Hemifacial Spasm and Neurovascular Compression

Hemifacial spasm (HFS) is characterized by involuntary unilateral contractions of the muscles innervated by the ipsilateral facial nerve, usually starting around the eyes before progressing inferiorly to the cheek, mouth, and neck. Its prevalence is 9.8 per 100,000 persons with an average age of onset of 44 years. The accepted pathophysiology of HFS suggests that it is a disease process of the nerve root entry zone of the facial nerve. HFS can be divided into two types: primary and secondary. Primary HFS is triggered by vascular compression whereas secondary HFS comprises all other causes of facial nerve damage. Clinical examination and imaging modalities such as electromyography (EMG) and magnetic resonance imaging (MRI) are useful to differentiate HFS from other facial movement disorders and for intraoperative planning. The standard medical management for HFS is botulinum neurotoxin (BoNT) injections, which provides low-risk but limited symptomatic relief. The only curative treatment for HFS is microvascular decompression (MVD), a surgical intervention that provides lasting symptomatic relief by reducing compression of the facial nerve root. With a low rate of complications such as hearing loss, MVD remains the treatment of choice for HFS patients as intraoperative technique and monitoring continue to improve

Surgical treatment of symptomatic pineal cysts without hydrocephalus-meta-analysis of the published literature

Background To examine published data and assess evidence relating to safety and efficacy of surgical management of symptomatic pineal cysts without hydrocephalus (nhSPC), we performed a systematic review of the literature and meta-analysis. Methods Following the PRISMA guidelines, we searched Pubmed and SCOPUS for all reports with the query 'Pineal Cyst' AND 'Surgery' as of March 2021, without constraints on study design, publication year or status (PROSPERO_CRD:42,021,242,517). Assessment of 1537 hits identified 26 reports that met inclusion and exclusion criteria. Results All 26 input studies were either case reports or single-centre retrospective cohorts. The majority of outcome data were derived from routine physician-recorded notes. A total of 294 patients with surgically managed nhSPC were identified. Demographics: Mean age was 29 (range: 4-63) with 77% females. Mean cyst size was 15 mm (5-35). Supracerebellar-infratentorial approach was adopted in 90% of cases, occipital-transtentorial in 9%, and was not reported in 1%. Most patients were managed by cyst resection (96%), and the remainder by fenestration. Mean post-operative follow-up was 35 months (0-228). Presentation: Headache was the commonest symptom (87%), followed by visual (54%), nausea/vomit (34%) and vertigo/dizziness (31%). Other symptoms included focal neurology (25%), sleep disturbance (17%), cognitive impairment (16%), loss of consciousness (11%), gait disturbance (11%), fatigue (10%), 'psychiatric' (2%) and seizures (1%). Mean number of symptoms reported at presentation was 3 (0-9). Outcomes: Improvement rate was 93% (to minimise reporting bias only consecutive cases from cohort studies were considered, N= 280) and was independent of presentation. Predictors of better outcomes were large cyst size (OR= 5.76; 95% CI: 1.74-19.02) and resection over fenestration (OR= 12.64; 3.07-52.01). Age predicted worse outcomes (OR= 0.95; 0.91-0.99). Overall complication rate was 17% and this was independent of any patient characteristics. Complications with long-term consequences occurred in 10 cases (3.6%): visual disturbance (3), chronic incisional pain (2), sensory disturbance (1), fatigue (1), cervicalgia (1), cerebellar stroke (1) and mortality due to myocardial infarction (1). Conclusions Although the results support the role of surgery in the management of nhSPCs, they have to be interpreted with a great deal of caution as the current evidence is limited, consisting only of case reports and retrospective surgical series. Inherent to such studies are inhomogeneity and incompleteness of data, selection bias and bias related to assessment of outcome carried out by the treating surgeon in the majority of cases. Prospective studies with patient-reported and objective outcome assessment are needed to provide higher level of evidence.Peer reviewe

LOH in the HLA Class I Region at 6p21 Is Associated with Shorter Survival in Newly Diagnosed Adult Glioblastoma

PurposeGlioblastoma (GBM) shows downregulated expression of human leukocyte antigen (HLA) class I, thereby escaping from cytotoxic T cells and limiting the efficacy of immunotherapy. Loss of heterozygosity (LOH) of HLA class I (6p21) and/or β-2 microglobulin (B2m) (15q21) regions represents irreversible downregulation. In this study, we examined the prevalence of these LOH events and their relations with overall survival in GBM.Experimental designIn a cross-sectional analysis on 60 adult patients with GBM, DNA from formalin-fixed, paraffin-embedded specimens were evaluated for 10 microsatellite regions of HLA class I, B2m, HLA class II, HLA class III, and 6q by PCR as well as immunohistochemical evaluation of HLA class I expression and CD8(+) T-cell infiltration.ResultsLOH in HLA class I, B2m, HLA class II, HLA class III, and 6q regions was present in 41.4%, 18.2%, 9.4%, 77.8%, and 36.0% of informative cases, respectively. LOH of HLA class I was associated with shorter overall survival (HR = 4.89, P = 0.0078). HLA class I was downregulated in 22% to 43% of cases based on immunohistochemistry. Cases that displayed negative staining were significantly younger. HLA class I expression correlated with intratumoral CD8(+) T-cell infiltration.ConclusionLOH in the HLA class I region is frequent in adult GBMs. The association of shorter survival with LOH in this region suggests a crucial role for these genes in immunosurveillance

Connectivity model of the anatomic substrates and network abnormalities in major depressive disorder: A coordinate meta-analysis of resting-state functional connectivity

Increasing data suggests major depressive disorder (MDD) involves abnormal functional connectivity within a variety of large-scale brain networks. However, due to the use of unstandardized parcellation schemes, the interactions between these networks and the specific neuroanatomic substrates involved requires further review. We therefore sought to conduct a meta-analysis of functional connectivity changes encountered in MDD using a detailed and standardized parcellation scheme. A literature search for relevant resting-state fMRI studies related to MDD in PubMed was conducted. BrainMap's GingerALE 2.3.6 extracted the relevant fMRI data for creation of an activation likelihood estimation (ALE). A sphere was placed at the MNI coordinate of each ALE cluster and seed origin point, and the Human Connectome Project (HCP) parcellation schema was projected on these spheres. The parcellations most present in the ALE were analyzed based on their associated functional network and/or subcortical area to identify abnormal pairs based on the ALE and seed origin parcellation. Ultimately, 483 subjects across 15 studies were analyzed, wherein areas of decreased or increased functional connectivity compared to healthy controls were identified. Our MDD model most commonly implicated increased default mode network (DMN)-central executive network (CEN) pairs, while decreased paired networks commonly included the DMN with other brain networks. All intra DMN-DMN connections and salience network (SN) pairs showed decreased functional connectivity, while all intra CENCEN functional connectivity were increased compared to controls. We hypothesize that our findings of abnormal connectivity between the DMN, CEN, and SN core cognitive networks may demonstrate the inappropriate allocation of cognitive resources and cognitive depletion believed to cause persisting rumination in depression. Despite previous claims, DMN connectivity was found to be generally decreased, and we propose its connectivity direction is dependent on its interacting network partner and the specific parcellations involved. While both of these hypotheses remain speculative and require further validation, our work provides a  comprehensive and anatomically precise model to be refined in future studies focusing on the functional connectivity underlying MDD pathophysiology

Topology of the lateral visual system: The fundus of the superior temporal sulcus and parietal area H connect nonvisual cerebrum to the lateral occipital lobe

Abstract Background and Purpose Mapping the topology of the visual system is critical for understanding how complex cognitive processes like reading can occur. We aim to describe the connectivity of the visual system to understand how the cerebrum accesses visual information in the lateral occipital lobe. Methods Using meta‐analytic software focused on task‐based functional MRI studies, an activation likelihood estimation (ALE) of the visual network was created. Regions of interest corresponding to the cortical parcellation scheme previously published under the Human Connectome Project were co‐registered onto the ALE to identify the hub‐like regions of the visual network. Diffusion Spectrum Imaging‐based fiber tractography was performed to determine the structural connectivity of these regions with extraoccipital cortices. Results The fundus of the superior temporal sulcus (FST) and parietal area H (PH) were identified as hub‐like regions for the visual network. FST and PH demonstrated several areas of coactivation beyond the occipital lobe and visual network. Furthermore, these parcellations were highly interconnected with other cortical regions throughout extraoccipital cortices related to their nonvisual functional roles. A cortical model demonstrating connections to these hub‐like areas was created. Conclusions FST and PH are two hub‐like areas that demonstrate extensive functional coactivation and structural connections to nonvisual cerebrum. Their structural interconnectedness with language cortices along with the abnormal activation of areas commonly located in the temporo‐occipital region in dyslexic individuals suggests possible important roles of FST and PH in the integration of information related to language and reading. Future studies should refine our model by examining the functional roles of these hub areas and their clinical significance

LOH in the HLA Class I Region at 6p21 Is Associated with Shorter Survival in Newly Diagnosed Adult Glioblastoma

PURPOSE: Glioblastoma (GBM) demonstrate down-regulated expression of Human Leukocyte Antigen (HLA) Class I, thereby escaping from cytotoxic T cells and limiting the efficacy of immunotherapy. LOH of HLA Class I (6p21) and/or Beta-2 microglobulin (B2m) (15q21) regions represent irreversible down-regulation. In this study, we examined the prevalence of these LOH events and their relations with overall survival in GBM. EXPERIMENTAL DESIGN: In a cross-sectional analysis on 60 adult GBM patients, DNA from formalin-fixed paraffin-embedded specimens were evaluated for ten microsatellite regions of HLA Class I, B2m, HLA Class II, HLA Class III, and 6q by PCR as well as immunohistochemical evaluation of HLA Class I expression and CD8(+) T cell infiltration. RESULTS: LOH in HLA Class I, B2m, HLA Class II, HLA Class III, and 6q regions were present in 41.4%, 18.2%, 9.4%, 77.8%, and 36.0% of informative cases, respectively. LOH of HLA Class I was associated with shorter overall survival (HR = 4.89, p = 0.0078). HLA Class I was down-regulated in 22 to 43% of cases based on immunohistochemistry. Cases that displayed negative staining were significantly younger. HLA Class I expression correlated with intratumoral CD8(+) T cell infiltration. CONCLUSION: LOH in the HLA Class I region is frequent in adult GBMs. The association of shorter survival with LOH in this region suggest a crucial role for these genes in immunosurveillance

Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy

Despite surgery and radiotherapy, as many as 50 % of children with ependymomas will suffer from tumor recurrences that will ultimately lead to death. Our group’s initial peptide-based glioma vaccine targeting EphA2, IL-13Rα2, and Survivin, which are overexpressed in pediatric gliomas, has shown promise in its initial phase of testing. We therefore investigated whether EphA2, IL-13Raα2, Survivin, and, additionally, Wilms’ Tumor 1 (WT1), are overexpressed in pediatric ependymomas to determine if a similar immunotherapy approach could be applicable. Immunohistochemistry was performed using antibodies specific for EphA2, IL-13Rα2, Survivin, and WT1 on paraffin-embedded specimens from 19 pediatric and 13 adult ependymomas. Normal brain and ependyma were used for background staining controls. Negative staining was defined as no staining or staining equaling the background intensity in normal brain tissues. In the 19 pediatric cases, 18 (95 %) demonstrated positive staining for EphA2, 16 (84 %) for IL-13Rα2, 18 (95 %) for Survivin, and only 7 (37 %) for WT1. Only 3 of 19 cases were positive for two or fewer tumor-associated antigens (TAAs); 16 of 19 cases were positive for three or more TAAs. In the 13 adult cases, all 13 demonstrated positive staining for EphA2, IL-13Rα2, and Survivin. Only 2 of 13 cases (15 %) demonstrated positive staining for WT1. All adult specimens were positive for three or more TAAs. Some ependymomas showed patchy variability in intensity. Pediatric and adult ependymomas frequently express EphA2, IL-13Rα2, and Survivin. This provides the basis for the utilization of an established multiple peptide vaccine for ependymoma in a clinical trial setting