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1. Benjamini D, Priemer DS, Perl DP, Brody DL, Basser PJ. Mapping astrogliosis in the individual human brain using multidimensional MRI. Brain. Published online August 12, 2022:5-6. doi:10.1093/brain/awac298

There are currently no noninvasive imaging methods available for astrogliosis assessment or mapping in the central nervous system despite its essential role in the response to many disease states, such as infarcts, neurodegenerative conditions, traumatic brain injury, and infection. Multidimensional MRI is an increasingly employed imaging modality that maximizes the amount of encoded chemical and microstructural information by probing relaxation (T1 and T2) and diffusion mechanisms simultaneously. The authors use the exquisite sensitivity of this modality to derive a signature of astrogliosis and disentangle it from normative brain at the individual level using machine learning. They investigated ex vivo cerebral cortical tissue specimens derived from seven subjects who sustained blast induced injuries, which resulted in scar-border forming astrogliosis without being accompanied by other types of neuropathologic abnormality, and from seven control brain donors. By performing a combined postmortem radiology and histopathology correlation study they found that astrogliosis induces microstructural and chemical changes that are detected with multidimensional MRI, and which can be attributed to astrogliosis because no axonal damage, demyelination, or tauopathy were histologically observed in any of the cases in the study. Importantly, they showed that no one-dimensional T1, T2, or diffusion MRI measurement can disentangle the microscopic alterations caused by this neuropathology. Based on these finding, they developed a within-subject anomaly detection procedure that generates MRI-based astrogliosis biomarker maps ex vivo, which were significantly and strongly correlated with co-registered histological images of increased glial fibrillary acidic protein deposition. The findings elucidate the underpinning of MRI signal response from astrogliosis, and the demonstrated high spatial sensitivity and specificity in detecting reactive astrocytes at the individual level, and if reproduced in vivo, will significantly impact neuroimaging studies of injury, disease, repair, and aging.

7 figures, 1 table

2. Salih M, Enriquez-Marulanda A, Khorasanizadeh M, Moore J, Prabhu VC, Ogilvy CS. Cerebrospinal Fluid Shunting for Idiopathic Intracranial Hypertension: A Systematic Review, Meta-Analysis, and Implications for a Modern Management Protocol. Neurosurgery. 2022;91(4):529-540. doi:10.1227/neu.0000000000002086

This systematic review and meta-analysis assessed the outcome after CSF shunting for IIH by analyzing the published literature on the topic over a period of approximately 21 years. Although these are largely retrospective observational studies with some heterogeneity, a total of 372 patients from 15 studies were available for analysis. They selected the 3 cardinal and most disabling symptoms for this review; although other symptoms such as diplopia due to a sixth nerve palsy and pulsatile tinnitus may be noted, they are not consistently reported. They focused on headache, papilledema, and visual impairment for meta-analysis because most studies reported outcomes for these 3 symptoms and physical signs. The results of this study indicate that the most significant improvement was seen in papilledema; almost 96% of patients were noted to have an improvement in papilledema with CSF shunting. Headache also showed substantial improvement, with a 91% rate of improvement. Improvement of visual symptoms was noted in 85%.

Procedural complications and long-term durability of CSF shunting was also assessed. Intraprocedural complications and periprocedural infection or hemorrhage were not reported in any study. 12 studies reported periprocedural low-pressure headache due to CSF overdrainage. In most cases, original headache of patients improved for a short period of time after shunting, and they subsequently developed a headache that was related to body position. The overall occurrence rate of low-pressure headache was 20%. This may also be related to the relatively high rate of LP shunt placement that was observed in this analysis. There were no reports of malpositioned catheters or intracranial complications noted on cranial computed tomography (CT) in these patients. Overall, the most common reason for revision was catheter obstruction with recurrence of symptoms and signs of increased intracranial pressure. Other reasons for revision included abdominal catheter migration and infection.

Current management protocols were also discussed. Neuroimaging evaluation includes a high-quality MR and signs suggestive of IIH include flattening of the posterior scleral margins, widening of the peri-optic CSF space, tortuosity of the optic nerves, “empty-sella,” cerebellar tonsillar descent, and very small or slit-like ventricles. This is complemented by an MRV study to assess the status of the intracranial venous sinus pathways and look for any focal stenosis, atresia, or other venous abnormalities that may predispose an individual to developing IIH. If no contraindications exist, this is followed by a lumbar puncture (LP) to assess the opening CSF pressure and also allow removal of CSF from the lumbar subarachnoid cistern to ascertain any therapeutic benefit from CSF drainage. Routine CSF studies are also performed, and the patient is followed in clinic in 1 to 2 weeks to assess the response to CSF drainage. The diagnosis of IIH is confirmed by this collation of clinical symptomatology, neurological and ophthalmological evaluations, LP, and neuroimaging studies.

6 figures, 3 tables, no imaging

3. Lehrer EJ, Ahluwalia MS, Gurewitz J, et al. Imaging-defined necrosis after treatment with single-fraction stereotactic radiosurgery and immune checkpoint inhibitors and its potential association with improved outcomes in patients with brain metastases: an international multicenter study of 697 patients. J Neurosurg. Published online September 1, 2022:1-10. doi:10.3171/2022.7.JNS22752

Brain metastasis is the most common intracranial neoplasm. Conservative estimates indicate that a brain metastasis will be diagnosed in 10%–30% of cancer patients at some time during their disease course. Historically, these patients had a poor prognosis with a median overall survival (OS) of approximately 3.5 months. Treatment also consisted of a multimodal approach involving corticosteroids, resection, and whole-brain radiation therapy (WBRT). Treatment-related morbidity has markedly decreased in recent years because of the widespread adoption of stereotactic radiosurgery (SRS) and the incorporation of memantine and hippocampal avoidance in WBRT. Furthermore, improved systemic therapies, such as immune checkpoint inhibitors (ICIs), have demonstrated an improvement in OS across multiple advanced malignancies, such as non–small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC), and they are now widely used in this setting.

Multiple retrospective single-institution studies have demonstrated that OS is improved when SRS is combined with ICIs, particularly when these therapies are administered within 4 weeks of one another. A complication of SRS is the development of radiation necrosis (RN), which can be associated with significant neurological morbidity with roughly 50% of patients being symptomatic. The incidence of RN following SRS ranges from 5% to 25%, with different studies using various diagnostic criteria ranging from pathological tissue diagnosis to imaging changes. Multiple factors have demonstrated an association with RN, such as dose-volume relationships, previous WBRT, use of systemic therapies, and choice of radiosurgery platform. Furthermore, the use of ICIs has demonstrated a strong association with the development of RN.

There were 697 patients with 4536 brain metastases with a median follow-up of 13.6 months who were included in the analysis. Treatment-related imaging changes (TRICs) were diagnosed in 9.8% of patients, and MRI was the diagnostic modality in 97.1% of the patients. The median number of brain metastases per patient was 3. The median age was 66 years, and 54.1% of patients were male. Primary tumor histology was NSCLC, melanoma, and RCC in 57.3%, 36.3%, and 6.4% of cases, respectively. TRICs were classified using MRI, PET, MR spectroscopy, or biopsy findings. MRI findings, such as contrast enhancement and perilesional edema, as well as specific enhancement patterns such as a “soap bubble” and “Swiss cheese” appearance, were noted. Although PET and MR spectroscopy were used in a minority of cases, the radiotracer standardized uptake value and choline/creatinine ratios were noted for PET and MR spectroscopy imaging, respectively