Long-term follow up of patients with WHO grade 2 oligodendroglioma.

PURPOSE: Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival. METHODS: All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival. RESULTS: 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0-19.6). Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02-1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02-1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70-11.78, p = 0.002). In our material, surgical strategy was not associated with survival. CONCLUSION: Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival.

Standardized reporting of adverse events and functional status from the first 5 years of awake surgery for gliomas: a population-based single-institution consecutive series.

OBJECTIVE: To report our experience and investigate frequencies of adverse events and functional status from the first 5 years of performing awake surgery for gliomas in a single-center population-based setting. METHODS: We conducted a review of all patients with a glioma treated with awake surgery during the first 5 years following introduction of awake surgery at our center (February 2015 to February 2020). We assessed functional and radiological outcome, with adverse events classified according to the Landriel-Ibanez classification for neurosurgical complications, while neurological deficits were further subdivided into transient vs permanent. We sought to analyze our initial results and learning curve, as well as compare our results with literature. RESULTS: Forty-two patients were included. The median age was 38 years (range 18-66) and 13 (31%) were female. The indication for awake surgery was a presumed glioma in or near an eloquent area. The overall 30-day complication rate was 25 (59%), with 19 (45%) grade I complications, 3 (7%) grade II complications, and 3 (7%) grade III complications. Fifteen patients (36%) experienced transient neurological deficits, and 11 (26%) permanent neurological deficits. At 3-month follow-up, the Karnofsky Performance Score was 80 or higher for the entire cohort. The median extent of resection was 87%, with GTR achieved in 11 (26%). In search of potential learning curve difficulties, patients were divided into the 21 patients treated first (Early Group) versus the remaining 21 patients treated later (Late Group); no statistically significant difference in operating time, amount of tumor removed, or incidence of long-term postoperative neurological deficit was identified between groups. No awake surgery was aborted due to seizures. Comparison to the literature was limited by the diverse and unsystematic way in which previous studies have reported adverse events after awake craniotomy for gliomas. CONCLUSION: We provide a standardized report of adverse events and functional status following awake surgery for glioma during a single-center 5-year learning period, with similar rates of severe adverse events and functional outcome compared to literature without concerns of substantial learning curve difficulties. However, this comparison was flawed by non-standardized reporting of complications, highlighting a demand for more standardized reporting of adverse events after awake craniotomies.

Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher's Disease Type 3.

BACKGROUND: Chronic neuronopathic Gaucher's disease type 3 (GD3) is relatively frequent in northern Sweden. Besides multiple other neurological symptoms, horizontal gaze palsy or oculomotor apraxia is common in GD3. OBJECTIVE: To characterize the saccades in patients with Norrbottnian GD3 with respect to their neurological and cognitive status using a computer-based eye-tracking technique. METHODS: Horizontal and vertical reflexive saccades as well as antisaccades of nine GD3 patients [4M/5F; 41.1 ± 11.0 years; modified severity scoring tool (mSST): 9.3 ± 5.4; Montreal Cognitive Assessment (MoCA): 24.0 ± 4.2] and age-matched controls were analyzed using EyeBrain T2, a head-mounted binocular eye tracker. Systematic clinical assessment included the mSST, a valid tool for monitoring the neurological progression in GD3 and MoCA. RESULTS: In Norrbottnian GD3 patients, gain, peak, and average velocity (107.5°/s ± 41.8 vs. 283.9°/s ± 17.0; p = 0.0009) of horizontal saccades were reduced compared to healthy controls (HCs). Regarding vertical saccades, only the average velocity of downward saccades was decreased (128.6°/s ± 63.4 vs. 244.1°/s ± 50.8; p = 0.004). Vertical and horizontal saccadic latencies were increased (294.3 ms ± 37.0 vs. 236.5 ms ± 22.4; p = 0.005) and the latency of horizontal reflexive saccades was correlated with the mSST score (R2 = 0.80; p = 0.003). The latency of antisaccades showed association to MoCA score (R2 = 0.70; p = 0.009). GD3 patients made more errors in the antisaccade task (41.5 ± 27.6% vs. 5.2 ± 5.8%; p = 0.005), and the error rate tended to correlate with the cognitive function measured in MoCA score (p = 0.06). CONCLUSION: The mean age of 41 years of our GD3 cohort reflects the increased life expectancy of patients in the Norrbottnian area compared to other GD3 cohorts. Marked impairment of horizontal saccades was evident in all patients, whereas vertical saccades showed distinct impairment of downward velocity. Latency of reflexive saccades was associated with the severity of neurological symptoms. Increased latency and error rate in the antisaccade task were linked to cognitive impairment. The assessment of saccades provides markers for neurological and neuropsychological involvement in Norrbottnian GD3.

PSP-CBS with Dopamine Deficiency in a Female with a FMR1 Premutation.

Premutations in the fragile X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR1-related primary ovarian insufficiency (POI). Female FMR1 premutation carriers rarely develop motor features. Dual pathology is an emerging phenomenon among FMR1 premutation carriers. Here, we describe a family affected by FMR1-related disorders in which the female index case has developed a rapidly progressive and disabling syndrome of atypical parkinsonism. This syndrome consists of early onset postural instability, echolalia, dystonia, and varying types of apraxia like early onset orobuccal apraxia and oculomotor apraxia. She has also developed supranuclear gaze palsy, increased latency of saccade initiation, and slow saccades. These features are compatible with progressive supranuclear palsy (PSP) of a corticobasal syndrome (CBS) variant. Imaging displays a marked reduction of presynaptic dopaminergic uptake and cerebrospinal fluid analysis showed reduced dopamine metabolism; however, the patient is unresponsive to levodopa. Midbrain atrophy ("hummingbird sign") and mild cerebellar atrophy were found on brain MRI. Her father was affected by a typical FXTAS presentation but also displayed dopamine deficiency along with the hummingbird sign. The mechanisms by which FMR1 premutations predispose to atypical parkinsonism and dopamine deficiency await further elucidation.