Alessandra Del Grande

Sacred Heart University, Fairfield, Connecticut, United States

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Publications (34)93.56 Total impact

  • European neurology. 11/2014; 73(1-2):89.
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    ABSTRACT: IgM-related neuropathy generally presents as a late-onset demyelinating polyneuropathy with predominant sensory loss and ataxia. However, we recently reported the clinical, neurophysiological and pathological findings from our cohort and identified in about a third of patients an atypical phenotype. We analyzed by flow cytometry the different lymphocytes subsets in the peripheral blood of patients affected by IgM-related neuropathy, chronic inflammatory demyelinating polyneuropathy (CIDP), monoclonal gammopathy of undetermined significance and healthy subjects, to investigate whether different immunological patterns may differentiate the classical phenotype from atypical forms. IFN-gamma producing CD4+ and CD8+ T lymphocytes, as well as CD4+ and CD8+ T cells expressing T-bet (T-helper type 1, Th1) were increased in CIDP patients. The percentage of circulating CD4+ and CD8+ T cells producing IL-10 as well as the percentage of CD19+ cells expressing Blimp-1 were higher in patients with IgM-neuropathy. We did not find any significant differences in the different lymphocytes subsets in the IgM-related neuropathy between patients with classical and atypical phenotype. Th1 cells are increased in CIDP patients while a T helper type 2-phenotype seems to prevail in patients with IgM-neuropathy. Further studies involving a larger patient population are needed to evaluate if different lymphocytes subset may be involved in different clinical phenotypes of IgM-related neuropathy.
    09/2014;
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    ABSTRACT: Introduction: Primary lymphomas of peripheral nerves are extremely rare, and only a few cases have been reported.Methods: We describe the clinical, neurophysiological, radiological, and pathological findings of a 61-year-old woman affected by primary multifocal lymphoma of the peripheral nervous system without systemic involvement.Results: Fascicular left femoral nerve biopsy was decisive for the diagnosis of diffuse large B-cell non-Hodgkin lymphoma. Magnetic resonance imaging, fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography, and nerve ultrasound contributed to the diagnosis.Conclusions: Primary lymphoma of peripheral nerves (PLPNs) is a rare but potentially treatable condition, which is frequently misdiagnosed. In the literature, there are very few descriptions of PLPNs, mostly mononeuropathies. The possibility of a neuropathy associated with lymphoma should be considered in patients with poor response to treatment and severe pain symptoms. © 2014 Wiley Periodicals, Inc.
    Muscle & Nerve 08/2014; · 2.31 Impact Factor
  • Journal of the neurological sciences. 07/2014;
  • 05/2014;
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    ABSTRACT: Introduction: Familial amyloid polyneuropathy is a rare condition caused by mutations of the transthyretin (TTR) gene. We assessed the pattern of nerve ultrasound (US) abnormalities in patients with TTR-related neuropathy. Methods: Seven patients with TTR-related neuropathy (TTR-N) and 5 asymptomatic TTR-mutation carriers (TTR-C) underwent neurological examination, nerve conduction studies, and US evaluation. Results: Multifocal US abnormalities were identified in 6/7 TTR-N. A single patient with only a mild sensory polyneuropathy had normal nerves on US evaluation. In the TTR-C we only detected an enlarged ulnar nerve at the elbow. Interestingly, disease severity correlated with number of nerves affected on US evaluation. Discussion: No specific pattern of US abnormalities was identified in this cohort. However, in TTR-related amyloid neuropathy, US may be a helpful tool in monitoring disease progression, and/or clinical response to pharmacological treatment. © 2013 Wiley Periodicals, Inc.
    Muscle & Nerve 01/2014; · 2.31 Impact Factor
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    ABSTRACT: Background Classic clinical manifestations of HNPP are characterized by recurrent painless mononeuropathies, but a minority of patients presents with atypical clinical pattern, including CMT-like neuropathy, acute or chronic inflammatory demyelinating neuropathy-like polyneuropathy, carpal tunnel syndrome. Electrophysiological examination plays a central role in the diagnosis of HNPP, disclosing a non-uniform conduction slowing, more pronounced at entrapment sites. Patients and Methods We report clinical, electrophysiological and pathological findings from 73 patients with HNPP, coming from 53 unrelated families, followed in our Institute of Neurology over a 20-year period. Results Typical presentation with recurrent multiple mononeuropathies was observed in 28/64 (44%) patients. In the remaining 36/64 (56%), we observed an atypical clinical presentation, characterized by generalized weakness and cramps; chronic ulnar neuropathy; carpal tunnel syndrome; chronic sensory polyneuropathy; Guillain-Barrè-like presentation; CMT-like presentation. Nine patients were asymptomatic for neuropathic symptoms. Nerve conduction studies showed in all cases a sensori-motor demyelinating polyneuropathy with conduction abnormalities preferentially localized at common entrapment sites. When performed, sural nerve biopsy disclosed focal thickenings of the myelin sheath in all patients. Conclusions About half of patients with HNPP from our cohort showed an atypical clinical presentation. Neurophysiological examination represents the main tool for a proper diagnosis.
    Journal of the neurological sciences 01/2014; · 2.32 Impact Factor
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    ABSTRACT: Objective: to determine the prevalence of Restless leg syndrome (RLS) in a cohort of patients with demyelinating neuropathies. Methods: patients were retrospectively recruited from our cohort of different forms of demyelinating neuropathies, including chronic inflammatory demyelinating neuropathy (CIDP), Charcot-Marie-Tooth 1A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) referred to our Department of Neurology in a ten years period. The validated four-item RLS criteria was used for diagnosis of RLS. All patients with RLS that fulfilled criteria underwent a suggested immobilization test to confirm the diagnosis. A group of out-patients referring to the sleep disorders unit and the literature data were used as controls. Results: prevalence of RLS in demyelinating neuropathy group resulted higher than prevalence observed in control population (p = 0.0142) or in the literature data (p= 0.0007). In particular, in both comparison with control population and literature data, prevalence of RLS resulted higher in CIDP group (p= 0.0266 and p=0.0063, respectively) and in CMT1A group (p= 0.0312 and p=0.0105, respectively) but not in HNPP (p = 1.000 and p = 0.9320, respectively). Conclusions: our study confirms a high prevalence of RLS in inflammatory neuropathies as CIDP and, among inherited neuropathies, in CMT1A but not in HNPP. Considering that this is only a small cohort from a single-centre, retrospective experience, the link between RLS and neuropathy remains uncertain, and larger multicentre studies are probably needed to clarify the real meaning of the association between RLS and neuropathy.
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    ABSTRACT: to determine the prevalence of restless legs syndrome (RLS) in a cohort of patients with demyelinating neuropathies. Patients were retrospectively recruited from our cohort of different forms of demyelinating neuropathies, including chronic inflammatory demyelinating neuropathy (CIDP), Charcot-Marie-Tooth 1A (CMT1A), and hereditary neuropathy with liability to pressure palsies (HNPP) referred to our Department of Neurology in a 10-year period. The validated 4-item RLS questionnaire was used for diagnosis of RLS. All patients with RLS who fulfilled criteria underwent a suggested immobilization test to confirm the diagnosis. A group of outpatients referred to the sleep disorders unit and data from published literature were used as controls. Prevalence of RLS in demyelinating neuropathy group was higher than prevalence observed in control population (p = 0.0142) or in the literature data (p = 0.0007). In particular, in comparison with both control population and literature data, prevalence of RLS was higher in CIDP group (p = 0.0266 and p = 0.0063, respectively) and in CMT1A group (p = 0.0312 and p = 0.0105, respectively), but not in HNPP (p = 1.000 and p = 0.9320, respectively). our study confirms a high prevalence of RLS in inflammatory neuropathies as CIDP and, among inherited neuropathies, in CMT1A but not in HNPP. Considering that this is only a small cohort from a single-center retrospective experience, the link between RLS and neuropathy remains uncertain, and larger multicenter studies are probably needed to clarify the real meaning of the association between RLS and neuropathy. Luigetti M; Del Grande A; Testani E; Bisogni G; Losurdo A; Giannantoni NM; Mazza S; Sabatelli M; Della Marca G. Restless leg syndrome in different types of demyelinating neuropathies: a single-center pilot study. J Clin Sleep Med 2013;9(9):945-949.
    Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 09/2013; 9(9):945-9. · 2.93 Impact Factor
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    ABSTRACT: Subacute cerebellar degeneration associated with metabotropic glutamate receptor type 1 (mGluR1) autoantibodies is an uncommon syndrome known to be part of the spectrum of paraneoplastic cerebellar degenerations associated with neuronal autoantibodies. We describe a patient with prostate adenocarcinoma who developed a subacute cerebellar ataxia. Autoantibodies specific to mGluR1 were detected in patient's serum and cerebrospinal fluid (CSF). Immunohistochemistry analyses of patient's prostate adenocarcinoma revealed abundant mGluR1 expression in luminal acinar epithelial cells and binding of patient's IgGs to tumoral mGluR1. These findings suggest that cerebellar degeneration associated with mGluR1 antibodies can be a paraneoplastic accompaniment of prostate adenocarcinoma.
    Journal of neuroimmunology 08/2013; · 2.84 Impact Factor
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    ABSTRACT: Mutations in the gene encoding FUS have been identified in a subset of patients with sporadic and familial Amyotrophic Lateral Sclerosis (ALS). Variants in the 3' Untranslated Region (3'UTR) of FUS have also been reported in ALS patients, but their pathogenic role has not been assessed.We sequenced the whole 3'UTR of FUS in 420 ALS patients who were negative for mutations in the currently known ALS genes and in 480 ethnically matched controls. We detected four 3'UTR variants (c.*48 G>A, c.*59 G>A, c.*108 C>T and c.*110 G>A) in four sporadic and in one familial ALS patients compared to none in controls (p=0.02).We investigated whether these variants impaired FUS expression in primary fibroblast cultures from three patients harbouring the c.*59 G>A, c.*108 C>T and c.*110 G>A variants, respectively. The pattern of FUS expression was also investigated in fibroblasts from one ALS patient with FUS R521C mutation, in two ALS patients without mutations in the known ALS genes and in four control individuals. By immunostaining and immunoblotting, large amounts of FUS were observed in both the cytoplasm and nuclei of mutant 3'UTR FUS fibroblasts. In FUS R521C mutant fibroblasts we observed a slight increase of FUS in the cytoplasm associated with a remarkable loss of detection in nuclei.Our findings show that mutations in 3'UTR of FUS are overrepresented in ALS patients and result into translation de-regulation of FUS. Overexpression and mislocalization of wild type FUS likely contribute to ALS pathogenesis in these cases.
    Human Molecular Genetics 07/2013; · 7.69 Impact Factor
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    ABSTRACT: Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels widely expressed throughout the mammalian brain, including bulbar and spinal motor neurons. They are involved in neuroprotection and in control of release of many neurotransmitters, including glutamate. Previous data raised the hypothesis that rare variants in the region coding the intracellular loop subunits of nAChRs might represent one of several genetic risk factors for SALS. The aim of present study was to replicate the study in an independent cohort of ALS patients. We analysed 718 sporadic ALS patients from five Italian ALS centres and 1300 ethnically matched controls. We focused primarily on CHRNA4, encoding α4 subunit, since most mutations were previously detected in this gene. We observed a significant association between CHRNA4 mutations and ALS (OR 2.91; 95% CI 1.4080-6.0453; p = 0.0056). Most mutations detected in patients were not present in the dbSNP134 and in 3500 ethnically matched control chromosomes and affected evolutionary conserved amino acid residues. In conclusion, the present data confirm that CHRNA4 variants are overrepresented in SALS strengthening the hypothesis can they act as predisposing genetic factors for SALS.
    Amyotrophic Lateral Sclerosis 08/2012; 13(6):580-4. · 3.40 Impact Factor
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    ABSTRACT: OBJECTIVE: To classify familial amyotrophic lateral sclerosis (FALS) on the base of family history, and to determine whether frequency of mutations in major amyotrophic lateral sclerosis (ALS) genes varies in different FALS categories. METHODS: Included in the study are 53 FALS families. Patients were classified as definite, probable and possible FALS, according to recently proposed criteria. Seven ALS-associated genes, including SOD1, TARDBP, FUS, ANG, ATXN2, OPTN and C9ORF72, were analysed. RESULTS: Thirteen patients (24.5%) were included in the definite group. The great majority of our FALS cases (40/53, 75.5%) were families with only two affected relatives; of these, 31 (58.5%) were included in the probable, and 9 (17%) in the possible FALS categories. The percentage of mutations was 61.5% in definite, 41.9% in probable and 11.1% in possible FALS. With respect to probable FALS, if cases with parent-to-child transmission of the disease were considered separately, the mutational load increased to 61.5%, as observed in definite FALS. CONCLUSIONS: Our findings provide evidence that frequency of mutations in currently known ALS genes varies widely among different FALS categories. Families with only two affected relatives have heterogeneous genetic components, the chance to detect mutations being higher in cases with parent-to-child transmission.
    Journal of neurology, neurosurgery, and psychiatry 07/2012; · 4.87 Impact Factor
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    ABSTRACT: To quantify the overall contribution of mutations in the currently known amyotrophic lateral sclerosis (ALS) genes in a large cohort of sporadic patients and to make genotype-phenotype correlations. Screening for SOD1, TARDBP, FUS, ANG, ATXN2, OPTN, and C9ORF72 was carried out in 480 consecutive patients with sporadic ALS (SALS) and in 48 familial ALS (FALS) index patients admitted to a single Italian referral center. Mutations were detected in 53 patients, with a cumulative frequency of 11. Seven of them were novel. The highest frequencies of positive cases were obtained in TARDBP (2.7%), C9ORF72 (2.5%), and SOD1 (2.1%). The overall group of mutated patients was indistinguishable from that without mutations as no significant differences were observed with regard to age and site of onset, frequency of clinical phenotypes, and survival. However, by separately evaluating genotype-phenotype correlation in single genes, clinical differences were observed among different genes. Duration of disease was significantly shorter in patients harboring the C9ORF72 expansion and longer in the SOD1 group. A high frequency of predominant upper motor neuron phenotype was observed among patients with TARDBP mutations. Two patients, 1 with C9ORF72 and 1 with SOD1 mutation, had concurrent ANG mutations. Mutations were detected in 43.7% of patients with FALS. A considerable proportion of patients with SALS harbored mutations in major ALS genes. This result has relevant implications in clinical practice, namely in genetic counseling. The detection of double mutations in 2 patients raises the hypothesis that multiple mutations model may explain genetic architecture of SALS.
    Neurology 06/2012; 79(1):66-72. · 8.30 Impact Factor
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    ABSTRACT: IgM-related neuropathy generally presents as a late-onset demyelinating polyneuropathy with predominant sensory loss and ataxia. Sporadic cases with atypical presentation have been described. We report clinical and pathological findings from 31 patients with IgM-related neuropathy followed in our Institute of Neurology over a 20-year period. Typical presentation with predominant sensory ataxic neuropathy was observed in 18/31 patients. In the remaining 13/31 (42%), we observed an atypical phenotype, characterized by multiple mononeuropathy or polyneuropathy with predominant motor impairment; one patient had polyneuropathy with predominant small-fibre involvement. Uncommon pathological findings consisting in inflammatory infiltrates, focal axonal loss or light chain deposition were observed in 8 patients, all with atypical clinical phenotype. Almost all patients with atypical phenotype improved with immunosuppressive therapy. A significant proportion of patients with IgM-related neuropathy presents with atypical clinical features. In these patients, sural nerve biopsy helps clarify heterogeneous disease mechanisms and identify patients who might benefit from immunosuppressive therapy.
    Journal of the neurological sciences 05/2012; 319(1-2):75-80. · 2.32 Impact Factor
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    ABSTRACT: Familial amyloid polyneuropathy (FAP) is a rare condition caused by mutations of the transthyretin (TTR) gene and it is generally characterized by a length-dependent polyneuropathy affecting prevalently the small fibers. We reviewed clinical, electrophysiological and pathological findings of 15 unrelated patients with genetically confirmed TTR-FAP. All patients presented a progressive sensory-motor polyneuropathy. Pathological findings were negative for amyloid deposits in about half of the cases. Sequence analysis of TTR gene revealed the presence of three different mutations (p.Val30Met, p.Phe64Leu, and p.Ala120Ser). The p.Val30Met was the most frequently identified mutation and it often occurred in apparently sporadic cases. Conversely, the p.Phe64Leu generally presented in a high percentage of familial cases in patients coming from Southern Italy. Clinicians should consider, to avoid misdiagnosis, the screening for TTR mutations in patients presenting with progressive axonal polyneuropathy of undetermined etiology, including apparently sporadic cases with pathological examinations negative for amyloid deposition.
    Neurological Sciences 05/2012; · 1.41 Impact Factor
  • Amyotrophic Lateral Sclerosis 02/2012; 13(2):241-2. · 3.40 Impact Factor
  • Clinical neurology and neurosurgery 12/2011; 114(6):748-50. · 1.30 Impact Factor
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of upper and lower motor neurons. Sensory involvement is thought not to be a feature of ALS. We reviewed 17 cases of sural nerve biopsies performed in a large cohort of ALS patients referred to our centre over a 23-year period. More than two-third of biopsies revealed a variable degree of axonal loss. In one case, pathological findings suggested the concomitant presence of an inherited neuropathy, subsequently confirmed by genetic evaluation. In another case, pathological and neurographic data were similar to those of an inflammatory demyelinating neuropathy, but the clinical course corroborated the diagnosis of ALS. Our data confirm that sensory nerve involvement may be found in ALS patients. This finding should prompt physicians to carefully investigate a possible alternative diagnosis, but does not exclude the possibility that the patient may have ALS.
    Neurological Sciences 12/2011; 33(5):1095-9. · 1.41 Impact Factor
  • Muscle & Nerve 10/2011; 44(4):613-5. · 2.31 Impact Factor

Publication Stats

130 Citations
93.56 Total Impact Points

Institutions

  • 2014
    • Sacred Heart University
      Fairfield, Connecticut, United States
  • 2009–2014
    • Catholic University of the Sacred Heart
      • • School of Geriatrics
      • • Institute of Neurology
      Milano, Lombardy, Italy
  • 2009–2011
    • The Catholic University of America
      Washington, Washington, D.C., United States