Sven O. Eicker

Prospective, Randomized, Open-Label Phase II Trial on Concomitant Intraventricular Fibrinolysis and Low-Frequency Rotation After Severe Subarachnoid Hemorrhage

Background and Purpose— The goal of this randomized, open-label phase II study was to investigate the effect of concomitant low-frequency head-motion therapy and intraventricular fibrinolysis in patients after surgical or endovascular treatment for aneurysmal subarachnoid hemorrhage. Methods— Sixty patients experiencing subarachnoid hemorrhage were randomized into treatment with intraventricular application of recombinant tissue-type plasminogen activator and lateral rotational therapy (experimental) or treatment as usual (control). The primary end point was defined as functional outcome, measured by Glasgow Outcome Scale at discharge and at 3-month follow-up. Clot clearance rate, radiographic features of delayed cerebral ischemia, and posthemorrhagic hydrocephalus were defined as secondary end points. Results— The majority of patients (78.3%) experienced severe subarachnoid hemorrhage. Although there was a higher incidence of subgaleal hematomas in the experimental group, there was no difference in the incidence of adverse or severe adverse events between the 2 groups. Despite significantly higher clot clearance rates, there was no beneficial effect on the incidence of delayed cerebral ischemia and poor functional outcome, as well as posthemorrhagic hydrocephalus after experimental treatment. Conclusions— Despite the ineffectiveness on reduction of delayed cerebral ischemia or poor functional outcome, intraventricular fibrinolysis and kinetic therapy seems to be a safe and effective concept for therapeutic reduction of subarachnoid clot in a patient collective experiencing predominately severe subarachnoid hemorrhage. Therefore, future studies should investigate this treatment in a larger patient collective with a lower degree of primary brain injury and until full clot clearance on serial imaging. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ICRCTN13230264.

Prognostic Value of 18F-FDG PET in Monosegmental Stenosis and Myelopathy of the Cervical Spinal Cord

MRI offers perfect visualization of spondylotic stenosis of the cervical spine, but morphologic imaging does not correlate with clinical symptoms and postoperative recovery after decompression surgery. In this prospective study, we investigated the role of 18F-FDG PET in patients with degenerative stenosis of the cervical spinal cord in relation to postsurgical outcome. Methods: Twenty patients with monosegmental spondylotic stenosis of the middle cervical spine (C3/C4 or C4/C5) showing intramedullary hyperintensity on T2-weighted MRI and clinical symptoms of myelopathy (myelopathic patients) were investigated by 18F-FDG PET. Maximum standardized uptake values (SUVmax) were measured at all levels of the cervical spine (C1–C7). Decompression surgery and anterior cervical fusion were performed on all patients, and clinical status (Japanese Orthopedic Association [JOA] score) was assessed before and 6 mo after surgery. The 18F-FDG data of 10 individuals without cervical spine pathology were used as a reference (controls). Results: The myelopathic patients showed a significant decrease in 18F-FDG uptake in the area of the lower cervical cord, compared with the control group (C7 SUVmax, 1.49 ± 0.18 vs. 1.71 ± 0.27, P = 0.01). Ten myelopathic patients exhibited focally increased 18F-FDG uptake at the level of the stenosis (SUVmax, 2.27 ± 0.41 vs. 1.75 ± 0.22, P = 0.002). The remaining 10 patients showed inconspicuous 18F-FDG uptake at the area of the stenosis. Postoperatively, the patients with focally increased 18F-FDG accumulation at the level of stenosis showed good clinical recovery and a significant improvement in JOA scores (13.6 ± 2.3 vs. 9.5 ± 2.5, P = 0.001), whereas no significant improvement was observed in the remaining patients (JOA score, 12.0 ± 2.4 vs. 11.6 ± 2.5, not statistically significant). Multiple regression analysis identified the presence of focally increased 18F-FDG uptake at the level of the stenosis as an independent predictor of postoperative outcome (P = 0.002). Conclusion: The results suggest that regional changes in 18F-FDG uptake have prognostic significance in compression-induced cervical myelopathy that may be helpful in decisions on the timing of surgery.

Intracranial carotid artery stent placement causes delayed severe intracranial hemorrhage in a patient with moyamoya disease

Background Moyamoya disease (MMD) is a rare cerebrovascular disease usually characterized by progressive bilateral distal internal carotid artery stenosis or occlusion and its consequences. Direct (ie, extracranial–intracranial bypass) or indirect cerebral revascularization procedures are the most established and effective treatment strategies for MMD. The case history is presented of a patient with MMD with delayed severe intracranial and subarachnoid hemorrhage following intracranial carotid artery stent placement. Clinical presentation An 18-year-old women presented with a history of seizures, recurrent episodes of transient right hemiparesis and aphasia. Cerebral catheter angiography and perfusion CT scan with azetozaolamide challenge confirmed impaired left hemispheric perfusion due to severe bilateral carotid artery stenosis combined with pathological collaterals, consistent with moyamoya disease. Endovascular stenting of the left supraclinoidal internal cerebral artery was performed uneventfully. Five hours after treatment the patient presented with sudden headache, nausea and speech disorders and a CT scan revealed intracerebral and subarachnoid hemorrhage. Due to further rapid clinical deterioration, surgical removal of the hematoma and decompression were required. The patient’s poor neurological outcome did not improve during the 2-year follow-up period. Conclusion This case report illustrates a severe intracerebral and subarachnoid hemorrhage following intracranial stenting of the internal carotid artery in a young patient with MMD. Potentially this complication could be attributed to high perfusion pressure breakthrough phenomenon, a known complication after cerebral high-flow bypass surgery. The role of intracranial stenting, despite established revascularization procedures in patients with MMD, therefore remains highly questionable.

DOSE‐RELATED EFFICACY OF A CONTINUOUS INTRACISTERNAL NIMODIPINE TREATMENT ON CEREBRAL VASOSPASM IN THE RAT DOUBLE SUBARACHNOID HEMORRHAGE MODEL

OBJECTIVEIntracisternal continuous therapy is a concept in the treatment of cerebral vasospasm after subarachnoid hemorrhage. The purpose of the current study was to investigate the effect of intracisternal nimodipine after induced vasospasm. METHODSSixty-five male Wistar rats were randomized into 4 groups: the control sham-operated group, the control subarachnoid hemorrhage-only group, and the treatment groups receiving 5 or 10 μL/hour of intracisternal nimodipine continuously for 5 days via subcutaneously implanted Alzet osmotic pumps (Durect Corp., Cupertino, CA). Vasospasm was analyzed 5 days later by means of digital subtraction angiography. Morphological examination of the brain parenchyma was performed using Nissl-staining, c-Fos immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling. RESULTSDetailed analysis of the digital subtraction angiography was possible for 31 animals. Significant angiographic vasospasm was induced in the double hemorrhage-only group compared with the sham-operated group (P = 0.002). Among the 4 groups, there were statistically significant differences of the arterial vessel caliber as measured by digital subtraction angiography (P = 0.001, Kruskal-Wallis test). The treatment group receiving 5 μL/hour of nimodipine and the control sham-operated group demonstrated the largest intracranial artery diameters with a significant difference between control subarachnoid hemorrhage-only group and the treatment group receiving 10 μL/hour of nimodipine (P = 0.0328, Wilcoxon rank-sum test). Variation in vessel calibers, however, did not result in different brain tissue alterations, even when using sensitive markers for the induction of the stress response or apoptosis. CONCLUSIONIntracisternal nimodipine lavage with 5 μL/hour, but not with 10 μL/hour leads to significant arterial relaxation. Further research is needed to elucidate the underlying cause of the decreasing nimodipine effect at higher dosage.

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.

Hypermetabolism in 18F-FDG PET Predicts Favorable Outcome Following Decompressive Surgery in Patients with Degenerative Cervical Myelopathy

The aim of this study was to prospectively assess the regional changes of glucose metabolism of the cervical spinal cord in patients with degenerative cervical spine stenosis and symptomatic cervical myelopathy after decompressive surgery using 18F-FDG PET. Methods: Twenty patients with symptomatic degenerative monosegmental cervical stenosis with neuroradiologic signs of spinal cord compression underwent decompressive surgery. The clinical course using a functional status score (Japanese Orthopedic Association [JOA] score), 18F-FDG uptake, and MR imaging were assessed before and at follow-up 12 mo after surgery. Pre- and postoperative changes of 18F-FDG PET were correlated to the patients’ clinical outcome. Results: Ten patients demonstrated preoperatively a focally increased 18F-FDG uptake at the level of the stenosis. At follow-up, the uptake declined significantly (P = 0.008), and a significant improvement of JOA scores (P < 0.001) could be observed. The remaining 10 patients were characterized preoperatively by an inconspicuous glucose uptake at the level of cord compression in combination with a poststenotic decrease of 18F-FDG uptake. At follow-up, both JOA scores and 18F-FDG uptake changed insignificantly. Conclusion: Focal glucose hypermetabolism at the level of cervical spinal cord compression may predict an improved outcome after surgical decompression. Thus, this finding on 18F-FDG PET suggests a functional damage in a reversible phase of cervical myelopathy.

Transtubular microsurgical approach to treating extraforaminal lumbar disc herniations

OBJECT Approaches to treating extraforaminal lumbar disc herniations can be challenging due to the unique anatomy and the need to prevent spinal instability. Numerous approaches, including conventional midline, paramedian, minimally invasive, and full endoscopic approaches, have been described. The purposes of this study were to point out the outcome and clinical advantages of a transtubular microsurgical approach and to describe and illustrate this technique. METHODS Between 2009 and 2012, a series of 51 patients underwent a minimally invasive dilative transtubular microsurgical approach for the treatment of extraforaminal lumbar disc herniations. All patients were clinically evaluated using the visual analog scale (VAS) and Oswestry Disability Index preoperatively and 6 months postoperatively. RESULTS Both pain scores and functional status showed significant improvement after surgery (p < 0.001): radicular pain decreased from VAS score of 7.9 to one of 1.3, lower back pain from VAS score of 2.4 to 1.4, and the Oswestry Disability Index from 42.0 to 12.3. Subgroup analyses revealed no differences in outcome regarding obesity or timing of surgery (early vs late intervention). Highly significant was the correlation between preoperative radicular pain activity and timing of surgical intervention (p < 0.001). CONCLUSIONS The dilative transtubular microsurgical approach combines the advantages of the conventional open muscle-splitting approach and the endoscopic approach. The technique is easy to use with a steep learning curve. Less muscle trauma and the absence of bony resection prevent facet pain and instability, thereby contributing to a rapid recovery. Patients in this series improved excellently in the short-term follow-up.

Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.

Background and Purpose To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH). Methods 70 male Wistar rats were categorized into three groups: 1) sham operated animals (control), 2) animals with SAH only (control) and the 3) treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40%) of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA). Histological analysis of frozen sections was performed using H&E-staining as well as Iba1 and MAP2 immunohistochemistry. Results DSA images were sufficient for assessment in 42 animals. Severe angiographic vasospasm was present in group 2 (SAH only), as compared to the sham operated group (p<0.001). Only animals within group 3 and the highest nimodipine microparticles concentration (40%) as well as group 1 (sham) demonstrated the largest intracranial artery diameters. Variation in vessel calibers, however, did not result in differences in Iba-1 or MAP2 expression, i.e. in histological findings for secondary brain injury. Conclusions Local delivery of high-dose nimodipine prolonged-release microparticles at high concentration resulted in significant reduction in angiographic vasospasm after experimental SAH and with no histological signs for matrix toxicity.

Custom-tailored minimally invasive partial C2-corpectomy for ventrally located intramedullary cavernous malformation

Approaches to ventrally located intramedullary lesions of the upper cervical spine can be extremely challenging. We present a custom-tailored, minimally invasive anterior approach to a ventrally located, intramedullary cavernous hemangioma with partial lateral corpectomy of C2, complete resection of the lesion and subsequent reconstruction. A 20-year-old woman presented with the history of progressive numbness of the left upper and lower extremities and some episodes of severe headaches was referred to magnetic resonance imaging: Here, an intramedullary lesion with typical radiological features for a cavernous malformation at the ventral surface of the spinal cord at the C2 level was detected. The surgical procedure was performed under general anesthesia and electrophysiological monitoring (somatosensory-evoked potentials (SEP), muscle motor-evoked potentials (MEP), and D-wave recording). Complete resection of the cavernous malformation was achieved and reconstruction of the cervical spine was performed using a custom-tailored cage. Intraoperative neuromonitoring during resection, revealed a transient MEP loss, but unchanged D-wave and SEP recordings indicated unchanged neurological outcome. Early clinical follow-up of the patient revealed no new neurological deficits. At 3-month follow-up, there was some improvement of the sensory function. This custom-tailored minimally invasive anterior approach to a ventrally located intramedullary cavernous malformation with partial C2-corpectomy describes a possible and successful approach to ventrally located intramedullary lesions of the upper cervical spinal cord. Additionally, the hereby-described approach is not related to cervical instability.

Primary spinal marginal zone lymphoma: case report and review of the literature.

BACKGROUND AND IMPORTANCE Marginal zone lymphoma (MZL) describes a heterogeneous group of indolent B-cell lymphomas. The World Health Organization recognizes 3 types of MZLs: splenic MZL, nodal MZL, and extranodal MZL of mucosa-associated lymphoid tissue. There is no consensus on the optimal adjuvant treatment modalities for intracranial primary MZLs. To date, no case of spinal primary MZL has been reported. CLINICAL PRESENTATION We present the first case of spinal MZL diagnosed in a 65-year-old man with progressive paraparesis. He underwent surgical removal of the main spinal tumor mass, which extended epidurally from vertebral body T3 to T7. Surgery was followed by 10 sessions of local irradiation for a total dose of 31 Gy. On long-term follow-up in 2010, the patient was in good health without any signs of residual or recurrent disease. Twenty-seven publications reporting on 61 cases of intracranial primary MZL were identified and reviewed. In the majority of cases of marginal zone B-cell lymphoma, adjuvant radiotherapy was used, with some combining radiotherapy and chemotherapy after surgical removal of the bulk of the main tumor. Long-term follow-up in most patients showed no evidence of disease and clinical well-being years after the initial diagnosis. CONCLUSION Chemotherapy and/or radiation have been used in larger case series. Although there is no defined treatment guideline for this rare disease entity, our review of the literature suggests a favorable prognosis when combining surgical and adjuvant radiotherapy approaches.