Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy.

Objective: To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19).

Methods: In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period.

Mutations in ALDH1A3 represent a frequent cause of microphthalmia/anophthalmia in consanguineous families.

Anophthalmia or microphthalmia (A/M), characterized by absent or small eye, can be unilateral or bilateral and represent developmental anomalies due to the mutations in several genes. Recently, mutations in aldehyde dehydrogenase family 1, member A3 (ALDH1A3) also known as retinaldehyde dehydrogenase 3, have been reported to cause A/M. Here, we screened a cohort of 75 patients with A/M and showed that mutations in ALDH1A3 occurred in six families.

Gene expression profile in fibroblasts of Huntington's disease patients and controls.

Huntington's disease is an inherited disorder caused by expanded stretch of consecutive trinucleotides (cytosine-adenosine-guanine, CAG) within the first exon of the huntingtin (HTT) gene on chromosome 4 (p16.3). The mutated huntingtin (mHTT) gains toxic function, probably through mechanisms that involve aberrant interactions in several pathways, causing cytotoxicity.

Genetic bases of Progressive Supranuclear Palsy: the MAPT tau disease.

Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative syndrome characterized by supranuclear palsy, postural instability, and mild dementia. Neuropathologically, PSP is a four-repeat tauopathy, defined by the accumulation of neurofibrillary tangles and tufted astrocytes. Etiology remains elusive, but genetic background has a key-role in the disease pathogenesis.

CSF Alzheimer's disease-like pattern in corticobasal syndrome: evidence for a distinct disorder.

Background: Corticobasal syndrome (CBS) has a heterogeneous neuropathological spectrum, ranging from the classical corticobasal degeneration to Alzheimer's disease (AD). The neuropathology of CBS is still unpredictable. CSF tau/abeta ratio is a reliable marker of AD.

EEG and granular osmiophilic elements in early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is a rare genetic disorder mainly attributable to a mutation in the presenilin 1 (PSEN1) gene. Clinical profile and instrumental findings share common features with adult neuronal ceroid lipofuscinosis. We documented the clinical course in EOAD patients bearing mutations in PSEN1.

Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1, cause waardenburg anophthalmia syndrome.

Waardenburg anophthalmia syndrome, also known as microphthalmia with limb anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here we show that this disease is heterogeneous by reporting on a consanguineous family, not linked to the 10p11.

Founder effect and estimation of the age of the Progranulin Thr272fs mutation in 14 Italian pedigrees with frontotemporal lobar degeneration.

Progranulin (PGRN) mutations have been recognized to be monogenic causes of frontotemporal lobar degeneration (FTLD). PGRN Thr272fs mutation in the Italian population has been previously identified. In the present study, we evaluated the occurrence of a founder effect studying 8 polymorphic microsatellite markers flanking the PGRN gene in 14 apparently unrelated families.

The speech and language FOXP2 gene modulates the phenotype of frontotemporal lobar degeneration.

The FOXP2 gene is mutated in a severe monogenic form of speech and language deficits, but no study on the influence of genetic variations within FOXP2 in neurological disorders characterized by language impairment is available yet. In the present study, we investigated the impact of common FOXP2 polymorphisms with regard to frontotemporal lobar degeneration (FTLD). Two-hundred ten FTLD patients underwent clinical and a wide standardized neuropsychological examination as well as brain imaging.

A combination of CSF tau ratio and midsaggital midbrain-to-pons atrophy for the early diagnosis of progressive supranuclear palsy.

Cerebrospinal fluid (CSF) tau ratio decrease (33kDa/55kDa forms) and mid-saggital midbrain-to-pons (MP) atrophy have been suggested as diagnostic markers for progressive supranuclear palsy (PSP). The usefulness of their combined evaluation has never been tested. We evaluated the CSF tau ratio and the MP atrophy as a combined marker for early identification of PSP.

Analysis of power law models for the creep of nucleus pulposus tissue.

Tissue engineering approaches are now being investigated for altering the course of intervertebral disc degeneration (IDD). Because the disease changes the mechanical properties of the load bearing tissues of the disc, viscoelastic tissue behavior is a key measure for comparing the efficacy of treatments. To investigate the basic viscoelastic behavior of nucleus pulposus tissue, tissue from the rabbit disc was tested in torsional creep.

TARDBP mutations in frontotemporal lobar degeneration: frequency, clinical features, and disease course.

The 43-kD transactive response (TAR)-DNA-binding protein (TARDBP) mutations have been demonstrated to be causative of sporadic and familial forms of amyotrophic lateral sclerosis. More recently, these mutations have been reported in cases of frontotemporal lobar degeneration (FTLD). The aim of this study was to evaluate the role of TARDBP genetic variations in a large sample of consecutive patients with FTLD.

Cerebrovascular risk factors and triggers in transient global amnesia patients with and without jugular valve incompetence: results from a sample of 243 patients.

Background/aims: Different etiologies for transient global amnesia (TGA) have been proposed, such as venous flow abnormalities, spreading depression and migraine-related mechanisms like focal ischemia. Jugular vein valve incompetence (JVI) is commonly described in TGA patients, but its contributing role in TGA pathogenesis is still unknown. We investigated the possible relationship between JVI and pathogenetic mechanisms in TGA.

VEGF haplotypes are associated with increased risk to progressive supranuclear palsy and corticobasal syndrome.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are in the spectrum of tauopathies and recognized to have a strong genetic background. It has been widely reported that MAPT tau haplotype H1 is a genetic risk factor in both conditions, but no other genetic determinants have so far been proposed. Recently, vascular endothelial growth factor (VEGF) haplotypes were reported to confer risk to frontotemporal dementia (FTD).

Understanding the underpinnings of the frontotemporal lobar degeneration: evidence for benign and malignant forms.

Background: Frontotemporal lobar degeneration (FTLD) encompasses different clinical subtypes but with overlapping features. Establishing whether FTLD represents a continuum or recognizes distinct subgroups may be crucial for diagnostic purposes and therapeutic approaches.

Objective: To investigate whether cognitive profiles in a large sample of FTLD patients reflect qualitatively distinct subtypes, variants along a single continuum of severity, or severity differences within subtypes.

The FTLD-modified Clinical Dementia Rating scale is a reliable tool for defining disease severity in frontotemporal lobar degeneration: evidence from a brain SPECT study.

Background: Frontotemporal Lobar Degeneration (FTLD) is a heterogeneous disorder characterized by impairment in executive functions, behavioural disturbance and language deficit. Reliable scales of global impairment are under evaluation. A consortium of Mayo Clinic and University of California FTLD Centers has recently developed the FTLD-modified Clinical Dementia Rating (CDR) scale to assess FTLD severity.

Blood cell markers in Alzheimer Disease: Amyloid Precursor Protein form ratio in platelets.

A correct clinical diagnosis in the early stage of Alzheimer Disease (AD) is mandatory given the current available treatment with acetylcholine esterase inhibitors. Moreover, a early to preclinical diagnosis would allow to identify patients eligible for future disease-modifying therapies. In the last ten years, we have focused our attention on peripheral markers, evaluating the role of platelet Amyloid Precursor Protein (APP) forms as a reliable tool for AD diagnosis since preclinical stages.

Revisiting brain reserve hypothesis in frontotemporal dementia: evidence from a brain perfusion study.

Background: Literature data on Alzheimer's disease suggest that years of schooling and occupational level are associated with a reserve mechanism. No data on patients with behavioral variant frontotemporal dementia (bvFTD) are available yet.

Objective: To evaluate the impact of education, occupation, and midlife leisure activities on brain reserve in bvFTD.

Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease.

It has been recently demonstrated that the 43-kDa transactive response (TAR)-DNA-binding protein (TARDBP) is the neuropathological hallmark of Frontotemporal Dementia (FTD) with ubiquitin-positive and tau-negative inclusions. Large series of FTD patients without motor neuron disease have been previously analysed, but no TARDBP mutation was identified. The aim of the present study was to evaluate whether TARDBP gene mutations may be associated with FTD.

Subcortical and deep cortical atrophy in Frontotemporal Lobar Degeneration.

Though neuroimaging, pathology and pathophysiology suggest a subcortical and deep cortical involvement in Frontotemporal Lobar Degeneration (FTLD), no studies have comprehensively assessed the associated gray matter (GM) volume changes. We measured caudate, putamen, thalamus, and amygdala GM volume using probabilistic a-priori regions of interest (ROIs) in 53 early FTLD patients (38 behavioral variant FTD [bvFTD], 9 Semantic Dementia [SD], 6 Progressive Non-Fluent Aphasia [PNFA]), and 25 age-matched healthy controls (HC). ANOVA showed significant (P<0.

Pattern of behavioral disturbances in corticobasal degeneration syndrome and progressive supranuclear palsy.

Background: A careful characterization of behavioral abnormalities in corticobasal degeneration syndrome (CBDS) and progressive supranuclear palsy (PSP) by reliable tools is still lacking. Literature data provided evidence of the usefulness of the Frontal Behavioral Inventory (FBI) to operationalize such disturbances, particularly in the frontotemporal lobar degeneration spectrum. The study aimed to evaluate the frequency and pattern of presentation of behavioral disturbances in a large sample of CBDS and PSP patients by FBI.

Survival in frontotemporal lobar degeneration and related disorders: latent class predictors and brain functional correlates.

Background: Establishing survival rate in frontotemporal lobar degeneration (FTLD) is a clinical challenge for defining disease outcomes and monitoring therapeutic interventions. Using the latent profile analysis (LPA) approach, we have previously suggested that FTLD patients can be grouped into specific phenotypes- "pseudomanic behavior" (LC1), "cognitive" (LC2), and "pseudodepressed behavior" (LC3)-on the basis of neuropsychological, functional, and behavioral data.

Objective: The aim of this study was to evaluate the rate of survival in FTLD, to identify predictors of survival, and to determine the likely usefulness of LPA in defining prognosis.

Is early-onset clinically different from late-onset frontotemporal dementia?

Background And Purpose: Frontotemporal dementia (FTD) is the second most common neurodegenerative dementia in the young age after Alzheimer disease. Recent improvement in diagnostic assessment suggests that it is more common than previously, although with a great heterogeneity in clinical presentation. The different clinical patterns related to age of disease onset in behavioural variant FTD (bvFTD) have been fairly studied.