Novel histotypes of sporadic Creutzfeldt-Jakob disease linked to 129MV genotype.

The MV1 and MV2 subtypes of sporadic Creutzfeldt-Jakob disease (sCJD) are linked to the heterozygous methionine (M)/valine (V) polymorphism at codon 129 of the prion protein (PrP) gene. MV2 is phenotypically heterogeneous, whereas MV1, due to its low prevalence, is one of the least well characterized subtypes. In this study, we investigated the biochemical properties of PrP and phenotypic expression of cases diagnosed as sCJD MV1 and MV2.

Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence.

Background And Objectives: alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events.

Methods: lymphocyte subset counts were assessed longitudinally using linear mixed models.

Pathological 25 kDa C-Terminal Fragments of TDP-43 Are Present in Lymphoblastoid Cell Lines and Extracellular Vesicles from Patients Affected by Frontotemporal Lobar Degeneration and Neuronal Ceroidolipofuscinosis Carrying a Mutation.

Frontotemporal lobar degeneration (FTLD) is a complex disease, characterized by progressive degeneration of frontal and temporal lobes. Mutations in progranulin () gene have been found in up to 50% of patients with familial FTLD. Abnormal deposits of post-translationally-modified TAR DNA-binding protein of 43 kDa (TDP-43) represent one of the main hallmarks of the brain pathology.

Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in and Sporadic Frontotemporal Lobar Degeneration.

Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological expansion carriers, 45 heterozygous/homozygous mutation carriers, and 43 controls).

Plasma Small Extracellular Vesicles with Complement Alterations in / and Sporadic Frontotemporal Lobar Degeneration.

Cutting-edge research suggests endosomal/immune dysregulation in /-associated frontotemporal lobar degeneration (FTLD). In this retrospective study, we investigated plasma small extracellular vesicles (sEVs) and complement proteins in 172 subjects (40 Sporadic FTLD, 40 Intermediate/Pathological expansion carriers, and 49 Heterozygous/Homozygous mutation carriers, 43 controls). Plasma sEVs (concentration, size) were analyzed by nanoparticle tracking analysis; plasma and sEVs C1q, C4, C3 proteins were quantified by multiplex assay.

Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion.

Genetic prion disease accounts for 10-15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt-Jakob disease in asymptomatic carriers.

"Borderline" idiopathic CD4 T-cell lymphocytopenia presenting with atypical progressive multifocal leukoencephalopathy.

Idiopathic CD4+ lymphocytopenia (ICL) is a rare disorder characterized by low counts of CD4+ cells (<300/mm) in absence of other known causes of immunosuppression. A few cases of progressive multifocal leukoencephalopathy (PML) were reported in association with ICL with variable outcome. We describe the case of a 40 year-old man diagnosed with PML, which showed a monophasic course.

The Rise of the GRN C157KfsX97 Mutation in Southern Italy: Going Back to the Fall of the Western Roman Empire.

Background: Frontotemporal lobar degeneration (FTLD) designates a group of neurodegenerative diseases with remarkable clinical, pathological, and genetic heterogeneity. Mutations in progranulin gene (GRN) are among the most common causes of familial FTLD. The GRN C157KfsX97 mutation is the most frequent mutation occurring in Southern Italy and has been already described in a previous work.

Singular cases of Alzheimer's disease disclose new and old genetic "acquaintances".

Background: Alzheimer's disease (AD) is the most common age-related dementia. Besides its typical presentation with amnestic syndrome at onset, atypical AD cases are being increasingly recognized, often in presenile age.

Objectives: To provide an extensive clinical and genetic characterization of six AD patients carrying one or more singular features, including age of onset, atypical phenotype and disease progression rate.

Predictive factors of volumetric reduction in lumbar disc herniation treated by O2-O3 chemiodiscolysis.

Purpose: Aim of this study is to assess the effectiveness of O2-O3 percutaneous chemiodiscolysis by evaluating volumetric changes in lumbar disc herniation on magnetic resonance imaging, in order to identify possible pre-treatment factors affecting such changes Methods: Between January 2014 and December 2017, a total of 87 patients with low back pain and 103 lumbar disc herniations with MRI confirmation were considered for O2-O3 chemiodiscolysis. The volume of each herniated disc was determined before and after the treatment.

Results: Multiple linear regression analysis showed a strong correlation between post-treatment LDH volume percent change and both pre-treatment LDH volume and pre-treatment EQ-VAS (p<0.

Case Report: Histopathology and Prion Protein Molecular Properties in Inherited Prion Disease With a Seven-Octapeptide Repeat Insertion.

The insertion of additional 168 base pair containing seven octapeptide repeats in the prion protein (PrP) gene region spanning residues 51-91 is associated with inherited prion disease. In 2008, we reported the clinical features of a novel seven-octapeptide repeat insertion (7-OPRI) mutation coupled with codon 129 methionine (M) homozygosity in the PrP gene of a 19-year-old man presenting with psychosis and atypical dementia, and 16-year survival. Here, we describe the histopathological and PrP molecular properties in the autopsied brain of this patient.

A novel mechanism of phenotypic heterogeneity in Creutzfeldt-Jakob disease.

One of remarkable features of sporadic Creutzfeldt-Jakob disease (sCJD) is the great phenotypic variability. Understanding the molecular basis of this variability has important implications for the development of therapeutic approaches. It is well established that, in many cases, phenotypic heterogeneity of sCJD is under control of two determinants: the genotype at the methionine (M)/valine (V) polymorphic codon 129 of the human prion protein gene and the type, 1 or 2, of the pathogenic and disease-related form of the prion protein, PrP.

Expanding the spectrum of SPTLC1-related disorders beyond hereditary sensory and autonomic neuropathies: A novel case of the distinct "S331 syndrome".

Hereditary sensory and autonomic neuropathies (HSAN) encompass a group of peripheral nervous system disorders characterized by remarkable heterogeneity from a clinical and genetic point of view. Mutations in SPTLC1 gene are responsible for HSAN type IA, which usually starts from the second to fourth decade with axonal neuropathy, sensory loss, painless distal ulcerations, and mild autonomic features, while motor involvement usually occur later as disease progresses. Beyond the classic presentation of HSAN type IA, an exceedingly rare distinct phenotype related to SPTLC1 mutations at residue serine 331 (S331) has recently been reported, characterized by earlier onset, prominent muscular atrophy, growth retardation, oculo-skeletal abnormalities, and possible respiratory complications.

Atypical progressive multifocal leukoencephalopathy in a kidney transplant recipient with improving symptoms after immunocompetence recovery.

Progressive multifocal leukoencephalopathy (PML) is a viral infection due to John Cunningham Virus (JCV) resulting in progressive damage of brain white matter, mostly related to HIV infection or hemato-oncological malignancies. PML onset is usually multifocal with rapid neurological progression and poor prognosis. Here we report an atypical case of PML with monofocal onset and a good outcome in a 64-year-old man who received a kidney transplant for end-stage renal disease (ESRD).

Co-existence of PrP types 1 and 2 in sporadic Creutzfeldt-Jakob disease of the VV subgroup: phenotypic and prion protein characteristics.

We report a detailed study of a cohort of sporadic Creutzfeldt-Jakob disease (sCJD) VV1-2 type-mixed cases (valine homozygosity at codon 129 of the prion protein, PrP, gene harboring disease-related PrP, PrP, types 1 and 2). Overall, sCJDVV1-2 subjects showed mixed clinical and histopathological features, which often correlated with the relative amounts of the corresponding PrP type. However, type-specific phenotypic characteristics were only detected when the amount of the corresponding PrP type exceeded 20-25%.

Unusual CLIPPERS presentation and role of MRI examination in the proper diagnostic assessment: A case report.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids syndrome (CLIPPERS) is a newly described, underestimated CNS inflammatory disorder involving predominantly the midbrain and the cerebellum. CLIPPERS pathogenesis is largely unknown, and its clinical manifestations are polymorphic and sometimes confounding. Recently clinical, radiological and pathological diagnostic criteria have been proposed to discriminate CLIPPERS from potential mimickers, but the diagnosis still remains challenging.

A cluster of progranulin C157KfsX97 mutations in Southern Italy: clinical characterization and genetic correlations.

Frontotemporal lobar degeneration (FTLD) is a group of neurodegenerative diseases displaying high clinical, pathologic, and genetic heterogeneity. Several autosomal dominant progranulin (GRN) mutations have been reported, accounting for 5%-10% of FTLD cases worldwide. In this study, we described the clinical characteristics of 7 Italian patients, 5 with a diagnosis of frontotemporal dementia behavioral variant and 2 of corticobasal syndrome (CBS), carrying the GRN deletion g.

Human prion diseases: surgical lessons learned from iatrogenic prion transmission.

The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions.