Reforming support systems of newly diagnosed brain cancer patients: a systematic review.

PURPOSE: Despite the increasing incidence of currently incurable brain cancer, limited resources are placed in patients' support systems, with reactive utilisation late in the disease course, when physical and psychological symptoms have peaked. Based on patient-derived data and emphasis on service improvement, this review investigated the structure and efficacy of the support methods of newly diagnosed brain cancer patients in healthcare systems. METHODS: This systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. Articles from PubMed, Embase, and CENTRAL databases were screened with six pre-established eligibility criteria, including assessment within 6 months from diagnosis of a primary malignant brain tumour. Risk of bias was evaluated using the Newcastle-Ottawa Scale and Critical Appraisal Skills Program (CASP) Qualitative Studies Checklist. RESULTS: Of 5057 original articles, 14 were eligible for qualitative synthesis. Four studies were cross-sectional and ten were descriptive. Information given to patients was evaluated in seven studies, communication with patients in nine, and patient participation in treatment decisions in eight. Risk of bias was low in ten studies, moderate in two, and high in two. CONCLUSIONS: Techniques promoting individualised care increased perceived support, despite poor patient-physician communication and complexity of the healthcare system. Extracted data across 14 included studies informed a set of guidelines and a four-step framework. These can help evaluate and reform healthcare services to better accommodate the supportive needs of this patient group.

Practical, Stereotactic, Low-Profile Technique for Transcortical/Transventricular Colloid Cyst Removal Independent of Ventricular Size: Technical Note and Analysis of Approaches.

BACKGROUND: In the presence of a dilated foramen of Monro, a transcortical, transforaminal approach is considered the safest and simplest approach for resection of colloid cysts. However, in the presence of small or normal frontal horns, numerous microsurgical approaches and, often complicated, variations have been described, invariably employing forms of stereotactic navigation. OBJECTIVE: To report an alternative, accurate, microsurgical stereotactic low-profile technique. METHODS: The small frontal horn is stereotactically targeted as previously described. Routine equipment is used to accurately create a novel, rigid, atraumatic surgical corridor. RESULTS: After a 7-mm corticotomy, a peel-away catheter carrying the AxiEM stylet engages the target set as the frontal horn. All joints of the endoscope holder are locked, allowing only catheter advancement (y axis) while lateral (x axis) or anteroposterior (z axis) movements are secure. Two, 7-mm retractor blades are inserted. The extremely consistent anatomy of the foramen of Monro allows en bloc microsurgical removal without unnecessary coagulation of cyst wall or choroid plexus. CONCLUSION: Despite a plethora of approaches to the rostral third ventricle, in the presence of normal or small frontal horns, including creation of transcallosal/interforniceal, suprachoroidal (or transchoroidal), and sub-choroidal, colloid cyst resection does not necessarily need to be convoluted. Technical nuances of an accurate, practical, minimally invasive technique are described.

Handling Severe Intraoperative Hemorrhage and Avoiding Iatrogenic Stroke During Brain Tumor Surgery: Techniques for Prevention of Hemorrhagic and Ischemic Complications.

BACKGROUND: Nationwide databases show that iatrogenic stroke and postoperative hematoma are among the commonest complications in brain tumor surgery, with a 10-year incidence of 16.3/1000 and 10.3/1000, respectively. However, techniques for handling severe intraoperative hemorrhage and dissecting, preserving, or selectively obliterating vessels traversing the tumor are sparse in the literature. METHODS: Records of the senior author's intraoperative techniques during severe haemorrhage and vessel preservation were reviewed and analyzed. Intraoperative media demonstrations of key techniques were collected and edited. In parallel, a literature search investigating technique description in handling severe intraoperative hemorrhage and vessel preservation in tumor surgery was undertaken. Histologic, anesthetic, and pharmacologic prerequisites of significant hemorrhagic complications and hemostasis were analyzed. RESULTS: The senior author's techniques for arterial and venous skeletonization, temporary clipping with cognitive or motor mapping, and ION monitoring were categorized. Vessels interfacing with tumor are labeled intraoperatively as supplying/draining the tumor, or traversing en passant, while supplying/draining functional neural tissue. Intraoperative techniques of differentiation were analyzed and illustrated. Literature search found 2 vascular-related complication domains in tumor surgery: perioperative management of excessively vascular intraparenchymal tumors and lack of intraoperative techniques and decision processes for dissecting and preserving vessels interfacing or traversing tumors. CONCLUSIONS: Literature searches showed a dearth of complication-avoidance techniques in tumor-related iatrogenic stroke, despite its high prevalence. A detailed preoperative and intraoperative decision process was provided along with a series of case illustrations and intraoperative videos showing the techniques required to reduce intraoperative stroke and associated morbidity addressing a void in complication avoidance of tumor surgery.

Intraoperative stimulation mapping of thalamocortical tracts in asleep and awake settings: novel electrophysiological, anatomical, and tractographic paradigms.

OBJECTIVE: Despite the disabling deficits of motor apraxia and sensory ataxia resulting from intraoperative injury of the superior thalamocortical tracts (TCTs), region-specific electrophysiological localization is currently lacking. Herein, the authors describe a novel TCT mapping paradigm. METHODS: Three patients, 1 asleep and 2 awake, underwent glioma resection affecting primarily the somatosensory cortex and underlying TCT. Stimulation was performed at the median, ulnar, and posterior tibial nerves. Parameters comprised single anodal pulses (duration 200-500 µsec, 2.1-4.7 Hz) with a current ranging from 10 to 25 mA. Recordings were captured with a bipolar stimulation probe, avoiding the classic collision technique. Positive localization sites were used to tractographically reconstruct the TCT in the third case. RESULTS: Employing one electrophysiological paradigm, the TCT was localized subcortically in all 3 cases by using a bipolar probe, peak range of 19.6-29.2 msec, trough of 23.3-34.8 msec, stimulation range of 10-25 mA. In the last case, tractographic reconstruction of the TCT validated a highly accurate TCT localization within a specific region of the posterior limb of the internal capsule. CONCLUSIONS: The authors describe the first electrophysiological technique for intraoperative localization and protection of the TCT in both asleep and awake craniotomies with tractographic validation, while avoiding the collision paradigm. None of the above paradigms have been previously reported. More data are required to further validate this technique.

Discriminators of pseudoprogression and true progression in high-grade gliomas: A systematic review and meta-analysis.

High-grade gliomas remain the most common primary brain tumour with limited treatments options and early recurrence rates following adjuvant treatments. However, differentiating true tumour progression (TTP) from treatment-related effects or pseudoprogression (PsP), may critically influence subsequent management options. Structural MRI is routinely employed to evaluate treatment responses, but misdiagnosis of TTP or PsP may lead to continuation of ineffective or premature cessation of effective treatments, respectively. A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses method. Embase, MEDLINE, Web of Science and Google Scholar were searched for methods applied to differentiate PsP and TTP, and studies were selected using pre-specified eligibility criteria. The sensitivity and specificity of included studies were summarised. Three of the identified methods were compared in a separate subgroup meta-analysis. Thirty studies assessing seven distinct neuroimaging methods in 1372 patients were included in the systematic review. The highest performing methods in the subgroup analysis were DWI (AUC = 0.93 [0.91-0.95]) and DSC-MRI (AUC = 0.93 [0.90-0.95]), compared to DCE-MRI (AUC = 0.90 [0.87-0.93]). 18F-fluoroethyltyrosine PET (18F-FET PET) and amide proton transfer-weighted MRI (APTw-MRI) also showed high diagnostic accuracy, but results were based on few low-powered studies. Both DWI and DSC-MRI performed with high sensitivity and specificity for differentiating PsP from TTP. Considering the technical parameters and feasibility of each identified method, the authors suggested that, at present, DSC-MRI technique holds the most clinical potential.

Converting sounds to meaning with ventral semantic language networks: integration of interdisciplinary data on brain connectivity, direct electrical stimulation and clinical disconnection syndromes.

Numerous traditional linguistic theories propose that semantic language pathways convert sounds to meaningful concepts, generating interpretations ranging from simple object descriptions to communicating complex, analytical thinking. Although the dual-stream model of Hickok and Poeppel is widely employed, proposing a dorsal stream, mapping speech sounds to articulatory/phonological networks, and a ventral stream, mapping speech sounds to semantic representations, other language models have been proposed. Indeed, despite seemingly congruent models of semantic language pathways, research outputs from varied specialisms contain only partially congruent data, secondary to the diversity of applied disciplines, ranging from fibre dissection, tract tracing, and functional neuroimaging to neuropsychiatry, stroke neurology, and intraoperative direct electrical stimulation. The current review presents a comprehensive, interdisciplinary synthesis of the ventral, semantic connectivity pathways consisting of the uncinate, middle longitudinal, inferior longitudinal, and inferior fronto-occipital fasciculi, with special reference to areas of controversies or consensus. This is achieved by describing, for each tract, historical concept evolution, terminations, lateralisation, and segmentation models. Clinical implications are presented in three forms: (a) functional considerations derived from normal subject investigations, (b) outputs of direct electrical stimulation during awake brain surgery, and (c) results of disconnection syndromes following disease-related lesioning. The current review unifies interpretation of related specialisms and serves as a framework/thinking model for additional research on language data acquisition and integration.

Resection of Ependymomas Infiltrating the Fourth Ventricular Floor: Anatomosurgical and Stimulation Mapping Techniques.

BACKGROUND: Despite the importance of complete, gross total resection (GTR) of fourth ventricular ependymomas, significant morbidity and/or subtotal resections are reported, particularly when the ventricular floor is infiltrated. Step-by-step technique descriptions are lacking in the literature. OBJECTIVE: To describe monitoring and stimulation mapping techniques and surgical nuances in the challenging subgroup of infiltrating fourth ventricular ependymomas by a highly illustrated, step-by-step description. Superimposed outlines of cranial nerve nuclei on the surgical field demonstrate critical anatomy and facilitate understanding in a way not previously presented. METHODS: We reviewed the microanatomical and neurophysiological prerequisites of resecting a diffusively infiltrating fourth ventricular ependymoma. RESULTS: We achieved GTR with the use of reproducible stimulating mapping and accurate cranial nerve nuclei identification. CONCLUSION: Enhanced microanatomical understanding, reproducible stimulation mapping, and meticulous resection techniques can result in GTR, even in diffusively infiltrating ependymomas.

Genetic alterations in non-syndromic, familial gliomas in first degree relatives: A systematic review.

OBJECTIVE: Despite numerous reports in syndromic gliomas, the underlying genetic and molecular basis of familial, non-syndromic gliomas, in first degree relatives, remains unclear. This rare cohort of patients harboring invasive primary brain tumors with poor prognosis may provide a potential substrate of understanding the complex genetic cascade triggering tumorigenesis. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) 2015 and The Cochrane Handbook of Systematic Reviews of Interventions. PubMed/MEDLINE, Embase and CENTRAL databases were accessed with set inclusion and exclusion criteria. RESULTS: Following returns of 6756 articles, systematic analysis resulted in 48 papers, with 18 case series, 4 linkage analysis, 3 case-control studies, 1 cohort study, and 22 case reports. A total of 164 first degree relatives of 72 families were analyzed. The most common genetic alterations associated with non-syndromic familial gliomas reported to affect chromosomes 17 (51.1 % germline and 9.3 % tumor mutations), 22 (15.6 % germline and 6 % tumor mutations) and 1 and 19 (4.4 % germline and 9.3 % tumor mutations), with the most commonly affected genes TP53 (8.5 %) and NF2 (3.7 %). Tumor suppressors or cell-cycle regulators, cell signaling and transcription regulation or methylation were the most common gene function categories. CONCLUSION: Four specific chromosomes (17, 22, 1 and 19) and two specific genes (TP53 and NF2) appear to be most commonly involved. This appears to be the first systematic review of genetic factors underlying non-syndromic glioma clustering in families. The defined list of genetic abnormalities, linked to familial gliomas, may facilitate therapeutic targets and future treatment design.

High Interrater Variability in Intraoperative Language Testing and Interpretation in Awake Brain Mapping Among Neurosurgeons or Neuropsychologists: An Emerging Need for Standardization.

OBJECTIVE: Brain mapping with direct electric stimulation is considered the gold standard for maximum safe resection of tumors affecting eloquent regions. However, no consensus exists in selection and interpretation of intraoperative testing for language and other cognitive domains. Our aim was to capture and statistically analyze variability in practices in intraoperative language testing among neurosurgeons and neuropsychologists in the United States, Europe, and the rest of the world. METHODS: An electronic questionnaire was developed by a multidisciplinary team at Queen Square, London, and distributed internationally through selected organized societies. The survey included 2 domains: terminology and common understanding of clinical deficits; and selection of intraoperative tests used per specific brain region. Participants were stratified by specialty, years of experience, and monthly caseload. Data were analyzed using Krippendorff α, Wilcoxon rank sum test, and Kruskal-Wallis analysis of variance. RESULTS: A total of 137 specialists participated. A low agreement was recorded for each of the 20 questions (Krippendorff α = -0.023 to 0.312). Further subgroup analysis revealed low interrater reliability independent of specialism (neurosurgeons, α = 0.013-0.318 compared with nonneurosurgeons, α = -0.021 to 0.398; P = 0.808) and years of experience (<1 years, α = -0.003 to 0.282; 2-5 years, α = 0.009-0.327; 6-10 years, α = 0.003-0.234; and >10 years, α = -0.003 to 0.372; P = 0.200). CONCLUSIONS: The current study documents high interrater variability, regardless of specialism and years of experience in the cohort of neurosurgeons and language specialists surveyed and may be applicable to a wider group of specialists, indicating the need to reduce interobserver, interinstitutional and interspecialty variability, reach consensus, and increase the validity, interpretation, and predictive power of intraoperative mapping.