Lentiviral-Induced Spinal Cord Gliomas in Rat Model.

Intramedullary spinal cord tumors are a rare and understudied cancer with poor treatment options and prognosis. Our prior study used a combination of PDGF-B, HRAS, and p53 knockdown to induce the development of high-grade glioma in the spinal cords of minipigs. In this study, we evaluate the ability of each vector alone and combinations of vectors to produce high-grade spinal cord gliomas. Eight groups of rats (n = 8/group) underwent thoracolumbar laminectomy and injection of lentiviral vector in the lateral white matter of the spinal cord. Each group received a different combination of lentiviral vectors expressing PDGF-B, a constitutively active HRAS mutant, or shRNA targeting p53, or a control vector. All animals were monitored once per week for clinical deficits for 98 days. Tissues were harvested and analyzed using hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining. Rats injected with PDGF-B+HRAS+sh-p53 (triple cocktail) exhibited statistically significant declines in all behavioral measures (Basso Beattie Bresnahan scoring, Tarlov scoring, weight, and survival rate) over time when compared to the control. Histologically, all groups except the control and those injected with sh-p53 displayed the development of tumors at the injection site, although there were differences in the rate of tumor growth and the histopathological features of the lesions between groups. Examination of immunohistochemistry revealed rats receiving triple cocktail displayed the largest and most significant increase in the Ki67 proliferation index and GFAP positivity than any other group. PDGF-B+HRAS also displayed a significant increase in the Ki67 proliferation index. Rats receiving PDGF-B alone and PDGF-B+ sh-p53 displayed more a significant increase in SOX2-positive staining than in any other group. We found that different vector combinations produced differing high-grade glioma models in rodents. The combination of all three vectors produced a model of high-grade glioma more efficiently and aggressively with respect to behavioral, physiological, and histological characteristics than the rest of the vector combinations. Thus, the present rat model of spinal cord glioma may potentially be used to evaluate therapeutic strategies in the future.

Spontaneous Subarachnoid Haemorrhage in Spinal Hemangioblastoma: Illustrative Case and Discussion of a Pathophysiological Hypothesis.

Spontaneous non-aneurysmal subarachnoid haemorrhage (naSAH) is an unusual finding that could be burdened by significant mortality and morbidity rates. Rare pathologies and delayed diagnosis could be advocated as responsible of unfavourable outcomes. Herein, we describe an exceedingly rare giant lumbar spinal hemangioblastoma (80 × 23 mm) presenting as an intracranial naSAH. Based on our radiological and clinical findings a pathophysiological hypothesis linking intracranial naSAH to venous hypertension was discussed for the first time even among lumbar spinal tumors. Although rare, unusual causes should be investigated in presence of radiological atypical finding as a prompt evaluation and treatment could be needed.

Functional Outcomes and Temporal Profile of Recovery in Patients with Intradural Extramedullary Spinal Cord Tumors with Poor Nurick Grade.

BACKGROUND: Patients with spinal intradural extramedullary (IDEM) tumors usually have a good functional outcome after tumor excision. However, the literature is sparse on the functional outcome in patients with poor Nurick grade (NG 4 and 5). METHODS: A retrospective review of 81 patients with IDEM tumors presenting with a poor NG was performed to determine postoperative functional outcome and the temporal pattern of recovery. The following risk factors were analyzed: preoperative NG, duration of symptoms, tumor location, peritumoral edema, presence of syrinx, and tumor type. RESULTS: Neurologic function started recovering soon after surgery, with >80% of the patients improving by ≥1 grade at the end of 1 week after surgery. Of the 66 patients available for follow-up of >6 months after surgery, 63 (95.5%) improved to NG 0-2 and 51 (77.2%) became asymptomatic (NG 0 or 1). Three patients had a poor functional outcome on follow-up of >31 months; 2 had improved from NG 5 to NG 4, whereas 1 patient continued to be in NG 4. Factors associated with a poor outcome were an upper thoracic location (P = 0.025) and presence of a syrinx (P = 0.004). None of the patients had bladder dysfunction at follow-up of >6 months. CONCLUSIONS: After excision of spinal IDEM tumors, in patients who present with a poor neurologic function (NG 4 and 5), good functional outcome (NG 0-2) can be expected in >95% of patients. No recovery can be anticipated beyond 1 year after surgery.

The case of a 61-year-old man with unusual headaches.

A 61-year-old man with past medical history significant for prediabetes, hyperlipidemia and high-grade prostate intraepithelial neoplasia presents with headaches for one month. Imaging of his brain reveals hydrocephalus and spine imaging reveals a cord lesion. These findings are discussed further in the case.

The case of a 37-year-old male with trouble ambulating and incontinence.

A 37 year-old previously healthy man from Jamaica presented with 2-3 months of progressive trouble ambulating and incontinence. By 1 month prior to arrival he was wheelchair bound and unable to ambulate even with assistance. He started to wear a diaper for bladder and bowel incontinence. He also complained of painless numbness in his legs over the same period of time. His exam is notable for marked weakness and spasticity in his legs, with hyper-reflexia and clonus. He has a sensory level at the level of the umbilicus. An MRI shows a longitudinally extensive T2 signal change throughout the thoracic cord. His cerebrospinal fluid is mildly inflammatory. His HTLV-1 antibody test is reactive.

Primary Lumbar Paraganglioma: Clinical, Radiologic, Surgical, and Histopathologic Characteristics from a Case Series of 13 Patients.

BACKGROUND: Paragangliomas are uncommon neuroendocrine tumors, rarely occurring in the lumbar spine. Primary lumbar paragangliomas are prominently vascularized, can present variably, and pose both diagnostic and surgical challenges. We report on a large case series with long-term follow-up and intraoperative footage to characterize the natural history, diagnostic approach, and operative approach to this rare surgical disease. METHODS: This is a single-center, retrospective cohort study including all patients with histologically confirmed primary lumbar paraganglioma treated at our tertiary neurosurgical center between 1997 and 2018. Clinical, radiologic, surgical, and histologic data were collected from medical records. RESULTS: There were 13 cases of primary lumbar paraganglioma (8 men [61.5%], 5 women [38.5%]; mean age, 51.3 years; range, 33.2-68.9 years). Symptom duration correlated with tumor size (Spearman r = 0.735, P = 0.01). The main presenting symptoms were lower back pain and radiculopathy, often long-standing with recent deterioration. Seven patients (53.8%) were admitted as emergency cases, including 3 with cauda equina syndrome. Preoperative differential diagnoses included nerve sheath tumor, ependymoma, meningioma, and disk herniation. The mean Ki-67 mitotic index was 5.7% (range, 1%-10%). Surgical resection improved pain in 8 of 13 patients (61.5%) and weakness improved in 5 of 5 patients (100%). CONCLUSIONS: Primary lumbar paragangliomas are rare neoplasms of the cauda equina that typically progress slowly but may also present acutely. They are often related to the filum terminale, which should be resected prior to other attachments intraoperatively to prevent displacement of the tumor out of view. Total resection can be curative, and long-term follow-up in this series found no recurrence.

An institutional review of 10 cases of spinal hemangiopericytoma/solitary fibrous tumor.

BACKGROUND: Spinal hemangiopericytoma is very rare tumors with only a few case reports and one case series. We have treated ten patients between 2004 and 2017 and, thus, present a retrospective review of our patients with a focus on clinical presentation, radiological features, management, pathology, and outcome. MATERIALS AND METHODS: Histopathological data were reviewed in all the cases and clinical and follow-up details were collected from data available in our department. RESULTS: There were five males and five females, including one pediatric patient. The mean age of the patients was 34.7 years (Range 12-52 years). Dorsal, cervical, and lumbar spine involvement were found in five, four, and one patient, respectively. Intradural extramedullary tumor was the most common tumor and all patients presented motor weaknesses. Gross total resection of the tumor was done in seven patients and six patients received postoperative radiotherapy. Histopathology showed anaplastic tumor in two cases with high MIB-1 labelling index. Most patients were positive for CD34, vimentin, mic-2, and bcl-2. While the seven patients who underwent gross total resection improved significantly and were self-ambulatory in the follow-up period, two patients who underwent subtotal resection expired due to tumor metastasis. CONCLUSION: Spinal hemangiopericytoma is a very rare tumor. We present a series of cases treated at our institute for the same. Gross total resection is the goal and radiotherapy should be given in case of residual tumor or high-grade tumors. Prognosis is good after gross total excision and functional recovery can be expected in most patients.

Spinal Intramedullary Epidermoid Cyst: Case Report and Updated Literature Review.

BACKGROUND: Epidermoid cysts are rare benign neoplasms within the neuroaxis and account for <1% of all intraspinal tumors. They can be congenital or acquired. Being a slow-growing tumor, the clinical presentation is widely variable depending on the location, size, or age of the patient. OBJECTIVES: Because of the rarity of this entity, the diagnosis and treatment are often delayed. We wanted to offer an updated overall view on spinal epidermoid cysts to facilitate diagnosis and treatment decisions. METHODS: We present the case of a patient with thoracic intramedullary epidermoid cyst and we conduct a review of reported cases in the literature using PubMed database. RESULTS: From 1962 to September 2019, we gathered 91 articles with a total of 139 cases (ours included). There is a slightly female predominance and a bimodal age distribution. Acquired cysts are seen in 38.1% of patients. The most frequent symptom was pain, followed by motor deficit, sensitive deficits, and sphincter deficiencies. The mean time delay to diagnosis is 26.36 ± 53.29 months. The most common localization was in the lumbar area and one third of the tumors were intramedullary. A good outcome was achieved in most of the treated cases. CONCLUSIONS: To achieve a good outcome, an early recognition of this disease is essential. The management consists in most cases of surgical resection. Although recurrence is low, it can significantly alter the quality of life of our patients, and, therefore, gross total resection should be our goal.

Atypical Teratoid Rhabdoid Tumor of the Cauda Equina in a Child: Report of a Very Unusual Case.

Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive malignant primitive neoplasms that commonly occur in children younger than 2 years of age. The prognosis is generally dismal with a median survival time of <1 year. The majority of AT/RT occur in the posterior fossa and less frequently the supratentorium. Primary pediatric spinal AT/RT are exceedingly rare and only 15 cases have been reported to date. Here we report a very unusual case of primary spinal AT/RT extensively involving the spinal cord from T11 down to the cauda equina. In this patient, the tumor was highly aggressive and resulted in extensive dissemination into the nerve roots and paraspinal soft tissue rapidly resulting in the patient's death 1 month after diagnosis. to the best of our knowledge, this degree of involvement of the spine by a primary AT/RT has not been described before.

Development of a Novel Orthotopic Primary Human Chordoma Xenograft Model: A Relevant Support for Future Research on Chordoma.

Chordomas are slow-growing rare malignant neoplasms. The aim of this study was to establish a primary model of chordoma in the lumbosacral orthotopic area, to compare the growth rate to the subcutaneous site, and to show that this new graft site optimizes tumor growth and bony invasion. Eleven chordoma samples were transplanted subcutaneously in the flank and/or in contact with the lumbosacral region and grown into nude mice. Engraftment rate was significantly more successful in the lumbosacral environment compared with the flank at P0. Two xenografts from 2 patients showed bone invasion. One tumor was maintained through multiple rounds of serial transplantation, creating a model for study. Histological and immunostaining analysis confirmed that tumor grafts recapitulated the primary tumor from which they were derived, consisting of a myxoid chordoma expressing brachyury, cytokeratin AE1, EMA, and VEGF. Clear destruction of the bone by the tumor cells could be demonstrated. Molecular studies revealed PIK3CA and PTEN mutations involved in PI3K signaling pathway and most of the frequently reported chromosomal alterations. We present a novel orthotopic primary xenograft model of chordoma implanted for the first time in the lumbosacral area showing bone invasion, PIK3CA, and PTEN mutations that will facilitate preclinical studies.

Central nervous system hemangioblastomas in the elderly (over 65 years): Clinical characteristics and outcome analysis.

OBJECTIVES: Hemangioblastomas (HBs) in the elderly are very uncommon and have rarely been studied. This retrospective study aimed to identify clinical features, optimal treatment, surgical outcomes and long-term prognostic factors in these rare lesions. PATIENTS AND METHODS: We performed a retrospective analysis of HBs patients over 65 years old who underwent surgery from 2008 to 2018 at our department. Clinical data was retrospectively reviewed and statistically analyzed. RESULTS: Thirty-three elderly patients with a mean age of 68.76 years were included in this study. Cerebellum, brainstem, and spinal cord locations accounted for 72.7 %, 18.2 % and 9.1 %. Two patients (6.1 %) were diagnosed as von Hippel-Lindau (VHL) syndrome. After mean follow-up of 37.95 ± 22.12 months, clinical symptoms improved in 22 patients (67 %), unchanged in seven patients (21 %) and aggravated in 4 patients (12 %). Only 1(3 %) patient experienced local recurrence during follow-up. Univariate analysis showed tumor size (P = 0.044) and tumor characteristic (cystic or solid) (P = 0.034) were significantly related to long-term outcomes, while multiple logistic regression analysis depicted tumor characteristics were exclusively correlated with outcomes (P = 0.04). CONCLUSIONS: Our study suggests elderly hemangioblastomas may be different from their younger counterparts in that they often display solid configuration with large size and include more cerebellar tumors. HBs should be included in the differential diagnosis of elderly patients presenting with cerebellar mass. Despite many challenges involved, surgical removal of HBs in this age group is a safe procedure with acceptable risks. They may do not require as frequent follow-up as younger counterparts due to the low associations with VHL disease and tumor recurrence rate.

Intraoperative Neuromonitoring in Patients with Intramedullary Spinal Cord Tumor: A Systematic Review, Meta-Analysis, and Case Series.

BACKGROUND: Intramedullary spinal cord tumors (IMSCT) comprise the least common types of spinal neoplasms; surgery is mostly conducted with intraoperative neuromonitoring (IONM). However, although IONM is widely used to prevent neurologic damage and many single-center studies have been reported, the added value, in terms of overall sensitivity and specificity, of different monitoring techniques used in IMSCT surgery remains to be clearly defined. OBJECTIVE: To summarize and review the reported evidence on the use of IONM in IMSCT surgery, including our own case series (n = 75 patients). METHODS: We systematically searched the literature published from January 2000 to February 2018. Articles included patients with IMSCT who underwent surgery with neuromonitoring. We estimated the sensitivity, specificity, 95% confidence interval (CI), positive likelihood ratio, and negative likelihood ratio. RESULTS: Of 1385 eligible articles, 31 were included in the systematic review. Fifteen of these articles were used for a meta-analysis, complemented with our own case series. All neuromonitoring modalities showed acceptable but not optimal test characteristics. For the indications used in the different studies, the motor evoked potentials approach showed the highest sensitivity (0.838; 95% CI, 0.703-0.919) and the best specificity (0.829; 95% CI, 0.668-0.921) for detecting neuronal injury. In our own case series, the extent of resection was significantly smaller in the false-positive group than in the true-negative group (P = 0.045). CONCLUSIONS: IONM showed high but not perfect sensitivity and specificity. IONM prevents neurologic damage but can also limit the extent of tumor resection. Prospective studies will have to define the definitive value of IONM.

Primary B-cell Spinal Cord Lymphoma of the Cervical Spine.

Non-Hodgkin lymphomas are a heterogeneous group of tumours, with diffuse large B-cell lymphomas (DLBCL) being particularly common. Cases of DLBCLs developing in the central nervous system, especially in the spinal cord, are extremely rare and thus pose significant diagnostic and therapeutic problems, particularly for orthopaedists and neurologists since these are the specialists the patients first consult. The tumours often appear in immunosuppressed patients and standard chemotherapy is ineffective. This paper presents the case of a 44-year-old male with a lymphoma located in the spinal cord at the C7-Th1 level. The symptoms appeared suddenly and progressed rapidly, with dissociated sensory loss and limb paresis being the most pronounced. Imaging studies and the rapid symptom progression suggested neoplastic disease. An emergency surgical procedure was performed in order to decompress the spinal cord and thus limit neurological deficits. Tumour resection allowed for making a diagnosis. By four weeks after the surgery, the tumour had grown larger than before the procedure. Chemotherapy with MTX and Ara-C and intrathecal MTX resulted in full remission. Consolidation was achieved with radiotherapy. Currently, with the low incidence of such tumours, there are no standards of management in patients with DLBCLs of the CNS. The literature contains only a few case reports on successfully treated spinal cord DLBCLs.

Giant Dumbbell-Shaped Thoracic Schwannoma in an Elderly Patient Resected Through a Single-Stage Combined Laminectomy and Video-Assisted Thoracoscopy: Surgical Strategy and Technical Nuances.

BACKGROUND: Dumbbell-shaped schwannomas involving the spinal canal, the intervertebral foramen, and the thoracic cavity are rare lesions. Surgical treatment represents a challenge, and there is no consensus regarding ideal management. Two major surgical routes have been used: combined laminectomy and open thoracotomy or posterolateral extrapleural approach with wide bone removal. This report describes a relatively easy surgical strategy, combined laminectomy and thoracoscopy, which allows safe resection under an adequate view with low risk of spinal instability, pain, or respiratory problems. CASE DESCRIPTION: A 74-year-old man presented with rapidly progressing motor impairment caused by a dumbbell-shaped, 65-mm, Eden type III lesion at the T5 level. Magnetic resonance imaging showed an intraspinal-extradural mass extending into the chest cavity and causing severe spinal cord compression. The patient underwent single-stage surgery performed by a neurosurgical and thoracic team. The extradural and foraminal tumor components were first removed through a 1-level laminectomy with foraminotomy and without facetectomy. Subsequently, video-assisted thoracic surgery was performed to approach the anterior paraspinal component. Total tumor removal, confirmed with postoperative magnetic resonance imaging, was achieved. Pathologic diagnosis was schwannoma. The postoperative course was uneventful. The patient's neurologic deficits resolved, and he experienced minimal pain after the operation. CONCLUSIONS: A single-stage operation using combined laminectomy and video-assisted thoracic surgery is a safe and efficacious strategy for achieving total removal of dumbbell-shaped thoracic schwannomas, even in cases involving giant lesions and elderly patients.

Placode rotation in transitional lumbosacral lipomas: are there implications for origin and mechanism of deterioration?

PURPOSE: Rotation of the lipoma-neural placode has been noted in transitional lumbosacral lipomas. The purpose of this study was to confirm this rotation; that this rotation occurs with a preference to the left, and correlates with clinical symptoms. In addition, this study tests the hypothesis that this rotation occurs through local mechanical forces rather than intrinsic congenital malformation. METHODS: Lipomas were classified as per the Chapman classification. Degree of rotation of the placode from the coronal plane was recorded along with the presence of herniation outside of the vertebral canal. Abnormalities on urodynamic testing were recorded, along with neuro-orthopaedic signs picked up on formal neuro-physiotherapy assessment. RESULTS: Placode rotation occurs more frequently in the transitional group. Regardless of lipoma classification, rotation was much more common to the left. Furthermore, when lateralisation of symptoms was present, this strongly correlated with the direct of rotation. There was no difference in rotation of the placode whether it was within (lipomyelocoele) or without the vertebral canal (lipomyelomeningocoele). CONCLUSIONS: Placode rotation is a feature of transitional lumbosacral lipomas and may account for the increase in symptoms amongst this subgroup. Herniation of the placode outside the vertebral canal does not increase the risk of rotation suggesting a congenital cause for this finding rather than a purely mechanical explanation.

Intraoperative identification of the corticospinal tract and dorsal column of the spinal cord by electrical stimulation.

OBJECTIVES: Anatomical identification of the corticospinal tract (CT) and the dorsal column (DC) of the exposed spinal cord is difficult when anatomical landmarks are distorted by tumour growth. Neurophysiological identification is complicated by the fact that direct stimulation of the DC may result in muscle motor responses due to the centrally activated H-reflex. This study aims to provide a technique for intraoperative neurophysiological differentiation between CT and DC in the exposed spinal cord. METHODS: Recordings were obtained from 32 consecutive patients undergoing spinal cord tumour surgery from July 2015 to March 2017. A double train stimulation paradigm with an intertrain interval of 60 ms was devised with recording of responses from limb muscles. RESULTS: In non-spastic patients (55% of cohort) an identical second response was noted following the first CT response, but the second response was absent after DC stimulation. In patients with pre-existing spasticity (45%), CT stimulation again resulted in two identical responses, whereas DC stimulation generated a second response that differed substantially from the first one. The recovery times of interneurons in the spinal cord grey matter were much shorter for the CT than those for the DC. Therefore, when a second stimulus train was applied 60 ms after the first, the CT-fibre interneurons had already recovered ready to generate a second response, whereas the DC interneurons were still in the refractory period. CONCLUSIONS: Mapping of the spinal cord using double train stimulation allows neurophysiological distinction of CT from DC pathways during spinal cord surgery in patients with and without pre-existing spasticity.

False-Positive and False-Negative Results of Motor Evoked Potential Monitoring During Surgery for Intramedullary Spinal Cord Tumors.

BACKGROUND: Motor evoked potential (MEP) recording is used as a method to monitor integrity of the motor system during surgery for intramedullary tumors (IMTs). Reliable sensitivity of the monitoring in predicting functional deterioration has been reported. However, we observed false positives and false negatives in our experience of 250 surgeries of IMTs. OBJECTIVE: To delineate specificity and sensitivity of MEP monitoring and to elucidate its limitations and usefulness. METHODS: From 2008 to 2011, 58 patients underwent 62 surgeries for IMTs. MEP monitoring was performed in 59 operations using transcranial electrical stimulation. Correlation with changes in muscle strength and locomotion was analyzed. A group undergoing clipping for unruptured aneurysms was compared for elicitation of MEP. RESULTS: Of 212 muscles monitored in the 59 operations, MEP was recorded in 150 (71%). Positive MEP warnings, defined as amplitude decrease below 20% of the initial level, occurred in 37 muscles, but 22 of these (59%) did not have postoperative weakness (false positive). Positive predictive value was limited to 0.41. Of 113 muscles with no MEP warnings, 8 muscles developed postoperative weakness (false negative, 7%). Negative predictive value was 0.93. MEP responses were not elicited in 58 muscles (27%). By contrast, during clipping for unruptured aneurysms, MEP was recorded in 216 of 222 muscles (96%). CONCLUSION: MEP monitoring has a limitation in predicting postoperative weakness in surgery for IMTs. False-positive and false-negative indices were abundant, with sensitivity and specificity of 0.65 and 0.83 in predicting postoperative weakness.