Klaus Christian Mende

Intramedullary spinal cord metastases: an increasingly common diagnosis

OBJECT Intramedullary spinal cord metastases (ISCM) represent a small proportion of intramedullary tumors. However, with the lifespans of patients with malignant tumors increasing, incidents of ISCM are on the rise. Due to threateningly severe disabilities in patients, accompanied by limited life expectancy, every attempt should be made to treat these tumors the same way as metastases elsewhere in the CNS, with the goal of complete removal of the ISCM and preservation of neurological functions. The object of this study is to retrospectively analyze the experiences of 22 patients who were surgically treated for ISCM over a 22-year period. METHODS Hospital charts of 22 patients, who were surgically treated for ISCM between 1992 and 2014, were reviewed retrospectively. Demographic data, histopathological diagnoses of primary cancer, chronological sequence of the disease, and neurological status using the simplified McCormick functional classification were collected and reanalyzed. RESULTS The most frequent histology was metastasis of lung cancer, followed by brain and breast cancers. The time span from primary cancer diagnosis to the development of symptomatic spinal metastases ranged from 0 to 285 months, with a mean interval of 38 months. The leading presenting sign was dysesthesia (77% of the population), followed by paresis (68%). Only 5 patients (23%) showed urinary retention. Initial performance status represented by the McCormick Scale was on average 2.47. Total or near-total removal was achieved in 87% of cases. Compared with the clinical status 1-2 days after surgery, there was an improvement in the McCormick Scale grade at the last follow-up from 2.47 to 2.12 (p = 0.009). Likewise, an improvement was detected when comparing the preoperative status with the last follow-up (from 2.45 to 2.12; p = 0.029). The mean survival time after surgery was 11.6 months. CONCLUSIONS These results suggest that surgery for intramedullary metastases-with all of the challenges of a rare and potentially risky procedure-can be beneficial to patients with advanced stages of cancer. Surgery can be performed with minimal new morbidity and results in maintaining neurological performance status.

Minimally invasive approach for small ventrally located intradural lesions of the craniovertebral junction

OBJECT The surgical management of lesions ventral to the neuraxis at the level of the craniovertebral junction (CVJ) and upper cervical spine is challenging. Here, the authors describe a minimally invasive dorsal approach for small ventrally located intradural lesions at the CVJ as an alternative for the more extensive classic transoral approach or variants of suboccipital approaches. METHODS Between 2012 and 2014, 6 symptomatic patients with a small lesion of the ventral aspect at the CVJ level were treated using a minimally invasive dorsal approach at the University Medical Center in Hamburg-Eppendorf, Germany. The anatomical distance between the posterior atlantooccipital membrane and the posterior atlantoaxial ligament, as determined by CT images, was assessed in the treated patients and in 100 untreated persons. RESULTS The authors treated 6 patients (mean age 54.7 years) who had a clinical presentation of mild neurological symptoms that disappeared after resection. Minimally invasive surgical dorsal access was achieved by using tubular systems and using the natural space between the occiput (C-0) and C-1, and in 1 case between C-1 and C-2, without having to remove bony structures. The postoperative course in each of the 6 patients was uneventful. The neuropatho-logical findings confirmed a meningotheliomatous meningioma (WHO Grade I) in 5 cases and an extramedullary cavernous hemangioma in 1 case. MRI confirmed complete resection of all the lesions. The atlantooccipital distances ranged from 3 to 17 mm (mean 8.98 mm) in the supine neutral position, and the atlantoaxial distances ranged from 5 to 17 mm (mean 10.56 mm). There were no significant differences between women and men (atlantooccipital p = 0.14; atlantoaxial p = 0.72). CONCLUSIONS The results of this study demonstrate that the minimally invasive dorsal approach using the space between C-0 and C-1 or C-1 and C-2 provides direct and sufficient exposure for the safe surgical resection of small ventrally located intradural lesions at the CVJ level while reducing the necessity for musculoskeletal preparation to a minimum.

Keyhole approaches to intradural pathologies

OBJECTIVE Spinal tumors account for 2%-4% of all tumors of the central nervous system and can be intramedullary, intradural extramedullary, or extradural. In the past, wide approaches were used to obtain safe access to these tumors, as complete resection is the goal in treating most tumor entities. To reduce surgical complications due to large skin incisions and destabilizing laminectomies, minimally invasive approaches were established. In this study, the authors share their experience with mini-open approaches to intradural tumor pathologies. METHODS The authors retrospectively reviewed cases involving patients with intramedullary and intradural extramedullary lesions treated between 2009 and 2016. They present their surgical mini-open approach to the spinal cord as well as unique characteristics, key steps, and postsurgical complications for specific tumor subgroups (meningioma, neuroma, and intramedullary tumors). RESULTS A total of 245 intradural tumors were surgically treated during the study period. Of these lesions, 151 were intradural extramedullary meningiomas (n = 79) or neuromas (n = 72). Nine (12.5%) of the neuromas were dumbbell neuromas. Ninety-four tumors were intramedullary. The mean age of the patients was 51.4 years, and 53.9% were female. The mean duration of follow-up was 46.0 months. All meningiomas and neuromas could be resected using a mini-open keyhole approach, but only 5.3% of the intramedullary lesions could be accessed using this technique. Of the 94 patients with intramedullary tumors, 76.6% required a laminotomy, 7.4% required a hemilaminectomy, and 10.6% required a 2-level laminectomy. Only 2 of the patients with intramedullary tumors needed stabilization for progressive cervical kyphosis during follow-up. None of the other patients developed spinal instability after undergoing surgery via the mini-open (keyhole/interlaminar) approach. There were significantly more surgery-associated complications in the large exposure group than in the patients treated with the mini-open approach (19.1% vs 9.6%, p < 0.01). CONCLUSIONS Intradural extramedullary and in selected cases intramedullary pathologies may safely be resected using a mini-open interlaminar approach. Avoiding laminectomy, laminotomy, and even hemilaminectomy preserves spinal stability and significantly reduces comorbidities, while still allowing for complete resection of these tumors.

Validation of the modified Graeb score in aneurysmal subarachnoid hemorrhage

BackgroundIntraventricular hemorrhage (IVH) in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is a known negative predictor. Scoring systems like Fisher, Le Roux, and original Graeb score (oGS) are established to quantify the volume of IVH. The aim of this study was to evaluate the validity of the recently introduced modified Graeb score (mGS) in patients with aSAH.MethodsA retrospective analysis of the validity of the oGS and mGS in 257 aSAH patients was performed to assess and compare the predictive value of hospital mortality, development of CHC, and early functional outcome.ResultsIn univariate analysis, an increase in either the oGS or mGS was associated with a higher risk for hospital mortality, development of CHC, and poor early functional outcome. The correlation of the oGS and mGS was excellent using Pearson’s product–moment (r = 0.918; p < 0.001). The predictive value of the oGS was superior to the predictive value of the mGS using receiver operating characteristics and corresponding area under the curve value as there was no statistical significant differences between the scores.ConclusionsOur study confirms the validity of the recently introduced mGS to quantify the volume of IVH and extends its value in aSAH. However, the mGS offers no additional predictive value for hospital mortality, development of CHC, and poor early functional outcome in patients with aSAH patients compared to the less complex oGS.

Immunophenotyping of Newly Diagnosed and Recurrent Glioblastoma Defines Distinct Immune Exhaustion Profiles in Peripheral and Tumor-infiltrating Lymphocytes

Purpose: Immunotherapeutic treatment strategies for glioblastoma (GBM) are under investigation in clinical trials. However, our understanding of the immune phenotype of GBM-infiltrating T cells (tumor-infiltrating lymphocytes; TILs) and changes during disease progression is limited. Deeper insight is urgently needed to therapeutically overcome tumor-induced immune exhaustion. Experimental Design: We used flow cytometry and cytokine assays to profile TILs and peripheral blood lymphocytes (PBLs) from patients with GBM, comparing newly diagnosed or recurrent GBM to long-term survivors (LTS) and healthy donors. TCR sequencing was performed on paired samples of newly diagnosed and recurrent GBM. Results: We identified a clear immune signature of exhaustion and clonal restriction in the TILs of patients with GBM. Exhaustion of CD8+ TILs was defined by an increased prevalence of PD-1+, CD39+, Tim-3+, CD45RO+, HLA-DR+ marker expression, and exhibition of an effector-/transitional memory differentiation phenotype, whereas KLRG1 and CD57 were underrepresented. Immune signatures were similar in primary and recurrent tumors; however, restricted TCR repertoire clonality and a more activated memory phenotype were observed in TILs from recurrent tumors. Moreover, a reduced cytokine response to PHA stimulation in the blood compartment indicates a dysfunctional peripheral T-cell response in patients with GBM. LTS displayed a distinct profile, with abundant naïve and less exhausted CD8+ T cells. Conclusions: TILs and PBLs exhibit contrasting immune profiles, with a distinct exhaustion signature present in TILs. While the exhaustion profiles of primary and recurrent GBM are comparable, TCR sequencing demonstrated a contracted repertoire in recurrent GBM, concomitant with an increased frequency of activated memory T cells in recurrent tumors. Clin Cancer Res; 24(17); 4187–200. ©2018 AACR. See related commentary by Jackson and Lim, p. 4059

Impact of the surgical strategy on the incidence of C5 nerve root palsy in decompressive cervical surgery

Objective Our aim was to identify the impact of different surgical strategies on the incidence of C5 palsy. Background Degenerative cervical spinal stenosis is a steadily increasing morbidity in the ageing population. Postoperative C5 nerve root palsy is a common complication with severe impact on the patients´ quality of life. Methods We identified 1708 consecutive patients who underwent cervical decompression surgery due to degenerative changes. The incidence of C5 palsy and surgical parameters including type and level of surgery were recorded to identify predictors for C5 nerve palsy. Results The overall C5 palsy rate was 4.8%, with 18.3% of cases being bilateral. For ACDF alone the palsy rate was low (1.13%), compared to 14.0% of C5 palsy rate after corpectomy. The risk increased with extension of the procedures. Hybrid constructs with corpectomy plus ACDF at C3-6 showed significantly lower rates of C5 palsy (10.7%) than corpectomy of two vertebrae (p = 0.005). Multiple regression analysis identified corpectomy of C4 or C5 as a significant predictor. We observed a lower overall incidence for ventral (4.3%) compared to dorsal (10.9%) approaches (p<0.001). When imaging detected a postoperative shift of the spinal cord at index segment C4/5, palsy rate increased significantly (33.3% vs. 12.5%, p = 0.034). Conclusions Extended surgical strategies, such as dorsal laminectomies, multilevel corpectomies and procedures with extensive spinal cord shift were shown to display a high risk of C5 palsy. The use of extended procedures should therefore be employed cautiously. Switching to combined surgical methods like ACDF plus corpectomy can reduce the rate of C5 palsy.

Pituicytoma-An outlook on possible targeted therapies

Pituicytoma is a rare neoplasm of the sella region. Tumor resection is the primary treatment option, but remains subtotal due to excessive bleeding in many cases. The search for alternative or additional treatment regimens is necessary.

Intraocular pressure during neurosurgical procedures in context of head position and loss of cerebrospinal fluid

OBJECTIVEPerioperative visual loss (POVL) is a rare but serious complication in surgical disciplines, especially in spine surgery. The exact pathophysiology of POVL remains unclear, but elevated intraocular pressure (IOP) is known to be part of it. As POVL is rarely described in patients undergoing intracranial or intradural surgery, the aim of this study was to investigate the course of IOP during neurosurgical procedures with opening of the dura mater and loss of CSF.METHODSIn this prospective, controlled trial, 64 patients fell into one of 4 groups of 16 patients each. Group A included patients undergoing spine surgery in the prone position, group B patients had intracranial procedures in the prone position, and group C patients were treated for intracranial pathologies in a modified lateral position with the head rotated. In groups A-C, the dura was opened during surgery. Group D patients underwent spine surgeries in the prone position with an intact dura. IOP was measured continuously pre-, peri-, and postoperatively.RESULTSIn all groups, IOP decreased after induction of anesthesia and increased time dependently after final positioning for the operation. The maximum IOP in group A prior to opening of the dura was 28.6 ± 6.2 mm Hg and decreased to 23.44 ± 4.9 mm Hg directly after dura opening (p < 0.0007). This effect lasted for 30 minutes (23.5 ± 5.6 mm Hg, p = 0.0028); after 60 minutes IOP slowly increased again (24.5 ± 6.3 mm Hg, p = 0.15). In group B, the last measured IOP before CSF loss was 28.1 ± 5.0 mm Hg and decreased to 23.5 ± 6.1 mm Hg (p = 0.0039) after dura opening. A significant IOP decrease in group B lasted at 30 minutes (23.6 ± 6.0 mm Hg, p = 0.0039) and 60 minutes (23.7 ± 6.0 mm Hg, p = 0.0189). In group C, only the lower eye showed a decrease in IOP up to 60 minutes after loss of CSF (opening of dura, p = 0.0007; 30 minutes, p = 0.0477; 60 minutes, p = 0.0243). In group D (control group), IOP remained stable throughout the operation after the patient was prone.CONCLUSIONSThis study is the first to demonstrate that opening of the dura with loss of CSF during neurosurgical procedures results in a decrease in IOP. This might explain why POVL predominantly occurs in spinal but rarely in intracranial procedures, offers new insight to the pathophysiology of POVL, and provides the basis for further research and treatment of POVL.German Clinical Trials Register (DRKS) no.: DRKS00007590 (drks.de).

Somatosensory evoked potentials in patients with high-grade aneurysmal subarachnoid hemorrhage

OBJECTIVE The aim of this prospective study was to investigate the value of somatosensory evoked potentials (SEPs) in predicting outcome in patients with high-grade aneurysmal subarachnoid hemorrhage (SAH). METHODS Between January 2013 and January 2015, 48 patients with high-grade SAH (Hunt and Hess Grade III, IV, or V) who were admitted within 3 days after hemorrhage were enrolled in the study. Right and left median and tibial nerve SEPs were recorded on Day 3 after hemorrhage and recorded again 2 weeks later. Glasgow Outcome Scale (GOS) scores were determined 6 months after hemorrhage and dichotomized as poor (Scores 1-3) or good (Scores 4-5). Results of SEP measurements were dichotomized (present or missing cortical responses or normal or prolonged latencies) for each nerve and side. These variables were summed and tested using logistic regression and a receiver operating characteristic curve to assess the value of SEPs in predicting long-term outcome. RESULTS At the 6-month follow-up visit, 29 (60.4%) patients had a good outcome, and 19 (39.6%) had a poor outcome. The first SEP measurement did not correlate with clinical outcome (area under the curve [AUC] 0.69, p = 0.52). At the second measurement of median nerve SEPs, all patients with a good outcome had cortical responses present bilaterally, and none of them had bilateral prolonged latencies (p = 0.014 and 0.003, respectively). In tibial nerve SEPs, 7.7% of the patients with a good GOS score had one or more missing cortical responses, and bilateral prolonged latencies were found in 23% (p = 0.001 and 0.034, respectively). The second measurement correlated with the outcome regarding each of the median and tibial nerve SEPs and the combination of both (AUC 0.75 [p = 0.010], 0.793 [p = 0.003], and 0.81 [p = 0.001], respectively). CONCLUSIONS Early SEP measurement after SAH did not correlate with clinical outcome, but measurement of median and tibial nerve SEPs 2 weeks after a hemorrhage did predict long-term outcome in patients with high-grade SAH.