Sebastiano ARCERI

@mondino.it

Neurology, Department of Nervous System and Behavioral Sciences
Fondazione Mondino, Istituto Neurologico Nazionale a carattere scientifico (IRCCS)

Sebastiano ARCERI


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15

Scopus Publications

Scopus Publications

  • Abnormal swallowing–breathing coordination is an electrokinesiographic feature of dysphagia in multiple system atrophy: a comparative study with Parkinson’s disease
    Massimiliano Todisco, Enrico Alfonsi, Sebastiano Arceri, Paolo Prunetti, Mauro Fresia, Roberta Zangaglia, Cristina Tassorelli, Antonio Pisani, Giuseppe Cosentino
    Journal of Neural Transmission, 2026
  • Increased Cerebrospinal Fluid Biomarkers of Neurodegeneration in Acquired Progressive Ataxia and Palatal Tremor Following a Static Lesion: A Case Report
    Carlo Fazio, Simone Regalbuto, Sebastiano Arceri, Davide Comolli, Alessandra Calculli, Piergiorgio Grillo, Giuseppe Cosentino, Liliana Brambilla, Daniela Rossi, Antonio Pisani
    Movement Disorders Clinical Practice, 2025
    Progressive ataxia and palatal tremor (PAPT) is a rare syndrome combining palatal tremor and progressive cerebellar ataxia. PAPT is classified into familial and sporadic forms, but etiopathogenesis remains largely unclear.1 Recent neuropathological and positron emission tomography studies2, 3 revealed tau deposition in brains of patients affected by sporadic PAPT, suggesting it may be a novel tauopathy. Another condition, termed “oculo-palatal tremor and tardive ataxia”4 has been described as a rare complication of large brainstem lesions with onset from months to years following a monophasic lesion.4, 5 It has been suggested that this syndrome could be considered as an acquired or structural form of PAPT (sPAPT).1 Although the progressive course of sPAPT suggests a neurodegenerative phenomenon,4, 5 to date no clear evidence in support of this hypothesis has been presented. A 70-year-old male presented with progressive gait ataxia, dysarthria, and oscillopsia over the past 3.5 years. Past medical history, included mild hypertension and atrial fibrillation treated with amiodarone. Four years before he experienced a spontaneous right pontine-midbrain hemorrhage treated with surgical drainage. Post-surgery, his neurological exam showed mild left pyramidal signs, vertical and horizontal gaze palsy, mild imbalance, and upper right limb ataxia. After rehabilitation, he reported full recovery of gait issues. However, 8 months later, he began to develop progressive imbalance, dysarthria, and oscillopsia. A magnetic resonance imaging (MRI) showed hemosiderin deposition in the right pontine-midbrain and T2-weighted hyperintensity in the inferior olives, indicating hypertrophic olivary degeneration (HOD), a hallmark of PAPT. A DaTscan ruled out presynaptic dopaminergic denervation. Two years later, he developed dyspnea and throat tingling. An otorhinolaryngologist observed rhythmic rest laryngeal spasms and referred the patient to our clinic. Neurological examination on admission revealed stable signs because of previous hemorrhage, including left sensory-motor deficit, upper right limb ataxia, vertical gaze supranuclear palsy, bilateral restriction in abduction of both eyes (more severe on left), and left hypotropia (Video 1). Additionally, he showed a progressive cerebellar syndrome with prominent trunk, gait, and speech ataxia. He also exhibited palato-laryngeal rhythmic activation consistent with palatal tremor and a synchronous pendular nystagmus in all directions of gaze, more evident in left eye (Video 2). MRI confirmed bilateral HOD and persistent hemosiderin deposit affecting midbrain, pons, and superior cerebellar peduncle, without significant cerebellar atrophy (Fig. 1). Electromyography (EMG) of laryngeal muscles showed a 2 Hz pseudo-rhythmic activation of thyroarytenoid and cricoarytenoid muscles, indicating larynx involvement (Fig. 2). A genetic screening for ataxia covering nearly 50 genes (next generation sequencing panel) ruled out pathogenic mutations associated with spinocerebellar ataxia (SCA) as well as familial PAPT forms (POLG, GFAP, and SPG7). SCA20 and neurodegeneration with brain iron accumulation 3 (NBIA3), instead, were considered improbable based on neuroimaging. Neuropsychological tests indicated mild deficits in frontal-executive functions. Cerebrospinal fluid (CSF) analysis (chemiluminescence enzyme immunoassay) revealed increased levels of total tau (t-tau) (844 pg/mL, normal values <404 pg/mL) and phosphorylated tau (p-tau) (113.60 pg/mL, normal values <56.5 pg/mL) proteins, whereas β-amyloid levels were normal. Neurofilament light chains (Nf-L) were also elevated (1.12 ng/mL) (NF-light ELISA CE). The patient was discharged with gabapentin 900 mg/daily. After 6 months, there was slight improvement in palatal tremor and oscillopsia, but speech impairment and ataxia remained unchanged. sPAPT is a rare condition characterized by distinct clinical and neuroimaging features. Our patient demonstrated typical signs, including progressive cerebellar ataxia and oculo-palatal tremor, which were supported by brain MRI findings and consistent EMG data. Our case provides novel EMG data on laryngeal involvement, which is rarely reported. Most notably, our patient showed elevated levels of CSF t-tau, p-tau, and Nf-L, indicating a potential neurodegenerative process. Other tauopathies such as Alzheimer's disease, chronic traumatic encephalopathy, progressive supranuclear palsy, and cortico-basal degeneration were deemed improbable based on clinical presentation and negative auxiliary tests. Moreover, it was unlikely that the elevation of CSF biomarkers was a residue of the neuronal damage occurred during the acute cerebrovascular event. CSF tau levels, indeed, usually rise within hours, peak at 5 to 7 days, and normalize after few months following stroke.6 To our knowledge, this is the first report of elevated neurodegeneration CSF biomarkers in sPAPT. These findings, associated with progressive clinical course and onset of symptoms after static lesion, support a degenerative process not only in sporadic cases of PAPT, but also in structural forms, hence differentiating sPAPT from other forms of acquired PAPT (ie, infectious or autoimmune). In our patient, temporal correlation with hemorrhagic stroke suggests a secondary rather than primary neurodegenerative phenomenon. As already suggested by other authors,5 persistent hemosiderin deposition, evident in our case, may play a crucial role, potentially triggering secondary neurodegeneration. Ferroptosis, a type of iron-dependent cell death, is being investigated as a potential mechanism in various neurodegenerative conditions.7 Iron can bind to tau, inducing its phosphorylation,8 and iron overload may lead to tau accumulation and hyperphosphorylation.9 In turn, tau and p-tau accumulation might further disrupt iron homeostasis, creating a vicious cycle that leads to neuronal degeneration.10 Although secondary neurodegeneration in our case remains speculative, we propose that persistent hemosiderin and elevated tau and p-tau levels in CSF could result from iron-tau interaction. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3)Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. C.F.: 1A, 3A S.R.: 1A, 3B S.A.: 1C, 3B D.C.: 3B A.C.: 3B P.G.: 3B G.C.: 3B L.B.: 1C D.R.: 1C, 3B AP: 1A, 1B, 3B We thank the patient, his family and the Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation Servizio di Medicina di Laboratorio (SMEL) laboratory for CSF analysis. Open access publishing facilitated by Universita degli Studi di Pavia, as part of the Wiley - CRUI-CARE agreement. Ethical Compliance Statement: The authors confirm that the approval of an institutional review board was not required for this work. Informed patient consent was regularly obtained for video usage. Both oral and written consent was obtained. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding sources and Conflict of Interest: The work is supported by NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery, and Resilience Plan (NRRP), project MNESYS (PE0000006) – A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022), and by Italian Ministry of Health “Ricerca Corrente 2022–2024” granted to IRCCS Mondino Foundation. The authors declare that there are no conflicts of interest relevant to this work. Funding Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report. The data that support the findings of this study are available from the corresponding author upon reasonable request.
  • Clinical correlates of obstructive sleep apnoea in idiopathic normal pressure hydrocephalus
    Simone Regalbuto, Roberta Zangaglia, Francesca Valentino, Massimiliano Todisco, Claudio Pacchetti, Matteo Cotta Ramusino, Federico Mazzacane, Marta Picascia, Sebastiano Arceri, Gaetano Malomo, Elena Capriglia, Laura Spelta, Annalisa Rubino, Antonio Pisani, Michele Terzaghi
    European Journal of Neurology, 2024
    Background and purposeThe pathogenesis of idiopathic normal pressure hydrocephalus (iNPH) remains controversial. Limited studies have indicated a high prevalence of obstructive sleep apnoea (OSA) amongst iNPH patients. The aim was to investigate the clinical correlates of OSA in iNPH patients.MethodsIn this cross‐sectional observational study, consecutive iNPH patients were prospectively enrolled. Evaluations included the iNPH Rating Scale, the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the time and number of steps to walk 10 m, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, a complete neuropsychological evaluation, 3‐T brain MRI, full‐night video‐polysomnography, tap test and cerebrospinal fluid (CSF) neurodegeneration biomarkers.ResultsFifty‐one patients were screened, of whom 38 met the inclusion criteria. Amongst the recruited patients, 19/38 (50%) exhibited OSA, with 12/19 (63.2%) presenting moderate to severe disorder. OSA+ iNPH patients required more time (p = 0.02) and more steps (p = 0.04) to complete the 10‐m walking test, had lower scores on the gait subitem of the iNPH Rating Scale (p = 0.04) and demonstrated poorer performance on specific neuropsychological tests (Rey Auditory Verbal Learning Test immediate recall, p = 0.03, and Rey–Osterrieth Complex Figure, p = 0.01). Additionally, OSA+ iNPH patients had higher levels of total tau (p = 0.02) and phospho‐tau (p = 0.03) in their CSF but no statistically significant differences in beta‐amyloid (1–42) levels compared to OSA− iNPH patients.ConclusionObstructive sleep apnoea is highly prevalent in iNPH patients, particularly at moderate to severe levels. OSA is associated with worse motor and cognitive performance in iNPH. The CSF neurodegeneration biomarker profile observed in OSA+ iNPH patients may reflect OSA‐induced impairment of cerebral fluid dynamics.
  • Pseudo-Orthostatic Tremor in Graves’ Disease: A Possible Early Sign of Parkinsonism?
    Davide Comolli, Simone Regalbuto, Sebastiano Arceri, Giuseppe Trifirò, Alessandra Calculli, Carlo Fazio, Piergiorgio Grillo, Massimiliano Todisco, Antonio Pisani
    Tremor and Other Hyperkinetic Movements, 2024
    Background: Pseudo-orthostatic tremor is a hyperkinetic movement disorder usually associated with other neurological comorbidities, mainly Parkinson’s disease. Case report: A 65-year-old male presented with unsteadiness and leg tremor while standing. Electrophysiological evaluation confirmed the presence of pseudo-orthostatic tremor. Blood test showed an undiagnosed Graves’ disease. A complete remission of tremor was achieved with methimazole. Dopamine transporter scintigraphy showed a mild reduction of the striatal binding, bilaterally. Discussion: Graves’ disease can be associated with pseudo-orthostatic tremor. Thyroid function should be assessed in patients complaining of unsteadiness. The causative role of hyperthyroidism in determining dopaminergic degeneration and uncovering subclinical parkinsonism warrants further investigations.
  • Expanding the phenotype of Brunner syndrome from childhood to adulthood: Description of the second pediatric patient and his mother
    Maria Letizia Minniti, Silvia Kalantari, Ludovica Pasca, Samantha Bruno, Sebastiano Arceri, Elisa Novello, Elisa Giorgio, Vittoria Rizzo, Renato Borgatti, Enza Maria Valente, Antonio Pisani, Simona Orcesi, Fabio Sirchia
    American Journal of Medical Genetics Part A, 2024
    Brunner syndrome is a recessive X‐linked disorder caused by pathogenic variants in the monoamine oxidase A gene (MAOA). It is characterized by distinctive aggressive behavior, mild intellectual disability, sleep disturbances, and typical biochemical alterations deriving from the impaired monoamine metabolism. We herein describe a 5‐year‐old boy with developmental delay, autistic features, and myoclonic epilepsy, and his mother, who had mild intellectual disability and recurrent episodes of palpitations, headache, abdominal pain, and abdominal bloating. Whole exome sequencing allowed detection of the maternally‐inherited variant c.410A&gt;G, (p.Glu137Gly) in the MAOA gene. The subsequent biochemical studies confirmed the MAOA deficiency both in the child and his mother. Given the serotonergic symptoms associated with high serotonin levels found in the mother, treatment with a serotonin reuptake inhibitor and dietary modifications were carried out, resulting in regression of the biochemical abnormalities and partial reduction of symptoms. Our report expands the phenotypic spectrum of Brunner disease, bringing new perspectives on the behavioral and neurodevelopmental phenotype from childhood to adulthood.
  • Parkinson disease following COVID-19: Report of six cases
    Alessandra Calculli, Tommaso Bocci, Mattia Porcino, Micol Avenali, Chiara Casellato, Sebastiano Arceri, Simone Regalbuto, Alberto Priori, Antonio Pisani
    European Journal of Neurology, 2023
    BACKGROUND Core clinical manifestation of COVID-19 include flu-like and respiratory symptoms. However, it is now evident that neurological involvement may occur during SARS-CoV-2 infection, covering an extensive spectrum of phenotypical manifestations. A major challenge arising from this pandemic is represented by detecting emerging neurological complications following recovery from SARS-CoV-2 infection. To date, few post-COVID-19 infected subjects diagnosed with Parkinson's Disease (PD) were described, raising the possibility of a connection between the infection and neurodegenerative process. Here, we describe a cases series of six subjects, who developed PD after COVID-19. METHODS Patients were observed at IRCCS Mondino Foundation Hospital, Pavia (Italy), and San Paolo University Hospital of Milan (Italy) between March 2021 and June 2022. In all subjects, SARS-CoV-2 infection was confirmed by means of a RT-PCR from a nasopharyngeal swab. Subjects underwent an accurate neurological evaluation, and neuroimaging studies were performed. RESULTS We describe six subjects, who developed PD with an average time window after SARS-CoV-2 infection of 4-7 weeks. Apparently, no relationship with COVID-19 severity emerged, and no overt structural brain abnormalities were found. All subjects experienced unilateral resting tremor at onset and showed a satisfactory response to dopaminergic treatment. CONCLUSIONS Immune responses to SARS-CoV-2 infection have been shown to shape the individual susceptibility to develop long-term consequences. We hypothesize that, in these subjects, COVID-19 has unmasked a latent neurodegenerative process. Characterization of the neuroinflammatory signatures in larger cohorts is warranted, which might provide novel insights in the pathogenesis of PD.
  • Chorea Associated with JAK2V617F-Positive Essential Thrombocythemia
    Alessandra Calculli, Sebastiano Arceri, Antonio Pisani
    Movement Disorders Clinical Practice, 2023
    It is with great interest that we read the article by Kutty and colleagues1 on chorea in patients with JAK2V617F-mutated essential thrombocythemia (ET). As pointed out by the authors, the occurrence of chorea has rarely been reported, and its pathogenesis remains controversial. We would like to add to this discussion by describing a 61-year-old woman with a 3-month history of slowly progressive chorea involving oromandibular district, left upper limb, and ipsilateral foot and toes. Five years before, the patient was diagnosed with JAK2V617F-mutation ET and treated with hydroxyurea (500 mg once-daily, OD). The subject autonomously interrupted the treatment right before symptoms onset. There was no history of other medical conditions or exposure to neuroleptic medication and no familiarity for neurological diseases. At admission to our department, her blood cell count showed platelet 816 × 10^3/μL, and brain magnetic resonance imaging (MRI) revealed no evidence of acute lesions but it did show a chronic vascular infarction in the right caudate nucleus. An autoantibodies panel, including ENA, ANA, ANCA, anti-gliadin, anti-cardiolipin, anti-beta-2-glycoprotein and LAC, was negative. An electroencephalogram detected non-specific slow-wave activity, and genetic testing for Huntington's disease was negative. During hospitalization, hydroxyurea was reintroduced at 1000 mg OD and tetrabenazine (12.5 mg twice-daily, TD) was started, observing substantial clinical improvement. At the 6-month follow-up, her neurological examination was normal, and the platelet count normalized. Three months later, tetrabenazine was gradually withdrawn. However, after 4 to 5 weeks, choreic movements reappeared in the same districts, triggered by walking. Tetrabenazine treatment was then reintroduced, with beneficial effects. Our case shares some similarities with the one described.1 In both cases, choreic movements coincided with deterioration of hematological parameters, which in our case was determined by voluntary withdrawal of hydroxyurea. Although we found a chronic ischemic lesion in the MRI, in a chorea of purely vascular nature, we would have expected a more acute presentation as well as a gradual resolution of symptoms, whereas similarly to the case reported,1 we also observed a slow, subacute onset of chorea, and, conversely, its gradual progression. Additionally, in our case, tetrabenazine interruption was followed shortly by symptom re-emergence. As proposed by the Koya Kutty et al.,1 blood hyperviscosity may not be sufficient to justify the development of chorea. In line with this view are the unusual symptom presentations and progression. An altered metabolic turnover of dopamine in the basal ganglia might cause adaptive changes in local transmitter content.1, 2 This hypothesis would fit with the prompt response to tetrabenazine. Recently, a role for JAK2 in neuroinflammation has been proposed. JAK2 is member of a family of tyrosine kinases coupled to multiple signaling pathways. In particular, JAK2-STAT3 pathway is required for astrocyte reactivity, and its inhibition reduces the astroglial response to quinolinic-acid-induced striatal lesions supporting its neuroprotective role,3, 4 which is expressed in striatal neurons. The JAK2−V617F mutation causes the loss of its auto-inhibitory activity, resulting in astrogliosis and inflammation. We postulate that local persistence of proinflammatory cytokines could impair striatal GABAergic signaling, generating choreic manifestations.5 Overall, it seems plausible that more than multiple pathophysiological factors concur in causing the appearance of chorea in these patients. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Data Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. A.C.: 1C, 3A. S.A.: 1B, 2B. A.P.: 1A, 2A, 2C, 3B. No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. The authors declare that there are no conflicts of interest relevant to this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Informed patient consent was verbally obtained. The authors confirm that the approval of an institutional review board was not required for this work. Open Access Funding provided by Universita degli Studi di Pavia within the CRUI-CARE Agreement.
  • BoNT-A efficacy in high frequency migraine: an open label, single arm, exploratory study applying the PREEMPT paradigm
    Daniele Martinelli, Sebastiano Arceri, Roberto De Icco, Marta Allena, Elena Guaschino, Natascia Ghiotto, Vito Bitetto, Gloria Castellazzi, Giuseppe Cosentino, Grazia Sances, Cristina Tassorelli
    Cephalalgia, 2022
    Introduction In this open label, single-arm trial we evaluated the efficacy of onabotulinum toxin-A in the prevention of high-frequency episodic migraine (8–14 migraine days/month). Methods We enrolled 32 high-frequency episodic migraine subjects (age 44.8 ± 11.9 years, 11.0 ± 2.2 migraine days, 11.5 ± 2.1 headache days, 7 females). After a 28-day baseline period, subjects underwent 4 subsequent onabotulinum toxin-A treatments according to the phase III research evaluating migraine prophylaxis therapy (PREEMPT) paradigm, 12-weeks apart. The primary outcome was the reduction of monthly migraine days from baseline in the 12-week period following the last onabotulinum toxin-A treatment Results Onabotulinum toxin-A reduced monthly migraine days by 3.68 days (−33.1%, p &lt; 0.01). Thirty-nine percent of the patients experienced a ≥50% reduction in monthly migraine days. Onabotulinum toxin-A also reduced the number of headache days (−33.9%, p &lt; 0.01) and the intake of acute medications (−22.9%, p = 0.03). Disability and quality of life (QoL) scores improved markedly (migraine disability assessment (MIDAS) −41.7%; migraine specific questionnaire (MSQ) −31.7%, p &lt; 0.01). Conclusions The findings suggest that, when administered according to the PREEMPT paradigm, onabotulinum toxin-A is effective in the prevention of high-frequency episodic migraine. Trial Registration: NCT04578782
  • Polymorphism in exercise genes and respiratory function in late-onset Pompe disease
    Sabrina Ravaglia, Alberto Malovini, Serena Cirio, Cesare Danesino, Paola De Filippi, Maurizio Moggio, Tiziana Mongini, Lorenzo Maggi, Serena Servidei, Andrea Vianello, Antonio Toscano, Paola Tonin, Maria Antonietta Maioli, Rossella Parini, Massimiliano Filosto, Grazia Crescimanno, Sebastiano Arceri, Manuela Piran, Annalisa Carlucci
    Journal of Applied Physiology, 2021
    Previous reports evaluated the role of exercise genes in influencing skeletal muscle phenotype and response to ERT in LOPD. Here, we investigate the role of polymorphisms in several exercise gene, focusing on respiratory muscles. ACE-DD and ACTN3-XX polymorphisms, possibly influencing muscle properties and fiber composition, were associated with more severe respiratory phenotypes.
  • COVID-19 in patients with myasthenia gravis: Epidemiology and disease course
    Pietro Businaro, Gloria Vaghi, Enrico Marchioni, Luca Diamanti, Sebastiano Arceri, Paola Bini, Elena Colombo, Giuseppe Cosentino, Enrico Alfonsi, Alfredo Costa, Sabrina Ravaglia, Giulia Mallucci, Elena Ballante, Diego Franciotta, Matteo Gastaldi
    Muscle and Nerve, 2021
    Coronavirus disease 2019 (COVID‐19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, has become a global pandemic. Patients with myasthenia gravis (MG), often treated with immunosuppressants, might be at higher risk of developing COVID‐19 and of demonstrating a severe disease course. We aimed to study prevalence and describe features of COVID‐19 in MG patients.
  • Buprenorphine may be effective for treatment of paramyotonia congenita
    Sabrina Ravaglia, Lorenzo Maggi, Antonio Zito, Sebastiano Arceri, Pietro Gallotti, Concetta Altamura, Jean Francois Desaphy, Pia Bernasconi, Enrico Alfonsi
    Muscle and Nerve, 2021
  • Isolated bulbar palsy after SARS-CoV-2 infection
    Massimiliano Todisco, Enrico Alfonsi, Sebastiano Arceri, Giulia Bertino, Carlo Robotti, Michele Albergati, Matteo Gastaldi, Cristina Tassorelli, Giuseppe Cosentino
    Lancet Neurology, 2021
  • KCTD17-related myoclonus-dystonia syndrome: clinical and electrophysiological findings of a patient with atypical late onset
    Massimiliano Todisco, Simone Gana, Giuseppe Cosentino, Edoardo Errichiello, Sebastiano Arceri, Micol Avenali, Enza Maria Valente, Enrico Alfonsi
    Parkinsonism and Related Disorders, 2020
  • Pitfals in recognition and management of trigeminal neuralgia
    F. Antonaci, S. Arceri, M. Rakusa, D. D. Mitsikostas, I. Milanov, V. Todorov, M. Cotta Ramusino, A. Costa, and
    Journal of Headache and Pain, 2020
  • Chronic migraine and Botulinum Toxin Type A: Where do paths cross?
    Daniele Martinelli, Sebastiano Arceri, Livio Tronconi, Cristina Tassorelli
    Toxicon, 2020