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Background Proximal junctional kyphosis is a kyphotic deformity following spine instrumentation, predominantly seen in scoliosis patients. There have been previous attempts to develop classification schema of PJK. We analyzed the factors contributing to PJK based upon our own clinical experience with the goal of developing a clinical guidance tool which took into account both etiology and mechanism of failure. Methods: We performed a retrospective analysis of all re-operation thoracolumbar surgeries at a single institution over a 14-year period. Patients with PJK were identified and categorized based upon the etiology, mechanism of failure, and an indication of revision. Next, we conducted a systematic review on articles emphasizing a classification system for PJK. Results: Fourteen PJK patients were identified out of 121 patients who required revision spine surgery. The average age was 64.9 ± 10.2 years, with 10 males (71%) and 4 females (29%). Three primary etiologies were identified: 6/14 (47%) overcorrection, 6/14 (47%) osteopenia, and 2/14 (14%) ligamentous disruption. The mechanism of failure was likewise divided into three categories: 9/14 (64%) compression fracture, 1/14 (7%) hardware failure, and 4/14 (29%) disc degeneration. The relationship between osteopenia and the development of a compression fracture leading to PJK was statistically significant (p = 0.031). Conclusion: There are multiple current classification systems for PJK. Our study findings were in line with previously published literature and suggest the need for a future classification system combining both etiology, mechanism of failure, and severity of disease.

Laser interstitial thermal therapy is a minimally invasive surgical alternative to craniotomy that uses laser light through a fiber optic probe placed within a target lesion to create thermal tissue damage, resulting in cellular death. It is used in neuro-oncology to treat inaccessible lesions and obviate morbidity in high-risk patients. Overall complication rates and outcome measures are comparable with those seen in radiation and/or craniotomy. Laser interstitial thermal therapy can be an effective option for recurrent brain metastases. Prospective, randomized trials must be performed to evaluate the efficacy of laser interstitial thermal therapy as a primary treatment for brain metastases.

Patients who present with traumatic brain injury (TBI) combined with blunt cerebrovascular injuries (BCVI) are difficult to manage, in part because treatment for each entity may exacerbate the other. It is necessary to develop a treatment paradigm that ensures maximum benefit while mitigating the opposing risks. A cohort of 150 patients from 2015 to present, with either internal carotid artery (ICA) and/or vertebral artery (VA) dissections or pseudoaneurysms, was cross-referenced with those who had sustained TBI. Of the 38 patients identified with both TBI and BCVI, 25 suffered ICA injuries, 10 had VA injuries and 3 had combined ICA/VA injuries. Unilateral BCVI occurred in 30 patients, while 8 had bilateral BCVI. Two patients required surgical intervention for TBI, and 5 patients required endovascular intervention for BCVI. Positive emboli detection studies (EDS) on transcranial dopplers (TCD) were demonstrated in 19 patients, with 9 patients having radiographic evidence of stroke. Anti-platelet therapy was initiated in 32 patients, and anti-coagulation in 10 patients, without new or worsening intracranial hemorrhages (ICH). Overall, 76% of patients were able to be discharged home or to rehabilitation, with good recovery demonstrated in 73% of the patients who had appropriate follow-up. In the setting of concurrent TBI and BCVI, use of anti-platelet/coagulation to prevent stroke can be safe if monitored closely. Here we describe a treatment paradigm which weighs the risk and benefits of therapies based on severity of ICH and stroke prevention, which tended to result in good disposition and recovery.

Summary: Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis. : In a human neural stem cell model of low-grade astrocytoma, Modrek et al. show that mutant IDH1 and loss of P53 and ATRX together block differentiation via disassociation of SOX2 from putative enhancers. This occurs because of disruption of chromatin looping secondary to hypermethylation at CTCF motifs. Keywords: low-grade glioma, astrocytoma, IDH, P53, ATRX, neural stem cells, SOX2, chromatin looping, CTCF, DNA methylation

Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

The (CGG)n-repeat in the 5′-untranslated region of the fragile X mental retardation gene ( FMR1) gene is polymorphic and may become unstable on transmission to the next generation. In fragile X syndrome, CGG repeat lengths exceed 200, resulting in silencing of FMR1 and absence of its protein product, fragile X mental retardation protein (FMRP). CGG repeat lengths between 55 and 200 occur in fragile X premutation (FXPM) carriers and have a high risk of expansion to a full mutation on maternal transmission. FXPM carriers have an increased risk for developing progressive neurodegenerative syndromes and neuropsychological symptoms. FMR1 mRNA levels are elevated in FXPM, and it is thought that clinical symptoms might be caused by a toxic gain of function due to elevated FMR1 mRNA. Paradoxically, FMRP levels decrease moderately with increasing CGG repeat length in FXPM. Lowered FMRP levels may also contribute to the appearance of clinical problems. We previously reported increases in regional rates of cerebral protein synthesis (rCPS) in the absence of FMRP in an Fmr1 knockout mouse model and in a FXPM knockin (KI) mouse model with 120 to 140 CGG repeats in which FMRP levels are profoundly reduced (80%–90%). To explore whether the concentration of FMRP contributes to the rCPS changes, we measured rCPS in another FXPM KI model with a similar CGG repeat length and a 50% reduction in FMRP. In all 24 brain regions examined, rCPS were unaffected. These results suggest that even with 50% reductions in FMRP, normal protein synthesis rates are maintained.