Electronic search strategies fail to identify randomized controlled trials (RCTs) in neurosurgery Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): Rodrigo Panico Gorayeb, Maria João Forjaz, António Gonçalves Ferreira, Gonçalo N.S. Duarte, Tiago Machado, Joaquim José Ferreira Abstract Randomized controlled trials (RCTs) are the gold standard studies to evaluate the efficacy of therapeutic interventions. Although they are frequently identified through open searches in electronic databases, no studies have evaluated how easy it is to identify RCTs in neurosurgery using electronic search strategies. The present study evaluated the sensitivity and specificity of different search strategies applied to commonly used databases to identify RCTs in neurosurgery. The total number of RCTs in neurosurgery published between 1960 and 2013 was determined through a detailed search involving open keyword searches in PubMed, Cochrane Library and Center for Reviews and Dissemination (CRD) databases, a PubMed search based on clinical entity-related keywords and hand-searches on the reference list of identified articles. The sensitivity and specificity were calculated for the open keyword searches on PubMed, the Cochrane Library and the CRD database and for the Cochrane’s HSSS, based on the total number of the identified RCTs. Compared to the total of 1102 RCTs identified, PubMed open search yielded 4660 articles, among which 365 were RCTs (sensitivity: 33.1%; specificity: 7.8%). Cochrane open search yielded 621 among which 36 were RCTs (sensitivity: 3.2%; specificity: 5.8%) and CRD open search returned 78 articles, among which 4 were RCTs (sensitivity: 0.4% sensitivity; specificity: 5.1%). The Cochrane HSSS retrieved 10702 results, among which 340 were RCTs (sensitivity: 30.9%; specificity: 3.2%). Most RCTs in neurosurgery cannot be identified by commonly used search strategies, which emphasizes the need to improve their indexing.

“Limbic encephalitis with acute onset and Hu antibodies treated with rituximab: Paraneoplastic or non-paraneoplastic disorder?” Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): C. Lapucci, L. Benedetti, C. Tavarelli, C. Serrati, M. Godani, A. Schenone, D. Franciotta Abstract Paraneoplastic limbic encephalitis (PLE) associated with Hu antibodies is a rare autoimmune disorder usually characterized by subacute onset of slowly progressive neurocognitive symptoms. Small cell lung carcinoma is the most frequent PLE-associated cancer, which negatively affects the prognosis of the disease. We report on a patient with acute onset of confusional state and disorganized speech. Cerebrospinal fluid analysis and brain MRI temporal lesions corroborated the diagnostic suspects toward infectious or autoimmune encephalitis but testing for onconeural antibodies suggested the alternative diagnosis of PLE, in the absence of cancer (total-body CT and PET were negative). The patient's serum was positive for Hu antibodies, thus leading to a diagnosis of PLE. First-line immunotherapies were ineffective on the neurocognitive symptoms, which improved after rituximab. Six months later, a retropharyngeal peri-jugular mass was histopathologically diagnosed as a metastasis of lung neuroendocrine tumor. Still clinically improved, the patient died from the oncological disease-related complications. Testing for onconeural antibodies should be considered in patients with clinico-radiological features of acute infectious or autoimmune encephalitis.

The first case report of McLeod syndrome in an infant with a novel mutation (c.89C>A, p. Ser30X) in XK Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): Pei-Chao Tian, Yue Wang, Zheng Chen, Dan-Dan Shi, Huai-li Wang, Qiang Luo Abstract McLeod syndrome (MLS) is a rare multisystem disorder and X-linked recessive inheritance disorder caused by mutations of the X-linked Kx blood group (XK) gene. The manifestations progress slowly and mainly appear in middle age, which make it difficult to distinguish MLS from other neuromuscular disorders. Here, we present a case of a 10-month-old Chinese boy who was taken to hospital for herpes of the extremities and oral cavity along with febrile seizures in June 2017. The laboratory test revealed persistent elevated levels of serum creatine phosphokinase and abnormal liver function. The results of the electrocardiogram showed sinus tachycardia, and magnetic resonance imaging of the brain showed enlarged bilateral ventricles and third ventricle. Genetic analysis by next-generation sequencing revealed a novel nonsense mutation c.89C > A (p. Ser30X) in exon 1 of XK. To the best of our knowledge, this is the first case report of infants with MLS confirmed by genetic analysis.

Megalencephalic leukoencephalopathy with subcortical cysts without macrocephaly: A case study of comorbid Turner’s syndrome Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): Klára Brožová, Hana Krásničanová, Robert Rusina Abstract We present a case of megalencephalic leukoencephalopathy with subcortical cysts without macrocephaly and who initially presented with severe psychiatric symptoms. The patient presented with presented with late-onset secondary generalized focal motor seizures, gait ataxia and mild spasticity with hyperreflexia. MRI showed diffuse white matter hyperintensities and bilateral anterotemporal cysts. Genetic analysis confirmed the causal MLC1 mutation and Turner's syndrome. Surprisingly, our patient had no macrocephaly, which is a typical finding in MCL1 mutations; we emphasize that comorbid unrelated Turner's syndrome could explain the absence of macrocephaly: although short stature is typical, microcephaly is not associated with Turner's syndrome. Our observation thus argues for detailed investigations in cases presenting with an atypical clinical picture.

A longitudinal investigation of the endplate cystic lesion effect on oblique lumbar interbody fusion Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): Guang-Xun Lin, Vit Kotheeranurak, Teng-Hui Zeng, Akaworn Mahatthanatrakul, Jin-Sung Kim Abstract Objective To determine longitudinal effects of changes in endplate cystic lesions on oblique lumbar interbody fusion (OLIF), the relationship between bone healing and endplate cystic lesion changes, and clinical significance of cyst formation. Patients and Methods A total of 107 segments in 67 patients who underwent OLIF between January 2013 and July 2016 were examined in this retrospective study. Using computed tomography, radiographic examinations of endplate cystic lesion, positive or negative cyst formation, cage subsidence, and fusion status were performed. Clinical outcomes were measured using visual analogue scale (VAS) pain scores, Oswestry disability index (ODI), and modified Macnab criteria. Outcomes were compared with preoperatively and postoperatively. A logistic regression analysis was performed to evaluate the relationship between measurements for endplate cysts. Results The fusion rate after OLIF was 94.4% at 2-year follow-up, with 86% of cases reporting satisfactory outcome (based on modified Macnab criteria). A significantly higher (P <  0.01) VAS score for back pain was observed in the cystic lesion group than non-cystic lesion group at 6-month follow-up. Cage subsidence significantly increased the risk of non-union (odds ratio [OR]: 17.24; 95% confidence interval [CI]: 1.67–178.09). Positive cyst sign was a significant risk factor for cage subsidence (OR: 8.52; 95% CI: 2.73–26.62) while cage subsidence was also a significant risk factor for positive cyst formation (OR: 8.37; 95% CI: 2.71–25.89). Conclusions Cystic lesion may increase back pain in the early postoperative period. However, the preoperative cystic lesion does not aggravate a positive cyst formation or affect the final clinical result. Positive cyst formation was a significant risk factor for cage subsidence. In addition, cage subsidence was a significant predictor of non-union. Thus, the authors can speculate that positive cyst sign was potentially an indirect predictor of non-union.

The prognostic value of spirometric tests in Amyotrophic Lateral Sclerosis patients Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): Alice Pirola, Elisa De Mattia, Andrea Lizio, Giulia Sannicolò, Elena Carraro, Fabrizio Rao, Valeria Sansone, Christian Lunetta Abstract Objective Amyotrophic lateral sclerosis (ALS) patients tend to develop progressive respiratory muscle weakness, leading to ventilatory failure and ineffective cough, principal causes of morbidity and mortality. Since patients are usually unaware of these symptoms, these are generally not noticed until the advanced stages and are associated with poor prognosis. The monitoring of respiratory function on a regular basis is therefore of great importance. Despite the availability of several pulmonary function tests, none of them was found to be the best indicator of the disease progression throughout the course of this condition. The main aim of our work was to evaluate the prognostic value of these respiratory measures evaluated in a brief period of observation and their correlation with motor functional impairments in an ALS cohort. Patients and Methods Patients with ALS who had respiratory assessments performed and functional motor scales administered at baseline and six months later were included. All patients were assessed with forced vital capacity, both in seated and supine position (FVC; sFVC), peak expiratory flow (PEF), peak expiratory cough flow (PCEF), the revised ALS functional rating scale (ALSFRS-R), at baseline and after six months, and their disease progression rate (ΔFS) was obtained. Results We included 73 patients with probable or definite ALS according to El-Escorial revised Criteria. At baseline, PCEF and PEF significantly correlated with ALSFRS-R total, bulbar and spinal subscores and ΔFS, while FVC% significantly correlated with ΔFS. After 6 months all the respiratory parameters significantly correlated with ALSFRS-R and all its subscores. Longitudinally, FVC%, sFVC% and PCEF significantly correlated with ΔFS and some of ALSFRS-R subscores. As concerns the survival analysis, monthly declines of FVC% and sFVC%, significantly correlated with the survival. The worse prognosis in terms of survival was finally found in those whose FVC% and sFVC% dropped below their respective cut-offs. Conclusion Throughout the course of ALS disease, the monitoring of several respiratory markers, namely FVC, sFVC, PEF and PCEF, plays a critical role in predicting the prognosis of these subjects, both in terms of survival and functional ability. The implementation of monthly cut-offs in the evaluation of FVC and sFVC may allow a faster recognition of those patients with worse prognosis and therefore an optimized tailored clinical care, as well as a better stratification in clinical trials.

Uric acid is a useful marker to differentiate between responsive and refractory status epilepticus Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): Jun Young Choi, Ji Man Hong, Tae Joon Kim, Byung Gon Kim, Kyoon Huh Abstract Objectives Early recognition of refractory status epilepticus (RSE) is essential to select an appropriate treatment strategy and is closely associated with the outcome. Only few studies of RSE biomarkers exist; hence, we investigated the serum levels of uric acid (UA), albumin, and C-reactive protein (CRP) as potential serologic biomarkers for RSE. Patients and Methods Consecutive status epilepticus (SE) patients who had serial conventional blood tests in a referral hospital over a period of 10 years were retrospectively analyzed. Patients with anoxic encephalopathy, renal failure, acute stroke, and myocardial infarction were excluded. RSE was defined as seizure continuing after the first- and second-line treatments. We also assessed SE severity in all included patients using the Status Epilepticus Severity Score (STESS). General demographics and blood test findings were compared between responsive SE and RSE patients. Results A total of 141 patients (99 responsive and 42 refractory) were recruited from our SE registry. Compared to responsive patients, patients with RSE showed a higher STESS, lower initial albumin levels, lower initial UA levels, lower follow-up UA levels, and greater reduction of UA levels. The RSE group more frequently had acute symptomatic etiology, showed longer hospitalization, and had poorer functional outcomes compared to the responsive-SE group. All evaluated UA level parameters exhibited significant areas under the curve in receiver operating characteristic analyses, predictive of RSE. Initial UA levels, as well as changes therein, were significantly associated with RSE in multivariate logistic regression analysis. Conclusion UA levels at initial and follow-up evaluations, and changes therein differentiated responsive SE and RSE, demonstrating the feasibility of UA serum levels as a biomarker for RSE.

The effect of diabetes mellitus on in-hospital hyperglycemia, length of stay and survival in patients with brain tumor receiving dexamethasone: A descriptive and comparative analysis Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): Panteleimon Pantelidis, Parmenion P. Tsitsopoulos, Eleni Pappa, Elpida Theologou, Nikolaos Karanikolas, Christos Drosos, Christos Tsonidis Abstract Objectives To perform a comparative analysis on the impact of Type 2 Diabetes Mellitus (DM) on in-hospital hyperglycemia, length of stay (LOS) and survival of patients suffering from brain tumor who receive dexamethasone. Patients and Methods Patients with brain tumor hospitalized in a Neurosurgery department between 2011 and 2018, were studied. Data referring to medical history, clinical characteristics and in-hospital survival was collected and analyzed. Morning plasma glucose levels (PGL) were obtained for seven consecutive days after the start of dexamethasone. Results Fifty-six patients were identified. Of them, 21 (37.5%) were diabetic. During dexamethasone administration, a difference in morning PGL values during different days was noted (p = 0.003). No difference in glucose levels among different glucocorticoid doses was seen. DM was associated with higher average PGL (aMPGL), calculated as the mean of morning PGL values for the last six days (p = 0.001) and with higher rates of persistent hyperglycemia (p = 0.002). The change of aMPGL from the morning PGL value of day one did not differ between the two cohorts (p = 0.729). DM neither affected LOS nor in-hospital survival (p = 0.745 & p = 0.438, respectively). Conclusion Although morning glucose values were higher in diabetic, compared to non-diabetic patients, their change from day one was similar between the two cohorts. LOS and in-hospital survival were not affected by DM. Graphical abstract

Real-world effectiveness of fingolimod in Polish group of patients with relapsing-remitting multiple sclerosis Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): Agata Walczak, Iwona Kurkowska-Jastrzebska, Beata Zakrzewska-Pniewska, Malgorzata Dorobek, Waldemar Brola, Radoslaw Zajdel, Halina Bartosik-Psujek, Mariusz Stasiolek, Alina Kulakowska, Stanislaw Rusek, Andrzej Tutaj, Andrzej Glabinski, Agata Wlodek, Jan Kochanowski, Agnieszka Ciach, Malgorzata Siger, Katarzyna Kurowska, Wojciech Wicha, Monika Nojszewska, Aleksandra Podlecka-Pietowska Abstract Objectives Fingolimod is indicated for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with highly aggressive disease characterized by frequent relapses and active magnetic resonance imaging. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. Fingolimod in licensed in Europe since 2011 but with a growing number of disease-modifying drugs (DMD) becoming available for RRMS, it is important to gather real-world evidence data regarding long-term effectiveness in treated patients with MS. The aim of this study was to assess fingolimod effectiveness in a real life Polish group of RRMS patients receiving fingolimod as second line treatment. Patients and methods The observational study with retrospective data collection was performed at 13 sites that were asked to document eligible patients in consecutive chronological order to avoid selection bias. Demographic and clinical data from 253 adult patients with RRMS treated with fingolimod were analyzed. Results Mean treatment time with fingolimod was 42 months. Relapses reduction during 3 years treatment period was observed (2.0 v 0.2) and majority of patients were free of relapses. Mean EDSS score was stable during the time of observation. The proportion of patients who were free from any clinical disease activity, i.e. without relapses and disability progression, was over 70%. During the first and second year of observation significant reduction of new MRI lesions was observed. Conclusion In the Polish group of patients with RRMS treated with fingolimod, the majority of them showed freedom from relapses, disability progression and reduction of new MRI lesions. Switching from injectable immunomodulatory drugs to fingolimod is associated with fewer relapses and lower disability progression.

Factors other than body weight predicting heparin loading to acquire optimal activated clotting time in endovascular neurointerventions Publication date: September 2019 Source: Clinical Neurology and Neurosurgery, Volume 184 Author(s): Jumpei Oshita, Shigeyuki Sakamoto, Toshinori Matsushige, Takahito Okazaki, Daizo Ishii, Reo Kawano, Kaoru Kurisu Abstract Objectives The aim of this study was to investigate the relationship between the activated clotting time (ACT) and heparin loading based on body weight (BW), and factors other than BW that may contribute to the ACT after heparin loading to establish a more accurate regimen for achieving ACT targets during endovascular neurointerventions. Patients and Methods : Japanese patients who underwent endovascular coiling of unruptured intracranial aneurysms or carotid artery stenting in our institution between January 2014 and November 2017 were enrolled. The ACT was measured before (pre–ACT) and 3 min after heparinization (post–ACT). The correlation between ACT and heparin loading based on BW and factors that may contribute to the ACT after heparin loading were analyzed retrospectively. Results : A total of 199 cases (109 males, age: 66 ± 12 years) were analyzed. There were positive correlations between the heparin loading per kg of BW and post–ACT, post–ACT – pre–ACT (ΔACT) (Spearman’s r = 0.2946, 0.2633, P: <0.0001, 0.0002, respectively). Heparin loading per kg of BW, gender, hematocrit (Ht), estimate glomerular filtration rate (eGFR) were significant confounding factors to ΔACT. The calculated predicted ΔACT based on these significant factors was found to be highly correlated with ΔACT compared with the heparin loading per kg of BW. (Spearman’s r = 0.5820, P = <0.0001). Conclusion Initial BW–based heparin loading is a simple way in endovascular neurointerventions. ACT after heparin loading based on BW has individual differences greatly, it is possible to estimate more accurately the heparin loading for acquiring the optimal ACT considering not only BW but also gender, Ht and eGFR.