Publications by authors named "Enrico Marchioni"

77 Publications

Characterization and management of neurological adverse events during immune-checkpoint inhibitors treatment: an Italian multicentric experience.

Neurol Sci 2021 Aug 23. Epub 2021 Aug 23.

"C. Mondino" National Neurological Institute, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy.

Background: Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase of ICI oncological indications, their incidence is growing. Their recognition and management remain nevertheless challenging.

Methods: A national, web-based database was built to collect cases of neurological symptoms in patients receiving ICI and not attributable to other causes after an adequate workup.

Results: We identified 27 patients who developed nirAEs (20 males, median age 69 years). Patients received anti-PD1/PDL1 (78%), anti-CTLA4 (4%), or both (19%). Most common cancers were melanoma (30%) and non-small cell lung cancer (26%). Peripheral nervous system was mostly affected (78%). Median time to onset was 43.5 days and was shorter for peripheral versus central nervous system toxicities (36 versus 144.5 days, p = 0.045). Common manifestations were myositis (33%), inflammatory polyradiculoneuropathies (33%), and myasthenia gravis (19%), alone or in combination, but the spectrum of diagnoses was broad. Most patients received first-line glucocorticoids (85%) or IVIg (15%). Seven patients (26%) needed second-line treatments. At last follow-up, four (15%) patients were deceased (encephalitis, 1; myositis/myasthenia with concomitant myocarditis, 2; acute polyradiculoneuropathy, 1), while seven (26%) had a complete remission, eight (30%) partial improvement, and six (22%) stable/progressing symptoms. ICI treatment was discontinued in most patients (78%).

Conclusions: Neurological irAEs are rare but potentially fatal. They primarily affect neuromuscular structures but encompass a broad range of presentations. A prompt recognition is mandatory to timely withheld immunotherapy and administrate glucocorticoids. In corticoresistant or severely affected patients, second-line treatments with IVIg or plasmapheresis may result in additional benefit.
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http://dx.doi.org/10.1007/s10072-021-05561-zDOI Listing
August 2021

Acute myelitis and ChAdOx1 nCoV-19 vaccine: Casual or causal association?

J Neuroimmunol 2021 10 31;359:577686. Epub 2021 Jul 31.

Neuroncology and Neuroinflammation Unit, IRCCS Mondino Foundation, Pavia, Italy. Electronic address:

A 44-year-old previously healthy woman developed acute myelitis in close temporal relationship with ChAdOx1 nCoV-19 vaccine first-dose administration. The neurological involvement was mainly sensory with neuroimaging showing two mono-metameric lesions involving the posterior and lateral cord at dorsal level. Significant improvement was promptly recorded with high-dose intravenous steroids, with complete recovery within one month. The strict temporal relationship between vaccination and myelitis, together with the absence of clues pointing to alternative diagnoses, might suggest a conceivable role for anti-SARS-CoV-2 vaccine as immunological trigger, although a causal relationship has yet to be established and our preliminary observation suggests caution.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325554PMC
October 2021

COVID-19 in patients with myasthenia gravis: Epidemiology and disease course.

Muscle Nerve 2021 08 12;64(2):206-211. Epub 2021 Jun 12.

Neuroncology Unit, IRCCS Mondino Foundation, Pavia, Italy.

Introduction/aims: Coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global pandemic. Patients with myasthenia gravis (MG), often treated with immunosuppressants, might be at higher risk of developing COVID-19 and of demonstrating a severe disease course. We aimed to study prevalence and describe features of COVID-19 in MG patients.

Methods: In May 2020, we conducted telephonic interviews with MG patients followed at our referral center. We collected structured data regarding MG and COVID-19, which was diagnosed as probable or confirmed according to the European Centre for Disease Prevention and Control case definition. We compared confirmed-COVID-19 prevalence calculated from the beginning of the pandemic in MG patients with that of the overall Pavia district.

Results: We interviewed 162 MG patients (median age, 66 y; interquartile range 41-77; males 59.9%), 88 from the Pavia district. Three patients had SARS-CoV-2-confirmed by polymerase chain reaction and eight had probable-COVID-19. In the Pavia district, the prevalence of confirmed-COVID-19 among MG patients (1/88, 1.14%) and overall population (4777/546 515, 0.87%) did not differ (P = .538). Higher Myasthenia Gravis Foundation of America clinicalclass and the need for recent rescue treatment, but not ongoing immunosuppressive treatments, were associated with COVID-19 risk. Of 11 MG patients with probable/confirmed-COVID-19, 3 required ventilator support, and 2 elderly patients died of COVID-19 respiratory insufficiency. Only 1 of11 patients experienced worsening MG symptoms, which improved after increasing their steroid dose.

Discussion: The risk of COVID-19 in MG patients seems to be no higher than that of the general population, regardless of immunosuppressive therapies. In our cohort, COVID-19 barely affected MG course.
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http://dx.doi.org/10.1002/mus.27324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242475PMC
August 2021

RFC1 expansions are a common cause of idiopathic sensory neuropathy.

Brain 2021 06;144(5):1542-1550

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren's syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies.
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http://dx.doi.org/10.1093/brain/awab072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262986PMC
June 2021

Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts.

Neurol Neuroimmunol Neuroinflamm 2021 03 12;8(2). Epub 2021 Jan 12.

From the Neuroncology Unit (G.B., E.V., E.M.), and Neuroradiology Unit (M.P., A.P.), IRCCS Mondino Foundation, Pavia; Molecular Virology Unit (G.C., F.B.), Microbiology and Virology Department, Diagnostic Radiology, Interventional Radiology and Neuroradiology Unit (A.M.S.), Bone Marrow Transplantation Unit (A.A.C., P.B., O.B.), Infectious and Tropical Diseases Unit (A.D.M.), Pediatric Clinic (V.R., T.F., S.S.), and Pediatric Hematology/Oncology (F.C., M.Z.), Fondazione IRCCS Policlinico San Matteo, Pavia; and Department of Brain and Behavioral Sciences (A.P.), Department of Molecular Medicine (P.B., O.B.), and Department of Clinical, Surgical, Diagnostic and Paediatric Sciences (F.B.), University of Pavia, Italy.

Objective: The aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing.

Methods: We performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompetent and immunocompromised hosts.

Results: Of the 926 patients tested for HHV-6 during the period of interest, 45 met the study criteria. Among immunocompetent hosts (n = 17), HHV-6 encephalitis was diagnosed to 4 infants or children presenting with seizures or mild encephalopathy during primary HHV-6 infection (CSF/blood replication ratio <<1 in all cases). Among immunocompromised hosts (n = 28), HHV-6 encephalitis was diagnosed to 7 adolescents/adults with hematologic conditions presenting with altered mental status (7/7), seizures (3/7), vigilance impairment (3/7), behavioral changes (2/7), hyponatremia (2/7), and anterograde amnesia (1/7). Initial brain MRI was altered only in 2 patients, but 6 of the 7 had a CSF/blood replication ratio >1.

Conclusions: The detection of a CSF/blood replication ratio >1 represented a specific feature of immunocompromised patients with HHV-6 encephalitis and could be of special help to establish a diagnosis of HHV-6 encephalitis in hematopoietic stem cell transplant recipients lacking radiologic evidence of limbic involvement.
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http://dx.doi.org/10.1212/NXI.0000000000000942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963435PMC
March 2021

Adoptive Transfer of JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy.

Ann Neurol 2021 04 10;89(4):769-779. Epub 2021 Feb 10.

Cell Factory, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.

Objective: Progressive multifocal leukoencephalopathy (PML) is still burdened by high mortality in a subset of patients, such as those affected by hematological malignancies. The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV)-specific T cell therapy in a cohort of hematological patients with PML.

Methods: Between 2014 and 2019, 9 patients with a diagnosis of "definite PML" according to the 2013 consensus who were showing progressive clinical deterioration received JCPyV-specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen-derived peptides.

Results: None of the patients experienced treatment-related adverse events. In the evaluable patients, an increase in the frequency of circulating JCPyV-specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up.

Interpretation: Among other novel treatments, T cell therapy is emerging as a viable treatment option in patients with PML, particularly for those not amenable to restoration of specific immunity. Neurologists should be encouraged to refer PML patients to specialized centers to allow access to this treatment strategy. ANN NEUROL 2021;89:769-779.
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http://dx.doi.org/10.1002/ana.26020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248385PMC
April 2021

Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions.

J Neurol Neurosurg Psychiatry 2021 07 6;92(7):751-756. Epub 2020 Nov 6.

Unit of Neurology, ASST Valcamonica, Esine (Bs), Italy.

Objective: Single cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19.

Methods: GBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered.

Results: Incidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002).

Conclusions: This study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture.
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http://dx.doi.org/10.1136/jnnp-2020-324837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650204PMC
July 2021

A Rare Syndrome Causing Neurogenic Dysphagia.

Dysphagia 2020 Nov 4. Epub 2020 Nov 4.

Clinical Neurophysiology Unit, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy.

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http://dx.doi.org/10.1007/s00455-020-10208-wDOI Listing
November 2020

Impact of multiple sclerosis risk loci in postinfectious neurological syndromes.

Mult Scler Relat Disord 2020 Sep 24;44:102326. Epub 2020 Jun 24.

Fondazione Istituto Neurologico Nazionale IRCCS Mondino, via Mondino 2, 27100 Pavia, Italy.

Background: The genetic component of multiple sclerosis (MS) is now set to 200 autosomal common variants. However, it is unclear how genetic knowledge be clinically used in the differential diagnosis between MS and other inflammatory conditions like adult-onset postinfectious neurological syndromes (PINS). The aim of this study was to investigate whether PINS and MS have a shared genetic background using an updated polygenic risk scores.

Methods: Eighty-eight PINS patients have been consecutively recruited between 1996 and 2016 at Mondino Foundation of Pavia, diagnosed according to clinical, MRI and CSF findings and followed-up for several years. Patients were typed using Illumina array, and genotypes imputed using the 1000 Genomes Project reference panel. A weighted genetic risk score (wGRS) has been calculated based on autosomal MS risk loci derived from large-scale studies, and an HLA genetic burden (HLAGB) was also calculated on loci associated to MS.

Results: PINS occurred as an episode of myelitis in 44% of patients, encephalomyelitis in 44%, and encephalitis in remaining cases, with an involvement of peripheral nervous system in 41% of patients. Mean age of onset was 50.1 years, and female:male ratio was 1.4. Patients were followed-up for a mean of 7.2 years, and at last visit 55% had a low disability grade (mRS 0-1). Disease was monophasic in 67% of patients, relapsing in 18% and chronic-progressive in 15%. The wGRS of PINS cases was comparable to 370 healthy controls, while significantly lower compared to 907 bout-onset MS (BOMS) cases (wGRS= 20.9 vs 21.2; p<0.0001). The difference was even larger for PINS with peripheral nervous system involvement (wGRS=20.6) vs BOMS.

Conclusion: The distinction between MS and PINS is not easy to make in clinical practice. However, our study shows that the new set of MS risk alleles does not confer increased susceptibility to PINS. These data support the importance to discriminate these cases from MS with pathophysiological and therapeutic implications.
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http://dx.doi.org/10.1016/j.msard.2020.102326DOI Listing
September 2020

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.

Nat Genet 2020 05 4;52(5):473-481. Epub 2020 May 4.

Istituiti Clinici Scientifici Maugeri IRCCS, Environmental Research Center, Pavia, Italy.

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes.
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http://dx.doi.org/10.1038/s41588-020-0615-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353599PMC
May 2020

Cranial nerve palsies in patients with hematological malignancies: a case series.

Int J Neurosci 2020 Aug 7;130(8):777-780. Epub 2020 Jan 7.

IRCCS C. Mondino Foundation, Pavia, Italy.

Cranial neuropathies (CNs) can be due to a wide spectrum of causes, and the differential diagnosis is particularly challenging in patients with positive history of hematological malignancies, when neoplastic meningitis (NM) must be excluded. We retrospectively selected a series of twelve haematological patients with isolated cranial neuropathies (ICNs) or multiple cranial neuropathies (MCNs). among 71 patients that developed neurologic symptoms during different stages of the cancer, between 1 January, 2010 and 31 December, 2017. Brain and cauda equina magnetic resonance imaging (MRI) with gadolinium, cerebrospinal fluid (CSF) analysis, including flow cytometry for cell immunophenotyping and microbiological exams were performed in all patients. Patients developed signs and symptoms of involvement of isolated ( = 11) or multiple ( = 1) cranial nerves, at different stages of the primary disease, and, in 5 of these cases in complete remission after hematopoietic stem cell transplantation. Among the 5 cases that eventually were diagnosed as having NM, cerebrospinal fluid was positive for neoplastic cells in 3, and MRI gadolinium-enhancement was present in 3. The other episodes were attributed to heterogeneous pathologies that were unrelated to meningeal infiltration by neoplastic cells. Our observations confirm that NM in haematological malignancies can yield insidious isolated signs of cranial nerves. Only a multidisciplinary approach allows prompt recognition of these conditions through a challenging process of differential diagnosis, and proper therapies.
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http://dx.doi.org/10.1080/00207454.2019.1705810DOI Listing
August 2020

Diagnosing acute encephalitis in patients with hematological disorders: caveats and pitfalls.

J Neurovirol 2020 04 20;26(2):257-263. Epub 2019 Dec 20.

Neuroncology Unit, IRCCS Mondino Foundation, Pavia, Italy.

The aim of this study was to review the quality of the diagnostic work-up for acute encephalitis carried out at our center in a cohort of patients with hematological disorders. Our data showed substantial heterogeneity in investigating patients. Not all patients had their CSF tested for viruses commonly responsible for encephalitis in immunocompetent individuals (e.g., VZV, enterovirus). A blood sample for the calculation of the CSF/blood replication ratio was collected in 74% of cases. CSF cultures and immunophenotyping of CSF cells were performed in 77% and 21% of patients, respectively. A multidisciplinary consensus is needed to improve current guidelines and standardize diagnostic protocols.
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http://dx.doi.org/10.1007/s13365-019-00817-zDOI Listing
April 2020

Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype.

Neurol Neuroimmunol Neuroinflamm 2020 01 21;7(1). Epub 2019 Nov 21.

From the Department of Brain and Behavioral Sciences (A.C., I.C., G.C., R.C., E.V.), University of Pavia, Pavia, Italy; Department of Neuromuscular Disease (A.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Neuroalgology Unit (R.L., P.D., L.P., G.L.), IRCCS Fondazione Istituto Neurologico "Carlo Besta," Milan, Italy; Department of Neurosciences (C.B., M.R., A.S.), University of Padova, Padova, Italy; IRCCS Mondino Foundation (I.C., G.C., E.Z., R.C., M.G., E.V., E.A., A.B., D.F.), Pavia, Italy; Department of Neuroscience (L.B., C.D.M., A.S.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino (L.B., C.D.M., A.S.), Genova, Italy; Department of Neurosciences (F.M., E.S., A.T.), Odontostomatological and Reproductive Sciences, University of Naples "Federico II," Naples, Italy; Fondazione Policlinico Universitario Agostino Gemelli-IRCCS. UOC Neurologia (M.L., A.R., M.S.), Rome, Italy; Università Cattolica del Sacro Cuore (M.L., A.R., M.S.), Rome, Italy; Section of Neurology (S.F., S.M.), Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; Department of Neurology and Stroke Unit (A.M.C.), Ospedale di Circolo/Fondazione Macchi, Varese, Italy; Department of Systems Medicine (G.A.M., G.M.), University of Rome Tor Vergata, Rome, Italy; Neurological Department (A.R.), ASST Lecco; Ospedale Treviglio ASST Bergamo Ovest (M.C.), Italy; Department of Neurology (R.F., F.C.), San Raffaele Scientific Institute, Milan, Italy; Department of Neurorehabilitation Sciences (M.C.), Casa Cura Policlinico (CCP), Milan, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Messina, Messina, Italy; Department of Medicine, Surgery and Neurosciences (F.G.), University of Siena, Italy; Referral Center for Neuromuscular Diseases and ALS (L.K., E.M.), AP-HM, Timone University Hospital, Marseille, France; Université de Bordeaux (C.M.), Interdisciplinary Institute for Neuroscience, Bordeaux, France; Humanitas Clinical and Research Center (C.G., P.D., E.N.-O.), Milan University, Milan, Italy; IRCCS Centro Neurolesi "Bonino Pulejo" (C.S.), Messina, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco" (G.B., G.L.), University of Milan, Milan, Italy; and Institute for Neurosciences of Montpellier (J.D.), INSERM U1051, Montpellier University, Hopital Saint Eloi, Montpellier, France.

Objective: To assess the prevalence and isotypes of anti-nodal/paranodal antibodies to nodal/paranodal proteins in a large chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort, compare clinical features in seronegative vs seropositive patients, and gather evidence of their isotype-specific pathogenic role.

Methods: Antibodies to neurofascin-155 (Nfasc155), neurofascin-140/186 (Nfasc140/186), contactin-1 (CNTN1), and contactin-associated protein 1 (Caspr1) were detected with ELISA and/or cell-based assay. Antibody pathogenicity was tested by immunohistochemistry on skin biopsy, intraneural injection, and cell aggregation assay.

Results: Of 342 patients with CIDP, 19 (5.5%) had antibodies against Nfasc155 (n = 9), Nfasc140/186 and Nfasc155 (n = 1), CNTN1 (n = 3), and Caspr1 (n = 6). Antibodies were absent from healthy and disease controls, including neuropathies of different causes, and were mostly detected in patients with European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite CIDP (n = 18). Predominant antibody isotypes were immunoglobulin G (IgG)4 (n = 13), IgG3 (n = 2), IgG1 (n = 2), or undetectable (n = 2). IgG4 antibody-associated phenotypes included onset before 30 years, severe neuropathy, subacute onset, tremor, sensory ataxia, and poor response to intravenous immunoglobulin (IVIG). Immunosuppressive treatments, including rituximab, cyclophosphamide, and methotrexate, proved effective if started early in IVIG-resistant IgG4-seropositive cases. Five patients with an IgG1, IgG3, or undetectable isotype showed clinical features indistinguishable from seronegative patients, including good response to IVIG. IgG4 autoantibodies were associated with morphological changes at paranodes in patients' skin biopsies. We also provided preliminary evidence from a single patient about the pathogenicity of anti-Caspr1 IgG4, showing their ability to penetrate paranodal regions and disrupt the integrity of the Nfasc155/CNTN1/Caspr1 complex.

Conclusions: Our findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment.

Classification Of Evidence: This study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%).
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http://dx.doi.org/10.1212/NXI.0000000000000639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935837PMC
January 2020

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course.

J Clin Med 2019 Nov 18;8(11). Epub 2019 Nov 18.

Department of Rheumatology, S. Maria Hospital-IRCCS, 42123 Reggio Emilia, Italy.

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.
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http://dx.doi.org/10.3390/jcm8112013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912490PMC
November 2019

Brain MR findings in patients treated with particle therapy for skull base tumors.

Insights Imaging 2019 Sep 23;10(1):94. Epub 2019 Sep 23.

Diagnostic Imaging Unit, National Center of Oncological Hadrontherapy (CNAO), 27100, Pavia, Italy.

Nowadays, hadrontherapy is increasingly used for the treatment of various tumors, in particular of those resistant to conventional radiotherapy. Proton and carbon ions are characterized by physical and biological features that allow a high radiation dose to tumors, minimizing irradiation to adjacent normal tissues. For this reason, radioresistant tumors and tumors located near highly radiosensitive critical organs, such as skull base tumors, represent the best target for this kind of therapy. However, also hadrontherapy can be associated with radiation adverse effects, generally referred as acute, early-delayed and late-delayed. Among late-delayed effects, the most severe form of injury is radiation necrosis. There are various underlying mechanisms involved in the development of radiation necrosis, as well as different clinical presentations requiring specific treatments. In most cases, radiation necrosis presents as a single focal lesion, but it can be multifocal and involve a single or multiple lobes simulating brain metastasis, or it can also involve both cerebral hemispheres. In every case, radiation necrosis results always related to the extension of radiation delivery field. Multiple MRI techniques, including diffusion, perfusion imaging, and spectroscopy, are important tools for the radiologist to formulate the correct diagnosis. The aim of this paper is to illustrate the possible different radiologic patterns of radiation necrosis that can be observed in different MRI techniques in patients treated with hadrontherapy for tumors involving the skull base. The images of exemplary cases of radiation necrosis are also presented.
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http://dx.doi.org/10.1186/s13244-019-0784-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757093PMC
September 2019

Clinical, laboratory features, and prognostic factors in adult acute transverse myelitis: an Italian multicenter study.

Neurol Sci 2019 Jul 22;40(7):1383-1391. Epub 2019 Mar 22.

Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.

Objectives: We compared the clinical, laboratory, and radiological features of different subgroups of acute transverse myelitis (ATM) diagnosed according to the criteria established by the Transverse Myelitis Consortium Working Group (TMCWG) as well as of non-inflammatory acute transverse myelopathies (NIATM) to identify possible short- and long-term prognostic factors.

Methods: A multicenter and retrospective study comprising 110 patients with ATM and 15 NIATM admitted to five Italian neurological units between January 2010 and December 2014 was carried out.

Results: A significantly higher frequency of isolated sensory disturbances at onset in ATM than in NIATM patients (chi-square = 14. 7; P = 0.005) and a significantly higher frequency of motor symptoms in NIATM than ATM (chi-square = 12.4; P = 0.014) was found. ATM patients with high disability at discharge had more motor-sensory symptoms without (OR = 3.87; P = 0.04) and with sphincter dysfunction at onset (OR = 7.4; P = 0.0009) compared to those with low disability. Higher age (OR = 1.08; P = 0.001) and motor-sensory-sphincter involvement at onset (OR = 9.52; P = 0.002) were significantly associated with a high disability score at discharge and after a median 1-year follow-up.

Conclusions: The diagnosis of ATM may prevail respect to that of NIATM when a sensory symptomatology at onset occurs. In ATM, patients older and with motor-sensory involvement with or without sphincter impairment at admission could experience a major risk of poor prognosis both at discharge and at longer time requiring a timely and more appropriate treatment.
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http://dx.doi.org/10.1007/s10072-019-03830-6DOI Listing
July 2019

Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma.

J Neurooncol 2019 May 6;142(3):455-462. Epub 2019 Feb 6.

Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milan, Italy.

Background And Purpose: Glioblastoma (GBM) is the most aggressive and frequent subtype of all malignant gliomas. At the time of recurrence, therapeutic options are lacking. Ortataxel, a second-generation taxane was reported to be effective in pre-clinical and phase I clinical studies. The aim of this study was to evaluate a potential therapeutic activity of ortataxel in patients with GBM recurring after surgery and first line treatment.

Methods: In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75 mg/m i.v. every 3 weeks until disease progression. The primary objective of the study was to evaluate the activity of ortataxel in terms of progression free survival (PFS) at 6 months after the enrollment. PFS, overall survival at 9 months after the enrollment, objective response rate, compliance and safety were evaluated as secondary endpoints.

Results: Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6 months after the enrollment, observed in the first stage was four (11.4%), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2% of patients and leukopenia that occurred in 15.8% of patients.

Conclusion: Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time.

Trial Registration: This study is registered with ClinicalTrials.gov, number NCT01989884.
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http://dx.doi.org/10.1007/s11060-019-03116-zDOI Listing
May 2019

NMDAR encephalitis presenting as akinesia in a patient with Parkinson disease.

J Neuroimmunol 2019 03 12;328:35-37. Epub 2018 Dec 12.

Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy. Electronic address:

We describe the case of a woman with Parkinson disease who developed an N-methyl-d-aspartate receptor antibody-mediated encephalitis. As a novelty, the encephalitis presentation mimicked a worsening of the pre-existing extrapyramidal syndrome, manifesting mainly as severe bradykinesia and, eventually, akinesia. Brain MRI was normal, whereas cerebrospinal fluid (CSF) analysis disclosed unique-to-CSF oligoclonal bands. Prompt identification and timely immunotherapy led to a complete recovery.
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http://dx.doi.org/10.1016/j.jneuroim.2018.12.002DOI Listing
March 2019

Lower motor neuron syndrome in a patient with HER2-positive metastatic breast cancer: A case report and review of the literature.

Clin Neurol Neurosurg 2018 09 6;172:141-142. Epub 2018 Jul 6.

IRCCS "C. Mondino" Foundation, National Neurological Institute, Pavia, Italy.

Paraneoplastic neurological syndromes are very rare and often associated to breast, ovarian and small cells lung cancers. Paraneoplastic motor neuron diseases (MNDs) are even rarer, and frequently described in patients with breast cancer. We presented the first case of patient affected by HER2-positive breast tumor and possible paraneoplastic lower motor neuron disease. In literature, few cases are reported but no one highlights the tumor receptors' profile. Instead, HER2-positive breast cancers are prone to be related to anti-Yo-associated paraneoplastic cerebellar disorders. Anti-onconeural antibodies positivity can be rarely found, confirming that paraneoplastic MND have no specific biomarkers. The presence of CSF oligoclonal bands (OBs) suggests the presence of immune-mediated mechanism, in absence of other possible OBs causes.
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http://dx.doi.org/10.1016/j.clineuro.2018.06.038DOI Listing
September 2018

Efficacy of rituximab as third-line therapy in combined central and peripheral demyelination.

Neurol Clin Pract 2017 Dec;7(6):534-537

Department of Pediatrics (SS, TF), University of Pavia, IRCCS Policllinico S. Matteo Foundation; Neuroscience Consortium (EV), University of Pavia, Monza Policlinico and Pavia Mondino; Department of Neurology (EM, EV), C. Mondino National Neurological Institute; C. Mondino National Neurological Institute (AC, AL, AP, DF), Pavia, Italy; and Molecular Neuroscience (AC), University College London Institute of Neurology, UK.

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http://dx.doi.org/10.1212/CPJ.0000000000000388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800713PMC
December 2017

Bing-Neel Syndrome: Illustrative Cases and Comprehensive Review of the Literature.

Mediterr J Hematol Infect Dis 2017 18;9(1):e2017061. Epub 2017 Oct 18.

IRCCS, 'C. Mondino' National Neurological Institute, Pavia, Italy.

The Bing-Neel syndrome is a rare neurological complication of Waldenström's Macroglobulinemia which results from a direct involvement of central nervous system by malignant lymphoplasmacytic cells. The clinical suspicion of Bing-Neel syndrome may be overlooked because neurologic symptoms are heterogeneous, nonspecific and sometimes underhand. A definitive diagnosis of Bing-Neel syndrome can be confidently made using brain and spinal cord magnetic resonance imaging as well as histopathology and/or cerebrospinal fluid analysis to confirm the neoplastic infiltration of central nervous system. The detection in the cerebrospinal fluid of patients with Bing-Neel syndrome of the MYD88 (L265P) somatic mutation, which is highly recurrent in Waldenström's Macroglobulinemia, proved useful for the diagnosis and monitoring of central nervous system involvement. Despite recommendations recently published, there is still no clear consensus on treatment of Bing-Neel syndrome, which includes systemic immunochemotherapy, intrathecal chemotherapy and brain irradiation as possible options. Ibrutinib, a Bruton kinase inhibitor approved for Waldenström's Macroglobulinemia, has been recently added to the therapeutic armamentarium of Bing-Neel syndrome due to its ability to pass the blood-brain barrier. However, prospective clinical trials are eagerly awaited with the aim to define the optimal treatment strategy. Here we describe four illustrative cases of Bing-Neel syndrome diagnosed and treated at our Institution and review the literature on this topic.
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http://dx.doi.org/10.4084/MJHID.2017.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667529PMC
October 2017

Anti-NF155 chronic inflammatory demyelinating polyradiculoneuropathy strongly associates to HLA-DRB15.

J Neuroinflammation 2017 Nov 16;14(1):224. Epub 2017 Nov 16.

Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Mas Casanovas 90, 08041, Barcelona, Spain.

Background: The aim of the research is to study the human leukocyte antigen (HLA) class II allele frequencies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with anti-neurofascin 155 (NF155) antibodies.

Methods: Thirteen anti-NF155+ and 35 anti-NF155 negative (anti-NF155neg) CIDP patients were included in a case-control study. The frequencies of the DRB1 HLA allele were analyzed in all patients while DQ frequencies were only studied in patients sharing the DRB1*15 allele. In silico HLA-peptide binding and NF155 antigenicity, predictions were performed to analyze overlap between presented peptides and antigenic regions.

Results: DRB1*15 alleles (DRB1*15:01 and DRB1*15:02) were present in 10 out of 13 anti-NF155+ CIDP patients and in only 5 out of 35 anti-NF155neg CIDP patients (77 vs 14%; OR = 20, CI = 4.035 to 99.13). DRB1*15 alleles appeared also in significantly higher proportions in anti-NF155+ CIDP than in normal population (77 vs 17%; OR = 16.9, CI = 4.434 to 57.30). Seven anti-NF155+ CIDP patients (53%) and 5 anti-NF155neg CIDP patients had the DRB1*15:01 allele (OR = 7, p = 0.009), while 3 anti-NF155+ CIDP patients and none of the anti-NF155neg CIDP patients had the DRB1*15:02 allele (OR = 23.6, p = 0.016). In silico analysis of the NF155 peptides binding to DRB1*15 alleles showed significant overlap in the peptides presented by the 15:01 and 15:02 alleles, suggesting functional homology.

Conclusions: DRB1*15 alleles are the first strong risk factor associated to a CIDP subset, providing additional evidence that anti-NF155+ CIDP patients constitute a differentiated disease within the CIDP syndrome.
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http://dx.doi.org/10.1186/s12974-017-0996-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691853PMC
November 2017

Predictors of outcome in a large retrospective cohort of patients with transverse myelitis.

Mult Scler 2018 11 2;24(13):1743-1752. Epub 2017 Oct 2.

Laboratory of Neuroimmunology, IRCCS C. Mondino National Neurological Institute, Pavia, Italy/Department of General Neurology, IRCCS C. Mondino National Neurological Institute, Pavia, Italy.

Background: Transverse myelitis (TM) is an inflammatory disorder that can be idiopathic or associated with central nervous system autoimmune/dysimmune inflammatory diseases, connective tissue autoimmune diseases, or post-infectious neurological syndromes. Prognosis of initial TM presentations is uncertain.

Objective: To identify outcome predictors in TM.

Methods: Retrospective study on isolated TM at onset. Scores ⩾3 on the modified Rankin scale (mRS) marked high disability.

Results: A total of 159 patients were identified. TM was classified as follows: idiopathic (I-TM, n = 53), post-infectious (PI-TM, n = 48), associated with multiple sclerosis (MS-TM, n = 51), or neuromyelitis optica spectrum disorders/connective tissue autoimmune diseases/neurosarcoidosis ( n = 7). At follow-up (median, 55 months; interquartile range, 32-80), 42 patients were severely disabled, and patients with I-TM or PI-TM showed the worst outcomes. Predictors of disability were infectious antecedents, sphincter and pyramidal symptoms, high mRS scores, blood-cerebrospinal fluid barrier damage, lumbar magnetic resonance imaging (MRI) lesions on univariate analysis, and older age (odds ratio (OR), 1.1; 95% confidence interval (CI), 1.0-1.1), overt/subclinical involvement of the peripheral nervous system (PNS) (OR, 9.4; 95% CI, 2.2-41.0), complete TM (OR, 10.8; 95% CI, 3.4-34.5) on multivariate analysis.

Conclusion: Our findings help define prognosis and therapies in TM at onset. Infectious antecedents and PNS involvement associate with severe prognosis. Nerve conduction studies and lumbar MRI could improve the prognostic assessment of this condition.
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http://dx.doi.org/10.1177/1352458517731911DOI Listing
November 2018

Timing of onset affects arthritis presentation pattern in antisyntethase syndrome.

Clin Exp Rheumatol 2018 Jan-Feb;36(1):44-49. Epub 2017 Jul 26.

UOC Reumatologia, Azienda Ospedaliero Universitaria S. Anna, University of Ferrara, Italy.

Objectives: To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD).

Methods: The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2).

Results: 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005).

Conclusions: In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.
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April 2018

Assessing and treating pain in movement disorders, amyotrophic lateral sclerosis, severe acquired brain injury, disorders of consciousness, dementia, oncology and neuroinfectivology. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

Eur J Phys Rehabil Med 2016 Dec 31;52(6):841-854. Epub 2016 Aug 31.

"Cardinal Ferrari" Rehabilitation Center, Parma, Italy -

Pain is an important non-motor symptom in several neurological diseases, such as Parkinson's disease, cervical dystonia, amyotrophic lateral sclerosis, severe acquired brain injury, disorders of consciousness and dementia, as well as in oncology and neuroinfectivology. To overcome the lack of evidence-based data on pain management in these diseases, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) has defined criteria for good clinical practice among Italian neurorehabilitation professionals. Here a review of the literature (PubMed, EMBASE and gray literature) on pain characteristics, treatment and impact of pain in a neurorehabilitation setting is provided. Despite the heterogeneity of data, a consensus was reached on pain management for patients with these diseases: it is an approach originating from an analysis of the available data on pain characteristics in each disease, the evolution of pain in relation to the natural course of the disease and the impact of pain on the overall process of rehabilitation. There was unanimous consensus regarding the utility of a multidisciplinary approach to pain therapy, combining the benefits of pharmacological therapy with the techniques of physiotherapy and neurorehabilitation for all the conditions considered. While some treatments could be different depending on pathology, a progressive approach to the pharmacological treatment of pain is advisable, starting with non-opioid analgesics (paracetamol) and nonsteroidal anti-inflammatory drugs as a first-line treatment, and opioid analgesics as a second-line treatment. In cases of pain secondary to spasticity, botulinum neurotoxin, and, in some cases, intrathecal baclofen infusion should be considered. Randomized controlled trials and prospective multicenter studies aimed at documenting the efficacy of pain treatment and their risk-benefit profile are recommended for these conditions.
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December 2016

Neurofascin-155 as a putative antigen in combined central and peripheral demyelination.

Neurol Neuroimmunol Neuroinflamm 2016 Aug 7;3(4):e238. Epub 2016 Jun 7.

IRCCS (A.C., E.Z., C.O., S.R., N.V., E.A., A.M., E.M., D.F.), C. Mondino National Neurological Institute, Pavia, Italy; CNRS (J.J.D., C.M.), CRN2M-UMR 7286, Aix-Marseille Université; Gui de Chauliac Hospital (G.T., C.C.D.), Montpellier University Hospital Center; CHU Amiens-Picardie (P.M.), France; IRCCS Foundation (G.P., E.S., D.P.), C. Besta Neurological Institute, Milan; and University of Pavia (E.Z., A.M.), Italy.

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http://dx.doi.org/10.1212/NXI.0000000000000238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897982PMC
August 2016

Neurological Complications Involving the Central Nervous System After Allogeneic Hematopoietic Stem Cell Transplantation During a Period of Evolution in Transplant Modalities: A Cohort Analysis.

Transplantation 2017 Mar;101(3):616-623

1 Transplant Bone Marrow Unit, Department of Hematology Oncology Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 2 Istituto Neurologico Nazionale, IRCCS "C. Mondino", Pavia, Italy. 3 Neuroscience Consortium, University of Pavia, Monza Policlinico and Pavia Mondino, Pavia, Italy; C. Mondino National Neurological Institute, Pavia, Italy. 4 Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 5 Molecular Virology Unit, Virology and Microbiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 6 Department of Hematology Oncology Diseases Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Background: Neurological complications (NC) after hematopoietic stem cell transplantation (HSCT) are rare events. The evolution of transplant procedures has resulted in improved survival and has allowed elderly patients or those with comorbidity to receive an HSCT. The risk of NC in these patients has still not been well defined. Therefore, we carried out an observational study to estimate the occurrence and identify the risks associated with NC.

Methods: The study cohort included 452 adult-allogeneic HSCT recipients, transplanted from 1997 to 2012. The median follow up was 1.3 year (0-15.7). A myeloablative regimen was used in 307 patients. Two hundred patients were grafted from matched unrelated donor (MUD), of these, 129 (64.5%) received an in vivo T-cell depletion.

Results: Out of 452 patients, 30 (6.6%) developed NC. Infections were the most frequent causes of NC (30%). Overall survival decreased in patients developing NC (P < 0.001). Univariate survival regression on the cumulative incidence of NC identified period of transplant, linear trend between 4-year periods (1997-2012) (P < 0.001), MUD (P < 0.001), and recipient's age (P = 0.034) as significant risk factors. In multivariate analysis, period of transplant (P < 0.001) and MUD (P = 0.004) remained significant independent risk factors. Matched unrelated donor recipients showed a 3.8-fold elevated risk of developing NC.

Conclusions: Analysis highlights a temporal trend of incidence of NC that progressively increased over time and confirms a strong association between donor type and risk of NC. Our observations suggest that, although relatively uncommon, NC after allo-HSCT, may become more frequent due to the improved overall survival in recent years.
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http://dx.doi.org/10.1097/TP.0000000000001257DOI Listing
March 2017

Diagnosis and therapy of acute disseminated encephalomyelitis and its variants.

Expert Rev Neurother 2016 22;16(1):83-101. Epub 2015 Dec 22.

a C. Mondino National Institute of Neurology Foundation , IRCCS , Pavia , Italy.

Acute disseminated encephalomyelitis (ADEM) is traditionally regarded as a monophasic demyelinating disorder of the central nervous system occurring in children after infection or vaccination. ADEM in children has a polysymptomatic presentation that includes encephalopathy, fever and meningeal signs. In adults, encephalopathy is less frequent and the clinical presentation is usually dominated by long tract involvement. Despite the initial clinical severity, the functional outcome is favorable in most cases. ADEM is a subgroup within the broader spectrum of postinfectious neurological syndromes (PINSs), which includes variants characterized by additional peripheral nervous system involvement, and variants characterized by a relapsing or chronic progressive course. The literature on the matter is scarce, mostly consisting of retrospective studies. The aims of this paper are to review the clinical and paraclinical profile of ADEM and its variants, to identify potential predictors of outcome, to summarize current treatment strategies and to outline research perspectives.
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http://dx.doi.org/10.1586/14737175.2015.1126510DOI Listing
April 2018
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