The surgical treatment of insular gliomas requires specialized knowledge. Over the last three decades, increased momentum in surgical resection of insular gliomas shifted the focus from one of expectant management to maximal safe resection to establish a diagnosis, characterize tumor genetics, treat preoperative symptoms (i.e., seizures), and delay malignant transformation through tumor cytoreduction. A comprehensive review of the literature was performed regarding insular glioma classification/genetics, insular anatomy, surgical approaches, and patient outcomes. Modern large, published series of insular resections have reported a median 80% resection, 80% improvement in preoperative seizures, and postsurgical permanent neurologic deficits of less than 10%. Major complication avoidance includes recognition and preservation of eloquent cortex for language and respecting the lateral lenticulostriate arteries.

Frontotemporal dementia (FTD) is a devastating neurodegenerative condition for which there is currently no effective treatment. Although it is much less common than Alzheimer’s disease, the impact of FTD is increased by its relatively early onset and high heritability. Clinical heterogeneity and overlap with other neurodegenerative and psychiatric syndromes complicate diagnosis. However, recent advances in our understanding of the molecular basis of FTD provide a foundation for the development of much-needed biomarkers and targeted therapies. This review provides a summary of the recently revised clinical criteria for FTD, highlights diagnostic challenges, briefly summarizes recent molecular discoveries and then focuses on promising developments in biomarkers and clinical trials.

Background: Variants in CLCN4 are implicated in neurodevelopmental disorder, X-linked intellectual disability, and epileptic encephalopathy. CLCN4 encodes ClC-4, which is hypothesized to play a role in ion homeostasis and intracellular trafficking. ClC-4 relies on its formation of heterodimers with ClC-3, which possesses signals for target organelles. Methods: Case-Series. Then, we performed heterologous expression, patch-clamp electrophysiology, confocal microscopy, and protein biochemistry experiments to characterize our patients’ ClC-4 variants. Results: All three male patients had developmental and epileptic encephalopathy. Patients #1 and #2 had normal-appearing brains on MRI and no dysmorphic features. Patient #3 had: microcephaly, microsomia, complete agenesis of the corpus-callosum; and, cerebellar and brainstem hypoplasia. Patient #1 had recurrent status epilepticus separated by months of seizure freedom, while Patient #2 and #3 had brief, daily seizures. The p.Gly342Arg variant impaired the heterodimerization capability of ClC-4. The p.Ile549Leu and p.Asp89Asn variants exhibited early transport-activation, with p.Asp89Asn favouring higher transport-activity of ClC-4. Conclusions: We extend the phenotypic spectrum of CLCN4 variants and demonstrate the pathological functional-consequences of three previously unclassified variants. The p.Gly342Arg variant lead to a loss-of-function phenotype; however, the p.Ile549Leu and p.Asp89Asn variants likely caused gain-of-function phenotypes. Targeted animal or induced pluripotent stem-cell models are needed to further understand epileptogenic mechanisms of CLCN4 variants.

The complement system is a tightly controlled signaling network that plays a role in innate immune surveillance. However, abnormal signaling through this pathway contributes to tissue damage in several inflammatory, autoimmune, and degenerative diseases. Myasthenia gravis (MG) and neuromyelitis optica spectrum disorders (NMOSD) have complement dysfunction at the core of pathogenesis, providing a strong rationale for therapeutic targeting of complement components. The purpose of this paper is to briefly review the role of complement activation in the pathogenesis of MG and NMOSD, to discuss the rationale and evidence for complement inhibition as a method to manage these diseases, and to provide a Canadian perspective on the use of complement inhibition therapy through real-world cases of MG and NMOSD.

Rapid advances in neurotechnology and neurosurgery are positioned to revolutionize care for patients suffering from debilitating neurological and psychiatric disease. Enthusiasm for the adoption of these technologies is tempered by ethical dilemmas regarding resource allocation, provision of care, communication with patients and other providers, and other potential pitfalls. In the present work, we discuss bioethical implications of novel neurotechnologies for medical practice. In particular, we examine the implications of neurotechnological advancement through the lens of professional communication. Emerging challenges within this domain are presented in the context of physician interactions with four key partners: (i) patients; (ii) other physicians; (iii) industry; and (iv) society-at-large. Anticipated issues as well as mitigation strategies are discussed as they relate to communication with these stakeholders.

Background: The late-onset cerebellar ataxias (LOCAs) have until recently resisted molecular diagnosis. Contributing to this diagnostic gap is that non-coding structural variations, such as repeat expansions, are not fully accessible to standard short-read sequencing analysis. Methods: We combined bioinformatics analysis of whole-genome sequencing and long-read sequencing to search for repeat expansions in patients with LOCA. We enrolled 66 French-Canadian, 228 German, 20 Australian and 31 Indian patients. Pathogenic mechanisms were studied in post-mortem cerebellum and induced pluripotent stem cell (iPSC)-derived motor neurons from 2 patients. Results: We identified 128 patients who carried an autosomal dominant GAA repeat expansion in the first intron of the FGF14 gene. The expansion was present in 61%, 18%, 15% and 10% of patients in the French-Canadian, German, Australian and Indian cohorts, respectively. The pathogenic threshold was determined to be (GAA)≥250, although incomplete penetrance was observed in the (GAA)250-300 range. Patients developed a slowly progressive cerebellar syndrome at an average age of 59 years. Patient-derived post-mortem cerebellum and induced motor neurons both showed reduction in FGF14 RNA and protein expression compared to controls. Conclusions: This intronic, dominantly inherited GAA repeat expansion in FGF14 represents one of the most common genetic causes of LOCA uncovered to date.