Source localization using virtual magnetoencephalography helmets: A simulation study toward a prior-based tailored scheme.

Magnetoencephalography (MEG) source estimation of brain electromagnetic fields is an ill-posed problem. A virtual MEG helmet (VMH), can be constructed by recording in different head positions and then transforming the multiple head-MEG coordinates into one head frame (i.e., as though the MEG helmet was moving while the head remained static). The constructed VMH has sensors placed in various distances and angles, thus improving the spatial sampling of neuromagnetic fields. VMH has been previously shown to increase total information in comparison to a standard MEG helmet. The aim of this study was to examine whether VMH can improve source estimation accuracy. To this end, controlled simulations were carried out, in which the source characteristics are predefined. A series of VMHs were constructed by applying two or three translations and rotations to a standard 248 channel MEG array. In each simulation, the magnetic field generated by 1 to 5 dipoles was forward projected, alongside noise components. The results of this study showed that at low noise levels (e.g., averaged data of similar signals), VMHs can significantly improve the accuracy of source estimations, compared to the standard MEG array. Moreover, when utilizing a priori information, tailoring the constructed VMHs to specific sets of postulated neuronal sources can further improve the accuracy. This is shown to be a robust and stable method, even for proximate locations. Overall, VMH may add significant precision to MEG source estimation, for research and clinical benefits, such as in challenging epilepsy cases, aiding in surgical design.

Digital Semiology: A Prototype for Standardized, Computer-Based Semiologic Encoding of Seizures.

Video-EEG monitoring (VEM) is imperative in seizure classification and presurgical assessment of epilepsy patients. Analysis of VEM is currently performed in most institutions using a freeform report, a time-consuming process resulting in a non-standardized report, limiting the use of this essential diagnostic tool. Herein we present a pilot feasibility study of our experience with "Digital Semiology" (DS), a novel seizure encoding software. It allows semiautomated annotation of the videos of suspected events from a predetermined, hierarchal set of options, with highly detailed semiologic descriptions, somatic localization, and timing. In addition, the software's semiologic extrapolation functions identify characteristics of focal seizures and PNES, sequences compatible with a Jacksonian march, and risk factors for SUDEP. Sixty episodes from a mixed adult and pediatric cohort from one level 4 epilepsy center VEM archives were analyzed using DS and the reports were compared with the standard freeform ones, written by the same epileptologists. The behavioral characteristics appearing in the DS and freeform reports overlapped by 78-80%. Encoding of one episode using DS required an average of 18 min 13 s (standard deviation: 14 min and 16 s). The focality function identified 19 out of 43 focal episodes, with a sensitivity of 45.45% (CI 30.39-61.15%) and specificity of 87.50% (CI 61.65-98.45%). The PNES function identified 6 of 12 PNES episodes, with a sensitivity of 50% (95% CI 21.09-78.91%) and specificity of 97.2 (95% CI 88.93-99.95%). Eleven events of GTCS triggered the SUDEP risk alert. Overall, these results show that video recordings of suspected seizures can be encoded using the DS software in a precise manner, offering the added benefit of semiologic alerts. The present study represents an important step toward the formation of an annotated video archive, to be used for machine learning purposes. This will further the goal of automated VEM analysis, ultimately contributing to wider utilization of VEM and therefore to the reduction of the treatment gap in epilepsy.

Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis.

In this study (trial registration: NCT02166021), we aimed to evaluate the optimal way of administration, the safety and the clinical efficacy of mesenchymal stem cell (MSC) transplantation in patients with active and progressive multiple sclerosis. Forty-eight patients (28 males and 20 females) with progressive multiple sclerosis (Expanded Disability Status Scale: 3.0-6.5, mean : 5.6 ± 0.8, mean age: 47.5 ± 12.3) and evidence of either clinical worsening or activity during the previous year, were enrolled (between 2015 and 2018). Patients were randomized into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1 × 106/kg) or sham injections. After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into two subgroups and treated with either MSC-IT or MSC-IV. The study duration was 14 months. No serious treatment-related safety issues were detected. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = 0.0003 and P = 0.0008). During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, exhibited no evidence of disease activity compared with 9.7% in the sham-treated group (P < 0.0001 and P < 0.0048, respectively). MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Treatment with MSCs was well-tolerated in progressive multiple sclerosis and induced short-term beneficial effects regarding the primary end points, especially in the patients with active disease. The intrathecal administration was more efficacious than the intravenous in several parameters of the disease. A phase III trial is warranted to confirm these findings.

[AUTOIMMUNE ENCEPHALITIS: A BRIDGE BETWEEN NEUROLOGY AND PSYCHIATRY].

INTRODUCTION: Autoimmune encephalitis (AIE) usually manifests as an acute illness with psychosis, seizures and an amnestic disorder, although the clinical spectrum extends beyond this triad. The discovery of novel cell surface antibodies and antibodies directed at ion channels has revolutionized our understanding of the pathophysiology of the disease and the diagnostic tools at hand. Early diagnosis is crucial to initiation of treatment early in the disease course, which ameliorates the neurological outcome. OBJECTIVES: To delineate the clinical, imaging and laboratory characteristics of patients with AIE, as reflected in the cohort of limbic encephalitis patients treated in our department. METHODS: Patients diagnosed with AIE in our department in 2008-2018 were included in this retrospective study. All patients met the criteria for clinically probable or definite AIE, based on their clinical, laboratory and imaging findings, and the identification of causative autoantibodies. RESULTS: A total of 27 patients with a diagnosis of AIE were diagnosed and treated in our department in 2008-2018; 74% had an amnestic disorder and 70% developed seizures. Psychosis was observed in 37%, though 63% showed behavioral changes; 59% had clinically relevant autoantibodies in their cerebrospinal fluid (CSF). Approximately half had pathologic brain imaging (59%) and only 33% had CSF pleocytosis. Despite immunosuppressive treatment, residual neurologic deficits were seen in the majority of the patients. DISCUSSION: The diagnosis of AIE relies mainly on the clinical presentation, with normal ancillary studies in many cases. Thus, high clinical suspicion and prompt initiation of treatment despite lack of objective evidence of the diagnosis are necessary to limit the neurological sequela. Moreover, high awareness of AIE may allow appropriate workup and diagnosis in atypical cases.

Cortical functional modifications following optic neuritis.

BACKGROUND: We have recently suggested that delayed visual evoked potential (VEP) latencies in the fellow eye (FE) of optic neuritis patients reflect a cortical adaptive process, to compensate for the delayed arrival of visual information via the affected eye (AE). OBJECTIVE: To define the cortical mechanism that underlies this adaptive process. METHODS: Cortical activations to moving stimuli and connectivity patterns within the visual network were tested using functional magnetic resonance imaging (MRI) in 11 recovered optic neuritis patients and in 11 matched controls. RESULTS: Reduced cortical activation in early but not in higher visual areas was seen in both eyes, compared to controls. VEP latencies in the AEs inversely correlated with activation in motion-related visual cortices. Inter-eye differences in VEP latencies inversely correlated with cortical activation following FE stimulation, throughout the visual hierarchy. Functional correlation between visual regions was more pronounced in the FE compared with the AE. CONCLUSION: The different correlation patterns between VEP latencies and cortical activation in the AE and FE support different pathophysiology of VEP prolongation in each eye. Similar cortical activation patterns in both eyes and the fact that stronger links between early and higher visual areas were found following FE stimulation suggest a cortical modulatory process in the FE.