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Here, we describe two congenitally deaf male siblings with the same compound heterozygotic, likely pathogenic mutations in the FGF3 gene, associated with the labyrinthine aplasia, microtia and microdontia (LAMM) syndrome. Both children had bilateral cochleovestibular aplasia, precluding cochlear implantation. The elder brother received an auditory brainstem implant (ABI) with very limited auditory responses. During the ABI-surgery of the younger subject, it was discovered that excellent auditory responses could be obtained when the electrode array was placed considerably more caudally and more medially than standard. It was observed that the foramen of Luschka, the entrance to the lateral recess of the fourth ventricle was located more caudally. In view of this observation the good auditory development of the latter child, it was decided to give the older child a contralateral ABI. Again, it turned out that the anatomy of the brainstem was abnormal with a more caudal location of the foramen of Luschka and the cochlear nucleus, and this child is showing good progress with his auditory development. It is concluded that one should be aware of the anatomical differences at the level of the brainstem when placing an ABI in children with this genetic disorder (and most likely also in the LAMM syndrome). This also underpins the need of a multidisciplinary approach with closely collaborating team members and good family guidance when diagnosing and treating children with rare deafness., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background and Objectives: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH., Methods: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade ( p = 0.10)., Results: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56)., Discussion: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care., Trial Registration Information: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013)., Classification of Evidence: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Objective: This study evaluates the natural course of hearing loss (HL) prior to treatment in patients with progressive tumors and an indication for active intervention. Evaluating this patient group specifically can put hearing outcomes after vestibular schwannoma therapy into an adequate context., Study Design: Retrospective cohort study., Setting: Tertiary referral center., Methods: Inclusion criteria comprised unilateral vestibular schwannomas prior to active treatment, with ≥2 mm extracanalicular (EC) tumor growth and ≥2 audiograms. We performed a comprehensive assessment of hearing using multiple outcome parameters including (the annual decrease in) pure-tone averages (PTAs; an average of 0.5, 1, 2, and 3 kHz). Predictors for HL were evaluated (patient age, tumor size/progression, follow-up duration, baseline hearing)., Results: At presentation, 86% of patients suffered from sensorineural HL on the affected side (≥20 dB PTA) with a median of 39 dB (interquartile rate [IQR]: 27-51 dB). The median follow-up duration was 21 months (IQR: 13-34 months), after which 58% (187/322) of patients experienced progressive HL (≥10 dB), with a median increase of 6.4 dB/year. At the last follow-up, the median PTA was 56 dB (IQR: 37-73). Median speech discrimination scores deteriorated from 90% (IQR: 70%-100%) to 65% (IQR: 35%-100%). Tumor progression (maximal EC diameter) was significantly correlated to the progression of sensorineural HL, corrected for follow-up (F(2,228) = 10.4, p < .001, R 2  = 8%)., Conclusion: The majority of patients (58%) with radiologically confirmed progressive vestibular schwannomas experience progressive sensorineural HL during observation. Tumor progression rate, EC tumor extension, and longer follow-up are factors associated with more sensorineural HL., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objective  The aim of this study was to assess the ability to smile following a hypoglossal-facial nerve transfer (N12-N7). Design  This is a retrospective chart review. Setting  National tertiary referral center for skull base pathology. Participants  Seventeen patients. Main Outcome Measures  The ability to smile following an N12-N7 transfer was assessed by five medical doctors on photographs of the whole face and frontal, orbital, and oral segments. The (segmented) photographs were scored for the symmetry, asymmetry, and correct or incorrect assessment of the affected side. Results  Seventeen patients were analyzed by 5 assessors providing 85 assessments. The whole face at rest was judged symmetrical in 26% of the cases and mildly asymmetrical in 56%. Frontal, orbital, and oral segments were symmetrical in 63, 20, and 35%, respectively. The affected side was correctly identified in 76%. When smiling, the whole face was symmetrical in 6% and mildly asymmetric in 59%. The affected side was correctly identified in 94%. The frontal, orbital, and oral segments during smiling were symmetrical in 67, 15, and 6%, respectively. The affected side of the frontal, orbital, and buccal facial segments during smiling was correctly identified in 89, 89, and 96%, respectively. Interobserver variability with Fleiss' kappa analysis showed that the strength of the agreement during smile of the total face was good (0.771) Conclusion  Following an N12-N7 transfer, a good facial symmetry at rest can be achieved. During smiling, almost all patients showed asymmetry of the face, which was predominantly determined by the orbital and oral segments. To improve the ability to smile after an N12-N7 transfer, additional procedures are needed., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Objective: Vestibular schwannoma management aims to maintain optimal quality of life (QoL) while preventing severe sequelae of the tumor or its treatment. This study assessed long-term QoL of patients with vestibular schwannoma in relation to treatment modality and decisional regret., Study Design: A longitudinal study, in which clinical and QoL data were used that were cross-sectionally acquired in 2014 and again in 2020 from the same patient group., Setting: A tertiary expert center for vestibular schwannoma care in the Netherlands., Methods: QoL was measured by the Penn Acoustic Quality of Life (PANQOL) scale. Changes in time were assed using a linear mixed model. In addition, the Decision Regret Scale was analyzed., Results: Of 867 patients, 536 responded (62%), with a median follow-up of 11 years. All PANQOL subdomain scores remained stable over time and did not exceed minimal clinically important difference (MCID) levels. Time since treatment did not affect QoL. Patients had comparable average QoL scores and proportions of patients with changing QoL scores (ie, exceeding the MCID) over time, irrespective of the received initial treatment. Female patients and those who required salvage therapy (either by radiotherapy or surgery) reported a lower QoL. The latter patient group reported the highest decisional regret., Conclusion: On average, the long-term QoL of patients with vestibular schwannoma is comparable for patients under active surveillance and those who have received active treatment, and it remains stable over time. This suggests that, on average, preservation of QoL of patients with vestibular schwannoma is feasible when adequately managed., (© 2022 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objective: To analyze the effect of dizziness-related symptoms on the long-term quality of life (QoL) of patients with unilateral vestibular schwannoma., Methods: In this cross-sectional study, patients with a unilateral vestibular schwannoma diagnosed between 2004 and 2013 completed a disease-specific QoL questionnaire (Penn Acoustic Neuroma Quality of Life [PANQOL]) and the Dizziness Handicap Inventory (DHI) in 2020. Linear regression was performed to assess the correlation between QoL and the DHI total score, and the scores of the DHI functional, emotional, and physical subdomains. Potential confounders such as age, sex, tumor size at baseline, and treatment modality (active surveillance, surgery, or radiotherapy) were included in the model., Results: In total, 287 of 479 patients (59%) experienced dizziness with a median follow-up of 10 years. The DHI total score was significantly associated with the PANQOL total score. On average, we found a reduction of 0.7 points on the PANQOL for each additional point on the DHI. The DHI emotional subdomain was the most prominent determinant of poorer QoL. Each point on the DHI emotional subscale was associated with a reduction of 1.3 on the PANQOL score. Treatment modality did not have a clinically relevant effect on dizziness-related QoL., Conclusions: Even mild dizziness can have a significant and clinically relevant effect on the QoL of patients with unilateral vestibular schwannoma in the long term. This holds true for all treatment modalities. Addressing the vestibular problems may improve QoL in vestibular schwannoma patients, and DHI subscale analysis may help tailor the optimal vestibular intervention., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Background and Objectives: The ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected proportion of the included patients experienced nonaneurysmal subarachnoid hemorrhage. In this post hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at 6 months., Methods: The ULTRA trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013, and January 20, 2020. After confirmation of subarachnoid hemorrhage on noncontrast CT, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care or usual care only. In this post hoc analysis, we included all ULTRA participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin scale (mRS), dichotomized into good (0-3) and poor (4-6) outcomes., Results: Of the 813 ULTRA trial patients who experienced an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio [aOR] 0.92; 95% CI 0.69-1.24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) (aOR 0.76; 95% CI 0.57-1.03), all-cause mortality at 30 days (aOR 0.91; 95% CI 0.65-1.28), and all-cause mortality at 6 months (aOR 1.10; 95% CI 0.80-1.52)., Discussion: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcomes at 6 months in patients with aneurysmal subarachnoid hemorrhage and therefore cannot be recommended., Trial Registration Information: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013)., Classification of Evidence: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage., (© 2022 American Academy of Neurology.)

Purpose: The aim of this study is to compute and validate a statistical predictive model for the risk of recurrence, defined as regrowth of tumor necessitating salvage treatment, after translabyrinthine removal of vestibular schwannomas to individualize postoperative surveillance., Methods: The multivariable predictive model for risk of recurrence was based on retrospectively collected patient data between 1995 and 2017 at a tertiary referral center. To assess for internal validity of the prediction model tenfold cross-validation was performed. A 'low' calculated risk of recurrence in this study was set at < 1%, based on clinical criteria and expert opinion., Results: A total of 596 patients with 33 recurrences (5.5%) were included for analysis. The final prediction model consisted of the predictors 'age at time of surgery', 'preoperative tumor growth' and 'first postoperative MRI outcome'. The area under the receiver operating curve of the prediction model was 89%, with a C-index of 0.686 (95% CI 0.614-0.796) after cross-validation. The predicted probability for risk of recurrence was low (< 1%) in 373 patients (63%). The earliest recurrence in these low-risk patients was detected at 46 months after surgery., Conclusion: This study presents a well-performing prediction model for the risk of recurrence after translabyrinthine surgery for vestibular schwannoma. The prediction model can be used to tailor the postoperative surveillance to the estimated risk of recurrence of individual patients. It seems that especially in patients with an estimated low risk of recurrence, the interval between the first and second postoperative MRI can be safely prolonged., (© 2022. The Author(s).)

Background: Employment is an important factor in quality of life. For vestibular schwannoma (VS) patients, employment is not self-evident, because of the sequelae of the disease or its treatment and their effects on daily life., Objectives: This study assessed employment status, sick leave (absenteeism) and being less productive at work (presenteeism) in the long-term follow-up of VS patients, and evaluated the impact of treatment strategy (active surveillance, surgery or radiotherapy)., Methods: A cross-sectional survey study was performed in a tertiary university hospital in the Netherlands. Patients completed the iMTA-post productivity questionnaire (iPCQ). Employment status was compared to that of the general Dutch population. Employment, absenteeism and presenteeism were compared between patients under active surveillance, patients after radiotherapy and post-surgical patients., Result: In total 239 patients participated, of which 67% were employed at the time of the study. Only 14% had a disability pension, which was comparable to the age-matched general Dutch population. The proportion of patients with absenteeism was 8%, resulting in a 4% reduction of working hours. Presenteeism was reported by 14% of patients, resulting in a 2% reduction of working hours. The median number of working hours per week was 36, and since the diagnosis, these hours had been reduced by 6%. There were no significant differences between treatment modalities., Conclusion: On average, long-term employment status and working hours of VS patients are comparable to the age-matched general population. Treatment strategies do not seem to differentially impact on long-term employment of VS patients., (© 2021. The Author(s).)

Objective: To identify predictors of tumor recurrence and postoperative facial nerve function after translabyrinthine surgery for unilateral vestibular schwannomas., Study Design: Retrospective study., Setting: Tertiary referral center., Patients: Between 1996 and 2017 a total of 596 patients with unilateral vestibular schwannoma underwent translabyrinthine surgery. Pre- and postoperative clinical status, radiological, and surgical findings were evaluated., Interventions: Translabyrinthine surgery., Main Outcome Measures: Potential predictors for tumor recurrence and facial nerve outcome were analyzed using Cox regression and ordinal logistic regression, respectively., Results: The extent of tumor removal was total in 32%, near-total in 58%, and subtotal in 10%. In 5.5% (33/596) of patients the tumor recurred. Subtotal tumor resection (p = 0.004, hazard ratios [HR] = 10.66), a young age (p = 0.008, HR = 0.96), and tumor progression preoperatively (p = 0.042, HR = 2.32) significantly increased the risk of recurrence, whereas tumor size or histologic composition did not. A good postoperative facial nerve function (House-Brackmann grade 1-2) was achieved in 85%. The risk of postoperative facial nerve paresis or paralysis increased with tumor size (p < 0.001, OR = 1.52), but was not associated with the extent of tumor removal, histologic composition, or patient demographics., Conclusions: Translabyrinthine surgery is an effective treatment for vestibular schwannoma, with a good local control rate and facial nerve outcome. The extent of tumor removal is a clinically relevant predictor for tumor recurrence, as are young patient age and preoperative tumor progression. A large preoperative tumor size is associated with a higher risk of postoperative facial nerve paresis or paralysis., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Background: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months., Methods: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812., Findings: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups., Interpretation: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale., Funding: Fonds NutsOhra., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An Auditory Brainstem Implant (ABI) is a technique developed for patients with severe hearing loss. The ABI consists of a microphone and speech processor located on the scalp, which is connected to a transmitting and receiving coil and electrode on the brain stem placed in the skull. Eligible for an ABI are adults with cochlea and acoustic nerve damage due to neurofibromatosis type 2, and children with congenital malformation or aplasia, cochlear trauma or cochlear ossification after meningitis. An ABI can provide useful hearing. It has proven to be a safe procedure without serious complications. The entire ABI process is handled by a multidisciplinary team with extensive experience in cerebellopontine angle tumour surgery and cochlear implantation in adults and children. Concentration of this care in a specialized centre is important to maximize the chances of a successful outcome.

Background:  Both compression stockings and low molecular weight heparin (LMWH) are used for the prevention of post-operative venous thromboembolism (VTE) in cerebellopontine angle (CPA) tumour excisions., Objective:  In an attempt to optimise the prophylactic treatment in these patients, we compared LMWH (nadroparin) plus compression stockings to nadroparin as single therapy., Methods:  Patients undergoing CPA tumour excision in the period between January 2014 and November 2015 received nadroparin as a single therapy. Patients treated since November 2015 received, in addition to this therapy, peri-operative compression stockings as VTE prophylaxis due to a change in protocol. VTE was defined as symptomatic deep vein thrombosis or pulmonary embolism and was confirmed via radiological imaging or autopsy., Results:  A total of 146 consecutive patients were reviewed. Treatment groups were comparable with respect to demographics and risk factors. Six of the 60 patients (10.0%; 95% confidence interval [CI] 3.8-20.5) receiving nadroparin single therapy developed symptomatic VTE. One out of 86 patients (1.2%; 95% CI 0-6.3) treated with combination therapy developed VTE ( p  = 0.019) with a risk difference of 8.8% (95% CI 1.43-19.0). In comparison to combination therapy, nadroparin single therapy showed a relative risk of 8.6 (95% CI 1.1-69.6)., Conclusion:  Adding compression stockings to peri-operative nadroparin, as a prophylactic strategy for thromboembolic complications in patients undergoing surgical intervention for CPA tumours, was associated with a significant reduction in the occurrence of VTE., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: To evaluate long-term language development in children with prelingual deafness who received auditory brainstem implants (ABIs) compared with children who received cochlear implants (CIs) at the same hospital. Additional non-auditory disabilities were taken into account., Study Design: Retrospective cohort study., Setting: Tertiary referral center., Patients: Ten children with bilateral malformations of the cochlea and/or cochlear nerve who received ABIs, including seven with additional disabilities, and 147 children with CIs as a reference group, including 22 children with additional disabilities., Intervention: ABIs were implanted at 1.3 to 6.2 years of age. Follow-up ranged from 1.1 to 7.7 years., Main Outcome Measures: Receptive and expressive language abilities were assessed using the Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS), the Categories of Auditory Performance (CAP), the Meaningful Use of Speech Scale (MUSS), and the Speech Intelligibility Rate (SIR)., Results: Of the 10 children with ABIs, seven had long-term follow-up data. Within 1 year, six of the seven children with ABIs could identify sounds, respond to speech, and use their voice to attract attention. Language skills developed at a slower rate than in children with CIs and reached the same competence level when additional disabilities were absent. These language skills matched, on average, those of children with CIs with additional disabilities., Conclusion: For deaf children with bilateral inner ear malformations, ABIs provide satisfactory auditory input. Children with ABIs are able to develop receptive and expressive language skills comparable to those of children with CIs with additional disabilities. Using this knowledge, preoperative parent counselling can be refined.

Background: Surgical treatment of intracranial saccular aneurysms aims to prevent (re)hemorrhage by complete occlusion of the aneurysmal lumen. It is unclear whether routine postoperative imaging, to assess aneurysmal occlusion, is necessary since intraoperative assessment by the neurosurgeon may be sufficient. We assessed routine clinical protocols for post-clipping imaging in the Netherlands and determined whether intraoperative assessment of aneurysm clippings sufficiently predicts aneurysm residuals., Methods: A survey was conducted to assess postoperative imaging protocols in centers performing clipping of intracranial aneurysms in the Netherlands (n = 9). Furthermore, a retrospective single-center cohort study was performed to determine the predictive value of intraoperative assessment of aneurysm occlusion in relation to postoperative digital subtraction angiography (DSA) findings, between 2009 and 2017., Results: No center performed intraoperative DSA in a hybrid OR, routinely. Respectively, four (44.4%), seven (77.8%), and three (33.3%) centers did not routinely perform early postoperative imaging, late follow-up imaging, or any routine imaging at all. Regarding our retrospective study, 106 patients with 132 clipped aneurysms were included. There were 23 residuals ≥ 1 mm (17.4%), of which 10 (43.5%) were unexpected. For the presence of these residuals, intraoperative assessment showed a sensitivity of 56.5%, a specificity of 86.2%, a positive predictive value of 46.4%, and a negative predictive value of 90.4%., Conclusions: There is lack of consensus regarding the post-clipping imaging strategy in the Netherlands. Since intraoperative assessment is shown to be insufficient to predict postoperative aneurysm residuals, we advocate routine postoperative imaging after aneurysm clipping unless this is not warranted on the basis of patient age, clinical condition, and/or comorbidity.

Background: Chronic subdural haematoma (CSDH) is a common neurological disease with a rapidly rising incidence due to increasing age and widespread use of anticoagulants. Surgical intervention by burr-hole craniotomy (BHC) is the current standard practice for symptomatic patients, but associated with complications, a recurrence rate of up to 30% and increased mortality. Dexamethasone (DXM) therapy is, therefore, used as a non-surgical alternative but considered to achieve a lower success rate. Furthermore, the benefit of DXM therapy appears much more deliberate than the immediate relief from BHC. Lack of evidence and clinical equipoise among caregivers prompts the need for a head-to-head randomised controlled trial. The objective of this study is to compare the effect of primary DXM therapy versus primary BHC on functional outcome and cost-effectiveness in symptomatic patients with CSDH., Methods/design: This study is a prospective, multicentre, randomised controlled trial (RCT). Consecutive patients with a CSDH with a Markwalder Grading Scale (MGS) grade 1 to 3 will be randomised to treatment with DXM or BHC. The DXM treatment scheme will be 16 mg DXM per day (8 mg twice daily, days 1 to 4) which is then halved every 3 days until a dosage of 0.5 mg a day on day 19 and stopped on day 20. If the treatment response is insufficient (i.e. persistent or progressive symptomatology due to insufficient haematoma resolution), additional surgery can be performed. The primary outcomes are the functional outcome by means of the modified Rankin Scale (mRS) score at 3 months and cost-effectiveness at 12 months. Secondary outcomes are quality of life at 3 and 12 months using the Short Form Health Survey (SF-36) and Quality of Life after Brain Injury Overall Scale (QOLIBRI), haematoma thickness after 2 weeks on follow-up computed tomography (CT), haematoma recurrence during the first 12 months, complications and drug-related adverse events, failure of therapy within 12 months after randomisation and requiring intervention, mortality during the first 3 and 12 months, duration of hospital stay and overall healthcare and productivity costs. To test non-inferiority of DXM therapy compared to BHC, 210 patients in each treatment arm are required (assumed adjusted common odds ratio DXM compared to BHC 1.15, limit for inferiority < 0.9). The aim is to include a total of 420 patients in 3 years with an enrolment rate of 60%., Discussion: The present study should demonstrate whether treatment with DXM is as effective as BHC on functional outcome, at lower costs., Trial Registration: EUCTR 2015-001563-39 . Date of registration: 29 March 2015.

A 28-year-old man with genetically confirmed hyperostosis corticalis generalisata (Van Buchem disease) suffered from headache and progressive cognitive and sensibility disorders. Bone formation of the skull was ongoing, leading to narrowing of the intracranial space and foramen magnum. A large bilateral frontoparietal craniotomy and decompression of the foramen magnum resulted in almost complete relief of his symptoms. This is the first report on successful decompressive surgery as a treatment of cognitive impairment and dysaesthesia.

In 1993 the Netherlands Society for Neurosurgery started a yearly event, a "Quality Conference", specifically devoted to continuous medical education (CME). These conferences differ from "normal" scientific meetings, in the choice for specific topics, in the preparation with inquiries among all the Dutch neurosurgical centres, and in the way the results of these inquiries are discussed, preceded by lectures concerning the chosen topic by guest faculty and Dutch neurosurgeons. Each year's principal guest delivers the "Beks Lecture", named after the former professor in Neurosurgery in Groningen, Jan Beks. On several occasions, the foreign guests suggested to present this format for a larger neurosurgical forum. Therefore, it was decided to describe the various aspects of this format for CME in the Netherlands in a paper for Acta Neurochirugica. Examples of topics are given, a summary of two recent inquiries are presented and discussed, and the way of organizing such a conference including finance and the obligatory character are described.

Background: We studied the use of (201)Thallium SPECT and L-[1-(11)C]-tyrosine PET in patients with a primary glioblastoma multiforme treated with (192)Ir brachytherapy after surgery and external beam radiation therapy. We hypothesised that the patients most likely to benefit from further surgery after deterioration would be those with radiation necrosis and would be recognised by a negative emission tomography scan., Methods: Twenty-one patients underwent (201)Thallium SPECT performed before brachytherapy, and this was repeated in 19 patients when recurrence was suspected. Nine patients also underwent a PET scan at the same time. Nine patients underwent a second operation., Findings: SPECT and PET were highly concordant concerning the prediction of radionecrosis and/or tumour recurrence. Repeat surgery did not lead to a significant increase in survival. There was no significant association between the duration of survival and tumour-to-background ratio but the number studied was small. Both SPECT and PET showed highly active lesions, which were proved to be recurrent tumour by clinical and histological follow-up., Conclusion: Although PET and SPECT are both highly sensitive in detecting active tumour tissue, emission tomography was not clinically valuable in the investigation of patients with a primary glioblastoma treated with brachytherapy.

The development of brain necrosis is life-long risk of repeat radiation therapy, even after a long time interval and a moderate radiation dose. We report on a 34-year-old patient who had prophylactic cranial irradiation with 25Gy and adjuvant chemotherapy in childhood for leukaemia and in adulthood, 28 years later, therapeutic radiotherapy with 54Gy for an atypical (WHO grade II) meningioma. About 2 years later he developed a contrast-enhancing lesion on MRI-scan that was indicative of a tumor according to a thallium-201 ((201)Tl) SPECT scan. Histopathology of the operated contrast-enhancing lesion showed extensive radionecrosis. Radiation necrosis is a small but serious risk after repeat radiation therapy, even after a very long-term interval, the delivery of small fractions and an average cumulative total dose. Patients undergoing repeat radiotherapy therefore need to be followed life-long for potential late radiation toxicity.

Three patients, aged 2, 2.5 and 24 years, presented with a skin lesion in the median or paramedian area at the nose, in the lumbar region and between the shoulders, respectively. The first patient suffered from recurrent infection, the skin lesion of the second patient was a coincidental finding, and the third patient had cosmetic problems. Although there were no signs of neurological deficits, neurodermal closing defects were found by MRI. Two patients underwent surgery to prevent infection and neurological complaints in the future. It is stressed that even if there are no neurological signs or infections, congenital dermal lesions situated in the midline should be considered as possible neural tube defects and therefore analysed by MRI. Ifa neurodermal dysraphism is found, patients should be referred to a neurosurgical centre. A good clinical assessment of the neural lesion, clinical signs and age will determine whether surgical resection is indicated to prevent or resolve neurological problems, infections or cosmetic complaints.

Purpose: Thermoradiotherapy has been shown in several randomized trials to increase local control compared to radiotherapy alone. The first randomized study of interstitial hyperthermia in glioblastoma multiforme showed a survival benefit for hyperthermia, though small. Improvement of the heating technique could lead to improved results. The purpose of this feasibility study is to present the clinical and thermal data of application of an improved interstitial hyperthermia system., Methods and Materials: Six patients with a glioblastoma multiforme were treated with interstitial hyperthermia using the Multi Electrode Current Source Interstitial Hyperthermia (MECS-IHT) system. The MECS-IHT system has the capability of spatial monitoring of temperature and individually steering of heating electrodes. Three sessions were given aiming at a steady state temperature of 42 degrees C for 1 h, with an interval of 3-4 days, during an external irradiation scheme of 60 Gy in 6 weeks. Hyperthermia was delivered with a mean of 10 catheters, 18 heating electrodes and 38 thermal probes per patient., Results: Sub-optimal temperatures were encountered in the first two patients leading to adjustments in technique thereafter with subsequent improvement of thermal data. With a catheter spacing of 11-12 mm, measurements yielded a mean T(90), T(50) and T(10) of 39.9, 43.7 and 45.2 degrees C, respectively, over three sessions in the last patient. The power per electrode to reach this temperature distribution varied from 25-100% of full power in each of the last four patients. Thermal data were reproducible over the three sessions. Acute toxicity was minimal., Conclusions: Despite the spatial steering capabilities of the MECS-IHT system, a large temperature heterogeneity was encountered. The heterogeneity was the reason to limit the catheter spacing to 11-12 mm, thus making only small tumour volumes feasible for interstitial heating.

As quality of life (QoL) is perhaps the most important outcome for patients treated for glioblastoma multiforme (GBM), we measured QoL in GBM patients after brachytherapy. QoL was assessed by questionnaires for both patients and partners before brachytherapy and at various times during follow-up in 21 GBM patients by an extension of the Rotterdam Symptom Checklist (e-RSCL), consisting of four subscales. The Karnofsky Performance Scale (KPS) was also measured. Analysis of variance was done to evaluate the direct effect of brachytherapy (visit 1-2, short-term) and during follow up (visit 1-4, longer-term). Significant short-term effects were found for two subscales of the e-RSCL. Longer-term effects were found for all four subscales and for the KPS. A high correlation between partner and patient's QoL assessment was found. QoL in GBM patients after brachytherapy can therefore be carefully monitored with a subjective instrument such as the e-RSCL. Patients and partners experience QoL equally.

We report of a large epidermoid tumor of the lateral ventricle in a 67-year-old man. Conventional imaging (CT, T1/T2, MRI) could not differentiate the tumor from the surrounding cerebral spinal fluid (CSF). On diffusion-weighted and diffusion anisotropy images the tumor was clearly seen as a hyperintense mass surrounded by hypointense CSF, highly suspected for epidermoid. Diffusion-tensor imaging (DTI) accentuated its lobulated structure and clearly demonstrated its relationship to neighboring white matter tracts. We suggest that in case of the suspicion of a space-occupying lesion in CSF containing areas, not distinguishable from CSF by conventional MR imaging, diffusion-weighted and diffusion-tensor MR imaging should be added.

Background: To analyze prognostic factors in patients with a glioblastoma multiforme treated in an academic institute over the last 10 years., Patients and Method: From 1988 to 1998, 198 patients with pathologically confirmed glioblastoma multiforme were analyzed. Five radiation schedules were used mainly based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an interstitial iridium-192 (Ir-192) boost for selected patients with a good performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions for poor prognostic patients and 5. no irradiation., Results: Median survival was 16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively. No significant improvement in survival was encountered over the last 10 years. At multivariate analysis patients treated with a hypofractionated scheme showed a similar survival probability and duration of palliative effect compared to the conventionally fractionated group. The poor prognostic groups receiving radiotherapy had a highly significant better survival compared to the no-treatment group. Patients treated with an Ir-192 boost had a better median survival compared to a historical group matched on selection criteria but without boost treatment (16 vs 9.7 months, n.s.). However, survival at 2 years was similar. Analysis on pretreatment characteristics at multivariate analysis revealed age, neurological performance, addition of radiotherapy, total resection, tumor size post surgery and deterioration before start of radiotherapy (borderline) as significant prognostic factors for survival., Conclusion: Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors corresponded well with data from the literature. A short hypofractionated scheme seems to be a more appropriate treatment for patients with intermediate or poor prognosis as compared to a conventional scheme. The benefit in median survival for patients treated with an interstitial boost is partly explained by patient selection. Since there were no long-term survivors with this boost treatment, its clinical value, if there is one, is still limited.

Background: In the current study, the authors describe and compare two different strategies of brachytherapy for the treatment of patients with primary glioblastoma multiforme (GBM)., Methods: The study was comprised of 84 patients. Forty-five patients were implanted with permanent or temporary low activity iodine-125 ((125)I) seeds in Cologne and 21 patients were implanted with temporary iridium-192 ((192)Ir) wires in Amsterdam. Both groups received external beam radiation therapy (EBRT); the (125)I group received 10-30 grays (Gy) with the implant in situ and the (192)Ir group received 60 Gy before implantation. In Cologne, implantation was performed after a diagnostic stereotactic biopsy whereas in Amsterdam implantation took place after cytoreductive diagnostic surgery. In addition, 18 patients in Amsterdam served as a control group. This group received only EBRT after cytoreductive surgery., Results: In both groups the mean age of the patients was between 50-55 years, with 80% of the patients age > 45 years. The mean implantation volume encompassed by the referenced isodose was 23 cm(3) for (125)I and 48 cm(3) for (192)Ir. Initial dose rates were 2. 5-2.9 centigrays (cGy)/hour for permanent (125)I, 4.6 cGy/hour for temporary (125)I, and 44-100 cGy/hour (mean, 61 cGy) for (192)Ir. A total dose of 50-60 Gy, 60-80 Gy, and 40 Gy, respectively, was administered at the outer margins of the tumor. The median survival was approximately 16 months for both the (125)I group and the (192)Ir group. This was 6 months longer than the median survival in the control group. Reoperations were performed in 4 patients in the (125)I group (9%) versus 7 patients in the (192)Ir group (33%). No complications or late reactions were reported in the (125)I group, whereas one case of hemorrhage and three cases of delayed stroke were observed in the (192)Ir group., Conclusions: The equal median survival times in these two brachytherapy groups with such different dose rate radiation schedules support the hypothesis that dose rate does not play a major role in the survival of patients with primary GBM., (Copyright 2000 American Cancer Society.)

A new template technique has been developed for implanting hyperthermia catheters in the treatment of brain tumors. The technique utilizes an imaging template and a drill template which can be rigidly secured to the head with three skull screws. The anatomic and vascular information needed for hyperthermia treatment planning may be assessed with three-dimensional magnetic resonance (MR) imaging and angiography acquisitions which use a surface coil. In the companioning treatment planning system the catheter positions and lengths and the electrodes in the catheter can be interactively manipulated relative to the anatomy and vasculature. The visualization of the blood vessels relative to the template allows the minimization of the risk on intracranial hemorrhages. This template technique is useful for any brain tumor implants, especially when a large number of catheters are involved. A phantom test has shown that this procedure has an accuracy in the order of 1 mm provided that the MR-related geometry distortions are minimized.

Two patients, a woman aged 65 years and a man aged 56 years, with cancer, presented with pain in one leg as the first manifestation of metastases. The woman had tumour plexopathy of the lumbosacral plexus caused by an os sacrum metastasis of a thyroid carcinoma; she received radiotherapy but died a short time later. The man had lumbosacral epidural metastases of a colon carcinoma, compressing lumbosacral roots; with radiotherapy he survived the first year. Back pain with radiating pain is a frequent symptom in patients with cancer. Spinal epidural metastases, spinal and paraspinal metastases without epidural extension, tumour plexopathy and leptomeningeal metastases are the commonest causes. Early diagnosis (by MRI or spinal fluid examination) is important; with progressive weakness or sphincter disturbances the prognosis worsens.

Two children were presented with a torticollis. One, a 2-year-old girl, had a primitive neuroectodermal tumour of the cervical spinal cord which could not be radically removed surgically (the patient died three days later), the other, a 9-year-old boy, had the syndrome of Grisel. He was treated with antibiotics, head traction and atlantoaxial posterior spondylodesis. Acquired torticollis is a frequent innocent symptom in children with cervical lymphadenopathy following a respiratory tract infection. These cases demonstrate that additional investigation should not be delayed if relief of symptoms is not achieved very soon.

HMG-CoA reductase inhibitors (statins), cholesterol-lowering drugs that have not been approved for use in children and adolescents, may cause myopathy as a side effect. We compared the effects of three statins (simva-, prava- and lovastatin) in young rats to determine whether skeletal muscle of young animals is more susceptible than that of adults. We also evaluated whether the type of statin (lipophilic versus hydrophilic) determines the degree of muscle damage. Administration via chow of simvastatin (15 mg/kg of body weight/d) and lovastatin (43-55 mg/kg of body weight/d), both lipophilic, caused stunted growth, high creatine kinase (CK) activity in plasma, and severe myopathy. Statin doses that caused damage were much lower for young rats than for adults. Pravastatin (8-55 mg/kg of body weight/d), a hydrophilic drug, caused none of these symptoms. Histologic analysis of hind paw muscles of simvastatin-and lovastatin-treated rats showed abundant signs of damage (hypercontraction, fiber necrosis) in the extensor digitorum longus, correlating with the symptoms noted above. No cellular infiltrates were seen at the onset, pointing to a noninflammatory myopathy. Pravastatin-treated rats never showed signs of myopathy. Impaired DNA synthesis may explain why muscle toxicity is seen at lower doses in young, rapidly developing rats than in adult animals. The differences in muscle damage between the statins may be attributed to differences in lipophilicity and thus in tissue selectivity. Our results can be important when considering drug therapy in young patients with inherited lipoprotein disorders.

Background: Up to 60% of the patients with known adenomatous polyposis coli may present hyperostosis of the skull and facial bones, and/or a susceptibility to fibromas. This is known as the Gardner's syndrome, and is considered as an allelic variant of familial adenomatous polyposis (FAP). Also, although very rare, an adenomatous polyposis coli may occur with malignant tumors of the central nervous system, known as Turcot syndrome. If both syndromes are different phenotypic presentation of FAP, this would explain a simultaneous occurrence., Method: We report the history of a patient who showed clinical signs of the simultaneous occurrence of both Gardner's and Turcot syndromes. The syndromes are compared, and in view of the literature, a genetic explanation for the concomitant occurrence is discussed., Results: Evidence obtained from the literature to consider Turcot syndrome as a phenotype of FAB is as follows: (1) The occurrence of Gardner's and Turcot syndromes in one family, but in different members; (2) The presence of congenital hypertrophic retinal pigmented epithelium (CHRPE), which correlates with the expression of polyps in FAP patients, in both syndromes; (3) Linkage of the Turcot phenotype to the adenomatous polyposis coli locus by genetic markers. Evidence obtained from this case report indicates that there is a manifestation of both syndromes in one patient together with a positive family history for FAP., Conclusion: This concomitant occurrence of both Gardner's and Turcot syndromes in one patient clinically supports genetic and ophthalmic investigation to consider Turcot syndrome (like Gardner's syndrome) as a phenotypic variant of FAP. Patients with FAP should be examined for the presence of Gardner's syndrome. In case a Gardner's syndrome is suspected, a computed tomography scan of the brain is recommended because of the possible existence of a simultaneous Turcot syndrome.

Objective: Evaluation of incidence, treatment and outcome of multiple injuries in children and adults., Method: All patients aged 16 years or under with an Injury Severity Score of 18 or more admitted to the Intensive Care Unit between 1984 and 1991, were retrospectively studied. Type and severity of injuries, treatment, complications and outcome were noted. The severity of injuries was scored using both the Injury Severity Score and the Paediatric Trauma Score., Results: Children are more likely to be run over by motor vehicles. Rib fractures are rare in childhood. Compared with adults, children stay relatively shortly in the Intensive Care Unit. None of the children studied developed a Respiratory Distress Syndrome (RDS) or Multi-Organ Failure (MOF). External fixation of fractures is a common treatment in children., Conclusions: I. Outcome of multiple injuries in children is relatively good. This can partly be attributed to the low incidence of RDS and MOF, but also to the more common diffuse brain injury in children compared with adults, with better outcome and lower mortality. 2. External fixation of fractures appears to be a first rate treatment in children. 3. Scoring of multiple injuries in children with the Paediatric Trauma Score instead of the Injury Severity Score offers no advantages.

Tamoxifen (TX), an oestrogen antagonist, was used to characterize the protective effect of oestradiol (E2) on exercise-related creatine kinase (CK) release from skeletal muscle of the rat. Subcutaneous administration of TX for 3 weeks in female rats had a profound antioestrogen effect as evidenced by a reduced weight of the uterus. The CK release after electrical stimulation of the isolated soleus muscle, previously shown to be E2-dependent, was markedly reduced (30-50%) after treatment with TX; this observation points to an E2-like protective action of TX instead of E2-antagonism. This effect was dose-dependent (0.25-1.00 mg/kg) and was not seen when TX was given shortly (24 h) before the experiments. In ovariectomized females, that show more CK leakage due to the lack of circulating E2, both E2- and TX-treatment resulted in a 60% reduction of the CK leakage. Muscles from male rats, treated with TX, showed a similar response: after contractions the CK release was significantly lower. We conclude that TX, like E2, reduces contraction-induced muscle damage in the rat and, thus, has E2-agonistic properties on skeletal rat muscle.

Creatine kinase (CK) release from male and female rat soleus muscles was studied for 4.5 h in vitro, under basal conditions and after electrical stimulation. Basal CK release was greater from male than from female muscles, and CK release from male muscles increased significantly when the muscle tension in the in-vitro set-up was increased. CK release after electrical stimulation was also more marked in male soleus muscles. Pretreatment of male rats and ovariectomized female rats with oestradiol for 3 weeks attenuated the enzyme efflux, but ovariectomy 24 h before in females, or oestradiol administration 24 h before in males, did not affect the release of CK in vitro. The data show that sex-linked differences in CK efflux are still present, under both basal and stimulated conditions, when muscles are isolated from the intact animal, and that hormone treatment of the intact animal affects these properties in the isolated muscle in vitro.