Publications by authors named "Antonella Conte"

119 Publications

Importance of broth-enrichment culture in equine endometritis diagnosis.

New Microbiol 2021 Jan 14;44(1):19-23. Epub 2021 Jan 14.

Department of Veterinary Medicine and Animal Production, Via Delpino 1, University of Naples "Federico II", Naples, Italy.

The objective of this study was to investigate the diagnostic accuracy of the standard microbiological protocol to assure the evaluation of bacterial endometritis in the equine clinical practice. Four hundred fifty-two equine uterine swabs were seeded on different types of agar plates and then in a broth-enrichment (Brain Heart Infusion Broth) before plating by using the same media the day after. The prevalence of positivity was 33.7% following direct plating and 66.3% following use of added enrichment-broth phase before seeding on solid media. Furthermore, the prevalence of isolated bacteria included E. coli (29.7%) and Streptococcus equi subsp. zooepidemicus (15.2%), both frequently associated with equine endometritis. Our results indicate that the addition enrichment-broth culture significantly increases the rate of positivity for the detection of bacteria in equine uterine swabs compared to the direct plating of samples alone. Thus, this diagnostic technique may be recommended to increase the sensitivity of bacteriological analysis in mares with endometritis.
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January 2021

The efficacy of rehabilitation in people with Guillain-Barrè syndrome: a systematic review of randomized controlled trials.

Expert Rev Neurother 2021 Feb 23:1-7. Epub 2021 Feb 23.

Department of Human Neurosciences, Sapienza University of Rome, Viale Dell' Università, Rome, Italy.

Introduction: Individuals with Guillain-Barrè syndrome (GBS) showed significant longer-term psychological sequelae, due to persistent disability. In recent years, great advances have been made in medical care for patients with GBS. However, the focus has been mainly on patient care in the acute phase and improving survival instead of long-term disability. The purpose of this study was to evaluate the efficacy of rehabilitation in people with GBS through a systematic review of randomized controlled trials.

Area Covered: PRISMA guidelines were used to perform this systematic review. Six bibliographic databases were searched: PUBMED, WEB OF SCIENCE, PEDro, CINHAL, PSYCHINFO, and SCOPUS. Papers included in the systematic review should have a search design of a randomized controlled trial. The quality of the clinical trials included was evaluated according to Jadad score.

Expert Opinion: After eliminating duplicates, 472 records got screened, three RCTs were included in the systematic review. Overall, the analysis of the three randomized controlled trials showed that various types of rehabilitation interventions are correlated to an improvement in the patient's well-being. Finally, it is not possible to extrapolate definite conclusions on the effectiveness of rehabilitation treatment in patients with GBS. Therefore, high-quality future studies are needed to confirm these hypotheses.
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http://dx.doi.org/10.1080/14737175.2021.1890034DOI Listing
February 2021

Operationalization of a frailty index in patients with multiple sclerosis: A cross-sectional investigation.

Mult Scler 2021 Feb 10:1352458520987541. Epub 2021 Feb 10.

Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy/IRCCS Neuromed, Pozzilli, Italy.

Background: Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical complexity of patients with multiple sclerosis (MS).

Objective: To investigate the relationship between frailty and the clinical manifestations of MS.

Methods: Patients with MS were consecutively enrolled at five tertiary dedicated services. Disability and fatigue were assessed. The phenotypes of MS were also identified. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits.

Results: Overall, 745 MS patients (mean age = 48.2 years, standard deviation = 11.7 years; women 68%) were considered. The median FI value was 0.12 (interquartile range = 0.05-0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype.

Conclusion: Frailty is significantly associated with major characteristics of MS. The findings of the present cross-sectional investigation should be explored in future longitudinal studies.
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http://dx.doi.org/10.1177/1352458520987541DOI Listing
February 2021

Prokaryotic Diversity and Metabolically Active Communities in Brines from Two Perennially Ice-Covered Antarctic Lakes.

Astrobiology 2021 Feb 1. Epub 2021 Feb 1.

Dipartimento di Scienze Teoriche e Applicate, University of Insubria, Varese, Italy.

The genomic diversity of bacteria and archaea in brines (BC1, BC2, and BC3) from two adjacent and perennially frozen Antarctic lakes (L16 and L-2) in the Boulder Clay (BC) area was investigated together with the metabolically active fraction of both communities, by analyzing the bulk rRNA as a general marker of metabolic activity. Although similar bacterial and archaeal assemblages were observed at phylum level, differences were encountered when considering the distribution in species. Overall, the total bacterial communities were dominated by Bacteroidetes. A massive occurrence of flavobacterial sequences was observed within the metabolically active bacterial communities of the BC1 brine, whereas the active fractions in BC2 and BC3 strongly differed from the bulk communities being dominated by Betaproteobacteria (mainly members). The BC lakes also hosted sequences of the most thermally tolerant archaea, also related to well-known hyperthermophiles. Interestingly, RNA sequences of the hyperthermophilic genus were retrieved in all brine samples. Finally, a high abundance of the strictly anaerobic methanogens (such as members) within the active community suggests that anoxic conditions might occur in the lake brines. Our findings indicate perennially ice-covered Antarctic lakes as plausible terrestrial candidates for the study of the potential for extant life on different bodies of our solar system.
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http://dx.doi.org/10.1089/ast.2020.2238DOI Listing
February 2021

Outcome measures for physical fatigue in individuals with multiple sclerosis: a systematic review.

Expert Rev Pharmacoecon Outcomes Res 2021 Jan 28. Epub 2021 Jan 28.

Department of Human Neurosciences, Sapienza University of Rome , Piazzale Aldo Moro 5, 00185, Rome, Italy.

Introduction: : Physical fatigue can be a common reason for early retirement or sick leave since it appears in the earliest stages of multiple sclerosis (MS). Therefore, a prompt and accurate diagnosis is essential. This systematic review aims to identify and describe the instruments used to assess physical fatigue in MS patients with consideration for the languages used to validate the instruments and their methodological qualities.

Area Covered: : This study has been carried out through "Medline," "Scopus," "Cinhal," and "Web of Science" databases for all the papers published before January 24, 2020. Three independent authors have chosen the eligible studies based upon pre-set criteria of inclusion. Data collection, data items, and assessment of the risk of bias: the data extraction approach was chosen based on the Cochrane Methods. For data collection, the authors followed the recommendations from the COSMIN initiative. Study quality and risk of bias were assessed using the COSMIN Check List.

Expert Opinion: : 119 publications have been reviewed. The 45 assessment scales can be divided into specific scales for physical fatigue and specific scales for MS. The most popular tools are the Fatigue Severity Scale and the Modified Fatigue Impact Scale.
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http://dx.doi.org/10.1080/14737167.2021.1883430DOI Listing
January 2021

Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis.

J Neurol 2021 Jan 26. Epub 2021 Jan 26.

Multiple Sclerosis Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy.

Background: Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5-10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce.

Objectives: To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption.

Methods: Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II-III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm.

Results: Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II-III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery.

Conclusion: ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.
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http://dx.doi.org/10.1007/s00415-021-10412-0DOI Listing
January 2021

Neuroimaging in idiopathic adult-onset focal dystonia.

Neurol Sci 2021 Jan 3. Epub 2021 Jan 3.

Department of Medical Science and Public Health, Institute of Neurology, University of Cagliari, Cagliari, Italy.

We aimed to study the attitude of Italian neurologists in the use of conventional MRI in patients with idiopathic adult-onset focal dystonia. Patients were included in the Italian Dystonia Registry by experts working in different Italian centers. MRI was available for 1045 of the 1471 (71%) patients included in the analysis. Using logistic regression analysis, we found that MRI was more likely to be performed in patients with cervical dystonia, spasmodic dysphonia, or non-task-specific upper limb dystonia, whereas it was less likely to be performed in patients with blepharospasm or task-specific upper limb dystonia. We did not find differences in the number of MRIs performed between neurological centers in Northern, Central, and Southern Italy. We conclude that although the diagnosis of idiopathic adult-onset dystonia is mainly based on clinical grounds, many movement disorder experts rely on MRI to confirm a diagnosis of idiopathic dystonia. We suggest that neuroimaging should be used in patients with adult-onset focal dystonia to rule out secondary forms.
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http://dx.doi.org/10.1007/s10072-020-05025-wDOI Listing
January 2021

Defective Somatosensory Inhibition and Plasticity Are Not Required to Develop Dystonia.

Mov Disord 2020 Dec 17. Epub 2020 Dec 17.

Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, United Kingdom.

Background: Dystonia may have different neuroanatomical substrates and pathophysiology. This is supported by studies on the motor system showing, for instance, that plasticity is abnormal in idiopathic dystonia, but not in dystonia secondary to basal ganglia lesions.

Objective: The aim of this study was to test whether somatosensory inhibition and plasticity abnormalities reported in patients with idiopathic dystonia also occur in patients with dystonia caused by basal ganglia damage.

Methods: Ten patients with acquired dystonia as a result of basal ganglia lesions and 12 healthy control subjects were recruited. They underwent electrophysiological testing at baseline and after a single 45-minute session of high-frequency repetitive somatosensory stimulation. Electrophysiological testing consisted of somatosensory temporal discrimination, somatosensory-evoked potentials (including measurement of early and late high-frequency oscillations and the spatial inhibition ratio of N20/25 and P14 components), the recovery cycle of paired-pulse somatosensory-evoked potentials, and primary motor cortex short-interval intracortical inhibition.

Results: Unlike previous reports of patients with idiopathic dystonia, patients with acquired dystonia did not differ from healthy control subjects in any of the electrophysiological measures either before or after high-frequency repetitive somatosensory stimulation, except for short-interval intracortical inhibition, which was reduced at baseline in patients compared to control subjects.

Conclusions: The data show that reduced somatosensory inhibition and enhanced cortical plasticity are not required for the clinical expression of dystonia, and that the abnormalities reported in idiopathic dystonia are not necessarily linked to basal ganglia damage. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28427DOI Listing
December 2020

Correction to: The Use of Botulinum Toxin for Treatment of the Dystonias.

Handb Exp Pharmacol 2021 ;263:285

Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1007/164_2020_414DOI Listing
January 2021

Is somatosensory temporal discrimination threshold a biomarker of disease progression in multiple sclerosis?

Clin Neurophysiol 2020 Dec 13;131(12):2935-2936. Epub 2020 Oct 13.

Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy; IRCCS Neuromed, Pozzilli, IS, Italy.

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http://dx.doi.org/10.1016/j.clinph.2020.09.012DOI Listing
December 2020

Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors.

Mult Scler 2021 03 19;27(3):430-438. Epub 2020 Nov 19.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy.

Background: No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available.

Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA).

Methods: Relapsing-onset MS patients ( = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models.

Results: SPMS identified by the DDA ( = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability ( < 0.0001), than those identified by the ND ( = 3868, 20.0%). In both groups, the most consistent risk factors ( < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0.

Conclusion: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.
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http://dx.doi.org/10.1177/1352458520974366DOI Listing
March 2021

Development of a Clinical Rating Scale for the Severity of Apraxia of Eyelid Opening, Either Isolated or Associated with Blepharospasm.

Mov Disord Clin Pract 2020 Nov 22;7(8):950-954. Epub 2020 Sep 22.

Department of Medical Sciences and Public Health, Institute of Neurology University of Cagliari and AOU-Cagliari Cagliari Italy.

Background: Apraxia of eyelid opening is a movement disorder characterized by an inability to raise the eyelids without any overt contractions of the orbicularis oculi muscle. There is currently no clinical scale to rate the severity of this condition.

Objectives: To develop and validate a novel scale that considers phenomenological aspects relevant to the severity of the condition.

Methods: The study sample included 20 patients with apraxia of eyelid opening, either isolated (9 patients) or associated with blepharospasm (11 patients). To validate the scale, selected features were checked for reliability, reliable items were combined to generate the scale, and clinimetric properties were evaluated.

Results: The novel severity scale yielded acceptable reliability, scaling assumptions, internal consistency, and sensitivity to change; a lack of floor and ceiling effects; and no correlation with the blepharospasm severity rating scale.

Conclusions: We propose a severity scale that considers the most relevant apraxia of eyelid opening motor abnormalities based on objective criteria. This scale can be reliably administered by general neurologists after a brief training.
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http://dx.doi.org/10.1002/mdc3.13083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604665PMC
November 2020

Isolated head tremor: A DAT-SPECT and somatosensory temporal discrimination study.

Parkinsonism Relat Disord 2020 12 9;81:56-59. Epub 2020 Oct 9.

Department of Human Neuroscience, Sapienza University of Rome, Viale Dell'Università 30, 00185, Rome, Italy; IRCCS NEUROMED, Via Atinense 18, 86077, Pozzilli, Italy. Electronic address:

Introduction: To better understand the pathophysiology of isolated head tremor, we investigated somatosensory temporal discrimination threshold (STDT) and dopaminergic neurotransmission with I-FP-CIT (DAT-SPECT) in patients with isolated head tremor, as well as potential correlations with their clinical features.

Methods: We enrolled 14 patients with isolated head tremor who underwent clinical examination, STDT testing, and DAT-SPECT.

Results: We found normal radiotracer uptake in both striata as assessed with DAT-SPECT examination, but higher STDT values in patients as compared to healthy subjects. No significant correlations emerged between STDT values, specific binding ratios of radiotracer uptake, and demographic or clinical features.

Conclusion: Our study found normal radiotracer uptake with DAT-SPECT examination, suggesting dopaminergic neurotransmission integrity in patients with isolated head tremor. Patients with isolated head tremor exhibited an abnormally elevated STDT. Both results support the hypothesis that isolated head tremor should be considered a form of dystonia.
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http://dx.doi.org/10.1016/j.parkreldis.2020.10.015DOI Listing
December 2020

Investigating the effects of transcranial alternating current stimulation on primary somatosensory cortex.

Sci Rep 2020 10 13;10(1):17129. Epub 2020 Oct 13.

IRCCS NEUROMED, Via Atinense, 18, 86077, Pozzilli, IS, Italy.

Near-threshold tactile stimuli perception and somatosensory temporal discrimination threshold (STDT) are encoded in the primary somatosensory cortex (S1) and largely depend on alpha and beta S1 rhythm. Transcranial alternating current stimulation (tACS) is a non-invasive neurophysiological technique that allows cortical rhythm modulation. We investigated the effects of tACS delivered over S1 at alpha, beta, and gamma frequencies on near-threshold tactile stimuli perception and STDT, as well as phase-dependent tACS effects on near-threshold tactile stimuli perception in healthy subjects. In separate sessions, we tested the effects of different tACS montages, and tACS at the individualised S1 μ-alpha frequency peak, on STDT and near-threshold tactile stimuli perception. We found that tACS applied over S1 at alpha, beta, and gamma frequencies did not modify STDT or near-threshold tactile stimuli perception. Moreover, we did not detect effects of tACS phase or montage. Finally, tACS did not modify near-threshold tactile stimuli perception and STDT even when delivered at the individualised μ-alpha frequency peak. Our study showed that tACS does not alter near-threshold tactile stimuli or STDT, possibly due to the inability of tACS to activate deep S1 layers. Future investigations may clarify tACS effects over S1 in patients with focal dystonia, whose pathophysiology implicates increased STDT.
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http://dx.doi.org/10.1038/s41598-020-74072-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553944PMC
October 2020

The Pathophysiological Correlates of Parkinson's Disease Clinical Subtypes.

Mov Disord 2021 02 10;36(2):370-379. Epub 2020 Oct 10.

IRCCS Neuromed, Pozzilli, Italy.

Background: Possible pathophysiological mechanisms underlying Parkinson's disease (PD) clinical subtypes are unknown. The objective of this study was to identify pathophysiological substrate of PD subtypes using neurophysiological techniques.

Methods: One hundred de novo PD patients participated. We collected patient demographic and clinical data, which were used to perform a hierarchical cluster analysis. The neurophysiological assessment tested primary motor cortex excitability and plasticity using transcranial magnetic stimulation. To evaluate motor performance, we performed a kinematic analysis of fast index finger abduction. To investigate sensory function and sensorimotor mechanisms, we measured the somatosensory temporal discrimination threshold at rest and during movement, respectively.

Results: Hierarchical cluster analysis identified 2 clinical clusters. Cluster I ("mild motor-predominant") included patients who had milder motor and nonmotor symptoms severity than cluster II patients, who had a combination of severe motor and nonmotor manifestations (diffuse malignant). We observed that the diffuse malignant subtype had increased cortical excitability and reduced plasticity compared with the mild motor-predominant subtype. Kinematic analysis of motor performance demonstrated that the diffuse malignant subtype was significantly slower than the mild motor-predominant subtype. Conversely, we did not observe any significant differences in sensory function or sensorimotor integration between the two PD subtypes.

Conclusions: De novo PD subtypes showed different patterns of motor system dysfunction, whereas sensory function and sensorimotor integration mechanisms did not differ between subtypes. Our findings suggest that the subtyping of PD patients is not a mere clinical classification but reflects different pathophysiological mechanisms. Neurophysiological parameters may represent promising biomarkers to evaluate PD subtypes and their progression. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28321DOI Listing
February 2021

The peripheral blood immune cell profile in a teriflunomide-treated multiple sclerosis patient with COVID-19 pneumonia.

J Neuroimmunol 2020 Jul 15;346:577323. Epub 2020 Jul 15.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185, Rome, Italy.

A teriflunomide-treated multiple sclerosis patient with COVID-19 pneumonia was hospitalized and recovered in 15 days. The immunophenotyping analysis of peripheral blood cells was performed in two time points: the first was 1 month before (pre-infection) while the second was during COVID-19 pneumonia (infection). At the infection time point, no differences in the percentages of immune activation and immunesenescence of CD4+ and CD8+ T-cells were observed compared to the pre-infection time point. Our evaluation seems to confirm that teriflunomide controls T-cells immune activation and immunosenescence suggesting that teriflunomide should not be discontinued in MS patients with an active COVID-19 pneumonia.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361089PMC
July 2020

Awareness of Dystonic Posture in Patients With Cervical Dystonia.

Front Psychol 2020 23;11:1434. Epub 2020 Jun 23.

Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.

Background: Cervical dystonia (CD) is a focal dystonia characterized by sensorimotor integration abnormalities and proprioceptive dysfunction. Since proprioception is essential for bodily awareness, we hypothesized that CD patients may have an impairment in dystonic posture awareness. More information on this issue could be useful to better understand whether dystonic posture affects bodily perception in CD and could help in the development of specific rehabilitation strategies based on proprioceptive input manipulation to restore bodily awareness.

Objectives: The aim of our study was to investigate dystonic posture and head tremor awareness in CD patients by comparing evaluations performed by CD patients with those performed by a neurologist expert in movement disorders.

Methods: We enrolled 25 CD patients. We investigated dystonic posture and head tremor awareness in CD patients using a standardized protocol in which patients were asked to describe the type of dystonic pattern, both while viewing standardized images of different CD subtypes (torticollis, laterocollis, anterocollis, and retrocollis) and after watching a video recording of their dystonic posture and head tremor.

Results: We found that 72% of CD patients correctly recognized their dystonic posture when viewing standardized images, whereas 84% of CD patients were able to identify their dystonic pattern when watching a video recording of themselves. CD patients also displayed a preserved awareness of their head tremor. We did not find any associations between dystonic pattern awareness and clinical or demographic features.

Conclusion: Contrary to our hypothesis, the majority of CD patients have a preserved awareness of their dystonic pattern and tremor.
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http://dx.doi.org/10.3389/fpsyg.2020.01434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324713PMC
June 2020

Validity and reliability of the 12-item Berg Balance Scale in an Italian population with Parkinson's disease: A cross sectional study.

Arq Neuropsiquiatr 2020 07 8;78(7):419-423. Epub 2020 Jun 8.

Ospedale Pediatrico Bambino Gesù, Dipartimento di Neuroscienze e Neuroriabilitazione, Unità di Neuroriabilitazione, Fiumicino, RM, Italy.

Background: The Berg Balance Scale is widely used to measure balance ability in clinical practice. Recently, the original version was redefined from 14 into 12 items. Its psychometric properties were investigated for different populations. However, for Parkinson disease the new version has not been validated yet.

Objective: The purpose of the present study was to evaluate psychometric properties of the 12-item Berg Balance Scale (BBS-12) in a population with Parkinson disease.

Methods: Internal consistency was evaluated with Cronbach's alpha coefficient, whereas reliability was assessed with the intraclass correlation coefficient. For validity analysis, the Pearson correlation coefficient of the BBS-12 was evaluated with the Tinetti Scale and the Physical Activity Scale for the Elderly.

Results: The BBS-12 was applied to 50 individuals with a mean age of 65.6 years (SD 11.8). The internal consistency showed a good value (Cronbach's alpha 0.886) and reproducibility reveled very high performances for both inter-rater and intra-rater reliabilities (ICC 0.987 and 0.986, respectively). The validity study demonstrated good linear correlation with the Tinetti Scale (p<0.01) and with the Sport and Home Subscales of the Physical Activity Scale for the Elderly (p<0.01).

Conclusions: The present findings revealed the BBS-12 as a reliable and valid assessment tool to measure balance ability in Parkinson disease. Italian health professionals can now use it with more confidence.
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http://dx.doi.org/10.1590/0004-282X20200030DOI Listing
July 2020

Early diagnosis of secondary progressive multiple sclerosis: focus on fluid and neurophysiological biomarkers.

J Neurol 2020 Jun 5. Epub 2020 Jun 5.

Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.

Background And Aims: Most patients with multiple sclerosis presenting with a relapsing-remitting disease course at diagnosis transition to secondary progressive multiple sclerosis (SPMS) 1-2 decades after onset. SPMS is characterized by predominant neurodegeneration and atrophy. These pathogenic hallmarks result in unsatisfactory treatment response in SPMS patients. Therefore, early diagnosis of SPMS is necessary for prompt treatment decisions. The aim of this review was to assess neurophysiological and fluid biomarkers that have the potential to monitor disease progression and support early SPMS diagnosis.

Methods: We performed a systematic review of studies that analyzed the role of neurophysiological techniques and fluid biomarkers in supporting SPMS diagnosis using the preferred reporting items for systematic reviews and meta-analyses statement.

Results: From our initial search, we selected 24 relevant articles on neurophysiological biomarkers and 55 articles on fluid biomarkers.

Conclusion: To date, no neurophysiological or fluid biomarker is sufficiently validated to support the early diagnosis of SPMS. Neurophysiological measurements, including short interval intracortical inhibition and somatosensory temporal discrimination threshold, and the neurofilament light chain fluid biomarker seem to be the most promising. Cross-sectional studies on an adequate number of patients followed by longitudinal studies are needed to confirm the diagnostic and prognostic value of these biomarkers. A combination of neurophysiological and fluid biomarkers may be more sensitive in detecting SPMS conversion.
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http://dx.doi.org/10.1007/s00415-020-09964-4DOI Listing
June 2020

Cultivable Bacterial Communities in Brines from Perennially Ice-Covered and Pristine Antarctic Lakes: Ecological and Biotechnological Implications.

Microorganisms 2020 May 29;8(6). Epub 2020 May 29.

Dipartimento di Scienze Teoriche e Applicate, University of Insubria, 21100 Varese, Italy.

The diversity and biotechnological potentialities of bacterial isolates from brines of three Antarctic lakes of the Northern Victoria Land (namely Boulder Clay and Tarn Flat areas) were first explored. Cultivable bacterial communities were analysed mainly in terms of bacterial response to contaminants (i.e., antibiotics and heavy metals) and oxidation of contaminants (i.e., aliphatic and aromatic hydrocarbons and polychlorobiphenyls). Moreover, the biosynthesis of biomolecules (antibiotics, extracellular polymeric substances and enzymes) with applications for human health and environmental protection was assayed. A total of 74 and 141 isolates were retrieved from Boulder Clay and Tarn Flat brines, respectively. Based on 16S rRNA gene sequence similarities, bacterial isolates represented three phyla, namely Proteobacteria (i.e., Gamma- and Alphaproteobacteria), Bacteroidetes and Actinobacteria, with differences encountered among brines. At genus level, , , and members were dominant. Results obtained from this study on the physiological and enzymatic features of cold-adapted isolates from Antarctic lake brines provide interesting prospects for possible applications in the biotechnological field through future targeted surveys. Finally, findings on contaminant occurrence and bacterial response suggest that bacteria might be used as bioindicators for tracking human footprints in these remote polar areas.
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http://dx.doi.org/10.3390/microorganisms8060819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355736PMC
May 2020

Botulinum Toxin Effects on Sensorimotor Integration in Focal Dystonias.

Toxins (Basel) 2020 04 25;12(5). Epub 2020 Apr 25.

IRCCS NEUROMED, Via Atinense, 18, 86077 Pozzilli (IS), Italy.

(1) Background: In dystonia, the somatosensory temporal discrimination threshold (STDT) is abnormally increased at rest and higher and longer-lasting during movement execution in comparison with healthy subjects (HS), suggesting an abnormal sensorimotor integration. These abnormalities are thought to depend on abnormal proprioceptive input coming from dystonic muscles. Since Botulinum toxin-A (BT-A) reduces proprioceptive input in the injected muscles, our study investigated the effects of BT-A on STDT tested at rest and during voluntary movement execution in patients with focal dystonia. (2) Methods: We enrolled 35 patients with focal dystonia: 14 patients with cervical dystonia (CD), 11 patients with blepharospasm (BSP), and 10 patients with focal hand dystonia (FHD); and 12 age-matched HS. STDT tested by delivering paired stimuli was measured in all subjects at rest and during index finger abductions. (3) Results: Patients with dystonia had higher STDT values at rest and during movement execution than HS. While BT-A did not modify STDT at rest, it reduced the abnormal values of STDT during movement in CD and FHD patients, but not in BSP patients. (4) Conclusions: BT-A improved abnormal sensorimotor integration in CD and FHD, most likely by decreasing the overflow of proprioceptive signaling from muscle dystonic activity to the thalamus.
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http://dx.doi.org/10.3390/toxins12050277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290883PMC
April 2020

Advances in the pathophysiology of adult-onset focal dystonias: recent neurophysiological and neuroimaging evidence.

F1000Res 2020 30;9. Epub 2020 Jan 30.

Department of Human Neurosciences, Sapienza, University of Rome, Rome, Italy.

Focal dystonia is a movement disorder characterized by involuntary muscle contractions that determine abnormal postures. The traditional hypothesis that the pathophysiology of focal dystonia entails a single structural dysfunction (i.e. basal ganglia) has recently come under scrutiny. The proposed network disorder model implies that focal dystonias arise from aberrant communication between various brain areas. Based on findings from animal studies, the role of the cerebellum has attracted increased interest in the last few years. Moreover, it has been increasingly reported that focal dystonias also include nonmotor disturbances, including sensory processing abnormalities, which have begun to attract attention. Current evidence from neurophysiological and neuroimaging investigations suggests that cerebellar involvement in the network and mechanisms underlying sensory abnormalities may have a role in determining the clinical heterogeneity of focal dystonias.
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http://dx.doi.org/10.12688/f1000research.21029.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993830PMC
October 2020

Re-emergent Tremor in Parkinson's Disease: The Role of the Motor Cortex.

Mov Disord 2020 06 16;35(6):1002-1011. Epub 2020 Mar 16.

IRCCS NEUROMED, Pozzilli, Italy.

Background: Parkinson's disease patients may show a tremor that appears after a variable delay while the arms are kept outstretched (re-emergent tremor). The objectives of this study were to investigate re-emergent tremor pathophysiology by studying the role of the primary motor cortex in this tremor and making a comparison with rest tremor.

Methods: We enrolled 10 Parkinson's disease patients with both re-emergent and rest tremor. Tremor was assessed by spectral analysis, corticomuscular coherence and tremor-resetting produced by transcranial magnetic stimulation over the primary motor cortex. We also recorded transcranial magnetic stimulation-evoked potentials generated by motor cortex stimulation during rest tremor, tremor suppression during wrist extension, and re-emergent tremor. Spectral analysis, corticomuscular coherence, and tremor resetting were compared between re-emergent tremor and rest tremor.

Results: Re-emergent tremor showed significant corticomuscular coherence, causal relation between motor cortex activity and tremor muscle and tremor resetting. The P60 component of transcranial magnetic stimulation-evoked potentials reduced in amplitude during tremor suppression, recovered before re-emergent tremor, was facilitated at re-emergent tremor onset, and returned to values similar to those of rest tremor during re-emergent tremor. Compared with rest tremor, re-emergent tremor showed similar corticomuscular coherence and tremor resetting, but slightly higher frequency.

Conclusions: Re-emergent tremor is causally related with the activity of the primary motor cortex, which is likely a convergence node in the network that generates re-emergent tremor. Re-emergent tremor and rest tremor share common pathophysiological mechanisms in which the motor cortex plays a crucial role. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28022DOI Listing
June 2020

The effect of aquatic physical therapy on patients with multiple sclerosis: A systematic review and meta-analysis.

Mult Scler Relat Disord 2020 Jun 22;41:102022. Epub 2020 Feb 22.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome 00185, Italy. Electronic address:

Background: The aquatic environment has unique properties, such a buoyancy, turbulence, hydrostatic pressure, and resistance, which can be used to gain a range of exercise benefits. During the last decade, hydrotherapy has spread in a very heterogeneous rehabilitation field. However, the efficacy of this kind of rehabilitation is not clear in scientific literature. The purpose of this study is to conduct a systematic review with meta-analysis to evaluate the qualitative and quantitative results of physical therapy treatments in an aquatic setting for individuals with Multiple Sclerosis.

Method: PRISMA guidelines were used to carry out the systematic review and meta-analysis. Three bibliographic databases were searched: MEDLINE, PEDro, and the Cochrane Library. Papers included in the study have the following characteristics: (a) a randomized controlled trial design of research and (b) published in English. The quality of the clinical trials included were evaluated according to a Jadad score and through meta-analysis.

Results: After the elimination of duplicates, 116 records were screened. Among these, 11 Randomized Controlled Trials (RCTs) were included in the systematic review. Ten of these were involved in the meta-analysis. From the qualitative analysis, a larger number of studies were found with a high level of quality. Most of the results of the quantitative analysis were statistically significant (p< 0.05).

Conclusion: Aquatic physical therapy is a valid means of rehabilitation for people with Multiple Sclerosis. The integration of this methodological approach with conventional physical therapy is recommended. Nevertheless, more studies, a larger number of participants, and short-, medium-, and long-term follow-up are required to confirm current results.
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http://dx.doi.org/10.1016/j.msard.2020.102022DOI Listing
June 2020

Which is the best PML risk stratification strategy in natalizumab-treated patients affected by multiple sclerosis?

Mult Scler Relat Disord 2020 Jun 13;41:102008. Epub 2020 Feb 13.

Department of Public Health and Infectious Diseases, "Sapienza" University, P.le Aldo Moro, 5, 00185 Rome, Italy. Electronic address:

Background: The risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCPyV), is the main limitation to the use of natalizumab, highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Establishing the PML risk against expected benefits represents an obligatory requirement of MS treatment algorithm. In order to achieve this goal, the aims of this study were to establish if JCPyV-DNA detection and non-coding control region (NCCR) arrangements could play a role of biomarkers, supporting anti-JCPyV antibodies measurement, actually the only parameter for PML risk stratification.

Methods: Thirty RRMS patients in treatment with natalizumab were enrolled. Urine and blood samples were collected according to this calendar: baseline (T0), 4 (T1), 8 (T2), 12 (T3), 16 (T4), 20 months (T5) after beginning of natalizumab therapy. After JCPyV DNA extraction, a specific quantitative-PCR (Q-PCR) and arrangements' analysis of NCCR and Viral Capsid Protein 1 (VP1) were carried out.

Results: Q-PCR detected JCPyV DNA in urine and blood from baseline (T0) to 20 natalizumab infusions (T5), although JC viral load in urine was significantly higher compared to viremia, at all selected time points. A contextual analysis of the anti-JCPyV-antibodies versus JCPyV-DNA detection revealed that viral DNA preceded the antibodies' presence in the serum. During the first year of natalizumab treatment, sequences isolated from blood displayed an archetype JCPyV NCCR structure with the occurrence of point mutations, whereas after one year NCCR re-organizations were observed in plasma and PBMC with duplication of NF-1 binding site in box F, duplication of box C and partial or total deletion of box D. VP1 analysis showed the amino acid change mutation S269F in plasma and S267L in PBMC, involving the receptor-binding region of VP1. Phylogenetic analysis suggested a stability and a similarity across different isolates of the JCPyV VP1.

Conclusions: We highly recommend considering JCPyV-DNA detection and NCCR re-organizations as viral biomarkers in order to accurately identify JCPyV-infected patients with a specific humoral response not yet detectable and to identify NCCR arrangements correlated with the onset of neurovirulent variants.
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http://dx.doi.org/10.1016/j.msard.2020.102008DOI Listing
June 2020

JCPyV NCCR analysis in PML patients with different risk factors: exploring common rearrangements as essential changes for neuropathogenesis.

Virol J 2020 02 11;17(1):23. Epub 2020 Feb 11.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185, Rome, Italy.

Background: During severe immunosuppression or treatment with specific biological drugs, human polyomavirus JC (JCPyV) may establish a lytic infection in oligodendrocytes, leading to progressive multifocal leukoencephalopathy (PML). Beyond AIDS, which represents the most common predisposing condition, several biological drugs have been associated to the development of PML, such as natalizumab, fingolimod and dimethyl fumarate, which have been showed to increase the risk of PML in the multiple sclerosis (MS) population. JCPyV non-coding control region (NCCR) can be found in two different forms: a virulent neurotropic pathogenic form and a latent non-pathogenic form. The neurotropic forms contain a rearranged NCCR and are typically found in the cerebrospinal fluid, brain or blood of PML patients.

Case Presentation: We sequenced and critically examined JCPyV NCCR from isolates detected in the cerebrospinal fluid of four newly diagnosed progressive multifocal leukoencephalopathy patients: two HIV-positive and two HIV-negative multiple sclerosis patients. More complex NCCR rearrangements were observed in the two HIV-positive patients compared to the HIV-negative multiple sclerosis patients with PML.

Conclusions: The comparison of HIV-positive and HIV-negative MS patients with PML, allowed us to evidence the presence of a common pattern of JCPyV NCCR rearrangement, characterized by the deletion of the D-block, which could be one of the initial rearrangements of JCPyV NCCR needed for the development of PML.
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http://dx.doi.org/10.1186/s12985-020-1295-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014659PMC
February 2020

The Use of Botulinum Toxin for Treatment of the Dystonias.

Handb Exp Pharmacol 2021 ;263:107-126

Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.

Dystonias are characterized by involuntary muscle contractions, twisting movements, abnormal postures, and often tremor in various body regions. However, in the last decade several studies have demonstrated that dystonias are also characterized by sensory abnormalities. While botulinum toxin is the gold standard therapy for focal dystonia, exactly how it improves this disorder is not entirely understood. Neurophysiological studies in animals and humans have clearly demonstrated that botulinum toxin improves dystonic motor manifestations by inducing chemodenervation, therefore weakening the injected muscles. In addition, neurophysiological and neuroimaging evidence also suggests that botulinum toxin modulates the activity of various neural structures in the CNS distant from the injected site, particularly cortical motor and sensory areas. Concordantly, recent studies have shown that in patients with focal dystonias botulinum toxin ameliorates sensory disturbances, including reduced spatial discrimination acuity and pain. Overall, these observations suggest that in these patients botulinum toxin-induced effects encompass complex mechanisms beyond chemodenervation of the injected muscles.
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http://dx.doi.org/10.1007/164_2019_339DOI Listing
January 2021

Cortical M1 plasticity and metaplasticity in patients with multiple sclerosis.

Mult Scler Relat Disord 2020 Feb 5;38:101494. Epub 2019 Nov 5.

Department of Human Neurosciences, Sapienza, University of Rome, Viale dell' Università 30, 00185 Rome, Italy; IRCCS Neuromed, via Atinense 18, 86077 Pozzilli (IS), Italy. Electronic address:

Background: Previous studies on patients with Multiple Sclerosis (MS) have reported contrasting findings on cortical plasticity of the primary motor cortex and no study has yet evaluated the regulatory mechanisms of cortical plasticity (i.e., metaplasticity) in MS patients. The aim of the present study was to investigate primary motor cortex (M1) plasticity and metaplasticity in patients with MS.

Methods: Nineteen patients affected by Relapsing--Remitting MS (RR-MS) and 16 age- and sex-matched healthy controls underwent intermittent Theta Burst Stimulation (iTBS) to evaluate cortical plasticity and iTBS preceded by repetitive index finger movements to evaluate M1 metaplasticity.

Results: In healthy subjects MEP size significantly increased after iTBS whereas it significantly decreased when repetitive index finger movements preceded iTBS (metaplasticity) (factor PROTOCOL: p < 0.0001; PROTOCOL x TIME interaction: p = 0.001). Conversely, in MS patients MEP size mildly increased, albeit not significantly in both conditions (p > 0.05). In MS patients, percentage changes in MEP size induced by plasticity and metaplasticity protocol were significantly associated to EDSS (p = 0.001) and kinematics of index finger movements (p = 0.01).

Conclusion: M1 plasticity and metaplasticity are both altered in MS patients. When TBS is used for therapeutic purposes, TBS protocols should be tailored according to the M1 plasticity functional reserve of each MS patient.
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http://dx.doi.org/10.1016/j.msard.2019.101494DOI Listing
February 2020

Ten-Year Reflections on the Neurophysiological Abnormalities of Focal Dystonias in Humans.

Mov Disord 2019 11 8;34(11):1616-1628. Epub 2019 Oct 8.

Department of Human Neurosciences, Sapienza, University of Rome, Rome, Italy.

The physiological landscape of dystonia has changed considerably over the past 10 years. Initial ideas that dystonic motor symptoms could be explained by a combination of loss of inhibition and increased plasticity, together with subtle deficits in sensory processing, have been questioned, whereas the possible role of the cerebellum has risen in importance. In addition, it has been recognized that symptoms affect more than just the motor and sensory systems and encompass independent cognitive and psychological changes. Finally, it has become clear that, despite similarities in symptoms, there may be pathophysiological differences between idiopathic, inherited, and acquired forms of dystonia. In other words, progress in the pathophysiology of dystonia has followed the usual pattern from an initial phase in which core deficits are readily explained by highly simplified models to a realization that within a highly interconnected network, effects are more nuanced with widespread changes that might either compensate or contribute to the clinical symptoms to different degrees in different individuals. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27859DOI Listing
November 2019

Retrospectively acquired cohort study to evaluate the long-term impact of two different treatment strategies on disability outcomes in patients with relapsing multiple sclerosis (RE.LO.DI.MS): data from the Italian MS Register.

J Neurol 2019 Dec 18;266(12):3098-3107. Epub 2019 Sep 18.

Department of Basic Medical Sciences, Neurosciences, and Sense Organs, Multiple Sclerosis Center, University of Bari "Aldo Moro", Bari, Italy.

Background: The increase in disease-modifying drugs (DMDs) allows individualization of treatment in relapsing multiple sclerosis (RMS); however, the long-term impact of different treatment sequences is not well established. This is particularly relevant for MS patients who may need to postpone more aggressive DMD strategies.

Objective: To evaluate different therapeutic strategies and their long-term outcomes, measured as relapses and confirmed disability progression (CDP), in MS 'real-world' settings.

Methods: Multicentre, observational, retrospectively acquired cohort study evaluating the long-term impact of different treatment strategies on disability outcomes in patients with RMS in the Italian MS Register.

Results: We evaluated 1152 RMS-naïve patients after propensity-score adjustment. Patients included were receiving: interferon beta-1a (IFN-β1a) 44 µg switching to fingolimod (FTY; IFN-switchers; n = 97); FTY only (FTY-stayers; n = 157); IFN-β1a only (IFN-stayers; n = 849). CDP and relapses did not differ between FTY-stayers and IFN-switchers [HR (95% CI) 0.99 (0.48-2.04), p = 0.98 and 0.81 (0.42-1.58), p = 0.55, respectively]. However, IFN-stayers showed increased risk of relapses compared with FTY-stayers [HR (95% CI) 1.46 (1.00-2.12), p = 0.05].

Conclusion: The ideal treatment option for MS is becoming increasingly complex, with the need to balance benefit and risks. Our results suggest that starting with FTY affects the long-term disease outcome similarly to escalating from IFN-β1a to FTY.
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http://dx.doi.org/10.1007/s00415-019-09531-6DOI Listing
December 2019