Meta-topologies define distinct anatomical classes of brain tumours linked to histology and survival.

The current World Health Organization classification integrates histological and molecular features of brain tumours. The aim of this study was to identify generalizable topological patterns with the potential to add an anatomical dimension to the classification of brain tumours. We applied non-negative matrix factorization as an unsupervised pattern discovery strategy to the fine-grained topographic tumour profiles of 936 patients with neuroepithelial tumours and brain metastases. From the anatomical features alone, this machine learning algorithm enabled the extraction of latent topological tumour patterns, termed meta-topologies. The optimal part-based representation was automatically determined in 10 000 split-half iterations. We further characterized each meta-topology's unique histopathologic profile and survival probability, thus linking important biological and clinical information to the underlying anatomical patterns. In neuroepithelial tumours, six meta-topologies were extracted, each detailing a transpallial pattern with distinct parenchymal and ventricular compositions. We identified one infratentorial, one allopallial, three neopallial (parieto-occipital, frontal, temporal) and one unisegmental meta-topology. Each meta-topology mapped to distinct histopathologic and molecular profiles. The unisegmental meta-topology showed the strongest anatomical-clinical link demonstrating a survival advantage in histologically identical tumours. Brain metastases separated to an infra- and supratentorial meta-topology with anatomical patterns highlighting their affinity to the cortico-subcortical boundary of arterial watershed areas.Using a novel data-driven approach, we identified generalizable topological patterns in both neuroepithelial tumours and brain metastases. Differences in the histopathologic profiles and prognosis of these anatomical tumour classes provide insights into the heterogeneity of tumour biology and might add to personalized clinical decision-making.

Choroidal artery ischemic events after temporal lobe epilepsy surgery: clinical outcome, quality of life, and surgical pitfalls.

OBJECTIVE: Ischemic events within the territory of the choroidal artery are an important cause of morbidity after temporal lobe epilepsy (TLE) surgery. The aim of the present study was to evaluate the rate of these ischemic events, their clinical presentation, and impact on patients' health-related quality of life (HRQoL) after TLE surgery. METHODS: Four hundred twenty-two consecutive patients undergoing temporal resections for drug-resistant TLE were retrospectively analyzed. All patients underwent presurgical multidisciplinary assessment using a standard protocol comprising clinical, neuroradiological, neuropsychological, and EEG data. Postoperative complications with corresponding imaging, neurological deficits, and disease-specific HRQoL questionnaires were evaluated. RESULTS: The overall complication rate was 7.8% (n = 33). Fourteen patients (3.3%) suffered from ischemic events causing 6 permanent motor deficits, 3 with permanent aphasias, and 6 visual field defects that exceeded quadrantanopia. In 8 patients with anterior choroidal artery infarction, accounting for 57% of all ischemic events, infarction volume correlated positively with the occurrence of new permanent neurological deficits (8666 vs 1692 mm3, p = 0.032). Despite the occurrence of ischemic events, HRQoL improved in 71% of patients. However, infarction volume showed a negative correlation trend with HRQoL (Pearson's r = -0.390, p = 0.094). There was a trend toward increased risk for ischemic events in patients who underwent selective amygdalohippocampectomy compared to patients who underwent anterior temporal lobectomy or temporal lesionectomy (RR 0.96, 95% CI 0.93-0.99, p = 0.08). CONCLUSIONS: Choroidal artery infarctions are rare but relevant complications after TLE surgery, presenting with variable clinical courses ranging from devastating neurological deterioration to complete recovery. Despite the occurrence of postoperative infarction, most patients report improvement of HRQoL after TLE surgery. This study showed that the type of surgery appears to modulate the risk for these ischemic events.

18F-FET-PET-guided gross total resection improves overall survival in patients with WHO grade III/IV glioma: moving towards a multimodal imaging-guided resection.

PURPOSE: PET using radiolabeled amino acid [18F]-fluoro-ethyl-L-tyrosine (FET-PET) is a well-established imaging modality for glioma diagnostics. The biological tumor volume (BTV) as depicted by FET-PET often differs in volume and location from tumor volume of contrast enhancement (CE) in MRI. Our aim was to investigate whether a gross total resection of BTVs defined as < 1 cm3 of residual BTV (PET GTR) correlates with better oncological outcome. METHODS: We retrospectively analyzed imaging and survival data from patients with primary and recurrent WHO grade III or IV gliomas who underwent FET-PET before surgical resection. Tumor overlap between FET-PET and CE was evaluated. Completeness of FET-PET resection (PET GTR) was calculated after superimposition and semi-automated segmentation of pre-operative FET-PET and postoperative MRI imaging. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. RESULTS: From 30 included patients, PET GTR was achieved in 20 patients. Patients with PET GTR showed improved median OS with 19.3 compared to 13.7 months for patients with residual FET uptake (p = 0.007; HR 0.3; 95% CI 0.12-0.76). This finding remained as independent prognostic factor after performing multivariate analysis (HR 0.19, 95% CI 0.06-0.62, p = 0.006). Other survival influencing factors such as age, IDH-mutation, MGMT promotor status, and adjuvant treatment modalities were equally distributed between both groups. CONCLUSION: Our results suggest that PET GTR improves the OS in patients with WHO grade III or IV gliomas. A multimodal imaging approach including FET-PET for surgical planning in newly diagnosed and recurrent tumors may improve the oncological outcome in glioma patients.

Adaptation of a semantic picture-word interference paradigm for future language mapping with transcranial magnetic stimulation: A behavioural study.

Neuro-navigated transcranial magnetic stimulation (TMS) helps to identify language-related cortical regions prior to brain tumour surgery. We adapted a semantic picture-word interference (PWI) paradigm from psycholinguistics to high-resolution TMS language mapping which prospectively can be used to specifically address the level of semantic processing. In PWI, pictures are presented along with distractor words which facilitate or inhibit the lexical access to the picture name. These modulatory effects of distractors can be annihilated in language-sensitive areas by the inhibitory effects of TMS on language processing. The rationale here is to observe the distractor effect without active stimulation and then to observe presumably its elimination by interference of the TMS stimulation. The special requirements to use PWI in this setting are (1) identifying word material for accelerating reliably naming latencies, choosing (2) the ideal presentation modality, and (3) the appropriate timing of distractor presentation. These are then controlled in real TMS language mapping. To adapt a semantic PWI naming paradigm for TMS application we employed 30 object-pictures in spoken German language. Part-whole associative semantic related or unrelated distractors were presented in two experiments including 15 healthy volunteers each, once auditorily and once visually. Data analysis across the entire stimulus set revealed a trend for facilitation in the visual condition, whereas no effects were observed for auditory distractors. In a sub-set, we found a significant facilitation effect for visual semantic distractors. Thus, with this study we provide a well-controlled item set for future studies implementing effective TMS language mapping applying visual semantic PWI.

The association of patient age with postoperative morbidity and mortality following resection of intracranial tumors.

Introduction: The postoperative functional status of patients with intracranial tumors is influenced by patient-specific factors, including age. Research question: This study aimed to elucidate the association between age and postoperative morbidity or mortality following the resection of brain tumors. Material and methods: A multicenter database was retrospectively reviewed. Functional status was assessed before and 3-6 months after tumor resection by the Karnofsky Performance Scale (KPS). Uni- and multivariable linear regression were used to estimate the association of age with postoperative change in KPS. Logistic regression models for a ≥10-point decline in KPS or mortality were built for patients ≥75 years. Results: The total sample of 4864 patients had a mean age of 56.4 â€‹± â€‹14.4 years. The mean change in pre-to postoperative KPS was -1.43. For each 1-year increase in patient age, the adjusted change in postoperative KPS was -0.11 (95% CI -0.14 - - 0.07). In multivariable analysis, patients ≥75 years had an odds ratio of 1.51 to experience postoperative functional decline (95%CI 1.21-1.88) and an odds ratio of 2.04 to die (95%CI 1.33-3.13), compared to younger patients. Discussion: Patients with intracranial tumors treated surgically showed a minor decline in their postoperative functional status. Age was associated with this decline in function, but only to a small extent. Conclusion: Patients ≥75 years were more likely to experience a clinically meaningful decline in function and about two times as likely to die within the first 6 months after surgery, compared to younger patients.

Quality of life in elderly patients after surgery for drug-resistant epilepsy - The impact of seizure outcome, neurological deficits and anxiety.

INTRODUCTION: Health related quality of life (HRQoL) has become a pivotal outcome parameter after surgery for drug-resistant epilepsy. The aim of the study was to investigate HRQoL and its relationship to seizure outcome, neurological deficits and anxiety after epilepsy surgery in a specific subpopulation of elderly patients. METHODS: A total of 85 elderly patients (older than 50 years) answered a standardized HRQoL questionnaire one year after epilepsy surgery. The questionnaire addressed the present self-assessed HRQoL in four subdomains (physical function, cognitive function, mood, social interaction). The questionnaire was based on the "Epilepsy Surgery Inventory-55", adapted for use in German speaking patients and validated by the QOLIE -10 and Beck Depression Inventory. RESULTS: A total of 51 patients (60%) were completely seizure free (ILAE1) at last available outcome (LAO). Permanent neurological deficits were observed in 8 patients (7%). Correlation analysis confirmed significant association between seizure outcome and overall HRQoL (r = -0.368, p < .001). New permanent neurological deficits showed impact on both HRQoL and the "cognitive function" subdomain. Anxiety and subjective assessment of postoperative status were strongly correlated with overall HRQoL (r = 0.692, p < .001 and r = 0.591, p < .001 respectively) and remained as independent prognostic factors in a multivariate regression analysis. CONCLUSION: Surgery for drug-resistant epilepsy in elderly improves patients' HRQoL. Both seizure freedom and new neurological deficits influence overall HRQoL. Interestingly, anxiety and patients' subjective assessment of postoperative status showed the highest impact on HRQoL in this subpopulation of epilepsy patients.

Development and external validation of a clinical prediction model for functional impairment after intracranial tumor surgery.

OBJECTIVE: Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient's risk of experiencing any functional impairment. METHODS: The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated. RESULTS: In the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69-0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69-0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/. CONCLUSIONS: Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.

Hemispheric Dominance for Language and Side Effects in Mapping the Inferior Frontal Junction Area with Transcranial Magnetic Stimulation.

BACKGROUND AND STUDY AIMS: Language mapping by navigated transcranial magnetic stimulation (TMS) is commonly applied over the left language-dominant hemisphere to indicate the language-related cortex. Detailed language mapping of Broca's region including stimulation targets in the immediate vicinity to the premotor cortex may raise concern about confounding unspecific motor effects. We performed interhemispheric comparisons to delineate such possible unspecific effects from true TMS-induced language inhibition. MATERIAL AND METHODS: Fifteen healthy German speakers named object pictures during navigated TMS over a left- and right-hemispheric target array covering the left inferior frontal junction area. Six mapping repetitions were conducted per hemisphere. Order of stimulation side was randomized between participants. Self-rating of discomfort was assessed after each stimulation; language errors and motor side effects were evaluated offline. RESULTS: Naming errors were observed significantly more frequently during left- than right-hemispheric stimulation. The same pattern was found for the most frequent error category of performance errors. Hierarchical cluster analyses of normalized ratings of error severity revealed a clear focus of TMS susceptibility for language inhibition in object naming at the dorsoposterior target sites only in the left hemisphere. We found no statistical difference in discomfort ratings between both hemispheres and also no interhemispheric difference in motor side effects, but we observed significantly stronger muscle contractions of the eyes as compared with the mouth. CONCLUSION: Our results of (1) unspecific pre-/motor effects similarly induced in both hemispheres, and (2) a specific focus of TMS susceptibility in the language-dominant hemisphere render any substantial contribution of nonlanguage-specific effects in TMS language mapping of the inferior frontal junction area highly unlikely.

Intraindividual comparison of selective intraarterial versus systemic intravenous 68Ga-DOTATATE PET/CT in patients with inoperable meningioma.

AIM: Here we describe the results of superselective intraarterial application of diagnostic Ga-68-DOTA0,Tyr3-octreotate (Ga-68-DOTATATE) in a series of patients with inoperable WHO grade II meningiomas which were no longer amenable to radiotherapy. METHODS: Four patients with inoperable WHO grade II meningioma underwent systemic venous infusion of Ga-68-DOTATATE followed by PET/CT. Ga-68-DOTATATE application was repeated intraarterially via transfemoral catheterization of vessels supplying the meningioma and another PET/CT was performed. RESULTS: Selective arterial infusion of Ga-68-DOTATATE increased the median value for the maximum standardized uptake value (SUV) by 2.6-fold (median venous: 7.1, median arterial: 21.6; range 2.0-5.0) and the median value for mean SUV by 2.7-fold (median venous: 4.3, median arterial: 11.2; range 1.6-5.6) compared to systemic intravenous infusion. Arterial application was well tolerated by all patients without complications. When compared to liver uptake, intravenous tracer uptake was insufficient for PRRT, whereas tracer uptake after superselective intraarterial tracer injection was sufficient to allow for peptide receptor radionuclide therapy (PRRT) in all patients. CONCLUSION: Insufficient tracer uptake in meningiomas after intravenous application of Ga-68-DOTATATE may be safely increased by a factor of 2-5 using transfemoral selective intraarterial tracer application.

Propofol Pharmacodynamics and Bispectral Index During Key Moments of Awake Craniotomy.

BACKGROUND: During awake craniotomy, the patient's language centers are identified by neurological testing requiring a fully awake and cooperative patient. Hence, anesthesia aims for an unconscious patient at the beginning and end of surgery but an awake and responsive patient in between. We investigated the plasma (Cplasma) and effect-site (Ceffect-site) propofol concentration as well as the related Bispectral Index (BIS) required for intraoperative return of consciousness and begin of neurological testing. MATERIALS AND METHODS: In 13 patients, arterial Cplasma were measured by high-pressure liquid chromatography and Ceffect-site was estimated based on the Marsh and Schnider pharmacokinetic/dynamic (pk/pd) models. The BIS, Cplasma and Ceffect-site were compared during the intraoperative awakening period at designated time points such as return of consciousness and start of the Boston Naming Test (neurological test). RESULTS: Return of consciousness occurred at a BIS of 77±7 (mean±SD) and a measured Cplasma of 1.2±0.4 µg/mL. The Marsh model predicted a significantly (P<0.001) higher Cplasma of 1.9±0.4 µg/mL as compared with the Schnider model (Cplasma=1.4±0.4 µg/mL) at return of consciousness. Neurological testing was possible as soon as the BIS had increased to 92±6 and measured Cplasma had decreased to 0.8±0.3 µg/mL. This translated into a time delay of 23±12 minutes between return of consciousness and begin of neurological testing. At begin of neurological testing, Cplasma according to Marsh (Cplasma=1.3±0.5 µg/mL) was significantly (P=0.002) higher as compared with the Schnider model (Cplasma=1.0±0.4 µg/mL). CONCLUSIONS: To perform intraoperative neurological testing, patients are required to be fully awake with plasma propofol concentrations as low as 0.8 µg/mL. Following our clinical setup, the Schnider pk/pd model estimates propofol concentrations significantly more accurate as compared with the Marsh model at this neurologically crucial time point.

Dissociated Crossed Speech Areas in a Tumour Patient.

In the past, the eloquent areas could be deliberately localised by the invasive Wada test. The very rare cases of dissociated crossed speech areas were accidentally found based on the clinical symptomatology. Today functional magnetic resonance imaging (fMRI)-based imaging can be employed to non-invasively localise the eloquent areas in brain tumour patients for therapy planning. A 41-year-old, left-handed man with a low-grade glioma in the left frontal operculum extending to the insular cortex, tension headaches, and anomic aphasia over 5 months underwent a pre-operative speech area localisation fMRI measurement, which revealed the evidence of the transhemispheric disposition, where the dominant Wernicke speech area is located on the left and the Broca's area is strongly lateralised to the right hemisphere. The outcome of the Wada test and the intraoperative cortico-subcortical stimulation mapping were congruent with this finding. After tumour removal, language area function was fully preserved. Upon the occurrence of brain tumours with a risk of impaired speech function, the rare dissociate crossed speech areas disposition may gain a clinically relevant meaning by allowing for more extended tumour removal. Hence, for its identification, diagnostics which take into account both brain hemispheres, such as fMRI, are recommended.

Comparison of propofol pharmacokinetic and pharmacodynamic models for awake craniotomy: A prospective observational study.

BACKGROUND: Anaesthesia for awake craniotomy aims for an unconscious patient at the beginning and end of surgery but a rapidly awakening and responsive patient during the awake period. Therefore, an accurate pharmacokinetic/pharmacodynamic (PK/PD) model for propofol is required to tailor depth of anaesthesia. OBJECTIVE: To compare the predictive performances of the Marsh and the Schnider PK/PD models during awake craniotomy. DESIGN: A prospective observational study. SETTING: Single university hospital from February 2009 to May 2010. PATIENTS: Twelve patients undergoing elective awake craniotomy for resection of brain tumour or epileptogenic areas. INTERVENTION: Arterial blood samples were drawn at intervals and the propofol plasma concentration was determined. MAIN OUTCOME MEASURES: The prediction error, bias [median prediction error (MDPE)] and inaccuracy [median absolute prediction error (MDAPE)] of the Marsh and the Schnider models were calculated. The secondary endpoint was the prediction probability PK, by which changes in the propofol effect-site concentration (as derived from simultaneous PK/PD modelling) predicted changes in anaesthetic depth (measured by the bispectral index). RESULTS: The Marsh model was associated with a significantly (P = 0.05) higher inaccuracy (MDAPE 28.9 ± 12.0%) than the Schnider model (MDAPE 21.5 ± 7.7%) and tended to reach a higher bias (MDPE Marsh -11.7 ± 14.3%, MDPE Schnider -5.4 ± 20.7%, P = 0.09). MDAPE was outside of accepted limits in six (Marsh model) and two (Schnider model) of 12 patients. The prediction probability was comparable between the Marsh (PK 0.798 ± 0.056) and the Schnider model (PK 0.787 ± 0.055), but after adjusting the models to each individual patient, the Schnider model achieved significantly higher prediction probabilities (PK 0.807 ± 0.056, P = 0.05). CONCLUSION: When using the 'asleep-awake-asleep' anaesthetic technique during awake craniotomy, we advocate using the PK/PD model proposed by Schnider. Due to considerable interindividual variation, additional monitoring of anaesthetic depth is recommended. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT 01128465.

Can in-vitro chemoresponse assays help find new treatment regimens for malignant gliomas?

Various in-vitro chemosensitivity and resistance assays (CSRAs) have been demonstrated to be helpful decision aids for non-neurological tumors. Here, we evaluated the performance characteristics of two CSRAs for glioblastoma (GB) cells. The chemoresponse of fresh GB cells from 30 patients was studied in vitro using the ATP tumor chemoresponse assay and the chemotherapy resistance assay (CTR-Test). Both assay platforms provided comparable results. Of seven different chemotherapeutic drugs and drug combinations tested in vitro, treosulfan plus cytarabine (TARA) was the most effective, followed by nimustine (ACNU) plus teniposide (VM26) and temozolomide (TMZ). Whereas ACNU/VM26 and TMZ have proven their clinical value for malignant gliomas in large randomized studies, TARA has not been successful in newly diagnosed gliomas. This seeming discrepancy between in vitro and clinical result might be explained by the pharmacological behavior of treosulfan. Our results show reasonable agreement between two cell-based CSRAs. They appear to confirm the clinical effectiveness of drugs used in GB treatment as long as pharmacological preconditions such as overcoming the blood-brain barrier are properly considered.

The common consensus criteria have high predictive values for long-term postoperative acromegaly remission.

OBJECTIVE: The aim of this work was to retrospectively study the long-term reliability of the common consensus endocrinological criteria for the assessment of postoperative remission of acromegaly. PATIENTS AND METHODS: In 96 consecutive patients, surgical remission of acromegaly following transsphenoidal surgery was considered to be present when, without adjuvant treatment, 3 months postoperatively there was no clinical evidence of persisting disease, and, according to the common consensus criteria for acromegaly remission, GH was suppressed to < 1 µg/l during the oral glucose tolerance test (OGTT) and insulin like growth factor-1 (IGF-1) was within normal limits. The results of the second postoperative week, 3 months postoperative, and the most recent follow-up OGTT and IGF-1 measurements were used to calculate the positive and negative predictive values of the following endocrinological criteria of acromegaly remission: the common consensus criteria for acromegaly remission, GH suppression to < 1 µg/l during OGTT and IGF-1 within normal limits. Sensitive IRMA (≤ 0.3 µg/l) and RIA (≤ 32 µg/l) assays for GH and IGF-1 were used. RESULTS: The surgical remission rate of acromegaly was 72.9%. At a median follow-up of 5.06 years, the recurrence rate of acromegaly was 2.08%. Overall, the common consensus criteria for acromegaly remission were the most reliable tests, with the following positive and negative predictive values at 2 weeks postoperatively, 3 months postoperatively and at the most recent follow-up: 68%, 100% and 100%, and 98%, 100% and 100%, respectively. The negative likelihood ratio confirmed that the test qualities of the common consensus criteria for acromegaly remission were superior to the other tests. CONCLUSIONS: The common consensus criteria were the most reliable tests for the diagnosis of postoperative acromegaly remission. The positive and negative predictive values of the common consensus criteria for acromegaly remission increased from the second postoperative week to 3 months postoperatively, thereafter reliably indicating the long-term results of transsphenoidal surgery.

Pre-existing chiasma syndromes do not entirely remit following transsphenoidal surgery for pituitary adenomas.

BACKGROUND: It is not known whether following transsphenoidal surgery for pituitary adenomas the vision of patients with preoperative chiasma syndromes (CS) does improve to the degree of vision of patients without preoperative CS. OBJECTIVE: The purpose of this study is to answer the question above. METHODS: Pertinent data of a successive series of patients operated transsphenoidally for the first time for pituitary adenoma were retrospectively analysed. RESULTS: Of the 304 patients, 35.1% presented preoperatively with CS. The median visual acuity (VA) of these patients improved significantly from preoperative (right eye, 0.63 (0; 1.25); left eye, 0.56 (0; 1.4)) to postoperative (right eye, 0.8 (0; 1.25); left eye, 0.74 (0; 1.25)). The median number of impaired quadrants of the binocular visual fields (VF) improved significantly from preoperative (2 (0; 8)) to postoperative CS (0 (0; 4)). In patients without preoperative CS, postoperative vision (VA as well as VF) remained unchanged. Postoperatively, VA of patients with preoperative CS remained significantly lower than that of patients without preoperative CS (right eye, 0.96 (0.2; 1.4); left eye, 0.94 (0.05; 1.4)). Postoperatively, the number of impaired quadrants of the binocular VF of patients with preoperative CS remained significantly higher than in patients without preoperative CS (0 (0; 1)). CONCLUSION: In this unselected patient series, the vision (VA as well as VF) of patients with preoperative CS did not improved postoperatively to the degree of the vision of patients without preoperative CS. Thus, in patients with adenomatous chiasma compression transsphenoidal surgery may be indicated before CS develops.

Functional impairments caused by chiasma syndromes prior to and following transsphenoidal pituitary adenoma surgery.

PURPOSE: To describe the functional impairment caused by chiasma syndromes (CS) prior to and following transsphenoidal pituitary adenoma surgery. METHODS: Pertinent data of a successive series of patients operated transsphenoidally for the first time for pituitary adenoma were retrospectively analyzed. The degree of functional impairment caused by the impairment of vision was quantified according to the resulting degree of disability (DOD). A DOD of > or =30 is considered substantial. RESULTS: None of the 197 of 304 (64.9%) patients without preoperative chiasma syndrome (CS) experienced postoperative worsening of their visual acuity or their visual fields. Thus, no change of their vision-related DOD (V-DOD) did occur. One hundred and seven (35.1%) of the patients presented preoperatively with CS. Postoperatively, 42.9% of the CS remitted completely, 38.3% improved, 11.2% remained unchanged, and 7.4% worsened. Accordingly, the median V-DOD improved significantly from 30 (0; 100) to 0 (0; 100). The prevalence of patients with V-DOD > or =30 dropped significantly from 51.4% preoperatively to 16.4% postoperatively. Postoperatively, the median V-DOD improved significantly up to 3 months postoperatively. Thereafter, no further significant changes occurred. However, in patients with preoperative CS, the median V-DOD as well as the prevalence of patients with a V-DOD > or =30 remained postoperatively significantly higher compared to patients without preoperative CS. CONCLUSIONS: Visual impairments due to CS frequently caused substantial DOD preoperatively. Postoperatively, the median degree of V-DOD as well as the prevalence of substantial V-DOD improved significantly. However, in patients with preoperative CS, V-DOD remained postoperatively significantly higher than V-DOD of patients without preoperative CS.

Continuous motor monitoring enhances functional preservation and seizure-free outcome in surgery for intractable focal epilepsy.

PURPOSE: Complete yet safe resection close to motor areas in medically intractable epilepsy requires functional information. New deficit may occur despite preservation of motor cortex, e.g., through vascular compromise. Here, we explore for the first time the feasibility, safety, and the clinical value of continuous motor-evoked potential (MEP) monitoring in focal epilepsy surgery. METHODS: High-frequency stimulation for MEP monitoring was performed during 100 consecutive lesionectomies critically related to motor areas and pathways. Extraoperative motor cortex mapping was performed in 27 of these cases via chronically implanted subdural grid electrodes. MEP monitoring results, postoperative motor outcome, and seizure control were correlated in a prospective observational design. RESULTS: Reliable MEP monitoring was achieved in 86 cases. Young age was the only discernible cause of unsuccessful recordings. Seizures from cortex stimulation did not occur. MEP changes (36%) predicted new motor deficit (17%) in all cases except purely cortical lesions. MEP changes predicted occurrence and permanence of new pareses. New deficit was significantly more frequent without (as compared with) successful monitoring (43% vs. 17%); permanently severe pareses from ischemia occurred only without MEPs (21% vs. 0%). Complete seizure control was significantly more frequent in successfully monitored cases (60% vs. 31%). Even with extraoperative motor mapping, severe paresis occurred only among cases with unsuccessful MEPs. CONCLUSIONS: Continuous MEP monitoring in epilepsy surgery is feasible and safe. It reflects motor function complementarily to the localizing motor mapping results. Successful MEP monitoring correlates with unimpaired motor outcome and full seizure control.

Intraoperative electrical stimulation in awake craniotomy: methodological aspects of current practice.

There is increasing evidence that the extent of tumor removal in low-grade glioma surgery is related to patient survival time. Thus, the goal of resecting the largest amount of tumor possible without leading to permanent neurological sequelae is a challenge for the neurosurgeon. Electrical stimulation of the brain to detect cortical and axonal areas involved in motor, language, and cognitive function and located within the tumor or along its boundaries has become an essential tool in combination with awake craniotomy. Based on a literature review, discussions within the European Low-Grade Glioma Group, and illustrative clinical experience, the authors of this paper provide an overview for neurosurgeons, neurophysiologists, linguists, and anesthesiologists as well as those new to the field about the stimulation techniques currently being used for mapping sensorimotor, language, and cognitive function in awake surgery for low-grade glioma. The paper is intended to help the understanding of these techniques and facilitate a comparison of results between users.

Incidence, clinical manifestations, and course of water and electrolyte metabolism disturbances following transsphenoidal pituitary adenoma surgery: a prospective observational study.

OBJECT: The authors prospectively studied the incidence, spectrum of clinical manifestations, course, and risk factors of water and electrolyte disturbances (WEDs) following transsphenoidal pituitary adenoma surgery. METHODS: From the preoperative day to the 14th postoperative day, 57 successive patients undergoing transsphenoidal adenomectomy were monitored daily for body weight, balance of fluids, serum electrolytes, plasma osmolality, plasma antidiuretic hormone (ADH) levels, urinary sodium excretion, urinary osmolality, and subjective sensation of thirst. The type of adenoma operated on and the intraoperative manipulation of the neurohypophysis were also recorded. RESULTS: Fifty-seven patients (mean age 55 years, 61.4% females) harbored 30 clinically hormone-inactive and 27 hormone-secreting pituitary adenomas. Postoperative WED occurred in 75.4% of the patients: in 38.5% as isolated diabetes insipidus (DI); in 21% as isolated hyponatremia; and in 15.7% as combined DI-hyponatremia. The maximum of medians of diuresis (5.750 L) in patients with isolated DI occurred on postoperative Day 2. Nadir of medians of hyponatremia (132 mmol/L) in patients with isolated hyponatremia occurred on postoperative Day 9. In patients with combined DI-hyponatremia, maximum of medians of diuresis (5.775 L) occurred on the 2nd day and nadir of medians of hyponatremia (130 mmol/L) on the 10th postoperative day. Altogether, 8.7% of the patients had to be treated with desmopressin because of DI persisting for >3 months. Of all the patients with hyponatremia, 42.8% were treated by transient fluid-intake restriction due to an IH of <130 mmol/L with or without clinical symptomatology. Transient acute renal failure occurred in one of these patients. Generally, the occurrence of postoperative WEDs was linked to the intraoperative manipulation of the neurohypophysis. Increased thirst correlated significantly with DI (p=0.001 and 0.02, respectively) and decreased thirst with the hyponatremic episode in patients with combined DI-hyponatremia (p=0.003). Decreased urine osmolality correlated significantly with the presence of DI (p=0.023). Electrolyte-free water clearance and urinary Na+ excretion were not correlated with DI and hyponatremia. Antidiuretic hormone was not suppressed during hyponatremia. CONCLUSIONS: Water and electrolyte disturbances occurred in the majority of patients undergoing transsphenoidal adenomectomy and were usually transient. Diabetes insipidus is more frequent than hyponatremia. Diabetes insipidus usually occurs during the 1st postoperative day and resolves in the majority of cases within 10 days. In few patients, DI may persist and require therapy with ADH analogs. Hyponatremia usually occurs at the end of the 1st postoperative week and resolves in most cases within 5 days. Very few patients will need treatment other than fluid-intake restriction to avoid serious complications. Thus, careful monitoring of the WEDs in patients undergoing transsphenoidal pituitary adenoma surgery is mandatory for the first 10 postoperative days.