Intraventricular Glioma in Pediatric Patients: A Systematic Review of Demographics, Clinical Characteristics, and Outcomes.

OBJECTIVE: We conducted a systematic review on pediatric intraventricular gliomas to survey the patient population, tumor characteristics, management, and outcomes. METHODS: PubMed, Scopus, Web-of-Science, and Cochrane were searched using PRISMA guidelines to include studies reporting pediatric patients with intraventricular gliomas. RESULTS: A total of 30 studies with 317 patients were included. Most patients were male (54%), diagnosed at a mean age of 8 years (0.2-19), and frequently exhibited headache (24%), nausea and vomiting (21%), and seizures (15%). Tumors were predominantly located in the fourth (48%) or lateral ventricle (44%). Most tumors were WHO grade 1 (68%). Glioblastomas were rarely reported (2%). Management included surgical resection (97%) radiotherapy (27%), chemotherapy (8%), and cerebrospinal fluid diversion for hydrocephalus (38%). Gross total resection was achieved in 59% of cases. Cranial nerve deficit was the most common post-surgical complication (28%) but most were reported in articles published prior to the year 2000 (89%). Newer cases published during or after the year 2000 exhibited significantly higher rates of gross total resection (78% vs. 39%, p<0.01), lower rates of recurrence (26% vs. 47%, p<0.01), longer average overall survival time (42 vs 21 months, p=0.02), and a higher proportion of patients alive (83% vs. 70%, p=0.03) than older cases. CONCLUSIONS: Pediatric intraventricular gliomas correlate with parenchymal pediatric gliomas in terms of age at diagnosis and general outcomes. The mainstay of management is complete surgical excision and more recent studies report longer overall survival rates and less cranial nerve complications.

HMGB1 mediates microbiome-immune axis dysregulation underlying reduced neutralization capacity in obesity-related post-acute sequelae of SARS-CoV-2.

While obesity is a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC, "long-COVID"), the mechanism(s) underlying this phenomenon remains poorly understood. To address this gap in knowledge, we performed a 6-week longitudinal study to examine immune activity and gut microbiome dysbiosis in post-acute stage patients recovering from SARS-CoV-2 infection. Self-reported symptom frequencies and blood samples were collected weekly, with plasma assessed by ELISA and Luminex for multiple biomarkers and immune cell profiling. DNA from stool samples were collected at the early stage of recovery for baseline assessments of gut microbial composition and diversity using 16S-based metagenomic sequencing. Multiple regression analyses revealed obesity-related PASC linked to a sustained proinflammatory immune profile and reduced adaptive immunity, corresponding with reduced gut microbial diversity. In particular, enhanced signaling of the high mobility group box 1 (HMGB1) protein was found to associate with this dysregulation, with its upregulated levels in plasma associated with significantly impaired viral neutralization that was exacerbated with obesity. These findings implicate HMGB1 as a candidate biomarker of PASC, with potential applications for risk assessment and targeted therapies.

Middle meningeal artery embolization for symptomatic chronic subdural hematoma in the setting of severe transfusion-refractory thrombocytopenia: A case study and review of literature.

Background: Surgical decompression for the treatment of chronic subdural hematomas (cSDHs) is irrefutably effective; however, its utility in managing cSDH in patients with comorbid coagulopathy remains controversial. The optimal threshold for platelet transfusion in cSDH management is <100,000/mm3, according to guidelines from the American Association of Blood Banks GRADE framework. This threshold may be unachievable in refractory thrombocytopenia, though surgical intervention may still be warranted. We present a patient with symptomatic cSDH and transfusion-refractory thrombocytopenia successfully treated with middle meningeal artery embolization (eMMA). We also review the literature to identify management approaches for cSDH with severe thrombocytopenia. Case Description: A 74-year-old male with acute myeloid leukemia presented to the emergency department with persistent headache and emesis following fall without head trauma. Computed tomography (CT) revealed a 12 mm right-sided, mixed density SDH. Platelets were <2000/mm3 initially, which stabilized to 20,000 following platelet transfusions. He then underwent right eMMA without surgical evacuation. He received intermittent platelet transfusions with platelet goal >20,000 and was discharged on hospital day 24 with resolving SDH on CT. Conclusion: High-risk surgical patients with refractory thrombocytopenia and symptomatic cSDH may be successfully treated with eMMA without surgical evacuation. A platelet goal of 20,000/mm3 before and following surgical intervention proved beneficial for our patient. Similarly, a literature review of seven cases of cSDH with comorbid thrombocytopenia revealed five patients undergoing surgical evacuation following initial medical management. Three cases reported a platelet goal of 20,000. All seven cases resulted in stable or resolving SDH with platelets >20,000 at discharge.

Bilateral basal ganglia hemorrhage: a systematic review of etiologies, management strategies, and clinical outcomes.

Bilateral basal ganglia hemorrhages (BBGHs) represent rare accidents, with no clear standard of care currently defined. We reviewed the literature on BBGHs and analyzed the available conservative and surgical strategies. PubMed, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies reporting patients with BBGHs. Clinical characteristics, management, and outcomes were analyzed. We included 64 studies comprising 75 patients, 25 (33%) traumatic and 50 (67%) non-traumatic. Traumatic cases affected younger patients (mean age 35 vs. 46 years, p=0.014) and males (84% vs. 71%, p=0.27) and were characterized by higher proportion of normal blood pressures at admission (66% vs. 13%, p=0.0016) compared to non-traumatic cases. Most patients were comatose at admission (56%), with a mean Glasgow Coma Scale (GCS) score of 7 and a higher proportion of comatose patients in the traumatic than in the non-traumatic group (64% vs. 52%, p=0.28). Among the traumatic group, motor vehicle accidents and falls accounted for 79% of cases. In the non-traumatic group, hemorrhage was most associated with hypertensive or ischemic (54%) and chemical (28%) etiologies. Management was predominantly conservative (83%). Outcomes were poor in 56% of patients with mean follow-up of 8 months. Good recovery was significantly higher in the traumatic than in the non-traumatic group (48% vs. 17%, p=0.019). BBGHs are rare occurrences with dismal prognoses. Standard management follows that of current intracerebral hemorrhage guidelines with supportive care and early blood pressure management. Minimally invasive surgery is promising, though substantial evidence is required to outweigh the potentially increased risks of bilateral hematoma evacuation.

Themes in neuronavigation research: A machine learning topic analysis.

Objective: To understand trends in neuronavigation we employed machine learning methods to perform a broad literature review which would be impractical by manual inspection. Methods: PubMed was queried for articles with "Neuronavigation" in any field from inception-2020. Articles were designated neuronavigation-focused (NF) if "Neuronavigation" was a major MeSH. The latent dirichlet allocation topic modeling technique was used to identify themes of NF research. Results: There were 3896 articles of which 1727 (44%) were designated as NF. Between 1999-2009 and 2010-2020, the number of NF publications experienced 80% growth. Between 2009-2014 and 2015-2020, there was a 0.3% decline. Eleven themes covered 1367 (86%) NF articles. "Resection of Eloquent Lesions" comprised the highest number of articles (243), followed by "Accuracy and Registration" (242), "Patient Outcomes" (156), "Stimulation and Mapping" (126), "Planning and Visualization" (123), "Intraoperative Tools" (104), "Placement of Ventricular Catheters" (86), "Spine Surgery" (85), "New Systems" (80), "Guided Biopsies" (61), and "Surgical Approach" (61). All topics except for "Planning and Visualization", "Intraoperative Tools", and "New Systems" exhibited a monotonic positive trend. When analyzing subcategories, there were a greater number of clinical assessments or usage of existing neuronavigation systems (77%) rather than modification or development of new apparatuses (18%). Conclusion: NF research appears to focus on the clinical assessment of neuronavigation and to a lesser extent on the development of new systems. Although neuronavigation has made significant strides, NF research output appears to have plateaued in the last decade.

Degenerative Spine Surgery in Patients with Parkinson Disease: A Systematic Review.

BACKGROUND: Parkinson disease (PD) has been recognized as responsible for concurrent spinal disorders. Surgical correction may be necessary, but the complexity of such fragile patients may require specific considerations. We systematically reviewed the literature on degenerative spine surgery in patients with PD. METHODS: PubMed, Scopus, Web of Science, and Cochrane were searched according to the PRISMA guidelines to include studies reporting clinical data of patients with PD undergoing degenerative spine surgery. Clinical characteristics, treatment protocols, and outcomes were analyzed. RESULTS: We included 22 articles comprising 442 patients (61.5% female). Mean age was 66.9 ± 3.5 years (range, 41-83 years). Mean PD duration and modified Hoehn and Yahr stage were 4.46 ± 2.39 years and 2.3 ± 0.8, respectively. Operation types included fusion (55.3%) and decompression (41.6%). Mean operated spine levels were 6.0 ± 5.08. A total of 377 postoperative complications occurred in 34.6% patients, categorized into mechanical failure (58.0%), infection (15.1%), or neurologic (10.7%). Of patients, 31.8% required surgical revisions, with an average of 1.88 ± 1.03 revisions per patient. The average normalized presurgery, postsurgery, and final aggregate numeric patient outcome scores were 0.37 ± 0.13, 0.63 ± 0.18, and 0.61 ± 0.19, respectively, with a score of 0 and 1 representing the worst and best possible score. CONCLUSIONS: Degenerative spine surgery in patients with PD is challenging, with complications and revisions occurring in up to a third of treated patients. Surgery should be offered when other treatment options have proved ineffective and is typically reserved for patients with myelopathy or significant disability. Successful outcomes depend on strong interdisciplinary support to control the movement disorder before and after surgery.

Disruption of mTORC1 rescues neuronal overgrowth and synapse function dysregulated by Pten loss.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of AKT/mTOR signaling pathway. Mutations in PTEN are found in patients with autism, epilepsy, or macrocephaly. In mouse models, Pten loss results in neuronal hypertrophy, hyperexcitability, seizures, and ASD-like behaviors. The underlying molecular mechanisms of these phenotypes are not well delineated. We determined which of the Pten loss-driven aberrations in neuronal form and function are orchestrated by downstream mTOR complex 1 (mTORC1). Rapamycin-mediated inhibition of mTORC1 prevented increase in soma size, migration, spine density, and dendritic overgrowth in Pten knockout dentate gyrus granule neurons. Genetic knockout of Raptor to disrupt mTORC1 complex formation blocked Pten loss-mediated neuronal hypertrophy. Electrophysiological recordings revealed that genetic disruption of mTORC1 rescued Pten loss-mediated increase in excitatory synaptic transmission. We have identified an essential role for mTORC1 in orchestrating Pten loss-driven neuronal hypertrophy and synapse formation.

Intrathecal therapy for the management of leptomeningeal metastatic disease: a scoping review of the current literature and ongoing clinical trials.

PURPOSE: Leptomeningeal metastatic disease (LMD) from advanced malignancies has poor prognoses and limited treatments. Intrathecal therapy (ITT) protocols are available, showing variable outcomes. We reviewed the therapeutic and toxicity profiles of ITT in LMD. METHODS: PubMed, EMBASE, Web-of-Science, and Scopus were searched following the PRISMA-ScR guidelines to include studies reporting ITT for LMD. CLINICALTRIAL: gov and Cochrane were searched to identify ongoing clinical trials. RESULTS: We included 27 published studies encompassing 2161 patients and 4 ongoing trials. LMD originated from brain metastases (85.5%), lymphomas (5.4%), high-grade gliomas (4.6%), medulloblastomas (2.3%), and leukemias (2.1%). LMD was mostly diagnosed with the co-presence of neurological-related symptoms and positive imaging and/or cerebrospinal fluid cytology (60.8%). The most common ITT agents were methotrexate (35.9%), cytarabine (21.9%), and thiotepa (8.2%), standalone or combined. Patients received a median of 6.5 ITT cycles (range, 1.0-71.0) via intraventricular (58.8%) or lumbar intrathecal (41.2%) routes. The Ommaya reservoir was implanted in 38.5% cases. Concurrent systemic chemotherapy (45.2%) and/or radiotherapy (30.6%) were used. After 1-3 cycles, 44.7% patients had improved clinical status and 29.9% converted into negative cerebrospinal fluid cytology. The most common ITT-related severe adverse events were neutropenia (6.5%), meningitis (5.2%) and encephalopathy (4.5%). Median freedom from progression was 2.4 months (range, 0.1-59.5) and median overall survival 5.5 months (range, 0.1-148.0). CONCLUSION: Current ITT protocols are variable but effective and well-tolerated in LMD. Ongoing trials are investigating dose-limiting toxicity profiles and long-term overall survival. Future studies should analyze the therapeutic and safety profiles of ITT compared to newer systemic therapies.

Surgical Management of Craniovertebral Junction Schwannomas: A Systematic Review.

BACKGROUND: Craniovertebral junction (CVJ) schwannomas are rare, with surgery and stereotactic radiosurgery (SRS) being effective yet challenging options. We systematically reviewed the literature on CVJ schwannomas. METHODS: PubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA statement to include studies reporting CVJ schwannomas. Clinical features, management, and outcomes were analyzed. RESULTS: We collected 353 patients from 101 included articles. Presenting symptoms were mostly neck pain (30.3%) and headache (26.3%), with most cranial neuropathies involving the XII (31.2%) and X (24.4%) nerves. Most tumors originated from C2 (30.9%) and XII (29.4%) nerves, being extracranial (45.1%) and intradural-extradural (44.2%). Erosion of C1-C2 vertebrae (37.1%), the hypoglossal canal (28.3%), and/or jugular foramen (20.1%) were noted. All tumors were operated, preferably with the retrosigmoid approach (36.5%), with the far-lateral approach (29.7%) or with the posterior approach and cervical laminectomy (26.9%), far-lateral approaches (14.2%), or suboccipital craniotomy with concurrent cervical laminectomy (14.2%). Complete tumor resection was obtained most frequently (61.5%). Adjuvant post-surgery stereotactic radiosurgery was delivered in 5.9% patients. Median follow-up was 27 months (range, 12-252). Symptom improvement was noted in 88.1% of cases, and cranial neuropathies showed improvement in 10.2%. Post-surgical complications occurred in 83 patients (23.5%), mostly dysphagia (7.4%), new cranial neuropathies (6.2%), and cerebrospinal fluid leak (5.9%). A total of 16 patients (4.5%) had tumor recurrence and 7 died (2%), with median overall survival of 2.7 months (range, 0.1-252). CONCLUSIONS: Microsurgical resection is safe and effective for CVJ schwannomas. Data on SRS efficacy and indications are still lacking, and its role deserves further evaluation.

The Role of [68Ga]Ga-DOTA-SSTR PET Radiotracers in Brain Tumors: A Systematic Review of the Literature and Ongoing Clinical Trials.

BACKGROUND: The development of [68Ga]Ga-DOTA-SSTR PET tracers has garnered interest in neuro-oncology, to increase accuracy in diagnostic, radiation planning, and neurotheranostics protocols. We systematically reviewed the literature on the current uses of [68Ga]Ga-DOTA-SSTR PET in brain tumors. METHODS: PubMed, Scopus, Web of Science, and Cochrane were searched in accordance with the PRISMA guidelines to include published studies and ongoing trials utilizing [68Ga]Ga-DOTA-SSTR PET in patients with brain tumors. RESULTS: We included 63 published studies comprising 1030 patients with 1277 lesions, and 4 ongoing trials. [68Ga]Ga-DOTA-SSTR PET was mostly used for diagnostic purposes (62.5%), followed by treatment planning (32.7%), and neurotheranostics (4.8%). Most lesions were meningiomas (93.6%), followed by pituitary adenomas (2.8%), and the DOTATOC tracer (53.2%) was used more frequently than DOTATATE (39.1%) and DOTANOC (5.7%), except for diagnostic purposes (DOTATATE 51.1%). [68Ga]Ga-DOTA-SSTR PET studies were mostly required to confirm the diagnosis of meningiomas (owing to their high SSTR2 expression and tracer uptake) or evaluate their extent of bone invasion, and improve volume contouring for better radiotherapy planning. Some studies reported the uncommon occurrence of SSTR2-positive brain pathology challenging the diagnostic accuracy of [68Ga]Ga-DOTA-SSTR PET for meningiomas. Pre-treatment assessment of tracer uptake rates has been used to confirm patient eligibility (high somatostatin receptor-2 expression) for peptide receptor radionuclide therapy (PRRT) (i.e., neurotheranostics) for recurrent meningiomas and pituitary carcinomas. CONCLUSION: [68Ga]Ga-DOTA-SSTR PET studies may revolutionize the routine neuro-oncology practice, especially in meningiomas, by improving diagnostic accuracy, delineation of radiotherapy targets, and patient eligibility for radionuclide therapies.

Laser Interstitial Thermal Therapy for Cerebral Cavernous Malformations: A Systematic Review of Indications, Safety, and Outcomes.

BACKGROUND: Cerebral cavernous malformations (CCM) in deep eloquent areas present a surgical challenge. Laser interstitial thermal therapy (LITT) may present itself as a safe minimally invasive treatment option. OBJECTIVE: To systematically review the indications, safety, and outcomes of LITT for CCM. METHODS: Electronic databases were searched from inception to October 7, 2021 for articles with CCM and LITT keywords. Studies describing CCMs treated with LITT were included. RESULTS: A total of 32 patients with CCMs in lobar (79%), basal ganglia (12%), and brainstem (9%) locations were treated with LITT. Indications for LITT included drug-resistant seizures (75%), unacceptable surgical risk (22%), recurrent hemorrhage (16%), and early intervention to discontinue antiepileptic drugs (3%). No death or CCM-associated intracranial hemorrhage occurred intraoperatively or postoperatively, and most patients experienced no adverse effects or transient effects that resolved at follow-up (84%). Of those treated for CCM-associated epilepsy, 83% experienced Engel class I seizure freedom and most were class IA (61%). Most patients experienced symptomatic improvement (93%), and a decrease in antiepileptic drugs was reported in more than half of patients (56%), with 28% able to discontinue all antiepilepsy medications after LITT. CONCLUSIONS: LITT seems to be a safe treatment for CCMs located in deep eloquent areas and in lesions presenting with medically refractory seizures or recurrent hemorrhages. Randomized studies are needed to further elucidate its efficacy in treating CCM.

Biological pathways for historical trauma to affect health: A conceptual model focusing on epigenetic modifications.

Despite their unique histories, environments, and lifestyles, historically subjugated populations consistently show poorer health outcomes compared to the general population. The theory of historical trauma, which argues that a collective trauma experienced by one generation can negatively impact the wellbeing of future generations, is a potential framework to understand the adverse health outcomes seen among populations with histories of subjugation. However, the biological pathways through which historical trauma actually impacts health have been unclear. In this paper, we present a cumulative, two pathway model that describes how historical trauma can impact health in contemporary generations. The first pathway suggests that personal exposure to trauma or stressors, which are more common among populations that have experienced historical trauma, can induce epigenetic modifications that can contribute to the development of poor health. The second pathway posits that poor health can occur through intergenerational epigenetic modifications in response to parental and grandparental trauma or stressor exposures. Taken together, these pathways can provide insight into the higher rates of adverse health outcomes among individuals from populations that have historically endured collective trauma. Importantly, the potential reversible nature of epigenetic modifications suggests that these trauma-induced epigenetic effects are not necessarily permanent and that improvements in environmental conditions could reduce the high prevalence of poor health among historically disadvantaged communities.