Publications by authors named "Daniele Velardo"

17 Publications

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Anti-HMGCR myopathy misdiagnosed as motor neuron disease and complicated with COVID-19 infection.

Neurol Sci 2021 Mar 1. Epub 2021 Mar 1.

Neurorehabilitation Unit, NeMO Clinical Center, University of Milano, Piazza Ospedale Maggiore 3, 20162, Milano, Italy.

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http://dx.doi.org/10.1007/s10072-021-05146-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917165PMC
March 2021

Immunosuppression-related neurological disorders in kidney transplantation.

J Nephrol 2021 Jan 22. Epub 2021 Jan 22.

, Milano, Italy.

A large number of neurological disorders can affect renal transplant recipients, potentially leading to disabling or life-threatening complications. Prevention, early diagnosis and appropriate management of these conditions are critical to avoid irreversible lesions. A pivotal role in the pathogenesis of common post-transplant neurological disorders is played by immunosuppressive therapy. The most frequently administered regimen consists of triple immunosuppression, which comprises a calcineurin inhibitor (CNI), a purine synthesis inhibitor and glucocorticoids. Some of these immunosuppressive drugs may lead to neurological signs and symptoms through direct neurotoxic effects, and all of them may be responsible for the development of tumors or opportunistic infections. In this review, after a brief summary of neurotoxic pathogenetic mechanisms encompassing recent advances in the field, we focus on the clinical presentation of more common and severe immunosuppression-related neurological complications, classifying them by characteristics of urgency and anatomic site. Our goal is to provide a general framework that addresses such clinical issues with a multidisciplinary approach, as these conditions require.
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http://dx.doi.org/10.1007/s40620-020-00956-1DOI Listing
January 2021

Hyperacute extensive spinal cord infarction and negative spine magnetic resonance imaging: a case report and review of the literature.

Medicine (Baltimore) 2020 Oct;99(43):e22900

Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan.

Rationale: Spinal cord infarction (SCI) accounts for only 1% to 2% of all ischemic strokes and 5% to 8% of acute myelopathies. Magnetic resonance imaging (MRI) holds a role in ruling out non-ischemic etiologies, but the diagnostic accuracy of this procedure may be low in confirming the diagnosis, even when extensive cord lesions are present. Indeed, T2 changes on MRI can develop over hours to days, thus accounting for the low sensitivity in the hyperacute setting (ie, within 6 hours from symptom onset). For these reasons, SCI remains a clinical diagnosis. Despite extensive diagnostic work-up, up to 20% to 40% of SCI cases are classified as cryptogenic. Here, we describe a case of cryptogenic longitudinally extensive transverse myelopathy due to SCI, with negative MRI and diffusion-weighted imaging at 9 hours after symptom onset.

Patient Concerns: A 51-year-old woman presented to our Emergency Department with acute severe abdominal pain, nausea, vomiting, sudden-onset of bilateral leg weakness with diffuse sensory loss, and paresthesias on the trunk and legs.

Diagnoses: On neurological examination, she showed severe paraparesis and a D6 sensory level. A 3T spinal cord MRI with gadolinium performed at 9 hours after symptom onset did not detect spinal cord alterations. Due to the persistence of a clinical picture suggestive of an acute myelopathy, a 3T MRI of the spine was repeated after 72 hours showing a hyperintense "pencil-like" signal mainly involving the grey matter from T1 to T6 on T2 sequence, mildly hypointense on T1 and with restricted diffusion.

Interventions: The patient was given salicylic acid (100 mg/d), prophylactic low-molecular-weight heparin, and began neuromotor rehabilitation.

Outcomes: Two months later, a follow-up neurological examination revealed a severe spastic paraparesis, no evident sensory level, and poor sphincteric control with distended bladder.

Lessons: Regardless of its relatively low frequency in the general population, SCI should be suspected in every patient presenting with acute and progressive myelopathic symptoms, even in the absence of vascular risk factors. Thus, a clinical presentation consistent with a potential vascular syndrome involving the spinal cord overrides an initially negative MRI and should not delay timely and appropriate management.
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http://dx.doi.org/10.1097/MD.0000000000022900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581089PMC
October 2020

Estimating the impact of COVID-19 pandemic on services provided by Italian Neuromuscular Centers: an Italian Association of Myology survey of the acute phase.

Acta Myol 2020 Jun 1;39(2):57-66. Epub 2020 Jun 1.

Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), Neuroscience Section, University of Milan, Italy.

Introduction: Since February 2020, the outbreak of COVID-19 in Italy has forced the health care system to undergo profound rearrangements in its services and facilities, especially in the worst-hit areas in Northern Italy. In this setting, inpatient and outpatient services had to rethink and reorganize their activities to meet the needs of patients during the "lockdown". The Italian Association of Myology developed a survey to estimate the impact of these changes on patients affected by neuromuscular disorders and on specialized neuromuscular centers during the acute phase of COVID-19 pandemic.

Methods: We developed an electronic survey that was sent to neuromuscular centers affiliated with the Italian Association of Myology, assessing changes in pharmacological therapies provision, outpatient clinical and instrumental services, support services (physiotherapy, nursing care, psychological support) and clinical trials.

Results: 40% of surveyed neuromuscular centers reported a reduction in outpatient visit and examinations (44.5% of centers in Northern regions; 25% of centers in Central regions; 50% of centers in Southern regions). Twenty-two% of centers postponed in-hospital administration of therapies for neuromuscular diseases (23.4% in Northern regions; 13.0% in Central regions; 20% in Southern regions). Diagnostic and support services (physiotherapy, nursing care, psychological support) were suspended in 57% of centers (66/43/44% in Northern, Central and Southern centers respectively) Overall, the most affected services were rehabilitative services and on-site outpatient visits, which were suspended in 93% of centers. Strategies adopted by neuromuscular centers to overcome these changes included maintaining urgent on-site visits, addressing patients to available services and promoting remote contact and telemedicine.

Conclusions: Overall, COVID-19 pandemic resulted in a significant disruption of clinical and support services for patients with neuromuscular diseases. Despite the efforts to provide telemedicine consults to patients, this option could be promoted and improved further. A close collaboration between the different neuromuscular centers and service providers as well as further implementation of telehealth platforms are necessary to ensure quality care to NMD patients in the near future and in case of recurrent pandemic waves.
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http://dx.doi.org/10.36185/2532-1900-008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460733PMC
June 2020

Pediatric anti-HMGCR necrotizing myopathy: diagnostic challenges and literature review.

Neurol Sci 2020 Oct 1;41(10):3009-3013. Epub 2020 Jun 1.

Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.

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http://dx.doi.org/10.1007/s10072-020-04491-6DOI Listing
October 2020

Response to Dr. Wee.

Pain Med 2020 10;21(10):2604

Department of Neuroscience, University of Turin, Torino, Italy.

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http://dx.doi.org/10.1093/pm/pnaa056DOI Listing
October 2020

Nusinersen treatment and cerebrospinal fluid neurofilaments: An explorative study on Spinal Muscular Atrophy type 3 patients.

J Cell Mol Med 2020 03 7;24(5):3034-3039. Epub 2020 Feb 7.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy.

The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response.
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http://dx.doi.org/10.1111/jcmm.14939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077557PMC
March 2020

High-Dose Intravenous Immunoglobulin Is Effective in Painful Diabetic Polyneuropathy Resistant to Conventional Treatments. Results of a Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.

Pain Med 2020 03;21(3):576-585

Department of Neuroscience, University of Turin, Torino, Italy.

Objectives: The efficacy and safety of high-dose intravenous immunoglobulin (IVIG) in treatment-resistant diabetic painful polyneuropathy (DPN) were assessed.

Design: This was a randomized, double-blind, placebo-controlled, multicenter trial (EudraCT 2010-023883-42).

Setting: This trial was conducted at eight sites in Italy with a neurology specialist level of care.

Subjects: Twenty-six diabetic patients with DPN who reported baseline severity of pain >60 units (mm) on a VAS scale at enrollment and were resistant to antidepressants and antiepileptic drugs were enrolled; 23 were randomized (11 in the IVIG arm and 12 in the placebo arm). All patients completed the study and were evaluated. All patients were Caucasian, 15 were male, and 21 had a diagnosis of type II diabetes.

Methods: IVIG (0.4 g/kg/d) or placebo was given for five consecutive days. Pain intensity (visual analog scale, Neuropathic Pain Symptom Inventory) and quality of life (36-Item Short-Form Health Survey, Clinical/Patient Global Impression of Change questionnaires) assessments were performed at visits: baseline, start of therapy (one week later), end of therapy (five days later), and follow-up (four and eight weeks later).

Results: The study achieved its prespecified primary end point of ≥50% pain reduction at four weeks after IVIG, achieved in seven of 11 patients (63.6%) in the IVIG group vs zero of 12 in the placebo group (P = 0.0013). Only two adverse events were reported during the study: one patient in the treatment arm reported a mild "dermatitis psoriasiform," whereas one patient from the placebo group reported a mild "influenza."

Conclusions: Treatment with IVIG at the dose given was efficacious and safe for patients with DPN resistant to standard therapies.
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http://dx.doi.org/10.1093/pm/pnz331DOI Listing
March 2020

Herpes Simplex virus type 2 myeloradiculitis with a pure motor presentation in a liver transplant recipient.

Transpl Infect Dis 2020 Feb 1;22(1):e13236. Epub 2020 Jan 1.

Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan, Milan, Italy.

In this case report, we describe the first PCR-confirmed case of HSV2 myeloradiculitis with a purely motor presentation, occurring in a 68-year-old liver transplant recipient. The patient reported ascending weakness with no sensory nor sphincteric symptoms, thereby resembling acute demyelinating inflammatory neuropathy, or Guillain-Barré syndrome. HSV2 was detected in cerebrospinal fluid by PCR, and the patient was successfully treated with intravenous Acyclovir.
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http://dx.doi.org/10.1111/tid.13236DOI Listing
February 2020

Can Intestinal Pseudo-Obstruction Drive Recurrent Stroke-Like Episodes in Late-Onset MELAS Syndrome? A Case Report and Review of the Literature.

Front Neurol 2019 31;10:38. Epub 2019 Jan 31.

Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder that is most commonly caused by the m. 3243A>G mutation in the MT-TL1 mitochondrial DNA gene, resulting in impairment of mitochondrial energy metabolism. Although childhood is the typical age of onset, a small fraction (1-6%) of individuals manifest the disease after 40 years of age and usually have a less aggressive disease course. The clinical manifestations are variable and mainly depend on the degree of heteroplasmy in the patient's tissues and organs. They include muscle weakness, diabetes, lactic acidemia, gastrointestinal disturbances, and stroke-like episodes, which are the most commonly observed symptom. We describe the case of a 50-year-old male patient who presented with relapsing intestinal pseudo-obstruction (IPO) episodes, which led to a late diagnosis of MELAS. After diagnosis, he presented several stroke-like episodes in a short time period and developed a rapidly progressive cognitive decline, which unfortunately resulted in his death. We describe the variable clinical manifestations of MELAS syndrome in this atypical and relatively old patient, with a focus on paralytic ileus and stroke-like episodes; the first symptom may have driven the others, leading to a relentless decline. Moreover, we provide a brief revision of previous reports of IPO occurrence in MELAS patients with the m.3243A>G mutation, and we investigate its relationship with stroke-like episodes. Our findings underscore the importance of recognizing gastrointestinal disturbance to prevent neurological comorbidities.
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http://dx.doi.org/10.3389/fneur.2019.00038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365425PMC
January 2019

Expanding the central nervous system disease spectrum associated with FLNC mutation.

Muscle Nerve 2019 05 20;59(5):E33-E37. Epub 2019 Feb 20.

Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

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http://dx.doi.org/10.1002/mus.26443DOI Listing
May 2019

Central Nervous System Involvement in Common Variable Immunodeficiency: A Case of Acute Unilateral Optic Neuritis in a 26-Year-Old Italian Patient.

Front Neurol 2018 30;9:1031. Epub 2018 Nov 30.

Neurology Unit, Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.

Common Variable Immunodeficiency (CVID) is a group of heterogeneous primary immunodeficiencies sharing defective B lymphocytes maturation and dysregulated immune response and resulting in impaired immunoglobulin production. Clinical picture encompasses increased susceptibility to infections, hematologic malignancies, inflammatory, and autoimmune diseases. Neurological manifestations are uncommon and optic neuritis has been previously reported only in one case with bilateral involvement. We hereby report a case of a 26-year-old man affected by CVID undergoing regular immunoglobulin supplementation, who presented with acute unilateral demyelinating optic neuritis and lymphocytic pleocytosis in the cerebrospinal fluid. A variety of infectious, inflammatory, and neoplastic conditions were excluded and a diagnosis of clinically isolated optic neuritis was made. The patient was treated with a short course of intravenous steroids with complete recovery. Overall, this case expands our current knowledge about clinical spectrum of complications in CVID and highlights the need for further research about this complex disease.
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http://dx.doi.org/10.3389/fneur.2018.01031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284006PMC
November 2018

Multiparametric quantitative MRI assessment of thigh muscles in limb-girdle muscular dystrophy 2A and 2B.

Muscle Nerve 2018 10 22;58(4):550-558. Epub 2018 Aug 22.

NeuroMuscular Unit, Scientific Institute, IRCCS E. Medea, Bosisio Parini, Italy.

Introduction: The aim of this study was to apply quantitative MRI (qMRI) to assess structural modifications in thigh muscles of subjects with limb girdle muscular dystrophy (LGMD) 2A and 2B with long disease duration.

Methods: Eleven LGMD2A, 9 LGMD2B patients and 11 healthy controls underwent a multi-parametric 3T MRI examination of the thigh. The protocol included structural T1-weighted images, DIXON sequences for fat fraction calculation, T2 values quantification and diffusion MRI. Region of interest analysis was performed on 4 different compartments (anterior compartment, posterior compartment, gracilis, sartorius).

Results: Patients showed high levels of fat infiltration as measured by DIXON sequences. Sartorius and anterior compartment were more infiltrated in LGMD2B than LGMD2A patients. T2 values were mildly reduced in both disorders. Correlations between clinical scores and qMRI were found.

Conclusions: qMRI measures may help to quantify muscular degeneration, but careful interpretation is needed when fat infiltration is massive. Muscle Nerve 58: 550-558, 2018.
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http://dx.doi.org/10.1002/mus.26189DOI Listing
October 2018

Rituximab in refractory chronic inflammatory demyelinating polyradiculoneuropathy: report of four cases.

J Neurol 2017 May 23;264(5):1011-1014. Epub 2017 Mar 23.

Division of Neuroscience, Department of Neurology, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Via Olgettina 48, Milan, 20132, Italy.

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http://dx.doi.org/10.1007/s00415-017-8462-7DOI Listing
May 2017

Mesoangioblast delivery of miniagrin ameliorates murine model of merosin-deficient congenital muscular dystrophy type 1A.

Skelet Muscle 2015 3;5:30. Epub 2015 Sep 3.

Institute of Experimental Neurology (INSPE) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy.

Background: Merosin-deficient congenital muscular dystrophy type-1A (MDC1A) is characterized by progressive muscular dystrophy and dysmyelinating neuropathy caused by mutations of the α2 chain of laminin-211, the predominant laminin isoform of muscles and nerves. MDC1A has no available treatment so far, although preclinical studies showed amelioration of the disease by the overexpression of miniagrin (MAG). MAG reconnects orphan laminin-211 receptors to other laminin isoforms available in the extracellular matrix of MDC1A mice.

Methods: Mesoangioblasts (MABs) are vessel-associated progenitors that can form the skeletal muscle and have been shown to restore defective protein levels and motor skills in animal models of muscular dystrophies. As gene therapy in humans still presents challenging technical issues and limitations, we engineered MABs to overexpress MAG to treat MDC1A mouse models, thus combining cell to gene therapy.

Results: MABs synthesize and secrete only negligible amount of laminin-211 either in vitro or in vivo. MABs engineered to deliver MAG and injected in muscles of MDC1A mice showed amelioration of muscle histology, increased expression of laminin receptors in muscle, and attenuated deterioration of motor performances. MABs did not enter the peripheral nerves, thus did not affect the associated peripheral neuropathy.

Conclusions: Our study demonstrates the potential efficacy of combining cell with gene therapy to treat MDC1A.
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http://dx.doi.org/10.1186/s13395-015-0055-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560053PMC
September 2015

Longitudinal follow-up and muscle MRI pattern of two siblings with polyglucosan body myopathy due to glycogenin-1 mutation.

J Neurol Neurosurg Psychiatry 2016 07 22;87(7):797-800. Epub 2015 Jul 22.

Neuromuscular and Rare Disease Unit, Department of Neuroscience, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.

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http://dx.doi.org/10.1136/jnnp-2015-310553DOI Listing
July 2016

Balance exercise in patients with chronic sensory ataxic neuropathy: a pilot study.

J Peripher Nerv Syst 2014 Jun;19(2):145-51

Department of Neurology and Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Scientific Institute, Milan, Italy.

Although exercise therapy is considered part of the treatment of neuropathic patients, and somatosensory input is essential for motor learning, performance and neural plasticity, rehabilitation of patients with sensory ataxia has received little attention so far. The aim of this prospective pilot study was to explore the short- and medium-term efficacy of a 3-week intensive balance and treadmill exercise program in chronic ataxic neuropathy patients; 20 consecutive patients with leg overall disability sum score (ODSS-leg) ≥2, absent/mild motor signs, clinical and therapeutic stability ≥4 months were enrolled. Evaluations were done at baseline, at the end of treatment and at 3- and 6-month follow-up. Outcome measurements included: ODSS-leg, Berg balance scale, 6-min walk distance, and the functional independence measure (FIM) scale. The short-form-36 health status scale (SF-36) was used to measure health-related quality of life (HRQoL). ODSS-leg improved significantly compared with baseline, 3 weeks, 3 months (primary outcome), and 6 months follow-up. A significant improvement in all functional secondary outcome measurements and in some SF-36 subscales was also observed. This pilot study suggests that balance exercise is safe and well tolerated and might be effective in ameliorating disability and HRQoL in patients with chronic peripheral sensory ataxia.
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http://dx.doi.org/10.1111/jns5.12065DOI Listing
June 2014