Clinical presentation, magnetic resonance imaging findings, and outcome of 80 Dachshunds with cervical intervertebral disc extrusion.

Introduction: Large clinical studies regarding cervical intervertebral disc extrusion (IVDE) in Dachshunds are lacking. This retrospective multicentric study therefore aims to describe the clinical features, magnetic resonance imaging (MRI) findings and outcomes of Dachshunds diagnosed with cervical IVDE. Methods: Medical records of Dachshunds with cervical IVDE were reviewed for signalment, onset of clinical signs, neurological examination, MRI features, treatment and outcome. Results: Eighty Dachshunds were included in the study, mostly ambulatory (55% grade 1 and 33% grade 2) and without nerve root signature (85% of cases) on presentation. Information on coat type was available for 56% of dogs; specifically, 41% were smooth-haired, 9% were long-haired and 6% were wire-haired Dachshunds. There were 29 (36%) neutered female, 27 (34%) male entire, 15 (19%) male neutered and 9 (11%) entire female dogs. The onset of clinical signs was most often >48 h (84%). The most common intervertebral disc space affected was C2-C3 (38%) and foraminal IVDEs were reported in 14% of dogs. A foraminal IVDE was diagnosed in only 25% of dogs presented with nerve root signatures. Most dogs (77.5%) were treated surgically. In this group, a higher body condition score on presentation and a higher mean spinal cord compression ratio calculated on MRI were directly and moderately associated with a longer hospitalization time (r = 0.490 p = 0.005 and r = 0.310 p = 0.012, respectively). The recovery time was longer in dogs with an onset of clinical signs <24 h or 24-48 h compared to those with an onset of clinical signs >48 h (3.1 ± 6.5 days versus 1.6 ± 6.2, p < 0.001) in both medically and surgically treated groups. Data about the outcome was available for 83% of dogs. Eighty percent of the entire population of dogs was considered to have completely returned to normal. There was no association between the therapeutic choice (surgical versus medical management) and the outcome of the dogs included in this study.

A case of disseminated spinal astroblastoma harboring a MAMLD1::BEND2 fusion.

Astroblastoma, MN1-altered, is a rare neoplasm of the central nervous system (CNS). This malignancy shares similar histopathological features with other CNS tumors, including ependymomas, making it challenging to diagnose. DNA methylation profiling is a new and robust technique that may be used to overcome this diagnostic hurdle. We report the case of a now 25-year-old female diagnosed with what was initially called an ependymoma located in the cervical spine at the age of 2 years old. After initial resection, the tumor recurred multiple times and within 2 years of diagnosis had disseminated disease throughout the brain and spinal cord. She has now undergone over two decades of treatment, including multiple surgical resections, radiation therapy, and administration of numerous chemotherapeutic agents. In 2021, the patient presented to our institution with lumbosacral radicular symptoms due to enlarging lesions within the lumbosacral spine. Reexamination of formalin-fixed, paraffin-embedded material from the patient's tumor using genomic DNA methylation profiling resulted in a diagnostic change from grade III anaplastic ependymoma to astroblastoma, MN1-altered. This work describes another confirmed case of astroblastoma, MN1-altered, to the growing body of literature.

Relationship between magnetic resonance imaging findings and histological grade in spinal peripheral nerve sheath tumors in dogs.

BACKGROUND: Peripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location. HYPOTHESIS/OBJECTIVES: Identify magnetic resonance imaging (MRI) features predictive of PNST histologic grade. ANIMALS: Forty-four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation. METHODS: A multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board-certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board-certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis. RESULTS: Forty-four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low-grade), 19 were PNSTs Grade 2 (medium-grade), and 9 were PNSTs Grade 3 (high-grade). Large volume (P = .03) and severe peripheral contrast enhancement (P = .04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade. CONCLUSIONS AND CLINICAL IMPORTANCE: Grade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high-grade PNSTs including tumor size and peripheral contrast enhancement.

The role of the dura mater in cerebral metastases.

OBJECTIVE: The objective of this review was to describe the immunological changes that take place in the dura mater in response to metastatic disease that seeds the CNS. The authors hypothesized that the dura's anatomy and resident immune cell population play a role in enabling metastasis to the brain and leptomeninges. METHODS: An extensive literature search was conducted to identify evidence that supports the dura's participation in metastasis to the CNS. The authors' hypothesis was informed by a recent upsurge in studies that have investigated the dura's role in metastatic development, CNS infections, and autoimmunity. They reviewed this literature as well as the use of immunotherapy in treating brain metastases and how these therapies change the meningeal immune landscape to overcome and reverse tumor-promoting immunosuppression. RESULTS: Evidence suggests that the unique architecture and immune cell profile of the dura, compared with other immune compartments within the CNS, facilitate entry of metastatic tumor cells into the brain. Once these tumor cells penetrate the dural barrier, they propagate an immunosuppressive tumor microenvironment. Therefore, immunotherapy may serve to overcome this immunosuppressive environment and liberate proinflammatory immune cells in an effort to combat metastatic disease. CONCLUSIONS: Within the next few years, the authors expect the addition of several more scientific studies into the literature that further underscore the dura as a chief participant and neuroanatomical barrier in neuro-oncology.

Dural Closure Techniques and Cerebrospinal Fluid Leak Incidence After Resection of Primary Intradural Spinal Tumors: A Systematic Review.

STUDY DESIGN: This is a systematic review of primary intradural spinal tumors (PIDSTs) and the frequency of postoperative cerebrospinal fluid (CSF) leaks. OBJECTIVE: This study aimed to compare CSF leak rates among techniques for dural watertight closure (WTC) after the resection of PIDSTs. SUMMARY OF BACKGROUND DATA: Resection of PIDSTs may result in persistent CSF leak. This complication is associated with infection, wound dehiscence, increased length of stay, and morbidity. Dural closure techniques have been developed to decrease the CSF leak rate. METHODS: A PubMed search was performed in 2022 with these inclusion criteria: written in English, describe PIDST patients, specify the method of dural closure, report rates of CSF leak, and be published between 2015 and 2020. Articles were excluded if they had <5 patients. We used standardized toolkits to assess the risk of bias. We assessed patient baseline characteristics, tumor pathology, CSF leak rate, and dural closure techniques; analysis of variance and a 1-way Fisher exact test were used. RESULTS: A total of 4 studies (201 patients) satisfied the inclusion criteria. One study utilized artificial dura (AD) and fibrin glue to perform WTC and CSF diversion, with lumbar drainage as needed. The rate of CSF leak was different among the 4 studies (P=0.017). The study using AD with dural closure adjunct (DCA) for WTC was associated with higher CSF leak rates than those using native dura (ND) with DCA. There was no difference in CSF leak rate between ND-WTC and AD-DCA, or with any of the ND-DCA studies. CONCLUSIONS: After resection of PIDSTs, the use of autologous fat grafts with ND resulted in lower rates of CSF leak, while use of fibrin glue and AD resulted in the highest rates. These characteristics suggest that a component of hydrophobic scaffolding may be required for WTC. A limitation included articles with low levels of evidence. Continued investigation to understand mechanisms for WTC is warranted. LEVEL OF EVIDENCE: Level 3.

Glioblastoma may evade immune surveillance through primary cilia-dependent signaling in an IL-6 dependent manner.

Glioblastoma is the most common, malignant primary brain tumor in adults and remains universally fatal. While immunotherapy has vastly improved the treatment of several solid cancers, efficacy in glioblastoma is limited. These challenges are due in part to the propensity of glioblastoma to recruit tumor-suppressive immune cells, which act in conjunction with tumor cells to create a pro-tumor immune microenvironment through secretion of several soluble factors. Glioblastoma-derived EVs induce myeloid-derived suppressor cells (MDSCs) and non-classical monocytes (NCMs) from myeloid precursors leading to systemic and local immunosuppression. This process is mediated by IL-6 which contributes to the recruitment of tumor-associated macrophages of the M2 immunosuppressive subtype, which in turn, upregulates anti-inflammatory cytokines including IL-10 and TGF-ß. Primary cilia are highly conserved organelles involved in signal transduction and play critical roles in glioblastoma proliferation, invasion, angiogenesis, and chemoradiation resistance. In this perspectives article, we provide preliminary evidence that primary cilia regulate intracellular release of IL-6. This ties primary cilia mechanistically to tumor-mediated immunosuppression in glioblastomas and potentially, in additional neoplasms which have a shared mechanism for cancer-mediated immunosuppression. We propose potentially testable hypotheses of the cellular mechanisms behind this finding.

Endolymphatic sac tumor in an 8-month-old cat.

Background: The endolymphatic sac is an organ devoid of sensory receptors. It is connected with the endolymphatic compartment and contains endolymph. Endolymphatic sac tumor (ELST) is a rare neoplasm involving the middle and inner ear described in humans and dogs that does not show cellular characteristics of malignancy, but can be locally invasive and involve destruction of the temporal bone and adjacent structures. Case Description: An 8-month-old female cat was referred because of sudden onset of vestibular signs starting 3 days prior to referral. On clinical examination, the patient showed depression, right head tilt, left-sided facial paralysis, and horizontal nystagmus with fast phase to the left. The magnetic resonance images showed a voluminous extra-axial lesion, with irregular morphology and well-defined margins, with intracranial extension in the region of the pons, rostral medulla oblongata, cerebellar vermis, floccule, and left cerebellar hemisphere. Due to progressive clinical deterioration, the cat was euthanized 2 weeks later. A necropsy was then performed and histological samples were taken. The necropsy revealed the presence of a voluminous dark red irregular mass extending from the tympanic bulla to the posterior cranial fossa following the left glossopharyngeal nerve. The histopathological exam of the extra-axial lesion featured a nonencapsulated, moderately cellular, rather loose, proliferation of cuboidal to columnar epithelium breaching through chunks of an otherwise normal appearing dura mater and invading some cranial nerves. Sections of the cerebellum and brainstem revealed moderate, focal, impingement of the parenchyma with a very mild extension of the proliferating cells into the ventral left side of the medulla oblongata. Based on these histological characteristics, the lesion was defined as ELST, a rare neoplasm described in human beings and with two reports in dogs. Conclusion: To our knowledge, this is the first report describing an ELST in a cat.

Agreement of surgeon's perception of the effectiveness of spinal cord decompression with findings on postoperative magnetic resonance imaging for dogs surgically treated for intervertebral disk extrusion.

OBJECTIVE: To determine the accuracy of the surgeon's perception versus postoperative MRI findings in assessing the effectiveness of spinal cord decompression achieved in dogs surgically treated for intervertebral disk extrusion (IVDE) and whether postoperative MRI findings were more likely to be associated with various outcomes. ANIMALS: 68 dogs surgically treated for cervical or thoracolumbar IVDE. PROCEDURES: Data on clinical, neurologic, pre- and postoperative MRI, and intraoperative findings as well as outcomes and recovery times (6-month follow-up period) were prospectively collected and compared between various groups. RESULTS: 54 (79%) dogs had thoracolumbar IVDE, and 14 (21%) had cervical IVDE. Median degree of spinal cord compression as assessed on transverse T2-weighted MRI images was 45.6% before surgery and 8.8% after surgery. The correlation between surgeons' perception (n = 3) and postoperative MRI findings for the degree of spinal cord decompression achieved was only fair (κ = 0.40). Unsatisfactory spinal cord decompression as assessed via postoperative MRI was associated with severity of preoperative neurologic grade and preoperative compression, thoracolumbar (vs cervical) IVDE, and ventral (vs ventrolateral or dorsolateral) circumferential distribution of extruded material. Satisfactory (vs unsatisfactory) decompression as assessed via MRI was associated with a lower postoperative neurologic grade, greater likelihood of a successful outcome, and lower mean recovery time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that for dogs surgically treated for IVDE, the surgeon's perception of adequate spinal cord decompression may be less reliable than postoperative MRI findings. Postoperative MRI appeared particularly useful for dogs with a severe preoperative neurologic status, severe preoperative spinal cord compression, and thoracolumbar IVDE.

Basal Autophagy Is Altered in Lagotto Romagnolo Dogs with an ATG4D Mutation.

A missense variant in the autophagy-related ATG4D-gene has been associated with a progressive degenerative neurological disease in Lagotto Romagnolo (LR) dogs. In addition to neural lesions, affected dogs show an extraneural histopathological phenotype characterized by severe cytoplasmic vacuolization, a finding not previously linked with disturbed autophagy in animals. Here we aimed at testing the hypothesis that autophagy is altered in the affected dogs, at reporting the histopathology of extraneural tissues and at excluding lysosomal storage diseases. Basal and starvation-induced autophagy were monitored by Western blotting and immunofluorescence of microtubule associated protein 1A/B light chain3 (LC3) in fibroblasts from 2 affected dogs. The extraneural findings of 9 euthanized LRs and skin biopsies from 4 living affected LRs were examined by light microscopy, electron microscopy, and immunohistochemistry (IHC), using antibodies against autophagosomal membranes (LC3), autophagic cargo (p62), and lysosomal membranes (LAMP2). Biochemical screening of urine and fibroblasts of 2 affected dogs was performed. Under basal conditions, the affected fibroblasts contained significantly more LC3-II and LC3-positive vesicles than did the controls. Morphologically, several cells, including serous secretory epithelium, endothelial cells, pericytes, plasma cells, and macrophages, contained cytoplasmic vacuoles with an ultrastructure resembling enlarged amphisomes, endosomes, or multivesicular bodies. IHC showed strong membranous LAMP2 positivity only in sweat glands. The results show that basal but not induced autophagy is altered in affected fibroblasts. The ultrastructure of affected cells is compatible with altered autophagic and endo-lysosomal vesicular traffic. The findings in this spontaneous disease provide insight into possible tissue-specific roles of basal autophagy.

Role of image guided radiation therapy in obese patients with gynecologic malignancies.

PURPOSE: We investigated the effect of body mass index on setup errors by analyzing daily shifts required in treating patients undergoing image guided radiation therapy (IGRT) for gynecologic malignancies. METHODS AND MATERIALS: Forty successive patients treated with daily kV-based IGRT for gynecologic malignancies between April 2009 and June 2012 were identified. Directional setup corrections were analyzed according to patient body mass index. Random and systematic setup errors were calculated. Image acquisition dose was estimated by performing ionization chamber measurements in a phantom. RESULTS: Obese patients had larger random setup errors, particularly in the right-left (R-L) direction, with a setup error of 7.6 mm, versus 3.9 mm for nonobese patients. The range of individual patient random errors in the R-L direction was 1.5 to 7.6 mm among nonobese patients versus 2.0 to 17.0 mm among obese patients (P = .03, F-test). For obese patients, daily IGRT prevented treating outside the planning target volume in 33% of fractions, versus 16% in the nonobese group (P = .001). The mean total image acquisition dose from daily kV-IGRT was approximately 3 cGy, versus 150 cGy if daily megavoltage portal imaging were used to correct for erratic setup errors. CONCLUSIONS: Daily kV-based IGRT in obese patients allows for correction of erratic setup error and minimizes excess dose from portal imaging.