Leber Hereditary Optic Neuropathy Case Report: Clinical Presentation and Treatment with Idebenone Reinforce the Evidence for m.3866T>C as a Causative Variant.

Introduction: Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder that typically presents with painless, central visual loss, hyperaemia of the optic nerve head, and peripapillary telangiectasias. Most LHON cases are due to one of three variants, but several less common variants also exist. We describe a clinical case of LHON associated with the variant m.3866T>C, which is possibly linked to LHON. Case Presentation: A 59-year-old Caucasian woman experienced acute, bilateral, and painless visual loss. She reported cigarette smoking, and elevated phosphatidylethanol suggested harmful alcohol consumption. Her best-corrected visual acuity (BCVA) was 20/100 for the right eye and 20/50 for the left eye. She could only read the Ishihara demonstration plate, and threshold perimetry demonstrated reduced central sensitivity bilaterally. Her optic nerve heads were hyperaemic, with peripapillary telangiectasias. The visual symptoms and clinical findings suggested LHON. Magnetic resonance imaging demonstrated a tuberculum sella meningioma and two cerebral aneurysms, which we regarded as incidental findings. Genetic testing did not identify common LHON variants but a rare homoplasmic variant, m.3866T>C, which studies suggest might cause LHON or act in synergy with other variants to increase the disease penetrance. After initiating test-of-treatment with idebenone 900 mg per day, the patient's BCVA improved to 20/32 for both eyes and then stabilized. Conclusion: This case strengthens the evidence for m.3866T>C as a causative LHON variant. The case also raises the question as to whether this particular variant can respond favourably to treatment with idebenone.

The benefit of complete resection of contrast enhancing tumor in glioblastoma patients: A population-based study.

Background: New treatment modalities have not been widely adopted for patients with glioblastoma (GBM) after the addition of temozolomide to radiotherapy. We hypothesize that increased extent of resection (EOR) has resulted in improved survival for surgically treated patients with glioblastoma at the population level. Methods: Retrospective analysis of adult patients operated for glioblastoma in the population of South-Eastern Norway. Patients were stratified into Pre-temozolomide- (2003-2005), temozolomide- (2006-2012), and resection-focused period (2013-2019) and evaluated according to age and EOR. Results: The study included 1657 adult patients operated on for supratentorial glioblastoma. The incidence of histologically confirmed glioblastoma increased from 3.7 in 2003 to 5.3 per 100 000 in 2019. The median survival was 11.4 months. Complete resection of contrast-enhancing tumor (CRCET) was achieved in 386 patients, and this fraction increased from 13% to 32% across the periods. Significant improvement in median survival was found between the first 2 periods and the last (10.5 and 10.6 vs. 12.3 months; P < .01), with a significant increase in 3- and 5-year survival probability to 12% and 6% (P < .01). Patients with CRCET survived longer than patients with non-CRCET (16.1 vs. 10.8 months; P < .001). The median survival doubled in patients ≥70 years and (12.1 months). Survival was similar between the time periods in patients where CRCET was achieved. Conclusions: We demonstrate an improved survival of GBM patients at the population level associated with an increased fraction of patients with CRCET. The data support the importance of CRCET to improve glioblastoma patient outcomes.

Early surgical versus endovascular repair of ruptured blood-blister aneurysm of the internal carotid artery: a single-center 20-year experience.

OBJECTIVE: Early repair of ruptured blood-blister aneurysms (BBAs) of the internal carotid artery (ICA) remains challenging. Although both surgical and endovascular therapies have been established, their relative superiority remains debated. The authors assessed their single-center experience and compared early deconstructive versus reconstructive repair and early reconstructive surgical versus endovascular repair of ruptured BBAs of the ICA. METHODS: The study included patients who underwent repair of ruptured BBAs of the ICA within 1 week after the ictus during a 20-year period. Multiple variables were recorded, including clinical state, severity of subarachnoid hemorrhage (SAH), characteristics of the BBA, treatment details, complication profile, need for secondary treatment, and clinical outcome. RESULTS: In total, 27 patients underwent early surgical (n = 16) or endovascular (n = 11) repair of BBAs at a median of 24 hours (range 9-120 hours) after the ictus during the period from September 2000 to June 2021 (20.4 years). Primary deconstructive repair (n = 6) without bypass was accompanied by middle cerebral artery (MCA) territory infarction in 5 of 6 (83%) patients and a high mortality rate (4/6 [67%]). Among the 21 patients who underwent early reconstructive repair, surgery was performed in 11 patients (clipping in 6 and clip-wrapping in 5 patients) and endovascular repair in 10 patients (flow diversion in 7 and stent/stent-assisted coiling in 3 patients). No differences were found in complication profiles or clinical outcomes between the surgical and endovascular groups. The mortality rate was low (2/21 [9.5%]), with 1 fatality in each group. CONCLUSIONS: From the authors' experience, both surgical and endovascular approaches permitted reconstructive repair of ruptured BBAs of the ICA, with no modality proving superior. Reconstructive treatment is preferable to ICA sacrifice, and if sacrifice is chosen, it should be accompanied with bypass surgery or delayed to the phase when cerebral vasospasm has resumed. The rare occurrence of this disease calls for prospective multicenter studies to improve treatment and delineate which modality is preferable in individual cases.

External validation of a prognostic model for early mortality after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of lost disability-adjusted life years, and a valid model allowing prediction of outcome would be welcome. For a clinical prediction model to be valid, generalization to other populations must be possible. The aim of this study was to externally validate a model for in-hospital mortality in patients with TBI, which was recently development at the University of Southern California (USC). METHODS: The validation cohort was derived from a hospital-based, prospectively collected trauma registry in Oslo, Norway. We included patients admitted with a head injury without hypotension, severe thoracic, or abdominal injury (n = 3,136). We calculated the probability of death according to the USC model. The performance of the model was evaluated using measures of calibration and discrimination in the total sample and subgroups according to initial Glasgow Coma Scale (GCS) score. RESULTS: The USC model provided excellent discrimination (area under the receiver operating characteristic curve, AUC = 0.93), but unsatisfactory calibration (p < 0.001) for the total sample (GCS 3-15). In the GCS 4-8 subgroup we found good discrimination (AUC = 0.89) but poor calibration (Hosmer-Lemeshow test, p < 0.001). CONCLUSION: The findings question the external validity of the USC model, suggesting that it should not be implemented as a tool for short-term mortality prediction in our TBI population.

The effect of pregnancy on survival in a low-grade glioma cohort.

OBJECTIVE The impact of pregnancy on survival in female patients with low-grade glioma (LGG) is unknown and controversial. The authors designed a retrospective cohort study on prospectively collected registry data to assess the influence of pregnancy and child delivery on the survival of female patients with LGG. METHODS In Norway, the reporting of all births and cancer diagnoses to the Medical Birth Registry of Norway (MBRN) and the Cancer Registry of Norway (CRN), respectively, is compulsory by law. Furthermore, every individual has a unique 11-digit identification number. The CRN was searched to identify all female patients with a histologically confirmed diagnosis of World Health Organization (WHO) Grade II astrocytoma, oligoastrocytoma, oligodendroglioma, or pilocytic astrocytoma who were 16-40 years of age at the time of diagnosis during the period from January 1, 1970, to December 31, 2008. Obstetrical information was obtained from the MBRN for each patient. The effect of pregnancy on survival was evaluated using a Cox model with parity as a time-dependent variable. RESULTS The authors identified 65 patients who gave birth to 95 children after an LGG diagnosis. They also identified 281 patients who did not give birth after an LGG diagnosis. The median survival was 14.3 years (95% CI 11.7-20.6 years) for the entire study population. The effect of pregnancy was insignificant in the multivariate model (HR 0.71, 95% CI 0.35-1.42). CONCLUSIONS Pregnancy does not seem to have an impact on the survival of female patients with LGG.

A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme.

The effect of temozolomide (TMZ) and radiotherapy (RT) in the treatment of glioblastoma multiforme (GBM) has been well documented in randomized controlled trials. Here we present our findings on the effect of TMZ added to RT at a population level. The Cancer Registry of Norway was searched for patients with a GBM diagnosis from January 1, 2000 to December 31, 2007. Subsequently, the prescriptions registered to these patients were obtained from the Norwegian Prescription Database. The data were analyzed according to era (pre-TMZ introduction or post-TMZ introduction) and according to treatment received. Furthermore, a matching procedure was utilized to reduce the bias between the RT + TMZ and RT alone treatments so that the effect of TMZ could be better scrutinized. We identified 1157 GBM patients. The median overall survival (OS), in months, was 8.3 (95% confidence interval: 7.6-9.0) and 10.1 (95% confidence interval: 9.1-11.0) in the pre-TMZ and TMZ eras, respectively (P < .001). By treatment, we found median OS for the control, RT alone, and RT + TMZ groups to be 2.5, 9.0, and 16.2 months, respectively (P < .001). Two-year survival was 0%, 4%, and 25%, respectively. The effect of age on TMZ effect was insignificant. In the matched group analysis, TMZ provided a 7.6-month OS benefit. Our population data reproduce the beneficial effect of TMZ from randomized controlled trials with a median OS of 16.2 months and 25% 2-year survival.