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Georg Neuloh and Johannes Schramm

Object. The aims of this study were to compare the efficiency of motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), and microvascular Doppler ultrasonography (MDU) in the detection of impending motor impairment from subcortical ischemia in aneurysm surgery; to determine their sensitivity for specific intraoperative events; and to compare their impact on the surgical strategy used.

Methods. Motor evoked potentials, SSEPs, and MDU were monitored during 100 operations for 129 aneurysms in 95 patients. Intraoperative events, monitoring results, and clinical outcome were correlated in a prospective observational design.

Motor evoked potentials indicated inadequate temporary clipping, inadvertent occlusion, inadequate retraction, vasospasm, or compromise to perforating vessels in 21 of 33 instances and deteriorated despite stable SSEPs in 18 cases. Microvascular Doppler ultrasonography revealed inadvertent vessel occlusion in eight of 10 cases and insufficient clipping in four of four cases. Stable evoked potentials (EPs) allowed safe, permanent vessel occlusion or narrowing despite reduced flow on MDU in five cases. Two patients sustained permanent and 10 showed transient new weakness, which had been detected by SSEPs in two of 12 patients and MEPs in 10 of 11 monitored cases. The surgical strategy was directly altered in 33 instances: by MEPs in 16, SSEPs in four, and MDU in 13.

Conclusions. Monitoring of MEPs is superior to SSEP monitoring and MDU in detecting motor impairment, particularly that from subcortical ischemia. Microvascular Doppler ultrasonography is superior to EP monitoring in detecting inadvertent vessel occlusion, but cannot assess remote collateral flow. Motor evoked potentials are most sensitive to all other intraoperative conditions and have a direct influence on the course of surgery in the majority of events. A controlled study design is required to confirm the positive effect of monitoring on clinical outcome in aneurysm surgery.

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Georg Neuloh, Ulrich Pechstein and Johannes Schramm

Object

Surgery for insular gliomas incurs a considerable risk of motor morbidity. In this study the authors explore the validity and utility of continuous motor tract monitoring to detect and reverse impending motor impairment during insular glioma resection.

Methods

Motor evoked potentials (MEPs) were successfully monitored during 73 operations to remove insular gliomas. Seventy-two cases were assessable, and one patient died during the early postoperative course. In this prospective observational approach, MEP monitoring results were correlated with intraoperative events and perioperative clinical data.

Intraoperative recordings of MEPs remained stable in 40 cases (56%), indicating unimpaired motor outcome and allowing safe completion of the hazardous steps of the procedure. Deterioration of MEPs occurred in 32 cases (44%). This deterioration was reversible after intervention in 21 cases (29%), and there was no new motor deficit except for transient paresis in nine of these cases (13%). Surgical measures could not prevent irreversible MEP deterioration in 11 cases (15%). Transient mild or moderate paresis occurred if complete MEP loss was avoided. Irreversible MEP loss in seven cases (10%) occurred after completion of resection in four of these seven cases, and was consistently an indicator of both a stroke within the deep motor pathways and permanent paresis, which remained severely disabling in three patients (4%). In contrast, permanently severe paresis occurred in two (18%) of 11 cases without useful MEP monitoring.

Conclusions

Continuous MEP monitoring is a valid indicator of motor pathway function during insular glioma surgery. This method indicates that remote ischemia, in this study the leading cause of impending motor deterioration, helps to avert definitive stroke of the motor pathways and permanent new paresis in the majority of cases. The rate of permanently severe new deficit appears to be greater in unmonitored cases.

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Rudolf A. Kristof, Maria Rother, Georg Neuloh and Dietrich Klingmüller

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.

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Matthias Simon, Georg Neuloh, Marec von Lehe, Bernhard Meyer and Johannes Schramm

Object

Treatment for insular (paralimbic) gliomas is controversial. In this report the authors summarize their experience with microsurgical resection of insular tumors.

Methods

The authors analyzed complications, functional outcomes, and survival in a series of 101 operations performed in 94 patients between 1995 and 2005.

Results

A > 90% resection was achieved in 42%, and 70–90% tumor removal was accomplished in 51% of cases. Functional outcomes varied considerably between patient subgroups. For example, in neurologically intact patients ≤ 40 years of age with WHO Grade I–III tumors, good outcomes (Karnofsky Performance Scale Score 80–100) were seen in 91% of cases. Predictors of an unfavorable functional outcome included histological features of glioblastoma, advanced age, and a low preoperative Karnofsky Performance Scale score. One year after surgery, 76% of patients who had presented with epilepsy were seizure free or experienced only isolated, nondebilitating seizures. Surprisingly good survival rates were seen after surgery for anaplastic gliomas. The median survival for patients with anaplastic astrocytomas (WHO Grade III) was 5 years, and the 5-year survival rate for those with anaplastic oligodendroglial tumors was 80%. Independent predictors of survival included younger age, favorable histological features (WHO Grade I and oligodendroglial tumors), Yaşargil Type 5A/B tumors with frontal extensions, and more extensive resections.

Conclusions

Insular tumor surgery carries substantial complication rates. However, surprisingly similar figures have been reported in large unselected craniotomy series and also after alternative treatment regimens. In view of the oncological benefits of resective surgery, our data would therefore argue for microsurgery as the primary treatment for most patients with a presumed WHO Grade I–III tumor. Patients with glioblastomas and/or age > 60 years require a more cautious approach.

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Rudolf A. Kristof, Georg Neuloh, Lioba Redel, Dietrich Klingmüller and Johannes Schramm

Object. The suppression of growth hormone (GH) to less than 1 µg/L during the oral glucose tolerance test (OGTT) is generally considered to be the standard for the assessment of biochemical remission of GH excess following surgery for GH-secreting pituitary adenomas. In this study the authors examine the reliability of the results of the early postoperative OGTT (epOGTT) in indicating remission or persistence of active acromegaly.

Methods. Data from the case files of 67 consecutive patients who underwent surgery for the first time for GH-secreting pituitary adenomas were reviewed retrospectively. Definitive remission of acromegaly was considered to be present if, without adjuvant therapy and at the most recent follow-up examination, GH was suppressed to less than 1 µg/L during the OGTT, the level of insulin-like growth factor—I (IGF-I) was within normal limits, and there was no clinical or magnetic resonance imaging evidence of persisting disease. The results of the epOGTT (obtained during the 2nd postoperative week) and the 3-month-postoperative OGTT (3mpOGTT) were compared with the patient's outcome at the most recent follow-up examination. A highly sensitive (≤ 0.3 µg/L) immunoradiometric assay for GH and a highly sensitive (≤ 32 µg/L) radioimmunoassay for IGF-I were used.

Correct epOGTT findings were noted in 83.6% of the patients: correct normal results (definitive remission of acromegaly) in 55.2% and correct pathological results (persisting acromegaly) in 28.3% of the patients. The rate of false findings was 16.4%: false normal results in 1.5% and false pathological results in 14.9% of the patients. The rate of correct 3mpOGTT findings increased to 98.5%: correct normal results in 68.6% and correct pathological ones in 29.8% of the patients. A false (false pathological) 3pmOGTT result occurred in only one patient (1.5%). At the most recent follow-up examinations (median 3.6 years) all OGTT findings were correct: correct normal results in 70.1% and correct pathological results in 29.9% of the patients. An intact adenopituitary function was associated (p = 0.04) with the occurrence of false epOGTT findings.

Conclusions. The high rate of false results, 16.4% for the epOGTT, declined significantly to 1.5% 3 months postoperatively and to 0% at the most recent follow-up examination. The OGTT appears to be more reliable at 3 months postoperatively. Unless there is obvious evidence of persisting disease following surgery for GH-secreting pituitary adenomas, adjuvant therapy should be delayed for 3 months postoperatively to avoid subjecting the patient to superfluous treatment.

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Andrea Szelényi, Lorenzo Bello, Hugues Duffau, Enrica Fava, Guenther C. Feigl, Miroslav Galanda, Georg Neuloh, Francesco Signorelli and Francesco Sala

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.

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Victor E. Staartjes, Morgan Broggi, Costanza Maria Zattra, Flavio Vasella, Julia Velz, Silvia Schiavolin, Carlo Serra, Jiri Bartek Jr., Alexander Fletcher-Sandersjöö, Petter Förander, Darius Kalasauskas, Mirjam Renovanz, Florian Ringel, Konstantin R. Brawanski, Johannes Kerschbaumer, Christian F. Freyschlag, Asgeir S. Jakola, Kristin Sjåvik, Ole Solheim, Bawarjan Schatlo, Alexandra Sachkova, Hans Christoph Bock, Abdelhalim Hussein, Veit Rohde, Marike L. D. Broekman, Claudine O. Nogarede, Cynthia M. C. Lemmens, Julius M. Kernbach, Georg Neuloh, Oliver Bozinov, Niklaus Krayenbühl, Johannes Sarnthein, Paolo Ferroli, Luca Regli, Martin N. Stienen and FEBNS

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.