Intraoperative Neuromonitoring in Patients with Intradural Extramedullary Spinal Cord Tumor: A Single-Center Case Series.

BACKGROUND: Intradural extramedullary spinal cord tumors (ID-EMSCT) make up 40% of all spinal neoplasms. Resection of these tumors is mostly conducted using intraoperative neuromonitoring (IONM). However, the literature shows heterogenous data on its added value for ID-EMSCT. The aim of this study is to define sensitivity and specificity of IONM in ID-EMSCT resection and to study possible correlations between preoperative, intraoperative, and postoperative variables and neurologic outcomes after ID-EMSCT resection. METHODS: Data of patients undergoing ID-EMSCT surgeries with IONM from January 2012 until July 2019 were examined. Using neurologic status 6 weeks and 1 year postoperatively, sensitivity and specificity for IONM were calculated. IONM test results and neurologic outcomes were paired to preoperative, intraoperative, and postoperative parameters. RESULTS: Data of 78 patients were analyzed. 6 weeks postoperatively, 14.10% of patients had worse neurologic status, decreasing to 9.84% 1 year postoperatively. Multimodal IONM showed a sensitivity of 0.73 (95% confidence interval [CI], 0.39-0.94) and a specificity of 0.78 (95% CI, 0.66-0.87) after 6 weeks, and a sensitivity of 1.00 (95% CI, 0.54-1.00) and a specificity of 0.71 (95% CI, 0.57-0.82) after 1 year. CONCLUSIONS: IONM yielded high to perfect sensitivity and high specificity. However, IONM signals did not always determine the extent of resection, and false-positive results did not always result in incomplete tumor resections, because of surgeons overruling IONM. Therefore, IONM cannot fully replace clinical judgment and other perioperative information.

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.

Clinical, electrophysiological, and cutaneous innervation changes in patients with bortezomib-induced peripheral neuropathy reveal insight into mechanisms of neuropathic pain.

Bortezomib is a mainstay of therapy for multiple myeloma, frequently complicated by painful neuropathy. The objective of this study was to describe clinical, electrophysiological, and pathological changes of bortezomib-induced peripheral neuropathy (BiPN) in detail and to correlate pathological changes with pain descriptors. Clinical data, nerve conduction studies, and lower leg skin biopsies were collected from 22 BiPN patients. Skin sections were immunostained using anti-protein gene product 9.5 (PGP9.5) and calcitonin gene-related peptide (CGRP) antibodies. Cumulative bortezomib dose and clinical assessment scales indicated light-moderate sensory neuropathy. Pain intensity >4 (numerical rating scale) was present in 77% of the patients. Median pain intensity and overall McGill Pain Questionnaire (MPQ) sum scores indicated moderate to severe neuropathic pain. Sural nerve sensory nerve action potentials were abnormal in 86%, while intraepidermal nerve fiber densities of PGP9.5 and CGRP were not significantly different from healthy controls. However, subepidermal nerve fiber density (SENFD) of PGP9.5 was significantly decreased and the axonal swelling ratio, a predictor of neuropathy, and upper dermis nerve fiber density (UDNFD) of PGP9.5, presumably representing sprouting of parasympathetic fibers, were significantly increased in BiPN patients. Finally, significant correlations between UDNFD of PGP9.5 versus the evaluative Pain Rating Index (PRI) and number of words count (NWC) of the MPQ, and significant inverse correlations between SENFD/UDNFD of CGRP versus the sensory-discriminative MPQ PRI/NWC were found. BiPN is a sensory neuropathy, in which neuropathic pain is the most striking clinical finding. Bortezomib-induced neuropathic pain may be driven by sprouting of parasympathetic fibers in the upper dermis and impaired regeneration of CGRP fibers in the subepidermal layer.

Increased aortic stiffness and blood pressure in non-classic Pompe disease.

Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99). Except for a shorter aortic reflexion time (p = 0.02), indirect indicators of arterial stiffness did not differ between patients and volunteers. Relative to volunteers (20%), more Pompe patients had a history of hypertension (36%, p = 0.005), and the MAP was higher than in volunteers (100 versus 92 mmHg, p < 0.001). This study shows that patients with non-classic Pompe disease have increased aortic stiffness and blood pressure. Whether this is due to glycogen accumulation requires further investigation. To reduce the potential risk of cardiovascular diseases, we recommend that blood pressure and other common cardiovascular risk factors are monitored regularly.

Assessment of transverse ultrasonographic parameters to optimize carpal tunnel syndrome diagnosis in a case-control study.

INTRODUCTION: Transverse ultrasound measurements of the median nerve (MN) for diagnosis of carpal tunnel syndrome (CTS) suffer from inconsistent findings within and between patients and healthy subjects. The objective of this study was to improve ultrasound assessment of CTS. METHODS: In a case-control study (51 patients, 25 controls) we evaluated the performance gained by: (1) correcting for ultrasound probe angulation; (2) including active parameters such as forceful gripping of the hand; and (3) including hand flexor tendon parameters. RESULTS: Correcting ultrasound probe angulation increased the correct classification rate by 4.5%; including forceful gripping resulted in increasing it by 2.8%; and including the hand flexor tendon resulted in an increase of 1.3%. CONCLUSIONS: The best predictive model combines correcting probe angulation with forceful gripping parameters and hand flexor tendon parameters. However, the clinically most practical model might use only probe angulation correction.

Ultrasonographic assessment of longitudinal median nerve and hand flexor tendon dynamics in carpal tunnel syndrome.

INTRODUCTION: Changes in subsynovial connective tissue (SSCT) in carpal tunnel syndrome (CTS) patients may result in altered dynamics; consequently, quantification of these dynamics might support objective diagnosis of CTS. METHODS: We measured and compared longitudinal excursion of the flexor digitorum superficialis and profundus tendons, the median nerve, and the SSCT between the most and least affected hands of 51 CTS patients during extension-to-fist motion. RESULTS: Median nerve and flexor digitorum superficialis tendon excursions in the most affected hands were smaller than in the least affected hands of the same patients, whereas the excursions of the flexor digitorum profundus were larger. Based on these excursions, logistic regression models classified between 67% and 86% of the hands correctly as having CTS. CONCLUSIONS: The altered hand dynamics in CTS patients may have implications for the pathophysiology and clinical evaluation of CTS, and ultrasound-based classification models may further support the diagnosis of CTS.

Guidelines for EEG in encephalopathy related to ESES/CSWS in children.

Electrical status epilepticus during slow sleep (ESES) or continuous spikes and waves during slow sleep (CSWS) is a phenomenon characterized by strong activation of epileptiform activity in the electroencephalogram (EEG) during sleep. The literature contains several small series of patients and many case reports. Large prospective studies are lacking. Definitions of the syndromes and EEG criteria and methods vary, as does their classification. The fluctuating clinical course and EEG findings complicate the diagnostic process and evaluation of effect of therapy. Studies describing quantitative aspects of the epileptiform abnormalities in EEG are overrepresented in literature, whereas qualitative aspects are relatively undervalued. Guidelines for evaluation of the EEG in these syndromes, which focus on both aspects, are presented.

Landau-Kleffner syndrome and CSWS syndrome: treatment with intravenous immunoglobulins.

This study reports results of therapy with immunoglobulin in children with Landau-Kleffner syndrome (LKS) or the syndrome of continuous spikes and waves during sleep (CSWS syndrome). In a prospective study, children diagnosed between 2002 and 2006 with either LKS or CSWS syndrome were treated soon after diagnosis with intravenous courses of immunoglobulin (IVIg). We compared the results with those reported in the literature and with data from a retrospective survey of our earlier patients. Six children (two girls), aged 4-9 years, were included. Three had LKS, and three had CSWS syndrome. One child-with typical LKS-had been treated with prednisone before (without response). No patient had seizures during IVIg treatment and follow-up. Their electroencephalography (EEG) findings did not improve. Neuropsychological improvement occurred in one child with CSWS syndrome. Three children did not show any beneficial effect; they were subsequently treated with steroids, one with a clearly positive result. We conclude that successful treatment of LKS and CSWS syndrome with IVIg occurs occasionally. However, the improvement cannot always be clearly attributed to this. It might also reflect the natural course of the disease. Although the temporal relation between IVIg treatment and clinical improvement cannot be denied in individual patients, its real value remains to be determined.

Biochemical, genetic, and zoosporicidal properties of cyclic lipopeptide surfactants produced by Pseudomonas fluorescens.

Zoospores play an important role in the infection of plant and animal hosts by oomycetes and other zoosporic fungi. In this study, six fluorescent Pseudomonas isolates with zoosporicidal activities were obtained from the wheat rhizosphere. Zoospores of multiple oomycetes, including Pythium species, Albugo candida, and Phytophthora infestans, were rendered immotile within 30 s of exposure to cell suspensions or cell culture supernatants of the six isolates, and subsequent lysis occurred within 60 s. The representative strain SS101, identified as Pseudomonas fluorescens biovar II, reduced the surface tension of water from 73 to 30 mN m-1. The application of cell suspensions of strain SS101 to soil or hyacinth bulbs provided significant protection against root rot caused by Pythium intermedium. Five Tn5 mutants of strain SS101lacked the abilities to reduce the surface tension of water and to cause lysis of zoospores. Genetic characterization of two surfactant-deficient mutants showed that the transposons had integrated into condensation domains of peptide synthetases. A partially purified extract from strain SS101 reduced the surface tension of water to 30 mN m-1 and reached the critical micelle concentration at 25 micrograms ml-1. Reverse-phase high-performance liquid chromatography yielded eight different fractions, five of which had surface activity and caused lysis of zoospores. Mass spectrometry and nuclear magnetic resonance analyses allowed the identification of the main constituent as a cyclic lipopeptide (1,139 Da) containing nine amino acids and a 10-carbon hydroxy fatty acid. The other four zoosporicidal fractions were closely related to the main constituent, with molecular massesranging from 1,111 to 1,169 Da.

Control of Fusarium Wilt of Radish by Combining Pseudomonas putida Strains that have Different Disease-Suppressive Mechanisms.

ABSTRACT Biological control of soilborne plant pathogens in the field has given variable results. By combining specific strains of microorganisms, multiple traits antagonizing the pathogen can be combined and this may result in a higher level of protection. Pseudomonas putida WCS358 suppresses Fusarium wilt of radish by effectively competing for iron through the production of its pseudobactin siderophore. However, in some bioassays pseudobactin-negative mutants of WCS358 also suppressed disease to the same extent as WCS358, suggesting that an, as yet unknown, additional mechanism may be operative in this strain. P. putida strain RE8 induced systemic resistance against fusarium wilt. When WCS358 and RE8 were mixed through soil together, disease suppression was significantly enhanced to approximately 50% as compared to the 30% reduction for the single strain treatments. Moreover, when one strain failed to suppress disease in the single application, the combination still resulted in disease control. The enhanced disease suppression by the combination of P. putida strains WCS358 and RE8 is most likely the result of the combination of their different disease-suppressive mechanisms. These results demonstrate that combining biocontrol strains can lead to more effective, or at least, more reliable biocontrol of fusarium wilt of radish.