Background Glioma patients suffer from a wide range of symptoms which influence quality of life negatively. The aim of this review is to give an overview of symptoms most prevalent in glioma patients throughout the total disease trajectory, to be used as a basis for the development of a specific glioma Patient Reported Outcome Measure (PROM) for early assessment and monitoring of symptoms in glioma patients. Methods A systematic review focused on symptom prevalence in glioma patients in different phases of disease and treatment was performed in MEDLINE, CINAHL and EMBASE according to PRISMA recommendations. We calculated weighted means for prevalence rates per symptom. Results The search identified 2.074 unique papers, of which 32 were included in this review. In total 25 symptoms were identified. The ten most prevalent symptoms were: seizures (37%), cognitive deficits (36%), drowsiness (35%), dysphagia (30%), headache (27%), confusion (27%), aphasia (24%), motor deficits (21%), fatigue (20%) and dyspnea (20%). Conclusions Eight out of ten of the most prevalent symptoms in glioma patients are related to the central nervous system and therefore specific for glioma. Our findings emphasize the importance of tailored symptom care for glioma patients and may aid in the development of specific PROMs for glioma patients in different phases of the disease.

Deficits in neurocognitive functioning (NCF) frequently occur in glioma patients. Both treatment and the tumor itself contribute to these deficits. Data about the role of the tumor are scarce, because NCF has mostly been studied postoperatively. We aimed to summarize data on pre-treatment NCF in glioma patients and to determine the overall and domain-specific prevalence of neurocognitive dysfunction. We searched PubMed and Embase according to PRISMA-P protocol for studies that evaluated pre-treatment NCF in glioma patients (1995-November 2016) and extracted information about NCF. We performed analysis of data for two main outcome measures; mean cognitive functioning of the study sample (at group level) and the percentage of impaired patients (at individual level). We included 23 studies. Most studies were small observational prospective cohort studies. In 11 (47.5%) studies, patient selection was based on tumor location. NCF was analyzed at the group level in 14 studies, of which 13 (92.9%) found decreased NCF at group level, compared to normative data or matched controls. The proportion of individuals with decreased NCF was reported in 15 studies. NCF was impaired (in any domain) in 62.6% of the individuals (median; interquartile range 31.0–79.0). Cognitive impairments were more common in patients with high-grade glioma than with low-grade glioma (OR 2.50; 95% CI 1.71–3.66). Cognitive impairment occurs in the majority of treatment-naive glioma patients, suggesting that neurocognitive dysfunction is related to the tumor. However, the literature about pre-treatment NCF in glioma patients is characterized by small-scale studies and strong heterogeneity in patient selection, resulting in high risk of bias.

Bing Neel syndrome is a rare disease manifestation of Waldenstrom macroglobulinemia that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells. In this guideline, we describe the clinical symptoms, as well as the appropriate laboratory and radiological studies that can aid in the diagnosis. The presentation of Bing Neel syndrome may be very diverse, and include headaches, cognitive deficits, paresis, and psychiatric symptoms. The syndrome can present in patients with known Waldenstrom macroglobulinemia, even in the absence of systemic progression, but also in previously undiagnosed patients. Diagnostic workup should include cerebral spinal fluid analysis with multiparameter flow cytometry to establish B-cell clonality, protein electrophoresis and immunofixation for the detection and classification of an monoclonal protein, as well as molecular diagnostic testing for immunoglobulin gene rearrangement and mutated MYD88. MRI of the brain and spinal cord is also essential. The second challenge is to expand our knowledge about the prognosis and treatment outcome. Prospective clinical trials in Bing Neel syndrome patients that employ uniform treatment along with appropriate laboratory cerebral spinal fluid assessments and standardized MRI protocols will be invaluable, and provide a significant step forward in delineating treatment outcome for this intriguing disease manifestation.

A scorecard to evaluate magnetic resonance imaging (MRI) findings during the course of leptomeningeal metastases (LM) has been proposed by the Response Assessment in Neuro-Oncology (RANO) group. To explore the feasibility of the Leptomeningeal Assessment in Neuro-Oncology (LANO) scorecard, cerebrospinal MRIs of 22 patients with LM from solid tumors were scored by 10 neuro-oncologists and 9 neuroradiologists at baseline and at follow-up after treatment. Raters were blinded for clinical data including treatment. Agreement between raters of single items was evaluated using a Krippendorff alpha coefficient. Agreement between numerical parameters such as scores for changes between baseline and follow-up and total scores was evaluated by determining the intraclass coefficient of correlation. Most raters experienced problems with the instructions of the scorecard. No acceptable alpha concordance coefficient was obtained for the rating of single items at baseline or follow-up. The most concordant ratings were obtained for spinal nodules. The concordances were worst for brain linear leptomeningeal enhancement and cranial nerve enhancement. Discordance was less prominent among neuroradiologists than among neuro-oncologists. High variability was also observed for evaluating changes between baseline and follow-up and for total scores. Assessing response of LM by MRI remains challenging. Central imaging review is therefore indispensable for clinical trials. Based on the present results, we propose a new, simplified scorecard that will require validation using a similar approach as pursued here. The main challenges are to define measurable versus nonmeasurable (target) lesions and measures of change that allow assessment of response.

Epileptogenic glioblastomas are thought to convey a favorable prognosis, either due to early diagnosis or potential antitumor effects of antiepileptic drugs. We investigated the relationship between survival and epilepsy at presentation, early diagnosis, and antiepileptic drug therapy in glioblastoma patients. Multivariable Cox regression was applied to survival data of 647 consecutive patients diagnosed with de novo glioblastoma between 2005 and 2013 in order to investigate the association between epilepsy and survival in glioblastoma patients. In addition, we quantified the association between survival and valproic acid (VPA) treatment. Epilepsy correlated positively with survival (HR: 0.75 (95% CI: 0.61–0.92), P < .01). This effect is independent of age, sex, performance status, type of surgery, adjuvant therapy, tumor location, and tumor volume, suggesting that this positive correlation cannot be attributed solely to early diagnosis. For patients who presented with epilepsy, the use of the antiepileptic drug VPA did not associate with survival when compared with patients who did not receive VPA treatment. Epilepsy is an independent prognostic factor for longer survival in glioblastoma patients. This prognostic effect is not solely explained by early diagnosis, and survival is not associated with VPA treatment.

We investigated the long-term functional stability and home use of a fully implanted electrocorticography (ECoG)-based brain-computer interface (BCI) for communication by an individual with late-stage Amyotrophic Lateral Sclerosis (ALS). Data recorded from the cortical surface of the motor and prefrontal cortex with an implanted brain-computer interface device was evaluated for 36 months after implantation of the system in an individual with late-stage ALS. In addition, electrode impedance and BCI control accuracy were assessed. Key measures included frequency of use of the system for communication, user and system performance, and electrical signal characteristics. User performance was high consistently over the three years. Power in the high frequency band, used for the control signal, declined slowly in the motor cortex, but control over the signal remained unaffected by time. Impedance increased until month 5, and then remained constant. Frequency of home use increased steadily, indicating adoption of the system by the user. The implanted brain-computer interface proves to be robust in an individual with late-stage ALS, given stable performance and control signal for over 36 months. These findings are relevant for the future of implantable brain-computer interfaces along with other brain-sensing technologies, such as responsive neurostimulation.