Search

BackgroundThe Phase 1/2 Treat_CCM randomized controlled trial for people with familial cerebral cavernous malformations (FCCMs) confirmed the safety of propranolol and suggested beneficial effects on intracerebral hemorrhage or new focal neurological deficits, but the effects on patient-reported outcome measures have not been reported.MethodsParticipants completed self-reported questionnaires at baseline, 1 and 2 years. Depression was assessed with the Beck Depression Inventory-II (BDI-2); Anxiety with the State–Trait Anxiety Inventory X1 and X2 (STAI X-1 and STAI X-2); and Quality of Life with the Short Form 36 (SF-36), split into the physical and mental component scales (PCS and MCS). Differences between treatment groups and the general population were assessed. Change over time by treatment was assessed by means of mixed models.ResultsIn total, 71 participants (48 propranolol and 23 standard care) were enrolled, of whom 61 (73%) completed questionnaires at baseline and 2-year FU. At baseline, no differences between treatment groups for any of the questionnaires were present. Twenty (31.7%) patients were considered depressed at baseline, while this proportion was lower in the propranolol group after 2 years (28.6% vs. 55.5%, p = 0.047). The STAI X-1 and X-2 scores were stable over time. PCS was lower in FCCM patients as compared with the general Italian population, while the MCS was similar to the general population. No effect of propranolol was found for both PCS and MCS.ConclusionDepression is common among patients with FCCM. Patients randomized to propranolol had a lower proportion of participants with depression after 2 years.Clinical trial registration: https://clinicaltrials.gov/, identifier (NCT03589014).

Diffusion tensor imaging (DTI) allows visualization of the main white matter tracts while intraoperative neurophysiological monitoring (IONM) represents the gold standard for surgical resection of gliomas. In recent years, the use of small craniotomies has gained popularity thanks to neuronavigation and to the low morbidity rates associated with shorter surgical procedures. The aim of this study was to review a series of patients operated for glioma using DTI, IONM, and tumor-targeted craniotomies. The retrospective analysis included patients with supratentorial glioma who met the following inclusion criteria: preoperative DTI, intraoperative IONM, tumor-targeted craniotomy, pre- and postoperative MRI, and complete clinical charts. The DTI was performed on a 3T scanner. The IONM included electroencephalography (EEG), transcranial (TC) and/or cortical motor-evoked potentials (MEP), electrocorticography (ECoG), and direct electrical stimulation (DES). Outcomes included postoperative neurological deficits, volumetric extent of resection (EOR), and overall survival (OS). One hundred and three patients (61 men, 42 women; mean age 54 ± 14 years) were included and presented the following WHO histologies: 65 grade IV, 19 grade III, and 19 grade II gliomas. After 3 months, only three patients had new neurological deficits. The median postoperative volume was 0cc (IQR 3). The median OS for grade IV gliomas was 15 months, while for low-grade gliomas it was not reached. In our experience, a small craniotomy and a tumor resection supported by IONM and DTI permitted to achieve satisfactory results in terms of neurological outcomes, EOR, and OS for glioma patients.

Abstract Background Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression. Methods Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40–80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory). Discussion Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial. Trial registration ClinicalTrails.gov, NCT03589014 . Retrospectively registered on 17 July 2018.

Introduction Although it was a giant leap forward when it was introduced, the classic approach to the norming of neuropsychological tests (Capitani, 1987) has two main limitations: (i) it doesn’t consider possible interactions between covariates (e.g., age and education); (ii) working on by–subject percentages of correct responses, it cannot consider item covariates (e.g., frequency, length, imageability) that are known to affect performance substantially. Here we show how to overcome these limitations, and how this improves our diagnosis. Methods As a test case, we used the action–naming task devised by Crepaldi et al. (2006). 290 healthy Italian speakers (148 F and 142 M) made up our norming sample. They ranged 18 to 98 years in age (M=54.1) and 3 to 23 years in education (M=12.3). The test was standardized: (i) following the classic Capitani approach, based on regressing by–subject mean accuracy on gender, age and education; (ii) adding interactions between gender, age and education to the classic approach; (iii) using raw correct/incorrect scores thanks to mixed–effect models, thus being able to take under control also item variables (e.g., frequency, imageability) and any additional item– or subject–specific random variability (mixed–effects norming; Jaeger, 2008). Results We first contrasted the three approaches in terms of their amount of explained variance in the computation of expected scores, that is, their ability to “wash out” unwanted effects from expected scores. The classic Capitani norming explained 34.7% of the total variance; interaction norming went up to 43.7%; and mixed–effects norming ensured 73% of explained variance. A comparison between expected scores according to Capitani and mixed–effects norming in 2,600 combinations of age (20–85) and education values (3-22) revealed an overall correlation of .81. Differences were generally bigger with young age and low education, and with old age and high education; and typically showed higher expected scores by mixed–effects than Capitani norming (see Figure 1). Equivalent Scores (ES) were then computed for a simulated sample of around 80,000 patients ranging in age (20–85 years), education (3–22 years), gender (M–F) and raw scores (20–50 correct responses). They disagree 28% of the times according to the two approaches. The difference (in either direction) is 1.28 in mean, and ranges from 1 to 4. Mixed–effects ES is lower than Capitani ES in 61% of the cases. Among the 45070 simulated patients that would be classified as impaired at naming verbs (ES=0) according to Capitani norming, 5% would not be classified as such (ES>0) according to mixed–effects norming. These figures are closely replicated in a sample of 69 unselected aphasic patients. Discussion The data indicate that using a better statistical model to calculate expected scores is highly beneficial in terms of amount of explained variance, that is, we can gauge the true effects of subject (e.g., age) and item variables (e.g., frequency) much more precisely, thus enjoying higher–quality corrected scores. Critically, this reflects substantially into how (simulated and actual) patients are classified.