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Sandeep Sood, Martin U. Schuhmann, Nedim Cakan, and Steven D. Ham

P The authors describe their experience with endoscopic fenestration of suprasellar cysts followed by shrinkage coagulation of the cysts to restore the anatomy in eight patients.

Seven children ranging in age from 8 months to 4.5 years and one adult 24 years of age were treated. Four of the children presented with megacephaly and the other patients with malfunction of a shunt that had been placed previously for hydrocephalus. Endoscopic fenestration of the cyst dome was performed followed by shrinkage of the lesion by means of endoscopic coagulation. Follow-up studies included immediate and late postoperative magnetic resonance imaging, assessment of growth velocity and the body mass index (BMI), and an endocrine profile if indicated by a failure of growth or precocious puberty.

Good intraoperative cyst shrinkage was achieved in all seven children. This was maintained on imaging studies at a mean follow-up period of 35 months. There was no significant procedure-associated morbidity. Hydrocephalus resolved in four patients who did not have a preexisting shunt. One of the four patients who had a shunt preoperatively became shunt free. The rest of the patients with preexisting shunts remained shunt dependent despite good resolution of the cyst. During a mean follow-up period of 52 months, the height, growth velocity, and BMI of each patient remained within two standard deviations of normal. In one patient there was a suspicion of precocious puberty, but the endocrine profile was normal; in another patient precocious puberty developed and required treatment.

The presented technique is safe and prevents cyst recurrence and obstruction of the aqueduct by remnants of the cyst wall—the two main reasons for failure of a simple endoscopic fenestration.

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Julian Zipfel, Juliane Engel, Konstantin Hockel, Ellen Heimberg, Martin U. Schuhmann, and Felix Neunhoeffer

OBJECTIVE

Hypertonic saline (HTS) is commonly used in children to lower intracranial pressure (ICP) after severe traumatic brain injury (sTBI). While ICP and cerebral perfusion pressure (CPP) correlate moderately to TBI outcome, indices of cerebrovascular autoregulation enhance the correlation of neuromonitoring data to neurological outcome. In this study, the authors sought to investigate the effect of HTS administration on ICP, CPP, and autoregulation in pediatric patients with sTBI.

METHODS

Twenty-eight pediatric patients with sTBI who were intubated and sedated were included. Blood pressure and ICP were actively managed according to the autoregulation index PRx (pressure relativity index to determine and maintain an optimal CPP [CPPopt]). In cases in which ICP was continuously > 20 mm Hg despite all other measures to decrease it, an infusion of 3% HTS was administered. The monitoring data of the first 6 hours after HTS administration were analyzed. The Glasgow Outcome Scale (GOS) score at the 3-month follow-up was used as the primary outcome measure, and patients were dichotomized into favorable (GOS score 4 or 5) and unfavorable (GOS score 1–3) groups.

RESULTS

The mean dose of HTS was 40 ml 3% NaCl. No significant difference in ICP and PRx was seen between groups at the HTS administration. ICP was lowered significantly in all children, with the effect lasting as long as 6 hours. The lowering of ICP was significantly greater and longer in children with a favorable outcome (p < 0.001); only this group showed significant improvement of autoregulatory capacity (p = 0.048). A newly established HTS response index clearly separated the outcome groups.

CONCLUSIONS

HTS significantly lowered ICP in all children after sTBI. This effect was significantly greater and longer-lasting in children with a favorable outcome. Moreover, HTS administration restored disturbed autoregulation only in the favorable outcome group. This highlights the role of a “rescuable” autoregulation regarding outcome, which might be a possible indicator of injury severity. The effect of HTS on autoregulation and other possible mechanisms should be further investigated.

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Kathrin Machetanz, Florian Grimm, Sophie Wang, Martin U. Schuhmann, Marcos Tatagiba, Alireza Gharabaghi, and Georgios Naros

OBJECTIVE

Conventional frame-based stereotaxy through a transfrontal approach (TFA) is the gold standard in brainstem biopsies. Because of the high surgical morbidity and limited impact on therapy, brainstem biopsies are controversial. The introduction of robot-assisted stereotaxy potentially improves the risk-benefit ratio by simplifying a transcerebellar approach (TCA). The aim of this single-center cohort study was to evaluate the risk-benefit ratio of transcerebellar brainstem biopsies performed by 2 different robotic systems. In addition to standard quality indicators, a special focus was set on trajectory selection for reducing surgical morbidity.

METHODS

This study included 25 pediatric (n = 7) and adult (n = 18) patients who underwent 26 robot-assisted biopsies via a TCA. The diagnostic yield, complication rate, trajectory characteristics (i.e., length, anatomical entry, and target-point location), and skin-to-skin (STS) time were evaluated. Transcerebellar and hypothetical transfrontal trajectories were reconstructed and transferred into a common MR space for further comparison with anatomical atlases.

RESULTS

Robot-assisted, transcerebellar biopsies demonstrated a high diagnostic yield (96.2%) while exerting no surgical mortality and no permanent morbidity in both pediatric and adult patients. Only 3.8% of cases involved a transient neurological deterioration. Transcerebellar trajectories had a length of 48.4 ± 7.3 mm using a wide stereotactic corridor via crus I or II of the cerebellum and the middle cerebellar peduncle. The mean STS time was 49.5 ± 23.7 minutes and differed significantly between the robotic systems (p = 0.017). The TFA was characterized by longer trajectories (107.4 ± 11.8 mm, p < 0.001) and affected multiple eloquent structures. Transfrontal target points were located significantly more medial (−3.4 ± 7.2 mm, p = 0.042) and anterior (−3.9 ± 8.4 mm, p = 0.048) in comparison with the transcerebellar trajectories.

CONCLUSIONS

Robot-assisted, transcerebellar stereotaxy can improve the risk-benefit ratio of brainstem biopsies by avoiding the restrictions of a TFA and conventional frame-based stereotaxy. Profound registration and anatomical-functional trajectory selection were essential to reduce mortality and morbidity.

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Martin U. Schuhmann, Kimberly R. Ostrowski, Emily J. Draper, Jau-Wen Chu, Steven D. Ham, Sandeep Sood, and James P. McAllister

Object

Shunt infections and their management remain a clinically important problem in patients with hydrocephalus. The authors evaluated, in comparison with traditional parameters, C-reactive protein (CRP) in blood/serum (S-CRP) and in cerebrospinal fluid (CSF; C-CRP) for its power to identify and treat patients with infected shunts.

Methods

On 84 different occasions, CSF and blood samples from 59 children suspected of having shunt/CSF infections were obtained and evaluated. An infection was proven by a CSF culture in 35 of 84 evaluations. Values for S-CRP in infected individuals were higher than in noninfected ones (91.8 ± 70.2 mg/L compared with 16.1 ± 28.3 mg/L, p < 0.0001). The sensitivity of S-CRP testing was 97.1%, the specificity 73.5%, the negative predictive value 97.3%, and the receiver operating characteristic area 91.6%. The probability of shunt/CSF infection—provided that the S-CRP level was greater than 7 mg/L—rose from 41.7% (prevalence) to a posttest level of 72.3%. Specificity and posttest probability were 87.8 and 87.2%, respectively, if cases with other concurrent infections were excluded. The probability of missing a CSF/shunt infection at an S-CRP lower than 7 mg/L was 2.7%. All other diagnostic parameters did not yield useful test results. The rate of reinfection was elevated in patients in whom S-CRP levels were greater than 7 mg/L at the time of shunt reimplantation.

Conclusions

Analysis of these data suggests that the S-CRP level should be included in the first-line workup of patients with suspected shunt/CSF infection. It seems justified to avoid performing a shunt tap if S-CRP levels are less than 7 mg/L. A larger multicenter trial is necessary to confirm these promising diagnostic results and to deliver hard data concerning whether or not a normalized S-CRP level is a reliable indicator of successful antibiotic therapy and whether a shunt can be safely reimplanted.

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Sandeep Sood, Cherukuri Ravi Kumar, Mohammad Jamous, Martin U. Schuhmann, Steven D. Ham, and Alexa I. Canady

Object. Patients undergoing long-term shunt therapy following shunt malfunction often present with acute neurological deterioration, high intracranial pressure (ICP), and yet small or slit ventricles. It is believed that low brain compliance prevents ventricle enlargement in such cases. To elucidate the underlying pathophysiology, the authors estimated compliance as a function of cerebrovascular distensibility in 45 patients undergoing chronic shunt therapy.

Methods. The ICP and pressure—volume index (PVI) were measured at end-tidal CO2 of 30 mm Hg (PVI30) and 40 mm Hg (PVI40). The ventricle volume was dichotomized as slit/small/normal or dilated based on the frontooccipital horn ratio. In 18 patients PVI30 was normal (18.4 ± 4 ml), whereas in 27 patients it was significantly elevated (45.5 ± 14 ml). Clinical symptoms or ventricle size at presentation did not correlate with the PVI30. The ICP and PVI at end-tidal CO2 of 40 mm Hg were significantly higher than those at end-tidal CO2 of 30 mm Hg (p < 0.001 and < 0.02, respectively) suggesting an increased cerebrovascular distensibility.

Conclusions. The authors did not observe a low compliance in patients undergoing chronic shunt therapy who, at shunt malfunction, presented with a slit/small/normal ventricle; however, analysis of the findings strongly indicated that an increased cerebrovascular distensibility was present in these patients. This may explain the high ICP and acute clinical deterioration following shunt malfunction in such cases.

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Constantin Roder, Martin Breitkopf, MS, Sotirios Bisdas, Rousinelle da Silva Freitas, Artemisia Dimostheni, Martin Ebinger, Markus Wolff, Marcos Tatagiba, and Martin U. Schuhmann

OBJECTIVE

Intraoperative MRI (iMRI) is assumed to safely improve the extent of resection (EOR) in patients with gliomas. This study focuses on advantages of this imaging technology in elective low-grade glioma (LGG) surgery in pediatric patients.

METHODS

The surgical results of conventional and 1.5-T iMRI-guided elective LGG surgery in pediatric patients were retrospectively compared. Tumor volumes, general clinical data, EOR according to reference radiology assessment, and progression-free survival (PFS) were analyzed.

RESULTS

Sixty-five patients were included in the study, of whom 34 had undergone conventional surgery before the iMRI unit opened (pre-iMRI period) and 31 had undergone surgery with iMRI guidance (iMRI period). Perioperative data were comparable between the 2 cohorts, apart from larger preoperative tumor volumes in the pre-iMRI period, a difference without statistical significance, and (as expected) significantly longer surgeries in the iMRI group. According to 3-month postoperative MRI studies, an intended complete resection (CR) was achieved in 41% (12 of 29) of the patients in the pre-iMRI period and in 71% (17 of 24) of those in the iMRI period (p = 0.05). Of those cases in which the surgeon was postoperatively convinced that he had successfully achieved CR, this proved to be true in only 50% of cases in the pre-iMRI period but in 81% of cases in the iMRI period (p = 0.055). Residual tumor volumes on 3-month postoperative MRI were significantly smaller in the iMRI cohort (p < 0.03). By continuing the resection of residual tumor after the intraoperative scan (when the surgeon assumed that he had achieved CR), the rate of CR was increased from 30% at the time of the scan to 85% at the 3-month postoperative MRI.

The mean follow-up for the entire study cohort was 36.9 months (3–79 months). Progression-free survival after surgery was noticeably better for the entire iMRI cohort and in iMRI patients with postoperatively assumed CR, but did not quite reach statistical significance. Moreover, PFS was highly significantly better in patients with CRs than in those with incomplete resections (p < 0.001).

CONCLUSIONS

Significantly better surgical results (CR) and PFS were achieved after using iMRI in patients in whom total resections were intended. Therefore, the use of high-field iMRI is strongly recommended for electively planned LGG resections in pediatric patients.

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Rainer Ritz, Guenther C. Feigl, Martin U. Schuhmann, André Ehrhardt, Soeren Danz, Susan Noell, Antje Bornemann, and Marcos S. Tatagiba

The introduction of fluorescence-guided resection of primary malignant brain tumors was a milestone in neurosurgery. Deep-seated malignant brain tumors are often not approachable for microsurgical resection. For diagnosis and therapy, new strategies are recommended. The combination of endoscopy and 5-aminolevulinic acid–induced protoporphyrin IX (5-ALA-induced Pp IX) fluorescence–guided procedures supported by neuronavigation seems an interesting option. Here the authors report on a combined approach for 5-ALA fluorescence–guided biopsy in which they use an endoscopy system based on an Xe lamp (excitation approximately λ = 407 nm; dichroic filter system λ = 380–430 nm) to treat a malignant tumor of the thalamus and perform a ventriculostomy and septostomy. The excitation filter and emission filter are adapted to ensure that the remaining visible blue remission is sufficient to superimpose on or suppress the excited red fluorescence of the endogenous fluorochromes. The authors report that the lesion was easily detectable in the fluorescence mode and that biopsy led to histological diagnosis.

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Bart Depreitere, Fabian Güiza, Greet Van den Berghe, Martin U. Schuhmann, Gottlieb Maier, Ian Piper, and Geert Meyfroidt

Object

In severe traumatic brain injury, a universal target for cerebral perfusion pressure (CPP) has been abandoned. Attempts to identify a dynamic CPP target based on the patient's cerebrovascular autoregulatory capacity have been promising so far. Bedside monitoring of pressure autoregulatory capacity has become possible by a number of methods, Czosnyka's pressure reactivity index (PRx) being the most frequently used. The PRx is calculated as the moving correlation coefficient between 40 consecutive 5-second averages of intracranial pressure (ICP) and mean arterial blood pressure (MABP) values. Plotting PRx against CPP produces a U-shaped curve in roughly two-thirds of monitoring time, with the bottom of this curve representing a CPP range corresponding with optimal autoregulatory capacity (CPPopt). In retrospective series, keeping CPP close to CPPopt corresponded with better outcomes. Monitoring of PRx requires high-frequency signal processing. The aim of the present study is to investigate how the processing of the information on cerebrovascular pressure reactivity that can be obtained from routine minute-by-minute ICP and MABP data can be enhanced to enable CPPopt recommendations that do not differ from those obtained by the PRx method, show the same associations with outcome, and can be generated in more than two-thirds of monitoring time.

Methods

The low-frequency autoregulation index (LAx) was defined as the moving minute-by-minute ICP/MABP correlation coefficient calculated over time intervals varying from 3 to 120 minutes. The CPPopt calculation was based on LAx-CPP plots and done for time windows between 1 and 24 hours and for each LAx type. The resulting matrix of CPPopts were then averaged in a weighted manner, with the weight based on the goodness of fit of a U-shape and the lower value of the LAx corresponding to the U-bottom, to result in a final CPPopt recommendation. The association between actual CPP/CPPopt and outcome was assessed in the multicenter Brain Monitoring with Information Technology Research Group (BrainIT) database (n = 180). In the Leuven-Tübingen database (60-Hz waveform data, n = 21), LAx- and PRx-based CPPopts were compared.

Results

In the BrainIT database, CPPopt recommendations were generated in 95% of monitoring time. Actual CPP being close to LAx-based CPPopt was associated with increased survival. In a multivariate model using the Corticosteroid Randomization After Significant Head Injury (CRASH) model as covariates, the average absolute difference between actual CPP and CPPopt was independently associated with increased mortality. In the high-frequency data set no significant difference was observed between PRx-based and LAx-based CPPopts. The new method issued a CPPopt recommendation in 97% of monitoring time, as opposed to 44% for PRx-based CPPopt.

Conclusions

Minute-by-minute ICP/MABP data contain relevant information for autoregulation monitoring. In this study, the authors' new method based on minute-by-minute data resolution allowed for CPPopt calculation in nearly the entire monitoring time. This will facilitate the use of pressure reactivity monitoring in all ICUs.

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Ulrich-Wilhelm Thomale, Astrid K. Gnekow, Daniela Kandels, Brigitte Bison, Pablo Hernáiz Driever, Olaf Witt, Torsten Pietsch, Arend Koch, David Capper, Rolf-Dieter Kortmann, Beate Timmermann, Semi Harrabi, Michèle Simon, Ahmed El Damaty, Juergen Krauss, Martin U. Schuhmann, and Annette Aigner

OBJECTIVE

Neurosurgical treatment is an integral part of the treatment algorithms for pediatric low-grade glioma (LGG), yet patterns of surgical procedures are rarely challenged. The objective of this study was to evaluate surgical treatment patterns in pediatric LGG.

METHODS

The German Societé Internationale d’Oncologie Pédiatrique (SIOP)–LGG 2004 cohort was analyzed to identify relevant patient and tumor characteristics associated with time to death, next surgery, number of resections, and radiological outcome.

RESULTS

A total of 1271 patients underwent 1713 neurosurgical interventions (1 intervention in 947, 2 in 230, 3 in 70, and 4–6 in 24). The median age of the study population was 8.57 years at first surgery, and 46.1% were female. Neurofibromatosis type 1 (NF1) was found in 4.4%, and 5.4% had tumor dissemination. Three hundred fifty-four patients (27.9%) had chemotherapy and/or radiotherapy. The cumulative incidence of second surgery at 10 years was 26%, and was higher for infants, those with spinal and supratentorial midline (SML) tumors, and those with pilomyxoid astrocytomas. The hazard ratio for subsequent surgery was higher given dissemination and noncomplete initial resection, and lower for caudal brainstem and SML tumors. Among 1225 patients with fully documented surgical records and radiological outcome, 613 reached complete remission during the observation period, and 50 patients died. Patients with pilocytic astrocytoma had higher chances for a final complete remission, whereas patients with initial partial or subtotal tumor resection, dissemination, NF1, or primary tumor sites in the spinal cord and SML had lower chances.

CONCLUSIONS

Neurosurgery is a key element of pediatric LGG treatment. In almost 50% of the patients, however, at least some tumor burden will remain during long-term follow-up. This study found that most of these patients reached a stable disease status without further surgeries. Multidisciplinary team decisions must balance the goal of complete resection, risk factors, repeated surgeries, and possible treatment alternatives in a wide range of heterogeneous entities. Procedural details and neurological outcome should be recorded to better assess their impact on long-term outcome.