Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial.

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.

A prediction model for recurrence after translabyrinthine surgery for vestibular schwannoma: toward personalized postoperative surveillance.

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.

Decompressive surgery in a patient with hyperostosis corticalis generalisata for relief of cognitive disability and dysaesthesia.

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.

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

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.

Long-Term Quality of Life of Vestibular Schwannoma Patients: A Longitudinal Analysis.

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.

Vestibular Complaints Impact on the Long-Term Quality of Life of Vestibular Schwannoma Patients.

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.

The Course of Hearing Loss in Patients With a Progressive Vestibular Schwannoma.

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, R2 = 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.

Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial.

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 six months. An expected proportion of the included patients had non-aneurysmal 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 six 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 non-contrast computer tomography, 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 six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome. RESULTS: Of the 813 ULTRA-trial patients who had 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% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52). DISCUSSION: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24th, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

Prognostic Factors for the Outcome of Translabyrinthine Surgery for Vestibular Schwannomas.

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.

Nadroparin Plus Compression Stockings versus Nadroparin Alone for Prevention of Venous Thromboembolism in Cerebellopontine Angle Tumour Excisions: A Cohort Study.

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.

[Hearing without ears]. / Horen zonder oren.

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.

Pediatric Auditory Brainstem Implant Users Compared With Cochlear Implant Users With Additional Disabilities.

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.

Dexamethasone therapy versus surgery for chronic subdural haematoma (DECSA trial): study protocol for a randomised controlled trial.

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.

Cerebral necrosis after 25Gy radiotherapy in childhood followed 28 years later by 54Gy radiotherapy.

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.

Epidermoid of the lateral ventricle: evaluation with diffusion-weighted and diffusion tensor imaging.

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.