The semiology of psychogenic nonepileptic seizures revisited: Can video alone predict the diagnosis? Preliminary data from a prospective feasibility study.

OBJECTIVE: To investigate if, when, and to what extent visual information contained in a video-recorded event allows experienced epileptologists to predict the diagnosis of psychogenic nonepileptic seizures (PNES) without the aid of electroencephalography (EEG). METHODS: Five neurologists actively practicing in epilepsy centers in Italy and the United States were asked to review 23 videos capturing representative events of 21 unselected consecutive patients admitted for long-term video-EEG monitoring (VEM). Four raters were blind to EEG and clinical information; one rater was not. They were requested to (1) rate the videos for quality and content; (2) choose among four diagnoses: (a) epileptic seizures (ES); (b) PNES; (c) Other nonepileptic seizures (NES; (syncope, movement disorder, migraine, etc.); (d) "Cannot Say"; and (3) explain in their own words the main reasons leading to the diagnosis of choice. RESULTS: All raters predicted the diagnosis correctly in 7 of 23 videos (all ES or PNES) (30.4%), whereas all raters failed in 5 of 23 cases (three Other NES, one PNES, one Cannot Say) (21.7%). The conditions that facilitate, and those that interfere with, a confident diagnosis were predictable. Degree of accuracy among raters was not uniform and was consistently better in three raters. Two among the four blind raters were as accurate as the rater who was not blinded. Interrater agreement was "moderate" (k = 0.52) for the overall group; "moderate" for ES (k = 0.53); "substantial" for PNES (k = 0.63); "fair" for Other NES (k = 0.21)-similar to the results obtained in a previous study evaluating the reliability of combined video-EEG. SIGNIFICANCE: In about one third of cases, a confident diagnosis of PNES/ES can be established on clinical grounds based on video data alone. Our results benefit all affected patients, particularly those with no access to video-EEG monitoring units.

Validation of a novel classification model of psychogenic nonepileptic seizures by video-EEG analysis and a machine learning approach.

The aim of this study was to validate a novel classification for the diagnosis of PNESs. Fifty-five PNES video-EEG recordings were retrospectively analyzed by four epileptologists and one psychiatrist in a blind manner and classified into four distinct groups: Hypermotor (H), Akinetic (A), Focal Motor (FM), and with Subjective Symptoms (SS). Eleven signs and symptoms, which are frequently found in PNESs, were chosen for statistical validation of our classification. An artificial neural network (ANN) analyzed PNES video recordings based on the signs and symptoms mentioned above. By comparing results produced by the ANN with classifications given by examiners, we were able to understand whether such classification was objective and generalizable. Through accordance metrics based on signs and symptoms (range: 0-100%), we found that most of the seizures belonging to class A showed a high degree of accordance (mean±SD=73%±5%); a similar pattern was found for class SS (80% slightly lower accordance was reported for class H (58%±18%)), with a minimum of 30% in some cases. Low agreement arose from the FM group. Seizures were univocally assigned to a given class in 83.6% of seizures. The ANN classified PNESs in the same way as visual examination in 86.7%. Agreement between ANN classification and visual classification reached 83.3% (SD=17.8%) accordance for class H, 100% (SD=22%) for class A, 83.3% (SD=21.2%) for class SS, and 50% (SD=19.52%) for class FM. This is the first study in which the validity of a new PNES classification was established and reached in two different ways. Video-EEG evaluation needs to be performed by an experienced clinician, but later on, it may be fed into ANN analysis, whose feedback will provide guidance for differential diagnosis. Our analysis, supported by the ML approach, showed that this model of classification could be objectively performed by video-EEG examination.

Management of Patients Affected by Giant Cell Arteritis during the COVID-19 Pandemic: Telemedicine Protocol TELEMACOV.

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries, prevalently affecting elderly people. Both early diagnosis and regular monitoring are necessary for the correct management of GCA. Following the outbreak of the COVID-19 pandemic, government decisions aiming at reducing the contagion led to reductions in health activities, limiting them to urgent cases. At the same time, remote monitoring activities have been implemented through telephone contacts or video calls carried out by specialists. In line with these deep changes affecting the worldwide healthcare system and in consideration of the high risk of GCA morbidity, we activated the TELEMACOV protocol (TELEmedicine and Management of the patient affected by GCA during the COVID-19 pandemic) in order to remotely monitor patients affected by GCA. The aim of this study was to evaluate the effectiveness of telemedicine in the follow-up of patients already diagnosed with GCA. This was a monocenter observational study. Patients with a previous diagnosis of GCA admitted to the Rheumatology Unit of the University Hospital "Città della Salute e della Scienza" in Turin were monitored every 6-7 weeks by means of video/phone calls from 9 March to 9 June 2020. All patients were asked questions concerning the onset of new symptoms or their recurrence, exams carried out, changes in current therapy, and satisfaction with video/phone calls. We performed 74 remote monitoring visits in 37 GCA patients. Patients were mostly women (77.8%) and had a mean age of 71.85 ± 9.25 years old. The mean disease duration was 5.3 ± 2.3 months. A total of 19 patients received oral glucocorticoids (GC) alone at the time of diagnosis with a daily dose of 0.8-1 mg/kg (52.7 ± 18.3 mg) of prednisone, while 18 patients were treated with a combination of oral steroids (at the time of diagnosis, the prednisone mean dose was 51.7 ± 18.8 mg) and subcutaneous injections of tocilizumab (TCZ). During the follow-up, patients additionally treated with TCZ reduced their GC dose more than patients treated with GC alone (p = 0.03). Only one patient, who was treated with GC alone, had a cranial flare and needed to increase the dosage of GC, which led to rapid improvement. Furthermore, all patients proved very adherent to the therapies (assessed by Medication Adherence Rating Scale (MARS)) and considered this type of monitoring very satisfactory according to a Likert scale (mean score 4.4 ± 0.2 on a 1-5 range). Our study shows that telemedicine can be safely and effectively used in patients with GCA under control as a possible alternative, at least for a limited period of time, to traditional visits.

Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study.

We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, previously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontinuation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 ± 13.8 years and with an ETA duration of 4.1 ± 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients.

Autoantibodies and Rheumatologic Manifestations in Hepatitis C Virus Infection.

HCV is a virus that can cause chronic infection which can result in a systemic disease that may include many rheumatologic manifestations such as arthritis, myalgia, sicca syndrome, cryoglobulinemia vasculitis as well as other non-rheumatological disorders (renal failure, onco-haematological malignancies). In this population, the high frequency of rheumatoid factor (45-70%), antinuclear (10-40%) and anticardiolipin (15-20%) antibodies is a B-cell mediated finding sustained by the infection. However, the possibility that a primitive rheumatic pathology may coexist with the HCV infection is not to be excluded thus complicating a differential diagnosis between primitive and HCV-related disorders.

Efficacy and safety of a single switch from etanercept originator to etanercept biosimilar in a cohort of inflammatory arthritis.

AntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars; therefore, such a transition is increasingly encouraged both in the US and Europe. However, there are reports about flares and adverse events (AE) as a non-medical switch remains controversial due to ethical and clinical implications (efficacy, safety, tolerability). The aim of our work was to evaluate the disease activity trend after switching from etanercept originator (oETA-Enbrel) to its biosimilar (bETA-SP4/Benepali) in a cohort of patients in Turin, Piedmont, Italy. In this area, the switch to biosimilars is stalwartly encouraged. We switched 87 patients who were in a clinical state of stability from oETA to bETA: 48 patients were affected by Rheumatoid Arthritis (RA),26 by Psoriatic Arthritis (PsA) and 13 by Ankylosing Spondylitis (AS).We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, Disease Activity Score on 28 joints (DAS28) for RA, Disease Activity in Psoriatic Arthritis (DAPSA) for PsA, Health Assessment Questionnaire (HAQ) and Health Assessment Questionnaire for the spondyloarthropathies (HAQ-S),Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. 11/85 patients (12.6%) stopped treatment after switching to biosimilar etanercept. No difference was found between oETA and bETA in terms of efficacy. However, some arthritis flare and AE were reported. Our data regarding maintenance of efficacy and percentage of discontinuation were in line with the existing literature.

Rheumatologic manifestations of hepatitis C in the era of direct-acting antiviral agents.

Beyond the classic hepatic complications, hepatitis C (HCV) infection is considered as a systemic disease, since extrahepatic manifestations become clinically evident in 40% to 70% of the patients and it can frequently include rheumatic ones. Furthermore, HCV can promote the production of several autoantibodies, thus complicating the differential diagnosis between primitive and HCV-related rheumatic disorders. The recent development of direct-acting antivirals (DAA) against HCV has revolutionized the field, reducing the damage stemming from systemic inflammatory phenomena and persistent immune activation associated with continuous HCV replication. Our review focuses on the main rheumatologic manifestations associated with chronic HCV infection as well as the impact of DAA interferon-free treatments on such extrahepatic clinical involvement.

Ultrasound-guided intra-articular injection: efficacy of hyaluronic acid compared to glucocorticoid in the treatment of knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease which causes pain and functional impairment in adults over 50 years old with consequent important disability. Unfortunately, there is no definitive cure for OA, thus the approach is characterized by multiple treatments that can manage its symptoms. Even though data from randomized controlled trials and meta-analyses indicate that intra-articular hyaluronic acid (IAHA) offers the best benefit/risk balance among the various pharmacologic treatments to improve OA-related knee pain, there is a lack of agreement among national and international guidelines about such uses of IAHA for the medical management of symptomatic knee OA. To minimize confounding factors and biases, the aim of our study was to evaluate the efficacy of the different weight and concentration of IAHA treatment in patients suffering from knee OA comparing to glucocorticoids (GC) joint injections. Furthermore, to make the procedure more accurate and assessment more objective, we use ultrasonography (US) with power Doppler (PWD) to help us differentiate between active and inactive inflammation within joints and periarticular soft tissues. METHODS: We performed a retrospective evaluation of a cohort of patients with knee OA, diagnosed according to the ACR criteria, treated by US-guided joint injection of HA and GC. The patients were catalogued according to the type of treatment they underwent: group A, patients treated with HA (1.5%) >1500 kDa (three US-guided knee injections one week apart); group B, patients treated with HA (2%) 800-1200 kDa (three US-guided knee injections one week apart); group C, patients treated with glucocorticoids (three US-guided knee injections of triamcinolone acetate 40 mg one week apart). All patients were monitored for 6 months, evaluating: subjective pain using a 10-cm Visual Analogue Scale; pain, stiffness, and functionality using the Western Ontario and McMaster Universities Arthritis Index (WOMAC); the concomitant intake of anti-inflammatory and/or analgesic drugs through a questionnaire; and US results by grey scale and PWD. RESULTS: A total of 171 patients affected by knee OA were evaluated (women 72.3%) with a mean age of 69.3±4.1 years. All the subjects analyzed showed a pain reduction at 6 months after treatment (group A: -39.5; group B: -36.9; group C: -30.8). The difference between the three groups was statistically significant (Kruskall-Wallis P=0.001) and in particular between group A and group C (P=0.000) and between group B and group C (P=0.005), but not between A and B (P=0.258). WOMAC was statistically significantly improved from baseline in all groups examined (group A: -11.9; group B: -14.9; group C: -11.2). The PWD score showed a statistically significant improvement in group B (-0.64) even after 6 months (P=0.004). All patients in the different groups showed a statistically significant reduction of concomitant therapy compared to baseline with respect to paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs)/COX2 therapy, while only group B showed a statistically significant reduction for opioids. CONCLUSIONS: This study demonstrated the efficacy of OA treatment with medium molecular weight HA in favor of the higher concentration of HA that may affect the reduction of pro-inflammatory mediators. Furthermore, US monitoring allowed to evaluate aspects related to synovial involvement, which cannot be appreciated with standard imaging.

The clinical presentation in adulthood of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic systemic inflammatory disease, which affects children and adolescents, characterized by significant differences when compared to inflammatory rheumatisms in adulthood. Today, in a panorama enriched in the last decades with great improvements in the diagnostic and therapeutic field, a far from negligible portion and an increasing number of patients with JIA require the continuation of treatments in adulthood. This specific population of patients, given the high incidence of extra-articular manifestations, residual irreversible disabilities, comorbidities related to an inflammatory process and extended immunosuppressive treatments during the age of development, requires precise attentions in the follow-up and a multidisciplinary approach characterized by different clinical, psychological and social aspects.

Serological and clinical profile of systemic sclerosis: analysis in a cohort of patients from a single center in Northern Italy.

BACKGROUND: The purpose of this study was to identify the frequency of autoantibodies among patients affected by systemic sclerosis (SSc) in our Rheumatology Center and analyze the correlation between serological and clinical presentations. METHODS: An automated fluoro-enzyme-immunoassay is used for the qualitative detection of sixteen antibodies: anti-dsDNA, antiRo52, antiRo60, antiSS-B, antiTopoisomerasi-I, antiCENP-B, anti-fibrillarin, antiMi-2, anti-Sm, antiU1sn-RNP, antiRNP70, antiPm/Scl100, antiPCNA, antiJo-1, antiRibosomal-P, antiRNA-Polymerase-III. These parameters were further correlated with clinical presentation of the disease. RESULTS: One-hundred and six patients who fulfilled the ACR classification criteria of SSc have been screened. Similarly to the findings of other studies, a strong association between anti-Centromere antibodies and clinical indicators of better prognosis has been showed; conversely, the anti-Scl70 antibodies are associated with diffuse SSc and higher severity. Some antibodies (antiR052, antiU1RNP) are correlated with a diagnosis of autoimmune overlap. A protective effect of AntiCentromere regarding pulmonary fibrosis and skin ulcers has been shown (P<0.05). The presence of AntiScl70 correlated with cardiac involvement (arrhythmias, pericarditis and myocarditis) and the Anti-U1RNP correlated with the presence of skin ulcers. CONCLUSIONS: The diagnostic importance of SSc antibodies against a variety of nuclear and cytoplasmic antigens has become increasingly recognized, as confirmed by the inclusion into 2013American College of Rheumatology (ACR)/the European League Against Rheumatism clinical classification criteria for SSc. A number of studies reported variable geographic rates of antibody prevalence in SSc, which may be related to either genetic or environmental factors. However, the association of specific antibodies with clinical manifestations continues to be claimed. New testing methods which include a wider spectrum of detectable antibodies may support the daily rheumatological and dermatological clinical practice in defining clinical subsets of disease and provide prognostic information.

3T Double Inversion Recovery Magnetic Resonance Imaging: diagnostic advantages in the evaluation of cortical development anomalies.

PURPOSE: The aim of this work was to investigate the diagnostic value of the DIR sequence at 3T MR imaging operating in the evaluation of cortical development anomalies. METHODS: We studied 40 patients, with a previous diagnosis of cortical dysplasia, by FLAIR-3D, DIR, FSE T2 and MPR-GE T1 sequences at 3T MRI. Two independent observers evaluated, for each sequence and lesion, some semiological aspects (cortical thickness, cortical signal intensity, white-gray matter blurring, subcortical white matter intensity). We made also a quantitative evaluation of the cortical signal intensity in lesion site, drawing a ROI on each MRI sequences and comparing them to the correspondent normal contralateral cortical area. RESULTS: We identified 44 cortical development anomalies. Qualitative analyses showed a high level of agreement between the observers concerning DIR potentialities in detecting and characterizing the cortical development disorders. Particularly DIR sequence was able to demonstrate the blurring and the subcortical white matter anomalies. The quantitative analyses didn't show a significant difference between DIR and traditional sequences in the evaluation of the cortical signal intensity. CONCLUSION: 3T MRI-DIR sequence is a useful and better suitable sequence compared to the traditional sequences in the characterization of some semiological aspects of the cortical development disorders, particularly blurring and subcortical white matter hyperintensity.

Slow repetitive TMS for drug-resistant epilepsy: clinical and EEG findings of a placebo-controlled trial.

PURPOSE: To assess the effectiveness of slow repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for drug-resistant epilepsy. METHODS: Forty-three patients with drug-resistant epilepsy from eight Italian Centers underwent a randomized, double-blind, sham-controlled, crossover study on the clinical and EEG effects of slow rTMS. The stimulus frequency was 0.3 Hz. One thousand stimuli per day were given at the resting motor threshold intensity for 5 consecutive days, with a round coil at the vertex. RESULTS: "Active" rTMS was no better than placebo for seizure reduction. However, it decreased interictal EEG epileptiform abnormalities significantly (p < 0.05) in one-third of the patients, which supports a detectable biologic effect. No correlation linked the rTMS effects on seizure frequency to syndrome or anatomic classification, seizure type, EEG changes, or resting motor threshold (an index of motor cortex excitability). CONCLUSIONS: Although the antiepileptic action was not significant (p > 0.05), the individual EEG reactivity to "active" rTMS may be encouraging for the development of more-powerful, noninvasive neuromodulatory strategies.

Prevalence and characteristics of epilepsy in the Aeolian islands.

PURPOSE: To estimate the prevalence and define the clinical characteristics of epileptic disorders in the 13,431 residents of the Sicilian Aeolian archipelago, on June 1, 1999. METHODS: All established or suspected cases were identified by the neurologists of our working group from available medical information sources. Possible epilepsy cases were then evaluated by the epileptologists by using a standardized questionnaire. The patients were further reviewed by the whole research team to confirm the clinical diagnosis. For a more detailed syndromic definition, some patients underwent EEG or neuroradiologic investigations or both. RESULTS: The crude point prevalence rate of active epilepsy was 3.13 (95% confidence interval, 2.2-4.2). The prevalence rate age-adjusted to the 2001 Italian population was 3.01. Females had a slightly higher prevalence rate than did males. The highest age-specific prevalence was found in patients aged 5 to 14 years (5.05) and in those aged 65 to 74 years (5.41). Partial seizures with or without secondary generalization were more common (61.7%) than were generalized seizures. Eighty-three percent of cases had symptomatic or cryptogenic localization-related epilepsies, and 8.5% had idiopathic (generalized or partial) epilepsies. Epilepsy was unclassified in 8.5% of cases. CONCLUSIONS: The prevalence of active epilepsy in the Aeolian islands is lower than that in other developed areas, including northern Italy, but is similar to that in Sicily. Partial seizures were the most common type, and localization-related symptomatic epilepsies were the largest syndromic category.