Female gender doubles executive dysfunction risk in ALS: a case-control study in 165 patients.

Background: Cognitive impairment, mainly characterised by executive dysfunction, occurs in about half of cases in amyotrophic lateral sclerosis (ALS). There is evidence that gender influences some clinical features of the disease, but its influence on the cognitive spectrum is unknown. Our objective was to investigate the impact of gender on cognitive profiles of patients with ALS.

Improving the knowledge of amyotrophic lateral sclerosis genetics: novel SOD1 and FUS variants.

Amyotrophic lateral sclerosis (ALS) is as an adult-onset neurodegenerative disorder involving both upper and lower motor neurons. About 5% of all cases exhibit signs of frontotemporal degeneration (FTD). We established the mutation frequency of C9ORF72, SOD1, TARDBP, and FUS genes in 307 patients with sporadic ALS, 46 patients with familial ALS (FALS), and 73 patients affected with FTD, all originating from the northeastern part of Italy.

Pilot trial of clenbuterol in spinal and bulbar muscular atrophy.

Objective: To test the efficacy and tolerability of clenbuterol in patients with spinal and bulbar muscular atrophy (SBMA).

Methods: Twenty patients with a diagnosis of SBMA were given oral clenbuterol (0.04 mg/d) for 12 months.

Androgen-dependent impairment of myogenesis in spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disease caused by expansion of a polyglutamine (polyQ) tract in the androgen receptor (AR). SBMA is triggered by the interaction between polyQ-AR and its natural ligands, testosterone and dihydrotestosterone (DHT). SBMA is characterized by the loss of lower motor neurons and skeletal muscle fasciculations, weakness, and atrophy.

Specific numerical processing impairment in ALS patients.

The present study investigated for the first time numerical processing in sporadic amyotrophic lateral sclerosis (ALS) patients. Twenty-four non-demented patients affected by probable or definite ALS and 27 healthy controls underwent cognitive assessment. Numerical abilities (Number Comprehension, Number Transcoding, Arithmetic Fact retrieval, Calculation Skills and Arithmetic Principles) and neuropsychological functions were evaluated in accordance with Strong's consensus criteria.

C9ORF72 repeat expansion in a large Italian ALS cohort: evidence of a founder effect.

A hexanucleotide repeat expansion (RE) in C9ORF72 gene was recently reported as the main cause of amyotrophic lateral sclerosis (ALS) and cases with frontotemporal dementia. We screened C9ORF72 in a large cohort of 259 familial ALS, 1275 sporadic ALS, and 862 control individuals of Italian descent. We found RE in 23.

Mutational analysis of VCP gene in familial amyotrophic lateral sclerosis.

Mutations in valosin-containing protein (VCP) gene, already known to be associated with the multisystemic disorder, inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD), have been recently found also in familial cases of amyotrophic lateral sclerosis (ALS). To further define the frequency of VCP mutations in ALS Italian population, we screened a cohort of 166 familial ALS and 14 ALS-frontotemporal dementia (FTD) individuals. We identified a previously reported synonymous mutation (c.

Parkinson-like features in ALS with predominant upper motor neuron involvement.

Owing to the frequent observation of poverty of movements, facial hypomimia and balance impairment, amyotrophic lateral sclerosis (ALS) variant with predominance of upper motor neuron involvement (UMN-ALS) is prone to be diagnosed with Parkinsonism. A clinical assessment, including the velocity-dependent stretch response test to differentiate between pyramidal and extrapyramidal stiffness; the Unified Parkinson's Disease Rating Scale and the Berg Balance Scale to assess degree of bradykinesia and postural instability; and (123)I-FP-CIT scintigraphy evaluation to investigate the nigrostriatal circuit involvement, were carried out to characterize Parkinson-like features in UMN-ALS patients. Sixteen UMN-ALS patients were included in the study.

Natural history of upper motor neuron-dominant ALS.

A new amyotrophic lateral sclerosis (ALS) category named 'UMN-dominant ALS' and defined as 'due predominantly to UMN signs but with minor electromyogram (EMG) denervation or LMN signs on examination' has been proposed. The clinical and laboratory features of 20 patients with UMN-dominant ALS are described here, their disease course is analysed longitudinally according to their disability progression, and all these parameters are compared with those of typical ALS patients. Ten women and 10 men diagnosed with UMN-dominant ALS were evaluated.

TDP-43 in skeletal muscle of patients affected with amyotrophic lateral sclerosis.

TAR DNA binding protein (TDP-43) is the pathologic substrate of neuronal and glial aggregates in amyotrophic lateral sclerosis (ALS). Pathologic TDP-43 is hyperphosphorylated and cleaved to generate abnormal protein species that accumulate in the cytoplasm. To assess the hypothesis of TDP-43 pathology as a systemic disorder in ALS we analysed the immunohistochemical and biochemical profile of TDP-43 in muscle biopsies of 30 ALS patients and 30 controls.

Muscle histopathology in upper motor neuron-dominant amyotrophic lateral sclerosis.

The distinction between primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) still remains debated. Recently, PLS patients displaying lower motor neuron (LMN) signs have been defined as 'upper motor neuron (UMN)-dominant ALS', using 'clinically pure PLS' diagnosis to those with no LMN signs. To further characterize the LMN involvement in UMN-dominant ALS we investigated the presence and the extent of neurogenic abnormalities in the skeletal muscle of patients affected with a pyramidal syndrome consistent with UMN-dominant ALS.

Spinal and bulbar muscular atrophy: skeletal muscle pathology in male patients and heterozygous females.

Spinal and bulbar muscular atrophy (SBMA) is an adult form of X-linked motor neuron disease caused by an expansion of a CAG repeat sequence in the first exon of the androgen receptor (AR) gene. Nuclear accumulation of mutant AR with expanded polyglutamines in motor neurons is a major pathogenic mechanism. To characterize muscle involvement in SBMA the skeletal muscle biopsies of 8 SBMA patients and 3 female carriers were studied.