioblastoma cohorts and investigated potential biomarkers. Methods: MGMT unmethylated newly diagnosed patients received radiotherapy plus durvalumab (cohort A; n=40). Bevacizumab-naïve, r...

Background: The utility of arterial lines in microvascular decompression (MVD) is not well described. Objective: To examine the safety and costs of arterial lines compared with noninvasive blood pressure (NIBP) monitoring in MVDs. Methods: We retrospectively reviewed patients undergoing MVD from 2012 to 2020. Patients were grouped by procedure...

Background: Craniectomies requiring skull reconstruction are indicated following oncological resection of masses involving the underlying brain and/or skull. Immediate cranioplasties have previously been performed using suboptimal hand-bending or molding techniques using "off - the - shelf" products. Today with computer - aided design, customized...

Background The phase 1 cohorts (1c+1d) of CheckMate 143 (NCT02017717) evaluated the safety/tolerability and efficacy of nivolumab plus radiotherapy (RT) ± temozolomide (TMZ) in newly diagnosed glioblastoma. Methods In total, 136 patients were enrolled. In part A (safety lead-in), 31 patients (n=15, methylated/unknown MGMT promoter; n=16, unmethyla...

Due to their immunosuppressive role, tumor-infiltrating regulatory T cells (TI-Tregs) represent attractive therapeutic targets. Analysis of TI vs. peripheral Tregs (P-Tregs) from 36 patients, across four malignancies, identified 17 candidate Master Regulators (MRs), predicted to mechanistically regulate TI-Tregs transcriptional state. In vivo , poo...

Glioblastoma has emerged as an immunotherapy-refractory tumor based on negative phase III studies of anti-programmed cell death-1 therapy among newly diagnosed as well as recurrent patients. In addition, although much work on vaccine and cellular approaches is ongoing, therapeutic benefit with these approaches has been underwhelming. Much scientifi...

OBJECTIVE Subependymomas are low-grade ependymal tumors whose clinical characteristics, radiographic features, and postsurgical outcomes are incompletely characterized due to their rarity. The authors present an institutional case series and a systematic literature review to achieve a better understanding of subependymomas. METHODS Adult patients...

Several groups, including ours, have initiated efforts to develop small-animal irradiators that mimic radiation therapy (RT) for human treatment. The major image modality used to guide irradiation is cone-beam computed tomography (CBCT). While CBCT provides excellent guidance capability, it is less adept at localizing soft tissue targets growing in...

BACKGROUND Novel therapies are needed in newly diagnosed glioblastoma as nearly all patients experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ), including patients with tumors with methylated MGMT promoter, a positive prognostic factor and predictor of benefit with TMZ. Here, we report the final analysis of prog...

Purpose/Objective(s) The optimal timing of interval MRI surveillance following stereotactic radiosurgery (SRS) to detect most new lesions while asymptomatic and treatable by additional radiosurgery is unknown. As frequent MRI follow-up is an important patient burden and contributor to cost of care for brain metastases, we aimed to characterize the...

Meningioma is the most common primary CNS tumor in adults. Although most meningiomas can be benign and cured by surgical resection, there is a subset that can cause significant morbidity and mortality. While we normally associate the aggressive nature of these tumors with their grades, we have observed even refractory grade I meningiomas. Despite s...

Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engenders profound local and systemic immunosuppression an...

OBJECTIVE In this single-institution retrospective cohort study, the authors evaluated the effect of dexamethasone on postoperative complications and overall survival in patients with glioma undergoing resection. METHODS A total of 435 patients who underwent resection of a primary glioma were included in this retrospective cohort study. The inclus...

Clinical trials involving anti-programmed cell death protein-1 (anti-PD-1) failed to demonstrate improved overall survival in glioblastoma (GBM) patients. This may be due to the expression of alternative checkpoints such as B- and T- lymphocyte attenuator (BTLA) on several immune cell types including regulatory T cells. Murine GBM models indicate t...

Immune checkpoint inhibitors such as anti–programmed cell death protein 1 (anti-PD-1) have shown promise for the treatment of cancers such as melanoma, but results for glioblastoma (GBM) have been disappointing thus far. It has been suggested that GBM has multiple mechanisms of immunosuppression, indicating a need for combinatorial treatment strate...

Purpose To measure the value of early initial surveillance MRI scans in patients with brain metastases undergoing stereotactic radiosurgery (SRS), as MRI scans are a significant cost and patient stressor. Methods We identified a retrospective cohort of patients with brain metastases treated with SRS and followed at a single institution with schedu...

Objectives To describe toxicity and tumor outcome after resection and aggressive re-irradiation (stereotactic radiosurgery(SRS) or brachytherapy) of brain metastasis that have pathologically confirmed recurrence after prior radiosurgery. Methods A retrospective chart review identified 40 lesions in 35 patients that were initially treated with SRS,...

Purpose Widely-used CBCT-guided irradiators in pre-clinical radiation research are limited to localize soft tissue target due to low imaging contrast. Knowledge of target volume is a fundamental need for radiotherapy (RT). Without such information to guide radiation, normal tissue can be over-irradiated, introducing experimental uncertainties. It l...

BACKGROUND Gross total resection (GTR) of contrast-enhancing tumor is associated with increased survival in primary glioblastoma. Recently, there has been increasing interest in performing supratotal resections (SpTRs) for glioblastoma. OBJECTIVE To address the published results, which have varied in part due to lack of consensus on the definition...

Introduction Despite the advent of immunotherapy as a promising therapeutic, glioblastoma (GBM) remains resistant to using checkpoint blockade due to its highly immunosuppressive tumor milieu. Moreover, current anti-PD-1 treatment requires multiple infusions with adverse systemic effects. Therefore, we used a PCL:PEG:PCL polymer gel loaded with ant...

With rapid advances in our understanding of cancer, there is an expanding number of potential novel combination therapies, including novel–novel combinations. Identifying which combinations are appropriate and in which subpopulations are among the most difficult questions in medical research. We conducted a Preferred Reporting Items for Systematic...

OBJECTIVE International research fellows have been historically involved in academic neurosurgery in the United States (US). To date, the contribution of international research fellows has been underreported. Herein, the authors aimed to quantify the academic output of international research fellows in the Department of Neurosurgery at The Johns Ho...

Objective: To describe rates of cerebrospinal fluid (CSF) rhinorrhea after reconstruction of the IAC with calcium phosphate bone cement during retrosigmoid resections of vestibular schwannomas. Methods: A retrospective chart review of 177 patients who underwent retrosigmoid craniotomy and opening of the internal auditory canal for resection of a...

Objective: Non-small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined...

TPS2074 Background: GBM AGILE, Glioblastoma Adaptive, Global, Innovative Learning Environment, is an international, multi-arm, seamless phase 2/3 response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent glioblastoma (GBM) with the goal of identifying effective therapies matching th...

Background: Brain metastases are common in patients with breast cancer, and those with triple negative status have an even higher risk. Triple negative status is currently not considered when managing brain metastases. Objective: To determine whether triple negative breast cancer (TNBC) patients with brain metastases have a higher burden of intr...

IntroductionImmune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC an...

Introduction Despite recent advances in treatment for a number of cancers with immune checkpoint blockade (ICB), immunotherapy has had limited efficacy in glioblastoma (GBM). The recent multi-centered CheckMate 143 trial in first time recurrent GBM and the Checkmate 498 trial in newly diagnosed unmethylated GBM showed that antibodies against progra...

Meningiomas are slow-growing extraaxial tumors that account for about 25% of all intracranial tumors. The World Health Organization (WHO) classifies meningiomas as grade I, II, or III based upon morphologic criteria with higher grades correlating with more aggressive behavior such as local invasion, recurrence, and shortened survival. The main opti...

BACKGROUND Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options. OBJECTIVE To evaluate the role of programmed death-1 (PD-1) in cerebral vasospasm. METHODS Endovascular internal carotid artery perforation (ICAp) was used to induce cerebral vasospasm in mice. To evaluate the t...

Cancer immunotherapy has made remarkable advances with over fifty separate Food and Drug Administration (FDA) approvals as first or second line indications since 2015. These include immune checkpoint blocking antibodies, chimeric antigen receptor-transduced T-cells and bispecific T-cell-engaging antibodies. While multiple cancer types now benefit f...

Developing new therapies for patients with glioblastoma (GBM) requires focused interaction between industry, academia, nonprofits, patient advocacy, and health authorities, and novel approaches to clinical trials. GBM Adaptive Global Innovative Learning Environment (GBM AGILE) Trial was designed by over 130 global key opinion leaders in consultatio...

Dexamethasone is routinely administered to glioma patients for the management of cerebral edema. Dexamethasone is associated with significant side effects including hyperglycemia, increased risk of infection, and impaired anti-tumor immune response. Despite these risks, there are no standardized guidelines for the effective use of dexamethasone in...

Gross total resection (GTR) of contrast-enhancing tumor is associated with significantly increased overall survival in primary glioblastoma (GBM). Even when achieved, recurrence is likely, in part due to malignant cells infiltrating outside enhanced regions. Subsequently, there has been increasing interest in performing supratotal resections (SpTRs...

Brain metastasis is common in patients with breast cancer, and those with triple negative status have an even higher risk. Stereotactic radiosurgery (SRS) is preferred to whole brain radiation therapy (WBRT) in most patients. However, triple negative status is currently not considered when determining optimal radiation therapy. Given the aggressive...

Gliomas account for 30% of primary brain tumors and can frequently present with seizures. There are few guidelines for usage of anticonvulsant therapy in glioma patients. Some clinicians utilize anticonvulsant therapy in all glioma patients as a means of prophylaxis, whereas other clinicians prescribe anticonvulsant therapy only in patients that ex...

BACKGROUND Glioma associated myeloid cells (GAMs) can be induced to adopt an immunosuppressive phenotype that can lead to inhibition of anti-tumor responses in glioblastoma (GBM). Understanding the composition and phenotypes of GAMs is essential to modulating the myeloid compartment as a therapeutic adjunct to improve anti-tumor immune response. M...

Glioblastoma (GBM) is an aggressive primary tumor of the brain with a dismal prognosis for patients. Despite the standard of care treatment, median survival is 12–15 months. The blockade of inhibitory checkpoints such as PD-1 and CTLA-4 has become the mainstay immunotherapy to treat solid tumors but it lacks efficacy in treating GBM patients. Emerg...

Purpose of Review Immunotherapy has shown an unprecedented response in treatment of tumors. However, challenges such as lack of cytotoxic lymphocytes to mount an immune response or development of resistance to therapy can limit efficacy. Here, we discuss alternative checkpoints that can be targeted to improve cytotoxic lymphocyte function while har...

Although cone-beam CT (CBCT) has been used to guide irradiation for pre-clinical radiotherapy(RT) research, it is limited to localize soft tissue target especially in a low imaging contrast environment. Knowledge of target shape is a fundamental need for RT. Without such information to guide radiation, normal tissue can be irradiated unnecessarily,...

Glioma is the most common tumor in the central nervous system that portends a poor prognosis. Key genes negatively related to survival may provide targets for therapy to improve the outcome of glioma. Here, we report a protein-coding gene CLEC5A, which is the top 1 gene by univariate Cox regression analysis of 524 primary GBM samples. Expression of...

Usually recognized as transcripts of length more than 200 bp and devoid of open reading frames, long non-coding RNAs (lncRNAs) span a vast range of the human genome. Once thought to be of relatively little biological importance, they have been shown to be involved in many biological processes and diseases, highlighting their important regulatory fu...

There is an increasing interest in integrating immunotherapy with the current standard of care for primary and metastatic brain tumors, specifically with stereotactic radiosurgery. The abscopal effect has been described extensively in the literature, and preclinical studies suggest immunotherapy may synergize with radiation therapy for CNS tumors....

BACKGROUND The prognosis for brain metastasis is poor, and surgical resection is part of the standard of care for these patients as it has been shown to improve median overall survival. Development of neurological deficits after surgical resection has been associated with worsened outcomes in patients with glioblastoma. The effect of postoperative...