63 results on '"Maria Pia Giannoccaro"'
Search Results
2. Neural Surface Antibodies and Neurodegeneration: Clinical Commonalities and Pathophysiological Relationships
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Maria Pia Giannoccaro, Federico Verde, Luana Morelli, Giovanni Rizzo, Fortuna Ricciardiello, and Rocco Liguori
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Medicine (miscellaneous) ,General Biochemistry, Genetics and Molecular Biology - Abstract
Autoimmune encephalitis and neurodegenerative disorders share several clinical features, including behavioural and psychiatric manifestations, cognitive impairment, sleep and movement disorders. Therefore, it is not surprising that autoimmune encephalitis is one of the main differential diagnoses of rapidly progressive dementia. However, more chronic presentations of autoimmune disorders have been reported and can lead to the misdiagnosis of a neurodegenerative disease. On the other hand, antibodies against neuronal proteins, such as those directed against NMDAR, can occur during established neurogenerative disorders, and their role in this context is still unclear. They might be simple bystanders or modify the disease course and phenotype. Indeed, autoimmune encephalitis can leave long-term cognitive sequelae and specific antibodies to neuronal surface antigens are associated with clinical and pathological neurodegenerative features. Here we review the link between these antibodies and neurodegeneration. In particular we discuss: (a) the possibility that autoimmune encephalitis presents as a neurodegenerative disease, identifying the red flags that can help in the differential diagnosis between antibody-mediated and neurodegenerative disorders; (b) the occurrence of antibodies against neuronal surface antigens in patients with neurodegenerative disorders and their possible role in the disease course; and (c) the long-term cognitive and neuroradiological changes associated with autoimmune encephalitis, as well as the biomarkers that can help to predict the cognitive outcome. Finally, we review the clinical and pathological features of IgLON5 antibodies-related encephalitis, a unique model of the relationship between antibodies and neurodegeneration.
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- 2023
3. GABAA receptor and anti-titin antibody encephalitis in a patient with thymoma
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Maria Tappatà, Maria Pia Giannoccaro, Michele Romoli, Stefania Testoni, Giorgia Arnone, Laura Piccolo, Piergiorgio Solli, Anna Zaniboni, Federica Naldi, Keivan Kaveh Moghadam, Nazarena Nannini, Stefania Damiani, Rocco Liguori, and Andrea Zini
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Male ,Psychiatry and Mental health ,Thymoma ,Encephalitis ,Humans ,Neurology (clinical) ,Dermatology ,General Medicine ,Hashimoto Disease ,Thymus Neoplasms ,Receptors, GABA-A ,Aged ,Autoantibodies - Abstract
Autoimmune encephalitis (AE) associated to antibodies against GABA A R is a rare form of encephalitis. On the other hand, thymoma has been linked to antibodies against both muscular and neuronal epitopes, even if concurrent positivity for more than one antibody is exceptional, and their contribution to the clinical course and treatment decision is unclear. We report a case of a 73-year-old male with AE associated with thymoma secreting both anti-GABAaR and anti-titin antibodies. Clinical presentation included status epilepticus, behavioural changes and cognitive decline. While the status was stopped with lacosamide, AE treatment included first- and second-line immunomodulation, in addition to thymoma's removal. Nonetheless, the patient experienced a worsening in cognitive and behavioural status.
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- 2022
4. Multiple sclerosis in patients with hereditary spastic paraplegia: a case report and systematic review
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Maria Pia Giannoccaro, Eleonora Matteo, Fiorina Bartiromo, Caterina Tonon, Filippo M. Santorelli, Rocco Liguori, and Giovanni Rizzo
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Adult ,Psychiatry and Mental health ,Multiple Sclerosis ,Spastic Paraplegia, Hereditary ,Oligoclonal Bands ,Humans ,Female ,Neurology (clinical) ,Dermatology ,General Medicine ,Retrospective Studies - Abstract
An increasing number of cases of comorbid hereditary spastic paraplegia (HSP) and multiple sclerosis (MS) have been described. We report a patient with the SPG3A form of HSP and features of relapsing-remitting MS (RRMS). We took this opportunity to review the current literature of co-occurring MS and HSP.The patient underwent clinical, laboratory and neuroimaging evaluations. We performed a literature search for cases of HSP and MS. The 2017 McDonalds Criteria for MS were retrospectively applied to the selected cases.A 34-year-old woman, presenting a molecular diagnosis of SPG3A, complained subacute sensory-motor symptoms. Spinal MRI disclosed T2-hyperintense lesions at C2, T6 and T4 level, the latter presenting contrast-enhancement. CSF analysis showed oligoclonal bands. She was treated with intravenous high-dose steroids, with symptom resolution. The literature review yielded 13 papers reporting 20 possible cases of MS and HSP. Nine patients (5 M, median age 34) met the 2017 McDonald criteria. Five (25%) received a diagnosis of RRMS and four (20%) of primary progressive MS. Brain MRI showed multiple WM lesions, mostly periventricular. Six of seven cases (85.7%) had spinal cord involvement. Oligoclonal bands were found in 6/8 (75%) patients. Seven patients (77.7%) improved/stabilized on immunotherapy.This is the first description on the association between SPG3A type of HSP and MS. This report adds to the other reported cases of co-occurring HSPs and MS. Although it remains unclear if this association is casual or causal, clinicians should be aware that an HSP diagnosis does not always exclude a concomitant MS.
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- 2022
5. Difference in safety and humoral response to mRNA SARS-CoV-2 vaccines in patients with autoimmune neurological disorders: the ANCOVAX study
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Maria Pia, Giannoccaro, Veria, Vacchiano, Marta, Leone, Federico, Camilli, Corrado, Zenesini, Ivan, Panzera, Alice, Balboni, Maria, Tappatà, Annamaria, Borghi, Fabrizio, Salvi, Alessandra, Lugaresi, Rita, Rinaldi, Giulia, Di Felice, Vittorio, Lodi, Tiziana, Lazzarotto, Rocco, Liguori, and Roberto, Michelucci
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Adult ,COVID-19 Vaccines ,Fingolimod Hydrochloride ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,Antibodies, Viral ,Immunity, Humoral ,Autoimmune Diseases of the Nervous System ,Immunoglobulin G ,Humans ,Longitudinal Studies ,BNT162 Vaccine ,2019-nCoV Vaccine mRNA-1273 ,Aged - Abstract
Assessing the safety of SARS-CoV-2 mRNA vaccines and the effect of immunotherapies on the seroconversion rate in patients with autoimmune neurological conditions (ANC) is relevant to clinical practice. Our aim was to assess the antibody response to and safety of SARS-CoV-2 mRNA vaccines in ANC.This longitudinal study included ANC patients vaccinated with two doses of BNT162b2 or mRNA-1273 between March and August 2021. Side effects were assessed 2-10 days after each dose. Neurological status and anti-spike receptor binding domain antibody levels were evaluated before vaccination and 4 weeks after the second dose. Healthcare-workers served as controls for antibody levels.We included 300 ANC patients (median age 52, IQR 40-65), and 347 healthcare-workers (median age 45, IQR 34-54). mRNA-1273 vaccine was associated with an increased risk of both local (OR 2.52 95% CI 1.45-4.39, p = 0.001) and systemic reactions (OR 2.51% CI 1.49-4.23, p = 0.001). The incidence of relapse was not different before and after vaccine (Incidence rate ratio 0.72, 95% CI 0.29-1.83). Anti-SARS-CoV-2 IgG were detected in 268 (89.9%) patients and in all controls (p 0.0001). BNT162b2 vaccine (OR 8.84 95% CI 2.32-33.65, p = 0.001), anti-CD20 mAb (OR 0.004 95% CI 0.0007-0.026, p 0.0001) and fingolimod (OR 0.036 95% CI 0.002-0.628, p = 0·023) were associated with an increased risk of not developing anti-SARS-CoV-2 IgG.SARS-CoV-2 mRNA vaccines were safe in a large group of ANC patients. Anti-CD20 and fingolimod treatment, as well as vaccination with the BNT162b2 vaccine, led to a reduced humoral response. These findings could inform vaccine policies in ANC patients undergoing immunotherapy.
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- 2022
6. Pilomotor seizures in autoimmune limbic encephalitis: description of two GAD65 antibodies- related cases and literature review
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Federica Pondrelli, Maria Pia Giannoccaro, Francesca Bisulli, Lorenzo Ferri, Veronica Menghi, Barbara Mostacci, Patrizia Avoni, Rocco Liguori, Paolo Tinuper, and Laura Licchetta
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Neurology ,Limbic Encephalitis ,Humans ,Electroencephalography ,Neurology (clinical) ,General Medicine ,Autoantibodies ,Autoimmune Diseases - Abstract
Ictal piloerection (IP) is a rare manifestation of focal epilepsy. Autoimmune limbic encephalitis (LE) and malignant brain tumours are the most frequent recognized aetiologies.We selected all patients diagnosed with LE in our Institute from 2004 to 2020 and manifesting with IP. We performed a literature review on LE patients presenting IP.Of 15 patients diagnosed with LE (13.3%), two manifested IP as prominent ictal feature. One of them also had stiff-limb syndrome. Video-EEG documented ictal discharges from the right temporal regions with concomitant sympathetic skin response (SSR) recording. Antibody testing showed elevated serum and CSF titres of GAD65 antibodies (Ab), in both cases. Despite a combination of several anti-seizure medications and first- and second-line immunotherapy, they showed a poor clinical outcome after 2 and 9 years of follow-up, respectively. The literature review yielded 13 papers reporting 26 LE cases with IP. LGI1 Ab were the most frequently associated (73.1%) followed by VGKC-complex (7.7%), GAD65 (7.7%), NMDAr (3.8%), Ma2 (3.8%) and Hu (3.8%) Ab. Cases with LGI1 Ab showed a good response to immunotherapy.The prevalence of IP in our LE cohort was of 13.3%, higher than expected. According to the literature review, most cases were associated with LGI1 Ab and showed a good response to immunotherapy. With the contribution of our cases, GAD65 emerged as the second most frequently detected Ab, showing a poor outcome. Our findings widen the spectrum of IP-associated Ab, with the respective prognostic implications.
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- 2022
7. Comparison of ice pack test and single-fiber EMG diagnostic accuracy in patients referred for myasthenic ptosis
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Corrado Zenesini, Rocco Liguori, Vincenzo Donadio, Matteo Paolucci, Maria Pia Giannoccaro, Vitantonio Di Stasi, Patrizia Avoni, Giannoccaro M.P., Paolucci M., Zenesini C., Di Stasi V., Donadio V., Avoni P., and Liguori R.
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IPT ,medicine.medical_specialty ,Ocular myasthenia ,Single fiber emg ,ice pack test ,ocular myasthenia ,Diagnostic accuracy ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Ptosis ,Internal medicine ,parasitic diseases ,0502 economics and business ,medicine ,In patient ,Receiver operating characteristic ,business.industry ,05 social sciences ,medicine.disease ,Predictive value ,Confidence interval ,single fiber EMG ,050211 marketing ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveTo compare the diagnostic accuracy of ice pack test (IPT) and single-fiber EMG (SF-EMG) in patients with suspected ocular myasthenia (OM) presenting with ptosis.MethodsWe studied consecutive patients referred for the clinical suspicion of OM. Patients underwent IPT and stimulated SF-EMG on the orbicularis oculi muscle. Receiver operating characteristic curve analysis was performed to determine the accuracy of IPT, SF-EMG, and their combination.ResultsWe included 155 patients, 102 with OM and 53 with other diagnosis (OD). The IPT had a sensitivity of 86% (95% confidence interval [CI] 79–93) and a specificity of 79% (95% CI 68–90). SF-EMG showed a sensitivity of 94% (95% CI 89–98) and a specificity of 79% (95% CI 68–90). Overall, IPT and SF-EMG showed discordant results in 30 cases, 16 OM and 14 OD. The combination of IPT and SF-EMG, using the positivity of at least one test for OM diagnosis, increased the sensitivity to 98% (95% CI 95–100), reducing the specificity to 66% (95% CI 53–78), whereas using the positivity of both tests, we obtained a sensitivity of 82% (95% CI 75–90) and a specificity of 92% (95% CI 85–99). The negativity of both tests had a 94% (95% CI 87–100) negative predictive value. Comparison of the areas under the curve showed no differences in the diagnostic accuracy of IPT, SF-EMG, and their combinations.ConclusionsIPT and SF-EMG have similar diagnostic accuracy in patients with OM presenting with ptosis. The negativity of both tests strongly suggests another diagnosis.Classification of evidenceThis study provides Class I evidence that both the IPT and SF-EMG accurately identify patients with OM.
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- 2020
8. Presence of Skin α-Synuclein Deposits Discriminates Parkinson's Disease from Progressive Supranuclear Palsy and Corticobasal Syndrome
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Maria Pia Giannoccaro, Patrizia Avoni, Giovanni Rizzo, Alex Incensi, Rossella Infante, Vincenzo Donadio, Rocco Liguori, Giannoccaro, Maria Pia, Avoni, Patrizia, Rizzo, Giovanni, Incensi, Alex, Infante, Rossella, Donadio, Vincenzo, and Liguori, Rocco
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organic chemicals ,Parkinson Disease ,corticobasal syndrome ,progressive supranuclear paly ,nervous system diseases ,Cellular and Molecular Neuroscience ,Corticobasal Degeneration ,Parkinsonian Disorders ,Parkinson’s disease ,alpha-Synuclein ,biomarker ,Humans ,Neurology (clinical) ,Supranuclear Palsy, Progressive ,skin biopsy ,parkinsonism - Abstract
Background: Previous studies reported skin phosphorylated α-synuclein (p-syn) deposits in Parkinson’s disease (PD) patients but not in patients with parkinsonism due to tauopathies, although data on the latter are limited. Objective: We aimed to assess the presence of skin p-syn deposits in patients with clinical diagnosis of parkinsonism usually due to tauopathy and PD. Methods: We consecutively recruited 26 patients, 18 fulfilling clinical diagnostic criteria of progressive supranuclear palsy (PSP) and 8 of corticobasal syndrome (CBS), 26 patients with PD, and 26 healthy controls (HC). All subjects underwent skin biopsy to study p-syn deposits in skin nerves by immunofluorescence. Results: Skin p-syn deposits were present in only two of the PSP/CBS patients and none of the HC. Conversely, all PD patients showed p-syn deposition (p
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- 2021
9. Antibody-mediated central nervous system diseases
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Angela Vincent, Sarah Crisp, Maria Pia Giannoccaro, Giannoccaro MP, Crisp SJ, Vincent A., Crisp, Sarah [0000-0002-0007-7775], and Apollo - University of Cambridge Repository
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0301 basic medicine ,CASPR2 ,Central nervous system ,Review Article ,03 medical and health sciences ,0302 clinical medicine ,Autoantibody ,Neurotransmitter receptor ,Glioma ,Medicine ,Glycine receptor ,Autoimmune encephalitis ,biology ,Clinical neuroscience ,neurodevelopment ,business.industry ,General Neuroscience ,medicine.disease ,NMDA receptor ,autoimmune encephalitis ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,LGI1 ,Neurology (clinical) ,Antibody ,business ,Neuroscience ,Autoantibody, autoimmune encephalitis, neurodevelopment, NMDA receptor, LGI1, CASPR2 ,030217 neurology & neurosurgery - Abstract
Antibody-mediated central nervous system diseases are a relatively new area of clinical neuroscience with growing impact. Their recognition has challenged the dogma of the blood–brain barrier preventing antibody access into the central nervous system. The antibodies discovered so far are mainly against neurotransmitter receptors (e.g. N-methyl-d-aspartate and glycine receptors) and ion channel–associated proteins (leucine-rich glioma inactivated protein 1 and contactin-associated protein 2) and are expressed on the surface of neuronal synapses and elsewhere. The disorders are reversible with immunotherapies that reduce antibody levels. Although rare, the identification of these disorders in clinical practice has made central nervous system autoimmune diseases a consideration in the differential diagnoses of many clinical presentations. There is still much to learn about the aetiology of the diseases and the mechanisms by which the antibodies act, the neuronal and glial changes that follow antibody-attack, and the compensatory changes that may be required to ensure good recovery.
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- 2021
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10. In vivo Mechanisms of Antibody-Mediated Neurological Disorders: Animal Models and Potential Implications
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Maria Pia Giannoccaro, Sukhvir K. Wright, Angela Vincent, and Maria Pia Giannoccaro, Sukhvir K. Wright, Angela Vincent
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0301 basic medicine ,Offspring ,Disease ,Review ,Active immunization ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,neuronal surface antibodies ,medicine ,maternal transfer ,animal models, neuronal surface antibodies, passive transfer, maternal transfer, active immunization ,Receptor ,lcsh:Neurology. Diseases of the nervous system ,Autoimmune encephalitis ,passive transfer ,biology ,business.industry ,medicine.disease ,active immunization ,animal models ,3. Good health ,030104 developmental biology ,Neurology ,biology.protein ,Neurology (clinical) ,Antibody ,business ,Neuroscience ,030217 neurology & neurosurgery ,Encephalitis - Abstract
Over the last two decades, the discovery of antibodies directed against neuronal surface antigens (NSA-Abs) in patients with different forms of encephalitis has provided a basis for immunotherapies in previously undefined disorders. Nevertheless, despite the circumstantial clinical evidence of the pathogenic role of these antibodies in classical autoimmune encephalitis, specific criteria need to be applied in order to establish the autoimmune nature of a disease. A growing number of studies have begun to provide proof of the pathogenicity of NSA-Abs and insights into their pathogenic mechanisms through passive transfer or, more rarely, through active immunization animal models. Moreover, the increasing evidence that NSA-Abs in the maternal circulation can reach the fetal brain parenchyma during gestation, causing long-term effects, has led to models of antibody-induced neurodevelopmental disorders. This review summarizes different methodological approaches and the results of the animal models of N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein 2 (CASPR2), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antibody-mediated disorders and discuss the results and the limitations. We also summarize recent experiments that demonstrate that maternal antibodies to NMDAR and CASPR2 can alter development in the offspring with potential lifelong susceptibility to neurological or psychiatric disorders.
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- 2020
11. Movement Disorders Associated with <scp> GABA A </scp> Receptor Encephalitis: A Video Case Report
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Veria Vacchiano, Maria Pia Giannoccaro, Rocco Liguori, Rita Rinaldi, Maria Guarino, Vacchiano V., Giannoccaro M.P., Rinaldi R., Guarino M., and Liguori R.
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Autoimmune encephalitis ,Movement disorders ,business.industry ,GABAA receptor ,Case Reports ,medicine.disease ,GABA ,Neurology ,Immunology ,R antibodie ,movement disorders ,Medicine ,Neurology (clinical) ,autoimmune encephaliti ,medicine.symptom ,business ,Encephalitis - Abstract
n.a.
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- 2020
12. Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome
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Judith Cossins, Øystein Fluge, Kari Sørland, Maria Pia Giannoccaro, Angela Vincent, Giannoccaro, Maria Pia, Cossins, Judith, Sørland, Kari, Fluge, Øystein, and Vincent, Angela
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Adult ,Male ,LRP4 ,Encephalopathy ,02 engineering and technology ,Disease ,030204 cardiovascular system & hematology ,chronic fatigue syndrome ,Antibodies ,Young Adult ,03 medical and health sciences ,020210 optoelectronics & photonics ,0302 clinical medicine ,Immune system ,0202 electrical engineering, electronic engineering, information engineering ,Chronic fatigue syndrome ,medicine ,Humans ,Pharmacology (medical) ,Aged ,Pharmacology ,Fatigue Syndrome, Chronic ,biology ,business.industry ,Autoantibody ,Radioimmunoassay ,myalgic encephalopathy ,Middle Aged ,NMDA receptor ,medicine.disease ,Neuroimmunology ,antibodie ,Case-Control Studies ,neuronal surface antigens ,Immunology ,biology.protein ,Female ,Antibody ,business - Abstract
Purpose A role for the immune system in causing myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is long suspected, but few studies have looked for specific autoantibodies that might contribute to the symptoms. Our aim was to look for evidence of antibodies to neuronal proteins in patients with ME/CSF. Methods Sera samples from 50 patients and 50 healthy individuals were sent coded to the Neuroimmunology Laboratory in Oxford. Screening for antibody binding to neuronal tissue was performed on brain tissue and neuronal cultures. Specific serum antibodies were assessed by antigen-specific cell-based assays and radioimmunoassays. After antibody testing, the associations between seropositive status and clinical data were investigated. Findings Overall, 8 patients and 11 participants were found to have some serum immunoreactivity toward neuronal or neuromuscular junction proteins, but only 1 patient and 2 participants had specific serum antibodies. Nevertheless, seropositive status in patients with ME was associated with shorter duration since onset and a more severe disease. Implications The results indicate no overall increased frequency of antibodies to neuronal proteins in ME/CSF and no evidence of a specific antibody that might be causative or contribute to clinical features in patients. However, the association of seropositive status with shorter duration of disease and more severe symptoms suggests a possible role of antibodies at onset in some patients and should be the focus of future studies.
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- 2019
13. Prognostic value of EMG genioglossus involvement in amyotrophic lateral sclerosis
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Sabina Capellari, Ilaria Bartolomei, Vitantonio Di Stasi, Giovanni Rizzo, Patrizia Avoni, Fabrizio Salvi, Rocco Liguori, Vincenzo Donadio, Maria Pia Giannoccaro, Veria Vacchiano, Vacchiano V., Di Stasi V., Rizzo G., Giannoccaro M.P., Donadio V., Bartolomei I., Capellari S., Salvi F., Avoni P., and Liguori R.
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Male ,medicine.medical_specialty ,Prognosi ,Genioglossu ,Facial Muscles ,Motor Neuron ,Lower motor neuron ,Masseter muscle ,Masseter ,Dysarthria ,EMG ,stomatognathic system ,Tongue ,Retrospective Studie ,Physiology (medical) ,Statistical significance ,Internal medicine ,medicine ,Humans ,Amyotrophic lateral sclerosis ,Retrospective Studies ,Aged ,Motor Neurons ,Genioglossus ,business.industry ,Upper motor neuron ,Electromyography ,Amyotrophic Lateral Sclerosis ,Middle Aged ,Prognosis ,medicine.disease ,Dysphagia ,Sensory Systems ,Facial Muscle ,body regions ,medicine.anatomical_structure ,Neurology ,Cardiology ,Female ,Neurology (clinical) ,medicine.symptom ,ALS ,business ,Amyotrophic Lateral Sclerosi ,Human - Abstract
Objective To evaluate the prognostic value of needle electromyography (EMG) genioglossus involvement in patients with amyotrophic lateral sclerosis (ALS) at diagnosis. Methods We separately explored the prognostic value of clinical bulbar lower motor neuron (LMN) signs and EMG genioglossus involvement using Cox proportional hazard models adjusted for age, gender, diagnostic delay, presence of bulbar upper motor neuron (UMN) signs, EMG cervical and lumbosacral region involvement, ALSFRS-R score and C9Orf72 gene status. Then, we compared the prognostic value of EMG masseter and genioglossus abnormalities in a subset of patients in whom both muscles were analysed. Results 103 ALS patients were included in the study. Neurophysiological genioglossus involvement was associated with a shorter survival (p = 0.002), a shorter time to moderate dysphagia (p = 0.0001) and to severe dysarthria (p = 0.012). Its prognostic value was still evident in patients without clinical bulbar LMN signs. Bulbar clinical LMN signs were only associated with an earlier onset of moderate dysphagia (p = 0.0001). EMG masseter abnormalities did not reach statistical significance with regard to all the clinical milestones. Conclusions Genioglossus EMG at diagnosis could provide important information about ALS progression rate. The masseter muscle seems to be less involved in ALS. Significance EMG genioglossus involvement is a prognostic factor in ALS.
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- 2021
14. Presynaptic paraneoplastic disorders of the neuromuscular junction: An update
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Maria Pia Giannoccaro, Rocco Liguori, Patrizia Avoni, Giannoccaro M.P., Avoni P., and Liguori R.
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Presynaptic disorders ,CASPR2 ,Neuromyotonia ,Neuromuscular transmission ,Neuromuscular junction ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Review ,Immune checkpoint inhibitor ,immune checkpoint inhibitors ,Postsynaptic potential ,Lambert Eaton myasthenic syndrome ,Medicine ,Voltage-dependent calcium channel ,business.industry ,General Neuroscience ,medicine.disease ,Myasthenia gravis ,medicine.anatomical_structure ,Paraneoplastic syndrome ,business ,Lambert-Eaton myasthenic syndrome ,Neuroscience ,Acetylcholine ,RC321-571 ,medicine.drug - Abstract
The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.
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- 2021
15. Author Response: Comparison of Ice Pack Test and Single-Fiber EMG Diagnostic Accuracy in Patients Referred for Myasthenic Ptosis
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Maria Pia Giannoccaro, Rocco Liguori, Giannoccaro M.P., and Liguori R.
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medicine.medical_treatment ,Ocular myasthenia ,Single fiber emg ,Diagnostic accuracy ,Electromyography ,03 medical and health sciences ,0302 clinical medicine ,Ptosis ,Myasthenia Gravis ,medicine ,Ice pack ,Blepharoptosis ,Humans ,In patient ,030212 general & internal medicine ,medicine.diagnostic_test ,business.industry ,Ice ,Blepharoptosi ,medicine.disease ,Test (assessment) ,Neurology (clinical) ,medicine.symptom ,Nuclear medicine ,business ,030217 neurology & neurosurgery ,Human - Abstract
We thank Dr. Silvestri for the comment on our article1 and agree that a relatively high proportion of patients showed discordant results between the ice pack test and single-fiber electromyography (SF-EMG) because they were observed in 15% of patients with a final diagnosis of ocular myasthenia (OM). Most of discordant cases were related to the negativity of the ice pack test in the presence of an altered SF-EMG result. One explanation could be the lack of repetition of the ice pack test, as we outlined in the discussion. Indeed, a previous study showed that repeated ice pack tests improved sensitivity by 34.6% compared with a single test.2 We also found that the repetition of the ice pack test in some patients increased its sensitivity and, therefore, the number of patients showing concordant results (unpublished data).
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- 2021
16. Antibodies to neuronal surface antigens in patients with a clinical diagnosis of neurodegenerative disorder
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Maria Pia Giannoccaro, Leslie Jacobson, Sabina Capellari, Giulia Perini, Veria Vacchiano, Diego Franciotta, Rocco Liguori, Matteo Gastaldi, Angela Vincent, Giovanni Rizzo, Alfredo Costa, Giannoccaro M.P., Gastaldi M., Rizzo G., Jacobson L., Vacchiano V., Perini G., Capellari S., Franciotta D., Costa A., Liguori R., and Vincent A.
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0301 basic medicine ,medicine.medical_specialty ,Immunology ,Population ,Hashimoto Disease ,Logistic regression ,Gastroenterology ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Autoimmune encephaliti ,Antigen ,Internal medicine ,Autoimmune dementia ,Encephaliti ,medicine ,Dementia ,Humans ,Prospective Studies ,Prospective cohort study ,education ,Autoantibodies ,Autoimmune encephalitis ,education.field_of_study ,biology ,Endocrine and Autonomic Systems ,business.industry ,Parkinsonism ,Neurodegenerative Diseases ,Neurodegenerative disorder ,medicine.disease ,Autoantibodie ,Prospective Studie ,030104 developmental biology ,Neuronal surface antibodie ,Antigens, Surface ,biology.protein ,Encephalitis ,Antibody ,business ,030217 neurology & neurosurgery ,Human - Abstract
Objectives Autoimmune encephalitis due to antibodies against neuronal surface antigens (NSA-Ab) frequently presents with cognitive impairment, often as the first and prevalent manifestation, but few studies have systematically assessed the frequency of NSA-Ab in consecutive patients with established neurodegenerative disorders. Methods We studied sera of 93 patients (41F, 52 M), aged 69.2 ± 9.4 years, with neurodegenerative conditions, and of 50 population controls aged over 60 years. Specific NSA-Abs were investigated by antigen-specific cell-based assays (CBAs). After testing, we evaluated the association between the NSA-Abs and clinical, CSF and radiological features. Results The patients included 13/93 (13.8%) who had specific antibodies to neuronal surface antigens: 6 GlyR, 3 GABAAR (1 also positive for AMPAR), 2 LGI1, 1 CASPR2 and 1 GABABR. One of the 50 controls (2%) was positive for NMDAR antibody and the others were negative on all tests (P = 0.020). No difference was observed in antibody frequency between patients presenting with parkinsonism and those presenting with dementia (P = 0.55); however, NSA-Ab were more frequent in those with unclassified forms of dementia (5/13, 38.5%) than in those with unclassified parkinsonism (2/9, 22.2%) or with classified forms of dementia (4/43, 9.3%) or parkinsonism (2/28, 7.1%) (P = 0.03). A logistic regression analysis demonstrated that an unclassified diagnosis (P = 0.02) and an irregular progression (P = 0.024) were predictors of seropositive status. Conclusions NSA-Abs are relatively frequent in patients with neurodegenerative disorders, particularly in those with an irregular disease progression of atypical clinical features, inconsistent with a recognized diagnosis. The significance of these antibodies and their possible primary or secondary roles need to be investigated in prospective studies.
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- 2021
17. Comparison of 123I-MIBG scintigraphy and phosphorylated α-synuclein skin deposits in synucleinopathies
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Giulia Giannini, Ernesto Cason, Vincenzo Donadio, Alex Incensi, Pietro Cortelli, Giovanni Rizzo, Maria Pia Giannoccaro, Giovanna Calandra-Buonaura, Rocco Liguori, Roberto Eleopra, Grazia Devigili, Giannoccaro M.P., Donadio V., Giannini G., Devigili G., Rizzo G., Incensi A., Cason E., Calandra Buonaura G., Eleopra R., Cortelli P., and Liguori R.
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0301 basic medicine ,Male ,Pathology ,Synucleinopathies ,Scintigraphy ,0302 clinical medicine ,Phosphorylation ,Skin ,medicine.diagnostic_test ,Heart ,Parkinson Disease ,Middle Aged ,3-Iodobenzylguanidine ,Autonomic ,Neurology ,alpha-Synuclein ,Female ,123I-MIBG ,Lewy Body Disease ,medicine.medical_specialty ,Differential diagnosi ,Alpha synuclein deposit ,03 medical and health sciences ,Atrophy ,parasitic diseases ,mental disorders ,Skin biopsy ,medicine ,Pure Autonomic Failure ,Humans ,Peripheral Nerves ,Pure autonomic failure ,Radionuclide Imaging ,Aged ,Lewy body ,Dementia with Lewy bodies ,business.industry ,Myocardium ,Biomarker ,Multiple System Atrophy ,medicine.disease ,nervous system diseases ,030104 developmental biology ,nervous system ,Neurology (clinical) ,Geriatrics and Gerontology ,Differential diagnosis ,Radiopharmaceuticals ,business ,030217 neurology & neurosurgery - Abstract
Introduction: Cardiac [123I]metaiodobenzylguanidine scintigraphy (123I-MIBG) is considered a useful test in differentiating multiple system atrophy (MSA) and Lewy body disorders (LBD), including idiopathic Parkinson's disease (IPD), dementia with Lewy bodies (DLB) and pure autonomic failure (PAF). The detection of skin nerve phosphorylated α-synuclein (p-α-syn) deposits could be an alternative marker in vivo. We sought to compare 123I-MIBG scintigraphy and skin biopsy findings in α-synucleinopathies. Methods: We studied 54 patients (7 DLB, 21 IPD, 13 PAF, 13 MSA) who underwent 123I-MIBG scintigraphy and skin biopsy to evaluate cardiac innervation and skin p-α-syn deposition, respectively. Results: Cardiac denervation was observed in 90.5% IPD, 100% DLB and PAF and in none of the MSA patients (P < 0.0001) whereas p-α-syn deposits were detected in all DLB and PAF, in 95.2% of IPD and 69.2% of MSA patients (P = 0.02). However, the analysis of skin structures disclosed a different distribution of the deposits in somatic subepidermal plexus and autonomic fibers among groups, showing that p-α-syn deposits rarely affected the autonomic fibers in MSA as opposed to LBD. Studying the p-α-syn deposition in autonomic nerves, concordance among I123-MIBG scintigraphy and skin biopsy results was observed in 100% of DLB and PAF, 95.2% IPD and 92.3% MSA patients. I123-MIBG scintigraphy and autonomic p-α-syn deposits analysis both showed a sensitivity of 97.5% and a specificity of 100% and 92.3%, respectively, in distinguishing LBD and MSA. Conclusion: Skin biopsy and 123-MIBG scintigraphy can be considered alternative tests for the differential diagnosis of IPD, PAF and DLB versus MSA.
- Published
- 2020
18. Immunotherapy in Narcolepsy
- Author
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Giombattista Sallemi, Giuseppe Plazzi, Maria Pia Giannoccaro, Rocco Liguori, and Fabio Pizza
- Subjects
medicine.medical_specialty ,Sleep disorder ,Neurology ,business.industry ,Autoimmunity ,Corticosteroid ,Immunotherapy ,Intravenous immunoglobulin ,Monoclonal antibodies ,Narcolepsy type 1 ,medicine.medical_treatment ,medicine.disease ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Autoimmune Process ,030220 oncology & carcinogenesis ,Diabetes mellitus ,Medicine ,Plasmapheresis ,Neurology (clinical) ,business ,Intensive care medicine ,030217 neurology & neurosurgery ,Narcolepsy - Abstract
Narcolepsy type 1 (NT1) is a chronic and disabling sleep disorder due to the loss of hypocretinergic neurons in the lateral hypothalamus pathophysiologically linked to an autoimmune process. Current treatment is symptomatic, and no cure is available to date. Immunotherapy is considered a promising future therapeutic option, and this review discusses the rationale for immunotherapy in narcolepsy, current evidences of its effects, outcome measures, and future directions. A limited number of case reports and uncontrolled small case series have reported the effect of different immunotherapies in patients with NT1. These studies were mainly based on the use of intravenous immunoglobulin (IVig), followed by corticosteroids, plasmapheresis, and monoclonal antibodies. Although initial reports showed an improvement of symptoms, particularly when patients were treated close to disease onset, other observations have not confirmed these results. Inadequate timing of treatment, placebo effects, and spontaneous improvement due to the natural disease course can account for these contrasting findings. Moreover, clear endpoints and standardized outcome measures have not been used and are currently missing in the pediatric population. On the basis of the available data, there are no enough evidences to support the use of immunotherapy in NT1. Randomized, controlled studies using clear endpoints and new outcome measures are needed to achieve a definitive answer about the usefulness of these treatments in narcolepsy.
- Published
- 2020
19. Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study
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Marco Zoccarato, Stefano Ricci, Luca Massacesi, Carla Arbasino, Luigi Zuliani, P. De Gaspari, M. Di Filippo, Federico Massa, Riccardo Di Iorio, S. Bova, Alessandro Barilaro, Diego Franciotta, Gregorio Spagni, Rocco Liguori, Amelia Evoli, Luana Benedetti, Laura Papetti, Marco Mauri, Enrico Marchioni, Silvia Casagrande, Sara Mariotto, Maria Pia Giannoccaro, Caterina Lapucci, Maurizio Versino, Massimiliano Valeriani, Michele Romoli, Federico Vigevano, Stefano Sartori, Margherita Nosadini, Bruno Giometto, Matteo Gastaldi, Sergio Ferrari, Gastaldi, M., Mariotto, S., Giannoccaro, M. P., Iorio, R., Zoccarato, M., Nosadini, M., Benedetti, L., Casagrande, S., Di Filippo, M., Valeriani, M., Ricci, S., Bova, S., Arbasino, C., Mauri, M., Versino, M., Vigevano, F., Papetti, L., Romoli, M., Lapucci, C., Massa, F., Sartori, S., Zuliani, L., Barilaro, A., De Gaspari, P., Spagni, G., Evoli, A., Liguori, R., Ferrari, S., Marchioni, E., Giometto, B., Massacesi, L., and Franciotta, D.
- Subjects
Male ,0302 clinical medicine ,Prednisone ,Retrospective Studie ,Receptors ,80 and over ,Infectious encephalitis ,030212 general & internal medicine ,Autoimmune encephalitis ,Child ,Neurons ,Aged, 80 and over ,Limbic encephalitis ,Middle Aged ,neuronal antibodies ,Immunohistochemistry ,Settore MED/26 - NEUROLOGIA ,Phenotype ,Neurology ,Child, Preschool ,diagnostic criteria ,immunotherapy ,Encephalitis ,Rituximab ,Female ,N-Methyl-D-Aspartate ,medicine.drug ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Hashimoto Disease ,Receptors, N-Methyl-D-Aspartate ,03 medical and health sciences ,Young Adult ,Aged ,Humans ,Infant ,Retrospective Studies ,Internal medicine ,Encephaliti ,medicine ,Preschool ,business.industry ,Retrospective cohort study ,Odds ratio ,Neuron ,medicine.disease ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,neuronal antibodie - Abstract
Background and purpose : Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients’ management was studied, focusing on the subgroupofAb-negative-AE. Methods: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). Results: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P=0.045), responded more frequently to treatments (92.3% vs. 65.6%, P 
- Published
- 2020
20. The First Historically Reported Italian Family with FTD/ALS Teaches a Lesson on C9orf72 RE: Clinical Heterogeneity and Oligogenic Inheritance
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Pasquale Montagna, Sabina Capellari, Piero Parchi, Giovanni Ambrosetto, Silvia Piras, Federico Oppi, Alfonsina Casalena, Maria Pia Giannoccaro, Anna Bartoletti-Stella, Rocco Liguori, Giannoccaro, Maria Pia, Bartoletti-Stella, Anna, Piras, Silvia, Casalena, Alfonsina, Oppi, Federico, Ambrosetto, Giovanni, Montagna, Pasquale, Liguori, Rocco, Parchi, Piero, and Capellari, Sabina
- Subjects
Adult ,Male ,0301 basic medicine ,Multifactorial Inheritance ,FTDALS1 ,03 medical and health sciences ,0302 clinical medicine ,C9orf72 gene ,C9orf72 ,mental disorders ,medicine ,Humans ,Dementia ,Genetic Testing ,Cognitive decline ,Amyotrophic lateral sclerosis ,Amyotrophic lateral sclerosi ,Adaptor Proteins, Signal Transducing ,Cerebral Cortex ,Genetics ,DNA Repeat Expansion ,Membrane Glycoproteins ,C9orf72 Protein ,business.industry ,General Neuroscience ,Amyotrophic Lateral Sclerosis ,Oligogenic Inheritance ,General Medicine ,Middle Aged ,medicine.disease ,Pedigree ,Psychiatry and Mental health ,Clinical Psychology ,030104 developmental biology ,ITM2B ,Schizophrenia ,Frontotemporal Dementia ,Mutation ,Female ,Geriatrics and Gerontology ,Trinucleotide repeat expansion ,business ,familial ALS/FTD ,030217 neurology & neurosurgery ,Frontotemporal dementia - Abstract
Background In 1969, Dazzi and Finizio reported the second observation of frontotemporal dementia (FTD) - amyotrophic lateral sclerosis (ALS) association in a large Italian kindred affected by an autosomal dominant form of ALS with high penetrance, frequent bulbar onset, and frequent cognitive decline. Objective To expand the original characterization of this family and report the link with the C9orf72 repeat expansion (RE). Methods We followed or reviewed the medical records of thirteen patients belonging to the original family and performed genetic analyses in four individuals. Results Eight patients presented with ALS, four with FTD, and one with schizophrenia. The C9orf72 RE was found in three patients but not in the healthy survivor. Additionally, we found a novel possible pathogenic variant in the ITM2B gene in one patient with a complex phenotype, associating movement disorders, psychiatric and cognitive features, deafness, and optic atrophy. The neuropathological examination of this patient did not show the classical features of ITM2B mutation related dementias suggesting that the putative pathogenic mechanism does not involve cellular mislocalization of the protein or the formation of amyloid plaques. Conclusion We showed that the original Italian pedigree described with FTD/ALS carries the C9orf72 RE. Moreover, the finding of an additional mutation in another dementia causing gene in a patient with a more complex phenotype suggests a possible role of genetic modifiers in the disease. Together with other reports showing the coexistence of mutations in multiple ALS/FTD causative genes in the same family, our study supports an oligogenic etiology of ALS/FTD.
- Published
- 2018
21. Efficacy and safety of rituximab therapy in patients with autoimmune neurological disorders
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Vincenzo Donadio, Maria Pia Giannoccaro, Patrizia Avoni, Rocco Liguori, and Veria Vacchiano
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Oncology ,medicine.medical_specialty ,Neurology ,Rituximab therapy ,business.industry ,Internal medicine ,medicine ,In patient ,Neurology (clinical) ,business - Published
- 2021
22. Application of the APE2 and RITE2 scores in patients presenting with cognitive dysfunction
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Maria Pia Giannoccaro, Patrizia Avoni, Rocco Liguori, Paolo Tinuper, and Filippo Salvi
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medicine.medical_specialty ,Neurology ,business.industry ,Physical therapy ,Medicine ,Cognition ,In patient ,Neurology (clinical) ,business - Published
- 2021
23. Neuronal surface antibodies are common in children with narcolepsy and active movement disorders
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Fabio Pizza, Leslie Jacobson, Angela Vincent, Maria Pia Giannoccaro, Rocco Liguori, Giuseppe Plazzi, Giannoccaro M.P., Pizza F., Jacobson L., Liguori R., Plazzi G., and Vincent A.
- Subjects
Pediatrics ,medicine.medical_specialty ,Movement disorders ,Cataplexy ,Tics ,Excessive daytime sleepiness ,neuroimmunology ,03 medical and health sciences ,0302 clinical medicine ,PANDAS ,medicine ,International Classification of Sleep Disorders ,Sleep disorder ,business.industry ,medicine.disease ,autoimmune encephalitis ,movement disorders ,sleep disorders ,Psychiatry and Mental health ,Surgery ,movement disorder ,Neurology (clinical) ,autoimmune encephaliti ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Narcolepsy - Abstract
Narcolepsy type 1 (NT1) is a chronic sleep disorder of suspected autoimmune aetiology.1 In children, a complex movement disorder, characterised by typical cataplexy and other hypotonic (‘negative’) motor features and also by ‘active’ motor phenomena, was described.2 These motor phenomena recall post-streptococcal autoimmune disorders such as Sydenham’s chorea, tics and paediatric autoimmune neuropsychiatric disorders sssociated with streptococcal infections (PANDAS), and the movements in patients with antibodies to neuronal surface antigens (NSAbs).3 We investigated movement disorders and NSAbs in NT1. We retrospectively assessed consecutive patients with drug-naive NT1 seen at the Bologna Sleep Centre within the last year at the time of the study. The patients were diagnosed according to the International Classification of Sleep Disorders (ICSD), third edition. Serum was stored at −80°C. Motor phenomena were studied and scored retrospectively,2 using the video recordings routinely performed on first admission, on the day of blood sampling. Cell-based assays for specific antigens were tested on NT1 and control sera. See online supplemental file 1 for more details. ### Supplementary data [jnnp-2020-323638supp001.pdf] The Ethical Committee approved the study (Protocol 17009). Consent to participate was collected from patients or from parents. ### Statistical analysis Continuous variables, not normally distributed, were compared using the Mann-Whitney U test or the Kruskal-Wallis test. Categorical data were analysed with Fisher’s exact test. ### Patients and clinical features There were 58 patients (21 F, 37 M), aged 8–66 years (median 32.5), with 22 under 18 years. The median age at onset (either of excessive daytime sleepiness (EDS) or cataplexy) was 14.5 years (range, 4–62). The time gap between …
- Published
- 2020
24. Post-ganglionic autonomic neuropathy associated with anti-glutamic acid decarboxylase antibodies
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Vincenzo Donadio, Roberto D'Angelo, Rocco Liguori, Maria Pia Giannoccaro, Alex Incensi, Rita Rinaldi, E. Fileccia, Fileccia, E, Rinaldi, R., Liguori, R., Incensi, A., D’Angelo, R., Giannoccaro, Mp., and Donadio, V.
- Subjects
Male ,medicine.medical_specialty ,Neurology ,Anti-GAD antibodie ,Glutamate decarboxylase ,Neural Conduction ,Gastroenterology ,Endocrine and Autonomic System ,Autonomic neuropathy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,Skin biopsy ,Humans ,Medicine ,Autoantibodies ,medicine.diagnostic_test ,Glutamate Decarboxylase ,Endocrine and Autonomic Systems ,business.industry ,Middle Aged ,Anti-glutamic acid decarboxylase antibodie ,medicine.disease ,Pathophysiology ,Post-ganglionic autonomic neuropathy ,Autonomic nervous system ,Endocrinology ,Peripheral neuropathy ,Autonomic Nervous System Diseases ,030220 oncology & carcinogenesis ,Autonomic Fibers, Postganglionic ,Cholinergic ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Purpose: Antibodies to glutamic acid decarboxylase (GAD-Abs) have been associated with several conditions, rarely involving the autonomic nervous system. Here, we describe two patients complaining of autonomic symptoms in whom a post-ganglionic autonomic neuropathy has been demonstrated in association with significantly elevated serum and CSF GAD-Abs levels. Methods: Patients underwent nerve conduction studies, sympathetic skin response testing, evaluation of autonomic control of the cardiovascular system and skin biopsy. Also, serum screening to exclude predisposing causes of peripheral neuropathy was performed. Anti-GAD65 antibodies were evaluated in serum and CSF. Results: GAD-Abs titer was increased in both serum and CSF in both patients. Sympathetic skin response was absent and skin biopsy revealed a non-length-dependent small-fiber neuropathy with sympathetic cholinergic and adrenergic post-ganglionic damage in both patients. Nerve conduction studies and evaluation of autonomic control of the cardiovascular system were normal in both patients. Both patients were treated with steroids with good, but partial, (patient 2) recovery of the autonomic dysfunctions. Conclusions: Although the pathophysiological mechanisms involved are not fully defined, GAD-abs positivity in serum and CSF should be searched in patients with autonomic neuropathy when no other acquired causes are evident. This positivity may help to clarify autoimmune etiology and, subsequently, to consider immunomodulatory treatment.
- Published
- 2016
25. Sensitivity and specificity of single-fibre EMG in the diagnosis of ocular myasthenia varies accordingly to clinical presentation
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Corrado Zanesini, Patrizia Avoni, Vitantonio Di Stasi, Maria Pia Giannoccaro, Vincenzo Donadio, Rocco Liguori, Giannoccaro, Maria Pia, Di Stasi, Vitantonio, Zanesini, Corrado, Donadio, Vincenzo, Avoni, Patrizia, and Liguori, Rocco
- Subjects
Adult ,Male ,medicine.medical_specialty ,Neurology ,Adolescent ,Ocular myasthenia ,SF-EMG ,Electromyography ,Gastroenterology ,Sensitivity and Specificity ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Sensitivity ,Ptosis ,Internal medicine ,Myasthenia Gravis ,medicine ,Humans ,030212 general & internal medicine ,Neuroradiology ,Aged ,Diplopia ,Aged, 80 and over ,medicine.diagnostic_test ,Orbicularis oculi muscle ,business.industry ,Middle Aged ,medicine.disease ,Oculomotor Muscles ,Specificity ,Female ,Neurology (clinical) ,medicine.symptom ,Presentation (obstetrics) ,business ,030217 neurology & neurosurgery - Abstract
Single-fibre electromyography (SF-EMG) is considered as the most sensitive test for the diagnosis of MG. However, previous studies had limitations, such as a retrospective design, non-consecutive sampling, incorporation bias or were performed in small or mixed populations. Our aims were to determine the diagnostic sensitivity and specificity of SF-EMG of the orbicularis oculi in OMG and the utility of this test in relation to patients' clinical presentation.We studied 232 consecutive patients referred to the SF-EMG laboratory for a suspected OMG. Stimulated SF-EMG was performed on the orbicularis oculi muscle. OMG was diagnosed in 165 cases and other disorders (OD) in 67. SF-EMG showed a sensitivity of 0.79 (95% CI 0.73–0.85) and a specificity of 0.80 (95% CI 0.71–0.90). False negative results were associated with mild symptoms and with isolated diplopia. Comparison of the diagnostic yield among patients with different clinical presentations showed a similar diagnostic accuracy of SF-EMG in patients with ptosis and in patients with ptosis and diplopia, significantly higher than in patients with isolated diplopia (P
- Published
- 2019
26. Combined brain positron emission tomography/magnetic resonance imaging in <scp>GABA</scp> A receptor encephalitis
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V. Allegri, Veria Vacchiano, Maria Pia Giannoccaro, R. P. Napolitano, L. Spinardi, Rita Rinaldi, Rocco Liguori, Vacchiano V., Giannoccaro M.P., Napolitano R.P., Liguori R., Allegri V., Rinaldi R., and Spinardi L.
- Subjects
Autoimmune encephalitis ,medicine.diagnostic_test ,GABAA receptor ,business.industry ,Magnetic resonance imaging ,medicine.disease ,GABA ,PET/MRI ,Nuclear magnetic resonance ,Neurology ,R antibodie ,medicine ,Brain positron emission tomography ,Neurology (clinical) ,autoimmune encephaliti ,business ,Encephalitis - Abstract
NA
- Published
- 2019
27. Behaviour and neuropathology in mice injected with human contactin-associated protein 2 antibodies
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Leslie Jacobson, Gennaro Prota, Maria Pia Giannoccaro, Angela Vincent, Vincenzo Cerundolo, Maria Isabel Leite, Rocco Liguori, Ester Coutinho, David A. Menassa, Bethan Lang, Giannoccaro, Maria Pia, Menassa, David A, Jacobson, Leslie, Coutinho, Ester, Prota, Gennaro, Lang, Bethan, Leite, M Isabel, Cerundolo, Vincenzo, Liguori, Rocco, Vincent, Angela, and Kullmann, D
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,medicine.medical_specialty ,Cell Adhesion Molecules, Neuronal ,microglia activation ,Hippocampus ,Neuropathology ,Hippocampal formation ,Blood–brain barrier ,Open field ,Immunoglobulin G ,Mice ,03 medical and health sciences ,0302 clinical medicine ,astrocyte ,Cell Movement ,Internal medicine ,medicine ,Animals ,Humans ,Lymphocytes ,Cells, Cultured ,Autoantibodies ,Neurons ,passive transfer ,Behavior, Animal ,biology ,Microglia ,animal model ,Brain ,Spontaneous alternation ,CASPR2 antibodie ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Blood-Brain Barrier ,biology.protein ,Female ,Neurology (clinical) ,Neuroglia ,Proto-Oncogene Proteins c-fos ,Injections, Intraperitoneal ,030217 neurology & neurosurgery - Abstract
Serum antibodies that bind to the surface of neurons or glia are associated with a wide range of rare but treatable CNS diseases. In many, if not most instances, the serum levels are higher than CSF levels yet most of the reported attempts to reproduce the human disease in mice have used infusion of antibodies into the mouse cerebral ventricle(s) or intrathecal space. We used the intraperitoneal route and injected purified plasma IgG from either a CASPR2-antibody-positive patient (n = 10 mice) or healthy individual (n = 9 mice) daily for 8 days. Lipopolysaccharide was injected intraperitoneally on Day 3 to cause a temporary breach in the blood brain barrier. A wide range of baseline behaviours, including tests of locomotion, coordination, memory, anxiety and social interactions, were established before the injections and tested from Day 5 until Day 11. At termination, brain tissue was analysed for human IgG, CASPR2 and c-fos expression, lymphocyte infiltration, and neuronal, astrocytic and microglial markers. Mice exposed to CASPR2-IgG, compared with control-IgG injected mice, displayed reduced working memory during the continuous spontaneous alternation test with trends towards reduced short-term and long-term memories. In the open field tests, activities were not different from controls, but in the reciprocal social interaction test, CASPR2-IgG injected mice showed longer latency to start interacting, associated with more freezing behaviour and reduced non-social activities of rearing and grooming. At termination, neuropathology showed more IgG deposited in the brains of CASPR2-IgG injected mice, but a trend towards increased CASPR2 expression; these results were mirrored in short-term in vitro experiments where CASPR2-IgG binding to hippocampal neurons and to CASPR2-transfected HEK cells led to some internalization of the IgG, but with a trend towards higher surface CASPR2 expression. Despite these limited results, in the CASPR2-IgG injected mouse brains there was increased c-fos expression in the piriform-entorhinal cortex and hypothalamus, and a modest loss of Purkinje cells. There was also increased microglia density, morphological changes in both microglia and astrocytes and raised complement C3 expression on astrocytes, all consistent with glial activation. Patients with CASPR2 antibodies can present with a range of clinical features reflecting central, autonomic and peripheral dysfunction. Although the behavioural changes in mice were limited to social interactions and mild working-memory defects, the neuropathological features indicate potentially widespread effects of the antibodies on different brain regions.
- Published
- 2019
28. Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1
- Author
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Nicola De Stefano, Rocco Liguori, Roberto Poda, David Neil Manners, Antonio Giorgio, Patrizia Avoni, Stefania Evangelisti, Federico Oppi, Maria Pia Giannoccaro, Caterina Tonon, Claudia Testa, Laura Ludovica Gramegna, Raffaele Lodi, Stefano Zanigni, Zanigni, Stefano, Evangelisti, Stefania, Giannoccaro, Maria Pia, Oppi, Federico, Poda, Roberto, Giorgio, Antonio, Testa, Claudia, Manners, David Neil, Avoni, Patrizia, Gramegna, Laura Ludovica, De Stefano, Nicola, Lodi, Raffaele, Tonon, Caterina, and Liguori, Rocco
- Subjects
Male ,0301 basic medicine ,Pathology ,Neurology ,Neuropsychological Tests ,Severity of Illness Index ,Brain mapping ,lcsh:RC346-429 ,0302 clinical medicine ,Nuclear Medicine and Imaging ,Myotonic Dystrophy ,Gray Matter ,cortical thickne ,VBM ,cortical thickness ,DTI ,myotonic dystrophy type 1 ,TBSS ,Neurology (clinical) ,Radiology, Nuclear Medicine and Imaging ,Cognitive Neuroscience ,Brain Mapping ,medicine.diagnostic_test ,Myotonin-protein kinase ,Neuropsychology ,Regular Article ,Middle Aged ,Magnetic Resonance Imaging ,White Matter ,medicine.anatomical_structure ,lcsh:R858-859.7 ,Female ,Radiology ,Psychology ,Adult ,musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,lcsh:Computer applications to medicine. Medical informatics ,Myotonic dystrophy ,Myotonin-Protein Kinase ,Statistics, Nonparametric ,White matter ,03 medical and health sciences ,Imaging, Three-Dimensional ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,lcsh:Neurology. Diseases of the nervous system ,Magnetic resonance imaging ,medicine.disease ,030104 developmental biology ,Case-Control Studies ,Trinucleotide Repeat Expansion ,Trinucleotide repeat expansion ,030217 neurology & neurosurgery - Abstract
Background Myotonic dystrophy type 1 (DM1) represents a multisystemic disorder in which diffuse brain white and gray matter alterations related to clinical and genetic features have been described. We aimed to evaluate in the brain of adult patients with DM1 (i) white and gray matter differences, including cortical-subcortical gray matter volume and cortical thickness and (ii) their correlation with clinical disability, global neuropsychological performance and triplet expansion. Methods We included 24 adult genetically-confirmed DM1 patients (14 males; age: 38.5 ± 11.8 years) and 25 age- and sex-matched healthy controls (14 males; age: 38.5 ± 11.3 years) who underwent an identical brain MR protocol including high-resolution 3D T1-weighted, axial T2 FLAIR and DTI sequences. All patients underwent an extensive clinical and neuropsychological evaluation. Voxel-wise analyses of white matter, performed by using Tract Based Spatial Statistics, and of gray matter, with Voxel-based Morphometry and Cortical Thickness, were carried out in order to test for differences between patients with DM1 and healthy controls (p, Highlights • We investigated DM1 brain abnormalities with TBSS, VBM and cortical thickness analysis. • White matter lesion refilling has been performed to improve voxel-wise analyses. • All patients have been evaluated using a clinical scale created ad hoc for DM1. • DM1 patients present diffuse white and cortical-subcortical gray matter disruption. • White matter differences are correlated with clinical and genetic features.
- Published
- 2016
29. Skin nerve misfolded α-synuclein in pure autonomic failure and Parkinson disease
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Rocco Liguori, Maria Pia Giannoccaro, Vincenzo Donadio, Pietro Cortelli, Agostino Baruzzi, Cristina Piccinini, and Alex Incensi
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,animal diseases ,Nerve fiber ,Disease ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,medicine ,heterocyclic compounds ,Pure autonomic failure ,Alpha-synuclein ,medicine.diagnostic_test ,business.industry ,bacterial infections and mycoses ,medicine.disease ,nervous system diseases ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Neurology ,chemistry ,Skin biopsy ,Synuclein ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Objective To characterize the expression in skin nerves of native (n-syn) and misfolded phosphorylated (p-syn) α-synucleins in pure autonomic failure (PAF) and idiopathic Parkinson disease (IPD). The specific aims were to (1) define the importance of n-syn and p-syn as disease biomarkers and (2) ascertain differences in abnormal synuclein skin nerve deposits. Methods We studied 30 patients, including 16 well-characterized IPD patients and 14 patients fulfilling PAF diagnostic criteria, and 15 age-matched controls. Subjects underwent skin biopsy from proximal (ie, cervical) and distal (ie, thigh and leg) sites to study small nerve fiber and intraneural n-syn and p-syn. Results PAF and IPD showed length-dependent somatic and autonomic small fiber loss, more severely expressed in patients with higher p-syn load. n-syn was similarly expressed in both groups of patients and controls. By contrast, p-syn was not evident in any skin sample of controls but was found in all PAF and IPD patients, although with different skin innervation. In addition, abnormal α-synuclein deposits were found in all analyzed skin samples in PAF but in only 49% of samples with a higher positivity rate at the proximal site in IPD. Interpretation (1) Intraneural p-syn was a reliable in vivo marker of PAF and IPD; (2) neuritic p-syn inclusions differed in PAF and IPD, suggesting a different underlying pathogenesis; (3) when searching for abnormal p-syn deposits in skin nerves, the site of analysis is irrelevant in PAF but it is critical in IPD.
- Published
- 2015
30. Mitochondrial dysfunction in myotonic dystrophy type 1
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Caterina Tonon, David Neil Manners, Roberto Poda, Federico Oppi, Claudio Bianchini, Laura Ludovica Gramegna, Raffaele Lodi, Stefano Zanigni, Rocco Liguori, Patrizia Avoni, Maria Pia Giannoccaro, Claudia Testa, Stefania Evangelisti, Gramegna, Laura Ludovica, Giannoccaro, Maria Pia, Manners, David Neil, Testa, Claudia, Zanigni, Stefano, Evangelisti, Stefania, Bianchini, Claudio, Oppi, Federico, Poda, Roberto, Avoni, Patrizia, Lodi, Raffaele, Liguori, Rocco, and Tonon, Caterina
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Mitochondrial Diseases ,Proton Magnetic Resonance Spectroscopy ,Myotonic dystrophy ,Severity of Illness Index ,03 medical and health sciences ,Lateral ventricles ,Young Adult ,0302 clinical medicine ,Adenosine Triphosphate ,In vivo ,Internal medicine ,medicine ,Humans ,Myotonic Dystrophy ,Magnetic resonance imaging (MRI) ,Muscle, Skeletal ,Gene ,Pathological ,Exercise ,Genetics (clinical) ,Aged ,business.industry ,Myotonic dystrophy type 1 ,Skeletal muscle ,Brain ,Organ Size ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Pathophysiology ,In vitro ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Neurology ,Lower Extremity ,Pediatrics, Perinatology and Child Health ,Brain proton MR spectroscopy ,Muscle phosphorous MR spectroscopy ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
The pathophysiological mechanism linking the nucleotide expansion in the DMPK gene to the clinical manifestations of myotonic dystrophy type 1 (DM1) is still unclear. In vitro studies demonstrate DMPK involvement in the redox homeostasis of cells and the mitochondrial dysfunction in DM1, but in vivo investigations of oxidative metabolism in skeletal muscle have provided ambiguous results and have never been performed in the brain. Twenty-five DM1 patients (14M, 39 ± 11years) underwent brain proton MR spectroscopy (1H-MRS), and sixteen cases (9M, 40 ± 13 years old) also calf muscle phosphorus MRS (31P-MRS). Findings were compared to those of sex- and age-matched controls. Eight DM1 patients showed pathological increase of brain lactate and, compared to those without, had larger lateral ventricles (p
- Published
- 2018
31. Skin biopsy and I-123 MIBG scintigraphy findings in idiopathic Parkinson's disease and parkinsonism: A comparative study
- Author
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Sabina Capellari, Ernesto Cason, Giorgio Treglia, Alex Incensi, Maria Pia Giannoccaro, Paolo Martinelli, Vitantonio Di Stasi, Cesa Scaglione, Vincenzo Donadio, Rocco Liguori, and Fabio Pizza
- Subjects
Denervation ,medicine.medical_specialty ,Parkinson's disease ,integumentary system ,medicine.diagnostic_test ,business.industry ,Concordance ,Parkinsonism ,I 123 mibg ,Disease ,bacterial infections and mycoses ,medicine.disease ,Scintigraphy ,Neurology ,Skin biopsy ,medicine ,Neurology (clinical) ,Radiology ,business - Abstract
Background 123I-meta-iodobenzylguanidine (123I-MIBG) myocardial scintigraphy is considered reliable in differentiating idiopathic Parkinson's disease (IPD) from other parkinsonisms, but it is biased by pharmacological treatments. Skin biopsy is not influenced by therapy and has disclosed skin denervation in IPD. Our aims were to compare 123I-MIBG scintigraphy and skin biopsy findings in IPD and parkinsonisms to (1) verify whether myocardial and skin denervations are linked; (2) explore the simultaneous extent of the autonomic dysfunction. Methods We studied 22 IPD and 11 parkinsonism patients by means of 123I-MIBG scintigraphy and skin biopsies. Results In the IPD group, both 123I-MIBG scintigraphy and skin biopsy results were abnormal in 91% of patients, showing concordance in 82% of cases. In parkinsonisms, results of both tests were normal in all patients. Conclusion (1) Skin biopsy and 123I-MIBG scintigraphy provide comparable results; (2) in IPD, autonomic dysfunctions are often simultaneously widespread at cardiac and skin branches. © 2015 International Parkinson and Movement Disorder Society
- Published
- 2015
32. Multiple variants in families with amyotrophic lateral sclerosis and frontotemporal dementia related to C9orf72 repeat expansion: further observations on their oligogenic nature
- Author
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Silvia Piras, Rocco Liguori, Patrizia De Massis, Sabina Capellari, Federico Oppi, Annalisa Pession, Anna Bartoletti-Stella, Elena Pasini, Michelangelo Stanzani-Maserati, Maria Pia Giannoccaro, Piero Parchi, Simone Baiardi, Patrizia Avoni, Giannoccaro, Maria Pia, Bartoletti-Stella, Anna, Piras, Silvia, Pession, Annalisa, De Massis, Patrizia, Oppi, Federico, Stanzani-Maserati, Michelangelo, Pasini, Elena, Baiardi, Simone, Avoni, Patrizia, Parchi, Piero, Liguori, Rocco, Capellari, Sabina, DIPARTIMENTO DI FARMACIA E BIOTECNOLOGIE, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, and Da definire
- Subjects
Male ,0301 basic medicine ,Heterozygote ,Multifactorial Inheritance ,Pedigree chart ,Biology ,Severity of Illness Index ,TARDBP ,03 medical and health sciences ,Superoxide Dismutase-1 ,0302 clinical medicine ,C9orf72 ,mental disorders ,medicine ,Humans ,Family ,Amyotrophic lateral sclerosis ,Aged ,Genetics ,DNA Repeat Expansion ,TYROBP ,C9orf72 Protein ,Parkinsonism ,Amyotrophic Lateral Sclerosis ,ALS ,C9orf72 repeat expansion ,FTD ,Oligogenic ,Neurology ,Neurology (clinical) ,Middle Aged ,medicine.disease ,Phenotype ,nervous system diseases ,DNA-Binding Proteins ,030104 developmental biology ,Frontotemporal Dementia ,RNA-Binding Protein FUS ,Female ,Trinucleotide repeat expansion ,030217 neurology & neurosurgery ,Frontotemporal dementia - Abstract
none 13 no Italian Ministry of Research RFO, Fondazione del Monte, Fondazione Gino Galletti to SC, PP, RL and AIRAlzh Onlus-COOP Italia to ABS. The C9orf72 repeat expansion (RE) is one of the most frequent causative mutations of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, it is still unclear how the C9orf72 RE can lead to a heterogeneous phenotype. Several reports have shown the coexistence of mutations in multiple ALS/FTD causative genes in the same family, suggesting an oligogenic etiology for ALS and FTD. Our aim was to investigate this phenomenon in an Italian group of ALS/FTD pedigrees carrying the C9orf72 RE. We included 11 subjects from 11 pedigrees with ALS/FTD and the C9orf72 RE. Mutation screening of FUS, SOD1 and TARDBP genes was performed by direct sequencing. A dementia-specific custom-designed targeted next-generation sequencing panel was used for screening dementia-associated genes mutations. We found genetic variants in additional ALS or dementia-related genes in four pedigrees, including the p.V47A variant in the TYROBP gene. As a group, double mutation carriers displayed a tendency toward a younger age at onset and a higher frequency of positive familiar history and of parkinsonism. Our observation supports the hypothesis that the co-presence of mutations in different genes may be relevant for the clinical expression of ALS/FTD and of their oligogenic nature. mixed Giannoccaro, Maria Pia; Bartoletti-Stella, Anna; Piras, Silvia; Pession, Annalisa; De Massis, Patrizia; Oppi, Federico; Stanzani-Maserati, Michelangelo; Pasini, Elena; Baiardi, Simone; Avoni, Patrizia; Parchi, Piero; Liguori, Rocco; Capellari, Sabina Giannoccaro, Maria Pia; Bartoletti-Stella, Anna; Piras, Silvia; Pession, Annalisa; De Massis, Patrizia; Oppi, Federico; Stanzani-Maserati, Michelangelo; Pasini, Elena; Baiardi, Simone; Avoni, Patrizia; Parchi, Piero; Liguori, Rocco; Capellari, Sabina
- Published
- 2017
33. Antibodies against hypocretin receptor 2 are rare in narcolepsy
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Fabio Pizza, Patrick Waters, Giuseppe Plazzi, Maria Pia Giannoccaro, Angela Vincent, Rocco Liguori, Giannoccaro, Maria Pia, Waters, Patrick, Pizza, Fabio, Liguori, Rocco, Plazzi, Giuseppe, and Vincent, Angela
- Subjects
Adult ,Male ,0301 basic medicine ,Adolescent ,narcolepsy ,Antibodies ,HCRTR2 ,antibodies ,autoimmune ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Orexin Receptors ,Physiology (medical) ,medicine ,Humans ,Child ,Receptor ,Orexins ,Kidney ,biology ,business.industry ,Vaccination ,medicine.disease ,Primary and secondary antibodies ,Titer ,030104 developmental biology ,medicine.anatomical_structure ,antibodie ,Influenza Vaccines ,Case-Control Studies ,Immunoglobulin G ,Immunology ,biology.protein ,Female ,Neurology (clinical) ,Antibody ,business ,030217 neurology & neurosurgery ,Narcolepsy - Abstract
Study Objectives Recently, antibodies to the hypocretin receptor 2 (HCRTR2-Abs) were reported in a high proportion of narcolepsy patients who developed the disease following Pandemrix® vaccination. We tested a group of narcolepsy patients for the HCRTR2-Abs using a newly established cell-based assay. Methods Sera from 50 narcolepsy type 1 (NT1) and 11 narcolepsy type 2 (NT2) patients, 22 patients with other sleep disorders, 15 healthy controls, and 93 disease controls were studied. Cerebrospinal fluid (CSFs) from three narcoleptic patients were subsequently included. Human embryonic kidney cells were transiently transfected with human HCRTR2, incubated with patients’ sera for 1 hr at 1:20 dilution and then fixed. Binding of antibodies was detected by fluorescently labeled secondary antibodies to human immunoglobulin G (IgG) and the different IgG subclasses. A nonlinear visual scoring system was used from 0 to 4; samples scoring ≥1 were considered positive. Results Only 3 (5%) of 61 patients showed a score ≥1, one with IgG1- and two with IgG3-antibodies, but titers were low (1:40–1:100). CSFs from these patients were negative. The three positive patients included one NT1 case with associated psychotic features, one NT2 patient, and an NT1 patient with normal hypocretin CSF levels. Conclusions Low levels of IgG1 or IgG3 antibodies against HCRTR2 were found in 3 of 61 patients with narcolepsy, although only 1 presented with full-blown NT1. HCRTR2-Abs are not common in narcolepsy unrelated to vaccination.
- Published
- 2017
34. Mitochondrial DNA and primary mitochondrial dysfunction in Parkinson's disease
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Valerio Carelli, Chiara La Morgia, Giovanni Rizzo, Maria Pia Giannoccaro, Giannoccaro, Maria Pia, La Morgia, Chiara, Rizzo, Giovanni, and Carelli, Valerio
- Subjects
0301 basic medicine ,Mitochondrial DNA ,Mitochondrial Diseases ,PINK1 ,mitochondrial DNA ,Mitochondrion ,Biology ,Human mitochondrial genetics ,DNA, Mitochondrial ,Parkin ,03 medical and health sciences ,0302 clinical medicine ,Mitophagy ,medicine ,Humans ,quality control ,parkinsonism ,Genetics ,mtDNA ,Parkinsonism ,Neurodegeneration ,medicine.disease ,Parkinson disease ,030104 developmental biology ,mitophagy ,Neurology ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
In 1979, it was observed that parkinsonism could be induced by a toxin inhibiting mitochondrial respiratory complex I. This initiated the long-standing hypothesis that mitochondrial dysfunction may play a key role in the pathogenesis of Parkinson's disease (PD). This hypothesis evolved, with accumulating evidence pointing to complex I dysfunction, which could be caused by environmental or genetic factors. Attention was focused on the mitochondrial DNA, considering the occurrence of mutations, polymorphic haplogroup-specific variants, and defective mitochondrial DNA maintenance with the accumulation of multiple deletions and a reduction of copy number. Genetically determined diseases of mitochondrial DNA maintenance frequently manifest with parkinsonism, but the age-related accumulation of somatic mitochondrial DNA errors also represents a major driving mechanism for PD. Recently, the discovery of the genetic cause of rare inherited forms of PD highlighted an extremely complex homeostatic control over mitochondria, involving their dynamic fission/fusion cycle, the balancing of mitobiogenesis and mitophagy, and consequently the quality control surveillance that corrects faulty mitochondrial DNA maintenance. Many genes came into play, including the PINK1/parkin axis, but also OPA1, as pieces of the same puzzle, together with mitochondrial DNA damage, complex I deficiency and increased oxidative stress. The search for answers will drive future research to reach the understanding necessary to provide therapeutic options directed not only at limiting the clinical evolution of symptoms but also finally addressing the pathogenic mechanisms of neurodegeneration in PD. © 2017 International Parkinson and Movement Disorder Society.
- Published
- 2017
35. Paraneoplastic cerebellar degeneration and lambert-eaton myasthenia in a patient with merkel cell carcinoma and voltage-gated calcium channel antibodies
- Author
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Maria Pia Foschini, Maria Pia Giannoccaro, Bethan Lang, Angela Vincent, Lucia Pavolucci, Patrizia Avoni, Giulia Giannini, Rocco Liguori, Paolo Tinuper, Pavolucci, Lucia, Giannini, Giulia, Giannoccaro, Maria Pia, Foschini, Maria Pia, Lang, Bethan, Avoni, Patrizia, Tinuper, Paolo, Vincent, Angela, and Liguori, Rocco
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Ataxia ,Lung Neoplasms ,Physiology ,Lambert-Eaton myasthenia ,Paraneoplastic Cerebellar Degeneration ,Lesion ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Merkel cell carcinoma ,0302 clinical medicine ,Calcium Channels, N-Type ,Physiology (medical) ,Cerebellar Degeneration ,Medicine ,Humans ,Aged ,Autoantibodies ,Diplopia ,business.industry ,Paraneoplastic cerebellar degeneration ,medicine.disease ,Neuroendocrine neoplasm ,Carcinoma, Merkel Cell ,Axilla ,Lambert-Eaton Myasthenic Syndrome ,medicine.anatomical_structure ,Cerebellar degeneration ,Paraneoplastic syndrome ,Neurology (clinical) ,Small Cell Lung Carcinoma ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Voltage-gated calcium channel antibodie - Abstract
Introduction Merkel cell carcinoma is a rare cutaneous, aggressive tumor. Although it shares many neuroendocrine features with small cell lung carcinoma, it has only occasionally been reported with paraneoplastic neurological syndromes. Methods A healthy 67-year-old man developed acute ataxia, vertigo, and nausea. Subsequently he also developed dysarthria, diplopia, xerostomia, fatigability and progressive anorexia. He underwent a full diagnostic workup and was found to have a high titer of voltage-gated calcium channel antibodies in serum and cerebrospinal fluid, neurophysiological findings compatible with Lambert-Eaton myasthenia and neurological signs compatible with cerebellar degeneration. Results A positron emission tomography study revealed a hypermetabolic lesion in the axilla, subsequently biopsied and consistent with Merkel cell carcinoma. Conclusions In most previous reports, neurological symptoms preceded the Merkel cell carcinoma diagnosis, and the primary localization was in lymph nodes. This tumor should be considered in patients with paraneoplastic syndrome, and particularly Lambert-Eaton myasthenia after exclusion of small cell lung carcinoma. Muscle Nerve 56: 998–1000, 2017
- Published
- 2016
36. Sleep disorders in patients with spinal cord injury
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Fabio Pizza, Giuseppe Plazzi, Stefano Boriani, Keivan Kaveh Moghadam, Angela Morreale, Rocco Liguori, Maria Pia Giannoccaro, Nadir M. Maraldi, Patrizia Avoni, M. P. Giannoccaro, K. K. Moghadam, F. Pizza, S. Boriani, N. M. Maraldi, P. Avoni, A. Morreale, R. Liguori, and G. Plazzi
- Subjects
Sleep Wake Disorders ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Heart disease ,etiology/physiopathology/therapy, Sleep Disorder ,Population ,Health outcomes ,Poor quality ,etiology/physiopathology/therapy ,Sleep Apnea Syndromes ,Physiology (medical) ,Humans ,Medicine ,In patient ,education ,Intensive care medicine ,Spinal cord injury ,Spinal Cord Injuries ,education.field_of_study ,business.industry ,Humans, Sleep Apnea Syndrome ,complications/physiopathology ,medicine.disease ,Sleep Disorders ,etiology/physiopathology ,Sleep in non-human animals ,Pathophysiology ,Neurology ,etiology/physiopathology, Spinal Cord Injurie ,Physical therapy ,Neurology (clinical) ,business - Abstract
Sleep disturbances are globally more frequent in patients with spinal cord injury (SCI) than in the able-bodied population, and could contribute to dysfunction and poor quality of life in these patients. Specific sleep disorders may also contribute to negative health outcomes enhancing cardiovascular risk in a condition that per se increases heart disease related mortality. This review focuses on prevalence, features and treatment of sleep disorders in SCI. Although data on these subjects have been produced, reports on pathophysiology, consequences and treatment of sleep disorders are scarce or contradictory and more studies are required.
- Published
- 2013
37. Sleep and movement disorders
- Author
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Giuseppe Plazzi, Elena Antelmi, Maria Pia Giannoccaro, M. P. Giannoccaro, E. Antelmi, and G. Plazzi
- Subjects
Sleep Wake Disorders ,Parkinson's disease ,Movement disorders ,Rapid eye movement sleep ,Excessive daytime sleepiness ,Non-rapid eye movement sleep ,status dissociatus ,medicine ,Movement Disorder ,Humans ,Dementia ,Sleep Wake Disorder ,sleep ,Sleep disorder ,Movement Disorders ,business.industry ,movement disorders ,rapid eye movement sleep behavior disorder ,Neurology (clinical) ,Neurology ,medicine.disease ,CLOCK ,status dissociatu ,medicine.symptom ,business ,Neuroscience ,Human - Abstract
PURPOSE OF REVIEW The aim is to review sleep disturbances in different movement disorders, mainly Parkinson's disease, and highlight current concepts on merging the boundaries between movement disorders and dissociative states of being. RECENT FINDINGS Since the observation that rapid eye movement sleep behavior disorder (RBD) may be an early marker of neurodegeneration, many studies focused on this disorder for the opportunity to explore the pathogenetic mechanisms underlying movement disorder and future neuroprotective therapies. It is also increasingly evident that this disorder is a possible marker for incoming dementia and for a general worst prognosis. Mechanisms of excessive daytime sleepiness in Parkinson's disease are still to be clarified and, if the role of hypocretin neuron loss is still doubtful, attention is moving to the role of monoaminergic system disruption. The role of dopamine in circadian rhythm regulation is opening new scenarios, namely the disruption of clock genes expression. Finally, the close relationship between sleep and movement disorder is emerging also in primarly sleep disorders. SUMMARY Recent studies provided new insights into the links between sleep and movement disorder that may simplify the diagnostic process and shed light on the underlying pathophysiological mechanisms.
- Published
- 2013
38. Skin sympathetic fiber -synuclein deposits: A potential biomarker for pure autonomic failure
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Masen Abdel Jaber, Alex Incensi, Vincenzo Donadio, Pietro Cortelli, Agostino Baruzzi, Rocco Liguori, Maria Pia Giannoccaro, V. Donadio, A. Incensi, P. Cortelli, M. P. Giannoccaro, M. A. Jaber, A. Baruzzi, and R. Liguori
- Subjects
Male ,metabolism/pathology, Biological Marker ,Pathology ,medicine.medical_specialty ,analysis ,diagnosis, Skin ,Shy-Drager Syndrome ,Diagnosis, Differential ,Pathogenesis ,Adrenergic Fiber ,diagnosis, Shy-Drager Syndrome ,analysis, Diagnosi ,Pure Autonomic Failure ,medicine ,Humans ,Pure autonomic failure ,Skin ,medicine.diagnostic_test ,business.industry ,Microneurography ,Middle Aged ,innervation/pathology, alpha-Synuclein ,medicine.disease ,Immunohistochemistry ,Peripheral ,Differential, Female, Humans, Immunohistochemistry, Male, Middle Aged, Pure Autonomic Failure ,Peripheral neuropathy ,Skin biopsy ,alpha-Synuclein ,Biomarker (medicine) ,Cholinergic ,Female ,Neurology (clinical) ,Adrenergic Fibers ,business ,Biomarkers - Abstract
Objective: This study aimed to test whether peripheral α-synuclein staining might be useful for pure autonomic failure (PAF) diagnosis, helping to differentiate degenerative from acquired peripheral autonomic neuropathy. Methods: We studied 21 patients with chronic peripheral autonomic neuropathy showing sympathetic and parasympathetic involvement as confirmed by cardiovascular reflexes and microneurography from the peroneal nerve. Twelve patients showed a specific cause of neuropathy (acquired autonomic neuropathy) whereas 9 had no specific acquired causes fulfilling the diagnostic criteria for PAF. Fifteen matched healthy subjects served as controls. Subjects underwent skin biopsy from thigh and leg to study skin innervation and phosphorylated α-synuclein deposits in the peripheral axons. Results: Somatic and autonomic skin innervations were significantly decreased in patients with peripheral autonomic neuropathy compared to controls. No differences were found between acquired autonomic neuropathy and PAF. The deposits of α-synuclein were not found in controls but served to distinguish acquired from degenerative autonomic peripheral neuropathy: all patients with PAF showed α-synuclein deposits, which were absent in patients with acquired autonomic neuropathy. Colocalization study disclosed α-synuclein neuritic inclusions in the postganglionic sympathetic adrenergic and cholinergic nerve fibers. Conclusions: Our study demonstrated that a search for neuritic inclusions of phosphorylated α-synuclein in the skin sympathetic nerve fibers could provide a sensitive in vivo biomarker for degenerative peripheral autonomic neuropathy and may shed more light on the pathogenesis of PAF.
- Published
- 2013
39. Peripheral Autonomic Neuropathy: Diagnostic Contribution of Skin Biopsy
- Author
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Alex Incensi, Maria Pia Giannoccaro, Vincenzo Donadio, Agostino Baruzzi, Rocco Liguori, Masen Abdel Jaber, Vitantonio Di Stasi, Pietro Cortelli, Fabio Pizza, Donadio V., Incensi A., Giannoccaro M.P., Cortelli P., Di Stasi V., Pizza F., Jaber M.A., Baruzzi A., and Liguori R.
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Autonomic system ,Biopsy ,Sympathetic nerve ,Thigh ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Sympathetic Fibers, Postganglionic ,DIAGNOSTIC TEST ,Peripheral nerve ,medicine ,Humans ,peripheral autonomic neuropathy ,Aged ,Nerve Fibers, Unmyelinated ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,General Medicine ,Middle Aged ,Peripheral ,Autonomic nervous system ,medicine.anatomical_structure ,Autonomic Nervous System Diseases ,Neurology ,Skin biopsy ,Female ,Neurology (clinical) ,Epidermis ,business ,Autonomic neuropathy - Abstract
Skin biopsy has gained widespread use for the diagnosis of somatic small-fiber neuropathy, but it also provides information on sympathetic fiber morphology. We aimed to ascertain the diagnostic accuracy of skin biopsy in disclosing sympathetic nerve abnormalities in patients with autonomic neuropathy. Peripheral nerve fiber autonomic involvement was confirmed by routine autonomic laboratory test abnormalities. Punch skin biopsies were taken from the thigh and lower leg of 28 patients with various types of autonomic neuropathy for quantitative evaluation of skin autonomic innervation. Results were compared with scores obtained from 32 age-matched healthy controls and 25 patients with somatic neuropathy. The autonomic cutoff score was calculated using the receiver operating characteristic curve analysis. Skin biopsy disclosed a significant autonomic innervation decrease in autonomic neuropathy patients versus controls and somatic neuropathy patients. Autonomic innervation density was abnormal in 96% of patients in the lower leg and in 79% of patients in the thigh. The abnormal findings disclosed by routine autonomic tests ranged from 48% to 82%. These data indicate the high sensitivity and specificity of skin biopsy in detecting sympathetic abnormalities; this method should be useful for the diagnosis of autonomic neuropathy, together with currently available routine autonomic testing.
- Published
- 2012
40. Muscle sympathetic response to arousal predicts neurovascular reactivity during mental stress
- Author
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Tomas Karlsson, Mikael Elam, Vincenzo Donadio, Rocco Liguori, Federica Giambattistelli, Göran Pegenius, Maria Pia Giannoccaro, and B. G. Wallin
- Subjects
medicine.medical_specialty ,Physiology ,Diastole ,Sympathetic nerve activity ,Sensory system ,Stimulus (physiology) ,Neurovascular bundle ,Developmental psychology ,Arousal ,Blood pressure ,Internal medicine ,Mental stress ,medicine ,Cardiology ,Psychology - Abstract
Mental stress often begins with a sudden sensory (or internal) stimulus causing a brief arousal reaction, and is followed by a more long lasting stress phase. Both arousal and stress regularly induce blood pressure (BP) increases whereas effects on muscle sympathetic nerve activity (MSNA) are variable. Here we have compared responses of MSNA and BP during arousal induced by an electrical skin stimulus and mental stress evoked by a 3 min paced auditory serial arithmetic test (PASAT) in 30 healthy males aged 33 ± 10 years. In addition, recordings were made of ECG, respiratory movements, electrodermal activity and perceived stress. We also monitored corresponding effects of a cold test (CT: 2 min immersion of a hand in ice water). The arousal stimulus evoked significant inhibition of one or two MSNA bursts in 16 subjects, who were classified as responders; the remaining 14 subjects were non-responders. During mental stress responders showed a significant decrease of MSNA and a lesser BP increase compared to non-responders. In non-responders MSNA was unchanged or increased. Perceived stress was higher in non-responders (P = 0.056), but other measures were similar in the two groups. In non-responders mental stress and the cold test induced increases of BP that lasted throughout the subsequent rest period. During the cold test MSNA and BP increased equally in responders and non-responders. In the whole group of subjects, there was a significant correlation (r = 0.80, P 0.6). Additionally arousal-induced MSNA change was positively correlated with blood pressure changes during MS (systolic BP: r = 0.48; P < 0.01; diastolic BP: r = 0.42; P < 0.05) but not with blood pressure changes during CT. We conclude that in males the MSNA response to arousal predicts the MSNA and BP responses to mental stress.
- Published
- 2012
41. Loss of temporal retinal nerve fibers in Parkinson disease: a mitochondrial pattern?
- Author
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Giovanna Calandra-Buonaura, Pietro Cortelli, Piero Barboni, Sara Bonazza, Giovanni Rizzo, Rocco Liguori, Giacomo Savini, Michele Carbonelli, Agostino Baruzzi, C. La Morgia, Maria Pia Giannoccaro, Paolo Martinelli, Cesa Scaglione, Sabina Capellari, and Valerio Carelli
- Subjects
Retina ,medicine.medical_specialty ,Parkinson's disease ,genetic structures ,medicine.diagnostic_test ,business.industry ,Mitochondrial disease ,Nerve fiber layer ,Retinal ,Anatomy ,medicine.disease ,eye diseases ,chemistry.chemical_compound ,medicine.anatomical_structure ,Neurology ,chemistry ,Optical coherence tomography ,Ophthalmology ,medicine ,Optic nerve ,sense organs ,Neurology (clinical) ,Mitochondrial optic neuropathies ,business - Abstract
Background and purpose: Optic nerve involvement is frequent in mitochondrial disease, and retinal abnormalities are described in Parkinson’s disease (PD). Methods: We evaluated retinal nerve fiber layer (RNFL) thickness by optical coherence tomography in 43 patients with PD and in 86 age-matched controls. We considered separately the eyes ipsilateral and contralateral to the most affected body side in patients with PD. ancova analysis, Pearson test, and multiple regression analysis were used (P
- Published
- 2012
42. Small nerve fiber involvement in patients referred for fibromyalgia
- Author
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Patrizia Avoni, Rocco Liguori, Vincenzo Donadio, Maria Pia Giannoccaro, and Alex Incensi
- Subjects
Cholinergic Fibers ,medicine.diagnostic_test ,Physiology ,business.industry ,Adrenergic ,Neurological examination ,Nerve fiber ,Thigh ,medicine.disease ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Physiology (medical) ,Anesthesia ,Fibromyalgia ,Neuropathic pain ,Skin biopsy ,medicine ,Neurology (clinical) ,business - Abstract
Introduction: Fibromyalgia (FM) is a chronic syndrome characterized by widespread pain often accompanied by other symptoms suggestive of neuropathic pain. We evaluated patients for small fiber neuropathy (SFN) who were referred for fibromyalgia (FM). Methods: We studied 20 consecutive subjects with primary FM. Patients underwent neurological examination, nerve conduction studies, and skin biopsies from distal leg and thigh. Results: Electrodiagnostic studies were normal in all patients. SFN was diagnosed in 6 patients by reduced epidermal nerve fiber density. These patients also showed abnormalities of both adrenergic and cholinergic fibers. Conclusions: A subset of FM subjects have SFN, which may contribute to their sensory and autonomic symptoms. Skin biopsy should be considered in the diagnostic work-up of FM. Muscle Nerve 49: 757–759, 2014
- Published
- 2014
43. Skin biopsy and I-123 MIBG scintigraphy findings in idiopathic Parkinson's disease and parkinsonism: A comparative study
- Author
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Maria Pia, Giannoccaro, Vincenzo, Donadio, Alex, Incensi, Fabio, Pizza, Ernesto, Cason, Vitantonio, Di Stasi, Paolo, Martinelli, Cesa, Scaglione, Sabina, Capellari, Giorgio, Treglia, Rocco, Liguori, Giannoccaro, M.P., Donadio, V., Incensi, A., Pizza, F., Cason, E., Di Stasi, V., Martinelli, P., Scaglione, C., Capellari, S., Treglia, G., and Liguori, R.
- Subjects
Male ,integumentary system ,small fiber neuropathy ,Biopsy ,Parkinson's disease ,Myocardial Perfusion Imaging ,Parkinson Disease ,Middle Aged ,Parkinsonism ,bacterial infections and mycoses ,Iodine Radioisotopes ,Autonomic Nervous System Diseases ,Parkinsonian Disorders ,Humans ,123I-MIBG scintigraphy ,Female ,skin biopsy ,Aged ,Skin - Abstract
(123) I-meta-iodobenzylguanidine ((123) I-MIBG) myocardial scintigraphy is considered reliable in differentiating idiopathic Parkinson's disease (IPD) from other parkinsonisms, but it is biased by pharmacological treatments. Skin biopsy is not influenced by therapy and has disclosed skin denervation in IPD. Our aims were to compare (123) I-MIBG scintigraphy and skin biopsy findings in IPD and parkinsonisms to (1) verify whether myocardial and skin denervations are linked; (2) explore the simultaneous extent of the autonomic dysfunction.We studied 22 IPD and 11 parkinsonism patients by means of (123) I-MIBG scintigraphy and skin biopsies.In the IPD group, both (123) I-MIBG scintigraphy and skin biopsy results were abnormal in 91% of patients, showing concordance in 82% of cases. In parkinsonisms, results of both tests were normal in all patients.(1) Skin biopsy and (123) I-MIBG scintigraphy provide comparable results; (2) in IPD, autonomic dysfunctions are often simultaneously widespread at cardiac and skin branches. © 2015 International Parkinson and Movement Disorder Society.
- Published
- 2015
44. Acute rhabdomyolysis induced by tonic–clonic epileptic seizures in a patient with glucose-6-phosphate dehydrogenase deficiency
- Author
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Rocco Liguori, Patrizia Riguzzi, Elena Pasini, Giacomo P. Comi, Valerio Carelli, Nereo Bresolin, Roberto Michelucci, Maria Lucia Valentino, Maria Pia Giannoccaro, R. Liguori, M. P. Giannoccaro, E. Pasini, P. Riguzzi, M. L. Valentino, G. P. Comi, V. Carelli, N. Bresolin, and R. Michelucci
- Subjects
medicine.medical_specialty ,business.industry ,seizure ,Status epilepticus ,medicine.disease ,rhabdomyolysi ,Tonic (physiology) ,Epilepsy ,chemistry.chemical_compound ,Endocrinology ,Neurology ,chemistry ,Internal medicine ,medicine ,epilepsy ,Neurology (clinical) ,medicine.symptom ,business ,Rhabdomyolysis ,Acute rhabdomyolysis ,Glucosephosphate Dehydrogenase Deficiency ,Nicotinamide adenine dinucleotide phosphate ,Glucose-6-phosphate dehydrogenase deficiency - Abstract
N.A.
- Published
- 2013
45. 93. Phosphorylated α-synuclein biomarker in skin nerves is differently expressed in pure autonomic failure and idiopathic Parkinson disease
- Author
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C. Piccinini, Maria Pia Giannoccaro, Pietro Cortelli, Vincenzo Donadio, Alex Incensi, Rocco Liguori, and A. Baruzzi
- Subjects
Denervation ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,animal diseases ,Disease ,bacterial infections and mycoses ,medicine.disease ,Sensory Systems ,nervous system diseases ,Pathogenesis ,nervous system ,Neurology ,In vivo ,Physiology (medical) ,Skin biopsy ,Phosphorylated α synuclein ,medicine ,Biomarker (medicine) ,heterocyclic compounds ,Neurology (clinical) ,business ,Pure autonomic failure - Abstract
The aim of this study was to characterize the expression in skin nerves of native (n-syn) and misfolded or phosphorylated (p-syn) α-synucleins in pure autonomic failure (PAF) and idiopathic Parkinson disease (IPD). We studied 30 patients, including 16 well-characterized IPD, 14 patients fulfilling PAF diagnostic criteria, and 15 age-matched controls. Subjects underwent skin biopsy from cervical, thigh and leg sites to study small nerve fibers and intraneural n-syn and p-syn. PAF and IPD both showed a skin denervation, more severely expressed in patients with higher p-syn load. N-syn was similarly expressed in both groups of patients and controls. By contrast, p-syn was not found in controls, but it was disclosed in all PAF and IPD patients with different skin innervation. In addition, abnormal α-syn deposits were found in all analysed skin samples in PAF, but in 49% of samples only with higher positivity rate in the cervical site in IPD. In conclusion: (1) intraneural p-syn was a reliable in vivo marker of PAF and IPD; (2) neuritic p-syn inclusions differed in PAF and IPD, suggesting a different underlying pathogenesis; (3) searching for abnormal p-syn deposits in skin nerves, the site of analysis is irrelevant in PAF, but it is critical in IPD.
- Published
- 2016
46. Somatic and autonomic small fiber neuropathy induced by bortezomib therapy: an immunofluorescence study
- Author
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Vitantonio Di Stasi, Walter Borsini, Vincenzo Donadio, Maria Pia Giannoccaro, Carolina Gomis Pèrez, Rocco Liguori, Giannoccaro M.P., Donadio V., Gomis Pèrez C., Borsini W., Di Stasi V., and Liguori R.
- Subjects
medicine.medical_specialty ,Sensory axonal neuropathy ,Neurology ,Ileus ,Urinary system ,Dermatology ,Gastroenterology ,Bortezomib ,Autonomic neuropathy ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,Skin biopsy ,medicine ,Multiple myeloma ,medicine.diagnostic_test ,business.industry ,General Medicine ,medicine.disease ,Surgery ,Psychiatry and Mental health ,Neurology (clinical) ,Small fiber neuropathy ,business ,medicine.drug - Abstract
Bortezomib is a new chemotherapeutic agent approved for the treatment of relapsed/refractory and newly diagnosed multiple myeloma. One of the major side effects of bortezomib is a peripheral length-dependent sensory axonal neuropathy and, less frequently, a small fiber neuropathy. Autonomic symptoms like postural dizziness, syncope, diarrhoea, ileus, impotence and urinary disturbances have been reported, nevertheless, autonomic neuropathy has never been characterized. We describe by means of immunofluorescence, the involvement of autonomic skin nerve fibers in three patients with small fiber neuropathy induced by bortezomib treatment.
- Published
- 2011
47. Impairment of brain and muscle energy metabolism detected by magnetic resonance spectroscopy in hereditary spastic paraparesis type 28 patients with DDHD1 mutations
- Author
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Maria Teresa Bassi, Rocco Liguori, Andrea Citterio, Maria Pia Giannoccaro, Alessia Arnoldi, Caterina Tonon, Raffaele Lodi, Nereo Bresolin, R. Liguori, M. P. Giannoccaro, A. Arnoldi, A. Citterio, C. Tonon, R. Lodi, N. Bresolin, and M. T. Bassi
- Subjects
In vivo magnetic resonance spectroscopy ,Male ,medicine.medical_specialty ,Pathology ,Heterozygote ,Neurology ,Magnetic Resonance Spectroscopy ,Adolescent ,Hereditary spastic paraplegia ,Biology ,medicine.disease_cause ,Pathogenesis ,Young Adult ,medicine ,Humans ,Genetic Predisposition to Disease ,Gene ,Paraplegia ,Mutation ,hereditary spastic paraparesis ,Muscles ,Skeletal muscle ,Brain ,Heterozygote advantage ,medicine.disease ,Pedigree ,medicine.anatomical_structure ,Phospholipases ,Neurology (clinical) ,Energy Metabolism - Abstract
Mutations in DDHD1 gene have been associated with the SPG28 subtype of Hereditary Spastic Paraparesis (HSP). Clinical phenotype includes axonal neuropathy, distal sensory loss, and cerebellar eye movement disturbances. We screened 96 index subjects from recessive HSP families for mutation and identified one family with two sibs carrying mutations in DDHD1 gene. Clinical, neuropsychological, and neuroimaging studies were performed, including MR spectroscopy of brain and muscle of the two mutated patients. Two novel heterozygous mutations in DDHD1 were found in the affected members of one family, with clinical features overlapping the SPG28 subtype. Of note, MR spectroscopy of brain and muscle in these patients indicated a mild deficit of brain energy metabolism in the oldest and most severely affected patient, while an impairment of energy metabolism was found in the skeletal muscle of both patients. Unlike the DDHD2 mutated patients, no evidence of lipid accumulation in the brain was found. Our data along with those previously reported suggest a dysfunction in the OXPHOS system possibly due to mitochondrial lipid content modification, which could be a central mechanism in the pathogenesis of SPG28.
- Published
- 2014
48. Skin nerve α-synuclein deposits: a biomarker for idiopathic Parkinson disease
- Author
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Sabina Capellari, Vincenzo Donadio, Rocco Liguori, V. Leta, Agostino Baruzzi, Cesa Scaglione, Alex Incensi, Patrizia Avoni, Paolo Martinelli, Maria Pia Giannoccaro, V. Donadio, A. Incensi, V. Leta, M. P. Giannoccaro, C. Scaglione, P. Martinelli, S. Capellari, P. Avoni, A. Baruzzi, and R. Liguori
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Pathology ,medicine.medical_specialty ,Parkin ,Pathogenesis ,metabolism/pathology, Parkinson Disease ,medicine ,Denervation ,Aged, Aged ,metabolism, Humans, Middle Aged, Nerve Fiber ,medicine.diagnostic_test ,business.industry ,innervation/metabolism/pathology, alpha-Synuclein ,Parkinsonism ,medicine.disease ,bacterial infections and mycoses ,Peripheral ,nervous system diseases ,80 and over, Biological Marker ,diagnosis/etiology/metabolism/pathology, Phosphorylation, Skin ,Peripheral neuropathy ,Skin biopsy ,complications/diagnosis/metabolism/pathology, Peripheral Nervous System Disease ,Biomarker (medicine) ,Neurology (clinical) ,business ,metabolism - Abstract
Objective: To investigate (1) whether phosphorylated α-synuclein deposits in skin nerve fibers might represent a useful biomarker for idiopathic Parkinson disease (IPD), and (2) the underlying pathogenesis of peripheral neuropathy associated with IPD. Methods: Twenty-one well-characterized patients with IPD were studied together with 20 patients with parkinsonisms assumed not to have α-synuclein deposits (PAR; 10 patients fulfilling clinical criteria for vascular parkinsonism, 6 for tauopathies, and 4 with parkin mutations) and 30 controls. Subjects underwent nerve conduction velocities from the leg to evaluate large nerve fibers and skin biopsy from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small nerve fibers and deposits of phosphorylated α-synuclein considered the pathologic form of α-synuclein. Results: Patients with IPD showed a small nerve fiber neuropathy prevalent in the leg with preserved large nerve fibers. PAR patients showed normal large and small nerve fibers. Phosphorylated α-synuclein was not found in any skin sample in PAR patients and controls, but it was found in all patients with IPD in the cervical skin site. Abnormal deposits were correlated with leg epidermal denervation. Conclusions: The search for phosphorylated α-synuclein in proximal peripheral nerves is a sensitive biomarker for IPD diagnosis, helping to differentiate IPD from other parkinsonisms. Neuritic inclusions of α-synuclein were correlated with a small-fiber neuropathy, suggesting their direct role in peripheral nerve fiber damage. Classification of evidence: This study provides Class III evidence that the presence of phosphorylated α-synuclein in skin nerve fibers on skin biopsy accurately distinguishes IPD from other forms of parkinsonism.
- Published
- 2014
49. Atypical late-onset hereditary spastic paraplegia with thin corpus callosum due to novel compound heterozygous mutations in the SPG11 gene
- Author
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Alessia Arnoldi, Rocco Liguori, Vincenzo Donadio, Maria Teresa Bassi, Patrizia Avoni, Maria Pia Giannoccaro, M. P. Giannoccaro, R. Liguori, A. Arnoldi, V. Donadio, P. Avoni, and M. T. Bassi
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Genetics ,Mutation ,Splice site mutation ,Hereditary spastic paraplegia ,business.industry ,HEREDITARY SPASTIC PARAPLEGIA ,medicine.disease ,medicine.disease_cause ,Compound heterozygosity ,Exon ,Neurology ,medicine ,SPG11 gene ,Missense mutation ,splice ,Neurology (clinical) ,Allele ,business - Abstract
Autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a heterogeneous group of complicated HSP with intellectual disability, among which SPG11 represents the most frequent subtype [1]. Disease onset occurs mainly during infancy/adolescence and is usually characterized by progressive spasticity and mental retardation and/or progressive cognitive decline [1]. Here, we describe an atypical phenotype of HSP-TCC related to new compound heterozygous mutations in the Spatacsin (SPG11) gene. The non-consanguineous family under examination has two affected brothers (Fig. 1). Patient II-3 is a 47-year-old male who developed walking difficulties and urinary disturbances at age 42 years. A brain MRI was considered as normal. His affected 53-years-old brother (II-1) developed spastic paraplegia at age 49 associated with urinary urgency and modifications in mood and character. His detailed evaluation was not performed as he refused to undergo to further investigations. Neurologic examination of patient II-3 showed nystagmus, lower limbs spasticity with brisk tendon reflexes and Babinski sign. Mini-mental state examination score was 26/30. The evaluation of the previous brain MRI revealed TCC and periventricular frontal hyperintensity on axial FLAIR images, termed ‘‘ears of the lynx sign’’ [2] (Fig. 1). Based on family history and MRI findings, we searched for mutations in SPG11 (by direct sequencing of all coding exons) after obtaining informed consent from the patient and his family (Ethics Committees of the two Institutions approved the study). Genetic analysis showed compound heterozygosity for a splice site mutation c.1891?1 G[T in intron 9 and a missense mutation c.7000G[C/p.A2334P in exon 39 of the SPG11 gene. The splice mutation is of paternal origin, while the missense change was transmitted by the mother. The analysis by RT-PCR and sequencing of the full-length SPG11 transcript from patient’s cells demonstrated that the splice site mutation leads to skipping of exon 9. The resulting in-frame deletion of 156 bp (c.1736_1891del156) leads to a putative protein-lacking 52 residues and carrying an amino acid change at the deletion junction (p.N579_E631[K). No other splicing alteration was observed, not even in the region encompassing the missense mutation, thereby excluding any possible effect of the missense mutation c.7000G[C on splicing. A deleterious effect on the processing of the SPG11 transcript was instead demonstrated for another missense change c.2608A[G/p.Ile870ValfsX20, which leads to early protein truncation [3]. In summary, the compound heterozygous mutations in this patient lead to the expression of a putative protein lacking only 52 residues from one allele and to a protein carrying a missense change from the other. The Ala2334 residue is quite conserved through evolution, and different softwares (see Fig. 1 legend) predict damaging/deleterious effects deriving from the missense change. The absence of any recognizable domain in the deleted portion of the protein along with the lack of definite functional data on M. P. Giannoccaro R. Liguori P. Avoni Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
- Published
- 2014
50. Sympathetic and cardiovascular changes during sleep in narcolepsy with cataplexy patients
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V. Leta, Giuseppe Plazzi, Vincenzo Donadio, Rocco Liguori, Stefano Vandi, Fabio Pizza, Maria Pia Giannoccaro, V. Donadio, R. Liguori, S. Vandi, M. P. Giannoccaro, F. Pizza, V. Leta, and G. Plazzi
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Adult ,Male ,medicine.medical_specialty ,Sympathetic Nervous System ,Polysomnography ,physiopathology, Young Adult ,Sleep, REM ,Sleep spindle ,Blood Pressure ,Non-rapid eye movement sleep ,Cardiovascular System ,physiology, Humans, Male, Middle Aged, Narcolepsy ,Young Adult ,Adult, Blood Pressure ,Heart Rate ,physiology, Sleep ,Internal medicine ,physiology, Cardiovascular System ,physiopathology, Case-Control Studies, Female, Heart Rate ,mental disorders ,medicine ,Humans ,Neuroscience of sleep ,Slow-wave sleep ,Narcolepsy ,Sleep Stages ,General Medicine ,Middle Aged ,medicine.disease ,Sleep in non-human animals ,physiopathology, Polysomnography, Sleep ,Endocrinology ,physiology, Sympathetic Nervous System ,Case-Control Studies ,REM ,physiology ,Female ,physiopathology ,Psychology ,K-complex ,Sleep ,psychological phenomena and processes - Abstract
Objective Neural mechanisms underlying sleep-onset rapid eye movement (REM) periods (SOREMPs) in narcolepsy and the role of hypocretin in driving sympathetic changes during sleep are misunderstood. We aimed to characterize autonomic changes during sleep in narcolepsy with cataplexy (NC) patients to clarify the nature of SOREMP events and the effect of hypocretin deficiency on sympathetic activity during sleep. Methods We observed 13 hypocretin-deficient NC patients and five healthy controls who underwent nocturnal video-polysomnography (v-PSG) with blood pressure (BP) recording, heart rate (HR), skin sympathetic activity (SSA), and muscle sympathetic nerve activity (MSNA) from the peroneal nerve by microneurography. Results Compared to wake, control participants displayed a progressive significant decrease of BP and sympathetic activities during nonrapid eye movement (NREM) sleep and an increase of autonomic activity during REM sleep, as expected. NC patients showed: (1) a decrease of sympathetic activities during SOREMP comparable to NREM sleep stage 1 (N1) but in contrast to the increased activity typical of REM sleep; and (2) physiologic sympathetic change during the following sleep stages with a progressive decrease during NREM sleep stage 2 (N2) and NREM sleep stage 3 (N3) and a clear increase in REM sleep, though BP did not show the physiologic decrease during sleep (nondipper pattern). Conclusions SOREMPs in NC patients lack the sympathetic activation occurring during physiologic REM sleep, thus suggesting a dissociated REM sleep condition. In addition, our data indicated that hypocretin plays a limited role in the regulation of sympathetic changes during sleep.
- Published
- 2014
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