Long-term outcome of surgically treated and conservatively managed Rathke cleft cysts.

OBJECTIVE: Rathke cleft cysts (RCC) are benign lesions of the sellar region that require surgical treatment in case of visual deterioration or progression of the cyst. However, the natural course is often stable and asymptomatic. We aimed to investigate the characteristics of patients with cyst progression during follow-up (FU) and to compare the natural history of patients with RCC with patients who underwent surgery. METHODS: Patients with an MR morphologic cystic sellar lesion classified as RCC between 04/2001 and 11/2020 were included. Functional outcomes, including ophthalmologic, endocrinologic, and MRI data, were retrospectively analyzed and compared between surgically treated patients, patients on a "watch and wait" strategy (WWS), and patients on a WWS who underwent secondary surgery due to cyst progression. RESULTS: One hundred forty patients (median age 42.8 years) with RCC on MRI were identified. 52/140 (37.1%) underwent primary surgery. Of 88 patients (62.9%) with initial WWS, 21 (23.9%) underwent surgery for secondary cyst progression. Patients on the WWS had significantly smaller cyst volumes (p = 0.0001) and fewer visual disturbances (p = 0.0004), but a similar rate of hormone deficiencies (p = 0.99) compared with surgically treated patients preoperatively. Postoperatively patients suffered significantly more often from hormone deficiencies than WWS patients (p = 0.001). Patients who switched to the surgical group were significantly more likely to have preoperative T1 hyperintense signals on MRI (p = 0.0001) and visual disturbances (p = 0.001) than patients with continuous WWS. Postoperatively, these patients suffered more frequently from new hormonal deficiencies (p = 0.001). Endocrine and ophthalmologic outcomes in patients with primary and secondary surgery were comparable. Multivariate analysis showed that WWS patients were at a higher risk of requiring surgery for cyst progression when perimetric deficits (p = 0.006), hyperprolactinemia (p = 0.003), and corticotropic deficits (p = 0.005) were present. CONCLUSION: Surgical treatment of RCC may cause new hormonal deficiencies, which are rare in the natural course. Therefore, the indication for surgery should be carefully evaluated. Hyperprolactinemia and corticotropic deficits were significant indicators for a secondary cyst progression in patients with RCC. However, a significant amount of almost 25% of initially conservatively managed cysts showed deterioration, necessary for surgical intervention.

A prospective randomized comparison of functional and cosmetic outcomes of a coronal zigzag incision versus a conventional straight incision pattern for craniotomy.

OBJECTIVE: Wound healing problems after neurosurgical procedures can lead to serious complications and may require complex revision or even reconstructive surgery. Therefore, optimal surgical management is critical to prevent complications. In a recent experimental study in animals, the authors demonstrated the superiority of a zigzag skin incision over a straight incision pattern. In this study, the authors applied these findings to clinical situations of neurosurgical patients with an indication for a coronal skin incision. The aim of this study was to objectively assess the functional and cosmetic outcomes between straight coronal and zigzag incisions in neurosurgical procedures. METHODS: This prospective, randomized, controlled, single-center trial included adult patients undergoing frontal craniotomy for cerebrovascular or tumor pathologies. The study primarily included patients who were not expected to receive adjuvant radiation or chemotherapy. The zigzag incision was standardized using a template. A common straight skin incision behind the hairline served as a control. Complication rates, functional (2-point discrimination, width of the wound, Vancouver Scar Scale [VSS], and Patient and Observer Scar Assessment Scale [POSAS]), and cosmetic outcomes were assessed postoperatively and at 3-month follow-up evaluations. Additionally, all patients answered a wound-specific questionnaire and the SF-36 questionnaire. RESULTS: Twenty-eight patients were randomized to the zigzag and 29 to the straight incision groups. Indications for surgery were cerebrovascular in 16 cases and tumors in 41 cases. Risk factors for wound healing were equally distributed in both groups. One patient in the zigzag group with poor postoperative compliance required surgery for secondary wound healing problems. Overall, the width of the scar was significantly smaller (p = 0.001) and local 2-point discrimination better (p = 0.005) in the zigzag group. Scores on the VSS (p = 0.003) and POSAS (p = 0.005) proved to be significantly superior in the zigzag group as well. CONCLUSIONS: A zigzag coronal skin incision pattern leads to significantly superior functional and cosmetic outcome scores. For certain patient groups, these findings may prove to be practice-changing.

Prevalence and clinical correlations of SF3B1 variants in lactotroph tumours.

OBJECTIVE: A somatic mutational hotspot in the SF3B1 gene was reported in lactotroph tumours. The aim of our study was to examine the prevalence of driver SF3B1 variants in a multicentre independent cohort of patients with lactotroph tumours and correlate with clinical data. DESIGN AND METHODS: This was a retrospective, multicentre study involving 282 patients with lactotroph tumours (including 6 metastatic lactotroph tumours) from 8 European centres. We screened SF3B1 exon 14 hotspot for somatic variants using Sanger sequencing and correlated with clinicopathological data. RESULTS: We detected SF3B1 variants in seven patients with lactotroph tumours: c.1874G > A (p.Arg625His) (n = 4, 3 of which metastatic) and a previously undescribed in pituitary tumours variant c.1873C > T (p.Arg625Cys) (n = 3 aggressive pituitary tumours). In two metastatic lactotroph tumours with tissue available, the variant was detected in both primary tumour and metastasis. The overall prevalence of likely pathogenic SF3B1 variants in lactotroph tumours was 2.5%, but when we considered only metastatic cases, it reached the 50%. SF3B1 variants correlated with significantly larger tumour size; higher Ki67 proliferation index; multiple treatments, including radiotherapy and chemotherapy; increased disease-specific death; and shorter postoperative survival. CONCLUSIONS: SF3B1 variants are uncommon in lactotroph tumours but may be frequent in metastatic lactotroph tumours. When present, they associate with aggressive tumour behaviour and worse clinical outcome.

Nuclear translocation of beta catenin in patients with Rathke cleft cysts-clinical and imaging characteristics and risk of recurrence.

PURPOSE: Although Rathke cleft cysts (RCC) are benign lesions of the sellar region, recurrence is frequent after surgical treatment. Nuclear translocation of ß-catenin (NTßC), a key effector of the wnt-signaling pathway that is responsible for cell renewal, has been shown to act as a proto-oncogene and is considered to be a potential risk factor for increased recurrence in RCC. In this study, we analyzed a surgically treated cohort into patients with and without NTßC expression in order to identify clinical and imaging differences and further evaluate the risk of recurrence. METHODS: Patients with resection of RCC between 04/2001 and 11/2020 were included. Histological specimens were immunohistochemically stained for ß-catenin. Study endpoints were time to cyst recurrence (TTR) and functional outcome. Functional outcome included ophthalmological and endocrinological data. Furthermore, MRI data were assessed. RESULTS: Seventy-three patients (median age 42.3 years) with RCC underwent mainly transsphenoidal cyst resection (95.9%), 4.1% via transcranial approach. Immunohistochemical staining for ß-catenin was feasible in 61/73 (83.6%) patients, with nuclear translocation detected in 13/61 cases (21.3%). Patients with and without NTßC were equally likely to present with endocrine dysfunction before surgery (p = 0.49). Postoperative new hypopituitarism occurred in 14/73 (19.2%) patients. Preoperative visual impairment was equal in both groups (p = 0.52). Vision improved in 8/21 (33.3%) patients and visual field deficits in 22/34 (64.7%) after surgery. There was no difference in visual and perimetric outcome between patients with and without NTßC (p = 0.45 and p = 0.23, respectively). On preoperative MRI, cyst volume (9.9 vs. 8.2 cm3; p = 0.4) and evidence of hemorrhage (30.8% vs. 35.4%; p = 0.99) were equal and postoperative cyst volume decreased significantly in both groups (0.7 vs. 0.5 cm3; p < 0.0001 each). Cyst progression occurred in 13/73 (17.8%) patients after 39.3 ± 60.3 months. Cyst drainage with partial removal of the cyst wall resulted in improved recurrence-free survival without increasing the risk of complications compared with cyst fenestration alone. Patients with postoperative diabetes insipidus had an increased risk for recurrence according to multivariate analysis (p = 0.005). NTßC was evident in 4/15 patients (26.7%) and was not associated with a higher risk for recurrence (p = 0.67). CONCLUSION: Transnasal transsphenoidal cyst drainage with partial removal of the cyst wall reduces the risk of recurrence without increasing the risk of complications compared with fenestration of the cyst alone. Patients with postoperative diabetes insipidus seem to have an increased risk for recurrence. In contrast, NTßC was not associated with a higher risk of recurrence and did not provide stratification for clinically distinct patients.

Meningioma involving the superior sagittal sinus: long-term outcome after robotic radiosurgery in primary and recurrent situation.

Objective: Treatment for meningiomas involving the superior sagittal sinus (SSS) is challenging and proved to be associated with higher risks compared to other brain locations. Therapeutical strategies may be either microsurgical (sub-)total resection or adjuvant radiation, or a combination of both. Thrombosis or SSS occlusion following resection or radiosurgery needs to be further elucidated to assess whether single or combined treatment is superior. We here present tumor control and side effect data of robotic radiosurgery (RRS) in combination with or without microsurgery. Methods: From our prospective database, we identified 137 patients with WHO grade I meningioma involving the SSS consecutively treated between 2005 and 2020. Treatment decisions were interdisciplinary. Patients underwent RRS as initial/solitary treatment (group 1), as adjuvant treatment after subtotal resection (group 2), or due to recurrent tumor growth after preceding microsurgery (group 3). Positive tumor response was assessed by MRI and defined as reduction of more than 50% of volume. Study endpoints were time to recurrence (TTR), time to RRS, risk factors for decreased survival, and side effects. Overall and specific recurrence rates for treatment groups were analyzed. Side effect data included therapy-related morbidity during follow-up (FU). Results: A total of 137 patients (median age, 58.3 years) with SSS meningiomas WHO grade I were analyzed: 51 patients (37.2%) in group 1, 15 patients (11.0%) in group 2, and 71 patients (51.8%) in group 3. Positive MR (morphological response) to therapy was achieved in 50 patients (36.4%), no response was observed in 25 patients (18.2%), and radiological tumor progression was detected in 8 patients (5.8%). Overall 5-year probability of tumor recurrence was 15.8% (median TTR, 41.6 months). Five-year probabilities of recurrence were 0%, 8.3.%, and 21.5% for groups 1-3 (p = 0.06). In multivariate analysis, tumor volume was significantly associated with extent of SSS occlusion (p = 0.026) and sex (p = 0.011). Tumor volume significantly correlated with TTR (p = 0.0046). Acute sinus venous thrombosis or venous congestion-associated bleedings did not occur in any of the groups. Conclusion: RRS for grade I meningiomas with SSS involvement represents a good option as first-line treatment, occasionally also in recurrent and adjuvant scenarios as part of a multimodal treatment strategy.

Spinal Tuberculosis within the Vertebral Arch Mimicking a Malignant Tumor: Case Report.

BACKGROUND: Spinal tuberculosis is a manifestation of extrapulmonary tuberculosis. The incidence of tuberculosis is low in high-income countries; however, globally, it still remains one of the most frequent fatal infectious diseases. Because of its rarity in developed countries, spinal tuberculosis can be mistaken for malignant tumors of the spine, especially in case of an atypical radiologic manifestation and without pulmonary affection. METHODS: We present the case of a 39-year-old man from South India with quickly progressing gait disturbance and hypesthesia below the Th10 level. Magnetic resonance imaging revealed an osteolytic lesion of the vertebral arch Th2 with central necrosis and compression of the spinal cord altogether highly suspicious for spinal metastasis. RESULTS: After surgical removal of the mass by laminectomy, the patient regained normal neurologic function. Histology revealed a severe granulomatous inflammation and DNAhybridization of polymerase chain reaction (PCR) products detected Mycobacterium tuberculosis-specific DNA in the sample. Biopsy of an enlarged hilar lymphnode allowed us to obtain material to successfully perform a drug resistance test to start specific antimicrobial therapy. CONCLUSION: Spinal tuberculosis, even with atypical radiologic appearance, has to be considered a differential diagnosis in patients with provenance from endemic countries. A multidisciplinary diagnostic approach helps perform antimicrobial susceptibility testing to avoid delaying the start of antibiotic therapy.

A simple surgical technique for sellar closure after transsphenoidal resection of pituitary adenomas in the context of risk factors for cerebrospinal fluid leaks and meningitis.

OBJECTIVE: The transsphenoidal approach is the standard for most pituitary tumors. Despite low morbidity, postoperative CSF fistulas and meningitis are specific complications. Various surgical closure techniques for intraoperative CSF (iCSF) leak and sellar reconstruction have been described. For many years the authors have applied synthetic materials for iCSF leak repair and sellar closure in a standardized fashion in their department. Here they analyze the surgical outcome as well as risk factors for iCSF leak and meningitis. METHODS: All patients with transsphenoidal resection of a pituitary adenoma performed by the same surgeon between January 2013 and December 2019 were screened retrospectively. A small amount of iCSF flow without a diaphragmatic defect was classified as a minor leak, and obvious CSF flow with or without a diaphragmatic defect was classified as a major leak. In case of iCSF leak, a fibrin- and thrombin-coated sponge was used to cover the diaphragmatic defect and another one was used for the sellar opening. A gelatin sponge was placed in the sphenoid sinus as an abutment. The primary and secondary outcomes were the number of postoperative CSF (pCSF) leaks and meningitis, respectively. Clinical, histological, and perioperative data from medical records were collected to identify risk factors for CSF leak and meningitis. RESULTS: Of 417 transsphenoidal surgeries, 359 procedures in 348 patients with a median age of 54 years were included. There were 96 iCSF leaks (26.7%; 37.5% major, 62.5% minor). In 3 of 359 cases (0.8%) a pCSF fistula occurred, requiring revision surgery in 2 patients and a lumbar drain in 1 patient. Meningitis occurred in 3 of 359 cases (0.8%). All 3 patients recovered without sequelae after antibiotic therapy. According to univariate analysis, risk factors for iCSF leak were macroadenoma (p = 0.006) and recurrent adenoma (p = 0.032). An iCSF leak was found less often in functioning adenomas (p = 0.025). In multivariate analysis recurrent tumors remained as a risk factor (p = 0.021) for iCSF leak. Patients with iCSF leak were at increased risk for a pCSF leak (p = 0.005). A pCSF leak in turn represented the key risk factor for meningitis (p = 0.033). CONCLUSIONS: Patients with macroadenomas and recurrent adenomas are especially at risk for iCSF leak. An iCSF leak in turn increases the risk for a pCSF leak, which carries the risk for meningitis. The authors' surgical technique leads to a very low rate of pCSF leaks and meningitis without using autologous graft materials. Hence, this technique is safe and improves patient comfort by avoiding the disadvantages of autologous graft harvesting.

TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome.

Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing's disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.

Acute Hiccups Detected by Electromyographic Recordings During Resection of a Vestibular Schwannoma.

BACKGROUND AND IMPORTANCE: Intraoperative neuromonitoring (IONM) is routinely used to monitor cranial nerve function during resection of vestibular schwannomas. Sudden movements in the surgical field can be a disturbing factor for the surgeon. IONM can help determine the cause of unexpected patient movements. CLINICAL PRESENTATION: We report the case of a 54-year-old patient who underwent retromastoid craniotomy and resection of a vestibular schwannoma. Toward the end of dissection of the tumor from the lower cranial nerves and brainstem, the patient showed repetitive shoulder elevation. Electroencephalography showed burst suppression, confirming deep sedation and excluding voluntary movements. Free-running electromyography recorded spontaneous, simultaneous, bilateral vocal cord activity that was synchronous with upper body movement. There was simultaneous but smaller activity in the right genioglossus muscle and levator veli palatini, indicative for far-field activity. These IONM findings allowed us to classify the clinical observations as intraoperative hiccups. CONCLUSION: Hiccups during general anesthesia are rare but should be considered as a differential diagnosis of sudden upper body movement. To the best of our knowledge, this is the first reported case of acute hiccups during resection of a vestibular schwannoma. IONM reliably distinguished it from an increase in intraoperative consciousness or accessory nerve activation resulting in shoulder movements.

Improved pasireotide response in USP8 mutant corticotroph tumours in vitro.

Cushing's disease is a rare but devastating and difficult to manage condition. The somatostatin analogue pasireotide is the only pituitary-targeting pharmaceutical approved for the treatment of Cushing's disease but is accompanied by varying efficacy and potentially severe side effects. Finding means to predict which patients are more likely to benefit from this treatment may improve their management. More than half of corticotroph tumours harbour mutations in the USP8 gene, and there is evidence of higher somatostatin receptor 5 (SSTR5) expression in the USP8-mutant tumours. Pasireotide has a high affinity for SSTR5, indicating that these tumours may be more sensitive to treatment. To test this hypothesis, we examined the inhibitory action of pasireotide on adrenocorticotrophic hormone synthesis in primary cultures of human corticotroph tumour with assessed USP8 mutational status and in immortalized murine corticotroph tumour cells overexpressing human USP8 mutants frequent in Cushing's disease. Our in vitro results demonstrate that pasireotide exerts a higher antisecretory response in USP8-mutant corticotroph tumours. Overexpressing USP8 mutants in a murine corticotroph tumour cell model increased endogenous somatostatin receptor 5 (Sstr5) transcription. The murine Sstr5 promoter has two binding sites for the activating protein 1 (AP-1) and USP8 mutants possibly to mediate their action by stimulating AP-1 transcriptional activity. Our data corroborate the USP8 mutational status as a potential marker of pasireotide response and describe a potential mechanism through which USP8 mutants may regulate SSTR5 gene expression.

Headache characteristics and postoperative course in Chiari I malformation.

BACKGROUND: Chiari I malformation typically presents with cough headache. However, migraine-like or tension-type-like headaches may also occur. There are limited publications on Chiari I malformation-associated headache semiologies and the effect of foramen magnum decompression on different headache types. METHODS: A retrospective analysis complemented by structured phone interviews was performed on 65 patients with Chiari I malformation, treated at our hospital between 2010 and 2021. Headache semiology (according to ICHD-3), frequency, intensity, and radiological characteristics were evaluated pre- and postoperatively. RESULTS: We included 65 patients. 38 patients were female and 27 male. Mean age was 43.9 ± 15.7 years. Headache was predominant in 41 patients (63.0%). Twenty-one patients had cough headache and 20 had atypical headache (12 migrainous, eight tension-type headache-like). Thirty-five patients with headache underwent surgery. Frequency, intensity, and analgesic use was significantly reduced in cough headache (p < 0.001). Atypical headaches improved less (p = 0.004 to 0.176). Exploratory analysis suggested that larger preoperative tonsillar descent correlated with larger postoperative headache intensity relief (p = 0.025). CONCLUSION: Decompression was effective in Chiari I malformation-related cough headache. Atypical headache responded less well, and the causal relation with Chiari I malformation remains uncertain. For atypical headache, decompression should only be considered after failed appropriate preventive therapy and within an interdisciplinary approach involving a neurologist.

Detection of impending perfusion deficits by intraoperative computed tomography (iCT) in aneurysm surgery of the anterior circulation.

BACKGROUND: The aim of our study was to evaluate the additional benefit of intraoperative computed tomography (iCT), intraoperative computed tomography angiography (iCTA), and intraoperative computed tomography perfusion (iCTP) in the intraoperative detection of impending ischemia to established methods (indocyanine green videoangiography (ICGVA), microDoppler, intraoperative neuromonitoring (IONM)) for initiating timely therapeutic measures. METHODS: Patients with primary aneurysms of the anterior circulation between October 2016 and December 2019 were included. Data of iCT modalities compared to other techniques (ICGVA, microDoppler, IONM) was recorded with emphasis on resulting operative conclusions leading to inspection of clip position, repositioning, or immediate initiation of conservative treatment strategies. Additional variables analyzed included patient demographics, aneurysm-specific characteristics, and clinical outcome. RESULTS: Of 194 consecutive patients, 93 patients with 100 aneurysms received iCT imaging. While IONM and ICGVA were normal, an altered vessel patency in iCTA was detected in 5 (5.4%) and a mismatch in iCTP in 7 patients (7.5%). Repositioning was considered appropriate in 2 patients (2.2%), where immediate improvement in iCTP could be documented. In a further 5 cases (5.4%), intensified conservative therapy was immediately initiated treating the reduced CBP as clip repositioning was not considered causal. In terms of clinical outcome at last FU, mRS0 was achieved in 85 (91.4%) and mRS1-2 in 7 (7.5%) and remained mRS4 in one patient with SAH (1.1%). CONCLUSIONS: Especially iCTP can reveal signs of impending ischemia in selected cases and enable the surgeon to promptly initiate therapeutic measures such as clip repositioning or intraoperative onset of maximum conservative treatment, while established tools might fail to detect those intraoperative pathologic changes.

Multimodal therapy of cavernous sinus meningioma: Impact of surgery and 68Ga-DOTATATE PET-guided radiation therapy on tumor control and functional outcome.

BACKGROUND: Functional preservation in patients with WHO grade I meningioma involving the cavernous sinus (CSM) is crucial for long-term tumor control. Concise data on the functional outcome of an interdisciplinary, multimodal treatment are scarce. We analyzed functional outcome and tumor control in CSM patients following maximal safe resection (MSR), fractionated stereotactic radiotherapy (FSRT), or combination of them, retrospectively. METHODS: Patients with WHO grade I CSM treated between 2003 and 2017 were included. Prior to FSRT, a 68Ga-DOTATATE PET/CT was performed for radiation planning. Progression-free survival (PFS) was analyzed using Kaplan-Meier method and log-rank test was performed to test differences between groups. Visual function was analyzed at baseline and follow-up. RESULTS: Eighty-five patients were included. MSR alone was performed in 48 patients (group A), MSR followed by FSRT in 25 patients (group B), and FSRT alone in 12 patients (group C). Intracranial tumor volumes were higher in A and B compared to C (median 9.2/10.8/4.3 ccm for A/B/C, P = .023). Median follow-up was 47/46/45 months and PFS at 5 years 55.7%, 100%, and 100% in A/B/C, respectively (P < .001). Optic nerve compression was more common in A (91.7%) and B (84.0%) than C (16.7%), P < .001. Post-therapeutic new onset or deterioration of double vision was observed in 29% (A), 17% (B), and 0% (C). CONCLUSION: Personalized treatment strategies for CSM are essential to control space-occupying or functionally compromising lesions. The additional potential side effect of radiotherapy seems to be justified under the aspect of longer tumor control with low functional risk. Without space-occupying effect of CSM, FSRT alone is reasonably possible.

Lamina cribrosa perforation during nasotracheal intubation in neonates: case series and review of the literature.

Intracranial penetration during attempted nasotracheal intubation is a potentially devastating complication, which should be carefully evaluated and the risk should be addressed in neonatal resuscitation trainings.

Past medical history of tumors other than meningioma is a negative prognostic factor for tumor recurrence in meningiomas WHO grade I.

BACKGROUND: Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. METHODS: We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients' past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. RESULTS: Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21-89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431-6.771) both on uni- and multivariate analysis. CONCLUSION: Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence.

Takotsubo cardiomyopathy in a 12-year-old boy caused by acute brainstem bleeding-a case report.

Takotsubo cardiomyopathy is characterized by acute and reversible severe left ventricular dysfunction due to intensive emotional or physical stress followed by catecholamine excess. Traditionally it is most common in postmenopausal women, whereas only few cases have been described in childhood. In our case a previously well 12-year-old boy presented with severe cardiogenic shock due to dramatically impaired left ventricular function requiring significant inotropic support and invasive mechanical ventilation. Interestingly, cardiac catheterization, myocardial tissue histology and biochemical laboratory tests did not yield a definitive diagnosis. As his cardiac function improved gradually within several days and deep sedation could be weaned, he was then found to suffer from hemiparesis and absence of protective airway reflexes on neurological examination during the weaning process. Subsequent brain imaging studies revealed a brainstem bleeding due to a fistulous arteriovenous malformation (AVM) appearing to be only a few days old. After endovascular coiling and subsequent microsurgical resection of the malformation, he recovered completely. Our present case demonstrated, that brainstem bleeding could precipitate Takotsubo cardiomyopathy manifesting hemodynamic collapse. Severe ventricular impairment has been described in many adults with subarachnoid hemorrhage; however, this condition is extremely rare among children. When severe cardiogenic shock is diagnosed, precipitating factors such as intracranial processes should be ruled out on a regular basis.

Simpson Grade Revisited - Intraoperative Estimation of the Extent of Resection in Meningiomas Versus Postoperative Somatostatin Receptor Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging.

BACKGROUND: Surgeon's intraoperative estimation of meningioma extent of resection (Simpson Grade, SG) is widely used as a prognostic factor for recurrence. However, the validity of SG is still a matter of debate. In preoperative imaging, 68Ga-DOTATATE/PET-CT has been shown to detect meningioma tissue even more sensitively than magnetic resonance imaging (MRI). OBJECTIVE: To evaluate the Simpson grading within the framework of modern postoperative imaging techniques (MRI; PET-CT). METHODS: At first, patients with WHO grade I meningioma, surgical resection, and postoperative 68Ga-DOTATATE/PET-CT within 6 mo after surgery were retrospectively analyzed. Second, an analogous prospective cohort of patients with WHO grade I meningioma was investigated by comparing SG after meningioma removal with postoperative MRI and 68Ga-DOTATATE/PET-CT within 6 mo after surgery. RESULTS: A total of 37 patients were retrospectively analyzed. In total, 5/8 patients with SG-I and II resections showed tumor remnants according to postoperative PET-CT (SG 62.5% false negative). In the prospective cohort of 52 tumors, PET-CT displayed tracer uptake in 15/37 SG-I or II resections indicating unexpected tumor remnants (SG 40.5% false negative). MRI was false negative in 7 of these 15 cases (MRI 18.9% false negative) (P = .037). Discordant results according to PET-CT were more often found in convexity (40%) and falcine (46.7%) meningiomas than in skull base meningiomas (18.2%). CONCLUSION: Intraoperative Simpson grading is at risk to underestimate tumor remnants, predominantly in grade I and II resections. Postoperative PET-CT improves detection rates compared to MRI. Prognostic impact of postoperative meningioma remnants according to PET-CT needs to be investigated prospectively.

Magnetic Resonance Imaging-Based Robotic Radiosurgery of Arteriovenous Malformations.

OBJECTIVE: CyberKnife offers CT- and MRI-based treatment planning without the need for stereotactically acquired DSA. The literature on CyberKnife treatment of cerebral AVMs is sparse. Here, a large series focusing on cerebral AVMs treated by the frameless CyberKnife stereotactic radiosurgery (SRS) system was analyzed. METHODS: In this retrospective study, patients with cerebral AVMs treated by CyberKnife SRS between 2005 and 2019 were included. Planning was MRI- and CT-based. Conventional DSA was not coregistered to the MRI and CT scans used for treatment planning and was only used as an adjunct. Obliteration dynamics and clinical outcome were analyzed. RESULTS: 215 patients were included. 53.0% received SRS as first treatment; the rest underwent previous surgery, embolization, SRS, or a combination. Most AVMs were classified as Spetzler-Martin grade I to III (54.9%). Hemorrhage before treatment occurred in 46.0%. Patients suffered from headache (28.8%), and seizures (14.0%) in the majority of cases. The median SRS dose was 18 Gy and the median target volume was 2.4 cm³. New neurological deficits occurred in 5.1% after SRS, with all but one patient recovering. The yearly post-SRS hemorrhage incidence was 1.3%. In 152 patients who were followed-up for at least three years, 47.4% showed complete AVM obliteration within this period. Cox regression analysis revealed Spetzler-Martin grade (P = 0.006) to be the only independent predictor of complete obliteration. CONCLUSIONS: Although data on radiotherapy of AVMs is available, this is one of the largest series, focusing exclusively on CyberKnife treatment. Safety and efficacy compared favorably to frame-based systems. Non-invasive treatment planning, with a frameless SRS robotic system might provide higher patient comfort, a less invasive treatment option, and lower radiation exposure.

Perioperative Management of a Patient with Severe Factor V Deficiency Presenting with Chronic Subdural Hematoma: A Clinical Report.

BACKGROUND: Severe factor V deficiency is an extremely rare coagulation disorder. Patients with factor V activity <5% usually become symptomatic in early childhood. CASE DESCRIPTION: We report the case of an 82-year-old woman with incidentally diagnosed severe factor V deficiency, who developed a symptomatic chronic subdural hematoma, requiring burr hole craniostomy. Successful management was achieved by a multidisciplinary approach. Preoperatively, factor V activity was increased from 2% to 50% by administration of 25 mL/kg body weight of fresh frozen plasma over 30 minutes under close cardiopulmonary monitoring in the intensive care unit. Straight afterward, the patient was transferred to the operating room where surgery was performed under general anesthesia. Burr hole craniostomy could be performed without perioperative complications. In the postoperative days, there was no relevant recurrence of the subdural hematoma in the follow-up computed tomography scans under frequent control of coagulation parameters. However, despite further transfusion of fresh frozen plasma, factor V activity did not increase >16%. The patient was discharged without any neurologic deficits. In a hemostaseologic follow-up 2 months after surgery, factor V activity <1% was confirmed with evidence of a factor V inhibitor in the modified Bethesda assay. Most likely, the patient suffered from an acquired form of factor V deficiency with preformed antibodies that had been boosted by the initial treatment with fresh frozen plasma. CONCLUSIONS: We conclude that in this rare bleeding disorder, intracranial surgery was successfully managed because of a thoroughly planned perioperative therapeutic strategy. However, if there is time prior to surgery, a full checkup of the bleeding disorder is advisable.