Recurrent Glioblastoma-Molecular Underpinnings and Evolving Treatment Paradigms.

Glioblastoma is the most common and lethal central nervous system malignancy with a median survival after progression of only 6-9 months. Major biochemical mechanisms implicated in glioblastoma recurrence include aberrant molecular pathways, a recurrence-inducing tumor microenvironment, and epigenetic modifications. Contemporary standard-of-care (surgery, radiation, chemotherapy, and tumor treating fields) helps to control the primary tumor but rarely prevents relapse. Cytoreductive treatment such as surgery has shown benefits in recurrent glioblastoma; however, its use remains controversial. Several innovative treatments are emerging for recurrent glioblastoma, including checkpoint inhibitors, chimeric antigen receptor T cell therapy, oncolytic virotherapy, nanoparticle delivery, laser interstitial thermal therapy, and photodynamic therapy. This review seeks to provide readers with an overview of (1) recent discoveries in the molecular basis of recurrence; (2) the role of surgery in treating recurrence; and (3) novel treatment paradigms emerging for recurrent glioblastoma.

Single Level Spondylolisthesis Associated Sagittal Plane Imbalance Corrected by Pre-Psoas Interbody Fusion Using Anterior Column Release with 30° Expandable Hyperlordotic Cage.

Background: Loss of lumbar lordosis caused by single level degenerative spondylolisthesis can trigger significant sagittal plane imbalance and failure to correct lumbopelvic parameters during lumbar fusion can lead to poor outcome or worsening deformity. Anterior column release (ACR) through a pre-psoas approach allows the placement of a hyperlordotic cage (HLC) to improve lumbar lordosis, but it is unclear if the amount of cage lordosis affects radiological outcomes in real-life patient conditions. Methods: Three patients were treated with ACR and 30° expandable HLC for positive sagittal imbalance secondary to single-level spondylolisthesis. Patients reported baseline and post-operative Oswestry Disability Index (ODI) and Numeric Pain Score (NRS). Radiographic parameters of sagittal balance included lumbar lordosis (LL), sagittal vertical axis (SVA) and pelvic incidence-lumbar lordosis mismatch (PI-LL). Results: Surgical indications were sagittal plane imbalance caused by L4-L5 degenerative spondylolisthesis (n = 2) and L3-L4 spondylolisthesis secondary to adjacent segmental degeneration (n = 1). Average post-operative length of stay was 3 days (range 2-4) and estimated blood loss was 266 mL (range 200-300). NRS and ODI improved in all patients. All experienced improvements in LL (x¯preop = 33°, x¯postop = 56°), SVA (x¯preop = 180 mm, x¯postop = 61 mm) and PI-LL (x¯preop = 26°, x¯postop = 5°). Conclusion: ACR with expandable HLC can restore sagittal plane balance associated with single-level spondylolisthesis. Failure to perform ACR with HLC placement during pre-psoas interbody fusion may result in under correction of lordosis and poorer outcome for these patients.

Visual system damage and network maladaptation are associated with cognitive performance in neuromyelitis optica spectrum disorders.

Background Neuromyelitis Optica Spectrum Disorders (NMOSD) is an autoimmune disease leading to disability from optic neuritis, myelitis and more rarely brain stem attacks and encephalitis. Patients with NMOSD also exhibit cognitive deficits, the cause of which remains unclear. Recent evidence highlights sensory-cognitive parallel processing converging on the primary visual cortex. The objective of this study was to investigate the effect of the primary visual network disruption from damage caused by optic neuritis on cognition in NMOSD. Methods Twenty-nine aquaporin-4 antibody seropositive patients with NMOSD and 22 healthy controls (HC) completed the brief repeatable battery of neuropsychological tests (BRB-N) and underwent 3 Tesla MRI. Primary visual network functional connectivity (FC) at resting state was analyzed and correlated with performance on BRB-N. These correlations were compared between the groups. Results Patients performed significantly worse than HC on the BRB-N Index score (t = 2.366, p = 0.02). Among HC, visual network FC decreased significantly as cognitive performance on the BRB-N Index score increased (rho(17)=-0.507, p = 0.02). Among patients, this association was absent (rho(23)=0.197, p = 0.18), and the difference in correlation direction and strength to HC was significant (z=-2.175, p = 0.01). Visual network FC was able to explain 19% of the variance in cognitive performance in HC, but none in patients. Conclusions A physiological association of the primary visual network FC and cognitive performance appears absent in patients with NMOSD, suggesting a partial explanation for cognitive deficits. Our findings extend neuroscientific concepts on sensory-cognitive parallel processing neural networks to a clearly defined pathological state, and may be relevant for other diseases with visual system damage.

Insufficient treatment of severe depression in neuromyelitis optica spectrum disorder.

OBJECTIVE: To investigate depression frequency, severity, current treatment, and interactions with somatic symptoms among patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: In this dual-center observational study, we included 71 patients diagnosed with NMOSD according to the International Panel for NMO Diagnosis 2015 criteria. The Beck Depression Inventory (BDI) was classified into severe, moderate, or minimal/no depressive state category. We used the Fatigue Severity Scale to evaluate fatigue. Scores from the Brief Pain Inventory and the PainDETECT Questionnaire were normalized to estimate neuropathic pain. Psychotropic, pain, and immunosuppressant medications were tabulated by established classes. RESULTS: Twenty-eight percent of patients with NMOSD (n = 20) had BDI scores indicative of moderate or severe depression; 48% of patients (n = 34) endorsed significant levels of neuropathic pain. Severity of depression was moderately associated with neuropathic pain (r = 0.341, p < 0.004) but this relationship was confounded by levels of fatigue. Furthermore, only 40% of patients with moderate or severe depressive symptoms received antidepressant medical treatment. Fifty percent of those treated reported persistent moderate to severe depressive symptoms under treatment. CONCLUSIONS: Moderate and severe depression in patients with NMOSD is associated with neuropathic pain and fatigue and is insufficiently treated. These results are consistent across 2 research centers and continents. Future research needs to address how depression can be effectively managed and treated in NMOSD.