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Introduction Brain tumors cause morbidity and mortality in part through peritumoral brain edema. The current main treatment for peritumoral brain edema are corticosteroids. Due to the increased recognition of their side-effect profile, there is growing interest in finding alternatives to steroids but there is little formal study of animal models of peritumoral brain edema. This study aims to summarize the available literature. Methods A systematic search was undertaken of 5 literature databases (Medline, Embase, CINAHL, PubMed and the Cochrane Library). The generic strategy was to search for various terms associated with “brain tumors”, “brain edema” and “animal models”. Results We identified 603 reports, of which 112 were identified as relevant for full text analysis that studied 114 peritumoral brain edema animal models. We found significant heterogeneity in the species and strain of tumor-bearing animals, tumor implantation method and edema assessment. Most models did not produce appreciable brain edema and did not test for observable manifestations thereof. Conclusion No animal model currently exists that enable the investigation of novel candidates for the treatment of peritumoral brain edema. With current interest in alternative treatments for peritumoral brain edema, there is an unmet need for clinically relevant animal models.

Background The interhemispheric fissure provides a natural surgical corridor to access tumors of the deep medial surface of the brain. Conventional microscopic approaches to these tumors are limited by the narrow width of the interhemispheric fissure and need for retraction of brain tissue or traversing overlying cortex. Over the last decade, the endoscope has been used to improve visualization of the operative field in neurosurgery, with benefits in terms of surgical ergonomics and extent of tumor resections. In the context of the interhemispheric fissure, an endoscopic approach may improve visualization of some tumors by providing a brighter, more divergent light source at depth and by enabling the operator to inspect around curved structures (e.g., corpus callosum). Case Description In this report, we present a series of 5 cases with tumors at various locations along the anteroposterior extent of the interhemispheric fissure that were resected using an endoscopic ipsilateral interhemispheric approach. Conclusions The endoscopic ipsilateral interhemispheric approach is an effective and versatile approach to resection of selected deep medial brain tumors extending anteriorly from the genu of the corpus callosum to the splenium. It has notable advantages over the microscope and can be considered a useful adjunct in the surgeon's armamentarium.

BackgroundIn recent years an increasing number of patients with cerebral metastasis (CM) have been referred to the neuro-oncology multidisciplinary team (NMDT). Our aim was to obtain a national picture of CM referrals to assess referral volume and quality and factors affecting NMDT decision making.MethodsA prospective multicenter cohort study including all adult patients referred to NMDT with 1 or more CM was conducted. Data were collected in neurosurgical units from November 2017 to February 2018. Demographics, primary disease, KPS, imaging, and treatment recommendation were entered into an online database.ResultsA total of 1048 patients were analyzed from 24 neurosurgical units. Median age was 65 years (range, 21-93 years) with a median number of 3 referrals (range, 1-17 referrals) per NMDT. The most common primary malignancies were lung (36.5%, n = 383), breast (18.4%, n = 193), and melanoma (12.0%, n = 126). A total of 51.6% (n = 541) of the referrals were for a solitary metastasis and resulted in specialist intervention being offered in 67.5% (n = 365) of cases. A total of 38.2% (n = 186) of patients being referred with multiple CMs were offered specialist treatment. NMDT decision making was associated with number of CMs, age, KPS, primary disease status, and extent of extracranial disease (univariate logistic regression, P < .001) as well as sentinel location and tumor histology (P < .05). A delay in reaching an NMDT decision was identified in 18.6% (n = 195) of cases.ConclusionsThis study demonstrates a changing landscape of metastasis management in the United Kingdom and Ireland, including a trend away from adjuvant whole-brain radiotherapy and specialist intervention being offered to a significant proportion of patients with multiple CMs. Poor quality or incomplete referrals cause delay in NMDT decision making.

OBJECTIVERaman spectroscopy is a biophotonic tool that can be used to differentiate between different tissue types. It is nondestructive and no sample preparation is required. The aim of this study was to evaluate the ability of Raman spectroscopy to differentiate between glioma and normal brain when using fresh biopsy samples and, in the case of glioblastomas, to compare the performance of Raman spectroscopy to predict the presence or absence of tumor with that of 5-aminolevulinic acid (5-ALA)–induced fluorescence.METHODSA principal component analysis (PCA)–fed linear discriminant analysis (LDA) machine learning predictive model was built using Raman spectra, acquired ex vivo, from fresh tissue samples of 62 patients with glioma and 11 glioma-free brain samples from individuals undergoing temporal lobectomy for epilepsy. This model was then used to classify Raman spectra from fresh biopsies from resection cavities after functional guided, supramaximal glioma resection. In cases of glioblastoma, 5-ALA–induced fluorescence at the resection cavity biopsy site was recorded, and this was compared with the Raman spectral model prediction for the presence of tumor.RESULTSThe PCA-LDA predictive model demonstrated 0.96 sensitivity, 0.99 specificity, and 0.99 accuracy for differentiating tumor from normal brain. Twenty-three resection cavity biopsies were taken from 8 patients after supramaximal resection (6 glioblastomas, 2 oligodendrogliomas). Raman spectroscopy showed 1.00 sensitivity, 1.00 specificity, and 1.00 accuracy for predicting tumor versus normal brain in these samples. In the glioblastoma cases, where 5-ALA–induced fluorescence was used, the performance of Raman spectroscopy was significantly better than the predictive value of 5-ALA–induced fluorescence, which showed 0.07 sensitivity, 1.00 specificity, and 0.24 accuracy (p = 0.0009).CONCLUSIONSRaman spectroscopy can accurately classify fresh tissue samples into tumor versus normal brain and is superior to 5-ALA–induced fluorescence. Raman spectroscopy could become an important intraoperative tool used in conjunction with 5-ALA–induced fluorescence to guide extent of resection in glioma surgery.

BackgroundChronic subdural hematoma (CSDH) is a common neurological condition; surgical evacuation is the mainstay of treatment for symptomatic patients. No clear evidence exists regarding the impact of timing of surgery on outcomes. We investigated factors influencing time to surgery and its impact on outcomes of interest.MethodsPatients with CSDH who underwent burr-hole craniostomy were included. This is a subset of data from a prospective observational study conducted in the UK. Logistic mixed modelling was performed to examine the factors influencing time to surgery. The impact of time to surgery on discharge modified Rankin Scale (mRS), complications, recurrence, length of stay and survival was investigated with multivariable logistic regression analysis.Results656 patients were included. Time to surgery ranged from 0 to 44 days (median 1, IQR 1–3). Older age, more favorable mRS on admission, high preoperative Glasgow Coma Scale score, use of antiplatelet medications, comorbidities and bilateral hematomas were associated with increased time to surgery. Time to surgery showed a significant positive association with length of stay; it was not associated with outcome, complication rate, reoperation rate, or survival on multivariable analysis. There was a trend for patients with time to surgery of ≥7 days to have lower odds of favorable outcome at discharge (p=0.061).ConclusionsThis study provides evidence that time to surgery does not substantially impact on outcomes following CSDH. However, increasing time to surgery is associated with increasing length of stay. These results should not encourage delaying operations for patients when they are clinically indicated.

Background The molecular genetic classification of gliomas, particularly the identification of isocitrate dehydrogenase (IDH) mutations, is critical for clinical and surgical decision-making. Raman spectroscopy probes the unique molecular vibrations of a sample to accurately characterize its molecular composition. No sample processing is required allowing for rapid analysis of tissue. The aim of this study was to evaluate the ability of Raman spectroscopy to rapidly identify the common molecular genetic subtypes of diffuse glioma in the neurosurgical setting using fresh biopsy tissue. In addition, classification models were built using cryosections, formalin-fixed paraffin-embedded (FFPE) sections and LN-18 (IDH-mutated and wild-type parental cell) glioma cell lines. Methods Fresh tissue, straight from neurosurgical theatres, underwent Raman analysis and classification into astrocytoma, IDH-wild-type; astrocytoma, IDH-mutant; or oligodendroglioma. The genetic subtype was confirmed on a parallel section using immunohistochemistry and targeted genetic sequencing. Results Fresh tissue samples from 62 patients were collected (36 astrocytoma, IDH-wild-type; 21 astrocytoma, IDH-mutated; 5 oligodendroglioma). A principal component analysis fed linear discriminant analysis classification model demonstrated 79%–94% sensitivity and 90%–100% specificity for predicting the 3 glioma genetic subtypes. For the prediction of IDH mutation alone, the model gave 91% sensitivity and 95% specificity. Seventy-nine cryosections, 120 FFPE samples, and LN18 cells were also successfully classified. Meantime for Raman data collection was 9.5 min in the fresh tissue samples, with the process from intraoperative biopsy to genetic classification taking under 15 min. Conclusion These data demonstrate that Raman spectroscopy can be used for the rapid, intraoperative, classification of gliomas into common genetic subtypes.

INTRODUCTION: Gross total resection (GTR), defined as complete resection of enhancing tumour on post-operative MRI, increases progression free survival (PFS) in patients with glioblastoma. We have extended the concept of functionally guided supramaximal resection (SMR) where the aim of surgery is to resect up to 2 cm beyond the enhancing tumour in all directions, limited only by functional boundaries. Boundaries are identified by pre-operative diffusion tensor imaging (DTI) scans, to estimate white matter fibre tract location, and awake craniotomy with cortical and subcortical stimulation. METHODS: Prospective non-randomised functionally guided surgical resection was undertaken in all IDH-wildtype glioblastomas undergoing primary surgical resection by the senior author between 2012–2017. Based on post-operative MRI scans, data on extent of tumour resection were analysed calculating tumour, brain and post resection volumes. Patients were then categorised into three different extent of resection groups: subtotal resection (STR), GTR, and SMR. All patients underwent post-operative radiotherapy and chemotherapy as per the Stupp protocol and were followed up with 3-monthly MRI scans. RESULTS: 69 cases of IDH-wildtype glioblastoma underwent resection within the timeframe. Survival data are currently available for 45 cases. The outcome measure is PFS, where progression is defined as recurrence of tumour. For actual treatment received, median PFS was 43.9 months (95% CI, 22.8–89.8 months) in the SMR group, 29.3 months (95% CI, 7.4–72.3 months) in GTR group and 13.3 months (95% CI, 10.3–27.6 months) in the STR group. The Kaplan-Meier survival curves of the three groups are clearly separated with no crossing. The logrank test indicates there is a significant difference (P value = 0.0003) between the survival curves of the three groups. There was no difference in the incidence of post-operative neurological deficit between the three groups. CONCLUSION: Supramaximal resection provides a significant increase in PFS compared to the current accepted standard of GTR.

Background There is an increasing drive to deliver a more efficient, cost-effective service leading to shorter stays in hospital. The advent of endoscopic and awake tumor surgery has reduced the morbidity associated with brain tumor resection, allowing patients to mobilize and be discharged earlier. Here, we present the outcomes from a single neurosurgical center in the United Kingdom on a fast track recovery program. Methods All consecutive patients undergoing elective endoscopic (n = 65) or awake (n = 10) tumor resection over a 3-year period between 1 December 2011 and 31 January 2015, under a single surgeon, were recruited. Data regarding their length of stay and outcomes were prospectively collated and analyzed. Results 66.7% of patients could be discharged safely within 1 postoperative day. Of the patients who stayed longer, 76% had a prolonged stay because of either social reasons or failing occupational therapy assessments. Only 6 cases (24%) of prolonged hospital admission were for medical reasons. Patients discharged within 1 day were no more likely to develop postoperative complications compared with those staying for longer (18% vs. 28%; odds ratio, 0.56; 95% confidence interval, 0.18–1.75; P = 0.21). The readmission rates were identical in both groups (16%). The only factor significantly affecting length of stay was World Health Organization performance score, both pre- and postoperative. Conclusions An early discharge after endoscopic and awake craniotomy tumor resection is both safe and feasible for most patients and is not associated with increased postoperative morbidity. We recommend that all patients who have good baseline function be offered short stay surgery.

Background Over the recent years an increasing number of patients with brain metastasis are being referred to the neuro-oncology multi-disciplinary team (NMDT). Our aim was to determine if referrals of this group of patients to the NMDT in the UK & Ireland comply with NICE guidelines and to assess referral volume, quality of information provided and its impact on NMDT decision-making. Methods Prospective multicentre oberservational study including all adult patients referred with ≥1 cerebral metastasis. Data was collected in neurosurgical units from 11/2017 to 02/2018. Demographics, primary disease, Karnofsky performance status (KPS), imaging and treatment recommendation were entered into an online database. Results 1049 patients were analysed from 24 neurosurgical units. Median age was 63[range 21–93] years with a median number of 3[range 1–17] referrals per NMDT. The most common primary malignancies were lung (36.5%, n=383), breast (18.5%, n=194) and melanoma (12.0%, n=126). 51.6% (n=541) of the referrals to the NMDT were within the NICE 2006 guidelines, and resulted in specialist intervention being offered in 68.8%. 41.2% (n=197) of patients being referred outside of the NICE 2006 guidelines were offered specialist treatment. NMDT decision-making was influenced by number of metastases, age, KPS, primary disease status and extent of extracranial disease (univariate logistic regression, p Conclusions This study confirmed a national change in culture of referral patterns. We identified a delay in NMDT decision-making in ~20%, contributing to increased NMDT workload. New stratification tools may be needed to reflect advancements in diagnostics and treatment modalities.

Objectives To determine the potential costs and health benefits of a serum-based spectroscopic triage tool for brain tumours, which could be developed to reduce diagnostic delays in the current clinical pathway. Design A model-based health pre-trial economic assessment. Decision tree models were constructed based on simplified diagnostic pathways. Models were populated with parameters identified from rapid reviews of the literature and clinical expert opinion. Setting Explored as a test in both primary and secondary care (neuroimaging) in the UK health service, as well as application to the USA. Participants Calculations based on an initial cohort of 10 000 patients. In primary care, it is estimated that the volume of tests would approach 75 000 per annum. The volume of tests in secondary care is estimated at 53 000 per annum. Main outcome measures The primary outcome measure was quality-adjusted life-years (QALY), which were employed to derive incremental cost-effectiveness ratios (ICER) in a cost-effectiveness analysis. Results Results indicate that using a blood-based spectroscopic test in both scenarios has the potential to be highly cost-effective in a health technology assessment agency decision-making process, as ICERs were well below standard threshold values of £20 000–£30 000 per QALY. This test may be cost-effective in both scenarios with test sensitivities and specificities as low as 80%; however, the price of the test would need to be lower (less than approximately £40). Conclusion Use of this test as triage tool in primary care has the potential to be both more effective and cost saving for the health service. In secondary care, this test would also be deemed more effective than the current diagnostic pathway.

Background Surgical access to the temporal lobe is complex with many eloquent white fiber tracts, requiring careful preoperative surgical planning. Many microsurgical approaches to the temporal lobes are described, each with their own disadvantages. The adoption of the endoscope in neurosurgery has increased the options available when treating these difficult access tumors. We present our experience of a novel, minimally invasive, endoscopic approach to resect temporal lobe tumors. Methods All patients undergoing endoscopic temporal lobe tumor resection between December 1, 2011 and December 1, 2017, with a single surgeon, were included. Tumors were resected through a minicraniotomy using a high-definition rigid endoscope with a 0- and 30-degree viewing angle. Bimanual resection was performed using standard microsurgical technique. Results There were 45 patients (22 men and 23 women) with a mean age of 53 years. There were 23 (51%) glioblastoma multiforme, 11 (24%) metastases, 7 (16%) astrocytoma, 3 (7%) anaplastic astrocytoma, and 1 (2%) World Health Organization grade I glioneuronal tumor. In 82.2% of cases (37/45), >95% resection was achieved and 42.2% (19/45) of patients achieving gross total resection. Conclusions The endoscope has a role in temporal lobe intraparenchymal tumor surgery, especially in 3 illustrative scenarios: 1) medial temporal, parahippocampal-gyrus low-grade nonenhancing gliomas, 2) subcortical high-grade glioma and metastases medial to the sagittal stratum, and 3) recurrent gliomas with cystic resection cavity. The endoscope offers a safe and useful adjunct to the surgeons' armamentarium in brain tumor surgery. A minimally invasive approach also reduces surgical morbidity and length of stay.

Image-guided brain biopsy is an established method to obtain histopathological diagnosis and guide management for cerebral lesions. The study aimed to establish negative biopsy and symptomatic haemorrhage rates at a single centre, and to assess the influence of factors such as lesion location, final pathology and the use of intra-operative smears.A retrospective analysis of all frame-based and frameless stereotactic biopsies carried out over 57 months from July 2006 to March 2011.A total of 351 biopsies were undertaken, 256 frame-based (73%) and 95 frameless (27%). Mean age was 57 years (range 18-87). Negative biopsy rate was 5.1%. There was a significantly greater negative biopsy rate in deep brain biopsies (p = 0.011) and in the cerebellum (p0.001). Intra-operative smear significantly reduced negative biopsy rates from 11.1% to 3.7% (p = 0.011). If repeat smear was requested, yet not provided, then the negative biopsy rate was 57.1% (p = 0.0085). The overall symptomatic haemorrhage rate was 3.7%. There was a significant increase in haemorrhage rate in deep versus superficial biopsies (p = 0.023) and a significantly greater haemorrhage rate in lymphoma biopsies (p = 0.015). There was no significant increase in haemorrhage rate in high-grade compared with low-grade tumour biopsies. Mortality rates at 7 and 30 days post-operatively were 0.6% and 1.7%, respectively, with mortality after 7 days unrelated to biopsy.We advocate intra-operative histopathological analysis to decrease negative biopsy rates and advise increased caution when undertaking biopsies of deep lesions or suspected lymphoma cases due to the potentially increased risk of haemorrhage.

BACKGROUND: Raman spectroscopy probes the unique molecular vibrations of a sample to accurately characterise its molecular composition. No sample processing is required allowing for rapid analysis of fresh tissue. The genetic classification of gliomas, particularly isocitrate dehydrogenase (IDH) mutations, is critical for clinical decision-making. With the development of new drugs targeting specific glioma genetic subtypes it will become increasingly important for surgeons to be aware of the genetics of the tumour at the time of operation to inform their surgical strategy. The aim of this study was to use Raman spectroscopy on fresh samples taken straight from the operating theatre and to classify gliomas according to their genetic subtypes. Similar classification models were built using cryosections and formalin-fix paraffin embedded (FFPE) sections. METHODS: Raman spectra were collected using a Renishaw benchtop RA800 series spectrometer. Parallel sections underwent immunohistochemistry with targeted genetic sequencing when required to confirm the following five glioma subtypes: glioblastoma, IDH-mutated; glioblastoma, IDH-wildtype; astrocytoma, IDH-mutated; astrocytoma, IDH-wildtype; oligodendroglioma. RESULTS: Fresh tissue samples from 62 patients were collected (9 glioblastoma, IDH-mutated; 35 glioblastoma, IDH-wildtype; 10 astrocytoma, IDH-mutated; 2 astrocytoma, IDH-wildtype; 5 oligodendroglioma, 1 excluded). A principal component-linear discriminant analysis (PCA-LDA) model demonstrated 80%-95% sensitivity and specificity for predicting the five glioma genetic subtypes. For prediction of IDH mutation alone the model gave a 92% sensitivity and 91% specificity. 86 cryosection and 117 FFPE samples underwent Raman with models demonstrating 87–94% sensitivity and 77–80% specificity for predicting IDH mutations. In the fresh tissue samples, the mean time for spectra collection was 9.5 minutes with the whole process from tumour biopsy to genetic classification taking under 30 minutes. CONCLUSION: These results demonstrate proof of concept that Raman spectroscopy can be used for rapid, intraoperative glioma genetic classification. Further work is being done to refine model building to increase classification performance.

INTRODUCTION: Raman spectroscopy is an emerging biophotonic tool for the identification of disease. By probing the unique molecular vibrations that depend on the composition and structure of samples, it provides a wealth of information on a cellular and molecular level of both solid and liquid specimens without the use of external agents such as dyes, stains or radioactive labels. Glioblastomas can be stratified by the presence or absence of mutations in isocitrate dehydrogenase (IDH) 1 or 2. Determination of IDH status is critical for histological diagnosis and clinical decision-making with evidence that the presence of IDH mutation confers better prognosis and a better response to chemotherapy. Mutation-positive tumours accumulate high concentrations of D-2-hydroxyglutarate, resulting in metabolic and epigenetic changes which we hypothesize will be reflected in a change in Raman scattering. In this study, we investigate the feasibility of using Raman spectroscopy to differentiate between IDH1 positive (IDH1+) and negative (IDH1-) tumours through classification modelling. METHOD: Forty biopsies of glioblastoma (WHO grade IV) in patients under the age of 40 years were classified into either IDH1+ (n=20) or IDH1- (n=20) using IDH-1(R132H) and BCAT-1 immunohistochemistry. 6µm thick sections were prepared from formalin fixed paraffin embedded specimens. Based on the hematoxylin and eosin stained contiguous section, high tumour density areas in the unstained sections were identified and subjected to analysis. Raman maps of ca. 1mm2 were acquired from up to two locations on each sample using an inVia Raman microscope (Renishaw, UK) configured with a 785nm excitation laser source. RESULTS: 30 spectral maps (60,325 spectra) from a total of 16 biopsy samples (8 IDH+ and 8 IDH-) have been collected to date. Principal component analysis (PCA) demonstrated good separation of the IDH1+ and IDH1- groups (see figure). A PCA-linear discriminant analysis classification model demonstrated 96.98% sensitivity and 90.1% specificity for predicting the presence of an IDH1 mutation. CONCLUSIONS: The results demonstrate the feasibility of using Raman spectroscopy to accurately distinguish IDH1 mutated glioblastomas from their IDH1- counterparts. Raman spectroscopy could provide a powerful tool to aid neuropathological diagnosis and genetic classification of glial tumours in the future.

Communicating hydrocephalus may complicate infantile bacterial meningitis, typically presenting with systemic features of infection. We report a rare case of ‘subclinical meningoventriculitis’ causing obstructive hydrocephalus and its challenging management. A healthy 10-week-old immunocompetent male patient presented with failure to thrive and vomiting, secondary to presumed gastro-oesophageal reflux. The child was neurologically alert, afebrile with normal inflammatory markers. Progressive macrocephaly prompted an MRI confirming triventricular hydrocephalus secondary to aqueductal stenosis. An endoscopic third ventriculostomy was performed however abandoned intraoperatively due to the unexpected finding of intraventricular purulent cerebrospinal fluid. A 6-week course of intravenous ceftriaxone was commenced for Escherichia coli meningoventriculitis. However, the child was readmitted 18 days postoperatively with acute hydrocephalus requiring a ventricular washout and staged ventriculoperitoneal shunt insertion at 4 weeks. Serial head circumference measurements are paramount in the assessment of a paediatric patient. In an immunocompetent child, a subclinical fibropurulent meningoventriculitis can result in several management challenges.

OBJECTIVE: To report a minimally invasive, nontubular endoscopic technique to resect intraparenchymal brain tumors and assess the feasibility, safety, and surgical resection margins achievable by this novel technique. METHODS: Over a 21-month period, 48 patients underwent 50 consecutive endoscopic intraparenchymal tumor resections. Data on surgical morbidity and mortality and length of stay were collected prospectively. The percentage of surgical resection and residual tumor volumes were calculated using preoperative and postoperative volume computed tomography or magnetic resonance imaging. All tumors were resected through a 2-cm minicraniotomy using a high-definition rigid endoscope with a 30-degree viewing angle. Bimanual resection was performed using standard microsurgical technique. RESULTS: Mean patient age was 53 years. There were 42 supratentorial (19 frontal, 17 temporal, 3 occipital, 1 parietal, and 2 parafalcine) tumors and 8 infratentorial tumors. Mean tumor volume was 41 cm(3). There were 12 metastases, 24 glioblastomas, 4 World Health Organization grade III gliomas, 5 World Health Organization grade I-II gliomas, 3 meningiomas, and 2 hemangioblastomas. On volumetric analysis, the overall mean percent resection was 96%. In 70% of cases, >95% resection was achieved; total resection was achieved in 48% of cases. At 30 days postoperatively, there was 1 new postoperative neurologic deficit; there were no deaths during this period. CONCLUSIONS: Our experience demonstrates that resection of intraparenchymal tumors using a minimally invasive endoscopic technique is technically feasible and safe, achieves good tumor resection margins, and has some potential advantages over a traditional microscopic technique.

Persistent anion conductances through GABAAreceptors (GABAARs) are important modulators of neuronal excitability. However, it is currently unknown how the amplitudes of these currents vary among different cell types in the human neocortex, particularly among diverse GABAergic interneurons. We have recorded 101 interneurons in and near layer 1 from cortical tissue surgically resected from both male and female patients, visualized 84 of them and measured tonic GABAAR currents in 48 cells with an intracellular [Cl–] of 65 mmand in the presence of 5 μmGABA. We compare these tonic currents among five groups of interneurons divided by firing properties and four types of interneuron defined by axonal distributions; rosehip, neurogliaform, stalked-bouton, layer 2–3 innervating and a pool of other cells. Interestingly, the rosehip cell, a type of interneuron only described thus far in human tissue, and layer 2–3 innervating cells exhibit larger tonic currents than other layer 1 interneurons, such as neurogliaform and stalked-bouton cells; the latter two groups showing no difference. The positive allosteric modulators of GABAARs allopregnanolone and DS2 also induced larger current shifts in the rosehip and layer 2–3 innervating cells, consistent with higher expression of the δ subunit of the GABAAR in these neurons. We have also examined how patient parameters, such as age, seizures, type of cancer and anticonvulsant treatment may alter tonic inhibitory currents in human neurons. The cell type-specific differences in tonic inhibitory currents could potentially be used to selectively modulate cortical circuitry.SIGNIFICANCE STATEMENTTonic currents through GABAAreceptors (GABAARs) are a potential therapeutic target for a number of neurologic and psychiatric conditions. Here, we show that these currents in human cerebral cortical GABAergic neurons display cell type-specific differences in their amplitudes which implies differential modulation of their excitability. Additionally, we examine whether the amplitudes of the tonic currents measured in our study show any differences between patient populations, finding some evidence that age, seizures, type of cancer, and anticonvulsant treatment may alter tonic inhibition in human tissue. These results advance our understanding of how pathology affects neuronal excitability and could potentially be used to selectively modulate cortical circuitry.