Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive–compulsive disorder (OCD) and Tourette's syndrome (TS)

There is evidence that motor and premotor cortex are hyperexcitable in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). We tested whether low-frequency repetitive transcranial magnetic stimulation (rTMS) could normalize overactive motor cortical regions and thereby improve symptoms. Subjects with OCD or TS were treated with active rTMS to the supplementary motor area (SMA) for 10 daily sessions at 1 Hz, 100% of motor threshold, 1200 stimuli/day. Suggestions of clinical improvement were apparent as early as the first week of rTMS. At the second week of treatment, statistically significant reductions were seen in the YBOCS, YGTSS, CGI, HARS, HDRS, SAD, BDI, SCL-90, and SASS. Symptoms improvement was correlated with a significant increase of the right resting motor threshold and was stable at 3 months follow-up. Slow rTMS to SMA resulted in a significant clinical improvement and a normalization of the right hemisphere hyperexcitability, thereby restoring hemispheric symmetry in motor threshold

Incidenza della sclerosi multipla in Toscana: uno studio basato su dati amministrativi

INTRODUZIONE L’Italia è un’area ad elevato rischio di sclerosi multipla (SM) con una prevalenza stimata di 110.000 casi e un’incidenza di 3.400 casi annui [1]. Gli ultimi dati pubblicati sulla prevalenza sono 149 casi su 100.000 a Genova nel 2007 [2], 140 casi a Padova nel 2009 [3] e 210 nella parte meridionale della Sardegna nel 2007 [4]. Per quanto riguarda l’incidenza, i dati più recenti sono 5,5 casi su 100.000 a Padova nel periodo 2000-09 [3], 6,6 a Genova nel 1998-2007 [2], e 9,7 in Sardegna nel 2003-07 [4]. Dallo scorso anno è stato attivato in Italia un registro nazionale di SM il quale rappresenterà, nel prossimo futuro, un valido strumento per lo studio dell’epidemiologia di questa malattia. Anche in Toscana è presente, dal 2006, un registro regionale della SM ma, al momento, non è rappresentativo dell’intera popolazione di pazienti. Una possibile alternativa per studiare l’epidemiologia è attraverso i dati amministrativi. Questi, infatti, coprono l’intera popolazione residente e vengono raccolti di routine in un modo standardizzato ai fini della gestione del servizio sanitario. In un precedente lavoro, abbiamo creato e validato un algoritmo di cattura dei casi prevalenti basato su fonti amministrative [5]. La prevalenza, calcolata al 2011, è risultata pari a 188 casi per 100.000 [5]. Anche altre Regioni hanno utilizzato i dati amministrativi per stimare la prevalenza della SM, come il Lazio con 131 casi su 100.000 nel 2011 [6], la Puglia con 183 casi nel 2012, il Veneto con 170-180 casi nel 2015, la Sicilia con 110 casi nel 2010 e la Sardegna con 360 casi nel 2016 [1]. OBIETTIVI Calcolare l’incidenza della SM in Toscana utilizzando dati amministrativi. METODI Per il calcolo dell’incidenza abbiamo creato il seguente algoritmo: ospedalizzazione in reparto per acuti e con diagnosi primaria di SM, esenzione attiva per SM, e prescrizione di farmaci specifici. I casi incidenti sono stati identificati come quei casi catturati dall’algoritmo non tracciati in precedenza nei flussi amministrativi, e la data della prima traccia è stata considerata quale data di diagnosi della SM. Da questa coorte di soggetti abbiamo selezionato i pazienti con un’età ≤ 55 anni, residenti in Toscana al momento della diagnosi e presenti in anagrafe da almeno 10 anni (o nati in Toscana se età <10). Abbiamo calcolato i tassi grezzi e standardizzati e gli intervalli di confidenza (IC) al 95% per gli anni 2011-2015. RISULTATI Abbiamo identificato, dal 2011 al 2015, 1.056 nuovi casi in Toscana con un’incidenza che varia da 5,04 nel 2011 a 6,02 casi su 100.000 nel 2015 (Tabella 1). Nelle donne l’incidenza è circa due volte più alta rispetto agli uomini con un range che va da 6,48 nel 2011 a 7,96 su 100.000 nel 2015 nelle donne, e da 3,49 nel 2011 a 3,93 nel 2015 negli uomini (Tabella 2). Prendendo in considerazione l’ultimo anno di analisi (2015), abbiamo inoltre osservato delle differenze per ASL di residenza al momento della diagnosi, con aree in cui il tasso di incidenza è inferiore alla media regionale, come Grosseto (4,58), Pisa (4,33 casi/100.000), Siena (3,30), Lucca (3,07) e Viareggio (3,06), e aree in cui l’incidenza è più elevata rispetto alla media, come Empoli (7,99), Livorno (8,80) e Arezzo (9,78)

Prevalence of chronic comorbidities in people with multiple sclerosis: descriptive study based on administrative data in Tuscany (Central Italy)

Objective Chronic comorbidities are common in people with multiple sclerosis (PwMS), thus worsening their prognosis and quality of life, and increasing disease burden. The aim of the present study was to evaluate the prevalence of common comorbidities in PwMS in Tuscany (Central Italy) and to compare it with the general population. Methods The prevalence of comorbidities, including diabetes, chronic obstructive pulmonary disease (COPD), hypertension, stroke, heart failure (HF), cardiac infarction and ischemic heart disease (IHD), was assessed in PwMS and in general population resident in Tuscany, aged &gt; 20 years, using administrative data. Results In total, we identified 8,274 PwMS. Among them, 34% had at least one comorbidity, with hypertension being the most common (28.5%). Comparing PwMS with the general population, PwMS had a higher frequency of hypertension and stroke when considering the whole group, and of diabetes, COPD, and IHD when considering sex and age subgroups. This increased risk was especially evident in the young and intermediate age groups, where multiple sclerosis may play an important role as risk factor for some comorbidities. In PwMS, as well as in the general population, prevalence of chronic diseases was higher in males and increased with age. Conclusions Comorbidities frequently coexist with multiple sclerosis and they may have an impact on this complex disease, from the health, clinical, and socioeconomic points of view. Therefore, a routine screening of chronic comorbidities should be a crucial step in clinical practice, as well as the promotion of healthy lifestyles to prevent the onset and to reduce their burden

Increasing prevalence of multiple sclerosis in Tuscany: a study based on validated administrative data

AIMS Italy is a high-risk area for Multiple Sclerosis (MS) with a prevalence of around 140/105 (2009) with the exception of Sardinia, with about 224 cases/105 (2009). Nowadays, in Italy, prevalence is absolutely higher than the above estimates. Indeed, prevalence is rising due to annual incidence that is higher than annual mortality. In Tuscany a population MS register has been founded but, to date, it’s not yet completed. To monitor disease epidemiology, comorbidities and care pathways, but also to describe the disease burden and to plan its prevention, treatment and management strategies and resource allocation, population-based studies are preferable. Administrative data offer a unique opportunity for population-based prevalence study of chronic diseases such as MS. Our aim is to update the prevalence of MS in Tuscany and to demonstrate its progressive increment. METHODS The prevalence was calculated using a case-finding algorithm based on administrative data: hospitalization, specific MS drug dispensing, disease-specific exemptions from patient copayment, home and residential long-term care and inhabitant registry. To test algorithm sensitivity, we used a true-positive reference cohort of 302 MS patients from the Tuscan MS register. To test algorithm specificity, we used a general population cohort of 2,644,094 individuals who were presumably not affected by MS (who had never effectuated either cranial or spinal cord CT scan or MRI and had never received a neurological outpatient visit within the NHS). We calculated prevalence on three consecutive years (2011, 2012, 2013). RESULTS At prevalence date (31 December), we identified 6,890 cases in 2011, 7,057 in 2012 and 7,330 in 2013 with a rate of 187.9, 191.1 and 195.4/105, respectively. The female:male ratio slightly increased from 2.0 in 2011 to 2.1 in 2012-2013. The sensitivity of algorithm was 98% and its specificity was 99.99%. DISCUSSION We found a progressive increment of prevalence that confirmed our hypothesis of increasing prevalence. Although our validity study demonstrated a high level of sensibility, we could miss some patients, especially individuals with a severe MS, who did not access the healthcare system and who did not use the DMDs included in our algorithm. CONCLUSIONS We confirmed that Tuscany is a high-risk area for MS and that the prevalence is increasing over time. Despite some limitations, we also demonstrated that our algorithm can accurately identify patients and this cohort is suitable to monitor care pathways. Our future aim is to create an integrated dataset with administrative and clinical data from MS register

prospective study of clinical neurophysiological and urodynamic findings in multiple sclerosis patients undergoing percutaneous transluminal venous angioplasty

Abstract Objective Verify whether Percutaneous Transluminal Angioplasty (PTA) may affect neural conduction properties in Multiple Sclerosis (MS) patients, thereby modifying patients' disability, with prospective neurophysiological, urodynamic, clinical and subjective well-being evaluations. Methods In 55 out of 72 consecutively screened MS patients, the following procedures were carried out before (T0), at 2–6 months (T1) and at 6–15 months (T2) after a diagnostic phlebography, eventually followed by the PTA intervention if chronic cerebrospinal venous insufficiency (CCSVI) was diagnosed: clinical/objective evaluation (Expanded Disability Status Scale, EDSS), ratings of subjective well-being, evaluation of urodynamic functions and multimodal EPs (visual, acoustic, upper and lower limbs somatosensory and motor evoked potentials). Results The number of dropouts was relatively high, and a complete set of neurophysiological and clinical data remained available for 37 patients (19 for urological investigations). The subjective well-being score significantly increased at T1 and returned close to basal values at T2, but their degree of objective disability did not change. Nevertheless, global EP-scores (indexing the impairment in conductivity of central pathways in multiple functional domains) significantly increased from T0 (7.9 ± 6.0) to T1 (9.2 ± 6.3) and from T0 to T2 (9.8 ± 6.3), but not from T1 and T2 (p > 0.05). Neurogenic urological lower tract dysfunctions slightly increased throughout the study. Conclusions The PTA intervention did not induce significant changes in disability in the present cohort of MS patients, in line with recent evidence of clinical inefficacy of this procedure. Significance Absence of multimodal neurophysiological and functional testing changes in the first 15 months following PTA suggests that conduction properties of neural pathways are unaffected by PTA. Current findings suggest that the short-lived (2–6 months), post-PTA, beneficial effect on subjective well-being measures experienced by MS patients is likely related to a placebo effect

Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?

Background and purpose: Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses.Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS.Results: Four hundred seventy-three pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95% confidence interval [CI]=14.3-100.0, p &lt; 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95% CI=8.3-50.0, p &lt; 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95% CI = 1.2-4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab and ocrelizumab showed a 2.3-fold lower gain (95% CI = 1.4-3.8, p=0.001), whereas those on fingolimod showed a 1.7-fold higher gain (95% CI = 1.1-2.7, p = 0.012), compared to patients treated with other DMTs.Conclusions: All pwMS increased their serum SARS-CoV-2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (&gt;659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff

The Role of the Substantia Nigra Pars Compacta in Regulating Sleep Patterns in Rats

Background. As of late, dopaminergic neurotransmission has been recognized to be involved in the generation of sleep disturbances. Increasing evidence shows that sleep disturbances in Parkinson's disease (PD) patients are mostly related to the disease itself, rather than being a secondary phenomenon. Evidence contained in the literature lends support to the hypothesis that the dopaminergic nigrostriatal pathway is closely involved in the regulation of sleep patterns. Methodology/Principal Findings. To test this hypothesis we examined the electrophysiological activity along the sleep-wake cycle of rats submitted to a surgically induced lesion of the SNpc by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We demonstrated that a 50% lesion of the substantia nigra pars compacta (SNpc) suffices to produce disruptions of several parameters in the sleep-wake pattern of rats. A robust and constant decrease in the latency to the onset of slow wave sleep (SWS) was detected throughout the five days of recording in both light [F((22.16)) = 72.46, p<0.0001] and dark [F((22.16)) = 75.0, p<0.0001] periods. Also found was a pronounced increase in the percentage of sleep efficiency during the first four days of recording [F((21.15)) = 21.48, p<0.0001], in comparison to the sham group. Additionally, the reduction in the SNpc dopaminergic neurons provoked an ablation in the percentage of rapid eye movement sleep (REM) during three days of the sleep-wake recording period with a strong correlation (r = 0.91; p<0.0001) between the number of dopaminergic neurons lost and the percentage decrease of REM sleep on the first day of recording. On day 4, the percentage of REM sleep during the light and dark periods was increased, [F((22.16)) = 2.46, p<0.0007], a phenomenon consistent with REM rebound. Conclusions/Significance. We propose that dopaminergic neurons present in the SNpc possess a fundamental function in the regulation of sleep processes, particularly in promoting REM sleep.AFIPCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniv Fed Parana, Dept Farmacol, BR-80060000 Curitiba, Parana, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilFAPESP: 98/14.303-3Web of Scienc

Distinct Olfactory Cross-Modal Effects on the Human Motor System

BACKGROUND: Converging evidence indicates that action observation and action-related sounds activate cross-modally the human motor system. Since olfaction, the most ancestral sense, may have behavioural consequences on human activities, we causally investigated by transcranial magnetic stimulation (TMS) whether food odour could additionally facilitate the human motor system during the observation of grasping objects with alimentary valence, and the degree of specificity of these effects. METHODOLOGY/PRINCIPAL FINDINGS: In a repeated-measure block design, carried out on 24 healthy individuals participating to three different experiments, we show that sniffing alimentary odorants immediately increases the motor potentials evoked in hand muscles by TMS of the motor cortex. This effect was odorant-specific and was absent when subjects were presented with odorants including a potentially noxious trigeminal component. The smell-induced corticospinal facilitation of hand muscles during observation of grasping was an additive effect which superimposed to that induced by the mere observation of grasping actions for food or non-food objects. The odour-induced motor facilitation took place only in case of congruence between the sniffed odour and the observed grasped food, and specifically involved the muscle acting as prime mover for hand/fingers shaping in the observed action. CONCLUSIONS/SIGNIFICANCE: Complex olfactory cross-modal effects on the human corticospinal system are physiologically demonstrable. They are odorant-specific and, depending on the experimental context, muscle- and action-specific as well. This finding implies potential new diagnostic and rehabilitative applications

Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Introduction Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked.This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register.MethodsThe Register collects, through a standardized Web-based Application, unique patients.Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated.ResultsThe Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients.The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000-2015) to 60% (enrolment period 2016-2022). In the cohort of patients registered after 2016, there were &gt;= 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2).Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months.ConclusionsData from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon