BRAF-mutated suprasellar glioblastoma mimicking craniopharyngioma: illustrative case.

BACKGROUND: Suprasellar masses commonly include craniopharyngiomas and pituitary adenomas. Suprasellar glioblastoma is exceedingly rare with only a few prior case reports in the literature. Suprasellar glioblastoma can mimic craniopharyngioma or other more common suprasellar etiologies preoperatively. OBSERVATIONS: A 65-year-old male with no significant history presented to the emergency department with a subacute decline in mental status. Work-up revealed a large suprasellar mass with extension to the right inferior medial frontal lobe and right lateral ventricle, associated with significant vasogenic edema. The patient underwent an interhemispheric transcallosal approach subtotal resection of the interventricular portion of the mass. Pathological analysis revealed glioblastoma, MGMT partially methylated, with a BRAF V600E mutation. LESSONS: Malignant glioblastomas can mimic benign suprasellar masses and should remain on the differential for a diverse set of brain masses with a broad range of radiological and clinical features. For complex cases accessible from the ventricle where the pituitary complex cannot be confidently preserved via a transsphenoidal approach, an interhemispheric approach is also a practical initial surgical option. In addition to providing diagnostic value, molecular profiling may also reveal therapeutically significant gene alterations such as BRAF mutations.

Metastatic cervical carcinoma to the brain masquerading as a butterfly glioma: A case report.

Background: Metastatic cervical cancer to the brain is a rare occurrence, representing approximately 1.5% of metastatic cases. We report a rare presentation of cervical cancer with brain metastasis to the corpus callosum. The patient was initially suspected to have a primary glioma but was diagnosed with a metastatic cervical carcinoma lesion through both stereotactic and then opens biopsy. Case Description: A 53-year-old female, with Stage III adenosquamous cervical carcinoma, presented with a large heterogeneously enhancing mass in the corpus callosum body with extension in the cingulate gyrus concerning for glioma. A stereotactic biopsy revealed hypercellular and gliotic brain tissue, while an open biopsy showed an epithelioid neoplasm consistent with metastatic cervical adenosquamous carcinoma. The patient underwent a craniotomy and recovered well and was discharged in stable condition. Conclusion: Brain metastases from cervical cancer are uncommon. We present a rare case of metastatic cervical carcinoma which appeared on imaging to mimic a butterfly glioma. The patient's history and histopathological examination were essential in determining the correct diagnosis and receiving timely treatment.

Barriers to overcoming immunotherapy resistance in glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, known for its poor prognosis and high recurrence rate. Current standard of care includes surgical resection followed by combined radiotherapy and chemotherapy. Although immunotherapies have yielded promising results in hematological malignancies, their successful application in GBM remains limited due to a host of immunosuppressive factors unique to GBM. As a result of these roadblocks, research efforts have focused on utilizing combinatorial immunotherapies that target networks of immune processes in GBM with promising results in both preclinical and clinical trials, although limitations in overcoming the immunosuppressive factors within GBM remain. In this review, we aim to discuss the intrinsic and adaptive immune resistance unique to GBM and to summarize the current evidence and outcomes of engineered and non-engineered treatments targeted at overcoming GBM resistance to immunotherapy. Additionally, we aim to highlight the most promising strategies of targeted GBM immunotherapy combinatorial treatments and the insights that may directly improve the current patient prognosis and clinical care.

Association between spinal stenosis and wild-type ATTR amyloidosis.

Age-related cardiac amyloidosis results from deposits of wild-type tranthyretin amyloid (ATTRwt) in cardiac tissue. ATTR may play a role in carpal tunnel syndrome (CTS) and in spinal stenosis (SS), indicating or presaging systemic amyloidosis. We investigated consecutive patients undergoing surgery for SS for ATTR deposition in the resected ligamentum flavum (LF) and concomitant risk of cardiac amyloidosis. Each surgical specimen (LF) was stained with Congo red, and if positive, the amyloid deposits were typed by mass spectrometry. Patients with positive specimens underwent standard of care evaluation with fat pad aspirates, serum and urine protein electrophoresis with immunofixation, free light-chain assay, TTR gene sequencing and technetium 99 m-pyrophosphate-scintigraphy. In 2018-2019, 324 patients underwent surgery for SS and 43 patients (13%) had ATTR in the LF with wild-type TTR gene sequences. Two cases of ATTRwt cardiac amyloidosis were diagnosed and received treatment. In this large series, ATTRwt was identified in 13% of the patients undergoing laminectomy for SS. Patients with amyloid in the ligamentum flavum were older and had a higher prevalence of CTS, suggesting a systemic form of ATTR amyloidosis involving connective tissue. Further prospective study of patients with SS at risk for systemic amyloidosis is warranted.

Lumbar ligamentum flavum burden: Evaluating the role of ATTRwt amyloid deposition in ligamentum flavum thickness at all lumbar levels.

BACKGROUND: Wild-type transthyretin (ATTRwt) amyloid deposition has been found in the ligamentum flavum (LF) of patients undergoing spinal stenosis surgery. Our group previously reported that ATTRwt amyloid is associated with an increased lumbar ligamentum flavum thickness at symptomatic levels that required surgery. A comprehensive evaluation of LF thickness at asymptomatic levels in addition to symptomatic, treated levels has never been performed in ATTRwt patients. In this study, we compare the total LF thickness of all lumbar levels (lumbar LF burden) in ATTRwt and non-ATTRwt patients. METHODS: We retrospectively identified 177 patients who underwent lumbar spine surgery. Ligamentum flavum thickness of 885 lumbar levels was measured on T2-weighted axial MRI. Amyloid presence was confirmed through Congo red staining of specimens, and subtype of ATTRwt was confirmed using mass-spectrometry and gene sequencing. RESULTS: Of the 177 patients, 30 (16.9%) were found to have ATTRwt in the ligamentum flavum. One hundred and fifty ATTRwt levels and 735 non-ATTRwt levels were measured by four different reviewers, with an intraclass coefficient (ICC) of 0.79. Mean ligamentum flavum thickness was 4.64 (±1.31) mm in the ATTRwt group and 3.99 (±1.45) mm in the non-ATTRwt group (p < 0.001). The lumbar LF burden (sum of ligamentum flavum thickness at all lumbar levels) for ATTRwt patients was 23.22 (±4.48) mm, and for non-ATTRwt patients was 19.96 (±5.49) mm (p = 0.003) CONCLUSION: The lumbar LF burden is greater in patients with ATTRwt amyloid compared to non-ATTRwt patients. This supports prior evidence that ATTRwt amyloid deposition might be associated with increased LF thickness and lumbar stenosis. This potential association requires more research and could be an important finding, as medications have recently become available that can treat patients with ATTRwt amyloid deposition.

Acute Myelopathy: Vascular and Infectious Diseases.

Vascular and infectious causes are rare but important causes of spinal cord injury. High suspicion for these processes is necessary, as symptoms may progress over hours to days, resulting in delayed presentation and diagnosis and worse outcomes. History and clinical examination findings can assist with localization of the affected vascular territory and spinal level, which will assist with focusing spinal imaging. Open and/or endovascular surgical management depends on the associated vascular abnormality. Infectious myelopathy treatment consists of targeted antimicrobial therapy when possible, infectious source control, and again, close monitoring for systemic complications.

Increased thickness of lumbar spine ligamentum flavum in wild-type transthyretin amyloidosis.

BACKGROUND: Wild-type transthyretin (ATTRwt) amyloid deposits have been found in the ligamentum flavum of patients undergoing surgery for spinal stenosis. The relationship between ATTRwt and ligamentum flavum thickness is unclear. We used pre-operative magnetic resonance imaging (MRI) to analyze ligamentum flavum thickness in lumbar spinal stenosis patients with and without ATTRwt amyloid. METHODS: We retrospectively identified 178 patients who underwent lumbar spine surgery. Ligamentum flavum thickness of 253 specimens was measured on T2-weighted axial MRI. Amyloid presence was confirmed through Congo red staining of specimens, and ATTRwt was confirmed using mass-spectrometry and gene sequencing. RESULTS: Twenty four of the 178 patients (13.5%) were found to have ATTRwt in the ligamentum flavum. Forty ATTRwt specimens and 213 non-ATTRwt specimens were measured. Mean ligamentum flavum thickness was 4.92 (±1.27) mm in the ATTRwt group and 4.00 (±1.21) mm in the non-ATTRwt group (p < 0.01). The ligamentum flavum was thickest at L4-L5, with a thickness of 5.15 (±1.27) mm and 4.23 (±1.29) mm in the ATTRwt and non-ATTRwt group, respectively (p = 0.007). There was a significant difference in ligamentum flavum thickness between ATTRwt and non-ATTRwt case for both patients younger than 70 years (p = 0.016) and those older than 70 years (p = 0.004). ATTRwt patients had greater ligamentum flavum thickness by 0.83 mm (95% confidence interval (CI): 0.41-1.25 mm, p < 0.001) when controlled for age and lumbar level. CONCLUSION: Patients with ATTRwt had thicker ligamentum flavum compared to patients without ATTRwt. Further studies are needed to investigate the pathophysiology of ATTRwt in ligamentum flavum thickening.

Is it safe to stop at C7 during multilevel posterior cervical decompression and fusion? - multicenter analysis.

BACKGROUND CONTEXT: Despite a number of studies addressing the anatomical and biomechanical challenges of long segment, posterior cervical fusion surgery, recommendations for appropriate caudal "end level" vary widely. PURPOSE: Compare revision rates, patient reported outcomes and radiographic outcomes in patients in whom 3+ level posterior fusions ended in the cervical spine versus those in whom the fusion was extended into the thoracic spine. STUDY DESIGN: Multicenter retrospective analysis. OUTCOME MEASURES: Visual analog scale (VAS), Oswestry disability index (ODI), cervical lordosis, C2-C7 sagittal plumbline, T1 slope, and revision rate. METHODS: We assembled a radiographic and clinical database of patients that had undergone three or more level posterior cervical fusions for degenerative disease from January 2013 to May 2015 at one of four busy spine centers. Only those patients with at least 2 years of postoperative (postop) follow-up were included. Patients were divided into two groups: group I (fusion ending at C6 or C7) and group II (fusion extending into the thoracic spine). All radiographic measurements (cervical lordosis, T1 slope, and C2-C7 sagittal plumbline) were performed by an independent experienced clinical researcher. RESULTS: Two hundred and sixty-four patient cases were reviewed and sorted into the two outlined groups, Group I (n=168) and Group II (n=96). Demographically, mean age, percentage of females, non-smokers and anterior support were greater in Group II than in Groups I (p<.05). Mean estimated blood loss (EBL), operative time (OR) and length of hospital stay (LOS) were significantly higher in Group II (p<.05). Rate of revision was not clinically or statistically significantly different (p>.05) between Group I (11.1%) and Group II (9.4%). The majority of the revision surgeries occurred between 2 to 5 years postop. A greater number of subjacent degeneration/spondylolisthesis events were noted in Group I compared with Group II (3.6% vs. 1.2%). There were significant improvements in mean clinical outcomes (ie, VAS and ODI) at two years postop in both groups, but there were no statistically significant differences between the groups (p>.05). Mean cervical lordosis at 2 years postop improved in all groups (12.8° vs. 14.1°); however, there was no significant statistical difference in change for mean cervical lordosis (2 weeks vs. 2 year postop) between the two groups. Similary, there were no significant statistical differences in change for mean C2-C7 sagittal plumbline and T1 slope (2 weeks vs. 2 year postop) between the two groups(p>.05). CONCLUSIONS: Caudal end level did not significantly affect revision rates, patient reported outcomes or radiographic outcomes. Higher EBL, OR, and LOS in group II suggest that, absent focal C7-T1 pathology, extension of posterior cervical fusions into the thoracic spine may not be necessary. Extension of posterior cervical fusions into the thoracic spine may be recommended for higher risk patients with limitations to strong C7 bone anchorage. In others, it is safe to stop at C7.

Wild-Type Transthyretin Amyloidosis Occurring in the Ligamentum Flavum of the Cervicothoracic Spine.

BACKGROUND: Wild-type transthyretin amyloid (ATTRwt) has been noted to deposit in the ligamentum flavum of the spine. Prior studies have focused on ATTRwt in the lumbar region, but studies discussing its presence in other levels of the spine are lacking. We report on the presentation of patients with confirmed amyloid in the cervicothoracic regions and discuss the literature to date. METHODS: We retrospectively identified patients at a single institution who underwent surgery for spinal stenosis and had pathologic specimens sent for amyloidosis testing with Congo red staining. ATTRwt was confirmed by the presence of transthyretin amyloid by typing and the absence of mutations in the TTR gene sequence. A final study group of patients with ATTRwt and spinal involvement was established (n = 27). RESULTS: Of 27 patients with amyloid in the spine, 24 (89%) had amyloid present in the lumbar region, 2 (7%) had amyloid in the cervical region, and 1 (4%) had amyloid in the thoracic region. The median age at which patients in the study underwent surgery was 71 years (interquartile range: 9). Spinal stenosis was the indication for surgery in 26 of 27 (96%) patients. Surgery involved 1 or 2 spinal levels in 24 of 27 (89%) patients. CONCLUSIONS: ATTRwt amyloid predominantly deposits in the lumbar region, but it can also be present in the cervical and thoracic regions. While the lumbar regions should remain a focus for evaluation of ATTRwt amyloidosis, the cervicothoracic region should not be ignored.

Complex Management of Hydrocephalus Secondary To Choroid Plexus Hyperplasia.

BACKGROUND: Hyperplasia of the choroid plexus represents a rare cause of communicating hydrocephalus in children. Recent work has associated such disease with genetic abnormalities (such as perturbations in chromosome 9). Given such extensive cerebrospinal fluid (CSF) overproduction, patients with choroid plexus hyperplasia often fail CSF diversion and therefore require adjuvant interventions. CASE DESCRIPTION: We present the case of a male infant with a ventriculoperitoneal shunt and radiographic choroid hyperplasia who presented to our institution with a massive abdominal hydrocele caused by an inability to absorb the significant amount of CSF drainage into the abdomen. CONCLUSION: The child was treated with an endoscopic third ventriculostomy and choroid plexus coagulation; however, he still required CSF diversion via a ventriculoatrial shunt. A genetic workup showed tetraploidy of chromosome 9. We discuss criteria for selection of treatment strategies, including endoscopic third ventriculostomy with choroid plexus coagulation and/or CSF diversion, that may prevent the need for re-operation in select patients with hydrocephalus due to choroid plexus hyperplasia.

Where Neurosurgery Meets Heart Failure: A Case Report of a Patient with Amyloid Transthyretin Wild Type in the Ligamentum Flavum and Cardiac Tissue with Bilateral Carpal Tunnel Syndrome.

BACKGROUND: Transthyretin wild-type (ATTRwt) amyloidosis is a systemic process resulting in deposition of misfolded transthyretin protein in several different tissues throughout the body. It is known to be a cause of progressive, life-threatening cardiomyopathy and lumbar spinal stenosis and carpal tunnel syndrome. CASE DESCRIPTION: Here we present the case of a 71-year-old man who has clinical manifestations of all 3 entities over several years, providing a picture of the natural history of ATTRwt amyloidosis. This patient eventually underwent a heart transplant because of progressive cardiac amyloidosis (CA) resulting in end-stage heart failure. However, symptoms in carpal tunnel and lumbar spine manifested years before the symptoms of heart failure. ATTRwt amyloidosis may present as a clinical triad of lumbar stenosis, carpal tunnel syndrome, and heart failure. Recently developed medications have shown efficacy in slowing the progress of systemic and cardiac amyloidosis. CONCLUSIONS: Knowing that extracardiac symptoms may occur first, we propose that sending ligamentum flavum and flexor tenosynovium for pathologic evaluation may be a unique opportunity to screen and treat a population of patients at risk for developing CA and heart failure.

Deep brain stimulation for Tourette syndrome: a single-center series.

OBJECTIVE Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by multiple motor and phonic tics. While pharmacological and behavioral therapy can be effective in most patients, a subset of patients remains refractory to treatment. Increasing clinical evidence from multiple centers suggests that deep brain stimulation (DBS) of the medial thalamus can be effective in many cases of refractory TS. METHODS The authors retrospectively reviewed outcomes in 13 patients with refractory TS who underwent medial thalamic DBS performed by their team over a 7-year period. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive Compulsive Scale. YGTSS scores were calculated at visits immediately postoperatively and at the most recent follow-up in patients with a minimum of 6 months of postoperative follow-up. Coordinates of the active DBS contacts were calculated and projected onto each patient's pre- and postoperative images. RESULTS Patients showed an average decrease of 37% (p = 0.0063) in the total tic severity at their first postoperative visit. At their latest visit, their scores achieved significance, decreasing from preoperative scores by an average of 50% (p = 0.0014). The average position of the active contact was noted to be at the junction of the posterior ventralis oralis internus/centromedian-parafascicular nuclei. Device-related complications occurred in 2 patients, necessitating additional surgeries. All patients continued to use the system at last follow-up. CONCLUSIONS The authors' data are consistent with the small but growing body of literature supporting DBS of the ventralis oralis internus/centromedian-parafascicular thalamus as an effective and relatively safe treatment for severe, refractory TS.

Sensitive electrochemical immunosensor for matrix metalloproteinase-3 based on single-wall carbon nanotubes.

A novel electrochemical immunosensor for the detection of matrix metalloproteinase-3 (MMP-3), a cancer biomarker protein, based on vertically aligned single-wall carbon nanotube (SWCNT) arrays is presented. Detection was based on a sandwich immunoassay consisting of horseradish peroxidase (14-16 labels) conjugated to a secondary antibody and/or a polymer bead loaded with multi-enzyme labels. Performance was optimized by effective minimization of non-specific binding (NSB) events using Bovine serum albumin (BSA), Tween-20 and optimization of the primary antibody and secondary antibody concentrations. Results provided a detection limit of 0.4 ng mL(-1) (7.7 pM) for the 14-16 label sensor protocol and 4 pg mL(-1) (77 fM) using a multiply enzyme labeled polymeric bead amplification strategy in 10 microL of calf serum. This immunosensor based on SWCNT arrays offers great promise for a rapid, simple, cost-effective method for clinical screening of cancer biomarkers for point-of-care diagnosis.